Search PubMed⌕ Search

Biomedical subjects

O F James

Publications and source records attributed to O F James.

At least 37 records · Page 2Linked to original sources
PubMed1999

Portal hypertension secondary to arterio-portal fistulae: two unusual cases.

A 62-year-old male presented with variceal haemorrhage. Investigation demonstrated a fistula between the left gastric artery and portal vein with a porto-systemic gradient of 35 mm Hg. Variceal bleeding was controlled by a transcatheter embolisation of the fistula, but the patient died of septicaemia three weeks later. The second patient, a 42-year-old male who presented with variceal bleeding was shown to have diffuse arterio-venous fistulae involving the right lobe of the liver with a portosystemic gradient of 25 mm Hg. In this case the variceal bleeding was successfully controlled by insertion of a transjugular intrahepatic portosystemic shunt (TIPS). The pathogenesis of portal hypertension in arterioportal fistulae and the role of interventional radiological techniques in the management of variceal bleeding in these patients is discussed.

Adult↗
PubMed1999

Cancer risk in primary biliary cirrhosis: a study in northern England.

BACKGROUND: Suggestions that breast cancer may be more common in patients with primary biliary cirrhosis (PBC) have been challenged. It has recently been proposed that total cancer rates may be higher in patients with PBC, as well as liver cancers. AIMS: To investigate these proposals on a strictly defined case series. SUBJECTS: A total of 769 prevalent or incident PBC patients with "definite" or "probable" disease detected in a defined area of the north-east of England during 1987-94. METHODS: Cancer events and deaths were identified by obtaining information from one or more of the following sources: Office for National Statistics (ONS) Central Registers, Regional Cancer Registry, and clinical case records. Standardised cancer incidence (SIR) and mortality ratios (SMR) were calculated using the local region as the standard population. RESULTS: There were 97 cancer events during 1987-96. SIR from cancer registrations for all cancers was 1.7 (95% confidence interval (CI) 1.3 to 2.2), for liver cancer was 74 (95% CI 32 to 146), and for breast cancer was 1.1 (95% CI 0.4 to 2.4). SMR for all cancers was 1. 8 (95% CI 1.4 to 2.4), for liver cancer was 39 (95% CI 20 to 68), and for breast cancer was 0.4 (95% 0.1 to 1.6). The results were similar after excluding the first year of follow up after PBC diagnosis. CONCLUSIONS: There was some evidence of a small increase in overall cancer incidence and mortality in PBC patients. With the exception of liver cancer, it is unlikely that there is a high excess incidence for PBC patients from any cancer at a particular site, and specifically breast cancer.

Adolescent↗
PubMed1998

Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle.

It has been proposed that one mechanism for nerve and muscle dysfunction with age involves the mitochondria. Mitochondria contain the only DNA outside the nucleus in mammalian cells. Mitochondrial DNA (mtDNA) has a high mutation rate, and low levels of pathogenic mutations have been found in tissues from elderly subjects. However, the role of these mutations in the aging process is uncertain unless a mechanism can be identified that would lead to a biochemical defect. In muscle tissue from normal elderly subjects we show that there are muscle fibers with very low activity of cytochrome c oxidase, suggestive of a mtDNA defect. In these cytochrome c oxidase-deficient fibers we have found very high levels of mutant mtDNA. In addition, different mtDNA mutations are present in different fibers, which explains why there is a low overall incidence of an individual mutation in tissues from elderly subjects. These studies show a direct age-related correlation between a biochemical and genetic defect in normal human tissues and that mtDNA abnormalities are involved in the aging process in human muscle.

Aged↗
PubMed1998

Primary biliary cirrhosis: clinical and associated autoimmune features and natural history.

Primary biliary cirrhosis, a chronic liver disease, predominately affects middle-aged women. The diagnosis is established by the presence of disease-specific autoantibodies and compatible liver histology showing focal immune-mediated damage to the intrahepatic bile ducts. Patients now are detected prior to the onset of symptoms typical of cholestasis with abnormal liver function tests, or even prior to the onset of abnormal liver function tests, with positive antimitochondrial antibodies. Earlier diagnosis is changing not only our appreciation of the prevalence of this condition, but also of the natural history. The disease appears to be heterogeneous with some patients having a slow progression and a normal life-expectancy, although other patients have a more aggressive course developing symptoms and end-stage disease that leads to death or liver transplantation.

Autoimmunity↗
PubMed1998

Omeprazole, ranitidine, and cimetidine have no effect on peak blood ethanol concentrations, first pass metabolism or area under the time-ethanol curve under 'real-life' drinking conditions.

