Aspergillus niger causing tracheobronchitis and invasive pulmonary aspergillosis in a lung transplant recipient: case report

A case of invasive aspergillosis caused by Aspergillus niger in a lung transplant recipient is described. The patient presented hyperglycemia starting postoperatively, with other complications such as cytomegalovirus infection. The associated predisposing factors and other implications are discussed. Aspergillus niger seems to be a fungal species of low virulence that requires the presence of a severely immunosuppressed host to cause invasive disease.

Chemotherapy versus best supportive care in stage IV non-small cell lung cancer, non metastatic to the brain

Stage IV non-small cell lung cancer is a fatal disease, with a median survival of 14 months. Systemic chemotherapy is the most common approach. However the impact in overall survival and quality of life still a controversy. OBJECTIVES: To determine differences in overall survival and quality of life among patients with stage IV non-small cell lung cancer non-metastatic to the brain treated with best supportive care versus systemic chemotherapy. PATIENTS: From February 1990 through December 1995, 78 eligible patients were admitted with the diagnosis of stage IV non-small cell lung cancer . Patients were divided in 2 groups: Group A (n=31 -- treated with best supportive care ), and Group B (n=47 -- treated with systemic chemotherapy). RESULTS: The median survival time was 23 weeks (range 5 -- 153 weeks) in Group A and 55 weeks (range 7.4 -- 213 weeks) in Group B (p=0.0018). In both groups, the incidence of admission for IV antibiotics and need of blood transfusions were similar. Patients receiving systemic chemotherapy were also stratified into those receiving mytomycin, vinblastin, and cisplatinum, n=25 and those receiving other combination regimens (platinum derivatives associated with other drugs, n=22). Patients receiving mytomycin, vinblastin, and cisplatinum, n=25 had a higher incidence of febrile neutropenia and had their cycles delayed for longer periods of time than the other group. These patients also had a shorter median survival time (51 versus 66 weeks, p=0.005). CONCLUSION: In patients with stage IV non-small cell lung cancer, non-metastatic to the brain, chemotherapy significantly increases survival compared with best supportive care.

Thumb metastasis from small cell lung cancer treated with radiation

A rare case of thumb metastasis from small cell lung cancer is presented. The patient underwent local radiotherapy with complete palliation of symptoms. She died 4 months later with disseminated disease. Considerations about incidence, treatment, and physiopathology of this kind of dissemination are made. Conservative treatment of finger metastasis with radiation may be considered due to the poor outcome of these patients.

Detection of coronary artery disease based on the calcification index obtained by helical computed tomography

OBJECTIVE: To assess the relation between coronary artery disease and the calcification index on helical computed tomography. METHOD: We studied 22 patients (ages ranging from 40 to 70 years) who underwent coronary angiography because of chest pain suggestive of angina pectoris. Findings on coronary angiography were classified as follows: significant obstructive disease (stenosis > or = 50%), nonobstructive disease (stenosis <50%), and no disease. With no previous knowledge of the results of the coronary angiography and within 7 days, helical computed tomography of the chest was performed. Then, data of the coronary angiography were correlated with the calcification index obtained by helical computed tomography. RESULTS: The sensitivity of helical computed tomography to the presence of significant obstructive lesions on coronary angiography was 87.5%, specificity was 100%, and negative and positive predictive values were 75% and 100%, respectively. The mean calcification index was greater in patients with severe coronary lesions, mainly when involvement of 2 or 3 vessels occurred, than that in patients with no coronary artery disease or with nonobstructive coronary artery lesions (p<0.05). CONCLUSION: Helical computed tomography is an effective method for detecting and quantifying coronary artery calcification, and it has proved to be sensitive to and specific for the noninvasive diagnosis of coronary artery stenosis.

Palliative Senning in the Treatment of Congenital Heart Disease with Severe Pulmonary Hypertension

Background:Transposition of the great arteries (TGA) is the most common cyanotic cardiopathy, with an incidence ranging between 0.2 and 0.4 per 1000 live births. Many patients not treated in the first few months of life may progress with severe pulmonary vascular disease. Treatment of these patients may include palliative surgery to redirect the flow at the atrial level.Objective:Report our institutional experience with the palliative Senning procedure in children diagnosed with TGA and double outlet right ventricle with severe pulmonary vascular disease, and to evaluate the early and late clinical progression of the palliative Senning procedure.Methods:Retrospective study based on the evaluation of medical records in the period of 1991 to 2014. Only patients without an indication for definitive surgical treatment of the cardiopathy due to elevated pulmonary pressure were included.Results:After one year of follow-up there was a mean increase in arterial oxygen saturation from 62.1% to 92.5% and a mean decrease in hematocrit from 49.4% to 36.3%. Lung histological analysis was feasible in 16 patients. In 8 patients, pulmonary biopsy grades 3 and 4 were evidenced.Conclusion:The palliative Senning procedure improved arterial oxygen saturation, reduced polycythemia, and provided a better quality of life for patients with TGA with ventricular septal defect, severe pulmonary hypertension, and poor prognosis.

