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Polymorphisms of the leptin and HTR2C genes and clozapine-induced weight change and baseline BMI in patients with chronic schizophrenia.
We investigated the associations of the LEP-2548A/G and HTR2C-759C/T polymorphisms with long-term clozapine-induced weight changes and baseline BMI in chronic patients with schizophrenia. A total of 113 patients receiving clozapine for at least 1 year were enrolled. Body weight was measured cross-sectionally and data on body weight just before starting clozapine were retrospectively extracted from medical records. Clozapine-induced change in BMI was correlated inversely with the baseline BMI (P<0.001, ρ=-0.347). The LEP-2548A/G polymorphism was associated significantly with the change in BMI (F=4.380, P=0.015) during clozapine use; those with the AA genotype had the highest BMI gain (1.4±3.1 kg/m), followed by those with the AG (-0.2±3.3 kg/m) and GG (-1.6±3.4 kg/m) genotypes. We also found a significant association between the leptin genotype and BMI at baseline (F=3.499, P=0.034); those with the AA genotype had the lowest baseline BMI (23.4±4.3 kg/m), followed by those with the AG (24.1±4.4 kg/m) and GG (28.8±7.3 kg/m) genotypes. In the case of the HTR2C-759C/T polymorphism, we found a trend in which T alleles were more prevalent in male patients with up to 7% increase in BMI than in those with a greater than 7% increase in BMI [12/54 (22.7%) vs. 1/27 (3.7%); Fisher's exact test: P=0.051]. This study shows an inverse correlation between the baseline BMI and change in BMI during long-term clozapine use in patients with schizophrenia, and the LEP-2548A/G polymorphism was associated significantly with both these measures. | {
"pile_set_name": "PubMed Abstracts"
} |
Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) mRNA in normal and pathological adult human epididymis.
The pathogenesis of the aberrant development of the male genital tract (epididymis, vas deferens and seminal vesicles) seen in patients with congenital bilateral absence of the vas deferens (CBAVD) is still unclear. Since men with CBAVD carry mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), it is likely that CFTR mRNA of the translated protein plays a major role in the pathogenesis of CBAVD. The aim of this study was to compare the pattern of expression of CFTR mRNA in epididymides of men with CBAVD and other types of obstruction (post-vasectomy and post-inflammatory) with that of normal non-obstructed adult epididymis. Epididymal biopsies were obtained at the time of microsurgical epididymal sperm aspiration procedures or during vaso-epididymostomy reanastomosis. A normal epididymis was obtained from an orchiectomy specimen. After standard processing for in situ hybridization, tissue sections were hybridized with CFTR gene-probe labelled by incorporation of digoxigenin-dUTP. After hybridization the signal was detected by an alkaline phosphatase-tagged antidigoxigenin antibody. CFTR mRNA was clearly identified in the columnar epithelium of the normal adult epididymis and vas deferens and the signal intensity was greatest in the most proximal regions of the caput epididymis. In contrast, men with genital tract obstructions due to CBAVD or post-vasectomy or post-inflammatory obstructions, had sloughing of the epithelial cells lining the lumen and as a consequence CFTR mRNA expression was lacking. In one subject (post-vasectomy obstruction), some residual caput epididymal epithelium was preserved and CFTR mRNA was detected. The abundant CFTR mRNA expression in the proximal caput of the epididymis and vas deferens under normal conditions strongly favours the hypothesis of an early obstructive process in the pathogenesis of CBAVD. The absent or severely reduced activity of CFTR protein affects the ionic exchange and fluid content within the epididymal lumen and this, in turn, can lead to excessive viscosity of the epididymal fluid, sloughing of epithelial cells expressing CFTR and further reduction in the amount of CFTR activity. As a consequence, variable segments of the epididymis and the vas deferens may be blocked and progressively obliterated. The epididymal lumen obstruction could also sustain the anatomical defects by not allowing testosterone to exert a local action on the mesonephric duct. | {
"pile_set_name": "PubMed Abstracts"
} |
Sensitivity of photoreceptors to elevated levels of cGMP in the human retina.
When isolated human retinas were cultured in the presence of a phosphodiesterase inhibitor or dibutyryl cyclic guanosine monophosphate (dbcGMP), degenerative changes occurred which were proportional to the concentration of drug used and the period of exposure. Low concentrations of either drug did not alter retinal morphology as compared to controls. Higher concentrations provoked vesiculation of rod inner segments and rounding up of cones. Numerous pyknotic nuclei were noted in the outer nuclear layer of those preparations. Combining IBMX and dbcGMP in the same medium destroyed virtually every rod in the specimen within 8 hr of incubation. Under those conditions, cones remained structurally intact although somewhat rounded. In all treatments, cells of the innerretinal layers maintained normal morphology. Our results suggest that elevated levels of cGMP in the human retina can alter certain metabolic processes in photoreceptors, which leads to degenerative changes and cell death uniquely in rod photoreceptors. | {
"pile_set_name": "PubMed Abstracts"
} |
Psychrotrophic bacteria in sausage.
A total of 50 samples of frozen fresh beef sausage were collected from grocery stores at Beni Suef City. These samples were examined for enumeration, isolation and identification of psychrotrophic bacteria. All samples contained psychrotrophic bacteria in variable numbers. The mean counts of psychrotrophic bacteria, psychrotrophic Enterobacteriaceae, Pseudomonas, Aeromonas, Brochothrix thermosphacta and Lactic acid bacteria were 2 x 10(5) +/- 10(3), 6 x 10(3) +/- 4 x 10(2), 10(3) +/- 2 x 10(2), 4 x 10(2) +/- 8 x 10, 8 x 10(2) +/- 10(2) and 8 x 10(2) +/- 2 x 10(2) organisms per gram, respectively. Psychrotrophic Enterobacteriaceae isolates were identified biochemically. The hygienic significance of the isolates, their public health importance as well as supposed measures to improve the product are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Floating autostereoscopic 3D display with multidimensional images for telesurgical visualization.
We propose a combined floating autostereoscopic three-dimensional (3D) display approach for telesurgical visualization, which could reproduce live surgical scene in a realistic and intuitive manner. A polyhedron-shaped 3D display device is developed for spatially floating autostereoscopic 3D image. Integral videography (IV) technique is adopted to generate real-time 3D images. Combined two-dimensional (2D) and 3D displays are presented floatingly around the center of the display device through reflection of semitransparent mirrors. Intra-operative surgery information is fused and updated in the 3D display, so that telesurgical visualization could be enhanced remotely. The experimental results showed that our approach can achieve a combined floating autostereoscopic display that presents 2D and 3D fusion images. The glasses-free IV 3D display has full parallax and can be observed by multiple persons from surrounding areas at the same time. Furthermore, real-time surgical scene could be presented and updated in a realistic and intuitive visualization platform. It is shown that the proposed method is feasible for facilitating telesurgical visualization. The proposed floating autostereoscopic display device presents surgical information in an efficient form, so as to enhance operative cooperation and efficiency during operation. Combined presentation of imaging information is promising for medical applications. | {
"pile_set_name": "PubMed Abstracts"
} |
Exonic polymorphism vs intronic simple repeat hypervariability in MHC-DRB genes.
Gene products encoded by the major histocompatibility complex often exhibit a high degree of polymorphism. In humans the HLA-DR polymorphism is due to more than 50 alleles with varying exon 2 sequences. Each group of DRB alleles contains a certain form of the basic simple repeat motif (gt)n(ga)m in intron 2. Identical alleles can be differentiated on the basis of the hypervariable repeat. In this study focused on cattle (Bos taurus) we identified different Bota-DRB alleles in a limited survey by amplification via polymerase chain reaction and sequencing. In addition DRB exon 2 sequences were also obtained from eight additional hoofed animal species (seven horned artiodactyls and one pig) revealing artiodactyl-specific polymorphic and nonpolymorphic substitutions. In the genus Bos the intronic simple repeat variability was compared with exonic DRB polymorphism. As in humans all Bota-DRB exons were always associated with specifically organized basic simple repeat structures. Yet the extent of simple repeat variability was lower in cattle compared to humans. Selective breeding in the process of domestication might be responsible for the diminished intronic hypervariability. Nevertheless, the hypermutable simple repeat sequences have been preserved in the same position and with the same principal structure for at least 70 x 10(6) years of evolution. Unexpectedly, the rate of intronic simple repeat and exonic changes appear quite similar. | {
"pile_set_name": "PubMed Abstracts"
} |
Forearm SXA densitometry in 1,122 Polish women--a cohort study.
The aim of this study was to estimate forearm bone mineral density (BMD) and bone mineral content (BMC) using singleenergy X-ray absorptiometry (SXA) in a group of Polish women that included both pre- and post-menopausal subjects. The study was carried out in a cohort of 1,122 otherwise healthy women with no history of previous fractures. We showed a gradual decline of BMD and BMC with age, and the presence of suspected correlations of densitometric results with age and selected anthropometric parameters. Our study confirmed the utility of densitometric screening using forearm SXA measurements. These measurements discriminated clearly between pre- and post-menopausal subjects. Densitometric results correlated negatively with age and age at menopause, but positively with anthropometric indices related to body and skeletal size. Age was the greatest factor in terms of impact on bone loss. | {
"pile_set_name": "PubMed Abstracts"
} |
CT findings of pulmonary tuberculosis presenting as segmental consolidation.
The purpose of our study was to determine specific CT findings of tuberculous pneumonia presenting as segmental or lobar consolidation along with a pathologic review of specimens with similar radiographic patterns. CT findings of 45 cases of proven tuberculous pneumonia and 21 proven nontuberculous pneumonia were compared. Pathologic findings of five surgically resected tuberculous pneumonia cases were also investigated. The presence of fluid bronchogram (linear, branching shadow of fluid attenuation) and inner low attenuation/cavitation in the area of consolidation, luminal dilatation, and wall thickening of proximal bronchi were the main points sought on CT scan. In addition, the presence of bronchogenic dissemination, lymph node enlargement, and pleural lesions was also checked for in the unaffected area of both lungs. The following bronchial changes were seen in the tuberculous pneumonia and nontuberculous pneumonia groups, respectively: fluid bronchogram in 68.9 and 23.8% (p < 0.05), bronchial luminal dilatation in 60.0 and 23.8% (p < 0.05), and bronchial wall thickening of the proximal airway leading to the area of consolidation in 52.8 and 7% (p < 0.05). Bronchogenic dissemination outside the consolidation appeared in 88.9 and 52.4% (p < 0.05), respectively. In the tuberculous pneumonia group, lymph node enlargement and pleural reaction were seen in 55.6 and 35.6%, respectively, but in 42.9 and 57.1% in the nontuberculous pneumonia group (p > 0.05). Histologically, tuberculous pneumonia showed either bronchioles containing inflammatory exudates and submucosal granuloma or alveoli containing aggregates of alveolar macrophages or cellular debris. Fluid bronchogram in the area of homogeneous consolidation, bronchial luminal dilatation, and bronchial wall thickening of the proximal airway were the bronchial changes more significantly prominent in the tuberculous pneumonia group. We suspect that these findings may represent tuberculous bronchitis in small airways. | {
"pile_set_name": "PubMed Abstracts"
} |
LncRNA MEG3 inhibits the progression of prostate cancer by facilitating H3K27 trimethylation of EN2 through binding to EZH2.
This study aims to study the effects of intra-nuclear lncRNA MEG3 on the progression of prostate cancer and the underlying mechanisms. Expressions of relative molecules were detected by qRT-PCR and western blot. CHIP and RIP assays were used to evaluate the interaction between intra-nuclear MEG3, histone methyltransferase EZH2 and Engrailed-2 (EN2). The impacts of MEG3 on the viability, proliferation and invasion of prostate cancer cells (PC3) were evaluated by MTT, colony formation and transwell assays, respectively. PC3 cells were transfected with MEG3 and transplanted into nude mice to analyze the effect of MEG3 on tumorigenesis of PC3 cells in vivo. EN2 expression was inversely proportional to MEG3 in the prostate cancer tissues and PC3 cells. RIP results showed that intra-nuclear MEG3 could bind to EZH2. Knockdown of MEG3 and/or EZH2 up-regulated EN2 expression and reduced the recruitment of EZH2 and H3K27me3 to EN2, while over-expressed MEG3 caused opposite effects. MEG3 over-expression suppressed cell viability, colony formation, cell invasion and migration of PC3 cells in vitro and inhibited tumorigenesis of PC3 cells in vivo, while EN2 over-expression diminished the effects. These findings indicated that MEG3 facilitated H3K27 trimethylation of EN2 via binding to EZH2, thus suppressed the development of prostate cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
Pentoxifylline: its pharmacokinetics and ability to improve tumour perfusion and radiosensitivity in mice.
The pharmacokinetics of pentoxifylline and its three major metabolites were measured after intraperitoneal administration of 10 mg/g or 100 mg/kg of drug in C3H mice. Peak concentrations of pentoxifylline were approximately 10 and 100 micrograms/ml, respectively, with elimination half-lives (+/- 2 SE) of 4.6 (4.2-5.1) and 7.5 (7.2-7.9) min, respectively. Plasma concentrations of the pharmacologically active hydroxy metabolite were approximately one-tenth those of the parent compound. In vitro evidence of the ability of pentoxifylline to increase blood cell deformability indicates that concentrations of up to 30 micrograms/ml can increase deformability of both red and white blood cells; doses between 5 mg/kg and 100 mg/kg were therefore tested 15 min after administration to test the effect of the drug on tumour and normal tissue perfusion, tumour radiosensitivity and renal function immediately after exposure to appropriate drug concentrations. Using 86Rb extraction, doses of 10-100 mg/kg pentoxifylline were shown to increase relative tumour perfusion of the RIF-1 tumour to 140-170% of control, with no effect in skin, muscle, kidney, liver or lung, but with similar increases in spleen perfusion; there was no significant effect in any tissue after 5 mg/kg. Using a clonogenic assay, this increased tumour perfusion was shown to be reflected in increased tumour radiosensitivity to 25 Gy 15 min after pentoxifylline, with the same dose threshold of 10 mg/kg, and similar lack of dose-dependence at higher doses; the response indicated reduction in hypoxic fraction by a factor of 2-3. Renal function, measured by [51Cr]EDTA and [125I]iodohippurate clearance was unaffected at doses up to 50 mg/kg, with a slight effect at 100 mg/kg. The data indicate that pentoxifylline is effective at increasing relative tumour perfusion, with minimal effects on other tissues, and this increase is reflected in improved radiosensitivity. The doses at which the drug is effective are compatible with the mechanism being modification of blood cell deformability. Pentoxifylline shows promise as a clinical radiosensitiser acting by direct increase in tumour oxygenation. | {
"pile_set_name": "PubMed Abstracts"
} |
Longitudinal fMRI studies: Exploring brain plasticity and repair in MS.
