Association of asthma risk factors and the prevalence of the disease in a population of Brazil.

Summary: The objective of our study was to evaluate the association between the previously described asthma risk factors and the prevalence of asthma in a population of Brazilian adults. A population-based cross-sectional study was conducted using data collected from 7891 patients. All patients in the database > 18 years of age were included. The following variables were collected from the health plan database: age, body mass index, smoking status, alcohol consumption, sedentary lifestyle, heart disease, hypertension, diabetes, and asthma diagnosis. The frequency of the collected variables was compared between patients with or without an asthma diagnosis, and logistic regression was performed. Of our total sample (7891 patients), 150 (1.9%) had asthma. The mean age of patients with asthma was 39.4 years. 1.4% of normal weight patients had the diagnosis of asthma, while 2.4% of overweight and 2.2% of obese patients had the diagnosis. Multivariate analysis demonstrated that a sedentary lifestyle and overweight and obesity were independently associated with asthma prevalence Odds Ratio (OR) (95% confidence interval): (1.61 (1.16-2.22) and 1.25 (1.03-1.52) respectively). Our data provide evidence that some clinical characteristics, such as sedentarism, overweight, and obesity, may be related to the prevalence of asthma in an adult population in southeastern Brazil. Such factors could be modified and better understood through multidisciplinary research and health programs that evaluate the risk factors for asthma in large populations.

Phosphorylation of protein phosphatase-1 inhibitors, inhibitor-1 and DARPP-32, in renal medulla.

Inhibitor-1 and DARPP-32 (dopamine and cAMP-regulated phosphoprotein, Mr 32 kDa) are each phosphorylated by cAMP-dependent protein kinase, resulting in their conversion to potent inhibitors of protein phosphatase-1. Protein phosphatase-1 is involved in the regulation of Na(+) reabsorption from renal tubule by modulating the activity of Na(+),K(+)-ATPase. In this study, we have investigated the regulation of inhibitor-1 and DARPP-32 phosphorylation in slices of renal medulla. Activation of cAMP-dependent protein kinase by forskolin and 8-bromo-cAMP increased the level of phosphorylated inhibitor-1. Okadaic acid (1 microM), used to inhibit protein phosphatase-2A, increased the level of phosphorylated inhibitor-1, but cyclosporin A had no effect. DARPP-32, like inhibitor-1, was phosphorylated by cAMP-dependent protein kinase and dephosphorylated only by protein phosphatase-2A. These data demonstrate that the phosphorylation of inhibitor-1 and DARPP-32 is regulated by the balance of phosphorylation by cAMP-dependent protein kinase and dephosphorylation by protein phosphatase-2A in renal medulla. Furthermore, the phosphorylation step is regulated by pharmacological stimuli such as activation of beta(1)-adrenoceptors and dopamine D1 receptors.

Hormone receptors in pulmonary lymphangiomyomatosis.

Biochemical assays have demonstrated the existence of hormone receptors in lung tissue from patients with pulmonary lymphangiomyomatosis (LAM). This finding is the biologic corollary to the finding that LAM responds to hormonal therapy. We have examined lung tissue from two patients with LAM for estrogen and progesterone receptors by immunohistochemistry and a biochemical assay. Although specimens from both patients were negative for estrogen receptor activity by the biochemical assay, positive stain of estrogen receptors was observed in both patients with immunohistochemistry.

[Evaluation of aerosol therapy of streptomycin for tracheobronchial and pulmonary tuberculosis].

The clinical features of tracheobronchial tuberculosis are distinct from those of pulmonary tuberculosis in some aspects. Streptomycin (SM) is claimed by some investigators that it has a tendency to promote the development of bronchial stenosis due to scarred healing of the involved endobronchial mucosa, and, for that reason, they recommend not to use it in treatment of bronchial tuberculosis. In some patients with pulmonary tuberculosis, who have renal or hearing disturbance, SM avoided. Yet unless SM is used improvement of tuberculosis could be delayed. It is the purpose of the present investigation to point out that aerosol therapy of SM is useful for patients with respiratory tuberculosis. Furthermore, we wish to demonstrate that we can safely treat the patients with respiratory tuberculosis who suffer from renal function or hearing disorder by use of aerosol therapy of SM. Prior to clinical application of the inhalation therapy, we confirmed that the therapy was not harmful. Serum concentration of SM, when inhaled, was measured in 9 volunteers. Before and after administration of SM aerosol, spirograms were examined in 4 volunteers, nevertheless, no special abnormality was recognized. It seemed that serum concentration of SM after the administration was two low to evoke adverse reactions (less than 3.0 gamma). In 6 patients with pulmonary tuberculosis, blood gases were measured and no obvious change was observed. As a result, it was demonstrated that the endobronchial tuberculous lesions improved faster when treated by inhalation of aerosolized SM as compared with the conventional injection therapy, without evoking any apparent adverse reactions. In some of the patients with pulmonary tuberculosis, it seemed that the therapy was useful.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of anti-glomerular basement membrane antibody (AGBMA) nephritis associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)].