Efficacy of Patient Selection for Diagnostic Coronary Angiography in Suspected Coronary Artery Disease

AbstractBackground:Guidelines recommend that in suspected stable coronary artery disease (CAD), a clinical (non-invasive) evaluation should be performed before coronary angiography.Objective:We assessed the efficacy of patient selection for coronary angiography in suspected stable CAD.Methods:We prospectively selected consecutive patients without known CAD, referred to a high-volume tertiary center. Demographic characteristics, risk factors, symptoms and non-invasive test results were correlated to the presence of obstructive CAD. We estimated the CAD probability based on available clinical data and the incremental diagnostic value of previous non-invasive tests.Results:A total of 830 patients were included; median age was 61 years, 49.3% were males, 81% had hypertension and 35.5% were diabetics. Non-invasive tests were performed in 64.8% of the patients. At coronary angiography, 23.8% of the patients had obstructive CAD. The independent predictors for obstructive CAD were: male gender (odds ratio [OR], 3.95; confidence interval [CI] 95%, 2.70 - 5.77), age (OR for 5 years increment, 1.15; CI 95%, 1.06 - 1.26), diabetes (OR, 2.01; CI 95%, 1.40 - 2.90), dyslipidemia (OR, 2.02; CI 95%, 1.32 - 3.07), typical angina (OR, 2.92; CI 95%, 1.77 - 4.83) and previous non-invasive test (OR 1.54; CI 95% 1.05 - 2.27).Conclusions:In this study, less than a quarter of the patients referred for coronary angiography with suspected CAD had the diagnosis confirmed. A better clinical and non-invasive assessment is necessary, to improve the efficacy of patient selection for coronary angiography.

Prevalence of Risk for Obstructive Sleep Apnea Syndrome and Association With Risk Factors in Primary Care

Abstract Background: Obstructive sleep apnea syndrome (OSAS) is a chronic, progressive disease with high morbidity and mortality. It is underdiagnosed, especially among women. Objective: To study the prevalence of high risk for OSAS globally and for the Berlin Questionnaire (BQ) categories, and to evaluate the reliability of the BQ use in the population studied. Methods: Observational, cross-sectional study with individuals from the Niterói Family Doctor Program, randomly selected, aged between 45 and 99 years. The visits occurred between August/2011 and December/2012. Variables associated with each BQ category and with high risk for OSAS (global) were included in logistic regression models (p < 0.05). Results: Of the total (616), 403 individuals (65.4%) reported snoring. The prevalence of high risk for OSA was 42.4%, being 49.7% for category I, 10.2% for category II and 77.6% for category III. Conclusion: BQ showed an acceptable reliability after excluding the questions Has anyone noticed that you stop breathing during your sleep? and Have you ever dozed off or fallen asleep while driving?. This should be tested in further studies with samples mostly comprised of women and low educational level individuals. Given the burden of OSAS-related diseases and risks, studies should be conducted to validate new tools and to adapt BQ to better screen OSAS.

Phenotypes of lung mononuclear phagocytes in HIV seronegative tuberculosis patients: evidence for new recruitment and cell activation

Mycobacterium tuberculosis preferentially resides in mononuclear phagocytes. The mechanisms by which mononuclear phagocytes keep M. tuberculosis in check or by which the microbe evades control to cause disease remain poorly understood. As an initial effort to delineate these mechanisms, we examined by immunostaining the phenotype of mononuclear phagocytes obtained from lungs of patients with active tuberculosis. From August 1994 to March 1995, consecutive patients who had an abnormal chest X-ray, no demostrable acid-fast bacilli in sputum specimens and required a diagnostic bronchoalveolar lavage (BAL) were enrolled. Of the 39 patients enrolled, 21 had microbiologically diagnosed tuberculosis. Thirteen of the 21 tuberculosis patients were either HIV seronegative (n = 12) or had no risk factor for HIV and constituted the tuberculosis group. For comparison, M. tuberculosis negative patients who had BAL samples taken during this time (n = 9) or normal healthy volunteers (n = 3) served as control group. Compared to the control group, the tuberculosis group had significantly higher proportion of cells expressing markers of young monocytes (UCHM1) and RFD7, a marker for phagocytic cells, and increased expression of HLA-DR, a marker of cell activation. In addition, tuberculosis group had significantly higher proportion of cells expressing dendritic cell marker (RFD1) and epithelioid cell marker (RFD9). These data suggest that despite recruitment of monocytes probably from the peripheral blood and local cell activation, host defense of the resident lung cells is insufficient to control M. tuberculosis.