Functional magnetic resonance imaging (fMRI) has greatly advanced our understanding of cerebral functional changes occurring in patients with multiple sclerosis (MS). However, most of our knowledge regarding brain plasticity and repair in MS as evidenced by fMRI has been extrapolated from cross-sectional studies across different phenotypes of the disease. This topical review provides an overview of this research, but also highlights limitations of existing fMRI studies with cross-sectional design. We then review the few existing longitudinal fMRI studies and discuss the feasibility and constraints of serial fMRI in individuals with MS. We further emphasize the potential to track fMRI changes in evolving disease and the insights this may give in terms of mechanisms of adaptation and repair, focusing on serial fMRI to monitor response to disease-modifying therapies or rehabilitation interventions. Finally, we offer recommendations for designing future research studies to overcome previous methodological shortcomings. | {
"pile_set_name": "PubMed Abstracts"
} |
Refractive index and spectral models for gradient-index materials.
Models are presented which describe the refractive index and spectral variation of gradient-index materials. Classes of gradient which exhibit little or no variation with wavelength are predicted. These are termed achromatic gradients. Experimental verification of the models is presented in a following paper. | {
"pile_set_name": "PubMed Abstracts"
} |
Measurement of HCV-Specific CD8(+) Cytotoxic T-Cell Activities in the Peripheral Blood by Europium Release Assay.
Peripheral blood mononuclear cells (PBMC) contain NK cells, cytotoxic T-lymphocytes (CTL), helper T-cells, and B-cells that respond to viral infection and act to eliminate the virus from infected individuals. CTLs are not only thought to be a major host defense against viral infection, but are also implicated in the immunopathogenesis. Classical CTLs are CD8(+) and recognize endogenously synthesized and processed antigen in association with a human leukocyte antigen (HLA) class I molecule. The antigens are usually 8-10 amino acids long. HCV-specific CTLs have been demonstrated in the peripheral blood of some of patients with HCV infection by stimulating PBMC with the HCV synthetic peptides (1). The peptides were synthesized as overlapping peptides to encompass a certain region of the HCV antigen (1), on the basis of antigenicity prediction from the amino acid composition of HCV (2), or on the basis of the HLA binding motifs in the HCV antigen (3). Several minimal and optimal epitopes in the HCV antigen and their HLA restriction of recognition by CTLs have been defined. Recently, it has been reported that HCV-specific CTLs may suppress the outgrowth of HCV (4). In this chapter, methods will be discussed that demonstrate HCV-specific CTLs in the peripheral blood of patients with HCV infection. We use nonradioisotope europium (Eu) for assay of CTL activities. | {
"pile_set_name": "PubMed Abstracts"
} |
Fathering Through Change (FTC) intervention for single fathers: Preventing coercive parenting and child problem behaviors.
Dishion and Patterson's work on the unique role of fathers in the coercive family process showed that fathers' coercion explained twice the variance of mothers' in predicting children's antisocial behavior and how treatment and prevention of coercion and promotion of prosocial parenting can mitigate children's problem behaviors. Using these ideas, we employed a sample of 426 divorced or separated fathers randomly assigned to Fathering Through Change (FTC), an interactive online behavioral parent training program or to a waitlist control. Participating fathers had been separated or divorced within the past 24 months with children ages 4 to 12 years. We tested an intent to treat (ITT) mediation hypothesis positing that intervention-induced changes in child problem behaviors would be mediated by changes in fathers' coercive parenting. We also tested complier average causal effects (CACE) models to estimate intervention effects, accounting for compliers and noncompliers in the treatment group and would-be compliers in the controls. Mediation was supported. ITT analyses showed the FTC obtained a small direct effect on father-reported pre-post changes in child adjustment problems (d = .20), a medium effect on pre-post changes in fathers' coercive parenting (d = .61), and a moderate indirect effect to changes in child adjustment (d = .30). Larger effects were observed in CACE analyses. | {
"pile_set_name": "PubMed Abstracts"
} |
Interannual variability of soft-bottom macrobenthic communities of the NW Gulf of Mexico in relationship to the Deepwater Horizon oil spill.
A 3-year research program was undertaken to assess potential environmental disturbance caused by the Deepwater Horizon oil spill to the soft-bottom macrobenthic communities within Mexican waters of the northwestern Gulf of Mexico. Community properties and temporal/spatial variability were analyzed besides toxicant parameters such as hydrocarbons and trace-metals. Overall infaunal density increased, taxa proportion changed, and small-size opportunistic organisms prevailed throughout the study. Annual abundance-biomass comparison (ABC) curves revealed progressive stress scenarios from moderate to severe. Concentrations of vanadium, nickel, cobalt, PAHs and AHs increased gradually over time. However, low correlations between benthic density and biogeochemical variables were determined. Initially, sedimentary properties were the main drivers of benthic community structure; subsequently, nickel, vanadium and PAHs, indicative of anthropogenic effect, were highlighted. Interannual variability in the macroinfauna was attributed to the synergy of several environmental factors. Undoubtedly, compounds derived from fossil fuels had a significant disturbance role, but their source remains uncertain. | {
"pile_set_name": "PubMed Abstracts"
} |
Irreversible dimerization/tetramerization and post-translational modifications inhibit proteolytic degradation of A beta peptides of Alzheimer's disease.
Experimental evidence increasingly implicates the beta-amyloid peptide in the pathogenesis of Alzheimer's disease. Beta-amyloid filaments dramatically accumulate in the neuritic plaques and vascular deposits as the result of the brain's inability to clear these structures. In this paper, we demonstrate that in addition to the intrinsic stability of A beta N-42, the time dependent generation of irreversibly associated A beta dimers and tetramers incorporated into A beta filaments are themselves resistant to proteolytic degradation. The presence of post-translational modifications such as isomerization of aspartyls 1 and 7, cyclization of glutamyl 3 to pyroglutamyl and oxidation of methionyl 35, further contribute to the insolubility and stability of A beta. All these factors promote the accumulation of neurotoxic amyloid in the brains of patients with Alzheimer's disease, and should be considered in therapeutic strategies directed towards the dissociation of the brain's A beta filaments. | {
"pile_set_name": "PubMed Abstracts"
} |
Corticotropin-releasing factor (CRF): stimulation in normal controls and in patients with Cushing's syndrome.
Synthetic ovine and human CRF were given as an i.v. bolus to six healthy volunteers in four and two different dosages, respectively (oCRF: 25, 50, 100 and 200 micrograms; hCRF: 50 and 100 micrograms). There was a significant increase of ACTH and cortisol after the injection of all dosages though the dose-response relationship was only significant between the 50 and 100 micrograms dose of oCRF. No significant differences between ACTH and cortisol secretion after oCRF and hCRF were observed. Repetitive stimulation by hCRF led to repetitive release of identical amounts of ACTH. The CRF test with the 100 micrograms dosage was used in patients with proven Cushing's syndrome (n = 30). Results showed that the CRF test is useful in making the differential diagnosis of established Cushing's syndrome. In patients with ACTH-dependent Cushing's disease (n = 21), normal or elevated basal ACTH levels were significantly higher after stimulation by CRF compared to normal controls, with one exception. The pattern of cortisol secretion after CRF administration corresponded to the pattern of ACTH secretion in these patients. In two patients with ectopic ACTH syndrome, extremely elevated ACTH and cortisol levels did not change or showed only a small increase after CRF administration. In patients with unilateral adrenal adenoma or carcinoma (n = 7), suppressed ACTH levels did not rise after CRF administration. In addition, no significant change in cortisol secretion could be observed. After surgical removal of cortisol-producing adrenal tumors, the ACTH response to CRF can be demonstrated when cortisol levels are still undetectable. Pulsatile administration of CRF in one patient after unilateral adrenalectomy revealed that ACTH responses to CRF normalize rapidly but cannot be sustained if CRF administration is withdrawn, suggesting that the cause of adrenal failure after unilateral adrenalectomy for Cushing's syndrome or with long-term corticoid therapy is due to hypothalamic CRF deficiency. The suppression of ACTH responses to CRF in glucocorticoid-treated patients correlated with the daily corticoid dosage. Since the ACTH hyper-response to CRF in six patients with Cushing's disease was suppressed by short-term dexamethasone treatment, the pituitary as a target site for feedback inhibition also was demonstrated. | {
"pile_set_name": "PubMed Abstracts"
} |
Transcriptome of axenic liver stages of Plasmodium yoelii.
Plasmodium liver stages or early exo-eythrocytic forms (EEFs) contain antigens that are essential for achieving sterile, protective immunity against malaria. Yet, attempts at identifying these antigens have been hampered by the challenge of obtaining large numbers of purified EEFs, uncontaminated with hepatocyte material. Using a recently described system for producing axenically cultured EEFs from Plasmodium yoelii, we have constructed a cDNA library and generated 1453 expressed sequence tags (ESTs) resulting in 652 unique transcripts. Analysis of the library provides insight into processes required for the initiation and development of Plasmodium liver stages, such as protein degradation, cell cycle progression and nutrient transport. Analysis of the gene expression profile of liver stages, as revealed by this library, suggests that liver stages represent a shift from "sporozoite-like" to "blood-stage-like". This is the first study of the transcriptional repertoire of Plasmodium liver stages. | {
"pile_set_name": "PubMed Abstracts"
} |
A study of xanthopterin in chronic renal failure.
Xanthopterin, a metabolic end product of the nonconjugated pterins dihydrobiopterin and tetrahydrobiopterin, is present in many organs and is known to inhibit the proliferation and growth of conconavalin-stimulated lymphocytes. We have developed a simple fluorometric method to measure xanthopterin in the blood and have validated the method by high pressure liquid chromatography (HPLC). Serum levels were 14 +/- 7 nmol/l in normal subjects and 141 +/- 51 nmol/l in hemodialysis patients (p < 0.02). Intermediate levels from patients with renal insufficiency not on dialysis correlated with serum creatinine levels (p < 0.001). Xanthopterin (MW 179) was cleared by hemodialysis at a slightly lower rate than creatinine. It is bound to protein, but the binding, 90 +/- 5% in normal subjects, is decreased in uremia to 60 +/- 15%, p < 0.01. Red cell levels of xanthopterin were five times higher than those of plasma in normal subjects (69 +/- 15 vs. 14 +/- 7 nmol/l, p < 0.001), but uremic patients had lower levels in red cells than in plasma (101 +/- 24 vs. 141 +/- 51 nmol/l, p < 0.05). Slight or moderate hemolysis induced by mechanical stress increased plasma xanthopterin levels by 35%, the effect being more pronounced when hemolysis was severe. We conclude that xanthopterin is increased and its binding to protein is decreased in chronic renal failure. The altered ratio of red cell/plasma xanthopterin levels may reflect an abnormality of the red cell membrane in uremia. We are conducting further studies to amplify our preliminary findings that xanthopterin inhibits cellular growth in vitro. | {
"pile_set_name": "PubMed Abstracts"
} |
Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study.
Bone-marrow micrometastases have been found in patients with primary breast cancer. We report long-term follow-up of women with primary breast cancer, diagnosed between 1981 and 1986, who had multiple aspirates taken at the time of initial surgery. 350 women with primary breast cancer were examined immunocytochemically with antibody to epithelial membrane antigen. We investigated associations with various prognostic factors as well as the effect of micrometastases on relapse-free survival and overall survival. At median follow-up of 12.5 years, 151 patients had metastatic disease and 136 patients had died from breast cancer. 10-year relapse-free and overall survival were 43.9% (95% CI 33.4-54.7) and 44.9% (34.2-55.9) in patients with micrometastases, and 62.7% (56.5-68.6) and 65.7% (59.4-71.5) in patients without micrometastases at presentation (p<0.001). For relapse-free survival and overall survival, allowing for tumour size, lymph-node status, and vascular invasion, the effect of micrometastases decreased and was no longer significant, with a hazard ratio of 1.09 (0.74-1.61) for relapse-free survival and 1.21 (0.84-1.75) for overall survival. The presence of bone-marrow micrometastases in patients with primary breast cancer is associated with a shorter relapse-free survival and overall survival, but is not an independent prognostic factor. This immunocytochemical technique may be of value in patients for whom pathological tumour size and lymph-node status are unavailable (ie, patients receiving primary medical treatment). | {
"pile_set_name": "PubMed Abstracts"
} |
Staged abdominal repair in the treatment of intra-abdominal infection: analysis of 102 patients.
Surgical treatment of intra-abdominal infections remains a challenge for the surgeon. Staged abdominal repair is being commonly used in patients with intra-abdominal infections. This study presents our experience with staged abdominal repair and analyzes factors affecting mortality. A total of 102 patients who underwent staged abdominal repair procedures for intra-abdominal infections during a 12-year period were retrospectively reviewed. The effects of several risk factors on mortality were evaluated. The investigated risk factors included age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, number of operations prior to staged abdominal repair, number of repeat laparotomies, anatomic origin of infection, and etiology of intra-abdominal infections. The overall mortality rate was 40% (41/102). The mean number of operations prior to staged abdominal repair (0.72 +/- 0.1 in survivors vs. 1.37 +/- 0.21 in nonsurvivors), age (24.5% mortality under 55 years vs. 53.6% mortality between 55 and 65 years vs. 75% mortality over 65 years), and APACHE II score (13.4 +/- 3.4 in survivors vs. 20.3 +/- 6.64 in nonsurvivors) were correlated with mortality rates (P < 0.05). Our results showed that the physiologic status of patients, severity of sepsis, and decision time for staged abdominal repair were all associated with higher mortality. | {
"pile_set_name": "PubMed Abstracts"
} |
[The flu syndrome: update and therapeutic and prophylactic approach].
Authors in the present work analyse the history of the flu from V century A.C. until our days. We can know the different flu epidemic the structure of the virus and to take note of the different preventing device; of these the core is the vaccine. Thanks the vaccine is possible to weaken the big epidemics. Authors attract the importance on the mass vaccine and conclude to mention the new antivirus drugs per os. | {
"pile_set_name": "PubMed Abstracts"
} |
Anti-inflammatory and antinociceptive activity of flavonoids isolated from Viscum album ssp. album.
Viscum album L. has been used in the indigenous systems of medicine for treatment of headache and some inflammatory diseases. In order to evaluate this information, antinociceptive and anti-inflammatory activities of the five flavonoids (5,7-dimethoxy naringenin or 4',6'-dimethoxy chalcononaringenin) derivatives, isolated from the ethyl acetate fraction of the extract from V. album ssp. album, were investigated, namely 5,7-dimethoxy-flavanone-4'-O-beta-D-glucopyranoside (1), 2'-hydroxy-4',6'-dimethoxy-chalcone-4-O-beta-D-glucopyranoside (2), 5,7-dimethoxy-flavanone-4'-O-[2"-O-(5"'-O-trans-cinnamoyl)-beta-D-apiofuranosyl]-beta-D-glucopyranoside (3), 2'-hydroxy-4',6'-dimethoxy-chalcone-4-O-[2"-O-(5"'-O-trans-cinnamoyl)-beta-Dapiofuranosyl]-beta-D-glucopyranoside (4), 5,7-dimethoxy-flavanone-4'-O-[beta-D-apiofuranosyl-(1 --> 2)]-beta-D-glucopyranoside (5). For the antinociceptive activity assessment the p-benzoquinone-induced writhing test and for the anti-inflammatory activity the carrageenan-induced hind paw edema model in mice were used. The ethyl acetate fraction in a dose of 250 mg/kg as well as compounds 2 and 5 in a 30 mg/kg dose were shown to possess remarkable antinociceptive and anti-inflammatory activities per os without inducing any apparent acute toxicity as well as gastric damage. | {
"pile_set_name": "PubMed Abstracts"
} |
[Repeated cold water stimulations (hydrotherapy according to Kneipp) in patients with COPD].
