bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Thrombospondin-1–Mimetic Angiogenesis Inhibitor ABT-510 in Patients With Advanced Cancer
Authors: Hoekstra Ronald , de Vos Filip Y.F.L. , Eskens Ferry A.L.M. , Gietema Jourik A. , van der Gaast Ate , Groen Harry J.M. , Knight Raymond A. , Carr Robert A. , Humerickhouse Rod A. , Verweij Jaap , de Vries Elisabeth G.E. 
Published: July 2005

Purpose ABT-510 is an angiogenesis inhibitor derived from thrombospondin-1, a naturally occurring inhibitor of angiogenesis. We investigated ABT-510, which was administered subcutaneously in patients with advanced solid malignancies, to assess safety, pharmacokinetics, and serum markers of angiogenesis. Patients and Methods ABT-510 was administered subcutaneously as a continuous infusion (100 mg/24 h) and bolus injections (100, 200, and 260 mg once daily; 50 and 100 mg twice daily) in 28-day cycles. Results Thirty-nine patients received a total of 144 treatment cycles. Administration by continuous infusion was hampered by the onset of painful skin infiltrates at the injection site. In the bolus injection regimens, the most common toxicities observed were mild injection-site reactions and fatigue. Maximum-tolerated dose was not defined, but 260 mg was defined as the maximum clinically practical dose. ABT-510 pharmacokinetics were linear across the dosage ranges tested, and the potential therapeutic threshold (plasma concentrations > 100 ng/mL > 3 h/d) was achieved with all dose regimens. Median serum basic fibroblast growth factor (bFGF) levels decreased from 14.1 pg/mL (range, 0.5 to 77.7 pg/mL) at baseline to 3.2 pg/mL (range, 0.2 to 29.4 pg/mL) after 56 days of treatment (P = .003). No correlations with time on study or ABT-510 dose or exposure were observed for individual changes in bFGF. Stable disease lasting for six cycles or more was seen in six patients. Conclusion ABT-510 demonstrated a favorable toxicity profile and linear and time-independent pharmacokinetics with biologically relevant plasma concentrations. The significant number of patients with prolonged stable disease and the convenient method of dosing merit further studies with this angiogenesis inhibitor.
Cognitive and Adaptive Outcome in Low-Grade Pediatric Cerebellar Astrocytomas: Evidence of Diminished Cognitive and Adaptive Functioning in National Collaborative Research Studies (CCG 9891/POG 9130)
Authors: Beebe Dean W. , Ris M. Douglas , Armstrong F. Daniel , Fontanesi John , Mulhern Raymond , Holmes Emi , Wisoff Jeffrey H. 
Published: July 2005

Purpose Clinicians often assume that children with posterior fossa tumors are at minimal risk for cognitive or adaptive deficits if they do not undergo cranial irradiation. However, small case series have called that assumption into question, and have also suggested that nonirradiated cerebellar tumors can cause location-specific cognitive and adaptive impairment. This study (1) assessed whether resected but not irradiated pediatric cerebellar tumors are associated with cognitive and adaptive functioning deficits, and (2) examined the effect of tumor location and medical complications on cognitive and adaptive functioning. Patients and Methods The sample was composed of 103 children aged 3 to 18 years with low-grade cerebellar astrocytomas, who underwent only surgical treatment as part of Children's Cancer Group protocol 9891 or Pediatric Oncology Group protocol 9130. The sample was divided into three groups based on primary tumor location: vermis, left hemisphere, or right hemisphere. Data were collected prospectively on intelligence, academic achievement, adaptive skills, behavioral functioning, and pre-, peri-, and postsurgical medical complications. Results The sample as a whole displayed an elevated risk for cognitive and adaptive impairment that was not associated consistently with medical complications. Within this group of children with cerebellar tumors, tumor location had little effect on cognitive, adaptive, or medical outcome. Conclusion We did not replicate previous findings of location-specific effects on cognitive or adaptive outcome. However, the elevated risk of deficits in this population runs contrary to clinical lore, and suggests that clinicians should attend to the functional outcomes of children who undergo only surgical treatment for cerebellar tumors.
Fertility- and Menopause-Related Information Needs of Younger Women With a Diagnosis of Early Breast Cancer
Authors: Thewes B. , Meiser B. , Taylor A. , Phillips K.A. , Pendlebury S. , Capp A. , Dalley D. , Goldstein D. , Baber R. , Friedlander M.L. 
Published: July 2005

