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Biomedical subjects

A L Baker

Publications and source records attributed to A L Baker.

At least 91 records · Page 5Linked to original sources
PubMed1982

The caffeine CO2 breath test: dose response and route of N-demethylation in smokers and nonsmokers.

The optimal conditions for performing the caffeine CO2 breath test (CBT) were investigated in smokers and nonsmokers. Caffeine labeled with 13C or 14C in all three (1, 3, and 7) methyl groups or specifically in the 1-, 3-, or 7-methyl groups were orally administered to healthy adults and the expiration of labeled CO2 was measured for 8 or 24 hr. The absolute rate of labeled CO2 excretion from trilabeled caffeine was proportional to the dose up to 3 mg/kg in all subjects. In smokers, the rate of labeled CO2 excretion averaged twice that in nonsmokers at all doses. A correlation was observed between the 2-hr cumulative CO2 excretion from trilabeled caffeine and the apparent oral metabolic clearance rate (MCR) of caffeine (R = 0.90). Monolabeled CBTs in smokers and nonsmokers demonstrated that 80% +/- 4% of labeled CO2 expired in the breath during the first 2 hr of a trilabeled CBT was derived from the 3 position; at 6 to 8 hr equal amounts were derived from the 3 and 7 positions. Little N-demethylation was observed from the 1 position at any time during the 8-hr test. The results indicate that the 2-hr cumulative excretion of labeled CO2 could be used to accurately predict the metabolic clearance rate of caffeine is the best CBT parameter for detecting the effect of smoking on caffeine N-demethylation. The data suggest that the primary routes of caffeine metabolism are 3-N-demethylation and ring hydroxylation and confirm that caffeine metabolites are N-demethylated primarily in the 3 and 7 positions.

Adult↗
PubMed1982

Effect of somatostatin on determinants of bile flow in unanesthetized dogs.

Seven dogs each underwent cholecystectomy, ligation of the accessory pancreatic duct, and insertion of a Thomas duodenal cannula opposite the ampulla of Vater. After full recovery, bile secretions were studied in the unanesthetized dogs by opening the cannula and placing a ureteric catheter through the papilla into the common bile duct. All animals received, throughout study, constant infusions of taurocholic acid to replace losses caused by interruption of the enterohepatic circulation and 14 C-erythritol for measurement of erythritol clearance. After bile flow stabilized somatostatin 800 ng/kg/minute was infused for 100 minutes and bile flow declined from 3.0 +/- 0.7 ml/10 minutes (SD) to 1.19 +/- 0.47 ml/10 minutes (p less than 0.001) and 14C-erythritol clearance fell from 3.6 +/- 1.14 to 1.77 +/- 0.43 ml/10 minutes (p less than 0.001). Bile salt output was unchanged, indicating that somatostatin inhibited bile salt-independent canalicular flow (BSICF). In other experiments animals underwent intraduodenal acidification which resulted in a marked increase in bile flow. Somatostatin infusion again causes a sharp fall in bile flow (p less than 0.05) suggesting that somatostatin also inhibited ductular flow. Infusion of somatostatin did not inhibit choleresis produced by exogenous secretin administration. Thus, somatostatin inhibits 1) ductular flow by inhibiting secretin release and 2) BSICF by a direct effect or by decreasing the release of hormones which induce canalicular flow.

Animals↗
PubMed1982

The aminopyrine breath test as a measure of liver function. A quantitative description of its metabolic basis in normal subjects.

