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Biomedical subjects

S Schenker

Publications and source records attributed to S Schenker.

At least 181 records · Page 10Linked to original sources
PubMed1977

Disposition of nafcillin in patients with cirrhosis and extrahepatic biliary obstruction.

Nafcillin, a semisynthetic penicillin effective against penicillinase-producing staphylococci, is eliminated largely in man via the liver. This study assessed the effect of cirrhosis and extrahepatic biliary obstruction in man on the pharmacokinetics of nafcillin. The plasma clearance of nafcillin controls was 583 +/- 144.2 ml per min (mean +/- SD) and fell strikingly to 291 +/- 147.6 and 163 +/- 56.3 ml per min in patients with cirrhosis and extrahepatic obstruction, respectively (P less than 0.001). In the latter two groups nafcillin excreted in urine increased from about 30 to 50% of administered dose (P less than 0.02), suggesting that renal disease superimposed on hepatic disease would further decrease over-all nafcillin clearance. The depression of nafcillin clearance with hepatobiliary disease did not correlate with any conventional liver laboratory test. The initial volume of distribution of nafcillin (V1) was unaltered but at steady state (Vd()) there was a significant reduction in the distribution volume in the patients with liver disease. Accordingly, the impairment in drug elimination, as assessed by its clearance from plasma, was underestimated by the prolongation of the nafcillin elimination half-life (t1/2(beta)) which was 1.02 +/- 0.20 hr in controls, and 1.23 +/- 0.31 (P greater than 0.05) and 1.73 +/- 0.44 hr (P less than 0.03), respectively, in patients with cirrhosis and extrahepatic obstruction.

Adult↗
PubMed1976

Thiamine transport in thiamine-deficient rats. Role of the unstirred water layer.

As part of a systematic study of alcoholism and thiamine absorption, the effect of diet-induced thiamine deficiency and the role of the unstirred water layer on the thiamine transport were investigated. Using 3H-labeled dextran as a marker of adherent mucosal volume, jejunal uptake of 14C-labeled thiamine hydrochloride was measured, in vitro, in thiamine-deficient rats and pair-fed controls. Uptake of low thiamine concentrations (0.2 and 0.5 muM) was greater in the thiamine-deficient rats than in the controls. In contrast, uptake rates for high thiamine concentrations (20 and 50 muM) were similar in both groups. While Jmax was unaltered, Km was decreased in thiamine deficiency, suggesting a decrease in unstirred water layer thickness. Accordingly, the thickness of the water layer was measured in both groups of animals and correlated with Jmax and Km under unstirred and stirred conditions. Without stirring, there was no difference in Jmax between the two groups. In contrast, both Km and the water layer were reduced in the thiamine-deficient rats. With stirring, Jmax was not affected, but both Km and the water layer thickness were reduced to similar values in both groups. Reversal of thiamine deficiency resulted in the return of thiamine uptake and the unstirred water layer thickness to control values. These data support the concept of a dual system of thiamine transport and emphasize the role of the unstirred water layer as an important determinant of transport kinetics not only under physiologic situations but also in diet-induced rat thiamine deficiency, a model for a clinical patholigical state. The decrease in the unstirred water layer thickness in thiamine deficiency may be also viewed as a possible adaptive mechanism to facilitate absorption of meager supplies of thiamine.

Animals↗
PubMed1976

Gastric and biliary excretion of meperidine in man.

The role and importance of enterogastric secretion in the disposition and elimination of the weak base, meperidine (pKa 8.63), was studied after intravenous administration (50 mg) of the drug to 6 normal volunteers. Continuous collection of the gastric fluid over a 4-hr period demonstrated the establishment of high gastric fluid/plasma concentration ratios for meperidine (mean about 50, range, 10 to 200). However, the total amount of drug recovered, even after correction for incomplete collection, was only a small percentage of the administered dose. Under basal conditions a mean +/- SE of 1.9 +/- 0.3 mg, equivalent to 3.7% of the administered dose, was found in the total gastric aspirate. Stimulation of gastric secretion by subcutaneous injection of betazole (1.5 mg/kg) increased this recovery to 3.6 +/- 0.3 mg (7.2%) primarily due to the increase in gastric volumen output. Aspiration of the gastric fluid in either the basal or stimulated situation had no observable effect upon the plasma concentration/time profile of meperidine whether assessed by the terminal half-life, t 1/2 beta, or the plasma clearance; control values were 3.8 +/- hr and 1,190 +/- 130 ml/min, respectively. In 2 subjects "bile fluid" was also collected for 2.5 hr and found to contain less than 0.2% of the administered dose. Enterosystemic recycling is therefore of minor importance in the disposition and elimination of meperidine in man.

