salicylates and bismuth-subsalicylate

Budesonide is accepted as first-choice therapy for microscopic colitis (MC); however, symptoms often recur and some patients may be dependent, intolerant, or even fail budesonide. We performed a systematic review and meta-analysis to determine the effectiveness of non-budesonide therapies (thiopurines, bismuth subsalicylate [BSS], bile acid sequestrants [BAS], loperamide and biologics) for MC suggested by international guidelines.. We searched the CENTRAL, MEDLINE, and EMBASE databases from their inception to 18 April 2023 for the above-mentioned therapeutics in MC. We pooled the response and remission rates by medication using a random-effects model.. Twenty-five studies comprising 1475 patients were included in the meta-analysis. Treatment with BSS showed the highest response rate of 75% (95% confidence interval [CI] 0.65-0.83; I. PROSPERO protocol #CRD42020218649.

Topics: Budesonide; Colitis, Microscopic; Humans; Loperamide; Salicylates

A large number of studies have evaluated the pharmacology, safety, and/or efficacy of bismuth subsalicylate for the relief of common gastrointestinal symptoms, diarrhea and vomiting due to acute gastroenteritis. In addition, short-term (48 h) medication with bismuth subsalicylate is known to be effective against infectious gastroenteritis such as travelers' diarrhea.. Previous studies have documented the bacteriostatic/bactericidal effects of bismuth subsalicylate against a variety of pathogenic gastrointestinal bacteria. However, meta-analyses of the clinical efficacy of bismuth subsalicylate for both prevention and treatment of travelers' diarrhea have not yet been published.. A total of 14 clinical studies (from 1970s to 2007) comprised the core data used in this assessment of efficacy of bismuth subsalicylate against infectious (including travelers') diarrhea. These studies allowed for statistical meta-analyses regarding prevention (three travelers' diarrhea studies) and treatment of infectious diarrhea (11 studies [five travelers' diarrhea]).. The results show that subjects treated with bismuth subsalicylate for up to 21 days have 3.5 times greater odds of preventing travelers' diarrhea compared with placebo (95% CI 2.1, 5.9; p < 0.001). In addition, subjects with infectious diarrhea treated with bismuth subsalicylate had 3.7 times greater odds of diarrhea relief (recorded on diaries as subjective symptomatic improvement) compared to those receiving placebo (95% CI 2.1, 6.3; p < 0.001).. This systematic review and meta-analysis suggests that bismuth subsalicylate can be beneficial for those at risk or affected by food and waterborne diarrheal disease such as traveler's (infectious) diarrhea, and may decrease the risk of inappropriate antibiotic utilization.

Topics: Bismuth; Communicable Diseases; Diarrhea; Humans; Organometallic Compounds; Salicylates; Travel

As one of the most prevalent infections globally, Helicobacter pylori (H. pylori) continues to present diagnostic and therapeutic challenges for clinicians worldwide. Diagnostically, the "test-and-treat" strategy is the recommended approach for healthcare practitioners when managing this potentially curable disease. The choice of testing method should be based on several factors including patient age, presenting symptoms, and medication use, as well as test reliability, availability, and cost. With rising antibiotic resistance, particularly of macrolides, care must be taken to ensure that therapy is selected based on regional resistance patterns and prior antibiotic exposure. In the USA, macrolide antibiotic resistance rates in some areas have reached or exceeded a generally accepted threshold, such that clarithromycin triple therapy may no longer be an appropriate first-line empiric treatment. Instead, bismuth quadruple therapy should be considered, while levofloxacin-based or alternative macrolide-containing therapies are also options. Once treated, it is essential to test for eradication as untreated H. pylori is associated with serious complications including peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. This review article aims to consolidate current knowledge of H. pylori infection with a particular emphasis on diagnostic and treatment strategies.

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Antigens, Bacterial; Biopsy; Bismuth; Breath Tests; Clarithromycin; Culture Techniques; Doxycycline; Drug Resistance, Bacterial; Drug Therapy, Combination; Dyspepsia; Feces; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Lymphoma, B-Cell, Marginal Zone; Metronidazole; Nitro Compounds; Organometallic Compounds; Peptic Ulcer; Polymerase Chain Reaction; Proton Pump Inhibitors; Rifabutin; Salicylates; Salvage Therapy; Serologic Tests; Stomach Neoplasms; Tetracycline; Thiazoles; Treatment Outcome; Urea

Travelers' diarrhea is the most common travel-related malady. It affects millions of international travelers to developing countries annually and can significantly disrupt travel plans.. To provide an update on the evaluation, diagnosis, treatment, and prevention of traveler's diarrhea.. A PubMed search was completed in Clinical Queries using the key term "traveler's diarrhea". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. Patents were searched using the key term "traveler's diarrhea" from www.freepatentsonline.com.. Between 10% and 40% of travelers develop diarrhea. The attack rate is highest for travelers from a developed country who visit a developing country. Children are at particular risk. Travelers' diarrhea is usually acquired through ingestion of food and water contaminated by feces. Most cases are due to a bacterial pathogen, commonly, Escherichia coli, and occur within the first few days after arrival in a foreign country. Dehydration is the most common complication. Pretravel education on hygiene and on the safe selection of food items is important in minimizing episodes. For mild travelers' diarrhea, the use of antibiotic is not recommended. The use of bismuth subsalicylate or loperamide may be considered. For moderate travelers' diarrhea, antibiotics such as fluoroquinolones, azithromycin, and rifaximin may be used. Loperamide may be considered as monotherapy or adjunctive therapy. For severe travelers' diarrhea, antibiotics such as azithromycin, fluoroquinolones, and rifaximin should be used. Azithromycin can be used even for the treatment of dysentery whereas fluoroquinolones and rifaximin cannot be used for such purpose. Recent patents related to the management of travelers' diarrhea are discussed.. Although travelers' diarrhea is usually self-limited, many travelers prefer expedient relief of diarrhea, especially when they are traveling for extended periods by air or ground. Judicious use of an antimotility agent and antimicrobial therapy reduces the duration and severity of diarrhea.

Topics: Anti-Bacterial Agents; Azithromycin; Bismuth; Dehydration; Developing Countries; Dysentery; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Food Contamination; Health Knowledge, Attitudes, Practice; Humans; Loperamide; Organometallic Compounds; Patient Education as Topic; Salicylates

Lymphocytic colitis is a cause of chronic diarrhea. It is a subtype of microscopic colitis characterized by chronic, watery, non-bloody diarrhea and normal endoscopic and radiologic findings. The etiology of this disorder is unknown.Therapy is based mainly on case series and uncontrolled trials, or by extrapolation of data for treating collagenous colitis, a related disorder. This review is an update of a previously published Cochrane review.. To evaluate the efficacy and safety of treatments for clinically active lymphocytic colitis.. The MEDLINE, PUBMED and EMBASE databases were searched from inception to 11 August 2016 to identify relevant papers. Manual searches from the references of included studies and relevant review articles were performed.Abstracts from major gastroenterological meetings were also searched to identify research submitted in abstract form only. The trial registry web site www.ClinicalTrials.gov was searched to identify registered but unpublished trials. Finally, the Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register were searched for other studies.. Randomized controlled trials assessing medical therapy for patients with biopsy-proven lymphocytic colitis were considered for inclusion DATA COLLECTION AND ANALYSIS: Data was independently extracted by at least two authors. Any disagreements were resolved by consensus. Data were analyzed on an intention-to-treat (ITT) basis. The primary outcome was clinical response as defined by the included studies. Secondary outcome measures included histological response as defined by the included studies, quality of life as measured by a validated instrument and the occurrence of adverse events. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. Data were combined for analysis if they assessed the same treatments. Dichotomous data were combined using a pooled RR along with corresponding 95% CI. A fixed-effect model was used for the pooled analysis.. Five RCTs (149 participants) met the inclusion criteria. These studies assessed bismuth subsalicylate versus placebo, budesonide versus placebo, mesalazine versus mesalazine plus cholestyramine and beclometasone dipropionate versus mesalazine. The study which assessed mesalazine versus mesalazine plus cholestyramine and the study which assessed beclometasone dipropionate versus mesalazine were judged to be at high risk of bias due to lack of blinding. The study which compared bismuth subsalicylate versus us placebo was judged as low quality due to a very small sample size and limited data. The other 3 studies were judged to be at low risk of bias. Budesonide (9 mg/day for 6 to 8 weeks) was significantly more effective than placebo for induction of clinical and histological response. Clinical response was noted in 88% of budesonide patients compared to 38% of placebo patients (2 studies; 57 participants; RR 2.03, 95% CI 1.25 to 3.33; GRADE = low). Histological response was noted in 78% of budesonide patients compared to 33% of placebo patients (2 studies; 39 patients; RR 2.44, 95% CI 1.13 to 5.28; GRADE = low). Forty-one patients were enrolled in the study assessing mesalazine (2.4 g/day) versus mesalazine plus cholestyramine (4 g/day). Clinical response was noted in 85% of patients in the mesalazine group compared to 86% of patients in the mesalazine plus cholestyramine group (RR 0.99, 95% CI 0.77 to 1.28; GRADE = low). Five patients were enrolled in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks versus placebo). There were no differences in clinical (P=0.10) or histological responses (P=0.71) in patients treated with bismuth subsalicylate compared with placebo (GRADE = very low). Forty-six patients were enrolled in the trial studying beclometasone dipropionate (5 mg/day or 10 mg/day) versus mesalazine (2.4 g/day). There were no differences in clinical remission at 8 weeks (RR 0.97; 95% CI 0.75 to 1.24; GRADE = low) and 12 months of treatment (RR 1.29; 95% CI 0.40 to 4.18; GRADE = very low). Although patients receiving beclometasone dipropionate (84%) and mesalazine (86%) achieved clinical remission at 8 weeks, it was not maintained at 12 months (26% and 20%, respectively). Adverse events reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, hyperhidrosis and headache. Nausea and skin rash were reported as adverse events in the mesalazine study. Adverse events in the beclometasone dipropio. Low quality evidence suggests that budesonide may be effective for the treatment of active lymphocytic colitis. This benefit needs to be confirmed by a large placebo -controlled trial. Low quality evidence also suggests that mesalazine with or without cholestyramine and beclometasone dipropionate may be effective for the treatment of lymphocytic colitis, however this needs to be confirmed by large placebo-controlled studies. No conclusions can be made regarding bismuth subsalicylate due to the very small number of patients in the study, Further trials studying interventions for lymphocytic colitis are warranted.

Topics: Anti-Inflammatory Agents; Antidiarrheals; Beclomethasone; Bismuth; Budesonide; Cholestyramine Resin; Colitis, Lymphocytic; Humans; Mesalamine; Organometallic Compounds; Randomized Controlled Trials as Topic; Salicylates

Collagenous colitis is a cause of chronic diarrhea. This updated review was performed to identify therapies for collagenous colitis that have been assessed in randomized controlled trials (RCTs).. The primary objective was to assess the benefits and harms of treatments for collagenous colitis.. We searched CENTRAL, the Cochrane IBD Group Specialized Register, MEDLINE and EMBASE from inception to 7 November 2016.. We included RCTs comparing a therapy with placebo or active comparator for the treatment of active or quiescent collagenous colitis.. Data were independently extracted by two authors. The primary outcome was clinical response or maintenance of response as defined by the included studies. Secondary outcome measures included histological response, quality of life and the occurrence of adverse events. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The Cochrane risk of bias tool was used to assess bias. The overall quality of the evidence was assessed using the GRADE criteria.. Low quality evidence suggests that budesonide may be effective for inducing and maintaining clinical and histological response in patients with collagenous colitis. We are uncertain about the benefits and harms of therapy with bismuth subsalicylate, Boswellia serrata extract, mesalamine with or without cholestramine, prednisolone and probiotics. These agents and other therapies require further study.

Topics: Bismuth; Boswellia; Budesonide; Cholestyramine Resin; Chronic Disease; Colitis, Collagenous; Diarrhea; Glucocorticoids; Humans; Mesalamine; Organometallic Compounds; Plant Extracts; Prednisolone; Probiotics; Randomized Controlled Trials as Topic; Salicylates

Microscopic colitis is a common cause of chronic diarrhea. It is characterized by non-bloody watery diarrhea with macroscopically normal colonic mucosa. Its specific histological characteristics confirm the diagnosis. Two distinct histological forms can be identified, namely, collagenous colitis and lymphocytic colitis. In collagenous colitis, a thick colonic subepithelial collagenous deposit can be observed, whereas in lymphocytic colitis, a pronounced intraepithelial lymphocytic inflammation in the absence of a thickened collagen band can be identified. Microscopic colitis occurs more frequently in elderly females and its etiology is believed to be multifactorial, although smoking and consumption of several drugs have been identified as risks factors for the development of the disease. The treatment is based on avoiding the risks factors and administration of oral budesonide.

Topics: Anti-Inflammatory Agents; Antidiarrheals; Bismuth; Budesonide; Colitis, Microscopic; Humans; Immunosuppressive Agents; Induction Chemotherapy; Maintenance Chemotherapy; Mesalamine; Organometallic Compounds; Probiotics; Risk Factors; Salicylates; Tumor Necrosis Factor-alpha

Traveler's diarrhea (TD) is the most common travel-related illness, and it can have a significant impact on the traveler. Pretravel consultation provides an excellent opportunity for the clinician to counsel the traveler and discuss strategies such as food and water hygiene, vaccinations, and medications for prophylaxis or self-treatment that may decrease the incidence and impact of TD. Postinfectious sequelae, such as postinfectious irritable bowel syndrome, reactive arthritis, and Guillain-Barre syndrome, may develop weeks or months after return.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Antidiarrheals; Arthritis, Reactive; Bismuth; Dehydration; Diarrhea; Female; Fluid Therapy; Foodborne Diseases; Guillain-Barre Syndrome; Humans; Immunocompromised Host; Irritable Bowel Syndrome; Organometallic Compounds; Pregnancy; Probiotics; Risk Factors; Salicylates; Travel; Travel Medicine; Vaccines; Waterborne Diseases

It is estimated that approximately 30% to 70% of international travellers will develop diarrhoea during their travels or after returning home.. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 24 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (empirical), antibiotics plus antimotility agents, antimotility agents, bismuth subsalicylate, diet, oral rehydration solutions, and racecadotril for travellers' diarrhoea.

Topics: Anti-Bacterial Agents; Antidiarrheals; Bismuth; Diarrhea; Diet; Fluid Therapy; Humans; Organometallic Compounds; Salicylates; Thiorphan; Travel-Related Illness

Chronic diarrhea is a frequent and challenging problem in clinical medicine. In a considerable subgroup of these, no underlying cause is identified and this is referred to as functional diarrhea. A consensus definition for functional diarrhea is based on loose stool consistency and chronicity and absence of coexisting irritable bowel syndrome. Underlying pathophysiology includes rapid intestinal transit, which may be worsened by stress or be triggered by a preceding infectious gastroenteritis. Diagnostic work-up aims at exclusion of underlying organic disease. Treatment starts with dietary adjustments, aiming at decreasing nutrients that enhance transit and stool and at identifying precipitating food items.

Topics: Antidepressive Agents, Tricyclic; Antidiarrheals; Bismuth; Carbon; Cholestyramine Resin; Chronic Disease; Clonidine; Diarrhea; Humans; Octreotide; Organometallic Compounds; Oxides; Probiotics; Receptors, Opioid; Salicylates; Serotonin 5-HT3 Receptor Antagonists; Thiorphan

Diarrhea is a common clinical feature of inflammatory bowel diseases and may be accompanied by abdominal pain, urgency, and fecal incontinence. The pathophysiology of diarrhea in these diseases is complex, but defective absorption of salt and water by the inflamed bowel is the most important mechanism involved. In addition to inflammation secondary to the disease, diarrhea may arise from a variety of other conditions. It is important to differentiate the pathophysiologic mechanisms involved in the diarrhea in the individual patient to provide the appropriate therapy. This article reviews microscopic colitis, ulcerative colitis, and Crohn's disease, focusing on diarrhea.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antidiarrheals; Bacterial Infections; Biopsy; Bismuth; Blood Cell Count; Blood Chemical Analysis; Body Water; Breath Tests; Budesonide; Cholestyramine Resin; Colitis, Microscopic; Diarrhea; Drug-Related Side Effects and Adverse Reactions; Endoscopy, Gastrointestinal; Feces; Glucocorticoids; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Intestinal Absorption; Intestinal Fistula; Intestinal Mucosa; Intestines; Ion Transport; Malabsorption Syndromes; Medical History Taking; Mesalamine; Organometallic Compounds; Physical Examination; Postoperative Complications; Prednisolone; Salicylates; Sodium; Tumor Necrosis Factor-alpha

National Danish guidelines for the diagnosis and treatment of Helicobacter pylori (Hp) infection have been approved by the Danish Society for Gastroenterology. All patients with peptic ulcer disease, gastric cancer, and MALT lymphoma should be tested for Hp. We also recommend testing in first degree relatives to patients with gastric cancer, in NSAID-naive patients, who need long-term NSAID therapy, and in patients presenting with dyspepsia and no alarm symptoms. Non-endoscoped patients can be tested with a urea-breath test or a faecal antigen test. Endoscoped patients can be tested with a rapid urease test. Proton pump inhibitor therapy should be stopped at least 1 week prior to Hp testing. All infected patients should be offered Hp eradication therapy. First-line treatment is 7-day triple therapy with a proton pump inhibitor and clarithromycine in combination with metronidazole or amoxicilline. Quadruple therapy for 2 weeks with bismuthsubsalicylate, tetracycline, metronidazole and a proton pump inhibitor is recommended in case of treatment failure. Hp testing should be offered to all patients after eradication therapy but is mandatory in patients with ulcer disease, noninvasive gastric cancer or MALT lymphoma. Testing after eradication should not be done before 4 weeks after treatment has ended.

Topics: Amoxicillin; Anti-Bacterial Agents; Antidiarrheals; Bismuth; Clarithromycin; Denmark; Drug Therapy, Combination; Dyspepsia; Helicobacter Infections; Helicobacter pylori; Humans; Lymphoma, B-Cell, Marginal Zone; Metronidazole; Organometallic Compounds; Peptic Ulcer; Proton Pump Inhibitors; Salicylates; Stomach Neoplasms; Tetracycline

Travelers' diarrhea affects more than 10 million people per year and is usually contracted through the ingestion of microbially contaminated food or water. Although most cases resolve in 3 to 5 days, chronic conditions are associated with acute infections. Prevention encompasses avoidance of ingesting contaminated products and, in certain situations, taking prophylactic medications. The available prophylactic antibiotics are very effective in prevention, but are recommended only for specific at-risk individuals and are contraindicated for most travelers.

Topics: Antibiotic Prophylaxis; Antidiarrheals; Bismuth; Diarrhea; Disinfection; Fluid Therapy; Food Contamination; Food Microbiology; Humans; Hygiene; Organometallic Compounds; Risk Factors; Salicylates; Travel; Water Microbiology

Macular pigmentation of the tongue can be acquired following exposure to exogenous agents. Black lingual hyperpigmentation was observed during the full body skin examination of a man with a history of recurrent metastatic malignant melanoma. His tongue spontaneously returned to its normal pink color later that day. Bismuth subsalicylate (Pepto-Bismol) was suspected as the pigment-inducing agent; subsequently, re-challange with the antacid confirmed it to be the cause of his acquired, albeit transient, black tongue. The ingestion of medications, including other antacids, analgesics, antidepressants, antihypertensives and several antimicrobials has been associated with the development of acquired macular lingual pigmentation. In addition, hyperpigmentation of the tongue has been observed following the deposition of amalgam and the injection of local anesthesia or doxorubicin or interferon alpha and ribavirin. Also, inhalation of heroin and methaqualone vapors or tobacco has resulted in lingual hyperpigmentation. All of the patients with acquired macular lingual hyperpigmentation had tongues with a smooth surface without enlargement of the filiform papillae. Many of the individuals with hyperpigmented tongue had either black or dark skin color. The onset of tongue pigmentation varied from less than one day to several years after initial exposure to the associated exogenous agent. The color of the tongue usually returned to normal after the pigment-inducing agent was discontinued.

Topics: Bismuth; Humans; Hyperpigmentation; Male; Middle Aged; Organometallic Compounds; Salicylates; Tongue Diseases

Lymphocytic colitis is a cause of chronic diarrhea. Therapy is based mainly on case series and uncontrolled trials, or by extrapolation of data for treating collagenous colitis, a related disorder. This review was performed to identify therapies for lymphocytic colitis that have been proven in randomized controlled trials.. To determine effective treatments for patients with clinically active lymphocytic colitis.. The MEDLINE, PUBMED and EMBASE databases were searched using the search criteria "microscopic colitis" or "lymphocytic colitis" and "treatment" or "therapy" or "management" to identify relevant papers published between 1970 and December 2007. Manual searches from the references of identified papers and relevant review papers were performed. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. The trial registry website www.ClinicalTrials.gov was searched to identify registered but unpublished trials. Finally, the Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register were searched for other studies.. Five randomized controlled trials were identified. Three of these studies, which assessed bismuth subsalicylate vs. placebo, budesonide vs. placebo, and mesalazine vs. mesalazine vs. cholestyramine in treating active disease, are included in this review.. Data were extracted independently by each author onto 2x2 tables (treatment versus placebo or active comparator and response versus no response). For therapies assessed in one trial only, P values were derived using the chi-square test.. Forty-one patients were enrolled in the trial studying budesonide (9 mg/day for 6 weeks versus placebo). Budesonide was more effective than placebo at inducing both clinical (P = 0.004; NNT = 3) and histological responses (P = 0.04; NNT = 3). Forty-one patients were enrolled in the study assessing mesalazine versus mesalazine plus cholestyramine. A high proportion of patients in each group responded to treatment. However, no statistically significant difference in clinical response was found between the two treatment groups (P = 0.95). Five patients were enrolled in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks vs. placebo). There were no differences in clinical (P=0.10) or histological responses (P=0.71) in patients treated with bismuth subsalicylate compared with placebo.. A single trial studying budesonide suggests that it may be effective for the treatment of active lymphocytic colitis. An ongoing placebo-controlled trial may confirm the benefit of budesonide. There is weaker evidence that mesalazine with or without cholestyramine may be effective for the treatment of lymphocytic colitis, but this benefit needs to be confirmed in a placebo-controlled study. No conclusions can be made regarding bismuth subsalicylate. These agents require further study before they can be recommended as treatment options for lymphocytic colitis. Further trials studying interventions for lymphocytic colitis are warranted.

Topics: Antidiarrheals; Bismuth; Budesonide; Cholestyramine Resin; Colitis, Lymphocytic; Humans; Mesalamine; Organometallic Compounds; Randomized Controlled Trials as Topic; Salicylates

Lymphocytic colitis is a cause of chronic diarrhea. Therapy is based mainly on case series and uncontrolled trials, or by extrapolation of data for treating collagenous colitis, a related disorder. This review was performed to identify therapies for lymphocytic colitis that have been proven in randomized controlled trials.. To determine effective treatments for patients with clinically active lymphocytic colitis.. The MEDLINE, PUBMED and EMBASE databases were searched using the search criteria "microscopic colitis" or "lymphocytic colitis" and "treatment" or "therapy" or "management" to identify relevant papers published between 1970 and September 2006. Manual searches from the references of identified papers and relevant review papers were performed. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Finally, the Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register was searched for other studies.. A single randomized trial published in abstract form only which studied bismuth subsalicylate was identified, and included only 5 patients with lymphocytic colitis (and 9 with collagenous colitis).. Data were extracted independently by each author onto 2x2 tables (treatment versus placebo and response versus no response). For therapies assessed in one trial only, P values were derived using the chi-square test.. There were 5 patients with lymphocytic colitis in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks vs. placebo). Although all three patients on active drug experienced clinical improvement compared to none of the placebo group, there were no statistically significant differences in clinical (P = 0.10) or histological (P = 0.71) improvement.. A single trial studying bismuth subsalicylate as therapy for lymphocytic colitis suggests that it may be beneficial. However, it included only 5 patients and no firm conclusions can be made from such a small trial. Larger trials studying treatments for lymphocytic colitis are warranted.

Topics: Antidiarrheals; Bismuth; Colitis, Lymphocytic; Humans; Organometallic Compounds; Salicylates

Microscopic colitis is a common cause of chronic watery diarrhea. Its etiology is unknown, but use of nonsteroidal antiinflammatory drugs, aspirin, and lansoprazole may be risk factors for developing the disorder. Therapy is directed primarily at resolving the symptoms of microscopic colitis; bismuth subsalicylate, aminosalicylates, traditional corticosteroids, and budesonide have been evaluated. Compared with other therapies, budesonide has the strongest evidence for effectiveness in decreasing the volume and frequency of stools and improving the quality of life; it is, however, a costly drug. We reviewed all available primary English-language literature accounts of treatment of microscopic colitis. We performed searches of MEDLINE and International Pharmaceutical Abstracts, as well as reviewing the bibliographies from key articles, to procure pertinent reports. Microscopic colitis can be successfully treated with pharmacotherapy. Based on cost and adverse-effect profiles, antidiarrheals and bismuth subsalicylate are reasonable first options, but many patients may require budesonide to achieve remission.

Topics: Adrenal Cortex Hormones; Bismuth; Budesonide; Cholestyramine Resin; Colitis, Microscopic; Humans; Loperamide; Organometallic Compounds; Salicylates; Treatment Outcome

Along with the dizzying rise in the world's population and economic globalization, travel activity has also increased. Travelers' diarrhea, caused by changed sanitary conditions, has a very different pathogenic spectrum and clinical course from those of our native forms of infectious enterocolitis. Awareness of the warning signs of complications in the clinical course and of the differential diagnoses is therefore a prerequisite for rational therapy. This covers oral rehydration, motility inhibitors, adsorbents, antisecretory agents, probiotics, and last but not least the use of antibiotics, which make an essential contribution if correctly used. There are interesting developments in the form of nonabsorbable antibiotics and new antisecretory agents, which inhibit protein synthesis and enzymes and are increasingly used as antidiarrheal agents with few side effects. In the combination of various therapeutic options in travelers' diarrhea there is still much scope for research. The priority is the correct implementation of the options available today, in order to avoid, as far as possible, therapeutic setbacks and the development of resistance.

Topics: Adult; Anti-Bacterial Agents; Atropine; Bismuth; Child; Cross-Sectional Studies; Diphenoxylate; Drug Combinations; Dysentery; Fluid Therapy; Fluoroquinolones; Humans; Loperamide; Organometallic Compounds; Probiotics; Risk Factors; Salicylates; Travel

Travellers' diarrhoea remains a major public health problem, contributing to significant morbidity and disability. Because bacterial enteropathogens cause a majority of this form of diarrhoea, antibacterial drugs are effective when used in chemoprophylaxis or for empirical treatment.A review of the MEDLINE listings for travellers' diarrhoea for the past 4 years was conducted; a library of >1,000 scientific articles on the topic was also considered in developing this review. Persons who travel from industrialised countries to developing countries of the tropical and semi-tropical world are the individuals who experience travellers' diarrhoea. While diarrhoea occurs with reduced frequency among persons travelling to low-risk areas from other low- or other high-risk areas, and there remain areas of intermediate risk, this review looks primarily at the illness occurring in persons from industrialised regions visiting high-risk regions of Latin America, Africa and Southern Asia. The material reviewed deals with the high frequency of acquiring diarrhoea during international travel to high-risk areas, seen in approximately 40%, and the expected bacterial causes of illness, of which diarrhoeagenic Escherichia coli is the most important. The host risk factors associated with increased susceptibility to diarrhoea include young age, lack of previous travel to high-risk regions in the past 6 months, indiscriminate food and beverage selection patterns, and host genetics. It appears feasible to decrease the rate of illness among the travelling public by careful food and beverage selection or through chemoprophylaxis with nonabsorbed rifaximin. Chemoprophylaxis with rifaximin should help to reduce the occurrence of travellers' diarrhoea and hopefully prevent post-diarrhoea complications, including irritable bowel syndrome. Early empirical therapy with antibacterial drugs, including rifaximin, a fluoroquinolone or azithromycin, will decrease the duration of illness and return travellers more quickly to their planned activities.With collaboration between local governments and public health researchers, it may be possible to improve hygiene in areas to be visited, which may translate into reduced rates of illness. More liberal use of rifaximin prophylaxis is likely to reduce the occurrence of illness and complications of disease. Vaccines and immunoprophylactic products may be beneficial for prevention of a subset of individuals otherwise developing diarrhoea.

Topics: Anti-Bacterial Agents; Antidiarrheals; Azithromycin; Bismuth; Campylobacter; Clinical Trials as Topic; Diarrhea; Drug Resistance, Bacterial; Escherichia coli; Food Microbiology; Humans; Hygiene; Organometallic Compounds; Rifamycins; Rifaximin; Salicylates; Shigella; Travel; Water Microbiology

Diarrhea continues to be the leading health problem among international travelers to developing tropical and semi-tropical regions. Despite more than 50 years of research providing information about the etiology and pathogenesis of the disease, the rate of illness and consequences remain unchanged. An estimated 40% of travelers to developing nations will become ill with diarrhea. Although travelers' diarrhea is considered a self-limited disease, novel and effective approaches to disease prevention and treatment have been realized in recent years. Also, recent evidence has identified a potential for long-term complications of the illness, including postinfectious irritable bowel syndrome. With the advent of poorly absorbed (<0.4%) rifaximin, a treatment option for the common watery diarrhea syndrome equivalent to previously used absorbed antibacterial drugs has emerged. Rifaximin with an excellent safety profile and limited potential to induce coliform resistance, prevents most of the diarrhea that would otherwise occur. With further studies in different settings, new consideration should be given to the routine use of chemoprophylaxis for travelers to high-risk countries. Antibacterial drugs will continue to be the optimal treatment for travelers' diarrhea subjects for the most part caused by bacterial enteropathogens and shorten the duration of diarrhea by 1-2 days compared with no active drug treatment.

Topics: Bismuth; Diarrhea; Fluid Therapy; Humans; Organometallic Compounds; Probiotics; Rifamycins; Rifaximin; Risk Factors; Salicylates; Travel

To conduct a systematic review to determine effective treatments for patients with clinically active collagenous colitis.. Relevant articles were identified via the MEDLINE, PUBMED, and Cochrane Collaboration databases, manual searches of the references of identified articles, and review articles on collagenous or microscopic colitis, as well as searches of abstracts from major gastroenterological meetings.. Five randomized trials assessing treatments for collagenous colitis were identified. One trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 wk) included 9 patients. Patients who received the bismuth preparation were more likely to have clinical (p= 0.003) and histological (p= 0.003) improvement than those who received placebo. In a trial comparing prednisolone (50 mg daily for 2 wk) to a placebo in 11 patients, a trend toward clinical response in patients on prednisone was reported (p= 0.064). The effect of prednisolone on histological improvement was not studied. A total of 94 patients were enrolled in three trials studying budesonide (9 mg daily or in a tapering schedule for 6-8 wk). The pooled odds ratio for clinical response to treatment with budesonide was 12.32 (95% CI: 5.53-27.46). The NNT (number of patients needed to treat with budesonide to achieve 1 improved patient) was 2 patients. This therapy was well tolerated. There was significant histological improvement with treatment in all three trials studying budesonide therapy.. There is strong evidence that budesonide is effective and well tolerated for the treatment of collagenous colitis. The evidence for benefit with bismuth subsalicylate or prednisolone is weaker. It is not clear that any of these agents produce actual remission, as opposed to clinical and histological improvement of the disease.

Topics: Anti-Inflammatory Agents; Bismuth; Budesonide; Chi-Square Distribution; Colitis, Collagenous; Double-Blind Method; Humans; Organometallic Compounds; Prednisolone; Randomized Controlled Trials as Topic; Salicylates

Collagenous colitis is a disorder that is recognized as a cause of chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This review was performed to identify therapies for collagenous colitis that have been proven in randomized trials.. To determine effective treatments for patients with clinically active collagenous colitis.. Relevant papers published between 1970 and October 2002 were identified via the MEDLINE, PUBMED, and EMBASE databases. Manual searches from the references of identified papers, as well as review papers on collagenous or microscopic colitis were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Finally, the Cochrane Controlled Trials Register and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were searched for other studies.. Four randomized trials were identified. One trial studied bismuth subsalicylate (published in abstract form only), and 3 trials (1 published in abstract form only) studied budesonide in the therapy of collagenous colitis.. Data were extracted independently by each author onto 2x2 tables (treatment versus placebo and response versus no response). For therapies assessed in one trial only, p-values were derived using the chi-square test. For therapies assessed in more than one trial, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals. Data were combined for analysis only if the outcomes were sufficiently similar in definition.. There were 9 patients with collagenous colitis in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks). Those randomized to active drug were more likely to have clinical (p=0.003) and histological (p=0.003) improvement than those assigned to placebo. A total of 94 patients were enrolled in 3 trials studying budesonide (9 mg daily for 6 to 8 weeks). The pooled odds ratio for clinical response to treatment with budesonide was 12.32 (95% CI 5.53-27.46), with a number needed to treat of 2 patients. There was significant histological improvement with treatment in all 3 trials studying budesonide therapy.. Budesonide is effective in the treatment of collagenous colitis. The evidence for bismuth subsalicylate is weaker, but still important. The roles of these and other therapies in inducing or maintaining remission (as opposed to clinical or histological improvement) of collagenous colitis are unknown.

Topics: Anti-Inflammatory Agents; Bismuth; Budesonide; Chronic Disease; Colitis; Diarrhea; Humans; Organometallic Compounds; Salicylates

Microscopic colitis (MC) encompasses the two morphologically distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). MC was first described less than 30 years ago but is presently recognized as a relatively common cause of chronic diarrhea in the adult population. Remarkably, up to 10% of adults who have a colonoscopy for the investigation of chronic diarrhea, and have endoscopically normal appearing mucosa, may have MC. Patients with MC generally present with chronic diarrhea, which can be associated with cramping and bloating. Endoscopic and radiological examinations are usually normal. Histological assessment reveals inflammation consisting predominantly of lymphocytic infiltration, and a thickened subepithelial collagen band is diagnostic of CC. Both LC and CC can be associated with autoimmune diseases such as celiac disease, diabetes, arthritis and thyroiditis, yet the mechanisms involved in the pathogenesis remain unclear. Emerging studies suggest that a stepwise approach be taken in the medical management of MC. This approach includes antidiarrheal agents and stopping of any offending agents; budesonide or bismuth subsalicylate; and cholestyramine or 5-acetylsalicylic acid agents. In resistant cases, oral corticosteroids and other immune modulatory therapy have been used.

Topics: Algorithms; Antidiarrheals; Bismuth; Budesonide; Colitis; Humans; Organometallic Compounds; Salicylates; T-Lymphocytes

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Proton Pump Inhibitors; Ranitidine; Salicylates; Virulence

Collagenous colitis is a disorder that is recognized as a cause of chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This review was performed to identify therapies for collagenous colitis that have been proven in randomized trials.. To determine effective treatments for patients with clinically active collagenous colitis.. Relevant papers published between 1970 and January 2002 were identified via the MEDLINE, PUBMED, and EMBASE databases. Manual searches from the references of identified papers, as well as review papers on collagenous or microscopic colitis were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Finally, the Cochrane Controlled Trials Register and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were searched for other studies.. Four randomized trials were identified. One trial studied bismuth subsalicylate (published in abstract form only), and 3 trials (2 published in abstract form only) studied budesonide in the therapy of collagenous colitis.. Data were extracted independently by each author onto 2x2 tables (treatment versus placebo and response versus no response). For therapies assessed in one trial only, p-values were derived using the chi-square test. For therapies assessed in more than one trial, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals. Data were combined for analysis only if the outcomes were sufficiently similar in definition.. There were 9 patients with collagenous colitis in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks). Those randomized to active drug were more likely to have clinical (p=0.003) and histological (p=0.003) improvement than those assigned to placebo. A total of 86 patients were enrolled in 3 trials studying budesonide (9 mg daily for 6 to 8 weeks). The pooled odds ratio for clinical response to treatment with budesonide was 16.79 (95% CI 7.28-38.74), with a number needed to treat of 2 patients. There was significant histological improvement with treatment in all 3 trials studying budesonide therapy.. Budesonide is effective in the treatment of collagenous colitis. The evidence for bismuth subsalicylate is weaker, but still important. The roles of these and other therapies in inducing or maintaining remission (as opposed to clinical or histological improvement) of collagenous colitis are unknown.

Topics: Anti-Inflammatory Agents; Bismuth; Budesonide; Colitis; Collagen; Humans; Organometallic Compounds; Randomized Controlled Trials as Topic; Salicylates

Topics: Amoxicillin; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Salicylates; Tetracycline

Helicobacter pylori eradication decreases ulcer recurrence and should prevent recurrent ulcer haemorrhage.. By meta-analysis, to compare treatment of H. pylori infection with other approaches to prevent recurrent ulcer haemorrhage and, by cost minimization analysis, to determine the least costly strategy.. We searched for randomized, controlled trials comparing treatment of H. pylori infection with ulcer healing alone or with maintenance therapy in preventing recurrent ulcer haemorrhage. We calculated the relative and absolute risk reductions and numbers needed to treat.. Treatment of H. pylori infection decreased recurrent bleeding by 17% (numbers needed to treat=6) compared with ulcer healing treatment alone. Compared with ulcer healing treatment followed by maintenance therapy, recurrent bleeding was decreased by 4% (numbers needed to treat=25). Decision model-based cost minimization analysis demonstrated that treatment of H. pylori infection was the least costly strategy unless the incidence of complicated recurrences after treatment was over 6%, or the cost of confirming eradication was over $741.. Treatment of H. pylori infection is superior to ulcer healing treatment with or without maintenance therapy in preventing recurrent ulcer haemorrhage. All patients with ulcer bleeding should be tested for H. pylori infection and appropriately treated if positive.

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; MEDLINE; Metronidazole; Omeprazole; Organometallic Compounds; Peptic Ulcer Hemorrhage; Randomized Controlled Trials as Topic; Ranitidine; Recurrence; Risk Factors; Salicylates; Sensitivity and Specificity

Complaints of "excessive gas" from patients are very common but are difficult, if not impossible, for the physician to document. This review addresses the pathophysiology and management of such complaints, looking at the sources and routes of elimination, excessive eructation, bloating, and distention. In addition, common flatulence problems are summarized, including excessive flatus volume and noxious flatus.

Topics: Bismuth; Charcoal; Diagnosis, Differential; Eructation; Flatulence; Humans; Organometallic Compounds; Salicylates

The pharmacist is an important specialist in the selection of the drug when the patient comes for pharmacist's advice of how to alleviate common gastrointestinal symptoms. Of all drugs which can be effective in these situations, only three drugs (bismuth subsalicylate, psyllium, and docusate sodium) proved to be advantageous for self-medication. Bismuth subsalicylate (BSS) is much appreciated in the treatment of peptic ulcers where it not only covers the base of the ulcer but also eradicates Helicobacter pylori. Therefore this drug does not treat only the symptoms but the cause of the disease as well. Dyspepsia may also be effectively treated with BSS because of its strong and rapid protective effect on the gastric mucosa. Last but not least, the salicylate component of this substance and not bismuth alone is responsible for the elimination of diarrhoea in the so-called traveller's diarrhoea, as the salicylate decreases enhanced secretion of fluid in the colon. On the other hand, the natural fibre psyllium may effectively alleviate constipation, because it increases the volume and weight of stools as well as the transit time in the colon and facilitates defecation. Similarly, docusate sodium is a detergent agent which facilitates the entrance of water into the stool, which is then better and more easily pushed out from the large intestine.

Topics: Bismuth; Cathartics; Dioctyl Sulfosuccinic Acid; Gastrointestinal Diseases; Humans; Organometallic Compounds; Psyllium; Salicylates

Topics: Antibiotic Prophylaxis; Behavior Therapy; Bismuth; Diagnosis, Differential; Diarrhea; Humans; Organometallic Compounds; Salicylates; Travel; Vaccines

Patients with Helicobacter pylori-induced duodenal ulcer should have their infection eradicated. The optimal choice of antibiotic therapy, however, is less clear.. To evaluate costs and outcomes of treatment with 8 antibiotic regimens with documented activity against H pylori vs maintenance therapy with histamine2-receptor antagonists (H2RA).. A meta-analysis for 119 studies enrolling 6416 patients to determine aggregate eradication rates. The complexity of each regimen was used to determine the anticipated compliance rate and actual effectiveness. A decision analytic model with Monte Carlo simulation determined annual costs and health outcomes.. Average annual total costs of testing for H pylori infection and antibiotic treatment ranged from $223 to $410 and prevented ulcer recurrence in 70% to 86% of patients. The H2RA maintenance therapy cost $425 and prevented recurrence in 72% of patients. The lowest costs and recurrence rates were achieved by 3 regimens: standard triple therapy (a combination of bismuth subsalicylate, metronidazole, and tetracycline hydrochloride) for 14 days ($223, with 18% recurrence); a combination of clarithromycin, metronidazole, and a proton pump inhibitor for 7 days ($235, with 15% recurrence); and standard triple therapy with a proton pump inhibitor for 7 days ($236, with 14% recurrence).. Treatment with any regimen resulted in lower costs compared with H2RA maintenance therapy. Three antibiotic regimens had consistently lower costs and better outcomes: standard triple therapy for 14 days, metronidazole, clarithromycin, and a proton pump inhibitor for 7 days, and standard triple therapy plus a proton pump inhibitor for 7 days.

Topics: Anti-Bacterial Agents; Bismuth; Clarithromycin; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Monte Carlo Method; Organometallic Compounds; Patient Compliance; Proton Pump Inhibitors; Recurrence; Salicylates; Tetracycline; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Salicylates; Tetracycline

Bismuth salts have been used in medicine for over three centuries, particularly in the treatment of dyspepsia. Commonly used agents include colloidal bismuth subcitrate (CBS), bismuth subsalicylate (BSS) and the newer ranitidine bismuth citrate (RBC). These are safe drugs which exert local effects on the gastroduodenal mucosa. Gastric mucosal levels of bismuth exceed the concentrations required to kill Helicobacter pylori in vitro. The mechanisms of actions of bismuth on gastrointestinal pathogens including H. pylori are complex and include inhibition of protein and cell wall synthesis, membrane function and ATP synthesis. Adherence of H. pylori to surface epithelial cells is also impaired. Bismuth monotherapy is effective in vivo to suppress H. pylori but cure rates are low. CBS, BSS and RBC have synergistic activity with one or two antibiotics and are effective in eradicating H. pylori. CBS and RBC also exert other effects on the mucosa including cytoprotective and ulcer healing properties. In addition, RBC is effective in inhibiting gastric acid secretion.

Topics: Anti-Bacterial Agents; Bismuth; Drug Synergism; Duodenum; Gastric Acid; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Organometallic Compounds; Ranitidine; Salicylates; Treatment Outcome

Peptic ulcer disease is strongly associated with infection by Helicobacter pylori, a spiral-shaped, flagellated organism found predominantly in the gastric antrum. More than 90 percent of duodenal ulcers and adenocarcinomas of the distal stomach are associated with H. pylori infection. Eradication of the organism effectively prevents relapses of gastroduodenal ulcers associated with H. pylori. In patients undergoing endoscopy, the rapid urease test is highly sensitive and specific in diagnosing H. pylori infection. Noninvasive diagnostic methods include serologic antibody measurements and urea breath testing. Empiric therapy may be tried if the diagnosis is suspected on a clinical basis. Traditional 14-day "triple therapy" with bismuth, metronidazole and either amoxicillin or tetracycline has consistently produced eradication rates of approximately 90 percent. Newer combination regimens have shown promise in a smaller number of studies. No single agent given as monotherapy has proved to be acceptably effective in clinical studies.

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Organometallic Compounds; Penicillins; Peptic Ulcer; Protein Synthesis Inhibitors; Salicylates; Tetracycline

Diarrhea represents a major health problem for travelers to developing countries. Although the syndrome is usually self-limited and recovery occurs in the majority of cases without any specific form of therapy, there is a need for safe and effective ways of preventing and treating it. Since the syndrome is most often caused by an infection acquired by ingesting fecally contaminated food or beverages, precautions regarding dietary habits remain the cornerstone of prophylaxis, but dietary self-restrictions do not always translate to reduced rates of diarrheal illness. Administration of probiotics (e.g. lactobacilli or Saccharomyces boulardii) and immunoprophylaxis with the newer oral cholera vaccines have been tried with promising results. Antimicrobials remain, however, the most successful form of prophylaxis, being effective in up to 90% of travelers. For those with impaired health who will take prophylaxis, systemic agents with proved efficacy should be recommended. For other otherwise healthy persons, poorly absorbed agents are preferable in order to avoid the serious, albeit rare, toxicity of systemic drugs. The key factor in the management of acute watery traveler's diarrhea, particularly in infants and young children, is the restoration of water and electrolyte balance. This does not reduce the duration of the illness but will limit dehydration and prevent acidosis. Many patients will require no additional therapy, whereas some will need pharmacologic treatment to shorten the duration of diarrhea or to relieve the accompanying symptoms, like abdominal discomfort, nausea and vomiting. A typical 3- to 5-day illness can be reduced to approximately 1 day by trimethoprim-sulfamethoxazole (TMP-SMX) combination. Some other systemic antimicrobials have been successfully used but, during the last few years, the 4-fluoroquinolone drugs have received considerable attention and have been shown to be highly effective in reducing the duration of traveler's diarrhea. These antimicrobials may become the best option for adults. The safest choice remains the use of poorly absorbed antimicrobials. Unfortunately, however, only a few compounds (i.e. bicozamycin and furazolidone) have been specifically tested in the therapy of traveler's diarrhea. Others (e.g. nifuroxazide or rifaximin), which have been found effective in various homeland forms of infective diarrhea deserve to be evaluated in specifically designed clinical trials. Persons visiting developing countries whe

Topics: Anti-Bacterial Agents; Antibiosis; Antidiarrheals; Bismuth; Clinical Trials as Topic; Diarrhea; Feeding Behavior; Fluid Therapy; Food Microbiology; Humans; Lactobacillus; Organometallic Compounds; Salicylates; Travel; Water Microbiology; Water Supply

Topics: Antacids; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Gastric Acid; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metronidazole; Organometallic Compounds; Peptic Ulcer; Salicylates; Tetracycline

Gastric pseudolymphoma is a rare disorder of unknown etiology that can undergo transformation into malignant lymphoma. This report describes the first case of a gastric pseudolymphoma associated with Helicobacter pylori infection that underwent complete clinical, endoscopic, and histologic resolution following treatment with bismuth subsalicylate, amoxicillin, and metronidazole. The eradication of Helicobacter pylori may have eliminated ongoing antigenic stimulation that has previously been postulated to be responsible for the development and subsequent progression of gastric pseudolymphoma.

