Pregnancy at high altitude in the Andes leads to increased total vessel density in healthy newborns.

The developing human fetus is able to cope with the physiological reduction in oxygen supply occurring in utero. However, it is not known if microvascularization of the fetus is augmented when pregnancy occurs at high altitude. Fifty-three healthy term newborns in Puno, Peru (3,840 m) were compared with sea-level controls. Pre- and postductal arterial oxygen saturation (SpO2) was determined. Cerebral and calf muscle regional tissue oxygenation was measured using near infrared spectroscopy (NIRS). Skin microcirculation was noninvasively measured using incident dark field imaging. Pre- and postductal SpO2 in Peruvian babies was 88.1 and 88.4%, respectively, which was 10.4 and 9.7% lower than in newborns at sea level (P < 0.001). Cerebral and regional oxygen saturation was significantly lower in the Peruvian newborns (cerebral: 71.0 vs. 74.9%; regional: 68.5 vs. 76.0%, P < 0.001). Transcutaneously measured total vessel density in the Peruvian newborns was 14% higher than that in the newborns born at sea level (29.7 vs. 26.0 mm/mm(2); P ≤ 0.001). This study demonstrates that microvascular vessel density in neonates born to mothers living at high altitude is higher than that in neonates born at sea level.

High-Sensitivity Troponin T and N-Terminal Pro-Brain Natriuretic Peptide in Prediction of Outcome in Congenital Diaphragmatic Hernia: Results from a Multicenter, Randomized Controlled Trial.

UNLABELLED: Biomarkers may be helpful in prediction of outcomes of infants with congenital diaphragmatic hernia. The predictive value of high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide was investigated in 128 infants with congenital diaphragmatic hernia. After correction for multiple testing, those biomarkers did not predict severe pulmonary hypertension, death, need of extracorporeal membrane oxygenation, or bronchopulmonary dysplasia. TRIAL REGISTRATION: Netherlands Trial Registry: 1310.

A specific adenylyl cyclase inhibitor (DDA) and a cyclic AMP-dependent protein kinase inhibitor (H-89) block the action of equine growth hormone on in vitro maturation of equine oocytes.

The objectives of this study were firstly to determine whether the stimulatory function of equine growth hormone (eGH) on equine oocyte maturation in vitro is mediated via cyclic adenosine monophosphate (cAMP); and secondly if the addition of eGH in vitro influences oocyte nuclear maturation and if this effect is removed when GH inhibitors are added to the culture. Cumulus-oocyte complexes (COCs) were recovered from follicles <25 mm in diameter and randomly allocated as follows: (i) control (no additives); and (ii) 400 ng/ml of eGH. A specific inhibitor against cyclic AMP-dependent protein kinase (H-89; 10-9, 10-11 or 10-15 M concentration) and a specific adenylate cyclase inhibitor, 2',3'-dideoxyadenosine (DDA; 10-8, 10-10 or 10-14 M concentration) were used to observe whether they could block the eGH effect. After 30 h of in vitro maturation at 38.5°C with 5% CO2 in air, oocytes were stained with 10 µg/ml of Hoechst to evaluate nuclear status. More mature oocytes (P < 0.05) were detected when COCs were incubated with eGH (29 of 84; 34.5%) than in the control group (18 of 82; 21.9%). The H-89 inhibitor used at a concentration of 10-9 M (4 of 29; 13.8%) decreased (P < 0.05) the number of oocytes reaching nuclear maturation when compared with eGH (11 of 29; 38%). The DDA inhibitor at a concentration of 10-8 M (2 of 27; 7.4%) also reduced (P < 0.05) the number of oocytes reaching maturity when compared with the eGH group (9 of 30; 30%). Results from the present study show that H-89 and DDA can be used in vitro to block the eGH effect on equine oocyte maturation.

Selection of developmentally competent immature equine oocytes with brilliant cresyl blue stain prior to in vitro maturation with equine growth hormone.

