Search PubMed⌕ Search

Biomedical subjects

E M Yoshida

Publications and source records attributed to E M Yoshida.

At least 37 records · Page 2Linked to original sources

Post-transplant diabetic ketoacidosis--a possible consequence of immunosuppression with calcineurin inhibiting agents: a case series.

Post-transplant diabetes mellitus, a complication due to corticosteroids and the calcineurin inhibitors, cyclosporine and tacrolimus (FK506), is commonly regarded as a form of type-2 (adult-onset) diabetes mellitus. Diabetic ketoacidosis, which requires relative insulin deficiency to impair fatty acid metabolism, is a complication of type-1 diabetes mellitus. We report three patients who presented with diabetic ketoacidosis post-transplant. All three patients presented with severe hyperglycemia, significant ketosis and metabolic acidosis of variable severity. One patient was a renal transplant recipient on a cyclosporine-based regimen. The other two patients were liver transplant recipients receiving either cyclosporine or tacrolimus-based immunosuppression. Both of the liver transplant recipients were found to have moderate to high serum levels of calcineurin inhibitors on presentation. The liver recipient on cyclosporine (Neoral) had a 4 hour post-dose level of 388 ng/ml and the patient on tacrolimus was found to have a trough level of 21.2 ng/ml. Our experience suggests that post-transplant diabetes mellitus, in association with calcineurin inhibition, may result in ketoacidosis either secondary to relative beta cell dysfunction, peripheral insulin resistance, or a combination of the two effects. Post-transplant diabetes mellitus can be an atypical form of adult-onset diabetes with features of both type I and type II diabetes mellitus.

Adult↗

Correlation between physiological assessment and outcome after liver transplantation.

BACKGROUND: Critical shortages of organ donors for transplantation require appropriate utilization of this scarce resource. The purpose of this study was to assess whether use of physiological parameters of preliver transplant recipients is helpful in determining eventual outcome. METHODS: Between October 1989 and June 1999, 215 liver transplants were performed on 199 patients at the Vancouver Hospital nad Health Sciences Centre. Thirty-one patients undergoing transplantation between May 1993 and June 1994 were retrospectively evaluated to obtain a minimum 5-year follow-up. Variables examined included pretransplant activation status (status 1, at home; status 2, hospitalized; status 3, admitted to intensive care; status 4, mechanical ventilation), simplified acute physiological score (SAPS), Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II, and APACHE III scores at the time of transplantation. The scores were correlated to posttransplant mortality and functional outcome. RESULTS: The 5-year mortality for status 1 patients was 14.3% versus 30% for patients listed as status 2 or greater (P = not significant). There were no significant differences in any of the physiological scoring assessments with regard to posttransplant mortality or functional assessment. Of the surviving patients, 18 of 22 who were employed, in school, or active at home pretransplant returned to their pretransplant activity. CONCLUSIONS: Detailed physiological scoring systems are no more accurate in predicting outcome after liver transplant than current listing status parameters.

APACHE↗

Genotypic succession of mutations of the hepatitis B virus polymerase associated with lamivudine resistance.

BACKGROUND/AIMS: Hepatitis B mutant strains of virus emerging during treatment with the nucleoside analog lamivudine are being increasingly recognized. In the majority of lamivudine-resistant isolates the mutations have been reported to occur within the YMDD motif of the viral polymerase, either as a single mutation M552I or as M552V concomitant with L528M. We analyzed the time course and genetic succession pattern during the emergence of lamivudine resistance. METHODS: Seven patients with breakthrough viremia in the setting of chronic hepatitis (n=5) or recurrent HBV after liver transplantation (n=2) were investigated. Pre- and post-breakthrough serum samples were evaluated by single- or second-round PCR amplification and sequencing analysis. RESULTS: Genotypic succession of the virus populations was observed to occur from M552I to M552I/L528M (n=2) and from L528M to M552V/L528M (n=1). The double mutations M552I/L528M (n=4) or M552V/L528M (n=2) were found in six out of seven patients, and represented the stable virus populations throughout the follow-up period. Breakthrough viremia was not associated with the single L528M mutation. The mean duration of uninterrupted treatment with lamivudine until breakthrough was 422 days (range 182-642) and was longer in the setting of chronic hepatitis B than in recurrent hepatitis B after liver transplantation. HBV DNA levels after breakthrough were lower than pretreatment levels in the majority of patients with chronic hepatitis but higher after liver transplantation. CONCLUSION: Our observations show that the virus populations conferring resistance to lamivudine can evolve from single to double mutations at amino acid 552 and 528 of the HBV polymerase, and that M552I/ L528M or M552V/L528M seem to be the predominant mutations arising during long-term antiviral therapy with lamivudine.

