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Biomedical subjects

A K Burroughs

Publications and source records attributed to A K Burroughs.

At least 199 records · Page 11Linked to original sources
PubMed1993

The pharmacokinetics of intravenous ondansetron in patients with hepatic impairment.

The pharmacokinetics of the 5-HT3 receptor antagonist ondansetron were investigated following a single 8 mg intravenous dose given over 5 min in 19 patients with varying degrees of hepatic impairment and in six young healthy subjects. In comparison with the healthy controls, the patients with severe hepatic impairment had a lower mean plasma clearance (96 ml min-1 vs 478 ml min-1) and increased AUC (1383 ng ml-1 h vs 279 ng ml-1 h) and t1/2 (21 h vs 3.6 h). These differences were all statistically significant (P < 0.001). The corresponding values for patients with mild or moderate hepatic impairment fell between these extremes. Vss was greater in all patient groups than the control group, but the magnitude of the change was smaller than for the other parameters and did not reflect the increasing severity of hepatic impairment. There were no significant changes in Cmax. There were no drug-related adverse events in the patients studied. It is recommended that the dosing frequency of ondansetron be limited to once daily in patients with severe hepatic impairment.

Adult↗
PubMed1993

Endoscopic extraction of bile duct stones: management related to stone size.

Endoscopic sphincterotomy has become the first line treatment for patients with common bile duct (CBD) stones. This technique may fail, however, due to difficult anatomy, previous surgery, periampullary diverticula or the presence of a large stone. The importance of stone size to the success of endoscopic sphincterotomy has not been fully assessed. A prospective study was carried out over the period January 1987 to December 1989 on 100 patients (45 male, 55 female, median age 69 years, range 19-97) with CBD stones in which a policy of early duct clearance was followed. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and the stone size and number recorded from the cholangiograms and corrected for magnification. Sphincterotomy was performed using a diathermy unit with a cutting current and stones were extracted using a balloon catheter or a Dormia basket. Of the 100 patients with CBD stones receiving ERCP, successful clearance of the biliary tree was possible in seven without endoscopic sphincterotomy and five were felt to be unsuitable for endoscopic sphincterotomy. Of the remaining 88 patients endoscopic sphincterotomy was successful in 75 (85%). Of the 75 patients having endoscopic sphincterotomy stone clearance was successful in 44 (59%). There were no deaths and only four complications, which rapidly resolved on conservative treatment (two acute pancreatitis, two bleeding). The number of CBD stones present was similar in those patients with successful endoscopic sphincterotomy and duct clearance (median 1, range 1-10, n = 44) as in those in whom it failed (median 2, range 1-6, n = 31). In contrast there was a highly significant difference when stone size was analysed (successful clearance median stone size 10 mm, range 3-27 mm; unsuccessful: median 18 mm, range 10-42, p<0.001). Stones less than 10 mm in diameter (n=21) were all removed successfully whereas in patients with stones over 15 mm (n=25) only three were removed endoscopically (12%). All patients with evidence of residual stones had additional treatment. Of these 31 patients, 10 had surgery, 11 had insertion of an endoprosthesis, and 10 had dissolution treatment with methyl-tert-butyl ether through a nasobiliary catheter. This study shows the importance of stone size to the success rate of endoscopic removal of bile duct stones.

Adult↗
PubMed1993

Pulmonary platelet aggregates: possible cause of sudden peroperative death in adults undergoing liver transplantation.

