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Biomedical subjects

I Raz

Publications and source records attributed to I Raz.

At least 91 records · Page 5Linked to original sources

Low urinary chiro-inositol excretion in non-insulin-dependent diabetes mellitus.

BACKGROUND AND METHODS: Inositol is a major component of the intracellular mediators of insulin action. To investigate the possible role of altered inositol metabolism in non-insulin-dependent diabetes mellitus (NIDDM), we used gas chromatography and mass spectrometry to measure the myo-inositol and chiro-inositol content of urine specimens from normal subjects and patients with NIDDM: The study subjects were whites, blacks, and Pima Indians. The type of inositol and its concentration in insulin-mediator preparations from muscle-biopsy specimens from normal subjects and diabetic patients were also determined. RESULTS: The urinary excretion of chiro-inositol was much lower in the patients with NIDDM (mean [+/- SE], 1.8 +/- 0.8 mumol per day) than in the normal subjects (mean, 84.9 +/- 26.9 mumol per day; P less than 0.01). In contrast, the mean urinary myo-inositol excretion was higher in the diabetic patients than in the normal subjects (444 +/- 135 vs. 176 +/- 46 mumol per day; P less than 0.05). There was no correlation between chiro-inositol excretion and the age, sex, or weight of the diabetic patients, nor was there any correlation between urinary chiro-inositol and myo-inositol excretion in either group. The results were similar in a primate model of NIDDM, and chiro-inositol excretion was decreased to a lesser extent in animals with prediabetic insulin resistance. chiro-Inositol was undetectable in insulin-mediator preparations from muscle-biopsy samples obtained from patients with NIDDM: Similar preparations from normal subjects contained substantial amounts of chiro-inositol. Furthermore, the chiro-inositol content of such preparations increased after the administration of insulin during euglycemic-hyperinsulinemic-clamp studies in normal subjects but not in patients with NIDDM: CONCLUSIONS: NIDDM is associated with decreased chiro-inositol excretion and decreased chiro-inositol content in muscle. These abnormalities seem to reflect the presence of insulin resistance in NIDDM:

Age Factors↗

Autoimmune hemolytic anemia in Gaucher's disease.

A 23-year-old Ashkenazi woman with Gaucher's disease developed Coombs-positive warm-type autoimmune hemolytic anemia. Treatment with high-dose steroids resulted in complete remission within 2 weeks. Study of an additional 72 patients with Gaucher's disease revealed another case of Coombs-positive warm-type autoimmune hemolytic anemia; other autoimmune disorders were found in 17 of these patients. The possible association of Coombs-positive hemolytic anemia and Gaucher's disease is discussed.

Adult↗

Skeletal muscle glycogen synthase activity in subjects with non-insulin-dependent diabetes mellitus after glyburide therapy.

Sulfonylureas are used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) largely because of their ability to enhance insulin secretion and possibly to potentiate insulin action. In this study, we investigated the effects of chronic glyburide treatment on glycogen synthase activity determined in skeletal muscle biopsies taken during euglycemic hyperinsulinemic clamps in nine Pima Indians with NIDDM. Insulin was infused at the rate of 40 mU/m2/min (low dose) followed by 400 mU/m2/min (high dose). Compared with the fasting value, the mean glycogen synthase activity assayed at low glucose-6-phosphate (G6P) concentration (active glycogen synthase) showed no significant changes during insulin infusion before glyburide treatment. After glyburide treatment, the mean active glycogen synthase increased by 39% (P less than .05) above the fasting value during the high-dose insulin infusion. Total glycogen synthase activity assayed at high G6P concentration did not change after glyburide treatment. Changes of insulin-stimulated active glycogen synthase associated with glyburide treatment correlated with changes in total body glucose disposal rates (r = .70, P less than .05) during euglycemic clamps. We conclude that glyburide treatment of subjects with NIDDM is associated with an increase in insulin action in vivo and concomitantly with improved insulin action on skeletal muscle glycogen synthase.

Adult↗

Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ.

