bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enrollment of Elderly Patients in Clinical Trials for Cancer Drug Registration: A 7-Year Experience by the US Food and Drug Administration
Authors: Talarico Lilia , Chen Gang , Pazdur Richard 
Published: November 2004

Purpose To analyze the age-related enrollment of cancer patients onto registration trials of new drugs or new indications approved by the US Food and Drug Administration from 1995 to 2002. Patients and Methods This study involved retrospective analyses of demographic data of cancer patients enrolled onto registration trials. The data on 28,766 cancer patients from 55 registration trials were analyzed according to age distributions of ≥ 65, ≥ 70, and ≥ 75 years. The rates of enrollment in each age group for each cancer were compared with the corresponding rates in the US cancer population. The age distributions of the US cancer population were derived from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the period 1995 to 1999 based on the 2000 US Census. Results The proportions of the overall patient populations aged ≥ 65, ≥ 70, and ≥ 75 years were 36%, 20%, and 9% compared with 60%, 46%, and 31%, respectively, in the US cancer population. Statistically significant under-representation of the elderly (P < .001) was noted in registration trials for all cancer treatment except for breast cancer hormonal therapies. Patients aged ≥ 70 years accounted for most of the under-representation. Conclusion Elderly were under-represented in the registration trials of new cancer therapies. Various strategies may be needed to evaluate cancer therapies for the elderly in prospective clinical trials and to improve cancer care in the elderly population.
An experimental study of acoustically enhanced NAPL dissolution in porous media
Authors: Vogler Eric T. , Chrysikopoulos Constantinos V. 
Published: November 2004

AbstractThe effects of acoustic waves on the dissolution of dense nonaqueous phase liquids in water saturated porous media are investigated. Experiments of trichloroethylene (TCE) ganglia dissolution within a water saturated column, packed with glass beads, are conducted. Acoustic waves with pressure amplitudes ranging from 0 to 1625 Pa and frequencies ranging from 0 to 285 Hz are employed to the interstitial fluid at the inlet of the packed column. Effluent dissolved TCE concentrations are observed to increase up to 120% in the presence of acoustic pressure waves compared to the case where TCE dissolution without acoustic waves is monitored. The observed effluent dissolved TCE concentration increase is attributed to enhanced mass flux at the TCE‐water interface, caused by acoustic waves. Highest dissolution rates occur at discrete frequencies suggesting resonance effects or the presence of standing waves. Although acoustic waves enhance TCE dissolution, they dissipate almost exponentially with distance from the acoustic source. © 2004 American Institute of Chemical Engineers AIChE J, 50: 3271–3280, 2004
Swelling and erosion affecting flavor release from glassy particles in water
Authors: Bouquerand P. E. , Maio S. , Normand V. , Singleton S. , Atkins D. 
Published: November 2004

AbstractA model of flavor release from encapsulated flavor particles immersed in water has been developed that correlates well with experimental data. Flavor release from particles was determined by measuring both the quantities released from the particle to water and from water to air in the headspace. The model presented here predicts a very different release with time from the encapsulated flavor if the particle develops a hydrogel at the surface (swelling) compared to gradual erosion. Controlled heating showed more retention of flavor when the particle swells compared to a more rapid flavor release under conditions of particle erosion. © 2004 American Institute of Chemical Engineers AIChE J, 50: 3257–3270, 2004
Three new families with arterial tortuosity syndrome
Authors: Wessels Marja W. , Catsman‐Berrevoets Coriene E. , Mancini Grazia M.S. , Breuning Martijn H. , Hoogeboom Jeanette J.M. , Stroink Hans , Frohn‐Mulder Ingrid , Coucke Paul J. , Paepe Anne De , Niermeijer Martinus F. , Willems Patrick J. 
Published: November 2004

AbstractArterial tortuosity syndrome (ATS) is a rare condition with autosomal recessive inheritance characterized by connective tissue abnormalities. The most specific clinical findings are cardiovascular anomalies including tortuosity, lengthening, aneurysm, and stenosis formation of major arteries. Also ventricular hypertrophy is frequently present. Other anomalies are skin hyperextensibility and cutis laxa, joint laxity or contractures of the joints, and inguinal herniae. Histology shows disruption of elastic fibers of the media. These features suggest that ATS is a connective tissue disorder. A biochemical or molecular defect has not yet been identified. We describe here nine additional ATS patients from three consanguineous Moroccan families and review a total of 35 patients with this uncommon condition. © 2004 Wiley‐Liss, Inc.
Autoimmune disorders in Kabuki syndrome
Authors: Ming Jeffrey E. , Russell Karen L. , McDonald‐McGinn Donna M. , Zackai Elaine H. 
Published: November 2004

