Lack of evidence for monosomy 1p36 in patients with Prader-Willi-like phenotype

Monosomy 1p36 is the most common subtelomeric microdeletion syndrome with an incidence rate estimated to be 1 in 5000 births. A hypothesis of a similarity between patients with 1p36 deletion and those with Prader-Willi syndrome and the existence of two different phenotypes for 1p36 microdeletion has been suggested. The main objective of the present study was to determine the existence of 1p36 microdeletion in a sample of patients with mental retardation, obesity and hyperphagia who tested negative by the methylation test for Prader-Willi syndrome. Sixteen patients (7 females, 9 males), 16-26 years old, were evaluated with high-resolution cytogenetic analysis at 550-850 band levels and with 11 polymorphic microsatellite markers located in the 1p36 region. All patients had normal cytogenetic and molecular results. The results obtained by high-resolution cytogenetic methodology were confirmed by the molecular analyses. We did not detect a 1p36 microdeletion in 16 subjects with the Prader-Willi-like phenotype, which reinforces that no correlation seems to exist between Prader-Willi-like phenotype and the 1p36 microdeletion syndrome.

Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

Background: To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD). Objective: To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS. Methods: The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed. Results: CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients. Conclusion: Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients.

Arterial Hypertension in a Child with Williams-Beuren Syndrome (7q11.23 Chromosomal Deletion)

We report the case of a 7-year-old male child diagnosed with Williams-Beuren syndrome and arterial hypertension refractory to clinical treatment. The diagnosis was confirmed by genetic study. Narrowing of the descending aorta and stenosis of the renal arteries were also diagnosed. Systemic vascular alterations caused by deletion of the elastin gene may occur early in individuals with Williams-Beuren syndrome, leading to the clinical manifestation of systemic arterial hypertension refractory to drug treatment.

Renal and urinary findings in 20 patients with Williams-Beuren syndrome diagnosed by fluorescence in situ hybridization (FISH)

PURPOSE: Williams-Beuren syndrome is a rare multiple anomalies/mental retardation syndrome caused by deletion of contiguous genes at chromosome region 7q11.23. The aim of this work was to determine the frequency and the types of renal and urinary tract anomalies in 20 patients with Williams-Beuren syndrome. METHODS: The fluorescence in situ hybridization test using a LSI Williams syndrome region DNA probe was performed for all 20 patients to confirm the diagnosis of Williams-Beuren syndrome. A prospective study was performed in order to investigate renal and urinary aspects using laboratory assays to check renal function, ultrasonography of the kidneys and urinary tract, voiding cystourethrogram and urodynamics. RESULTS: Deletion of the elastin gene (positive fluorescence in situ hybridization test) was found in 17 out of 20 patients. Renal alterations were diagnosed in 5 of 17 (29%) the patients with the deletion and in 1 of 3 patients without the deletion. Fourteen patients with the deletion presented dysfunctional voiding. Arterial hypertension was diagnosed in 3 patients with deletions and 1 of these presented bilateral stenosis of the renal arteries. CONCLUSIONS: Due to the high incidence of renal and urinary abnormalities in Williams-Beuren syndrome, performing a systematic laboratory and sonographic evaluation of the patients is recommended.

Williams-Beuren syndrome: cardiovascular abnormalities in 20 patients diagnosed with fluorescence in situ hybridization

OBJECTIVE: To evaluate the cardiovascular findings and clinical follow-up of patients with Williams-Beuren syndrome. METHODS: We studied 20 patients (11 males, mean age at diagnosis: 5.9 years old), assessed for cardiovascular abnormalities with electrocardiography and Doppler echocardiography. Fluorescence in situ hybridization (FISH) was used to confirm the diagnosis of the syndrome. RESULTS: Elastin gene locus microdeletion was detected in 17 patients (85%) (positive FISH), and in 3 patients deletion was not detected (negative FISH). Sixteen patients with a positive FISH (94%) had congenital cardiovascular disease (mean age at diagnosis: 2,3 years old). We observed isolated (2/16) supravalvular aortic stenosis and supravalvular aortic stenosis associated (11/16) with pulmonary artery stenosis (4/11); mitral valve prolapse (3/11); bicuspid aortic valve (3/11); aortic coarctation (2/11), thickened pulmonary valve (2/11); pulmonary valvular stenosis (1/11); supravalvular pulmonary stenosis (1/11); valvular aortic stenosis (1/11); fixed subaortic stenosis (1/11); pulmonary artery stenosis (2/16) associated with pulmonary valvar stenosis (1/2) and with mitral valve prolapse (1/2); and isolated mitral valve prolapse (1/16). Four patients with severe supravalvular aortic stenosis underwent surgery (mean age: 5.7 years old), and 2 patients had normal pressure gradients (mean follow-up: 8.4 years). CONCLUSION: A detailed cardiac evaluation must be performed in all patients with Williams-Beuren syndrome due to the high frequency of cardiovascular abnormalities.

