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New epilepsy seizure at high altitude without signs of acute mountain sickness or high altitude cerebral edema.

Neurological disturbances may be present at high altitude independently of high altitude cerebral edema. We report here the case of a patient who experienced for the first time generalized seizures after spending a night at an altitude of 5200 m, with no preceding symptoms of acute mountain sickness. An initial CT scan performed 12 hours after his loss of consciousness and an MRI scan performed 2 months later were normal. An EEG, obtained 2 months after the event, showed epileptiform discharges triggered by hyperventilation. The description of the clinical event obtained from the witness and the presence of a positive family history strongly support a high altitude-triggered new epileptic seizure. This report suggests that at high altitudes seizure risks in a seizure-prone person may be higher than for normal individuals.

Acute Disease↗

Accentuated hypoxemia at high altitude in subjects susceptible to high-altitude pulmonary edema.

To investigate the hypotheses that activated coagulation, catecholamine release, or arginine vasopressin release are involved in the pathogenesis of high-altitude pulmonary edema (HAPE), we measured these variables in seven subjects susceptible to HAPE and in nine control subjects at an altitude of 1,600 m, and after 6 and 12 h at a simulated altitude of 4,150 m. Each subject was studied twice, once after 3 days of placebo medication and once after 3 days of premedication with aspirin and dipyridamole. At high altitude, HAPE-susceptible subjects showed significantly exaggerated hypoxemia and a slightly higher end-tidal carbon dioxide partial pressure that did not account fully for the hypoxemia. Fibrinolytic activity was significantly accelerated in both groups at high altitude, whereas other coagulation measurements, catecholamines and arginine vasopressin levels, and pulmonary function tests were not significantly changed. Similar findings were obtained after both placebo and platelet-inhibitor premedication. The results indicate that none of the three hypothesized mechanisms, i.e., activated coagulation, excessive catecholamine release, or antidiuresis, would account for HAPE susceptibility. Instead, HAPE-susceptible subjects exhibited exaggerated hypoxemia associated with relative hypoventilation and a widened alveolar-arterial gas pressure difference.

Adolescent↗

High-altitude pulmonary edema at moderate altitude (< 2,400 m; 7,870 feet): a series of 52 patients.

STUDY OBJECTIVES: To describe a group of patients who acquired pulmonary edema at a moderate altitude of 1,400 to 2,400 m. DESIGN: Observational, retrospective chart review (1992-2000) of a series of 52 consecutive patients admitted for high-altitude pulmonary edema (HAPE) that occurred at 1,400 to 2,400 m. SETTING: Emergency department of a community hospital in the French Alps (altitude, 500 m). PATIENTS: Vacationing skiers who met criteria for altitude-related pulmonary edema, and in whom other causes (infectious, cardiogenic, neurogenic, and toxic) were excluded. MEASUREMENTS AND RESULTS: All patients presented with signs of pulmonary edema. Diagnoses of infectious, cardiogenic, neurogenic, or toxic edema were ruled out in each patient. All patients were hypoxemic and had radiographic signs of pulmonary edema. Virtually all patients (96%) had dyspnea, and most (77%) had moist rales. All patients were treated with supplemental oxygen (3 to 12 L/min), bed rest, moderate fluid restriction, and continuous positive airway pressure. All recovered fully and were discharged after 4 +/- 2 days (mean +/- SD). CONCLUSION: This study suggests that HAPE at moderate altitudes is more frequent than usually reported. Patients are likely to be young, vacationing men, with no history of prior disease. The disease has a favorable prognosis, and requires simple treatment and a short hospital stay.

Adolescent↗

The difference of mutation in the peroxisome proliferator activated receptor gamma2 gene among people at high altitudes and low altitudes in Bolivia.

