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2.
Anaesthesia ; 78(4): 532, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36480421
3.
Anaesthesia ; 77(12): 1386-1394, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36130830

RESUMO

Average pre-operative fasting times for clear liquids are many times longer than those specified in national and international guidelines. We sought to decrease fasting times by applying a quality management tool aimed at continuous improvement. Through the application of iterative 'plan-do-study-act' cycles, tools to reduce pre-operative liquid fasting times were developed and applied, the effects measured, analysed and interpreted and the conclusions used to inform the next plan-do-study-act cycle. The first step was the introduction of unrestricted drinking until the patient was called to the operating theatre, with training of anaesthetic staff, adaption of local standard procedures and verbal information for patients. This did not result in short liquid fasting times, median (IQR [range]) 12.0 (9.5-14.0 [0.8-23.5]) h. In the second cycle, fasting cards were introduced as a subliminal written training tool for staff, patients and their relatives. This enabled short liquid fasting times to be achieved for outpatients (2.6 (0.8-5.1 [0.3-16]) h) and pre-admission patients (3.4 (1.8-9.4 [0.2-17.2]) h), but not for inpatients (6.5 (2.0-11.7 [0.2-16.2]) h). The third cycle included lectures for ward staff, putting up information posters throughout the hospital, revision of all written materials and provision of screencasts on the homepage for staff and patients. This decreased median liquid fasting time to 2.1 (1.2-3.8 [0.4-18.8]; p < 0.0001) h, with inpatients having the shortest fasting time of 1.4 (1.1-3.8 [0.4-18.8]) h. Repeated quality improvement cycles, adapted to local context, can support sustained reductions in pre-operative liquid fasting times.


Assuntos
Cuidados Pré-Operatórios , Melhoria de Qualidade , Humanos , Cuidados Pré-Operatórios/métodos , Ingestão de Líquidos , Jejum , Salas Cirúrgicas
4.
Int J Obstet Anesth ; 29: 73-80, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27890467

RESUMO

We present a case of a Jehovah's Witness patient who refused blood products, with the exception of albumin and clotting factors, and underwent cesarean section under spinal anesthesia complicated by postpartum hemorrhage. She was fluid resuscitated and treated with multiple uterotonics and internal iliac artery embolization. Because of agitation she required emergency tracheal intubation. Her hemoglobin concentration dropped from a preoperative value of 12mg/dL to 3mg/dL on postoperative day one. She was acidotic, requiring vasopressors for hemodynamic stability and remained ventilated and sedated. She was treated with daily erythropoietin, iron therapy and cyanocobalamin. Because of ongoing hemorrhage, continued acidemia and vasopressor requirements she was co-treated with PEGylated carboxyhemoglobin bovine and hyperbaric oxygen therapy to reverse her oxygen debt. On postoperative day eight her hemoglobin concentration was 7mg/dL, she was hemodynamically stable and vasopressors were discontinued. She was extubated and discharged from the intensive care unit on postoperative day eight. This report highlights the multiple modalities used in treating a severely anemic patient who refused blood, the use of an investigational new drug, the process of obtaining this drug via the United States Food and Drug Administration emergency expanded access regulation for single patient clinical treatment, and ethical dilemmas faced during treatment.


Assuntos
Anemia/terapia , Carboxihemoglobina/uso terapêutico , Cesárea , Oxigenoterapia Hiperbárica/métodos , Testemunhas de Jeová , Hemorragia Pós-Parto/terapia , Adulto , Feminino , Humanos
5.
Anaesthesist ; 64(1): 7-15, 2015 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-25601588

RESUMO

Since the development of the classic laryngeal mask airway (LMA) in the late 1980s, there has been a continuous increase in the frequency of its use as well as areas of application. While contraindications to its use for elective procedures must be recognized, there are an increasing number of clinical studies on expanded indications for the use of supraglottic airway (SGA) devices, particularly those of the second generation. The present article describes the added features of the second generation LMAs, with special emphasis on the behavior of these devices in position and performance tests. An appraisal is conducted based on the currently available literature on the value of the utility for indications, such as prolonged use, laparoscopic surgery, obesity, prone position and Cesarean section.


