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Biomedical subjects

U Becker

Publications and source records attributed to U Becker.

At least 19 recordsLinked to original sources

Insulin-like growth factor 1 and growth hormone in chronic liver disease.

Somatomedins or insulin-like growth factors (IGF) are peptides synthesized in the liver. IGFs have different anabolic and metabolic actions and are important in normal growth and development. The concentration of insulin-like growth factor 1 (IGF-1) is low in patients with chronic liver disease mainly due to the decreased liver function. Low levels of somatomedins are also seen in patients with growth hormone (GH) insufficiency, renal impairment, and malnutrition. GH stimulates the production of IGF-1, and both are part of a negative feedback system acting on hepatic, pituitary, and hypothalamic levels. The basal and stimulated GH concentration is pathologically elevated in patients with chronic liver disease and may be due to a disturbed regulation. Alterations in liver IGF receptors in patients with chronic liver disease still require investigation as they may be important for the liver function.

Chronic Disease

Variation in hepatic estrogen receptor concentrations in patients with liver disease. A multivariate analysis.

Hepatic estrogen receptor concentrations were measured in liver biopsy specimens from 102 patients (58 women and 44 men) with liver disease and correlated to several clinical, biochemical, and histologic background variables by means of multiple regression analysis. Half of the tissue was processed for histologic evaluation with a semiquantitative registration of histologic characteristics, whereas the other part was used for receptor analysis by enzyme immunoassay. Fifteen patients with no or minimal histologic changes served as controls. The analysis shows that the reduced estrogen receptor concentrations observed in patients with chronic liver diseases reflect the degree of liver dysfunction and not the specific type of liver disease. Serum albumin, log serum bilirubin, log serum alkaline phosphatases, and the degree of parenchymal fibrosis were significantly related to hepatic estrogen receptor level in the final regression model, but only part of the variation can be explained by these variables, and other factors must be of importance.

Adult

Micronucleus assay prediction and application optimized by cytochalasin B-induced binucleated tumor cells.

Improvement in the predictive assertion of the micronucleus assay was achieved by treating human malignant melanoma cells (Mewo) with cytochalasin B (CB), generating binucleated cells (BNC) representing cells after a single karyokinesis. Optimal cell binucleation was determined by testing several cytochalasin B concentrations and different incubation times. On average, 56% binucleated cells were found after incubation with 2 to 3 micrograms/ml cytochalasin B for 48 h. Cells with at least one micronucleus (Mn) were defined as fraction of cells with micronuclei and describes the degree of damaged cells. We found in binucleated cells 2.2 fold the fraction of cells with micronuclei than in mononucleated cells (MNC), as expected assuming that an induced micronucleus is associated with only one single daughter cell after mitosis. The mean of micronuclei per binucleated cells, however, was enhanced about 2.9 fold in relation to that of micronuclei per mononucleated cells and is related to the nuclear damage per cell. The application of cytochalasin B did not enhance the fraction of damaged cells although the degree of the injury per cell is intensified. A micronuclei promoting or inhibiting effect of the experimental design due to changes in cell proliferation was excluded by cytofluorometric investigations of DNA content and synthesis after cytochalasin B application. A comparison of the modified with the conventional micronucleus assay shows the superiority of the former.

Cell Line

Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease.

In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were significantly (p less than 0.05) younger at the time of natural menopause than controls. Compared to controls, non-cirrhotic alcoholic women had significantly (p less than 0.05) reduced levels of DHAS, significantly (p less than 0.05) more alcoholic cirrhotic women had detectable oestradiol concentrations, elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione and dehydroepiandrosterone sulphate (DHAS) (p less than 0.05). The observed changes may be a consequence of liver disease since similar changes were observed in patients with alcoholic and non-alcoholic liver disease, but an additional effect of alcohol cannot be excluded.

Aged

Enzyme immunoassay of oestrogen receptors in needle biopsies from human liver.

