Lair Zambon

Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: A phase i pilot study

BackgroundOverall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients.MethodsFive HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 × 107 DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively.ResultsThe dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together.ConclusionDespite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment.Trial RegistrationCurrent Controlled Trials: ISRCTN45563569

Influence of p53 codon 72 exon 4, GSTM1, GSTT1 and GSTP1{*}B polymorphisms in lung cancer risk in a Brazilian population

PURPOSE Glutathione S-transferases (GST) modulates the effects of various cytotoxic and genotoxic agents, particularly those derived from benzo[a]pyrene, which is one of the main tobacco carcinogens. Both the mu 1 (GSTM1) and theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The GSTP1*B allele has an A to G transition at nucleotide 313 (codon 105) in exon 5, causing a change of isoleucine (Ile) to valine (Val), which affects the electrophile binding site of GSTP1 and results in an enzyme with reduced activity. Polymorphisms in these metabolizing enzymes may alter the response to benzo[a]pirene-induced DNA damage. Polymorphisms in p53 may also modulate the risk of lung cancer (LC) carcinogenesis. The aim of our study was to measure the frequency of GSTM1, GSTT1, GSTP1*B and p53 gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to LC risk. PATIENTS AND METHODS Genomic DNA was obtained from 200 Brazilian patients with LC and 264 blood donors (control group). All samples were analyzed by PCR and PCR-RFLP to determine GSTM1, GSTT1, GSTP1*B and p53 codon 72 genotypes. Multiple logistic regressions were used to adjust for confounding factors in this case-control study. RESULTS No statistical significance was observed between GSTM1, GSTT1 and GSTP1*B genetic polymorphisms, either isolated or combined, with LC incidence in the studied population. However, our data showed a higher frequency of p53 codon 72 A/P plus P/P genotype in African-Brazilian than Caucasian-Brazilian patients with LC, and we also found a higher frequency of the P/P genotype of the p53 gene in non-smokers compared to smokers with LC. CONCLUSIONS Genetic polymorphisms of GST and p53 codon 72 did not increase the risk of LC in Brazilian patients. The A/P plus P/P genotype of p53 codon 72 is more common in LC patients with African ethnical background and the P/P genotype more prevalent in non-smoking related LC.

Pulmonary silicosis and systemic lupus erythematosus in men: a report of two cases

We reporttwo cases of coexistence of pulmonary silicosis and systemic lupus erythematosus (SLE). The patients are two men with SLE exposed to silica for 20 years. The hypothesis that silica exposure is linked to a wide variety of known or suspected autoimmune diseases, including SLE, has been discussed in the last decade but few cases of pulmonary silicosis and SLE were reported. Our purpose was to bring attention to the increasing evidence that silica may also cause or stimulate SLE, and to suggest that the researchers look for occupational exposure, mainly in male SLE patients.

Polymorphism of the CYP1A1*2A gene and susceptibility to lung cancer in a Brazilian population

OBJECTIVE To estimate and compare the frequency of CYP1A1*2A gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to lung cancer risk. METHODS The study population included 200 patients with lung cancer, and the control group consisted of 264 blood donors. Genomic DNA was obtained from peripheral blood samples. The PCR-RFLP method was used for analysis of the CYP1A1*2A gene. RESULTS There was no statistically significant difference between the lung cancer patients and the controls in terms of the distribution of CYP1A1*2A polymorphisms (p = 0.49). A multivariate logistic regression model analysis by ethnic group revealed that, within the lung cancer group, the CYP1A1*2A genotype CC plus TC was more common among the African-Brazilian patients than among the White patients (adjusted OR = 3.19; 95% CI: 1.53-6.65). CONCLUSIONS The CYP1A1*2A gene cannot be linked with lung cancer risk in Brazilian patients at this time. Larger epidemiologic studies are needed in order to establish whether the CC plus TC polymorphism increases the risk of lung cancer in African-Brazilians.

