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Biomedical subjects

Roger W Chapman

Publications and source records attributed to Roger W Chapman.

10 recordsLinked to original sources
PubMed2006

The medical management of primary sclerosing cholangitis.

Primary sclerosing cholangitis raises several challenges for the physician. These include the identification of a drug regimen that slows or reverses the progression of the disease, the effective management of the symptoms of cholestasis, and the prevention of complications of the disease, including the development of colorectal cancer. The most studied drug in PSC is ursodeoxycholic acid, which, despite a range of potentially valuable actions on the cholestatic liver, has not yet been proven to make a substantial change in the course of the disease. However, it may yet prove to be sufficiently effective in the prevention of colorectal neoplasia to be prescribable for this reason alone. Better progress has been made in identifying agents that can alleviate pruritus and prevent the progression of osteopenia.

Cholagogues and Choleretics↗
PubMed2006

Sclerosing cholangitis.

PURPOSE OF REVIEW: Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by strictures of the biliary tree complicated by cirrhosis and cholangiocarcinoma. It is immune mediated although the precise etiology remains unknown. RECENT FINDINGS: Research into etiopathogenesis, epidemiology, the relationship with inflammatory bowel disease, diagnosis of cholangiocarcinoma, medical therapy, and the outcome of liver transplantation are discussed. SUMMARY: It is likely that a number of patients previously diagnosed with primary sclerosing cholangitis have autoimmune pancreatitis in association with primary sclerosing cholangitis, a syndrome with distinct clinicopathological features including steroid responsiveness. Primary sclerosing cholangitis-inflammatory bowel disease probably represents a distinct inflammatory bowel disease phenotype, which has implications for colonoscopic surveillance of these patients. CA19-9 plays no surveillance role for the early detection of cholangiocarcinoma. The best-studied drug in primary sclerosing cholangitis is ursodeoxycholic acid, which, despite a range of potentially valuable actions on the cholestatic liver, has not yet been proved to make a substantial impression on the course of the disease. Orthotopic liver transplantation remains the only established long-term treatment for primary sclerosing cholangitis.

Bile Duct Neoplasms↗
PubMed2005

Fatigue is not a specific symptom in patients with primary biliary cirrhosis.

BACKGROUND: Fatigue has been reported to be common in patients with primary biliary cirrhosis (PBC). Limited data exist on comparison with fatigue in the general population and comparison with patients with other chronic gastrointestinal disorders are lacking. METHOD: We enrolled 96 patients with PBC (87 females); mean age 63 (range 34-65) who completed the Fatigue Impact Scale (FIS). In comparison we included matched controls from the general population, patients with organic (OGD) and functional GI disorders (FGD). Liver function test and the latest liver biopsy were analysed and correlated with fatigue scores. RESULTS: The mean duration of PBC was 7.4 years, the mean bilirubin 13 micromol/l. Twelve per cent of patients had cirrhosis, 29% were in stage I on Ludwig's histology score and 30% and 29% were in stages II and III, respectively. The PBC patients had a median FIS total score of 29 in comparison with 38 in GP controls (P<0.05). Patients with OGD and FGD had more severe fatigue (FIS total score 67 and 59 (P<0.01 compared with PBC)). Fatigue in the PBC patients did not correlate with liver tests and histology stage. CONCLUSION: PBC patients had less severe fatigue measured with the FIS than controls from the GP and patients with OGD and FGD. This study also confirms results of other studies showing no correlation with fatigue in PBC and liver disease parameters. These results argues strongly against fatigue as a specific symptom in PBC.

Adult↗
PubMed2005

Sclerosing cholangitis.

PURPOSE OF REVIEW: Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by strictures of the biliary tree. It is immune mediated, although the precise cause remains unknown. Recent reports have shown a higher prevalence and burden of disease than was previously suspected. RECENT FINDINGS: The research into the etiopathogenesis, epidemiology, diagnosis of cholangiocarcinoma, medical and surgical therapy, and timing and outcome of liver transplantation is discussed. SUMMARY: Genetic heterogeneity among patients with primary sclerosing cholangitis is supported, and further gene polymorphisms associated with protection against primary sclerosing cholangitis have been elucidated. Bile duct injury seems to be a multistep process. Magnetic resonance cholangiopancreatography is a cost-effective and accurate way of diagnosing primary sclerosing cholangitis in comparison with endoscopic retrograde cholangiopancreatography. Ursodeoxycholic acid may have a role as a colorectal and hepatobiliary cancer chemopreventive agent. Liver transplantation remains the only treatment in end-stage disease. The 5-year and 10-year patient and graft survival rates are comparable with those in patients without primary sclerosing cholangitis, but there is a higher rate of retransplantation for primary sclerosing cholangitis in most centers. Hepatobiliary malignancy is found in a minority of patients at transplantation, although 5-year survival rates for these patients are still promising.

Cholangitis, Sclerosing↗
PubMed2004

Susceptibility to primary sclerosing cholangitis is associated with polymorphisms of intercellular adhesion molecule-1.

BACKGROUND/AIMS: Intercellular adhesion molecule-1 (ICAM-1, CD54) gene polymorphisms have been implicated in the susceptibility to a range of inflammatory diseases, including inflammatory bowel disease (IBD). Primary sclerosing cholangitis (PSC) is an immune-mediated chronic cholestatic liver disease associated with IBD. ICAM-1 is expressed on proliferating bile ducts and interlobular bile ducts in late stage PSC and serum levels of soluble intercellular adhesion molecules are increased in PSC. The aim of this study was to analyse ICAM-1 gene polymorphisms in PSC patients. METHODS: In this study, 104 patients with PSC and 213 healthy controls were recruited from Oxfordshire Caucasians. PCR with sequence-specific primers (PCR-SSP) was used to detect both ICAM-1 biallelic polymorphisms G241R and K469E. The results were controlled for the HLA haplotypes associated with PSC. RESULTS: The E/E frequency of K469E in PSC was 12% (12/104), significantly lower than that in controls (24%, 51/213;P = 0.009; Pc = 0.02; OR, 0.41). The occurrence of the haplotype G241-E469/G241-E469 in PSC was 4% (4/104), significantly lower than the control group (13%, 28/213; P = 0.01; Pc = 0.04; OR, 0.26). There was no difference between PSC and control groups in the frequencies of the genotype R241G or in allele frequencies of K469E. CONCLUSIONS: The E469E homozygote status for ICAM-1 is associated with protection against PSC.

