The role of the IGFs and IGFBPs on age-related changes in BMD in adult men and women is not well understood. Studying an age-stratified community based sample of 344 men and 276 women, we found higher IGFBP-2 levels to be associated with lower BMD. IGFBP-2, which increases with age in both men and women, was the strongest, most consistent predictor of BMD among the IGF/IGFBPs studied. INTRODUCTION: Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators of tissue growth and metabolism, but their association with BMD in adult men and women is controversial. MATERIALS AND METHODS: In an age-stratified, random sample of the community population, we examined the role of serum levels of IGF-I, IGF-II, and IGFBP-1, -2, and -3 on BMD of the proximal femur (total hip), lateral spine, midshaft, and ultradistal radius as measured by DXA. We explored the association before and after adjustment for potential confounders, including age, bioavailable estradiol and testosterone, sex hormone binding globulin (SHBG), and measures of total fat and skeletal muscle mass. RESULTS: We studied 344 men (age, 23-90 years) and 276 women (age, 21-93 years; 166 postmenopausal) not on hormone replacement or oral contraceptives. In both men and women, IGF-I and IGFBP-3 levels fell with advancing age, whereas IGFBP-2 levels tended to rise with age. There was an inverse association of IGFBP-2 with BMD at most skeletal sites in men and both premenopausal and postmenopausal women, whereas lower IGF-I and IGFBP-3 were associated with lower BMD in men and postmenopausal women only. Lower IGF-II was associated with lower BMD in men only. There were no associations between IGFBP-1 and BMD in either sex. After adjustment for age, in most cases, we found no further associations between IGF-I, IGF-II, or IGFBP-3 and BMD. In contrast, after age adjustment, higher IGFBP-2 remained a predictor of lower BMD in men and postmenopausal women at all sites except for the lateral spine (for men: r = -0.21, -0.20, and -0.19, all p < 0.001; and for postmenopausal women: r = -0.34, -0.24, and -0.25, all p < 0.01, for the total hip, midshaft, and ultradistal radius, respectively). IGFBP-2 remained an independent negative predictor of BMD in men, postmenopausal women, and all women combined after additional adjustment for bioavailable sex steroids, but not at all sites after adjustment for SHBG and muscle mass. In premenopausal women, IGFBP-2 had similar associations as seen in postmenopausal women, but they were weaker and not statistically robust. CONCLUSIONS: Among the IGF/IGFBPs in our study, IGFBP-2 was a key negative predictor of BMD among men and women, particularly postmenopausal women. Our findings suggest a potential role of the IGF/IGFBP system in regulating bone loss in aging men and women and identify a previously under-recognized, potentially deleterious role for IGFBP-2, a known inhibitor of IGF action that increases with age in both sexes. Whether the action of the IGF/IGFBP system on bone metabolism is mediated partly through its effects on muscle mass or SHBG deserves further study. 相似文献
Previous work has shown that alterations in proteoglycan aggregates are among the first changes detected with aging, disuse, and degeneration of articular cartilage, yet the cause or causes of these alterations remain unknown. To determine if differences in link protein concentration can explain alterations in the assembly, size, and stability of articular cartilage proteoglycan aggregates, we isolated proteoglycan monomer (aggrecan) and link protein from adult bovine articular cartilage and then assembled proteoglycan aggregates from aggrecan and 0.8% hyaluronan relative to aggrecan weight, in the presence of 0, 2, 4, 6, 8, 10, 15, and 20% concentrations of link protein relative to aggrecan weight. We determined the amount, sedimentation coefficient, and stability of the aggregates by analytical ultracentrifugation and measured their dimensions by electron microscopy with use of the monolayer technique. Increased aggregate size, as determined by ultracentrifugation, was directly correlated with an increased number of aggrecans per aggregate and with increased hyaluronan length, as determined by electron microscopy. The concentration of link protein significantly influenced aggregation: concentrations of 6–8% produced maximum aggregation, aggregate stability, and uniformity of aggrecan spacing; concentrations greater than 10% led to the formation of superaggregates (aggregates with sedimentation velocities greater than 100 S that may result from linking two or more hyaluronan filaments) but decreased aggregate stability; and concentrations of less than 4% link protein significantly decreased aggregation, the size and stability of aggregates, and the regularity of aggrecan spacing. The latter observations suggest that a decline in the concentration of link protein could decrease the organization and stability of the articular cartilage matrix. 相似文献
Background: Small doses of bupivacaine may be a reasonable choice for spinal anesthesia for patients having ambulatory surgery. However, few dose-response data are available to guide the selection of reasonable doses of bupivacaine for different ambulatory procedures.
