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Biomedical subjects

P M Hall

Publications and source records attributed to P M Hall.

17 recordsLinked to original sources
PubMed1992

Metabolism of food-derived heterocyclic amines in human and rabbit tissues by P4503A proteins in the presence of flavonoids.

The ability of human and rabbit gastrointestinal-tract microsomes to metabolize the heterocyclic amine 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) to a mutagen was determined with the Ames test. When human jejunal and ileal microsomes were used as the metabolic activation source, MeIQ produced 1675 and 388 revertants/mg of microsomal protein, respectively, and this increased to 29,230 and 17,963 revertants/mg of microsomal protein, respectively, in the presence of 100 microM alpha-naphthoflavone. MeIQ in the presence of control rabbit duodenal, jejunal, and ileal microsomes produced 2304 +/- 1018, 988 +/- 386, and 444 +/- 134 (mean +/- SD, four samples) revertants/mg of microsomal protein, respectively. In the presence of alpha-naphthoflavone (100 microM), these activities increased greater than 7-fold. P4503A proteins were detectable on Western blots of microsomes prepared from both human and rabbit small intestine. Further, rifampicin-induced rabbit hepatic-microsomal activation of MeIQ was completely inhibited at low concentrations of alpha-naphthoflavone, but at higher concentrations (i.e., 100 microM) this returned to control levels. Flavone also caused a marked stimulation of MeIQ activation in human and rabbit gastrointestinal-tract microsomes. The aforementioned data suggest that flavonoids markedly increase the ability of P4503A isozymes to activate heterocyclic amines to mutagens in the Ames test.

Animals↗
PubMed1992

Glutathione depletion enhances subanesthetic halothane hepatotoxicity in guinea pigs.

Reduced glutathione has a potential role in protecting the liver against the reactive acyl acid chloride intermediate generated during the oxidative biotransformation of halothane. Glutathione is also important in maintaining the integrity of an injured cell. Thus, the effect of decreased hepatic glutathione concentrations on covalent binding of halothane metabolic intermediates to hepatic protein and lipid and the resultant hepatic injury were investigated in male, outbred Hartley guinea pigs. The animals were injected with either 1.6 g.kg-1 dl-buthionine-S,R-sulfoximine to deplete hepatic glutathione or vehicle-control solution 24 h before exposure to 0.1% (subanesthetic) halothane for 4 h (fractional inspired oxygen tension = 0.40). Buthionine sulfoximine pretreatment depleted liver glutathione concentrations by 85% at the time of halothane exposure, without affecting the degree of halothane biotransformation or causing hepatic injury. Glutathione depletion caused a significant increase in the level of organic fluorine covalently bound to hepatic protein but not lipid after halothane exposure. Glutathione-depleted animals also exhibited a significant enhancement of hepatotoxicity after halothane exposure; plasma isocitrate dehydrogenase activity was 25-fold greater than the increase observed 48 h after exposure in animals treated with vehicle plus halothane, and the incidence and severity of hepatic injury were significantly greater, as observed by light microscopic examination of tissue 96 h after exposure. These findings are in agreement with a previously proposed mechanism of halothane-associated hepatotoxicity in guinea pigs and indicate that hepatic glutathione status may play an important role in the susceptibility of patients to halothane-induced liver injury.

Animals↗
PubMed1992

Rapid resolution of duck hepatitis B virus infections occurs after massive hepatocellular involvement.

A study was carried out to determine some of the factors that might distinguish transient from chronic hepadnavirus infection. First, to better characterize chronic infection, Pekin ducks, congenitally infected with the duck hepatitis B virus (DHBV), were used to assess age-dependent variations in viremia, percentage of DHBV-infected hepatocytes, and average levels of DNA replication intermediates in the cytoplasm and of covalently closed circular DNA in the nuclei of infected hepatocytes. Levels of viremia and viral DNA were found to peak at about the time of hatching but persisted at relatively constant levels in chronically infected birds up to 2 years of age. The percentage of infected hepatocytes was also constant, with DHBV replication in virtually 100% of hepatocytes in all birds. Next, we found that adolescent ducks inoculated intravenously with a large dose of DHBV also developed massive infection of hepatocytes with an early but low-level viremia, followed by rapid development of a neutralizing antibody response. No obvious quantitative or qualitative differences between transiently and chronically infected liver tissue were detected in the intracellular markers of viral replication examined. However, in the adolescent duck experiment, DHBV infection was rapidly cleared from the liver even when up to 80% of hepatocytes were initially infected. In all of these ducks, clearance of infection was accompanied by only a mild hepatitis, with no evidence that massive cell death contributed to the clearance. This finding suggested that mechanisms in addition to immune-mediated destruction of hepatocytes might make major contributions to clearance of infections, including physiological turnover of hepatocytes in the presence of a neutralizing antibody response and/or spontaneous loss of the capacity of hepatocytes to support virus replication.

