Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the breast international group 1-98 trial

To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up.

Copeptin adds prognostic information after ischemic stroke: Results from the CoRisk study

To evaluate and validate the incremental value of copeptin in the prediction of outcome and complications as compared with established clinical variables.

The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients

Chronic hepatitis C infection is a major cause of end-stage liver disease. Therapy outcome is influenced by 25-OH vitamin D deficiency. To further address this observation, our study investigates the impact of the vitamin D receptor (NR1I1) haplotype and combined effects of plasma vitamin D levels in a well-described cohort of hepatitis C patients.

The Effects of Prenatal Exposure to Altered Melatonin Levels on Hippocampal Gene Expression in the Male Rat

The stability of the circadian rhythm for mammals depends on the levels of serotonin and melatonin, neurohormones that signal for lightness and darkness, respectively. Disruption in the stability of neurohormones has been shown to be a critical factor in psychopathological disorders in humans. For example, altering levels of melatonin in utero through administration of melatonin or the melatonin receptor antagonist, luzindole, has been shown to cause changes in developmental growth and adult behavior in the male rat. Analysis of relative adult hippocampal gene expression with RT-PCR revealed differences in ARNTL expression that suggested abnormality in clock gene expression of the rats that were prenatally exposed to altered levels of melatonin. Differences in the degree of plasticity as suggested by previous behavior testing did not result in differences in gene expression for GABA receptors or NMDA receptors. Morevoer, growth associated protein 43, GAP-43, a protein that is necessary for neuronal growth cones as well as long term learning has been found to be critical for axon and presynaptic terminal formation and retention in other studies, but hippocampal gene expression in our study showed no significant alteration after exposure to various maternal melatonin levels. However, ARNTL is a key regulatory component of clock genes and the circadian cycle so that alterations in the expression of thi critical gene may lead to critical changes in neuronal growth and plasticity. Our data support the conclusion that the manipulation of maternal melatonin levels alters the brain development and the circadian cycles that may lead to physiological and behavioral abnormalities in adult offspring.

Peri-interventional antibiotic prophylaxis only vs continuous low-dose antibiotic treatment in patients with JJ stents: a prospective randomised trial analysing the effect on urinary tract infections and stent-related symptoms

To evaluate the antibiotic treatment regime in patients with indwelling JJ stents, the benefits and disadvantages of a peri-interventional antibiotic prophylaxis were compared with those of a continuous low-dose antibiotic treatment in a prospective randomised trial.

Angiotensinergic innervation of the kidney: Localization and relationship with catecholaminergic postganglionic and sensory nerve fibers

We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, catecholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion.

Acute aortic dissection determines the fate of initially untreated aortic segments in Marfan syndrome

The aim of the current study was to investigate incidence and causes of surgical interventions in primarily nontreated aortic segments after previous aortic repair in patients with Marfan syndrome.

The assessment of cognition in visually impaired older adults

Background: visual and cognitive impairments are common in later life. Yet there are very few cognitive screening tests for the visually impaired. Objective: to screen for cognitive impairment in the visually impaired. Methods: case-control study including 150 elderly participants with visual impairment (n = 74) and a control group without visual impairment (n = 76) using vision-independent cognitive tests and cognitive screening tests (MMSE and clock drawing tests (CDT)) which are in part vision dependent. Results: the scoring of the two groups did not differ in the vision-independent cognitive tests. Visually impaired patients performed poorer than controls in the vision-dependent items of the MMSE (T = 7.3; df: 148; P < 0.001) and in CDT (T = 3.1; df: 145; P = 0.003). No group difference was found when vision-independent items were added to MMSE and CDT. The test score gain by the use of vision-independent items correlated with the severity of visual impairment (P < 0.002). Conclusion: visually impaired patients benefit from cognitive tests, which do not rely on vision. The more visually impaired the greater the benefit.

Comparison of the gene expression profiles from normal and Fgfrl1 deficient mouse kidneys reveals downstream targets of Fgfrl1 signaling

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron.

Does surgery improve outcomes for esophageal squamous cell carcinoma? An analysis using the surveillance epidemiology and end results registry from 1998 to 2008

We examined survival associated with locally advanced esophageal squamous cell cancer (SCC) to evaluate if treatment without surgery could be considered adequate.

The role of radiation therapy in resected T2 N0 esophageal cancer: a population-based analysis

The prognosis of even early-stage esophageal cancer is poor. Because there is not a consensus on how to manage T2 N0 disease, we examined survival after resection of T2 N0 esophageal cancer, with or without radiation therapy.

Fgfrl1, a fibroblast growth factor receptor-like gene, is found in the cephalochordate Branchiostoma floridae but not in the urochordate Ciona intestinalis

FGFRL1 is a novel member of the fibroblast growth factor receptor family that controls the formation of musculoskeletal tissues. Some vertebrates, including man, cow, dog, mouse, rat and chicken, possess a single copy the FGFRL1 gene. Teleostean fish have two copies, fgfrl1a and fgfrl1b, because they have undergone a whole genome duplication. Vertebrates belong to the chordates, a phylum that also includes the subphyla of the cephalochordates (e.g. Branchiostoma floridae) and urochordates (tunicates, e.g. Ciona intestinalis). We therefore investigated whether other chordates might also possess an FGFRL1 related gene. In fact, a homologous gene was found in B. floridae (amphioxus). The corresponding protein showed 60% sequence identity with the human protein and all sequence motifs identified in the vertebrate proteins were also conserved in amphioxus Fgfrl1. In contrast, the genome of the urochordate C. intestinalis and those from more distantly related invertebrates including the insect Drosophila melanogaster and the nematode Caenorhabditis elegans did not appear to contain any related sequences. Thus, the FGFRL1 gene might have evolved just before branching of the vertebrate lineage from the other chordates.

Pilot study on the comprehensive economic costs of major trauma: Consequential costs are well in excess of medical costs

BACKGROUND: Trauma care is expensive. However, reliable data on the exact lifelong costs incurred by a major trauma patient are lacking. Discussion usually focuses on direct medical costs--underestimating consequential costs resulting from absence from work and permanent disability. METHODS: Direct medical costs and consequential costs of 63 major trauma survivors (ISS >13) at a Swiss trauma center from 1995 to 1996 were assessed 5 years posttrauma. The following cost evaluation methods were used: correction cost method (direct cost of restoring an original state), human capital method (indirect cost of lost productivity), contingent valuation method (human cost as the lost quality of life), and macroeconomic estimates. RESULTS: Mean ISS (Injury Severity Score) was 26.8 +/- 9.5 (mean +/- SD). In all, 22 patients (35%) were disabled, causing discounted average lifelong total costs of USD 1,293,800, compared with 41 patients (65%) who recovered without any disabilities with incurred costs of USD 147,200 (average of both groups USD 547,800). Two thirds of these costs were attributable to a loss of production whereas only one third was a result of the cost of correction. Primary hospital treatment (USD 27,800 +/- 37,800) was only a minor fraction of the total cost--less than the estimated cost of police and the judiciary. Loss of quality of life led to considerable intangible human costs similar to real costs. CONCLUSIONS: Trauma costs are commonly underestimated. Direct medical costs make up only a small part of the total costs. Consequential costs, such as lost productivity, are well in excess of the usual medical costs. Mere cost averages give a false estimate of the costs incurred by patients with/without disabilities.