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PubMed2001

Sun Valley summary. Consensus and action items Expedition Inspiration meeting 2000.

The fourth Expedition Inspiration conference was held March 21-23, 2000. While there are other conferences that concentrate on a particular facet of breast cancer, the design and goals of this conference are unusual. In order to maximize interaction of investigators and clinicians the meetings are small, invited, and private. The participants include both senior and junior physicians and scientists involved in clinical and basic research as well as clinical practice. The meetings serve four purposes: (i) Active discussion among participants who do not usually interact, (ii) Develop consensus as to the state of our knowledge as well as an action plan to stimulate future studies, (iii) Develop collaborative projects among the meeting participants, (iv) Foster new investigations by participants as well as others. This year immunology and the role of lymph nodes in breast cancer were the subject of the discussion. Investigators studying breast cancer biology, tumor immunity, potential cancer vaccines, and immunotherapy discussed potential therapeutic manipulation of the immune response to alter the natural history of breast cancer. Regional lymph nodes, the site of the immune response, are often affected early in the spread of breast cancer. For clinicians this involvement is central to planning effective treatment. The paradox that despite the involvement of these lymph nodes in mounting an immune response they are frequently the first site of breast cancer spread stimulated a great deal of discussion and some potentially interesting studies. The following consensus statement is the product of those discussions.

Breast Neoplasms↗
PubMed1997

After-effects of a high altitude expedition on blood.

The aim of the study was to investigate blood alterations caused by altitude acclimatization which last more than few days after return and might play a role for exercise performance at sea level. Measurements were performed in 12 mountaineers before, during and either 7/8 or 11/12 days after a Himalaya expedition (26-29 days at 4900 to 7600 m altitude). [Erythropoietin] rose only temporarily at altitude (max. +11 +/- 1 [SE] mu/ml serum). After return hemoglobin mass (initially 881 +/- 44 g, CO-Hb method) was increased by 14% (p < 0.01); aspartate aminotransferase activity in erythrocytes (initially 682 +/- 25 U/l) was augmented (day 7: +964 +/- 152 U/l, day 11: +533 +/- 107 U/l) indicating reduced mean cell age. Calculated blood volume (+14%) was influenced by red cell formation at altitude but also by plasma expansion at sea level. The half saturation pressure for Hb-O2 (pH 7.4, 37 degrees C) as well as the 2.3-diphosphoglycerate concentration were already initially high (32.1 +/- 0.5 mmHg, 20.5 +/- 0.7 mumol/g Hb) and showed only a nonsignificant tendency to increase after return. Also Hill's n was consistently high in the mountaineers, whereas the Bohr coefficients were slightly increased only after descent. Probably the preparatory physical training, partly in the Alps, and the stay in the Himalaya influenced O2-affinity for a prolonged time. The adaptations might reduce the loss of physical performance capacity at altitude and be part of altitude training effects.

Acid-Base Equilibrium↗
PubMedDate not supplied

Can a nurse trained in coronary care expedite emergency department management of patients with acute coronary syndromes?

OBJECTIVE: The goal of this study was to determine the effect of a coronary care-trained nurse (CCTN) on transfer times of patients presenting with acute coronary syndromes (ACS) from the emergency department (ED) to the coronary care unit (CCU) for definitive cardiac treatment (DCT). DESIGN: This was a prospective randomized controlled study. SETTING: The study took place in the ED of a metropolitan public teaching hospital in South Australia. PATIENTS: The study sample was comprised of 893 patients who presented to the ED with a complaint of chest pain. INTERVENTION: An experienced senior CCTN was randomly assigned to work in an ED for 16 randomly selected hours per week; comparable hours over the same period without a CCTN in attendance were used as control data. The major endpoint was time to CCU transfer where DCT was completed for patients with ACS. RESULTS: Out of 893 patients assessed as having possible ACS, 91 (10%) were admitted to the CCU, 47 with a diagnosis of unstable angina pectoris (UAP) and 44 with a diagnosis of acute myocardial infarction. Nineteen patients required thrombolysis and/or percutaneous coronary angioplasty. Mean times (in minutes) to transfer for DCT (95% CI) were 102 (70-134) and 117 (95-139) in the presence and absence of a CCTN, respectively, for all ACS, and 33 (10-55) and 54 (25-82), respectively, for acute myocardial infarction requiring thrombolysis and/or percutaneous coronary angioplasty. CONCLUSIONS: These pilot data show a nonsignificant trend suggesting that DCT is expedited by assignment of senior CCTNs to EDs and provides direction for further study.

