Splanchnic and systemic haemodynamic response to volume changes in patients with cirrhosis and portal hypertension

We investigated the haemodynamic response to volume depletion and subsequent repletion in patients with cirrhosis and portal hypertension. Twelve patients with compensated cirrhosis and portal hypertension were included in the study. The haemodynamic changes occurring after removal of approx. 15% of the blood volume, and subsequently after isovolume repletion with colloid, were assessed. Baseline haemodynamic measurements showed increased cardiac output and a systemic vascular resistance at the lower limit of normal. The hepatic venous pressure gradient (HVPG) was increased, at 18 mmHg. After depletion, arterial pressure, cardiac output and all right-heart-sided pressures decreased, and systemic vascular resistance increased. HVPG decreased to 16.0 mmHg. All the above changes were statistically significant. After blood volume restitution, the haemodynamic values returned to baseline. In particular, an increase in HVPG was shown in four out of the twelve patients (two with ascites and two without), which was small in three of them. However, HVPG remained the same as or lower than the baseline in the other eight patients. Patients with cirrhosis and portal hypertension exhibit an abnormal haemodynamic response to blood volume depletion. After volume repletion, no increase in the portal pressure was noted in this group of patients as a whole, although four out of the twelve patients did show an increase, possibly due to extensive collateral circulation.     

Endothelial adhesion molecules ICAM-1, VCAM-1 and E-selectin in patients with acute coronary syndrome

INTRODUCTION AND OBJECTIVES: The acute inflammatory response is an important phenomenon in the pathogenesis of myocardial damage during acute coronary syndrome. Endothelial dysfunction has been found in unstable angina and acute myocardial infarction, although the results are controversial. The purpose of this study was to determine the levels of the soluble endothelial adhesion molecules ICAM-1, VCAM-1 and E-selectin, in patients with unstable angina and acute myocardial infarction, compare the results in both groups, and analyze their relation with the degree of myocardial injury. METHODS: Serum concentrations of ICAM-1, VCAM-1, and E-selectin were measured in 37 control subjects and 43 patients (32 with acute myocardial infarction and 11 with unstable angina). Measurements were made at the time of admission and ten days later using commercial enzyme-linked immunoabsorbent assay (ELISA) kits (R&D Systems, UK). RESULTS: There was a significant increase in E-selectin (p < 0.05) in patients with unstable angina at admission and ten days later. In contrast, patients with acute myocardial infarction showed no significant differences in E-selectin compared with the control group at admission or ten days later. A significant increase in VCAM-1 levels was demonstrated in both groups of patients and ICAM-1 levels in acute myocardial infarction, but the concentrations of VCAM-1 and ICAM-1 in both groups of patients at admission and ten days later did not differ significantly. There was no relation between soluble endothelial adhesion molecule levels and the severity of myocardial damage estimated by cardiac enzymes or electrocardiographic changes. CONCLUSION: This study indicates that serum levels of E-selectin, measured at time of admission and ten days later, could be a marker for unstable angina and might be useful in the differential diagnosis with myocardial infarction.     

Simultaneous occurrence of papillary carcinoma, oncocytic carcinoma and malignant lymphoma of the thyroid gland in a female patient with Hashimoto's disease

A 51-year-old woman was admitted for a painless enlargement of the thyroid lasting over 6 months. Hashimoto's thyreoiditis was diagnosed and three tumors were found: oncocytic carcinoma, malignant lymphoma and papillary carcinoma. In the right lobe, oncocytic carcinoma and high grade malignant lymphoma composed of cells with irregular, lobulated nuclei were found. The lymphoma was confined to the thyroid gland. The oncocytic carcinoma invaded the capsule and the surrounding tissues. In the left lobe, there was a papillary carcinoma.     

Effect of Oral Sebacic Acid on Postprandial Glycemia, Insulinemia, and Glucose Rate of Appearance in Type 2 Diabetes

OBJECTIVE

Dicarboxylic acids are natural products with the potential of being an alternate dietary source of energy. We aimed to evaluate the effect of sebacic acid (a 10-carbon dicarboxylic acid; C10) ingestion on postprandial glycemia and glucose rate of appearance (R_a) in healthy and type 2 diabetic subjects. Furthermore, the effect of C10 on insulin-mediated glucose uptake and on GLUT4 expression was assessed in L6 muscle cells in vitro.

RESEARCH DESIGN AND METHODS

Subjects ingested a mixed meal (50% carbohydrates, 15% proteins, and 35% lipids) containing 0 g (control) or 10 g C10 in addition to the meal or 23 g C10 as a substitute of fats.

RESULTS

In type 2 diabetic subjects, the incremental glucose area under the curve (AUC) decreased by 42% (P < 0.05) and 70% (P < 0.05) in the 10 g C10 and 23 g C10 groups, respectively. At the largest amounts used, C10 reduced the glucose AUC in healthy volunteers also. When fats were substituted with 23 g C10, AUC of R_a was significantly reduced on the order of 18% (P < 0.05) in both healthy and diabetic subjects. The insulin-dependent glucose uptake by L6 cells was increased in the presence of C10 (38.7 ± 10.3 vs. 11.4 ± 5.4%; P = 0.026). This increase was associated with a 1.7-fold raise of GLUT4.

