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Biomedical subjects

K M Goebel

Publications and source records attributed to K M Goebel.

At least 55 records · Page 3Linked to original sources
PubMed1977

Levamisole-induced immunostimulation in spondylarthropathies.

The term "seronegative spondylarthritis" (S.S.A.) has been assigned to rheumatic disorders with closely related clinical features, defined by seronegativity and HLA-B27 phenotype. Its pathogenesis may be linked with a genetically controlled defective immune response. Therefore, 37 men with S.S.A. were treated with levamisole (150 mg/day, 3 days/wk) to stimulate the immune reactions. In a randomised controlled crossover study these patients also received a placebo; each period ran for 12 wk. Symptomatic therapy was continued through the entire 6 mo. Serious side-effects led to withdrawal of the active drug in 9 patients. Clinical response was measured in terms of a cumulative joint index, spondylometry, morning stiffness, and a pain scale. Treatment with levamisole resulted in a significant improvement in these parameters. Radiological evidence of sacroiliitis was present in 48.6% before and after levamisole, and joint scanning with 99Tc-pyrophosphate also revealed no progress in the disease. After levamisole treatment, IgM levels fell significantly (P less than 0-014). Likewise, the previously high percentage of antibodies with weak cytotoxic activity against lymphocytes was reduced after levamisole (P less than 0-049), and an increased rate of leucocyte-migration inhibition (L.M.I) was found in the levamisole-treated group. Thus, the immunostimulating properties of levamisole may interfere with defective immunoregulation in S.S.A. and, by improving the clinical conditions, lead to a change in the course of this disease.

Adult↗
PubMed1977

Red cell metabolic and membrane features in haemolytic anaemia of alcoholic liver disease (Zieve's syndrome).

Zieve's syndrome (ZS), which consists of transient haemolytic anaemia, jaundice, hyperlipoproteinaemia, and alcohol-induced liver disease, was studied in male patients during the acute (n = 20) and the remittent (n = 10) phase. Chronic alcoholics (n = 10) without haemolysis and healthy male persons (n = 10) served as controls. Erythrocytes were separated into old and young cells by means of density-layer centrifugation. Those fractions which contained older red cells disclosed a pyruvate-kinase instability which resulted in impaired metabolism. Changes in membrane lipid composition as indicated by increased cholesterol and polyunsaturated fatty acids (PUFA) were also detected in patients during the acute phase of ZS. Alcohol-induced red-cell vitamin-E deficiency with a decrease in PUFA levels may provoke an oxidation of reduced red-cell glutathione which in turn results in the enzyme instability. This study lends further support to the hypothesis that the putative role of the red-cell metabolic injury in the origin of haemolysis in ZS cannot be envisaged without introducing membrane-linked and extracellular cofactors.

Adult↗
PubMed1976

[Effect of an oral contraceptive (ethinylestradiol/D-norgestrel) on growth hormone and insulin secretion].

The growth hormone, insulin and blood glucose values were measured during a glucose tolerance test in 12 women before and after 3 months' use of a contraceptive of the sequential type (11 pills containing 0.05 mg D-norgestrel and 0.05 mg ethinylestradiol and 10 pills containing 0.125 mg D-norgestrel and 0.05 mg ethinylestradiol). Neither fasting blood glucose nor glucose tolerance are altered during administration of the contraceptive steroids. On the other hand, the reactive insulin level is significantly increased in comparison to the basal value, thus showing the signs of hyperinsulinemia. Both the gestagens and the estrogens appear to contribute to this disturbance of insulin secretion. Presumably the hyperinsulinemia is an expression of decreased sensitivity of the peripheral tissue to insulin. The growth hormone, a so-called insulin antagonist, is not responsible for the "insulin resistance" observed. The values measured by us after administration of the contraceptive do not significantly differ from the basal values.

Adult↗
PubMed1976

[Lymphocyte antigens in autoimmune thrombocytopenia].

18 patients with proven autoimmune thrombocytopenic purpura (ATP) (group A) were screened for human lymphocyte antigens (HLA) and compared with 13 patients with secondary thrombocytopenic purpura (group B). An additional comparison was made with a control panel of a European population (group C). HLA-B8 was present in 12 of 18 patients (66.6%) of group A, compared with only one of 13 patients (7.6%) of group B. HLA-B12 occured in 8 of 18 patients (44.4%) of group A, compared with, again, only one of 13 patients in group B. The alleles HLA-B8/B12 were observed in 7 of 18 patients (38.8%) of group A, whereas no patient of group B exhibited such phenotypes. The differences were statistically significant (p less than 0.001 to p less than 0.03). A high incidence of the antigens HLA-B8/B12 has been noted in a family of which three members displayed serious symptoms of ATP over three generations. Thus, it is conceivable that individuals who carry the HLA-B8/B12 alleles run an increased risk of developing the disease if they are exposed to additional causal factors which finally trigger ATP.

Adolescent↗
PubMed1976

[Changes of erythrocyte membrane lipids in ethanol induced hyperlipidemia (Zieve's syndrome) (author's transl)].

In 11 patients with alcohol-induced hyperlipemia, of whom 6 showed a Zieve Syndrome increased phospholipids, triglycerides and total cholesterol were found in the red cells stromal. The gasliquid chromatographic analysis of the phospholipid fatty acids showed increased contents of saturated and monounsaturated fatty acids C 16-C 18 smaller contents of longchain highly unsaturated fatty acids. The changes in the fatty acid pattern mainly occurred in patients with Zieve Syndrome and could be important for the mechanism of the hemolytic anemia. Theses findings could be in connexion with vitamin E deficiency.

