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Biomedical subjects

R Preisig

Publications and source records attributed to R Preisig.

126 records · Page 7Linked to original sources
PubMed1967

Experimental viral hepatitis in the dog: production of persistent disease in partially immune animals.

Experimental infection with canine hepatitis virus has been studied in a series of 49 dogs. The pattern of response to infection was distinctly modified by the immune status of the animal. All of 19 fully susceptible dogs had an acute, fulminating fatal hepatitis when infected with a standard dose of virus, and all of 19 dogs with high levels of immunity to the virus survived without apparent illness. However, 11 dogs were spontaneously encountered with partial immunity to the infectious agent, and these animals developed different, prolonged forms of hepatitis following infection. In four animals death occurred in 8-21 days following what may be called a subacute course. The remaining seven dogs survived up to 8 months with evidence of chronic hepatic damage. The subacute and chronic forms of hepatitis were reproduced experimentally in seven of eight fully susceptible dogs which were passively immunized against the canine hepatitis virus by administration of hyperimmune serum. Although the virus could be found in sites of hepatic damage in the early stages of the subacute and chronic diseases, it could not be demonstrated in the later stages which were characterized by persistent hepatic damage and a marked chronic inflammatory reaction. Dogs with chronic hepatitis eventually developed extensive hepatic fibrosis. The pathologic, physiologic, virologic, and immunologic features of these experimental forms of viral hepatitis are described.

Animals↗
PubMedDate not supplied

Abnormal glucuronidation of zomepirac in patients with cirrhosis of the liver.

The disposition of zomepirac was investigated in 18 patients with various liver diseases and in 10 healthy normal subjects in order to further test the hypothesis that glucuronidation of drugs may be spared in liver disease. Severity of the liver disease was assessed by the galactose elimination capacity. Following oral administration of zomepirac (200 mg), plasma and urinary drug concentrations were measured by high-pressure liquid chromatography. Urine was assayed before and after alkaline hydrolysis. The apparent oral clearance of zomepirac was 3.7 +/- S.D. 1.2, 3.0 +/- 0.8, and 1.8 +/- 0.6 ml . min-1 . kg-1 in normal subjects, patients with mild liver disease, and cases with cirrhosis, respectively. In patients with liver disease, the reduction in zomepirac clearance was significantly correlated with the abnormalities in galactose elimination capacity (r = 0.83, n = 18), suggesting that the functioning liver cell mass was the major determinant of the rate of zomepirac disposition. These results are not consistent with the original hypothesis but suggest that--in contrast to ether-glucuronidation--ester-glucuronidation may be abnormal in liver disease. Dosage adjustments may, therefore, be necessary in patients with cirrhosis of the liver.

Adult↗
PubMedDate not supplied

Caffeine: a model compound for measuring liver function.

The effects of liver disease on caffeine plasma clearance (Cl) and on exhalation of 14CO2 following i.v. injection of 2 mu Ci of [3-methyl-14C]caffeine together with 125 mg of the unlabeled compound were measured in 15 patients with cirrhosis, 11 subjects with miscellaneous liver disease, and 10 normal volunteers. Compared to mean values for Cl (2.02 +/- S.D. 0.68 ml per min per kg) and t1/2 (3.8 +/- 0.9 hr) in normal volunteers, cirrhotics were characterized by highly significant reductions in Cl (to 0.76 +/- 0.40) and prolongation in t1/2 (to 13.7 +/- 13.0), whereas the volume of distribution (VD) remained relatively unchanged (0.57 +/- 0.16 vs. 0.64 +/- 0.13 liter per kg in normals). Cumulative 14CO2 production and specific activity of 14CO2 in breath decreased in parallel (r = 0.83) with Cl. Patients with miscellaneous liver disease exhibited only small changes in Cl and t1/2; however, 14CO2 parameters in breath appeared more sensitive in indicating the slight functional derangement. In view of the correlation (Rs = 0.83) of cumulative 14CO2 excretion with the initial disappearance constant for bromosulfophthalein, the caffeine breath test may be considered as a quantitative measure of hepatic microsomal activity; based on a surprisingly close, hyperbolic relationship between Cl and fasting caffeine plasma concentrations, the latter might serve as a simple guide to severity of liver disease.

Adult↗
PubMedDate not supplied

Overnight salivary caffeine clearance: a liver function test suitable for routine use.

