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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 505 records · Page 28Linked to original sources
PubMed1995

Intrahepatic expression of hepatitis C virus antigens in chronic liver disease.

Localization of hepatitis C virus (HCV) antigens was studied in fresh frozen and formalin-fixed, paraffin-embedded liver tissue by immunoperoxidase using monoclonal antibodies to nucleocapsid protein and polyclonal human immunoglobulin G purified from plasma containing antibodies to structural and non-structural antigens of hepatitis C virus. The results observed using monoclonal antibody to HCV core were similar to those of polyclonal IgG against HCV antigens in the majority of cases and both correlated well with HCV status as defined by 'nested' polymerase chain reaction. HCV antigens were detected in both hepatocytes and mononuclear cells. Using polyclonal human IgG, a small proportion of biliary epithelial cells were also positive in 6/29 patients. In most of the specimens examined, relatively few cells (1-5 per cent) were found to be positive for HCV antigens. The cryostat sections, using polyclonal IgG against HCV antigens, exhibited greater immunohistochemical staining, suggesting that the fixation and processing of the tissue may be a major factor in the conservation and the outcome of HCV antigen(s) findings. However, the results using monoclonal antibodies may reflect the specificity of antigen expression.

Antibodies, Monoclonal↗
PubMed1995

The effect of interleukin-6 and soluble interleukin-6 receptor protein on the bone resorptive activity of human osteoclasts generated in vitro.

The role of interleukin-6 (IL-6) in the regulation of bone resorption is controversial and has not been studied using human tissue in vitro. This study exploits a recently described in vitro model, whereby osteoclasts, defined as cells that resorb bone, can be generated from human bone marrow, and investigated the effect of IL-6 and its soluble receptor on bone resorption, in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2 vitamin D3]. Human bone marrow was cultured to form a confluent stroma, sedimented onto devitalized bone slices, and recharged with non-adherent bone marrow cells. 1,25(OH)2 vitamin D3 increased bone resorption, whereas IL-6 failed to induce a similar stimulatory effect. Both IL-6 at 100 ng/ml and soluble IL-6 receptor protein in the absence of exogenous IL-6 inhibited the stimulatory effect of 1,25(OH)2 vitamin D3. Bone resorption was never observed when non-adherent haemopoietic cells were cultured in the absence of stroma but in the presence of IL-6, which indicates that IL-6 cannot replace the stromal factor(s) required for the formation of cells capable of resorbing bone. These results suggest that IL-6 at high concentrations is not a critical cytokine in stimulating osteoclastic bone resorption.

Adult↗
PubMed1995

Use of a Gammarus pulex bioassay to measure the effects of transient carbofuran runoff from farmland.

There is now much information on the presence of pesticides in surface waters, but very little about their actual effects on aquatic life. This paper reports on the transient concentrations of a carbamate insecticide carbofuran, which were observed in a head-water stream draining treated farmland, and describes the resulting effects on a bioassay organism. One month after an application of 3 kg carbofuran/ha as broadcast granules to an oilseed rape crop, carbofuran concentrations of up to 26 micrograms/liter were measured in a nearby headwater stream after heavy rainfall. The majority of the carbofuran was translocated via field drains (where concentrations up to 264 micrograms/liter were detected), although the possibility of some surface runoff cannot be ruled out. Peak carbofuran concentrations only persisted for about 24 hr after the rainfall event, although measurable levels could be detected for at least 4 days. An in situ bioassay of streamwater which monitored the feeding rate of the gammarid amphipod crustacean Gammarus pulex showed that feeding stopped completely during the rainfall event, and was rapidly followed by death of all the caged organisms. Subsequent laboratory studies of toxicity showed that the peak concentrations of carbofuran had exceeded the G. pulex 24-hr LC50 of 21 micrograms/liter, and that concentrations as low as 4 micrograms/liter could reduce feeding rate. These findings are discussed with reference to regulatory risk evaluation procedures.

Agrochemicals↗
PubMed1995

The incidence and management of biliary complications following liver transplantation in children.

