Nepal International Clinic

Kathmandu, Nepal

Nepal International Clinic

Kathmandu, Nepal
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Shrestha P.,Nepal International Clinic | Basnyat B.,Nepal International Clinic | Basnyat B.,Oxford Clinical Research Unit | Basnyat B.,Bern Medical | And 3 more authors.
High Altitude Medicine and Biology | Year: 2012

Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening medical condition. We describe a case of a 47-year-old woman who presented with headache, speech defects, and visual disturbances, and was later diagnosed with cerebral venous sinus thrombosis. The article describes a possible risk of such thrombotic events with exposure to high altitude environment in patients with coagulation defects such as Factor V Leiden mutation. Besides, such neurological conditions can occur independent of altitude illness and need to be recognized as their management differs. © 2012, Mary Ann Liebert, Inc.


Lucas S.J.E.,University of Otago | Burgess K.R.,University of Sydney | Lucas R.A.I.,University of Otago | Cotter J.D.,University of Otago | And 2 more authors.
Journal of Physiology | Year: 2011

Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2-4, 7-9 and 12-15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7-9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2-4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min-1 mmHg-1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity. © 2011 The Authors. Journal compilation © 2011 The Physiological Society.


Burgess K.R.,Peninsula Sleep Laboratory | Burgess K.R.,University of Sydney | Lucas S.J.E.,University of Otago | Shepherd K.,Peninsula Sleep Laboratory | And 9 more authors.
Sleep | Year: 2014

Study Objectives: To further our understanding of central sleep apnea (CSA) at high altitude during acclimatization, we tested the hypothesis that pharmacologically altering cerebral blood flow (CBF) would alter the severity of CSA at high altitude.Design: The study was a randomized, placebo-controlled single-blind study.Setting: A field study at 5,050 m in Nepal.Patients or Participants: We studied 12 normal volunteers.Interventions: Between days 5 to10 at high altitude, CBF velocity (CBFv) was increased by intravenous (IV) acetazolamide (10 mg/kg) and reduced by oral indomethacin (100 mg).Measurements and Results: Arterial blood gases, hypoxic and hypercapnic ventilatory responses, and CBFv and its reactivity to carbon dioxide were measured awake. Overnight polysomnography was performed. The central apnea-hypopnea index was elevated following administration of indomethacin (89.2 ± 43.7 to 112.5 ± 32.9 events/h; mean ± standard deviation; P < 0.05) and was reduced following IV acetazolamide (89.2 ± 43.7 to 47.1 ± 48.1 events/h; P < 0.001). Intravenous acetazolamide elevated CBFv at high altitude by 28% (95% confidence interval [CI]: 22-34%) but did not affect ventilatory responses. The elevation in CBFv was partly mediated via a selective rise in partial pressure of arterial carbon dioxide (PaCO2) (28 ± 4 to 31 ± 3 mm Hg) and an associated fall in pH (P < 0.01). Oral indomethacin reduced CBFv by 23% (95% CI: 16-30%), blunted CBFv reactivity, and increased the hypercapnic ventilatory response by 66% (95% CI: 30-102%) but had no effect on PaCO 2 or pH.Conclusion: Our findings indicate an important role for cerebral blood flow regulation in the pathophysiology of central sleep apnea at high altitude.


Subedi B.H.,Nepal International Clinic | Pokharel J.,Nepal International Clinic | Goodman T.L.,Himalyan Rescue Association | Amatya S.,Nepal International Clinic | And 4 more authors.
Wilderness and Environmental Medicine | Year: 2010

Steroids are used for the prevention and treatment of high-altitude illnesses. However, these agents can cause significant side effects. We report a case of altered mental status, gastrointestinal bleeding, skin rash, and avascular necrosis in a climber taking prophylactic dexamethasone prior to an attempt to climb Mt Everest. High-altitude cerebral edema (HACE), steroid toxicity, and acute adrenal crisis can have similar clinical presentations. Differentiating between these life-threatening conditions at high altitude is essential for successful treatment. © 2010 Wilderness Medical Society.


Bruno R.M.,CNR Institute of Clinical Physiology | Bruno R.M.,University of Pisa | Cogo A.,University of Ferrara | Ghiadoni L.,University of Pisa | And 10 more authors.
Atherosclerosis | Year: 2014

