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Biomedical subjects

E M Yoshida

Publications and source records attributed to E M Yoshida.

At least 19 recordsLinked to original sources
PubMed2006

Liver test abnormalities in multiple sclerosis: findings from placebo-treated patients.

The risk of an abnormal liver test in 813 patients with multiple sclerosis or clinically isolated syndrome enrolled in placebo arms of clinical trials was greater than expected for alanine aminotransferase (ALT) (relative risk [RR] 3.7; 95% CI: 2.3 to 6.0) and aspartate aminotransferase (AST) (RR 2.2; 95% CI: 1.3 to 3.6), although not alkaline phosphatase (AP) or total bilirubin, at first presentation. Abnormal test results were associated with higher body mass index (ALT only), male gender (ALT only), and a relapsing-remitting (vs secondary-progressive) course (ALT and AST only).

Adolescent↗
PubMed2006

Peginterferon alfa-2a (40KD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy.

BACKGROUND: The management of patients with chronic hepatitis C who have relapsed or failed to respond to interferon based therapies is an important issue facing hepatologists. AIMS: We evaluated the efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in this population by conducting a multicentre open label study. PATIENTS: Data from adults with detectable serum hepatitis C virus (HCV) RNA who had not responded or had relapsed after previous conventional interferon or conventional interferon/ribavirin combination therapy were analysed. METHODS: Patients were retreated with peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 800 mg/day for 24 or 48 weeks at the investigators' discretion. The study was conceived before the optimal dose of ribavirin (1000/1200 mg/day) for patients with genotype 1 was known. The primary endpoint was sustained virological response (SVR), defined as undetectable HCV RNA (<50 IU/ml) after 24 weeks of follow up. The analysis was conducted by intention to treat. RESULTS: A total of 312 patients (212 non-responders, 100 relapsers) were included. Of these, 28 patients were treated for 24 weeks and 284 for 48 weeks. Baseline characteristics between non-responders and relapsers were similar although more non-responders had genotype 1 infection (87% v 69%). Overall SVR rates were 23% (48/212) for non-responders and 41% (41/100) for relapsers. When data were analysed by genotype, SVR rates were 24% (61/253) in genotype 1 and 47% (28/59) in genotype 2/3. CONCLUSIONS: These results in a large patient cohort demonstrate that it is possible to cure a proportion of previous non-responders and relapsers by retreating with peginterferon alfa-2a (40KD) plus ribavirin.

Adult↗
PubMed2006

Treating chronic hepatitis C with pegylated interferon alfa-2a (40 KD) and ribavirin in clinical practice.

BACKGROUND: Pegylated interferon alfa-2a (40 KD) plus ribavirin therapy induces sustained virological response rates up to 63% in randomized-controlled trials. AIM: To conduct a prospective open-label programme to examine the efficacy and safety of this therapy in routine clinical practice. METHODS: Treatment-naive patients with chronic hepatitis C received, at the discretion of the investigator, pegylated interferon alfa-2a 180 microg/week + ribavirin 800 mg/day for 24 or 48 weeks. In total, 508 patients were enrolled [334 non-cirrhotic; 174 cirrhotic (defined as stage F3 and F4)]. RESULTS: In genotype 1 patients treated for 48 weeks, sustained virological response rates were 41% in non-cirrhotics and 34% in cirrhotics. Sustained virological response rates in genotype 2 or 3 non-cirrhotics were 79% (24 weeks) and 72% (48 weeks). Corresponding values for cirrhotic genotype 2/3 were 66% and 44%. The negative predictive value of an early virological response at week 12 was 94%. Predictive factors for sustained virological response on multivariate analysis were genotype (2/3 vs. 1), low viral load and degree of fibrosis. Rates of serious adverse events (<or=5%) and adverse events inducing withdrawal (<or=8%) were comparable with the phase III trials. CONCLUSION: Efficacy and safety of pegylated interferon alfa-2a + ribavirin in clinical practice is comparable with results of randomized-controlled trials.

Adult↗
PubMed2006

Interferon-based combination anti-viral therapy for hepatitis C virus after liver transplantation: a review and quantitative analysis.

Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) is universal. However, the efficacy, tolerability and safety of combination interferon and ribavirin (IFN-RIB) or peginterferon and ribavirin (PEG-RIB) anti-viral therapies post-LT are uncertain. We performed a comprehensive search of major medical databases (1980-2005) and conference proceedings (1996-2005). The main outcome measure was sustained virological response (SVR, undetectable HCV RNA) at 6 months. Summary estimates were calculated using random-effects models. Twenty-seven IFN-RIB and 21 PEG-RIB studies were included. IFN-RIB was associated with a pooled SVR rate of 24% (95% CI, 20-27%), while PEG-RIB was associated with an SVR rate of 27% (23-31%). Pooled discontinuation rates were 24% (21-27%) with IFN-RIB and 26% (20-32%) with PEG-RIB. The pooled rate of acute graft rejection was 2% (1-3%) with IFN-RIB and 5% (3-7%) with PEG-RIB. IFN-RIB and PEG-RIB therapies in HCV infection post-LT were associated with similar but overall low SVR and were poorly tolerated. The rate of acute rejection was small. The therapeutic advantage of PEG-RIB therapy observed in non-transplant chronic HCV infection appears to be attenuated post-LT. Clinical trials are needed to evaluate reasons for this post-transplant therapeutic disadvantage and to find strategies to ameliorate them.

Antiviral Agents↗
PubMed2005

Recurrent hepatocellular carcinoma after liver transplantation mimicking post-transplantation lymphoproliferative disorder.

Approximately 5% of patients with end-stage cirrhosis undergoing orthotopic liver transplantation have occult hepatocellular carcinoma. Careful follow up is required to detect recurrent tumour, and knowledge of the patterns of recurrence may avoid diagnostic confusion with other malignancies, such as post-transplantation lymphoproliferative disorder. This case report illustrates an unusual presentation of recurrent hepatocellular carcinoma in a 56-year-old man presenting with a para-aortic soft tissue mass, thought clinically and radiologically to represent lymphoma or post-transplantation lymphoproliferative disorder. This case demonstrates that recurrent hepatocellular carcinoma can present late after transplantation as retroperitoneal lymphadenopathy, and should alert physicians and radiologists to be aware of the radiological appearances of recurrence and of the need for early biopsy to avoid diagnostic confusion with other malignancies.

Carcinoma, Hepatocellular↗
PubMed2004

Hepatic abscesses after liver transplantation secondary to traumatic intrahepatic bile duct injuries in a cadaveric allograft donor.

We report the case of an ultimately successful liver transplant recipient whose post-transplant course was complicated by the early development of multiple abscesses in the graft. Post-transplant cholangiography identified multiple shear injuries to the second and third order intrahepatic bile ducts, originating from blunt trauma to the donor liver. Treatment was non-operative following recent reports of the successful management of intrahepatic bile duct injury in the stable trauma patient. This discussion adds to the limited literature available on the transplantation of injured donor livers, despite this being a relatively common practice. Further experience is needed in determining the appropriate criteria for the use of traumatized donor livers. Cholangiography carried out on the back table may help to determine if such injured livers are suitable for transplantation.

Aged↗
PubMed2002

SEN virus. A clinical review.

SEN-V is a newly discovered single-stranded DNA virus that is distantly related to TT virus. Eight genotypes of SEN-V, designated SEN-V: A to H, have been identified although it has been suggested that genotypes SEN-V: H & C as well as SEN-V: D & F be combined. SEN-V is clearly transmitted via transfusion of blood products and parenteral contact. It appears to have a world-wide distribution as it has been isolated in every country that has been studied including remote communities. Interest in SEN-V arises from initial reports that two SEN-V genotypes, SEN-V: D & H, were associated with post-transfusion non-A, non-E hepatitis. The focus of investigations of SEN-V and liver disease has been exclusively with these two genotypes. Although one study documented a clear temporal relation between post-transfusion SEN-V infection and NANE hepatitis, and found that over 90% of a small cluster of NANE hepatitis cases were associated with SEN-V, it is also clear that the majority of patients who acquire SEN-V do not suffer hepatitis. Furthermore, other studies have failed to find a significant difference in prevalence between SEN-V and etiologically known vs cryptogenic acute or chronic liver disease, cryptogenic hepatoma vs HBV & HCV-associated hepatoma and post-liver transplant biochemical abnormalities. Despite the fact that there is no consensus that SEN-V is a cause of liver disease, it does appear to be responsive to interferon-based therapy.

