Contractile effects of stimulation of D1-dopamine receptors in the isolated human atrium.

Dopamine receptors have been claimed not to directly increase contractility in the human heart. Therefore, we performed contraction experiments in isolated electrically driven human atrial preparations (HAP). For comparison, we performed contraction experiments with left atrial preparations of transgenic mice which harbor a cardiac overexpression of human D1-dopamine receptors (D1-TG). In D1-TG, first we noted that dopamine (10 nM-10 µM cumulatively applied) in the presence of propranolol exerted a concentration- and time-dependent positive inotropic effect in D1-TG. In a similar fashion, dopamine increased force of contraction in the presence of 0.4 µM propranolol in HAP and these effects were amplified by pre-treatment with inhibitor of phosphodiesterase III (1 µM) cilostamide. Moreover, contractile effects of dopamine in the presence of propranolol 0.4 µM in HAP were antagonized by odapipam, haloperidol, or raclopride. Ten micromolars of fenoldopam in the presence of cilostamide increased force of contraction in HAP and this effect was antagonized by SCH 23390. We conclude that stimulation of human D1-dopamine receptors can increase force of contraction in the HAP.

Evaluation of the inflammation-based modified Glasgow Prognostic Score (mGPS) as a prognostic and predictive biomarker in patients with metastatic colorectal cancer receiving first-line chemotherapy: a post hoc analysis of the randomized phase III XELAVIRI trial (AIO KRK0110).

BACKGROUND: The inflammation-based modified Glasgow Prognostic Score (mGPS) combines serum levels of C-reactive protein and albumin and was shown to predict survival in advanced cancer. We aimed to elucidate the prognostic impact of mGPS on survival as well as its predictive value when combined with gender in unselected metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the randomized phase III XELAVIRI trial. PATIENTS AND METHODS: In XELAVIRI, mCRC patients were treated with either fluoropyrimidine/bevacizumab followed by additional irinotecan at first progression (sequential treatment arm; Arm A) or upfront combination of fluoropyrimidine/bevacizumab/irinotecan (intensive treatment arm; Arm B). In the present post hoc analysis, survival was evaluated with respect to the assorted mGPS categories 0, 1 or 2. Interaction between mGPS and gender was analyzed. RESULTS: Out of 421 mCRC patients treated in XELAVIRI, 362 [119 women (32.9%) and 243 men (67.1%)] were assessable. For the entire study population a significant association between mGPS and overall survival (OS) was observed [mGPS = 0: median 28.9 months, 95% confidence interval (CI) 25.9-33.6 months; mGPS = 1: median 21.4 months, 95% CI 17.6-26.1 months; mGPS = 2: median 16.8 months, 95% CI 14.3-21.2 months; P < 0.00001]. Similar results were found when comparing progression-free survival between groups. The effect of mGPS on survival did not depend on the applied treatment regimen (P = 0.21). In female patients, a trend towards longer OS was observed in Arm A versus Arm B, with this effect being clearly more pronounced in the mGPS cohort 0 (41.6 versus 25.5 months; P = 0.056). By contrast, median OS was longer in male patients with an mGPS of 1-2 treated in Arm B versus Arm A (20.8 versus 17.4 months; P = 0.022). CONCLUSION: We demonstrate the role of mGPS as an independent predictor of OS regardless of the treatment regimen in mCRC patients receiving first-line treatment. mGPS may help identify gender-specific subgroups that benefit more or less from upfront intensive therapy.

Lymphocyte subpopulations during cytomegalovirus disease in renal transplant recipients

We have determined the number of circulating T, B and natural killer cells in renal transplant recipients in order to detect changes during cytomegalovirus (CMV) infections. Serial blood samples were taken from 61 patients on standard triple immunosuppression therapy (cyclosporin A, azathioprine and prednisone). Using two-color flow cytometry analysis, the absolute number of CD3+, CD4+, CD8+, CD19+, CD3+HLA-DR+ and CD16+56+ cells was determined. Forty-eight patients (78.7 percent) developed active CMV infection, and all of them subsequently recovered. Twenty of the infected patients (32.8 percent) presented symptoms compatible with CMV disease during the infectious process. The number of lymphocytes and their main subpopulations were normal before the onset of CMV disease. During the disease there was a decrease followed by a significant increase (P<0.005) in the number of CD3+, CD4+, CD8+ and CD3+HLA-DR+ cells. No significant changes were observed in natural killer cells or B lymphocytes during the disease. We conclude, as observed in all viremic patients recovering from infection, that recovery is associated with an increase in the number of T cell subsets. The monitoring of different lymphocyte subsets along with antigenemia can be extremely useful in the detection of patients at high risk of developing CMV symptoms, allowing the early introduction of antiviral therapy or the reduction of immunosuppression therapy

Tuberculosis infantil en Valdivia: Experiencia clínica en 16 años / Tuberculosis in infancy: sixteen year experience

A clinical experience of tuberculosis (TB) in 104 pediatric patients observed at the Hospital Regional de Valdivia (southern Chile), along a sixteen year period (1986 - 2001) is presented. Pulmonary TB was diagnosed in 88 cases, extrapulmonary TB in 19 cases and both localizations in three cases. Pulmonary TB was bacteriologically confirmed in 62.5% of cases, through either gastric aspirate or sputum samples. Gastric aspirate yielded 42.8% of positive cultures; two infants who presented central nervous system involvement, died. A case of congenital TB was observed in a 30 day old infant. There were no cases of AIDS in this experience. Pediatric TB has progressively decreased its incidence in our region, particularly the extrapulmonary localization, but still represents a challenging disease to clinicians.

