Biomedical subjects

C Clyde

Publications and source records attributed to C Clyde.

10 recordsLinked to original sources

PubMed1999

Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group.

BACKGROUND: We report the findings from the first large, double-blind, placebo-controlled study conducted to evaluate the efficacy and safety of risperidone in the treatment of psychotic and behavioral symptoms in institutionalized elderly patients with dementia. METHOD: 625 patients (67.8% women; mean age = 82.7 years) with DSM-IV diagnoses of Alzheimer's disease (73%), vascular dementia (15%), or mixed dementia (12%) and significant psychotic and behavioral symptoms were included. Each patient was randomly assigned to receive placebo or 0.5 mg/day, 1 mg/day, or 2 mg/day of risperidone for 12 weeks. The primary outcome measure was the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD). RESULTS: The study was completed by 70% of the patients. Baseline Functional Assessment Staging scores were 6 or 7 in more than 95% of the patients, indicating severe dementia. At endpoint, significantly greater reductions in BEHAVE-AD total scores and psychosis and aggressiveness subscale scores were seen in patients receiving 1 and 2 mg/day of risperidone than in placebo patients (p = .005 and p < .001, respectively). At week 12, 0.5 mg/day of risperidone was superior to placebo in reducing BEHAVE-AD aggression scores (p = .02). More adverse events were reported by patients receiving 2 mg/day of risperidone than 1 mg/day. The most common dose-related adverse events were extrapyramidal symptoms, somnolence, and mild peripheral edema. The frequency of extrapyramidal symptoms in patients receiving 1 mg/day of risperidone was not significantly greater than in placebo patients. CONCLUSION: Risperidone significantly improved symptoms of psychosis and aggressive behavior in patients with severe dementia. Results show that 1 mg/day of risperidone is an appropriate dose for most elderly patients with dementia.

Aged↗

PubMed1998

Cisapride 20 mg b.i.d. provides symptomatic relief of heartburn and related symptoms of chronic mild to moderate gastroesophageal reflux disease. CIS-USA-52 Investigator Group.

OBJECTIVE: We evaluated the efficacy and safety of a twice-daily dosage regimen of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal reflux disease (GERD) in patients with moderate intensity heartburn and no history of erosive esophagitis. METHODS: After a 2-wk, single-blind, placebo run-in period, 398 patients who continued to experience moderate intensity heartburn were randomized to either placebo (n = 196) or cisapride 20 mg (n = 202) twice daily for 4 wk. RESULTS: Compared with placebo, cisapride significantly reduced scores for daytime and nighttime heartburn (p < 0.001), total regurgitation (p < 0.001), eructation (p = 0.04), and early satiety (p = 0.04). Cisapride 20 mg b.i.d. was also superior to placebo in reducing total use of rescue antacid medication (p < 0.001); reducing, in concordance analyses, daytime and nighttime heartburn with antacid usage (p < 0.001); increasing the percentage of heartburn-free days and antacid-free nights (p < 0.5); and increasing the percentage of patients self-rated as having minimal or better symptomatic improvement (p = 0.01). Cisapride 20 mg b.i.d. was well tolerated. The most common adverse event in the cisapride group was diarrhea, reported by 10% of patients, compared with an incidence of 4% in the placebo group. CONCLUSION: Cisapride 20 mg b.i.d. was shown to be effective and safe for the short-term treatment of daytime and nighttime heartburn and for other symptoms associated with mild-moderate GERD.

Adolescent↗

PubMed1997

Ritanserin in the treatment of cocaine dependence.

Sixty-five cocaine-dependent subjects were enrolled into a 10-week randomized, double-blind study to determine the safety and efficacy of the serotonin-2 receptor antagonist, ritanserin (10 mg/day), in reducing cocaine consumption and craving. All subjects also participated in a structured intensive outpatient psychosocial program. Seventy-three percent of the participants completed the treatment program and follow-up. Subjects experienced a significant reduction in craving: 66.4% and 32.5% for the placebo and ritanserin groups, respectively. These reductions in craving were not paralleled by substantial decreases in cocaine use. Self-reported cocaine use was less frequent in the placebo group; paradoxically, blood levels of its metabolite, benzoylecgonine, were also higher although insignificantly so. Generally, ritanserin was well tolerated but significantly prolonged the QTc interval on the electrocardiogram. This outpatient program is effective at maintaining cocaine-dependent individuals in treatment and reducing craving. Ritanserin (10 mg/day) is not an efficacious adjunct to psychosocial treatment for cocaine dependence.