Journal Article↗
PubMed2001

Impaired exercise performance after successful liver transplantation.

BACKGROUND: Recipients of heart, lung, and kidney transplants have impaired peak exercise performance (peak Vo2 40% to 60% predicted, reduced anaerobic threshold [AT]) without evidence of ventilatory or cardiac limitations. The aim of this study was to determine whether similar exercise impairment occurs in liver transplant recipients. METHODS: We studied eight healthy liver transplant recipients (age 42+/-9 [SD] years, 6 male, 31+/-13 months posttransplant). Immunosuppression included FK506 or cyclosporine, azathioprine or mycophenolate mofetil, and prednisone. Subjects underwent lung function testing and cardiopulmonary exercise testing on a cycle ergometer. RESULTS: Peak exercise oxygen consumption (Vo2) was 22+/-8 ml/min/kg (66+/-20% predicted maximum). No subject demonstrated exercise desaturation or ventilatory limitation (peak minute ventilation 55+/-8% predicted maximum voluntary ventilation). Peak heart rate was 87+/-8% of predicted maximum. Early AT was evident (1.2+/-0.34 L/min, 48+/-11% predicted Vo2max). CONCLUSIONS: Liver transplant recipients exhibit impaired peak exercise performance similar to that observed after other solid organ transplants, possibly as a result of chronic deconditioning or myopathy related to immunosuppressive medications.

Adult↗
PubMed2001

A study of the pharmacokinetic profile of low-dose hepatitis B immune globulin in long-term liver transplant recipients for chronic hepatitis B infection.

Post-transplant protocols for hepatitis B (HBV) prophylaxis using high-dose intravenous hepatitis B immune globulin (10,000 IU) with or without lamivudine are commonly reported. Our centre has previously reported a low-dose intramuscular (i.m.) protocol and lamivudine with excellent results. There have been, however, no pharmacokinetic studies of i.m. hepatitis B immune globulin (HBIG) in this setting. The objective of this study was to determine the pharmacokinetic profile of i.m. HBIG in long-term post-liver-transplant recipients to determine a rational dosing protocol. Six stable liver transplant recipients receiving monthly i.m. HBIG injections for greater than one year were enrolled in this study. All patients had no detectable HBV DNA levels. HBIG titers (anti-HBs) were measured predose, then three times weekly for four weeks and then twice weekly until the serum HBIG titers were 100 IU/L or less. The pharmacokinetic parameters were calculated using noncompartment methods. The mean time to maximum concentration was 10.5 d (range 4-20 d) and the mean half-life was 20 d (range 13.5-23.5 d). Based on these pharmacokinetic parameters in stable long-term post-transplant patients, a rational dosing protocol was developed that allows for more appropriate utility of HBIG and improved patient convenience.

Area Under Curve↗
PubMed2001

A cross-sectional study of SEN virus in liver transplant recipients.

