Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.
Glyburide's PK and PD have not been studied in women with gestational diabetes mellitus (GDM). The objective was to assess steady-state PK of glyburide as well as insulin sensitivity, beta-cell responsivity and overall disposition indices following a mixed meal tolerance test (MMTT) in GDM (n=40), non-pregnant type 2 diabetic (T2DM) (n=26) and healthy pregnant (n=40, MMTT only) women. At equivalent doses, glyburide plasma concentrations were ~50% lower in pregnancy compared to non-pregnant women. Average glyburide umbilical cord to maternal plasma concentration ratio at the time of delivery was 0.7 ± 0.4. Insulin sensitivity was ~5-fold lower in women with GDM compared to healthy pregnancy. Despite comparable beta-cell responsivity index, average beta-cell function corrected for insulin resistance was >3.5-fold lower in women with glyburide-treated GDM than healthy pregnancy. Women with GDM that fail glyburide may benefit from alternate medication selection or dosage escalation, though fetal safety should be considered.Corresponding Author and Reprint Requests: Mary F. Hebert, Pharm.D., FCCP, University of Washington, Department of Pharmacy, 1959 NE Pacific St., H-375 Health Science Center, Box 357630, Seattle WA 98195-7630, Phone: 206-616-5016, Fax: 206-543-3835, Email: E-mail: mhebert@u.washington.edu. * Current address: Pfizer Global Research and Development, San Diego CA CONFLICT OF INTEREST/DISCLOSURE At the time of study conduct and analysis, the authors declare no conflict of interest. However, since completion of the study, Dr. Vicini's affiliation has become Pfizer Global Research and Development. NIH Public Access Author ManuscriptClin Pharmacol Ther. Author manuscript; available in PMC 2010 June 1. Published in final edited form as:Clin Pharmacol Ther. Gestational diabetes mellitus (GDM) complicates 5-12% of pregnancies and is associated with adverse pregnancy outcomes. Insulin has been the mainstay of pharmacotherapy for GDM. Glyburide's (GLY) advantages include easier route of administration and schedule as well as improved patient satisfaction and adherence. GLY's acceptance has been due to its comparable efficacy with insulin and limited transfer to the fetus.(1,2) However, the pharmacokinetics (PK) of GLY have not been studied in pregnancy and dosage strategies generally follow those used in non-pregnant patients with type 2 diabetes mellitus (T2DM). We hypothesized that the PK of GLY would be different during pregnancy, due to the expected changes in metabolism, protein binding, and body composition. In addition, the effects of GLY on the insulin sensitivity and secretion parameters have not been systematically studied. Our objectives were to compare GLY PK in women with GDM and non-pregnant T2DM, to measure fetal exposure to glyburide at delivery and to evaluate insulin sensitivity (SI), beta-cell responsivity index (Φ total ) and disposition index (DI) following a mixed meal tolerance test (MMTT) in women with GDM on GLY therapy, compared with gestational age-matched healthy pregnant ...
Surgical treatment is a safe and effective treatment for acromegaly and remains the first choice of treatment for most acromegalic patients. The results of this centre compare favourably with series from other centres. We have demonstrated improved results, both in terms of post operative growth hormone values and pituitary function tests with time and increasing neurosurgical experience. We conclude that outcome for the surgical treatment for acromegaly is best achieved with one surgeon specialising in pituitary surgery. Improved operative outcome thus achieved has major cost implications and avoids the necessity for consideration of postoperative radiotherapy and the use of expensive growth hormone suppressing drugs in the postoperative period.
Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low-or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI).Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression.
Recent reports have linked severe lung injuries and deaths to the use of e-cigarettes and vaping products. Nevertheless, the causal relationship between exposure to vaping emissions and the observed health outcomes remains to be elucidated. Through chemical and toxicological characterization of vaping emission products, this study demonstrates that during vaping processes, changes in chemical composition of several commonly used vape juice diluents (also known as cutting agents) lead to the formation of toxic byproducts, including quinones, carbonyls, esters, and alkyl alcohols. The resulting vaping emission condensates cause inhibited cell proliferation and enhanced cytotoxicity in human airway epithelial cells. Notably, substantial formation of the duroquinone and durohydroquinone redox couple was observed in the vaping emissions from vitamin E acetate, which may be linked to acute oxidative stress and lung injuries reported by previous studies. These findings provide an improved molecular understanding and highlight the significant role of toxic byproducts in vapingassociated health effects.
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