Clinicopathologic study of vascular endothelial growth factor, thrombospondin-1, and microvessel density assessed by CD34 in patients with stage III ovarian carcinoma.

The aim of the study was to investigate angiogenesis in patients with advanced-stage ovarian carcinoma. We used paraffin-embedded tumor tissues from 33 patients diagnosed with FIGO III ovarian cancer who had optimal surgery and received platinum-based chemotherapy. The tissue expression of CD34, vascular endothelial growth factor (VEGF), and thrombospondin-1 (TSP-1) was assessed immunohistochemically. CD34 stained hot spot areas were used to evaluate tumor microvessel density (MVD). VEGF and TSP-1 were assessed by semiquantitative methods. The studied molecules were investigated for relationship with standard clinicopathologic parameters. MVD count was high: median value of 39, range 12-143 microvessels/mm2. VEGF was present in all cases and stained strong in 91%. Stroma staining for TSP-1 was weak in 79% of the cases, strong in 6%, and absent in five (15%). We did not find correlations between the three studied markers and histologic type or tumor grade. MVD score did not relate to VEGF or TSP-1. We only observed a trend toward a longer survival in patients with tumors expressing high TSP-1 (60 vs. 36 months, P= 0.1). Proangiogenetic factor VEGF is highly expressed in advanced-stage ovarian carcinomas. The findings of this study may offer support for considering VEGF-targeted therapeutics in ovarian cancer treatment research.

Plasma homocysteine levels in patients with type 2 diabetes in a Mediterranean population: relation with nutritional and other factors.

BACKGROUND AND AIM: Hyperhomocysteinemia is a major and independent risk factor for atherothrombotic vascular disease. It may be promoted by genetic factors, nutritional deficiencies of the vitamin cofactors required for homocysteine metabolism, and other modifiable factors. This cross-sectional study investigated the effect of dietary habits and lifestyle on plasma total homocysteine (tHcy) levels in patients with type 2 diabetes in a Mediterranean population. METHODS AND RESULTS: A total of 126 diabetic and 76 healthy subjects were interviewed using a food-frequency questionnaire. Information consisted of dietary and smoking habits, coffee and alcohol consumption and physical activity recording, during the month prior to enrollment. Measurements included blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), plasma tHcy, folate, vitamin B12, lipids, HbA(1c), creatinine, uric acid, and glomerular filtration rate (GFR). Plasma tHcy levels were not different between diabetic and control subjects (11.49+/-3.68 vs 12.67+/-3.79 micromol/l respectively, P = 0.40). Diabetic subjects had significantly higher plasma folate levels and consumed more fish, fruit and vegetables, in comparison with controls. Controls consumed more red meat, coffee, and alcohol. Multivariate analysis in diabetic subjects, after controlling for age, sex, systolic blood pressure, duration of diabetes, GFR, plasma uric acid levels, and the amount of the weekly consumption of fruit and vegetables, demonstrated that age, GFR and the weekly amount of fruit and vegetable consumption were independently associated with plasma tHcy concentrations [regression coefficient (B) = 0.11, SE (B) = 0.03, P = 0.001, B = -0.07, SE (B) = 0.01, P < 0.0001, and B = -0.05, SE (B) = 0.02, P = 0.04, respectively]. The weekly amount of coffee, alcohol and red meat consumption, and physical activity level were not related with plasma tHcy levels in either study group. CONCLUSIONS: 1) Plasma tHcy levels were not different in the diabetic group as compared to the control group. 2) In patients with type 2 diabetes age, GFR and the consumption of fruit and vegetables were strong and independent determinants of plasma tHcy levels.

Autonomic neuropathy and gastrointestinal motility disorders in children and adolescents with type 1 diabetes mellitus.

