***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The mechanism of high altitude headache ( HAH ) remains unknown . The aim of this study was to determine experimentally whether optic nerve sheath diameter ( ONSD ) , as an indicator of intracranial pressure , is related to HAH . Following sea level measurements at 3 and 12 hours ( SL ) , 23 subjects were passively transported to high altitude ( 3777 m , HA ) via cable car .  HAH , ONSD , arterial oxygen saturation ( Spo(2 ) ) , and fluid balance were determined at 3 , 12 , 24 , and 36 hours . After 12 hours exposure to HA , subjects were classified by visual analogue scale ( VAS ) as either HAH positive ( HAH+ ) or HAH negative ( HAH- ) . Acetazolamide ( 250 mg ) or placebo was then r and omly prescribed at 15 , 20 , and 28 hours . Outcome means were compared via analysis of variance , and relationships between variables were analyzed by longitudinal regression . Acetazolamide had no statistically significant effect on HAH ( p=0.63 ) or ONSD ( p=0.98 ) , but produced a negative fluid balance ( p<0.01 ) ( and also increased Spo(2 ) in exploratory analyses ) . Spo(2 ) was lower in HAH+ than HAH- [ 85 (3)% versus 88 (2)% , p=0.03 ) . Nevertheless , ONSD increased similarly in HAH+ and HAH- ( interaction p=0.90 ) . ONSD also remained significantly elevated above SL values for the entire HA period [ SL , 5.2 ( 0.5 ) versus HA , 5.6 ( 0.5 ) mm , p<0.01 ] , despite headache resolving with acclimatization [ VAS : SL , 1/100 ( 3 ) mm versus HA 3 h , 9/100 ( 13 ) ; 12 h , 10/100 ( 14 ) ; 24 h , 8/100 ( 12 ) ; 36 h , 1/100 ( 4 ) mm , p<0.01 ] . Furthermore , HAH was significantly correlated with Spo(2 ) ( β=-1.39 , p<0.01 ) but not with ONSD ( β=0.59 , p=0.57 ) . These data do not support that intracranial pressure is associated with the development or amelioration of mild HAH . Clinical trial registration NCT01288781 Our purpose was to study the preventive effect of the calcium channel blocker flunarizine on headache , postural ataxia , and memory deficits occurring during decompression to high altitude in a r and omized , placebo-controlled , double-blind study . After 7-day pretreatment with the study drugs , 20 healthy men were investigated at 490 m and 0.5 , 2 , 4 , and 6 h later at a  simulated altitude of 4559 m.  Headache severity was evaluated on a 4-point scale . Sway path and anteroposterior and lateral sway were recorded with open and closed eyes by static posturography . Short- and long-term memory was studied by testing the recall of verbal and figural material immediately and 2 h after presentation , respectively . Blood pressure ( BP ) and arterial oxygen saturation ( Sa(O2 ) ) were also assessed . Headache scores showed a trend to be lower in the flunarizine group that was significant after 4 and 6 h. Headache scores expressed as difference from baseline values showed a nonsignificant trend to be lower at 4 and 6 h in subjects treated with flunarizine . Postural stance , memory , BP , and Sa(O2 ) were similar in both treatment groups . Although the low number of investigated subjects may have prevented the detection of a significant therapeutic effect of flunarizine , the present data do not show that flunarizine is effective for prevention of headache , postural ataxia , and neurocognitive deficits occurring at simulated high altitude BACKGROUND Pulmonary edema results from a persistent imbalance between forces that drive water into the air space and the physiologic mechanisms that remove it . Among the latter , the absorption of liquid driven by active alveolar transepithelial sodium transport has an important role ; a defect of this mechanism may predispose patients to pulmonary edema . Beta-adrenergic agonists up-regulate the clearance of alveolar fluid and attenuate pulmonary edema in animal models . METHODS In a double-blind , r and omized , placebo-controlled study , we assessed the effects of prophylactic inhalation of the beta-adrenergic agonist salmeterol on the incidence of pulmonary edema during exposure to high altitudes ( 4559 m , reached in less than 22 hours ) in 37 subjects who were susceptible