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1.
J Crit Care ; 72: 154162, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36219946

RESUMO

PURPOSE: The aim was to verify the impact of obesity on the long-term outcome of patients with severe SARS-CoV-2 ARDS. MATERIALS AND METHODS: The retrospective study included patients admitted to the high-volume ECMO centre between March 2020 and March 2022. The impact of body mass index (BMI), co-morbidities and therapeutic measures on the short and 90-day outcomes was analysed. RESULTS: 292 patients were included, of whom 119(40.8%) were treated with veno-venous ECMO cannulated mostly (73%) in a local hospital. 58.5% were obese (64.7% on ECMO), the ECMO was most frequent in BMI > 40(49%). The ICU mortality (36.8% for obese vs 33.9% for the non-obese, p = 0.58) was related to ECMO only for the non-obese (p = 0.04). The 90-day mortalities (48.5% obese vs 45.5% non-obese, p = 0.603) of the ECMO and non-ECMO patients were not significantly influenced by BMI (p = 0.47, p = 0.771, respectively). The obesity associated risk factors for adverse outcome were age <50 (RR 2.14) and history of chronic immunosuppressive therapy (RR 2.11, p = 0.009). The higher dosage of steroids (RR 0.57, p = 0.05) associated with a better outcome. CONCLUSIONS: The high incidence of obesity was not associated with worse short and long-term outcomes. ECMO in obese patients together with the use of steroids in the later stage of ARDS may improve survival.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , SARS-CoV-2 , Estudos Retrospectivos , COVID-19/terapia , Síndrome do Desconforto Respiratório/terapia , Obesidade/complicações , Corticosteroides/uso terapêutico
2.
J Radiol Prot ; 41(4)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34673554

RESUMO

In 2021, the ICRP initiated the revision of the general recommendations of the system of radiation protection, and part of it will focus on dose quantities. The recently published ICRP Publication 147 and ICRU Report 95 have described the extent of the proposed modifications and paved the way for the strategy to be adopted. These revisions would seek to simplify, improve the accuracy and extend the field of use of dose quantities. While the Radiological Protection Working Group of the World Nuclear Association recognises the notable improvement in the estimation of the protection quantities and the usefulness of such changes for the medical and research sector, the benefits of the proposed new system seem very limited for the nuclear industry and industries involving naturally occurring radioactive materials. The complexity associated with changing a long-standing and robust system and the risk incurred by the human factor seem unjustified, bearing in mind the likely cost.


Assuntos
Proteção Radiológica , Humanos , Doses de Radiação
3.
J Radiol Prot ; 41(4)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34343979

RESUMO

Low dose radiation has been widely accepted by the radiation protection community as presenting a very low risk to human health, if any. Over-conservatism in optimisation principles and regulations have resulted in a disproportionate fear of radiation amongst the general public and government authorities alike, overlooking the great benefits nuclear science and techniques have brought to society as a whole. As such, the World Nuclear Association advocates for a recontextualisation of the radiation hazards with regards to low dose radiation, and a greater awareness as to the absence of any discernible effects associated with it.


Assuntos
Proteção Radiológica , Humanos , Doses de Radiação
4.
Physiol Res ; 69(4): 621-631, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32584133

RESUMO

Chronic inflammation of adipose tissue is associated with the pathogenesis of cardiovascular diseases. Mast cells represent an important component of the innate defense system of the organism. In our work, we quantified mast cell number in epicardial adipose tissue (EAT), subcutaneous adipose tissue (SAT), and right atrial myocardium (RA) in patients undergoing open heart surgery (n=57). Bioptic samples of EAT (n=44), SAT (n=42) and RA (n=17) were fixed by 4 % paraformaldehyde and embedded into paraffin. An anti-mast cell tryptase antibody was used for immunohistochemical detection and quantification of mast cells. We also demonstrated immunohistochemically the expression of CD117 and chymase markers. In EAT of patients with coronary artery disease (CAD), higher incidence of mast cells has been found compared to patients without CAD (3.7±2.6 vs. 2.1±1.2 cells/mm(2)). In SAT and RA, there was no difference in the number of mast cells in CAD and non-CAD patients. Mast cells in SAT, EAT and RA expressed CD117 and chymase. An increased incidence of mast cells in EAT of CAD patients may indicate the specific role of these inflammatory cells in relation to EAT and coronary arteries affected by atherosclerosis.


