Juvenal Ricardo Navarro Góes

Comparative study of eosinophil chemotaxis, adhesion, and degranulation in vitro in ulcerative colitis and Crohn's disease

Background Eosinophils have been identified in tissues from patients with Crohns disease (CD) and ulcerative colitis (UC) but whether they contribute to IBD pathogenesis is unknown. This study aimed to investigate the functional activity and morphological aspects of peripheral‐blood eosinophils from IBD patients compared to those from healthy volunteers (HVs). Methods Eosinophils from HVs and CD and UC patients were purified using a Percoll gradient and then a immunomagnetic cell separator. Functional activity in inactivated and previously activated cells was investigated by measuring adhesion to fibronectin and chemotaxis to fMLP, and degranulation was measured by release of eosinophil peroxidase (EPO). Cell morphology was investigated using electron microscopy. Results Eosinophil adhesion to human fibronectin in both inactivated and PAF‐stimulated and PMA‐stimulated eosinophils was markedly higher in patients with CD than in either patients with UC or HVs. Similarly, the chemotactic response was markedly higher in eosinophils isolated from CD patients than in those isolated from UC patients or HVs. Baseline EPO release was higher in eosinophils isolated from UC patients than in those isolated from HVs or CD patients. Stimulation with fMLP or PMA did not further increase EPO release in cells from UC or CD patients. Comparable expression of MAC‐1 and VLA‐4 adhesion molecules was observed on the surfaces of eosinophils from all groups, and an greater number of granules was noted in the eosinophils from UC patients than in those from CD patients. Conclusions Our results indicate that peripheral‐blood eosinophils are potentially primed and activated in IBD patients. Whether the differences in the morphology and functional responses of eosinophil from UC and CD patients reflect differences in disease phenotype remains to be elucidated. (Inflamm Bowel Dis 2007)

Differential expression of pro-inflammatory cytokines and a pro-apoptotic protein in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis

BackgroundPouchitis after total rectocolectomy is among the most common complications of patients with ulcerative colitis (UC). However, its frequency is quite rare in patients with familial adenomatous polyposis (FAP). We evaluated the inflammatory and pro-apoptotic activity in endoscopically normal mucosa of the ileal pouch in patients with UC and FAP.MethodsTwenty patients (10 with UC and 10 with FAP) with “J” pouch after total proctocolectomy were studied as were 10 normal controls. Biopsies were obtained from the mucosa of the pouch of UC and FAP patients and from the normal ileum of controls. The expression levels of TNF-α, IL-1β, IL-6, IL-8 and phospho-BAD were determined by immunoblotting. Activated NFκB was evaluated by immuno-precipitation and immunoblotting for IkappaB kinase beta.ResultsPatients with UC had higher levels of IL-1β, IL-6, IL-8 and TNF-α than patients with FAP. The level of TNF-α was higher in patients with UC than in patients with FAP; both patient groups had TNF-α levels higher than controls. Activation of NFκB was similar in all three groups. The expression of phospho-BAD was significantly lower in patients with FAP than in patients with UC.ConclusionsAs compared with patients with FAP, patients with UC presented increased levels of some pro-inflammatory cytokines, even in the absence of clinical or endoscopic signs of pouchitis. Patients with FAP presented lower levels of pro-inflammatory proteins and of phospho-BAD. These findings may explain the higher rates of progression to pouchitis in UC patients, which could correlate with mucosal atrophy that occurs in inflamed tissue.

