piperidines and Lung-Diseases

Small molecule tyrosine kinase inhibitors [smTKI, comprising mostly of Janus kinase (JAK) and to a lesser extent, spleen tyrosine kinase (SyK) inhibitors] modulate the cytokine receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies. As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical.. We performed a systematic review and meta-analysis of all published trial data on the pulmonary and serious adverse effects of smTKIs in autoimmune disease. EMBASE, MEDLINE, CENTRAL and Pneumotox databases were searched up to April 2019 for randomized controlled trials, observational studies and post marketing surveillance, comparing any smTKI with placebo or another therapy, or as monotherapy at different doses. Primary outcomes comprised of any respiratory complications including upper and lower respiratory tract infections (URTI, LRTI), influenza, pneumonia, opportunistic respiratory infections, drug-induced interstitial lung disease, pulmonary embolism and lung neoplasm.. We identified 4667 citations for screening, and selected 319 studies for full text review. Seventy-nine studies were analysed, including 47 randomized controlled trials, 25 observational studies and seven post-marketing surveillance studies, comprising 159 652 participants. There were significantly increased risks of URTI [risk difference (RD) 0.03; 95% CI: 0.01, 0.05; P = 0.00; 36 studies, 14 724 participants], LRTI (RD 0.01; 95% CI: 0.00, 0.02; P = 0.02; 24 studies, 12 302 participants), influenza (RD 0.01; 95% CI: 0.00, 0.01; P = 0.04; 22 studies, 10 684 participants), and pneumonia (RD 0.00; 95% CI: 0.00, 0.01; P = 0.02; 33 studies, 15 511 participants). No increased risk was found for other respiratory complications, including pulmonary embolism.. SmTKI increases the risk of non-opportunistic respiratory infections compared with placebo. The risk of any serious pulmonary adverse events is low.

Topics: Adult; Aged; Autoimmune Diseases; Female; Humans; Janus Kinase Inhibitors; Lung Diseases; Male; Middle Aged; Piperidines; Product Surveillance, Postmarketing; Pyrimidines; Randomized Controlled Trials as Topic; Small Molecule Libraries

The medical and social impact of cough is substantial. Current antitussive agents at effective doses have adverse events such as drowsiness, nausea and constipation that limit their use. There is also recent evidence that standard antitussive agents, such as codeine, may not reduce cough during upper respiratory infections. Therefore, there is a need for more effective and better-tolerated agents. The efficacy of levocloperastine, a novel antitussive, which acts both centrally on the cough center and on peripheral receptors in the tracheobronchial tree in treating chronic cough, was compared with that of other standard antitussive agents (codeine, levodropropizine and DL-cloperastine) in six open clinical trials. The studies enrolled patients of all ages with cough associated with various respiratory disorders including bronchitis, asthma, pneumonia and chronic obstructive pulmonary disease. Levocloperastine significantly improved cough symptoms (intensity and frequency of cough) in all trials, and improvements were observed after the first day of treatment. In children, levocloperastine reduced nighttime awakenings and irritability, and in adults it was effective in treating cough induced by angiotensin-converting enzyme inhibitors. When compared with other antitussive agents, levocloperastine had improved or comparable efficacy, with a more rapid onset of action. Importantly, no evidence of central adverse events was recorded with levocloperastine, whereas drowsiness was reported by a significant number of patients receiving codeine. Levocloperastine is an effective antitussive agent for the treatment of cough in patients of all ages. It has a more rapid onset of action than standard agents with an improved tolerability profile.

Topics: Adolescent; Adult; Aged; Antitussive Agents; Bronchitis; Chronic Disease; Clinical Trials as Topic; Codeine; Cough; Female; Humans; Lung Diseases; Male; Middle Aged; Patient Selection; Piperidines; Propylene Glycols; Stereoisomerism; Treatment Outcome

To characterise infections in patients with rheumatoid arthritis (RA) in ORAL Surveillance.. In this open-label, randomised controlled trial, patients with RA aged≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg two times per day or a tumour necrosis factor inhibitor (TNFi). Incidence rates (IRs; patients with first events/100 patient-years) and hazard ratios (HRs) were calculated for infections, overall and by age (50-<65 years; ≥65 years). Probabilities of infections were obtained (Kaplan-Meier estimates). Cox modelling identified infection risk factors.. IRs/HRs for all infections, serious infection events (SIEs) and non-serious infections (NSIs) were higher with tofacitinib (10>5 mg two times per day) versus TNFi. For SIEs, HR (95% CI) for tofacitinib 5 and 10 mg two times per day versus TNFi, respectively, were 1.17 (0.92 to 1.50) and 1.48 (1.17 to 1.87). Increased IRs/HRs for all infections and SIEs with tofacitinib 10 mg two times per day versus TNFi were more pronounced in patients aged≥65 vs 50-<65 years. SIE probability increased from month 18 and before month 6 with tofacitinib 5 and 10 mg two times per day versus TNFi, respectively. NSI probability increased before month 6 with both tofacitinib doses versus TNFi. Across treatments, the most predictive risk factors for SIEs were increasing age, baseline opioid use, history of chronic lung disease and time-dependent oral corticosteroid use, and, for NSIs, female sex, history of chronic lung disease/infections, past smoking and time-dependent Disease Activity Score in 28 joints, C-reactive protein.. Infections were higher with tofacitinib versus TNFi. Findings may inform future treatment decisions.. NCT02092467.

Topics: Analgesics, Opioid; Antirheumatic Agents; Arthritis, Rheumatoid; C-Reactive Protein; Female; Humans; Lung Diseases; Piperidines; Pyrimidines; Pyrroles; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha

An inhalation anesthetic-induced attenuation effect on the inflammatory reaction during one-lung ventilation (OLV) has been reported. Pulmonary inflammation is a substantive prognostic factor for Ivor Lewis operations. Blood inflammatory parameters and postoperative pulmonary complications between sevoflurane and propofol-remifentanil anesthesia in patients undergoing Ivor Lewis operations were compared.. A prospective, randomized study.. A medical university.. Forty-eight patients undergoing Ivor Lewis operation allocated randomly into 2 groups.. Patients received sevoflurane or total intravenous anesthesia using propofol and remifentanil (n = 24 per group).. Blood interleukin-6 (IL-6), malondialdehyde (MDA), oxygenation, abnormalities on a chest radiograph (CXR), extubation, intensive care unit (ICU) stay, length of hospitalization, and postoperative complications were compared between the 2 anesthetic techniques. The level of IL-6 at the end of surgery was lower for sevoflurane (69.5 [35.9-121.0] pg/mL) than propofol-remifentanil (128.2 [92.8-163.8] pg/mL, p = 0.03), but this difference was not maintained 24 hours after surgery. Frequencies of abnormalities measured by a CXR, PaO(2)/F(I)O(2)<300, and PaCO(2) <50 mmHg until discharge, the postoperative highest C-reactive protein level, white blood cells, and MDA did not differ between the 2 anesthetics. No differences in the extubation time, ICU stay, discharge day, or the incidence of hospital complications between sevoflurane and propofol-remifentanil anesthesia techniques were observed.. Sevoflurane anesthesia attenuated an increase in blood IL-6 at the end of surgery but did not provide any advantages over propofol remifentanil in terms of postoperative pulmonary complications in Ivor Lewis operations.