Peroxisome proliferator activated receptor (PPAR) gamma is present in two isoforms generated by alternative splicing, PPAR gamma 1 and PPAR gamma 2. A Pro12Ala polymorphism in human PPAR gamma 2 moderately reduces its transcriptional activity, and thus PPAR gamma 2 is thought to be a promising candidate gene for several human disorders, including obesity and type 2 diabetes mellitus. In this report, we examined the polymorphism of the PPAR gamma 2 gene in people at high and low altitudes in Bolivia, and found a significant difference in the frequency of Ala carriers (Pro/Ala and Ala/Ala) between 153 native high-altitude Bolivian subjects (64.1%) and 288 low-altitude Bolivian subjects (37.9%). The frequency of this Ala allele in Bolivian subjects was fairly higher than that in other ethnic groups. As body mass index, however, was not associated with Pro12Ala polymorphism of the PPAR gamma 2 gene among either the high altitude Bolivians or low altitude Bolivians, Pro12Ala polymorphism of the gene has little relationship to obesity in Bolivians.

Altitude↗

Irregular nocturnal breathing patterns high altitude in subjects susceptible to high-altitude pulmonary edema (HAPE): a preliminary study.

We studied nocturnal breathing patterns and symptoms of acute mountain sickness (AMS) during trekking in the Japanese Alps (altitude: 2,760-2,920 m) for 4 d in five subjects susceptible to high-altitude pulmonary edema (HAPE-S-S) and five control volunteers. Breathing patterns were evaluated with the impedance plethysmograph, and symptoms of AMS were evaluated by the environmental symptoms questionnaire-III score for AMS of cerebral type (AMS-C score). In both groups, the percentage of time with periodic breathing significantly increased at high altitude and the percentage in controls was significantly higher than in HAPE-S-S on the second night. In four HAPE-S-S, other disordered breathing patterns, termed "irregular breathing," were observed frequently by night at high altitude. Irregular breathing patterns were characterized by irregularly repeated oscillatory or nonoscillatory clusters of breaths with augmented tidal volume, followed by expiratory pause, apnea, or hypoventilation of various durations. All controls did not show significant changes in AMS-C score, but four HAPE-S-S showed the increase in AMS-C score on the next morning after frequent irregular nocturnal breathing. There was significant correlation between the percentage of time with irregular nocturnal breathing and AMS-C score on the next morning. These results suggest that HAPE-S-S are prone to irregular nocturnal breathing patterns at high altitude, which is associated with the development of AMS, but it was not possible to determine whether these abnormal breathing patterns are a cause or an effect of AMS.

Adult↗

Autonomic responses of high-altitude natives during sojourn at plains and on return to altitude.

The study was conducted on 20 high-altitude natives (HAN-I) 19-32 years old, to evaluate the changes in autonomic responses during their 2-months sojourn on the plains, and on return to high altitude (HA). The autonomic indices measured were heart rate HR), blood pressure (BP), oral temperature (Tor), mean skin temperature (Tsk), respiratory rate (RR), Cold pressor response (CPR), HR-response to tilt at 70 degree, and alpha index (AI) of EEG (occipital). These indices were recorded periodically during the 2 months of their stay on the plains, and thereafter on return to altitude for a period of 1 month. For comparison, the same responses were studied on 10 lowlanders (LL) on the plains and on induction to HA along with HAN-I. The study was repeated at altitude, once on 10 HAN who had never been to the plains (HAN-II) and on 10 acclimatised lowlanders. The results suggest that the relative parasympathetic dominance observed in natives at HA showed a gradual decrease during their sojourn on the plains, probably due to the elevation in sympathetic activity. On return to high altitude, they showed further increase in sympathetic excitation, as observed in LL on acute induction, but the magnitude of this response was less in natives. However, they showed a trend to faster return of autonomic responses to their initial level compared to LL.

Adaptation, Physiological↗

Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude.

