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Biomedical subjects

S D Ryder

Publications and source records attributed to S D Ryder.

At least 19 recordsLinked to original sources
PubMed2007

Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex.

Mannan-binding lectin (MBL) binds microorganisms via interactions with glycans on the target surface. Bound MBL subsequently activates MBL-associated serine protease proenzymes (MASPs). A role for MBL in hepatitis C virus (HCV) infection had been indicated by previous studies examining MBL levels and polymorphisms in relation to disease progression and response to treatment. We undertook this study to investigate a possible relationship between disease progression and functional MBL/MASP-1 complex activity. A functional assay for MBL/MASP-1 complex activity was employed to examine serum samples from patients with chronic HCV infection, non-HCV liver disease and healthy controls. Intrapatient consistency of MBL/MASP-1 complex activity levels was assessed in sequential samples from a subgroup of patients. Median values of MBL/MASP-1 complex activity were higher in sera from patients with liver disease compared with healthy controls. MBL/MASP-1 complex activity levels correlate with severity of fibrosis after adjusting for confounding factors (P = 0.003). MBL/MASP-1 complex activity was associated more significantly with fibrosis than was MBL concentration. The potential role of MBL/MASP-1 complex activity in disease progression is worthy of further study to investigate possible mechanistic links.

Adolescent↗
PubMed2006

Clinical pathways for patients with newly diagnosed hepatitis C - what actually happens.

Management of hepatitis C virus (HCV)-infected individuals requires referral to specialist care. To determine whether patients newly diagnosed as anti-HCV positive are appropriately referred for further investigation and management, and if not, to determine why not. We studied patients tested for antibodies to HCV by Nottingham Public Health Laboratory in a 2-year period (2000-2002). The progress of newly diagnosed anti-HCV positive patients into specialist clinics for further management was documented. For patients not referred for specialist care, a questionnaire was sent to the clinician requesting the initial anti-HCV test, to identify reasons for nonreferral. Eleven thousand one hundred and seventy-seven patients were tested for anti-HCV. Two hundred and fifty-six (2.3%) were newly diagnosed as being anti-HCV positive. Two per cent of samples sent from primary care were anti-HCV positive, compared to 18.8, 18.9 and 1.3% sent from prison, drug and alcohol units, and secondary care, respectively. About 64.3% of positive patients diagnosed in primary care were referred to specialist care, compared to 18.4, 42.4 and 62.6% of patients diagnosed in the other three settings. One hundred and twenty-five (49%) newly diagnosed patients were referred appropriately for further management. 68 of these attended clinic, 45 underwent liver biopsy and 26 (10%) began treatment. One hundred and thirty-one patients (51%) were not referred. In 54 cases, there was no evidence that the anti-HCV positive result reached the patient. In 15, referral was considered but rejected, and 20 patients were referred to non-HCV-specialists (their general practitioners or to genito-urinary medicine). Hence less than 50% of newly diagnosed anti-HCV positive patients are referred to an appropriate clinic for further investigation and management. Reasons for this are multifarious and complex, reflecting both systems failure and patient choice. Unless these are understood and addressed, the Department of Health Hepatitis C Strategy (2002) and Action Plan for England (2004) will fail to achieve their intended objectives.

Adolescent↗
PubMed2004

Fracture risk of women with primary biliary cirrhosis: no increase compared with general population controls.