Topics: Aged; Anesthesia, Inhalation; Esophagoscopy; Female; Humans; Lung Diseases; Male; Methyl Ethers; Middle Aged; Morbidity; Piperidines; Postoperative Complications; Propofol; Prospective Studies; Remifentanil; Sevoflurane

Remifentanil has a unique metabolic pathway that holds potential benefits for long-term sedation. We compared remifentanil-midazolam to sufentanil-midazolam in 41 critically ill adults requiring mechanical ventilation.. Randomized double-blind trial.. Infusion rates were titrated every 4 hours to achieve the desired Ramsay score. Five fold increases in dose requirement was considered as the development of tolerance. Drugs requirement, development of tolerance and weaning time of ventilation were compared.. The study was stopped after an interim analysis. The remifentanil and sufentanil groups were comparable regarding IGS II: 56+/-22 vs 64+/-26, mean+/-SD, ICU length of stay: 26 (8-45) vs 19 (11-34) days, and sedation duration: 6 (4-19) vs 6 (3-16)days, median [interquartile range, IQR]). There was a shorter weaning time in the remifentanil group as compared to sufentanil group: 22 h (12-53) vs 96 (47-142) h, median [IQR], p=0.04). The daily opioid infusion rate needed to be decreased over time only in sufentanil group, p < 0.001. Tolerance occurred in 6 (30%; CI(95), 10 to 40%) remifentanil and no sufentanil patients (P=0.02).. Sufentanil infusion needed to be reduced over time and prolonged the weaning time when compared to remifentanil.

Topics: Adult; Aged; Conscious Sedation; Critical Care; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Hospital Mortality; Humans; Lung Diseases; Male; Midazolam; Middle Aged; Piperidines; Postoperative Complications; Remifentanil; Respiration, Artificial; Shock; Sufentanil; Ventilator Weaning

Topics: Adrenergic beta-Agonists; Adult; Aerosols; Amino Alcohols; Bronchi; Bronchodilator Agents; Catechols; Dose-Response Relationship, Drug; Heart Rate; Humans; In Vitro Techniques; Infant, Newborn; Isoproterenol; Lung Diseases; Methanol; Middle Aged; Muscle Contraction; Muscle, Smooth; Piperidines; Placebos; Respiration; Spirometry; Stimulation, Chemical; Time Factors

Topics: Carbazoles; Hemorrhage; Humans; Lung Diseases; Piperidines; Pulmonary Alveoli

Sporadic cases of rheumatoid nodules (RNs) in the lung during treatment with tumour necrosis factor (TNF) inhibitors have been reported, but no treatment has been established. Here, we report a case of symptomatic lung RNs refractory to abatacept (ABT) and intravenous cyclophosphamide (IVCY) that improved with tofacitinib (TOF) treatment. A 75-year-old Japanese woman with a 10-year history of rheumatoid arthritis (RA) presented with a cough and haemoptysis during treatment with etanercept (ETN). Radiographic examinations revealed multiple nodules that were diagnosed as lung RNs

Topics: Aged; Arthritis, Rheumatoid; Etanercept; Female; Humans; Lung Diseases; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Rheumatoid Nodule; Tomography, X-Ray Computed; Treatment Outcome; Tumor Necrosis Factor Inhibitors

Divya-Swasari-Vati is a calcium containing polyherbal ayurvedic medicine prescribed for the lung-related ailments observed in the current pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 infections. The formulation is a unique quintessential blend of nine herbs cited in Ayurvedic texts for chronic cough and lung infection. Analytical standardization of herbal medicines is the pressing need of the hour to ascertain the quality compliance. This persuaded us to develop a simple, rapid, and selective high-performance thin-layer chromatographic method for Divya-Swasari-Vati quality standardization. The developed method was validated for the quantification of marker components, gallic acid, cinnamic acid, piperine, eugenol and glycyrrhizin, against reference standards in five different batches of Divya-Swasari-Vati. The analytes were identified by visualization at 254 nm, and by matching their retention factor with authentic standards. The developed method was validated as per the guidelines recommended by the International Council for Harmonization for parameters like, linearity, limit of detection, limit of quantification, accuracy, and precision. Therefore, the developed novel high-performance thin-layer chromatographic process could be employed for rapid standardization of Divya-Swasari-Vati and other related herbal formulation, which would aid in quality manufacturing and product development.

Topics: Alkaloids; Benzodioxoles; Chromatography, Thin Layer; Cinnamates; Eugenol; Gallic Acid; Glycyrrhizic Acid; Humans; Lung Diseases; Medicine, Ayurvedic; Molecular Structure; Piperidines; Plant Extracts; Plants, Medicinal; Polyunsaturated Alkamides

Destombes-Rosai-Dorfman disease (RDD) is a rare multisystemic histiocytosis. Pulmonary involvement during RDD has been poorly described. The goal of this study was to examine the clinical presentations, radiological features, and outcomes of 15 patients with RDD and lung involvement.. The cases of RDD with lung involvement were extracted from the French National Histiocytosis registry. Efficacy of the MEK inhibitor cobimetinib in treating lung disease was evaluated with an. Fifteen patients (six women; median age, 40 years at RDD diagnosis) were included. All patients had evidence of systemic disease with extrapulmonary localizations of the disease (lymphadenopathy [n = 12], skin [n = 9], bones [n = 6], retroperitoneal involvement [n = 3], sinuses [n = 3], parotid gland [n = 2], submandibular gland [n = 1], and breast [n = 1]). Presenting symptoms were dominated by dyspnea and dry cough in seven patients. Restrictive physiology was observed in two of five patients. BAL showed lymphocytosis in one of five cases. Eight patients received corticosteroids, all but one with variable immunosuppressive or immunomodulatory therapies. Two patients received cobimetinib for severe lung disease, with dramatic pulmonary metabolic and tumoral responses. Two patients died during follow-up: one of hemoptysis, and the other of an unrelated cerebral tumor.. Pulmonary involvement in RDD is rare, proteiform, and sometimes severe. The MEK inhibitor cobimetinib can lead to dramatic responses.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Azetidines; Bronchoalveolar Lavage Fluid; Cough; Dyspnea; Female; Fluorodeoxyglucose F18; France; Histiocytosis, Sinus; Humans; Immunosuppressive Agents; Lung; Lung Diseases; Lymphocytosis; Male; Middle Aged; Piperidines; Positron Emission Tomography Computed Tomography; Protein Kinase Inhibitors; Radiopharmaceuticals; Registries; Retrospective Studies; Young Adult

