Nutrition and liver transplantation.
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Humans↗
Biomedical subjects
R Williams
Publications and source records attributed to R Williams.
Tolerance after liver transplantation: does it exist and can immunosuppression be withdrawn?
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Humans↗
Thrombin is effective in arresting bleeding from gastric variceal hemorrhage.
Gastric variceal hemorrhage is associated with a high morbidity and mortality. We report the efficacy and safety of bovine thrombin in the treatment of bleeding gastric varices. At endoscopy 52 patients with hematemesis were diagnosed with bleeding gastric varices. Patients were treated by intravariceal injection with bovine thrombin and underwent further endoscopy at 72 hr and then at two-week intervals. Initial hemostasis was achieved in 49/52 patients (94%). Bleeding-related mortality at 72 hr after the index bleed was 3/52 (6%). The mean amount of thrombin used to achieve initial hemostasis was 1070 IU (range 400-2000 IU) and no adverse drug effects were observed. The median number of treatment sessions required to achieve gastric variceal ablation was 2 (range 1-3). At six weeks, 9 of 49 surviving patients (18%) rebled and one further patient died. The six-week mortality in patients treated with thrombin was 4/52 (8%). In conclusion, safe and effective hemostasis of bleeding gastric varices can be achieved by intravariceal injection with thrombin.
Adult↗
Development of a novel bi-specific monoclonal antibody approach for tumour targeting.
To overcome the disadvantages of bi-specific antibody methodologies in vivo, a novel antibody approach has been designed to improve tumour targeting and effector to target ratio. The technique involves biotinylated anti-CD3 Fab fragments and streptavidinylated anti-tumour monoclonal antibodies (mAbs) that can spontaneously form cross-links. We describe here a method for the direct cross-linking of sulphydryl-conjugated HMFG1 (anti-MUC1 mucin mAb) to streptavidin by sulphosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate. Fab fragments generated by papain digestion of the 1452C11 antibody (anti-CD3 mAb without Fc to avoid peripheral activation of T-cells) were biotinylated with NHS-Iminobiotin. MUC1-transfected BALB/c breast cancer cell lines 413BCR and 425CCR and the parental cell line (410.4) were labelled with streptavidinylated mouse anti-MUC1 mucin mAb. BALB/c effector T-cells were separately labelled with biotinylated anti-CD3 Fab fragments (1452C11) and mixed with tumour cells in different effector to target ratios. Percentage of killing was assessed using the 51Cr cytotoxicity assay. Seventy per cent lysis was measured in the case of 413BCR (high MUC1 mucin expressor) and 40% in the case of 425CCR (low expressor) cell line. No lysis was apparent in the MUC1 negative cell line. These results demonstrate that the novel T-cell redirecting approach we have developed can produce effective immune lysis of target cells in vitro.
Animals↗
Assessment of potential donors for living related liver transplantation.
BACKGROUND: Living related liver transplantation has been developed as an important potential source of organs for treatment of children with acute and chronic liver disease. A single UK centre performing living related liver transplantation was established in 1993. METHODS: Parents who were potential donors for their children for living related liver transplantation were assessed for suitability according to a protocol based on one developed and published by the University of Chicago Transplant Group. Records kept by the transplant coordinators were retrieved and data were extracted. RESULTS: Of 64 potential donors for 32 potential recipients ten were excluded at a preliminary stage. Fourteen ultimately became donors. Of 54 parents who began evaluation 23 were finally considered to be suitable. There were 19 non-disease-related reasons for unsuitability: blood group mismatch (eight cases), size discrepancy (six), pregnancy (two), oral contraceptive medication (one), vascular anatomy variant (one) and age (one). Sixteen were unsuitable because disease was found, namely fatty liver (four), thyroid disease (two), hepatitis B positivity (two), cardiac murmur (one), anaemia (one), glucose-6-phosphate dehydrogenase deficiency (one), diabetes mellitus (one) and psychological problems (one), and three parents were affected by the same disorder as the child (Alagille syndrome, one; mitochondrial disorder, one; recurrent cholestasis, one). Three parents were rejected for more than one reason. Both parents were unsuitable for donation in 21 per cent of cases. CONCLUSION: Parents approach living related liver transplantation with enthusiasm. They should be advised of the high chance of unsuitability, including the finding of significant pathology. The limitation of living related liver transplantation as the major source of organs for children is recognized.
Adolescent↗
Treatment of chronic hepatitis B virus infection: an Asia-Pacific perspective.
