title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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The base rate of effort test failure in patients with medically unexplained symptoms. | "Effort tests" (i.e., tests that indicate whether appropriate effort is being made) are increasingly used in neuropsychological assessments. However, not all failures on effort tests are necessarily attributable to lack of effort. Understanding the factors that contribute to failure on effort tests has important clinical implications. This study aimed (a) to establish the extent to which patients with medically unexplained symptoms (MUS) presenting to neurology fail effort tests, (b) examine the performance of "mild" and "strong" simulators on effort tests, and (c) compare the performance of simulators and MUS patients. Forty-three MUS patients, 35 mild simulators, and 39 strong simulators undertook a battery of effort tests. The groups were matched for age, estimated IQ, and gender. The MUS patients were not involved in litigation. The failure rate (defined as failing two or more effort tests) was 11% in the MUS group, 94% in the mild simulation groups, and 100% in the strong simulation group. A minority of nonlitigant MUS patients who present to neurology fail effort tests. Possible reasons for this are discussed. In that they do not produce below-chance performance (in contrast with many of the simulators), there is no clear indication of deliberate failure, though this cannot be ruled out. The very high failure rate in the mild simulation group (who were instructed not to overact) indicates the sensitivity of effort tests to lack of effort and the value of including such tests in neuropsychological assessments. | 18,805,240 |
Mitral valve motion after performing an edge-to-edge repair in an isolated swine heart. | Mitral valve motion after performing an edge-to-edge repair is a major concern, but it has not yet been observed directly. Mitral valve motion was assessed by using a high-speed digital video camera and microsonometric analysis in an isolated swine heart, and any changes in the mitral valve area or the development of mitral stenosis symptoms were evaluated. A temporary edge-to-edge repair model was created. The mitral valve motion was assessed by using a high-speed digital video camera, and the motion of the mitral annulus was measured by means of sonomicrometric analysis with or without performing edge-to-edge repair (n = 5). The left ventricular volumetric measurements were also measured with a conductance catheter. One cardiac cycle was divided into 4 phases: the mitral valve open phase, the isovolumic contraction phase, the aortic valve open phase, and the isovolumic relaxation phase. The mitral valve was divided into 2 orifices by using the edge-to-edge technique, and the mitral valve area decreased by approximately 30%. The ratio of mitral valve open phase significantly decreased (31.9% +/- 3.4% vs 41.4% +/- 3.7%, P = .04). There were no significant differences in the diameter and the changes of anteroposterior dimensions of the mitral annulus. The stroke volume and the peak positive and negative dp/dt values showed no obvious change, but dv/dt values increased slightly without significance after removing the edge-to-edge suture (118 +/- 25 vs 130 +/- 17 mL/s, P = .14). The mitral valve area decreased slightly; however, edge-to-edge repair did not create symptomatic mitral stenosis and showed no adverse affects on cardiac function. | 18,805,256 |
New targets for drug development in asthma. | Asthma is a chronic inflammatory disease that affects about 300 million people worldwide, a total that is expected to rise to about 400 million over the next 15-20 years. Most asthmatic individuals respond well to the currently available treatments of inhaled corticosteroids and beta-adrenergic agonists; however, 5-10% have severe disease that responds poorly. Improved knowledge of asthma mechanisms has led to the recognition of different asthma phenotypes that might reflect distinct types of inflammation, explaining the effectiveness of anti-leucotrienes and the anti-IgE monoclonal antibody omalizumab in some patients. However, more knowledge of the inflammatory mechanisms within the airways is required. Improvements in available therapies-such as the development of fast-onset, once-a-day combination drugs with better safety profiles-will occur. Other drugs, such as inhaled p38 MAPK inhibitors and anti-oxidants, that target specific pathways or mediators could prove useful as monotherapies, but could also, in combination with corticosteroids, reduce the corticosteroid insensitivity often seen in severe asthma. Biological agents directed against the interleukin-13 pathway and new immunoregulatory agents that modulate functions of T-regulatory and T-helper-17 cells are likely to be successful. Patient-specific treatments will depend on the development of discriminatory handprints of distinct asthma subtypes and are probably over the horizon. Although a cure is unlikely to be developed in the near future, a greater understanding of disease mechanisms could bring such a situation nearer to reality. | 18,805,336 |
Pontocerebellar hypoplasia type 1. | Pontocerebellar hypoplasias are heterogeneous disorders that share a reduction in the size of brainstem and cerebellum. We describe a patient with features of the rare combination of pontocerebellar hypoplasia and spinal motor neuron disease. Parental consanguinity, low Apgar scores, facial weakness, dysphagia, tongue fasciculations, stridor, generalized hypotonia, severe muscle weakness, areflexia, and congenital joint contractures were evident. Cranial magnetic resonance imaging revealed a small cerebellum and brainstem, and a muscle biopsy revealed neurogenic changes. These abnormalities suggested pontocerebellar hypoplasia type 1. | 18,805,371 |
A simple assay for hyaluronidase activity using fluorescence polarization. | Hyaluronan is a large glycosaminoglycan and is a major constituent of the extracellular matrix, interacting with cell surface receptors such as CD44. We previously reported that fragmented hyaluronan, with the size frequently detected in cancer patients, induces CD44 cleavage and concomitantly enhances tumor cell migration. Although hyaluronan degradation to smaller fragments has been revealed to be a key reaction in regulating cancer progression, simple methods for continuously detecting hyaluronidase activity have not been established. Here, we show that fluorescently-labeled hyaluronan serves as a substrate for continuous assay of hyaluronidase activity. A very simple assay was established to measure degradation of hyaluronan based on fluorescence polarization. The developed assay method would provide a way for continuous measurement of cellular hyaluronidase activity and also for measurement of binding of hyaluronan to its receptors, and thus should be useful for investigation of the function of hyaluronan in cancer progression. | 18,805,398 |
The promiscuity of ARF interactions with the proteasome. | The tumor suppressor ARF is one of the most important oncogenic stress sensors in mammalian cells. Its effect is exerted through the interaction with different cellular partners, often resulting in their functional inactivation. This review focuses on the role played by the proteasome in ARF regulation of protein turnover and the function of most of its interacting partners. Specific proteasome components appear to be involved in the regulation of ARF turnover, bringing to light a complex network of interactions between ARF and the proteasome. | 18,805,416 |
Marked differences between atrial and ventricular gene-expression remodeling in dogs with experimental heart failure. | Congestive heart failure (CHF) causes arrhythmogenic, structural and contractile remodeling, with important atrial-ventricular differences: atria show faster and greater inflammation, cell-death and fibrosis. The present study assessed time-dependent left atrial (LA) and ventricular (LV) gene-expression changes in CHF. Groups of dogs were submitted to ventricular tachypacing (VTP, 240 bpm) for 24 h or 2 weeks, and compared to sham-instrumented animals. RNA from isolated LA and LV cardiomyocytes of each dog was analyzed by canine-specific microarrays (>21,700 probe-sets). LA showed dramatic gene-expression changes, with 4785 transcripts significantly-altered (Q<5) at 24-hour and 6284 at 2-week VTP. LV gene-changes were more limited, with 52 significantly-altered at 24-hour and 130 at 2-week VTP. Particularly marked differences were seen in ECM genes, with 153 changed in LA (e.g. approximately 65-fold increase in collagen-1) at 2-week VTP versus 2 in LV; DNA/RNA genes (LA=358, LV=7); protein biosynthesis (LA=327, LV=14); membrane transport (LA=230, LV=8); cell structure and mobility (LA=159, LV=6) and coagulation/inflammation (LA=147, LV=1). Noteworthy changes in LV were genes involved in metabolism (35 genes; creatine-kinase B increased 8-fold at 2-week VTP) and Ca(2+)-signalling. LA versus LV differential gene-expression decreased over time: 1567 genes were differentially expressed (Q<1) at baseline, 1499 at 24-hour and 897 at 2-week VTP. Pathway analysis revealed particularly-important changes in LA for mitogen-activated protein-kinase, apoptotic, and ubiquitin/proteasome systems, and LV for Krebs cycle and electron-transfer complex I/II genes. VTP-induced CHF causes dramatically more gene-expression changes in LA than LV, dynamically altering the LA-LV differential gene-expression pattern. These results are relevant to understanding chamber-specific remodeling in CHF. | 18,805,423 |
Molecular cloning, tissue distribution and expression profiles of thyroid hormone receptors during embryogenesis in orange-spotted grouper (Epinephelus coioides). | Three distinct thyroid hormone receptor (TR) cDNAs (gTRalphaA, gTRalphaB and gTRbeta) were cloned and sequenced in orange-spotted grouper (Epinephelus coioides). The cDNA of gTRalphaA consisted of 1555-bp and encoded a putative protein of 416 amino acids, while the cDNA of gTRalphaB consisted of 1459-bp and encoded 398 amino acids. The cDNA of gTRbeta is 1470-bp in length and encoded 395 amino acids. The cDNAs of gTRalphaA and gTRalphaB had 68.7% identity in nucleotide sequence and 83.9% identity in deduced amino acid sequence, and shared 57.8%, 57.9% identity in nucleotide sequence and 76.5%, 76.6% in deduced amino acid sequence with gTRbeta, respectively. mRNA expression of gTR was determined by using real-time RT-PCR. The zygotic mRNA expression of gTRalphaA, gTRalphaB and gTRbeta was already presented at the blastula stage, and decreased by gastrulation and body segment appearance. Both gTRalphaA and gTRbeta mRNAs dramatically increased by brain vesicle appearance and lens formation stages, whereas the magnitude of the increase of gTRbeta was higher than that of gTRalphaA. However, gTRalphaB remained relatively constant. All three gTR mRNAs were detected in various tissues of adult fish, with considerable levels found in the pituitary and brain. The expression of gTRalphaA and gTRalphaB was ubiquitous, while the gTRbeta transcription in the pituitary was higher than other tissues. The results suggest that gTRs may be important in adult grouper brain function and that gTRalphaA and gTRalphaB may be important factors in metabolic regulation. In addition, gTRbeta may be the major TR isoform in the regulation of TSH activity by TH feedback in grouper. | 18,805,420 |
Single-molecule fluorescence resonance energy transfer assays reveal heterogeneous folding ensembles in a simple RNA stem-loop. | We have examined the folding ensembles present in solution for a series of RNA oligonucleotides that encompass the replicase translational operator stem-loop of the RNA bacteriophage MS2. Single-molecule (SM) fluorescence assays suggest that these RNAs exist in solution as ensembles of differentially base-paired/base-stacked states at equilibrium. There are two distinct ensembles for the wild-type sequence, implying the existence of a significant free energy barrier between "folded" and "unfolded" ensembles. Experiments with sequence variants are consistent with an unfolding mechanism in which interruptions to base-paired duplexes, in this example by the single-stranded loop and a single-base bulge in the base-paired stem, as well as the free ends, act as nucleation points for unfolding. The switch between folded and unfolded ensembles is consistent with a transition that occurs when all base-pairing and/or base-stacking interactions that would orientate the legs of the RNA stem are broken. Strikingly, a U-to-C replacement of a residue in the loop, which creates a high-affinity form of the operator for coat protein binding, results in dramatically different (un)folding behaviour, revealing distinct subpopulations that are either stabilised or destabilised with respect to the wild-type sequence. This result suggests additional reasons for selection against the C-variant stem-loop in vivo and provides an explanation for the increased affinity. | 18,805,425 |
Interplay between lipids and the proteinaceous membrane fusion machinery. | For membrane fusion to occur, opposed lipid bilayers initially establish a fusion pore, often followed by complete mixing of the fusing membranes. Contemporary views suggest that during fusion lipid bilayers are continuous passive platforms that are disrupted and remodeled by catalytic proteins. Some models propose that even the architecture and composition of the fusion pore might be dominated by proteins rather than lipids. Hence, lipids have no regulatory contribution to this process; they simply adapt their shape passively for filling space between otherwise autonomous protein machineries. However, an increasing number of experimental findings indicate that membrane fusion critically depends on a variety of lipids and lipid derivatives. Therefore, a purely proteocentric view describes fusion mechanisms insufficiently. Instead, lipids have functions probably at different levels, as (i) a general influence on the propensity of lipid bilayers to fuse, (ii) a role in recruiting exocytotic proteins to the plasma membrane, (iii) a role in organizing membrane domains for fusion and (iv) direct regulatory effects on fusion protein complexes. In this review we have made an attempt to bring together the large body of evidence supporting a major role for lipids in membrane fusion either directly or indirectly. | 18,805,437 |
A prime-boost vaccination protocol optimizes immune responses against the nucleocapsid protein of the SARS coronavirus. | Severe acute respiratory syndrome (SARS) is a serious infectious disease caused by the SARS coronavirus. We assessed the potential of prime-boost vaccination protocols based on the nucleocapsid (NC) protein co-administered with a derivative of the mucosal adjuvant MALP-2 or expressed by modified Vaccinia virus Ankara (MVA-NC) to stimulate humoral and cellular immune responses at systemic and mucosal levels. The obtained results demonstrated that strong immune responses can be elicited both at systemic and mucosal levels following a heterologous prime-boost vaccination protocol consisting in priming with NC protein add-mixed with MALP-2 by intranasal route and boosting with MVA-NC by intramuscular route. | 18,805,454 |
Immediate release pellets with lipid binders obtained by solvent-free cold extrusion. | Lipid-based drug delivery systems have spread in their use in pharmaceutical drug development. This work focuses on the use of lipid binders as alternative non-toxic extrusion aid for pellet formulations. The preparation of immediate release pellets with solid lipid binders through a solvent-free cold extrusion/spheronisation process was investigated in this study. Various binary, ternary and quaternary mixtures of powdered lipids and the model drug sodium benzoate were investigated and compared to well-known wet extrusion binders like microcrystalline cellulose and kappa-carrageenan. The cold lipid extrusion process offers multiple advantages as it is suitable for thermal sensitive as well as for hygroscopic drugs, furthermore no drying process to evaporate the solvent is needed and the process is feasible for different extruder types. Some of the developed pellets showed favourable properties like spherical shape, narrow size distribution, a high drug load of 80% sodium benzoate and a drug release of more than 90% within 40 min. The stability of drug release, which can be problematic when using lipid excipients, was sufficient for some mixtures, as storage under elevated temperatures changed the release profiles only slightly and no formulation released less than 80% within the first 60 min. A formulation with a mixture of hard fat, glycerol distearate and glycerol trimyristate showed the best results, as pellets with a low aspect ratio, narrow size distribution and complete drug release were obtained. Using appropriate mixtures of acylglycerides it becomes possible to produce pharmaceutical pellets with immediate release characteristics by cold extrusion and subsequent spheronisation. Thus, lipids are very promising alternatives to commonly used extrusion/spheronisation binders. | 18,805,483 |