Assuntos
Tecido Adiposo/patologia , Doença da Artéria Coronariana/patologia , Inflamação/patologia , Mastócitos/patologia , Pericárdio/patologia , Tecido Adiposo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Doença da Artéria Coronariana/metabolismo , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Mastócitos/metabolismo , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Pericárdio/metabolismo
5.
Physiol Res ; 67(6): 881-890, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30204471

RESUMO

Omentin is a protein produced by numerous tissues including adipose tissue. Its concentrations are decreased in patients with obesity, type 2 diabetes mellitus (DM) and coronary artery disease (CAD). Experimental studies suggest that omentin may have anti-inflammatory and insulin-sensitizing properties. In the present study, we measured circulating omentin levels and its mRNA expression in epicardial and subcutaneous fat, intercostal and heart muscle before and after elective cardiac surgery in patients with CAD (CAD+, DM-, n=18), combination of CAD and DM (CAD+, DM+, n=9) or with none of these conditions (CAD-, DM-, n=11). The groups did not differ in baseline anthropometric and biochemical characteristics with the exception of higher blood glucose and HBA(1c) in CAD+, DM+ group. Baseline circulating omentin levels tended to be lower in CAD+, DM- and CAD+, DM+ groups as compared to CAD-, DM- group and cardiac surgery increased its concentration only in CAD-, DM- group. The change in serum omentin levels during surgery inversely correlated with epicardial fat thickness. While baseline omentin mRNA expression did not differ among the groups in any of the studied tissues, its increase after surgery was present only in subcutaneous fat in CAD-, DM- and CAD+, DM- groups, but not in CAD+, DM+ group. Intercostal muscle omentin mRNA expression increased after surgery only in CAD-, DM- group. In conclusion, cardiac surgery differentially affects omentin levels and subcutaneous fat and skeletal muscle mRNA expression in patients without coronary artery disease and diabetes as compared to patients with these conditions.


Assuntos
Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/sangue , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Procedimentos Cirúrgicos Eletivos , Lectinas/sangue , RNA Mensageiro/sangue , Adulto , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/cirurgia , Citocinas/genética , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/genética , Expressão Gênica , Humanos , Lectinas/genética , Masculino , Pessoa de Meia-Idade , Pericárdio/metabolismo , RNA Mensageiro/genética
6.
Trop Anim Health Prod ; 50(7): 1519-1527, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29687217

RESUMO

As in other sub-Saharan African countries, purebred dairy genetics such as Holsteins were imported to Malawi. The study investigated their economic performance by comparing them with local Zebu-crossbreds based on 131 smallholder dairy farm observations from Southern Malawi. High-yielding purebred cows and crossbred cows showed no significant differences in lactation yield and calving interval. Looking at the farms' actual costs, by-products such as maize bran clearly dominated the cost structure for both breeds, but crossbreeds showed significantly lower concentrate costs. While there was no statistically significant difference in income for both breed types, a substantial share (23%) of farms under investigation shows negative incomes. Based on survey data, two typical farms were established representing standard costs with homogenous assumptions such as identical milk price. The comparison of typical farms covering the full dairy system clearly indicated that crossbred dairy cows outperformed purebreds. In addition, a simulation of a shorter calving interval for both typical farms revealed a substantial positive impact on income for both breed types with more than 30% increase. We conclude that focusing on crossbreds in combination with improved feeding and fertility management offers a more promising strategy for smallholder dairy farms in Southern Malawi than just acquiring high-yielding purebreds.


