Effect of long-term administration of cross-sex hormone therapy on serum and urinary uric acid in transsexual persons.

BACKGROUND. Transsexual persons afford a very suitable model to study the effect of sex steroids on uric acid metabolism. DESIGN. This was a prospective study to evaluate the uric acid levels and fractional excretion of uric acid (FEUA) in a cohort of 69 healthy transsexual persons, 22 male-to-female transsexuals (MFTs) and 47 female-to-male transsexuals (FMTs).The subjects were studied at baseline and 1 and 2 yr after starting cross-sex hormone treatment. RESULTS. The baseline levels of uric acid were higher in the MFT group.Compared with baseline, uric acid levels had fallen significantly after 1 yr of hormone therapy in the MFT group and had risen significantly in the FMT group. The baseline FEUA was greater in the FMT group. After 2 yr of cross-sex hormone therapy, the FEUA had increased in MFTs (P = 0.001) and fallen in FMTs (P = 0.004).In MFTs, the levels of uric acid at 2 yr were lower in those who had received higher doses of estrogens (P = 0.03),and the FEUA was higher (P = 0.04).The FEUA at 2 yr was associated with both the estrogen dose (P = 0.02) and the serum levels of estradiol-17beta (P =0.03).In MFTs, a correlation was found after 2 yr of therapy between the homeostasis model assessment of insulin resistance and the serum uric acid (r = 0.59; P = 0.01). CONCLUSIONS. Serum levels of uric acid and the FEUA are altered in transsexuals as a result of cross-sex hormone therapy.The results concerning the MFT group support the hypothesis that the lower levels of uric acid in women are due to estrogen-induced increases in FEUA.

Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1.

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.

Nutrición, fibrosis quística y aparato digestivo

The prevalence of hyponutrition in cystic fibrosis is high although it may vary according to the different studies. Detection of hyponutrition should be done by combining different methods, depending on their availability. However, the simplest and most validated criterion is to measure at each visit the weight (and height in children) in order to calculate the body mass index and categorizing hyponutrition according to absolute criteria: in adults < 18.5 kg/m(2), and in children as percentiles of the body mass index. Worsening of the nutritional status is directly related with the decrease in lung function parameters and it has been proposed as a morbidity (and even mortality) predictive factor in people with cystic fibrosis, independently of the level of pulmonary dysfunction. Exocrine pancreatic insufficiency is present is approximately 70-90% of the patients with cystic fibrosis and the genotype-phenotype correlation is high. Most of the patients with exocrine pancreatic insufficiency tolerate a high-fat diet provided that they are treated with pancreatic enzymes at appropriate doses. The prevalence of diabetes increases with age, reaching up 40% of the cases in patients older than 30 years. Clinical liver involvement is less prevalent (it approximately affects 1/3 of the patients). Other intestinal complications such as meconial ileus, gastroesophageal reflux, obstruction of the distal intestine, or fibrosing colon disease may also condition malnourishment. In patients with cystic fibrosis, a usual high-fat diet providing 120%-150% of the recommended calories is advised. If the nutritional goals are not achieved or maintained with diet modifications, artificial supplements may be added, although the recommendation for their use has not been endorsed by solid scientific evidences. The most frequently used preparations usually are polymeric or hypercaloric. The indications for enteral (through a tube, especially gastrostomy) or parenteral nutritional support are similar to those used in other pathologies. Dietary and nutritional control should be included in a multidisciplinary program allowing the improvement of the functional capacity and the quality of life and reducing, at least from a theoretical viewpoint, the morbimortality associated to malnourishment in these patients.

Prevention of the renarrowing of coronary arteries using drug-eluting stents in the perioperative period: an update.

The management of patients scheduled for surgery with a coronary stent, and receiving 1 or more antiplatelet drugs, has many controversies. The premature discontinuation of antiplatelet drugs substantially increases the risk of stent thrombosis (ST), myocardial infarction, and cardiac death, and surgery under an altered platelet function could also lead to an increased risk of bleeding in the perioperative period. Because of the conflict in the recommendations, this article reviews the current antiplatelet protocols after positioning a coronary stent, the evidence of increased risk of ST associated with the withdrawal of antiplatelet drugs and increased bleeding risk associated with its maintenance, the different perioperative antiplatelet protocols when patients are scheduled for surgery or need an urgent operation, and the therapeutic options if excessive bleeding occurs.