Assuntos
Anestesiologia/instrumentação , Anestesiologia/tendências , Máscaras Laríngeas , Humanos , Laringe/anatomia & histologia , Obesidade/complicações , Respiração Artificial/instrumentação
6.
Anaesthesist ; 61(2): 148-55, 2012 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-22354403

RESUMO

Expiratory carbon dioxide (CO(2)) monitoring is a valuable tool in the prehospital setting. Recent reports of misplaced endotracheal tubes in the prehospital setting make it important to ensure that tube placement is verified by CO(2) monitoring. The Euronorm 2007:1789 made provision of capnometry mandatory for all medical vehicles. However, the frequency of utilization of CO(2) monitoring after securing the airway and in patients with respiratory insufficiency is low. This article covers the terminology, physiology, technology and clinical applications of CO(2) monitoring. Monitoring of cardiac output and the efficiency of cardiopulmonary resuscitation are described and the article also highlights the importance of CO(2) monitoring in patients with severe head trauma as well as restrictive and obstructive pulmonary disorders.


Assuntos
Dióxido de Carbono/metabolismo , Monitorização Transcutânea dos Gases Sanguíneos , Dióxido de Carbono/sangue , Débito Cardíaco/fisiologia , Reanimação Cardiopulmonar , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/terapia , Serviços Médicos de Emergência , Hemodinâmica/fisiologia , Humanos , Intubação Intratraqueal , Pulmão/fisiopatologia , Pneumopatias/sangue , Pneumopatias/terapia , Monitorização Fisiológica , Insuficiência Respiratória/sangue , Insuficiência Respiratória/metabolismo , Insuficiência Respiratória/terapia
7.
Anaesthesist ; 59(6): 555-63, 2010 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-20502847

RESUMO

Extraglottic airway devices (EGA) are not only used in routine anaesthesia practice, they also have a distinct value for in-hospital and out-of-hospital difficult airway management. In the environment of the intensive care unit (ICU) EGA are not used on a regular basis. However, expertise and knowledge regarding EGA coming from the operating theatre or the out-of-hospital setting may also be of value for the ICU setting. This review presents the potential indications for EGA on the ICU for the management of difficult airway situations as well as during percutaneous tracheotomy. Furthermore, the possible advantages of EGA during postoperative recovery from anaesthesia as well as termination of controlled ventilation for intensive care patients are discussed.


Assuntos
Anestesia , Cuidados Críticos/métodos , Traqueotomia/instrumentação , Período de Recuperação da Anestesia , Unidades de Terapia Intensiva , Máscaras Laríngeas , Cuidados Pós-Operatórios , Respiração Artificial/instrumentação
8.
Acta Psychiatr Scand ; 116(5): 386-93, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17919158

RESUMO

OBJECTIVE: To test the effects of father's alcoholism on the development and remission from alcoholic drinking by age 40. METHOD: Subjects were selected from a Danish birth cohort that included 223 sons of alcoholic fathers (high risk; HR) and 106 matched controls (low risk; LR). Clinical examinations were performed at age 40 (n = 202) by a psychiatrist using structured interviews and DSM-III-R diagnostic criteria. RESULTS: HR subjects were significantly more likely than LR subjects to develop alcohol dependence (31% vs. 16%), but not alcohol abuse (17% vs. 15%). More subjects with alcohol abuse were in remission at age 40 than subjects with alcohol dependence. Risk did not predict remission from either alcohol abuse or alcohol dependence. CONCLUSION: Familial influences may play a stronger role in the development of alcoholism than in the remission or recovery from alcoholism.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , Filho de Pais com Deficiência/psicologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/epidemiologia , Alcoolismo/psicologia , Alcoolismo/reabilitação , Criança , Filho de Pais com Deficiência/estatística & dados numéricos , Estudos de Coortes , Estudos Transversais , Dinamarca , Humanos , Estudos Longitudinais , Masculino , Fenótipo , Fatores de Risco , Temperança/psicologia , Temperança/estatística & dados numéricos , Resultado do Tratamento
9.
Anaesthesist ; 56(6): 587-91, 2007 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-17375268

RESUMO

Treatment of patients suffering from decompensated chronic pulmonary disease (COPD) not responding to pharmacological therapy is still a major challenge in intensive care medicine. Administration of volatile anaesthetics may be a therapy of last resort in these cases. We report on a 65-year-old woman suffering from exacerbated COPD, who could not be sufficiently ventilated despite comprehensive pharmacological therapy. In order to administer a volatile anaesthetic in the ICU, we employed the "Anaesthetic Conserving Device" (AnaConDa) consisting of a vaporizer chamber embedded in a charcoal filter system. With this device, every standard intensive care ventilator can be used to deliver volatile anaesthetics in a safe and economic manner. The AnaConDa converts the open breathing system of the intensive care ventilator into a de facto half-closed system. The very low pulmonary compliance of the patient increased dramatically after administration of 0.75 vol% halothane for 48 h (27 vs. 150 ml/mbar). Elimination of CO(2) was improved and weaning from controlled ventilation was achieved. After surgical removal of a pulmonary abscess and a total of 78 days of intensive care therapy, the patient was discharged in good health.


