Volumetric Capnography For The Evaluation Of Chronic Airways Diseases.

Obstructive lung diseases of different etiologies present with progressive peripheral airway involvement. The peripheral airways, known as the silent lung zone, are not adequately evaluated with conventional function tests. The principle of gas washout has been used to detect pulmonary ventilation inhomogeneity and to estimate the location of the underlying disease process. Volumetric capnography (VC) analyzes the pattern of CO2 elimination as a function of expired volume. To measure normalized phase 3 slopes with VC in patients with non-cystic fibrosis bronchiectasis (NCB) and in bronchitic patients with chronic obstructive pulmonary disease (COPD) in order to compare the slopes obtained for the groups. NCB and severe COPD were enrolled sequentially from an outpatient clinic (Hospital of the State University of Campinas). A control group was established for the NCB group, paired by sex and age. All subjects performed spirometry, VC, and the 6-Minute Walk Test (6MWT). Two comparisons were made: NCB group versus its control group, and NCB group versus COPD group. The project was approved by the ethical committee of the institution. Statistical tests used were Wilcoxon or Student's t-test; P<0.05 was considered to be a statistically significant difference. Concerning the NCB group (N=20) versus the control group (N=20), significant differences were found in body mass index and in several functional variables (spirometric, VC, 6MWT) with worse results observed in the NCB group. In the comparison between the COPD group (N=20) versus the NCB group, although patients with COPD had worse spirometric and 6MWT values, the capnographic variables mean phase 2 slope (Slp2), mean phase 3 slope normalized by the mean expiratory volume, or mean phase 3 slope normalized by the end-tidal CO2 concentration were similar. These findings may indicate that the gas elimination curves are not sensitive enough to monitor the severity of structural abnormalities. The role of normalized phase 3 slope may be worth exploring as a more sensitive index of small airway disease, even though it may not be equally sensitive in discriminating the severity of the alterations.

Effect Of Roux-en-y Gastric Bypass On Nonalcoholic Fatty Liver Disease Evaluated Through Nafld Fibrosis Score: A Prospective Study.

Nonalcoholic fatty liver disease (NAFLD) is common among subjects who undergo bariatric surgery and its postsurgical improvement has been reported. This study aimed to determine the evolution of liver disease evaluated through NAFLD fibrosis score 12 months after surgery. It is a prospective cohort study which evaluated patients immediately before and 12 months following Roux-en-Y gastric bypass (RYGB). Mean score decreased from 1.142 to 0.066; surgery led to a resolution rate of advanced fibrosis of 55 %. Resolution was statistically associated with female gender, percentage of excess weight loss, postsurgical body mass index, postsurgical platelet count, and diabetes resolution. As previously reported by studies in which postsurgical biopsies were performed, RYGB leads to a great resolution rate of liver fibrosis. Since postsurgical biopsy is not widely available and has a significant risk, calculation of NAFLD fibrosis score is a simple tool to evaluate this evolution through a noninvasive approach.

Epiretinal Membrane Formation Associated With Idiopathic Macular Telangiectasia: Case Report.

A 46-year-old woman complained of blurred and distorted vision in both eyes. Ophthalmic examination showed that visual acuity was 20/200 for the right eye and counting fingers left eye. Fundoscopy revealed perimacular hemorrhages, aneurismal dilatation of the vessels in the posterior pole, and a white and elevated lesion adjacent to vascular changes. We report a case of idiopathic macular telangiectasia and epiretinal membrane that occurs concomitantly. To our knowledge, this is the first report that describes an association between idiopathic macular telangiectasia and epiretinal membrane formation.

Enhanced Endothelium-dependent Relaxation Of Rat Pulmonary Artery Following β-adrenergic Overstimulation: Involvement Of The No/cgmp/vasp Pathway.