CONCLUSIONS

Sebacic acid significantly reduced hyperglycemia after a meal in type 2 diabetic subjects. This beneficial effect was associated with a reduction in glucose R_a, probably due to lowered hepatic glucose output and increased peripheral glucose disposal.The World Health Report launched in 2002 by the World Health Organization advised that more than 1 billion adults worldwide are overweight and at least 300 million are clinically obese. Type 2 diabetes can be considered a threatening obesity-related disease because hyperglycemia causes relevant complications such as micro- and macroangiopathy. Patients with type 2 diabetes exhibit increased hepatic glucose output, which is identified as the main cause of fasting hyperglycemia and is associated with impaired plasma glucose clearance (1) and reduced hepatic synthesis of glycogen of ∼25–45% compared with that in nondiabetic subjects (2). Increased hepatic gluconeogenesis has been considered to be responsible for elevated hepatic glucose output in type 2 diabetes (3). When glycogen is available in adequate amounts, there is an autolimitation of hepatic glucose production. In diabetes, a breakdown of this autoregulation may occur if glycogenolysis is limited by glycogen depletion (4).Jenkins et al. (5) have shown that spreading the nutrient load over a longer period of time by increased meal frequency, the so-called nibbling diet, is beneficial in terms of reduction of circulating levels of glucose, insulin, and free fatty acids in type 2 diabetes. Thus, the availability of snacks poor in fat and that do not induce hyperglycemia and/or overstimulate insulin secretion would be a good tool in the diet of insulin-resistant, type 2 diabetic subjects.Dicarboxylic acids are naturally occurring substances produced by both higher plants and animals via ω-oxidation of fatty acids (6,7). In plants, long-chain dicarboxylic acids are components of natural protective polymers, cutin and suberin, which support biopolyesters involved in waterproofing the leaves and fruits, regulating the flow of nutrients among various plant cells and organs, and minimizing the deleterious impact of pathogens (7). In animals and humans, medium chain dicarboxylic acids, which include prevalently sebacic (C10) and dodecanedioic (C12) acids, derive from the β-oxidation of longer chain dicarboxylic acids (8). Long-chain dicarboxylic acids, in turn, are formed from the correspondent fatty acids by ω-oxidation in the microsomal membranes (9) or are taken in with a diet rich in vegetables (7).We have shown previously that medium-chain dicarboxylic acids represent a suitable alternate energy substrate to glucose in clinical conditions with marked insulin resistance and/or impaired aerobic glycolysis (10). Interestingly, in type 2 diabetes, medium-chain dicarboxylic acids are rapidly oxidized, do not stimulate insulin secretion, and reduce muscle fatigue (11). Nevertheless, the effect of C10 or C12, not as a substitute but in addition to available carbohydrates, on glucose homeostasis has never been studied.On this basis, our aim was to investigate the effect of oral administration of C10 on postprandial glycemia, insulinemia, and glucose rate of appearance (R_a) in type 2 diabetic subjects compared with that in healthy volunteers. To further elucidate the mechanism of action of sebacic acid in diabetes, insulin-mediated glucose uptake and GLUT4 protein expression were assessed in L6 cells in vitro.     

Establishing recommendations for physical medicine and rehabilitation: the SOFMER methodology.

OBJECTIVE: The development of a rigorous methodology based on published results of clinical trials, evaluation of daily practice in France and multidisciplinary expert opinion to elaborate recommendations for rehabilitation interventions. METHODS AND RESULTS: The following describes the methodology of SOFMER (Société Fran?aise de Médecine Physique et de Réadaptation [French Society of Physical Medicine and Rehabilitation]) for developing recommendations for rehabilitation interventions. The test case was developing recommendations for rehabilitation in hip or knee osteoarthritis (OA) and hip or knee arthroplasty. Physicians in rehabilitation, orthopedic surgery and rheumatology identified, synthesized, and analyzed data from the literature by use of the usual French system of grading trials (the French Agency for Accreditation and Evaluation in Healthcare [ANAES] scale). The data were published results of comparative controlled studies such as randomized controlled trials, controlled clinical trials, cohort studies, case control studies, reviews of clinical trials, and case series, as well as uncontrolled cohort studies. The resulting recommendations were presented to the three annual French national congresses of rehabilitation, rheumatology, and orthopedic surgery for comment and for adapting to French professional practice. Finally, a panel of multidisciplinary experts (physicians in physical medicine and rehabilitation, rheumatologists, orthopedic surgeons, general practitioners, physical therapists, social workers, podologists, occupational therapists, nurses, and patients) validated the recommendations. CONCLUSION: The SOFMER methodology could be an interesting tool for use in developing recommendations elaborated by all the concerned medical and surgical specialists in the wide domain of rehabilitation.     