The APBT is used widely as a measure of liver function. The development of the APBT into a liver function test of greater diagnostic value requires quantitative information on the processes involved in aminopyrine disposition and metabolism in man and on how APBT values reflect changes in these processes. A dual-isotope kinetic study of aminopyrine disposition and metabolism has been carried out on five normal adult subjects. Oral administration of 13C-aminopyrine (2 mg/kg) accompanied by simultaneous intravenous injection of 14C-aminopyrine was followed by serial measurements of aminopyrine and monomethylaminopyrine in plasma and urine over 6 hr. Timed collections of respiratory CO2 were analyzed for the content of excess 13CO2 and for 14CO2. On separate days, an intravenous bolus of 13C-labeled NaHCO3 was administered to obtain estimates of the kinetic parameters of CO2 elimination in each subject. These data were fitted simultaneously to a multicompartmental model that, in addition to providing hitherto unavailable quantitative information, has revealed that (1) demethylation is the major elimination pathway for aminopyrine; (2) a major alternative pathway not involving demethylation exists for monomethylaminopyrine; and (3) only 50% of the labeled carbon generated by demethylation eventually is oxidized to HCO3-. The sensitivity of seven types of APBT scores to 50% reductions in the rates of aminopyrine absorption, metabolism of monomethylaminoantipyrine, intermediate carbon metabolism, and bicarbonate kinetics was evaluated with breath test curves simulated using the APBT model. Every APBT score currently in use was affected by variations in both gastrointestinal output of aminopyrine and bicarbonate kinetics. There is a need for further development of selective scoring methods in the aminopyrine breath test.

Adult↗
PubMed1981

Hemorrhage from ileal varices after total proctocolectomy.

We report two cases of hemorrhage from ileal varices developing after total proctocolectomy for chronic ulcerative colitis. Intermittent peristomal bleeding preceded life-threatening hemorrhage from tru ileal varices proximal to the stoma. Management by portacaval shunting was effective and has not resulted in encephalopathy.

Adult↗
PubMed1981

Alcoholic hepatitis: update on recognition and management.

Alcohol consumption can cause fatty infiltration of the liver and more serious liver disorders such as alcoholic hepatitis and cirrhosis. The primary care physician familiar with the signs and symptoms can quickly institute corrective and sometimes lifesaving measures in affected patients. Management consists of detoxification, alcoholism rehabilitation, nutritional repletion, and treatment for any complications of the liver disease. In addition, several drugs now under study offer promising new approaches to treatment.

Hepatitis, Alcoholic↗
PubMed1981

A randomized clinical trial of insulin and glucagon infusion for treatment of alcoholic hepatitis: progress report in 50 patients.

A randomized, double-blind, controlled trial of insulin and glucagon infusion was conducted in 50 patients with acute alcoholic hepatitis. Twenty-five treatment patients received 24 U regular insulin and 2.4 mg glucagon over 12 h daily for 3 wk. Twenty-five control patients received 200 ml dextrose solution in identical bottles over the same time period. Six control and 2 treatment patients died from liver failure during study, and another treatment patient died from hypoglycemia. In the 34 patients with prothrombin times greater than 3 s prolonged, fewer deaths occurred among the insulin- and glucagon-infused patients (p less than 0.10). Clinical features of liver disease on entry into the study were similar in the two groups, and total serum bilirubin and prothrombin time improved more rapidly in the treatment group (p less than 0.05). Insulin and glucagon infusion is a promising treatment of alcoholic hepatitis and merits further study in the most severely ill patients.

Adult↗
PubMed1980

Sodium salicylate: effect on determinants of bile flow and cholesterol solubility in rhesus monkeys.

To study the mechanism of salicylate-induced choleresis in rhesus monkeys, we utilized animals with indwelling common bile duct catheters under phencyclidine anesthesia. Bile flow, [14C]erythritol clearance (an estimate of canalicular flow), and bile acid secretion were measured during baseline and for 1 1/2 hr during salicylate infusion. Bile flow increased from 91.2 +/- 7.3 ml/24 hr (SEM) to 180.1 +/- 8.0 ml/24 hr (P less than 0.001) with salicylate infusion and [14D]erythritol clearance from 114.5 +/- 8.9 ml/24 hr to 222.3 +/- 10.7 ml/24 hr (P less than 0.001), but bile acid secretion was unchanged, suggesting increased bile acid-independent canalicular bile flow. Salicylate concentration in bile averaged 1.48 +/- 0.08 mmol/liter, and salicylate concentration in extra bile produced by salicylate was unlikely to result in chloeresis of the magnitude observed. [3H]inulin bile-plasma ratios, measured in these same studies, were unchanged after salicylate administration, suggesting that permeability of the biliary tree was not altered. Bile lipid secretion, like bile acid secretion, was unchanged after salicylate administration, so no change occurred in the lithogenic index of the bile. These results demonstrate that salicylate is a potent choleretic in rhesus monkeys because of enhancement of bile acid-independent bile flow. Salicylate produced no change in the lithogenic index of the bile.

