piperidines and Syndrome

Over the last decade, there have been important developments in the treatment of lymphoproliferative disorders. Apart from conventional chemotherapy, a wide array of therapies has been developed, with different indications. The aim of this review is to evaluate the risk of infection associated with these therapies, as well as establishing prevention recommendations. In all cases, the patient's underlying disease as well as concomitant or previous therapies have an impact on the risk of infection. Anti-CD20 antibodies (rituximab, ofatumumab and obinutuzumab) have been associated with a higher risk of bacterial and viral infection, as well as reactivation of latent infections and opportunistic infections. Alemtuzumab is associated with severe, protracted immunosuppression. Ibrutinib and acalabrutinib have been linked to bacterial infections (especially respiratory infections), invasive fungal infections and opportunistic infections. Idelalisib carries a higher risk of Pneumocystis jirovecii and infection and cytomegalovirus reactivation. Venetoclax is associated with respiratory infections and neutropenia. Immune checkpoint inhibitors are not directly associated with a higher risk of infection; nevertheless, the use of corticosteroids and immunosuppressants to control immune-related adverse events results in an increase of the risk of infection. Brentuximab, lenalidomide and histone deacetylase inhibitors do not seem to be associated with a higher risk of infections. Although data are scarce, a higher number of infections have been observed with cellular therapies, mostly in patients with more than 3 previous antineoplastic treatments or those receiving tocilizumab or corticosteroids for managing the cytokine release syndrome. In all patients, we recommend appropriate vaccination, screening for latent infections, and individualized prophylaxis recommendations.

Topics: Adenine; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents, Immunological; Benzamides; Bridged Bicyclo Compounds, Heterocyclic; Communicable Disease Control; Humans; Immune Checkpoint Inhibitors; Infections; Lymphoproliferative Disorders; Piperidines; Purines; Pyrazines; Quinazolinones; Risk; Rituximab; Sulfonamides; Syndrome

Bing-Neel syndrome (BNS) is characterised by infiltration of the central nervous system by lymphoplasmacytic lymphoma (LPL) cells and is traditionally regarded as a complication of pre-existing systemic Waldenström's macroglobulinaemia (WM). We describe the case of a 49 year old woman with leptomeningeal LPL who did not fulfil diagnostic criteria for concomitant systemic WM at presentation, and who failed to respond to conventional chemotherapy treatment (including high dose methotrexate) but did respond to the oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib. This highlights an important variation in the typical natural history of this rare disease and also further supplements emerging evidence regarding efficacy of ibrutinib in its treatment.

Topics: Adenine; Female; Humans; Lymphoma; Meningeal Carcinomatosis; Middle Aged; Piperidines; Pyrazoles; Pyrimidines; Syndrome

Ibrutinib is a tyrosine kinase inhibitor commonly used in patients with chronic lymphocytic leukemia. Based on the published literature, it has a very sound ophthalmologic safety profile. In the following, we describe a case of anterior chamber fibrinoid syndrome in a patient on ibrutinib for B-cell chronic lymphocytic leukemia after uncomplicated cataract extraction.. A 75-year-old white man with B-cell chronic lymphocytic leukemia on ibrutinib therapy and without significant past ocular history presented 1 day after uncomplicated phacoemulsification with in-the-bag intraocular lens implantation with multiple, discrete, pigmented cords in the anterior chamber. His vision was 20/100 and intraocular pressure was 43 mmHg. There was no hypopyon, hyphema, or cellular reaction. The dilated fundus examination was unremarkable. He was diagnosed as having fibrinoid syndrome and started on topical prednisolone, brimonidine, timolol-dorzolamide, and orally administered acetazolamide. Within 2 weeks, the fibrin cords disappeared completely, vision improved to 20/30, and the intraocular pressure normalized off all medications.. The precise etiology of fibrinoid syndrome remains unclear. This is the first case of fibrinoid syndrome in a patient on ibrutinib, which is known to cross the blood-brain barrier and induce intraocular changes. It is important to differentiate this syndrome from toxic anterior segment syndrome and endophthalmitis, and to initiate appropriate treatment. The fibrin bands tend to be exquisitely sensitive to topical steroids and to resolve within a few weeks without sequelae.

Topics: Adenine; Administration, Topical; Aged; Anterior Chamber; Antihypertensive Agents; Antineoplastic Agents; Brimonidine Tartrate; Cataract Extraction; Humans; Intraocular Pressure; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Phacoemulsification; Piperidines; Prednisolone; Pyrazoles; Pyrimidines; Sulfonamides; Syndrome; Thiophenes; Timolol; Treatment Outcome; Visual Acuity

Charles Bonnet syndrome (CBS) is characterized by recurrent or persistent complex visual hallucinations that occur in visually impaired individuals with intact cognition and no evidence of psychiatric illness. Patients usually retain insight into the unreal nature of their hallucinations.3,4 CBS is often misdiagnosed, and predominantly affects elderly patients with vision changes (e.g., age-related macular degeneration, glaucoma, and cataract). While many require only the assurance of the benign nature of the hallucinations, nonpharmacological and pharmacological interventions have been reported to be useful in the treatment of CBS. This case involves an 83-year-old female, with a two-year history of CBS, who presented to the clinic with worsening visual hallucinations over the past few months. She was starting to lose insight into her hallucinations secondary to her new diagnosis of dementia. Several pharmacological agents were explored to determine the most appropriate choice for our patient. Ultimately, this patient was started on donepezil (reported to be successful in a CBS case report), which helped improve her cognitive function. At future follow-up visits, her hallucinations improved and her cognitive function stabilized. Pharmacists should be aware of CBS and its treatment options to properly assist physicians in the medication-selection process to alleviate distress experienced by patients with CBS. In patients who may benefit from pharmacological treatment, physicians should weigh the risks and benefits of the different treatment options. Donepezil can be a favorable option in CBS patients with Alzheimer's type dementia.

Topics: Aged, 80 and over; Cognition; Dementia; Donepezil; Female; Hallucinations; Humans; Indans; Nootropic Agents; Piperidines; Syndrome; Treatment Outcome; Vision Disorders

Topics: Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Cohort Studies; Donepezil; Dystonia; Galantamine; Humans; Indans; Male; Piperidines; Syndrome

Mild cognitive impairment (MCI) is a clinical syndrome thought to represent the transition between normal function and dementia. This review describes data that support the existence of such a transitional phase, outlines the heterogeneity of MCI and how that has influenced the evolving concept of MCI, and discusses the impact of heterogeneity on recent MCI clinical trials.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Clinical Trials as Topic; Cognition Disorders; Dementia; Donepezil; Humans; Indans; Models, Psychological; Neuropsychological Tests; Piperidines; Syndrome; Terminology as Topic; Treatment Outcome

Topics: Amnesia; Cholinesterase Inhibitors; Diagnostic and Statistical Manual of Mental Disorders; Donepezil; Humans; Indans; Piperidines; Syndrome; Thiamine

Platelet membrane glycoprotein IIb/IIIa inhibitors, a new class of potent antiplatelet agents, have been used in the treatment of acute coronary syndromes as well as in the prevention of complications after percutaneous coronary interventions. Approximately 50,000 patients with coronary artery disease have been enrolled in randomized studies of glycoprotein IIb/IIIa inhibitors. The purpose of this article is to review the pharmacology of glycoprotein IIb/IIIa inhibitors, the results of the clinical trials using these agents, and their current use in percutaneous coronary interventions and the treatment of acute coronary syndromes.

Topics: Abciximab; Acetates; Acute Disease; Administration, Oral; Alanine; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Benzamidines; Coronary Disease; Eptifibatide; Hemorrhage; Humans; Immunoglobulin Fab Fragments; Myocardial Infarction; Oximes; Peptides; Piperidines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyrrolidines; Randomized Controlled Trials as Topic; Stents; Syndrome; Thrombocytopenia; Thrombolytic Therapy; Tirofiban; Tyrosine

Platelet aggregation plays a central role in the pathogenesis of thrombosis and the acute coronary syndromes. When given intravenously, potent selective antagonists of fibrinogen binding to the glycoprotein (GP) IIb/IIIa receptor, the final common pathway for platelet aggregation, have been effective in the treatment of acute coronary syndromes. Their benefit ceases, however, with the end of the infusion. Aspirin reduces the incidence of secondary vascular events by 25% to 30% after an acute coronary syndrome, and clopidogrel provides modest improvement over aspirin. However, both are relatively weak antiplatelet agents that each block only one of many pathways to platelet activation and surface membrane expression of the competent GP IIb/IIIa receptor. With the success of the intravenous GP IIb/IIIa antagonists in the acute setting, recent interest has focused on the potential benefit of oral GP IIb/IIIa antagonists used long-term for secondary prevention. The oral agents tested in phase III studies thus far have not performed up to expectations, however. The following paper reviews these studies and the implications of their results.

