Inflammatory cytokines differentially up-regulate human endometrial haptoglobin production in women with endometriosis.

BACKGROUND: Evidence suggests that eutopic endometrium from women with endometriosis (US-E) has intrinsic functional anomalies compared with women without endometriosis (US-C). We hypothesized that differences in endometrial haptoglobin (eHp) mRNA and protein levels exist between eutopic endometrium from US-E and US-C and that inflammatory mediators may be involved. METHODS: Endometrial stromal cells and tissue explants from US-E (n = 18) and US-C (n = 18) were cultured (24 h/48 h for cells/explants) with interleukin (IL)-1alpha, -1beta, -6, -8 or tumor necrosis factor-alpha (TNF-alpha) at 0-100 ng/ml. eHp protein in media and mRNA levels were quantified by enzyme-linked immunosorbent assay and quantitative PCR. RESULTS: In eutopic endometrial stromal cells from US-E, IL-1beta, IL-6 and TNF-alpha (10 ng/ml) increased eHp mRNA levels (P = 0.002, P < 0.001 and P < 0.001, respectively) and eHp protein (P = 0.023, 0.031 and 0.006, respectively) versus control. In endometrial tissues from US-E, IL-1beta, IL-6 and TNF-alpha increased eHp mRNA (P < 0.001, P = 0.017 and P < 0.001, respectively) and eHp protein (P < 0.001, P = 0.007 and 0.039, respectively) versus control. IL-1alpha and IL-8 had small or no effects on isolated endometrial cells or tissues. In US-C, IL-1beta, IL-8 and TNF-alpha each reduced eHp mRNA in endometrial stromal cells (all P < 0.001) versus control; IL-1alpha and IL-6 had no effect. eHp mRNA increased in endometrial tissues from US-C in response to IL-1beta (P = 0.008), IL-6 (P = 0.015) and TNF-alpha (P = 0.031) versus control; IL-1alpha or IL-8 had no effect. CONCLUSIONS: Endometrium from US-E differentially responds to specific inflammatory cytokines by production of eHp. We propose that up-regulation of endometrial eHp by inflammatory mediators disrupts normal endometrial function and may facilitate the pathogenesis of endometriosis.

Syndrome of inappropriate secretion of antidiuretic hormone secondary to fluoxetine.

OBJECTIVE: To report a case of possible fluoxetine-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH). CASE SUMMARY: A 92-year-old patient was prescribed oral fluoxetine 20 mg daily for depression. After 13 days of therapy, she developed severe weakness and was found to have hyponatremia. Fluoxetine was discontinued. Treatment included fluid restriction and sodium chloride and potassium supplementation. Eight days after admission, the hyponatremia resolved and the patient was discharged without any pharmacologic treatment for depression. DISCUSSION: Case reports on fluoxetine-induced SIADH were reviewed. Fluoxetine-associated SIADH appears to occur most commonly after short-term therapy in elderly patients. Resolution of hyponatremia occurs six days to two weeks after discontinuation of fluoxetine. CONCLUSIONS: Geriatric patients receiving fluoxetine should be monitored regularly to detect abnormal electrolyte values.

Medication compliance in elderly outpatients using twice-daily dosing and unit-of-use packaging.

OBJECTIVE: To determine the effect of unit-of-use drug packaging of medications on compliance among elderly outpatients treated with complex medication regimens. DESIGN: Nonblind, randomized, clinical trial. SETTING: Geriatric outreach health centers in urban public housing units for independent-living elderly people. PATIENTS: Thirty-one patients (aged > or = 60 y), each taking three or more prescribed medications. Patients were randomly assigned to one of three study groups: group 1 (n = 12), no change in dosing or packaging; group 2 (n = 10), conventional packaging with twice-daily dosing; group 3 (n = 9), unit-of-use packaging with twice-daily dosing. INTERVENTION: A unit-of-use package consisting of a two-ounce plastic cup with a snap-on lid containing all medications to be taken at the time of dosing. MAIN OUTCOME MEASURES: Medication compliance was assessed monthly for six months using tablet counts. RESULTS: Medication compliance was significantly better in group 3 (92.6 percent) using unit-of-use packaging compared with either group 1 (79 percent) or group 2 (82.6 percent) (p = 0.017). Compliance did not differ between groups 1 and 2. CONCLUSIONS: In this small study of elderly outpatients taking three or more medications, unit-of-use packaging and twice-daily dosing improved medication compliance compared with conventional packaging.