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Biomedical subjects

M Koffler

Publications and source records attributed to M Koffler.

At least 19 recordsLinked to original sources
PubMed2002

Rheological determinants of red blood cell aggregation in diabetic patients in relation to their metabolic control.

AIMS: To determine whether increased red blood cell adhesiveness/aggregation in diabetic patients is related to the extent of their metabolic control. METHODS: We measured erythrocyte adhesiveness/aggregation in a group of 85 adult patients with diabetes mellitus by using citrated venous whole blood and a simple slide test. The erythrocyte adhesiveness/aggregation was determined by measuring the size of the spaces that are formed between the aggregated erythrocytes. We divided the patients into those with either low or high erythrocyte adhesiveness/aggregation values. RESULTS: The erythrocyte adhesiveness/aggregation values of the two groups differed significantly in terms of their fibrinogen concentration, erythrocyte sedimentation rate, high sensitive C-reactive protein (CRP), total cholesterol and triglyceride concentrations. There was no difference between the two groups regarding the concentrations of HbA(1c). Logistic regression was applied to construct a model to predict the belonging of a patient in the low or high erythrocyte adhesiveness/aggregation group. A linear regression was applied to construct a model to predict the erythrocyte adhesiveness/aggregation values. Both models turned out to include gender, age, fibrinogen, triglyceride, retinopathy, coronary artery disease and age and gender interaction. Neither HbA(1c) nor CRP entered the models. CONCLUSIONS: The degree of erythrocyte adhesiveness/aggregation and several variables of the acute-phase response in patients with diabetes mellitus are not directly related to the degree of metabolic control as evaluated by means of HbA(1c) concentration. Diabetic patients might benefit from rheological or anti-inflammatory interventions regardless of their metabolic control.

Acute-Phase Proteins↗
PubMed2001

The multiplicity of atherosclerotic risk factors corresponds to the appearance of increased leukocyte count in the peripheral blood: relevance to the pathogenesis of the disease.

White blood cells may have a role in the aetiopathogenesis of atherosclerosis disease in patients with risk factors for this disease. We examined the white blood cell count in a group of 331 patients and controls of the same age group (139 women and 192 men), the numbers of individuals with no, one, two or more atherosclerotic risk factors being 29, 47, 35 and 28 for women and 50, 45, 68 and 29 for men, respectively. The risk factors included were hypertension, hyperlipidaemia, current smoking and diabetes mellitus. A stepwise increment in the white blood cell count was found in both women and men, the respective values for no, one, two or more risk factors being 6.3 +/- 1.5, 7.6 +/- 1.9, 7.5 +/- 1.8, 7.3 +/- 1.4 and 6.6 +/- 1.6, 6.9 +/- 1.9, 7.4 +/- 2.1, 8.1 +/- 2.6 (absolute number of cells per cm x 103). The one-way analysis variance was found to be significant for both women (P=0.01) and men (P=0.01), as well as the entire cohort (P=0.03). We conclude that the multiplicity of risk factors for atherosclerosis is associated with the appearance of an increased number of white blood cells in the peripheral blood. These findings might represent an enhanced inflammatory response in these individuals and at the same time reveal a potential harmful role of the cells in the aetiopathogenesis of the disease.

Analysis of Variance↗
PubMed1993

The Gulf War and diabetes mellitus.

The Gulf war was a traumatic and stressful event for the inhabitants of Tel-Aviv and vicinity. The entire population changed its way-of-life. In order to evaluate the influence of the war stress on glucose control, we reviewed the charts of all diabetic patients attending the outpatient clinics at the Tel-Aviv Medical Centre, whose weight and glycated haemoglobin was determined between 15.1.91 and 2.5.91 (the war period), with comparative measurements within 4 1/2 months both before and after these dates. Sixty-six patients with non-insulin dependent diabetes mellitus (NIDDM) and 16 with insulin-dependent diabetes mellitus (IDDM) were examined. During the war, their glycated haemoglobin increased by 10.1 to 10.9% and from 9.6 to 10.2%, respectively. Weight increased from 76.1 to 77.5 kg in the NIDDM and from 63.2 to 64.7 kg in the IDDM patients. Both measurements returned to baseline after the war. No correlation was found between the changes in glycated haemoglobin and weight.