Vasoprotective endothelial effects of a standardized grape product in humans. | The pathogenesis of coronary lesion development is a multi-factorial process involving a number of different cell types and covariates, and injury and dysfunction of the vascular endothelium is an important marker and likely participant in the initiation and/or progression of most forms of heart disease. In addition to chronic dysfunction of endothelial responses in patients with established heart disease, there is evidence that 'acute insults' can cause measurable dysfunction in vascular response in humans (drug toxicities, hypoxia, high fat meal). Such repeated acute insults may contribute to disease risk in otherwise healthy individuals or promote disease progression in established patients. Consumption of grape products, especially wine, has been linked to lower cardiovascular risk but the vascular endothelial effects of grape products in healthy normal subjects, in the absence of ethanol, have not been evaluated. We therefore tested the hypotheses that 1) a standardized product derived from fresh grapes (GP, acute and chronic consumption) improves endothelial performance in healthy normal young subjects, and 2) that concomitant grape consumption affects the 'acute endothelial insult' caused by a single standardized high fat meal (HF). Acute consumption of GP equivalent to 1.25 cups of fresh grapes caused significant improvement in brachial artery flow mediated dilation (FMD) within 3 h of consumption, when compared to control consumption of sugar solution (p<0.05). No acute changes in heart rate, hemodynamics, or lipid profiles were observed. When this 'dose' was then consumed twice daily for 3 weeks FMD was further improved and total antioxidant capacity in plasma was slightly increased (p<0.05), with no change in heart rate, hemodynamics, or lipid profiles. A single HF meal (900 cal, 49 g total fat) caused a 50% reduction in FMD response when consumed alone, and this effect coincided with increased blood triglyceride levels within 3 h post-consumption. In contrast the concomitant consumption of GP with the HF meal completely prevented this HF-induced vascular endothelial dysfunction (p<0.05), but had no effect on rising triglycerides. These data demonstrate that a modest intake of fresh grapes can have acute favorable effects on vascular endothelial function in normal healthy subjects, that chronic intake can further improve performance and concomitant intake can blunt the 'acute insult' to endothelium caused by a typical western HF meal. This effect is likely to be related to antioxidant effects at the endothelium, rather than changes in blood lipids. These data support epidemiological data of the health benefits of grapes, and demonstrate that 'favorable' food consumption can apparently reduce some toxicities induced by 'unfavorable' food consumption. | 18,805,507 |
Introducing N-glycans into natural products through a chemoenzymatic approach. | The present study describes an efficient chemoenzymatic method for introducing a core N-glycan of glycoprotein origin into various lipophilic natural products. It was found that the endo-beta-N-acetylglucosaminidase from Arthrobactor protophormiae (Endo-A) had broad substrate specificity and can accommodate a wide range of glucose (Glc)- or N-acetylglucosamine (GlcNAc)-containing natural products as acceptors for transglycosylation, when an N-glycan oxazoline was used as a donor substrate. Using lithocholic acid as a model compound, we have shown that introduction of an N-glycan could be achieved by a two-step approach: chemical glycosylation to introduce a monosaccharide (Glc or GlcNAc) as a handle, and then Endo-A catalyzed transglycosylation to accomplish the site-specific N-glycan attachment. For those natural products that already carry terminal Glc or GlcNAc residues, direct enzymatic transglycosylation using sugar oxazoline as the donor substrate was achievable to introduce an N-glycan. It was also demonstrated that simultaneous double glycosylation could be fulfilled when the natural product contains two Glc residues. This chemoenzymatic method is concise, site-specific, and highly convergent. Because N-glycans of glycoprotein origin can serve as ligands for diverse lectins and cell-surface receptors, introduction of a defined N-glycan into biologically significant natural products may bestow novel properties onto these natural products for drug discovery and development. | 18,805,520 |
Effect of LIMK2 RNAi on reorganization of the actin cytoskeleton in osteoblasts induced by fluid shear stress. | The biomechanical characteristics of bone tissue and its cells under mechanical stress are significant for bone biomechanics research, but the mechanism of mechanotransduction is still unknown. It has been established that the actin cytoskeleton of osteoblasts plays an important role in this process. However, the structure of the actin cytoskeleton is reorganized when loaded with mechanical stress, which results in changes in cell stiffness. These phenomena suggest that an actin-cytoskeleton-induced feedback regulation mechanism may be involved in the mechanotransduction of osteoblasts, but this has not yet been proven. The aim of this study was to explore the role of LIMK2 in the reorganization of the actin cytoskeleton induced by fluid shear stress in osteoblasts by using RNA interference. Balb/c mouse primary osteoblasts were divided into four groups. Cells in Groups 1 and 3 were transfected with negative control RNA, while cells in Groups 2 and 4 were transfected with a specific siRNA designed to silence the LIMK2 gene. Twenty-four hours after transfection, cells in Groups 1 and 2 were loaded with fluid shear stress at 12 dyne/cm2 while cells in Groups 3 and 4 were not. Compared with Group 1, the mean fluorescence density of the actin cytoskeleton in the other three groups was 28.9%, 45.7%, and 33.0%, respectively. These results indicate that LIMK2 plays an important role in the reorganization of the actin cytoskeleton induced by fluid shear stress. | 18,805,530 |
Assessment of in vivo and post-mortem mechanical behavior of brain tissue using magnetic resonance elastography. | The knowledge of in vivo brain tissue mechanical properties is essential in several biomedical engineering fields, such as injury biomechanics and neurosurgery simulation. Almost all existing available data have been obtained in vitro by invasive experimental protocols. However, the difference between in vivo and post-mortem mechanical properties remains poorly known, essentially due to the lack of a common method that could measure them both in vivo and ex vivo. In this study, we report the use of magnetic resonance elastography (MRE) for the non-invasive assessment of in vivo brain tissue viscoelastic properties and for the investigation of their evolution after the death. Experiments were performed on seven adult male rats. Shear storage and loss moduli were measured in vivo, just after death and at post-mortem time of approximately 24h. A significant increase in shear storage modulus G(') of approximately 100% was found to occur just after death (p=0.002), whereas no significant difference was found between in vivoG(') and G(') at 24h post-mortem time. No significant difference was found between shear loss modulus G('')in vivo and just after death, whereas a decrease of about 50% was found to occur after 24h (p=0.02). These results illustrate the ability of MRE to investigate some of the critical soft tissue biomechanics-related issues, as it can be used as a non-invasive tool for measuring soft tissue viscoelastic properties. | 18,805,534 |
Autoimmune-mediated oxidative stress and endothelial dysfunction: implications of accelerated vascular injury in type I diabetes. | The pathogenesis of cardiovascular disease in the setting of type 1 diabetes is not well-defined. The hypothesis that hyperglycemia is largely responsible for vascular endothelial dysfunction, and ultimately atherosclerosis, continues to evolve. However, despite tight glucose control, a subset of patients still develop clinically significant occlusive disease. While the specific mechanisms of persistent vascular injury are not clear, an increasing body of evidence suggests a dysregulated autoimmune response may contribute to the development of vascular injury. That is, the same inflammatory response that is responsible for pancreatic beta-cell destruction may facilitate chronic vascular endothelial injury prior to the onset of hyperglycemia. Herein, we discuss (1) the clinical experience with tight glycemic control and the risk of cardiovascular disease in patients with type 1 diabetes; (2) the cellular mechanisms involved in vascular endothelial injury; and (3) the long-term clinical implications of autoimmune-mediated vascular disease and current treatment strategies. | 18,805,553 |
Mechanism of injury predicts patient mortality and impairment after blunt trauma. | Different mechanisms of injury (MOI), such as motor vehicle crashes, falls, or pedestrians struck by motor vehicle impart varying degrees of force and energy transfer that may impact outcomes. This study analyzed the independent relationship between MOI and mortality and functional outcomes following blunt trauma among adults. Retrospective review of blunt trauma patients 15 y and older in the National Trauma Data Bank from 2001 to 2005. Primary outcome measures were mortality and presence of functional deficit in speech, walking, or feeding at discharge. MOI categories, identified by ICD-9 E codes, were motor vehicle crash, pedestrian struck by motor vehicle, motorcycle crash, falls at same level and from any height, and bicycle crash. A multiple regression analysis was performed adjusting for patient demographics and injury severity variables with motor vehicle crash as the reference mechanism group. Over the period studied, 515,464 patients met inclusion criteria. Mean Injury Severity Score (16.9), mortality rate (11%), and extremity injury (20%) were highest among pedestrians struck by motor vehicle, and head injury (16%) highest for motorcyclists. Overall, 52% had impaired ambulation, 16% impaired feeding, and 10% impaired speech. Adjusted odds of death, impaired walking, and impaired speaking were highest for pedestrians struck by motor vehicle, and impaired feeding highest for motorcyclists. After adjusting for confounders, MOI was found to independently predict mortality and functional impairment at hospital discharge. Current injury assessment models could be greatly enhanced by including MOI, and we propose routine adjustment for injury mechanism in trauma outcomes research. | 18,805,554 |
Is meltwater from Alpine glaciers a secondary DDT source for lakes? | A sharp increase in 2005 of pp'DDT and its metabolites was observed in mussels and fish from lakes Como and Iseo, the main glacier-fed southern Alpine lakes. DDTs in zebra mussels (Dreissena polymorpha) were more than 150 times higher than levels in 2003, and concentrations in pelagic fish (0.12 mgkg(-1) w.w.) exceeded the Italian safety threshold for human consumption (0.05 mgkg(-1) w.w.). The histological examination of the ovaries revealed many mussels with oocyte degeneration throughout the studied period. Prior to being banned in Italy in 1978, DDT was used in large amounts for fruit-tree treatment from the 1950s to 1970s in valleys just below the glaciers. Since glacier volume was increasing at that time and then continuously retreated, meltwater should be the main cause of the pollution peak recently observed in biota of downstream lakes. PCBs did not peak in biota tissues to a comparable extent probably because local sources were not as important as for DDTs. | 18,805,565 |
Effects of long-term soil amendment with sewage sludges on soil humic acid thermal and molecular properties. | Sewage sludges are frequently used as soil amendments due to their high contents of organic matter and nutrients, particularly N and P. However, their effects upon the chemistry of soil humic acids, one of the main components of the soil organic matter, need to be more deeply studied in order to understand the relation between organic matter structure and beneficial soil properties. Two sewage sludges subjected to different types of pre-treatment (composted and thermally dried) with very different chemical compositions were applied for three consecutive years to an agricultural soil under long-term field study. Thermal analysis (TG-DTG-DTA) and solid-state (13)C NMR spectroscopy were used to compare molecular and structural properties of humic acids isolated from sewage sludges, and to determine changes in amended soils. Thermally dried sewage sludge humic acids showed an important presence of alkyl and O/N-alkyl compounds (70%) while composted sludge humic acids comprised 50% aromatic and carbonyl carbon. In spite of important differences in the initial chemical and thermal properties of the two types of sewage sludges, the chemical and thermal properties of the soil humic acids were quite similar to one another after 3 years of amendment. Long-term application of both sewage sludges resulted in 80-90% enrichment in alkyl carbon and organic nitrogen contents of the soil humic acid fraction. | 18,805,567 |
Short- and medium-term effects of fire and fire-fighting chemicals on soil micronutrient availability. | The impact of fire and three fire-fighting chemicals (FFC) on soil micronutrient availability was evaluated 1, 90 and 365 days after a prescribed fire. Five treatments were considered: unburnt soil (US) and burnt soil with 2 l m(-2) of water (BS) or water with foaming agent Auxquímica RFC-88 at 1% (BS+Fo), Firesorb at 1.5% (BS+Fi) and FR-Cross ammonium polyphosphate at 20% (BS+Ap). Pre-fire contents of available micronutrient were homogeneous among plots and high (Fe, Zn) or insufficient (Co, Cu, Mn) for plant nutrition. At t=1 day, Fe availability decreased greatly in burnt treatments, with significant differences in BS+Fi (-50%) and BS+Ap (-75%), contrasting with Fe richness of the ammonium polyphosphate. The fire induced a significant increase (9-16x) of available Mn in burnt treatments that lasted for at least three months; the FFC effect on soil available Mn was imperceptible, despite the noticeable amounts of Mn they supplied (especially Firesorb and ammonium polyphosphate). In burnt soils, the Fe/Mn ratio also decreased strongly (92-99%) and significantly till t=90 days. A high increase was also found, at t=1 day, for the available Zn in all burnt treatments and, although the ammonium polyphosphate provided more Zn than the Firesorb, the increment was only significant in BS+Fi plots (+100%). Neither fire nor FFC effects on soil Cu availability were found. The slight increase of Co availability in BS, BS+Fo and BS+Ap at t=1 day was followed by a transient decrease in all burnt treatments at t=90 days. Except the Mn and the Fe/Mn ratio in BS+Ap, which remained significantly higher and lower, respectively, the indices of available micronutrients at t=365 days in all burnt soils were similar to the pre-fire levels. | 18,805,571 |
Robotic-assisted laparoscopic approach for posterior bladder neck dissection and placement of pediatric bladder neck sling: initial experience. | Bladder neck sling cystourethropexy is a common procedure used to correct intrinsic sphincter deficiency in children with spinal dyspharism. Various modifications of the procedure have been made but all involve circumferential dissection of the bladder neck and proximal urethra. The posterior dissection can be challenging and can result in injury to the rectum, urethra, or vagina. The posterior approach to the bladder neck as reported by Lottmann and later by de Badiola addresses these potential complications. Using these principles of the posterior approach, we performed a robotic-assisted laparoscopic placement of an acellular human dermal allograft bladder neck sling in 2 patients. We present our initial experience regarding this surgical technique. The diagnosis of intrinsic sphincter deficiency was established in 2 female patients, aged 9 and 10 years. Both patients had a neurogenic bladder secondary to spina bifida. Video urodynamics confirmed adequate bladder compliance and intrinsic sphincter deficiency. Robotic-assisted laparoscopic placement of a bladder neck sling was performed in both patients. Both procedures were completed intracorporeally. The mean blood loss was 20 mL. The mean operative time was 189 minutes. No intraoperative or postoperative complications occurred. The mean hospital stay was 3 days (range 2-4). The follow-up ranged from 13 to 22 months. Postoperative studies revealed continued low-pressure, compliant bladders and stable upper tracts. At last follow-up, the 2 patients were using catheterization without difficulty and were continent. The robotic-assisted laparoscopic approach to performing bladder neck dissection and placement of a bladder neck sling in children is technically feasible. | 18,805,574 |
Synchronous occult cancers of the endometrium and fallopian tube in an MSH2 mutation carrier at time of prophylactic surgery. | Women with Lynch syndrome have a 40 to 60% lifetime risk of endometrial cancer and a 10 to 12% lifetime risk of ovarian cancer and may consider prophylactic gynecological surgery as an option for risk reduction. We report a case of synchronous primary cancers of the endometrium and fallopian tube diagnosed at time of prophylactic surgery in an MSH2 mutation carrier. Risk-reducing gynecological surgery in Lynch syndrome must include complete removal of the fallopian tubes in addition to the ovaries and endometrium, followed by careful pathological review. Prospective studies are needed to clarify the incidence of occult primary carcinoma of the fallopian tube among female MMR mutation carriers undergoing prophylactic surgery. | 18,805,575 |
Maternal and fetal C-reactive protein genotype and first trimester CRP concentrations in maternal plasma. | Maternal plasma CRP concentrations in pregnancy are increased over pre-pregnancy values and high concentrations have been associated with adverse obstetrical outcomes. The objective of this study was to explore the relationship between maternal and fetal variation in C-reactive protein (CRP) genotype and maternal plasma CRP concentrations in the first trimester in low risk patients. DNA was extracted from maternal and cord blood of subjects in a prospective observational cohort. Single-nucleotide polymorphism (SNP) selection was made using a linkage disequilibrium bin approach. CRP concentrations were measured in first trimester maternal plasma using an enzyme-linked immunosorbent assay (ELISA) kit. Kruskal-Wallis rank testing was used to analyze genetic and clinical determinants of CRP concentrations. Genotype results were available in 190 mother-baby pairs. There was no significant difference in CRP concentration among maternal or fetal CRP genotypes. Thus, first trimester concentrations of maternal plasma CRP in low risk subjects do not appear to be significantly associated with CRP genotype. Instead, differences in clinical factors probably have more influence on baseline maternal CRP concentrations. | 18,805,592 |