A 68-year-old patient visited our hospital, because of progressive renal failure. Laboratory data were serum creatinine 13.3 mg/dl, BUN 74.3 mg/dl, AGBMA 134U, MPO-ANCA 37% and CIC 1.6 g/dl. Hemodialysis was performed on admission and renal biopsy was conducted. Though the histological findings showed fibrocellular crescents and global sclerosis in many glomeruli, renal function was gradually ameliorated by administration of prednisolone (40 mg/day) and cyclophosphamide (50 mg/day). After 3 weeks of therapy, hemodialysis was withdrawn temporarily. Because of the complication of pneumocystis carini, prednisolone and cyclophosphamide were discontinued, and maintenance hemodialysis was resumed. In spite of progressed histological findings, hemodialysis was withdrawn at least temporarily through the use of pharmacological therapy. Thus, the presence of ANCA may indicate a relatively good prognosis of AGBMA nephritis.

[Clinical study of laryngeal cancer].

An analysis of 74 patients with laryngeal cancer treated between February 1985 and July 1995 is presented. Their mean age was 64 years, and the male to female ratio was 14:1. There were 48 cases of the glottic type, 21 cases of the supraglottic type, 2 cases of the subglottic type, and 3 cases of the transglottic type. Histopathologically, there were 72 cases of squamous cell carcinoma and 2 cases of mucoepidermoid carcinoma. Cervical lymph node metastasis was detected in 12 cases (16%). The incidence of cervical lymph node metastasis in supraglottic carcinoma was significantly higher (p < 0.01) than that in glottic carcinoma. There were 12 cases of second primary cancers. The location of the lesions was as follows: lung, 4; esophagus, 2; stomach, 2; prostate, 2; liver, 1; and gingiva, 1. Radical radiotherapy was performed in 52 cases; the local control rate was 98%, and the recurrence rate was 20%. Combined radiotherapy and total laryngectomy or laryngectomy alone was performed in 23 cases, and the recurrence rate was 23%. The recurrence rate for glottic carcinoma after initial therapy was 13%, supraglottic carcinoma 38%, subglottic carcinoma 100% and transglottic carcinoma 33%. Five-year total survival and cause-specific survival rate were 69% and 82%, respectively. Five-year cause-specific survival rates according to subsite were 95% for glottic carcinoma, 69% for supraglottic carcinoma, 0% for subglottic carcinoma, and 50% for transglottic carcinoma. The survival rate in glottic carcinoma was significantly better (p < 0.05) than in supraglottic carcinoma. These results led us to establish the following guidelines for the treatment of laryngeal cancer: for T1 or T2 cases of the glottic type, radiotherapy is recommended first; for T3 or T4 cases of the glottic type, total laryngectomy after radiation therapy is recommended; for T1 or T2N0 cases of the supraglottic type, radiotherapy is recommended first; for T2N(+) or T3 or T4 cases of the supraglottic type, total laryngectomy after radiation therapy is recommended. If cervical lymph node metastasis is presently, neck dissection is necessary.

[Outcome of hypopharyngeal cancer].