Comparison of I-FISH and G-banding for the detection of chromosomal abnormalities during the evolution of myelodysplastic syndrome

Myelodysplastic syndrome (MDS) patients with a normal karyotype constitute a heterogeneous group from a biological standpoint and their outcome is often unpredictable. Interphase fluorescence in situ hybridization (I-FISH) studies could increase the rate of detection of abnormalities, but previous reports in the literature have been contradictory. We performed I-FISH and conventional karyotyping (G-banding) on 50 MDS patients at diagnosis, after 6 and 12 months or at any time if a transformation to acute myeloid leukemia (AML) was detected. Applying a probe-panel targeting the centromere of chromosomes 7 and 8, 5q31, 5p15.2 and 7q31, we observed one case with 5q deletion not identified by G-banding. I-FISH at 6 and 12 months confirmed the karyotype results. Eight cases transformed to AML during follow-up, but no hidden clone was detected by I-FISH in any of them. The inclusion of I-FISH during follow-up of MDS resulted in a small improvement in abnormality detection when compared with conventional G-banding.

Factorial validity of the Maslach Burnout Inventory (MBI-HSS) among Spanish professionals

OBJECTIVE: To assess the factorial validity and internal consistency of the Maslach Burnout Inventory (MBI-HSS). METHODS: In a sample consisting of 705 Spanish professionals from diverse occupational sectors (health, education, police and so one), seven plausible factorial models hypothesized were compared using LISREL 8. RESULTS: The four-factor oblique solution and the three-factor oblique solution showed the best and similar fit. Deletion of Item 12 and Item 16, taking into consideration the suggestions in the manual, improved the goodness of fit for both models. The four-factor oblique model suggests that, in addition to Emotional Exhaustion (EE) and Depersonalization (DP), Personal Accomplishment (PA) consists of two components labeled here Self-Competence (Items 4, 7, 17, and 21) and the Existential Component (Items 9, 12, 18, and 19). However, the alpha coefficient was relatively low for the Self-Competence component, suggesting that it is more suitable to estimate the syndrome as a threedimensional construct. The Cronbach's alpha was satisfactory for PA (alpha =.71) and EE (alpha =.85), and moderate for DP (alpha =.58). CONCLUSIONS: The results show that the MBI-HSS offers factorial validity and its scales present internal consistency to evaluate the quality of working life for Spanish professionals.

Risk factors for sudden infant death syndrome in a developing country

OBJECTIVE: To analyze whether previously identified risk factors for sudden death syndrome have a significant impact in a developing country. METHODS: Retrospective longitudinal case-control study carried out in Porto Alegre, Southern Brazil. Cases (N=39) were infants born between 1996 and 2000 who died suddenly and unexpectedly at home during sleep and were diagnosed with sudden death syndrome. Controls (N=117) were infants matched by age and sex who died in hospitals due to other conditions. Data were collected from postmortem examination records and questionnaires answers. A conditional logistic model was used to identify factors associated with the outcome. RESULTS: Mean age at death of cases was 3.2 months. The frequencies of infants regarding gestational age, breastfeeding and regular medical visits were similar in both groups. Sleeping position for most cases and controls was the lateral one. Supine sleeping position was found for few infants in both groups. Maternal variables, age below 20 years (OR=2, 95% CI: 1.1; 5.1) and smoking of more than 10 cigarettes per day during pregnancy (OR=3, 95% CI: 1.3; 6.4), significantly increased the risk for the syndrome. Socioeconomic characteristics were similar in both groups and did not affect risk. CONCLUSIONS: Infant-maternal and socioeconomic profiles of cases in a developing country closely resembled the profile described in the literature, and risk factors were similar as well. However, individual characteristics were identified as risks in the population studied, such as smoking during pregnancy and maternal age below 20 years.

