A pilot investigation into the effects of acute normobaric hypoxia, high altitude exposure and exercise on serum angiotensin-converting enzyme, aldosterone and cortisol.

INTRODUCTION: Aldosterone decreases at high altitude (HA) but the effect of hypoxia on angiotensin-converting enzyme (ACE), a key step in the renin-angiotensin-aldosterone system, is unclear. METHODS: We investigated the effects of exercise and acute normobaric hypoxia (NH, ~11.0% FiO2) on nine participants and six controls undertaking the same exercise at sea level (SL). NH exposure lasted 5 hours with 90 minutes of submaximal treadmill walking. Blood samples for aldosterone, ACE and cortisol were taken throughout exposure and at rest during a trek to HA (5140 m) in eight separate participants. RESULTS: There was no difference in cortisol or aldosterone between groups pre-exercise. Aldosterone rose with exercise to a greater extent at SL than in NH (post-exercise: 700 ± 325 versus 335 ± 238 pmol/L, mean ± SD, p = 0.044). Conversely, cortisol rose to a greater extent in NH (post-exercise: 734 ± 165 versus 344 ± 159 nmol/L, mean ± SD, p = 0.001). There were no differences in ACE activity. During the trek to HA, resting aldosterone and cortisol reduced with no change in ACE. CONCLUSIONS: Acute NH subdues the exercise-associated rise in aldosteroe but stimulates cortisol, whereas prolonged exposure at HA reduces both resting aldosterone and cortisol. As ACE activity was unchanged in both environments, this is not the mechanism underlying the fall in aldosterone.

Nutritional status and the gonadotrophic response to a polar expedition.

Polar expeditions have been associated with changes in the hypothalamic-pituitary-testicular axis consistent with central hypogonadism (i.e., decreased testosterone, luteinising hormone (LH), and follicle stimulating hormone (FSH)). These changes are typically associated with body mass loss. Our aim was to evaluate whether maintenance of body mass during a polar expedition could mitigate against the development of central hypogonadism. Male participants (n = 22) from a 42-day expedition (British Services Antarctic Expedition 2012) volunteered to take part in the study. Body mass, body composition, and strength data were recorded pre- and postexpedition in addition to assessment of serum testosterone, LH, FSH, thyroid hormones, insulin-like growth factor 1 (IGF-1), and trace elements. Energy provision and energy expenditure were assessed at mid- and end-expedition. Daily energy provision was 6335 ± 149 kcal·day(-1). Estimated energy expenditure midexpedition was 5783 ± 1690 kcal·day(-1). Body mass and percentage body fat did not change between pre- and postexpedition. Total testosterone (nmol·L(-1)) (14.0 ± 4.9 vs. 17.3 ± 4.0, p = 0.006), calculated free testosterone (pmol·L(-1)) (288 ± 82 vs. 350 ± 70, p = 0.003), and sex hormone binding globulin (nmol·L(-1)) (33 ± 12 vs. 36 ± 11, p = 0.023) concentrations increased. LH and FSH remained unchanged. Thyroid stimulating hormone (TSH; IU·L(-1)) (2.1 ± 0.8 vs. 4.1 ± 2.1, p < 0.001) and free triiodothyronine (FT3; IU·L(-1)) (5.4 ± 0.4 vs. 6.1 ± 0.8, p < 0.001) increased while free thyroxine, IGF-1, and trace elements remained unchanged. Hand-grip strength was reduced postexpedition but static lift strength was maintained. Maintenance of body mass and nutritional status appeared to negate the central hypogonadism previously reported from polar expeditions. The elevated TSH and free FT3 were consistent with a previously reported "polar T3 syndrome".

Cardiac biomarkers at high altitude.

