Amsterdam criteria II and endometrial cancer index cases for an accurate selection of HNPCC families

Endometrial carcinoma (EC) is the second most common tumor in hereditary nonpolyposis colorectal cancer (HNPCC), with an incidence rate of 60% by the age of 70 in mutation carriers. The International Collaborative Group on HNPCC revised the Amsterdam criteria and proposed a new, wider definition including extracolonic cancers. The aim of our study was to evaluate the accuracy of a new definition called Amsterdam criteria II. We updated, reclassified and compared the pedigrees of 29 women, already reported as being affected by EC and having a colorectal cancer familial background, according to the two clinical diagnostic criteria for HNPCC (Amsterdam criteria I, ACI, and Amsterdam criteria II, ACII) after two periods of observation (1990-1995 and 1995-2000). According to ACII the frequency of HNPCC in the population under study increased from 0.9% to 3.7% in the period 1990-1995 and from 3.2% to 3.7% in the period 1995-2000. ACII allowed early detection of HNPCC families and thus made it possible to provide them with a suitable surveillance program and genetic testing.     

Nutritional and lifestyle determinants of DNA oxidative damage: a study in a Mediterranean population

In order to evaluate dietary and lifestyle determinants of oxidative DNA damage we used a modification of the 'comet assay' (single cell alkaline gel electrophoresis), with the fpg enzyme (formamidopyrimidine DNA glycosilase), to measure the basal level of DNA oxidation in peripheral lymphocytes donated by 71 healthy adults living in Florence, Italy. Detailed information about dietary and lifestyle habits was collected by two validated and standardized questionnaires; we also measured plasma concentrations of selected micro-nutrients (six carotenoids, retinol, alpha- and gamma-tocopherol). DNA damage, measured as percent DNA migrated in the comet tail (mean 4.67%, interquartile range 2.36-6.62%), was not associated with gender, age, weight, body mass index, physical activity or smoking history. A positive correlation with height and period of blood sampling emerged: DNA damage tended to be higher among taller subjects (P = 0.02) and in samples obtained in summer months (P = 0.02). Multivariate analyses showed a positive association with coffee (P = 0.01) and tomato consumption (P = 0.05). Instead, the consumption of cruciferous vegetables tended to be negatively associated with oxidative damage (P = 0.09). Furthermore, a positive non-significant association between the consumption of total vegetables and fresh fruit and DNA damage emerged (P = 0.08 and P = 0.10, respectively). The estimated intake of simple sugars showed a strong positive association with oxidative DNA damage (P = 0.01), while vitamin E showed a borderline positive association (P = 0.06). The plasma levels of several micro-nutrients did not appear to influence DNA damage. Our results, although based on a relatively small group of subjects, indicate that individual dietary and lifestyle habits only modestly affect the levels of lymphocyte DNA oxidation and suggest that specific dietary patterns, rich in fresh fruit and vegetables, are not clearly related to decreased oxidative damage in peripheral lymphocytes in a Mediterranean population.     

Interleukin-1 beta and interferon-gamma induce proliferation and apoptosis in cultured Schwann cells

This study reports that in Schwann cell tissue culture the administration of the two pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma), at different dosages, singly or in combination, can induce apoptosis and/or mitosis.Schwann cell apoptosis was maximal within 24 h of stimulation with 50 U/ml of IFN-gamma, while proliferation was at its peak within 24 h with 10 U/ml IL-1 beta, and both processes decreased progressively by 48 and 72 h. Moreover, the combination of the two cytokines did not show any synergistic effect. These data can be interpreted as a possible involvement of pro-inflammatory cytokines not only in myelin disruption but also in promoting remyelination.     

Arteriovenous brain malformations: is functional MR imaging reliable for studying language reorganization in patients? Initial observations

PURPOSE: To determine whether the blood flow abnormalities frequently associated with arteriovenous malformations (AVMs) can alter functional magnetic resonance (MR) imaging evaluation of language lateralization and whether reorganization of language function occurs in patients with brain AVMs. MATERIALS AND METHODS: Eleven patients with left-hemisphere brain AVMs and 10 age-matched control subjects were examined with 1.5-T blood oxygen level-dependent (BOLD) functional MR imaging. Verbal fluency, sentence repetition, and story listening tasks were performed. The functional MR imaging laterality index in the frontal and temporal lobes was defined as the (L - R)/(L + R) ratio, where L and R are the numbers of activated pixels in the left and right hemispheres, respectively. Statistical analyses were performed with Wilcoxon signed rank, Fisher exact, and Kruskal-Wallis tests. RESULTS: Control subjects had left-sided language dominance, although symmetric pixel counts were observed in the frontal lobes in two subjects and in the temporal lobes in one subject. Six patients had left-sided language dominance similar to that observed in control subjects. Five of these patients had AVMs outside frontal or temporal language areas, without flow abnormalities. Five patients had abnormally right-sided asymmetric indexes (below mean control subject value - 2 SDs), which suggested language reorganization (P <.05). Results of Wada examination and/or postembolization functional MR imaging performed in two of these patients showed that the abnormal laterality indexes were at least partly due to severe flow abnormalities that impaired detection of BOLD MR imaging signal intensity. CONCLUSION: These data suggest that flow abnormalities may interfere with language lateralization assessment with functional MR imaging.     

