Short-term treatment with ezetimibe, simvastatin or their combination does not alter circulating adiponectin, resistin or leptin levels in healthy men

Objective Statin therapy decreases cardiovascular morbidity and mortality, and ezetimibe, a novel cholesterol absorption inhibitor has both lipid‐lowering and anti‐atherosclerotic effects in animal models. As several adipokines, that is, adiponectin, high molecular weight (HMW) adiponectin, leptin and/or possibly resistin are involved in the pathogenesis of insulin resistance (IR), dyslipidaemia and atherosclerosis, we investigated whether ezetimibe and/or statin treatment may modulate serum concentrations of these four major adipokines. Research design and methods One‐centre, randomized, parallel three‐group study in 72 healthy men [mean age 32 ± 9 years, mean body mass index (BMI) 25·7 ± 3·2 kg/m²]. Patients Seventy‐two healthy men. Each group of 24 subjects received a 14‐day treatment with either ezetimibe (10 mg/day), simvastatin (40 mg/day) or their combination. Blood was drawn before and after the 14‐day treatment period. Measurements Lipid levels, IR indices, serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Results Neither ezetimibe nor simvastatin or their combination had any effect on serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Baseline leptin levels correlated positively, while adiponectin and HMW adiponectin negatively, with BMI. Leptin concentrations correlated negatively while adiponectin and HMW adiponectin positively with plasma high‐density lipoprotein‐cholesterol concentrations. Resistin concentrations were not associated with BMI, lipid levels or indicators of IR. Conclusions Treatment with ezetimibe, simvastatin or their combination does not alter circulating levels of adiponectin, leptin or resistin in adult healthy men.     

Reproducible lactulose hydrogen breath test as a measure of mouth-to-cecum transit time

Breath hydrogen monitoring after oral lactulose syrup is a conventional measure of mouth-to-cecum transit time (MCTT), but its reproducibility has been questioned. We compared the reproducibility of five measurements of MCTT after a conventional breakfast (380 kcal) taken with tea containing 20 g lactulose to five measurements of MCTT after 20 g lactulose in water in eight normal volunteers. Individual mean breakfast transit time was not significantly different from lactulose transit time in each of the seven subjects, but one had a breakfast transit time of 151±15 min and a lactulose transit time of 86±22 minutes (¯X ±sd, P<0.001). The coefficient of variation of breakfast transit time (11.6±5.3%, range: 6.9–24.2%) was less than that of lactulose transit time (30.7±7.8%, range: 22.1–50.0%, P<0.001). In a second set of experiments, the liquid phase marker ( ^99m Technetiumdiethylene triamine pentaacetic acid) emptied from the stomach more rapidly after the lactulose solution (T1/2 16.3±5.4) than after the breakfast (33.9±10.9 min, P<0.01) and MCTT was shorter after lactulose (77±32 vs 104±40 min, trespectively, P<0.05). There was no correlation between MCTT of lactulose and breakfast and between half-time gastric emptying and MCTT of either lactulose or breakfast. We conclude that the ingestion of inert lactulose induces an abnormally rapid MCTT and that breakfast MCTT is a much more reproducible investigation and should be employed in studies requiring serial measurements.     

Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression

Unipolar and bipolar depressive episodes have a similar clinical presentation that suggests common dysfunction of the brain’s reward system. Here, we evaluated the relationship of both dimensional depression severity and diagnostic category to reward system function in both bipolar and unipolar depression. In total, 89 adults were included, including 27 with bipolar depression, 25 with unipolar depression, and 37 healthy comparison subjects. Subjects completed both a monetary reward task and a resting-state acquisition during 3T BOLD fMRI. Across disorders, depression severity was significantly associated with reduced activation for wins compared with losses in bilateral ventral striatum, anterior cingulate cortex, posterior cingulate cortex, and right anterior insula. Resting-state connectivity within this reward network was also diminished in proportion to depression severity, most notably connectivity strength in the left ventral striatum. In addition, there were categorical differences between patient groups: resting-state connectivity at multiple reward network nodes was higher in bipolar than in unipolar depression. Reduced reward system task activation and resting-state connectivity therefore appear to be a brain phenotype that is dimensionally related to depression severity in both bipolar and unipolar depression. In contrast, categorical differences in reward system resting connectivity between unipolar and bipolar depression may reflect differential risk of mania. Reward system dysfunction thus represents a common brain mechanism with relevance that spans categories of psychiatric diagnosis.     

The diagnosis of Gestational Diabetes Mellitus and its impact on In Vitro Fertilization pregnancies. A pilot study

BackgroundIn Vitro Fertilization (IVF) is increasingly becoming a necessary mode of reproduction. This high risk group is prone to Gestational Diabetes Mellitus (GDM) which further exposes these pregnancies to an increased risk of adverse outcomes. In light of the limited data in the current literature, further investigation is needed regarding the time of GDM diagnosis in IVF pregnancies as well as the outcome of IVF pregnancies complicated by GDM.MethodsIn this three center pilot cross sectional study, the data of 101 singleton IVF pregnancies complicated by GDM were analyzed. Prompt GDM diagnosis in IVF pregnancies was accomplished by self-blood glucose monitoring (SMBG) from the first antenatal visit and confirmed by an OGTT. To evaluate pregnancy outcome, maternal and fetal complications in the 101 GDM IVF group was compared to 101 IVF as well as 101 spontaneous conceptions (SC). The three groups were matched by age. The effect of demographic and glycemic parameters on the outcome of GDM IVF pregnancies was investigated.ResultsGDM diagnosis was made before the 24th week in 37.6% of the GDM IVF group. The week of delivery was earlier for the GDM IVF group (37 ± 1.7) relative to the IVF (37.9 ± 0.9, p < 0.001) and the SC group (38.1 ± 0.8, p < 0.001). GDM IVF pregnancies exhibited greater preeclampsia rates and 84.8% underwent caesarian section. No significant difference regarding LGA and SGA birth weights was found. Complications of GDM IVF pregnancies were associated with the 1-h postprandial BG (r = 0.267, p = 0.007).ConclusionGDM screening in IVF pregnancies may be considered earlier than the 24th week. IVF pregnancies affected by GDM are prone to increased maternal and fetal complications which are associated with 1-h postprandial BG.     

