Laparoscopic uterine suspension as an adjunctive procedure at the time of laser laparoscopy for the treatment of endometriosis.

Uterine suspension has been advocated as an adjunctive procedure at the time of conservative surgery for endometriosis but has seldom been used at the time of CO2 laser laparoscopic treatment of endometriosis. In this study of 225 patients treated for cul-de-sac endometriosis by CO2 laser laparoscopy between 1984 and 1989 uterine suspension was performed as an adjunctive procedure at the time of laparoscopy. The result was a cumulative pregnancy rate of 80.0%. Life-table analysis was performed, and monthly fecundity rates were calculated as 15.58%, 6.29%, 17.86% and 7.89% for Revised American Fertility Society (RAFS) endometriosis stages I to IV respectively. CO2 laser laparoscopy and laparoscopic uterine suspension alleviated preoperative pelvic pain complaints in 94% of the patients. Monthly fecundity rates for RAFS stage I endometriosis, which exceeded previously reported rates following expectant management, medical management and conservative surgery, were attributed to laparoscopic uterine suspension, which had not been previously reported as an adjunct to CO2 laser laparoscopy.

Use of DHCP to provide essential information for care and management of HIV patients.

The Department of Veterans' Affairs (VA) has reported over 10,000 Acquired Immune Deficiency Syndrome (AIDS) cases since the beginning of the epidemic. These cases were distributed throughout 152 of the VA's network of 172 medical centers and outpatient clinics. This network of health care facilities presents a unique opportunity to provide computer based information systems for clinical care and resource monitoring for these patients. The VA further facilitates such a venture through its commitment to the Decentralized Hospital Computer Program (DHCP). This paper describes a new application within DHCP known as the VA's HIV Registry. This project addresses the need to support clinical information as well as the added need to manage the resources necessary to care for HIV patients.

Osteoblast and osteoclast cell number and cell activity in postmenopausal osteoporosis.

This study evaluates osteoblast and osteoclast cell numbers and cell activities determined from quantitative histology of trabecular bone in human iliac crest bone biopsies. Subjects studied were postmenopausal osteoporotic patients (aged 53-81) for whom total body calcium and urine and serum clinical data were also available. Only 39% of the osteoclasts identified by acid phosphatase content were multinucleate; however, a significant correlation between multinucleate osteoclasts and the total number of osteoclasts was found (r = 0.87; p less than 0.001). The mean number of osteoclasts per square millimeter of total tissue area was 0.96 (+/- 0.14, SEM, n = 36); the mean number of osteoblasts was 6.8 (+/- 1.5, n = 14)/mm2 tissue area. Computed osteoclast activity (square millimeter bone resorbed per osteoclast nucleus per day) was 2.6 X 10(-4) +/- 1.0 X 10(-4) (n = 13). Computed osteoblast activity (square millimeter bone formed per osteoblast per day) was 2.9 X 10(-5) +/- 8.8 X 10(-6) (n = 13). Calculated mean rate of bone resorption was 1.6 X 10(-4) +/- 3.4 X 10(-5) mm2 bone resorbed per mm2 total tissue area per day (n = 19). These data indicate that although osteoclasts are not numerous in the iliac crest of postmenopausal osteoporotics, the individual osteoclast activity (in square millimeter bone resorbed osteoclast cell unit per day) is significantly greater (p less than 0.001) than the osteoblast activity (in square millimeter matrix deposited per cell per day). These data also point out that greater consideration should be given to the role that osteoclast cell activity may play in human postmenopausal osteoporosis.

Long-term calcitonin therapy in postmenopausal osteoporosis.

