bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Nonmetastatic Rhabdomyosarcoma in Childhood and Adolescence: Third Study of the International Society of Paediatric Oncology—SIOP Malignant Mesenchymal Tumor 89
Authors: Stevens Michael C.G. , Rey Annie , Bouvet Nathalie , Ellershaw Caroline , Flamant Françoise , Habrand Jean Louis , Marsden H. Basil , Martelli Helene , de Toledo Jose Sanchez , Spicer Richard D , Spooner David , Terrier-Lacombe Marie Jose , van Unnik Adrian , Oberlin Odile 
Published: February 2005

Purpose To improve outcome for children with nonmetastatic rhabdomyosarcoma and to reduce systematic use of local therapy. Patients and Methods Five hundred three previously untreated patients aged from birth to 18 years, recruited between 1989 and 1995, were allocated to one of six treatment schedules by site and stage. Results Five-year overall survival (OS) and event-free survival (EFS) were 71% and 57%, respectively. Primary site, T-stage, and pathologic subtype were independent factors in predicting OS by multivariate analysis. Differences between EFS and OS reflected local treatment strategy and successful re-treatment for some patients after relapse. Patients with genitourinary nonbladder prostate tumors had the most favorable outcome (5-year OS, 94%): the majority were boys with paratesticular tumors treated successfully without alkylating agents. Patients with stage III disease treated with a novel six-drug combination showed improved survival compared with the Malignant Mesenchymal Tumor 84 study (MMT 84; 5-year OS, 60% v 42%, respectively). OS was not significantly better than that achieved in the previous MMT 84 study, but 49% of survivors were cured without significant local therapy. Conclusion Selective avoidance of local therapy is justified in some patients, though further work is required to prospectively identify those for whom this is most applicable. Exclusion of alkylating agents is justified for the most favorable subset of patients. The value of the new six-drug chemotherapy combination is being evaluated further in a randomized study (MMT 95).
Phase I Study of BMS-214662, a Farnesyl Transferase Inhibitor in Patients With Acute Leukemias and High-Risk Myelodysplastic Syndromes
Authors: Cortes Jorge , Faderl Stefan , Estey Elihu , Kurzrock Razelle , Thomas Deborah , Beran Miloslav , Garcia-Manero Guillermo , Ferrajoli Alessandra , Giles Francis , Koller Charles , O'Brien Susan , Wright John , Bai Stephen A. , Kantarjian Hagop 
Published: February 2005

Purpose To investigate the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of BMS-214662, a farnesyl transferase (FTase) inhibitor, in patients with acute leukemias and high-risk myelodysplastic syndromes (MDS). Patients and Methods Patients with relapsed or refractory acute leukemias or MDS, or previously untreated but poor candidates for chemotherapy, were included in this phase I study with a 3 + 3 dose escalation design. BMS-214662 was administered as a 1-hour bolus once weekly at doses of 42 to 157 mg/m2. Once the MTD was identified, the schedule was changed to a 24-hour continuous infusion once weekly (starting dose, 300 mg/m2). Results Thirty patients were treated at a dose of 42 (n = 1), 56 (n = 3), 84 (n = 3), 118 (n = 13), 157 (n = 6) or 300 mg/m2 (n = 4). DLT occurred in 3 patients at 157 mg/m2, including nausea, vomiting, diarrhea, hypokalemia and cardiovascular problems. No DLT occurred with 24-hour continuous infusion. MTD with a 1-hour infusion was 118 mg/m2, with no MTD identified with the 24-hour infusion. Plasma concentrations of BMS-214662 correlated with the dose. Inhibition of FTase activity of approximately 60% occurred after the infusion with recovery to near baseline after 24 hours. Five patients had evidence of antileukemia activity, including two with complete remission with incomplete platelet recovery, one with hematologic improvement, and two with morphologic leukemia-free state. Conclusion BMS-214662 is well tolerated at doses of up to 118 mg/m2 as a 1-hour infusion. The toxicity profile and efficacy may be improved with prolonged exposure. Further investigation of this agent in leukemia is warranted.
Late Referrals to Specialized Palliative Care Service in Japan
Authors: Morita Tatsuya , Akechi Tatsuo , Ikenaga Masayuki , Kizawa Yoshiyuki , Kohara Hiroyuki , Mukaiyama Taketo , Nakaho Toshimichi , Nakashima Nobuaki , Shima Yasuo , Matsubara Tatsuhiro , Uchitomi Yosuke 
Published: February 2005

