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Biomedical subjects

W H Wilson

Publications and source records attributed to W H Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Effects of marijuana on performance of a computerized cognitive-neuromotor test battery.

To evaluate the sensitivity of a computerized cognitive-neuromotor test battery in assessing the effects of marijuana (delta-9-tetrahydrocannabinol [THC]), we conducted a study of 10 healthy male volunteers who were experienced marijuana smokers. After extensive training on the performance tasks, each subject was tested on three separate days after smoking a cigarette containing either 1.75% THC, 3.55% THC, or placebo according to a randomized double-blind repeated measures design. Testing was carried out before smoking and 30, 90, and 150 minutes after smoking the cigarette. Of the five tasks employed, the digit-symbol substitution test with memory and the reaction time task were the measures most sensitive to effects of marijuana. We examined the usefulness of the coefficient of variation and effect size as indices of sensitivity to be used across different types of tasks.

Adult↗
PubMed1994

Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: a phase I/II trial of 96-hour infusion.

PURPOSE: A phase I study of paclitaxel infused over 96-hours was performed to determine toxicity, maximum-tolerated dose (MTD), and pharmacokinetics in patients with incurable lymphomas and solid tumors. A phase II study was performed at the MTD of paclitaxel in patients with doxorubicin/mitoxantrone-refractory metastatic breast cancer. PATIENTS AND METHODS: In the phase I study, paclitaxel dose levels ranged from 120 to 160 mg/m2, administered on a 21-day cycle. Patients with metastatic breast cancer who had either no response or a partial response (PR) to doxorubicin or mitoxantrone and had measurable disease were eligible for the phase I and II studies. Expression of the multidrug resistance (mdr-1) gene was determined in tumor biopsies by mRNA quantitative polymerase chain reaction. RESULTS: Twelve patients received a total of 73 cycles of paclitaxel on the phase I study. Dose-limiting mucositis and/or grade IV granulocytopenia was reached at 160 mg/m2, and 140 mg/m2 was selected as the phase II dose. Thirty-six consecutive patients with metastatic breast cancer were treated, of whom three were not assessable. The median age was 49 years, with disease in the liver and/or lung in 76%. Patients received a median of two prior regimens for metastatic disease, and 73% had no response to prior doxorubicin or mitoxantrone. Of 33 patients treated with paclitaxel, 16 patients (48%) achieved a PR and five (15%) achieved a minor response (MR). With a median potential follow-up duration of 60 weeks, the median progression-free and overall survival durations were 27 and 43 weeks, respectively. No correlation was found between extent of prior treatment or prior response to doxorubicin/mitoxantrone, and response to paclitaxel. Paclitaxel pharmacokinetics showed a correlation between both granulocyte and mucosal toxicity, and serum steady-state concentrations (Css) more than 0.07 mumol/L. Patients with liver metastases had significantly decreased paclitaxel clearance and higher paclitaxel Css. Levels of mdr-1 were uniformly low in all tumor biopsies studied. CONCLUSION: The recommended phase II dose of paclitaxel is 140 mg/m2 in patients without liver metastases and 105 mg/m2 in patients with liver metastases. Ninety-six-hour infusions of paclitaxel were effective and well tolerated in patients with doxorubicin/mitoxantrone-refractory breast cancer. Prolonged infusion schedules may be more effective than shorter schedules and deserve further study.

Adult↗
PubMed1994

Seizures associated with clozapine treatment in a state hospital.

BACKGROUND: The seizures associated with the atypical antipsychotic medication clozapine represent a serious side effect of treatment. In premarketing studies, seizures occurred at a crude rate of 3.5%. It is possible that the rate and character of seizures would vary in clinical settings because of differences in patient populations or differences in the manner in which treatment is administered. We studied the seizures that occurred during clozapine treatment in a state psychiatric hospital. METHOD: We reviewed the medical charts and pharmacy records of 100 sequential patients who were to start clozapine treatment. The review period covered 6 months pretreatment through 1 year of follow-up. RESULTS: The patients were 55 men and 45 women, aged 20 to 61 years. Ten (5 men, 5 women) had at least one seizure during clozapine treatment. Seizures occurred at all dose ranges (0-299 mg/day, N = 6; 300-599 mg/day, N = 2; 600-900 mg/day, N = 2). Of 12 patients with histories of previous seizures, 4 (33%) had a seizure while taking clozapine and anticonvulsants. Of 9 patients with histories of head trauma but no seizures, 1 (11%) had a seizure. Of 79 patients without seizure disorder or a history of head trauma, 5 (6.3%) had a seizure. Nine of the patients who had a seizure continued on clozapine treatment with temporary dose reduction and/or addition of an anticonvulsant, 2 having one additional seizure. CONCLUSION: Clozapine-associated seizures were more frequent in this group of state hospital patients than they were in premarketing studies. Clozapine-related seizures did not preclude successful treatment with clozapine.

