Life supporting function for over one month of a transgenic porcine heart in a baboon.

BACKGROUND: Inhibition of hyperacute rejection (HAR) and sustained graft survival have been demonstrated in a pig-to-primate model of heterotopic cardiac xenotransplantation using pigs transgenic for human Decay Accelerating Factor (hDAF). Building on this work, an orthotopic model has been developed. This case records 39-day cardiac xenograft function in a life-supporting capacity with clinically applicable immunosuppression. METHODS: Using a heart from an hDAF transgenic pig, an orthotopic cardiac transplant was performed on an adult baboon. The immunosuppressive regimen consisted of induction with a short course of cyclophosphamide, followed by maintenance therapy with cyclosporine A, mycophenolate mofetil and a tapering course of corticosteroids. Post-operative monitoring included daily anti-pig hemolytic antibody titer surveillance and endomyocardial biopsy. RESULTS: The animal survived 39 days and was active and energetic throughout its postoperative course, remaining free of signs of cardiopulmonary failure. Endomyocardial biopsy performed on post-operative Day 36 revealed only patches of sub-endocardial fibrosis with no signs of active rejection. The baboon succumbed to an acute cardiopulmonary decompensation immediately following administration of medication via oral gavage. Post-mortem histopathology demonstrated well-preserved myocardial architecture with small foci of mild humoral rejection. CONCLUSIONS: This case documents the longest survival recorded to date of a discordant orthotopic cardiac xenograft and illustrates that the hDAF transgene combined with a clinically acceptable maintenance immunosuppressive regimen enables sustained, life-supporting function of porcine cardiac xenografts in non-human primates. The inhibition of hyperacute rejection and the subsequent control of humoral and cellular rejection for over 1 month demonstrated in this experiment represent significant progress in the development of a viable strategy for clinical xenotransplantation.

Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass.

Heparin is normally used for anticoagulation during cardiopulmonary bypass (CPB), but its use is contraindicated in patients with a history of heparin-induced thrombocytopenia, heparin-provoked thrombosis, or both. Heparin therapy can also be ineffective due to heparin resistance. A short-acting, oligonucleotide-based thrombin inhibitor (thrombin aptamer) may potentially serve as a substitute for heparin in these and other clinical situations. We tested a novel thrombin aptamer in a canine CPB pilot study to determine its anticoagulant efficacy, the resultant changes in coagulation variables, and the aptamer's clearance mechanisms and pharmacokinetics. Seven dogs were studied initially: Four received varied doses of the aptamer (to establish the pharmacokinetic profile) and 3 received heparin. Subsequently, 4 other dogs underwent CPB, receiving a constant infusion of the aptamer before CPB (to characterize the baseline coagulation status), with partial CPB and hemodilution, during 60 minutes of total CPB, and, finally, after a 2-hour recovery period. At a 0.5 mg.kg-1.min-1 dose, the activated clotting time rose with aptamer infusion from 106 +/- 12 seconds to 187 +/- 8 seconds (+/- 1 standard deviation) (p = 0.014), increased further with hemodilution (to 259 +/- 41 seconds; p = 0.017), and was even more prolonged during total CPB (> 1,500 seconds; p < 0.001). This later increase in the activated clotting time paralleled a rise in the plasma concentration of the thrombin aptamer during total CPB, as determined by high-performance liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Xenotransplantation.

BACKGROUND: The success of clinical transplantation has led to a large discrepancy between donor organ availability and demand; considerable pressure exists to develop an alternative source of organs. The use of animal organs for donation is a possible solution that is not yet clinically applicable. METHODS AND RESULTS: A literature review was performed based on a Medline search to find articles on xenotransplantation. Keywords included hyperacute, acute vascular, xenograft rejection combined with concordant and discordant. Additional references cited in these articles from journals not included in Medline were obtained from the British Library. Limited information on unpublished, preliminary work has been included from sources known to the authors, based on their research work in the field. One hundred and forty-six references and four personal communications have been included in this review article. CONCLUSION: A greater understanding of the pathogenesis of xenograft rejection is developing rapidly. Strategies to abrogate hyperacute rejection have proved successful, but control of antibody-driven acute vascular rejection has not yet been achieved. The safety and viability of xenotransplantation as a therapeutic modality are still unproven.

Utilidad de la tira reactiva de orina en el diagnóstico de meningitis bacteriana aguda / Utility of urine strip in the diagnosis of acute bacterial meningitis

La meningitis bacteriana aguda (MBA) es un cuadro grave de alto porcentaje de secuelas y alta letalidad, por lo que el laboratorio clínico tiene un papel fundamental en el diagnóstico precoz. Dado que es de gran utilidad disponer de métodos sencillos se evaluó la utilidad de la tira reactiva de orina Combur 10R (para los parámetros de glucosa, proteínas y leucocitos) y del resto de los exámenes de laboratorio en muestras de LCR en la obtención de un diagnóstico rápido de MBA. Para esto se estudiaron 87 muestras de LCR que ingresaron al Laboratorio de Urgencia del Hospital Clínico de la Pontificia Universidad Católica de Chile proveniente de pacientes con sospecha clínica de MBA. A estos se les realizó estudio citoquímico, recuento celular, tinción de Gram, test de aglutinación por látex y la tira reactiva de orina Combur 10MR, evaluando visualmente los parámetros de glucosa, proteínas y leucocitos. De los 87 LCR analizados, en 13 el diagnóstico definitivo fue MBA, en 2 meningitis viral y en 72 otros. La sensibilidad y especificadad diagnóstica de la tira reactiva para dos parámetros (cualquier combinación) fueron de 100 por ciento y 87,8 por ciento respectivamente. Para tres parámetros positivos la sensibilidad fue de 76,9 por ciento, que aumentó al 84,6 por ciento si se complementa con la información de la tinción de Gram y aun 92,3 por ciento si se agrega a lo anterior el test de aglutinación por látex. Se concluye que la tira reactiva de orina Combur 10MR es un método diagnóstico suficientemente sensible, rápido y simple que puede ser utilizado como método de aproximación diagnóstica en MBA. Dado el rendimiento y alto costo del test de aglutinación por látex, se recomienda reservarlo para aquellos casos en que los otros métodos diagnóticos orienten fuertemente al diagnóstico de MBA