Metabolic syndrome in fixed-shift workers

OBJECTIVE To analyze if metabolic syndrome and its altered components are associated with demographic, socioeconomic and behavioral factors in fixed-shift workers.METHODS A cross-sectional study was conducted on a sample of 902 shift workers of both sexes in a poultry processing plant in Southern Brazil in 2010. The diagnosis of metabolic syndrome was determined according to the recommendations from Harmonizing the Metabolic Syndrome. Its frequency was evaluated according to the demographic (sex, skin color, age and marital status), socioeconomic (educational level, income and work shift), and behavioral characteristics (smoking, alcohol intake, leisure time physical activity, number of meals and sleep duration) of the sample. The multivariate analysis followed a theoretical framework for identifying metabolic syndrome in fixed-shift workers.RESULTS The prevalence of metabolic syndrome in the sample was 9.3% (95%CI 7.4;11.2). The most frequently altered component was waist circumference (PR 48.4%; 95%CI 45.5;51.2), followed by high-density lipoprotein. Work shift was not associated with metabolic syndrome and its altered components. After adjustment, the prevalence of metabolic syndrome was positively associated with women (PR 2.16; 95%CI 1.28;3.64), workers aged over 40 years (PR 3.90; 95%CI 1.78;8.93) and those who reported sleeping five hours or less per day (PR 1.70; 95%CI 1.09;2.24). On the other hand, metabolic syndrome was inversely associated with educational level and having more than three meals per day (PR 0.43; 95%CI 0.26;0.73).CONCLUSIONS Being female, older and deprived of sleep are probable risk factors for metabolic syndrome, whereas higher educational level and higher number of meals per day are protective factors for metabolic syndrome in fixed-shift workers.

Use of medicines recommended for secondary prevention of acute coronary syndrome

ABSTRACT OBJECTIVE : To analyze if the demographic and socioeconomic variables, as well as percutaneous coronary intervention are associated with the use of medicines for secondary prevention of acute coronary syndrome. METHODS : In this cohort study, we included 138 patients with acute coronary syndrome, aged 30 years or more and of both sexes. The data were collected at the time of hospital discharge, and after six and twelve months. The outcome of the study was the simultaneous use of medicines recommended for secondary prevention of acute coronary syndrome: platelet antiaggregant, beta-blockers, statins and angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker. The independent variables were: sex, age, education in years of attending, monthly income in tertiles and percutaneous coronary intervention. We described the prevalence of use of each group of medicines with their 95% confidence intervals, as well as the simultaneous use of the four medicines, in all analyzed periods. In the crude analysis, we verified the outcome with the independent variables for each period through the Chi-square test. The adjusted analysis was carried out using Poisson Regression. RESULTS : More than a third of patients (36.2%; 95%CI 28.2;44.3) had the four medicines prescribed at the same time, at the moment of discharge. We did not observe any differences in the prevalence of use in comparison with the two follow-up periods. The most prescribed class of medicines during discharge was platelet antiaggregant (91.3%). In the crude analysis, the demographic and socioeconomic variables were not associated to the outcome in any of the three periods. CONCLUSIONS : The prevalence of simultaneous use of medicines at discharge and in the follow-ups pointed to the under-utilization of this therapy in clinical practice. Intervention strategies are needed to improve the quality of care given to patients that extend beyond the hospital discharge, a critical point of transition in care.

The importance to update the guidelines for the use of genetic testing in noncancer patients in Brazil

The Brazilian National Regulatory Agency for Private Health Insurance and Plans has recently published a technical note defining the criteria for the coverage of genetic testing to diagnose hereditary cancer. In this study we show the case of a patient with a breast lesion and an extensive history of cancer referred to a private service of genetic counseling. The patient met both criteria for hereditary breast and colorectal cancer syndrome screening. Her private insurance denied coverage for genetic testing because she lacks current or previous cancer diagnosis. After she appealed by lawsuit, the court was favorable and the test was performed using next-generation sequencing. A deletion of MLH1 exon 8 was found. We highlight the importance to offer genetic testing using multigene analysis for noncancer patients.