Topics: Aged; Amoxicillin; Biopsy; Bismuth; Drug Therapy, Combination; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytes; Male; Metronidazole; Organometallic Compounds; Ranitidine; Salicylates; Stomach; Stomach Neoplasms

Topics: Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Peptic Ulcer; Salicylates; Tetracycline; United States

Now that Helicobacter pylori has been strongly implicated as a causative factor in peptic ulcer disease, the dictum "no acid--no ulcer" may no longer be valid. However, H pylori has proved difficult to eradicate, and the approach to treatment of peptic ulcer is undergoing changes. At present, a triple-drug combination of bismuth and antibiotics is advised, and cultures should be obtained before and after treatment to monitor its efficacy. Side effects include pseudomembranous colitis and drug resistance.

Topics: Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Peptic Ulcer; Salicylates

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Peptic Ulcer; Recurrence; Salicylates

Topics: Bismuth; Body Water; Breath Tests; Child, Preschool; Chronic Disease; Diagnosis, Differential; Diarrhea, Infantile; Dicyclomine; Dietary Carbohydrates; Fruit; Gastrointestinal Motility; Humans; Infant; Infant, Newborn; Intestinal Diseases, Parasitic; Lactose Intolerance; Loperamide; Malabsorption Syndromes; Myoelectric Complex, Migrating; Organometallic Compounds; Salicylates

Preventing traveler's diarrhea is usually a matter of common sense, good luck, and the host's ability to defend against enteric pathogens, particularly enterotoxigenic Escherichia coli. Untreated tap water, ice cubes, unpasteurized milk products, salads, food from street vendors, and dining in unhygienic-appearing restaurants should be avoided. Well-cooked food that is served hot and carbonated, commercially bottled beverages are usually safe. Food and water precautions, however, are no guarantee of success in preventing traveler's diarrhea. Bismuth subsalicylate used prophylactically is somewhat inconvenient and is only moderately effective. Although antibiotic prophylaxis is very effective for traveler's diarrhea, particularly the quinolones, it should be reserved for high-risk travelers.

Topics: Anti-Bacterial Agents; Bismuth; Diarrhea; Food Microbiology; Humans; Organometallic Compounds; Risk Factors; Salicylates; Travel; Water Microbiology; Water Supply

Topics: Anti-Bacterial Agents; Biopsy; Bismuth; Child; Clinical Trials as Topic; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Evaluation Studies as Topic; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Prevalence; Salicylates

Helicobacter pylori is a recently identified microorganisms which is thought to be the causing agent of the peptic acid disease in children as well as in adults. It is currently accepted that frequent relapses of this illness in spite of an adequate treatment can be associated to the faulty eradication of this bacteria. This article outlines the characteristics of H. pylori, its incidence, pathogenesis, as well as the current diagnostic methods used and the treatment applied.

Topics: Anti-Bacterial Agents; Bismuth; Child; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Peptic Ulcer; Salicylates

Travellers' diarrhoea is a common problem worldwide and is likely to continue to increase with the expansion of foreign travel. ETEC is the most frequently isolated enteropathogen although other bacteria, parasites and viruses may be important, depending on the geographic location. New pathogens may well emerge in the future. Prevention must be the ultimate goal but while awaiting effective vaccines we must be content with the traditional dietary advice and its often unpalatable and unacceptable restrictions. Antibiotic prophylaxis is clearly effective but for the present should be restricted to high risk individuals and in those in whom any disruption of a short stay would be critical. For those taking antibiotic prophylaxis advice, as always, should be given regarding the possible adverse effects. Concern about the emergence of resistant strains may be less with the new 4-fluoroquinolone antibiotics. Alternatives for prophylaxis include bismuth subsalicylate which is safe and not an environmental hazard. We must await developments in the Lactobacillus sp. story to see whether the use of probiotics have any role in the prevention of travellers' diarrhoea. Antimotility agents have no place in prophylaxis. The cornerstone of treatment of travellers' diarrhoea is the maintenance of fluid and electrolyte balance. It is particularly important in infants and young children and should be given in the form of oral glucose-electrolyte solutions of which there are many effective preparations. A variety of antibiotics are now known to reduce the duration of travellers' diarrhoea but there is still concern about the risk of therapy for what is usually a minor illness of inconvenience. However, when the loss of 1 or 2 days during a short visit is critical, one could opt for a short course of antibiotics (trimethoprim-sulphamethoxazole, or a 4-fluoroquinolone for 3 days or less) in combination with an antidiarrhoeal trimethoprim alone agent such as loperamide.

Topics: Anti-Bacterial Agents; Bismuth; Diarrhea; Diet; Fluid Therapy; Humans; Organometallic Compounds; Risk Factors; Salicylates; Travel

Bismuth subsalicylate (BSS) has been used for more than 80 years to treat gastrointestinal symptoms although little clinical evidence was available until recently to substantiate its value and possible mechanisms of action. BSS 4.2 g given over 3 1/2 hours was shown to reduce the number of stools passed and favorably alter subjective symptoms in patients with traveler's diarrhea. BSS has also been shown to have beneficial effects on chronic infantile diarrhea. A small but discernible effect has been shown on selected symptoms associated with Norwalk virus-induced gastroenteritis. A liquid preparation, in a dose of 60 ml qid (4.2 g/d), was 62 percent effective in preventing traveler's diarrhea during a three-week period of risk and a tablet formulation (BSS 600 mg qid) was 76 percent effective in preventing experimentally induced enterotoxigenic Escherichia coli diarrhea in volunteers. A tablet formulation (2.1 g/d) was recently shown to be 65 percent effective in preventing traveler's diarrhea during a three-week clinical trial in Mexico. Preliminary evidence suggests that the salicylate moiety exerts antisecretory effects in patients with diarrhea and the bismuth and intestinal hydrolysis products of BSS have direct antimicrobial effects.

Topics: Adolescent; Adult; Bismuth; Child; Child, Preschool; Clinical Trials as Topic; Diarrhea; Humans; Middle Aged; Organometallic Compounds; Salicylates

Topics: Bismuth; Campylobacter Infections; Chronic Disease; Dose-Response Relationship, Drug; Gastritis; Humans; Organometallic Compounds; Salicylates

Various available forms of therapy can decrease morbidity and mortality associated with acute diarrhea. Oral fluids represent the cornerstone of therapy of all cases. A variety of agents acting nonspecifically can decrease diarrhea and improve other worrisome symptoms associated with enteric infection. Kaopectate makes the stool more formed but has little additional effects. Bismuth subsalicylate, an antisecretory agent, reduces the number of stools passed by about 50 percent and improves other associated symptomatology. The drugs that affect motility such as loperamide and diphenoxylate are the most active of the nonspecifically acting drugs. They must be avoided in patients with significant fever and dysentery. Trimethoprim/sulfamethoxazole is now considered the drug of choice for shigellosis due to the presence of ampicillin-resistant Shigella strains in most regions of the world. Trimethoprim/sulfamethoxazole is also an effective form of therapy for enterotoxigenic Escherichia coli infection and for traveler's diarrhea without definable cause. Erythromycin, although not proved to be effective against Campylobacter, probably shortens the disease. Furazolidone, although not dramatically effective, has a spectrum of activity that includes Shigella, enterotoxigenic E. coli, Campylobacter, and Giardia lamblia. It may not be effective in severely ill (hospitalized) patients with diarrhea. The various forms of available therapy can be administered empirically, depending on symptomatology. Mildly ill patients (one to three unformed stools in 24 hours with minimal additional symptoms) probably are best treated with fluids only. Mild to moderately ill persons (three to six unformed stools in 24 hours) can be treated with a drug that acts nonspecifically, such as bismuth subsalicylate or loperamide. Those with severe diseases (six or more unformed stools with moderate to severe associated symptoms), particularly when associated with fever and the passage of bloody mucoid stools, may be given an antimicrobial agent. The antimicrobial drug given will be determined by ancillary laboratory tests (dark-field examination or examination of a wet-mount preparation for motile Campylobacter or stool culture for Shigella, Campylobacter, or Salmonella) or may be administered on an empiric basis. Traveler's diarrhea can be eliminated in selected persons by the administration of a pharmacologic agent. Liquid bismuth subsalicylate is effective in large doses, which may be impr

Topics: Acute Disease; Adult; Anti-Infective Agents; Bismuth; Campylobacter Infections; Child; Child, Preschool; Clinical Trials as Topic; Diarrhea; Diarrhea, Infantile; Drug Combinations; Dysentery, Amebic; Dysentery, Bacillary; Escherichia coli Infections; Giardiasis; Humans; Infant; Kaolin; Loperamide; Narcotics; Organometallic Compounds; Parasympatholytics; Pectins; Salicylates; Salmonella Infections; Travel

Three hundred million people, mostly tourists, participate in international travel each year. Development of an acute diarrheal syndrome abroad, while returning home, or shortly after arriving home is referred to as traveler's diarrhea (TD). TD is not a specific diagnosis but, rather, a clinical syndrome with multiple etiologies. In this article, clinical and epidemiological features of TD, specific etiologies and their pathogenesis, as well as current means of diagnosis, treatment, and prevention will be reviewed.

Topics: Anti-Bacterial Agents; Antidiarrheals; Bismuth; Campylobacter Infections; Diarrhea; Diet; Dysentery, Bacillary; Escherichia coli Infections; Fluid Therapy; Giardiasis; Humans; Intestines; Organometallic Compounds; Risk; Salicylates; Salmonella Infections; Time Factors; Travel; Vaccination; Vibrio Infections; Vibrio parahaemolyticus

Two experiments were performed to evaluate the effects of bismuth subsalicylate (BSS) and calcium-ammonium nitrate (CAN) on in vitro ruminal fermentation, growth, apparent total tract digestibility of nutrients, liver mineral concentration, and carcass quality of beef cattle. In Exp. 1, four ruminally cannulated steers (520 ± 30 kg body weight [BW]) were used as donors to perform a batch culture and an in vitro organic matter digestibility (IVOMD) procedure. Treatments were arranged in a 2 × 2 factorial with factors being BSS (0 or 0.33% of substrate dry matter [DM]) and CAN (0 or 2.22% of substrate DM). In Exp. 2, 200 Angus-crossbred steers (385 ± 27 kg BW) were blocked by BW and allocated to 50 pens (4 steers/pen) in a randomized complete block design with a 2 × 2 + 1 factorial arrangement of treatments. Factors included BSS (0 or 0.33% of the diet DM) and nonprotein nitrogen (NPN) source (urea or encapsulated CAN [eCAN] included at 0.68% or 2.0% of the diet, respectively) with 0.28% ruminally available S (RAS). A low S diet was included as a positive control containing urea (0.68% of DM) and 0.14% RAS. For Exp. 1, data were analyzed using the MIXED procedure of SAS with the fixed effects of BSS, CAN, BSS × CAN, and the random effect of donor. For Exp. 2, the MIXED procedure of SAS was used for continuous variables and the GLIMMIX procedure for categorical data. For Exp. 1, no differences (P > 0.230) were observed for IVOMD. There was a tendency (P = 0.055) for an interaction regarding H2S production. Acetate:propionate increased (P = 0.003) with the addition of CAN. In Exp. 2, there was a NPN source effect (P = 0.032) where steers consuming urea had greater carcass-adjusted final shrunk BW than those consuming eCAN. Intake of DM (P < 0.001) and carcass-adjusted average daily gain (P = 0.024) were reduced by eCAN; however, it did not affect (P = 0.650) carcass-adjusted feed efficiency. Steers consuming urea had greater (P = 0.032) hot carcass weight, and a BSS × NPN interaction (P = 0.019) was observed on calculated yield grade. Apparent absorption of S decreased (P < 0.001) with the addition of BSS. Final liver Cu concentration was reduced (P = 0.042) by 58% in cattle fed BSS, indicating that BSS may decrease Cu absorption and storage in the liver. The results observed in this experiment indicate that BSS does not have negative effects on feedlot steer performance, whereas CAN may hinder performance of steers fed finishing diets.

Topics: Animal Feed; Animals; Bismuth; Calcium; Cattle; Diet; Digestion; Nitrates; Organometallic Compounds; Rumen; Salicylates

Antibiotic-resistance reduces the efficacy of conventional triple therapy for Helicobacter Pylori infections worldwide, which necessitates using various treatment protocols. We used two protocols, doxycycline-based quadruple regimen and concomitant levofloxacin regimen. The aim was to assess the effectiveness of doxycycline-based quadruple regimen for treating Helicobacter Pylori infections compared with levofloxacin concomitant regimen as empirical first-line therapy based on intention-to-treat (ITT) and per-protocol analyses (PPA) in Syrian population.. An open-label, randomised, parallel, superiority clinical trial.. We randomly assigned 78 naïve patients who tested positive for Helicobacter Pylori gastric infection, with a 1:1 ratio to (D-group) which received (bismuth subsalicylate 524 mg four times daily, doxycycline 100 mg, tinidazole 500 mg, and esomeprazole 20 mg, each twice per day for 2 weeks), or (L-group) which received (levofloxacin 500 mg daily, tinidazole 500 mg, amoxicillin 1000 mg, and esomeprazole 20 mg each twice per day for two weeks). We confirmed Helicobacter Pylori eradication by stool antigen test 8 weeks after completing the treatment.. Thirty-nine patients were allocated in each group. In the D-group, 38 patients completed the follow-up, 30 patients were cured. While in the L-group, 39 completed the follow-up, 32patients were cured. According to ITT, the eradication rates were 76.92%, and 82.05%, for the D-group and L-group respectively. Odds ratio with 95% confidence interval was 1.371 [0.454-4.146]. According to PPA, the eradication rates were 78.9%, and 82.05% for the D-group and L-group respectively. The odds ratio with 95% confidence interval was 1.219 [0.394-3.774]. We didn't report serious adverse effects.. Levofloxacin concomitant therapy wasn't superior to doxycycline based quadruple therapy. Further researches are required to identify the optimal first-line treatment for Helicobacter-Pylori Infection in the Syrian population.. We registered this study as a standard randomized clinical trial ( Clinicaltrial.gov , identifier- NCT04348786 , date:29-January-2020).

Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Bismuth; Doxycycline; Drug Therapy, Combination; Esomeprazole; Feces; Female; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Male; Middle Aged; Organometallic Compounds; Prospective Studies; Salicylates; Syria; Tinidazole; Treatment Outcome; Young Adult

Many of the 4.5 billion annual episodes of diarrhea are treated unnecessarily with antibiotics; prevalence of antibiotic resistance among diarrheal pathogens is increasing. Knowledge-based antibiotic stewardship interventions typically yield little change in antibiotic use.. To compare antibiotic use among adult outpatients with diarrhea given bismuth subsalicylate (BSS) or placebo.. This randomized clinical trial took place from April to October 2014. Participants were patients aged 15 to 65 years with acute, nonbloody diarrhea from 22 outpatient clinics in Karachi, Pakistan. Participants were interviewed about symptoms and health care utilization during the 5 days after enrollment. Group assignment was concealed from participants, field staff, and the statistician. Primary analysis occurred from August to September 2015.. Participants were randomly assigned (1:1) to receive BSS or placebo for 48 hours or less.. Use of systemic antibiotics within 5 days of enrollment. Secondary outcomes included measures of duration and severity of illness.. Among eligible patients, 39 declined to participate, 440 enrolled, and 1 enrolled participant was lost to follow-up, for a total of 439 patients included in the analysis. Median (interquartile range) participant age was 32 (23-45) years and 187 (43%) were male. Two hundred twenty patients were randomized to BSS and 220 were randomized to placebo. Overall, 54 participants (12%) used systemic antibiotics (16% in the placebo group and 9% in the BSS group); all antibiotic use followed consultation with a physician. Use of any antibiotic was significantly lower in the BSS group (20 of 220 vs 34 of 219 patients; odds ratio [OR], 0.54; 95% CI, 0.30-0.98), as was use of fluoroquinolones (8 of 220 vs 20 of 219 patients; OR, 0.38; 95% CI, 0.16-0.88). Rates of care seeking and hospitalization were similar between groups and no difference was detected in timing of diarrhea resolution. However, those in the BSS group less commonly received intravenous rehydration (14 of 220 vs 27 of 219 patients; OR, 0.48; 95% CI, 0.25-0.95) and missed less work (median [interquartile range], 0 [0-1] vs 1 [0-1] day; P = .04) during follow-up.. This study found less antibiotic use among participants given BSS for acute diarrhea in a setting where antibiotics are commonly used to treat diarrhea. Encouraging health care professionals in such settings to recommend BSS as frontline treatment for adults with diarrhea, and promoting BSS for diarrhea self-management, may reduce antibiotic use and rates of antibiotic resistance globally.. ClinicalTrials.gov identifier: NCT02047162.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antidiarrheals; Antimicrobial Stewardship; Bismuth; Diarrhea; Drug Utilization; Female; Follow-Up Studies; Humans; Inappropriate Prescribing; Logistic Models; Male; Middle Aged; Organometallic Compounds; Pakistan; Practice Patterns, Physicians'; Salicylates; Young Adult

Standard triple therapy for Helicobacter pylori has a low eradication rate in Turkey. The aim of this study was to evaluate and compare the effectiveness of 7-day and 14-day lansoprazole, amoxicillin, clarithromycin, and bismuth subsalicylate (LACB) treatment regimens as first-line H. pylori eradication therapies.. This study included 70 patients with symptoms of dyspepsia and a positive H. pylori stool antigen test (SAT). Thirty-five patients received the modified quadruple therapy regimen for 7 days (LACB-7) whereas the remaining 35 patients received the treatment for 14 days (LACB-14). Eradication was assessed by SAT 1 month after the end of therapy.. A total of 64 patients completed the therapy. The cumulative per-protocol (PP) and intention-to-treat (ITT) eradication rates were 89% (n = 57/64) and 81.4% (n = 57/70), respectively. Both the PP and ITT eradication rates were superior in the LACB-14 group, compared with the LACB-7 group (PP: 90.6% vs. 87.5%; ITT: 81.4% vs. 80%, respectively), but these differences were not statistically significant (P = 0.689).. Both the 7-day and 14-day first-line LACB therapies provided a high cure rate, were well tolerated, and were equally effective against H. pylori infection in Turkey.

Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Antidiarrheals; Bismuth; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Dyspepsia; Female; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Organometallic Compounds; Prospective Studies; Proton Pump Inhibitors; Salicylates

Flushing and gastrointestinal (GI) events are commonly associated with the use of delayed-release dimethyl fumarate (DMF) treatment for relapsing multiple sclerosis.. PREVENT (A Multicenter, Double-Blind, Placebo-Controlled Study of Pepto-Bismol [Bismuth Subsalicylate] on Gastrointestinal Tolerability in Healthy Volunteers Receiving Oral TECFIDERA [Dimethyl Fumarate] Delayed-Release Capsules Twice Daily) is a double-blind, placebo-controlled, 8-week study that evaluated the effect of bismuth subsalicylate on DMF-related GI events. Bismuth subsalicylate 524 mg or placebo were administered 30 min before DMF (weeks 1-4). DMF was dosed twice-daily (BID) at 120 mg (week 1) and 240 mg (weeks 2-8). Using an e-diary device, participants recorded GI and flushing events on the Modified Overall Gastrointestinal Symptom Scale once daily for the preceding 24 h. The primary end point was time to first GI-related event. Secondary end points included frequency and severity of GI-related events.. A total of 175 participants were enrolled (placebo, n = 87; bismuth subsalicylate, n = 88), and 17 discontinued treatment (placebo, n = 8; bismuth subsalicylate n = 9). A total of 146 participants reported ≥1 GI event: placebo, n = 72 (82.8%); and bismuth subsalicylate, n = 74 (84.1%). There was no statistical difference in risk of a GI event between the groups (P = 0.8292). Mean (SD) time from DMF initiation to first GI event was similar: placebo, 5.4 (8.73) days; and bismuth subsalicylate, 5.6 (10.87) days. Incidence of flatulence (38.6% vs 50.6%) and diarrhea (36.4% vs 48.2%) during weeks 1-4 was numerically lower in the bismuth subsalicylate group compared with the placebo group. Mean worst severity scores for flatulence (1.1 vs 1.8; P = 0.0219) and diarrhea (1.0 vs 1.6; P = 0.0500) were lower with bismuth subsalicylate than with placebo.. Although coadministration of bismuth subsalicylate did not affect the occurrence of DMF-related GI events overall, it reduced the severity and incidence of flatulence and diarrhea. ClinicalTrials.gov identifier: NCT01915901.

Topics: Adolescent; Adult; Antidiarrheals; Bismuth; Delayed-Action Preparations; Diarrhea; Dimethyl Fumarate; Double-Blind Method; Drug Therapy, Combination; Female; Flatulence; Healthy Volunteers; Humans; Immunosuppressive Agents; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Organometallic Compounds; Salicylates; Young Adult

The aim of this study was to compare the efficacy and safety of 2-week levofloxacin-containing triple therapy, levofloxacin-containing bismuth quadruple therapy, and standard bismuth-containing quadruple therapy as a first-line regimen for the eradication of Helicobacter pylori.. A total of 329 patients with H. pylori infection were randomly divided into 3 groups to receive one of the following regimens: (a) levofloxacin-containing bismuth quadruple therapy, RBAL (rabeprazole 20 mg, b.i.d., bismuth subsalicylate 562 mg, b.i.d., amoxicillin 1 g, b.i.d, levofloxacin 500 mg, once daily), (b) standard bismuth quadruple therapy, RBMT (rabeprazole 20 mg, b.i.d, subsalicylate 562 mg, b.i.d., metronidazole 500 mg, t.i.d, tetracycline 500 mg, q.i.d), or (c) levofloxacin-containing triple therapy, RAL (rabeprazole 20 mg, b.i.d., amoxicillin 1 g, b.i.d, levofloxacin 500 mg, once daily). The primary outcome was the eradication rate in the intention-to-treat (ITT) and per protocol (PP) analysis.. The eradication rates of the above 3 groups using ITT analysis were RBAL 83.8%, RBMT 88.3%, and RAL 74.8% compared with 91.2, 92.5, and 79.2%, respectively, using PP analysis. The eradication rate using RBMT was significantly higher than that of RAL (p = 0.029 in ITT analysis and p = 0.017 in PP analysis). Several side effects occurred in 156 patients (54.1%) in the RBAL group, 215 (52.3%) in the RBMT group, and 56 (26.2%) in the RAL group (p > 0.05, RBAL vs. RBMT; p < 0.001, RBMT vs. RAL; p < 0.001, RBAL vs. RAL).. All bismuth-containing quadruple therapies had acceptable eradication rates, but levofloxacin-containing triple therapy was not as good as quadruple therapies. Hence, quadruple therapies should be considered the preferred first-line therapy for H. pylori infections.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Female; Helicobacter Infections; Humans; Levofloxacin; Male; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Tetracycline; Young Adult

Levofloxacin is an effective medication for second line Helicobacter pylori (H. pylori) eradication. However, limited studies have approved its use as an effective antibiotic in first line therapy. Dexlansoprazole is a new PPI and lacks of evidence in support of a role in H. pylori eradication. This study was designed to evaluate efficacy of levofloxacin-dexlansoprazole-based quadruple therapy for H. pylori eradication in Thailand.. This prospective randomized control study was performed during June 2014 to December 2014. H. pylori infected gastritis patients were randomized to receive 7- or 14-day levofloxacin-dexlansoprazole based on quadruple therapy (levofloxacin 500 mg OD, dexlansoprazole 60 mg bid, clarithromycin MR 1000 mg OD, bismuth subsalicylate 1048 mg bid). CYP2C19 genotyping and antibiotic susceptibility tests were conducted for all patients. A 13C urea breath test was performed to confirm H. pylori eradication at least 4 weeks after treatment.. A total of 100 patients were enrolled, comprising 44 males and 56 females (mean age of 52.6 years). Eradication rate by PP analysis was 85.7% (42/49) with the 7-day regimen and 98% (48/49) with the 14-day regimen (85.7% vs 98%; p-value=0.059). ITT analysis was 84% and 96% with 7- and 14-day regimens, respectively (84% vs 96%; p-value=0.092). Antibiotic susceptibility testing demonstrated 35.1% resistance to metronidazole, 18.3% to clarithromycin, and 13.5% to levofloxacin. CYP2C19 genotyping revealed 54.1% RM, 34.7% IM and 11.2% PM. The 14-day regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and metronidazole H. pylori resistant strains. Moreover, the eradication rate was 96.6% in patients with CYP2C19 genotype RM.. The 14-day levofloxacin-dexlansoprazole based quadruple therapy provides high H. pylori eradication regardless of CYP2C19 genotype, clarithromycin or dual clarithromycin and metronidazole resistant strains. This regimen could be use as an alternative first line therapy for H. pylori eradication in Thailand.

Topics: Anti-Bacterial Agents; Antidiarrheals; Bismuth; Breath Tests; Clarithromycin; Cytochrome P-450 CYP2C19; Dexlansoprazole; Drug Therapy, Combination; Female; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Intention to Treat Analysis; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Organometallic Compounds; Prospective Studies; Proton Pump Inhibitors; Salicylates; Thailand

This study aimed at comparing the efficacy and tolerability of 5 different regimens for Helicobacter pylori eradication in recent years.. H. pylori-positive patients with dyspeptic symptoms were included and separated into 5 groups. The 'PAC group' was given pantoprazole, amoxicillin and clarithromycin for 14 days. The 'PAM group' was given pantoprazole, amoxicillin and metronidazole for 14 days. The 'bismuth-containing group' was given pantoprazole, bismuth subsalicylate, tetracycline and metronidazole for 14 days. The 'sequential group' was given pantoprazole and amoxicillin for 5 days, followed by pantoprazole, tetracycline, and metronidazole for the next 5 days. The 'concomitant group' was given pantoprazole, amoxicillin, tetracycline, and metronidazole for 10 days. Eradication was assessed through the urea breath test on 6 weeks after eradication therapy.. The eradication rate of intention-to-treat/per protocol were 42/48.3% in the PAC group, 52/54.2% in the PAM group, 62/77.5% in the bismuth group, 71/80.7% in the sequential group and 72/83.7% in concomitant group. The frequency of mild and moderate side effects was similar between groups.. The concomitant and sequential therapies are an effective treatment for H. pylori. Bismuth-containing therapy is superior to conventional triple therapies; however, the eradication rate is not satisfactory. In our country, conventional triple therapies are not effective for eradication.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Bacterial Agents; Bismuth; Breath Tests; Clinical Protocols; Disease Eradication; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Pantoprazole; Prospective Studies; Proton Pump Inhibitors; Salicylates; Turkey

We conducted a randomised single-blinded clinical trial of 100 cholera patients in Port-au-Prince, Haiti to determine if the probiotic Saccharomyces cerevisiae var. boulardii and the anti-diarrhoeal drug bismuth subsalicylate (BS) were able to reduce the duration and severity of cholera. Subjects received either: S. boulardii 250 mg, S. boulardii 250 mg capsule plus BS 524 mg tablet, BS 524 mg, or two placebo capsules every 6 hours alongside standard treatment for cholera. The length of hospitalisation plus the number and volume of emesis, stool and urine were recorded every 6 hours until the study subject was discharged (n = 83), left against medical advice (n = 11), or requested removal from the study (n = 6). There were no reported deaths or adverse study-related events. There were no statistically significant differences between the study arms and the outcomes of interest.

Topics: Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Bismuth; Cholera; Diarrhea; Disease Outbreaks; Emergency Medical Services; Feces; Female; Fluid Therapy; Haiti; Humans; Length of Stay; Male; Organometallic Compounds; Probiotics; Saccharomyces; Salicylates; Severity of Illness Index; Treatment Outcome; Vibrio cholerae

Helicobacter pylori (H. pylori) remains an important cause of gastric cancer and peptic ulcer disease worldwide. Treatment of H. pylori infection is one of the effective ways to prevent gastric cancer. However, standard triple therapy for H. pylori eradication is no longer effective in many countries, including Thailand. This study was designed to evaluate the efficacy of adding bismuth and probiotic to standard triple therapy for H. pylori eradication.. In this prospective single center study, H. pylori infected gastritis patients were randomized to receive 7- or 14-day standard triple therapy plus bismuth with probiotic or placebo. Treatment regimen consisted of 30 mg lansoprazole twice daily, 1 g amoxicillin twice daily, 1 g clarithromycin MR once daily and 1,048 mg bismuth subsalicylate twice daily. Probiotic bacteria composed of Bifidobacterium lactis, Lactobacillus acidophilus and Lactobacillus paracasei. Placebo was conventional drinking yogurt without probiotic. CYP2C19 genotyping and antibiotic susceptibility tests were also done. H pylori eradication was defined as a negative 13C-urea breath test at least 2 weeks after completion of treatment.. One hundred subjects were enrolled (25 each to 7- and 14-day regimens with probiotic or placebo). Antibiotic susceptibility tests showed 36.7% metronidazole and 1.1% clarithromycin resistance. CYP2C19 genotyping revealed 40.8%, 49% and 10.2% were rapid, intermediate and poor metabolizers, respectively. The eradication rates of 7- or 14 regimens with probiotics were 100%. Regarding adverse events, the incidence of bitter taste was significantly lower in the 7- day regimen with the probiotic group compared with 7- day regimen with placebo (40% vs. 64%; p=0.04).. The 7-day standard triple therapy plus bismuth and probiotic can provide an excellent cure rate of H. pylori (100%) in areas with low clarithromycin resistance such as Thailand, regardless of CYP2C19 genotype. Adding a probiotic also reduced treatment-related adverse events.

Topics: Amoxicillin; Anti-Bacterial Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Female; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Organometallic Compounds; Probiotics; Prognosis; Prospective Studies; Salicylates; Thailand

Pediatricians in Africa requested a tool to improve caregiver dosing of liquid antiretroviral medication. We developed, evaluated and disseminated a clip to control the amount of medication drawn into an oral syringe. In a laboratory, a user tested clips of different lengths, corresponding to different volumes, by drawing water into a syringe with a clip. In Texas and Malawi, 149 adults attempted to measure Pepto-Bismol™ using a syringe with a clip, a syringe without a clip, and a dosing cup, in a randomly assigned order. In the laboratory, the volume of liquid, ranging from 1 to 4.5 mL, drawn into the syringe was always within at least 5 μL of the intended dose. In Texas, 84% of doses were accurate within ±10%, vs. 63% using the syringe alone, and 21% with the dosing cup. In Malawi, 98% of doses were accurate to within ±10%, vs. 90% using the syringe alone, and 27% with the dosing cup. For target accuracy values within ±45% (±21%), a significantly higher fraction of Houston (Kamangira) participants delivered an accurate dose using the syringe with the clip than with the syringe alone (p < 0.05). The clip enables a greater proportion of users to accurately measure liquid medication.

Topics: Administration, Oral; Adult; Antidiarrheals; Bismuth; Equipment Design; Female; Humans; Male; Organometallic Compounds; Salicylates; Syringes

Helicobacter pylori eradication rates with standard triple regimens are worsening, and alternative treatments are urgently needed in some populations. The present study aimed to compare the efficacy of bismuth-based quadruple and concomitant regimens.. Consecutive Helicobacter pylori-positive patients with non-ulcer dyspepsia were randomized to receive one of two regimens: (i) bismuth subsalicylate 300 mg q.i.d., esomeprazole 40 mg b.i.d., tetracycline 500 mg q.i.d., and amoxicillin 1 g b.i.d. (bismuth group) or (ii) esomeprazole 40 mg b.i.d., tetracycline 500 mg q.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg t.i.d. (concomitant group) for 14 days. Gastroscopy and 14C-urea breath test were performed before enrollment, and urea breath test was repeated six weeks after the treatment.. A total of 200 patients were randomized, and 180 of them completed the protocols. The intention-to-treat and per-protocol eradication rates were 79% (95% confidence interval 71-87) and 89.7% (95% confidence interval 83-95) in the bismuth group and 74% (95% confidence interval 68-81) and 80.4% (95% confidence interval 72-87) in the concomitant group. The bismuth regimen achieved a slightly better eradication rate compared to the concomitant group in both per-protocol and intention-to-treat analysis, but results were not statistically significant (p>0.05). Ten patients (6 in bismuth, 4 in concomitant groups) dropped out of the study because of side effects.. The quadruple regimens with or without bismuth achieved moderate eradication rates as a first-line eradication option of Helicobacter pylori in our population, in which a bismuth-based regimen seems more appropriate. The compliance and side effects are important issues affecting the success of these regimens.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Ulcer Agents; Antidiarrheals; Bismuth; Drug Therapy, Combination; Esomeprazole; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Prospective Studies; Salicylates; Tetracycline; Young Adult

Confirmation of Helicobacter pylori eradication by urea breath test (UBT) is currently performed 4-6 weeks after completion of therapy because of unacceptable false-negative results in UBTs performed earlier. Use of a high-dose citric acid test meal appears to enable accurate detection of H. pylori even during short term therapy with proton pump inhibitors.. To evaluate if use of a high dose citric acid (4.0 g) test meal can decrease the interval required for confirmation of eradication after triple therapy.. 233 patients positive for H. pylori were randomized to undergo UBT at 7 days or 14 days after triple therapy, and again at 6 weeks. The latter test was considered the gold standard test.. The UBT performed 6 weeks after the end of treatment found that 79.9% were cured. The same test 7 days after therapy found false-negative detection of H. pylori in 7.3% patients compared to 3.2% patients examined after 14 days. The sensitivity, specificity, positive and negative predictive values and accuracy for evaluation on day 14 were 80, 100, 100, 96.3 and 96.7%, respectively.. High-dose citric acid-based UBT is a valid test for the assessment of H. pylori status 14 days after triple therapy. This may obviate the delay in instituting second-line eradication therapy, or further evaluation of the symptomatic patient unresponsive to therapy despite eradication.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bismuth; Breath Tests; Carbon Isotopes; Citric Acid; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Predictive Value of Tests; Salicylates; Sensitivity and Specificity; Treatment Outcome; Urea

Quadruple therapy provided inadequate eradication rate when given twice-a-day at breakfast and evening meals.. To test twice daily (mid-day and evening) quadruple therapy for Helicobacter pylori eradication.. This was a single-centre pilot study in which H. pylori-infected (positive histology and culture and RUT) patients were given 2 x 250 mg of metronidazole and 2 x 250 mg of tetracycline, two Pepto-Bismol tablets, plus one 20 mg rabeprazole tablet twice-a-day for 14 days. H. pylori status was confirmed 4 or more weeks after the end of therapy.. Thirty-seven patients including 3 with peptic ulcer disease, 19 asymptomatic infected, 4 GERD, and 11 with NUD. Mid-day quadruple therapy was successful in 92.3% (95% CI: 79-98%) including 96.2% of those with metronidazole-susceptible strains, and in 83.3% (10/12) of those with metronidazole-resistant H. pylori. Compliance was 100% by pill count except in one individual who stopped medication after 12 days because of side-effects and who failed therapy. Moderate or greater side-effects were experienced by five patients.. Twice-a-day, mid-day, quadruple therapy proved effective using the combination of bismuth subsalicylate and rabeprazole instead of bismuth subcitrate and omeprazole. Detailed studies of different formulations (e.g. 2 x 250 mg versus 1 x 500 mg of metronidazole or tetracycline) and timing of administration (breakfast and evening meal versus mid-day and evening meals) may result in significant improvements in H. pylori eradication regimens.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Antacids; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Ulcer Agents; Benzimidazoles; Bismuth; Drug Administration Schedule; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Patient Compliance; Pilot Projects; Prospective Studies; Proton-Translocating ATPases; Rabeprazole; Salicylates; Tetracycline; Treatment Outcome

We used data from a randomized placebo-controlled clinical trial to examine the relationship between Helicobacter pylori and reflux symptoms in nonulcer dyspepsia patients randomly assigned anti-Helicobacter pylori triple therapy alone, calcium carbonate alone, or in combination with triple therapy, tetracycline, or placebo. We compared risk differences for posttreatment Helicobacter pylori status and increased reflux symptoms from crude, multivariable and stratified multivariable analyses. In crude analyses, 54% of subjects without Helicobacter pylori after-treatment reported an increase in reflux compared to 41% of those with persistent infection (risk difference = 13%; P = 0.07). Only subjects with multifocal atrophic gastritis assigned to calcium carbonate reported an increase in reflux symptoms more frequently when Helicobacter pylori was absent versus when it persisted (risk difference = 52%; P = 0.0001). Therefore, the interaction of calcium carbonate use, chronic multifocal atrophic gastritis, and the absence of Helicobacter pylori may increase reflux symptoms.

Topics: Adult; Amoxicillin; Antacids; Bismuth; Calcium Carbonate; Drug Therapy, Combination; Dyspepsia; Female; Gastric Acidity Determination; Gastritis, Atrophic; Gastroesophageal Reflux; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Retrospective Studies; Risk Factors; Salicylates; Tetracycline

Eradication of Helicobacter pylori infection has had an impact on the treatment and recurrence rates of peptic ulcer disease and malignancies such as mucosa-associated lymphoid tissue lymphoma. Treatment options are cumbersome, expensive, and associated with side effects.. Randomized, prospective, open-labeled equivalence trial with a parallel-group design to compare eradication rates of H pylori with a 1-day, 4-drug regimen with a 7-day, 3-drug regimen. A total of 160 patients with dyspepsia and a Glasgow Dyspepsia Severity Score of at least 3 had a urea breath test labeled with carbon 14. Patients who tested positive were randomized to 1 of the 2 study groups. The study was designed to test the therapeutic equivalence of 1-day and 7-day regimens based on the percentage of H pylori eradication in each group at 5 weeks.. The 1-day treatment group (n = 80) had a slightly higher eradication percentage (95%) than the 7-day group (90%). The possible inferiority of the 1-day treatment relative to the 7-day treatment, a 15% difference in the number of patients whose infection was not eradicated at 5 weeks, was rejected (P<.001; 90% confidence interval, 2.7%-11%). Both groups demonstrated a mean decrease of 7.5 points in the Glasgow Dyspepsia Severity Score. The 2 groups showed no significant differences in side effects. Patients whose treatment failed (4 in the 1-day treatment group and 7 in the 7-day treatment group) were re-treated for 10 days. One patient from the 7-day treatment group still tested positive after the second treatment.. The 1-day treatment proved to be statistically similar to the 7-day treatment for the eradication of H pylori in patients with dyspepsia and a positive urea breath test. Further evaluation will be necessary to determine whether the 1-day regimen is adequate for patients with peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, or gastric adenocarcinoma.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Bismuth; Breath Tests; Drug Therapy, Combination; Dyspepsia; Female; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Prospective Studies; Proton Pump Inhibitors; Salicylates; Severity of Illness Index; Treatment Outcome

Antibiotic resistance has increasingly been recognized as the major cause of treatment failure for Helicobacter pylori infection. New therapies for patients with metronidazole- or clarithromycin-resistant H. pylori are needed.. To investigate the role of nitrofurantoin quadruple therapy for the treatment of H. pylori.. Patients with confirmed H. pylori infection received nitrofurantoin (100 mg t.d.s.), omeprazole (20 mg b.d.), Pepto-Bismol (two tablets t.d.s.), and tetracycline (500 mg t.d.s.) for 14 days. Four or more weeks after the end of therapy, outcome was assessed by repeat endoscopy with histology and culture or urea breath testing.. Thirty patients were entered, including 25 men and five women; the mean age was 54.9 years. The most common diagnoses were duodenal ulcer (23%) and GERD (18%). The intention-to-treat cure rate was 70% (95% CI: 50.6-85%). Nitrofurantoin quadruple therapy was more effective with metronidazole-sensitive strains (88%; 15 out of 17) than with metronidazole-resistant strains (33%; three out of nine; P=0.008). Two of the treatment failures had pre-treatment isolates susceptible to metronidazole, which were resistant after therapy.. Because nitrofurantoin quadruple therapy performed inadequately in the presence of metronidazole resistance, we conclude that nitrofurantoin is unlikely to find clinical utility for the eradication of H. pylori.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Anti-Ulcer Agents; Bismuth; Breath Tests; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Nitrofurantoin; Omeprazole; Organometallic Compounds; Salicylates; Tetracycline; Treatment Outcome; Urea

The inflammatory process involving Helicobacter pylori-associated gastritis is thought to lead to epithelial damage and contribute to the development of gastric cancer. Evidence exists from animal and in vitro studies suggesting that tetracyclines have both anti-inflammatory and tissue-protectant effects unrelated to their antimicrobial activity. We attempted to modulate components of H. pylori's inflammatory process by: (i) eliminating the infection; (ii) using tetracycline to alter the host's reaction to the infection without reducing the bacterial load; and (iii) using calcium to counteract the effect of excessive dietary salt.. We conducted a 16-week placebo-controlled clinical trial with 374 H. pylori-associated gastritis patients randomly assigned to one of five groups: (1) triple therapy consisting of metronidazole, amoxicillin and bismuth subsalicylate for 2 weeks, followed by bismuth alone for 14 weeks; (2) calcium carbonate; (3) triple therapy and calcium carbonate; (4) tetracycline; or (5) placebo.. Subjects in the tetracycline and triple therapy groups, but not the calcium carbonate only group, showed a reduction in inflammation and epithelial damage vs. those in the placebo group, independent of a change in H. pylori density and other factors. Our results also indicate that epithelial damage may be affected by mechanisms independent of H. pylori density or inflammation.. The results are consistent with the hypothesis that tetracycline can decrease inflammation independent of a reduction in the bacterial load. More research is needed to investigate mechanisms leading to epithelial damage which are independent of H. pylori density and inflammation.

Topics: Adult; Aged; Amoxicillin; Antacids; Anti-Bacterial Agents; Bismuth; Calcium Carbonate; Drug Therapy, Combination; Epithelium; Female; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Male; Metronidazole; Middle Aged; Organometallic Compounds; Penicillins; Placebos; Risk Factors; Salicylates; Stomach Neoplasms; Tetracycline; Treatment Outcome

A controlled, randomized, double-blind study in Bangladeshi children (ages 4-36 mo) with acute diarrhoea was undertaken to determine whether bismuth subsalicylate (BSS) would prevent the development of persistent diarrhoea (PD) in young children. The children were randomized to two groups: 226 were given liquid oral BSS, (as Pepto-Bismol), 100 mg/kg/d for 5 d; 225 were given placebo of identical appearance. On admission to the study, the two groups were comparable both clinically and microbiologically. Rotavirus was found in 56% of all the children, and enterotoxigenic E. coli in 31% of a subsample studied. Children treated with BSS had less severe and less prolonged illness than those treated with placebo (p = 0.057). There was, however, no difference in the development of PD between the two groups (8% and 11%). Unexpectedly, patients treated with BSS gained significantly more weight (2.3%) than those treated with placebo (0.5%; p < 0.001) during the course of the study. No toxicity of BSS was detected.. Treatment with BSS had a modest therapeutic effect on acute diarrhoea, as has been previously demonstrated, but with no suggestion of a therapeutic effect on the prevention of persistent diarrhoea in this group of patients.

Topics: Acute Disease; Bismuth; Child, Preschool; Diarrhea; Double-Blind Method; Escherichia coli Infections; Humans; Infant; Organometallic Compounds; Rehydration Solutions; Retroviridae Infections; Salicylates

ORS has led to improved outcome of acute gastroenteritis in both industrialised and developing countries. In both settings there is an increasing demand for active therapy to reduce the duration of diarrhoea and its complications. Persistent diarrhoea is a major consequence of intestinal infections and is responsible for a high number of deaths in poor countries. Bismuth subsalicylate has been used for treatment of acute diarrhoea, with preliminary promising results. In this issue of Acta Paediatrica, a trial with BSS is essential. However the results were marginal and did not justify a mass scale use of BSS, also because of poor cost efficacy rate.

