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R Williams

Publications and source records attributed to R Williams.

At least 37 records · Page 2Linked to original sources
PubMed2002

Review article: the molecular adsorbents recirculating system (MARS) in liver failure.

In recent years different artificial liver support systems are being developed for use in patients with acute decompensation of chronic liver disease or acute liver failure. The molecular adsorbents recirculating system (MARS), a device in which patient's blood is dialysed across an albumin-impregnated membrane against a recirculated albumin-containing solution, seems to be effective in removing albumin-bound toxins, such as fatty acids, bile acids and bilirubin. Although the clinical experience with MARS is scarce, some pilot studies have reported its effectiveness at improving liver function and hepatic encephalopathy in patients with acute decompensation of chronic liver disease, and renal function in patients with hepatorenal syndrome type I. Data regarding MARS experience in acute liver failure and in primary graft dysfunction are encouraging but limited. Its real usefulness in these settings is, at present, under evaluation in randomized controlled clinical trials.

Humans↗
PubMed2002

The effect of thermocycling on five adhesive luting cements.

The importance of bond strengths between dental luting cements and dental restorative materials has become increasingly important as a result of the adhesive technologies that have been developed over recent years. This study investigated the effect on tensile bond strength at the metal to cement interface for a semiprecious alloy for different prepared surfaces, cements and ageing regimes. At 24 h following preparation, silicoating and C & B Metabond appear to have distinct advantages in terms of interfacial bond strength, which was also noted after storage for 7 days in buffered saline. After thermocycling only silicoating conferred greater interfacial tensile strength, and any advantage that the 4-Methacryloxyethyltrimellitic anhydride (4-META) chemistry may have had at 24 h was no longer apparent. The poorest performing cement regardless of the ageing regime was Aquacem, although in relative terms its performance improved after 24 h. This preliminary investigation indicated that in vitro environmental ageing including thermocycling erodes the claimed advantages of some more novel dental adhesives. This may have important clinical consequences in their usage, although it must be appreciated that current thermocycling methodology may not be an accurate predictor of in vivo performance.

Acrylic Resins↗
PubMed2002

Multi-disciplinary working in a forensic mental health setting: ethical codes of reference.

This paper reports on a small research project on multidisciplinary team-working within a medium secure forensic unit in the United Kingdom. Although multidisciplinary team working is widely accepted as an effective strategy for the delivery of healthcare services in modern society it is also recognized that interdisciplinary problems can also occur. This study developed two questionnaires, one being delivered to a number of groups and teams in the secure unit, whilst the second one was geared to individuals. A thematic analysis was employed to develop category building and concept formation. The results highlighted a three-level ethical code referencing system that was employed by both individuals and groups. Within this, three domains, or trajectories, were identified that were polarized continuums of main tensions for multidisciplinary staff working in forensic practice.

Clinical Competence↗
PubMed2002

Association of British Clinical Diabetologists (ABCD) survey of secondary care services for diabetes in the UK, 2000. 1. Methods and major findings.

OBJECTIVE: To examine the provision, and variations in, secondary care diabetes services in the UK. METHODOLOGY AND PARTICIPANTS: A postal survey of all 238 identified secondary care providers of diabetes services in 2000. RESULTS: Following two reminders, a 77% response rate was achieved. Major deficiencies in core staffing levels were recorded, with 36% of services provided by only one consultant physician with an interest in diabetes. The provision of diabetes specialist nurses was less than recommended in 87% of responses, whereas podiatry and dietetic support was unavailable in 3% and 27% of responses, respectively. Diabetes registers were not present in 28%, and a co-ordinated retinopathy screening programme unavailable in 26% of responses. Key biochemical measurements were unavailable in 9% (microalbuminuria) to 18% (HDL-cholesterol) of responses. A 'Well-Resourced Service' score was devised taking account of levels of personnel, facilities and specialized clinical services. There was a significant geographical variation in this score (P < 0.001), with the lowest score (least well-resourced services) in the Eastern NHS Region of England, and the highest score in the North-west NHS Region of England. The 'Well-Resourced Service' score was also significantly lower (P < 0.05) where there were less than two whole-time consultant physicians providing diabetes services. In contrast to other aspects of service provision, availability of dieticians and a combined diabetes-ophthalmology service had declined since 1990. Of 245 recorded bids for resources and service improvements for diabetes care, the success rate overall was 44%, and lowest where bids were made for dietetic and podiatry support. CONCLUSIONS: There is presently a major shortfall in provision of secondary care diabetes services throughout the UK, with evidence that there is significant regional variation and less facilities and resources where there are less than two consultants providing specialized diabetes services. On average bids for service improvements were only successful in < 50% of cases, most usually where the service was relatively better provided for. Considerable development and investment are required nationally to ensure equitable access to specialized diabetes services, a vital component in reducing adverse diabetes outcomes.