BACKGROUND: Considerable controversy persists over the influence of H2-receptor antagonists on the first pass clearance of ethanol. The majority of previously published studies have studied the effects of the drugs on low-dose ethanol in the fasting state. We elected to study the possible interaction under simulated real-life conditions. METHODS: Twenty-three volunteers were given 0.6 g/kg body weight ethanol in the form of 4.8% beer following a standardized meal. Blood ethanol levels were measured over the next 3 h. Studies were repeated using ethanol administered as an intravenous infusion while subjects consumed the same volume of de-alcoholized beer. The effects of a minimum of 2 weeks of dosing with cimetidine, ranitidine and omeprazole were examined. RESULTS: Following food, and with ethanol taken in the form of beer, mean first pass metabolism of ethanol was 58% (range 34-78%). No statistically significant difference was found following drug treatment in either percentage first pass metabolism, peak blood ethanol concentration or area under the time-blood ethanol curve. CONCLUSION: Under these 'real-life' conditions, the concomitant administration of cimetidine, ranitidine or omeprazole is unlikely to have significant physical, social or forensic implications, since they do not significantly change ethanol elimination.

Adult↗
PubMed1998

Is the SF-36 suitable for assessing health status of older stroke patients?

INTRODUCTION: The Medical Outcomes Study short form 36 health survey (SF-36) is being increasingly used and recommended as a suitable measure of subjective health status. However, it is unlikely that any measure will be appropriate for all groups. We wished to determine the suitability of the SF-36 for assessing quality of life in older stroke patients. METHODS: A screening questionnaire was used to identify prevalent cases of stroke from a random sample of 2000 subjects aged 45 years and over. The SF-36 was included as part of a self-completion questionnaire posted to each stroke patient. Data quality indicators were analysed. RESULTS: We identified 104 cases of stroke and the response rate for the SF-36 questionnaires sent was 83%. Completion rates for individual items ranged from 66 to 96%. All items in the role physical and role emotional scales had completion rates < 75%. The percentage of subjects for whom an individual scale score could be computed ranged from 67 to 96%, being lowest for the role physical and role emotional scales. Floor effects were high (> 15%) for these two scales and for the social functioning and physical functioning scales. Ceiling effects were substantial (> 15%) for the two role effect scales and for social functioning and bodily pain. CONCLUSIONS: This study has shown high response rates from older stroke patients to a postal questionnaire incorporating the SF-36. The poor completion rates and consequent inability to compute scores for a large proportion of responders in certain scales raises concerns about the perceived relevance of these sections. Results for the response effects suggest that, on its own, the instrument is not suitable for assessing outcome. When data quality indicators were examined, it appears that postal administration of the SF-36 is not appropriate for assessing quality of life of older stroke patients.

Activities of Daily Living↗
PubMed1998

The RsaI polymorphism of CYP2E1 and susceptibility to alcoholic liver disease in Caucasians: effect on age of presentation and dependence on alcohol dehydrogenase genotype.

Twin studies in Caucasians suggest that susceptibility to alcoholic liver disease is, in part, genetically determined. Because most of the deleterious effects of alcohol are caused by its metabolism, attention has focused upon genes encoding ethanol metabolizing enzymes. Caucasians are polymorphic at only two of these gene loci--cytochrome P450 2E1 (CYP2E1) and alcohol dehydrogenase 3 (ADH3). We examined the frequency of the RsaI polymorphism of CYP2E1 and ADH3 genotype in 264 patients with alcoholic liver disease and 121 local control individuals. There was a non-significant excess of the rare c2 CYP2E1 allele in patients with advanced liver disease compared with control individuals/patients with steatosis only (0.029 versus 0.017/0.00). However, patients with the c2 allele presented at a younger age compared with those with the wild type c1 allele only (42.3 +/- 1.6 years versus 49.0 +/- 0.6 years; P = 0.001) with at least as advanced histology (93% cirrhotic versus 74%). Male patients had a higher frequency of the ADH3*2/*2 genotype (which encodes the less active gamma2 subunit) than control individuals [odds ratio (OR) 2.04 (1.11-3.76)], however, ADH3 genotype did not differ with histological stage or with age of presentation. Patients with advanced disease possessing the c2 allele had a significantly higher frequency of the ADH3*2/*2 genotype compared with c1 homozygotes [OR 3.71 (1.24-11.09)]. This study demonstrates that, although rare in Caucasians, possession of the mutant c2 allele of CYP2E1 increases the risk of alcoholic liver disease at a given level of cumulative alcohol consumption. This risk appears to be particularly manifest in individuals carrying the ADH3*2 allele, presumably reflecting increased metabolism of ethanol by CYP2E1. In the absence of the c2 allele, ADH3 genotype does not influence the risk of advanced alcoholic liver disease but, in males at least, may influence the risk of alcoholism.

