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Biomedical subjects

J J Sramek

Publications and source records attributed to J J Sramek.

105 records · Page 6Linked to original sources
PubMed1983

Effect of lithium on leukocytes: a two-year follow-up.

Leukocytosis is a common finding in patients given lithium salts, but few studies have addressed the possibility of persistent leukocyte elevation during long-term lithium therapy. We followed leukocyte counts in 32 manic-depressive patients over a 1-year period and in 25 over a 2-year period of lithium therapy, after establishing prelithium leukocyte baselines. During the first few weeks, most patients showed significant increases, which persisted throughout the course of treatment. These findings indicate that lithium might play a role in the treatment of certain leukopenic conditions.

Adult↗
PubMed1982

Management of tardive dyskinesia: current update.

Tardive dyskinesia is now widely recognised as a neurological side effect produced in susceptible individuals by ingestion of neuroleptics. In general, the disorder tends to be late in onset, but has also been reported in a small number of individuals who have received neuroleptics for only brief periods. Much effort has been spent searching for predisposing factors, but the only consistent findings are that subjects are usually elderly (and elderly females in particular), in addition to having been exposed to neuroleptic agents. More recently, the increased finding of the presence of buccolingual facial movements in elderly populations never exposed to neuroleptics may bring out a re-evaluation of the role of these agents in the aetiology of tardive dyskinesia. Although much information on tardive dyskinesia has accrued in recent years, the precise definition, subtypes and pathophysiology remain unclear. With the development and availability of standardised rating scales, the clinical description of tardive dyskinesia has expanded from the initial buccolingual masticatory syndrome to include various abnormal movements of the fingers, arms, legs etc. Efforts have been made to distinguish withdrawal tardive dyskinesia from persistent tardive dyskinesia, but, irrespective of the classification, the disorder is in many instances reversible. However, it is impossible at present to predict the reversibility of each patient: therefore early detection of tardive dyskinesia remains an important clinical goal. Pharmacological treatments are based on the currently accepted hypothesis of dopamine receptor hypersensitivity. Selective dopamine blockers (D2) which suppress tardive dyskinesia without causing an increase in Parkinsonian symptoms are at various stages of development. Acetylcholine and gamma-aminobutyric acid (GABA) also appear to play a reciprocal role with dopamine as seen by moderate success using cholinergics and 'GABAergics'. However, there is no completely satisfactory treatment at present, indicating that prevention must be the primary aim. Above all, clinicians should carefully evaluate the indication for neuroleptic drugs, and avoid their use in conditions which may be treated with more benign drugs. A strategy for management of tardive dyskinesia is presented, and indications for withdrawing or continuing neuroleptics, the treatment of withdrawal dyskinesias and the role of experimental therapies are discussed.

Diagnosis, Differential↗
PubMed1982

'Loads' alert.

"Loads," a combination of glutethimide and codeine, are a relatively new form of drug abuse that is increasing in popularity in the Los Angeles area as a heroin-substitute. Preliminary findings based on interviews and treatment of a group of preferential Loads abusers seen over a one-year period suggest that this combination has a potential for serious intoxications and withdrawal complications. The common withdrawal symptoms include those produced by both a sedative-hypnotic and a major narcotic and necessitate a detoxification plan based on the pharmacologic rationale of the abused combination.

Adult↗
PubMed1981

"Loads".

Explore the source record for details and available documents.

Codeine↗
PubMed1981

Psychotic exacerbation with haloperidol.

A case illustrating the worsening of a patient's schizophrenic symptoms following haloperidol dosage increases in presented. This case is remarkable in that few cases of psychotic exacerbation with haloperidol dosage increases have been reported in the world literature. The possibility exists that, like certain tricyclic antidepressants, neuroleptic medication may possess a "therapeutic window,". The concept of a therapeutic window and its relationship to the phenomenon of psychotic exacerbation is reviewed. In evaluating this condition, the clinician should consider other causes of psychotic exacerbation, such as akathisia and anticholinergic psychosis.

Adolescent↗
PubMedDate not supplied

Pilot study of a CCKB antagonist in patients with panic disorder: preliminary findings.

