Duplex ultrasound and renin ratio predict treatment failure after revascularization for renal artery stenosis.

BACKGROUND: The aim of this study was to find predictors to identify patients with hypertension who will not improve after removal of renal artery stenosis (RAS). METHODS: Prospective study of patients with unilateral stenosis (>60% diameter reduction) and hypertension in 24-h measurements despite antihypertensive drugs, who underwent revascularization (surgery/angioplasty). Examinations were performed before treatment and after 3 and 6 months after exclusion of restenosis. Studies included 24-h blood pressure, creatinine clearance, 99Tc MAG3 scintigraphy, and measurements of renal vein plasma renin activity (PRA). Intrarenal resistance indices (RI) were determined with duplex ultrasound before and 30 min after administration of intravenous enalaprilat. Improvement of hypertension was defined by a score consisting of 24-h mean arterial pressure and the number of antihypertensive drugs. RESULTS: From December 2000 to December 2003, 50 patients completed the study. Improvement of hypertension was observed in 18 patients (36%). Comparison between responders (n = 18) and nonresponders (n = 32) revealed significant differences only for RI and PRA measurements. The largest area under the curve in receiver-operating characteristic (ROC) analysis for prediction of no improvement of hypertension was found for RI (stenosis side), which was nearly identical for measurements before and after administration of angiotensin-converting enzyme (ACE) inhibitor. The highest sensitivities and specificities predicting which patients will not improve were found for RIs > or = 0.55. The highest univariate odds ratio (OR 44, confidence interval [CI] 4.8-404) was found for the parameters of RI > or = 0.55 and a renin ratio of <1:1.5. CONCLUSIONS: Resistance indices of the poststenotic kidney above 0.55 and a negative renin ratio can predict a poor outcome concerning arterial blood pressure response after restoration of renal blood flow for unilateral renal artery stenosis.

Real-time imaging with the sonographic contrast agent SonoVue: differentiation between benign and malignant hepatic lesions.

OBJECTIVE: We investigated the ability of contrast-enhanced sonography with SonoVue (Altana Pharma, Konstanz, Germany), a sulfur hexafluoride microbubble contrast agent, to reveal differences between benign and malignant focal hepatic lesions. METHODS: One hundred twenty-six lesions in 124 patients with focal hepatic lesions detected by B-mode sonography (hepatocellular carcinoma, n = 36; metastasis, n = 25; cholangiocellular carcinoma, n = 1; lymphoma, n = 2; focal nodular hyperplasia, n = 9; adenoma, n = 4; regenerative cirrhotic nodule, n = 13; hemangioma, n = 29; and focal hyposteatosis, n = 7) were examined in a prospective study. After intravenous injection of 2.4 mL of SonoVue, the liver was examined continuously for 3 minutes by low-mechanical index pulse inversion sonography. RESULTS: For the discrimination of malignant versus benign liver lesions, SonoVue-enhanced sonography improved sensitivity from 78% to 100% and specificity from 23% to 92% compared with baseline sonography. Receiver operating characteristic analysis revealed a significant improvement in this discrimination (area under the receiver operating characteristic curve, 0.510 +/- 0.054 [SD] at baseline sonography, 0.998 +/- 0.003 with SonoVue-enhanced sonography; P < .001). The following flow patterns in the early phase were diagnosis specific: early central starlike pattern for focal nodular hyperplasia, peripheral globular-nodular pattern for hemangioma, and diffuse arterial enhancement for malignant lesions. Homogeneous enhancement in the late phase was predictive for benign lesions (P < .001). Conversely, 93% of patients without contrast enhancement in the late phase had malignant lesions (P < .001). CONCLUSIONS: SonoVue-enhanced sonography has greater specificity and sensitivity than baseline sonography for the differentiation of benign and malignant liver lesions.

Locoregional opening of the rodent blood-brain barrier for paclitaxel using Nd:YAG laser-induced thermo therapy: a new concept of adjuvant glioma therapy?

BACKGROUND AND OBJECTIVES: Nd:YAG laser-induced thermo therapy (LITT) of rat brains is associated with blood-brain barrier (BBB) permeability changes. We address the question of whether LITT-induced locoregional disruption of the BBB could possibly allow a locoregional passage of chemotherapeutic agents into brain tissue to treat malignant glioma. STUDY DESIGN/MATERIALS AND METHODS: CD Fischer rats were subject to LITT of the left forebrain. Disruption of the BBB was analyzed using Evans blue and immunohistochemistry (IH). Animals were perfused with paclitaxel, and high-pressure liquid chromatography (HPLC) was employed to analyze the content of paclitaxel in brain and plasma samples. RESULTS: LITT induces an opening of the BBB as demonstrated by locoregional extravasation of Evans blue, C3C, fibrinogen, and IgM. HPLC proved the passage of paclitaxel across the disrupted BBB. CONCLUSIONS: LITT induces a locoregional passage of chemotherapeutic agents into the brain tissue. This is of potential interest for the treatment of brain tumors.

HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis.