Adult↗
PubMed1992

Effect of high carbohydrate intake on hyperglycemia, islet function, and plasma lipoproteins in NIDDM.

OBJECTIVE: To study effects of high carbohydrate intake on hyperglycemia, islet functions, and plasma lipoproteins in patients with NIDDM. RESEARCH DESIGN AND METHODS: An attempt was made to induce hyperglycemia in 10 men with NIDDM by feeding them an isocaloric high-carbohydrate diet (65% of energy as simple carbohydrates [31% as glucose] and 20% as fat) for 28 days in a metabolic ward. Response to the high-carbohydrate diet was compared with that of feeding a diet rich in monounsaturated fat (45% of energy as fat [31% as monounsaturated fat] and 38% as carbohydrates) for 28 days in a cross-over manner. Islet functions were assessed by evaluating plasma glucose, insulin, C-peptide and glucagon responses to standard meal tolerance tests on days 0, 14, 21, and 28 of each dietary period. Fasting plasma lipoproteins were determined during the last week of each dietary period. RESULTS: The high-carbohydrate diet caused significant but modest accentuation of hyperglycemia, particularly in patients with moderately severe diabetes mellitus, whereas no change was observed with the high-monounsaturated fatty-acid diet. Accentuation of hyperglycemia was accompanied by an increase in plasma glucagon levels, but no significant change in insulin and C-peptide responses. In 1 patient, feeding the high-carbohydrate diet for 68 days produced marked hyperglycemia and caused definite suppression of insulin and C-peptide responses along with an increase in glucagon levels. Compared with the high-monounsaturated fat diet, the high-carbohydrate diet also raised plasma triglyceride and VLDL cholesterol concentrations. CONCLUSIONS: High-carbohydrate diets may cause accentuation of hyperglycemia and a rise in plasma glucagon levels in NIDDM patients. High-carbohydrate diets also adversely affect lipoproteins and therefore may not be desirable in all NIDDM patients.

Blood Glucose↗
PubMed1991

Immunobiological consequence of regulation of insulin receptor on alloactivated lymphocytes in normal and obese subjects.

Acute manipulations of insulin in vivo regulate the display of insulin receptors induced on activated T lymphocytes after presentation of alloantigen. This study explored the immunobiological consequences of regulation of insulin-receptor display by acute manipulations of insulin achieved during the hyperinsulinemic-euglycemic clamp in healthy normal individuals and obese subjects. T lymphocytes were isolated at 0, 1, and 4 h of hyperinsulinemia from seven normal volunteers and seven obese individuals and studied for their capacity to 1) synthesize a complement of insulin receptors on cell membrane, 2) respond to alloantigen in the mixed-lymphocyte culture (an immunologic activity unrelated to manipulations in insulin concentrations in complete medium), and 3) respond to the lymphocyte-mediated cytotoxicity reaction (an immunologic activity known to be modulated by insulin). In the face of a reduction in receptor numbers to 25% of baseline in normal individuals, alloreactivity in the mixed-lymphocyte culture was not affected (95 +/- 9% of time 0 after 4 h of hyperinsulinemia), whereas lymphocyte-mediated cytotoxicity fell from 14 +/- 4 at time 0 to 2 +/- 2% sp Cr release (P less than 0.02). Hyperinsulinemia achieved by the clamp in seven obese subjects did not alter the synthesis of insulin receptors on cell membrane after presentation of alloantigen. In the absence of further reduction of insulin-receptor membrane display, neither the mixed-lymphocyte culture nor lymphocyte-mediated cytotoxicity reaction was affected. It is concluded that those immunologic activities of lymphocytes that can be modulated by insulin are affected by regulation of insulin-receptor display on activated lymphocytes. Therefore, receptor regulation is not effete but carries significant immunologic consequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Blurred vision: an overlooked initial presenting symptom of insulin-dependent diabetes mellitus.