L-365,260 is a CCKB antagonist which has been shown to completely prevent CCK-4-induced symptoms of panic attack in single-dose (50 mg) placebo-controlled studies in patients with panic disorder. The present report is data from one site (n = 38) in a multicenter study (n = 88) designed to assess the preliminary efficacy and safety of L-365,260 in patients meeting DSM-III-R criteria for panic disorder, with or without agoraphobia. In order to participate, male and female patients were between 18-55 years of age and in good physical health. Following a one-week single-blind placebo lead-in, patients were randomized to 30 mg four times daily of L-365,260 (n = 18; 7 M, 11 F) or placebo (n = 20; 9 M, 11 F) for six weeks. At end of study, none of the efficacy measures, including the frequency of panic attacks, the Physician's Global Improvement Scale, and the Hamilton Rating Scale for Anxiety, were significantly improved over baseline values. L-365,260 was well-tolerated; the most common drug-related adverse events were headache and lightheadedness. Further testing of L-365,260 at higher dosages, or testing of other CCKB antagonists, is required to rule out the usefulness of this novel treatment approach.

Adolescent↗
PubMedDate not supplied

Efficacy and safety of two dosing regimens of buspirone in the treatment of outpatients with persistent anxiety.

This randomized, double-masked, comparative study evaluated the efficacy and safety of buspirone 30 mg/d, administered twice a day (BID) or three times a day (TID), in patients with generalized anxiety disorder (GAD), commonly called persistent anxiety. Patients who participated had GAD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders. Third Edition, Revised, modified to include patients for whom the symptom duration was at least 4 weeks and scored > or = 18 on the Hamilton Rating Scale for Anxiety (HAM-A). After a 7-day placebo lead-in phase, patients who continued to qualify were randomized to receive buspirone, titrated from 15 mg/d (5 mg TID) to 30 mg/d, as either a BID or TID regimen, for 8 weeks. Of the 137 patients who began the study, 120 patients were included in the data evaluation. Both buspirone BID and TID treatment groups demonstrated significant reductions in mean HAM-A total scores and improvement on Clinical Global Impression measures, with no significant differences detected between the two treatment groups for either measure at any time point. The overall incidence of adverse events was similar for both treatment groups, except for a significantly greater incidence of amblyopia in patients receiving buspirone 15 mg BID. In summary, there was no appreciable difference in efficacy or safety between buspirone 15 mg BID or 10 mg TID in patients with persistent anxiety.

Adolescent↗
PubMedDate not supplied

RBC cholinesterase inhibition: a useful surrogate marker for cholinesterase inhibitor activity in Alzheimer disease therapy?

Red blood cell (RBC) acetylcholinesterase (AChE) inhibition has been used as a peripheral surrogate marker for the activity of centrally acting AChE inhibitors (AChEIs) in the treatment of Alzheimer disease. As a valid peripheral surrogate marker, RBC AChE inhibition should reflect the central pharmacodynamic activity of the compound and should demonstrate a relation with cognitive or global improvement in patients with Alzheimer disease. As a useful clinical tool, RBC AChE inhibition should also provide an advantage in dose optimization. However, the application of surrogate markers in research and clinical use is controversial (Prentice, 1989; Gotzsche, 1996; Colburn, 1997; De Gruttola et al., 1997). For instance, surrogate markers that have been identified or applied inappropriately can lead to erroneous conclusions, slowing the drug development process (Colburn, 1997). Also, the validation of surrogate markers for the pharmacodynamic activity of central nervous system drugs is not always possible because samples of brain tissue cannot be analyzed in humans. Finally, although validation of peripheral markers for central nervous system drugs has been approached via analysis of cerebrospinal fluid (Cutler et al., 1998a), few markers have been subjected to such rigorous evaluation in clinical studies. The extent to which measures of peripheral AChE inhibition accurately model central drug activity and therapeutic effectiveness of AChEIs, both as individual agents and as a drug class, is the focus of this review. AChEIs comprise a group of structurally diverse compounds with a wide range of relative specificities for the various molecular species of cholinesterase found in plasma, RBCs, and the brain. Studies of RBC AChE inhibition after administration of AChEIs in animals are of limited utility because of the differential sensitivity of AChEIs for human versus animal forms of AChE, the poor correlation between effective doses in animals and humans, and the lack of standardized measurements of effectiveness. Although clinical studies of donepezil, metrifonate, and eptastigmine have suggested the potential use of RBC AChE inhibition as a predictor of clinical response, the degree of inhibition yielding maximum cognitive improvements was highly variable from compound to compound (30-80%). Further, investigators did not prove a relation between central and peripheral pharmacodynamics or demonstrate an advantage over dose in the ability of RBC AChE inhibition to predict clinical response. A study of rivastigmine in patients with Alzheimer disease revealed that cerebrospinal fluid AChE inhibition correlated well with cognitive performance, whereas peripheral inhibition did not. Therefore, RBC cholinesterase inhibition is not a reliable surrogate marker for the activity of AChEIs as a class of drugs, and its usefulness as a dose optimization tool for individual agents has yet to be demonstrated clearly.