AIMS: To determine if massive pulmonary platelet thromboembolism is a common cause of peroperative death following liver transplantation; and to compare the incidence of this event with patients dying after non-transplantation procedures. METHODS: Necropsy tissues from all patients dying within 10 days of operation during the past three and a half years were studied (six liver transplantations and 13 unrelated operations). Haematoxylin and eosin stained sections of all tissues were examined. Additional sections of lung tissue were immunostained for constituents of thrombus (fibrin and platelets). RESULTS: At necropsy the lungs from all six liver transplant recipients were heavy with a rubbery texture and little oedema fluid. Those from non-transplantation patients appeared normal or very oedematous. Microscopic examination showed that there were numerous platelet aggregates occluding pulmonary capillaries in all six transplant recipients, but in only three of the non-transplant patients. These thrombi were numerous in patients dying during surgery and the number was underestimated in routine sections because of the surrounding capillary congestion. Detection was improved by immunostaining for platelets with factor XIIIA and platelet glyco-protein IIIa. CONCLUSIONS: Massive platelet thromboembolism is a likely cause of death in patients dying unexpectedly following recent liver transplantation. Non-transplantation patients dying during surgery who show similar appearances usually have conditions known to have a high risk of thrombosis or embolism (cement hypotension syndrome and disseminated intravascular coagulation). The cause of this extensive platelet activation in liver transplant recipients is uncertain and may be multifactorial. The unusual rubbery consistency of the lungs on macroscopic examination could alert the pathologist to the underlying condition. Immunostaining for platelets improves the detection microscopically.

Adult↗
PubMed1993

Liver/spleen scintigraphy for diagnosis of splenic infarction in cirrhotic patients.

Splenic infarction is rare in cirrhotic patients. The diagnosis of the condition is based on clinical findings and splenic imaging. In recent years, ultrasonography and computed tomographic scan have gained popularity over the more classical scintigraphy as the preferred investigations for the diagnosis of splenic infarction. We report three cases of splenic infarction in patients with cirrhosis and portal hypertension. Computed tomographic scan, angiography and ultrasonography failed to identify the lesions and the diagnoses were finally made with the aid of liver--spleen scintigraphy. We suggest that scintigraphy is the investigation of choice if splenic infarction is suspected in patients with congestive splenomegaly secondary to liver cirrhosis.

Adult↗
PubMed1993

Potential indications for octreotide in gastroenterology: summary of workshop.

The potential therapeutic applications of somatostatin and octreotide in gastroenterology involve gut neuro-endocrine tumours, bleeding varices, bleeding peptic ulcers, gastro-intestinal fistulae, pancreatic fistulae, dumping syndrome, pancreatic pseudocysts, short bowel syndrome, acute pancreatitis, AIDS-related diarrhoea, intestinal subacute obstruction, idiopathic 'diarrhoea', irritable bowel syndrome and GIT tumours. Octreotide has a longer duration of action than somatostatin and can be administered by subcutaneous injection, thus making it suitable for long-term administration. Many of the potential gastro-intestinal indications require long-term administration and thus octreotide would be the agent of choice.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Liver transplantation during pregnancy.

We present a case of successful liver transplantation during the midtrimester of pregnancy, showing that pregnancy itself is not a contraindication to liver transplantation with life-threatening illness. Improvements in anaesthetic and surgical technique will enhance the possibility of foetal survival.

Adult↗
PubMed1992

Prediction of short-term survival with an application in primary biliary cirrhosis.

Many long-term follow-up studies for survival accumulate repeated measurements of prognostic factors. Survival models which include only covariate values at baseline do not use all available information, and do not relate to survival predictions for times other than at that baseline. Time-dependent covariate models (which update covariate values as measurements occur through time) might be used, though limitations of software for estimating the underlying hazard functions and difficulty in relating hazard function changes to survival prediction present serious drawbacks. By dividing each patient's follow-up into successive intervals of equal length (using a length of interest for prediction) and with measurements available at the start of each, we describe how an analysis taking person-intervals as the observation units can be undertaken using readily available software to produce short-term survival models. We show that this approach is related to both the baseline and time-dependent covariate models. The method is illustrated using data from a long-term study of patients with primary biliary cirrhosis, where interest is in short-term survival predictions to aid the decision when to undertake liver transplantation.

Humans↗
PubMed1992

Treatment of small hepatocellular carcinomas.