The renin-angiotensin system (RAS), which plays an important role in the progression of heart failure, is efficiently blocked by the inhibition of renin, the rate-limiting enzyme in the RAS cascade. In the present study, we investigated the cardioprotective effects of TAK-272 (SCO-272, imarikiren), a novel, orally effective direct renin inhibitor (DRI), and compared its efficacy with that of aliskiren, a DRI that is already available in the market. TAK-272 was administered to calsequestrin transgenic (CSQ-tg) heart failure mouse model that show severe symptoms and high mortality. The CSQ-tg mice treated with 300 mg/kg, the highest dose tested, of TAK-272 showed significantly reduced plasma renin activity (PRA), cardiac hypertrophy, and lung congestion. Further, TAK-272 reduced cardiomyocyte injury accompanied by an attenuation of the increase in NADPH oxidase 4 and nitric oxide synthase 3 expressions. TAK-272 also prolonged the survival of CSQ-tg mice in a dose-dependent manner (30 mg/kg: P = 0.42, 100 mg/kg: P = 0.12, 300 mg/kg: P < 0.01). Additionally, when compared at the same dose level (300 mg/kg), TAK-272 showed strong and sustained PRA inhibition and reduced the heart weight and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, a heart failure biomarker, while aliskiren showed a significant weaker PRA inhibition and failed to demonstrate any cardioprotective effects. Our results showed that TAK-272 is an orally active and persistent renin inhibitor, which reduced the mortality of CSQ-tg mice and conferred protection against cardiac hypertrophy and injury. Thus, TAK-272 treatment could provide a new therapeutic approach for heart failure.

Topics: Amides; Animals; Benzimidazoles; Cardiovascular Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Fumarates; Heart; Heart Failure; Hypertrophy; Lung Diseases; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; Morpholines; Piperidines; Protective Agents; Random Allocation; Renin

The aim of this study is to present our institutional experience during the management of anesthesia in lung transplantation (LT) surgeries as a definitive surgical treatment option in end-stage lung diseases.. From a total of 15 patients, lung transplantation was performed as single LT (SLT) in 4 patients (n = 4) and as sequential bilateral LT (BLT) in 11 patients (n = 11). The anesthetic management included; for induction; intravenous ketamine, midazolam at doses of 2 mg/kg, 0.05 mg/kg, respectively or propofol, fentanyl at doses of 1 mg/kg, 3 mcg/kg, respectively. For maintenance, all patients received; 100% O2 and total intravenous infusion of propofol and remifentanil at doses of 0.02 mcg/kg/min and 0.1-0.25 µg/kg/min, respectively. All patients received intravenous rocuronium bromide for induction and maintenance. Hemodynamic stability was maintained with appropriate and adequate administration of vasodilators (intravenous Prostaglandin (PGI2) (0.5-1 ng/kg/min), inhaled   nitric oxide  (10-40 ppm),  dopamine (2 mcg/kg/min) and vasopressors (intravenous dobutamine (5-15 mcg/kg/min), norepinephrine (0.05-1 mcg/kg/min),ephedrine (5 to 10 mg bolus doses ) to keep mean arterial blood pressure above 50 mmHg.. Cardiopulmonary bypass (CPB) was performed in five patients who underwent sequential BLT and one SLT case. Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) was used in four cases of sequential BLT and in two cases of SLT. Neither ECMO nor CPB was performed in two BLT and in one SLT patient. One SLT patient who underwent CPB was admitted to the intensive care unit with support of intra-aortic balloon pump (IABP) and ECMO. Intraoperative death did not occur.. During SLT or BLT, management of anesthesia with propofol and remifentanil provides a stable hemodynamic and medical support. Although our experience with VA ECMO was limited, our experience shows that this support system is a valuable tool to provide hemodynamic stability for patients undergoing LT.

Topics: Adolescent; Adult; Anesthesia; Anesthetics, Intravenous; Cardiopulmonary Bypass; Extracorporeal Membrane Oxygenation; Female; Hemodynamics; Humans; Lung Diseases; Lung Transplantation; Male; Middle Aged; Piperidines; Propofol; Remifentanil; Turkey

This study was designated to estimate protective role of ETA and ETB receptor antagonist against endothelin 1 (ET-1)-induced oxidative stress in lungs and determine whether these effects are mediated by nitric oxide (NO) synthase. Experiments were performed on Wistar rats divided into the following groups: I - saline (0.9 % NaCl); II - ET-1 (3 microg/kg b.w.), III - BQ123 (1 mg/kg b.w.) + ET-1 (3 microg/kg b.w.), IV - BQ788 (3 mg/kg b.w.) + ET-1 (3 microg/kg b.w.), V - N-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg b.w.) + ET-1 (3 microg/kg b.w.). ETA and ETB receptor antagonists or L-NAME were administered 30 min before ET-1 injection. The levels of the following substances were measured in the lungs homogenates: thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), reduced glutathione (GSH) and tumor necrosis factor-alpha (TNF-alpha). The results showed that ET-1 significantly increased TBARS, H(2)O(2) (respectively: p<0.001, p<0.02) and TNF-alpha levels (p<0.02) and decreased the GSH level (p<0.01) vs.. On the other hand, prior administration of ETA receptor blocker (BQ123) significantly attenuated TBARS (p<0.01), H(2)O(2) (p<0.02), TNF-alpha (p<0.02) and increased GSH (p<0.02) levels vs. ET-1. However, prior administration of ETB receptor blocker BQ788 did not cause significant changes in the: TBARS, H(2)O(2) and TNF-alpha (p>0.05) levels, but significantly increased the GSH level and GSH/GSSG ratio (p<0.05). Administration of L-NAME significantly attenuated TBARS (p<0.001), H(2)O(2) (p<0.05), TNF-alpha (p<0.01) and increased GSH (p<0.05) levels vs. ET-1. In conclusion, we demonstrated that ET-1 induced oxidative stress in the lungs is mediated by ETA receptors. ETA receptor blockage inhibited generation of free radicals and TNF-alpha and ameliorated antioxidant properties. Moreover, generation of reactive oxygen species is mediated by NOS in the lungs.