Biliary complications following liver transplantation are a cause of significant morbidity and mortality. During the period 1988-1993 ten cases of biliary complications occurred after 98 transplantations in 78 children. The complications were four bile leaks, three intrahepatic biliary strictures (one with recurrent cholangitis), two anastomotic biliary strictures (one with recurrent cholangitis) and one recurrent cholangitis. All leaks occurred within 6 weeks of transplantation whereas all strictures and cholangitic episodes occurred after 3 months. Two biliary complications (20%) - one intrahepatic and one anastomotic stricture - developed secondary to hepatic artery thrombosis. The incidence of biliary complications was 13.2% with whole liver grafts as compared to 6.7% with partial liver grafts and it was 4.3% with duct-to-duct anastomosis as compared to 12.0% with Roux-en-Y hepatico-jejunostomy. Seven children required intervention for management of biliary complications and three were managed conservatively. There were no deaths related to the biliary complications.

Adolescent↗
PubMed1995

Orthotopic liver transplantation for hepatic-based metabolic disorders.

Between January 1989 and June 1993, a total of 470 liver transplantations were performed at King's College Hospital. Thirty-seven transplantations were performed in 34 patients with liver-based metabolic disease. There were 16 females and 18 males with a median age of 19 years (range 1 month to 62 years). There were 14 patients under 16 years of age. The indications for liver transplantation were Wilson's disease (n = 16), alpha 1-antitrypsin deficiency (n = 10), tyrosinaemia (n = 2), primary hyperoxaluria type 1 (PH1; n = 2), congenital haemochromatosis (n = 1), familial amyloidotic polyneuropathy (FAP; n = 1, familial hypercholesterolaemia) (n = 1) and Crigler-Najjar syndrome type I (CNS1; n = 1). These included two patients who received combined heart-liver grafts for familial hypercholesterolaemia and FAP, respectively. Two patients received combined liver-kidney transplants for PH1. There were four deaths: from sepsis (n = 2), acute hepatic vein obstruction in a left lateral segment graft (n = 1) and portal vein thrombosis with liver necrosis (n = 1). Three patients were retransplanted, one for chronic rejection and two for hepatic artery thrombosis, giving an overall graft survival of 81% and patient survival of 88% (30/34), at a mean follow-up of 34 months (range 10-64 months).

Acute Disease↗
PubMed1995

Ribavirin therapy for hepatitis C infection following liver transplantation.

Hepatitis C infection following orthotopic liver transplantation may lead to progressive chronic graft dysfunction. In this study, seven liver transplant recipients with chronic allograft dysfunction due to hepatitis C infection (one acquired and six recurrent infections) were treated with oral ribavirin for 6 months. Symptoms of lethargy, nausea and anorexia improved in all patients within 2 weeks of starting the drug, with a fall in serum AST of at least 40% by this time. Ribavirin-induced haemolysis was clinically significant in three patients, necessitating a reduction in the daily dose of ribavirin from 1.2 g to 0.2 g. Comparison of the pre- and post-treatment biopsy specimens in the four patients who tolerated the full dose of ribavirin and who had normal AST levels at the end of 6 months of treatment showed significant histological improvement with reduction in either lobular or periportal inflammation in all of the patients and a reduction in periportal fibrosis in one patient. HCV RNA remained detectable in serum in all of the patients at the end of the study.

Female↗
PubMed1995

Differential effects of flumazenil in alcoholic and nonalcoholic cirrhotic patients.

Ligands to the benzodiazepine receptor (BZR) accumulate in hepatic encephalopathy; the benzodiazepine antagonist flumazenil can reverse some manifestations of this condition. This study was designed to explore the effects of flumazenil on cognitive function and anxiety levels in cirrhotic patients without hepatic encephalopathy. Twenty such patients--ten alcoholic, ten nonalcoholics--and ten normal volunteers matched for age and sex were randomly allocated to treatment order (flumazenil or placebo first) in a double-blind cross-over trial. Cognitive function was evaluated with a battery of psychological tests shown previously to be sensitive to the impairment induced by liver disease. Cirrhotic patients performed worse than controls on several tests: digit cancellation, digit symbol substitution, key tapping and Reitan's trail B test. Flumazenil did not reverse these cognitive impairments but it did induce anxiety in nonalcoholic cirrhotics. On one index of memory--delayed word recall--alcoholics performed worse than nonalcoholic cirrhotics. Flumazenil reversed this memory impairment in the alcoholic cirrhotic group. These results suggest that alcohol consumption induces changes at the BZR that are different from changes induced solely by liver impairment.

