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A anemia falciforme, expressão clínica dos homozigotos do gene da hemoglobina S, é a doença hereditária mais freqüente no Brasil. Apesar disso, a metodologia genético-epidemiológica raramente é usada nos estudos brasileiros sobre essa alteração. No presente estudo foram analisados, por meio de um software específico, os dados de 817 heterozigotos do gene da HbS (513 homens e 304 mulheres), não consangüíneos, com idades entre 18 e 65 anos, detectados voluntariamente na cidade de Campinas, SP, Sudeste do Brasil. A constituição genômica caucasóide, negróide e indígena foi avaliada na amostra de portadores da hemoglobina S através do estudo das freqüências alélicas do sistema sangüíneo ABO e comparada com a observada na população geral da mesma cidade. A análise dos dados demonstrou que 52% dos portadores da HbS tiveram sua ancestralidade africana evidenciada pelo seu fenótipo e que 36% dos indivíduos eram procedentes do Nordeste do Brasil, sobretudo da Bahia (15%). Essa imigração interna tende a diminuir a proporção do haplótipo Bantu da hemoglobina S (mais grave) na região de Campinas, aumentando a proporção do haplótipo Benin (mais benigno). A amostra possui um componente gênico negróide de 45%, caucasóide de 41%, e indígena de 14%. Essa composição genômica é significativamente diferente da observada na população geral da mesma cidade, apresentando uma participação gênica maior de negróides e de indígenas (influência da imigração nordestina) e menor de caucasóides. A imigração nordestina e a miscigenação alteraram significativamente o perfil genético-epidemiológico dos portadores da hemoglobina S na região de Campinas, SP.Sickle cell anemia, the clinical expression of individuals homozygous for the hemoglobin S gene, is the most frequent hereditary disease in Brazil. Nevertheless, a genetic-epidemiological approach is rarely used in Brazilian studies related to this alteration. In the present study, using a specific computer program, data from 817 (513 males and 304 females) non-consanguineous individuals heterozygous for the hemoglobin S gene were studied. The participants, with ages varying from 18 to 65 years old, live from the region of Campinas, Southeastern Brazil. The Caucasoid, Negroid and native Indian genomic backgrounds of this sample were evaluated by a study of allelic frequencies for the ABO blood group system and compared with those observed in the general population from the same city. Data analysis showed that: 52% of the hemoglobin S carriers had African ancestry as shown by their phenotypes and that 36% of the subjects came from North-eastern Brazil, most from the state of Bahia (15%). This internal migration tends to decrease the proportion of the hemoglobin S Bantu (wild) haplotype in the region of Campinas, by increasing the proportion of the Benin haplotype (milder). The frequencies of this sample were Negroes 45%, Caucasians 41%, and native Indians 14%. This genomic constitution is significantly different from that observed in the general population from the same city with greater frequencies of Negroes and native Indians and a lower frequency of Caucasians. Migration from the northeastern and miscegenation have significantly altered the genetic-epidemiological profile of hemoglobin S carriers in the region of Campinas.

PURPOSE: To evaluate a new method designed for estimating the tumor extent in radical prostatectomy specimens. The tumor extent was correlated to preoperative PSA and to several pathologic findings in the surgical specimens as well. MATERIALS AND METHODS: Tumor extent was estimated in 118 consecutive radical prostatectomies through a simple point-count method. Drawn on a sheet of paper, each quadrant of the whole mount sections contained 8 equidistant points. During the microscopic slides examination, the tumor area was drawn over the correspondent quadrant of the paper sheet. According to the extent, tumors were classified in 5 groups: 1) very limited: £ 10 positive points; 2) limited: 11-19 positive points; 3) moderately extensive: 20-35 positive points; 4) extensive: 36-39 positive points; 5) very extensive: 70 positive points. This classification was based on a previous analysis of tumor extent in 109 radical prostatectomies. The distribution was quite normal up to 69 positive points, but asymmetric above that number, including cases exceeding far above that value. We considered the quartiles of the normal distribution up to 69 positive points (groups 1 to 4), and above that value a fifth group was considered. RESULTS: There was a statistically significant and direct correlation between the tumor extent and all variables studied: preoperative PSA (p = 0.03), Gleason score (p < 0.0001), primary grade in high-grade tumors (p < 0.01), surgical margins (p < 0.0001), extraprostatic extension (pT3a) (p < 0.0001), and seminal vesicle invasion (pT3b) (p = 0.01). CONCLUSIONS: The method, which is simple and well correlated to other prognostic factors, is accessible to those pathologists working in routine pathology laboratories. Whether this method will be used by other urology centers is yet to be seen.

A Portaria do Ministério da Saúde n.º 822/01 regulamentou a triagem neonatal de vários distúrbios metabólicos, incluindo as doenças falciformes e outras hemoglobinopatias. No presente trabalho, os autores comentam vários aspectos médicos e éticos da triagem neonatal das hemoglobinopatias, o aconselhamento genético como parte da responsabilidade médica e os riscos inerentes aos programas populacionais, que merecem ser conhecidos e prevenidos pelos profissionais que atuam na área de triagem neonatal.

