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Medicina Aeroespacial , Aviação , Doença da Descompressão , Humanos , Medicina Militar , Oxigenoterapia , Medição de RiscoRESUMO
Space medicine is fundamental to the human exploration of space. It supports survival, function and performance in this challenging and potentially lethal environment. It is international, intercultural and interdisciplinary, operating at the boundaries of exploration, science, technology and medicine. Space medicine is also the latest UK specialty to be recognized by the Royal College of Physicians in the UK and the General Medical Council. This review introduces the field of space medicine and describes the different types of spaceflight, environmental challenges, associated medical and physiological effects, and operational medical considerations. It will describe the varied roles of the space medicine doctor, including the conduct of surgery and anaesthesia, and concludes with a vision of the future for space medicine in the UK.Space medicine doctors have a responsibility to space workers and spaceflight participants. These 'flight surgeons' are key in developing mitigation strategies to ensure the safety, health and performance of space travellers in what is an extreme and hazardous environment. This includes all phases from selection, training and spaceflight itself to post-flight rehabilitation and long-term health. The recent recognition of the speciality provides a pathway to train in this fascinating field of medicine and is a key enabler for the UK Government's commercial spaceflight ambition.
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Medicina Aeroespacial/métodos , HumanosRESUMO
This study investigated, for the first time, the effects of simulated high altitude, following acute hypobaric hypoxia (HH), on simultaneous assessment of large artery stiffness and endothelial function and its inter-relationship to left ventricular (LV) diastolic function, pulmonary artery systolic pressure (PASP), and estimated PA vascular resistance (PVR). Ten healthy subjects were studied at baseline pre and following acute HH to 4800 m for a total of 180 minutes. Assessments of LV diastolic function, mitral inflow, estimated LV filling pressure (E/e'), PVR, and PASP were undertaken using transthoracic echocardiography. Simultaneous assessments of arterial stiffness index (SI), systemic vascular resistance (SVR), vascular tone, and endothelial function (reflective index [RI]) were performed using pulse contour analysis of the digital arterial waveform. Acute hypoxia led to a fall in SpO2 (98.1±0.7 vs. 71.8±7.1%; p=0.0002), SVR (1589.1±191.2 vs. 1187.8±248.7; p=0.004), and RI (50.8±10.3 vs. 33.0±6.5%; p=0.0008) with an increase in PASP (24.3±2.2 to 35.0±5.3 mmHg; p=0.0001) and estimated PVR (116.40±19.0 vs. 144.6±21.5; p<0.001). There was no rise in either SI (p=0.13), mitral early annular early e' filling velocity or E/e'. There was a significant inverse correlation between SpO2 and PASP (r=-0.77; p<0.0001), PVR (r=-0.57; p=0.008) and between the fall in SpO2 and change (Δ) in RI (baseline vs. 150 min, r=-0.52; p<0.001). There was a modest inverse correlation between ΔRI (lower ΔRI=worsening endothelial function) and ΔPAP (r=-0.55; p=0.10) and a strong inverse correlation between ΔRI and ΔPVR (r=-0.89; p=0.0007). Acute hypobaric hypoxia does not significantly alter large artery stiffness or cause overt LV diastolic function. However, the degree of hypoxia influences both the systemic endothelial and pulmonary vascular responses. This noted association is intriguing and requires further investigation.
