Search

Platelet function was studied in 11 patients with Raynaud's syndrome and 11 healthy controls. Platelets obtained from patients with Raynaud's syndrome were significantly more responsive to adrenaline, produced more thromboxane A2, and were resistant to prostaglandin inhibitors (prostacyclin and prostaglandin E1) of platelet aggregation. Platelets from control subjects and patients with Raynaud's syndrome were more resistant to prostaglandin inhibitors when reactions were carried out at 27 degrees C rather than at 37 degrees C. Patients with Raynaud's syndrome also had significantly increased plasma concentrations of beta-thromboglobulin, fibrinogen, and circulating platelet aggregates. In an attempt to elicit local platelet responses, the forearms of control subjects and patients with Raynaud's syndrome were cooled in water tanks and platelet function tests performed before and after cooling. No significant difference in the results was observed. The potential role of platelets in the pathogenesis of Raynaud's syndrome is discussed.

Platelet function in alcoholic patients was assessed on admission and during abstinence in hospital. On admission platelets from these patients were significantly less responsive (percentage aggregation and thromboxane A2 release) to conventional in vitro aggregating agents (adrenaline, adenosine diphosphate, and collagen) than platelets from healthy, moderate drinkers. Initially, platelet counts in platelet rich plasma tended to be low and the Simplate II bleeding times frequently prolonged. Platelet aggregation and thromboxane A2 release, however, were inhibited even in patients with normal platelet counts on admission. Platelet aggregation and thromboxane A2 release returned to normal or became hyper-responsive during two to three weeks of abstinence. Platelet counts rose during this period, the largest responses occurring in those patients with the lowest counts on admission. Bleeding times reverted to normal during abstinence and correlated significantly with changes in platelet aggregation, thromboxane A2 release, and platelet count and with the estimated ethanol consumption during the week before admission. Chronic, heavy alcohol ingestion evidently exerts an inhibitory effect on platelet function even in the absence of alcohol in the blood, and this phenomenon is reversible on abstaining. The impaired platelet function, together with the reduced platelet count, may contribute to the bleeding diathesis associated with chronic alcoholism and to the increased incidence and recurrence of gastrointestinal haemorrhage associated with excessive alcohol intake.

In view of the claim that low 25-hydroxyvitamin D (25-OHD) concentrations may contribute to the pathogenesis of bone disease in patients with beta thalassaemia major and iron overload, we have assessed the concentrations of 25-OHD, 1 alpha,25 dihydroxyvitamin D (1 alpha,25(OH)2D), parathyroid hormone, and osteocalcin in such patients. 25-OHD concentrations were significantly lower in patients with thalassaemia major and iron overload than in controls and in some patients were subnormal or undetectable. 1 alpha,25(OH)2D concentrations were, however, normal in all patients and were similar to those in controls. Serum parathyroid hormone and plasma calcium concentrations were also normal and not significantly different from those in controls. Although 25-OHD concentrations increased significantly between January and June, there was no change in 1 alpha,25(OH)2D concentrations. 25-OHD concentrations remained lower than control values, even in June. Parathyroid hormone concentrations fell, but not significantly, between January and June, but calcium concentrations did not alter. Osteocalcin concentrations were normal in all patients except one, who had extremely low concentrations of this protein. The concentration of osteocalcin was not related to 25-OHD or 1 alpha,25(OH)2D concentrations. Thus normal calcium homeostasis is maintained in patients with thalassaemia major despite low or low-normal 25-OHD concentrations; this is probably achieved through the maintenance of normal 1 alpha,25(OH)2D concentrations, which were indistinguishable from those in controls. Normal 1 alpha,25(OH)2D, parathyroid hormone, and osteocalcin concentrations argue against an important role for vitamin D deficiency in the pathogenesis of thalassemia bone disease.

Serum pancreatic isoamylase activities were used to assess exocrine pancreatic function in 39 patients with diabetes mellitus (21 on insulin, 12 on sulphonylureas, and six on biguanides or diet), and the results were compared with serum immunoreactive trypsin concentrations. Thirteen patients had decreased pancreatic isoamylase activity, the insulin-dependent diabetics showing the highest incidence of abnormality. This incidence of abnormality is similar to that previously described for serum immunoreactive trypsin, and the two procedures gave excellent overall correlation (r = 0.9). Our observations offer further evidence that pancreatic exocrine function is impaired in diabetes mellitus. Serum isoamylase determination provides a convenient, inexpensive, and rapid procedure for its detection.