Alleles↗
PubMed2004

Sclerosing cholangitis.

PURPOSE OF REVIEW: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by strictures of the biliary tree. It is closely associated with inflammatory bowel disease, particularly ulcerative colitis, although the precise etiology remains unknown. The prevalence of PSC, with its attendant medical burdens, appears to be higher than previously estimated; consequently, increasing numbers of patients are being diagnosed and treated in secondary care. RECENT FINDINGS: Research into etiopathogenesis, epidemiology, small-duct PSC, and associations with cholangiocarcinoma and colorectal carcinoma are discussed, along with medical therapy and transplantation. SUMMARY: Small-duct PSC is a distinct clinical entity associated with a benign course and minimal risk of cholangiocarcinoma compared with large-duct PSC. The incidence of gall bladder cancer is increased in patients with PSC, and yearly ultrasonographic screening, with cholecystectomy for gall bladder polyps, is recommended. Recent pilot studies have suggested that high-dose ursodeoxycholic acid (20 mg/kg body weight) may slow liver fibrosis and cholangiographic appearances. Importantly, ursodeoxycholic acid has also been shown to reduce the incidence of colonic dysplasia and colorectal cancer in patients with PSC and ulcerative colitis. Endoscopic therapy, usually balloon dilatation, is effective for benign dominant strictures that are causing jaundice. Liver transplant remains the only treatment in end-stage disease; however, posttransplant recurrence of PSC occurs in as many as one third of patients. Colorectal cancer develops posttransplant in 5 to 10% of those with inflammatory bowel disease. Annual screening colonoscopy is recommended for all patients with PSC with coexisting inflammatory bowel disease.

Journal Article↗
PubMed2003

Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis.

Haemochromatosis (HH) is a clinically and genetically heterogeneous disease caused by inappropriate iron absorption. Most HH patients are homozygous for the C282Y mutation in the HFE gene. However, penetrance of the C282Y mutation is incomplete, and other genetic factors may well affect the HH phenotype. Ferroportin and TFR2 mutations also cause HH, and two HAMP mutations have recently been reported that causes juvenile haemochromatosis (JH) in the homozygous state. Here, we report evidence for digenic inheritance of HH. We have detected two new HAMP mutations in two different families, in which there is concordance between severity of iron overload and heterozygosity for HAMP mutations when present with the HFE C282Y mutation. In family A, the proband has a JH phenotype and is heterozygous for C282Y and a novel HAMP mutation Met50del IVS2+1(-G). This is a four nucleotide ATGG deletion which causes a frameshift. The proband's unaffected mother is also heterozygous for Met50del IVS2+1(-G), but lacks the C282Y mutation and is heterozygous for the HFE H63D mutation. Met50del IVS2+1(-G) was absent from 642 control chromosomes. In family B, a second novel, less severe HAMP mutation, G71D, was identified. This was detected in the general population at an allele frequency of 0.3%. We propose that the phenotype of C282Y heterozygotes and homozygotes may be modified by heterozygosity for mutations which disrupt the function of hepcidin in iron homeostasis, with the severity of iron overload corresponding to the severity of the HAMP mutation.

Adult↗
PubMed2003

The management of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic hepatobiliary disease that usually progresses to biliary cirrhosis and liver failure; it also predisposes to cholangiocarcinoma. The cause of PSC is unknown, although evidence suggests that the tissue damage is mediated by the immune system. There is an unexplained close association between PSC and inflammatory bowel disease, particularly in ulcerative colitis, which coexists in the majority of patients with PSC. No medical therapy has been proven to halt or reverse disease progression; however, recent preliminary evidence suggests that ursodeoxycholic acid (UDCA) in a high dose of 20 to 25 mg/kg may slow the disease process. Evidence from a pilot study suggests that the combination of UDCA and immunosuppressive therapy, such as prednisolone or azathioprine, may also increase efficacy. For patients with end-stage PSC, liver transplantation remains the only effective therapy, although there is clear evidence that PSC may recur in the liver allograft.

Cholangitis, Sclerosing↗
PubMed2003

Sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disorder characterized by strictures and dilatations of the biliary tree. The median survival has been reported to be 12 years from diagnosis but patients diagnosed during the last decade have been shown to have longer survival of a median of 18 years. Small duct PSC seems to be an entity of its own and rarely progresses to large duct PSC and the prognosis of small duct PSC is much better than in large duct disease. Cholangiocarcinoma does not develop in patients with small duct PSC according to recently published studies. Autoantibodies binding to biliary epithelial cells have been demonstrated in sera from patients with PSC but the pathogenic role of these remains to be determined. It is suggested that inflammatory bowel disease is accelerated after orthotopic liver transplantation. MR cholangiopancreatography is increasingly used in clinical practice and has been reported to have similar diagnostic accuracy as ERCP. However, lack of standardization of this novel technology makes it unclear if it can supersede ERCP as a diagnostic tool in PSC at the present time. Better diagnostic tests to detect cholangiocarcinoma in patients with PSC are urgently needed.

Journal Article↗