Topics: Acute Disease; Bismuth; Child, Preschool; Diarrhea; Gastroenteritis; Humans; Infant; Organometallic Compounds; Rehydration Solutions; Salicylates

At present, the prevalence of Helicobacter pylori (H. pylori) in complicated peptic ulcer and the effect of H. pylori eradication on complicated peptic ulcer have not been fully established. In this study, we report the prevalence of H. pylori in peptic ulcer patients complicated with gastric outlet obstruction, effectiveness of oral eradication therapy on these patients, and their long-term follow up.. Ten consecutive patients presenting with clinically and endoscopically significant obstructed peptic ulcers were included in this study. During each endoscopy, seven gastric biopsy specimens were obtained and analyzed for H. pylori colonization.. The antral mucosal biopsy specimens were positive for H. pylori in nine patients. H. pylori infection was eradicated and complete ulcer healing was observed in all patients. The mean follow-up period was 14 (7-24) months. One patient had duodenal perforation and underwent surgical intervention following medical treatment, despite the eradication of H. pylori. Ulcer recurrence was noted in two (22.2%) of nine patients, and in one of them the recurrent ulcer was complicated with obstruction (11. 1%). The mean time to ulcer recurrence was 17 months (range, 10-24 months). The biopsies and CLOtests were H. pylori negative at the time of ulcer or erosion recurrence in two patients.. We suggest that H. pylori eradication may improve the resolution in obstructive ulcer cases with colonization.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Female; Follow-Up Studies; Gastric Outlet Obstruction; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Peptic Ulcer; Salicylates; Tetracycline; Treatment Outcome

In order to investigate the potential of Helicobacter pylori (HP) to induce dyspepsia, we performed a randomized prospective study on the long-term effect of HP-eradication on symptoms of HP-positive dyspeptic patients in whom other organic causes for dyspepsia were carefully ruled out.. 201 patients referred to our endoscopy unit with dyspeptic symptoms for at least six months entered the study. Patients with previous peptic ulcer were excluded.. After endoscopy of the upper alimentary tract and 13C-urea breath test, patients with active peptic ulcer, hiatal hernia, macroscopic evidence for esophagitis and negative HP-status were excluded. The remaining patients underwent abdominal sonography, H2-exhalation test with lactose, and 24-h pH monitoring in order to exclude other organic causes for dyspepsia. In 20 patients, dyspepsia was assumed to be due to HP-gastritis. Patients received eradication therapy and were controlled as assessed by the 13C-urea breath test six weeks and six months after completion of the therapy. Dyspeptic symptoms were monitored by means of a validated symptom score.. Out of 20 patients with HP-gastritis the first eradication treatment was successful in 13, while seven patients remained HP-positive after antibiotic treatment. Six months after completion of therapy the symptoms of HP-eradicated patients improved considerably (score values 17.4 +/- 1.5 and 10.2 +/- 0.8, respectively, p < 0.01) whereas symptoms of patients with persistent infection remained unchanged (21.1 +/- 1.7 and 20.4 +/- 1.5, n.s.) and only improved after successful retherapy (20.4 +/- 1.5 and 11.7 +/- 2.1, p < 0.05). In total, 17 of 20 patients (85%) improved after successful eradication. Also, neutrophil infiltration in the gastric mucosa correlated to both dyspeptic symptoms before therapy (r = 0.85) and the decrease in symptom score after HP-eradication (r = 0.61). In contrast, the symptoms of eight patients with gastroesophageal reflux disease were not improved after eradication (20.0 +/- 1.1 and 18.2 +/- 1.0, n.s.). HP-infection per se contributes to dyspepsia. 17 of 20 (85%) HP-positive dyspeptic patients improved after HP-eradication, when other potential organic causes for dyspepsia had been ruled out. However, many patients did not completely recover but the symptoms only partly decreased which parallels the persistence of part of the inflammatory infiltration in the gastric mucosa. This emphasizes the importance of HP-gastritis as an organic disease causing dyspeptic symptoms.

Topics: Adult; Aged; Amoxicillin; Anti-Ulcer Agents; Bismuth; Clarithromycin; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyspepsia; Female; Follow-Up Studies; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Salicylates; Tetracycline; Treatment Outcome

Metronidazole remains a key component of H. pylori infection therapy. It has been suggested that despite resistance, metronidazole may be effective when given at high dose with bismuth, tetracycline, and a proton pump inhibitor (quadruple therapy).. To prospectively evaluate metronidazole quadruple therapy for treatment of metronidazole resistant H. pylori infection in the United States.. Patients infected with metronidazole resistant H. pylori were prospectively prescribed 14 days of quadruple therapy consisting of metronidazole 500 mg t.d.s., tetracycline 500 mg q.d.s., two bismuth subsalicylate tablets q.d.s., and omeprazole 20 mg o.d.. A total of 26 patients were entered into the study; 22 for their first treatment and four as re-treatment for failed therapy. Of the 26 patients, 24 were cured (cure rate 92%; 95% CI: 78-99%). Both treatment failures reported full compliance to 14 days of therapy. Side-effects were common and resulted in premature discontinuation of therapy in 31%. Premature discontinuation did not reduce the cure rate.. Quadruple metronidazole combination therapy is effective despite the presence of metronidazole resistance and should be considered as either first line therapy or for failures of twice-a-day combination therapies.

Topics: Aged; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Omeprazole; Organometallic Compounds; Patient Compliance; Prospective Studies; Salicylates; Tetracycline; Treatment Outcome

Topics: Bismuth; Colitis; Humans; Organometallic Compounds; Salicylates

The mucus-bicarbonate barrier provides the first line of defense against potentially harmful gastric luminal contents. Its integrity can be assessed in man by demonstrating the presence of a pH gradient across the mucus gel layer, from the acidified lumen to near-neutral pH at the mucosa. Our aim was, firstly, to assess the effects of ethyl alcohol and bismuth subsalicylate on the integrity of this lumen-to-mucosal pH gradient and, secondly, to evaluate whether pretreatment with bismuth subsalicylate would protect against any deleterious effects of ethyl alcohol. Ten healthy adults underwent two upper endoscopic procedures with microelectrode measurement of juxtamucosal pH gradients. At the first endoscopy, the effects of 30 ml of bismuth subsalicylate on the gradient was evaluated. At the second endoscopy, gradients were measured before and after luminal installation of 60 ml of ethyl alcohol (40% v/v) and following pretreatment with either 30 ml of bismuth subsalicylate or placebo. pH measurements were technically easy to perform and provided consistently reproducible results. A distinct juxtamucosal pH gradient (pH 4.0 +/- 0.2 units) was identified in all subjects in the basal state. Neither bismuth subsalicylate nor ethyl alcohol had a significant effect on these gradients. We conclude that a distinct pH gradient between gastric luminal fluid and the mucus gel layer can be readily demonstrated in man. Neither bismuth subsalicylate nor ethyl alcohol have a significant effect on this gradient.

Topics: Adult; Bismuth; Ethanol; Female; Gastric Acid; Gastric Mucosa; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Organometallic Compounds; Salicylates

There have been a number of reports that natural foods such as garlic, honey, and capsaicin can inhibit Helicobacter pylori in vitro and each report has suggested the natural ingredient be used for treatment of the infection. We investigated whether garlic or capsaicin-containing peppers would actually inhibit H. pylori in vivo.. We performed a prospective crossover study in healthy H. pylori-infected adults. We used the urea breath test to assess the status of the H. pylori infection. On separate days subjects received three test meals consisting of beef, tortillas, and salad with one of the following: fresh garlic (10 sliced cloves), capsaicin (six sliced fresh jalapeños), two tablets of bismuth subsalicylate (Pepto-Bismol, positive control), or nothing added (negative control). Breath testing was done before the first meal, the evening meal, and the following morning. At least 2 days elapsed between the test substances.. Twelve subjects participated (seven men, five women), with an average age of 41.4 yr, range 27-51 yr. Ten subjects received garlic, six received jalapeños, and 11 received bismuth. Neither garlic nor capsaicin had any in vivo effect on H. pylori (median urease activity 28.5 vs 39.8 and 43.7 vs 46.6 before and after garlic and jalapeños, respectively) (p > 0.8). Bismuth had a marked inhibitory effect (median 55.8 vs 14.3 before and after bismuth) (p < 0.001), respectively.. This study did not support a role for either garlic or jalapeños in the treatment of H. pylori infection. Caution must be used when attempting to extrapolate data from in vitro studies to the in vivo condition.

Topics: Adult; Bismuth; Capsicum; Cross-Over Studies; Female; Garlic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Phytotherapy; Plants, Medicinal; Prospective Studies; Salicylates

To study the effects of treatment of Helicobacter pylori infection in a hyperendemic population, 143 infected patients from the region of Nariño, Colombia, were treated for 2 weeks with clarithromycin (500 mg twice a day), amoxicillin (1 g twice a day), and either lansoprazole (30 mg twice a day) or omeprazole (30 mg twice a day). All patients belong to a low socioeconomic strata, had multifocal atrophic gastritis documented by gastric biopsies, and had been treated previously and unsuccessfully for 2 weeks with bismuth subsalicylate (262 mg four times a day), amoxicillin (500 mg three times a day), and metronidazole (400 mg three times a day). 13C-urea breath tests were performed 6, 12, 24, and 60 weeks after completing therapy. The 13C-urea breath test was negative in 79.7% of patients 1 month after finishing therapy, and in 69.2% of patients 1 year after finishing treatment. There were no differences in eradication rates between patients treated with omeprazole versus lansoprazole. Dyspepsia symptoms decreased from 74% in patients at baseline to 19% at the time of finishing treatment. In low-socioeconomic status populations with hyperendemic infection, triple therapy using omeprazole or lansoprazole plus clarithromycin and amoxicillin is an effective alternative when previous standard bismuth-based triple therapy has failed.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Enzyme Inhibitors; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Penicillins; Proton Pump Inhibitors; Salicylates; Treatment Outcome

To determine whether an enhanced compliance program (ECP) improves patient compliance with bismuth subsalicylate, metronidazole, and tetracycline hydrochloride (BMT) triple therapy for the treatment of Helicobacter pylori infection and to identify factors that affect compliance with therapy.. A randomized controlled trial conducted in 4 staff-model health centers of a health maintenance organization in Massachusetts.. A total of 125 patients 18 years of age or older with peptic ulcer disease or dyspepsia whose clinicians prescribed BMT triple therapy for 14 days were randomized to a control group or to the ECP group. The ECP group received medication counseling (written and oral) from a pharmacist, along with a medication calendar and a minipillbox, as well as a follow-up telephone call after initiation of therapy. Compliance was assessed by a pill count, and factors affecting adherence to the regimen were identified by patients' reports.. There was no statistically significant difference between the 2 groups in the number of patients taking more than 60% of the medications (89% of the control group vs 95% of the ECP group; P>.30). However, there was a statistically significant difference in the number of patients taking more than 90% of the medications (67% of the control group vs 89% of the ECP group; P<.01). An intention-to-treat analysis confirmed these results. The most frequently reported adverse effect was gastrointestinal intolerance. Other factors reported to affect compliance included the frequency of dosing and the number of pills.. These findings suggest that although adverse effects were common, most patients were able to complete 60% or more of the 2-week regimen. An ECP further improved the percentage of medications taken.

Topics: Adult; Aged; Anti-Bacterial Agents; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Female; Health Maintenance Organizations; Helicobacter Infections; Helicobacter pylori; Humans; Male; Massachusetts; Metronidazole; Middle Aged; Organometallic Compounds; Patient Compliance; Program Evaluation; Salicylates; Tetracycline; Treatment Outcome

The pathogenesis of the microscopic colitis syndrome is unknown but may involve bacteria, an intestinal luminal antigen, and/or autoimmunity. It was hypothesized that bismuth subsalicylate would resolve both diarrhea and colonic inflammation in microscopic colitis because it possesses antidiarrheal, antibacterial, and anti-inflammatory properties.. Thirteen patients with microscopic colitis (7 with subepithelial collagen deposition and 6 without) were treated with eight chewable 262-mg bismuth subsalicylate tablets per day for 8 weeks. Patients recorded the frequency of bowel movements daily. Forty-eight-hour stool collections and flexible sigmoidoscopy with 24 biopsies were performed before and after treatment in each patient.. Twelve patients completed the trial. Eleven patients had a resolution of diarrhea and a reduction in fecal weight. The average time to respond was 2 weeks. In 9 patients, colitis resolved. When present before treatment, subepithelial collagen thickening disappeared. Those completing the trial experienced no side effects. Posttreatment follow-up for 7-28 months shows that 9 patients remain well having undergone no further treatment, 2 are well but required retreatment, and 1 has continued diarrhea.. Bismuth subsalicylate treatment for 8 weeks is safe and well tolerated. This regimen appears to be efficacious for the treatment of microscopic colitis and is worthy of further study in a controlled trial.

Topics: Administration, Oral; Adult; Aged; Bismuth; Colitis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Organometallic Compounds; Salicylates; Treatment Outcome

Clarithromycin is a new macrolide antibiotic which is known to be highly effective in eradicating Helicobacter pylori (H. pylori). In Chinese, the role of clarithromycin for H. pylori is still unclear.. Between January 1995 and February 1996, 75 patients with active H. pylori-positive duodenal ulcer were enrolled in this study. Three groups were randomized to have (1) 2 x 150 mg nizatidine twice daily, 2 x 250 mg amoxicillin four times daily, and 2 x 250 mg clarithromycin three times daily for two weeks (niz-amox-clar group, N = 25); or (2) 20 mg omeprazole twice daily plus 2 x 250 mg clarithromycin three times daily for two weeks (ome-clar group, N = 25); or (3) 300 mg bismuth subsalicylate four times daily, and 2 x 250 mg amoxicillin four times daily, 250 mg metronidazole four times daily for two weeks (triple therapy group, N = 25). All the patients received H2 receptor antagonist (150 mg nizatidine or ranitidine, or 400 mg cimetidine, twice daily) for the consecutive six weeks.. The eradication rate of H. pylori eight weeks after the entry of study was 80%(20/25) in the niz-amox-clar group, 76%(19/25) in the ome-clar group, 88%(22/25) in the triple therapy group (p < 0.05 among the three groups). The ulcer healing rates eight weeks after the entry of study for the niz-amox-clar, the ome-amox, and the triple therapy groups were 84%(21/25), 80%(20/25), and 80%(20/25), respectively (p < 0.05 among the three groups). The number of patients experiencing adverse effects in the niz-amox-clar group, the ome-clar group, and the triple therapy group were 10(40%), 7(28%), and 4(16%), respectively (p > 0.05 among the three groups).. Both nizatidine/amoxicillin/clarithromycin and omeprazole/clarithromycin regimens can achieve good eradication rates and may provide an effective alternative anti-H. pylori treatment in duodenal ulcer diseases.

Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Metronidazole; Middle Aged; Nizatidine; Omeprazole; Organometallic Compounds; Penicillins; Ranitidine; Salicylates

We evaluated the efficacy of lansoprazole, clarithromycin, and metronidazole (LCM) administered twice daily for 7 days. Because there is growing concern about the development of metronidazole-resistant H. pylori (HP) strains, we also tested a novel regimen consisting of lansoprazole, clarithromycin, and bismuth subsalicylate (LCB).. Patients with active HP infection and peptic ulcer, a history of peptic ulcer, or nonulcer dyspepsia were randomized to either lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d. or lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and bismuth subsalicylate 524 mg b.i.d. (LCB) for 7 days. Compliance and side effects were recorded by using a diary.. "Per protocol" eradication with LCM was achieved in 41 of 47 (87%). By using "intention to treat" analysis, LCM eradicated HP infection in 43 of 53 patients (81%). By using "per protocol" analysis, LCB eradicated HP infection in 40 of 47 patients (85%). On an "intention to treat" basis, LCB led to HP eradication in 42 of 52 (81%). The most common significant side effects observed with LCM were altered taste (39%) and abdominal pain (19%). With LCB, the most common significant side effects were altered taste (23%) and dark stools (23%).. LCB for 7 days was as effective in eradicating HP infection as a 7-day course of LCM. Further studies evaluating the role of bismuth compounds in proton-pump inhibitor based triple therapy are warranted. Such therapy may have particular importance in areas where high metronidazole resistance is a concern.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Abdominal Pain; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Clarithromycin; Drug Administration Schedule; Drug Combinations; Drug Resistance, Microbial; Dyspepsia; Evaluation Studies as Topic; Feces; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Medical Records; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Patient Compliance; Peptic Ulcer; Proton Pump Inhibitors; Salicylates; Taste Disorders

Quadruple therapy (bismuth, metronidazole and tetracycline (BMT) + proton pump inhibitor) is touted as being > 95% effective, regardless of metronidazole resistance. We tested a 10-day b.d. quadruple therapy for treatment of H. pylori infection.. Anti-H. pylori therapy consisted of lansoprazole 15 mg b.d. plus tetracycline 500 mg b.d., metronidazole 500 mg b.d., and swallowable Pepto-Bismol caplets (2 b.d.) for 10 days. H. pylori status was evaluated by culture and histology before and 4 or more weeks after therapy.. The cure rate for intention-to-treat was 70%. Treatment success was calculated overall and separately in relation to antimicrobial resistance patterns. The cure rate among the metronidazole-sensitive isolates was 89.7% (26 of 29) vs. 41.2% (7 of 17) of the metronidazole-resistant isolates (P < 0.005). Moderate (n = 1) or severe (n = 3) side-effects were experienced in four patients with only one withdrawing because of side-effects.. Twice a day quadruple therapy is effective for metronidazole-sensitive strains but its usefulness is markedly reduced by the presence of pre-treatment metronidazole resistance. Twice a day quadruple therapy can be recommended in locations where background metronidazole resistance is uncommon. Possibly, 14-day therapy or a higher dosage of metronidazole provide better results with metronidazole-resistant H. pylori.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Enzyme Inhibitors; Female; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Proton Pump Inhibitors; Salicylates; Smoking; Tetracycline; Tetracyclines

In an attempt to increase the efficacy and simplicity of FDA-approved regimens for Helicobacter pylori, we studied (1) addition of an inexpensive antibiotic (amoxicillin) to twice-daily ranitidine bismuth citrate (RBC)-clarithromycin dual therapy, and (2) substitution of RBC for bismuth subsalicylate + H2-receptor antagonist in bismuth-based triple therapy.. Subjects with previously untreated Helicobacter pylori infection documented by 13C-urea breath test plus either endoscopic biopsy or serology were randomly assigned to a 2-wk course of (1) RBC 400 mg b.i.d., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d. (RAC), or (2) RBC 400 mg b.i.d., metronidazole 250 mg t.i.d., and tetracycline 500 mg t.i.d. (RMT). Repeat breath test was performed 4 wk after the completion of therapy.. Intent-to-treat and per-protocol cure rates for RAC were 46 of 50 patients (92%) and 45 of 47 patients (96%); for RMT they were 40 of 50 patients (80%) and 37 of 42 patients (88%). Study drugs were stopped due to side effects in three patients (6%) taking RAC and six patients (12%) taking RMT.. Twice-daily RBC-based triple therapy with clarithromycin and amoxicillin produces Helicobacter pylori eradication rates over 90%, which is comparable to rates seen with proton pump inhibitor-based triple therapies. RBC also may be substituted for bismuth subsalicylate and an + H2-receptor antagonist in standard bismuth-based triple therapy.

Topics: Adult; Amoxicillin; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Biopsy; Bismuth; Breath Tests; Carbon Isotopes; Clarithromycin; Drug Combinations; Female; Follow-Up Studies; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Metronidazole; Organometallic Compounds; Penicillins; Peptic Ulcer; Proton Pump Inhibitors; Ranitidine; Salicylates; Tetracycline; Urea

Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. Since gastric cancer is common in Peru, eradication of H. pylori may help to reduce the occurrence of gastric cancer. This study involved three randomized trials to determine the efficacy of four different triple-drug therapy regimens. The most successful regimen was furazolidone combined with bismuth subsalicylate and amoxicillin, which eradicated infection in 82% of patients. Patients successfully treated were followed every 2-3 months to determine the recurrence rate of H. pylori infection. Of 105 patients with H. pylori eradication documented by pathology and culture, 52% (55) returned for follow-up endoscopy, and in 73% (40) of these 55 the infection recurred during the 8-month follow-up period. Thirty-five patients from whom H. pylori was eradicated and who were tested for antibodies to H. pylori remained consistently seropositive. Rapid recurrence of H. pylori infection after successful eradication suggests that measures other than antimicrobial therapy are needed to fight H. pylori in developing countries.

Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Female; Follow-Up Studies; Furazolidone; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Peru; Recurrence; Salicylates; Tetracycline; Tinidazole

Bismuth subsalicylate, tetracycline hydrochloride, and metronidazole are widely used in combination for the treatment of Helicobacter pylori infections. As a result, there is renewed interest in the interaction between tetracycline and bismuth subsalicylate.. To determine whether the observed decrease in tetracycline bioavailability is due to the active drug bismuth subsalicylate via complexation, or to magnesium aluminum silicate (Veegum), an inactive excipient present only in the liquid formulation of bismuth subsalicylate, which might adsorb the tetracycline, rendering it unavailable for systemic absorption.. Eleven healthy volunteers participated in a randomized three-period, three-treatment complete crossover study with a 7-day washout interval between treatments. After an overnight fast, subjects received a 500-mg capsule of tetracycline hydrochloride with either tap water, 30 mL of bismuth subsalicylate (525 mg) liquid containing Veegum (Pepto-Bismol), or 30 mL of a specially formulated bismuth subsalicylate (525 mg) liquid without Veegum. Blood was collected for 24 hours after each dose of tetracycline. Serum was assayed for tetracycline concentration by HPLC. In addition, standard in vitro ultraviolet spectrophotometric methods were used to determine the capacity for complexation of bismuth with tetracycline and for adsorption of tetracycline to Veegum.. Compared with the reference treatment of tetracycline hydrochloride with water, the liquid formulation of bismuth subsalicylate containing Veegum decreased the maximum serum concentration (Cmax) of tetracycline by 21% and the serum tetracycline AUC by 27% (p < 0.001). The bismuth subsalicylate formulation without Veegum resulted in decreases in Cmax and AUC of 11% and 13%, respectively (p > 0.05 vs. tetracycline hydrochloride with water). Multiple linear regression analysis of the spectral absorbance data demonstrated a calculated recovery of tetracycline of 100.9% and, therefore, a lack of in vitro complexation with bismuth. At pH 1.2, the amount of tetracycline adsorbed to Veegum ranged from 91.5% to 97.2% over the concentration range of 0.25 to 2 mg/mL. At pH 7.0, the values ranged from 82.9% to 83.9% over the concentration range of 0.25 to 1 mg/mL.. In vitro and in vivo data from this study indicate that Veegum, a suspending agent, and not the active agent bismuth subsalicylate, is the primary ingredient in liquid formulations of bismuth subsalicylate responsible for a decrease in tetracycline bioavailability. In addition, the mechanism of interaction is not likely due to complexation between tetracycline and bismuth subsalicylate, as previously postulated, but rather is caused by adsorption of tetracycline to the excipient Veegum, which is present only in the liquid formulation of bismuth subsalicylate. The clinical relevance of this interaction has not been determined.

Topics: Adolescent; Adult; Aluminum Compounds; Antacids; Biological Availability; Bismuth; Chromatography, High Pressure Liquid; Cross-Over Studies; Female; Humans; Intestinal Absorption; Magnesium Compounds; Male; Middle Aged; Organometallic Compounds; Regression Analysis; Salicylates; Silicates; Tetracycline

To assess the effect of aluminum hydroxide/magnesium hydroxide antacid and bismuth subsalicylate on gastric pH in clinically normal horses and to develop guidelines on the use of these agents for treatment of peptic ulcer disease in horses.. Prospective, randomized, controlled trial.. 5 clinically normal adult horses with chronically implanted gastric cannulas.. Each horse received all 5 treatments (30 g of aluminum hydroxide/15 g of magnesium hydroxide, 12 g of aluminum hydroxide/6 g of magnesium hydroxide, 10.5 g of bismuth subsalicylate, 26.25 g of bismuth subsalicylate, and 5% methylcellulose control) with only 1 experiment performed each day. Gastric pH was measured via a glass electrode inserted through the gastric cannula for 1 hour before treatment and continued for 2 hours after treatment. Food or water was not given to the horses during the experiment. Measurements of gastric pH obtained during posttreatment hours were compared with pretreatment gastric pH values.. Only a dose of 30 g of aluminum hydroxide/ 15 g of magnesium hydroxide resulted in a significant increase in gastric pH over baseline or control values. Mean pH was 5.2 +/- 0.62 and 4.59 +/- 0.48 for posttreatment hours 1 and 2, respectively.. Oral administration of 30 g of aluminum hydroxide/15 g of magnesium hydroxide to adult horses should result in a mean hourly gastric pH > or = 4.0 for at least 2 hours.

Topics: Administration, Oral; Aluminum Hydroxide; Animals; Antacids; Bismuth; Drug Therapy, Combination; Female; Gastric Acidity Determination; Gastric Mucosa; Horse Diseases; Horses; Hydrogen-Ion Concentration; Magnesium Hydroxide; Male; Organometallic Compounds; Peptic Ulcer; Prospective Studies; Salicylates; Stomach

We studied prospectively in a single-blind controlled manner the efficacy of 4-wk triple-antibiotic therapy, with amoxicillin (500 mg p.o., t.i.d.), metronidazole (250 mg p.o., t.i.d.), and bismuth subsalicylate tablets (524 mg p.o., q.i.d.), plus omeprazole (20 mg p.o., q.d.) and compared it with omeprazole (id) in the treatment of duodenal ulcer (DU) patients colonized with Helicobacter pylori.. One hundred DU patients were entered prospectively over a 12-month period. Fifty-seven of them received triple therapy plus omeprazole and 43 received omeprazole alone. Clinical, endoscopic, and bacteriological evaluations were performed on admission and at 28 days, 4, 8, and 12 months after treatment.. After 4-wk treatment (day 28), the ulcer healing rate was high, but there was no significant difference between rates in the triple therapy and omeprazole groups (99% vs. 91%). In contrast, the long-term DU recurrence rate after 12-month follow-up was significantly lower (p > 0.01) for triple therapy (3/57, 5%), compared with omeprazole (34/43, 79%). The difference (higher relapse rate for omeprazole-treated patients) was significant (p < 0.001) by the second evaluation, 4 months after treatment. The eradication rate of H. pylori was also significantly higher among DU patients treated with triple therapy (p < 0.001) during all prospective evaluations, grand mean, 82% (range 82-87%), compared with the omeprazole-treated group, in which there were no cases in which H. pylori was eradicated. Follow-up revealed that 2/47 H. pylori-eradicated patients became reinfected after 1 yr, giving a reinfection rate of 4.2 patient/yr.. Four-week triple-antibiotic therapy plus omeprazole constitutes an adequate alternative for treatment of Chilean DU patients.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anti-Ulcer Agents; Bismuth; Chile; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Penicillins; Prospective Studies; Recurrence; Salicylates; Single-Blind Method; Time Factors

Helicobacter pylori infection is associated with gastric ulcer disease in about 75% of cases.. The aim of this study was to determine whether H. pylori eradication reduces gastric ulcer relapse rates.. The study was randomized, controlled, multicentric and investigator blinded, and was conducted at three university hospitals, two teaching hospitals, and by six practising gastroenterologists.. During a period of 1 year 152 patients with gastric ulcers were randomly assigned to one of two treatment regimens: omeprazole 20 mg daily in the morning for 8 weeks (74 patients), or bismuth subsalicylate 600 mg three times daily for 8 weeks combined with 500 mg amoxicillin twice daily and 1000 mg tinidazole twice daily for the first 10 days (triple therapy) (78 patients). Follow-up examinations were performed 6, 12 and 18 months after treatment and whenever ulcer symptoms occurred.. Of the 152 randomized patients five were excluded because of gastric cancer, 10 missed follow-up examinations and seven receiving triple therapy terminated treatment because of side effects. Of the remaining 130 patients, five of 69 (7.2%) in the omeprazole and six of 61 (9.8%) in the triple group were H. pylori negative. After 8 weeks' therapy, the gastric ulcer was healed in 85.9% (omeprazole) and in 81.8% triple) in H. pylori-positive patients, and in 80% (omeprazole) and 16.7% (triple) in H. pylori-negatives. H. pylori was eradicated in 8.1% of the patients who received omeprazole monotherapy and in 78.2% receiving triple therapy, and in 8.1% and 69.4% in an intention-to-treat analysis. The subsequent relapse rates during a follow-up period of 12 months were 50% in the omeprazole group and 4% in the triple group. Gastric ulcer relapse was observed in 49% of patients who were H. pylori positive and in 2% who were H. pylori negative after treatment.. The data show that the presence of H. pylori is an important predictor of gastric ulcer relapse and that eradication of H. pylori may heal gastric ulcer disease.

Topics: Adult; Aged; Amoxicillin; Anti-Ulcer Agents; Biopsy; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Omeprazole; Organometallic Compounds; Penicillins; Recurrence; Salicylates; Stomach Ulcer; Time Factors; Tinidazole

In clinical practice, eradication of Helicobacter pylori infection may be difficult due to medication side effects and the need for 2 weeks of therapy. Because therapies of shorter duration may improve patient compliance and reduce treatment side effects, we compared the efficacy and tolerability of two anti-H. pylori treatments of 1 week's duration. Patients with H. pylori infection were randomized to treatment with either (a) short-course triple therapy, composed-of bismuth subsalicylate (Pepto-Bismol, Procter & Gamble, Cincinnati, OH, U.S.A.) two tablets four times daily, amoxicillin 1 g (two 500-mg tablets) twice daily, and metronidazole 500 mg four times daily on days 5-7 or (b) omeprazole 40 mg twice a day with amoxicillin 1 g twice a day for 1 week. At least 4 weeks posttreatment, efficacy was evaluated with either histological evaluation of antral biopsies for H. pylori or 14C urea breath testing. Patients who failed initial therapy were allowed to cross over to the alternative treatment regimen after a minimum "wash-out" period of 5 weeks. Patients completed a diary during therapy to monitor both compliance and side effects. Thirty-four patients completed the study, 10 receiving both treatment regimens. Treatment with the shortcourse triple therapy eradicated H. pylori in 78.3% of treatments compared with 38% with the high-dose omeprazole/ amoxicillin combination (p < 0.05). Patients were highly compliant with both treatments, and mild side effects, such as transient loose stools or abdominal pain, were common in both groups. This is the first report from North America confirming the success of the short-course triple therapy for the eradication of H. pylori. The high-dose omeprazole/ amoxicillin regimen's eradication rate was markedly inferior to that achieved by the short-course triple therapy regimen and should not be used. Comparative studies of the short-course triple therapy regimen with other 7-day anti-H. pylori treatment regimen therapies are indicated.

Topics: Amoxicillin; Anti-Ulcer Agents; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Penicillins; Salicylates

The present study was designed to compare the efficacy and tolerability of triple therapy and dual therapy for Helicobacter pylori in duodenal ulcer patients and to evaluate the long-term clinical course of ulcer disease. Forty duodenal ulcer patients with proven H. pylori infection were enrolled into the study and randomly treated with either triple therapy consisting of bismuth subsalicylate, metronidazole and tetracycline plus ranitidine or with dual therapy comprising omeprazole and amoxicillin. Patients were investigated clinically and endoscopically including assessment of H. pylori infection by means or rapid urease test, culture, histology and urea breath testing 4 weeks after cessation of eradication therapy, in 1-year intervals and when dyspeptic symptoms recurred. One patient of each group was lost during follow-up. H. pylori infection was cured by triple therapy in 84.2% and by dual therapy in 78.9% (p = 1.00). During follow-up, all patients with cure of H. pylori infection (n = 31) remained in stable remission with respect to duodenal ulcer disease, while 6 out of 7 patients persistently infected with H. pylori developed an ulcer relapse (p < 0.001). One patient with cured infection had had an episode of dyspeptic symptoms requiring pharmacotherapy and in another 3 patients mild refluxesophagitis without necessity of medical treatment had been detected on the occasion of a scheduled endoscopy. In the short-term, cure of the infection resulted in a marked reduction of the degree of antral gastritis and in a loss of activity in all but one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Duodenal Ulcer; Female; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Penicillins; Prospective Studies; Ranitidine; Recurrence; Salicylates; Tetracycline; Treatment Outcome

It remains controversial whether Helicobacter pylori infection causes symptoms in non-ulcer dyspepsia. One hundred non-ulcer dyspepsia patients were screened for H. pylori infection between November 1989 and February 1994. Forty patients entered a trial where both infected and uninfected patients were treated with H. pylori therapy, with the uninfected group serving as controls.. Non-ulcer dyspepsia was defined as unexplained epigastric discomfort lasting for at least 4 wk. From November 1989 until February 1992, all patients, regardless of H. pylori status, were treated with bismuth subsalicylate tablets (524 mg q.i.d.) for 4 wk and metronidazole (250 mg q.i.d.) for the first 2 of the 4 wk. From March 1992 until February 1994, only infected patients were treated in an attempt to obtain equal numbers in each group. H. pylori infection was diagnosed histologically at the index endoscopy and 1 month after completion of therapy. Symptoms were scored on a 0-5 scale for both frequency and severity.. Of 100 patients screened, 33 were infected with H. pylori (mean age, 42; 10 men, 23 women), and 67 were uninfected (mean age, 38; 16 men, 51 women). Thirty-six uninfected patients were not offered treatment during the latter part of the trial. Of the remaining 31 uninfected patients, 10 dropped out; of the 33 infected patients, 14 dropped out. Twenty-one uninfected patients and 19 H. pylori-infected patients completed treatment; in 13 of 19 patients (68%), H. pylori was eradicated. Symptoms improved in eight of 13 (61%) H. pylori-eradicated patients and in four of six (66%) H. pylori-persistent patients, compared with 14 of 21 (66%) uninfected patients. Long-term follow-up (mean, 34 months) showed similar symptom outcome in the two treatment groups.. Thirty-three percent of our non-ulcer dyspepsia patients were infected with H. pylori, a number similar to the percentage of infected age-matched controls in the U.S. Treatment with bismuth subsalicylate and metronidazole resulted in symptomatic improvement in 61-66% of non-ulcer dyspepsia patients regardless of initial or post-treatment H. pylori status. Long-term symptom follow-up in both the control and infected groups gave similar results. H. pylori infection is not related to the symptoms of non-ulcer dyspepsia.

Topics: Adult; Bismuth; Drug Therapy, Combination; Dyspepsia; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Organometallic Compounds; Salicylates; Time Factors

Azithromycin is new acid-stable macrolide that achieves 10- to 40-fold higher tissue levels than erythromycin after oral dosing. Important to note, the tissue half-life of azithromycin is measured in days instead of hours.. We evaluated two new triple therapies for Helicobacter pylori infection in which azithromycin was substituted for metronidazole either as 250 mg b.i.d. or t.i.d. along with tetracycline 500 mg q.i.d. and bismuth subsalicylate 2 tablets q.i.d. for 14 days. H. pylori status was determined by histology before and 6 wk or more after therapy.. Thirty men with documented H. pylori peptic ulcers completed therapy. Twenty-one also received ranitidine (300 mg in the evening) along with the antimicrobial therapy. H. pylori infection was successfully treated in 15 (50%) (95% CI = 31-69%). The cure rate was significantly higher with the 250-mg-t.i.d.-azithromycin dosage regime (83%) (95% CI = 52-98%) compared to the 250-mg-b.i.d.-dosage regime (28%) (95% CI = 10-53%) (p < 0.01). Troublesome side effects were experienced by the majority of those receiving azithromycin t.i.d.. We conclude that although 750 mg or more of azithromycin might eventually be able to replace metronidazole or clarithromycin in standard triple therapy, additional studies are required to identify a regime that is both effective and tolerable.

Topics: Azithromycin; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Peptic Ulcer; Ranitidine; Salicylates; Tetracycline

Chronic Helicobacter pylori-associated gastritis is now widely accepted as one of the most important pathogenic factors in duodenal ulcer disease. However, little is known about for how long patients remain free of duodenal ulcer relapses after H. pylori infection has been cured. In the present study, we investigated remission time during a 5-year follow-up period after anti-H. pylori treatment.. The patients were randomly allocated to treatment with either a combination of 3 x 600 mg bismuth subsalicylate and 2 x 1000 mg amoxycillin or 3 x 600 mg bismuth subsalicylate monotherapy. Endoscopy, including histological and microbiological examination of biopsies, was performed 4 weeks after termination of treatment and after 1 and 2 years. During the third, fourth and fifth years of the follow-up period, patients were monitored twice a year for symptoms compatible with ulcer relapse and for their use of anti-ulcer medication. Endoscopic and histological examinations were carried out whenever symptoms occurred.. Of 56 evaluated patients, 47 showed healing of ulcers after bismuth subsalicylate plus amoxycillin compared with 44 of 57 after bismuth subsalicylate monotherapy. H. pylori infection was cured in 52% (29 of 56) of the patients after combined therapy and in 4% (2 of 57) after the monotherapy. The cumulative duodenal ulcer relapse rates after 5 years were 38% (18 of 47) after the combined therapy and 75% (33 of 44) after the monotherapy. In patients who were cured of H. pylori infection, the cumulative duodenal ulcer relapse rate after 5 years was 9.7% (3 of 31), compared with 81.7% (49 of 60) in those patients who remained H. pylori-positive after treatment (P < 0.001). In two of the three patients who suffered duodenal ulcer relapse after being cured of H. pylori infection, H. pylori was present again at the time of relapse.. The data suggest that curing H. pylori infection results in long-term cure of duodenal ulcer disease and that duodenal ulcer relapses in successfully treated patients are most often associated with H. pylori reinfection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Bismuth; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Duodenal Ulcer; Female; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Penicillins; Recurrence; Salicylates

A single oral dose of 528 mg of bismuth subsalicylate (30 ml of Pepto-Bismol) had no significant effect on the plasma pharmacokinetics of a single oral dose of 750 mg of ciprofloxacin administered to 12 healthy volunteers (six men and six women). These results suggest that ciprofloxacin bioavailability will not be significantly decreased by single doses of bismuth subsalicylate when the two medications are administered simultaneously.

Topics: Absorption; Administration, Oral; Adult; Biological Availability; Bismuth; Ciprofloxacin; Cross-Over Studies; Drug Interactions; Female; Humans; Male; Organometallic Compounds; Salicylates

Topics: Bismuth; Diarrhea, Infantile; Dietary Fiber; Egypt; Gastrointestinal Agents; Humans; Infant; Male; Organometallic Compounds; Salicylates; Silicates

We evaluated whether therapy designed to eradicate Helicobacter pylori infection resulted in a reduction in rebleeding in patients with peptic ulcer disease. Patients presenting because of major upper gastrointestinal hemorrhage from peptic ulcer and whose ulcers healed in a study in which they were randomized to receive ranitidine alone or triple therapy plus ranitidine were followed up regularly with endoscopy. No maintenance anti-ulcer therapy was given after ulcer healing.. Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet), and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given. Development of ulcer recurrence with or without recurrent upper gastrointestinal bleeding was evaluated.. Thirty-one patients with major upper gastrointestinal bleeding from peptic ulcer were studied; 17 received triple therapy and 14 ranitidine alone. Major rebleeding occurred significantly (p = 0.031) more often in those in the ranitidine group (28.6%), compared with none (0%) in the triple therapy group.. Eradication of H. pylori infection reduces the rate of ulcer recurrence and rebleeding in complicated ulcer disease.

Topics: Adult; Aged; Bismuth; Drug Therapy, Combination; Follow-Up Studies; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Peptic Ulcer; Prospective Studies; Ranitidine; Recurrence; Salicylates; Tetracycline

Gastritis caused by Helicobacter pylori (HP) is common in patients with nonulcer dyspepsia (NUD), but an etiologic relationship between the histologic lesion and clinical symptoms is unproven. HP is inhibited by bismuth subsalicylate (BSS), a traditional remedy for dyspeptic complaints. The aim of this study was to assess the short- and long-term effects of BSS on HP, gastritis, and symptoms in patients with NUD. One hundred twenty-six patients with NUD who were shown to be infected with H. pylori (HP+) were enrolled. There was a two-week placebo run-in period to eliminate placebo responders. Fifty patients remained symptomatic and were randomly assigned to therapy with either BSS liquid or a matching placebo. EGD, biopsy, and clinical evaluations were performed at entry, at week 5 (end of therapy), at week 9 (four weeks after therapy), or at time of symptomatic relapse. Twenty-seven patients received placebo and 23 patients received BSS. BSS suppressed H. pylori in 15/23 patients (65%) and eradicated it in one patient, whereas the placebo had no effect on H. pylori. Gastritis improved during therapy with BSS but relapsed by week 9. There was no significant change in level of dyspeptic symptoms during or after treatment, although one month after the end of treatment, the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured. The study confirms that BSS given for three weeks suppresses but does not usually eradicate H. pylori. Such short-term suppression of H. pylori heals gastritis but does not result in clinical improvement.

Topics: Adult; Bismuth; Chronic Disease; Double-Blind Method; Dyspepsia; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Leukocyte Count; Organometallic Compounds; Salicylates; Treatment Outcome

Treatment with amoxicillin and omeprazole resulted in encouraging Helicobacter pylori eradication rates in pilot studies that included medium term follow up. These results were evaluated in a prospective, randomised and controlled study. Forty patients with active duodenal ulcer disease and H pylori colonisation of the gastric mucosa were randomly assigned to receive either omeprazole (20 mg twice daily) and amoxicillin suspension (500 mg four times daily) for two weeks (group I) or bismuth subsalicylate (600 mg three times daily), metronidazole (400 mg three times daily), tetracycline (500 mg three times daily), and ranitidine (300 mg in the evening) for two weeks (group II). Study medication was followed in both groups by a four week treatment course with 300 mg ranitidine up to the final examination. One patient from each group was lost to follow up. H pylori was eradicated in 78.9% of group I and 84.2% of group II (p = 1.00). All ulcers in patients on omeprazole plus amoxicillin healed but in the triple treatment group four patients had residual peptic lesions after six weeks (ulcer healing rate: 78.9%, p = 0.11). Complete pain relief occurred after a median duration of 1 day in group I and of 6 days in group II (p = 0.03). There were no major complications in either group but minor side effects were more frequently recorded in patients on triple therapy (63.2% v 15.8%, p < 0.01). In conclusion, two weeks of treatment with omeprazole plus amoxicillin is as good as triple therapy plus ranitidine in eradicating H pylori but seems better with regard to safety, pain relief, and ulcer healing. Thus, amoxicillin plus omeprazole should be recommended as the treatment of choice in eradicating H pylori in patients with duodenal ulcer disease.

Topics: Adult; Aged; Amoxicillin; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Prospective Studies; Salicylates; Tetracycline

Triple therapies using bismuth, metronidazole and tetracycline or amoxicillin were the first truly successful anti-H. pylori therapies. Metronidazole resistance has become an increasing problem that has severely limited the usefulness of the original triple therapy. Resistance to tetracycline or amoxicillin has not been reported and both are effective against H. pylori. We therefore tested a new triple therapy consisting of 500 mg tetracycline, 500 mg amoxicillin, and 2 tablets of bismuth subsalicylate each administered four times daily (with meals and at bedtime) for 14 days during treatment with ranitidine 300 mg daily. H. pylori eradication was defined as no evidence of H. pylori one or more months after stopping therapy. H. pylori status was evaluated by a combination of urea breath test and histology. Sixteen patients with H. pylori infection and active peptic ulcers were enrolled. The new triple therapy was successful in only 7 individuals (43%). Metronidazole appears to be critical for the effectiveness of the original triple therapy. An alternative to metronidazole will be required for a new successful triple therapy.

Topics: Adult; Aged; Amoxicillin; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Stomach Ulcer; Tetracycline

Bismuth subsalicylate is a common constituent of over-the-counter medications for diarrhea. However, it is uncertain whether bismuth offers any more benefit than standard oral rehydration therapy with early feeding.. We conducted a placebo-controlled, randomized trial to evaluate the effect of bismuth subsalicylate (100 or 150 mg per kilogram of body weight per day for up to 5 days) on the duration and volume of acute watery diarrhea in 275 male infants and young boys (mean age, 13.5 months). Serum salicylate and bismuth levels were monitored throughout the study and were also measured two weeks after discharge. All the patients received fluid replacement by the oral route and early feeding of easily digestible foods with high caloric density.. Diarrhea stopped within 120 hours of admission in 74 percent of the patients given placebo, 89 percent of those given 100 mg of bismuth per kilogram (P = 0.009 vs. the placebo group), and 88 percent of those given 150 mg of bismuth per kilogram (P = 0.019 vs. the placebo group). As compared with the patients given placebo, those given bismuth had significant reductions in their total stool output (P = 0.015), total intake of oral rehydration solution (P = 0.013), and duration of hospitalization (P = 0.005); there was no significant difference between the two groups given bismuth in these clinical outcomes. All measurements of bismuth and salicylate concentrations in blood were well below concentrations considered toxic. No adverse reactions were seen.. Treatment with bismuth subsalicylate decreases the duration of diarrhea and is a safe and effective adjunct to oral rehydration therapy for infants and young children with acute watery diarrhea.

Topics: Acute Disease; Bismuth; Body Weight; Chemotherapy, Adjuvant; Child, Preschool; Diarrhea, Infantile; Double-Blind Method; Fluid Therapy; Humans; Infant; Male; Multivariate Analysis; Organometallic Compounds; Salicylates

Fifty nine patients with Helicobacter pylori positive duodenal ulcers that failed to heal after a six week course of treatment with H2 blockers were randomly assigned to one of the following three regimens: (i) bismuth subsalicylate, 600 mg three times daily (n = 19), (ii) ranitidine, 300 mg at night (n = 20), (iii) bismuth subsalicylate plus ranitidine (n = 20). Cumulative ulcer healing rates after four and eight weeks respectively were as follows: bismuth subsalicylate 74% (14/19) and 95% (18/19), ranitidine 40% (8/20) and 65% (13/20), bismuth subsalicylate plus ranitidine 80% (16/20) and 95% (19/20). Bismuth subsalicylate treatment was better than ranitidine at both four and at eight weeks (p less than 0.05). The clearance rates for H pylori after four weeks were: bismuth subsubsalicylate 58%, ranitidine 0%, bismuth subsalicylate plus ranitidine 55%. After stopping bismuth therapy bacterial recrudescence frequently occurred. After bismuth treatment 86% (19/22) of ulcers had healed if H pylori had been cleared, whereas only 65% (11/17) had healed if H pylori persisted (NS). This study shows that bismuth subsalicylate is more effective in the treatment of resistant duodenal ulcers than standard dose ranitidine. It may be that suppression of H pylori by bismuth subsalicylate promotes ulcer healing.

