Azithromycin does not prevent six-month myointimal proliferation but attenuates the transient systemic inflammation occurring after coronary stenting

Stent implantation produces a systemic increase of inflammatory markers that correlates with Chlamydophila pneumoniae infection in atherosclerotic plaque. We performed a clinical intervention study to investigate the effect of antibiotic treatment on 6-month follow-up angiographic minimal luminal diameter after stenting. Ninety patients were randomly assigned to oral azithromycin or placebo in a double-blinded and randomized fashion. Medication was initiated 2 weeks before a pre-scheduled stenting procedure and maintained 12 weeks thereafter. Angiographic outcomes were evaluated by a six-month follow-up angiography and laboratorial parameters were accessed by blood sampling 2 weeks before stenting, within the first 24 h after procedure and additional samples after four weeks and 6 months. Minimal luminal diameter (1.76 +/- A 0.56 mm Vs. 1.70 +/- A 0.86 mm; P = 0.7), restenosis rate, diameter stenosis, late loss, and binary restenosis rates were comparable in placebo and azithromycin group in the 6 months follow-up. Serum levels of C-reactive protein presented a three fold significant increase in the control group one day after stenting but did not change in the azithromycin group (8.5 [3.0;16.4] Vs. 2.9 [1.7;6.6]-median [25;75 percentile] P < 0.01). Azithromycin does not improve late angiographic outcomes but attenuates the elevation of C-reactive protein levels after stenting, indicating an anti-inflammatory effect.

Risk factors for Chagas` disease reactivation after heart transplantation

Background: Chagas` disease is the illness caused by the protozoan Trypanosoma cruzi and it is still endemic in Latin America. Heart transplantation is a therapeutic option for patients with end-stage Chagas` cardiomyopathy. Nevertheless, reactivation may occur after transplantation, leading to higher morbidity and graft dysfunction. This study aimed to identify risk factors for Chagas` disease reactivation episodes. Methods: This investigation is a retrospective cohort study of all Chagas` disease heart transplant recipients from September 1985 through September 2004. Clinical, microbiologic and histopathologic data were reviewed. Statistical analysis was performed with SPSS (version 13) software. Results: Sixty-four (21.9%) patients with chronic Chagas` disease underwent heart transplantation during the study period. Seventeen patients (26.5%) had at least one episode of Chagas` disease reactivation, and univariate analysis identified number of rejection episodes (p = 0.013) and development of neoplasms (p = 0.040) as factors associated with Chagas` disease reactivation episodes. Multivariate analysis showed that number of rejection episodes (hazard ratio = 1.31; 95% confidence interval [CI]: 1.06 to 1.62; p = 0.011), neoplasms (hazard ratio = 5.07; 95% CI: 1.49 to 17.20; p = 0.009) and use of mycophenolate mofetil (hazard ratio = 3.14; 95% CI: 1.00 to 9.84; p = 0.049) are independent determinants for reactivation after transplantation. Age (p = 0.88), male gender (p = 0.15), presence of rejection (p = 0.17), cytomegalovirus infection (p = 0.79) and mortality after hospital discharge (p = 0.15) showed no statistically significant difference. Conclusions: Our data suggest that events resulting in greater immunosuppression status contribute to Chagas` disease reactivation episodes after heart transplantation and should alert physicians to make an early diagnosis and perform pre-emptive therapy. Although reactivation led to a high rate of morbidity, a low mortality risk was observed.

Endostatin- and interleukin-2-expressing retroviral bicistronic vector for gene therapy of metastatic renal cell carcinoma