PurposeTo clarify the bereaved family's perceptions about the appropriateness of timing when physicians first referred patients to palliative care units, and to identify the factors contributing to family-perceived late referrals.Subjects and MethodsA multicenter questionnaire survey was conducted on 630 bereaved family members of cancer patents who were admitted to palliative care units in Japan. A total of 318 responses were analyzed (effective response rate, 62%).ResultsHalf of the bereaved family members regarded the timing of referrals to palliative care units as late or very late, while less than 5% of families reported early referrals (very late [19%, n = 59], late [30%, n = 96], appropriate [48%, n = 151], early [1.6%, n = 5], and very early [2.2%, n = 7]). Multiple regression analyses revealed that the independent determinants of family-perceived late referrals were: family belief before admission that palliative care shortens the patient's life, insufficient in-advance discussion about preferred end-of-life care between patients/families and physicians, families' insufficient preparation for changes of patient conditions, and hospital admission before referrals.ConclusionIn Japan, the timing of referrals to palliative care units was late or very late from the families' perspectives. The independent determinants of family-perceived late referrals were: family misconception about palliative care, inadequate communication with physicians, and families' insufficient preparation for deterioration of patients' conditions. Systematic strategies to overcome these barriers would contribute to providing appropriate palliative care at all stages of cancer.
A Library Synthesis of Pyrazoles by Azomethine Imine Cycloaddition to the Polymer-supported Vinylsulfone
Authors: Fuchi Nobuhiro , Doi Takayuki , Takahashi Takashi 
Published: February 2005

Abstract
1,3-Dipolar cycloaddition of azomethine imines to the polymer-supported vinylsulfone was achieved. Pyrazole derivatives bearing various aryl groups were synthesized regioselectively.
Controlling Chemoselectivity in Reactions of Unprotected Naphthalene-1-carboxylic Acid with Strong Bases
Authors: Tilly David , Castanet Anne-Sophie , Mortier Jacques 
Published: February 2005

Abstract
Whereas treatment of unprotected naphthalene-1-carboxylic acid with alkyllithiums (RLi) affords 1,4-addition products, the reaction with LTMP/Me3SiCl under in situ quench conditions provides the arylsilane arising out from the substitution of lithium 2-lithionaphthalene carboxylate with Me3SiCl. With the Lochmann–Schlosser superbase (n-BuLi/t-BuOK), metalation occurs preferentially in the position adjacent to CO2Li although the peri and ortho, peri-dilithiated species are also formed.
Respiratory Rhythm Entrainment by Somatic Afferent Stimulation
Authors: Potts Jeffrey T. , Rybak Ilya A. , Paton Julian F. R. 
Published: February 2005

Respiratory and locomotor patterns are coupled during locomotion. The objectives of this study were to (1) demonstrate that respiratory rhythms are entrained by sensory input from somatic afferents, (2) establish whether the parabrachial nucleus mediates entrainment, (3) examine responses of single respiratory neurons in the ventral respiratory group (VRG) to somatic afferent stimulation, and (4) use a computational model of the pontomedullary respiratory network (Rybak et al., 2004a,b) to suggest neuronal mechanisms for entrainment.We used anin situpreparation in young rats that retained pontomedullary respiratory circuits and spinal pathways transmitting somatosensory input. We demonstrate that rhythmic stimulation of somatic afferents entrains respiratory rhythm on a 1:1 basis (1:1), increasing breathing frequency up to ∼1.4-2.2 times greater than spontaneous frequency. Stable entrainment occurred only when stimuli were delivered during expiration. Reversible blockade of the lateral parabrachial nucleus eliminated entrainment. Somatic afferent stimulation produced significant increases in the firing rate of augmenting expiratory (E2) neurons but shortened the firing duration of postinspiratory (post-I) neurons. A computational model reproduced 1:1 entrainment and other experimental findings based on the assumption that the somatic afferents initiate early onset of inspiration via activation of medullary E2 neurons. The model also predicted that afferent stimulation evoked transient hyperpolarization of ramp-inspiratory (ramp-I) neurons. This was confirmed experimentally by intracellular recording from ramp-I neurons. Our experimental and modeling results demonstrate that an entrainment pathway from somatic afferents to the VRG via the lateral parabrachial nucleus causes resetting of respiratory rhythm through excitation of E2 and consequent inhibition of post-I neurons.
Galantamine Activates Muscle-Type Nicotinic Acetylcholine Receptors without Binding to the Acetylcholine-Binding Site
Authors: Akk Gustav , Steinbach Joe Henry 
Published: February 2005