Cardiovascular risk and memory in non-demented elderly women. | To determine whether cardiovascular (CV) risk is associated with subtle memory deficits in non-demented, healthy older women with a family history of Alzheimer disease (AD). Baseline data of 375 participants from a randomized, double-blind placebo-controlled primary prevention trial to test the efficacy of hormone replacement therapy in delaying AD and cognitive decline were analyzed. All subjects were women over 65 with a family history of AD who had normal cognition and no active heart disease at baseline. A baseline memory composite score was calculated, consisting of immediate and delayed recall of verbal and nonverbal material. Multiple linear regression was performed to examine the association of relative CV risk with memory functioning; age, ethnicity and education level were included as covariates. Mean baseline memory composite score was significantly higher in those with low relative CHD risk than those with high relative CHD risk. These findings suggest that subtle elevation of CHD risk may negatively affect memory functioning even in otherwise healthy, non-demented older women without a history of heart disease. | 18,805,604 |
Acquired Gitelman syndrome in a patient with primary Sjögren syndrome. | Acquired Gitelman syndrome (GS) associated with Sjögren syndrome (SS) is rare, and the test to determine the pathophysiological state of acquired GS in patients with primary SS has not been reported previously. A 47-year-old woman with sicca complex presented to our clinic with intermittent muscle cramping and weakness involving both lower extremities over several months. Laboratory findings showed hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria, which met the criteria for GS. Diagnostic evaluation identified primary SS as the cause of the acquired GS. Light microscopic examination of renal tissue from the patient showed mild tubulointerstitial nephritis. Immunohistochemical staining of renal tissue showed the absence of the sodium-chloride cotransporter (NCCT) in the distal convoluted tubules. Incubation of the patient's serum with normal mouse kidney tissue showed a pattern of NCCT in the distal convoluted tubules similar to that of incubation of normal mouse kidney with the rabbit polyclonal anti-NCCT antibody. This is a rare case of acquired GS associated with primary SS, and our findings suggest the presence of circulating autoantibodies to NCCT. | 18,805,608 |
Caspase inhibitor zVAD.fmk reduces infarct size after myocardial ischaemia and reperfusion in rats but not in mice. | Apoptosis of cardiomyocytes has been suggested to contribute to outcome following myocardial ischaemia and reperfusion (MI/R). Caspase inhibitors were developed as potential therapeutics for MI/R. However, various reports using the broad-spectrum caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) in the latter setting present conflicting results. Therefore, it is still unclear whether inhibition of apoptosis by caspase inhibitors promotes cardioprotection. This study evaluated whether zVAD.fmk or novel caspase inhibitor quinoline-Val-Asp(Ome)-CH2-O-phenoxy (Q-VD-OPh) reduce myocardial infarct size in mice. Secondly, we tested zVAD.fmk's potential infarct-sparing effects in rats and whether these are accompanied by improved left ventricular function. In mice neither zVAD.fmk nor Q-VD-OPh reduced infarct size. In rats, however, zVAD.fmk reduced infarct size following ischaemia (25min) and reperfusion (7 days) by approximately 53%. This was, however, accompanied by an increase in left ventricular end-diastolic pressure. This study provides further evidence that abrogation of apoptosis via caspase inhibition might not be sufficient to effectively limit infarct size following MI/R. | 18,805,622 |
Toxic waste in our midst: towards an interdisciplinary analysis. | Intractable industrial legacies present new challenges to governance. Amongst the persistent organic pollutants, now managed internationally under the Stockholm Convention, hexachlorobenzene (HCB) stands out in all three classes of chemicals (pesticides, industrial chemicals and unintended by-products). This paper introduces twelve interdisciplinary papers contributing to our understanding of decision-making processes using a case study of HCB and industry-community relations in Sydney's industrial heartland. In this collection, authors align new political theory and emerging management theory, and they analyse the case study from several disciplines. Disputes such as that over HCB destablilise the political/administrative/technoscientific regime that is the modern state. Citizens engage in 'sub-political' processes which require recognition of what Ulrich Beck and others have termed 'individualisation'. This sees decision-forming and decision-making functions push outwards into community-driven structures. There we find new styles of public participation, resolution of asymmetries between knowledge and expertise, and new corporate behaviour. | 18,805,624 |
Nitrate removal from electro-oxidized landfill leachate by ion exchange. | Treatment of landfill leachates by electrochemical oxidation led to the complete removal of chemical oxygen demand and ammonium nitrogen. However, as result of the ammonium oxidation, the partial formation of nitrate ions was observed. Ion exchange technology was investigated as a polishing step in the treatment of landfill leachates. Removal of nitrate from aqueous solutions was studied using two selective anion exchangers: Purolite A 520E and Purolite A 300, under a fixed bed configuration. The following aspects of the ion exchange system were experimentally analyzed: (i) the influence of the presence of other competitive anions in solution, sulfate and chloride, during the loading step, (ii) the breakthrough point and resin saturation as a function of chloride concentration in the feed stream and, (iii) the efficiency of the regeneration step working with NaCl solutions at several concentrations. After a comparison of the experimental results, it was concluded that the resin Purolite A 300 showed a better behavior. Experimental analysis of the equilibrium isotherms made it possible to determine the equilibrium constant (K=3.21) and the maximum capacity (q(max)=183mgg(-1)), important parameters in the design of the treatment process. | 18,805,640 |
Incidence and determinants of initiation into cocaine injection and correlates of frequent cocaine injectors. | To investigate the incidence and correlates of cocaine injection initiation and the impacts of daily cocaine injection among a cohort of injection drug users. Among 1603 participants, from May 1996 to December 2005, risk factors for initiation of cocaine injection among baseline heroin users were determined by Cox proportional hazards regression and correlates of daily cocaine injection by generalized estimating equations. Of the 238 individuals who had never injected cocaine, 200 (84%) had at least one follow-up visit and 121 (61%) consequently initiated into cocaine injection, yielding an incidence density of initiation into cocaine injection of 21.9% (95% confidence interval (CI): 17.9-25.8) per 100 person-years. In a multivariate model, Downtown Eastside (DTES) residence (adjusted hazard ratio (AHR)=2.46, 95% CI: 1.68-3.60), incarceration (AHR=1.50, 95% CI: 1.01-2.24), requiring help injecting (AHR=1.57, 95% CI: 0.99-2.49), and binge drug use (AHR=1.82, 95% CI: 1.22-2.73) remained associated with initiation into cocaine injection. DTES residence (adjusted odds ratio (AOR)=1.99, 95% CI: 1.62-2.46), unstable housing (AOR=1.28, 95% CI: 1.04-1.53), incarceration (AOR=1.29, 95% CI: 1.04-1.60), sex trade involvement (AOR=1.46, 95% CI: 1.15-1.85), requiring help injecting (AOR=2.11, 95% CI: 1.73-2.58)), borrowing syringes (AOR=1.81, 95% CI: 1.35-2.43) and binge drug use (AOR=2.16, 95% CI: 1.81-2.58) were independently associated with daily cocaine injection. The baseline prevalence and subsequent incidence of initiation into cocaine injection was high. Daily cocaine injection was independently associated with a number of health and social harms, including elevated HIV risk behavior. | 18,805,655 |
Predictors of outcome for short-term medically supervised opioid withdrawal during a randomized, multicenter trial of buprenorphine-naloxone and clonidine in the NIDA clinical trials network drug and alcohol dependence. | Few studies in community settings have evaluated predictors, mediators, and moderators of treatment success for medically supervised opioid withdrawal treatment. This report presents new findings about these factors from a study of 344 opioid-dependent men and women prospectively randomized to either buprenorphine-naloxone or clonidine in an open-label 13-day medically supervised withdrawal study. Subjects were either inpatient or outpatient in community treatment settings; however not randomized by treatment setting. Medication type (buprenorphine-naloxone versus clonidine) was the single best predictor of treatment retention and treatment success, regardless of treatment setting. Compared to the outpatient setting, the inpatient setting was associated with higher abstinence rates but similar retention rates when adjusting for medication type. Early opioid withdrawal severity mediated the relationship between medication type and treatment outcome with buprenorphine-naloxone being superior to clonidine at relieving early withdrawal symptoms. Inpatient subjects on clonidine with lower withdrawal scores at baseline did better than those with higher withdrawal scores; inpatient subjects receiving buprenorphine-naloxone did better with higher withdrawal scores at baseline than those with lower withdrawal scores. No relationship was found between treatment outcome and age, gender, race, education, employment, marital status, legal problems, baseline depression, or length/severity of drug use. Tobacco use was associated with worse opioid treatment outcomes. Severe baseline anxiety symptoms doubled treatment success. Medication type (buprenorphine-naloxone) was the most important predictor of positive outcome; however the paper also considers other clinical and policy implications of other results, including that inpatient setting predicted better outcomes and moderated medication outcomes. | 18,805,656 |
Measurement of the intrarenal arterial resistance index for the identification and prediction of diabetic nephropathy. | High intrarenal resistance index (RI) predicts renal function in several conditions; its use in the prediction of diabetic nephropathy (DN) is little explored. We aimed (1) to compare RI in diabetic and non diabetic hypertensive patients, and (2) to evaluate whether high RI is associated with clinical signs of DN and its progression over time. observational, prospective. 92 type 2 diabetic patients and 37 non-diabetic controls aged 40-70, with hypertension and normal renal function. We measured ultrasound RI and, among others, creatinine, estimated glomerular filtration rate and urinary albumin excretion rate (AER) at baseline and after 4.5 years follow-up. Progression of albuminuric state (i.e., transition from baseline normo-microalbuminuria to follow-up micro-macroalbuminuria) was evaluated. RI was significantly higher in diabetic than non-diabetic participants (0.69+/-0.05 vs 0.59+/-0.05, p<0.001). Diabetic patients with RI>or=0.73, i.e., above the 80th percentile of the RI distribution, had significantly higher baseline AER and a more frequent progression of the albuminuric state compared to patients with RI<0.73 (27.7microg/mg [12.1-235.4] vs 15.1microg/mg [8.6-33.4]; 52.9% vs 9.5%, respectively). AER increased significantly from baseline to follow-up in patients with RI>or=0.73 (from 27.7microg/mg [12.1-235.4] to 265.0microg/mg [23.8-1018.1], p<0.01), but not in those with RI<0.73 (from 15.1microg/mg [8.6-33.4] to 16.1microg/mg [10.7-67.2], ns). OR for progression of albuminuric state, adjusted for established predictors of DN, including baseline AER, was 5.01 (1.4-17.7, 95% CI) for patients with RI>or=0.73 vs <0.73. Findings were confirmed in patients with normoalbuminuria at baseline. In diabetic patients, high RI (>or=0.73) is associated with features of DN and its progression over time, independent of albuminuria. | 18,805,683 |
Why don't out-of-treatment individuals enter methadone treatment programmes? | Despite the proven effectiveness of methadone treatment, the majority of heroin-dependent individuals are out-of-treatment. Twenty-six opioid-dependent adults who met the criteria for methadone maintenance who were neither seeking methadone treatment at the time of study enrollment, nor had participated in such treatment during the past 12 months, were recruited from the streets of Baltimore, Maryland through targeted sampling. Ethnographic interviews were conducted to ascertain participants' attitudes toward methadone treatment and their reasons for not seeking treatment. Barriers to treatment entry included: waiting lists, lack of money or health insurance, and requirements to possess a photo identification card. For some participants, beliefs about methadone such as real or rumored side effects, fear of withdrawal from methadone during an incarceration, or disinterest in adhering to the structure of treatment programmes kept them from applying. In addition, other participants were not willing to commit to indefinite "maintenance" but would have accepted shorter time-limited methadone treatment. Barriers to treatment entry could be overcome by an infusion of public financial support to expand treatment access, which would reduce or eliminate waiting lists, waive treatment-related fees, and/or provide health insurance coverage for treatment. Treatment programmes could overcome some of the barriers by waiving their photo I.D. requirements, permitting time-limited treatment with the option to extend such treatment upon request, and working with corrections agencies to ensure continued methadone treatment upon incarceration. | 18,805,686 |
Spectroscopic and theoretical study of 2-acetylphenyl-2-naphthoate. | Mid-, far-infrared and Raman vibrational spectra of 2-acetylphenyl-2-naphthoate have been measured at room and low temperatures. The molecule was also analyzed by means of ab initio calculations. The conformational space has been scanned using molecular dynamics and complemented with functional density calculations that optimize the geometry of the lowest energy conformers 2-acetylphenyl-2-naphthoate as obtained in the simulations. The vibrational frequencies and the (1)H and (13)C NMR chemical shifts were assigned using functional density calculations. The theoretical chemical shift values were compared with the experimental ones. The molecular electrostatic potential maps were obtained and analyzed. | 18,805,730 |
[Some recent ethical dilemmas in randomized controlled clinical trials]. | Randomized controlled clinical trials (RCTs) are the golden standard of contemporary medical research. Just because they are ever more widespread, they stand at the focus of intense ethical debate. The debates have focused on the questions, how much the research participants can benefit from the research, and even if they can benefit from it, can a research ever be called therapeutic? Is not the notion of therapeutic research a misconception? Furthermore it has been debated when it is ethically acceptable to start an RCT, and is it acceptable to randomly assign research participants? When is it acceptable to use a placebo controlled trial? It has been debated, how to interpret the conception of "best... method" in the Declaration of Helsinki 2000. The article makes an attempt to survey some of the lessons of these debates. | 18,805,759 |
[Clinical application of nanoparticles, and their possible health risk]. | Nanomaterials are getting rapidly developing practical applications, beside many others also in the clinical practice. Their beneficial attributes make the use of the nanostructures a large improvement in effective therapy as coating of implants, bone replacement materials, coating of active substances, nano-sized liposomes to achieve better pharmacologic qualities. Beside new beneficial chemical qualities originating from their size, due to the use of nanomaterials also adverse health effects may occur. Only in view of the possible effects on human health is the responsible use acceptable. The difference in qualities from other kinds of material can be explained by the nano-size. Investigations performed in the last decade have shown beside their local effect also systemic effects, like the rise of reactive oxygen species production, increase of platelet aggregation, which raises the cardiovascular risk. Due to the incomplete knowledge available now, it is not possible to assess the exact health risk; accordingly the application of nanomaterials in medical care has to be especially careful because of their possible partly unknown adverse health effects. | 18,805,764 |
Human T-cell leukemia virus type 1 HBZ protein bypasses the targeting function of ubiquitination. | Human T-cell leukemia virus type 1 (HTLV-1) encodes an antisense viral gene product termed HTLV-1 basic leucine-zipper factor (HBZ). HBZ forms heterodimers with c-Jun, a member of the AP-1 family, and promotes its proteasomal degradation. Although most proteasomal substrates are targeted for degradation via conjugation of polyubiquitin chains, we show that ubiquitination is not required for HBZ-mediated proteasomal degradation of c-Jun. We demonstrate that HBZ directly interacts with both the 26 S proteasome and c-Jun and facilitates the delivery of c-Jun to the proteasome without ubiquitination. HBZ acts as a tethering factor between the 26 S proteasome and its substrate, thereby bypassing the targeting function of ubiquitination. These findings disclose a novel viral strategy to utilize the cellular proteolytic system for viral propagation. | 18,805,793 |