Possible influence of glutathione S-transferase GSTT1 null genotype on age of onset of sporadic colorectal adenocarcinoma

AbstractINTRODUCTION: Glutathione S-transferase enzymes mediate exposure to cytotoxic and genotoxic agents and may be involved in cancer susceptibility. Both glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The association of glutathione S-transferase null genotype and risk of developing colorectal cancer is not yet fully clarified. METHODS: We tested whether the null genotypes for GSTM1 and GSTT1 genes altered the risk for sporadic colorectal adenocarcinoma in Brazilian patients. Genomic DNA from 102 sporadic colorectal adenocarcinoma patients and 300 controls was analyzed by polymerase chain reaction. RESULTS: Frequencies of GSTM1, GSTT1, and null combined genotypes were similar in patients and controls (49.9 vs. 44.6 percent, 16.6 vs. 17.3 percent, and 8.8 vs. 8 percent, respectively). We found a 1.03-fold (95 percent confidence interval, 0.96–1.10) and 1.08-fold (95 percent confidence interval, 0.99–1.18) increased risk associated with GSTM1 and GSTT1 null genotypes, respectively (P = 0.45 and P = 0.08) and a 1.18-fold (95 percent confidence interval, 0.47–2.90) increased risk associated with the combined null genotype (P = 0.74). The GSTT1 null genotype was more common in patients who were diagnosed before the age of 60 years than in those who were diagnosed at an older age (28.8 vs. 4 percent, respectively; P = 0.0008). CONCLUSIONS: The results suggest that inherited absence of this carcinogen detoxification pathway may not be associated with sporadic colorectal adenocarcinoma in the present cases. However, a higher frequency of GSTT1 null genotype in patients diagnosed before the age of 60 years suggests that this genotype could influence the age of disease onset in Brazil.

Estudos biomecânicos da ação de aderências sobre anastomose cólica: trabalho experimental em ratos

PURPOSE: To evaluate the influence of abdominal adhesions in the distal colonic anastomoses in rats using biomechanical tests. METHODS: Ninety Wistar-CEMIB (UNICAMP) rats were distributed in 3 groups. In group 1 the analysis was performed by bursting strength test, in group 2 by breaking strength test and in group 3 by final resultant tension test. In each group, 10 animals were characterized by the presence of adhesions in the anastomoses during the biomechanical test performance, 10 animals had the anastomoses adhesions removed before the test and 10 animals were free of adhesions in the anastomoses during the test (protection by P.V.C. sheet in the anastomoses area). RESULTS: Evaluations were made on the 5th post-operatory day and independent of the test performed, the results were similar. The mechanical resistence in the subgroups characterized by the presence of adhesions in anastomoses were higher than subgroups with anastomoses adhesions removed. The subgroups free of adhesions in the anastomoses (P.V.C. protection) demonstrated the lowest mechanical resistance in anastomoses breakdown (Group 1-p=0,0001, Group 2-p=0,0003 and Group 3-p=0,0001). CONCLUSION: Analysis of the results allowed to conclude that abdominal adhesions presented benefic influence in the distal colonic wound healing process in rats thus increasing mechanical resistance of the anastomoses.

Incontinência fecal em mulheres na pós-menopausa: prevalência, intensidade e fatores associados

BACKGROUND Fecal incontinence occurs more frequently in the female population and it becomes more prevalent with increasing age. There are few studies that have assessed the prevalence and severity of postmenopausal women. AIMS To investigate fecal incontinence. PATIENTS AND METHODS A cross-sectional study was performed on 100 postmenopausal women over the age of 45. Sociodemographic and clinical characteristics were evaluated, and a descriptive analysis of these characteristics was carried out. The prevalence of fecal incontinence was estimated. St. Marks incontinence score was applied to study the severity of symptoms associated with fecal incontinence. The score was then categorized according to the tertile and symptom severity was classified as mild, moderate or severe incontinence. Bivariate and multivariate analyses were used to study the association between fecal incontinence and its likely determinants, employing the prevalence ratio. Confidence interval was set at 95%. RESULTS The mean age of the patients was 58.9 +/- 5.9 years (range, 46-76 years). The prevalence rate was 15% for fecal incontinence. Of incontinent patients, 60% had mild incontinence. After multivariate analysis, factors associated with fecal incontinence was history of forceps delivery (prevalence ratio: 7.80; 95% confidence interval:2.38-25.55). CONCLUSIONS The prevalence of fecal incontinence was high in postmenopausal women. Data suggest that most women presented mild fecal incontinence. The history of forceps delivery was associated with fecal incontinence.

