Biomedical subjects
Publications and source records attributed to F M Hansen.
Hypercalcaemia is one of the extra-pulmonary symptoms of sarcoidosis. We describe a case of acute and chronic renal failure due to urolithiasis and nephrocalcinosis probably caused by sunlight-induced hypercalcaemia in a patient with undiagnosed sarcoidosis. Attention must be given to excessive sun exposure and vitamin D intake in patients with sarcoidosis.
In a prospective, randomized and placebo-controlled study we evaluated the influence of treatment with the calcium-channel blocker diltiazem on the course and results of cadaveric kidney transplantation in 39 graft recipients. The grafts were reperfused with Euro-Collins solution containing diltiazem 20 mg/l. All recipients except those in chronic treatment with a calcium-channel blocker received preoperatively a bolus of diltiazem or placebo 0.3 mg/kg and in all an infusion of diltiazem or placebo 3 mg/kg/24 h was started preoperatively. After that, diltiazem or placebo was given orally for 3 months. Donors were not treated. Immunosuppressive therapy consisted of prednisone, azathioprine and CsA. There were no significant differences between the groups concerning donor or recipient characteristics, HLA-mismatching, and ischaemic time. Thrombosis leading to graft loss occurred in 3 recipients (diltiazem:2, placebo:1) and one graft was lost due to septicaemia (diltiazem). For the remaining 35 grafts no beneficial effect of treatment with diltiazem was found for the rate of delayed graft function, the rate of rejections, time to first rejection, whole blood CsA concentration, or graft function. The CsA dose needed to reach target whole blood concentration was significantly less in the diltiazem group. In conclusion, our results do not indicate any beneficial effects of treatment with diltiazem in cadaveric kidney transplantation, except a reduction of costs because of a significant reduction of the CsA dosage.
This open uncontrolled trial was undertaken to evaluate the safety and the efficacy of a new angiotensin-converting enzyme inhibitor cilazapril in patients with both hypertension and renal impairment defined as endogenous creatinine clearance below 50 ml/minute. Twenty-five patients with a diastolic blood pressure from 95 to 115 mm Hg completed the trial. Blood pressure was measured pre-dose sitting and standing every week during placebo and every second week during active therapy, as well as two hours post-dose after placebo and at the end of active therapy. The dose of cilazapril was from 0.5 to 5.0 mg daily. After eight weeks of active therapy, a reduction in both pre-dose systolic and diastolic blood pressure was seen. No orthostatic effect on blood pressure was observed. The systolic blood pressure was better controlled as measured two hours post-dose compared with pre-dose, whereas no difference was found in diastolic blood pressure. No deterioration in kidney function occurred. Some cases of moderately increased serum-potassium were observed, especially in acidotic patients. No serious adverse reactions were observed.
A review is presented of antiglomerular basal membrane antibody-mediated glomerulonephritis (anti-GBM-Ab-nephritis) which constitutes 2-5% of all cases of acute glomerulonephritis. The disease frequently commences in the age group 20-30 years but may be encountered in all age groups, in women particularly at 60 years of age. The disease is due to autoantibodies (IgG) to the basal membranes in the glomeruli and alveoli. Deposition of IgG with C3 precipitates an inflammatory reaction which causes renal and possibly also pulmonary damage. It is possible to demonstrate anti-GMB-antibodies in the blood and, by means of immunofluorescence microscopy, these and C3 may be demonstrated in the basal membranes in the glomeruli and alveoli. The disease is still serious but introduction of immune-suppressive treatment and plasmapheresis has improved the prognosis considerably.
Insulin resistance was studied by comparing insulin response and insulin binding in four groups of rats. Glucose metabolism in isolated fat cells from male Wistar rats weighing 340 g was less responsive to a supramaximal dose of insulin than glucose metabolism in fat cells from rats weighing 200 g. Induction of streptozotocin-diabetes in rats weighing 200 g resulted in a marked decrease in the insulin responsiveness of fat cells. Ventromedial hypothalamic lesions of 340 g rats had the opposite effect and restored the insulin responsiveness of fat cells. The responsiveness in the four groups was correlated to the rate of glucose conversion to fatty acids in fat cells. The binding of 125I-insulin was the same in both 340 and 200 g rats. The ventromedial hypothalamic lesioned rats and the diabetic rats showed, in spite of their great difference in insulin responsiveness, the highest binding of 125I-insulin to fat cells. Insulin binding was not correlated to the plasma insulin level which however was reflected in the lipoprotein lipase activity in the adipose tissue. In conclusion, these results indicate that variations in insulin responsiveness in fat cells are due to alterations in cellular metabolism rather than in insulin binding.