Chronic hepatitis B infection is a serious health threat in the Asia-Pacific area. A consensus meeting on the treatment of chronic hepatitis B infection was conducted in Hong Kong, in August 1997. It was generally agreed that treatment of chronic hepatitis B infection should be based on the understanding of the natural history of chronic hepatitis B infection. To date, interferon alpha is the only Food and Drug Administration (FDA)-approved form of therapy for chronic hepatitis B infection. The overall response in Asian patients is unsatisfactory: approximately 15-20% will clear hepatitis B e antigen, but less than 5% will clear hepatitis B surface antigen. Newer immunomodulatory therapies are under trial. In contrast, nucleoside analogues, such as lamivudine (pending FDA approval) and famciclovir, have been shown to be potent suppressors of hepatitis B viral replication; however, their role as monotherapy in the treatment of chronic hepatitis B infection remains to be defined. Also, the issues of resistance to nucleoside analogues and withdrawal rebound need to be carefully studied. The future direction of therapy in chronic hepatitis B infection is probably a combination of nucleoside analogues or nucleoside analogues with immunomodulatory therapy.
2-Aminopurine↗
Extracorporeal support and hepatocyte transplantation in acute liver failure and cirrhosis.
The relative shortage of donor organs and lack of immediate availability mean that many patients with acute liver failure die before orthotopic liver transplantation can be performed. An effective temporary liver support system could improve the chance of survival with or without a transplant being ultimately carried out. Recent technological advances resulting in improved maintenance of hepatocyte viability and function in culture and bioreactor designs which facilitate adequate perfusion of the cellular component and removal of products of cellular metabolism have led to the development of a number of bioartificial devices for liver support. Three such devices have undergone preliminary clinical evaluation in the setting of acute liver failure, with a statistically significant reduction in raised intracerebral pressure along with improvements in consciousness level and some biochemical parameters associated with treatment with one of these. Several other devices with different characteristics have shown promise in vitro and/or in animal models but await clinical evaluation. Several new totally artificial systems have also been described, along with the emergence of isolated hepatocyte transplantation, with reports of successful 'bridging' to liver transplantation. Controlled trials on a multicentre basis in well-defined patient groups and with standardized outcome measures will be required to properly evaluate the clinical value of each of these approaches to providing liver support in acute liver failure and cirrhosis. A better understanding of mechanisms underlying multiorgan failure and of factors inhibiting liver regeneration, thereby allowing a more targeted approach, will be essential to the further development of effective liver support strategies in these settings.
Animals↗
Movement-related variation in forces under compression stockings.
OBJECTIVES: Compression therapy is widely used in the treatment of venous leg ulcers, but the efficacy of this treatment is variable. Assessment of variation in compression forces associated with movement may help to elucidate the mechanism of action of compression therapy. The aim of this study was to develop and apply a system to investigate forces under compression stockings during movement. METHOD: Three sensors were placed on the medial aspect of the left leg on six healthy volunteers to monitor forces under class 2 (Continental European classification) compression stockings. Data were recorded during dorsiflexion and plantar flexion of the left foot and also during short periods of walking. RESULTS: Changes in pressure were observed, associated with dorsiflexion and plantar flexion of the foot. These changes were dependent on sensor position. Changes in pressure during walking were also position-dependent and of variable duration. CONCLUSIONS: The system enables forces associated with compression therapy to be examined during movement and may thus be of value in further understanding its mechanism of action. Foot movement can be associated with clear changes in pressure under compression stockings and rapid changes in pressure may occur during walking.
Adult↗
Morbidity and Irish Catholic descent in Britain: relating health disadvantage to behaviour.
OBJECTIVES: This paper critically evaluates the evidence for two health-related stereotypes of the Irish, namely that behaviours such as smoking and heavy drinking explain their excess morbidity in Britain, and secondly that, in illness, this ethnic group behaves more stoically. DESIGN: Data are reported on over 850 respondents from each of three cohorts (aged 18, 39 and 58 in 1990/91) of the West of Scotland 20-07 Study, in which a small but pervasive excess of morbidity has been observed in those of Catholic background (in this area associated with Irish descent). Logistic regression was used to investigate any differences in drinking, smoking and participation in sport between those of Catholic and non-Catholic heritage, whilst controlling for sex and social class. Where a difference was observed, we looked for an association between health-related behaviour and the Catholic morbidity excess for six measures of physical and mental health. Finally, illness behaviour at age 39 and 58 was investigated for those experiencing one of a number of common symptoms in the month prior to interview, by noting whether a general medical practitioner (GP) was consulted. RESULTS: The only difference in health-related behaviour was in the eldest cohort, where an excess of smoking was observed for the Catholics. However, except for lung power, smoking was not able to explain very much, if any, of the Catholic morbidity disadvantage. For most of the symptoms studied, GP consultation rates were similar, although there was a tendency towards Catholic over-consulting. CONCLUSION: This paper finds minimal evidence in favour of either stereotype: behaviours such as smoking and excess drinking were not strongly associated with the poor morbidity status of the Irish in the population we have studied; neither have the Irish been found to be more stoic in illness. Therefore the stereotypes are not an adequate explanation, nor a necessary correlate, of the frequent finding of raised morbidity in communities of Irish Catholic origin.