INTRODUCTION: There is little information on the gastrointestinal motility abnormalities and autonomic neuropathy of children with gastrointestinal symptoms and type 1 diabetes mellitus (T1DM). METHODS: The authors studied 33 consecutive patients (mean age, 15.3 years; 13 males) with T1DM (median duration, 7.7 years) attending the outpatient clinic because of chronic dyspepsia (CD; n = 14), or chronic constipation (CC; n = 19), and 48 consecutive non-T1DM patients (mean age, 13.7 years; 18 males), who presented with similar symptoms (18 with CD; 30 with CC). Fasting serum motilin concentrations and cardiovascular autonomic function tests (CAFT) were assessed and compared with those of age- and gender-matched healthy control subjects. Gastric emptying half time (GE t1/2) of a solid meal and mouth-to-anus transit time (MATT) were measured in patients with CD and CC, respectively. RESULTS: CAFT was comparable between patients with T1DM and healthy control subjects. GE t1/2 and MATT were not different between T1DM patients and non-T1DM patients with CD and CC, respectively. However, a marginally significant positive correlation was found in the patients with T1DM between GE t1/2 and blood glucose concentrations (R = 0.54; P = 0.08). In addition, serum motilin concentrations were significantly lower in patients with T1DM compared with healthy control subjects (P < 0.0005), and in patients with T1DM and higher serum glucose concentrations compared with those with lower serum glucose concentrations (P = 0.03). CONCLUSION: Autonomic neuropathy is not an etiological factor of gastrointestinal symptoms in children and adolescents with diabetes. Mild or moderate hyperglycemia does not affect gastrointestinal motility.

Glycoprotein CD44 expression in normal, hyperplasic and neoplastic endometrium. An immunohistochemical study including correlations with p53, steroid receptor status and proliferative indices (PCNA, MIB1).

PURPOSE OF INVESTIGATION: We have studied by immunohistochemistry the presence and localization of CD44, estrogen and progesterone receptors, p53 and proliferative associated indices (MIB1, PCNA) in archival endometrial tissue, in order to determine their diagnostic and prognostic value as well as the possible correlations between them. METHODS: We examined 186 samples of endometrial tissue (100 endometrial carcinomas of endometrioid type, 40 cases of hyperplasia and 46 of normal endometrium). Patient records were examined for FIGO stage, grade, and depth of myometrial invasion, histology, and lympho-vascular space invasion. RESULTS: Strong membranous immunostaining (> 10% of neoplastic cells) was observed in 45% of the carcinomas. A statistically significant correlation was found in the expression of protein in stromal cells, when compared with epithelial cells (p < 0.0001). Immunohistochemical expression of CD44 was significantly lower in cancer cases than in normal endometrium, mainly in the secretory phase (p < 0.0001). CD44 positive cases by immunohistochemistry failed to show any statistical correlation with tumor grade or with vessel invasion. The expression of the protein was lower in FIGO Stage II compared with Stage I (p = 0.03). A positive relation of CD44 expression with progesterone receptor status (p = 0.02) was detected. CD44 expression was also positively associated with the proliferation associated with the proliferative index MIB1 (p = 0.001). CONCLUSION: CD44 is closely related to the secretory phase of the normal menstrual cycle and its expression is decreased in hyperplasia (simple or complex with or without atypia) and in cancer cases. These observations suggest that decreased CD44 expression might be functionally involved in the multiple mechanisms of the development and progression of endometrial lesions.

Differential effects of high-fat and high-carbohydrate isoenergetic meals on cardiac autonomic nervous system activity in lean and obese women.

Food ingestion can influence autonomic nervous system activity. This study compares the effects of 2 different isoenergetic meals on sympathetic nervous system (SNS) activity, assessed by heart rate variability (HRV) and plasma norepinephrine (NE) levels, in lean and obese women. Fifteen lean and 15 obese healthy women were examined on 2 occasions: after a carbohydrate (CHO)-rich and after a fat-rich test meal. Measurements of blood pressure, heart rate, resting energy expenditure, plasma glucose, lipids, insulin, leptin, and NE, as well as spectral analysis of the HRV, were performed at baseline and every 1 hour for 3 hours after meals. At baseline, obese women had higher SNS activity than lean controls (higher values of low-to-high frequency ratio [LF/HF], 1.52 +/- 0.31 v 0.78 +/- 0.13, P=.04; and plasma NE levels, 405.6 +/- 197.9 v 240.5 +/- 95.8 pg/mL, P<.0001). After the CHO-rich meal a greater increase in LF/HF and in plasma NE levels was observed in lean, compared to obese women (1.21 +/- 0.6 v 0.32 +/- 0.06, P=.04; and 102.9 +/- 35.4 v 38.7 +/- 12.3 pg/mL, P=.01, respectively), while no differences were observed after the fat-rich meal. Meal-induced thermogenesis was higher after the CHO-rich as compared to the fat-rich meal and was comparable between lean and obese women. Changes in HRV were not associated with the thermogenic response to the test meals. In conclusion, consumption of a CHO-rich meal causes greater cardiac SNS activation in lean than in obese women, while fat ingestion does not result in any appreciable change in either group. SNS activation does not appear to influence the thermic effect of the food in either lean or obese women.