The feasibility of measuring caffeine clearance from saliva (SCl) was assessed in ambulatory patients with liver disease and in a control group, and the results were compared with quantitative liver function tests. For this purpose, the subjects were given 280 mg caffeine p.o. in decaffeinated coffee powder between noon and 4 p.m., and caffeine concentrations were measured in saliva (using an enzyme immunoassay) before bedtime and upon arising. In the cirrhotics (n = 29), SCl was 0.58 +/- S.D. 0.45 ml per min X kg, thus being reduced to approximately one-third of drug-free, nonsmoking controls (1.53 +/- 0.46, n = 18); although patients with noncirrhotic liver disease showed intermediate values (0.95 +/- 0.47), their reduction in SCl was significant (p less than 0.001). SCl was correlated with indocyanine green fractional clearance, galactose elimination capacity and aminopyrine breath test; however, the closest relationship (Rs = 0.80) was observed with the aminopyrine breath test. It is suggested that the measurement of SCl represents a noninvasive and innocuous procedure for quantifying hepatic microsomal function, and is suitable for routine use. Since a.m. saliva concentrations of caffeine are highly correlated (Rs = -0.94) with SCl, further simplification of the test to a single-point measurement appears possible.

Ambulatory Care↗
PubMedDate not supplied

Use of salivary levels to predict clearance of caffeine in patients with cystic fibrosis.

The quantification of liver function is possible using the approach of salivary caffeine clearance. Hepatopathy sometimes complicates cystic fibrosis (CF), thus suggesting the use of this diagnostic tool in CF as well. Since in CF some compounds are poorly absorbed or abnormally metabolized, and the function of salivary glands or renal tubuli partly impaired, caffeine was measured in urine, blood, and saliva after a single oral dose of 3 mg/kg in CF patients. The urinary excretion rate of caffeine was normal in five CF patients. The caffeine levels in plasma or saliva, measured 4 to 5 h and 16 to 17 h after caffeine intake, were normal in 34 nonhepatopatic CF patients. The calculated salivary caffeine clearance was comparable in the 34 nonhepatopatic CF patients (1.88 +/- 0.46 ml/min/kg) and in the control group (1.88 +/- 0.44 ml/min/kg). In CF patients, no correlation was found between caffeine clearance and body weight, height, relative underweight, dosage of pancreatic enzymes, or Chrispin-Norman x-ray score. The salivary caffeine clearance was reduced in seven hepatopathic CF patients (1.32 +/- 0.63 ml/min/kg, p less than 0.01); nevertheless, the salivary caffeine clearance was reduced (boundary line at 1.1 ml/min/kg) in three CF patients with proven liver cirrhosis but not in four with hepatosplenomegaly and altered liver tests. These data indicate an unaltered caffeine metabolism in CF and open the way for the use of this diagnostic procedure in CF as well. This test might be valuable in CF patients with clinical or laboratory findings suggesting liver involvement.

Adolescent↗
PubMedDate not supplied

The disulfiram-alcohol reaction: factors determining and potential tests predicting severity.

13 ambulatory alcoholics (3 women, 10 men) who consented to alcohol-aversive treatment with disulfiram were subjected to detailed investigations before, during, and after the disulfiram-alcohol reaction (DAR). The studies included quantitative estimation of liver function (aminopyrine breath test, ABT; galactose elimination capacity, GEC) prior to the DAR, measurement of alcohol and acetaldehyde plasma levels together with pulse rate and blood pressure during the DAR, and the effects of disulfiram on erythrocyte acetaldehyde-oxidizing capacity (AOC). As expected, the severity of the DAR showed considerable interindividual variation. However, the maximal fall in diastolic blood pressure was closely (r = 0.83; p less than 0.001; n = 13) related to peak acetaldehyde plasma level (AAPL). The decrease in systolic blood pressure was age dependent, individuals greater than 40 years exhibiting a larger drop for a given AAPL. The dependence of acetaldehyde formation on liver function was suggested by a significant correlation (r = 0.88; p less than 0.01; n = 8) between ABT and AAPL; this relationship was influenced by the prior intake of enzyme-inducing drugs. Measurements of AOC indicated that a disulfiram-induced maximal suppression is achieved already after 6 days of treatment reaching levels of 0.7 +/- 0.6 nmol/ml/min (SD) (compared to pretreatment values of 4.1 +/- 0.9). Mean values in untreated alcoholics and in subjects with alcoholic or nonalcoholic liver disease were not significantly different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