AIM: Patients with primary biliary cirrhosis may be at increased risk of osteoporosis but to what extent this is reflected in an increased fracture risk is unknown. We have enquired about the fracture experience of female primary biliary cirrhosis patients compared with sex- and age-matched controls. METHODS: Patients aged 30-75 with primary biliary cirrhosis and age-matched controls were sent a postal questionnaire asking about their fracture history and details of risk factors for osteoporosis. RESULTS: 85 eligible patients with primary biliary cirrhosis and 116 controls responded. Forty-one per cent of patients with primary biliary cirrhosis and 30% of controls reported ever having had a fracture odds ratio 1.5 (95% confidence interval: 0.80-2.89). Twenty-eight per cent of primary biliary cirrhosis patients and 23.3% of controls reported a fracture after the age of 30, odds ratio 1.2 (95% confidence interval: 0.57-2.56), and 14.1% of primary biliary cirrhosis patients and 12.1% of controls reported a low impact fracture of the long bones or of the vertebrae odds ratio 1.0 (95% confidence interval: 0.31-2.68). CONCLUSIONS: No overall increased fracture risk in patients with primary biliary cirrhosis was observed. As a group, unselected patients with primary biliary cirrhosis do not represent a population at particularly high risk of osteoporotic fracture and thus targeting them for osteoporosis screening and treatment is not justified. Further work investigating subgroups of patients with primary biliary cirrhosis at potentially high risk of osteoporosis, such as those with advanced disease or severe cholestasis is required.

Adult↗
PubMed2004

A pilot study to investigate the use of oxpentifylline (pentoxifylline) and thalidomide in portal hypertension secondary to alcoholic cirrhosis.

BACKGROUND: Tumour necrosis factor-alpha is thought to be important in the pathogenesis of portal hypertension. Oxpentifylline (pentoxifylline) and thalidomide inhibit endotoxin-induced tumour necrosis factor-alpha production in vitro. AIMS: To assess the toxicity of oxpentifylline (pentoxifylline) and thalidomide in cirrhosis and their effect on the hepatic venous pressure gradient and tumour necrosis factor-alpha production. METHODS: In an open-label pilot study, 20 abstinent patients with stable alcoholic cirrhosis and oesophageal varices were recruited; 12 patients completed haemodynamic measurements before and after treatment with oxpentifylline (pentoxifylline) 1800 mg (n=6) or thalidomide 200 mg (n=6) daily for 2 weeks. Tumour necrosis factor-alpha production was assessed in ex vivo monocyte cultures stimulated with endotoxin. RESULTS: Thalidomide reduced the hepatic venous pressure gradient from 19.7 mmHg (9.3-23.5 mmHg) to 12.2 mmHg (4.7-19.5 mmHg) (P=0.03) without reducing the hepatic blood flow or altering systemic haemodynamic parameters. Thalidomide reduced ex vivo tumour necrosis factor-alpha production by approximately 50%. Oxpentifylline (pentoxifylline) had no significant effect on any of the parameters measured. Side-effects led to dose reduction or treatment withdrawal in 40% of patients. CONCLUSION: Thalidomide, but not oxpentifylline (pentoxifylline), reduces the hepatic venous pressure gradient in stable alcoholic cirrhotics, an effect that may be mediated by the inhibition of tumour necrosis factor-alpha production. The role of tumour necrosis factor-alpha inhibitory drugs in the therapy of portal hypertension should be investigated in a randomized controlled trial.

Adult↗
PubMed2004

Improving diagnostic yield of biliary brushings cytology for pancreatic cancer and cholangiocarcinoma.

Biliary brushings are currently the best accepted method to obtain a cytological diagnosis of pancreatic cancer or cholangiocarcinoma. The technique has good specificity but poor sensitivity. Two dedicated pathologists reviewed 137 consecutive biliary brushings from 127 patients between February 1997 and February 2000. The ultimate diagnosis was determined by review of radiology, operative diagnosis and patient outcome. The sensitivity, specificity, positive predictive value and negative predictive value of the original results and the review results were calculated and compared. Additional diagnostic categories 'suspicious' and 'atypical possibly benign' were included on review. After review, the sensitivity improved from 49.4% to 89.0% and the specificity remained 100%. The use of the additional diagnostic category 'suspicious' increased the sensitivity to 90.4%, at the expense of a fall of the specificity to 66.7%. We conclude that review by two dedicated pathologists and additional diagnostic categories can improve the diagnostic accuracy of biliary brushings.