There is growing interest in screening to detect symptomless hepatocellular carcinoma (HCC), which should be easier to treat than symptomatic tumours. Combined alpha-fetoprotein and ultrasound monitoring can detect HCCs of 1 cm, and Lipiodol retention can be detected in tumours smaller than 1 cm. A number of treatment options are available. Surgical resection may be curative in selected patients with a single small tumour, but the cirrhotic patient is left with a diseased liver and the risk of tumour recurrence or death from underlying liver dysfunction. Orthotopic liver transplantation is a rational treatment for patients with decompensating cirrhosis and a small HCC, but it is expensive and necessitates immunosuppression. A variety of targeted or local therapies, either individually or in combination, can be used to treat HCC. These include percutaneous alcohol injection into an HCC, which may be an alternative to surgical resection. Tumour necrosis can be seen after targeted Lipiodol chemotherapy or radiotherapy. Transcatheter arterial embolisation selectively embolises the feeding artery, and can be combined with Lipiodol chemotherapy. Small tumours are thus amenable to treatment, even in patients who cannot have surgery. Screening and treatment for symptomless HCC seems justified, unless controlled trials teach us differently.

Antineoplastic Agents↗
PubMed1992

Prevention of first bleeding in cirrhosis. A meta-analysis of randomized trials of nonsurgical treatment.

OBJECTIVE: To assess the effectiveness of beta-blockers and endoscopic sclerotherapy in the prevention of first bleeding and reduction of mortality in patients with cirrhosis and esophagogastric varices. DATA SOURCES: Pertinent studies were selected using MEDLINE (1980 to 1990), reference lists from published articles or reviews, and congress abstract lists. STUDY SELECTION: Randomized trials comparing beta-blockers or sclerotherapy with a nonactive treatment. Nine randomized clinical trials of beta-blockers and 19 trials of sclerotherapy were reviewed. Seven trials of beta-blockers and 15 of sclerotherapy were published as full papers. DATA EXTRACTION: Crude rates of bleeding and death in treated and control groups were extracted from each trial by three independent observers according to the intention-to-treat principle. The quality of published papers was systematically assessed and scored. DATA SYNTHESIS: The Mantel-Haenszel-Peto method was used for statistical evaluation of heterogeneity and for pooling of the results. No substantial heterogeneity was found, and the incidence of bleeding in trials of beta-blockers was significantly reduced (pooled odds ratio, 0.54; 95% CI, 0.39 to 0.74), particularly in patients with large or medium-sized varices or in those with varices and a hepatic vein pressure gradient above 12 mm Hg; however, only a trend toward reduced mortality was obtained. Sclerotherapy trials were highly heterogeneous in the direction of the treatment effects on both bleeding (pooled odds ratio, 0.6; CI, 0.49 to 0.74) and mortality (pooled odds ratio, 0.76; CI, 0.61 to 0.94). The quality of the trials and the rate of bleeding in the untreated groups were the major sources of heterogeneity. The favorable results of sclerotherapy were obtained in trials with high bleeding rates among controls; several of these trials had a low quality score. CONCLUSIONS: Beta-blockers may be recommended for prevention of first bleeding in cirrhotic patients with varices who have a high risk for bleeding. The effectiveness of sclerotherapy remains undetermined. Further trials in high-risk patients may prove useful if improved criteria to predict bleeding risk become available.

Adrenergic beta-Antagonists↗
PubMed1992

Esophageal staple transection as a salvage procedure after failure of acute injection sclerotherapy.

It is not clear which therapy should be used in patients with bleeding esophageal varices that are not controlled by emergency sclerotherapy. This is a high-risk group with reported mortality rates of between 70% and 90%. We report our 7-yr experience with staple transection of the esophagus in this patient group. Of 168 patients (280 bleeding episodes) treated with sclerotherapy, 22 had emergency staple transection for failure to control bleeding. Bleeding was controlled in 20 patients (90%), and 10 patients (45%) survived to leave the hospital, including 4 of 10 patients (40%) with Pugh grade C liver disease. We suggest that emergency staple transection is an effective salvage treatment for this high-risk group.

Emergency Medical Services↗
PubMed1992

Bleeding from staple line erosion after esophageal transection: effect of omeprazole.

