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Terms modified by Failed Selected AbstractsImproving service delivery by evaluation of the referral pattern and capacity in a clinical genetics setting,,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2009Emma McCann§ Abstract Quality improvement in specialist services such as clinical genetics is challenging largely due to the complexity of the service and the difficulty in obtaining accurate, reproducible, and measurable data. The objectives were to evaluate the pattern of referrals to the All Wales Medical Genetics Service (AWMGS) North Wales Genetics team based in three separate hospitals, define the capacity of the team and implement change to improve equity, timeliness and efficiency of care delivery to patients. The methodology required collating the monthly referral rates retrospectively for each center over a 2.5-year period and plotting on statistical process control charts. Process mapping of the referral process in each center was undertaken, differences documented and a common pathway implemented. "Did not attend" and "time to first appointment" rates were also measured in one center. PDSA methodology was used to implement "patient focused booking." The results show that the range for referral rates in any given month for each center was 3,33 referrals. The range for referral rate for the whole team was 18,64 per month. Since January 2004 the average number of monthly referrals to the North Wales service has increased by 50%. The potential range in monthly referrals varies between centers and the range of the variability has also increased also in two out of the three centers. Introduction of Patient Focused Booking reduced the "Failed to Attend" rate and 100% of patients were offered a choice of appointments. In addition 100% had a first face-to-face contact within 6 weeks if they chose. The measurement of improvement involved firstly introducing a series of continuous measures to provide a baseline for the process prior to the implementation of any changes and secondly to indicate the impact of the changes following implementation. The measures implemented included process (referrals numbers, percentage of patients offered a choice of appointments), outcome (percentage of patients seen within 6 weeks and the percentage failing to attend), and balancing measures (percentage declining the service or failing to respond). It was concluded that general tools of quality improvement can be used to good effect within specialist services. Good processes and accurate, reproducible and measurable data are essential. Small changes can have a major impact both on the quality of the service offered and the ability to deliver the service. © 2009 Wiley-Liss, Inc. [source] Differential effects of stress and amphetamine administration on Fos-like protein expression in corticotropin releasing factor-neurons of the rat brainDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2007David Rotllant Abstract Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Clinical and diagnostic significance of blood in cervical smearsDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2003Mathilde E. Boon M.D., Ph.D. Abstract A heavy admixture of blood in cervical smears can be problematic for the screener, as the presence of blood can influence the staining quality of the cancer cell nuclei. However, it might also be a blessing in disguise. A retrospective study of 40 clinically important smears, 34 originally signed out as negative for squamous cell carcinoma of the cervix and 6 smears as unsatisfactory, was carried out in comparison with 100 smears from healthy women. Sample parameters were analyzed by macroscopy and neural network scanning. Differences between the two study groups were measured by Pearson's ,2 test. Of the 40 study cases, one case featured insufficient material, while 16 cases (40%) could confidently be classified as malignant or negative for malignancy. The most important macroscopic parameter of the smears was an admixture of blood. This background feature was also highlighted by the NNS system. Angiogenesis was visualized by the expression of CD34 in many sampled capillary fragments included in the smears. In conclusion, blood in cervical smears may have clinical and diagnostic significance. The rate of "failed smears" in routine cervical screening might thus by CD34 be considerably decreased. Diagn. Cytopathol. 2003;28:181,185. © 2003 Wiley-Liss, Inc. [source] Mechanistic studies of blood pressure in rats treated with a series of cholesteryl ester transfer protein inhibitors,DRUG DEVELOPMENT RESEARCH, Issue 1 2009Michael DePasquale Abstract ILLUMINATE, the Phase 3 clinical trial of morbidity and mortality (M&M) with the cholesteryl ester transfer protein inhibitor (CETPi), torcetrapib (CP-529,414), was terminated in December 2006 due to an imbalance in all cause mortality. The underlying cause of the M&M remains undetermined. While torcetrapib produced dose-related increases in blood pressure in clinical trials, the mechanism of the increase in blood pressure is also undetermined. The pressor effects of torcetrapib and structurally related compounds were studied in several pathways involved in blood pressure control. Studies were conducted in rats treated with a series of structurally related molecules (CP-529,414, CP-532,623, PF-868,348, CP-746,281, CP-792,485, PF-868,343, and CE-308,958). CP-529,414, CP-532,623, CP-868,343, and CP-792,485 are potent CETP inhibitors; PF-868,348 is weakly potent and CP-746,281 and CE-308,958 are CETP-inactive. Changes in blood pressure were determined in conscious animals in conjunction with pharmacologic blockade of numerous pressor agents/pathways. Torcetrapib and CP-532,623 increased blood pressure following both chronic PO and acute IV administration. The CETP-inactive enantiomer of CP-532,623, CP-746,281 failed to raise blood pressure. PF-868,348, a structural analogue with ,50-fold lower CETPi activity also displayed pressor activity. Blockade of adrenergic, cholinergic, angiotensin, endothelin, NOS, Rho kinase, and thromboxane pathways failed to attenuate the pressor response. These data demonstrate that the blood pressure activity seen with torcetrapib can be dissociated from CETP inhibitor pharmacology and numerous pharmacology pathways can be discounted in the attempt to understand the molecular basis of the pressor pharmacology. Drug Dev Res 70:2009 © 2009 Wiley-Liss, Inc. [source] Adenosine downregulates cytokine-induced expression of intercellular adhesion molecule-1 on rheumatoid synovial fibroblasts independently of adenosine