Topics: Alanine; Angina, Unstable; Aspirin; Benzamidines; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Myocardial Infarction; Oximes; Piperidines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyrrolidines; Syndrome; Treatment Outcome

Insulin resistance is an early and major feature in the development of non-insulin-dependent diabetes mellitus(NIDDM). It is also associated with hyperlipidemia, hypertension, obesity and cardiovascular disease. It is the clustor of the risk factors for atherosclerosis and recognized as 'insulin-resistance syndrome' (Syndrome X). Central (abdominal) obesity is much more strongly associated with insulin resistance than overall obesity. The increase of both the influx of free fatty acid to liver and the production of TNF-alpha in adipose tissue may play an important role in mechanism of insulin resistance associated with central obesity. Calorie restriction and weight loss improve insulin sensitivity in overweight humans. Exercise training also improves insulin sensitivity via increased oxidative enzymes, glucose transporters (GLUT4) and capillarity in muscle as well as by reducing abdominal fat. The new 'glitazones' (thiazolidinediones) is used clinically to improve insulin sensitivity.

Topics: Fatty Acids, Nonesterified; Humans; Insulin Resistance; Obesity; Piperidines; Syndrome

Topics: Antacids; Anti-Ulcer Agents; Cisapride; Diagnosis, Differential; Dopamine Antagonists; Dyspepsia; Histamine H2 Antagonists; Humans; Middle Aged; Piperidines; Serotonin Antagonists; Syndrome; Terminology as Topic

Negative symptoms in schizophrenia comprise a psychopathologic and pathophysiologic syndrome which is absent from normal mental function. Renewed interest in negative symptoms has led to the development of better measuring instruments, among which is the Positive And Negative Syndrome Scale (PANSS), which provides a way of measuring and reporting positive and negative symptoms in a balanced and convenient form. A number of strategies are being investigated for treating negative symptoms. Dopamine agonists such as levodopa, amphetamines and bromocriptine have been shown to produce improvements in negative symptoms, although good, well-controlled clinical trials are lacking. Partial dopamine agonists, such as MAR 327, are also currently under investigation and results are expected soon. Tricyclic, selective serotonin reuptake inhibitors and monoamine oxidase antidepressants appear to be able to modify negative symptoms in schizophrenia, although, once again, carefully designed trials are needed. Modification of GABAergic transmission has shown little promise, but the use of glycine to augment transmission at N-methyl-D-aspartate (NMDA) synapses suggests that the strategy may be beneficial. These results also imply that altered glutamate receptor function may be partly responsible for negative symptoms. One strategy that has been shown to have a beneficial effect against negative symptoms is combined serotonin/dopamine antagonism. Clozapine was found to have this profile after its introduction, and the recently introduced antipsychotic, risperidone was developed intentionally to be a combined 5-HT2/D2 antagonist. Both risperidone and clozapine have been shown to be effective against negative symptoms. One problem associated with the assessment of drug effects on negative symptoms, however, is that drugs can act on both primary and secondary negative symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Affective Symptoms; Antipsychotic Agents; Clozapine; Humans; Isoxazoles; Piperidines; Psychiatric Status Rating Scales; Psychometrics; Risperidone; Schizophrenia; Schizophrenic Psychology; Syndrome

At the end of the last century, Hughlings-Jackson suggested that positive and negative syndromes should be kept apart in psychotic disorders. When the concepts of dementia praecox and schizophrenia were introduced by Kraepelin and Bleuler, emphasis was laid on the negative symptoms, regarded as fundamental. After the introduction of the "first rank symptoms" by Schneider emphasis switched to the positive symptoms in schizophrenia and these symptoms were included in most diagnostic criteria. In the 1980s Andreasen and Crow suggested a dichotomy into positive and negative syndromes in schizophrenia. Kay and co-workers introduced a Positive And Negative Syndrome Scale (PANSS) for schizophrenia. In the original studies satisfactory construct validity and inter-rater reliability were demonstrated. However, in studies outside the USA a high construct validity was found for the negative scales but not for the positive and general psychopathology scales. Furthermore, the inter-rater reliability of the negative scale was a problem. After introduction of the Structured Clinical Interview for the PANSS (SCI-PANSS) the inter-rater reliability increased for all three scales. In an early study Kay and Sevy found seven factors in a principal component analysis of the PANSS and suggested a four factor pyramidical model. Later principal component analyses by Lepine, Peralta et al. and Kawasaki et al. suggested that the four factor model was an oversimplification and Lindström and von Knorring suggested a five factor pyramidical model. A similar model was later suggested by Bell et al. after a reanalysis of the original series of Kay and Sevy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Affective Symptoms; Antipsychotic Agents; Humans; Isoxazoles; Piperidines; Psychiatric Status Rating Scales; Psychometrics; Reproducibility of Results; Risperidone; Schizophrenia; Schizophrenic Psychology; Syndrome

We present 2 new patients with the megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), review the literature, and discuss the prenatal diagnosis and treatment. MMIHS, as reported in 43 cases, is usually lethal. Most children die during the first year of life, and only 3 children survived their first year. We report the 6th pair of sibs with the disease. Overall, 17 patients reported have had sibs with MMIHS or the parents were consanguineous; 4 times the parents were first, cousins, confirming that this is an autosomal recessive disorder. The present 2 children, whose parents also were first cousins, were of different sex. They had typical MMIHS with abdominal distension due to pronounced megacystis, hydronephrosis, microcolon, and microileum, involving the distal part of the ileum, malrotation of the gut, and intestinal hypoperistalsis. Neither surgery nor medical treatment was successful and the children died at the age of 19 days and 2 1/2 months, respectively. There is no cure for the disease. However, a new protkinetic drug, Cisapride might be worth trying in these cases. Prenatal ultrasound diagnosis of MMIHS might be possible.

Topics: Abnormalities, Multiple; Cisapride; Colon; Consanguinity; Female; Genes, Lethal; Genes, Recessive; Humans; Ileum; Infant, Newborn; Male; Peristalsis; Piperidines; Syndrome; Urinary Bladder

Topics: Adult; Benzilates; Benzoates; Colonic Diseases, Functional; Cyclohexanecarboxylic Acids; Cyclohexanes; Diarrhea; Diethylamines; Female; Gastrointestinal Motility; Humans; Male; Middle Aged; Parasympatholytics; Phenethylamines; Piperidines; Scopolamine; Scopolamine Derivatives; Spasm; Syndrome

The use of remifentanil is often associated with the observation of mesenteric traction syndrome (MTS) soon after manipulation of the intestine during abdominal surgery. MTS symptoms include facial flushing, hypotension, and tachycardia. In the study reported here, we prospectively investigated the effects of remifentanil on the incidence of MTS in abdominal surgery.. One hundred patients scheduled for abdominal surgery were randomly assigned to two groups. In one group (n = 50), fentanyl alone was used as intravenous analgesic (control, group C); in the second group (n = 50), both fentanyl and remifentanil were used (remifentanil group, group R). In all patients, anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane inhalation. Remifentanil was continuously infused for patients in group R as an analgesic. Plasma concentration of 6-keto-PGF(1α) was measured before surgery and 20 min after the skin incision was made in six patients of group R and seven patients of group C.. MTS occurred in 20 cases in group R (40.0%), but in only five cases in group C (10.0%). In both groups, the incidence of MTS was higher in laparotomy than in laparoscopic surgery. The plasma concentration of 6-keto-PGF(1α) was low in both groups before surgery and was elevated 20 min after skin incision in both groups in patients in whom MTS appeared.. The results of this study suggest that the use of remifentanil in laparotomy facilitates MTS.