Prevalência e fatores associados à constipação intestinal em mulheres na pós-menopausa

BACKGROUND Constipation occurs more frequently in the female population and it becomes more prevalent with increasing age. There are few studies that have assessed the prevalence of constipation in postmenopausal women. AIM To investigate the prevalence and factors associated with constipation in postmenopausal women. PATIENTS AND METHODS A cross-sectional study of postmenopausal women aged over 45 years was conducted. It included 100 women who sought medical attention at the Menopause Outpatient Facility at the State University of Campinas (UNICAMP), Campinas, SP, Brazil, between March, 2003 and January, 2004. The prevalence of constipation was assessed according to the Rome II criteria. Sociodemographic and clinical features of these patients were studied. Physical examinations were performed to evaluate genital dystopias and anal sphincter tone. Statistical analysis was performed by using the mean, standard deviation, median, relative and absolute frequencies and by using the prevalence ratio with a 95% confidence interval and multiple logistic regression. RESULTS The mean age of the participants was 58.9 +/- 5.9 years and the mean age was 47.5 +/- 5.4 years at menopause. The prevalence of constipation was 37%, the most common symptom being excessive straining when defecating (91.9%), followed by a feeling of incomplete evacuation (83.8%), hard or lumpy stools (81.1%), less than three bowel movements per week (62.2%), sensation of anorectal obstruction during defecation (62.2%) and digital maneuvers to facilitate defecation (45.9%). Bivariate analysis showed that anal sphincter tone and the history of perianal surgery were factors associated with constipation. After applying multiple regression analysis, the history of perianal surgery was significantly associated with constipation (prevalence ratio: 2.68; 95% confidence interval: 1.18-6.11). CONCLUSIONS The prevalence of constipation in postmenopausal women was high. The history of perianal surgery was significantly associated with constipation, even when the influence of other variables were taken into consideration.

Mucinous adenocarcinoma derived from chronic perianal fistulas: report of a case and review of the literature

Chronic perianal fistulas are a common clinical condition. However, their evolution into adenocarcinoma is rare. We report the case of a 68-year-old man with perineal and perianal chronic fistulas, who developed a perineal mass that extended proximally as a pararectal tumor. Diagnosis was confirmed by magnetic resonance imaging (MRI). Histopathological sections indicated extramucosal mucinous adenocarcinoma. No intestinal lesion was seen at endoscopic examination. The patient underwent abdominal perineal excision of the rectum without neoadjuvant or adjuvant therapy, and had a good postoperative outcome.

Quantificação da função esfincteriana pela medida da capacidade de sustentação da pressão de contração voluntaria do canal anal

Verificou-se que pacientes incontinentes submetidos a manometria anorretal podem apresentar pressao media de repouso e pressao maxima de contracao voluntaria dentro da faixa de normalidade. A partir da constatacao de que as medidas de pressao media de repouso e pressao maxima de contracao voluntaria (PMCV) esfincteriana nao refletem a real situacao clinica do paciente, levantou-se a hipotese de a capacidade de sustentacao da pressao de contracao (CS) seria uma medida mais correta para a avaliacao da continencia fecal, no que diz respeito a funcao de contracao esfincteriana. Foram incluidos no estudo 72 pacientes portadores de incontinencia fecal em graus variados, desde escapes ocasionais de fezes e de gases ate incontinencia franca a fezes solidas, e 15 individuos normais, escolhidos, aleatoriamente, entre os pacientes encaminhados devido a outras queixas ou situacoes, como: proctalgia, prurido anal, pre-operatorio de reconstrucao de trânsito intestinal e pre-operatorio de cirurgia de coluna lombossacra. Todos os individuos normais nao apresentavam queixas de incontinencia fecal de qualquer grau. Os pacientes incontinentes e os individuos normais foram submetidos a manometria anorretal onde foram analisados os seguintes parâmetros: pressao media de repouso (PMR), pressao maxima de contracao voluntaria (PMCV), capacidade de sustentacao da pressao de contracao voluntaria (CS) . Entre os pacientes incontinentes, 39(54%) apresentaram niveis normais de PMCV e 33(46%) PMCV abaixo do normal; e todos os individuos normais apresentaram PMCV em nivel normal. Em relacao a CS, verificou-se que 56(78%) dos pacientes incontinentes apresentaram capacidade inadequada. A medida da PMCV apresentou excelente especificidade (100%), porem, baixa sensibilidade (46%) para incontinencia fecal. Comparativamente, a medida da CS apresentou alta especificidade (93%) e alta sensibilidade (78%) para incontinencia fecal. Alem disso, a medida da PMCV nao indicou falso positivo (PF+ = 0), mas, em compensacao, apresentou 72% de falso negativo. A probabilidade deste fato ocorrer com a medida da CS foi, praticamente, 20% menor, valor estatisticamente significante. Concluindo, a medida da CS e um bom indicativo da funcao esfincteriana do canal anal em relacao a continencia fecal Abstract