Topics: Animals; Endothelin Receptor Antagonists; Endothelin-1; Glutathione; Hydrogen Peroxide; Lipid Peroxidation; Lung; Lung Diseases; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Oligopeptides; Oxidative Stress; Peptides, Cyclic; Piperidines; Random Allocation; Rats, Wistar; Reactive Oxygen Species; Receptor, Endothelin A; Receptor, Endothelin B; Tumor Necrosis Factor-alpha

Tofacitinib is a novel drug that inhibits the JAK-STAT signaling pathway. It has been approved for the treatment of psoriatic arthritis and it is under investigation for the treatment of psoriasis and other inflammatory disorders. We report a case of pulmonary cryptococcosis in an otherwise immunocompetent patient taking tofacitinib for psoriasis. We hypothesized that tofacitinib contributed to this infection through inhibition of cytokines required for differentiation of T cells and suppression of macrophage activation. As dermatologists begin to use this drug they should be aware of the potential for cryptococcocal infection, because delay of diagnosis may increase the risk of a life-threatening outcome.

Topics: Aged; Cryptococcosis; Humans; Lung Diseases; Male; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Pyrroles

Since the last consensus conducted by Sfar/SRLF, the use of protocol for sedation became the reference in our ICUs. Decrease in length of stay and length of mechanical ventilation with used of these protocols have been already described. We would like to investigate the economic impact associated.. Using the PMSI data, we studied retrospectively, the economic effect, one year before and one year after protocol implementation in our ICU.. The economic evaluation compared the cost of sedation but also the cost of mechanical ventilation and length of stay in ICU.. Characteristic and number of patients were equivalent during the two years. We described a significant decrease in length of mechanical ventilation (8.8 vs. 8.4; p<0.05) but not in length of stay (11.4 vs. 11.7; NS) between the two periods. We described a decrease of sedation cost of 11 412 euros and a decrease of mechanical ventilation cost of 27 360 Euros between the two years.. We confirm in this study that use of sedation protocol in ICU is associated with a clinical impact but also with an economic effect.

Topics: Adult; Aged; Clinical Protocols; Conscious Sedation; Costs and Cost Analysis; Critical Care; Databases, Factual; Female; Fentanyl; France; Humans; Hypnotics and Sedatives; Intensive Care Units; Length of Stay; Lung Diseases; Male; Midazolam; Middle Aged; Piperidines; Remifentanil; Respiration, Artificial; Retrospective Studies

Role of 2-Deoxy-D-glucose (2-DG) in reversing the Indian red scorpion (Mesobuthus tamulus concanesis Pocock, MBT) venom-induced toxicity was examined. Femoral arterial pressure, ECG and respiratory movements were recorded in urethane anesthetized rats. Plasma glucose and serum insulin levels were also estimated. Intravenous injection of 5 mg/kg MBT venom produced immediate decrease in mean arterial pressure, heart rate and respiratory frequency followed by an increase and subsequent progressive decrease. ECG pattern exhibited ischaemic changes. There was hyperinsulinemia after venom without corresponding decrease in plasma glucose. The animals died within 37 +/- 9 min and demonstrated significant increase in pulmonary water content. 2-DG pretreatment (0.5 g/kg, iv) improved the cardiopulmonary abnormalities induced by venom and the animals survived for nearly 120 min. There was no hyperinsulinemia and increased pulmonary water content in these animals. In insulin (2 IU/kg) treated rats, the MBT venom-induced cardiopulmonary abnormalities were attenuated and ECG abnormalities were reversed. The pulmonary water content in these animals exhibited a decreasing trend and the animals survived for 120 min. Repaglinide (10 microg/kg, iv) pretreatment failed to reverse the venom-induced cardiopulmonary changes including the increased pulmonary water content. The survival time was similar to venom only group. The present results reveal that 2-DG reverses the venom-induced cardiopulmonary toxicity probably by restoring insulin sensitivity.

Topics: Anesthesia; Animals; Blood Glucose; Carbamates; Cardiovascular Abnormalities; Deoxyglucose; Hyperglycemia; India; Insulin; Lung Diseases; Myocardial Ischemia; Piperidines; Pulmonary Edema; Rats; Respiration; Scorpion Venoms; Ultrasonography

We have identified a series of amino-piperidine antibacterials with a good broad spectrum potency. We report the investigation of various subunits in this series and advanced studies on compound 8. Compound 8 possesses good pharmacokinetics, broad spectrum antibacterial activity and demonstrates oral efficacy in a rat lung infection model.

Topics: Animals; Anti-Bacterial Agents; Dioxanes; Disease Models, Animal; DNA Topoisomerases, Type II; Dogs; Haplorhini; Humans; Lung Diseases; Microbial Sensitivity Tests; Naphthyridines; Piperidines; Rats; Structure-Activity Relationship; Topoisomerase II Inhibitors

Mast cells and neutrophils are key contributors to the pathophysiological inflammatory processes that underpin asthma and chronic obstructive pulmonary disease, partly through the release of noxious serine proteases, including cathepsin G (Cat G) and chymase. From this standpoint, a dual inhibitor of neutrophil Cat G and mast cell chymase could protect against these disease-related inflammatory responses.. We examined the antiinflammatory pharmacology of RWJ-355871, a dual inhibitor of Cat G and chymase, in animal models of inflammation that evince pathophysiological pathways relevant to asthma and chronic obstructive pulmonary disease to determine the therapeutic potential of this compound.. In an ovalbumin (OVA)-sensitized rat model, RWJ-355871 was administered to block the mast-cell-mediated increase in paw volume caused by OVA injection. In a sheep asthma model, antigen-induced airway responses were assessed with and without aerosol treatment with RWJ-355871. In a murine tobacco-smoke model of airway inflammation, the effect of RWJ-355871 on smoke-induced neutrophilia was determined.. Intravenous treatment of OVA-sensitized rats with RWJ-355871 provided dose-dependent reduction in the increase in rat paw volume. In allergic sheep, aerosol pretreatment with RWJ-355871 showed dose-dependent inhibition of the antigen-induced early response, late response, and post-antigen-induced airway hyperreponsiveness. In tobacco-smoke-exposed mice, nebulized RWJ-355871 significantly reduced the smoke-induced neutrophilia from the levels observed in untreated mice.. The preclinical antiinflammatory effects of RWJ-355871 in these animal models of inflammation indicate that this dual inhibitor may have therapeutic utility for treating airway inflammatory diseases involving mechanisms that depend on Cat G and/or chymase.