Between 1992 and 1997, 790 blood donors with anti-HCV EIA-2 strongly reagent (relationship between the sample optical density/cut-off > 3) detected at the blood bank serological screening, were evaluated in ambulatory environment. They were all negative for Chagas disease, syphilis, hepatitis B (HBsAg) and AIDS. Blood samples were collected at the first ambulatorial evaluation, for hemogram, biochemical tests and new serological tests for HCV (anti-HCV EIA-2). In blood samples of 226 repeatedly reagent anti-HCV EIA-2 blood donors, supplementary "immunoblot" test for HCV (RIBA-2) was used. In 209 donors, the presence of HCV-RNA was investigated by the PCR test. The abdominal ultrasonography was realized in 366 donors. In 269 patients liver biopsy was performed for the histopathological study. The follow-up of blood donors showed that 95.6% were repeatedly EIA-2 reagent, 94% were symptomless and denied any hepatitis history, with only 2% mentioning previous jaundice. In 47% of this population at least one risk factor has been detected for the HCV transmission, the use of intravenous drugs being the main one (27.8%). Blood transfusion was the second factor for HCV transmission (27.2%). Hepatomegaly was detected in 54% of the cases. Splenomegaly and signs of portal hypertension have seldom been found in the physical examination, indicating a low degree of hepatic compromising in HCV. Abdominal ultrasound showed alterations in 65% of the subjects, being the steatosis the most frequent (50%). In 83.5% of the donors submitted to the liver biopsy, the histopathological exam showed the presence of chronic hepatitis, usually classified as active (89%) with mild or moderate grade in most of the cases (99.5%). The histopathological exam of the liver was normal in 1.5% of blood donors. The RIBA-2 test and the HCV-RNA investigation by PCR were positive in respectively 91.6 and 75% of the anti-HCV EIA-2 reagent donors. The HCV-RNA research was positive in 82% of the RIBA-2 positive subjects, in 37.5% of the indeterminate RIBA-2 donors and in 9% of the negative RIBA-2 donors. Chronic hepatitis has also been observed in 50% of the histopathological exams of the anti-HCV EIA-2 reagent donors which were indeterminate RIBA-2. Among 18 blood donors with minimal changes histopathological exam 11 (61%) were HCV-RNA positive. Our blood donors anti-HCV reagent generally had clinical, laboratorial and histopathological features observed in patients with chronic HCV hepatitis and a high proportion could be identified in interviews and medical evaluation realized in blood blanks. Generally, these HCV infected donors are identified and discharged only by the serological tests results.Entre 1992 e 1997 foram avaliados, ambulatorialmente, 790 doadores de sangue com teste anti-HCV EIA-2 fortemente reagente (relação entre a densidade ótica da amostra / "cut-off" > 3), que haviam sido detectados na triagem sorológica do banco de sangue. Todos eram negativos para doença de Chagas, sífilis, hepatite B (HBsAg) e AIDS. Amostras de sangue foram coletadas, na primeira consulta ambulatorial, para a realização de hemograma, exames bioquímicos e novos testes sorológicos para a HVC (anti-HCV EIA-2). Em 226 doadores anti-HCV EIA-2 repetidamente reagentes, realizou-se o teste suplementar de "immunoblot" para a HVC (RIBA-2). Em 209 doadores, pesquisou-se a presença do RNA do VHC pelo teste do PCR, através de exame automatizado (HCV-AMPLICOR, ROCHE). A ultra-sonografia abdominal foi realizada em 366 doadores e a biópsia hepática em 269 concordantes. Notou-se que 95,6% eram EIA-2 repetidamente reagentes, 94% eram assintomáticos e que apenas 2% referiram icterícia pregressa. Em 47% detectou-se, pelo menos, um fator de risco para a transmissão do VHC, sendo o uso de drogas E.V. o principal deles (27,8%). A transfusão de sangue foi o segundo fator na transmissão da HVC (27,2%). Hepatomegalia foi encontrada em 54%. Esplenomegalia e sinais de hipertensão portal foram raramente encontrados no exame físico, denotando o baixo grau de comprometimento hepático na HVC. A ultra-sonografia abdominal mostrou-se alterada em 65% dos indivíduos, sendo a esteatose a alteração mais freqüentemente observada (50%). Em 83,5% dos doadores submetidos à biópsia hepática, diagnosticou-se hepatite crônica, geralmente classificada como ativa (89%) e de grau leve ou moderado na maioria dos casos (99,5%). O histopatológico foi normal em 1,5% dos doadores. O teste de RIBA-2 e a pesquisa do RNA do VHC pelo PCR foram positivos em, respectivamente, 91,6 e 75% dos doadores anti-HCV EIA-2 reagentes. A pesquisa do RNA do VHC foi positiva em 82% dos indivíduos RIBA-2 reagentes, em 37,5% dos doadores RIBA-2 indeterminados e em 9% dos RIBA-2 negativos. Hepatite crônica foi observada em 50% dos doadores RIBA-2 indeterminados. Entre 18 doadores com alterações mínimas, ao exame histopatológico, 11 (61%) eram positivos para o RNA do VHC. Nossos doadores de sangue anti-HCV reagentes geralmente apresentam alterações clínicas, laboratoriais e histopatológicas próprias de pacientes com hepatites crônicas pelo VHC e uma elevada proporção destes podem ser identificados em entrevistas e avaliação médicas rotineiramente realizadas em bancos de sangue. Geralmente estes doadores infectados pelo VHC somente são identificados e bloqueados pelos resultados dos testes sorológicos.

