Multiple sclerosis: genetic versus environmental aetiology: epidemiology in Israel updated

The incidence and prevalence of multiple sclerosis (MS) were compared, controlling for age, in native-born Israelis of different origins and in immigrants to Israel. This comparison was carried out in two populations, countrywide and in Jerusalem. In the countrywide population, ascertainment was based mainly on hospitalizations; it included 252 patients who were native-born and 150 who had immigrated from Africa-Asia (AA immigrants). The 89 MS patients of Jerusalem also included patients diagnosed in outpatient clinics. In native-born Israelis whose father was born in Europe-America (I-EA), the incidence and prevalence of MS were found to be as high as or even higher than that found previously in immigrants from Europe-America. Among native-born Israelis whose father was born in Africa or Asia (I-AA), the yearly age-adjusted incidence and prevalence rates were found to be 1.4- to 1.8-fold higher than among AA immigrants, pointing to environmental factors. The incidence and prevalence rates in the I-EA were 1.2- to 1.6-fold higher than in the I-AA, pointing to genetic factors. These results seem to point to both environmental and genetic factors in the aetiology of MS. Further research is needed, however, to disentangle the genetic factors from possible environmental differences in the two ethnic groups.     

Association of donor TNFRSF6 (FAS) gene polymorphism with acute rejection in renal transplant patients: a case-control study.

BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes.     

Does Preoperative Coronary Angioplasty Improve Perioperative Cardiac Outcome?

Background: Percutaneous coronary intervention (PCI) is performed in patients with coronary artery disease who are undergoing major noncardiac procedures to reduce perioperative cardiac morbidity and mortality. However, the impact of this approach on postoperative outcome remains controversial.

Methods: The authors analyzed a cohort of 1,152 patients after abdominal aortic surgery in which 78 patients underwent PCI. A propensity score analysis was performed. Also, using a logistic regression model, the authors determined variables associated with a severe postoperative coronary event or a death in patients without PCI. Then, in patients with PCI, they compared the expected and observed outcome.

Results: Five variables (age > 75 yr, blood transfusion > 3 units, repeated surgery, preoperative hemodialysis, and previous cardiac failure) independently predicted (with 94% correctly classified) a severe postoperative coronary event, and five variables (age > 75 yr, repeated surgery, previously abnormal ST segment/T waves, previous hypertension, and previous cardiac failure) independently predicted (with 97% correctly classified) postoperative death. In the PCI group, the observed percentages of patients with a severe postoperative coronary event (9.0% [95% confidence interval, 4.4-17.4]) or death (5.1% [95% confidence interval, 2.0-12.5]) were not significantly different from the expected percentages (8.2 and 6.9%, respectively). When all patients were pooled together, the odds ratios of PCI were not significant. The propensity score analysis provided a similar conclusion.     

Selective alterations in the patterns of newly synthesized proteins by acetaminophen and its dimethylated analogues in primary cultures of mouse hepatocytes.

Alterations in protein synthesis following exposure to and recovery from hepatotoxic doses of acetaminophen (APAP) and its analogues, 3,5-dimethyl acetaminophen (3,5-DMA) and 2,6-dimethyl acetaminophen (2,6-DMA), were investigated in primary cultures of mouse hepatocytes. The rates of protein synthesis decreased within 4 hr after administration of 10 mM APAP and occurred after significant depletion of intracellular glutathione and covalent binding of APAP to proteins, but preceded the leakage of lactate dehydrogenase into the media. The inhibition of protein synthesis was reversible only if APAP exposure did not exceed 8 hr. Electrophoretic analysis of 35S-labeled proteins by one-dimensional SDS-PAGE revealed two consistent alterations in the patterns of newly synthesized proteins. First was a progressive diminution in the de novo synthesis of a protein migrating at approximately 58 kDa (p58). This was observed with APAP (10 mM) and 3,5-DMA (5 mM) but not with 2,6-DMA (10 mM). If exposure to APAP exceeded 8 hr, the biosynthesis of this protein was not only further decreased but was also no longer detectable during the recovery period. The second major alteration was an increase in the relative rate of biosynthesis of a 32-kDa protein (p32) following exposure and recovery from APAP and 3,5-DMA but not 2,6-DMA. Exposure to heme or arsenite induced the synthesis of a protein of similar molecular weight but did not result in the inhibition of p58 biosynthesis. The fact that the reactive metabolites of both APAP and 3,5-DMA, but not 2,6-DMA, possess oxidative properties suggests that the alterations in the synthesis of p32 and p58 may be related to an oxidative component induced by these compounds.     

Hepatic pseudotumor in long-standing biliary atresia patients undergoing liver transplantation.

A pseudotumor, giant regenerative nodule, or macroregenerative nodule is an unusual benign hepatic lesion in biliary atresia (BA) patients. This tumor may mimic malignant transformation and may preclude liver transplantation (LT). The clinical and imaging surveillance of patients after the Kasai procedure is therefore an important aspect of management of BA patients. Our objective is to report our experience and describe the incidence, imaging, and pathologic features of pseudotumors in BA patients awaiting LT. From August 1990 to December 2006, 133 LTs for BA were performed. Five (3.8%; 4 female, 1 male) patients were diagnosed with pseudotumor. The patients' records were reviewed. The diagnostic imaging modalities used were abdominal ultrasound (US), computed tomography (CT) scan, and magnetic resonance imaging (MRI). Histologic confirmation of the lesions was obtained in all cases. All underwent the Kasai operation in early infancy. Six of 7 lesions in 4 of 5 patients were demonstrated by pretransplant imaging. Two of 7 tumors were detected by US. Five of 7 lesions were detected by CT, and 5 of 7 lesions were demonstrated by MRI. In 1 patient, the lesion was not seen in the US, CT, or MRI but was found during surgery and confirmed by histology. An additional tumor was found incidentally during histologic examination in a patient previously diagnosed to have 2 tumors by CT and MRI. In another patient diagnosed to have 2 tumors on imaging, pathology revealed only a single tumor. In conclusion, although unusual, pseudotumor should be included in the differential diagnosis of liver masses in BA children.     

Intraoperative blood loss is a risk factor for complications in donors after living donor hepatectomy.

Complications in a donor are a distressing but inevitable occurrence, since graft procurement is a major undertaking. Although the technique for procurement has some similarities to hepatic resection, a donor is very unlike a patient with malignancy. The risk factors identified in these patients cannot be extrapolated to donors. Donor hepatectomy carried out from June 1995 to March 2005 in Chang Gung Memorial Hospital, Kaohsiung Medical Center was reviewed with the aim of identifying risk factors for complications. There were 204 living donor liver transplants, with 205 donor hepatectomies, as 1 living donor liver transplantation was a dual graft. Ten donors (4.88%) suffered complications. There was no difference in terms of age, gender, body weight, operation, and parenchymal time between those who had complications and those who did not. There was also no difference in liver function tests between the 2 groups of donors, but the total bilirubin was significantly higher in donors with complications. The graft weight and remnant liver volume were also similar. The proportion of donors with fatty liver was the same between the 2 groups. The mean blood loss in donors with complications was 170 +/- 79 mL, and that for donors without complications was 95 +/- 77 mL. There was a statistically significant greater blood loss in donors with complications (P < 0.05). The number of segments removed in donors with complications was also higher compared to donors without complications (P < 0.03). Using multivariate analysis, intraoperative blood loss and the number of segments removed were found to be independent risk factors for donor complications. Intraoperative blood loss during graft procurement must be kept low to minimize complications in donors.