Clinical and pathological study of an outbreak of obstructive urolithiasis in feedlot cattle in southern Brazil

The epidemiology, clinical picture and pathology of an outbreak of urolithiasis in cattle in southern Brazil are described. The disease occurred in August 1999 in a feedlot beef cattle herd. Five out of 1,100 castrated steers were affected. Clinical signs included colic and ventral abdominal distension. White, sand-grain-like mineral deposits precipitated on the preputial hairs. Affected cattle died spontaneously 24-48 hrs after the onset of the clinical signs. Only one animal recovered after perineal urethrostomy. Necropsy findings included calculi blocking the urethral lumen of the distal portion of the penile sigmoid flexure, urinary bladder rupture with leakage of urine into the abdominal cavity and secondary fibrinous peritonitis. Daily water intake was low since water sources were scarce and not readily available. The animals were fed rations high in grains and received limited amounts of roughage. Biochemical analysis revealed that the calculi were composed of ammonium phosphate. A calcium-phosphorus imbalance (0.4:0.6) was detected in the feedlot ration. For the outbreak, it is suggested that contributing factors to urolith formation include insufficient fiber ingestion, low water intake and high dietary levels of phosphorus. No additional cases were observed in that feedlot after preventive measures were established. Similar dietary mismanagement in fattening steers has been associated with obstructive urolithiasis in feedlot beef cattle in other countries.

Nested-PCR for the detection of Mycoplasma hyopneumoniae in bronchial alveolar swabs, frozen tissues and formalin-fixed paraffin-embedded swine lung samples: comparative evaluation with immunohistochemical findings and histological features

The diagnosis of Mycoplasma hyopneumoniae infection is often performed through histopathology, immunohistochemistry (IHC) and polymerase chain reaction (PCR) or a combination of these techniques. PCR can be performed on samples using several conservation methods, including swabs, frozen tissue or formalin-fixed and paraffin-embedded (FFPE) tissue. However, the formalin fixation process often inhibits DNA amplification. To evaluate whether M. hyopneumoniae DNA could be recovered from FFPE tissues, 15 lungs with cranioventral consolidation lesions were collected in a slaughterhouse from swine bred in herds with respiratory disease. Bronchial swabs and fresh lung tissue were collected, and a fragment of the corresponding lung section was placed in neutral buffered formalin for 48 hours. A PCR assay was performed to compare FFPE tissue samples with samples that were only refrigerated (bronchial swabs) or frozen (tissue pieces). M. hyopneumoniae was detected by PCR in all 15 samples of the swab and frozen tissue, while it was detected in only 11 of the 15 FFPE samples. Histological features of M. hyopneumoniae infection were presented in 11 cases and 7 of these samples stained positive in IHC. Concordance between the histological features and detection results was observed in 13 of the FFPE tissue samples. PCR was the most sensitive technique. Comparison of different sample conservation methods indicated that it is possible to detect M. hyopneumoniae from FFPE tissue. It is important to conduct further research using archived material because the efficiency of PCR could be compromised under these conditions.

Lung tissue mechanics in the early stages of induced paracoccidioidomycosis in rats

Pulmonary dysfunction represents the most important cause of death in patients with paracoccidioidomycosis (PBM). In order to investigate the functional changes of the lungs in the early stages of PBM, a model of benign disease was developed by intratracheal challenge of 12-week old isogenic Wistar rats with 1 x 106 yeast forms of Paracoccidioides brasiliensis. Animals were studied 30 and 60 days after infection, when fully developed granulomas were demonstrable in the lungs. Measurements of airway resistance, lung elastance and tissue hysteresis were made during sinusoidal deformations (100 breaths/min, tidal volume = 2 ml) with direct measurement of alveolar pressure using the alveolar capsule technique. Infection caused a significant increase in hysteresis (infected: 1.69, N = 13; control: 1.13, N = 12, P = 0.024, ANOVA), with no alterations in airway resistance or lung elastance. Histopathological analysis revealed the presence of fully developed granulomas located in the axial compartment of the lung interstitial space. These results suggest that alterations of tissue mechanics represent an early event in experimental PBM

Assessment of ventilatory neuromuscular drive in patients with obstructive sleep apnea