Nós efetuamos determinações da série vermelha, dosagem da sulfonemia, dosagem de metemoglobina, contagem de reticulócitos e dosagem da atividade enzimática da NADHdiaforase no hemolisado e nas membranas dos eritrócitos livres de hemoglobina em 72 pacientes portadores de hanseníase, todos ingerindo doses diárias de 100 mg de diaminodifenil-sulfona. Idênticos testes, exceto dosagem de sulfona, foram efetuados no sangue de 72 pessoas normais, não ingerindo medicamentos oxidantes. Foram encontradas diferenças estatísticas significativas nas variáveis da série vermelha, metemoglobina, reticulócitos e na atividade enzimática da NADH-redutase nas membranas eritrocitárias entre os dois grupos. A atividade enzimática nas membranas eritrocitárias foi inferior e estatisticamente significativa com relação ao grupo-controle. A atividade enzimática da NADH-redutase no hemolisado não apresentou diferença estatística significativa quando feita a correção pela taxa de hemoglobina. O nível de metemoglobina foi superior nos portadores de hanseníase em relação ao grupocontrole, provavelmente devido à ação oxidante da sulfona. Tendo em vista termos encontrado níveis inferiores de atividade enzimática nas membranas eritrocitárias dos hansenianos e níveis coincidentes no hemolisado, em comparação com um grupo-controle, podemos afirmar que, provavelmente, isto se deve ao deslocamento enzimático da membrana celular para o citoplasma, com o objetivo de manter o eritrócito em equilíbrio hemoglobínico constante, apesar da ação oxidante da sulfona.

Purpose To analyze the correlations between age-related macular degeneration (AMD) and genetic and environmental risk factors for in a Brazilian population. Design Cross-sectional study with a control group. Methods We collected data on 236 participants 50 years of age or older (141 with AMD and 95 controls without the disease). Data was obtained using a questionnaire and included information on demographics, ocular and medical history, family history of AMD, lifestyle, and smoking and drinking habits. Genetic evaluations included direct sequencing for the LOC387715 (rs10490924) variant, as well as PCR and enzymatic digestion for the CFH Y402H (rs1061170) and HTRA1 (rs11200638) variants. We performed a risk assessment of environmental risk factors and genetic variants associated with AMD and determined correlations between AMD and the data collected using multiple linear regression analysis. Results Of the 141 AMD cases, 99 (70%) had advanced AMD in at least one eye (57% neovascular AMD and 13% geographic atrophy), and 42 (30%) had not-advanced AMD. Family history of AMD (OR: 6.58; 95% CI: 1.94–22.31), presence of cardiovascular disease (CVD) (OR: 2.39; 95% CI: 1.08–5.28), low physical activity level (OR: 1.39; 95% CI: 0.82–2.37), and high serum cholesterol (OR: 1.49; 95% CI: 0.84–2.65) were associated with an increased risk for AMD. There was a significant association between CVD and incidence of advanced AMD (OR: 2.29; 95% CI 0.81–6.44). The OR for the risk allele of the LOC387715 gene, the CFH gene and the HTRA1 gene were 2.21 (95% CI: 1.47–3.35), 2.27 (95% CI: 1.52–3.37), and 2.76 (95% CI: 1.89–4.03), respectively. In the stepwise multiple linear regression analyses, the HTRA1 and CFH risk alleles, family history of AMD, the LOC387715 risk allele, and CVD were associated with an increased risk of AMD for a total of 25.6% contribution to the AMD phenotype. Conclusions The analysis correlating environmental and genetic risk factors such as family history of AMD, and CVD and the variants of HTRA1, CFH, and LOC387715 genes showed an expressive contribution for the development of AMD among this admixed population.

Purpose To analyze controversial clinicopathologic predictors of biochemical recurrence after surgery: age, race, tumor extent on surgical specimen, tumor extent on needle biopsy, Gleason score 3 + 4 vs 4 + 3, and amount of extent of extraprostatic extension and positive surgical margins. Materials and Methods The needle biopsies and the correspondent surgical specimens were analyzed from 400 patients. Time to recurrence was analyzed with the Kaplan-Meier curves and risk of shorter time to recurrence using Cox univariate and multivariate analysis. Results Except for age, race, maximum percentage of cancer per core, and number of cores with cancer, all other variables studied were significantly predictive of time to biochemical recurrence using the Kaplan-Meier curves. In univariate analysis, except for focal extraprostatic extension, age, race, focal positive surgical margins, and maximum extent and percentage of cancer per core, all other variables were significantly predictive of shorter time to recurrence. On multivariate analysis, diffuse positive surgical margins and preoperative PSA were independent predictors. Conclusions Young patients and non-whites were not significantly associated with time to biochemical recurrence. The time consuming tumor extent evaluation in surgical specimens seems not to add additional information to other well established predictive findings. The higher predictive value of Gleason score 4 + 3 = 7 vs 3 + 4 = 7 discloses the importance of grade 4 as the predominant pattern. Extent and not simply presence or absent of extraprostatic extension should be informed. Most tumor extent evaluations on needle biopsies are predictive of time to biochemical recurrence, however, maximum percentage of cancer in all cores was the strongest predictor.

Objective There is evidence that reactive stroma in different cancers may regulate tumor progression. The aim of this study is to establish any possible relation of reactive stroma grading on needle prostatic biopsies to biochemical recurrence. Materials and Methods The study group comprised 266 biopsies from consecutive patients submitted to radical prostatectomy. Reactive stroma was defined as stroma surrounding neoplastic tissue and graded as 0 (absent), 1 (slight), 2 (moderate), and 3 (intense) according to tumor stroma area relative to total tumor area. Results From the total of 266 needle prostatic biopsies, 143 (53.8%), 55 (20.7%), 54 (20.3%), and 14 (5.3%) showed grades 0, 1, 2, and 3, respectively. Increasing reactive stroma grade was significantly associated with clinical stage T2, higher preoperative PSA, higher biopsy and radical prostatectomy Gleason score, more extensive tumors in radical prostatectomy, and pathologic stage > T2. Only grade 3 was significantly associated with time and risk to biochemical recurrence. On multivariate analysis only preoperative PSA and 2 methods of biopsy tumor extent evaluation were independent predictors. Conclusion Increasing reactive stroma grade on biopsies is significantly associated with several clinicopathologic adverse findings, however, only grade 3 predicts time and risk to biochemical recurrence following radical prostatectomy on univariate but not on multivariate analysis. We have not been able to show that reactive stroma grade 3 on biopsies is an independent predictor of biochemical recurrence beyond that of preoperative PSA and other pathologic findings on biopsy.