Adult↗
PubMed1995

Emotional processing in survivors of the Jupiter cruise ship disaster.

Twenty-three survivors of the Jupiter cruise ship disaster completed the Impact of Events Scale, a measure of intrusion and avoidance, as well as measures of arousal and affect at two points in time: between 3 and 7 months (Time 1) and between 12 and 14 months (Time 2) following the event. The aim of the present study was to explore the relationship between intrusion and avoidance and symptoms of depression and anxiety. The results suggest that although higher scores on intrusion and avoidance are strongly associated with poorer psychological outcome at each point in time, it is only intrusion which may be predictive of later symptoms. Avoidance would seem to be a response to early distress. These data are discussed with reference to a cognitive--emotional processing model of post-traumatic stress disorder.

Adaptation, Psychological↗
PubMed1995

Implicit and explicit memory for emotion-congruent information in clinical depression and anxiety.

Implicit and explicit memory biases were assessed in clinically depressed (n = 19), clinically anxious (n = 17), and normal control (n = 18) Ss. The implicit memory test was a primed lexical decision task, with anxiety- and depression-relevant words, and suprathreshold and subthreshold primes. The explicit memory test was incidental free recall of self-referenced words. The depressed group showed greater suprathreshold and subthreshold priming effects for depression words, and recalled more depression words, than the other two groups. These results suggest that clinical depression, but not clinical anxiety, is associated with mood-congruent biases in both automatic and strategic memory processes.

Adolescent↗
PubMed1995

Thirty-five years of paediatric scalds: are lessons being learned?

All paediatric scalds admitted in 1991 to the Welsh Centre for Burns and Plastic Surgery have been analysed retrospectively and the results compared with similar studies from this centre reported in 1956 and 1984. This data was compared with similar reports from 6 other world-wide centres. Despite a modest population increase in Wales, the number of admissions has increased almost 50% in 35 years. Boys are more commonly affected and up to 67% of scalds occur in children under 2 years of age. The number of scalds from teapots has fallen from 20.8% to 2.7%, in contrast to scalds from cups of hot liquid which have increased from 8.9% to 42.5% over the 35-year period. Scalds from hot baths are rare in Holland and Denmark, in contrast to a 15.8% incidence in our centre. Hot kettles are a common cause of scalds, accounting for up to 28% of scalds in all the series reviewed. The incidence of this injury has not decreased over the last 35 years. Recommendations are made about improved health and safety education for parents, the use of coiled kettle flexes, the temperature of stored water which should not exceed 60 degrees C, and the fitting of thermostatic mixer taps to new houses and institutions, in an effort to decrease the incidence of paediatric scalds.

Accident Prevention↗
PubMed1995

Genomic variations in the hepatitis B core gene: a possible factor influencing response to interferon alfa treatment.

BACKGROUND/AIMS: Interferon treatment causes a sustained loss of virus replication only in a proportion of patients with chronic hepatitis B. This study investigated whether genomic variations in the precore/core gene of hepatitis B virus affect the response to interferon alfa. METHODS: The precore/core region was sequenced in 46 serum samples obtained before, during, and after interferon treatment of 12 patients. RESULTS: In 23 samples from 7 responders (group A), there were 24 missense mutations, whereas in 23 samples from 5 patients who did not respond or relapsed after treatment (group B), there were 141 missense mutations (P < 0.001). All group B patients had cirrhosis, but only 2 of 7 patients in group A had cirrhosis (P = 0.026). Substitutions in amino acids 21-27 of the core protein, known to diminish HLA-A2-restricted cytotoxic T-cell function, were found in all nonresponders but in none of the responders. No significant changes occurred in the precore/core region in responders after seroconversion to antibody to hepatitis B e antigen, but multiple variations persisted in group B during treatment and new mutations appeared with the relapse of hepatitis. CONCLUSIONS: Specific mutations in the core protein that can interfere with T-cell function occur frequently in patients with advanced chronic hepatitis B and may affect the response to interferon.

Adult↗
PubMed1995

The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy.

