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BACKGROUND: Swallow or deglutition syncope is an unusual type of neurally-mediated syncope associated with life-threatening bradyarrhythmia and hypotension. It is a difficult condition to diagnose with commonly delayed diagnosis and management. There is lack of review articles that elucidate the basic demographics, clinical characteristics and management of this rare condition. This publication systematically reviews the 101 case reports published since 1793 on swallow syncope. CASE PRESENTATION: A 59-year-old man presented with the complaint of recurrent dizziness associated with meals. A 24-h ambulatory ECG recording confirmed an episode of p-wave asystole at the time of food intake. Oesophagogastroduodenoscopy with balloon inflation in the mid to lower oesophagus resulted in a 5.6 s sinus pause. The patient's symptoms resolved completely following insertion of a permanent dual chamber pacemaker. CONCLUSIONS: Swallow syncope is extremely rare, but still needs to be considered during diagnostic workup. It is commonly associated with gastro-intestinal disease. Permanent pacemaker implantation is the first line treatment.
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Deglución , Ingestión de Alimentos , Síncope/etiología , Presión Sanguínea , Estimulación Cardíaca Artificial , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Marcapaso Artificial , Síncope/diagnóstico , Síncope/fisiopatología , Síncope/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: Staphylococcus has replaced streptococcus as the most common cause of infective endocarditis (IE) in developed health care systems. The trend in developing countries is less clear. AIM: To examine the epidemiological trends of infective endocarditis in a developing nation. METHODS: Single-centre, retrospective study of patients admitted with IE to a tertiary hospital in Malaysia over a 12-year period. RESULTS: The analysis included 182 patients (n = 153 Duke's definite IE, n = 29 possible IE). The mean age was 51 years. Rheumatic heart disease was present in 42%, while 7.6% were immunocompromised. IE affected native valves in 171 (94%) cases. Health-care associated IE (HCAIE) was recorded in 68 (37.4%). IE admission rates increased from 25/100,000 admissions (2012) to 59/100,000 admissions (2017). At least one major complication on admission was detected in 59 (32.4%) patients. Left-sided IE was more common than right-sided IE [n = 159 (87.4%) vs. n = 18 (9.9%)]. Pathogens identified by blood culture were staphylococcus group [n = 58 (40.8%)], streptococcus group [n = 51 (35.9%)] and Enterococcus species [n = 13 (9.2%)]. staphylococcus infection was highest in the HCAIE group. In-hospital death occurred in 65 (35.7%) patients. In-hospital surgery was performed for 36 (19.8%) patients. At least one complication was documented in 163 (85.7%). CONCLUSION: Staphylococcus is the new etiologic champion, reflecting the transition of the healthcare system. Streptococcus is still an important culprit organism. The incidence rate of IE appears to be increasing. The rate of patients with underlying rheumatic heart disease is still high.
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Endocarditis Bacteriana , Staphylococcus aureus/aislamiento & purificación , Adulto , Anciano , Antibacterianos/uso terapéutico , Infección Hospitalaria , Países en Desarrollo , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/mortalidad , Femenino , Humanos , Malasia/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Infecciones Estafilocócicas/microbiología , Streptococcus/aislamiento & purificación , Adulto JovenRESUMEN
OBJECTIVES: The aim of this study was to evaluate if emergency medicine trainees with a short duration of training in echocardiography could perform and interpret bedside-focused echocardiography reliably on emergency department patients. METHODS: Following a web-based learning module and 3â h of proctored practical training, emergency medicine trainees were evaluated in technical and interpretative skills in estimating left ventricular function, detection of pericardial effusion and inferior vena cava (IVC) diameter measurements using bedside-focused echocardiography on emergency department patients. An inter-rater agreement analysis was performed between the trainees and a board-certified cardiologist. RESULTS: 100 focused echocardiography examinations were performed by nine emergency medicine trainees. Agreement between the trainees and the cardiologist was 93% (K=0.79, 95% CI 0.773 to 0.842) for visual estimation of left ventricular function, 92.9% (K=0.80, 95% CI 0.636 to 0.882) for quantitative left ventricular ejection fraction by M-mode measurements, 98% (K=0.74, 95% CI 0.396 to 1.000) for the detection of pericardial effusion, and 64.2% (K=0.45, 95% CI 0.383 to 0.467) for IVC diameter assessment. The Bland-Altman limits of agreement for left ventricular function was -9.5% to 13.7%, and a Pearson's correlation yielded a value of 0.82 (p<0.0001, 95% CI 0.734 to 0.881). The trainees detected pericardial effusion with a sensitivity of 60%, specificity of 100%, positive predictive value of 100% and negative predictive value of 97.9%. CONCLUSIONS: Emergency medicine trainees were found to be able to perform and interpret focused echocardiography reliably after a short duration of training.