For quantitative assessments of sex hormone receptors in liver tissue, ligand binding assays are inconvenient, as they require large biopsies (0.5-1.0 g). The present study shows that it is possible to measure oestrogen receptors (ER) quantitatively in needle biopsy specimens as small as 10 mg by modifications of a commercial enzyme immunoassay employing monoclonal antibodies. Sucrose gradient centrifugation and the dextran charcoal method served as reference methods. A consecutive series of needle biopsies from patients suspected of liver disease were investigated. The biopsies (n = 37) had a median weight of 14 mg and cytosolic protein concentrations greater than 1 mg/ml (median 1.28 mg/ml). The median ER concentration was 20 fmol/mg cytosolic protein (range 5 to 57 fmol/mg). The intra-assay coefficient of variation was 8.9%, the inter-assay 13.2%, and the detection limit 2.7 fmol/ml cytosol. Women had significantly higher ER concentrations (median 22 fmol/mg) compared to male patients (median 16 fmol/mg) (P = 0.007). The enzyme immunoassay measures ER in liver specimens as small as 10 mg, compared to the large tissue specimens necessary for the conventional DCC assay, and the method is a convenient tool for further studies of ER in routine needle biopsies from the liver.

Biopsy, Needle

Sex hormones in postmenopausal women with primary biliary cirrhosis.

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction.

Aged

[Goals and methods of health training in the rehabilitation hospital for cardiovascular diseases].

Presented are the objectives, premises, and methods of health training in the framework of inpatient rehabilitation of cardiovascular patients, the contents of a two-week group programme are reported. Central among the goals is information on the disease, on how to cope with it, as well as psychosocial reorientation of health behaviour. Various methods for achieving these goals are described, the focus being on group work programmed according to psychological considerations, and placed within a psychosomatic overall approach of the clinic.

Adaptation, Psychological

Oral premedication in children. A comparison of trimeprazine with a trimeprazine, droperidol and methadone mixture.

One hundred children who presented for minor general surgical procedures were randomly assigned to receive one of two oral premedications. Those in group A (n = 50) were given 3 mg/kg of trimeprazine and those in group B (n = 50) a mixture of trimeprazine 1.0 mg/kg, droperidol 0.15 mg/kg and methadone 0.08 mg/kg. Patients in group B were more likely to be asleep on arrival in the anaesthetic room (p less than 0.02) and were less likely to be distressed at induction of anaesthesia (p less than 0.02). Thiopentone requirements were less in group B (p less than 0.001). The incidence of side effects was similar in the two groups. It is concluded that the mixture produces more satisfactory sedation than trimeprazine.

Administration, Oral

Radiolysis of DNA in aqueous solution in the presence of a scavenger: a kinetic model based on a nonhomogeneous reaction of OH radicals with DNA molecules of spherical or cylindrical shape.

Two expressions are given for the survival dose of DNA exposed to high-energy radiation in aqueous solution in the presence of a scavenger. They are derived from a model where a diffusion controlled reaction of OH radicals occurs on the surface of the DNA macromolecules in competition with scavenging in the bulk of the solution. The DNA molecules are approximated either by spheres or by cylinders. The model based on molecules of spherical shape corresponds closely to that developed by van Rijn et al. [20]. Expressions obtained from the cylindrical model are used to account for the dependence on the scavenger concentration of some experimentally measured quantities, namely the survival dose and the G value for single-strand breaks upon Co gamma-irradiation of phi X174 DNA and polyadenylic acid, respectively.

DNA

Menstrual disturbances and fertility in chronic alcoholic women.

Data on menstrual pattern, gynecological disorders and infertility were obtained from 51 chronic alcoholic women aged 20--42 years attending an outpatient clinic for alcoholics, using 51 randomly drawn age-matched healthy women as controls. A higher variability (P less than 0.05) in the duration of both menstrual cycle and menstrual flow was recorded in the chronic alcoholic women during active alcoholism. A higher frequency (P less than 0.05) of menstrual disturbances (70% vs. 55%) and uterine curettages (38% vs. 16%) were found in the alcoholic women. The latter reported more abortions (63% vs. 28%, P less than 0.001) and miscarriages (23% vs. 8%, P less than 0.05) than controls, but due to a higher number of pregnancies in the alcoholic group the proportion of abortions and miscarriages did not differ significantly. No differences existed between the groups regarding frequency of difficult conception. Social classification had no independent influence on the results. The study shows that chronic alcoholic women are more prone to menstrual abnormalities and are at greater risk of gynecological interventions, while they do not seem to have reduced fertility.