Topics: Bismuth; Drug Resistance, Microbial; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Middle Aged; Organometallic Compounds; Ranitidine; Salicylates; Time Factors

We evaluated clindamycin and bismuth subsalicylate (Pepto-Bismol) for treatment of Helicobacter pylori infection. Patients with culture or histology positive for H. pylori were randomized to receive two tablets of bismuth subsalicylate four times daily for 4 weeks or bismuth combined with 2 weeks of 300 mg clindamycin four times daily. Clinical symptoms were recorded before and after treatment by means of visual analog scales. Patients in both treatment arms showed improvement in clinical scores for abdominal pain, heartburn, and gas or bloating. Microbiologic cure was achieved in only 1 of 11 patients treated with bismuth alone and in none of 7 treated with bismuth/clindamycin. Successful eradication of H. pylori may require combination of multiple antibiotics, as recommended at the IXth World Congress of Gastroenterology, or pharmacokinetic modulators such as H2-blockers or omeprazole.

Topics: Bismuth; Clindamycin; Double-Blind Method; Drug Therapy, Combination; Dyspepsia; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Pain Measurement; Salicylates

To determine the effect of treating Helicobacter pylori infection on the recurrence of gastric and duodenal ulcer disease.. Follow-up of up to 2 years in patients with healed ulcers who had participated in randomized, controlled trials.. A Veterans Affairs hospital.. A total of 109 patients infected with H. pylori who had a recently healed duodenal (83 patients) or gastric ulcer (26 patients) as confirmed by endoscopy.. Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet) and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given.. Endoscopy to assess ulcer recurrence was done at 3-month intervals or when a patient developed symptoms, for a maximum of 2 years.. The probability of recurrence for patients who received triple therapy plus ranitidine was significantly lower than that for patients who received ranitidine alone: for patients with duodenal ulcer, 12% (95% CI, 1% to 24%) compared with 95% (CI, 84% to 100%); for patients with gastric ulcer, 13% (CI, 4% to 31%) compared with 74% (44% to 100%). Fifty percent of patients who received ranitidine alone for healing of duodenal or gastric ulcer had a relapse within 12 weeks of healing. Ulcer recurrence in the triple therapy group was related to the failure to eradicate H. pylori and to the use of nonsteroidal anti-inflammatory drugs.. Eradication of H. pylori infection markedly changes the natural history of peptic ulcer in patients with duodenal or gastric ulcer. Most peptic ulcers associated with H. pylori infection are curable.

Topics: Adult; Aged; Aged, 80 and over; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Ranitidine; Recurrence; Risk Factors; Salicylates; Stomach Ulcer; Tetracycline

The efficacy of omeprazole in the elimination of Helicobacter pylori was investigated in a prospective randomized-controlled trial. 50 patients with upper gastrointestinal symptoms and chronic active H. pylori-associated gastritis were allocated to one of the following four therapeutic schedules: 1) omeprazole 40 mg/d for 4 weeks (n = 13); 2) bismuth subsalicylate (BSS) 3 x 600 mg for 4 weeks (n = 12); 3) omeprazole plus BSS for 4 weeks (n = 13); 4) triple therapy (BSS for 4 weeks, amoxicillin 3 x 750 mg and metronidazole 3 x 400 mg for 10 days) (n = 12). Clinical symptoms, endoscopic and histologic findings, and H. pylori status were reassessed immediately after therapy, and 1 and 6 months later. After cessation of therapy bacterial clearance rates were: 1) omeprazole 2/13 (15%); 2) BSS 6/12 (50%); 3) omeprazole plus BSS 5/13 (38%); 4) triple therapy 10/12 (83%). The degree of density of gastric mucosal infestation with H. pylori and the degree of activity of gastritis was reduced in all treatment groups but was most prominent after triple therapy. Clinical symptoms improved in all treatment groups. One and six months after completion of therapy H. pylori eradication rates were: 1) omeprazole 0/13 (0%); 2) BSS 1/12 (8%); 3) omeprazole plus BSS 1/13 (8%); 4) triple therapy 10/12 (83%). Our study shows that 40 mg/d omeprazole is ineffective in eradicating H. pylori. Dual therapy with omeprazole and bismuth subsalicylate does not improve bacterial elimination. Only triple therapy effectively eradicates H. pylori.

Topics: Adult; Aged; Amoxicillin; Bismuth; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Prospective Studies; Salicylates

To determine whether antimicrobial therapy for Helicobacter pylori infection accelerates the healing of duodenal ulcers.. Single-blind, randomized, controlled trial.. Veterans Affairs hospital.. One hundred and five patients with endoscopically verified duodenal ulcers.. Patients received either ranitidine, 300 mg/d, or ranitidine, 300 mg/d, plus "triple therapy" (2 g/d of tetracycline, 750 mg/d of metronidazole, and 5 or 8 bismuth subsalicylate tablets per day). Triple therapy was administered for only the first 2 weeks of ulcer treatment.. Videoendoscopic assessment of ulcer status was done until ulcer healing was complete. Evaluations were done after 2, 4, 8, 12, and 16 weeks of therapy.. Ulcer healing was more rapid in patients receiving ranitidine plus triple therapy than in patients receiving ranitidine alone (P less than 0.01). The cumulative percentages of patients with healed ulcers in the group receiving ranitidine plus triple therapy and in the group receiving ranitidine alone were as follows: 37% and 18% after week 2; 74% and 53% after week 4; 84% and 68% after week 8; 96% and 80% after week 12; and 98% and 84% after week 16.. Combined therapy with anti-H. pylori agents and ranitidine was superior to ranitidine alone for duodenal ulcer healing. Our results indicate that H. pylori plays a role in duodenal ulcer disease.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Ranitidine; Salicylates; Single-Blind Method; Tetracycline

Twelve healthy male subjects were dosed with six regimens: ranitidine and De-Noltab (tripotassium dicitrato bismuthate; Gist-Brocades Ltd., Weybridge, England), placebo and De-Noltab, ranitidine and Pepto-Bismol liquid [bismuth salicylate; Procter & Gamble (Health and Beauty Care) Ltd., Egham, England], placebo and Pepto-Bismol, ranitidine and Roter tablets (bismuth subnitrate; Roter Pharma Ltd., Ashford, England), and placebo and Roter. Ranitidine, 300 mg, or placebo was administered at 10 PM (night before) and at 7 AM; at 9 AM, the oral dose of bismuth was either 2 De-Noltabs, 3 30-mL doses of Pepto-Bismol liquid, or 2 Roter tablets. When predosed with placebo, the median integrated 8-hour plasma bismuth concentration was significantly greater after dosing with De-Noltabs than after dosing with either Pepto-Bismol or Roter (61, 8, and 8 ng.h/mL, respectively), with a similar trend for 8-hour median urinary bismuth excretion (213, 40, and 6 micrograms, respectively). When predosed with ranitidine, only after De-Noltab administration were there significant increases in the 8-hour plasma bismuth concentration (147 ng.h/mL), and 8-hour urinary bismuth excretion (686 micrograms). Eliminating intragastric acidity may enhance bismuth absorption after oral dosing with De-Noltabs by maintaining intragastric tripotassium dicitrato bismuthate as a colloidal suspension.

Topics: Adult; Anti-Ulcer Agents; Bismuth; Double-Blind Method; Humans; Intestinal Absorption; Male; Organometallic Compounds; Placebos; Ranitidine; Receptors, Histamine H2; Salicylates

Bismuth subsalicylate (BSS) and placebo were evaluated in a double-blind, placebo-controlled study as adjunct to rehydration therapy in 123 children, aged 4 to 28 months, hospitalized with acute diarrhea. The dosing regimen was 20 mg/kg five times daily for 5 days. Significant benefits were noted in the BSS group compared with placebo as manifested by decreases in stool frequency and stool weights and an improvement in stool consistency, significant improvement in clinical well-being, and shortening of the disease duration. Patients treated with BSS had a significant reduction in duration of hospital stay (6.9 days) compared with placebo-treated patients (8.5 days). Also, intravenous fluid requirements decreased significantly more rapidly and to a greater degree in the BSS-treated group. Bismuth subsalicylate was associated with clearance of pathogenic Escherichia coli from the stools in 100% of cases but was not different from placebo in rotavirus elimination. Bismuth subsalicylate was well tolerated with no reported adverse effects. Blood bismuth and serum salicylate levels were well below levels considered toxic. In this study, BSS provided effective adjunctive therapy for acute diarrhea, allowing children to get well sooner with less demand on the nursing and hospital staff.

Topics: Acute Disease; Bismuth; Child, Preschool; Diarrhea, Infantile; Double-Blind Method; Escherichia coli Infections; Feces; Fluid Therapy; Humans; Infant; Length of Stay; Organometallic Compounds; Rotavirus Infections; Salicylates

We assessed the relative roles of alcohol and infection with Helicobacter pylori in the pathogenesis of chronic gastritis in alcoholic patients. Helicobacter pylori was found in 14 of 18 alcoholics with dyspepsia and was associated with chronic antral gastritis. Gastric biopsy specimens were normal in four H pylori-negative alcoholics. Studies were repeated 3 to 4 weeks after controlled abstinence. There was no change in histologic findings during this period, indicating that alcohol itself was not the major causative agent. We then eliminated H pylori in 10 subjects by giving triple therapy (bismuth subsalicylate, amoxicillin, and metronidazole). Treatment for H pylori was associated with almost complete normalization of histologic findings. Four control subjects who received antacids alone showed no improvement. Dyspeptic symptoms in H pylori-positive patients significantly improved after elimination of this organism, whereas there was no change with antacid treatment.

Topics: Adult; Alcoholism; Aluminum Hydroxide; Amoxicillin; Bismuth; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Organometallic Compounds; Salicylates; Temperance

An open-label, parallel comparison of loperamide hydrochloride (Imodium A-D) and bismuth subsalicylate (Pepto-Bismol) was conducted using nonprescription dosages in adult students with acute diarrhea (three or more unformed stools in the preceding 24 hours plus at least one additional symptom of enteric infection). For the two-day study period, the daily dosage was limited to 8 mg (40 ml) for loperamide-treated subjects and to 4.9 g for bismuth subsalicylate-treated subjects. At these dosages, loperamide significantly reduced the average number of unformed bowel movements relative to bismuth subsalicylate. Following the initial dose of treatment, control of diarrhea was maintained significantly longer with loperamide than with bismuth subsalicylate. Time to last unformed stool was significantly shorter with loperamide than with bismuth subsalicylate. In providing overall subjective relief, subjects rated loperamide significantly better than bismuth subsalicylate at the end of the 24 hours. Both treatments were well tolerated, and none of the minor adverse effects reported resulted in discontinuation of therapy. It was concluded that loperamide is effective at a daily dosage limit of 8 mg (40 ml) for the treatment of acute nonspecific diarrhea and provides faster, more effective relief than bismuth subsalicylate.

Topics: Acute Disease; Adult; Bismuth; Clinical Trials as Topic; Diarrhea; Dose-Response Relationship, Drug; Female; Humans; Loperamide; Male; Nonprescription Drugs; Organometallic Compounds; Piperidines; Salicylates

The prevalence of Campylobacter pylori in gastric mucosa was investigated prospectively (by histology, cytology, bacterial culture and urease rapid-test) in 302 patients of a routine gastroenterological endoscopy programme. According to the histopathological findings the following prevalence of C. pylori was established: 3 of 35 normals (9%); 116 of 167 with antral gastritis (69%), 28 of 40 with gastric ulcers (70%); 26 of 33 with duodenal ulcers (79%); 5 of 27 with other conditions (19%). The activity degree of the gastritis correlated closely with the presence of C. pylori. In a prospective open trial 110 patients with antral gastritis or gastroduodenal ulcer were treated according to the following schedule: (a) bismuth subsalicylate, 1800 mg/d for four weeks (35 patients); (b) amoxycillin 2250 mg/d for two weeks (6); (c) ranitidine 300 mg/d for four weeks (26); (d) bismuth plus amoxycillin (20); (e) bismuth plus ranitidine (23). Immediately after the end of treatment and four weeks later the elimination rates were: (a) bismuth 51% (18) and 23% (8), respectively; (b) amoxycillin 50% (3) and 17% (1); (c) ranitidine 0% (0); (d) bismuth plus amoxycillin 60% (12) and 25% (5); (e) bismuth plus ranitidine 43% (10) and 17% (4). These data indicate that treatment with bismuth plus amoxycillin will achieve a negative bacterial result in about half the patients. But frequently as early as four weeks later C. pylori can again be demonstrated, so that the long-term elimination rate is only 15-30%.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin; Biopsy; Bismuth; Campylobacter; Campylobacter Infections; Drug Evaluation; Drug Therapy, Combination; Duodenum; Female; Gastrointestinal Diseases; Gastroscopy; Germany, West; Humans; Male; Middle Aged; Organometallic Compounds; Prospective Studies; Ranitidine; Salicylates; Stomach

Bismuth salts are successfully used for the treatment of campylobacter-pylori-associated gastritis. It cannot be excluded, however, that calcium carbonate, which is present in one of the recommended preparations (calcium carbonate/bismuth subsalicylate, Jatrox), may have an additional therapeutic effect due to an increase of intragastric pH. Therefore, the in-vitro H+ buffering capacity of Jatrox was determined in comparison to other antacids using the pH-stat technique, and its effect on intragastric acidity was tested in 15 healthy volunteers using ambulatory 24-hour pH-metry (combined glass electrode in gastric corpus, solid state memory recorder, sampling rate 30/min). At two study sessions, the volunteers received standardized normal meals (8:00 a.m., 12:00 noon, 6:00 p.m.) and, in randomized order, either Jatrox (three times 2 tablets one hour before meals) or no medication. Under in-vitro conditions, the buffering capacity of Jatrox amounts to 7.82 mmol H+ per tablet (equivalent to 47 mmol H+/24 h at recommended dosage), which is relatively low. Under in-vivo conditions, gastric pH only increases significantly during the first hour after medication. This short-lasting effect, however, has no influence on the 24-hour median pH. It is concluded from these results that the calcium carbonate contained in Jatrox probably does not contribute directly towards its therapeutic effect in promoting the healing of gastritis.

Topics: Adult; Bismuth; Calcium Carbonate; Circadian Rhythm; Drug Therapy, Combination; Female; Gastric Acidity Determination; Humans; Male; Organometallic Compounds; Salicylates

In order to assess whether bismuth subsalicylate (BSS) clears Campylobacter pylori and whether this clearance is associated with improvement in histologic gastritis, 20 patients with antral biopsies colonized by C. pylori were randomized to treatment with 30 ml of BSS (525 mg) or placebo q.i.d. for 21 days. After both 2 and 3 wk of treatment, C. pylori was cleared in 70% (7/10) of BSS-treated patients, compared with 10% (1/10) of patients on placebo (p less than 0.05) at 2 wk and 0% (0/10) of patients on placebo at 3 wk (p less than 0.01). A significant improvement in histologic gastritis (p less than 0.05) was noted after 2 and 3 wk of treatment in the group receiving BSS. Gastritis improvement was a result of both reduced polymorphonuclear and mononuclear cell infiltration. Clearance of C. pylori was highly correlated with improvement of histologic gastritis (p less than 0.001). In addition, mucus depletion scores were significantly improved in the BSS-treated group. These data indicate that treatment with BSS provides short-term clearance of C. pylori in antral mucosa, and this clearance is associated with an improvement in histologic gastritis. These findings support the pathogenic role of C. pylori in histologic antral gastritis.

Topics: Bismuth; Campylobacter; Campylobacter Infections; Gastritis; Humans; Organometallic Compounds; Prospective Studies; Random Allocation; Salicylates

The goals of this study were threefold: to compare the etiology of travelers' diarrhea in West Africa and Mexico, to evaluate two fecal transport systems for the recovery of enteropathogens, and to verify the efficacy of liquid bismuth subsalicylate (BSS) in different locations and under different entrance criteria for disease severity. The study populations consisted of 133 European tourists in West Africa and 112 American students in Mexico who had suffered from travelers' diarrhea. In 60% and 38% of the stool samples at the two study sites, similar proportions of enteropathogens were detected. A two-vial system consisting of Enteric Plus medium and polyvinyl alcohol fixative was slightly superior for identifying enteric pathogens than was a three-vial system with buffered glycerol saline, Cary-Blair medium with campylobacter antibodies, and polyvinyl alcohol fixative. In a parallel, double-blind, randomized trial, BSS significantly shortened disease duration at both study sites.

Topics: Aeromonas; Africa, Western; Animals; Bismuth; Cryptosporidium; Diarrhea; Entamoeba histolytica; Escherichia coli; Feces; Female; Giardia; Humans; Male; Mexico; Organometallic Compounds; Salicylates; Shigella; Specimen Handling; Travel

Topics: Adult; Aged; Bismuth; Campylobacter; Campylobacter Infections; Cimetidine; Clinical Trials as Topic; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Organometallic Compounds; Random Allocation; Recurrence; Salicylates; Stomach Ulcer; Wound Healing

Topics: Anti-Infective Agents; Bismuth; Campylobacter Infections; Clinical Trials as Topic; Drug Therapy, Combination; Duodenal Ulcer; Humans; Ofloxacin; Organometallic Compounds; Oxazines; Random Allocation; Salicylates

Bismuth subsalicylate (BSS) has been used for more than 80 years to treat gastrointestinal symptoms although little clinical evidence was available until recently to substantiate its value and possible mechanisms of action. BSS 4.2 g given over 3 1/2 hours was shown to reduce the number of stools passed and favorably alter subjective symptoms in patients with traveler's diarrhea. BSS has also been shown to have beneficial effects on chronic infantile diarrhea. A small but discernible effect has been shown on selected symptoms associated with Norwalk virus-induced gastroenteritis. A liquid preparation, in a dose of 60 ml qid (4.2 g/d), was 62 percent effective in preventing traveler's diarrhea during a three-week period of risk and a tablet formulation (BSS 600 mg qid) was 76 percent effective in preventing experimentally induced enterotoxigenic Escherichia coli diarrhea in volunteers. A tablet formulation (2.1 g/d) was recently shown to be 65 percent effective in preventing traveler's diarrhea during a three-week clinical trial in Mexico. Preliminary evidence suggests that the salicylate moiety exerts antisecretory effects in patients with diarrhea and the bismuth and intestinal hydrolysis products of BSS have direct antimicrobial effects.

Topics: Adolescent; Adult; Bismuth; Child; Child, Preschool; Clinical Trials as Topic; Diarrhea; Humans; Middle Aged; Organometallic Compounds; Salicylates

Within 48 hours of arrival in Mexico, 182 US students participated in a study to compare the efficacy of two dosages of bismuth subsalicylate (262 mg per tablet) as a prophylactic agent against diarrhea. The students were randomly assigned to receive two tablets (high dose) or one tablet (low dose) of bismuth subsalicylate four times daily or a placebo four times daily during a three-week period. Among these completing the trial, diarrhea (four or more unformed stools in 24 hours or three in eight hours, plus one other symptom) occurred in seven (14%) of 51 receiving the high-dose regimen compared with 15 (24%) of 63 receiving the low-dose regimen and 23 (40%) of 58 in the placebo group. Protection rates were 65% for high-dose and 40% for low-dose bismuth subsalicylate. Diarrhea caused by enterotoxigenic Escherichia coli was found in one student receiving the high-dose regimen, in no students receiving the low-dose regimen, and in seven placebo-treated subjects. Bismuth subsalicylate was well tolerated; the most common side effects were blackening of tongues and stools. Bismuth subsalicylate use in both dosages was associated with tinnitus at a low, clinically insignificant frequency of 1.2 days per 100 days of treatment. The dosage of two tablets of bismuth subsalicylate four times daily (2.1 g/d) appears to be a safe and effective means of reducing the occurrence of travelers' diarrhea among persons at risk for periods up to three weeks.

Topics: Adult; Bismuth; Diarrhea; Humans; Mexico; Organometallic Compounds; Probability; Random Allocation; Salicylates; Tablets; Travel

In a randomized double-blind study, Swiss adults traveling to tropical countries for 12 to 28 days took a solid formulation of bismuth subsalicylate (1.05 or 2.1 g/day on a twice-daily regimen) or placebo. Efficacy was evaluated in 231 volunteers. Diarrheal incidence was reduced by 41% in persons taking the high dose (P = 0.007) and by 35% in those taking the low dose (P = 0.03) with excellent compliance. No serious adverse reactions occurred, but objectionable taste, constipation, and nausea were seen more frequently with active medication (P = 0.04). Twenty patients provided stool samples: no bacteria were detected in the 8 volunteers who were on active medication, but various bacteria were found in 5 of the 12 patients who had taken placebo (P = 0.04).

Topics: Bismuth; Diarrhea; Humans; Organometallic Compounds; Patient Compliance; Salicylates; Salmonella enteritidis; Shigella dysenteriae; Tablets; Travel

Loperamide hydrochloride was compared with bismuth subsalicylate for the treatment of acute nondysenteric travelers' diarrhea in 219 students visiting seven countries in Latin America. Subjects whose condition was not improved with therapy could elect to take trimethoprim-sulfamethoxazole. Persons receiving loperamide passed fewer unformed stools when compared with the bismuth subsalicylate group during the first four hours of therapy, from four to 24 hours, and from 24 to 48 hours after therapy was initiated. Among subjects with disease due to enterotoxigenic Escherichia coli, Shigella sp, other pathogens, and unknown agents, fewer unformed stools were passed by the loperamide-treated subjects than the bismuth subsalicylate-treated subjects for all time periods studied. No significant prolongation of disease was seen in subjects with shigellosis treated with loperamide. Eight of the loperamide-treated subjects experienced constipation compared with one in the bismuth subsalicylate-treated group; otherwise, there was no difference in minor side effects experienced between both treatment groups. We conclude that loperamide is a safe and effective alternative to bismuth subsalicylate for the treatment of nondysenteric travelers' diarrhea.

Topics: Acute Disease; Adult; Antidiarrheals; Bismuth; Diarrhea; Humans; Latin America; Loperamide; Organometallic Compounds; Piperidines; Salicylates; Travel; United States

Various available forms of therapy can decrease morbidity and mortality associated with acute diarrhea. Oral fluids represent the cornerstone of therapy of all cases. A variety of agents acting nonspecifically can decrease diarrhea and improve other worrisome symptoms associated with enteric infection. Kaopectate makes the stool more formed but has little additional effects. Bismuth subsalicylate, an antisecretory agent, reduces the number of stools passed by about 50 percent and improves other associated symptomatology. The drugs that affect motility such as loperamide and diphenoxylate are the most active of the nonspecifically acting drugs. They must be avoided in patients with significant fever and dysentery. Trimethoprim/sulfamethoxazole is now considered the drug of choice for shigellosis due to the presence of ampicillin-resistant Shigella strains in most regions of the world. Trimethoprim/sulfamethoxazole is also an effective form of therapy for enterotoxigenic Escherichia coli infection and for traveler's diarrhea without definable cause. Erythromycin, although not proved to be effective against Campylobacter, probably shortens the disease. Furazolidone, although not dramatically effective, has a spectrum of activity that includes Shigella, enterotoxigenic E. coli, Campylobacter, and Giardia lamblia. It may not be effective in severely ill (hospitalized) patients with diarrhea. The various forms of available therapy can be administered empirically, depending on symptomatology. Mildly ill patients (one to three unformed stools in 24 hours with minimal additional symptoms) probably are best treated with fluids only. Mild to moderately ill persons (three to six unformed stools in 24 hours) can be treated with a drug that acts nonspecifically, such as bismuth subsalicylate or loperamide. Those with severe diseases (six or more unformed stools with moderate to severe associated symptoms), particularly when associated with fever and the passage of bloody mucoid stools, may be given an antimicrobial agent. The antimicrobial drug given will be determined by ancillary laboratory tests (dark-field examination or examination of a wet-mount preparation for motile Campylobacter or stool culture for Shigella, Campylobacter, or Salmonella) or may be administered on an empiric basis. Traveler's diarrhea can be eliminated in selected persons by the administration of a pharmacologic agent. Liquid bismuth subsalicylate is effective in large doses, which may be impr

Topics: Acute Disease; Adult; Anti-Infective Agents; Bismuth; Campylobacter Infections; Child; Child, Preschool; Clinical Trials as Topic; Diarrhea; Diarrhea, Infantile; Drug Combinations; Dysentery, Amebic; Dysentery, Bacillary; Escherichia coli Infections; Giardiasis; Humans; Infant; Kaolin; Loperamide; Narcotics; Organometallic Compounds; Parasympatholytics; Pectins; Salicylates; Salmonella Infections; Travel

Twenty-nine infants and children, age 2-70 months with chronic diarrhea, were admitted to a double-blind, parallel clinical trial. The subjects were randomly assigned to receive either a bismuth subsalicylate liquid or a placebo liquid formulation. Treatment was given for 7 days with dosage varied according to age. Analysis of the results showed that the subjects in the bismuth subsalicylate-treated group gained significantly more weight (p less than 0.05), had significantly fewer (p less than 0.01) and firmer (p less than 0.01) stools with less water content (p less than 0.01) during the course of the study than did the placebo-treated group. Response to treatment, as graded by nursing staff, family, and physicians was moderate to excellent in 86% of the treated group while none of the placebo group received such a rating (p less than 0.01). No differences were noted between stool weights or bile acid excretion.

Topics: Bismuth; Body Weight; Child, Preschool; Chronic Disease; Clinical Trials as Topic; Defecation; Diarrhea, Infantile; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant; Male; Organometallic Compounds; Prospective Studies; Random Allocation; Salicylates

Topics: Bismuth; Clinical Trials as Topic; Diarrhea; Double-Blind Method; Enterotoxins; Escherichia coli; Escherichia coli Infections; Humans; Organometallic Compounds; Salicylates; Travel

The efficacy of bismuth subsalicylate in relieving the symptoms of indigestion was evaluated in a randomized, placebo-controlled, double-blind, cross-over study in 48 adults. Each patient was treated for six episodes of indigestion, three episodes with bismuth subsalicylate and three with placebo. Volunteers took 30 ml when the symptoms first occurred and repeated the dose every half hour, as needed, for eight doses. The volunteers rated the severity of each symptom 15 and 30 minutes after each dose. Overall relief was achieved faster and in a higher proportion of cases in bismuth subsalicylate-treated episodes than in placebo-treated episodes. Bismuth subsalicylate provided greater and faster relief than placebo for nausea, sense of fullness, heartburn, feeling of abdominal distention, and flatulence, but not for upper abdominal pain.

Topics: Adolescent; Adult; Bismuth; Clinical Trials as Topic; Digestion; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Organometallic Compounds; Salicylates

The chemoprophylaxis of travellers' diarrhoea by iodochlorhydroxyquinoline combinations, neomycin and phthalsulphathiazole, furazolidone, bismuth salicylates and streptotriad is reviewed. Streptotriad is regarded as a highly effective prophylactic against travellers' diarrhoea. Some elementary food hygiene precautions are detailed.

Topics: Adult; Bismuth; Clioquinol; Diarrhea; Drug Combinations; Drug Therapy, Combination; Furazolidone; Humans; Neomycin; Organometallic Compounds; Salicylates; Streptomycin; Sulfadiazine; Sulfamethazine; Sulfathiazoles; Travel

Enterotoxigenic Escherichia coli cause most traveler's diarrhea in Third World countries. We tested bismuth subsalicylate as prophylactic therapy and as treatment for enterotoxigenic E. coli-induced diarrhea. Thirty-two healthy hospitalized volunteers were challenged orally with enterotoxigenic E. coli, strain H10407 (serotype 078:K80:H11). Administration of 600-mg doses of bismuth subsalicylate or placebo was begun 8 h before bacterial challenge. Doses were taken at 8 h and 2 h before, and at 2 h and 4 h after, the E. coli challenge and were continued four times a day for 3 additional days. The maximum prophylactic bismuth subsalicylate dose was 9.6 g. Those experiencing diarrhea were rerandomized to receive bismuth subsalicylate or placebo, given as 300 mg every 30 min for a total of 2.4 g of bismuth subsalicylate, in eight doses. Diarrhea occurred in 9 of the 16 (56%) subjects receiving placebo and in 2 of the 15 (13%) subjects receiving bismuth subsalicylate, p less than 0.03. This study confirms the effectiveness of bismuth subsalicylate in preventing traveler's (enterotoxigenic E. coli) diarrhea, and shows that bismuth subsalicylate in other than liquid form is effective. Enterotoxigenic E. coli were recovered less frequently from those receiving bismuth subsalicylate than from those receiving placebo, suggesting that bismuth subsalicylate prevents diarrhea by reducing the number or multiplication of enterotoxigenic E. coli. In vitro studies revealed that bismuth subsalicylate and its components each were bactericidal at concentrations possibly attained during the clinical trial.

Topics: Antidiarrheals; Bismuth; Diarrhea; Double-Blind Method; Escherichia coli Infections; Feces; Female; Humans; Male; Organometallic Compounds; Random Allocation; Salicylates; Travel

The influence of a typical 60-mL dose of subsalicylate bismuth (Pepto-Bismol) on the absorption of 200 mg of orally administered doxycycline hyclate was studied. Bioavailability of doxycycline was significantly reduced by 37% and 51%, respectively, when subsalicylate bismuth was given simultaneously and as a multiple-dose regimen before doxycycline. Peak serum concentrations of doxycycline were significantly decreased when subsalicylate bismuth was given two hours before doxycycline but not when given two hours after doxycycline. Subsalicylate bismuth should not be taken when doxycycline is used for therapeutic purposes, and we suggest travelers should not take the agents together in an effort to prevent diarrhea.

Topics: Adult; Biological Availability; Bismuth; Clinical Trials as Topic; Double-Blind Method; Doxycycline; Drug Interactions; Humans; Male; Organometallic Compounds; Random Allocation; Salicylates; Vomiting

The efficacy of a daily dosage regimen of subsalicylate bismuth in preventing or reducing the severity of diarrhea among young healthy adults was evaluated in a double-blind, randomized, placebo-controlled trial. Diarrhea developed in 14 (23%) of 62 students receiving subsalicylate bismuth compared with 40 (61%) of 66 students taking a placebo. The protective effect of subsalicylate bismuth was apparent within a day or two of the study onset and became more obvious as the number of days at risk increased. The students treated with subsalicylate bismuth experienced fewer intestinal complaints and were less likely to pass soft or watery stools of any number. Once diarrhea occurred, enteropathogens were less commonly identified in stools of students receiving subsalicylate bismuth (33%) compared with placebo (71%). Subsalicylate bismuth was well tolerated by students during the 21-day trial.

Topics: Adult; Bismuth; Clinical Trials as Topic; Diarrhea; Escherichia coli Infections; Humans; Mexico; Organometallic Compounds; Salicylates; Travel; United States

The therapeutic efficacy of bismuth subsalicylate was examined in a randomized double-blind fashion in 59 volunteers who were inoculated with Norwalk agent. Sixty-eight percent of the volunteers demonstrated seroconversion; 57% became ill. The severity and duration of the illness in 32 volunteers in the treatment and placebo groups were compared. Significant reduction in the severity and duration of abdominal cramps (P less than 0.01) and in the median duration of GI symptoms (P less than 0.05) was noted in the treatment group. There was no difference in the number, weight, or water content of stools, or in the rate of viral excretion between the two groups. The median duration of illness was 20 hr in the treatment group and 27 hr in the placebo group (0.1 greater than P greater than 0.05).

Topics: Adolescent; Adult; Antibodies, Viral; Bismuth; Double-Blind Method; Female; Gastroenteritis; Gastrointestinal Agents; Humans; Male; Organometallic Compounds; Parvoviridae; Random Allocation; Salicylates; Virus Diseases

The location of food consumption was recorded daily for 3 wk by 130 United States summer students newly arrived in Guadalajara, Jalisco, Mexico, as part of an assessment of bismuth subsalicylate vs. placebo in the irevention of travelers' diarrhea. Eating at locations other than homes and apartments (P < 0.025), and specifically at restaurants, was associated with an increased occurrence of diarrhea. Less eating at restaurants (P < 0.005), street vendors (P < 0.005), and school cafeterias (P < 0.01) was associated with reduced occurrence of travelers' diarrhea, even among persons taking bismuth subsalicylate as a preventive measure.

Topics: Bismuth; Diarrhea; Food Contamination; Food Microbiology; Humans; Mexico; Organometallic Compounds; Placebos; Restaurants; Salicylates; Travel; United States

Topics: Acute Disease; Appendicitis; Bismuth; Humans; Salicylates; Tomography, X-Ray Computed

Structure determination of pharmaceutical compounds is invaluable for drug development but remains challenging for those that form as small crystals with defects. Bismuth subsalicylate, among the most commercially significant bismuth compounds, is an active ingredient in over-the-counter medications such as Pepto-Bismol, used to treat dyspepsia and H. pylori infections. Despite its century-long history, the structure of bismuth subsalicylate is still under debate. Here we show that advanced electron microscopy techniques, namely three-dimensional electron diffraction and scanning transmission electron microscopy, can give insight into the structure of active pharmaceutical ingredients that are difficult to characterize using conventional methods due to their small size or intricate structural features. Hierarchical clustering analysis of three-dimensional electron diffraction data from ordered crystals of bismuth subsalicylate revealed a layered structure. A detailed investigation using high-resolution scanning transmission electron microscopy showed variations in the stacking of layers, the presence of which has likely hindered structure solution by other means. Together, these modern electron crystallography techniques provide a toolbox for structure determination of active pharmaceutical ingredients and drug discovery, demonstrated by this study of bismuth subsalicylate.

Topics: Bismuth; Helicobacter Infections; Humans; Organometallic Compounds; Pharmaceutical Preparations; Salicylates

Topics: Bismuth; Humans; Organometallic Compounds; Salicylates

Colloidal bismuth therapeutics have been used for hundreds of years, yet remain mysterious. Here we report an X-ray pair distribution function (PDF) study of the solvolysis of bismuth disalicylate, a model for the metallodrug bismuth subsalicylate (Pepto-Bismol). This reveals catalysis by traces of water, followed by multistep cluster growth. The ratio of the two major species, {Bi

Topics: Bismuth; Organometallic Compounds; Salicylates

To investigate the effect of simulated weightlessness on the pharmacokinetics of orally administered moxifloxacin and the antacid Maalox or the antidiarrheal Pepto-Bismol using a tail-suspended (TS) rat model of microgravity. Fasted control and TS, jugular-vein-cannulated, male Sprague-Dawley rats received either a single 5 mg/kg intravenous dose or a single 10 mg/kg oral dose of moxifloxacin alone or with a 0.625 mL/kg oral dose of Maalox or a 1.43 mL/kg oral dose of Pepto-Bismol. Plasma concentrations of moxifloxacin were measured by HPLC. Pharmacokinetic data were analyzed using WinNonlin. Simulated weightlessness had no effect on moxifloxacin disposition after intravenous administration but significantly decreased the extent of moxifloxacin oral absorption. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. In contrast, the coadministration of moxifloxacin with Pepto-Bismol to TS rats had no significant effect on either the rate or the extent of moxifloxacin absorption. These interactions showed dose staggering when oral administrations of Pepto-Bismol and moxifloxacin were separated by 60 min in control rats but not in TS rats. Dose staggering was more apparent after the coadministration of Maalox and moxifloxacin in TS rats.

Topics: Administration, Oral; Aluminum Hydroxide; Animals; Antacids; Anti-Bacterial Agents; Antidiarrheals; Bismuth; Drug Combinations; Drug Interactions; Magnesium Hydroxide; Male; Moxifloxacin; Organometallic Compounds; Rats; Rats, Sprague-Dawley; Salicylates; Weightlessness; Weightlessness Simulation

Topics: Aged; Antidiarrheals; Bismuth; Chronic Disease; Colitis, Microscopic; Diagnosis, Differential; Diarrhea; Female; Humans; Intestinal Mucosa; Organometallic Compounds; Salicylates

Periodontitis is a chronic, multifactorial, inflammatory disease characterized by the progressive destruction of the periodontal tissues. Guided tissue regeneration (GTR), involving the use of barrier membranes, is one of the most successful clinical procedures for periodontal therapy. Nevertheless, rapid degradation of the membranes and membrane-related infections are considered two of the major reasons for GTR clinical failure. Recently, integration of non-antibiotic, antimicrobial materials to the membranes has emerged as a novel strategy to face the bacterial infection challenge, without increasing bacterial resistance. In this sense, bismuth subsalicylate (BSS) is a non-antibiotic, metal-based antimicrobial agent effective against different bacterial strains, that has been long safely used in medical treatments. Thus, the aim of the present work was to fabricate fibrillar, non-rapidly bioresorbable, antibacterial GTR membranes composed of polycaprolactone (PCL), gelatin (Gel), and BSS as the antibacterial agent. PCL-G-BSS membranes with three different BSS concentrations (2 wt./v%, 4 wt./v%, and 6 wt./v%) were developed by electrospinning and their morphology, composition, water wettability, mechanical properties, Bi release and degradation rate were characterized. The Cytotoxicity of the membranes was studied

Topics: Anti-Bacterial Agents; Biocompatible Materials; Bismuth; Cell Survival; Cells, Cultured; Electrochemical Techniques; Fibroblasts; Gelatin; Gingiva; Guided Tissue Regeneration, Periodontal; Humans; Membranes, Artificial; Organometallic Compounds; Polyesters; Salicylates

Topics: Aged, 80 and over; Anemia; Antidiarrheals; Betacoronavirus; Bismuth; Blood Sedimentation; C-Reactive Protein; Coronavirus Infections; Cough; COVID-19; Crohn Disease; Diarrhea; Humans; Lymphopenia; Male; Organometallic Compounds; Pandemics; Pneumonia, Viral; Salicylates; SARS-CoV-2; Treatment Outcome

Topics: Anti-Bacterial Agents; Antidiarrheals; Antiprotozoal Agents; Bismuth; Campylobacter Infections; Dysentery; Enteropathogenic Escherichia coli; Escherichia coli; Escherichia coli Infections; Giardiasis; Humans; Loperamide; Multiplex Polymerase Chain Reaction; Organometallic Compounds; Salicylates; Shiga-Toxigenic Escherichia coli; Travel-Related Illness

A replicated 5 × 5 Latin square design with a 2 × 2 + 1 factorial arrangement of treatments was used to determine the effects of bismuth subsalicylate (BSS) and encapsulated calcium ammonium nitrate (eCAN) on ruminal fermentation of beef cattle consuming bahiagrass hay (Paspalum notatum) and sugarcane molasses. Ten ruminally cannulated steers (n = 8; 461 ± 148 kg of body weight [BW]; average BW ± SD) and heifers (n = 2; 337 ± 74 kg of BW) were randomly assigned to one of five treatments as follows: 1) 2.7 g/kg of BW of molasses (NCTRL), 2) NCTRL + 182 mg/kg of BW of urea (U), 3) U + 58.4 mg/kg of BW of BSS (UB), 4) NCTRL + 538 mg/kg of BW of eCAN (NIT), and 5) NIT + 58.4 mg/kg of BW of BSS (NITB). With the exception of NCTRL, all treatments were isonitrogenous. Beginning on day 14 of each period, ruminal fluid was collected and rectal temperature was recorded 4× per day for 3 d to determine ruminal changes every 2 h from 0 to 22 h post-feeding. Ruminal gas cap samples were collected at 0, 3, 6, 9, and 12 h on day 0 of each period followed by 0 h on days 1, 2, 3, and 14. Microbial N flow was determined using Cr-Ethylenediaminetetraacetic acid, YbCl3, and indigestible neutral detergent fiber for liquid, small particle, and large particle phases, respectively. Data were analyzed using the MIXED procedure of SAS. Orthogonal contrasts were used to evaluate the effects of nonprotein nitrogen (NPN) inclusion, NPN source, BSS, and NPN source × BSS. There was no treatment effect (P > 0.05) on concentrations of H2S on day 0, 1, 2, or 14; however, on day 3, concentrations of H2S were reduced (P = 0.018) when NPN was provided. No effect of treatment (P = 0.864) occurred for ruminal pH. There was an effect of NPN source on total concentrations of VFA (P = 0.011), where a 6% reduction occurred when eCAN was provided. There were effects of NPN (P = 0.001) and NPN source (P = 0.009) on the concentration of NH3-N, where cattle consuming NPN had a greater concentration than those not consuming NPN, and eCAN reduced the concentration compared with urea. Total concentrations of VFA and NH3-N were not affected (P > 0.05) by BSS. There was an effect of BSS (P = 0.009) on rectal temperature, where cattle not consuming BSS had greater temperatures than those receiving BSS. No differences for NPN, NPN source, nor BSS (P > 0.05) were observed for microbial N flow. In conclusion, eCAN does not appear to deliver equivalent ruminal fermentation parameters compared with urea, and BSS

Topics: Animal Feed; Animals; Bismuth; Cattle; Diet; Dietary Supplements; Digestion; Fermentation; Male; Molasses; Nitrates; Nitrogen; Organometallic Compounds; Paspalum; Quaternary Ammonium Compounds; Rumen; Saccharum; Salicylates; Urea

Two randomized block designs were performed to evaluate the effects of bismuth subsalicylate (BSS) and encapsulated calcium-ammonium nitrate (eCAN) on enteric methane production, nutrient digestibility, liver mineral concentration, and performance of beef cattle consuming bahiagrass hay (Paspalum notatum; ad libitum) and sugar cane molasses [1.07 kg/d; dry matter basis]. Experiment 1, used 25 crossbred steers [335 ± 46 kg of initial body weight (BW)] with a 2 × 2 + 1 factorial arrangement of treatments for two 20 d periods. Factors were nonprotein nitrogen (NPN) source (350 mg/kg BW of nitrate or 182 mg/kg BW of urea), BSS (0 or 58.4 mg/kg BW), and a negative control (NCTRL; bahiagrass hay and molasses only). Steers were re-randomized for a second period (n = 10/treatment total). Intake, apparent total tract digestibility and enteric methane were evaluated. Experiment 2 used 75 crossbred heifers in 25 pens (3 heifers/pen; 279 ± 57 kg of initial BW), consuming the same diet and treatments as experiment 1, to determine liver mineral concentration and growth performance over 56 d. Orthogonal contrasts were used to evaluate the effects of NPN (NCTRL vs. others), source of NPN (NS; urea vs. eCAN), BSS, and NS × BSS. For experiment 1, no interactions were observed for any variables, nor were there any effects of NPN on total tract digestibility of nutrients, except for crude protein. Digestibility of all nutrients was reduced (P ≤ 0.021) for steers consuming eCAN compared with urea. There was no effect (P > 0.155) of BSS on digestibility of nutrients; however, BSS reduced (P = 0.003) apparent S retention. Enteric CH4 emission (g/kg BW0.75) was decreased (P = 0.051) by 11% with the addition of eCAN compared with urea. For experiment 2, no NS × BSS interactions (P ≥ 0.251) were observed to affect liver mineral concentration; however, the addition of BSS decreased liver concentration of Cu (P = 0.002) while increasing Fe concentration (P = 0.016). There was an NS × BSS interaction (P = 0.048) where heifers consuming eCAN and BSS had lesser final BW compared with heifers consuming urea and BSS. While eCAN may be a viable resource for mitigating enteric CH4 production of forage-fed cattle, the negative effects on digestibility should be considered. Furthermore, BSS, at the amount provided, appears to have no negative effects on digestibility of nutrients in forage-fed cattle; however, there may be deleterious impacts on performance depending upon what nitrogen sourc

Topics: Animal Feed; Animals; Bismuth; Cattle; Diet; Dietary Supplements; Digestion; Female; Gastrointestinal Tract; Liver; Male; Methane; Minerals; Molasses; Nitrates; Nutrients; Organometallic Compounds; Paspalum; Quaternary Ammonium Compounds; Random Allocation; Saccharum; Salicylates; Urea

A 79-year-old man presented to the emergency department with a 1-week history of worsening confusion, falls and hearing impairment. An initial workup for infectious, metabolic and structural causes was unrevealing. However, further history discovered that he had been ingesting one to two bottles of Pepto-Bismol (bismuth subsalicylate) daily for gastro-oesophageal reflux symptoms. On his second day of admission, the plasma salicylate concentration was 2.08 mmol/L (reference range 1.10-2.20 mmol/L), despite no sources of salicylate in hospital. He was diagnosed with chronic salicylate toxicity and Pepto-Bismol use was discontinued. The patient was treated supportively with isotonic intravenous fluids only and plasma salicylate concentration fell to less than 0.36 mmol/L. Concurrently, all his symptoms resolved. This case highlights the potential adverse effects of over-the-counter medications. The diagnosis of chronic salicylate toxicity is challenging, specifically in the elderly and in undifferentiated presentations, as it can be missed if not suspected.

Topics: Accidental Falls; Aged; Bismuth; Confusion; Diagnosis, Differential; Hearing Disorders; Humans; Male; Organometallic Compounds; Salicylates

Drugs containing bismuth, although usually safe, may rarely cause neurotoxicity.. We describe the case of a 44-year-old woman treated with bismuth subsalicylate for about 20 years, who developed abnormal behaviour and postural instability in two weeks. On examination, she had greyish discoloration of teeth, was confused and presented generalized myoclonic jerks. In the next days, her clinical condition deteriorated, with a reduction in alertness and more exuberant myoclonus. Brain MRI was unremarkable. CSF revealed mild elevation of protein content (47 mg/dL; reference range: 15-45 mg/dL) and elevation of white blood cell count (10/μL). Bismuth levels in urine (375 μg/L), serum (260 μg/L) and CSF (21.4 μg/L) samples were highly above the threshold for toxicity. Following supportive treatment and bismuth discontinuation, she made a full recovery within weeks.. Although rare, bismuth encephalopathy should be considered in patients presenting with subacute encephalopathy and myoclonus. This encephalopathy can be subacute even after a chronic exposure. Cessation of bismuth can lead to a complete resolution in weeks.

