PubMed Health⌕ Search

Biomedical subjects

E J Gane

Publications and source records attributed to E J Gane.

15 recordsLinked to original sources
PubMed2006

Low-cost, simultaneous, single-sequence genotyping of the HLA-A, HLA-B and HLA-C loci.

New automated DNA sequencing technology has enabled the development of an assay for genotyping the three major HLA class 1 loci from a single sequence of each gene containing exon 3, intron 2 and exon 2. The assay allows 31 subjects (with 3 negative controls) to be genotyped at all three loci simultaneously, using a 96-well plate format. Genotypes were assigned by comparing each sequence to a database of 307 HLA-A, 563 HLA-B and 166 HLA-C alleles. Unequivocal, 4-digit allele assignments were made for 40 of 130 HLA-A genes, 82 of 130 HLA-B genes and 97 of 130 HLA-C genes from 21 European, 20 Tongan and 24 Niuean subjects. Ambiguity in interpretation of the sequence contributed to 66 of the 170 equivocal allele assignments, and 105 equivocal assignments were due to polymorphisms outside exons 2 and 3. All known alternative interpretations of ambiguous genotypes were identified, and seven HLA-B and two HLA-C ambiguities were resolved by reading the out-of-phase exon 2 sequence that followed an indel in intron 2. The genotypes of a subgroup of 27 heterozygous subjects, whose genotypes contained all of the alleles identified in this study, were confirmed with commercial, generic PCR-SSP typing. In European subjects, the repertoire of HLA-B/HLA-C haplotypes was almost identical to previously published data. We identified five new HLA-B/HLA-C haplotypes in the Polynesian subjects, and the remaining haplotypes were of Asian origin. In summary, we are describing a low-cost, sequencing assay for the three major HLA class I loci that provides a level of resolution that is comparable with a commercial PCR-SSP assay.

Alleles↗
PubMed2003

Liver transplantation for HCV-associated liver cirrhosis: predictors of outcomes in a population with significant genotype 3 and 4 distribution.

End-stage liver disease associated with hepatitis C virus (HCV) infection is now the leading indication for liver transplantation in adults. However, reinfection of the graft is universal. We aimed to determine predictors of outcome of HCV-liver transplant recipients in the Australian and New Zealand communities. The following variables were analysed: demographic factors, coexistent pathology at the time of transplantation, HCV genotype, and donor age. Outcomes measures were: 1. mortality; 2. development of HCV-related complications, which were stage 3 or 4 fibrosis, or mortality from HCV-related graft failure, or both. Between January 1989 and December 30, 1999, 182 patients were transplanted for HCV-associated cirrhosis. The median follow-up period was 4 years (range, 0 to 13 years). Genotype data were available on 157 patients. The distribution of genotypes among the 157 patients was as follows: 36 (23%) genotype 1a, 30 (19%) genotype 1b, 4 (9%) genotype 1, 17 (11%) genotype 2, 41 (26%) genotype 3a, and 16 (10%) genotype 4. Eight (5%) patients were HCV-polymerase chain reaction (PCR)-negative (but HCV-antibody-positive). Donor age and genotype 4 were associated with an increased risk of retransplantation or death (P <.001 and.05, respectively). Meanwhile, donor age, genotype 4, and pretransplant excess alcohol were risk factors for the development of HCV-related complications (P =.004,.008, and.02, respectively). In contrast, patients with genotype 3a were less likely to develop HCV-related complications (P =.05). In a population of HCV liver transplant recipients with a heterogeneous genotype distribution, donor age, and genotype 4, were predictors of a worse outcome, whereas genotype 3 was associated with a more favorable outcome.

Adult↗
PubMed2001

Sequential changes in the metabolic response to orthotopic liver transplantation during the first year after surgery.