Results are presented from a 2-year controlled study evaluating the efficacy of 100 units synthetic salmon calcitonin/d in the treatment of postmenopausal osteoporosis. All patients received 400 units D2 po qd and 1200 mg CaCO3 po qd. The 21 control and 24 treated patients (mean age 65) were not statistically different at baseline. Although mean total body calcium (TBCa) was not significantly different between treated and control patients throughout the study, mean differences in the change in TBCa from baseline (treated minus control) were significant at 12, 18, and 26 months. The mean slope of TBCa for treated patients, but not for controls, was significantly positive through 18 months. Iliac crest bone biopsies showed (1) a significantly greater percent total bone area in treated compared to control patients at 2 years, and (2) a significantly decreased percent resorbing surface in treated patients when evaluated by paired difference from baseline. At 4 months, serum calcium values were significantly lower in treated patients than in controls (mean difference, treated minus controls), but were not statistically different from controls at study completion. Urine calcium increased significantly for the first 4 months in treated subjects and then declined to baseline levels. Since urinary calcium increased, the increase in TBCa was probably associated with an increase in net intestinal calcium absorption.

Stanozolol in postmenopausal osteoporosis: therapeutic efficacy and possible mechanisms of action.

To assess the efficacy of the anabolic steroid stanozolol in the treatment of osteoporosis, a 29-month double-blind study was performed with 23 treated and 23 control postmenopausal osteoporotic women. Drug efficacy was assessed by serial determinations of total body calcium (TBC--total bone mass) by neutron activation analysis, regional bone mass (RBM) by single-photon absorptiometry, and by spinal roentgenograms. Total body calcium increased 4.4% from baseline values (P less than 0.01) in the treated group and remained unchanged in the control group; the difference in the change in TBC between the treated and control groups was significant (P less than 0.03). The effect of the drug on TBC persisted throughout the 29-month period. In contrast to TBC, measurements of RBM indicated no significant differences between the treated and placebo groups, suggesting a possible differential response to therapy at various skeletal sites. No new spinal compression fractures were noted in the treated group (compared with three new fractures in the control group). Assessment of serum and urine values indicated a decrease in the level of urinary calcium and an increase in the level of total urinary cyclic AMP in the treated group. These changes were observed even though the level of serum iPTH was significantly decreased during the study. An analysis of changes in bone biopsy specimens revealed no significant differences between the treated and control groups. Seventy-six percent of the treated subjects developed SGOT elevations or other side effects from the stanozolol therapy; at no time were these effects sufficiently severe to cause termination of medication. The data suggest that long-term use of stanozolol increases the net total bone mass above pretreatment levels.

Deficient calcitonin response to calcium stimulation in postmenopausal osteoporosis?

To test whether mobilisation of immunoreactive calcitonin in response to calcium challenge is reduced in postmenopausal osteoporosis, seventeen postmenopausal osteoporotic women with compression fractures and ten normal age-matched women were given intravenous infusions of 3 mg/kg elemental calcium over a 10 min period. Blood samples were obtained 5 min before and at 0, 10, 20, and 60 min after start of infusion for the measurement of serum calcium and plasma immunoreactive calcitonin. Serum calcium increased significantly from baseline in both normal and osteoporotic groups; immunoreactive calcitonin increased significantly in the controls 10 min and 20 min after the start of infusion, but in the women with osteoporosis calcitonin levels did not change significantly at any time. 20 min after the start of infusion the change in immunoreactive calcitonin from baseline was significantly less in osteoporotic women than in the controls. These data are consistent with a decreased immunoreactive calcitonin response to calcium infusion in postmenopausal osteoporotic women, and suggest that calcitonin deficiency may be involved in the development of postmenopausal osteoporosis.

Increased immunoreactive calcitonin in idiopathic hypercalciuria.

Serum immunoreactive calcitonin concentration (iCT) was determined in nine subjects with idiopathic hypercalciuria (IH), prior to and during oral phosphate supplementation (500 mg qid) to test the hypothesis that a renal phosphate leak was the primary defect resulting in IH in these patients. Prior to the oral phosphate supplementation, serum iCT was significantly elevated in the IH group, when compared to 26 normal individuals (75 +/- 7 vs 45 +/- 4 pg/ml, mean +/- SE, P less than .001). During oral phosphate treatment, however, serum iCT decreased to levels not significantly different from normals (39 +/- 3 and 50 +/- 5 pg/ml after 4 and 8 weeks, respectively). When data prior to and during phosphate supplementation were pooled, there was a significant correlation (r = .70, N = 26, P less than .001) between serum iCT and serum calcium. These observations suggest that the increased serum iCT in these subjects was a response to slight elevations in serum calcium, which are the result of normal physiological mechanisms to correct the renal phosphate leak.