Patients with chronic obstructive pulmonary disease (COPD) often suffer from exacerbations caused by infections of the bronchial tract. What effects do hydrotherapeutic applications according to Kneipp have on lung function, blood gases, immune system and quality of life of patients with COPD? 20 patients with COPD (17 males, 3 females); mean age: 64; forced expiratory volume (FEV1): 62 of 100% (on average); no acute exacerbations, no oral corticosteroids. Measurements were performed (I) at 10 weeks pre-treatment, (II) immediately before therapy (I-II: baseline-period), (III) after 10 weeks treatment with 3 cold affusions and 2 cold washings of the upper part of the body (self-treatment) per week each, (IV) 3 months after completion of the treatment (follow- up). The following parameters were measured: lung function, blood gases, routine lab, experimental lab (interleukines, lymphocytes), maximal expiratory flow (PEF), quality of life and respiratory infections. The pH increased over the course of the study. PEF and the number of lymphocytes significantly increased over the treatment (II-III). Intracellular expression of IL-4 by T lymphocytes decreased. However, the expression of IFN-gamma increased. Frequency of infections was lower during follow-up (IV) than before and during therapy. Quality of life after treatment was estimated to be good in all patients. Repeated cold stimulations (affusions) can influence the frequency of respiratory infections and improve subjective well-being. It may cause an immunological modulation in terms of the Th1-type pattern. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors associated with breast self-examination among Malaysian women teachers.
The purpose of this study was to examine factors related to breast self-examination (BSE) among teachers in Selangor, Malaysia. A cross-sectional study was conducted among 425 female teachers in 20 randomly selected secondary schools. A self-administered questionnaire based on the health belief model was randomly selected secondary schools. A self-administered questionnaire based on the health belief model was used, including sociodemographic background and knowledge, beliefs and practices about breast cancer and BSE. Only 19% of the women performed BSE on a regular basis. Higher knowledge about breast cancer, greater confidence in performing BSE and regular visits to a physician were significant predictors for practising BSE. To promote BSE practice among Malaysian women, tailored health education and health promotion programmes should be developed based on a specific understanding of women's health beliefs. | {
"pile_set_name": "PubMed Abstracts"
} |
Prediction of UGIB event in NSAID users: a model development.
The purpose of this study was to create a predicting tool for UGIB event in NSAID users. The patients of this case-control study were NSAID users who had received NSAIDs for at least 3 days and were gastroscoped The patients with a history of gastrointestinal varices, gastrointestinal cancer, chronic renal failure, coagulopathy, or Mallory-Weiss tear were excluded. The data was collected between July 2001 and January 2002 by patient interviewing and medical record reviewing. One hundred and fifty four NSAID users were identified (89 in the UGIB group, 65 in the non-bleeding group). Most patients were elderly (mean age +/- SD: 60.9 +/- 12.6 years). Age and the number of current NSAID users were significantly higher in UGIB patients than in non-bleeding patients (p < 0.05 and p < 0.01, respectively). The number of antiulceration drug users in non-bleeding patients was higher than in UGIB patients (p < 0. 01). An equation for prediction of UGIB probability in NSAID users was generated by using enter logistic regression. The best model of predicting the risk of UGIB event in NSAID users was logit (UGIB) = 0.33 + 2.09 Multiple NSAID use + 1.43 H. pylori infection + 0.34 Current NSAID use + 0.12 (Age x Sex) - 8.53 Sex - 2.41 Antiulceration drugs - 0. 000048 Age. The model had 80.2% of the overall rate of correct classification. The positive and negative predictive values were 80.8% and 78.9% respectively. The probability of UGIB = e((logit(UGIB)) /1 + e(logit(UGlB)). If the value of the probability of UGIB is more than 0. 5, the patient has a high risk of UGIB. Multiple NSAID use is the strongest factor that affects the probability of UGIB in NSAID users. H. pylori infection is another strong risk factor of NSAID-related UGIB. Antiulceration drug usage reduced the risk of UGIB in this group of patients. The developed model can be used as a guide for pharmacotherapeutic planning in clinical practices. | {
"pile_set_name": "PubMed Abstracts"
} |
Incidence and characterization of serum transaminases elevations in pegylated interferon and ribavirin treated patients with chronic hepatitis C.
A virological response to pegylated-interferon and ribavirin is typically associated with a prompt fall in serum transaminases. For some patients, transaminases rise during treatment. To assess the frequency and define factors associated with elevations of serum transaminases. A total of 169 treated patients were studied. Transaminase elevations were graded by WHO criteria - grade 0: no value > baseline, grade 1: 1-2x baseline, grade 2: 2.1-5x baseline, grade 3: >5x, grade 4: any rise with evidence of liver failure. Results 60/169 (35%) patients experienced transaminase elevations: 52 grade 1, 6 grade 2, 1 grade 3, 1 grade 4. Overall, end of treatment response and sustained virological response rates were 72% and 55%. Lower rates were observed in the grade 1 elevation group (63% and 40%) compared with patients with grade 0 (79% and 65%) and grade > or =2 elevations (85% and 71%). Grade 1 elevations tended to occur earlier during treatment than grade > or =2 elevations. Transaminase elevations were associated with greater pre-treatment body weight (P = 0.006), steatosis (P = 0.008) and poorer sustained virological response rates (P = 0.007). Transaminase elevations during treatment of chronic Hepatitis C virus with pegylated interferon and ribavirin are common but rarely severe. Mild rises may reflect ongoing viral activity in treatment non-responders. More significant rises are frequently observed despite a virological response, and may be because of an immuno-modulating effect of interferon in susceptible patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Modulation by alpha- and gamma-tocopherol and oxidized low-density lipoprotein of apoptotic signaling in human coronary smooth muscle cells.
Apoptosis may play an important role in atherogenesis. Oxidized low-density lipoprotein (oxLDL) promotes apoptosis in the arterial wall in addition to several other proatherogenic effects. Tocopherol supplements have been suggested to protect against coronary heart disease (CHD) in epidemiological studies. The effects of oxLDL and alpha- and gamma-tocopherol on apoptotic signaling pathways are poorly understood. Thus, the goal of the study was to investigate these pathways in the presence of copper-oxidized LDL and tocopherols in human coronary smooth muscle cells (SMC). We showed that oxLDL-mediated apoptosis, assessed by DNA fragmentation, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, and caspase activation stimulated several transcription factors and proapoptotic dynamic movements of the Bcl-2 family proteins through the mitogen-activated protein kinase (MAPK) and Jun kinase pathways. alpha-Tocopherol and gamma-tocopherol significantly reduced these molecular events and cell death effectors caspase-3 and -8. Under our experimental conditions, alpha-tocopherol was significantly more effective than gamma-tocopherol, and oxLDL-mediated apoptosis increased c-Jun, cyclic AMP-responsive element-binding, Ets-like element kinase-dependent 7, and activating transcription factor-2 proteins as well as nuclear activity of the activated protein-1 complex in human coronary SMC. Moreover, our results demonstrate that tocopherols may exert their antiatherogenic effects at least in part via reduction of the MAPK and JunK cascade together with a protective profile of apoptotic genes of the Bcl-2 family. These data are consistent with the beneficial effects of tocopherols on atherogenesis seen in experimental studies and on CHD in epidemiological surveys. | {
"pile_set_name": "PubMed Abstracts"
} |
Familial primary carpal tunnel syndrome with possible skipped generation.
Carpal tunnel syndrome, an entrapment neuropathy of the median nerve, is rarely seen in childhood. Familial carpal tunnel syndrome, an even more exceptional entity, is frequently associated with inherited systemic disorders. Rarely it can be presented as a primary familial form with Mendelian autosomal dominant inheritance. We report the occurrence of carpal tunnel syndrome in two generations of a family in which the index case was a 6-year-old boy with bilateral hand pain and paresthesias. Our report demonstrates an interesting inheritance pattern of carpal tunnel syndrome in a family transmitted by an autosomal dominant gene with variable expressivity and reduced penetrance. To our knowledge, it is the first report of familial bilateral carpal tunnel syndrome in a family with possible skipped generation. | {
"pile_set_name": "PubMed Abstracts"
} |
[RAS mutations at the molecular tumor conference].
Members of the rat sarcoma (RAS) gene family belong to the most frequently mutated genes that drive pathogenesis and therapy response. As the discovery of their malignant potential dates back more than three decades, cellular mutated RAS genes and their products belong to the best characterized cancer genes. Despite urgent clinical needs, RAS therapies are still elusive and limited to preclinical studies. However, very recently, novel and promising approaches have become a reality in clinical applications and trials. In the near future, interesting therapeutic options will emerge that are capable of targeting "undruggable" RAS. This will be even more important as the detection of RAS mutations has already been an integral part of routine molecular diagnostics for many years. | {
"pile_set_name": "PubMed Abstracts"
} |
The use of initiated cells as a test system for the detection of inhibitors of gap junctional intercellular communication.
The effects of five non-mutagenic carcinogens--Aroclor 1260, benzoyl peroxide (BP), phenobarbital (PB), 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 1,1'-(2,2,2-trichloroethylidene)bis[4-chlorobenzene] (DDT)--on gap junctional intercellular communication (GJIC) were tested in a cell line consisting of initiated cells (3PC). Four agents suspected of tumor promotion activity--o-anisidine, clofibrate, L-ethionone and d-limonene--were also tested for their effects on GJIC. Finally sodium fluoride (NaF), whose carcinogenic property is still unclear, was tested for its effects on GJIC in the 3PC cell line. Four of the five selected tumor promoters (Aroclor 1260, BP, DDT and TPA) decreased GJIC between these initiated epidermal cells. The four non-mutagenic carcinogens with tumor-promoting activity in vivo (o-anisidine, clofibrate, L-ethionine and d-limonene) all inhibited GJIC, whereas NaF had no effect. Seven compounds (o-anisidine, Aroclor 1260, BP, DDT, L-ethionine, d-limonene and TPA) had a dose-dependent as well as time-dependent inhibitory effect on GJIC. Under the experimental conditions used, clofibrate showed only a dose-related inhibition of GJIC. PB showed no inhibitory effect on GJIC in the 3PC cell line. In order to determine the role of biotransformation in the tumor-promoting activity of PB, its effect on GJIC was also examined in the presence of an Aroclor 1254-induced rat liver homogenate (S9 mix) and in the hepatoma cell line HepG2. In the presence of rat liver homogenate PB decreased GJIC in the 3PC cell line, whereas in the HepG2 cells PB showed a time- and dose-dependent inhibitory effect. To study the potential differences in susceptibility of cells representing different stages in the process of tumor formation, the effect of the selected tumor promoters on GJIC was also investigated in primary mouse keratinocytes and in a mouse skin carcinoma-derived cell line (CA3/7). Primary keratinocytes were sometimes more (BP and clofibrate) and sometimes less sensitive (ethionine and limonene) for inhibitory effects on GJIC compared to the effects in the cell line 3PC. Except for TPA and anisidin, GJIC between the CA3/7 cells was less affected by the selected agents compared to the 3PC cell line. These results show that, during the process of tumor formation the susceptibility of cells to inhibition of GJIC by tumor promoters is variable. Overall the CA3/7 cells are less sensitive compared to 3PC cells. The susceptibility of primary keratinocytes is variable compared to 3PC cells, depending on the agent used. These results also show that GJIC is a valid parameter for testing the tumor-promoting activity of compounds. Finally, this study demonstrates that mouse keratinocyte cell lines could serve as an in vitro model for the detection of non-mutagenic carcinogens with diverse target organs in vivo. For this use the cell line consisting of initiated cells (3PC) is more sensitive than the carcinoma-derived cell line CA3/7. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of a lactoperoxidase-thiocyanate-hydrogen peroxide system on Salmonella enteritidis in animal or vegetable foods.
Lactoperoxidase (LPO) from skim milk was purified by ion-exchange chromatography. The purified protein was used to catalyze the oxidation of thiocyanate by H2O2 in an antibacterial system (LPO system). The LPO system was used to inactivate or inhibit Salmonella enteritidis in tomato juice, carrot juice, milk, liquid whole egg, and chicken skin extract under various conditions. The system was found to be more effective against the organism in vegetable juices than in animal products, at low pH than at neutral pH, and at higher temperatures than at lower temperatures. Acid-adapted S. enteritidis cells were more susceptible than nonadapted cells. The system reduced numbers of S. enteritidis in vegetable products by up to 5.4 log units and inhibited growth of the organism in animal-derived foods during 4 h incubation at 30 degrees C. Sodium chloride (>100 mM) and polyphosphate (0.01-0.5%) enhanced the antibacterial effects of the system in tomato juice and chicken skin extract, respectively. The findings indicate that the LPO system could probably be used to prevent the growth and survival of salmonellae in minimally processed fruit and vegetable products, but combination of the system with other preservatives or treatments would be needed to effectively inhibit growth and survival of salmonellae in animal products. | {
"pile_set_name": "PubMed Abstracts"
} |
[Effects of human atrial natriuretic factor-(99-126) on plasma and brain vasopressin in stroke-prone spontaneously hypertensive rats].
In order to investigate the interaction between atrial natriuretic factor (ANF) and arginine vasopressin (AVP) in the pathogenesis of essential hypertension, the effects of intravenous (iv) or intracerebroventricular (icv) injection of human ANF-(99-126) on plasma and brain AVP, as well as mean arterial pressure (MAP), urinary volume (UV) and sodium (UNaV) excretion in stroke-prone spontaneously hypertensive rats (SHRsp) and age-matched normotensive Wistar-Kyoto rats (WKY) were studied. The results showed that ten minutes after iv injection of ANF, MAP decreased by 9.4% and 12.2% (P less than 0.05), UV increased about 9 and 20 folds (P less than 0.01), UNaV increased about 16 and 29 folds (P less than 0.01) in SHRsp and WKY rats, respectively. No such significant changes in these parameters were found in the icv group. Although iv and icv injection of ANF caused significant decrease of plasma AVP in both strains, the decrease was less marked in SHRsp than in WKY rats, while the maximum decreases were 58% (iv) and 31% (icv) in SHRsp, the corresponding values were 80% (iv) and 65% (icv) in WKY. Intravenous and intracerebroventricular injection of ANF also induced significant increase of hypothalamic AVP in both SHRsp and WKY rats, but no significant change could be found in hypophyseal AVP content. The results suggest that decreased sensitivity of AVP inhibition as well as less marked hypotensive, diuretic and natriuretic effects to ANF in SHRsp might play a role in the pathogenesis of their hypertension. | {
"pile_set_name": "PubMed Abstracts"
} |
A Positive Youth Development Approach to Improving Mental Health Outcomes for Maltreated Children in Foster Care: Replication and Extension of an RCT of the Fostering Healthy Futures Program.