OBJECTIVE: To quantify the sequential changes in the metabolic response occurring in patients with end-stage liver disease after orthotopic liver transplantation (OLT). SUMMARY BACKGROUND DATA: Detailed quantification of the changes in energy expenditure, body composition, and physiologic function that occur in patients after OLT has not been performed. Understanding these changes is essential for the optimal management of these patients. METHODS: Fourteen patients who underwent OLT for end-stage liver disease had measurements of resting energy expenditure, body composition, and physiologic function immediately before surgery and 5, 10, 15, 30, 90, 180, and 360 days later. RESULTS: Resting energy expenditure was significantly elevated after surgery (24% above predicted), peaking around day 10 after OLT, when it averaged 42% above predicted. A significant degree of hypermetabolism was still present at 6 months, but at 12 months measured resting energy expenditure was close to predicted values. Before surgery, measured total body protein was 82% of estimated preillness total body protein. During the first 10 days after OLT, a further 1.0 kg (10%) of total body protein was lost, mostly from skeletal muscle. Only 54% of this loss was restored by 12 months. Significant overhydration of the fat-free body was seen before OLT, and it was still present 12 months later. Although significant losses of body fat and bone mineral occurred during the early postoperative period, only body fat stores were restored at 12 months. Both subjective fatigue score and voluntary hand grip strength improved rapidly after OLT to exceed preoperative levels at 3 months. At 12 months grip strength was close to values predicted for these patients when well. Respiratory muscle strength improved less markedly and was significantly lower than predicted normal levels at 12 months. CONCLUSIONS: Before surgery, these patients were significantly protein-depleted, overhydrated, and hypermetabolic. After surgery, the period of hypermetabolism was prolonged, restoration of body protein stores was gradual and incomplete, and respiratory muscle strength failed to reach expected normal values. Our measurements indicate that OLT does not normalize body composition and function and imply that a continuing metabolic stress persists for at least 12 months after surgery.

Adolescent↗
PubMed2000

Combination low-dose hepatitis B immune globulin and lamivudine therapy provides effective prophylaxis against posttransplantation hepatitis B.

Although antiviral prophylaxis with lamivudine monotherapy appears to reduce post-liver transplantation recurrence of hepatitis B virus (HBV) infection, breakthrough infections occur in at least 20% of the patients because of the development of drug resistance. Combined lamivudine and intravenous hepatitis B immune globulin (HBIG) therapy (10,000-IU doses) may reduce this risk, but its use is limited by cost ( approximately US $45,000/yr) and availability. We report the experience at liver transplant centers in Australia and New Zealand in which lamivudine has been used in combination with much lower doses of HBIG than used in conventional HBIG prophylaxis. Lamivudine, 100 mg/d, was administered to hepatitis B surface antigen (HBsAg)-positive candidates on listing for transplantation and was continued posttransplantation. HBIG, 400 or 800 IU, was administered intramuscularly (IM) daily for 1 week from transplantation and monthly thereafter. Thirty-seven HBsAg-positive patients underwent transplantation using this protocol. Thirty-six of these patients were HBV DNA positive by polymerase chain reaction (PCR) or hybridization assay. Thirty-four patients had chronic HBV, 2 patients had hepatitis B and C, and 1 patient had hepatitis B, C, and D. Five patients died within 1 month of transplantation and are not included in the analysis. Mean follow-up in the remaining 32 patients was 18.4 months (range, 5 to 45 months). Treatment was well tolerated, with no significant adverse events. Thirty-one of 32 patients were HBsAg negative, and all 32 patients were HBV DNA negative by PCR at latest follow-up. The cost of treatment was US $967 for lamivudine and between $2,290 and $4,480/yr for IM HBIG. Lamivudine and low-dose HBIG treatment prevents posttransplantation recurrence of hepatitis B and is likely to be more cost-effective than high-dose HBIG regimens.

Adult↗
PubMed1999

Antibodies to hepatitis C virus envelope proteins correlate with hepatitis C viraemia after liver transplantation.