Acute Disease↗
PubMed2004

The ORF3 protein of hepatitis E virus interacts with liver-specific alpha1-microglobulin and its precursor alpha1-microglobulin/bikunin precursor (AMBP) and expedites their export from the hepatocyte.

Hepatitis E virus (HEV), a plus-stranded RNA virus contains three open reading frames. Of these, ORF1 encodes the viral nonstructural polyprotein; ORF2 encodes the major capsid protein and ORF3 codes for a phosphoprotein of undefined function. Using the yeast two-hybrid system to screen a human cDNA liver library we have isolated, an N-terminal deleted protein, alpha(1) -microglobulin/bikunin precursor (AMBP) that specifically interacts with the ORF3 protein of HEV. Independently cloned, full-length AMBP was obtained and tested positive for interaction with ORF3 using a variety of in vivo and in vitro techniques. AMBP, a liver-specific precursor protein codes for two different unrelated proteins alpha(1)-microglobulin (alpha(1)m) and bikunin. alpha(1) m individually interacted with ORF3. The above findings were validated by COS-1 cell immunoprecipitation, His(6) pull-down experiments, and co-localization experiments followed by fluorescence resonance energy transfer analysis. Human liver cells showing co-localization of ORF3 with endogenously expressing alpha(1) m showed a distinct disappearance of the protein from the Golgi compartment, suggesting that ORF3 enhances the secretion of alpha(1)m out of the hepatocyte. Using drugs to block the secretory pathway, we showed that alpha m was not degraded in the presence of ORF3. Finally, (1)pulse labeling of alpha(1)m showed that its secretion was expedited out of the liver cell at faster rates in the presence of the ORF3 protein. Hence, ORF3 has a direct biological role in enhancing alpha(1)m export from the hepatocyte.

Alpha-Globulins↗
PubMed2003

Failure on Everest: the oxygen equipment of the spring 1952 Swiss expedition.

The Swiss expedition to Everest (altitude 8,848 m) in the spring of 1952 very nearly attained the summit with two of the climbers reaching 8,595 m. This would have been the first ascent of Everest. One main reason for failure was the inadequate oxygen equipment which was modified from sets designed for mine rescue using potassium peroxide generators. Oxygen could not be inhaled while the mountaineers were climbing because of the rigid mouthpiece assembly and the high breathing resistance of the equipment. It was argued that breathing oxygen during rest periods would suffice, but this was a fallacy as had been demonstrated by Kellas 30 years before.

Altitude↗
PubMed2003

Six selected cases from a year's experience as advisory doctor to a commercial mountaineering expedition company.

A review of six patients requiring medical assessment prior to joining commercial mountaineering trips. Medical problems encountered include malaria risk with immunosuppression, renal transplant recipients climbing at altitude, coronary artery disease risk at altitude, cardiac pacemaker function at altitude, and diabetes with remote-area travel. Cases also illustrate personal and commercial risk assessment and potential international differences in legal duty of care. It is hoped that these cases will stimulate debate and thought regarding the preventive aspects of altitude-related medical problems. This can be achieved by education of the general mountaineering population in altitude- and expedition-related medical matters, combined with individual pretrip advice for patients.

Adult↗
PubMed2000

Telemedicine at the top of the world: the 1998 and 1999 Everest extreme expeditions.

The National Aeronautics and Space Administration (NASA) initially established a Commercial Space Center (CSC) in the Department of Surgery at Yale University School of Medicine to further develop and evaluate technologies in information systems, telecommunications applied to medicine, and physiologic sensors. The CSC is known as the Medical Informatics and Technology Applications Consortium (MITAC). The overall purpose for this NASA program is to leverage technology, innovation, and resources from industry and academia through collaborative partnerships. The Yale-NASA CSC/MITAC organized the Everest Extreme Expeditions (E3) for the spring Himalayan climbing seasons in the years 1998 and 1999. The primary mission was to deliver advanced medical support with global telemedicine capabilities to one of the world's most remote and hostile settings--Mount Everest. The purpose was both humanitarian (providing medical support) and scientific (conducting medical and technology research). The Yale team provided medical care for the Everest Base Camp community; conducted validation experiments for several types of advanced medical technologies in this remote, hostile environment; and performed real-time monitoring of selected climbers, while also assessing the basic science of altitude physiology. Additionally, the teams conducted outreach medical care to the citizens of Nepal and provided several educational forums for a variety of medical and nonmedical personnel--including school-age children. As part of the project's mission, the E3 medical teams at both Nepal and New Haven were on a 24-hour emergency call system to deliver medical care in the event of a crisis. Unlike most of the teams at Everest, the mission of E3 was not to climb the 29,028-foot mountain the Nepalese call Sagarmatha ("Sky Head"). The mountain served as an extreme testing ground for telemedicine. The lessons learned from this testbed are reviewed here and further clarify the abilities to provide better health care in remote and extreme environments--which for some may even be their home environment during/after a medical illness.