Topics: 6-Ketoprostaglandin F1 alpha; Abdomen; Aged; Anesthesia Recovery Period; Anesthesia, General; Anesthetics, Intravenous; Flushing; Hemodynamics; Humans; Hypotension; Intraoperative Complications; Laparotomy; Mesentery; Middle Aged; Piperidines; Prospective Studies; Remifentanil; Splanchnic Circulation; Syndrome; Tachycardia

We studied stent thrombosis in 4,607 patients with acute coronary syndromes who received a coronary stent as part of routine care during 2 trials of aspirin versus sibrafiban for secondary prevention. In these patients, stent thrombosis occurred more often than in previous patients who underwent elective percutaneous coronary intervention. These patients and their outcomes may be more representative of patients with typical acute coronary syndromes undergoing stenting in clinical practice.

Topics: Acute Disease; Aspirin; Causality; Coronary Disease; Coronary Thrombosis; Female; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Oximes; Piperidines; Platelet Aggregation Inhibitors; Postoperative Complications; Stents; Syndrome

Sibrafiban is a double prodrug that is converted to the inactive single prodrug and to the active IIb/IIIa antagonist following oral administration. Pharmacokinetics (PK) and pharmacodynamics (PD) of oral sibrafiban and its metabolites were evaluated in patients postacute coronary syndrome receiving once- or twice-daily sibrafiban for up to 28 days at several dose levels. Mean peak concentrations of sibrafiban were < 5 ng/mL. Peak single prodrug concentrations occurred 1.7 +/- 1.0 (mean +/- SD) hours after sibrafiban dosing. Total apparent plasma clearance of the single prodrug was 40 +/- 15 L/h, and the elimination half-life was 2.3 +/- 0.8 hours. Mean values of the steady-state pharmacokinetics for total concentrations of the active drug over all doses were: time to peak plasma concentration, 5.0 +/- 1.7 hours; apparent clearance, 13.9 +/- 3.9 L/h; and half-life, 11.0 +/- 2.8 hours. Once-daily dosing resulted in high peak-trough excursions in active drug concentrations: trough concentrations were 21% +/- 6% of peak. Twice-daily dosing resulted in an AUC for the active drug on Day 28 that was 168% +/- 36% of that on Day 1, and steady-state trough concentrations were 54% +/- 10% of peak with sustained inhibition of platelet aggregation. Dose-adjusted steady-state active drug concentrations increased with increasing age and with decreasing renal function and body weight.

Topics: Acute Disease; Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Amidines; Area Under Curve; Body Weight; Coronary Disease; Double-Blind Method; Female; Glomerular Filtration Rate; Heterocyclic Compounds; Humans; Male; Metabolic Clearance Rate; Middle Aged; Oximes; Piperidines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prodrugs; Syndrome

Negative symptoms in schizophrenia comprise a psychopathologic and pathophysiologic syndrome which is absent from normal mental function. Renewed interest in negative symptoms has led to the development of better measuring instruments, among which is the Positive And Negative Syndrome Scale (PANSS), which provides a way of measuring and reporting positive and negative symptoms in a balanced and convenient form. A number of strategies are being investigated for treating negative symptoms. Dopamine agonists such as levodopa, amphetamines and bromocriptine have been shown to produce improvements in negative symptoms, although good, well-controlled clinical trials are lacking. Partial dopamine agonists, such as MAR 327, are also currently under investigation and results are expected soon. Tricyclic, selective serotonin reuptake inhibitors and monoamine oxidase antidepressants appear to be able to modify negative symptoms in schizophrenia, although, once again, carefully designed trials are needed. Modification of GABAergic transmission has shown little promise, but the use of glycine to augment transmission at N-methyl-D-aspartate (NMDA) synapses suggests that the strategy may be beneficial. These results also imply that altered glutamate receptor function may be partly responsible for negative symptoms. One strategy that has been shown to have a beneficial effect against negative symptoms is combined serotonin/dopamine antagonism. Clozapine was found to have this profile after its introduction, and the recently introduced antipsychotic, risperidone was developed intentionally to be a combined 5-HT2/D2 antagonist. Both risperidone and clozapine have been shown to be effective against negative symptoms. One problem associated with the assessment of drug effects on negative symptoms, however, is that drugs can act on both primary and secondary negative symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Affective Symptoms; Antipsychotic Agents; Clozapine; Humans; Isoxazoles; Piperidines; Psychiatric Status Rating Scales; Psychometrics; Risperidone; Schizophrenia; Schizophrenic Psychology; Syndrome

In a double-blind, placebo-controlled, crossover trial, we investigated the effects of the prokinetic drug cisapride in patients with cystic fibrosis and chronic recurrent distal intestinal obstruction syndrome (DIOS). After a baseline period, 17 patients (12.9 to 34.9 years; 12 boys) received, in random order, cisapride (7.5 to 10 mg) and placebo three times daily by mouth, each for 6 months. Gastrointestinal symptoms (flatulence, abdominal pain, fullness, abdominal distension, nausea, anorexia, heartburn, diarrhea, vomiting and regurgitation) were scored three times monthly and physical examinations assessed. At baseline and at each 6-month period, assessment included food intake for 7 days, 3-day stool collection, pulmonary function tests, and abdominal radiographs. During cisapride therapy compared with placebo, there were significant reductions in flatulence (p less than 0.005), fullness, and nausea (p less than 0.05). Patients with the worst symptom scores benefited most from cisapride. With cisapride, 12 patients felt better and three worse (p less than 0.05); physicians judged 11 patients improved and two worse (p less than 0.05). No side effects were noted. There were no significant differences between cisapride and placebo periods in nutritional status, x-ray scores, pulmonary function, food intake (fat, protein, calories), stool size and consistency, and fecal losses of fat, bile acids, chymotrypsin, and calories. For acute episodes of DIOS, intestinal lavage was needed 6 times in 4 patients during treatment with cisapride, and 11 times in 6 patients receiving placebo. In comparison with unselected patients with cystic fibrosis and pancreatic insufficiency who were receiving enzyme supplements and who had no distal intestinal obstruction, fecal fat losses (percentage of intake) were almost twice as high in the study group with DIOS (31.2 +/- 20.6% vs 16.2 +/- 17.6%; p less than 0.01). We conclude that in the dosage used, long-term treatment with cisapride appears to improve chronic abdominal symptoms in patients with cystic fibrosis and DIOS, but fails to abolish the need for intestinal lavage. Cisapride treatment had no effect on digestion and nutritional status of cystic fibrosis patients with pancreatic insufficiency.

Topics: Adolescent; Adult; Chronic Disease; Cisapride; Cystic Fibrosis; Double-Blind Method; Female; Humans; Intestinal Obstruction; Male; Piperidines; Recurrence; Serotonin Antagonists; Syndrome

The results of evaluating the therapeutic efficacy of the new psychotropic drugs adepren, didepil, anq tempalgin made by the "Farmakhim" plant (the People's Republic of Bulgaria) are presented. Clinical trials revealed new facts that allowed to expand the scope of the indications for use formulated in the "Farmakhim" recommendations. It was found that Adepren could be used with success (in addition to the indications suggested by "Farmakhim") in the treatment of patients with depressive-paranoid paroxysms of periodic schizophrenia taking its course in the presence of general depression, as well as patients with somatogenic lingering astheno-depressive states. The therapeutic efficacy of didepil (an antiepileptic) was found to be in a direct relationship with the disease duration, character of the attacks, presence or absence of epileptic chandes of personality. The effect was the best in cases of a short duration of the disease and absence of gross epileptic personality changes, when the paroxysmal disorders were confined mostly to grand mals. A new scheme for arresting the epileptic status with didepil solution is offered. For the first time the efficacy of tempalgin in the treatment of patients suffering from alcoholic abstinence syndrome was substantiated. Optimal doses of the drugs have been determined with regard to the disease nosology and the leading syndrome. Contraindications to the use of the drugs have also been formulated.

