Plasma leptin and TNF-alpha levels in chronic hepatitis C patients and their relationship to hepatic fibrosis

The aim of this study was to examine the possible relationship between the plasma levels of leptin and tumor necrosis factor (TNF)- and the stage of hepatic fibrosis in a cohort of patients with chronic hepatitis C. Leptin and TNF levels were measured by RIA in 135 patients and in 75 age- and sex-matched controls. Liver disease was evaluated by the stage of fibrosis and the extent of inflammatory infiltrate in the liver biopsy. Leptin levels correlated with BMI values in healthy controls and in patients with chronic hepatitis C (men, r = 0.61, P = 0.0001; women, r = 0.68, P = 0.003). Leptin levels increased as hepatic fibrosis stage progressed both in male and in female patients (P < 0.001); also, TNF levels were higher in patients with an advanced stage of fibrosis (P = 0.006). In these patients, levels of leptin increased according to the progression of the stage of fibrosis; these data suggest that leptin may play a role in the regulation of hepatic fibrosis.     

A study of prognostic factors in blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia

In 80 patients with Ph-positive chronic myelogenous leukaemia the main clinical, haematological and cytogenetical data were recorded at diagnosis of blast crisis and evaluated for prognostic significance. At the time of the analysis 73 patients had died, with a median survival of 4-8 months from diagnosis of blast crisis for the whole series. When analysed as a time-dependent variable, the achievement of a favourable response to chemotherapy resulted in a longer patient's survival. On the other hand, the univariate analysis identified six pretreatment characteristics associated with a poorer prognosis: a longer chronic phase, presence of extramedullary blastic involvement, a platelet count below 200 x 10(9)/l, a less marked leucocytosis, a blood blast cell percentage higher than 10%, and presence of trisomy 8. The latter parameters were included in a multiple regression model together with the blast cell phenotype (lymphoid versus non-lymphoid), and only four of them (trisomy 8, duration of chronic phase, platelet count, and leucocyte count) retained their prognostic influence. When the therapeutical response was also included in the regression model, it proved to be the most important prognostic variable, followed by trisomy 8, length of chronic phase, extramedullary disease, and platelet count, whereas the leukocyte count lost its predictive value. Thus, in spite of the short overall survival of blast crisis patients, the identification of prognostic factors in such a haematological condition may be of interest, especially in the interpretation of new therapeutical approaches.     

Bronchial hyperreactivity in patients who inhale heroin mixed with cocaine vaporized on aluminum foil

BACKGROUND: In our area, inhaling heroin mixed with cocaine vaporized on aluminum foil, known as rebujo, is becoming more and more common. AIM: To define the prevalence and the characteristics of bronchial disease (wheezing, bronchial hyperreactivity [BHR], and asthma) present in subjects inhaling heroin mixed with cocaine vaporized on aluminum foil. MATERIALS AND METHODS: Ninety-one subjects who inhaled the drug mixture were included in the study: 62 subjects were from a drug rehabilitation center (INH-I group), and 29 subjects were among patients admitted to our hospital for a variety of reasons (INH-II group). A questionnaire was completed in both groups, as well as IgE determination and lung function tests (spirometry and methacholine challenge). The control group consisted of 122 individuals who did not inhale the drug mixture, and were chosen randomly from the general population (NO-INH group). All subjects were tobacco smokers. RESULTS: In the INH-I group, there was a 41.9% prevalence of wheezing over the past 12 months, a 44.4% prevalence of BHR, and a 22.02% prevalence of asthma, defined as wheezing plus BHR. In the NO-INH group, these values were 32.78% (p = 0.22), 15.57% (p < 0.0001), and 8.19% (p < 0.01), respectively. Of the subjects who inhaled the drug mixture and denied having symptoms prior to the use of the drug mixture, 31.4% had wheezing develop after commencing use of the drug, following a mean latency of 4.09 months. Wheezing remitted in only 7.6% after discontinuation of the drug. CONCLUSIONS: (1) There is a real increase in BHR in subjects who inhale heroin mixed with cocaine vaporized on aluminum foil; and (2) this BHR is associated with wheezing that develops after a variable period of latency, once drug inhalation begins, and persists despite discontinuation of the drug.     

A Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Efficacy and Safety of Oral Nalmefene HCI for Alcohol Dependence

A dozen studies have been published showing that opiate antagonists suppress alcohol drinking in animals, and two independent placebo-controlled, double-blind clinical trials of naltrexone found this agent was associated with decreased alcohol craving and consumption in alcohol-dependent patients. Nalmefene is a newer opiate antagonist that has a number of potential advantages over naltrex-one in the treatment of alcoholism, including no dose-dependent association with liver toxicity and more effective binding to central opiate receptors. Consequently, a double-blind pilot study was conducted to gather preliminary data on the safety and efficacy of nalmefene for reducing alcohol consumption in alcohol-dependent subjects. Twenty-one alcohol-dependent subjects meeting admission criteria were randomly assigned to 12 weeks of double-blind treatment with 40 mg nalmefene, 10 mg nalmefene, or placebo, resulting in 7 patients/treatment group. Nalmefene was well tolerated, with no serious adverse drug reactions. The 40 mg group had a significantly lower rate of relapse ( p 0.05), and a greater increase in the number of abstinent days/week ( p 0.09), than the other treatment groups. A significant decrease in the number of drinks/drinking day was noted for both nalmefene groups ( p 0.04), but not for placebo. These results were supported by parallel decreases in ALT. These pilot data provide preliminary support for the hypotheses that nalmefene can be safely given to alcoholics, and that nalmefene may have a role in reducing alcohol consumption and preventing relapse, particularly at the 40 mg level. A full-scale study is underway to confirm these preliminary findings.     

Does melatonin induce apoptosis in MCF‐7 human breast cancer cells in vitro?

Melatonin inhibits proliferation of the estrogen-responsive MCF-7 human breast cancer cells. The objective of this work was to assess whether melatonin not only regulates MCF-7 cell proliferation but also induces apoptosis. In this experiment we used 1,25-dihydroxycholecalciferol (D3) as a positive control because it inhibits MCF-7 cell proliferation and induces apoptosis. MCF-7 cells were cultured with either I nM melatonin, 100 nM D3 or its diluent to determine their effects on cell proliferation, cell viability, cell-cycle phase distribution, population of apoptotic cells, and expression of p53, p21WAF1, bcl-2, bcl-X(L) and bax proteins. After 24 or 48 hr of incubation, both melatonin and D3-treatment significantly decreased the number of viable cells in relation to the controls, although no differences in cell viability were observed between the treatments. The incidence of apoptosis, measured as the population of cells falling in the sub-G1 region of the DNA histogram, or by the TUNEL reaction, was similar in melatonin-treated and control cells whereas, as expected, apoptosis was higher among cells treated with D3 than in controls. The expression of p53 and p21WAF1 proteins significantly increased after 24 or 48 hr of incubation with either melatonin or D3. No significant changes in bcl-2, bcl-XL and bax mRNAs were detected after treatment with melatonin whereas in D3-treated cells, a significant drop in bcl-XL was observed. These data support the hypothesis that melatonin reduces MCF-7 cell proliferation by modulating cell-cycle length through the control of the p53-p21 pathway, but without clearly inducing apoptosis.     

Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction

OBJECTIVES: The aim of this research was to assess the incidence, clinical predictors, and outcome of contrast-induced nephropathy (CIN) after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: Contrast-induced nephropathy is associated with significant morbidity and mortality after PCI. Patients undergoing primary PCI may be at higher risk of CIN because of hemodynamic instability and unfeasibility of adequate prophylaxis. METHODS: In 208 consecutive AMI patients undergoing primary PCI, we measured serum creatinine concentration (Cr) at baseline and each day for the following three days. Contrast-induced nephropathy was defined as a rise in Cr >0.5 mg/dl. RESULTS: Overall, CIN occurred in 40 (19%) patients. Of the 160 patients with baseline Cr clearance >/=60 ml/min, only 21 (13%) developed CIN, whereas it occurred in 19 (40%) of those with Cr clearance <60 ml/min (p < 0.0001). In multivariate analysis, age >75 years (odds ratio [OR] 5.28, 95% confidence interval [CI] 1.98 to 14.05; p = 0.0009), anterior infarction (OR 2.17, 95% CI 0.88 to 5.34; p = 0.09), time-to-reperfusion >6 h (OR 2.51, 95% CI 1.01 to 6.16; p = 0.04), contrast agent volume >300 ml (OR 2.80, 95% CI 1.17 to 6.68; p = 0.02) and use of intraaortic balloon (OR 15.51, 95% CI 4.65 to 51.64; p < 0.0001) were independent correlates of CIN. Patients developing CIN had longer hospital stay (13 +/- 7 days vs. 8 +/- 3 days; p < 0.001), more complicated clinical course, and significantly higher mortality rate (31% vs. 0.6%; p < 0.001). CONCLUSIONS: Contrast-induced nephropathy frequently complicates primary PCI, even in patients with normal renal function. It is associated with higher in-hospital complication rate and mortality. Thus, preventive strategies are needed, particularly in high-risk patients.     