Individuals susceptible to high-altitude pulmonary oedema (HAPE) are characterised by an abnormal increase of pulmonary artery systolic pressure (PASP) in hypoxia and during normoxic exercise, reduced hypoxic ventilatory response, and smaller lung volume. In 37 mountaineers with well-documented altitude tolerance, it was investigated whether any combination of these noninvasive measurements, including exercise in hypoxia, could improve the identification of HAPE-susceptible subjects at low altitude. HAPE-susceptible subjects showed a significant higher increase of PASP during hypoxia at rest (48+/-10 mmHg) compared with controls (38+/-3 mmHg), as well as during normoxic exercise (57+/-14 versus 38+/-7 mmHg) and hypoxic exercise (69+/-13 versus 49+/-8 mmHg). PASP could not be assessed in three and eight subjects during normoxic or hypoxic exercise, respectively, due to insufficient Doppler profiles or systemic arterial hypertension. Sensitivity (77-94%) and specificity (76-93%) were not significantly different between the various testing conditions. Additional assessment of hypoxic ventilatory response and lung function parameters did not improve identification of HAPE-susceptible subjects in a multivariate analysis. Due to the greater number of missing values in pulmonary artery systolic pressure measurements during hypoxic exercise, it was concluded that pulmonary artery systolic pressure measurements at rest during hypoxia or exercise in normoxia are most feasible for the identification of high-altitude pulmonary oedema-susceptible subjects.

Altitude↗

Lactate dehydrogenase activity and insulin and lactate levels at an altitude below sea level (-350 m) compared to those at an altitude above sea level (620 m) after exercise.

This study was designed to investigate the effect of exercise at 350 m below sea level altitude (-350 m) on the serum levels of lactate dehydrogenase (LDH), insulin, and lactate. The study was carried out on ten trained adult males with mean age of 23.3 +/- 3.4 years following a 21-km noncompetitive run. Venous blood was withdrawn from the subjects before exercise and 5 min post exercise. For comparison purposes, a similar study was performed with the same subjects but at 620 m above sea level (+620 m). The results show a significant increase in LDH and lactate levels after exercise only at low altitude (-350 m). Serum insulin levels decreased significantly after exercise at both altitudes. These changes in serum levels of LDH, insulin, and lactate at different altitudes suggest that a type of metabolic adjustment is present that meets energy requirements during exercise.

Adult↗

Genetic polymorphisms in the Renin-Angiotensin system in high-altitude and low-altitude Native American populations.

Cardiovascular disease (CVD) is reportedly less common in high-altitude native populations than in lowlanders. To some extent, this is due to cultural and demographic factors; however, increased cardiovascular efficiency contributing to hypoxia adaptation may also be involved. Numerous genetic variants have been associated with cardiovascular health. If the decreased incidence of CVD in modern high-altitude populations reflects selective pressures having favoured the transmission of these alleles in their antecedents, it would be expected that these alleles would be more common in highlanders than in lowlanders. We tested this hypothesis by determining the allele frequencies of five polymorphic loci in genes encoding components of the renin-angiotensin system (RAS) that have alleles associated with hypertension and cardiovascular disease in a high-altitude native Andean population, Quechua from the Peruvian altiplano, and in a lowland Amerindian population, Maya from the Yucatan peninsula. The polymorphisms examined were 1) the insertion/deletion polymorphism in intron 16 of the angiotensin converting enzyme (ACE) gene; 2) the A/G2350 transition (ACE-8) in intron 17 of the ACE gene; 3) the A/C1166 transversion in the 3' untranslated region of the angiotensin II receptor (type 1) gene (AGTR1); 4) the G/AI9-83 transition in intron 8 of the renin gene (REN); and 5) the T/C704 (Met235Thr) transition mutation in angiotensinogen (AGT). There was no evidence for an over-representation of the RAS alleles associated with cardiovascular fitness in the high-altitude Amerindian population when compared to the lowland Amerindian population.

Altitude↗

Fertility of Nepalese Sherpas at moderate altitudes: comparison with high-altitude data.

Data are reported on ages at menarche, first marriage and first childbirth and on completed fertility, in Sherpa populations of Nepal at moderate altitude (2200-2600 metres). Comparison of these data with similar data from two high-altitude surveys (Weitz et al. 1978, Gupta, 1978) indicates that cultural factors, examined in detail by Weitz et al. (1978), are probably insufficient to explain the lower completed fertility in high-altitude Sherpas. It is concluded that this lower fertility is mostly attributable to lower fecundity, and partly to the later mean age at first childbirth and the higher proportion of celibate nuns in high-altitude Sherpas.

Adolescent↗

Austrian Moderate Altitude Study (AMAS 2000): erythropoietic activity and Hb-O(2) affinity during a 3-week hiking holiday at moderate altitude in persons with metabolic syndrome.

