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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 343 records · Page 19Linked to original sources
PubMed1997

Detection of Maedi-Visna virus antibodies using a single fusion transmembrane-core p25 recombinant protein ELISA and a modified receiver-operating characteristic analysis to determine cut-off values.

The core p25 and transmembrane (TM) genes of Maedi-Visna virus (MVV) were cloned individually into the pGEX-2T expression vector. Both proteins were expressed as a combined fusion protein in frame with glutathione S-transferase (GST). The purified recombinant antigens (GST-TM and GST-TM-p25) were used to develop a MVV ELISA. A preliminary assessment of the diagnostic potential of the recombinant antigens (GST-TM and GST-TM-p25) was made by testing the antigens against 46 seropositive and 46 seronegative sheep and comparing the results with a commercial p25 ELISA kit. A two-graph receiver operating characteristic (TG-ROC) analysis program was used to interpret the data. The GST-TM-p25 ELISA was more sensitive than the commercial assay which is based on the p25 antigen alone and more specific than the GST-TM ELISA.

Animals↗
PubMed1997

Auxiliary partial orthotopic liver transplantation for acute liver failure.

BACKGROUND/AIMS: Auxiliary partial orthotopic liver transplantation holds potential advantages over conventional orthotopic liver transplantation, but experience with the technique in acute liver failure is limited. METHODS: We describe our initial experience in seven patients (4 men, 3 women; mean age 28, range 14-35 years) with acute liver failure (paracetamol 3, non A-E 2, autoimmune 1, Ecstasy 1) who fulfilled criteria for emergency transplantation. Preoperatively, the median international normalised ratio was seven (range 3.4-15), with a creatinine of 123 microM (51-389 microM) and bilirubin 320 microM (61-572 microM). The reasons for performing an auxiliary transplant were the patients' young age and stable preoperative condition (n = 5), or a significant psychiatric history precluding conventional transplantation (n = 2). RESULTS: All patients received blood group-matched left (n = 2) or right (n = 5) auxiliary grafts. Median duration of surgery was 8.5 h (7.3-10 h), with blood loss of 8.3 litres (4.6-14.6 litres). Post-transplant, the international normalised ratio and aspartate aminotransferase fell progressively in all patients, with median values at day 7 of 1.4 (1.0-2.4) and 108 IU/1 (78-910 IU/1). Three patients died from sepsis within the first postoperative month. At 2 weeks, four of six patients had partial regeneration of the native liver, which became complete in two of the survivors by 1 year. CONCLUSIONS: Although patient selection remains poorly defined, auxiliary partial orthotopic liver transplantation in acute liver failure is technically feasible and, in some patients, allows native liver regeneration and eventual immunosuppression withdrawal.

Acute Disease↗
PubMed1997

The clinical diversity and role of chemotherapy in lymphoproliferative disorder in liver transplant recipients.

BACKGROUND/AIMS: Post-transplant lymphoproliferative disorder is a well-documented complication with an incidence ranging from 2 to 10%, depending on the organ transplanted. Yet despite our increased understanding of the pathophysiology of this disease and the various treatments available, the mortality remains high at 60-80%. We present the clinical and histological features of ten adult liver transplant recipients with post-transplant lymphoproliferative disorder presenting over a 15-year period and review the therapeutic options. METHODS: CD20/CD45RO immunostaining was used for T/B-cell markers; polymerase chain reaction and in-situ hybridisation for Epstein-Barr virus genome detection; kappa/lambda immunostaining and gene rearrangement analysis for clonality. RESULTS: There were six females and four males (age range 24-56) with onset of post-transplant lymphoproliferative disorder-symptoms ranging from 3 to 72 months post transplant. Sites of post-transplant lymphoproliferative disorder included liver (n=4), lymph nodes (n=5), bone marrow (n=2), lungs (n=2), kidneys (n=2), brain, ovaries,: and pancreas (n=1). All lesions were classified as high-grade lymphoma, of B-cell lineage (9 tested); Epstein-Barr virus genome was detected in 7/10 cases. Three tumours were monoclonal; four were polyclonal and three undetermined. Treatment included immunosuppression reduction, antiviral therapy with acyclovir and/or chemotherapy (CHOP or VAPEC-B). Survival times for those patients not treated with chemotherapy were from 9 days to 30 months, whereas those receiving chemotherapy had remission times of 4 to 48 months. CONCLUSIONS: Longer-term remissions can be achieved in patients treated with systemic chemotherapy, although not without morbidity. Clonality assessment is important but treatment decisions should be based primarily on clinical features of progression, as polyclonal tumours can behave as aggressively as monoclonal tumours.