An analysis of 41 patients with hypopharyngeal cancer treated between April 1985 and March 1996 is presented. Our guidelines for the treatment of hypopharyngeal cancer are a combination of chemotherapy, radiotherapy and surgery. The schedule of combination therapy is as follows: chemotherapy first, preoperative radiotherapy second, and surgery last. The surgery for hypopharyngeal cancer is pharyngolaryngoesophagectomy with radical neck dissection. In many cases free jejunum transplantation was used for reconstruction. The mean age of the patients was 64.8 years, and there were 39 men and 2 women. There were 33 cases of pyriform sinus type, 4 cases of postcricoid type, 3 cases of retropharyngeal type, and 1 case of unclassified type. Histopathologically, there were 40 cases of squamous cell carcinoma and 1 case of anaplastic carcinoma. Five-year total survival rates were 23.0% and 5-year survival rates at each tumor stage were 0% (T-1), 19.9% (T-2), 32.4% (T-3), 0% (T-4). There were no statistically significant differences between tumor stages. Five-year survival rates for each nodal stage were 14.1% (N-0), 54.5% (N-1), 0% (N-2), 0% (N-3). The survival rate for stage N-1 was significantly better (p < 0.05) than that for stage N-2. Five-year survival rates for all stages were 0% (I), 0% (II), 46.3% (III), 0% (IV). The survival rate for stage III was significantly better (p < 0.05) than that for stage IV. Twenty-five patients were operated on with or without chemotherapy and radiotherapy and, 16 patients received nonsurgical treatment. The 5-year cause-specific survival rate for patients who underwent surgery was 57.7% and for patients who underwent nonsurgical treatment was 0%. The survival rate for the radical treatment group was significantly better (p < 0.05) than that for the nonradical treatment group. The 5-year cause-specific survival rate for patients who underwent radical radiotherapy was 0%. That for patients who were treated by chemotherapy was 51.4% and for patients who were not so treated was 20.1%. The results of this study suggest several significant conclusions: 1, Stage is not a good predictor of outcome in hypopharyngeal cancer. 2, Patients undergoing surgery with or without chemotherapy and radiotherapy as the primary treatment enjoyed improved survival. 3, Radical radiotherapy provided poor prognosis. We think that chemotherapy provided some survival benefit.

[Clinical study of subglottic carcinoma].

Recently, therapy for laryngeal carcinoma has been becoming established, particularly in the early stage. The prognosis of laryngeal carcinoma is said to be better than that of other head and neck carcinomas. Laryngeal carcinoma is divided into 3 subtypes, supraglottic, glottic and subglottic, according to origin. We analyzed the subglottic carcinomas diagnosed and treated in our department between 1972 and 1990. During that period we treated 515 cases of laryngeal carcinoma, 204 cases of the supraglottic type, 284 cases of the glottic type, and 27 cases (5.2%) of the subglottic type. The 5-year survival rate in subglottic carcinoma was 44% (T1: 83%, T2:55%, T3: 17%, T4: 0%), worse than in the other types of laryngeal carcinoma. We think that there were 2 main reasons for the worse prognosis. The first was their high rate of local recurrence after radiation therapy particularly in the early stage. Although 15 T1 and T2 patients who received full dose (65Gy) radiotherapy had a complete response, 8 patients developed local recurrence. The results of the salvage operation were good in T1 cases, but were followed by death because of metastasis or second recurrence in 2 of the 3 T2 patients. The second reason for the worse prognosis appeared to be metastasis in the advanced cases. Five (50%) T3 and T4 patients developed metastasis to the lung, mediastinum and cervical lymph nodes, resulting in death. Thus, we believe that the main therapy for subglottic carcinoma, except T1, should be surgery to obtain a better outcome, and that adjuvant chemotherapy after irradiation or neck (paratracheal) dissection with total laryngectomy should be performed in advanced cases.

[Up-regulation of human chorionic gonadotropin alpha subunit gene and human mitochondrial cytochrome c oxidase subunit II gene in cis-Diamminedichloroplatinum(II)-resistant human head and neck squamous carcinoma cells].

The resistance of head and neck squamous carcinoma cells (HNSCCs) to cis-Diamminedichloroplatinum(II) (CDDP), which is widely used for the treatment of many malignancies, is a serious problem in the clinic. The mechanism by which cancer cells get resistant to this compound has not been completely understood. To elucidate the mechanism, we compared gene expression in the cells sensitive to CDDP with that in the resistant variants using fluorescent differential display technique. Side-by-side comparison on a sequence gel demonstrated that 105 genes were differentially expressed between KB, a human oral SCC line, and KB/cDDP, which was developed from KB and shows 2.5-fold increases in resistance to CDDP, as well as between HEp2, a human laryngeal SCC line, and its cDDP-resistant variants. Several candidates for the CDDP resistance related genes have been cloned by the following re-amplifications. Northern blot analysis revealed that human chorionic gonadotropin alpha subunit gene and human mitochondrial cytochrome c oxidase subunit II gene were expressed higher in KB/cDDP than in KB parental cells. Our results suggest that these two genes are associated with CDDP resistance and that human chorionic gonadotropin alpha subunit gene product is potentially a clinical biomarker for the resistance to CDDP.