receptor signalingDRUG DEVELOPMENT RESEARCH, Issue 4 2003Takashi Nakazawa Abstract Adhesion of fibroblast-like synoviocytes (FLSs) to T cells through the interaction of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). We therefore used flow cytometry and quantitative polymerase chain reaction (PCR) to examine the effect of adenosine and its derivatives on expression of ICAM-1 induced by tumor necrosis factor-alpha and interferon-gamma in primary rheumatoid FLSs (RA-FLSs) and E11 cells, an RA-FLS line. Exposing cells to adenosine (5,500 µM) for 24 h in the presence of coformycin, an adenosine deaminase inhibitor, concentration-dependently inhibited cytokine-induced transcription of ICAM-1 mRNA, as well as subsequent surface expression of the protein. Although transcription of all four adenosine receptor isoforms has been detected in FLSs, neither the A1 receptor agonist R-PIA, the A2A receptor agonist CGS21680 nor the A3 agonist Cl-IB-MECA had any effect on cytokine-induced ICAM-1 expression. Conversely, A1/A2 receptor antagonist xanthine amine congener and A2A antagonist ZM240385 both failed to suppress the effect of adenosine. Adenosine appears to inhibit cytokine-induced ICAM-1 expression in FLSs independently of adenosine receptor-mediated signaling. By contrast, the effect of adenosine was neutralized by nitrobenzylmercaptopurin, a nucleoside transporter inhibitor, or by ABT702, an adenosine kinase inhibitor. This suggests that adenosine taken up via the nucleoside transporter is phosphorylated by adenosine kinase, and the resultant phospho-adenosine interferes with the ICAM-1 transcription and cell surface expression. Downregulation of T cell,FLS interaction by adenosine may thus represent a novel approach to the treatment of RA. Drug Dev. Res. 58:368,376, 2003. © 2003 Wiley-Liss, Inc. [source] Assessment of shallow landslide susceptibility by means of multivariate statistical techniquesEARTH SURFACE PROCESSES AND LANDFORMS, Issue 12 2001Cristina Baeza Abstract Several multivariate statistical analyses have been performed to identify the most influential geological and geomorphological parameters on shallow landsliding and to quantify their relative contribution. A data set was first prepared including more than 30 attributes of 230 failed and unfailed slopes. The performance of principal component analysis, t-test and one-way test, allowed a preliminary selection of the most significant variables, which were used as input variables for the discriminant analysis. The function obtained has classified successfully 88·5 per cent of the overall slope population and 95·6 per cent of the failed slopes. Slope gradient, watershed area and land-use appeared as the most powerful discriminant factors. A landslide susceptibility map, based on the scores of the discriminant function, has been prepared for Ensija range in the Eastern Pyrenees. An index of relative landslide density shows that the results of the map are consistent. Copyright © 2001 John Wiley & Sons, Ltd. [source] Does progressive stage transition mean getting better?ADDICTION, Issue 10 2007A test of the Transtheoretical Model in alcoholism recovery ABSTRACT Aims To test two central assumptions of stage movement in the Transtheoretical Model (TTM) vis-à-vis alcoholism recovery: (assumption 1) individuals making a forward transition to the action-oriented stages (i.e. preparation/action) will manifest relatively greater drinking improvements than their counterparts remaining in the pre-action stages (i.e. pre-contemplation, contemplation); and (assumption 2) individuals remaining in the pre-action stages across time will not demonstrate clinically relevant improvement in drinking outcomes. Design and setting Secondary data analyses of data from Project MATCH, a large multi-site alcoholism treatment-matching study. Measurements At baseline and 3 months post-treatment, the following variables were measured: stage-of-change (based on the University of Rhode Island Change Assessment measure and the most recent stage assignment algorithm), drinks per drinking day (DDD) and percentage days abstinent (PDA). Findings Six of the eight tests of assumptions 1 and 2 failed to support the basic tenets of the TTM. Our study demonstrated that individuals making a progressive stage transition to the action-oriented stages (i.e. preparation/action) do not necessarily manifest greater improvements in drinking-related behavior than individuals remaining in the pre-action stages (i.e. pre-contemplation, contemplation), and that individuals remaining in the pre-action stages over time actually do manifest statistically significant and clinically important improvements in drinking-related behavior. Conclusions Our findings challenge not only the criterion validity associated with stage movement in the TTM account of alcoholism recovery, but also recent TTM-based substance abuse treatment approaches which systematically promote forward stage transition as a primary clinical goal and marker of therapeutic success. [source] Specific Ca2+ Fluorescent Sensor: Signaling by Conformationally Induced PET Suppression in a Bichromophoric AcridinedioneEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 34 2009Pichandi Ashokkumar Abstract A series of acridinedione-based bichromophoric podand systems 1a,c were synthesized and characterized. Among these, bichromophore 1c shows specific binding of Ca2+ in the presence of other biologically important metal ions like Na+, K+, Mg2+, and Zn2+. The selective complexation was proved by steady-state emission, time-resolved emission, and 1H NMR titration. Signaling of the binding event was achieved by Ca2+ -induced folding of the bichromophore, resulting in PET suppression in the acridinedione chromophore. Involvement of a PET process in the optical signaling was confirmed by comparing bichromophores 1a,c with non-PET compound 2 and monochromophore model compound 3. Non-PET compound 2 failed to give optical response upon Ca2+ binding as a result of the absence of a PET process in the Ca2+ -bound complex. Monochromophore 3 shows a similar optical response, which is the same as that in 1c. Titration of the metal-ion-bound complex of 1c with EDTA released the metal ion from the complex, thereby regaining the original photophysical properties of the bichromophore.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Response of the flora and macroinvertebrate fauna of a chalk stream site to changes in managementFRESHWATER BIOLOGY, Issue 5 2003J. F. Wright SUMMARY 1. Temporal changes in a series of habitats and their macroinvertebrate assemblages were examined on a 50-m section of a chalk stream in Berkshire, England between June 1975,79 and June 1997,2001. 