Adolescent↗
Individuals with low back pain: how do they view physical activity?
BACKGROUND: Recent guidelines for those with acute low back pain have advocated early resumption of normal activity and increased physical activity. Little is known about the relationship between low back pain and physical activity, and on the impact of that relationship on the promotion of increased levels of physical activity within a general practice population. OBJECTIVES: We aimed to explore associations between factors that influence changes in physical activity and the way individuals perceive and behave with their low back pain, and the impact of those perceptions and behaviour on physical activity. METHODS: Twenty-seven informants were chosen using a purposive sample from a larger group of individuals who, because of their low back trouble, had been referred by their GPs to a community-based, single-blind, randomized controlled trial (RCT) at the University of York, which is evaluating the effectiveness and cost-effectiveness of a progressive exercise programme. Fifty-four interviews were conducted with this subgroup of the RCT; four informants were interviewed once, 19 twice and four of them three times. Interviews were transcribed and analysed using manual and computer-aided approaches. RESULTS: Physical activity was perceived as (i) activities of daily living, (ii) activities causing breathlessness that they went out of the way to do and (iii) more competitive-type activity. The avoidance of physical activity and fear of pain returning were the two main factors directly associated with informants' backs and changes in physical activity. These two factors hindered increases in physical activity, even though the majority of informants believed strongly that being physically active helped ease their low back pain. CONCLUSIONS: When advocating that individuals with acute low back pain return to or increase physical activity, it is important that clinicians identify avoidance of physical activity and/or fear of pain at the earliest stage in order to tailor advice and reassurance appropriately. If avoidance of activity and fear of pain is identified and clinicians want to encourage patients to take up and sustain increased physical activity, they should explore issues of fear of pain, and avoidance of and confidence to do physical activities, in addition to other factors influencing physical activity.
Adult↗
Association of medical, physiological, behavioural and socio-economic factors with elevated mortality in men of Irish heritage in West Scotland.
BACKGROUND: Men with patrilineal Irish descent from the immigrations of the nineteenth and twentieth centuries have higher death rates from 'all-causes' and, specifically, cardiovascular disease (CVD) than the general population of the West of Scotland. METHODS: A total of 5766 male employees from 27 workplace settings were examined between 1970 and 1973. Surname analysis identified 15 per cent of these men as of patrilineal Irish heritage. For those who have since died, the date and cause of death was obtained. Cox's proportional hazards model was used to compare the mortality risk of those with Irish and non-Irish surnames, and to investigate established medical, physiological, behavioural and socio-economic risk factors (acting in early and later life) as possible explanations for this excess mortality. RESULTS: The relative risk of death from all causes for the Irish of 1.26 (95 per cent confidence interval (CI) (1.12, 1.43)) was reduced to 1.12 (95 per cent CI (0.99, 1.26)) by including established risk factors in the model. The relative risk of CVD mortality of 1.51 (95 per cent CI (1.29, 1.77)) for the Irish was reduced to 1.35 (95 per cent CI (1.14, 1.58)) by the same adjustments. The elevated all-cause mortality of the Irish was mainly attributable to cardiovascular deaths. CONCLUSIONS: Cigarette smoking was only able to 'explain' a small amount of the excess all-cause and CVD mortality of men with patrilineal Irish descent. Relative deprivation during childhood and adulthood contributed to the high Irish mortality. However, there remains a substantial excess of premature deaths among Irish men which is unaccounted for by established risk factors.
Adult↗
Non-invasive assessment of bone density in primary biliary cirrhosis.