Adult↗

De novo acute hepatitis B infection in a previously vaccinated liver transplant recipient due to a strain of HBV with a Met 133 Thr mutation in the "a" determinant.

UNLABELLED: De novo HBV infection post-liver transplantation (LT) from an anti-HBc seropositive donor rarely presents as acute failure. We report a 42-year-old Caucasian female, HBsAg and anti-HBc seronegative, with primary biliary cirrhosis who received an allograft from a HBsAg negative, anti-HBc seropositive donor. The patient, previously vaccinated years pre-LT, was re-vaccinated against HBV and 1 year post-LT had an anti-HBs titre of 256 IU/l. Two years post-LT, elevated serum aminotransferases and worsening liver function with an INR of 2.0 developed. The HBsAg became positive, anti-HBs undetectable and serum HBV-DNA >2000 pg/ml by hybridisation assay. Liver biopsy revealed significant ballooning degeneration, piecemeal necrosis and positive immunostaining for HBsAg. Progressive liver failure developed followed by sepsis and terminal multi-organ failure. Subsequent analysis of the predominant HBV strain revealed mutations in the "a" determinant: Met 133 Thr (codon change ATG to ACG) and Asn 131 Thr. CONCLUSION: ' Acute de novo HBV infection from an anti-HBc sero-positive donor may occur long after LT despite protective anti-HBs titres post-vaccination secondary to the emergence of "a" determinant mutated strains of HBV.

Acute Disease↗

Indications for liver transplantation in British Columbia's Aboriginal population: a 10-year retrospective analysis.

OBJECTIVES: To study the indications for liver transplantation among British Columbia's First Nation population. MATERIALS AND METHODS: A retrospective analysis of the British Columbia Transplant Society's database of Aboriginal and non-Aboriginal liver transplant recipients from 1989 to 1998 was undertaken. For primary biliary cirrhosis (PBC), the transplant assessment database (patients with and without transplants) was analyzed using a binomial distribution and compared with published census data regarding British Columbia's proportion of Aboriginal people. RESULTS: Between 1989 and 1998, 203 transplantations were performed in 189 recipients. Fifteen recipients were Aboriginal (n=15; 7.9%). Among all recipients, the four most frequent indications for liver transplantation were hepatitis C virus (HCV) infection (n=57; 30.2%), PBC (n=34; 18.0%), alcohol (n=22; 11.6%) and autoimmune hepatitis (n=14; 7.4%). Indications for liver transplantation among Aboriginal people were PBC (n=8; 53.3%; P<0.001 compared with non-Aboriginal people), autoimmune hepatitis (n=4; 26.67%; P=0.017), acute failure (n=2; 13.3%) and HCV (n=1). Among all patients referred for liver transplantation with PBC (n=43), 29 (67.44%) were white and 11 (25.6%) were Aboriginal. A significant difference was found between the proportion of Aboriginal people referred for liver transplantation and the proportion of Aboriginal people in British Columbia (139,655 of 3,698,755 [3.8%]; 1996 Census, Statistics Canada) (P<0.001). CONCLUSIONS: Aboriginal people in British Columbia are more likely to be referred for liver transplantation with a diagnosis of PBC but are less likely to receive a liver transplant because of HCV or alcohol than are non-Aboriginal people.