The aim of this study was to investigate whether β-adrenoceptor (β-AR) overstimulation induced by in vivo treatment with isoproterenol (ISO) alters vascular reactivity and nitric oxide (NO) production and signaling in pulmonary arteries. Vehicle or ISO (0.3mgkg(-1)day(-1)) was administered daily to male Wistar rats. After 7days, the jugular vein was cannulated to assess right ventricular (RV) systolic pressure (SP) and end diastolic pressure (EDP). The extralobar pulmonary arteries were isolated to evaluate the relaxation responses, protein expression (Western blot), NO production (diaminofluorescein-2 fluorescence), and cyclic guanosine 3',5'-monophosphate (cGMP) levels (enzyme immunoassay kit). ISO treatment induced RV hypertrophy; however, no differences in RV-SP and EDP were observed. The pulmonary arteries from the ISO-treated group showed enhanced relaxation to acetylcholine that was abolished by the NO synthase (NOS) inhibitor N(ω)-nitro-l-arginine methyl ester (l-NAME); whereas relaxation elicited by sodium nitroprusside, ISO, metaproterenol, mirabegron, or KCl was not affected by ISO treatment. ISO-treated rats displayed enhanced endothelial NOS (eNOS) and vasodilator-stimulated phosphoprotein (VASP) expression in the pulmonary arteries, while phosphodiesterase-5 protein expression decreased. ISO treatment increased NO and cGMP levels and did not induce eNOS uncoupling. The present data indicate that β-AR overactivation enhances the endothelium-dependent relaxation of pulmonary arteries. This effect was linked to an increase in eNOS-derived NO production, cGMP formation and VASP content and to a decrease in phosphodiesterase-5 expression. Therefore, elevated NO bioactivity through cGMP/VASP signaling could represent a protective mechanism of β-AR overactivation on pulmonary circulation.

Nasal Potential Difference In Cystic Fibrosis Considering Severe Cftr Mutations.

The gold standard for diagnosing cystic fibrosis (CF) is a sweat chloride value above 60 mEq/L. However, this historical and important tool has limitations; other techniques should be studied, including the nasal potential difference (NPD) test. CFTR gene sequencing can identify CFTR mutations, but this method is time-consuming and too expensive to be used in all CF centers. The present study compared CF patients with two classes I-III CFTR mutations (10 patients) (G1), CF patients with classes IV-VI CFTR mutations (five patients) (G2), and 21 healthy subjects (G3). The CF patients and healthy subjects also underwent the NPD test. A statistical analysis was performed using the Mann-Whitney, Kruskal-Wallis, χ(2), and Fisher's exact tests, α = 0.05. No differences were observed between the CF patients and healthy controls for the PDMax, Δamiloride, and Δchloride + free + amiloride markers from the NPD test. For the finger value, a difference between G2 and G3 was described. The Wilschanski index values were different between G1 and G3. In conclusion, our data showed that NPD is useful for CF diagnosis when classes I-III CFTR mutations are screened. However, if classes IV-VI are considered, the NPD test showed an overlap in values with healthy subjects.

[factors Impacting The Growth And Nutritional Status Of Cystic Fibrosis Patients Younger Than 10 Years Of Age Who Did Not Undergo Neonatal Screening.]

The aim of this study was to evaluate by clinical and laboratory parameters how cystic fibrosis (CF) affects growth and nutritional status of children who were undergoing CF treatment but did not receive newborn screening. A historical cohort study of 52 CF patients younger than 10 years of age were followed in a reference center in Campinas, Southeast Brazil. Anthropometric measurements were abstracted from medical records until March/2010, when neonatal screening program was implemented. Between September/2009 and March/2010, parental height of the 52 CF patients were also measured. Regarding nutritional status, four patients had Z-scores ≤ -2 for height/age (H/A) and body mass index/age (BMI/A). The following variables were associated with improved H/A ratio: fewer hospitalizations, longer time from first appointment to diagnosis, longer time from birth to diagnosis and later onset of respiratory disease. Forced vital capacity [FVC(%)], forced expiratory flow between 25-75% of FVC [FEF25-75(%)], forced expiratory volume in the first second [FEV1(%)], gestational age, birth weight and early respiratory symptoms were associated with IMC/A. Greater number of hospitalizations, diagnosis delay and early onset of respiratory disease had a negative impact on growth. Lower spirometric values, lower gestational age, lower birth weight, and early onset of respiratory symptoms had negative impact on nutritional status. Malnutrition was observed in 7.7% of cases, but 23% of children had nutritional risk.

Hormônio de crescimento em crianças e adolescentes com fibrose cística

The recombinant human growth hormone (rhGH) can improve weight gain, physical growth, clinical and lung in cystic fibrosis (CF). However, the routine use, although promising, is not established in the literature. The objective of this study was to assess the benefits of rhGH in children and adolescents with CF. We conducted a systematic review in the database PubMed, Lilacs, SciELO and Cochrane, in the period 2000-2010, using the keywords: cystic fibrosis, growth hormone, children and adolescents. We found 77 articles and included 11 randomized controlled trials, with 290 children and adolescents with CF. The short-term use (1-24 months) of rhGH improved the height, weight, growth rate, bone mineral content and components of pulmonary function. Adverse effects, like diabetes, were not observed in the studies. The short-term use of rhGH improved growth and body composition in patients with CF.