Insulin-like growth factor II and colorectal cancer risk in women.

Recently, a number of prospective studies showed evidence that the growth hormone/insulin-like growth factor I (IGF-I) axis may be important in the development of colorectal cancer. However, only a few studies have reported on the possible relationship of colorectal cancer risk with circulating levels of IGF-II, which are not growth hormone dependent and which do not vary with alterations in energy balance. In a case-control study of 102 cases and 200 matched controls nested within a cohort of 14,275 women in New York, we examined the relationship between colorectal cancer risk and prediagnostic serum levels of IGF-II. Conditional logistic regression analysis showed an odds ratio (OR) for colorectal cancer of 2.02 (95% confidence interval (CI): 0.83-4.93), comparing the upper to lower quintile of IGF-II. This association was slightly attenuated after excluding IGF-II measurements in serum samples taken within 1 year before case diagnosis (OR of 1.81; 95% CI: 0.71-4.64) and moderately attenuated after excluding IGF-II measurements in serum samples taken within 2 years before case diagnosis (OR of 1.47; 95% CI: 0.56-3.91). Adjustment for IGF-1, IGF binding protein (BP)-1, IGFBP-3, smoking, or body mass index did not substantially alter the association, whereas adjustment for IGFBP-2 moderately attenuated the relationship. Our results confirm those of three recent case-control studies, and collectively these results suggest a possible increase in colorectal cancer risk among subjects with comparatively elevated serum IGF-II. Mechanisms that might cause the increase in IGF-II levels are unknown but may include loss of parental imprinting of the IGF-II gene.     

C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC)

Objectives: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: A cross-sectional analysis was performed on anthropometric and hormonal data from 743 pre- and 1217 postmenopausal women. Body mass index (BMI) and waist circumference were used as indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding globulin (SHBG) were measured by immunoassays; free sex steroid concentrations were calculated.Results: BMI and waist circumference were positively correlated with estrogens in postmenopausal women and with C-peptide, free testosterone and inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I was positively associated with postmenopausal estrogens and androgen concentrations in all women.Conclusions: Sex-steroid concentrations appear to be regulated along several axes. Adiposity correlated directly with estrogens in postmenopausal women and with insulin, resulting in lower SHBG and increased levels of free sex steroids. Independent of adiposity and insulin, IGF-I was associated with decreased SHBG levels, and increased concentrations of androgens and postmenopausal estrogens.     

Advantages of short-time ureteric stenting for prevention of urological complications in kidney transplantation: an 18-year experience

We retrospectively studied the incidence of urological complications in a consecutive series of 590 patients (group B) who received a kidney transplant (KT) with a ureteral stent from January 1994 to December 2002. The ureteral stent was sewn to the bladder catheter during the surgical procedure and left in situ for a mean time of 10 days (range 8 to 12 days). The results were compared to a consecutive series of 414 patients who received a KT from March 1986 to December 1993 without a ureteral stent (group A). The two groups were comparable in terms of donor and recipient gender, ischemia time, delayed graft function, and chronic rejection incidence, but differed in mean donor age (44.1 vs 36.0 years), mean recipient age (45.4 vs 39.1 years), living/cadaveric donor rate (19.8% vs 11.9%), arterial lesions and bench reconstruction rate (11.1 vs 3.5%), as well as acute rejection episodes (11.7% vs 29.2%). Complications were seen in nine patients in group B (1.5%) and 17 patients in group A (4.1%) (P < .0001). Urinary leaks presented in two patients in group B (0.3%) and 11 patients in Group A (2.6%; P < .0001), while stenosis was present in six patients in group B (1.5%) and 7 in group A (1.2%) (P = NS). Urological complications such as urinary tract infection and macroscopic hematuria were similar in both groups. Time to presentation of a leak was within 2 weeks from KT in 10 patients (92.3%), while stenosis presented early in four patients (one in group B and four in group A). Of the stenoses, 69.3% presented late (beyond 12 weeks) in five patients in group B and three in Group A. In conclusion, our data suggest that routine use of double pigtail ureteral stent significantly decreased the incidence of leaks and early stenoses, but it did not modify late stenosis incidence. In the last decade, risk factors for urological complications have been increasing over time, namely, older donors and older recipients, living donation, length of dialysis, and the use of grafts with arterial lesions. Therefore we believe that a ureteral stent should be routinely considered to afford the advantage to protect the urinary anastomosis in the early postoperative period when the incidence of complications is highest, without the need of cystoscopy for its removal.