Adolescent↗
PubMed2004

Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study.

BACKGROUND: The natural history of hepatitis C virus (HCV) infection remains uncertain. Previous data concerning rates of progression are from studies using estimated dates of infection and single liver biopsy scores. We prospectively studied the rate of progression of fibrosis in HCV infected patients by repeat liver biopsies without intervening treatment. PATIENTS: We studied 214 HCV infected patients (126 male; median age 36 years (range 5-8)) with predominantly mild liver disease who were prospectively followed without treatment and assessed for risk factors for progression of liver disease. Interbiopsy interval was a median of 2.5 years. Paired biopsies from the same patient were scored by the same pathologist. RESULTS: Seventy of 219 (33%) patients showed progression of at least 1 fibrosis point in the Ishak score; 23 progressed at least 2 points. Independent predictors of progression were age at first biopsy and any fibrosis on first biopsy. Factors not associated with progression were: necroinflammation, duration of infection, alcohol consumption, alanine aminotransferase levels, current or past hepatitis B virus infection, ferritin, HCV genotype, and steatosis or iron deposition in the initial biopsy. CONCLUSIONS: One third of patients with predominantly mild hepatitis C showed significant fibrosis progression over a median period of 30 months. Histologically, mild hepatitis C is a progressive disease. The overall rate of fibrosis progression in patients with hepatitis C was low but increased in patients who were older or had fibrosis on their index biopsy. These data suggest that HCV infection will place an increasing burden on health care services in the next 20 years.

Adolescent↗
PubMed2001

Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology.

BACKGROUND/AIMS: The significance of abnormal liver function tests in the absence of diagnostic serology is unclear. The aim of this study was to report liver biopsy findings in a large group of patients with unexplained abnormal liver biochemistry. METHODS: Histological findings were examined in 354 patients who underwent liver biopsy to investigate abnormal liver function tests. RESULTS: Six percent of patients had a normal liver biopsy while 26% were found to have some degree of fibrosis and 6% were cirrhotic. Thirty four and 32% of biopsies suggested non-alcoholic steatohepatits or fatty liver respectively. Other diagnoses included cryptogenic hepatitis, drug toxicity, primary and secondary biliary cirrhosis, autoimmune hepatits, alcohol-related liver disease, primary sclerosing cholangitis, haemochromatosis, amyloid and glycogen storage disease. Patient management was directly altered in 18% of patients due to liver biopsy findings and three families were entered into screening programmes for inheritable liver disease. CONCLUSIONS: The finding of abnormal liver function tests in the absence of diagnostic serology may indicate significant liver disease. Liver biopsy yields a range of liver diseases of diverse nature and extent. Liver diseases may be uncovered for which specific treatment is indicated.

Biopsy, Needle↗
PubMed2000

Mycophenolate mofetil for maintenance of remission in autoimmune hepatitis in patients resistant to or intolerant of azathioprine.

BACKGROUND/AIM: Azathioprine is standard therapy for maintenance of remission in patients with autoimmune hepatitis. However, approximately 15% of patients are intolerant of therapy and 10% do not respond to it. There is a need for alternative therapies. We describe here the results of mycophenolate mofetil therapy in patients with autoimmune hepatitis. PATIENTS: We studied seven patients with type 1 AIH (six female). Three were intolerant of azathioprine and had elevated transaminases and liver histology showing active disease despite prednisolone therapy. Four had been on a dose of 2 mg per kg of azathioprine without complete normalisation of ALT, and had liver biopsies showing active disease. All were treated with mycophenolate 1 g bd and were followed for a median of 46 months (21-59). End points were improvement in histological inflammation, ALT and prednisolone dose. RESULTS: Five of the seven (71%) patients had normal transaminases after 3 months of treatment. The steroid dose fell from a median of 20 mg per day to 2 mg per day at 9 months (p=0.0001) and the hepatic activity index fell from median 11 to 3 (p=0.001) after 7 months of therapy. One patient required dose reduction because of a fall in white cell count. No other adverse effects were seen. CONCLUSIONS: Mycophenolate mofetil is effective and well tolerated in patients with type 1 AIH who are intolerant of, or do not respond to, azathioprine.

