Biomedical subjects
P Kerlin
Publications and source records attributed to P Kerlin.
Universal occurrence of glomerular abnormalities in patients receiving liver transplants.
We conducted a prospective study of renal histology and function in 18 consecutive nonalcoholic patients who underwent orthotopic liver transplantation (OLT). Despite well-preserved renal function, all patients had abnormal renal biopsies. Four patterns of glomerular injury were identified: minor glomerular abnormalities (eight patients), hepatic glomerulosclerosis (seven), membranoproliferative glomerulonephritis (one), and IgA nephropathy (one). In one patient there was insufficient tissue to allow classification. There was a trend toward lower plasma bilirubin and higher plasma albumin in patients with minor glomerular abnormalities than in the group of patients with more severe forms of glomerular injury (29 v 82 mumol/L, 35.5 v 30 g/L; P = 0.1, 0.1 greater than P greater than 0.05, respectively). Glomerular changes persisted in the three patients who died within 7 weeks post-OLT. IgM immunofluorescence was present in all biopsies and IgA in 11. IgM-containing circulating immune complexes occurred in five patients, suggesting a pathogenic role for IgM immune complex deposition. The significance of cirrhosis-associated glomerular abnormalities is not yet known. They may contribute to the hepatorenal syndrome and the renal dysfunction that occurs in up to 94% of patients post-OLT.
Isolated hepatitis B core antibody--can response to hepatitis B vaccine help elucidate the cause?
The finding of a positive hepatitis B core antibody (anti-HBc) in the absence of hepatitis B surface antigen (HBsAg) or hepatitis B surface antibody (anti-HBs) is relatively uncommon. This finding is known to occur during the 'window period' of acute hepatitis B between loss of HBsAg and the appearance of anti-HBs. It may also occur with active infection or following resolution. The aim of this study was to determine if response to hepatitis B vaccination would allow the separation of these subgroups of patients with isolated anti-HBc. Seventeen patients with persistent isolated core antibody were vaccinated and serum obtained at 2, 4 and 8 weeks. Results were compared with a seronegative control group. Six subjects (35%) but no control patients (p = 0.016) responded with a titre of greater than 50mIU/mL at two weeks, suggesting an anamnestic response due to prior infection and immunity. A further seven subjects (41%) finally seroconverted (anti-HBs titre greater than 10mIU/mL) thus excluding chronic infection and suggesting initial false positive results. Only two subjects did not respond to a full course of vaccination, but neither they nor any other subjects were positive for HBV DNA. These results indicate that hepatitis B vaccination and subsequent measurement of anti-HBs will identify evidence of past infection in the form of an anamnestic response in up to one third of the patients and will also exclude chronic infection on the grounds of a normal vaccine response in a majority of the remainder.
Piroxicam induced submassive necrosis of the liver.
Several widely used non-steroidal anti-inflammatory drugs have been reported as causing severe hepatitis. Three cases of severe acute hepatitis have been reported in association with piroxicam. A fatal submassive necrosis that occurred in a 68 year old lady who had received piroxicam for 15 months is described. A 48 year old man who developed submassive hepatic necrosis six weeks after beginning piroxicam but was successfully treated with orthotopic liver transplantation is also reported. Piroxicam may induce submassive necrosis of the liver, probably as an idiosyncratic reaction.
Liver transplantation in the 1990s.
Liver transplantation is now the therapy of choice for advanced, irreversible, progressive liver disease. The authors look at who should have a transplant and explain that the predicted outcomes of surgery depend on the pre-operative disease. A brief overview of post-operative care is given.
Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis before transplantation.
Patients with primary sclerosing cholangitis are at an increased risk of developing cholangiocarcinoma, which is difficult to diagnose because the biliary tree is already distorted. Eleven patients with primary sclerosing cholangitis who underwent orthotopic liver transplantation at this hospital were evaluated. Four patients had coincidental histologically proved cholangiocarcinoma. Patients with cholangiocarcinoma in contrast to patients without tumour presented with rapid onset of persistent jaundice, pruritus, and weight loss associated with an appreciable rise in bilirubin (8x v 2x) and alkaline phosphatase (3.5x v 1.2x) over one year. Cholangiography and computed tomography showed appreciably dilated intrahepatic bile ducts (3/4 v 0/7). The diagnosis of cholangiocarcinoma could only be established before operation in one patient by fine needle aspiration cytology. Tumour was recognised at operation in one other. Histological examination of hepatectomy specimens showed that patients with cholangiocarcinoma had less advanced histological features of primary sclerosing cholangitis. Multiple areas of carcinoembryonic antigen positive epithelial atypia and carcinoma in situ were found in all patients with cholangiocarcinoma. Cholangiocarcinoma recurred in two patients at 14 and 39 months after transplantation. Superimposed cholangiocarcinoma can be predicted in most patients with cholangitis before transplantation, although a definitive diagnosis is difficult to make. Their prognosis after successful transplantation is guarded.