PURPOSE: The amount of extraprostatic extension and positive surgical margin correlates in most studies with biochemical recurrence following radical prostatectomy. We studied the influence of focal and diffuse extraprostatic extension and positive surgical margins on biochemical progression using a simple method for quantification. MATERIALS AND METHODS: A total of 360 prostates were step-sectioned and totally processed from 175 patients with stage T1c and 185 patients with clinical stage T2 submitted to radical retropubic prostatectomy. Extraprostatic extension was stratified into 2 groups: present up to 1 quadrant and/or section from the bladder neck or apex (Group 1, focal) and in more than 1 quadrant or section (Group 2, diffuse); and, positive surgical margin present up to 2 quadrants and/or sections (Group 1, focal) and in more than 2 quadrants or sections (Group 2, diffuse). The Kaplan-Meier product-limit analysis was used for the time to biochemical recurrence, and an univariate and multivariate Cox stepwise logistic regression model to identify significant predictors. RESULTS: Extraprostatic extension was found in 129/360 (35.8%) patients, 39/129 (30.2%) in Group 1 and 90/129 (69.8%) in Group 2. In univariate analysis but not in multivariate analysis, patients showing diffuse extraprostatic extension (Group 2) had a significant higher risk to develop biochemical recurrence in a shorter time. Positive surgical margin was present in 160/360 (44.4%) patients, 81/160 (50.6%) patients in Group 1 and 79/160 (49.4%) patients in Group 2. Patients with diffuse positive surgical margins (Group 2) had a significant higher risk in both univariate and multivariate analyses. Diffuse positive surgical margin was the strongest predictor on both analyses and an independent predictor on multivariate analysis. CONCLUSION: Diffuse extraprostatic extension in univariate analysis and positive surgical margins on both univariate and multivariate analyses are significant predictors of shorter time to biochemical progression following radical prostatectomy.

PURPOSE: Perineural invasion (PNI) on needle prostatic biopsies (NPB) has been controversial as a marker of extraprostatic extension and consequently for planning of nerve-sparing radical prostatectomy (RP). The aim of this study was to find whether tumor extent on NPB influences the value of PNI to predict stage > pT2 on RP. MATERIALS AND METHODS: This retrospective study was based on 264 consecutive patients submitted to radical retropubic prostatectomy. Their NPB were matched with whole-mount processed and totally embedded surgical specimens. Tumor extent on NPB was evaluated as the percentage of linear tissue in mm containing carcinoma in all cores. Considering the median value, patients were stratified into 2 groups: harboring less or more extensive tumors on NPB. Univariate and multivariate logistic regression analyses were used to relate stage > pT2 to PNI and other clinical and pathological variables. RESULTS: In patients with more extensive tumors, PNI was predictive of stage > pT2 in univariate analysis but not in multivariate analysis. In less extensive tumors, PNI showed no association between any clinical or pathological variables studied; no difference in the time to biochemical progression-free status compared to patients without PNI; and, no predictive value for pathological stage > pT2 on both univariate and multivariate analyses. CONCLUSION: Tumor extent on NPB influences the predictive value of PNI for pathologic stage > pT2 on RP. With a higher number of small tumors currently detected, there is no evidence that perineural invasion should influence the decision on preservation of the nerve during radical prostatectomy.

OBJECTIVE: There is evidence showing that Gleason grading of prostatic adenocarcinoma is one of the most powerful predictors of biological behavior and one of the most influential factors used to determine treatment for prostate cancer. The aim of the current study was to compare the Gleason score for needle biopsy to the Gleason score for the correspondent surgical specimen, find any possible difference in the biochemical (PSA) progression following surgery in upgraded cases, correlate Gleason score in the specimens to several clinicopathologic variables, and compare outcomes between patients with low-grade vs. high-grade Gleason and Gleason scores 3+4 vs. 4+3. MATERIALS AND METHODS: The study population consisted of 200 consecutive patients submitted to radical prostatectomy. Biochemical progression was defined as PSA > 0.2 ng/mL. Time to PSA progression was studied using the Kaplan-Meier product-limit analysis. RESULTS: In 47.1% of the cases, there was an exact correlation and 40.6% of cases were underestimated in the biopsies. Half of the tumors graded Gleason 6 at biopsy were Gleason score 7 at surgery. These upgraded tumors had outcomes similar to tumors with Gleason score 7 in both biopsy and surgery. There was a positive correlation of high-grade Gleason score in the surgical specimens to higher preoperative PSA, more extensive tumors, positive margins and more advanced pathologic staging. Tumors with a Gleason score > 7 have lower PSA progression-free survival vs. Gleason scores < 7. In this series, there was no significant difference when comparing Gleason scores of 3+4 vs. 4+3. CONCLUSIONS: The findings support the importance of Gleason grading for nomograms, which are used by clinicians to counsel individual patients and help them make important decisions regarding their disease.