Topics: Adolescent; Adult; Aminopyrine; Aminoquinolines; Child; Clinical Trials as Topic; Depression; Dipyrone; Drug Combinations; Epilepsy; Female; Humans; Male; Mental Disorders; Middle Aged; Phenobarbital; Piperidines; Piperidones; Procyclidine; Psychotropic Drugs; Pyrrolidines; Substance Withdrawal Syndrome; Syndrome

Topics: Adolescent; Anemia; Benzimidazoles; Cyanosis; Exanthema; Humans; Male; Piperidines; Syndrome; Urticaria

Topics: Adenine; Aged; Brain Diseases; Central Nervous System Neoplasms; Female; Humans; Immunotherapy; Piperidines; Syndrome

NOTCH1 mutations in chronic lymphocytic leukemia (CLL) lead to accumulation of NOTCH1 intracellular domain (NICD) and prolong signaling. These mutations associate with a more aggressive disease compared to wild-type (WT) CLL. In this work we demonstrate a bidirectional functional relationship between NOTCH1 and the B cell receptor (BCR) pathways. By using highly homogeneous cohorts of primary CLL cells, activation of NOTCH1 is shown to increase expression of surface IgM, as well as LYN, BTK, and BLNK, ultimately enhancing BCR signaling responses, including global mRNA translation. Upon BCR cross-linking, NOTCH1 itself is actively translated and increased on cell surface. Furthermore, BCR ligation induces calcium mobilization that can facilitate ligand-independent NOTCH1 activation. These data suggest that the two pathways are functionally linked, providing a rationale for dual inhibition strategies. Consistently, addition of the γ-secretase inhibitor DAPT to ibrutinib significantly potentiates its effects, both in vitro and in a short-term patient-derived xenograft model. While this observation may find limited applications in the CLL field, it is more relevant for Richter's Syndrome (RS) management, where very few successful therapeutic options exist. Treatment of RS-patient-derived xenografts (RS-PDX) with the combination of ibrutinib and DAPT decreases disease burden and increases overall survival.

Topics: Adenine; Adult; Aged; Aged, 80 and over; Amyloid Precursor Protein Secretases; Animals; Calcium; Diamines; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mice; Mice, Inbred NOD; Mice, SCID; Middle Aged; Piperidines; Pyrazoles; Pyrimidines; Receptor, Notch1; Receptors, Antigen, B-Cell; Signal Transduction; Syndrome; Thiazoles

Topics: Adenine; Adolescent; Agammaglobulinaemia Tyrosine Kinase; Female; Humans; Myeloid Differentiation Factor 88; Piperidines; Syndrome; Waldenstrom Macroglobulinemia

The treatment of patients with Bing-Neel syndrome (BNS) is not standardized. We included patients with Waldenström macroglobulinemia (WM) and a radiologic and/or cytologic diagnosis of BNS treated with ibrutinib monotherapy. Response assessment was based on criteria for BNS from the 8th International Workshop for WM. Survival from BNS diagnosis (BNS survival), survival from ibrutinib initiation to last follow-up or death (ibrutinib survival), and time from ibrutinib initiation to ibrutinib discontinuation for toxicity, progression, or death (event-free survival [EFS]) were estimated. Twenty-eight patients were included in our study. The median age at BNS diagnosis was 65 years. Ibrutinib was the first line of treatment for BNS in 39% of patients. Ibrutinib was administered orally at a dose of 560 and 420 mg once daily in 46% and 54% of patients, respectively; symptomatic and radiologic improvements were seen in 85% and 60% of patients within 3 months of therapy. At best response, 85% of patients had improvement or resolution of BNS symptoms, 83% had improvement or resolution of radiologic abnormalities, and 47% had cleared the disease in the cerebrospinal fluid. The 2-year EFS rate with ibrutinib was 80% (95% confidence interval [CI], 58%-91%), the 2-year ibrutinib survival rate was 81% (95% CI, 49%-94%), and the 5-year BNS survival rate was 86% (95% CI, 63%-95%). Ibrutinib therapy is effective in patients with BNS and should be considered as a treatment option in these patients.

Topics: Adenine; Adult; Aged; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Piperidines; Pyrazoles; Pyrimidines; Syndrome; Treatment Outcome; Waldenstrom Macroglobulinemia

Bing-Neel syndrome is a rare complication of Waldenström macroglobulinemia, characterized by infiltration of lymphoplasmacytic cells to the central nervous system. Multiple treatment modalities exist including purine analogs, bendamustine, high-dose methotrexate, or high-dose cytarabine. Of interest, ibrutinib, a Bruton tyrosine kinase inhibitor has also displayed efficacy in Bing-Neel syndrome. Current literature is limited for the treatment of Bing-Neel syndrome considering its rarity, and while ibrutinib is indicated for the treatment of Waldenström macroglobulinemia, it is utilized off-label for treatment of Bing-Neel syndrome. Additionally, debate exists regarding the recommended dosing strategy for ibrutinib for this indication with disease remission demonstrated at 560 mg and 420 mg. We present a case report that provides additional evidence for this debate with a patient who received 560 mg of ibrutinib initially and maintained disease control despite a dose reduction to 420 mg for tolerability. Ultimately, more data are needed to develop standardized Bing-Neel syndrome treatment strategies with specific consideration to the use of ibrutinib in this condition.

Topics: Adenine; Brain Diseases; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Syndrome; Treatment Outcome; Waldenstrom Macroglobulinemia

Waldenstrom's macroglobulinaemia (WM) is a lymphoproliferative disorder of the B cell origin. It is characterised by the presence of IgM paraprotein in the serum and lymphoplasmacytic lymphoma cells in the bone marrow with extranodal involvement relatively uncommon. Bing-Neel syndrome (BNS) is a neurological complication of WM that results from infiltration of the central nervous system by malignant lymphoplasmacytic cells. We present an interesting case of BNS that responded remarkably to ibrutinib monotherapy.

Topics: Adenine; Brain; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Mutation; Myeloid Differentiation Factor 88; Neurodegenerative Diseases; Piperidines; Pyrazoles; Pyrimidines; Syndrome; Waldenstrom Macroglobulinemia

Topics: Adenine; Drug Resistance, Neoplasm; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Piperidines; Pyrazoles; Pyrimidines; Syndrome

Topics: Adenine; Aged; Brain; Brain Diseases; Humans; Magnetic Resonance Imaging; Male; Piperidines; Pyrazoles; Pyrimidines; Syndrome; Treatment Outcome; Waldenstrom Macroglobulinemia

Richter syndrome (RS) is a rare event in chronic lymphocytic leukemia (CLL) that is influenced by biological factors and prior CLL treatments. Ibrutinib is a Bruton tyrosine kinase inhibitor that has shown remarkable efficacy in CLL; however, little is known about its relationship to RS. We report a case of ibrutinib efficacy against CLL in a patient with prolonged remission of RS.. The patient was diagnosed with CLL in 2003. Biological findings at onset included absent ZAP70 expression, mutated IGVH, and NOTCH1 mutation. He was treated with FCR with partial response. In 2013, he progressed to RS, not clonally related to the underlying CLL. The patient was treated with anthracycline- and platinum-based regimens, obtaining a complete remission. After 3 years, he presented a CLL progression with worsening lymphocytosis, anemia, thrombocytopenia, increased splenomegaly, and lymphadenopathies. Positron emission tomography-computed tomography scan excluded pathologic uptake. Thus, he was started on ibrutinib.. At 12 months' follow-up, we observed white blood cell normalization, increased hemoglobin and platelet levels, disappearance of lymphadenopathy, and spleen size reduction. Therapy was well-tolerated with no evidence of RS.. This case demonstrates sustained RS remission in a patient with CLL under ibrutinib therapy, thus improving our knowledge on the use of this new drug in CLL and beyond.