PurposeThe use of chemotherapy and endocrine therapies in the treatment of premenopausal women carries with it reproductive and gynecologic implications that young women may find distressing and discordant with plans for childbearing. This multicenter study aimed to investigate fertility- and menopause-related information needs among young women with a diagnosis of early-stage breast cancer.Patients and MethodsTwo hundred twenty-eight women with a diagnosis of early-stage breast cancer who were aged 40 years or younger at diagnosis and who were 6 to 60 months after diagnosis were entered onto the trial. Participants completed a mailed self-report questionnaire that included a purposely designed fertility- and menopause-related information needs survey and standardized measures of distress, anxiety, quality of life, menopausal symptoms, and information-seeking style.ResultsSeventy-one percent of participants discussed fertility-related issues with a health professional as part of their breast cancer treatment, and 86% discussed menopause-related issues. Consultation with a fertility or menopause specialist was the most preferred method of obtaining this information. Receiving fertility-related information was rated as being significantly more important than receiving menopause-related information at time of diagnosis (P < .001) and at treatment decision making (P = .058). Receiving menopause-related information was rated as being significantly more important than receiving fertility-related information during adjuvant treatment (P < .05), at completion of adjuvant treatment (P < .001), and during follow-up (P < .001). Common questions, sources of information, and correlates of perceived importance were identified.ConclusionThe results of this study suggest that younger women have unmet needs for fertility- and menopause-related information and provide preliminary empirical data to guide the development of better fertility- and menopause-related patient education materials for younger women with a diagnosis of early breast cancer.
Identifying Patients at Risk for Significant Versus Clinically Insignificant Postoperative Prostate-Specific Antigen Failure
Authors: D'Amico Anthony V. , Chen Ming-Hui , Roehl Kimberly A. , Catalona William J. 
Published: July 2005

Purpose We evaluated whether men at risk for significant versus clinically insignificant prostate-specific antigen (PSA) failure after radical prostatectomy could be identified using information available at diagnosis. Patients and Methods A prospective prostate cancer screening study that enrolled, diagnosed, and treated 1,011 men with radical prostatectomy at Barnes-Jewish Hospital (St Louis, MO) from January 1, 1989, to June 1, 2002, for localized prostate cancer formed the study cohort. Preoperative predictors of a postoperative PSA doubling time (DT) of less than 3 months and more than 12 months or no PSA failure were identified using logistic regression. Results A preoperative PSA velocity more than 2.0 ng/mL/yr (P = .001) and biopsy Gleason score 7 (P = .006) or 8 to 10 (P = .003) were significantly associated with having a postoperative PSA DT less than 3 months. A PSA level less than 10 ng/mL (P = .005), a nonpalpable cancer (P = .001) with a Gleason score ≤ 6 (P = .0002), and a preoperative PSA increase that did not exceed 0.5 ng/mL/yr (P = .03) were significantly associated with a postoperative PSA DT of at least 12 months or no PSA failure. Most men with these preoperative characteristics and a postoperative PSA DT of 12 months or more had a persistent postoperative PSA level of at least 0.2 ng/mL that did not exceed 0.25 ng/mL after a median follow-up of 3.6 years. Conclusion A postoperative PSA DT less than 3 months is associated with a preoperative PSA velocity more than 2.0 ng/mL/yr and high-grade disease. Select men with a postoperative PSA DT more than 12 months may not require salvage radiation therapy.
Randomized Trial Comparing Cyclophosphamide, Epirubicin, and Fluorouracil With Cyclophosphamide, Methotrexate, and Fluorouracil in Premenopausal Women With Node-Positive Breast Cancer: Update of National Cancer Institute of Canada Clinical Trials Group Trial MA5
Authors: Levine Mark N. , Pritchard Kathleen I. , Bramwell Vivien H.C. , Shepherd Lois E. , Tu Dongsheng , Paul Nancy 
Published: July 2005

