Advanced endoscopic imaging methods for colon neoplasia

The main goal of lumenal endoscopic visualization of the colon is to detect mucosal pathologies, which when removed will result in cure or palliation of a disease process. Whereas traditionally endoscopic imaging was performed with fiber-optic technology, currently there are many new methods that improve our visual acuity when evaluating the colon mucosa. Most of these methods are collectively called 'advanced colonic imaging'. The 2 main aims of standard (white light) and advanced colonic imaging are to enhance the superficial mucosal detail (i.e. 'pit pattern') and allow a detailed view of the submucosal capillary pattern, thus potentially improving the detection characterization of pathological lesions. However, the current literature dealing with most methods used for advanced endoscopic imaging of the colon is fraught with many controversial findings which have resulted in opposing views regarding its utility. Whereas some investigators vehemently support the use of most of these methods in routine clinical practice, most experts and practicing endoscopists still refuse to accept that these methods aid in the clinical routine. For now, white light video-colonoscopy and high-definition white light video-colonoscopy will remain the standard endoscopic methods for investigating the colon mucosa until new methods convincingly and clearly prove their superiority over white light endoscopy.     

Calculating the insulin to carbohydrate ratio using the hyperinsulinaemic-euglycaemic clamp-a novel use for a proven technique

BACKGROUND: In patients with type 1 diabetes, three main variables need to be assessed to optimize meal-related insulin boluses: pre-meal blood glucose (BG), insulin to carbohydrate ratio (I : C), and basal insulin. We are presenting data for a novel use of the hyperinsulinaemic-euglycaemic clamp (HEC) in patients with type 1 diabetes that minimizes the impact of these variables and can be used to determine the I : C. METHODS: Ten subjects (six men and four women) using continuous subcutaneous insulin infusion (CSII) pumps were recruited for this study [24-65 years; BMI 27.1 +/- 4.9 kg/m(2); A1C 7.2 +/- 1.4% (mean +/- SD)]. The HEC used a primed continuous intravenous insulin infusion of 40 mU/m(2)/min and a variable infusion of 20% glucose to maintain BG at 90 mg/dL. After subjects were in steady state (SS) for 50 min, a standardized meal (40% of total calories/day - 30% carbohydrate, 30% protein, 40% fat) was consumed. Subjects gave the insulin bolus with their CSII pump. No changes were made in the glucose infusion rate. RESULTS: Mean BG at SS was 85.7 +/- 10.4 mg/dL. Peak BG was 115.0 +/- 12.7 mg/dL at 68.5 +/- 8.8 min after the meal. Mean I : C was 1 : 9.3 +/- 1.7 (range 1 : 7-1 : 12). Insulin sensitivity varied from 1.9 to 9.1 mg/kg/min. CONCLUSIONS: The HEC can be used to reduce confounding factors and to determine the I : C. As a first estimate of the I : C in patients with type 1 diabetes, it is recommended to start with a ratio of 1 : 9.3 and to measure post-prandial BG at 70 min.     

Effects of lowering dialysate calcium concentration on mineral metabolism and parathyroid hormone secretion: a multicentric study

This prospective study was conducted with the aim of examining the efficacy of lowering dialysate calcium (dCa) in order to: (i) stimulate bone turnover in hemodialysis patients with biochemical signs of adynamic bone disease (ABD) (hypercalcemia, normal alkaline phosphatase and intact parathyroid hormone (iPTH) <150 pg/mL); and (ii) diminish hypercalcemia in patients with secondary hyperparathyroidism (sHPT) (hypercalcemia, high alkaline phosphatase and iPTH > 400 pg/mL), thus permitting the use of calcium-containing phosphorus binders and vitamin D metabolites. Patients were divided into: an ABD-treated group (24 patients), a sHPT-treated group (18 patients), an ABD-control group (12 patients) and a sHPT-control group (11 patients). For the ABD- and sHPT-treated patients, hemodialysis was conducted with dCa 1.5 mmol/L for three months and then with dCa 1.25 mmol/L for an additional three months, while in the control groups hemodialysis was conducted with dCa 1.75 mmol/L during the entire study. Reduction of dCa in patients with ABD caused a slight but insignificant decrease of Ca, but a significant and permanent increase of bone-specific alkaline phosphatase and intact parathyroid hormone level serum levels. Reduction of dCa in patients with sHPT slightly but insignificantly decreased Ca and intact parathyroid hormone level values. Nevertheless, this enabled the calcium-based phosphate binder dose to be raised and vitamin D3 metabolites to be introduced. Logistic regression analysis indicated that milder bone disease (both ABD and sHPT) was associated with more the favorable effect of dCa reduction. Thus, low dCa stimulated parathyroid glands and increased bone turnover in ABD patients, and enabled better control of mineral metabolism in sHPT patients.     

