PubMed Health⌕ Search

Biomedical subjects

C J Tibbs

Publications and source records attributed to C J Tibbs.

At least 19 recordsLinked to original sources

Stenosis of the pouch anal anastomosis following restorative proctocolectomy.

PURPOSE: To compare the incidence of stenosis after hand-sewn and stapled ileoanal anastomosis. Stenosis of the ileoanal anastomosis occurs in 5-16% of patients undergoing a restorative proctocolectomy but the incidence using a stapled technique is unknown. METHODS: Between 1976 and 1990, 266 patients underwent restorative proctocolectomy or proctectomy at one hospital. In two hundred and eighteen the anastomosis was hand sewn and stapled in 48 (single 33; double 15). RESULTS: Stenosis occurred in 31 (14.2%) of the hand-sewn and in 19 (39.6%) of the stapled anastomoses. This difference was highly significant (P < 0.001). Stenosis was not related to the size of the staple head used or to the stapling technique. There was no relationship between the development of stenosis and pelvic sepsis. Twenty six (hand-sewn 16, stapled 10) of the 48 patients with stenosis needed dilatation under general anaesthetic. CONCLUSION: Stapled anastomoses may result in a high incidence of anastomotic stenosis.

Adolescent↗

Usefulness and limitation of phylogenetic analysis for hepatitis C virus core region: application to isolates from Egyptian and Yemeni patients.

We report here the nucleotide sequences of the core region of HCV isolates from Egyptian and Yemeni patients and the method for classifying these HCV isolates by phylogenetic analysis. Sequence comparison suggested that the genotypes of these isolates were the same. Preliminary phylogenetic analysis of the HCV core region indicated that the genotypes of both isolates were 1c. However, an additional phylogenetic tree of the HCV core region constructed using a greater number of HCV isolates than that used in the preliminary analysis and on the basis of alignment of nucleotide sequences in an appropriate length indicated that the genotypes of these isolates were 4 and not 1c. For a more detailed analysis, the nucleotide sequences of the HCV E1 region as well as the core region for the same Yemeni patient were determined. A phylogenetic tree of the E1 region confirmed that the genotype of the HCV isolate from the Yemeni patient was 4. These data indicate that even when classifying HCV isolates using phylogenetic analysis, the misclassification would occur if care is not taken regarding the number and sequence lengths of the isolates included in the analysis.

Base Sequence↗

Liver transplantation for haemophiliacs with hepatitis C cirrhosis.

BACKGROUND: Experience of liver transplantation in haemophiliacs with end stage hepatitis C liver disease is limited and particularly difficult questions are raised when there is also HIV infection. AIMS: This is the first report in Great Britain to describe the operative replacement therapy and initial outcome in four haemophiliacs with end stage HCV cirrhosis. PATIENTS: Two patients had factor VIII, one had factor IX, and one had factor X deficiency. One patient had also contracted HIV infection from factor replacement but had no AIDS defining illnesses. METHODS: Intraoperatively patients were given either factor VIII infusions, factor IX bolus, or fresh frozen plasma, according to formulae devised to calculate exact clotting factor requirements. Baseline preoperative coagulation studies included prothrombin time, activated partial thromboplastin time, fibrinogen concentrations, and factor VIII, IX, and X concentrations. Factor concentrations were then assayed at 12, 24, 48, and 72 hours postoperatively. RESULTS: Postoperatively all patients had coagulation factor concentrations sustained within the normal ranges by 72 hours unsupported (137, 125, 95, 104 IU/dl), representing de novo synthesis by the graft. Transfusion requirements during the operative and immediate post-transplant period were no greater than those of patients without clotting disorders. Two patients had episodes of bleeding postoperatively, one of which was fatal, occurring at the site of a previous untreated subdural bleed. In both instances the bleeding occurred in the presence of normal concentrations of clotting factor. The remaining three patients are at 6, 6, and 12 months post-transplant and remarkably improved clinically with sustained factor concentrations. One patient has evidence of graft dysfunction from HCV recurrence and all have evidence of recurrent viraemia with HCV on polymerase chain reaction studies. CONCLUSIONS: Orthotopic liver transplantation should be considered in haemophiliac patients with end stage liver disease from hepatitis C infection with or without concomitant HIV infection. Their clinical condition is likely to be greatly improved by orthotopic liver transplantation and the haemophilia cured with only a small risk of severe graft dysfunction from recurrent HCV infection.

