Search

Provides updates related to medicine in Great Britain as of July 1976. Prosthesis for vascular access; Capability of lithium carbonate to produce antinuclear antibodies; Analysis of an ocular involvement in cytomegalovirus infection in a previously healthy adult.

In this study, human platelets were used as a cellular model for exploring cytosolic free Ca (Cai) regulation in non-insulin-dependent diabetes mellitus (NIDDM). Cai levels were monitored in resting and thrombin-stimulated platelets from obese females with NIDDM; obese, nondiabetic women, and nonobese, nondiabetic women. All subjects were black. Significant and marked elevation of basal Cai levels was observed in platelets from the diabetic subjects when no aspirin was used during platelet isolation. However, no significant differences were observed in Cai between aspirin-treated platelets from women with NIDDM and platelets from nondiabetic women. The rate of the Cai return to basal level after thrombin stimulation was significantly lower in platelets from the diabetic subjects, suggesting an abnormality in platelet Ca extrusion or sequestration in NIDDM. Platelet Cai levels positively correlated with low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL/HDL) and fasting blood glucose. These findings suggest abnormalities in platelet Cai homeostasis in NIDDM that are influenced by the serum lipid profile and perhaps glucose.

Objective: To study differences in cytosolic free calcium regulation between African Americans and Caucasians, using platelets as a model for studying cellular physiology., Design: Platelet calcium regulation in apparently healthy African American and Caucasian males was examined., Methods: Using fura-2, calcium influx and cytosolic calcium extrusion were monitored after treatment with thapsigargin, an inhibitor of the Ca-ATPase in the dense tubular membrane system., Results: Compared with Caucasians, platelets from African Americans demonstrated a higher calcium influx into the cytosol (from the external medium and dense tubular membrane system), as well as enhanced calcium extrusion from the cytosol., Conclusions: Such findings indicate that platelets from African Americans have increased intracellular calcium stores or increased cellular calcium turnover, or both. If these racial differences involve other cells, such as vascular smooth muscle cells, they could underlie the predisposition of African Americans to essential hypertension.

Previously, we demonstrated that removal of fetal bovine serum (FBS) from the medium of human skin fibroblasts resulted in an accelerated 86Rb+ washout, decreased cellular K+, and increased Na+ contents. In the present study we examined the mechanism underlying these changes. The efflux rate constant for 86Rb+, and the cellular contents of Na+ and K+ were measured. Verapamil (K1/2 = 15 microM) and chlorpromazine (K1/2 = 1 microM) reduced by approximately 70% the increased 86Rb+ washout evoked by FBS removal. The effect of the two drugs was additive at low, but not high, concentrations. Verapamil and chlorpromazine also attenuated the decrease in cellular K+ content and prevented the increase in cellular Na+ content associated with FBS depletion. Bumetanide (50 microM) was only partially effective in offsetting the enhanced 86Rb+ efflux and was completely without any effect on the cellular Na+ and K+ changes induced by FBS removal. In the presence of FBS, A-23187 produced a slight and transient increase of the 86Rb+ washout. The protein kinase C activator phorbol 12-myristate 13-acetate enhanced the 86Rb+ efflux in FBS-containing medium for a prolonged period but this increase was only a fraction of that caused by serum removal. Cellular Na+ and K+ contents were not changed by the phorbol ester. We conclude that FBS removal raises the cellular Na+ content, and enhances 86Rb+ efflux, through a calmodulin-dependent pathway activated by calcium influx.

Clinical decision-making conference will be a new quarterly feature. Suggestions or contributions should be addressed to the authors. The authors discuss a 67-year-old male with coronary heart disease and renal failure.

This paper is a brief commentary of the role of forced diuresis and hemodialysis in the treatment of acute poisoning. The importance of informed conservative management is stressed. Rationale and methods of forced diuresis and urinary alkalinization are presented. Dialysis is reserved for special situations where shortening the poison-patient contact time is indicated.

Actuarial statistics of 53 dialysis patients treated between 1965 and 1976 are reviewed. It is suggested that dialysis did not accelerate atherosclerosis over the observed time period. It appears as though a fundamental change in the dialysis population has occurred and there are too few long-term dialysis patients available to establish whether dialysis does accelerate atherosclerosis.