The expression of Ki-67 and Bcl-2 in hodgkin’s lymphoma: Correlation with the international prognostic score and bulky disease

The prognosis of Hodgkin’s lymphoma has been improved over last 10 yr due to identification of prognostic parameters. These factors may predict the clinical outcome and therefore may have influence on the selection of appropriate treatment. In a cohort of 40 patients with Hodgkin’s lymphoma of nodular sclerosis subtype, treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen, we analyzed prognostic relevance of the expression of Ki-67 and Bcl-2 at diagnosis as well as other clinical parameters: International Prognostic Score, bulky disease, tissue eosinophilia, and high erythrocyte sedimentation rate. Significance was tested according to response rate and overall survival. Patients with a high proliferative fraction (Ki-67 > 50%) had worse overall survival compared with those with low proliferation, 56% vs 91%. There was a correlation between Ki-67 positivity and the achievement of complete remission. Cox’s multivariate model revealed that Ki-67 positivity at threshold of 50% was a significant independent prognostic factor. The Bcl-2 expression in less than 50% of tumor cells was detected in 65.5% of patients, and in a majority of cases it was associated with complete remission. Patients with high IPS had more progressive disease and shorter survival. Bulky disease, tissue eosinophilia, and high erythrocyte sedimentation rate had no significant influence on complete remission and survival. However, there was a marked divergence in survival curves after 4 yr follow-up for each of these parameters. Patients with high Ki-67, IPS > 3, bulky disease, tissue eosinophilia, and high sedimentation rate are at a higher risk of treatment failure and relapse and therefore might be eligible for other aggressive therapeutic approach.     

Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET

Women and men differ in serotonin associated psychiatric conditions, such as depression, anxiety and suicide. Despite this, very few studies focus on sex differences in the serotonin system. Of the biomarkers in the serotonin system, serotonin(1A) (5-HT(1A)) receptor is implicated in depression, and anxiety and serotonin transporter (5-HTT) is a target for selective serotonin reuptake inhibitors, psychotropic drugs used in the treatment of these disorders. The objective of the present study was to study sex related differences in the 5-HT(1A) receptor and 5-HTT binding potentials (BP(ND)s) in healthy humans, in vivo. Positron emission tomography and selective radioligands [(11)C]WAY100635 and [(11)C]MADAM were used to evaluate binding potentials for 5-HT(1A) receptors (14 women and 14 men) and 5-HTT (8 women and 10 men). The binding potentials were estimated both on the level of anatomical regions and voxel wise, derived by the simplified reference tissue model and wavelet/Logan plot parametric image techniques respectively. Compared to men, women had significantly higher 5-HT(1A) receptor and lower 5-HTT binding potentials in a wide array of cortical and subcortical brain regions. In women, there was a positive correlation between 5-HT(1A) receptor and 5-HTT binding potentials for the region of hippocampus. Sex differences in 5-HT(1A) receptor and 5-HTT BP(ND) may reflect biological distinctions in the serotonin system contributing to sex differences in the prevalence of psychiatric disorders such as depression and anxiety. The result of the present study may help in understanding sex differences in drug treatment responses to drugs affecting the serotonin system.     

Tuberculosis trends in Central Serbia in the period 1956-1996.

OBJECTIVE: To estimate tuberculosis incidence and mortality trends in Central Serbia (excluding Kosovo and Vojvodina provinces) in the period 1956-1996. DESIGN: The incidence and mortality data of tuberculosis in Central Serbia in the period 1956-1996 were analysed based on the annual reports of the Institute for Lung Diseases and Tuberculosis in Belgrade and the official data of the Republic Health Institute. RESULTS: During the period under observation, tuberculosis incidence decreased from 324.0 to 34.8/100 000 population, fitting the exponential model (y = 389.066e-(0.0689); F = 847.60; P = 0.000). Mortality rates decreased from 76.0 in 1956 to 0.9/100000 in 1982. Over the whole period (1956-1996) the decrease in mortality rates fitted the exponential model (y = 66.83e-(0.0922); F = 150.95; P = 0.000). The increase in mortality rates in the period 1982-1996 fitted cubic model (y = 7.647 - 2.674x + 0.359x(2)-0.013x(3); F = 12.17; P = 0.001). CONCLUSION: Decreasing trends in tuberculosis incidence are the result of good control programmes. Changes in mortality trends are related to migration from war zones and poor economic conditions which hinder the detection and treatment of tuberculosis.