to high-altitude pulmonary edema . We also measured the nasal transepithelial potential difference , a marker of the transepithelial sodium and water transport in the distal airways , in 33 mountaineers who were prone to high-altitude pulmonary edema and 33 mountaineers who were resistant to this condition . RESULTS Prophylactic inhalation of salmeterol decreased the incidence of high-altitude pulmonary edema in susceptible subjects by more than 50 percent , from 74 percent with placebo to 33 percent ( P=0.02 ) . The nasal potential-difference value under low-altitude conditions was more than 30 percent lower in the subjects who were susceptible to high-altitude pulmonary edema than in those who were not susceptible ( P<0.001 ) . CONCLUSIONS Prophylactic inhalation of a beta-adrenergic agonist reduces the risk of high-altitude pulmonary edema . Sodium-dependent absorption of liquid from the airways may be defective in patients who are susceptible to high-altitude pulmonary edema . These findings support the concept that sodium-driven clearance of alveolar fluid may have a pathogenic role in pulmonary edema in humans and therefore represent an appropriate target for therapy OBJECTIVES To quantify the changes in ventilatory response and arterial blood gases in healthy male volunteers on acute ascent to 4578 meters altitude along with evaluating the role of acetazolamide and dexamethasone prophylaxis in acclimatisation . METHODS Forty four lowl and er male subjects participated as two groups in the study . Twenty four lowl and er healthy male adults ( age mean + /- SE 27.8 + /- 1.24 years ) comprised the non-acclimatised group . They were sub grouped in a double blind fashion into four . Each subgroup ( n=6 ) received placebo ( multivitamin ) or acetazolamide ( 250 mg ) or dexamethasone ( 4 mg ) or combined regimen of the two drugs twice daily for 5 days commencing 24 hours before ascent . The volunteers reached the altitude of 4578 meters within a span of one day . The second group ( acclimatised ) comprised of age and height matched twenty volunteers who had arrived 4 and 8 weeks earlier at the same altitude .  Arterial PO2 , PCO2 , SO2 and minute respiratory rate pH were measured . The pulmonary functions ( FVC , % FEV1 PEF , FEF(25 - 75 % ) and MVV ) were recorded by Compact Spirometer ( Vitalograph ) . Pre and post ascent measurements were carried out in non-acclimatised group whereas one measurement of the same parameters were made in acclimatised group . RESULTS The study revealed a significant increase in respiratory rate min-1 after 24 hours of ascent along with reduction in PaO2 and SaO2 . The gradual increase in PaO2 and SaO2 and reduction in PaCO2 was observed after 4 weeks at the same altitude . The reduction in FVC , % FEV1 , PEF , FEF(25 - 75 % ) and MW were recorded in our subjects after 24 hours of acute ascent . Nevertheless , all pulmonary parameters in volunteers having 8 weeks of stay at 4578 m altitude , were found equivalent to the non-acclimatised group . The greater increase in minute respiratory rate , PaO2 , SaO2 and pulmonary functions was found in volunteers taking acetazolamide . CONCLUSION It is concluded that hyperventilation and increase in lung volumes are the adaptive pulmonary responses which help in improving levels of PaO2 and SaO2 . The acetazolamide-dexamethasone prophylaxis appears beneficial in promoting pulmonary acclimatisation during hypobaric hypoxia Context Very few trials have evaluated ways to prevent high-altitude pulmonary edema ( HAPE ) . Contribution In this double-blind trial , 29 adults with a history of HAPE were r and omly assigned to receive prophylactic tadalafil , dexamethasone , or placebo during a 24-hour ascent and 2-day stay at 4559 m. Compared with placebo recipients , adults taking dexamethasone less often experienced acute mountain sickness and those taking either dexamethasone or tadalafil less often had HAPE . Caution s The trial involved a small number of selected adults who rapidly ascended to a high altitude . Implication s Either tadalafil or dexamethasone might help prevent HAPE in mountaineers with