Blurred vision, a well-known complication of uncontrolled diabetes mellitus, is occasionally overlooked as the first and only presenting symptom of type I diabetes mellitus. In this report we describe six type I diabetic patients whose first and only symptom of the disease was blurred vision, as documented by increased glycosylated hemoglobin. Institution of therapy was delayed until the classical symptoms of diabetes mellitus appeared.

Adult↗
PubMed1989

Isolated symptomatic peripheral neuropathy in type 1 insulin-dependent diabetes mellitus.

Diabetic neuropathy is probably the most frequent of the chronic complications of diabetes, and is usually found in association with diabetic retinopathy and/or nephropathy. We report seven patients with long-standing insulin-dependent diabetes mellitus in whom symptomatic peripheral neuropathy was the first and only documented complication. The diagnosis of peripheral symmetrical neuropathy was based on the presence of symptoms and abnormal physical findings, confirmed with abnormal electrophysiological and/or vibratory and thermal threshold measurements. Diabetic retinopathy and nephropathy were absent. We conclude that in some type 1 insulin-dependent diabetic patients, similar to what has been reported in type 2 non-insulin-dependent diabetes, peripheral neuropathy may be the first chronic complication to become manifest. This observation provides additional evidence to suggest that each of the diabetic complications may have a different pathogenic mechanism.

Adult↗
PubMed1989

Insulin resistance and diabetes, mechanism and possible intervention.

The issue of the peripheral resistance to insulin action has been getting a lot of attention over the last decade. The reason for this is that insulin is a major regulatory hormone and is involved in the metabolism of carbohydrates, lipids, protein and ions. To understand the pathophysiology of insulin resistance it is necessary to elucidate the methods for the assessment of insulin resistance and the molecular mechanism of insulin action. Insulin action is impaired in pathologic and physiologic states such as diabetes mellitus and obesity as well as in some rare syndromes. Further understanding of the pathophysiology of the impaired action of insulin improves the chances of defining new ways of treatment to improve the sensitivity to insulin action.

Diabetes Mellitus↗
PubMed1988

Antecedent chronic hyperglycaemia blocks phlorizin-induced insulin resistance in the dog.

Hyperglycaemia may enhance insulin resistance typical of non-insulin dependent diabetes mellitus, as well as insulin dependent diabetes mellitus, and thus initiate a vicious pathogenetic cycle. We sought to test the hypothesis that reduction in chronic hyperglycaemia in the diabetic dog by methods that do not employ insulin may improve insulin resistance. We used the glucuretic agent phlorizin in dogs rendered chronically hyperglycaemic and diabetic by alloxan treatment. To analyse glucose disposition the euglycaemic clamp was performed. To minimize the role of counterregulatory influences that might be at play when glucose is reduced, the hyperglycaemic clamp with continuous somatostatin infusion was performed. Although phlorizin normalised plasma glucose in the diabetic dog and reduced plasma glucose in normal, non-diabetic dogs, insulin dependent glucose disposition rate did not improve. While phlorizin itself was associated with insulin resistance in the normal animals, the insulin resistance of diabetes mellitus was not further augmented. We conclude that phlorizin is associated with insulin resistance perhaps by a common pathway shared by chronic hyperglycaemia. Care must be taken when phlorizin is used as an agent to study glucose disposition.

Animals↗
PubMed1988

Relationship between lipoprotein levels and in vivo insulin action in normal young white men.

