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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 415 records · Page 23Linked to original sources
PubMed1996

A prospective randomised trial of bile duct reconstruction at liver transplantation: T tube or no T tube?

A prospective randomised study of end-to-end bile duct reconstruction with or without T-tube drainage during orthotopic liver transplantation (OLT) was undertaken in 60 patients well matched for age, sex, aetiology of liver disease, operative blood loss, cold ischaemic time, preoperative serum bilirubin level and Child-Pugh score. Significant biliary complications in the T tube group occurred in five patients and included bile duct stricture (n = 2), bile leak/peritonitis (n = 1) and cholangitis (n = 2). Bile duct strictures occurred in six patients in the no T tube group (P > 0.05, NS). Hepatic artery stenosis was identified in one patient from each group in association with a biliary stricture. Biliary complications in both groups were associated with a prolonged graft cold ischaemic time (P < 0.01). As no significant difference was noted in the number of early and late biliary complications between the two groups, the routine use of a T tube has been discontinued.

Adolescent↗
PubMed1996

Usefulness and limitation of phylogenetic analysis for hepatitis C virus core region: application to isolates from Egyptian and Yemeni patients.

We report here the nucleotide sequences of the core region of HCV isolates from Egyptian and Yemeni patients and the method for classifying these HCV isolates by phylogenetic analysis. Sequence comparison suggested that the genotypes of these isolates were the same. Preliminary phylogenetic analysis of the HCV core region indicated that the genotypes of both isolates were 1c. However, an additional phylogenetic tree of the HCV core region constructed using a greater number of HCV isolates than that used in the preliminary analysis and on the basis of alignment of nucleotide sequences in an appropriate length indicated that the genotypes of these isolates were 4 and not 1c. For a more detailed analysis, the nucleotide sequences of the HCV E1 region as well as the core region for the same Yemeni patient were determined. A phylogenetic tree of the E1 region confirmed that the genotype of the HCV isolate from the Yemeni patient was 4. These data indicate that even when classifying HCV isolates using phylogenetic analysis, the misclassification would occur if care is not taken regarding the number and sequence lengths of the isolates included in the analysis.

Base Sequence↗
PubMed1996

Ribosomal RNA location in the Antarctic fish Champsocephalus gunnari (Notothenioidei, Channichthyidae) using banding and fluorescence in situ hybridization.

A biotinylated 28S rDNA probe was prepared from the genomic DNA of the Antarctic ice-fish Champsocephalus gunnari and hybridized to metaphase chromosomes of the same species by fluorescence in situ hybridization (FISH). The hybridization signal appeared over the whole heterochromatic arm of the submetacentric chromosomes bearing the nucleolar organizer regions. The results of rDNA/FISH are compared with those coming from classical cytogenetic (C, Q, Ag-NOR, chromomycin A3) banding techniques. The in situ detection of a specific DNA sequence offers a new more precise perspective for understanding the evolving process in chromosomes of Antarctic fish and will provide an interesting contribution to comparative cytogenetics of lower vertebrates.

Animals↗
PubMed1996

Cortical plaques visualised by fluid-attenuated inversion recovery imaging in relapsing multiple sclerosis.

Fluid-attenuated inversion recovery (FLAIR) imaging with prolonged inversion times allows generation of highly T2-weighted images of the brain with suppression of cerebrospinal fluid signal. Such sequences result in high lesion contrast and allow visualisation of abnormalities not seen with conventional T2-weighted spin-echo sequences. We used FLAIR sequences, proton density (PD) and standard T2-weighted images to examine lesion number and distribution in ten patients with clinically definite relapsing multiple sclerosis (MS). We also studied the extent and distribution of blood-brain-barrier breakdown by gadolinium-enhanced T1-weighted images. FLAIR sequences proved feasible both in terms of acquisition time and image quality using a 0.5 T imager. FLAIR imaging allowed identification of 45% more high-signal lesions than T2-weighted or PD images in the 10 patients. In particular, 60% more lesions within the cortex and at the grey-white interface were identified. Cortical lesions, none of which enhanced following gadolinium-DTPA injection, were present in seven of the ten patients studied. Of all lesions identified, 8% were cortical. FLAIR sequences are more sensitive to cortical and subcortical lesions in patients with active demyelination.

