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Biomedical subjects

M G Kirby

Publications and source records attributed to M G Kirby.

10 recordsLinked to original sources

Screening in general practice.

Screening for prostate cancer in a general practice setting seems to be technically feasible and generally acceptable. In our study, 14 cancers were diagnosed among the 568 men screened, giving an overall detection rate of 2%; five of these were either locally advanced or associated with metastatic disease. Although these results may reflect our somewhat conservative biopsy rate, there is a considerable false positive rate in the PSA range of 4-10 ng/ml, particularly among men with clinical evidence of benign prostatic hyperplasia. A large scale prospective controlled study will be necessary to establish the true benefit of screening.

Aged

Screening for carcinoma of the prostate: a GP based study.

OBJECTIVE: To examine the feasibility and acceptability of screening for cancer of the prostate by digital rectal examination (DRE), prostate specific antigen (PSA) determination and subsequent transrectal ultrasound (TRUS) in selected patients in a single general practice in Hertfordshire. SUBJECTS AND METHODS: A total of 568 of 856 men aged 55 to 70 accepted an invitation for a health check which included screening for prostate cancer. Of these, 80 individuals with either a raised PSA level or an abnormal DRE underwent TRUS. In 29 individuals biopsies were taken, 11 of which confirmed the presence of adenocarcinoma of the prostate giving an overall detected prevalence of 2%. Of the 11 tumours identified by screening, two were T1M0, four were T2M0, two were T3M0 and three were T3M1. RESULTS: To assess the acceptability of the screening exercise a postal questionnaire was sent to all 568 participants: 83% replied and 69% reported no concern. Of the 67 individuals who had undergone TRUS, 69% reported discomfort. A total of 448 (95%) of respondents declared that they would be prepared to undergo the screening exercise again. CONCLUSION: Screening for prostate cancer would seem to be technically feasible and generally acceptable. However, there is a considerable false positive rate in the PSA range 4 ng/ml to 10 ng/ml, particularly among men with clinical evidence of benign prostatic hyperplasia. To establish the true benefit of screening a large-scale prospective controlled study will be necessary.

Adenocarcinoma

Effect of altering small bowel transit time on sustained release theophylline absorption.

The relationship between variations in small bowel transit time (SBTT) and the absorption of theophylline from a sustained-release product was evaluated in a three-way, randomized, crossover study in 12 healthy male nonsmokers. Subjects received sustained-release theophylline (600 mg) with loperamide (8 mg every 6 hour x 8 doses). metoclopramide (15 mg every 6 hour x 8 doses) or placebo (every 6 hour x 8 doses). Theophylline solution (400 mg) was used as a reference standard. Serum samples were collected periodically for 72 hours for theophylline concentration determinations. SBTT was measured by the lactulose hydrogen breath test. Compared with placebo (98 +/- 53 min), SBTT was increased with loperamide (211 +/- 87 min; P less than 0.001) and decreased with metoclopramide (55 +/- 18 min; P less than 0.001). Loperamide decreased the rate, but not the extent of theophylline absorption from this product. This was evident from the reduced Cmax, the prolonged Tmax, and the decreased fraction of the dose absorbed at 24 hours, while the area under the curves remained the same. In contrast, metoclopramide had no effect either on rate or extent of absorption. The data suggest that the effect of loperamide on these absorption parameters was due to an increase in the dissolution time of this sustained-release product.

Adult

Effect of metoclopramide, bethanechol, and loperamide on gastric residence time, gastric emptying, and mouth-to-cecum transit time.

The effects of metoclopramide, bethanechol, and loperamide on the gastric residence time (GRT), gastric emptying (GE), and mouth-to-cecum transit time (MCTT) of a solution were investigated in three separate studies of five healthy male volunteers each. Metoclopramide in doses of 5, 10, and 15 mg prolonged GRT by 33, 88, and 162%, respectively, almost reaching statistical significance (p 0.058). A relationship was observed between GRT prolongation, and metoclopramide area under the plasma-time curve (p 0.01) and metoclopramide observed time to maximum concentration (p 0.01). Metoclopramide had an inconsistent effect on MCTT. Bethanechol 50 mg prolonged GRT by 64% (p 0.031) and had no effect on MCTT. Loperamide at doses of 2 and 8 mg prolonged GRT by 18 and 115% (p 0.043) and MCTT by 30 and 130% (p 0.0001), respectively. None of these motility-altering agents affected GE.

Adolescent

Effect of low-dose dopamine on the pharmacokinetics of tobramycin in dogs.

Low-dose dopamine or a placebo was given to six healthy mongrel dogs, each receiving tobramycin at 2.0 mg/kg on consecutive days in a randomized crossover fashion. Dopamine increased the total and renal clearances and elimination rate constant of tobramycin by 12.5, 20, and 25.9%, respectively, suggesting that low-dose dopamine increases the clearance of tobramycin in dogs primarily through renal mechanisms.

Animals

Pharmacology and therapeutic use of low-dose dopamine.

The renal pharmacologic effects of intravenous dopamine in doses of 0.5-3.0 micrograms/kg/min include increases in renal blood flow, glomerular filtration rate, solute excretion, and urine flow. Clinical studies revealed that low-dose dopamine can reverse oliguria, but these studies were poorly controlled, were confounded by the use of other diuretics, had small patient populations, and often did not evaluate mortality or long-term renal function. When used in low doses, side effects are rarely seen. Because of dopamine's effect on hepatic and renal function, changes in drug clearance may occur. Low-dose dopamine may be considered in the early course of oliguric patients; however, specific advantages over other diuretic therapy have not been established.

Anuria

A multicentre study of the safety and efficacy of amlodipine in mild to moderate hypertension.

An open, non-comparative study of 10 weeks' duration was conducted in general practice to assess the safety of amlodipine in patients with mild to moderate hypertension. Of the 5352 patients entering the study, 5135 received amlodipine; 4621 patients (90%) with a mean age of 58.2 years completed the study. Normalisation of blood pressure was achieved in over 80% of patients with a mean reduction of 21/15 mmHg. The mean final dose of amlodipine was 6.8 mg/day. Adverse experiences possibly related to amlodipine were reported by 19.3% of patients, and overall adverse events led to withdrawal in 6.7% of patients. The most common reported side-effect was oedema. The frequency of headache was almost identical in older and younger patients and oedema, flushing and dizziness were seen only slightly more often in elderly patients. Ninety per cent of patients were considered by their GP to have shown excellent or good toleration of therapy. Over 85% of patients elected to continue on amlodipine therapy after completion of the study.

Adolescent