Juvenile idiopathic arthritis with involvement of the temporomandibular joint: the role of image examinations

PURPOSE: Juvenile idiopathic arthritis (JIA) has unknown etiology, and the involvement of the temporomandibular joint (TMJ) is rare in the early phase of the disease. The present article describes the use of computed tomography (CT) and magnetic resonance (MRI) images for the diagnosis of affected TMJ in JIA. CASE DESCRIPTION: A 12-year-old, female, Caucasian patient, with systemic rheumathoid arthritis and involvement of multiple joints was referred to the Imaging Center for TMJ assessment. The patient reported TMJ pain and limited opening of the mouth. The helical CT examination of the TMJ region showed asymmetric mandibular condyles, erosion of the right condyle and osteophyte-like formation. The MRI examination showed erosion of the right mandibular condyle, osteophytes, displacement without reduction and disruption of the articular disc. CONCLUSION: The disorders of the TMJ as a consequence of JIA must be carefully assessed by modern imaging methods such as CT and MRI. CT is very useful for the evaluation of discrete bone changes, which are not identified by conventional radiographs in the early phase of JIA. MRI allows the evaluation of soft tissues, the identification of acute articular inflammation and the differentiation between pannus and synovial hypertrophy.

Microlithiasis of the gallbladder: role of endoscopic ultrasonography in patients with idiopathic acute pancreatitis

OBJECTIVES: Causes may be found in most cases of acute pancreatitis, however no etiology is found by clinical, biological and imaging investigations in 30% of these cases. Our objective was to evaluate results from endoscopic ultrasonography (EUS) for diagnosis of gallbladder microlithiasis in patients with unexplained (idiopathic) acute pancreatitis. METHODS: Thirty-six consecutive non-alcoholic patients with diagnoses of acute pancreatitis were studied over a five-year period. None of them showed signs of gallstones on transabdominal ultrasound or tomography. We performed EUS within one week of diagnosing acute pancreatitis. Diagnosis of gallbladder microlithiasis on EUS was based upon findings of hyperechoic signals of 0.5-3.0 mm, with or without acoustic shadowing. All patients (36 cases) underwent cholecystectomy, in accordance with indication from the attending physician or based upon EUS diagnosis. RESULTS: Twenty-seven patients (75%) had microlithiasis confirmed by histology and nine did not (25%). EUS findings were positive in twenty-five. Two patients had acute cholecystitis diagnosed at EUS that was confirmed by surgical and histological findings. In two patients, EUS showed cholesterolosis and pathological analysis disclosed stones not detected by EUS. EUS diagnosed microlithiasis in four cases not confirmed by surgical treatment. In our study, sensitivity, specificity and positive and negative predictive values to identify gallbladder microlithiasis (with 95% confidence interval) were 92.6% (74.2-98.7%), 55.6% (22.7-84.7%), 86.2% (67.4-95.5%) and 71.4% (30.3-94.9%), respectively. Overall EUS accuracy was 83.2%. CONCLUSIONS: EUS is a very reliable procedure to diagnose gallbladder microlithiasis and should be used for the management of patients with unexplained acute pancreatitis. This procedure should be part of advanced endoscopic evaluation.

Oxigenoterapia domiciliar prolongada em crianças e adolescentes: uma análise do uso clínico e de custos de um programa assistencial

