RESUMEN

OBJECTIVES: To determine the clinical characteristics and outcomes of culture-negative septic shock in comparison with culture-positive septic shock. DESIGN: Retrospective nested cohort study. SETTING: ICUs of 28 academic and community hospitals in three countries between 1997 and 2010. SUBJECTS: Patients with culture-negative septic shock and culture-positive septic shock derived from a trinational (n = 8,670) database of patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with culture-negative septic shock (n = 2,651; 30.6%) and culture-positive septic shock (n = 6,019; 69.4%) were identified. Culture-negative septic shock compared with culture-positive septic shock patients experienced similar ICU survival (58.3% vs 59.5%; p = 0.276) and overall hospital survival (47.3% vs 47.1%; p = 0.976). Severity of illness was similar between culture-negative septic shock and culture-positive septic shock groups ([mean and SD Acute Physiology and Chronic Health Evaluation II, 25.7 ± 8.3 vs 25.7 ± 8.1]; p = 0.723) as were serum lactate levels (3.0 [interquartile range, 1.7-6.1] vs 3.2 mmol/L [interquartile range, 1.8-5.9 mmol/L]; p = 0.366). As delays in the administration of appropriate antimicrobial therapy after the onset of hypotension increased, patients in both groups experienced congruent increases in overall hospital mortality: culture-negative septic shock (odds ratio, 1.56; 95% CI [1.47-1.66]; p < 0.0001) and culture-positive septic shock (odds ratio, 1.65; 95% CI [1.59-1.71]; p < 0.0001). CONCLUSIONS: Patients with culture-negative septic shock behave similarly to those with culture-positive septic shock in nearly all respects; early appropriate antimicrobial therapy appears to improve mortality. Early recognition and eradication of infection is the most obvious effective strategy to improve hospital survival.

Asunto(s)

Mortalidad Hospitalaria/tendencias , Unidades de Cuidados Intensivos/estadística & datos numéricos , Choque Séptico/mortalidad , Tiempo de Tratamiento/estadística & datos numéricos , APACHE , Anciano , Antibacterianos/administración & dosificación , Cultivo de Sangre , Temperatura Corporal , Comorbilidad , Femenino , Frecuencia Cardíaca , Humanos , Hipotensión/etiología , Hipotensión/terapia , Ácido Láctico/sangre , Masculino , Persona de Mediana Edad , Respiración Artificial , Estudios Retrospectivos , Choque Séptico/complicaciones , Factores de Tiempo

RESUMEN

Tuberous sclerosis complex (TSC) or Bourneville disease is a rare autosomal dominant neurocutaneous disorder that affects various organs. Pulmonary involvement in TSC may consist of lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH), occurring together or alone. In patients with TSC-LAM, chylous pleural effusion (CPE) is a rare, though well-recognized, complication with an unpredictable clinical course. In refractory or persistent CPE, optimal management remains a clinical challenge. We report the unique case of a 29-year-old Caucasian female, neversmoker, with definite TSC since infancy, characterized by seizures, facial angiofibromas ("adenoma sebaceum"), bilateral renal angiomyolipomas, hepatic angiomyolipomas, subcortical/cortical tubers, and subependymal nodules. At 27 years old, due to bleeding from the renal angiomyolipomas, she underwent nephrectomy, first of the right, and then a year and 9 months later, of the left kidney. She was hemodialysis dependent for the next five years until cadaveric kidney transplantation. The medical history was also remarkable for recurrent exudative lymphocytic PE despite repeated therapeutic thoracenteses, with first presentation at 23.5 years of age. Chylothorax was initially diagnosed at 24 years and 8 months old (PE triglycerides 4.53 mmol/L), and reconfirmed at age 29 (PE triglycerides 12.46-15.30 mmol/L). Computerized tomography scan of the thorax showed a large encapsulated PE in the left lung field, multiple thin walled cysts (≤ 5 mm in diameter) in the lung parenchyma bilaterally, and mediastinal lymphadenopathy - all prominent features of LAM - as well as nodular pulmonary lesions (≤ 3 mm in diameter) consistent with MMPH. Given the persistent nature of the CPE, a five-day course of recombinant human factor XIII (FXIII) was administered intravenously. The chylothorax completely resolved within three months. There has been no recurrence of CPE on follow-up chest X-rays (i.e., total follow-up period of 53 months). This report suggests that the transglutaminase FXIII, a blood coagulation factor, may have an important clinical benefit in treating recurrent or thoracentesis-refractory CPE in TSC-LAM. To our knowledge, this is the first known case in the literature describing the successful treatment of CPE with FXIII in TSC-LAM. Because CPE is rare and there is currently no gold standard for its management, regardless of etiology, further research is warranted to investigate the potential clinical use of FXIII as an effective and safe treatment strategy in selected patients.