Preventing the negative impact of maltreatment on children's mental health requires interventions to be contextually sensitive, grounded in theory and research, and effective in reaching and retaining children and families. This study replicates and extends previous findings of the Fostering Healthy Futures (FHF) program, a 30-week mentoring and skills group intervention for preadolescent maltreated children in foster care. Participants included 426 children recently placed in out-of-home care who were randomized to intervention or control conditions. Outcomes measured 6-10 months postintervention included a multi-informant (child, caregiver, teacher) index of mental health problems as well as measures of posttraumatic stress symptoms, dissociative symptoms, quality of life, and use of mental health services and psychotropic medications. There were high rates of program initiation, retention, and engagement; 95% of those randomized to FHF started the program, 92% completed it, and over 85% of the mentoring visits and skills groups were attended. The FHF program demonstrated significant impact in reducing mental health symptomatology, especially trauma symptoms, and mental health service utilization. These program effects were consistent across almost all subgroups, suggesting that FHF confers benefit for diverse children. Results indicate that positive youth development programming is highly acceptable to children and families and that it can positively impact trauma and its sequelae. | {
"pile_set_name": "PubMed Abstracts"
} |
Nonsustained ventricular tachycardia in coronary artery disease: relation to inducible sustained ventricular tachycardia. MUSTT Investigators.
Many physicians believe that electrocardiographic characteristics of nonsustained ventricular tachycardia correlate with the risk for sudden death in survivors of myocardial infarction. Sustained ventricular tachycardia induced by programmed electrical stimulation has also been shown to predict sudden death. To determine whether electrocardiographic characteristics of spontaneous nonsustained ventricular tachycardia can predict the inducibility of sustained ventricular tachycardia by programmed electrical stimulation in patients with coronary artery disease having abnormal ventricular function. Observational cohort study. 70 clinical electrophysiology laboratories in the United States and Canada. 1480 consecutive patients with coronary artery disease, left ventricular ejection fraction of 0.40 or less, and asymptomatic nonsustained ventricular tachycardia. Electrophysiologic study attempting to induce sustained monomorphic ventricular tachycardia. Daily frequency, duration, and cycle length of spontaneous episodes of nonsustained ventricular tachycardia, measured by standard electrocardiographic recordings. No statistically significant difference in the frequency or duration of spontaneous nonsustained ventricular tachycardia was seen between patients with and those without inducible sustained ventricular tachycardia. Rates of spontaneous tachycardia were slightly slower in patients with inducible ventricular tachycardia than in patients without inducible ventricular tachycardia (P = 0.047), but the difference was not clinically significant. Electrocardiographic characteristics of spontaneous nonsustained ventricular tachycardia do not predict which patients with coronary artery disease will have inducible sustained ventricular tachycardia. | {
"pile_set_name": "PubMed Abstracts"
} |
[Influence of biomass burning in Central Asia on nitrate concentrations in Urumqi Glacier No. 1, eastern Tianshan Mountains, China].
Influence of biomass burning in Kazakhstan on nitrate concentrations in eastern Tianshan Mountains was studied. 52 samples of surface snow and snow pits were collected from Glacier No. 1 at the headwater of Urumqi River in eastern Tianshan Mountains, China. Nitrate concentrations in these samples were measured and atmospheric transmission was reconstructed with HYSPLIT air trajectory model. The objectives of this study were to identify the relationship between steppes fire and nitrate concentration in snow, and develop deposition process of nitrate caused by biomass burning in alpine glacier at high altitude. Results indicated that nitrate in surface snow could be regarded as a subsidiary indicator of biomass burning for long distance. Correlations for NO3- and K+ were 0.74 from mid September to late October 2002, which was obviously higher than mean concentration. It took 2-6 days from fire spots in Kazakhstan to sampling site. Whether the information in air mass with biomass burning products can be recorded or not, was mostly depend on local temperature and precipitation. Eluviation process was prominent at Glacier No. 1 in wet season, so postdepositional effect should be considered in paleoclimate reconstruction by ice core. | {
"pile_set_name": "PubMed Abstracts"
} |
Rome IV. Gallbladder and Sphincter of Oddi Disorders.
The concept that motor disorders of the gallbladder, cystic duct and sphincter of Oddi can cause painful syndromes is attractive and popular, at least in the USA. However, the results of commonly performed ablative treatments (cholecystectomy and sphincterotomy) are not uniformly good. The predictive value of tests that are often used to diagnose dysfunction (dynamic gallbladder scintigraphy and sphincter manometry) is controversial. Evaluation and management of these patients is made difficult by the fluctuating symptoms and the placebo effect of invasive interventions. A recent stringent study has shown that sphincterotomy is no better than sham treatment in patients with post-cholecystectomy pain and little or no objective abnormalities on investigation, so that the old concept of sphincter of Oddi dysfunction (SOD) type III is discarded. ERCP approaches are no longer appropriate in that context. There is a pressing need for similar prospective studies to provide better guidance for clinicians dealing with these patients. We need to clarify the indications for cholecystectomy in patients with Functional Gallbladder Disorder (FGBD) and the relevance of sphincter dysfunction in patients with some evidence for biliary obstruction (previously SOD type II, now called "Functional Biliary Sphincter Disorder - FBSD") and with idiopathic acute recurrent pancreatitis. | {
"pile_set_name": "PubMed Abstracts"
} |
Kinetics of large ciliate protozoa in the rumen of cattle given sugar cane diets.
1. Experiments were undertaken to examine the kinetics of large ciliate protozoa in the rumen of cattle on sugar-cane diets. 2. Three Zebu bulls were fed once daily on a diet of sugar cane and wheat bran. The diurnal patterns of volatile fatty acids and ammonia concentrations, and the numbers of protozoa in rumen fluid were determined. The numbers of protozoa reached values of 5 X 10(4)/ml for holotrichs (large ciliates) mainly Isotricha and Dasytricha spp and 4 X 10(5) for smaller protozoa, mainly Entodinia (small ciliates). 3. A method was developed which allowed large ciliate protozoa in rumen fluid to be separated from plant material and bacteria and concentrated in a relatively uncontaminated form. Analysis of these protozoa indicated that 1.8 X 10(5) large ciliates contained 1 mg nitrogen and approximately 32 mg dry matter. 4. A labelled preparation consisting mainly of large ciliates (principally Isotricha spp.) was obtained by incubating isolated protozoa in rumen fluid (free of plant materials) containing [14C-methyl]choline and then isolating them by sedimentation and differential centrifugation. 5. A portion of the preparation containing labelled protozoa was incubated in vitro with rumen fluid to determine the turnover of 14C-labelled metabolites. There was no apparent dilution of the label in the protozoa over a 22 h period. 6. A major portion of the preparation containing labelled protozoa was returned to the rumen of each of the donor cattle as a single injection. The specific radioactivity in the large protozoa (microCi/mg N) was monitored frequently for over 30 h, and thereafter daily for a further 12 d. The kinetics of tracer dilution were analyzed to give estimates of the size of the pool of these large ciliates in the rumen (24-46 g N), and of their apparent rate of turnover. 7. In contrast to the slow turnover of the large ciliates, the rate of turnover of the rumen fluid pool (approximately 54 1), estimated from the rate of dilution of polyethylene glycol, was considerably faster. Large ciliates were therefore selectively retained within the rumen. | {
"pile_set_name": "PubMed Abstracts"
} |
Best face forward: similarity effects in repetition priming of face recognition.
Two experiments examined the graded similarity effect in the repetition priming of familiar face recognition. From the model of repetition priming proposed by Burton, Bruce, and Johnston (1990) it was predicted that similarity effects may be a confound of stimulus preparation. Experiment 1 was used to discount this hypothesis, but failed to replicate a pattern of graded priming related to the similarity of prime and target faces. Experiment 2 attempted a more extensive investigation using two different measures of prime-target similarity. The results replicated Ellis, Young, Flude, and Hay's (1987) finding that similar primes confer more priming than dissimilar ones, but found no correlation between amount of priming and the degree of prime-target resemblance for either similarity metric used. In view of these findings the mechanism of repetition priming in familiar face recognition is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Saliva secretion following long-term antidepressant treatment with nortriptyline controlled by plasma levels.
Eight patients undergoing antidepressant therapy with nortriptyline for 1--4 years were investigated. The period of the investigation was 7 weeks and included a 2-week placebo period, blind for the patients. Total saliva secretion measurement, the nortriptyline plasma level, and signs and symptoms of depression and side effects were obtained once a week during the study. The results of the investigation were: (1) long-term treatment with nortriptyline is followed by hyposecretion or xerostomia, (2) the reduction of the secretion is reversible, (3) re-establishment of treatment with dosage leading to the same serum level of nortriptyline is immediately followed by a drop in saliva secretion, and (4) the changes in salivary secretion are useful as an indicator of side effects. The practical importance of the investigation is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Sialylated human apolipoprotein E (apoEs) is preferentially associated with neuron-enriched cultures from APOE transgenic mice.
Mice transgenic for human APOE2, E3, and E4 alleles express native 34-kDa human apoE and two sialylated apoE isoproteins with approximate molecular weights of 37 kDa (apoEs) and 39 kDa (apoEs2) in brain. These multiple apoE/apoEs/apoEs2 band patterns on Western blot are also observed in human brain, but are not seen in wild-type mouse brain. Both the 37-kDa apoEs and 39-kDa apoEs2 are coprecipitated with native 34-kDa apoE by antibody to human apoE. Neuraminidase digestion eliminates the 37- and 39-kDa forms and results in a downward shift in the bands to the position of the 34-kDa native form. These sialylated apoE isoproteins are found preferentially associated with neurons and contribute significantly (50-60%) to the total neuronal apoE in neuronal cultures from transgenic mice, while only 5-10% of total apoE is sialylated in cultures enriched in glial cells. In situ hybridization and immunocytochemistry demonstrate apoE mRNA and apoE immunoreactivity are predominantly located in cell soma of neurons, not in neuronal processes. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparison of two methods for selection of out of hospital treatment in patients with acute pulmonary embolism.
The aim of this study is to compare the performance of two clinical decision rules to select patients with acute pulmonary embolism (PE) for outpatient treatment: the Hestia criteria and the simplified Pulmonary Embolism Severity Index (sPESI). From 2008 to 2010, 468 patients with PE were triaged with the Hestia criteria for outpatient treatment: 247 PE patients were treated at home and 221 were treated as inpatients. The outcome of interest was all-cause 30-day mortality. In a post-hoc fashion, the sPESI items were scored and patients were classified according to the sPESI in low and high risk groups. Of the 247 patients treated at home, 189 (77%) patients were classified as low risk according to the sPESI and 58 patients (23%) as high risk. In total, 11 patients died during the first month; two patients treated at home and nine patients treated in-hospital. None of the patients treated at home died of fatal PE. Both the Hestia criteria and sPESI selected >50% of patients as low risk, with good sensitivity and negative predictive values for 30-day mortality: 82% and 99% for the Hestia criteria and 91% and 100% for the sPESI, respectively. The Hestia criteria and the sPESI classified different patients eligible for outpatient treatment, with similar low risks for 30-day mortality. This study suggests that the Hestia criteria may identify a proportion of high risk sPESI patiennts who can be safely treated at home, this however requires further validation. | {
"pile_set_name": "PubMed Abstracts"
} |
The role of myeloperoxidase in the microbicidal activity of polymorphonuclear leukocytes.
Myeloperoxidase (MPO), H2O2 and a halide form a powerful antimicrobial system effective against bacteria, fungi, viruses and mammalian cells. After phagocytosis, MPO is released into the phagosome from adjacent granules where it interacts with H2O2 generated either by leukocytic or microbial metabolism and a halide such as chloride or iodide to form agents toxic to the ingested organisms. Evidence for H2O2 and MPO participation in the microbicidal activity of polymorphonuclear leukocytes (PMNs) has been obtained from patients with neutrophil dysfunction. In chronic granulomatous disease, PMNs have a microbicidal defect associated with the absence of the respiratory burst. The importance of H2O2 deficiency in the PMN dysfunction is emphasized by its reversal by H2O2. PMNs which lack MPO also have a major fungicidal and bactericidal defect. Bactericidal activity is particularly low during the early postphagocytic period, after which the organisms are killed. Although emphasizing the importance of MPO-mediated antimicrobial systems particularly during the early postphagocytic period, these findings also indicate the presence of MPO-independent systems which develop slowly but are ultimately effective. The MPO-independent antimicrobial systems may be oxygen-dependent or oxygen-independent. The acetaldehyde-xanthine oxidase system has been used as a model of the MPO-independent, oxygen-dependent antimicrobial systems of the PMN. A microbicidal effect by this system was observed which was inhibited by superoxide dismutase, catalase and scavengers of hydroxyl radicals (OH') and singlet oxygen (1O2). The microbicidal activity of acetaldehyde and xanthine oxidase is increased considerably by MPO and chloride. The formation of ethylene from methional or 2-oxo-4-methylthiobutyric acid by PMNs has been regarded as evidence for OH' formation. We have found ethylene formation to be largely dependent on MPO and evidence for the initiation of ethylene formation by 1O2 has been obtained. Both the xanthine oxidase system and the MPO-H2O2-halide system convert diphenylfuran into cis-dibenzoylethylene, an effect which is compatible with, although not proof of, the formation of 1O2 by these systems. | {
"pile_set_name": "PubMed Abstracts"
} |
Therapeutic plasma exchange in the treatment of exertional heat stroke and multiorgan failure.
Exertional heat stroke (EHS) results in a constellation of systemic inflammatory responses resulting in multiorgan failure and an extremely high mortality. We present the case of an 11-year-old obese male who suffered EHS with rhabdomyolysis and concurrent renal, pulmonary, and hepatic failure. Conventional therapies including continuous veno-venous hemodiafiltration (CVVHDF) were ineffective in preventing ongoing deterioration in clinical status. Liver biopsy was reported as "extensive hepatocyte ballooning" and liver-kidney transplantation was tentatively planned. The addition of therapeutic plasma exchange using the Prismaflex® system (Gambro, Lakewood, CO, USA) resulted in a reversal of the inflammatory process and recovery from multiorgan failure. Liver biopsy was not a reliable indicator of irreversible hepatic injury. | {
"pile_set_name": "PubMed Abstracts"
} |
Expression profiling shows differential molecular pathways and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma.
Serrated adenocarcinoma (SAC) is a recently recognized colorectal cancer (CRC) subtype accounting for 7.5 to 8.7% of CRCs. It has been shown that SAC has a poorer prognosis and has different molecular and immunohistochemical features compared with conventional carcinoma (CC) but, to date, only one previous study has analyzed its mRNA expression profile by microarray. Using a different microarray platform, we have studied the molecular signature of 11 SACs and compared it with that of 15 matched CC with the aim of discerning the functions which characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a validation set of 70 SACs and 70 CCs to assess their diagnostic and prognostic values. Microarray data showed a higher representation of morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related functions and also an overexpression of fascin1 (actin-bundling protein associated with invasion) and the antiapoptotic gene hippocalcin in SAC all of which were validated both by quantitative real-time PCR (qPCR) and immunohistochemistry. Fascin1 expression was statistically associated with KRAS mutation with 88.6% sensitivity and 85.7% specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity = 100%). Evaluation of these markers in CRCs showing histological and molecular characteristics of high-level microsatellite instability (MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular profiling demonstrates that SAC shows activation of distinct signaling pathways and that immunohistochemical fascin1 and hippocalcin expression can be reliably used for its differentiation from other CRC subtypes. | {
"pile_set_name": "PubMed Abstracts"
} |
Recombinant human granulocyte/macrophage colony-stimulating factor enhances monocyte cytotoxicity and secretion of tumor necrosis factor alpha and interferon in cancer patients.