Purpose Certain anthracycline-containing adjuvant chemotherapy regimens are associated with improved relapse-free survival (RFS) and overall survival (OS) compared with the classic regimen of cyclophosphamide, methotrexate, and fluorouracil in women with early-stage breast cancer. Patients and Methods Between 1989 and 1993, 710 pre- and perimenopausal women with axillary node–positive breast cancer were randomly assigned to either cyclophosphamide 75 mg/m2 orally days 1 through 14, epirubicin 60 mg/m2 intravenously days 1 and 8, and fluorouracil 500 mg/m2 intravenously days 1 and 8 (CEF) or CMF (cyclophosphamide 100 mg/m2 orally days 1 through 14, methotrexate 40 mg/m2 intravenously days 1 and 8, and fluorouracil 600 mg/m2 intravenously days 1 and 8). On the basis of follow-up to May 1997 (median follow-up time, 59 months), there was a statistically significant improvement in RFS and OS for CEF compared with CMF. Results The trial results are now updated, with a median follow-up of 10 years for live patients. The 10-year RFS is 52% for patients who received CEF compared with 45% for CMF patients (hazard ratio [HR] for CMF v CEF = 1.31; stratified log-rank, P = .007). The 10-year OS for patients who received CEF and CMF are 62% and 58%, respectively (HR for CMF v CEF = 1.18; stratified log-rank, P = .085). The rates of acute leukemia have not changed since the original report, whereas the rates of congestive heart failure are slightly higher but acceptable (four patients [1.1%] in the CEF group v one patient [0.3%] in the CMF group). Conclusion The previously demonstrated benefit of CEF compared with CMF adjuvant chemotherapy is maintained with longer follow-up in the MA5 trial.
Use of the Internet to Obtain Cancer Information Among Cancer Patients at an Urban County Hospital
Authors: Helft Paul R. , Eckles Rachael E. , Johnson-Calley Cynthia Stair , Daugherty Christopher K. 
Published: July 2005

Purpose To evaluate rates, predictors, and barriers to use of the Internet to obtain cancer information among a cohort of cancer patients at an urban county hospital. Patients and Methods Of 208 cancer patients approached, 200 patients completed a structured interview study examining Internet use, perceptions of the accuracy of Internet information, and barriers to use. Results Only 10% of participants reported using the Internet themselves to obtain cancer information. Another 21% reported exposure to Internet information through proxies. The most common barrier to Internet use cited was lack of Internet access, with 44% reporting that they would use the Internet to obtain cancer information if they had Internet access. Younger age and more years of formal education were significantly associated with Internet use, although race and income were not. Less education, African American race, and female sex were associated with lower estimates of the accuracy of Internet information. Fewer years of formal education was associated with increased likelihood of reporting confusion after reading Internet information. Conclusion Very few cancer patients in this study of a cohort of generally disadvantaged individuals used the Internet themselves to obtain cancer information, although many more desired to do so. Significant opportunities for Web-based interventions aimed at improving cancer care outcomes in this population of cancer patients exist. However, further study will be needed to determine how to make such intervention accessible, trustworthy, and understandable to the disadvantaged.
Inelastic Background and Peak Area Determination in X-Ray Photoelectron Spectroscopy (ESCA)
Authors: Proctor Andrew , Hercules David M. 
Published: July 2005