Topics: Animals; Biomarkers; Bronchoalveolar Lavage Fluid; Cathepsin G; Chymases; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Injections, Intravenous; Lung Diseases; Mice; Organophosphonates; Piperidines; Pulmonary Disease, Chronic Obstructive; Rats; Sheep; Treatment Outcome

Adenosine A(2A) receptor activation potently attenuates lung ischemia-reperfusion injury. This study tests the hypothesis that adenosine A(2A) receptor activation attenuates ischemia-reperfusion injury by inhibiting CD4+ T cell activation and subsequent neutrophil infiltration.. An in vivo model of lung ischemia-reperfusion injury was used. C57BL/6 mice were assigned to either sham group (left thoracotomy) or 7 study groups that underwent ischemia-reperfusion (1 hour of left hilar occlusion plus 2 hours of reperfusion). ATL313, a selective adenosine A(2A) receptor agonist, was administered 5 minutes before reperfusion with or without antibody depletion of neutrophils or CD4+ T cells. After reperfusion, the following was measured: pulmonary function using an isolated, buffer-perfused lung system, T cell infiltration by immunohistochemistry, myeloperoxidase and proinflammatory cytokine/chemokine levels in bronchoalveolar lavage fluid, lung wet/dry weight, and microvascular permeability.. ATL313 significantly improved pulmonary function and reduced edema and microvascular permeability after ischemia-reperfusion compared with control. Immunohistochemistry and myeloperoxidase content demonstrated significantly reduced infiltration of neutrophils and CD4+ T cells after ischemia-reperfusion in ATL313-treated mice. Although CD4+ T cell-depleted and neutrophil-depleted mice displayed significantly reduced lung injury, no additional protection occurred when ATL313 was administered to these mice. Expression of tumor necrosis factor-alpha, interleukin 17, KC, monocyte chemotactic protein-1, macrophage inflammatory protein-1, and RANTES were significantly reduced in neutrophil- and CD4+ T cell-depleted mice and reduced further by ATL313 only in neutrophil-depleted mice.. These results demonstrate that CD4+ T cells play a key role in mediating lung inflammation after ischemia-reperfusion. ATL313 likely exerts its protective effect largely through activation of adenosine A(2A) receptors on CD4+ T cells and neutrophils.

Topics: Adenosine A2 Receptor Agonists; Animals; Capillary Permeability; CD4-Positive T-Lymphocytes; Chemokines; Cytokines; Immunohistochemistry; Lung Diseases; Male; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; Piperidines; Reperfusion Injury; Respiratory Function Tests

Adenosine and the activation of specific adenosine receptors are implicated in the attenuation of inflammation and organ ischemia-reperfusion injury. We hypothesized that activation of A(1), A(2A), or A(3) adenosine receptors would provide protection against lung ischemia-reperfusion injury.. With the use of an isolated, ventilated, blood-perfused rabbit lung model, lungs underwent 18 hours of cold ischemia followed by 2 hours of reperfusion. Lungs were administered vehicle, adenosine, or selective A(1), A(2A), or A(3) receptor agonists (CCPA, ATL-313, or IB-MECA, respectively) alone or with their respective antagonists (DPCPX, ZM241385, or MRS1191) during reperfusion.. Compared with the vehicle-treated control group, treatment with A(1), A(2A), or A(3) agonists significantly improved function (increased lung compliance and oxygenation and decreased pulmonary artery pressure), decreased neutrophil infiltration by myeloperoxidase activity, decreased edema, and reduced tumor necrosis factor-alpha production. Adenosine treatment was also protective, but not to the level of the agonists. When each agonist was paired with its respective antagonist, all protective effects were blocked. The A(2A) agonist reduced pulmonary artery pressure and myeloperoxidase activity and increased oxygenation to a greater degree than the A(1) or A(3) agonists.. Selective activation of A(1), A(2A), or A(3) adenosine receptors provides significant protection against lung ischemia-reperfusion injury. The decreased elaboration of the potent proinflammatory cytokine tumor necrosis factor-alpha and decreased neutrophil sequestration likely contribute to the overall improvement in pulmonary function. These results provide evidence for the therapeutic potential of specific adenosine receptor agonists in lung transplant recipients.

Topics: Adenosine; Adenosine A1 Receptor Agonists; Adenosine A1 Receptor Antagonists; Adenosine A2 Receptor Agonists; Adenosine A2 Receptor Antagonists; Adenosine A3 Receptor Agonists; Adenosine A3 Receptor Antagonists; Animals; Blood Pressure; Disease Models, Animal; In Vitro Techniques; Lung; Lung Compliance; Lung Diseases; Perfusion; Peroxidase; Piperidines; Protective Agents; Pulmonary Artery; Pulmonary Edema; Rabbits; Receptor, Adenosine A1; Receptor, Adenosine A2A; Receptor, Adenosine A3; Reperfusion Injury; Tumor Necrosis Factor-alpha

Lung ischemia-reperfusion (IR) injury leads to significant morbidity and mortality which remains a major obstacle after lung transplantation. However, the role of various subset(s) of lung cell populations in the pathogenesis of lung IR injury and the mechanisms of cellular protection remain to be elucidated. In the present study, we investigated the effects of adenosine A2A receptor (A2AAR) activation on resident lung cells after IR injury using an isolated, buffer-perfused murine lung model.. To assess the protective effects of A2AAR activation, three groups of C57BL/6J mice were studied: a sham group (perfused for 2 hr with no ischemia), an IR group (1 hr ischemia + 1 hr reperfusion) and an IR+ATL313 group where ATL313, a specific A2AAR agonist, was included in the reperfusion buffer after ischemia. Lung injury parameters and pulmonary function studies were also performed after IR injury in A2AAR knockout mice, with or without ATL313 pretreatment. Lung function was assessed using a buffer-perfused isolated lung system. Lung injury was measured by assessing lung edema, vascular permeability, cytokine/chemokine activation and myeloperoxidase levels in the bronchoalveolar fluid.. After IR, lungs from C57BL/6J wild-type mice displayed significant dysfunction (increased airway resistance, pulmonary artery pressure and decreased pulmonary compliance) and significant injury (increased vascular permeability and edema). Lung injury and dysfunction after IR were significantly attenuated by ATL313 treatment. Significant induction of TNF-alpha, KC (CXCL1), MIP-2 (CXCL2) and RANTES (CCL5) occurred after IR which was also attenuated by ATL313 treatment. Lungs from A2AAR knockout mice also displayed significant dysfunction, injury and cytokine/chemokine production after IR, but ATL313 had no effect in these mice.. Specific activation of A2AARs provides potent protection against lung IR injury via attenuation of inflammation. This protection occurs in the absence of circulating blood thereby indicating a protective role of A2AAR activation on resident lung cells such as alveolar macrophages. Specific A2AAR activation may be a promising therapeutic target for the prevention or treatment of pulmonary graft dysfunction in transplant patients.