Background Metastatic renal cell carcinoma (mRCC) is one of the most treatment-resistant malignancies. Despite all new therapeutic advances, almost all patients develop resistance to treatment and cure is rarely seen. In the present study, we evaluated the antitumor effect of a bicistronic retrovirus vector encoding both endostatin (ES) and interleukin (IL)-2 using an orthotopic metastatic RCC mouse model. Methods Balb/C-bearing Renca cells were treated with NIH/3T3-LendIRES-IL-2-SN cells. In the survival studies, mice were monitored daily until they died. At the end of the in vivo experiment, serum levels of IL-2 and ES were measured, the lung was weighed, and the number of metastatic nodules, nodule area, tumor vessels and proliferation of tumor-infiltrating Renca cells were determined. Results Inoculation of NIH/3T3-LendIRES-IL-2-SN cells resulted in an increase in ES and IL-2 levels in the treated group (p < 0.05). There was a significant decrease in lung wet weight, lung nodule area and tumor vessels in the treated group compared to the control group (p < 0.001). The proliferation of Renca cells in the bicistronic-treated group was significantly reduced compared to the control group (p < 0.05). Kaplan-Meier survival curves showed that the probability of survival was significantly higher for mice submitted to bicistronic therapy (log-rank test, p = 0.0016). Bicistronic therapy caused an increase in the infiltration of CD4, CD4 interferon (IFN)gamma-producing, CD8, CD8 IFN gamma-producing and natural killer (CD49b) cells. Conclusions Retroviral bicistronic gene transfer led to the secretion of functional ES and IL-2 that was sufficiently active to: (i) inhibit tumor angiogenesis and tumor cell proliferation and (ii) increase the infiltration of immune cells (C) Copyright. 2011 John Wiley & Sons, Ltd.

Accuracy of store-and-forward diagnosis in leproy

Telemedicine might increase the speed of diagnosis for leprosy and reduce the development of disabilities. We compared the accuracy of diagnosis made by telemedicine with that made by in-person examination. The cases were patients with suspected leprosy at eight public health clinics in outlying areas of the city of Sao Paulo. The case history and clinical examination data, and at least two clinical images for each patient, were stored in a web-based system developed for teledermatology. After the examination in the public clinic, patients then attended a teaching hospital for an in-person examination. The benchmark was the clinical examination of two dermatologists at the university hospital. From August 2005 to April 2006, 142 suspected cases of leprosy were forwarded to the website by the doctors at the clinics. Of these, 36 cases were excluded. There was overall agreement in the diagnosis of leprosy in 74% of the 106 remaining cases. The sensitivity was 78% and the specificity was 31%. Although the specificity was low, the study suggests that telemedicine may be a useful low-cost method for obtaining second opinions in programmes to control leprosy.

A Prospective Study of Conventional and Expanded Coagulation Indices in Predicting Ulcer Bleeding After Variceal Band Ligation

BACKGROUND & AIMS: There is controversy over whether coagulation status predicts bleeding caused by ulceration after esophageal varices band ligation (EVL). METHODS: EVL was performed for primary (n = 45) or secondary (n = 105) prophylaxis in 150 patients with cirrhosis (Child A, n = 74, 49%; Child B, n = 42, 28%; Child C, n = 34, 23%). International normalized ratio (INR) and platelet counts were assessed in all. In 92 patients, levels of factor V, fibrinogen, D-dimer, protein C and protein S, von Willebrand factor, and thromboelastography (TEG) were assessed. Platelet count < 50 x 10(3)/mm(3) and INR > 1.5 were considered high-risk cutoff for bleeding. Conversely, platelet count >= 50 x 10(3)/mm(3) with INR <= 1.5 were safe cutoffs. RESULTS: Overall, 11 patients (7.3%) had post-EVL ulcer bleeding. Bleeding occurred in S patients with Child A/B (4.3%) and 6 patients with Child C (17%) (P = .0174 for Child A/B versus Child C). Eight patients with bleeding were among the 110 below the cutoff for INR and platelet count, whereas only 3 of the patients with bleeding were among the 40 patients with purported high-risk values (P = 1.0). Among the 92 patients with expanded coagulation tests, bleeding occurred in S. There was no difference in any of the coagulation parameters, including overall TEG patterns, between patients who did and did nor bleed. CONCLUSIONS: Post-EVL ulcer bleeding was associated with Child C status but not with conventional or expanded coagulation indices in cirrhotic patients without renal failure or infection undergoing elective EVL. These results call into question the common use of prophylactic procoagulants in the elective setting.