Age Factors↗
PubMed1991

Assessing the progression of renal disease in clinical studies: effects of duration of follow-up and regression to the mean. Modification of Diet in Renal Disease (MDRD) Study Group.

Many clinical studies of the effects of low-protein and low-phosphorus diets on the course of chronic renal disease have used the rate of decline in renal function to assess the rate of progression. In this report, data from the feasibility phase of the Modification of Diet in Renal Disease Study were used to analyze methods used in other studies. The focus is particularly on the effects of duration of follow-up and of regression to the mean. The findings are summarized as follows. (1) During the mean follow-up period of 14.1 months, rates of decline in glomerular filtration rate, creatinine clearance, and the reciprocal of the serum creatinine concentration were highly variable among individuals, and mean rates of decline were slow. (2) Precision of estimates of individual rates of decline in renal function were relatively low and improved with increasing duration of follow-up. (3) Correlations between rates of decline in creatinine clearance and the reciprocal of the serum creatinine concentration with glomerular filtration rate in individuals were significant but weak and became stronger with increasing duration of follow-up. (4) After entry into the study, mean rate of decline in the reciprocal of the serum creatinine concentration became less negative. The change predicted simply from regression to the mean was 68.4% of the observed change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Isoniazid potentiation of a guinea pig model of halothane-associated hepatotoxicity.

Isoniazid (INH) is a selective inducer of cytochrome P-450 isozymes that are involved in the biotransformation of organohalogen anesthetics. It has been used to produce a rat model of halothane-associated hepatotoxicity that was linked to enhanced oxidative biotransformation of the anesthetic. Guinea pigs were pretreated with INH in order to potentiate halothane-induced hepatic necrosis and to study the oxidative pathway as a hepatotoxic mechanism in this species. The animals received either 12.5, 25.0 or 50.0 mg kg-1 INH i.p. for 7 days. Following halothane exposure, there were dose-dependent increases in plasma levels of the oxidative halothane metabolite, trifluoroacetic acid. These increases were associated with increases in 48 h plasma alanine aminotransferase (ALT) levels. When combined with halothane exposure, the two higher doses of INH killed the animals before planned termination. These deaths were not attributable to hepatic failure. Dividing the 25 mg kg-1 INH dose into twice daily injections of 12.5 mg kg-1 reduced deaths. INH pretreatment control animals exhibited occasional non-dose-dependent increases in ALT as well as the occurrence of fatty vacuolization of hepatocytes at the highest dose. Even though INH pretreatment enhanced oxidative halothane biotransformation and subsequent hepatotoxicity, sensitivity of guinea pigs to the deleterious actions of INH would contraindicate its use as a cytochrome P-450 induction agent.

Alanine Transaminase↗
PubMed1990

Influence of enzyme induction and exposure profile on liver injury due to chlorinated hydrocarbon inhalation.

Rats were exposed for four weeks either to air or to vapours of chloroform, carbon tetrachloride or 1,1-dichloroethylene given either as a constant concentration (continuous profile) or as repeated exposures for 6 hr per day, 5 days per week (fluctuating profile). Vapour concentrations were used such that the total exposure (concentration x time) was the same for the two profiles. Within each group, some animals received the enzyme-inducing agents, phenobarbitone or 1,3-butanediol, in their drinking water. Separate experiments were conducted to determine the influence of enzyme inducers and vapour concentration on chlorocarbon uptake and metabolism. In the case of chloroform, hepatic injury was more severe in animals exposed to constant vapour concentration, while dichloroethylene was more toxic when given as a fluctuating profile, especially in butanediol-treated rats. Carbon tetrachloride hepatotoxicity was similar in the two exposure profiles but was exacerbated by butanediol treatment. Butanediol-treated animals in the fluctuating profile group showed evidence of developing cirrhosis. These results could not be fully explained on the basis of the effect of enzyme inducers and exposure profile on amount of agent metabolized. Both the amount of toxic metabolites and the temporal pattern of their formation appear to be important determinants of liver injury.

