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P Berchtold

Publications and source records attributed to P Berchtold.

At least 37 records · Page 2Linked to original sources

Autoantibodies in chronic ITP.

Chronic ITP is a syndrome of destructive thrombocytopenia due in most cases to antiplatelet autoantibodies. In the present studies we have studied 74 patients with chronic ITP using a new immunobead assay. Of these, 59 (79.7%) had demonstrable platelet-associated autoantibodies: 48 against platelet glycoprotein IIb/IIIa and 11 against glycoprotein Ib/IX. Plasma autoantibodies were studied in all patients and 32 (43.2%) had positive results; in each case the patient also had platelet-associated autoantibodies directed to the same antigen. We conclude that the majority of patients with chronic ITP have autoantibodies against platelet membrane glycoproteins and that the immunobead assay is a sensitive and reproducible method for their detection which is applicable to the routine hospital laboratory.

Autoantibodies↗

Autoantibodies to platelet glycoproteins in patients with disease-related immune thrombocytopenia.

Although increased platelet destruction and elevated platelet-associated IgG have been shown in patients with lymphomas and various autoimmune diseases, such as systemic lupus erythematosus (SLE), there have been few studies evaluating autoantibodies against platelet-specific antigens. We evaluated 24 patients retrospectively with disease-related thrombocytopenia (12 with lymphoproliferative diseases and 12 with various autoimmune disorders) using a recently reported antigen-specific assay. Autoantibodies against platelet GPIIb/IIIa or GPIb/IX were noted in 15 of the 24 patients (10 of 12 with autoimmune disease and five of 12 with lymphoproliferative disorders). Platelet-associated autoantibodies were present in 60% and plasma autoantibodies in 33%. Anti-GPIIb/IIIa autoantibodies were much more common than those against GPIb/IX. In one patient each with thrombocytopenia and either SLE or myasthenia gravis, absorption of plasma with platelets completely removed the anti-GPIIb/IIIa autoantibodies, but did not affect the level of anti-cochlear autoantibody involved with immune-mediated hearing loss in the SLE patient or the anti-acetylcholine receptor autoantibody in the myasthenic patient. These findings show that, in some cases of disease-related immune thrombocytopenia, autoantibodies against GPIIb/IIIa or GPIb/IX can be detected similar to those seen in chronic ITP. As shown in two patients with multiple autoimmune manifestations, the various autoantibodies have diverse specificities and do not crossreact.

Adolescent↗

Autoantibodies against platelet membrane glycoproteins in children with acute and chronic immune thrombocytopenic purpura.

The autoimmune nature of chronic immune thrombocytopenic purpura (ITP) in adults is widely accepted. In contrast, the pathogenetic mechanism in acute and chronic ITP in children is not known. In this report, we studied 39 children with destructive thrombocytopenia, 15 patients with acute ITP and 24 patients with chronic ITP. Platelet autoantibodies to platelet glycoprotein IIb/IIIa were detected in 14 of 24 patients (58.3%) in the chronic ITP group and in four of 15 (26.7%) with acute ITP. Binding ratios (+/- SD) of positive patients were significantly greater (P = .01) in chronic ITP (8.0 +/- 9.1) when compared with those of acute ITP where the binding ratios were only slightly above the normal range (1.9 +/- 0.4). The results show that autoantibodies against platelet glycoproteins are present in the majority of children with chronic ITP confirming the autoimmune nature of this disorder. The minimal elevation seen in the positive children with acute ITP suggests a different pathogenetic mechanism. These data suggest that this approach may be useful in differentiating acute from chronic ITP patients.

Acute Disease↗

Platelet-associated and plasma anti-glycoprotein autoantibodies in chronic ITP.

Chronic immune thrombocytopenic purpura (ITP) is due to platelet destruction by circulating antiplatelet antibody. Although autoantibodies against the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) complex and GPIb have been demonstrated using various methods, practical assays for detection of platelet-associated or plasma autoantibodies have not been available. We studied 59 patients with chronic immune thrombocytopenic purpura in whom platelet-associated and plasma autoantibodies against the GPIIb/IIIa complex and GPIb were measured using a newly developed immunobead assay and a previously reported microtiter-well assay. Platelet-associated autoantibody was detected using the immunobead assay in 21 of 28 patients (75.0%; 13 with anti-GPIIb/IIIa, 8 with anti-GPIb). Plasma autoantibodies were noted in 34 of 59 patients (57.6%; 21 with anti-GPIIb/IIIa, 11 with anti-GPIb, and 2 with both). Positive results were noted in 30 of 59 patients using the immunobead assay and in only 14 of 59 using the microtiter-well assay, suggesting that solubilization of the platelets prior to antibody addition, as in the microtiter-well assay, alters epitope stability. Of the 31 thrombocytopenic control patients studied, all gave negative results using both assays. We conclude that these clinically adaptable assays allow detection of autoantibodies in most patients with chronic ITP, confirming the presence of an autoimmune process.