Topics: Adenine; Aged; Cell Transformation, Neoplastic; Disease Progression; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Neoplasm Recurrence, Local; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Remission Induction; Syndrome

Topics: Adenine; Animals; Antibodies; Antigens, CD19; Cytokines; Heterografts; Humans; Lymphoma, B-Cell; Mice; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Receptors, Antigen, T-Cell; Recombinant Fusion Proteins; Syndrome

Topics: Aged; Anticoagulants; Azetidines; Drug Interactions; Hemorrhage; Humans; Male; Piperidines; Pyrazoles; Pyridones; Syndrome

Topics: Adenine; Aged; Amiodarone; Atrial Fibrillation; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Heart Failure; Humans; Male; Piperidines; Pyrazoles; Pyrimidines; Syndrome

Topics: Adenine; Aged; Central Nervous System Diseases; Female; Humans; Immunoglobulin M; Leukocyte Count; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines; Syndrome; Treatment Outcome; Waldenstrom Macroglobulinemia

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Piperidines; Prednisone; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines; Rituximab; Syndrome; Vincristine

Pisa syndrome or pleurothotonus is the persistent flexion of the body and head to one side giving the appearance of the leaning tower of Pisa. It is most commonly caused by typical and atypical antipsychotic drugs. We report a case of Pisa Syndrome caused by prolonged use of high dose cholinesterase inhibitor, rivastigmine. Symptoms subsided when rivastigmine was withdrawn and did not reappear when a different cholinesterase inhibitor, donepezil was introduced. Physicians should be aware of Pisa syndrome and should alert patient of this possibility when starting and stepping up medications. The purpose of reporting this case is to create awareness among general practitioners as it is a reversible condition which responds to removal of the offending drug.

Topics: Aged; Benzodiazepines; Cholinesterase Inhibitors; Delusions; Dementia; Donepezil; Humans; Indans; Male; Movement Disorders; Olanzapine; Phenylcarbamates; Piperidines; Posture; Rivastigmine; Syndrome

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Drug Therapy, Combination; Humans; Male; Olfactory Perception; Piperazines; Piperidines; Schizophrenia, Paranoid; Syndrome

Topics: Aged; Cholinesterase Inhibitors; Donepezil; Dyskinesia, Drug-Induced; Female; Humans; Indans; Lewy Body Disease; Piperidines; Syndrome

Moderate therapeutic hypothermia is often used in aneurysm surgery and is therefore a technique anesthesiologists are familiar with. We report the case of a patient who had entered into a coma after cardiac arrest in the postanesthetic recovery unit during central venous catheterization; the patient required 35 minutes of advanced cardiopulmonary resuscitation before heart rhythm and tissue perfusion were restored. The protocol for treating post-cardiac arrest syndrome included therapeutic hypothermia, which was maintained for 12 hours. The patient was extubated after 2 days, with no neurologic deficit. Post-cardiac arrest syndrome is associated with multiple biochemical reactions which are attenuated by hypothermia. Currently available evidence does not allow definitive recommendations regarding the different techniques for inducing therapeutic hypothermia, the ideal temperature to maintain, the duration, or the rewarming process. Further studies are required.

Topics: Aged; Anesthesia, General; Anesthetics, Intravenous; Decision Trees; Heart Arrest; Humans; Hypothermia, Induced; Male; Piperidines; Remifentanil; Syndrome

Topics: Carcinoma, Neuroendocrine; Contraindications; Humans; Multiple Endocrine Neoplasia; Mutation; Piperidines; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-ret; Quinazolines; Research; Syndrome; Thyroid Neoplasms

Topics: Abnormalities, Multiple; Androstanols; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Desflurane; Facies; Female; Humans; Infant, Newborn; Intubation, Gastrointestinal; Intubation, Intratracheal; Isoflurane; Neuromuscular Nondepolarizing Agents; Piperidines; Prenatal Diagnosis; Propofol; Remifentanil; Rocuronium; Stomach; Syndrome

The term neurological diseases includes a lot of disorders concerning both the central and peripheral nervous system. Low incidence on the one hand and anaesthetic relevance on the other hand requires special attention in preoperative preparing and management of general anaesthesia. The following paper presents special problems of neurodegenerative disorders, which anaesthetic relevance is of growing interest in the changed elderly population.

Topics: Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Autonomic Nervous System; Brain; Bromocriptine; Dopamine Agonists; Humans; Intubation; Levodopa; Monoamine Oxidase Inhibitors; Muscle Relaxants, Central; Nervous System Diseases; Neurodegenerative Diseases; Neurosurgery; Parkinson Disease; Piperidines; Premedication; Preoperative Care; Propofol; Remifentanil; Selegiline; Stereotaxic Techniques; Syndrome

Stickler's syndrome is an autosomal multisystem disorder accompanying characteristic midface hypoplasia, retromicrognathia, and cleft palate. Mandibular hypoplasia causes difficulties in mask ventilation and endotracheal intubation, especially in infants. A 7-month-old girl diagnosed as Stickler's syndrome was scheduled for the laparoscopic inguinal hernia repair. However, during the direct laryngoscopy for endotracheal intubation, neither the vocal cords nor the epiglottis were visualized. At fifth intubation attempts, the part of the vocal cords was barely visualized, and the tracheal intubation was finaly successful. Anesthesia was maintained with sevoflurane and remifentanil. The patient had an uneventful recovery and was discharged on the second postoperative day without any complications. Sevoflurane and remifentanil allow faster recovery from anesthesia and both have been recommended for patients with difficult tracheal intubation in a patient such as with Stickler's syndrome.

Topics: Anesthesia; Cleft Palate; Face; Female; Hernia, Inguinal; Humans; Infant; Intubation, Intratracheal; Laparoscopy; Laryngoscopy; Methyl Ethers; Mouth Abnormalities; Piperidines; Remifentanil; Sevoflurane; Syndrome

Topics: Abnormalities, Multiple; Administration, Intranasal; Administration, Topical; Anesthetics, Local; Conjunctiva; Deep Sedation; Eye Injuries, Penetrating; Heart Defects, Congenital; Humans; Infant; Lidocaine; Limb Deformities, Congenital; Male; Midazolam; Piperidines; Remifentanil; Spinal Dysraphism; Syndrome

Topics: Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Bupivacaine; Child, Preschool; Cochlear Implantation; Fentanyl; Growth Disorders; Humans; Intellectual Disability; Laryngeal Masks; Male; Methyl Ethers; Microcephaly; Pacemaker, Artificial; Piperidines; Piroxicam; Remifentanil; Sevoflurane; Syndrome

Topics: Abnormalities, Multiple; Bone and Bones; Child; Conscious Sedation; Dwarfism; Face; Foot Deformities; Humans; Hypnotics and Sedatives; Laryngoscopy; Male; Neck; Piperidines; Remifentanil; Syndrome

Topics: Airway Obstruction; Anesthetics, Inhalation; Anesthetics, Intravenous; Failure to Thrive; Fiber Optic Technology; Glaucoma; Humans; Infant; Intellectual Disability; Intubation, Intratracheal; Laryngeal Masks; Male; Maxillofacial Abnormalities; Methyl Ethers; Monitoring, Physiologic; Piperidines; Rare Diseases; Remifentanil; Sevoflurane; Syndrome

Freeman-Sheldon syndrome, or distal arthrogryposis type 2A, is a rare congenital myopathy and dysplasia characterised by multiple contractures, abnormalities of the head and face, defective development of the hands and feet and skeletal malformations. The facial muscle contracture produces the typical 'whistling face' appearance. Anaesthetic issues include difficult intravenous access, difficult airway and postoperative pulmonary complications. Although an association with malignant hyperthermia has been suggested, this has not been confirmed. We report the management of a seven-year-old girl with Freeman-Sheldon syndrome undergoing anterior and posterior spinal surgery and describe a successful anaesthetic regimen based on a total intravenous anaesthesia technique with remifentanil and propofol without neuromuscular blocking agents. The child had an uneventful anaesthetic and postoperative course. We believe the presence of the myopathy warranted the use of a 'non-triggering' anaesthetic, as suxamethonium and volatile agents may be associated with significant complications such as muscle rigidity and rhabdomyolysis in myopathic patients, even in the absence of malignant hyperthermia.

Topics: Abnormalities, Multiple; Anesthesia, General; Anesthetics, Intravenous; Arthrogryposis; Blood Pressure; Child; Craniofacial Abnormalities; Electroencephalography; Female; Heart Rate; Humans; Monitoring, Intraoperative; Orthopedic Procedures; Pain, Postoperative; Piperidines; Propofol; Remifentanil; Respiration, Artificial; Scoliosis; Spine; Syndrome

Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Humans; Indans; Intraoperative Complications; Iris Diseases; Male; Phacoemulsification; Piperidines; Syndrome

Patient-controlled analgesia (PCA) using intravenous opioids is increasing in popularity for children aged 5 years and over. To our knowledge there are no reports on the use of PCA in children with remifentanil in the postoperative period. We report successful use of remifentanil for intravenous (IV) PCA in a child scheduled for suprasellar arachnoid cystectomy with Axenfeld-Rieger syndrome who needed good postoperative analgesia because of accompanying serious problems.

