Circulating SIRT1 inversely correlates with epicardial fat thickness in patients with obesity.

BACKGROUND AND AIM: Obesity is increasing worldwide and is related to undesirable cardiovascular outcomes. Epicardial fat (EF), the heart visceral fat depot, increases with obesity and correlates with cardiovascular risk. SIRT1, an enzyme regulating metabolic circuits linked with obesity, has a cardioprotective effect and is a predictor of cardiovascular events. We aimed to assess the relationship of EF thickness (EFT) with circulating SIRT1 in patients with obesity. METHODS AND RESULTS: Sixty-two patients affected by obesity and 23 lean controls were studied. Plasma SIRT1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). EFT was measured by echocardiography. Body mass index (BMI), waist circumference, heart rate (HR), blood pressure, and laboratory findings (fasting glucose, insulin, HbA1c, cholesterol, and triglycerides) were assessed. SIRT1 was significantly lower (P = 0.002) and EFT was higher (P < 0.0001) in patients with obesity compared with lean controls. SIRT1 showed a negative correlation with EFT and HR in the obesity group (ρ = -0.350, P = 0.005; ρ = -0.303, P = 0.008, respectively). After adjustment for obesity-correlated variables, multiple linear regression analysis showed that EFT remained the best correlate of SIRT1 (ß = -0.352, P = 0.016). CONCLUSIONS: Circulating SIRT1 correlates with the visceral fat content of the heart. Serum SIRT1 levels might provide additional information for risk assessment of coronary artery disease in patients with obesity.

Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.

PURPOSE: Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. METHODS: Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. RESULTS: At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. CONCLUSIONS: In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body composition improvements attained.

Metabolic or bariatric surgery? Long-term effects of malabsorptive vs restrictive bariatric techniques on body composition and cardiometabolic risk factors.

BACKGROUND: Obesity is an increasing health problem and surgery seems to be the only treatment effective in achieving weight loss without relapse. Among bariatric techniques, many differences exist in terms of weight loss and resolution of comorbidities. Up to now, there are no prospective studies comparing long-term effects of malabsorptive vs restrictive techniques. OBJECTIVE: In this study, cardiometabolic risk factors and body composition changes after malabsorptive biliointestinal bypass (BIBP) and restrictive laparoscopic adjustable gastric banding (LAGB) were compared during a 4-year follow-up. DESIGN: Prospective, case-control and cohort study. PATIENTS: In all, 80 obese subjects, matched for weight and age. Altogether, 40 patients underwent BIBP and 40 underwent LAGB. MEASUREMENTS: Weight, body composition, fasting and post-loading plasma glucose and insulin, homeostatic model assessment index (HOMA-I), lipid profile, blood pressure (BP), erythrocyte sedimentation rate and fibrinogen were monitored at baseline, 12 and 48 months. RESULTS: At 12 months after surgery, a significant reduction in body mass index, total fat mass (FM), trunk FM (trFM), trFM/legs FM (lFM) ratio (trFM/lFM), triglycerides, BP and inflammation markers was observed in both groups. BIBP patients showed a significant reduction in total cholesterol (Tot-C), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), whereas the LAGB group showed a significant increase of HDL-C. A further improvement of all the parameters evaluated was seen in the BIBP group at 48 months after surgery. CONCLUSIONS: Both bariatric procedures exerted positive effects on cardiometabolic risk factors and on weight loss in the population studied, but on the long-term period, HOMA-I, Tot-C/HDL-C ratio and body composition improvements were more evident after BIBP. We conclude that malabsorptive BIBP seems to be more effective than LAGB in treating visceral obesity and its metabolic complications.

Epicardial fat: the role of testosterone and lipid metabolism in a cohort of patients with Klinefelter syndrome.