Proceso INFORNUT: validación de la fase de filtro-FILNUT--y comparación con otros métodos de detección precoz de desnutrición hospitalaria.

INTRODUCTION According to several series, hospital hyponutrition involves 30-50% of hospitalized patients. The high prevalence justifies the need for early detection from admission. There several classical screening tools that show important limitations in their systematic application in daily clinical practice. OBJECTIVES To analyze the relationship between hyponutrition, detected by our screening method, and mortality, hospital stay, or re-admissions. To analyze, as well, the relationship between hyponutrition and prescription of nutritional support. To compare different nutritional screening methods at admission on a random sample of hospitalized patients. Validation of the INFORNUT method for nutritional screening. MATERIAL AND METHODS In a previous phase from the study design, a retrospective analysis with data from the year 2003 was carried out in order to know the situation of hyponutrition in Virgen de la Victoria Hospital, at Malaga, gathering data from the MBDS (Minimal Basic Data Set), laboratory analysis of nutritional risk (FILNUT filter), and prescription of nutritional support. In the experimental phase, a cross-sectional cohort study was done with a random sample of 255 patients, on May of 2004. Anthropometrical study, Subjective Global Assessment (SGA), Mini-Nutritional Assessment (MNA), Nutritional Risk Screening (NRS), Gassull's method, CONUT and INFORNUT were done. The settings of the INFORNUT filter were: albumin < 3.5 g/dL, and/or total proteins <5 g/dL, and/or prealbumin <18 mg/dL, with or without total lymphocyte count < 1.600 cells/mm3 and/or total cholesterol <180 mg/dL. In order to compare the different methods, a gold standard is created based on the recommendations of the SENPE on anthropometrical and laboratory data. The statistical association analysis was done by the chi-squared test (a: 0.05) and agreement by the k index. RESULTS In the study performed in the previous phase, it is observed that the prevalence of hospital hyponutrition is 53.9%. One thousand six hundred and forty four patients received nutritional support, of which 66.9% suffered from hyponutrition. We also observed that hyponutrition is one of the factors favoring the increase in mortality (hyponourished patients 15.19% vs. non-hyponourished 2.58%), hospital stay (hyponourished patients 20.95 days vs. non-hyponourished 8.75 days), and re-admissions (hyponourished patients 14.30% vs. non-hyponourished 6%). The results from the experimental study are as follows: the prevalence of hyponutrition obtained by the gold standard was 61%, INFORNUT 60%. Agreement levels between INFORNUT, CONUT, and GASSULL are good or very good between them (k: 0.67 INFORNUT with CONUT, and k: 0.94 INFORNUT and GASSULL) and wit the gold standard (k: 0.83; k: 0.64 CONUT; k: 0.89 GASSULL). However, structured tests (SGA, MNA, NRS) show low agreement indexes with the gold standard and laboratory or mixed tests (Gassull), although they show a low to intermediate level of agreement when compared one to each other (k: 0.489 NRS with SGA). INFORNUT shows sensitivity of 92.3%, a positive predictive value of 94.1%, and specificity of 91.2%. After the filer phase, a preliminary report is sent, on which anthropometrical and intake data are added and a Nutritional Risk Report is done. CONCLUSIONS Hyponutrition prevalence in our study (60%) is similar to that found by other authors. Hyponutrition is associated to increased mortality, hospital stay, and re-admission rate. There are no tools that have proven to be effective to show early hyponutrition at the hospital setting without important applicability limitations. FILNUT, as the first phase of the filter process of INFORNUT represents a valid tool: it has sensitivity and specificity for nutritional screening at admission. The main advantages of the process would be early detection of patients with risk for hyponutrition, having a teaching and sensitization function to health care staff implicating them in nutritional assessment of their patients, and doing a hyponutrition diagnosis and nutritional support need in the discharge report that would be registered by the Clinical Documentation Department. Therefore, INFORNUT would be a universal screening method with a good cost-effectiveness ratio.