BACKGROUND: Classically, biomarkers such as the natriuretic peptides (NPs) BNP/NT-proBNP are associated with the diagnosis of heart failure and hs-cTnT with acute coronary syndromes. NPs are also elevated in pulmonary hypertension. High pulmonary artery systolic pressure (PASP) is a key feature of high altitude pulmonary edema (HAPE), which may be difficult to diagnose in the field. We have previously demonstrated that NPs are associated with high PASP and the presence of acute mountain sickness (AMS) in a small cohort at HA. We aimed to investigate the utility of several common cardiac biomarkers in diagnosing high PASP and AMS. METHODS: 48 participants were assessed post-trekking and at rest at three altitudes: 3833 m, 4450 m, and 5129 m. NPs, hs-cTnT and hsCRP, were quantified using immunoassays, PASP was measured by echocardiography, and AMS scores were recorded. RESULTS: Significant changes occurred with ascent in NPs, hs-cTnT, hsCRP (all p<0.001) and PASP (p=0.006). A high PASP (≥40 mm Hg) was associated with higher NPs, NT-proBNP: 137±195 vs. 71.8±68 (p=0.001); BNP 15.3±18.1 vs. 8.7±6.6 (p=0.001). NPs were significantly higher in those with AMS or severe AMS vs. those without (severe AMS: NT-proBNP: 161.2±264 vs. 76.4±82.5 (p=0.008)). The NPs correlated with hsCRP. cTnT increased with exercise at HA and was also higher in those with a high PASP (13.8±21 vs. 7.8±6.5, p=0.018). CONCLUSION: The NPs and hs-cTnT are associated with high PASP at HA and the NPs with AMS.

Method for recovery and immunoaffinity enrichment of membrane proteins illustrated with metastatic ovarian cancer tissues.

Integral membrane proteins play key biological roles in cell signaling, transport, and pathogen invasion. However, quantitative clinical assays for this critical class of proteins remain elusive and are generally limited to serum-soluble extracellular fragments. Furthermore, classic proteomic approaches to membrane protein analysis typically involve proteolytic digestion of the soluble pieces, resulting in separation of intra- and extracellular segments and significant informational loss. In this paper, we describe the development of a new method for the quantitative extraction of intact integral membrane proteins (including GPCRs) from solid metastatic ovarian tumors using pressure cycling technology in combination with a new (ProteoSolve-TD) buffer system. This new extraction buffer is compatible with immunoaffinity methods (e.g., ELISA and immunoaffinity chromatography), as well as conventional proteomic techniques (e.g., 2D gels, western blots). We demonstrate near quantitative recovery of membrane proteins EDG2, EDG4, FASLG, KDR, and LAMP-3 by western blots. We have also adapted commercial ELISAs for serum-soluble membrane protein fragments (e.g., sVEGFR2) to measure the tissue titers of their transmembrane progenitors. Finally, we demonstrate the compatibility of the new buffers with immunoaffinity enrichment/mass spectrometric characterization of tissue proteins.

Stroke knowledge among urban and frontier first responders and emergency medical technicians in Montana.

PURPOSE: To assess stroke knowledge and practice among frontier and urban emergency medical services (EMS) providers and to evaluate the need for additional prehospital stroke training opportunities in Montana. METHODS: In 2006, a telephone survey of a representative sample of EMS providers was conducted in Montana. Respondents were stratified into 2 groups: those working in urban and frontier counties. FINDINGS: Compared to EMS providers from urban counties, those from frontier counties were significantly more likely to be older (mean age 44.7 vs 40.1 years), have fewer personnel working in their service (mean 17.7 vs 28.6), to be located farther away from a computed tomography scan (CT scan) (mean 41.3 vs 17.6 miles), and to be volunteers (84% vs 49%). They were also less likely to have a stroke protocol (58% vs 66%) and use a stroke screening tool (36% vs 47%) than their urban counterparts. There were no significant differences between frontier and urban EMS respondents' ability to correctly identify 4 or more stroke warning signs (58% vs 61%), 4 or more stroke risk factors (46% vs 43%), or the 3-hour recombinant tissue plasminogen activator (rt-PA) treatment window (56% vs 57%). Approximately two thirds of respondents from urban and frontier counties believed they had adequate stroke knowledge, but 90% indicated they were interested in additional stroke-related training. CONCLUSIONS: Although stroke knowledge did not differ between urban and frontier groups, stroke screens and stroke protocols were less likely to be used in the frontier areas. Training opportunities and the implementation of stroke protocols and screening tools are needed for EMS providers, particularly in frontier counties.