AbstractKabuki syndrome is associated with abnormalities in multiple organ systems. While many of the anomalies are congenital malformations, other clinical manifestations may not appear until later in childhood. Among these associated conditions, autoimmune abnormalities have been described in several patients. These include idiopathic thrombocytopenic purpura (ITP), hemolytic anemia, thyroiditis, and vitiligo. In this report, we describe five affected patients with autoimmune manifestations. Four patients had ITP, and two of these patients had concurrent hemolytic anemia. The fifth patient had vitiligo. Two of the patients with ITP had a chronic and relapsing course. Of note, some of these patients also had hypogammaglobulinemia. The autoimmune disorders may be manifestations of abnormal immune regulation. We conclude that Kabuki syndrome is associated with an increased incidence of autoimmune disorders. In addition, the presence of an underlying immune defect may predispose these children to a chronic course of these autoimmune conditions. © 2004 Wiley‐Liss, Inc.
Intellectual abilities and adaptive behavior of children and adolescents with Kabuki syndrome: A preliminary study
Authors: Mervis Carolyn B. , Becerra Angela M. , Rowe Melissa L. , Hersh Joseph H. , Morris Colleen A. 
Published: November 2004

AbstractVery little is known about the intellectual abilities and adaptive behavior of individuals who have Kabuki syndrome, beyond the fact that most individuals with this syndrome have mental retardation. To fill this gap, we have completed psychological assessments of 11 children and adolescents with Kabuki syndrome. Results indicated that most of the participants functioned in the range of mild mental retardation, with both intellectual and adaptive behavior in the mildly deficient range and problem behaviors, if any, limited to mild difficulties with inattention and/or hyperactivity–impulsivity and mild problems with obsession/anxiety. At the lower extreme, one child evidenced severe mental retardation and profound adaptive behavior impairment accompanied by serious externalizing and internalizing problem behaviors. At the upper extreme, one adolescent had average intelligence and adaptive behavior, with problem behaviors well within the normal range for his chronological age. Most participants evidenced relative intellectual strengths in verbal and reasoning abilities and a relative weakness in visuospatial construction abilities. This pattern affected adaptive behavior as well, yielding a relative strength in Social Interaction and Communicative Skills and considerable weakness in Motor Skills and Personal Living Skills. © 2004 Wiley‐Liss, Inc.
Developmental outcome in Kabuki syndrome
Authors: Vaux Keith K. , Jones Kenneth L. , Jones Marilyn C. , Schelley Susan , Hudgins Louanne 
Published: November 2004

AbstractOver the last 20 years, a wide spectrum of congenital anomalies have been described in association with Kabuki syndrome (KS). However, very little information is available on developmental outcome. As more individuals with this syndrome are recognized and reported, it appears that as many as one‐sixth may have normal intelligence. The purpose of this report is to describe the developmental outcome in 15 patients with KS, to determine whether a recognizable pattern of disabilities exist, and whether developmental outcome correlates with the presence of malformations. We ascertained 15 patients with KS from three dysmorphology and clinical genetics services in which developmental milestones and formal developmental testing were available. Based on these patients and a review of the literature, in the absence of major structural brain anomalies, the average intelligence quotient (IQ) in patients with this condition fall within the mild mental retardation range, however, specific developmental outcomes are widely variable, ranging from severe MR to normal intelligence. The presence or absence of hearing loss or major malformations, other than those involving the brain, was not predictive of developmental outcome. Published 2004 Wiley‐Liss, Inc.
Genotype–phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B)
Authors: Panagiotakaki Eleni , Tzetis Maria , Manolaki Nina , Loudianos Giorgos , Papatheodorou Athanasios , Manesis Emmanuel , Nousia‐Arvanitakis Sanda , V Syriopoulou , Kanavakis Emmanuel 
Published: November 2004