Adult↗

PubMed1997

A clinical evaluation of risperidone in the treatment of schizophrenia: a 10-week, open-label, multicenter trial. ARCS Study Group. Assessment of Risperdal in a Clinical Setting.

The efficacy and safety of risperidone have previously been demonstrated in controlled clinical trials in hospitalized chronic schizophrenia patients who met strict research criteria. The present study was designed to evaluate the efficacy and safety of risperidone in a heterogeneous patient population. Patients were enrolled in the study if they had a diagnosis of schizophrenia (DSM-III-R) with or without acute exacerbation. Of the 945 patients from 158 psychiatric centers who entered this phase IV study, 558 completed the 10-week trial. During week 1, the dose of risperidone was titrated to 6 mg/day, maintained there for 1 week, and then adjusted over a 4-week period as clinically necessary; the dose was then fixed for the final 4-week period. The mean dose of risperidone at endpoint was 5.9 mg/day. Patients were evaluated at baseline and at weeks 2, 6, and 10, using Clinical Global Impression scale, Psychotic Symptoms Assessment scale, and Global Assessment of Functioning scale. Significant improvement in mean scores was found on each of these measures at endpoint. Comparable results were obtained at week 10 in treatment-resistant and non-treatment-resistant patients. Risperidone was generally well tolerated and the severity of extrapyramidal symptoms was significantly reduced at endpoint.

Adult↗

PubMed1996

Ritanserin in the treatment of alcohol dependence--a multi-center clinical trial. Ritanserin Study Group.

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT2 receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects' QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence.

Adult↗

PubMed1993

Accelerated hyperfractionated hepatic irradiation in the management of patients with liver metastases: results of the RTOG dose escalating protocol.

PURPOSE: This study was prepared to address two objectives: (a) to determine whether progressively higher total doses of hepatic irradiation can prolong survival in a selected population of patients with liver metastases; (b) to refine existing concepts of liver tolerance for fractionated external radiation employing a fraction size which might be appropriate in clinical protocols evaluating elective or adjuvant radiation of the liver. METHODS AND MATERIALS: One hundred seventy-three analyzable patients with computed tomography measurable liver metastases from primary cancers of the gastrointestinal tract were entered on a dose escalating protocol of twice daily hepatic irradiation employing fractions of 1.5 Gy separated by 4 hr or longer. Sequential groups of patients received 27 Gy, 30 Gy, and 33 Gy to the entire liver and were monitored for acute and late toxicities, survival, and cause of death. Dose escalation was implemented following survival of 10 patients at each dose level for a period of 6 months or longer without clinical or biochemical evidence of radiation hepatitis. RESULTS: The use of progressively larger total doses of radiation did not prolong median survival or decrease the frequency with which liver metastases were the cause of death. None of 122 patients entered at the 27 Gy and 30 Gy dose levels revealed clinical or biochemical evidence of radiation induced liver injury. Five of 51 patients entered at the 33 Gy level revealed clinical or biochemical evidence of late liver injury with an actuarial risk of severe (Grade 3) radiation hepatitis of 10.0% (+/- 7.3% S.E.) at 6 months, resulting in closure of the study to patient entry. CONCLUSION: The study design could not credibly establish a safe dose for hepatic irradiation, however, it did succeed in determining that 33 Gy in fractions of 1.5 Gy is unsafe, carrying a substantial risk of delayed radiation injury. The absence of apparent late liver injury at the 27 Gy and 30 Gy dose levels suggests that a prior clinical trial of adjuvant hepatic irradiation in patients with resected colon cancer may have employed an insufficient radiation dose (21 Gy) to fully test the question.

Clinical Protocols↗

PubMed1993

Substantia nigra damage after fluorothyl-induced seizures in rats worsens after post-seizure recovery: no exacerbation with hyperglycaemia.