British Columbia↗

Racial differences between solid organ transplant donors and recipients in British Columbia: a five-year retrospective analysis.

BACKGROUND: We attempted to determine whether significant racial differences exist between organ donors and transplant recipients in British Columbia, and whether differences exist between individual organ transplant programs (lung, heart, kidney, liver, and pancreas). The design of the study was a retrospective review. METHODS: We used the database of the British Columbia Transplant Society, a provincial agency, for the years 1992 to 1997 inclusive. The outcome measures were a comparison of racial characteristics of organ donors and transplant recipients collectively and by individual organ transplant program. RESULTS: There were 236 organ donors and 766 transplant recipients. Comparing racial groups between donors and recipients, Caucasians contributed the most donors (93.2%) but received proportionately fewer organs (73.4%, P<0.000001). Orientals donated 3.4% of all organs but constituted 14.4% of all recipients (P<0.00001). Non-Oriental, non-Caucasians (predominantly Asian Indians and Native Aboriginals) constituted 3.4% of all donors and 12.2% of all recipients (P=0.0001). Among the individual organ transplant programs, lung, heart, and pancreas recipients were predominantly Caucasian (148 of 156 recipients). Oriental recipients were more likely to be kidney recipients (19.8% of all kidney recipients) compared with all Oriental recipients (P<0.000001). Likewise, Asian Indians were more likely to be kidney recipients (7.2% of all kidney recipients) compared with all Asian Indian recipients (P<0.0001). Native Aboriginals, however, were more likely to be liver allograft recipients (8.3% of all liver transplants) than nonliver allograft recipients (P=0.017). CONCLUSIONS: In British Columbia, disparity exists between Oriental and non-Oriental, non-Caucasian donors and recipients. Orientals and Asian Indians were more likely to be kidney graft recipients than nonkidney graft recipients, whereas Native Aboriginal recipients seemed more likely to have undergone liver transplantation.

Asian People↗

Liver transplantation for chronic hepatitis B infection with the use of combination lamivudine and low-dose hepatitis B immune globulin.

Current protocols for prophylaxis against allograft reinfection after liver transplantation for chronic hepatitis B virus (HBV) infection include the administration of large doses of hepatitis B immune globulin (HBIG), with considerable associated economic costs. Monotherapeutic prophylaxis with lamivudine has been complicated by the development of resistant strains of HBV. We studied the effectiveness of a posttransplantation prophylaxis protocol using combination lamivudine and low-dose HBIG in 7 consecutive patients with chronic HBV infection, 4 of whom were serum HBV DNA positive before pretransplantation lamivudine therapy. All patients were serum HBV DNA negative at transplantation and received lamivudine, 100 mg/d, posttransplantation. HBIG, 2170 IU, was administered intramuscularly intraoperatively and daily for 14 days. Maintenance HBIG therapy consisted of 2170 IU intramuscularly twice weekly, tapered to every 2 to 4 weeks by 12 months posttransplantation. Target serum HBIG (HBV surface antibody) titers were less than 500 IU/L for 6 months, then greater than 300 IU/L until 12 months posttransplantation. Induction serum HBIG titers were determined daily in 5 patients, and both serum HBIG and hepatitis B surface antigen were determined every 4 weeks in all patients. One patient died 61 days posttransplantation; the surviving patients (n = 6) were followed up for a mean of 532 days (range, 395 to 648 days). No patient has developed allograft reinfection. In the induction period, a target HBIG titer of greater than 500 IU/L was not achieved until a mean of 6.8 days (range, 5 to 10 days). In the maintenance period, all patients achieved the target HBIG titer. This suggests combination lamivudine and low-dose HBIG is effective in preventing allograft reinfection by HBV.

Follow-Up Studies↗

Hepatitis C infection and B-cell non-Hodgkin's lymphoma in British Columbia: a cross-sectional analysis.

