Eisenmenger syndrome in the adult--experience with new drugs for the treatment of pulmonary hypertension.

BACKGROUND: The last few years have seen significant progress in the treatment of advanced pulmonary arterial hypertension (PAH). The efficacy of new drugs has been proved mainly in idiopathic PAH or PAH associated with connective tissue diseases. As the pathophysiologic patterns are similar, it is reasonable to use these drugs also in Eisenmenger syndrome or in other congenital heart defects with PAH related to initial high pulmonary flow. OBJECTIVES: To evaluate our early experience with new drugs for PAH in patients with Eisenmenger syndrome. METHODS: A retrospective study of five patients, aged 28 to 51 years (39.6 +/- 9.94), four female, with Eisenmenger syndrome due to atrial septal defect (n = 2), patent ductus arteriosus (n = 2) or ventricular septal defect (n = 1), who began therapy with iloprost (n = 4, later associated with sildenafil in one patient) and bosentan (n = 1), between April 2001 and May 2003. The existence of severe and fixed PAH, with predominant right-to-left shunt, was confirmed by hemodynamic study in all cases. The patients were evaluated by clinical examination, Doppler echocardiography and the six-minute walk test before treatment and throughout follow-up (9 to 34 months, 19.8 +/- 9.04). Before treatment two patients were in NYHA class III and three in class III with periods in class IV. By Doppler echocardiography the right ventricle-right atrium (RV-RA) gradient was 74 to 111 mmHg (90.6 +/- 15.73) and the Tei index was 0.53 to 2.05 (1.13 +/- 0.62). In the six-minute walk test the distance was 214 to 500 meters (296.8 +/- 115.27). RESULTS: All patients improved clinically, though three are still in class III. One patient is in class II and one patient died. At the latest evaluation the RV-RA gradient was 60 to 112 mmHg (84.8 +/- 19.11) and the Tei index was 0.5 to 1.33 (0.85 +/- 80.32). In the six-minute walk test a net increase in the distance covered was evident: 376 to 520 meters (420 +/- 57.89). The treatment was well tolerated in all cases, without serious adverse effects. CONCLUSIONS: Though the number of patients was small, our initial experience with the new specific drugs for PAH in Eisenmenger syndrome showed promising results, with clinical and functional improvement and without adverse effects.     

Usefulness of the ECG in the sports screening of footballers affiliated to a regional sports federation

We report the results of a study carried out in 825 young football club members, all of whom underwent screening for hypertrophic cardiomyopathy using a 12-lead ECG. Echocardiographic assessment was performed in only those with positive ECG results, as defined by the European Society of Cardiology. Echocardiography proved necessary in 61 (7%) individuals with positive ECG findings, of whom 7 had echocardiographic findings indicative of left ventricular hypertrophy: five were in the "gray zone", 1 was judged to have athlete's heart, and one had been diagnosed with hypertrophic cardiomyopathy. In all these cases, ECG showed repolarization abnormalities, and 4 satisfied criteria for left ventricular hypertrophy.     

Genetic diversity, population structure and drug resistance of Mycobacterium tuberculosis in Peru

This paper presents the first evaluation of the molecular epidemiology of Mycobacterium tuberculosis in Peru. We characterised 323 isolates using spoligotyping and mycobacterial interspersed repetitive units variable number tandem repeats (MIRU-VNTR) typing. We aimed to determine the levels of genetic diversity and genetic differentiation among and within Peruvian isolates and the epidemiological factors which may be driving patterns of population structure and evolution of M. tuberculosis in Peru. Our results compared to the fourth international spoligotyping database (SpolDB4) and MIRU-VNTRplus, show that the main M. tuberculosis families present are Latin American-Mediterranean, Haarlem, T, and Beijing. Bayesian clustering recovered 15 groups in the Peruvian M. tuberculosis isolates, among which two were composed mainly of orphans, implying the presence of native "Peruvian" strains not previously reported. Variable levels of association with drug resistance were observed, with Beijing genotypes not showing any association with multidrug resistance, while in other groups MIRU-VNTR loci 2, 23, 31, and 40 were found to be associated with the multidrug-resistant tuberculosis (MDR-TB) phenotype, suggesting that a linkage disequibrium between these MIRU and drug resistance loci may be present. Genetic differentiation was present among drug resistant and sensitive strains. Ethambutol appeared to be the main driver of differentiation, suggesting that strong selection pressure could have been exerted by drug treatment in Peru over recent years.     

