Estudio de la repetición del pentanucleótido CCTTT en el gen de la sintasa inducible del óxido nítrico en pacientes con hipertensión arterial pulmonar

Introduction

One of the pathways involved in pulmonary arterial hypertension (PAH) is the nitric oxide (NO) pathway. A polymorphism in the inducible NO synthase (NOS2) gene has been described, consisting of the CCTTT pentanucleotide repeat, which causes a reduction in NO production. The aim of this study was to determine if this polymorphism increases susceptibility to developing PAH.

Methods

Sixty four patients with a diagnosis of PAH groups i and iv and 50 healthy controls were compared. DNA genotyping of the samples for this polymorphism was performed using PCR. The distribution between both groups was compared and correlated with clinical and haemodynamic parameters and therapeutic response.

Results

A significantly different distribution was observed in the number of repeats between patients and controls (P < .0001). When the samples were categorised by short forms (both alleles with less than 12 repeats) and long forms (≥ 12 repeats), it was observed that the former had an almost 4-fold risk of developing PAH (odds ratio: 3.83; 95% CI: 1.19-12.32, P = .024). There were no differences between the most common types of PAH, either in therapeutic response or survival. There was no correlation between haemodynamic parameters and the number of repeats in the patients, and only a weak correlation with systolic PAH.

Conclusions

There are significant differences in the distribution of the NOS2 promotor CCTTT polymorphism between patients with PAH and the healthy population. A minor CCTTT pentanucleotide repeat in the NOS2 gene may increase the risk of developing PAH.     

Marcadores pronósticos en pacientes con gammapatía monoclonal de significado incierto

Objective

The assessment of prognostic biomarkers in monoclonal gammopathies of uncertain significance (MGUS) requires using large cohorts and long follow-ups, due to the low rate of conversion to multiple myeloma (MM). The aim of this article is to develop a model that allows smaller cohorts and shorter follow-ups to be used with high reliability.

Patients and methods

A total of 64 MGUS patients were studied and followed-up prospectively for 6 ± 0.24 years. Patients were classified as evolving or non-evolving, depending on whether the monoclonal protein levels increased or not over time. The risk of conversion to MM was tested based on these phenotypes, and whether the factors that predict conversion to MM are also associated with the appearance of an evolving phenotype.

Results

Eleven patients showed an evolving phenotype, and 53 a non-evolving one. All patients who converted to MM previously showed evolving phenotype (P = .003). At diagnosis, evolving phenotype associated with monoclonal gammopathies of IgA isotype (27 vs. 9%), monoclonal IgG levels above 1,500 mg/dl (P = .007, OR 9.8) and altered kappa/lambda ratios (P = .001, OR 11.7).

Conclusions

Risk factors for developing an evolving phenotype in MGUS patients are the same as those already described for the development of MM. These data show the validity of the evolving/non-evolving model to study markers to predict the outcome of MGUS patients, and confirm the role of the levels of monoclonal IgG and the light chains ratio in the prognosis of this disease.     

B-cell growth factor receptor expression and B-cell growth factor response of leukemic B cell precursors and B lineage lymphoid progenitor cells

The purpose of this study was to analyze the expression of B cell growth factor (BCGF) receptors and to elucidate the biologic effects of biochemically purified natural BCGF at the B cell precursor stage of human B lineage lymphoid differentiation. The specific binding of radioiodinated high-mol-wt BCGF (125I-HMW-BCGF) and low-molecular-wt BCGF (125I-LMW-BCGF) to fresh marrow blasts from B cell precursor acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated BCGF molecules bound per blast ranged from undetectable to 24.3 X 10(3) for HMW-BCGF, and from 11.5 X 10(3) to 457.8 X 10(3) for LMW-BCGF. In 3H-TdR incorporation assays, 75% of cases showed a significant response to LMW-BCGF with a median stimulation index of 9.3. By comparison, only 33% of cases showed a significant response to HMW-BCGF with a median stimulation index of 2.4. Subsequently, B cell precursor colony assays were performed to assess and compare the biologic effects of BCGF on leukemic B lineage lymphoid progenitor cells. Among 28 cases studied, 57% responded to both HMW-BCGF and LMW-BCGF, 21% responded only to LMW-BCGF, and the remaining cases showed no proliferative response to either growth factor. The response patterns of virtually pure populations of FACS- sorted leukemic B cell precursors were essentially identical to the proliferative responses of unsorted leukemic B-cell precursors. Synergistic effects between HMW-BCGF and LMW-BCGF were observed in 80% of the cases that responded to both. The numbers of cell-bound radioiodinated BCGF molecules, the stimulation indices, as well as the number of B cell precursor colonies in BCGF-stimulated cultures showed a marked interpatient variation. Patients with structural chromosomal abnormalities (SCAs) involving 12p11-13 or patients with a Philadelphia chromosome showed a greater HMW-BCGF response at the level of leukemic progenitor cells than did other patients (P = .02). The LMW-BCGF response was significantly greater for patients with SCA than for patients without SCA (P = .04). The response of leukemic progenitor cells to HMW-BCGF or LMW-BCGF did not correlate with sex, age, disease status, FAB morphology, WBC at diagnosis, or immunophenotype. To our knowledge, this study represents the first detailed analyses of BCGF receptor expression and BCGF effects in B cell precursor ALL. The data presented provide direct evidence for the expression of functional receptors for both HMW-BCGF and LMW-BCGF in B cell precursor ALL.     