Adult↗
PubMed1976

Liver-lung scan in the diagnosis of right subphrenic abscess.

To assess the value of liver-lung scanning in the diagnosis of right subphrenic abscess, 148 scans were reviewed against corresponding charts. Of 91 scans with adequate clinical data, overall scanning error was 19.3% with 14 false positive and 3 false negative scans. Among 49 scans (of the initial group of 91 studies) with presence or absence of actual pathology proved by surgery and/or autopsy, there were 3 true positive, 12 false positive, 29 true negative, and 3 false negative scans. Analysis of data indicated (1) lower accuracy of scan interpretations than generally reported, (2) low specificity for positive scans and high specificity for negative scans, (3) correlations of false interpretations with atypical degrees of liver-lung separation and with scanning defects in liver and lung, and (4) failure of rereading significantly to improve accuracy of interpretation.

Angiography↗
PubMed1976

A prospective study to determine the efficacy of antibiotics in acute pancreatitis.

This study is a double "blind" prospective evaluation of the efficacy of antibiotics (Ampicillin) in the treatment of acute alcohol-induced and idiopathic pancreatitis. Fifty-eight patients with acute pancreatitis were randomly divided into antibiotic and non-antibiotic treatment groups. The two groups were comparable clinically at the onset of the study and other than for antibiotics received identical therapy. The patients without antibiotics had a clinical course equal or slightly more favorable than the antibiotic treatment group in all parameters examined. These data indicate that prophylactic use of Ampicillin is not indicated in patients with routine acute alcohol-induced or idiopathic pancreatitis. The role of prophylactic antibiotics in patients with pancreatitis related to biliary calculi and those with more severe varieties of acute hemorrhagic or necrotizing pancreatitis remains to be more clearly defined.

Acute Disease↗
PubMed1976

Amylase--its clinical significance: a review of the literature.

This review of the English literature on amylase was undertaken because no recent discussion of the subject could be located, no comprehensive list of disorders causing hyperamylasemia or hyperamylasuria is available, and several major advances in the area have been made, notably the amylase isoenzyme determination and Cam/Ccr ratio. Several important concepts have emerged from this review. First, hyperamylasemia and hyperamylasuria are not specific indices of the presence of pancreatic disease or damage. Second, serum and urinary amylase levels can be spuriously normal with hypertriglyceridemia and pancreatitis. Third, the current emphasis on diagnostic methods for measuring serum amylase isoenzymes promises to improve the specificity of this determination. It will also enhance our understanding of the sources, distribution, metabolism, and elmination of amylase. Fourth, the development of the Cam/Ccr ratio may provide a practical diagnostic tool for separating clinically significant hyperamylasemia due to pancreatitis from that caused by other factors. Both the the isoamylase determination and Cam/Ccr ratio clearly require future research to place their clinical application in the proper perspective.

Amylases↗
PubMed1976

Normal disposition of oxazepam in acute viral hepatitis and cirrhosis.

Oxazepam (Serax) is a tranquilizer-sedative of the benzodiazepine group that is predominantly metabolized to a pharmacologically inactive glucuronide and subsequently excreted by way of the kidneys. We administered this drug as a single oral dose to seven patients with acute viral hepatitis, to six with cirrhosis, and to age-matched control subjects. Elimination half-life (T1/2) and the apparent oral plasma clearance for the drug in patients with hepatitis and cirrhosis were comparable to values obtained in age-matched controls (P greater than 0.05). In addition, the apparent volume of distribution of oxazepam, its plasma binding, blood/plasma ratio, and the rate of urinary excretion of oxazepam, predominantly as the glucuronide, were comparable (p greater than 0.05) in the two groups of patients with liver disease and their respective controls. Unlike many other sedatives, oxazepam is eliminated normally in patients with parenchymal liver disease an therefore, on pharmacokinetic grounds, seems to be an excellent sedative for use in such persons.