Locoregional immunochemotherapy in primary and metastatic liver disease: meta-analysis and review of literature

BACKGROUND/AIMS: Primary and metastatic liver tumors are the most common malignancies that resist conventional chemotherapy and radiotherapy. Several immunotherapies have been attempted for cancer treatment on the basis of stimulating host immune response to tumors and recent development of combined targeting locoregional immunochemotherapy reported with promising results. However, the efficacy of this therapeutic modality is not yet widely established. METHODOLOGY: We reviewed the medical literature for publications dealing with the value of locoregional immunochemotherapy in patients with primary or metastatic liver tumors. RESULTS: We found that 5 and 7 studies have been controlled and inadequately controlled, respectively. Among 131 patients with primary liver cancer, 40 were treated with combined locoregional immunochemotherapy, and 20 with systemic immunochemotherapy, and 71 with systemic chemotherapy served as two control groups. Complete or partial response was observed in 32 out of 40 (80%) patients who received combined locoregional therapy, and in 10 out of 20 (50%) systemic immunochemotherapy controls (P = 0.03). Survival was three times higher in the patients who received combined locoregional therapy compared with systemic chemotherapy controls (18 vs. 5.6 months). Recurrence of tumor was higher in systemic immunochemotherapy controls (P = 0.003). Among 286 patients with metastatic liver disease, 180 patients were treated with combined locoregional immunochemotherapy and 106 patients with systemic immunochemotherapy. Response (complete or partial) was observed in 65 out of 98 (66.3%) patients who received combined therapy, and in 4 out of 26 (15.4%) controls (P < = 0.001). Survival was two-fold higher in the patients treated with combined therapy (21 vs. 10.5 months). Tumor recurrence was higher in the systemic immunochemotherapy controls (P < = 0.001). CONCLUSIONS: The observational studies indicate a plausible therapeutic rationale for the introduction of locoregional immunotherapy in patients with primary and metastatic liver disease.     

The associations between physical activity, inflammation, and coagulation markers, in people with metabolic syndrome: the ATTICA study.

OBJECTIVE: Metabolic syndrome is a condition that promotes atherosclerosis and increases the risk of cardiovascular mortality and morbidity. We evaluated whether leisure time physical activity is associated with the levels of inflammatory and coagulation markers, in people with metabolic syndrome. METHODS: From May 2001 to December 2002 we randomly enrolled 1514 men and 1528 women (>18 years old), without any clinical evidence of cardiovascular disease, stratified by age-gender (census 2001). The population of the study was divided into those who fulfilled the NCEP ATP III criteria for the metabolic syndrome (n=701 or 33% men and 13% women) and the rest of the participants (n=2341). We assessed the relationship between self-reported physical activity status and inflammatory, and coagulation markers [i.e., C-reactive protein (CRP), serum amyloid-A (SAA), interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, white blood cell (WBC) counts, and fibrinogen (FIB)], after taking into account the effect of several confounders. RESULTS: Of the non-metabolic syndrome group, 56% of men and 58% of women were classified as sedentary, while of the metabolic syndrome group 58% men and 72% women were sedentary. After controlling for various potential confounders we found that physically active individuals with the metabolic syndrome had 36% lower levels of CRP, 15% lower levels of WBC, 19% lower levels of SAA, 15% lower levels of TNF-alpha, 30% lower levels of IL-6 and 15% lower levels of FIB, compared to sedentary (all P<0.05). Similar results were observed in the non-metabolic syndrome group. CONCLUSIONS: The adoption of a physically active lifestyle is independently associated with lower levels of the investigated biomarkers in individuals with the metabolic syndrome. The latter may suggest a pathway for reducing cardiovascular events, even in high-risk people.     

A morphometric study of bone marrow angiogenesis in hairy cell leukaemia with clinicopathological correlations

Bone marrow angiogenesis has recently been implicated in the pathophysiology and course of various haematological malignancies. Little is known, however, about the significance of this phenomenon in hairy cell leukaemia (HCL). We evaluated various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemistry, in the bone marrow of 44 patients with typical HCL, before and after treatment with interferon-alpha (IFN-alpha). Overall, bone marrow from 103 HCL patients and 20 controls was examined. Microvessel density (MVD) and several size- and shape-related parameters were quantified in the region of most intense vascularization using image analysis. MVD, size-related parameters and the percentage of branching microvessels were higher in HCL than in controls. Likewise, perimeter counts were higher in partial/non-responders than in complete responders. Achievement of complete response was accompanied by smaller calibre microvessels. IFN-alpha induced a decrease in MVD and branching values in cases with diffuse marrow involvement. In univariate analysis, progression-free survival was adversely affected by MVD, branching and major axis length. Multivariate analysis indicated that MVD/branching independently affected progression-free survival and the likelihood of complete response. Our data suggest that the generation of bone marrow microvessels indicated an increased risk of progression and IFN-alpha treatment failure in HCL. Furthermore, the prognostic significance of angiogenesis requires the concomitant assessment of MVD and the complexity of the microvascular network.