PubMed Health⌕ Search

Biomedical subjects

D Thorburn

Publications and source records attributed to D Thorburn.

At least 19 recordsLinked to original sources
PubMed2006

Treatment for mitochondrial disorders.

BACKGROUND: Mitochondrial respiratory chain disorders are the most prevalent group of inherited neurometabolic diseases. They present with central and peripheral neurological features usually in association with other organ involvement including the eye, the heart, the liver, and kidneys, diabetes mellitus and sensorineural deafness. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and premature death. Vitamin supplements, pharmacological agents and exercise therapy have been used in isolated cases and small clinical trials, but the efficacy of these interventions is unclear. OBJECTIVES: To determine whether there is objective evidence to support the use of current treatments for mitochondrial disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (searched September 2003), the Cochrane Central Register of Controlled Trials, MEDLINE (January 1966 to October 3 2003), EMBASE (January 1980 to October 3 2003) and the European Neuromuscular Centre (ENMC) clinical trials register, and contacted experts in the field. SELECTION CRITERIA: We included randomised controlled trials (including crossover studies) and quasi-randomised trials comparing pharmacological treatments, and non-pharmacological treatments (vitamins and food supplements), and physical training in individuals with mitochondrial disorders. The primary outcome measures included an improvement in muscle strength and/or endurance, or neurological clinical features. Secondary outcome measures included quality of life assessments, biochemical markers of disease and negative outcomes. DATA COLLECTION AND ANALYSIS: Details of the number of randomised patients, treatment, study design, study category, allocation concealment and patient characteristics were extracted. Analysis was based on intention to treat data. We planned to use meta-analysis, but this did not prove necessary. MAIN RESULTS: Six hundred and seventy-eight abstracts were reviewed, and six fulfilled the entry criteria. Two trials studied the effects of co-enzyme Q10 (ubiquinone), one reporting a subjective improvement and a significant increase in a global scale of muscle strength, but the other trial did not show any benefit. Two trials used creatine, with one reporting improved measures of muscle strength and post-exercise lactate, but the other reported no benefit. One trial of dichloroacetate showed an improvement in secondary outcome measures of mitochondrial metabolism, and one trial using dimethylglycine showed no significant effect. AUTHORS' CONCLUSIONS: There is currently no clear evidence supporting the use of any intervention in mitochondrial disorders. Further research is needed to establish the role of a wide range of therapeutic approaches.

Creatine↗
PubMed2005

Is interferon-alpha therapy safe and effective for patients with chronic hepatitis C and inflammatory bowel disease? A case-control study.

BACKGROUND: Hepatitis C virus infection is more common in patients with inflammatory bowel disease than in general population. Limited data are available as to the safety and efficacy of alpha-interferon therapy for chronic active hepatitis C in patients with concomitant inflammatory bowel disease. AIM: To evaluate the efficacy and safety of alpha-interferon monotherapy in patients with chronic active hepatitis C and inactive or mildly active inflammatory bowel disease. METHODS: A total of 513 consecutive inflammatory bowel disease patients at a single centre were tested for antibodies to hepatitis C virus (anti-hepatitis C virus) between 1995 and 2000. Twenty-one patients had detectable anti-hepatitis C virus Ab and were hepatitis C virus-RNA positive with histologically proved chronic active hepatitis. Each of these patients, whose inflammatory bowel disease was in clinical remission or mildly active, was sex- and age-matched to three controls with similar histological grade and stage of chronic hepatitis C virus but without inflammatory bowel disease; and all were treated with human leucocyte alpha-interferon 6 million units given thrice weekly for 12 months. Responses to treatment were classified as follows: complete response--persistently normal alanine aminotransferase and viral clearance (hepatitis C virus-RNA-ve) at the end-of-treatment, incomplete response--alanine aminotransferase normalization without viral clearance (hepatitis C virus-RNA+ve), and sustained response--alanine aminotransferase normalization and hepatitis C virus clearance 12 months after the end-of-treatment. RESULTS: Twenty-one patients with chronic active hepatitis C and inflammatory bowel disease (10 with Crohn's disease and 11 with ulcerative colitis) and 63 sex- and age-matched controls with chronic hepatitis C virus alone received alpha-interferon monotherapy. Response rates to interferon were similar for inflammatory bowel disease patients compared with controls [CR 42% vs. 35% and SR 24% vs. 18% (P, not significant), respectively]. None of the 21 inflammatory bowel disease patients had severe adverse effects and the mild ones observed were comparable with those seen in the control group. No patients developed an inflammatory bowel disease relapse during the interferon treatment period or in the 12 months thereafter. CONCLUSIONS: The biochemical and virological response to a 12-month human leucocyte alpha-interferon treatment in patients with chronic active hepatitis C are similar to that observed in matched controls with chronic hepatitis C virus without inflammatory bowel disease. Adverse effects are similar in both groups of patients and unrelated to the underlying inflammatory bowel condition. This provides hepatologists with evidence that alpha-interferon can be safely administered to patients with chronic hepatitis C virus and inflammatory bowel disease provided that the inflammatory bowel condition is in clinical remission.