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Competencia Clínica , Instrucción por Computador , Ecocardiografía , Educación a Distancia , Medicina de Emergencia/educación , Sistemas de Atención de Punto , Curriculum , Humanos , Malasia , Derrame Pericárdico/diagnóstico por imagen , Estudios Prospectivos , Volumen Sistólico , Vena Cava Inferior/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
Pseudoaneurysms of the aortic root are rare. A case of prosthetic aortic valve infection progressing from a confined intramural abscess to a ruptured abscess communicating with the aorta and forming a large pseudoaneurysm is described. Additionally, data from all cases and case series, published between 2000 and 2021, was analyzed. A PUBMED search for the keywords "aortic root mycotic aneurysm," "aortic root abscess AND infective endocarditis," and "aortic root mycotic aneurysm AND infective endocarditis" yielded 152 publications (with 157 cases described): Aortic pseudoaneurysm is more common in males (80.9%, n = 127). Mean age is 51 years (4 months-84 years). The most common symptom is fever (68.5%, n = 102). Mean time until diagnosis is 27.2 days. Embolic complications are present in 17.8% (n = 28) at diagnosis. Most cases are due to valvular infections (n = 72 cases, 45.9%). Prior cardiac surgery is documented in 49.0% (n = 77). The mean time interval for developing aortic root abscess following heart surgery is 32.2 months. 22.3% (n = 35) are immunocompromised. Aetiological agents were Staphylococcus sp. (34.1%, n = 47) and Streptococcus sp. (23.2%, n = 32). Mean antimicrobial therapy lasts 58.5 days. Outcome with surgery is superior to medical treatment: overall inpatient mortality 18.5% (n = 27); with surgery 12.2% (n = 15 out of 123 patients), with only medical management 47.8% (n = 11 out of 23 patients). In conclusion, aortic root pseudoaneurysm occurs most commonly in middle-aged male patients. History of prior aortic procedures is commonly present. Correct diagnosis hinges on detailed history, transoesophageal echocardiography, and computed tomography (CT) aorta. Surgery is the preferred therapeutic option. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01580-x.
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AIMS: Heart failure (HF) is a growing health problem, yet there are limited data on patients with HF in Malaysia. The Malaysian Heart Failure (MY-HF) Registry aims to gain insights into the epidemiology, aetiology, management, and outcome of Malaysian patients with HF and identify areas for improvement within the national HF services. METHODS AND RESULTS: The MY-HF Registry is a 3-year prospective, observational study comprising 2717 Malaysian patients admitted for acute HF. We report the description of baseline data at admission and outcomes of index hospitalization of these patients. The mean age was 60.2 ± 13.6 years, 66.8% were male, and 34.3% had de novo HF. Collectively, 55.7% of patients presented with New York Heart Association (NYHA) Class III or IV; ischaemic heart disease was the most frequent aetiology (63.2%). Most admissions (87.3%) occurred via the emergency department, with 13.7% of patients requiring intensive care, and of these, 21.8% needed intubation. The proportion of patients receiving guideline-directed medical therapy increased at discharge (84.2% vs. 93.6%). The median length of stay (LOS) was 5 days, and in-hospital mortality was 2.9%. Predictors of LOS and/or in-hospital mortality were age, NYHA class, estimated glomerular filtration rate, and comorbid anaemia. LOS and in-hospital mortality were similar regardless of ejection fraction. CONCLUSIONS: The MY-HF Registry showed that the HF population in Malaysia is younger, predominantly male, and ischaemic-driven and has good prospects with hospitalization for optimization of treatment. These findings suggest a need to reassess current clinical practice and guide resource allocation to improve patient outcomes.