Animals↗
PubMed1980

Aminopyrine N-demethylation: a prognostic test of liver function in patients with alcoholic liver disease.

To determine whether results of the aminopyrine breath test, an indirect measurement of functional hepatic microsomal mass, can be correlated with mortality and changes in clinical status and liver function, 51 hospitalized patients who had alcoholic hepatitis were studied prospectively for 3 wk. The aminopyrine breath test was performed weekly, and the results were compared with clinical features of liver disease and SGOT, SGPT, bilirubin, albumin, and prothrombin time. Only an aminopyrine breath test of > 1% of administered dose of 14C as 14CO2 correlated with 3-week survival (P = 0.0075). Only an increase of more than 100% in the aminopyrine breath test was associated with clinical improvement (P = 0.0036). For the 21 patients who had histologic confirmation of alcoholic liver disease, the aminopyrine breath test also correlated best with the degree of histologic severity. In this group of patients with alcoholic hepatitis the aminopyrine breath test predicted short-term survival, clinical improvement, and histologic severity more reliably than conventional liver function tests.

Adult↗
PubMed1979

Choleresis and cholestasis produced by infusion of taurocholic acid or taurodehydrocholic acid combined with BSP in the rhesus monkey.

To study the determinants of BSP Tm in rhesus monkeys, animals with indwelling silastic catheters were infused with sufficient BSP to produce a rising plasma concentration and normal saline or taurocholic acid 3.5 mumol/min, 7.0 mumol/min, or 10.5 mumol/min. BSP Tm was 3.84 +/- 0.11 mg/kg/10 min during normal saline infusion, 5.52 +/- 0.53 mg/kg/10 min during taurocholic acid 3.5 mumol/min, despite greater bile flow with the latter compound. Higher infusion rates of taurocholic acid inhibited BSP Tm and the proportion of conjugated BSP secreted into bile, as well as bile flow and bile acid secretion. Taurodehydrocholic acid 7.0 mumol/min produced similar but less marked effects. These results indicate that bile flow does not explain the effects of bile acids on BSP Tm and suggests that bile acids exert varying effects on BSP transport or binding in micelles. The cholestasis observed with combined BSP and higher bile acid infusion rates is probably due to inhibition of liver cell intermediary metabolism or to liver cell toxicity.

Animals↗
PubMed1979

Nonalcoholic liver disease. Overlooked causes of liver injury in patients with heavy alcohol consumption.

Alcoholic subjects with abnormal liver chemistry studies are often assumed to have alcoholic liver disease, even though the diagnosis is not established by liver biopsy. To determine the magnitude of nonalcoholic liver disease in patients with heavy alcohol consumption, the data on 145 consecutive patients judged to consume at least 80 g of alcohol daily for prolonged periods, and who underwent liver biopsy at the University of Chicago, were reviewed. Nonalcoholic liver disease was suspected clinically and confirmed by liver biopsy in 40 (28 per cent), whereas alcoholic liver disease was suspected in 105 but confirmed in only 83 (80 per cent). The remaining 22 patients had liver disorders, including cholangitis or pericholangitis, acute hepatitis or some form of chronic hepatitis, for which they required appropriate therapy. Neither clinical features, hepatitis B surface antigen (HBsAg), anti-HBsAg nor serum glutamic oxaloacetic transaminase to serum glutamic pyruvic transaminase (SGOT:SGPT) ratios distinguished these 22 patients from those with alcoholic liver disease. Thus, liver biopsy is necessary for the identification of nonalcoholic liver disease in patients suspected of harboring alcoholic liver disease, since other clinical features do not allow identification of these patients.