Analysis of the Au 4f ESCA spectra of thin gold films deposited over a graphite base shows that as the separation from the main photoelectron peak, ΔE, increases the background decreases. Conversely, the effect of a contaminant overlayer on solid gold gives rise to a background which increases as ΔE increases. There is, therefore, a considerable variety of background profiles which can be encountered in real samples, which depends markedly on the element, its concentration, and its distribution in the sample. Over the region of the photoelectron line signal itself, the simple integral description which assumes that the background is proportional to the number of electrons of higher kinetic energy is reasonably valid and is suggested for peak area measurement when a nonlinear profile is needed. Direct integration and curve fitting techniques constitute the two main methods of peak area measurement. Simulated Ni 2p spectra are used to compare the effectiveness of the simple integral and linear background profiles for producing the correct peak areas. Although the simple integral profile shows more consistency and is to be preferred in general, certain fortuitous cancellation effects, particularly with non-monochromatized spectra, make areas using the linear background fairly accurate in some instances. Curve fitting can overcome many of the problems of direct integration resulting from severe peak overlap. Two types of Gaussian/Lorentzian functions with a suitable exponential tailing function, which has a finite area over reasonable integration limits, are discussed with regard to their use in non-linear least-squares curve fitting methods. Also discussed is the usefulness of composite and difference spectra as simpler methods of determining the relative areas of overlapping peaks.
Selectively Excited Luminescence in GaAs
Authors: Bohn P. W. , Harris T. D. , Bhat R. , Cox H. M. 
Published: July 2005

Relaxation of donor and acceptor bound excitons, (D°, X) and (A°, X), to a final state in which the impurity atoms are left in an internally excited state has been used in several laboratories as a tool in assigning the chemical identity of the impurity species. In many specific samples, however, this excited final state emission is obscured by the free to bound (e−, A°) or an interfering donor to acceptor (D°, A°) transition. Enhanced emission from excited final state relaxation processes in GaAs has been observed using selective excitation to increase the population of the appropriate initial states. Increases in emission intensity of approximately 8 for (D°, X)* and 30 for (A°, X)* were observed. The excitation wavelength dependence of the enhancement is explained in terms of instrumental parameters and free exciton absorption. The converse of the selective excitation experiment was performed in order to learn more about the mechanisms which populate the levels giving rise to the analytically interesting emission. Anti-Stokes emission was observed in the near-gap region in high purity GaAs for the first time. The emission intensity as a function of excitation wavelength data is discussed in terms of a simple parallel pathway model for upconversion. The model postulates two parallel mechanisms which may populate the emitting states, and the access to one or the other of the two is determined by the energy of the incident photon. The model explains both the absolute intensity behavior of the (D°, X) and (D+, X) emission and the intensity ratio trend as a function of excitation wavelength.
Magnetic resonance imaging study in older fragile X premutation male carriers
Authors: Loesch Danuta Z. , Litewka Lucas , Brotchie Peter , Huggins Richard M. , Tassone Flora , Cook Mark 
Published: July 2005

AbstractSome carriers of a “premutation” allele of the FMR1 gene develop late‐onset tremor/ataxia. We conducted a magnetic resonance imaging volumetric study in an unselected sample of eight older male premutation carriers. Volumetric measures, including total brain volume, and the volumes of cerebrum, cerebellum, and cerebral cortex all were significantly reduced in premutation carriers compared with similar data from 21 age‐matched normal controls. Total brain and cerebral volumes were significantly related to the number of CGG repeats in the FMR1 gene. Moreover, increased hippocampal volume indicates this premutation may account for both neurodegenerative and neurodevelopmental changes. Ann Neurol 2005;58:326–330
Chromosome 1p loss: A favorable prognostic factor in low‐grade gliomas
Authors: Kujas Michèle , Lejeune Julie , Benouaich‐Amiel Alexandra , Crinière Emmanuelle , Laigle‐Donadey Florence , Marie Yannick , Mokhtari Karima , Polivka Marc , Bernier Michèle , Chretien Fabrice , Couvelard Anne , Capelle Laurent , Duffau Hugues , Cornu Philippe , Broët Philippe , Thillet Joëlle , Carpentier Antoine F. , Sanson Marc , Hoang‐Xuan Khê , Delattre Jean‐Yves 
Published: July 2005

AbstractSearch for loss of heterozygosity on chromosomes 1p, 9p, 10q, and 19q, epidermal growth factor receptor (EGFR) gene amplification, and p53 expression was performed in a series of 131 low‐grade gliomas. The profile of molecular changes, clinical findings, and histology were subsequently correlated with the course of the disease, mainly progression‐free survival. When these parameters were considered as candidate variables in a multivariate analysis, only loss of heterozygosity on chromosome 1p was associated with increased progression‐free survival (hazard ratio, 0.521), indicating a major favorable prognostic role of this genetic alteration in low‐grade gliomas. Ann Neurol 2005;58:322–326
Xenon and hypothermia combine to provide neuroprotection from neonatal asphyxia
Authors: Ma Daqing , Hossain Mahmuda , Chow Andre , Arshad Mubarik , Battson Renee M. , Sanders Robert D. , Mehmet Huseyin , Edwards A. David , Franks Nicholas P. , Maze Mervyn 
Published: July 2005