Adult↗
PubMed1993

Depersonalization after marijuana smoking.

Depersonalization and other behavioral and physiological indices were monitored before and after the administration of high- and low-potency marijuana cigarettes and a placebo cigarette in 35 physically and mentally healthy normal volunteers. The cigarettes were administered under double-blind conditions during three visits to the laboratory separated by a minimum of 1 week. Marijuana smoking, but not placebo smoking, was associated with significant depersonalization that was maximal 30 min after smoking the high-potency cigarettes. Other behavioral changes induced by marijuana included disintegration of time sense, sensation of "high," increased state anxiety, tension, anger, and confusion. Respiration, pulse rate, and systolic blood pressure also increased after marijuana smoking. Multiple regression identified temporal disintegration as the most significant predictor of depersonalization.

Adult↗
PubMed1993

High-dose ifosfamide is associated with severe, reversible cardiac dysfunction.

OBJECTIVE: To determine the incidence and characterize the occurrence of cardiac toxicity with high-dose ifosfamide. DESIGN: Retrospective chart review. SETTING: Biomedical research referral center. PATIENTS: Fifty-two consecutive patients with advanced lymphoma or carcinoma enrolled in phase I trials of high-dose ifosfamide as part of combination chemotherapy with autologous bone marrow transplantation. INTERVENTIONS: Patients were given escalating doses (10 to 18 g/m2) of ifosfamide in combination with carboplatin and etoposide or with lomustine and vinblastine. MEASUREMENTS: The chart review focused on clinical, radiographic, or electrocardiographic evidence of cardiovascular dysfunction. Data from invasive hemodynamic monitoring, radionuclide cineangiography, and echocardiography were also reviewed. RESULTS: Nine of the patients treated with ifosfamide developed congestive heart failure (17%; 95% Cl, 8% to 30%). Eight of these patients, experiencing dyspnea, tachycardia, weight gain, and signs of pulmonary edema, required admission to an intensive care unit. Left ventricular contractility was found to be depressed when evaluated by radionuclide cineangiography, echocardiography, or both. Most patients responded to diuretic, vasodilator, and inotropic therapies. Two patients developed malignant ventricular arrhythmias. One patient died of intractable cardiogenic shock. Five patients died of multiorgan failure, despite showing improvement in left ventricular ejection fraction. Three patients survived and regained baseline left ventricular ejection fraction. CONCLUSIONS: High-dose ifosfamide is associated with severe but usually reversible myocardial depression and malignant arrhythmias.

Adolescent↗
PubMed1993

Addition of lithium to haloperidol in non-affective, antipsychotic non-responsive schizophrenia: a double blind, placebo controlled, parallel design clinical trial.

This double-blind placebo controlled, parallel design clinical trial compared the therapeutic effects of the addition of lithium or placebo to haloperidol in 21 seriously ill state hospital patients with DSM-III-R schizophrenia, who did not have concurrent affective disorders and who had not responded to previous trials of conventional antipsychotic medication. During a baseline period of 6 weeks, patients were switched to a stable dose of haloperidol (mean +/- SD dose = 13.6 +/- 8.1 mg/day). Patients were then randomized to receive either lithium or placebo in addition to haloperidol for 8 weeks (mean +/- SD lithium level = 0.98 +/- 0.13 mEq/l). Symptoms and side effects were assessed weekly. Improvement in symptoms correlated with the non-blind adjustment of antipsychotic dose, but not with lithium or placebo treatment. Side effects ratings did not differ between the two groups, but one patient developed a reversible delirium associated with combined lithium/haloperidol treatment. For these long-term, severely ill patients, combined treatment afforded no advantage over treatment with haloperidol alone.

Adolescent↗
PubMed1993

Acute changes in cerebral blood flow after smoking marijuana.

In experienced marijuana smokers, marijuana smoking was accompanied by a significant bilateral increase in cerebral blood flow (CBF) especially in the frontal regions and cerebral blood velocity. The post-marijuana CBF increase could not be explained on the basis on changes in general circulation or respiration. Similarly, the CBF increase was unrelated to plasma levels of tetrahydrocannabinol and extracranial circulation. Behavioral changes showed significant correlations with CBF. CBF and brain function are closely coupled and therefore it seemed highly likely that CBF changes after marijuana were closely related to its effect on mood and behavior.

