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Biomedical subjects

S Mies

Publications and source records attributed to S Mies.

At least 19 recordsLinked to original sources

Long-term outcomes in liver transplant patients with hepatic C infection receiving tacrolimus or cyclosporine.

Choice of calcineurin inhibitor may be a contributing factor to deteriorating patient and graft survival following liver transplantation for hepatitis C virus (HCV). In our multicenter, open-label LIS2T study, de novo liver transplant patients stratified by HCV status were randomized to cyclosporine or tacrolimus. Follow-up data were obtained in an observational study of 95 patients. Mean follow-up was 34 and 37 months, respectively, for cyclosporine-treated (n = 47) and tacrolimus-treated (n = 48) patients. In patients not receiving antiviral therapy, 22 of 31 given cyclosporine (72%) and 24 of 29 given tacrolimus (83%) had biochemical recurrence of HCV. In 68 patients with at least one biopsy, histological evidence of HCV-related hepatitis was present in 27 of 31 (87%) cyclosporine-treated patients and 37 of 37 (100%) tacrolimus-treated patients (P = .02, chi-square test). Three-year actuarial risk of fibrosis stage 2 was 66% with cyclosporine and 90% with tacrolimus; for fibrosis stage 3 or 4 it was 46% and 80%, respectively. Three graft losses were attributed to HCV recurrence in cyclosporine-treated patients and six in tacrolimus-treated patients. Tacrolimus may be associated with increased risk of histological HCV disease recurrence compared to cyclosporine.

Adult↗

Phenotypic expression of familial amyloid polyneuropathy in Brazil.

Familial amyloid polyneuropathy (FAP) is an inherited amyloidosis mainly associated with transthyretin Val30Met variant. Clinical heterogeneity has been reported in different populations with FAP and Va130Met variant. In order to characterize FAP expression in Brazilians and to compare its features to those reported in other cohorts, 44 Brazilian patients (27 females, median age 36 [23-53] years) with FAP and the Val30Met variant were investigated. Approximately 40% of their family members, with the exception, of parents and siblings, had FAP. Most of the patients had symptoms of peripheral neuropathy at onset. Median age at onset was 32 [20-44] years. Earlier onset was observed in males (27 [20-43] years in males vs. 33 [20-44] years in females, P = 0.02) and in patients whose parents had FAP (31 [20-44] years vs. 40 [37-43] years in patients, respectively with and without affected parents, P = 0.03). Phenotypic expression of FAP in Brazil is similar to the one reported in Portugal, characterized by high disease penetrance, early onset, particularly in males and in subjects with affected parents, and major symptoms of peripheral neuropathy. These data highlight the influence of common genetic factors, shared by both groups of patients, in disease expression.

Adult↗

Subcapsular hematoma of the graft after liver transplantation.

Subcapsular hematoma of the graft is an underreported complication of liver transplantation (LT). Among 408 LT performed from September 1, 1985, to September 1, 2000, eight patients developed a subcapsular hematoma within 30 days after LT (8/408 = 2.0%). Among the six early cases observed, five required further surgical approaches due to hematoma progression, rupture, and hemorrhage. One patient underwent liver retransplantation due to uncontrollable hepatic hemorrhage. The two more recent cases were successfully treated by early opening of the Glisson's capsule with hemostasis of the hepatic raw bleeding surface. The five patients who developed acute renal failure required dialysis. Three patients died during hospitalization. Among the survivors, two were discharged on the postoperative (PO) day 15; the others on PO day 37, 38, and 56. In conclusion, subcapsular hematoma of the graft is a potentially serious complication of LT that may produce severe hemorrhage, shock, and in extreme cases, graft loss or even death. The severity of the complication is related to the extension of the decapsulated area of the graft. An early surgical approach with intentional opening of the hematoma before progression of the lesion seems to facilitate hemostasis and improve results.

Adult↗

Improved clinical outcomes for liver transplant recipients using cyclosporine monitoring based on 2-hr post-dose levels (C2).