Serum samples obtained from 20 insulin-dependent diabetics (IDD), 23 non-insulin-dependent diabetics (NIDD) and 30 controls were assayed for their pancreatic lipase activity, immunoreactive trypsin concentration and glycosylated haemoglobin (HbA1) respectively. The distribution of serum pancreatic lipase activity in normal subjects and diabetics was nonparametric. The median serum lipase activity in IDDs (86 U/l) was significantly lower that that in controls (131 U/l, p less than 0.002) and NIDDs (126 U/l, p less than 0.001). There was a significant correlation between serum pancreatic lipase activity and serum IRT concentration (r = 0.65, p less than 0.001). Neither pancreatic lipase activity nor IRT was related to HbA1 concentrations. These data show for the first time that serum pancreatic lipase activity is diminished in IDDs.

Shortened red cell survival has a role in the anaemia of rheumatoid arthritis (RA), but direct measurement of it is difficult. Glycosylated haemoglobin (HbA1) provides an index of red cell life span in normoglycaemic patients, because glycosylation depends on both the concentration of blood glucose and the duration of erythrocyte survival. HbA1 was significantly lower in 30 patients with RA (5.6 +/- 0.7%, mean +/- SD) than in 15 healthy controls (7.3 +/- 0.7%) and 14 patients with osteoarthritis (7.4 +/- 0.7%, p less than 0.001). HbA1 was depressed less in active RA than during remission, which is consistent with diminished red cell production in active RA. These data on HbA1 confirm that shortened red cell survival is common in RA, and point to diminished red cell production in active disease. Determination of HbA1 should prove to be of clinical value in the assessment of normoglycaemic patients with RA but is an inadequate index of glucose homoeostasis in diabetics with RA.

A patient with Graves's disease with acute progressive exophthalmos and pretibial myxoedema was treated twice with plasmapheresis. Two weeks after the first treatment the symptoms recurred, but 20 weeks after the second treatment the exophthalmos was much improved and the pretibial myxoedema had disappeared. Analysis of sequential serum IgG concentrations and the thyroid-stimulating immunoglobulin index suggested that the two conditions were caused by specific IgGs. The results suggest that plasmapheresis has a useful place in the treatment of acute and rapidly progressive ophthalmopathy and pretibial myxoedema in patients with Graves's disease.

Nine patients with acute leukaemia developed a complex syndrome of hypocalcaemia and hypomagnesaemia during treatment. These metabolic abnormalities developed rapidly in some patients and gave rise to acute symptoms. Immunoreactive parathormone concentrations in these patients were found to be either absolutely or inappropriately low. Hypomagnesaemia and the action of chemotherapeutic agents, especially adriamycin or cytarabine, or both may have contributed to the pathogenesis of this syndrome.

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.

Serum immunoreactive trypsin (IRT) concentrations were measured blind in sera from 33 patients with cystic fibrosis and in 32 age-matched controls. Thirty-two patients had abnormal trypsin concentrations. In 30 of these patients the level of IRT was very low whereas in the other two (the youngest of the group) it was extremely high. All 30 patients with low IRT concentrations had clinical or biochemical evidence of malabsorption. Serum IRT concentration may thus be a useful diagnostic test for cystic fibrosis. In view of the recent observation that neonates with cystic fibrosis consistently have raised IRT concentrations, and the fact that the youngest two patients in our series also had markedly increased IRT, it would appear that the initial elevation of IRT reflects early damage to the pancreas with release of enzyme/zymogen; this is thereafter superseded by a progressive destruction of the pancreas resulting in low IRT concentrations in adults with cystic fibrosis.

To assess the exocrine pancreatic function in beta-thalassemia major with iron overload, serum immunoreactive trypsin (IRT) was measured in 38 patients with this condition. In 23 (60%) patients' IRT was abnormal: it was subnormal in 16 patients and supranormal in seven. Whereas subnormal IRT concentrations were more frequent in patients of more than 12 years old, supranormal IRT concentrations were more frequent in younger patients. These data provide the first antemortem evidence of exocrine pancreatic damage in this condition. They also suggest that this acinar cell damage is initially associated with a rise in IRT which is followed by a fall in the serum concentration of this enzyme.

A propos de 2 observations chez des femmes asiatiques, vegetariennes, de niveau socio-economique eleve. Dans les 2 cas des douleurs donnent l'occasion de diagnostiquer des fractures passees inapercues, et une osteomalacie. Le traitement comportant de la vitamine D est efficace

Ketoconazole, a potent antifungal agent, inhibits adrenal steroidogenesis in normal subjects during short term treatment. Since this drug is used in the long term prophylaxis of fungal infections in patients with haematological malignancies, we have investigated whether such patients have evidence of adrenocortical suppression. Six patients on long term prophylaxis with ketoconazole were given tetracosactrin stimulation tests. All patients had high basal cortisol concentrations, which increased further after administration of 25 IU of tetracosactrin. It is concluded that leukaemic patients receiving long term ketoconazole treatment do not have adrenocortical suppression. They may, in fact, have hyperstimulated adrenocortical function due to stress and hypovolaemia.

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.