Moderate altitude hypoxia (1500 to 2500 m) is known to stimulate erythropoiesis and to improve oxygen transport to tissue by a reduction of Hb-O(2) affinity. Whether this adaptation also occurs in tourists with metabolic syndrome has not yet been investigated sufficiently. Thus, we performed a prospective field study to measure erythropoietic parameters and oxygen transport properties in 24 male volunteers with metabolic syndrome during a 3- week holiday program at 1700 m consisting of four guided, individually adapted hiking tours per week. The following examinations were performed: baseline investigations at 500 m (T1); examinations at moderate altitude on day 1 (T2), day 4 (T3), day 9 (T4), and day 19 (T5); and postaltitude tests (T6) 7 to 10 days after return. On day 1 and day 19, a walk on a standardized hiking test route with oxygen saturation (SpO(2)) measure points was performed. Hemoglobin, packed cell volume, and red cell count showed changes over time, with higher values at T5 as compared to baseline. Reticulocyte count and erythropoietin (EPO) were increased at T2 and increased further until T5. EPO declined toward prealtitude values. P50-value (blood PO(2) at 50% hemoglobin oxygen saturation at actual pH) increased during the altitude sojourn (maximum increase at T5 by +0.40 kPa). At T5 all volunteers had a higher SpO(2) before, during, and at the end of the test route compared to T1. During adaptation to moderate altitude, persons with metabolic syndrome exhibit an increase in EPO and a rightward shift of the oxygen dissociation curve that is similar to healthy subjects.

Acclimatization↗

Acclimatization to altitude: effects on arterial oxygen saturation and pulse rate during prolonged exercise at altitude.

Changes in the arterial haemoglobin-oxygen saturation (SaO2) of the blood, in the blood pressure and in the heart rate, were monitored in subjects performing static exercise at an altitude of 3,600 metres before and after an acclimatization period of 28 days during an expedition to the Bolivian Andes. It was found that acclimatised subjects could maintain their SaO2 during prolonged exercise better than non-acclimatised subjects. The pulse rate of acclimatised subjects was consistently lower at the same work level than that of non-acclimatised subjects. Acclimatised subjects were able to reach higher levels of exercise than when they had first arrived at altitude. These data imply that acclimatization to altitude improves the delivery of oxygen to the tissues. The mechanism of this is not certain, but it may be concerned with a reduction in the degree of ventilation-perfusion inequality of the lung which occurs on exposure to high altitude.

Acclimatization↗

Pathological features of the lung in fatal high altitude pulmonary edema occurring at moderate altitude in Japan.

In order to characterize the pathological features of high altitude pulmonary edema (HAPE) occurring at moderate altitude in Japan, we performed routine hematoxylin and eosin (HE) staining in lung materials from HAPE autopsied cases. We also undertook advanced immunohistochemical staining for observation of type II pneumocytes, pulmonary surfactant (PS), and mast cells in the lung of HAPE cases to examine the biological changes within the lung parenchyma. The pathological findings of HAPE were characterized by alveolar edema, congestion of pulmonary vessels, alveolar hyaline membranes, alveolar hemorrhage, and multithrombi and fibrin clots, but maintained alveolar structure. The immunostaining results showed that the type II pneumocytes were cellular fusion, deformity, and exfoliation from the walls of alveoli; the PS not only lined the alveolar surface, but was also patchily distributed within alveoli; and the number of mast cells were increased (9.0 +/- 0.9 cells/mm(2)) compared to that in controls (1.1 +/- 0.4 cells/mm(2)) (p < 0.01). We conclude that the pathological features of HAPE at moderate altitude in Japan are similar to others reported worldwide, and that the type II pneumocytes, PS, and mast cells may contribute to some extent to pathophysiological parts in the development and progression of HAPE.

Adolescent↗

Effect of altitude on the lung function of high altitude residents of European ancestry.