INTRODUCTION: Chronic inflammation of longstanding duration has been linked to the development of carcinoma in several organ systems. It is controversial whether there is any relationship of inflammatory atrophy to prostate cancer. It has been suggested that the proliferative epithelium in inflammatory atrophy may progress to high-grade prostatic intraepithelial neoplasia and/or adenocarcinoma. The objective of our study is to compare on needle prostate biopsies of patients showing cancer the topographical relation of inflammatory atrophy and atrophy with no inflammation to adenocarcinoma. MATERIALS AND METHODS: The frequency and extent of the lesions were studied on 172 needle biopsies of patients with prostate cancer. In cores showing both lesions, the foci of atrophy were counted. Clinicopathological features were compared according to presence or absence of inflammation. RESULTS: Considering only cores showing adenocarcinoma, atrophy was seen in 116/172 (67.44%) biopsies; 70/116 (60.34%) biopsies showed atrophy and no inflammation and 46/116 (39.66%) biopsies showed inflammatory atrophy. From a total of 481 cores in 72 biopsies with inflammatory atrophy 184/481 (38.25%) cores showed no atrophy; 166/481 (34.51%) cores showed atrophy and no inflammation; 111/481 (23.08%) cores showed both lesions; and 20/481 (4.16%) showed only inflammatory atrophy. There was no statistically significant difference for the clinicopathological features studied. CONCLUSION: The result of our study seems not to favor the model of prostatic carcinogenesis in which there is a topographical relation of inflammatory atrophy to adenocarcinoma.

PURPOSE: A recent study has found that PSA recurrence rate for clinical T1c tumors is similar to T2 tumors, indicating a need for further refinement of clinical staging system. To test this finding we compared clinicopathologic characteristics and the time to PSA progression following radical retropubic prostatectomy of patients with clinical stage T1c tumors to those with stage T2, T2a or T2b tumors. MATERIALS AND METHODS: From a total of 186 consecutive patients submitted to prostatectomy, 33.52% had clinical stage T1c tumors, 45.45% stage T2a tumors and 21.02% stage T2b tumors. The variables studied were age, preoperative PSA, prostate weight, Gleason score, tumor extent, positive surgical margins, extraprostatic extension (pT3a), seminal vesicle invasion (pT3b), and time to PSA progression. Tumor extent was evaluated by a point-count method. RESULTS: Patients with clinical stage T1c were younger and had the lowest mean preoperative PSA. In the surgical specimen, they had higher frequency of Gleason score < 7 and more organ confined cancer. In 40.54% of the patients with clinical stage T2b tumors, there was extraprostatic extension (pT3a). During the study period, 54 patients (30.68%) developed a biochemical progression. Kaplan-Meier product-limit analysis revealed no significant difference in the time to PSA progression between men with clinical stage T1c versus clinical stage T2 (p = 0.7959), T2a (p = 0.6060) or T2b (p = 0.2941) as well as between men with clinical stage T2a versus stage T2b (p = 0.0994). CONCLUSION: Clinicopathological features are not similar considering clinical stage T1c versus clinical stages T2, T2a or T2b.

OBJECTIVE: In the 1997 TNM staging system, tumors were classified into a single subdivision: T2a, and bilateral tumor involvement (T2b). In the 2002 TNM staging system, tumors are subclassified as T2a (less than one half of one lobe involvement), T2b (more than one half of one lobe involvement), and T2c (bilateral involvement). A recent study questioned the existence of a true pathologic pT2b tumor. The aim of our study is to verify this question. MATERIALS AND METHODS: The study population consisted of 224 men submitted to radical retropubic prostatectomy. The surgical specimens were histologically evaluated by complete embedding and whole-mount processing. Tumor extent was evaluated by a point-count method. The surgical specimens were staged according to the 2002 TNM staging system. RESULTS: Using the 2002 TNM criteria, the surgical specimens were classified as pT2a, 28 (12.50%); pT2b, 0 (0%); pT2c, 138 (61.61%); pT3a, 30 (13.39%); and, pT3b, 28 (12.50%). Using the point-count method for tumor extent evaluation, the minimum and maximum total points obtained in unilateral tumors were 192 and 368 points, respectively; the most extensive unilateral tumor showed 68 positive points (less than half the minimum total point-count). CONCLUSIONS: Using the point-count method for tumor extent, our study questions a real existence for pathologic stage pT2b tumors (unilateral tumors involving greater than one-half of one lobe).

OBJECTIVE: It is controversial whether age is associated with higher grade and worse outcome. Some studies have not found age to be related to outcome nor younger age to be associated with better response to therapy. MATERIALS AND METHODS: The study population consisted of 27 patients aged 55 years or younger and 173 patients 56 years or older submitted to radical prostatectomy. The variables studied were preoperative PSA, time to PSA progression following radical prostatectomy and pathologic findings in surgical specimens: Gleason score, Gleason predominant grade, positive surgical margins, tumor extent, extraprostatic extension (pT3a), and seminal vesicle invasion (pT3b). RESULTS: Comparing patients aged 55 years or younger and 56 years or older, there was no statistically significant difference for all variables studied: preoperative PSA (p = 0.4417), Gleason score (p = 0.3934), Gleason predominant grade (p = 0.2653), tumor extent (p = 0.1190), positive surgical margins (p = 0.8335), extraprostatic extension (p = 0.3447) and seminal vesicle invasion (p > 0.9999). During the study period, 44 patients (22%) developed PSA progression. No difference was found in the time to biochemical progression between men aged 55 years or younger and 56 years or older. CONCLUSION: Our findings suggest that age alone do not influence the biological aggressiveness of prostate cancer.