Adult↗
PubMed1996

Chronic emotional processing in survivors of the Herald of Free Enterprise disaster: the relationship of intrusion and avoidance at 3 years to distress at 5 years.

Thirty-seven survivors completed the Impact of Event Scale (IES), a measure of intrusive and avoidant activity, at around 3 yr following the Herald of Free Enterprise disaster. The aim of the present study was to examine the relationship between scores on the IES to scores on the Beck Depression Inventory (BDI) and the Spielberger State Anxiety Inventory (STAI-Y1) at around 5 yr subsequent to the event. Higher scores on the IES were able to predict higher scores on the BDI and the STAI-Y1 over and above scores on the 28-item General Health Questionnaire (GHQ-28) which was also administered at around 3 yr on from the event. Implications for cognitive-behaviour therapy are discussed.

Adult↗
PubMed1996

Effect of flumazenil on the electroencephalogram of patients with portosystemic encephalopathy. Results of a double blind, randomised, placebo-controlled multicentre trial.

The efficacy of the benzodiazepine antagonist flumazenil has been assessed clinically in a double blind, randomised, placebo-controlled multicentre study in patients with grade I-III portosystemic encephalopathy. In an ancillary study reported here the effect of flumazenil on the electroencephalogram (EEG) was analysed in 32 patients who had EEG grading according to protocol. Following the baseline observation period, patients were randomised to receive (at 1 min interval) 3 sequential bolus injections of flumazenil (0.4, 0.8 and 1 mg) or placebo followed by infusions of flumazenil (1 mg/h) or placebo for 3 h. Patients were monitored for 5 h after infusion. A positive response was defined as 1 point improvement in EEG grade. After independent analysis of the EEG gradings 5 out of 17 (29%) flumazenil treated patients showed an improvement in EEG grading (3 after bolus, 2 during follow-up) compared to 2 out of 15 (13%) placebo treated patients (1 after bolus, 1 during follow-up) (95% confidence interval of difference: -12% to + 50%). Of the 5 EEG responders after flumazenil, 3 also had an improvement in clinical PSE grading (none after bolus, 2 during infusion, 1 during follow-up), compared to neither of the 2 EEG responders after placebo. EEg responders did not differ from non-responders with respect to Child-Pugh score, basal EEG, PSE grade and positivity for benzodiazepines. In conclusion, treatment perspectives for flumazenil in portosystemic encephalopathy appear to be present for only a minority of patients; however, this study yields no support for a major role of benzodiazepine antagonists in the treatment of hepatic encephalopathy.

Adult↗
PubMed1996

Expression of the Notch 3 intracellular domain in mouse central nervous system progenitor cells is lethal and leads to disturbed neural tube development.

Notch-like receptors are found in organisms ranging from nematodes to mammals. In Drosophila, Notch plays a key role in cell fate decisions in the early nervous system. In this report we analyse the effects of excess Notch 3 activity in central nervous system (CNS) progenitor cells. A mutated Notch gene encoding the intracellular domain of mouse Notch 3 transcribed from the nestin promoter was expressed in CNS progenitor cells in transgenic mice. This mutation resulted in a phenotypic series of neural tube defects in embryonic day 10.5-12.5 embryos and proved lethal to embryos beyond this age. In the milder phenotype the neural tube displayed a zig-zag morphology and the CNS was slightly enlarged. More severely affected embryos showed a lack of closure of the anterior neural pore, resulting in the externalization of neural tissue and the complete collapse of the third and fourth ventricles. The expanded ventricular zone of the neuroepithelium, a correspondingly enlarged area of nestin expression, and an increase in the number of proliferating cells in the neural tube suggested that these phenotypes resulted from an expanded CNS progenitor cell population. These data provide support in vivo for the notion that Notch activity plays a role in mammalian CNS development and may be required to guide CNS progenitor cells in their choice between continued proliferation or neuronal differentiation.

Animals↗
PubMed1996

Acquired sideroblastic anaemia induced by a copper-chelating agent.

Acquired sideroblastic anaemia may be related to drugs and other chemicals that inhibit the activity of mitochondrial enzymes involved in haem synthesis. We report a case of secondary acquired sideroblastic anaemia following administration of triethylene tetramine dihydrochloride (trientine), a second-line copper-chelating agent used in the treatment of Wilson's disease. The anaemia improved after dose reduction of trientine. The mechanism of induction of sideroblastic anaemia in this case is unclear, but trientine does not appear to alter the function of two key mitochondrial haem enzymes, and may instead act directly on mitochondrial iron metabolism.