Topics: Adult; Bismuth; Brain Diseases; Female; Humans; Neurotoxicity Syndromes; Organometallic Compounds; Salicylates

The study of pharmacological interactions between herbal remedies and conventional drugs is important because consuming traditional herbal remedies as supplements or alternative medicine is fairly common and their concomitant administration with prescribed drugs could either have a favorable or unfavorable effect. Therefore, this work aims to determine the pharmacological interactions of a turmeric acetone extract (TAE) and its main metabolite (curcumin) with common anti-ulcer drugs (ranitidine and bismuth subsalicylate), using an ethanol-induced ulcer model in Wistar rats. The analysis of the interactions was carried out via the Combination Index-Isobologram Equation method. The combination index (CI) calculated at 0.5 of the affected fraction (fa) indicated that the TAE or curcumin in combination with ranitidine had a subadditive interaction. The results suggest that this antagonistic mechanism is associated to the mucoadhesion of curcumin and the TAE, determined by rheological measurements. Contrastingly, both the TAE and curcumin combined with bismuth subsalicylate had an additive relationship, which means that there is no pharmacological interaction. This agrees with the normalized isobolograms obtained for each combination. The results of this study suggest that mucoadhesion of curcumin and the TAE could interfere in the effectiveness of ranitidine, and even other drugs.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Curcuma; Curcumin; Disease Models, Animal; Drug Interactions; Ethanol; Gastric Mucosa; Herb-Drug Interactions; Male; Organometallic Compounds; Plant Extracts; Ranitidine; Rats; Rats, Wistar; Salicylates; Stomach Ulcer

Bismuth subsalicylate (BSS) is the active ingredient in over-the-counter antacid and antidiarrheal medications. Coagulopathy in the setting of acetylsalicylic acid toxicity is well documented but not in setting of bismuth subsalicylate overuse. We present a case report of coagulopathy from BSS poisoning in a patient with underlying cirrhosis. The patient's high prothrombin time suggests inhibition of vitamin K-dependent coagulation factors. The patient had decreased factor V activity, which is responsible for converting prothrombin to thrombin. Patients with cirrhosis often have hypoprothrombinemia which may be exacerbated by salicylate-induced coagulopathy. Given the widespread use of BSS products, physicians should recognize coagulopathy as a possible manifestation of toxicity especially in patients with underlying liver disease.

Topics: Bismuth; Blood Coagulation Disorders; Chronic Disease; Female; Humans; International Normalized Ratio; Liver Cirrhosis; Middle Aged; Organometallic Compounds; Salicylates

Topics: Adult; Aged; Aged, 80 and over; Antidiarrheals; Biopsy; Bismuth; Colitis, Lymphocytic; Collagen; Female; Humans; Male; Mesalamine; Middle Aged; Organometallic Compounds; Salicylates; Steroids; Treatment Outcome

Topics: Amoxicillin; Anti-Bacterial Agents; Bismuth; Clarithromycin; Doxycycline; Female; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Lymphoma, B-Cell; Metronidazole; Middle Aged; Organometallic Compounds; Rabeprazole; Salicylates

Topics: Anniversaries and Special Events; Antacids; Anti-Bacterial Agents; Asthma; Bacterial Vaccines; Bismuth; Drug Resistance, Bacterial; Drug Therapy, Combination; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Nobel Prize; Organometallic Compounds; Peptic Ulcer; Probiotics; Salicylates; Stress, Psychological

Topics: Adolescent; Bezoars; Biomarkers; Bismuth; Female; Humans; Organometallic Compounds; Radiography; Salicylates; Stomach; Suicide, Attempted

In recent years, nanomaterials have been used in the medical-dental field as new alternative antimicrobial agents. Bismuth subsalicylate (BSS) has been used as an antimicrobial agent, but the effect of BSS in the form of nanoparticles (BSS-nano) as a potential antimicrobial agent has not been tested, in specific against bacteria responsible for periodontal disease. The aim of this study was to evaluate the antibacterial effect of BSS-nano against oral anaerobic bacteria and to assess the safety of BSS-nano by evaluating their cytotoxicity in human gingival fibroblast (HGF-1) cells. BSS-nano were synthesized by laser ablation and were previously physico-chemically characterized using in vitro assays. The antibacterial activity was measured using the tetrazolium-based XTT assay, and cytotoxicity was determined using lactate dehydrogenase (LDH) and MTS assays in HGF-1 cells. Transmission electron microscopy of HGF-1 exposed to BSS-nano was also performed. BSS-nano was shown to have a primary size of 4-22 nm and a polygonal shape. Among the tested bacterial strains, those with a greater sensitivity to BSS-nano (highest concentration of 21.7 μg ml

Topics: Aggregatibacter actinomycetemcomitans; Anaerobiosis; Anti-Bacterial Agents; Bismuth; Cell Line; Cell Survival; Drug Compounding; Fibroblasts; Gingiva; Humans; L-Lactate Dehydrogenase; Microbial Sensitivity Tests; Nanoparticles; Organometallic Compounds; Porphyromonas gingivalis; Salicylates

Hydrogen sulfide (H. Eighty mice were randomized to five groups consisting of Live SRB, Killed SRB, SRB+Bismuth, Bismuth, and Saline. Desulfovibrio vulgaris, a common strain of SRB, was administered by gavage at the dose of 1.0 × 10. The Live SRB group had slower intestinal transit as represented by a geometric center score of 40.2 ± 5.7 when compared to Saline: 73.6 ± 5.7, Killed SRB: 77.9 ± 6.9, SRB+Bismuth: 81.0 ± 2.0, and Bismuth: 73.3 ± 4.2 (P<.0001). Correspondingly, the Live SRB group had the highest luminal H. Live SRB slow intestinal transit in a bismuth-reversible fashion in mice. Our results demonstrate that intestinal transit is slowed by SRB and this effect could be abolished by H

Topics: Animals; Bismuth; Desulfovibrio vulgaris; Female; Gastrointestinal Transit; Hydrogen Sulfide; Intestine, Small; Mice; Mice, Inbred C57BL; Organometallic Compounds; Random Allocation; Salicylates

Aim. There is a paucity of data on the efficacy of empiric H. pylori treatment after multiple treatment failures. The aim of this study is to examine the efficacy of empiric salvage therapy as a second through sixth line treatment. Methods. In this single gastroenterology center prospective study in Montreal, Canada, patients with failed H. pylori treatment were offered empiric salvage therapy based on the patients' previous antibiotic exposure. Enrollment occurred after 1-5 previous failed attempts and eradication determined at least 4 weeks after completion of treatment. Results. 205 treatments were attempted in 175 patients using 7 different regimens. Eradication was achieved in 154 attempts (PP = 81% (154/191), ITT = 75% (154/205)). Bismuth quadruple therapy (BQT) had higher eradication success (PP = 91% (102/112), ITT = 84% (102/121)) when compared to all PPI triple therapies combined (PP = 66% (49/74), absolute risk reduction (ARR): 25% (95% CI: 13-37), ITT = 62% (49/79), ARR: 22% (95% CI: 10-35), and p < 0.001) and when compared to levofloxacin triple therapy (PP = 66% (40/61), ARR: 26% (95% CI: 13-39), ITT = 61% (40/66), and ARR: 24% (95% CI: 10-37)). Eradication was achieved in a high proportion with BQT on attempt two (PP = 94% (67/71), ITT = 91% (67/74)), three (PP = 85% (17/20), ITT = 71% (17/24)), four (PP = 100% (11/11), ITT = 92% (11/12)), and five (PP = 86% (6/7), ITT = 75% (6/8)). Patients with previous combined bismuth and tetracycline exposure had a lower proportion of eradication compared to patients without such an exposure (PP: 60% (6/10) versus 95% (94/99), ARR: 35% (95% CI: 11-64), and p < 0.001; ITT: 55% (6/11) versus 90% (94/105), ARR: 35% (95% CI: 10-62), and p < 0.01). Conclusions. Salvage therapy with a bismuth quadruple regimen is superior to triple therapies and is effective for second through fifth line empirical treatment (≥85% PP, ≥70% ITT). Successful eradication is significantly lower with BQT if a similar bismuth based regimen was used in the past.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bismuth; Canada; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Intention to Treat Analysis; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Organometallic Compounds; Prospective Studies; Proton Pump Inhibitors; Salicylates; Salvage Therapy; Tetracycline; Treatment Failure; Treatment Outcome; Young Adult

Renal pigmentation due to the administration of exogenous compounds is an uncommon finding in most species. This report describes renal pigmentation and intranuclear inclusions of the proximal convoluted tubules due to chronic bismuth administration in a rhesus macaque. An 11-year-old Indian-origin rhesus macaque with a medical history of chronic intermittent vomiting had been treated with bismuth subsalicylate, famotidine, and omeprazole singly or in combination over the course of 8 years. At necropsy, the renal cortices were diffusely dark green to black. Light and electron microscopy revealed intranuclear inclusions within the majority of renal proximal tubular epithelial cells. These inclusions appeared magenta to brown when stained with hematoxylin and eosin and were negative by the Ziehl-Neelsen acid-fast stain. Elemental analysis performed on frozen kidney measured bismuth levels to be markedly elevated at 110.6 ppm, approximately 500 to 1000 times acceptable limits. To our knowledge, this is the first report of renal bismuth deposition in a rhesus macaque resulting in renal pigmentation and intranuclear inclusions.

Topics: Animals; Antiemetics; Bismuth; Kidney; Kidney Diseases; Macaca mulatta; Male; Monkey Diseases; Organometallic Compounds; Pigmentation; Pigmentation Disorders; Salicylates; Vomiting

Topics: Animals; Bismuth; Dog Diseases; Dogs; Foreign Bodies; Intestinal Obstruction; Male; Organometallic Compounds; Salicylates; Tablets; Textiles

Previous studies have shown bismuth subsalicylate (BSS) has antimicrobial properties, but few studies have addressed the mechanism of action. Furthermore, following BSS ingestion other bismuth salts form throughout the gastrointestinal tract including bismuth oxychloride (BiOCl) that also act upon enteric pathogens. To further understand the antimicrobial activity of bismuth in infectious diarrhea, the antimicrobial effect of BSS and BiOCl on Clostridium difficile, Salmonella, Shigella, Shiga toxin-producing Escherichia coli strains and norovirus (NoV) were measured. Bacterial enteric pathogens in pure culture or in human fecal material were exposed to 35mg/ml BSS or BiOCl with or without a vehicle suspension. BSS and BiOCl treated samples were quantified and visualized by transmission electron microscopy. To measure the effect on NoV, reduction of infectious murine NoV (MNV), a surrogate for human NoV, and Norwalk virus RNA levels were measured by viral plaque assay and RT-qPCR, respectively. BSS and BiOCl reduced bacterial growth by 3-9 logs in all strains with majority resulting in populations of <10 cfu/ml within 24 h. Similar results were found when fecal material was included. Microscopy images detected bismuth on bacterial membranes and within the bacterial organisms at 30 min post-treatment. At 8.8mg/ml BSS and BiOCl reduced infectivity of MNV significantly by 2.7 and 2.0 log after 24 h of exposure. In addition, both BSS and BiOCl slightly reduced the level of Norwalk replicon-bearing cells suggesting that bismuth may inhibit NoV in vivo. Collectively, our results confirm and build on existing data that BSS has antimicrobial properties against a wide-range of diarrhea-causing pathogens.

Topics: Animals; Anti-Infective Agents; Bacterial Load; Bismuth; Clostridioides difficile; Enterobacteriaceae; Humans; Mice; Microbial Sensitivity Tests; Microbial Viability; Microscopy, Electron, Transmission; Norovirus; Organometallic Compounds; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Salicylates; Viral Load; Viral Plaque Assay

Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory disorders of the colon. There is a paucity of data on differences in etiology, natural history, and treatment response between CC and LC.. Between 2002 and 2013, we identified new diagnoses of CC and LC using the Research Patient Data Registry in a tertiary referral center. We used chi square or Fischer's exact test and Wilcoxon rank-sum tests to compare the differences in clinical characteristics, treatment types, and response rates between LC and CC.. Through 2013, we confirmed 131 patients with a new diagnosis of microscopic colitis (MC) (55 LC, 76 CC). Compared to cases of LC, patients with a diagnosis of CC were more likely to be women (86% vs. 69%, p = 0.03), have elevated erythrocyte sedimentation rate (mean 28 vs. 13 mm/h, p = 0.04), and less likely to be diabetic (5% vs. 18%, p = 0.02). Budesonide was the most effective treatment for both CC and LC (94% and 80%, respectively). However, there were no statistically significant differences in response to various treatments according to the type of MC (all p > 0.10). Older age at the time of diagnosis was associated with better response to bismuth subsalicylate (odds ratio: 1.76; 95% confidence interval: 1.21-2.56 for every 5-year increase) for both CC and LC.. Despite differences in the clinical characteristics, response rates to available treatments appeared to be similar in both LC and CC. Older patients may have a better response to bismuth subsalicylate therapy.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Bismuth; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Female; Humans; Logistic Models; Male; Middle Aged; Organometallic Compounds; Salicylates; Tertiary Care Centers; Treatment Outcome

The prevalence of metronidazole-resistant H. pylori is almost 50% in Thailand which severely limits the use of this drug for eradication therapy. The aims of this study were to evaluate the efficacy and safety profiles of 7-day bismuth-based quadruple therapy including metronidazole as an initial treatment for H. pylori infection in a high metronidazole resistance area.. This study was performed at Thammasat University Hospital and King Chulalongkorn Memorial Hospital during January 2009 to October 2010. Patients with non-ulcer dyspepsia (NUD) with active H. pylori infection were assigned to receive seven days of quadruple therapy (pantoprazole 40 mg bid, bismuth subsalicylate 1,048 mg bid, amoxicillin 1 gm bid and metronidazole 400 mg tid). H. pylori infection was defined as positive H. pylori culture or two positive tests (rapid urease test and histology). Antibiotic susceptibility test for metronidazole by Epsilometer test (E-test) was performed in all positive cultures. At least four weeks after treatment, 13C urea breath test (13C-UBT) was performed to confirm H. pylori eradication.. A total of 114 patients were enrolled in this study, 50 males and 64 females with a mean age of 49.8 years. All 114 patients had a diagnosis of NUD. Overall eradication as confirmed by negative 13C-UBT was achieved in 94 out of 114 patients (82.5%). 44 patients had positive cultures and success for E-test. In vitro metronidazole resistance was observed in 22/44 (50%) patients. Eradication rate in patients with metronidazole resistant strains was 16/22 (72.7%) and 20/22 (90.1%) with metronidazole sensitive strains (72.7% vs 90.1%, p-value=0.12; OR=3.75 [95%CI=0.6-31.5]). Minor adverse reactions included nausea, bitter taste, diarrhea and black stools but none of the patients dropped out from the study.. Initial treatment with 7-day bismuth-based quadruple therapy including metronidazole, amoxycillin and pantoprazole is highly effective and well tolerated for metronidazole-sensitive H. pylori infections. However, the efficacy markedly decline with metronidazole resistance. Longer duration of this regimen might be required to improve the eradication rate and larger multi-center studies are needed to confirm this hypothesis.

Topics: Anti-Bacterial Agents; Bismuth; Breath Tests; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Prognosis; Salicylates; Thailand

The objective of this study was to determine if a sulfur binder, bismuth subsalicylate (BSS), alone or combined with monensin (MON) could decrease the production of HS by rumen microbes. In Exp. 1, two 24-h batch culture incubations were conducted using a substrate consisting of 50% corn, 40% distillers grains, 9.75% hay, and 0.25% mineral premix, on a DM basis. Five treatments including BSS concentrations of 0% (control), 0.5%, 1%, 2%, and 4% of DM were assigned in 5 replicates to 120-mL serum bottles containing rumen fluid, buffer, and 0.5 g of dietary substrate. Addition of 2% and 4% BSS decreased ( < 0.05) gas production, whereas all concentrations of BSS reduced ( < 0.05) HS production by 18%, 24%, 82%, and 99% for 0.5%, 1%, 2%, and 4% BSS, respectively. Final pH increased ( < 0.05) with 2% and 4% BSS treatments. At 4% of DM, BSS decreased ( < 0.05) total VFA concentration (m) and propionate (mol/100 mol) but increased acetate (mol/100 mol) and acetate to propionate ratio. Concentration of branched-chain VFA increased ( < 0.05) with the addition of 0.5% BSS, compared with the control. On the basis of these results, addition of BSS (1% of DM) and MON (5 mg/kg) were used to assess their effects on metabolism and HS release by rumen microbes in 8 dual flow continuous culture fermenters during two 10-d periods (Exp. 2). Treatments were arranged in a 2 × 2 factorial design. Substrate similar to that used in Exp. 1 was provided at 75 g DM/fermenter daily. Headspace HS concentration was reduced ( < 0.05) by 99% with BSS treatment but was not affected ( = 0.21) by MON. An overall increase ( < 0.05) in fermentation pH was found following addition of BSS. Addition of BSS increased ( < 0.05) digestion of NDF and ADF but decreased ( < 0.05) nonfiber carbohydrate digestion and total VFA concentration. Acetate and propionate (mol/100 mol) increased ( < 0.05) with BSS, whereas butyrate (mol/100 mol) and branched-chain VFA (m) decreased ( < 0.05). Addition of BSS increased ( < 0.05) NH-N concentration and NH-N outflow but decreased ( < 0.05) microbial N outflow. Results from this study showed no response to monensin addition, but BSS markedly reduced HS production and altered microbial fermentation during in vitro rumen fluid incubations.

Topics: Animal Feed; Animals; Bismuth; Cattle; Diet; Digestion; Fermentation; Hydrogen; Hydrogen Sulfide; Monensin; Organometallic Compounds; Rumen; Salicylates

We determined the in vitro susceptibility of clinical isolates of Helicobacter pylori to ZnCl, compared its sensitivity to bismuth subsalicylate (BSS) and clarithromycin (CLR) that are used for the treatment of H. pylori infection and its activity at different gastric pH. One hundred sixteen clinical isolates of H. pylori strains were chosen. Agar gel dilution method was used to determine the susceptibility of H. pylori isolates to ZnCl 40 μg/ml, BSS 20 μg/ml, and CLR 2 μg/ml. Suspension of 10(9) bacteria/μl was streaked on the blood agar plate. The control consisted of H. pylori incubated without ZnCl, BSS, and CLR. One hundred ten H. pylori strains (95%) were susceptible to ZnCl 40 μg/ml compared to 114 (98%) to BSS 20 μg/ml (p=0.002) and 92 (79%) to CLR 2 μg/ml (p=0.602). H. pylori isolates from patients with nonulcer dyspepsia and from peptic ulcer were equally susceptible to ZnCl 40 μg/ml (90/96 vs. 26/26, p=0.208). H. pylori associated with chronic gastritis and chronic active gastritis were equally susceptible to ZnCl. H. pylori demonstrated susceptibility to ZnCl in vitro. H. pylori susceptibility to ZnCl 40 μg/ml was greater than BSS and comparable to CLR. ZnCl may be used in the treatment of H. pylori infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Bismuth; Chlorides; Chronic Disease; Clarithromycin; Drug Resistance, Bacterial; Dyspepsia; Female; Gastric Juice; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Microbial Sensitivity Tests; Middle Aged; Organometallic Compounds; Peptic Ulcer; Salicylates; Zinc Compounds

Adipose tissue hormone leptin induces endothelium-dependent vasorelaxation mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factors (EDHF). Previously it has been demonstrated that in short-term obesity the NO-dependent and the EDHF-dependent components of vascular effect of leptin are impaired and up-regulated, respectively. Herein we examined the mechanism of the EDHF-dependent vasodilatory effect of leptin and tested the hypothesis that alterations of acute vascular effects of leptin in obesity are accounted for by chronic hyperleptinemia. The study was performed in 5 groups of rats: (1) control, (2) treated with exogenous leptin for 1 week to induce hyperleptinemia, (3) obese, fed highly-palatable diet for 4 weeks, (4) obese treated with pegylated superactive rat leptin receptor antagonist (PEG-SRLA) for 1 week, (5) fed standard chow and treated with PEG-SRLA. Acute effect of leptin on isometric tension of mesenteric artery segments was measured ex vivo. Leptin relaxed phenylephrine-preconstricted vascular segments in NO- and EDHF-dependent manner. The NO-dependent component was impaired and the EDHF-dependent component was increased in the leptin-treated and obese groups and in the latter group both these effects were abolished by PEG-SRLA. The EDHF-dependent vasodilatory effect of leptin was blocked by either the inhibitor of cystathionine γ-lyase, propargylglycine, or a hydrogen sulfide (H2S) scavenger, bismuth (III) subsalicylate. The results indicate that NO deficiency is compensated by the up-regulation of EDHF in obese rats and both effects are accounted for by chronic hyperleptinemia. The EDHF-dependent component of leptin-induced vasorelaxation is mediated, at least partially, by H2S.

Topics: Adipose Tissue; Alkynes; Animals; Biological Factors; Bismuth; Cystathionine gamma-Lyase; Diet; Endothelium, Vascular; Gene Expression Regulation; Glycine; Hydrogen Sulfide; Leptin; Male; Mesenteric Arteries; Nitric Oxide; Nitric Oxide Synthase Type III; Obesity; Organometallic Compounds; Phenylephrine; Rats; Rats, Wistar; Receptors, Leptin; Salicylates; Signal Transduction; Tissue Culture Techniques; Vasoconstriction; Vasodilation

Salen bismuth alkoxides, where the salen ligand contains 2,4-di-tert-butylphenoxy groups and one of ethylene, cyclohexane or ortho-phenyl as a backbone have been prepared from reactions involving Bi[N(SiMe₃)₂]₃ and the free salen ligand followed by alcoholysis (ButOH, PriOH and 2,6-But₂C₆H₃OH). The molecular structures of the salen ligand with the cyclohexyl back-bone have been determined for the complexes salenBiCl and salenBiOC₆H₃-2,6-But₂. The chloro compound is a dimer with chloride bridges while the phenoxide is monomeric with an unusually distorted five-coordinate geometry. The phenoxide and tert-butoxide complexes have been employed in the ring-opening polymerization of lactides (L- and rac-) to give polylactides, PLAs. With rac-LA heterotactic PLA is formed preferentially, Pr = ~0.9, in dichloromethane or toluene at room temperature. The reaction is first order in [Bi] and is notably faster than most aluminum and zinc initiators as well as tin(II) octanoate. These results are discussed in terms of a recent report on the polymerization of LA by Peptobismol® and bismuth subsalicylate.

Topics: Bismuth; Catalysis; Coordination Complexes; Crystallography, X-Ray; Dioxanes; Ethylenediamines; Kinetics; Molecular Conformation; Organometallic Compounds; Polyesters; Salicylates

Recently, I had a visit from a 5-year-old patient who had been given bismuth subsalicylate for a diarrheal illness by a local family physician during a trip to South America. Is this a practice we should encourage?. Research from developing countries has found the use of bismuth subsalicylate to be effective in shortening the duration of diarrheal illness. Despite these findings, its limited effectiveness and concerns about it potentially causing Reye syndrome, compliance, and cost are the key reasons it is not routinely recommended for children.

Topics: Antidiarrheals; Bismuth; Child; Cost-Benefit Analysis; Developing Countries; Diarrhea; Evidence-Based Medicine; Humans; Organometallic Compounds; Reye Syndrome; Salicylates

We report a case of an inadvertent increase in the international normalized ratio (INR) after the addition of bismuth subsalicylate for the treatment of diarrhea in an enterally fed patient receiving warfarin therapy. A 56-year-old Caucasian female presented to the trauma intensive care unit (ICU) with multiple lower extremity fractures. Warfarin was initiated for deep vein thrombosis prophylaxis due to the patient's inability to ambulate. The target INR was 2-3. Continuous intragastric enteral feeding was withheld 1 hour before and 1 hour after intragastric administration of warfarin. Bismuth subsalicylate 30 mL every 4 hours was prescribed for diarrhea. Within 3 days after starting bismuth subsalicylate therapy, the patient's INR increased from 2.56 to 3.54 and minor bleeding was noted from the patient's tracheostomy site. No significant change in warfarin dosage, variability in vitamin K intake, or medications that potentially alter warfarin metabolism were present during the unexpected rise in INR. When the bismuth subsalicylate was discontinued, the patient's INR stabilized into the target range on the same warfarin dose given at the time of the supratherapeutic INR. Salicylate displaces warfarin from plasma protein binding sites and may result in a significant increase in INR secondary to redistribution of warfarin to the free active form. Evaluation of this case report using the Drug Interaction Probability Scale and Naranjo Adverse Drug Reaction Probability Scale yielded scores consistent with a probable adverse drug interaction. Bismuth subsalicylate exaggerates warfarin's anticoagulant response and its concurrent use during warfarin therapy should be avoided.

Topics: Anticoagulants; Bismuth; Drug Interactions; Enteral Nutrition; Female; Humans; International Normalized Ratio; Middle Aged; Organometallic Compounds; Salicylates; Warfarin

To evaluate the feasibility of using a commercially available clinical dual-energy computed tomographic (CT) scanner to differentiate the in vivo enhancement due to two simultaneously administered contrast media with complementary x-ray attenuation ratios.. Approval from the institutional animal care and use committee was obtained, and National Institutes of Health guidelines for the care and use of laboratory animals were observed. Dual-energy CT was performed in a set of iodine and tungsten solution phantoms and in a rabbit in which iodinated intravenous and bismuth subsalicylate oral contrast media were administered. In addition, a second rabbit was studied after intravenous administration of iodinated and tungsten cluster contrast media. Images were processed to produce virtual monochromatic images that simulated the appearance of conventional single-energy scans, as well as material decomposition images that separate the attenuation due to each contrast medium.. Clear separation of each of the contrast media pairs was seen in the phantom and in both in vivo animal models. Separation of bowel lumen from vascular contrast medium allowed visualization of bowel wall enhancement that was obscured by intraluminal bowel contrast medium on conventional CT scans. Separation of two vascular contrast media in different vascular phases enabled acquisition of a perfectly coregistered CT angiogram and venous phase-enhanced CT scan simultaneously in a single examination.. Commercially available clinical dual-energy CT scanners can help differentiate the enhancement of selected pairs of complementary contrast media in vivo.

Topics: Administration, Oral; Animals; Bismuth; Contrast Media; Feasibility Studies; Image Processing, Computer-Assisted; Injections, Intravenous; Iohexol; Organometallic Compounds; Phantoms, Imaging; Rabbits; Salicylates; Tomography, X-Ray Computed; Tungsten Compounds

The human gastric pathogen Helicobacter pylori steals host cholesterol, modifies it by glycosylation, and incorporates the glycosylated cholesterol onto its surface via a cholesterol glucosyltransferase, encoded by cgt. The impact of cholesterol on H. pylori antimicrobial resistance is unknown. H. pylori strain 26695 was cultured in Ham's F12 chemically defined medium in the presence or absence of cholesterol. The two cultures were subjected to overnight incubations with serial 2-fold dilutions of 12 antibiotics, six antifungals, and seven antimicrobial peptides (including LL-37 cathelicidin and human alpha and beta defensins). Of 25 agents tested, cholesterol-grown H. pylori cells were substantially more resistant (over 100-fold) to nine agents than were H. pylori cells grown without cholesterol. These nine agents included eight antibiotics and LL-37. H. pylori was susceptible to the antifungal drug pimaricin regardless of cholesterol presence in the culture medium. A cgt mutant retained cholesterol-dependent resistance to most antimicrobials but displayed increased susceptibility to colistin, suggesting an involvement of lipid A. Mutation of lpxE, encoding lipid A1-phosphatase, led to loss of cholesterol-dependent resistance to polymyxin B and colistin but not other antimicrobials tested. The cgt mutant was severely attenuated in gerbils, indicating that glycosylation is essential in vivo. These findings suggest that cholesterol plays a vital role in virulence and contributes to the intrinsic antibiotic resistance of H. pylori.

Topics: Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Cationic Peptides; Bacterial Proteins; Bismuth; Cathelicidins; Cell Wall; Cholesterol; DNA Replication; Drug Resistance, Bacterial; Folic Acid; Helicobacter pylori; Hydrophobic and Hydrophilic Interactions; Lipid A; Monomeric GTP-Binding Proteins; Organometallic Compounds; Phosphoric Monoester Hydrolases; Protein Synthesis Inhibitors; Salicylates

Topics: Bismuth; Chemistry Techniques, Synthetic; Crystallography, X-Ray; Ligands; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Organometallic Compounds; Salicylates

Topics: Antidiarrheals; Bismuth; Colitis; Colitis, Collagenous; Crohn Disease; Drug Therapy, Combination; Female; Humans; Loperamide; Middle Aged; Organometallic Compounds; Psychoses, Substance-Induced; Rectal Fistula; Salicylates; Steroids

Topics: Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Humans; Organometallic Compounds; Proton Pump Inhibitors; Salicylates

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Antidiarrheals; Biopsy; Bismuth; Budesonide; Ciprofloxacin; Colitis, Collagenous; Colonoscopy; Enema; Female; Humans; Intestinal Mucosa; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Treatment Outcome

A Mamastrovirus was identified in an outbreak of diarrhea in cheetahs (Acinonyx jubatus). Five young adult and two adult cheetahs presented with lethargy, anorexia, watery diarrhea and regurgitation over an 11-day period. Fecal samples were submitted for electron microscopy and culture. Electron microscopy results revealed particles morphologically consistent with an astrovirus, and no other viral pathogens or significant bacterial pathogens were identified. The astrovirus was confirmed and sequenced using consensus astroviral PCR, resulting in a 367 base pair partial RNA-dependent-RNA polymerase (RdRp) product and a 628 base pair partial capsid product. Bayesian and maximum likelihood phylogenetic analyses were performed on both the RdRp and the capsid protein segments. All animals were monitored and treated with bismuth subsalicylate tablets (524mg PO BID for 5 days), and recovered without additional intervention. This is the first report we are aware of documenting an astrovirus outbreak in cheetah.

Topics: Acinonyx; Animals; Antidiarrheals; Astroviridae; Astroviridae Infections; Base Sequence; Bismuth; Capsid Proteins; Disease Outbreaks; Feces; Female; Microscopy, Electron, Transmission; Molecular Sequence Data; Organometallic Compounds; Phylogeny; Reverse Transcriptase Polymerase Chain Reaction; RNA-Dependent RNA Polymerase; RNA, Viral; Salicylates; Vipoma

To observe the effects of fluid shear stress on carbonic anhydrase II in rat osteoclasts.. Osteoclasts were subject to fluid shear stress for 0,15,30,60 and 120 minutes respectively, which was 2.9dyne/cm(2). mRNA level of carbonic anhydrase II was detected through real-time fluorescent quantitation PCR. The data were analyzed with SPSS 12.0 software package.. mRNA level of carbonic anhydrase II in control group, 15 minutes,30 minutes,60 minutes and 120 minutes group was 7.88+/-0.09, 11.14+/-0.12, 15.83+/-0.18, 1.94+/-0.02, and 1.37+/-0.01(E+5 copy number), respectively. There was significant difference between any two groups (P<0.05).. In this present study, mRNA level of carbonic anhydrase II has an increasing tendency with various action times of fluid shear stress, it reaches to a peak value at 30 minutes. We speculated that there might be a certain time-effect relation between fluid shear stress and mRNA level of carbonic anhydrase II, but this mechanism need be further studied.

Topics: Animals; Bismuth; Carbonic Anhydrases; Cells, Cultured; Organometallic Compounds; Osteoclasts; Rats; RNA, Messenger; Salicylates; Stress, Mechanical

Topics: Adult; Anti-Bacterial Agents; Antidiarrheals; Atropine; Bismuth; Child; Cross-Sectional Studies; Diarrhea; Diphenoxylate; Drug Combinations; Dysentery; Fluid Therapy; Fluoroquinolones; Humans; Loperamide; Organometallic Compounds; Probiotics; Risk Factors; Salicylates; Travel

Contemporary total joint replacement designs contain stress-risers such as fillets, grooves, and undercuts; therefore, it is of interest to analyze the behavior of UHMWPEs in the presence of such design-related stress-risers. This study examined the engineering and true axial stress-strain behavior of smooth cylindrical and notched cylindrical test specimens, under applied axial tensile loading (2 displacement rates, 37 degrees C) for a conventional and a highly crosslinked second generation UHMWPE. Both materials were prepared from ram extruded GUR 1050. The conventional material (30 kGy) was gamma sterilized at 30 kGy in an inert N(2) environment. The sequentially annealed material (SA) was gamma irradiated at 30 kGy and annealed for 8h at 130 degrees C. The irradiation-annealing process was repeated two more times for an overall irradiation dose of 90 kGy. Differential scanning calorimetry (DSC) was utilized to investigate changes in crystallinity and lamellar thickness distributions upon loading. Fractographic analysis of scanning electron microscope (SEM) images of fracture surfaces was performed to investigate changes in fracture micromechanism with notching. Both the 30 kGy and SA materials, in the smooth condition, demonstrated substantial ductility and orientation hardening. With the introduction of a notch, both materials demonstrated an elevation in the yield stress (notch strengthening) and a reduction in the ultimate stress and ultimate strain at both displacement rates. Additionally, it was found that the uniaxial stress-state (smooth condition) allowed for greater changes in crystallinity and the lamellar thickness distributions, when compared to the untested materials, than the triaxial stress-state induced by the notched geometry.

Topics: Biocompatible Materials; Bismuth; Compressive Strength; Cross-Linking Reagents; Materials Testing; Organometallic Compounds; Polyethylenes; Prostheses and Implants; Salicylates; Tensile Strength

Analysis of many proteins produced during the transition into the stationary phase and under stress conditions (including starvation stress) demonstrated that a number of novel proteins were induced in common to each stress and could be the reason for cross-protection in bacterial cells. It is necessary to investigate the synthesis of these proteins during different stress conditions.. The changes in protein profile of Flexibacter chinensis at various stages of the starvation process and the other stresses were investigated using two-dimensional gel electrophoresis which has proven to be a powerful tool for investigation of the changes in protein profiles under such conditions.. Most starvation proteins were synthesized during the early stationary phase and many of these proteins remained during long-term starvation. Some of these proteins were transiently synthesized. The sequencing result of one of the proteins showed that there was a 62.5% identity in 8 amino acids overlapped with the 5' residue of a 10 kDa chaperon protein which is known to be involved in the starvation stress response in other organisms.. There are many proteins synthesized in common with many stresses in Flexibacter chinensis. Some of these proteins must play a major role in the stability of the cell under different stresses.

Topics: Amino Acid Sequence; Bacterial Proteins; Bismuth; Carbon; Electrophoresis, Gel, Two-Dimensional; Escherichia coli; Flexibacter; Gene Expression Regulation, Bacterial; Molecular Sequence Data; Nitrogen; Organometallic Compounds; Oxidative Stress; Phosphates; Salicylates; Temperature; Time Factors

Topics: Animals; Bismuth; Chelating Agents; Dog Diseases; Dogs; Female; Foreign Bodies; Organometallic Compounds; Radiography, Abdominal; Salicylates; Tablets; Treatment Outcome; Vomiting

The widespread use of bismuth compounds (e.g., bismuth subsalicylate, colloidal bismuth subcitrate) in medicine for over 200 years is founded on empirical observations, and definitive chemical mechanisms associated with the bioactivity of these compounds are not understood. The thiophilic nature of bismuth is a strong indication that sulfur-containing biological molecules are likely preliminary targets for bismuth. Using electrospray ionization mass spectrometry (ESI-MS), we have discovered a dramatic cooperative influence of thiolate ligands on the formation of bismuth complexes containing other biologically significant non-thiolate moieties. Reactions of Bi(NO3)3 with L-cysteine, 3-mercaptopropionic acid or 2-mercaptoethylamine, together with citric acid provide the first evidence of bismuth-citrate complexes in the gas phase. Analogously, reactions of Bi(NO3)3 with L-cysteine, together with other amino acids, reveal a wide range of new biologically relevant complex ions of bismuth that provide insight into the bioactivity of bismuth.

Topics: Amino Acids; Bismuth; Cysteine; Glycine; Molecular Structure; Organometallic Compounds; Picolinic Acids; Salicylates; Spectrometry, Mass, Electrospray Ionization; Sulfhydryl Compounds

Topics: Abdominal Pain; Adult; Bismuth; Constipation; Fecal Impaction; Humans; Male; Organometallic Compounds; Radiography; Salicylates

It has been proposed that eradication of Helicobacter pylori infection is a sound strategy for gastric cancer prevention. Several factors including smoking have been associated to treatment failure rates. This study aimed to evaluate the smoking effect on the efficacy of H. pylori therapy, as well as on the histological parameters in the gastric mucosa from subjects from a high gastric cancer risk area. Two-hundred-sixty-four Colombian subjects with gastric precancerous lesions who participated in a chemoprevention trial, received anti-H. pylori treatment at baseline and had data recorded on cigarette use, were included in this study. A detailed histopathological assessment of the gastric mucosa was performed in biopsies taken before any intervention. H. pylori eradication was assessed in gastric biopsies at 36 months post-treatment. The overall eradication rate was 52.3%; rates of 41.3% and 57.1% were observed for active-smokers and non-smokers, respectively. Multivariate logistic regression analysis showed that smokers had a 2-fold higher probability of failure in Helicobacter pylori eradication than non-smokers (OR: 2.0; 95% CI: 1.01-3.95). At baseline, active-smokers had a higher score of intestinal metaplasia compared to non-smokers. In the corpus mucosa, active-smokers showed lower scores of H. pylori density, total inflammation, neutrophil infiltration, and mucus depletion than non-smokers. In the antrum, no significant differences were observed between active-smokers and non-smokers. In summary, in patients who smoked, H. pylori treatment was less effective. Smoking cessation may benefit H. pylori eradication rates.

Topics: Amoxicillin; Anti-Infective Agents; Bismuth; Colombia; Drug Therapy, Combination; Female; Follow-Up Studies; Gastric Mucosa; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Metronidazole; Organometallic Compounds; Precancerous Conditions; Regression Analysis; Salicylates; Smoking; Treatment Failure

The complexation and sequestration of heavy metal ions (e.g. Cd) by the cysteine-rich polypeptides known as phytochelatins (PC) are thought to confer heavy metal hyperaccumulation and tolerance in some plant species. PC is synthesized enzymatically from glutathione. The tripeptide glutathione is a product of primary sulfur metabolism. A variety of enzymes or proteins are involved in sulfur assimilation including sulfate transporters (STs), ATP sulfurylase (ATPS), APS reductase (APSR), sulfite reductase (SiR), glutathione synthetase (GS) and phytochelatin synthesis (PCS). These enzymes or proteins are upstream-regulated by Cd at either the metabolic or the genetic level under metal stress. Increasing evidence shows that enhancement of sulfate uptake and reduction occurs with the production of PC in plants under heavy metal stress. In this article, the key aspects of our recent understanding of regulatory mechanisms involved in the relation between the sulfate assimilation and phytochelatin synthesis are described.

Topics: Bismuth; Cadmium; Gene Expression Regulation, Plant; Organometallic Compounds; Oxidoreductases Acting on Sulfur Group Donors; Phytochelatins; Plants; Salicylates; Sulfate Adenylyltransferase; Sulfates

Percy Medicine is a nonprescription gastrointestinal suspension containing bismuth subsalicylate as the active ingredient (1050 mg/10-ml dose). A 3-month-old infant with colic developed salicylate toxicity requiring hospitalization in the pediatric intensive care unit (PICU) as a result of continued administration of this medicine. Bismuth subsalicylate has an aspirin equivalency conversion factor of 0.479 (approximately half the strength of aspirin). For 3.5 weeks the infant's parents administered the medicine, which provided the equivalent of aspirin 57-84 mg/kg/day with no reported problems. However, on the day of admission the baby presented with central nervous system depression and respiratory distress. Assessment at a local emergency facility revealed metabolic acidosis; his serum salicylate concentration was 747 mg/L. After acute management, the patient was transferred to our hospital, where he was treated with whole bowel irrigation and alkalinization therapy. Subsequently, the baby required 4 days of management in the PICU and 2 additional days of observation in a general nursing unit before he was discharged home without incident. The parents had chosen Percy Medicine based on the picture of a baby on the front of the package and because of its placement on the shelf next to a drug their family physician had recommended previously. Salicylate-containing products are not routinely recommended for children aged 1 year or younger. The general public may assume that over-the-counter products are safe because they do not require a prescription. Health care professionals must be responsible for educating the public regarding risks associated with over-the-counter products and the need to read and follow label directions.

Topics: Bismuth; Colic; Humans; Infant; Male; Organometallic Compounds; Salicylates

We report a case of bismuth-induced pityriasis rosea-like drug eruption. Although historical accounts of bismuth hypersensitivity exist, contemporary reports are lacking. Given the frequency of bismuth administration, a modern review of this phenomenon would seem prudent.

Topics: Aged; Bismuth; Diagnosis, Differential; Drug Eruptions; Female; Humans; Organometallic Compounds; Pityriasis Rosea; Salicylates

Topics: Antibiotic Prophylaxis; Bismuth; Diarrhea; Humans; Organometallic Compounds; Salicylates; Travel

Topics: Anti-Ulcer Agents; Bismuth; Crystallography, X-Ray; Gastritis; Models, Molecular; Molecular Structure; Organometallic Compounds; Salicylates

Topics: Bismuth; Dentists; Drug-Related Side Effects and Adverse Reactions; Humans; Mouth Diseases; Organometallic Compounds; Professional Role; Salicylates; Tongue, Hairy

Triple therapy with bismuth subsalicylate, amoxicillin, metronidazole (BAM) or with omeprazole, amoxicillin, clarithromycin (OAC) has been commonly used for the eradication of Helicobacter pylori infection. We compared the efficacy of these triple therapies in children with H. pylori infection. We retrospectively analyzed results in 233 children with H. pylori infection and treated with OAC (n=141) or BAM (n=92). Overall eradication rates of triple therapy with OAC and BAM were 74% and 85%, respectively, which showed no statistical difference. Our study showed that the triple therapy with BAM was more effective for the first-line eradication of H. pylori infection in Korean children, but has no statistical difference with OAC regimen.

Topics: Adolescent; Amoxicillin; Anti-Bacterial Agents; Bismuth; Child; Child, Preschool; Clarithromycin; Drug Combinations; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Omeprazole; Organometallic Compounds; Retrospective Studies; Salicylates; Treatment Outcome

Bismuth subsalicylate (BSS), the active ingredient of Pepto-Bismol, has been used for many years to treat various disorders of the gastrointestinal tract. Using mass spectrometry and the agar dilution method, we determined that insoluble BSS interacts with certain dietary components and organic substrates to produce water-soluble products with activity against Clostridium difficile.

Topics: Anti-Bacterial Agents; Ascorbic Acid; Beverages; Bismuth; Clostridioides difficile; Drug Interactions; Fruit; Humans; Microbial Sensitivity Tests; Organometallic Compounds; Salicylates; Sulfhydryl Compounds

Enrichment cultures were conducted using bismuth subsalicylate as the sole source of carbon and activated sludge as the inoculum. A pure culture was obtained and identified as a Fusarium sp. based on spore morphology and partial sequences of 18S rRNA, translation elongation factor 1-alpha, and beta-tubulin genes. The isolate, named Fusarium sp. strain BI, grew to equivalent densities when using salicylate or bismuth subsalicylate as carbon sources. Bismuth nitrate at concentrations of up to 200 muM did not limit growth of this organism on glucose. The concentration of soluble bismuth in suspensions of bismuth subsalicylate decreased during growth of Fusarium sp. strain BI. Transmission electron microscopy and energy-dispersive spectroscopy revealed that the accumulated bismuth was localized in phosphorus-rich granules distributed in the cytoplasm and vacuoles. Long-chain polyphosphates were extracted from fresh biomass grown on bismuth subsalicylate, and inductively coupled plasma optical emission spectrometry showed that these fractions also contained high concentrations of bismuth. Enzyme activity assays of crude extracts of Fusarium sp. strain BI showed that salicylate hydroxylase and catechol 1,2-dioxygenase were induced during growth on salicylate, indicating that this organism degrades salicylate by conversion of salicylate to catechol, followed by ortho cleavage of the aromatic ring. Catechol 2,3-dioxygenase activity was not detected. Fusarium sp. strain BI grew with several other aromatic acids as carbon sources: benzoate, 3-hydroxybenzoate, 4-hydroxybenzoate, gentisate, d-mandelate, l-phenylalanine, l-tyrosine, phenylacetate, 3-hydroxyphenylacetate, 4-hydroxyphenylacetate, and phenylpropionate.