Cellular mechanisms of Cnidarian bleaching: stress causes the collapse of symbiosis. | Cnidarian bleaching is a breakdown in the mutualistic symbiosis between host Cnidarians, such as reef building corals, and their unicellular photosynthetic dinoflagellate symbionts. Bleaching is caused by a variety of environmental stressors, most notably elevated temperatures associated with global climate change in conjunction with high solar radiation, and it is a major contributor to coral death and reef degradation. This review examines the underlying cellular events that lead to symbiosis dysfunction and cause bleaching, emphasizing that, to date, we have only some pieces of a complex cellular jigsaw puzzle. Reactive oxygen species (ROS), generated by damage to both photosynthetic and mitochondrial membranes, is shown to play a central role in both injury to the partners and to inter-partner communication of a stress response. Evidence is presented that suggests that bleaching is a host innate immune response to a compromised symbiont, much like innate immune responses in other host-microbe interactions. Finally, the elimination or exit of the symbiont from host tissues is described through a variety of mechanisms including exocytosis, host cell detachment and host cell apoptosis. | 18,805,804 |
Effects of [Ca2+]i and pH on epithelial Na+ channel activity of cultured mouse cortical collecting ducts. | [Ca2+]i and pH have been demonstrated to affect Na+ transport in epithelium mediated via the apical epithelial Na+ channel (ENaC). However, it still remains unclear whether the effects of [Ca2+]i and intracellular pH (pHi) on ENaC activity are direct. In this study, inside-out recording was employed to clarify the effects of pH(i) and [Ca2+]i on ENaC activity. We found that elevation of [Ca2+]i induced a significant inhibition of ENaC open probability without altering channel conductance. The inhibitory effect was due to a direct interaction between Ca2+ and ENaC, and is dependent on [Ca2+]i. pHi also directly regulated ENaC open probability. Lower pHi (<7.0) reduced the ENaC open probability as shown in shorter opening time, and higher pH(i) (>7.0) enhanced the ENaC open probability as shown in augmented opening time. pHi did not cause any alteration in channel conductance. The effects of pHi on ENaC open probability could be summarized as an S-shaped curve around pH 7.2. | 18,805,816 |
Investigating the variations in survival rates for very preterm infants in 10 European regions: the MOSAIC birth cohort. | To investigate the variation in the survival rate and the mortality rates for very preterm infants across Europe. A prospective birth cohort of very preterm infants for 10 geographically defined European regions during 2003, followed to discharge home from hospital. All deliveries from 22 + 0 to 31 + 6 weeks' gestation. All outcomes of pregnancy by gestational age group, including termination of pregnancy for congenital anomalies and other reasons, antepartum stillbirth, intrapartum stillbirth, labour ward death, death after admission to a neonatal intensive care unit (NICU) and survival to discharge. Overall the proportion of this very preterm cohort who survived to discharge from neonatal care was 89.5%, varying from 93.2% to 74.8% across the regions. Less than 2% of infants <24 weeks' gestation and approximately half of the infants from 24 to 27 weeks' gestation survived to discharge home from the NICU. However large variations were seen in the timing of the deaths by region. Among all fetuses alive at onset of labour of 24-27 weeks' gestation, between 84.0% and 98.9% were born alive and between 64.6% and 97.8% were admitted to the NICU. For babies <24 weeks' gestation, between 0% and 79.6% of babies alive at onset of labour were admitted to neonatal intensive care. There are wide variations in the survival rates to discharge from neonatal intensive care for very preterm deliveries and in the timing of death across the MOSAIC regions. In order to directly compare international statistics for mortality in very preterm infants, data collection needs to be standardised. We believe that the standard point of comparison should be using all those infants alive at the onset of labour as the denominator for comparisons of mortality rates for very preterm infants analysing the cohort by gestational age band. | 18,805,823 |
Diagnostic evaluation of people with hypertension in low income country: cohort study of "essential" method of risk stratification. | To explore the predictive power of a risk stratification method for people with hypertension based on "essential" procedures (that is, available in economically less developed areas of the world), comparing it in the same population with the results given by the method suggested by the 1999 World Health Organization-International Society of Hypertension (WHO-ISH) guidelines. Prospective cohort study of outcomes according to cardiovascular risk profile at baseline. Primary care in a poor rural area of the Ecuadorian forest. 504 people with hypertension prospectively monitored for a mean of 6.7 (SD 2.3) years. Essential data included blood pressure, medical history, smoking, age, sex, and diagnosis of diabetes; the WHO-ISH methods additionally included measurement of fasting blood glucose, total cholesterol, and creatinine, urinalysis, and electrocardiography. Cardiovascular events and total deaths. With both methods there was a highly significant association between the level of predicted risk and the incidence of cardiovascular events and of total deaths: up to three quarters of all cardiovascular events and two thirds of all deaths were reported among people classified as at high or very high risk with either method. The predictive discrimination of the essential method is comparable with the WHO-ISH with C statistics (95% confidence interval) of 0.788 (0.721 to 0.855) and 0.744 (0.673 to 0.815), respectively, for cardiovascular events and 0.747 (0.678 to 0.816) and 0.705 (0.632 to 0.778) for total mortality. The risk stratification of patients with hypertension with an essential package of variables (that is, available and practicable even in the economically less developed areas of the world) serves at least as well as the more comprehensive method proposed by WHO-ISH. | 18,805,835 |
Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. | During the last 15 years, high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) has globally been performed for severe multiple sclerosis (MS). Most patients have been in progressive phase with long disease duration. As a rule, treatment effect has been minor or moderate. Since 2004, we have performed HSCT in nine young patients with "malignant" relapsing-remitting MS. Criteria for treatment were short duration of disease; very frequent, severe relapses; recent improvement periods indicating potential for recovery after strong immunosuppression. Median age at treatment was 27 (range 9-34) years, MS duration 26 (4-100) months, and annualized relapse rate 10 (4-12). Median Disability Status Scale (extended disability status scale, EDSS) at HSCT was 7.0 (3.5-8.0). Median follow-up time April 2008 is 29 (23-47) months. Median EDSS improvement is 3.5 (1.0-7.0), clearly surpassing most previous reports. One patient relapsed mildly with rapid recovery 7 months after HSCT. All patients are otherwise stable, median EDSS being 2.0 (0-6.0). Before HSCT, 61 relapses occurred in 82 patient months; during follow-up, one relapse in 289 patient months. This small series of patients with "malignant" relapsing-remitting MS suggests HSCT to be an effective treatment option for this relatively rare disease course. It further suggests that future criteria for HSCT in MS should be close to the present ones. | 18,805,841 |
Rigid spin-labeled nucleoside C: a nonperturbing EPR probe of nucleic acid conformation. | Rigid spin-labeled nucleoside C, an analog of deoxycytidine that base-pairs with deoxyguanosine, was incorporated into DNA oligomers by chemical synthesis. Thermal denaturation experiments and circular dichroism (CD) measurements showed that C has a negligible effect on DNA duplex stability and conformation. Nucleoside C was incorporated into several positions within single-stranded DNA oligomers that can adopt two hairpin conformations of similar energy, each of which contains a four-base loop. The relative mobility of nucleotides in the alternating C/G hairpin loops, 5'-d(GCGC) and 5'-d(CGCG), was determined by electron paramagnetic resonance (EPR) spectroscopy. The most mobile nucleotide in the loop is the second one from the 5'-end, followed by the third, first and fourth nucleotides, consistent with previous NMR studies of DNA hairpin loops of different sequences. The EPR hairpin data were also corroborated by fluorescence spectroscopy using oligomers containing reduced C (C(f)), which is fluorescent. Furthermore, EPR spectra of duplex DNAs that contained C at the end of the helix showed features that indicated dipolar coupling between two spins. These data are consistent with end-to-end duplex stacking in solution, which was only observed when G was paired to C, but not when C was paired with A, C or T. | 18,805,908 |
Gender dimorphism in body composition abnormalities in acromegaly: males are more affected than females. | Acromegaly changes body composition (BC), but long-term gender differences have not been reported. To evaluate BC in active and controlled acromegalic patients. Clinical and biochemical variables and BC (by dual-energy X-ray absorptiometry) were evaluated in 60 acromegalic patients (19 active, 41 controlled) and 105 controls, matched for age and gender. Acromegalic males (n=24) had more total mass (89+/-13 vs 76.5+/-15.3 kg, P<0.001), lean body mass (LBM; 64.6+/-8.7 vs 56.4+/-5.8 kg, P<0.001), and bone mineral content (BMC; 2.9+/-0.5 vs 2.6+/-0.3 kg, P<0.05) than controls (n=33). Controlled male patients (n=14) had more total mass (89+/-14.7 vs 76.5+/-15.3 kg, P<0.05) and a trend to have more LBM (61.8+/-9.4 vs 56.4+/-5.8 kg, P=0.065) than controls. Only in active disease was a decrease in fat mass (FM) observed, compared with controlled patients and controls (males: 19.5+/-5.3 vs 27+/-6.2 and 25.9+/-4%, P<0.001; females: 30.3+/-6.7 vs 37.1+/-5.8 and 36.5+/-6.6%, P<0.01). In females, no further differences were observed. No differences in BMC were found between eugonadal and hypogonadal acromegalic patients, but in hypogonadal females, acromegaly appeared to prevent the BMC loss seen in hypogonadal postmenopausal controls. GH and IGF1 levels were negatively correlated with FM (males, P<0.05; females, P<0.001), but in the regression analysis GH was a predictor of FM only in women. Control of acromegaly reverts decreased FM in both genders; only in males more total mass and a trend for more LBM persist. The anabolic effect of GH on bone reverted in cured males, but persisted in females and appeared to override the bone loss of menopause. | 18,805,912 |
The Gaussian curvature elastic energy of intermediates in membrane fusion. | The Gaussian curvature elastic energy contribution to the energy of membrane fusion intermediates has usually been neglected because the Gaussian curvature elastic modulus, kappa, was unknown. It is now possible to measure kappa for phospholipids that form bicontinuous inverted cubic (Q(II)) phases. Here, it is shown that one can estimate kappa for lipids that do not form Q(II) phases by studying the phase behavior of lipid mixtures. The method is used to estimate kappa for several lipid compositions in excess water. The values of kappa are used to compute the curvature elastic energies of stalks and catenoidal fusion pores according to recent models. The Gaussian curvature elastic contribution is positive and similar in magnitude to the bending energy contribution: it increases the total curvature energy of all the fusion intermediates by 100 units of k(B)T or more. It is important to note that this contribution makes the predicted intermediate energies compatible with observed lipid phase behavior in excess water. An order-of-magnitude fusion rate equation is used to estimate whether the predicted stalk energies are consistent with the observed rates of stalk-mediated processes in pure lipid systems. The current theory predicts a stalk energy that is slightly too large, by approximately 30 k(B)T, to rationalize the observed rates of stalk-mediated processes in phosphatidylethanolamine or N-monomethylated dioleoylphosphatidylethanolamine systems. Despite this discrepancy, the results show that models of fusion intermediate energy are accurate enough to make semiquantitative predictions about how proteins mediate biomembrane fusion. The same rate model shows that for proteins to drive biomembrane fusion at observed rates, they have to perform mediating functions corresponding to a reduction in the energy of a purely lipidic stalk by several tens of k(B)T. By binding particular peptide sequences to the monolayer surface, proteins could lower fusion intermediate energies by altering the elastic constants of the patches of lipid monolayer that form the stalk. Here, it is shown that if peptide binding changes kappa or some other combinations of local elastic constants by only tens of percents, the stalk energy and the energy of catenoidal fusion pores would decrease by tens of k(B)T relative to the pure lipid value. This is comparable to the required mediating effect. The curvature energies of stalks and catenoidal fusion pores have almost the same dependence on monolayer elastic constants as the curvature energies of the rhombohedral and Q(II) phases; respectively. The effects of isolated fusion-relevant peptides on the energies of these intermediates can be determined by studying the effects of the peptides on the stability of rhombohedral and Q(II) phases. | 18,805,927 |
Atypical object exploration at 12 months of age is associated with autism in a prospective sample. | This prospective study examined object exploration behavior in 66 12-month-old infants, of whom nine were subsequently diagnosed with an autism spectrum disorder. Previous investigations differ on when the repetitive behaviors characteristic of autism are first present in early development. A task was developed that afforded specific opportunities for a range of repetitive uses of objects and was coded blind to outcome status. The autism/ASD outcome group displayed significantly more spinning, rotating, and unusual visual exploration of objects than two comparison groups. The average unusual visual exploration score of the autism/ASD group was over four standard deviations above the mean of the group with no concerns at outcome. Repetitive behaviors at 12 months were significantly related to cognitive and symptomatic status at 36 month outcome. These results suggest that repetitive or stereotyped behaviors may be present earlier than initially thought in very young children developing the autism phenotype. | 18,805,942 |
Distinct roles for Khd1p in the localization and expression of bud-localized mRNAs in yeast. | The RNA-binding protein Khd1p (KH-domain protein 1) is required for efficient localization of ASH1 mRNA to the bud-tip, probably acting as a translational repressor during mRNA transport in yeast. Here, we have systematically examined Khd1p mRNA targets and colocalization with known bud-tip-localized mRNAs in vivo. Affinity purification and DNA microarray analysis of Khd1p-associated mRNAs revealed hundreds of potential mRNAs targets, many of them encoding membrane-associated proteins. The putative targets include the messages for MID2, MTL1, WSC2, SRL1, EGT2, CLB2, ASH1, and Khd1p colocalizes with these mRNAs at the bud-tip. The combination of bioinformatics, RNA localization, and in vitro RNA-binding assays revealed that Khd1p binds to CNN repeats in coding regions of mRNA targets. Among the proteins encoded by previously known bud-tip-localized mRNAs, only Mtl1p levels were decreased in khd1Delta mutant cells, whereas Ash1p and Srl1p were reduced in cells overexpressing KHD1. Hence, Khd1p differentially affects gene expression possibly due to combinatorial arrangement with additional factors reflecting the redundant structure of post-transcriptional regulatory systems. | 18,805,955 |
Effects of distension on airway inflammation and venular P-selectin expression. | We previously have shown in mice and rats, enhanced leukocyte recruitment to airway postcapillary venules after excessive distention imposed by the application of positive end-expiratory pressure. Because P-selectin was shown to be essential for this outcome, we sought to establish an in vitro endothelial cell model and determine the mechanisms whereby mechanical distension alters adhesion molecule expression. P-selectin surface expression on mouse jugular vein endothelial cells exposed to cyclic stretch (5 or 20% elongation for 5 min; Flexercell) were compared with static cells. The larger, pathophysiological regimen of cyclic stretch showed a 54% increase in P-selectin expression after stretch compared with static cells. This response was attenuated but confirmed in tracheal venular endothelium (29% increase). We questioned whether these changes were dependent on increases in intracellular Ca(2+) through voltage-gated Ca(2+) channels. The stretch-induced increase in P-selectin expression was substantially decreased by pretreatment with the T-type Ca(2+) channel inhibitor mibefradil (76% inhibition). Furthermore, when the Ca(v)3.1 T-type Ca(2+) channel expression was decreased in both endothelial cell subtypes with specific small-interfering RNA, the distension-induced expression of P-selectin decreased to levels less than that observed in static cells. We conclude that P-selectin expression on systemic venular endothelial cells contributes to a proinflammatory phenotype after mechanical stretch and can be selectively modulated by voltage-gated calcium channel inhibition. | 18,805,956 |
Pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recombinant asparaginase preparation in children with previously untreated acute lymphoblastic leukemia: a randomized phase 2 clinical trial. | The pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recombinant Escherichia coli-asparaginase preparation was compared with Asparaginase medac. Thirty-two children with acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5000 U/m(2) every 3 days, for a total of 8 doses during induction treatment. The serum activity-time profile after the first dose of recombinant asparaginase was similar to that of Asparaginase medac. The trough serum activities were greater than the desired threshold of 100 U/L in both treatment groups. Asparagine was completely depleted in serum and in cerebrospinal fluid, whereas glutamine levels were only moderately influenced. No significant difference between the 2 treatments regarding the degree of asparagine depletion, duration of depletion, complete remission rate, and minimal residual disease status at the end of induction, overall frequency or intensity of adverse events was seen. Observed adverse reactions are known as possible and labeled side effects of asparaginase treatment and chemotherapy. We conclude that the new recombinant asparaginase and other native Asparaginase medac are bioequivalent and have the same pharmacodynamic effects and the same direct toxicity profile in children with acute lymphoblastic leukemia. This trial was registered at http://www.controlled-trials.com as no. ISRCTN 75734403. | 18,805,963 |
Posttranslational modification influences the effects of MgrA on norA expression in Staphylococcus aureus. | MgrA is a global regulator in Staphylococcus aureus. Differences in the effects of MgrA on norA expression have been reported for different strains, which varied in rsbU, a gene that affects the expression of sigB, which encodes an alternative sigma factor involved in stress responses. We hypothesized that MgrA was modified by sigB-dependent factors that affected its ability to control the expression of the norA efflux pump. Heterologously expressed MgrA purified from Escherichia coli was incubated with crude extracts (CE) from strains RN6390 (rsbU) and SH1000 (rsbU(+)) and tested for binding to the norA promoter. Purified MgrA exhibited greater binding to norA promoter DNA after being incubated with SH1000 CE than MgrA incubated with the RN6390 CE. Phosphorylation of MgrA occurring in cell extracts caused it to lose the ability to bind norA promoter DNA. Overexpression of pknB, encoding a candidate serine/threonine kinase, produced increased phospho-MgrA and led to a fivefold increase in the transcript level of norA for both RN6390 and SH1000, as well as a fourfold increase in the MICs of norfloxacin and ciprofloxacin for these two strains. The levels of expression of pknB in RN6390 and SH1000, however, indicated that additional factors related to rsbU or sigB contribute to the differential regulatory effects of MgrA on norA expression. | 18,805,983 |
Transcriptional regulation of the citrate gene cluster of Enterococcus faecalis Involves the GntR family transcriptional activator CitO. | The genome of the gram-positive bacterium Enterococcus faecalis contains the genes that encode the citrate lyase complex. This complex splits citrate into oxaloacetate and acetate and is involved in all the known anaerobic bacterial citrate fermentation pathways. Although citrate fermentation in E. faecalis has been investigated before, the regulation and transcriptional pattern of the cit locus has still not been fully explored. To fill this gap, in this paper we demonstrate that the GntR transcriptional regulator CitO is a novel positive regulator involved in the expression of the cit operons. The transcriptional analysis of the cit clusters revealed two divergent operons: citHO, which codes for the transporter (citH) and the regulatory protein (citO), and upstream from it and in the opposite direction the oadHDB-citCDEFX-oadA-citMG operon, which includes the citrate lyase subunits (citD, citE, and citF), the soluble oxaloacetate decarboxylase (citM), and also the genes encoding a putative oxaloacetate decarboxylase complex (oadB, oadA, oadD and oadH). This analysis also showed that both operons are specifically activated by the addition of citrate to the medium. In order to study the functional role of CitO, a mutant strain with an interrupted citO gene was constructed, causing a total loss of the ability to degrade citrate. Reintroduction of a functional copy of citO to the citO-deficient strain restored the response to citrate and the Cit(+) phenotype. Furthermore, we present evidence that CitO binds to the cis-acting sequences O(1) and O(2), located in the cit intergenic region, increasing its affinity for these binding sites when citrate is present and allowing the induction of both cit promoters. | 18,805,984 |
TAp73 knockout shows genomic instability with infertility and tumor suppressor functions. | The Trp53 gene family member Trp73 encodes two major groups of protein isoforms, TAp73 and DeltaNp73, with opposing pro- and anti-apoptotic functions; consequently, their relative ratio regulates cell fate. However, the precise roles of p73 isoforms in cellular events such as tumor initiation, embryonic development, and cell death remain unclear. To determine which aspects of p73 function are attributable to the TAp73 isoforms, we generated and characterized mice in which exons encoding the TAp73 isoforms were specifically deleted to create a TAp73-deficient (TAp73(-/-)) mouse. Here we show that mice specifically lacking in TAp73 isoforms develop a phenotype intermediate between the phenotypes of Trp73(-/-) and Trp53(-/-) mice with respect to incidence of spontaneous and carcinogen-induced tumors, infertility, and aging, as well as hippocampal dysgenesis. In addition, cells from TAp73(-/-) mice exhibit genomic instability associated with enhanced aneuploidy, which may account for the increased incidence of spontaneous tumors observed in these mutants. Hence, TAp73 isoforms exert tumor-suppressive functions and indicate an emerging role for Trp73 in the maintenance of genomic stability. | 18,805,989 |
A protracted and dynamic maturation schedule underlies Arabidopsis leaf development. | Leaf development has been monitored chiefly by following anatomical markers. Analysis of transcriptome dynamics during leaf maturation revealed multiple expression patterns that rise or fall with age or that display age-specific peaks. These were used to formulate a digital differentiation index (DDI) based on a set of selected markers with informative expression during leaf ontogeny. The leaf-based DDI reliably predicted the developmental state of leaf samples from diverse sources and was independent of mitotic cell division transcripts or propensity of specific cell types. When calibrated by informative root markers, the same algorithm accurately diagnosed dissected root samples. We used the DDI to characterize plants with reduced activities of multiple CINCINNATA (CIN)-TCP (TEOSINTE BRANCHED1, CYCLOIDEA, PCF) growth regulators. These plants had giant curled leaves made up of small cells with abnormal shape, low DDI scores, and low expression of mitosis markers, depicting the primary role of CIN-TCPs as promoters of differentiation. Delayed activity of several CIN-TCPs resulted in abnormally large but flat leaves with regular cells. The application of DDI has therefore portrayed the CIN-TCPs as heterochronic regulators that permit the development of a flexible and robust leaf form through an ordered and protracted maturation schedule. | 18,805,992 |
Identification of Campylobacter jejuni proteins recognized by maternal antibodies of chickens. | Campylobacter jejuni is one of the leading bacterial causes of food-borne gastroenteritis. Infection with C. jejuni is frequently acquired through the consumption of undercooked poultry or foods cross-contaminated with raw poultry. Given the importance of poultry as a reservoir for Campylobacter organisms, investigators have performed studies to understand the protective role of maternal antibodies in the ecology of Campylobacter colonization of poultry. In a previous study, chicks with maternal antibodies generated against the S3B strain of C. jejuni provided protection against Campylobacter colonization (O. Sahin, N. Luo, S. Huang, and Q. Zhang, Appl. Environ. Microbiol. 69:5372-5379, 2003). We obtained serum samples, collectively referred to as the C. jejuni S3B-SPF sera, from the previous study. These sera were determined to contain maternal antibodies that reacted against C. jejuni whole-cell lysates as judged by enzyme-linked immunosorbent assay. The antigens recognized by the C. jejuni S3B-SPF antibodies were identified by immunoblot analysis, coupled with mass spectrometry, of C. jejuni outer membrane protein extracts. This approach led to the identification of C. jejuni proteins recognized by the maternal antibodies, including the flagellin proteins and CadF adhesin. In vitro assays revealed that the C. jejuni S3B-SPF sera retarded the motility of the C. jejuni S3B homologous strain but did not retard the motility of a heterologous strain of C. jejuni (81-176). This finding provides a possible mechanism explaining why maternal antibodies confer enhanced protection against challenge with a homologous strain compared to a heterologous strain. Collectively, this study provides a list of C. jejuni proteins against which protective antibodies are generated in hens and passed to chicks. | 18,805,999 |
The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. | Acute hypertension during cardiac surgery can be difficult to manage and may adversely affect patient outcomes. Clevidipine is a novel, rapidly acting dihydropyridine L-type calcium channel blocker with an ultrashort half-life that decreases arterial blood pressure (BP). The Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events trial (ECLIPSE) was performed to compare the safety and efficacy of clevidipine (CLV) with nitroglycerin (NTG), sodium nitroprusside (SNP), and nicardipine (NIC) in the treatment of perioperative acute hypertension in patients undergoing cardiac surgery. We analyzed data from three prospective, randomized, open-label, parallel comparison studies of CLV to NTG or SNP perioperatively, or NIC postoperatively in patients undergoing cardiac surgery at 61 medical centers. Of the 1964 patients enrolled, 1512 met postrandomization inclusion criteria of requiring acute treatment of hypertension based on clinical criteria. The patients were randomized 1:1 for each of the three parallel comparator treatment groups. The primary outcome was the incidence of death, myocardial infarction, stroke or renal dysfunction at 30 days. Adequacy and precision of BP control was evaluated and is reported as a secondary outcome. There was no difference in the incidence of myocardial infarction, stroke or renal dysfunction for CLV-treated patients compared with the other treatment groups. There was no difference in mortality rates between the CLV, NTG or NIC groups. Mortality was significantly higher, though, for SNP-treated patients compared with CLV-treated patients (P=0.04). CLV was more effective compared with NTG (P=0.0006) or SNP (P=0.003) in maintaining BP within the prespecified BP range. CLV was equivalent to NIC in keeping patients within a prespecified BP range; however, when BP range was narrowed, CLV was associated with fewer BP excursions beyond these BP limits compared with NIC. CLV is a safe and effective treatment for acute hypertension in patients undergoing cardiac surgery. | 18,806,012 |
Pharmacokinetics of levobupivacaine (2.5 mg/kg) after caudal administration in children younger than 3 years. | Caudal administration of levobupivacaine (2.5 mg/kg) in children is used frequently in some hospitals. However, no reports of levobupivacaine concentrations have been published with this dosing scheme. We report the results of a study on the pharmacokinetics of levobupivacaine (2.5 mg/kg) after caudal administration in children younger than 3 yr. Ten children, aged 1-36 mo and scheduled for subumbilical surgery were studied under sevoflurane anesthesia. After caudal injection of 0.25% levobupivacaine (2.5 mg/kg), serial venous blood samples were taken for 3 h to measure total plasma concentration levels of levobupivacaine. Median (range) levobupivacaine Cmax and Tmax measured were 1.48 (0.62-2.40) microg/mL and 37 (10-60) min. The highest individual Cmax was observed in a 1-mo-old infant 30 min after caudal block. The highest Cmax reached in this study was close to the toxic threshold of adult patients. Although no adverse events have been reported, care must be taken, especially in small infants, after caudal administration of levobupivacaine (2.5 mg/kg). | 18,806,025 |
The accuracy and clinical feasibility of a new bayesian-based closed-loop control system for propofol administration using the bispectral index as a controlled variable. | Closed-loop control of the hypnotic component of anesthesia has been proposed in an attempt to optimize drug delivery. Here, we introduce a newly developed Bayesian-based, patient-individualized, model-based, adaptive control method for bispectral index (BIS) guided propofol infusion into clinical practice and compare its accuracy and clinical feasibility under direct observation of an anesthesiologist versus BIS guided, effect compartment controlled propofol administration titrated by the anesthesiologist during ambulatory gynecological procedures. Forty ASA patients were randomly allocated to the closed-loop or manual control group. All patients received midazolam 1 mg IV and alfentanil 0.5 mg IV before induction. In the closed-loop control group, propofol was administered using the previously described closed-loop control system to reach and maintain a target BIS of 50. In the manual control group, the propofol effect-site concentration was adapted at the discretion of the anesthesiologist to reach and maintain a BIS as close as possible to 50. Induction characteristics, performance, and robustness during maintenance and recovery times were compared. Hemodynamic and respiratory stability were calculated as clinical feasibility parameters. The closed-loop control system titrated propofol administration accurately resulting in BIS values close to the set point. The closed-loop control system was able to induce the patients within clinically accepted time limits and with less overshoot than the manual control group. Automated control resulted in beneficial recovery times. Our closed-loop control group showed similar acceptable clinical performance specified by similar hemodynamic, respiratory stability, comparable movement rates, and quality scores than the manual control group. The Bayesian-based closed-loop control system for propofol administration using the BIS as a controlled variable performed accurate during anesthesia for ambulatory gynecological procedures. This control system is clinical feasibility and can be further validated in clinical practice. | 18,806,028 |
The risk of pulmonary aspiration in patients after weight loss due to bariatric surgery. | We conducted a study including patients with gastric banding or gastroplasty who previously underwent plastic or functional surgery to assess the risk of pulmonary aspiration. A retrospective case-control study was performed including all patients undergoing a plastic or functional surgery over a 5-yr period (2000-2005) at Rouen University Hospital. Two groups were defined: the postbariatric group included patients who previously had bariatric surgery (laparoscopic adjustable gastric banding or Mason's vertical gastroplasty) before undergoing the plastic surgery; all other patients were assigned to the control group. Data included all anesthetic management and were recorded in the hospital computer database. The incidence of pulmonary aspiration was the outcome variable. One hundred ninety-eight plastic and functional operations (66 cases and 132 controls) were performed. Pulmonary aspiration was significantly (P<0.006) higher in the postbariatric group (4 patients: 6%) than in the nonbariatric group (0 patient). For this complication, all patients had previously undergone gastric banding. One patient who did not receive prokinetic prophylaxis required intensive care for severe pulmonary alteration. The risk of perioperative pulmonary aspiration in a patient after weight loss due to gastric banding was considered significant. | 18,806,037 |
Perioperative management of patients with an intrathecal drug delivery system for chronic pain. | The use of intrathecal medications in the treatment of chronic pain is becoming more commonplace. As such, the incidence of encountering patients receiving therapy via an intrathecal drug delivery system in the perioperative period will also increase. In this case series, we discuss anesthetic management and postoperative analgesic issues in three patients with indwelling intrathecal drug delivery systems placed for treatment of chronic pain. | 18,806,058 |