Assuntos
Anestesia com Circuito Fechado/instrumentação , Anestesia por Inalação/instrumentação , Doença Pulmonar Obstrutiva Crônica/terapia , Ventiladores Mecânicos , Idoso , Anestésicos Inalatórios/administração & dosagem , Dióxido de Carbono/sangue , Cuidados Críticos , Feminino , Halotano/administração & dosagem , Humanos , Complacência Pulmonar/fisiologia , Mecânica Respiratória
11.
Resuscitation ; 73(3): 412-6, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17343972

RESUMO

AIM OF THE STUDY: Airway control is a potentially lifesaving procedure but tracheal intubation by direct laryngoscopy is difficult. This pilot study was conducted to determine whether tracheal intubation was more rapid and the success rate higher using an intubating laryngeal mask airway. MATERIAL AND METHODS: The success rates of 119 medical students without prior airway management experience in ventilating and then intubating the trachea of a Laerdal Airway Management Trainer with two different methods were compared. The methods were bag-mask ventilation (BM-V) followed by laryngoscopic intubation (LG-TI), and intubating laryngeal mask ventilation (ILMA-V) followed by ILMA-guided tracheal intubation (ILMA-TI). After an introductory lecture and demonstration, each student was allowed three attempts to intubate using each method in random order. RESULTS: All participants were successful with BM-V and ILMA-V on the first attempt. Laryngoscopic tracheal intubation was achieved by 60 (50.4%), 31 (26.1%) and 12 (10.1%) participants on the first, second and third attempt, respectively, while 16 (13.4%) failed in all three attempts. In the ILMA-TI group, 107 (90.0%), 10 (8.4%) and 2 (1.6%) succeeded on the first, second and third attempt, respectively. None failed. The intergroup difference is highly significant (p<0.001). Male participants were more successful with LG-TI than female (p<0.01), but not with ILMA-TI. CONCLUSION: Laryngoscopic orotracheal intubation is difficult for the untrained, but all participants were successful with ILMA-TI. These data suggest that alternative devices such as the ILMA should be included in the medical school curriculum for airway management.


Assuntos
Intubação Intratraqueal/métodos , Máscaras Laríngeas , Laringoscopia/normas , Estudos Cross-Over , Educação Médica , Feminino , Humanos , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/normas , Masculino , Manequins , Projetos Piloto , Estudantes de Medicina
12.
Anaesthesist ; 56(1): 53-62, 2007 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-17077933

RESUMO

Since 1st October 2003 the new German "Approbationsordnung für Arzte" (Medical Licensing Regulations) requires an increasing amount of small group teaching sessions and encourages a multidisciplinary and more practical approach to the related topics. In 2004 the German Society of Anaesthesiology and Intensive Care Medicine has provided almost all anaesthesia faculties of German Universities with equipment for full-scale simulation. This article describes methods for a simulation-based medical education training program. Basic requirements for a successful training program using full scale simulators are the provision of an adequate logistical and material infrastructure, teacher attendance of train-the-trainer courses, implementation in the medical curriculum and an instructor-student ratio of 1:3, equivalent to that for bedside teaching. If these requirements were fulfilled, medical students scored the simulation scenarios "induction of anaesthesia", "acute pulmonary embolism", "acute management of a multiple trauma patient" and "postoperative hypotension" as 1.5, 1.6, 1.5 and 1.5, respectively, on a scale of 1-6. These scores were better than those given for other segments of the curriculum.