Delivery of Health Care↗
PubMed2002

Intussusception in an adult patient with severe hyperglycaemia--a case report.

AIMS: To report a case of adult intussusception associated with and possibly induced by acute hyperglycaemia. METHODS: We present the first case report of adult intussusception with severe hyperglycaemia. Clinical and laboratory data together with radiological findings are presented with a brief review of the literature. RESULTS: A 20-year-old man with no past medical history presented with abdominal pain for 2 days. The patient was severely hyperglycaemic with blood glucose of 72.7 mmol/l (normal 3.3-6.1 mmol/l), a pH of 7.2 and serum potassium of 6.5 mmol/l (normal 3.5-5.0 mmol/l). He had a computed tomography (CT) scan of the abdomen that revealed small bowel intussusception. Upon treatment of his hyperglycaemia, the patient's abdominal pain completely resolved. Follow up abdominal CT revealed complete resolution of the previously detected intussusception. CONCLUSION: Clinicians should be aware of the potential for the occurrence of intussusception in severely hyperglycaemic patients. Correction of hyperglycaemia could lead to resolution of the intussusception without surgical intervention. Possible effects of hyperkalaemia and/or acidosis on gastrointestinal motility should also be considered.

Abdominal Pain↗
PubMed2002

Esophageal pneumatic dilation for postfundoplication dysphagia: safety, efficacy, and predictors of outcome.

OBJECTIVE: Persistent dysphagia occurs in 5-10% of patients after fundoplication. The cause is obscure in most cases, and the management has not been well established. The aim of this study is to evaluate the clinical outcomes and the predictors of success for esophageal pneumatic dilations in patients with dysphagia after fundoplication. METHODS: We retrospectively reviewed 14 patients who underwent pneumatic dilation for persistent postfundoplication dysphagia. All patients had esophageal manometry before dilations. RESULTS: There were nine responders to pneumatic dilations (30-40-mm balloons). The nadir lower esophageal sphincter (LES) relaxation pressure was the only significant predictor for successful dilation and was higher among the responders than nonresponders (median 10 mm Hg vs 5 mm Hg). All six of 14 patients with nadir LES pressure > or = 10 mm Hg had a good response. There was no significant difference in the LES basal pressure between the responders and nonresponders (median 20 mm Hg vs 12 mm Hg). The median distal peristaltic amplitude (74 mm Hg vs 69 mm Hg), percent of failed peristalsis (8% vs 45%), and ramp pressure (19 mm Hg vs 17 mm Hg) did not differ significantly between the responders and nonresponders. No perforations occurred. CONCLUSIONS: Pneumatic dilation is a reasonably safe and effective treatment for patients with postfundoplication dysphagia. Raised nadir LES relaxation pressure seems to be a useful predictor of successful outcome.

Aged↗
PubMed2002

Effect of margins of excision on recurrence after local excision of ductal carcinoma in situ of the breast.

AIMS: To determine important factors influencing recurrence after local excision of duct carcinoma in situ (DCIS) of the breast. MATERIALS AND METHODS: The extent (size) in millimetres, classification (by cytonuclear grade (NHSBSP system), by extent of necrosis, and by the Van Nuys system), and excision margins of 115 cases of screen detected DCIS treated by local excision were measured. A prognostic index was calculated by the addition of the Van Nuys classification (low grade, 1; moderate grade, 2; high grade, 3), margin score (> or = 10 mm, 1; 1-9 mm, 2; < 1 mm, 3), and size score (< or = 15 mm, 1; 16-40 mm, 2; and > or = 41 mm, 3), giving a total score of 3-9. RESULTS: Classification using cytonuclear grade, extent of necrosis, or the Van Nuys system did not correlate significantly with recurrence. The excision margin (in millimetres) was associated with recurrence (p = 0.027) and if excision margin status was simplified using the scoring system (> or = 10 mm, 1; 1-9 mm, 2; < 1 mm, 3), the margin score was significantly associated with recurrence (p = 0.03). A prognostic index based on the Van Nuys score, margin status, and size was significantly associated with recurrence (p = 0.003). CONCLUSION: The results support the hypothesis that the margin of excision is the most important factor predicting the recurrence of DCIS after local excision.

