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Biomedical subjects

B A Chapman

Publications and source records attributed to B A Chapman.

At least 19 recordsLinked to original sources

Viral hepatitis in the Christchurch community.

AIM: To determine the relative frequency of known causes of viral hepatitis in the Christchurch community. METHODS: Serum samples were collected at a private laboratory from patients aged 15-75 years who had an elevated transaminase of at least twice normal. RESULTS: One hundred and thirty-three subjects entered the study of whom 32 were positive for Epstein Barr virus, three for cytomegalovirus, nine for hepatitis A virus, and eight for hepatitis B virus. Paired convalescent samples were obtained from 64 of the remaining 81 subjects (17 lost or declined) and seven of these were positive for hepatitis C. Assuming a similar percentage in the lost/declined group this corrects to nine. CONCLUSION: The relative frequency of viral agents causing hepatitis was Epstein Barr virus 52%, cytomegalovirus 5%, hepatitis A virus 15%, hepatitis B virus 13% and hepatitis C virus 15%. Hepatitis C virus is a common cause of viral hepatitis in the Christchurch community.

Adolescent

The prevalence of antibodies to hepatitis C virus in patients with chronic liver disease.

OBJECT: to determine the prevalence of antibodies to hepatitis C virus in selected groups of patients with chronic liver disease. METHODS: serum specimens were obtained from 39 patients with chronic liver function abnormalities of uncertain cause (group A), from 15 patients with autoimmune chronic active hepatitis (group B) and from 10 patients with chronic hepatitis B (group C). In an extension of the study, serum was collected from sexual partners of patients found to be HCV seropositive. A second generation ELISA assay (Abbott) was used to analyse the specimens. RESULTS: ten patients (26%) in group A were seropositive, one (7%) in group B and three (30%) in group C. Risk factors for infection included blood transfusion in three, intravenous drug use in six (including the only positive patient in group B) and both factors in another patient. Only one of the 10 sexual partners tested was positive but this subject was also an intravenous drug user. CONCLUSIONS: hepatitis C virus is a significant cause of chronic liver disease in Christchurch. Important risk factors include blood transfusion and intravenous drug use although sporadic cases occur. Transmission to sexual partners is uncommon. The second generation assay does not appear to give false positive results in autoimmune chronic active hepatitis.

Adult

Pyogenic liver abscesses: a retrospective review of 24 cases.

OBJECTS: to review our experience of pyogenic liver abscess with attention to the value of ultrasound and computerised tomography, and the duration of antimicrobial therapy. METHOD: retrospective review of all pyogenic liver abscesses in Christchurch hospitals between 1972 and 1989. RESULTS: twenty-four cases were identified. The presentation of these cases was typical of those described in other series. Ultrasound scanning was positive in 69% of cases, and computerised tomography in 94%. Enteric organisms were isolated from blood or abscess cavities in all but two cases. Two patients died soon after admission and three were treated with antimicrobial therapy alone. The remainder underwent either a percutaneous or surgical drainage procedure, and received antimicrobial therapy. The antimicrobial therapy was clearly inappropriate in two patients. Eight patients (67%) with single abscesses received less than 10 days of antimicrobial therapy. Four patients (50%) with multiple abscesses received less than 18 days therapy. No patient relapsed. CONCLUSIONS: ultrasound is a convenient initial imaging technique, but may give false negative results. Computerised tomography should be done promptly if clinical suspicion of a liver abscess persists. Both surgical and percutaneous drainage techniques gave good results in combination with antimicrobial therapy. It is probably unnecessary to give prolonged courses of antimicrobial therapy following drainage of single liver abscess, provided there is rapid resolution. Multiple abscesses, or those which are not drained, may require longer courses of antimicrobial therapy.

Adolescent

Apolipoprotein localization in the human bile duct and gallbladder.