Assuntos
Pressão Sanguínea , Endotélio Vascular/fisiopatologia , Hipóxia/fisiopatologia , Artéria Pulmonar/fisiologia , Rigidez Vascular , Função Ventricular Esquerda , Adolescente , Adulto , Altitude , Análise de Variância , Pressão Atmosférica , Diástole , Ecocardiografia , Frequência Cardíaca , Humanos , Masculino , Oximetria , Estudos Prospectivos , Resistência Vascular , Adulto JovemRESUMO
AIM: To examine the response of brain natriuretic peptide (BNP) and NT-proBNP to high altitude (HA) both at rest and following exercise. METHODS: We measured NT-proBNP and BNP and Lake Louise (LL) acute mountain sickness (AMS) scores in 20 subjects at rest in Kathmandu (Kat; 1300 m), following exercise and at rest at 4270 and 5150 m. RESULTS: BNP and NT-proBNP (pg ml(-1) , mean ± SEM) rose significantly from Kat (9.2 ± 2 and 36.9 ± 6.6, respectively) to arrival at 4270 m after exercise (16.6 ± 4 and 152 ± 56.1, P=0.008 and P<0.001, respectively) and remained elevated the next morning at rest (28.9 ± 9 and 207.4 ± 65.1, P = 0.004 and P<0.001 respectively). At 5150, immediately following ascent/descent to 5643 m, BNP and NT-proBNP were 32.3 ± 8.8 and 301.1 ± 96.3 (P=0.003 and P<0.001 vs. Kat, respectively) and at rest the following morning were 33.3 ± 9.7 and 258.9 ± 89.5 (P=0.008 and P=0.001 vs. Kat respectively). NT-proBNP and BNP correlated strongly at 5150 m (ρ 0.905, P<0.001 and ρ 0.914, P<0.001 for resting and post-exercise samples respectively). At 5150 m, BNP levels were significantly higher among the four subjects with severe (LL score>6) AMS (58.4 ± 18.7) compared with those without (BNP 22.7 ± 8.6, P=0.048). There were significant correlations between change in body water from baseline to 5150 m with both BNP and NT-proBNP (ρ 0.77, P=0.001, ρ 0.745, P=0.002 respectively). CONCLUSION: In conclusion, these data suggest that BNP and NT-proBNP increase with ascent to HA both after exercise and at rest. We also report the novel finding that BNP is significantly greater in those with severe AMS at 5150 m.
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Doença da Altitude/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Doença Aguda , Adulto , Altitude , Biomarcadores/sangue , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nepal , Descanso/fisiologiaRESUMO
Lung cancer remains the most common fatal malignancy in the Western world. Survival rates have only improved modestly over the past three decades and new approaches are urgently required. It is clear that a concerted effort to reduce cigarette smoking is required. However, about 10% of patients with lung cancer are never smokers, indicating genetic or other predisposition. Lung cancer screening programmes are being trialled to target high-risk populations. Genetic strategies will provide new methods for screening and predicting response to treatment. Current therapy for lung cancer has reached a plateau and novel agents have shown modest clinical efficacy. Understanding the mechanisms by which chronic inflammatory disorders such as chronic obstructive pulmonary disease contribute to lung cancer development will help to identify new biological targets and biomarkers of early disease. This review focuses on recent advances in lung cancer prevention and treatment.
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Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiologia , Adenocarcinoma/prevenção & controle , Adenocarcinoma/terapia , Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/prevenção & controle , Carcinoma Pulmonar de Células não Pequenas/terapia , Proliferação de Células , Detecção Precoce de Câncer/métodos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Estadiamento de Neoplasias/métodos , Pneumonia/fisiopatologia , Fatores de Risco , FumarRESUMO
Acute exposure to altitude principally encompasses aviation and space activities. These environments can be associated with very acute changes in pressure, oxygenation and temperature due to rates and magnitude of ascent that are not experienced in more chronic exposure such as mountaineering. The four key physiological challenges during acute exposure to altitude are: hypoxia (and hyperventilation), gas volume changes, decompression sickness and cold. The brief nature of aviation exposure to altitude provides little opportunity for acclimatisation, leading to markedly different effects when an individual is exposed to the same altitude acutely compared with an acclimatised individual climbing an 8000m (26 347ft) peak. Challenges such as hypobaric decompression sickness are not considered a hazard for chronic altitude exposure but are routine considerations for those flying to high altitude. Protective systems are essential for aircrew and passengers to survive and function during acute exposure to altitude.