Adult↗
PubMed2005

Polymorphisms of the renin-angiotensin system and the severity of fibrosis in chronic hepatitis C virus infection.

SUMMARY: Patients with chronic hepatitis C virus (HCV) infection vary in their rates of fibrosis progression. The renin-angiotensin system (RAS) regulates fibrosis. Polymorphisms in the genes of the RAS may contribute to the outcome of renal and cardiovascular disease. We studied four RAS gene polymorphisms in 195 patients with chronic HCV infection. Patients were grouped by Ishak stage of fibrosis on liver biopsy: group 1 (fibrosis score 0 or 1; n = 97), group 2 (fibrosis score 2 or 3; n = 73) and group 3 (fibrosis score 4-6; n = 25). Polymorphisms of the angiotensinogen (AGT) gene (M235T and AT-6), the angiotensin I converting enzyme gene and the type 1 angiotensin II receptor gene were assayed. There was no difference in the distribution of these polymorphisms of the RAS between the fibrosis groups. There did not appear to be any increased prevalence of fibrosis if two or even three of the polymorphisms associated with increased RAS effect were present. On multivariate analysis factors significantly associated with fibrosis were necroinflammatory activity (P < 0.001) and age (P < 0.001). No association was identified between these four RAS polymorphisms and fibrosis in chronic HCV infection.

Adult↗
PubMed2003

Epidemiological risk factors for hypersensitivity reactions to abacavir.

We investigated risk factors for hypersensitivity reactions (HSR) to abacavir in a case-control study. In a multivariate analysis, white race [odds ratio (OR), 5.16; 95% confidence interval (CI), 1.16-22.97] and a higher CD8 cell count at initiation of abacavir (>850 vs. < or =850 cells: OR, 3.74; 95% CI, 1.19-11.77) were found to be significantly associated with the development of HSR. Age, gender, stage of disease, prior antiretroviral exposure and type of concurrent antiretroviral therapy were not associated with HSR. Differences in predisposition to HSR according to ethnicity and baseline CD8 cell count may be explained by the reported MHC genetic associations with HSR.

Adult↗
PubMed2003

Risk of hepatitis C virus transmission from patients to surgeons: model based on an unlinked anonymous study of hepatitis C virus prevalence in hospital patients in Glasgow.

BACKGROUND: The risk of a surgeon acquiring the hepatitis C virus (HCV) through occupational exposure is dependent on the prevalence of HCV infection in the patient population, the probability of a percutaneous injury transmitting HCV, and the incidence of percutaneous injury during surgery. AIMS: To estimate the prevalence of HCV infection in the adult surgical patient population in North Glasgow and thereafter estimate the risk of HCV transmission to surgeons through occupational exposure. METHODS: The prevalence of HCV infection was estimated through the unlinked anonymous testing of samples from male surgical patients, aged 16-49 years, in two North Glasgow hospitals from 1996 to 1997, and adjusting these data for age and sex. Using published estimates of the incidence of percutaneous injury during surgery and percutaneous injury transmitting HCV, the risk of occupational transmission of HCV to surgeons was then derived. RESULTS: The estimated prevalence of anti-HCV infection for all adult patients in the two hospitals combined was 1.4% (cardiothoracic/cardiology 0.8%, orthopaedics/rheumatology 1.4%, general surgery/ENT 2.0%). The estimated probability of HCV transmission from an HCV infected patient to an uninfected surgeon was 0.001-0.032% per annum (0.035-1.12% risk over a 35 year professional career). CONCLUSIONS: The risk of an individual surgeon acquiring HCV through occupational exposure is low, even in an area with an extremely high prevalence of HCV among its injecting drug using population. Surgeons however should be encouraged to observe universal precautions and present for assessment after needlestick injuries to protect themselves and their patients from this insidious infection.