2. The site was part of a trout fishery in 1975,79, when river management included instream weed cutting together with control of bankside trees and riparian vegetation. Management ceased in the 1980s and by 1997,2001, the site was heavily shaded by trees and riparian vegetation. 3. The mean area of instream macrophytes decreased by 50% between the first and second sampling period. In contrast, gravel and silt increased and invading marginal vegetation formed a new habitat. 4. Changes in macroinvertebrate family richness between sampling periods were scale dependant. Although there were, on average, significantly more families in individual replicates in 1975,79 than in 1997,2001, total family richness for the site in each year did not differ significantly between sampling periods. 5. Sixty families of macroinvertebrates were recorded during the study, 50 in both sampling periods, 53 in 1975,79 and 57 in 1997,2001. This small increase in site family richness may be due to the invading marginal plants. 6. Total macroinvertebrate abundance was significantly lower in the second sampling period. A major drought in 1976 resulted in significantly higher densities of macroinvertebrates, partly through the exploitation of epiphytic diatoms by chironomid larvae. A drought in 1997 failed to elicit a similar response because of the limited macrophytes and diatoms under heavy shading by trees and marginal vegetation. 7. Significant increases in important shredders and decreases in some scrapers between the early and later sampling years largely reflected changes in available food resources. 8. Whereas macroinvertebrate family richness has been conserved under the recent ,no management' regime, the site is now less attractive as a fishery because of poor access and lower densities of some macroinvertebrates taken by brown trout. [source] Further experience with botox injection for tracheoesophageal speech failureHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2001Jan S. Lewin PhD Abstract Background Some patients fail to acquire tracheoesophageal (TE) speech after laryngectomy because of pharyngeal constrictor hypertonicity. Botox injection relieves hypertonicity, but there are little objective data regarding outcomes, duration of effect, and reinjection rates. Methods Hypertonicity was identified by means of insufflation testing and confirmed videofluoroscopically in 23 unsuccessful TE speakers. Each patient received an EMG-guided Botox injection. Additional injections were offered if the first injection failed to produce fluent speech. Results Overall, 20 of 23 patients (87%) achieved fluent TE speech production after Botox injections; 5 after additional injections. Two patients declined further intervention, and 1 failed to achieve fluent TE speech production even after 3 Botox injections. The longest sustained effect was 37 months, the shortest was 5 months for 1 patient who required reinjection of Botox to maintain her TE speech production. Conclusions Botox injection relieves constrictor hypertonicity in selected cases of TE speech failure with little need for reinjection to maintain long-term speech success. © 2001 John Wiley & Sons, Inc. Head Neck 23: 456,460 2001. [source] Adult hepatitis B vaccination using a novel triple antigen recombinant vaccineHEPATOLOGY, Issue 2 2001Michael D. Young Present hepatitis B vaccines use multidose prolonged regimens, which even healthcare workers at risk do not always complete. Moreover, when vaccination is completed there remain some who fail to achieve adequate protection. The protection of adults at risk could be improved if there were a more potent vaccine and/or a shorter vaccination regimen available. Vaccine-naive adults were randomized to vaccination with either Engerix-B (SmithKline Biologicals, Rixensart, Belgium) or a novel triple antigen (S, pre-S1, and pre-S2) recombinant vaccine (Hepacare; Medeva Pharma Plc, Speke, UK). The primary efficacy parameter was the degree of seroprotection 6 or 7 months (26 ± 2 weeks) after beginning vaccination. A total of 304 adults entered the study. Of these, 16 failed to complete the study (9 on Hepacare and 7 on Engerix-B). With the Engerix-B standard (0, 1, 6) regimen, 88% of subjects were protected by month 7, whereas with the triple antigen vaccine a 2-dose regimen (0, 1) provided equivalent protection (91%) within 6 months and a 3-dose (0, 1, 6) regimen was significantly superior (98% seroprotected by 7 months after starting vaccination P < .001). With adults at risk for a suboptimal response (i.e., older adults, the obese, men, and smokers) the triple antigen vaccine produced a greater degree of protection. The vaccines had similar safety profiles. Both vaccines were well tolerated. In healthy normal adults, a triple antigen hepatitis B vaccine containing S and pre-S antigens produced an enhanced immunologic response and was as effective as a 2- and 3-dose regimen. [source] Distinction between coeliac disease and refractory sprue: a simple immunohistochemical methodHISTOPATHOLOGY, Issue 1 2000N Patey-Mariaud de Serre Aims We recently showed that refractory sprue is distinct from coeliac disease, the former being characterized by abnormal intraepithelial T-lymphocytes expressing a cytoplasmic CD3 chain (CD3c), lacking CD3 and CD8 surface expression, and showing TCR, gene rearrangements. To take advantage of the abnormal phenotype of CD3c + CD8 , intraepithelial lymphocytes (IEL) in refractory sprue we developed a simple method to distinguish coeliac disease from refractory sprue. Methods and results Comparative immunohistochemical studies using anti-CD3 and anti-CD8 antibodies were applied on paraffin-embedded and frozen biopsy specimens in refractory sprue (n = 6), coeliac disease (n = 10), healthy controls (n = 5) and suspected refractory sprue (n = 6). Comparable results were obtained on fixed and frozen biopsy specimens. In four of the six patients with suspected refractory sprue, abnormal CD3c + CD8 , IEL and TCR, gene rearrangements were found, as in refractory sprue; the remaining two patients had normal (CD3 + CD8 +) IEL and no TCR, gene rearrangements. Both patients had coeliac disease, as one failed to comply with a gluten-free diet, while the other was a slow responder. Conclusion This simplified immunostaining method using anti-CD3 and anti-CD8 antibodies on paraffin sections can distinguish active coeliac disease from refractory sprue and should prove useful in clinical practice. [source] Mechanism of metabolic activation and DNA adduct formation by the human