bluuebunny/crossref_metadata_2025 huggingface dataset:
Aurora A Regulates Prometaphase Progression by Inhibiting the Ability of RASSF1A to Suppress APC-Cdc20 Activity
Authors: Song Su Jung , Song Min Sup , Kim Soon Jung , Kim So Yeon , Kwon Seung Hae , Kim Jhin Gook , Calvisi Diego F. , Kang Dongmin , Lim Dae-Sik
Published: March 2009

The Aurora (Ipl) kinase family plays important roles in the regulation of mitosis and tumorigenesis. The tumor suppressor RASSF1A controls mitotic progression by regulating anaphase-promoting complex (APC)-Cdc20 activity and microtubule stability, but the mechanism by which this action is regulated has not been previously established. Here, we show that Aurora A and B associate with and phosphorylate RASSF1A on serine 203 in vivo at different times and in different subcellular compartments during mitosis. Notably, both depletion of Aurora A by RNA interference and expression of a nonphosphorylatable RASSF1A (S203A) mutant gene led to a marked delay in prometaphase progression. This is likely because of the failure of RASSF1A to dissociate from Cdc20, constitutive inhibition of APC-Cdc20, and accumulation of mitotic cyclins. In contrast, the delay in prometaphase progression caused by Aurora A depletion was largely normalized by phosphomimetic RASSF1A (S203D). Finally, RASSF1A phosphorylation on serine 203 was up-regulated in Aurora A–overexpressing human tumors. These findings indicate that Aurora A plays a critical role in RASSF1A-APC-Cdc20 regulatory mechanisms that control normal prometaphase progression and that are involved in tumorigenesis. [Cancer Res 2009;69(6):2314–23
Associations between Single Nucleotide Polymorphisms in Double-Stranded DNA Repair Pathway Genes and Familial Breast Cancer
Authors: Sehl Mary E. , Langer Lucy R. , Papp Jeanette C. , Kwan Lorna , Seldon Joyce L. , Arellano Geovanni , Reiss Jean , Reed Elaine F. , Dandekar Sugandha , Korin Yael , Sinsheimer Janet S. , Zhang Zuo-Feng , Ganz Patricia A.
Published: March 2009

Purpose: DNA damage recognition and repair play a major role in risk for breast cancer. We investigated 104 single nucleotide polymorphisms (SNP) in 17 genes whose protein products are involved in double-stranded break repair (DSBR).

Experimental Design: We used a case-control design. Both the case individuals affected with breast cancer or with both breast and ovarian cancers and the controls had similar familial risk of breast cancer and were participants in a high-risk cancer registry.

Results: We found that 12 of the polymorphisms are associated with breast or breast and ovarian cancers, most notably rs16888927, rs16888997, and rs16889040, found in introns of RAD21, suggesting that SNPs in other genes in the DSBR pathway in addition to BRCA1 and BRCA2 may affect breast cancer risk.

Conclusions: SNPs within or near several DSBR DNA repair pathway genes are associated with breast cancer in individuals from a high-risk population. In addition, our study reemphasizes the unique perspective that recruitment of cases and controls from family cancer registries has for gene discovery studies.
Enhanced Antitumor Efficacy of a DR5-Specific TRAIL Variant over Recombinant Human TRAIL in a Bioluminescent Ovarian Cancer Xenograft Model
Authors: Duiker Evelien W. , de Vries Elisabeth G.E. , Mahalingam Devalingam , Meersma Gert Jan , Boersma-van Ek Wytske , Hollema Harry , Lub-de Hooge Marjolijn N. , van Dam Go M. , Cool Robbert H. , Quax Wim J. , Samali Afshin , van der Zee Ate G.J. , de Jong Steven
Published: March 2009

Purpose: Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) is clinically evaluated as novel anticancer drug. rhTRAIL-DR5, a rhTRAIL variant that specifically binds to DR5 receptor, has recently been developed. We investigated whether rhTRAIL-DR5 is more efficient than rhTRAIL in combination with cisplatin in DR5-expressing human A2780 ovarian cancer cells.

Design: Effect of cisplatin alone or in combination with rhTRAIL or rhTRAIL-DR5 on DR5 surface expression, apoptosis, and cell survival of A2780 was measured. Biodistribution analysis was done in mice with 125I-rhTRAIL administered intravenously versus intraperitoneally. Antitumor efficacy of rhTRAIL-DR5 versus rhTRAIL was determined in an intraperitoneally growing bioluminescent A2780 xenograft model.

Results: Cisplatin strongly enhanced DR5 surface expression. Both rhTRAIL and rhTRAIL-DR5 in combination with cisplatin induced high levels of caspase-3 activation, apoptosis, and cell kill, with rhTRAIL-DR5 being most potent. Intraperitoneal administration of 125I-rhTRAIL resulted in a 1.7-fold higher area under the curve in serum, increased tumor exposure, and more caspase-3 activation in the tumor than intravenous administration. Intraperitoneal administration of rhTRAIL-DR5 delayed A2780 tumor progression, reflected in a mean light reduction of 68.3% (P = 0.015), whereas rhTRAIL or rhTRAIL-DR5 plus cisplatin resulted in 85% (P = 0.003) and 97% (P = 0.002) reduction compared with A2780 tumor progression in vehicle-treated animals. Combination of rhTRAIL-DR5 with cisplatin was more effective than cisplatin alone (P = 0.027).

Conclusion: rhTRAIL-DR5 was superior over rhTRAIL in vitro and in vivo against DR5-expressing ovarian cancer also in combination with cisplatin. Intraperitoneal administration of rhTRAIL-DR5 warrants further exploration in ovarian cancer.
Enhancement of Lexatumumab-Induced Apoptosis in Human Solid Cancer Cells by Cisplatin in Caspase-Dependent Manner
Authors: Wu Xiu-Xian , Kakehi Yoshiyuki
Published: March 2009

Purpose: This study was designed to evaluate the apoptotic effect of mapatumumab or lexatumumab, human agonistic antibodies that target the tumor necrosis factor–related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2), in combination with chemotherapeutic agents, against human solid cancer cells.

Experimental Design: Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Synergy was assessed by isobolographic analysis.

Results: Treatment of ACHN human renal cell carcinoma cells with cisplatin combined with mapatumumab did not overcome resistance to these agents. However, treatment with cisplatin in combination with lexatumumab had a synergistic cytotoxicity. Synergy was also achieved in six primary renal cell carcinoma cell cultures. Lexatumumab and cisplatin also synergistically enhanced apoptosis. Pretreatment with cisplatin followed by lexatumumab resulted in high cytotoxicity compared with the reverse sequence. Cisplatin significantly increased TRAIL-R2 expression at both the mRNA and the protein levels. Furthermore, the combination of lexatumumab and cisplatin significantly enhanced caspase-8 activity, Bid cleavage, up-regulation of Bax, cytochrome c release, and caspase-9, caspase-6, and caspase-3 activities. Importantly, the activation of caspase-8 was significantly abrogated by the specific inhibitors of caspase-9, caspase-6, and caspase-3. Furthermore, combination-induced cytotoxicity was significantly suppressed by the DR5:Fc chimeric protein and the specific inhibitors of caspase-8, caspase-9, caspase-6, and caspase-3. A similar effect was observed in prostate cancer, bladder cancer, lung cancer, and cervical cancer cells.

Conclusions: Cisplatin sensitizes solid cancer cells to lexatumumab-induced apoptosis by potentiation of the extrinsic and intrinsic apoptotic pathways that lead to amplification of caspase activation, particularly caspase-8, suggesting the combination treatment of solid cancers with cisplatin and lexatumumab might overcome their resistance.
Tie2 in Tumor Endothelial Signaling and Survival: Implications for Antiangiogenic Therapy
Authors: Tsai Jeff H. , Lee William M.F.
Published: March 2009

Signaling through the Tie2 receptor on endothelial cells has been shown to play an important role in normal and pathologic vascular development. We generated K1735 murine melanoma tumor cells that inducibly express soluble Tie2 receptor (Tie2Ex) to study the effects of inhibiting Tie2 signaling on tumor vasculature. Tie2Ex induction rapidly decreased AKT activation but not extracellular signal-regulated kinase (ERK) activation in tumor endothelial cells as detected by immunostaining. This was accompanied by an increase in endothelial cell TUNEL staining but no change in Ki-67 expression. Together with a decrease in the percentage of perfused vessels, this suggested that tumor vessel regression and impaired vascular function rather than angiogenesis inhibition was responsible for the delay in tumor growth following Tie2Ex treatment. However, Tie2Ex failed to inhibit the growth of larger, more established K1735 tumors. These tumors were additionally treated with sorafenib, a multikinase inhibitor that inhibits tumor endothelial cell ERK activation but not AKT activation. Combining Tie2Ex and sorafenib decreased both endothelial cell AKT and ERK activation, decreased endothelial cell survival and proliferation, and significantly inhibited growth of the more established tumors. These studies indicate that activity of specific signaling pathways and prosurvival effects are brought about by Tie2 activation in tumor endothelial cells, and knowledge of the effects of Tie2 inhibition can lead to development of more effective therapeutic regimens for inhibiting tumor neovascularization. (Mol Cancer Res 2009;7(3):300–10)
Dimorphic Expression of dmrt1 and cyp19a1 (Ovarian Aromatase) during Early Gonadal Development in Pejerrey, Odontesthes bonariensis
Authors: Fernandino J.I. , Hattori R.S. , Shinoda T. , Kimura H. , Strobl-Mazzulla P.H. , Strüssmann C.A. , Somoza G.M.
Published: March 2009

The pejerrey (Odontesthes bonariensis) is a teleost fish with strong temperature-dependent sex determination (TSD). Several studies have shown that dmrt1 and gonadal aromatase (cyp19a1) are implicated in the sex differentiation process in teleosts but little is known on the expression balance and endocrine regulation of these two genes during TSD. This study was designed to clarify the expression patterns of both genes during gonadal sex differentiation of pejerrey reared at female-, male- and mixed-sex-producing temperatures (FPT, MPT, and MixPT, respectively). The expression of dmrt1 was found to be significantly higher during gonadal sex differentiation at MPT compared to FPT. Conversely, cyp19a1 expression clearly increased during differentiation at FPT but not at MPT. The expression of both genes at MixPT showed a dimorphic profile with individual values resembling either those at the MPT or FPT. Administration of exogenous 17β-estradiol down- and up-regulated the expression of dmrt1 and cyp19a1, respectively, regardless of temperature, and rescued the female phenotype at the MPT. However, treatment with the aromatase inhibitor Fadrozole caused masculinization without changing the pattern of gene expression. These results are strong evidence of the involvement of both genes in the gonadal differentiation process of pejerrey. The involvement of estradiol is discussed.
Hallmarks of Posttraumatic Stress: Symptom Z-Scores in a Tsunami-Affected Tourist Population
Authors: Heir Trond , Sandvik Leiv , Weisæth Lars
Published: March 2009

Background: To date, little research has been published on the prominence of the various psychiatric symptoms that result from exposure to a natural disaster. In our study of stress-related symptoms among Norwegian tourists who were repatriated after the 2004 southeast Asian tsunami, we evaluated to what extent symptom scores differed between individuals who were exposed to the disaster and those who were not. Methods: Participants (n = 899) completed a questionnaire via post 6 months after the disaster. The participants were categorized according to their level of exposure to the disaster: danger exposed (caught or chased by the waves), nondanger exposed (other disaster-related stressors) and not exposed. Symptoms were assessed by the General Health Questionnaire (GHQ-28), the Post Traumatic Symptom Scale (PTSS-10), and the Impact of Event Scale – Revised (IES-R). We used z-transformation of symptom scores (Z-scores) to evaluate the extent to which symptom scores among disaster-exposed individuals differed from those in the nonexposed reference group. Results: The IES-R revealed the greatest differences between nonexposed and disaster-exposed individuals. Hyperarousal was the most prominent symptom cluster that related to disaster exposure, followed by intrusion and then avoidance. Symptoms of anxiety, social dysfunction, withdrawal, somatization and feelings of guilt were more closely linked to exposure than were symptoms of depression. Conclusions: Our results indicate that symptoms of hyperarousal may be more closely linked to acute exposure to a natural disaster such as a tsunami than other symptoms of psychological distress.
Interferon-α for Treatment of Essential Thrombocythemia during Pregnancy: Case Report and Review of the Literature
Authors: Séror Jérémy , Sentilhes Loïc , Lefebvre-Lacoeuille Céline , Marpeau Loïc
Published: March 2009

Described as a myeloproliferative disorder mainly affecting elderly women, recent reports now confirm the occurrence of essential thrombocythemia at younger ages, which questions treatment during pregnancy. We report a further case of uneventful full term pregnancy with the use of interferon-α for maternal essential thrombocythemia which suggests that interferon-α could be considered as an effective and safe treatment during pregnancy for women with essential thrombocythemia. Further studies are warranted to determine whether interferon-α is the optimal therapeutic option during pregnancy for this patient population.
Fetal Reversed Constrictive Effect of Indomethacin and Postnatal Delayed Closure of the Ductus Arteriosus following Administration of Transplacental Magnesium Sulfate in Rats
Authors: Toyoshima Katsuaki , Momma Kazuo , Nakanishi Toshio
Published: March 2009

Background: Magnesium sulfate (MgSO4) is used therapeutically for eclampsia and tocolysis. Some reports have suggested a relationship between therapeutic MgSO4 and patent ductus arteriosus (DA) in preterm infants. Objectives: To clarify patent DA induction by MgSO4 in preterm infants, we studied the increase in serum Mg concentrations and fetal dilatation and postnatal delayed closure of the ductus, using transplacental MgSO4 in rats. Methods: Fetal and neonatal ductus diameters were measured with a microscope and a micrometer after rapid whole-body freezing. In the postnatal study, 21-day pregnant dams were administered a subcutaneous injection of MgSO4 1–3 h before delivery, and the ductus was studied 0, 15, 30, 60 and 120 min after birth. In the fetal study, MgSO4 (1 g/kg) and indomethacin (10 mg/kg) were simultaneously administered to 21-day dams and the fetal ductus was studied 1, 2 and 4 h later. Serum Mg concentration was measured in the dams and newborns. Results: Neonatal Mg concentrations increased from 3.8 to 4.7 and 5.8 mg/dl at 1 and 3 h after maternal administration of MgSO4. Following MgSO4 administration 3 h before birth, closure of the neonatal DA was delayed. The ductus diameter was 0.88 mm (0.80 mm in control) at 0 min, and 0.26 mm (0.08 mm in the control) at 60 min after birth. In the fetal study, MgSO4 initially reversed and later attenuated the ductus-constricting effect of indomethacin. Conclusions: Hypermagnesemia induced by transplacental MgSO4 attenuates the fetal ductus-constricting effects of indomethacin, and delays postnatal ductal closure in rats.
A Novel Serine Protease Inhibitor Acts as an Immunomodulatory Switch while Maintaining Homeostasis
Authors: Jiang N. , Thangamani S. , Chor C.F. , Wang S.Y. , Winarsih I. , Du R.J. , Sivaraman J. , Ho B. , Ding J.L.
Published: March 2009

Serine protease cascades boost immune responses while maintaining homeostasis. These crucial actions are intricately regulated by cognate serine protease inhibitors. However, the mechanism underlying such a dynamic immunomodulation during acute phase infection remains obscure, particularly where the pathogen’s serine protease adds a new challenge to the host. Here, we found that infection of horseshoe crab, Carcinoscorpius rotundicauda, induced reciprocal profiles of CrSPI (serine protease inhibitor) and CrFurin (serine protease) with respect to their transcription and protein activities. Using recombinant rCrSPI, we explored its inhibitory activity against various microbial proteases and found it most efficacious against a model serine protease, subtilisin A. rCrSPI inhibited subtilisin at Ki 10–9M with a molar ratio of 1 rCrSPI:2 subtilisin. The rCrSPI also inhibited plasma CrFurin, suppressed subtilisin-mediated activation of prophenoloxidase (PPO) and interacted with complement C3. Taken together, CrSPI acts as a key immunomodulatory ‘on-off’ switch in a 2-way regulation of serine protease microbial subtilisin and host serine proteases (CrFurin and CrC3), thereby controlling immune responses involving the complements and the PPO-mediated antimicrobial activities, while maintaining homeostasis.
Estimation of Gamma Raindrop Size Distribution Parameters: Statistical Fluctuations and Estimation Errors
Authors: Mallet Cécile , Barthes Laurent
Published: March 2009

The gamma distribution is often used to characterize raindrop size distributions (DSDs). However, the estimation of measured raindrop distributions suffers from the shortcomings of statistical sampling errors, which become increasingly significant when the collecting surface of the measuring instrument and the integration time are small. Different estimators of the three parameters (N0*, μ, and Dm) that characterize a normalized gamma distribution have been computed from simulated DSD. A database has been established, containing 22 950 simulated DSDs, corresponding to a wide set of various rainfall situations. Moment, least squares, and maximum likelihood estimators have been evaluated. Error measurement considerations are discussed, in particular the difficulty encountered in measuring small drops (diameter <0.5 mm) with a disdrometer. Modified estimation approaches are proposed to compensate for the lack of small drops accounted for by real measurements. For each of the different methods, systematic error analysis is performed, and the estimation error is quantified in terms of its bias and standard deviation. The sensitivity of the various methods to instrumental characteristics is also evaluated. A case study is run to highlight correlation effects in the estimated DSD parameters, resulting from the use of various retrieval techniques.

Finally, a criterion is derived that enables the hypothesis of gamma-distributed DSD to be tested. When applied to real data recorded by an optical disdrometer, this criterion shows that approximately 91% of DSDs are of the gamma type. Real gamma DSDs are then used to compare adapted maximum likelihood estimators with the more commonly used methods.
The Role of Long-Term Trends in Seasonal Predictions: Implication of Global Warming in the NCEP CFS
Authors: Cai Ming , Shin Chul-Su , van den Dool H. M. , Wang Wanqiu , Saha S. , Kumar A.
Published: March 2009

This paper analyzes long-term surface air temperature trends in a 25-yr (1982–2006) dataset of retrospective seasonal climate predictions made by the NCEP Climate Forecast System (CFS), a model that has its atmospheric greenhouse gases fixed at the 1988 concentration level. Although the CFS seasonal forecasts tend to follow the observed interannual variability very closely, there exists a noticeable time-dependent discrepancy between the CFS forecasts and observations, with a warm model bias before 1988 and a cold bias afterward except for a short-lived warm bias during 1992–94. The trend from warm to cold biases is likely caused by not including the observed increase in the anthropogenic greenhouse gases in the CFS, whereas the warm bias in 1992–94 reflects the absence of the anomalous aerosols released by the 1991 Mount Pinatubo eruption. Skill analysis of the CFS seasonal climate predictions with and without the warming trend suggests that the 1997–98 El Niño event contributes significantly to the record-breaking global warmth in 1998 whereas the record-breaking warm decade since 2000 is mainly due to the effects of the increased greenhouse gases. Implications for operational seasonal prediction will be discussed.
An experimental study of the effects of improvisation on the development of children's creative thinking in music
Authors: Koutsoupidou Theano , Hargreaves David J.
Published: March 2009

This article reports a quasi-experimental study of the effects of improvisation on the development of children's creative thinking in music. The study was conducted in a primary school classroom with two matched groups of 6-year-old children over a period of six months. The music lessons for the experimental group were enriched with a variety of improvisatory activities, while those in the control group did not include any improvisation, but instead were didactic and teacher-centred. Children in the experimental group were offered several opportunities to experience improvisation through their voices, their bodies, and musical instruments. Webster's Measure of Creative Thinking in Music — MCTM II (Webster, 1987, 1994) was administered before and after the six-month teaching programmes (i.e., pre-test and post-test) to assess children's creative thinking in terms of four musical parameters: extensiveness, flexibility, originality, and syntax. Analysis revealed that improvisation affects significantly the development of creative thinking; in particular, it promotes musical flexibility, originality, and syntax in children's music-making.
Initial therapy in multiple myeloma: investigating the new treatment paradigm
Authors: Kettle Jacob K , Finkbiner Karen L , Klenke Susan E , Baker Ronald D , Henry Dave W , Williams Casey B
Published: March 2009

The development of three novel chemotherapeutic agents — thalidomide, lenalidomide, and bortezomib — has resulted in a fundamental shift in the management of multiple myeloma. Despite this tremendous advancement, the selection of initial treatment must still be made with a degree of uncertainty as a true standard therapy has yet to be established. Although challenging, the relative abundance of therapeutic options, when taken into consideration with unique patient characteristics, creates the potential for individualization of care.

For patients eligible for autologous stem cell transplantation, various combinations of novel agents with dexamethasone or traditional chemotherapy have supplanted the previous standard regimen consisting of vincristine, doxorubicin, and dexamethasone. In elderly patients or others that are deemed ineligible for the transplant procedure, the addition of a novel agent to melphalan-prednisone has demonstrated significant improvements in response rates. Due to the immaturity of the available data, it is perhaps best to regard the era of novel agents with a degree of rational enthusiasm, as the ultimate impact on patient care remains undetermined. Although further research is clearly implicated, recent advancements have resulted in significant progress toward obtaining optimum outcomes in a historically challenging disease.
Retrospective review of hemoglobin and/or hematocrit levels with occurrence of thrombosis in cancer patients treated with erythropoiesis stimulating agents
Authors: Fullmer Amber C , Miller Rickey
Published: March 2009

Background. No data exists that directly compares hemoglobin and hematocrit levels between cancer patients with and without occurrence of thrombosis during treatment with erythropoiesis stimulating agents (ESAs).

Objective. To determine the association of hemoglobin and hematocrit levels with the occurrence of thrombosis in cancer patients treated with ESAs.

Methods. A retrospective case-control study approved by the Institutional Review Board was conducted on cancer patients billed for epoetin or darbepoetin between 1 July 2002 and 30 June 2007. Cases were defined as patients billed for thrombosis while controls were defined as patients not billed for thrombosis.

Results. Sixteen patients had an occurrence of thrombosis (cases) and were matched to 16 patients that did not have an occurrence of thrombosis (controls) based on age, sex, and cancer type. The mean peak hemoglobin levels for cases and controls were 12.6 ± 1.2 g/dL versus 12.6 ± 1.4 g/dL (p = 0.9). The mean peak hematocrit levels for cases and controls were 37.3 ± 3.8% versus 37.9 ± 4.3% (p = 0.8). For the 16/586 (2.7%) patients with thrombosis, the mean hemoglobin and hematocrit at time of thrombosis were 9.6 ± 1.0 g/dL and 28.9 ± 3.1%. A significant identifiable risk factor for thrombosis between the cases and controls was history of thrombosis 31.3% versus 0% (p = 0.04). Conclusion. There was no statistical difference in peak hemoglobin and hematocrit levels between patients with thrombosis and those without thrombosis. Further study is warranted to determine if these levels are true risk factors for thrombosis.
Encephalopathy secondary to capecitabine chemotherapy: a case report and discussion
Authors: Tipples Karen , Kolluri Rajeev B , Raouf Sherif
Published: March 2009

Introduction. Capecitabine is an oral prodrug of 5-fluorouracil (5-FU) chemotherapy and is licenced for the treatment of breast and gastrointestinal cancers. Multifocal inflammatory leukoencephalopathy has been associated with intravenous 5-FU, but only a few cases of capecitabine-induced encephalopathy have been reported.

Setting. We describe here a case of encephalopathy following administration of Epirubicin/ Cisplatin/Capecitabine chemotherapy, review those cases previously described and suggest recommendations for management.

Results. Symptoms of neurotoxicity from 5-FU and capecitabine usually include confusion, ataxia, nystagmus, dysarthria, sensory loss, and memory loss. Withdrawal of the drug generally leads to improvement of symptoms and steroids are of only questionable benefit.

Conclusion. Patients on fluouropyrimidine drugs with new neurological symptoms should be investigated with brain MRI scan and the drug should be withdrawn until symptoms resolve. Dihydropyrimidine dehydrogenase deficiency should be excluded and ideally an alternative chemotherapy regime sought. We would encourage reporting of such incidences to gain a clearer picture of the incidence and optimal management. J Oncol Pharm Practice (2009) 15: 237—239.
Can the Wolf Motor Function Test be Streamlined?
Authors: Bogard Kimberly , Wolf Steven , Qin Zhang  , Thompson Paul , Morris David , Nichols-Larsen Deborah
Published: March 2009

Background. To assess upper extremity (UE) capabilities following stroke, the Wolf Motor Function Test (WMFT) measures time to complete 15 UE tasks and 2 strength tasks, but takes 30 to 45 minutes for the clinician to complete. Objective. In an effort to streamline the WMFT, this study evaluated the association between the magnitude of improvement on any timed task of the WMFT and the change score on all other tasks among participants in the Extremity Constraint Induced Therapy Evaluation (EXCITE) trial. Methods. This association was evaluated using regression methods according to chronicity and controlling for key covariates (functional level, gender, concordance) for log mean WMFT scores. Results. After controlling for covariates, 6 tasks (hand to table [front], hand to box [front], reach and retrieve, lift can, lift pencil, and fold towel) influenced the overall WMFT score for survivors meeting EXCITE criteria and treated within 3 to 9 months poststroke. Six different tasks (extend elbow weight, hand to box [front], lift can, lift pencil, turn key in lock, and fold towel) influenced the overall WMFT score for those receiving constraint-induced movement therapy (CIMT) 1 year later. The importance of certain tasks relative to others may best represent overall UE function, but this streamlining enables the clinician to prioritize these tasks in the evaluation. Conclusions. The delineation of those tasks depends on the time poststroke from enrollment to CIMT. This study demonstrates that the WMFT can be streamlined from 17 to 6 tasks.
Long-term urethral catheter audit in patients' own homes
Authors: Kneil Carlton , Pellow Heather , Potter Judy
Published: March 2009

Auditing of urinary catheter care generally occurs in clinical environments, either in acute trusts, community hospitals or general practices. This paper reports on an audit that sought to establish the quality of long-term urethral catheter care provided for patients in their own homes. The outcomes identify opportunities to improve the care of these long-term devices, through improved clinical practice by healthcare staff, and opportunites to improve the training and education of patients and their carers.
Early Phase Morphological Lesions and Transcriptional Responses of Bovine Ileum Infected with Mycobacterium avium subsp. paratuberculosis
Authors: Khare S. , Nunes J. S. , Figueiredo J. F. , Lawhon S. D. , Rossetti C. A. , Gull T. , Rice-Ficht A. C. , Adams L. G.
Published: March 2009

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of chronic enteritis in ruminants (Johne's disease) and a possible etiopathologic agent in human Crohn's disease. The host-pathogen interaction in this chronic disease has largely depended on the randomly collected static lesions studied in subclinically or clinically infected animals. We have established and utilized the neonatal calf ligated ileal loop model to study the early temporal host changes during MAP infection. After inoculation of ligated ileal loop with MAP, samples were analyzed for bacterial invasion, histologic and ultrastructural morphologic changes, and gene expression at several times (0.5–12 hours) postinfection. Our results indicate that MAP invades the intestinal mucosa as early as 0.5 hour postinoculation. Distribution and migration of neutrophils, monocytes/macrophages, and goblet cells were confirmed by histopathology, scanning and transmission electron microscopy. Coincident with the morphologic analysis, we measured by real-time polymerase chain reaction gene expression of various cytokines/chemokines that are involved in the recruitment of mononuclear and polymorphonuclear leukocytes to the site of infection. We also detected expression of several other genes, including intestinal-trefoil factor, profilin, lactoferrin, and enteric β-defensin, which may play significant roles in the early MAP infection. Thus, the calf ligated intestinal loop model may be used as a human disease model to understand the role of MAP in the pathogenesis of Crohn's disease.
Degenerative Myelopathy in Two Boxer Dogs
Authors: Miller A. D. , Barber R. , Porter B. F. , Peters R. M. , Kent M. , Platt S. R. , Schatzberg S. J.
Published: March 2009

Degenerative myelopathy (DM) is a common, slowly progressive, debilitating disease reported in several dog breeds, including the German Shepherd Dog and Pembroke Welsh Corgi. Boxer dogs present occasionally for a thoracolumbar myelopathy for which no cause is identified on MRI or cerebrospinal fluid analysis. Despite a lack of a histologic description of DM in the Boxer in the veterinary literature, such dogs are presumed to have DM. Here we report 2 histologically confirmed cases of DM in the Boxer breed in which histologic studies disclosed marked degenerative changes in the spinal cord that were most prominent in the thoracic and cranial lumbar segments. Lesions consisted of myelin vacuolation and degeneration, myelophagocytosis, reactive astrocytosis, and ellipsoid formation most prominent in the lateral and ventral funiculi. We present a detailed histologic description of DM in the Boxer dog and compare it to DM in other purebred dogs.
Chronic Sustained Hypoxia Enhances Both Evoked EPSCs and Norepinephrine Inhibition of Glutamatergic Afferent Inputs in the Nucleus of the Solitary Tract
Authors: Zhang Weirong , Carreño Flávia R. , Cunningham J. Thomas , Mifflin Steve W.
Published: March 2009

The nucleus of the solitary tract (NTS) receives inputs from both arterial chemoreceptors and central noradrenergic neural structures activated during hypoxia. We investigated norepinephrine (NE) modulation of chemoreceptor afferent integration after a chronic exposure to sustained hypoxia (CSH) (7–8 d at 10% FIO2). Whole-cell recordings of NTS second-order neurons identified by DiA (1,1′-dilinoleyl-3,3,3′,3′-tetra-methylindocarbocyanine, 4-chlorobenzenesulphonate) labeling of carotid bodies were obtained in a brain slice. Electrical stimulation of the solitary tract was used to evoke EPSCs. CSH exposure increased evoked EPSC (eEPSC) amplitude via both presynaptic and postsynaptic mechanisms. NE dose dependently decreased the amplitude of eEPSCs. NE increased the paired-pulse ratio of eEPSCs and reduced the frequency of miniature EPSCs, suggesting a presynaptic mechanism. EC50of NE inhibition of eEPSCs was lower in CSH cells (3.0 ± 0.9 μm;n= 5) than in normoxic (NORM) cells (7.6 ± 1.0 μm;n= 7;p< 0.01). NE (10 μm) elicited greater inhibition of eEPSCs in CSH cells (63 ± 2%;n= 16) than NORM cells (45 ± 3%;n= 21;p< 0.01). The α-adrenoreceptor antagonist phentolamine abolished NE inhibition of eEPSCs. CSH enhanced the α2-adrenoreceptor agonist clonidine-mediated inhibition (3 μm; NORM, 23 ± 2%,n= 5 vs CSH, 44 ± 5%,n= 4;p< 0.05) but attenuated α1-adrenoreceptor agonist phenylephrine-mediated inhibition (40 μm; NORM, 36 ± 2%,n= 11 vs CSH, 26 ± 4%,n= 6;p< 0.05). The α2-adrenoreceptor antagonist yohimbine abolished CSH-induced enhancement of NE inhibition of eEPSCs. These results demonstrate that CSH increases evoked excitatory inputs to NTS neurons receiving arterial chemoreceptor inputs. CSH also enhances NE inhibition of glutamate release from inputs to these neurons via presynaptic α2-adrenoreceptors. These changes represent central neural adaptations to CSH.
Uniquely Hominid Features of Adult Human Astrocytes
Authors: Oberheim Nancy Ann , Takano Takahiro , Han Xiaoning , He Wei , Lin Jane H. C. , Wang Fushun , Xu Qiwu , Wyatt Jeffrey D. , Pilcher Webster , Ojemann Jeffrey G. , Ransom Bruce R. , Goldman Steven A. , Nedergaard Maiken
Published: March 2009

Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca2+waves with a speed of 36 μm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca2+in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5–6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.
Peripheral Adaptation Codes for High Odor Concentration in Glomeruli
Authors: Lecoq Jérôme , Tiret Pascale , Charpak Serge
Published: March 2009

Adaptation is a general property of sensory receptor neurons and has been extensively studied in isolated cell preparation of olfactory receptor neurons. In contrast, little is known about the conditions under which peripheral adaptation occurs in the CNS during odorant stimulation. Here, we used two-photon laser-scanning microscopy and targeted extracellular recording in freely breathing anesthetized rats to investigate the correlate of peripheral adaptation at the first synapse of the olfactory pathway in olfactory bulb glomeruli. We find that during sustained stimulation at high concentration, odorants can evoke local field potential (LFP) postsynaptic responses that rapidly adapt with time, some within two inhalations. Simultaneous measurements of LFP and calcium influx at olfactory receptor neuron terminals reveal that postsynaptic adaptation is associated with a decrease in odorant-evoked calcium response, suggesting that it results from a decrease in glutamate release. This glomerular adaptation was concentration-dependent and did not change the glomerular input–output curve. In addition,in situapplication of antagonists of either ionotropic glutamate receptors or metabotropic GABABreceptors did not affect this adaptation, thus discarding the involvement of local presynaptic inhibition. Glomerular adaptation, therefore, reflects the response decline of olfactory receptor neurons to sustained odorant. We postulate that peripheral fast adaptation is a means by which glomerular output codes for high concentration of odor.
Anticoagulation and antiplatelet therapy, and gastrointestinal endoscopy
Authors: Székely Hajnal , Tulassay Zsolt
Published: March 2009

Az utóbbi évtizedben az antikoaguláns és thrombocytaaggregáció-gátló készítmények alkalmazása a különböző szív- és érrendszeri, illetve vérképző szervi betegségekben széles körűvé vált. Ezek a készítmények a thromboemboliás események kockázatának csökkentését szolgálják, ugyanakkor növelik az emésztőrendszeri vérzés lehetőségét. Az endoszkópos beavatkozások során az antikoagulálás felfüggesztése, ezáltal a thromboemboliás szövődmények kialakulásának kockázata minden esetben gondosan mérlegelendő a kezelés folytatásával járó fokozott vérzés kockázatával. Ideiglenes antikoagulálásra szoruló betegeknél (például a mélyvénás thrombosis eseteiben) az elektív endoszkópos beavatkozások későbbi időpontra halasztandók. Kis vérzési kockázatú endoszkópos vizsgálatok előtt (például diagnosztikus vizsgálatok biopsziával) nem szükséges az antikoaguláns kezelés módosítása vagy felfüggesztése. Fokozott vérzési kockázattal járó beavatkozások eseteiben (mint például a polypectomia és a sphincterotomia) egyéni megítélés szükséges; az orális antikoaguláns kezelés felfüggesztése javasolt áthidaló heparinnal vagy a nélkül (a thromboemboliás kockázat függvényében). A thrombocytaaggregáció-gátló készítmények (aszpirin, clopidogrel, ticlopidin) szintén fokozhatják az emésztőrendszeri endoszkópos beavatkozásokkal járó vérzés kockázatát. Felső pánendoszkópia előtt nem szükséges a kezelés felfüggesztése. Egyéb vizsgálatok előtt 4–7 nappal (a szív- és érrendszeri kockázat függvényében) megszakítható a kezelés. Ha az aszpirint elsődleges megelőzésre alkalmaztuk, polypectomia után 14 nappal, sphincterotomiát követően 10 nappal állítható vissza. A másodlagos megelőzés eseteiben a beavatkozást követően egy héttel folytatandó az aszpirin adagolása.
Avaliação nutricional de crianças de seis a sessenta meses
Authors: Sousa Francisca Georgina Macedo de , Araújo Thelma Leite de
Published: March 2009

Este estudo tem como objetivo identificar a situação nutricional de crianças na faixa etária de seis a sessenta meses. Foram utilizadas duas metodologias para definir a condição de nutrição das crianças: critérios de Waterlow e a Curva Peso/Idade do Cartão da Criança. A prevalência de problemas nutricionais foi de 42,9% segundo critérios de Waterlow e 35,6% quando utilizado o critério da Curva Peso/Idade. Propõe-se ações educativas para que a família adote comportamentos e estilos de vida visando reduzir os riscos para o crescimento e desenvolvimento da criança.
A pesquisa em enfermagem no congresso de iniciação científica de uma universidade de São Paulo
Authors: Gomes Maria Magda Ferreira , Sanna Maria Cristina
Published: March 2009

Avaliar a correção metodológica dos trabalhos apresentados pela Faculdade de Enfermagem no 5º Congresso de Iniciação Científica de uma universidade paulista, foi o objetivo deste estudo descritivo feito a partir do resumo publicado nos anais do evento e dos pôsteres expostos. Do total de 42 trabalhos, os objetivos foram adequadamente construídos em 45,2%, enquanto 31% apresentaram-se pouco claros e não mensuráveis. Observou-se mais de uma inadequação metodológica para um mesmo trabalho, num total de 56 ocorrências. Os resultados mostraram-se adequados em 24 trabalhos. 33,3%, dos trabalhos tinham conclusões adequadas, seguidos de 31,5% que não respondiam aos objetivos do estudo. As questões éticas em pesquisa não foram mencionadas em 64,3% dos trabalhos. A comparação com trabalhos de mesma temática efetuados por outros pesquisadores brasileiros, indicou que a atividade de pesquisa desta faculdade de enfermagem está requerendo investimentos na capacitação dos orientadores para atender à necessidade de fortalecimento da atividade.
Consulta de enfermagem ao cliente transplantado cardíaco: impacto das ações educativas em saúde
Authors: Santos Zélia Maria de Sousa Araújo , Oliveira Vera Lúcia Mendes de
Published: March 2009

O estudo teve como objetivo avaliar o impacto das ações educativas em saúde, na consulta de Enfermagem com 18 clientes transplantados cardíacos, embasado na Teoria de Orem. Foi realizado em uma Unidade de Transplante e Insuficiência Cardíaca de uma Instituição Pública de Saúde de Fortaleza - Ce. Os dados foram coletados através da consulta de Enfermagem. Identificou-se 14 diagnósticos de enfermagem na primeira consulta e 7 na última. Constatou-se que, os clientes desenvolveram habilidades para o autocuidado, com a implementação das ações educativas em saúde, tornando-os agentes de autocuidado, com o alcance de um bom nível de saúde e bem-estar. Por outro lado, despertou no enfermeiro, um direcionamento sistemático e eficaz no acompanhamento ambulatorial a esta clientela.
A enfermeira no processo de descentralização do sistema de saúde
Authors: Borges Maria Aparecida Santa Fé , Nascimento Maria Ângela Alves do
Published: March 2009

Estudo sobre o processo de descentralização do sistema de saúde nas décadas de 80 e 90 no município de Itabuna-BA; com o objetivo de descrever o processo de descentralização da saúde no município, identificando a inserção/participação da enfermeira nesse processo. Estudo descritivo, qualitativo de caráter exploratório, que utilizou para coleta de dados a entrevista semi-estruturada, e a análise documental. Os resultados apontam que a inserção da enfermeira no processo da descentralização seguiu-se de acordo com as mudanças transcorridas a cada gestão municipal, onde ela atuou mais efetivamente conforme foi o cenário estabelecido e sofreu influência das diversas conjunturas conformadas pelas políticas implantadas ou implementadas em cada contexto da gestão do Sistema de saúde municipal.
Formação de Enfermeiros na perspectiva da Reforma Psiquiátrica
Authors: Silva Ana Tereza Medeiros da , Souza Jordana Silva de , Silva César Cavalcanti da , Nóbrega Maria Miriam Lima da , Oliveira Filha Maria de , Barros Sônia , Braga João Euclides
Published: March 2009

Este estudo é resultado de uma pesquisa com alunos concluintes do Curso de Enfermagem, sobre as concepções do processo saúde-doença mental na perspectiva da Reforma Psiquiátrica proposta no país. Foi orientado pelo referencial teórico-metodológico do Materialismo Histórico e Dialético e tem o Trabalho, como categoria de análise. O material empírico foi analisado pela técnica de Análise do Discurso. Os temas depreendidos dos discursos convergiram para a formação de uma categoria empírica que se refere à reprodução do saber da psiquiatria tradicional no ensino de enfermagem, indicando uma formação profissional ancorada nessa posição social conservadora.
O gênero (in)visível da terceira idade no saber da enfermagem
Authors: Figueiredo Maria do Livramento Fortes , Tyrrell Maria Antonieta Rubio
Published: March 2009

Trata-se de um estudo bibliográfico, no qual realizou-se um levantamento da produção científica de enfermagem referente à Mulher na Terceira Idade no Catálogo de Dissertações e Teses do CD-room do Centro de Estudos e Pesquisas em Enfermagem(CEPEn) da Associação Brasileira de Enfermagem - ABEn no período de 1979 a 1999. Objetivou conhecer os afastamentos e/ou aproximações no saber de enfermagem com o objeto de estudo da tese de doutorado: os saberes e práticas de saúde das mulheres idosas, na perspectiva de gênero. Concluiu-se que a mulher na terceira idade foi investigada em poucos estudos, além do mais, os objetos destas investigações se afastaram fortemente das questões de gênero, demonstrando-se o aspecto assexuado da velhice, e negação dos papéis sociais da mulher.
Profissional crítico-criativa em enfermagem: a construção do espaço interseçor na relação pedagógica
Authors: Reibnitz Kenya Schmidt
Published: March 2009

Este estudo tem como objetivo compreender como se manifesta o espaço interseçor na relação pedagógica num Curso de Graduação em Enfermagem. Está fundamentado no referencial teórico de Merhy, o qual estabelece o espaço interseçor no processo de trabalho em saúde como o momento que pode propiciar a implantação de mudanças. A metodologia utilizada está baseada na abordagem qualitativa do tipo estudo de caso instrumental utilizando a técnica de observação nos espaços formais do ensino. Identificamos um descompasso entre os programas instituídos e a curiosidade, reafirmando que o processo educativo precisa ser um ato cognoscente entre sujeitos, numa relação dialógica mediada pela palavra, pelas emoções e pelos objetos cognoscíveis e concluímos que a relação pedagógica instituínte representa um compromisso com a transformação das práticas em saúde.
Resíduos potencialmente infectantes em serviços de hemoterapia e as interfaces com as doenças infecciosas
Authors: Prado Marinésia Aparecida do , Melo Dulcelene de Sousa , Machado Katiusse Macedo , Santos Silvana de Lima Vieira dos , Gir Elucir , Canini Silvia Rita Marin da Silva , Pelá Nilza Tereza Rotter
Published: March 2009

Objetivou-se identificar o processamento de resíduos potencialmente infectantes e de perfurocortantes em unidades de hemoterapia e sua possível relação com a saúde dos trabalhadores. Nenhum serviço apresentou plano estruturado para o gerenciamento de resíduos de serviços de saúde e para o programa de segurança ocupacional. Verificou-se um índice de acidentes ocupacionais de 32, 82 % e que 9,16% dos trabalhadores estavam com esquema incompleto de vacinação contra hepatite B. Os treinamentos em serviços para manejo de resíduos e saúde ocupacional não são padronizados. O índice de soroconversão para VHB e VHC após exposição ocupacional foi de 11,63%. Concluímos que o processamento de resíduos potencialmente infectantes e perfurocortantes nas unidades de hemoterapias pesquisadas tem exposto os trabalhadores à aquisição de doenças infecciosas.
Cuidado humanizado no ensino de enfermagem
Authors: Motta Maria da Graça
Published: March 2009

Este relato de experiência docente desenvolve conteúdos relacionados ao cuidado humanizado à criança/adolescente e sua família, com os acadêmicos do Curso de Graduação em Enfermagem. Utiliza-se como metodologia as oficinas de Criatividade e Sensibilidade propostas por Cabra(1)l (1999) que se revelaram adequadas para abordar temas complexos como prevenção da violência contra criança/adolescente e o cuidado a famílias que vivenciam a doença do filho. Durante as oficinas, busca-se criar um espaço para a reflexão sobre o cuidado humanizado a partir da vivência dos acadêmicos. Verifica-se a importância de introduzir metodologias alternativas no processo de ensino aprendizagem do acadêmico buscando a construção do conhecimento e privilegiando a sua experiência.