Faculty Bibliography

CONTEXT: Despite the absence of progesterone receptor protein in human endometrial endothelial cells (HEECs), endometria of women receiving long-acting progestin-only contraceptives (LAPCs) display reduced uterine blood flow, elevated reactive oxygen species generation, increased angiogenesis, and irregularly distributed, enlarged, fragile microvessels resulting in abnormal uterine bleeding. OBJECTIVE: We propose that paracrine factors from LAPC-treated human endometrial stromal cells (HESCs) impair HEEC functions by shifting the balance between HEEC viability and death in favor of the latter. DESIGN AND SETTING: Proliferation, apoptosis, and transcriptome analyses were performed in HEECs treated with conditioned medium supernatant (CMS) derived from HESCs treated with estradiol (E2) +/- medroxyprogesterone acetate or etonogestrel under normoxia or hypoxia. Mass spectrometry interrogated the CMS secretome while immunostaining for neuronal pentraxin-1 (NPTX1), cleaved caspase-3, and cytochrome c was performed in cultured HEECs and paired endometria from women using LAPCs. MAIN OUTCOME: HEEC apoptosis and its underlying mechanism. RESULTS: HESC CMS from E2 + medroxyprogesterone acetate or E2 + etonogestrel incubations under hypoxia induced HEEC apoptosis (P < .05), whereas mass spectrometry of the CMS revealed increased NPTX1 secretion (P < .05). Endothelial cleaved caspase-3 and stromal NPTX1 immunoreactivity were significantly higher in LAPC-treated endometria (P < .001). Transcriptomics revealed AKT signaling inhibition and mitochondrial dysfunction in HEECs incubated with HESC CMS. In vitro analyses proved that CMS decreased HEEC AKT phosphorylation (P < .05) and that recombinant NPTX1 (P < .05) or NPTX1 + H2O2 (P < .001) increase HEEC apoptosis and cytosolic cytochrome c levels. CONCLUSIONS: LAPC-enhanced NPTX1 secretion and reactive oxygen species generation in HESCs impair HEEC survival resulting in a loss in vascular integrity, demonstrating a novel paracrine mechanism to explain LAPC-induced abnormal uterine bleeding.

The enhanced palpebral spring and the gold weight are the modern devices that should nearly completely replace tarsorrhaphy in the management of ocular problems secondary to facial paralysis. They actually reanimate the lid, rather than merely hold the lids closed in a disfigured position, as does tarsorrhaphy. The surgical techniques of each procedure, results, and pros and cons of each are compared. Personal experience with over 1400 spring implantations is discussed, as is experience with the use of bandage contact lenses in lieu of lid surgery. The gold weight implantation is simpler to learn and perform than the enhanced spring procedure, in which the levator is tightened in addition to implanting the spring. However, when it is really important to close the eye well, the spring is the superior procedure. Unlike the weight, the spring closes the eye well in the supine position, such as when the patient sleeps