Adult↗
PubMed1997

Hepatitis C virus infection in the development of hepatocellular carcinoma in cirrhosis.

BACKGROUND/AIMS: The role of hepatitis C virus replication and different genotypes in the progression of cirrhosis to hepatocellular carcinoma is examined on the basis of a prospective follow-up of 1438 patients with histologically proven cirrhosis. METHODS: The presence of HCV RNA, anti-HCV and characterisation of virus genotypes were determined in 72 cases who developed hepatocellular carcinoma after a median follow-up of 5.3 years (range 1 to 16) and compared to 72 controls who had cirrhosis only, after a median follow-up of 4.8 years (range 1 to 16). Patients in the hepatocellular carcinoma group and controls were matched, one to one, for age, sex, nationality, HBsAg seropositivity, duration of follow-up and aetiology of cirrhosis. RESULTS: HCV RNA was detected in 31 of 72 (44%) patients who developed hepatocellular carcinoma, significantly more frequently than in 17 of 72 (23%) controls with cirrhosis (odds ratio 2.4, 95% confidence interval 1.2 to 5.0; p = 0.013). When cirrhosis of different aetiologies was analysed, hepatitis C virus replication was more frequently detected in patients developing hepatocellular carcinoma in association with cryptogenic cirrhosis (p = 0.007), alcoholic cirrhosis (p = 0.043) and hepatitis B virus seronegative cirrhosis (p = 0.05). Hepatitis C virus genotypes 1b and 4 were the most prevalent; they were found in 53% and 25%, respectively, of the patients studied, but were equally distributed between cirrhosis progressing to hepatocellular carcinoma and controls. CONCLUSIONS: Persistent hepatitis C virus replication is closely associated with hepatocellular carcinoma development in cirrhosis, and there is no preferential role of individual hepatitis C virus genotypes.

Adult↗
PubMed1997

Hepatitis B virus sequence changes evolving in liver transplant recipients with fulminant hepatitis.

BACKGROUND/AIMS: Patients undergoing liver transplantation for hepatitis B virus (HBV) related liver cirrhosis are at major risk of developing HBV recurrence, and occasionally fulminant hepatitis. Here we tested in a longitudinal study whether specific viral variants are associated with fulminant HBV infection in the graft. METHODS: The complete HBV genomes isolated from the sera of three patients with HBV and HBV and hepatitis delta virus (HDV) coinfection during chronic infection before and during fulminant reinfection after transplantation were amplified and directly sequenced. RESULTS: Twenty, 25 and 19 mutations, distributed over the entire genome, were identified which differed between the HBV genomes isolated from each patient during chronic and fulminant infection, respectively. This reflects a much higher rate of nucleotide sequence changes than expected from the natural variation of HBV. No common HBV mutation emerged in any of the three cases during fulminant infection. However, precore defective viruses were found to be present in all three patients at the time of fulminant infection and in two of the patients before fulminant infection. Two of the patients had preS2-defective HBVs both before and after transplantation. A point mutation in the 'a'-determinant of the surface protein emerged in one case after transplantation under treatment with polyclonal HBV specific immunoglobulins. CONCLUSIONS: Many new, but no specific common mutations emerged during fulminant HBV reinfection. Although HBeAg defective variants were found in all cases studied, the presence of these variants also during chronic infection in two cases demonstrates that they are not sufficient to cause fulminant hepatitis. Thus, other factors than the emergence of a specific viral strain seem to contribute to the development of fulminant reinfection in a liver graft.

Adult↗
PubMed1997

Plasma levels and hepatic mRNA expression of transforming growth factor-beta1 in patients with fulminant hepatic failure.