ASPM gene expression in medulloblastoma

Medulloblastomas are the most common malignant tumors of the central nervous system in childhood. The incidence is about 19-20% between children younger than 16 years old with peak incidence between 4 and 7 years. Despite its sensibility to no specific therapeutic means like chemotherapy and radiotherapy, the treatment is very aggressive and frequently results in regression, growth deficit, and endocrine dysfunction. From this point of view, new treatment approaches are needed such as molecular targeted therapies. Studies in glioblastoma demonstrated that ASPM gene was overexpressed when compared to normal brain and ASPM inhibition by siRNA-mediated inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM gene as a potential molecular target in glioblastoma. The aim of this work was to evaluate ASPM expression in medulloblastoma fragment samples, and to compare the results with the patient clinical features. Analysis of gene expression was performed by quantitative PCR real time using SYBR Green system in tumor samples from 37 children. The t test was used to analyze the gene expression, and Mann-Whitney test was performed to analyze the relationship between gene expressions and clinical characteristics. Kaplan-Meier test evaluated curve survival. All samples overexpressed ASPM gene more than 40-fold. However, we did not find any association between the overexpressed samples and the clinical parameters. ASPM overexpression may modify the ability of stem cells to differentiate during the development of the central nervous system, contributing to the development of medulloblastoma, a tumor of embryonic origin from cerebellar progenitor cells.

Vascular diseases and old age mental disorders: an update of neuroimaging findings

Purpose of review To review neuroimaging findings that have been reported in samples of patients with cardiovascular disorders and their association with the onset of Alzheimer`s disease, vascular dementia, depression and bipolar disorder in the elderly and to highlight the implications of these findings to the knowledge about the pathophysiology of psychiatric disorders in old age, as well as their potential clinical implications. Recent findings Vascular risk factors, such as hypertension, diabetes, dyslipidemia, smoking habits and heart failure, have all been associated with signs of cerebrovascular dysfunction, including structural MRI findings of signal hyperintensities, lacunes and stroke and functional imaging findings of brain regional hypoperfusion and hypometabolism. Such brain abnormalities have been found to increase the risk of onset of psychiatric disorder (depression, bipolar and dementia) in old age. Summary As vascular risk factors are potentially modifiable when detected in midlife, the early characterization of brain changes associated with the presence of cardiovascular diseases holds promise to afford clinical applications in psychiatry, providing new perspectives for the prevention of old age psychiatric disorders.

Increased rates of white matter hyperintensities in late-onset bipolar disorder

Objectives: Magnetic resonance imaging (MRI) studies have reported an increased frequency of white matter hyperintensities (WMH) in association with late-onset (LO) depression, and this has supported the notion that vascular-related mechanisms may be implicated in the pathophysiology of LO mood disorders. Recent clinical studies have also suggested a link between LO bipolar disorder (LO-BD) and cerebrovascular risk factors, but this has been little investigated with neuroimaging techniques. In order to ascertain whether there could be a specific association between WMH and LO-BD, we directly compared WMH rates between LO-BD subjects (illness onset 60 years), early-onset BD subjects (EO-BD, illness onset < 60 years), and elderly healthy volunteers. Methods: T2-weighted MRI data were acquired in LO-BD subjects (n = 10, age = 73.60 +/- 4.09), EO-BD patients (n = 49, age = 67.78 +/- 4.44), and healthy subjects (n = 24, age = 69.00 +/- 7.22). WMH rates were assessed using the Scheltens scale. Results: There was a greater prevalence of WMH in LO-BD patients relative to the two other groups in the deep parietal region (p = 0.018) and basal ganglia (p < 0.045). When between-group comparisons of mean WMH scores were conducted taking account of age differences (ANCOVA), there were more severe scores in LO-BD patients relative to the two other groups in deep frontal and parietal regions, as well as in the putamen (p < 0.05). Conclusions: Our results provide empirical support to the proposed link between vascular risk factors and LO-BD. If extended in future studies with larger samples, these. findings may help to clarify the pathophysiological distinctions between bipolar disorder emerging at early and late stages of life.

Hypotension caused by therapeutic doses of venlafaxine: case report and proposed pathophysiological mechanisms

Although venlafaxine is usually associated with modest increases in blood pressure and not so often clinical hypertension, there are a few reported cases of hypotension related to overdoses of this specific antidepressant. The case study of a young female patient with a history of Major Depressive Disorder who initiated treatment with venlafaxine 75 mg/day and developed hypotension when the dosage was titrated up to 225 mg/day is described. The patient did not present comorbid diseases nor use other medication. A temporal association and a dose-dependent relationship between the hypotension and the use of venlafaxine is shown. To the best of the knowledge of the authors, this is the first case report that specifically associates regular doses of venlafaxine with the presence of hypotension. A pathophysiological mechanism is proposed, involving the participation of presynaptic alpha2-adrenergic receptors and the presence of a possible genetic polymorphism of cytochrome P4502D6, which is associated with lower drug metabolization, to explain the relationship between venlafaxine in regular dosage and development of hypotension.