AbstractWilson disease (WND) is caused by mutations in the ATP7B gene and exhibits substantial allelic heterogeneity. In this study we report the results of molecular analyses of 20 WND families not described previously. When combined with our prior results, the cohort includes 93 index patients from 69 unrelated families. Twenty different mutations accounted for 86% of the WND chromosomes. The most frequent were p.H1069Q (35%), p.R969Q (12%), c.2530delA (7%), p.L936X (7%), p.Q289X (7%), and p.I1148T (3%). We also present here a detailed phenotypic assessment for patients whose molecular result was previously reported. Thirty cases were homozygous for 9 different mutations, 13 of which were homozygous for p.H1069Q, and 7 for p.R969Q. Mutations p.H1069Q and p.R969Q appeared to confer a milder disease as patients showed disease onset at a later age, and were associated with milder severity when found in trans with severe mutations. Predicted nonsense and frameshift mutations were associated with severe phenotypic expression with earlier disease onset and lower ceruloplasmin values. WND can be treated by copper‐chelation therapy, particularly if the disease is diagnosed before irreversible tissue damage occurs. Our results on the effect of predicted nonsense and frameshift mutations are especially important for early medical intervention in presymptomatic infants and children with these genotypes. © 2004 Wiley‐Liss, Inc.
Craniofacial structure in Marfan syndrome: A cephalometric study
Authors: De Coster Peter , Pauw Guy De , Martens Luc , De Paepe Anne 
Published: November 2004

AbstractMarfan syndrome (MFS) is a connective tissue disorder with autosomal dominant inheritance. Mutations in the FBN1 gene cause deficient processing of fibrillin‐1, the main constituent of extracellular microfibrils, affecting tissues displaying elastic properties. Clinical manifestations are widespread and involve the skeletal, ocular, cardiovascular and pulmonary systems, skin and integumentum, and dura. A highly arched palate and retrognathia have been assigned to the symptoms with minor diagnostic specificity, although epidemiological data on prevalence are lacking yet. Twenty‐six patients with MFS (n = 26) were studied for craniofacial characteristics using cephalometric measurements on lateral cranial radiographs. The purposes of this study were (1) to compare cephalometric variables of MFS group with age‐ and sex‐matched population norms, and (2) to assess differences in palatal vault dimensions among adult MFS (n = 17) and matched controls (n = 32) by means of cephalometric measurements. Significant differences with population norms were found in the structures of the cranial base, the maxillary complex, the mandible body, and the relations of the jaws with respect to the cranial base and to each other. Palatal height and palatal length were significantly larger in MFS, and were significantly correlated to each other and to the height of the maxillo‐alveolar processus. The present data disprove in part previously reported findings, possibly due to biased patient selection in these studies or demographic differences. However, a strong correlation was found between maxillary/mandibular retrognathia, long face, highly arched palate, and MFS. A combination of both intrinsic genetic factors and environmental factors is suggested as a possible explanation for specific morphogenetic aspects of the craniofacial complex in MFS. © 2004 Wiley‐Liss, Inc.
NSAIDs increase survival in the Sandhoff disease mouse: Synergy with N‐butyldeoxynojirimycin
Authors: Jeyakumar Mylvaganam , Smith David A. , Williams Ian M. , Borja Mario Cortina , Neville David C. A. , Butters Terry D. , Dwek Raymond A. , Platt Frances M. 
Published: November 2004

AbstractThe GM2 gangliosidoses are caused by incomplete catabolism of GM2 ganglioside in the lysosome, leading to progressive storage and a neurodegenerative clinical course. An inflammatory response (microglial activation, macrophage infiltration, oxidative damage) has been found to be a consequence of GM2 storage in the brain, although it remains unclear whether this contributes to pathogenesis or disease progression. In this study, we treated Sandhoff disease mice with nonsteroidal antiinflammatory drugs (indomethacin, aspirin, and ibuprofen) and antioxidants (L‐ascorbic acid and α‐tochopherol acetate). The treated mice lived significantly longer than untreated littermates (12–23%, p < 0.0001) and showed a slower rate of disease progression (p < 0.001). When aspirin treatment was combined with substrate reduction therapy, synergy resulted (11%, p < 0.05) with a maximum improvement of 73% in survival (p < 0.00001). This study demonstrates that inflammation contributes to disease progression and identifies antiinflammatory and antioxidant therapies as a potential adjunctive approach to slow the clinical course of this and related disorders. Ann Neurol 2004;56:642–649
Improvement in the mechanical properties of poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) by preorientation
Authors: Hassan Mohamed K. , Abdel‐Latif Samir A. , El‐Roudi Omar M. , Sharaf Mohamed A. , Noda Isao , Mark James E. 
Published: November 2004

