Biomedical subjects
I M James
Publications and source records attributed to I M James.
Muscle blood flow in diabetes mellitus. Evidence of abnormality after exercise.
OBJECTIVE: To determine whether muscle blood flow before and after exercise is abnormal in patients with diabetes mellitus. RESEARCH DESIGN AND METHODS: Muscle blood flow (MBF) was measured with the 133Xe clearance technique in 15 nondiabetic subjects, 10 patients with insulin-dependent diabetes mellitus (IDDM), and 11 patients with non-insulin-dependent diabetes (NIDDM) at rest and after exercise. None of the patients had neuropathy. RESULTS: The median resting MBF was similar in all three groups. The median postexercise MBF was significantly greater in nondiabetic subjects (40.1 ml.min-1.100 g-1 of tissue) than in patients with IDDM (25.7 ml.min-1.100 g-1 of tissue; P less than 0.01) or NIDDM (14 ml.min-1.100 g-1 of tissue; P less than 0.01). The difference between IDDM and NIDDM was not significant. CONCLUSIONS: Diabetic patients have abnormalities of MBF in response to exercise. This abnormality occurs in the absence of clinical diabetic neuropathy.
Blood pressure lowering and cerebral blood flow: a comparison of the effects of carvedilol and propranolol on the cerebral circulation in hypertensive patients.
The first part of this article concerns the general relation between blood pressure lowering and cerebral blood flow. Factors known to affect cerebral blood flow are reviewed, and recent advances in the field of innervation of cerebral blood vessels are outlined. Special emphasis is placed on the importance of the phenomenon of autoregulation and how this is disturbed in patients with hypertension. Not all antihypertensive drugs exert the same action on the cerebral circulation to produce the same blood pressure-lowering effect. In addition, the actions exerted by common antihypertensive drugs on the cerebral circulation are described. The second part of the article provides a comparison between the effect of carvedilol and that of propranolol on blood pressure reduction and cerebral blood flow. In a double-blind, crossover study involving 14 patients with mild-to-moderate hypertension, carvedilol was shown to have no effect on cerebral blood flow, whereas there was a slight tendency for lower flows to occur with the use of propranolol. Because of the small sample size, statistical significance was not reached. These results are consistent with other recently published findings.
The influence of hepatic cirrhosis on the pharmacokinetics of benazepril hydrochloride.
The influence of hepatic disease on the pharmacokinetics of the new ACE inhibitor, benazepril hydrochloride, was evaluated in 12 male patients suffering from liver cirrhosis. The patients received a single oral 20 mg dose. The plasma concentrations and urinary excretion of unchanged benazepril and its active metabolite benazeprilat were determined. Compared with a historical control group of healthy volunteers treated with the same benazepril. HC1 dose, the plasma concentrations of benazepril were doubled in the cirrhotic patients. However, the time to reach maximum concentration (0.5 h) was not affected. The plasma kinetics and the urinary excretion of the metabolite benazeprilat were not significantly altered: Area under the curve and maximum concentration as well as time to maximum concentration (1.5 h) were comparable with those in the healthy subjects. There was also no significant difference between the two populations for the total urinary excretion and the renal clearance of benazeprilat. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 94 per cent, respectively). In conclusion, the rate and the amount of bioactivation of the inactive prodrug benazepril to the active benazeprilat were virtually unaffected by hepatic cirrhosis. Thus, there seems to be no need for dosage adjustment of benazepril hydrochloride in patients suffering from cirrhosis of the liver.
Which antihypertensive?
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[Treatment of peritoneal carcinomatosis by intraperitoneal chemo-hyperthermia with mitomycin C. Initial experience].
Intra-peritoneal chemo-hyperthermia with mitomycin C was used to treat 9 patients with very advanced gastrointestinal cancers with peritoneal seedings. Resection of the primary tumor was possible in 3 cases. After temporary of closure of the abdominal wall, 90 to 120 minutes of intra-peritoneal chemo-hyperthermia was performed under general anaesthesia with 32 degrees C of systemic hypothermia, via 3 intra-peritoneal drains forming a closed circuit, using 10 mg/l of mitomycin C in 61 of peritoneal dialysate warmed at the inflow temperature of 46 to 49 degrees C. We observed no mortality or morbidity. There were only minor and temporary laboratory side effects and for 6 patients, no malignant cells could be found in the ascitic fluid after intra-peritoneal chemo-hyperthermia. In six patients, we conserved an improvement in the Karnofsky index 3 to 7 months after intra-peritoneal chemo-hyperthermia. These results show that intraperitoneal chemo-hyperthermia with mitomycin C is a safe and reliable treatment for peritoneal seedings in severely advanced gastrointestinal cancers and encourage us to proceed with this new therapeutic modality.
