Cardiovascular Risk Profiles and Pre-Existing Health Conditions of Trekkers in the Solu-Khumbu Region, Nepal

Background: High-altitude tourist trekking continues to grow in popularity on the Everest Trek in Nepal. We examined which pre-existing cardiovascular and health conditions these global trekkers had and what health issues they encountered during the trek, be it exacerbations of pre-existing conditions, or new acute ones. Method: Trekkers (n = 350) were recruited from guesthouses along the Everest Trek, mostly at Tengboche (3860 m). After completing a questionnaire on their health and travel preparation, they underwent a basic physical examination with an interview. Results: Almost half (45%) had pre-existing conditions, mostly orthopaedic and cardiovascular diseases. The average age was 42.7 years (range 18–76). The average BMI was 23.4 kg/m2, but 21% were overweight. A third were smokers (30%), and 86% had at least one major cardiovascular risk factor. A quarter (25%) were suffering from manifest acute mountain sickness (AMS), and 72% had at least one symptom of AMS. Adequate pre-travel examination, consultation, and sufficient personal preparation were rarely found. In some cases, a distinct cardiovascular risk profile was assessed. Hypertensive patients showed moderately elevated blood pressure, and cholesterol levels were favourable in most cases. No cardiovascular emergencies were found, which was fortunate as timely, sufficient care was not available during the trek. Conclusion: The results of earlier studies in the Annapurna region should be revalidated. Every trekker to the Himalayas should consult a physician prior to departure, ideally a travel medicine specialist. Preventative measures and education on AMS warrant special attention. Travellers with heart disease or with a pronounced cardiovascular risk profile should be presented to an internal medicine professional. Travel plans must be adjusted individually, especially with respect to adequate acclimatisation time and no physical overloading. With these and other precautions, trekking at high altitudes is generally safe and possible, even with significant pre-existing health conditions. Trekking can lead to invaluable personal experiences. Since organized groups are limited in their flexibility to change their itinerary, individual trekking or guided tours in small groups should be preferred

Anti-TNFR1 treatment on the day of immunization resulted in a significant reduction in demyelination and neuronal loss and a mild reduction in inflammatory infiltration.

<p>Spinal cord histopathology was performed at day 21 of EAE, following treatment with anti-mouse TNFR1 on the day of immunization. Representative images are shown from control IgG treated mice, with an EAE score of 2.0 (<b>B, E, H</b>, and <b>K</b>) and from anti-TNFR1-treated animals, with an EAE score of 1.0 (<b>C, F, I</b> and <b>L</b>). The level of spinal cord demyelination was assessed using sections stained with LFB (<b>A–C</b>). Mice treated prophylactically with anti-TNFR1 had significantly reduced levels of demyelination compared to control-treated mice (<b>A–C</b>). Immunohistochemistry with an anti-CD3 antibody was used to detect T cells and showed a decrease, although not significant, in the number of T cells within the spinal cord of anti-TNFR1 treated mice, in comparison to control animals (<b>D–F</b>). Immunohistochemistry with an antibody to Mac-3 was used to detect activated microglia and macrophages and demonstrated a decrease in the number of positive cells in anti-TNFR1 treated mice, although again this was not significant (<b>G–I</b>). <b>J-L</b>: Immunohistochemistry with an anti-NeuN antibody was used to detect neuronal cell bodies, which were quantified within the spinal cord grey matter. Anti-TNFR1 treated mice had significantly elevated numbers of surviving neuronal cell bodies. Scale bars in <b>B, C, E, F, H, I, K, L</b>: 200 µm.</p

Administration of anti-mouse TNFR1 on the day of immunization ameliorated EAE.

<p>Anti-mouse TNFR1 was injected intra-peritoneally in C57BL/6 mice, on the day of disease induction, at a dosage of 100 µg (equivalent to 5 mg/kg). Mice were subsequently monitored on a daily basis until 21 days after the onset of clinical symptoms (EAE day 21). Antibody treatment resulted in a reduced EAE severity compared to mice receiving control IgG (<b>A, B</b>). Furthermore, mice injected with anti-TNFR1 also showed a significant delay in the onset of spinal cord symptoms in comparison to mice receiving control IgG (<b>C</b>). (A) Results from one representative experiment out of four shown (control IgG n = 4; anti TNFR1 n = 6), (B, C) results from four combined experiments (control IgG n = 16, anti-TNFR1 n = 19). * P<0.05, **P<0.01.</p

Anti-TNFR1 inhibited acute TNF toxicity <i>in vitro</i> and <i>in vivo</i>.

<p>L929 cells were incubated with recombinant mouse TNF in the presence or absence of 10 µg/ml anti-TNFR1 (<b>A</b>) or with anti-TNFR1 in the presence of 0.1 ng/ml mouse TNF (<b>B</b>) and cell survival was determined by crystal violet staining. <b>C, D</b>: Female C57BL/6 wild type mice were pretreated with PBS or anti-TNFR1 (10 mg/kg, i.p.). After 2 h, PBS or murine TNF were injected i.v. (1 mg/kg) and body temperature (<b>C</b>) as well as survival of animals (<b>D</b>) were determined.</p

Anti-TNFR1 treatment reduced EAE severity in a therapeutic setting.

<p>EAE was induced in C57BL/6 mice with MOG^35–55 and mice were assessed for neurological symptoms on a daily basis. 400 µg (equivalent to 20 mg/kg) anti-mouse TNFR1 was injected i.p. either once on the day of EAE onset, or twice; firstly on the day of EAE onset and again on day 4 of the disease. Control mice received two injections of control IgG on days 1 and 4 of EAE. Mice receiving two injections of anti-TNFR1 had significantly reduced neurological symptoms than mice receiving control IgG (<b>A</b>, <b>B</b>). Spinal cords were examined histopathologically at day 14 of EAE by LFB staining (<b>C</b>–<b>E</b>). Control IgG-treated mice (<b>D</b>, image from animal with an EAE score of 2.5) had more demyelination than mice treated with two injections of anti-TNFR1 (<b>E</b>, image from animal with an EAE score of 0.5), although this was not found to be statistically significant. Immunohistochemistry with an anti-CD3 antibody showed no difference in the number of T cells within the spinal cord of control IgG-treated animals (<b>F</b>, <b>G</b>, image from an animal with an EAE score of 2.5) and anti-TNFR1 treated mice (<b>H</b>, image from an animal with an EAE score of 2.0). Immunohistochemistry with an antibody to Mac-3 also demonstrated no difference in the number of activated microglia/macrophages within the spinal cord of control IgG-treated animals (<b>I</b>, <b>J</b>, image from an animal with an EAE score of 2.5) and anti-TNFR1 treated mice (<b>K</b>, image from an animal with an EAE score of 2.0). <b>L</b>–<b>N</b>: Immunohistochemistry with an antibody against NeuN showed a statistically non-significant trend towards neuroprotection in the anti-TNFR1-treated mice (<b>M</b>, image from a control IgG-treated animal with an EAE score of 1.5), (<b>N</b>, image from an anti-TNFR1-treated animal with an EAE score of 1.5). Scale bars in <b>D</b>, <b>E, G, H, J, K, M, N</b>: 200 µm. * P<0.05. Control IgG n = 9; anti-TNFR1: 1 injection n = 4; anti-TNFR1: 2 injections n = 8.</p