CONTEXT: Klinefelter syndrome (KS), in which subjects have additional copies of X chromosomes, is the most common male sex chromosome abnormality, with a prevalence of 1 in 660 and an incidence of about 1 in 500-700 newborns. Its sign and symptoms include infertility, generally low testosterone levels, and an increased prevalence of obesity and metabolic syndrome. Epicardial fat thickness (EFT) reflects visceral adiposity rather than general obesity. OBJECTIVE: The aim of this study was to analyze echocardiographic EFT in a cohort of patients with KS in comparison with non-obese and obese euploid controls, and to evaluate its correlation with biochemical parameters. DESIGN, SETTING AND PARTICIPANTS: Two hundred and twenty-one KS patients referred to our Rare Endocrine Diseases clinic and 77 age-matched controls underwent Doppler echocardiography and a full investigation of anthropometric and body composition, Serum levels of total testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), fasting plasma glucose, insulin, cholesterol and triglycerides were obtained. All participants underwent dual energy X-ray absorptiometry (DEXA) scan to assess truncal body fat (TrBF). MAIN OUTCOME MEASURE: EFT, body composition and metabolic parameters in KS patients and how they are affected by genotype. RESULTS: EFT was greater in KS patients than in healthy non-obese (NOb) controls, but lower than in obese (OB) controls. When KS patients were divided into groups (hypogonadal; eugonadal; receiving testosterone replacement therapy [TRT]), EFT was greater in hypogonadal patients than in NOb controls and eugonadal patients, but showed no difference from the OB controls or TRT patients. Hypogonadal patients showed increased TrBF in comparison with NOb controls and eugonadal and TRT patients, and similar TrBF to OB controls. As expected, there was a strong correlation between BMI and EFT in both KS patients and controls (P < 0.0001). In contrast, there was a strong inverse correlation between testosterone and EFT in the control group, but not in KS patients. EFT was significantly correlated with TrBF in both populations (P < 0.0001). Multivariate analyses showed that the major determinants of both EFT and TrBF were BMI and the presence of KS itself. Testosterone and triglycerides were not included as variables in the models. CONCLUSION: EFT in hypogonadal KS subjects was similar to that of the obese eugonadal controls. Even though there was a direct correlation between BMI and EFT in both populations, the influence of TrBF on EFT was stronger. The presence of the supernumerary X chromosome appeared to be one of the strongest determinants of EFT and TrBF, independent of testosterone levels.

Vascular injury, hypertension and coronary artery disease in human immunodeficiency virus infection.

The atherogenic effects of some highly active antiretroviral therapy (HAART) regimens, especially those including protease inhibitors (PI), may synergistically promote the acceleration of cardiovascular disease and increase the risk of death from cardiovascular events even in young HIV-infected people. Along with the endothelial dysfunction associated with visceral fat accumulation and related metabolic alterations of HIV-lipodystrophy syndrome (eg, insulin resistance), vascular injury has been associated with HIV-1 infection itself, with an autoimmune reaction to viral infection (vasculitis) and with a direct action of drugs included in HAART regimens. Clinical studies suggest that HIV-infected patients under PI-including HAART and with preexisting cardiovascular risk factors, should be considered at risk for developing coronary artery disease, and that this risk increases with the time of exposure to HAART. A careful cardiovascular screening and monitoring of HIV-infected patients receiving HAART is needed according to the most recent clinical guidelines.

Management of chronic hepatitis in drug addicts: a systematic review.

Injection drug users constitute the largest group of person at high risk for acquiring chronic hepatitis C, B and Delta. In particular viral, host and environmental factors all seem to favour rapid spread of these infections among drugs addicts. Host factors include behaviours that expose individuals to hepatitis virus such as the shared use of drug preparation, injection equipment and not protected sexual relationship with other drugs users. While in some clinical studies adherence to treatment regimens was often poor and to treat chronic hepatitis in injection drug users was stated as futile, in other controlled clinical studies adherence and sustained biological response to antiviral treatment was slightly lower or similar to that reported in other groups of patients. In this review we describe the epidemiology, diagnosis and treatment of chronic hepatitis C, B and Delta in intravenous drug users.

Cardiac autonomic imbalance in patients with reversible ventricular dysfunction takotsubo cardiomyopathy.