Galantamine (Reminyl; Janssen Pharmaceutica, Titusville, NJ) belongs to a class of acetylcholinesterase inhibitors approved for symptomatic treatment of Alzheimer's disease. The drug presumably acts by raising and prolonging the profile of acetylcholine (ACh) via an inhibitory effect on the esterase. However, there is also evidence demonstrating that galantamine can activate the nicotinic ACh receptor or modulate its activation by ACh.In this study, we have examined the ability of galantamine to directly activate the muscle-type nicotinic ACh receptor or to modulate receptor activation by selected nicotinic agonists.Studies of direct activation by galantamine demonstrated that this ligand is a low-efficacy agonist of the muscle-type ACh receptor. Point mutations in the M2-M3 linker (αS269I) and the M2 transmembrane domain (ϵT264P) had similar effects on receptor activation by galantamine and nicotinic agonists, suggesting that the general features of receptor activation by galantamine are similar to that in the presence of ACh.Experiments performed in the simultaneous presence of galantamine and various nicotinic ligands showed that channel activation by the nicotinic ligands studied (ACh, carbachol, and choline) was not affected by the presence of galantamine at concentrations up to 100 μm. In addition, galantamine did not reduce the initial rate of binding for125I-α-bungarotoxin. These results demonstrate that galantamine does not interfere with the occupation of the nicotinic agonist binding site by ACh, carbachol, or choline. We conclude that galantamine activates the muscle-type ACh receptor by interacting with a binding site that is distinct from the site for nicotinic agonists.
Levels of Cytokine Receptor Activator of Nuclear Factor κB Ligand in Gingival Crevicular Fluid in Untreated Chronic Periodontitis Patients
Authors: Vernal Rolando , Chaparro Alejandra , Graumann Rebecca , Puente Javier , Valenzuela Maria Antonieta , Gamonal Jorge 
Published: February 2005

Background: Receptor activator of nuclear factor κB ligand (RANK‐L) is a cytokine involved in the regulation of osteoclastogenesis in bone remodeling and inflammatory osteolysis. One of the major causes of tooth loss in humans is bone destruction. The aim of our study was to determine the presence of RANK‐L in gingival crevicular fluid (GCF) samples from adult patients with untreated chronic periodontitis and in healthy controls. We also identified the RANK‐L present in lesions undergoing episodic attachment loss from GCF.Methods: GCF samples were collected from two periodontally affected sites (probing depth ≥5 mm, attachment loss ≥3 mm) in 20 patients (N = 40). After monitoring for 4 months, seven patients showed active periodontal disease, and GCF samples were collected from one active and one inactive site (N = 14 samples). The comparison with healthy controls was carried out by collecting GCF samples from 12 healthy volunteers (N = 24 samples). GCF was collected using a paper strip, and enzymelinked immunosorbent assay (ELISA) was performed to determine the total amount of RANK‐L.Results: RANK‐L was found in a higher proportion (85%) of samples from patients than from controls (46%). The total amount of RANK‐L was significantly higher in patients (115.53 ± 78.18 picograms [pg]) than in healthy subjects (63.08 ± 55.08 pg) (P = 0.003). Active sites, presumably associated with tissue destruction, had significantly higher levels of RANK‐L than their inactive counterparts (125.95 pg versus 91.80 pg, P = 0.007).Conclusion: GCF total amount of RANK‐L is significantly increased in periodontal disease, supporting its role in the alveolar bone loss developed in this disease. J Periodontol 2004;75: 1586‐1591.
Augmented Transforming Growth Factor‐β1 in Gingival Crevicular Fluid of Smokers With Chronic Periodontitis
Authors: Stein Sidney H. , Green Bryan E. , Scarbecz Mark 
Published: February 2005