Apolipoproteins AI, AII and B were identified in the normal and pathological human bile duct and the gallbladder epithelium using an avidin-biotin immunoperoxidase technique. Small intestine and stomach sections served as positive and negative controls respectively. Staining was focal for apolipoproteins AI and AII, and continuous for apolipoprotein B. In addition to homogenous and granular cytoplasmic staining, foamy cytoplasmic staining, particularly for apolipoproteins AI and AII, was observed around lipid droplets in cells containing much lipid. No correlation between a particular pathological condition of the gallbladder (acute cholecystitis, mucocele, chronic cholecystitis, cholesterolosis) and staining pattern or intensity of staining was found for any of the apolipoproteins, although both apolipoproteins AI and AII stained more intensely than apolipoprotein B in each group. Positive staining was also found for all apolipoproteins in epithelial cells which had invaded the underlying connective tissue (gallbladder carcinoma), suggesting that the epithelial cells are capable of synthesizing apolipoproteins de novo. In this latter case, apolipoprotein B stained more intensely than for either AI or AII, and significantly (p less than 0.05) more strongly than that found in the other pathological groups. The identification of apolipoproteins in the gallbladder epithelium raises the interesting question of their origin and functional role.

Apolipoproteins

The effect of ethanol on phospholipid metabolism in rat pancreas.

The phospholipid effect involves agonist-induced breakdown of phosphatidyl inositol (or polyinositides) generating second messengers followed by increased incorporation of 32P during the resynthetic phase of the cycle. Ethanol, an aetiological factor in pancreatitis, has been shown to have various effects on pancreatic secretion. In this study ethanol decreased the incorporation of 32P into phosphatidyl inositol but had no effect on the stimulated breakdown of prelabelled phosphatidyl inositol. However, in addition to recycling of phosphatidyl inositol stimulation of pancreatic tissue results in increased incorporation of precursors into other phospholipids. Cholecystokinin increased the incorporation of both [U-14C] glucose and 32P into phosphatidyl ethanolamine 3-fold but had no effect on 32P incorporation into phosphatidyl choline. As well as increased incorporation of 32P into phosphatidyl inositol (8-fold) cholecystokinin also increased the incorporation of [U-14C] glucose into phosphatidyl inositol (4-5-fold) implying significant de novo synthesis of 1,2 diacyl glycerol in addition to the currently accepted recycling of the 1,2 diacyl glycerol back to phosphatidyl inositol. Ethanol caused an inhibition of 32P incorporation into total phospholipid of rat pancreas during basal and stimulated conditions. When individual phospholipids were separated ethanol was found to decrease the incorporation of 32P into phosphatidyl choline under basal conditions and into all phospholipids during cholecystokinin stimulation. With [U-14C] glucose as the precursor, ethanol inhibited its incorporation into phosphatidyl choline only. Ethanol did not alter the total 32P radioactivity in the aqueous phase of the pancreatic extract nor the percent incorporated into nucleotides. This excluded decreased uptake of 32P and incorporation into nucleotides as a mechanism for the differential inhibition of 32P versus [U-14C] glucose incorporation into phospholipids other than phosphatidyl choline under stimulated conditions.

Animals

The effect of ethanol on enzyme synthesis and secretion in isolated rat pancreatic lobules.

This study investigates the effect of ethanol on enzyme synthesis and secretion in rat pancreatic lobules. Ethanol caused a dose-dependent inhibition of 3H-leucine incorporation into total protein. Examination of the time dependence showed that ethanol inhibited protein synthesis at each time point. Removal of ethanol partially reversed this inhibition. An autoradiograph of the newly synthesized proteins separated on SDS-PAGE showed that ethanol inhibited synthesis of all proteins. 14C-cycloleucine uptake was not altered by ethanol, excluding inhibition of amino acid uptake as the mechanism for the decreased protein synthesis induced by ethanol. Electron microscopy revealed no ultrastructural damage. Ethanol had no effect on the stimulated release of (i) amylase from zymogen granules nor (ii) newly synthesized pulse labelled enzymes. Acetaldehyde had no inhibitory effect on enzyme synthesis or secretion indicating that ethanol per se and not its metabolite is inhibitory. The decreased synthesis after acute exposure to ethanol with preservation of exocytosis would limit the autodigestive potential of pancreatic tissue. This may explain why isolated toxic doses of ethanol are rarely if ever associated with pancreatitis.

Acetaldehyde

Dientamoeba fragilis: a bowel pathogen?

Although many patients infected with Dientamoeba fragilis suffer gastrointestinal symptoms, controversy still surrounds the pathogenic role of this intestinal protozoan. We describe three patients infected with D fragilis who had gastrointestinal symptoms. In the first patient symptoms resolved with therapy before the protozoan was eradicated from the stool, however in the second, symptoms persisted unabated despite clearing of the organism. In the third patient, symptoms resolution was associated with effective treatment. We discuss the life cycle, diagnosis and treatment of this organism and its role as a pathogen.