Acetylcholinesterase↗
PubMedDate not supplied

Alzheimer's patients should be included in phase I clinical trials to evaluate compounds for Alzheimer's disease.

Dosage and tolerance are critical issues in successful drug therapy for patients with Alzheimer's disease (AD). A clear distinction among patient populations and AD patient subpopulations is necessary to ensure a thorough assessment of new central nervous system-active compounds. Phase I inpatient trials, in which tolerance and safety are evaluated under double-blind conditions in the target population, provide valuable information for use in planning multicenter outpatient trials. In similar studies, even those involving the elderly, tolerance and safety outcomes in healthy volunteers are not always predictable. An early trial of the effects of velnacrine in healthy, elderly, male volunteers was followed by a trial in the target population. A group of volunteers, aged 60 to 74 years who did not have AD, received 300 mg of velnacrine each day. This dosage was well tolerated for 28 days. Diarrhea, generally of moderate severity, was the only reported adverse effect. No subjects were required to discontinue taking velnacrine. In contrast, a similar trial showed a dosage of 300 mg of velnacrine each day intolerable among patients with AD. Adverse reactions to dosages greater than 225 mg/day included dizziness, fainting, nausea and/or vomiting, headache, and severe diarrhea. A velnacrine dosage of 225 mg/day appeared to be safe and well tolerated in a small population of healthy patients with AD. Based on the inpatient experience with AD subjects, a maximum dose of 225 mg/day was adopted for outpatient studies. Although factors that may contribute to drug sensitivity in patients with AD vary beyond conclusive parameters, the observed sensitivity within the target AD group may indicate a safety/tolerance study as a worthwhile antecedent to multicenter efficacy trials.

Administration, Oral↗
PubMedDate not supplied

A new assessment tool for neuropsychopharmacologic research: the Computerized Neuropsychological Test Battery.

The Computerized Neuropsychological Test Battery (CNTB), a new assessment tool for neuropsychopharmacologic research, is based on a neuropsychological approach. While it is based on tests previously shown to be sensitive to subtle changes in neuropsychological functioning, it differs from currently available tools for measuring central nervous system effects of new compounds. It has sensitivity to a broader range of cognitive functioning and is more comprehensive than other measurements in its sampling of neuropsychological functions, providing wider application to diverse clinical populations. The CNTB is valid, reliable, and has two alternative forms. Use of the computer as an expert system maximizes standardization and ease of CNTB administration and data analysis. Using this assessment tool, three groups of subjects were compared: young and elderly neurologically normal subjects and elderly subjects with the dementia syndrome of Alzheimer's disease (AD). The AD subjects' summary score on the CNTB correlated significantly with the Blessed Information Memory Concentration Test score. The CNTB summary score was significantly higher in young subjects than in neurologically normal elderly subjects, demonstrating sensitivity to the effects of aging. The CNTB summary score also was significantly higher in neurologically normal elderly subjects than in elderly subjects with AD dementia.

Adult↗
PubMedDate not supplied

Evaluation of multiple doses of milacemide in the treatment of senile dementia of the Alzheimer's type.

A multicenter, double-blind, placebo-controlled, parallel group study was conducted to assess the safety and efficacy of three doses of milacemide in the treatment of patients with senile dementia of the Alzheimer type of mild to moderate severity. Patients were randomly assigned to receive one of three dosages of milacemide (400, 800, or 1200 mg/day) or placebo for 4 weeks followed by a single-blind 4-week placebo period. One hundred forty-eight men and women older than 50 years of age were enrolled, and 129 patients completed the study. The differences among treatment groups were not statistically different with respect to total scores on the Alzheimer's Disease Assessment Scale or any items and subscales that were examined, nor were significant differences on the Clinical Global Impression Scale found. Clinically significant increases in liver function tests, specifically aspartate aminotransferase and alanine aminotransferase (AST and ALT), were reported for five of the patients receiving milacemide, requiring their withdrawal from the study.

Acetamides↗
PubMedDate not supplied

Ethnicity and antidepressant response.

Modern psychopharmacology provides us with several effective antidepressants. We are increasingly recognizing the importance of interindividual differences in plasma concentration with these drugs. Such differences are caused by genetics, and the more extreme variations result from the population classified as slow hydroxylators. We now recognize that there are also substantial racial differences in the frequency distribution of slow metabolizers. The importance of studies in this area has been underscored by anecdotal reports as well as cross-cultural surveys of prescribing patterns which indicate that antidepressant dosage requirements may differ among racial groups. This review will focus on the relatively young field of cross-cultural psychopharmacology and the efforts being made to determine the importance of society, culture, environment, genetics, and biophysiology in the prescribing and metabolism of and response to antidepressant drugs.

Antidepressive Agents↗