Topics: Biomass; Bismuth; Culture Media; Fusarium; Glucose; Microscopy, Electron, Transmission; Molecular Sequence Data; Organometallic Compounds; Peptide Elongation Factor 1; RNA, Ribosomal, 18S; Salicylates; Sequence Analysis, DNA; Tubulin

Topics: Bismuth; Diarrhea, Infantile; Fluid Therapy; Humans; Infant; Organometallic Compounds; Salicylates

Clinical and laboratory studies have shown that bismuth subsalicylate (BSS) is helpful in the healing of gastric ulcers because of the bactericidal effects of bismuth (Bi3+) on H. pylori. Bismuth or BSS has also been reported to possess other nonbactericidal or "gastroprotective" effects in the stomach. It is known in other cell types that the effects of extracellular divalent or trivalent cations (e.g., Ca2+) can activate a plasma membrane-bound calcium-sensing receptor (CaSR). In a previous study, we found the existence of a CaSR which was activated by extracellular Ca2+ and found to increase intracellular Ca2+ [Ca2+]i, MAP-kinase activity, and gastric epithelial cell proliferation. In the present study, we were interested in determining whether the effects of the trivalent cation Bi3+ (in the form of BSS) on [Ca2+]i, MAP-kinase activity, and proliferation of gastric cells. We found that BSS dose dependently increased [Ca2+]i, p44/p42 and p38 MAP-kinase activites, and gastric mucous epithelial cell growth. The addition of BAPTA to chelate intracellular Ca2+ blocked BSS-induced p44/p42 MAP-kinase activities but not p38 MAP-kinase activity. The p44/p42 MAP-kinase inhibitor PD98059 and the p38 MAP-kinase inhibitor SB203580 dose dependently decreased gastric mucous cell growth over a 24 hr. All of the BSS-induced changes in [Ca2+]i, MAP-kinase activity, and gastric cell proliferation could be reproduced with the CaSR-agonist gadolinium (Gd3+). Our data suggest that BSS may possess additional novel effects by increasing gastric mucous epithelial cell growth through a Ca2+/MAP-kinase-dependent pathway.

Topics: Acetates; Bismuth; Blotting, Western; Calcium; Calcium-Calmodulin-Dependent Protein Kinases; Cell Division; Cells, Cultured; Enzyme Activation; Enzyme Inhibitors; Epithelial Cells; Flavonoids; Gastric Mucosa; Humans; Imidazoles; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinases; Organometallic Compounds; p38 Mitogen-Activated Protein Kinases; Pyridines; Receptors, Calcium-Sensing; Salicylates; Signal Transduction

Collagenous colitis is a disorder that is recognized as a cause of chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This review was performed to identify therapies for collagenous colitis that have been proven in randomized trials.. To determine effective treatments for patients with clinically active collagenous colitis.. Relevant papers published between 1970 and October 2002 were identified via the MEDLINE, PUBMED, and EMBASE databases. Manual searches from the references of identified papers, as well as review papers on collagenous or microscopic colitis were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Finally, the Cochrane Controlled Trials Register and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were searched for other studies.. Four randomized trials were identified. One trial studied bismuth subsalicylate (published in abstract form only), and 3 trials (1 published in abstract form only) studied budesonide in the therapy of collagenous colitis.. Data were extracted independently by each author onto 2 x 2 tables (treatment versus placebo and response versus no response). For therapies assessed in one trial only, p-values were derived using the chi-square test. For therapies assessed in more than one trial, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals. Data were combined for analysis only if the outcomes were sufficiently similar in definition.. There were 9 patients with collagenous colitis in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks). Those randomized to active drug were more likely to have clinical (p = 0.003) and histological (p = 0.003) improvement than those assigned to placebo. A total of 94 patients were enrolled in 3 trials studying budesonide (9 mg daily for 6 to 8 weeks). The pooled odds ratio for clinical response to treatment with budesonide was 12.32 (95% CI 5.53-27.46), with a number needed to treat of 2 patients. There was significant histological improvement with treatment in all 3 trials studying budesonide therapy.. Budesonide is effective in the treatment of collagenous colitis. The evidence for bismuth subsalicylate is weaker, but still important. The roles of these and other therapies in inducing or maintaining remission (as opposed to clinical or histological improvement) of collagenous colitis are unknown.

Topics: Anti-Inflammatory Agents; Bismuth; Budesonide; Colitis; Evidence-Based Medicine; Humans; Meta-Analysis as Topic; Organometallic Compounds; Randomized Controlled Trials as Topic; Salicylates

Topics: Aged; Aged, 80 and over; Bismuth; Cecal Diseases; Cecum; Colonoscopy; Female; Humans; Organometallic Compounds; Radiography, Abdominal; Salicylates; Treatment Outcome

The synthesis and characterization of the first bismuth salicylate complexes, stabilized by chelating amine ligands, offers the possibility for detailed investigation of molecular precursors of the biologically significant compound bismuth subsalicylate (BSS).

Topics: Amines; Bismuth; Ligands; Models, Molecular; Molecular Structure; Organometallic Compounds; Phenanthrolines; Salicylates

Travelers' diarrhea is the most common health impairment in persons visiting developing countries, affecting 20% to >50% of tourists. Although it is usually benign, travelers' diarrhea represents a considerable socioeconomic burden for both the traveler and the host country. The most common enteropathogens are enterotoxigenic and enteroaggregative Escherichia coli. Travelers' compliance with dietary precautionary measures is poor. Despite the excellent protection rates provided by antibiotics, routine administration of prophylaxis is currently not recommended because of potential adverse reactions. Of the various antibiotics that have been tested, quinolones are considered to be the first choice worldwide; however, quinolone-resistant pathogens are increasingly being isolated. Because it is frequently administered and provides only moderate protection, bismuth subsalicylate is not considered a recommendable option for prophylaxis in Europe, where it is rarely available anyhow. To date, no probiotic has been able to demonstrate clinically relevant protection worldwide. In conclusion, there is no satisfactory prophylactic option, and worldwide monitoring of antimicrobial susceptibility patterns and the search for novel antimicrobial agents, such as nonabsorbed antibiotics, and nonantibiotic medications should continue.

Topics: 4-Quinolones; Anti-Infective Agents; Antibiotic Prophylaxis; Bismuth; Diarrhea; Escherichia coli Infections; Humans; Organometallic Compounds; Probiotics; Salicylates; Travel

We evaluated the effect of optimized doses and dosing schedules of metronidazole, tetracycline, and bismuth-metronidazole-tetracycline (BMT) triple therapy with only 1 day of dosing on Helicobacter pylori SS1 titers in a mouse model. A reduction of bacterial titers was observable with 22.5 and 112.5 mg of metronidazole per kg of body weight (as well as BMT) given twice daily and four times daily (QID). Two hundred milligrams of tetracycline per kilogram, given QID, resulted in only a slight reduction of H. pylori titers in the stomach. We argue that optimization of doses based on antimicrobial drug levels in the animal and shortened (1 or 2 days) drug administration can be used to facilitate early evaluation of putative anti-H. pylori drug candidates in lieu of using human doses and extended schedules (7 to 14 days), as can be deduced from the results seen with these antimicrobial agents.

Topics: Animals; Bismuth; Disease Models, Animal; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Mice; Mice, Inbred C57BL; Organometallic Compounds; Salicylates; Tetracycline

Topics: Adult; Anaphylaxis; Anti-Inflammatory Agents, Non-Steroidal; Bismuth; Drug Hypersensitivity; Humans; Immunoglobulin E; Male; Organometallic Compounds; Reproducibility of Results; Salicylates; Skin Tests; United States; Urticaria

Topics: Asthma; Bismuth; Female; Gastroesophageal Reflux; Humans; Lupus Erythematosus, Systemic; Middle Aged; Organometallic Compounds; Salicylates; Tongue Diseases

Topics: Amoxicillin; Antacids; Anti-Bacterial Agents; Bismuth; Chemoprevention; Colombia; Follow-Up Studies; Gastritis, Atrophic; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Penicillins; Precancerous Conditions; Salicylates; Stomach Neoplasms; Treatment Failure; Virulence

Our objectives were to define treatment success, compliance, and side effects for treatment of Helicobacter pylori in clinical practice. In all, 224 consecutive patients received Helicobacter pylori treatment: 97 received two weeks of bismuth subsalicylate, metronidazole, tetracycline four times a day with a H2-receptor antagonist twice a day (BMT); 89 received one week of metronidazole, lansoprazole, and clarithromycin twice a day (MLC); and 38 received one week of BMT with lansoprazole twice a day (BMT-PPI). Cure rates were: BMT 81% (95% CI 74-89%), MLC 90% (95% CI 84-96%) BMT-PPI 87% (95% CI 81-92%). More patients prescribed a bismuth-based regimen discontinued medications due to side effects compared to MLC (P = 0.049). Nausea was more common for BMT compared to MLC (P = 0.04). In conclusion, treatment of Helicobacter pylori infection with a one-week course of MLC achieves a high rate of cure in clinical practice. Significantly fewer patients prescribed PPI-based therapy discontinue medications due to side effects as compared to bismuth-based triple therapy.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Bacterial Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Proton Pump Inhibitors; Salicylates; Treatment Outcome; United States

The 2,4,6-trinitrobenzene sulfonic acid (TNBS) -induced model of chronic inflammation of the rat colon was used to determine the efficacy of bismuth subsalicylate (BSS), bismuth subcitrate (CBS), and 5-aminosalicylic acid (5-ASA) administered in enema form. A novel bismuth compound 1, 2-bis[2-(1,3-dithiobismolane)thio]ethane [Bi2(EDT)3] was also tested. On day 1 colitis was induced with 50 mg TNBS/50% ethanol in female Sprague-Dawley rats, while controls received a saline enema. On day 3, twice-daily treatment with enemas of either saline, BSS, CBS, Bi2(EDT)3, or 5-ASA were initiated in the colitis and control rats. All rats were killed on day 14, and the colons excised, weighed, rated macroscopically, and then fixed for hematoxylin and eosin staining. Blinded microscopic scoring was used to determine injury and healing in all groups. Colon mass and macroscopic scores were increased (P < 0.05) in the group of rats treated with TNBS (N = 16) compared to saline controls (N = 12). Colon mass and macroscopic scores in controls treated with BSS (N = 4), CBS (N = 4), Bi2(EDT)3 (N = 4), and 5-ASA (N = 4) alone did not differ from saline control animals. Macroscopic scoring showed a decrease (P < 0.05) in the degree of damage in the group of rats treated with TNBS plus BSS (N = 15), TNBS plus Bi2(EDT)3 (N = 10) and TNBS plus CBS (N = 4) compared to the group of rats treated with TNBS plus saline (N = 16). A decrease (P < 0.05) in injury and an increase (P < 0.05, Kruskal-Wallis) in healing was observed in the groups of rats treated with TNBS plus BSS, TNBS plus CBS, and TNBS plus 5-ASA compared to the group of rats treated with TNBS plus saline. It appeared that Bi2(EDT)3 was not protective against injury at the microscopic level but that the novel Bi2(EDT)3 has an effective healing capacity at the macroscopic level. We conclude that BSS and CBS decrease injury and/or promote healing as effectively as 5-ASA in this model.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Colitis; Female; Mesalamine; Organometallic Compounds; Rats; Rats, Sprague-Dawley; Salicylates; Trinitrobenzenesulfonic Acid

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bismuth; Cattle; Colonic Diseases, Functional; Dogs; Humans; Organometallic Compounds; Randomized Controlled Trials as Topic; Rats; Salicylates; Syndrome

Several lines of evidence suggest that ulcerative colitis could be caused by excessive bacterial production of H2S in the colon. A rodent model of colitis involves the feeding of nonabsorbable, carbohydrate-bound sulfate in the form of dextran sulfate or carrageenan. The observation that metronidazole blocks the development of this colitis suggested that the injurious agent could be a sulfur-containing compound (such as H2S) that is released during the bacterial metabolism of the nonabsorbed sulfate. We tested this possibility by feeding rats dextran sulfate, with or without bismuth subsalicylate, a compound that avidly binds H2S. Bismuth subsalicylate reduced the fecal release of H2S in dextran sulfate-treated rats to values well below that of controls. Nevertheless, all the animals developed colitis. We conclude that excessive H2S production does not play a role in the dextran sulfate model of colitis.

Topics: Animals; Bismuth; Colitis; Colon; Dextran Sulfate; Feces; Hydrogen Sulfide; Male; Organometallic Compounds; Rats; Rats, Sprague-Dawley; Reference Values; Salicylates

Poorly absorbed bismuth preparations may benefit a variety of chronic colonic conditions including ulcerative colitis. Bismuth-induced neurotoxicity is a potential complication of the chronic use of these preparations, and a less-absorbable form of bismuth is needed. If bismuth absorption occurs primarily in the upper gut, a delayed-release bismuth preparation could reduce absorption. We studied the site of bismuth absorption from bismuth subsalicylate (BSS) in rats. For 15 days, BSS (50 mg/day) was ingested or infused directly into the cecum via a chronically implanted cannula. Oral BSS resulted in serum and urine bismuth levels many times higher (3.5 +/- 0.3 microg/liter and 1,570 +/- 286 microg/g creatinine, respectively) than with cecal administration (undetectable (<1.5 microg/liter) and 75 +/- 25 microg/g creatinine). Thus, bismuth absorption from BSS occurred almost entirely in the upper gut. These findings provide a rationale for a similar study of delayed-release bismuth preparations in humans.

Topics: Absorption; Administration, Oral; Animals; Bismuth; Cecum; Colonic Diseases; Creatinine; Injections; Male; Organometallic Compounds; Rats; Rats, Sprague-Dawley; Salicylates

Topics: Aged; Biopsy; Bismuth; Colitis; Collagen; Colon; Female; Humans; Organometallic Compounds; Salicylates

Acinetobacter baumannii is an opportunist nosocomial pathogen of world-wide importance and produces severe infections in immunocompromised patients. However, the virulence factors contributing to its pathogenic properties are not well known. The effect of normal human serum against 18 clinical isolates of the most prevalent biotypes of A. baumannii in Chile was investigated. The effect of pre-treatment of the cells with ethylene diamine tetraacetic acid (EDTA) or bismuth subsalicylate (BSS), compounds known to decrease the amount of lipopolysaccharide (LPS) and bacterial capsular polysaccharide (CPS), respectively, in other gram-negative bacteria, was evaluated. Most isolates (16 of 18) showed resistance to normal human serum. Prior treatment with EDTA rendered nine of these isolates susceptible to serum, while seven isolates maintained their resistance. Pre-treatment with BSS did not modify the serum-resistant behaviour of the isolates. The results suggest that LPS might be involved in the resistance of A. baumannii to human serum whereas CPS does not seem to contribute to this property.

Topics: Acinetobacter; Bacterial Capsules; Bismuth; Blood Bactericidal Activity; Chelating Agents; Edetic Acid; Humans; Lipopolysaccharides; Organometallic Compounds; Salicylates

Topics: Acute Disease; Bismuth; Child; Child, Preschool; Evidence-Based Medicine; Gastroenteritis; Humans; Infant; Organometallic Compounds; Safety; Salicylates; Treatment Outcome

Bismuth compounds remain useful for Helicobacter pylori eradication therapy. These include colloidal bismuth subcitrate (CBS), bismuth subsalicylate (BSS) and, most recently, ranitidine bismuth citrate (RBC). CBS appears to prevent the development of imidazole resistance when coadministered with nitroimidazoles. Traditional triple therapy with bismuth, metronidazole and tetracycline or amoxicillin (BMT/A) only partially overcomes metronidazole resistance. However, the addition of a PPI to bismuth triple therapy largely overcomes established metronidazole resistance if treatment is given for at least one week or more. When RBC rather than PPI is used with clarithromycin, this dual regimen appears to be more effective in preventing the development of secondary clarithromycin resistance. The triple combination of RBC, metronidazole and clarithromycin appears to be effective against metronidazole resistant strains of H pylori. Thus, overall, there is some evidence that bismuth compounds may prevent the development of antibiotic resistance and that existing antibiotic resistance may at least be partially overcome in vitro and in vivo. With the growing emergence of H pylori resistance to metronidazole and clarithromycin, further research to clarify the role of bismuth compounds is required.

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Clarithromycin; Drug Resistance, Microbial; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Ranitidine; Salicylates

Rhesus monkeys, naturally colonized with H. pylori as indicated by culture and histology were immunized with either 40 mg recombinant H. pylori urease administered orally together with 25 microg Escherichia coli heat-labile enterotoxin (LT) or immunized with LT alone. An initial 6 doses were administered over an 8 week period. All five vaccinated monkeys had a greater than two-fold rise in urease-specific serum IgG and IgA level and urease-specific salivary IgA was induced in 3 of 5 vaccinated animals after 6 or 7 doses of vaccine. Vaccination had no measurable therapeutic effect on H. pylori colonization. H. pylori was eradicated from these monkeys with a course of antimicrobials plus omeprazole, a 7th vaccine dose was given (10 months after the 6th dose) and they were rechallenged with H. pylori. Necropsy was performed 23 weeks after rechallenge and H. pylori colonization was determined by histological examination of 12 individual gastric sites. A significant reduction in colonization (p < or = 0.0001; Friedman's analysis of variance) was found in the vaccinated animals. Histopathologic examination of necropsy tissues also revealed a trend towards reduced gastritis and epithelial alterations in the vaccinated group compared to animals receiving LT alone. This study provides the first evidence for effective vaccination of nonhuman primates against H. pylori, and preliminary evidence that a reduction in bacterial density attributable to immunization may lessen gastric inflammation.

Topics: Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Bacterial Toxins; Bacterial Vaccines; Bismuth; Clarithromycin; Drug Therapy, Combination; Enterotoxins; Enzyme-Linked Immunosorbent Assay; Escherichia coli Proteins; Helicobacter Infections; Helicobacter pylori; Macaca mulatta; Metronidazole; Omeprazole; Organometallic Compounds; Recombinant Proteins; Salicylates; Saliva; Urease

Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is related to Helicobacter pylori infection and may depend on this infection for growth.. To determine the response of gastric MALT lymphoma to antibiotic treatment.. Prospective, uncontrolled treatment trial.. University hospital referral center and three collaborating university and community hospitals.. 34 patients with stage I or stage II N1 gastric MALT lymphoma.. Two of three oral antibiotic regimens--1) amoxicillin, 750 mg three times daily, and clarithromycin, 500 mg three times daily; 2)tetracycline, 500 mg four times daily, and clarithromycin, 500 mg three times daily; or 3) tetracycline, 500 mg four times daily, and metronidazole, 500 mg three times daily--were administered sequentially (usually in the order written) for 21 days at baseline and at 8 weeks, along with a proton-pump inhibitor (lansoprazole or omeprazole) and bismuth subsalicylate.. Complete remission was defined as the absence of histopathologic evidence of lymphoma on endoscopic biopsy. Partial remission was defined as a reduction in endoscopic tumor stage or 50% reduction in the size of large tumors.. 34 patients were followed for a mean (+/-SD) of 41 +/- 16 months (range, 18 to 70 months) after antibiotic treatment. Of 28 H. pylori-positive patients, 14 (50% [95% CI, 31% to 69%]) achieved complete remission, 8 (29%) achieved partial remission (treatment eventually failed in 4 of the 8), and 10 (36% [CI, 19% to 56%]) did not respond to treatment. Treatment failed in all 6 (100% [CI, 54% to 100%]) H. pylori-negative patients. Patients with endoscopic appearance of gastritis (stage I T1 disease) were most likely to achieve complete remission within 18 months. Tumors in the distal stomach were associated with more favorable response than tumors in the proximal stomach.. A subset of H. pylori-positive gastric MALT lymphomas, including infiltrative tumors, may respond to antibiotics. The likelihood of early complete remission seems to be greatest for superficial and distal tumors.

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Lymphoma, B-Cell, Marginal Zone; Neoplasm Staging; Omeprazole; Organometallic Compounds; Prospective Studies; Remission Induction; Salicylates; Stomach Neoplasms

Reactive oxygen species (ROS) are implicated in the pathogenesis of stress-induced gastrointestinal mucosal injury. In the present study, we have investigated the effects of acute and chronic stress on the enhanced production of ROS including superoxide anion [SA; as determined by cytochrome c reduction (CCR)] and hydroxyl radicals (OH), and correlated the enhanced production of these free radicals with increased lipid peroxidation, membrane microviscosity and DNA fragmentation, indices of oxidative tissue damage, in the gastric and intestinal mucosa of female Sprague-Dawley rats. Furthermore, the protective ability of bismuth subsalicylate (BSS) against the gastrointestinal mucosal injury induced by acute and chronic stress was determined. Acute stress was induced for a period of 90 min, while chronic stress was induced for 15 min/day for 15 consecutive days. Half of the animals exposed to acute stress were pretreated orally with 15 mg BSS/kg 30 min prior to the exposure to acute stress. Similarly, half of the animals exposed to water-immersion restraint chronic stress were pretreated orally with 7.5 mg BSS/kg/day for 15 consecutive days 30 min prior to the exposure to chronic stress. Acute stress produced greater injury to both gastric and intestinal mucosa as compared to chronic stress. Acute stress increased CCR and OH production by 10.0- and 14.3-fold, respectively, in the gastric mucosa, and 10.4- and 17.0-fold, respectively, in the intestinal mucosa. Pretreatment with BSS prevented the acute stress-induced increase in CCR and OH production. Acute stress increased lipid peroxidation, DNA fragmentation and membrane microviscosity by 3.6-, 4.0- and 11.6-fold, respectively, in gastric mucosa, and 4.1-, 5.0- and 16.2-fold, respectively, in intestinal mucosa. BSS decreased acute stress-induced lipid peroxidation, DNA fragmentation and membrane microviscosity by approximately 26, 35 and 30%, respectively, in gastric mucosa, and by 20, 36 and 30%, respectively, in the intestinal mucosa. Chronic stress increased CCR and OH production by 4.8- and 6.3-fold, respectively, in gastric mucosa, and 4.6- and 6.9-fold, respectively, in intestinal mucosa. Chronic stress increased lipid peroxidation and DNA fragmentation by 2.9- and 3.3-fold, respectively, in gastric mucosa, and 3.3- and 4.2-fold, respectively, in intestinal mucosa. BSS decreased chronic stress-induced lipid peroxidation, DNA fragmentation and membrane microviscosity by approximately 41, 44 and 45%, r

Topics: Animals; Bismuth; DNA Fragmentation; Female; Hydroxyl Radical; Intestinal Mucosa; Lipid Peroxidation; Organometallic Compounds; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Salicylates; Stress, Physiological; Viscosity

This study was designed to investigate whether acid suppression and bismuth medications interfere with the performance of diagnostic tests for Helicobacter pylori (H. pylori) infection.. Sixty patients with previous diagnoses of atrophic gastritis and H. pylori infection made in gastric biopsies taken at Hospital Departmental, Pasto, Colombia, were enrolled in the study. 13C breath urea test (UBT) and stool antigen test (HpSA) were performed simultaneously. Two baseline tests were performed: one 7 days before and another the day before starting medications. A total of 20 patients received for 2 wk one of the following treatments: a) ranitidine; b) lansoprazole; or c) bismuth subsalicylate. The tests were repeated while the patients were on the prescribed medication on days 7 and 14 and then 2 wk after finishing the medication.. Utilizing standard cut-off values for the tests, our results indicate that in the case of the 13C UBT test, ranitidine does not interfere with the results, whereas lansoprazole and bismuth may be expected to yield a significant proportion of false negative results (30-40% for lansoprazole and 45-55% for bismuth). In the case of the HpSA test, ranitidine does not interfere, whereas lansoprazole and bismuth may be expected to yield a nonsignificant proportion of false negative results (15-25% for lansoprazole and 10-15% for bismuth). Absolute values for both tests may be used to study the effects of the pharmacological agents on the characteristics of the infection.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Antigens, Bacterial; Bismuth; Breath Tests; Feces; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Omeprazole; Organometallic Compounds; Ranitidine; Salicylates; Sensitivity and Specificity; Urea

Helicobacter pylori (H. pylori) infection has been linked to gastric cancer. The factors that promote carcinogenesis remain unknown. Epidermal growth factor (EGF) has been shown to be a potent epithelial mitogen and oncoprotein when sustained over expression occurs. Our aim was to compare gastric mucosal levels of EGF and its receptor (EGFR) among controls, H. pylori infected subjects, and subjects following H. pylori eradication using quantitative flow cytometric analysis.. Patients referred for evaluation of dyspepsia underwent EGD and six antral biopsies were performed (two each for rapid urease testing (RUT), histopathology, and flow cytometry). Controls were those found to be H. pylori negative while subjects had confirmed infection. The study patients were treated, then had repeat EGD with biopsies.. There were 17 controls and 28 cases. Mean EGF and EGFR values were 2.69 and 2.46 for controls and 4.67 and 4.64 for subjects. Subjects' mean EGF was 73% higher (p = .035) and EGFR was 88% higher (p = 0.029) than controls. After treatment, the subjects' mean values declined 55% (p = 0.0001) for EGF and 40% (p = 0.002) for EGFR. Three subjects had persistent infection and showed no change in their EGF/EGFR levels. No difference was found among factor levels with respect to endoscopic findings.. Both EGF and EGFR from gastric antral biopsies are increased nearly 2-fold in infection with H. pylori. Infection eradication reduces levels of both factors to those of controls. One major pathogenic mechanism for gastric mucosal hyperproliferation and possibly carcinogenesis related to H. pylori may be the over expression of EGF and increased receptor density of EGFR on gastric mucosal cells.

Topics: Adult; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Biopsy; Bismuth; Chronic Disease; Drug Therapy, Combination; Epidermal Growth Factor; ErbB Receptors; Female; Flow Cytometry; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Organometallic Compounds; Prospective Studies; Salicylates

Microscopic colitis is a syndrome consisting of chronic watery diarrhea, a normal or near-normal gross appearance of the colonic lining, and a specific histological picture described as either lymphocytic colitis or collagenous colitis. Since its initial descriptions a quarter of a century ago, microscopic colitis has become a frequent diagnosis in patients with chronic diarrhea. Understanding of the cause and pathogenesis of microscopic colitis remain incomplete, but potentially important clues have been discovered that shed light on predisposing factors. In particular, specific HLA-DQ genotypes may be permissive for the development of microscopic colitis, and suggest a linkage to the pathogenesis of celiac sprue. Although the differential diagnosis of chronic watery diarrhea is broad, the diagnosis of microscopic colitis is straightforward, involving endoscopic inspection of the colonic mucosa and proper pathologic interpretation of biopsy specimens. As the limitations of drugs ordinarily used for other forms of inflammatory bowel disease are being recognized, new approaches, such as the use of bismuth subsalicylate, are being evaluated. The prognosis of patients with microscopic colitis syndrome remains good, and symptomatic improvement can be expected in most patients.

Topics: Adult; Bismuth; Chronic Disease; Colitis; Colonoscopy; Diagnosis, Differential; Diarrhea; Female; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Organometallic Compounds; Pancreatic Neoplasms; Prognosis; Salicylates; Vipoma

Helicobacter pylori can be eradicated by administration of antimicrobials, but resistant strains have emerged, and there is a need for novel therapeutic approaches against this infection. This study aimed to determine the safety and efficacy of 3'-sialyllactose sodium salt (3'SL), an oligosaccharide that occurs naturally in human and bovine milk and that can inhibit the adhesion of H. pylori to human epithelial cells in vitro.. Twelve H. pylori-positive rhesus monkeys were given 3'SL, either alone (regimens 1 and 2; n = 6) or in combination with omeprazole (regimen 3; n = 4), or bismuth subsalicylate (regimen 4; n = 6). Videogastroscopies were performed before, during, and after treatment, and gastric biopsy specimens were obtained for quantitative cultures and histology. The H. pylori strains colonizing the animals were genotyped.. After regimen 1 or 2, 2 of 6 animals were cured permanently, and a third animal was transiently cleared. The 3 other animals remained persistently colonized and did not respond to regimen 3. Regimen 4 resulted in transient decreases in colony counts in 3 of 6 other animals. Gastritis was suppressed only in the 2 animals who became persistently H. pylori negative. There was no apparent relation between 3'SL efficacy and any of the H. pylori tested genotypes. No side effects were observed in any of the animals receiving 3'SL.. Antiadhesive therapy is safe; it can cure or decrease H. pylori colonization in some rhesus monkeys, but the addition of a proton pump inhibitor or bismuth subsalicylate does not increase cure rate.

Topics: Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Disease Models, Animal; Drug Therapy, Combination; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Lactose; Liver Function Tests; Macaca mulatta; Organometallic Compounds; Proton Pump Inhibitors; Salicylates; Sialic Acids

Topics: Adult; Amoxicillin; Anti-Ulcer Agents; Autoimmune Diseases; Bismuth; Drug Therapy, Combination; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; L-Lactate Dehydrogenase; Metronidazole; Omeprazole; Organometallic Compounds; Purpura, Thrombocytopenic, Idiopathic; Salicylates; Tetracycline

Reactive oxygen species (ROS) are implicated in the pathogenesis of chemically induced gastric mucosal injury. We have investigated the effects of ethanol, hydrochloric acid (HCl), and sodium hydroxide (NaOH) on: (1) enhanced production of ROS including superoxide anion and hydroxyl radicals, (2) modulation of intracellular oxidized states by laser scanning confocal microscopy, and (3) DNA fragmentation, indices of oxidative tissue, and DNA damage in a primary culture of normal human gastric mucosal cells (GC), which were isolated and cultured from Helicobacter pylori-negative endoscopic biopsies from human subjects. The induction of ROS and DNA damage in these cells following exposure to ethanol (15%), HCl (150 mM) and NaOH (150 mM) were assessed by cytochrome c reduction (superoxide anion production), HPLC detection for enhanced production of hydroxyl radicals, changes in intracellular oxidized states by laser scanning confocal microscopy, and DNA damage by quantitating DNA fragmentation. Furthermore, the protective ability of bismuth subsalicylate (BSS) was assessed at concentrations of 25, 50, and 100 mg/liter. Incubation of GC with ethanol, HCI, and NaOH increased superoxide anion production by approximately 8.0-, 6.1-and 7.1-fold and increased hydroxyl radical production by 13.3-, 9.6-, and 8.9-fold, respectively, compared to the untreated gastric cells. Incubation of GC with ethanol, HCl, and NaOH increased DNA fragmentation by approximately 6.7-, 4.3-, and 4.8-fold, respectively. Approximately 20.3-, 17.5-, and 13.1-fold increases in fluorescence intensities were observed following incubation of gastric cells with ethanol, HCl, and NaOH, respectively, demonstrating dramatic changes in the intracellular oxidized states of GC following exposure to these necrotizing agents. Preincubation of GC with 25, 50, and 100 mg/liter of BSS decreased ethanol-induced increases in intracellular oxidized states in these cells by 36%, 56%, and 66%, respectively, demonstrating a concentration-dependent protective ability by BSS. Similar results were observed with respect to BSS in terms of superoxide anion and hydroxyl radical production, and DNA damage. The present study demonstrates that ethanol, HCl, and NaOH induce oxidative stress and DNA damage in GC and that BSS can significantly attenuate gastric injury by scavenging these ROS.

Topics: Bismuth; Cells, Cultured; Cytochrome c Group; DNA Damage; DNA Fragmentation; Ethanol; Gastric Mucosa; Humans; Hydrochloric Acid; Microscopy, Confocal; Organometallic Compounds; Oxidative Stress; Reactive Oxygen Species; Salicylates; Sodium Hydroxide; Stomach; Superoxides

Rhesus monkeys raised in colonies tend to become naturally infected by Helicobacter pylori early in life. Earlier attempts to cure H. pylori infection with a 10-day triple therapy (metronidazole, amoxicillin, and peptobismol) were only partially (60%) successful, probably because of preexisting metronidazole resistance. This study was carried out to determine the efficacy of an alternative clarithromycin-omeprazole-based therapy for curing H. pylori infection in Rhesus monkeys (Macaca mulatta), and to examine histologic and serologic correlates of curing. Five monkeys were endoscoped under ketamine anesthesia. Histology and culture of gastric biopsies and serologic tests demonstrated that they were H. pylori-positive. Two animals had not received prior anti-H. pylori treatment, while three other animals had failed triple therapy and carried metronidazole-resistant H. pylori strains. Quadruple therapy with omeprazole, clarithromycin, amoxicillin, and bismuth subsalicylate was given for 10 days to these five animals. All five animals were cured of the infection, and remained H. pylori-free, based on histology and culture at regular intervals for the 5 months posttherapy during which they were followed. Gastritis scores and anti-H. pylori IgG levels decreased in each animal during this period to levels characteristic of uninfected animals. These results indicate that an omeprazole-clarithromycin-based regimen can cure H. pylori infection in Rhesus monkeys, with resolution of abnormal histology and serologic responses. They suggest that this preclinical animal model is useful for testing new anti-H. pylori therapies.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Enzyme Inhibitors; Gastritis; Helicobacter Infections; Helicobacter pylori; Macaca mulatta; Male; Omeprazole; Organometallic Compounds; Penicillins; Salicylates

Topics: Bismuth; Drug Interactions; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Peptic Ulcer; Salicylates; Tetracycline

Hydrogen sulfide is one of the main malodorous compounds in human flatus. This toxic gas also has been implicated in the pathogenesis of ulcerative colitis. Therefore, a treatment that reduces colonic H2S levels could be clinically useful in the treatment of flatus odor and of ulcerative colitis. In this study the ability of bismuth subsalicylate, a compound that binds H2S, to reduce H2S release in the colon, was tested.. Homogenates made from human and rat feces were incubated with and without bismuth subsalicylate, and gas production was measured. Fecal samples from 10 healthy subjects were analyzed before and after ingestion of bismuth subsalicylate (524 mg four times a day) for 3-7 days.. Fecal homogenates showed a dose-dependent relationship between the concentration of bismuth subsalicylate and H2S release. Treatment of subjects with bismuth subsalicylate produced a >95% reduction in fecal H2S release.. The ability of bismuth subsalicylate to dramatically reduce H2S could provide a clinically useful means of controlling fecal and/or flatus odor and of decreasing the putative injurious effects of H2S on the colonic mucosa.

Topics: Adult; Animals; Bismuth; Colon; Dose-Response Relationship, Drug; Feces; Female; Humans; Hydrogen Sulfide; Male; Middle Aged; Organometallic Compounds; Osmolar Concentration; Rats; Salicylates

Topics: Bismuth; Colitis, Ulcerative; Humans; Hydrogen Sulfide; Organometallic Compounds; Salicylates

Risk factors for travelers' diarrhea include adventurous behavior, consumption of unclean water or food, and special hosts like those taking long acting H2 blockers. Approaches to prevention include education about risk factors, which often fails to lead to modification of risky behavior, and chemoprophylaxis with bismuth subsalicylate-containing compounds or antimicrobial agents. Chemoprophylaxis is generally discouraged except in special circumstances and in high-risk hosts. Self-treatment of travelers' diarrhea is successful in limiting the course of diarrhea and minimizing losses of vacation and business time. Current therapeutic options, in order of increasing effectiveness, include attapulgite, BSS-containing compounds, loperamide, antimicrobial agents such as the fluoroquinolones, and the combination of loperamide and an antimicrobial agent. Under study are a nonabsorbed antimicrobial agent, rifaximin, and a novel calmodulin inhibitor, zaldaride. Development and evaluation of vaccines against enterotoxigenic Escherichia coli and Shigella are proceeding apace but are not yet available for routine use.

Topics: Antidiarrheals; Bismuth; Diarrhea; Food Microbiology; Humans; Organometallic Compounds; Salicylates; Self Care; Travel; Water Microbiology

The mechanism by which dietary pepper causes dyspepsia and epigastric pain is poorly understood, as is the ability of bismuth subsalicylate (BSS) to relieve these symptoms.. To investigate the ability of black pepper, red pepper and BSS to affect gastric surface hydrophobicity and induce/relieve visceral pain in rat model systems.. Fasted rats were administered intragastrically Vivonex containing varying concentrations of either black or red pepper (0-200 mg/mL) and gastric contact angles were read after 1-24 h. Some rats were post-treated with BSS (2.0-17.5 mg/mL) and contact angles were read after 2-18 h. To study pain sensitivity in rats treated with pepper/BSS, we compared tail-flick latencies after the application of radiant heat.. Both black and red pepper rapidly (< 1 h) induced a decrease in gastric surface hydrophobicity in a dose-dependent fashion. This spice-induced increase in surface wettability was long-lasting, could be enhanced in the presence of ethanol and reversed by post-treating the rats with BSS. Both black and red pepper induced an increase in pain sensitivity, consistent with the presence of gastric pain, which could also be reversed by post-treating the rats with BSS.. Both black and red pepper may induce epigastric pain by removing the stomach's hydrophobic lining and activating intramucosal pain receptors. BSS may provide relief from postprandial dyspepsia by restoring the stomach's non-wettable properties.

Topics: Animals; Bismuth; Chemical Phenomena; Chemistry, Physical; Diet; Dose-Response Relationship, Drug; Gastric Acid; Gastric Mucosa; Male; Organometallic Compounds; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Regression Analysis; Salicylates; Spices; Stomach Diseases; Surface Properties

Topics: Bacterial Infections; Bismuth; Child; Gastric Mucosa; Gastritis; Helicobacter heilmannii; Humans; Male; Metronidazole; Organometallic Compounds; Salicylates; Tetracycline

Helicobacter pylori infection of the stomach is being detected and treated more often now than ever before. This is likely to result in an increase in complications such as antibiotic-associated diarrhea. However, there is no literature on the incidence of such diarrhea, particularly Clostridium difficile colitis, in patients treated for Helicobacter pylori infection. We report the case of a patient who developed Clostridium difficile colitis after treatment for Helicobacter pylori infection with metronidazole, amoxicillin, H2 blockers, and bismuth subsalicylate. This patient presented with severe diarrhea that responded to a course of metronidazole with rapid disappearance of symptoms. The incidence of Clostridium difficile colitis in patients treated for Helicobacter pylori infection has not been studied. This unique association, although not unexpected, has not yet been reported in the literature. The increasing number of patients being diagnosed and treated for this infection requires a heightened awareness on the part of physicians, to assure early diagnosis and treatment of this treatable, yet potentially dangerous, complication.

Topics: Aged; Amoxicillin; Anti-Bacterial Agents; Bismuth; Clostridioides difficile; Diarrhea; Enterocolitis, Pseudomembranous; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metronidazole; Organometallic Compounds; Penicillins; Salicylates; Stomach Diseases

To determine the pharmacoeconomic impact of antimicrobial treatment of peptic ulcer disease (PUD) in a large urban jail.. Retrospective comparison of PUD-related pharmacy and laboratory expenditures over a 2-year period before and after the institution of a PUD treatment protocol with the priority of Helicobacter pylori eradication for inmates in Rikers Island Correctional Facility.. After the protocol was adopted, total pharmacy-related and laboratory-related expenses for PUD care decreased by 40.2%, and expenditures for ranitidine declined by 52.2%. There was an increase in spending for antimicrobial agents and H. pylori antibody testing, but this was insignificant compared to the savings generated by decreased ranitidine usage. Annual savings in our facility as a result of this intervention were $123,449.. Modern therapeutic strategies for PUD aimed at eradicating H. pylori can result in significant savings in the institutional setting; these savings are largely attributable to the decreased usage of histamine-2 receptor antagonists.

Topics: Adult; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Metronidazole; New York City; Organometallic Compounds; Peptic Ulcer; Prisons; Ranitidine; Retrospective Studies; Salicylates; Tetracycline; Urban Health

Acinetobacter baumannii, an important nosocomial pathogen, causes severe infections in patients of intensive care units, but its pathogenic attributes are unknown. Previously, the adherence of A. baumannii to cell lines has been negative in the authors' laboratory. In this work, the adherence of strains of A. baumannii of various biotypes to small pieces of rat bladder tissue was investigated. Tissue pieces were submerged into cultures of A. baumannii and sessile cells were counted after removing planktonic bacteria. Fimbriae and sessile cells were examined by transmission and scanning electron microscopy, respectively. In contrast to a uropathogenic strain of Escherichia coli, all cultures exhibited a mannose- and galactose-resistant agglutination of human group O red blood cells as well as mannose- and galactose-resistant adherence to the bladder tissue. Inhibition of exopolysaccharide synthesis did not modify adherence. Indeed, adherence, apparently unrelated to these fimbriae or to the exopolysaccharide, may be a factor contributing to the pathogenicity of A. baumannii in the urinary tract or in other tissues.

Topics: Acinetobacter; Animals; Bacterial Adhesion; Bismuth; Cells, Cultured; Escherichia coli; Galactose; Humans; Mannose; Microscopy, Electron; Organometallic Compounds; Polysaccharides; Rats; Rats, Sprague-Dawley; Salicylates

The absorption of bismuth from De-Nol (bismuth subcitrate, DN), Pepto-Bismol (bismuth subsalicylate, PB) and bismuth sucrose octasulfate (BISOS) was examined in male Sprague-Dawley rats after a single oral dose of each compound (60mg bismuth). Bismuth was analysed in blood, urine, kidney, brain, liver, and lung using graphite furnace atomic absorption spectrophotometry. Bismuth Cmax averaged 18.4 +/- 11.6 ng mL(-1) for BISOS, 292 +/- 130 ng mL(-1) for DN, and 21.5 +/- 9.63 ng mL(-1 ) for PB. Cmax was significantly lower for BISOS compared to DN (p<0.05) but not significantly different for BISOS compared to PB (p > 0.05). Bismuth AUC was 1356 +/- 474 ng h(-1) mL (-1) for BISOS, 2129 +/- 452 ng h(-l) mL(-1) for DN, and 1824 +/- 919 ng h(-1) for PB, which indicated a lower extent of absorption from BISOS compared to DN. Kidney, liver, and lung levels of bismuth were also significantly lower for BISOS compared to DN (p < 0.05). Bismuth urinary excretion was significantly lower for BISOS (0.04 +/- 0.02%) compared to DN (0.27 +/- 0.15%) but not significantly different compared to PB (0.07 +/- 0.03%). These data suggest that the absorption of bismuth following oral administration of bismuth sucrose octasulfate is significantly lower than that from De-Nol and similar to that from Pepto-Bismo.

Topics: Administration, Oral; Animals; Antacids; Area Under Curve; Bismuth; Intestinal Absorption; Male; Organometallic Compounds; Rats; Rats, Sprague-Dawley; Salicylates; Spectrophotometry, Atomic; Sucrose; Tissue Distribution

Helicobacter pylori has been proposed as a major determinant in multiple gastric disorders. We describe the case of a young adult with a long-standing medical history of sideropenic anaemia and of oral iron consumption dependence with a chronic superficial H. pylori-positive gastritis. All other causes of sideropenic anaemia were carefully excluded. Histology showed a peculiar pattern of non-active H. pylori-positive gastritis. The bacterium was a non-VacA-producing strain. The first attempt at eradication caused a reduction in bacterial load and led to a partial normalization of haematologic variables without improving the ferritin level. A successful second course of eradication therapy completely reversed the anaemia and restored the iron deposit, which persisted at the 29-month follow-up. H. pylori infection can be involved in unexplained cases of iron deficiency anaemia in adults, and its cure can normalize the haematologic picture.

Topics: Adult; Anemia, Iron-Deficiency; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Omeprazole; Organometallic Compounds; Salicylates; Tetracycline

The activity of clarithromycin-14-hydroxyclarithromycin (2:1 ratio) and bismuth subsalicylate or amoxicillin against Helicobacter pylori was determined by the checkerboard technique in vitro. Clarithromycin-14-hydroxyclarithromycin and amoxicillin resulted in additive effects in 7 of 22 isolates, compared to 14 of 22 isolates when bismuth subsalicylate was substituted for amoxicillin. Synergy was not demonstrated and is probably not responsible for the clinical success of treatment combinations containing clarithromycin.

Topics: Amoxicillin; Bismuth; Clarithromycin; Drug Synergism; Drug Therapy, Combination; Helicobacter pylori; Microbial Sensitivity Tests; Organometallic Compounds; Salicylates

Bismuth compounds prevent gastric injury from the short-term administration of nonsteroidal anti-inflammatory drugs. We studied the mechanisms underlying the gastroprotective actions of bismuth subsalicylate against indomethacin-induced injury in rats.. An in vivo microscopic technique was used in which acid output, surface cell intracellular pH (pHi), gastric mucus gell thickness and mucosal blood flow were measured simultaneously. Concentrations of bismuth in mucus were measured by atomic absorption.. Indomethacin (60 mg/kg) significantly thinned the mucus gel layer and augmented the decrease of pHi during luminal acid superfusion, consistent with a weakened gastric mucosal barrier to acid. Bismuth subsalicylate partially reversed this effect of indomethacin on pHi, consistent with gastroprotection. Neither a prostaglandin-inhibiting but non-injurious dose of indomethacin (5 mg/kg), bismuth subsalicylate, or their combination affected mucus gel thickness or pHi homeostasis. In separate experiments, indomethacin (60 mg/kg) significantly increased gastric mucus bismuth concentration in rats given bismuth subsalicylate.. Bismuth accumulation in the gastric mucus during the evolution of mucosal injury may play an important role in the gastroprotective effect of bismuth subsalicylate against indomethacin injury.

Topics: Animals; Bismuth; Blood Flow Velocity; Gastric Acid; Gastric Mucosa; Hydrogen-Ion Concentration; Indomethacin; Male; Organometallic Compounds; Rats; Rats, Sprague-Dawley; Salicylates

This study had three goals: (1) Identify patients with Helicobacter pylori, treat their disease, monitor their progress, and determine that they are no longer infected. (2) Realize a cost savings for our health clinic. (3) Improve patient quality of life. These three goals have been met.