Assuntos
Anestesiologia/educação , Educação Médica/métodos , Simulação de Paciente , Anestesia , Baixo Débito Cardíaco/terapia , Cuidados Críticos , Currículo , Educação Médica/normas , Alemanha , Humanos , Traumatismo Múltiplo/terapia , Complicações Pós-Operatórias/terapia , Embolia Pulmonar/terapia
13.
Anaesthesist ; 55(11): 1189-96, 2006 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-16953421

RESUMO

The serotonin syndrome is caused by a drug-induced increase of the intrasynaptic serotonin concentration. Milder forms of the syndrome may be difficult to diagnose because of the variability of symptoms. Severe forms often rapidly turn into a life-threatening situation, therefore the serotonin syndrome may be a challenge for physicians. We describe the pathophysiology and therapeutic options of the serotonin syndrome and report about a 42-year-old female patient who ingested large amounts of moclobemide, a monoamine oxidase inhibitor, and citalopram, a selective serotonin reuptake inhibitor, for attempted suicide. Within a few hours the patient developed a lethal serotonin syndrome although ICU therapy was initiated immediately.


Assuntos
Citalopram/efeitos adversos , Moclobemida/efeitos adversos , Inibidores da Monoaminoxidase/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Síndrome da Serotonina/fisiopatologia , Adulto , Eletrocardiografia , Serviços Médicos de Emergência , Evolução Fatal , Feminino , Humanos , Suicídio
14.
Anaesthesist ; 55(2): 179-84, 2006 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-16308710

RESUMO

Anaesthesia and emergency medical care for infants and toddlers is often associated with high clinical demands and specific challenges. Nevertheless, a significant proportion of interventions is performed by anaesthetists and emergency physicians with no specialised paediatric training and little experience in the management of anaesthetic incidents and emergencies specific to these age groups. Extensive studies have demonstrated a close inverse correlation between the level of specialisation and perioperative morbidity and mortality. However, clinical circumstances and the relatively small number of paediatric cases at many institutions often hinder the establishment of improved training concepts. Recently, high-fidelity infant simulators have become available, which permit authentic exposure to a large spectrum of scenarios in paediatric anaesthesia and emergency medicine. A multimodular concept of training, including such simulator-based techniques, may relieve the widespread shortage in clinical experience, and hence greatly facilitate improvement of quality of care and patient safety.


Assuntos
Anestesiologia/educação , Medicina de Emergência/educação , Manequins , Pediatria/educação , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido
15.
Artigo em Alemão | MEDLINE | ID: mdl-16145642

RESUMO

OBJECTIVE: On October 1 (st) 2003 Emergency Medicine was recognised for the first time as an independent cross section speciality in the new German "Approbationsordnung fuer Aerzte" (Medical Licensing Regulations). These amendments were made not only to increase the amount of small group teaching sessions but also to encourage a multidisciplinary and rather practical approach to the related topics. This article portrays the realisation of these objectives in form of a multidisciplinary module, as it has been established at University of Göttingen Medical School since the summer semester of 2004. We present the new curriculum, calculate the associated personnel resources and demonstrate the results of the structured evaluation given by the participating students. METHODS: We linked the fields of emergency and intensive care medicine by splitting them up into submodules which the students had to run through according to a set rota. 162 students were allocated to 27 small groups. Every student received a total of 38.5 hours of teaching, with the workshops coming to 46.8 %. The workshops comprised of nine sessions, three in Emergency Medicine, four in Intensive Care Medicine and two at human patient simulators. In addition we scheduled a seminar and an accompanying lecture. The final examination was performed as an Objective Structured Clinical Evaluation (OSCE). RESULTS: The realisation of the new module required a total of 1290 working hours for medical staff and 130 for our student aids. Compared to all other modules of Goettingen University Medical School the module here presented obtained the highest overall evaluation score by the medical students. Lessons with a high amount of practical involvement (i. e. Emergency Medicine and simulator-based workshops) were significantly better evaluated than rather formal teaching techniques, such as the lectures and the seminar. According to the students' self-assessment the simulator-based workshops were seen particularly valuable for the facilitation of knowledge transfer into clinical practice. CONCLUSION: The determined realisation of the new German Medical Licensing Regulations requires considerable time resources. However, its evaluation by the medical students is strikingly positive.