carcinogen diethylstilbestrol: The defining link to natural estrogensINTERNATIONAL JOURNAL OF CANCER, Issue 6 2009Muhammad Saeed Abstract Diethylstilbestrol (DES) is a human carcinogen, based on sufficient epidemiological evidence. DES is mainly metabolized to its catechol, 3,-hydroxyDES (3,-OH-DES), which can further oxidize to DES-3,,4,-quinone (DES-3,,4,-Q). Similarly to estradiol-3,4-quinone, the reaction of DES-3,,4,-Q with DNA would form the depurinating 3,-OH-DES-6,-N3Ade and 3,-OH-DES-6,-N7Gua adducts. To prove this hypothesis, synthesis of DES-3,,4,-Q by oxidation of 3,-OH-DES with Ag2O was tried; this failed due to instantaneous formation of a spiro -quinone. Oxidation of 3,-OH-DES by lactoperoxidase or tyrosinase in the presence of DNA led to the formation of 3,-OH-DES-6,-N3Ade and 3,-OH-DES-6,-N7Gua adducts. These adducts were tentatively identified by LC-MS/MS as 3,-OH-DES-6,-N3Ade, m/z = 418 [M+H]+, and 3,-OH-DES-6,-N7Gua, m/z = 434 [M+H]+. Demonstration of their structures derived from their oxidation by MnO2 to the DES quinone adducts and subsequent tautomerization to the dienestrol (DIES) catechol adducts, which are identical to the standard 3,-OH-DIES-6,-N3Ade, m/z = 416 [M+H]+, and 3,-OH-DIES-6,-N7Gua, m/z = 432 [M+H]+, adducts. The reaction of DIES-3,,4,-Q or lactoperoxidase-activated 3,-OH-DIES with DNA did not produce any depurinating adducts, due to the dienic chain being perpendicular to the phenyl planes, which impedes the intercalation of DIES into the DNA. Enzymic oxidation of 3,-OH-DES suggests that the catechol of DES intercalates into DNA and is then oxidized to its quinone to yield N3Ade and N7Gua adducts. These results suggest that the common denominator of tumor initiation by the synthetic estrogen DES and the natural estrogen estradiol is formation of their catechol quinones, which react with DNA to afford the depurinating N3Ade and N7Gua adducts. © 2008 Wiley-Liss, Inc. [source] Growth of pure cultures of Verocytotoxin-producing Escherichia coli in a range of enrichment mediaJOURNAL OF APPLIED MICROBIOLOGY, Issue 5 2008C.L. Baylis Abstract Aims:, This study compared the growth of different strains of Verocytotoxin-producing Escherichia coli (VTEC) in a range of selective enrichment media. Methods and Results:, Turbidometric and impedance methods were used to determine the growth of VTEC in pure culture in different enrichment media. Ten strains failed to grow in buffered peptone water + vancomycin, cefsulodin, cefixime at 42°C and some failed to grow, or grew poorly in E. coli (EC) medium supplemented with 20 mg l,1 novobiocin and modified EC supplemented with 20 mg l,1 novobiocin at 37°C and 42°C. Individual VTEC strains were sensitive to the selective agents in some media. Statistical analysis of the conductance detection times of 10 strains showed no overall effect of temperature alone (P = 0·66) but there were significant (P < 0·001) effects as a result of the combination of medium and temperature and these two factors were influenced by strain. Conclusions:, Growth of VTEC during enrichment is dependent on different factors alone or in combination. These include medium type, presence of certain selective agents or antibiotics, incubation temperature and the initial population of VTEC. Sensitivity to these conditions can be strain related. Significance and Impact of the Study:, This study highlighted differences in the ability of some enrichment media to support the growth of VTEC, making them unsuitable for the isolation of VTEC, especially low numbers of non-O157 strains. [source] Human monocyte response to retrieved polymethylmethacrylate particlesJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 3 2002Masatsugu Miyaguchi Abstract The purpose of this study was to compare retrieved polymethylmethacrylate (PMMA) particles from failed total hip arthroplasties in terms of size, shape, and the response of human monocytes with commercially available particles. PMMA particles were isolated from peri-implant tissues of five failed cemented total hip arthroplasties using tissue digestion and a sucrose density gradient technique. Prepolymerized cement powder and those from which barium sulfate had been removed were examined for comparison. After exposure of peripheral human monocytes to PMMA particles, tumor necrosis factor-, and interleukin-6 in medium were measured by using enzyme-linked immunosorbent assays. Image analysis revealed that retrieved particles were larger (retrieved: 1.24 ,m; prepolymerized cement powder: 0.83 ,m; barium sulfate-free powder: 0.87 ,m) and were more irregular in shape and rougher than commercially available particles. Cytokine release was increased by all PMMA particle species. However, commercially available PMMA particles stimulated the release of necrosis factor-, and interleukin-6 more strongly than did retrieved particles at very high doses. The observed difference in monocyte response might be due to the volume of the challenged particles. Another possible reason for the difference might be alteration of the surface chemistry of particles in situ and the difference in surface morphology between them. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 331,337, 2002 [source] Candida dubliniensis screening using the germ tube test in clinical yeast isolates and prevalence of C. dubliniensis in KoreaJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2010Tae-Hyoung Kim Abstract The aim of this study was to screen for C. dubliniensis using the germ tube test with human pooled serum (HPS) in clinical isolates and investigate the prevalence of C. dubliniensis in Korea. Among 1,854 yeast strains isolated, 1,404 strains of C. albicans (on the basis of positive results of the germ tube test) and 192 germ tube-negative yeast strains were examined. All 1,596 clinical isolates were examined using the germ tube test with HPS, the differential temperature, and NaCl tolerance test. Only 81 isolates that did not grow at 45°C nor on Sabouraud 6.5% NaCl broth were selected and tested using the VITEK 2 ID-YSTsystem and the multiplex-PCR assay for the study. The two strains, C. dubliniensis ATCC MYA-646 and KCTC 17427 failed to produce germ tubes in HPS but produced them in fresh rabbit serum (FRS) and fetal bovine serum (FBS). No C. dubliniensis was found in this study population. The results of this study suggest that the germ tube test with HPS in combination with FRS or FBS can be used for discriminating between C. albicans and C. dubliniensis strains and that the prevalence of C. dubliniensis appears to be extremely low in Korea. J. Clin. Lab. Anal. 24:145,148, 2010. © 2010 