Aged↗
PubMed2002

Antibiotic resistant tuberculosis in the United Kingdom: 1993-1999.

BACKGROUND: The re-emergence of tuberculosis as a global health problem over the past two decades, accompanied by an increase in tuberculosis drug resistance, prompted the development of a comprehensive national surveillance system for tuberculosis drug resistance in 1993. METHODS: The UK Mycobacterial Resistance Network (Mycobnet), which includes all mycobacterial reference and regional laboratories in the UK, collects a minimum dataset on all individuals from whom an initial isolate of Mycobacterium tuberculosis complex has been isolated and submitted by source hospital laboratories. Data sought include susceptibility to first line antibiotics, demographic, geographical, and risk factor information. RESULTS: There were 25 217 reports of initial isolates of M tuberculosis complex in the UK between 1993 and 1999. All were tested for sensitivity to isoniazid, rifampicin, and ethambutol and 12 692 of the isolates were also tested for sensitivity to pyrazinamide and streptomycin. A total of 1523 (6.1%) isolates were resistant to one or more drugs, 1397 isolates (5.6%) were resistant to isoniazid with or without resistance to other drugs, and 299 (1.2%) were multidrug resistant. Although the numbers of drug resistant isolates increased over the period, the proportions remained little changed. Certain groups of people were at a higher risk of acquiring drug resistant tuberculosis including younger men, residents of London, foreign born subjects, patients with a previous history of tuberculosis and those infected with HIV. CONCLUSION: Although the proportion of drug resistant tuberculosis cases appears to be stable in the UK at present, more than one in 20 patients has drug resistant disease at diagnosis and more than one in 100 has multidrug resistant disease. Tuberculosis control measures should be strengthened to minimise the emergence of drug resistance through rapid diagnosis, rapid identification of drug resistance, supervised treatment, and maintenance of comprehensive surveillance.

AIDS-Related Opportunistic Infections↗
PubMed2001

The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer.

LMO4 belongs to a family of LIM-only transcriptional regulators, the first two members of which are oncoproteins in acute T cell leukemia. We have explored a role for LMO4, initially described as a human breast tumor autoantigen, in developing mammary epithelium and breast oncogenesis. Lmo4 was expressed predominantly in the lobuloalveoli of the mammary gland during pregnancy. Consistent with a role in proliferation, forced expression of this gene inhibited differentiation of mammary epithelial cells. Overexpression of LMO4 mRNA was observed in 5 of 10 human breast cancer cell lines. Moreover, in situ hybridization analysis of 177 primary invasive breast carcinomas revealed overexpression of LMO4 in 56% of specimens. Immunohistochemistry confirmed overexpression in a high percentage (62%) of tumors. These studies imply a role for LMO4 in maintaining proliferation of mammary epithelium and suggest that deregulation of this gene may contribute to breast tumorigenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Liver transplantation in adults coinfected with HIV.

OBJECTIVE: To report our experience of prospectively identifying and transplanting livers into HIV-positive patients. DESIGN: Liver transplantation in HIV-positive patients remains controversial. The finding of HIV is usually considered a contraindication to any form of transplantation. Previously reported cases are few and refer to patients who tested HIV positive after they had their liver transplantations or who seroconverted in the posttransplantation period. This is, to our knowledge, the only report of patients who were known to be HIV positive at the time of decision for listing for transplantation. METHODS: The medical records of five HIV-positive patients who received liver transplants in King's College Hospital, London, during a 5-year period (January 1995-December 1999) were reviewed. All five were known to be HIV positive at the time of listing for liver replacement. Three of them had end-stage liver disease due to hepatitis C (two of them had underlying Hemophilia A) while the other two had acute liver failure, one due to hepatitis B infection and one due to nonA-nonB-nonC hepatitis. In all but one patient the HIV infection had been asymptomatic. RESULTS: All patients survived the immediate posttransplantation period, but the three patients with hepatitis C died of complications of recurrent hepatitis C between 6 and 25 months posttransplantation. The other two patients are currently alive 4 and 34 months posttransplantation with good graft function and without complications from their HIV infection. CONCLUSION: The early outcome of liver transplantation in HIV seropositive patients can be good, and patients should not be excluded from transplantation if their liver disease determines their prognosis. More effective antiviral therapy for hepatitis C given posttransplantation, and for hepatitis B reinfection, should improve the longer-term outcome of HIV patients with end-stage liver disease due to hepatitis.