Assuntos
Cruzamento , Indústria de Laticínios/economia , Reprodução , África do Norte , Animais , Bovinos , Comércio , Custos e Análise de Custo , Fazendas , Feminino , Fertilidade , Lactação , Malaui , Leite/química , Especificidade da Espécie
7.
Perfusion ; 30(7): 520-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25258197

RESUMO

OBJECTIVES: There is some controversy as to whether there is a benefit from the use of a centrifugal pump compared with a roller pump during cardiopulmonary bypass to facilitate cardiac surgery. We compared the two pumps, with the primary aim of determining any difference in the effects on inflammation after pulmonary endarterectomy surgery which required prolonged cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Between September 2010 and July 2013, 58 elective patients undergoing pulmonary endarterectomy were included in this prospective, randomised, controlled study; 30 patients were randomly allocated to the control group, which used a roller pump, and 28 patients to the treatment group, which used a centrifugal pump. Interleukin-6, procalcitonin, C-reactive protein, thromboelastographic parameters, P-selectin, international normalised ratio, activated prothrombin time, free haemoglobin, haematocrit, red blood cell count, white blood cell count, platelet count and protein S100ß were recorded during and after the procedure. We also recorded the length of intensive care unit stay, blood loss and transfusion, neurological outcomes and respiratory and renal failure. RESULTS: There was a significant difference in the primary outcome measure: Interleukin-6 was significantly higher in the roller pump group (587 ± 38 ng · l(-1) vs. 327 ± 37 ng · l(-1); p<0.001) 24 hours after surgery, which we interpreted as an increased inflammatory response. This was confirmed by a significant rise in the procalcitonin level in the roller pump group 48 hours following surgery (0.79 (0.08-25.25) ng · ml(-1) vs. 0.36 (0.02-5.83) ng · ml(-1); p<0.05). There were, however, no significant differences in clinical outcome data. CONCLUSIONS: We have shown that the use of a centrifugal pump during prolonged cardiopulmonary bypass and deep hypothermic circulatory arrest is associated with a reduced inflammatory response compared to the standard roller pump. Larger multi-centre trials in this area of practice are required.


Assuntos
Ponte Cardiopulmonar/instrumentação , Ponte Cardiopulmonar/métodos , Coração Auxiliar , Adulto , Proteínas Sanguíneas/metabolismo , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade
8.
Int J Obes (Lond) ; 38(5): 746-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24100424

RESUMO

Telomere length can be considered as a biological marker for cell proliferation and aging. Obesity is associated with adipocyte hypertrophy and proliferation as well as with shorter telomeres in adipose tissue. As adipose tissue is a mixture of different cell types and the cellular composition of adipose tissue changes with obesity, it is unclear what determines telomere length of whole adipose tissue. We aimed to investigate telomere length in whole adipose tissue and isolated adipocytes in relation to adiposity, adipocyte hypertrophy and adipose tissue inflammation and fibrosis. Telomere length was measured by real-time PCR in visceral adipose tissue, and isolated adipocytes of 21 obese women with a waist ranging from 110 to 147 cm and age from 31 to 61 years. Telomere length in adipocytes was shorter than in whole adipose tissue. Telomere length of adipocytes but not whole adipose tissue correlated negatively with waist and adipocyte size, which was still significant after correction for age. Telomere length of whole adipose tissue associated negatively with fibrosis as determined by collagen content. Thus, in extremely obese individuals, adipocyte telomere length is a marker of adiposity, whereas whole adipose tissue telomere length reflects the extent of fibrosis and may indicate adipose tissue dysfunction.