Wiley-Liss, Inc. [source] The chemical and pharmaceutical equivalence of sulphadoxine/pyrimethamine tablets sold on the Tanzanian marketJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2005Y. Hebron BPharm MSc Summary This study investigated chemical and pharmaceutical equivalence of 11 brands of pyrimethamine,sulphadoxine combination tablets sold on the Tanzanian market. Physical and chemical tests were performed for all the 11 brands. These tests included hardness test, friability, disintegration, dissolution, weight uniformity and assay for the active components. All the brands passed all the quality specifications of the United States Pharmacopoeia (USP) and British Pharmacopoeia (BP) in terms of hardness, friability, disintegration, assay and dissolution test, except for three brands that failed the hardness, disintegration or friability tests. One brand failed both the hardness and disintegration test; one failed the hardness test, whereas another one failed the friability test. The percentage content of pyrimethamine in the brands was in the range of 91·04,100·20% whereas that of sulphadoxine ranged from 91·53% to 99·88%. There were no major differences between the different brands of tablets containing pyrimethamine and sulphadoxine and the innovator product (Fansidar®), and all brands were physically and chemically equivalent. The results indicate that the post-market surveillance and registration process in Tanzania is having an impact on product quality as there was no brand which could be considered of very poor quality. Impurity profiling of all the locally produced brands indicated that they all contained the same sulphadoxine impurity, which was absent in the innovator product, suggesting a common source of generic raw material. [source] Breeding biology of Eared Quetzals in the Sierra Madre Occidental, MexicoJOURNAL OF FIELD ORNITHOLOGY, Issue 1 2008José I. González-Rojas ABSTRACT Eared Quetzals (Euptilotis neoxenus), a threatened species, are one of the least studied trogons in Mexico. We monitored 29 Eared Quetzal nests in the Chihuahuan portion of the Sierra Madre Occidental from 1998 to 2003. All nests were in tree cavities, and the mean tree and nest cavity heights (N= 14) were 16.9 ± 7.8 m and 11.4 ± 4.1 m, respectively. The mean clutch size was 2.8 ± 0.9 eggs (N= 28), the incubation period lasted 22 d (N= 1), and nestling periods ranged from 29 to 31 d (N= 5). Both adults incubated eggs and fed nestlings. Of 80 eggs, 70 hatched (87.5%) and 67 of 70 young fledged (95.7%). Twenty-five of 29 nests (86.2%) produced at least one fledgling. One nest was predated, and two failed when nest trees fell. Higher rates of nest predation have been reported for other species of trogons. However, fewer potential predators, such as snakes and mammals, are present in the Sierra Madre than in tropical zones where most trogon species occur. In addition, antipredator behaviors, including nestlings with calls resembling a snake and nests with an unpleasant odor, may contribute to the high nesting success. The main limiting factors for Eared Quetzals in the northern Chihuahua may be competition for cavities with other secondary cavity-nesters, and the failure of nests when snags fall. SINOPSIS Euptilotis neoxenus es un ave amenazada y uno de los trogones menos estudiados de México. Monitoreamos 29 nidos en la Sierra Madre Occidental de Chihuahua durante seis años (1998,2003). Todos los nidos se encontraron en cavidades de árboles, 11 de los 14 nidos caracterizados fueron localizados en álamos (Populus tremuloides). La altura promedio de los árboles y los nidos fue de 16.9 ± 7.8 m y 11.38 ± 4.05 m, respectivamente. El tamaño de puesta fue de 2.8 ± 0.9 huevos (N= 28), el periodo de incubación duró 22 días (N= 1) y el de anidamiento 28,31 días (N= 5). Ambos adultos incubaron y alimentaron a los pollos. De 80 huevos, 70 eclosionaron (87.5%) y 67 fueron volantones (95.7%). Veinticinco de los 29 nidos (86.2%) produjeron al menos un volantón. Un nido fue depredado y dos se perdieron debido a la caída del árbol que los albergaba. Para otras especies de trogones han sido reportadas tasas de depredación más altas. Sin embargo, en la Sierra Madre Occidental existen una menor cantidad de depredadores potenciales, como serpientes y mamíferos, que en las zonas tropicales donde la mayoría de las especies de trogones está presentes. Además, comportamientos anti-depredación, incluyendo polluelos con llamados que asemejan una serpiente y nidos con un olor desagradable, podrían contribuir a un éxito reproductivo alto. Los principales factores limitantes para la productividad de esta especie son la competencia por cavidades con otras especies y la pérdida de nidos cuando los árboles en decadencia caen. [source] An intranuclear bacilliform virus associated with near extirpation of Austropotamobius pallipes Lereboullet from the Nant watershed in Ardéche, FranceJOURNAL OF FISH DISEASES, Issue 9 2002B F Edgerton White-clawed crayfish, Austropotamobius pallipes, were endemic to the Nant watershed, Ardéche, France, until they were extirpated by epizootic mortality at the beginning of the twentieth century. A. pallipes were successfully reintroduced to the Nant watershed in the middle of the twentieth century. However, epizootic mortality was observed in the Nant watershed in the summer of 2000 during which time A. pallipes was extirpated from downstream regions. Dead and moribund crayfish were again detected in several episodes in summer 2001 and by October the range of A. pallipes was reduced to the headwaters of just one of the three streams in the watershed. Water quality for the watershed in summer 2001 was appropriate for crayfish habitation. Bacteriology and mycology on A. pallipes collected during several of the mortality episodes in 2001 failed to reveal a cause. However, histopathology revealed a high occurrence of intranuclear eosinophilic inclusions in hepatopancreatocytes of A. pallipes. The nuclei were hypertrophic and contained bacilliform virions consisting of a cylindrical nucleocapsid surrounded by a trilaminar envelope. Virions in section were approximately 63 × 258 nm and nucleocapsids were approximately 52 × 225 nm. It is unclear whether the intranuclear bacilliform virus was the cause of the mortality episodes or was a contributor to a disease complex involving one or several other undetected pathogens. [source] A Comparison of Cleaning Regimes for the Effective Removal of Fingerprint Deposits from BrassJOURNAL OF FORENSIC SCIENCES, Issue 1 2010Emma Paterson Abstract:, Effective removal of fingerprint deposits is crucial for experimentation