Pharmacologic effects of beta-blocking agents used in the management of glaucoma.
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Treatment of hypertension with captopril: preservation of regional blood flow and reduced platelet aggregation.
The BP of 12 patients with essential hypertension was controlled with captopril over a period of three months. Cerebral blood flow, muscle blood flow (anterior tibialis muscle), platelet aggregation and platelet thromboxane A2 release were measured during a baseline drug-free period, and measurements repeated during the treatment phase on achieving BP control, after one and three months. Cerebral blood flow rose during the early phase of treatment and then dropped to baseline levels during chronic therapy. Muscle blood flow, both at rest and following maximal exercise, was unaffected by captopril therapy. Platelet aggregation was diminished during therapy, and this finding was paralleled by a reduction in platelet thromboxane A2 generation. Control of hypertension with maintenance of regional blood flow and beneficial changes in platelet function during treatment with captopril may improve the overall risk profile of hypertensive patients. Inhibition of platelet aggregation and thromboxane A2 release may contribute to the antihypertensive action of captopril and the maintenance of regional blood flow.
Beta-blockers and acute situational stress.
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Prevalence of migraine in patients with diabetes.
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The clinical pharmacology of dihydroergotoxine mesylate (Hydergine).
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The effect of diflunisal administration on platelet aggregation and cerebral blood flow.
The effect of a high dose of diflunisal (750 mg twice daily) on platelet aggregation and cerebral blood flow was investigated in 8 healthy volunteers. Diflunisal inhibited platelet aggregation consistently; this effect on platelets was reversed within 24 hours after the last dose of diflunisal. There was, however, no correlation between the anti-aggregatory effect of diflunisal and its plasma concentration. Diflunisal did not alter cerebral blood flow.
Instability of cerebral blood-flow in insulin-dependent diabetics.
Cerebral blood-flow (CBF) was measured in 23 insulin-dependent diabetics before and 2--3 h after insulin/breakfast. In 10 of these patients CBF changed significantly during the day, with a significant fall in 9. In 3 patients who had the greatest falls in CBF there was a concomitant sensation of an impending faint. Thus CBF is unstable in insulin-dependent diabetics in contrast to control subjects in who there is little or no variation. Sudden falls in CBF in insulin-dependent diabetics may explain the symptoms of impending faint without hypoglycaemia; such falls would also be relevant to the pathogenesis of strokes in these patients.
Methods for assessment of the effect of drugs on cerebral blood flow in man.
The cerebral circulation is not an unimportant vascular bed but it is difficult one to investigate. Methodological difficulties are the main reasons for the paucity of clinical pharmacology studies to date. Of the methods currently available those of the McHenry (1964) and Wyper et al. (1976) appear to be the most useful to the clinical investigator. Increasing use of multiple detectors even with inhalation techniques may give evidence of regional drug effects upon the cerebral circulation. Improvements in methodology in the last few years, particularly the development of atraumatic methods are likely to act as an important spur to research in this field.
The effect of beta-adrenergic receptor blocking drugs on cerebral blood flow.
1 Cerebral blood flow (CBF) was measured by the 133xenon inhalation method in 33 newly-diagnosed hypertensive patients prior to commencing therapy. 2 Blood pressure was treated by using a varying sequence of four different drugs, namely labetalol, metoprolol, oxprenolol and sotalol, each of which is a beta-adrenergic receptor blocking agent, but with differing additional properties. 3 CBF measurements were repeated when blood pressure was controlled. No significant change in CBF was found with any of the four drugs, in contrast to the fall which has been reported when drugs of this type are administered acutely.
Comparative doses of four antihypertensive drugs.
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Comparison of effects on cerebral blood flow of rapid reduction in systemic arterial pressure by diazoxide and labetalol in hypertensive patients: preliminary findings.
1 Diazoxide 300 mg and labetalol 150 mg were each injected intravenously on separate occasions into five patients with essentail hypertension. The reduction in BP caused by labetalol was slightly greater than that produced by diazoxide. 2 In contrast the reduction in cerebral blood flow (CBF) by labetalol was not statistically significant, whereas diazoxide gave a greater and statistically significant reduction in CBF. 3 These observations suggest that labetalol may have an advantage over diazoxide for the rapid reduction in BP.
Abnormal cerebrovascular regulation in hypertensive patients.
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