RESUMEN

Acute respiratory distress syndrome (ARDS) is an uncommon, highly fatal, and poorly understood manifestation of blastomycosis. Optimal management remains unknown, including the roles of adjunctive corticosteroids and extracorporeal membrane oxygenation (ECMO).We conducted a retrospective chart review of patients with ARDS caused by blastomycosis, managed in intensive care units in Manitoba, Canada, from 1992 to 2014. ARDS was defined using the Berlin definition. Corticosteroid therapy was defined as ≥150 mg cortisol equivalent in 24 hours. Logistic regression was used to identify determinants of a fatal outcome, and bootstrap resampling was used to assess sample size requirements.Forty-three patients with ARDS caused by blastomycosis were identified. ARDS was mild, moderate, and severe in 2 (5%), 12 (28%), and 29 (67%) patients, respectively. Management included amphotericin B (n = 42, 98%), vasopressors (n = 36, 84%), corticosteroids (n = 22, 51%), renal replacement (n = 13, 30%), and ECMO (n = 4, 11%). Seventeen patients (40%) died. All patients treated with ECMO survived (P = 0.14). Corticosteroids were not associated with survival benefit in univariate (P = 0.43) or multivariate analyses (odds ratio 0.52, 95% confidence interval 0.11-2.34). Bootstrap studies indicated that almost 500 patients would be needed to confirm a significant reduction in mortality from corticosteroids (type I error = 0.05, power = 80%).Blastomycosis is an uncommon, albeit important, cause of ARDS in this geographic area. Given the rarity of disease and the large cohort needed to demonstrate mortality benefit, the role of adjunctive therapies, including corticosteroids and ECMO, may remain unconfirmed, and clinical judgment should guide management decisions.

Asunto(s)

Antifúngicos/uso terapéutico , Blastomicosis/complicaciones , Oxigenación por Membrana Extracorpórea/métodos , Glucocorticoides/uso terapéutico , Síndrome de Dificultad Respiratoria , Adulto , Canadá/epidemiología , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Radiografía Torácica/métodos , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/terapia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia

RESUMEN

Background. We performed prospective validation of the cancer ratio (serum LDH : pleural ADA ratio), previously reported as predictive of malignant effusion retrospectively, and assessed the effect of combining it with "pleural lymphocyte count" in diagnosing malignant pleural effusion (MPE). Methods. Prospective cohort study of patients hospitalized with lymphocyte predominant exudative pleural effusion in 2015. Results. 118 patients, 84 (71.2%) having MPE and 34 (28.8%) having tuberculous pleural effusion (TPE), were analysed. In multivariate logistic regression analysis, cancer ratio, serum LDH : pleural fluid lymphocyte count ratio, and "cancer ratio plus" (ratio of cancer ratio and pleural fluid lymphocyte count) correlated positively with MPE. The sensitivity and specificity of cancer ratio, ratio of serum LDH : pleural fluid lymphocyte count, and "cancer ratio plus" were 0.95 (95% CI 0.87-0.98) and 0.85 (95% CI 0.68-0.94), 0.63 (95% CI 0.51-0.73) and 0.85 (95% CI 0.68-0.94), and 97.6 (95% CI 0.90-0.99) and 94.1 (95% CI 0.78-0.98) at the cut-off level of >20, >800, and >30, respectively. Conclusion. Without incurring any additional cost, or requiring additional test, effort, or time, cancer ratio maintained and "cancer ratio plus" improved the specificity of cancer ratio in identifying MPE in the prospective cohort.