BACKGROUND: Although in reversible takotsubo cardiomyopathy (TC), wall motion generally recovers dramatically within a few weeks, there are few data on changes in autonomic function in this condition. AIM: To investigate cardiac autonomic function in the acute and chronic phases of TC. METHODS: Ten patients with TC (mean age 70.1 +/- 13.7 years) underwent cardiac catheterization on the first hospital day, when left ventricular (LV) ejection fraction (EF) was calculated. A Holter electrocardiographic study was performed within 3 days after the onset of symptoms (0 months) and 3 months after discharge (3 months). The standard deviation of the mean cycle length of normal-normal R-R (NN) intervals over 24 h (SDNN), and the 24-h standard deviation of the mean value of the difference between the NN intervals for each 5-min segment (SDANN), were calculated according to time-area analysis of heart rate variability over 24 h. Frequency domain analysis was also done. RESULTS: Coronary angiography in the acute and chronic phases revealed no significant stenosis in any TC patient. LV wall motion returned to normal in 17.6 +/- 6.4 days. LVEF was 45.7 +/- 8.8% in the acute phase and 69.8 +/- 6.8% after the improvement of wall motion (p < 0.001). Between 0 months and 3 months, SDNN and SDANN improved significantly, from 88.8 +/- 35.5 to 109.5 +/- 33.4 ms (p = 0.01) and from 79.9 +/- 34.7 to 99.3 +/- 40.3 ms (p = 0.03), respectively. No significant changes were observed in frequency domain parameters. DISCUSSION: These results support our previous hypothesis that TC might be caused by neurogenic stunning of the myocardium, due to acute autonomic dysfunction.

Intensity of myocardial expression of inducible nitric oxide synthase influences the clinical course of human immunodeficiency virus-associated cardiomyopathy. Gruppo Italiano per lo Studio Cardiologico dei pazienti affetti da AIDS (GISCA).

BACKGROUND: Increased levels of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) have been reported in patients with dilated cardiomyopathy. We investigated the myocardial expression of TNF-alpha and iNOS in patients with HIV-associated cardiomyopathy (HIV-DCM) compared with patients with idiopathic dilated cardiomyopathy (IDCM). METHODS AND RESULTS: Endomyocardial biopsy specimens from 82 HIV-DCM and 80 IDCM patients were processed for determination of the immunostaining intensity of TNF-alpha and iNOS and for virological examination. Negative controls were derived from autopsy myocardium specimens from 32 HIV-negative patients without known heart disease. The mortality rate for congestive heart failure between groups according to the intensity of iNOS staining was also evaluated. The mean intensity of both TNF-alpha and iNOS staining was greater in patients with HIV-DCM (0.81 and 1.007, respectively) than in patients with IDCM (0.44 and 0.49, respectively) and controls (0.025 and 0.027, respectively). The staining intensity of both TNF-alpha and iNOS was inversely correlated with CD4 count. The staining intensity of iNOS was greater in HIV-DCM patients with HIV/coxsackievirus B3 (CVB3) or with HIV/cytomegalovirus coinfection than in IDCM patients showing infection with CVB3 and adenovirus alone. The staining intensity of iNOS correlated to mortality rate, because it was higher in HIV-DCM patients and, in particular, in those with an optical density unit >1. CONCLUSIONS: Cytokine activation seems to play a significant pathogenetic role in both HIV-DCM and IDCM. In HIV-DCM patients, the state of immunodeficiency may favor the selection of viral variants of increased pathogenicity, influencing the clinical course of cardiomyopathy by enhancement of the inflammatory process.

Reviewing the cardiovascular complications of HIV infection after the introduction of highly active antiretroviral therapy.

Studies published before the introduction of highly active antiretroviral therapy (HAART) have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac disease.The introduction of HAART regimens, by preventing opportunistic infections and reducing the incidence of myocarditis, has reduced the prevalence of HIV-associated cardiomyopathy of about 30% and the prevalence of cardiac involvement of AIDS-associated malignancies of about 50%. However, HAART regimens, especially those including protease inhibitors have been shown to cause, in a high proportion of HIV-infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease (approximately 1.4 cardiac events per 1000 years of therapy according to the Framingham score). A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART according to the most recent clinical guidelines is needed.