In epidemiologic studies, hyperinsulinemia has been found to be an independent risk factor for coronary heart disease (CHD). However, the mechanisms responsible for its role in atherogenesis remain unclear. We studied the relationship of in vivo insulin action and plasma lipids and lipoproteins in 44 normotriglyceridemic white men (aged 18 to 34 years). The euglycemic, hyperinsulinemic glucose clamp technique was used to quantitate insulin-mediated glucose disposal (M/I value) at a plasma insulin concentration of approximately 100 microU/mL. The M/I value correlated negatively with plasma triglycerides (r = -0.553, P less than .0001), as well as with fasting plasma insulin levels (r = -0.483, P less than .001), independent of age, body mass index, and fasting plasma glucose levels. A negative correlation of the M/I value was also observed with very low density lipoprotein (VLDL)-cholesterol (r = -0.347, P less than .05), VLDL-triglycerides (r = -0.474, P less than 0.005), and total cholesterol/high density lipoprotein (HDL)-cholesterol ratio (r = -0.431, P less than .01). The relationship between the M/I value and the total cholesterol/HDL-cholesterol ratio was independent of VLDL-cholesterol and VLDL-triglycerides, however, not independent of plasma triglycerides. No relationship was observed between insulin-mediated glucose uptake and total cholesterol, low density lipoprotein (LDL)-cholesterol, and HDL-cholesterol values. Individual differences in plasma triglycerides, fasting insulin concentration, and the total cholesterol/HDL-cholesterol ratio accounted for about half the variance observed in the M/I value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Severe diabetes induced in subtotally depancreatized dogs by sustained hyperglycemia.

Chronic clamping of plasma glucose levels at greater than or equal to 250 mg/dl in four partially depancreatized but previously nondiabetic dogs was followed within 2 wk by persistent hyperglycemia and glycosuria of less than or equal to 500 g/day, ketonuria, and weight loss. Three of the four dogs required daily insulin injections to control these catabolic manifestations. There was no evidence of spontaneous improvement of the severe diabetic state during the 39-69 days of observation after discontinuation of intravenous glucose infusion. Impairment of intravenous glucose tolerance, loss of the insulin response to glucose and arginine, fasting hyperglucagonemia, exaggerated glucagon responsiveness to arginine, and a significant reduction in sensitivity to insulin were characteristic of all diabetic dogs. Morphometric analysis of the endocrine pancreas revealed a profound reduction in the number and size of identifiable islets of the hyperglycemic dogs compared with islets from their own pancreases resected months earlier and with those from pancreatic remnants of eight subtotally depancreatized control dogs that had not been subjected to chronic hyperglycemic clamping. The reduction in number and size of islets of the hyperglycemic dogs was largely the consequence of depletion of insulin-containing cells and was similar to that of dogs with long-standing alloxan-induced diabetes. In the eight control dogs, clinical evidence of diabetes did not develop during a follow-up period of 193-296 days. In this group, there was no evidence of diminution of intravenous glucose tolerance, of the insulin response to glucose or arginine, or of insulin sensitivity as determined by an acute hyperinsulinemic hyperglycemic clamp. The number and size of islets and number of beta-cells in pancreatic remnants from these dogs did not differ morphometrically from those of the pancreatic segment that had been resected. We conclude that in subtotally depancreatized but nondiabetic dogs, maintenance of constant hyperglycemia of greater than or equal to 250 mg/dl by means of intravenous glucose infusion causes a severe, persistent, and often insulin-requiring diabetic state that does not occur in the absence of the hyperglycemia.

Animals↗
PubMed1984

[Tumors of the glomus caroticum].

From 1952 to 1982 15 patients (6 male, 9 female) with 20 carotid body tumors have been treated in the surgical departments of the universities of Berlin and Heidelberg. A recurrent tumor occurred in 3 patients, in one case appeared a further recurrence. Two patients presented with a tumor of the glomus jugulare as well as the tumors of the carotid body and with a familial accumulation. While still in the 60's the surgical procedure was in doubt due to high complications and lethality rates today, because of the progress in carotid surgery with the insertion of an intraluminal shunt, the operation is recommended without risk. An important part plays a certain preoperative diagnosis through the B-mode sonography for the operative strategy.

Adult↗