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51.
Elizabeth S Hart Marilyn H Kelly Beth Brillante Clara C Chen Navid Ziran Janice S Lee Penelope Feuillan Arabella I Leet Harvey Kushner Pamela G Robey Michael T Collins 《Journal of bone and mineral research》2007,22(9):1468-1474
Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy. INTRODUCTION: Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder in which normal bone is replaced by abnormal fibro-osseous tissue. Variable amounts of skeletal involvement and disability occur. The age at which lesions are established, the pace at which the disease progresses, if (or when) the disease plateaus, and how these parameters relate to the onset of disability are unknown. To answer these questions, we performed a retrospective analysis of a group of subjects with FD. MATERIALS AND METHODS: One hundred nine subjects with a spectrum of FD were studied for up to 32 years. Disease progression was assessed in serial (99)Tc-MDP bone scans by determining the location and extent of FD lesions using a validated bone scan scoring tool. Physical function and the need for ambulatory aids were assessed. RESULTS: Ninety percent of the total body disease skeletal burden was established by age 15. Disease was established in a region-specific pattern; in the craniofacial region, 90% of the lesions were present by 3.4 yr, in the extremities, 90% were present by 13.7 yr, and in the axial skeleton, 90% were present by 15.5 yr. Twenty-five of 103 subjects eventually needed ambulatory aids. The median age at which assistance was needed was 7 yr (range, 1-43 yr). The median bone scan score for subjects needing assistance was 64.3 (range, 18.6-75) compared with 23.1 (range, 0.5-63.5) in the unassisted subjects (p < 0.0001). Among subjects needing assistance with ambulation, 92% showed this need by 17 yr. CONCLUSIONS: The majority of skeletal lesions and the associated functional disability occur within the first decade of life. The implication is that the window of time for preventative therapies is narrow. Likewise, therapeutic interventions must be tailored to where the patient is in the natural history of the disease (i.e., progressive disease [young] versus established disease [older subjects]). These findings have implications for prognosis, the timing and type of therapy, and the development of trials of new therapies and their interpretation. 相似文献
52.
Scott L Kominsky Michele Doucet Kelly Brady Kristy L Weber 《Journal of bone and mineral research》2007,22(1):37-44
Bone metastases develop in approximately 30% of patients with RCC, and the mechanisms responsible for this phenomenon are unknown. We found that TGF-beta1 stimulation of RCC bone metastasis cells promotes tumor growth and bone destruction possibly by stimulating paracrine interactions between tumor cells and the bone. INTRODUCTION: Bone metastasis is a frequent complication and causes marked morbidity in patients with renal cell carcinoma (RCC). Surprisingly, the specific mechanisms of RCC interaction with bone have been scarcely studied despite the inability to prevent or effectively treat bone metastasis. Bone is a reservoir for various growth factors including the pleiotropic cytokine TGF-beta1. TGF-beta1 has been shown to have tumor-supportive effects on advanced cancers and evidence suggests its involvement in promoting the development of breast cancer bone metastasis. Here, we studied the potential role of TGF-beta1 in the growth of RCC bone metastasis (RBM). MATERIALS AND METHODS: To inhibit TGF-beta1 signaling, RBM cells stably expressing a dominant-negative (DN) TGF-betaRII cDNA were generated. The in vivo effect of TGF-beta1 on RBM tumor growth and osteolysis was determined by histological and radiographic analysis, respectively, of athymic nude mice after intratibial injection of parental, empty vector, or DN RBM cells. The in vitro effect of TGF-beta1 on RBM cell growth was determined after TGF-beta1 treatment by MTT assay. RESULTS: TGF-beta1 and the TGF-beta receptors I and II (TGF-betaRI/II) were consistently expressed in both RBM tissues and cell lines. Inhibition of TGF-beta1 signaling in RBM cells significantly reduced tumor establishment and osteolysis observed in vivo after injection into the murine tibia, although no effect on tumor establishment was observed after injection of RBM cells subcutaneously or into the renal subcapsule. Treatment of five RBM cell lines with TGF-beta1 in vitro either had no effect (2/5) or resulted in a significant inhibition (3/5) of cell growth, suggesting that TGF-beta1 may promote RBM tumor growth indirectly in vivo. CONCLUSIONS: TGF-beta1 stimulation of RBM cells plays a role in promoting tumor growth and subsequent osteolysis in vivo, likely through the initiation of tumor-promoting paracrine interactions between tumor cells and the bone microenvironment. These data suggest that inhibition of TGF-beta1 signaling may be useful in the treatment of RBM. 相似文献
53.
54.
Michael W Ross Amy Jo Harzke Deborah P Scott Kelly McCann Michael Kelley 《AIDS education and prevention》2006,18(6):504-517
We report select outcomes from an evaluation of Project Wall Talk, a community-based, peer-led HIV prevention education program implemented in 36 Texas State prison units. Peer educators completed questionnaires prior to receipt of a 40-hour intensive training (N = 590) and at 9-month follow-up (N = 257). Students (N = 2506) completed questionnaires pre- and post-receipt of peer educator-led HIV education sessions. Peer educators and their students showed significant increases in HIV-related knowledge. Peer educators showed significant increases in assessment of their skills as educators. For both peer educators and students, significant differences in HIV-related knowledge were indicated across categories of prior educational level attained and race/ethnicity; no such differences were indicated at follow-up. Compared with baseline, a significantly greater proportion of peer educators reported ever having had an HIV test. After receiving peer-led education, a significantly smaller proportion of students reported they knew their HIV status and more indicated plans to take an HIV test. Additionally, in months 12 and 18 following program implementation, the numbers of HIV tests at the five units that implemented the peer education program were roughly twice that of five, matched comparison units without the peer education program. Based on peer educator reports, we projected that peer educators (N = 257) may have as many as 84,000 or more annual opportunities to share HIV-related knowledge with other prisoners outside the classroom. 相似文献
55.