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Medicina Aeroespacial , Altitude , Hipóxia/fisiopatologia , Pressão Atmosférica , Fenômenos Fisiológicos Cardiovasculares , Doença da Descompressão/etiologia , Doença da Descompressão/fisiopatologia , Humanos , Hiperventilação/etiologia , Hiperventilação/fisiopatologia , Hipóxia/etiologiaRESUMO
OBJECTIVES: To describe the demographics, referral mechanism and outcome of the emergency consultation in patients presenting to a secondary hospital emergency centre (EC). DESIGN: An observational study of patients presenting to an EC in a 1-month period from 19 November to 20 December 2007. SETTING: New Somerset Hospital, Cape Town, South Africa. SUBJECTS: All patients presenting alive to the EC during the study period who were seen by an EC doctor. OUTCOME MEASURES: A data collection form was completed by EC doctors at the time of the initial EC consultation documenting patient demographics, time and delay periods, South African Triage Score (SATS), initial diagnosis, transport and referral mechanisms and outcome of EC consultation. RESULTS: Data on 2646 patient presentations were described with a mix of SATS acuity levels (green: routine care; yellow: urgent; orange: very urgent; red: immediate), with more than one-third of presentations scoring an orange or red SATS. Most patients presented in the daytime, with an increase in more ill patients (higher SATS) later in the day and at night. The peak age group was 20-40 years, with 39% resident in informal settlements within 15 km of the hospital. The initial diagnosis was trauma in 26% of presentations, with a wide spread of other presentations. Patients were transported by ambulance to the EC in 39% of presentations, 41% were self-referred and 41% were referred by a primary health care practitioner. Fifty-three percent of presentations were either admitted to hospital or kept in the EC for further investigations, and the remainder were discharged from the EC. CONCLUSIONS: Clear trends are seen for patient demographics and temporal attendance patterns which are important for resource allocation and planning. Many low-acuity patients, largely non-referred, are being seen in the EC and should be managed by primary health care level staff outside the EC.
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Emergências/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Encaminhamento e Consulta , Características de Residência , África do Sul/epidemiologia , Fatores de Tempo , Transporte de Pacientes/estatística & dados numéricos , Resultado do Tratamento , Serviços Urbanos de Saúde/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: There are no general policies or protocols for procedural sedation in the emergency department and no literature on present practice in South Africa. AIMS: To investigate procedural sedation (PS) practice in adults in emergency departments (EDs) in Cape Town, South Africa. METHODS: A cross-sectional descriptive study was performed by interviewing all ED managers and ED doctors in Cape Town meeting the criteria (open 24 h a day, staffed by full-time doctors, seeing adult patients and doctors who practice primarily emergency medicine and have performed at least one PS in the last 3 months). RESULTS: Data were collected from 13 units (5 public, 8 private) and 76 clinicians (48 public, 28 private). PS facilities are generally good in the private sector, but poor in the public sector (lacking in equipment, staff and protocols). Monitoring of patients during PS is often substandard, with only two thirds of clinicians using a minimum of blood pressure and pulse oximetry monitors during PS. Commonly used drugs for PS included midazolam, morphine and propofol (91%, 80% and 28%, respectively). Propofol (use of which is increasing in the international ED) is more likely to be used by experienced clinicians and those in the private sector. Surprisingly, almost half of clinicians would like propofol used on themselves hypothetically, although the majority (62%) said they had no or limited knowledge of its use and were concerned with its safety. CONCLUSIONS: The private sector is generally better serviced for PS than the public sector. Most ED clinicians use morphine and midazolam for PS. However, there is widespread awareness of propofol as an alternative and probably superior PS drug. Recommendations for improving PS include development of general protocols for PS, training of doctors at all levels and optimization of ED facilities and staffing.