Assuntos
Anestesiologia/educação , Cuidados Críticos , Educação de Graduação em Medicina/tendências , Medicina de Emergência/educação , Especialização/tendências , Anestesiologia/legislação & jurisprudência , Currículo , Educação de Graduação em Medicina/legislação & jurisprudência , Medicina de Emergência/legislação & jurisprudência , Alemanha , Manequins , Especialização/legislação & jurisprudência , Estudantes de Medicina
16.
Anaesthesist ; 54(6): 582-7, 2005 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-15812620

RESUMO

Despite the development of new devices and strategies to manage and secure the difficult airway, morbidity and mortality in anaesthesia due to airway problems such as difficult intubation or unrecognised failed intubation remain high. The problem seems to lie in the transfer of skills and strategies to daily clinical practice. Common methods for airway management training include theoretical instructions and hands-on sessions with manikins, animal models and cadavers. Simulation provides the opportunity to train skills and resolve specific situations embedded in a realistic scenario, facilitate the transfer of cognitive, psychomotor and affective abilities into daily clinical practice and help to improve behaviour in critical situations. This article outlines new training concepts in airway management with the help of simulation and simulators. We describe technical prerequisites and provide information on the implementation of difficult airway scenarios.


Assuntos
Anestesiologia/educação , Manequins , Animais , Recursos Audiovisuais , Competência Clínica , Humanos
17.
J Nerv Ment Dis ; 193(2): 131-5, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15684916

RESUMO

The present study was designed to create a group of scales from the items on the Symptom Checklist 90 (SCL-90) to identify common psychiatric diagnoses. Subjects were 1457 adult psychiatric outpatients who completed the Symptom Checklist-90 and a structured diagnostic interview at the time of their initial evaluation. A combination of rational and empirical test construction methods was used to create the SCL-90 Diagnostic Scales, item sets that identify eight common psychiatric conditions: major depression, bipolar disorder, schizophrenia, antisocial personality disorder, somatization disorder, obsessive-compulsive disorder, panic disorder, and agoraphobia. These specially constructed scales were found to possess good internal reliability. These scales were also shown to differentiate patients positive for each of the eight psychiatric disorders from other psychiatric patients who did not have that disorder. Sensitivities and specificities are reported for each item set. In addition to their utility at the time of initial assessment as an aid in identifying diagnosis, the SCL-90 Diagnostic Scales may have other potential uses, such as in monitoring the symptom course of the patient's disorder or disorders over time.


Assuntos
Transtornos Mentais/diagnóstico , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Assistência Ambulatorial , Transtorno da Personalidade Antissocial/diagnóstico , Transtorno da Personalidade Antissocial/epidemiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Humanos , Kansas/epidemiologia , Programas de Rastreamento/métodos , Transtornos Mentais/epidemiologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/epidemiologia , Transtornos Fóbicos/diagnóstico , Transtornos Fóbicos/epidemiologia , Prevalência , Psicometria/métodos , Reprodutibilidade dos Testes , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Sensibilidade e Especificidade , Transtornos Somatoformes/diagnóstico , Transtornos Somatoformes/epidemiologia
18.
Acta Psychiatr Scand ; 110(6): 476-82, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15521834

RESUMO

OBJECTIVE: This prospective high-risk study examined the influence of father's alcoholism and other archival-generated measures on premature death. METHOD: Sons of alcoholic fathers (n = 223) and sons of non-alcoholic fathers (n = 106) have been studied from birth to age 40. Archival predictors of premature death included father's alcoholism, childhood developmental data, and diagnostic information obtained from the Psychiatric Register and alcoholism clinics. RESULTS: By age 40, 21 of the 329 subjects had died (6.4%), a rate that is more than two times greater than expected. Sons of alcoholic fathers were not more likely to die by age 40. Premature death was associated with physical immaturity at 1-year of age and psychiatric/alcoholism treatment. No significant interactions were found between risk and archival measures. CONCLUSION: Genetic vulnerability did not independently predict death at age 40. Death was associated with developmental immaturities and treatment for a psychiatric and/or substance abuse problem.


