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Biomedical subjects

R Bueno

Publications and source records attributed to R Bueno.

At least 19 recordsLinked to original sources

Phenotypic, functional, and quantitative characterization of canine peripheral blood monocyte-derived macrophages.

The yield as well as phenotypic and functional parameters of canine peripheral blood monocyte-derived macrophages were analyzed. The cells that remained adherent to Teflon after 10 days of culture had high phagocytic activity when inoculated with Leishmania chagasi. Flow cytometric analysis demonstrated that more than 80% of cultured cells were positive for the monocyte/macrophage marker CD14.

Animals↗

Genital lesions associated with visceral leishmaniasis and shedding of Leishmania sp. in the semen of naturally infected dogs.

Although visceral leishmaniasis is primarily transmitted by a biological invertebrate vector, transmission in the absence of the vector has been reported, including venereal transmission in humans. Considering the possibility of venereal transmission, we studied genital lesions in dogs naturally infected with visceral leishmaniasis and shedding of Leishmania sp. in the semen. Approximately 200 dogs were serologically tested for anti-Leishmania antibodies and divided into three groups: 1) serologically negative dogs (n = 20), 2) asymptomatic serologically positive dogs (n = 20), and 3) symptomatic serologically positive dogs (n = 20). Samples from both testes, all segments of both epididymes, prostate gland, glans penis, and prepuce were histologically evaluated and processed for immunodetection of Leishmania sp. Semen samples were obtained from 22 symptomatic serologically positive dogs and processed for detecting Leishmania DNA by polymerase chain reaction. A significantly higher frequency of inflammation was observed in the epididymes, glans penis, and prepuce of dogs with visceral leishmaniasis, which was associated with a high frequency of immunohistochemically positive tissues (up to 95% of tissues from symptomatic dogs were positive by immunohistochemistry). Leishmania DNA was detected in eight of 22 semen samples from symptomatic dogs. Together these findings indicate that genital lesions and shedding of Leishmania sp. (donovani complex) in the semen are associated with visceral leishmaniasis. Additional studies should address the possibility of venereal transmission of the disease in the dog.

Animals↗

Population at risk for eating disorders in a Spanish region.

OBJECTIVE: To estimate the prevalence of adolescent population at risk for eating disorders (EDs), to examine gender differences and their association with non-psychotic mental disorders. METHODS: Cross-sectional study using an anonymous, self-reported questionnaire in the classroom and measurement of weight and height in a representative sample of 4334 teenagers of both sexes. A definition of population at risk for EDs has been established, that differentiates those with dieting criteria and those with binge-purge eating behaviour criteria. This definition includes a combination of weight, behaviour, Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria, and Eating Disorder Inventory (EDI) results. The General Health Questionnaire-28 (GHQ-28) was used to assess non-psychotic mental disorders. RESULTS: The prevalence of population at risk for EDs was 2.2% (95% CI: 1.6-2.8) for men and 15.3% (95% CI: 13.8-16.9) for women. The prevalence rate of combining both ED risk and mental disorder was 0.8% (95% CI: 0.4-1.2) for men and 9.9% (95% CI: 8.6-11.2) for women. Non-psychotic mental disorders were more prevalent in the population at risk for EDs than in the rest of the population. CONCLUSIONS: A considerable proportion of adolescent females have eating problems and non-psychotic mental disorders. Their male counterparts also suffer from these disorders, however, a different pattern is followed.

Adolescent↗

A compendium of gene expression in normal human tissues.

This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org) for future studies of pathophysiology.

Cluster Analysis↗

Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses.

We have generated a molecular taxonomy of lung carcinoma, the leading cause of cancer death in the United States and worldwide. Using oligonucleotide microarrays, we analyzed mRNA expression levels corresponding to 12,600 transcript sequences in 186 lung tumor samples, including 139 adenocarcinomas resected from the lung. Hierarchical and probabilistic clustering of expression data defined distinct subclasses of lung adenocarcinoma. Among these were tumors with high relative expression of neuroendocrine genes and of type II pneumocyte genes, respectively. Retrospective analysis revealed a less favorable outcome for the adenocarcinomas with neuroendocrine gene expression. The diagnostic potential of expression profiling is emphasized by its ability to discriminate primary lung adenocarcinomas from metastases of extra-pulmonary origin. These results suggest that integration of expression profile data with clinical parameters could aid in diagnosis of lung cancer patients.

Adenocarcinoma↗

Trends of HIV infection among injection drug users in Brazil in the 1990s: the impact of changes in patterns of drug use.