BACKGROUND/AIMS: The impact of heterozygous HFE mutations on the course of chronic hepatitis C and iron indices was studied. METHODS: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients. RESULTS: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). HFE heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and fibrosis scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to HFE wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to HFE wildtypes. Considering all HFE heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for cirrhosis and 3.1 (CI 1.3-7.3; P<0.009) for fibrosis were calculated. CONCLUSIONS: C282Y or H63D heterozygosity is an independent risk factor for liver fibrosis and cirrhosis in HCV infected individuals. Screening for HFE mutations should be considered in HCV infection.

Differentiating hyperlipidaemia associated with antiretroviral therapy.

BACKGROUND: Hyperlipidaemia associated with antiretroviral treatment has led to concerns for an increased cardiovascular risk in HIV-infected patients. OBJECTIVE: To assess this cardiovascular risk by comparing the lipoprotein pattern of antiretroviral-treated and untreated HIV-positive patients with patients with familial combined hyperlipidaemia (high cardiovascular risk) or familial hypertriglyceridaemia (low cardiovascular risk). METHODS: Fasting serum samples were drawn from consecutive patients with HIV infection or lipoprotein disorders. Total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1 and B were determined in serum. Very low density lipoprotein (VLDL) was prepared by ultracentrifugation and analysed for cholesterol, triglycerides and apolipoprotein B. RESULTS: Lipoprotein disorders were found in 114/187 HIV-positive patients (61%). Of these, according to the Fredrickson classification, 10% were type IIa (elevated LDL-cholesterol), 14% type IIb (elevated LDL- and VLDL-cholesterol) and 76% were type IV (elevated VLDL-cholesterol). VLDL composition was analysed in 34 HIV-positive patients with type IV hyperlipidaemia. The ratio of VLDL-triglycerides to VLDL-apolipoprotein B in these patients was 16.2 +/- 6.0. This ratio was not different from 14 patients with famlial hypertriglyceridaemia (16.9 +/- 6.0; = 0.61), but differed substantially from 10 patients with familial combined hyperlipidaemia (6.8 +/- 1.0; < 0.0001). CONCLUSIONS: In HIV-infected patients with high VLDL, large VLDL particles were found with no increase in number. This pattern resembles familial hypertriglyceridaemia. It is different from familial combined hyperlipidaemia, where an increase in number of small-sized VLDL particles occurs. Further research is needed to assess the contribution of VLDL-associated hypercholesterolaemia in those taking antiretroviral drugs to the cardiovascular risk profile of HIV-positive patients.

Transforming growth factor beta type II receptor expression in gastric cancer: evidence for two independent subgroups.

Transforming growth factor beta type II receptor (TGFbeta-IIR) has been found to be altered in primary gastrointestinal carcinomas. So far relatively few facts are known about the expression of TGFbeta-IIR in primary gastric cancer. Therefore, in the present study, TGFbeta-IIR expression was analyzed in 130 primary gastric carcinomas and correlated with clinicopathological findings, the presence of a mutator phenotype, the mutational status of the TGFbeta-IIR polyadenine tract and survival. TGFbeta-IIR expression was analyzed immunohistochemically. Microsatellite instability was evaluated using a PCR-based assay and the polyadenine run inside the TGFbeta-IIR gene was sequenced. A complete loss of TGFbeta-IIR expression could be found in 55 (42.3%) of these carcinomas. Loss of TGFbeta-IIR expression was significantly correlated with diffuse-type carcinomas according to the Lauren classification as well as with signet ring cell carcinomas and a lower grade of differentiation. No correlation was found with the overall prognosis, the presence of a mutator phenotype, or a mutated TGFbeta-IIR. Thus, our data suggest the existence of a further definite subgroup of diffuse-type gastric carcinomas with altered TGFbeta-IIR expression, independent from a mutator phenotype with TGFbeta-IIR gene mutations. However, according to our results, in gastric cancer neither loss of TGFbeta-IIR expression nor mutations of the TGFbeta-IIR are of prognostic value.

Kidney transplantation in the elderly: age-matching as compared to HLA-matching: a single center experience.

BACKGROUND: We report the short-term outcome of our patients participating within the Eurotransplant age-matching program, where kidneys from donors >65 years are transplanted to recipients >65 years regardless of human leukocyte antigen (HLA) compatibility but with short cold ischemia times, in comparison with patients >60 years transplanted with HLA-matching. METHODS: Twenty-five patients (66.7+/-2.6 years) (donors 69+/-4.3 years) participated in this program (group A). The control group consisted of 21 patients (63+/-2.6 years) (group B) (donors 47.6+/-17.3 years). RESULTS: Despite significant differences in donor age, cold ischemia time (12.3+/-4.6 hr in A, 22.8+/-4.8 hr in B, P<0.001) and a mean of 4.4+/-1.4 vs. 2.3+/-1.6 HLA-mismatches (P<0.001), there was no difference regarding the incidence of delayed graft function (64 vs. 57%), rejections (52 vs. 66.7%), infections (56 vs. 52.4%), and other complications (80 vs. 71.4%). Mean serum creatinine after 6 months was 1.94+/-0.49 and 1.83+/-0.67 mg/dl (NS). CONCLUSION: The short-term results of the age-matching program are promising and comparable with results from patients of similar age with HLA-matching.