Homocysteine levels and sustained virological response to pegylated-interferon alpha2b plus ribavirin therapy for chronic hepatitis C: a prospective study.

BACKGROUND: Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) alpha plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate. AIMS: To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment. METHODS: Patients were treated with pegylated interferon alpha-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B(12), folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination. RESULTS: Homocysteine levels were deranged (>16 micromol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 micromol/L in SVR patients and 15.5 micromol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390-44.837, P=0.0001), homocysteine <16 micromol/L (odds ratio: 3.397, 95% confidence interval: 1.033-11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125-9.458, P=0.029) were independent predictors of SVR. CONCLUSIONS: In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFNalpha plus ribavirin treatment, while polymorphisms of MTHFR are not.

Prophylaxis of thromboembolism in bariatric surgery with parnaparin.

BACKGROUND: There are limited data on appropriate dosing of low-molecular-weight heparins (LMWHs) for venous thromboembolism (VTE) prophylaxis in bariatric surgery. The primary objective of this preliminary study was to evaluate the preoperative effects of increasing doses of the LMWH parnaparin on coagulation in severely obese patients undergoing bariatric surgery. METHODS: Severely obese patients (BMI > 50 kg/m(2)) were administered three increasing single doses of parnaparin (3200, 4250, and 6400 IU) on the three consecutive days leading up to biliointestinal bypass surgery. Activated partial thromboplastin time (APTT), anti-factor IIa and anti-factor Xa levels were measured 1 h before and 4 h after dosing. The highest dose (6400 IU/day) was continued from the day of surgery until day 30 (recovery period). Intermittent pneumatic compression and stockings were applied during surgery and the recovery period, respectively. Lower limb echoDoppler and phleboscintigraphy, and pulmonary scintigraphy were used for VTE detection. RESULTS: Ten patients (mean BMI 52.4 kg/m(2)) were recruited into this study. During the preoperative dosing phase, parnaparin dose-dependently prolonged APTT, with the 6400 IU dose significantly prolonging APTT versus the lower doses. Meanwhile, anti-factor Xa and anti-factor IIa activity was increased by the 4250 and 6400 IU doses. After surgery, one patient with heparin resistance experienced pulmonary embolization. No bleeding complications were observed. CONCLUSION: The dose-response data reported in this preliminary study suggest that parnaparin doses of 4250 and 6400 IU may provide effective prophylaxis for VTE in patients undergoing bariatric surgery. However, given the small number of patients, larger, well-controlled trials are required to confirm these findings.

NT-proBNP, IGF-I and survival in patients with chronic heart failure.

OBJECTIVE: Growth hormone (GH) resistance with a reduction of insulin-like growth factor-I (IGF-I) serum concentrations seems to be implicated in the catabolic process associated with chronic heart failure (CHF). However, data concerning the prognostic value of these alterations in CHF patients without cachexia are scant. In this study, we aimed to determine in CHF patients the prognostic value of IGF-I/GH ratio and its relationships with N-terminal brain natriuretic peptide (NT-proBNP), a known marker of prognosis in these patients. DESIGN: We enrolled 82 non-cachectic patients, mean age 61+/-13 years, with ejection fraction <40% and predischarge New York Heart Association (NYHA) functional classes II-IV. All patients underwent clinical examination, two-dimensional echocardiography and NT-proBNP, GH and IGF-I measurement with log IGF-I/GH ratio calculation. Mortality and clinical status was documented at follow-up (18.4+/-8.1 months). RESULTS: During follow-up 17 patients died of cardiac causes. Non-survivors were at baseline in higher NYHA class (P<0.05) and showed higher values of NT-proBNP (P<0.001) than survivors; differently IGF-I, and log IGF-I/GH ratio were lower (P<0.05). At Cox multivariate analysis, NT-proBNP (P<0.001) and IGF-I/GH ratio (P<0.05) were independent predictors of death. CONCLUSIONS: High NT-proBNP levels and low IGH-I/GH ratio may be useful to stratify CHF patients at higher risk of cardiac death.

The contribution of omental adipose tissue to adipokine concentrations in patients with the metabolic syndrome.

PURPOSE: To examine differences in peripheral vascular endothelial growth factor (VEGF), interleukin-6 (IL6) and cortisol concentrations between patients with both visceral obesity and metabolic syndrome, and lean controls. In a subsample of metabolic patients underwent abdominal surgery, the adipokine concentrations were measured in venous blood from the omentum to determine information on some processes of synthesis. METHODS: Forty-two healthy lean controls and 46 overweight-obese patients with central adiposity and stigmata of metabolic syndrome were studied. In a subsample of 11 metabolic patients undergoing non-bariatric surgery, blood samples from omental and peripheral veins were taken intraoperatively to determine VEGF, IL6 and cortisol concentrations. RESULTS: Median levels (range) of peripheral VEGF and IL6 were higher in patients than in controls [31.5 (3-112) pg/mL vs 21.35 (9-41.9) pg/mL (P < 0.05) and 5.50 (1.40-13) pg/mL vs 1.15 (0.3-1) pg/mL (P < 0.0001)]. On the other hand, concentrations of VEGF and IL6 from the omental and peripheral veins were similar in the surgery sub-group. Peripheral cortisol concentrations were not higher in patients than in controls, nor were omental concentrations different from the peripheral. Omental and peripheral VEGF and cortisol values were correlated, whereas no association was found between omental and peripheral IL6. CONCLUSIONS: In the presence of abdominal obesity, VEGF and IL6 concentrations are increased in the systemic circulation. The contribution of visceral adipose tissue to circulating levels of VEGF and IL6 was modest.

Inverse association between carotid intima-media thickness and the antioxidant lycopene in atherosclerosis.

BACKGROUND: Antioxidants may prevent atherosclerosis by interfering with endothelial activation, which involves the expression of endothelial adhesion molecules. The aim of this study was to explore the relationship between plasma levels of some lipid-soluble antioxidants (gamma-tocopherol, alpha-tocopherol, lycopene, beta-carotene, and ubiquinone), carotid maximum intima-media thickness (IMTmax), an index of atherosclerotic extension/severity, and soluble adhesion molecules (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], and E-selectin), which are taken as a reflection of vascular cell expression of adhesion molecules. METHODS: We studied 11 healthy control subjects, 11 patients with uncomplicated hypertension (UH), and 11 patients with essential hypertension plus peripheral vascular disease (PVD) who were matched for age, sex, smoking habit, and body mass index. RESULTS: Patients with PVD had elevated IMTmax (2.7 [1.1-3.1] mm, median [range]) compared with both patients with UH(1.2 [0.8-2.4] mm) and control subjects (1.0 [0.6-2] mm). In patients with PVD, soluble (s)VCAM-1 and sICAM-1 were also significantly higher than in the 2 other categories. Plasma levels of lycopene had a trend toward lower values in patients with PVD compared with other groups (P =.13). A statistically significant correlation was found between lycopene and IMTmax (r = 0.42, P =.014) at univariate analysis, which persisted at multivariate analysis (P <.05) and was independent of low-density lipoprotein cholesterol, creatinine clearance, and plasma insulin. Plasma lycopene did not significantly correlate with any of the soluble adhesion molecules tested. CONCLUSIONS: We conclude that the inverse relationship of plasma lycopene with IMTmax is compatible with a protective role of this natural dietary antioxidant in atherosclerosis, although the mechanism of protection does not apparently involve a decrease in endothelial activation measured through soluble adhesion molecules.

The soluble transferrin receptor (sTfR)-ferritin index is a potential predictor of celiac disease in children with refractory iron deficiency anemia.

The soluble transferrin receptor (sTfR) distinguishes iron deficiency anemia from other types of anemia. Refractory iron deficiency anemia is often the onset symptom in malabsorption-induced celiac disease. We evaluated whether sTfR levels distinguish celiac disease-associated iron deficiency anemia from iron deficiency anemia of other origin. To this aim we measured sTfR and ferritin levels and their ratio (the sTfR/ferritin index) and other hematological parameters in 42 anemic children (20 with and 22 without celiac disease) vs. 22 non-anemic children with celiac disease and 31 healthy controls (age range 4-12 years). Hemoglobin parameters, mean cell volume, and serum iron and ferritin levels were decreased to a similar extent in the anemic patients (celiac and non-celiac). The sTfR level in non-anemic celiac patients was similar to that of normal controls (1.7+/-0.35 mg/L), whereas it was significantly increased in non-celiac and celiac anemic patients (2.2+/-0.5 mg/L, p<0.05 and 2.7+/-1.2 mg/L, p<0.001, respectively). The sTfR/ferritin index was also increased more in the anemic celiac patients (mean 4.4, range 1.5-12.0) than in anemic non-celiac children (mean 2.6, range 1.4-4.0) compared with non-anemic children (mean 1.2, range 0.7-2.0). Differences were more pronounced when ferritin was <5 ng/mL. Thus, the sTfR/ferritin index may be a predictive measure in discriminating anemic patients with celiac disease from those without celiac disease.

Effect of paraformaldehyde on platelet size and on measurement of surface IgG.

In many platelet assays, as in measurement of platelet-adherent IgG (PAIgG), platelets are fixed in paraformaldehyde (PFA). To better clarify the effect of PFA on platelet size and on PAIgG measurement we compared PAIgG levels in a series of 40 samples, with or without PFA fixing. We used an ELISA which was set up on unfixed platelets and gave excellent results in terms of linearity (r = 0.923), precision (mean CV = 5%) and correlation with a platelet suspension immunofluorescence test. We found PAIgG values in unfixed platelets were about 10-fold higher than in PFA-fixed (0.411 +/- 0.172 fg/platelet vs. 0.035 +/- 0.019 fg/platelet). This discrepancy could be a consequence of the smaller mean platelet volume (MPV) of washed platelets when fixed in PFA (8.0 +/- 0.8 fl as compared to 10.1 +/- 1.07). This effect of PFA could decrease the amount of binding sites for IgG exposed on the platelet membrane and hence explain the significantly lower PAIgG values observed in fixed platelets. The PAIgG measurements on unfixed platelets from 200 healthy subjects displayed a Gaussian distribution with a mean +/- SD of 0.32 +/- 0.13 fg/platelet, i.e., 1200 +/- 500 molecules/platelet.