Return of fertility following discontinuation of an injectable contraceptive — Norethisterone oenanthate (NET EN) 200mg dose

The return of fertility following discontinuation of norethisterone oenanthate (NET EN) 200 mg injectable contraceptive after use for a minimum period of six months or more was studied in 69 women who discontinued the method for planning pregnancy. Former users of copper intra-uterine device (CuT 200) were enrolled as a control group. Another 161 women who had discontinued NET EN due to other reasons (e.g. amenorrhoea, excessive bleeding or personal reasons) were also studied for return of fertility after ensuring that they were not using any other method of contraception and were exposed to the risk of pregnancy. The subjects from both groups were followed for a period of one year. The cumulative conception rates at one year were 72.5 and 83.6 per 100 subjects for ex-NET EN and ex-CuT 200 users who had discontinued the method for planning pregnancy and this difference was not statistically significant (P > 0.05). The median time for conception for ex-NET EN users was 7.8 months as compared to 3.7 months in ex-CuT 200 users but the cumulative conception rates at the end of one year show that future return of fertility in NET EN users does not appear to be adversely affected.

In 51 subjects who had discontinued NET EN due to amenorrhoea, the return of fertility was predictably slower and less. The return of fertility in subjects who discontinued NET EN for other reasons (e.g. excessive bleeding and other personal reasons) was similar to ex-NET EN and ex-CuT 200 users.     

Evaluation of active and passive transport processes in corneas extracted from preserved rabbit eyes

In vitro transcorneal permeability studies are an important screening tool in drug development. The objective of this research is to examine the feasibility of using corneas isolated from preserved rabbit eyes as a model for permeability evaluation. Eyes from male New Zealand White rabbits were used immediately or were stored overnight in phosphate-buffered saline (PBS) or Hanks balanced salt solution (HBSS) over wet ice. Integrity of isolated corneas was evaluated by measuring the TEER and by determining the permeability of paracellular and transcellular markers. Active transport was assessed by measuring transcorneal permeability of selected amino acids. Esterase activity was estimated using p-nitrophenyl assay. In all cases, corneas from freshly enucleated eyes were compared to those isolated from the day-old preserved eyes. Transcellular and paracellular passive diffusion was not affected by the storage medium and observed to be similar in the fresh and preserved eye models. However, amino acid transporters demonstrated lower functional activity in corneas excised from eyes preserved in PBS. Moreover, preserved eyes displayed almost 1.5-fold lower esterase activity in the corneal tissue. Thus, corneas isolated from day-old eyes, preserved in HBSS, closely mimics freshly excised rabbit corneas in terms of both active and passive transport characteristics but possesses slightly reduced enzymatic activity. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1921–1930, 2010     

Biomarkers of inflammation predict both vascular and non-vascular mortality in older men.

AIMS: To compare the predictive value of inflammatory biomarkers and lipids for vascular and non-vascular mortality in older men. METHODS AND RESULTS: The relevance of inflammatory biomarkers and lipids for vascular and non-vascular mortality was assessed in a prospective study of 5360 men (mean age 77 years) followed for 7 years. Vascular mortality was positively associated with log C-reactive protein (lnCRP), fibrinogen and total/HDL-C (high-density lipoprotein cholesterol), and inversely associated with albumin [age adjusted hazard ratio (HR) per 2-SD higher usual level (approximately the difference between the top and the bottom thirds of the distribution): 2.09 for lnCRP; 1.70 for fibrinogen; 0.50 for albumin and 1.45 for total/HDL-C]. The associations with the inflammatory markers were attenuated after adjustment for established risk factors, including lipids [adjusted HRs: 1.86 (lnCRP); 1.44 (fibrinogen); 0.51 (albumin)], and further attenuated (and, for fibrinogen, no longer predictive) after adjustment for each other [fully adjusted HRs: 1.60 (lnCRP); 1.01 (fibrinogen); 0.61 (albumin)]. Higher CRP and lower albumin levels were also associated with significantly raised non-vascular mortality independently of other characteristics [fully adjusted HRs: 1.62 (lnCRP); 0.65 (albumin)]. CONCLUSION: In this cohort of older men, higher CRP and lower albumin levels strongly predicted both vascular and non-vascular mortality, independently of other characteristics.     

Acute kidney injury and its association with in-hospital mortality among children with acute infections

Background

We investigated prevalence of acute kidney injury (AKI) at hospitalization and its association with in-hospital mortality among Ugandan children hospitalized with common acute infections, and predictors of mortality among AKI children.

Methods

We enrolled 2,055 children hospitalized with primary diagnoses of acute gastroenteritis, malaria, or pneumonia. Serum creatinine, albumin, electrolytes, hemoglobin, and urine protein were obtained on admission. Participants were assessed for AKI based on serum creatinine levels. Demographic and clinical data were obtained using a primary care provider survey and medical chart review. Logistic regression was used to determine predictors of in-hospital mortality.

Results

A total of 278 (13.5 %) of children had AKI on admission; for 76.2 %, AKI was stage 2 (98/278) or stage 3 (114/278) defined as serum creatinine >2- or 3-fold above normal upper limit for age, respectively. AKI prevalence was particularly high in gastroenteritis (28.6 %) and underweight children (20.7 %). Twenty-five percent of children with AKI died during hospitalization, compared to 9.9 % with no AKI (adjusted odds ratio (aOR) 3.5 (95 % CI, 2.2–5.5)). In-hospital mortality risk did not differ by AKI stage. Predictors of in-hospital mortality among AKI children included primary diagnosis of pneumonia, aOR 4.5 (95 % CI, 1.8–11.2); proteinuria, aOR = 2.1 (95 % CI, 1.0–4.9) and positive human immunodeficiency virus (HIV) status, aOR 5.0 (95 % CI, 2.0–12.9).

Conclusions

Among children hospitalized with gastroenteritis, malaria, or pneumonia, AKI at admission was common and associated with high in-hospital mortality.