Adult

Inhibition of biliary phospholipid and cholesterol secretion by cefoperazone.

The effect of cefoperazone, a third-generation cephalosporin, on biliary lipid secretion in rats was examined. Rats were anesthetized with ether and the mid-lumbar vein and common bile duct cannulated. Bile acid secretion was maintained by intravenous taurocholic acid infusion (28 mumol/hr). A 1-hr control period was followed by intravenous cefoperazone infusion at either submaximal (20 mumol/hr), or supramaximal (60 mumol/hr) concentrations. At the cefoperazone infusion rate of 20 mumol/hr (biliary secretion of 7.1 +/- 1.6 mumol/hr) phospholipid secretion fell 19% and cholesterol secretion fell 31%; at a cefoperazone infusion rate of 60 mumol/hr (biliary secretion rate of 27.1 +/- 5.1 mumol/hr) phospholipid and cholesterol secretion were further reduced 40% and 56%, respectively, of controls. All changes were significant (P less than 0.01). Inhibition of both cholesterol and phospholipid secretion paralleled each other, was dose-dependent, and reversible. Cefoperazone's inhibitory action was abolished at a bile acid infusion rate of 108 mumol/hr. Cefoperazone was not found to be associated with bile acid micelles or mixed micelles as determined by ultracentrifugation and gel filtration. Thus, the effect of cefoperazone on biliary lipid secretion is not due to the impairment of mixed micelle formation in the canalicular lumen but rather its inhibitory effect appears to be due to a presecretory event.

Animals

The incorporation of [myo-2-3H] inositol into phosphatidyl inositol of stimulated rat pancreas.

The 'phospholipid effect' involves agonist induced breakdown of phosphatidyl inositol (PI) or its phosphorylated derivates with increased incorporation of 32P or [myo-2-3H] inositol during resynthesis. In rat pancreas pancreozymin and bethanecol resulted in the standard dose dependent increased incorporation of 32P into PI which was paralleled by increased amylase secretion. By contrast the incorporation of [myo-2-3H] inositol into PI was significantly decreased by pancreozymin whereas bethanecol had no effect. However, pancreozymin caused a 30% decrease in labelled PI irrespective of whether it was prelabelled with 32P or [myo-2-3H] inositol. Thus in rat pancreas, pancreozymin resulted in the standard agonist induced breakdown of pre-labelled PI but inhibited the incorporation [2-3H-myo] inositol during the resynthetic phase.

Amylases

Biliary secretion of cefoperazone and its inter-relationship with bile acid transport in the rat.

Cefoperazone is a third generation cephalosporin which is secreted predominantly in bile. This study set out to examine the effect of stimulating bile choleresis on the biliary secretion of cefoperazone. Stimulation of both bile acid-dependent and independent bile flow (phenobarbitone pretreatment) hastened the peak appearance of a pulse of cefoperazone into bile. Although the biliary secretion rate of cefoperazone was enhanced by bile acid infusion, the % recovery and maximal biliary concentration were reduced. The reciprocal effect of continuous cefoperazone infusion on the rate of biliary transport of a pulse of bile acid was examined. Cefoperazone infusion hastened the biliary transport of glycocholate. Net recovery of glycocholate was unaffected.

Animals

Colonoscopy and bacteraemia: an experience in 50 patients.

There is little consensus concerning the incidence of bacteraemia during colonoscopy and the need for antibiotic prophylaxis in susceptible patients. Hepatic abscesses in one patient which may have been related to prior colonoscopic examinations led the authors to carry out a prospective study of 50 patients undergoing colonoscopy. Multiple blood cultures were carried out to maximise the positive yield of transient bacteraemia and to attempt to determine the time when bacteraemia is most likely to occur. Five patients had positive blood cultures. In two patients S epidermidis was isolated, but only from the precolonoscopic blood sample. In three subjects enteric organisms were cultured from blood samples obtained during the procedure. In one of these three the same organism was cultured from the preendoscopic blood sample so that in only two patients (4%) could the bacteraemia be attributed to the colonoscopy. These results would suggest that the risk of bacteraemia during colonoscopy is low.