Availability of diagnostic and treatment services for acute stroke in frontier counties in Montana and Northern Wyoming.

CONTEXT: Rapid diagnosis and treatment of ischemic stroke can lead to improved patient outcomes. Hospitals in rural and frontier counties, however, face unique challenges in providing diagnostic and treatment services for acute stroke. PURPOSE: The aim of this study was to assess the availability of key diagnostic technology and programs for acute stroke evaluation and treatment in Montana and northern Wyoming. METHODS: In 2004, hospital medical directors or their designees were mailed a survey about the availability of diagnostic technology, programs, and personnel for acute stroke care. FINDINGS: Fifty-eight of 67 (87%) hospitals responded to the survey. Seventy-nine percent (46/58) of responding hospitals were located in frontier counties, with an average bed size of 18 (11 SD). Of the hospitals in frontier counties, 44% reported emergency medical services prehospital stroke identification programs, 39% had 24-hour computed tomography capability, 44% had an emergency department stroke protocol, and 61% had a recombinant tissue plasminogen activator protocol. Thirty percent of hospitals in frontier counties reported that they met 6-10 of the criteria established by the Brain Attack Coalition to improve acute stroke care compared to 67% of hospitals in the nonfrontier counties. CONCLUSION: A stroke network model could enhance care and improve outcomes for stroke victims in frontier counties.

Perceived risk for developing stroke among older adults.

BACKGROUND: Persons who perceive their risk for stroke accurately may be more likely to engage in prevention practices to reduce their risk. METHODS: In 2004, 800 adults aged 45 years and older in two counties participated in a telephone survey to assess their perceived risk for stroke and their history of stroke risk factors. RESULTS: Overall, 39% of respondents perceived themselves to be at risk for having a stroke. In the multivariate analyses, younger age, current smoking, and a history of diabetes, high blood pressure, high cholesterol, heart disease, and stroke/TIA were independently associated with perceived risk for stroke. Respondents with atrial fibrillation were no more likely to report being at risk for stroke compared to respondents without atrial fibrillation. Perceived risk for stroke increased as the number of risk factors increased. However, 46% of respondents with three or more risk factors did not perceive themselves to be at risk. CONCLUSIONS: Many adults with multiple risk factors do not perceive themselves to be at risk for stroke. Clinical and public health efforts are needed to increase awareness of the risk for stroke.

Rural community knowledge of stroke warning signs and risk factors.

INTRODUCTION: Rapid identification and treatment of ischemic stroke can lead to improved patient outcomes. Public education campaigns in selected communities have helped to increase knowledge about stroke, but most data represent large metropolitan centers working with academic institutions. Much less is known about knowledge of stroke among residents in rural communities. METHODS: In 2004, 800 adults aged 45 years and older from two Montana counties participated in a telephone survey using unaided questions to assess awareness of stroke warning signs and risk factors. The survey also asked respondents if they had a history of atrial fibrillation, diabetes, high blood pressure, high cholesterol, smoking, heart disease, or stroke. RESULTS: More than 70% of survey participants were able to correctly report two or more warning signs for stroke: numbness on any side of the face/body (45%) and speech difficulties (38%) were reported most frequently. More than 45% were able to correctly report two or more stroke risk factors: smoking (50%) and high blood pressure (44%) were reported most frequently. Respondents aged 45 to 64 years (odds ratio [OR] 2.44; 95% confidence interval [CI], 1.78-3.46), women (OR 2.02; 95% CI, 1.46-2.80), those with 12 or more years of education (OR 1.96; 95% CI, 1.08-3.56), and those with high cholesterol (OR 1.68; 95% CI, 1.17-2.42) were more likely to correctly identify two or more warning signs compared with respondents without these characteristics. Women (OR 1.48; 95% CI, 1.07-2.05) and respondents aged 45 to 64 years (OR 1.35; 95% CI, 1.01-1.81) were also more likely to correctly identify two or more stroke risk factors compared with men and older respondents. CONCLUSION: Residents of two rural counties were generally aware of stroke warning signs, but their knowledge of stroke risk factors was limited.