Endothelial function and menopause: effects of raloxifene administration

Postmenopausal women have more severe endothelial dysfunction than premenopausal women. In the present study, we evaluated the possible beneficial effect of raloxifene administration, a selective estrogen receptor modulator, on endothelial regulation in postmenopausal women. In a double-blind, randomized vs. placebo trial, 60 healthy postmenopausal women were treated with raloxifene (60 mg/d) or placebo for 4 months to evaluate the effect of raloxifene treatment on endothelial function. Furthermore, in raloxifene-treated subjects (n = 30), the effect of raloxifene was also assessed during the intraarterial infusion of N(G)-monomethyl-L-arginine (4 micromol/min). Raloxifene administration vs. placebo was associated with a decrease in plasma low-density lipoprotein cholesterol (P < 0.01), triglyceride (P < 0.05), thiobarbituric acid-reactive substance (P < 0.01), vascular cell adhesion molecule-1 (P < 0.05), intercellular adhesion molecule-1 (P < 0.001), and E-selectin (P < 0.001) levels and with an increase in plasma Trolox equivalent antioxidant capacity (P < 0.001) levels. Indeed, raloxifene treatment was also associated with a significant improvement in endothelial-dependent vasodilatation assessed by brachial reactivity technique. Raloxifene administration had no impact on endothelial-independent vasodilatation. Furthermore, intraarterial infusion of N(G)-monomethyl-L-arginine inhibited the significant effect of raloxifene on endothelium-mediated brachial arterial diameter and flow. In conclusion, our results demonstrate that raloxifene administration is associated with a positive modulation of endothelial-dependent vasodilatation likely due to a reduction of risk factors for endothelial damage.     

Endometriosis

Endometriosis, a condition defined by the presence of ectopic endometrium, is a disorder of increasing incidence and a significant cause of gastroenterologic distress in young women. Although clinical manifestations vary considerably depending upon the anatomic extent of disease, characteristic abdominal complaints and typical physical findings continue to be associated with misdiagnosis and delayed recognition of gastrointestinal involvement. The authors of this paper review the medical literature concerning endometriosis of the digestive tract-emphasizing modes of presentation, risk factors, diagnostic testing, complications, and therapy. Greater familiarity with the disease and heightened awareness of its sequellae are needed and prerequisite to improved medical management.     

Lactitol in treatment of chronic hepatic encephalopathy

The efficacy and side effects of lactitol in the treatment of chronic hepatic encephalopathy was compared to that of other disaccharides in a meta-analysis of published randomized clinical trials (RCTs). The outcomes assessed were: (1) the rate of patients free from episodes of clinically detectable encephalopathy, and (2) the rate of patients free from one or more side effects in the different treatment groups. Four RCTs were eligible for analysis; in three lactitol was compared to lactulose, in one the alternative treatment was lactose in lactase-deficient patients. The methodological quality of these studies was high. Meta-analysis showed that lactitol was as effective as other disaccharides in the treatment of encephalopathy: pooled odds ratio was 0.83, 95% confidence interval was 0.38–1.82. Results were not sensitive to the use of alternative methods of counting and attributing events in these trials. Patients experienced fewer side effects during treatment with lactitol, but the pooled odds ratio was not statistically significant. In all studies lactitol was considered more palatable. Clinical effectiveness of lactitol, in long-term treatment of chronic encephalopathy, is similar to those of lactulose. It seems that lactitol has lower side effects than lactulose. Future RCTs with a double-blind design could be mainly aimed at evaluating the side-effect profile of the two disaccharides.This work was supported by grants from the Zyma S. A.     

Increased arterial stiffness in normoglycemic normotensive offspring of type 2 diabetic parents

Diabetes is associated with a reduction of arterial distensibility. Limited information exists regarding whether or how early this appears in the course of the disease. We studied 54 normoglycemic, normotensive, healthy offspring of 2 parents with type 2 diabetes mellitus and 55 age- and sex-matched healthy control subjects. Carotid diastolic diameter and systodiastolic change were measured by echo tracking (Wall Track System) and wall thickness by echocolor Doppler (Sonos 5500, Philips). Pulse pressure was measured by a semiautomatic device positioned on the brachial artery and arterial distensibility calculated by Reneman formula. Blood pressure, blood glucose, glycohemoglobin, and insulin sensitivity (homeostasis model assessment index) were normal or only slightly elevated and by and large similar in the 2 groups. Compared with control subjects, offspring of diabetic parents showed similar carotid diameters at diastole and a reduced increase in carotid diameter at systole (-16%), a reduced carotid artery distensibility (-30%), and an increased pulse pressure (+21.8%), all differences being statistically significant (P<0.05) and persisting in subgroups with elevated or normal body mass index values (<25 and >or=25 kg/m(2)). Carotid artery wall thickness was not different between the 2 groups. Thus, subjects with predisposition to diabetes show carotid artery stiffening even in the absence of blood pressure alterations, as well as substantial alterations of glucose metabolism, body mass index, and changes in carotid wall thickness. This suggests that, in diabetes, alterations in arterial mechanical properties represent an early phenomenon, which may occur in the absence of metabolic and blood pressure alterations.     

Revisions and Refinements of the Diagnosis of Schizophrenia in DSM‐5

The DSM‐5 changes to the diagnostic criteria for schizophrenia reflect modest incremental changes. The two most substantial changes, the elimination of subtypes and de‐emphasis of Schneiderian First‐Rank Symptoms, are a significant departure from long‐standing approaches to conceptualizing and defining schizophrenia, but are unlikely to have an appreciable impact on caseness or clinical management. Several minor modifications to the diagnosis are generally useful additions that will likely enhance diagnostic precision. The two most controversial changes that were considered, the addition of dimensional ratings and attenuated psychosis syndrome, were ultimately placed in the third section of DSM‐5 for further research and consideration. In sum, the changes demonstrate increased precision of diagnosis, with minimal changes in caseness.