ABSTRACT Purpose To find any influence on prognostic factors of index tumor according to predominant location. Materials and Methods Prostate surgical specimens from 499 patients submitted to radical retropubic prostatectomy were step-sectioned. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semi-quantitative point-count method. The index tumor (dominant nodule) was recorded as the maximal number of positive points of the most extensive tumor area from the quadrants and the predominant location was considered anterior (anterolateral quadrants), posterior (posterolateral quadrants), basal (quadrants in upper half of the prostate), apical (quadrants in lower half of the prostate), left (left quadrants) or right (right quadrants). Time to biochemical recurrence was analyzed by Kaplan-Meier product-limit analysis and prediction of shorter time to biochemical recurrence using univariate and multivariate Cox proportional hazards model. Results Index tumors with predominant posterior location were significantly associated with higher total tumor extent, needle and radical prostatectomy Gleason score, positive lymph nodes and preoperative prostate-specific antigen. Index tumors with predominant basal location were significantly associated with higher preoperative prostate-specific antigen, pathological stage higher than pT2, extra-prostatic extension, and seminal vesicle invasion. Index tumors with predominant basal location were significantly associated with time to biochemical recurrence in Kaplan-Meier estimates and significantly predicted shorter time to biochemical recurrence on univariate analysis but not on multivariate analysis. Conclusions The study suggests that index tumor predominant location is associated with prognosis in radical prostatectomies, however, in multivariate analysis do not offer advantage over other well-established prognostic factors.

ABSTRACT Purpose: The 8th edition of the TNM has been updated and improved in order to ensure a high degree of clinical relevance. A major change in prostate includes pathologically organ - confined disease to be considered pT2 and no longer subclassified by extent of involvement or laterality. The aim of this study was to validate this major change. Materials and Methods: Prostates were step - sectioned from 196 patients submitted to radical prostatectomy with organ confined disease (pT2) and negative surgical margins. Tumor extent was evaluated by a semiquantitative point count method. The dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer from the quadrants. Laterality was considered as either total tumor extent (Group 1) or index tumor extent (Group 2). Time to biochemical recurrence was analyzed with the Kaplan - Meier product limit analysis and prediction of shorter time to biochemical recurrence with Cox proportional hazards model. Results: In Group 1, 43 / 196 (21.9%) tumors were unilateral and 153 / 196 (78.1%) bilateral and in Group 2, 156 / 196 (79.6%) tumors were unilateral and 40 / 196 (20.4%) bilateral. In both groups, comparing unilateral vs bilateral tumors, there was no significant clinicopathological difference, and no significant association with time as well as prediction of shorter time to biochemical recurrence following surgery. Conclusions: Pathologic sub - staging of organ confined disease does not convey prognostic information either considering laterality as total tumor extent or index tumor extent. Furthermore, no correlation exists between digital rectal examination and pathologic stage.

Objetivo: Os procedimentos conservadores sobre a valva mitral têm vantagens sobre a troca da mesma. Avaliamos os resultados a médio prazo em pacientes com valvopatia mitral de causa reumática quanto às variáveis clínicas e ecocardiográficas. Casuística e Métodos: Cinqüenta e seis pacientes foram submetidos a procedimentos conservadores sobre a valva mitral de etiologia reumática. Quarenta e seis (82,1%) pacientes eram do sexo feminino e 10 (17,9%) do sexo masculino. A idade média dos pacientes foi de 34,70 anos (desvio padrão 13,88 anos). O tempo médio de seguimento foi de 23,84 meses (desvio padrão 9,23 anos). Vinte e cinco (44,6%) pacientes estavam em classe funcional III ou IV e 11 (19,6%) pacientes apresentavam fibrilação atrial antes da cirurgia. Os procedimentos realizados foram comissurotomia com papilaromiotomia em 11 (19,6%) pacientes, comissurotomia com anuloplastia utilizando órtese maleável de pericárdio bovino em 27 (48,2%) pacientes e anuloplastia com órtese maleável de pericárdio bovino em 18 (32,1%) pacientes. Resultados: Houve um óbito (1,7%) per-operatório (30 dias) no grupo estudado. Um paciente apresentou acidente vascular transitório no período pós-operatório, com total recuperação. Ocorreu melhora quanto ao volume diastólico final do ventrículo esquerdo de 52,0 ± 12,4 mm para 48,8 ± 9,9 (p = 0,001), tamanho do átrio esquerdo de 53,0 ± 8,0 mm para 47,8 ± 7,6 mm (p < 0,0001). Ocorreu melhora significativa quanto à classe funcional (p = 0,0001), ficando apenas 1 (1,8%) paciente em classe III. Ocorreram duas reoperações com 28,5 meses e 2,93 meses de seguimento; ficaram livres de reoperação 96,43% no tempo de seguimento. Conclusão: Concluímos que o reparo da valva mitral a médio prazo proporciona bons resultados, com melhora de parâmetros ecocardiográficos e clínicos.Objective: Conservative procedures on the valve mitral have advantages over its replacement. We evaluated the mid term results in patients with rheumatic mitral disease regarding clinical and echocardiography variables. Material and Methods: Fifty six patients with rheumatic etiology were submitted to mitral valve repair. Forty six patients were female (82.1%) and ten male (17.9%). The average age was 34.70 years (standard deviation 13.88 years). Average time of follow-up was 23.84 months (standard deviation 9.23 years). Twenty five patients (44.6%) were in functional class III or IV and eleven patients with atrial fibrillation (19.6%) before surgery. The procedures were commissurotomy, commissurotomy with papillaromyotomy in 11 patient (19.6%), commissurotomy with malleable annuloplasty bovine pericardium prosthesis in 27 patients (48.2%) and malleable annuloplasty bovine pericardium prosthesis in 18 patients (32.1%). Results: There was one death (30 days) in this series (1.7%). One patient presented transitory vascular accident in the operative period with total recovery. Improvement ocurred with regard to the final diastolic volume of the left ventricule from 52.0 ± 12.4 mm to 48.8 ± 9.9 (p = 0.001), left atrium size from 53.0 ± 8.0 mm to 47.8 ± 7.6 mm (p < 0.0001). Functional class improved significantly (p = 0.0001), with just one patient in class III (1.8%). It happened two reoperations with 28.5 months and 2.93 months of follow-up, 96.43% were free reoperation in the follow-up period. Conclusion: We conclude that mitral valve repair over the mid term provides good results with improvement of echocardiography and clinical parameters.

