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971.
Hillier TA Stone KL Bauer DC Rizzo JH Pedula KL Cauley JA Ensrud KE Hochberg MC Cummings SR 《Archives of internal medicine》2007,167(2):155-160
BACKGROUND: Whether repeat bone mineral density (BMD) measurement adds benefit beyond the initial BMD measurement in predicting fractures in older women is unknown. METHODS: We prospectively measured total hip BMD in 4124 older women (mean +/- SD age, 72 +/- 4 years) from 1989 to 1990 and again 8 years later. Incident nontraumatic hip and nonspine fractures were validated by radiology reports (>95% follow-up). In addition, spine fractures were defined morphometrically in 2129 of these women by lateral spine x-ray films from 1991 to 1992 and then again 11.4 years later. Prediction of fracture risk was assessed with proportional hazards models and receiver operating characteristic curves for BMD measures. RESULTS: Over a mean of 5 years after the repeat BMD measure, 877 women experienced an incident nontraumatic nonspine fracture (275 hip fractures). In addition, 340 women developed a spine fracture. After adjustment for age and weight change, initial and repeat BMD measurements were similarly associated with fracture risk (per unit standard deviation lower in BMD) for nonspine (hazard ratio, 1.6), spine (odds ratio, 1.8-1.9), and hip (hazard ratio, 2.0-2.2) fractures (P<.001 for all models). Areas under the receiver operating characteristic curves (AUC) revealed no significant differences to discriminate nonspine (AUC, 0.65), spine (AUC, 0.67-0.68), or hip (AUC, 0.73-0.74) fractures between models with initial BMD, repeat BMD, or initial BMD plus change in BMD. Stratification by initial BMD t scores (normal, osteopenic, or osteoporotic), high bone loss, or hormone therapy did not alter results. CONCLUSION: In healthy, older, postmenopausal women, repeating a measurement of BMD up to 8 years later provides little additional value besides the initial BMD measurement for predicting incident fractures. 相似文献
972.
Decreased sleep in heart failure: are medications to blame? 总被引:1,自引:0,他引:1
Scheer FA Stone PH Shea SA 《Archives of internal medicine》2007,167(10):1098-9; author reply 1099-100
973.
End points to establish the efficacy of new agents in the treatment of acute leukemia 总被引:2,自引:0,他引:2 下载免费PDF全文
Appelbaum FR Rosenblum D Arceci RJ Carroll WL Breitfeld PP Forman SJ Larson RA Lee SJ Murphy SB O'Brien S Radich J Scher NS Smith FO Stone RM Tallman MS 《Blood》2007,109(5):1810-1816
Federal regulations provide 2 pathways for approval of new agents for the treatment of acute leukemia, regular and accelerated approval. Regular approval requires evidence of clinical benefit, which is generally defined as either prolongation of life or improved quality of life, or an effect on an end point established as a surrogate for clinical benefit. Accelerated approval can be obtained based on demonstration of an effect on a surrogate measure "reasonably likely" to predict clinical benefit, but requires demonstration of clinical benefit after approval as well. The acute leukemias are a heterogeneous and relatively uncommon group of diseases. The design and execution of prospective randomized clinical trials demonstrating prolongation of life or improved quality of life for patients with these disorders can be difficult and costly and require lengthy follow-up. Thus, the development of novel trial design and inclusion of validated surrogate markers for clinical benefit are needed. To explore some of the issues pertinent to the choice of end points for drug approval in acute leukemia, the Food and Drug Administration invited the American Society of Hematology to participate in the organization and conduct of a joint workshop. In this report, we present the results of that effort. 相似文献
974.
Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy 总被引:15,自引:2,他引:13
975.
Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning 总被引:1,自引:0,他引:1 下载免费PDF全文
Graves SS Hogan W Kuhr CS Diaconescu R Harkey MA Georges GE Sale GE Zellmer E Baran SW Baran S Jochum C Stone B Storb R 《Blood》2007,110(1):418-423
Although hematopoietic cell transplantation (HCT) is generally accomplished using a single donor, multiple donors have been used to enhance the speed of engraftment, particularly in the case of umbilical cord blood grafts. Here we posed the question in the canine HCT model whether stable dual-donor chimerism could be established using 2 DLA-identical donors. We identified 8 DLA-identical littermate triplets in which the marrow recipients received 2 Gy total body irradiation followed by marrow infusions from 2 donors and postgrafting immunosuppression. All 8 dogs showed initial "trichimerism," which was sustained in 5 dogs, while 2 dogs rejected one of the allografts and remained mixed chimeras, and 1 dog rejected both allografts. Immune function in one trichimeric dog, as tested by mixed leukocyte culture response and antibody response to sheep red blood cells, was found to be normal. Five dogs received kidney grafts from one of their respective marrow donors at least 6 months after HCT without immunosuppressive drugs, and grafts in 4 dogs are surviving without rejection. In summary, following nonmyeloablative conditioning, simultaneous administration of marrow grafts from 2 DLA-identical littermates could result in sustained trichimerism, and immunologic tolerance could include a kidney graft from one of the marrow donors. 相似文献
976.
Correlation between dietary intake and occurrence of prostate cancer has gained significant support in recent years. Although a direct correlation has yet to be proven between inflammation and prostate cancer, chronic or recurrent inflammation has been hypothesized to be the major predisposing factor for this disease. The authors have been studying Zyflamend, a novel herbal anti-inflammatory mixture, as a potential chemopreventive agent in a phase 1 trial for patients diagnosed with prostatic intraepithelial neoplasia. They report the results of the first patient who has completed the 18-month study in which 24 patients were assigned to a cohort and placed on successive herbal supplement regimen starting with Zyflamend alone. 相似文献
977.