Stimulation of prostaglandin production in bone by phorbol diesters and melittin.

The production of prostaglandin E2 (PGE2) and bone resorption were studied in neonatal mouse calvaria in organ culture. Two tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and phorbol-12, 13-di-decanoate, but not the non-tumor promoters 4alpha-phorbol-12,13-didecanoate and phorbol, stimulated both PGE2 synthesis in bone and bone resorption. The effect of TPA was maximum at about 25 ng/ml, and half-maximum stimulation occurred at about 8 ng/ml TPA. The effects of TPA on the production of PGE2 and bone resorption were inhibited completely by indomethacin (5.6 X 10(-8) to 5.6 X 10(-7) M). The been venom toxin, melittin, was also a potent stimulator of prostaglandin synthesis in bone and bone resorption. The effect of melittin was maximum at about 25 ng/ml, and the dose-response curve was biphasic. The effects of melittin on the production of PGE2 and bone resorption were also inhbited by indomethacin. Indomethacin did not inhibit the bone resorption-stimulating activity of exogenously added PGE2. We conclude that phorbol diesters, which have irritant and tumor-promoting activity in mouse skin, and the polypeptide melittin can act directly on bone to stimulate resorption by a mechanism involving the local production of PGE2 or possible other indomethacin-inhibited metabolites odonic acid.

The effects of phosphate depletion on bone.

Phosphate depletion causes significant changes in the composition of the cell population in bone and the metabolic activities of these cells. The data presented indicate that a vitamin D metabolite has a significant role in producing the increase in osteoclast number associated with phosphate depletion. The increased resorptive activity and number of osteoclasts leads to a marked increase in the rate of bone resorption resulting in the liberation of calcium phosphate, while the decrease in the rates of the processes involved in bone formation (matrix production, osteoid maturation, and mineralization) reduces the amount of phosphate which is removed from the circulation. Thus, all of the effects of phosphate depletion on bone are consistent with the interpretation that bone acts as a reservoir of phosphate and is used to maintain soft tissue and serum phosphate levels at the expense of bone.

Bone resorption in organ culture: inhibition by the divalent cation ionophores A23187 and X-537A.

The ionophores A23187 and X-537A were used as probes to investigate the possible role of calcium uptake by bone as a mediator for the stimulation of bone resorption induced by parathyroid hormone (PTH) and other agents in cultured mouse calvaria. The ionophores alone at concentrations from 1 nM to 20 muM did not stimulate bone resorption, nor did they potentiate bone resorption stimulated by submaximal concentrations of PTH after either brief (15-60 min) or extended (1-3 day) exposure to the ionophores. Unexpectedly, we found that the ionophores inhibit in a dose-dependent manner bone resorption stimulated by PTH and a wide variety of other compounds (prostaglandin E2, 1alpha-hydroxycholecalciferol, 3-isobutyl-1-methyl-xanthine, and phorbol myristate acetate). This inhibition was not due to irreversible damage to the bones by the ionophores, because the inhibition was reversible even after 24 h of treatment. Inhibition of bone resorption by the ionophores was observed in media of both high and low calcium concentration, indicating that the inhibition was not due to a critical extracellular calcium concentration. Inhibition by the ionophores differs qualitatively in several ways from that produced by calcitonin, a natural inhibitor of bone resorption. Furthermore, A23187 at 1.0 mug/ml had no effect on the accumulation of cyclic AMP in the medium of either control, PTH- or calcitonin treated calvaria. We conclude that the ionophores A23187 or X537A do not stimulate bone resorption nor potentiate the effects of stimulators of bone resorption; instead they are inhibitors of bone resorption stimulated by a wide variety of compounds.