Topics: Abnormalities, Multiple; Analgesia, Patient-Controlled; Analgesics, Opioid; Arachnoid Cysts; Child; Eye Diseases; Genes, Dominant; Heart Diseases; Humans; Infusions, Intravenous; Male; Monitoring, Intraoperative; Pain Measurement; Pain, Postoperative; Piperidines; Remifentanil; Syndrome

Topics: Abnormalities, Multiple; Adjuvants, Anesthesia; Agenesis of Corpus Callosum; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Anticonvulsants; Child; Eye Diseases, Hereditary; Female; Glycopyrrolate; Humans; Intellectual Disability; Laryngoscopy; Midazolam; Nitrous Oxide; Oral Surgical Procedures; Piperidines; Remifentanil; Spasm; Syndrome

A 58-year-old man presented with a history of disturbance in initiating gait. His history revealed meningoencephalitis five years prior to admission. Neurological examination included gait disturbance as difficulty in initiation and a hesitating speech with many freezing episodes and micrographia Magnetic resonance imaging (MRI) showed diffuse hyperintensity of frontal subcortical white matter on T2 weighted images. He was diagnosed with PA. L-Dopa up to the dosages of 1000 mg/ day and selegiline 10 mg/day were given. First brain SPECT using technetium-99m labeled D,L-hexamethylpropylene amine oxime (Tc-99m HMPAO) was performed when he was taking L-dopa and selegiline. In visual evaluation, hypoperfusion in bilateral frontoparietal cortex was seen (Fig. 2). Treatment with L-dopa and selegiline produced no benefit. Donepezil 10 mg/day was begun. This therapy regimen resulted in dramatic clinical improvement within several days that was confirmed by blinded raters who watched the patient's video recordings. During this response second brain perfusion SPECT study was repeated during donepezil therapy. Markedly increased perfusion in bilateral frontoparietal cortex was observed. This is the first case of PA to develop possibly after an episode of bacterial pneumococcal meningoencephalitis and who responded to donepezil as documented by changes in clinical findings and Tc-99m HMPAO brain SPECT studies.

Topics: Alexia, Pure; Brain; Cholinesterase Inhibitors; Dementia; Donepezil; Gait Disorders, Neurologic; Indans; Neurodegenerative Diseases; Piperidines; Radiopharmaceuticals; Recovery of Function; Syndrome; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Topics: Abnormalities, Multiple; Adjuvants, Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Atropine; Cleft Palate; Developmental Disabilities; Face; Female; Humans; Infant; Intellectual Disability; Intubation, Intratracheal; Methyl Ethers; Microcephaly; Midazolam; Muscle Hypotonia; Nitrous Oxide; Piperidines; Remifentanil; Sevoflurane; Syndrome

We describe the use of remifentanil in an infant with a partially repaired Shone's syndrome who required tendon lengthening because of congenital clubfoot. Remifentanil has unique properties, making it a potentially useful and predictable agent for infants with significant comorbidity.

Topics: Analgesics, Opioid; Anesthesia; Clubfoot; Heart Defects, Congenital; Humans; Infant; Male; Piperidines; Remifentanil; Syndrome

We studied the functional role of individual subtypes of muscarinic cholinoceptors in the pathogenesis of neuroleptic parkinsonism in rats. Blockade of M4 receptors prevented the development of extrapyramidal disorders, which was abolished by simultaneous blockade of M2 receptors. The data suggest that various subtypes of muscarinic receptors are involved in the regulation of dopamine concentration.

Topics: Animals; Catalepsy; Cyclopentanes; Diamines; Dopamine; Haloperidol; Male; Mandelic Acids; Muscarinic Antagonists; Piperidines; Receptor, Muscarinic M2; Syndrome; Trihexyphenidyl

We report two patients who developed Pisa syndrome after treatment with cholinesterase inhibitors--cognition-enhancing novel agents for patients with Alzheimer's disease. Cholinergic excess could be another factor in Pisa syndrome, especially in cholinergically-imbalanced Alzheimer's disease.

Topics: Aged; Alzheimer Disease; Carbamates; Cholinesterase Inhibitors; Donepezil; Dopamine Antagonists; Dystonia; Female; Humans; Indans; Memory Disorders; Middle Aged; Neuroprotective Agents; Nootropic Agents; Phenylcarbamates; Piperidines; Posture; Psychomotor Agitation; Risperidone; Rivastigmine; Syndrome

Topics: Aged; Diagnosis, Differential; Donepezil; Female; Hallucinations; Humans; Indans; Lewy Body Disease; Nootropic Agents; Piperidines; Syndrome; Vision Disorders

Parasympathetic hyperactivity is found in some infants presenting faint episodes and could be responsible of certain Sudden Infant Death Syndrome cases. Therefore it was interesting to look for a noninvasive biochemical indicator of parasympathetic activity. A parasympaticomimetic syndrome associated with muscarinic receptor stimulation, which has been followed during 48 h, was obtained in the awake rat by reserpine injection (6.25 mg/kg at T0 and T24h), and a model of prolonged parasympatholytic syndrome, by administration of diphemanil-methylsulfate (DPMS), a muscarinic receptor inhibitor, in drinking water (mean daily dosis: 150 mg/kg). Significant bradycardia and tachycardia were respectively observed. In the reserpine-treated rats we found significantly increased cyclic guanosylmonophosphate (cGMP) urinary excretion between T24h and T48h, when compared with vehicle-treated controls (+87% in one experiment, +135% in the other, when expressed in pmol/microg creatinine); norepinephrine urinary excretion between T24h and T48h was decreased (-44%); the increase in cGMP urinary excretion was not significantly modified by the NO-synthase inhibitor, L-nitroarginine-methyl-ester. In the DPMS-treated rats, we observed a significantly decreased cGMP (-20%) and increased norepinephrine urinary excretion (+61%). Thus cGMP excretion varied in opposite directions in the reserpine- and DPMS-treated rats. The link between these modifications in cGMP excretion and muscarinic receptor stimulation or blockade has still to be fully demonstrated. Urinary cGMP excretion could be tested as screening parameter in infants at risk of faint episodes associated with bradycardia.

Topics: Animals; Autonomic Nervous System Diseases; Cyclic GMP; Dose-Response Relationship, Drug; Heart Rate; Hemodynamics; Male; Muscarinic Agonists; Muscarinic Antagonists; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Norepinephrine; Parasympathetic Nervous System; Parasympatholytics; Piperidines; Rats; Rats, Sprague-Dawley; Reserpine; Syndrome

Despite progress, atherosclerotic vascular disease remains a major cause of morbidity and mortality. Intravenous therapy with platelet glycoprotein (GP) IIb/IIIa receptor antagonists improves outcome in patients with acute coronary syndromes (ACS). Whether potent long-term antiplatelet therapy with oral GP IIb/IIIa antagonists will further improve outcome at a dose that is tolerable in long-term treatment is unknown.. SYMPHONY (Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events post-acute cOroNary syndromes) was a randomized, double-blind, aspirin-controlled trial with 2 concentration regimens of sibrafiban, an oral peptidomimetic GP IIb/IIIa antagonist, for long-term treatment instead of aspirin in patients after an ACS. Patients were eligible for SYMPHONY if they presented within 7 days of an ACS (>/=20 minutes of ischemic symptoms), had been clinically stable for at least 12 hours, and met one of the following inclusion criteria: ST-segment depression or elevation of at least 0.5 mm or new left bundle branch block with the ACS or elevated creatinine kinase MB more than the upper limit of normal and >3% of total creatine kinase or, if creatine kinase MB was not measured, an elevated level of troponin T or I. Approximately 9000 patients post ACS were randomized 1:1:1 to treatment with either aspirin (80 mg every 12 hours) or high-dose or low-dose sibrafiban every 12 hours. Assignment of tablet strength (3, 4.5, or 6 mg) within the sibrafiban arms was based on body weight and renal function to achieve a target steady-state plasma concentration. The duration of study drug therapy was 90 days. Patients who had intracoronary stenting during the course of the study initially received a blinded stent medication assignment for 2 to 4 weeks based on their initial randomization as follows: aspirin/ticlopidine 250 mg twice daily, low-dose sibrafiban/ticlopidine placebo twice daily, and high-dose sibrafiban/ticlopidine placebo twice daily. After the second interim safety assessment by the Data and Safety Monitoring Board the stent regimen for the low-dose group was modified to include ticlopidine 250 mg twice daily.. The primary efficacy end point of SYMPHONY was the 90-day incidence of a composite of all-cause mortality, myocardial infarction or reinfarction, and severe recurrent ischemia. A clinical events classification committee was established to determine the end points of reinfarction and severe recurrent ischemia. The primary safety end points were the incidence of major bleeding or minor bleeding and the combined incidence of major and minor bleeding. Bleeding classification was done by computer algorithm. Tolerability was assessed by the rate of study drug discontinuation from bleeding.