Production of granulocyte colony-stimulating factor by malignant mesothelioma.

We present the case of a male patient, aged 45 yrs, with malignant mesothelioma producing granulocyte colony-stimulating factor (G-CSF). The diagnosis was established by histopathological examination of the autopsied pleural tissues. Production of G-CSF was confirmed by immunoperoxidase staining, using a specific monoclonal antibody against recombinant G-CSF (rhG-CSF).

Synthesis and characterization of bis(mu-hydroxo)diiron(III) complex of N-(4-nitro-2-hydroxy)phenylmethyl-N-(2-pyridylethyl)-N-(2-pyridylmethyl)amine and hydroxylation reaction of alkane.

Bis(mu-hydroxo)diiron(III) complex, [Fe2III(mu-OH)2(NE)2](NO3)2 x 3H2O (3) (N-(4-nitro-2-hydroxy)phenylmethyl-N-(2-pyridylethyl)-N-(2-pyridylmethyl)amine = HNE, where H denotes a dissociable proton of the p-nitrophenol group), has been prepared and characterized by X-ray crystallography, electronic and magnetic spectroscopies.

[A case of dimethyl sulfate intoxication manifested by persistent dyspnea].

A 35-year-old man had been exposed to the vapor of dimethyl sulfate which was split over the bed of a truck from an accidentally broken container. After receiving treatment at the critical care unit of our university hospital for respiratory failure, he was transferred to our ward with dyspnea persisting for one month. Chest X-ray showed diffuse nodular and infiltrative shadows and shadows suggestive of bronchial wall thickening. Bronchoscopy demonstrated tracheobronchial stenosis due to severe inflammation, and transbronchial lung biopsy revealed erosion and granulation in tissues of the bronchiolar walls. These findings suggested extensive inflammatory involvement of the respiratory tract extending from the trachea to the bronchioles. Treatment with antibiotics, especially agents with antipseudomonal activity, was effective against secondary pneumonia. Administration of corticosteroid for stenotic lesions of the airway was extremely beneficial. The clinical course of the respiratory lesion caused by dimethyl sulfate intoxication was following, including the bronchoscopic findings. The efficacy of treatment with corticosteroid and antibiotics was evaluated by successive bronchoscopic examinations of the lesions.

[Lymphocyte phenotype and cytokine mRNA expression of steady-state asthma BALF cells].

Recently, the roles of inflammatory processes in the pathogenesis of asthma have been emphasized. To elucidate the roles of T lymphocytes in local inflammatory sites in asthma, we examined T cell phenotypes with flow cytometry and carried out cytokine message amplification phenotyping (MAPPing) of bronchoalveolar lavage (BAL) cells taken from patients with steady-state asthma (n = 11). The percentage of CD4+ T cells in total lymphocytes correlated significantly (r = 0.784, p < 0.005) with that of lymphocytes in total CD45+ BAL cells. The positivities of T cell activation markers (CD25, HLA-DR) in CD4+ T cells were inversely correlated with the ratio of CD3+ T cells to total CD45+ BAL cells (CD25, r = 0.648, p = -0.059, HLA-DR, r = -0.741, p < 0.05). Most CD4+ T cells were of the CD45 RO+ "memory" phenotype. With cytokine MAPPing, IL-2 or IFN gamma were detected in only 2 of 11 patients, but IL4 or IL-5 were detected in 8 patients. These results suggest that non-activated TH2 type memory CD4+ T cells accumulate in local inflammatory sites of the bronchi of patients with steady-state asthma, and that these cells releases cytokines (IL-4, IL-5) when activated by some stimuli, which can lead to an asthma attack.

[A case of sarcoidosis presenting with hoarseness and dysphagia due to glossopharyngeal and vagus nerve paresis].

The patient was a 20-year-old female who complained of hoarseness and dysphagia. Chest X-ray showed bilateral hilar lymphadenopathy. Sarcoidosis was diagnosed histologically on the basis of granuloma without necrosis, by transbronchial lung biopsy (TBLB). Bronchofiberscopic findings revealed no granuloma of the vocal cords. Examination of the central nervous system with MRI identified no abnormalities. Hoarseness and dysphagia were thought to have been caused by glossopharyngeal and vagus nerve paresis. These signs improved markedly after two weeks of steroid therapy. This is a rare case of sarcoidosis associated with glossopharyngeal & vagus nerve paresis.