Clinical variables of preoperative risk in thoracic surgery

CONTEXT Pulmonary complications are the most common forms of postoperative morbidity in thoracic surgery, especially atelectasis and pneumonia. The first step in avoiding these complications during the postoperative period is to detect the patients that may develop them. OBJECTIVE To identify risk variables leading to early postoperative pulmonary complications in thoracic surgery. DESIGN Prospective study. SETTING Hospital das Clínicas, Faculdade de Ciências Médicas, Universidade Estadual de Campinas. PATIENTS 145 patients submitted to elective surgery were classified as low, moderate and high risk for postoperative pulmonary complications using a risk assessment scale. PROCEDURES The patients were followed up for 72 hours after the operation. Postoperative pulmonary complications were defined as atelectasis, pneumonia, tracheobronchitis, wheezing, prolonged intubation and/or prolonged mechanical ventilation. MAIN MEASUREMENTS Univariate analysis was applied in order to study these independent variables: age, nutritional status, body mass index, respiratory disease, smoking habit, spirometry and surgery duration. Multivariate logistic regression analysis was performed in order to evaluate the relationship between independent and dependent variables. RESULTS The incidence of postoperative complications was 18.6%. Multivariate logistic regression analysis showed that the variables increasing the chances of postoperative pulmonary complications were wheezing (odds ratio, OR = 6.2), body mass index (OR = 1.15), smoking (OR = 1.04) and surgery duration (OR = 1.007). CONCLUSION Wheezing, body mass index, smoking and surgery duration increase the chances of postoperative pulmonary complications in thoracic surgery

GSTM1 and codon 72 P53 polymorphism in multiple myeloma

The GSTM1 and GSTT1 genes reduce the effects of exposure to cytotoxic agents. Both genes have a null variant allele in which the entire gene is absent. On the other hand, a common polymorphism of the tumour suppressor P53 gene results in either arginine (A) or proline (P) at amino-acid position 72. The A and P alleles code proteins with distinct functions in apoptosis and DNA repair and have been associated with variable risks for several cancers. However, their roles in multiple myeloma (MM) are still unknown. We tested in study whether the GSTM1, GSTT1 and P53 genotypes altered the risk for MM in Brazilian patients. Genomic DNA from 106 patients and 230 controls were analysed by polymerase chain reaction-based methods for identification of the genotypes. Similar frequencies of the GSTM1, GSTT1 and P53 genotypes were seen in patients and controls. Individuals with the distinct genotypes had similar risks for disease. In contrast, an excess of the GSTM1 null (45.1 vs 17.2%, P = 0.009), the P53 PP+AP (70.4 vs 44.8%, P = 0.041) and the GSTM1 null plus P53 PP+AP (29.6 vs 10.3%, P = 0.004) genotypes were seen in MM patients at stage III compared with those at stages I + II. Our data suggest that the GSTM1, GSTT1 and P53 genotypes do not influence the risk for MM. However, the inherited presence of the variant codon 72 P53 allele, described here for the first time, and the absence of the GSTM1 detoxification pathway, seem to act in disease progression in our country.

Eficácia da reabilitação pulmonar uma vez na semana em portadores de doença pulmonar obstrutiva