Age Distribution↗
PubMed1998

Heterozygotes for HFE mutations have no increased risk of advanced alcoholic liver disease.

BACKGROUND: Iron overload is common in the livers of alcoholics and may play a role in disease pathogenesis. An MHC like gene, HFE, has recently been identified that is mutated in most patients with hereditary haemochromatosis (C282Y in 90% and H63D in 45% of the remainder). AIM: To examine the hypothesis that these mutations determine hepatic iron status in alcoholics and play a role in pre-disposition to advanced alcoholic liver disease. METHODS: The HFE gene was genotyped in 257 patients with alcoholic liver disease and 117 locally matched healthy volunteers. In addition, iron staining was scored (0-4) on biopsy specimens from fibrotic/cirrhotic patients with and without HFE mutations matched for age and sex. RESULTS: Some 15.7% of fibrotic/cirrhotic patients were C282Y heterozygotes compared with 13.7% of controls (p = 0.77). One control and three patients were C282Y homozygotes. Of chromosomes without the C282Y mutation, 68/442 (15.4%) of patients' chromosomes carried the H63D mutation compared with 36/216 (16.6%) of control chromosomes (p = 0.91). Significant (> grade 1) hepatocyte iron staining was seen in 6/23 C282Y heterozygotes and 4/26 H63D heterozygotes compared with 4/23 controls. CONCLUSIONS: Possession of a single copy of either of the two HFE mutations influences neither liver iron content nor the risk of fibrotic disease in alcoholics.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised.

BACKGROUND: It has been proposed that a pathogenic effect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial. AIMS: To clarify the effects of H pylori infection on the mucus gel barrier in vivo. METHODS: Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pylori infection. RESULTS: There was a significant 18% reduction in the proportion of polymeric gel forming mucin in the adherent mucus layer in H pylori positive compared with negative subjects. There was no change in the adherent mucus thickness between H pylori positive and negative subjects without gastric atrophy (mean (SD): 104 (26) micron, 106 (30) micron, respectively). There was however a significant reduction in mucus thickness in those H pylori positive subjects with underlying gastric atrophy (84 (13) micron, p=0.03) compared with those without atrophy. CONCLUSIONS: A partial breakdown in gel forming structure of the gastric mucus barrier does occur in H pylori infection per se but this is insufficient to cause a collapse of the mucus barrier.

Aged↗
PubMed1997

Mitochondrial function in muscle from elderly athletes.

The extent to which mitochondria are involved in the aging process is controversial; much of the reported decline in mitochondrial oxidations in human skeletal muscle may be due to disease and inactivity rather than age. To study true aging, mitochondrial respiratory chain function was studied in 9 young and 12 elderly athletes. No significant deterioration with age was observed. If mitochondria are involved in aging, it must be through a more subtle mechanism than a global decline in respiratory chain activity.

Adult↗
PubMed1997

Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes.

In this study we have determined the incidence of hepatocellular carcinoma (HCC) development in primary biliary cirrhosis (PBC) and its effects on patient survival. Six hundred and sixty seven patients with liver histology compatible with or diagnostic of PBC were seen over a 20-year period. Two hundred and seventy three patients who had stage III or IV disease on their last biopsy and who had been followed up for at least 1 year following that biopsy (total follow-up with advanced disease 2,010 patient years) were identified (243 female, 30 male). Patients who developed HCC were identified and their confounding risk factors were excluded. Mayo risk scores were calculated for each clinic attendance and expected survival for each time point was compared with subsequent actual survival. Sixteen cases of HCC were seen in the patients with stage III or IV disease on last biopsy, providing an overall incidence of 5.9% in this group. Fourteen of these patients had died of HCC related causes, and 2 patients were alive at the census point. The incidence of HCC was significantly higher in males with stage III/IV disease than in females (20% vs. 4.1%, P < .005). Nine of one hundred and eight (8.3%) total female deaths in this group was attributable to HCC compared with 5 of 11 (45.5%, P < .05) male deaths. HCC was not seen in any of the 394 patients with stage I and II PBC followed-up over the same time period. Throughout the disease course of all PBC patients with HCC, the Mayo prognostic model over-predicted survival. Whereas it is a relatively rare complication of cirrhotic PBC in women, HCC is a relatively common cause of death in male PBC patients with cirrhosis. HCC typically develops several years after the onset of cirrhosis, and is poorly predicted by prognostic models. In view of these findings, consideration should be given to careful screening for HCC in male PBC patients with cirrhosis. The risk of HCC development may be an additional reason to consider earlier transplantation in these patients.

Aged↗
PubMed1997

Autoimmune hepatitis in older patients.

