PubMed Health⌕ Search

Biomedical subjects

J J Sramek

Publications and source records attributed to J J Sramek.

At least 19 recordsLinked to original sources
PubMed1992

Detection of benzodiazepines in human hair by radioimmunoassay.

OBJECTIVE: In this preliminary investigation, we sought to determine whether a standard benzodiazepine radioimmunoassay (RIA) could detect three benzodiazepines in human hair. DESIGN: Hair samples of 20-50 strands (minimum 10 mg) were cut from eight patients receiving diazepam, two patients receiving alprazolam, three patients receiving lorazepam, and two negative controls. Samples were treated with ethanol and phosphate buffer washes at 37 degrees C to remove external contamination. The protein hair matrix was destroyed using proprietary procedures, then analyzed with Abuscreen RIA designed to detect various benzodiazepines and their metabolites, using oxazepam as a reference standard. SETTING: Patients were hospitalized in a locked psychiatric facility. PATIENTS: Twelve patients with chronic psychiatric conditions who had received therapeutic dosages of benzodiazepines for 1-11 months were included in the sample. One outpatient who reported heavy prior diazepam use was also included. MAIN OUTCOME MEASURE: Detection of benzodiazepines was well above a 1.5 ng/10 mg cutoff level with the Abuscreen assay. RESULTS: Diazepam was readily detected, but alprazolam and lorazepam were not detected. CONCLUSIONS: There is no test that can currently determine duration and extent of prior benzodiazepine use. Hair analysis for diazepam offers a potential, new clinical and research tool for characterizing prior level and extent of usage.

Adult↗
PubMed1992

Implications of the study population in the early evaluation of anticholinesterase inhibitors for Alzheimer's disease.

OBJECTIVE: Velnacrine testing for tolerance and safety in both normal elderly subjects and patients with Alzheimer's disease (AD) is reviewed to illustrate the importance of Phase I trials in the target group as more predictive of safety and tolerance for subsequent multicenter trials than those conducted in healthy elderly subjects. DESIGN: Both a single-dose and a randomized, double-blind, placebo-controlled, ascending, multiple-dose study were performed with healthy, elderly men. In the multiple-dose study, the subjects were randomized to four groups of 14, with 10 subjects receiving velnacrine and 4 receiving placebo. The doses were velnacrine 25 (group 1), 50 (group 2), and 100 mg (group 3), respectively, administered twice daily; group 4 received 100 mg three times daily for 28 days. Blood and urine were collected serially for the pharmacokinetic assessment. With AD patients, 24 subjects were randomly assigned to receive either placebo or velnacrine for 10 days in a double-blind, sequential escalation study in a hospital setting. There were three groups of 8 subjects. Six patients in each group received velnacrine and 2 placebo. The three groups received respective dosages of 450, 300, and 225 mg/d three times daily. Adverse events were closely monitored and recorded. PATIENTS/PARTICIPANTS: The multiple-dose test in healthy elderly men included 56 men, aged 60-74 years. Rigorous screening for any potential complications that could affect absorption, distribution, metabolism, or excretion preceded patient entry in the AD patient study. Patients with a history of major psychiatric, neurologic, and cardiovascular disorders were excluded. The patients ranged in age from 56 to 89 years, and were equally distributed between gender. INTERVENTION: Velnacrine was administered in various doses. MAIN OUTCOME MEASURES: We emphasize the extreme adverse effects encountered in the AD patient group compared with the healthy group. Plasma concentrations of velnacrine over time in both groups are given, as well as the drug's half-life and excretion rates. RESULTS: The tolerable dosage predicted by studies performed in healthy elderly subjects was 300 mg/d. This dosage was not tolerable among the AD patients. A dosage as high as 450 mg/d resulted in a tonic seizure in one patient. The predicted dosage of 300 mg/d produced an adverse effect profile in AD patients that included dizziness, nausea and/or vomiting, headaches, and severe diarrhea. AD patients tolerated a dosage of 225 mg/d. CONCLUSIONS: A velnacrine dosage of 300 mg/d that was tolerated in healthy elderly subjects was not tolerated by AD patients.

Aged↗
PubMed1992

Pharmacokinetics and dose proportionality of D2-agonist MK-458 (HPMC) in parkinsonism.

To investigate the pharmacokinetic profile, bioavailability, and dose proportionality of the D2-agonist MK-458 (hydroxypropylmethylcellulose tablet, a sustained release formulation), a 4-period crossover study was conducted in 10 patients with mild to moderate Parkinson's disease (mean age = 63 y; 1 woman, 9 men). Following a titration phase to induce tolerance, each patient was given single oral doses of 6, 12 and 18 mg and a single intravenous 40 micrograms dose (5 micrograms/h over 8h). The maximum concentrations of MK-458 observed in plasma after oral administration were 139, 240 and 344 ng/L for the 6, 12 and 18 mg doses, respectively, and occurred after 8.0, 9.0 and 5.5 h, respectively. Mean areas under the plasma concentration-time curves were 1728, 2849 and 5484 ng/L.h, respectively. The mean plasma half-life was 3.8 h and mean plasma clearance was 3390 ml/min (203.4 L/h). The bioavailability (approximately 5%) was very similar for the 3 tablet formulations tested. The disposition of MK-458 was independent of the dose over the range of doses studied.

Administration, Oral↗
PubMed1991

Idioventricular rhythm: hypervagotonia associated with placebo.

We report a case of hypervagotonia manifested by idioventricular rhythm in a healthy, athletic man who participated in a Phase I study of an investigational calcium-channel blocker. Upon breaking the study's double-blind study code, it was discovered that the subject had received placebo. We discuss this unusual finding and the implications of including athletic subjects in safety/tolerance studies.