BACKGROUND: Understanding anti-non-gal antibody response is of significance for success in xenotransplantation. Long-term anti-non-gal response in humans was studied in patients transplanted with porcine patellar tendon (PT) lacking alpha-gal epitopes, for replacing ruptured anterior cruciate ligament (ACL). METHODS: Porcine PTs were treated with recombinant alpha-galactosidase to eliminate alpha-gal epitopes and with glutaraldehyde for moderate cross-linking of collagen fibers. The processed pig PTs were implanted to replace ruptured ACL in patients. RESULTS: In five of six evaluable subjects, the xenografts have continued to function for over two years and passed all functional stability assessments. Thus, processed porcine PT seems to be appropriate for replacing ruptured human ACL. Enzyme-linked immunosorbent assay and Western blot studies indicated that all subjects produced anti-non-gal antibodies against multiple pig xenoproteins, but not against human ligament proteins. Production of anti-non-gal antibodies peaked two to six months posttransplantation and disappeared after two years. CONCLUSIONS: These antibodies contribute to a low-level inflammatory process that aids in gradual xenograft replacement by infiltrating host fibroblasts that align with the pig collagen "scaffold" and secrete collagen matrix. The assays monitoring anti-non-gal antibodies will help to determine whether long-term survival of live organ xenografts requires complete suppression of this antibody response. 相似文献
978.
PURPOSE: We describe biopsy results in patients with prostate cancer treated with brachytherapy. MATERIALS AND METHODS: A total of 1,562 men with localized prostate cancer were treated with permanent prostate brachytherapy, of whom 508 agreed to ultrasound guided biopsies 2 years after the completion of all therapy. Median followup was 6.7 years (range 2 to 14.6) and median prostate specific antigen was 7.4 ng/ml (range 0.3 to 300). Disease was categorized as Gleason score less than 7 in 74.8% of patients, stage T2a or less in 64.2%, low risk in 43.1%, intermediate risk in 24.2% and high risk in 32.7%. Of the 508 men 315 (62%) received (125)I, 110 (21.7%) received (103)Pd and 83 (16.3%) received (103)Pd and external beam radiotherapy. A total of 237 men (46.7%) received a short course of hormonal therapy (3 to 9 months). Subsequent biopsies were performed after 2 years if initial biopsy was positive or prostate specific antigen increased. Post-implantation dosimetry results were grouped into low, normal and high dose. Associations were tested by chi-square analysis. Survival functions were calculated with Kaplan-Meier analysis and Cox regression. RESULTS: A total of 643 biopsies were performed in 508 men between 2 and 11 years after implantation. Of the 508 men 39 (7.7%) had a final positive biopsy. Positive biopsy was associated with high prostate specific antigen (p=0.035), stage (p=0.003), risk (p=0.024), no hormonal therapy (p=0.002) and low dose (p<0.0001). On multivariate analysis only dose and hormonal therapy were significant (p<0.0001 and p=0.004, respectively). Of the patients 80% were free of PSA failure at 10 years if final biopsy was negative compared to 27.3% with a positive biopsy (p<0.0001). Death from prostate cancer was associated with a positive biopsy (OR 18.5, 95% CI 2.3-143, p<0.0001). Of the 52 men with a positive biopsy at year 2, 23 (44.2%) had negative results on subsequent biopsy, while 10 of the 456 (2.2%) with negative 2-year biopsies showed positive results. Positive biopsy occurred in the prostate only in 31 of 39 men (79.5%), in the prostate and seminal vesicles in 3 (7.7%), and in the seminal vesicles only in 5 (12.8%). CONCLUSIONS: Patients undergoing prostate brachytherapy must receive an adequate radiation dose to eradicate local disease. Hormonal therapy may benefit local control in patients with intermediate to high risk disease. Extraprostatic biopsies should be performed in patients with local failure who are considering salvage therapy to rule out seminal vesicle involvement. 相似文献
979.
980.
PURPOSE: To examine associations of potentially aetiological significance for the development of pseudoseizures by comparing patients with recent onset pseudoseizures with patients with recent onset epilepsy. METHODS: A prospective study of consecutive patients with recent onset pseudoseizures and epilepsy presenting to two Swedish hospitals. Demographic characteristics, somatic symptoms, depression severity, personality disorder, potential childhood aetiological factors and recent life events were elicited from clinical data and a research interview, which included a structured clinical interview for DSM-IV, a measure of perceived parental care and a life events inventory. RESULTS: Twenty patients with pseudoseizures of duration less than 12 months (mean 5.4 months) were compared with 20 patients with recent onset epilepsy. There was no statistically significant difference in the rate of current psychiatric disorder. Patients with recent onset pseudoseizures were however more likely to have a borderline personality disorder (P<0.05), and to recollect less parental warmth and more paternal rejection (P=0.0001) in childhood. They had no more life events in the 3 months prior to onset but did report more when the whole year before onset was assessed (P<0.001). CONCLUSIONS: Perceived childhood neglect, borderline personality, and an excess of life events over the preceding year is associated with pseudoseizures of recent onset more than with epilepsy. The study was limited by the small sample size making type two errors likely. However, by selecting both cases and controls with recent onset symptoms, the potential bias of differing illness durations and complicating factors of chronicity that have affected previous studies was avoided. 相似文献