Asunto(s)

Adenosina Desaminasa/metabolismo , Exudados y Transudados/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Neoplasias Pulmonares/complicaciones , Derrame Pleural Maligno/diagnóstico , Derrame Pleural/diagnóstico , Tuberculosis Pulmonar/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Diagnóstico Diferencial , Exudados y Transudados/citología , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Derrame Pleural/etiología , Derrame Pleural/metabolismo , Derrame Pleural Maligno/etiología , Derrame Pleural Maligno/metabolismo , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto Joven

RESUMEN

AIM: We studied the diagnostic potential of serum lactate dehydrogenase (LDH) in malignant pleural effusion. METHODS: Retrospective analysis of patients hospitalized with exudative pleural effusion in 2013. RESULTS: Serum LDH and serum LDH: pleural fluid ADA ratio was significantly higher in cancer patients presenting with exudative pleural effusion. In multivariate logistic regression analysis, pleural fluid ADA was negatively correlated 0.62 (0.45-0.85, p = 0.003) with malignancy, whereas serum LDH 1.02 (1.0-1.03, p = 0.004) and serum LDH: pleural fluid ADA ratio 0.94 (0.99-1.0, p = 0.04) was correlated positively with malignant pleural effusion. For serum LDH: pleural fluid ADA ratio, a cut-off level of >20 showed sensitivity, specificity of 0.98 (95 % CI 0.92-0.99) and 0.94 (95 % CI 0.83-0.98), respectively. The positive likelihood ratio was 32.6 (95 % CI 10.7-99.6), while the negative likelihood ratio at this cut-off was 0.03 (95 % CI 0.01-0.15). CONCLUSION: Higher serum LDH and serum LDH: pleural fluid ADA ratio in patients presenting with exudative pleural effusion can distinguish between malignant and non-malignant effusion on the first day of hospitalization. The cut-off level for serum LDH: pleural fluid ADA ratio of >20 is highly predictive of malignancy in patients with exudative pleural effusion (whether lymphocytic or neutrophilic) with high sensitivity and specificity.

Asunto(s)

Adenosina Desaminasa/metabolismo , Hidroliasas/sangre , Neoplasias Pulmonares/complicaciones , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/metabolismo , Proteína C-Reactiva/metabolismo , Exudados y Transudados/metabolismo , Humanos , Hidroliasas/metabolismo , Neoplasias Pulmonares/metabolismo , Derrame Pleural Maligno/etiología , Neumonía/complicaciones , Neumonía/metabolismo , Estudios Retrospectivos , Sensibilidad y Especificidad , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/metabolismo

RESUMEN

In this article, an internationally renowned pulmonologist with extensive experience in teaching and publishing gives practical advice to young physicians and/or residents on the importance of doing research, the steps for planning a project and also some do's and don'ts of writing and publishing a scientific paper.

RESUMEN

BACKGROUND: Septic shock due to Mycobacterium tuberculosis (MTB) is an uncommon but well-recognized clinical syndrome. The objective of this study was to describe the unique clinical characteristics, epidemiologic risk factors, and covariates of survival of patients with MTB septic shock in comparison with other bacterial septic shock. METHODS: A retrospective nested cohort study was conducted of patients given a diagnosis of MTB septic shock derived from a trinational, 8,670-patient database of patients with septic shock between 1996 and 2007. RESULTS: In the database, 53 patients had been given a diagnosis of MTB shock compared with 5,419 with septic shock associated with isolation of more common bacterial pathogens. Patients with MTB and other bacterial septic shock had in-hospital mortality rates of 79.2% and 49.7%, respectively (P < .0001). Of the cases of MTB shock, all but five patients had recognized respiratory tract involvement. Fifty-five percent of patients (29 of 53) were documented (by direct culture or stain) as having disseminated extrapulmonary involvement. Inappropriate and appropriate initial empirical therapy was delivered in 28 patients (52.8%) and 25 patients (47.2%); survival was 7.1% and 36.0%, respectively (P = .0114). Ten patients (18.9%) did not receive anti-MTB therapy; all died. The median time to appropriate antimicrobial therapy for MTB septic shock was 31.0 h (interquartile range, 18.9-71.9 h). Only 11 patients received anti-MTB therapy within 24 h of documentation of hypotension; six of these (54.5%) survived. Only one of 21 patients (4.8%) who started anti-MTB therapy after 24 h survived (P = .0003 vs < 24 h). Survival differences between these time intervals are not significantly different from those seen with bacterial septic shock due to more common bacterial pathogens. CONCLUSIONS: MTB septic shock behaves similarly to bacterial septic shock. As with bacterial septic shock, early appropriate antimicrobial therapy appears to improve mortality.