Adolescent↗
PubMed2003

Hepatic granulomas: a 10 year single centre experience.

BACKGROUND: Epithelioid granulomas have been reported in 2-15% of unselected liver biopsies, with numerous underlying aetiologies described. However, all UK series were reported before identification of hepatitis C virus (HCV). AIM: To evaluate the current aetiologies of hepatic granulomas and to assess the prognosis for the "idiopathic" group, in which all investigations for a recognised cause were negative or normal. METHODS: A retrospective review of patient case notes between 1991 and 2001; all patients who had a liver biopsy at Glasgow Royal Infirmary revealing epithelioid granulomas had their case notes and liver biopsies reviewed and a standard proforma completed. RESULTS: Over the study period, 1662 liver biopsies were performed. Hepatic granulomas were found in 63. Of those identified, 47 were female, with a mean age of 42 years (range, 17-81). Underlying aetiologies were as follows: primary biliary cirrhosis (PBC; 23.8%), sarcoidosis (11.1%), idiopathic (11.1%), drug induced (9.5%), HCV (9.5%), PBC/autoimmune hepatitis (AIH) overlap (6.3%), Hodgkin lymphoma (6.3%), AIH (4.8%), tuberculosis (4.8%), resolving biliary obstruction (3.2%), and other single miscellaneous causes (9.5%). Of the seven patients with idiopathic hepatic granulomas, one was lost to follow up, one died of stroke, and the remaining five were well with no liver related morbidity at a mean follow up of 6.2 years. CONCLUSIONS: The aetiology of hepatic granulomas is broad ranging, with HCV an important cause in this population. Despite extensive investigations, a 10-15% of patients still had "idiopathic" hepatic granulomas. However, the prognosis for this last group appears to be excellent.

Adolescent↗
PubMed2002

The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is frequently associated with elevated markers of iron stores. Recessively inherited mutations in the HFE gene are responsible for iron accumulation in most cases of hereditary haemochromatosis and may have a role in HCV infection. They may also be associated with progressive liver fibrosis although this remains controversial. AIMS: To assess the prevalence of HFE mutations in Scottish HCV infected patients and to explore the effect of the carrier state on serum and liver iron stores, and the severity of liver disease. PATIENTS: A total of 164 patients with antibodies to HCV who underwent liver biopsy were assessed prospectively. METHODS: Each patient was screened for HFE mutations (Cys282Tyr and His63Asp). Iron markers were assessed in serum (ferritin, transferrin saturation) and on liver biopsy (stainable iron, liver iron concentration (LIC) and hepatic iron index). RESULTS: There were 67 (41%, 26 Cys282Tyr, 33 His63Asp, eight compound) heterozygotes. Forty four (28%) patients had elevated serum iron markers, 24 (15%) had stainable liver iron, and five (3%) had elevated LICs. Carriage of HFE mutations was not associated with any clinical, biochemical, virological, or pathological features, including accumulation of liver iron. Elevated serum iron markers were associated with male sex, increased alcohol consumption, and increased liver inflammation and fibrosis. Patients with elevated LICs were older, acquired HCV infection earlier, and had more liver inflammation. CONCLUSIONS: Patients with chronic HCV infection frequently have elevated serum iron markers although elevated LICs are uncommon. Elevated serum iron studies and LICs occur in patients with more severe liver disease. Carriage of HFE mutations, although frequently observed in these HCV infected patients, does not have a role in the accumulation of iron or the progression of liver disease in HCV infection.