Acute Disease↗
PubMed1976

Abnormal regulation of plasma pyridoxal 5'-phosphate in patients with liver disease.

UNLABELLED: Pyridoxal 5'-phosphate (PLP), the coenzyme form of vitamin B6, is essential for many biochemical reactions in the body. Studies in experimental animals have suggested that the liver is a primary site for the formation of PLP circulating in the plasma, and that it may also participate in its degradation. This study evaluates, for the first time, the effects of liver disease in man on the regulation of plasma PLP. The plasma PLP level was measured before and sequentially after the rapid intravenous administration of 50 mg of pyridoxine to patients with alcoholic cirrhosis, acute hepatitis, and extrahepatic obstruction, and to normal control subjects. The base line plasma PLP concentration was significantly lower in cirrhotic patients than in normal persons (P less than 0.025), and there was a tendency for it to be reduced in patients with extrahepatic obstruction. After administration of pyridoxine there was a significant increase in the plasma PLP level over a 2- to 12-hr period, after which the concentration returned gradually toward the initial value. The area under the concentration/time curve was from 2 to 8 times smaller (P less than 0.002) in the patients with liver disease. To assess possible mechanisms of this change, 5 mg of PLP were intravenously administered to the various patient groups and the pharmacokinetics of the disposition were assessed. The initial and steady state volumes of distribution of PLP were comparable in cirrhotics and controls (P greater than 0.05), but the clearance of plasma PLP in cirrhotics was much faster (63.0 +/- 7.4 versus 31.7 +/- 2.7 ml per min, P less than 0.004). Similar findings were obtained in the other liver disease subjects. The in vitro plasma binding of PLP at supracirculatory concentrations was comparable in cirrhotics and controls (99.4 versus 99.5%, P greater than 0.05). IN CONCLUSION: (1) plasma PLP regulation in patients with liver disease is abnormal, (2) a significant factor in the decrease in plasma PLP after intravenous pyridoxine administration in these patients appears to be an increase in the total plasma clearance of the coenzyme, and (3) it is postulated that this may be due to increased degradation of PLP by the diseased liver.

Acute Disease↗
PubMed1975

The effect of cirrhosis on the disposition and elimination of clindamycin.

This study assessed the effect of alcoholic cirrhosis in man and of experimental liver injury in rats on the disposition and elimination of clindamycin. In 7 cirrhotics a statistically significant, although modest, prolongation of clindamycin half-life (T1/2beta) was observed as compared to values in 7 age-matched normal contrals (mean plus or minus SD: 4.46 plus or minus 0.93 hr vs 3.42 plus or minus 0.45 hr, P equals 0.02). This was primarily due to a decrease in clindamycin serum clearance in the cirrhotics, since the volume of distribution of the drug was similar in both groups (P more than 0.05). Serum protein binding of clindamycin was of the order of 79% and was comparable in both groups (P more than 0.05). There was a significant correlation between the T1/2beta of the drug and both total serum bilirubin and SGOT. The T1/2beta of clindamycin was also prolonged in rats with acute hepatic necrosis induced by administration of carbon tetrachloride and those with acute cholestasis caused by common bile duct ligation. These data suggest that liver damage, both chronic and acute, impairs the elimination of clindamycin but that this effect is small.

Adult↗
PubMed1975

The effects of age and liver disease on the disposition and elimination of diazepam in adult man.