Adolescent↗
PubMed1999

p53 mutations in british patients with hepatocellular carcinoma: clustering in genetic hemochromatosis.

BACKGROUND & AIMS: Environmental factors are important in the etiology of hepatocellular carcinoma (HCC). Aflatoxin B1 causes a specific point mutation in the p53 tumor-suppressor gene in exposed individuals. In Western populations, mutations of this gene seem to be less frequent. We have investigated the role of p53 mutations in tumorigenesis in British patients with HCC. The aim of this study was to determine the frequency and mutational spectrum of the p53 gene in HCCs from British patients. METHODS: DNA from 170 HCCs, of well-defined etiology, in British patients was analyzed by single-stranded conformational polymorphism using the polymerase chain reaction technique. Mutations were then characterized by direct sequencing. RESULTS: Twenty-nine percent of tumors had p53 mutations. Ten of 14 (71%) hemochromatotic cancers had mutations within the p53 gene, and clustering of these mutations at codon 220 (A-G) was found in 5 cases; 3 others had T-A mutations. No clustering was found in HCCs with other etiologies. CONCLUSIONS: p53 mutations are more common than was thought in Northern European HCCs. This is the first demonstration of p53 mutational clustering in HCCs from hemochromatotic subjects.

Aged↗
PubMed1999

Saphenoperitoneal shunts for patients with intractable ascites associated with chronic liver disease.

BACKGROUND: Ascites is a common complication in patients with chronic liver disease. Some patients are resistant to diuretics and need therapeutic paracentesis on a regular basis. This is inconvenient in the long term and also has resource implications. Alternatively, these patients may be treated by peritoneovenous shunts, which require insertion of a foreign body into a central vein and are prone to occlusion. A new technique for peritoneovenous shunting without the use of foreign material is described. METHODS: Eight patients with chronic liver disease and diuretic-resistant ascites underwent this procedure. During operation, the long saphenous vein was divided at the mid-thigh level and inverted towards the inguinal canal, where it was anastomosed directly to the peritoneum at the internal inguinal ring using non-absorbable suture material. RESULTS: Seven patients had successful shunt formation; the remaining patient had to have the shunt removed because of ascitic leakage. In those who underwent successful shunt formation, the need for paracentesis and the dose of diuretic was significantly reduced over a median follow-up of 8 months. Hospital stay in the month after discharge was significantly less than that in the month before operation. Three patients died during follow-up from causes unrelated to the operation. One patient underwent successful liver transplantation. CONCLUSION: This study suggests that saphenoperitoneal shunting is potentially a safe and effective therapy for patients with diuretic-resistant ascites. It retains the benefits of peritoneovenous shunting without the adverse effects of insertion of foreign material.

Ascites↗
PubMed1999

TT virus infection in patients with hepatitis C: frequency, persistence, and sequence heterogeneity.

TT virus (TTV) was recently identified in the serum of a patient with hepatitis. The role of TTV in liver disease has not been established. Three polymerase chain reaction (PCR) protocols were used to detect TTV DNA in sera of persons infected with hepatitis C virus (HCV) and in blood donors. Sera from 11.5% of HCV-infected patients and 7.7% of blood donors were positive by protocols 1 or 2. In contrast, 48.7% and 57.7% of sera, respectively, were positive when tested by protocol 3. There was no difference in the severity of hepatitis in persons coinfected with TTV and HCV when compared with those infected with HCV alone, regardless of which TTV PCR protocol was used. TTV DNA persisted in serum samples taken up to 6 years apart in individual patients. Sequence analysis indicated that most viral sequences were distinct between patients, and there was evidence of genetic heterogeneity and viral evolution within individuals.

Adolescent↗