Influence of physical activity and dietary habits on lipid profile, blood pressure and BMI in subjects with metabolic syndrome

BACKGROUND The present study was determined the influence of physical activity and dietary habits on lipid profile, blood pressure (BP) and body mass index (BMI) in subjects with metabolic syndrome (MS). AIMS Identify the relationship between physical activity and proper nutrition and the probability of suffering from myocardial infarction (MI). METHODS Hundred chronically ill with MS who were active and followed a healthy diet were classified as compliant, while the remaining subjects were classified as non-compliant. RESULTS The compliant subjects show lower BMI values (30.8±4.9 vs 32.5±4.6), as well as lower levels of triacylglycerol (130.4±48.2 vs 242.1±90.1), total cholesterol (193.5±39 vs 220.2±52.3) and low-density lipoprotein cholesterol (105.2±38.3 vs 139.2±45). They show higher values in terms of high-density lipoprotein cholesterol levels (62.2±20.1 vs 36.6±15.3), with statistically significant differences. In terms of both systolic and diastolic pressure, no differences were revealed between the groups; however, those who maintain proper dietary habits show lower systolic blood pressure levels than the inactive subjects. The probability of suffering from MI greatly increases among the group of non-compliant subjects. CONCLUSIONS Our results demonstrate how performing aerobic physical activity and following an individualized, Mediterranean diet significantly reduces MS indicators and the chances of suffering from MI.

Thin healthy women have a similar low bone mass to women with anorexia nervosa.

An association between anorexia nerviosa (AN) and low bone mass has been demonstrated. Bone loss associated with AN involves hormonal and nutritional impairments, though their exact contribution is not clearly established. We compared bone mass in AN patients with women of similar weight with no criteria for AN, and a third group of healthy, normal-weight, age-matched women. The study included forty-eight patients with AN, twenty-two healthy eumenorrhoeic women with low weight (LW group; BMI < 18.5 kg/m2) and twenty healthy women with BMI >18.5 kg/m2 (control group), all of similar age. We measured lean body mass, percentage fat mass, total bone mineral content (BMC) and bone mineral density in lumbar spine (BMD LS) and in total (tBMD). We measured anthropometric parameters, leptin and growth hormone. The control group had greater tBMD and BMD LS than the other groups, with no differences between the AN and LW groups. No differences were found in tBMD, BMD LS and total BMC between the restrictive (n 25) and binge-purge type (n 23) in AN patients. In AN, minimum weight (P = 0.002) and percentage fat mass (P = 0.02) explained BMD LS variation (r2 0.48) and minimum weight (r2 0.42; P = 0.002) for tBMD in stepwise regression analyses. In the LW group, BMI explained BMD LS (r2 0.72; P = 0.01) and tBMD (r2 0.57; P = 0.04). We concluded that patients with AN had similar BMD to healthy thin women. Anthropometric parameters could contribute more significantly than oestrogen deficiency in the achievement of peak bone mass in AN patients.

Decreased levels of uric acid after oral glucose challenge is associated with triacylglycerol levels and degree of insulin resistance

Hyperuricaemia is one of the components of metabolic syndrome. Both oxidative stress and hyperinsulinism are important variables in the genesis of this syndrome and have a close association with uric acid (UA). We evaluated the effect of an oral glucose challenge on UA concentrations. The study included 656 persons aged 18 to 65 years. Glycaemia, insulin, UA and plasma proteins were measured at baseline and 120 min after an oral glucose tolerance test (OGTT). The baseline sample also included measurements of total cholesterol, triacylglycerol (TAG) and HDL-cholesterol. Insulin resistance was calculated with the homeostasis model assessment. UA levels were significantly lower after the OGTT (281.93 (sd 92.19) v. 267.48 (sd 90.40) micromol/l; P < 0.0001). Subjects with a drop in UA concentrations >40.86 micromol/l (>75th percentile) had higher plasma TAG levels (P = 0.0001), baseline insulin (P = 0.02) and greater insulin resistance (P = 0.034). Women with a difference in plasma concentrations of UA above the 75th percentile had higher baseline insulin levels (P = 0.019), concentration of plasma TAG (P = 0.0001) and a greater insulin resistance index (P = 0.029), whereas the only significant difference in men was the level of TAG. Multiple regression analysis showed that the basal TAG levels, insulin at 120 min, glycaemia at 120 min and waist:hip ratio significantly predicted the variance in the UA difference (r2 0.077). Levels of UA were significantly lower after the OGTT and the individuals with the greatest decrease in UA levels are those who have greater insulin resistance and higher TAG levels.