Adult↗
PubMed1993

Isolation and Molecular Characterization of Five Marine Cyanophages Propagated on Synechococcus sp. Strain WH7803.

Five marine cyanophages propagated on Synechococcus sp. strain WH7803 were isolated from three different oceanographic provinces during the months of August and September 1992: coastal water from the Sargasso Sea, Bermuda; Woods Hole harbor, Woods Hole, Mass.; and coastal water from the English Channel, off Plymouth Sound, United Kingdom. The five cyanophage isolates were found to belong to two families, Myoviridae and Styloviridae, on the basis of their morphology observed in the transmission electron microscope. DNA purified from each of the cyanophage isolates was restricted with a selection of restriction endonucleases, and three distinguishably different patterns were observed. DNA isolated from Myoviridae isolates from Bermuda and the English Channel had highly related restriction patterns, as did DNA isolated from Styloviridae isolates from Bermuda and the English Channel. DNA isolated from the Myoviridae isolate from Woods Hole had a unique restriction pattern. The genome size for each of the Myoviridae isolates was ca. 80 to 85 kb, and it was ca. 90 to 100 kb for each of the Styloviridae isolates. Southern blotting analysis revealed that there was a limited degree of homology among all cyanophage DNAs probed, but clear differences were observed between cyanophage DNA from the Myoviridae and that from the Styloviridae isolates. Polypeptide analysis revealed a clear difference between Myoviridae and Styloviridae polypeptide profiles, although the major, presumably structural, protein in each case was ca. 53 to 54 kDa.

Journal Article↗
PubMed1993

Psychiatric disorders in adult children of alcoholics: data from the Epidemiologic Catchment Area project.

OBJECTIVE: The authors examined differences in the prevalence of psychiatric disorders in individuals who did or did not have alcoholic parents. METHOD: They used data from the National Institute of Mental Health Epidemiologic Catchment Area project, specifically from the Piedmont of North Carolina. Prevalence of psychiatric disorders was estimated in 408 ECA participants who reported problem drinking in their mother, their father, or both and in 1,477 age- and sex-matched subjects who did not report having alcoholic parents. RESULTS: The adult children of alcoholics showed significantly higher current (6-month) prevalence rates of simple phobia and agoraphobia and lifetime rates of dysthymia, generalized anxiety disorder, panic disorder, simple phobia, and agoraphobia. Adult children of alcoholics also had significantly more antisocial symptoms. Male children of alcoholics had higher rates of alcohol and drug abuse and reported more antisocial symptoms than did female children of alcoholics. Male children of alcoholics had a significantly higher rate of lifetime diagnoses of alcohol and drug abuse than men who were not children of alcoholics. More female children of alcoholics had generalized anxiety disorder than women who were not children of alcoholics. Both male and female children of alcoholics had significantly more antisocial symptoms than their matched comparison subjects. Sons of alcoholic fathers had a higher rate of substance abuse and more antisocial symptoms than did daughters of alcoholic fathers. Daughters of alcoholic fathers had a higher rate of generalized anxiety disorder. CONCLUSIONS: These data on adult children of alcoholics in a large community sample add to a literature based mainly on descriptive material or studies of smaller samples.

Agoraphobia↗
PubMed1993

EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma.

PURPOSE: Based on in vitro evidence that tumor cells are less resistant to prolonged exposure to low concentrations of the natural product class, compared with brief higher concentration exposure, we developed a chemotherapy regimen (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone [EPOCH]) in which the natural products are administered as a continuous infusion. PATIENTS AND METHODS: This is a phase II study of etoposide, vincristine, and doxorubicin, administered as a 96-hour continuous infusion, with intravenous (IV) bolus cyclophosphamide and oral prednisone (EPOCH) in 74 consecutive patients who relapsed from or failed to respond to most of the same drugs administered on a bolus schedule. Patients with aggressive lymphomas who achieved a good response after EPOCH were eligible to undergo bone marrow transplantation. RESULTS: Patients with intermediate- or high-grade lymphoma comprised 76% of this series and 77% had stage IV disease. Seventy-one percent had previously received all of the drugs contained in the EPOCH regimen and 92% had received at least four of the drugs. Seventy patients were assessable for response, of whom 19 (27%) achieved a complete remission (CR) and 42 (60%) a partial remission (PR). Among 21 patients who had no response to prior chemotherapy, 15 (71%) responded, but only one achieved a CR. Patients who relapsed from an initial CR had a 100% response rate, with 76% CRs. With a median potential follow-up duration of 19 months, there was a 28% probability of being event-free at 1 year. Toxicity was primarily hematologic with neutropenia during 51% of cycles, but only a 17% incidence of febrile neutropenia. Gastrointestinal, neurologic, and cardiac toxicity were minimal. CONCLUSION: EPOCH chemotherapy was well tolerated and highly effective in patients who were resistant to or relapsed from the same drugs administered on a bolus schedule, suggesting that continuous infusion of the natural drug component of this regimen is capable of partially reversing drug resistance and reducing toxicity. Dose-intensity (DI) was > or = that achieved in primary treatment regimens for aggressive lymphomas.