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The metabolic consequences of ventromedial hypothalamic lesion were studied in a group of aged male rats which were obese and had decreased response to insulin. The effects of hyperphagia and ventromedial hypothalamic lesion per se were separated by comparing experimental animals fed isocalorically with controls and animals fed ad libitum. Ventromedial hypothalamic lesion as such led to increases in the glucose conversion to fatty acid and in lipoprotein lipase activity in adipose tissue. Protein catabolism as reflected by plasma urea levels, was enhanced. The lipoprotein lipase activity in heart tended to be lower after VMH lesion. These metabolic changes were amplified in the VMH lesioned rats fed ad libitum. The liver glycogen content was lowered by VMH lesion, but this effect was abolished by hyperphagia. In parallel experiments the influence of diet composition was studied by feeding similar groups with diet of high fat content. The glucose incorporation in fatty acids was in all groups markedly and similarly inhibited by the high fat diet. The increase in lipoprotein lipase activity in heart and adipose tissue of control rats with high fat intake could not be demonstrated in any of the groups with ventromedial hypothalamic lesion. The plasma urea level in the control group was not affected by the diet, but tended to increase in the ventromedial hypothalamic lesioned groups on high fat intake. These findings demonstrate that the well known metabolic effects of ventromedial hypothalamic lesions are also manifest in obese insulin resistant male rats. Furthermore, the responses to changes in diet composition are different from those of the control rats.
The significance of the hyperinsulinemia on the altered metabolism in ventromedial hypothalamus (VMH)-lesioned rats was tested. VMH lesions induced increases in fatty acid synthesis, lipoprotein lipase (LPL) activity, and plasma urea levels, and a decrease in plasma triglyceride concentrations. Similarly, in normal rats treated with pharmacological doses of insulin (14 U X rat-1 X day-1), fatty acid synthesis and LPL activity in fat tissue and the plasma urea were considerably elevated and plasma triglyceride was lowered compared with untreated controls. When endogenous insulin production was abolished by streptozotocin treatment, the four metabolic variables in the VMH-lesioned rats did not differ from those in diabetic controls. Substitution with 2 U of insulin X rat-1 X day-1, however, restored the differences in metabolism between VMH-lesioned diabetic and control diabetic rats. Substitution with 3 or 4 U insulin X rat-1 X day-1 showed the same differences. In VMH-lesioned rats the insulin level increased significantly from the 10th to the 70th day postoperatively; however, the rate of fatty acid synthesis, LPL activity, and plasma urea levels decreased, whereas plasma triglyceride concentrations increased. The results strongly suggest that the metabolic changes occurring after VMH lesions are only in part explained by the hyperinsulinemia associated with the VMH syndrome and indicate that other hormonal and/or nervous factors are involved.
The insulin-stimulated conversion of glucose to fatty acids (fatty acid synthesis) and the maximally norepinephrine-stimulated lipolysis were studied in isolated fat cells from normal male and female rats, ovariectomized rats and sexual hormone-treated normal and ovariectomized rats. The fatty acid synthesis and the lipolysis oscillated considerably more in fat cells from female rats than in fat cells from male rats. This was found to be due to the oestrous cycle, since the fatty acid synthesis was high in prooestrus and low in both oestrus and dioestrus, while the lipolysis was higher in oestrus and prooestrus than in dioestrus. Oestradiol treatment of both female and male rats and testosterone treatment of male rats for three days lowered the fatty acid synthesis and increased the lipolysis. The metabolic oscillation disappeared in ovariectomized rats, and the fat cells from these animals showed a metabolic pattern comparable with that found in prooestrus. Even when ovariectomized rats were treated with oestradiol or progesterone only three hours before the examination a significant lower fatty acid synthesis was found in oestradiol-treated animals compared with the progesterone-treated animals. Since these rats were fasted three hours before the experiments, the results were not due to differences in food intake. It is concluded that fat cell metabolism is influenced by sexual hormones. The results are compatible with the hypothesis that the variation in food intake due to sexual hormones is secondary to the metabolic changes.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.