Altitude Sickness↗
PubMed1996

Effect on serum lipids of monounsaturated oil and margarine in the diet of an Antarctic Expedition.

A 13-wk dietary intervention was carried out with 23 members of the 1991 wintering party of an Australian National Antarctic Research Expedition. Canola margarine and canola cooking oil were substituted for usual dietary fats (butter, a margarine containing 28% saturated fat, a polyunsaturated margarine, and vegetable oil). Mean energy intake slowly decreased although body weight slowly increased during the 42-wk wintering-over period. During 13 wk of dietary substitution, mean total cholesterol and low-density-lipoprotein-cholesterol concentrations fell by 7.0% and 10.0%, respectively (P < 0.05, repeated-measures ANOVA). These changes were not found in a second wintering-over group that did not experience this dietary intervention. The data indicate that a relatively simple change to the food supply has the potential to produce significant beneficial changes in lipoprotein lipid profile.

Adult↗
PubMed1988

Altitude insomnia: studies during an expedition to the Himalayas.

During an expedition to the Himalayas, we studied the sleep and respiration of six climbers. Three ingested acetazolamide (500 mg) daily throughout the climb and the other three ingested placebo. At high altitude (4,150-4,846 m), each subject ingested temazepam (10 mg) for one night and placebo for another. Acetazolamide improved sleep above 2,750 m, but it is uncertain whether this was due to sedation or to improvements in arterial oxygen saturation. Sleep was markedly disturbed in all subjects above 4,000 m. Temazepam improved sleep, and in subjects taking acetazolamide, it reduced sleep-onset latencies and increased sleep efficiency close to that of sea level values. These observations suggest that the prophylactic use of acetazolamide is likely to improve sleep in climbers and that a low dose of a benzodiazepine such as temazepam (10 mg) may be beneficial at high altitude. Studies are now needed to exclude any possibility of respiratory impairment at altitude before a firm recommendation can be made regarding the routine use of this hypnotic.

Acetazolamide↗
PubMed2005

Leveraging nurse-related dashboard benchmarks to expedite performance improvement and document excellence.

Using nursing quality benchmarks in operational dashboards and translating those data to drive performance excellence is a strategic imperative. Since access to unit-level, hospital-generated nurse-related benchmarks is an emerging arena, the authors provide an overview of aggregated trends and benchmarks gleaned from the California Nursing Outcome Coalition acute care database for 2 established nurse-related quality indicators-patient falls incidence and hospital-acquired pressure ulcer prevalence. Integrating these acute care benchmarks into clinical dashboards can be invaluable to clinicians, administrators, and policy makers who share a common commitment to expediting evidence-based improvement in patient care safety, outcomes, and excellence.

Accidental Falls↗
PubMed2005

Valacyclovir to expedite the clearance of recurrent herpes gladiatorum.

OBJECTIVE: To determine if valacyclovir usage expedites the clearance of recurrent herpes gladiatorum (HG) in wrestlers. DESIGN: Double-blind, placebo-controlled, prospective study using valacyclovir from September 2001 through March 2003. PARTICIPANTS: Twenty-nine wrestlers were recruited from the Minneapolis-St. Paul, Minnesota area. They ranged in ages from 18 to 36, of whom 7 were coaches and 22 active wrestlers. All participants had greater than 2-year history of recurrent HG. MAIN OUTCOME MEASURES: Upon an outbreak, all participants would swab the area on a daily basis for 14 days. Swabs were analyzed for herpes simplex virus 1/2 via PCR. End point was determined as the last sample with measurable PCR detected. Individuals were randomly selected, yet equally distributed, to be in 1 of 3 groups: placebo x 7 days, valacyclovir 500 mg BID x 7 days, or valacyclovir 1,000 mg QD x 7 days. RESULTS: Twenty participants (3 coaches and 17 active wrestlers) experienced outbreaks. All participants were compliant and started medication within 24 hours of developing symptoms. Valacyclovir usage showed significant reduction in mean time until PCR clearance, 8.14 days with placebo versus 6.43 days with valacyclovir 500 mg BID. CONCLUSIONS: A 7-day regimen of valacyclovir 500 mg BID will reduce the length of time until clinical clearance of an outbreak of recurrent HG. Its usage reduced duration of viral presence by 21%.