AbstractPreoriented poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (Nodax™) films were obtained via the drawing of films to prestretching ratios ranging from 200 to 1000%. As expected, preorientation resulted in substantial improvements in the mechanical properties of the films from the corresponding increases in the amount and nature of the crystallinity present. Stress–strain curves in elongation showed a yield peak, which was relatively broad for the unoriented samples but became sharper, with a well‐defined neck, as the extent of preorientation was increased. In addition, the preoriented films had higher modulus, toughness, yield stress, and tensile strength values. The attribution of these changes in the mechanical properties to changes in the crystallinity was supported by X‐ray diffraction measurements. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2257–2262, 2004
Characteristics of poly(vinyl pyrrolidone)/poly(acrylic acid) interpolymer complex prepared by template polymerization of acrylic acid: Effect of reaction solvent and molecular weight of template
Authors: Chun Myung‐Kwan , Cho Chong‐Su , Choi Hoo‐Kyun 
Published: November 2004

AbstractPoly(vinyl pyrrolidone) (PVP)/poly(acrylic acid) (PAA) interpolymer complexes were prepared, in ethanol or dimethylformamide (DMF), by template polymerization of acrylic acid in the presence of PVP (MW: 42.5 or 1100 K) used as the template. FTIR analysis showed that the complexes were formed through hydrogen bonding between the carboxyl groups of the PAA and the carbonyl groups of the PVP. The glass‐transition temperature (Tg) of the complex, prepared in ethanol, was higher than that of the component polymers, whereas the Tg of the complex, prepared in DMF, was located between that of the component polymers. The dissolution rate of the complex was affected by the molecular weight of the PVP and the reaction solvent. The release rate of ketoprofen from the complexes showed a pH dependency, and was slower at a lower pH. The ketoprofen release rate from the complex was controlled mainly by the dissolution rate of the complex above the pKa of PAA (4.75) and by the diffusion rate below the pKa. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2390–2394, 2004
Novel mucoadhesive polymer: Synthesis and mucoadhesion of poly[acrylic acid‐co‐poly(ethylene glycol) monomethylether monomethacrylate‐co‐dimethylaminoethyl methacrylate]
Authors: Xiang Jun , Li Xiaoling 
Published: November 2004

AbstractThis study was to design a mucoadhesive based on the biological and physicochemical properties of the buccal mucosa to achieve optimal mucoadhesion in the aqueous buccal environment. Since the buccal surface is negatively charged, a series of novel mucoadhesive poly[acrylic acid‐co‐poly(ethylene glycol) monomethylether monomethacrylate‐co‐dimethylaminoethyl methacrylate] [poly (AA‐PEGMM‐DMEMA)] were synthesized by incorporating the cationic monomer DMEMA into poly(AA‐PEGMM) to enhance the interactions between the mucohadhesive polymer and the buccal mucosa. The compositions of poly(AA‐PEGMM‐DMEMA) were varied by changing the content of DMEMA from 0 to 4.8 mol % while keeping the mole ratio of AA to PEGMM at a constant 9 : 1. It was found that the force of mucoadhesion of poly(AA‐PEGMM‐DMEMA) increased initially, as DMEMA content increased, and reached the maximum at 1% of DMEMA. Further increasing the content of DMEMA decreased the mucoadhesion. The polymers with 0.5 to 2.9% DMEMA appeared to have maximum mucoadhesion after prehydration for 5 min. An ATR–FTIR spectroscopy study revealed that intrapolymer interactions and intersurface interactions played opposite roles in the mucoadhesion performance of the polymers. Optimal mucoadhesion can be achieved by balancing these two interactions. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94:2431–2437, 2004
On the potential of organoclay with respect to conventional fillers (carbon black, silica) for epoxidized natural rubber compatibilized natural rubber vulcanizates
Authors: Teh P. L. , Mohd Ishak Z. A. , Hashim A. S. , Karger‐Kocsis J. , Ishiaku U. S. 
Published: November 2004