This study investigates the separate effects of age and hepatocellular liver disease on the disposition and elimination of diazepam (Valium) in man. The drug was given either by rapid intravenous injection (0.1 mg/kg) or orally (10 mg) to 33 normal volunteers rnaging in age from 15 to 82 yr as well as to 9 individuals with alcoholic cirrhosis, 8 with acute viral hepatitis, and 4 with chronic active hepatitis. In the normal individuals, the terminal plasma half-life of diazepam, (t 1/2 (B)) exhibited a striking age-dependence; at 20 yr the t 1/2 (beta) was about 20 h, but it increased linearly with age to about 90 h at 80 yr. The plasma clearance of diazepam in the majority of the normal subjects was between 20 and 32 ml/min and showed no significant age-dependence. Cigarette smoking did not affect the half-life or the clearance. Additionally, neither the plasma binding (97.4 plus or minus 1.2%, mean plus or minus SD) nor the blood/plasma concentration ratio (0.58 plus or minus 0.16) of diazepam showed any age-related changes (P greater than 0.05). By contrast, analysis of the intravenous data according to a two-compartment open model indicated that both the initial distribution space (V1) and the volume of distribution at steady state [Vd(ss)] of diazepam increased linearly with age (P less than 0.005). The increase in Vd(ss) was secondary to the change in V1. It appears then that the prolongation of t 1/2 (beta) of diazepam with age is primarily dependent on an increase in the initial distribution volume of the drug. The plasma concentration/time course of the metabolite, desmethyldiazepam, was also affected by age. In older individuals, the initial presence and the peak values of desmethyldiazepam were observed later and the metabolite was present in lower concentrations. Despite the profound prolongation of t 1/2 (theta) with age, the constancy of diazepam clearance indicates that drug plasma concentrations will not accumulate any more in the old than the young, and chronic dosage more in the old than the young, and chronic dosage modifications based on pharmacokinetic considerations are unnecessary. Data obtained in patients with liver disease were compared with those found in age-matched control groups. Patients with cirrhosis showed a more than twofold prolongation in the half-life of diazepam (105.6 plus or minus 15.2 vs. 46.6 plus or minus 14.2 h, P less than 0.001).

Administration, Oral↗
PubMed1975

Bacteremia with upper gastrointestinal endoscopy.

Fifty patients undergoing upper gastrointestinal fiberoptic endoscopy were studied prospectively for the development of bacteremia by aerobic and anerobic blood cultures obtained before, during, and at 5 and 30 minutes after the procedure. Forty-six patients were culture negative; four had positive cultures at 5 or 30 minutes after the procedure, or at both times. The level of bacteremia as estimated by pour plates was very low. Bacteremia did not correlate with the performance of biopsy or the type of mucosal abnormality found. It is concluded that only very high-risk patients should receive antimicrobial prophylaxis before this procedure. The minor risk of this low-level bacteremia should not be considered a contraindication to the performance of upper gastrointestinal endoscopy.

Duodenal Diseases↗
PubMed1975

Thiamine transport across the rat intestine. I. Normal characteristics.

The characteristics of normal thiamine transport across the intestine were studied in rats using intact intestinal loops and everted jejunal segments. In vivo studies with [35-S]-thiamine hydrochloride revealed, in all segments of small intestine, saturation kinetics for low thiamine concentrations (0.06 to 1.5 muM), but a linear relationship between high concentrations (2 to 560 muM) and absorption. Moreover, in vitro studies of net transmural flux using everted jejunal sacs demonstrated movement of [14-C]-thiamine hydrochloride against a concentration gradient only when low, but not when high, thiamine concentration was used, so that the serosal to mucosal ratio became significantly greater than the initial value of one. Pyrithiamine, 2 muM, dinitrophenol, 200 muM, norethylmaleimide, 100 muM, and ouabain, 10 muM, reduced the net transmural flux of 0.2 muM thiamine. In contrast, these inhibitors had no effect on 20 muM thiamine. When unidirectional flux across the jejunum was measured, saturation kinetics was again demonstrated for low thiamine concentrations. This phenomenon, however, was abolished by the addition of pyrithiamine, which exerted competitive inhibition on thiamine absorption. Anoxia and sodium lack reduced intestinal uptake of 0.5 muM thiamine to 58% and 74% of normal, respectively, but did not affect uptake of 50 muM thiamine. Lowering the marked with low thiamine concentrations (O10, 1.648) than with high concentration (Q10, 1.127). Stirring of the water layer reduced Km to 59% of unstirred value, while Vmax and permeability coefficient remained unchanged. Finally, movement of low concentration thiamine against an electrical gradient was observed under conditions of electrical short circuiting and zero potential difference. In contrast, no such effect was seen with high concentrations. These studies suggest that there exists in the rat a dual system of intestinal thiamine transport. At low concentrations, thiamine is absorbed by an active process; at high concentrations, transport across the intestine is largely a passive movement.

Animals↗