Immature oocytes synthesize a variety of proteins that include the enzyme glucose-6-phosphate dehydrogenase (G6PDH). Brilliant cresyl blue (BCB) is a vital blue dye that assesses intracellular activity of G6PDH, an indirect measure of oocyte maturation. The objective was to evaluate the BCB test as a criterion to assess developmental competence of equine oocytes and to determine if equine growth hormone (eGH) enhanced in vitro maturation (IVM) of equine oocyte. Cumulus-oocytes complexes (COCs) were recovered by aspirating follicles <30 mm in diameter from abattoir-derived ovaries and were evaluated morphologically. Thereafter, COCs were exposed to BCB (26 µM) for 90 min at 39°C and selected based on the colour of their cytoplasm (BCB positive/BCB+ or BCB negative/BCB-). The COCs were allocated as follows: (a) IVM medium; (b) eGH group; (c) BCB-/IVM; (d) BCB+/IVM; (e) BCB-/eGH; and (f) BCB+/eGH. Then, COCs were cultured in vitro for 30 h, at 39°C in a 5%CO2 humidified air atmosphere. Cumulus-free oocytes were incubated in 10 µg/ml of bis-benzamide for 20 min at 39°C and nuclear maturation was evaluated with epifluorescence microscopy. Of the 39 COCs selected morphologically and subjected to BCB staining, 18/39 (46.2%) were classified as BCB+ and 21/39 (53.8%) as BCB- (P > 0.05). Maturation was not affected significantly by BCB classification, but the maturation rate was higher for oocytes that had been exposed to exogenous eGH versus controls (16/28, 57.1% versus 8/26, 30.8%, P < 0.05). In the present study, the BCB test was not useful for predicting competent equine oocytes prior to IVM. However, eGH enhanced equine oocyte maturation in vitro.

The effect of growth hormone (GH) and insulin-like growth factor-I (IGF-I) on in vitro maturation of equine oocytes.

The objective of this study was to test the hypothesis that equine growth hormone (eGH), in combination with insulin growth factor-I (IGF-I), influences positively in vitro nuclear and cytoplasmic maturation of equine oocytes. Cumulus-oocyte complexes were recovered from follicles that were < 25 mm in diameter, characterized by morphology and were allocated randomly as follow: (a) control (no additives); (b) 400 ng/ml eGH; (c) 200 ng/ml IGF-I; (d) eGH + IGF-I; and (e) eGH + IGF-I + 400 ng/ml anti-IGF-I antibody. Oocytes were matured for 30 h at 38.5°C in air with 5% CO2 and then stained with 10 µg/ml propidium iodide (PI) to evaluate nuclear status and 10 µg/ml Lens culinaris agglutinin-fluorescein complex (FITC-LCA) to assess cortical granule migration by confocal microscopy. The proportion of immature oocytes that developed to the metaphase II (MII) stage in the eGH + IGF-I group (15 of 45) was greater than in the groups that were treated only with IGF-I (7 of 36, p = 0.03). Oocytes that reached MII in the control group (20 of 56; 35.7%) showed a tendency to be different when compared with eGH + IGF-I group (15 of 45; 33.3%, p = 0.08). The treated group that contained anti-IGF-I (15 of 33; 45.4%) decreased the number of oocytes reaching any stage of development when compared with eGH (47 of 72; 65.3%) and eGH + IGF-I (33 of 45; 73.3%) groups (p = 0.05) when data from MI and MII were combined. We concluded that the addition of eGH to in vitro maturation (IVM) medium influenced the in vitro nuclear and cytoplasmic maturation of equine oocytes. The use of GH and IGF-I in vitro may represent a potential alternative for IVM of equine oocytes.

Sudden infant death syndrome in Washington State: why are Native American infants at greater risk than white infants?

Washington State reports one of the highest rates of sudden infant death syndrome (SIDS) in the United States; within the state, Native Americans have the highest rate of any racial group. To explore this apparent genetic predisposition, we conducted a population-based retrospective cohort study. Using the state's linked birth and death certificate file for 1984 to 1988, we compared infants whose mothers were coded as "American Indian" with infants whose mothers were coded as "white." Native American infants were more than three times more likely than white infants to die of SIDS (crude relative risk = 3.25; 95% confidence interval = 2.41 to 4.38). However, this elevated risk diminished after adjustment for differences between Native American and white mothers in age, marital status, parity, and smoking status during pregnancy (adjusted relative risk = 1.82; 95% confidence interval = 1.28 to 2.58). The high SIDS rate of Washington's Native Americans appears to be due to the high prevalence of SIDS risk factors among Native American mothers, rather than to a genetic predisposition in the infants. Because many of these maternal factors are related to socioeconomic status, it is likely that programs to improve the overall health of Native Americans might lessen both the impact of SIDS and that of other causes of infant morbidity and death.