BACKGROUND/AIMS: Quinolinic acid is an endogenous neuroexcitant derived from tryptophan. Brain quinolinic acid concentrations are reportedly elevated in chronic liver failure. The aim of this study was to determine if brain quinolinic acid levels correlate with the severity of hepatic encephalopathy. METHODS: Postmortem samples of selected brain regions and plasma samples taken at several stages of encephalopathy were obtained from patients with acute and chronic liver failure. Quinolinic acid levels were measured by mass spectroscopy using [18O]quinolinic acid. RESULTS: Plasma quinolinic acid levels were significantly increased by stage I encephalopathy in patients with acute liver failure and by stages II and III in patients with chronic liver failure. Brain quinolinic acid levels were elevated only in patients with acute liver failure and were uniformly distributed at concentrations below those observed in plasma. CONCLUSIONS: The uniform distribution of quinolinic acid at subplasma concentrations in the brains of patients with acute liver failure suggests that it is synthesized peripherally and enters the brain across a permeabilized blood-brain barrier. Whereas the elevation of brain quinolinic acid levels in patients who died of acute but not chronic liver failure suggests that the involvement of quinolinic acid in the pathogenesis of hepatic encephalopathy is minimal, it could predispose these patients to seizures.

Acute Disease↗
PubMed1995

Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis.

BACKGROUND/AIMS: The diagnosis of cholangiocarcinoma in primary sclerosing cholangitis (PSC), even with the use of current imaging techniques and brush cytology, is difficult and particularly important in patients being assessed for liver transplantation. This study investigated the accuracy of serum levels of a combination of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in the diagnosis of cholangiocarcinoma in patients with PSC. METHODS: Seventy-four patients with PSC were studied. Fifteen patients had tumors (11 occult on imaging), 22 had severe PSC that necessitated transplantation (with explanted liver known to be free of tumor), and 37 patients had stable PSC. RESULTS: An index of the two serum tumor markers [using the formula CA19-9 + (CEA x 40)] gave an accuracy of 86% in diagnosis of cholangiocarcinoma, with 10 of the 15 cases of cholangiocarcinoma having an increased value compared with none in a group of 22 comparable cases with no tumor. In addition, 6 of the 11 patients with occult tumors had abnormal values. Ultrasonography, computerized tomographic scanning, and endoscopic retrograde cholangiopancreatography were poor predictors of the presence of tumor. CONCLUSIONS: A combination of serum tumor markers will identify most occult tumors and will improve selection of appropriate cases for orthotopic liver transplantation.

Adult↗
PubMed1995

Massive ascitic fluid loss and coagulation disturbances after liver transplantation.

BACKGROUND & AIMS: A unique syndrome in which massive ascitic fluid loss developing 1-4 weeks after orthotopic liver transplantation (OLT) was associated with a hypercoagulable state and thrombotic complications is described. After OLT, severe coagulation abnormalities (international normalized ratio, 4.6) developed in a patient with ascitic losses of up to 12 L/day. The patient developed hypovolemia and severe systemic antithrombin III deficiency and venoocclusive disease in the graft. The aim of this study was to determine the prevalence of this syndrome after OLT. METHODS: Coagulation studies were performed in 25 additional patients with large ascitic fluid losses after OLT and in 7 cirrhotic patients not undergoing transplantation. RESULTS: All transplant recipients developed systemic deficiencies of multiple coagulation factors including antithrombin III. Markers of prothrombin activation were significantly elevated in both ascites and serum in all patients, and thrombotic complications subsequently developed in 5 patients. In the 7 cirrhotic patients, markers of prothrombin activation remained normal or minimally elevated and thrombotic complications were not found. CONCLUSIONS: Massive ascitic losses after OLT may lead to a hypercoagulable state from unreplaced losses of plasma coagulation factors into ascites and accumulation of thrombin in the systemic circulation. Hypovolemia and major coagulation abnormalities should be corrected with fresh frozen plasma, which may prevent the development of thrombotic complications.

Adult↗
PubMed1995

Tumor necrosis factor receptors in patients with chronic hepatitis B virus infection.