Background: Patients who smoke are at increased risk for chronic periodontitis (CP). Also, CP patients who smoke exhibit significantly less reduction of probing depths and gains in clinical attachment compared to non‐smokers following periodontal therapy. Several studies suggest that the effects of smoking on the host response may be paramount in regulating the basal systemic inflammatory status and therapeutic outcomes in this cohort. Growth factors, specifically transforming growth factor β1 (TGF‐β1), are critical in regulating the wound healing response by controlling cell division, differentiation, and motility. The hypothesis to be tested was that gingival crevicular fluid (GCF) TGF‐β1 production was altered in smokers compared to nonsmokers with CP.Methods: GCF was collected from smokers and non‐smokers with CP, both at baseline and 1 to 2 weeks after initial therapy. GCF volume was determined using an electronic device and TGF‐β1 concentration was measured by enzyme‐linked immunosorbent assay (ELISA).Results: Smokers exhibited a higher mean concentration of GCF TGF‐β1 at baseline compared to non‐smokers (P = 0.03). After initial therapy, smokers exhibited significantly less reduction in mean GCF volume compared to non‐smokers (P = 0.04).Conclusions: Augmented constitutive production of GCF TGF‐β1 in smokers may explain the clinical appearance of fibrotic gingival tissue exhibited by this patient cohort. A diminished reduction in GCF volume in smokers following root instrumentation suggests a chronic inflammatory status in conjunction with an ineffective host response. These findings support the concept that smokers with CP display an altered local inflammatory response after initial therapy, perhaps symptomatic of colonization by residual periodontal pathogens.J Periodontol 2004;75:1619‐1626.
Association Analysis Between Interleukin‐1 Family Polymorphisms and Generalized Aggressive Periodontitis in a Chinese Population
Authors: Li Qi Yan , Zhao Hong Shan , Meng Huan Xin , Zhang Li , Xu Li , Chen Zhi Bin , Shi Dong , Feng Xiang Hui , Zhu Xiao Ling 
Published: February 2005

Background: It has been suggested that aggressive periodontitis (AgP) has a genetic basis, but this theory has not been confirmed. The intent of this investigation was to study whether specific interleukin (IL)‐1 genotypes and/or alleles could be used to predict susceptibility to generalized AgP (GAgP) in Chinese.Methods: The GAgP group consisted of 122 patients, and the control group included 95 healthy subjects. Single nucleotide polymorphisms at IL‐1A (+4845) and IL‐1B (–511, +3954) were analyzed by standard polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assay. The polymorphism of a variable number tandem repeat (VNTR) in intron 2 of IL‐1RN was detected by PCR amplification and fragment size analysis.Results: There was no significant association of IL‐1 polymorphisms with GAgP in the unstratified subjects. However, when cases were stratified by gender, the frequencies of A2+ genotype and allele 2 at IL‐1A +4845 were significantly increased in male patients compared to male controls (genotype: odds ratio [OR] 5.58, 95% confidence interval [CI]: 1.09 to 28.68, P = 0.039; allele: OR 4.97, 95% CI: 1.01 to 24.50, P = 0.049; adjusted for age and smoking status). The frequency of IL‐1B –511 A1/A2 heterozygote was significantly increased in male GAgP group compared to male controls (adjusted OR 3.16, 95% CI: 1.01 to 9.89, P = 0.048). In females, no significant differences were found between patients and controls in corresponding analyses at all polymorphic loci. A possible combined effect of IL‐1B –511 polymorphism and smoking on the elevated risk to GAgP was observed. The OR of GAgP for combined A2+ genotype and smoking was 12.45 (95% CI: 1.43 to 108.06, P = 0.022), and for combined allele 2 and smoking was 18.25 (95% CI: 2.32 to 143.86, P = 0.006).Conclusions: The polymorphisms of IL‐1A +4845 and IL‐1B –511 may play an important role in determining GAgP susceptibility in Chinese males. Furthermore, a possible combined effect of the polymorphism of IL‐1B –511 and smoking on GAgP susceptibility was suggested. J Periodontol 2004;75:1627‐1635.
Distribution of Systemic Ciprofloxacin and Doxycycline to Gingiva and Gingival Crevicular Fluid
Authors: Lavda Maria , Clausnitzer C. Esther , Walters John D. 
Published: February 2005

Background: Systemic fluoroquinolones and tetracyclines reach steady‐state levels in gingival crevicular fluid (GCF) that are several‐fold higher than their levels in serum. The mechanism by which this occurs is unclear, but gingival fibroblasts are known to accumulate these agents. Uptake by fibroblasts could enhance their distribution to gingiva. To test this hypothesis, steady‐state levels of these agents were assayed in serum, gingival connective tissue (GCT), and GCF.Methods: Healthy subjects who needed resective periodontal surgery participated in the study. Approximately 78 hours prior to the surgical appointment, each subject began a 3‐day regimen of ciprofloxacin or doxycycline. At the surgical appointment (scheduled approximately 6 hours after the last dose), samples of blood and GCT were collected. GCF samples were collected on paper strips and measured with an electronic device. Samples were extracted and analyzed by high performance liquid chromatography.Results: Mean ciprofloxacin levels in serum, GCT, and GCF were 0.40 µg/ml, 1.38 µg/g, and 1.66 µg/ml, respectively (P <0.001, N = 9). For doxycycline, these levels were 1.11 µg/ml, 2.03 µg/g, and 2.41 µg/ml, respectively (P = 0.002, N = 8). For both agents, the GCT and GCF levels were significantly higher than serum levels (P <0.05), but not significantly different from each other.Conclusions: Our findings suggest that fibroblasts could play an important role in the distribution of fluoroquinolones and tetracyclines to the gingiva. By accumulating these agents in GCT, fibroblasts could contribute to the relatively high levels they attain in GCF. J Periodontol 2004;75:1663‐1667.
Periodontal Repair in Dogs: Analysis of Histometric Assessments in the Supraalveolar Periodontal Defect Model
Authors: Koo Ki‐Tae , Polimeni Giuseppe , Albandar Jasim M. , Wikesjö Ulf M.E. 
Published: February 2005