ERICA: prevalence of metabolic syndrome in Brazilian adolescents

ABSTRACT OBJECTIVE To determine the prevalence of metabolic syndrome and its components in Brazilian adolescents. METHODS We evaluated 37,504 adolescents who were participants in the Study of Cardiovascular Risks in Adolescents (ERICA), a cross-sectional, school-based, national study. The adolescents, aged from 12 to 17 years, lived in cities with populations greater than 100,000 inhabitants. The sample was stratified and clustered into schools and classes. The criteria set out by the International Diabetes Federation were used to define metabolic syndrome. Prevalences of metabolic syndrome were estimated according to sex, age group, school type and nutritional status. RESULTS Of the 37,504 adolescents who were evaluated: 50.2% were female; 54.3% were aged from 15 to 17 years, and 73.3% were from public schools. The prevalence of metabolic syndrome was 2.6% (95%CI 2.3-2.9), slightly higher in males and in those aged from 15 to 17 years in most macro-regions. The prevalence was the highest in residents from the South macro-region, in the younger female adolescents and in the older male adolescents. The prevalence was higher in public schools (2.8% [95%CI 2.4-3.2]), when compared with private schools (1.9% [95%CI 1.4-2.4]) and higher in obese adolescents when compared with nonobese ones. The most common combinations of components, referring to 3/4 of combinations, were: enlarged waist circumference (WC), low HDL-cholesterol (HDL-c) and high blood pressure; followed by enlarged WC, low HDL-c and high triglycerides; and enlarged WC, low HDL-c, high triglycerides and blood pressure. Low HDL was the second most frequent component, but the highest prevalence of metabolic syndrome (26.8%) was observed in the presence of high triglycerides. CONCLUSIONS ERICA is the first Brazilian nation-wide study to present the prevalence of metabolic syndrome and describe the role of its components. Despite the prevalence of Metabolic Syndrome being low, the high prevalences of some components and participation of others in the syndrome composition shows the importance of early diagnosis of this changes, even if not grouped within the metabolic syndrome.

Cryptosporidiosis among patients with acquired immunodeficiency syndrome (AIDS) in the county of São Paulo, Brazil

Stool samples of 157 patients with AIDS, living in the county of São Paulo, were submitted to several techniques in the search for Cryptosporidium sp.. Among the various techniques tested for slide preparation (direct smear, spontaneous sedimentation method, and formol-ether concentration), the latter, formol-ether concentration, offered the best results, clearly outdoing all the others. Nineteen samples out of 157 prepared by this technique, after dyeing by the Kinyoun method or by carbol fuchsin dimethyl sulfoxide, were found to be positive for Cryptosporidium sp..

Mediastinal and pulmonary entomophthoromycosis with superior vena cava syndrome: case report

The first case of mediastinal and pulmonary entomophthoromycosis with supe rior vena cava syndrome is reported. The patient presented with a history of edema of the face, neck and upper limbs as well as collateral circulation in the anterior wall of the chest. Histological examination of tissue from mediastinum revealed a granulomatous reaction with microabscesses surrounded by eosinophilic amorphous material and with broad hyphae in the center. Culture was not performed because a preliminary diagnosis of nonHodgkin's malignant lymphoma was made. Surgical correction of the obstructed area was performed and the patient was sucessfully treated with potassium iodide. The authors propose that mediastinal entomoph thoromycosis must be considered in the differential diagnosis of diseases causing superior vena cava syndrome in tropical and sub-tropical regions. This case enlarges the spectrum of clinical manifestations of the zigomycosis caused by Entomoph-thoraceae.

Aerosolised pentamidine for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome

The goal of this study was to evaluate inhaled pentamidine for the treatment of patients with mild and moderate Pneumocystis carinii pneumonitis. Eight adults with AIDS and pneumocystis pneumonia (4 with a first episode and 4 with a repeat pneumocystosis) received daily inhalations of aerosol pentamidine isethionate for 21 days. Six patients were treated with doses of 300 mg of pentamidine and the remaining 2 received 600 mg every day. In the 300 mg treatment group, 2 individuals showed discrete and transient neutropenia. However, both subjects that received 600 mg of aerosol pentamidine daily developed leukopenia. One of them had major toxicity (overall severe intolerance of 12.5%) that required drug discontinuation and did not allow any analysis of the treatment efficacy. Of the 7 evaluable patients, 6 (88%) completed the treatment successfuly. One subject of the 300 mg regimen experienced an early recurrence. In conclusion, inhaled pentamidine is an effective treatment for mild and moderate cases of P. carinii pneumonia. It is less toxic than standard anti-pneumocystis therapy and is suitable for outpatient use.