Methods: Eight volunteers per group were randomized to receive 3.75, 7.5, or 11.25 mg of 0.75% bupivacaine with 8.25% dextrose in a double-blind manner. Sensory block was assessed with pinprick, transcutaneous electrical stimulation equivalent to surgical incision at the ankle, knee, pubis, and umbilicus, and with duration of tolerance to pneumatic thigh tourniquet. Motor block at the quadriceps and gastrocnemius muscles was assessed with isometric force dynamometry. Times until recovery from spinal anesthesia were recorded. Dose-response relationships were determined by linear regressions. Mean (95% confidence intervals) for durations of sensory and motor block per milligram of bupivacaine administered were calculated from linear regressions.
Results: Significant dose-response relationships (P < 0.006) were determined for sensory block, motor block, and time until recovery (R from 0.6 to 0.9). Within the range of doses studied, each additional milligram of bupivacaine was associated with an increase in duration of tolerance to transcutaneous electrical stimulation of 10 (7 to 13) min, an increase in tolerance to tourniquet of 7 (2 to 11) min, an increase in duration of motor block of 8 (5 to 12) min, and an increase in time until recovery of 21 (17 to 25) min. 相似文献
Summary: One hundred five women with a documented pregnancy of 41 weeks' gestation or more, admitted for induction of labour by balloon catheter with extra-amniotic saline instillation, were retrospectively compared to 196 women admitted in spontaneous labour at the same gestational age, with regard to mode of delivery. The success rate of the induction group was 97.1%. The mode of delivery did not differ significantly between the 2 groups. The Caesarean section rates were 11.4% in the induction group versus 9.7% in the spontaneous group. The mode of delivery after induction of labour by balloon catheter with extra-amniotic saline instillation and simultaneously commenced intravenous oxytocin infusion, in pregnancies of 41 weeks or more, is similar to that of spontaneous deliveries at the same gestational age. 相似文献
We determined how noninvasive presurgical data relate to prognosis after temporal lobectomy in patients with independent bilateral temporal lobe (IBTL) complex partial seizures on the intracranial electroencephalogram (EEG). Between 1986 and 1994, 28 patients had IBTL seizures on intracranial EEG. Fifteen of these 28 patients underwent temporal lobectomy and 13 were not offered surgery. Of the 15 patients who had surgery, 10 patients became seizure-free. Magnetic resonance imaging (MRI) and the Wada test were the only variables associated with a seizure-free outcome. Seven of 10 seizure-free patients had a lateralized Wada result or the presence of unilateral hippocampal sclerosis, whereas none of the patients with persistent seizures had either of these findings. Variables not found to be predictive of a seizure-free outcome included location of scalp interictal spikes, degree of seizure-onset laterality, presence of early epilepsy risk factor, duration of epilepsy, and full-scale intelligence quotient. We conclude that MRI and the Wada test provide information of prognostic value in patients with bilateral temporal seizures independent of intracranial EEG data. 相似文献
HLA-DR, DQ, and DP alleles were determined by restriction fragment length polymorphism (RFLP) and oligonucleotide hybridization analysis in 50 Caucasian children with pauciarticular juvenile rheumatoid arthritis (PaJRA) and 82 controls. There was an increased frequency of DR5, DRw8, and DQw4, as well as individual DQ alpha and beta chains, DQA*0401 and DQB1*0402, respectively, in this group of patients. There was an absolute association between DRw8, DQw4, DQA1*0401, and DQB1*0402 in the patient population. HLA-DPw2.1 was also increased in frequency. There was little evidence of linkage disequilibrium found between DPw2.1 and DR5, DRw8, or DQw4. These MHC Class II associations were more characteristic of those patients with young age of onset (less than 5 years), rather than those with onset greater than or equal to 5 years of age. Our data confirmed the previous associations of HLA-DR5, DRw8, and DPw2.1 with PaJRA and suggested a new association for DQ alpha and beta genes in the clinical expression of this disease. 相似文献
The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.Ms Doody and Drs Linet, Pottern, Boice, and Fraumeni are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Glass is with the Kaiser Permanente Medical Care Program, Northwest Region, Portland, Oregon, USA. Dr Friedman is with the Kaiser Permanente Medical Care Program, Northern California Region, Oakland, California, USA. Address correspondence to Ms Doody, Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 408, Bethesda, MD 20892, USA. This research was supported in part by National Cancer Institute contracts NO1-CP-01047, NO1-CP-01054, NO1-CP-11009, NO1-CP-11037, NO1-CP-31035, and NO1-CP-61006. 相似文献