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Insuficiencia Cardíaca , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Estudios Prospectivos , Tiempo de Internación , Sistema de Registros , Insuficiencia Cardíaca/terapiaRESUMEN
The rate of organ donations from deceased donors in Malaysia is among the lowest in the world. This may be because of the passivity among health professionals in approaching families of potential donors. A questionnaire-based study was conducted amongst health professionals in two tertiary hospitals in Kuala Lumpur, Malaysia. Four hundred and sixty-two questionnaires were completed. 93.3% of health professionals acknowledged a need for organ transplantation in Malaysia. 47.8% were willing to donate their organs (with ethnic and religious differences). Factors which may be influencing the shortage of organs from deceased donors include: nonrecognition of brainstem death (38.5%), no knowledge on how to contact the Organ Transplant Coordinator (82.3%), and never approaching families of a potential donor (63.9%). There was a general attitude of passivity in approaching families of potential donors and activating transplant teams among many of the health professionals. A misunderstanding of brainstem death and its definition hinder identification of a potential donor. Continuing medical education and highlighting the role of the Organ Transplant Coordinator, as well as increasing awareness of the public through religion and the media were identified as essential in improving the rate of organ donations from deceased donors in Malaysia.
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Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Adolescente , Adulto , Cadáver , Estudios Transversales , Etnicidad , Femenino , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , Malasia , Masculino , Persona de Mediana Edad , Trasplante de Órganos , Religión , Encuestas y Cuestionarios , Donantes de Tejidos/estadística & datos numéricos , Adulto JovenRESUMEN
INTRODUCTION: Achieving target door-needle times for ST elevation myocardial infarction remains challenging. Data on emergency department (ED) doctor-led thrombolysis in developing countries and factors causing delay are limited. OBJECTIVES: To assess the effect on door-needle times by transferring responsibility for thrombolysis to the ED doctors and to identify predictors of prolonged door-needle times. METHODOLOGY: Data on medical on-call team-led thrombolysis at a tertiary Asian hospital were prospectively collected from May 2007 to Aug 2008 (1st study period). In September 2008, ED doctors were empowered to perform thrombolysis. The practice change was accompanied by new guidelines, tick chart implementation, and training sessions. Data were then consecutively collected from September 2008 to May 2009 (2nd study period). Door-to-needle times for the 1st and 2nd study periods were compared. All cases were analysed for factors of delay by multiple logistic regression. RESULTS: 297 patients were thrombolysed, 169 by the medical on-call team during the 1st study period and 128 by the ED doctors during the 2nd study period. Median door-needle times were 54 and 48 min, respectively (p=0.76). Significant delays were predicted by 'incorrect initial ECG interpretation' (adjusted OR (aOR) 14.3), 'inappropriate triage' (aOR 10.4) and 'multiple referrals' (aOR 5.9). No cases of inappropriate thrombolysis were recorded. CONCLUSIONS: Transfer of responsibility for thrombolysis to the ED doctors did not improve door-needle times despite measures introduced to facilitate this change. Key causative factors for this failure were identified.
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Servicios Médicos de Urgencia/normas , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea/normas , Terapia Trombolítica , Tiempo de Tratamiento , Triaje/normas , Adulto , Anciano , Anciano de 80 o más Años , Toma de Decisiones , Países en Desarrollo , Femenino , Adhesión a Directriz , Humanos , Malasia/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Admisión del Paciente , Proyectos Piloto , Guías de Práctica Clínica como Asunto , Indicadores de Calidad de la Atención de Salud , Terapia Trombolítica/normas , Tiempo de Tratamiento/normas , Resultado del TratamientoRESUMEN
Endoscopic ultrasonography-guided transesophageal pericardiocentesis was performed for a posteriorly located effusion not amenable to transthoracic drainage in a 58-year-old woman with a history of recurrent breast adenocarcinoma who presented with dyspnea. The patient had a pericardial effusion that resulted in cardiac tamponade. Transthoracic pericardiocentesis was unsuitable because of the posterior location of the effusion. Pericardiocentesis via the transesophageal route was performed. The pericardial sac was punctured with a 19-gauge needle, and 245 mL of pericardial fluid were aspirated, resulting in the resolution of the tamponade physiology. Endoscopic ultrasonography-guided transesophageal drainage is a novel and promising therapeutic option for posteriorly located pericardial effusions.