Topics: Amoxicillin; Bismuth; Cost Savings; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metronidazole; Military Personnel; Organometallic Compounds; Peptic Ulcer; Salicylates; Tetracycline; United States; Utah

Topics: Adult; Bismuth; Humans; Male; Organometallic Compounds; Salicylates; Skin

Oxygen free radicals (OFR) are implicated in the pathogenesis of stress, chemically induced gastric lesions, and gastrointestinal injury. The concentration-dependent scavenging abilities of bismuth subsalicylate (SBS), colloidal bismuth subcitrate (CBS), and selected OFR scavengers, including superoxide dismutase (SOD), catalase, mannitol, and allopurinol were examined against biochemically or chemically generated superoxide anion, hydroxyl radical, and hypochlorite radical plus hypochlorous acid based on a chemiluminescence assay. Furthermore, both gastric (GM) and intestinal mucosa (IM) were individually exposed in vitro to these free radical generating systems, and the concentration-dependent protective abilities of SBS and CBS against lipid peroxidation (LP) were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with the necrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol, and aspirin (200 mg/kg). The extent of tissue injury in the GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity. Dose- and time-dependent in vivo protective abilities of CBS (100 mg/kg) and SBS (15 mg/kg) were also assessed. Following incubations with superoxide anion and hydroxyl radical generating systems in the presence of 125 mg SBS/liter, approximately 47% and 61% inhibitions were observed in the chemiluminescence response, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS and CBS exerted similar abilities towards hypochlorite radical plus hypochlorous acid. Approx. 3.1- and 3.7-fold increases in LP were observed in the GM and IM of rats following oral administration of 0.6 M HCl. Pretreatment of the rats with SBS and CBS decreased 0.6 M HCl-induced LP in the GM by approx. 39% and 27%, respectively, with similar decreases in LP in the IM. SBS exhibited better protective abilities towards 0.6 M HCl and 0.2 m NaOH-induced GM and IM injury as compared to CBS. SBS and CBS provided similar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protective ability towards aspirin-induced gastric injury. The results demonstrate that both SBS and CBS can scavenge reactive oxygen species and prevent tissue damage produced by OFR.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Female; Gastric Mucosa; Intestinal Mucosa; Lipid Peroxidation; Luminescent Measurements; Organometallic Compounds; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Salicylates

The sanctuary site where Helicobacter pylori evades antimicrobial therapy is unknown, but considerable data exist about an intracellular location for H pylori. Ten H pylori-infected volunteers received standard triple antimicrobial therapy for 2 weeks. Gastric mucosal biopsy specimens were obtained with jumbo forceps on therapy days 0, 3, 14, and 42. Hematoxylin-eosin staining was used for classification of gastritis and the Genta stain for the visualization of H pylori. Immunohistochemical staining was used to detect HLA-DR antigens, human heat shock protein (HSP60), and the bacterial HSP60 antigen. Bacterial HSP60 was expressed on the mucosal surface and within epithelial cells. No such expression of human HSP60 was found, which supports a bacterial origin for the intracellular HSP60. Coexpression of bacterial HSP60 and HLA-DR was always observed, indicating an ongoing local immune response. Infection was cleared on day 14, but when examined 4 weeks after completion of therapy, Genta staining indicated that only five volunteers remained free of H pylori. However, results of immunohistochemical staining were negative at this time for only two volunteers. Disappearance of intracellular expression of bacterial HSP60 remained after therapy and correlated with the intensity of chronic inflammatory cell infiltration. These data are consistent with the intracellular localization of H pylori having a role in inflammation and as a protective strategy against extracellular antibacterial activity.

Topics: Adult; Antacids; Anti-Bacterial Agents; Antibodies, Bacterial; Antibodies, Monoclonal; Antitrichomonal Agents; Bismuth; Chaperonin 60; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epithelium; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; HLA-DR Antigens; Humans; Immunohistochemistry; Male; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Tetracycline; Time Factors

Three cheetahs (Acinonyx jubatus) had a clinical history of chronic spiral bacteria-associated gastritis and three cheetahs had no clinical history of gastritis. Gastric biopsies were obtained from all six cheetahs prior to treatment for gastritis and 3 wk and 1 yr posttreatment. The cheetahs were treated with tetracycline hydrochloride 500 mg p.o. q.i.d., metronidazole 250 mg p.o. q.i.d., and bismuth subsalicylate 300 mg p.o. q.i.d. Each drug was administered concurrently for 7 days. Following this treatment, each cheetah was maintained on 300 mg bismuth subsalicylate p.o. s.i.d. for 1 yr. The three cheetahs with a history of gastritis were culture positive for Helicobacter acinonyx and remained positive during the entire study. The three cheetahs with no clinical history of gastritis were culture negative for H. acinonyx, but gastric biopsies revealed Gastrospirillum-like bacteria (tentatively named Helicobacter heilmannii) pretreatment. Gastric biopsies were negative for H. heilmannii on subsequent examinations. Although the treatment did not eradicate H. acinonyx, it did provide symptomatic relief from the vomiting, anorexia, and weight loss associated with clinical gastritis. The use of endoscopically guided gastric mucosal biopsies for urease testing and histopathologic examination of Warthin-Starry-stained sections is a sensitive and specific method of diagnosing spiral bacteria-associated gastritis. Treatment of spiral bacteria-associated gastritis in cheetahs should include the rational use of antibiotics (tetracycline or amoxicillin and metronidazole), bismuth compounds, and omeprazole and evaluation of husbandry methods to reduce stress.

Topics: Acinonyx; Animals; Anti-Bacterial Agents; Antitrichomonal Agents; Biopsy; Bismuth; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gastric Mucosa; Gastritis; Gram-Negative Bacterial Infections; Helicobacter; Helicobacter Infections; Lymphocytes; Male; Metronidazole; Organometallic Compounds; Prospective Studies; Salicylates; Sensitivity and Specificity; Tetracycline; Time Factors

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Clarithromycin; Duodenal Ulcer; Esophagitis, Peptic; Female; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Omeprazole; Organometallic Compounds; Penicillins; Prospective Studies; Risk Factors; Salicylates; Sex Factors; Weight Gain

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Recurrence; Salicylates; Stomach Ulcer

Topics: Bismuth; Colon; HIV Infections; Humans; Male; Middle Aged; Organometallic Compounds; Pain; Radiography; Salicylates; Self Medication

Cure of H. pylori infection in peptic ulcer patients significantly reduces the risk of ulcer recurrence. Since data on the rate of H. pylori reinfection in patients undergoing successful anti-H. pylori therapy are sparse, this study was conducted with the aim of determining the H. pylori reinfection rate in peptic ulcer patients receiving antibacterial treatment to heal their ulcer and cure H. pylori infection.. A total of 217 patients with H. pylori-associated duodenal or gastric ulcer were followed up after treatment with various antibacterial regimens resulting in histologically documented cure of H. pylori infection. Endoscopic and histological examinations were performed 4 weeks after completion of treatment and after 1, 2 and 5 years, or whenever dyspeptic symptoms occurred. To assess the H. pylori status two antral and two corpus biopsies were obtained for histological examination.. Out of 217 patients with initially cured H. pylori infection 175 were available for endoscopic follow-up. At the time of analysis, 44 patients were re-examined after 1 year, 113 patients after 2 years and 18 patients after 5 years, giving a total of 360 patient years of follow-up. The mean duration of follow-up was 24.7 months. H. pylori reinfection was confirmed histologically in eight patients, three of whom becoming H. pylori-positive again within the first year of follow-up. Six of the eight patients with H. pylori reinfection also suffered an ulcer relapse. Eight cases of reinfection in 360 patient years represents an overall reinfection rate of 2.2%. Within the first 2 years of follow-up the reinfection rate was 0.8% per year.. Our data suggest that H. pylori reinfection is rare in peptic ulcer patients receiving successful anti-H. pylori therapy. H. pylori reinfection frequently coincides with ulcer recurrence. Cure of H. pylori infection results in cure of peptic ulcer disease, provided H. pylori reinfection does not occur.

Topics: Amoxicillin; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Organometallic Compounds; Penicillins; Recurrence; Salicylates; Stomach Ulcer; Time Factors; Tinidazole

Topics: Amoxicillin; Anti-Bacterial Agents; Antitrichomonal Agents; Bismuth; Cost of Illness; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Organometallic Compounds; Penicillins; Peptic Ulcer; Pilot Projects; Salicylates; Tetracycline

Recrudescence or reinfection may occur after eradication of Helicobacter pylori in humans.. We used the ferret Helicobacter mustelae model to investigate the effect of prior infection and eradication on reinfection by experimental and natural routes. Two groups of ferrets with naturally acquired H. mustelae infection were treated with an eradication protocol using amoxicillin, metronidazole, and bismuth subsalicylate. The ferrets were monitored for recrudescence by repeated cultures of endoscopic gastric mucosal biopsies. The ferrets were challenged at 17 months (group I) and 6 months (group II) after eradication with a strain of H. mustelae having a distinctive restriction endonuclease analysis pattern. The eradication protocol was repeated to eliminate the infection produced by experimental challenge. The ferrets were then cohoused intermittently with naturally infected ferrets.. The original H. mustelae infection was successfully eliminated by the eradication protocol. No recrudescence was observed in group I for 12 months nor for 3 months in group II after eradication. All ferrets became persistently reinfected with the challenge strain. The infection from the challenge strain was eradicated successfully. No ferrets in group I and all ferrets in group II became infected through cohousing.. These results suggest that though prior infection with H. mustelae may confer some protection against reinfection, such protection is not universal in all circumstances; that susceptibility to reinfection by contact with infected animals varies between individuals; and that age may be a factor in this individual variability. These results are applicable to studies of reinfection after eradication of H. pylori in humans.

Topics: Amoxicillin; Animals; Antacids; Bacterial Proteins; Biopsy; Bismuth; DNA, Bacterial; Drug Therapy, Combination; Ferrets; Gastric Mucosa; Gastritis; Gastroscopy; Helicobacter; Helicobacter Infections; Metronidazole; Organometallic Compounds; Recurrence; Salicylates; Time Factors; Urease

Numerous clinical trials evaluating the efficacy of various antimicrobial compounds against Helicobacter pylori infection have been performed in humans. A convenient animal model for Helicobacter infection would facilitate the evaluation of novel therapies. These experiments were performed to evaluate the use of ferrets as a model of Helicobacter infection.. Ferrets were infected experimentally with Helicobacter mustelae and subsequently treated with bismuth subsalicylate (BSS) triple therapy (BSS, metronidazole, and amoxicillin), or left untreated. The status of infection and serology was assessed during treatment and for 8 weeks posttreatment. Seven ferrets successfully treated with triple therapy were challenged with H. mustelae and monitored for infection for an additional 5 weeks.. Infection of ferrets by H. mustelae was accompanied by gastritis and a specific antibody response. Treatment of H. mustelae-infected ferrets with BSS suppressed bacterial growth in four of nine animals but did not eradicate infection. Triple therapy eradicated infection in all nine ferrets with a reduction in gastric inflammation. No relapse of infection occurred up to 8 weeks posttherapy. Challenge with H. mustelae of ferrets successfully treated with triple therapy resulted in a 100% rate of reinfection.. H. mustelae infection can be eliminated by triple therapy, but this does not result in protective immunity against reinfection by H. mustelae. This model, using a strain of Helicobacter indigenous to the host, may be useful for assessing therapeutic efficacy of novel therapies for the treatment of human infection by H. pylori.

Topics: Amoxicillin; Animals; Antacids; Antibodies, Bacterial; Bismuth; Drug Therapy, Combination; Female; Ferrets; Gastritis; Helicobacter; Helicobacter Infections; Male; Metronidazole; Organometallic Compounds; Salicylates; Specific Pathogen-Free Organisms

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Organometallic Compounds; Penicillins; Peptic Ulcer; Ranitidine; Salicylates; Tetracycline

Topics: Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Eczema; Gastroenteritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Recurrence; Salicylates; Tetracycline

To determine the role of Helicobacter pylori infection in children with recurrent abdominal pain and the usefulness of serologic tests in screening H pylori infection and monitoring treatment of H pylori-associated gastritis.. During a 3 year period, we investigated the presence of serum immunoglobulin G (IgG) antibody to H pylori in 456 children using the high-molecular-weight cell-associated protein H pylori enzyme immunoassay kit. Among the 456 children studied, 218 (age range, 3 to 18 years; mean age, 9.5 years) had symptoms of recurrent abdominal pain (RAP syndrome) with or without vomiting, and the remaining 238 (age range, 3 to 18 years; mean age, 9.8 years) had no RAP (non-RAP syndrome). We performed upper gastrointestinal endoscopy on 111 consecutive children of the 218 with RAP syndrome and obtained mucosal biopsies for culture, histologic analysis, CLO test (Delta West, Perth, Australia), and H pylori detection by polymerase chain reaction.. Thirty-eight (17.4%) of 218 children in the RAP group and 25 (10.5%) of 238 children in the non-RAP group were seropositive for H pylori. Of the 111 children endoscoped, 95 were found to be negative, and 12 were positive by all five assays. Specimens from 2 children were negative by culture and the CLO test but positive by the other three assays. Specimens from 1 child were negative by histologic analysis but positive by all other tests. The remaining child was positive for anti-H pylori IgG but negative by all of the other four assays. Upper gastrointestinal endoscopy detected 14 children with peptic ulcer disease (9 duodenal ulcer and 5 gastric ulcer) and 12 with antral nodular gastritis. Only 4 of the 14 diagnosed with peptic ulcer were H pylori positive by all five assays, whereas all 12 children with antral nodular gastritis were H pylori positive. Nine of the 12 H pylori-positive children were treated with a combination of bismuth subsalicylate, amoxicillin, and metronidazole for 2 weeks. Sera obtained at 2, 4, and 6 months after treatment from all 9 children showed a decrease in anti-H pylori IgG titer. Three H pylori-infected children who did not receive any treatment served as control children, and their IgG levels remained elevated or increased over time.. The results from our study indicate that screening for the serum IgG antibody to H pylori is a practical method for diagnosing H pylori infection in children, and that serial measurements of the H pylori IgG antibody are useful for monitoring treatment of H pylori because of its high sensitivity and ease of performance. Only 4 of the 14 children diagnosed with peptic ulcer disease were confirmed to be infected with H pylori, whereas all 12 children with antral nodular gastritis were found to be infected by H pylori. These observations suggest that H pylori infection is more frequently associated with gastritis than with peptic ulcer disease in children, and that H pylori gastritis is a cause of RAP syndrome in children.

Topics: Abdominal Pain; Adolescent; Amoxicillin; Antibodies, Bacterial; Bismuth; Child; Child, Preschool; Duodenal Ulcer; Endoscopy, Gastrointestinal; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Metronidazole; Organometallic Compounds; Polymerase Chain Reaction; Recurrence; Salicylates; Stomach Ulcer

Colonic mucin is heavily sulphated and it has been shown that enzymatic desulphation by faecal bacterial sulphatases greatly increases its susceptibility to degradation by faecal glycosidases. A possible role for faecal mucin sulphatase in the pathogenesis of inflammatory bowel disease has therefore been explored. Faecal mucin sulphatase activity assayed using 35S mucin as substrate was increased in ulcerative colitis (median 80.2 units/g pellet weight (range 6.9-1063; 95% confidence intervals (CI): 45.2 to 293.8, n = 22) compared with 11.3 units/g (range 3.0-53.5; 95% CI: 8.7 to 29.8, n = 17) in healthy controls (p < 0.01), where one unit released 1000 dpm free sulphate/hour from 35S mucin (1680 dpm/microgram). Patients with active ulcerative colitis had higher sulphatase activity (median 146; 95% CI: 98 to 253 units/g, n = 10) than those with inactive ulcerative colitis (median 42.2; CI: 22.5 to 81.6 units/g, n = 12) (p < 0.05). Longitudinal studies in patients with ulcerative colitis show fluctuations of faecal mucin sulphatase activity corresponding to clinical disease activity in six of seven patients. Faecal mucin sulphatase activity was not significantly increased in Crohn's disease (median 36.6, range 5.7-106.6; 95% CI: 22.9 to 65.3 units/g, n = 14). The bismuth salts, bismuth subcitrate and bismuth subsalicylate were found to inhibit faecal mucin sulphatase activity at concentrations achievable therapeutically. The increased faecal mucin sulphatase activity in ulcerative colitis could be the result of greater intraluminal substrate (mucin) availability leading to bacterial enzyme induction, but would probably result in more rapid degradation of secreted mucin and represents a potential target for treatment.

Topics: Adult; Aged; alpha-Glucosidases; Bismuth; Colitis, Ulcerative; Crohn Disease; Feces; Female; Humans; Longitudinal Studies; Male; Middle Aged; Organometallic Compounds; Salicylates; Sulfatases

While the antimicrobial and antisecretory effects of bismuth salts are well documented, little is known regarding their effects on immune responses to enterotoxins such as that of V. cholerae or to orally administered vaccine antigens. To evaluate the effects of Pepto Bismol (PB) on the induction of systemic and mucosal immune responses to cholera toxin (CT), C57BL/6 mice were orally administered 10 micrograms CT and PB, or mice were pretreated with PB 30 min prior to CT administration. When co-administered with CT, PB attenuated serum IgG1, IgG2a, IgG2b and IgG3 anti-CT responses in a dose-dependent manner and also reduced levels of circulating anti-CT IgA and total serum IgE. Similarly, anti-CT intestinal IgA responses were also decreased. However, when administered 30 min prior to CT, PB had little to no effect on serum or intestinal anti-CT immunoglobulin responses. Administration of bismuth subsalicylate (BSS), the active component of PB, or sodium salicylate did not reduce immune responses to CT, suggesting that the combination of BSS plus other constituents contained within PB contributed to the decreased immune response to CT. Moreover, bismuth subgallate alone inhibited antibody responses to CT. Our data are consistent with the hypothesis that, when administered orally with CT, PB and bismuth subgallate create a physical barrier to antigen uptake.

Topics: Administration, Oral; Animals; Antitoxins; Bismuth; Cholera Toxin; Enzyme-Linked Immunosorbent Assay; Feces; Female; Immunity, Mucosal; Immunization; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Mice; Mice, Inbred C57BL; Organometallic Compounds; Salicylates; Sodium Salicylate; Time Factors

Mucus and bicarbonate secretions have been widely implicated as an important pre-epithelial protective barrier against autodigestion of the gastric mucosa by acid and pepsin. Evidence from several independent studies shows there is a continuous layer of resilient viscoelastic mucus gel adherent to the surface of the gastroduodenal mucosa. The median thickness of the adherent gastric mucus layer in humans is 180 microns, range 50-450 microns. The epithelial bicarbonate secretion permeates the unstirred matrix of mucus gel neutralizing luminal acid and establishing a pH gradient within the gel. In the duodenum, evidence supports the mucus bicarbonate barrier as a major protective mechanism against acid aggression. The adherent mucus gel, by acting as an effective 'permeability' barrier to pepsin, protects the underlying sensitive mucosa from digestion. However, pepsin slowly digests mucus gel at its luminal surface to produce soluble degraded mucin. In a rat gastric damage model in vivo, pepsin in excess digests the gastric mucus barrier sufficiently rapidly to outweigh new mucus secretion and lead to breaching of the mucus barrier with the formation of small punctate ulcers in the epithelium accompanied by mucosal haemorrhage. The mucus secretagogue 16,16 dimethyl prostaglandin E2 and the muco-adhesive carbopol-polyacrylate both fully protected the mucosa against pepsin damage by enhancing the protective properties of the mucus barrier. Sucralfate and bismuth subsalicylate were partially effective in protection against pepsin damage but this protection was mainly mediated at the level of the mucosa. In peptic ulcer disease, there is increased mucolytic (mucus degrading) activity in gastric juice and this is associated with an impaired mucin polymeric structure and a weaker mucus barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 16,16-Dimethylprostaglandin E2; Acrylic Resins; Animals; Bismuth; Duodenum; Gastric Mucosa; Intestinal Mucosa; Male; Mucus; Organometallic Compounds; Pepsin A; Peptic Ulcer; Rats; Rats, Wistar; Salicylates; Sucralfate

Fifty patients with relapsing or complicated Helicobacter pylori positive duodenal (n = 41) or gastric ulcer disease (n = 9) and failure of a combined treatment with omeprazole plus amoxycillin to eradicate H. pylori infection were re-treated with either oral triple therapy (bismuth subsalicylate, metronidazole, tetracycline) plus ranitidine [group I: n = 22] or high-dose omeprazole (40 mg b.d. to t.d.s.) plus amoxycillin (1 g t.d.s.) [group II: n = 28].. Patients of group I and II had similar demographic and clinical characteristics. The overall proportion of eradication of H. pylori infection was 81.8% in group I and 78.6% in group II (P = N.S.) as judged from negative bacterial findings by means of an urease test, specific culture and histology after modified Giemsa stain. Ulcer healing was observed in all patients after a maximum duration of 10 weeks. Ten patients on triple therapy and only one patient on omeprazole plus amoxycillin (45.5% vs. 3.6%; P < 0.001) complained of side effects without necessity of discontinuation of the study medication in either group. Twenty patients (group I: n = 10; group II: n = 10) with relapsing duodenal ulcer disease and successful cure were prospectively followed for one year without any evidence of ulcer relapse or H. pylori re-infection.. Oral triple therapy plus ranitidine or high-dose omeprazole plus amoxycillin remain highly effective in eradicating H. pylori infection in patients with peptic ulcer disease and treatment failure of omeprazole/amoxycillin, but the omeprazole enhanced antibiotic monotherapy seems to be superior with regard to side effects. Thus, high-dose omeprazole/amoxycillin is recommended as the treatment of first choice in these selected patients. Triple therapy should be reserved for patients intolerant of amoxycillin.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Amoxicillin; Bismuth; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Peptic Ulcer; Prospective Studies; Ranitidine; Recurrence; Salicylates; Tetracycline; Treatment Failure; Treatment Outcome

Topics: Ataxia; Bismuth; Confusion; Delirium; Dyspepsia; Gait; Humans; Male; Memory Disorders; Middle Aged; Organometallic Compounds; Remission, Spontaneous; Salicylates; Tremor

Metronidazole resistance has become an increasing problem that has limited the usefulness of the original triple therapy. Our objective was to evaluate clarithromycin, a new macrolide compound active against Helicobacter pylori.. We evaluated a new clarithromycin triple therapy for H. pylori infection consisting of the combination of clarithromycin (500 mg t.i.d.), tetracycline (500 mg q.i.d.), and bismuth subsalicylate tablets (2 q.i.d.) for 14 days. Patients with ulcer also received concomitant ranitidine, 300 mg after the evening meal, for 6 wk.. Thirty men with documented H. pylori infection were studied; 29 had peptic ulcer disease. Seven had previously failed antimicrobial therapy, including three with metronidazole-based triple therapy. H. pylori status was determined by histology. H. pylori status and ulcer status were evaluated 4 wk after the end of antimicrobial therapy. The ulcer was healed in 90%. The H. pylori infection was cured in 93%, including all three patients who previously failed metronidazole-based triple therapy.. We conclude that the combination of clarithromycin, tetracycline, and bismuth is an effective new therapy for treatment of H. pylori infection.

Topics: Adult; Aged; Bismuth; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Peptic Ulcer; Ranitidine; Salicylates; Tetracycline; Time Factors

To study the relationship between Helicobacter pylori infection, gastric inflammatory scores, and fasting gastrin and pepsinogen A and C concentrations, and to evaluate the effect of treatment on these parameters.. Gastrin and pepsinogen A and C concentrations were measured in 36 patients with gastritis, 10 gastric ulcer patients, 12 duodenal ulcer patients, and in 15 subjects with normal gastric mucosa, by standard radioimmunoassay techniques. Fifteen patients with H. pylori infection underwent triple therapy (bismuth subsalicylate, amoxicillin, metronidazole) and were reassessed 1 month later.. Fasting gastrin and pepsinogen A and C concentrations were significantly higher in H. pylori-positive gastritis and peptic ulcer patients than in subjects with normal mucosa and in patients with H. pylori-negative gastritis. There was a significant correlation between inflammatory scores and serum gastrin (r = 0.45, p < 0.0001), and pepsinogen A (r = 0.33, p < 0.006) and pepsinogen C (r = 0.55, p < 0.0001) concentrations. Neither sex nor age affected basal gastrin and pepsinogen concentrations. Eradication of H. pylori infection was successful in 12 patients and resulted in a significant fall in serum gastrin and in pepsinogen A and C concentrations, and in a concomitant improvement of the inflammatory scores. Serum peptide levels and gastritis scores were unchanged in those patients in whom H. pylori infection persisted.. These findings suggest that hypergastrinemia and hyperpepsinogenemia are secondary to H. pylori infection and are related to mucosal inflammation.

Topics: Amoxicillin; Bismuth; Drug Therapy, Combination; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Pepsinogens; Peptic Ulcer; Salicylates

We have recently shown that colloidal bismuth subcitrate inhibits cytosolic alcohol dehydrogenase of Helicobacter pylori as well as acetaldehyde production from excess ethanol. We now extend our studies to bismuth subsalicylate and nitecapone, a novel antiulcer agent.. Cytosol of H. pylori was incubated with 0.1% or 1% ethanol in the presence of different drug concentrations for 2 h, whereafter acetaldehyde formed was analyzed by head space gas chromatography. In addition, we incubated a culture solution containing intact bacteria with the drugs at 1% ethanol.. Bismuth subsalicylate and nitecapone inhibit acetaldehyde formation from 0.1% ethanol by H. pylori cytosol at drug concentrations theoretically achievable in the stomach after intake of therapeutic doses of these drugs. Furthermore, colloidal bismuth subcitrate, bismuth subsalicylate, and nitecapone also inhibit acetaldehyde production by intact H. pylori, although rather high drug concentrations are required for this to occur.. Inhibition of H. pylori acetaldehyde formation may be one of the mechanisms by which bismuth and nitecapone exert their effect in the treatment of H. pylori-related disorders.

Topics: Acetaldehyde; Anti-Ulcer Agents; Bismuth; Catechols; Colloids; Depression, Chemical; Ethanol; Helicobacter pylori; Organometallic Compounds; Pentanones; Salicylates

Lymphocytic gastritis (LG) is a recently described histological entity characterized by increased lymphocytes in the superficial gastric epithelium and foveolae. It includes a subgroup of patients with giant gastric folds and, often, a protein-losing state, a condition termed hypertrophic lymphocytic gastritis (HLG). Despite close endoscopic and clinical similarities to classical Menetrier's disease, the histopathological features of these two diseases are sufficiently distinct that they are regarded as separate entities. The etiology and pathogenesis of HLG are unknown, and the possible etiological role of Helicobacter pylori in particular is controversial. For this reason we report the case of a 48-yr-old female with HLG, hypoproteinemia, and H. pylori infection whose disease resolved clinically, endoscopically, and pathologically with therapeutic eradication of the H. pylori. H. pylori infection may be a treatable cause of at least some cases of HLG and should therefore be carefully sought in any patient with this condition.

Topics: Amoxicillin; Bismuth; Drug Therapy, Combination; Female; Gastric Mucosa; Gastritis, Hypertrophic; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Protein-Losing Enteropathies; Salicylates

Topics: Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Peptic Ulcer; Salicylates

Topics: Aged; Bismuth; Female; Humans; Organometallic Compounds; Radiography, Abdominal; Salicylates

The objective of the present work was to determine the effect of treating Helicobacter pylori infection on the recurrence of peptic ulcer bleeding. We prospectively followed 66 out of 70 consecutive H. pylori-positive (histology and/or culture) patients with conservatively and endoscopically managed peptic ulcer bleeding (duodenal ulcer; n = 39, gastric ulcer: n = 25, gastroduodenal double ulcer: n = 2) for a median period of 17 months (range 6-33 months). Patients were treated in seven different clinical protocols, each of which included the attempt to eradicate H. pylori infection. Patients with (n = 42) and without (n = 24) bacterial eradication had similar demographic and clinical characteristics. Eradication of H. pylori was associated with a statistically significant reduction of ulcer recurrences (2.4 vs. 62.5%; p < 0.001) and bleeding relapses (0 vs. 37.5%; p = 0.01). We conclude that H. pylori eradication markedly changes the natural history in patients with complicated duodenal and gastric ulcer disease. Thus, treatment aimed at bacterial eradication should be considered in all patients with conservatively managed bleeding from H. pylori-positive ulcers.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Peptic Ulcer; Peptic Ulcer Hemorrhage; Prospective Studies; Ranitidine; Recurrence; Salicylates; Stomach Ulcer

To investigate the change of vitamin C concentration (ascorbic and dehydroascorbic acid) in gastric juice after anti-Helicobacter pylori treatment, and to relate any observed change to gastric pH, inflammatory compromise of the gastric mucosa, plasma vitamin C concentration, and smoking habits.. Plasma and gastric juice vitamin C, fasting gastric juice pH, gastric histology, and smoking status were studied in 70 patients with H. pylori-associated gastritis before and after therapy.. Gastric juice ascorbic acid increased significantly after H. pylori clearance. For the most part, this change was confined to patients who experienced reduction of gastric pH. It was also related to improvement of the compromise of the gastric epithelium, reduction of the proportion of vitamin C composed by dehydroascorbic acid, and increase of the gastric juice/plasma vitamin C concentration gradient. Smokers had lower vitamin C concentrations in plasma and gastric juice before and after H. pylori clearance than nonsmokers.. The findings are consistent with a causal association between H. pylori infection and low ascorbic acid levels in gastric juice, and support two mechanisms for this association: increased oxidation and a decreased secretion of ascorbic acid.

Topics: Amoxicillin; Ascorbic Acid; Bismuth; Female; Gastric Juice; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Nitrofurantoin; Organometallic Compounds; Salicylates; Smoking

Topics: Amoxicillin; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Organometallic Compounds; Ranitidine; Salicylates; Tetracycline

Topics: Aged; Bismuth; Electroencephalography; Female; Humans; Magnetic Resonance Imaging; Nervous System Diseases; Organometallic Compounds; Salicylates; Substance-Related Disorders

Helicobacter pylori infection is associated with exaggerated gastrin release. We investigated whether this abnormality was due to the bacteria or the immune response. Fasting and meal-stimulated 'total' and amidated gastrin were measured in 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after completion of therapy. The exaggerated meal-stimulated gastrin concentration remained unchanged after 2 days of therapy, although the polymorphonuclear cell infiltrate and H. pylori bacteria were no longer evident. The expected fall in gastrin concentration after 14 days of therapy was associated with a reduction in the density of mucosal mononuclear cells, suggesting exaggerated gastrin release was related to chronic inflammation or to H. pylori or its products. The effect of H. pylori on normal progastrin processing was also assessed; 2 control groups were included: 10 H. pylori-uninfected volunteers and 13 patients with H. pylori peptic ulcers. There was a significant difference in the proportion of circulating gastrins that were biologically active amidated gastrins between ulcer patients and uninfected controls (56.7 +/- 4% versus 33.8 +/- 4%, p < 0.001). The proportion of amidated to total gastrins did not increase after successful eradication.

Topics: Adult; Bismuth; Female; Food; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Organometallic Compounds; Peptic Ulcer; Protein Precursors; Protein Processing, Post-Translational; Salicylates; Tetracycline

We have investigated the effect of therapy for Helicobacter pylori gastritis on serum concentrations of pepsinogen I and II in 43 patients. In the 22 patients in whom therapy resulted in dramatic decrease in gastritis scores and in clearance of the bacteria, there was a highly significant (P = 0.0001) fall in mean serum pepsinogen II from 13.3 +/- 0.8 to 7.9 +/- 0.7 micrograms/liter, and a less pronounced fall in pepsinogen I from 89.0 +/- 5.9 to 78.5 +/- 0.4 micrograms/liter (P = 0.01). These changes resulted in a significant (P = 0.01) increase in the pepsinogen I/II ratio. In contrast, nonsignificant declines of 3.5% and 11.6% were observed in mean pepsinogen I and II levels in the 21 patients whose gastritis failed to resolve histologically and whose infection did not clear. These findings suggest that serum pepsinogen levels, especially pepsinogen II, are a new tool that may be found to be clinically useful in evaluation of treatment outcome in patients with H. pylori-associated gastritis.

Topics: Adult; Biopsy; Bismuth; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Nitrofurantoin; Organometallic Compounds; Pepsinogens; Salicylates

Topics: Bismuth; Child; Diarrhea, Infantile; Fluid Therapy; Humans; Infant; Organometallic Compounds; Salicylates

Topics: Bismuth; Child; Diarrhea, Infantile; Fluid Therapy; Humans; Infant; Organometallic Compounds; Salicylates

Topics: Aspirin; Bismuth; Child; Humans; Organometallic Compounds; Salicylates; Stomach Diseases

In a 7-year period, 33 children had endoscopically documented duodenal ulcer disease. Of the 33 children, 29 had Helicobacter pylori antral gastritis. All children with H. pylori-associated duodenal ulcer disease were treated with antibiotics but no H2-receptor blocking agents. For the first 3 years of the study, initial treatment was with bismuth subsalicylate or amoxicillin for 6 weeks. For the latter 4 years, therapy with both bismuth subsalicylate and amoxicillin for 6 weeks was used initially; those in whom treatment failed received bismuth subsalicylate and amoxicillin for 6 weeks, and metronidazole for 4 weeks. Follow-up with endoscopic biopsies was performed immediately after each treatment course and at a mean of 6.5 months after clearance of H. pylori from antral biopsy specimens. Data for noncompliant patients and those receiving nonsteroidal antiinflammatory drugs were analyzed separately. For compliant patients, the rates of H. pylori clearance from antral biopsy specimens immediately after each treatment were as follows: bismuth subsalicylate, 6 of 12 children; amoxicillin, 1 of 5 children; double therapy, 9 of 9 children; and triple therapy, 3 of 3 children. At long-term follow-up, the number of children with no H. pylori in antral biopsy specimens were as follows: monotherapy, 1 of 5; double therapy, 4 of 4; and triple therapy, 3 of 3. Of the noncompliant patients, only 1 of 5 had H. pylori eradication with combination therapy and none had H. pylori eradication with monotherapy. Duodenal ulcer disease had healed in all children with H. pylori-negative antral biopsy specimens at follow-up; duodenal ulcers recurred in all children with persistent or recurrent H. pylori infection. We conclude that therapy with two drugs for 6 weeks is the treatment of choice for endoscopically proved duodenal ulcer and histologically proved H. pylori antral gastritis, and that poor patient compliance reduces the rate of success. Our data strongly support a causal relationship between H. pylori and duodenal ulcer disease.

Topics: Adolescent; Amoxicillin; Biopsy; Bismuth; Child; Child, Preschool; Drug Therapy, Combination; Duodenal Ulcer; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Organometallic Compounds; Pyloric Antrum; Recurrence; Salicylates; Time Factors; Treatment Outcome

25 patients with Helicobacter pylori-associated active duodenal ulcer disease (bleeding: n = 5, penetrating: n = 1, stenosis of the bulb: n = 4, frequent ulcer relapse: n = 18) were treated with 3 x 600 mg bismuth subsalicylate (BSS), 3 x 400 mg metronidazole and 3 x 500 mg tetracycline in addition to 300 mg ranitidine. 23 out of 25 patients (92%) proved to be Helicobacter pylori-negative four weeks after cessation of study medication as judged from negative urease test, specific culture and histology after modified Giemsa staining. 24/25 ulcers (96%) had healed after six weeks. In one patient on NSAIDs a small duodenal ulcer was detected on the final endoscopic examination despite successful Helicobacter pylori eradication. Twelve out of 25 (48%) patients complained side effects that did not lead to discontinuation of therapy. In conclusion, oral triple therapy with BSS, metronidazole and tetracycline is highly effective in Helicobacter pylori eradication, but there was a rather high rate of more or less serious side effects, diminishing the attractiveness of this therapeutic regimen.

Topics: Administration, Oral; Adult; Aged; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Prospective Studies; Ranitidine; Salicylates; Tetracycline

To establish the rate of Helicobacter pylori recurrence after a standard triple-therapy regimen (bismuth subsalicylate, tetracycline, metronidazole) and determine which clinical factors affect reinfection, we prospectively followed 118 patients after successful H. pylori eradication. Elimination of H. pylori was confirmed by repeat endoscopy and urea breath test 4 wk after completion of therapy. Serial [13C]urea breath tests were performed at 3-month intervals; antral biopsies were used to verify reinfection. Recurrence of H. pylori infection occurred in 4/118 (3.4%) patients. Three of the four relapses occurred in the 1st yr after treatment. Gender, age, ethnic group, alcohol consumption, cigarette use, and gastrointestinal diagnosis do not predict H. pylori recurrence. We conclude that the rate of recurrence after successful H. pylori eradication is low, and that when reinfection takes place, it occurs most commonly within the 1st yr after treatment.

Topics: Bismuth; Drug Therapy, Combination; Female; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Recurrence; Salicylates; Tetracycline

Topics: Bismuth; Diarrhea, Infantile; Fluid Therapy; Humans; Infant; Organometallic Compounds; Salicylates

The use of an ammonia electrode to quantify ammonia liberated by urease from Helicobacter pylori was assessed in an in vitro study. It was found to be highly sensitive (down to 0.7 ppm NH3) and highly reproducible (coefficient of variation 6.0%). Inhibition of urease by bismuth subsalicylate was evaluated as urease testing is often used to assess clearance of H. pylori in patients treated with bismuth. Concentrations of bismuth subsalicylate up to 5 mg/ml had no inhibitory effect but bismuth subsalicylate at 50 mg/ml resulted in 21% inhibition of the urease activity of an ultrasonicated H. pylori suspension. As a preliminary study, the ammonia electrode was assessed in the endoscopy room in comparison with conventional techniques for H. pylori diagnosis. Antral biopsies from 39 patients attending for routine diagnostic endoscopy were subjected to culture, histology, detection of urease activity with a commercially available slide test (CLO) and with the ammonia electrode to detect ammonia liberated from samples placed in urea solution. 21 patients were positive after 1 h with the ammonia electrode, compared to only 17 with the commercially available slide test. 20 were positive on histology and 19 by culture. All samples positive with the ammonia electrode were either positive by culture or by histology. The ammonia electrode offers a quick, sensitive, quantitative and cheap method for the detection and quantification of H. pylori.

Topics: Ammonia; Bismuth; Electrodes; Female; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; In Vitro Techniques; Male; Middle Aged; Organometallic Compounds; Salicylates; Sensitivity and Specificity; Urease

The influence of salicylate or bismuth salts on antibiotic action against Pseudomonas aeruginosa was assessed in broth cultures. Sodium salicylate (2.5 mM) had no significant effect on the activity of any antibiotic tested. In contrast, bismuth compounds (0.5 mM) produced a significant change in the inhibitory activity of several antibiotics against all strains. Bismuth salts reduced imipenem activity by up to 20-fold, enhanced gentamicin or amikacin activity three to five-fold, and enhanced cefpirome or cefepime activity by as much as 10-fold against antibiotic-sensitive and resistant strains. Bismuth salts had little effect on cefoperazone, ceftazidime, or mezlocillin activity. Combining bismuth salts with aminoglycosides or fourth-generation cephalosporin antibiotics may help to combat the growing problem of resistant Pseudomonas aeruginosa.

Topics: Anti-Bacterial Agents; Bismuth; Drug Interactions; Microbial Sensitivity Tests; Organometallic Compounds; Pseudomonas aeruginosa; Salicylates; Salicylic Acid; Sodium Salicylate

Topics: Bismuth; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Peptic Ulcer; Ranitidine; Recurrence; Salicylates; Tetracycline

Topics: Abdomen; Administration, Oral; Adult; Bismuth; Calcinosis; Diagnosis, Differential; Foreign Bodies; Humans; Male; Organometallic Compounds; Pancreatic Diseases; Radiography; Salicylates

The effects of sublethal concentrations of bismuth salts on bacterial invasion of mammalian cells were investigated. Pepto-Bismol, bismuth subsalicylate, and bismuth oxychloride, produced by interacting bismuth subsalicylate and simulated gastric juice, in suspension at concentrations as low as 1.4 mM significantly interfered with the invasion of RPMI-4788 cells by two different strains of Yersinia enterocolitica. Invasion of the mammalian epithelial cells by other enteric bacteria was also reduced significantly by some of these bismuth salts. Commercially obtained bismuth oxychloride, bismuth sulfide, and sodium salicylate had no affect on invasion by Y. enterocolitica. Exposure of Y. enterocolitica 8081c to Pepto-Bismol for as brief a time as 5 min was sufficient to produce the inhibitory effect. Removal of bismuth bound to bacteria by sodium potassium tartrate did not reverse the inhibition. Electron-dense deposits are observed in Y. enterocolitica 8081c exposed to bismuth subsalicylate, suggesting that interference of invasion may result from bismuth permeation of the bacterial cell wall.

Topics: Bacteria; Bismuth; Colony Count, Microbial; Gastrointestinal Diseases; Humans; Intestinal Mucosa; Organometallic Compounds; Salicylates; Tumor Cells, Cultured

Yersinia enterocolitica 8081c cultures in exponential growth were incubated for 1 h in 0.1% microcrystalline bismuth subsalicylate (BSS) suspensions. Scanning electron microscopy (SEM) revealed microcrystals directly bound to BSS-treated bacteria. Energy dispersive spectroscopy (EDS) X-ray microanalysis of the attached microcrystals confirmed that the crystals were the microcrystalline BSS. X-ray spectra positive for bismuth were also obtained by SEM-EDS X-ray microanalysis of whole bacteria, suggesting metal incorporation into the bacteria in regions absent of bound microcrystals. Transmission electron microscopy of thin sections of embedded preparations of BSS-treated exponential-growth-phase bacteria showed electron-dense deposits in the periphery of the bacteria. Y. enterocolitica cultures that were in stationary phase at the time of incubation with microcrystalline BSS showed no evidence of the electron-dense deposits and EDS spectra were negative for bismuth. Bacteria incubated in the absence of microcrystalline BSS also lacked electron-dense deposits. Scanning transmission electron microscopy used in conjunction with EDS X-ray microanalysis to view and analyze semi-thick sections (250-300 nm) of embedded preparations of BSS-treated bacteria in exponential growth confirmed that the electron-dense deposits at the periphery of the bacteria are the sites of bismuth depositions.

Topics: Bismuth; Crystallization; Electron Probe Microanalysis; Microscopy, Electron, Scanning; Organometallic Compounds; Salicylates; Yersinia enterocolitica

Assessment of intragastric urease activity by the 13C-urea breath test was performed before and after one day of dosing with either De-Noltabs (tripotassium dicitrato bismuthate, one tablet 1 q.d.s.), Pepto-Bismol liquid (bismuth salicylate 30 ml q.d.s.), or Roter tablets (bismuth subnitrate, one tablet q.d.s.) in twelve Helicobacter pylori-positive patient volunteers. There was a significant decrease in the excess of 13CO2 after one day of dosing with each of the three bismuth compounds, but analysis of variance could detect no difference between the effects of the three compounds. Systemic absorption of bismuth following oral dosing with either Pepto-Bismol or Roter is minimal, yet both compounds have a suppressive effect on H. pylori similar to that of De-Noltab. This study suggests that the action of all three bismuth compounds is within the gastric lumen, and that systemic absorption of bismuth is not necessary for activity against H. pylori.

Topics: Adult; Aged; Analysis of Variance; Bismuth; Breath Tests; Carbon Dioxide; Female; Gastric Mucosa; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Salicylates; Urea; Urease

Helicobacter pylori infection has been associated with gastritis, duodenal ulcer, gastric ulcer, and the epidemic form of gastric carcinoma. Eradication of H. pylori infection has proven to be difficult. Recently, combinations of antimicrobial drugs have been shown to eradicate greater than 50% of infections; however, the results have proven variable, and the factors influencing effectiveness of therapy are unclear. In the present study, the effectiveness of a triple therapy for eradication of H. pylori infection was evaluated. Triple therapy consisted of 2 g tetracycline, 750 mg metronidazole, and five or eight tablets of bismuth subsalicylate daily in 93 patients (70 with duodenal ulcer, 17 with gastric ulcer, and 6 with simple H. pylori gastritis). Combinations of a sensitive urea breath test, serology, culture, and histology were used to confirm the presence of infection, eradication, or relapse. Eradication was defined as inability to show H. pylori greater than or equal to 1 month after ending therapy. The overall eradication rate was 87%. The factors evaluated for their effect on predicting eradication included age, gender, type of disease, duration of therapy, amount of bismuth subsalicylate [five or eight Pepto-Bismol tablets daily (Procter & Gamble, Cincinnati, OH)], and compliance with the prescribed medications. Stepwise regression showed that compliance was the most important factor predicting success; the success rate was 96% for patients who took greater than 60% of the prescribed medications and 69% for patients who took less. For those taking greater than 60% of the prescribed therapy, the eradication rates were similar (a) for patients receiving therapy for 14 days or when tetracycline and bismuth subsalicylate were taken for an additional 14 days; (b) for patients with duodenal ulcer, gastric ulcer, and simple H. pylori gastritis; and (c) whether five or eight bismuth subsalicylate tablets were taken. It is concluded that triple therapy is effective for eradication of H. pylori and that future studies need to take compliance into account for comparisons between regimens.