Asunto(s)

Mycobacterium tuberculosis/aislamiento & purificación , Choque Séptico/microbiología , APACHE , Antibacterianos/uso terapéutico , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Manitoba/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Arabia Saudita/epidemiología , Choque Séptico/tratamiento farmacológico , Choque Séptico/epidemiología , Resultado del Tratamiento , Estados Unidos/epidemiología

RESUMEN

SETTING: Most patients with tuberculous pleural effusions (TPE) have more than 50% lymphocytes in the pleural fluid. Data on patients in whom polymorphonuclear leukocytes (PMNLs) are the predominant cell type are scarce. OBJECTIVE: To compare the clinical, biochemical, microbiological and radiological characteristics between patients with predominantly PMNL and those with lymphocytic TPE. DESIGN: Retrospective analysis of 214 consecutive patients with TPE. RESULTS: The pleural fluid was PMNL-rich in 24 (11%) cases at the time of first thoracocentesis. Compared with those whose pleural fluid was predominantly lymphocytic, these patients showed a higher yield of mycobacteria in culture of sputum (50% vs. 25%, P = 0.03) and pleural fluid (50% vs. 10%, P < 0.01) on solid media, as well as higher pleural adenosine deaminase (ADA) levels (80 vs. 62 U/l, P = 0.02) at the expense of both ADA1 and ADA2 isoenzymes. A shift towards pleural lymphocytic predominance was observed in more than half of the PMNL-predominant patients subjected to repeat thoracocentesis. CONCLUSIONS: The finding of a predominantly PMNL exudate should not rule out TPE, particularly when pleural ADA activity is elevated. The collection of sputum and pleural fluid samples for mycobacterial culture should be encouraged in the case of suspected PMNL-rich TPE, as they are frequently positive in this early stage.

Asunto(s)

Linfocitos , Neutrófilos , Derrame Pleural/inmunología , Tuberculosis Pleural/inmunología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven

RESUMEN

Spatial modulation microscopy (SMM) is a technique originally developed for quantitative spectroscopy of individual nano-objects. Here, a parallel implementation of the SMM technique is demonstrated based on a line detector capable of demodulation at kHz frequencies. The capabilities of the imaging system are shown using an array of plasmonic nanoantennas and dendritic cells incubated with gold nanoparticles.

Asunto(s)

Células Dendríticas/citología , Microscopía/métodos , Imagen Molecular/métodos , Nanopartículas , Factores de Tiempo

Asunto(s)

Benzodiazepinas/efectos adversos , Dantroleno/efectos adversos , Eosinofilia/inducido químicamente , Enfermedad Iatrogénica , Relajantes Musculares Centrales/efectos adversos , Derrame Pericárdico/inducido químicamente , Derrame Pleural/inducido químicamente , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Humanos , Masculino

RESUMEN

Oil bodies were observed in cells of both embryo and aleurone layers of mature adlay grains (Coix lachryma-jobi L. var. ma-yuen Stapf). Stable oil bodies were successfully isolated from the adlay grains. Thin-layer chromatography revealed that the contents stored in the adlay oil bodies were mainly neutral lipids (>90% triacylglycerols and about 5% diacylglycerols). The integrity of the isolated oil bodies was presumably maintained via electronegative repulsion and steric hindrance provided by their surface proteins. Immunological cross-recognition using antibodies against sesame oil-body proteins indicated that two oleosin isoforms (termed oleosin-H and oleosin-L) and one caleosin were present in the adlay oil bodies. Full-length cDNA fragments encoding these three unique oil-body proteins were obtained by PCR cloning. MALDI-MS analyses confirmed that the three full-length cDNA fragments encoded the two oleosin isoforms and one caleosin observed in the oil bodies isolated from the adlay grains.