Reduced oxidation of fat leading to a positive fat balance could be a factor in the development of obesity. Twenty-four-hour respiratory quotient (RQ) was measured in 152 nondiabetic Pima Indians fed a weight-maintenance diet [87 males and 65 females; 27 +/- 6 yr (mean +/- SD); 93.9 +/- 22.9 kg; 32 +/- 9% fat]. Twenty-four-hour RQ varied from 0.799 to 0.903. Prior change in body weight, 24-h energy balance, sex, and percent body fat explained 18% of the variance in 24-h RQ (P less than 0.001). In a subgroup of 66 siblings from 28 families, family membership explained 28% of the remaining variance in 24-h RQ (P less than 0.05). In 111 subjects for whom follow-up data (25 +/- 11 mo) were available, 24-h RQ was correlated with subsequent changes in body weight and fat mass (r = 0.27, P less than 0.01 and r = 0.19, P less than 0.05, respectively). Subjects with higher 24-h RQ (90th percentile) independent of 24-h energy expenditure were at 2.5 times higher risk of gaining greater than or equal to 5 kg body weight than those with lower 24-h RQ (10th percentile). We conclude that in Pima Indians fed a standard diet 1) family membership is the principal determinant of the ratio of fat to carbohydrate oxidation, and 2) a low ratio of fat to carbohydrate oxidation is associated with subsequent weight gain independent of low energy expenditure and may contribute to the familial aggregation of obesity.

Adult↗

Effects of human diabetic serum on the in vitro development of early somite rat embryos.

High levels of glucose, beta-hydroxybutyrate (B-HOB), and acetoacetate are known to have embryotoxic and teratogenic effects on rat embryos in culture, especially when added concomitantly to the culture medium. We studied the effects of human serum from different types of diabetes mellitus on the in vitro development of 10 1/2-day-old rat embryos cultured for 48 hours. We used serum from type I diabetes with and without ketoacidosis and type II diabetes either untreated or treated with insulin or with daonil. Type I diabetes without ketoacidosis increased the rate of malformations to 27% vs. 11% in controls. Serum from type I diabetes with ketoacidosis further increased the malformation rate to 44%. The rate of malformations induced by serum of type II diabetes was dependent on the treatment. It was relatively low among embryos cultured on serum from untreated (16%) or treated with daonil (19%) and rose to 27% among embryos cultured on serum from type II diabetes treated with insulin. No significant correlation was found between the rate of malformations and the concentrations of glucose, B-HOB, acetoacetate, and HbA1c in all diabetic sera except serum from type I diabetes with ketoacidosis. We may therefore conclude that for most types of diabetes in humans, neither the high blood glucose concentrations nor the high levels of ketone bodies seem to be the main reason for the high rate of malformations. However, we used cultured rat embryos, and the effects on the human embryo may be different. The results of studies on various experimental animal models in diabetes teratogenicity seem to have only partial relevance to the human situation.

Animals↗

Pulmonary manifestations in Behçet's syndrome.

Among 72 patients with Behçet's syndrome, seven had pulmonary vascular involvement. Additional data from 42 cases in the literature are discussed. Recurrent episodes of dyspnea, cough, chest pain, and hemoptysis were the primary clinical signs, mainly in young men, appearing 3.6 years after the first manifestation of Behçet's syndrome. Fever, elevated ESR, and anemia were common, and chest x-ray films showed pulmonary infiltrates, pleural effusions, and prominent pulmonary arteries. Ventilation-perfusion scans showed perfusion defects even when chest x-ray films were normal. Pulmonary artery aneurysms were seen in 7/13 in whom angiography was done. Of 42 patients, 16 died, 15 from fatal pulmonary hemorrhage, 80 percent within two years from the development of pulmonary disease. Histopathologic study results showed vasculitis of pulmonary vessels of various sizes, leading to thrombosis, destruction of the elastic laminae, aneurysms, and arteriobronchial fistula. In addition, pulmonary emboli and the aphthous lesion of the tracheobronchial tree may aid the clinical picture. Anticoagulant therapy may be hazardous in patients with aneurysmal dilatation of the pulmonary vascular tree, and the beneficial effect of corticosteroid therapy is discussed. Pulmonary vasculitis in Behçet's syndrome is a unique clinical and pathologic picture, differing from other vasculitides affecting the lung, presents a major threat to the patient's life.

