To determine whether mononuclear cell secretory products contribute to the changes in bone turnover that characterize the development of postmenopausal osteoporosis, we evaluated the effects of oophorectomy and subsequent estrogen replacement on the spontaneous secretion of interleukin 1 (IL-1) and tumor necrosis factor a (TNF-a) and on the phytohemagglutinin A-induced secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) from peripheral blood mononuclear cells. In 15 healthy premenopausal women who underwent oophorectomy, increases in GM-CSF activity were observed as early as 1 week after surgery, whereas elevations in IL-1 and TNF-a and in hydroxyproline/creatinine and calcium/creatinine ratios, two urinary indices of bone resorption, were detectable 2 weeks after the surgical procedure. Six of the oophorectomized women received no estrogen therapy after surgery and in these subjects hydroxyproline/creatinine and calcium/creatinine ratios plateaued 6 weeks postoperatively, and all three cytokines reached the highest levels 8 weeks after oophorectomy, when the study ended. In the remaining 9 women, who were started on estrogen replacement therapy 4 weeks after oophorectomy, decreases in the indices of bone resorption paralleled decreases in the secretion of the cytokines, with lower levels detected after 2 weeks of therapy. In the women who did not receive estrogen therapy, circulating osteocalcin, a marker of bone formation, increased beyond preoperative levels 8 weeks after oophorectomy, whereas in the estrogen-treated subjects osteocalcin remained unchanged in the entire study period. In 9 female controls who underwent simple hysterectomy, cytokine release and biochemical indices of bone turnover did not change after surgery. These data indicate that changes in estrogen status in vivo are associated with the secretion of mononuclear cell immune factors in vitro and suggest that alterations in the local production of bone-acting cytokines may underlie changes in bone turnover caused by surgically induced menopause and estrogen replacement.Postmenopausal osteoporosis, a common disorder characterized by a decreased bone mass and increased fracture risk (1), stems from an accelerated loss of bone that begins after natural or surgically induced menopause and progresses rapidly for 5 or 10 years thereafter (2, 3). That estrogen deficiency plays a major role in this condition is well supported by the higher prevalence of osteoporosis in women than in men (4), by the increase in the rate of bone mineral loss detectable by bone densitometry after artificial or natural menopause (5, 6), and by the protective effect of estrogen replacement with respect to both bone mass loss and fracture incidence (7,8). Although the bone-sparing effect of estrogen appears to be related to an inhibitory effect on bone resorption (9), the mechanism of the estrogen response remains unknown.The discovery of estrogen receptors in osteoblasts (10-12) and osteoclasts (13) suggests that a direct mechanism(s) may be in...

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Objective: The objective of the study was to evaluate anti-factor Xa levels with therapeutic enoxaparin anticoagulation in pregnancy.Study Design: A total of 15 pregnant subjects on therapeutic doses of enoxaparin (1 mg/kg ±20% subcutaneously (s.c.) twice daily (b.i.d.)) were enrolled prospectively in this cross-sectional pilot project. Three blood levels for anti-factor Xa activity were examined: before the enoxaparin dose (trough), 3-to 4-h later (peak) and 8-h later. Anti-factor Xa activity level between 0.5 and 1.2 U/ml was considered therapeutic.Result: Mean anti-factor Xa activity levels were: trough 0.45±0.18, peak 0.9 ± 0.25 and 8-h after dose 0.72 ± 0.23 U/ml. All peak levels were therapeutic; 20% (3/15) of the 8 h and 73% (11/15) of the trough levels were sub-therapeutic.Conclusion: Trough and 8-h post-dose anti-factor Xa activity levels were sub-therapeutic in a substantial number of patients receiving a b.i.d. regimen of therapeutic enoxaparin.

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The metabolic clearance rate (MCR) and the production rate (PR) of testosterone were measured in four male subjects by the method of constant infusion of tritiated testosterone. The mean value of the MCR of 1161 ± 80 (SD) liters/24 hours was not altered by the infusion of epinephrine, at the rate of 0.466 mg per hour for three: hours. The plasma testosterone concentration was measured by the double isotope method of Riondel et al. (1963). Epinephrine significantly decreased this concentration (28%) and also the production rate (28%) The effect of epinephrine on plasma testosterone concentration was measured in six additional male subjects, and the results of the total of 10 subjects showed that there was a decrease of (28%) in the concentration. It was concluded that epinephrine significantly diminished the production rate of testosterone.

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