The effect of injectate conductivity on the electric field with the nerve stimulator needle: a computer simulation. | Electrical neural stimulation is commonly used to localize neural structures and place local anesthetic for regional anesthesia. The sharp tip of the stimulating needle gives rise to an electric field which is highly localized. The electrostatic effect of the injected solution on the field distribution and strength has not previously been modeled. The three-dimensional electric field around a 0.7 mm diameter, un-insulated, hollow needle with a 30 degrees bevel was calculated in silico using a hybrid finite difference/impedance network method to solve the Laplace equation. The surrounding tissue was assumed to be electrically uniform. A sphere of injectate centered on the bevel was modeled as a region of conductivity differing from that of the bulk tissue. The electric field strength was highly concentrated at the needle tip and decayed rapidly with distance r approximately as 1/r1.7. It was demonstrated that the electric field in the immediate vicinity of the needle tip was greatly reduced in the presence of solutions with conductivity greater than that of the surrounding tissue. A 1.5 mm radius region of conducting solution (equivalent to saline or local anesthetics) reduced the field by 31%. The same volume of a relatively insulating injectate, such as dextrose solution, led to a field enhancement of approximately 15%. The electric field magnitude in the vicinity of the needle tip decayed more slowly with distance than predicted by Coulomb's law. This was independent of the presence of injectate. The near instantaneous abolition of muscle twitch with injection of small volumes of local anesthetic is consistent with an electrostatic effect, rather than a pharmacological or mechanical one. The change in field strength depended upon the volume of the injectate and its conductivity relative to that of the surrounding tissue. In this simulation, even tiny volumes of injectate lead to significant changes in field and therefore threshold current, which may have clinical implications. | 18,806,064 |
Urethral injury during potassium-titanyl-phosphate laser prostatectomy complicated by transurethral resection syndrome. | The green light potassium-titanyl-phosphate laser photoselective vaporization of the prostate is the latest modality for treatment of benign prostatic obstruction. Because of effective superficial tissue coagulation, intravascular absorption of fluid is minimal; therefore, development of transurethral resection syndrome is unlikely. To our knowledge, this is the first report of a patient undergoing photoselective vaporization of the prostate who developed full-blown transurethral resection syndrome because of intravascular absorption of sterile water. Absorption of hypotonic irrigant presumably occurred through the injury induced during insertion of the laser cystoscope. | 18,806,066 |
Statins and sepsis: good bullet, disappearing target. | Despite several decades of research and phenomenal advances in technology and therapeutics, sepsis remains a catastrophic enigma. As a frequent cause of death, sepsis now rivals acute myocardial infarction. The longstanding therapeutic principles of early antibiotics use and supportive care have been difficult to improve upon. The authors conducted a concise review of pertinent literature on the pathophysiologic mechanisms of sepsis and the pharmacologic effects of statins. They conclude that, though statins possess anti-inflammatory and lipid-lowering properties, these effects may not be advantageous throughout the changing immunoresponse that can occur in sepsis syndrome. Based on the available information, statin therapy seems advantageous before the onset of sepsis and during sepsis resolution--but not during the compensatory anti-inflammatory response that may occur. Thus, the authors recommend that, until the status of a patient's changing immune response can be clearly determined, the uninterrupted use of statin therapy throughout the full spectrum of sepsis should be avoided. | 18,806,077 |
Postpartum thyroid measures and depressive symptomology: a pilot study. | While correlations have been demonstrated between postpartum depression and psychosocial and circumstantial risk factors, some evidence exists for a similar relationship between postpartum depression and thyroid measures. To search at 4 weeks postpartum for correlations of numerical scores on a postnatal depression screening tool and thyroid measures. Subjects took the Edinburgh Postnatal Depression Scale (EPDS) prenatally and at 4 weeks postpartum. Participants were also given blood tests for thyroid-stimulating hormone (TSH), free thyroxine4, thyroid peroxidase, and thyroglobulin at the same testing intervals. Fifty-one subjects aged 18 years or older were recruited. Subjects with higher serum TSH at 4 weeks postpartum tended to have higher EPDS scores. Similarly, the 7 subjects (13.7%) with positive postnatal thyroid antibody tests were more likely than their counterparts to have higher EPDS scores. Presence of thyroid autoantibodies or higher TSH levels during the postpartum period may be related to depressive symptoms or dysphoric mood, even when clinical depression is not present. Either or both of these associations may contribute, along with other physiologic and psychosocial risk factors, to postpartum depression. (ClinicalTrials.gov number NCT00565032). | 18,806,079 |
Incidental pleural-based pulmonary lymphangioma. | Adult benign thoracic lymphangiomas typically present as incidental mediastinal lesions, or, more rarely, as solitary pulmonary nodules. Symptomatic compression of vital structures may require lesion resection or sclerotherapy. In the present report, we describe the incidental finding of a solitary pleural-based pulmonary lymphangioma in a 38-year-old woman with chronic arm and shoulder pain. Positron emission tomography revealed that the lesion was highly fluorodeoxyglucose-avid. Biopsy exposed benign tissue consistent with lymphangioma. After continued radiographic tests, the lesion was determined to be an unlikely source of the patient's chronic pain. The present report is, to our knowledge, the first published case of solitary pleural-based pulmonary lymphangioma in the medical literature. | 18,806,082 |
Clinical use of glutamine supplementation. | Endogenous production of glutamine may become insufficient during critical illness. The shortage of glutamine is reflected as a decrease in plasma concentration, which is a prognostic factor for poor outcome in sepsis. Because glutamine is a precursor for nucleotide synthesis, rapidly dividing cells are most likely to suffer from a shortage. Therefore, exogenous glutamine supplementation is necessary. In particular, when i.v. nutrition is given, extra glutamine supplementation becomes critical, because most present formulations for i.v. use do not contain any glutamine for technical reasons. The major part of endogenously produced glutamine comes from skeletal muscle. For patients staying a long time in the intensive care unit (ICU), the muscle mass decreases rapidly, which leaves a tissue of diminishing size to maintain the export of glutamine. The metabolic and nutritional adaptation in long-staying ICU patients is poorly studied and is one of the fields that needs more scientific evidence for clinical recommendations. To date, there is evidence to support the clinical use of glutamine supplementation in critically ill patients, in hematology patients, and in oncology patients. Strong evidence is presently available for i.v. glutamine supplementation to critically ill patients on parenteral nutrition. This must be regarded as the standard of care. For patients on enteral nutrition, more evidence is needed. To guide administration of glutamine, there are good arguments to use measurement of plasma glutamine concentration for guidance. This will give an indication for treatment as well as proper dosing. Most patients will have a normalized plasma glutamine concentration by adding 20-25 g/24 h. Furthermore, there are no reported adverse or negative effects attributable to glutamine supplementation. | 18,806,121 |
Radiodefluorination of 3-fluoro-5-(2-(2-[18F](fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile ([18F]SP203), a radioligand for imaging brain metabotropic glutamate subtype-5 receptors with positron emission tomography, occurs by glutathionylation in rat brain. | Metabotropic glutamate subtype-5 receptors (mGluR5) are implicated in several neuropsychiatric disorders. Positron emission tomography (PET) with a suitable radioligand may enable monitoring of regional brain mGluR5 density before and during treatments. We have developed a new radioligand, 3-fluoro-5-(2-(2-[(18)F](fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile ([(18)F]SP203), for imaging brain mGluR5 in monkey and human. In monkey, radioactivity was observed in bone, showing release of [(18)F]-fluoride ion from [(18)F]SP203. This defluorination was not inhibited by disulfiram, a potent inhibitor of CYP2E1. PET confirmed bone uptake of radioactivity and therefore defluorination of [(18)F]SP203 in rats. To understand the biochemical basis for defluorination, we administered [(18)F]SP203 plus SP203 in rats for ex vivo analysis of metabolites. Radio-high-performance liquid chromatography detected [(18)F]fluoride ion as a major radiometabolite in both brain extract and urine. Incubation of [(18)F]SP203 with brain homogenate also generated this radiometabolite, whereas no metabolism was detected in whole blood in vitro. Liquid chromatography-mass spectrometry analysis of the brain extract detected m/z 548 and 404 ions, assignable to the [M + H](+) of S-glutathione (SP203Glu) and N-acetyl-S-l-cysteine (SP203Nac) conjugates of SP203, respectively. In urine, only the [M + H](+) of SP203Nac was detected. Mass spectrometry/mass spectrometry and multi-stage mass spectrometry analyses of each metabolite yielded product ions consistent with its proposed structure, including the former fluoromethyl group as the site of conjugation. Metabolite structures were confirmed by similar analyses of SP203Glu and SP203Nac, prepared by glutathione S-transferase reaction and chemical synthesis, respectively. Thus, glutathionylation at the 2-fluoromethyl group is responsible for the radiodefluorination of [(18)F]SP203 in rat. This study provides the first demonstration of glutathione-promoted radiodefluorination of a PET radioligand. | 18,806,125 |
MRI appearance of posterior cruciate ligament tears. | There is little in the radiology literature regarding the MRI appearance of a torn posterior cruciate ligament (PCL). The purpose of this study was to describe the MRI appearance of surgically proven PCL tears and to emphasize previously unreported signs. The PCL is usually injured as the result of stretching deformation; on MRI, the ligament maintains continuity as a single structure with apparent thickening. On sagittal T2-weighted images, an anteroposterior diameter of 7 mm or more is highly suggestive of a torn PCL. Increased intrasubstance signal intensity in the PCL on proton-density images with lower signal intensity on T2-weighted images is another common feature. | 18,806,138 |
Feasibility of MRI of the fetal heart with balanced steady-state free precession sequence along fetal body and cardiac planes. | The purpose of this study was to evaluate the feasibility of imaging the fetal heart with a balanced steady-state free precession MRI sequence along the body and cardiac axes after inadequate echocardiography. After technically inadequate echocardiography, MRI was performed on 20 fetuses (mean gestational age, 24 weeks; range, 18-32 weeks) at risk of congenital heart disease. MRI was attempted along the three fetal body planes (n = 20) and cardiac axes (n = 3) without fetal sedation. The images were analyzed with an anatomic segmental approach. Each feature was classified as well visualized or poorly or not visualized. In each group, the Student's t test was used to assess the relation between visibility of fetal cardiac features and gestational age. Imaging was possible along the fetal body and cardiac axes. In the axial plane, a balanced four-chamber view was obtained in all fetuses, enabling evaluation of heart position, axis, chambers, and interventricular septum. The left and right ventricular outflow tracts were well visualized in 12 (60%) and nine (45%) of the fetuses, respectively; the three-vessel view was obtained in 10 fetuses (50%). With the combination of sagittal and coronal views, both ventricular outflow tracts were assessed in all fetuses. The superior and inferior venae cavae were identified in all fetuses, and at least one pulmonary vein was visualized in 17 fetuses (85%). There were no statistically significant differences between gestational age and lack of visualization of a cardiac feature that was attributed to fetal motion. MRI of the fetal heart with a steady-state free precession sequence in multiple planes and image analysis with an anatomic segmental approach to congenital heart disease are possible in situations that limit echocardiography. | 18,806,167 |
Comparison of contrast-enhanced sonography with unenhanced sonography and contrast-enhanced CT in the diagnosis of malignancy in complex cystic renal masses. | The objective of our study was to evaluate contrast-enhanced sonography in the diagnosis of malignancy in complex cystic renal masses. We analyzed a series of 40 cystic renal masses (diameter, 2-8 cm) with a complex pattern at contrast-enhanced CT in 40 consecutive subjects (18 men, 22 women; mean age +/- SD, 62 +/- 11 years). Each renal mass was scanned using sonography without contrast material and after IV injection of sulfur hexafluoride-filled microbubbles during the arterial (15-40 seconds) and venous (40-120 seconds from injection) phases. Two radiologists in consensus assessed onsite the enhancement patterns in the peripheral wall and intracystic septa and the evidence of solid endocystic components. Three blinded readers with 2, 6, and 10 years of experience in renal imaging performed a retrospective off-site interpretation of unenhanced sonography, contrast-enhanced sonography, and CT images and made a benign or malignant diagnosis according to refer ence diagnostic criteria for contrast-enhanced sonography and to the Bosniak classification for CT. Final diagnoses comprised two multilocular cystic nephromas, two inflammatory and seven hemorrhagic cysts, and eight uncomplicated benign cysts and 21 cystic renal cell carcinomas. The overall diagnostic accuracy of contrast-enhanced sonography was better than unenhanced sonography and CT (contrast-enhanced sonography vs unenhanced sonography vs CT: reader 1, 83% vs 30% vs 75%; reader 2, 83% vs 30% vs 63%; reader 3, 80% vs 30% vs 70%; p < 0.05, McNemar test). Contrast-enhanced sonography was found to be better than unenhanced sonography and CT in the diagnosis of malignancy in complex cystic renal masses. | 18,806,171 |
'They're more like ordinary stroppy British women': attitudes and expectations of maternity care professionals to UK-born ethnic minority women. | To explore the attitudes and expectations of maternity care professionals to UK-born ethnic minority mothers. Qualitative in-depth interviews with 30 professionals from eight NHS maternity units in England that provide services for large proportions of women of black Caribbean, black African, Indian, Pakistani and Irish descent. All the professionals reported providing care to both UK-born and migrant mothers from ethnic minorities. Most of them felt that they could differentiate between UK-born and migrant mothers based mainly on language fluency and accent. 'Westernized dress' and 'freedom' were also cited as indicators. Overall, professionals found it easier to provide services to UK-born mothers and felt that their needs were more like those of white English mothers than those of migrant mothers. UK-born mothers were generally thought to be assertive and expressive, and in control of care-related decision-making whereas some South Asian Muslim women were thought to be constrained by family influences. Preconceived ideas about ethnic minority mothers' tolerance of pain in labour, use of pharmacological pain relief measures and mode of delivery were recurring themes. Women's education and social class were felt to be major influences on the uptake of maternity care, regardless of ethnicity. Professionals appeared to equate the needs of UK-born ethnic minority women with those of white English women. Overall, this has positive implications for care provision. Despite this, specific behavioural expectations and unconscious stereotypical views were evident and have the potential to affect clinical practice. | 18,806,176 |
Factors contributing to nursing leadership: a systematic review. | Leadership practices of health care managers can positively or negatively influence outcomes for organizations, providers and, ultimately, patients. Understanding the factors that contribute to nursing leadership is fundamental to ensuring a future supply of nursing leaders who can positively influence outcomes for health care providers and patients. The purpose of this study was to systematically review the multidisciplinary literature to examine the factors that contribute to nursing leadership and the effectiveness of educational interventions in developing leadership behaviours among nurses. The search strategy began with 10 electronic databases (e.g. CINAHL, Medline). Published quantitative studies were included that examined the factors that contribute to leadership or the development of leadership behaviours in nurse leaders. Quality assessments, data extraction and analysis were completed on all included studies. A total of 27,717 titles/abstracts were screened resulting in 26 included manuscripts reporting on 24 studies. Twenty leadership factors were examined and categorized into four groups - behaviours and practices of individual leaders, traits and characteristics of individual leaders, influences of context and practice settings, and leader participation in educational activities. Specific behaviours and practices of individual leaders, such as taking on or practising leadership styles, skills and roles, were reported as significantly influencing leadership in eight studies. Traits and characteristics of individual leaders were examined in six studies with previous leadership experience (three studies) and education levels (two of three studies) having positive effects on observed leadership. Context and practice settings had a moderate influence on leadership effectiveness (three of five studies). Nine studies that examined participation in leadership development programs all reported significant positive influences on observed leadership. These findings suggest that leadership can be developed through specific educational activities, and by modelling and practising leadership competencies. However, the relatively weak study designs provide limited evidence for specific factors that could increase the effectiveness of current nursing leadership or guide the identification of future nurse leaders. Robust theory and research on interventions to develop and promote viable nursing leadership for the future are needed to achieve the goal of developing healthy work environments for health care providers and optimizing care for patients. | 18,806,183 |