BACKGROUND/AIMS: Transforming growth factor-beta1 is an important cytokine involved in cell growth and inflammation which has been shown to be inhibitory to hepatic DNA synthesis. The aim of this study was to investigate the plasma levels and hepatic mRNA expression of transforming growth factor-beta1 in patients with fulminant hepatic failure in whom liver regeneration may be impaired. METHODS: Plasma levels of transforming growth factor-beta1 and human hepatocyte growth factor were measured in 57 fulminant hepatic failure patients and 20 healthy volunteers by ELISA. Northern blot analysis of transforming growth factor-beta1 and H3 histone, a marker for liver proliferation, was performed in liver tissue of 14 fulminant hepatic failure patients. RESULTS: The plasma levels of total transforming growth factor-beta1 in fulminant hepatic failure patients on admission (median 38.8 ng/ml, range 8.4-108 ng/ml) were significantly higher than those in control subjects (23.0 ng/ml, 8.5-34.9 ng/ml, p<0.001). Significantly higher levels were observed in non-A, non-B hepatitis patients (57.9 ng/ml, 38.8-108 ng/ml, n=10, p<0.001) compared to patients with paracetamol overdose (37.1 ng/ml, 8.4-72.5 ng/ml, n=47). In contrast, the plasma levels of free transforming growth factor beta1 were greater in paracetamol overdose (623 pg/ml, 46.7-1241 pg/ml, n=21) than in non-A, non-B hepatitis (131 pg/ml, 77.2-254 pg/ml, n=9), with both being higher than control (72.3 pg/ml, 28.7-108, n=7, p<0.001). The plasma levels of human hepatocyte growth factor in patients with paracetamol overdose (7.04 ng/ml, 1.00-62.4 ng/ml) were significantly higher than those in patients with non-A, non-B hepatitis (4.48 ng/ml, 0.74-9.10 ng/ml, p<0.05). Northern blots showed increased mRNA expression of transforming growth factor-beta1 in paracetamol-overdose patients (n=8, p<0.05), but not in patients with non-A non-B hepatitis (n=6), compared to controls (n=4). CONCLUSIONS: The increased circulating plasma TGF-beta1 in FHF may be part of the tissue repair process in fulminant hepatic failure. In patients with non-A, non-B hepatitis, the increased total transforming growth factor-beta1 together with a less elevated hepatocyte growth factor could be related to impaired liver regeneration in this group.

Acetaminophen↗
PubMed1997

Morbidity and Irish Catholic descent in Britain: an ethnic and religious minority 150 years on.

Ethnic and religious minorities often suffer disadvantages both in socio-economic status and in health. Data from the West of Scotland Twenty-07 study suggest some differences in morbidity between those descended from Irish Catholic migrants of the great emigration from 1840 onwards and others. Catholic religion of at least one parent or at birth is used here as a proxy measure to indicate Irish Catholic descent, on the basis of estimates of sensitivity and specificity in the local area. Higher proportions of "Catholics" are in manual social classes. Differences between "Catholics" and "non-Catholics" in one or more age cohorts are observed for the following aspects of health and physical development: general and physical health (self-assessed health, number of symptoms, accidents), psychological distress (depression, anxiety, number of psychosomatic symptoms), impairments and disabilities (sight, hearing, wearing dentures, disability), and physical measures (height, waist-to-hip ratio, lung function). Furthermore, for all aspects except hearing, wearing dentures and number of psychosomatic symptoms, significant differences remain after accounting for sex and social class. For each measure where a difference is observed, it is those respondents with a Catholic parent or who were born Catholic who experience poorer health or physical development. This suggests that those of Irish Catholic descent are at some disadvantage compared with the rest of the population, with respect to health as well as social class, 150 years after the start of the main migration.

Adolescent↗
PubMed1997

Generational changes in height and body mass differences between British Asians and the general population in Glasgow.

A weighted total of 630 pupils aged 14-15 in Glasgow schools, about evenly divided between pupils of South Asian and non-Asian (overwhelmingly British) background, were measured for height and weight and compared with previous results for a similar Glasgow sample aged 30-40. Among 14-15-year-olds, British Asians were not so short compared with non-Asians as among 30-40-year-olds, especially females. Among 30-40-year-old Glasgow Asians only 7% were born in the UK, while among 14-15-year-old Glasgow Asians 86% were so born, indicating that they are the children of migrants. Generational differences in these comparisons cannot be due to positive selection of the migrant generation for height, and are attributed to improved environment, including nutrition and public health measures. This suggests the possibility of corresponding improvements in coronary and diabetic risk.

Adolescent↗
PubMed1997

Psychological distress among British South Asians: the contribution of stressful situations and subcultural differences in the West of Scotland Twenty-07 Study.

BACKGROUND: This paper seeks to explain an excess of psychological distress previously found among groups of British South Asians (with ancestry from the Indian subcontinent) living in Glasgow, compared with the general population. The excess was found on a psychosomatic measure and a measure of self-assessed distress but not on a clinically validated measure (the General Health Questionnaire or GHQ). The paper investigates whether South Asians are subject to stressful situations to which the GHQ is less sensitive than the other two measures. METHODS: Random samples of 159 South Asians aged 30-40, mean age 35, and 319 from the general population, all aged 35, were interviewed in Glasgow, using the 12-item General Health Questionnaire (GHQ-12), a psychosomatic symptom scale (PSS) and a self-assessment of distress. Subcultural groupings were differentiated by South Asian origin, English fluency, religion, and gender. Stressful situations assessed were experience of assault, stress/dissatisfaction with work, overcrowding, low standard of living, absence of family and absence of confidants. RESULTS: The GHQ-12 was less sensitive to certain stressful situations than the other two measures. The PSS and/or self-assessed distress were more sensitive to low standard of living, self-rated stress in work around the house and possibly experience of assault. In a combined analysis, the relation between distress on the PSS or self-assessed measure and subcultural groupings became nonsignificant, while the relation between distress and key stressful situations remained significant. CONCLUSIONS: The greater distress of women, Muslims and limited English speakers is largely explained by the stressful situations they experience. The GHQ-12 under-estimates distress related to situations experienced particularly by ethnic minorities and by women.