Adolescent↗
PubMed1996

Managing osteopetrosis in children: a nutrition challenge.

Osteopetrosis, a rare condition caused by a failure of osteoclasts to resorb bone, results in dense and deformed bones, growth failure, anemia, hypoplastic dentition, chronic infection, blindness, and massive splenomegaly. Children with infantile osteopetrosis have disease-related complications that affect nutritional status. Altered calcium and phosphorus intake has been reported in these patients, but previous studies did not include an assessment of dietary adequacy or nutrition-related complications. A prospective study of six children with severe infantile osteopetrosis was conducted to identify specific nutrition-related problems and effective nutrition intervention strategies. Patients were monitored by a registered dietitian while they participated in a clinical research protocol at St Jude Children's Research Hospital. Dietary records for each patient were obtained at set intervals during the 4-month study period. Because most patients lacked adequate dentition, they had difficulty obtaining adequate nutrition through normal oral intake. Three children required nutrition supplementation (enteral feedings for one and oral supplements for two). We conclude that oral and enteral nutrition support can provide nutrients needed for improved growth and response to treatment in patients with osteopetrosis.

Adolescent↗
PubMed1996

Pseudotumours of hepatic imaging.

The diagnosis of liver tumours with CT depends on differential attenuation coefficients and enhancement patterns. The sensitivity of CT in defining tumours is well established but there remain a variety of conditions that mimic these patterns, presenting a 'pseudotumour' appearance. A common illustrative example is hepatic steatosis, but less well recorded are the sphingolipidoses and intrahepatic arterioportal shunts, either post-traumatic or related to venous outflow block. Alpha-1-antitrypsin deficiency and hereditary tyrosinaemia provide examples in childhood.

Adolescent↗
PubMed1996

Characterization of monoclonal antibodies raised to C-terminal peptides of pS2: a major trefoil peptide and motility factor expressed in adenocarcinomas and regions of mucosal injury.

Two novel monoclonal antibodies, GE1 and GE2 raised against the C-terminal 31 and 28 amino acids of the estrogen-inducible trefoil peptide pS2, are described. Both antibodies are able to detect pS2 in formalin-fixed, paraffin-embedded tissues. Conditions are presented under which pS2 can be shown in cell lines by immunohistochemistry that has previously been problematic. The antibodies can specifically show the presence of pS2 in cell lysates by Western blotting and immunoprecipitation. In the form of an affinity column, the GE1 monoclonal antibody can be used to purify pS2 from MCF-7 supernatants. The eluted peptide from the GE1 affinity column shows a single band at 6,600 Da (predicted size for pS2) on Western blotting. These antibodies are valuable reagents in the analysis of the role of trefoil peptides in the maintenance of mucosal integrity, and may have applications in the assessment of pS2 expression in chronic gastrointestinal ulceration and adenocarcinomas that secrete pS2, where it may serve as a prognostic marker.

Adenocarcinoma↗
PubMed1996

Peripheral blood and intrahepatic subsets of T lymphocyte activation and function in liver allograft rejection and drug-induced tolerance in rats.