Alterations of specific biomarkers of metabolic pathways in vascular tree from patients with Type 2 diabetes.

The aims of this study were to check whether different biomarkers of inflammatory, apoptotic, immunological or lipid pathways had altered their expression in the occluded popliteal artery (OPA) compared with the internal mammary artery (IMA) and femoral vein (FV) and to examine whether glycemic control influenced the expression of these genes. The study included 20 patients with advanced atherosclerosis and type 2 diabetes mellitus, 15 of whom had peripheral arterial occlusive disease (PAOD), from whom samples of OPA and FV were collected. PAOD patients were classified based on their HbA1c as well (HbA1c ≤ 6.5) or poorly (HbA1c > 6.5) controlled patients. Controls for arteries without atherosclerosis comprised 5 IMA from patients with ischemic cardiomyopathy (ICM). mRNA, protein expression and histological studies were analyzed in IMA, OPA and FV. After analyzing 46 genes, OPA showed higher expression levels than IMA or FV for genes involved in thrombosis (F3), apoptosis (MMP2, MMP9, TIMP1 and TIM3), lipid metabolism (LRP1 and NDUFA), immune response (TLR2) and monocytes adhesion (CD83). Remarkably, MMP-9 expression was lower in OPA from well-controlled patients. In FV from diabetic patients with HbA1c ≤6.5, gene expression levels of BCL2, CDKN1A, COX2, NDUFA and SREBP2 were higher than in FV from those with HbA1c >6.5. The atherosclerotic process in OPA from diabetic patients was associated with high expression levels of inflammatory, lipid metabolism and apoptotic biomarkers. The degree of glycemic control was associated with gene expression markers of apoptosis, lipid metabolism and antioxidants in FV. However, the effect of glycemic control on pro-atherosclerotic gene expression was very low in arteries with established atherosclerosis.

VEGF gene expression in adult human thymus fat: a correlative study with hypoxic induced factor and cyclooxygenase-2.

It is well known that the adult human thymus degenerates into fat tissue; however, it has never been considered as a potential source of angiogenic factors. Recently, we have described that this fat (TAT) produces angiogenic factors and induces human endothelial cell proliferation and migration, indicating its potential angiogenic properties. DESIGN Adult thymus fat and subcutaneous adipose tissue specimens were obtained from 28 patients undergoing cardiac surgery, making this tissue readily available as a prime source of adipose tissue. We focused our investigation on determining VEGF gene expression and characterizing the different genes, mediators of inflammation and adipogenesis, and which are known to play a relevant role in angiogenesis regulation. RESULTS We found that VEGF-A was the isoform most expressed in TAT. This expression was accompanied by an upregulation of HIF-1alpha, COX-2 and HO-1 proteins, and by increased HIF-1 DNA binding activity, compared to SAT. Furthermore, we observed that TAT contains a high percentage of mature adipocytes, 0.25% of macrophage cells, 15% of endothelial cells and a very low percentage of thymocyte cells, suggesting the cellular variability of TAT, which could explain the differences in gene expression observed in TAT. Subsequently, we showed that the expression of genes known as adipogenic mediators, including PPARgamma1/gamma2, FABP-4 and adiponectin was similar in both TAT and SAT. Moreover the expression of these latter genes presented a significantly positive correlation with VEGF, suggesting the potential association between VEGF and the generation of adipose tissue in adult thymus. CONCLUSION Here we suggest that this fat has a potential angiogenic function related to ongoing adipogenesis, which substitutes immune functions within the adult thymus. The expression of VEGF seems to be associated with COX-2, HO-1 and adipogenesis related genes, suggesting the importance that this new fat has acquired in research in relation to adipogenesis and angiogenesis.

Adipose tissue gene expression of factors related to lipid processing in obesity.