Adolescent

The effect of astemizole on bronchial hyperresponsiveness and exercise-induced asthma in children.

The ability of the new generation H1-receptor antagonist, astemizole, to prevent histamine-induced airway obstruction and exercise-induced asthma (EIA) was studied in 20 children with asthma. The study was a randomised clinically controlled trial of oral astemizole versus placebo in a cross-over study. In each of the two treatment periods the children were tested at days 0, 6, 15 and 22 of therapy. The two treatment periods were separated by a washout period of 50 days, and at each visit a bronchial challenge with increasing concentrations of histamine followed by an exercise test was performed, and peak flow and asthmatic symptom score were recorded daily. The children tolerated significantly higher mean concentrations of histamine when treated with astemizole compared with placebo (P less than 0.001). Astemizole postponed the response to exercise, but no change in the maximal response was found. No differences between the treatment periods were found regarding frequency of asthmatic symptoms or the daily recording of peak flow.

Administration, Oral

Determination of plasminogen activator inhibitor (PAI) capacity of human plasma in presence of oxidants: a novel principle.

A new functional assay of PAI-activity in human plasma is described. Hitherto known assays for fast acting PAI have some disadvantages: predilution and/or acidification steps of the sample to afford the required inactivation of alpha-2-antiplasmin (A2-PI). This approach in contrast implicates test performance in presence of chloramine T (CT), an oxidant that destroys plasma antiplasmin activity without impairing significantly the activity of urokinase (u-PA) or plasmin. The following reaction conditions were found optimal: 50 microliter of undiluted plasma, anticoagulated with citrate or EDTA, were first incubated with 1 IU u-PA in a Tris-buffer, pH 8.4 and then with Glu-plasminogen (0.85 mumol/l final), CT (2.5 mmol/l final), tranexamic acid (0.9 mmol/l final) for 5 min. at 37 degrees C. After addition of 0.3 mmol/l of the chromogenic plasmin substrate H-D-Nva-CHA-Lys-pNA (pNA = para nitroanilide) and of NaCl (250 mmol/l final) a linear kinetic with delta A405/t in the range of 0.2/min for normal plasma was recorded. In an endpoint version of the test the chromogenic substrate can be added together with plasminogen resulting an A/t2-kinetic. Dilution studies showed a linear calibration curve from 0 to 14 arbitrary u-PA inhibiting units (AU)/ml plasma. By means of PAI-standard plasmas PAI-capacity values of 20 healthy volunteers (10 males/10 females) (x = 26 years, sigma = 4.2) were determined. They ranged from 0.4 - 6.9 (x = 1.3, sigma = 0.9) AU/ml plasma. Plasma samples containing more than 14 AU/ml were prediluted with PAI-deficient plasma. Intra- and inter-assay coefficients of variation (CV) were determined to be 1.3 +/- 0.6 and 4.3 +/- 0.5%, respectively. The values of this assay correlate well with those obtained by acidification of the samples. However, the possibility of measuring plasma PAI (and PA) activities by means of a simple and direct approach can be considered as an important progress with regard to routine hospital practice. The presented oxidative inactivation of A2-PI mimics the leukocyte attack phase, suggesting that activated leukocytes create a microenvironment of uncontrolled plasmin activity.

Adult

Effect of alcohol and glucose infusion on pituitary-gonadal hormones in normal females.