AbstractOnium modified montmorillonite (organoclay) was compounded with natural rubber (NR) in an internal mixer and cured by using a conventional sulfuric system. Epoxidized natural rubber with 50 mol % epoxidation (ENR 50) in 10 parts per hundred rubber (phr) was used as a compatibilizer in this study. For comparison purposes, two commercial fillers: carbon black (grade N330) and silica (grade vulcasil‐S) were used. Cure characteristics were carried out on a Monsanto MDR2000 Rheometer. Organoclay filled vulcanizate showed the lowest values of torque maximum, torque minimum, scorch, and cure times. The kinetics of cure reaction showed organoclay could behave as a cocuring agent. The mechanical testing of the vulcanizates involved the determination of tensile and tear properties. The improvement of tensile strength, elongation at break, and tear properties in organoclay filled vulcanizate were significantly higher compared to silica and carbon black filled vulcanizates. In terms of reinforcing efficiency (RE), organoclay exhibited the highest stiffness followed by silica and carbon black filled vulcanizates. Scanning electron microscopy revealed that incorporation of various types of fillers has transformed the failure mechanism of the resulting NR vulcanizates compared to the gum vulcanizates. Dynamic mechanical thermal analysis (DMTA) revealed that the stiffness and molecular relaxation of NR vulcanizates are strongly affected by the filler–rubber interactions. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2438–2445, 2004
Electrorheological behaviors of barium titanate/gelatin composite hydrogel elastomers
Authors: Gao Lingxiang , Zhao Xiaopeng 
Published: November 2004

AbstractElectrorheological (ER) elastomers, based on a gelatin hydrogel as matrix in which barium titanate ER particles are dispersed, were investigated. The behavior of particles was observed by a microscopic method. The ER effects of the elastomers are described with the compression modulus as a function of both particle concentration and intensity of the externally applied electric field. The result demonstrates that the particles were aligned in the matrix under an externally applied dc electric field. Furthermore, it was found that alignment of the particles increases the elastomer's modulus. In addition, both the chain effect and filler effect of the particles can dominate the modulus. The peak of modulus appears when using the elastomer with a particle weight fraction of 1.5% because of the complex dominations of the two effects. In like manner, the largest incremental modulus appears. Based on the results, we found that the modulus of the elastomer cured under an electric field is greater than that without an electric field, and increases with the increasing field. Thus ER behavior of the elastomer can be controlled by the electric field intensity. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2517–2521, 2004
Identification and detection of the periostin gene in cardiac development
Authors: Norris Russell A. , Kern Christine B. , Wessels Andy , Moralez E. Iris , Markwald Roger R. , Mjaatvedt Corey H. 
Published: November 2004

AbstractPeriostin, a member of the fasciclin gene family, acts as a cell adhesion molecule through binding to cell surface integrins. Periostin expression has previously been shown to increase substantially following transforming growth factor β (TGF‐β) and bone morphogenetic protein stimulation. As these molecules are indispensable for cardiac development, we sought to clone the chicken ortholog of periostin and evaluate its spatiotemporal expression pattern during heart morphogenesis. We show by Northern analysis, whole mount and section in situ hybridization experiments that periostin is predominantly expressed in the developing endothelium of the ventricular trabeculae as well as in the endothelium and mesenchyme of the outflow tract and atrioventricular endocardial cushions. Cardiac expression continues into fetal development where periostin is seen predominantly in the valve leaflets and supporting chordae tendinae. © 2004 Wiley‐Liss, Inc.
Synthesis of Dimeric Trifluoromethoxyacridine‐derived Pathogen‐inactivating Nucleic Acid Intercalators
Authors: Csuk René , Raschke Christian , Göthe Gunnar , Reißmann Stefan 
Published: November 2004

AbstractA series of antiviral active compounds consisting of an intercalating acridine‐derived part, a spacer region and a reactive EDTA‐derived conjugate was synthesized in an easy sequence. Thus, suitably mono‐protected 1, ω‐alkyldiamines gave, upon reaction with 9‐chloro‐2‐trifluoromethoxyacridine, followed by deprotection and reaction with EDTA dianhydride, the target molecules. Incorporation of their Fe(II) complexes in the presence of ascorbate gave a reduction of the phage titer of MS2 phages by several logarithmic decades.