Adult↗

Hepatology.

Explore the source record for details and available documents.

Artificial Organs↗

Ribavirin therapy for hepatitis C infection following liver transplantation.

Hepatitis C infection following orthotopic liver transplantation may lead to progressive chronic graft dysfunction. In this study, seven liver transplant recipients with chronic allograft dysfunction due to hepatitis C infection (one acquired and six recurrent infections) were treated with oral ribavirin for 6 months. Symptoms of lethargy, nausea and anorexia improved in all patients within 2 weeks of starting the drug, with a fall in serum AST of at least 40% by this time. Ribavirin-induced haemolysis was clinically significant in three patients, necessitating a reduction in the daily dose of ribavirin from 1.2 g to 0.2 g. Comparison of the pre- and post-treatment biopsy specimens in the four patients who tolerated the full dose of ribavirin and who had normal AST levels at the end of 6 months of treatment showed significant histological improvement with reduction in either lobular or periportal inflammation in all of the patients and a reduction in periportal fibrosis in one patient. HCV RNA remained detectable in serum in all of the patients at the end of the study.

Female↗

Liver transplantation for acute and chronic viral hepatitis.

Hepatotrophic viruses are responsible for a substantial proportion of cases of both end-stage chronic liver disease and of acute liver failure which are treated by liver transplantation. We review here current practice in transplantation for viral-induced liver disease addressing, in particular, the selection of patients for transplantation and the increasingly recognized problem of recurrent disease in liver grafts.

Acute Disease↗

Methods of transmission of hepatitis C.

The route of transmission of hepatitis C virus is still controversial. Parenteral exposure via blood or blood products leads to infection in the majority of cases, and the majority of intravenous drug users become infected by repetitive exposure to contaminated injection equipment. The risk of infection from a single needlestick injury is 5-15% and may depend on the size of the innoculum. Other parenteral routes of transmission may include traditional healing practices and the use of contaminated medical equipment. Transmission is less common within a family but the prevalence of hepatitis C viral antibodies is higher in family members and sexual partners of carriers than in the general population. There are some well-documented instances of acute hepatitis C occurring after a defined sexual exposure. Vertical transmission is rare unless the mother has high levels of circulating HCV RNA as may occur in those also infected with HIV. The detection of hepatitis C in saliva and the higher than expected prevalence of infection in dentists may point to the possibility of transmission by salivary contamination. There remain large numbers of hepatitis C carriers in whom no route of infection can be identified.

Female↗

Serum intercellular adhesion molecule-1 levels in chronic hepatitis C: association with disease activity and response to interferon alpha.

Soluble intercellular adhesion molecule-1 (sICAM-1) is probably released from a variety of cells, including leukocytes and endothelial cells at sites of inflammation or in the circulation, and serum levels may therefore be used to give an indication of immune activation and inflammatory processes. In the present study, an ELISA was used to measure serum ICAM-1 levels in 43 patients with chronic hepatitis C and these were correlated with histological changes in the liver and the response to interferon alpha treatment. Serum ICAM-1 levels were significantly higher in patients with chronic hepatitis C infection than in normal subjects and correlated positively with the grade of histological activity, in particular the degree of portal, periportal, and lobular inflammation, but not with the presence of lymphoid aggregates. There was also a weak but significant positive correlation between sICAM-1 and serum aspartate aminotransferase activities, and sICAM-1 levels were substantially greater in patients with than those without cirrhosis. Serum ICAM-1 levels fell significantly in 11 responders out of 19 patients treated with interferon alpha, whereas levels remained unchanged in the non-responder group. sICAM-1 levels correlate with the clinical status of patients with chronic hepatitis C infection and fall with successful interferon treatment.