Lack of effect of acute repaglinide administration on postprandial lipaemia in patients with type 2 diabetes mellitus.

The effect of acute repaglinide administration (2 mg) on postprandial glycaemia and lipaemia has been examined in 20 subjects with type 2 diabetes mellitus. Each subject received in the morning, after a 12 to 14 h fast, a standard mixed meal (total energy 783 kcal), preceded by one tablet of 2 mg repaglinide or placebo. Chylomicrons and chylomicron-deficient plasma were prepared by ultracentrifugation. Triglyceride levels in CM fraction (CM-triglycerides) in total plasma as well as in CM-deficient plasma (non-CM-triglycerides) were determined. A significant reduction in postprandial glycaemia was observed after repaglinide administration compared to placebo ( p < 0.001). Plasma concentrations of total triglycerides, CM-triglycerides, non-CM-triglycerides, free fatty acids and the other plasma lipids measured, were not significantly different between the two phases of the study. It is concluded that, in contrast to sulphonylureas, acute repaglinide administration does not improve postprandial lipaemia in patients with type 2 diabetes.

Immunohistochemical expression of heat shock protein 27, in normal hyperplastic and neoplastic endometrium: correlation with estrogen and progesterone receptor status, p53, pRb and proliferation associated indices (PCNA, MIB1).

Heat shock protein 27 (HSP27) is a relatively small protein produced in response to pathophysiological stress. In the current prospective study the presence and localization of HSP27 was associated with other potential prognostic factors such as: estrogen and progesterone receptors, p53 and proliferative associated indices (MIB1, PCNA). One hundred and twenty-two samples of endometrial tissues (65 endometrial carcinomas, 28 adenomatous hyperplasias, 31 normal endometrium) were studied. Patient records were examined for FIGO stage, grade, and depth of myometrial invasion, histology and lympho-vascular space invasion. HSPp27 expression was lower in the group of carcinomas when compared with the cases of adenomatous hyperplasias (p < 0.0001), normal proliferative (p < 0.0001) and secretory endometrium (p = 0.02). HSP27 expression was higher in carcinomas from premenopausal women in comparison with women in menopausal status and postmenopausal status. Multivariate tests showed no statistical significance of HSP27 expression according to tumor grade and stage. A positive relationship between the expression of HSP27 expression and estrogen receptors (p = 0.0018) as well as with progesterone receptor (p = 0.0012) was found with linear regression analysis of variance. Our data showed that the lower HSP27 expression in endometrial carcinomas in comparison with hyperplastic and normal endometrium may indicate a decreased endogenous protection mechanism against the various stressful stimuli. This expression could be under hormonal control and does not seem to be correlated with other conventional or possible prognostic parameters.

99mTc Tetrofosmin imaging in breast tumours.

Eighty-five women, 18 to 80 years of age, with palpable breast lumps were studied 1-4 days before surgery in order to evaluate 99mTc Tetrofosmin imaging for the detection of malignant breast tumours. Intravenous injection of 99mTc Tetrofosmin was followed by 3 min planar images at 5-60 min postinjection. In the latter 57 patients, planar imaging was preceded by a dynamic study of 20x5 sec images. The myocardium was always included in the field of the left breast. Count rates in suspicious areas were compared with normal tissue areas in the same and the opposite breast and with myocardial counts. Data analysis showed that 77 of the 85 scan results were in agreement with the histological findings; six scans were false negative and two false positive for malignancy. The sensitivity of the method was 90.32% and the specificity 91.30%, with a positive predictive value of 96.55%. We conclude that breast scanning with 99mTc Tetrofosmin may play an important role in the detection of breast malignancies.