Only patients with dysplasia progress to adenocarcinoma in Barrett's oesophagus.
Columnar lined oesophagus (Barrett's oesophagus) carries a risk for the development of adenocarcinoma. Epithelial dysplasia appears to be a precursor but the utility of this marker for predicting subsequent adenocarcinoma is unsettled. We therefore prospectively studied 81 patients with histologically proven columnar epithelium of at least the distal 3 cm of the tubular oesophagus with regular endoscopic biopsies for a total of 289.2 patient years (mean 3.6 years, range 0.5-8). Twenty three patients (28%) had epithelial dysplasia detected during follow up. Both patients with persistent high grade dysplasia present on initial biopsies developed adenocarcinoma after 2.6-4.5 years, despite the absence of gross macroscopic change. The initial single layer pleomorphic high grade dysplasia in one patient regressed to low grade dysplasia which has persisted for 1.5 years. Of 10 patients with initial low grade dysplasia, one progressed to adenocarcinoma in 4.3 years. The low grade dysplasia persisted unchanged in seven patients for 1.5-7 years and appears to have regressed in two patients after three to five years. Ten patients developed low grade dysplasia during the surveillance period. This has persisted unchanged in six patients from 0.5-5 years, regressed in three for 0.5-5 years and has appeared after the first yearly biopsy in one patient. No patient without dysplasia has developed adenocarcinoma. The incidence of adenocarcinoma in Barrett's oesophagus in this study is one case per 96 patient years. This is 61 times (95% confidence limits 12-176) the age adjusted incidence of oesophageal cancer in Australia. Persistent high grade dysplasia appears to be a sensitive indicator for the development of subsequent adenocarcinoma.
Viral hepatitis A to E. An update.
The authors' aim is to present a survey of the current understanding of viral hepatitis with emphasis on hepatitis B and C and the mechanisms of prevention. Abbreviations used in this article are shown in Table 1. An overview of viral hepatitis A to E is provided in Table 2.
Improvement in chronic hepatocerebral degeneration following liver transplantation.
Chronic progressive hepatocerebral degeneration with spastic paraparesis, dementia, dysarthria, ataxia, tremor, and neuropsychiatric symptoms follows long-standing portal-systemic shunting, is associated with structural changes in the central nervous system, and does not respond to conventional therapy for hepatic encephalopathy. A case of advanced chronic liver disease with severe, progressive hepatocerebral degeneration after 23 yr of portal-systemic shunting is reported in whom there was significant objective improvement in intellectual function and in the chronic neurological signs 3 mo after orthotopic liver transplantation and further improvement 12 mo after transplantation.
Flucloxacillin induced delayed cholestatic hepatitis.
We report four cases of severe delayed cholestatic hepatitis induced by flucloxacillin. All patients presented with deep jaundice and pruritus which developed soon after ceasing flucloxacillin. Liver function tests were abnormal in all patients with markedly elevated serum bilirubin concentration, alkaline phosphatase and aspartate transaminase levels. Extrahepatic biliary obstruction and infective hepatitis were excluded in all cases. Liver biopsies showed centrilobular cholestasis with portal and lobular inflammation and eosinophil infiltration. Although symptoms resolved within six weeks in all patients, cholestatic liver function tests have persisted in two patients for more than six months. With the increasing usage of this drug and the delayed presentation of cholestasis, flucloxacillin needs to be considered in the differential diagnosis of all patients presenting with cholestatic jaundice.
Spontaneous intramural rupture of the oesophagus.
The clinical, endoscopic, and radiological features of seven patients with an uncommon oesophageal injury characterised by long lacerations of the oesophageal mucosa with haematoma formation but without perforation are reported. The injuries were not related to forceful vomiting or any other definable cause but were similar to those previously described as intramural oesophageal rupture. Upper gastrointestinal endoscopy undertaken to identify the cause of haematemesis in six patients proved safe and useful. When dysphagia and odynophagia occurred early in the clinical course to alert the clinician to possible oesophageal injury, radiological contrast studies were used to exclude perforation. One patient in this study had oesophageal cavernocapillary haemangiomatosis which may have caused intramural oesophageal bleeding and submucosal dissection but in the remainder the aetiology of intramural oesophageal rupture remains uncertain. Conservative management was successful in all patients.