AbstractPerinatal asphyxia can result in neuronal injury with long‐term neurological and behavioral consequences. Although hypothermia may provide some modest benefit, the intervention itself can produce adverse consequences. We have investigated whether xenon, an antagonist of the N‐methyl‐D‐aspartate subtype of the glutamate receptor, can enhance the neuroprotection provided by mild hypothermia. Cultured neurons injured by oxygen‐glucose deprivation were protected by combinations of interventions of xenon and hypothermia that, when administered alone, were not efficacious. A combination of xenon and hypothermia administered 4 hours after hypoxic‐ischemic injury in neonatal rats provided synergistic neuroprotection assessed by morphological criteria, by hemispheric weight, and by functional neurological studies up to 30 days after the injury. The protective mechanism of the combination, in both in vitro and in vivo models, involved an antiapoptotic action. If applied to humans, these data suggest that low (subanesthetic) concentrations of xenon in combination with mild hypothermia may provide a safe and effective therapy for perinatal asphyxia. Ann Neurol 2005;58:182–193
Trophic factor distribution predicts functional recovery in parkinsonian monkeys
Authors: Gash Don M. , Zhang Zhiming , Ai Yi , Grondin Richard , Coffey Robert , Gerhardt Greg A. 
Published: July 2005

AbstractGlial cell line–derived neurotrophic factor (GDNF) promotes the survival, growth, and regeneration of dopamine neurons in the midbrain that degenerate in Parkinson's disease. However, translating successful animal studies into effective clinical therapy for Parkinson's disease has proved difficult. In this article, using pulsed infusion for convection‐enhanced delivery of GDNF, we have analyzed two variables hypothesized to be important for achieving efficacy: dose and GDNF distribution in the target tissue. Motor functions were significantly improved in rhesus monkeys with unilateral 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine–induced parkinsonism that received midbrain infusion of GDNF for 10 weeks. The volume of distribution of GDNF in the five trophic factor recipients varied more than fivefold, from 59 to 325 mm3, and significantly correlated with motor function improvements. Significant increases were evident in the number of midbrain dopamine neurons immunopositive for tyrosine hydroxylase in both the substantia nigra and ventral tegmental area. Based on neurochemical and quantitative morphological measures, GDNF administration promoted recovery of both the nigrostriatal and ventral tegmental area–nucleus accumbens dopaminergic pathways without producing evident side effects. Increasing the dose threefold did not increase efficacy, suggesting that after achieving a critical threshold, GDNF tissue distribution is more important than dose for trophic stimulation of dopamine neurons. Ann Neurol 2005;58:224–233
Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: Dihydrolipoamide acetyltransferase (E2) deficiency
Authors: Head Rosemary A. , Brown Ruth M. , Zolkipli Zarazuela , Shahdadpuri Raveen , King Mary D. , Clayton Peter T. , Brown Garry K. 
Published: July 2005

AbstractPyruvate dehydrogenase deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. Most cases are caused by mutations in the X‐linked gene for the E1α subunit of the complex. Mutations in DLAT, the gene encoding dihydrolipoamide acetyltransferase, the E2 core component of the complex, have not been described previously. We report two unrelated patients with pyruvate dehydrogenase deficiency caused by defects in the E2 subunit. Both patients are less severely affected than typical patients with E1α mutations and both have survived well into childhood. Episodic dystonia was the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent. The patients had neuroradiological evidence of discrete lesions restricted to the globus pallidus, and both are homozygous for different mutations in the DLAT gene. The clinical presentation and neuroradiological findings are not typical of pyruvate dehydrogenase deficiency and extend the clinical and mutational spectrum of this condition. Ann Neurol 2005;58:234–241