One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease

Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17) was prospectively followed for 0.7 to 4.0 years (median 3.6 years). Plasma levels of von Willebrand factor antigen (VWF:Ag), tissue plasminogen activator (t-PA) and its inhibitor (PAI-1), P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106% increase, P < 0.003). Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response). Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6) correlated with disease severity indices (P < 0.05). Seven patients died during follow-up. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was independently associated with a high risk of death (hazard ratio = 6.56, 95%CI = 1.46 to 29.4, P = 0.014). Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival.

Histidine-tryptophan-ketoglutarate solution decreases mortality and morbidity in high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease: an 11-year experience from a single institution

Cardioplegic reperfusion during a long term ischemic period interrupts cardiac surgery and also increases cellular edema due to repeated solution administration. We reviewed the clinical experiences on myocardial protection of a single perfusion with histidine-tryptophan-ketoglutarate (HTK) for high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease. This retrospective study included 101 high-risk patients undergoing arterial switch operation between March 2001 and July 2012. We divided the cohort into two groups: HTK group, myocardial protection was carried out with one single perfusion with HTK solution; and St group, myocardial protection with conventional St. Thomas' crystalloid cardioplegic solution. The duration of cardiopulmonary bypass did not differ between the two groups. The mortality, morbidity, ICU stay, post-operative hospitalization time, and number of transfusions in HTK group were lower than those in St group (P<0.05). Univariate and multivariate analysis showed that HTK is a statistically significant independent predictor of decreased early mortality and morbidity (P<0.05). In conclusion, HTK solution seems to be an effective and safe alternative to St. Thomas' solution for cardioplegic reperfusion in high-risk patients with complex congenital heart disease.

Acute myocardial infarction in chronic Chagas' cardiomyopathy: report of two cases with no obstructive coronary artery lesions

This report describes two patients with chronic Chagas' Heart Disease who developed clinical and laboratorial signs of myocardial infarction. Both patients presented sudden oppressive chest pain, without precipitating factor. In the first case, the highest MB-CK value was 65 IU, 22 hours after the beginning of the pain. On the second case, it was 77 IU at 18 hours after the beginning of the pain. In both cases ECG changes suggesting non-transmural infarction were present. The 99mTc PYP myocardial scintigram of the first case was positive. Coronary angiograms performed on the 18th and 9th day, respectively, after the acute infarction did not display obstructive lesions. Possible mechanisms causing myocardial infarction with normal coronary arteries in Chagas' Disease may include: embolic event's, particularly when there is associated congestive heart failure; coronary thrombosis and coronary spasms.

Pulmonary cavities colonized by actinomycetes: report of six cases

Six cases of a cavitary pulmonary ball formed by Actinomycetes are reported. They were observed in the state of Bahia, Brazil. All patients complained of cough and hemoptysis and the pathological study showed bronchiectasis and small cavities in the lungs. The lesions contained micro-colonies of Actinomyces, identified by morphology, staining properties and culture in two cases (thioglycolate media). In the six patients the disease was limited to the lungs. In one patient grains were found, within micro-abscesses in the surrounding parenchyma. Probably the invasion occurred due to ulceration of bronchial mucosa that was covered by granulation tissue. The author suggests that as in nocardiosis actinomycosys may have an invasive form, a saprophytic one may and colonize pulmonary cavities.

Pulmonary manifestations in the initial phase of schistosomiasis mansoni

The clinical and radiological pulmonary manifestations in the initial phase of schistosomiasis mansoni were studied in thirty previously healthy individuals who were simultaneously infected. The findings were compared with those concerning a control group and related to possible pathogenetic factors. The respiratory manifestations were of light or of moderate intensity, the dry cough being the most common symptom. The significant radiological alterations were: thickening of bronchial walls and beaded micronodulation, predominantly localized in the lower pulmonary fields. It was observed significant association between wheezing and IgE levels, estimated by the area of immediate intradermal reaction, as well as between the number of blood eosinophils and the occurrence of radiological changes. Moreover, there was correlation between the worm burden and the presence of wheezing, thoracic pain and beaded micronodulation. Thus, the clinical and radiological pulmonary manifestations described are significant part of the initial phase of schistosomiasis mansoni and present the worm burden, eosinophilia and levels of IgE as probable pathogenetic factors.