Cybertutor: a teaching tool in Dermatology

It was developed a teaching tool in Dermatology for undergraduate medical students, using an interactive website, the Cybertutor. Clinical cases, lectures and updated bibliography were selected. Photographies of dermatological lesions were taken from ambulatory patients. The topics of the lectures were based on the current curriculum of the Federal University of Rio Grande do Sul. The Cybertutor is a dynamic and modern teaching tool, allowing constant innovation.

Comparison of language impairment in late-onset depression and Alzheimer`s disease

Objectives: Depression and dementia are highly prevalent in the elderly. Language impairment is an inherent component of Alzheimer`s disease (AD), which can also be encountered in depressed patients. The aim of this study wasto compare the profiles of language abilities in late-onset depression and mild AD groups. Methods: We studied 25 patients with late-onset depression (mean age 73.6 +/- 6.6 years; schooling 9.1 +/- 5.7 years) and 30 patients with mild AD (77.6 +/- 5.4 years; 7.5 +/- 7.1 years) using the Arizona Battery for Communication Disorders of Dementia (ABCD), compared to a group of 30 controls (73.8 +/- 5.8 years; 9.1 +/- 5.4 years). Cut-off scores to discriminate between Controls x Depression and Depression x AD were determined. Results: Depressed patients` scores were similar to AD in confrontation naming, concept definition, following commands, repetition and reading comprehension (sentence). Episodic memory and mental status subtests were useful in differentiating depressed patients from AD, a result that was reproduced when using analysis of covariance to control for the effect of age in the same subtests (p = 0.01 and 0.04, respectively). Conclusion: Language impairment resembling AD was found in the aforementioned language subtests of the ABCD in elderly depressed patients; the mental status and episodic memory subtests were useful to discriminate between AD and depression. The ABCD has proven to be a suitable tool for language evaluation in this population and should aid in the differentiation of AD and pseudodementia (as that of depression).

Phenolics and Antioxidant Properties of Fruit Pulp and Cell Wall Fractions of Postharvest Banana (Musa acuminata Juss.) Cultivars

Banana fruits are important foods, but there have been very few studies evaluating the phenolics associated with their cell walls. In the present study, (+) catechin, gallocatechin, and (-) epicatechin, as well as condensed tannins, were detected in the soluble extract of the fruit pulp; neither soluble anthocyanidins nor anthocyanins were present. In the soluble cell wall fraction, two hydroxycinnamic acid derivatives were predominant, whereas in the insoluble cell wall fraction, the anthocyanidin delphinidin, which is reported in banana cell walls for the first time, was predominant. Cell wall fractions showed remarkable antioxidant capacity, especially after acid and enzymatic hydrolysis, which was correlated with the total phenolic content released after the hydrolysis of the water-insoluble polymer, but not for the posthydrolysis water-soluble polymer. The acid hydrolysis released various monosaccharides, whereas enzymatic hydrolysis released one peak of oligosaccharides. These results indicate that banana cell walls could be a suitable source of natural antioxidants and that they could be bioaccessible in the human gut.

Allergic rhinitis in the child and associated comorbidities

Allergic rhinitis (AR) typically presents after the second year of life, but the exact prevalence in early life is unknown. AR affects 10-30% of the population, with the greatest frequency found in children and adolescents. It appears that the prevalence has increased in the pediatric population. As the childs` immune system develops between the 1st and 4th yr of life, those with an atopic predisposition begin to express allergic disease with a clear Th(2) response to allergen exposure, resulting in symptoms. In pediatric AR, two or more seasons of pollen exposure are generally needed for sensitization, so allergy testing to seasonal allergens (trees, grasses, and weeds) should be conducted after the age of 2 or 3 years. Sensitization to perennial allergens (animals, dust mites, and cockroaches) may manifest several months after exposure. Classification of AR includes measurement of frequency and duration of symptoms. Intermittent AR is defined as symptoms for < 4 days/wk or < 4 consecutive weeks. Persistent AR is defined as occurring for more than 4 days/wk and more than 4 consecutive weeks. AR is associated with impairments in quality of life, sleep disorders, emotional problems, and impairment in activities such as work and school productivity and social functioning. AR can also be graded in severity - either mild or moderate/severe. There are comorbidities associated with AR. The chronic effects of the inflammatory process affect lungs, ears, growth, and others. AR can induce medical complications, learning problems and sleep-related complaints, such as obstructive sleep apnea syndrome and chronic and acute sinusitis, acute otitis media, serous otitis media, and aggravation of adenoidal hypertrophy and asthma.

