V. Fonseca

Intraplatelet serotonin in patients with diabetes mellitus and peripheral vascular disease

Abstract Intraplatelet serotonin (5‐HT) content was determined in 23 patients with type I (insulin‐dependent) diabetes mellitus (IDDM), 23 patients with type II (non‐insulin‐dependent) diabetes mellitus (NIDDM), 29 patients with peripheral vascular disease (PVD) and 34 age‐matched normal subjects. Intraplatelet 5‐HT content in normal subjects showed an age‐related decline (r=–0·45; P < 0·008), as has been previously demonstrated. The median 5‐HT content in platelets of the young normal subjects was 4·36 (range: 3·62–6·79) nmol 10‐9platelets, while that in the elderly normal subjects was 3·87 (range: 2·8–6·0) nmol 10‐9platelets and that in young+elderly subjects was 4·05 (range: 2·8–6·8) nmol 10‐9platelets. The median intraplatelet 5‐HT content was significantly lower (P < 0·002) in IDDM patients: 3·0 (range 1·3–6·3), NIDDM patients: 2·5 (range 1·7–5·8), PVD patients: 2·42 (range 0·94–4·98) nmol 10‐9platelets than that in all young+elderly healthy subjects. The presence of hypertension in DM patients caused a small but significant (P < 0·05) decrease in intraplatelet 5‐HT content, whilst its presence had no effect in PVD patients. In a smaller study, it was established that NIDDM and PVD patients have significantly (P < 0·002) greater plasma 5‐HT concentrations than controls. Insulin‐dependent diabetes mellitus patients had greater plasma 5‐HT concentrations but this did not achieve statistical significance despite a 66% increment in its value. We conclude that the diminished 5‐HT content in platelets and the increased plasma levels may reflect enhanced release of 5‐HT by hyperactive platelets. This increase in plasma 5‐HT may contribute to the pathogenesis of atherosclerosis and vasospasm.

Vitamin D deficiency and low osteocalcin concentrations in anorexia nervosa.

The calcium, vitamin D, and osteocalcin concentrations were investigated in 17 patients with anorexia nervosa. Serum 25-hydroxyvitamin D (25 OHD) concentrations below normal were observed in 15 (88%); only two patients has serum 1,25 dihydroxycholecalciferol (1,25(OH)2D) concentrations below normal. Serum parathyroid hormone (PTH) concentration was also normal in all except these two patients. Serum osteocalcin concentration was below normal in seven of 14 patients. Although a low concentration of serum 25 OHD is common in patients with anorexia nervosa in the United Kingdom, 1,25(OH)2D concentrations are usually normal. Hypovitaminosis D with secondary hyperparathyroidism is relatively uncommon. The subnormal osteocalcin concentrations observed in these patients probably reflect diminished osteoblastic activity, which may contribute to their osteopenia.

Bone Density and Cortical Thickness in Nutritional Vitamin D Deficiency: Effect of Secondary Hyperparathyroidism

Measurements of bone mineral index, mean metacarpal cortical thickness, plasma calcium, alkaline phosphatase and serum 25-hydroxyvitamin D and parathyroid hormone concentrations were carried out in 39 Asian vegetarian patients with hypovitaminosis D. It was concluded that PTH is probably the major determinant of osteopenia in patients with osteomalacia and secondary hyperparathyroidism; and that the presence of secondary hyperparathyroidism in association with hypovitaminosis D should be an absolute indication for vitamin D supplementation even in asymptomatic patients.

Plasma histamine concentrations are elevated in patients with diabetes mellitus and peripheral vascular diasease

Previous work has shown that plasma and tissue concentrations of histamine are elevated in rats with experimental diabetes mellitus and that leucocytes and platelets from patients with peripheral vascular disease have a higher histamine content than those from controls. In the present study, we have measured: (a) plasma histamine concentrations; (b) leucocyte and platelet histidine decarboxylase (the enzyme responsible for the biosynthesis of histamine) in patients with diabetes mellitus (Types I and II) and peripheral vascular disease; and (c) platelet and leucocyte histamine content. Plasma histamine concentration was significantly higher in patients with diabetes and peripheral vascular disease respectively than that in age-matched controls. Leucocyte histidine decarboxylase activity in diabetic and peripheral vascular disease patients was similar to that in controls, while platelets had no histidine decarboxylase activity. The leucocyte and platelet content of histamine were greater in patients with peripheral vascular disease than those in controls, but they were not altered in diabetic patients. There was no correlation between plasma histamine concentration, leucocyte and platelet histamine content, and histidine decarboxylase activity. We conclude that plasma histamine is elevated in diabetics and in patients with peripheral vascular disease and that platelet and leucocyte histamine content is increased in the latter. This increase in platelet and leucocyte histamine content is not due to an increase in histidine decarboxylase activity of these cells. The increase in plasma and cellular histamine content may contribute to the pathogenesis of increased endothelial permeability in diabetes and to the pathogenesis of intimal damage in atherosclerosis.