Mycobacterium avium complex (MAC) isolated from AIDS patients and the criteria required for its implication in disease

Before the AIDS pandemia, the Mycobacterium avium complex (MAC) was responsible in most cases for the pneumopathies that attack patients with basic chronic pulmonary diseases such as emphysema and chronic bronchitis36. In 1981, with the advent of the acquired immunodeficiency syndrome (AIDS), MAC started to represent one of the most frequent bacterial diseases among AIDS patients, with the disseminated form of the disease being the major clinical manifestation of the infection8. Between January 1989 and February 1991, the Section of Mycobacteria of the Adolfo Lutz Institute, São Paulo, isolated MAC from 103 patients by culturing different sterile and no-sterile processed specimens collected from 2304 patients seen at the AIDS Reference and Training Center and/or Emilio Ribas Infectology Institute. Disseminated disease was diagnosed in 29 of those patients on the basis of MAC isolation from blood and/or bone marrow aspirate. The other 74 patients were divided into categories highly (5), moderately (26) and little suggestive of disease (43) according to the criteria of DAVIDSON (1989)10. The various criteria for MAC isolation from sterile and non-sterile specimens are discussed.

Human pulmonary dirofilariasis: a review

The authors presented a detailed summary of the geographical distribution, clinical and pathological aspects of human pulmonary dirofilariasis. Although benign, this zoonosis, of which Dirofilaria immitis is the major etiological agent, represents a medical problem since it produces symptoms which may be confused with neoplasia and thus may subject patients to unnecessary thoracic surgery. Of 229 cases cited in the literature, only 17 were reported in Brazil, despite the existence of highly favorable conditions for the transmission of this infection in man. Thus it may well be that this parasitic infection remains underdiagnosed. Finally, the importance of a differential diagnosis between dirofilariasis and pulmonary neoplasia is emphasized in cases where there is a solitary subpleural nodule ("coin lesion") present. In addition, the development and improvement of modern immunological diagnostic techniques are essential to distinguish this benign disease from other pathological conditions and thus avoid unneccessary surgery. These techniques may reveal the true prevalence of this parasitic infection in our environment.

Hantavirus Pulmonary Syndrome: Report of the first three cases in São Paulo, Brazil

The hantavirus pulmonary syndrome was first recognized in cases that occurred in the U.S. in 1993, which served as an alert not only for American physicians but also for physicians in other countries for the identification of the disease. In the city of São Paulo, Brazil, 3 cases of the syndrome were recorded in 1993. The patients were young brothers residing in the Mata Atlântica (Atlantic Forest) region submitted to recent deforestation. Two of the patients died of acute respiratory insufficiency and the third recovered without sequelae. In the surviving patient the diagnosis was established by a laboratory criterion based on the detection of specific IgM and IgG class antibodies by indirect immunofluorescence. In the two patients who died, the diagnosis was confirmed by laboratory tests using immunoperoxidase technique for hantavirus in tissue, in histological lung and heart sections in one case, and by clinical and epidemiological data in the other

Hantavirus pulmonary syndrome in Anajatuba, Maranhão, Brazil

The authors report a confirmed case of hantavirus pulmonary syndrome in the rural area of the municipality of Anajatuba, state of Maranhão. Two other suspected cases from the same region are also described. The confirmed case involved a previously healthy young woman who died with signs and symptoms of acute respiratory insufficiency 5 days after presenting fever, myalgia and a dry cough. The patient was a student who was helping her parents with work in the fields; it was a habit of the family to store rice inside the house. The suspected cases involved two first-degree relatives working as field hands who died of acute respiratory insufficiency 24 and 48 hours, respectively, after presenting fever, myalgia and a dry cough. Both stored rice and corn inside their home. People living in the region reported massive infestations with rats in the woods and fields.