The colony-stimulating factors (CSFs) promote the proliferation and differentiation of hematopoietic precursors and more recently have been shown to amplify the functions of mature phagocytes in vitro. In this study recombinant human granulocyte/macrophage colony-stimulating factor (rGM-CSF) was administered to cancer patients to determine whether the cytotoxic and secretory activity of their blood monocytes could be enhanced. Patients with refractory neoplastic disease were treated with rGM-CSF either as a single bolus or as a constant infusion for 14 days at either 100 or 500 micrograms/m2 per day. As has been reported by others, the number of peripheral blood monocytes and granulocytes rose markedly in a dose-response fashion during infusion with rGM-CSF. The functional capacity of monocytes was increased by rGM-CSF, since the cytotoxicity of monocytes against antibody-coated xenogeneic cells was increased during the constant infusion compared to baseline. In addition, monocytes harvested during the constant infusion and stimulated with lipopolysaccharide (LPS) in vitro secreted increased quantities of tumor necrosis factor alpha (TNF-alpha) and interferon (IFN). These data indicate that rGM-CSF can enhance both the number and the function of peripheral blood monocytes in vivo. | {
"pile_set_name": "PubMed Abstracts"
} |
Is it normal to be a principal mindreader? Revising theories of social cognition on the basis of schizophrenia and high functioning autism-spectrum disorders.
Schizophrenia and high functioning autism-spectrum disorders (ASD) are neurodevelopmental conditions that mainly impair social competence, while general intelligence (IQ) is spared. Both disorders have a strong ancillary role in theoretical research on social cognition. Recently the debate has started to be inflected by embodied and phenomenological approaches, which claim that the standard portrayal of all social understanding as so-called 'mindreading', i.e. the attribution of mental states to others in the service of explaining and predicting their behavior, is misguided. Instead it is emphasized that we normally perceive others directly as conscious and goal-directed persons, without requiring any theorizing and/or simulation. This paper evaluates some of the implications of abnormal experiences reported by people with schizophrenia and ASD for the current debate in cognitive science. For these people the practice of explicit mindreading seems to be a compensatory strategy that ultimately fails to compensate for - and may even exacerbate - their impairment of intuitive and interactive social understanding. Phenomenological psychopathology thereby supports the emerging view that 'mindreading' is not the principal form of normal social understanding. | {
"pile_set_name": "PubMed Abstracts"
} |
Dynameomics: protein dynamics and unfolding across fold space.
All currently known structures of proteins together define 'protein fold space'. To increase the general understanding of protein dynamics and protein folding, we selected a set of 807 proteins and protein domains that represent 95% of the currently known autonomous folded domains present in globular proteins. Native state and unfolding simulations of these representatives are now complete and accessible via a novel database containing over 11 000 simulations. Because protein folding is a microscopically reversible process, these simulations effectively sample protein folding across all of protein fold space. Here, we give an overview of how the representative proteins were selected and how the simulations were performed and validated. We then provide examples of different types of analyses that can be performed across our large set of simulations, made possible by the database approach. We further show how the unfolding simulations can be used to compare unfolding of structural elements in isolation and in different structural contexts, using as an example a short, triple stranded β-sheet that forms the WW domain and is present in several larger unrelated proteins. | {
"pile_set_name": "PubMed Abstracts"
} |
Hypoxia induces an opsonic mismatch on the polymorphonuclear leukocyte surface-reversal via Arg-Gly-Asp-Ser-mediated adhesion.
Hypoxia remains an important clinical problem and affects neutrophil oxygen-dependent microbicidal pathways. For adequate PMN-cidal activity to occur, two sets of opsonic receptors (FcR, CD16, CD32w; complement receptors, CD35, CD11b/CD18) must be expressed on the cell surface. We hypothesized that hypoxia would adversely affect receptor expression and that the biological surface that the PMN were adhered to would modulate the effect of hypoxia on these receptors. PMN were adhered in the presence of buffer, fibronectin, Arg-Gly-Asp-Ser (RGDS), or laminin followed by assessment of PMN FcR and complement receptors using 125I-labeled monoclonal antibodies directed against these receptors. Hypoxia reduced PMN CD16 and CD32w but not CD35 and CD11b/CD18 expression. Decreasing buffer pO2 led to corresponding decreases in CD16 and CD32w expression. RGDS but not fibronectin or laminin restored CD16 and CD32w expression in the presence of hypoxia. Monensin but not cycloheximide inhibited RGDS restoration of CD16 and CD32w. (cpm bound: CD16, 958 +/- 123 vs 1602 +/- 193; CD32w, 1481 +/- 173 vs 2215 +/- 382 for hypoxia buffer+RGDS +/- monensin.) These results demonstrate that: (1) acute hypoxia creates an opsonic mismatch by reducing CD16 and CD32w without affecting complement receptors CR1 and CR3 (CD35, CD11b/CD18); (2) matrix proteins modulate the effect of acute hypoxia on PMN FcR; (3) the RGDS-binding epitope of fibronectin significantly restores PMN FcR in the face of acute hypoxia; and (4) RGDS upregulates FcR expression during acute hypoxia by increasing receptor recycling to the cell surface. | {
"pile_set_name": "PubMed Abstracts"
} |
Rapid titrimetric and spectrophotometric methods for salbutamol sulphate in pharmaceuticals using N-bromosuccinimide.
One titrimetric and two spectrophotometric methods which are simple, sensitive and rapid are described for the assay of salbutamol sulphate (SBS) in bulk drug and in tablet dosage forms using N-bromosuccinimide (NBS) and two dyes, rhodamine-B and methylene blue, as reagents. In titrimetry, aqueous solution of salbutamol sulphate is treated with a measured excess of NBS in acetic acid medium and after the oxidation of SBS is complete, the unreacted oxidant is determined iodometrically. Spectrophotometric methods entail addition of a known excess of NBS in acid medium followed by the determination of residual oxidant by reacting with a fixed amount of either rhodamine B and measuring the absorbance at 555 nm (method A) or methylene blue and measuring the absorbance at 665 nm (method B). In all methods, the amount of NBS reacting corresponds to the amount of SBS content. Titrimetric method is applicable over 1.74 x 10(-4) - 8.68 x 10(-4) mol L(-1) range and the reaction stoichiometry is found to be 1:6 (SBS:NBS). In spectrophotometric methods, the absorbance is found to increase linearly with the concentration of SBS, which is corroborated by the correlation of coefficients of 0.9993 and 0.9988 for method A and method B, respectively. The systems obey Beer's law for 0.25-1.75 microg mL(-1) (method A) and 0.5-5.0 microg mL(-1) (method B). The calculated apparent molar absorptivity values were found to be 2.10 x 10(5) and 6.16 x 10(4) L mol(-1) cm(-1), for method A and method B, respectively. The limits of detection and quantification are also reported for both spectrophotometric methods. Intra-day and inter-day precision and accuracy for the developed methods were evaluated. The methods were successfully applied to the assay of SBS in tablet and capsule formulations and the results were statistically compared with those of a reference method. No interference was observed from common tablet adjuvants. The accuracy and reliability of the methods were further ascertained by recovery experiments via the standard-addition technique. | {
"pile_set_name": "PubMed Abstracts"
} |
Enantioselective total synthesis of desbromoarborescidines A-C and the formal synthesis of (S)-deplancheine.
Starting from Boc-protected tryptamine and (S)-tetrahydro-5-oxo-2-furancarboxylic acid, facile enantioselective total synthesis of desbromoarborescidines A-C and the formal synthesis of (S)-deplancheine have been accomplished via a common intermediate (S)-indolo[2,3-a]quinolizine. Synthesis of enantiomerically pure (S)-acetoxyglutarimide, stereoselective reductive intramolecular cyclization, hydroxyl group-assisted in situ N-Boc-deprotection, selective deoxygenation of the xanthate ester, and lactam hydrolysis followed by an appropriate exchange of nitrogen regioselectivity in intramolecular cyclization were the decisive steps. | {
"pile_set_name": "PubMed Abstracts"
} |
Primary malignant melanoma of the esophagus presenting with massive hematemesis.
A 66-year-old Japanese man was admitted to our hospital, presenting with massive hematemesis. Emergency endoscopy revealed a bleeding tumor at the esophagogastric junction. The endoscopic appearance of the tumor was that of a Borrmann 2-like tumor, with a brownish-black discoloration. Bioptic histology confirmed the diagnosis of malignant melanoma. Atypical melanocytes with junctional changes were also found at a small pigmented patch in the lower esophagus, separate from the gross tumor. Melanocytosis was noted in the adjacent esophageal epithelium in the resection specimen following surgery. No primary lesion was found elsewhere, even in the patient's skin. These pathologic findings support the possibility of multicentric occurrence of malignant melanoma in esophageal melanocytosis. The patient is alive 11 months later, with multiple liver metastases. Massive hematemesis is an unusual presentation of primary malignant melanoma of the esophagus. | {
"pile_set_name": "PubMed Abstracts"
} |
Glycemic effects of vildagliptin and metformin combination therapy in Indian patients with type 2 diabetes: an observational study.
To analyze the glycemic response of Indian patients with type2 diabetes mellitus (T2DM) to combination therapy with vildagliptin and metformin and compare our data with those of clinical trials. In a retrospective study of the hospital database, the glycemic control of 280 patients with T2DM who were either on a once- or twice-daily regimen of combination therapy with vildagliptin 50 mg and metformin 500 mg was analyzed. The mean duration of follow-up of the patients was 16.8 months. There was a reduction in fasting plasma glucose (FPG) of 1.52 ± 0.79 and 1.88 ± 0.87 mmol/L in the once- and twice-daily groups, respectively (both P < 0.0001) from baseline to last visit. The reduction in postprandial plasma glucose (PPPG) in the once- and twice-daily groups was 3.98 ± 1.72 and 4.33 ± 1.88 mmol/L, respectively (both P < 0.0001), whereas the reduction in HbA1c was 1.41 ± 1.39% and 1.90 ± 1.49%, respectively (both P < 0.0001). The differences in the reductions achieved in FPG and HbA1c with the two dosing regimens were significant. Although the present retrospective study shows a robust response to the combination of vildagliptin and metformin in Indian patients, more multicenter studies from India with a greater number patients are necessary to confirm this finding. | {
"pile_set_name": "PubMed Abstracts"
} |
[Prognostic significance of total blood cholesterol level and the possibility of dietary correction of hypercholesterolemia in the population].
In a population of males aged 40-59 years, a routine epidemiological survey was performed, which was followed by a 5-year follow-up to examine the mortality rates and incidence of myocardial infarction and stroke treated by an active prophylactic measure program (Group 1) and conventional regimen (Group 2). The total cholesterol levels of 260 mg/dl or more were found to be of highly prognostic value to death from all causes, largely cardiovascular diseases, to development of myocardial infarction, stroke, and to higher risk of fatal cases of the diseases. It was ascertained that it was difficult to modify the dietary habits in subjects of mature age. By the end of the fifth follow-up year, the examined patients from Group 1 showed a reduction in the mean level of total cholesterol and hypercholesterolemia rates, following by a decrease in total and cardiovascular mortality by 6.5 and 5.7%, respectively, the incidence of myocardial infarction and stroke and the risk of death from these complications becoming lower. | {
"pile_set_name": "PubMed Abstracts"
} |
Experimental clonorchiasis in dogs: CT findings before and after treatment.
To determine whether disease activity in clonorchiasis can be assessed with dynamic computed tomography (CT). Ten dogs infected with metacercariae of Clonorchis sinensis underwent serial dynamic CT examinations. Five dogs were sacrificed 14 weeks after infection, and another five infected dogs were treated with praziquantel at the 14th week and continued to undergo CT examinations until death or sacrifice at the 25th (n = 1) or 40th week (n = 4). CT images were evaluated for dilatation of the bile ducts, contrast enhancement of bile duct walls and adjacent hepatic parenchyma, visualization of flukes within the bile ducts, and presence of calcifications. Changes in CT findings were analyzed statistically by using a mixed linear model and a generalized estimating equations model. Dilatation of the bile ducts, contrast enhancement of the ductal walls, transient hepatic attenuation differences, and flukes per se were observed at CT from the 2nd through the 5th week, were most apparent between the 5th and 13th weeks, and disappeared or decreased markedly in degree after treatment in all dogs (P <.05). Nodular calcifications were observed at CT after treatment in two dogs. Histopathologic examination revealed proliferation and enlargement of arteries in the periductal area and the portal tracts and congestion of hepatic sinusoids during the acute phase. Treatment was associated with periductal hyalinization, degeneration of the periductal arteries, and calcification of the ductal epithelium. Disease activity in experimental canine clonorchiasis can be assessed with dynamic CT. | {
"pile_set_name": "PubMed Abstracts"
} |
NPY--an endearing journey in search of a neurochemical on/off switch for appetite, sex and reproduction.
Although a dynamic link between the two innate drives, appetite for food and the urge to reproduce, in vertebrate evolution has been known for a long time, a distinct neurochemical pathway mediating this integration has only recently been appreciated. Study of the precise anatomy of the neural track began in the early to mid 20th century after the sites of genesis of the two instincts were localized to the hypothalamus. This report narrates the birth and fruition to maturity of insights into the commonality of hypothalamic neuropeptide Y (NPY) signaling for the two instinctual drives along two distinct pathways. | {
"pile_set_name": "PubMed Abstracts"
} |
CT/MRI Fusion for Vascular Mapping and Navigated Resection of a Paraspinal Tumor.
Computed tomography/magnetic resonance imaging (CT/MRI) fusion is used increasingly in the surgical treatment of cranial pathology. The merging of these complementary modalities provides excellent visualization of the bony anatomy and clear delineation of the soft tissues, including neurovascular structures. To our knowledge, the application of CT/MRI fusion for the surgical management of spinal pathology has not been reported previously. A 70-year-old woman presented with a paraspinal tumor that originated from the right psoas muscle and extended into the lumbar neuroforamina, with intricate involvement of the lumbar plexus and retroperitoneal vasculature. CT/MRI fusion was used to map out the vessels surrounding the tumor and for intraoperative navigation during resection of this invasive paraspinal tumor. This case highlights both the feasibility and the advantages of applying CT/MRI fusion technology to the surgical treatment of spinal pathology. | {
"pile_set_name": "PubMed Abstracts"
} |
Patterns of molecular evolution of RNAi genes in social and socially parasitic bumblebees.
The high frequency of interactions amongst closely related individuals in social insect colonies enhances pathogen transmission. Group-mediated behavior supporting immune defenses tends to decrease selection acting on immune genes. Along with low effective population sizes this might result in relaxed constraint and rapid evolution of immune system genes. Here, we show that antiviral siRNA genes show high rates of molecular evolution with argonaute 2, armitage and maelstrom evolving faster in social bumblebees compared to their socially parasitic cuckoo bumblebees that lack a worker caste. RNAi genes show frequent positive selection at the codon level additionally supported by the occurrence of parallel evolution. Their evolutionary rate is linked to their pathway specific position with genes directly interacting with viruses showing the highest rates of molecular evolution. We suggest that higher pathogen load in social insects indeed drives the molecular evolution of immune genes including antiviral siRNA, if not compensated by behavior. | {
"pile_set_name": "PubMed Abstracts"
} |
Assessment of diffuse transmission and reflection modes in near-infrared quantification, part 2: DIFFuse reflection information depth.