Effect of recombinant human granulocyte-macrophage colony-stimulating factor on HIV-related leukopenia: a randomized, controlled clinical study.

OBJECTIVE: To assess the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on white blood cell (WBC) count and on the rate of opportunistic infections in a large and selected population of leukopenic HIV-positive patients compared with non-treated controls. DESIGN: Open-label, randomized, comparative clinical study. SETTING: University hospitals and AIDS centres. PATIENTS AND METHODS: One hundred and twenty-three leukopenic HIV-positive patients received recombinant human GM-CSF (300 microg subcutaneously daily for 1 week, and 150 microg subcutaneously two times weekly for 11 weeks thereafter); the control group comprised 121 non-treated leukopenic HIV-positive patients. A complete blood cell count with differential, platelet count, reticulocyte count, and CD4+ and CD8+ T-cell subset counts were performed in both patient groups at baseline and at weeks 1, 12 and 24. RESULTS: The administration of GM-CSF resulted in a significant increase of WBC count in patients compared with non-treated controls. Total leukocyte count increased by 22% at week 1 and by 65% at week 12 compared with baseline levels; a 20% increase of total leukocyte count was still present at week 24. Increases of neutrophils, eosinophils and monocytes were responsible for the majority of the increase in WBC count. Opportunistic infections occurred in 61.7% of GM-CSF-treated patients and in 72% of the patients of the control group (relative risk, 0.86; 95% confidence interval, 0.72-1.03; P = 0.123). Mild flu-like side-effects were observed in most patients receiving GM-CSF, although they were not sufficiently severe to warrant withdrawal from the study. CONCLUSIONS: GM-CSF was well tolerated and biologically active in leukopenic HIV-positive patients, with a significant, although time-limited, increase of WBC count compared with non-treated patients. The administration of this growth factor should be considered in ameliorating the myelosuppression observed with some cell-cycle-specific antiviral and anti-neoplastic agents.

Clinical course of cardiomyopathy in HIV-infected patients with or without encephalopathy related to the myocardial expression of tumour necrosis factor-alpha and nitric oxide synthase.

OBJECTIVE: To define whether the development of encephalopathy influences the clinical course of HIV-associated cardiomyopathy (HIV-DCM) in relation to the myocardial expression of tumour necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). DESIGN: Prospective study. SETTING: University hospitals and AIDS centres. METHODS: 115 HIV-infected patients with echocardiographic diagnosis of HIV-associated cardiomyopathy (34 with encephalopathy and 81 without encephalopathy) were followed for a mean of 24 +/- 3.2 months. All patients underwent endomyocardial biopsy for determination of myocardial immunostaining intensity of TNF-alpha and iNOS. Cerebrospinal fluid (CSF) from patients with encephalopathy was examined for the presence of viruses. Patients underwent clinical examination every 3 months and echocardiographic examination every 6 months. The intensity of TNF-alpha and iNOS immunostaining was also evaluated on postmortem cerebral tissue of patients who died of congestive heart failure (CHF). RESULTS: A greater impairment of echocardiographic parameters was observed in patients with HIV-associated cardiomyopathy after development of encephalopathy. These parameters tended to worsen progressively during the follow-up period and were inversely correlated with HIV-1 viral load, CD4 cell count, mini mental status score and the intensity of myocardial and cerebral TNF-alpha and iNOS staining. CSF specimens were available in 29 patients with encephalopathy. HIV-1 sequences were detected in CSF of all these patients with cytomegalovirus sequences in two. The mortality rate for CHF was greater among patients with encephalopathy (73% versus 12%). CONCLUSIONS: The development of encephalopathy has an adverse effect on the clinical course of HIV-associated cardiomyopathy. In the relationship between cardiomyopathy and encephalopathy, the activation of iNOS by TNF-alpha may have a significant pathogenetic role in HIV disease.

Pathogenesis of HIV-associated cardiovascular complications.

