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Biomedical subjects

A L Baker

Publications and source records attributed to A L Baker.

116 records · Page 7Linked to original sources
PubMedDate not supplied

Intestinal calcium absorption and vitamin D status in chronic cholestatic liver disease.

Metabolic bone disease is common in patients with cholestatic liver disease. The importance of vitamin D status and calcium malabsorption in the pathogenesis of bone disease in these patients remains undefined. We have measured intestinal calcium absorption in relation to vitamin D status in 14 patients with chronic cholestatic liver disease including 11 with primary biliary cirrhosis. Fractional calcium absorption was determined from radioactive counts in the right forearm after separate oral and intravenous doses of 47CaCl2 in the fasting state. Eight of 14 patients (57%) had a decreased calcium absorption compared to controls. A significant correlation was observed between serum 25-hydroxyvitamin D levels and fractional calcium absorption (r = 0.623, p less than 0.02). Treatment with oral 25-hydroxyvitamin D3 in three patients with low serum 25-hydroxyvitamin D levels resulted in correction of serum 25-hydroxyvitamin D levels and improvement in fractional calcium absorption. No correlation was found between serum 1,25-dihydroxyvitamin D levels and fractional calcium absorption (r = 0.221). Calcium malabsorption was common in this series of patients, and serum 25-hydroxyvitamin D levels were useful in predicting fractional calcium absorption. Treatment with oral 25-hydroxyvitamin D3 was accompanied by improved calcium absorption.

Adult↗
PubMedDate not supplied

Pattern and prognosis of liver function test abnormalities during parenteral nutrition in inflammatory bowel disease.

The pattern of liver function test abnormalities was examined during total parenteral nutrition (TPN), using both dextrose and fat emulsions as caloric sources, in 92 patients with inflammatory bowel disease. Seventy-two patients had completely normal tests before TPN while 20 had one or more abnormal liver function tests before TPN was started. Serum bilirubin levels were normal in all patients before TPN; within 2 weeks on TPN, 25% of patients had elevated bilirubin levels. Serum alkaline phosphatase rose to values above normal in 25% of patients with normal starting values but did not change in those with abnormal baseline liver function tests. Elevations of SGPT were characteristically more pronounced than were elevation of SGOT. After 2 weeks of TPN, mean serum SGOT rose from 15 to 26 IU per liter (p less than 0.01) in patients with normal baseline values and from 28 to 50 IU per liter in those with abnormal baseline values. Elevations of serum SGPT were most common, affecting 25% of patients with normal baseline. The mean SGPT value rose from 13 to 38 IU per liter (p less than 0.01) at 1 week of TPN. In patients with abnormal tests before TPN, the mean SGPT value rose from 45 to 102 IU per liter (p less than 0.05). Liver biopsies performed in four patients with substantial elevations of aminotransferases revealed only minor nonspecific changes and no fatty infiltration. Elevated liver function tests promptly returned to baseline after TPN was discontinued, and progressive liver disease was not observed in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMedDate not supplied

Comparison of the phenacetin and aminopyrine breath tests: effect of liver disease, inducers and cobaltous chloride.

The phenacetin breath test (PBT) has been proposed as an alternative to the aminopyrine breath test (ABT) for the assessment of hepatic function. To investigate the clinical utility of the PBT, we compared the PBT with the ABT in 9 healthy subjects and 18 patients with biopsy-proven liver disease. We also investigated the effects of cytochrome P-450 inducers in humans and rats, and the effect of cobaltous chloride (CoCl2) in rats on the PBT to elucidate the relationship between the rate of phenacetin deethylation and exhaled labeled CO2 derived from phenacetin. In humans with abnormal ABTs, the PBT correlated with the ABT (r = 0.77), but in healthy humans there was no correlation between the two breath tests. Rifampin pretreatment in healthy humans induced the ABT by 27%, but did not induce the PBT. In rats the PBT was not induced by 3-methylcholanthrene pretreatment at phenacetin doses of 1 mg per kg, but was induced by both 3-methylcholanthrene (178%) and phenobarbital (142%) at 10 mg per kg phenacetin. Pretreatment of rats with CoCl2, which reduces cytochrome P-450 content, decreased the PBT by 40% and the ABT by 84%. The insensitivity of the PBT to induction except at high doses of phenacetin suggests that phenacetin deethylation is not the rate-limiting process modulating exhaled labeled CO2 in healthy subjects, and that the PBT does not generally reflect normal or induced phenacetin dealkylation rates. The PBT, however, did reflect hepatic damage and may even be better than the ABT for grading the severity of hepatic damage.