Assuntos
Fibrose/patologia , Gordura Intra-Abdominal/patologia , Obesidade Mórbida/patologia , Adipócitos/ultraestrutura , Adulto , Feminino , Fibrose/genética , Humanos , Hipertrofia , Pessoa de Meia-Idade , Obesidade Mórbida/genética , Reação em Cadeia da Polimerase em Tempo Real , Telômero/ultraestrutura
9.
Physiol Res ; 63(1): 83-94, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24182337

RESUMO

Adipocyte fatty acid binding protein (A-FABP) is a novel adipokine involved in the regulation of lipid and glucose metabolism and inflammation. To evaluate its potential role in the development of postoperative hyperglycemia and insulin resistance we assessed A-FABP serum concentrations and mRNA expression in skeletal and myocardial muscle, subcutaneous and epicardial adipose tissue and peripheral monocytes in 11 diabetic and 20 age- and sex-matched non-diabetic patients undergoing elective cardiac surgery. Baseline serum A-FABP did not differ between the groups (31.1+/-5.1 vs. 25.9+/-4.6 ng/ml, p=0.175). Cardiac surgery markedly increased serum A-FABP in both groups with a rapid peak at the end of surgery followed by a gradual decrease to baseline values during the next 48 h with no significant difference between the groups at any timepoint. These trends were analogous to postoperative excursions of plasma glucose, insulin and selected proinflammatory markers. Cardiac surgery increased A-FABP mRNA expression in peripheral monocytes, while no effect was observed in adipose tissue or muscle. Our data suggest that circulating A-FABP might be involved in the development of acute perioperative stress response, insulin resistance and hyperglycemia of critically ill irrespectively of the presence of diabetes mellitus.


Assuntos
Tecido Adiposo/metabolismo , Procedimentos Cirúrgicos Cardíacos , Proteínas de Ligação a Ácido Graxo/biossíntese , Monócitos/metabolismo , RNA Mensageiro/biossíntese , Idoso , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade
10.
Prague Med Rep ; 114(1): 9-17, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23547721

RESUMO

The incidence of post infarction ventricular septal rupture (PIVSR) is decreasing in the last years due to aggressive treatment of myocardial infarction with early percutaneous coronary interventions. As a consequence patients with PIVSR are referred to surgery more often with significant heart failure. The aim of this retrospective study was to assess the influence of these on the operative results and to identify the risk factors of operative mortality. A retrospective analysis of prospectively collected data of patients with the PIVSR admitted to our center from November 2004 to February 2012 was performed. Variables were analyzed using two-dimensional correspondence analysis. There were 25 patients (12 males and 13 females) with mean age 70.2 years (47-82) operated on; 17 (68%) presented with anterior and 8 (32%) with posterior PIVSR. Eighteen patients (72%) had acute heart failure, 13 (52%) presented with cardiogenic shock. Before surgery, intraaortic balloon pump (IABP) had 20 (80%) patients; in 4 (16%) a ventricular assist device was used, either Extracorporeal Membrane Oxygenation (ECMO) or centrifugal pumps as biventricular assist. Operative mortality was 40% (10 pts.). Four patients (12%) had small non-significant recurrent shunt on postoperative echocardiography. Although majority of patients with PIVSR have significant heart failure prior to surgery the operative mortality remains comparable to older studies. Predictors of perioperative death were concomitant surgical reconstruction of the left ventricle, renal impairment before operation, male gender, history of coronary artery disease, PIVSR location posterior, and shock at surgery.


Assuntos
Ruptura do Septo Ventricular/cirurgia , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Prague Med Rep ; 113(4): 299-302, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23249662

RESUMO

The authors present a case of massive lung bleeding following pulmonary endarterectomy (PEA) that was treated with peripheral veno-venous extracorporeal membrane oxygenation (VV ECMO). The patient repeatedly underwent bronchoscopy for airway blood clot obstruction and finally was successfully weaned off the support. The authors discuss the indications for ECMO in treatment of the most serious complications following PEA, and emphasize the importance of echocardiographic evaluation of the right ventricular function in relation to the indicated type of extracorporeal support. Anticoagulation strategy for patients shortly after the major surgery connected to ECMO is also discussed.