a history of pulmonary edema . The Editors Rapid ascent to altitudes greater than 2500 m may cause acute mountain sickness ( AMS ) and high-altitude pulmonary edema ( HAPE ) . In nonacclimatized mountaineers , the prevalences of AMS and HAPE at 4559 m are approximately 50 % and 4 % , respectively ( 1 ) . Individual susceptibility , rate of ascent , and preexposure to high altitude are major , independent determinants of the prevalence of AMS ( 2 ) . Acute mountain sickness is not a prerequisite for HAPE . Acetazolamide ( 3 , 4 ) or dexamethasone ( 5 , 6 ) prophylaxis can prevent AMS , whereas nifedipine prophylaxis can prevent HAPE ( 7 ) . Whether acetazolamide or dexamethasone also prevents HAPE has not been studied . Exaggerated hypoxic pulmonary vasoconstriction leading to elevated pulmonary capillary pressure ( 8) is the major pathophysiologic mechanism of HAPE . This elevated pulmonary capillary pressure may be caused by inhomogeneous hypoxic pulmonary vasoconstriction ( 9 ) , which leads to areas that are subjected to high pressure and flow , consequent mechanical overdistention of pulmonary capillaries , and injury of the bloodgas barrier ( 10 ) . This phenomenon causes extravasation of fluid , plasma proteins , and blood cells into the interstitial and alveolar spaces ( 11 ) . Decreased bioavailability of nitric oxide might explain the elevated pulmonary artery pressure ( 12 , 13 ) . Therefore , phosphodiesterase-5 inhibitors are an attractive option to restore impaired effects of nitric oxide in persons susceptible to HAPE ( 1416 ) . Constitutively impaired sodium and water transport in the lung has been thought to be an additional factor in the pathogenesis of HAPE ( 17 , 18 ) . Hypoxia also decreases water reabsorption from the alveolar space . Direct experimental evidence has been obtained from hypoxia-exposed rats ( 19 ) , and indirect evidence derives from decreased sodium transport activity in cultured alveolar epithelial cells ( 20 ) . Prophylactic inhalation of the 2-adrenergic agonist salmeterol to stimulate alveolar sodium transport ( 17 ) decreased the incidence of HAPE in susceptible persons . However , other mechanisms of action may also contribute to the preventive effects of salmeterol , because -adrenergics tighten the endothelial barrier and decrease pulmonary artery pressure ( 21 ) . Dexamethasone may be an alternative therapy to prevent HAPE because it stimulates alveolar sodium and water reabsorption ( 22 ) ; may enhance nitric oxide availability in pulmonary vessels ( 23 , 24 ) ; and is effective against AMS ( 5 , 6 ) , which may develop despite use of nifedipine as prophylaxis against HAPE ( 25 ) . However , HAPE has occurred in persons who received dexamethasone for AMS ( 26 , 27 ) . We sought to test whether prophylaxis with dexamethasone or tadalafil reduces the risk for HAPE in adults with a history of HAPE on rapid ascent to 4559 m. Methods Sample and Setting Mountaineers with a history of HAPE were recruited through announcements in the journals of the Swiss Alpine Club and the German Alpine Club . Four women and 25 men with at least 1 documented episode of HAPE participated after providing written informed consent . Table 1 shows the age and average number of HAPE episodes for each participant . No participant spent more than 4 nights above 2500 m within 30 days before ascent to the Capanna Regina Margherita , Italy ( altitude , 4559 m ) . Table 1 . Participant Characteristics Two to 4 weeks before the study at the Capanna Regina Margherita , baseline evaluations were performed in Zrich , Switzerl and ( altitude , 490 m ) . For ascent , participants traveled to Alagna , Italy ( altitude , 1100 m ) , ascended to 3200 m by cable car , and continued by foot to the Capanna Gnif 
    Output:
    
Our assessment of the most commonly-used pharmacological interventions suggests that acetazolamide is an effective pharmacological agent to prevent acute HAI in dosages of 250 to 750 mg/day .
Acetazolamide is associated with an increased risk of paraesthesia , although there are few reports about other adverse events from the available evidence .