Can urinary thyroid hormone loss cause hypothyroidism

Four patients presented with nephrotic syndrome associated with hypothyroidism; none had thyroid antibodies. Hypothyroidism resolved on remission of nephrotic syndrome in two patients; thyroxine (T4) replacement was ineffective during periods of gross proteinuria in another, and the fourth had had normal thyroid function a year before presentation. Urinary T4 excretion was measured in ten further patients with proteinuria. It was detectable in the urine in five, who had significantly lower serum free T4 (8.5 [95% confidence interval 5.8-11.2] vs 13.9 [11.1-16.7] pmol/l; p less than 0.01) and free triiodothyronine (3.1 [2.2-4.0] vs 4.9 [3.8-6.0] pmol/l; p less than 0.01) concentrations than the five patients without detectable urinary T4.

Plasma histamine in patients with chronic renal failure and nephrotic syndrome.

Plasma histamine concentrations were measured using a commercially available monoclonal antibody radioimmunoassay in 38 patients with nephrotic syndrome, end stage renal failure, those receiving haemodialysis, and those receiving continuous ambulatory peritoneal dialysis to determine whether histamine may mediate damage to glomerular capillaries and arterial endothelium. Plasma histamine concentrations were significantly increased in all four patient groups when compared with those of controls and were the highest in two patients with pruritus. Raised plasma histamine concentrations in such patients are consistent with the hypothesis that histamine may contribute to the damage to glomerular capillaries and to arterial endothelium. These effects may be relevant to the pathogenesis of glomerular disease and atherosclerosis. Histamine may also contribute to the pathogenesis of pruritus in patients with chronic renal failure.

Splenic abscess in patients on hemodialysis.

We describe two patients on hemodialysis who developed staphylococcal splenic abscesses. Both patients previously had staphylococcal septicemia secondary to infection at the dialysis access site. We postulate that access-site infections may predispose hemodialysis patients to splenic abscess, and that these patients should be investigated for a splenic abscess if they should develop unexplained fever.

PLASMA CREATININE AND CREATININE CLEARANCE IN NUTRITIONAL OSTEOMALACIA

To confirm recent observations that some vitamin D deficient osteomalacic patients had low plasma creatinine concentrations, low urinary creatinine excretion, and a paradoxically low creatinine clearance, and whether these changes were due to vitamin D deficiency per se, these measurements were made in patients before and after vitamin D supplementation. The pretreatment levels were also compared with those in healthy controls and in non-osteomalacic patients without renal disease. The above changes were confirmed. After treatment with vitamin D, plasma creatinine concentrations rose, but urinary creatinine excretion and creatinine clearance did not alter. These data indicate the limitation of creatinine clearance as an index of renal function in vegetarian osteomalacic patients. Furthermore, they demonstrate the effect of vitamin D deficiency and its reversal on plasma creatinine concentrations.

Hypoalbuminaemic hyponatraemia: a new syndrome?

Six patients with severe hyponatraemia had neurological features of hyponatraemia and pronounced hypoalbuminaemia. All had biochemical features typical of the syndrome of inappropriate secretion of antidiuretic hormone with low serum osmolality and an inappropriately high urinary osmolality. All were given infusions of whole plasma or albumin solution, or both, to restore their plasma albumin concentrations to normal, which led to a dramatic increase in plasma sodium concentrations and serum osmolality, with a concomitant fall in urinary osmolality in all patients. Neurological features were reversed in four patients. It is suggested that severe hypoalbuminaemia is an important cause of appreciable hyponatraemia; infusions of plasma and albumin in such patients may reverse the biochemical and clinical features and should form the basis of management.

Insulin receptor antibodies causing steroid responsive diabetes mellitus in a patient with myositis.

tenderness, and diffuse vitiligo. Haemoglobin concentration was 10 g/dl and leucocyte count 17X 109/1 (39% neutrophils, 16% lymphocytes, 3% monocytes, 42% eosinophils). Plasma urea, electrolyte, and creatinine concentrations were normal, as were the results of liver function tests. Creatine kinase activity was 1621 IU/l. She had glycosuria, and a random blood glucose estimation yielded 10 mmol/l (180 mg/100 ml). Rheumatoid factor and antinuclear and anti-DNA antibodies were absent. Electromyography and muscle biopsy confirmed polymyositis. A glucose tolerance test showed mild diabetes mellitus with hyperinsulinaemia (table). The patient was treated with oral prednisolone 40 mg daily, and within one week her muscle power had improved dramatically. Results of a repeat glucose tolerance test and a fasting immunoreactive insulin concentration were normal. The remission was maintained with 20 mg prednisolone given on alternate days. Six months later the patient stopped the prednisolone and a relapse of polymyositis and glucose intolerance ensued. Reintroduction of prednisolone again induced and maintained remission. Serum taken during the active phase of the illness was tested for its ability to inhibit the binding of insulin to insulin receptors in human placental membranes, as follows: 17, 23, 34, 43, and 49% inhibition was found at dilutions of one in 200, 100, 40, 20, and 10 respectively. IgG prepared from the patients serum by protein A Sepharose chromatography was tested in the adipocyte lipogenesis system.3 The stimulatory effect of the patients IgG was less than that of control IgG (451% v 672% stimulation at 25 mg IgG/l).