Five main aspects were addressed: 1)The demonstration that creatinine is an endogenous precursor of dimethylamine (DMA) in chronic renal failure. 2) The size of the body amine pool measured in transplant patients suggests sequestration in some intracellular compartment. This illustrates the possible error in directly relating serum concentrations to neurological toxicity. 3) Bacterial overgrowth and increased generation of duodenal DMA in the small intestine becomes apparent at a serum creatinine above 8 mg/dl. Two cases show that bacterial overgrowth preceded the increased duodenal DMA. 4)Clinical toxicity is demonstrated by i) correlation of abnormal neurobehavioral parameters with serum amine levels, and ii) by improvement with administration of nonabsorbable broad spectrum antibiotics. Results with adsorption agents are inconclusive. 5) Preliminary tests of behavior modification in a rat model by direct instillation of amines into the brain are positive for TMA but negative for DMA, but no DMA entry into brain cells is demonstrated in the latter. The generation of aliphatic amines represents only one part of a spectrum of alteration induced by proximal intestinal bacterial enzyme action that occurs in renal failure. It is possible that some bacterial activity is beneficial and that the net clinical result is a balance between the "good" and the "evil" bacterial effects.

Platelet-associated IgG (PAIgG) levels, a useful adjunct for the evaluation of patients with immunologic mediated thrombocytopenia, were obtained in 36 patients with end stage renal disease undergoing maintenance hemodialysis. Twenty-five of the 36 had elevated PAIgG. Nine of the 36 were thrombocytopenic and only 3 of the 9 had elevated PAIgG. Fifteen patients in the group admitted to recent substance abuse. All but one had elevated PAIgG and only one patient was thrombocytopenic. In contrast to patients with idiopathic immune thrombocytopenic purpura (ITP), a direct relationship was not found between PAIgG and total platelet protein (TPP) in the uremic group. It can be concluded that PAIgG values in patients with uremia are difficult to interpret since elevated PAIgG values are found in the majority of uremic patients with normal platelets counts.

Thyroid hormone is known to modulate cell membrane sodium/potassium adenosine triphosphatase (Na/K-ATPase). To determine whether the activity of this enzyme differed in patients with nonthyroidal illness with low levels of circulating thyroid hormones and patients with documented clinical hypothyroidism, we measured Na/K-ATPase activity in red blood cells from patients with hypo- and hyperthyroidism, patients with nonthyroid disease with and without reduced circulating levels of thyroid hormone, and normal subjects. We also assessed whether the activity of this enzyme reflects decreased thyroid hormone action at the cellular level in patients with nonthyroidal illness. Hyperthyroidism was associated with decreased and hypothyroidism with increased erythrocyte Na/K-ATPase activity [142 +/- 24 (+/- SE) and 371 +/- 37 nmol Pi/mg X h; P less than 0.05 and P less than 0.01 compared to normal]. Enzyme activity in cells from patients with nonthyroidal illness and low levels of circulating T3 was significantly higher than that in cells from normal subjects (289 +/- 11 vs. 223 +/- 16 nmol Pi/mg X h; P less than 0.01), but was not significantly different from that in cells from hypothyroid patients. Red cell Na/K-ATPase activity in patients with nonthyroidal illness and normal thyroid function tests (185 +/- 38 nmol Pi/mg X h was indistinguishable from normal values. These data confirm that hyperthyroid patients have decreased red cell Na/K-ATPase activity and provide direct evidence that erythrocyte ATPase activity is increased in hypothyroid patients. The change in enzyme activity in patients with nonthyroidal illness and decreased circulating T3 levels was comparable to that in hypothyroidism. These results suggest that since red cell Na/K-ATPase activity does not distinguish between ill patients with low thyroid function tests and those with hypothyroidism, tissue hypothyroidism may exist in the former group of patients.

Because biotin treatment may lower blood glucose in insulin-dependent diabetes, we chose to study such an effect in non-insulin dependent diabetes. Twenty-six diabetic KK mice, moderately hyperglycemic and insulin resistant, were treated for 10 weeks: 9 animals with 2 mg of biotin/Kg, 8 with 4 mg of biotin/Kg, and 9 with saline (controls). Blood glucose levels, oral glucose tolerance, insulin response to oral glucose, and blood glucose decrease in response to insulin were quantitated. Compared to controls, biotin treatment lowered post-prandial glucose levels, and improved tolerance to glucose and insulin resistance. Serum immunoreactive insulin levels in biotin-treated mice were like the controls.

The first cases of malignant lymphoma with a "myeloma kidney" type of acute renal failure are presented. With appropriate therapy, both patients regained partial renal function; the first after three months of dialysis. It is suggested that the term paraproteinemic nephropathy is preferable to "myeloma kidney."