HIGH ALTITUDE PULMONARY OEDEMA - AN EXPERIENCE IN EASTERN HIMALAYA.
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ABSTRACT:
SUBMITTER: Virmani SK
PROVIDER: S-EPMC5530972 | biostudies-other | 1997 Jul
REPOSITORIES: biostudies-other
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Project description:High-altitude cerebral oedema (HACO) is the most fatal high-altitude illness seen by rural physicians practising in high-altitude areas. HACO presents clinically with cerebellar ataxia, features of raised intracranial pressure (ICP) and coma. Early identification is important as delay in diagnosis can be fatal. We present two cases of HACO presenting with focal deficits mimicking stroke. The first patient presented with left-sided hemiplegia associated with the rapid deterioration in the sensorium. Neuroimaging revealed features suggestive of vasogenic oedema. The second patient presented with monoplegia of the lower limb. Neuroimaging revealed perfusion deficit in anterior cerebral artery territory. Both patients were managed with dexamethasone and they improved dramatically. Clinical picture and neuroimaging closely resembled acute ischaemic stroke in both cases. Thrombolysis in these patients would have been disastrous. Recent travel to high altitude, young age, absence of atherosclerotic risk factors and features of raised ICP concomitantly directed the diagnosis to HACO.
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Project description:A nested case-control study was undertaken on a cohort of soldiers inducted into high altitude area (11000 to 16000 feet) of Western Himalayas, with the objectives of studying the incidence of high altitude pulmonary oedema (HAPO) and its association with physical exertion and certain other predetermined risk factors. The study indicated that the cumulative incidence of HAPO was 1.42 per 1000 inductions. The association with moderate/strenuous physical exertion within 24 hours of entry into high altitude was significant (Odds ratio (OR) = 3.19; 95% confidence limits (CL) = 1.23 to 8.15); however, this association was not significant for the period 24 to 48 hours or > 48 hours. Physical exertion during first 24 hours was also significantly associated with severity of disease (OR = 14.67, 95% CL = 3.61 to 64.04), but not after 24 hours. Previous history of "high altitude sickness" was also significantly associated with HAPO (OR = 2.74, 95% CL = 1.12 to 6.77). Physical exertion during first 24 hours was found to carry an attributable risk of 2.56 per 1000 inductions and an etiologic fraction of 17.8%. No significant association of HAPO was observed with age, type of inductee (fresh/reinductee), native place, alcohol consumption and smoking.
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Project description:AimHigh-altitude pulmonary oedema (HAPE) is a non-cardiogenic pulmonary oedema that can occur during rapid ascent to a high-altitude environment. Classically, HAPE has been described as a condition resulting from a combination of pulmonary vasoconstriction and hypertension. Inflammation has been described as important in HAPE, although as a side effect of pulmonary oedema rather than as a causative factor. In this study, we aim to understand the role of hypoxic response in myeloid cells and its involvement in pathogenesis of HAPE.MethodsWe have generated a conditional deletion in mice of the von Hippel-Lindau factor (VHL) in myeloid cells to determine the effect of a deregulated hypoxic response in pulmonary oedema.ResultsThe deletion of VHL in pulmonary myeloid cells gave rise to pulmonary oedema, increased pulmonary vascular permeability and reduced performance during exertion. These changes were accompanied by reduced stroke volume in the left ventricle.ConclusionIn this model, we show that a deregulated myeloid cell hypoxic response can trigger some of the most important symptoms of HAPE, and thus mice with a deletion of VHL in the myeloid lineage can function as a model of HAPE.
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Project description:High altitude pulmonary oedema (HAPE) severely affects non-acclimatized individuals and is characterized by alveolar flooding with protein-rich oedema as a consequence of blood-gas barrier disruption. Limited choice for prophylactic treatment warrants effective therapy against HAPE. Keratinocyte growth factor-2 (KGF-2) has shown efficiency in preventing alveolar epithelial cell DNA damages in vitro. In the current study, the effects of KGF-2 intratracheal instillation on mortality, lung liquid balance and lung histology were evaluated in our previously developed rat model of HAPE. We found that pre-treatment with KGF-2 (5 mg/kg) significantly decreased mortality, improved oxygenation and reduced lung wet-to-dry weight ratio by preventing alveolar-capillary barrier disruption demonstrated by histological examination and increasing alveolar fluid clearance up to 150%. In addition, KGF-2 significantly inhibited decrease of transendothelial permeability after exposure to hypoxia, accompanied by a 10-fold increase of Akt activity and inhibited apoptosis in human pulmonary microvascular endothelial cells, demonstrating attenuated endothelial apoptosis might contribute to reduction of endothelial permeability. These results showed the efficacy of KGF-2 on inhibition of endothelial cell apoptosis, preservation of alveolar-capillary barrier integrity and promotion of pulmonary oedema absorption in HAPE. Thus, KGF-2 may represent a potential drug candidate for the prevention of HAPE.