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Taponamiento Cardíaco , Derrame Pericárdico , Femenino , Humanos , Persona de Mediana Edad , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/etiología , Derrame Pericárdico/terapia , Pericardiocentesis/métodos , Taponamiento Cardíaco/diagnóstico , Taponamiento Cardíaco/etiología , Taponamiento Cardíaco/cirugía , Pericardio , Agujas/efectos adversosRESUMEN
Leucine-rich α2-glycoprotein (LRG1) mediates cardiac fibrocyte activation. It is upregulated in inflammatory conditions, atherosclerosis, and fibrosis. Diastolic dysfunction (DD) is due to myocardial fibrosis. This cross-sectional study examined the relationship between LRG1 and DD. Patients with symptoms of chronic coronary ischemia were recruited. Patients with symptoms of overt heart failure, ejection fraction (EF) < 55%, impaired renal function, infection, and recent trauma were excluded from the study. Clinical parameters examined were SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score, echocardiographic assessment, and LRG1 levels. Binary stepwise logistic regression was used to evaluate the association between LRG1 and DD. Receiver Operating Characteristic (ROC) analysis was used to determine optimal cut-off values and predictive performance of LRG1. A total of 94 patients were enrolled in the study, with 47 having a clinical diagnosis of DD. Plasma LRG1 was significantly (U = 417.00, p < 0.001) higher in the DD group (M = 14) compared to the No-DD group (M = 8) by Mann-Whitney U test. There were higher SYNTAX scores in the DD group (M = 24.5) compared with No-DD (M = 7). LRG1 had significant predictability of DD (OR = 1.32 (95% CI: 1.14-1.53)). The ROC showed an AUC = 0.89 (95% CI: 0.82-0.95). LRG1 had a 78% sensitivity (95% CI: 65.3-87.7) and 72.3% specificity (95% CI: 57.4-84.4) for predicting DD at a cut-off value of "9". In conclusion, we identified LRG1 as a novel independent predictor of DD. Further studies are warranted to validate the utility of LRG1 in predicting DD.
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Introduction: Ventricular remodeling is a mal-adaptive process. Both angiotensin-converting enzyme inhibitors and sacubitril/valsartan have been shown to reverse remodeling in mostly uncontrolled observational studies. There is a lack of head-to-head studies. Methods: This cohort study compares the remodeling effects of angiotensin receptor blockers combined with a neprilysin inhibitor (ARNI) and perindopril in heart failure with reduced ejection fraction (HFrEF) patients between January 2017 and December 2020. Inclusion criteria: (i) age > 18 years, (ii) recent diagnosis of de-novo HFrEF (EF < 40%), (iii) baseline echocardiography performed not more than 2 months prior to treatment onset, and (iv) follow-up echocardiography performed not earlier than 6 months and not later than 18 months posttreatment onset. No prior treatment with renin-angiotensin-aldosterone system inhibitors was permitted in the ARNI group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were analyzed. A two-way repeated measure ANOVA (for normally distributed) and generalized estimating equation test for nonnormally distributed interval dependent variables. Mean comparison between and within groups was performed using the Bonferroni test. Results: Following an average treatment period of 9 months, LVEF improved from 24.9% to 36.4% for ARNI and from 28.7% to 40.5% for perindopril, increments of 11.5% and 11.8% resp. (Bonferroni test [P ≤ .05]). LVEDV was reduced by 8.4â mL and 3.2â mL, and LVESV by 17.9â mL and 10.8â mL for ARNI and perindopril resp. Only the reduction of LVESV for ARNI was statistically significant (P = .007). Conclusion: Both ARNI and perindopril yielded a significant improvement in the LVEF within 9 months. The remodeling effect of ARNI seems stronger because of the greater improvements in left ventricular volumes.