Asunto(s)

Coix/ultraestructura , Cuerpos de Inclusión/química , Aceites de Plantas/análisis , Proteínas de Unión al Calcio , Cromatografía en Capa Delgada , Coix/química , ADN Complementario , Lípidos/análisis , Datos de Secuencia Molecular , Proteínas de Plantas , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción

Asunto(s)

Derrame Pleural/diagnóstico por imagen , Pleuroneumonía/diagnóstico por imagen , Humanos , Derrame Pleural/complicaciones , Pleuroneumonía/complicaciones , Tomografía Computarizada por Rayos X

RESUMEN

About 20% of hospitalized patients with bacterial pneumonia have an accompanying pleural effusion. Parapneumonic effusions (PPE) are associated with a considerable morbidity and mortality. The main decision in managing a patient with a PPE is whether to insert a chest tube (complicated PPE). Imaging (i.e., chest radiograph, ultrasound and computed tomography) and pleural fluid analysis (i.e., pH, glucose, lactate dehydrogenase, bacterial cults) provide essential information for patient management. Therefore, all PPEs should be aspirated for diagnostic purposes. This may require image-guidance if the effusion is small or heavily loculated. According to the current guidelines, any PPE that fulfills at least one of the following criteria should be drained: size > or = 1/2 of the hemithorax, loculations, pleural fluid pH < 7.20 (or alternatively pleural fluid glucose < 60 mg/dl), positive pleural fluid Gram stain or culture, or purulent appearance. The key components of the treatment of complicated PPE and empyema are the use of appropriate antibiotics, provision of nutritional support, and drainage of the pleural space by one of the following methods: therapeutic thoracentesis, tube thoracostomy, intrapleural fibrinolytics, thoracoscopy with breakdown of adhesions or thoracotomy with decortication. The routine use of intrapleural fibrinolytic therapy remains controversial. (c) 2009 Elsevier España, S.L. All rights reserved.

Asunto(s)

Empiema Pleural/diagnóstico , Empiema Pleural/terapia , Derrame Pleural/diagnóstico , Derrame Pleural/terapia , Adulto , Árboles de Decisión , Humanos

RESUMEN

In septic shock, cardiovascular collapse is caused by the release of inflammatory mediators. We previously found that lysozyme (Lzm-S), released from leukocytes, contributed to the myocardial depression and arterial vasodilation that develop in canine models of septic shock. To cause vasodilation, Lzm-S generates hydrogen peroxide (H(2)O(2)) that activates the smooth muscle soluble guanylate cyclase (sGC) pathway, although the mechanism of H(2)O(2) generation is not known. To cause myocardial depression, Lzm-S binds to the endocardial endothelium, resulting in the formation of nitric oxide (NO) and subsequent activation of myocardial sGC, although the initial signaling event is not clear. In this study, we examined whether the myocardial depression produced by Lzm-S was also caused by the generation of H(2)O(2) and whether Lzm-S could intrinsically generate H(2)O(2) as has been described for other protein types. In a canine ventricular trabecular preparation, we found that the peroxidizing agent Aspergillus niger catalase, that would breakdown H(2)O(2), prevented Lzm-S- induced decrease in contraction. We also found that compound I, a species of catalase formed during H(2)O(2) metabolism, could contribute to the NO generation caused by Lzm-S. In tissue-free experiments, we used a fluorometric assay (Ultra Amplex red H(2)O(2) assay) and electrochemical sensor techniques, respectively, to measure H(2)O(2) generation. We found that Lzm-S could generate H(2)O(2) and, furthermore, that this generation could be attenuated by the singlet oxygen quencher sodium azide. This study shows that Lzm-S, a mediator of sepsis, is able to intrinsically generate H(2)O(2). Moreover, this generation may activate H(2)O(2)-dependent pathways leading to cardiovascular collapse in septic shock.