related to the corrosion of metals by fingerprint deposits. Such removal is also necessary prior to deposition of test fingerprints. The effectiveness of four regimes in removing fingerprint deposits from brass is considered. Sustained wiping of the deposit with a tissue at applied pressures of up to c. 1430 Pa or rubbing while the brass was immersed in acetone both failed to remove completely all traces of fingerprint deposits. Heating the brass to 600°C was an effective remover; however, this also oxidized the surface of the metal except where inhibited by fingerprint deposits. The most effective regime, and the only one of the four that removed all traces of deposit without affecting the properties of the metal surface, was immersion in warm soapy water while rubbing with a tissue. We propose this as the preferred method for fingerprint removal. [source] Synthesis of new fused isoquinolines via reissert compoundsJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 6 2008Christian Fuchs Reissert compounds 2 derived from isoquinoline, chloroformates and TMS-cyanide were alkylated in position 1. The resulting alkylation products 3 as well as the precursors 2 reacted with Grignard reagents affording imidazoisoquinolines 4, 5, 7 and 8 by addition to the cyano group and Grignard reduction or by twofold addition to the cyano group, respectively. In both cases the alcohol of the 2-alkoxycarbonyl moiety was eliminated by attack of the N-atom at the carbonyl carbon atom. Under acid conditions, 1-benzylated Reissert compound 3h cyclised by attack of the resulting N-acyliminium C-atom at the o -position of the benzyl ring to form tetracyclic 1,3-bridged tetrahydroisoquinolines 10 and 11. Bromocyclisation of 1-allyl-2-menthyloxycarbonyl-substituted Reissert compounds 3b, c led to tricyclic dibromo products 12, in which the menthol moiety was split off and addition to the enamine double bond occurred. A 2-menthyloxycarbonyl group in Reissert compounds 2a and 3 failed to exert an asymmetric induction in all cases. [source] Assessment of progestin-only therapy for endometriosis in macaqueJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2008G. Maginnis Abstract Background, Endometriosis is a condition where endometrium-like tissue forms lesions at ectopic sites outside the uterus. In women, oral contraceptive pills and progestins are often prescribed as therapy for early stage endometriosis. In contrast, in macaques the disease is frequently advanced at the time of diagnosis and ovariectomy is the standard therapy. However, surgery is contraindicated in many patients. A review of 15 endometriosis cases over the past 10 years at the Oregon National Primate Research Center (ONPRC) revealed that 5 failed to show improvement after ovariectomy and were subsequently euthanized. Therefore, our goal was to assess the feasibility of treating endometriosis in macaques with chronic progesterone (P) as an alternative therapy for the disease. Methods, Seven adult rhesus macaques with advanced endometriosis were identified by clinical symptoms and endometriosis was confirmed by abdominal palpation, ultrasound examination, and/or aspiration of menstrual blood from abdominal cysts. The patients were chronically treated with Silastic capsules that released 5,7 ng P /ml in blood for up to 20 months. During treatment the patients were assessed daily and scored numerically for appetite, activity, attitude, abdominal discomfort and menstruation by the Clinical Veterinary staff. The patients were then re-examined by abdominal palpation and ultrasound for the disease at the end of treatment. Results, During the first 2 weeks of treatment, endometriotic symptoms improved significantly in all the patients (P < 0.05). This was associated with a significant increase in body weight and significant reduction in abdominal discomfort and menstrual bleeding. Two of the patients gradually developed increased symptoms of the disease after 5 months of treatment. Post-treatment abdominal examination revealed that 2/5 patients continued to have an abdominal mass even though symptoms were suppressed. Conclusions, We conclude that continuous P treatment of rhesus monkeys provides therapeutic benefit to reduce symptoms of endometriosis and may provide an option for cases where ovariectomy is contraindicated. Supported by RR-00163. [source] Importance of Jugular Valve Incompetence in Contrast Transcranial Doppler Ultrasonography for the Diagnosis of Patent Foramen OvaleJOURNAL OF NEUROIMAGING, Issue 3 2003M. Akif Topçuoglu MD ABSTRACT Transcranial Doppler (TCD) ultrasound with the intravenous injection of agitated saline as contrast (cTCD) is an effective method for detecting right-to-left intracardiac and extracardiac shunt (RLS); however, the sensitivity of cTCD in the diagnosis of RLS remains slightly less than that of transesophageal echocardiography, even in patients with adequate transtemporal ultrasonic bone windows. The authors present a case with cTCD underestimating RLS because of jugular valve incompetence in a 42-year-old man presenting with an episode of transient aphasia. Three weeks after transcatheter closure of a patent foramen ovale associated with an atrial septal aneurysm, he experienced 2 episodes of amaurosis fugax. Following a negative 45-minute embolus detection study with power M-mode TCD, the patient underwent a cTCD study with monitoring of the left middle cerebral artery (MCA), the anterior cerebral artery, and the submandibular extracranial internal carotid artery. A single microbubble (MB) was detected in the left MCA in only 1 of 5 studies; the remaining runs all failed to detect an RLS. Significant MB reflux was noted in the left internal jugular vein because of jugular valve incompetence. The authors conclude that incompetence of the jugular vein valve can result in a false negative cTCD study for RLS detection. [source] Presenilin 1 mediates retinoic acid-induced differentiation of SH-SY5Y cells through facilitation of Wnt signalingJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003Kengo Uemura Abstract Presenilin 1 interacts with ,-catenin, an essential component of the Wnt signaling pathway. To elucidate the role of presenilin 1-,-catenin interaction in neuronal differentiation, we established SH-SY5Y cells stably expressing wild-type presenilin 1, P117L mutant presenilin 1, which is linked to the early-onset familial form of Alzheimer's disease, and D385A mutant presenilin 1, which has no aspartyl proteinase activity. We demonstrate that SH-SY5Y cells stably expressing D385A mutant presenilin 1 failed to differentiate in response to retinoic