OBJECTIVES: To determine the prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (NHL) in British Columbia. DESIGN: A cross-sectional analysis. SETTING: The British Columbia Cancer Agency (BCCA), a Canadian provincial tertiary oncology referral center. SUBJECTS: Consecutive patients with B-cell NHL registered onto the BCCA lymphoma database in 1996 and part of 1997 and a control group of patients with T-cell NHL registered on the database from 1995 through 1997. Patients with HIV infection were excluded from the analysis. A second control group (n = 1085) consisted of health-care workers tested for HCV infection following a needle-stick injury. INTERVENTIONS: Stored sera from patients with B-cell NHL (n = 88) and T-cell NHL (n = 37), identified from the database, were tested for the presence of HCV infection with commercially available serologic tests. MAIN OUTCOME MEASURES: HCV seropositivity in the B-cell lymphoma group compared to the control groups (T-cell NHL and health-care workers). RESULTS: 2.3% of the B-cell NHL group, none of the T-cell NHL group and 1% of the health-care worker control group were positive for HCV infection. These results were not statistically significantly different. CONCLUSION: Patients in British Columbia with B-cell NHL do not have an increased prevalence of HCV infection. These data suggest that the lymphotrophism of HCV may differ by regional, racial and genotypic variations around the world.

Adult↗

Assessment of immunologic status of liver transplant recipients by peripheral blood mononuclear cells in response to stimulation by donor alloantigen.

OBJECTIVE: To determine whether there is a role for assessing peripheral blood mononuclear cell (PBMC) cytokine patterns as a means of measuring the immunologic and clinical status of liver transplant recipients. SUMMARY BACKGROUND DATA: The role of assessing cytokine patterns in the prediction of clinical graft rejection or acceptance remains unclear. The purpose of this study was to examine the cytokine profiles of PBMC stimulated in vitro with donor alloantigen and to correlate prospectively the data with clinical assessment of graft status in orthotopic liver transplant (OLT) recipients. METHODS: PBMCs from OLT recipients were examined for proliferation and cytokine mRNA expression after stimulation by donor alloantigen, third-party alloantigen, or phytohemagglutinin (PHA). mRNA extracted from PBMC was amplified by reverse transcriptase-polymerase chain reaction with oligospecific primer pairs for interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN) gamma, tumor necrosis factor (TNF) alpha and transforming growth factor (TGF) beta. Results were prospectively correlated with each patient's allograft status. RESULTS: Increased IL-4 and TGF-beta and decreased IL-2, IFNgamma, and TNF-alpha mRNA expression by PBMCs in response to donor alloantigen stimulation predicted immunologic graft stability over a minimum 60-day interval compared with mRNA expression of PBMCs from patients with established rejection or those who experienced a rejection episode within a 30-day period (p < 0.05). Stimulation of recipient PBMCs with third-party alloantigens or PHA yielded similar but less specific results. PBMC proliferation to varying antigenic stimulation did not correlate with clinical graft status, nor did cytokine production by unstimulated PBMC. CONCLUSIONS: Prospective assessment of cytokine expression by PBMC from OLT recipients in response to stimulation by donor alloantigen is helpful for predicting the clinical status of the allograft and may be useful in the development of more precise immunologic monitoring protocols.

Adult↗

Post-surgical shunt hepatopulmonary syndrome in a case of non-cirrhotic portal hypertension: lack of efficacy of shunt reversal.