BACKGROUND: Santos Metropolitan Region (SMR), State of Sao Paulo, historically is well known as being one of the areas with the largest number of AIDS cases in Brazil, especially among injection drug users (IDUs). The main objective of this study was to assess the effects of changes in drug-using patterns among IDUs on trends in HIV infection among IDUs in the 1990s. METHODS: During 1991 through 1992 (wave 1; n = 214), 1994 through 1996 (wave 2; n = 135), and 1999 (wave 3; n = 108), we conducted three cross-sectional studies of IDUs. All participants were interviewed and tested for antibodies to HIV. FINDINGS: The overall sample population was 69% male, and 87% of the sample population was under 40 years old. Eighty-four percent of the population had less than 9 years of education. HIV seroprevalence was 63% in wave 1, 65% in wave 2, and 42% in wave 3 ( p <.001). Smoking of crack cocaine increased from 11% in wave 1 to 60% in wave 2 and 67% in wave 3 ( p <.001). The prevalence of frequent injections (>5 per day) decreased from 42% in wave 1 to 30% in wave 2 and 15% in wave 3 ( p <.001). INTERPRETATION: HIV prevalence decreased as injection frequency decreased and crack cocaine use increased. In SMR, patterns of drug use have been affecting the HIV epidemic more than scant public health intervention.

Adult↗

Harm reduction - a historical view from the left.

The harm reduction movement formed during a period in which social movements of the working class and the excluded were weak, neo-liberalism ideologically triumphant, and potential opposition movements were viewed as offering "tinkering" with the system rather than a total social alternative. This climate shaped and limited the perspectives, strategies, and tactics of harm reductionists almost everywhere. In many countries, this period was also marked by a "political economy of scapegoating" that often targeted drug users as the cause of social woes. This scapegoating took the form of "divide and rule" political initiatives by business and political leaderships to prevent social unrest in a long period of worldwide economic trends toward lowered profit rates and toward increasing income inequality. However, times have changed. Mass strikes and other labor struggles, opposition to the World Trade Organisation and other agencies of neo-liberalism, community-based protests against belt-tightening, and other forms of social unrest have been increasing in many countries. This opens up the possibility of new allies for the harm reduction movement, but also poses difficult problems for which we need to develop answers. On-the-ground experience in alliance formation needs to be combined with careful discussion of and research about what approaches work to convince other movements to work for and with harm reduction, and which approaches do not. Class differences within the harm reduction movement are likely to become more salient in terms of (a) creating internal tensions, (b) increasingly, opening up new ways in which working class harm reductionists can organize within their own communities and workplaces, and (c) producing different strategic orientations that will need to be discussed and debated. As a movement, we will need to find ways to accommodate and discuss differing perspectives, needs, and assessments of opportunities and threats without paralyzing harm reduction activities.

Journal Article↗

Transthoracic esophagectomy with radical mediastinal and abdominal lymph node dissection and cervical esophagogastrostomy for esophageal carcinoma.

BACKGROUND: Several techniques for esophageal resection have been reported. This study examines the morbidity, mortality, and early survival of patients after transthoracic esophagectomy for esophageal carcinoma using current staging techniques and neoadjuvant therapy. The technique includes right thoracotomy, laparotomy, and cervical esophagogastrostomy (total thoracic esophagectomy) with radical mediastinal and abdominal lymph node dissection. METHODS: Three hundred forty-two patients had surgery for esophageal carcinoma between 1989 and 2000 at our institution. Two hundred fifty consecutive patients had esophagectomy using this technique. Kaplan-Meier curves and univariate and multivariate analyses were performed by postsurgical pathologic stage. RESULTS: Median age was 62.7 years (31 to 86 years). Fifty-nine were female. Eighty-one percent (202) had induction chemotherapy (all patients with clinical T3/4 or N1). Early postoperative complications included recurrent laryngeal nerve injury (14% [35]), chylothorax (9%, [22]), and leak (8%, [19]). Median length of stay was 13 days (5 to 330 days). In-hospital or 30-day mortality was 3.6% (9). Overall survival at 3 years was 44%; median survival was 25 months, and 3-year survival by posttreatment pathologic stage was: stage 0 (complete response) (n = 60), 56%; stage I (n = 32), 65%; stage IIA (n = 67), 41%; stage IIB (n = 30), 46%; and stage III (n = 49), 17%. Mean follow-up was 24 months (SEM 1.6, 0 to 138 months). Five patients with tumor in situ, 6 patients with stage IV disease, and 1 patient who could not be staged (12 pts) were excluded from survival and multivariate calculations. In univariate and different models of multivariate analysis, age more than 65 years, posttreatment T3, and nodal involvement were predictive of poor survival. For univariate analysis, p = 0.002, p = 0.004, p = 0.02, respectively; for multivariate analysis, p = 0.001, p = 0.003, p = 0.02, respectively. CONCLUSIONS: Total thoracic esophagectomy with node dissection for esophageal cancer appears to have acceptable morbidity and mortality with encouraging survival results in the setting of neoadjuvant therapy. Patients who show complete response after induction chemoradiotherapy appear to have improved long-term survival.