Effectiveness of pulmonary rehabilitation once a week for patients with obstructive pulmonary disease Background: Obstructive pulmonary diseases may interfere negatively with patients’ quality of life (QOL). Specific QOL questionnaires such as the Chronic Respiratory Questionnaire (CRQ) have been used to quantify the impact of the disease and measure the effects of different rehabilitation protocols. Objective: To evaluate the effectiveness of pulmonary rehabilitation performed once a week in association with exercises at home among patients with obstructive pulmonary disease, by means of CRQ comparisons, maximum respiratory pressures (MIP and MEP) and six-minute walking distance test (6MWD), before and after treatment. Methods: This study was developed in the physical therapy outpatient clinic of the hospital. Thirty-four patients of both sexes with obstructive pulmonary disease were evaluated, and nineteen (mean age: 60.8 ± 14.2 years) were included in the study. These subjects all underwent physiotherapeutic evaluation and reevaluation with the CRQ and measurements of MIP, MEP and 6MWD. The physical therapy consisted of respiratory, aerobic and resistance exercises once a week for 12 weeks, together with home exercises twice a week. Results: The Wilcoxon test and Spearman correlation were used. Statistically significant differences between evaluations before and after rehabilitation were found for all CRQ domains (p≤ 0.05), MIP (p= 0.01) and MEP (p= 0.002). Conclusion: The proposed program improved QOL and promoted increases in maximum respiratory pressures among these patients with obstructive pulmonary disease, even though the current literature suggests that higher frequency of training is needed.AbstrAct Background: obstructive pulmonary diseases may interfere negatively with patients’ quality of life (Qol). Specific Qol questionnaires such as the Chronic Respiratory Questionnaire (CRQ) have been used to quantify the impact of the disease and measure the effects of different rehabilitation protocols. objective: to evaluate the effectiveness of pulmonary rehabilitation performed once a week in association with exercises at home among patients with obstructive pulmonary disease, by means of CRQ comparisons, maximum respiratory pressures (mIp and mEp) and six-minute walking distance test (6mwd), before and after treatment. methods: this study was developed in the physical therapy outpatient clinic of the hospital. thirty-four patients of both sexes with obstructive pulmonary disease were evaluated, and nineteen (mean age: 60.8 ± 14.2 years) were included in the study. these subjects all underwent physiotherapeutic evaluation and reevaluation with the CRQ and measurements of mIp, mEp and 6mwd. the physical therapy consisted of respiratory, aerobic and resistance exercises once a week for 12 weeks, together with home exercises twice a week. Results: the wilcoxon test and Spearman correlation were used. Statisti-cally significant differences between evaluations before and after rehabilitation were found for all CRQ domains (p≤ 0.05), mIp (p= 0.01) and mEp (p= 0.002). Conclusion: the proposed program improved Qol and promoted increases in maximum respiratory pressures among these patients with obstructive pulmonary disease, even though the current literature suggests that higher frequency of training is needed.

Utilização da ventilação não invasiva em edema agudo de pulmão e exacerbação da doença pulmonar obstrutiva crônica na emergência: preditores de insucesso

Objective: This study analyzed acute respiratory failure caused by acute pulmonary edema, as well as chronic obstructive pulmonary disease exacerbation, that was treated with non-invasive mechanical ventilation to identify the factors that are associated with the success or failure non-invasive mechanical ventilation in urgent and emergency service. Methods: This study was a prospective, descriptive and analytical study. We included patients of both genders aged ≥18 years who used non- invasive mechanical ventilation due to acute respiratory failure that was secondary to acute pulmonary edema or chronic obstructive pulmonary disease exacerbation. Patients with acute respiratory failure that was secondary to pathologies other than acute pulmonary edema and chronic obstructive pulmonary disease or who presented with contraindications for the technique were excluded. Expiratory pressures between 5 and 8 cmH 2 O and inspiratory pressures between 10 and 12 cmH 2 O were used. Supplemental oxygen maintained peripheral oxygen saturation at >90%. The primary outcome was endotracheal intubation. Results: A total of 152 patients were included. The median non-invasive mechanical ventilation time was 6 hours (range 1 - 32 hours) for chronic obstructive pulmonary disease patients (n=60) and 5 hours (range 2 - 32 hours) for acute pulmonary edema patients (n=92). Most (75.7%) patients progressed successfully. However, reduced APACHE II scores and lower peripheral oxygen saturation were observed. These results were statistically significant in patients who progressed to intubation (p 25 rpm, higher APACHE II scores, BiPAP use and chronic obstructive pulmonary disease diagnosis were associated with endotracheal intubation. Higher GCS and SpO 2 values were associated with NIV success. Non- invasive mechanical ventilation can be used in emergency services in acute respiratory failure cases caused by acute pulmonary edema and chronic obstructive pulmonary disease exacerbation, but patients with variables related to a higher percentage of endotracheal intubation should be specially monitored.