Adult↗
PubMed1997

Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure.

Defects in superoxide and hydrogen peroxide production may be implicated in the high incidence of bacterial infections in patients with acute liver failure (ALF). In the present study, oxygen radical production in patients with ALF due to paracetamol overdose was compared with that of healthy volunteers. Neutrophils from 14 ALF patients were stimulated via the complement receptors using zymosan opsonized with ALF or control serum. Superoxide and hydrogen peroxide production by ALF neutrophils stimulated with zymosan opsonized with ALF serum was significantly reduced compared with the control subjects (P < 0.01). This defect persisted when zymosan opsonized by control serum was used (P < 0.05). Superoxide and hydrogen peroxide production in neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP) from a further 18 ALF patients was unaffected compared with control neutrophils. Serum C3 complement levels were significantly reduced in ALF patients compared with control subjects (P < 0.0005). These results demonstrate a neutrophil defect in ALF due to paracetamol overdose, that is complement dependent but independent of serum complement, possibly connected to the complement receptor.

Acetaminophen↗
PubMed1997

Variations of hepatitis B virus core gene sequence in Western patients with chronic hepatitis B virus infection.

Heterogeneity of the hepatitis B virus (HBV) core gene has been reported to be associated with the presence of active liver disease in Japanese patients with chronic HBV infection. This study evaluated the significance of HBV core gene heterogeneity in Western patients with chronic HBV infection. The hepatitis B virus precore/core gene from 45 patients (inactive:active liver disease ratio 16:29) was amplified from serum by polymerase chain reaction (PCR). Gel electrophoresis was employed to detect large deletions. The PCR amplicons from 13 patients (all HBV serotype adw but with a different spectrum of liver disease) were cloned and sequenced. Hepatitis B surface antigen (HBsAg) serotypes were tested by enzyme immunoassay (EIA) and hepatic expression of HBV antigens was assessed by immunohistochemistry. The HBV core gene was amplified from the serum of all 45 patients. Three patients had mixed infection with both precore mutant and wild-type HBV and all three had active liver disease. No patient had a large deletion of the HBV core gene. Hepatitis B virus core gene sequence variations were more common in the midcore region and there was no difference in the number of silent and missense substitutions between those with inactive and active liver disease. There was no correlation between the nucleotide or encoded amino acid substitutions and the clinical and biochemical parameters, including the subsequent response to interferon-alpha therapy (n = 37) or hepatic HBV antigen expression. Variation of the HBV core gene was not found to be preferentially associated with active liver disease in Western patients with chronic HBV infection. The pattern of hepatitis B core gene variation is in accord with the genomic organization of HBV.

Adult↗
PubMed1997

Production of consistent crush lesions of murine skeletal muscle in vivo using an electromechanical device.

The crush model of injury in skeletal muscle is widely used in the investigation of tissue degeneration and regeneration. Previously, such trauma has been induced by using forceps to crush the muscle, commonly applying sufficient pressure to bring the mid-arms of the forceps together. This report introduces a reliable electromechanical device designed to generate reproducible focal lesions in skeletal muscle of mice. The tibialis anterior was crushed in 17 young adult mice. Two days after injury, the muscles were examined microscopically. By morphometric analysis, it was determined that the volumes of the lesions produced were similar (mean 0.499 mm3 +/- 0.098, range 0.278 - 0.601 mm3), and that the full extent of the damaged muscle was easily distinguished and readily quantifiable. This will allow a more precise comparison in future investigations into regenerative differences between age groups, satellite cell activation and the inflammatory response.

Animals↗
PubMed1997

Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis.