Abdomen↗

Overdoses among cocaine users in Brazil.

AIMS: A survey of cocaine users was undertaken to study (i) the frequency of reported drug overdoses among cocaine users; and (ii) the frequency of witnessing drug overdoses in the same population. DESIGN AND SETTING: A cross-sectional study as part of the World Health Organization (WHO) Multi-city Study among injecting drug users (IDUs), phase II, was conducted in Santos Metropolitan Region, State of São Paulo, Brazil, in 1999. PARTICIPANTS: Three hundred and ninety-six exclusive users of cocaine in the Santos Metropolitan Region, São Paulo State, Brazil were surveyed concerning their past experience with drug overdoses. FINDINGS: Eighty (20%) of the cocaine users reported having experienced one or more overdoses, and 50% reported that they knew one or more other cocaine users who had died of an overdose. On multivariate analysis, being female and having spent time in jail were associated with an increased likelihood of having had one or more overdoses. CONCLUSION: Cocaine overdoses are an important and under-recognized health problem in the Santos Metropolitan Region, and possibly in other areas of Brazil.

Adolescent↗

Combined antegrade and retrograde dilation: a new endoscopic technique in the management of complex esophageal obstruction.

BACKGROUND: Esophageal strictures that cause complete obstruction are often difficult to dilate with standard bougienage techniques. METHODS: A new technique was developed and applied, combined antegrade and retrograde dilation, for dilatation of complex esophageal strictures. The stomach is accessed and an endoscope (9.8 mm diameter) is directed under fluoroscopy in a retrograde fashion into the distal esophagus. A guidewire with a hydrophilic coating is advanced through the stricture and then pulled through the mouth with a simultaneously placed proximal endoscope. The guidewire is then used as a guide for antegrade esophageal dilatation. RESULTS: Ten patients with complex esophageal strictures (with and without fistulas) were treated with this technique. Three required a second combined antegrade and retrograde dilation procedure. All strictures were dilated and no perforations occurred. CONCLUSIONS: Combined antegrade and retrograde dilation is a safe and effective technique for dilation of complex obstructing esophageal lesions.

Aged↗

The alpha folate receptor is highly activated in malignant pleural mesothelioma.

OBJECTIVE: To determine whether the folate receptor gene is overexpressed in malignant pleural mesothelioma. METHODS: Differential display analysis was performed with fresh frozen RNA obtained from normal lung, pleura, and mesothelioma. Sixty differentially expressed genes were identified and characterized. One gene that was over-expressed in mesothelioma versus normal tissue was the human alpha folate receptor. In situ hybridization with antisense probes designed on the basis of the sequence of the folate receptor was performed with frozen sections from 61 patients (33 epithelial and 28 mixed or sarcomatoid tumors) with malignant pleural mesothelioma. The controls included normal pleura, normal lung, other cancers, and sense controls for all of the tumors. Northern analysis with a folate receptor probe and immunohistochemical analysis with anti-alpha folate receptor antibodies were also performed. RESULTS: Forty-four (72%) of the 61 mesothelioma tumors were found to have between 2-fold and 4-fold higher mRNA expression of the folate receptor when compared with the control tissues. The histologic type of the tumor did not affect the rate of folate receptor activation. Northern analysis and immunohistochemical experiments confirmed these findings. CONCLUSIONS: A majority of mesothelioma tumors examined overexpress the alpha folate receptor protein when compared with normal adjacent tissues. This finding may help explain the observations that antifolate drugs have activity in the treatment of mesothelioma. It also encourages further study of folate receptor-related treatment strategies in this malignancy.

Carrier Proteins↗

Sequential thoracic metastasectomy prolongs survival by re-establishing local control within the chest.