T lymphocyte kinetics in liver allograft rejection were studied by measuring levels of activated (CD25+ and class II MHC+) T lymphocytes (CD5+) and T cell subsets (CD4 and CD8) in peripheral blood and the livers of allogeneic DA (RT1b) to LEW (RT1') and syngeneic LEW to LEW orthotopic rat liver transplants. Median survival was 10 days in untreated allogeneic rats (n = 17). Mean (+/- SEM) T lymphocyte class II MHC expression increased from 3.4 +/- 0.44% (day 2/3) to 4.9 +/- 1.1% (day 7) (p = 0.01). Complete sequential data were available for nine animals over the period of rejection confirming the increase in class II MHC expression (p = 0.05) and showing a decrease in CD25 expression (p = 0.05). There was a significant fall in CD4:CD8 ratio from day 2/3 to day 7 (p = 0.002). CD25 and class II MHC molecule expression and the CD4:CD8 ratio remained unchanged over the comparable period in the syngeneic LEW to LEW control model (n = 5, p > 0.3 for all comparisons). Cyclosporin A (5 mg/kg/day) was given orally for 17 days and then withdrawn to induce allograft tolerance in a further nine DA to LEW rats (median survival > 100 days). Samples taken at 2/3, 7, 17, 30, 40 and 100 days showed that T cell activation marker expression remained low during cyclosporin treatment (e.g. class II MHC expression 2.32 +/- 0.35%; CD25 expression 3.53 +/- 0.44% on day 7) but increased thereafter (e.g. class II MHC expression 8.19 +/- 0.65%. CD25 13.25 +/- 0.95% on day 100). There was a fall in CD4:CD8 ratio throughout (p < 0.001). Intrahepatic mononuclear cells were harvested from six normal livers, four allogeneic livers (at 10 days), five syngeneic livers (at 10 days) and five tolerant allografts (at 100 days). Rejecting grafts showed the highest proportion of T lymphocytes (66.8 +/- 4.0% vs 18.5 +/- 3.6% in controls, p = 0.01). T cell activation was higher in both rejecting and tolerant grafts versus normal control livers (p = 0.05 for CD25 and p < 0.01 for class II MHC expression). CD8+ lymphocytes predominated in the hepatic infiltrate in all models, although the majority of these cells were both CD5 and alpha beta T cell receptor negative. There was a higher proportion of T cells in tolerant allografts (44.5 +/- 5.2%, p < 0.01) compared with control animals. Serial changes in peripheral T lymphocyte subsets may be useful in monitoring experimental acute rejection. In peripheral blood, the increase in T cell activation and loss of CD4+ lymphocytes, along with evidence of increased intragraft infiltration by this subset implies that it has a primary role in the development of tolerance in this nodel.

Animals↗
PubMed1996

Plasma inhibitory activity against tumour necrosis factor in fulminant hepatic failure.

1. Soluble tumour necrosis factor receptors released into the circulation inhibit the effects of excess tumour necrosis factor-alpha and represent an important protective response. 2. In this study we have measured the levels of tumour necrosis factor and soluble tumour necrosis factor receptors p55 and p75 in the plasma of 10 patients with fulminant hepatic failure and 10 healthy control subjects. The capacity of the plasmas at varying dilutions to inhibit the biological activity of 1000 pg/ml of recombinant tumour necrosis factor in a tumour necrosis factor cytotoxicity assay in vitro was also determined. 3. The mean plasma levels of tumour necrosis factor in patients with fulminant hepatic failure (48.4 +/- 10.9 pg/ml) were significantly increased compared with normal control subjects (6.1 +/- 1.04 pg/ml, P < 0.01). Plasma soluble tumour necrosis factor receptors p55 and p75 were also significantly elevated in patients with fulminant hepatic failure (18.16 +/- 9.94 ng/ml and 16.06 +/- 9.93 ng/ml respectively) when compared with normal control subjects (1.28 +/- 0.24 ng/ml and 1.62 +/- 0.91 ng/ml, P < 0.001). 4. Fulminant hepatic failure plasma had a much lower capacity to inhibit tumour necrosis factor bioactivity in vitro, with a statistically significant difference between the inhibitory capacity of the fulminant hepatic failure and normal plasma seen at plasma dilutions of 1:5 and 1:20 (P < 0.05). 5. The reduced tumour necrosis factor neutralization capacity observed in fulminant hepatic failure, despite the increased levels of soluble tumour necrosis factor receptors, suggests enhanced susceptibility to the potential deleterious effects of tumour necrosis factor in fulminant hepatic failure.

Adolescent↗
PubMed1996

Irish descent, religion, and alcohol and tobacco use.

The West of Scotland has traditionally been a focus for Irish migration. Using data from two studies carried out in this region, one quantitative, the other qualitative, this paper shows little difference in drinking and smoking between Scots of Irish descent and other Scots. It does, however, show significant differences in these behaviours according to religious affiliation in adulthood. Rather than confirming the stereotype of Irish Catholics as heavy drinkers and smokers the present paper puts forward the hypothesis that drinkers and smokers are differentially retained in membership by different religious affiliations, and argues that this accounts for differences in reputation and in health-related behaviours.

Adolescent↗