A clinical prediction rule for pulmonary tuberculosis in emergency departments.

SETTING: University-affiliated hospital located in an area with a high incidence of pulmonary tuberculosis (PTB). OBJECTIVE: To develop a clinical prediction rule (CPR) based on information obtainable on admission, to permit rapid identification of patients with PTB. DESIGN: Information from patients with respiratory symptoms who attended the emergency department of Cayetano Heredia Hospital, Lima, Peru, was collected prospectively. Clinical symptoms, past medical history, demographic data and results of chest X-rays (CXRs), sputum smear and culture in L?wenstein-Jensen media were obtained. Based on logistic regression, we constructed a scoring system to predict PTB. RESULTS: A total of 345 patients were enrolled in the study, including 109 (31%) culture-proven PTB cases. In logistic regression analysis, we found age, previous history of PTB, weight loss, presence of cavities, upper lobe infiltrate and miliary pattern on CXR as independent predictors of PTB. We designed a scoring system with these variables, taking into account their statistical weight. The score attained 93% sensitivity and 42% specificity. CONCLUSION: The CPR that was developed performed well in our population. It merits further validation in other settings. It should not, however, replace, but should complement sputum microscopy when deciding on isolation, and it does not preclude microbiology in making a definitive diagnosis.     

Yield of fluorescence microscopy versus culture for tuberculosis at a middle-income country referral hospital

The aim of this study was to determine the usefulness of fluorescence microscopy (FM) at a referral centre in a middle-income country. Direct Ziehl-Neelsen (ZN) and direct, as well as concentrated, smear FM were performed on 2179 suspect sputa, with L?wenstein-Jensen (LJ) culture as the gold standard. ZN, direct FM and concentration FM detected 36.0, 38.6 and 37.0%, respectively, of 272 culture-positive specimens. Patient-wise, there were 8.1% (126/1553) positives on any smear compared with 12.0% (187/1553) on any culture. ZN, direct FM and concentrated FM smear were positive in 43.3, 46.5 and 45.5%, respectively, of culture-proven cases. All differences between microscopy and culture were significant (P<0.001), but not those between microscopy techniques. Acid-fast bacilli (AFB) were not rare in 60% of 48 duplicate smears, positive in ZN or FM only. Simple LJ culture, but not FM on direct or concentrated smears, was thus significantly more sensitive than ZN smears. The considerable numbers of AFB found in positive direct smears from discordant microscopy sets suggest that repeating smears can improve microscopy sensitivity more than variations of correctly executed technique, provided that overload is avoided. Thus FM could be particularly useful, as it is time-saving and could protect against the sensitivity loss associated with high workload.     

Florid cemento-osseous dysplasia: a report of three cases

Florid cemento-osseous dysplasia (FCOD) is a non-neoplastic condition of the jaws that is not associated with inflammation of the pulp or periodontal tissue. This article reports on three cases that were diagnosed as FCOD, demonstrating the importance of both clinical and radiographic diagnosis and the clinical management of these lesions.     

Chemoreception in the context of the general biology of ROS

Superoxide anion is the most important reactive oxygen species (ROS) primarily generated in cells. The main cellular constituents with capabilities to generate superoxide anion are NADPH oxidases and mitochondrial respiratory chain. The emphasis of our article is centered in critically examining hypotheses proposing that ROS generated by NADPH oxidase and mitochondria are key elements in O(2)-sensing and hypoxic responses generation in carotid body chemoreceptor cells. Available data indicate that chemoreceptor cells express a specific isoform of NADPH oxidase that is activated by hypoxia; generated ROS acting as negative modulators of the carotid body (CB) hypoxic responses. Literature is also consistent in supporting that poisoned respiratory chain can produce high amounts of ROS, making mitochondrial ROS potential triggers-modulators of the CB activation elicited by mitochondrial venoms. However, most data favour the notion that levels of hypoxia, capable of strongly activating chemoreceptor cells, would not increase the rate of ROS production in mitochondria, making mitochondrial ROS unlikely triggers of hypoxic responses in the CB. Finally, we review recent literature on heme oxygenases from two perspectives, as potential O(2)-sensors in chemoreceptor cells and as generators of bilirubin which is considered to be a ROS scavenger of major quantitative importance in mammalian cells.