acid treatment. Retinoic acid caused an increase in nuclear ,-catenin levels in SH-SY5Y cells, which was followed by an increase in cyclin D1 protein levels. Abnormal cellular accumulation of ,-catenin was observed in D385A mutant transfected cells, whereas nuclear ,-catenin and cellular cyclin D1 levels failed to increase. Conversely, SH-SY5Y cells expressing the P117L mutant differentiated normally and showed increased nuclear ,-catenin and cellular cyclin D1 levels. These findings suggest that neuronal differentiation of SH-SY5Y cells involves the Wnt signaling pathway and that presenilin 1 plays a crucial role in Wnt signal transduction by regulating the nuclear translocation of ,-catenin. © 2003 Wiley-Liss, Inc. [source] Effect of ropivacaine on endothelium-dependent phenylephrine-induced contraction in guinea pig aortaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2007P. L. Lin Background:, Previous studies have shown that ropivacaine has biphasic vascular effects, causing vasoconstriction at low concentrations and vasorelaxation at high concentrations. This study was designed to examine the role of the endothelium during accidental intravascular absorption of ropivacaine, and to elucidate the mechanisms responsible. Methods:, Isolated guinea pig aortic rings were suspended for isometric tension recording. The effects of ropivacaine on endothelium-intact and endothelium-denuded aortic rings were assessed. Endothelium-intact aortic rings were pre-contracted with phenylephrine before being exposed to ropivacaine and acetylcholine, in order to generate and compare concentration,response curves. In the absence and presence of yohimbine, propranolol, atropine, indometacin, NG -nitro- l -arginine methyl ester (l -NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or methylene blue, the contractile response induced by ropivacaine was assessed on endothelium-intact aortic rings pre-contracted with phenylephrine. Results:, Ropivacaine (3 × 10,4 to 10,2 mol/l) produced vasoconstriction in endothelium-denuded aortic rings, whereas no such response was observed in aortic rings with intact endothelium. In phenylephrine pre-contracted intact aortic rings, ropivacaine induced a greater degree of vasorelaxation than did acetylcholine. Yohimbine, propranolol and atropine all failed to affect the relaxation responses induced by ropivacaine. However, pre-treatment with indometacin (cyclo-oxygenase inhibitor), l -NAME (nitric oxide synthase inhibitor), methylene blue (soluble guanylyl cyclase inhibitor) or ODQ (soluble guanylyl cyclase inhibitor), significantly decreased the ropivacaine-induced relaxation of endothelium-intact aortic rings (3 × 10,4 to 10,2 mol/l). Conclusions:, Ropivacaine elicits an endothelium-dependent vasorelaxation in phenylephrine pre-contracted aortic rings via the nitric oxide,cyclic guanosine 3,,5,-monophosphate pathway and the prostaglandin system. [source] Polyamines Contribute to Ethanol Withdrawal-Induced Neurotoxicity in Rat Hippocampal Slice Cultures Through Interactions With the NMDA ReceptorALCOHOLISM, Issue 7 2003D. Alex Gibson Background: Several reports demonstrate that withdrawal from long-term ethanol exposure is associated with significant central nervous system neurotoxicity, produced at least in part by increased activity of N -methyl-d-aspartate receptors (NMDARs). Recent evidence suggests that elevations in the synthesis and release of the polyamines spermidine and spermine, which are known modulators of NMDARs, contribute to the increased activity of the receptor during ethanol withdrawal. Therefore, the goal of this investigation was to examine what role, if any, spermidine and spermine have in the generation of ethanol withdrawal-induced neurotoxicity. Methods: Neurotoxicity (measured as fluorescence of the cell death indicator propidium iodide, PI), glutamate release (measured by high-performance liquid chromatography analysis), and polyamine concentrations (by high-performance liquid chromatography) were measured in rat hippocampal slice cultures undergoing withdrawal from chronic (10 day) ethanol exposure (100 mM). In addition, the effects of the polyamine synthesis inhibitor di-fluoro-methyl-ornithine (DFMO, 0.1,100 nM) and NMDAR polyamine-site antagonists ifenprodil, arcaine, and agmatine (1 nM-100 ,M) on ethanol withdrawal- and NMDA-induced neurotoxicity were measured. Results: Ethanol withdrawal significantly increased glutamate release (peaking at 18 hr with a 53% increase), increased concentrations of putrescine and spermidine (136% and 139% increases, respectively, at 18 hr), and produced significant cytotoxicity in the CA1 hippocampal region (56% increase in PI staining relative to controls) of the cultures. The cell death produced by ethanol withdrawal was significantly inhibited by ifenprodil (IC50= 14.9 nM), arcaine (IC50= 37.9 nM), agmatine (IC50= 41.5 nM), and DFMO (IC50= 0.6 nM). NMDA (5 ,M) significantly increased PI staining in the CA1 region of the hippocampal cultures (365% relative to controls), but ifenprodil, arcaine, agmatine, and DFMO all failed to significantly affect this type of toxicity. Conclusions: These data implicate a role for polyamines in ethanol withdrawal-induced neurotoxicity and suggest that inhibiting the actions of polyamines on NMDARs may be neuroprotective under these conditions. [source] Dopamine modulates von Willebrand factor secretion in endothelial cells via D2,D4 receptorsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2006S. ZAREI Summary.,Objective: von Willebrand factor (VWF) is acutely released from endothelial cells in response to numerous calcium-raising agents (e.g. thrombin, histamine) and cAMP-raising agents (e.g. epinephrine, adenosine, vasopressin). In contrast, very few inhibitors of endothelial VWF secretion have been described. The neurotransmitter dopamine is a modulator of exocytosis in several endocrine cells, and is possibly involved in the regulation of several endothelial cell functions. We therefore investigated the effect of dopamine on endothelial VWF secretion. Results: Dopamine, D2/D3- and D4-specific agonists inhibited histamine- but not thrombin-induced VWF secretion. Expression of dopamine D2, D3 and D4 receptors was demonstrated by reverse transcription polymerase chain reaction (RT-PCR) in both human aortic (HAEC) and umbilical vein (HUVEC) endothelial cells. D2,D4 agonists did not inhibit histamine-induced rise in [Ca2+]i: they inhibited histamine-induced secretion even in the absence of extracellular calcium. Thus, the dopamine effects are not mediated by [Ca2+]i -dependent signalling. D2/D3- and D4-specific