Adolescent↗
PubMed2001

Trophoblast-specific expression and function of the integrin alpha 7 subunit in the peri-implantation mouse embryo.

For implantation and placentation to occur, mouse embryo trophoblast cells must penetrate the uterine stroma to make contact with maternal blood vessels. A major component of the uterine epithelial basement membrane and underlying stromal matrix with which they interact is the extracellular matrix protein laminin. We have identified integrin alpha 7 beta 1 as a major receptor for trophoblast-laminin interactions during implantation and yolk sac placenta formation. It is first expressed by trophectoderm cells of the late blastocyst and by all trophectoderm descendants in the early postimplantation embryo through E8.5, then disappears except in cells at the interface between the allantois and the ectoplacental plate. Integrin alpha 7 expression is a general characteristic of the early differentiation stages of rodent trophoblast, given that two different cultured trophoblast cell lines also express this integrin. Trophoblast cells interact with at least three different laminin isoforms (laminins 1, 2/4, and 10/11) in the blastocyst and in the uterus at the time of implantation. Outgrowth assays using function-blocking antibodies show that alpha 7 beta 1 is the major trophoblast receptor for laminin 1 and a functional receptor for laminins 2/4 and 10/11. When trophoblast cells are cultured on substrates of these three laminins, they attach and spread on all three, but show decreased proliferation on laminin 1. These results show that the alpha 7 beta 1 integrin is expressed by trophoblast cells and acts as receptor for several isoforms of laminin during implantation. These interactions are not only important for trophoblast adhesion and spreading but may also play a role in regulating trophectoderm proliferation and differentiation.

Alternative Splicing↗
PubMed2001

Comparative expressed sequence hybridization to chromosomes for tumor classification and identification of genomic regions of differential gene expression.

Altered expression of genes can have phenotypic consequences in cancer development and treatment, developmental abnormalities, and differentiation processes. Here we describe a rapid approach, termed comparative expressed sequence hybridization (CESH), which gives a genome-wide view of relative expression patterns within tissues according to chromosomal location. No prior knowledge of genes or cloning is required, and minimal amounts of tissue can be used. Expression profiles are achieved in a manner similar to the identification of chromosomal imbalances by comparative genomic hybridization analysis. The approach is demonstrated to indicate a chromosomal region that harbors overexpressed genes that may be associated with a drug-resistant phenotype. In addition, known and new regions of differential gene expression in both normal tissues and tumor samples from the soft tissue sarcoma group of rhabdomyosarcoma (RMS) are indicated. These regions included 2p24; overexpression of MYCN at 2p24 was confirmed by quantitative reverse transcription-PCR for all of the alveolar RMS cases and did not necessarily correspond to genomic amplification. Evidence including region specific microarray analysis indicated that overexpression of several genes from a region may be required for detection by CESH. This evidence is consistent with clusters of functionally related genes and mechanisms that affect the expression of a number of genes at a particular genomic location. The distinctive CESH profiles demonstrated in different subtypes of RMS show potential for tumor classification.

Chromosomes, Artificial, Yeast↗
PubMed2001

Hepatocyte Growth Factor/scatter factor-induces phosphorylation of cortactin in A431 cells in a Src kinase-independent manner.

The Hepatocyte Growth Factor receptor transduces proliferating and scattering signals in epithelial and endothelial cells. We have explored potential interactions of the HGF/SF receptor beta-subunit (p145(beta MET)) with F-actin binding partners aiming to identify novel downstream effectors implicated in HGF/SF pluripotent signalling. Cortactin, a p80/85 F-actin binding protein, was found phosphorylated on tyrosine in response to HGF-SF in A431 human epidermoid carcinoma cells, expressing the HGF/SF receptor (c-MET). The HGF/SF receptor was enriched in the detergent-insoluble fraction and was found to co-precipitate with cortactin and to associate in vitro with cortactin. The Grb2 small adapter protein known to associate via its Src homology 2 domain (SH2) with the MET C-terminus, was also associated with cortactin. Transient transfection of A431 cells with dominant-negative Grb2 constructs has revealed that the Grb2-C-SH3 domain possesses a central role in cortactin phosphorylation in response to HGF/SF. Finally, tyrosine phosphorylation of cortactin was found uncoupled of endogenous c-Src kinase activity, thus further supporting the hypothesis that cortactin is a direct target of the MET kinase. We propose that cortactin may constitute a docking site for MET-derived signals within the cytoskeleton.