Asunto(s)

Enfermedades Cardiovasculares/metabolismo , Peróxido de Hidrógeno/metabolismo , Muramidasa/metabolismo , Contracción Miocárdica/fisiología , Choque Séptico/metabolismo , Animales , Aspergillus niger/enzimología , Enfermedades Cardiovasculares/inmunología , Catalasa/farmacología , Perros , Inhibidores Enzimáticos/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III/metabolismo , Consumo de Oxígeno/fisiología , Especies Reactivas de Oxígeno/metabolismo , Choque Séptico/inmunología , omega-N-Metilarginina/farmacología

RESUMEN

Although eosinophilic pleural effusion (EPE) has been a subject of numerous studies, its clinical significance still remains unclear. The aim of our study was to evaluate: 1) the relative incidence and aetiology of EPE; 2) the predictors of malignancy in patients with EPE; and 3) the relationship between repeated thoracentesis and pleural fluid eosinophilia. A retrospective analysis of 2,205 pleural fluid samples from 1,868 patients treated between 1995 and 2007 was performed. We identified 135 patients with EPE (7.2% of all patients with pleural effusion) and 153 EPE samples. The most common condition associated with EPE was malignancy (34.8%) followed by infectious (19.2%), unknown (14.1%), post-traumatic (8.9%) and miscellaneous (23.0%) pleural effusions. The incidence of malignancy was significantly higher in patients with a lower (< or =40%) pleural fluid eosinophil percentage. 40 patients with EPE underwent a second thoracentesis. In 16, eosinophilia was present in both pleural fluid samples, 14 revealed pleural fluid eosinophilia only after the second thoracentesis and 10 had eosinophilia only in the first pleural fluid sample. Pleural fluid eosinophilia should not be regarded as a predictor of nonmalignant aetiology. Probability of malignancy is lower in effusions with a high eosinophil percentage. The incidence of EPE in patients undergoing second thoracentesis is not different to that found during the first thoracentesis.

Asunto(s)

Eosinófilos/citología , Eosinófilos/patología , Derrame Pleural/epidemiología , Derrame Pleural/etiología , Adulto , Anciano , Anciano de 80 o más Años , Automatización , Eosinofilia , Eritrocitos/patología , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Neumología , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

The ability to diagnose and treat infectious diseases and handle infectious disease outbreaks continues to improve. For the most part, the major plagues of antiquity remain historical footnotes, yet, despite many advances, there is clear evidence that major pandemic illness is always just one outbreak away. In addition to the HIV pandemic, the smaller epidemic outbreaks of Legionnaire's disease, hantavirus pulmonary syndrome, and severe acute respiratory syndrome, among many others, points out the potential risk associated with a lack of preplanning and preparedness. Although pandemic influenza is at the top of the list when discussing possible future major infectious disease outbreaks, the truth is that the identity of the next major pandemic pathogen cannot be predicted with any accuracy. We can only hope that general preparedness and the lessons learned from previous outbreaks suffice.

Asunto(s)

Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/historia , Cuidados Críticos/historia , Brotes de Enfermedades/historia , Enfermedades Endémicas/historia , Unidades de Cuidados Intensivos/historia , Adolescente , Adulto , Niño , Infecciones Comunitarias Adquiridas/terapia , Brotes de Enfermedades/prevención & control , Enfermedades Endémicas/prevención & control , Fascitis Necrotizante/historia , Fascitis Necrotizante/terapia , Femenino , Salud Global , Síndrome Pulmonar por Hantavirus/historia , Síndrome Pulmonar por Hantavirus/terapia , Historia del Siglo XX , Humanos , Gripe Humana/historia , Gripe Humana/terapia , Enfermedad de los Legionarios/historia , Enfermedad de los Legionarios/terapia , Masculino , Pneumocystis carinii , Neumonía por Pneumocystis/historia , Neumonía por Pneumocystis/terapia , Poliomielitis/historia , Poliomielitis/terapia , Síndrome Respiratorio Agudo Grave/historia , Síndrome Respiratorio Agudo Grave/terapia , Choque Séptico/historia , Choque Séptico/terapia , Infecciones Estafilocócicas/historia , Infecciones Estafilocócicas/terapia , Infecciones Estreptocócicas/historia , Infecciones Estreptocócicas/terapia , Adulto Joven