Residents of the Himalayan valleys uniquely adapted to their hypoxic environment in terms of pulmonary vasculature, but their systemic vascular function is still largely unexplored. The aim of the study was to investigate vascular function and structure in rural Sherpa population, permanently living at high altitude in Nepal (HA), in comparison with control Caucasian subjects (C) living at sea level. Methods and results: 95 HA and 64 C were enrolled. Cardiac ultrasound, flow-mediated dilation (FMD) of the brachial artery, carotid geometry and stiffness, and aortic pulse wave velocity (PWV) were performed. The same protocol was repeated in 11 HA with reduced FMD, after 1-h 100% O2 administration. HA presented lower FMD (5.18±3.10 vs. 6.44±2.91%, p=0.02) and hyperemic velocity than C (0.61±0.24 vs. 0.75±0.28m/s, p=0.008), while systolic pulmonary pressure was higher (29.4±5.5 vs. 23.6±4.8mmHg, p<0.0001). In multiple regression analysis performed in HA, hyperemic velocity remained an independent predictor of FMD, after adjustment for baseline brachial artery diameter, room temperature and pulse pressure, explaining 8.7% of its variance. On the contrary, in C brachial artery diameter remained the only independent predictor of FMD, after adjustment for confounders. HA presented also lower carotid IMT than C (0.509±0.121 vs. 0.576±0.122mm, p<0.0001), higher diameter (6.98±1.07 vs. 6.81±0.85mm, p=0.004 adjusted for body surface area) and circumferential wall stress (67.6±13.1 vs. 56.4±16.0kPa, p<0.0001), while PWV was similar. O2 administration did not modify vascular variables. Conclusions: HA exhibit reduced NO-mediated dilation in the brachial artery, which is associated to reduced hyperemic response, indicating microcirculatory dysfunction. A peculiar carotid phenotype, characterized by reduced IMT and enlarged diameter, was also found. © 2014 Elsevier Ireland Ltd.


PubMed | Nepal International Clinic, University of Pisa, University of Milan Bicocca, University of Ferrara and CNR Institute of Clinical Physiology
Type: Comparative Study | Journal: Atherosclerosis | Year: 2014

Residents of the Himalayan valleys uniquely adapted to their hypoxic environment in terms of pulmonary vasculature, but their systemic vascular function is still largely unexplored. The aim of the study was to investigate vascular function and structure in rural Sherpa population, permanently living at high altitude in Nepal (HA), in comparison with control Caucasian subjects (C) living at sea level.95 HA and 64 C were enrolled. Cardiac ultrasound, flow-mediated dilation (FMD) of the brachial artery, carotid geometry and stiffness, and aortic pulse wave velocity (PWV) were performed. The same protocol was repeated in 11 HA with reduced FMD, after 1-h 100% O2 administration. HA presented lower FMD (5.183.10 vs. 6.442.91%, p=0.02) and hyperemic velocity than C (0.610.24 vs. 0.750.28m/s, p=0.008), while systolic pulmonary pressure was higher (29.45.5 vs. 23.64.8mmHg, p<0.0001). In multiple regression analysis performed in HA, hyperemic velocity remained an independent predictor of FMD, after adjustment for baseline brachial artery diameter, room temperature and pulse pressure, explaining 8.7% of its variance. On the contrary, in C brachial artery diameter remained the only independent predictor of FMD, after adjustment for confounders. HA presented also lower carotid IMT than C (0.5090.121 vs. 0.5760.122mm, p<0.0001), higher diameter (6.981.07 vs. 6.810.85mm, p=0.004 adjusted for body surface area) and circumferential wall stress (67.613.1 vs. 56.416.0kPa, p<0.0001), while PWV was similar. O2 administration did not modify vascular variables.HA exhibit reduced NO-mediated dilation in the brachial artery, which is associated to reduced hyperemic response, indicating microcirculatory dysfunction. A peculiar carotid phenotype, characterized by reduced IMT and enlarged diameter, was also found.


Fan J.-L.,University of Otago | Burgess K.R.,University of New South Wales | Basnyat R.,Nepal International Clinic | Thomas K.N.,University of Otago | And 6 more authors.
Journal of Physiology | Year: 2010

An altered acid-base balance following ascent to high altitude has been well established. Such changes in pH buffering could potentially account for the observed increase in ventilatory CO2 sensitivity at high altitude. Likewise, if [H+] is the main determinant of cerebrovascular tone, then an alteration in pH buffering may also enhance the cerebral blood flow (CBF) responsiveness to CO2 (termed cerebrovascular CO2 reactivity). However, the effect altered acid-base balance associated with high altitude ascent on cerebrovascular and ventilatory responsiveness to CO2 remains unclear. We measured ventilation , middle cerebral artery velocity (MCAv; index of CBF) and arterial blood gases at sea level and following ascent to 5050 m in 17 healthy participants during modified hyperoxic rebreathing. At 5050 m, resting , MCAv and pH were higher (P < 0.01), while bicarbonate concentration and partial pressures of arterial O2 and CO2 were lower (P < 0.01) compared to sea level. Ascent to 5050 m also increased the hypercapnic MCAv CO2 reactivity (2.9 ± 1.1 vs. 4.8 ± 1.4% mmHg-1; P < 0.01) and CO2 sensitivity (3.6 ± 2.3 vs. 5.1 ± 1.7 l min-1 mmHg-1; P < 0.01). Likewise, the hypocapnic MCAv CO2 reactivity was increased at 5050 m (4.2 ± 1.0 vs. 2.0 ± 0.6% mmHg-1; P < 0.01). The hypercapnic MCAv CO2 reactivity correlated with resting pH at high altitude (R2= 0.4; P < 0.01) while the central chemoreflex threshold correlated with bicarbonate concentration (R2= 0.7; P < 0.01). These findings indicate that (1) ascent to high altitude increases the ventilatory CO2 sensitivity and elevates the cerebrovascular responsiveness to hypercapnia and hypocapnia, and (2) alterations in cerebrovascular CO2 reactivity and central chemoreflex may be partly attributed to an acid-base balance associated with high altitude ascent. Collectively, our findings provide new insights into the influence of high altitude on cerebrovascular function and highlight the potential role of alterations in acid-base balance in the regulation in CBF and ventilatory control. © 2010 The Authors. Journal compilation © 2010 The Physiological Society.