AIM: autoimmune hepatitis (AIH) is thought to present rarely in old people. The aims of the present study were to (i) review individuals diagnosed clinically as having AIH presenting over or under 65 years of age at Freeman Hospital, Newcastle, from 1979 to 1993 and (ii) compare diagnostic and histological scores, treatment and outcome, and hence provide a useful profile of the disease in older patients. METHODS: 310 individuals with a histological diagnosis of chronic hepatitis were identified, and review of the medical notes of 286 revealed 54 with a diagnosis of AIH. Of these, 12 (22%) were > or =65 years of age at presentation. RESULTS: at presentation, the mean diagnostic score (according to the diagnostic scoring system devised by an international panel; maximum score, 17) of the whole group was 11.5 (SD 3.5) and the mean score for those > or =65 years was 9 (SD 3). The mean histological grade (intensity of necro-inflammatory activity; maximum, 18) for the elderly group was 6 (SD 2) compared with 4.5 (SD 0.5) for the whole group. Despite this, 42% of the elderly sufferers had received no immunosuppressive therapy (versus 12% of the younger group). At follow-up, 26% in both groups had developed cirrhosis. None of the elderly group (but 7% of the younger group) had died from complications of chronic liver disease. CONCLUSION: we present data on 12 patients presenting at 65 years and over with AIH. In elderly individuals diagnosis may be more difficult, and treatment appears often to have been withheld. Despite this, and the more severe initial histological grade, the prognosis appeared no worse than in younger, usually correctly treated, patients.

Aged↗
PubMed1997

Incidence and prevalence of primary biliary cirrhosis in the city of Newcastle upon Tyne, England.

OBJECTIVE: To describe the incidence and prevalence of primary biliary cirrhosis in an urban population between 1987 and 1994, using stringent inclusion criteria and a well-defined study area and population. DESIGN: Descriptive study based on a case register compiled by a retrospective and prospective case-finding exercise and examination of case notes. SETTING: The city of Newcastle upon Tyne. MAIN INCLUSION CRITERIA: (1) Definite cases: fulfilling all three of the following diagnostic criteria: positive antimitochondrial antibody (AMA) > or = 1:40; cholestatic liver function tests (LFT); diagnostic or compatible liver histology. (2) Probable cases: fulfilling two of these criteria. SUBJECTS: All cases of primary biliary cirrhosis identified by multiple case-finding methods, alive from 1 January 1987 to 31 December 1994, in the defined area. MAIN OUTCOME MEASUREMENTS: Incidence and point prevalence rates by age and sex. RESULTS: In all, 202 potential cases were identified, of whom 160 met at least two inclusion criteria. In definite cases annual incidence varied from 14 to 32 (mean 22) per million whole population (with no clear trend) and point prevalence rose from 180 per million in 1987 to 240 in 1994. Mean age at diagnosis in cases incident during the study period was 63.2 years (S.D. 11.1 years, range 39.8-85.7 years). CONCLUSIONS: Primary biliary cirrhosis is much more common in Newcastle than has previously been reported anywhere in the world, and prevalence appears to be rising.

Adult↗
PubMed1997

Transjugular intrahepatic portosystemic shunt: a limited role in refractory ascites.

OBJECTIVE: To evaluate the role of the transjugular intrahepatic portosystemic shunt (TIPS) in the management of patients with refractory ascites. DESIGN: A retrospective study of 25 consecutive patients for whom refractory ascites was the primary indication for TIPS insertion. SETTING: Regional liver unit at Freeman Hospital, Newcastle upon Tyne, UK. PARTICIPANTS AND INTERVENTIONS: Twelve male and 13 female patients with a mean age of 58 years and mean Child-Pugh score of 10, treated with TIPS for refractory ascites between July 1992 and September 1995. MAIN OUTCOME MEASURES: Effect of TIPS on mortality, ascites and hospital admission rate. RESULTS: TIPS was successfully placed in all patients with a 59% mean reduction in portosystemic pressure gradient. Response rate was 68%, 48% and 33% at 1, 3 and 12 months, respectively. Mortality was 48% at 3 months and 67% at 12 months, being higher in those patients older than 60, those with renal impairment and those with higher Child-Pugh score. Amongst nine patients surviving long term (> 12 months) the mean time spent in hospital in the 3 months before TIPS was 35 days and in the year following TIPS 30 days. Patients who died (16 in total) spent a mean of 19 days in hospital before TIPS, 10 never leaving hospital, and 6 who were discharged spent a mean of 19 days post procedure in hospital (mean survival 84 days). CONCLUSION: TIPS has a limited role in the management of patients with refractory ascites. It is not an appropriate treatment where patients are older than 60, have renal impairment (creatinine > 200 mumol/l) or have a Child-Pugh score greater than 10.

Ascites↗