RESUMEN

Blastomycosis is a granulomatous infection caused by the thermally dimorphic fungus, Blastomyces dermatitidis, for which seasonal variation has been proposed. We conducted a retrospective review of medical records of 324 patients with blastomycosis in Manitoba and northwestern Ontario. The average age of patients at the time of diagnosis was 39+/-20 (range, 0-85) years. Symptoms referable to blastomycosis were first noted in the autumn and winter (September to February) by 63% of the patients. The seasonal distribution of cases was different for localized pulmonary infection than the disseminated disease (P<0.0001). For localized lung disease, the peak incidence of symptom onset occurred in the autumn, and lowest incidence in the spring; one half (50%) of the patients with diffuse lung disease had onset of symptoms in the spring months and a few (11%) cases occurred during the summer. We noted a distinct seasonal variation in the clinical presentation of blastomycosis. The observed pattern suggests that summer environmental exposure and acquisition of the infection results in an early (1-6 months) localized pneumonia in the majority of cases, followed by later (4-9 months) reactivation or slow progression of asymptomatic infection resulting in isolated extrapulmonary or disseminated hematogenous disease in the minority.

Asunto(s)

Blastomyces/aislamiento & purificación , Blastomicosis/epidemiología , Enfermedades Pulmonares Fúngicas/epidemiología , Estaciones del Año , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Blastomicosis/diagnóstico por imagen , Blastomicosis/microbiología , Distribución de Chi-Cuadrado , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Pulmón/diagnóstico por imagen , Pulmón/microbiología , Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Enfermedades Pulmonares Fúngicas/microbiología , Masculino , Manitoba/epidemiología , Persona de Mediana Edad , Ontario/epidemiología , Radiografía , Estudios Retrospectivos , Distribución por Sexo

RESUMEN

In septic shock, systemic vasodilation and myocardial depression contribute to the systemic hypotension observed. Both components can be attributed to the effects of mediators that are released as part of the inflammatory response. We previously found that lysozyme (Lzm-S), released from leukocytes, contributed to the myocardial depression that develops in a canine model of septic shock. Lzm-S binds to the endocardial endothelium, resulting in the production of nitric oxide (NO), which, in turn, activates the myocardial soluble guanylate cyclase (sGC) pathway. In the present study, we determined whether Lzm-S might also play a role in the systemic vasodilation that occurs in septic shock. In a phenylephrine-contracted canine carotid artery ring preparation, we found that both canine and human Lzm-S, at concentrations similar to those found in sepsis, produced vasorelaxation. This decrease in force could not be prevented by inhibitors of NO synthase, prostaglandin synthesis, or potassium channel inhibitors and was not dependent on the presence of the vascular endothelium. However, inhibitors of the sGC pathway prevented the vasodilatory activity of Lzm-S. In addition, Aspergillus niger catalase, which breaks down H(2)O(2), as well as hydroxyl radical scavengers, which included hydroquinone and mannitol, prevented the effect of Lzm-S. Electrochemical sensors corroborated that Lzm-S caused H(2)O(2) release from the carotid artery preparation. In conclusion, these results support the notion that when Lzm-S interacts with the arterial vasculature, this interaction results in the formation of H(2)O(2), which, in turn, activates the sGC pathway to cause relaxation. Lzm-S may contribute to the vasodilation that occurs in septic shock.