Adult↗
PubMed1975

[Adaptive metabolic disorders in erythrocytes during shock].

In patients with shock the metabolic activity of the red blood cells was studied following separation according to cell-age by density layer centrifugation using Stractan II-Urografin solutions. Metabolic acidosis in patients with cardiogenic shock (n = 8) and with postoperative shock (n = 7) induced a pronounced fall in 2,3-diphosphoglycerate (2,3-DPG) levels and in adenosine triphosphate (ATP), in contrast to a raised lactate-pyruvate ratio. 2,3-DPG values were higher than normal in patients with hypoglycemic shock (n = 12), whereas further measured substrate levels were markedly decreased. The levels of these compounds of the red blood cells revealed a significant difference in the hemolysates derived from cells separated according to cell-age. The shock syndrome was also observed in patients suffering from severe congestive heart failure (n = 10) who received dopamine (300 mug/min) for its known action in improving hemodynamics and renal function. Following drug administration for 150 min a clinical improvement was associated with a change of extent and pattern of the red blood cell metabolic disorder.

Acidosis↗
PubMed1975

[Insulin and proinsulin secretion under contraceptive steroid administration (author's transl)].

An ivestigation has been performed in 49 women about the influence exerted on the glucose-tolerance, insulin and proinsulin secretion by hormonal contraceptives of different types and compositions. A disturbed dynamics of the insulin secretion with elevated values in the OGTT at two and three hours has been proven at a nearly equal degree using combined preparations (Anacyclin, Eugynon, Neogynon, Mikrogynon) or sequential preparations (Kombiquens, Ovanon). Though there has been interference with the glucose tolerance, the serum proinsulin in the OGTT showed increased levels too. When a combined preparation was applied, the proinsulin values were significantyl higher compared to a sequential type contraceptive. The observed disturbance of the insulin and proinsulin secretion is explained by a decreased sensitivity to insulin in the peripheral fat tissue. The actual dose of the estrogen-gestagen components has no influence on the described changes. Elevated insulin levels are demonstrable already during the first treatment cycle. The degree of the disturbance is independent of the duration of the medicamentous application during the first 6 contraceptive months. After withdrawal of the respective contraceptive steroid the insulin secretion showed nearly normal dynamics during the subseqeunt menstrual cycle.

Blood Glucose↗
PubMed1975

Red cell metabolism in transient haemolytic anaemia associated with Zieve's syndrome.

Reversible haemolytic anaemia associated with decreased red cell half-life and reticulocytosis was studied in 10 patients with Zieve's syndrome. Since the underlying cause of the red cell destruction is as yet unknown, we determined the critical metabolic functions of the red cells in order to define the assumed intracorpuscular defect causing haemolysis. The glucose metabolizing enzymes had normal or raised values. - In view of the diminished ATP and raised 2,3-diphosphoglycerate (2.3 DPG) levels - a combination which suggests a pyruvate kinase (PK) deficiency - additional procedures were carried out in order to detect an abnormal activity of the red cell PK. Studies of biochemical properties of PK such as thermostability, Michaelis-Menten constants, and activation and inhibition tests brought results markedly deviating from the norm.-Fractions containing old cells particularly disclosed PK instability. A defective red cell matabolism resulted which was measurable through ATP-instability, altered glucose utilization and lactate production. - Experimental cell aging procedures led to a markedly decreased red cell metabolism. These assays revealed that mutations of PK-control mechanisms might be involved as factor triggering haemolytic anaemia of Zieve's syndrome.

Adult↗
PubMed1975

Haemolytic anaemia with hereditary pyruvate kinase instability developing acute leukaemia.

The case of a 27-year-old woman with pancytopenia, revealing acute monocytic leukaemia and haemolytic anaemia, is described in detail. The underlying cause for the red cell destruction was found to be a pyruvate kinase (PK) instability. Further investigation into three generations of her family (n = 12) disclosed a hereditary PK instability. This was proven by performing biochemical studies to elucidate mutants representing a structurally defective enzyme. Since conversions of pancytopenia with acquired red cell enzyme deficiency into leukaemia have been described, our observation emphasizes that hereditary red cell enzymopathy might also be associated with adult acute leukaemia.

Adenosine Triphosphate↗
PubMed1975

Adaptation of red cell enzymes and intermediates in metabolic disorders.

The metabolic activity of the red cell glycolytic pathway hexose monophosphate shunt (HMP) with dependent glutathione system was studied in patients with hyperthyroidism (n = 10), hyperlipoproteinemia (n = 16), hypoglycemia (n = 25) and hyperglycemia (n = 23). In uncontrolled diabetics and patients with hyperthyroidism the mean value of glucose phosphate isomerase (GPI), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR) was increased, whereas these enzyme activities were reduced in patients with hypoglycemia. Apart from a few values of hexokinase (HK) which were lower than normal the results in hyperlipoproteinemia patients remained essentially unchanged, including the intermediates such as 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP) and reduced glutathione (GSH). While increased rates of 2,3-DPG and ATP in hypoglycemia patients were obtained, these substrates were markedly reduced in diabetics.

Diabetes Mellitus↗