Background: Traditionally, the mean value from histometric assessments of several histologic sections from the same site has been, used for the histometric characterization of the site. The histometric analysis of the supraalveolar periodontal defect model uses observations from buccal and lingual sites in three stepserial sections representing the central aspect of the mesial and distal root for the third and fourth mandibular premolar teeth. The objectives of this study were to investigate the correlations and determine whether there are significant differences in the measurement values of various histometric parameters between the three step‐serial sections and to test the hypothesis that, in this animal model, histometric assessments using the most central section of each root are comparable to the mathematical means of corresponding assessments of the site using the three step‐serial sections.Methods: Histometric analysis using light microscopy, an attached digital camera system, and a personal computer‐based image analysis system including a custom program for the supraalveolar periodontal defect model was performed on histologic sections acquired from one jaw quadrant in each of 12 dogs. The animals had received a protocol including placement of a coral biomaterial and guided tissue regeneration (GTR) membranes, and were evaluated following a 4‐week healing interval. Twelve parameters were assessed using three central step‐serial sections from each root. For each parameter, pair‐wise comparisons were performed using the mixed models analysis of variance, and the correlations between measurements were assessed by the intraclass correlation coefficient (ICC).Results: For all parameters assessed, there were no significant differences (P >0.05) among the three sections. The differences between the central section and the means of the three step‐serial sections were small and not statistically significant. Parameters that could be assessed on most or all specimens, such as defect height and area, membrane height, and bone regeneration area, showed high correlations among the three step‐serial sections (intraclass coefficient [ICC] ∼ 0.91 to 0.98), and between each of the three sections and the mean for the three step‐serial sections (ICC ≥0.95). The most central section had somewhat higher correlation with the mean than measurements made on the lateral sections.Conclusion: The results suggest that using the supraalveolar periodontal defect model representative histometric data can be obtained evaluating only the central section from each defect site. J Periodontol 2004;75:1688‐1693.
In Vitro Biocompatibility of a New Titanium‐29Niobium‐13Tantalum‐4.6Zirconium Alloy With Osteoblast‐Like MG63 Cells
Authors: Naganawa T. , Ishihara Y. , Iwata T. , Koide M. , Ohguchi M. , Ohguchi Y. , Murase Y. , Kamei H. , Sato N. , Mizuno M. , Noguchi T. 
Published: February 2005

Background: Titanium‐29niobium‐13tantalum‐4.6zirconium (TiNb) has recently been developed as a new implant material. TiNb is composed of non‐toxic elements and has a lower modulus of elasticity than the other titanium alloys. However, its biocompatibility has not been adequately characterized. The aim of this study was to evaluate the biocompatibility of TiNb using an osteoblast‐titanium co‐culture system.Methods: MG63 cells were cultured on three kinds of titanium disks: TiNb, pure titanium (pTi), and titanium‐6aluminum‐4vanadium (TiAl), prepared with two different surfaces, a polished and acid‐etched surface and a machined‐grooved surface. The surface topography and roughness were evaluated by scanning electron microscopy (SEM). After 48 hours culture, the number of proliferating cells and prostaglandin E2 (PGE2) production in the culture supernatant were determined.Results: There was no significant difference in surface roughness among the three titanium disks with a polished and acidetched surface. After 48 hours of culture, the number of cells was significantly reduced on pTi and TiAl compared to TiNb and the control. PGE2 production was significantly higher on pTi than on TiAl, TiNb, and the control. We further examined the effect of surface roughness on PGE2 production using machine‐grooved titanium disks. While pTi and TiAl stimulated the production of PGE2 depending on surface roughness, roughened TiNb did not affect PGE2 production.Conclusions: These results suggest that TiNb may exhibit favorable biocompatibility because it has an efficient surface topography for cell proliferation, and the level of PGE2 production does not depend on surface roughness. We conclude that TiNb may be useful as an implant material. J Periodontol 2004;75: 1701‐1707.