Autoantibodies↗

In vitro tests overestimate in vivo neutralizing capacity of antacids in presence of food.

The neutralizing capacity of two antacids (Alucol = A, Syntrogel = S), differing both in their composition and theoretical neutralizing capacity, was evaluated in vitro and in vivo. In vitro at pH 3.5, 1 ml of A or S neutralizes 3.9 and 1.6 meq of acid, respectively, in an aqueous solution. When tested in vivo in the absence of food during near maximal acid secretion, induced by impromidine, 60 ml of either A or S reduced the 4-hr mean H+ activity by 83% and 65%, respectively. In contrast, the reduction of the 12-hr H+ activity observed after repeated administration of 30-60 ml of A or S at the end of the postprandial hour failed to reach significance with both preparations. This suggests that interaction with food produces a considerable loss of in vivo antacid neutralizing capacity, not quantitatively predictable from in vitro tests.

Adult↗

[Diagnostic problems in acute pulmonary embolism].

In a retrospective study over the years 1978-1982, 729 cases of acute pulmonary embolism were analyzed in relation to history, clinical signs and laboratory findings and the results compared with the findings of the urokinase pulmonary embolism trial. As far as history and clinical symptoms were concerned, breathlessness, chest pain, tachypnea, tachycardia and cyanosis were the dominating features. Among laboratory tests, the radiological and electrocardiographic findings of pulmonary hypertension were of little value. In contrast, arterial hypoxemia and isotope scanning provided the most reliable diagnostic information. The most frequent problem in differential diagnosis was acute myocardial infarction.

Acute Disease↗

[Immune complexes in the serum of patients with acute myeloblastic leukemia].

This study was performed to determine whether the nature of the hemolytic factor present in 54% of sera collected from patients during the active stage of acute myeloid leukemia (AML) [1] is immune complex (IC)-like. The fluid phase C1q-binding test (C1q-BT) served to analyze 92 sera from 24 patients with AML. In a first study the C1q-BT as modified by Carpentier [2] was compared to the universally accepted C1q-BT as described by Zubler [3]. Binding of C1q to heat aggregated human IgG, to tetanus toxoid (Te)/anti-Te complexes, and to serum containing heparin or fibrinogen was to a similar extent concentration-dependent; however, the binding values obtained with the method of Carpentier were always higher than with the method of Zubler. The same was found for the binding of C1q to sera from patients suffering from various diseases: using Carpentier's method approximately a 20% higher C1q-binding activity was found for all samples compared to binding activities found with Zubler's original method. The higher C1q binding did not depend on higher sensitivity of Carpentier's assay system, as the binding to sera from 60 healthy individuals was also elevated (8.1 +/- 6.0% vs 1.2 +/- 1.0% with the method of ZUBLER). In a second study AML sera were analyzed by the "extended" C1q-BT [4]. The "extended" C1q-BT uses two different C1q preparations and the assay follows the procedure described by ZUBLER. This test is able to detect immune-aggregate-mediated and non-immune-aggregate-mediated C1q binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Antibody Complex↗

The effects of an alpha-glucoside hydrolase inhibitor on glycemia and the absorption of sucrose in man determined using a tracer method.

Acarbose, an alpha-glucosidase inhibitor, lowers the glycemic excursion following the ingestion of carbohydrates, in particular, sucrose. This was confirmed with increasing doses of acarbose (0, 50, and 100 mg) and the causes investigated. The absorption of the glucose moiety of sucrose was determined from plasma tracer concentrations when overnight-fasted normal subjects received a 100-g oral sucrose load labeled with sucrose [(1-14C]glucose and a simultaneous intravenous infusion of [3-3H]glucose. As the dose of acarbose given with the sucrose load was increased from 0 to 100 mg, the percentage of the load appearing in the peripheral circulation decreased from 90% to 62%. Malabsorption was confirmed by the appearance of breath hydrogen. Simultaneously, absorption time increased from 243 to 411 min. Maximal glycemic excursions were therefore lowered from 64 to 31 mg/dl. The plasma concentrations of gastric inhibitory polypeptide and insulin decreased with the acarbose dose so that the fractional disappearance rate of glucose also decreased. However, the concentrations of glucagon-like immunoreactivity (GLI) rose, confirming the ileal appearance of malabsorbed sucrose.