Post-choledochoenterostomy 'sump syndrome'.
The 'sump syndrome' is an uncommon, late complication of a side-to-side choledochoenterostomy. Five patients with this syndrome were encountered over a 5-year period. Pain or cholangitis was the clinical presentation in four patients, whereas one patient presented with secondary septic arthritis and a hepatic abscess. Liver function tests were mildly abnormal in each patient. All patients had a stomal size of less than 1 cm as assessed by forward- or side-viewing endoscopy. Endoscopic retrograde cholangiography revealed either stones or debris in the distal common bile ducts of all patients. Four patients had a surgical clearance of their duct with concurrent closure of the choledochoduodenostomy in three patients and the creation of a Rouxen-Y end-to-side choledochojejunostomy in the fourth patient. The other patient had an endoscopic sphincterotomy performed. After 1-4 years of follow-up, four patients have had a total resolution of symptoms. The other patient with follow-up for 4 years has had one episode of cholangitis which resolved rapidly with antibiotic treatment. The pathogenesis and clinical spectrum of the sump syndrome are reviewed and current management strategies are discussed.
Postprandial antral hypomotility in patients with idiopathic nausea and vomiting.
The pathogenesis of idiopathic nausea and vomiting is poorly understood and could involve disorders of gut motility. The contractile activity of the stomach and small bowel was studied in 20 patients (seven men) with nausea and vomiting for longer than six months. None had previous gastric surgery, mechanical obstruction and metabolic causes were excluded. Fasting (four hours) and fed (up to two hours) contractile activity was recorded by a low compliance infusion system from the gastric antrum (four sites), the duodenum and the jejunum. Normal criteria were established in seven healthy controls. During fasting, from one to three (median 2) migrating motor complexes (MMC's) were present in patients and controls. Only two patients had contractile abnormalities during fasting. After a solid-liquid test meal, the contractility of the gastric antrum (quantified electronically as a cumulative motility index for 60 minutes) was significantly impaired in patients (p = 0.012). Six patients had normal qualitative and quantitative antral activity but two of them had 'phrase III-like fasting activity' in the small bowel after the test meal. Postprandial antral hypomotility was identified as a major abnormality in patients with unexplained nausea and vomiting.
Liver transplantation in Australia: the Queensland experience.
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Mortality in patients on liver transplant waiting lists: an avoidable tragedy.
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Breath hydrogen testing in bacterial overgrowth of the small intestine.
The indirect, noninvasive technique of breath hydrogen (H2) analysis was evaluated in 45 patients suspected of having bacterial overgrowth of the small intestine. Bacterial overgrowth, defined as a jejunal culture yielding at least 10(5) organisms/ml, was present in 27 patients. After dietary preparation and a 12-h fast, subjects received in random order and on separate days 50 g of glucose or 50 g of rice flour in the form of two pancakes. Normal values were established in 20 healthy controls. Twelve of 27 patients with proven bacterial overgrowth had an elevated (greater than 15 ppm) fasting breath H2 level on at least 1 test day. Fifteen of 18 patients with negative cultures had low fasting breath H2 levels. Based on values in controls, a positive breath test was defined as an increase in breath H2 of greater than or equal to 12 ppm after glucose or greater than or equal to 14 ppm after rice flour. A 2-h glucose breath H2 test had a sensitivity of 93% and a specificity of 78% in the diagnosis of overgrowth. The predictive value of a positive test was 86% and that of a negative test was 88%. The combination of both a high fasting breath H2 level and a diagnostic rise of breath H2 after glucose was present in 41% of patients with overgrowth and in none of the patients without overgrowth. Extending the test to 4 h did not increase sensitivity, but decreased specificity. Rice flour was a less satisfactory substrate in predicting the presence of bacterial overgrowth. In conclusion, a high fasting breath H2 level after dietary preparation suggests bacterial overgrowth but lacks sensitivity. The finding of a rise in breath H2 of at least 12 ppm within 2 h of a 50-g glucose challenge is a simple screen for bacterial overgrowth. The combined criteria of a high fasting breath H2 level and a significant rise after glucose are specific for bacterial overgrowth.
Campylobacter pylori and gastric antral intestinal metaplasia.
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High esophageal stricture: a complication of "inlet patch" mucosa.
High esophageal stricture associated with a circumferential "inlet patch" of heterotopic gastric mucosa is reported in 2 patients. Biopsy specimens taken from the strictures demonstrated inflamed or ulcerated gastric fundal-type mucosa in both cases. Dilatation of the strictures followed by treatment with histamine H2-antagonists produced almost complete resolution of dysphagia in both patients.