We show that a vascular endothelial growth factor (VEGF) pathway controls embryonic migrations of blood cells (hemocytes) in Drosophila. The VEGF receptor homolog is expressed in hemocytes, and three VEGF homologs are expressed along hemocyte migration routes. A receptor mutation arrests progression of blood cell movement. Mutations in Vegf17E or Vegf27Cb have no effect, but simultaneous inactivation of all three Vegf genes phenocopied the receptor mutant, and ectopic expression of Vegf27Cb redirected migration. Genetic experiments indicate that the VEGF pathway functions independently of pathways governing hemocyte homing on apoptotic cells. The results suggest that the Drosophila VEGF pathway guides developmental migrations of blood cells, and we speculate that the ancestral function of VEGF pathways was to guide blood cell movement.
Infant mortality and stillbirth rates in Bolivia are high and birth weights are low compared with other South American countries. Most Bolivians live at altitudes of 2500 m or higher. We sought to determine the impact of high altitude on the frequency of preeclampsia, gestational hypertension, and other pregnancy-related complications in Bolivia. We then asked whether increased preeclampsia and gestational hypertension at high altitude contributed to low birth weight and increased stillbirths. We performed a retrospective cohort study of women receiving prenatal care at low (300 m, Santa Cruz, n ϭ 813) and high altitude (3600 m, La Paz, n ϭ 1607) in Bolivia from 1996 to 1999. Compared with babies born at low altitude, high-altitude babies weighed less (3084 Ϯ 12 g versus 3366 Ϯ 18 g, p Ͻ 0.01) and had a greater occurrence of intrauterine growth restriction [16.8%; 95% confidence interval (CI): 14.9 -18.6 versus 5.9%; 95% CI: 4.2-7.5; p Ͻ 0.01]. Preeclampsia and gestational hypertension were 1.7 times (95% CI: 1.3-2.3) more frequent at high altitude and 2.2 times (95% CI: 1.4 -3.5) more frequent among primiparous women. Both high altitude and hypertensive complications independently reduced birth weight. All maternal, fetal, and neonatal complications surveyed were more frequent at high than low altitude, including fetal distress (odds ratio, 7.3; 95% CI: 3.9 -13.6) and newborn respiratory distress (odds ratio, 7.3; 95% CI: 3.9 -13.6; p Ͻ 0.01). Hypertensive complications of pregnancy raised the risk of stillbirth at high (odds ratio, 6.0; 95% CI: 2.2-16.2) but not at low altitude (odds ratio, 1.9; 95% CI: 0.2-17.5). These findings suggest that high altitude is an important factor worsening intrauterine mortality and maternal and infant health in Bolivia. Abbreviations PE, preeclampsia GH, gestational hypertension IUGR, intrauterine growth restriction CNS, Caja Nacional de Salud (National Health Care Fund) BP, blood pressure IUM, intrauterine mortality SGA, small-for-gestational age 95% CI, 95% confidence intervals OR, odds ratio Bolivia's infant mortality is the highest in the Western Hemisphere, its maternal mortality second only to Haiti (1) and its intrauterine mortality the second highest of 19 South American countries (2). Some 75% of the Bolivian population and 140 million persons worldwide, including an appreciable fraction of the other Andean countries, reside at high altitude (Ͼ2500 m) (1, 3, 4). Within Bolivia, neonatal mortality rates rise progressively with increasing altitude, averaging 20 deaths per 1000 live births lower than 2500 m, 33 in the 2500 -3500 m region of the country, and 44 higher than 3500 m (4). Maternal mortality also rises with increasing altitude within Bolivia, averaging 110 deaths/100,000 live births at low altitude, 293 in the intermediate altitudes, and 602 in the high regions (5).A number of factors likely contribute to the altitude-related increase in infant and maternal mortality in Bolivia. A recent retrospective, stratified survey identified lack of schooling, living in a...
To provide guidance to clinicians about best preventive and therapeutic practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to prevention and management of each form of acute altitude illness that incorporate these recommendations. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2010 and subsequently updated as the WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness in 2014.
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