OBJETIVOS: Descrever as características clínicas e laboratoriais dos pacientes em oxigenoterapia domiciliar prolongada acompanhados pelo programa de atendimento domiciliar do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, durante um período de 8 anos, e comparar os grupos com e sem hipertensão pulmonar secundária. Estimar o custo do programa utilizando concentradores versus cilindros de oxigênio arcados pela instituição. MÉTODOS: Estudo descritivo retrospectivo e de coorte dos pacientes em oxigenoterapia domiciliar prolongada, em seguimento no período de 2002 a 2009, na Unidade de Pneumologia do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTADOS: Foram estudados 165 pacientes, 53% do sexo masculino, com as medianas: idade de início da oxigenoterapia - 3,6 anos; tempo de oxigenoterapia - 7 anos; e tempo de sobrevida após início da oxigenoterapia - 3,4 anos. Os principais diagnósticos foram: fibrose cística (22%), displasia broncopulmonar (19%) e bronquiolite obliterante (15%). Dos 33 pacientes que realizaram espirometria, 70% apresentavam distúrbio ventilatório obstrutivo grave. O exame ecocardiográfico foi executado em 134 pacientes; 51% deles tinham hipertensão pulmonar secundária. Houve associação estatisticamente significante entre: presença de hipertensão pulmonar e necessidade de maiores fluxos de oxigênio (qui-quadrado, p = 0,011); e presença de hipertensão pulmonar e maior tempo de oxigenoterapia (Logrank, p = 0,0001). Não houve diferença estatisticamente significante entre tempo de sobrevida após início da oxigenoterapia e presença de hipertensão pulmonar. Os custos médios mensais do programa foram: US$ 7.392,93 para os concentradores e US$ 16.630,92 para cilindros. CONCLUSÕES: A oxigenoterapia domiciliar prolongada foi empregada em distintas doenças crônicas, predominantemente em lactentes e pré-escolares. Houve alta frequência de hipertensão pulmonar associada a maiores períodos de uso e fluxos de oxigênio, sem associação à sobrevida. A substituição dos cilindros por concentradores poderá reduzir custos significativamente.

Shwachman-Kulczycki score still useful to monitor cystic fibrosis severity

INTRODUCTION: The Shwachman-Kulczycki score was the first scoring system used in cystic fibrosis to assess disease severity. Despite its subjectivity, it is still widely used. OBJECTIVE: To study correlations among forced expiratory volume in one second (FEV1), chest radiography, chest computed tomography, 6-minute walk test, and Shwachman-Kulczycki score in patients with cystic fibrosis and to test whether the Shwachman-Kulczycki score is still useful in monitoring the severity of the disease. METHODS: A cross-sectional prospective study was performed to analyze the correlations (Spearman). Patients with clinically stable cystic fibrosis, aged 3-21 years, were included. RESULTS: 43 patients, 19F/24M, mean age 10.5 + 4.7 years, with a median Shwachman-Kulczycki score of 70 were studied. The median Brasfield and Bhalla scores were 17 and 10, respectively. The mean Z score for the 6-minute walk test was -1.1 + 1.106 and the mean FEV1 was 59 + 26 (as percentage of predicted values). The following significant correlations versus the Shwachman-Kulczycki score were found: FEV1 (r = 0.76), 6-minute walk test (r = 0.71), chest radiography (r = 0.71) and chest computed tomography (r = -0.78). When patients were divided according to FEV1, a statistically significantly correlation with the Shwachman-Kulczycki score was found only in patients with FEV1 <70% (r = 0.67). CONCLUSIONS: The Shwachman-Kulczycki score remains an useful tool for monitoring the severity of cystic fibrosis, adequately reflecting the functional impairment and chest radiography and tomography changes, especially in patients with greater impairment of lung function. When assessing patients with mild lung disease its limitations should be considered and its usefulness in such patients should be evaluated in larger populations.

Hepatotrophic factors reduce hepatic fibrosis in rats

CONTEXT: Hepatic fibrosis occurs in response to several aggressive agents and is a predisposing factor in cirrhosis. Hepatotrophic factors were shown to stimulate liver growth and to restore the histological architecture of the liver. They also cause an improvement in liver function and accelerate the reversion of fibrosis before it progresses to cirrhosis. OBJECTIVE: To test the effects of hepatic fibrosis solution composed by amino acids, vitamins, glucose, insulin, glucagon and triiodothyronine on hepatic fibrosis in rats. METHODS: Fibrosis was induced in rats by gastric administration of dimethylnitrosamine (10 mg/kg) for 5 weeks. After liver biopsy, the rats received either hepatotrophic factors solution (40 mg/kg/day) or saline solution for 10 days by intraperitoneal injection. Blood samples and liver fragments were collected for hepatic function analysis, standard histopathology evaluation, and morphometric collagen quantification. RESULTS: Rats in the hepatotrophic factors group showed a decrease of the histopathological components of fibrosis and an increase of their hepatic mass (12.2%). There was no development of neoplasic lesions in both groups. Compared with the saline group, the hepatotrophic factors group also had a decrease of blood levels of hepatic-lesion markers (AST, ALT) and a decrease of collagen content in the portal spaces (31.6%) and perisinusoidal spaces (42.3%), as well as around the hepatic terminal vein (57.7%). Thus, hepatotrophic factors administration in the portal blood promoted a regenerative hepatic response, with an overall reduction of the volumetric density of collagen, improved hepatic function, and a general improvement in the histopathological aspects of fibrosis. CONCLUSION: Taken together, these results suggest the potential therapeutic use of this hepatotrophic factors solution to treat chronic liver diseases.