Topics: Angina, Unstable; Aspirin; Clinical Trials, Phase III as Topic; Double-Blind Method; Humans; Myocardial Infarction; Oximes; Piperidines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prodrugs; Randomized Controlled Trials as Topic; Research Design; Syndrome; Treatment Outcome

Topics: Acute Disease; Antithrombins; Coronary Disease; Glycine; Heparin; Hirudin Therapy; Humans; Piperidines; Syndrome

Case of an infant with chronic cough is reported. The most frequent causes of chronic cough were ruled out. Twenty-four hour oesophageal pH-monitoring showed a close correlation between gastro-oesophageal reflux episodes and cough attacks. The patient was successfully treated with cisapride (0.3 mg/kg t.i.d.). These findings show that irritable oesophagus syndrome can cause chronic cough.

Topics: Chronic Disease; Cisapride; Cough; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Male; Piperidines; Sympathomimetics; Syndrome

During this investigation, which involved 58 Belgian White and Blue double-muscled calves affected by a naturally occurring Acute Respiratory Distress Syndrome, the clinical efficiency of a 5-HT2 receptor blockade with metrenperone (group A) was compared to the efficiency of a non-steroidal (flunixine meglumine--group B) and a steroidal (prednisolone sodium succinate--group C) antiinflammatory drug. Each animal of this trial was treated with ceftiofur sodium as antimicrobial agent. A clinical score and a breathing score were calculated at each step of the investigation period, i.e. before (T0) and 1 hour (T1), 12 hours (H), 24 H, 48H and 168 H (T3) after the first treatment, the interval 12H-48H being considered as period T2. Three clinical parameters were also taken into account separately: rectal and peripheral temperatures and heart rate. A significant improvement of the clinical score was registered at T2 in group A and at T3 in groups A and B, while this score did not significantly change in group C. In group A, the breathing score was significantly improved at T2 and T3, but not in groups B and C. Peripheral and rectal temperatures recorded at T1 were, in group A, significantly increased and decreased respectively, but not significantly changed in groups B and C. The proportions requiring change of treatment during the investigation period were significantly (P = 0.022) different in the three groups, being 5.6, 21.4 and 50.0% in groups A, B and C respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cattle; Cattle Diseases; Piperidines; Respiratory Insufficiency; Serotonin Antagonists; Syndrome

A 36-year-old woman with positional headache was found to have primary low cerebrospinal fluid (CSF) pressure syndrome and galactorrhea. The CSF pressure at lumbar puncture was not measurable. Magnetic resonance imaging demonstrated that the ventricle and cerebral sulcus were narrowed and the pituitary stalk was oppressed by the brain. Hyperresponsiveness of prolactin was noted after stimulation with thyrotropin-releasing hormone. These abnormalities disappeared with normalization of CSF pressure with the treatment. Galactorrhea was apparently due to oppression of the pituitary stalk by downward movement of the brain.

Topics: Adult; Cerebrospinal Fluid Pressure; Female; Galactorrhea; Headache; Humans; Hypothalamo-Hypophyseal System; Infusions, Intravenous; Magnetic Resonance Imaging; Piperidines; Posture; Syndrome

In vitro receptor-binding profiles and in vivo pharmacological studies have shown risperidone to be a potent mixed serotonin-S2 dopamine-D2-like receptor antagonist. While anti-D2 activity may relate to the antipsychotic potency of neuroleptic drugs, an antidepressive efficacy of substances with anti-S2 activity has been suggested. In an open pilot-study, ten patients with schizodepressive disorders or a DSM-III-R diagnosis of psychotic major depressive episodes were treated with risperidone (2-10 mg/d) for six weeks. Weekly psychopathological evaluation was performed, including BPRS, SANS, SAPS, VAS scales, and AIMS and UKU for the assessment of side-effects. Generally, the psychotic syndrome (BPRS, SANS and SAPS) decreased markedly in all patients; seven patients also showed a clinically significant improvement of depressive symptoms (BPRS). Except for two patients who needed biperiden because of extrapyramidal side-effects, the tolerance of risperidone was good. The antipsychotic and antidepressive properties of risperidone shown in our pilot study are promising enough to merit full double-blind controlled trials for further evaluation of its therapeutic value in this broad spectrum of psychiatric disorders.

Topics: Adult; Aged; Antipsychotic Agents; Depressive Disorder; Female; Humans; Isoxazoles; Male; Middle Aged; Piperidines; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Syndrome

After Roux-en-Y gastrojejunostomy patients frequently complain of upper abdominal pain, fullness, nausea, and vomiting. This Roux-en-Y syndrome is caused by slow gastric emptying, Roux-limb stasis, or both. Treatment of this syndrome is cumbersome. We evaluated the effect of cisapride on complaints and on transit through gastric remnant and Roux limb in 24 such patients. Thirteen of them had slow gastric emptying and 13 had stasis in the Roux limb (two patients had both). Symptoms and transit were evaluated before and after three weeks of treatment using a questionnaire and scintigraphy. Responding subjects continued therapy and were interviewed again after six months. Seven patients with slow gastric emptying and three patients with Roux-limb stasis had enduring symptomatic relief; all exhibited accelerated transit during therapy: mean half gastric emptying time in the seven patients with slow gastric emptying was 204 +/- 89 min before and 111 +/- 59 min during cisapride (P less than 0.05); mean percentage of radioactivity, emptied from the gastric remnant, which remained in the Roux limb at 60 min in the three patients with Roux limb stasis was 74 +/- 4% before and 25 +/- 10% during cisapride (P less than 0.05). In patients without symptomatic response, transit did not improve.. with cisapride long-lasting symptomatic relief and improved transit is achieved in about 40% of patients with the Roux-en-Y syndrome.

Topics: Adult; Aged; Anastomosis, Roux-en-Y; Cisapride; Female; Gastric Emptying; Humans; Jejunum; Male; Middle Aged; Piperidines; Postoperative Complications; Radionuclide Imaging; Serotonin Antagonists; Stomach; Syndrome

Topics: Acute Disease; Adult; Cisapride; Colonic Pseudo-Obstruction; Humans; Male; Piperidines; Serotonin Antagonists; Syndrome

1. The authors describe a case report of catatonia syndrome after administration of depot neuroleptics. 2. Differential diagnosis was made between neuroleptic malignant syndrome or catatonic syndrome complicated by infection. The signs and symptoms observed throughout the patient's course are detailed. 3. A critical review is made of bibliography on the topic, with emphasis on the lack of clear clinical description and poor conceptual definition.