A retrospective evaluation of a score system adopted by the Ministry of Health, Brazil in the diagnosis of pulmonary tuberculosis in childhood: a case control study

Based on a retrospective case-control study we evaluated the score system adopted by the Ministry of Health of Brazil (Ministério da Saúde - MS), to diagnose pulmonary tuberculosis (PTB) in childhood. This system is independent of bacteriological or histopathological data to define a very likely (> or = 40 points), possible (30-35 points) or unlikely (< or = 25 points) diagnosis of tuberculosis. Records of hospitalized non-infected HIV children at the Instituto de Puericultura e Pediatria Martagão Gesteira of Federal University of Rio de Janeiro (IPPMG-UFRJ), were reviewed. Patients were adjusted for age and divided in two different groups: 45 subjects in the case group (culture-positive) [mean of age = 10.64 mo; SD 9.66]; and 96 in the control group (culture-negative and clinic criteria that dismissed the disease) [mean of age = 11.79 mo.; SD 11.31]. Among the variables analyzed, the radiological status had the greater impact into the diagnosis (OR = 25.39), followed by exposure to adult with tuberculosis (OR = 10.67), tuberculin skin test >10mm (OR = 8.23). The best cut-off point to the diagnosis of PTB was 30 points, where the score system was more accurate, with sensitivity of 88.9% and specificity of 86.5%.

Pulmonary tuberculosis: relationship between sputum bacilloscopy and radiological lesions

OBJECTIVES: To determine the frequency of radiological manifestations of chest tuberculosis among the tuberculosis outpatients at the Santa Casa de Misericórdia de São Paulo Hospital, and to correlate these radiological findings with the sputum bacilloscopy. SAMPLE AND METHODS: A review was made of the medical record cards and chest X-rays of all patients attended between January 1996 and December 1998. Patients with a diagnosis of tuberculosis who presented intrathoracic manifestations of the disease and negative anti-HIV serology were selected. RESULTS: The selection included 153 patients, with an average age of 37.5 years, who were predominantly male (60.8%) and white (56.9%). Pulmonary lesions were present in 121 (79.9%) and extrapulmonary lesions in 32 (20.1%). Parenchymal-infiltrate lesions appeared in 56 patients (36.6%), cavity lesions in 55 (36.0%), pleural effusion in 28 (18.3%), isolated nodules in 6 (3.9%), mediastinal enlargement in 4 (2.6%) and miliary pattern in 4 (2.6%). Cavities were present in 45.5% of the patients with pulmonary lesions, generally in association with the parenchymal-infiltrate lesions. Parenchymal infiltrate was present in 86.8% of the patients with pulmonary lesions. There was significant presence of alcohol-acid resistant bacillus in the sputum of patients with cavities (76.4%), in comparison with those without cavities (50%) (p = 0.003). CONCLUSIONS: Parenchymal-infiltrate lesions are the most frequent radiological manifestation of pulmonary tuberculosis, and they are generally associated with cavities. There is a relationship between the presence of acid fast bacilli in sputum and pulmonary cavity lesions.

INTESTINAL AND PULMONARY INFECTION BY Cryptosporidium parvum IN TWO PATIENTS WITH HIV/AIDS

We describe two patients with HIV/AIDS who presented pulmonary and intestinal infection caused by Cryptosporidium parvum, with a fatal outcome. The lack of available description of changes in clinical signs and radiographic characteristics of this disease when it is located in the extra-intestinal region causes low prevalence of early diagnosis and a subsequent lack of treatment.

Pulmonary adiaspiromycosis: report of two cases

Two cases of human pulmonary adiaspiromycosis are reported. Patients were 29 and 54-year-old males, farm workers, with "grippe-like" symptoms and radiographic findings suggestive of granulomatous interstitial disease. Transthoracoscopic and transbronchial biopsies were performed. Pulmonary function was measured by spirometry. One patient used ketoconazole. Possibility of misdiagnosed pulmonary adiaspiromycosis is emphasized.

Clinicopathological and immunohistochemical featuresof the severe pulmonary form of leptospirosis

Four cases of severe pulmonary form of leptospirosis (SPFL) are described. In all four of these blood culture proven cases, there was severe pulmonary injury characterized by alveolar hemorrhage and acute respiratory failure. Three patients died in less than 48 hours after onset of the first respiratory signs. Leptospiral antigen detection in lung tissues was positive by immunoperoxidase in all three of these cases, suggesting that the microorganism exerts a local direct destructive action. Patients with SPFL should be carefully monitored, as the abrupt onset of severe alveolar hemorrhage can lead to respiratory insufficiency and death. The authors emphasize the importance of radiological findings and blood gas analysis for prompt clinical diagnosis, and suggest that corticosteroids, associated with antibiotics, early respiratory support, and platelet transfusions are useful as an attempt to prevent further development of SPFL.