BACKGROUND: Liver transplant recipients for hepatitis C virus (HCV)-related cirrhosis usually remain anti-HCV-seropositive after transplantation. The aim of this study was to characterize, longitudinally, the profile of HCV-specific antibodies and cryoglobulins in liver transplant recipients with recurrent HCV infection. METHODS: Serial serum samples were collected prospectively before, at 1 month after, and at 12 months after transplantation for HCV cirrhosis in 30 patients infected with genotype 1. The antibodies against HCV envelope proteins (E1 and E2) were quantitated by enzyme-linked immunosorbent assay and antibodies against core, E2/hypervariable region I (HVRI), NS3, NS4, and NS5A antigens by a line immunoassay. Sera were also tested for cryoglobulins. RESULTS: The titer of each anti-HCV antibody had fallen at 1 month after transplantation (P<0.05) with the exception of anti-E1 levels, which had risen in 16 patients with acute hepatitis C at that time (P=0.01). Anti-E1 and anti-E2 titers, but not antibodies against other HCV antigens, increased to pre-transplantation levels or higher at 12 months, which correlated with serum HCV RNA levels. Cryoglobulinemia was present in nine patients after transplantation (30%) and was associated with lower anti-E1 levels (P=0.04) and more severe graft damage. CONCLUSIONS: The early increase in antibodies to HCV envelope proteins in correlation with viremia suggests that the envelope-specific humoral immune response may be directly stimulated by HCV replication. Anti-E1 levels may be a useful marker in monitoring patients with recurrent HCV infection.

Cryoglobulins↗
PubMed1998

A randomized study comparing ribavirin and interferon alfa monotherapy for hepatitis C recurrence after liver transplantation.

Hepatitis C virus (HCV) infection usually recurs after orthotopic liver transplantation (OLT), and most patients develop graft damage. This study compared the efficacy of interferon alfa (IFN-alpha) and ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft. Thirty OLT recipients with chronic hepatitis C were randomized to receive either IFN-alpha (3 MU three times a week) or ribavirin (up to 1.2 g daily) for 24 weeks. Virological, biochemical, and histological responses to treatment were assessed. Twenty-eight patients completed the treatment regimen, two ribavirin-treated patients being withdrawn because of severe hemolysis. Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin (93%) and 6 of 14 patients receiving IFN-alpha (43%; P=.01). Lobular inflammation was reduced in 9/14 ribavirin-treated (64%) and 3 of 14 IFN-alpha-treated patients (21%; P=.05), each of whom had a biochemical response. However, the total histological activity index did not improve in either the interferon (P=.43) or the ribavirin (P=.96) group. Posttreatment viremia levels were significantly reduced in IFN-alpha-treated (P=.05) but not in ribavirin-treated (P=.88) patients. Hemolysis occurred in all ribavirin-treated patients, with serum hemoglobin decreasing to < 10 g/dL in 50%. Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment (P=.02 and P=.004, respectively). We concluded that in patients with chronic hepatitis C after OLT, IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation, but not the total histological activity index. These findings provide a rationale for combination therapy in the post-OLT setting, although patients must be carefully monitored for hemolysis.

Adult↗
PubMed1997

Comparison of a new quantitative cytomegalovirus DNA assay with other detection methods.

OBJECTIVE: We assessed a new cytomegalovirus (CMV) DNA hybridization assay. We also compared the assay with other currently used assays to determine its use in the early detection of active CMV infection. PATIENTS AND METHODS: Sequential whole blood samples collected from 109 patients who had undergone orthotopic liver transplantation were tested using the Murex hybrid capture system, cell culture, antigen detection, and serology. Liver biopsies performed during the study period for graft dysfunction in 84 patients were examined for histological features of CMV hepatitis. The biopsies were also immunostained for the presence of CMV antigens. RESULTS: Fifteen patients developed clinically significant CMV disease (CMV syndrome in six patients and CMV hepatitis in nine patients, including two patients with disseminated CMV disease). In all 15, CMV DNA was detected by the hybrid capture assay between 1 and 20 days before other CMV assays. Fourteen of the 15 patients had CMV DNA levels greater than 50 pg/ml; the other patient had a value of 48 pg/ml. Of the remaining 94 patients with no evidence of CMV disease, 86 were negative by the hybrid capture assay and 8 were positive; all but one patient had values less than 50 pg/ml. DNA levels fell rapidly in all patients during antiviral therapy. CONCLUSION: Unlike conventional CMV detection methods, this hybridization assay is an early predictor of clinically significant CMV infection after liver transplantation and also provides quantitation of viral load, allowing monitoring of antiviral therapy.