Screening practices for cervical and breast cancer in Costa Rica.

Cervical cancer and breast cancer are leading causes of cancer-related morbidity and mortality in Costa Rica. This article reports results of an evaluation of cervical and breast cancer screening practices among Costa Rican women 25 to 58 years old that was based on a nationwide 1984-1985 survey. The evaluation showed that while Pap smears were widely used to screen for cervical cancer, many women did not have their first cervical smear or gynecologic examination until age 30, and that cervical cancer screening was less common among certain high-risk groups, including women with multiple sexual partners and those with high parity. Less than half the women surveyed reported having had a breast examination by a health care provider. Utilization of both cervical cancer and breast cancer screening examinations could be increased by targeting inadequately screened high-risk women through the existing health care system.

Cervical cancer risk and use of depot-medroxyprogesterone acetate in Costa Rica.

The relationship between cervical cancer and the use of depot-medroxyprogesterone acetate (DMPA) was examined in a nationwide case-control study in Costa Rica. Cases were women ages 25-58 years of age with invasive squamous cell cancer (N = 149) or carcinoma in situ (CIS, N = 415) reported by the National Tumor Registry during 1982-84. Controls (N = 764) were randomly selected during a nationwide household survey. Using logistic regression, we adjusted for known risk factors for cervical cancer. DMPA use was associated with a risk of CIS of 1.1 (95% confidence interval 0.6-1.8) and a risk of invasive cancer of 1.4 (95% confidence interval 0.6-3.1). The slightly elevated risks observed may be the result of chance or a detection bias. One limitation of this study is that few women had used DMPA for longer than two years.

PIP: A nationwide case-control study was conducted in Costa Rica in 1984-85 to examine the association between depot-medroxyprogesterone acetate (DMPA) and cervical cancer. Cases, restricted to women 25-58 years of age at the time of diagnosis, were women with invasive squamous cell cancer (n = 149) or carcinoma in situ (CIS, n=415) reported by the National Tumor Registry during 1982-84. The 764 controls were randomly selected during a nationwide household survey. On average, the CIS cases were younger than controls; the invasive cases were older than controls. Both case groups were more likely than controls to be of low socioeconomic status, to have become sexually active at a young age, to report a history of a sexually transmitted disease or pelvic inflammatory disease, and to report having 3 or more partners in their lifetime. Ever users of DMPA had a risk of CIS of 1.1 when compared with never users. Women who 1st used DMPA before age 30 had a CIS risk of 0.6 whereas users who began use after age 39 had a risk of 2.0. Both of these risk estimates were based on small numbers of users. Ever users of DMPA had a risk of invasive cancer of 1.4 when compared with never users, but all estimates for invasive cancer were based on only 10 cases who reported use of DMPA. Few of the women had used DMPA for longer than 2 years.

Oral contraceptives and cervical cancer risk in Costa Rica. Detection bias or causal association?

To examine the relationship between cervical cancer and oral contraceptive (OC) use, we analyzed data from a population-based, case-control study in Costa Rica. Women aged 25 to 58 years in whom cervical cancer was diagnosed and reported to the National Tumor Registry were examined as two separate case groups: invasive cervical cancer and carcinoma in situ (CIS). Controls were women aged 25 to 58 years identified through a national survey. Women who had used OCs had no increased risk of invasive cervical cancer compared with women who had never used OCs (relative risk, 0.8; 95% confidence interval, 0.5 to 1.3). Women who had used OCs had an increased risk of CIS compared with those who had never used OCs (relative risk, 1.6; 95% confidence interval, 1.2 to 2.2). However, further analyses indicated that this increased risk was confined to those who had recently used OCs. Also, the risk of CIS was not elevated in subgroups in which a history of cervical smears was not strongly linked to OC use. The elevated risk of CIS among OC users may therefore reflect a bias caused by enhanced detection of disease rather than a causal association.