Adult↗
PubMedDate not supplied

The aminopyrine breath test does not correlate with histologic disease severity in patients with cholestasis.

To determine whether the aminopyrine breath test can be used to document the presence of cirrhosis in patients with cholestatic liver disease, 19 patients (13 primary biliary cirrhosis, 4 sclerosing cholangitis and 2 chronic extrahepatic bile duct obstruction) underwent clinical and biochemical evaluations, liver biopsies and an aminopyrine breath test. Results were compared with those in 10 patients with biopsy-proven chronic active hepatitis with bridging and/or cirrhosis and in 22 healthy subjects. The aminopyrine breath test results in the 10 cholestatic patients with cirrhosis were not significantly different from the results in precirrhotic cholestatic patients (mean +/- S.D., 11.2 +/- 5.0 vs. 11.6 +/- 2.8% dose per 2 hr, p greater than 0.05) or healthy subjects (11.5 +/- 2.9% dose per 2 hr). In contrast, the results in the patients with chronic hepatitis were markedly depressed (3.2 +/- 1.9% dose per 2 hr, p less than 0.05). The aminopyrine breath test results did not correlate with results of conventional liver function tests in the cholestatic patients. These results demonstrate that the aminopyrine breath test is not clinically useful in identifying the presence of cirrhosis in patients with cholestatic liver disease, and provide further evidence that decreased microsomal enzyme function is a late feature of cholestatic liver disease.

Adult↗
PubMedDate not supplied

Chemoimmunoconjugate development for ovarian carcinoma therapy: preclinical studies with vinca alkaloid-monoclonal antibody constructs.

Preclinical efficacy studies are presented in a human ovarian carcinoma model utilizing several novel conjugation strategies with the KS1/4 monoclonal antibody and derivatives of the vinca alkaloid desacetylvinblastine hydrazide. The chemoimmunoconjugates KS1/4-beta-alanine-methylenemalonic acid ethyl ester-4-decacetylvinblastine 23-hydrazide (KS1/4-BAMME-DAVLB-HY), KS1/4-beta-alanine-5-formylpyrrole-2-carboxylic acid-4-desacetylvinblastine 23-hydrazide (KS1/4-BAP-DAVLB-HY), and KS1/4-4-desacetylvinblastine 23-hydrazide were explored in the OVCAR-3 human ovarian carcinoma xenograft model. These conjugates, constructed with variable linker stability between the vinca alkaloid and the antibody, were studied by comparing the route of administration and the treatment schedule. Under these conditions a mean survival time from 28 to 35 days in untreated control animals was observed. Significant increases in survival (i.e. 3-9-fold over untreated control animals) were observed with all the immunoconjugates tested but with varying potency and efficacy dependent on linker strategy. Parallel therapy with equivalent doses of free DAVLB-HY or a non-antigen-binding immunoconjugate did not significantly increase the survival of the animals. These results suggest several chemoimmunoconjugate strategies for site-directed therapy of human ovarian cancer.

Adenocarcinoma↗
PubMedDate not supplied

Bacterial infection as a complication of liver transplantation: epidemiology and risk factors.

A retrospective survey was undertaken to characterize the epidemiology of bacterial infection in 79 patients who underwent 103 operations for orthotopic liver transplantation. Fifty-four patients (68%) developed 115 bacterial infections (1.46 episodes per patient), and seven patients died as a result of these infections. Fifty-three percent of bacterial infections occurred within 2 weeks after transplantation and were designated as early infections. The most common sites of infection were the abdomen (35 cases), the bloodstream (31 cases), and the surgical wound (19 cases). Aerobic enteric gram-negative bacilli were the predominant pathogens, and other pathogenic organisms were enterococci, staphylococci, and Pseudomonas bacteria. Logistic regression analysis identified prolonged duration of surgery (greater than or equal to 8 hours) and an elevated bilirubin level (greater than or equal to 12 mg/dL) as risk factors for early bacterial infection at any site; risk factors for abdominal or wound infection were prolonged duration of surgery, increased operative transfusion requirement (greater than or equal to 2 blood volumes), and prior hepatobiliary surgery. Awareness of the sites, pathogens, and time of onset of bacterial infection provides a basis for improved prophylaxis and empiric therapy.

Bacterial Infections↗