Acarbose↗

Long-term treatment in diabetics with acarbose, a glucosidase inhibitor: efficacy, tolerability and effect on GI hormones.

12 months therapy with acarbose in 143 type I and type II patients markedly improved the metabolic control, assessed by fasting and postprandial blood glucose determination. During 5 year acarbose treatment GIP levels were decreased and enteroglucagon levels were elevated. After withdrawal of the drug for one week GIP levels increased and enteroglucagon concentrations fell. Thus, GI-hormone changes were reversible after discontinuation of acarbose. Tolerability of acarbose was good and clinical chemistry and haematology parameters showed no changes after 1-5 years acarbose therapy. Approximately 60% of the patients had intestinal symptoms which subsided again for most patients after 1-4 weeks therapy with acarbose. Body weight remained unchanged. The glucosidase inhibitor acarbose is a new effective and safe therapeutic concept in the treatment of diabetes mellitus.

Acarbose↗

Functional and morphologic characterization of human insulinomas.

Circulating levels of insulin, proinsulin-like component, glucagon, growth hormone, and pancreatic polypeptide were measured in 12 patients with functioning insulinomas, and the suppressibility of serum insulin by somatostatin and diazoxide was assessed before surgical removal of the tumors. The hormone content of the tumors was evaluated by radioimmunoassay and by immunofluorescence and the structure of the tumor cells by electron microscopy. Based on these findings, we propose a new classification of insulinomas in two groups: group A is characterized morphologically by abundant well-granulated typical B-cells, trabecular arrangement of tumor cells, and uniform insulin immunofluorescence; functionally, these tumors are associated with a moderate elevation of proinsulin-like component and with an almost complete suppressibility of serum insulin by somatostatin and diazoxide. In contrast, tumors of group B are characterized by scarce well-granulated typical B-cells, a medullary-type histologic structure, and irregular insulin immunofluorescence; functionally these tumors show elevated circulating levels of proinsulin-like component and a marked resistance of insulin secretion to somatostatin and diazoxide inhibition. This way of separating human insulinomas in groups A and B represents a simplification of existing classifications and emphasizes the quantitative ultrastructure in relationship to suppressibility of insulin secretion. The proposed classification of human insulinomas in groups A and B, however, does not allow the assessment of the clinical or histopathologic malignancy of the tumors.

Adenoma, Islet Cell↗

Blood glucose concentrations and glycosuria during and after one year of acarbose therapy.

Type-I and type-II diabetics receiving antidiabetic therapy, comprising of diet, or diet plus sulphonylureas or insulin, were additionally treated with acarbose for a period of 12 months in an open, multi-centre study carried out under general practice conditions. This was followed by an observation period without acarbose. After 3 months on acarbose, the mean fasting and post-prandial blood glucose concentrations were 30 and 40 mg/dl, respectively, lower, thereafter remaining virtually unchanged up to the end of treatment. After withdrawal of acarbose the mean blood glucose values rose to their pretreatment levels, except in patients with proven poor acarbose compliance. All three treatment subgroups mentioned above showed the same pattern of glucose reduction. The mean blood glucose values of patients previously treated by dietary measures alone fell under acarbose therapy below the upper limit of normal. The percentage of glycosuric patients in the above subgroups was halved under acarbose and rose after discontinuation of acarbose approximately to the initial numbers. The number of patients with blood-glucose control classified as "good" rose fourfold during the acarbose treatment. In the course of the trial acarbose had to be discontinued due to intestinal side effects in only 5% of the patients. Frequency and intensity of the intestinal symptoms related to increased bacterial carbohydrate cleavage (flatulence, meteorism, occasionally diarrhoea), decreased during treatment. Other subjective complaints or side effects were neither reported nor could be detected objectively.

Acarbose↗

Obesity and hypertension: epidemiology, mechanisms, treatment.

