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Biomedical subjects

J Bircher

Publications and source records attributed to J Bircher.

At least 127 records · Page 7Linked to original sources
PubMed1976

Defective renal handling of water in the rat with a portacaval shunt.

Male rats with a portacaval anastomosis, placed in metabolic cages excreted twice as much urine as unoperated control rats. After subcutaneous injection of one unit of pitressin tannate in oil, the rats on average exhibited a 27% reduction in fluid intake and a 37% reduction in urine volume. Nevertheless the rats still excreted 60% more urine than control rats. Fluid restriction resulted in a reduction in urine volume and an increase in urine osmolality in both groups of rats. Shunted rats, however, continued to excrete 49 ml.kg.(-1)24h-1, while drinking only 43 ml.kg.(-1)24h-1. Owing to the negative water balance plasma osmolality rose by 22 mosm/kg H2O. Two weeks after portacaval anastomosis arterial prostaglandin-E concentrations were 412 ng/1, compared to 158 ng/1 in control rats. The results are consistent with the idea, that the shunt induced diuresis may be due to the renal effects of prostaglandin-E.

Animals↗
PubMed1976

Aminopyrine demethylation measured by breath analysis in cirrhosis.

The method of measuring the rate of aminopyrine demethylation by breath analysis was assessed in 23 normal subjects and 20 patients with cirrhosis. Carbon 14 aminopyrine specifically labeled at the two N-methyl groups was administered by mouth in a dose of 9 mg/kg, including a total radioactivity of 2 muCi. The decay of the specific activity of 14CO2 in breath (kb) was found to correlate (r = 0.91) with the disappearance of aminopyrine from plasma (KP). In normal volunteers, kb was 22.4%/hr; in patients with alcoholic and nonalcoholic cirrhosis it was depressed to 8.4%/hr (p less than 0.001). The degree of functional impairment found with the breath test was similar to the sulfobromophthalein (BSP) disappearance curve and the galactose elimination capacity. Although many questions relating to the aminopyrine breath test remain open, our data confirm and extend previous studies of 14CO2 breath analysis after 14C-aminopyrine administration. It is concluded that it represents a simple and noninvasive procedure which quantitatively reflects the microsomal function of the cirrhotic liver.

Adult↗
PubMed1976

Gamma-glutamyltranspeptidase in the rat liver after portacaval shunt.

Gamma-Glutamyltranspeptidase (GGTP) activity was studied in livers of rats submitted to an end-to-side portacaval shunt (PCS) and in developing animals. To correlate the evolution of the enzymatic activity measured in vitro, histochemical techniques were used to localize enzyme activity in liver tissue. The GGTP activity in the adult rats was low and amounted to 2.0 +/- 0.1 mumol/min/g. During fetal development the enzyme activity rose beginning on the 15th gestational day from 630 +/- 97 to 1,058 +/- 20 on the first postnatal day. Then the values declined and reached nearly adult values from the 10th postnatal day. After PCS the GGTP activity exhibited a three- to sixfold increase (130 +/- 69 to 371 +/- 131) as compared with unoperated adult controls (53 +/- 13). the highest levels corresponded to those observed between the 3rd and 5th postnatal day in the developing rats. The histochemistry of GTTP in the fetal and newborn liver showed a regular distribution of the enzyme as a fine deposit in the hepatocytes throughout the whole tissue. Ten days after birth the activity was low, at the same level as in the adult rat. In the period after PCS hepatocytes began to show signs of enzymatic activity at the periphery of the hepatic lobules, which subsequently spread through the whole lobules. The increase of GGTP activity after PCS equaled the activity found in fetal animals. That correlated well in both groups with the reappearance of histologically demonstrable enzyme activity in hepatocytes.

Animals↗
PubMed1976

Expiratory measurement of maximal amino-pyrine demethylation in vivo: effect of phenobarbital, partial hepatectomy, protacaval shunt and bile duct ligation in the rat.

Current in vivo methods do not give information about the drug-metabolizing capacity (Vmax) and the affinity of the microsomal enzyme system for the drug i.e., the dose yielding Vmax/2 (Kd). To explore the possibility of estimating these variables from demethylation rates measured by 14CO2 exhalation, various doses of 14C-aminopyrine were injected i.v. to unanesthetized rats. Drug clearances based on 14CO2 exhalation agreed well with those derived from plasma disappearance rates. Evaluation of dose-response curves revealed saturation phenomena. In the normal rat, a Vmax of 173 nmol/min/100 g and Kd of 26 mumol/100 g could be calculated. Enzyme induction with phenobarbital increased Vmax to 745 nmol/min/100 g, whereas in the rat with portacaval shunt, it was reduced to 45 nmol/min/100 g. After 48-hour bile duct ligation, Vmax was not significantly different from the controls, but Kd increased to 36 mumol/100 g compatible with a competitive type of inhibition of aminopyrine demethylation. Two-thirds hepatectomy reduced Vmax by only 50% suggesting that a substantial portion of demethylation occurs extrahepatically. The approach presented appears to be a valid alternative to conventional plasma clearance methods allowing interpretation of some mechanisms affecting in vivo drug metabolism under various conditions.