Administration, Inhalation↗
PubMed1990

Hypertension in women.

Hypertension is a common disorder which affects over 40 million individuals in the United States alone. Systemic (idiopathic) hypertension is particularly prevalent in elderly women who seem to tolerate this affliction better than their male counterparts. Women with hypertension should be cautioned about the effects of estrogen-containing oral contraceptives which may cause a further elevation in systemic blood pressure. However, postmenopausal estrogen supplementation does not produce adverse effects on blood pressure and, in fact, may offer cardiovascular protection. Renovascular hypertension, particularly as a result of fibromuscular hyperplasia, is more prevalent in women than men. For women, as for men, tobacco abuse and advanced age are associated with an increased prevalence of atherosclerotic renal artery stenosis.

Contraceptives, Oral, Hormonal↗
PubMed1979

Chronic glomerular microangiopathy and metastatic carcinoma.

Two patients with metastatic colonic adenocarcinoma developed deterioration of renal function six and nine months after the diagnosis of malignant disease. A renal biopsy specimen in one case and both postmortem specimens revealed thickening of glomerular capillary loops with focal reduplication of basement membrane-like material. Ultrastructural examination of all three specimens demonstrated a lucent subendothelial zone and no evidence of electron dense deposits. Antifibrinogen staining outlined most capillary loops in one case. It appears that chronic intravascular coagulation induced by the neoplasm was the major pathogenetic process involved in the production of the glomerular lesion in each case.

Adenocarcinoma↗
PubMed1976

Pharmacokinetics of amikacin in patients with impaired renal function.

Pharmacokinetic parameters were determined after a single intramuscular injection of 7.5 mg of amikacin/kg to 10 volunteers with impaired renal function (creatinine clearance rate, 2.2-65ml/min per 1.73 m2) and to six volunteers with normal renal function. The mean peak concentrations of amikacin in sera of the two groups did not differ significantly from each other and exceeded by two to five times the reported in vitro minimal inhibitory concentrations for the majority of Pseudomonas aeruginosa and Enterobacteriaceae strains. There was a significant linear relation between the elimination rate constant of amikacin and the rate of creatinine clearance; there was a significant nonlinear relation between the half-life of amikacin and the serum creatinine concentration. Knowledge of these relations may aid in adjustment of the dosage of amikacin in patients with impaired renal function, especially when such information is used in conjunction with serum assays of amikacin.

Adolescent↗
PubMed1976

Laboratory tests of renal function.

There are several tests available to evaluate renal function. Because the kidney has such complex and varied functions, no one test can adequately measure them. A rough measure of renal function can be obtained by examining the constituents of the urine. More specific aspects of tubular and glomerular function require more complex tests. Proper interpretation of these tests, however, requires knowledge of the patient's status and clinical course.

Acidosis, Renal Tubular↗
PubMed1976

Revascularization of the kidney after occlusion of the aorta and both renal arteries.

A patient who developed acute renal artery thrombosis as a complication of distal abdominal aortic occlusion is described. Because of the presence of an extensive collateral arterial supply, the right kidney survived and revascularization was accomplished successfully with a saphenous vein graft interposed between the superior mesenteric and the right renal arteries. Criteria for revascularization of renal artery occlusion are presented, with emphasis on the importance of collateral circulation and the elective correction of distal aortic thrombosis.

Aortic Diseases↗
PubMedDate not supplied

Acute tubulointerstitial nephritis.

Between 1980 and 1988, 12 patients at the Cleveland Clinic had biopsy-proven acute tubulointerstitial nephritis. Etiologies of the disease included drugs, systemic illness, and idiopathic causes. Clinical features were nonspecific, and the diagnosis of acute tubulointerstitial nephritis was seldom entertained in these patients prior to biopsy. Seven patients had unrelated underlying renal disease. Treatment included discontinuation of the offending agent and/or a trial of steroids. All patients had final creatinine levels lower than at diagnosis. Because the condition is potentially reversible, this disease should be considered in all patients with new azotemia who do not exhibit prerenal factors, features typical of acute tubular necrosis, red blood cell casts heralding a glomerular process, or evidence of obstructive uropathy.

Acute Disease↗