Reviews and studies published before the introduction of highly active antiretroviral therapy (HAART) have tracked the incidence and course of HIV infection in relation to cardiac illness in both children and adults. The introduction of HAART regimens has significantly modified the course of HIV disease, with longer survival rates and improvement of life quality in HIV-infected people expected. However, early data raised concerns about HAART being associated with an increase in both peripheral and coronary arterial diseases. In this review we discuss HIV-associated cardiovascular complications focusing on pathogenetic mechanisms that could have a role in diagnosis, management, and therapy of these complications in the HAART era.

Interferon alpha-2B and ribavirin in combination for patients with chronic hepatitis C who failed to respond to, or relapsed after, interferon alpha therapy: a randomized trial.

PURPOSE: To assess the efficacy of interferon alpha-2b and ribavirin in combination in the treatment of patients with chronic hepatitis C who had either failed to respond to therapy with interferon alpha (nonresponders), or who had relapsed after interferon therapy (relapsers). SUBJECTS AND METHODS: Four hundred patients with chronic hepatitis C (200 nonresponders and 200 relapsers) were randomly assigned in equal numbers to receive either subcutaneous administration of recombinant interferon alpha-2b (3 million units three times per week) and ribavirin (1,000 to 1,200 mg/daily orally) or interferon alpha-2b alone (6 million units three times per week). Both ribavirin and interferon alpha-2b were given for 24 weeks. The patients were then followed for an additional 24 weeks. RESULTS: At the end of the treatment period, normalization of serum alanine aminotransferase levels and absence of hepatitis C virus RNA were seen in 21% of nonresponders and in 39% of relapsers who were treated with interferon alpha-2b and ribavirin, compared with 5% of nonresponders (P = 0.001) and 9% of relapsers treated with interferon alpha-2b alone (P <0.001). At the end of follow-up, 14% of nonresponders and 30% of relapsers treated with the combination therapy had a sustained response, compared with 1% of nonresponders (P = 0.001) and 5% of relapsers treated with interferon alpha alone (P <0.001). CONCLUSIONS: A 24-week course of treatment with interferon alpha-2b and ribavirin offers a chance of sustained response, whereas retreatment with interferon alpha-2b alone does not give satisfactory results. The role of long-term therapy in inducing prolonged remission remains to be explored.

Early impairment of systolic and diastolic function in asymptomatic HIV-positive patients: a multicenter echocardiographic and echo-Doppler study. The Gruppo Italiano Per lo Studio Cardiologico dei Pazienti Affetti da AIDS.

Human immunodeficiency virus (HIV) possesses an intrinsic cardiopathogenic action that may be detected even in the early stages of HIV disease. To assess an early impairment of systolic and diastolic function in asymptomatic HIV-positive patients (CD4+ > or = 600/mm3), we performed a multicenter echocardiographic and echo-Doppler trial on 1236 asymptomatic NYHA class I HIV-positive patients (885 M and 351 F; mean age 28 years) compared with 1230 healthy subjects (922 M and 308 F; mean age 30 years). The sample size was established considering, as null hypothesis, a difference less than 10% in the values of the principal echocardiographic and echo-Doppler parameters between groups with a 90% statistical power (alpha = 0.01; beta = 0.10). Analysis of echocardiographic and echo-Doppler data revealed a reduction of 19.7% in ejection fraction, an increase of 55.7% in wall motion score, a reduction of 34.6% in the E/A ratio, and an increase of 19.7% in the isovolumetric relaxation time in HIV-positive subjects compared with healthy controls (p < 0.001). Baseline electrocardiographic alterations were observed in 707 (57.2%) HIV-positive subjects and in 169 (13.7%) of the subjects of the control group (p < 0.001). The results of our study have demonstrated that in asymptomatic HIV-positive subjects a significant impairment of systolic and diastolic function may be detected by echocardiographic and echo-Doppler examination, confirming an early involvement of the heart in HIV disease.

Cardiac involvement in the acquired immunodeficiency syndrome: a multicenter clinical-pathological study. Gruppo Italiano per lo Studio Cardiologico dei pazienti affetti da AIDS Investigators.