What leads to better health care innovation? Arguments for an integrated policy-oriented research agenda. | This essay is based on the recognition that the current 'downstream' health services research and policy approach to innovation misses the mark on one crucial point. It has not addressed how to promote the design of innovations that are likely to be more valuable than others. Re-visiting the ways in which health services research could inform innovation processes, this paper suggests that three attributes make innovations especially compelling from a health care system perspective: relevance; usability; and sustainability. These could be used as a starting point for outlining a policy-oriented research agenda that could bridge upstream design processes, and downstream needs and priorities. Given the pace at which innovations come about and the complexity of health care systems, we believe that both research and policy should be able to contribute significantly to the shaping of socially valuable technological change in health care. Recognizing that such a long-term goal cannot be reached through a linear, rationalistic process, our paper offers preliminary arguments to start to reconcile the health policy and innovation agendas. | 18,806,185 |
MOBILE and the provision of total joint replacement. | Modern joint replacements have been available for 45 years, but we still do not have clear indications for these interventions, and we do not know how to optimize the outcome for patients who agree to have them done. The MOBILE programme has been investigating these issues in relation to primary total hip and knee joint replacements, using mixed methods research. There have been five main strands: (1) Epidemiological investigations to find out who is receiving total hip and knee replacements in the National Health Service (NHS). This has shown that there are extensive variations in different regions of the UK, with inequalities and probable inequities in the provision of these operations; (2) Epidemiological work to ascertain the population-based needs for the operations, showing under-provision of knee joint replacements, and a relative reluctance of both patients and GPs to consider knee surgery; (3) Quantitative and qualitative research into the views of patients, health care professionals and the public on the indications for, and prioritization of, total hip and knee joint replacements. This has shown lack of agreement within or between professional groups, as well as a mismatch between the views of patients and the public, and those of professionals; (4) Theoretical and experimental work on patient-related outcome measures, and the development of new instruments to assess both pain and function in people with osteoarthritis, based on the International Classification of Function, as well as a new integrated model of function; (5) Cohort studies of patients undergoing hip or knee joint replacements to find out what the determinants of good and bad outcomes are. These studies have emphasized the huge variation in disease severity at the time of surgery. The challenge now is to use and implement our findings for maximum patient benefit. | 18,806,192 |
Endovenous laser ablation: mechanism of action. | The objective of this study is to review the basics of laser and established tissue response patterns to thermal injury, with specific reference to endovenous laser ablation (EVLA). This study also reviews the current theories and supporting aspects for the mechanism of action of EVLA in the treatment of superficial venous reflux. The method involves the review of published literature and original investigation of histological effects of 810 nm and 980 nm wavelength EVLA on explanted blood-filled bovine saphenous vein in an in vitro system. The existing histological reports confirm that EVLA produces a transmural vein wall injury, typically associated with perforations and carbonization. The pattern of injury is eccentrically distributed, with maximum injury occurring along the path of laser contact. Intravenous temperature monitoring studies during EVLA have confirmed that the peak temperatures at the fibre tip exceed 1000 degrees C, and continuous temperatures of at least 300 degrees C are maintained in the firing zone for the majority of the procedure. Steam production during EVLA, which occurs early in the photothermolytic process when temperatures reach 100 degrees C, accounts for only 2% of applied energy dose, and is therefore unlikely to be the primary mechanism of action of thermal injury during the procedure. EVLA causes permanent vein closure through a high-temperature photothermolytic process at the point of contact between the vein and the laser. | 18,806,202 |
Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger. | A recessive phenotype called spin (spontaneous inflammation) was induced by N-ethyl-N-nitrosourea (ENU) mutagenesis in C57BL/6J mice. Homozygotes display chronic inflammatory lesions affecting the feet, salivary glands and lungs, and antichromatin antibodies. They are immunocompetent and show enhanced resistance to infection by Listeria monocytogenes. TLR-induced TNF and IL-1 production are normal in macrophages derived from spin mice. The autoinflammatory phenotype of spin mice is fully suppressed by compound homozygosity for Myd88(poc), Irak4(otiose), and Il1r1-null mutations, but not Ticam1(Lps2), Stat1(m1Btlr), or Tnf-null mutations. Both autoimmune and autoinflammatory phenotypes are suppressed when spin homozygotes are derived into a germ-free environment. The spin phenotype was ascribed to a viable hypomorphic allele of Ptpn6, which encodes the tyrosine phosphatase SHP1, mutated in mice with the classical motheaten alleles me and me-v. Inflammation and autoimmunity caused by SHP1 deficiency are thus conditional. The SHP1-deficient phenotype is driven by microbes, which activate TLR signaling pathways to elicit IL-1 production. IL-1 signaling via MyD88 elicits inflammatory disease. | 18,806,225 |
Disrupted development of the dominant hemisphere following prenatal irradiation. | One hundred children, exposed prenatally to radiation after the Chernobyl nuclear power plant accident, and 50 nonexposed classmates were examined between the ages of 11 and 13 years old using neuropsychiatric tests, WISC, EEG, and visual evoked potentials. Individual prenatal radiation doses were reconstructed for all examined children. The exposed children were found to have more neuropsychiatric disorders, left-brain neurological signs, lower full-scale and verbal IQ, IQ discrepancies with verbal decrement, disorganized EEG patterns, an excess of lateralized-to-left frontotemporal region delta and beta power with depression of theta and alpha power, and interhemispheric inversion visual information processing. Mothers' mental health, stress, and prenatal irradiation contributed to these effects, along with several confounding factors. | 18,806,231 |
Multiple protein domains mediate interaction between Bcl10 and MALT1. | Bcl10 and MALT1 are essential mediators of NF-kappaB activation in response to the triggering of a diverse array of transmembrane receptors, including antigen receptors. Additionally, both proteins are translocation targets in MALT lymphoma. Thus, a detailed understanding of the interaction between these mediators is of considerable biological importance. Previous studies have indicated that a 13-amino acid region downstream of the Bcl10 caspase recruitment domain (CARD) is responsible for interacting with the immunoglobulin-like domains of MALT1. We now provide evidence that the death domain of MALT1 and the CARD of Bcl10 also contribute to Bcl10-MALT1 interactions. Although a direct interaction between the MALT1 death domain and Bcl10 cannot be detected via immunoprecipitation, FRET data strongly suggest that the death domain of MALT1 contributes significantly to the association between Bcl10 and MALT1 in T cells in vivo. Furthermore, analysis of point mutants of conserved residues of Bcl10 shows that the Bcl10 CARD is essential for interaction with the MALT1 N terminus. Mutations that disrupt proper folding of the Bcl10 CARD strongly impair Bcl10-MALT1 interactions. Molecular modeling and functional analyses of Bcl10 point mutants suggest that residues Asp(80) and Glu(84) of helix 5 of the Bcl10 CARD directly contact MALT1. Together, these data demonstrate that the association between Bcl10 and MALT1 involves a complex interaction between multiple protein domains. Moreover, the Bcl10-MALT1 interaction is the second reported example of interactions between a CARD and a non-CARD protein region, which suggests that many signaling cascades may utilize CARD interactions with non-CARD domains. | 18,806,265 |
Circulating hematopoietic stem cells in patients with idiopathic choroidal neovascularization. | In a prior study, the correlation was investigated between circulating hematopoietic stem cells (HSCs) and the activity or severity of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). The present study was designed to explore the role of circulating HSCs in the pathogenesis of CNV in patients with idiopathic (i)CNV. Thirteen patients with clinically documented iCNV and 10 age-sex matched patients without iCNV or systemic disease were enrolled in a case-control study. Circulating HSCs were collected from the patients' peripheral blood and cultured. Colony-forming capacity, migration activity, and invasion activity of HSCs were experimentally analyzed. Colony-forming units by Hill's assay (CFU-Hill) were markedly lower (P<0.001) in patients with iCNV (12.8+/-3.2) than in healthy patients (67.6+/-12.6). Invasion activities of HSCs were reduced significantly in patients with iCNV. CFU-Hill was impaired in the patients (4.0+/-1.2) with CNV more than 1500 microm compared with the patients (20.3+/-4.0) with CNV less than 1500 microm (P=0.006). Similar to the previous finding of CNV associated with AMD, impaired functional activities of circulating HSCs were observed in patients with iCNV, which correlated with the size of iCNV. These results in young patients provide evidence to support the role of circulating HSCs in the pathogenesis of CNV. | 18,806,291 |
Suppression of influenza A virus nuclear antigen production and neuraminidase activity by a nutrient mixture containing ascorbic acid, green tea extract and amino acids. | Influenza, one of the oldest and most common infections, poses a serious health problem causing significant morbidity and mortality, and imposing substantial economic costs. The efficacy of current drugs is limited and improved therapies are needed. A unique nutrient mixture (NM), containing ascorbic acid, green tea extract, lysine, proline, N-acetyl cysteine, selenium among other micronutrients, has been shown to exert anti-carcinogenic and anti-atherogenic activity both in vitro and in vivo. Many of the constituents of NM have been shown to have an inhibitory effect on replication of influenza virus and HIV. This prompted us to study the effect of NM on influenza A virus multiplication in infected cells and neuraminidase activity (NA) in virus particles. Addition of NM to Vero or MDCK cells post infection resulted in dose-dependent inhibition of viral nucleoprotein (NP) production in infected cells. NM-mediated inhibition of viral NP was selective and not due to cytotoxicity towards host cells. This antiviral effect was enhanced by pretreatment of virus with the nutrient mixture. Individual components of NM, namely ascorbic acid and green tea extract, also blocked viral NP production, conferring enhanced inhibition when tested in combination. Incubation of cell-free virus with NM resulted in dose-dependent inhibition of associated NA enzyme activity. In conclusion, the nutrient mixture exerts an antiviral effect against influenza A virus by lowering viral protein production in infected cells and diminishing viral enzymatic activity in cell-free particles. | 18,806,304 |
Oxidation of glutathione and superoxide generation by inorganic and organic selenium compounds. | The carcinostatic activities of selenium (Se) compounds have been shown to be composition and concentration dependent. Several studies have indicated that the ratios between glutathione (GSH) and Se may play an important role in Se catalysis and toxicity. The present study examined the catalytic effect of three selenium compounds on GSH oxidation using lucigenin-dependent chemiluminescence (CL) as an indirect measure of superoxide generation. Various GSH:Se ratios were assayed for the glutathione oxidase activity of selenite, selenocystamine and diselenodipropionic acid. CL emitted from the reaction of selenite with GSH increased more rapidly and was greater than those from the diselenides, but the diselenide CL reactions were sustainable. Both selenite- and diselenide-induced CL were markedly suppressed by superoxide dismutase (SOD). Iodoacetic acid (IAc) effectively inhibited CL generated from selenite-, selenocystamine- and diselenodipropionic acid-catalyzed GSH oxidation. These results suggest that GSH oxidation catalyzed by selenite, and the diselenides selenocystamine and diselenodipropionic acid, generated the superoxide radical in which the CL was inhibited by SOD. Furthermore, CL inhibition by IAc suggests that the catalytic species producing superoxide were the GSSe(-) or RSe(-) anion. This redox chemistry may be responsible for selenite and organoselenium toxicity and apoptosis, making possible the design and synthesis of organoselenium-containing pharmaceuticals. | 18,806,309 |
Attenuation of mitochondrial injury by L-arginine preconditioning of the liver. | The present study was aimed to evaluate the efficacy of L-arginine on mitochondrial function in ischemic and reperfusion (I/R) induced hepatic injury. Adult Wistar rat were subjected to 1 h of partial liver ischemia followed by 3 hour reperfusion. Eighteen wistar rats were divided into three groups viz. sham-operated control group (I) (n=6), ischemia and reperfusion (I/R) group (II) (n=6), L-arginine treated group (100 mg/kg body weight/daily by oral route for 7 days before induced ischemia reperfusion maneuver) (III) (n=6). Mitochondrial injury was assessed in terms of decreased (P<0.05) activities of mitochondrial antioxidant enzymes (GSH, SOD, CAT), respiratory marker enzymes (NADH dehydrogenase, cytochrome c oxidases) and hepatocytes nitric oxide production. Pre-treatment with L-arginine (10 mg/kg/p.o. for 7 days) significantly counteracted the alternations of hepatic enzymes and mitochondrial respiratory and antioxidant enzymes. In addition, electron microscopy and histopathology study showed the restoration of cellular normalcy and accredits the cytoprotective role of L-arginine against I/R induced hepatocellular injury. On the basis of these findings it may be concluded that L-arginine protects mitochondrial function in hepatic ischemic and reperfused liver. | 18,806,313 |
Serum selenium concentration in healthy children living in Tehran. | Selenium is one of the essential trace elements which is more notified in children in recent years. Reliable age-specific reference values for selenium in children in Iran are not clear and are important for the identification of selenium deficiency and some other researches that is the aim of this study. Serum samples of 216 healthy children were analyzed by using hydride generation and flame atomic absorption spectroscopy to measured selenium level. The mean and standard deviation of serum selenium level in children 0-16 years old (mean: 39.83 months) was 72.14+/-16.80 microg/l. There was significant difference in serum selenium concentration between two sexes which was 76.78+/-15.24 microg/l and 69.56+/-17.09 microg/l in girls and boys respectively (P value=0.002). There was also a positive correlation between higher selenium serum concentration and age in both sexes. Essential trace element's normal ranges are fundamental data which could use in many studies. Serum selenium concentration in healthy Iranian children that found in this study is very close to serum concentration of European children. Our findings may reveal nutritional culture's similarity. | 18,806,316 |
Computer-Interpretable Guideline formalisms. | Implementing Computer-Interpretable Guidelines (CIGs) in active computer-based decision support systems promises to improve the acceptance and application of guidelines in daily practice. The model and underlying language are the core characteristics of every CIG approach. However, currently no standard model or language has been accepted by the CIG community. This aim of this chapter is to provide an overview of well-known approaches and to formulate a set of (minimal) requirements that can be used in the process of developing new CIG approaches or improving existing ones. It presents five CIG approaches (the Arden Syntax, GLIF, PROforma, Asbru and EON), followed by a general discussion of the strong points of each approach as well as their implications for future research. | 18,806,319 |
A constraint-based approach to medical guidelines and protocols. | Medical guidelines and protocols are documents aimed at improving the quality of medical care by offering support in medical decision making in the form of management recommendations based on scientific evidence. Whereas medical guidelines are intended for nation-wide use, and thus omit medical management details that may differ among hospitals, medical protocols are aimed at local use, e.g., within hospitals, and, therefore, include more detailed information. Although a medical guideline and an associated protocol concerning the management of a particular disorder are related to each other, one question is to what extent they are different. Formal methods are applied to shed light on this issue. A Dutch medical guideline regarding the treatment of breast cancer, and a Dutch protocol based on it, are taken as an example. | 18,806,330 |