Adult↗
PubMed2001

Sequence variations in the NDUFA1 gene encoding a subunit of complex I of the respiratory chain.

NDUFA1 is one of the 36 nuclear genes encoding subunits of the mitochondrial complex I involved in the respiratory chain. The human NDUFA1 has been cloned, completely sequenced and mapped to Xq24. In the present study, we searched for sequence variations in NDUFA1 as causative defects in complex I deficiency using genomic DNA of 152 patients with various clinical phenotypes. The patient sample consisted of 54 patients (46 male and 8 female) with Leber heriditary optic neuropathy (LHON) from 48 unrelated families from Germany and 98 patients (72 male and 26 female) with biochemically proven complex I deficiency including Leigh syndrome. Patient DNA was used to amplify all three exons, including the exon/intron boundaries and the promoter region of NDUFA1 for heteroduplex analysis and direct sequencing. In the 152 patients tested, no mutation was found that could be related to any of the disease phenotypes included. However, three single-nucleotide polymorphisms (SNPs) located in the promoter region (SNP G/C at nt -71 and SNP T/C at nt -189) and in intron 1 (SNP T/G nt 1454) were discovered. Allele frequencies of the SNPs were estimated in a German and Estonian control population and compared to complex I-deficient patients. There was no significant difference between the control population, the LHON patients, or the severely affected patients with complex I deficiency, excluding an association of the polymorphisms with the diseases. Our results suggest that mutations in NDUFA1 do not cause the gender difference observed in clinically severe and complex phenotypes with complex I deficiency.

Alleles↗
PubMed2001

A study of hepatitis C prevalence in healthcare workers in the West of Scotland.

BACKGROUND AND AIMS: Whether healthcare workers have an increased prevalence of hepatitis C virus infection as a result of exposure to patient's blood and body fluids is controversial. This study assesses the prevalence of hepatitis C virus infection in healthcare workers, and its relation to the performance of exposure prone procedures and duration of occupational exposure, allowing an estimate to be made of the incidence of occupationally acquired hepatitis C infection among medical staff. METHODS: In this anonymous retrospective cohort study, we estimated the prevalence of hepatitis C infection in 10 654 healthcare workers. ELISA-3 testing was performed on pools of five sera collected during immunisation against hepatitis B. Healthcare workers were arranged into five occupational groups, according to the degree of patient exposure, and three age bands (<30 years, 30-39 years, >40 years). RESULTS: Prevalence of antibodies to hepatitis C was 0.28% (30/10 654), comparable in all occupational groups (p=0.34) and unrelated to duration of potential exposure. Assuming that all detected infections had been occupationally acquired, the maximum estimated risk of hepatitis C infection in exposure prone medical staff was low: 1.4% for surgeons and 1.0% for physicians over a 35 year professional career. CONCLUSIONS: Hepatitis C infection is infrequent in healthcare workers in Glasgow. Those conducting exposure prone procedures do not seem to be at higher risk than other healthcare staff.

Adult↗
PubMed1999

Prediction of single episodes of drinking during the treatment of alcohol-dependent patients.

Drinking episodes during the treatment (relapses or lapses) of alcohol-dependent patients is predicted from clinical ratings of patients and individual background data such as alcohol drinking history and social status. The probability of these relapses (or lapses) is determined up to three days in advance using a logistic regression procedure. The study group consisted of 33 male alcohol-dependent persons, who participated in a treatment program. Clinical ratings were performed three times a week by a trained person during a visit to the clinic. The questionnaire contained 23 different items about irritation, craving for alcohol. sleep disturbances, etc. The relapses were either self-reported or detected by a biochemical marker in a urine sample that was taken daily. The most important factor for a relapse in alcohol drinking was shown to be if the patient already had had one relapse during the treatment. Other important clinical factors were the levels of irritation and autonomic disturbances. None of the variables measuring mood shifts was significant. Family conditions during childhood were the most important background variables. The predictions turned out to have a rather high specificity, but the sensitivity was lower. Half of the relapses were not predicted by an increased probability for relapse. Self-reported relapses were predictable from preceding interviews and were also less frequent compared to those detected objectively by the biochemical markers.