The heart is frequently involved in the acquired immunodeficiency syndrome (AIDS). This study was planned to assess the prevalence of cardiac involvement in a large and selected population of patients who died of AIDS. Of 440 AIDS patients who underwent autopsy, cardiac involvement was documented in 82 patients. Dilated cardiomyopathy was found in 12 patients; lymphocytic interstitial myocarditis was documented in 30 patients, and in 10 of 12 patients with dilated cardiomyopathy. Inflammatory infiltrate was predominantly composed by CD3+ and CD8+ with a positive staining for major histocompatibility class I in 70% of the cases. Infective endocarditis was documented in 28 patients, pericardial effusion in 53 patients, myocardial Kaposi's sarcoma in 2 patients, myocardial B-cell immunoblastic lymphoma in 1 patient. Sequences of human immunodeficiency virus (HIV) nucleic acid were detected using the technique of in situ hybridization in the myocytes of 29 autopsy patients and in 25 of 29 patients with a positive hybridization signal an active myocarditis was documented. Among them, 7 presented a coinfection with Coxsakievirus group B, 2 with Epstein-Barr virus, and 1 with cytomegalovirus. HIV-associated cardiomyopathy may be related either to a direct action of HIV on the myocardial tissue or to an autoimmune process induced by HIV even in association with other cardiotropic viruses.

Fluconazole vs itraconazole-flucytosine association in the treatment of esophageal candidiasis in AIDS patients. A double-blind, multicenter placebo-controlled study. The Candida Esophagitis Multicenter Italian Study (CEMIS) Group.

STUDY OBJECTIVE: To assess the role and the therapeutic efficacy of fluconazole and itraconazole-flucytosine association compared with placebo, in the treatment of endoscopically diagnosed esophageal candidiasis in a selected population of AIDS patients. DESIGN: Double-blind, placebo-controlled study. SETTING: University Hospitals and AIDS Centers. PATIENTS: Eighty-five HIV-positive patients (53 men and 32 women; mean age, 28 years) at first episode of esophageal candidiasis diagnosed by endoscopy (grades I to II of Kodsi's endoscopic classification and grades I to IIa of Barbaro's clinical classification). All the patients selected for the study provided informed consent. INTERVENTIONS: The patients have been double blindly randomized in 3 groups of patients in relation to pharmacologic therapy: (1) the patients of the first group (n = 30) received fluconazole (3 mg/kg daily orally) and placebo (100 mg/kg/daily orally); (2) the patients of the second group (n = 30) received itraconazole (3 mg/kg daily orally) and flucytosine (100 mg/kg daily orally); and (3) the patients of the third group (n = 25) received placebo (3 mg/kg daily orally) and placebo (100 mg/kg daily orally). After 2 weeks of treatment, the patients previously randomized to receive placebo only were double blindly randomized to receive fluconazole+placebo or itraconazole+flucytosine. To evaluate the efficacy of pharmacologic therapy, clinical and endoscopic examinations were performed at weeks 2 and 4 and at the end of follow-up (3 months). RESULTS: At week 2, endoscopic cure (grade 0) was observed in 68.9% of the fluconazole+placebo group and in 72.4% of the itraconazole+flucytosine group (relative risk, 0.95; 95% confidence interval [CI], 0.68 to 1.33; p = 0.772); partial endoscopic response (grade I) was observed in 22.7% of the placebo group. Clinical cure (grade 0) was observed in 75.8% of fluconazole+placebo group and in 72.4% of itraconazole+flucytosine group (relative risk, 1.05; 95% CI, 0.77 to 1.42; p = 0.764), with a difference statistically significant for both treatments in comparison to placebo group (p < 0.001). Partial clinical response (grade I) was observed in 27.3% of the placebo group. At the end of follow-up, endoscopic cure was observed in 89.8% of the fluconazole+placebo group and in 94.8% of the itraconazole+flucytosine group (relative risk, 0.97; 95% CI, 0.83 to 1.08; p = 0.695). Clinical cure was observed in 94.8% of the fluconazole+placebo group and in 97.3% of the itraconazole+flucytosine group (relative risk, 0.97; 95% CI, 0.89 to 1.07; p = 0.981). CONCLUSIONS: The results of this study have demonstrated that both fluconazole and itraconazole+flucytosine association are efficacious in short-term treatment of esophageal candidiasis in AIDS patients with a statistically significant difference in comparison to placebo. Both therapeutic regimens demonstrated a good therapeutic efficacy, without statistically significant difference, between them, in the rate of endoscopic and clinical cure. Itraconazole+flucytosine association may represent an alternative therapeutic regimen for patients with fluconazole-resistant Candida esophagitis.