Accelerated Idioventricular Rhythm↗
PubMed1991

Adjunctive clonazepam in the treatment of chronic schizophrenia.

Clonazepam was added to the neuroleptic regimen of 3 treatment-resistant schizophrenic patients with schizoaffective features. Manic symptoms improved but returned following discontinuation of clonazepam. The drug appears to benefit positive psychotic symptoms but worsens negative symptoms.

Adult↗
PubMed1990

Patterns of neuroleptic usage in continuously hospitalized chronic schizophrenic patients: evidence for development of drug tolerance.

A retrospective review of neuroleptic dosages over a five-year period in 19 chronic schizophrenic patients revealed that the majority (85 percent) had either consistent yearly increases or decreases in dosage, although clinical status remained unchanged. The authors present differences in adverse effects between the two groups and discuss the implications of their findings for the concepts of neuroleptic drug tolerance and supersensitivity psychosis.

Adult↗
PubMed1988

High potency neuroleptics and violence in schizophrenics.

In a controlled study, inpatient violence was measured during placebo, high-potency (haloperidol) and low-potency (chlorpromazine or clozapine) neuroleptics. Some patients had a marked increase in violent behavior with the moderately high-dose haloperidol, but not with low-potency neuroleptics. The authors discuss reasons for the increased violence with haloperidol, including akathisia and drug-induced behavioral toxicity.

Adult↗
PubMed1988

Pharmacy-based screening program for tardive dyskinesia.

An ongoing screening program using pharmacists to detect tardive dyskinesia (TD) was developed, and a pharmacy-based prevalence survey of TD in chronic hospitalized psychiatric patients was undertaken to determine the extent of abnormal involuntary movements. The results show that older patients and women in particular are at higher risk for developing abnormal movements. Higher doses of neuroleptics were used in non-TD patients, indicating a possible masking effect caused by these drugs. By using a standardized rating method such as the Abnormal Involuntary Movement Scale, pharmacists can and should be utilized in the surveillance of TD.

Adolescent↗
PubMed1988

Neuroleptic plasma concentrations and clinical response: in search of a therapeutic window.

There is much interest in finding a therapeutic window for commonly used neuroleptics so that dosage can be individualized and side effects minimized. The authors review specific requirements of good study design and survey the literature that has investigated the relationship between therapeutic response and plasma concentrations of neuroleptics. The evidence from a number of fixed-dose haloperidol studies suggests, but does not yet prove, the existence of a therapeutic window for this compound.

Antipsychotic Agents↗
PubMed1987

Efficacy of adjunctive carbamazepine in the treatment of chronic schizophrenia.

Six treatment-resistant schizophrenic patients were given a ten-week single-blind trial of carbamazepine. Treatment resistance was determined on the basis of documented failure to respond to treatment with at least three neuroleptic drugs from two different chemical classes. The adjunctive use of carbamazepine resulted in a significant improvement of the negative symptoms of schizophrenia. These symptoms are often poorly responsive to conventional antipsychotic drugs. Therefore, controlled studies should be performed to further assess the possible efficacy of carbamazepine in schizophrenia.

Adult↗
PubMed1986

Neuroleptic dosage for Asians: a failure to replicate.

Retrospective chart review of 30 Asian patients and 30 matched Caucasian patients failed to replicate a previous report's finding that Asian patients require lower doses of neuroleptic medications than do Caucasian patients.

Adult↗
PubMed1986

An update on tardive dyskinesia.

The authors review recent research on definition, diagnosis, neuropathophysiology, treatment, management, and factors that increase risk of tardive dyskinesia, a severe and often unremitting movement disorder associated with neuroleptic treatment. Supersensitivity of dopamine receptors is believed to be the cause of tardive dyskinesia, and treatment strategies have consisted of pharmacologic blockade of dopamine receptors, depletion of dopamine, and restoration of the balance between the dopaminergic system and the neurotransmitter systems that regulate it. Several experimental neuroleptics that do not appear to cause tardive dyskinesia may be approved for use in the United States, but for now preventive measures, such as wise prescription and gradual tapering of neuroleptics, as well as careful monitoring for symptoms of tardive dyskinesia are the clinician's best defense.

Antipsychotic Agents↗
PubMed1986

Anticholinergic agents for prophylaxis of neuroleptic-induced dystonic reactions: a prospective study.

The development of acute dystonic reactions was monitored in 202 acute psychiatric patients during initial hospitalization and treatment with various neuroleptic drugs in a prospective study. Data were analyzed to determine the effect of anticholinergic prophylaxis, age, sex, and type and dosage of neuroleptic on the incidence of dystonic reactions. Nearly 90% of dystonic reactions occurred by the third day of treatment. The overall trend favored the prophylactic use of antiparkinsonian drugs with all neuroleptics, and the effect of this prophylaxis with haloperidol was statistically significant. Because anticholinergic prophylaxis was used more often when larger dosages of neuroleptics were prescribed, an added effect in the observed trend for fewer dystonic reactions is suggested.

Adolescent↗
PubMed1985

Hair analysis for detection of phencyclidine in newly admitted psychiatric patients.

The authors implemented a new procedure for analyzing phencyclidine (PCP) content in hair. They compare the results of analyses of hair with results of analyses of blood and urine in 47 patients newly hospitalized with acute psychiatric illness. Hair analysis identified 11 patients who had used PCP, and blood and urine analyses did not identify any among the sample population. In three patients, the results of hair analysis aided in establishing a diagnosis of PCP intoxication. The authors discuss interpretations of their findings and psychiatric applications of this new technique.

Adult↗