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Biomedical subjects

J M Chubb

Publications and source records attributed to J M Chubb.

7 recordsLinked to original sources
PubMed1992

Human therapeutics based on triple helix technology.

The application of triple helix technology to rational drug discovery is rapidly leading to the development of a new class of drugs, initially applicable for the effective and specific treatment of viral infections and, eventually, perhaps, cancer and immunological disorders. Issues such as stability, delivery, specificity, in vitro efficacy and acute toxicity, and the cost of synthesis are already being addressed: preliminary studies are yielding promising results. Further chemical modification of the oligonucleotides will probably be necessary to enhance affinity and efficacy, and comprehensive studies on the pharmacokinetics, toxicity, mutagenicity and in vivo efficacy of these compounds are still required. These, as well as scale-up synthesis and pharmaceutical formulation issues, are the focus of the R&D programs of a number of pharmaceutical laboratories.

Base Sequence↗
PubMed1989

GR 38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis.

We evaluated, in a multi-center trial, the safety and efficacy of GR 38032F (GR-C507/75), a novel and selective serotonin antagonist, in preventing acute emesis in chemotherapy-naive patients receiving treatment with regimens containing high-dose cisplatin (greater than or equal to 100 mg/m2). Eighty-five patients were randomized to receive GR 38032F, 0.18 mg/kg, either every six or every eight hours for three doses, beginning 30 minutes before cisplatin. Patients were evaluated for emetic episodes (vomiting or retching) over a 24-hour period following cisplatin. All patients were evaluable for toxicity and 83 were evaluable for efficacy. The overall antiemetic response rate was 75% (55% complete response [CR], 20% major response). No difference in antiemetic control between the two administration schedules was noted. Patients with histories of heavy ethanol use had significantly better antiemetic control (74% CR) than modest or non-drinkers (33% CR). Toxicity of GR 38032F was modest and independent of administration schedule. The most common adverse events included mild hepatic transaminase elevations, self-limited diarrhea, dry mouth, headache, and mild sedation. Our data indicate that GR 38032F is a safe and effective agent in the control of acute cisplatin-induced nausea and vomiting. Additional trials exploring dosing, schedule, and comparison to standard antiemetic agents are indicated.

Acute Disease↗
PubMed1986

Effects of ethaverine hydrochloride on the walking tolerance of patients with intermittent claudication.

The effect of ethaverine hydrochloride on exercise tolerance of patients with intermittent claudication was evaluated in a double-blind, placebo-controlled study conducted at three sites. Forty-five patients with symptoms of occlusive arterial insufficiency of the lower extremities were randomly assigned to receive ethaverine 200 mg or placebo four times daily. The patients were evaluated biweekly for 12 weeks with treadmill claudication tests, patient and investigator assessments of symptom severity, and reports of adverse reactions. Doppler ankle/brachial pressure ratios were recorded for 26 patients. Walking tolerance improved for patients in both groups during the course of the study. Increases in distance-to-claudication were significantly greater for patients receiving ethaverine after 6, 8, 10, and 12 weeks of therapy. Ankle/brachial pressure index after exercise was unchanged in both groups. Incidence of adverse reactions was similar for the two groups. Although patients were generally unaware of any improvement in symptoms, the investigators judged significant relief of claudication among those receiving ethaverine compared to those receiving placebo. It was concluded that ethaverine safely increased distance-to-claudication in patients with intermittent claudication.

Ankle↗
PubMed1983

Ceftazidime, an open randomized comparison of 3 dosages for genitourinary infections.

Ceftazidime, a new beta-lactamase resistant aminothiazo-oyl cephalosporin with a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria, including Pseudomonas species, was evaluated clinically for efficacy and safety at 3 dosage levels in patients with acute genitourinary tract infection. Sixty patients with infections, including cystitis, pyelonephritis, epididymitis and prostatitis, were assigned randomly to 1 of the 3 dosage regimens: 250, 500 or 1,000 mg. administered intramuscularly every 12 hours. Patients were evaluated bacteriologically and clinically during the course of treatment and after treatment. All patients became asymptomatic and showed clinical improvement or cure within 48 to 72 hours regardless of dosage. Bacteriological success, namely eradication of the pathogen during therapy with no recurrence of superinfection during followup, was attained in 95 per cent of the patients with uncomplicated infections and in 61 per cent of those with complicated infections. Superinfections accounted for most of the noncures, particularly with the 250 mg. regimen. The difference in success rates between the 250 mg. dosage, and the 500 mg. and 1 gm. dosages in patients with complicated infections was statistically significant. Injections were well tolerated without significant side effects. No clinically important variations in laboratory tests were observed. The results indicate that ceftazidime is a useful third generation cephalosporin for complicated and uncomplicated genitourinary infections but it is recommended that the 250 mg. dosage not be used in patients with complicated infections.

Ceftazidime↗
PubMedDate not supplied

Relative bioavailability of a controlled-release albuterol formulation for twice-daily use.

A two-way-crossover bioavailability study was completed with 15 healthy male volunteers to evaluate the relative bioavailability of an orally administered controlled-release (CR) formulation of albuterol as compared to the immediate-release (IR) formulation of albuterol. The CR formulation of albuterol used in this study was based mechanistically on the elementary osmotic pump. Each subject received one 8 mg CR tablet every 12 h for 8 consecutive days and one 4 mg IR tablet every 6 h for 8 consecutive days, with 7 days separating each phase. During day 8 of dosing, hourly blood samples (0-12 h) were collected after the morning dose and three additional samples were obtained 16, 20 and 24 h following this dose. Plasma concentrations were measured using a gas chromatography-mass spectrometry procedure. No statistically significant differences were observed in mean steady-state values for Cmax, Cmin, AUC(0-12 h) and peak-to-trough fluctuations (PTF) in comparing the two dosage formulations. Mean steady state Tmax values were 2.6 and 6.0 h for the TR and CR formulations, respectively. It was concluded that twice daily administration of the controlled-release formulation of albuterol provides an alternative to four times daily administration of conventional (immediate-release) albuterol tablets.

Adult↗