Topics: Adult; Aged; Aged, 80 and over; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Patient Compliance; Regression Analysis; Salicylates; Stomach Ulcer; Tetracycline

Topics: Aged; Aged, 80 and over; Bismuth; Female; Humans; Organometallic Compounds; Salicylates

Bismuth subsalicylate (BSS), sodium salicylate, and bismuth nitrate were compared with respect to their effects on capsular polysaccharide (CPS) production, bacterial growth inhibition, and potentiation of aminoglycoside inhibition on strains of Gram-negative bacteria. At 250 microM, BSS reduced CPS production in Klebsiella pneumoniae cultures by greater than 90% in contrast to a 36% reduction by salicylate. At 500 microM, salicylate reduced CPS by 52%, versus a 70% reduction by bismuth nitrate. Substantial reduction of CPS production by BSS occurred before bacterial growth inhibition was observed. However, BSS at 250 microM decreased cell viability by 21%, and at 1 mM by 50%. Bismuth nitrate was equally inhibitory to cell growth. Salicylate at 1 mM did not affect bacterial cell counts. The susceptibility of selected Gram-negative bacteria to aminoglycoside antibiotics was studied in the presence of BSS or salicylate. Generally, salicylate at 2.5 mM reduced the concentration of aminoglycoside required to inhibit culture growth for 24 h (IC24) by two-fold. In contrast, 700 microM BSS reduced the IC24 for amikacin four-fold for a resistant K. pneumoniae strain. At 500 microM, BSS reduced the IC24 of gentamicin seven-fold for Salmonella typhimurium. Inhibitory concentrations of amikacin or tobramycin for Enterobacter cloacae or Serratia marcescens were also reduced seven-fold with 500 microM BSS. Bismuth nitrate reduced the IC24 of tobramycin by four-fold for E. cloacae. Thus, the profound effects of BSS on CPS production and aminoglycoside potentiation were due to the additive effects of bismuth and salicylate ions, whilst its effects on growth inhibition were due to the bismuth ion.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Capsules; Bismuth; Drug Synergism; Gram-Negative Bacteria; Klebsiella pneumoniae; Nitrates; Organometallic Compounds; Polysaccharides, Bacterial; Salicylates; Sodium Salicylate

Eradication of Helicobacter pylori infections has proved to be difficult. There is a need both for improved therapies and for ways to rapidly identify therapies that show sufficient promise to be worth pursuing. The objectives of this study were to evaluate the value of a therapeutic regimen of a bismuth salt plus nitrofurantoin for eradication of infection by H. pylori and to determine the validity/utility of the urea breath test in monitoring the progress of a clinical trial. We used an 80% eradication rule to define a promising therapeutic regimen, i.e., a regimen that eradicated the infection (no evidence of infection by H. pylori 4 wk after termination of therapy) in at least 80% of the individuals treated. Eighteen men (median age 38) with documented infection by H. pylori completed the study. At the end-of-study evaluation, H. pylori infection was eradicated (negative urea breath test, culture, and histology) in only one of 18 (5.5%) subjects; 15 were positive by the urea breath test, 16 by culture, 15 by Warthin-Starry stain, and 16 by the presence of acute-on-chronic inflammation. Using the 80% eradication rule, any one of these tests alone would have identified that the combination of antimicrobials tested was not effective in the eradication of the infection. We conclude that the urea breath test is a simple, noninvasive, cost-effective method to separate promising from unpromising candidate therapies and for the evaluation of new therapeutic concepts.

Topics: Adult; Bismuth; Breath Tests; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Nitrofurantoin; Organometallic Compounds; Salicylates; Urea

Topics: Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Bismuth; Drug Therapy, Combination; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Organometallic Compounds; Recurrence; Salicylates

To determine whether Helicobacter pylori has an effect on gastroduodenal mucosal prostaglandin generation, mucosal biopsies were obtained from the gastric body, antrum, and duodenal bulb of 30 patients who were undergoing upper gastrointestinal endoscopy for clinical indications. One biopsy from the gastric body and one from the antrum were tested for urease activity (urea broth) and one biopsy from each area including the duodenum was processed for histology. Two other biopsies form each area were incubated and the accumulation of prostaglandin E2 and 6-keto prostaglandin F1 alpha in the incubation medium was measured by radioimmunoassay. Twelve of the 17 H. pylori-positive patients and seven of the 13 H. pylori-negative patients agreed to take bismuth subsalicylate (Pepto-Bismol) two tablets four times a day for four weeks. One week after treatment, these patients again underwent endoscopy and the above studies. This study indicates that: (1) mucosal PGE2 generation may be increased in the duodenum, gastric body, and antrum in H. pylori-positive patients compared to H. pylori-negative patients, and (2) treatment with bismuth subsalicylate for four weeks results in reduction of mucosal PGE2 in the duodenum, gastric body, and antrum of H. pylori-positive patients and fails to eradicate H. pylori or reduce gastric inflammation.

Topics: Adult; Aged; Aged, 80 and over; Bismuth; Dinoprostone; Duodenitis; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Salicylates

Topics: Bismuth; Child; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Salicylates

Topics: Bismuth; Humans; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; Organometallic Compounds; Salicylates; Syphilis

Known to all as "Montezuma's revenge," "Turista," or the "Aztec two-step," traveler's diarrhea remains the most common and persistent medical complication of international travel. Read on to learn what you need to know about this dreaded condition, especially if your travels this summer will take you beyond the U.S. border.

Topics: Bismuth; Diarrhea; Fluid Therapy; Food Microbiology; Humans; Organometallic Compounds; Risk Factors; Salicylates; Travel; Water Microbiology; Water Supply

Two-hundred and ten consecutive patients undergoing routine gastroscopy were additionally investigated for evidence of Campylobacter pylori (C.p.). 106 patients were positive in one or more tests: 99.1% using a rapid urease detecting test (CLO-test), 80.2% histology, 78.3% cytology and 60% culture. We found no difference between the CLO-test results from biopsies taken from different parts of the stomach in individual patients. C.p. was found in 100% of patients with significant chronic antral gastritis, 67.7% with gastric ulcers, 65% with duodenal ulcers and in 12.1% of normal individuals. The C.p. infection was apparently eliminated in 50% of cases treated with bismuth subsalicylate (BSS) for four weeks. The combination of BSS with amoxicillin, tinidazole or an H2-receptor antagonist offered no advantage over BSS alone. Treatment with BSS led to improvement in symptoms and histological findings including healing of ulcers in patients with or without persistent C.p. infection. The recurrence of C.p. infection after apparently successful treatment was, however, 75% in 4 weeks. In conclusion, C.p. infection correlates strongly with the presence of chronic gastritis, and significantly with gastric and duodenal ulceration. The best diagnostic approach is the combination of a rapid urease detecting test and histology. C.p. infection is of long duration and difficult to eliminate. The most effective treatment for C.p. infection remains BSS as single agent.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Bismuth; Diagnosis, Differential; Drug Therapy, Combination; Female; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Middle Aged; Organometallic Compounds; Prevalence; Salicylates; Tinidazole; Urease

In a prospective open study, 15 patients with ulcerative colitis which was unresponsive to conventional therapy were treated with enemas containing bismuth subsalicylate (700 or 800 mg b.d.). Nine out of the 15 patients showed a significant clinical response, and 6 had gone into complete clinical remission after 8 weeks treatment. Sigmoidoscopoic appearances of the rectal mucosa showed improvement in 9 out of 15 patients at 2 weeks, and 11 out of 15 at 8 weeks. The mucosa appeared sigmoidoscopically normal in 6 out of 15 at 8 weeks. It proved possible to reduce the oral prednisolone dosage from a median of 15 mg/day (range 10 to 35 mg/day) to 6 mg/day (range 0 to 18 mg/day) after 8 weeks of treatment; 5 patients were no longer taking oral steroids at this time. Rectal bismuth subsalicylate appears likely to be an effective therapy in ulcerative colitis and controlled trials are now required.

Topics: Administration, Rectal; Adolescent; Adult; Bismuth; Colitis, Ulcerative; Colon; Female; Humans; Male; Middle Aged; Organometallic Compounds; Salicylates

Plasma bismuth and plasma salicylate concentrations were measured before and after three 30-ml oral doses of bismuth salicylate (Pepto-Bismol liquid) in 10 fasting healthy subjects. From 0 to 120 min following the first dose of bismuth salicylate, the plasma bismuth concentration was less than 1 ng/ml. The peak median plasma bismuth concentration was at +240 min (1.7 ng/ml; range 0.8-5.3 ng/ml). Salicylate appeared in the plasma of all subjects at +30 min, and it reached a peak at +120 min (median 61 mg/L; range 46-104 mg/L). The study demonstrates that, despite rapid and substantial absorption of salicylate, there is negligible absorption of bismuth into the bloodstream from standard oral doses of bismuth salicylate.

Topics: Adult; Bismuth; Female; Humans; Male; Organometallic Compounds; Salicylates; Salicylic Acid

Bismuth subsalicylate was tested in an in vivo perfused rabbit model of oesophagitis for its ability to prevent the mucosal injury caused by pepsin. Treatment efficacy was assessed under both a treatment-before-injury protocol and a treatment-after-injury protocol. Oesophageal mucosal barrier function was evaluated by measuring flux rates of H+, K+, and glucose. The degree of oesophagitis was determined by gross and microscopic examination of the mucosa by several independent observers. Results showed that under both treatment protocols, bismuth subsalicylate significantly reduced the pepsin induced disruption of the mucosal barrier, as well as the morphologic changes. Bismuth subsalicylate when given after exposure to pepsin was also found to protect against the morphologic injury in a dose dependent manner. Experiments in vitro suggested that bismuth subsalicylate inhibits the proteolytic action of pepsin by interacting with pepsin, rather than with the pepsin substrate. We conclude that bismuth subsalicylate can protect the oesophageal mucosa against peptic injury, probably through inactivation of pepsin.

Topics: Animals; Bismuth; Disease Models, Animal; Dose-Response Relationship, Drug; Esophagitis; Esophagus; Mucous Membrane; Organometallic Compounds; Pepsin A; Rabbits; Salicylates

We report two cases of patients with 3-yr histories of upper gastrointestinal symptoms, hyperplastic gastric polyps, and active chronic gastritis. Biopsies retrospectively stained with Giemsa revealed the persistent presence of Helicobacter pylori (HP) in gastric biopsies of both patients throughout the 3 yr. After treatment with amoxicillin and bismuth subsalicylate, both became asymptomatic, one demonstrating disappearance and recurrence of the gastric polyps in conjunction with the HP. These cases demonstrate 3 yr of hyperplastic gastric polyps associated with HP and active gastritis.

Topics: Aged; Amoxicillin; Bismuth; Campylobacter Infections; Chronic Disease; Female; Gastritis; Helicobacter pylori; Humans; Hyperplasia; Middle Aged; Neoplasm Recurrence, Local; Organometallic Compounds; Polyps; Salicylates; Stomach; Stomach Neoplasms

The degree of discomfort and inconvenience caused by travelers' diarrhea highlights the need to prepare the international traveler thoroughly. In addition to observing food and water precautions, most travelers should carry antibiotics and antimotility agents to be started if diarrhea occurs. Used judiciously, these precautions may prevent an unplanned tour of bathrooms and outhouses in foreign countries.

Topics: Bismuth; Campylobacter jejuni; Diarrhea; Dysentery, Bacillary; Food Contamination; Giardiasis; Humans; Organometallic Compounds; Rotavirus Infections; Salicylates; Salmonella Infections; Sulfonamides; Travel

Topics: Administration, Oral; Bismuth; Duodenal Ulcer; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Salicylates

Topics: Acquired Immunodeficiency Syndrome; Antidiarrheals; Bismuth; Brain Diseases; Diarrhea; Humans; Intestinal Absorption; Male; Middle Aged; Myoclonus; Organometallic Compounds; Salicylates

An exaggerated increase in meal-stimulated gastrin is a common finding in patients with duodenal ulcer. Duodenal ulcer patients also exhibit an increase in the number of parietal cells, which results in an increase in maximum acid output. There are also data to suggest that acid hypersecretion may not predate the ulcer disease, but is acquired, possibly due to the trophic effects of the exaggerated gastrin release on parietal cells. We investigated meal-stimulated gastrin release in nine Helicobacter pylori-infected individuals; eight patients with chronic duodenal ulcer and one H. pylori-infected healthy control, both before and after therapy designed to eradicate H. pylori infection. We also simultaneously measured intragastric pH in six duodenal ulcer patients. Eradication of the H. pylori infection reversed the exaggerated meal-stimulated gastrin release (gastrin secretion fell from 141 + 16 pg/ml/h before treatment to 98 +/- 7 pg/ml/h after, p less than 0.01) without affecting intragastric pH. Whereas exaggerated meal-stimulated gastrin release may be an important pathogenetic feature of duodenal ulcer disease, we conclude that it is secondary to the H. pylori infection. This study provides further insight into the role of H. pylori in the pathogenesis of duodenal ulcer disease. We postulate that reversal of the abnormalities in gastrin secretion will be associated with a gradual return of gastric secretion to normal.

Topics: Bismuth; Campylobacter Infections; Drug Therapy, Combination; Duodenal Ulcer; Female; Food; Gastrins; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Tetracycline

Topics: Bismuth; Humans; Organometallic Compounds; Salicylates; Stomatitis; Tooth Discoloration

Infant mice were used for the evaluation of the efficacy of bismuth subsalicylate (BSS) in the prevention of the growth of Campylobacter jejuni in the intestine. The MIC90 of ten C. jejuni strains was 900 micrograms/ml. Of three dosage regimens tested, continuous treatment before and after the bacterial challenge, mimicking the way BSS is used in the prevention of traveller's diarrhoea, was the most effective. Growth inhibition was dose dependent; the high dose of 2000 micrograms per day was more effective than 300 micrograms per day. After cessation of treatment, campylobacter counts increased to the same level as in the control animals.

Topics: Animals; Animals, Newborn; Bismuth; Campylobacter fetus; Campylobacter Infections; Colony Count, Microbial; Diarrhea; Dose-Response Relationship, Drug; Female; Intestines; Male; Mice; Microbial Sensitivity Tests; Organometallic Compounds; Salicylates

Topics: Administration, Oral; Bismuth; Campylobacter Infections; Dose-Response Relationship, Drug; Gastritis; Humans; Organometallic Compounds; Salicylates; Stomach Ulcer

The effect of treatment of Campylobacter pylori-associated gastritis on acid secretion was studied to examine further the strong association between C. pylori and peptic diseases. Twelve symptomatic patients with non-ulcer dyspepsia and C. pylori-associated histologic gastritis had basal and pentagastrin-stimulated gastric acid analysis before and after a 14-day course of amoxicillin 250 mg qid and bismuth subsalicylate 524 mg qid. Endoscopy, antral biopsies, and symptom questionnaires were obtained at entry and at the conclusion of the study. C. pylori was identified by Warthin-Starry stain. Biopsy specimens were also graded for the severity of chronic inflammation and the presence of neutrophils in the epithelium. The treatment regimen cleared C. pylori in 10 of 12 patients. Dyspeptic symptoms improved in 10 of 12 patients, two of whom did not clear the organism, and were unchanged in the remaining two patients, both of whom cleared the bacteria. Neutrophil infiltration in the antral biopsies resolved in 10 patients, including nine with C. pylori clearance and one with persistence of the organism. The severity of the underlying chronic inflammation improved in only one of the 10 organism-free patients and one of the two persistently infected individuals. Pretreatment gastric acid analysis demonstrated hypochlorhydria in three of 12 patients, mild hyperchlorhydria in three of 12 patients, mild hyperchlorhydria in two of 12, and normal acid secretion in the remaining seven patients. Posttreatment acid studies revealed that four of 12 patients were hypochlorhydric, one of 12 had hyperchlorhydria, and seven of 12 were normochlorhydric. After treatment, there was no significant change in basal or maximal acid secretion in the 10 patients who cleared the organism. The two patients who failed to clear C. pylori had insignificant increases in acid secretion after treatment. Our data show no consistent pretreatment pattern of acid secretion in patients with C. pylori-associated gastritis. In addition, gastric acid output did not show a consistent change after treatment for C. pylori. This suggests that the association between C. pylori infection and peptic diseases does not occur via altered acid secretion.

Topics: Amoxicillin; Bismuth; Campylobacter Infections; Drug Therapy, Combination; Gastric Acid; Gastritis; Humans; Organometallic Compounds; Salicylates

To document the diagnostic features of foreign-body pneumonias, four commonly used orally administered medicaments were instilled into the lungs of Sprague-Dawley rats. Rats in each group received a single 0.4 ml dose of either barium sulfate suspension (BaSO4), mineral oil, Pepto-bismol, or Kaopectate inoculated into a lung via a mainstem bronchus. The other lung served as a non-inoculated control. Rats were euthanatized on post-inoculation day 2 or 7 in order to document fully-developed acute pulmonary lesions and developing, chronic pulmonary lesions, respectively. Light microscopic features of BaSO4-inoculated lungs were distinctive from changes in mineral oil-inoculated lungs at both post-inoculation days. On post-inoculation day 2, rats inoculated with BaSO4 had pneumonia characterized by large numbers of alveolar macrophages containing green-to-brown granular material. There was minimal interstitial involvement. On post-inoculation day 2, mineral oil caused pneumonia characterized by giant cells and alveolar macrophages that had cytoplasms distended with variably-sized clear vacuoles. Lungs inoculated with BaSO4 or mineral oil had changed little on post-inoculation day 7 compared to the light microscopic features observed on day 2. On post-inoculation day 2, rats inoculated with either Pepto-bismol or Kaopectate had broncho-interstitial pneumonia with areas of necrosis and hemorrhage. On post-inoculation day 7, lungs inoculated with Pepto-bismol or Kaopectate had extensive fibrosis within alveolar lumens. Energy dispersive spectroscopy performed on sections of lung from rats given BaSO4, Pepto-bismol, and Kaopectate yielded a unique elemental spectrum for each compound in situ on post-inoculation days 2 and 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Barium Sulfate; Bismuth; Drug Combinations; Electron Probe Microanalysis; Female; Kaolin; Lung; Mineral Oil; Organometallic Compounds; Pectins; Pneumonia, Aspiration; Rats; Rats, Inbred Strains; Salicylates

Topics: Adolescent; Amoxicillin; Bismuth; Campylobacter Infections; Child; Child, Preschool; Chronic Disease; Gastritis; Humans; Infant; Organometallic Compounds; Salicylates

Topics: Bismuth; Cisplatin; Female; Humans; Kidney Diseases; Organometallic Compounds; Ovarian Neoplasms; Salicylates

Topics: Anti-Ulcer Agents; Bismuth; Cimetidine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Duodenal Ulcer; Humans; Male; Middle Aged; Organometallic Compounds; Ranitidine; Recurrence; Salicylates

Bismuth subsalicylate (BSS) is a compound without significant aqueous solubility that is widely used for the treatment of gastrointestinal disorders. BSS was able to bind bacteria of diverse species, and these bound bacteria were subsequently killed. A 4-log10 reduction of viable bacteria occurred within 4 h after a 10 mM aqueous suspension of BSS was inoculated with 2 x 10(6) Escherichia coli cells per ml. Binding and killing were dependent on the levels of inoculated bacteria, and significant binding but little killing of the exposed bacteria occurred at an inoculum level of 2 x 10(9) E. coli per ml. Intracellular ATP decreased rapidly after exposure of E. coli to 10 mM BSS and, after 30 min, was only 1% of the original level. Extracellular ATP increased after exposure to BSS, but the accumulation of extracellular ATP was not sufficient to account for the loss of intracellular ATP. The killing of bacteria exposed to BSS may have been due to cessation of ATP synthesis or a loss of membrane integrity. Bactericidal activity of BSS was also investigated in a simulated gastric juice at pH 3. Killing of E. coli at this pH was much more rapid than at pH 7 and was apparently due to salicylate released by the conversion of BSS to bismuth oxychloride. It is proposed that the binding and killing observed for BSS contribute to the efficacy of this compound against gastrointestinal infections such as traveler's diarrhea.

Topics: Adenosine Triphosphate; Bacteria; Bismuth; Campylobacter; Culture Media; Escherichia coli; Gastric Juice; Hydrogen-Ion Concentration; Organometallic Compounds; Protein Binding; Salicylates; Salmonella typhimurium; Serum Albumin; Staphylococcus aureus

The relationship between Campylobacter pylori (CP), histologic gastritis, and dyspeptic symptoms is becoming gradually clearer, but there is still a lack of knowledge of the natural history of treated or untreated gastritis. We examined serial biopsies from the gastric fundus, body, and antrum, and from the duodenum in 16 dyspeptic patients. Patients with concomitant peptic ulcers, alcoholism, or nonsteroidal anti-inflammatory drug use were excluded. CP was present in the biopsies of 50% of patients at presentation. When CP was present, the antrum was always infected, and often had the highest density of organisms. In the duodenum, CP was found only in areas of gastric metaplasia. The presence of CP was highly correlated with gastritis activity (neutrophilic infiltrate). A 4-yr follow-up study of symptoms, endoscopic appearance, and histologic findings including the presence of CP was performed in 10 of the original 16 patients. After 4 yr, both the severity and frequency of epigastric pain remained the same in seven patients, worsened in one, and improved in two. All patients who had CP at initial presentation retained the organism (5/10), whereas none of the previously noninfected patients acquired the infection (5/10). Both CP-positive and -negative patients were treated for 3 wk with 524 mg bismuth subsalicylate qid, and for the first 2 of 3 wk with 250 mg metronidazole qid. One patient who was CP positive was lost to follow-up. In three of the remaining four patients on this regimen, the organism was eradicated. Of the nine patients who completed the treatment program, two had no change in symptoms and seven improved. CP was present in three of seven with improved symptoms and in one of two with no change in symptoms. After treatment, the only change in histology was the disappearance of activity in the CP-positive patients who lost the organism. In conclusion, CP was present in 50% of dyspeptic patients with endoscopic evidence of at least one erosion. Both the symptoms and CP persisted for 4 yr. Dyspeptic symptoms improved after bismuth subsalicylate/metronidazole therapy, regardless of the presence or absence of CP, although the regimen did succeed in eradicating the organism in three of the four CP-positive patients who completed the study.

Topics: Adolescent; Adult; Aged; Bismuth; Campylobacter; Duodenitis; Dyspepsia; Endoscopy; Gastric Mucosa; Gastritis; Humans; Metronidazole; Middle Aged; Organometallic Compounds; Pyloric Antrum; Salicylates

Many studies have been done which show the association of Campylobacter pylori with active gastritis. All types of peptic ulcer disease have shown a positive correlation with the presence of Campylobacter pylori. Clearance of this specific infection has shown histologic improvement as well as decreasing recurrence of peptic ulcer disease. This study demonstrates with statistical validity that treatment with both antibiotics and Bismuth subsalicylate results in improvement in symptoms for as long as five months.

Topics: Amoxicillin; Bismuth; Campylobacter Infections; Humans; Organometallic Compounds; Salicylates

The minimum inhibitory concentrations of five bismuth salts (bismuth subcitrate, bismuth subgallate, bismuth subnitrate, bismuth subsalicylate and tripotassium dicitrato bismuthate, a water soluble compound of bismuth subcitrate) were assayed against 48 strains of Campylobacter pylori employing the agar dilution method. Tripotassium dicitrato bismuthate was most effective (MIC50 8 mg/l), the other bismuth salts exhibited somewhat lower inhibitory activities. It is concluded that bismuth salts are suitable agents for inhibiting growth of Campylobacter pylori.

Topics: Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Campylobacter; Gallic Acid; Humans; Molecular Structure; Organometallic Compounds; Salicylates

Topics: Bismuth; Humans; Organometallic Compounds; Salicylates; Salicylic Acid

Topics: Bismuth; Child; Humans; Nonprescription Drugs; Organometallic Compounds; Reye Syndrome; Salicylates

Campylobacter pylori infection has been associated with duodenal ulcer, gastric ulcer, and non-ulcer dyspepsia. Although in vitro studies have shown that C. pylori is susceptible to most commonly used antibiotics, predictions from in vitro sensitivity studies have not led to a safe and generally effective therapy; C. pylori has proved to be very difficult to eradicate in vivo. We used the urea breath test to assess the susceptibility of C. pylori in vivo to various drugs. C. pylori was susceptible to bismuth subsalicylate, bismuth subnitrate, and furazolidone. C. pylori was not susceptible (i.e., urease activity remained despite administration of the drug) to the following drugs: 1) antiulcer agents (cimetidine, ranitidine, famotidine, omeprazole, misoprostol, sucralfate, liquid antacids); 2) NSAIDs (aspirin, indomethacin, ibuprofen, naproxen, tolmetin); 3) antibiotics (oral penicillin V, trimethoprim-sulfamethoxazole, dicloxacillin); 4) salts (lithium, ferrous sulfate, gold); 5) miscellaneous (acetaminophen, phenytoin, hydrochlorothiazide, propranolol, metoprolol, metoclopramide, ursodeoxycholic acid). Oral antimicrobials can be administered directly onto the site of infection, so that a very low oral dose will provide many multiples of the in vitro minimal inhibitory concentration. Furazolidone suspension (7 mg) was administered seven times daily (daily dose 49 mg) to three individuals infected by C. pylori during suppression of gastric acid secretion with famotidine (40 mg bid). After 4 days, all subjects had significant reductions in urease activity (two to normal and one to a borderline value). This response suggested that very low-dose therapy may be useful either alone or combined with bismuth. Conclusive establishment of an etiologic (or major contributory) relationship of C. pylori to ulcer disease will require a safe and reliable method to eradicate the organism from the stomach and duodenum.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bismuth; Breath Tests; Campylobacter; Campylobacter Infections; Duodenum; Humans; Organometallic Compounds; Salicylates; Stomach

Topics: Amoxicillin; Bismuth; Campylobacter Infections; Drug Therapy, Combination; Gastric Mucosa; Gastritis; Humans; Metronidazole; Organometallic Compounds; Peptic Ulcer; Salicylates

Three pilot studies were performed to evaluate the efficacy of bismuth subsalicylate (BSS) and nitrofurantoin to eradicate Campylobacter pylori colonization in man. Nitrofurantoin 3 x 100 mg capsules for 10 days did not clear C. pylori in any of 13 patients, and neither did the combination of BSS and nitrofurantoin suspension (0/6 patients). Immediately after high dose BSS therapy 3 x 900 mg for 28 days, 8/17 patients (47%) had negative cultures and rapid urease tests. There was recrudescence in 5 out of 6 patients so far submitted to follow-up investigations, giving a best possible outcome estimate of 18% and a worst possible eradication rate of 6% in this study. Preliminary data indicate that triple therapy may be a more effective option, but doubts remain as to whether the puristic therapeutic goal of complete bacterial eradication can be safely and effectively achieved with presently available drugs.

Topics: Adult; Biopsy; Bismuth; Campylobacter Infections; Drug Therapy, Combination; Duodenal Ulcer; Dyspepsia; Female; Humans; Male; Middle Aged; Nitrofurantoin; Organometallic Compounds; Pilot Projects; Pyloric Antrum; Salicylates; Stomach Ulcer; Urease

37 patients with epigastric pain and chronic erosive gastritis underwent an open controlled therapeutic trial with bismuthsubsalicylate (BS). Group A (21 patients) was treated with BS, liquid, 4 X 314 mg for three weeks, group B (16 patients) with BS tablets, 3 X 300 mg for two weeks. A significant reduction of symptoms (p less than 0.001) and endoscopically assessed chronic erosions (p less than 0.001) was achieved in both groups. Campylobacter pylori was detected in 89% of the patients before treatment, but was absent in 78% of the patients after treatment. The histological grading of antral mucosa showed a significant reduction (p less than 0.001) of polymorphonuclear cell (PML) infiltration after two and three weeks treatment respectively. While in group A PML cells had disappeared from gastric mucosa in all but two patients, in group B 50% of the patients had some degree of PML cell infiltration left in the antral mucosa. This study confirms the beneficial effect of BS in the treatment of C. pylori associated active chronic gastritis and reemphasizes the pathogenetic role of C. pylori in this disease.

Topics: Adult; Bismuth; Campylobacter; Chronic Disease; Female; Gastritis; Gastroscopy; Humans; Male; Middle Aged; Organometallic Compounds; Pyloric Antrum; Salicylates; Stomach

We evaluated the efficacy of medical therapy, consisting of liquid bismuth subsalicylate prescribed either in combination with oral ampicillin (n = 15) or alone (n = 1), in the clearing of bacterial colonization on the antrum in 16 children with Campylobacter pylori-associated antral gastritis. We also examined the effects of medical treatment on altering the severity of associated antral inflammation. Eight patients had upper gastrointestinal tract hemorrhage, two had acute gastric outlet obstruction, and 10 had symptoms of episodic epigastric abdominal pain. Duodenal ulcers were demonstrated in 10 of the 16 patients; in the other six, C. pylori-associated antral gastritis was documented without evidence of acute peptic ulceration. Seven days after a 6-week course of medical therapy, repeat upper endoscopy plus mucosal biopsy specimens showed that C. pylori colonization of the antrum had cleared in 12 of the 16 (75%) patients. Inflammation in the antrum improved in all patients in whom colonization by C. pylori was eradicated. In contrast, in the four with persistent colonization of the antrum, the severity of antral gastritis had not improved (p less than 0.01). Clinical symptoms improved in 9 of 12 patients in whom C. pylori colonization was no longer present, whereas subjective symptoms were unaffected in those with continued bacterial colonization of the antrum (p less than 0.05). We conclude that oral bismuth subsalicylate, in conjunction with ampicillin, can eradicate C. pylori colonization of the antrum, and that clearing of C. pylori is correlated with an improvement in the associated antral gastritis and clinical symptoms. These findings provide additional support for the hypothesis that these gastric organisms could play an etiologic role in primary antral gastritis and peptic ulcer disease.

Topics: Adolescent; Ampicillin; Bismuth; Campylobacter; Campylobacter Infections; Child; Drug Therapy, Combination; Duodenal Ulcer; Gastritis; Humans; Organometallic Compounds; Pyloric Antrum; Salicylates

The gastric and tracheal flora of 142 consecutive patients receiving stress ulcer prophylaxis were investigated, identifying identical isolates by typing. Furthermore, the growth pattern of normal respiratory bacteria and organisms causing ventilation pneumonia at different pH values and the in vitro effect of sucralfate and bismuth subsalicylate on these bacteria in simulated gastric fluid were studied. The results obtained were as follows: (1) with rising gastric pH bacterial counts in gastric aspirates, especially gram-negatives, increased significantly; (2) in 45 (31.7%) of the patients identical organisms were first isolated in gastric samples and one to two days later in tracheal secretions; (3) ventilation pneumonia was significantly more frequent in patients with high gastric pH; (4) pathogens causing ventilation pneumonia grew well in simulated gastric fluid at higher pH values, unlike normal respiratory organisms; and (5) sucralfate and bismuth subsalicylate showed antibacterial activity against frequent causative organisms of ventilation pneumonia.

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Gastric Juice; Humans; Hydrogen-Ion Concentration; Organometallic Compounds; Peptic Ulcer; Pneumonia; Prospective Studies; Respiration, Artificial; Risk Factors; Salicylates; Stress, Physiological; Sucralfate; Trachea

In a prospective open study 21 patients with upper abdominal complaints and chronic active gastritis as well as endoscopically proven erosions were treated with bismuth subsalicylate (4 X 30 ml/day, corresponding to 4 X 314 mg Bi3+) for three weeks. In 20 patients (95%) Campylobacter pylori (CP) was found in at least two of three examinations (culture, CLO quick-test, special histology). After the treatment 17 of 21 patients (81%) were CP negative, and the clinical symptoms had gradually disappeared. The histologically demonstrated degree of activity had regressed significantly after the three-week treatment; in 90% of patients the inflammatory process had completely abated. These results demonstrate that bismuth subsalicylate is highly effective in the acute treatment of CP-associated chronic erosive gastritis.

Topics: Adult; Aged; Biopsy; Bismuth; Campylobacter; Campylobacter Infections; Chronic Disease; Drug Evaluation; Female; Gastric Mucosa; Gastritis; Gastroscopy; Humans; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged; Organometallic Compounds; Salicylates

Topics: Anti-Bacterial Agents; Bismuth; Campylobacter Infections; Erythromycin; Erythromycin Ethylsuccinate; Gastritis; Humans; Organometallic Compounds; Salicylates

Topics: Adult; Antidiarrheals; Bismuth; Colitis; Humans; Male; Organometallic Compounds; Salicylates

The in vitro susceptibility of recent Danish human clinical isolates of Campylobacter pyloridis to cimetidine, sucralfate, bismuth subsalicylate and sixteen antimicrobial agents was determined by an agar-dilution technique. Benzylpenicillin was the most active drug (MIC90 = 0.1 microgram/ml); ampicillin, erythromycin, gentamicin and ciprofloxacin were slightly less active. All strains were resistant to 100 micrograms sulfamethizole, and nalidixic acid also had little activity on weight basis. Of the three anti-peptic ulcer drugs, bismuth subsalicylate was most active (MIC90 25 micrograms/ml), but sucralfate and cimetidine also had antibacterial activity, although only little (MIC90 3200 micrograms/ml).

Topics: Anti-Bacterial Agents; Bismuth; Campylobacter; Cimetidine; Humans; Microbial Sensitivity Tests; Organometallic Compounds; Salicylates; Sucralfate

Topics: Bacteria; Bismuth; Gastric Juice; Humans; Organometallic Compounds; Salicylates; Sucralfate

Colloidal bismuth subcitrate (CBS) precipitates in an acid environment, adheres to mucus, blocks pepsin activity, retards hydrogen-ion back diffusion and stimulates prostaglandin synthesis. The average healing rate after 4 weeks' treatment with CBS is 78% in duodenal ulcer versus 67% with cimetidine. A direct comparison with ranitidine gives healing rates of 78% (CBS) as opposed to 78% with ranitidine. The corresponding figures in gastric ulcer are 68% (CBS) and 54% (cimetidine). The percentage of relapse-free patients is substantially higher after CBS ulcer healing than after H2-blockers. Bismuth subsalicylate eliminates Campylobacter pylori in 71% after 4-weeks' therapy. Parallel to this elimination a decrease and normalization of the acute inflammatory process can be seen in antral mucosa.

Topics: Anti-Ulcer Agents; Bismuth; Campylobacter Infections; Chronic Disease; Duodenal Ulcer; Gastritis; Humans; Organometallic Compounds; Peptic Ulcer; Salicylates; Stomach Ulcer

Topics: Adolescent; Bismuth; Child; Humans; Organometallic Compounds; Reye Syndrome; Salicylates

Topics: Bismuth; Diarrhea; Humans; Organometallic Compounds; Salicylates

Bismuth salts inhibited plaque formation of all enteric viruses tested, which included four strains of rotavirus and one strain each of echovirus, reovirus, and poliovirus. The compounds had no direct virucidal effect at concentrations ranging from 0.025 to 2.5 mg/ml, and the inhibitory effects were observed only at concentrations slightly below those that caused extensive cytotoxicity. Plaque inhibition appeared to result from interference with host cell functions, with secondary inhibition of virus production.

Topics: Animals; Bismuth; Cattle; Cells, Cultured; Enterovirus; Humans; Organometallic Compounds; Rotavirus; Salicylates; Tartrates; Viral Plaque Assay

An investigation was done on the action in vitro of two pharmaceutical preparations containing Bi, De Nol and Pepto Bismol, on the fermentative capacity of intestinal bacteria. For the purpose, using an instrument and a technique previously described, fecal fermentation (FF) was measured in 21 stool samples, to which lactose was added to assure appreciable levels of fermentation. In 11 of the samples, FF was measured without and with addition of De Nol; and in the 10 remaining samples, without and with addition of Pepto Bismol. In 7 of the samples with which the action of De Nol was studied, this preparation significantly reduced FF from 10.9 not equal to 4.3 (mean not equal to s. d.) to 4.9 not equal to 5.0 ml of gas/24 h (p less than 0.02); on the contrary, in the 4 remaining samples, it increased FF, although not significantly, from 8.7 not equal to 4.8 to 16.7 not equal to 8.8 ml of gas/24 h (N.S.). Pepto Bismol significantly reduced FF, in all the 10 samples with which the action of that pharmaceutical - preparation was investigated, from 11.7 not equal to 6.1 to 3.0 not equal to 2.1 ml of gas/24 L (p less than 0.0001). A discussion was done on the possible mechanisms of the antifermentative action of Bi, as well as on the probable usefulness of De Nol and Pepto Bismol for the control of exaggerated intestinal fermentation and the flatulence it frequently causes.

Topics: Antacids; Bacteria; Bismuth; Feces; Fermentation; Humans; In Vitro Techniques; Intestines; Lactose; Organometallic Compounds; Salicylates

In view of all the controversy surrounding travelers' diarrhea, how should patients be counseled regarding its prevention and treatment? First, all patients should be instructed on the importance of eating and drinking only safe food and water and on methods of dietary manipulation and oral rehydration therapy. The travelers listed in table 4, as well as short-term visitors to Mexico, may be candidates for prophylactic medication unless such treatment is contraindicated. All patients can be offered an antimotility agent for discriminant use as discussed, and a prescription for trimethoprim-sulfamethoxazole is generally a good idea in the event of a severe bout of illness during travel. A traveler can go overboard in an attempt to avoid diarrheal illness. Such overconcern can detract from the enjoyment of travel and limit the spectrum of activities and cuisine. One report noted that diarrhea seemed to occur more frequently the more a traveler tried to elude it! This could well set the stage for the biggest controversy of all.

Topics: Antidiarrheals; Bismuth; Diarrhea; Doxycycline; Drug Combinations; Food; Humans; Organometallic Compounds; Risk; Salicylates; Sulfamethoxazole; Terminology as Topic; Travel; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vaccination

We investigated the capability of Pepto-Bismol and its components (Veegum and bismuth subsalicylate) to sequester bile acids from aqueous solution in vitro and compared it to that of cholestyramine. Through a pH range of 3-9, all substances tested sequestered free and conjugated bile acids in quantities directly related to the concentration of the sequestering agent within the incubation mixture. Veegum was more effective gram for gram than bismuth subsalicylate. Pepto-Bismol, whose sequestering capacity approximated cholestyramine's, absorbed more than either of its components alone. The relationship between Pepto-Bismol's in vitro bile acid binding and its in vivo antidiarrheal properties is unknown.

Topics: Adsorption; Bentonite; Bile Acids and Salts; Bismuth; Cholestyramine Resin; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Hydrogen-Ion Concentration; In Vitro Techniques; Organometallic Compounds; Salicylates; Solutions

Each year, more than one million American travelers develop diarrhea, usually due to toxin-producing Escherichia coli. Traveler's diarrhea can be prevented with bismuth subsalicylate or doxycycline, but neither is suitable for pediatric patients. Trimethoprim-sulfamethoxazole is effective for prophylaxis and treatment in adults. It is also safe for children and may prove to be efficacious. It may be possible to avoid widespread prophylaxis and to give medication only if diarrhea develops.

Topics: Bismuth; Child; Diarrhea; Doxycycline; Drug Combinations; Escherichia coli Infections; Humans; Organometallic Compounds; Premedication; Salicylates; Sulfamethoxazole; Travel; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Bismuth; Diarrhea; Doxycycline; Drug Combinations; Escherichia coli Infections; Humans; Organometallic Compounds; Salicylates; Sulfamethoxazole; Travel; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Bismuth; Diarrhea; Humans; Organometallic Compounds; Salicylates; Travel

Topics: Bismuth; Diarrhea; Humans; Hypercalcemia; Organometallic Compounds; Risk; Salicylates; Travel

Topics: Adult; Bismuth; Child; Diarrhea; Humans; Organometallic Compounds; Salicylates; Travel

Topics: Bismuth; Color; False Positive Reactions; Feces; Female; Gastrointestinal Hemorrhage; Heme; Humans; Infant; Organometallic Compounds; Salicylates

Topics: Bismuth; Diarrhea; Doxycycline; Drug Combinations; Humans; Organometallic Compounds; Salicylates; Sulfamethoxazole; Travel; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Bismuth; Diarrhea; Doxycycline; Fluid Therapy; Humans; Organometallic Compounds; Salicylates; Travel

Topics: Bismuth; Brain Diseases; Humans; Male; Middle Aged; Organometallic Compounds; Salicylates

The active ingredient in Pepto-Bismol (PB) (Norwich-Eaton), a common antidiarrheal, is bismuth subsalicylate. The absorption of salicylate after oral PB was studied in six fasted men. Plasma concentrations of total salicylate and the urinary excretion profile of salicylate were determined as a function of time and dose. After 60 ml PB, 500.1 +/- 33.6 mg (mean +/- SD) salicylate were recovered in urine, representing 95.0 +/- 6.4% of salicylic acid equivalents in 60 ml of the formulation. Peak plasma salicylate levels were reached 0.5 to 3 hr after ingestion and averaged 40.1 +/- 17.3 micrograms/ml. Absorption of salicylate was also essentially complete after 15- and 30-ml doses of the antidiarrheal preparation, and a linear relationship between dose and recovery of salicylate in the urine was found. Salicylate kinetics was nonlinear after a multiple-dose regimen of 60 ml every 6 hr for five doses.

Topics: Adult; Bismuth; Half-Life; Humans; Intestinal Absorption; Kinetics; Male; Organometallic Compounds; Salicylates

Topics: Adult; Bismuth; Child; Humans; Intestinal Absorption; Male; Organometallic Compounds; Salicylates

Topics: Bismuth; Diarrhea; Doxycycline; Humans; Organometallic Compounds; Salicylates; Travel

Topics: Acute Disease; Adult; Bismuth; Diarrhea; Humans; Organometallic Compounds; Salicylates; Travel

Topics: Animals; Aspirin; Bismuth; Feces; Gastrointestinal Hemorrhage; Male; Occult Blood; Organometallic Compounds; Rats; Salicylates

Topics: Antidiarrheals; Bismuth; Drug Interactions; Humans; Nonprescription Drugs; Organometallic Compounds; Salicylates

Topics: Bismuth; Diarrhea; Humans; Organometallic Compounds; Salicylates; Travel

Topics: Bismuth; Gastrointestinal Diseases; Humans; Male; Organometallic Compounds; Salicylates

Four adsorbant drug preparations, Kaopectate, colloidal Attapulgite, noncolloidal Attapulgite and Pepto-bismol were investigated for their effects on fluid accumulation in ligated segments of pig intestine inoculated with enteropathogenic Escherichia coli. Two anti-inflammatory drugs. aspirin and methylprednisolone, and two antibiotics, lincomycin and polymyxin B, were also tested. All the drugs except the two anti-inflammatory products were given by injection into the lumen of the intestine. Aspirin was given orally and methylprednisolone was given intramuscularly. The antibiotics were tested at levels at which they had no significant antibacterial effect in in vitro tests. The adsorbant drugs colloidal Attapulgite and Pepto-bismol were shown to be effective in reducing fluid accumulation in ligated segments of pig intestine infected with enteropathogenic E. coli. In the case of Peptobismol this effect was associated with an antibacterial effect as well as an antitoxic effect, probably due to its adsorbant properties. It is possible that an aspirin-like effect in the gut due to the active ingredient bismuth subsalicylate may have contributed to the effectiveness of Pepto-bismol. Colloidal Attapulgite was demonstrated to have an antitoxic effect but did not have an antibacterial effect. In high doses, the anti-inflammatory drugs acetylsalicylic acid and methylprednisolone were marginally effective in reduction of fluid accumulation in the same test system. Lincomycin was shown to reduce intestinal fluid secretion, whereas polymyxin B had no effect.

Topics: Animals; Anti-Inflammatory Agents; Antidiarrheals; Aspirin; Bismuth; Enterotoxins; Escherichia coli; Escherichia coli Infections; Intestinal Secretions; Jejunum; Kaolin; Ligation; Lincomycin; Methylprednisolone; Organometallic Compounds; Pectins; Polymyxin B; Salicylates; Swine; Swine Diseases

The inhibition of the activity of enterotoxins by bismuth salts was assessed in laboratory models. In the Y-1 adrenal cell tissue culture system, a commercial preparation containing bismuth subsalicylate reduced the activity of crude toxin from Vibrio cholerae by 10(4)-fold as compared with the activity of controls. Similar results were obtained with use of the adult rabbit ligated intestinal loop model. The preparation failed to affect crude Escherichia coli or cholera toxin activity once these toxins had become bound to intestinal mucosa. Pretreatment of ligated loops with the preparation reduced the fluid accumulation mediated by crude E. coli and cholera toxins by 78% and 91%, respectively. Bismuth subsalicylate and the complex vehicle of the preparation also inactivated toxin; however, bismuth subsalicylate was more effective when combined with the vehicle. Bismuth subcarbonate failed to inhibit fluid accumulation in ligated loops. Preparations containing bismuth subsalicylate may be effective in the prevention of diarrhea mediated by toxigenic E. coli.

Topics: Animals; Bacterial Toxins; Bismuth; Cells, Cultured; Cholera Toxin; Enterotoxins; Escherichia coli; Ileum; Intestinal Mucosa; Organometallic Compounds; Rabbits; Salicylates; Water

Topics: Adsorption; Aluminum Hydroxide; Antacids; Antidiarrheals; Bismuth; Chlortetracycline; Organometallic Compounds; Oxytetracycline; Salicylates

Topics: Antacids; Antidiarrheals; Bismuth; Follow-Up Studies; Organometallic Compounds; Penicillins; Salicylates; Syphilis

Topics: Animals; Arsenicals; Bismuth; Organometallic Compounds; Peanut Oil; Penicillin G Procaine; Penicillins; Plant Oils; Rabbits; Salicylates; Stearic Acids; Syphilis

Topics: Antacids; Bismuth; Organometallic Compounds; Penicillin G; Penicillins; Salicylates; Sodium Chloride; Syphilis

Topics: Antacids; Bismuth; Organometallic Compounds; Penicillin G; Penicillins; Salicylates; Sodium Chloride; Syphilis

Topics: Animals; Antacids; Arsenicals; Bismuth; Organometallic Compounds; Rabbits; Salicylates; Syphilis

Topics: Bismuth; Humans; Opium; Organometallic Compounds; Salicylates; Stomach

Topics: Bismuth; Organometallic Compounds; Salicylates; Syphilis

Topics: Antacids; Antidiarrheals; Bismuth; Humans; Injections; Organometallic Compounds; Plant Oils; Salicylates

Topics: Bismuth; Fusobacterium Infections; Gingivitis, Necrotizing Ulcerative; Organometallic Compounds; Salicylates

Topics: Antacids; Bismuth; Fusobacterium Infections; Gingivitis, Necrotizing Ulcerative; Organometallic Compounds; Salicylates