Antibodies, Viral↗
PubMed1996

Long-term outcome of hepatitis C infection after liver transplantation.

BACKGROUND: End-stage cirrhosis related to hepatitic C virus (HCV) is a common reason for liver transplantation, although viremia ia known to persist in most cases. We investigated the impact of persistent HCV infection after liver transplantation on patient and graft survival and the effects of the HCV genotype and the degree of HLA matching between donor and recipient on the severity of recurrent hepatitis. METHODS: A group of 149 patients with HCV infection who received liver transplants between January 1982 and April 1994 were followed for a median of 36 months; 623 patients without HCV infection who underwent liver transplantation for end-stage chronic liver disease were used as a control group. A total of 528 liver-biopsy specimens from the HCV-infected recipients were reviewed, including 82 obtained one year after transplantation as scheduled and 39 obtained at five years as scheduled. In addition, biopsy specimens were obtained from 91 of the HCV-negative patients five years after transplantation. RESULTS: Cumulative survival rates for the 149 patients with HCV infection were 79 percent after one year, 74 percent after three years, and 70 percent after five years, as compared with rates of 75 percent, 71 percent, and 69 percent, respectively, in the HCV-negative transplant recipients (P=0.12). Of the 130 patients with hepatitis C infection who survived more than 6 months after transplantation, 15 (12 percent) had no evidence of chronic hepatitis on their most recent liver biopsy (median followup, 20 months), 70 (54 percent) had mild chronic hepatitis (median, 35 months), 35 (27 percent) had moderate chronic hepatitis (median, 35 months), and 10 (8 percent) had cirrhosis (median, 51 months). Graft loss occurred after a median of 303 days in 27 of the 149 patients, including 5 with HCV-related cirrhosis and 3 with HCV-related cholestatic hepatitis. Infection with HCV genotype 1b was associated with more severe graft injury, whereas the primary immunosuppressive regimen used and the extent of HLA mismatching between donors and recipients had no significant effect on this variable. CONCLUSIONS: After liver transplantation for HCV-related cirrhosis, persistent HCV infection can cause severe graft damage, and such damage is more frequent in patients infected with HCV genotype 1b than with other genotypes. After five years, the rates of graft and overall survival are similar between patients with and those without HCV infection.

Adult↗
PubMed1996

A longitudinal analysis of hepatitis C virus replication following liver transplantation.

BACKGROUND & AIMS: The pathogenesis of graft injury in liver transplant recipients with recurrent hepatitis C virus (HCV) infection remains poorly understood. In this study, the relationship between HCV replication, genotype, and the evolution of graft damage was investigated. METHODS: HCV RNA was quantified in 184 protocol sera from 25 patients transplanted for HCV cirrhosis. HCV isolates were genotyped, and hepatic expression of core and NS4 antigens was sought in protocol allograft biopsy specimens. RESULTS: Acute lobular hepatitis was accompanied by a steep increase in HCV RNA levels and the appearance of core and NS4 antigens in the graft. Methylprednisolone treatment for acute rejection led to a 4-100-fold increase in serum HCV RNA. At the end of follow-up, HCV RNA levels were 3-112 times pretransplant levels and were higher in patients with more severe hepatitis. Progressive liver damage developed in 7 of 14 patients with HCV genotype 1b and in 1 of 11 patients infected with other genotypes (P = 0.03). CONCLUSIONS: Peak viremia levels and the initial detection of HCV antigens in hepatocytes suggests increased viral replication at the time of acute HCV hepatitis in the graft. Genotype 1b and higher viremia levels were associated with more severe chronic graft damage.