There is a close epidemiological association between obesity and elevated blood pressure for all age groups, although not every obese individual becomes hypertensive. In populations without age-related increases in body weight, an elevation of blood pressure with age is not seen. Mechanisms included in the development of hypertension in obesity are hyperinsulinemia, insulin induced sodium retention and increased sympathetic tone. Overnutrition with over intake of sodium and lack of physical exercise contribute to the metabolic syndrome of obesity. Thus, weight reduction by decreased energy uptake and increased physical exercise is recommended in the treatment of hypertension in obese patients. The resulting fall in insulin levels may lead to decreased sodium absorption in the kidney. Although treatment of obesity by weight loss decreases blood pressure substantially, a minority of patients do not respond to the weight loss. Blood pressure generally decreases before normal weight is achieved. Salt intake reduction does not appear to explain why weight reduction lowers blood pressure. Reduced levels of plasma renin activity, serum aldosterone levels, catecholamine levels and serum insulin levels may be involved in the blood pressure lowering associated with weight loss. Since the risk of cardiovascular disease in the hypertensive patient is not only determined by the blood pressure, an overall treatment which aims at reduction of other risk factors such as glucose intolerance and hyperlipoproteinemia is advocated. Thus, in any obese hypertensive patient normalization of excess body weight and increased physical activity appears to be the first and most important step of any rational therapeutic strategy.

Adolescent↗

[Continuous subcutaneous insulin infusion brings about normal blood sugar in type I diabetes mellitus despite relaxing of diet instructions].

In 6 normal weight juvenile diabetic patients treated with continuous subcutaneous insulin infusion (CSII) we have investigated whether the restrictive management of the diabetes diet could be relaxed. On 2-3 days of a 4 week period the patients ate a) a conventional diabetes diet consisting of 3 main meals and in-between snacks of a prescribed carbohydrate content or b) a liberal diabetes diet in which the patients could choose the number of meals and carbohydrate contents. With both diets, mean blood glucose levels during the day were in normal range (96 +/- 3 and 101 +/- mg/dl, mean +/- SEM). On the liberal diet meal frequency and carbohydrate intake per day were significantly lower, the carbohydrate content per meal significantly larger when compared with the conventional diabetes diet. There was not difference in insulin requirements per day (basal rate plus premeal dosage). All the patients preferred the liberal diet. CSII allowed juvenile diabetic patients a more liberal management of their diabetes diet without negative effects on blood glucose control. Hence CSII improved the quality of life in these patients.

Adult↗

Treadmill training improves intravenous glucose tolerance and insulin sensitivity in fatty Zucker rats.

The effect of treadmill training on intravenous glucose tolerance and insulin sensitivity was investigated in Zucker rats (fafa). In 25-week-old fafa animals with the typical metabolic syndrome of massive obesity, glucose intolerance, hypertriglyceridaemia and insulin resistance, treadmill exercise of only very mild intensity was carried out for 6 weeks. The training programme induced a marked reduction in basal and post-glucose challenge plasma insulin levels and a slight but significant improvement of intravenous glucose tolerance. No alteration in insulin sensitivity of the isolated perfused hindquarter was demonstrable. In another study a 9-week training programme was started in 7-week-old fafa rats before the development of their metabolic syndrome. In the sedentary control animals glucose intolerance and insulin resistance developed during the study period; in the training group, both the deterioration of glucose tolerance and the decrease of insulin sensitivity were prevented. This study demonstrates in fafa rats that (a) in young animals physical training may prevent a genetically predisposed deterioration of glucose tolerance and insulin sensitivity and (b) in adult animals mild physical training may improve intravenous glucose tolerance and insulin sensitivity.

Animals↗

Obesity-associated disorders in normal-weight individuals: some speculations.

A number of disorders including maturity-onset (Type II) diabetes, hypertension and hypertriglyceridemia are frequently associated with adult-onset obesity and improve with energy restriction. It is the premise of this brief review that there are patients with these disorders who are not obese according to standard criteria; but who would also respond favorably to energy restriction. It is proposed that these 'metabolically-obese, normal weight' individuals might be characterized by hyperinsulinism and possibly an increase in fat cell size, compared to patients of similar age, height and weight and/or to themselves at an earlier time. It is also proposed that in some of these individuals inactivity and diet composition might be important contributing factors, and that for them, the appropriate therapy would include exercise and altered diet composition.

Adult↗