OBJETIVO: O trauma é um problema de saúde pública de enormes proporções. Constitui-se na principal causa de óbitos na população jovem. O Major Trauma Outcome Study (MTOS) é um estudo descritivo e retrospectivo da gravidade das lesões e evolução dos pacientes, considerado como o maior arquivo contemporâneo de informações descritivas de traumatizados. O objetivo do presente estudo é comparar o cálculo retrospectivo do New Injury Severity Score (NISS) com o Injury Severity Score (ISS) já calculado prospectivamente, utilizando o Trauma and Injury Severity Score (TRISS) e uma simples modificação deste índice, denominado de NTRISS (New Trauma and Injury Severity Score), e também comparar esta população submetida à laparotomia com os pacientes do MTOS. MÉTODO: Foram estudados 1.380 pacientes adultos traumatizados e submetidos à laparotomia na Disciplina de Cirurgia do Trauma da Unicamp, em Campinas, durante um período de oito anos. Os dados avaliados foram: demográficos, causa do trauma (fechado ou penetrante, ferimento por projétil de arma de fogo ou arma branca), estado fisiológico na admissão (RTS), diagnóstico anatômico de lesões (ATI, ISS e NISS), probabilidade de sobrevida utilizando o TRISS e o NTRISS, e a evolução do paciente (sobrevivência ou óbito). Foram utilizadas as estatísticas Z e W, inicialmente descritas por Flora, a fim de comparar a predição de óbitos ou sobreviventes com o estudo controle (MTOS). RESULTADOS: A maioria dos pacientes (88,3%) era do sexo masculino e jovem (média de idade de 30,4 anos). O ferimento por projétil de arma de fogo foi o mecanismo de trauma mais freqüente, com 641 casos (46,4%). Quatrocentos e trinta pacientes (31,2%) sofreram trauma fechado. As médias do ATI, ISS e NISS foram, respectivamente, de 12,3, 17,6 e 22,1. A taxa global de mortalidade foi de 16,8% e os pacientes com trauma contuso tiveram a maior mortalidade (29,3%). O NISS identificou melhor os sobreviventes e óbitos se comparado ao ISS, obtendo-se uma maior especificidade com o NTRISS. Foi observado um número significativamente menor de sobreviventes do que o esperado pelo estudo basal, com Z -16,24 com o TRISS e Z -9,40 se aplicado o NTRISS. Variações no valor da estatística W para cada paciente mostraram uma diferença no número de óbitos equivalente a 7,89 mais casos de óbito do que o esperado pelo MTOS, por 100 pacientes tratados, ao se empregar o TRISS, enquanto que estes valores foram reduzidos para 5,14 utilizando-se o NTRISS. CONCLUSÕES: Os métodos utilizados para cálculo da probabilidade de sobrevivência apresentaram limitações, particularmente nesta população com predomínio dos traumas penetrantes. O NISS, com o seu derivado NTRISS, foi o escore que obteve uma melhor predição de sobrevivência se comparado com o ISS. Os resultados obtidos com o TRISS e NTRISS foram estatisticamente piores do que os do MTOS, porém este processo de monitorização destes pacientes traumatizados tem sido importante para assegurar uma condição continuada de controle de qualidade.

A hemofilia é uma doença hemorrágica importante no Brasil, afetando cerca de um em cada dez mil indivíduos do sexo masculino. A autopercepção do portador a respeito da hemofilia e a sua interação com a comunidade são relevantes na abordagem clínica dessa doença. Nós investigamos vários aspectos sociais, psicológicos e comunitários da hemofilia em uma população brasileira (Campinas, São Paulo). Entrevistamos trinta portadores adultos da hemofilia, uma amostra-controle composta por 73 de seus irmãos normais do sexo masculino e 641 indivíduos da comunidade. A integração comunitária dos portadores da hemofilia mostrou-se afetada apenas nos aspectos sócio-econômicos, sem alteração no que diz respeito ao casamento, à procriação e à aquisição de melhores níveis educacionais. Observaram-se entre os portadores da hemofilia altos níveis de auto-rotulação, acompanhados de depressão, ansiedade e insegurança. A comunidade apresentou uma alta freqüência de completo desconhecimento a respeito da hemofilia (49%), demonstrando contra os hemofílicos os preconceitos normalmente observados contra os portadores de doenças contagiosas, como a AIDS. O trabalho sugere a estruturação de programa comunitário, visando à melhor adequação psicossocial dos portadores da hemofilia.