Brodmann Maeder M.M.,University of Bern | Basnyat B.,Nepal International Clinic | Stuart Harris N.,Massachusetts General Hospital
Wilderness and Environmental Medicine | Year: 2014

This article describes a private initiative in which professional Swiss rescuers, based at the foot of the Matterhorn, trained Nepalese colleagues in advanced high altitude helicopter rescue and medical care techniques. What started as a limited program focused on mountain safety has rapidly developed into a comprehensive project to improve rescue and medical care in the Mt Everest area for both foreign travelers and the local Nepalese people. © 2014 Wilderness Medical Society.


Jansen G.F.A.,University of Amsterdam | Basnyat B.,Nepal International Clinic
Journal of Cerebral Blood Flow and Metabolism | Year: 2011

Humans have populated the Tibetan plateau much longer than the Andean Altiplano. It is thought that the difference in length of occupation of these altitudes has led to different responses to the stress of hypoxia. As such, Andean populations have higher hematocrit levels than Himalayans. In contrast, Himalayans have increased circulation to certain organ systems to meet tissue oxygen demand. In this study, we hypothesize that cerebral blood flow (CBF) is higher in Himalayans than in Andeans. Using a MEDLINE and EMBASE search, we included 10 studies that investigated CBF in Andeans and Himalayans between 3,658 and 4,330 m altitude. The CBF values were corrected for differences in hematocrit and arterial oxygen saturation. The data of these studies show a mean hematocrit of 50% in Himalayans and 54.1% in Andeans. Arterial oxygen saturation was 86.9% in Andeans and 88.4% in Himalayans. The CBF in Himalayans was slightly elevated compared with sea-level subjects, and was 24% higher compared with Andeans. After correction for hematorit and arterial oxygen saturation, CBF was 20% higher in Himalayans compared with Andeans. Altered brain metabolism in Andeans, and/or increased nitric oxide availability in Himalayans may have a role to explain this difference in brain blood flow. © 2011 ISCBFM All rights reserved.


Hanaoka M.,Shinshu University | Droma Y.,Shinshu University | Basnyat B.,Nepal International Clinic | Ito M.,Shinshu University | And 4 more authors.
PLoS ONE | Year: 2012

Sherpas comprise a population of Tibetan ancestry in the Himalayan region that is renowned for its mountaineering prowess. The very small amount of available genetic information for Sherpas is insufficient to explain their physiological ability to adapt to high-altitude hypoxia. Recent genetic evidence has indicated that natural selection on the endothelial PAS domain protein 1 (EPAS1) gene was occurred in the Tibetan population during their occupation in the Tibetan Plateau for millennia. Tibetan-specific variations in EPAS1 may regulate the physiological responses to high-altitude hypoxia via a hypoxia-inducible transcription factor pathway. We examined three significant tag single-nucleotide polymorphisms (SNPs, rs13419896, rs4953354, and rs4953388) in the EPAS1 gene in Sherpas, and compared these variants with Tibetan highlanders on the Tibetan Plateau as well as with non-Sherpa lowlanders. We found that Sherpas and Tibetans on the Tibetan Plateau exhibit similar patterns in three EPAS1 significant tag SNPs, but these patterns are the reverse of those in non-Sherpa lowlanders. The three SNPs were in strong linkage in Sherpas, but in weak linkage in non-Sherpas. Importantly, the haplotype structured by the Sherpa-dominant alleles was present in Sherpas but rarely present in non-Sherpas. Surprisingly, the average level of serum erythropoietin in Sherpas at 3440 m was equal to that in non-Sherpas at 1300 m, indicating a resistant response of erythropoietin to high-altitude hypoxia in Sherpas. These observations strongly suggest that EPAS1 is under selection for adaptation to the high-altitude life of Tibetan populations, including Sherpas. Understanding of the mechanism of hypoxia tolerance in Tibetans is expected to provide lights to the therapeutic solutions of some hypoxia-related human diseases, such as cardiovascular disease and cancer. © 2012 Hanaoka et al.

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