Adult↗
PubMed1998

Viral kinetics can predict early response to alpha-interferon in chronic hepatitis C.

AIMS/BACKGROUND: Response rates to alpha-interferon therapy for chronic hepatitis C are poor. An early indication of efficacy would reduce the need for prolonged therapy, leading to significant cost savings. It was established that a change in quantitative hepatitis C virus RNA (HCV-RNA) titre at 4 weeks could predict the outcome of alpha-interferon therapy in chronic hepatitis C. METHODS: Serum HCV-RNA titres were quantified using branched chain DNA (bDNA) assay in 26 patients who responded to alpha-interferon (serum HCV-RNA negative after 12 weeks therapy) and 11 age and sex matched non-responders. Quantitative bDNA and qualitative RT-PCR assays for HCV-RNA were measured pretreatment and at 4 weeks. The change in quantitative HCV-RNA titre between pre-therapy and after 4 weeks was compared in the two groups. RESULTS: Seventeen of the 37 patients had become RT-PCR negative at 4 weeks (early responders) and had an undetectable HCV-RNA titre on bDNA assay. Nine patients were RT-PCR positive at 4 weeks but negative by 12 weeks (delayed responders), and of these, 8 had an undetectable viral titre at 4 weeks on bDNA assay. The patient with a detectable HCV titre did become RT-PCR negative after 12 weeks, but subsequently became RT-PCR positive again at 24 weeks. All the non-responders had a detectable bDNA titre (> 0.2 Meq/ml) at 4 weeks. CONCLUSIONS: Change in quantitative HCV-RNA titre measured by bDNA assay at 4 weeks predicts response to alpha interferon. If HCV-RNA remains detectable on bDNA assay at 4 weeks, no sustained response to treatment is found and alpha-interferon can be discontinued.

Hepacivirus↗
PubMed1997

Tumour seeding following percutaneous endoscopic gastrostomy placement in head and neck cancer.

We report the case of a patient with advanced squamous carcinoma of the supraglottic larynx and hypopharynx who developed metastatic gastric deposits occurring at the site of a percutaneous endoscopic gastrostomy tube, inserted 10 months previously by the pull technique. We review seven previous reports of tumour deposits occurring at the site of placement of a percutaneous endoscopic gastrostomy in patients with head and neck cancer, and consider alternative methods of enteral feeding in such patients.

Carcinoma, Squamous Cell↗
PubMed1996

alpha-Glutathione S-transferase levels in chronic hepatitis C infection and the effect of alpha-interferon therapy.

Serum alpha-glutathione S-transferase (alpha-GST) has been shown to be a sensitive marker of liver injury. We compared the relationship of both serum alpha-GST and alanine transaminase (ALT) with liver biopsy inflammatory activity in patients who had chronic hepatitis C infection (HCV), and examined the effects of alpha-interferon therapy on serum alpha-GST and ALT concentrations. Of 32 patients with chronic HCV infection studied, 17 received alpha-interferon 4.5 MU three times per week for 3 months and 15 acted as controls. Liver biopsy just prior to treatment was scored for the grade of inflammation (Scheuer histological activity index). Serum alpha-GST and ALT were assayed just prior to biopsy and 3 months later. Neither serum alpha-GST nor ALT levels showed any correlation with baseline inflammation on liver biopsy. alpha-Interferon significantly reduced serum alpha-GST concentration at 3 months (P = 0.01). ALT fell with treatment but not significantly (P = 0.05). Small falls in alpha-GST and ALT were noted in the control group, and when these were considered the significance of the changes in alpha-GST and ALT with treatment was lost (P = 0.35 and P = 0.09, respectively). This study shows that serum alpha-GST is not a useful marker of the degree of liver inflammation in chronic HCV infection, though it may be of more value than ALT in monitoring response to treatment with alpha-interferon.

Alanine Transaminase↗
PubMed1991

Treating AIDS patients.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