Adaptor Proteins, Signal Transducing↗
PubMed2001

MUC 1: a genetic susceptibility to infertility?

In man and some animals regulation of embryo implantation by endometrial expression of the highly polymorphic MUC 1 mucin has been suggested. We assessed the polymorphism of MUC 1 in women known to be fertile and those with infertility due to suspected failure of embryo implantation. The median of the lower allele size in the infertile group was only 2.5 kb compared with 3.4 kb in the fertile group (p=0.0029, difference 0.9, [95% CI 0.1-1.3]). Women with unexplained infertility might have a genetic susceptibility to failure of embryo implantation due to small MUC 1 allele size.

Adult↗
PubMed2001

Global trends in resistance to antituberculosis drugs. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance.

BACKGROUND: Data on global trends in resistance to antituberculosis drugs are lacking. METHODS: We expanded the survey conducted by the World Health Organization and the International Union against Tuberculosis and Lung Disease to assess trends in resistance to antituberculosis drugs in countries on six continents. We obtained data using standard protocols from ongoing surveillance or from surveys of representative samples of all patients with tuberculosis. The standard sampling techniques distinguished between new and previously treated patients, and laboratory performance was checked by means of an international program of quality assurance. RESULTS: Between 1996 and 1999, patients in 58 geographic sites were surveyed; 28 sites provided data for at least two years. For patients with newly diagnosed tuberculosis, the frequency of resistance to at least one antituberculosis drug ranged from 1.7 percent in Uruguay to 36.9 percent in Estonia (median, 10.7 percent). The prevalence increased in Estonia, from 28.2 percent in 1994 to 36.9 percent in 1998 (P=0.01), and in Denmark, from 9.9 percent in 1995 to 13.1 percent in 1998 (P=0.04). The median prevalence of multidrug resistance among new cases of tuberculosis was only 1.0 percent, but the prevalence was much higherin Estonia (14.1 percent), Henan Province in China (10.8 percent), Latvia (9.0 percent), the Russian oblasts of Ivanovo (9.0 percent) and Tomsk (6.5 percent), Iran (5.0 percent), and Zhejiang Province in China (4.5 percent). There were significant decreases in multidrug resistance in France and the United States. In Estonia, the prevalence in all cases increased from 11.7 percent in 1994 to 18.1 percent in 1998 (P<0.001). CONCLUSIONS: Multidrug-resistant tuberculosis continues to be a serious problem, particularly among some countries of eastern Europe. Our survey also identified areas with a high prevalence of multidrug-resistant tuberculosis in such countries as China and Iran.

Antitubercular Agents↗
PubMed2001

Properties of microtubules assembled from mammalian tubulin synthesized in Escherichia coli.

When isolated from tissues, the alpha beta-dimeric protein tubulin consists of multiple isoforms which originate from the expression and subsequent posttranslational modification of multiple polypeptide sequences. Microtubules studied in vitro consist of mixtures of these isoforms. It is therefore not known whether dimers composed of single sequences of alpha- and beta-tubulin can polymerize to form microtubules, or whether posttranslational modifications may be necessary for microtubule assembly. To initiate investigation of these questions, rabbit reticulocyte lysate, which contains the cytoplasmic chaperonin CCT and its cofactors, was employed to prepare substantial quantities (tens of micrograms) of active tubulin by in vitro folding of mouse alpha- and beta-tubulins recombinantly synthesized in E. coli. This recombinant tubulin is composed of only a single alpha-chain and a single beta-chain. When analyzed after folding by isoelectric focusing, each chain yielded only one band, indicating that neither was detectably posttranslationally modified in the course of the folding reaction. When subjected to assembly-promoting conditions, this tubulin formed microtubules without the addition of any exogenous protein. Electron microscopy showed them to be of normal morphology. Analysis of their protein composition showed that they are composed nearly entirely of recombinant tubulin. These results demonstrate that the naturally occurring mixtures of isoforms are not strictly required for the formation of microtubules. They also open a route to other studies, both biomedical and structural, of fully defined tubulin in vitro.

Animals↗