Adult↗

Does hepatitis C contribute to liver injury in alcohol abusers in the west of Scotland?

OBJECTIVE: To test the hypothesis that many patients with alcoholic liver disease have coexisting hepatitis C virus (HCV) infection which promotes the development of cirrhosis. DESIGN: Prospective, two-centre study comparing patients with alcoholic liver disease with HCV-positive blood donors identified by the Regional Blood Transfusion Service. SETTING: Two teaching hospitals in Glasgow, UK. PATIENTS: Sixty patients admitted to hospital with a diagnosis of alcoholic liver disease on the basis of clinical and histological tests. For comparison, a group of 50 anti-HCV-positive subjects identified from 305,012 blood donors during the same period (1991-1993) were questioned about their alcohol consumption and liver biopsy specimens are taken. MAIN OUTCOME MEASURES: The prevalence of HCV infection was determined by a second generation enzyme-linked immunosorbent assay (ELISA) for anti-HCV and by liver histology. RESULTS: No patients with alcoholic liver disease were anti-HCV-positive. Of the blood donors with chronic HCV infection, 11 (22%) reported previous or continuing consumption of more than 80 g alcohol daily for at least 2 consecutive years but liver histology in all 50 cases showed features characteristic of chronic HCV. There was no difference in liver histology between donors with a history of high alcohol consumption [mean grade 2.6 (range, 1-5), stage 0.4 (range, 0-2)] and abstinent, anti-HCV-positive donors [grade 2.8 (0-5), stage 0.5 (range 0-1)]. CONCLUSIONS: The absence of anti-HCV in this population of patients with alcoholic liver disease shows that HCV is not a necessary or a common cofactor in the development of alcoholic liver disease in the west of Scotland.

Adult↗

Hepatic and extrahepatic hepatitis C virus replication in relation to response to interferon therapy.

Response to a 1-yr course of interferon-alpha 2b was assessed in 18 patients with chronic hepatitis C virus infection in relation to clinical, biochemical and histological parameters and to the presence or absence of hepatitis C virus RNA and the presumed replicative form of the virus (negative-strand hepatitis C virus RNA) in serum, liver and peripheral blood mononuclear cells. The findings were compared with those in seven untreated patients studied over the same period. At the start of the study, positive-strand hepatitis C virus RNA was found in sera of all 25 patients, in livers of 24 and in peripheral-blood mononuclear cells of 19 of 22 tested; negative strand was found in livers of 11 and in peripheral-blood mononuclear cells of 15 of 22. Negative-strand hepatitis C virus RNA was not found in the serum of any patient at any stage. All of the five treated patients considered to show complete response during the study period cleared hepatic hepatitis C virus RNA, and four also became seronegative, but three had evidence suggestive of viral replication in their peripheral-blood mononuclear cells; two of these last patients subsequently relapsed. Loss of hepatic hepatitis C virus RNA was the only significant difference between these five and the seven partial and six nonresponders, but it is uncertain whether the observed changes were due specifically to interferon-induced modulation of virus expression because similar (apparently spontaneous) changes were seen in four of the untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Virus-induced autoimmunity in hepatitis C virus infections: a rare event.