BACKGROUND Adipose tissue lipid storage and processing capacity can be a key factor for obesity-related metabolic disorders such as insulin resistance and diabetes. Lipid uptake is the first step to adipose tissue lipid storage. The aim of this study was to analyze the gene expression of factors involved in lipid uptake and processing in subcutaneous (SAT) and visceral (VAT) adipose tissue according to body mass index (BMI) and the degree of insulin resistance (IR). METHODS AND PRINCIPAL FINDINGS VLDL receptor (VLDLR), lipoprotein lipase (LPL), acylation stimulating protein (ASP), LDL receptor-related protein 1 (LRP1) and fatty acid binding protein 4 (FABP4) gene expression was measured in VAT and SAT from 28 morbidly obese patients with Type 2 Diabetes Mellitus (T2DM) or high IR, 10 morbidly obese patients with low IR, 10 obese patients with low IR and 12 lean healthy controls. LPL, FABP4, LRP1 and ASP expression in VAT was higher in lean controls. In SAT, LPL and FABP4 expression were also higher in lean controls. BMI, plasma insulin levels and HOMA-IR correlated negatively with LPL expression in both VAT and SAT as well as with FABP4 expression in VAT. FABP4 gene expression in SAT correlated inversely with BMI and HOMA-IR. However, multiple regression analysis showed that BMI was the main variable contributing to LPL and FABP4 gene expression in both VAT and SAT. CONCLUSIONS Morbidly obese patients have a lower gene expression of factors related with lipid uptake and processing in comparison with healthy lean persons.

Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity.

BACKGROUND Extreme weight conditions (EWC) groups along a continuum may share some biological risk factors and intermediate neurocognitive phenotypes. A core cognitive trait in EWC appears to be executive dysfunction, with a focus on decision making, response inhibition and cognitive flexibility. Differences between individuals in these areas are likely to contribute to the differences in vulnerability to EWC. The aim of the study was to investigate whether there is a common pattern of executive dysfunction in EWC while comparing anorexia nervosa patients (AN), obese subjects (OB) and healthy eating/weight controls (HC). METHODS Thirty five AN patients, fifty two OB and one hundred thirty seven HC were compared using the Wisconsin Card Sorting Test (WCST); Stroop Color and Word Test (SCWT); and Iowa Gambling Task (IGT). All participants were female, aged between 18 and 60 years. RESULTS There was a significant difference in IGT score (F(1.79); p<.001), with AN and OB groups showing the poorest performance compared to HC. On the WCST, AN and OB made significantly more errors than controls (F(25.73); p<.001), and had significantly fewer correct responses (F(2.71); p<.001). Post hoc analysis revealed that the two clinical groups were not significantly different from each other. Finally, OB showed a significant reduced performance in the inhibition response measured with the Stroop test (F(5.11); p<.001) compared with both AN and HC. CONCLUSIONS These findings suggest that EWC subjects (namely AN and OB) have similar dysfunctional executive profile that may play a role in the development and maintenance of such disorders.

Bosentan and oral anticoagulants in HIV patients: what we can learn of cases reported so far.

Pulmonary arterial hypertension is an infrequent but nevertheless serious life-threatening severe complication of HIV infection. It can be treated with bosentan and oral anticoagulants. Bosentan could induce the acenocoumarol metabolism and it increases the INR values. Until now, no study of interaction between bosentan and oral anticoagulants in HIV patients has reported. So we present a case of this interaction between these drugs and we reviewed MEDLINE to identify all the papers published so far. In our case, several weeks after increasing dose of bosentan acenocoumarol dose had to be progressively increased to 70 mg/week (+33%) without obtaining an adequate INR level (2.0-3.0). Forty-nine days later, we achieved a therapeutic INR with 90 mg/week of warfarin. The use of bosentan and oral anticoagulants together in these patients require a closer monitoring during first weeks of treatment, after increasing the bosentan dose and even during longer periods of time.

Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations

Summary Points Brucellosis remains the commonest anthropozoonosis worldwide, and its treatment remains complex, requiring protracted administration of more than one antibiotic. In November 2006, a consensus meeting aimed at reaching a common specialist statement on the treatment of brucellosis was held in Ioannina, Greece under the auspices of the International Society of Chemotherapy and the Institute of Continuing Medical Education of Ioannina. The author panel suggests that the optimal treatment of uncomplicated brucellosis should be based on a six-week regimen of doxycycline combined either with streptomycin for 2–3 weeks, or rifampicin for six weeks. Gentamicin may be considered an acceptable alternative to streptomycin, while all other regimens/combinations should be considered second-line. The development of a common global therapeutic language for human brucellosis, and future, properly conducted clinical trials would definitely solve controversies regarding the disease.

Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans.

Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.