Topics: Adenosine A2 Receptor Agonists; Animals; Blood Platelets; Bronchoalveolar Lavage Fluid; Capillary Permeability; Chemokines; Cytokines; Lung; Lung Diseases; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Infiltration; Neutrophils; Peroxidase; Piperidines; Receptor, Adenosine A2A; Reperfusion Injury; Respiratory Function Tests

There is little report describing the effect of remifentanil on cardiac conduction system. We present a successful anesthetic management with remifentanil in a patient with sick sinus syndrome. A 66-year-old woman (31-kg, 121-cm) having sinoatrial (SA) block was diagnosed as having hepatic cell carcinoma, and radiofrequency ablation (RFA) was scheduled. She was also suffering from kyphosis due to the past history of tuberculous spondylitis. Preoperative examination of her respiratory function indicated a severe constrictive pulmonary disorder. Anesthesia was induced with propofol (30 mg), and maintained with sevoflurane (1-2%) and oxygen/air in combination with remifentanil (0.5 microg x kg(-1) x min(-1)). Temporary pacemaker was prepared during anesthesia. Neither remifentanil nor sevoflurane deteriorated SA block and her heart rate was well controlled. Respiratory dysfunction was not seen in the postoperative course. Our case suggests that remifentanil may be a suitable analgesic for patients with cardiac conduction abnormalities.

Topics: Aged; Anesthesia, General; Anesthetics, Intravenous; Catheter Ablation; Constriction, Pathologic; Female; Humans; Kyphosis; Liver Neoplasms; Lung Diseases; Piperidines; Remifentanil; Sinoatrial Block

Cardiopulmonary bypass has been shown to exert an inflammatory response within the lung, often resulting in postoperative pulmonary dysfunction. Several studies have shown that adenosine A(2A) receptor activation attenuates lung ischemia-reperfusion injury; however, the effect of adenosine A(2A) receptor activation on cardiopulmonary bypass-induced lung injury has not been studied. We hypothesized that specific adenosine A(2A) receptor activation by ATL313 would attenuate inflammatory lung injury after cardiopulmonary bypass.. Adult male Sprague-Dawley rats were randomly divided into 3 groups: 1) SHAM group (underwent cannulation + heparinization only); 2) CONTROL group (underwent 90 minutes of normothermic cardiopulmonary bypass with normal whole-blood priming solution; and 3) ATL group (underwent 90 minutes of normothermic cardiopulmonary bypass with ATL313 added to the normal priming solution).. There was significantly less pulmonary edema and lung injury in the ATL group compared with the CONTROL group. The ATL group had significant reductions in bronchoalveolar lavage interleukin-1, interleukin-6, interferon-gamma, and myeloperoxidase levels compared with the CONTROL group. Similarly, lung tissue interleukin-6, tumor necrosis factor-alpha, and interferon-gamma were significantly decreased in the ATL group compared with the CONTROL group. There was no significant difference between the SHAM and ATL groups in the amount of pulmonary edema, lung injury, or levels of proinflammatory cytokines.. The addition of a potent adenosine A(2A) receptor agonist to the normal priming solution before the initiation of cardiopulmonary bypass significantly protects the lung from the inflammatory effects of cardiopulmonary bypass and reduces the amount of lung injury. Adenosine A(2A) receptor agonists could represent a new therapeutic strategy for reducing the potentially devastating consequences of the inflammatory response associated with cardiopulmonary bypass.

Topics: Adenosine A2 Receptor Agonists; Animals; Blood Gas Analysis; Bronchoalveolar Lavage Fluid; Cardiopulmonary Bypass; Interferon-gamma; Interleukin-1; Interleukin-6; Lung; Lung Diseases; Male; Peroxidase; Piperidines; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Necrosis Factor-alpha

Adenosine A2A receptor activation during reperfusion improves lung ischemia-reperfusion injury. In this study we sought to determine whether pretreatment of rabbits with a potent and selective adenosine A2A receptor agonist, ATL-313, before transplantation or whether adding ATL-313 to the preservation solution results in equivalent or additional protection compared with ATL-313 added during reperfusion.. An isolated, ventilated, ex vivo blood-perfused rabbit lung model was used. All groups underwent 2 hours of reperfusion after 18 hours of cold ischemia (4 degrees C). ATL-313 was administered 1 hour before ischemia intravenously, with the preservation solution, and/or during reperfusion.. Both pretreatment of donor animals with ATL-313 or adding ATL-313 just during reperfusion improved pulmonary function, but significantly greater improvement was observed when pretreatment and treatment during reperfusion were combined (all P < .05). Myeloperoxidase levels, bronchoalveolar lavage tumor necrosis factor alpha levels, and pulmonary edema were all maximally decreased in the combined treatment group. The administration of an equimolar amount of the potent and highly selective adenosine 2A receptor antagonist, ZM 241385, along with ATL-313, resulted in the loss of protection conferred by ATL-313.. Adenosine A2A receptor activation with ATL-313 results in the greatest protection against lung ischemia-reperfusion injury when given before ischemia and during reperfusion. Improved pulmonary function observed with adenosine A2A receptor activation was correlated with decreased bronchoalveolar lavage tumor necrosis factor alpha and decreased lung myeloperoxidase. The loss of protection observed with the concurrent administration of the adenosine A2A receptor antagonist, ZM 241385, supports that the mechanism of ATL-313 protection is specifically mediated via adenosine A2A receptor activation.