Serial serum samples from 16 Italian patients presenting with acute hepatitis C virus (HCV) infections (which progressed to chronic hepatitis in six) were screened for the non-organ-specific autoantibodies most frequently associated with autoimmune hepatitis (AIH), as well as for antibodies against the hepatic asialoglycoprotein receptor (ASGP-R) and against the GOR peptide. One patient had low titres (1:10-1:80) of liver-kidney microsomal (LKM-1) antibodies during the recovery phase and three others had transient low titres of anti-smooth muscle (IgM class, 1:10) or anti-ASGP-R (1:150-1:300). Anti-GOR was detected in 43 (65%) of 66 sera from 13 of these patients. There was no correlation between any of these findings and progression to chronicity. By comparison, 18 patients with AIH studied concurrently before institution of immunosuppressive therapy all had antinuclear and/or smooth muscle antibodies, or LKM-1, at 1:40-1:640 and anti-ASGP-R at 1:300-1:2,100. None of these 18 had evidence of HCV infection and all were seronegative for anti-GOR. The findings indicate that the autoantibodies usually associated with AIH are rare in HCV infections but the virus can very occasionally induce a transient autoimmune response. Anti-GOR appears to be an antibody specifically related to HCV infection and is probably not a marker of induced autoimmunity, and it does not predict progression to chronic hepatitis.

Acute Disease↗

New genotype of hepatitis C virus in South Africa.

Partial nucleotide sequences in the core region of the hepatitis C viral genome were determined by reverse transcription followed by polymerase chain reaction, in a patient with chronic hepatitis from South Africa. These nucleotide sequences showed a low degree of homology with known types of HCV: the degree of homology between the nucleotide sequences of these clones with HC-J1, J4, J6, J7, Tr, and Eb-1 were 86.1-87.3%, 87.3-87.9%, 83.0-83.9%, 81.1-82.0%, 81.0-82.2%, and 82.8-83.4%, respectively, and that the deduced amino acid sequence homologies between these clones and HC-J1, J4, H6, J7, Tr, and Eb-1 were 90.7-91.6%, 89.7-91.6%, 91.6-93.5%, 90.7-91.6%, 81.5-82.4%, and 89.2-90.2%, respectively. The nucleotide sequence homologies of these clones with HC-J1, J4, J6, J7, Tr, and Eb-1 were very low, compared to those between the same genotype. Further comparison using molecular evolutionary methods suggested that this sequences should be classified in a new genotype.

Amino Acid Sequence↗

Nucleotide sequence of the core region of hepatitis C virus in Pakistan and Bangladesh and the geographic characterisation of hepatitis C virus in south Asia.

A large number of complete and partial hepatitis C virus (HCV) sequences have been reported and classified into several genotypes, although none have been reported from South Asia. We have determined and evaluated partial sequences in the core region of HCV obtained from patients with chronic hepatitis in Pakistan and Bangladesh. Nucleotide sequences from these viruses show significant homology with the Japanese HCV-TR isolate (91.7%-97.9%) and low homology with other Japanese, American, and UK isolates including HCV-1, HC-J4, HC-J6, HC-J8, and E-b1 (79.3%-86.2%). The homologies of their deduced amino acids sequence with HCV-1, HC-J4, HC-J6, HC-J8, E-b1, and HCV-TR were 84.3%-89.8%, 85.0-87.9%, 84.1%-86.9%, 84.3%-87.0%, 90.2%-93.1%, and 89.8%-93.5%, respectively. These results suggest that our clones might be classified into the same genotype as HCV-TR. Further analysis using molecular evolutionary methods strongly supported the classification of these sequences with the HCV-TR genotype. Moreover, we could not detect any isolates which were closely related to our clones or HCV-TR in countries outside the South Asian area. These data further support the association of HCV genotypes with distinct geographic regions.

Amino Acid Sequence↗

Cellular and humoral immune reactions against autoantigens and hepatitis C viral antigens in chronic hepatitis C.