Asunto(s)

Arteria Carótida Interna/metabolismo , Peróxido de Hidrógeno/metabolismo , Arteria Mesentérica Superior/metabolismo , Muramidasa/metabolismo , Óxido Nítrico/metabolismo , Sepsis/metabolismo , Transducción de Señal , Vasodilatación , Aminoquinolinas/farmacología , Animales , Arteria Carótida Interna/efectos de los fármacos , Arteria Carótida Interna/enzimología , Catalasa/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , GMP Cíclico/farmacología , Proteínas Quinasas Dependientes de GMP Cíclico/antagonistas & inhibidores , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Inhibidores de la Ciclooxigenasa/farmacología , Perros , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Etanol/farmacología , Depuradores de Radicales Libres/farmacología , Guanilato Ciclasa/antagonistas & inhibidores , Guanilato Ciclasa/metabolismo , Humanos , Hidroquinonas/farmacología , Técnicas In Vitro , Indometacina/farmacología , Manitol/farmacología , Arteria Mesentérica Superior/efectos de los fármacos , Arteria Mesentérica Superior/enzimología , Azul de Metileno/farmacología , Muramidasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Oxadiazoles/farmacología , Fenilefrina/farmacología , Prostaglandinas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Quinoxalinas/farmacología , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Receptores Citoplasmáticos y Nucleares/metabolismo , Sepsis/fisiopatología , Transducción de Señal/efectos de los fármacos , Guanilil Ciclasa Soluble , Tionucleótidos/farmacología , Factores de Tiempo , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos , omega-N-Metilarginina/farmacología

RESUMEN

Cardiovascular dysfunction in septic shock (SS) is ascribed to the release of inflammatory mediators. Norepinephrine (NE) is often administered to treat low MAP in SS. We recently found that lysozyme c (Lzm-S) released from leukocytes was a mediator of myocardial depression in an Escherichia coil model of SS in dogs. This effect can be blocked in an in vitro preparation by chitobiose, a competitive inhibitor of Lzm-S. In the present study, we examined whether chitobiose treatment can reverse myocardial depression and obviate NE requirements in two respective canine E. coli preparations. In a 6-h study, we administered chitobiose after 3.5 h of E. coli bacteremia and compared stroke work (SW) and MAP at 6 h with a sepsis control group. In a 12-h study, we determined whether chitobiose treatment can reduce the need for NE requirements during 12 h of bacteremia. In the latter study, either chitobiose or NE was given when MAP decreased approximately 20% from the presepsis value in respective groups. In anesthetized, mechanically ventilated dogs, we monitored hemodynamic parameters during continuous E. coli infusion. In the 6-h study, chitobiose improved SW and MAP at the 6-h period as compared with the nontreated sepsis group. In the 12-h study, SW and MAP increased after chitobiose without the necessity of NE administration. These results suggest that inhibitors of Lzm-S such as chitobiose may improve myocardial depression and reduce the need for NE requirements in SS.

Asunto(s)

Cardiomiopatías/tratamiento farmacológico , Disacáridos/farmacología , Inhibidores Enzimáticos/farmacología , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli , Muramidasa/antagonistas & inhibidores , Norepinefrina/farmacología , Choque Séptico/tratamiento farmacológico , Vasoconstrictores/farmacología , Animales , Bacteriemia/tratamiento farmacológico , Bacteriemia/enzimología , Bacteriemia/fisiopatología , Cardiomiopatías/enzimología , Cardiomiopatías/fisiopatología , Perros , Infecciones por Escherichia coli/enzimología , Infecciones por Escherichia coli/fisiopatología , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Choque Séptico/enzimología , Choque Séptico/fisiopatología , Volumen Sistólico/efectos de los fármacos , Factores de Tiempo

RESUMEN

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are important causes of morbidity and mortality, with mortality rates approaching 62%. HAP and VAP are the second most common cause of nosocomial infection overall, but are the most common cause documented in the intensive care unit setting. In addition, HAP and VAP produce the highest mortality associated with nosocomial infection. As a result, evidence-based guidelines were prepared detailing the epidemiology, microbial etiology, risk factors and clinical manifestations of HAP and VAP. Furthermore, an approach based on the available data, expert opinion and current practice for the provision of care within the Canadian health care system was used to determine risk stratification schemas to enable appropriate diagnosis, antimicrobial management and nonantimicrobial management of HAP and VAP. Finally, prevention and risk-reduction strategies to reduce the risk of acquiring these infections were collated. Future initiatives to enhance more rapid diagnosis and to effect better treatment for resistant pathogens are necessary to reduce morbidity and improve survival.