Adult↗

The influence of zinc supplementation on glucose homeostasis in NIDDM.

Decreased serum zinc levels and hyperzincuria occur in some non-insulin dependent diabetic subjects (NIDDM). Zinc deficiency was demonstrated in various tissues of animal models for NIDDM. Serum zinc and 24-hr urine zinc of subjects with NIDDM were compared with that of age- and sex-matched healthy volunteers. Zincuria was significantly increased in the diabetic group. Thirteen diabetic subjects with hyperzincuria and hypozincemia were supplemented with zinc sulfate 220 mg x 3/day for 7-8 weeks. At the end of the study, glucose disposal (evaluated by kg) decreased significantly from 0.562 +/- 0.03 to 0.414 +/- 0.05 (p less than 0.05) and fasting glucose and fructosamine were significantly increased from 177 +/- 10 mg/dl to 207 +/- 15 mg/dl (p less than 0.05) and from 2.7 +/- 0.2% to 3.2 +/- 0.28% (p less than 0.05), respectively. T-lymphocyte response to phytohemagglutinin was increased significantly. We conclude that zinc supplementation to NIDD patients with hypozincemia and hyperzincemia might aggravate their glucose intolerance. More accurate methods to assess zinc deficiency in NIDD patients is needed to justify the supplementation of zinc in these patients.

Blood Glucose↗

Trace elements in blood cells of diabetic subjects.

The majority of zinc, copper and magnesium is either intracellular or associated with the bones. It is therefore unlikely that the plasma concentration of these trace elements will reflect their whole body content. Blood cells might be more representative of lean tissue and are also easy to obtain. The concentration of zinc, copper and magnesium was measured in the leukocytes and hemoglobin of 42 subjects with non insulin dependent diabetes mellitus (NIDDM) and in 22 subjects with insulin dependent diabetes mellitus (IDDM) and was compared with that of 44 age-matched healthy volunteers. Zinc was found to be deficient in the serum (p less than 0.001), leukocyte (p less than 0.001) and hemoglobin (p less than 0.05) of the IDDM subjects, while copper and magnesium were increased in the serum, leukocytes and hemoglobin of the IDDM subjects (p less than 0.001). There was no zinc deficiency in the leukocytes of NIDD subjects. These results are opposite to the findings on zinc concentration in various tissue of animal models for IDDM and NIDDM and with our present knowledge on zinc status in IDDM and NIDDM subjects. Thus, we conclude that the concentration of zinc in blood cells of diabetic subjects might not reflect its concentration in various tissues.

Adult↗

Glibenclamide causing thrombocytopenia and bleeding tendency: case reports and a review of the literature.

We described two patients with severe thrombocytopenia and bleeding tendency related to treatment with glibenclamide (short-acting sulfonylurea). To the best of our knowledge, thrombocytopenic purpura associated with this medication has been reported only twice previously. We suggest that platelet count should be carried out early after initiating glibenclamide treatment and every 3 months thereafter.

Diabetes Mellitus, Type 2↗

Reduced negative surface charge on arterial endothelium of diabetic rats.

Cationized ferritin binding was used to measure negative surface charge on endothelium of large arteries in streptozotocin-induced diabetic rats and normal control rats. The negative charge was significantly lower in the diabetic animals (p less than 0.01). This change, possibly related to glycosylation, may lead to altered vascular permeability and may be of importance in the vascular pathology of diabetes.

Animals↗

Altered tissue content of trace metals in diabetic hyperinsulinaemic sand rats (Psammomys obesus).