The substantia nigra pars reticularis (SNPR) of rats is highly susceptible to both seizure- and ischaemia-mediated damage. Hyperglycaemic exacerbation of brain damage similar to that observed after global brain ischaemia may also occur in rats with status epilepticus. We tested the hypotheses that hyperglycaemia exacerbates seizure-induced SNPR damage in rats and that SNPR lesions develop rapidly post-seizure. Halothane-anaesthetized, paralysed, and mechanically ventilated rats were prepared for haemodynamic and EEG monitoring. Halothane was discontinued, and mechanical ventilation on 30% oxygen/70% nitrous oxide was continued for 1 h. Three treatment groups (20 rats each) were studied: (1) control, lactated Ringer's solution; (2) equiosmolar control, 40% mannitol; and (3) hyperglycaemia, 50% dextrose. Infusions were started 5 min before seizures were induced with flurothyl 3% administered for either 45 (n = 10) or 75 (n = 10) min. Immediately after seizures, half of the animals underwent cerebral perfusion-fixation with formalin and half were allowed to recover for 2 h post-seizure and then perfused. Brain histology was assessed by light microscopy and scored 0-5 (0 = no damage) for the percentage of eosinophilic neurons and vacuolation in the SNPR. Glucose administration decreased the severity of SNPR damage in rats subjected to 75 min of seizures and 2 h recovery (pathology scores: control, eosinophilic neurons = 3.6, vacuolation = 4.0; hyperglycaemia, eosinophilic neurons = 3.0, vacuolation = 2.75; p < 0.05). SNPR damage was worse after 2 h of recovery (pathology scores: 0 h recovery, eosinophilic neurons = 0.9, vacuolation = 0.1; 2 h recovery, eosinophilic neurons = 3.9, vacuolation = 3.8; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗

PubMed1989

Expression of mammalian O6-alkylguanine-DNA alkyltransferase in a cell line sensitive to alkylating agents.

Chinese hamster ovary cells (CHO) were co-transfected with pSV2neo and sheared DNA from either a human cell line (HT29) expressing high levels of O6-alkylguanine-DNA alkyltransferase (AGT) or from a cell line (BE) deficient in this activity. Cells expressing the selectable marker were obtained by exposure to G418 and colonies resistant to alkylation damage isolated by growth in the presence of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). The number of colonies of cells expressing AGT activity arising after transfection with DNA from BE cells was similar to the number arising from cells exposed to HT29 DNA. Although the amount of AGT repair protein expressed in the transfectant colonies from this experiment was relatively low, these results indicate that repair of alkylation damage can be restored in AGT-deficient cells by transfection of human DNA from both repair-deficient and proficient cells. A separate transfection of CHOMG cells [a mutant of CHO cells resistant to the drug, methylglyoxal bis(guanylhydrazone) (MGBG)] with HT29 DNA and pSV2neo followed by selection of G418 and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) resulted in three colonies with high AGT levels. These transfectants had different growth rates and expressed levels of the AGT protein between 230 and 300 fmol/mg protein. The transfectants were as resistant to the cytotoxic effects of BCNU, Clomesone, methylnitrosourea (MNU) and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) as HT29 cells which were much more resistant than the parental CHOMG cells. Pretreatment of transfectant cells with 0.4 mM O6-methylguanine for 24 h reduced AGT activity to 14% basal levels, which upon removal of the base increased to approximately 74% basal level within 8 h. The sensitivity to the cytotoxic effects of both the chloroethylating and methylating agents was enhanced by treatment with O6-methylguanine. In the same manner, the number of BCNU-induced DNA interstrand cross-links increased in transfectant cells pretreated with O6-methylguanine. These results provide further evidence that the formation of methyl or chloroethyl adducts at the O6-position contribute significantly to cell lethality.

Alkylating Agents↗

PubMed1984

Defibrillators in general practice.

After a successful pilot scheme introduced in 1975, when six portable defibrillators were provided for health centres, an additional 50 defibrillators were provided in February 1982 for general practitioners to use. Between December 1975 and February 1984 defibrillation was attempted in 54 patients who collapsed with clinical cardiac arrest in the presence of general practitioners or less than five minutes before their arrival. A cardiac output was achieved in 32 patients, 28 survived to reach hospital via a mobile coronary care unit, and 22 were discharged alive. Of the 28 admitted to hospital, 24 were found to have myocardial infarction. If all general practitioners carried defibrillators they might make an important dent in the early mortality from myocardial infarction in addition to that achieved by a mobile coronary care unit.

Adult↗

PubMedDate not supplied

Pharmacokinetic profile of cisapride 20 mg after once- and twice-daily dosing.

Cisapride is a substituted piperidinyl benzamide. It is chemically related to metoclopramide but lacks the antidopaminergic properties of metoclopramide that affect the central nervous system and cause extrapyramidal side effects. Cisapride is indicated for the symptomatic treatment of patients with nocturnal heartburn due to gastroesophageal reflux disease. Based on extensive assessment of the drug's pharmacokinetic profile, the currently approved initial oral dosing regimen for cisapride is 10 mg QID. However, the pharmacokinetics of cisapride after oral administration of 20 mg BID have not been investigated. We present here findings from an open-label trial assessing the pharmacokinetics of cisapride 20-mg tablets after a single dose and at steady state (BID dosing). The results indicate that 20-mg BID and 10-mg QID regimens produce similar steady-state concentrations.

Adult↗