BACKGROUND/AIMS: Patients with chronic hepatitis B infection have elevated plasma tumor necrosis factor (TNF) alpha levels. Two TNF-alpha receptors have been identified, each responsible for distinct TNF-alpha activities. The aim of this study was to evaluate the biological function of the elevated TNF-alpha in chronic hepatitis B virus infection by examining the two TNF signaling pathways in the evolution of hepatitis B-related liver injury. METHODS: The hepatic expression of the two TNF receptors and the corresponding serum levels of the soluble forms of both TNF receptors were determined and correlated with hepatic inflammation and virus replication in 98 chronic hepatitis B surface antigen carriers. Forty hepatitis B e antigen-positive patients were also studied prospectively, while on interferon alfa treatment, to examine the TNF receptor response during viral clearance. RESULTS: In chronic hepatitis B virus infection, the hepatic expression and serum levels of TNF receptors, in particular 75-kilodalton TNF receptor subtype (TNF-R p75), are significantly enhanced in association with hepatic inflammation and hepatocytolysis but not with hepatitis B virus replication. During interferon alfa treatment, a significant increase of soluble TNF-R p75 always precedes the hepatitis B e antigen antibody against hepatitis B e antigen seroconversion in responders to treatment. CONCLUSIONS: In chronic active hepatitis B infection, there is an up-regulation of the TNF receptor system, preferentially the TNF-R p75 signaling pathway, which suggests that the TNF-alpha/TNF receptor system has an important role in the pathogenesis of liver damage and viral clearance.

Antigens, CD↗
PubMed1995

A 7-year experience of severe acetaminophen-induced hepatotoxicity (1987-1993).

BACKGROUND & AIMS: Five hundred sixty patients admitted between January 1, 1987, and December 31, 1993, with severe acetaminophen-induced hepatotoxicity were studied. The aim of this study was to identify why severe acetaminophen-induced hepatotoxicity still occurs and to determine how known risk factors and advances in management have affected the pattern of illness and outcome. METHODS: This was a retrospective study of the etiologic factors and the clinical course of all acetaminophen-related admissions. RESULTS: The number of admissions increased from 58 in 1987 to 123 in 1993. During the corresponding period, overall survival improved from just < 50% to 78%. The percentage of admissions treated with N-acetylcysteine increased from 40% in 1987 to 83% in 1993. The frequency with which grade III or IV encephalopathy developed decreased from 62% in 1987 to 40% in 1993, and the percentage of these patients who developed cerebral edema decreased from 61% to 45% during the same period. There was an increase in both the number of patients transplanted and the survival of those managed medically. CONCLUSIONS: Severe acetaminophen-induced hepatotoxicity remains a serious condition, but the increasing use of N-acetylcysteine, advances in medical management, and the increasing availability of transplantation have resulted in a significant improvement in survival rates.

Acetaminophen↗
PubMed1995

Late-onset hepatic failure: clinical features, serology and outcome following transplantation.

A further series of 41 adult patients with late-onset hepatic failure was investigates with respect to aetiological factors, particularly hepatitis C and E, which have been identified since our earlier report of this condition. The increased use of transplantation and its impact on survival overall is assessed. Comparison is made with 64 patients admitted over the same period with fulminant hepatic failure of non-A, non-B aetiology. Screening for the hepatitis viruses revealed three cases of hepatitis A and one case of Epstein Barr virus hepatitis. There were no cases of hepatitis C or hepatitis E virus detected by enzyme immunoassay and reverse transcriptase/polymerase chain reaction techniques, although three patients had positivity for IgG anti-hepatitis E virus, demonstrating previous exposure. Serum autoantibodies in a titre greater than or equal to 1:40 were present in 29% of samples tested and in three cases, titres of SMA or ANF were greater than 1:320. In a further five cases, a potentially hepatotoxic agent had been given within 3 months of the onset of symptoms, leaving the majority of patients (29) with no identifiable cause for their disease. The frequency of symptoms, however, including nausea, abdominal discomfort with the subsequent development of ascites, encephalopathy and renal impairment suggest a similar disease process in these patients. Analysis of liver biopsy material showed similar patterns on all cases of map-like necrosis with nodular regeneration and without other additional features of aetiological significance. Differences in clinical and histological changes for the non-A, non-B fulminant hepatic failure comparison group reflect the tempo of disease process rather than the nature and cause of the liver damage. The introduction of transplantation has led to a marked improvement in survival (39% overall in the earlier series). In the 21 patients in whom transplantation was carried out, the 1-year actuarial survival is currently 55%. Treatment of late-onset hepatic failure with corticosteroids and the use of Prostaglandin E1 and interferon in individual cases has been disappointing, and the emphasis in management should be placed on teh early referral of such patients to a centre offering transplantation.

Adolescent↗