Acute Disease↗
PubMed1979

Sodium taurocholate modifies the bile acid-independent fraction of canalicular bile flow in the rhesus monkey.

Bile acid-independent secretion and the choleretic response to taurocholate were determined in rhesus monkeys fitted with indwelling silastic cannulas in the common bile ducts. Bile acids were infused intravenously in random order at 3.5, 7.0, or 10.5 mumol/min for 1.5 h each. When data were analyzed with a single regression line, bile flow increased in proportion to the level of bile acid secretion, although the y-intercepts (the conventional measurement of bile acid-independent secretion) varied widely (77.9+/-40.9 ml/24 h). The variation in y-intercepts was observed between animals and with repeated studies in the same animal and could not be explained by sex differences or the effects of the indwelling silastic cannulas, but seemed to be related to the order of bile acid infusion. With only two taurocholic acid infusion rates (7.0 and 3.5 mumol/min), [(14)C]erythritol clearance was greater per mole of secreted bile acid when the initial bile acid infusion was at the high level, but approached zero at low bile acid secretion rates, which suggests that so-called bile acid-independent canalicular flow is closely related to bile acid secretion or is small in size. The augmentation in [(14)C]erythritol clearance when the high infusion rate was given first was also associated with an increase in biliary clearance of [(3)H]inulin, which indicates that the premeability to inulin was also enhanced. Identical experiments which substituted equimolar infusions of a nonmicelle-forming bile acid (taurodehydrocholate) for taurocholate failed to demonstrate any difference in choleretic response or biliary clearance of [(3)H]inulin with the order of bile acid infusion. These experiments demonstrate that a micelleforming bile acid, taurocholate, can increase the permeability of the biliary system to large molecular weight solutes and simultaneously modify the y-intercept and the volume of bile secreted in response to the transported bile acid. Taurocholate may, therefore, modify its own choleretic response, perhaps by altering the structure or function of bile secretory membranes, and appears to be a major determinant of so-called bile acid-independent flow in rhesus monkeys.

Animals↗
PubMed1979

Liver failure with steatonecrosis after jejunoileal bypass: recovery with parenteral nutriton and reanastomosis.

Two women, aged 41 and 51 years, developed jaundice, encephalopathy, and hypoprothrombinemia during rapid weight loss four and 12 months after jejunoileal bypass for refractory obesity. Both were treated for liver failure and received a prolonged course of nutrition parenterally and orally. Serial liver biopsy specimens demonstrated extensive alcoholic-like hepatitis and cirrhosis that improved with nutritional repletion and reanastomosis. Postoperative biopsy specimens later demonstrated minimal portal fibrosis in one patient and inactive mild cirrhosis in the other. Although previous reports indicate that patients usually die when they develop liver failure of this severity after jejunoileal bypass, prolonged intensive nutritional repletion was associated with sufficient clinical and histologic improvement in these two patients so that intestinal reanastomosis could be performed safely.

Adult↗
PubMed1978

Alkaline phosphatase activity in lymph and serum of bile duct-ligated rats.

To determine whether liver alkaline phosphatase (AP) reaches the circulation by crossing the space of Dissé and traversing lymphatic channels to the thoracic duct, AP was measured in lymph and serum hourly for 12 h after bile duct ligation in thoracic duct cannulated rats. AP did not rise at any time point in lymph, was markedly increased in serum by 7 h when compared with controls (p less than 0.05), and continued to rise for the next 5 h. However, AP in the thoracic duct lymph was increased 5-fold by corn oil feeding. Molecular weight for serum AP from bile duct-ligated rats was determined by gel chromatography and found to be approximately 125,000. Thus, hepatic AP molecules probably pass freely through the large openings in the sinusoidal endothelial lining and are transported out of the liver chiefly in sinusoidal blood, which flows more rapidly than liver lymph.

Alkaline Phosphatase↗