Acyclovir↗
PubMed2003

Expedited discharge in trauma patients requiring anticoagulation for deep venous thrombosis prophylaxis: the LEAP Program.

OBJECTIVE: With rising health care costs, methods to decrease length of hospital stay without compromising care are necessary. One area that extends length of stay in trauma patients is inpatient anticoagulation to a therapeutic international normalized ratio. The 1998 American College of Chest Physicians guidelines recommend thromboprophylaxis with low-molecular-weight heparin (LMWH) and oral warfarin in this population. The LMWH Expedited Anticoagulation Program (LEAP) was created with the following goals: to decrease the number of inpatient warfarin days and to reduce overall number of hospital days. METHODS: Inpatient anticoagulation was initiated with warfarin and LMWH. LEAP included early multidisciplinary collaboration to ensure third-party approval, outpatient primary care physician follow-up, and LMWH self-injection before discharge. Patients were discharged on LMWH (discontinued by primary care provider when a therapeutic international normalized ratio was attained) and warfarin (continued until resolution of orthopedic injuries). From August 2000 to August 2001, adult patients were included in the prospective study. Primary inclusion criteria were blunt acetabular fracture, bilateral lower extremity fracture, and contralateral upper and lower extremity fractures. Patients with similar injuries receiving warfarin for deep venous thrombosis prophylaxis between June 1999 and June 2000 were the control population. Anticoagulation care was similar for the study and control subjects. RESULTS: There were 182 patients evaluated for LEAP inclusion. After initial evaluation, 108 patients were enrolled in LEAP (Injury Severity Score of 13). There were 69 control subjects (Injury Severity Score of 13). The average number of inpatient warfarin days was decreased from 8.8 days to 5.0 days in the control and study populations, respectively (p < 0.0001). The average length of hospitalization was shortened from 17.3 days in the control group to 12.9 days in the study (LEAP) population (p < 0.002). CONCLUSION: LEAP has successfully decreased the number of inpatient days on warfarin and total hospital days for trauma patients requiring deep venous thrombosis prophylaxis. These results have substantially decreased health care costs and increased available hospital beds in this era of high hospital occupancy.

Adult↗
PubMed1986

Hemostatic factors and renin in Greenland Eskimos on a high eicosapentaenoic acid intake. Results of the Fifth UmanaK Expedition.

The Fifth UmanaK expedition compared the fatty acid composition of platelets, bleeding times before and after ingestion of acetylsalicylic acid, 24-hour urinary tetranorprostanedioate, creatinine and Na output, as well as plasma renin, serum electrolytes and antithrombin III in 20 Greenland Eskimos and 20 Danes. The results indicate that the prostaglandin production was not inhibited in the Eskimos, and that the antiaggregatory prostanoids predominate in Eskimos compared to Danes. Although blood pressure and 24-hour urinary Na output were similar, the plasma renin level was significantly higher in the Eskimos on a high eicosapentaenoic acid intake.

Adult↗
PubMed1989

Effects of altitude on atrial natriuretic peptide: the Bicentennial Mount Everest Expedition.

1. Overnight recumbent atrial natriuretic peptide levels were significantly elevated in all ten subjects of the Australian Bicentennial Mount Everest Expedition during the first week at 5400 m, during acclimatization. 2. Twenty-four hour urine volume and urine sodium increased markedly at altitude. 3. Plasma renin activity and plasma aldosterone levels decreased significantly at altitude. 4. No significant changes in plasma cortisol, plasma sodium or potassium, body temperature, systolic or diastolic blood pressure or heart rate were observed. 5. Although it was impossible to control or measure salt and water intake during the study, results suggest that atrial natriuretic peptide may be important in the reduction in renin and aldosterone levels and in the diuresis and natriuresis necessary to adapt to hypoxia at altitude.

Adult↗
PubMedDate not supplied

Muscle-derived stem cells used to treat skin defects prevent wound contraction and expedite reepithelialization.