Topics: Adenosine A2 Receptor Agonists; Animals; Anti-Inflammatory Agents; Female; In Vitro Techniques; Lung Diseases; Lung Transplantation; Male; Models, Animal; Piperidines; Rabbits; Receptor, Adenosine A2A; Reperfusion Injury; Tissue and Organ Harvesting

Earlier work from our laboratory has suggested a role for the neuropeptide substance P (SP) in inducing lung injury in sepsis. In that study, mice lacking the preprotachykinin-A gene, which encodes for SP, were protected against lung injury in sepsis. To further substantiate the role of SP in sepsis and to study its mechanism, we have evaluated the effect of SR140333, a SP receptor antagonist, on lung injury in sepsis, which was induced in male Swiss mice by cecal ligation and puncture (CLP). Sham-operated animals received the same surgical procedure, except CLP. Vehicle or SR140333 (1 mg/kg, s.c.) was administered to CLP mice 30 min before or 1 h after the CLP. Eight hours after surgery, lung tissue was collected and analyzed for myeloperoxidase (MPO) activity, chemokines, cytokines, and adhesion molecules. The CLP procedure alone caused a significant increase in the lung levels of MIP-2, MCP-1, IL-1beta, IL-6, ICAM-1, E- and P-selectin, and MPO activity when compared with sham-operated mice. SR140333 injected 30 min before or 1 h after CLP significantly attenuated the increased lung MPO activity and levels of MIP-2, MCP-1, IL-1beta, IL-6, ICAM-1, and E- and P-selectin compared with CLP-operated mice injected with the vehicle. Histological evaluation of the lung sections further supported the beneficial effect of SR140333 on lung inflammation. Therefore, SP receptor antagonism can be a potential therapeutic target in polymicrobial sepsis, and this effect is brought about via reduction in leukocyte recruitment.

Topics: Animals; Cecum; Chemokines; Cytokines; Enzyme-Linked Immunosorbent Assay; Lung; Lung Diseases; Lung Injury; Male; Mice; Neurokinin-1 Receptor Antagonists; Neutrophils; Peroxidase; Piperidines; Protein Precursors; Quinuclidines; Receptors, Neurokinin-1; Sepsis; Stereoisomerism; Tachykinins

To report a case of lower respiratory tract obstruction occurring in a patient with primary pulmonary amyloidosis and discuss anesthetic management.. A 53-yr-old man was referred to our institution for microlaryngoscopy and laser treatment of the larynx. He presented with a five-year history of primary laryngo-tracheo-bronchial amyloidosis and symptoms consistent with narrowing of the conducting airways. General anesthesia was induced with iv propofol 150 mg and remifentanil 50 microg. Mivacurium 20 mg provided muscle relaxation for endotracheal intubation. Following endotracheal intubation, the airway became obstructed and patient ventilation impossible. The endotracheal tube was removed and a Dedo laryngoscope inserted. Gas exchange was maintained using supraglottic jet ventilation via a distal port of the laryngoscope. Rigid bronchoscopy showed tissue partially obstructing the lumen of the lower trachea. This was removed and the airway appeared patent. At the end of the case, a further episode of lower airway obstruction occurred requiring reinsertion of the laryngoscope and resumption of jet ventilation. Extensive debridement through the bronchoscope was required before adequate ventilation could be restored. Some days later when the patient's condition deteriorated again and he required further debridement of the trachea and insertion of a tracheostomy, guide wires were positioned in the femoral vessels in the event that cardiopulmonary bypass was required for gas exchange.. Primary laryngo-tracheo-bronchial amyloidosis is a recurrent disease, requiring repetitive surgical procedures. Airway compromise can be a persistent problem. Awareness of this uncommon disease process and its presentation may serve to caution the anesthesiologist presented with this type of case.

Topics: Amyloidosis; Anesthesia, General; Anesthetics, Intravenous; Bronchial Diseases; High-Frequency Jet Ventilation; Humans; Intubation, Intratracheal; Isoquinolines; Laryngoscopy; Laryngostenosis; Lung Diseases; Male; Middle Aged; Mivacurium; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Remifentanil; Reoperation; Respiratory Tract Diseases; Tracheal Stenosis

The participation of endothelins (ETs) in a model of neutrophil-dependent lung injury induced by intrabronchial instillation of rabbit antibodies to ovalbumin followed by i.v. injection of the antigens (Arthus reaction) was investigated. Hemorrhagic lesions were evaluated by measuring the extravasations of hemoglobin in lung parenchyma. From 5 min to 24 h after the Arthus reaction (AR), endothelin (ir-ET) levels in bronchoalveolar lavage fluid (BALF) and in plasma were measured by radioimmunoassay. BALF levels of ir-ET were not different between control and AR animals for the first 90 min after the antigen challenge but increased from 2 to 24 h after induction of AR. ET levels in the plasma did not change from the respective controls over the same 24 h period. Increased ir-ET in BALF was not affected by pretreatment with L-NAME (30 mg/kg, i.v.). A PAF antagonist (BN52021; 5 and 10 mg/kg, i.v.) increased ET content in BALF and decreased the intensity of the AR. Thiorphan (2 mg/kg, i.v.) inhibited the AR-induced hemorrhagic lesions in lungs. An ET(A) receptor antagonist, BQ-123 (1 mg/kg, i.v.) potentiated, whereas the ET(B) antagonist, BQ-788 (1 mg/kg, i.v.) inhibited the lung hemorrhage. It is concluded that ETs are released during and play a role in the lung AR.

Topics: Animals; Antigen-Antibody Complex; Arthus Reaction; Bronchoalveolar Lavage Fluid; Diterpenes; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelins; Fibrinolytic Agents; Ginkgolides; Hemoglobins; Hemorrhage; Lactones; Lung Diseases; Male; Neutrophils; Oligopeptides; Ovalbumin; Peptides, Cyclic; Piperidines; Pneumonia; Rats; Rats, Wistar

To determine if a modern anesthetic approach permits extubation immediately after surgery for single-lung transplantation.. A retrospective study of all patients undergoing single-lung transplantation from June 1993 to December 1999 in Denmark.. Rigshospitalet, Copenhagen University hospital.. One hundred six consecutive patients scheduled for single-lung transplantation.. From July 1997, the anesthetic approach was changed to facilitate early extubation. The changes included epidural analgesia and short-acting anesthetic drugs.. One hundred six patients were anesthetized for single-lung transplantation. The first 33 patients were moved to the intensive care unit for postoperative mechanical ventilation. After the change of anesthesia technique, 53 of 73 patients were extubated in the operating room. Eleven patients needed reintubation within the first 24 hours because of respiratory insufficiency, pulmonary edema, hemorrhage, or pneumothorax. The need for reintubation increased the length of stay in the intensive care unit by 1 day from 2 to 3 days (NS). The possibility of early extubation or the need for reintubation was not related to age, weight, sex, preoperative condition, mode of transport of the graft, duration of graft ischemia, or side of transplantation.. This study has shown that it is possible to extubate patients in the operating room immediately after single-lung transplantation in the majority of cases.