Constipação intestinal em mulheres na pós-menopausa

OBJECTIVES To investigate the prevalence and factors associated with constipation in postmenopausal women and evaluate the level of agreement between different diagnostic criteria. METHODS A cross-sectional study was conducted with 100 postmenopausal women more than 45 old. The Rome II criteria, stool frequency per week and patient self-evaluation were the diagnostic criteria applied. Social demographic and clinical characteristics with their descriptive analysis were assessed. Subsequently, kappa (ê) statistics was used to assess the level of agreement between diagnostic criteria. The association between constipation and its possible determinants was studied by bivariate and multivariate analyses, using the prevalence ratio (PR). The confidence interval was set at 95% (95% CI). RESULTS The mean age of participants was 58.9+/-5.9 years (range, 46-76 years). The prevalence of constipation was 47%, 37% and 26%, according to patient self-evaluation, the Rome II criteria and < 3 bowel movements per week, respectively. The best agreement found was between patient self-evaluation and the Rome II criteria (k: 0.63; 95% CI: 0.48-0.78). After multivariate analysis, the history of perianal surgery (PR: 2.69; 95% CI: 1.03-7.01), according to the Rome II criteria; the presence of hemorrhoids, according to stool frequency (PR: 2.53; 95% CI: 1.16-5.51) and patient self-evaluation (PR: 1.78; 95% CI: 1.01-3.15) were associated with constipation. CONCLUSIONS Prevalence of constipation in postmenopausal women was high. Agreement between diagnostic criteria ranged from moderate to good. History of perianal surgery and presence of hemorrhoids were associated with constipation.

Family history of cancer in Brazil: is it being used?

In developing countries, low budgets make the issue of integrating genetics into clinical practice a challenge, a situation in which the use of family history (FH) becomes important for patient care, as it is a low cost strategy and a risk assessment tool. The purpose of this study was to review medical records of patients with colorectal cancer (CRC) seen in a public University Hospital and evaluate how often FH of cancer is registered. Initially we searched a database for patients who were seen in our hospital between 2002 and 2004 with the diagnosis of CRC. We found 415 patients, 104 of whom were excluded. A total of 311 charts were reviewed and classified into 3 groups. Group A: no FH documented; group B: FH was documented, but FH of cancer was not collected; and group C: FH of cancer was documented. We also investigated what type of information was recorded, in order to verify if important elements were assessed. Ninety-eight charts (31.5%) were classified in group A, 20 (6.5%) in group B, and 193 (62%) in group C. In addition, we observed that important information regarding affected relatives was not collected in most of the charts. In conclusion, we found that although FH of cancer was recorded in 62% of charts of patients with CRC, information that could be relevant for risk assessment and management of at-risk families was missing. Our findings expose an important problem in health education that could reflect negatively in the quality of medical assistance to individuals at risk for familial cancer.