Rejeiçäo humoral com prova cruzada negativa: análise de 31 casos / Humoral rejection with negative crossmatch: analysis of 31 cases

Analisamos os dados clínicos, anatomopatológicos e imunológicos de 31 casos de rejeiçäo humoral (RH) com prova cruzada (PC) negativa e perda do enxerto, observados nos últimos 487 transplantes renais. Diferenciamos três tipos de rejeiçäo humoral: imediata - RHI - (1,84%), tardia - RHT (2,25%) e vascular aguda - RVA - (2,25%). Em relaçäo ao tipo de doador, a RH ocorreu em 3,96% dos casos com doador vivo parente, 7,9% com doador cadáver e em 10,4% com doador vivo näo partente e foi mais freqüente no retransplante. A prova cruzada pré-transplante foi negativa contra linfócitos T em todos os casos. Em 12 casos, foi feita utilizando-se antiglobulina humana (AGH) e manteve-se negativa. Em 11 casos, os soros foram testados contra monócitos do doador, com resultados também negativos. Apenas três casos em 12 tiveram PC positiva contra linfócitos B do doador. Doze casos de RHI e RHT tiveram as provas cruzadas repetidas pós-perda do enxerto. Um caso apresentou resultados positivos para células T, B e monócitos e outro só para monócitos. Nos seis casos de RVA que tiveram a PC repetida no pós-transplante, três apresentaram positividade para T, B e monócito e os três restantes apenas para B. Esses resultados sugerem que, apesar do PCs altamente sofisticadas, continuamos impossibilitados de prever todas as perdas por RH. Além disso, cremos que os alvos estudados parecem näo apresentar diversidade suficiente, sugerindo a participaçäo de antígenos ainda näo pesquisados na rotina pré-transplante

Aseguramiento diagnostico de la funcion renal con los metodos indirectos de aclaramiento. Informe preliminar. / Diagnostic assertiveness of renal function with indirect ethods of clearence: preliminary report

Se estudiaron tecnicas indirectas (sin sondaje vesical) de determinacion de aclaramiento, tanto en estado estacionario como en slope. Se evaluaron estas tecnicas en cuanto a su validez diagnostico. Se obtuvieron como resultados valores comparables a los obtenidos con los metodos tradicionales (con sondaje vesical), por lo cual se recomiendan funcion renal indirectas en sustitucion de las clasicas, en especial para el control de la funcion renal en pacientes de nefrologia. Se consideran los metodos clasicos, insustituibles cuando se deseen obtener valores de aclaramientos exactos y precisos

Aseguramiento diagnostico de la funcion renal con los metodos indirectos de aclaramiento. Informe preliminar. / Diagnostic assertiveness of renal function with indirect methods of clearence: preliminary report

Se estudiaron tecnicas indirectas (sin sondaje vesical) de determinacion de aclaramiento, tanto en estado estacionario como en slope. Se evaluaron estas tecnicas en cuanto a su validez diagnostico. Se obtuvieron como resultados valores comparables a los obtenidos con los metodos tradicionales (con sondaje vesical), por lo cual se recomiendan funcion renal indirectas en sustitucion de las clasicas, en especial para el control de la funcion renal en pacientes de nefrologia. Se consideran los metodos clasicos, insustituibles cuando se deseen obtener valores de aclaramientos exactos y precisos

Angioedema hereditario: revisao,apresentacao de uma familia com 15 individuos afetados e correlacao com sistema HLA. / Hereditary angioedema: review, report of a family with 15 affected subjects and correlation with the HLA system

Os autores apresentam sua experiencia com o angiodema hereditario, descrevendo diversos casos no Rio Grande do Sul. As familias acometidas foram investigadas com dosagem de C4, tipagem HLA, grupo sanguineo e Rh. Conclui-se que nao existe relacao entre o surgimento da doenca e antigenos de histocompatibilidade, grupos sanguineos ABO e Rh. A dosagem de C4 e importante na confirmacao do diagnostico clinico

HLA: principios basicos e aplicacoes clinicas em reumatologia. / HL-A: basic principles and clinical uses in rheumatology

O presente trabalho tem por objetivo proporcionar ao medico generalista uma visao basica do sistema de histocompatibilidade humana e sua aplicacao clinica. Os autores relatam alguns principios imunogeneticos e a utilidade da tipagem do sistema HLA no diagnostico de diversas artropatias, citando tres casos de sua experiencia pessoal como ilustracao

Valor da imunofluorescencia em biopsia de pele normal no diagnostico do lupus eritematoso sistemico. / Value of inmunofluorescence in normal skin biopsy in the diagnosis of systemic lupus erythematosus

Foram estudadas por meio de imunofluorescencia direta trinta e nove biopsias de pele normal de pacientes portadores de colagenoses. Procuramos observar, em nosso meio a correlacao entre depositos de imunoglobulinas e/ou complemento na juncao dermo-epidermica e o diagnostico de Lupus Eritematoso Sistemico. Foi possivel verificar a alta especificidade e sensibilidade do metodo no diagnostico diferencial dessa colagenose. Concluem os autores ressaltando o importante auxilio no diagnostico que esse procedimento pode proporcionar