BACKGROUND: A prospective, open-label, study was conducted at 29 centers in 9 countries, involving 307 de novo liver transplant patients to compare the clinical usefulness of monitoring 2-hr post-dose cyclosporine (CsA) levels (C2) with conventional trough cyclosporine blood levels (pre-dose) (C0). METHODS: Neoral oral therapy was initiated at 15 mg/kg/day and dose adjusted according to predetermined C2 or C0 target level ranges. The primary efficacy variable was treatment failure at 3 months, where evaluation was based on a composite endpoint of biopsy-proven rejection, treatment for rejection, graft loss, death, or premature withdrawal/discontinuation from the study. RESULTS: Baseline characteristics were similar between groups. Graft loss at 12 weeks (retransplantation or death) occurred in 6.8% C2 and in 7.0% C0 patients. Overall incidence of treated acute rejection was lower for C2 (23.6%) than C0 patients (31.6%) (P=0.144, Cochran-Mantel-Haenszel [CMH] test). In hepatitis C virus (HCV)-negative patients, the incidence of rejection in the C2 group was significantly less than in the C0 group (21.2% vs. 33.0%; P<0.05), whereas in HCV-positive patients, the rejection rate was similar in both groups (26.7% for C2 group vs. 27.3% for C0 group: P=0.81). C2 patients (n=16) who reached minimum target CsA levels by day 3 had a notably low incidence of rejection (12.5%), whereas there was no difference in the incidence of rejection in C0 patients, irrespective of time to reach target level. For biopsy-proven acute rejections (21.6% for C2 vs. 30.4% for C0), the incidence of moderate and severe histological diagnosis was significantly lower in the C2 group than in the C0 group (47% vs. 73%; P=0.01). Safety profiles were similar between the two groups, with few patient withdrawals due to adverse events (9.5% for C2; 7.0% for C0). CONCLUSIONS: Using C2 monitoring, the overall incidence of acute cellular rejection was lower compared with the C0 group, and the histological severity of acute rejections was shown to be significantly milder for the C2 group, indicative of good long-term prognosis. These data demonstrate that the use of C2 monitoring is superior to C0 and results in a reduction in the incidence and severity of acute cellular rejection without detrimental effect on the drug safety profile.

Administration, Oral↗

Familial amyloidotic polyneuropathy type 1 in Brazil is associated with the transthyretin Val30Met variant.

UNLABELLED: Familial amyloidotic polyneuropathy type 1 (FAP1) is an inherited systemic amyloidosis that is secondary to the deposition of transthyretin (TTR) variants in peripheral nerves and in certain visceral organs. More than 50 distinct mutations have already been described in the TTR gene. Yet, the most common mutation found worldwide is a substitution of valine for methionine in position 30 (Val30Met). Currently, the variants of TTR in Brazilian FAP1 patients remain largely unknown and the aim of this study was to analyze the frequency of the TTR Val30Met mutation in such Brazilian subjects. METHODS: Thirty-two FAP1 patients belonging to 24 different families were studied for the presence of Val30Met variant by PCR-RFLP. RESULTS: All Brazilian FAP1 subjects studied were positive for the TTR Val30Met variant. As expected, all of them were heterozygous for the mutation. CONCLUSION: TTR Val30Met mutation was the sole TTR variant found in Brazilian FAP1 patients in this cohort, and it was present even in those subjects without a clear history of Portuguese ancestry.

Adult↗

Systemic and hepatic hemodynamics in hepatosplenic Manson's schistosomiasis with and without propranolol.

Systemic and hepatic hemodynamics were prospectively studied in 11 patients with Manson's schistosomiasis and portal hypertension, as well as alterations resulting from the use of propranolol. It was decided that patients whose portal pressure was reduced by 30% with the use of the drug would not undergo surgery and that treatment would consist of the chronic use of propranolol, associated with sclerosis of esophageal varices. This objective was not met by any of the patients whose portal pressure was measured and the study was interrupted. Results show that patients with Manson's schistosomiasis and portal hypertension have hyperdynamic circulation, mild pulmonary hypertension, greatly increased splenic blood flow, and preservation of total hepatic blood flow. Administration of propranolol corrects hyperdynamic circulation, aggravates pulmonary hypertension, does not alter portal pressure and reduces the sectorial portal blood flows, especially of the azygos vein, with maintenance of total hepatic blood flow. These data favor the hypothesis of portal overflow in the physiopathology of portal hypertension of schistosomiasis.

