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Bazedoxifene (Conbriza®, Viviant®) is the first third-generation selective estrogen receptor modulator (SERM) and it is approved for the treatment of postmenopausal osteoporosis in the EU and Japan. Bazedoxifene contains an indole-based core binding domain that binds with high affinity to estrogen receptors and exhibits favourable effects on bone and lipid profiles, with no clinically relevant endometrial or breast stimulation. Oral bazedoxifene once daily reduced the incidence of new vertebral fractures in patients with postmenopausal osteoporosis in a large, well designed trial of 3 years' duration; both bazedoxifene and raloxifene were significantly more effective than placebo. Neither bazedoxifene nor raloxifene reduced the incidence of nonvertebral fractures in the overall study population; however, bazedoxifene, but not raloxifene, reduced the rate of nonvertebral fractures in high- risk patients. Moreover, data from patients who continued to receive the drug during a 2-year extension phase of this trial indicate that bazedoxifene continues to provide protection against new vertebral fractures for up to 5 years. Bazedoxifene also increases bone mineral density and reduces the levels of bone turnover markers. Bazedoxifene was generally well tolerated and did not detrimentally affect the reproductive tract or breast tissue in clinical trials, thereby demonstrating a favourable risk-benefit profile. A pharmacoeconomic analysis conducted from an EU perspective predicted bazedoxifene to be cost effective in some EU countries. Therefore, bazedoxifene presents another useful option for the treatment of postmenopausal osteoporosis, especially in those at high risk for osteoporotic fracture. [ABSTRACT FROM AUTHOR]

Objective To examine the effect of intravaginal dehydroepiandrosterone (DHEA) on pain at sexual activity (dyspareunia) identified as the most bothersome symptom of vaginal atrophy in postmenopausal women at both screening and day 1. Methods This prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of prasterone (DHEA) applied locally in the vagina on the severity of dyspareunia in 114 postmenopausal women who had identified dyspareunia as their most bothersome symptom of vaginal atrophy, while meeting the criteria for superficial cells ≤≤ 5%% and pH > 5.0 at both screening and day 1. Results At the standard duration of 12 weeks of treatment, increasing doses of 0.25%%, 0.5%% and 1.0%% DHEA decreased the percentage of parabasal cells by 48.6 ±± 6.78%%, 42.4 ±± 7.36%% and 54.9 ±± 6.60%% ( p < 0.0001 vs. placebo for all) with no change with placebo ( p == 0.769). The effects on superficial cells and pH were also highly significant compared to placebo at all DHEA doses. The severity score of pain at sexual activity decreased by 0.5, 1.4, 1.6 and 1.4 units in the placebo and 0.25%%, 0.5%% and 1.0%% DHEA groups, respectively, with the p value of differences from placebo ranging from 0.0017 to < 0.0001. Conclusions Intravaginal DHEA, through local estrogen and androgen formation, causes a rapid and highly efficient effect on pain at sexual activity without systemic exposure of the other tissues, thus avoiding the recently reported systemic effects of estrogens. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor alpha (PPARα) ligands are medications used to treat hyperlipidaemia and atherosclerosis. Increasing evidence suggests that these agents are immunosuppressive. In the following studies we demonstrate that WY14,643, a PPARα ligand, attenuates expression of anti-glomerular basement membrane disease (AGBMD). C57BL/6 mice were fed 0·05% WY14,643 or control food and immunized with the non-collagenous domain of the α3 chain of Type IV collagen [α3(IV) NC1] in complete Freund's adjuvant (CFA). WY14,643 reduced proteinuria and greatly improved glomerular and tubulo-interstitial lesions. However, the PPARα ligand did not alter the extent of IgG-binding to the GBM. Immunohistochemical studies revealed that the prominent tubulo-interstitial infiltrates in the control-fed mice consisted predominately of F4/80+ macrophages and WY14,643-feeding decreased significantly the number of renal macrophages. The synthetic PPARα ligand also reduced significantly expression of the chemokine, monocyte chemoattractant protein (MCP)-1/CCL2. Sera from mice immunized with AGBMD were also evaluated for antigen-specific IgGs. There was a significant increase in the IgG1 : IgG2c ratio and a decline in the intrarenal and splenocyte interferon (IFN)-γ mRNA expression in the WY14,643-fed mice, suggesting that the PPARα ligand could skew the immune response to a less inflammatory T helper 2-type of response. These studies suggest that PPARα ligands may be a novel treatment for inflammatory renal disease. [ABSTRACT FROM AUTHOR]