BACKGROUND/AIMS: Previous reports have suggested that the hepatitis C virus (HCV) may induce autoimmune hepatitis. The aim of this study was to examine this hypothesis by investigating humoral and cellular immune responses to HCV-related antigens and various autoantigens in patients with chronic HCV infections. METHODS: Lymphoproliferative responses in vitro and/or circulating antibodies to an HCV core peptide, the putative autoantigen GOR, the liver-specific hepatic asialoglycoprotein receptor (ASGP-R), and other autoantigens were investigated in 27 adults with chronic hepatitis C. RESULTS: Five patients with HCV (18.5%) showed cellular immune responses to ASGP-R and two others had antibodies to ASGP-R, whereas 6 of 14 patients (42.8%) showed cellular responses to GOR and 7 of 14 patients (50%) showed responses to HCV core. Other autoantibodies were detected in three patients (11%). Nine patients with autoimmune hepatitis studied concurrently for comparison showed cellular and/or humoral responses to ASGP-R but not to GOR. Only 2 of 11 patients with other chronic liver disorders showed immune responses to any antigen tested. CONCLUSIONS: Specific immunocompetence against HCV-related antigens can often be shown in patients with chronic hepatitis C but is infrequently accompanied by autoreactions against liver-specific or nonspecific antigens. A reported association between T-cell responses to HCV core and lack of liver damage could not be confirmed.

Adult↗

Recurrence of hepatitis C following orthotopic liver transplantation: a polymerase chain reaction and histological study.

Hepatitis C virus was sought by nested polymerase chain reaction in the preoperative biopsy or the explanted liver of 100 consecutive adult patients undergoing orthotopic liver transplantation. In those found to be positive preoperatively, polymerase chain reaction was performed on subsequent biopsies. Of the 12 patients in whom HCV-RNA was identified in the liver by polymerase chain reaction preoperatively, viral recurrence was documented in ten of the 11 with posttransplant liver tissues available for study. In the one exception, hepatitis C virus was undetectable in the liver graft despite repeated co-amplification of albumin mRNA as an internal control, which may indicate viral clearance. In eight of the ten positive cases, HCV-RNA was also detectable in serum postoperatively, while HCV-RNA was undetectable in serum in both the cases in whom HCV-RNA was undetectable in tissue and in the patient who declined post-transplant biopsy. Two of the 12 patients infected with hepatitis C virus preoperatively have died during the follow-up period from causes unrelated to hepatitis C virus infection. While biochemical liver function in seven of those remaining has been excellent, histological evidence of at least mild chronic active hepatitis has been present in all ten cases for whom long-term biopsies are available. Three cases have progressed to severe, symptomatic chronic active hepatitis within 2 years of transplantation. Recurrent hepatitis C is associated with progressive liver disease and appreciable morbidity in a significant proportion of patients.

Adult↗

Temporary loop ileostomy for restorative proctocolectomy.

The aim of a defunctioning ileostomy after restorative proctocolectomy is to mitigate the consequences of pelvic sepsis, should it occur. However, there are complications related to the ileostomy itself. Of 310 patients (174 male and 136 female; mean age 33.2 years) who underwent restorative proctocolectomy between 1976 and 1990, 296 had a covering ileostomy and 14 did not. The stoma has been closed in 263 (88.9 per cent) at a median interval from formation of 12.0 weeks. Ileostomy-related complications before closure occurred in 17 patients (5.7 per cent). Laparotomy for obstruction due to the ileostomy was required in seven patients (2.4 per cent). Retraction requiring revision occurred in three patients (1.0 per cent), an abscess behind the stoma in one (0.3 per cent) and miscellaneous appliance problems in seven (2.4 per cent). Following closure, 59 patients overall (22.4 per cent) developed an ileostomy-related complication. There were 30 cases of small bowel obstruction, treated conservatively in 19 (7.2 per cent) and by laparotomy in 11 (4.2 per cent). Peritonitis requiring laparotomy occurred in three patients (1.1 per cent) and two (0.8 per cent) developed an enterocutaneous fistula. There were 14 (5.3 per cent) wound infections and 16 (6.1 per cent) other miscellaneous problems. Significant complications associated with a temporary ileostomy were less frequent in this series than in some other reports. Obstruction was the most common complication and fistula was rare.

Adolescent↗