Near-infrared spectroscopy offers tremendous advantages for pharmaceutical manufacturing as a fast and nondestructive method of quantitative and qualitative analysis. Content uniformity (end-product analytics) and process analytics are two important applications of the method. Diffuse reflection (DR) information depth (vertical sampling span) assessment is of equal importance in content prediction applications and to understand the effect of inhomogeneities in the sample. Three experiments were conducted: (a) 0.5 to 10.0 mm incremental thickness MCC tablets with constant porosity, (b) MCC/phenylbutazone (PBZ) double-layered (DL) tablets (PBZ layer 0%-100% in 0.5 mm steps), and (c) Comparison of placebo and 30% caffeine tablet cores with incremental film coating (film thickness of 0-0.35 mm). Incremental thickness and cluster analysis of DL tablets showed that DR information depth was <0.5 mm, whereas the data fitting from incremental coating showed that signal drop reached 50% at 0.05 to 0.07 mm, depending on the wavenumber and 90% signal drop (10% information content) can be seen between 0.20 and 0.25 mm without extrapolation. These results mean that DR mode for pharmaceutical tablets obtains spectral information from the very surface, and radiation is barely reflected back from beyond thin-film coatings, making it less useful than diffuse transmission mode for core content analysis, especially for thick-coated, multilayer, multicore, or highly inhomogeneous tablets. | {
"pile_set_name": "PubMed Abstracts"
} |
Compliance of the total respiratory system in healthy preterm and full-term newborns.
The compliance of the total respiratory system (CRS) was determined by the occlusion technique during expiration in 19 preterm newborns (NB) over 31 weeks of gestational age (mean, 34 +/- 1.5 SD) and in 20 full-term NB. Postnatal age ranged from 1 to 28 days. No sedation was used during the test. In absolute terms, CRS was significantly greater (P less than 0.01) in full-term than in preterm NB (3.17 +/- 0.71 ml/cm H2O vs 2.37 +/- 0.81 ml/cm H2O). When normalized for body weight, length cubed, [corrected] body surface area, and the Quetelet index (body weight/length squared) [corrected], CRS was similar in preterm and full-term NB. These results suggest that, normalized for biometric data, passive elastic properties of the total respiratory system are similar in full-term and preterm NB, at least in the gestation age range studied. | {
"pile_set_name": "PubMed Abstracts"
} |
Therapeutic response to phenelzine in patients with panic disorder and agoraphobia with panic attacks.
The therapeutic response to phenelzine sulfate was evaluated during 6 months' treatment of 35 outpatients meeting DSM-III criteria for panic disorder or agoraphobia with panic attacks. The possible influence of nonspecific predictors of drug efficacy and some biochemical parameters were investigated. Therapeutic response was assessed on standardized rating scales. Agoraphobic patients showed a significantly higher frequency of panic attacks when compared to the subjects with uncomplicated panic disorder. Phenelzine treatment blocked panic attacks in 100% of the patients with panic disorder and in 94.7% of the agoraphobics. Anticipatory anxiety and avoidant behavior improved markedly, although not statistically significantly, in 73.6% of the agoraphobics. | {
"pile_set_name": "PubMed Abstracts"
} |
The OxyContin crisis: problematisation and responsibilisation strategies in addiction, pain, and general medicine journals.
OxyContin(®) (Purdue Pharma, L.P., Stamford, CT) is now widely regarded as a drug of abuse fueling a larger opioid health crisis. While coverage in the North American press about OxyContin overwhelmingly focused upon the problems of related crime and addiction/misuse and the perspectives of law enforcement officials and police, coverage in those fields of medicine most intimately concerned with OxyContin-pain medicine and addiction medicine-was more nuanced. In this article, we draw upon the constructivist social problems tradition and Hunt's theory of moral regulation in a qualitative analysis of 24 medical journal articles. We compare and contrast pain medicine and addiction medicine representations of the OxyContin problem, the agents responsible for it, and proposed solutions. While there are some significant differences, particularly concerning the nature of the problem and the agents responsible for it, both pain medicine and addiction medicine authors 'take responsibility' in ways that attempt to mitigate the potential appropriation of the issue by law enforcement and regulatory agencies. The responses of pain medicine and addiction medicine journal articles represent strategic moves to recapture lost credibility, to retain client populations and tools necessary to their jobs, and to claim a seat at the table in responding to the OxyContin crisis. | {
"pile_set_name": "PubMed Abstracts"
} |
Health as foreign policy: harnessing globalization for health.
This paper explores the importance for health promotion of the rise of public health as a foreign policy issue. Although health promotion encompassed foreign policy as part of 'healthy public policy', mainstream foreign policy neglected public health and health promotion's role in it. Globalization forces health promotion, however, to address directly the relationship between public health and foreign policy. The need for 'health as foreign policy' is apparent from the prominence public health now has in all the basic governance functions served by foreign policy. The Secretary-General's United Nations (UN) reform proposals demonstrate the importance of foreign policy to health promotion as a core component of public health because the proposals embed public health in each element of the Secretary-General's vision for the UN in the 21st century. The emergence of health as foreign policy presents opportunities and risks for health promotion that can be managed by emphasizing that public health constitutes an integrated public good that benefits all governance tasks served by foreign policy. Any effort to harness globalization for public health will have to make health as foreign policy a centerpiece of its ambitions, and this task is now health promotion's burden and opportunity. | {
"pile_set_name": "PubMed Abstracts"
} |
[Intranasal absorption of rivastigmine hydrogen tartrate and brain targeting evaluation].
To investigate factors influencing the intranasal absorption of rivastigmine hydrogen tartrate (RHT), we studied the pharmacokinetics of RHT after intranasal administration and evaluated its brain targeting behavior. In situ rat nasal perfusion model was used in the study and pH impact was examined on the intranasal absorption of RHT. High performance liquid chromatography (HPLC) method was established to measure RHT concentration in the plasma and brain tissue after intranasal and intravenous administration. The pharmacokinetic parameters, drug targeting index(DTI), and nose-to-brain direct transport percentage (DTP) were calculated. It was demonstrated that the intranasal absorption mechanism of RHT was passive diffusion. The absorption rate was highest at pH 6.0. The absolute bioavailability of intranasally administrated RHT was 73.58%. Compared with that of intravenous administration, RHT absorption into the brain was faster and more efficient after intranasal delivery, and the DTI value was 195.27% of intravenous injection. Moreover, 48.79% of the drug can be absorbed directly from the nose into the brain without systematic circulation. Meanwhile, drug elimination half-time in the brain was prolonged by 1.4 fold compared to that of intravenous injection. In conclusion, intranasal administration of RHT not only improves drug absorption into the system, but also enhances drug absorption rate and content in the brain remarkably, which is an advantage in the treatment of central nervous system-related diseases. | {
"pile_set_name": "PubMed Abstracts"
} |
Chronic migraine.
Chronic migraine is a disabling neurologic condition that affects 2% of the general population. Patients with chronic migraine have headaches on at least 15 days a month, with at least eight days a month on which their headaches and associated symptoms meet diagnostic criteria for migraine. Chronic migraine places an enormous burden on patients owing to frequent headaches; hypersensitivity to visual, auditory, and olfactory stimuli; nausea; and vomiting. It also affects society through direct and indirect medical costs. Chronic migraine typically develops after a slow increase in headache frequency over months to years. Several factors are associated with an increased risk of transforming to chronic migraine. The diagnosis requires a carefully performed patient interview and neurologic examination, sometimes combined with additional diagnostic tests, to differentiate chronic migraine from secondary headache disorders and other primary chronic headaches of long duration. Treatment takes a multifaceted approach that may include risk factor modification, avoidance of migraine triggers, drug and non-drug based prophylaxis, and abortive migraine treatment, the frequency of which is limited to avoid drug overuse. This article provides an overview of current knowledge regarding chronic migraine, including epidemiology, risk factors for its development, pathophysiology, diagnosis, management, and guidelines. The future of chronic migraine treatment and research is also discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Electronic and steric effects on the mechanism of the inverse electron demand Diels-Alder reaction of 2-aminopyrroles with 1,3,5-triazines: identification of five intermediates by 1H, 13C, 15N, and 19F NMR spectroscopy.
The inverse electron demand Diels-Alder (IEDDA) reaction of 1-tert-butyl-2-aminopyrrole with 2,4,6-tris(trifluoromethyl)-1,3,5-triazine in THF-d(8) to give a pyrrolo[2,3-d]pyrimidine was studied by (1)H, (13)C, (15)N, and (19)F NMR spectroscopy, and five intermediates were identified. A zwitterion was the first intermediate detected, and it cyclized to a tricyclic adduct and its conjugate acid. It also gave a neutral imine via a proton switch. The tricyclic adduct underwent a retro-Diels-Alder reaction, but the expected CF(3)CN was not detected. NMR indicated that the amino group of the 2-aminopyrrole was bonded to the CF(3)CN to form a trifluoroacetoamidinium ion. The products of the retro-Diels-Alder reaction reacted rapidly with each other to give the final intermediate observed. Acid-catalyzed loss of an amidine gave the final aromatic product. This is the first study in which direct experimental evidence for the order of the steps in the IEDDA cascade reaction of 1,3,5-triazines with amino-containing dienophiles has been obtained. This study and analogous 1,3-dipolar cycloaddition reactions, in which zwitterions have been detected or proposed, have two factors in common: electronic effects that stabilize the zwitterions and steric effects that inhibit their cyclization. | {
"pile_set_name": "PubMed Abstracts"
} |
Partial purification and characterization of a neurite outgrowth-promoting factor from chick heart-cell conditioned medium.
A factor in heart-cell conditioned medium (HCM), which adsorbs to the polyornithine-coated culture substratum, is known to induce neurite outgrowth from neurons in culture. This factor - termed the substrate conditioning factor (SCF) - was purified from chick HCM by fractionation with ammonium sulfate, DEAE Sepharose, and hydroxylapatite. A quantitative bioassay with dorsal root ganglion neurons in dissociated cell culture was used to determine the neurite outgrowth-promoting activity. More than 10,000-fold purification was achieved in the specific activity. SCF was sensitive to trypsin, and bound to the wheat germ lectin affinity column, indicating that SCF is a glycoprotein. The most purified fraction produced two major bands with apparent molecular weights of 360K and 220-240K on SDS-gel electrophoresis under reducing conditions. They were detected as radioactive bands when polypeptides synthesized by heart cells were metabolically labeled with [35S]methionine. These results suggest that the 360K and 220-240K components are required for the neurite outgrowth-promoting activity of SCF. | {
"pile_set_name": "PubMed Abstracts"
} |
Gamma-encephalography in the diagnosis of subdural effusions in infancy and childhood.
The results of the use of gamma-encephalography (GEG) as a diagnostic tool in a group of 28 patients with subdural effusions and 46 membranes confirmed at surgery are presented. 27 patients were submitted to bilateral surgical expolorations and 1 was unilaterally explored. Positive GEG: membranes were present in 34, in 8 the test was nonconclusive and there were 4 false-negatives. Negative GEG: membranes were absent in 6, 1 case was nonconclusive and 2 were false-positive tests. Therefore, from 28 patients with 46 membranes the GEG was correct in two thirds of the cases, it was nonconclusive in 9 cases and the image did not confirm the surgical findings in 6 cases (false-positive or false-negative). The results suggest that the presence of a medium or thick membrane almost always results in a positive image, whereas the presence of a thin membrane leads to a nonconclusive result or in some cases a false-negative one. The general data from the literature correlates well with the present series. | {
"pile_set_name": "PubMed Abstracts"
} |
Sequelae of massive fluid resuscitation in trauma patients.
The severely injured trauma patient presents to the critical care unit with multiple physiologic derangements. The sequelae of massive volume infusion necessary to restore tissue oxygenation in hemorrhagic shock include hypothermia, coagulopathies, electrolyte abnormalities, acidosis, and organ dysfunction. Therapeutic interventions are directed toward minimizing and reversing these derangements, rapid restitution of oxygen transport, and tissue oxygen uptake. | {
"pile_set_name": "PubMed Abstracts"
} |
In search for evidence: combining ad hoc survey, monitoring, and modeling to estimate the potential and actual impact of ground level ozone on forests in Trentino (Northern Italy).
A 5-year project was carried out over the period 2007-2011 to estimate the potential and actual ozone effect on forests in Trentino, Northern Italy (6207 km2) (Ozone EFFORT). The objective was to provide explicit answers to three main questions: (i) is there a potential risk placed by ozone to vegetation? (ii) are there specific ozone symptoms on vegetation, and are they related to ozone levels? (iii) are there ozone-related effects on forest health and growth? Different methods and techniques were adopted as follows: monitoring ozone levels, ad hoc field survey for symptoms on vegetation and chlorophyll-related measurements, modeling to upscale ozone measurements, ozone flux estimation, statistical analysis, and modeling to detect whether a significant effect attributable to ozone exists. Ozone effects were assessed on an ad hoc-introduced bioindicator, on spontaneous woody species, and on forest trees. As for question (i), the different ozone-risk critical levels for both exposure and stomatal flux were largely exceeded in Trentino, evidencing a potentially critical situation for vegetation. As for question (ii), specific ozone foliar symptoms related to ozone exposure levels were observed on the introduced supersensitive Nicotiana tabacum L. cv Bel-W3 and on the spontaneous, ozone-sensitive Viburnum lantana L., but not on other 33 species surveyed in the field studies. Regarding question (iii), statistical analyses on forest health (in terms of defoliation) and growth (in terms of basal area increment) measured at 15 forest monitoring plots and tree rings (at one site) revealed no significant relationship with ozone exposure and flux. Instead, a set of factors related to biotic and abiotic causes, foliar nutrients, age, and site were identified as the main drivers of forest health and growth. In conclusion, while ozone levels and fluxes in the investigated region were much higher than current critical levels, evidence of impact on vegetation-and on forest trees in particular-was limited. | {
"pile_set_name": "PubMed Abstracts"
} |
[Screening study methods use for substantiation of immune modulating therapy of hypergic inflammatory process in maxillofacial region].
With the help of flow cytometry it was shown that for patients with hypergic inflammatory process in maxillofacial region the reduction of lymphocytes relative number was typical as well as their absolute number reduction. Direct and very strong correlation was established between absolute lymphocytes number in peripheral blood and absolute number of CD3 and CD4 lymphocytes subpopulations by correlation analyses. The reduction of absolute lymphocytes number in peripheral blood let speak with more probability about the reduction of the number of CD3 and CD4 lymphocytes subpopulations and diagnose secondary immune deficit. | {
"pile_set_name": "PubMed Abstracts"
} |
Repeated triamcinolone acetonide injection in the treatment of upper-lid retraction in patients with thyroid-associated ophthalmopathy.