The forced vital capacity (FVC), forced expiratory volume in one second (FEV), and ratio of FEV to FVC (%FEV) of 161 male and 158 female youths of European ancestry who were born at high altitudes and who were residing in La Paz, Bolivia (average altitude of 3,600 m) were examined and compared with those for lowland Europeans and highland Aymara Amerindians. FVC and FEV were significantly larger (p less than .001) in the La Paz Europeans than in two lowland control samples of European ancestry, with the relative differences between samples varying from small (1.5-4.1%) to moderate (7.7-11.9%). It could not be determined whether the enhanced lung volumes of the La Paz European children were acquired through an accelerated development of lung volumes relative to stature during adolescence, as is the case for Amerindian highlanders. After controlling for body and chest size, FVC and FEV were significantly smaller in the La Paz Europeans than in highland Aymara (p less than .001), suggesting that the lung volumes of the Aymara are influenced by factors other than simply growth and development at high altitude. Finally, as found in Amerindians, chest size is an important determinant of intra-individual variation in lung function among highland Europeans.

Adolescent↗

Re-evaluation of birth weights at high altitude. Study of babies born to mothers living at an altitude of 3,100 meters.

Babies born at altitudes above 2,700 meters have been reported to be below normal birth weight and small for gestational age (SGA). In a study of a specific community (Leadville, Colorado, altitude 3,100 meters) over a period of 14 months (ending November, 1978), 215 newborn infants were found to be appropriate for gestational age (AGA), with the entire group having a mean birth weight (3.16 kilograms) similar to that of newborn infants in Denver, Colorado (3.12 kilograms). This study from a community with a stable population indicates that babies born at high altitude are AGA. The increased morbidity which does occur for these babies is not due to SGA factors.

Altitude↗

[Acute mountain sickness and high-altitude pulmonary edema. How to protect the mountain climber from the effects of the "altitude haze"].

Acute mountain sickness (AMS) usually occurs after 6-12 hours of acute exposure to altitudes above 2,500 m. If there is no further altitude gain, it normally resolves spontaneously within a day or two. However, it may, in rare cases, progress to life-threatening cerebral edema. High-altitude pulmonary edema (HAPE) is a non-cardiogenic edema that is often preceded by symptoms of AMS. The major preventive measure is slow ascent. Acetazolamide and dexamethasone are effective in preventing AMS, while nifedipine is effective only against HAPE. Immediate descent and/or the administration of oxygen is the treatment of choice for both conditions. If this is not possible, dexamethasone may be given for severe AMS and nifedipine for HAPE.

Acetazolamide↗

The effect of acute hypoxia at low altitude and acute normoxia at high altitude on performance during a 30-s Wingate test in children.

The effect of acute hypoxia (FIO2 = 0.137 +/- 0.001) at Low Altitude (LA: Clermont-Ferrand, 330 m) and acute normoxia (FIO2 = 0.306 +/- 0.006) at High Altitude (HA: La Paz, 3600 m) on performance during a 30-s Wingate test has been investigated in prepubertal children (Tanner stage 1). Twenty five boys (LA, n = 10; HA, n = 15) aged from 10.6 to 12.7 years performed two Wingate tests at random: at LA, one in normoxia (ambient air) and one in acute hypoxia and at HA, one in chronic hypoxia (ambient air) and one in acute normoxia. The subjects performed the two tests using the same calibrated cycle ergometer. Peak Power (PP), Mean Power (MP), O2 uptake during the 30 s (VO2) and blood lactate accumulation (delta [L]s) were measured. Compared to normoxia, acute hypoxia at LA did not alter PP (8.0 +/- 1.1 vs 7.9 +/- 1.3 W.kg-1 BW) and MP (6.1 +/- 0.7 vs 6.1 +/- 1.1 W.kg-1 BW). Similarly, compared to chronic hypoxia, acute normoxia at HA did not modify these parameters (PP: 7.4 +/- 1.5 vs 7.3 +/- 1.8; MP: 5.4 +/- 1.2 vs 5.5 +/- 1.1; W.kg-1 BW). VO2 and delta [L]s were neither significantly changed by acute hypoxia at LA (520 +/- 50 vs 550 +/- 60 ml O2; 5.3 +/- 1.7 vs 4.8 +/- 1.7 mmol.l-1) nor by acute normoxia at HA (530 +/- 110 vs 500 +/- 90 ml O2; 3.4 +/- 1.3 vs 3.3 +/- 1.0 mmol.l-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