Addition reactions of aldehydes to lithium enolates of 1,3-dioxolan-4-ones: a configurational reassessment

The results for the addition reactions of chiral lithium (2S)-enolates of 1,3-dioxolan-4-ones to aldehydes and to acetophenone, yielding the corresponding dioxolanone alcohols have been revised. The results reported herein differ from those reported in the literature, both in product distribution and in the stereochemical assignment of the products. In fact, in several cases no stereocontrol was observed at the C5 carbon atom of the lithium enolate. The (2S,5R,1'S)/(2S,5R,1'R) stereochemistry was also reassessed for several dioxolanone alcohols. The major conformers are considered to have an intramolecular hydrogen-bonded five-membered ring structure instead of the six-membered ring structure previously suggested for cyclic dioxolanone alcohols.

Pathogenesis of HIV-associated cardiomyopathy.

Reviews and studies published before the introduction of highly active antiretroviral therapy (HAART) regimens have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac illness in both children and adults. HAART regimens have significantly modified the course of HIV disease, with longer survival rates and improvement of life quality in HIV+ subjects expected. However, early data raised concerns about HAART's being associated with an increase in both peripheral and coronary arterial diseases. A variety of potential etiologies have been postulated in HIV-related heart disease, including myocardial infection with HIV itself, opportunistic infections, viral infections, autoimmune response to viral infection, drug-related cardiotoxicity, nutritional deficiencies, and prolonged immunosuppression. In this review article we discuss HIV-associated cardiovascular complications, focusing on pathogenetic mechanisms that may play a role in diagnosis, management, and therapy of these complications.

Individual knowledge of emotions in asthmatic children.

Twenty male asthmatic children (ages 9-11) and their controls were interviewed regarding their concept of emotion using the interview format developed by Harris et al. (1981). The purpose of the study was to examine the asthmatic children's views on the nature and effects of happiness, anger and fear, together with strategies of self-control. The results indicate that healthy and asthmatic children have a different individual view of emotion. The most relevant finding concerns the different way in which healthy and asthmatic children consider fear: the most frequent view of fear in healthy children is similar to a behaviouristic model of emotion, while asthmatic children express a notion very similar to a cognitive model. Regarding anger, almost all healthy children believe themselves capable of exerting self-control whether on the inner mental components or on its outer expression, where a change of direction of mental processes is the only way asthmatic children see to modify their anger. The implications of these findings both for a description of asthmatic personality and therapy are outlined.

Role of Ca++ antagonists (nifedipine) in the long-term prognosis of hypertensive patients with previous history of myocardial infarction.

One hundred and twenty-two patients suffering from slight or moderate essential arterial hypertension with a previous history of myocardial infarction were selected for inclusion in this study. Patients were divided into two groups of 61 according to the type of anti-hypertensive therapy received. Patients in Group 1 received nifedipine (30 mg p.d.), while patients in Group 2 were treated using other anti-hypertensive therapy (diuretics, alpha-methyldopa, clonidine, indapamide). At the end of the follow-up period, which lasted 5 years, a statistically significant improvement in the following factors was observed in Group 1 in comparison to the control group: (a) an improved response of both SBP (p less than 0.001) and DBP (p less than 0.001) levels to anti-hypertensive therapy; (b) a more significant diminution in the thickness of the interventricular septum (p less than 0.001) and the posterior wall of the left ventricle (p less than 0.001) assessed using ultrasonography; (c) a reduced number of cases of post-infarction angina (p less than 0.05); (d) fewer cases of recurrent infarction (p less than 0.05); (e) fewer deaths as a result of re-infarction (p less than 0.01). These results confirm that the vascular and cardioprotective effects of nifedipine give a good long-term outcome in hypertensive patients with a previous history of myocardial infarction.