OBJECTIVE: The value of sequential thoracic metastasectomies is unknown. We evaluate repeat metastasectomy for limited recurrences within the thorax. METHODS: From July 1988 to September 1998, 54 patients underwent 2 to 6 separate sequential procedures to excise metastases after recurrence isolated to the thorax. Kaplan-Meier survival and Cox modeling determined prognostic variables. RESULTS: Thirty-three men and 21 women, 22 to 76 years underwent 2 (100%, n = 54), 3 (50%), 4 (22%), or 5 to 6 (11%) metastasectomies. Fifty-four percent of patients had carcinoma, 35% sarcoma, 9% germ cell, and 2% melanoma. There were no operative deaths; all late deaths occurred from cancer. Median follow-up was 48 months. Cumulative 5-year survival from the second procedure was 57%. After the second, third, fourth, and fifth procedures, respectively, permanent control was achieved in 15 (27%) of 54 patients, 5 (19%) of 27, 1 (8%) of 12, and 0 of 7. Recurrence amenable to additional surgery occurred in 27 (50%) of 54, 12 (44%) of 27, 6 (50%) of 12, and 1 (17%) of 6. Mean hazard for the development of unresectable recurrence increased from 0.21 after the second procedure to 0.91 after the fifth procedure. The 5-year survival for the 27 patients undergoing only 2 metastasectomies was 60% (median not yet reached), 33% for the 15 patients undergoing only 3 metastasectomies (median 34.7 months), and 38% for the 12 patients undergoing 4 or more (median 45.6 months). From the time a recurrence was declared unresectable, patients had a 19% 2-year survival (median 8 months). CONCLUSIONS: Multiple attempts to re-establish intrathoracic control of metastatic disease is justified in carefully selected patients, but the magnitude of benefit decays with each subsequent attempt.

Adult↗

Rapidly responding to injecting drug use and HIV in Brazil: a field-report from São Vicente, São Paulo State.

As part of Phase II of the World Health Organisation (WHO) Injecting Drug Use Multi-City Study, Rapid Assessment and Response (RAR) methodology was used in São Vicente City (São Paulo State, Brazil) to analyse the situation regarding injecting drug use and HIV infection. Over a period of 8 weeks, analysis of existing information, focus groups (four) and depth interviews (45) were conducted, with qualitative data analysis taking a further 12 weeks. This work was undertaken by a team of six researchers (working mostly part-time on the project), and the research process was overseen by an Advisory Community Group. Key topics addressed included: the general drug use situation; HIV/AIDS and drugs; and harm reduction. Through the use of qualitative analysis it was found that there was: a negative moral status associated with drug use and drug users; prejudices against this group; and a lack of information about health services and HIV prevention programmes within São Vicente city. In regard to risk behavior, injecting drug users reported awareness of risks and methods of prevention. However, safer sex was considered difficult by all participants. Interventions were proposed by the research team to minimize problems and gaps in provision, and some of these have already occurred. A review of existing quantitative data found that some key institutions do not collect systematic data on drug use. Conclusions of the study include the need for interventions and the progress on Harm Reduction proposals and AIDS prevention among IDUs.

Journal Article↗

Nodal stage after induction therapy for stage IIIA lung cancer determines patient survival.

BACKGROUND: This study was undertaken to determine the predictive value of nodal status at resection in regards to long-term outcome of patients undergoing neoadjuvant therapy and resection for stage IIIA N2-positive non-small cell lung cancer (NSCLC). METHODS: We reviewed the medical records of all patients found on surgical staging to have N2-positive NSCLC and who underwent induction therapy followed by resection between 1988 and 1996 at our hospital. Complete follow-up information was examined utilizing Kaplan-Meier survival analysis and Cox proportional hazards multivariate analysis. RESULTS: One hundred three patients (59 men) with stage IIIA N2-positive NSCLC received neoadjuvant therapy before surgical resection. Preoperative therapy consisted of platinum-based chemotherapy (76), radiotherapy (18), or chemoradiation (9). Operations included pneumonectomy (38), bilobectomy (6), and lobectomy (59). There were four deaths and seven major complications. Eighty-five patients were followed until death. Median survival among 18 living patients is 60.9 months (range 29 to 121 months). Twenty-nine patients were downstaged to N0 and had 5-year survival of 35.8% (median survival 21.3 months). Seventy-four patients with persistent tumor in their lymph nodes (25 N1 and 49 N2) had significantly worse, 9%, 5-year survival, p = 0.023 (median survival 15.9 months). Other negative prognostic factors were adenocarcinoma and pneumonectomy. CONCLUSIONS: Patients with N2-positive NSCLC whose nodal disease is eradicated after neoadjuvant therapy and surgery enjoy significantly improved cancer-free survival. These data support surgical resection for patients downstaged by induction therapy; however, patients who are not downstaged do not benefit from surgical resection. Direct effort should be made to improve the accuracy of restaging before resection.