Adrenergic beta-Antagonists↗

Apolipoprotein and lipid abnormalities in chronic liver failure.

Total serum lipids, as well as apolipoproteins A-I (apo A-I) and B (apo B), were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P < 0.001). Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P < 0.001). However, the reduction of HDL cholesterol (HDLc) was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P < 0.05). We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver.

Apolipoprotein A-I↗

Hepatitis C virus infection in Schistosomiasis mansoni in Brazil.

The involvement of the hepatitis C virus (HCV) in the severity of liver disease in chronic schistosomiasis was investigated in 215 Brazilian patients with S. mansoni infections, but without evidence of hepatitis B surface antigen (HBsAg). Forty-three had hepatointestinal (HIS) and 172 had hepatosplenic schistosomiasis (HSS), and 135 had compensated (HSSC), and 37 had decompensated (HSSD) liver disease. Fifty-two (24%) were found to have evidence of HCV infection (seropositive for anti-HCV antibodies and/or HCV-RNA). These comprised 35 (95%) of the 37 with HSSD, 16 (12%) of the 135 with HSSC, and 1 (2.4%) of the 43 with HIS, compared with only 1 (2%) of 50 control patients without S. mansoni. Testing of matched liver tissue and peripheral blood mononuclear cells (PBMCs) from 25 patients (6 HSSC and 19 HSSD) with HCV infections showed that 17 (68%) had "active" viral infections, in that negative strand HCV-RNA (the presumed replicative intermediate of the virus) could be detected in liver and/or PBMCs. Among these 25, negative strand HCV-RNA was found in 16 (84%) of the 19 with chronic active hepatitis, but in only 1 (17%) of the 6 with mild or inactive disease (P < 0.01). HCV-RNA was detected in matched spleen specimens from 9 of 10 patients (all of whom were also positive in PBMCs), suggesting that the spleen is an important extrahepatic reservoir of the virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hepatitis B virus infection in schistosomiasis mansoni.

Schistosomiasis and hepatitis B virus (HBV) infection are very common in Brazil but the interrelationships between the two infections are poorly understood. We have undertaken a detailed serological study of the prevalence of HBV markers in 189 Brazilian patients with chronic schistosomiasis mansoni, 46 with hepatointestinal (HIS) and 143 with hepatosplenic (HSS) schistosomiasis, 12 of the latter having decompensated liver disease (HSSD), and in 50 control patients. Sera were tested for HBsAg, anti-e, anti-HBc, anti-HBs and HBV-DNA. Eighty-three (44%) of the 189 schistosoma patients had at least one marker of HBV infection, 18 of whom (10%) were seropositive for HBsAg. All the controls were HBsAg negative, but ten (20%) had anti-HBc and anti-HBs. There was no significant difference in the frequency of these markers between HIS (14/46, 30.4%), HSSC (43/131, 34.5%), and the controls. Among the HBsAg-positive patients, one had HIS (HBV-DNA negative), seven had HSSC (one HBV-DNA positive) and ten had HSSD (six HBV-DNA positive), a significant association of HBV carriage with HSSD (P << 0.001). Mean (+/- SD) ALT values were significantly (P < 0.001) higher in HBsAg-positive HSSD patients (70.7 +/- 18 IU/liter) than in those with HSSC (29.5 +/- 15 IU/liter). Liver biopsies were performed in 12 HBsAg-positive patients (one with HIS, three with HSSC, and eight with HSSD) and in 50 HBsAg-negative HSSC patients. Seven of the eight HSSD patients had chronic active hepatitis with cirrhosis, and one had inactive cirrhosis. All three patients with HSSC and the one with HIS had chronic persistent hepatitis, with periportal fibrosis in three.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