Adult↗
PubMed1995

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↗
PubMed1992

Upper gastrointestinal endoscopy in patients with human immunodeficiency virus infection: is it worthwhile?

AIM: To determine the diagnostic accuracy of upper gastrointestinal endoscopy in a selected group of patients with HIV infection, who had severe symptoms unresponsive to empirical treatment. METHOD: We reviewed all patients with HIV infection, who had undergone upper gastrointestinal endoscopy at Auckland Hospital. Specific diagnoses were based on the endoscopic appearances and on the histological and microbiological examination of endoscopic biopsies taken from the oesophagus, stomach and duodenum. RESULTS: A definitive diagnosis was reached in 16 of the 21 patients endoscoped, of whom 13 had a good clinical response to treatment. The median survival was three months. The most common diagnosis was oesophageal candidiasis seen in six patients, all of whom responded to treatment with a median survival of six months. Invasive cytomegalovirus gastrointestinal disease was seen in three patients, none of whom had positive blood cultures for cytomegalovirus. All responded to intravenous ganciclovir. Three patients with severe diarrhoea had opportunistic infection of the small bowel. All three had advanced AIDS with a median survival of less than one month. CONCLUSION: Upper gastrointestinal endoscopy has a high diagnostic yield in patients with HIV infection with oesophageal symptoms which fail to respond to antifungal therapy, or with severe weight loss and diarrhoea and it should be considered in these patients because excellent palliation may be possible.

AIDS-Related Opportunistic Infections↗
PubMed1992

Neurological disease in patients with human immunodeficiency virus infection.

We followed prospectively all patients with HIV infection admitted to the infectious diseases ward at Auckland Hospital over a seven month period. Neurological manifestations of HIV infection were the primary reason for admission in 18 of the 55 patients (33%). Diagnoses were usually presumptive, based on history, clinical findings, radiological appearances and response to empirical therapy. Eight patients had cerebral toxoplasmosis, three primary cerebral lymphoma, two cytomegalovirus retinitis, two HIV neuropathy, one cryptococcal meningitis, one HIV encephalopathy, and one HIV meningitis. Another patient with HIV infection was admitted to the neurology ward at Auckland Hospital with HIV myelopathy during the same seven month period. The median survival of the patients treated for presumptive toxoplasmosis was 7.5 months. Only two patients had not developed AIDS, one having HIV meningitis and the other HIV myelopathy, and in both, symptoms resolved spontaneously with no relapse at one year follow up. The spectrum of neurological manifestations of HIV infection is wide. Investigations to determine the most likely diagnosis are indicated and specific therapy may lead to both excellent palliation and prolonged survival.

HIV Infections↗
PubMed1992

Colonoscopy in unexplained lower gastrointestinal bleeding.

Two hundred and forty patient with unexplained gastrointestinal blood loss underwent colonoscopy. Significant lesions which were thought to be likely causes of bleeding were identified in 98 patients, ie, 41% of total, which included active colitis in 9%, large polyps in 10% and colorectal cancer in 12% of patients. Of the cancers found at colonoscopy, 64% were Dukes A or B. This study confirms the role of colonoscopy in the investigation of unexplained chronic lower gastrointestinal bleeding.

Adult↗
PubMed1992

Fulminant hepatic failure in a young mother.

We report the case of a mother who developed fulminant hepatic failure with hypoglycaemia, coagulopathy, Grade III hepatic encephalopathy, two days after the delivery of her fourth child. She had complained of pruritus for the final two weeks of pregnancy. She received supportive medical management within a critical care unit, and the hepatic failure resolved completely within 48 hours. Liver biopsy confirmed the diagnosis of acute fatty liver of pregnancy. This case is unusual in that this patient deteriorated markedly following delivery, at a time when spontaneous recovery is normally expected.

Adult↗