Alveolar hemorrhage after parenteral injection of industrial silicone.

A previously healthy 24-year-old male-to-female transsexual presented with a 48-h history of dyspnea, fever, and signs of severe hypoxemia (SpO 2 , 72%). The patient reported having undergone an illegal procedure 10 days prior, when industrial liquid silicone had been injected into her buttocks for cosmetic purposes. The patient had previously received silicone breast implants. After admission, the patient rapidly evolved to severe respiratory failure and required mechanical ventilation. During intubation and throughout the period on mechanical ventilation, pulmonary bleeding was observed. Her hemoglobin level was 6 g/dL (hematocrit, 18%), and she was given a blood transfusion. Her platelet count, partial thromboplastin time, and prothrombin time were all normal. Chest CT scans showed patchy, bilateral ground-glass opacities, suggestive of alveolar hemorrhage, and bibasilar consolidations (Figure 1). Mild bilateral pleural effusion was also observed. Ultrasound examination of the site of the injection showed no abnormal liquid collection that would require drainage or any other type of surgical intervention. Because of the severe hypoxemia, bronchoscopy and BAL were not performed. Blood cultures were negative throughout the treatment period. The patient was given a diagnosis of silicone pulmonary embolism with alveolar hemorrhage, which was initially treated with mechanical ventilation, accompanied by methylprednisolone pulse therapy, together with a 14-day course of empirical antimicrobial therapy (with oxacillin and ceftriaxone). The evolution was favorable, her hemoglobin level gradually returning to a value that was within the normal range (11.4 g/dL). On post-admission day 14, she was extubated and her SpO 2 was 91%. On post-admission day 21, her overall health status was good and she was discharged. Silicone is the chemical and commercial name for polydimethylsiloxane (dimethicone), an organic compound comprising a chain of alternating silicon and oxygen atoms bonded to other organic groups. The chemical state of the polymer—gel (elastomer), liquid, or solid—is determined by the number of cross-links in the molecule. It has been long considered an inert compound with good thermal stability, favoring its use in medicine in various implantable devices. In its pure form, silicone has been used in cosmetic and esthetic procedures for the last five decades, and it is known to produce minimal tissue reactions and no significant immune response, although, in many countries, it is approved only for use in breast augmentation devices and is prohibited as an injectable liquid. However, the widespread underground practice of industrial liquid silicone injection within the transsexual community worldwide has produced various cases …

Evolução do status de performance, índice de massa corpórea e distância percorrida no teste de caminhada de seis minutos em pacientes com câncer de pulmão avançado submetidos à quimioterapia

OBJECTIVE: To evaluate the effect of chemotherapy on the physical condition of patients with advanced lung cancer. METHODS: We evaluated 50 patients with non-small cell lung cancer (in stages IIIB and IV) and Eastern Cooperative Oncology Group (ECOG) performance status scale scores between zero and two. All patients underwent chemotherapy using paclitaxel and platinum derivatives and were evaluated at three time points (prechemotherapy, postchemotherapy and six months after starting the treatment), at which the ECOG scale, the body mass index (BMI) and the six-minute walk distance (6MWD) were assessed. RESULTS: Of the 50 patients included in the study, 14 died, 5 were excluded due to the worsening of their performance status, and 31 completed the six-month follow-up. There was no statistically significant difference between the time points of assessment for BMI (prechemotherapy vs. postchemotherapy, p = 1.00; and prechemotherapy vs. six months later, p = 0.218) or for 6MWD. Performance status improved, and this was especially due to the increase in the number of asymptomatic patients after the six-month follow-up (p = 0.031). CONCLUSIONS: Chemotherapy had a beneficial effect on the performance status of the patients. No significant changes in BMI or 6MWD were found during the study period, which might suggest the maintenance of the physical condition of the patients.