P. Ramírez

Life-supporting human complement regulator decay accelerating factor transgenic pig liver xenograft maintains the metabolic function and coagulation in the nonhuman primate for up to 8 days

Background. It is not known whether the pig liver is capable of functioning efficiently when transplanted into a primate, neither is there experience in transplanting a liver from a transgenic pigs expressing the human complement regulator human complement regulator decay accelerating factor (h-DAF) into a baboon. The objective of this study was to determine whether the porcine liver would support the metabolic functions of non-human primates and to establish the effect of hDAF expression in the prevention of hyperacute rejection of porcine livers transplanted into primates. Methods. Five orthotopic liver xenotransplants from pig to baboon were carried out: three from unmodified pigs and two using livers from h-DAF transgenic pigs. Findings. The three control animals transplanted with livers from unmodified pigs survived for less than 12 hr. Baboons transplanted with livers from h-DAF transgenic pigs survived for 4 and 8 days. Hyperacute rejection was not detected in the baboons transplanted with hDAF transgenic pig livers; however, it was demonstrated in the three transplants from unmodified pigs. Baboons transplanted with livers from h-DAF transgenic pigs were extubated at postoperative day 1 and were awake and able to eat and drink. In the recipients of hDAF transgenic pig livers the clotting parameters reached nearly normal levels at day 2 after transplantation and remained normal up to the end of the experiments. In these hDAF liver recipients, porcine fibrinogen was first detected in the baboon plasma 2 hr postreperfusion, and was present up to the end of the experiments. One animal was euthanized at day 8 after development of sepsis and coagulopathy, the other animal arrested at day 4, after an episode of vomiting and aspiration. The postmortem examination of the hDAF transgenic liver xenografts did not demonstrate rejection. Interpretation. The livers from h-DAF transgenic pigs did not undergo hyperacute rejection after orthotopic xenotransplantation in baboons. When HAR is abrogated, the porcine liver maintains sufficient coagulation and protein levels in the baboon up to 8 days after OLT.

Are personnel in transplant hospitals in favor of cadaveric organ donation? Multivariate attitudinal study in a hospital with a solid organ transplant program

Abstract:  Introduction:  A considerable number of professionals who work in a hospital could be against organ donation, which means that when the time comes, they could act as an obstacle to donation. The objective of this study was to analyze the attitude of hospital professionals toward organ donation and to determine the factors that influence this attitude in a Spanish center with a transplant program.

Attitude of hospital personnel faced with living liver donation in a Spanish center with a living donor liver transplant program

In Spain, despite its high rate of cadaveric donation, death while on the liver transplant waiting list is high. For this reason, living liver donation is being encouraged despite of the risk of morbidity for the donor. The objective of this study was to analyze attitudes toward living liver donation among hospital personnel in a hospital with a recently authorized living donor liver transplantation program. A random sample was taken and was stratified by type of service and job category (n = 1,262). Attitude was evaluated by means of a validated psychosocial questionnaire. The questionnaire was completed anonymously and was self‐administered. Statistical analysis included the Student t test, the χ2 test, and logistical regression analysis. The questionnaire completion rate was 93% (n = 1,168). Only 15% (n = 170) of respondents were in favor of living liver donation if it were unrelated. An additional 65% (n = 766) were in favor if this donation, but only for relatives. Of the rest, 9% (n = 107) did not agree with living liver donation, and the remaining 11% (n = 125) were undecided. The variables related to this attitude were age (P = 0.044); job category (P = 0.002); type of service (according to whether it is related to organ donation and transplantation) (P = 0.044); participation in prosocial activities (P = 0.026); attitude toward cadaveric organ donation (P <0.001); attitude of a respondents partner toward organ donation (P = 0.010); a respondents belief that in the future, he or she may need a transplant (P < 0.001); and a willingness to receive a donated living liver organ if one were needed (P < 0.001). There is also a close relationship between attitude toward living kidney donation and living liver donation (P < 0.001). In the multivariate analysis, the only common independent variable from the bivariate analysis was a willingness to receive a living donor liver transplant if one were needed (odds ratio = 9.3). Attitude toward living liver donation among hospital personnel in a hospital with a solid organ transplant program is favorable and is affected by factors related to cadaveric donation, altruistic activity, and feelings of reciprocity. Physicians and the youngest hospital workers are those who are most in favor, which leads us to think that there is a promising future for living liver transplantation, which is essential given the cadaveric organ deficit and the high mortality rate while on the waiting list. Liver Transpl 13:1049–1056, 2007.

German citizens in southeastern Spain: a study of attitude toward organ donation.

Ríos A, