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2.
Eur J Med Res ; 28(1): 568, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38053110

RESUMO

BACKGROUND: In 2022/2023, Influenza A and Respiratory Syncytial Virus (RSV) reappeared in hospitalized patients, which was in parallel to ongoing SARS-CoV-2 infections. The aim of our study was to compare the characteristics and outcomes of these infections during the same time. METHODS: We included patients of all ages with a positive polymerase chain reaction (PCR) test for Influenza A/B, RSV, or SARS-CoV-2 virus hospitalized in the neurological, internal or paediatric units of the RoMed Hospital Rosenheim, Germany, between October 1st 2022 and February 28th 2023. RESULTS: A total of 906 patients were included (45.6% female; median age 68.0 years; 21.9% Influenza A, 48.2% SARS-CoV-2, 28.3% RSV). Influenza B (0.2%) and co-infections (1.5%) played a minor role. In patients aged ≥ 18 years (n = 637, 71%), Influenza A, SARS-CoV-2 and RSV groups differed in age (median 72, 79, 76 years, respectively; p < 0.001). Comorbidities, particularly asthma and COPD, were most prevalent for RSV. 103 patients were admitted to the intensive care unit (ICU) (16.3% Influenza A, 15.3% SARS-CoV-2, 19.2% RSV; p = 0.649), 56 died (6.8% Influenza A, 9% SARS-CoV-2, 11.1% RSV; p = 0.496). RSV showed the highest frequencies of low-flow oxygen supplementation for admission and stay. Differences in the length of stay were minor (median 7 days). Conversely, in patients aged < 18 years (n = 261, 28,8%), 19.5%, 17.6% and 60.2% were in the Influenza A, SARS-CoV-2 and RSV groups, respectively; 0.4% showed Influenza B and 2.3% co-infections. 17 patients were admitted to ICU (3.9% Influenza A, 9.6% RSV, 0% SARS-CoV-2); none died. RSV showed the highest frequencies of high- and low-flow oxygen supplementation, SARS-CoV-2 the lowest. CONCLUSION: When comparing infections with Influenza, SARS-CoV-2 and RSV in the winter 2022/2023 in hospitalized adult patients, rates of ICU admission and mortality were similar. RSV showed the highest frequencies of obstructive airway diseases, and of oxygen supplementation. The latter was also true in children/adolescents, in whom RSV dominated. Thus, in the situation of declining importance of SARS-CoV-2, RSV showed a disease burden that was relatively higher than that from Influenza and SARS-CoV-2 across ages, and this might be relevant for the seasons coming.


Assuntos
COVID-19 , Coinfecção , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Adulto , Criança , Adolescente , Humanos , Feminino , Idoso , Masculino , Vírus Sinciciais Respiratórios , Influenza Humana/epidemiologia , SARS-CoV-2 , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/terapia , Estações do Ano , COVID-19/epidemiologia , Atenção Primária à Saúde
3.
Pathologie (Heidelb) ; 43(5): 377-380, 2022 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-35376988

RESUMO

A case of a patient suffering from COVID-19 with suspected associated myositis is reported, in which the initially limited information about the history and disease course led to difficulties in establishing a reasonable diagnosis. Through inquiry, further data could be collected, so that the diagnosis of an infection-associated thrombotic microangiopathy in the context of a Morganella morganii myositis could be made. This patient study shows that even in times of the omnipresent pandemic and despite the context of a positive COVID-19 test result, differential diagnoses and the integrative clinicopathologic approach in interpreting muscle biopsy findings should not be neglected.


Assuntos
COVID-19 , Miosite , Biópsia , Progressão da Doença , Humanos , Músculos/patologia , Miosite/diagnóstico , Pandemias
4.
Int J Comput Assist Radiol Surg ; 11(6): 1051-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27072836

RESUMO

PURPOSE: Patient-specific biomechanical simulations of the behavior of soft tissue gain importance in current surgery assistance systems as they can provide surgeons with valuable ancillary information for diagnosis and therapy. In this work, we aim at supporting minimally invasive mitral valve reconstruction (MVR) surgery by providing scenario setups for FEM-based soft tissue simulations, which simulate the behavior of the patient-individual mitral valve subject to natural forces during the cardiac cycle after an MVR. However, due to the complexity of these simulations and of their underlying mathematical models, it is difficult for non-engineers to sufficiently understand and adequately interpret all relevant modeling and simulation aspects. In particular, it is challenging to set up such simulations in automated preprocessing workflows such that they are both patient-specific and still maximally comprehensive with respect to the model. METHODS: In this paper, we address this issue and present a fully automated chain of preprocessing operators for setting up comprehensive, patient-specific biomechanical models on the basis of patient-individual medical data. These models are suitable for FEM-based MVR surgery simulation. The preprocessing methods are integrated into the framework of the Medical Simulation Markup Language and allow for automated information processing in a data-driven pipeline. RESULTS: We constructed a workflow for holistic, patient-individual information preprocessing for MVR surgery simulations. In particular, we show how simulation preprocessing can be both fully automated and still patient-specific, when using a series of dedicated MVR data analytics operators. The outcome of our operator chain is visualized in order to help the surgeon understand the model setup. CONCLUSION: With this work, we expect to improve the usability of simulation-based MVR surgery assistance, through allowing for fully automated, patient-specific simulation setups. Combined visualization of the biomechanical model setup and of the corresponding surgery simulation results fosters the understandability and transparency of our assistance environment.


Assuntos
Anuloplastia da Valva Mitral/métodos , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Modelos Anatômicos , Modelagem Computacional Específica para o Paciente , Fenômenos Biomecânicos , Procedimentos Cirúrgicos Cardíacos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
5.
Artigo em Alemão | MEDLINE | ID: mdl-26235357

RESUMO

Ostrich farming and keeping in Germany is of increasing interest. Ostrich farming includes keeping the animals as agricultural livestock (production of meat, leather, eggs), for display, hobby farming and keeping in zoological collections. Based on scientific research there is a steady increase in knowledge of keeping ratites according to sophisticated standards in terms of animal welfare legislation. Legislation and recommondations for keeping of ratitae are described.


Assuntos
Criação de Animais Domésticos/educação , Criação de Animais Domésticos/legislação & jurisprudência , Bem-Estar do Animal/legislação & jurisprudência , Paleógnatas , Animais , Alemanha
6.
Int J Comput Assist Radiol Surg ; 10(6): 749-59, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25847671

RESUMO

PURPOSE: Malignant neoplasms of the liver are among the most frequent cancers worldwide. Given the diversity of options for liver cancer therapy, the choice of treatment depends on various parameters including patient condition, tumor size and location, liver function, and previous interventions. To address this issue, we present the first approach to treatment strategy planning based on holistic processing of patient-individual data, practical knowledge (i.e., case knowledge), and factual knowledge (e.g., clinical guidelines and studies). METHODS: The contributions of this paper are as follows: (1) a formalized dynamic patient model that incorporates all the heterogeneous data acquired for a specific patient in the whole course of disease treatment; (2) a concept for formalizing factual knowledge; and (3) a technical infrastructure that enables storing, accessing, and processing of heterogeneous data to support clinical decision making. RESULTS: Our patient model, which currently covers 602 patient-individual parameters, was successfully instantiated for 184 patients. It was sufficiently comprehensive to serve as the basis for the formalization of a total of 72 rules extracted from studies on patients with colorectal liver metastases or hepatocellular carcinoma. For a subset of 70 patients with these diagnoses, the system derived an average of [Formula: see text] assertions per patient. CONCLUSION: The proposed concept paves the way for holistic treatment strategy planning by enabling joint storing and processing of heterogeneous data from various information sources.


Assuntos
Carcinoma Hepatocelular/cirurgia , Tomada de Decisão Clínica , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Modelos Anatômicos , Carcinoma Hepatocelular/secundário , Neoplasias Colorretais/secundário , Humanos , Neoplasias Hepáticas/patologia
7.
Br J Pharmacol ; 171(5): 1210-30, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24641185

RESUMO

The blood-brain barrier (BBB) is a complex vascular structure consisting of microvascular endothelial cells that line the vessel wall, astrocyte end-feet, pericytes, as well as the basal lamina. BBB cells act in concert to maintain the characteristic impermeable and low paracellular flux of the brain vascular network, thus ensuring a homeostatic neuronal environment. Alterations in BBB stability that occur during injury have dire consequences on disease progression and it is clear that BBB cell-specific responses, positive or negative, must make a significant contribution to injury outcome. Reduced oxygenation, or hypoxia, is a characteristic of many brain diseases that significantly increases barrier permeability. Recent data suggest that hypoxia-inducible factor (HIF-1), the master regulator of the hypoxic response, probably mediates many hypoxic effects either directly or indirectly via its target genes. This review discusses current knowledge of physiological cell-specific regulation of barrier function, their responses to hypoxia as well as consequences of hypoxic- and HIF-1-mediated mechanisms on barrier integrity during select brain diseases. In the final sections, the potential of current advances in targeting HIF-1 as a therapeutic strategy will be overviewed.


Assuntos
Barreira Hematoencefálica/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/metabolismo , Animais , Astrócitos/metabolismo , Barreira Hematoencefálica/citologia , Células Endoteliais/metabolismo , Humanos , Pericitos/metabolismo
9.
Stereotact Funct Neurosurg ; 91(3): 162-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23446024

RESUMO

BACKGROUND: Neurosurgeons regularly plan their surgery using magnetic resonance imaging (MRI) images, which may show a clear distinction between the area to be resected and the surrounding healthy brain tissue depending on the nature of the pathology. However, this distinction is often unclear with the naked eye during the surgical intervention, and it may be difficult to infer depth and an accurate volumetric interpretation from a series of MRI image slices. OBJECTIVES: In this work, MRI data are used to create affordable patient-specific 3-dimensional (3D) scale models of the brain which clearly indicate the location and extent of a tumour relative to brain surface features and important adjacent structures. METHODS: This is achieved using custom software and rapid prototyping. In addition, functionally eloquent areas identified using functional MRI are integrated into the 3D models. RESULTS: Preliminary in vivo results are presented for 2 patients. The accuracy of the technique was estimated both theoretically and by printing a geometrical phantom, with mean dimensional errors of less than 0.5 mm observed. CONCLUSIONS: This may provide a practical and cost-effective tool which can be used for training, and during neurosurgical planning and intervention.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/patologia , Imageamento Tridimensional/métodos , Procedimentos Neurocirúrgicos/métodos , Adulto , Encéfalo/cirurgia , Humanos , Imageamento por Ressonância Magnética , Modelos Anatômicos , Período Pré-Operatório
10.
J Toxicol Environ Health A ; 74(10): 678-91, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21432717

RESUMO

As part of a longitudinal surveillance program, 35 members of a larger dynamic cohort of 79 Gulf War I veterans exposed to depleted uranium (DU) during combat underwent clinical evaluation at the Baltimore Veterans Administration Medical Center. Health outcomes and biomonitoring results were obtained to assess effects of DU exposure and determine the need for additional medical intervention. Clinical evaluation included medical and exposure histories, physical examination, and laboratory studies including biomarkers of uranium (U) exposure. Urine collections were obtained for U analysis and to measure renal function parameters. Other laboratory measures included basic hematology and chemistry parameters, blood and plasma U concentrations, and markers of bone metabolism. Urine U (uU) excretion remained above normal in participants with embedded DU fragments, with urine U concentrations ranging from 0.006 to 1.88 µg U/g creatinine. Biomarkers of renal effects showed no apparent evidence of renal functional changes or cellular toxicity related to U body burden. No marked differences in markers of bone formation or bone resorption were observed; however, a statistically significant decrease in levels of serum intact parathyroid hormone and significant increases in urinary calcium and sodium excretion were seen in the high versus the low uU groups. Eighteen years after first exposure, members of this cohort with DU fragments continue to excrete elevated concentrations of uU. No significant evidence of clinically important changes was observed in kidney or bone, the two principal target organs of U. Continued surveillance is prudent, however, due to the ongoing mobilization of uranium from fragment depots.


Assuntos
Guerra do Golfo , Substâncias Perigosas/toxicidade , Exposição Ocupacional/análise , Urânio/toxicidade , Veteranos/estatística & dados numéricos , Armas , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Creatinina/urina , Monitoramento Ambiental , Monitoramento Epidemiológico , Substâncias Perigosas/sangue , Substâncias Perigosas/urina , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/estatística & dados numéricos , Urânio/sangue , Urânio/urina , Ferimentos por Arma de Fogo/epidemiologia
11.
J Toxicol Environ Health A ; 72(1): 14-29, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18979351

RESUMO

As part of a longitudinal surveillance program, 35 members of a larger cohort of 77 Gulf War I veterans who were victims of depleted uranium (DU) "friendly fire" during combat underwent a 3-day clinical assessment at the Baltimore Veterans Administration Medical Center (VAMC). The assessment included a detailed medical history, exposure history, physical examination, and laboratory studies. Spot and 24-h urine collections were obtained for renal function parameters and for urine uranium (U) measures. Blood U measures were also performed. Urine U excretion was significantly associated with DU retained shrapnel burden (8.821 mug U/g creatinine [creat.] vs. 0.005 mug U/g creat., p = .04). Blood as a U sampling matrix revealed satisfactory results for measures of total U with a high correlation with urine U results (r = .84) when urine U concentrations were >/=0.1 mug/g creatinine. However, isotopic results in blood detected DU in only half of the subcohort who had isotopic signatures for DU detectable in urine. After stratifying the cohort based on urine U concentration, the high-U group showed a trend toward higher concentrations of urine beta(2) microglobulin compared to the low-U group (81.7 v. 69.0 mug/g creat.; p = .11 respectively) and retinol binding protein (48.1 vs. 31.0 mug/g creat.; p = .07 respectively). Bone metabolism parameters showed only subtle differences between groups. Sixteen years after first exposure, this cohort continues to excrete elevated concentrations of urine U as a function of DU shrapnel burden. Although subtle trends emerge in renal proximal tubular function and bone formation, the cohort exhibits few clinically significant U-related health effects.


Assuntos
Guerra do Golfo , Exposição Ocupacional/análise , Vigilância da População , Urânio/intoxicação , Veteranos , Adulto , Baltimore , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/urina , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Humanos , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/fisiopatologia , Estudos Longitudinais , Masculino , Reprodução/efeitos dos fármacos , Urânio/análise , Microglobulina beta-2/urina
12.
Health Phys ; 93(1): 60-73, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17563493

RESUMO

A cohort of seventy-four 1991 Gulf War soldiers with known exposure to depleted uranium (DU) resulting from their involvement in friendly-fire incidents with DU munitions is being followed by the Baltimore Veterans Affairs Medical Center. Biennial medical surveillance visits designed to identify uranium-related changes in health have been conducted since 1993. On-going systemic exposure to DU in veterans with embedded metal fragments is indicated by elevated urine uranium (U) excretion at concentrations up to 1,000-fold higher than that seen in the normal population. Health outcome results from the subcohort of this group of veterans attending the 2005 surveillance visit were examined based on two measures of U exposure. As in previous years, current U exposure is measured by determining urine U concentration at the time of their surveillance visit. A cumulative measure of U exposure was also calculated based on each veteran's past urine U concentrations since first exposure in 1991. Using either exposure metric, results continued to show no evidence of clinically significant DU-related health effects. Urine concentrations of retinol binding protein (RBP), a biomarker of renal proximal tubule function, were not significantly different between the low vs. high U groups based on either the current or cumulative exposure metric. Continued evidence of a weak genotoxic effect from the on-going DU exposure as measured at the HPRT (hypoxanthine-guanine phosphoribosyl transferase) locus and suggested by the fluorescent in-situ hybridization (FISH) results in peripheral blood recommends the need for continued surveillance of this population.


Assuntos
Guerra do Golfo , Exposição Ocupacional/efeitos adversos , Urânio/toxicidade , Veteranos , Adulto , Aberrações Cromossômicas/efeitos da radiação , Inquéritos Epidemiológicos , Humanos , Hipoxantina Fosforribosiltransferase/genética , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Militares , Mutação , Vigilância da População , Proteínas de Ligação ao Retinol/urina , Sêmen/citologia , Sêmen/efeitos da radiação , Urânio/urina
13.
J Trauma ; 51(6): 1049-53, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11740249

RESUMO

BACKGROUND: Improved outcomes following lung injury have been reported using "lung sparing" techniques. METHODS: A retrospective multicenter 4-year review of patients who underwent lung resection following injury was performed. Resections were categorized as "minor" (suture, wedge resection, tractotomy) or "major" (lobectomy or pneumonectomy). Injury severity, Abbreviated Injury Scale (AIS) score, and outcome were recorded. RESULTS: One hundred forty-three patients (28 blunt, 115 penetrating) underwent lung resection after sustaining an injury. Minor resections were used in 75% of cases, in patients with less severe thoracic injury (chest AIS scores "minor" 3.8 +/- 0.9 vs. "major" 4.3 +/- 0.7, p = 0.02). Mortality increased with each step of increasing complexity of the surgical technique (RR, 1.8; CI, 1.4-2.2): suture alone, 9% mortality; tractotomy, 13%; wedge resection, 30%; lobectomy, 43%; and pneumonectomy, 50%. Regression analysis demonstrated that blunt mechanism, lower blood pressure at thoracotomy, and increasing amount of the lung resection were each independently associated with mortality. CONCLUSION: Blunt traumatic lung injury has higher mortality primarily due to associated extrathoracic injuries. Major resections are required more commonly than previously reported. While "minor" resections, if feasible, are associated with improved outcome, trauma surgeons should be facile in a wide range of technical procedures for the management of lung injuries.


Assuntos
Lesão Pulmonar , Pulmão/cirurgia , Toracotomia/mortalidade , Ferimentos não Penetrantes/cirurgia , Ferimentos Penetrantes/cirurgia , Adulto , Tratamento de Emergência , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Prontuários Médicos , Estudos Retrospectivos , Toracotomia/métodos , Resultado do Tratamento , Estados Unidos/epidemiologia , Ferimentos não Penetrantes/mortalidade , Ferimentos Penetrantes/mortalidade
14.
Circulation ; 104(21): 2602-7, 2001 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-11714657

RESUMO

BACKGROUND: Angiotensin II activates 2 distinct G protein-coupled receptors, the AT(1) and AT(2) receptors. Most of the known cardiovascular effects of angiotensin II are mediated by the AT(1) receptor subtype. The aim of the present study was to test whether deletion of the AT(2) receptor gene in mice (AT(2)-KO mice) leads to long-term functional or structural alterations in the cardiovascular system. METHODS AND RESULTS: In vivo pressure responses to angiotensin II or the alpha(1)-adrenergic receptor agonist phenylephrine were greatly enhanced in AT(2)-KO mice. Deletion of the angiotensin AT(2) receptor did not lead to a compensatory increase of the activity of the circulating renin-angiotensin system, and arterial blood pressure was identical in wild-type control mice (WT) and AT(2)-KO mice. Cardiac contractility as assessed by LV catheterization and by rapid MRI also did not differ between AT(2)-KO and WT mice. Isolated femoral arteries from AT(2)-KO mice, however, showed enhanced vasoconstriction to angiotensin II, norepinephrine, and K(+) depolarization compared with WT. Morphometric analysis of large and small femoral arteries revealed a significant hypertrophy of media smooth muscle cells. Phospho-P70S6 kinase levels were significantly increased in aortas from AT(2)-KO mice compared with WT mice. Treatment of mice with an ACE inhibitor for 8 weeks abolished the increased pressure responsiveness, vascular hypertrophy, and enhanced P70S6 kinase phosphorylation in AT(2)-KO mice. CONCLUSIONS: These results indicate that vascular AT(2) receptors inhibit the activity and, hence, hypertrophic signaling by the P70S6 kinase in vivo and thus are important regulators of vascular structure and function.


Assuntos
Receptores de Angiotensina/genética , Receptores de Angiotensina/fisiologia , Proteínas Quinases S6 Ribossômicas/metabolismo , Doenças Vasculares/etiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Pressão Sanguínea , Captopril/farmacologia , Técnicas de Cultura , Coração/fisiopatologia , Hemodinâmica , Hipertrofia/etiologia , Hipertrofia/patologia , Hipertrofia/fisiopatologia , Imageamento por Ressonância Magnética , Camundongos , Camundongos Knockout , Miografia , Fosforilação , Receptor Tipo 2 de Angiotensina , Transdução de Sinais , Doenças Vasculares/patologia , Doenças Vasculares/fisiopatologia , Vasoconstrição
16.
J Trauma ; 51(4): 633-7; discussion 637-8, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11586151

RESUMO

BACKGROUND: Safer cars, decreased violence, and nonoperative management have changed the trauma patient's nature. We evaluated changes in a Level I trauma center over 15 years and considered their effect on trauma surgeons. METHODS: From January 1985 through August 1999, 16,799 trauma registry patients were analyzed for mechanism of injury, Injury Severity Score, and procedures. RESULTS: Mean Injury Severity Score decreased from 15.9 to 10.7 and length of stay fell from 8.0 days to 5.9 days. There were significant decreases in penetrating trauma admissions and percentage of patients with Abbreviated Injury Scale score > 3 for head, chest, and abdomen. Frequency of craniotomy, thoracotomy, and laparotomy dropped dramatically. CONCLUSION: Significant decreases in injury severity, penetrating violence, and operations have occurred over 15 years. These changes will have profound effects on the practice of trauma surgeons and on surgical education.


Assuntos
Competência Clínica , Cirurgia Geral/educação , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Centros de Traumatologia/tendências , Ferimentos e Lesões/cirurgia , Traumatismos Abdominais/diagnóstico , Acidentes de Trânsito/estatística & dados numéricos , Adulto , California/epidemiologia , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Admissão do Paciente , Estudos Retrospectivos , Índices de Gravidade do Trauma , Violência/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia
17.
FASEB J ; 15(14): 2718-20, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11606476

RESUMO

Chronic stimulation of cardiac beta1-adrenergic receptors contributes to disease progression and mortality in patients and animal models of heart failure. To search for the mechanism of adrenergic impairment of cardiac function in vivo, we studied transgenic mice with cardiac-specific overexpression of beta1-adrenergic receptors. Transgenic mice with cardiac overexpression of beta1-adrenergic receptors showed progressive left ventricular fibrosis starting at 4 months of age. Left ventricular catheterization revealed a modest enhancement of contractility and relaxation at 2 months of age, followed by progressive dysfunction in both parameters and ultimately cardiac failure. When the effects of endogenous catecholamines were blocked by the b-receptor antagonist propranolol, maximal rate of contractility (dp/dtmax) and maximal rate of relaxation (dp/dtmin) were significantly blunted in 2-month-old beta1-receptor transgenic mice. Isolated cardiomyocytes from these animals displayed markedly altered calcium transients with significant prolongation of the intracellular calcium transient compared with nontransgenic littermates. We determined the expression of sarcoplasmic reticulum proteins involved in calcium handling by RNase protection assay and by immunoblotting. Although the expression of calsequestrin, triadin, and phospholamban was not altered, we observed a progressive decrease in junctin abundance in beta1-receptor transgenic mice (Pbeta1-adrenergic receptors.


Assuntos
Cálcio/metabolismo , Proteínas de Membrana , Oxigenases de Função Mista , Miocárdio/metabolismo , Receptores Adrenérgicos beta 1/genética , Animais , Pressão Sanguínea/fisiologia , Western Blotting , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , ATPases Transportadoras de Cálcio/genética , ATPases Transportadoras de Cálcio/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Regulação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Camundongos , Camundongos Transgênicos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Contração Miocárdica/fisiologia , Miocárdio/citologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Adrenérgicos beta 1/fisiologia , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Fatores de Tempo
18.
Mol Pharmacol ; 60(4): 712-7, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11562432

RESUMO

We tested the hypothesis that the human beta(1)-adrenergic receptor displays constitutive activity and that beta-adrenergic antagonists differ in their ability to modulate this constitutive activity. Transfection of the cDNAs of the human beta(1)- and beta(2)-adrenergic receptors into COS-7 cells caused increases in basal cAMP that were proportional to the receptor levels, thus demonstrating constitutive activity for both subtypes. At comparable receptor levels, the increase in basal cAMP was about 5-fold higher for the beta(2)- than for the beta(1)-subtype. As a model for enhanced beta-adrenergic signaling at the whole-organ level, we used transgenic mice with heart-specific overexpression of the human beta(1)-adrenergic receptor. In this model, the beta(1)-adrenergic receptor displayed constitutive activity as evidenced by a higher spontaneous beating rate of isolated right atria from beta(1)-transgenic versus wild-type mice. This difference was abolished by the addition of CGP20712A, demonstrating inverse agonist properties of this compound. We then tested whether various beta-adrenergic antagonists currently in clinical use for the treatment of heart failure differ in their ability to modulate constitutive activity of the cardiac beta(1)-adrenergic receptor. The beta(1)-selective antagonists metoprolol and bisoprolol showed significant inverse agonist activity at the beta(1)-adrenergic receptor. Carvedilol behaved as a neutral antagonist and xamoterol displayed marked partial agonist activity. We conclude that the human beta(1)-adrenergic receptor displays constitutive activity that is considerably lower than that of the beta(2)-subtype. beta-Adrenergic antagonists currently in clinical use differ in their ability to exert inverse agonist activity at the human beta(1)-adrenergic receptor, which may contribute to their therapeutic effects.


Assuntos
Miocárdio/metabolismo , Receptores Adrenérgicos beta 1/metabolismo , Antagonistas Adrenérgicos/farmacologia , Animais , Células COS , Coração/efeitos dos fármacos , Humanos , Camundongos , Camundongos Transgênicos , Receptores Adrenérgicos beta 1/efeitos dos fármacos , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Transfecção
19.
Arch Surg ; 136(5): 513-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11343541

RESUMO

HYPOTHESIS: It is possible to quantify an amount of thoracic hemorrhage, after blunt and penetrating injury, at which delay of thoracotomy is associated with increased mortality. DESIGN: A retrospective case series. SETTING: Five urban trauma centers. STUDY SELECTION: Patients undergoing urgent thoracotomy (within 48 hours of injury) for hemorrhage (excluding emergency department thoracotomy). DATA EXTRACTION: Respective registries identified patients who underwent urgent thoracotomy. Injury characteristics, initial and subsequent chest tube outputs, time before thoracotomy, and outcomes were evaluated. MAIN OUTCOME MEASURE: Death. RESULTS: One hundred fifty-seven patients (36 with blunt and 121 with penetrating injuries) underwent urgent thoracotomy for hemorrhage between January 1, 1995, and December 31, 1998. Mortality correlated with mean (+/- SD) Injury Severity Score (38 +/- 19 vs 22 +/- 12.6 for survivors; P<.01) and mechanism (24 [67%] for blunt vs 21 [17%] for penetrating injuries; P<.01). Mortality increased as total chest blood loss increased, with the risk for death at blood loss of 1500 mL being 3 times greater than at 500 mL. Blunt-injured patients waited a significantly longer time to thoracotomy than penetrating-injured patients (4.4 +/- 9.0 h vs 1.6 +/- 3.0 h; P =.02) and also had a greater total chest tube output before thoracotomy (2220 +/- 1235 mL vs 1438 +/- 747 mL; P =.001). CONCLUSIONS: The risk for death increases linearly with total chest hemorrhage after thoracic injury. Thoracotomy is indicated when total chest tube output exceeds 1500 mL within 24 hours, regardless of injury mechanism.


Assuntos
Serviços Médicos de Emergência , Hemorragia/cirurgia , Traumatismos Torácicos/cirurgia , Toracotomia , Adulto , Feminino , Humanos , Intubação Intratraqueal , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ferimentos não Penetrantes/cirurgia , Ferimentos Penetrantes/cirurgia
20.
Am J Orthop (Belle Mead NJ) ; 30(5): 426-7, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11370951

RESUMO

Necrotizing fasciitis is a limb- and life-threatening soft-tissue infection that frequently involves the extremities. This article describes the first case of necrotizing fasciitis developing from a single steroid injection of the greater trochanteric bursa. Despite early resuscitation and aggressive surgical management that included a hip disarticulation, the patient expired. Potential contributing factors are reviewed.


Assuntos
Corticosteroides/efeitos adversos , Fasciite Necrosante/etiologia , Idoso , Bolsa Sinovial , Bursite/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Fasciite Necrosante/terapia , Fêmur , Humanos , Injeções Intra-Articulares/efeitos adversos , Pneumopatias Obstrutivas/complicações , Masculino , Obesidade/complicações
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