A hemofilia é uma doença hemorrágica importante no Brasil, afetando cerca de um em cada dez mil indivíduos do sexo masculino. A autopercepção do portador a respeito da hemofilia e a sua interação com a comunidade são relevantes na abordagem clínica dessa doença. Nós investigamos vários aspectos sociais, psicológicos e comunitários da hemofilia em uma população brasileira (Campinas, São Paulo). Entrevistamos trinta portadores adultos da hemofilia, uma amostra-controle composta por 73 de seus irmãos normais do sexo masculino e 641 indivíduos da comunidade. A integração comunitária dos portadores da hemofilia mostrou-se afetada apenas nos aspectos sócio-econômicos, sem alteração no que diz respeito ao casamento, à procriação e à aquisição de melhores níveis educacionais. Observaram-se entre os portadores da hemofilia altos níveis de auto-rotulação, acompanhados de depressão, ansiedade e insegurança. A comunidade apresentou uma alta freqüência de completo desconhecimento a respeito da hemofilia (49%), demonstrando contra os hemofílicos os preconceitos normalmente observados contra os portadores de doenças contagiosas, como a AIDS. O trabalho sugere a estruturação de programa comunitário, visando à melhor adequação psicossocial dos portadores da hemofilia.

O objetivo deste artigo foi averiguar o perfil do atendimento preventivo em deficiência mental na rede básica de saúde pública do Município de Maringá, Paraná, Brasil. A amostra foi composta por 90 médicos(as) das áreas de Ginecologia e Obstetrícia, Pediatria, Clínica Geral, Programa Saúde da Família e 66 enfermeiros(as). Foi aplicado questionário, por autopreenchimento, com respostas de múltipla escolha, entre agosto e dezembro de 2003. As variáveis qualitativas foram comparadas pelo teste do qui-quadrado, com nível de significância de 5%. São apresentados dados parciais relacionados à percepção e ao conhecimento de profissionais de saúde sobre deficiência mental: 75% não foram capazes de assinalar a alternativa correta sobre a prevalência; 25% não sabem qual a contribuição do genoma para a etiologia; 37% não sabem se existe prevenção para a deficiência mental; 28% não se sentem seguros para orientar sobre o efeito teratogênico do etanol; 35% referiram insegurança para orientar sobre amniocentese. Os dados demonstraram que os participantes têm baixa percepção da relevância da deficiência mental para a morbidade da população e necessitam de maiores informações sobre os aspectos genéticos e ambientais relacionados a tal condição.

Ao incluir as hemoglobinopatias no Programa Nacional de Triagem Neonatal (PNTN), a Portaria nº 822/01 do Ministério da Saúde deu um passo importante no reconhecimento da sua relevância em saúde pública no Brasil. No entanto, com exceção de alguns centros especializados, tal Portaria encontrou a maioria dos serviços públicos de saúde ainda despreparados para colocá-la em prática. Em uma fase inicial de implantação, é necessária, portanto, uma ampla divulgação das hemoglobinopatias entre os profissionais ligados à saúde pública, sobretudo entre aqueles que atuam na triagem neonatal. O presente artigo discute algumas das suas peculiaridades em relação aos demais distúrbios metabólicos incluídos no PNTN. Além disso, é proposta uma reflexão sobre alguns eventuais pontos de distorção que podem comprometer o êxito do programa.

O objetivo deste artigo foi averiguar o perfil do atendimento preventivo em deficiência mental na rede básica de saúde pública do Município de Maringá, Paraná, Brasil. A amostra foi composta por 90 médicos(as) das áreas de Ginecologia e Obstetrícia, Pediatria, Clínica Geral, Programa Saúde da Família e 66 enfermeiros(as). Foi aplicado questionário, por autopreenchimento, com respostas de múltipla escolha, entre agosto e dezembro de 2003. As variáveis qualitativas foram comparadas pelo teste do qui-quadrado, com nível de significância de 5%. São apresentados dados parciais relacionados à percepção e ao conhecimento de profissionais de saúde sobre deficiência mental: 75% não foram capazes de assinalar a alternativa correta sobre a prevalência; 25% não sabem qual a contribuição do genoma para a etiologia; 37% não sabem se existe prevenção para a deficiência mental; 28% não se sentem seguros para orientar sobre o efeito teratogênico do etanol; 35% referiram insegurança para orientar sobre amniocentese. Os dados demonstraram que os participantes têm baixa percepção da relevância da deficiência mental para a morbidade da população e necessitam de maiores informações sobre os aspectos genéticos e ambientais relacionados a tal condição.

CONTEXT: The integrity of basement membrane (BM) is damaged during the evolution of a benign or potentially malignant lesion into a malignant one, in which it may undergo several degrees of discontinuity as a necessary condition for the invasive process. Immunostaining for collagen IV, which is exclusively found in BM, has been used to evaluate its formation in neoplastic and benign lesions of several organs. OBJECTIVE: To investigate BM continuity pattern in squamous carcinoma "in situ" (CIS), microinvasive (MIC) and invasive (IC) squamous cell carcinoma of the uterine cervix, and to find out if BM expression could be useful in the diagnosis of early stromal invasion (MIC). DESIGN: Archival material between 1988 and 1993 was studied at the Pathological Anatomy Department - Unicamp. PROCEDURES: The selected cases, previously formalin fixed and paraffin embedded, were reviewed retrospectively by submitting them to immunohistochemical study via the avidin-biotin-peroxidase method using a monoclonal antibody anticollagen IV. RESULTS: In all, 17 cases of CIS, 16 of MIC and 21 of IC were evaluated. All IC cases showed evident BM discontinuity, either focal or diffuse. In the CIS group, a continuous BM pattern was predominant, being focally disrupted in only 2/17 cases (11.8%). The MIC group showed an intermediate pattern, but with a clear tendency to BM discontinuity in 10/16 cases (62.5%). Inflammatory infiltrate, a variable also studied, cannot be considered responsible for BM discontinuity, since there was no statistical correlation between them. CONCLUSION: We conclude that immunostaining for collagen IV may contribute to the diagnosis of stromal invasion by BM discontinuity.