The concentrations of zinc, copper, and chromium in liver, kidney, muscle, bone and serum from control normoinsulinaemic and hyperinsulinaemic sand rats (Psammomys obesus) and from untreated spontaneously hyperinsulinaemic-hyperglycaemic sand rats were compared. A chronic hyperinsulinaemic-hyperglycaemic state was associated with a significant reduction (p less than 0.01) of zinc concentration in the liver, kidney and muscle but an elevation of zinc content in bone and of chromium in the liver. A hyperinsulinaemic-nor-moglycaemic state was not associated with similar changes in zinc concentration in the liver, kidney, muscle and bone. We conclude that in hyperinsulinaemic-hyperglycaemic sand rats there is a tendency to zinc depletion in several tissues. This depletion is not solely the result of a hyperinsulinaemic state but may be related to accompanying hyperglycaemia.

Animals↗

Atrioventricular block complicating acute streptococcal tonsillitis.

A 38 year old woman presented with severe weakness, high fever, and sore throat. Physical examination showed follicular tonsillitis and bradycardia caused by a atrioventricular block. Within 24 hours a normal sinus rhythm was regained but slight transient ST-T changes compatible with myocarditis were evident. Throat culture grew Streptococcus haemolyticus group A.

Acute Disease↗

Amiodarone pulmonary toxicity presenting as a solitary lung mass.

Following treatment with amiodarone, a patient developed weight loss, fatigue and severe myopathy, without respiratory symptoms. A solitary lung infiltrate, impaired thyroid and liver function tests, and leukocytosis were evident. Biopsies from the lung lesion, liver, and bone marrow revealed foam cells. All these signs and symptoms subsided following cessation of amiodarone therapy. It is demonstrated that amiodarone may induce a localized lung lesion rather than diffuse pulmonary disease.

Aged↗

Effect of hyperglycemia on pain perception and on efficacy of morphine analgesia in rats.

The effect exerted by different hyperglycemic states on the pain threshold and on the analgesic potential of morphine was studied in male Sabra rats with the hot plate device. Hyperglycemia induced by an intraperitoneal injection of 0.014 mol/kg glucose or an acute or chronic diabetic state induced by streptozocin injection did not significantly alter the pain threshold. However, states of acute and chronic diabetes markedly blunted the analgesic effect of morphine (5 mg/kg). Sabra rats maintained on a cocktail of glucose-saccharin, thought to activate the release of endogenous opioids, demonstrated an increased pain threshold and rapidly developed resistance to the analgesic effect of morphine. Previous studies have shown that glucose in high concentration may interfere with the interaction of morphine on the opiate receptor. The influence of the diabetic state on beta-endorphin synthesis and concentration in the central nervous system is another factor that might change pain perception in diabetes. We propose that in diabetes, generally, the pain threshold is adequately maintained, despite the antagonistic effect of glucose, partly due to a compensatory increased secretion of endogenous opioid peptides. We hypothesize that in patients with chronic painful diabetic neuropathy, these normal analgesic response mechanisms may be overwhelmed either by an excess of nociceptive impulses from diseased peripheral nerves or conceivably by a failure of endogenous opioid secretory response to the hyperglycemia.

Action Potentials↗

Influence of small-group education sessions on glucose homeostasis in NIDDM.

In patients with non-insulin-dependent diabetes mellitus (NIDDM), the influence of knowledge about their disease on the treatment and control of the disease is not clear. We evaluated the efficacy of educational group meetings with NIDDM patients on improving their knowledge of the disease and on disease management. Fifty-one NIDDM patients were randomly assigned to either intervention or control groups. The intervention group participated in courses of three weekly lessons presented by a physician, nurse, and dietitian once every 4 mo. The intervention and control groups were also followed once every 2 mo in the clinic by the same staff. Medical treatment remained unchanged during the study. After a 12-mo follow-up of the intervention group, no significant improvement in their knowledge of diabetes could be demonstrated. However, mean fasting and postprandial blood glucose levels and HbA1c improved significantly in comparison with the control group. The same tendency was evident with the weight and lipoprotein profile. We conclude that educational group therapy can improve diabetes control in patients with NIDDM.

Adult↗