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PURPOSE: Lung cancer is the leading cause of cancer deaths in the developed world. Small cell lung cancer (SCLC) has the worst prognosis due to the emergence of resistance to chemotherapy. This article will review recent work that has defined mechanisms of chemo-resistance focusing on the role of integrins. RESULTS: SCLC is surrounded by an extensive stroma of extracellular matrix (ECM) and high levels of expression correlate with poor prognosis. ECM protects SCLC cells against chemotherapy-induced cell death by activating beta1 integrins leading to activation of phosphoinositide-3-OH kinase (PI3-kinase), which prevents etoposide-induced caspase-3 activation and subsequent apoptosis. Engagement of ECM prevents etoposide and radiation induced G2/M cell cycle arrest in SCLC cells by blocking the up-regulation of p21Cip1/WAF1 and p27Kip1 and the down-regulation of cyclins E, A and B. These effects are abrogated by pharmacological and genetic inhibition of PI3-kinase signalling. CONCLUSIONS: Thus, ECM via beta1 integrin-mediated PI3-kinase activation allows SCLC cells to survive treatment induced cell cycle arrest and apoptosis with persistent DNA damage, providing a model to account for the emergence of acquired drug resistance. Novel therapeutic strategies may therefore be directed at inhibiting integrin-mediated cell survival signals improving response rates and cure in this devastating cancer.
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Carcinoma de Células Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/fisiologia , Matriz Extracelular/fisiologia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/fisiopatologia , Carcinoma de Células Pequenas/radioterapia , Sobrevivência Celular , Humanos , Integrinas/fisiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/radioterapia , Modelos Biológicos , Prognóstico , Transdução de SinaisRESUMO
The emergence of resistance to chemotherapy remains a principle problem in the treatment of small-cell lung cancer (SCLC). We demonstrate that extracellular matrix (ECM) activates phosphatidyl inositol 3-kinase (PI3-kinase) signaling in SCLC cells and prevents etoposide-induced caspase-3 activation and subsequent apoptosis in a beta1 integrin/PI3-kinase-dependent manner. Crucially we show that etoposide and radiation induce G2/M cell cycle arrest in SCLC cells prior to apoptosis and that ECM prevents this by overriding the upregulation of p21(Cip1/WAF1) and p27(Kip1) and the downregulation of cyclins E, A and B. These effects are abrogated by pharmacological and genetic inhibition of PI3-kinase signaling. Importantly we show that chemoprotection is not mediated by altered SCLC cell proliferation or DNA repair. Thus, ECM via beta1 integrin-mediated PI3-kinase activation overrides treatment-induced cell cycle arrest and apoptosis, allowing SCLC cells to survive with persistent DNA damage, providing a model to account for the emergence of acquired drug resistance.
Assuntos
Apoptose , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Ciclo Celular , Matriz Extracelular/metabolismo , Integrina beta1/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Carcinoma de Células Pequenas/terapia , Adesão Celular , Linhagem Celular Tumoral , Dano ao DNA , Etoposídeo/farmacologia , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Laminina/metabolismo , Neoplasias Pulmonares/terapia , Mutação , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Vanadatos/farmacologiaRESUMO
BACKGROUND: Modern air travel entails a cabin altitude between 1520 and 2440 m (5000-8000 ft) and thus exposure to mild hypoxia. There is debate as to whether hypoxia is causally related to venous thromboembolism (VTE) occurring during or after travel. One study suggested that a short period of hypobaric hypoxia causes activation of coagulation. OBJECTIVES: To test the hypothesis that hypoxia alone (normobaric hypoxia) causes activation of coagulation, possibly through endothelial cell activation. METHODS: Six healthy male volunteers were exposed for 3 h, while seated, on two separate occasions to (i) dry air (control) and (ii) hypoxic gas mixture (12.8% O2 in N2, equivalent to breathing air at 3660 m [12000 ft]). RESULTS: There were no differences in hemostatic or endothelial markers between control and hypoxic groups, but platelet and leukocyte counts increased and were significantly higher in the hypoxic group. There were increases in fibrinogen and von Willebrand factor, as well as rheological changes, but these were not significantly different between control and hypoxic groups. CONCLUSIONS: This small study does not support the previous suggestion that hypoxia causes activation of coagulation, and suggests that immobility-induced rheological changes may be more significant in the etiology of VTE occurring during or after travel.