A 21-year-old Arab gelding with clinical signs of acute peritonitis had a perforating ulcer on the mesenteric border of the jejunum which resulted in localised contamination of the abdomen with ingesta. The affected segment of jejunum was resected and the abdomen was lavaged extensively. Postoperatively, the gelding was treated with broad-spectrum antibiotics, non-steroidal anti-inflammatory drugs and intravenous fluids, but after four days it became acutely non-weight bearing on its right hindlimb, and a tendonitis of the lateral digital flexor tendon within the tarsal sheath was identified ultrasonographically. The septic tendonitis was treated with broad-spectrum antibiotics but progressed proximodistally within the tendon until it involved both the tarsal sheath and the associated tarsocrural joint, necessitating the euthanasia of the gelding. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to evaluate the effects on hemostatic factors of a low-dose preparation of levonorgestrel and ethinyl estradiol in a 12-cycle study.Study Design: Thirty healthy women began taking 100 microg levonorgestrel and 20 microg ethinyl estradiol on the first day of the menstrual cycle, continued to take the preparation for the next 21 days, and then took placebo for 7 days. Mean changes in prothrombin time, partial thromboplastin time, and levels of factors VII and X, antithrombin, plasminogen, fibrinogen, protein S, thrombin-antithrombin complexes, and D-dimer were analyzed at baseline and at cycles 3, 6, and 12 with paired Student t tests.Results: Factor X, plasminogen antigen and activity, and D-dimer levels were significantly increased (P Conclusion: The effects on hemostatic factors in healthy women of a monophasic preparation of 100 microg levonorgestrel and 20 microg ethinyl estradiol were similar to those of other low-dose oral contraceptives. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to evaluate the efficacy and safety of 3 dosages of Esclim, delivering 0.025 mg, 0.050 mg, or 0.100 mg 17beta-estradiol per 24 hours, in the treatment of moderate to severe vasomotor symptoms.Study Design: In this double-blind, placebo-controlled, parallel-group, multicenter trial, 196 highly symptomatic menopausal women received 12 weeks of continuous unopposed treatment with 1 of the 3 dosages of Esclim or a matching placebo patch.Results: The reduction in frequency of moderate to severe vasomotor symptoms was statistically significant compared with placebo (P <.05) from week 2 onward in the Esclim 50 and 100 groups and from week 3 onward in the Esclim 25 group. Symptom severity was also reduced. Estrogen-related adverse events, particularly metrorrhagia and endometrial hyperplasia, were less frequent in the Esclim 25 group than in the higher-dosage groups.Conclusion: All 3 dosages of Esclim were effective in the treatment of vasomotor symptoms. The efficacy and safety of Esclim 25 indicate a good risk-benefit ratio. [ABSTRACT FROM AUTHOR]

This is a review of 21 patients with meningiomas involving the region of the cavernous sinus. All underwent surgery, and the fronto-zygomatic (F-Z) approach, first described by Fujitsu and Kubawara, was employed in every case. The mean age at presentation was 47 years; seven patients were male and 14 female. The mean duration of symptoms before surgery was 4 years. In 10 patients, resection was considered to be complete. Peri-operatively there were two deaths, but the majority of deficits in the survivors were temporary and quickly resolved. The mean follow-up period was 48 months. In that time, five patients experienced recurrence or progression of tumour, of whom three required repeat operation (followed by radiotherapy); and two patients were referred for radiotherapy alone. These five patients appear to be disease-free 2-5 years after their additional treatment. Of the 19 patients who left hospital, 17 were able to live independent lives. It would appear from this review that: (1) F-Z craniotomy usually gives excellent exposure to the region of the cavernous sinus; (2) selected patients should undergo angiography with balloon occlusion to evaluate the collateral vascular supply; (3) regular review should include annual MRI. Evaluation over a much longer time of both surgery and radiotherapy, individually and in combination, is needed before it will be possible to furnish a treatment protocol for individual cases at initial presentation or recurrence. [ABSTRACT FROM AUTHOR]