agonists inhibited neither the rise in cAMP nor VWF secretion in response to epinephrine and adenosine, arguing against an effect on cAMP-mediated signalling. D1 and D5 receptors were not detected in HAEC or HUVEC by RT-PCR, and the D1/D5-specific agonist SKF 38 393 failed to modulate VWF secretion, arguing against a role for these receptors in endothelial exocytosis. Conclusions: Dopamine inhibits histamine-induced endothelial exocytosis by activating D2,D4 receptor, via a mechanism distinct from [Ca2+]i -or cAMP-mediated signaling. In contrast, D1 and D5 receptors are not functionally expressed in cultured endothelial cells. Dopamine agonists may be useful as inhibitors of endothelial activation in inflammation and cardiovascular disease. [source] A novel Phe171Cys mutation in integrin ,IIb causes Glanzmann thrombasthenia by abrogating ,IIb,3 complex formationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2004N. Rosenberg Summary.,Background: Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterized by lack of platelet aggregation induced by most agonists. The disease is caused by mutations in either ,IIb[glycoprotein (GP) IIb] or ,3 (GPIIIa) genes that lead to a lack or dysfunction of the integrin ,IIb,3 which serves as a fibrinogen receptor. Patients Mucocutaneous bleeding manifestations and platelet dysfunction consistent with GT were observed in three members of a Cypriot family: a 3-year-old proband, her father and her paternal uncle. Objective: To determine the molecular basis of GT in this family and to characterize possible biochemical and structural defects. Results: Analysis of the patients' platelets by fluorescence-activated cell sorting demonstrated trace amounts of ,3, no ,IIb and no ,IIb,3 on the membrane. Sequence analysis revealed a novel T607G transversion in exon 5 of the ,IIb gene predicting a Phe171Cys alteration that created a PstI recognition site. All three patients were homozygous for the mutation, the mother and paternal grandparents of the proband were heterozygous, whereas 110 healthy subjects lacked this transversion. Chinese hamster ovary cells cotransfected with cDNAs of mutated ,IIb and wild-type ,3 failed to express ,IIb,3 as shown by immunoprecipitation and immunohistochemistry experiments. Structural analysis of the ,IIb,3 model, which was based on the crystal structure of ,v,3, indicated that Phe171 plays an essential role in the interface between the ,-propeller domain of ,IIb and the ,A domain of ,3. Conclusions: A novel Phe171Cys mutation in the ,IIb gene of patients with GT is associated with abrogation of ,IIb,3 complex formation. [source] Tissue- and agonist-specific regulation of human and murine plasminogen activator inhibitor-1 promoters in transgenic miceJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2003M. Eren Summary., Numerous studies have described regulatory factors and sequences that control transcriptional responses in vitro. However, there is a paucity of information on the qualitative and quantitative regulation of heterologous promoters using transgenic strategies. In order to investigate the physiological regulation of human plasminogen activator inhibitor type-1 (hPAI-1) expression in vivo compared to murine PAI-1 (mPAI-1) and to test the physiological relevance of regulatory mechanisms described in vitro, we generated transgenic mice expressing enhanced green fluorescent protein (EGFP) driven by the proximal ,2.9 kb of the hPAI-1 promoter. Transgenic animals were treated with Ang II, TGF-,1 and lipopolysaccharide (LPS) to compare the relative activation of the human and murine PAI-1 promoters. Ang II increased EGFP expression most effectively in brain, kidney and spleen, while mPAI-1 expression was quantitatively enhanced most prominently in heart and spleen. TGF-,1 failed to induce activation of the hPAI-1 promoter but potently stimulated mPAI-1 in kidney and spleen. LPS administration triggered robust expression of mPAI-1 in liver, kidney, pancreas, spleen and lung, while EGFP was induced only modestly in heart and kidney. These results indicate that the transcriptional response of the endogenous mPAI-1 promoter varies widely in terms of location and magnitude of response to specific stimuli. Moreover, the physiological regulation of PAI-1 expression likely involves a complex interaction of transcription factors and DNA sequences that are not adequately replicated by in vitro functional studies focused on the proximal ,2.9 kb promoter. [source] Nutritional status in pregnant adolescents: a systematic review of biochemical markersMATERNAL & CHILD NUTRITION, Issue 2 2007Victoria Hall Moran Abstract Adolescent pregnancy is a major public health challenge for many industrialized countries and is associated with significant medical, nutritional, social and economic risk for mothers and their infants. Despite this, relatively little is known about the nutritional status of this population. The aim of this paper was to conduct a systematic review of the current evidence relating to the biochemical markers of nutritional status of pregnant adolescents living in industrialized countries. Six papers were identified that fulfilled the inclusion criteria, the majority of which were conducted in the United States. The studies were of variable quality and most failed to control for potential confounders which may have strongly influenced the findings. Due to limited research, conclusions cannot be drawn about the zinc and calcium status of pregnant adolescents, and data on folate and vitamin B12 status appeared conflicting. There was some consensus among studies, however, to suggest that indicators of anaemia and iron status were compromised in pregnant adolescents, particularly during the third trimester of pregnancy. Chronological age did not appear to influence nutritional status, although there was some evidence to suggest that increasing gynaecologic age may positively influence plasma ferritin levels. Current research is limited by sampling and measurement bias, and research is urgently required to address these limitations. Further consideration should also be made of the influence of the role of socio-economic support on pregnant adolescents' nutritional status. The achievement of improved nutrition in pregnancy among adolescents requires multidisciplinary collaborations of adolescent healthcare providers, academics, professional organizations, policymakers, industry and service users. Only once this is achieved can adolescent nutrition, and adolescent nutrition in pregnancy, be significantly and sustainably optimized. [source] | |||||||||||||||||||||||||||||||||||||