To evaluate the efficacy and safety of repeated subconjunctival injections of triamcinolone in the treatment of upper-lid retraction with thyroid-associated ophthalmopathy. Interventional controlled retrospective clinical study. We studied 23 eyes in 15 patients as the nontreatment control group and 35 eyes in 21 patients as the treatment group. In the treatment group, triamcinolone acetonide was subconjunctivally injected into each lid as 4 doses of 20 mg at 1-month intervals. After the treatment, the eyes were divided into 2 groups, response and nonresponse, based on the improvement in margin reflex distance. The eyes of the nontreatment group received no medicine. The eyes were examined regularly. The rate of spontaneous improvement in the nontreatment group was 17.4%. The mean rate of effectiveness was 68.6%. The improvement of upper-lid retraction was 2.31 mm (0 to 7 mm). The margin reflex distance was significantly smaller at 1 month after the initiation of treatment. Mean lid retraction time before treatment was 4.58 months in the response group versus 9.91 months in the nonresponse group. In the eyes presenting upper-lid retraction up to 6 months before treatment was initiated, the response rate was 83.3%. The response rate was only 36.4% when lid retraction developed more than 6 months before the procedure. The muscle thickness of the levator/superior rectus complex was significantly reduced after treatment in the response group (5.13 ± 0.85 mm at last follow-up vs. 5.69 ± 0.93 mm at baseline). Repeated subconjunctival injection of triamcinolone is an effective and safe treatment for upper-lid retraction due to thyroid-associated ophthalmopathy. | {
"pile_set_name": "PubMed Abstracts"
} |
Calf muscle pump impairment and delayed healing of venous leg ulcers: air plethysmographic findings.
There is a need for a diagnostic tool to predict clinical outcome of venous leg ulcer patients, as the prognosis of healing based on clinical data alone has not appeared to be satisfactory. Air plethysmographic assessment of calf muscle pump was performed in the supine and upright position in 129 patients with active ulcers on their legs. All patients were managed in a specialized leg ulcer clinic. Results of air plethysmography were compared to clinical data and time of healing of ulcers. Muscle pump failure was found in 42.6% of extremities (supine position, 33.3%; upright, 22.5%; both, 12.4%). Patients with insufficient pump were older, and their ulcers were larger. Failure of pump was found more often in patients who began the treatment after long, unsuccessful, non-specialized care. Healing time of ulcers was prolonged in cases with insufficient pump. Regarding the subgroups with good clinical prognosis (patients with small ulcers or with a short history of ulceration), it was found that insufficiency of muscle pump correlated with delayed healing. It could be summarized that venous leg ulcers associated with calf muscle failure were larger, long-standing, and that their healing even after specialized treatment was delayed. Impaired muscle pump function revealed in plethysmographic examination can be a prognostic factor of delayed healing of leg ulcer. Ulcers with poor prognosis according to plethysmographic findings, and no quick recovery after standard management, should be considered for advanced therapies. | {
"pile_set_name": "PubMed Abstracts"
} |
Simultaneous Determination of Rimsulfuron and Haloxyfop-P-methyl and Its Metabolite Haloxyfop in Tobacco Leaf by LC-MS/MS.
Background: Tobacco (Nicotiana tabacum L.), is an important economic crop. In China, the use of rimsulfuron and haloxyfop-P-methyl herbicides for weed management during the planting period is necessary to improve the production of tobacco. Objective: To establish and validate a quick, easy, cheap, effective, rugged, and safe LC-MS/MS method to determine rimsulfuron, haloxyfop-P-methyl, and haloxyfop in tobacco leaf samples. Methods: We optimized MS/MS conditions and chromatographic conditions for optimal detection conditions. The extraction solvent and sorbent were optimized, and the analysis of variance was applied to analyze the pretreatment method to obtain the optimal pretreatment conditions. Results: The validation results showed that the proposed method exhibited good linearity (R² > 0.9978), satisfactory recovery (72.51-101.60%) and low LOQ (0.02-1.00 mg/kg). The matrix effects of the three analytes in the two tobacco leaf matrixes were different. The dissipation results showed that the half-lives of rimsulfuron and haloxyfop-P-methyl in fresh tobacco leaf samples were ranged from 2.4 to 3.7 days. The final residues of rimsulfuron, haloxyfop-P-methyl, and haloxyfop in flue-cured tobacco leaf samples were all lower than the LOQ. Conclusions: The results demonstrate that the developed method could be used to detect rimsulfuron, haloxyfop-P-methyl, and haloxyfop in tobacco leaf matrixes. Highlights: A method for simultaneous determination of rimsulfuron, haloxyfop-P-methyl, and haloxyfop in tobacco leaf samples with high sensitivity has been established for the first time. | {
"pile_set_name": "PubMed Abstracts"
} |
[Management of aortoesophageal fistula due to thoracic aortic aneurysm].
Aortoesophageal fistula (AEF) is a rare but fatal disease without prompt diagnosis and treatment. A 82-year-old woman was admitted because of repeated hematemesis. Endoscopic examination suspected submucosal tumor with blood clot at the top on the mid-esophagus. The CT scan of the thorax and the aortography revealed a thoracic aortic aneurysm. AEF was diagnosed and the operation was performed. The ruptured aneurysm was resected and patched with Dacron graft. At the same time, subtotal esophagectomy with esophagostomy and gastrostomy were performed. The reconstruction at five weeks after operation induced oral intake. She died from an aspiration pneumonia five month later. | {
"pile_set_name": "PubMed Abstracts"
} |
The nutritional significance of root and tuber crop development as staples in the Caribbean community.
The competition between cereals and root crops as CARICOM staples is described. The move to substitute locally grown food for imported wheat is shown to favor root crop development in the region. Against this background, traditional nutrition-prompted objections to wheat substitution by root crops are examined. Evidence is cited to show the essential adequacy of protein in root crops, except plantain and cassava and for all humans except perhaps some infants. The low protein in cassava and plantain, it is proposed, can be easily overcome in the process of local root crop development. Finally, it is argued that there exists the potential to obtain cheap calories from root crops. This and the generation of economic activity among small farmers, concomitant with root crop development, are seen as possible indicators of good nutrition for the region in the future. | {
"pile_set_name": "PubMed Abstracts"
} |
Fluid management in traumatic shock: a practical approach for mountain rescue. Official recommendations of the International Commission for Mountain Emergency Medicine (ICAR MEDCOM).
Sumann, Günther, Peter Paal, Peter Mair, John Ellerton, Tore Dahlberg, Gregoire Zen-Ruffinen, Ken Zafren, and Hermann Brugger. Fluid management in traumatic shock: a practical approach for mountain rescue. High Alt. Med. Biol. 10:71-75, 2009.-The management of severe injuries leading to traumatic shock in mountains and remote areas is a great challenge for emergency physicians and rescuers. Traumatic brain injury may further aggravate outcome. A mountain rescue mission may face severe limitations from the terrain and required rescue technique. The mission may be characterized by a prolonged prehospital care time, where urban traumatic shock protocols may not apply. Yet optimal treatment is of utmost importance. The aim of this study is to establish scientifically supported recommendations for fluid management that are feasible for the physician or paramedic attending such an emergency. A nonsystematic literature search was performed; the results and recommendations were discussed among the authors and accepted by the International Commission for Mountain Emergency Medicine (ICAR MEDCOM). Diagnostic and therapeutic strategies are discussed, as well as limitations on therapy in mountain rescue. An algorithm for fluid resuscitation, derived from the recommendations, is presented in Fig. 1. Focused on the key criterion of traumatic brain injury, different levels of blood pressure are presented as a goal of therapy, and the practical means for achieving these are given. | {
"pile_set_name": "PubMed Abstracts"
} |
Permeability enhancing effects of the alkylglycoside, octylglucoside, on insulin permeation across epithelial membrane in vitro.
To evaluate the permeability enhancing effects of octylglucoside (OG) for molecules with poor absorption such as insulin by in vitro cell models. Transepithelial electrical resistance (TEER) was monitored to ensure monolayer integrity. Permeability was ascertained using paracellular markers. Markers and insulin were dissolved in Hanks balanced salt solution and placed on the apical side of the cells in Transwell(c) plates and allowed to diffuse under sink conditions. The effect of OG on the permeability of molecules across both monolayers was concentration and time dependent. Enhanced transport of the three molecules was observed across both monolayers treated with OG as compared to untreated monolayers. The effects of OG were reversible at low concentrations but there was permanent damage to cells at higher concentrations. Absorption enhancement was greater across T-84 monolayers compared to Caco-2 monolayers. The results indicate OG has potential as a permeability enhancer for poorly absorbed drugs with no significant damage to monolayers at low concentrations. Immediate attenuation in TEER upon exposure to OG indicates that permeability enhancing effects were likely to be associated with modulation of tight junctions suggesting the involvement of paracellular transport. | {
"pile_set_name": "PubMed Abstracts"
} |
ECOSYSTEM ASSESSMENT: Ecologists Hope to Avoid the Mistakes of Previous Assessment.
For ecologists, an attempt to assess the world's ecosystems (see main text) has a familiar ring to it. A few years ago, many of the same scientists poured their energy into the Global Biodiversity Assessment. But that exercise sank without a trace after participants failed to find a receptive audience. | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluation of the structural determinants of polymeric precipitation inhibitors using solvent shift methods and principle component analysis.
The presence of polymers within solid dose forms, such as solid dispersions, or liquid or semisolid formulations, such as lipid-based formulations, can promote the maintenance of drug supersaturation after dissolution or dispersion/digestion of the vehicle in the gastrointestinal tract. Transiently stable supersaturation delays precipitation, increases thermodynamic activity, and may enhance bioavailability and reduce variability in exposure. In the current study a diverse range of 42 different classes of polymers, with a total of 78 polymers across all classes, grades, and molecular weights were examined, to varying degrees, as potential polymeric precipitation inhibitors (PPIs) using a solvent shift method to initiate supersaturation. To provide a deeper understanding of the molecular determinants of polymer utility the data were also analyzed, along with a range of physicochemical descriptors of the polymers employed, using principle component analysis (PCA). Polymers were selectively tested for their ability to stabilize supersaturation for nine poorly water-soluble model drugs, representing a range of nonelectrolytes, weak acids, and weak bases. In general, the cellulose-based polymers (and in particular hydroxypropylmethyl cellulose, HPMC, and its derivatives) provided robust precipitation inhibition across most of the drugs tested. Subsequent PCA indicate that there is consistent PPI behavior of a given polymer for a given drug type, with clear clustering of the performance of polymers with each of the nonelectrolytes, weak bases, and weak acids. However, there are some exceptions to this, with some specific drug type-polymer interactions also occurring. Polymers containing primary amine functional groups should be avoided as they are prone to enhancing precipitation rates. An inverse relationship was also documented for the number of amide, carboxylic acid, and hydroxyl functional groups; therefore for general good PPI performance the number of these contained within the polymer should be minimized. Molecular weight is a poor predictor of performance, having only a minor influence, and in some cases a higher molecular weight enhances the precipitation process. The importance of ionic interactions to the ability of a PPI to stabilize the supersaturated state was demonstrated by the advantage of choosing a polymer with an opposite charge with respect to the drug. Additionally, when the polymer charge is the same as the supersaturated drug, precipitation is likely to be enhanced. A PCA model based on polymer molecular properties is presented, which has a central oval region where the polymer will general perform well across all three drug types. If the polymer is located outside of this region, then they either show compound-specific inhibition or enhance precipitation. Incomplete separation of the PPI performance based on the molecular properties on the polymers indicates that there are some further molecular properties that might improve the correlation. | {
"pile_set_name": "PubMed Abstracts"
} |
Role of Heat Shock Factors in Stress-Induced Transcription.
Heat shock proteins (HSP) are rapidly induced after stresses such as heat shock and accumulate at high concentrations in cells. HSP induction involves primarily a family of heat shock transcription factors (HSF) that bind the heat shock elements of the HSP genes and mediate transcription in trans. We discuss methods for the study of HSP binding to HSP promoters and the consequent increases in HSP gene expression in vitro and in vivo. | {
"pile_set_name": "PubMed Abstracts"
} |
Plesiomonas shigelloides Periprosthetic Knee Infection After Consumption of Raw Oysters.
Periprosthetic infections are a leading cause of morbidity after total joint arthroplasty. Common pathogens include Staphylococcus aureus, streptococcus, enterococcus, Escherichia coli, and Pseudomonas aeruginosa. However, there are many cases in which rare bacteria are isolated. This case report describes a periprosthetic knee infection caused by Plesiomonas shigelloides. In the United States, P shigelloides and 2 other Vibrionaceae family members, Vibrio vulnificus and Vibrio parahaemolyticus, are most often contracted from eating raw oysters and shellfish. P shigelloides usually causes a self-limiting watery diarrhea, but in immunosuppressed people it can cause septicemia. In this case report, a chemically and biologically immunosuppressed man consumed raw oysters and developed P shigelloides septicemia and acute periprosthetic knee infection that required surgical intervention. | {
"pile_set_name": "PubMed Abstracts"
} |
Case control study of antibodies to ENA in progressive systemic sclerosis patients.
Sixteen antibody to extractable nuclear antigen (anti-ENA) (+) and 16 anti-ENA(-) progressive systemic sclerosis (scleroderma, PS) patients were matched for disease duration, age, and sex in a case control study of antibody to ENA (anti-ENA) in scleroderma. Anti-ENA (+) PSS patients more frequently fulfill only minor criteria for PSS than anti-ENA (-) PSS controls (31% vs 0%). Anti-ENA(+) patients had less skin and muscle involvement (p less than 0.05) than their matched controls and tended to overlap more with other diseases (3 vs 0 patients). Besides antinuclear antibody and ENA, no significant serological differences were found between the 2 groups. | {
"pile_set_name": "PubMed Abstracts"
} |
Communicative and sensorimotor development of Down's syndrome children.
Imperative and declarative performative behavior was examined in nonretarded and Down's syndrome children operating at two stages of sensorimotor intelligence. In both groups, more advanced types of performative behavior generally associated with a higher sensorimotor stage. Relative to the nonretarded children of the same sensorimotor stages, the Down's syndrome children relied more heavily on gestures in their imperative and declarative usage. Evidence was also obtained suggesting that the correspondence between sensorimotor stage and performative behavior is closer at younger ages than at older ages. | {
"pile_set_name": "PubMed Abstracts"
} |
Infection dynamics of Centrocestus armatus cercariae (Digenea: Heterophyidae) to second intermediate fish hosts.
The infection dynamics of Centrocestus armatus cercariae with respect to second intermediate fish hosts were investigated using cercariae collected from naturally infected Semisulcospira libertina. Cercariae survival and infectivity were recorded at 2-hr intervals. Survival remained constant but decreased abruptly at 30 hr of age. An age-dependent model presented the best-fit curve for the survival data (r2 0.936), implying that cercariae tended to allocate resources equally among themselves and then died once those resources were depleted. Cercariae infectivity remained constant over the first 10 hr of life and then declined; an age-dependent model also provided a better fit (r2 = 0.956). The transmission rate of C. armatus cercariae to the fish host was relatively low near the time of emergence from the snail host but peaked at 85% after 1 hr and then maintained a plateau period until 5 hr of exposure to fish. The pattern of transmission was also investigated initially at varying densities of cercariae and then by maintaining a constant cercariae density but varying the total number. Results revealed that the pattern of transmission was frequency-dependent. | {
"pile_set_name": "PubMed Abstracts"
} |
Prevention of early-onset neonatal group B streptococcal disease with selective intrapartum chemoprophylaxis.