Topics: Adult; Aged; Analgesia, Epidural; Analgesics, Opioid; Anesthetics, Combined; Female; Fentanyl; Forced Expiratory Volume; Humans; Hypnotics and Sedatives; Intubation, Intratracheal; Lung Diseases; Lung Transplantation; Male; Middle Aged; Piperidines; Propofol; Remifentanil; Retrospective Studies; Time Factors; Ventilator Weaning

The effects of a 5-hydroxytryptamine (5-HT) challenge infusion on pulmonary function values were studied in healthy calves, pretreated with varying doses of metrenperone, a selective type 2 serotonergic (5-HT2) antagonist. In the first part of the experiment, the 5-HT challenge was performed 30 minutes after administration of metrenperone at a dose of 0.025 mg kg-1 (group 1, n = 8), 0.050 mg kg-1 (group 2, n = 8) and 0.100 mg kg-1 (group 3, n = 7). In the second part, the 5-HT challenge was performed 12 hours after administration of metrenperone at a dose of 0.050 mg kg-1 (group 4, n = 5) and 0.100 mg kg-1 (group 5, n = 5). None of the three doses of metrenperone influenced the 5-HT-induced ventilatory changes. For the challenge performed 30 minutes after blockade, all three doses inhibited the bronchoconstrictive process triggered by the 5-HT challenge. There was no dose-related inhibition. On the other hand, when the challenge was performed 12 hours after metrenperone, there was a dose-related inhibition with only the higher dose (0.100 mg kg-1) showing a significant efficacy in inhibiting 5-HT-induced bronchoconstriction. It is concluded that, if 5-HT is involved in the pathophysiological processes of respiratory diseases in cattle, a 5-HT2 blockade with metrenperone at a dose rate of 0.100 mg kg-1 and with a dosage interval of 12 hours should improve pulmonary function.

Topics: Animals; Cattle; Dose-Response Relationship, Drug; Lung Diseases; Male; Piperidines; Respiration; Respiratory Function Tests; Serotonin; Serotonin Antagonists; Tidal Volume

The protective effect of three dithiocarbamates against lung tissue damage induced by a single intratracheal instillation of cadmium chloride was examined in rats. The relative efficacy of these compounds was tested by comparing characteristic features of lung tissue damage: the increase of lung weight, and the changes in the synthesis and content of structural proteins. Of three compounds administered intraperitoneally at a dose of 2.46 mmol/kg body weight, the most effective in suppressing lung damage was sodium bis(hydroxyethyl)dithiocarbamate (DEDTC). Its efficacy was dependent on the time interval between administration of cadmium chloride and the DEDTC. The parameters of lung tissue damage which were examined approached control values when DEDTC and cadmium chloride were administered simultaneously.

Topics: Animals; Cadmium; Cadmium Poisoning; Connective Tissue; Copper; Ditiocarb; Lung; Lung Diseases; Male; Organ Size; Piperidines; Poisoning; Rats; Rats, Inbred Strains; Sorbitol; Thiocarbamates; Zinc

Clinical evaluation and prolonged esophageal pH monitoring were performed before and during treatment with cisapride (0.3 mg/kg t.i.d.) for 1 month in 19 children with reflux-associated bronchopulmonary disease. Results (mean +/- SEM) show that cisapride significantly decreases the frequency of long duration (greater than 5 min) reflux episodes (from 9.7 +/- 0.7 to 5.7 +/- 1.2), the percentage of total time pH was less than 4 (from 15.9 +/- 2.5 to 7.7 +/- 1.1%), the percentage of time pH was less than 4 at night (from 18.0 +/- 3.9 to 4.9 +/- 1.5%), the duration of the longest reflux episodes (from 44.5 +/- 6.4 to 19.7 +/- 2.7 min), as well as the duration of reflux at night (from 100.1 +/- 28.0 to 28.2 +/- 10.1 min). The frequency of reflux episodes, however, remains unaffected by cisapride. Cough fits at night disappeared completely in 12 out of 13 children. We conclude that cisapride given for 1 month significantly decreased gastroesophageal reflux as well as cough episodes at night.

Topics: Bronchial Diseases; Child; Child, Preschool; Cisapride; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Lung Diseases; Male; Monitoring, Physiologic; Piperidines; Serotonin Antagonists

Topics: Antitussive Agents; Codeine; Humans; Lung Diseases; Piperidines

Topics: Antitussive Agents; Cough; Humans; Lung Diseases; Piperidines

Topics: Doxapram; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Lung Diseases; Male; Middle Aged; Piperidines; Postoperative Complications

Topics: Abdomen; Adult; Analgesics; Anesthesia, Endotracheal; Bronchitis; Female; Humans; Lung Diseases; Piperidines; Postoperative Complications; Tracheal Diseases

Topics: Bronchitis; Chronic Disease; Humans; Injections, Intravenous; Khellin; Lung Diseases; Lung Diseases, Obstructive; Phenothiazines; Piperidines; Posture; Quaternary Ammonium Compounds; Respiratory Tract Diseases; Theophylline

Topics: Adult; Aged; Expectorants; Humans; Lung Diseases; Male; Middle Aged; Piperidines

Topics: Acetazolamide; Amides; Chronic Disease; Clopamide; Diuretics; Humans; Hydrogen-Ion Concentration; Lung Diseases; Piperidines; Respiratory Insufficiency

Topics: Acetazolamide; Acid-Base Equilibrium; Acidosis, Respiratory; Amides; Bronchial Diseases; Clopamide; Diuretics; Ethacrynic Acid; Humans; Hypercapnia; Lung Diseases; Piperidines; Respiratory Insufficiency

Topics: Antitussive Agents; Humans; Lung Diseases; Piperidines

Topics: Adult; Aged; Anxiety Disorders; Biliary Tract Diseases; Cardiovascular Diseases; Depression; Dysautonomia, Familial; Female; Gastrointestinal Diseases; Humans; Hypertension; Lung Diseases; Male; Middle Aged; Neoplasms; Piperidines; Tranquilizing Agents