During 1 h, median 976 mmol ethanol in 5.5% glucose was administered i.v. to six healthy female volunteers (aged 26-37 years) in the luteal phase of the menstrual cycle. The median maximal blood ethanol concentration was median 33.5 mmol/l and serum ethanol concentrations of 2 mmol/l were reached after 8 h. Four of the women participated in a control experiment with infusion of an equal volume of glucose 5.5%. Venous blood samples were drawn 5 times during the 24-h follow up period. Serum concentrations of sex steroids and pituitary hormones decreased in both ethanol and control experiments and the results did not differ significantly. The lowest hormone concentrations were observed 1-5 h after the start of infusion. Oestradiol, oestrone and oestrone-sulphate concentrations decreased 24-46% compared to basal values. 5 alpha-dihydro-testosterone levels decreased 23-31%, androstenedione and dehydroepiandrosterone-sulphate levels decreased 6-48%, while testosterone levels did not change significantly. Prolactin concentrations were reduced by 41-51% of basal values and luteinizing hormone concentrations by 37-68% Follicle stimulating hormone levels did not change significantly. Stress factors or haemodilution are not likely explanations of the observed changes in hormone concentrations. A circadian rhythm could not explain changes in hormones of non-adrenal origin.

Adult

Thyroid hormones and thyroxine-binding globulin in relation to liver function and serum testosterone in men with alcoholic cirrhosis.

In 73 euthyroid male patients with histologically verified alcoholic cirrhosis, thyroid hormones, thyroxine-binding globulin (TBG) and testosterone concentrations (total, non-protein- and non-SHBG-bound) were studied in relation to each other and to the degree of liver dysfunction. Serum concentrations of triiodothyronine (T3) decreased significantly (p less than 0.05) and thyroid-stimulating hormone (TSH) increased with progressing liver dysfunction. Serum concentrations of tetraiodothyronine (T4), TBG and T4/TBG ratio did not correlate significantly with liver function. Serum T3 concentrations correlated significantly (Kendall Tau-beta = -0.33, p = 0.001) with total serum testosterone concentrations, while there was a negative correlation (Kendall Tau-beta = -0.20, p = 0.025) between testosterone and TSH values. No correlation was found between testosterone concentrations and serum levels of TBG. It is proposed that the association between T3 and TSH on one hand and testosterone concentrations on the other reflects a covariation of these variables with liver function. The TBG level was normal in most patients and was not correlated to testosterone concentrations.

Adult

Effect of the stable prostacyclin analogue iloprost on water and electrolyte transfer of the rat ileum and colon in vivo.

The effect of iloprost on water and ion transfer was measured simultaneously in tied-off loops of the rat ileum and colon in vivo. (1) In the ileal loops iloprost had no effect on water and ion transfer neither by intraluminal, nor intraaortal or intravenous application. (2) In the colonic loops only intraaortal bolus application of the high dose of 500 micrograms iloprost significantly decreased net water, sodium and chloride absorption, but did not induce net secretion. (3) Inhibition of endogenous prostaglandin synthesis by indomethacin did not change net water and electrolyte transfer in the ileum and colon. (4) Under this pretreatment i.v.-application of 100 micrograms iloprost, ineffective without indomethacin, induced a net secretion of water and sodium and inhibited absorption of chloride in the colon. (5) At the same time iloprost had no effect in the ileal loops of the same animals. (6) Potassium secretion was activated already by 100 micrograms iloprost administered intraluminally. We conclude from this study, that prostacyclin and iloprost have a specific secretory action in the colon. However this effect is masked under in-vivo conditions, either by interactions of ineffective prostaglandin metabolites with the concerned receptors or by counteracting prostaglandins, and becomes evident only after inhibition of the prostaglandin biosynthesis.

Animals

The effect of oral testosterone on serum TBG levels in alcoholic cirrhotic men.

Seventy-three euthyroid male patients with alcoholic cirrhosis of the liver were randomly allocated to oral testosterone (200 mg t.i.d.) or placebo and followed for up to 36 months. Triiodothyronine (T3), tetraiodothyronine (T4), thyroxine binding globulin (TBG) and T4/TBG ratio were determined before entry and during follow-up. No significant differences were observed before entry or during follow-up between the two treatment groups. T3, T4 and T4/TBG ratio did not change significantly during follow-up, while TBG concentrations decreased (P less than 0.05). Using a multivariate test, it is demonstrated that testosterone treatment significantly reduced TBG concentrations in cirrhotic men with preserved liver function, like normal men, but not in patients with moderate liver dysfunction. The lack of effect of testosterone in patients with more advanced cirrhosis may be due to a decreased function of sex hormone receptors in their liver.

Administration, Oral