Assuntos
Fatores Etários , Alcoolismo/genética , Alcoolismo/mortalidade , Causas de Morte , Pai , Adulto , Alcoolismo/epidemiologia , Criança , Dinamarca/epidemiologia , Pai/estatística & dados numéricos , Previsões , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Sistema de Registros , Fatores de Risco , Assunção de Riscos , Análise de Sobrevida
19.
Crit Care Nurs Clin North Am ; 13(2): 207-19, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11866403

RESUMO

Morphine is the preferred analgesic agent for the critically ill patient. Fentanyl is the preferred analgesic agent for critically ill patients with hemodynamic instability or for patients manifesting symptoms of histamine release with morphine or morphine allergy. Hydromorphone is an acceptable alternative to morphine for patients with significant adverse affects from morphine or severe renal dysfunction. Meperidine and intravenous codeine should be avoided if at all possible. APAP and NSAIDs may be useful in the management of acute pain secondary to their opioid-sparing effects. Use of nonopioid analgesics may reduce the dose of opioid required for adequate pain control and help to minimize opioid-induced side effects. NSAIDs should be used only when the benefit-to-risk ratio is favorable. APAP should be used as an adjunct but not as the sole analgesic agent in critically ill patients. Regardless of which agent or agents are used to optimize pain control, it is imperative that caregivers recognize that the optimal analgesic dose and regimen vary widely between patients. Based on the pharmacokinetics and pharmacodynamics of the agent(s) selected, enough time for an adequate trial should be allowed before switching to other agents. Employing these principles optimizes the use of medications in the management of the complex physiologic response to pain.


Assuntos
Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Algoritmos , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/farmacocinética , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacocinética , Disponibilidade Biológica , Vias de Administração de Medicamentos , Humanos
20.
Shock ; 14(3): 347-53, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11028555

RESUMO

Studies have shown that immune responses are depressed in male mice, but not in proestrus females after trauma-hemorrhage (TH), resulting in increased mortality from subsequent sepsis in male mice compared with female mice. These gender-specific alterations in immune function are believed to be due to differences in sex steroid levels. Aromatase is a key enzyme in the sex steroid biosynthesis. Although earlier studies have shown that aromatase inhibitors prevent thymic atrophy in aged male rats, it remains unknown whether the use of 4-hydroxy-androstenedione (4-OHA) after TH in male mice has any salutary effects on the depressed immune responses. Male C3H/HeN mice were sham operated or subjected to trauma (i.e., midline laparotomy) and hemorrhagic shock (30+/-5 mmHg for 90 min) followed by adequate fluid resuscitation. 4-OHA (5 mg/kg) or vehicle was administrated s.c. just before resuscitation. At 2 h after resuscitation, the mice were killed, and spleens were harvested. Splenocyte proliferation, interleukin (IL-2), interferon (IFN-gamma), and IL-10 release and expression of androgen (AR) and estrogen receptors (ER)-alpha and -beta by immunoblot and reverse transcription-polymerase chain reaction (RT-PCR) were assessed. In another group, sepsis was induced by cecal ligation and puncture (CLP) 3 days after resuscitation, and survival was measured over a period of 10 days. A significant decrease in splenocyte proliferation, IL-2, and IFN-gamma release and increased release of IL-10 were observed in vehicle-treated mice. Animals treated with 4-OHA showed increased splenocyte proliferation, IL-2, and IFN-gamma release, and decreased IL-10 release. Immunoblot analysis showed decreased expression of the cytosolic AR, but no significant difference in the cytosolic and nuclear ER-alpha and -beta expression was observed in the vehicle-treated group after TH. In addition, AR and ER-beta mRNA expression was increased, whereas ER-alpha expression decreased in the vehicle-treated group after TH. ER-alpha expression decreased and ER-beta expression increased in the nucleus of 4-OHA treated mice as determined by immunoblot. There was no difference in the cytosolic AR expression in the 4-OHA-treated group after TH. AR and ER-beta mRNA expression was unaffected, whereas ER-alpha expression increased under such conditions. In additional groups, the increased mortality rate after TH and subsequent sepsis was significantly reduced by 4-OHA treatment. Thus, 4-OHA seems to be a novel and useful adjunct for restoring the depressed immune functions in males after TH and for decreasing mortality rates from subsequent sepsis.


Assuntos
Androstenodiona/análogos & derivados , Inibidores Enzimáticos/uso terapêutico , Sepse/mortalidade , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/imunologia , Ferimentos e Lesões/imunologia , Androstenodiona/uso terapêutico , Animais , Inibidores da Aromatase , Citocinas/metabolismo , Receptor alfa de Estrogênio , Receptor beta de Estrogênio , Masculino , Camundongos , Camundongos Endogâmicos C3H , Receptores Androgênicos/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Estrogênio/genética , Ressuscitação , Sepse/complicações , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Taxa de Sobrevida , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Ferimentos e Lesões/complicações , Ferimentos e Lesões/tratamento farmacológico
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