Verbal fluency in the detection of mild cognitive impairment and Alzheimer`s disease among Brazilian Portuguese speakers: the influence of education

Background: Verbal fluency (VF) tasks are simple and efficient clinical tools to detect executive dysfunction and lexico-semantic impairment. VF tasks are widely used in patients with suspected dementia, but their accuracy for detection of mild cognitive impairment (MCI) is still under investigation. Schooling in particular may influence the subject`s performance. The aim of this study was to compare the accuracy of two semantic categories (animals and fruits) in discriminating controls, MCI patients and Alzheimer`s disease (AD) patients. Methods: 178 subjects, comprising 70 controls (CG), 70 MCI patients and 38 AD patients, were tested on two semantic VF tasks. The sample was divided into two schooling groups: those with 4-8 years of education and those with 9 or more years. Results: Both VF tasks - animal fluency (VFa) and fruits fluency (VFf) - adequately discriminated CG from AD in the total sample (AUC = 0.88 +/- 0.03, p < 0.0001) and in both education groups, and high educated MCI from AD (VFa: AUC = 0.82 +/- 0.05, p < 0.0001; VFf: AUC = 0.85 +/- 0.05, p < 0.0001). Both tasks were moderately accurate in discriminating CG from MCI (VFa: AUC = 0.68 +/- 0.04, p < 0.0001 - VFf:AUC = 0.73 +/- 0.04, p < 0.0001) regardless of the schooling level, and MCI from AD in the total sample (VFa: AUC = 0.74 +/- 0.05, p < 0.0001; VFf: AUC = 0.76 +/- 0.05, p < 0.0001). Neither of the two tasks differentiated low educated MCI from AD. In the total sample, fruits fluency best discriminated CG from MCI and MCI from AD; a combination of the two improved the discrimination between CG and AD. Conclusions: Both categories were similar in discriminating CG from AD; the combination of both categories improved the accuracy for this distinction. Both tasks were less accurate in discriminating CG from MCI, and MCI from AD.

GB virus type C infection modulates T-cell activation independently of HIV-1 viral load

Background: Many clinical studies have suggested a beneficial effect of GB virus type C (GBV-C) on the course of HIV-1 infection, but the mechanisms involved in such amelioration are not clear. As recent evidence has implicated cellular activation in HIV-1 pathogenesis, we investigated the effect of GBV-C viremia on T-cell activation in early HIV-1 infection. Methods: Forty-eight recently infected HIV-1 patients (23 GBV-C viremic) were evaluated for T-cell counts, expanded immunophenotyping GBV-C RNA detection, and HIV-1 viral load. Nonparametric univariate and multivariate analyses were carried out to identify variables associated with cellular activation, including GBV-C status, HIV-1 viral load, T lymphocyte counts, and CD38 and chemokine (C-C motif) receptor 5 (CCR5) surface expression. Finding: We not only confirmed the positive correlation between HIV-1 viral load and the percentage of T cells positive for CD38(+)CD8(+) but also observed that GBV-C viremic patients had a lower percentage of T cells positive for CD38(+)CD4(+), CD38(+)CD8(+), CCR5(+)CD4(+), and CCR5(+)CD8(+) compared with HIV-1-infected patients who were not GBV-C viremic. In regression models, GBV-C RNA(+) status was associated with a reduction in the CD38 on CD4(+) or CD8(+) T cells and CCR5(+) on CD8(+) T cells, independent of the HIV-1 viral load or CD4(+) and CD8(+) T-cell counts. These results were also supported by the lower expression of CD69 and CD25 in GBV-C viremic patients. Interpretation: The association between GBV-C replication and lower T-cell activation may be a key mechanism involved in the protection conferred by this virus against HIV-1 disease progression to immunodeficiency in HIV-1-infected patients. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins