abstract: @entity0 apical @entity6 -dependent @entity13 transporter ( @entity18 ) is a potential prodrug target under study. Development of prodrugs that target @entity18 may yield compounds with low solubility and/or susceptibility to hydrolysis. A transport uptake method is needed that increases compound solubility and avoids @entity12 for cell lysis during postexperimental cell sample preparation. The overall goal was to develop an assay method to screen for @entity18 uptake of novel compounds. The first objective was to determine the maximum cosolvent concentrations that are compatible with an @entity18 active transport assay. The second objective was to develop a @entity12 -free cell lysis method to process cell samples from these uptake studies. The following cosolvents were studied: @entity16 ( @entity17 ), @entity11 ( @entity15 ), @entity9 ( @entity9 ), @entity5 , @entity4 , @entity3 , @entity8 , and @entity10 . Initial studies included @entity14 flux studies across @entity18 -Madin-Darby @entity2 kidney monolayers using up to 10% cosolvent, as well as @entity1 studies. The effect of selected cosolvent concentrations on the @entity18 Michaelis-Menten kinetic parameters was evaluated. Additionally, two @entity7 -based cell lysis methods that do not use @entity12 were evaluated in terms of percent sample recovery and @entity18 kinetic parameters. Results showed that the maximum permissible cosolvent concentrations for @entity18 uptake studies, without compromising assay results or causing @entity1 , are 1% @entity17 , 1% @entity15 , 2.5% @entity9 , 2.5% @entity4 , and 2.5% @entity5 . Additionally, both @entity12 -free, @entity7 -based cell lysis methods provided similar recovery and @entity18 results, compared to @entity12 method. Hence, an assay method was developed to screen for active transport, allowing for cosolvents that can solubilize compounds and avoid @entity12 sample treatment, which can otherwise degrade compound.

title: Method to screen substrates of apical @entity6 -dependent XXXX transporter.

answer: @entity13


abstract: BACKGROUND: @entity7 ( @entity7 ) is a severe @entity2 defined principally by its tendency to selectively affect optic nerves and the spinal cord causing recurrent attacks of @entity8 and @entity6 . Contemporary diagnostic criteria require absence of clinical disease outside the optic nerve or spinal cord. We have, however, frequently encountered @entity0 with a well-established diagnosis of @entity7 in whom either asymptomatic or symptomatic @entity3 develop suggesting that the diagnostic criteria for @entity7 should be revised. OBJECTIVE: To describe the magnetic resonance image (MRI) brain findings in @entity7 . DESIGN: Observational, retrospective case series. @entity0 We ascertained @entity0 through a clinical biospecimens database of individuals with definite or suspected @entity7 . We included @entity0 who (1) satisfied the 1999 criteria of Wingerchuk et al for @entity7 except for the absolute criterion of lacking symptoms beyond the optic nerve and spinal cord and the supportive criterion of having a normal brain MRI at onset; (2) had MRI evidence of a spinal cord lesion extending 3 vertebral segments or more (the most specific nonserological feature to differentiate @entity7 from MS); and (3) were evaluated neurologically and by brain MRI at the Mayo Clinic. MAIN OUTCOME MEASURES: Magnetic resonance images were classified as normal or as abnormal with either nonspecific, @entity1 -like or @entity5 . We evaluated whether @entity3 were symptomatic and analyzed the neuropathologic features of a single brain biopsy specimen. RESULTS: Sixty @entity0 (53 @entity0 [88%]) fulfilled these inclusion criteria. The mean +/- SD age at onset was 37.2 +/- 18.4 years and the mean +/- SD duration of follow-up was 6.0 +/- 5.6 years. @entity7 -IgG was detected in 41 @entity0 (68%). @entity3 were detected in 36 @entity0 (60%). Most were nonspecific, but 6 @entity0 (10%) had @entity9 , usually asymptomatic. Another 5 @entity0 (8%), mostly @entity0 , had diencephalic, brainstem or @entity3 , atypical for @entity1 . When present, symptoms of brain involvement were subtle, except in 1 @entity0 who was @entity4 and had large @entity3 . CONCLUSIONS: Asymptomatic @entity3 are common in @entity7 , and symptomatic @entity3 do not exclude the diagnosis of @entity7 . These observations justify revision of diagnostic criteria for @entity7 to allow for brain involvement.

title: @entity3 in XXXX .

answer: @entity7


abstract: BACKGROUND: @entity7 ( @entity7 ) is a severe @entity2 defined principally by its tendency to selectively affect optic nerves and the spinal cord causing recurrent attacks of @entity8 and @entity6 . Contemporary diagnostic criteria require absence of clinical disease outside the optic nerve or spinal cord. We have, however, frequently encountered @entity0 with a well-established diagnosis of @entity7 in whom either asymptomatic or symptomatic @entity3 develop suggesting that the diagnostic criteria for @entity7 should be revised. OBJECTIVE: To describe the magnetic resonance image (MRI) brain findings in @entity7 . DESIGN: Observational, retrospective case series. @entity0 We ascertained @entity0 through a clinical biospecimens database of individuals with definite or suspected @entity7 . We included @entity0 who (1) satisfied the 1999 criteria of Wingerchuk et al for @entity7 except for the absolute criterion of lacking symptoms beyond the optic nerve and spinal cord and the supportive criterion of having a normal brain MRI at onset; (2) had MRI evidence of a spinal cord lesion extending 3 vertebral segments or more (the most specific nonserological feature to differentiate @entity7 from MS); and (3) were evaluated neurologically and by brain MRI at the Mayo Clinic. MAIN OUTCOME MEASURES: Magnetic resonance images were classified as normal or as abnormal with either nonspecific, @entity1 -like or @entity5 . We evaluated whether @entity3 were symptomatic and analyzed the neuropathologic features of a single brain biopsy specimen. RESULTS: Sixty @entity0 (53 @entity0 [88%]) fulfilled these inclusion criteria. The mean +/- SD age at onset was 37.2 +/- 18.4 years and the mean +/- SD duration of follow-up was 6.0 +/- 5.6 years. @entity7 -IgG was detected in 41 @entity0 (68%). @entity3 were detected in 36 @entity0 (60%). Most were nonspecific, but 6 @entity0 (10%) had @entity9 , usually asymptomatic. Another 5 @entity0 (8%), mostly @entity0 , had diencephalic, brainstem or @entity3 , atypical for @entity1 . When present, symptoms of brain involvement were subtle, except in 1 @entity0 who was @entity4 and had large @entity3 . CONCLUSIONS: Asymptomatic @entity3 are common in @entity7 , and symptomatic @entity3 do not exclude the diagnosis of @entity7 . These observations justify revision of diagnostic criteria for @entity7 to allow for brain involvement.

title: XXXX in @entity7 .

answer: @entity3


abstract: OBJECTIVE: To summarize the experience in @entity6 in the treatment of @entity7 . METHOD: The clinical data of 35 @entity0 with @entity7 diagnosed by CT and MRI, 26 males and 9 females; aged 13 (1 - 54), with the main clinical presentations of @entity3 and ex-ophthalmo and with the courses from 1 to 36 months, who underwent operation via the @entity6 36 times, were analyzed. The diagnosis was confirmed by pathology after operation in 35 cases. Follow-up was conducted for 3 months to 8 years. RESULTS: Total resection was achieved in 29 cases, and subtotal resection in 6 cases. The surgical complications included @entity8 (2 cases) and @entity4 (1 cases), and no @entity5 was found. The follow-up rate was 77.1% (27/35). Three cases suffered from recurrence, spinal @entity1 was found in 1 case, and 1 case died. CONCLUSION: resection of @entity7 via @entity6 is effective. However, since @entity2 may remain in the optic nerve canal, post-operative radiation therapy is recommended.

title: [Cranial-orbital approach in the treatment of XXXX ].

answer: @entity7


abstract: BACKGROUND: A paradoxical increase in the uncorrected QT interval during infusion of low-dose @entity2 appears pathognomonic for @entity6 ( @entity4 ). We sought to determine the diagnostic accuracy of this response among @entity0 referred for clinical evaluation of @entity1 (LQTS). METHODS AND RESULTS: From 1999 to 2002, 147 genotyped @entity0 (125 untreated and 22 undergoing beta-blocker therapy) had an @entity2 QT stress test that involved a 25-minute infusion protocol (0.025 to 0.3 microg.kg(-1).min(-1)). A 12-lead ECG was monitored continuously, and repolarization parameters were measured. The sensitivity, specificity, and positive and negative predictive values for the @entity1 (defined as a > or =30-ms increase in QT during infusion of < or =0.1 microg.kg(-1).min(-1) @entity2 ) was determined. The 125 untreated @entity0 (44 genotype negative, 40 @entity4 , 30 @entity5 , and 11 @entity3 ) constituted the primary analysis. The median baseline corrected QT intervals (QTc) were 444 ms (gene negative), 456 ms ( @entity4 ), 486 ms ( @entity5 ), and 473 ms ( @entity3 ). The median change in QT interval during low-dose @entity2 infusion was -23 ms in the gene-negative group, 78 ms in @entity4 , -4 ms in @entity5 , and -58 ms in @entity3 . The @entity1 was observed in 37 (92%) of 40 @entity0 with @entity4 compared with 18% (gene-negative), 13% ( @entity5 ), and 0% ( @entity3 ; P<0.0001) of the remaining @entity0 . Overall, the @entity1 had a sensitivity of 92.5%, specificity of 86%, positive predictive value of 76%, and negative predictive value of 96% for @entity4 status. Secondary analysis of the subset undergoing beta-blocker therapy indicated inferior diagnostic utility in this setting. CONCLUSIONS: The @entity2 QT stress test can unmask concealed type 1 LQTS with a high level of accuracy.

title: XXXX QT stress testing in the evaluation of @entity1 : diagnostic accuracy of the @entity1 .

answer: @entity2


abstract: BACKGROUND: A paradoxical increase in the uncorrected QT interval during infusion of low-dose @entity2 appears pathognomonic for @entity6 ( @entity4 ). We sought to determine the diagnostic accuracy of this response among @entity0 referred for clinical evaluation of @entity1 (LQTS). METHODS AND RESULTS: From 1999 to 2002, 147 genotyped @entity0 (125 untreated and 22 undergoing beta-blocker therapy) had an @entity2 QT stress test that involved a 25-minute infusion protocol (0.025 to 0.3 microg.kg(-1).min(-1)). A 12-lead ECG was monitored continuously, and repolarization parameters were measured. The sensitivity, specificity, and positive and negative predictive values for the @entity1 (defined as a > or =30-ms increase in QT during infusion of < or =0.1 microg.kg(-1).min(-1) @entity2 ) was determined. The 125 untreated @entity0 (44 genotype negative, 40 @entity4 , 30 @entity5 , and 11 @entity3 ) constituted the primary analysis. The median baseline corrected QT intervals (QTc) were 444 ms (gene negative), 456 ms ( @entity4 ), 486 ms ( @entity5 ), and 473 ms ( @entity3 ). The median change in QT interval during low-dose @entity2 infusion was -23 ms in the gene-negative group, 78 ms in @entity4 , -4 ms in @entity5 , and -58 ms in @entity3 . The @entity1 was observed in 37 (92%) of 40 @entity0 with @entity4 compared with 18% (gene-negative), 13% ( @entity5 ), and 0% ( @entity3 ; P<0.0001) of the remaining @entity0 . Overall, the @entity1 had a sensitivity of 92.5%, specificity of 86%, positive predictive value of 76%, and negative predictive value of 96% for @entity4 status. Secondary analysis of the subset undergoing beta-blocker therapy indicated inferior diagnostic utility in this setting. CONCLUSIONS: The @entity2 QT stress test can unmask concealed type 1 LQTS with a high level of accuracy.

title: @entity2 QT stress testing in the evaluation of XXXX : diagnostic accuracy of the @entity1 .

answer: @entity1


abstract: BACKGROUND: A paradoxical increase in the uncorrected QT interval during infusion of low-dose @entity2 appears pathognomonic for @entity6 ( @entity4 ). We sought to determine the diagnostic accuracy of this response among @entity0 referred for clinical evaluation of @entity1 (LQTS). METHODS AND RESULTS: From 1999 to 2002, 147 genotyped @entity0 (125 untreated and 22 undergoing beta-blocker therapy) had an @entity2 QT stress test that involved a 25-minute infusion protocol (0.025 to 0.3 microg.kg(-1).min(-1)). A 12-lead ECG was monitored continuously, and repolarization parameters were measured. The sensitivity, specificity, and positive and negative predictive values for the @entity1 (defined as a > or =30-ms increase in QT during infusion of < or =0.1 microg.kg(-1).min(-1) @entity2 ) was determined. The 125 untreated @entity0 (44 genotype negative, 40 @entity4 , 30 @entity5 , and 11 @entity3 ) constituted the primary analysis. The median baseline corrected QT intervals (QTc) were 444 ms (gene negative), 456 ms ( @entity4 ), 486 ms ( @entity5 ), and 473 ms ( @entity3 ). The median change in QT interval during low-dose @entity2 infusion was -23 ms in the gene-negative group, 78 ms in @entity4 , -4 ms in @entity5 , and -58 ms in @entity3 . The @entity1 was observed in 37 (92%) of 40 @entity0 with @entity4 compared with 18% (gene-negative), 13% ( @entity5 ), and 0% ( @entity3 ; P<0.0001) of the remaining @entity0 . Overall, the @entity1 had a sensitivity of 92.5%, specificity of 86%, positive predictive value of 76%, and negative predictive value of 96% for @entity4 status. Secondary analysis of the subset undergoing beta-blocker therapy indicated inferior diagnostic utility in this setting. CONCLUSIONS: The @entity2 QT stress test can unmask concealed type 1 LQTS with a high level of accuracy.

title: @entity2 QT stress testing in the evaluation of @entity1 : diagnostic accuracy of the XXXX .

answer: @entity1


abstract: INTRODUCTION: We conducted a quality assurance project of The Mobile Emergency Care Unit (MECU) in the Capital Region of Denmark when dispatched to febrile @entity1 . The study focuses on prehospital treatment, comparison between prehospital and in-hospital diagnoses and parents' perceptions of their @entity0 's febrile @entity1 and their satisfaction with the MECU. MATERIAL AND METHODS: The period of investigation was from March 1st 2004 to March 31st 2005. @entity0 with a diagnosis of febrile @entity1 or relevant differential diagnoses were eligible for inclusion. @entity0 were excluded if they had already been included, if their parents had no Danish address or if the questionnaire was not returned after a reminder was sent. RESULTS: In the period of investigation, 333 @entity0 were eligible for inclusion, 290 questionnaires were sent, and 235 were returned, giving a response rate of 81%. The median age was 1 year (range: 0-7 years). In general, parents were satisfied with the MECU. Reasons of dissatisfaction are described. Most @entity0 (76%) were admitted without physician escort. A total of 37 @entity0 (16%) received @entity2 therapy, of whom 15 (6%) were given intravenous @entity2 . In 90% of cases, the prehospital and in-hospital diagnosis were identical. CONCLUSION: In general, parents appreciate the service provided by the MECU. Reasons of dissatisfaction are described. On several occasions, the prehospital physician administered intravenous anticonvulsants, but we discuss if the MECU should still be dispatched primarily to febrile @entity1 .

title: [Prehospital management of febrile XXXX by the Mobile Emergency Care Unit in the Capital Region of Denmark].

answer: @entity1


abstract: Three cases of @entity6 ( @entity6 ) in the @entity5 were encountered during a period of 12 years and bladder preserving treatments were performed. Case 1: A 78-year-old @entity0 was admitted with a chief complaint of @entity4 . @entity1 in the diverticulum of the right bladder wall were revealed ( @entity6 , G3, T3N0M0). Intraarterial infusion chemotherapy was performed and complete remission was achieved. When a recurrent @entity2 appeared 22 months later, transurethral resection was performed and there was no evidence of recurrence for 50 months. Case 2: A 60-year-old @entity0 was admitted with a chief complaint of gross @entity4 . Cystoscopic examination revealed @entity1 in a @entity5 near the ureteral left orifice. Transurethral resection revealed @entity3 in situ. Partial cystectomy, including the @entity5 , and vesicoureteral neostomy was performed. The histological stage of the @entity1 was pTis and the wall of diverticulum possessed a thin muscle layer histopathologically. Twenty two months later, recurrence in the left bladder wall developed and transurethral resection and bladder instillation therapy were performed. For 21 months he had no evidence of recurrence. Case 3: A 59-year-old @entity0 was admitted with a chief complaint of @entity4 . A solid @entity1 in the diverticulum of the bladder left wall was revealed. After 4 courses of intraarterial infusion chemotherapy, 41% remission was achieved and partial cystectomy was performed. Histopathological diagnosis was @entity6 G3, pT3b, @entity7 , v (-), ly (-), and no muscle layer was found in the diverticulum. There was no evidence of recurrence 16 months after operation. By using the combination therapy, bladder preserving treatment is possible in the cases of @entity2 arising in the diverticulum.

title: [Three cases of XXXX in @entity5 treated by a bladder-preserving approach].

answer: @entity6


abstract: Three cases of @entity6 ( @entity6 ) in the @entity5 were encountered during a period of 12 years and bladder preserving treatments were performed. Case 1: A 78-year-old @entity0 was admitted with a chief complaint of @entity4 . @entity1 in the diverticulum of the right bladder wall were revealed ( @entity6 , G3, T3N0M0). Intraarterial infusion chemotherapy was performed and complete remission was achieved. When a recurrent @entity2 appeared 22 months later, transurethral resection was performed and there was no evidence of recurrence for 50 months. Case 2: A 60-year-old @entity0 was admitted with a chief complaint of gross @entity4 . Cystoscopic examination revealed @entity1 in a @entity5 near the ureteral left orifice. Transurethral resection revealed @entity3 in situ. Partial cystectomy, including the @entity5 , and vesicoureteral neostomy was performed. The histological stage of the @entity1 was pTis and the wall of diverticulum possessed a thin muscle layer histopathologically. Twenty two months later, recurrence in the left bladder wall developed and transurethral resection and bladder instillation therapy were performed. For 21 months he had no evidence of recurrence. Case 3: A 59-year-old @entity0 was admitted with a chief complaint of @entity4 . A solid @entity1 in the diverticulum of the bladder left wall was revealed. After 4 courses of intraarterial infusion chemotherapy, 41% remission was achieved and partial cystectomy was performed. Histopathological diagnosis was @entity6 G3, pT3b, @entity7 , v (-), ly (-), and no muscle layer was found in the diverticulum. There was no evidence of recurrence 16 months after operation. By using the combination therapy, bladder preserving treatment is possible in the cases of @entity2 arising in the diverticulum.

title: [Three cases of @entity6 in XXXX treated by a bladder-preserving approach].

answer: @entity5


abstract: While realizing the difficulties with the various methods used to study hormonal control of protein metabolism, there appear to be clear effects of both rapid-acting and slower-acting hormones. Moreover, some of these hormones affect protein metabolism in a dose dependent manner. @entity5 and @entity2 appear to have differing effects at lower doses, with @entity5 primarily inhibiting protein degradation and @entity2 stimulating protein synthesis. At higher doses, infusions of @entity5 and @entity2 both seem to inhibit protein degradation and stimulate protein synthesis. @entity3 primarily inhibits protein degradation whereas growth hormone primarily increases protein synthesis. Infusion of @entity4 themselves can also increase protein synthesis. Thyroid hormone excess increases protein synthesis and protein degradation, with the latter effect predominating. Sex @entity1 appear to increase protein synthesis. To date, most interventions studying the metabolic effects of these hormones on protein metabolism have involved varying the concentration of one hormone at a time. In the complex milieu of many pathologic states (e.g. sepsis, @entity0 or even the transition from fasting to feeding) multiple hormones change simultaneously. How interactions among these factors determine the overall response of body and muscle protein remains to be defined.

title: The role of XXXX and other hormones in the regulation of amino acid and protein metabolism in humans.

answer: @entity5


abstract: PURPOSE OF REVIEW: This article reviews recent advances in multimodality monitoring of @entity0 following severe @entity3 during the period of 2004-2005. RECENT FINDINGS: Whilst intracranial pressure measurement remains the cornerstone of neuromonitoring, analysis of the intracranial pressure waveform provides additional information, which may help guide treatment and predict outcome. Non-invasive detection of intracranial @entity2 and assessment of cerebral perfusion pressure and autoregulation is the focus of ongoing research. Although jugular venous saturation monitoring remains a useful method for detecting global hypoperfusion its sensitivity to regional ischaemia is low. Brain tissue @entity1 monitoring overcomes this deficiency and sheds new light on the pathophysiology of @entity5 following @entity4 . Further studies are required to define ischaemic thresholds and their association with outcome. Extracellular brain pH has been recently linked to outcome and further studies are required to establish the role of pH regulation. Monitoring of brain metabolism using a cerebral microdialysis continues to develop its niche in clinical neuromonitoring, although it currently remains a research tool. SUMMARY: Multimodality neuromonitoring plays an important role in managing @entity0 with severe @entity3 . It helps guide treatment, provides prognostic information and explores the pathophysiology of evolving @entity4 .

title: Monitoring of head injured XXXX .

answer: @entity0


abstract: PURPOSE: The high molecular weight @entity3 -associated antigen (HMW-MAA) is an attractive target for immunotherapy of @entity3 . We have recently generated a vaccine based on the HMW-MAA mimotope 225D9.2+ that was able to induce anti-HMW-MAA antibodies with antitumor activity in vitro. Here, we investigated the antitumor activity of these antibodies in a @entity0 @entity3 xenotransplant @entity4 ( @entity4 ) @entity2 model. EXPERIMENTAL DESIGN: @entity1 were established by injecting the @entity0 @entity3 518A2 cells into C.B.17 @entity4 / @entity4 @entity2 . In @entity1 prevention experiments, 200 microg purified total IgG antibodies were injected intravenously the same day or on day 5 in therapeutic experiments. Antibody administration was repeated every fourth day and @entity1 volumes were measured. Antibody specificity and @entity1 infiltration by macrophages were investigated by immunohistochemistry. RESULTS: Within 35 days after cell inoculation, antibody treatment reduced @entity1 growth up to 40% in the therapeutic and up to 62% in the @entity1 prevention experiments compared with the control @entity2 . In @entity1 of all groups, a similar distribution of the HMW-MAA and no differences in infiltration of macrophages were detected by immunohistochemistry. CONCLUSIONS: Here, we showed that antibodies induced by the 225D9.2+ mimotope effectively inhibited @entity3 growth. Additional mechanisms besides antibody-dependent cell cytotoxicity like disruption of interactions of @entity3 cells mediated by extracellular matrix components seem to be involved in @entity1 growth inhibition. Based on our findings, we suggest that active immunization with this mimotope might be a promising strategy for treatment of @entity3 .

title: Reduction of XXXX @entity3 growth in @entity4 @entity2 by passive transfer of antibodies induced by a high molecular weight @entity3 -associated antigen mimotope vaccine.

answer: @entity0


abstract: PURPOSE: The high molecular weight @entity3 -associated antigen (HMW-MAA) is an attractive target for immunotherapy of @entity3 . We have recently generated a vaccine based on the HMW-MAA mimotope 225D9.2+ that was able to induce anti-HMW-MAA antibodies with antitumor activity in vitro. Here, we investigated the antitumor activity of these antibodies in a @entity0 @entity3 xenotransplant @entity4 ( @entity4 ) @entity2 model. EXPERIMENTAL DESIGN: @entity1 were established by injecting the @entity0 @entity3 518A2 cells into C.B.17 @entity4 / @entity4 @entity2 . In @entity1 prevention experiments, 200 microg purified total IgG antibodies were injected intravenously the same day or on day 5 in therapeutic experiments. Antibody administration was repeated every fourth day and @entity1 volumes were measured. Antibody specificity and @entity1 infiltration by macrophages were investigated by immunohistochemistry. RESULTS: Within 35 days after cell inoculation, antibody treatment reduced @entity1 growth up to 40% in the therapeutic and up to 62% in the @entity1 prevention experiments compared with the control @entity2 . In @entity1 of all groups, a similar distribution of the HMW-MAA and no differences in infiltration of macrophages were detected by immunohistochemistry. CONCLUSIONS: Here, we showed that antibodies induced by the 225D9.2+ mimotope effectively inhibited @entity3 growth. Additional mechanisms besides antibody-dependent cell cytotoxicity like disruption of interactions of @entity3 cells mediated by extracellular matrix components seem to be involved in @entity1 growth inhibition. Based on our findings, we suggest that active immunization with this mimotope might be a promising strategy for treatment of @entity3 .

title: Reduction of @entity0 XXXX growth in @entity4 @entity2 by passive transfer of antibodies induced by a high molecular weight @entity3 -associated antigen mimotope vaccine.

answer: @entity3


abstract: PURPOSE: The high molecular weight @entity3 -associated antigen (HMW-MAA) is an attractive target for immunotherapy of @entity3 . We have recently generated a vaccine based on the HMW-MAA mimotope 225D9.2+ that was able to induce anti-HMW-MAA antibodies with antitumor activity in vitro. Here, we investigated the antitumor activity of these antibodies in a @entity0 @entity3 xenotransplant @entity4 ( @entity4 ) @entity2 model. EXPERIMENTAL DESIGN: @entity1 were established by injecting the @entity0 @entity3 518A2 cells into C.B.17 @entity4 / @entity4 @entity2 . In @entity1 prevention experiments, 200 microg purified total IgG antibodies were injected intravenously the same day or on day 5 in therapeutic experiments. Antibody administration was repeated every fourth day and @entity1 volumes were measured. Antibody specificity and @entity1 infiltration by macrophages were investigated by immunohistochemistry. RESULTS: Within 35 days after cell inoculation, antibody treatment reduced @entity1 growth up to 40% in the therapeutic and up to 62% in the @entity1 prevention experiments compared with the control @entity2 . In @entity1 of all groups, a similar distribution of the HMW-MAA and no differences in infiltration of macrophages were detected by immunohistochemistry. CONCLUSIONS: Here, we showed that antibodies induced by the 225D9.2+ mimotope effectively inhibited @entity3 growth. Additional mechanisms besides antibody-dependent cell cytotoxicity like disruption of interactions of @entity3 cells mediated by extracellular matrix components seem to be involved in @entity1 growth inhibition. Based on our findings, we suggest that active immunization with this mimotope might be a promising strategy for treatment of @entity3 .

title: Reduction of @entity0 @entity3 growth in @entity4 @entity2 by passive transfer of antibodies induced by a high molecular weight XXXX -associated antigen mimotope vaccine.

answer: @entity3


abstract: PURPOSE: The high molecular weight @entity3 -associated antigen (HMW-MAA) is an attractive target for immunotherapy of @entity3 . We have recently generated a vaccine based on the HMW-MAA mimotope 225D9.2+ that was able to induce anti-HMW-MAA antibodies with antitumor activity in vitro. Here, we investigated the antitumor activity of these antibodies in a @entity0 @entity3 xenotransplant @entity4 ( @entity4 ) @entity2 model. EXPERIMENTAL DESIGN: @entity1 were established by injecting the @entity0 @entity3 518A2 cells into C.B.17 @entity4 / @entity4 @entity2 . In @entity1 prevention experiments, 200 microg purified total IgG antibodies were injected intravenously the same day or on day 5 in therapeutic experiments. Antibody administration was repeated every fourth day and @entity1 volumes were measured. Antibody specificity and @entity1 infiltration by macrophages were investigated by immunohistochemistry. RESULTS: Within 35 days after cell inoculation, antibody treatment reduced @entity1 growth up to 40% in the therapeutic and up to 62% in the @entity1 prevention experiments compared with the control @entity2 . In @entity1 of all groups, a similar distribution of the HMW-MAA and no differences in infiltration of macrophages were detected by immunohistochemistry. CONCLUSIONS: Here, we showed that antibodies induced by the 225D9.2+ mimotope effectively inhibited @entity3 growth. Additional mechanisms besides antibody-dependent cell cytotoxicity like disruption of interactions of @entity3 cells mediated by extracellular matrix components seem to be involved in @entity1 growth inhibition. Based on our findings, we suggest that active immunization with this mimotope might be a promising strategy for treatment of @entity3 .

title: Reduction of @entity0 @entity3 growth in XXXX @entity2 by passive transfer of antibodies induced by a high molecular weight @entity3 -associated antigen mimotope vaccine.

answer: @entity4


abstract: PURPOSE: The high molecular weight @entity3 -associated antigen (HMW-MAA) is an attractive target for immunotherapy of @entity3 . We have recently generated a vaccine based on the HMW-MAA mimotope 225D9.2+ that was able to induce anti-HMW-MAA antibodies with antitumor activity in vitro. Here, we investigated the antitumor activity of these antibodies in a @entity0 @entity3 xenotransplant @entity4 ( @entity4 ) @entity2 model. EXPERIMENTAL DESIGN: @entity1 were established by injecting the @entity0 @entity3 518A2 cells into C.B.17 @entity4 / @entity4 @entity2 . In @entity1 prevention experiments, 200 microg purified total IgG antibodies were injected intravenously the same day or on day 5 in therapeutic experiments. Antibody administration was repeated every fourth day and @entity1 volumes were measured. Antibody specificity and @entity1 infiltration by macrophages were investigated by immunohistochemistry. RESULTS: Within 35 days after cell inoculation, antibody treatment reduced @entity1 growth up to 40% in the therapeutic and up to 62% in the @entity1 prevention experiments compared with the control @entity2 . In @entity1 of all groups, a similar distribution of the HMW-MAA and no differences in infiltration of macrophages were detected by immunohistochemistry. CONCLUSIONS: Here, we showed that antibodies induced by the 225D9.2+ mimotope effectively inhibited @entity3 growth. Additional mechanisms besides antibody-dependent cell cytotoxicity like disruption of interactions of @entity3 cells mediated by extracellular matrix components seem to be involved in @entity1 growth inhibition. Based on our findings, we suggest that active immunization with this mimotope might be a promising strategy for treatment of @entity3 .

title: Reduction of @entity0 @entity3 growth in @entity4 XXXX by passive transfer of antibodies induced by a high molecular weight @entity3 -associated antigen mimotope vaccine.

answer: @entity2


abstract: Hyaluronic acids (HA) grafted with @entity1 ( @entity2 ) ( @entity2 -g-HA) were synthesized. The materials characterization, enzymatic degradability and peptide (insulin) release from solutions of the copolymers were examined. Distribution of bioactive peptides within the polymer chain is well-known for combinations of @entity2 and polysaccharides as aqueous polymer two-phase systems. Insulin was preferentially partitioned into the @entity2 phase in a @entity2 /HA solution system. Enzymatic degradation of the copolymers was strongly dependent on the @entity2 content. Thermal analysis revealed that @entity2 -g-HA exhibited a variation in phase-separated structures depending on the @entity2 content. The solution of @entity2 -g-HA enabled insulin to remain in the @entity2 moieties dispersed in the HA matrix. Leakage of insulin from the copolymers was dependent upon the @entity2 content. Leakage rate of insulin from copolymer containing between 7 and 39% by weight of @entity2 were similar. A dramatic increase in leakage rate occurred when the @entity2 content was increased to greater than 39% by weight. It is considered that the loaded insulin was partitioned into the @entity2 moieties and became entangled with the @entity2 chains. The conformational change of insulin was effectively prevented in @entity2 -g-HA solutions, although insulin was denatured in storage of both @entity3 buffered solution and HA solution. Such a heterogeneous-structured polymeric solution may be advantageous as an injectable therapeutic formulation for ophthalmic or @entity0 treatment.

title: Hyaluronic acid grafted with XXXX as a novel peptide formulation.

answer: @entity1


abstract: @entity3 is a leading cause of death in France. Some of its risk factors are well identified such as age, smoking, @entity2 and @entity5 , but some others such as lipoprotein (a) ( @entity6 )) are still under investigation. @entity6 ) is an LDL-like particle to which is linked an apolipoprotein (a). The latter shows a high sequence homology with plasminogen that gives @entity6 ) thrombogenic properties in addition to its atherogenic capacity. Many epidemiological studies have shown that a high plasma level of @entity6 ) is a risk factor for coronary, cerebral and peripheral @entity4 . Out of thirteen prospective studies, ten have confirmed this result. The negative results from the three remaining studies were probably due to either the inadequate storage of the samples or the preventive drug treatment given to the @entity0 during the studies and to the lack of standardization of @entity6 ) assays. More over it has been shown that beside high plasma @entity6 ) level, the presence of a low molecular weight Apo(a) isoform is also related to a higher incidence of @entity3 . This review of the literature clearly demonstrates the relationship between @entity6 ) and @entity4 , and the need to measure @entity6 ) in order to better evaluate the risk of @entity4 especially in @entity0 with a hyper LDLemia an early cardio- or @entity1 or a family history of @entity4 . Management of @entity0 with high @entity6 ) concentrations should be directed at minimizing all other risk factors for @entity4 .

title: [Lipoprotein(a): risk factor for XXXX important to take into account in practice].

answer: @entity4


abstract: The aims of this study were: (1) to investigate the relationship between pre-delivery hemoglobin (Hb) concentration and the outcome of the pregnancy for the mother and @entity0 and (2) to assess the extent to which the pallor of the conjunctiva indicates severe @entity4 in pregnancy (Hb < 7 g/dl). We carried out a prospective study in 1995, in the maternity department of the National Sour   Sanou Hospital (Bobo-Dioulasso, Burkina Faso). @entity0 arriving to give birth at the maternity unit gave verbal consent and underwent a physical examination including the assessment of conjunctiva coloration. Finger-prick blood samples were taken from all the @entity0 selected and Hb was determined with a portable hemoglobin meter (HemoCue AB, Sweden). For each @entity0 , information about age, obstetric history, the condition of mother and @entity0 at admission and delivery and any post-delivery complications in the first 48 hours was collected before discharge from the maternity unit, 3 to 5 days after the delivery. @entity0 with @entity6 were excluded from the study and 247 @entity0 were included overall. Endometriosis was observed in only three cases. Three @entity0 died, two due to @entity3 . The third @entity0 died from @entity5 . The Hb concentrations of these @entity0 were 8 g/dl, 10.2 g/dl and 2.6 g/dl respectively. The mean Hb concentration for our population was 10.1 g/dl (SD = 2.08), with 165 @entity0 (67%) having less than 11 g Hb/dl. Forty-one @entity0 (17%) had less than 9 g Hb/dl and 16 (6%) had less than 7 g Hb/dl. Severe maternal @entity4 and pallor of the conjunctiva were significantly associated with pre-term delivery and perinatal @entity2 , but not with low birth weight. The sensitivity of the pallor of the conjunctiva for detection of severe maternal @entity4 was 87%, and its specificity was 88%. We found no evidence that maternal Hb levels of 9 to 10.9 g/dl were associated with a high risk of poor pregnancy outcome for either the mother or the @entity0 , although @entity0 with such levels of Hb are classed as anemic by the World Health Organization criteria. These results show that poor pregnancy outcome is associated with severe maternal @entity4 . Examination of the coloration of the conjunctiva is a suitable and affordable screening method for the detection of severe @entity4 . Mothers with severe @entity4 present with signs and symptoms of @entity4 and could therefore be given @entity1 treatment to improve their health. This demonstrates the importance of nutritional intervention during pregnancy.

title: [Assessing severe maternal XXXX and its consequences: the value of a simple examination of the coloration of palpebral conjunctiva].

answer: @entity4


abstract: OBJECTIVE: To assess the relationship between short sleep duration and @entity1 -related variables in @entity0 involved in the 'Qu  bec en Forme' Project. DESIGN: Cross-sectional study. SUBJECTS: A total of 422 @entity0 (211 @entity0 and 211 @entity0 ) aged between 5 and 10 years from primary schools in the City of Trois-Rivi  res (Qu  bec) were selected to participate in this study. MEASUREMENTS: Body weight, height and waist circumference were measured. The @entity0 were classified as normal, underweight, overweight or @entity1 , according to body mass index (BMI) per age. An exhaustive questionnaire was administered by telephone to the parents of @entity0 . RESULTS: The percentage of overweight/ @entity1 was 20.0% in @entity0 and 24.0% in @entity0 . When compared to @entity0 reporting 12-13 h of sleep per day, the adjusted odds ratio for childhood overweight/ @entity1 was 1.42 (95% confidence interval 1.09-1.98) for those with 10.5-11.5 h of sleep and 3.45 (2.61-4.67) for those with 8-10 h of sleep after adjustment for age, sex, and other risk factors. Parental @entity1 , low parental educational level, low total family income, long hours of TV watching, playing videogames or computer utilization, absence of breastfeeding and physical inactivity were also significantly associated with childhood overweight/ @entity1 . In addition, we observed a significant negative association adjusted for age between sleep duration and body weight (-0.33, P<0.01), BMI (-0.12, P<0.01) and waist circumference (-0.24, P<0.01) in @entity0 . CONCLUSION: An inverse association was observed between sleep duration and the risk to develop childhood overweight/ @entity1 . Longitudinal research will be required to confirm a potential link of causality between these variables.

title: Relationship between short sleeping hours and childhood overweight/ XXXX : results from the 'Qu  bec en Forme' Project.

answer: @entity1


abstract: INTRODUCTION: Studies that address sensitive topics, such as female @entity2 , often achieve poor response rates that can bias results. Factors that affect response rates to studies in this area are not well characterized. AIM: To model the response rate in studies investigating the prevalence of female @entity2 . Methods. Databases were searched for English-language, prevalence studies using the search terms: @entity2 , @entity0 / @entity0 /female, prevalence, and cross-sectional. Studies that did not report response rates or were clinic-based were excluded. A multiple linear regression model was constructed. MAIN OUTCOME MEASURES: Published response rates. RESULTS: A total of 1,380 publications were identified, and 54 of these met our inclusion criteria. Our model explained 58% of the variance in response rates of studies investigating the prevalence of difficulty with desire, arousal, orgasm, or @entity1 (R(2) = 0.581, P = 0.027). This model was based on study design variables, study year, location, and the reported prevalence of each type of sexual difficulty. More recent studies (beta = -1.05, P = 0.037) and studies that only included @entity0 over 50 years of age (beta = -31.11, P = 0.007) had lower response rates. The use of face-to-face interviews was associated with a higher response rate (beta = 20.51, P = 0.036). Studies that did not include questions regarding desire difficulties achieved higher response rates than those that did include questions on desire difficulty (beta = 23.70, P = 0.034). CONCLUSION: Response rates in prevalence studies addressing female @entity2 are frequently low and have decreased by an average of just over 1% per anum since the late 60s. Participation may improve by conducting interviews in @entity0 . Studies that investigate a broad range of ages may be less representative of older @entity0 , due to a poorer response in older age groups. Lower response rates in studies that investigate desire difficulty suggest that sexual desire is a particularly sensitive topic.

title: Modeling response rates in surveys of female XXXX .

answer: @entity2


abstract: INTRODUCTION: @entity4 ( @entity4 ) is a common cause of @entity2 . Therapeutic options target different @entity2 systems believed to be involved in its development and maintenance. Most treatments target the @entity2 component with the assumption that sexual function will increase once the @entity2 has decreased, yet this is not necessarily the case. AIMS: Research has supported the effectiveness of hypnosis for many @entity3 , and a case report demonstrated @entity2 reduction and an increase in intercourse pleasure in a @entity0 with @entity4 . This preliminary study examined the effectiveness of hypnosis on @entity2 and psychosexual function in @entity4 . METHODS; Eight @entity0 suffering from @entity4 completed a hypnosis screening assessment, an interview, @entity2 and psychosexual questionnaires, a gynecologic examination, @entity2 threshold measurement, a psychosexual assessment, and six hypnotherapy sessions. The physical examinations, interview, and questionnaires were repeated at 1 and 6 months posttreatment. MAIN OUTCOME MEASURES: These included @entity2 ratings during the gynecologic examination, @entity2 thresholds, scores on the McGill Pain Questionnaire and Pain Catastrophizing Scale, and responses to questions on intercourse-related and nonintercourse-related @entity2 . Measures of psychosexual function included the Female Sexual Function Index, State-Trait @entity1 Scale, Beck Depression Inventory-II, and the Brief Symptom Inventory. RESULTS: Results indicated significant decreases in gynecologic examination @entity2 and in several measures assessing intercourse @entity2 , and nonsignificant increases in threshold. Some indices of noncoital @entity2 decreased. Overall sexual function, particularly sexual satisfaction, increased at posttreatment. There were no differences on any psychological measure. @entity0 reported satisfaction with the treatment and rated their @entity2 reduction as average. CONCLUSIONS: Hypnotherapy appears to be a promising treatment for reducing intercourse @entity2 and some aspects of noncoital @entity2 , and for restoring sexual function in @entity0 with @entity4 . These results suggest that a large controlled trial should be considered.

title: Effectiveness of hypnosis for the treatment of XXXX : a preliminary investigation.

answer: @entity4


abstract: BACKGROUND: Data from experimental studies suggest that @entity5 , the long acting @entity4 analogue, improves survival of animals with @entity3 . To assess the antitumour effect of @entity5 , a randomized trial was performed comparing @entity5 with supportive care in advanced @entity3 @entity0 . All @entity0 , aged 59-75 years, were not liable to radical surgical treatment and were not submitted to other treatments (chemo and/or radiotherapy). METHODS: Six @entity0 were enrolled, 4 of these treated with @entity5 (500 micrograms two times a day subcutaneous for six months) and the other 2 were inserted a control group. RESULTS: The @entity0 treated with @entity5 showed a significant advantage in quality of life (restored appetite, improvement of digestion and intestine function, remission of @entity2 and preservation of baseline body weight) with a mean > 80 of karnofsky performance score. Monitoring of @entity1 size changes (US-TC) over the 6 months study period, showed slackened @entity1 in all treated @entity0 , whereas @entity1 grew according to an almost exponential trend in untreated @entity0 . Also survival was better in treated @entity0 : in particular, 2 @entity0 out of 4 who completed the study underwent follow-up until they died 12 and 16 months after beginning of treatment, respectively. Karnofsky performance score was particularly high in both @entity0 . This supports the view that @entity5 is endowed with antiproliferative activity. CONCLUSION: In conclusion @entity5 therapy seems to confer a survival benefit and a better quality of life in advanced @entity1 . Additional studies are needed to confirm these results and to clarify other questions about dose and @entity4 receptors in this kind of @entity1 .

title: [ @entity5 in the treatment of advanced XXXX . Preliminary study].

answer: @entity3


abstract: BACKGROUND: Data from experimental studies suggest that @entity5 , the long acting @entity4 analogue, improves survival of animals with @entity3 . To assess the antitumour effect of @entity5 , a randomized trial was performed comparing @entity5 with supportive care in advanced @entity3 @entity0 . All @entity0 , aged 59-75 years, were not liable to radical surgical treatment and were not submitted to other treatments (chemo and/or radiotherapy). METHODS: Six @entity0 were enrolled, 4 of these treated with @entity5 (500 micrograms two times a day subcutaneous for six months) and the other 2 were inserted a control group. RESULTS: The @entity0 treated with @entity5 showed a significant advantage in quality of life (restored appetite, improvement of digestion and intestine function, remission of @entity2 and preservation of baseline body weight) with a mean > 80 of karnofsky performance score. Monitoring of @entity1 size changes (US-TC) over the 6 months study period, showed slackened @entity1 in all treated @entity0 , whereas @entity1 grew according to an almost exponential trend in untreated @entity0 . Also survival was better in treated @entity0 : in particular, 2 @entity0 out of 4 who completed the study underwent follow-up until they died 12 and 16 months after beginning of treatment, respectively. Karnofsky performance score was particularly high in both @entity0 . This supports the view that @entity5 is endowed with antiproliferative activity. CONCLUSION: In conclusion @entity5 therapy seems to confer a survival benefit and a better quality of life in advanced @entity1 . Additional studies are needed to confirm these results and to clarify other questions about dose and @entity4 receptors in this kind of @entity1 .

title: [ XXXX in the treatment of advanced @entity3 . Preliminary study].

answer: @entity5


abstract: The objective of this study was to investigate potential for @entity2 ( @entity2 ) using a newly developed, geometrically detailed, finite element head model (FEHM) within the concept of a simulated injury monitor (SIMon). The new FEHM is comprised of several parts: cerebrum, cerebellum, falx, tentorium, combined pia-arachnoid complex (PAC) with cerebro-spinal fluid (CSF), ventricles, brainstem, and parasagittal blood vessels. The model's topology was derived from @entity0 computer tomography (CT) scans and then uniformly scaled such that the mass of the brain represents the mass of a 50th percentile male's brain (1.5 kg) with the total head mass of 4.5 kg. The topology of the model was then compared to the preliminary data on the average topology derived from Procrustes shape analysis of 59 individuals. Material properties of the various parts were assigned based on the latest experimental data. After rigorous validation of the model using neutral density targets (NDT) and pressure data, the stability of FEHM was tested by loading it simultaneously with translational (up to 400 g) combined with rotational (up to 24,000 rad/s2) acceleration pulses in both sagittal and coronal planes. Injury criteria were established in the manner shown in Takhounts et al. (2003a). After thorough validation and injury criteria establishment (cumulative strain damage measure--CSDM for @entity1 ( @entity1 ), relative motion damage measure--RMDM for @entity4 ( @entity4 ), and dilatational damage measure--DDM for contusions and focal lesions), the model was used in investigation of mild @entity2 cases in living @entity0 based on a set of head impact data taken from American football players at the collegiate level. It was found that CSDM and especially RMDM correlated well with angular acceleration and angular velocity. DDM was close to zero for most impacts due to their mild severity implying that cavitational pressure anywhere in the brain was not reached. Maximum principal strain was found to correlate well with RMDM and angular head kinematic measures. Maximum principal stress didn't correlate with any kinematic measure or injury metric. The model was then used in the investigation of @entity3 potential in NHTSA conducted side impact tests. It was also used in parametric investigations of various "what if" scenarios, such as side versus frontal impact, to establish a potential link between head kinematics and injury outcomes. The new SIMon FEHM offers an advantage over the previous version because it is geometrically more representative of the @entity0 head. This advantage, however, is made possible at the expense of additional computational time.

title: Investigation of XXXX using the next generation of simulated injury monitor (SIMon) finite element head model.

answer: @entity2


abstract: Phosphodiesterases are enzymes that catalyze the degradation of the @entity6 , @entity3 and @entity5 , to the corresponding 5' @entity1 monophosphates. Ten different phosphodiesterase families have been described to date. These enzymes exist as homodimers and there is structural similarity between the different families. However, they differ in several respects like selectivity for @entity6 , sensitivity for inhibitors and activators, physiological roles and tissue distribution. Interest in these enzymes has increased tremendously, both within the medical community and in the general public as a consequence of @entity4 (Viagra), the medication recently introduced for the treatment of @entity0 . @entity4 mediates its effects by inhibiting phosphodiesterase 5. Some biochemical and molecular biological aspects of this enzyme are presented here. To achieve satisfactory erection, normal penile innervation is required. @entity2 , the transmitter substance in these nerves, activates guanylyl cyclase, thereby increasing @entity5 production. The increased levels of @entity5 cause relaxation of smooth muscles in penile vessels and this leads to an erection. Erection is dependent on elevated levels of @entity5 and @entity4 mediates its effects by inhibiting the degradation of @entity5 . Other functions that are mediated by the phosphodiesterases explain visual disturbances, flushing and decreased blood pressure that are some of the side effects seen with @entity4 treatment. Furthermore, the potentially fatal consequence of combining @entity4 and nitrovasodilators is discussed.

title: [Phosphodiesterase 5--the enzyme inhibited by XXXX (Viagra)].

answer: @entity4


abstract: The case of a 55-year-old @entity0 with postpartum (at age of 22) @entity7 is reported. The @entity0 , with signs of @entity6 , was admitted to a @entity1 hospital for @entity5 . In addition to routine tests and measurements of thyroid hormones level, magnetic resonance imaging (MRI) of the brain and pituitary region was performed. The results of MRI showed @entity2 and a @entity8 ". On the basis of clinical, laboratory and instrumental data, a diagnosis of @entity9 with @entity4 was achieved. Many hypotheses could be made regarding its pathogenesis. Initially we considered the diagnosis of @entity7 in which the sella turcica usually presents normal or reduced dimensions. However the presence of a @entity8 " with thin walls, excludes this diagnosis. The delay of menarche and the short stature suggest the hypothesis of a preexistent pathological condition. It is possible that the @entity0 had liquefied pituitary @entity3 as a consequence of the postpartum shock or that she was @entity4 , a condition in which the " @entity8 " is very common.

title: [ XXXX in adults: a magnetic resonance study of cerebral and hypophyseal changes].

answer: @entity4


abstract: BACKGROUND: Thoracentesis and antibiotics remain the cornerstones of treatment in stage I @entity5 . The management of disease progression or late presentation is controversial. Open thoracotomy and decortication is perceived to be synonymous with protracted recovery and prolonged hospitalisation. Advocates of thoracoscopic adhesiolysis cite earlier chest drain removal and hospital discharge. This paper challenges traditional prejudice towards open surgery. METHODS: A five year audit of @entity5 cases referred to a regional cardiothoracic surgical unit analysing previous clinical course, surgical management, and outcome. RESULTS: Between February 1992 and February 1997, the number of referrals to this centre increased dramatically. Twenty-two @entity0 were referred for surgery (15 @entity0 , seven @entity0 ; age range, 0.5-16 years). Before referral, @entity0 had been unwell for 6-50 days (median, 15), had been treated with several antibiotics, and had undergone chest ultrasound (15 @entity0 ), computed tomography (five @entity0 ), @entity4 (13 @entity0 ), and intercostal drainage (seven @entity0 ). The organism responsible was identified in only two cases ( @entity3 ). Three @entity0 had intraparenchymal abscess formation. Eighteen @entity0 underwent open thoracotomy and decortication. Drain removal was performed on the first or second day. @entity2 resolved within 48 hours. Median hospital stay was four days. All @entity0 had complete clinical and radiological resolution. CONCLUSIONS: Treatment must be tailored to the disease stage. In @entity1 , open decortication followed by early drain removal results in rapid symptomatic recovery, early hospital discharge, and complete resolution. In the early fibrinopurulent phase, alternative strategies should be considered. However, even in ideal cases, neither fibrinolysis nor thoracoscopic adhesiolysis can achieve more rapid resolution at lower risk.

title: XXXX : a role for open thoracotomy and decortication.

answer: @entity5


abstract: BACKGROUND: Childhood physical inactivity and @entity1 are serious public health threats. Socioecological approaches to addressing these threats have been proposed. The school is a critical environment for promoting @entity0 's health and provides the opportunity to explore the impact of a socioecological approach. CONTEXT: Thirty percent of @entity0 in British Columbia, Canada, are overweight or @entity1 , and 50% of youths are not physically active enough to yield health benefits. METHODS: Action Schools! BC, a socioecological model, was developed to create 1) an elementary school environment where students are provided with more opportunities to make healthy choices and 2) a supportive community and provincial environment to facilitate change at the school and individual levels. CONSEQUENCES: The environment in British Columbia for school- and provincial-level action on health behaviors improved. Focus group and project tracking results indicated that the Action Schools! BC model enhanced the conceptual use of knowledge and was an influencing factor. Political will and public interest were also cited as influential factors. INTERPRETATION: The Action Schools! BC model required substantial and demanding changes in the approach of the researchers, policy makers, and support team toward health promotion. Despite challenges, Action Schools! BC provides a good example of how to enhance knowledge exchange and multilevel intersectoral action in @entity2 prevention.

title: Action Schools! BC: a socioecological approach to modifying XXXX risk factors in elementary school @entity0 .

answer: @entity2


abstract: BACKGROUND: Childhood physical inactivity and @entity1 are serious public health threats. Socioecological approaches to addressing these threats have been proposed. The school is a critical environment for promoting @entity0 's health and provides the opportunity to explore the impact of a socioecological approach. CONTEXT: Thirty percent of @entity0 in British Columbia, Canada, are overweight or @entity1 , and 50% of youths are not physically active enough to yield health benefits. METHODS: Action Schools! BC, a socioecological model, was developed to create 1) an elementary school environment where students are provided with more opportunities to make healthy choices and 2) a supportive community and provincial environment to facilitate change at the school and individual levels. CONSEQUENCES: The environment in British Columbia for school- and provincial-level action on health behaviors improved. Focus group and project tracking results indicated that the Action Schools! BC model enhanced the conceptual use of knowledge and was an influencing factor. Political will and public interest were also cited as influential factors. INTERPRETATION: The Action Schools! BC model required substantial and demanding changes in the approach of the researchers, policy makers, and support team toward health promotion. Despite challenges, Action Schools! BC provides a good example of how to enhance knowledge exchange and multilevel intersectoral action in @entity2 prevention.

title: Action Schools! BC: a socioecological approach to modifying @entity2 risk factors in elementary school XXXX .

answer: @entity0


abstract: STUDY OBJECTIVE: To estimate the occurrence of @entity1 and @entity2 in @entity3 in @entity0 with and without symptoms. DESIGN: Retrospective registration of all @entity0 who underwent hysteroscopic resection of @entity3 . Age, menopausal status, presence or absence of symptoms, any use of hormonal medication, as well as histologic diagnosis, complications, and eventual repeated surgery were documented (Canadian Task Force classification II-3). SETTING: Ullevaal University Hospital, Department of Gynecology. @entity0 : All @entity0 who underwent hysteroscopic resection of an endometrial polyp in our department from January 1, 2001 through @entity4 , 2005. INTERVENTIONS: Hysteroscopic resection of @entity3 . MEASUREMENTS AND MAIN RESULTS: Four hundred eleven @entity0 were included. One hundred twenty-nine @entity0 (31.4%) had no symptoms. The prevalence of @entity1 or @entity2 was 3.2% in @entity0 with symptoms and 3.9% in those without symptoms. CONCLUSION: The prevalence of @entity1 and @entity2 was found to be relatively high, indicating that symptomatic, as well as asymptomatic, @entity3 should be removed.

title: Hysteroscopic resection of symptomatic and asymptomatic XXXX .

answer: @entity3


abstract: PURPOSE: To phenotype a family with RHO ( @entity3 or @entity3 ) @entity1 ( @entity2 ) and to describe an approach to surveying affected families. METHODS: Four @entity0 from a family with a history of autosomal dominant @entity2 had complete clinical examinations and underwent full-field electroretinography (ERG), fundus autofluorescence (AF) imaging, and genetic testing. One @entity0 had microperimetry (MP) mapping. RESULTS: The @entity0 ' ages ranged from 6 years to 47 years. The proband, the father, had fundoscopic findings typical of @entity2 . A small hyperfluorescent ring centered at the fovea was apparent on AF. MP showed preservation of central 7 degrees of visual field within this ring. The three @entity0 were all asymptomatic with visual acuity of 20/15 in each eye. One @entity0 had mild retinal pigment epithelium migration on fundoscopy; the other two @entity0 had normal fundoscopic examinations. Two @entity0 showed increased parafoveal AF. In the two affected @entity0 , average ERG b-wave implicit times were delayed in scotopic conditions, and maximal ERG tracings had abnormal waveforms. Genetic analysis confirmed that two of three asymptomatic @entity0 carried the @entity3 allele. CONCLUSIONS: @entity0 with RHO ( @entity3 ) @entity2 ( @entity2 ) can show classic signs of @entity2 on fundus examination and may be able to maintain good central visual acuity into adulthood. By combining clinical examination with AF imaging and electrophysiology, it is possible to offer presymptomatic clinical evaluation to families with this @entity2 .

title: Phenotype-genotype correlations in XXXX caused by RHO, @entity3 .

answer: @entity2


abstract: PURPOSE: To phenotype a family with RHO ( @entity3 or @entity3 ) @entity1 ( @entity2 ) and to describe an approach to surveying affected families. METHODS: Four @entity0 from a family with a history of autosomal dominant @entity2 had complete clinical examinations and underwent full-field electroretinography (ERG), fundus autofluorescence (AF) imaging, and genetic testing. One @entity0 had microperimetry (MP) mapping. RESULTS: The @entity0 ' ages ranged from 6 years to 47 years. The proband, the father, had fundoscopic findings typical of @entity2 . A small hyperfluorescent ring centered at the fovea was apparent on AF. MP showed preservation of central 7 degrees of visual field within this ring. The three @entity0 were all asymptomatic with visual acuity of 20/15 in each eye. One @entity0 had mild retinal pigment epithelium migration on fundoscopy; the other two @entity0 had normal fundoscopic examinations. Two @entity0 showed increased parafoveal AF. In the two affected @entity0 , average ERG b-wave implicit times were delayed in scotopic conditions, and maximal ERG tracings had abnormal waveforms. Genetic analysis confirmed that two of three asymptomatic @entity0 carried the @entity3 allele. CONCLUSIONS: @entity0 with RHO ( @entity3 ) @entity2 ( @entity2 ) can show classic signs of @entity2 on fundus examination and may be able to maintain good central visual acuity into adulthood. By combining clinical examination with AF imaging and electrophysiology, it is possible to offer presymptomatic clinical evaluation to families with this @entity2 .

title: Phenotype-genotype correlations in @entity2 caused by RHO, XXXX .

answer: @entity3


abstract: BACKGROUND: Platelet production is regulated by a thrombopoietic growth factor ( @entity8 ). The receptor for this platelet growth factor ( @entity7 ) is expressed on the platelet surface membrane. A recombinant thrombopoietic cytokine, recombinant @entity0 @entity8 coupled with @entity3 ( @entity4 -rHuMGDF), was added to apheresis platelets in vitro to determine whether @entity7 ligand-receptor binding produced any beneficial or adverse effect on the development of the platelet storage lesion during 5 days of storage. STUDY DESIGN AND METHODS: This study was designed as a dose-response protocol to determine the effects of adding increasing concentrations of @entity9 (0.0 [control], 2.5, 25, and 250 ng/mL) to apheresis platelets stored in two types of plastic storage containers. The increasing concentrations of @entity4 -rHuMGDF used simulated the theoretical peak plasma level attained in vivo, with an intravenous dose of 0, 0.1, 1.0 and 10 microg per kg of @entity4 -rHuMGDF. The platelets were stored with agitation at 20 to 24 degrees C for 5 days. A battery of in vitro assays was performed on storage Days 1 and 5, including pH, blood gases, platelet count, @entity2 dehydrogenase, mean platelet volume, @entity1 , @entity2 , osmotic recovery, morphology score, @entity6 , and one-dimensional @entity5 gel electrophoresis analyses. RESULTS: Analysis of results on both Day 1 and Day 5 showed no significant differences among any of the three @entity4 -rHuMGDF doses and the control group, for any in vitro assay. One-dimensional @entity5 gel electrophoresis showed no changes among the platelet protein patterns for the three @entity4 -rHuMGDF doses studied or the control. Storage-induced changes, however, did occur equally in all four groups of platelets over the 5 days of storage. CONCLUSION: The addition to stored apheresis platelets of up to 10 microg per kg of @entity4 -rHuMGDF (250 ng/mL), followed by 5 days of storage at standard conditions, does not appear to promote or retard development of the platelet storage lesion.

title: Effect of recombinant @entity0 XXXX coupled with @entity3 on the platelet storage lesion.

answer: @entity8


abstract: BACKGROUND: Platelet production is regulated by a thrombopoietic growth factor ( @entity8 ). The receptor for this platelet growth factor ( @entity7 ) is expressed on the platelet surface membrane. A recombinant thrombopoietic cytokine, recombinant @entity0 @entity8 coupled with @entity3 ( @entity4 -rHuMGDF), was added to apheresis platelets in vitro to determine whether @entity7 ligand-receptor binding produced any beneficial or adverse effect on the development of the platelet storage lesion during 5 days of storage. STUDY DESIGN AND METHODS: This study was designed as a dose-response protocol to determine the effects of adding increasing concentrations of @entity9 (0.0 [control], 2.5, 25, and 250 ng/mL) to apheresis platelets stored in two types of plastic storage containers. The increasing concentrations of @entity4 -rHuMGDF used simulated the theoretical peak plasma level attained in vivo, with an intravenous dose of 0, 0.1, 1.0 and 10 microg per kg of @entity4 -rHuMGDF. The platelets were stored with agitation at 20 to 24 degrees C for 5 days. A battery of in vitro assays was performed on storage Days 1 and 5, including pH, blood gases, platelet count, @entity2 dehydrogenase, mean platelet volume, @entity1 , @entity2 , osmotic recovery, morphology score, @entity6 , and one-dimensional @entity5 gel electrophoresis analyses. RESULTS: Analysis of results on both Day 1 and Day 5 showed no significant differences among any of the three @entity4 -rHuMGDF doses and the control group, for any in vitro assay. One-dimensional @entity5 gel electrophoresis showed no changes among the platelet protein patterns for the three @entity4 -rHuMGDF doses studied or the control. Storage-induced changes, however, did occur equally in all four groups of platelets over the 5 days of storage. CONCLUSION: The addition to stored apheresis platelets of up to 10 microg per kg of @entity4 -rHuMGDF (250 ng/mL), followed by 5 days of storage at standard conditions, does not appear to promote or retard development of the platelet storage lesion.

title: Effect of recombinant @entity0 @entity8 coupled with XXXX on the platelet storage lesion.

answer: @entity3


abstract: BACKGROUND: Platelet production is regulated by a thrombopoietic growth factor ( @entity8 ). The receptor for this platelet growth factor ( @entity7 ) is expressed on the platelet surface membrane. A recombinant thrombopoietic cytokine, recombinant @entity0 @entity8 coupled with @entity3 ( @entity4 -rHuMGDF), was added to apheresis platelets in vitro to determine whether @entity7 ligand-receptor binding produced any beneficial or adverse effect on the development of the platelet storage lesion during 5 days of storage. STUDY DESIGN AND METHODS: This study was designed as a dose-response protocol to determine the effects of adding increasing concentrations of @entity9 (0.0 [control], 2.5, 25, and 250 ng/mL) to apheresis platelets stored in two types of plastic storage containers. The increasing concentrations of @entity4 -rHuMGDF used simulated the theoretical peak plasma level attained in vivo, with an intravenous dose of 0, 0.1, 1.0 and 10 microg per kg of @entity4 -rHuMGDF. The platelets were stored with agitation at 20 to 24 degrees C for 5 days. A battery of in vitro assays was performed on storage Days 1 and 5, including pH, blood gases, platelet count, @entity2 dehydrogenase, mean platelet volume, @entity1 , @entity2 , osmotic recovery, morphology score, @entity6 , and one-dimensional @entity5 gel electrophoresis analyses. RESULTS: Analysis of results on both Day 1 and Day 5 showed no significant differences among any of the three @entity4 -rHuMGDF doses and the control group, for any in vitro assay. One-dimensional @entity5 gel electrophoresis showed no changes among the platelet protein patterns for the three @entity4 -rHuMGDF doses studied or the control. Storage-induced changes, however, did occur equally in all four groups of platelets over the 5 days of storage. CONCLUSION: The addition to stored apheresis platelets of up to 10 microg per kg of @entity4 -rHuMGDF (250 ng/mL), followed by 5 days of storage at standard conditions, does not appear to promote or retard development of the platelet storage lesion.

title: Effect of recombinant XXXX @entity8 coupled with @entity3 on the platelet storage lesion.

answer: @entity0


abstract: Obesity has emerged as one of the most complex and @entity3 affecting the world's population. It is estimated that more than two thirds of Americans are overweight and more than 20% are @entity2 . This disease is associated with many morbid conditions, including @entity4 , @entity7 , @entity8 , @entity6 , @entity1 , and an increased incidence of certain @entity0 . Medical interventions for achieving and maintaining significant @entity5 have generally failed, leaving surgery as the only effective treatment for durable @entity5 . A number of surgical options are available today and can be grouped into two categories based on the mechanism of how the @entity5 is achieved. Restrictive procedures include vertical banded gastroplasty (VBG), adjustable gastric banding (AGB), and Roux-en-Y gastric bypass (RYGB), although the latter does have some altered absorption as well. Largely malabsorptive procedures include biliopancreatic diversion (BPD) and biliopancreatic diversion with duodenal switch (BPD-DS). Whereas VBG has largely fallen out of favor due to inadequate long-term @entity5 , the other procedures have proven successful in achieving and maintaining adequate @entity5 . In addition, each has proven successful in reversing or ameliorating many of the comorbidities associated with @entity2 . RYGB is the most common procedure performed in the United States and is considered the gold standard. It has the best short- and long-term results for safety, efficacy, and durability, and it has been proven to be superior in results to those for AGB. In experienced hands, this technically challenging procedure can now be performed laparoscopically. This method has the same @entity5 and health benefits as the open procedure while achieving all the added benefits of a minimally invasive approach. Long-term data seem to support the malabsorptive procedures as most effective in the superobese. All the procedures require compliance and long-term nutritional follow-up.

title: Surgical treatment of XXXX .

answer: @entity2


abstract: The effect of the non-peptide selective tachykinin @entity7 antagonist @entity6 has been investigated on @entity0 formation and neutrophil accumulation induced by @entity2 (50 degrees C for 5 min), mustard oil, substance P, the tachykinin NK1 agonist @entity8 , and @entity3 in the abdominal skin of the anaesthetised @entity1 . @entity6 significantly inhibited (120 nmol/kg i.v.) or prevented (240 nmol/kg i.v.) the early @entity0 formation (0-10 min) induced by @entity2 . However, a dosing strategy which blocked NK1 receptors for 5 h ( @entity6 , 240 nmol/kg i.v. + 240 nmol/kg s.c.) failed to influence neutrophil accumulation measured 5 h after @entity2 . Thus, the neurogenic component mediated by NK1 receptors is important to elicit the early @entity0 formation, but does not influence subsequent neutrophil accumulation. Topical application of mustard oil (2%), a @entity5 stimulant, caused @entity7 -mediated early neurogenic plasma extravasation, but did not induce cutaneous neutrophil accumulation over 5 h. Substance P and @entity8 at high doses (1 nmol/site) also failed to elicit neutrophil accumulation. Neutrophil accumulation induced by @entity3 (0.03-3 pmol i.d.) was not affected by @entity6 pretreatment. In conclusion, despite an early pronounced tachykinin @entity7 -dependent @entity0 response after @entity2 , the results suggest that subsequent neutrophil accumulation is not mediated by NK1 receptors. Furthermore, we have not obtained any evidence to suggest that either endogenous or exogenous @entity4 can directly induce neutrophil accumulation in the @entity1 cutaneous microvasculature.

title: Lack of evidence for XXXX @entity7 -mediated neutrophil accumulation in the @entity1 cutaneous microvasculature by @entity2 .

answer: @entity4


abstract: The effect of the non-peptide selective tachykinin @entity7 antagonist @entity6 has been investigated on @entity0 formation and neutrophil accumulation induced by @entity2 (50 degrees C for 5 min), mustard oil, substance P, the tachykinin NK1 agonist @entity8 , and @entity3 in the abdominal skin of the anaesthetised @entity1 . @entity6 significantly inhibited (120 nmol/kg i.v.) or prevented (240 nmol/kg i.v.) the early @entity0 formation (0-10 min) induced by @entity2 . However, a dosing strategy which blocked NK1 receptors for 5 h ( @entity6 , 240 nmol/kg i.v. + 240 nmol/kg s.c.) failed to influence neutrophil accumulation measured 5 h after @entity2 . Thus, the neurogenic component mediated by NK1 receptors is important to elicit the early @entity0 formation, but does not influence subsequent neutrophil accumulation. Topical application of mustard oil (2%), a @entity5 stimulant, caused @entity7 -mediated early neurogenic plasma extravasation, but did not induce cutaneous neutrophil accumulation over 5 h. Substance P and @entity8 at high doses (1 nmol/site) also failed to elicit neutrophil accumulation. Neutrophil accumulation induced by @entity3 (0.03-3 pmol i.d.) was not affected by @entity6 pretreatment. In conclusion, despite an early pronounced tachykinin @entity7 -dependent @entity0 response after @entity2 , the results suggest that subsequent neutrophil accumulation is not mediated by NK1 receptors. Furthermore, we have not obtained any evidence to suggest that either endogenous or exogenous @entity4 can directly induce neutrophil accumulation in the @entity1 cutaneous microvasculature.

title: Lack of evidence for @entity4 @entity7 -mediated neutrophil accumulation in the @entity1 cutaneous microvasculature by XXXX .

answer: @entity2


abstract: The effect of the non-peptide selective tachykinin @entity7 antagonist @entity6 has been investigated on @entity0 formation and neutrophil accumulation induced by @entity2 (50 degrees C for 5 min), mustard oil, substance P, the tachykinin NK1 agonist @entity8 , and @entity3 in the abdominal skin of the anaesthetised @entity1 . @entity6 significantly inhibited (120 nmol/kg i.v.) or prevented (240 nmol/kg i.v.) the early @entity0 formation (0-10 min) induced by @entity2 . However, a dosing strategy which blocked NK1 receptors for 5 h ( @entity6 , 240 nmol/kg i.v. + 240 nmol/kg s.c.) failed to influence neutrophil accumulation measured 5 h after @entity2 . Thus, the neurogenic component mediated by NK1 receptors is important to elicit the early @entity0 formation, but does not influence subsequent neutrophil accumulation. Topical application of mustard oil (2%), a @entity5 stimulant, caused @entity7 -mediated early neurogenic plasma extravasation, but did not induce cutaneous neutrophil accumulation over 5 h. Substance P and @entity8 at high doses (1 nmol/site) also failed to elicit neutrophil accumulation. Neutrophil accumulation induced by @entity3 (0.03-3 pmol i.d.) was not affected by @entity6 pretreatment. In conclusion, despite an early pronounced tachykinin @entity7 -dependent @entity0 response after @entity2 , the results suggest that subsequent neutrophil accumulation is not mediated by NK1 receptors. Furthermore, we have not obtained any evidence to suggest that either endogenous or exogenous @entity4 can directly induce neutrophil accumulation in the @entity1 cutaneous microvasculature.

title: Lack of evidence for @entity4 XXXX -mediated neutrophil accumulation in the @entity1 cutaneous microvasculature by @entity2 .

answer: @entity7


abstract: The effect of the non-peptide selective tachykinin @entity7 antagonist @entity6 has been investigated on @entity0 formation and neutrophil accumulation induced by @entity2 (50 degrees C for 5 min), mustard oil, substance P, the tachykinin NK1 agonist @entity8 , and @entity3 in the abdominal skin of the anaesthetised @entity1 . @entity6 significantly inhibited (120 nmol/kg i.v.) or prevented (240 nmol/kg i.v.) the early @entity0 formation (0-10 min) induced by @entity2 . However, a dosing strategy which blocked NK1 receptors for 5 h ( @entity6 , 240 nmol/kg i.v. + 240 nmol/kg s.c.) failed to influence neutrophil accumulation measured 5 h after @entity2 . Thus, the neurogenic component mediated by NK1 receptors is important to elicit the early @entity0 formation, but does not influence subsequent neutrophil accumulation. Topical application of mustard oil (2%), a @entity5 stimulant, caused @entity7 -mediated early neurogenic plasma extravasation, but did not induce cutaneous neutrophil accumulation over 5 h. Substance P and @entity8 at high doses (1 nmol/site) also failed to elicit neutrophil accumulation. Neutrophil accumulation induced by @entity3 (0.03-3 pmol i.d.) was not affected by @entity6 pretreatment. In conclusion, despite an early pronounced tachykinin @entity7 -dependent @entity0 response after @entity2 , the results suggest that subsequent neutrophil accumulation is not mediated by NK1 receptors. Furthermore, we have not obtained any evidence to suggest that either endogenous or exogenous @entity4 can directly induce neutrophil accumulation in the @entity1 cutaneous microvasculature.

title: Lack of evidence for @entity4 @entity7 -mediated neutrophil accumulation in the XXXX cutaneous microvasculature by @entity2 .

answer: @entity1


abstract: OBJECTIVE: Virilization due to @entity2 -secreting @entity1 in @entity0 is a result of @entity2 overproduction from benign or @entity1 that are found in the ovaries or rarely in the adrenal glands. @entity1 that arise from ectopic adrenal tissue are extremely rare. We describe a very rare case of an ectopic @entity2 -producing @entity1 . DESIGN: Case report study. SETTING: Endocrinology outpatient department of university-affiliated teaching hospital. @entity0 (S): A 45-year-old @entity0 with symptoms of virilization of abrupt onset and rapid progression, with high serum @entity2 hormone levels and normal glucocorticoid secretion. INTERVENTION(S): Basal hormonal levels, stimulation and suppression tests, imaging techniques, and selective venous sampling. MAIN OUTCOME MEASURE(S): Localization and surgical removal of the source of @entity2 production. RESULT(S): An ectopic mass was detected behind the left iliopsoas muscle. The @entity0 was operated on and an oblong-shaped lesion, weighing 6 g, was removed. Histologically, the tissue was identified to be of adrenal origin. Postoperatively the @entity2 levels decreased to normal levels. CONCLUSION(S): This case illustrates difficulties in detecting and localizing the rare contingence of an ectopic adrenocortical @entity2 -secreting @entity1 .

title: Virilization caused by an ectopic XXXX located behind the iliopsoas muscle.

answer: @entity1


abstract: BACKGROUND: Few studies have evaluated exhaled NO measurement during @entity3 . OBJECTIVES: To evaluate exhaled NO fraction (FE(NO)) and peak expiratory flow (PEF) time-courses during @entity3 treatment ( @entity5 -agonist plus systemic @entity1 ) and to assess whether FE(NO) time-course predicts subsequent @entity2 control. METHODS: Sixty-five @entity4 @entity0 (mean +/- SD, 34 +/- 10 years) were prospectively enrolled in three Emergency Departments. RESULTS: Sixteen @entity0 were excluded (failure of offline FE(NO) measurement at 100 mL/s [FE(NO 0.1)], n = 4, and early discharge). The 49 remaining @entity0 performed FE(NO 0.1) and PEF on admission, at the 2nd (H2) and 6th hour (H6). Follow-up using an Asthma Control Diary was obtained in 27 of 49 @entity0 , whether they were hospitalized (n = 9) or discharged (n = 18). All but 2 @entity0 had elevated FE(NO) on admission (median [interquartile], 49 [26-78] ppb). Unlike PEF, mean FE(NO 0.1) of our sample was not significantly modified by treatment. No significant relationship was evidenced between exhaled NO and PEF variations. The variation of FE(NO 0.1) [H0 minus H6] was different in @entity0 who were hospitalized (decrease of 8 +/- 20 ppb) versus discharged (increase of 5 +/- 20 ppb, p = 0.04). This variation of FE(NO 0.1) was correlated with the Diary score (control of subsequent week), an initial increase in FE(NO 0.1) being associated with better @entity2 control. Nevertheless, neither exhaled NO nor PEFR were good predictors of @entity2 control. CONCLUSIONS: An increase in FE(NO) is observed in almost all @entity0 with @entity3 , and its subsequent increase within 6 hours is associated with a better degree of @entity2 control in the subsequent week.

title: Offline exhaled nitric oxide in emergency department and subsequent XXXX control.

answer: @entity3


abstract: OBJECTIVE: To review the pharmacology, efficacy, and safety of vorapaxar, a @entity12 ( @entity12 ) antagonist, in the management of @entity8 . DATA SOURCES: Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist. STUDY SELECTION AND DATA EXTRACTION: A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions). DATA SYNTHESIS: Two phase III clinical trials with vorapaxar have been published. In @entity0 with non-ST segment elevation @entity6 ( @entity6 ), vorapaxar failed to significantly reduce the primary efficacy end point (composite of @entity3 , @entity6 , @entity2 , recurrent @entity1 with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for @entity0 with @entity3 , the composite end point of @entity3 , @entity6 , or @entity2 was significantly reduced. In both trials, the safety end points of major/minor @entity5 were increased compared with placebo. In the secondary prevention trial, an increased incidence of @entity9 led to the exclusion of @entity0 with a prior history of @entity2 . CONCLUSION: Vorapaxar is approved for use with @entity4 and/or @entity10 in the secondary prevention of cardiovascular events in stable @entity0 with @entity11 or a history of @entity6 . However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of @entity5 . It is, therefore, essential to balance the need for further reduction of risk of @entity7 event with @entity0 's individual @entity5 risk.

title: Vorapaxar in XXXX Management.

answer: @entity8


abstract: OBJECTIVE: To examine whether biphasic immediate-release (IR)/extended-release (ER) @entity1 ( @entity3 )/ @entity2 ( @entity2 ) 7.5/325-mg tablets have clinically relevant variability in population pharmacokinetics (PK). DESIGN: Post hoc analysis of 2 phase 1 randomized, open-label, multiple-dose crossover studies. SETTING: Single contract research organization clinic. SUBJECTS: @entity0 and @entity0 aged 18 to 55  years with a body mass index of 19 to 30  kg/m(2) and body weight >=   59  kg. METHODS: Fasted @entity0 (N  =  96) received 2 tablets of IR/ER @entity3 / @entity2 7.5/325  mg (total dose, 15/650  mg) every 12  hours for 4.5  days. Population PK analysis was performed using nonlinear mixed effects modeling and evaluated 6 population variables. RESULTS: The average PK estimates for @entity3 were 75  L/hour for clearance (CL/F), 756  L for volume of distribution (V/F), and 0.581  per hour for absorption rate constant (Ka ). Body weight was a statistically significant source of variability in V/F for @entity3 at steady state. Average estimates for @entity2 were 25  L/hour for CL/F and 119  L for V/F. Sex was identified as a statistically significant source of variability in CL/F with predicted values for @entity2 of 25  L/hour in @entity0 and 21  L/hour in @entity0 . Body weight affected variability in V/F, with a predicted value of 193  L in @entity0 and 174  L in @entity0 for a 72-kg @entity0 at steady state. CONCLUSIONS: Dose adjustments of <  50% are not clinically relevant for IR/ER @entity3 / @entity2 7.5/325-mg tablets considering the approved dose of 1 to 2 tablets every 8 to 12  hours; thus, adjustment may be necessary for large deviations from normal body weight but not for sex.

title: Pooled Post Hoc Analysis of Population Pharmacokinetics of @entity1 and XXXX Following Multiple Oral Doses of Biphasic Immediate-Release/Extended-Release @entity1 / @entity2 Tablets.

answer: @entity2


abstract: OBJECTIVE: To examine whether biphasic immediate-release (IR)/extended-release (ER) @entity1 ( @entity3 )/ @entity2 ( @entity2 ) 7.5/325-mg tablets have clinically relevant variability in population pharmacokinetics (PK). DESIGN: Post hoc analysis of 2 phase 1 randomized, open-label, multiple-dose crossover studies. SETTING: Single contract research organization clinic. SUBJECTS: @entity0 and @entity0 aged 18 to 55  years with a body mass index of 19 to 30  kg/m(2) and body weight >=   59  kg. METHODS: Fasted @entity0 (N  =  96) received 2 tablets of IR/ER @entity3 / @entity2 7.5/325  mg (total dose, 15/650  mg) every 12  hours for 4.5  days. Population PK analysis was performed using nonlinear mixed effects modeling and evaluated 6 population variables. RESULTS: The average PK estimates for @entity3 were 75  L/hour for clearance (CL/F), 756  L for volume of distribution (V/F), and 0.581  per hour for absorption rate constant (Ka ). Body weight was a statistically significant source of variability in V/F for @entity3 at steady state. Average estimates for @entity2 were 25  L/hour for CL/F and 119  L for V/F. Sex was identified as a statistically significant source of variability in CL/F with predicted values for @entity2 of 25  L/hour in @entity0 and 21  L/hour in @entity0 . Body weight affected variability in V/F, with a predicted value of 193  L in @entity0 and 174  L in @entity0 for a 72-kg @entity0 at steady state. CONCLUSIONS: Dose adjustments of <  50% are not clinically relevant for IR/ER @entity3 / @entity2 7.5/325-mg tablets considering the approved dose of 1 to 2 tablets every 8 to 12  hours; thus, adjustment may be necessary for large deviations from normal body weight but not for sex.

title: Pooled Post Hoc Analysis of Population Pharmacokinetics of @entity1 and @entity2 Following Multiple Oral Doses of Biphasic Immediate-Release/Extended-Release @entity1 / XXXX Tablets.

answer: @entity2


abstract: OBJECTIVE: To examine whether biphasic immediate-release (IR)/extended-release (ER) @entity1 ( @entity3 )/ @entity2 ( @entity2 ) 7.5/325-mg tablets have clinically relevant variability in population pharmacokinetics (PK). DESIGN: Post hoc analysis of 2 phase 1 randomized, open-label, multiple-dose crossover studies. SETTING: Single contract research organization clinic. SUBJECTS: @entity0 and @entity0 aged 18 to 55  years with a body mass index of 19 to 30  kg/m(2) and body weight >=   59  kg. METHODS: Fasted @entity0 (N  =  96) received 2 tablets of IR/ER @entity3 / @entity2 7.5/325  mg (total dose, 15/650  mg) every 12  hours for 4.5  days. Population PK analysis was performed using nonlinear mixed effects modeling and evaluated 6 population variables. RESULTS: The average PK estimates for @entity3 were 75  L/hour for clearance (CL/F), 756  L for volume of distribution (V/F), and 0.581  per hour for absorption rate constant (Ka ). Body weight was a statistically significant source of variability in V/F for @entity3 at steady state. Average estimates for @entity2 were 25  L/hour for CL/F and 119  L for V/F. Sex was identified as a statistically significant source of variability in CL/F with predicted values for @entity2 of 25  L/hour in @entity0 and 21  L/hour in @entity0 . Body weight affected variability in V/F, with a predicted value of 193  L in @entity0 and 174  L in @entity0 for a 72-kg @entity0 at steady state. CONCLUSIONS: Dose adjustments of <  50% are not clinically relevant for IR/ER @entity3 / @entity2 7.5/325-mg tablets considering the approved dose of 1 to 2 tablets every 8 to 12  hours; thus, adjustment may be necessary for large deviations from normal body weight but not for sex.

title: Pooled Post Hoc Analysis of Population Pharmacokinetics of XXXX and @entity2 Following Multiple Oral Doses of Biphasic Immediate-Release/Extended-Release @entity1 / @entity2 Tablets.

answer: @entity1


abstract: OBJECTIVE: To examine whether biphasic immediate-release (IR)/extended-release (ER) @entity1 ( @entity3 )/ @entity2 ( @entity2 ) 7.5/325-mg tablets have clinically relevant variability in population pharmacokinetics (PK). DESIGN: Post hoc analysis of 2 phase 1 randomized, open-label, multiple-dose crossover studies. SETTING: Single contract research organization clinic. SUBJECTS: @entity0 and @entity0 aged 18 to 55  years with a body mass index of 19 to 30  kg/m(2) and body weight >=   59  kg. METHODS: Fasted @entity0 (N  =  96) received 2 tablets of IR/ER @entity3 / @entity2 7.5/325  mg (total dose, 15/650  mg) every 12  hours for 4.5  days. Population PK analysis was performed using nonlinear mixed effects modeling and evaluated 6 population variables. RESULTS: The average PK estimates for @entity3 were 75  L/hour for clearance (CL/F), 756  L for volume of distribution (V/F), and 0.581  per hour for absorption rate constant (Ka ). Body weight was a statistically significant source of variability in V/F for @entity3 at steady state. Average estimates for @entity2 were 25  L/hour for CL/F and 119  L for V/F. Sex was identified as a statistically significant source of variability in CL/F with predicted values for @entity2 of 25  L/hour in @entity0 and 21  L/hour in @entity0 . Body weight affected variability in V/F, with a predicted value of 193  L in @entity0 and 174  L in @entity0 for a 72-kg @entity0 at steady state. CONCLUSIONS: Dose adjustments of <  50% are not clinically relevant for IR/ER @entity3 / @entity2 7.5/325-mg tablets considering the approved dose of 1 to 2 tablets every 8 to 12  hours; thus, adjustment may be necessary for large deviations from normal body weight but not for sex.

title: Pooled Post Hoc Analysis of Population Pharmacokinetics of @entity1 and @entity2 Following Multiple Oral Doses of Biphasic Immediate-Release/Extended-Release XXXX / @entity2 Tablets.

answer: @entity1


abstract: 1. A purification of @entity3 dehydrogenase is described. 2. The final preparation is active with @entity2 and @entity1 and with a number of @entity4 , but evidence is presented to support the view that a single enzyme is involved. 3. @entity2 showed product inhibition, but at slightly acid pH values there was evidence of co-operative binding. 4. At acid pH values @entity0 was a potent inhibitor and appears to be an allosteric effector. At neutral or alkaline pH values @entity0 behaved as a weak competitive inhibitor. 5. The physiological significance of inhibition by @entity0 is discussed.

title: Purification and properties of XXXX dehydrogenase from potato tubers.

answer: @entity3


abstract: UNASSIGNED: Protein receptor conformations, obtained from @entity0 ( @entity0 ) simulations, have become a promising treatment of its explicit flexibility in molecular docking experiments applied to drug discovery and development. However, incorporating the entire ensemble of @entity0 conformations in docking experiments to screen large candidate compound libraries is currently an unfeasible task. Clustering algorithms have been widely used as a means to reduce such ensembles to a manageable size. Most studies investigate different algorithms using pairwise Root-Mean Square Deviation (RMSD) values for all, or part of the @entity0 conformations. Nevertheless, the RMSD only may not be the most appropriate gauge to cluster conformations when the target receptor has a plastic active site, since they are influenced by changes that occur on other parts of the structure. Hence, we have applied two partitioning methods (k-means and k-medoids) and four agglomerative hierarchical methods (Complete linkage, Ward's, Unweighted Pair Group Method and Weighted Pair Group Method) to analyze and compare the quality of partitions between a data set composed of properties from an enzyme receptor substrate-binding cavity and two data sets created using different RMSD approaches. Ensembles of representative @entity0 conformations were generated by selecting a medoid of each group from all partitions analyzed. We investigated the performance of our new method for evaluating binding conformation of drug candidates to the @entity1 enzyme, which were performed by cross-docking experiments between a 20 ns @entity0 trajectory and 20 different ligands. Statistical analyses showed that the novel ensemble, which is represented by only 0.48% of the @entity0 conformations, was able to reproduce 75% of all dynamic behaviors within the binding cavity for the docking experiments performed. Moreover, this new approach not only outperforms the other two RMSD-clustering solutions, but it also shows to be a promising strategy to distill biologically relevant information from @entity0 trajectories, especially for docking purposes.

title: An Effective Approach for Clustering XXXX Molecular Dynamics Trajectory Using Substrate-Binding Cavity Features.

answer: @entity1


abstract: UNASSIGNED: It is recognised that ageing induces various changes to the @entity0 colonic microbiota. Most relevant is a reduction in bifidobacteria, which is a health-positive genus. Prebiotics, such as galacto-oligosaccharides (GOS), are dietary ingredients that selectively fortify beneficial gut microbial groups. Therefore, they have the potential to reverse the age-related decline in bifidobacteria and modulate associated health parameters. We assessed the effect of GOS mixture (Bimuno (B-GOS)) on gut microbiota, markers of immune function and metabolites in forty elderly (age 65-80 years) volunteers in a randomised, double-blind, placebo (maltodextrin)-controlled, cross-over study. The intervention periods consisted of 10 weeks with daily doses of 5  5  g/d with a 4-week washout period in between. Blood and faecal samples were collected for the analyses of faecal bacterial populations and immune and metabolic biomarkers. B-GOS consumption led to significant increases in bacteroides and bifidobacteria, the latter correlating with increased @entity3 in faecal waters. Higher @entity2 , @entity1 , natural killer cell activity and C-reactive protein and lower @entity4 were also observed. Administration of B-GOS to elderly volunteers may be useful in positively affecting the microbiota and some markers of immune function associated with ageing.

title: Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly XXXX .

answer: @entity0


abstract: BACKGROUND: The objective of this study was to review the available prospective, randomized, controlled trials to determine whether an early ( @entity3 ) or a delayed (DLC) approach to a laparoscopic cholecystectomy is associated with an increase in length of hospitalization after acute @entity2 . METHODS: Medline, the Cochrane Trials Register and EMBASE were searched for prospective, randomized, controlled trials (RCTs) comparing @entity3 versus DLC, published up to May 2014. A meta-analysis was performed using Review Manager 5.0. RESULTS: Nine RCTs were included in a total of 617 who underwent @entity3 and 603 @entity0 who underwent DLC after acute @entity2 . The mean hospital stay was 5.4  days in the @entity3 group and 9.1  days in the DLC group. The meta-analysis showed a mean hospital stay significantly lower in the @entity3 group [ @entity1 ( @entity1 )  =  3.24, 95% confidence interval (CI)  =  1.95-4.54, P  <  0.001]. The major biliary duct injury rate in the @entity3 group was 0.8% (2/247) and 0.9% (2/223) in the DLC group. The meta-analysis showed no significant difference between the @entity3 and DLC groups [relative risk (RR)  =0.96, 95%CI  =  0.25-3.73, P  =  0.950]. CONCLUSION: DLC is associated with a longer total hospital stay but equivalent morbidity as compared to @entity3 for @entity0 presenting with acute @entity2 . @entity3 would appear to be the treatment of choice for @entity0 presenting with @entity3 .

title: Delayed laparoscopic cholecystectomy increases the total hospital stay compared to an early laparoscopic cholecystectomy after acute XXXX : an updated meta-analysis of randomized controlled trials.

answer: @entity2