Adult↗

Surveillance transbronchial lung biopsies: implication for survival after lung transplantation.

OBJECTIVES: We wished to determine whether early rejection after lung transplantation as assessed by surveillance transbronchial biopsy predicts for survival. METHODS: Between 1990 and 1997, 96 consecutive patients had lung transplantation: 89 had a minimum 1-month follow-up. For 71 consecutive patients we have 1-year follow-up and for 69 patients we have the results of the first 3 biopsies. Cytomegalovirus status, bronchiolitis obliterans prevalence, and use of total lymphoid irradiation are noted. Biopsies were done at 1 week and 1, 3, and 6 months. Standard immunosuppression consisted of induction antilymphocyte globulin and high-dose methylprednisolone induction for 1 week and standard maintenance triple therapy. Acute rejection treatment was with pulse methylprednisolone. Bronchiolitis obliterans syndrome was treated with total lymphoid irradiation and a change to tacrolimus and mycophenolate. Blinded grading using International Society for Heart and Lung Transplantation classification was done retrospectively. RESULTS: Survival at 1 month and 1, 2, and 3 years for the 96-patient cohort with 1-year follow-up was 93%, 74%, 62%, and 56%. Survival was not significantly different for subsets with rejection on any combination of the first 3 biopsies (1/3, 2/3, 3/3) or absence of rejection on the first 3 biopsies. Ninety-one positive biopsy results were graded. Eighteen of 71 patients had one or more moderate or severe rejection episodes without survival difference relative to the others. There was no statistically significant association between acute rejection on the first 3 surveillance biopsy results and bronchiolitis obliterans. CONCLUSIONS: Intensive induction and maintenance immunotherapy with surveillance transbronchial biopsies and aggressive treatment of acute rejection is associated with a survival similar to that of patients without early acute rejection. This regimen appears to uncouple the association between early acute rejection and bronchiolitis obliterans. Further study may elucidate this mechanism.

Adolescent↗

Pretreatment staging by endoscopic ultrasonography does not predict complete response to neoadjuvant chemoradiation in patients with esophageal carcinoma.

BACKGROUND: Endoscopic ultrasonography (EUS) provides highly accurate preoperative T and N classifications in patients with esophageal carcinoma. Although previous data have suggested that patients with tumors classified as T4 by EUS do not benefit from surgical resection, these data were acquired prior to the widespread use of preoperative chemoradiation. The current study investigated whether pretreatment EUS can predict a complete response to neoadjuvant therapy. METHODS: Patients with esophageal carcinoma (adenocarcinoma or squamous cell carcinoma) underwent EUS classification prior to therapy. Patients classified as T2, T3, or T4 and M0 were treated with 5-fluorouracil, cisplatin, and radiation under protocol. Patients with T1 lesions underwent resection without prior chemoradiation. Chemoradiation was followed in all cases by attempted surgical resection. The initial EUS classification was compared with the final pathologic results. RESULTS: Fifty-five patients (47 males and 8 females) with a mean age of 60.5 years (range, 31-78 years) were evaluated. There were 41 adenocarcinomas and 14 squamous cell carcinomas. Among the total population, a complete response was achieved in 3 of 5 patients (60%) with tumors classified as T2 by EUS, 14 of 42 patients (33%) with tumors classified as T3 by EUS, and 5 of 8 patients (63%) with tumors classified as T4 by EUS (P = 0.19). A complete response was achieved in 9 of 24 patients (38%) found to have N0 disease by EUS versus 13 of 30 patients (43%) determined to have N1 disease (P = 0.66). The results for patients with adenocarcinoma and squamous cell carcinoma were similar. CONCLUSIONS: The results of the current study demonstrate that pretreatment EUS does not predict reliably which patients with esophageal carcinoma will achieve a complete pathologic response to preoperative neoadjuvant chemoradiation.

Adenocarcinoma↗

Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients.

OBJECTIVES: Our aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma. METHODS: From 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy. RESULTS: Forty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P =.0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P =.02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P =.004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P <.0001), positive resection margins (OR 1.7, CI 1.2-2.6; P =.0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2; P =.0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P =.013). A previously published staging system using these variables stratified survival (P <.05). CONCLUSIONS: (1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival.

Adult↗