A case of Legionella pneumophila pneumonia followed by invasive aspergillosis. | We report a rare case of Legionella pneumophila pneumonia followed by invasive aspergillosis (IA). Legionellosis was ameliorated by the administration of ciprofloxacin, erythromycin, and corticosteroid as adjunctive therapy. Although intravenous administration of the corticosteroid was effective at reducing severe inflammation due to legionellosis, IA occurred at 12 days after admission. Combination therapy with micafungin and voriconazole was effective in this case; however, it remains necessary to exercise caution when making decisions regarding indications for corticosteroid use and observation in the treatment of severe pneumonia patients. | 18,806,346 |
Risk factors for SARS infection within hospitals in Hanoi, Vietnam. | We investigated a nosocomial infection of severe acute respiratory syndrome (SARS) in Vietnam in 2003 and attempted to identify risk factors for SARS infection. Of the 146 subjects who came into contact with SARS patients at Hospital A, 43 (29.5%) developed SARS, and an additional 16 (11%) were asymptomatic but SARS-coronavirus (CoV) seropositive. The asymptomatic infection rate accounted for 15.5% of the total number of infected patients at Hospital A, which was higher than that of 6.5% observed at Hospital B, to where all patients from Hospital A were eventually transported (P<0.05). At Hospital A, the risk for developing SARS was 12.6 times higher in individuals not using a mask than in those using a mask. The SARS epidemic in Vietnam resulted in numerous secondary infections due to its unknown etiology and delayed recognition at the beginning of the epidemic. The consistent and proper use of a mask was shown to be crucial for constant protection against infection with SARS. | 18,806,349 |
Do serological tests provide adequate rapid diagnosis of Mycoplasma pneumoniae infection? | This study was designed to evaluate the serologic response to Mycoplasma pneumoniae infection. A total of 589 children < or =18 years (190 in the year 2004; 399 in 2005) and 2,073 adults > or = 18 years of age (980 in the year 2004; 1,093 in 2005) with respiratory symptoms underwent serological testing for M. pneumoniae infection. The tests included passive particle agglutination (PA) and enzyme-linked immunosorbent assay (ELISA). The seroprevalence rates of M. pneumoniae infection in the years 2004 and 2005 were 6.9 and 10.1%, respectively. The seropositivity rate was significantly higher in children (29.6% in 2005; 23.7% in 2004) than in adults (2.9% in 2005; 3.7% in 2004) (odds ratio, 8.138 in 2004; 13.923 in 2005; 95% confidence interval, 5.077-13.045 in 2004; 9.220-21.026 in 2005). Paired sera for the PA test were obtained from 32 of 399 children, and 22 of them demonstrated at least fourfold rises in antibody titer. ELISA had a sensitivity of 77.3% and a specificity of 40.0%; PA had a sensitivity of 9.5% and a specificity of 80%. The ELISA test was superior to the PA test in diagnosing acute M. pneumoniae infection in children. Both tests were significantly more sensitive when they were performed 1 week after the onset of infection. | 18,806,352 |
Case Study: Isolated Anterior lnterosseous Nerve Paralysis: The - Kiloh-Nevin Syndrome. | A new case of isolated paralysis of the anterior interosseous nerve of a 24-year-old man is described. It is thought that this was caused by a fall on the left arm. This paralysis has a typical clinical picture with a characteristic disturbance of the pinch grip. The patient recovered spontaneously. A review of the findings previously reported in the literature is presented. J Orthop Sports Phy Ther 1984;6(3):178-180. | 18,806,369 |
lsokinetic Evaluation of Tibial Rotation: Assessment of a Stabilization Technique*. | The purpose of this study was to present a wide range of normative data on maximum active tibial rotation utilizing isokinetic resistance and a relatively new stabilization technique. Both legs of 25 healthy adult male subjects were tested at 30, 60, 120, and 180 degrees per second of angular velocity. Data were collected on total range of motion, component internal/external range of motion (via two different methods), joint position at peak torque production, peak torque production, and torque production as a percentage of body weight. The effect of weight and leg length on peak torque production and total range of motion was also determined. In light of recent studies which have shown the need for specific rotational rehabilitation for rotatory knee instabilities, this study serves to present normative data for practical use in either the clinical or research setting. J Orthop Sports Phys Ther 1984;6(1):46-51. | 18,806,380 |
Pain complaint: comparison of electrical stimulation with conventional isometric exercise. | The purpose of this retrospective study was to assess the pain experiences of 17 healthy subjects who trained with isometric exercise, electrical stimulation, and the combination of isometric exercise and electrical stimulation. The McGill Pain Questionnaire was administered during posttest sessions upon termination of 5 weeks of training. Results indicated that subjects who received the electrical stimulation mode of training experienced similar torque gains but less muscle soreness than those who used conventional isometric exercise. Most subjects of the exercise and electrical stimulation groups experienced pain at the medial aspect of their knee, The pain was predominantly expressed as a sensory rather than an effective or an evaluative quality. Of all the trained subjects, those who received electrical stimulation described the greatest amount of transient discomfort. Electrical stimulation does not appear to increase the risk of discomfort more than volitional resistive exercise for achieving similar force-developing capacity of muscle in healthy subjects.J Orthop Sports Phys Ther 1984;5(6):318-323. | 18,806,388 |
The effect of physical activity on ligamentous strength: an overview*. | A brief review of the literature pertaining to the strengthening of ligamentous tissue through physical activity is presented. Although literature exists supporting both sides of the question, the predominence of evidence seems to be in favor of improved ligamentous strength following physical activity. Despite the general agreement, the exact mechanism involved is unclear. It is also unclear whether the ligament or the ligament-bone interface is the site of increased strength. A review of the possible mechanisms involved, as well as a discussion of the influence of immobility on the validity of the experimental results, is presented. J Orthop Sports Phys Ther 1984;5(5):275-277. | 18,806,403 |
Use of elbow dynasplint for reduction of elbow flexion contractures: a case study. | A severe elbow flexion contracture following a supracondylar fracture in a 13-yearold- male was treated with conventional physical therapy and an adjustable dynamic splint, the elbow Dynasplint(R). The Dynasplint was applied primarily at night. The patient achieved complete resolution of his flexion contracture. The Dynasplint incorporates the principles of adjustable, low-intensity force for prolonged durations of time.J Orthop Sports Phys Ther 1984;5(5):269-274. | 18,806,405 |
Norms for high school football players derived from cybex data reduction computer. | Three hundred and forty-two male high school football players, ranging in age from 15 to 17, were screened for muscular imbalances and joint abnormalities about the knee using a Cybex II lsokinetic Dynamometer and Cybex Data Reduction Computer. Each player was tested at speeds of 60, 240, 300 degrees , and 300" per second for muscular work. The athletes were classified by position (quarterback, runningback, tight end, wide receiver, linemen, linebacker, and defensive back). Several parameters were reported: peak torque with gravity effect for both extensors and flexors, peak torque to body weight, opposing muscle group ratios, torque acceleration energy, work over a preselected number of repetitions, endurance ratio, and agonist-antagonist work ratios. The purpose of the screening was to provide data beneficial for the prevention of injury from muscular imbalance and joint instability, data useful as clinical guidelines for rehabilitation and return to play, and suggestions for strength training programs. Previous articles have been published showing peak torque, and quadriceps and hamstring ratios, as a means of preventing injury due to muscular imbalance. However, until the introduction of the Cybex(R) Data Reduction Computer, authors had no way of taking the effect of gravity on the lower limb into consideration when presenting their findings. Hamstring-quadricep ratios, once thought to be ideal at 60% or better at 60 degrees per second are now better set at 50 to 55% with gravity effect at 60 per second. The intent of this paper is not to draw any specific conclusions but to present meaningful data for the purpose of preseason screening to prevent injuries and to aid in strength-training programs.J Orthop Sports Phys Ther 1984;5(5):243-245. | 18,806,406 |
Flexor hallucis longus tendinitis-a case of mistaken identity and posterior impingement syndrome in dancers: evaluation and management. | Flexor hallucis longus tendinitis and posterior impingement syndrome, two problems commonly encountered by dancers, but sometimes misdiagnosed, are presented and discussed in terms of anatomy, evaluation, and management.J Orthop Sports Phys Ther 1984;5(4):204-206. | 18,806,415 |
Survey of scholastic athletic health care and sports medicine clinics. | The increasing number of athletes requiring health care has spurred the growth of the development of sports medicine clinics. The diversity of such clinics is readily apparent. These clinics primarily function to provide evaluative and rehabilitative measures to all groups of athletic participants. Scholastic health care for athletic participants has not proceeded in a similar pattern. Sports medicine clinics are not effectively meeting the needs of the scholastic athlete, primarily because of location and financial limitations. This survey was conducted to collect information to further delineate the problems associated with scholastic health care of athletic participants. It appears that sports medicine clinics are manned by several levels of health care professionals. Scholastic athletes are least adequately covered by insurance and also suffer from being within a somewhat isolated environment. The need for on-field care and follow-up care within the school system remains a key problem associated with scholastic health care. Further research into the relationship of insurance policies which will adequately meet the needs of the scholastic population must be pursued. J Orthop Sports Phys Ther 1983;5(2):78-81. | 18,806,428 |
The definition and assessment of muscular power. | Considerable confusion still exists in the sports medicine literature concerning the measurement of muscular power and what it represents. Measures of muscular performance cannot be conveniently categorized as "strength " or ''power" on the basis of the contractile velocity employed in the performance task. Given the proper physical definitions and formulations involved in muscular power measurement, it is concluded that although strength (force output) and power (work/time) are quantitatively related, they remain separate physical parameters that can be measured in all dynamic muscular contractions, whether fast or slow. J Orthop Sports Phys Ther 1983;5(1):7-9. | 18,806,437 |
Spiradenoma and spiradenocylindroma with an adenomatous or atypical adenomatous component: a clinicopathological study of 6 cases. | We report 5 cases of spiradenoma and 1 case of spiradenocylindroma, which, in addition to areas of conventional growth, manifested an adenomatous component. This consisted of compactly situated, well-developed glands having small round lumens lined by inner pale to eosinophilic cells and surrounded by an outer well-formed peripheral layer of myoepithelial cells, which reacted with a variety of myoepithelial cell markers. In 1 case, apocrine secretion was evident in the glandular part of the lesion. In 4 of the 6 cases, the adenomatous component was a minor but significant portion of the tumors, but in 2 cases it was extensive, comprising approximately 20% of the tumor area. In 1 of these 2 cases, the luminal epithelium showed atypia including rare, atypical mitotic figures. In addition, there were foci of glands showing myoepithelial cell loss. As this alteration was limited and fairly well circumscribed within the tumor bulk, we regard it as an "atypical adenomatous component," but we cannot exclude the possibility that this may represent an incipient apocrine carcinoma, despite uneventful follow-up. Three cases also manifested clear cell areas. Immunohistochemical studies demonstrated that myoepithelial proliferation and overgrowth accounted for the clear cell change in some of the lesions. | 18,806,484 |
State of the art of teledermatopathology. | Teledermatopathology may involve real-time transmission of images from distant locations to consulting pathologists by the remote manipulation of a robotic microscope. Alternatively, the static store-and-forward option involves the single-file transmission of subjectively preselected and captured areas of microscopic images by a referring physician. The recent introduction of virtual slide systems (VSS) involves the digitization of whole slides at high resolution thus enabling the user to view any part of the specimen at any magnification. Such technology has surmounted previous restrictions caused by the size of preselected areas and specimen sampling for telepathology. In terms of client access, these VSS may be stored on a virtual slide server, made available on the Web for remote consultation by pathologists via an integrated virtual slide client network. Despite store-and-forward teledermatopathology being the most frequently used and less expensive approach to teledermatopathology, VSS represents the future in this discipline. The recent pilot studies suggest that the use of remote expert consultants in diagnostic dermatopathology can be integrated into daily routine, teleconsultation, and teleteaching. The new technology enables rapid and reproducible diagnoses, but despite its usability, VSS is not completely feasible for teledermatopathology of inflammatory skin diseases as the performance seems to be influenced by the availability of complete clinical data. Improvements in the diagnostic facility will no doubt follow from further development of the VSS, the slide processor, and of course training in the use of virtual microscope. Undoubtedly, as technology becomes even more sophisticated in the future, VSS will overcome the present drawbacks and find its place in all facets of teledermatopathology. | 18,806,486 |
Immunohistochemical investigation of mid-dermal elastolysis with a history of erythema. | Elastic fibers are essential extracellular matrix macromolecules comprising an elastin core surrounded by fibrillin-rich microfibrils. Fibulin-5, a microfibril, has been identified as one of the secreted extracellular matrix proteins that shows function as a scaffold for elastic fibers. However, the distribution of fibulin-5 in the skin is not clear. We report a case of a 43-year-old woman with erythema and subsequent wrinkling that met the clinical and histological criteria for mid-dermal elastolysis. We investigate the mechanism by which this disease occurs. The distribution of elastin, CD68, matrix metalloproteinase (MMP)-9, and fibulin-5 was examined immunohistochemically from both erythematous and wrinkled skin. There were numerous CD68 and MMP-9-producing histiocytes and giant cells in the erythematous lesions. Faint fibrillar staining of fibulin-5 was found in the deep dermis. In the wrinkled skin, there were few CD68 histiocytes or giant cells. Elastin immunoreactivity disappeared from the mid-dermis. Fibulin-5 colocalized in the lower dermis, shorter than in the erythema. Mid-dermal elastolysis may be initiated by MMP-9 produced by histiocytes and giant cells through its degradation of elastic fibers. In the lower dermis of the wrinkled skin, the fragmented expression of fibulin-5 was associated with the incomplete reproduction of the elastic fibers. | 18,806,493 |
Langerhans cell histiocytosis mimicking malignant melanoma: a diagnostic pitfall. | Langerhans cell histiocytosis (LCH), especially with an involvement limited to the skin, is a rare entity in adults. In formulating a differential diagnosis of a solitary skin lesion, LCH is rarely considered. Morphologically, cells seen in LCH can mimic those seen in a melanocytic tumor; moreover, they both show S-100 protein reactivity with immunoperoxidase staining. A 63-year-old male presented to a dermatology clinic with a solitary hyperpigmented macule on his right calf. A biopsy specimen showed epithelioid cells within the dermis, singly and in small groups, surrounded and infiltrated by collections of histiocytes and lymphocytes. These cells were diffusely positive for S-100 and negative for Melan-A. A diagnosis of malignant melanoma, spitzoid variant, was rendered, and the patient was sent to our melanoma center for surgical treatment. On histologic examination, some of the lesional cells had reniform, vesicular nuclei with central grooves. Additional immunoperoxidase staining showed strong, diffuse positivity for CD1a, supporting the diagnosis of LCH. LCH is morphologically similar to and can be misdiagnosed as malignant melanoma. It is important to be aware of this pitfall and utilize immunohistochemical and ultrastructural analysis to achieve correct diagnosis. | 18,806,499 |
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