A new DNA virus, referred to as SEN virus (SEN V), has been isolated and is associated with blood-product transfusion and possibly Non A to Non E hepatitis. We performed a cross-sectional analysis of SEN V in liver transplant recipients at our center. Polymerase chain reaction was used to test for 2 genotypes of SEN V (SEN V:C/H and SEN V:D) in 58 unselected patients. Comparisons were made between SEN V--positive and SEN V--negative groups in terms of age, time posttransplantation, indications for transplantation, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and cytomegalovirus and Epstein-Barr virus status. Thirty of 58 transplant recipients (51.7%) were SEN V positive; 15.5% were positive for SEN V:C/H, 24.1% for SEN:D, and 12.1% for both strains. No significant differences were found based on primary indication for transplantation, including hepatitis C virus (HCV). Of the 14 of 21 patients with HCV seropositivity and HCV reinfection, 79% were positive for SEN V (P =.02). There was no difference in the proportion of patients with abnormal serum ALT and/or AST levels. A trend for the SEN V--positive group to have a greater mean ALT level (82 v 41 U/L; P =.067) was attributable to the subgroup with HCV recurrence because there was no difference in mean ALT levels (34.9 v 34.5 U/L; P =.968) in non--HCV-infected transplant recipients. Even in the subgroup (n = 14) with recurrent HCV, there was no statistically significant difference in mean ALT levels (140 v 105 U/L; P =.665). Age and cytomegalovirus or Epstein-Barr virus status were not significantly different between the 2 groups, but a significant difference in posttransplantation time was noted (16.8 v 32 months; P =.021). We conclude that SEN V is common among liver transplant recipients but does not appear to cause graft dysfunction as an isolated agent. There is a suggestion that SEN V may be associated with HCV recurrence, but we did not detect biochemical differences attributable to SEN V.

Alanine Transaminase↗
PubMed2001

Analysis of causes of death in liver transplant recipients who survived more than 3 years.

Few studies have examined causes of death in long-term survivors of orthotopic liver transplantation (OLT). We reviewed causes of death among 299 adult liver transplant recipients who survived more than 3 years after OLT at 2 centers. Thirty-eight of the 299 patients subsequently died. Nonhepatic causes accounted for 22 of 38 late deaths (58%). Death caused by malignancies occurred in 9 patients between 3.3 and 8.0 years after OLT. Eight patients died of cardiovascular complications. The 6 patients who died of myocardial infarction had risk factors for coronary artery disease. Hepatic failure caused by recurrent liver disease or chronic rejection accounted for 16 of 38 late deaths (42%). These 16 patients were younger than patients who died of nonhepatic complications (mean ages, 50.7 v 62.1 years; P =.001). However, the mean interval between OLT and death was similar among patients who died of nonhepatic versus hepatic causes. Nine patients had recurrent liver disease leading to death, and 8 of 9 patients had recurrent chronic hepatitis C virus (HCV) infection. Chronic rejection resulting in graft failure and death occurred in 7 patients. In summary, de novo malignancies and cardiovascular complications accounted for more than half the late deaths. Patients who died of nonhepatic causes were significantly older than patients who died of hepatic causes. Chronic rejection and recurrent HCV infection accounted for the majority of hepatic causes of death. With longer follow-up, graft failure resulting from recurrent HCV infection will become the major cause of death in late survivors.

Adult↗
PubMed2001

Obstacles to residents' conducting research and predictors of publication.

Internal medicine residents at one school identified barriers to and predictors of publishing their research. Insufficient time was the key obstacle to completing research. Residents with previous research experience, senior residents, and men were more likely to publish.

Attitude of Health Personnel↗
PubMed2001

Primary protein-losing enteropathy in anti-double-stranded DNA disease: the initial and sole clinical manifestation of occult systemic lupus erythematosus?

Hypoalbuminemia and generalized edema is a common clinical problem and the etiology is usually clear: cirrhosis, nephrotic syndrome, primary gastrointestinal disorders, malnutrition, etc. We present a 23-year-old previously healthy woman of Korean background who presented with generalized edema and a serum albumin of 9 g/L (normal, 35-45 g/L). Intensive investigations failed to reveal liver, renal, or inflammatory gastrointestinal mucosal disease. The antinuclear antibody was positive at a titer of 1:80, and extractable nuclear antigens were positive for SSA/anti-Ro. Anti-double-stranded DNA was markedly elevated at 4.6 kU/L (normal, 0-2.0 kU/L). A technetium 99M-labeled albumin study revealed a protein-losing enteropathy, despite normal histologic full-thickness jejunal biopsies. A diagnosis of occult systemic lupus erythematosus resulting in increased intestinal vascular permeability was made. The hypoalbuminemia remained in long-term remission after the initiation of induction and maintenance immunosuppression.

Adult↗