In-hospital Neonatal Mortality and the Role of Consanguinity

Background: Consanguinity which increases the risk of genetic disorders has been implicated at times in infant mortality. The aim of this study was to determine the association between consanguinity and in-hospital mortality in newborns. Methods: Data was collected prospectively on all births from 26 hospitals in Lebanon from January 2004 to December 2008 and admitted to the National Collaborative Perinatal Neonatal Network. Secondary analysis was done on 65,402 singletons, after exclusion of stillbirths, infants of multiple gestation and infants of second cousin progeny. Results: In-hospital mortality was 6.7 per 1000 live births (439/65,402). The rate of first cousin marriage was 9.9%. Consanguinity was significantly associated with in-hospital mortality (odds ratio 2.4; 95% confidence interval (CI): 1.8, 3.1); consanguinity remained a significant predictor of mortality (odds ratio 1.8 [95% CI: 1.2, 2.9]) after adjusting for maternal age and education, crowding index, history of abortion, prenatal care, mode of delivery, gender, birthweight and apgar score at 5 minutes. Conclusions: This association of consanguinity with in-hospital mortality points to potential genetic factors leading to this increased risk. Designing public health interventions, including raising the awareness and taking into consideration such risks in neonatal mortality studies are indicated.     

Effects of LH-RH and des-Gly10[D-Ala6]LH-RH-ethylamide on plasma gonadotropin levels and oocyte maturation in adult female coho salmon (Oncorhynchus kisutch)

Plasma gonadotropin (GtH) levels and state of oocyte development were determined in adult female coho salmon following single intraperitoneal injections of LH-RH or its superactive analog des-Gly10[D-Ala6]LH-RH-ethylamide (LH-RHA DAla6). The peptides injected at dosages of 1.0 or 0.2 mg LH-RH and 0.2 or 0.02 mg LH-RHA DAla6/kg bw elevated plasma GtH by 1.5 hr postinjection. The response to the analog was of longer duration. Plasma GtH levels returned to basal levels 24 hr following LH-RH injection while elevated plasma GtH levels were maintained for at least 96 hr in response to the analog. Only those fish injected with LH-RHA DAla6 showed an accelerated rate of germinal vesicle breakdown (GVBD). Based on their relative effects on GVBD, LH-RHA DAla6 has at least 50 times the biological potency of LH-RH in adult female coho salmon.     

A preliminary investigation of the effect of bovine growth hormone on growth and muscle composition of coho salmon (Oncorhynchus kisutch).

Groups of yearling coho salmon (Oncorhynchus kisutch) were acclimated to 10° well water and 12 hr photoperiod. Excess ration (Oregon Moist Pellet) was presented daily. Two doses, namely, 10 and 100 μg bovine growth hormone (bGH)/g/body wt/wk were administered by intraperitoneal injection (3×/wk) or by pellet implantation (1×/2 wk). Control fish received either alkaline saline or a cholesterol pellet. Treatment was continued for 8 wk (phase I) and the fish were then observed for a further 6 wk (phase II). In phase I, groups of fish given hormone (bGH fish) grew significantly faster (1.3–1.6% wt/day) than control fish (0.6–0.8%/day). Mean weights for bGH fish at 8 wk were 40–66% higher than those for respective control fish. Doses of 10 and 100 μg bGH/g/wk were equally potent in enhancing growth. Method of hormone administration did not significantly influence the growth of bGH fish. In phase II, bGH fish growth rates were lower (0.8–1.2%/day) than in phase I and approached those of control fish (0.9%/day). bGH fish became progressively leaner in phase I than control fish. This trend was stopped and reversed in phase II. At 8 wk bGH fish had significantly higher percentages of water and lower percentages of protein in their flesh than in control fish. No differences were noted between bGH and control fish in the histological structure of the thyroids and gonads.     