Most cases of neonatal group B streptococcal disease with early onset have an intrapartum pathogenesis. Attack rates are increased substantially in infants born to mothers with prenatal group B streptococcal colonization and various perinatal risk factors (premature labor, prolonged membrane rupture, or intrapartum fever). In a randomized controlled trial, we studied the effect of selective intrapartum prophylaxis with ampicillin in 160 such high-risk women. In infants born to mothers who received intravenous ampicillin during labor, as compared with controls who received no treatment, neonatal colonization with group B streptococci was present in 8 of 85 (9 percent) versus 40 of 79 (51 percent; P less than 0.001), colonization at multiple (greater than or equal to 3) sites was observed in 3 of 85 (4 percent) versus 24 of 79 (30 percent; P less than 0.001), and bacteremia occurred in none of 85 versus 5 of 79 (6 percent; P = 0.024). The side effects of ampicillin were limited to a single episode of urticaria in a mother who had no history of penicillin allergy. We conclude that intrapartum ampicillin prophylaxis in women with positive prenatal cultures for group B streptococci who have certain perinatal risk factors can prevent early-onset neonatal group B streptococcal disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Root production and root turnover in two dominant species of wet heathlands.
Root biomass production, root length production and root turnover of Erica tetralix and Molinia caerulea were estimated by sequential core sampling and by observations in permanent minirhizotrons in the field. Root biomass production, estimated by core sampling, was 370 (Erica) and 1080 (Molinia) g m-2 yr-1. This was for both species equal to aboveground production. Assuming steady-state conditions for the root system, root biomass turnover rates (yr-1), estimated by core sampling, were 1.72 (Erica) and 1.27 (Molinia). Root length production of both species, estimated by minirhizotron observations, varied significantly with observation depth. Root length turnover rate (yr-1) of both species did not vary significantly with observation depth and averaged 0.92 in Erica and 2.28 in Molinia. Reasons are given for the discrepancy between the results of the two types of turnover measurements. The data suggest that the replacement of Erica by Molinia in a wet heathland, which occurs when nutrient availability increases, leads to an increased flow of carbon and nutrients into the soil-system. Therefore, there may be a positive feedback between dominance of Molinia and nutrient availability. | {
"pile_set_name": "PubMed Abstracts"
} |
A patient-centred approach to sexuality in the face of life-limiting illness.
Sexuality is intrinsic to a person's sense of self and can be an intimate form of communication that helps relieve suffering and lessens the threat to personhood in the face of life-limiting illness. Health professionals struggle to accept that people with life-limiting illness, especially older people, continue to be sexual beings. People facing life-limiting illness may appreciate the opportunity to discuss issues of sexuality and intimacy with a trusted health professional. Practical strategies to assist health professionals to communicate effectively about sexuality and intimacy include creating a conducive atmosphere, initiating the topic, using open-ended questions and a non-judgmental approach, and avoiding medical jargon. | {
"pile_set_name": "PubMed Abstracts"
} |
Pharmacokinetics of a new inotropic catecholamine in dog plasma using solid phase extraction technology.
The pharmacokinetics of a new inotropic catecholamine, N-[2-(3,4-dihydroxyphenyl)-ethyl]-1-methyl-3-(3-carbomylphenyl)-pr opylamine HCL (KM-13), was studied following i.v. injection of 50 and 100 micrograms/kg doses to dogs. KM-13 was extracted from plasma using Bond-Elut CN columns and quantitated by HPLC with electro-chemical detection. The plasma concentration--time profile of KM-13 following an i.v. bolus was best fitted with a bi-exponential equation and the terminal elimination phase had a half life of about 20 min. The analytical method, with a limit of sensitivity of 2 ng/ml, would appear to have general applicability in studying the pharmacokinetics of synthetic catecholamines. | {
"pile_set_name": "PubMed Abstracts"
} |
X-ray structure of the magnesium(II)-pyrophosphate complex of the truncated head of Dictyostelium discoideum myosin to 2.7 A resolution.
The structure of the magnesium pyrophosphate complex of the truncated head of Dictyostelium myosin has been determined by molecular replacement at 2.7 A resolution and refined to a crystallographic R-factor of 16.0%. The crystals belong to the orthorhombic space group P2(1)2(1)2, where a = 105.2 A, b = 182.1 A, and c = 54.5 A. The conformation of the protein around the magnesium pyrophosphate is very similar to that seen when magnesium ADP-beryllium fluoride binds in the active site. The latter complex mimics the binding of ATP prior to hydrolysis. The pyrophosphate molecule occupies the beta- and gamma-phosphate sites, where the two phosphorus atoms are in the same positions as the beta-phosphate and the BeFx moiety of the beryllium fluoride-trapped ADP. The surrounding active site residues are almost perfectly superimposable in the two structures and the hydrogen-bonding interactions that the PPi makes with the protein are essentially identical. The similarity between the MgPPi and MgADP.BeFx complex with S1Dc suggests that the conformational change, which occurs when ATP binds to actomyosin and which reduces the affinity of myosin for actin, is caused by the binding of the gamma- and beta-phosphate groups of the nucleotide. This then implies that the role of the remainder of the substrate is to increase the binding affinity for myosin and thus to drive the equilibrium toward dissociation of myosin from actin. | {
"pile_set_name": "PubMed Abstracts"
} |
pH-dependent fluoride inhibition of catalase activity.
The inhibitory effects of fluoride on several catalases were examined over a range of pH conditions. Preparations of bovine-liver catalase were sensitive to fluoride under acidic conditions. Catalase activity associated with whole-cell preparations of Actinomyces viscosus NP 311A remained relatively constant between pH 3.0 and 8.0 and was inhibited by fluoride in a pH-dependent manner. Fluoride was also observed to enhance hydrogen peroxide killing of A. viscosus NP 311A under acidic pH conditions. Results suggest that some catalase enzymes, including those associated with common plaque bacteria, may be inhibited by fluoride in a pH-dependent manner. | {
"pile_set_name": "PubMed Abstracts"
} |
Estrogenic activity of osthole and imperatorin in MCF-7 cells and their osteoblastic effects in Saos-2 cells.
There is an increasing interest in phytoestrogens due to their potential medical usage in hormone replacement therapy (HRT). The present study was designed to investigate the in vitro effects of estrogen-like activities of two widespread coumarins, osthole and imperatorin, using the MCF-7 cell proliferation assay and their alkaline phosphatase (ALP) activities in osteoblasts Saos-2 cells. The two compounds were found to strongly stimulate the proliferation of MCF-7 cells. The estrogen receptor-regulated ERα, progesterone receptor (PR) and PS2 mRNA levels were increased by treatment with osthole and imperatorin. All these effects were significantly inhibited by the specific estrogen receptor antagonist ICI182, 780. Cell cycle analysis revealed that their proliferation stimulatory effect was associated with a marked increase in the number of MCF-7 cells in S phase, which was similar to that observed with estradiol. It was also observed that they significantly increased ALP activity, which was reversed by ICI182,780. These results suggested that osthole and imperatorin could stimulate osteoblastic activity by displaying estrogenic properties or through the ER pathway. In conclusion, osthole and imperatorin may represent new pharmacological tools for the treatment of osteoporosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Preliminary Results Concerning the Influence of Human Kisspeptin on LH Secretion in Prussian Carp (Carassius gibelio) Females at the Stage of Ovarian Recrudescence and Spawning Season.
The aim of the experiments was to evaluate the influence of human kisspeptin on LH secretion of Prussian carp (Carassius gibelio) females during ovarian recrudescence and spawning season. For the experiments, human kisspeptin KISS1 (0.1 mg kg(-1) of body weight--b.w.), GnRH analogue (Des Gly(10), D-Ala(6)) GnRH-A (20 µg kg(-1) b.w.) and dopamine antagonist (pimozide) (5 mg kg(-1) b.w.) were used alone or in combinations. At 3, 6, 12, 24 hours after injection(s) blood samples were collected from all fish. LH levels were measured in plasma with the use of the ELISA method. KISS1 did not show any significant effects on spontaneous LH secretion in both tested seasons. At 12 hours sampling time (both stages of gonad maturity) a combination of tested compounds (GnRH-A+KISS1) significantly increased LH release in comparison with the control. In the stage of gonad recrudescence KISS1 significantly increased LH secretion evoked by pimozide at 24 hours. A combination of three components: KISS1, GnRH-A, and pimozide significantly decreased LH secretion in comparison to LH secretion evoked by GnRH-A and pimozide during stage of gonad recrudescence. These results suggest that kisspeptin is involved in seasonal control of reproduction in Prussian carp. The possible interaction of kisspeptin and the dopaminergic system is also discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Anthocyanin from strawberry (Fragaria ananassa) with the novel aglycone, 5-carboxypyranopelargonidin.
An anthocyanin, 1, with the novel 4-substituted aglycone, 5-carboxypyranopelargonidin, was isolated in small amounts from the acidified, methanolic extract of strawberries, Fragaria ananassa Duch., by preparative HPLC after purification by partition against ethyl acetate, Amberlite XAD-7 and Sephadex LH-20 column chromatography. It was identified mainly by 2D NMR spectroscopy and electrospray LC-MS as the 3-O-beta-glucopyranoside of 5-carboxy-2-(4-hydroxyphenyl)-3,8-dihydroxy-pyrano[4,3,2-de]-1-benzopyrylium, an anthocyanidin which is homologous to 5-carboxypyranomalvidin (vitisidin A) reported in red wines and 5-carboxypyranocyanidin recently isolated from red onions. By comparison of UV-Vis absorption spectra, 1 showed in contrast to 2, pelargonidin 3-O-beta-glucopyranoside, a local absorption peak around 360 nm, a hypsochromic shift (8 nm) of the visible absorption maximum, and lack of a distinct UV absorption peak around 280 nm. The similarities between the absorption spectra of 1 in various acidic and neutral buffer solutions implied restricted formation of the instable colourless equilibrium forms, which are typical for most anthocyanins in weakly acidic solutions. The molar absorptivity (epsilon) of 1 varied little with pH contrary to similar values of for instance the major anthocyanin in strawberry, 2. However, 2 revealed higher epsilon-values than 1 at all pH values except 5.1. At pH 5.1, the epsilon-value of 1 (6250) was nearly four times the corresponding value of 2 (1720), which showed the potential of 5-carboxypyranopelargonidin derivatives as colorants in solutions with pH around 5. The colours of 1 and 2 in buffered solutions with pH 1.1 and pH 6.9 have been described by the CIELAB coordinates h(ab) (hue angle), C* (chroma), and L* (lightness). | {
"pile_set_name": "PubMed Abstracts"
} |
Atypical hemolytic uremic syndrome associated with mutations in complement regulator genes.
In the last 10 years the knowledge of the pathophysiology of atypical hemolytic uremic syndrome (aHUS) has substantially increased. Nevertheless, aHUS remains a severe disorder, in which early recognition of symptoms remains a key issue. The landmark discovery of genetic abnormalities in complement regulatory genes in most patients gave us new insights into the influence of each abnormality on the disease outcome and opened new perspectives for patient management. This allows a potentially more tailored approach in treating aHUS patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Rehabilitation of the dysfunctional bladder in children: method and 3-year followup.
A rehabilitation program has been developed for children with functional, nonneurogenic bladder disturbance. The basis for the program is a bladder regimen supplemented by biofeedback training if needed. Results in the first 70 children (64 girls and 6 boys) are presented. After 1 and 3 years 36 and 53 children, respectively, had completely normalized voiding patterns, that is they were continent, had no urgency, voided 3 to 6 times a day and emptied the bladder completely in 1 portion with a normal flow rate. The training program is applicable in children with varying urodynamic diagnoses and it has been used in children as young as 4 years old. | {
"pile_set_name": "PubMed Abstracts"
} |
Severe antibody-mediated human insulin resistance: successful treatment with the insulin analog lispro. A case report.
To evaluate the efficacy of the insulin analog lispro (Lys B28, Pro B29) in severe insulin resistance caused by human insulin antibodies. A 27-year-old man with a history of diabetes treated with human insulin for 3 years developed severe immunological insulin resistance caused by human insulin antibodies. Throughout follow-up (12 months) the insulin analog lispro was administered with an infusion pump as the only insulin therapy. The insulin dose decreased from an average of 300 U/day to 58 U/day, HbA1c decreased from 12.6 to 7.4%, and human insulin antibodies decreased from 8,057 to 1,860 nU/ml. Hypoglycemic episodes during early morning disappeared. The insulin analog lispro might be suitable for the treatment of diabetic patients with substantially increased insulin antibody levels Apparently, the structural difference between the lispro and human insulin molecules prevented lispro from binding to the human insulin antibodies in this patient and consequently was nonimmunogenic. | {
"pile_set_name": "PubMed Abstracts"
} |
Weights of brain, heart, liver, kidneys, and spleen in healthy and apparently healthy adult Danish subjects.
Based on a forensic material of 1,598 autopsies of Danish adults (1,086 males, 512 females ≥ 16 years of age), who prior to death were healthy or apparently healthy based on clinical evidence, the weights of brain, heart, liver, kidneys, and spleen were registered. The variability of organ weights was estimated. Relationships between organ weights and body size, and among organ weights were also evaluated. Males had larger organ weights than females. When organ weights were based on the same estimated fat free mass, interesting differences between the sexes were observed: weights of the heart and brain were smaller in females, but weights of the kidney were the same; weights of the liver were consistently larger in females than in males. Useful comparisons of the data with previous studies were impossible because of differences in the criteria of health and of insufficient numbers. © 1993 Wiley-Liss, Inc. | {
"pile_set_name": "PubMed Abstracts"
} |
[The pentoxifylline, a corticosteroid sparing in the treatment of sarcoidosis: A case report].
The pentoxifylline seems to have some effects on immune cells by inhibiting tumor necrosis factor alpha (TNFα). Its role as a sparing corticosteroids in the treatment of sarcoidosis remains to be defined. We present the case of a patient with sarcoidosis corticodependent despite the use of azathioprine. It was finally improved clinically, functionally and by a thoracic computed tomography with addition of pentoxifylline. When the tolerance of the pentoxifylline is good and there is not a bleeding risk, the benefit-risk in the long term might be interesting in some patients with sarcoidosis corticodependent. | {
"pile_set_name": "PubMed Abstracts"
} |
The impact of dendritic cell-tumor fusion cells on cancer vaccines - past progress and future strategies.
Dendritic cells (DCs) are potent antigen-presenting cells that can be used in cancer vaccines. Thus, various strategies have been developed to deliver tumor-associated antigens via DCs. One strategy includes administering DC-tumor fusion cells (DC-tumor FCs) to induce antitumor immune responses in cancer patients. However, clinical trials using this strategy have fallen short of expectations. Several factors might limit the efficacy of these anticancer vaccines. To induce efficient antitumor immune responses and enhance potential clinical benefits, DC-tumor FC-based cancer vaccines require manipulations that improve immunogenicity for both DCs and whole tumor cells. This review addresses recent progress in improving clinical outcomes using DC-tumor FC-based cancer vaccines. | {
"pile_set_name": "PubMed Abstracts"
} |
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