BACKGROUND & AIMS: In a recent study, we suggested that susceptibility to type 1 autoimmune hepatitis is associated with a six-amino acid motif, LLEQKR, within the DR beta polypeptide, but these data are in conflict with contemporary reports from Japan and Argentina. The purpose of the present study was to reexamine this question in a large independent cohort of patients. METHODS: Eighty-six North American white patients and 102 control subjects were studied. HLA class I antigens were determined serologically, and the DRB1, DQA1, DQB1, and DPB1 genes and the DRB3/4/5 subtypes were determined by high-resolution genotyping. RESULTS: The greatest risk was associated with DRB1*0301 (corrected probability [Pc] = 0.00003; relative risk [RR] = 4.58), and a secondary association with DRB1*0401 was identified (Pc = 0.000132; RR = 5.97). Protection from disease was associated with the DRB5*0101-DRB1*1501 haplotype (Pc = 0.021; RR = 0.3). However, further analysis indicated that a lysine residue at position 71 of the DR beta polypeptide may be the most important determinant of disease susceptibility (P = 0.0000003; RR = 8.6, increasing to RR = 16.38 with four lysine residues). CONCLUSIONS: DRB1*0301 and DRB1*0401 are confirmed as the principal susceptibility alleles for type 1 autoimmune hepatitis, and these data support the hypothesis that a lysine residue at position 71 of the DR beta-polypeptide chain may be the major risk factor.

Adult↗
PubMed1997

Growth hormone therapy in patients with cirrhosis: a pilot study of efficacy and safety.

BACKGROUND & AIMS: The protein catabolic state of cirrhosis is associated with severe growth hormone (GH) resistance, with low levels of insulin-like growth factor (IGF)-I and its major binding protein (IGFBP)-3. The aim of this study was to conduct a randomized, double-blind, placebo-controlled pilot study of GH therapy in 20 cirrhotic patients to assess the reversibility of GH resistance and subsequent impact on protein economy and safety. METHODS: Patients were treated with GH (0.25 IU/kg body wt) or placebo for 7 days. Serum levels of GH, IGF-I, IGFBP-3, and insulin were measured by radioimmunoassay and 24-hour urinary nitrogen by the Kjeldahl technique. RESULTS: IGF-I levels increased only in the GH-treated group (mean, 69.2 +/- SE 7.0 to 170.6 +/- 48.8 ng/mL; P < 0.05) together with IGFBP-3 (1.65 +/- 0.3 to 2.94 +/- 0.6 mg/L; P < 0.005). Cumulative nitrogen balance similarly improved only in the GH group (2.87-24.16 g; P < 0.05). No significant side effects of GH were observed. CONCLUSIONS: GH therapy can overcome the GH resistance of cirrhosis. The resulting improvement in nitrogen economy and possible influences on clinical outcomes will need to be confirmed in controlled studies of longer duration.

Aged↗
PubMed1997

Genetic linkage analysis of a variant of juvenile onset neuronal ceroid lipofuscinosis with granular osmiophilic deposits.

A number of variant forms of the neuronal ceroid lipofuscinoses (NCL) have been described and remain unmapped. The genes for infantile (CLN1), juvenile (CLN3) and Finnish-variant late-infantile (CLN5) have previously been mapped to chromosome regions 1p32, 16p12 and 13q21.1-32 respectively. The locus for a variant form of juvenile onset NCL characterised by cytosomal granular osmiophilic deposits (GROD) has been excluded from the CLN3 region of chromosome 16. This study describes the outcome of genetic linkage analysis in four families with this variant at the loci for the CLN1 and CLN5 genes. Using highly informative microsatellite markers tightly linked to the CLN5 locus we have excluded the JNCL variant with GROD from this region. Marker typing across the CLN1 region suggests that JNCL with GROD may be an allelic variant of infantile NCL.

Adolescent↗
PubMed1997

Dietary practices among Europeans and different South Asian groups in Coventry.

The dietary customs of people of South Asian origin living in Britain are important determinants of health but have been relatively little studied. As part of the Coventry study of diabetes carried out in the Foleshill ward of the city, subjects undergoing oral glucose tolerance tests provided information on this aspect of lifestyle. A questionnaire was completed by all of the last 612 subjects undergoing testing. These included 304 of European origin, 118 Punjabi Sikhs, seventy-six Pakistani/Punjabi Moslems, twenty-eight Gujerati Moslems, twenty-five Punjabi Hindus and forty-seven Gujerati Hindus. There were no discernible differences in the dietary customs of those with normal glucose tolerance, impaired glucose tolerance and newly diagnosed diabetes. Subjects of South Asian origin ate significantly fewer meals per day than European subjects. Evening meal times were 2-3 h later among South Asians. Europeans ate less fruit but more vegetables and more brown rice than South Asians. Gujeratis ate more rice, fried snacks and white flour. Moslems were least likely to be vegetarians, to drink alcohol and to use home-made ghee and yoghurt, and Punjabi Sikhs and Hindus ate dhal more frequently than Pakistani Moslems, Gujerati Moslems or Hindus. Most South Asians ate Indian sweets and 'Western' snacks.

Adult↗