Adult↗
PubMed1993

Impact of clozapine on medication use in a state hospital.

Medical records of 90 consecutive patients who started clozapine were reviewed to see how this drug is being used with other psychotropic medications and to evaluate what impact it has had on the drug regimens of these patients. Data from up to 6 months before to 12 months after clozapine's initiation was included. The percent of patients receiving medications for antipsychotic side effects decreased from 86% 6 months prior to clozapine to 13% 12 months after. The use of benzodiazepines decreased from 43% to 23% during this time period as did lithium use from 57% to 17%. While 28% of the patients were receiving carbamazepine prior to starting clozapine, no patients remained on this drug concurrently with clozapine. The average number of psychiatric medications per patient decreased from 3.39 +/- 1.37 6 months prior to clozapine to 1.61 +/- .83 at month 12. Concern for drug interactions along with clozapine's reduced incidence of extrapyramidal side effects and increased efficacy contributed to the reduction in medication use observed.

Clozapine↗
PubMed1993

Treatment of social phobia with clonazepam and placebo.

Clonazepam and placebo were administered in a double-blind pilot study to 75 outpatients with social phobia. The mean maximum dose of clonazepam was 2.4 mg/day at endpoint (range, 0.5 to 3 mg). Treatment was continued for up to 10 weeks. The results of an intent-to-treat analysis indicated superior effects of clonazepam on most measures. Response rates for clonazepam and placebo were 78.3 and 20.0%. Drug effects were apparent on performance and generalized social anxiety, on fear and phobic avoidance, on interpersonal sensitivity, on fears of negative evaluation, and on disability measures. Significant differences were evident by week 1, 2, or 6, depending upon the rating scale used. Clonazepam was well tolerated in general, although unsteadiness and dizziness were more severe and persistent than was the case for placebo subjects.

Adult↗
PubMed1992

Mental neuropathy (numb chin syndrome). A harbinger of tumor progression or relapse.

The authors report four patients whose initial symptom of tumor recurrence or progression was unilateral numbness of the chin. Two patients had Hodgkin lymphoma, one had malignant melanoma, and one had prostate cancer. Physical examination was notable only for unilateral anesthesia of the chin and lower lip. Diagnostic evaluation, including computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain, plain radiographs of the mandible, and cerebrospinal fluid analysis for protein, glucose, and cytology were normal. Bone scans revealed osseous lesions in the axial skeleton of all patients, whereas only two patients had abnormal uptake in the mandible. The authors conclude that in the setting of a negative evaluation for central nervous system (CNS) or local mandibular disease, mental neuropathy is associated with recurrent or progressive skeletal disease. In addition, to document relapsed or progressive cancer, the skeletal system may have to be examined at sites distant from the mandible.

Adult↗
PubMed1992

Changes in middle cerebral artery velocity after marijuana.

Velocity of blood flow in the middle cerebral artery was measured with transcranial Doppler flowmeter before, during, and 1 hr after smoking a marijuana cigarette and a placebo cigarette during two separate visits to the laboratory. Ten healthy, right-handed male volunteers with a history of marijuana smoking took part in the study. The participants were drug-free for a minimum of 3 mo before the project. During the experiment, blood pressure, pulse rate, and end tidal levels of carbon dioxide were continually monitored. Marijuana smoking was associated with a significant increase in middle cerebral artery velocity. Although marijuana smoking was associated with increased pulse rate, the changes in blood velocity and pulse rate followed different time courses. Marijuana smoking was not associated with significant changes in blood pressure or end tidal carbon dioxide.

Adult↗