Topics: Adult; Antipsychotic Agents; Biperiden; Catatonia; Delayed-Action Preparations; Diagnosis, Differential; Humans; Male; Neuroleptic Malignant Syndrome; Phenothiazines; Piperidines; Schizoid Personality Disorder; Syndrome; Thiazines

The mechanisms by which imipramine and dihydroergosine stimulate the 5-HT syndrome in rats and inhibit the head-twitch response in rats and mice were studied. Imipramine- and dihydroergosine-induced stimulation of the 5-HT syndrome was inhibited stereoselectively by propranolol, a high affinity ligand for 5-HT1 receptor sites, but not by ritanserin, a specific 5-HT2 receptor antagonist. (-)-Propranolol potentiated the inhibitory effect of imipramine, but not of dihydroergosine on the head-twitch response, while ritanserin was without effect. Neither imipramine nor dihydroergosine were able to stimulate the 5-HT syndrome in the animals pretreated with p-chlorophenylalanine. As expected, 8-OH-DPAT, a selective 5-HT1A receptor agonist, stimulated, and 5-HT1B agonists CGS 12066B and 1-(trifluoromethylphenyl)piperazine (TFMPP) failed to stimulate the 5-HT syndrome induced in rats by pargyline and 5-HTP administration. A higher dose of ritanserin inhibited the syndrome. While 8-OH-DPAT alone produced all behavioral components of the 5-HT syndrome, dihydroergosine or imipramine alone even at very high doses never produced tremor or a more intensive forepaw padding as seen when these drugs were given in combination with pargyline and 5-HTP. A single administration of (-)-propranolol also inhibited the head-twitch response. This effect lasted in mice longer than after ritanserin administration. In in vitro experiments dihydroergosine expressed approximately twenty-fold higher affinity for 3H-ketanserin binding sites than imipramine. The results suggest that imipramine and dihydroergosine possess two components--one stimulating the 5-HT syndrome in rats by a presynaptic, presumably 5-HT1A-mediated mechanism, and the other inhibiting 5-HT2 binding sites.

Topics: Animals; Brain; Ergotamines; Imipramine; Male; Mice; Mice, Inbred CBA; Motor Activity; Piperidines; Propranolol; Radioligand Assay; Rats; Rats, Inbred Strains; Ritanserin; Serotonin Antagonists; Syndrome

We report a case of vagal hypertonia syndrome in a newborn infant, developed after surgical repair of an aortic coarctation combined with banding of the pulmonary artery trunk. The parasympathetic activity had adverse repercussions on haemodynamics. The diagnosis was confirmed by prolonged asystole on the oculocardiac reflex and by concomitant arrhythmia and disorders of conduction demonstrated by Holter recordings. To our knowledge, no other case of vagal hypertonia associated with a congenital cardiopathy has yet been reported. Infants with this syndrome are at a high risk of sudden death. Treatment with vagolytic drugs is of questionable value, and prolonged supervision of the patient is mandatory.

Topics: Bradycardia; Cranial Nerve Diseases; Follow-Up Studies; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Parasympatholytics; Piperidines; Sudden Infant Death; Syndrome; Vagus Nerve

Both thresholds of nociceptive flexion reflex and pain sensation were studied in 6 normal subjects and in 6 patients with typical thalamic pain. In these patients, on the painful side, these thresholds were found increased (98 p. 100; 89 p. 100 respectively) compared to the normal side. Values obtained in this latter did not significantly differ from those observed in normal subjects. After 8 days of indalpine treatment, the nociceptive reflex threshold was furthered increased in the painful side while the pain threshold was not modified by this drug. In the normal side, changes observed after indalpine were similar to that obtained in normal subjects. All the indalpine-induced modifications were reversed by naloxone in both patients and normals. These results are discussed in the context of the possible mechanisms of thalamic hyperpathia.

Topics: Aged; Female; Humans; Male; Middle Aged; Naloxone; Pain; Pain Measurement; Piperidines; Reflex; Sensory Thresholds; Serotonin; Syndrome; Thalamic Diseases

The 5-hydroxytryptamine (5-HT) uptake inhibitor, paroxetine (11.6 mg/kg i.p.), given to rats pretreated with the monoamine oxidase inhibitor, phenelzine, 18 h (46.8 mg/kg i.p.) and 90 min (11.7 mg/kg i.p.) before, evoked a 5-HT-dependent syndrome which included wet-dog shakes (WDS). The frequency of WDS declined over the ensuing 3 h, at which time cortical 5-HT2 receptors showed a significant (30%) decrease in number. A second injection of paroxetine given at this time did not evoke a significant increase in the number of WDS, suggesting that spinal 5HT2 receptors might also have been down-regulated at the same time.

Topics: Animals; Cerebral Cortex; Ketanserin; Male; Myoclonus; Paroxetine; Phenelzine; Piperidines; Rats; Rats, Inbred Strains; Receptors, Serotonin; Serotonin; Syndrome; Time Factors; Tritium

The ergolene derivative MPME (PTR 17402; (5R,8R)-8-(4-p-methoxyphenyl)-1-piperazynylmethyl-6- methylergolene], a dopamine (DA) receptor agonist acting mainly at DA D-1 receptors linked to dotted types of forebrain DA nerve terminals, induces a characteristic behavioural syndrome consisting of increased locomotion, head-bobbing and sniffing activity without oral stereotypies or increased rearing. Haloperidol and cis-flupenthixol, nonselective DA receptor antagonists, but not selective D-2 receptor antagonists such as remoxipride and sulpiride, could significantly counteract the locomotion and head-bobbing behaviour induced by MPME. In contrast, the sniffing behaviour induced by MPME was only marginally affected by haloperidol and cis-flupenthixol pretreatment. These results suggest that activation of D-1 receptors in the forebrain mainly linked to the dotted types of DA nerve terminals in the striatum, and in the limbic forebrain, can result in behavioural effects which differ from those caused by stimulation of D-2 receptors located mainly within the diffuse types of DA nerve terminal systems.

Topics: Animals; Antipsychotic Agents; Apomorphine; Diencephalon; Ergolines; Humans; Male; Motor Activity; Nerve Endings; Piperidines; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D1; Stereotyped Behavior; Syndrome; Telencephalon

The efficacy of several drugs to elicit yawning and penile erections were determined in rats. The dopamine agonists, N-propylnorapomorphine, apomorphine, pergolide, (+/-)-3-PPP, TL-99 and N,N-dipropylamino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene (N,N-dipropyl A-5,6-DTN) all elicited yawning accompanied by an increase in spontaneous penile erections. The potencies of these drugs in causing yawning closely resemble published data concerning their actions in biochemical tests reputedly indicative of autoreceptor activity. In contrast, SK&F 38393, A-5,6-DTN and clonidine produced no yawning and few or no penile erections. Although physostigmine also caused yawning, the effect was not accompanied by penile erections. Studies with the optical isomers of 3-PPP showed that (+)-3-PPP was considerably more potent than (-)-3-PPP. Haloperidol antagonised dopamine agonist-induced yawning and penile erections. Apomorphine-induced yawning and penile erections were also antagonised by sulpiride and atropine but not by domperidone. The suitability of elicitation of the combined syndrome of yawning plus penile erections as useful behavioural model for dopamine autoreceptor agonists is discussed.

Topics: Animals; Apomorphine; Drug Interactions; Haloperidol; Inhalation; Isomerism; Male; Models, Psychological; Penis; Piperidines; Rats; Rats, Inbred Strains; Receptors, Dopamine; Respiration; Sexual Behavior, Animal; Syndrome

Topics: Adult; Aged; Biperiden; Delayed-Action Preparations; Drug Evaluation; Female; Humans; Male; Middle Aged; Parkinson Disease; Parkinson Disease, Secondary; Piperidines; Syndrome

Topics: 5-Hydroxytryptophan; Adult; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Myoclonus; Paroxetine; Piperidines; Serotonin; Serotonin Antagonists; Syndrome

Topics: Adolescent; Adult; Benzocycloheptenes; Drug Tolerance; Female; Humans; Male; Middle Aged; Migraine Disorders; Piperidines; Syndrome; Thiophenes

Topics: Delusions; Drug Combinations; Glycolates; Hallucinogens; Humans; Object Attachment; Piperidines; Pyrrolidines; Syndrome

Topics: Chronic Disease; Hallucinations; Humans; Mental Disorders; Piperidines; Psychopharmacology; Syndrome

Topics: Chlorpromazine; Humans; Parkinson Disease; Parkinsonian Disorders; Piperidines; Reserpine; Syndrome

Topics: Anti-Allergic Agents; Autonomic Agents; Biphenyl Compounds; Histamine H1 Antagonists; Humans; Phenothiazines; Piperidines; Psychotic Disorders; Syndrome

Topics: Humans; Piperidines; Somatoform Disorders; Syndrome

Topics: Bridged-Ring Compounds; Hallucinations; Humans; Mental Disorders; Piperidines; Psychotic Disorders; Syndrome; Urea

Topics: Hallucinations; Humans; Piperidines; Syndrome