Adult

Distribution of biliary cholesterol between mixed micelles and nonmicelles in relation to fasting and feeding in humans.

To further investigate the nonmicelle mode of cholesterol transport in human bile, we examined its levels in relation to fasting and feeding. T-tube bile samples were collected (for 30 min) every 4 h over a 24-h period. All patients (3 with cholesterol gallstones; 1 with pigment stone) had their T tube clamped for a minimum of 4 days before the study to allow the bile acid pool to replete. Biliary lipid concentrations in all patients increased with feeding and decreased with fasting. However, because of a greater decrease in bile acid concentration relative to cholesterol concentration during the fasting period, fasting bile was consistently more saturated than bile obtained while feeding. Associated with the increase in lithogenic index with fasting was a decrease in the micelle solubilized cholesterol and an increase in nonmicelle solubilized cholesterol. At low bile acid concentrations (fasting) most biliary cholesterol is therefore transported as a nonmicelle complex, whereas at high bile acid concentrations (feeding) most of the cholesterol is transported in the mixed micelle. No nucleation of the biliary samples was observed in any of the patients over a 10-day period of observation. Thus the biliary nonmicelle complex (presumably vesicles) has a major cholesterol transport function especially at low bile acid concentrations.

Adult

Halothane hepatitis: toxicity or hypersensitivity?

A 32 year old female developed a severe hepatitis (serum bilirubin 544 mumol/l) one week after a halothane anaesthetic. Six months later a general anaesthetic was administered via a halothane free circuit without incident. A year later a further non halothane anaesthetic was administered this time utilising the routine circuit after briefly flushing the rubber tubing with oxygen. That evening she became febrile and the following day abnormal liver function tests were documented. She remained asymptomatic.

Adult

Lithocholate detoxification and biliary secretion in the rat.

To define the efficiency of hepatic detoxification, 14C lithocholate in combination with taurocholate was continuously infused intravenously into rats until steady-state. Quantitation of hepatic radiolabelled bile acid under these conditions showed only 11% of total liver bile acid was unmetabolised, indicating very efficient detoxification of lithocholate, in its most hepatotoxic state. Interestingly we found the rate for each bile acid to reach steady-state differed. To test whether the difference was due to glutathione S-transferase binding, as proposed by Strange et al (8), glutathione S-transferase levels were induced by phenobarbitone treatment. An increase in cytosol glutathione S-transferase levels had no effect on the time it took for each bile acid to reach steady-state.

Animals

Increased phospholipid synthesis in the stimulated rat and human pancreas.

Stimulation of the exocrine pancreas is associated with marked changes in pancreatic phospholipid metabolism. It has been previously established that de novo synthesis of phospholipids constitutes part of this "phospholipid effect". This study has demonstrated that in vitro stimulation of the rat pancreas utilising bethanecol and pancreozymin results in increased incorporation of labelled glucose into phosphatidyl inositol and, to a lesser extent, other phospholipids, suggesting increased de novo synthesis of these compounds. However, secretin which is believed to act via a different intracellular pathway, did not exert such an effect. The relevance of this animal model is indicated by the demonstration of increased incorporation of labelled glucose into phospholipids of human pancreas stimulated in vitro by bethanecol or sincalide (the active carboxy terminal octapeptide of pancreozymin).

Animals

The management of ascites using the Rhodiascit Apparatus ("Paris Pump").

The Rhodiascit Apparatus ("Paris Pump") which ultrafilters sodium and water from ascitic fluid allowing reinfusion of a protein-rich concentrate, has been found to be a valuable procedure in the management of ascites associated with liver cirrhosis. The device was evaluated in eight patients with the aim of rapidly controlling ascites with minimum hospitalisation. The duration of the procedure varied from 8.5 to 55 hr (mean 27 hr) and resulted in a mean girth reduction of 13 cm (range 5.7 to 24 cm) and a mean weight loss of 13.6 kg (range 5.7 to 23 kg). Serum electrolytes and total protein were unchanged; a slight but insignificant rise in serum creatinine was observed. Three infective episodes occurred, but these were easily controlled. The procedure was, in general, well tolerated, inexpensive and allowed rapid relief of ascites with few complications.

Adult