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Insuficiencia Cardíaca , Humanos , Adulto , Persona de Mediana Edad , Volumen Sistólico , Estudios de Cohortes , Perindopril/efectos adversos , Función Ventricular Izquierda , Tetrazoles/farmacología , Resultado del Tratamiento , Valsartán/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Combinación de MedicamentosAsunto(s)
Enfermedades de los Trabajadores Agrícolas/diagnóstico , Cardiomiopatía Restrictiva/diagnóstico , Síndrome Hipereosinofílico/diagnóstico , Estrongiloidiasis/diagnóstico , Animales , Cardiomiopatía Restrictiva/parasitología , Insuficiencia Cardíaca/parasitología , Humanos , Síndrome Hipereosinofílico/parasitología , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Strongyloides stercoralis , Trombosis/diagnóstico , Trombosis/parasitologíaRESUMEN
Cardiomyopathy (CMP) constitutes a diverse group of myocardium diseases affecting the pumping ability of the heart. Genetic predisposition is among the major factors affecting the development of CMP. Globally, there are over 100 genes in autosomal and mitochondrial DNA (mtDNA) that have been reported to be associated with the pathogenesis of CMP. However, most of the genetic studies have been conducted in Western countries, with limited data being available for the Asian population. Therefore, this study aims to investigate the mutation spectrum in the mitochondrial genome of 145 CMP patients in Malaysia. Long-range PCR was employed to amplify the entire mtDNA, and whole mitochondrial genome sequencing was conducted on the MiSeq platform. Raw data was quality checked, mapped, and aligned to the revised Cambridge Reference Sequence (rCRS). Variants were named, annotated, and filtered. The sequencing revealed 1,077 variants, including 18 novel and 17 CMP and/or mitochondrial disease-associated variants after filtering. In-silico predictions suggested that three of the novel variants (m.8573G>C, m.11916T>A and m.11918T>G) in this study are potentially pathogenic. Two confirmed pathogenic variants (m.1555A>G and m.11778G>A) were also found in the CMP patients. The findings of this study shed light on the distribution of mitochondrial mutations in Malaysian CMP patients. Further functional studies are required to elucidate the role of these variants in the development of CMP.
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Cardiomiopatías , Genoma Mitocondrial , Humanos , Genoma Mitocondrial/genética , Mitocondrias/genética , Mutación/genética , ADN Mitocondrial/genética , Cardiomiopatías/genéticaAsunto(s)
Cardiomegalia/diagnóstico , Prótesis Valvulares Cardíacas , Válvula Mitral , Anciano , Tos/etiología , Disnea/etiología , Ecocardiografía , Femenino , Atrios Cardíacos , Humanos , Angiografía por Resonancia Magnética , Insuficiencia de la Válvula Mitral/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiologíaRESUMEN
For bone repair, transplantation of periosteal progenitor cells (PCs), which had been amplified within supportive scaffolds, is applied clinically. More innovative bone tissue engineering approaches focus on the in situ recruitment of stem and progenitor cells to defective sites and their subsequent use for guided tissue repair. Chemokines are known to induce the directed migration of bone marrow CD34(-) mesenchymal stem cells (MSCs). The aim of our study was to determine the chemokine receptor expression profile of human CD34(-) PCs and to demonstrate that these cells migrate upon stimulation with selected chemokines. PCs were isolated from periosteum of the mastoid bone and displayed a homogenous cell population presenting an MSC-related cell-surface antigen profile (ALCAM(+), SH2(+), SH3(+), CD14(-), CD34(-), CD44(+), CD45(-), CD90(+)). The expression profile of chemokine receptors was determined by real-time PCR and immunohistochemistry. Both methods consistently demonstrated that PCs express receptors of all four chemokine subfamilies CC, CXC, CX(3)C, and C. Migration of PCs and a dose-dependent migratory effect of the chemokines CCL2 (MCP1), CCL25 (TECK), CXCL8 (IL8), CXCL12 (SDF1alpha), and CXCL13 (BCA1), but not CCL22 (MDC) were demonstrated using a 96-multiwell chemotaxis assay. In conclusion, for the first time, here we report that human PCs express chemokine receptors, present their profile, and demonstrate a dose-dependent migratory effect of distinct chemokines on these cells. These results are promising towards in situ bone repair therapies based on guiding PCs to bone defects, and encourage further in vivo studies.