Aminopyrine↗
PubMed1976

Hepatic functional deterioration after portacaval shunt in the rat. Effects on sulfobromophthalein transport-maximum, indocyanine green clearance and galactose elimination capacity.

The consequences of a portacaval shunt on liver function were studied in male Sprague-Dawley rats. Fourteen days after an end-to-side portacaval anastomosis the galactose elimination capacity and the plasma clearance of indocyanine green were reduced in proportion to the approximately 50% loss in liver mass. The biliary transport maximum for sulfobromophthalein, on the other hand, decreased by almost 70% from 153 to 52 nmoles per min per min per 100 g after portacaval anastomosis. This reduction of sulfobromophthalein excretion was accompained by a significant decrease in the hepatic conjugation of the dye to glutathione. Our findings demonstrate that a quantitative and qualitative functional deterioration of previously normal livers results from portal blood deprivation.

Animals↗
PubMed1976

A new look at the plasma disappearance of sulfobromophthalein (BSP): correlation with the BSP transport maximum and the hepatic plasma flow in man.

In order to improve the clinical usefulness of the plasma disappearance curve of sulfobromophthalein (BSP), its components were analyzed in 26 control subjects, in 28 patients with cirrhosis, and in 13 cases of miscellaneous liver abnormalities. The uncorrected initial disappearance rate (ki) was found to discriminate best between the control and the patient groups. The second exponential component (k2) was linearly correlated with the transport maximum (Tm) on a double logarithmic plot, but appeared to be independent of the estimated hepatic plasma flow (EHPF). An interpretation of this relationship was possible, when based on a model having saturation kinetics for biliary excretion. The first exponential component (ki) appeared primarily determined by hepatic perfusion. These relationships may contribute to a better understanding and more rational use of dye excretion tests as measures of hepatic function. The data also add to our knowledge about the nature of the excretory defect in cirrhosis.

Adult↗
PubMed1975

Pyritinol hydrochloride and cognitive functions: influence on children in slow learner classes.

Pyritinol-HCl was tested for its impact on the cognitive functions of children with learning disabilities. This study is a contribution to scientific discussion on the complicated methodologic problems in evaluating the clinical efficacy of psychopharmacologic agents. Sixty-seven pupils of slow learner classes between the ages of 11 and 16 years were treated for 6 months with 300 mg pyritinol-HCl/24 hr or placebo under strict double-blind conditions. Drug intake was stimulated and controlled by means of intense psychosocial interaction with the mothers of the subjects. The dependence variables used to test medication effects were 22 parameters of cognitive performance measured in psychologic tests for perceptual and intellectual functions which were administered immediately before and after the medication phase. First the gainscores before and after treatment with pyritinol or placebo within the 22 cognitive parameters were statistically compared. In addition, an analysis of covariance on the corrected results of the second test (treating the results of first testing as covariates) and a two group discriminant analysis for overall differences were performed. None of the 22 parameters showed statistically significant treatment effects with respect to average performance (t (pyritinol - placebo) = 1.96 to 1.31), neither could the two groups be separated by discriminant analysis (Hotelling's T2 = 35.4, df - 22 and 43, P = 0.465). With respect to a variability of gainscores, however, in four parameters there was a significantly higher variance in the pyritinol group (F = 1.85-2.33, P less than 0.05, less than 0.02, respectively). This fact may signify that pyritinol-HCl had different effects on different subjects. By means of prognostic stratification we therefore attempted to define objective criteria for a selection of subjects with probable positive treatment effects. None of the 15 tested criteria, such as body weight, age, perceptual handicaps, or reduced short term memory, IQ range, proved, however, to be critical for a prognosis of pyritinol effects within the present test population.

Adolescent↗
PubMed1974

A practical approach to quantitate hepatic excretory function.

A statistical comparison of different BSP tests was carried out in normal subjects and in patients with various degrees of chronic liver damage. Only the logarithm of the BSP retention correlated linearly with the physiologically more meaningful determination of the maximal excretory capacity of the liver (BSP Tm, Wheele's method). A double logarithmic transformation was required to correlate the second exponential component of the BSP plasma disappearance curve (k(2)) with the BSP Tm. When the limitations of these methods are kept in mind, the observed statistical relationships can be used to express hepatic functional deterioration in more physiological terms.

Humans↗