Rare steroid receptor-negative basal-like tumorigenic cells in luminal subtype human breast cancer xenografts

There are two major subtypes of human breast cancers: the luminal, estrogen, and progesterone receptor-positive, cytokeratin 18-positive (ER(+)PR(+)CK18(+)) subtype, and the basal ER(-)PR(-)CK18(-)CK5(+) subtype. Tumor-initiating cells (CD44(+)) have been described for human breast cancers; whether these are common to the two subtypes is unknown. We have identified a rare population of cells that are both CD44(+) and ER(-)PR(-)CK5(+) in luminal-like ER(+)PR(+) T47D human breast tumor xenografts. The tumor-isolated CD44(+) cell fraction was highly enriched for clonogenic (in vitro culture) and tumorigenic (in vivo reimplantation) cells compared with the CD44(-) cell fraction. Rare ER(-)PR(-)CK5(+) cells were present within CD44(+)-derived colonies. Tumor-isolated cells placed in minimal media also contained rare ER(-)PR(-)CK5(+) cells at early time points (<10 cells); however, this population did not expand with increasing colony size. The number of ER(+)PR(+)CK5(-) cells, conversely, increased linearly with colony growth. Similary, tumors originating in vivo from CD44(+) cells contained a rare static ER(-)PR(-)CK5(+) population, an intermediate ER(-)PR(-)CK5(-) population, and an expanding ER(+)PR(+)CK5(-) population. Putative ER(+)PR(+)CK5(+) transitional cells could be seen only in colonies or tumors treated with a progestin. We propose that luminal ER(+)PR(+) breast tumors contain a minor ER(-)PR(-)CK5(+) population that has the capacity to generate the majority of ER(+)PR(+)CK18(+)CK5(-) cells. Luminal breast cancers are treated with endocrine therapies that target ER. The rare ER(-)PR(-)CK5(+) progenitor cells would escape such treatments and survive to repopulate the tumor.     

Factors Associated With Microalbuminuria in 7,549 Children and Adolescents With Type 1 Diabetes in the T1D Exchange Clinic Registry

OBJECTIVE

To examine factors associated with clinical microalbuminuria (MA) diagnosis in children and adolescents in the T1D Exchange clinic registry.

RESEARCH DESIGN AND METHODS

T1D Exchange participants <20 years of age with type 1 diabetes ≥1 year and urinary albumin-to-creatinine ratio (ACR) measured within the prior 2 years were included in the analysis. MA diagnosis required all of the following: 1) a clinical diagnosis of sustained MA or macroalbuminuria, 2) confirmation of MA diagnosis by either the most recent ACR being ≥30 mg/g or current treatment with an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB), and 3) no known cause for nephropathy other than diabetes. Logistic regression was used to assess factors associated with MA.

RESULTS

MA was present in 329 of 7,549 (4.4%) participants, with a higher frequency associated with longer diabetes duration, higher mean glycosylated hemoglobin (HbA_1c) level, older age, female sex, higher diastolic blood pressure (BP), and lower BMI (P ≤ 0.01 for each in multivariate analysis). Older age was most strongly associated with MA among participants with HbA_1c ≥9.5% (≥80 mmol/mol). MA was uncommon (<2%) among participants with HbA_1c <7.5% (<58 mmol/mol). Of those with MA, only 36% were receiving ACEI/ARB treatment.

CONCLUSIONS

Our results emphasize the importance of good glycemic and BP control, particularly as diabetes duration increases, in order to reduce the risk of nephropathy. Since age and diabetes duration are important nonmodifiable factors associated with MA, the importance of routine screening is underscored to ensure early diagnosis and timely treatment of MA.Elevated urinary albumin excretion is an early sign of diabetic kidney disease (DKD). The American Diabetes Association (ADA) recommends screening for microalbuminuria (MA) annually in people with type 1 diabetes after 10 years of age and 5 years of diabetes duration, with a diagnosis of MA requiring two of three tests to be abnormal (1). Early diagnosis of MA is important because effective treatments exist to limit the progression of DKD (1). However, although reduced rates of MA have been reported over the past few decades in some (2–4) but not all (5,6) studies, it has been suggested that the development of proteinuria has not been prevented but, rather, has been delayed by ∼10 years and that further improvements in care are needed (7).Limited data exist on the frequency of a clinical diagnosis of MA in the pediatric population with type 1 diabetes in the U.S. Our aim was to use the data from the T1D Exchange clinic registry to assess factors associated with MA in 7,549 children and adolescents with type 1 diabetes.