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Células Madre Adultas/inmunología , Movimiento Celular , Quimiocinas CC/metabolismo , Quimiocinas CXC/metabolismo , Apófisis Mastoides/inmunología , Periostio/inmunología , Receptores de Quimiocina/metabolismo , Adulto , Antígenos CD/análisis , Separación Celular , Células Cultivadas , Quimiocina CCL2/metabolismo , Quimiocina CXCL12/metabolismo , Quimiocina CXCL13/metabolismo , Relación Dosis-Respuesta Inmunológica , Citometría de Flujo , Perfilación de la Expresión Génica/métodos , Humanos , Inmunohistoquímica , Interleucina-8/metabolismo , Apófisis Mastoides/citología , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Periostio/citología , Reacción en Cadena de la Polimerasa , Receptores de Quimiocina/genéticaRESUMEN
Although changes of cerebral blood flow (CBF) in and around traumatic contusions are well documented, the role of CBF for the delayed death of neuronal cells in the traumatic penumbra ultimately resulting in secondary contusion expansion remains unclear. The aim of the current study was therefore to investigate the relationship between changes of CBF and progressive peri-contusional cell death following traumatic brain injury (TBI). CBF and contusion size were measured in C57Bl6 mice under continuous on-line monitoring of (ETp)CO2 before, and at 15 min and 24 h following controlled cortical impact by 14C-iodoantipyrine autoradiography (IAP-AR; n = 5-6 per group) and by Nissl staining, respectively. Contused and ischemic (CBF < 10%) tissue volumes were calculated and compared over time. Cortical CBF in not injured mice varied between 69 and 93 mL/100mg/min depending on the anatomical location. Fifteen minutes after trauma, CBF decreased in the whole brain by approximately 50% (39 +/- 18 mL/100mg/min; p < 0.05), except in contused tissue where it fell by more than 90% (3 +/- 2 mL/100mg/min; p < 0.001). Within 24 h after TBI, CBF recovered to normal values in all brain areas except the contusion where it remained reduced by more than 90% (p < 0.001). Contusion volume expanded from 24.9 to 35.5 mm3 (p < 0.01) from 15 min to 24 h after trauma (+43%), whereas the area of severe ischemia (CBF < 10%) showed only a minimal (+13%) and not significant increase (22.3 to 25.1 mm3). The current data therefore suggest that the delayed secondary expansion of a cortical contusion following traumatic brain injury may not be caused by a reduction of CBF alone.
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Antipirina/análogos & derivados , Autorradiografía/métodos , Lesiones Encefálicas/diagnóstico por imagen , Lesiones Encefálicas/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Circulación Cerebrovascular , Animales , Antiinflamatorios no Esteroideos , Biomarcadores , Encéfalo/irrigación sanguínea , Infarto Encefálico/diagnóstico por imagen , Infarto Encefálico/fisiopatología , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/fisiopatología , Radioisótopos de Carbono , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/fisiopatología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Flujometría por Láser-Doppler , Masculino , Ratones , Ratones Endogámicos C57BL , Microcirculación/diagnóstico por imagen , Microcirculación/fisiopatología , Degeneración Nerviosa/diagnóstico por imagen , Degeneración Nerviosa/etiología , Degeneración Nerviosa/fisiopatología , Cintigrafía , Recuperación de la Función , Coloración y Etiquetado , Factores de TiempoRESUMEN
The reconstruction of extensive tracheal defects is still an unsolved challenge for thoracic surgery. Tissue engineering is a promising possibility to solve this problem through the generation of an autologous tracheal replacement from patients' own tissue. Therefore, this study investigated the potential of three different coculture systems, combining human respiratory epithelial cells and human chondrocytes. The coculture systems were analyzed by histological staining with alcian blue, immunohistochemical staining with the antibodies, 34betaE12 and CD44v6, and scanning electron microscopy. The first composite culture consisted of human respiratory epithelial cells seeded on human high-density chondrocyte pellets. For the second system, we used native articular cartilage chips as base for the respiratory epithelial cells. The third system consisted of a collagen membrane, seeded with respiratory epithelial cells and human chondrocytes onto different sides of the membrane, which achieved the most promising results. In combination with an air-liquid interface system and fibroblast-conditioned medium, an extended epithelial multilayer with differentiated epithelial cells could be generated. Our results suggest that at least three factors are necessary for the development towards a tracheal replacement: (1) a basal lamina equivalent, consisting of collagen fibers for cell-cell interaction and cell polarization, (2) extracellular factors of mesenchymal fibroblasts, and (3) the presence of an air-liquid interface system for proliferation and differentiation of the epithelial cells.