Expression of Fas, FasL, and soluble Fas mRNA in endomyocardial biopsies of human cardiac allografts.

Apoptosis mediated by the Fas/Fas ligand (FasL) has been implicated in rejection of solid organ allografts and it has been recently proposed that soluble forms of Fas could interfere with this interaction, blocking apoptosis. The purpose of this study was to analyze intragraft Fas, FasL, and soluble Fas mRNA levels in relation to acute rejection in cardiac allografts in humans. mRNA levels were determined by quantitative reverse transcriptase-polymerase chain reaction in 42 samples of endomyocardial biopsies obtained from 18 cardiac transplant recipients within the first 6 months after transplantation. FasL and Fas mRNA levels were higher in biopsies with rejection than in biopsies without rejection, and no difference was observed in soluble Fas mRNA. During rejection, there was a positive correlation between the mRNA levels of Fas-FasL, Fas-soluble Fas, and FasL-soluble Fas. During quiescent periods, however, the only correlation observed was between Fas and soluble Fas mRNA levels. In conclusion, our findings do not suggest a role for soluble Fas, confirm the heightened expression of FasL, and indicate, for the first time, an increased expression of Fas in acute rejection of cardiac allografts.

Transcranial Doppler assessment of cerebral blood flow: effect of cardiac transplantation.

The authors prospectively studied transcranial Doppler changes in patients with refractory congestive heart failure before and after cardiac transplantation. They evaluated 22 patients preoperatively and 14 patients after transplantation. Mean postoperative flow velocity increased by 53.3% (p < 0.0001). Preoperative waveform changes became normal after transplantation.

Interleukin-2 gene polymorphism is associated with renal but not cardiac transplant outcome.

It was recently shown that IL-2 gene single nucleotide polymorphism (SNP) at position -330 (G-->T) is related to in vitro cytokine production levels, with the T/T and T/G genotypes being associated with low production and the G/G genotype associated with high production. The objective of this study was to investigate a possible influence of this polymorphism on renal and cardiac allograft outcomes. IL-2 SNP G-T (-330) was determined by PCR-RFLP in 67 recipients of heart allografts and in 63 recipients of renal grafts from HLA-haplo-identical, related donors. A higher frequency of the T/T genotype was observed in renal transplant patients who experienced at least one acute rejection episode during the first 3 months after transplantation than in those without rejection during this period (80% vs 49%, respectively, P <.05). Accordingly, the same genotype tended to be more frequent in renal recipients with a 6-month serum creatinine level above 1.5 mg/dL (median value for the whole group of kidney recipients) than in patients with lower creatinine levels (79% vs 45%, P <.08). Regarding cardiac transplant recipients, no associations were observed concerning acute rejection or graft survival. The finding of the association of T/T but not T/G genotype with acute kidney rejection was unexpected considering that both genotypes were shown to be associated with equal (low) IL-2 in vitro production. Further studies are necessary not only to dissect the nature of IL-2 T/T genotype association with kidney rejection, but also to explain why this genotype does not apparently influence cardiac allograft outcome.

Expression of CD40 ligand, interferon-gamma and Fas ligand genes in endomyocardial biopsies of human cardiac allografts: correlation with acute rejection

The purpose of the present study was to investigate the expression (mRNA) of CD40 ligand (CD40L), interferon-gamma (IFN-gamma) and Fas ligand (FasL) genes in human cardiac allografts in relation to the occurrence of acute cardiac allograft rejection as well as its possible value in predicting acute rejection. The mRNA levels were determined by a semiquantitative reverse transcriptase-polymerase chain reaction method in 39 samples of endomyocardial biopsies obtained from 10 adult cardiac transplant recipients within the first six months after transplantation. Biopsies with ongoing acute rejection showed significantly higher CD40L, IFN-gamma and FasL mRNA expression than biopsies without rejection. The median values of mRNA expression in biopsies with and without rejection were 0.116 and zero for CD40L (P<0.003), 0.080 and zero for IFN-gamma (P<0.0009), and 0.156 and zero for FasL (P<0.002), respectively. In addition, the levels of IFN-gamma mRNA were significantly increased 7 to 15 days before the appearance of histological evidence of rejection (median of 0.086 in pre-rejection biopsies), i.e., they presented a predictive value. This study provides further evidence of heightened expression of immune activation genes during rejection and shows that some of these markers may present predictive value for the occurrence of acute rejection.

Dissecçöes aórticas agudas: abordagem clínica e cirúrgica / Acute aortic dissections: clinical and surgical approach

As dissecçöes agudas da aorta representam uma entidade clínica não rara e de extrema gravidade. O diagnóstico precoce pode ser realizado e, para tanto, é necessário alto grau de suspeita clínica, que irá direcionar os exames a serem realizados com presteza, levando sempre em consideração a experiência da instituição com diversos exames complementares. Recomenda-se a utilização do método diagnóstico de maior acurácia e que proporcione menor estresse ao paciente. Assim que for levantada suspeita clínica de dissecção da aorta, deve ser instituída terapêutica clínica. Com a confirmação diagnóstica de diassecção envolvendo a aorta ascendente, é mandatório o tratamento cirúrgico imediato. Nos casos de dissecção da aorta descendente, o tratamento clínico é o de escolha, a menos que haja indícios de complicaçöes decorrentes da dissecção, Recentemente, novas perspectivas terapêuticas têm sido desenvolvidas e testadas com resultados bastante promissores, entre as quais destacam-se a técnica cirúrgica a tromba de elefante e o tratamento com prótese endovascular ("stent"), pela via percutânea, para correçäo das dissecçöes da aorta descendente.