The presence of abnormalities of the respiratory center in obstructive sleep apnea (OSA) patients and their correlation with polysomnographic data are still a matter of controversy. Moderately obese, sleep-deprived OSA patients presenting daytime hypersomnolence, with normocapnia and no clinical or spirometric evidence of pulmonary disease, were selected. We assessed the ventilatory control and correlated it with polysomnographic data. Ventilatory neuromuscular drive was evaluated in these patients by measuring the ventilatory response (VE), the inspiratory occlusion pressure (P.1) and the ventilatory pattern (VT/TI, TI/TTOT) at rest and during submaximal exercise, breathing room air. These analyses were also performed after inhalation of a hypercapnic mixture of CO2 (DP.1/DPETCO2, DVE/DPETCO2). Average rest and exercise ventilatory response (VE: 12.2 and 32.6 l/min, respectively), inspiratory occlusion pressure (P.1: 1.5 and 4.7 cmH2O, respectively), and ventilatory pattern (VT/TI: 0.42 and 1.09 l/s; TI/TTOT: 0.47 and 0.46 l/s, respectively) were within the normal range. In response to hypercapnia, the values of ventilatory response (DVE/DPETCO2: 1.51 l min-1 mmHg-1) and inspiratory occlusion pressure (DP.1/DPETCO2: 0.22 cmH2O) were normal or slightly reduced in the normocapnic OSA patients. No association or correlation between ventilatory neuromuscular drive and ventilatory pattern, hypersomnolence score and polysomnographic data was found; however a significant positive correlation was observed between P.1 and weight. Our results indicate the existence of a group of normocapnic OSA patients who have a normal awake neuromuscular ventilatory drive at rest or during exercise that is partially influenced by obesity

Lung clearance of 99mTc-DTPA in systemic lupus erythematosus

The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99mTc-DTPA is increased in SLE patients with active disease.

A comparison of public and private obstructive sleep apnea clinics

The aim of the present study was to compare the clinical findings and polysomnography results obtained at public and private clinics in Brazil, the follow-up after diagnosis, and the therapeutic aspects related to continuous positive airway pressure. Patients who snore and who have obstructive sleep apnea were retrospectively divided into two groups, i.e., public clinic (N = 307) and private clinic (N = 317). Data concerning age, sex, body mass index (BMI), neck circumference, medical history, sleepiness scale, follow-up after diagnosis, and acceptance of continuous positive airway pressure therapy were collected. Mean age was 50 ± 12 (range: 15-80) for public patients and 48 ± 12 years (range: 19-91) for private patients. Mean BMI was 30 ± 6 (range: 19-67) for public patients and 31 ± 6 kg/m² (range: 21-59) for private patients. The public clinic had a significantly higher frequency of women than the private clinic (M:F ratio of 2.0:1 and 6.9:1, respectively). The condition of private patients (apnea-hypopnea index = 31 ± 25) was more severe than that of public patients (apnea-hypopnea index = 25 ± 24 events/h; P = 0.0004). In the public and private clinics, 19 and 15% of patients were snorers, respectively, and 81 and 85% of them had sleep apnea. After diagnosis, follow-up was longer in the private group. The continuous positive airway pressure acceptance was similar for both groups (32 vs 35%), but patients from the public clinic abandoned treatment more than private ones (65 vs 13%). Social status was significant in terms of the severity of obstructive sleep apnea age and gender distribution. Private patients look for a diagnosis earlier in the course of the disease than public patients, adhere more to follow-up, and abandon continuous positive airway pressure treatment less than public patients do.

Antagonist G-mediated targeting and cytotoxicity of liposomal doxorubicin in NCI-H82 variant small cell lung cancer

The aim of the present study was to characterize the interactions of antagonist G (H-Arg-D-Trp-NmePhe-D-Trp-Leu-Met-NH 2)-targeted sterically stabilized liposomes with the human variant small cell lung cancer (SCLC) H82 cell line and to evaluate the antiproliferative activity of encapsulated doxorubicin against this cell line. Variant SCLC tumors are known to be more resistant to chemotherapy than classic SCLC tumors. The cellular association of antagonist G-targeted (radiolabeled) liposomes was 20-30-fold higher than that of non-targeted liposomes. Our data suggest that a maximum of 12,000 antagonist G-targeted liposomes were internalized/cell during 1-h incubation at 37ºC. Confocal microscopy experiments using pyranine-containing liposomes further confirmed that receptor-mediated endocytosis occurred, specifically in the case of targeted liposomes. In any of the previously mentioned experiments, the binding and endocytosis of non-targeted liposomes have revealed to be negligible. The improved cellular association of antagonist G-targeted liposomes, relative to non-targeted liposomes, resulted in an enhanced nuclear delivery (evaluated by fluorimetry) and cytotoxicity of encapsulated doxorubicin for incubation periods as short as 2 h. For an incubation of 2 h, we report IC50 values for targeted and non-targeted liposomes containing doxorubicin of 5.7 ± 3.7 and higher than 200 µM doxorubicin, respectively. Based on the present data, we may infer that receptors for antagonist G were present in H82 tumor cells and could mediate the internalization of antagonist G-targeted liposomes and the intracellular delivery of their content. Antagonist G covalently coupled to liposomal drugs may be promising for the treatment of this aggressive and highly heterogeneous disease.