Esophageal staple transection effectively controls acute variceal bleeding, but up to 50% of these patients will have recurrent upper gastrointestinal bleeding. In our experience, most of these bleeding episodes are caused by total or partial circumferential ulceration at the level of the staple transection: staple line erosion. It caused rebleeding in 29 (40%) of our patients. Whereas the pathogenesis of this lesion is unknown, acid reflux is a consequence of transection surgery. Assuming that staple line erosion could be healed by acid suppression therapy, thereby preventing recurrent bleeding, an acid suppression regimen was evaluated prospectively in 24 patients. Only six (25%) healed with daily standard (300 mg) or high-dose (1,200 mg) ranitidine combined with sucralfate (4 gm). The remaining 18 (75%) healed after omeprazole administration (40 mg/day) for 1 mo. Maintenance ranitidine alone (300 mg/day) was introduced, but 11 (48%) had relapse of erosions. All 11 healed with omeprazole (40 mg/day) for 2 mo, but again on maintenance ranitidine, 10 relapsed. All healed with further omeprazole and healing persisted with long-term administration (20 mg/day). Fifteen rebleeding episodes occurred in eight patients on maintenance ranitidine. Whereas relapse of staple line erosions did occur in the absence of rebleeding, all rebleeding episodes were associated with the relapse of staple line erosion. Omeprazole is more effective than ranitidine alone and combined with sucralfate in healing staple line erosion. Omeprazole prevents rebleeding, which may enhance the long-term benefits of staple transection for acute variceal bleeding.

Adult↗
PubMed1992

Immunohistochemical studies on the innervation of human transplanted liver.

The changing pattern of innervation in the human transplanted liver was studied from the day of transplantation to 5 years later. Seven liver biopsies from non-transplant controls, 37 liver biopsies from 22 transplant patients, and one of these biopsied livers removed at retransplantation, were available for the study. Sections were immunostained for protein gene product 9.5 (PGP 9.5), neurone-specific enolase (NSE), S-100 protein, and vasoactive intestinal polypeptide. NSE and PGP 9.5 demonstrated nerves most successfully in our tissues. Staining for most small nerves was reduced by day 5 post-transplantation. Scanty fine nerves could be detected from day 13 to day 241 in occasional biopsies. Consistently identifiable immunostaining of PGP 9.5 and NSE nerve fibres was again apparent in portal areas after this time in all but one case. The findings indicate that in transplanted liver limited reinnervation can eventually take place. This could be due to either proliferation of intrinsic nerves, or regrowth of extrinsic nerves, or both.

Humans↗
PubMed1992

The effects of alcohol use on rebleeding and mortality in patients with alcoholic cirrhosis following variceal haemorrhage.

The effect of continued alcohol intake on prognosis in alcoholic cirrhotics who have already bled from varices is controversial. To investigate the effect of alcohol intake on prognosis we studied 189 consecutive alcoholic cirrhotics admitted, for the first time, to the Royal Free Hospital with variceal bleeding. Sixty-six died within 30 days of admission and 23 were excluded from the study for other reasons. Of the 100 remaining 15 remained 'probably abstinent' over long-term follow-up, 29 drank occasionally and 56 continued to misuse/abuse alcohol. The percentage survival probability at 2 years was 66% in the probable abstainers, 68% in the occasional drinkers and 63% in the alcohol abuse/misuse group. There were no significant differences in either mortality or rebleeding rates between the three groups. A rebleeding index (designed to take account of the number of rebleeds per patient and the total length of follow-up) also failed to show any significant difference between the three groups. The Cox proportional hazard model was used to study the effect of the following factors on rebleeding and mortality; age, sex, alcohol use, Pugh's score, acute treatment received for initial variceal bleed and long-term treatment received for prevention of recurrent variceal haemorrhage. Pugh's score was significantly related to risk of death during follow-up (p = 0.0122), but none of the other factors was significantly related to risk of rebleeding or mortality. Using conventional methods to determine alcohol use we were unable to demonstrate significant effects of alcohol intake on rebleeding or mortality in alcoholic cirrhotics who had bled from oesophageal varices.

Alcohol Drinking↗