Impaired coronary flow reserve in patients with non-ischemic heart failure

INTRODUCTION AND OBJECTIVES: Coronary flow reserve (CFR) is impaired not only in ischemic heart disease, but also in cardiac diseases that may or may not course with heart failure. The aim of the present study was to determine if the severity of heart failure can influence CFR impairment. METHODS: Forty patients with non-ischemic heart disease and heart failure were studied 41 times. Four groups were established: 1. 10 patients in functional class III-IV; 2. 10 patients in functional class II not taking beta-blockers; 3. 11 patients in class II treated with carvedilol, and 4. 10 patients in class I. These patients had a history of heart failure and systolic dysfunction. Myocardial blood flow (MBF) was measured with positron emission tomography (PET) and N-13 ammonia at rest (r) and during adenosine triphosphate (ATP) infusion. RESULTS: MBF and CFR were significantly higher in group 4 (1.95 0.58 and 2.40 0.95 ml/min/g) than in group 1 (1.02 0.52 and 1.46 0.48 ml/min/g). CFR tended to be higher in groups 2 (1.73 0.72), and 3 (1.89 0.75) vs group 1. No significant correlation was found between CFR and the following variables: age, systolic blood pressure, ventricular mass index, ventricular volume indexes, and ejection fraction. CONCLUSIONS: Coronary microvascular function is impaired in non-ischemic heart failure, and the impairment is related to functional class, regardless of the underlying responsible heart disease.     

Increase in Hepatitis A Cases Linked to Imported Strains to Rio de Janeiro,Brazil: A Cross-Sectional Study

This study aims to evaluate the epidemiological and molecular features associated with HAV transmission in adults in Rio de Janeiro during a period of increased registered cases of HAV (2017–2018). Socio-epidemiological data and serum samples from anti-HAV IgM+ individuals were obtained. HAV RNA was RT-PCR amplified and sequenced for further phylogenetic and phylogeographic analyses. From fifty-two HAV IgM+ individuals, most were men (78.85%; p = 0.024), aged 20–30 years old (84.61%; p < 0.001), resided in the Rio de Janeiro north zone (31/52; 59.62%; p = 0.001), and are men who have sex with men (MSM) (57.69%; p = 0.002). Sexual practices were more frequent (96%) than others risk factors (food-borne (44%), water-borne (42.31%), and parenteral (34.62%)). Individuals who traveled to endemic regions had a 7.19-fold (1.93–36.04; p < 0.01) increased risk of HAV. Phylogenetic analysis revealed four distinct clades of subgenotype IA, three of them comprised sequences from European/Asian MSM outbreaks and one from Brazilian endemic strains. Bayesian Inference showed that the imported strains were introduced to Brazil during large mass sportive events. Sexual orientation and sexual practices may play a role in acquiring HAV infection. Public policies targeting key populations must be implemented to prevent further dissemination of HAV and other STIs.     

Left‐handed musicians show a higher probability of atypical cerebral dominance for language

Music processing and right hemispheric language lateralization share a common network in the right auditory cortex and its frontal connections. Given that the development of hemispheric language dominance takes place over several years, this study tested whether musicianship could increase the probability of observing right language dominance in left‐handers. Using a classic fMRI language paradigm, results showed that atypical lateralization was more predominant in musicians (40%) than in nonmusicians (5%). Comparison of left‐handers with typical left and atypical right lateralization revealed that: (a) atypical cases presented a thicker right pars triangularis and more gyrified left Heschl's gyrus; and (b) the right pars triangularis of atypical cases showed a stronger intra‐hemispheric functional connectivity with the right angular gyrus, but a weaker interhemispheric functional connectivity with part of the left Broca's area. Thus, musicianship is the first known factor related to a higher prevalence of atypical language dominance in healthy left‐handed individuals. We suggest that differences in the frontal and temporal cortex might act as shared predisposing factors to both musicianship and atypical language lateralization.     

Chagas disease reactivation in rheumatologic patients: association with immunosuppressive therapy and humoral response

Clinical Rheumatology - Evidence for Chagas disease reactivation (CDR) in rheumatologic patients under rheumatologic treatments (RTs) is scarce. To screen and follow-up patients with rheumatic...