Continuous veno-venous hemofiltration for the treatment of contrast-induced acute renal failure after percutaneous coronary interventions.

Acute renal failure (ARF) requiring hemodialysis after percutaneous coronary interventions (PCI) is a serious complication with poor prognosis. Hemodialysis-induced hypotension may have deleterious cardiovascular effects, especially in high-risk patients. Ultrafiltrate removal and simultaneous fluid replacement with a solution similar to plasma for high-volume controlled hydration can be obtained with hemodynamic stability by continuous veno-venous hemofiltration (CVVH). We prospectively assessed the safety and effectiveness of percutaneous CVVH (Y-shaped double-lumen catheter, circuit originating from and terminating in the femoral vein) in 33 consecutive patients (23 men and 10 women; mean age, 69 +/- 9 years) who, after PCI, developed oligo-anuric ARF, associated in 20 of them with congestive heart failure. All patients received a concomitant infusion of furosemide (500-1000 mg/day) and dopamine (2 microg/kg/min). During CVVH, the average fluid volume replacement and body fluid net reduction were 1000 +/- 247 and 75 +/- 48 ml/hr, respectively. Treatment with CVVH continued for 4.7 +/- 2.7 days and corrected fluid overload in all cases. No patient experienced systemic hypotension or hypovolemia. Diuresis recovered in 32 (97%) patients, who showed a parallel improvement of renal function parameters. One patient required chronic dialysis. In-hospital and 1-year mortality was 9.1% and 27.3%, respectively. In conclusion, our data indicate that CVVH is a safe and effective therapy of radiocontrast-induced ARF following PCI. It temporarily replaces renal function without deleterious cardiovascular effects, allowing the kidney to recover from the nephrotoxic injury. However, despite promising early results, large randomized trials are required to define the role of CVVH in ARF after PCI.     

Effects of interactions between ApoE polymorphisms,alcohol consumption and obesity on age-related trends of blood pressure levels in postmenopausal women: The Bambuì cohort study of aging (1997–2008)

Objectives

To evaluate the effects of interactions between ApoE genotypes, alcohol consumption and obesity on the age-related trends of blood pressure (BP) levels in postmenopausal women.

Study design

A population-based prospective cohort study of all residents in Bambuì, south-eastern Brazil, aged 60 years or older. Repeated BP measurements were obtained in four waves from 851 women who underwent ApoE genotyping at baseline (88.3% of those enrolled), and multi-level random-effects pattern-mixture models were used to evaluate the age-related BP trajectories, while accounting for non-ignorable dropouts/deaths and handling heterogeneities as random parameter variations. The few measurements (2.1%) made during hormone replacement therapy were excluded from the analysis.

Results

Alcohol consumption was associated with high levels of systolic and diastolic BP in an age × genotype-dependent manner only in the non-obese women (BMI < 27 kg/m²). Among those with the ?3/3 genotype, the differences in systolic and diastolic levels between drinkers and non-drinkers estimated at the age of 60 years were respectively 13.7 mmHg (p = 0.022) and 10.7 mmHg (p = 0.002), and disappeared in the older age groups, in which drinking was associated with systolic/diastolic hypertension if the non-obese women were ?4 carriers.

Conclusion

In non-obese postmenopausal women, alcohol consumption is associated with systolic and diastolic hypertension early in those with the ?3/3 ApoE genotype, and late in ?4 carriers. We hypothesize the mediation of androgen hormones and the influence of ApoE genotypes on age at natural menopause. A better understanding of these mechanisms may guide better preventive choices.