The Effects of Nitroglycerin on the Oxytocin Dose-Response Profile in Oxytocin-Desensitized and Naïve Human Myometrium: An In Vitro Study.

BACKGROUND: Nitroglycerin is used for acute reduction in uterine tone. Prolonged oxytocin exposure causes desensitization of oxytocin receptors. It is unknown if nitroglycerin exposure impacts the subsequent action of oxytocin in the setting of oxytocin receptor desensitization. This study investigated the effects of nitroglycerin on oxytocin-desensitized and oxytocin-naïve human myometrium and the subsequent response to oxytocin dose-response testing in vitro. METHODS: Myometrial samples from 17 elective cesarean deliveries were divided into strips and allocated to 1 of 4 groups: (1) oxytocin desensitized and no nitroglycerin; (2) oxytocin desensitized and nitroglycerin; (3) oxytocin naïve and nitroglycerin; and (4) oxytocin naïve and no nitroglycerin. Final analysis included 28 strips per group. Nitroglycerin groups were exposed to incremental concentrations of nitroglycerin, while no nitroglycerin groups were kept in control (physiological salt) solution. All groups then underwent oxytocin dose-response testing. Primary outcome was motility index (amplitude × frequency; grams × contractions per 10 minutes [g·c/10 min]). Secondary outcomes were amplitude (g), frequency (contractions/10 minutes), and area under the curve (g·s). All outcomes (nitroglycerin and oxytocin dose-response periods) were expressed as a percentage change from baseline. Values were log transformed, compared using regression modeling and reported as the ratio of 2 geometric means (relative difference). RESULTS: No significant difference was observed in motility index following nitroglycerin administration in oxytocin-desensitized versus oxytocin-naïve groups (relative difference = 19.0%; 95% confidence interval [CI], -32.6 to 109.9; P = .55). On oxytocin dose-response testing, motility index was highest in oxytocin-naïve and no nitroglycerin samples (group 4) (1.356 g·c/10 minutes) followed by oxytocin-naïve and nitroglycerin (group 3) (0.882 g·c/10 minutes), oxytocin-desensitized and no nitroglycerin (group 1) (0.769 g·c/10 minutes), and oxytocin-desensitized and nitroglycerin (group 2) (0.651 g·c/10 minutes) samples. Motility index was significantly reduced in group 1 vs 4 (relative difference = -43.3%; 95% CI, -66.5 to -4.1; P = .034) and group 2 vs 4 (relative difference = -52.0%; 95% CI, -70.9 to -20.8; P = .004). While in groups 3 vs 4, both amplitude (relative difference = -17.8%; 95% CI, -30.9 to -2.2; P = .27) and area under the curve (AUC; relative difference = -17.5%; 95% CI, -30.7 to -1.8; P = .030) were reduced. CONCLUSIONS: Nitroglycerin-induced relaxation was not different between oxytocin-desensitized and oxytocin-naïve human myometrial strips in vitro. However, oxytocin-induced contractility was attenuated after nitroglycerin exposure in both oxytocin-desensitized and oxytocin-naïve samples, with maximum attenuation observed in desensitized tissues. This finding warrants further clinical studies to explore uterine responsiveness to oxytocin in women with oxytocin-augmented labors after nitroglycerin administration.

Patient preference survey in the management of asymptomatic carotid stenosis.

OBJECTIVES: Carotid stenosis accounts for 20% of ischemic strokes and can be managed with pharmacotherapy alone or in conjunction with carotid endarterectomy or stenting. The management of asymptomatic carotid stenosis is controversial amongst physicians. The aim of this study was to explore patient preferences for the potential management options using a standardized scenario to minimize clinician bias. These data will then be used to facilitate comparison with existing published data on physicians' preferences in the management of asymptomatic carotid stenosis. METHODS: A patient information booklet and questionnaire was developed, validated, and distributed to patients who were identified as candidates for carotid screening duplex based on the presence of peripheral arterial, coronary, or aneurismal disease. Patients were asked to imagine their duplex revealed a 70% unilateral carotid stenosis. Five-year stroke or death risks of 11% were quoted for best medical therapy. The perioperative stroke or death rates quoted were 3% for endarterectomy and 3% to 5% for stenting, based on best current evidence. No physician interaction was allowed to minimize clinician bias. Responses for treatment preference and reasoning were analyzed using appropriate statistical methods. Results from this survey were then compared with a previously published poll of physician preference. RESULTS: One hundred two questionnaires were analyzed with a 94% response rate: 48% chose pharmacotherapy alone, 30% selected carotid endarterectomy, and 22% opted for stenting. The preference for pharmacotherapy alone over either intervention, and for endarterectomy, over stenting was consistent in subgroup analyses by age, gender, prior stroke, family history of stroke, and smoking status. CONCLUSION: In this scenario, patients were split equally between medical and surgical treatment of asymptomatic carotid stenosis. This was identical to a recent poll of physicians. Tools for risk assessment and the results of the SPACE2, ACST2, and ACT1 trials would benefit patients and physicians making this important treatment decision.

Progestational agents for the prevention of preterm birth.

Abstract In a risk/benefit analysis, currently the use of PAs used in women with a previous history of PTB appears to be worthwhile though the impact on the PTB rate may be minor since 80-90% of women who deliver preterm have no past history. PTB is a heterogeneous condition. With the exception of extremes of gestational age, PTB is due in equal parts to SPTL, preterm prelabour rupture of the membranes (PPROM) and elective PTB for fetomaternal indications. The assessment of the use of PAs to prevent PTB should only relate to previous and subsequent SPTL and not to PTB due to fetomaternal indications.

Effect of cell shape and packing density on granulosa cell proliferation and formation of multiple layers during early follicle development in the ovary.

The postnatal mouse ovary is rich in quiescent and early-growing oocytes, each one surrounded by a layer of somatic granulosa cells (GCs) on a basal lamina. As oocytes start to grow the GCs change shape from flattened to cuboidal, increase their proliferation and form multiple layers, providing a unique model for studying the relationship between cell shape, proliferation and multilayering within the context of two different intercommunicating cell types: somatic and germ cells. Proliferation of GCs was quantified using immunohistochemistry for Ki67 and demonstrated that, unusually, cuboidal cells divided more than flat cells. As a second layer of GCs started to appear, cells on the basal lamina reached maximum packing density and the axes of their mitoses became perpendicular to the basal lamina, resulting in cells dividing inwards to form second and subsequent layers. Proliferation of basal GCs was less than that of inner cells. Ultrastructurally, collagen fibrils outside the basal lamina became more numerous as follicles developed. We propose that the basement membrane and/or theca cells that surround the follicle provide an important confinement for rapidly dividing columnar cells so that they attain maximum packing density, which restricts lateral mitosis and promotes inwardly oriented cell divisions and subsequent multilayering.