Expression and distribution of connexin 32 in rat liver with experimentally induced fibrosis

The connexin 32 (Cx32) is a protein that forms the channels that promote the gap junction intercellular communication (GJIC) in the liver, allowing the diffusion of small molecules through cytosol from cell-to-cell. Hepatic fibrosis is characterized by a disruption of normal tissue architeture by cellular lesions, and may alter the GJIC. This work aimed to study the expression and distribution of Cx32 in liver fibrosis induced by the oral administration of dimethylnitrosamine in female Wistar rats. The necropsy of the rats was carried out after five weeks of drug administration. They presented a hepatic fibrosis state. Sections from livers with fibrosis and from control livers were submitted to immunohistochemical, Real Time-PCR and Western-Blot analysis to Cx32. In fibrotic livers the Cxs were diffusely scattered in the cytoplasm, contrasting with the control livers, where the Cx32 formed junction plaques at the cell membrane. Also it was found a decrease in the gene expression of Cx32 without reduction in the protein quantity when compared with controls. These results suggest that there the mechanism of intercellular communication between hepatocytes was reduced by the fibrotic process, which may predispose to the occurrence of a neoplastic process, taken in account that connexins are considered tumor suppressing genes.

Aerobic capacity and skeletal muscle function in children with asthma

Background Peripheral muscle strength and endurance are decreased in patients with chronic pulmonary diseases and seem to contribute to patients' exercise intolerance. However, the authors are not aware of any studies evaluating peripheral muscle function in children with asthma. It seems to be implied that children with asthma have lower aerobic fitness, but there are limited studies comparing the aerobic capacity of children with and without asthma. The present study aimed to evaluate muscle strength and endurance in children with persistent asthma and their association with aerobic capacity and inhaled corticosteroid consumption. Methods Forty children with mild persistent asthma (MPA) or severe persistent asthma (SPA) (N=20 each) and 20 children without asthma (control group) were evaluated. Upper (pectoralis and latissimus dorsi) and lower (quadriceps) muscle strength and endurance were assessed, and cardiopulmonary exercise testing was performed. Inhaled corticosteroid consumption during the last 6 and 24 months was also quantified. Results Children with SPA presented a reduction in peak oxygen consumption (VO(2)) (28.2 +/- 8.1 vs 34.7 +/- 6.9 ml/kg/min; p<0.01) and quadriceps endurance (43.1 +/- 6.7 vs 80.9 +/- 11.9 repetitions; p<0.05) compared with the control group, but not the MPA group (31.5 +/- 6.1 ml/kg/min and 56.7 +/- 47.7 repetitions respectively; p>0.05). Maximal upper and lower muscle strength was preserved in children with both mild and severe asthma (p>0.05). Finally, the authors observed that lower muscle endurance weakness was not associated with reductions in either peak VO(2) (r=0.22, p>0.05) or corticosteroid consumption (r=-0.31, p>0.05) in children with asthma. Conclusion The findings suggest that cardiopulmonary exercise and lower limb muscle endurance should be a priority during physical training programs for children with severe asthma.

Cardiomyopathy, adult valve disease and heart failure in South America

Continued assessment of temporal trends in mortality and epidemiology of specific cardiovascular diseases in South America is needed to provide a scientific basis for rational allocation of the limited healthcare resources and introduction of strategies to reduce risk and predict the future burden of cardiovascular disease. The epidemiology of cardiomyopathies, adult valve disease and heart failure (HF) in South America is reviewed here. Diseases of the circulatory system are the main cause of death based on data from about 50% of the South American population. Among the cardiovascular causes of death, cerebrovascular disease is predominant followed by ischaemic heart disease, other heart diseases and hypertensive disease. Of note, cerebrovascular disease is the main cause of death in women, and race also influenced cardiovascular mortality rates. HF is the most important cardiovascular reason for admission to hospital due to cardiovascular disease of ischaemic, idiopathic dilated cardiomyopathic, valvular, hypertensive and chagasic aetiologies. Also, mortality due to HF is high, especially owing to Chagas' disease. HF and aetiologies associated with HF are responsible for 6.3% of deaths. Rheumatic fever is the leading cause of valvular heart disease. The findings have important public health implications because the allocation of healthcare resources, and strategies to reduce the risk of HF should also consider controlling Chagas' disease and rheumatic fever in South American countries.