Hepatopulmonary syndrome, a consequence of significant liver disease and portal hypertension, is thought to be secondary to the effects of vasoactive substances, normally inactivated in the liver, on the pulmonary vasculature. We report a patient with preserved hepatic function who underwent a decompressive surgical porto-systemic shunt for non-cirrhotic portal hypertension. This patient developed hepatopulmonary syndrome with dyspnoea and oxygen desaturation 2 years post-surgical shunt. Over the next 7 years, the patient's respiratory function became increasingly impaired although hepatic function remained preserved. Because of the hypothesized role of porto-systemic shunting in the aetiology of this syndrome, the surgical shunt was successfully reversed angiographically. No improvement in dyspnoea or oxygen saturation occurred and liver transplantation was undertaken. Six months post-transplant, the patient has decreased his oxygen requirements and is free of dyspnoea. Our experience supports the causal role of porto-systemic shunting in the pathogenesis of hepatopulmonary syndrome but suggests that merely decreasing the extent of porto-systemic shunting is not beneficial. Liver transplantation remains the only reliable therapeutic modality available to these patients.

Adult↗

Coexisting carcinoid tumors in familial adenomatous polyposis-associated upper intestinal adenomas.

Upper gastrointestinal polyps and extraintestinal tumors are well recognized in association with familial adenomatous polyposis (FAP). Although carcinoid tumors have been reported in association with sporadic colonic neoplasms and ulcerative colitis, to date, carcinoids have not been reported in association with FAP. We report a patient with FAP who has recurrent carcinoid tumors located at the bases of duodenal adenomas. The genetic basis of carcinoid neoplasms is still uncertain. This report may represent the clinical effect of the APC gene mutation on the enterochromaffin cell line manifesting as recurrent carcinoid tumors in physical association with intestinal adenomas. Future genetic analysis and epidemiological studies may be of value in determining whether a true association exists.

Adenoma↗

Acute pseudohepatitis in a chronic substance abuser secondary to occult seat belt injury.

Causes of a massive elevation in serum aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in the substance-abusing patient include viral hepatitis and drug hepatotoxicity. A patient chronically addicted to injection heroin and cocaine presented to the emergency room in a confused state and was admitted to a medical ward with an AST of 4120 U/L, ALT 3820 U/L and right upper quadrant discomfort. Investigations for viral and hepatotoxic causes for the liver dysfunction revealed only hepatitis C seropositivity. A computed tomogram of the abdomen, however, revealed a significant contusion to the right lobe of the liver consistent with traumatic injury. A motor vehicle accident, in which the patient was wearing a seat belt, and which had occurred a few days before admission and had been thought to be minor, was the cause of the liver dysfunction. Significant blunt abdominal traumatic injuries are usually managed exclusively by surgical trauma units. This case underlines the need for medical specialists to be aware of hepatic contusion injuries and to have a high index of suspicion when investigating unexplained hepatocellular dysfunction in chronic substance abusers who have been in motor vehicle accidents.

Accidents, Traffic↗

Donor-specific stimulation of peripheral blood mononuclear cells from recipients of orthotopic liver transplants is associated, in the absence of rejection, with type-2 cytokine production.

In this study, we examined the cytokine production by human peripheral blood mononuclear cells (PBM) from recipients of orthotopic liver transplants which had been stimulated by donor-specific alloantigen. Levels of interleukin (IL)-2, IL-4, interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta produced in vitro from PBM of 15 transplant recipients at 5-7 months post transplantation were analysed after donor-specific, third-party, or non-specific stimulation. Mononuclear cell proliferation in response to stimulation and cytokine mRNA from the cell cultures were assayed. Donor-specific antigen was obtained from donor spleen cells which had been obtained and frozen in liquid nitrogen at the time of organ retrieval. Third-party restimulation used equivalent numbers of spleen cells pooled from the other 14 organ donors. Cytokine production was correlated with the clinical condition of the patient, including biopsy results when available, and biochemical data. The data show a highly significant correlation between the donor-specific- and third-party- stimulated IL-4 and IL-10 production from recipient PBM with stable liver graft function as assessed by histopathology and/or biochemistry. This correlation was independent of level of immunosuppression. These data strongly support a role for IL-4 and/or IL-10 in the induction and/or maintenance of tolerance to human liver allografts. Measurement of the levels of these cytokines from recipient PBM after donor-specific antigen stimulation in vitro may be a useful test for monitoring for acute allograft rejection.

Adjuvants, Immunologic↗