Stem cells derived from adult tissues may serve as cell therapy to enhance the healing process in skin wounds. This study was designed to evaluate the use of autologous muscle-derived stem cells in an experimental skin wound model in terms of their efficiency at promoting tissue repair/regeneration. Muscle-derived cells obtained from the dorsal muscle of New Zealand rabbits were cultured in vitro for 2 weeks. The cell population was identified using the satellite markers CD34, m-cadherin and Myf5, and the proliferative capacity of the adult stem cells was determined. The population was then fluorescently labeled with PKH26 and seeded onto a circular 2 cm diameter defect created on the dorsal side of the ear of the rabbit from which the cells had been harvested. Similar defects on the contra lateral ears were left untreated to form the control group. Fourteen days later, specimens were taken for light, transmission, and scanning electron microscopy, as well as for immunolabeling with antibodies against vimentin, alpha-actin, desmin, myosin, fibronectin, and cytokeratin 14. Areas of wound contraction and reepithelialization were determined by image analysis. Wound contraction was significantly greater in the control than the treatment group (p<0.05); control specimens also showed more myosin expression. Reepithelialized areas were significantly greater in the treatment group (p<0.05). Control wounds showed nonepithelialized areas and inflammatory granulation tissue. Reepithelialization occurred as epidermal tongues of fusiform cells. Our findings indicate that the use of autologous stem cells on skin wounds expedites and improves the organism's natural healing process.

Animals↗
PubMed2001

Reduced oxygen uptake during steady state exercise after 21-day mountain climbing expedition to 6,194 m.

We investigated the effect of a 21-day climbing expedition to 6,194 m on the oxygen uptake (V022) and leg blood flow (LBF) responses to submaximal exercise in five healthy, fit men during two-leg kicking exercise a 0-W and 50-W. Tests were completed 1 week before and 3 days after altitued acclimatization. The adaptation of VO2 at exercise onset was described by the time to 63% of the new steady state. Steady state VO2 during 50-W exercise was less post-climb (1290+/- 29 mL/min, mean +/- SE) than pre-climb (1413+/- 63 mL/min, P <.05). VO2 adapted more slowly at the onset of 50-W exercise post climb. There were no differences in the steady state LBF during the 50-W exercise, the increase above baseline, or the adaptation post-climb. Respiratory exchange ratio was greater at 50-W post-climb compared to pre-climb. Reduced steady state V02 during exercise after exposure to high altitude is consistent with an increase in metabolic efficiency.

Acclimatization↗
PubMed2000

Human skeletal muscle exercise metabolism following an expedition to mount denali.

Chronic exposure to high altitude is known to result in changes in the mechanisms regulating O(2) delivery to the contracting muscle. However, the effects of acclimatization on metabolism in the contracting muscle cell remain unclear. In this study, we have investigated the hypothesis that acclimatization would result in a closer coupling between ATP utilization and ATP production and that the improved energy state would be accompanied by a reorganization of the metabolic pathways consisting of an increased oxidative and decreased glycolytic potential. Five men, mean age of 28 +/- 2 (SE) yr, performed a standardized, two-stage submaximal cycling task in normoxia for 20 min at each of 59 and 74% peak O(2) consumption before and 3-4 days after returning from a 21-day expedition to Mount Denali (6,194 m). Acclimatization was without effect in altering the resting values of the adenine nucleotides (ATP, ADP, AMP), inosine monophosphate (IMP), or phosphocreatine (PCr) in the vastus lateralis. During exercise (40 min) after acclimatization compared with preacclimatization, PCr was not as depressed (33.2 +/- 7.1 vs. 40.6 +/- 5.4 mmol/kg dry wt) and IMP (0.289 +/- 0.11 vs. 0. 131 +/- 0.03 mmol/kg dry wt) and lactate (26.1 +/- 6.2 vs. 18.6 +/- 8.8 mmol/kg dry wt) in contracting muscle were not as elevated (P < 0.05). Although no effect of acclimatization was observed for the maximal activity (mol. kg protein(-1). h(-1)) of citrate synthase (4. 76 +/- 0.44 vs. 4.94 +/- 0.45), lactate dehydrogenase was increased by 13% (36.5 +/- 2.6 vs. 41.2 +/- 3.1, P < 0.05). It is concluded that acclimatization results in an improved energy state in the contracting muscle when tested under normoxic conditions; however, these effects are not associated with a higher oxidative potential or a lower glycolytic potential as hypothesized.

Acclimatization↗