BACKGROUND/AIMS: Low bone mass is an important complication of primary biliary cirrhosis (PBC), resulting in an increased risk of fractures and reduced mobility. In the present study, we sought to determine the frequency of low bone mass in PBC, and its relationship to disease severity and non-invasive markers of bone turnover. METHODS: In 36 women with PBC, bone mineral density of the lumbar spine and hip was assessed by dual emission X-ray absorptiometry. Serum and urinary markers of bone turnover were compared with those from age- and sex-matched controls. RESULTS: Spinal osteopenia (T score, -1.5 to -2.5) was present in 15 of the 36 patients (42%), while six others (16%) had established osteoporosis (T < -2.5). Osteopenia of the femoral neck was found in 17 patients (47%), and osteoporosis in five (14%). The severity of liver disease, as determined by Mayo Clinic R score and histological stage, correlated negatively with both regional bone mineral density and total bone mineral content expressed as a ratio to lean body mass. There was a strong positive correlation between serum levels of the procollagen degradation peptides, PICP and PIIINP (r = 0.65, P < 0.001), and both peptides correlated significantly (P < 0.001) with histological stage and Mayo Clinic R score. Fasting urinary pyridinoline and deoxypyridinoline to creatinine ratios were also significantly raised. CONCLUSIONS: Low bone mass in PBC correlates positively with disease severity, and is associated with a net increase in bone resorption, as assessed by urinary collagen cross-link excretion. These markers of bone turnover may be of value in controlled clinical trials aimed at improving bone mass in PBC.
Absorptiometry, Photon↗
Cultural safety--what does it mean for our work practice?
Culturally safe service delivery is critical in enhancing personal empowerment and, as a result, should promote more effective and meaningful pathways to self determination for Indigenous people. Little has been said about encouraging people from Indigenous groups into the health and education discipline(s) to help provide a safe environment which includes cultural safety. This is a phrase originally coined by Maori nurses which means that there is no assault on a person's identity. The people most able or equipped to provide a culturally safe atmosphere are people from the same culture. We need to move on from the 'short term, cost effective, quick fix' approach to Indigenous issues, driven by economic imperatives, the clamouring of industry and conservative, hegemonic practices. To genuinely address the challenges of Indigenous health and education, the issue of cultural safety cannot be avoided. Critical reflection on experiential knowledge and defining or framing a debate on cultural safety is essential. This paper briefly examines some considerations for work practice.
Cultural Characteristics↗
Hepatitis C virus (HCV) specific immune responses in anti-HCV positive patients without hepatitis C viraemia.
BACKGROUND/AIMS: Most patients infected with hepatitis C virus (HCV) develop chronic infection and persistent viraemia. The immune mechanisms responsible for resolution of viraemia remain poorly understood. HCV specific humoral and cellular immune responses in patients with and without viraemia were investigated. METHODS: In vitro T helper (TH) lymphocyte responses to structural and non-structural HCV proteins were determined by means of proliferative response and cytokine production in 35 anti-HCV positive/HCV RNA negative patients and in 31 patients with chronic HCV infection and persistent viraemia. Humoral responses were determined by measuring HCV specific antibody quantity and specificity. RESULTS: A TH response to two or more HCV proteins was present in 18 of 35 patients with serological viral clearance compared with just one of 31 viraemic patients (p = 0.00001). HCV specific interferon-gamma production was increased only in the former group. In contrast, the antibody levels were significantly lower and directed at fewer HCV antigens in patients with undetectable HCV RNA. CONCLUSIONS: Patients without viraemia after HCV infection frequently have strong TH lymphocyte responses of the TH1 type to multiple HCV antigens many years after the onset of infection, whereas antibody responses are less marked. These results suggest that control of HCV replication may depend on effective TH lymphocyte activation.
Adult↗
HCV in hepatic failure: West and East do not meet.
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Genotype↗
A national audit of the laboratory diagnosis of tuberculosis and other mycobacterial diseases within the United Kingdom.