Molecular characterization of VP4 and NSP4 genes from rotavirus strains infecting neonates and young children in Belém, Brazil

Several reports have identified P[6] specificities in humans and in animals in different countries of the world, but few sequence data are available in public databases. In this work we have characterized the VP4 strains bearing P[6] specificity and NSP4 genotypes among diarrheic young children and diarrheic and non-diarrheic neonates from three studies previously conducted in Belém, Northern region of Brazil. As the to VP8* fragment, we observed a close relationship to both human prototypes of lineage P[6]-Ia (bootstrap of 99%) and porcine sublineages Ib and Ic (89.2-98.1% aa similarity and mean of 95%). With regards to the NSP4, the samples clustered into genotypes A and B. Of note, of the 27 P[6] strains analyzed in the present study and classified as genotype B, 8 (29.6%) were more similar to porcine prototypes when VP8* and NSP4 genes are compared, and were recovered, one from a neonate and seven from diarrheic children. These preliminary findings reinforce that further investigations are needed to assess the relative frequencies of P[6] strains in our region, as well as to investigate the potential for interspecies transmission involving humans and animals, particularly pigs.     

Detection of membrane fluidity in submitochondrial particles of platelets and erythrocyte membranes from Mexican patients with Alzheimer disease by intramolecular excimer formation of 1,3 dipyrenylpropane

It has been suggested that mitochondrial dysfunction and defects in membrane structure could be implied in AD pathogenesis. The aim of the present work was the study of membrane fluidity in submitochondrial platelet particles and erythrocyte membranes from Mexican patients. Blood samples were obtained from 30 patients with Alzheimer disease and 30 aged-matched control subjects. Membrane fluidity determinations were done using a very low concentration of the fluorescent dipyrenylpropane probe incorporated in both types of membranes. This probe is able to give excimer and monomer fluorescence, therefore it can be used to monitor fluidity changes in biological membranes. The data obtained showed that in submitochondrial particles from AD patients, the excimer to monomer fluorescent intensity ratio was lower (0.231 +/- 0.008) than aged-matched control subjects (0.363 +/- 0.014). Therefore, membrane fluidity was lower in AD samples. On the other hand, we found similar membrane fluidity in erythrocytes from AD patients and aged-matched controls: the fluorescent intensity ratios were 0.312 +/- 0.03 and 0.305 +/- 0.033, respectively. In addition, lipid peroxidation in submitochondrial particles and erythrocyte membranes was higher in AD samples than in aged-matched controls. These data suggest that submitochondrial platelet particles are more sensitive to oxidative stress than erythrocyte membranes.     

Prevalence of human papillomavirus genotypes in cytologic abnormalities from unvaccinated women living in north-western Spain

Cervical cancer and its precursors low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) are associated with infection by human papillomavirus (HPV), in particular HPV 16 and 18. The distribution of the HPV genotype varies with the severity of cervical disease, age and the geographic location of the patients. We report the results of a population study carried out in a region of north-western (NW) Spain aimed at determining the prevalence of single and multiple infections by 35 types of HPV using low-density microarrays for 113 cases with negative for intraepithelial lesions or malignancies; 588 with atypical squamous cells of undetermined significance (ASCUS)/LSIL; 183 with HSIL; and seven cases of squamous cell carcinomas. Of the 891 patients analysed, 50.2% had single infections and 49.8% had multiple HPV infections. In women aged below 30 years, there was a predominance of multiple infections (p = 0.027). ASCUS/LSIL was associated with multiple and HSIL with single infections (p = 0.025). We observed significant increases in the percentage of infections due to a high-risk (HR) type of HPV when the severity of the cytological lesion increased (p = 0.001). No relationship was found between greater aggressiveness in the cytological diagnosis and a higher number of HPV types involved in multiple infections. The five most frequent genotypes were HPV 16 (26.3%), 53 (18.2%), 51 (17.3%), 6 (14.8%) and 66 (13.1%). The prevalence of HPV 16, 33 and 58 increased significantly from ACUS/LSIL to HSIL and the prevalence of HPV 51, 53 and 66 decreased. HPV 16 was the only genotype that showed a significant increase in prevalence when the severity of the cytological disease increased in single infections (p = 0.0001). The implementation of bivalent prophylactic vaccination could potentially lead to prevention in 32% of the population included in the study - in at least a quarter of patients with ACUS/LSIL (26.7%), and in half of HSIL (50.2%).     

Detection of type II endoleaks in abdominal aortic aneurysms after endovascular repair

Abdominal aortic aneurysm (AAA) is a condition where the weakening of the aortic wall leads to its widening and the generation of a thrombus. To prevent a possible rupture of the aortic wall, AAA can be treated non-invasively by means of the endovascular aneurysm repair technique (EVAR), consisting of placing a stent-graft inside the aorta by a cateter to exclude the aneurysm sac from the blood circulation. A major complication is the presence of liquid blood turbulences, called endoleaks, in the thrombus formed in the space between the aortic wall and the stent-graft. In this paper we propose an automatic method for the detection of type II endoleaks in computer tomography angiography (CTA) images. The lumen and thrombus in the aneurysm area are first segmented using a radial model approach. Then, these regions are split into Thrombus Connected Components (TCCs) using a watershed-based segmentation and geometric and image content-based characteristics are obtained for each TCC. Finally, TCCs are classified into endoleaks and non-endoleaks using a multilayer Perceptron (MLP) trained on manual labeled sample TCCs provided by experts.