Assuntos
Endarterectomia , Oxigenação por Membrana Extracorpórea , Hemorragia Pós-Operatória/terapia , Artéria Pulmonar/cirurgia , Endarterectomia/efeitos adversos , Feminino , Humanos , Hipertensão Pulmonar/cirurgia , Pessoa de Meia-Idade
12.
J Cardiovasc Surg (Torino) ; 52(3): 445-51, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21577197

RESUMO

Extracorporeal membrane oxygenation (ECMO) is an established rescue treatment option for severe respiratory and cardiac failure in infants and neonates and has recently become widely utilised in adults. ECMO support can be initiated rapidly in an emergency setting both by percutanous implantation and surgically; it allows transportation of patients in cardio-pulmonary collapse and bridging of critically ill patients to be recovered, other support measures or transplantation. The aim of this study was to report authors' initial experience after starting an ECMO program in a university-based cardiac center. The institutionally approved ECMO team bears responsibility for adjudication regarding indication and implementation of ECMO in all patients. Since the establishment of the ECMO team in October 2007, one elective and nine urgent patients in deep cardiogenic and/or ventilatory collapse were treated by ECMO support up to December 2008. Three patients suffered severe acute right heart dysfunction, two patients suffered postcardiotomy refractory cardiogenic shock, two patients had a cardiogenic shock due to postinfarction interventricular septal rupture, two patients experienced severe respiratory failure and one had elective ECMO implantation as a back-up support during high-risk percutaneous coronary intervention. Veno-arterial ECMO was used in eight cases and veno-venous in two cases of isolated respiratory failure. In nine patients, ECMO circuit was instituted by peripheral cannulation, in eight out of nine cases by percutaneous puncture. On one occasion central surgical cannulation was used. In urgent patients, immediate hemodynamic and oxygenation improvement was observed. Average support duration was 6.8 days (range 1-16 days). Five (50 %) patients were successfully weaned from ECMO and survived to hospital discharge. The illness severity in urgent patients defined by SOFA score ranged from 10 to 17, patients dying while on ECMO had higher SOFA scores (14.8±1.6 vs. 10.8±1.5; P=0.0065). Complications included mainly bleeding. ECMO support allows treatment of severely ill patients in imminent cardiovascular and/or ventilatory collapse. Therefore, establishment of an ECMO program in university affiliated cardiac center is fully justified. A multidisciplinary approach is essential. Despite adequate training and education of ECMO team members, this highly invasive therapeutic modality bears an inherent risk of complications.


Assuntos
Oxigenação por Membrana Extracorpórea , Cardiopatias/terapia , Hospitais de Ensino , Insuficiência Respiratória/terapia , Adulto , Idoso , Estado Terminal , República Tcheca , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Cardiopatias/etiologia , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Avaliação de Programas e Projetos de Saúde , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
14.
J Cardiovasc Surg (Torino) ; 49(3): 381-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18446125

RESUMO

AIM: The aim of this retrospective study was to evaluate the effectiveness of Terlipressin in the treatment of severe hypotension in cardiosurgical patients and to assess the differences between the groups of survivors and nonsurvivors. METHODS: The study population was 27 patients who developed hypotension after cardiac surgery. RESULTS: All surviving patients developed refractory hypotension early after extracorporeal circulation. Of the 9 nonsurvivors, 3 also experienced postcardiotomy hypotension, while the remaining 6 developed severe hypotension during sepsis. Terlipressin given continuously significantly increased the mean arterial pressure and reduced the heart rate in both groups. Norepinephrine requirements decreased significantly among survivors only. The mean pulmonary artery pressure and pulmonary capillary wedge pressure levels remained unchanged or increased insignificantly, while several liver markers in the survivor group significantly increased. CONCLUSION: Terlipressin given continuously is a potent vasopressor in patients with norepinephrine-resistant postcardiotomy hypotension; however, Terlipressin treatment failed in patients who developed refractory hypotension during sepsis. We cannot recommend this therapy in such patients as it proved to be hemodynamicaly ineffective and may even worsen the circulatory situation.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Hipotensão/tratamento farmacológico , Lipressina/análogos & derivados , Vasoconstritores/uso terapêutico , Idoso , Análise de Variância , Distribuição de Qui-Quadrado , Feminino , Humanos , Hipotensão/etiologia , Infusões Intravenosas , Lipressina/administração & dosagem , Lipressina/uso terapêutico , Masculino , Estudos Retrospectivos , Estatísticas não Paramétricas , Sobreviventes , Terlipressina , Resultado do Tratamento , Vasoconstritores/administração & dosagem
15.
Cas Lek Cesk ; 146(4): 396-400, 2007.
Artigo em Tcheco | MEDLINE | ID: mdl-17491250

RESUMO

BACKGROUND: During gravidity changes in coagulation develop, however different norms for pregnant women and prevailing population are rarely used. Pathological gravidity can be accompanied with more significant coagulopathies. Thrombelastography is more and more frequently used for evaluation of coagulation parameters of pregnant women. The aim of the study was to compare thrombelastographic coagulation parameters in females with physiological or pathological gravidity and with norms for prevailing population. METHODS AND RESULTS: 60 women in the 3rd trimester of physiological gravidity (group ZDRAVE) and 50 women with pathological gravidity (women with preeclampsia or with a dead fetus, group PATOL) were examined. Both groups were of the comparable age. Average values of studied parameters in the group ZDRAVE were found at the level of "procoagulation" limits for prevailing population. In the group PATOL, average values were even more "procoagulative", however, differences to the ZDRAVE group were nor significant: time r 4.7 (SD 1.7) vs. 4.4 (SD 2.0) p = 0.461 (norm for prevailing population 4-8 min), time to 1.5 (0.5) vs. 1.3 (0.4) p = 0.030 (norm 1-4 min), angle alpha 69.6 (5.5) vs. 71.0 (7.7) p = 0.324 (norm 47-74 degrees), maximal amplitude 71.3 (4.5) vs. 73.1 (4.7) p = 0.079 (norm 55-73 mm), coagulation index 2.7 (1.8) vs. 3.2 (1.8) p = 0.219 (norm (-3)-(+3)). In the group PATOL higher variability than in the group ZDRAVE was found. On the basis of the group ZDRAVE selection percentiles, new norms of thrombelastographic coagulation parameters for pregnant women were elaborated. CONCLUSIONS: Coagulation during pregnancy differs significantly from that of prevailing population. That is why the new thrombelastographic norms for pregnant women are submitted. Coagulation changes in pathological pregnancies are more difficult to anticipate than in healthy gestations.


Assuntos
Coagulação Sanguínea , Pré-Eclâmpsia/sangue , Gravidez/sangue , Tromboelastografia , Adulto , Feminino , Humanos , Valores de Referência
16.
Clin Infect Dis ; 42(4): 548-58, 2006 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-16421800

RESUMO

BACKGROUND: Bacille Calmette-Guérin (BCG)--a live, attenuated vaccine--is routinely given to neonates in settings where tuberculosis is endemic, irrespective of human immunodeficiency virus (HIV) exposure. HIV-infected infants and other immunodeficient infants are at risk of BCG-related complications. We report the presentation, treatment, and mortality of children who develop BCG disease, with emphasis on HIV-infected children. In addition, we present a revised classification of BCG disease in children and propose standard diagnostic and management guidelines. METHODS: This retrospective, hospital-based study was conducted in the Western Cape Province, South Africa. Mycobacterium tuberculosis complex isolates recovered from children aged <13 years during the period of August 2002 through January 2005 were speciated by polymerase chain reaction to confirm Mycobacterium bovis BCG. Clinical data were collected through medical file review. BCG disease was classified according to standard and revised disease classifications. Mortality was assessed at the end of the study period. RESULTS: BCG disease was diagnosed in 25 children; 22 (88%) had local disease, and 8 (32%) had distant or disseminated disease; 5 children (20%) had both local and distant or disseminated disease. Seventeen children were HIV infected; 2 children had other immunodeficiencies. All 8 children with distant or disseminated disease were immunodeficient; 6 were HIV infected. The mortality rate was 75% for children with distant or disseminated disease. CONCLUSIONS: BCG vaccination poses a risk to infants perinatally infected with HIV and to other primary immunodeficient children. The proposed pediatric BCG disease classification reflects clinically relevant disease categories in HIV-infected children. The suggested diagnostic and treatment guidelines should improve existing case management and surveillance. Prospective evaluation of management strategies for BCG disease in HIV-infected and HIV-uninfected children is essential.


Assuntos
Vacina BCG/efeitos adversos , Infecções por HIV/imunologia , Mycobacterium bovis , Tuberculose/classificação , Tuberculose/etiologia , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Antituberculosos/uso terapêutico , Criança , Pré-Escolar , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico
17.
J Neurophysiol ; 82(6): 2936-46, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10601430

RESUMO

A quantitative analysis of activity-related calcium dynamics was performed in motoneurons of the nucleus hypoglossus in the brain stem slice preparation from mouse by simultaneous patch-clamp and microfluorometric calcium measurements. Motoneurons were analyzed under in vitro conditions that kept them in a functionally intact state represented by rhythmic, inspiratory-related bursts of excitatory postsynaptic currents and associated action potential discharges. Bursts of electrical activity were paralleled by somatic calcium transients resulting from calcium influx through voltage-activated calcium channels, where each action potential accounted for a calcium-mediated charge influx around 2 pC into the somatic compartment. Under in vivo conditions, rhythmic-respiratory activity in young mice occurred at frequencies up to 5 Hz, demonstrating the necessity for rapid calcium elevation and recovery in respiratory-related neurons. The quantitative analysis of hypoglossal calcium homeostasis identified an average extrusion rate, but an exceptionally low endogenous calcium binding capacity as cellular parameters accounting for rapid calcium signaling. Our results suggest that dynamics of somatic calcium transients 1) define an upper limit for the maximum frequency of respiratory-related burst discharges and 2) represent a potentially dangerous determinant of intracellular calcium profiles during pathophysiological and/or excitotoxic conditions.


Assuntos
Cálcio/fisiologia , Nervo Hipoglosso/fisiologia , Neurônios Motores/fisiologia , Algoritmos , Animais , Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Eletrofisiologia , Corantes Fluorescentes , Fluorometria , Fura-2 , Homeostase/fisiologia , Nervo Hipoglosso/citologia , Técnicas In Vitro , Potenciais da Membrana/fisiologia , Camundongos , Técnicas de Patch-Clamp , Mecânica Respiratória/fisiologia , Medula Espinal/citologia , Medula Espinal/fisiologia
18.
J Physiol ; 520 Pt 2: 485-502, 1999 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-10523417

RESUMO

1. A quantitative analysis of endogenous calcium homeostasis was performed on 65 motoneurones in slices of the lumbar spinal cord from 2- to 8-day-old mice by simultaneous patch-clamp and microfluorometric calcium measurements. 2. Somatic calcium concentrations were monitored with a temporal resolution in the millisecond time domain. Measurements were performed by using a monochromator for excitation and a photomultiplier detection system. 3. Somatic calcium signalling was investigated during defined voltage-clamp protocols. Calcium responses were observed for membrane depolarizations positive to -50 mV. A linear relation between depolarization time and free calcium concentrations ([Ca2+]i) indicated that voltage-dependent calcium influx dominated the response. 4. Endogenous calcium homeostasis was quantified by using the 'added buffer' approach. In the presence of fura-2 and mag-fura-5, calcium transients decayed according to a monoexponential function. Decay-time constants showed a linear dependence on dye concentration and the extrapolated constant in the absence of indicator dye was 371 +/- 120 ms (n = 13 cells, 21 C). 5. For moderate elevations (< 1 microM), recovery kinetics of depolarization-induced calcium transients were characterized by a calcium-independent, 'effective' extrusion rate gamma = 140 +/- 47 s-1 (n = 13 cells, 21 C). 6. The endogenous calcium binding ratio for fixed buffers in spinal motoneurones was kappaB' = 50 +/- 17 (n = 13 cells), indicating that less than 2 % of cytosolic calcium ions contributed to [Ca2+]i. 7. Endogenous binding ratios in spinal motoneurones were small compared to those found in hippocampal or cerebellar Purkinje neurones. From a functional perspective, they provided motoneurones with rapid dynamics of cytosolic [Ca2+]i for a given set of influx, extrusion and uptake mechanisms. 8. With respect to pathophysiological conditions, our measurements are in agreement with a model where the selective vulnerability of spinal motoneurones during excitotoxic conditions and motoneurone disease partially results from low endogenous calcium buffering.


Assuntos
Cálcio/metabolismo , Neurônios Motores/metabolismo , Medula Espinal/metabolismo , Animais , Canais de Cálcio/metabolismo , Fluorometria , Fura-2/análogos & derivados , Homeostase , Camundongos , Doença dos Neurônios Motores/metabolismo , Técnicas de Patch-Clamp , Ligação Proteica , Células de Purkinje/metabolismo
19.
J Physiol ; 511 ( Pt 1): 105-17, 1998 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-9679167

RESUMO

1. Simultaneous patch clamp and rapid microfluorometric calcium measurements were performed on sixty-five motoneurones in slices of the nucleus hypoglossus in the brainstem of 2- to 6-day-old mice. 2. Hypoglossal motoneurones were particularly vulnerable to mechanical or metabolic stress during isolation of in vitro slice preparations. Therefore, experimental conditions were optimized for functional integrity, as judged by spontaneous rhythmic activity of hypoglossal nerves (XII). 3. Calcium concentrations in the cell soma were monitored with a temporal resolution in the millisecond time domain during depolarizing voltage steps. Ratiometric fluorescence measurements were made using a rapid monochromator (switching tau < 10 ms), a photomultiplier tube and the calcium sensitive dyes fura-2 and mag-fura-5. 4. Dynamics of somatic calcium transients were investigated as a function of the concentration of calcium indicator dye in the cell. Decays of calcium transients were approximated to a single exponential component and decay time constants showed a linear dependence on dye concentration. The extrapolated decay time in the absence of indicator dye was 0.7 +/- 0.2 s, suggesting rapid somatic calcium dynamics under physiological conditions. 5. By a process of back-extrapolation, the 'added buffer' method, a calcium binding ratio of 41 +/- 12 (9 cells) was obtained indicating that 98% of the calcium ions entering a hypoglossal motoneurone were bound by endogenous buffers. 6. Endogenous calcium binding ratios in hypoglossal motoneurones were small compared with those of other neurones with comparable size or geometry. Accordingly, our measurements suggest that the selective vulnerability of hypoglossal motoneurones to calcium-related excitotoxicity might partially result from low concentrations of calcium buffers in these cells.


Assuntos
Tronco Encefálico/fisiologia , Cálcio/metabolismo , Nervo Hipoglosso/fisiologia , Neurônios Motores/fisiologia , Medula Espinal/fisiologia , Animais , Fura-2 , Técnicas In Vitro , Cinética , Potenciais da Membrana , Camundongos , Técnicas de Patch-Clamp , Espectrometria de Fluorescência , Fatores de Tempo , Nervo Vago/fisiologia
20.
Neuroreport ; 6(13): 1729-32, 1995 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-8541469

RESUMO

Neuronal connectivity of brain areas involved in song learning and song production was studied in the in vitro slice preparation of the zebra finch brain by electrophysiological intracellular recording techniques and by micro-injections of the fluorescent tracer tetramethyl-rhodamine-dextran-amine. While validating some of the known projections to be preserved in the in vitro slice preparation, we were also able to identify a new projection from neurones of the lateral portion of the magnocellular nucleus of the anterior neostriatum towards area X of the lobus parolfactorius.


Assuntos
Aves/fisiologia , Neostriado/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Núcleos Talâmicos/fisiologia , Vocalização Animal/fisiologia , Animais , Dextranos , Corantes Fluorescentes , Técnicas In Vitro , Masculino , Neostriado/citologia , Reprodutibilidade dos Testes , Rodaminas
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