In order to audit United Kingdom laboratory diagnostic and reference services including novel molecular methods for tuberculosis, a questionnaire was sent to laboratories submitting specimens to the PHLS Mycobacterium Reference Unit (MRU) and regional centres and to the Scottish Mycobacteria Reference Laboratory (SMRL) in 1996-7. Nationally, 67.2% of laboratories responded. Most UK laboratories were fully or conditionally CPA accredited and take part in the NEQAS proficiency scheme. On average only 3.3% of primary samples submitted for mycobacterial diagnosis in 1995 produced a mycobacterial culture from approximately half as many patients (that is, a mean of 1488 specimens producing 49 isolates from 23 patients). Potentially over 380,000 specimens are processed for mycobacteria in the UK each year. The majority of laboratories use 4% NaOH +/- NALC for specimen decontamination. Culture on solid media was used by most laboratories and 62.9% also use liquid media. Most laboratories incubated cultures for eight weeks. Few laboratories use molecular diagnostic methods. Laboratories were most likely to use molecular methods for diagnosing tuberculous meningitis and for specimens from immunocompromised patients, although usage was strongly influenced by cost. Within England and Wales 43.9% (47/107) and 56% (61/109) of laboratories wanted a rapid service for rifampicin resistance detection in M tuberculosis from immunocompetent and immunocompromised patients, respectively. In regard to a tuberculous meningitis service, 80.5% (43/112) and 84.3% (102/121) of laboratories wanted this service for immunocompetent and immunocompromised patients, respectively. The quality of reference services was rated as "very good"/"good" by 85.6% of respondents nationally. Rapid molecular amplification diagnostic services were established at the PHLS MRU for rifampicin drug resistance detection nationally and for tuberculous meningitis at the MRU.
Bacteriological Techniques↗
Behaviours and expectations in relation to sexual intercourse among 18-20 year old Asians and non-Asians.
OBJECTIVES: To begin to map the reported behaviours and attitudes of young Britons of south Asian origin that may have implications for sexual health. "South Asian" refers to people able to trace their ancestry from the Indian subcontinent (that is, India, Pakistan, and Bangladesh), henceforth referred to as "Asian". DESIGN: A cross sectional study of sexual behaviour using self report measures in a self complete section of a social survey administered by trained interviewers in 1996. SETTING: Greater Glasgow, Scotland. SUBJECTS: Sample (n = 824) originally recruited aged 14-15 in 1992 in secondary schools in Greater Glasgow and subsequently traced through general practitioner registration for 1996 survey. 492 Asians and non-Asians aged 18-20 years old eventually interviewed in their own homes. MAIN OUTCOME MEASURES: Self reported experience of sexual intercourse, age at first intercourse, and contraceptive practice over year before interview. METHODS: Measures of sexual behaviour and attitudes were elicited through a self complete questionnaire filled out in the presence of, and returned to, a trained social interviewer. RESULTS: Asians, and particularly Asian women, were far less likely to report having had heterosexual intercourse. Those Asian women who had had intercourse were likely to do so for the first time at an older age, and with an older partner, than the non-Asian women. Asian women were less likely to report using the pill than non-Asian women, irrespective of their marital status, and Asian men were less likely than non-Asian men to report using condoms. Asian sexual abstinence was reported to be for religious reasons, which were not important for non-Asians. In contrast with non-Asians, Asians saw themselves as likely to be married with children within the next 5 years. Asian men considered the ideal age to marry for men and women to be younger than the non-Asian men's average estimate. Asian and non-Asian women suggested a similar ideal age for men to marry, but Asian women considered a younger age appropriate for women than did non-Asian women. CONCLUSIONS: The higher level of sexual abstinence among Asians, and particularly women, has implications for the delivery of sexual health services to the minority who are sexually active before marriage. The underreporting of condom use by Asian men compared with their non-Asian counterparts, suggests a failure of the existing sexual health education and health services to reach minority ethnic young men which may be remedied by collaborative work with institutions currently used by the Asian community.
Adolescent↗
Hospital days in risperidone-treated patients.
OBJECTIVE: To compare inpatient hospital days of a group of "real world" schizophrenia-spectrum patients for 3 years prior to and 3 years after risperidone initiation. METHOD: This is a retrospective cohort study using a mirror-image design of hospital days in 120 patients over a 6-year period. Hospital admission and discharge information was obtained from chart review and database extraction at 3 outpatient treatment sites. The sample comprised all patients attending these clinics who were prescribed risperidone during the first year of the drug's release. RESULTS: Patients separated into 3 treatment groups: those who were prescribed risperidone for 3 uninterrupted years (N = 35), those who interrupted but resumed risperidone use and were prescribed the drug at 3 years (N = 8), and those who discontinued risperidone during the 3-year follow-up period (N = 77). The group continuing risperidone to 3 years demonstrated a significant decrease in hospital days after risperidone treatment, in contrast to the other 2 groups. The reduction in inpatient days for the total sample was not statistically significant. CONCLUSION: In this outpatient clinic sample, the 29% of patients who continued on risperidone showed a significant reduction in inpatient hospital days, from an average of 17.2 days per year in the 3 years before risperidone treatment to an average of 2.1 days per year for the 3 years of risperidone treatment.
Adult↗