Alexander L Green Erlick A C Pereira Dominic Kelly Peter G Richards Michael G Pike 《Journal of clinical neuroscience》2007,14(11):1049-1054
All 253 children receiving neurosurgical intervention for hydrocephalus (HCP) at a single British Neurosurgical Unit over a decade were investigated by retrospective case note review. Referral rates and mean age at presentation remained stable throughout, as did proportions of children presenting due to myelomeningocoele or meningitis. Comparing the first and second halves of the decade, the predominant aetiologies (intraventricular haemorrhage [IVH] at <1 year and brain tumour at 1-16 years) reduced from comprising half (70/129) of all cases to just over one-third (43/124). Other significant changes included a 45% reduction in neonatal IVH and a 179% increase in rare miscellaneous disorders. Outcome after 4 years of follow-up for all patients showed 44.4% without deficit, 11.9% with non-cognitive neurological deficits only, 11.5% with cognitive impairment only, 13.5% with both cognitive and neurological impairments, and 15.5% mortality. 相似文献
56.
R K Conlee D W Barnett K P Kelly D H Han 《Metabolism: clinical and experimental》1991,40(10):1043-1047
Cocaine and exercise are both known as stressors, but little is known about the combined effects of these two treatments. In this study, rats under the influence of cocaine (12.5 mg/kg, intraperitoneally [IP]) or saline were exposed to a variety of resting conditions, as well as exercise (running, 26 m/min, 10% grade, for 30 minutes), to evaluate the amount of stress imposed by these conditions as determined by the changes in the plasma concentrations of corticosterone (C) and catecholamines (norepinephrine [NE], epinephrine [E], dopamine [DA]). After injection of saline, resting near the operating treadmill for 30 minutes caused the concentration of C to increase from 0.07 +/- 0.03 to 0.30 +/- 0.05 microgram/mL (P less than .05), compared to the increase to only 0.15 +/- 0.04 micrograms/mL after resting in a cage. This increase due to proximity to the treadmill subsided after 50 minutes. After cocaine, the 30-minute resting values were 0.70 +/- 0.15 (treadmill) and 0.55 +/- 0.13 (cage) (P less than .05), and did not subside after 50 minutes. Cocaine also increased levels of E, NE, and DA above those in saline under all rest conditions. With exercise, the value for C in saline increased to 0.61 +/- 0.18, but, in cocaine, the value went to 0.93 +/- 0.05 (P less than .05). The concentrations of E (946 +/- 74 v 603 +/- 101 pg/mL, cocaine v saline) and NE (1,027 +/- 102 v 440 +/- 153, cocaine v saline) during exercise also were exaggerated by cocaine treatment (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
57.
Scott W. Powers Kelly C. Byars Monica J. Mitchell Susana R. Patton Teresa Schindler Margaret H. Zeller 《Children's Health Care》2003,32(4):297-311
This pilot study examined a behavioral treatment to increase calorie intake in toddlers with cystic fibrosis. Eight toddlers were randomly assigned to behavioral plus nutrition (BEH) or nutrition intervention (NTR) conditions. Calorie intake and weight were measured at pre- and posttreatment. The BEH group showed a trend for changes in calorie intake pre- to posttreatment (p = .07; 40% increase). Results for the BEH and NTR groups did not differ significantly. Most participants achieved weight gains consistent with normal growth. Seventy-five percent had not shown this pattern during the year prior to intervention. These results support the feasibility and potential for behavioral interventions in this age group. 相似文献
58.
59.
The correct timing of surgery in cases of gallstone pancreatitis is debatable. To delineate more clearly the influence of the timing of surgery in the treatment of the disease, a prospective randomized clinical study of early surgery (less than 48 hours after admission) and delayed surgery (more than 48 hours after admission) was conducted in 165 patients. Ranson's prognostic signs of severity of disease were used to classify the patients into two risk groups: mild pancreatitis (three or fewer positive signs) and severe pancreatitis (more than three positive signs). In patients with three or fewer positive Ranson's signs, the time of surgery appeared to have little effect on the outcome, whereas in patients with more than three positive signs, early surgery resulted in a significant increase in rates of morbidity and mortality. Controlled randomization showed that in patients with gallstone pancreatitis, edematous or hemorrhagic necrotizing pancreatitis can develop, with or without impacted stones, early or late in the progression of the disease, during early or delayed surgery. These findings suggest that (1) although a gallstone initiates a bout of pancreatitis, it does not cause the progression of the disease; (2) the fate of the progression of pancreatitis is decided early by the amount of digestive enzymes being activated; (3) early removal of an impacted stone does not ameliorate the progression of pancreatitis; and (4) surgery should be performed during the initial hospital admission after the pancreatitis has subsided. 相似文献
60.
Prolactin and growth hormone receptors 总被引:2,自引:0,他引:2