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Project description:The Central Asian Kyrgyz highland population provides a unique opportunity to address genetic diversity and understand the genetic mechanisms underlying hypoxia-induced high altitude pulmonary hypertension (HAPH). While a significant fraction of the population is unaffected, there are susceptible individuals who display HAPH in the absence of any lung, cardiac or hematologic disease. We report herein the analysis of the whole genome sequencing of healthy individuals compared with HAPH patients and other controls.
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Project description:Data Access Committee EGAC00001000994
| EGAC00001000994 | EGA
Project description:The transition from hunting to herding transformed the cold, arid steppes of Mongolia and Eastern Eurasia into a key social and economic center of the ancient world, but a fragmentary archaeological record limits our understanding of the subsistence base for early pastoral societies in this key region. Organic material preserved in high mountain ice provides rare snapshots into the use of alpine and high altitude zones, which played a central role in the emergence of East Asian pastoralism. Here, we present the results of the first archaeological survey of melting ice margins in the Altai Mountains of western Mongolia, revealing a near-continuous record of more than 3500 years of human activity. Osteology, radiocarbon dating, and collagen fingerprinting analysis of wooden projectiles, animal bone, and other artifacts indicate that big-game hunting and exploitation of alpine ice played a significant role during the emergence of mobile pastoralism in the Altai, and remained a core element of pastoral adaptation into the modern era. Extensive ice melting and loss of wildlife in the study area over recent decades, driven by a warming climate, poaching, and poorly regulated hunting, presents an urgent threat to the future viability of herding lifeways and the archaeological record of hunting in montane zones.
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Project description:BACKGROUND:Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers. METHODS/DESIGN:D4H is a double-blind placebo-controlled randomised trial assessing the effect of dexamethasone on hypoxia-induced cerebral oedema. In total, 20 volunteers were randomised in pairs to receive either 8.25?mg dexamethasone or normal saline placebo intravenously after 8?h of hypoxia with an FiO2 of 12%. Serial MRI images of the brain and spinal cord were obtained at hours 0, 7, 11, 22 and 26 of the study along with serum and urinary markers to correlate with the severity of cerebral oedema and the effect of the intervention. DISCUSSION:MRI has been used to identify changes in cerebral vasculature in the development of AMS and HACE. Dexamethasone is effective at reducing the symptoms of AMS; however, the mechanism of this effect is unknown. If this study demonstrates a clear objective benefit of dexamethasone in this setting, future studies may be able to demonstrate that dexamethasone is an effective therapy for oedema associated with brain and spinal cord ischaemia beyond AMS. TRIAL REGISTRATION:Clinicaltrials.gov, NCT03341676 . Registered on 14 November 2017.
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Project description:The present research has been performed to analyze the chemical behavior of rainwater of the Shaune Garang catchment (32.19° N, 78.20° E) in the Baspa basin, located at a high elevation (4221 m above mean sea level) in the Himachal Himalaya, India. During the study period, sixteen rainwater samples were collected from the Shaune Garang catchment at five different sites. The volume-weighted mean (VWM) pH value of rainwater ranged between 4.59 and 6.73, with an average value of 5.47 ± 0.69, indicating the alkaline nature of rainfall. The total ionic strength in the rainwater ranged from 113.4 to 263.3 µeq/l with an average value of 169.1 ± 40.4 µeq/l. The major dominant cations were Ca2+ (43.10%) and Na+ (31.97%) and anions were Cl- (37.68%), SO42- (28.71%) and NO3- (23.85%) in rainwater. The ionic ratios were calculated among all the ions. The fraction of (NO3- +Cl-) with SO42- was measured as 2.3, which specifies sour faces of rainwater due to HNO3, H2SO4, and HCl. A multivariate statistical assessment of rainwater chemistry through Principal Component Analysis (PCA) shows the significance of four factors controlling 78.37% of the total variance, including four-component (PC1 explained 27.89%, PC2 explained 24.98%, PC3 explained 14.64%, PC4 explained 10.85%). However, the individual contribution of Factor 1(PC1) explains 27.89% of the total variance (78.37%) and displays a strong optimistic loading for Ca2+ and Cl-. Further, high loading of Ca2+ and NO3- and moderate loading of SO42- signify the contribution of burning fossil fuel and soil dust. Anthropogenic and natural pollutants influence the composition of rainwater in the pristine Himalayas due to local and long-distance transportation. The study area receives precipitation from the West and North-West, transporting dust and fossil fuel emissions from the Thar Desert and Northwestern countries.
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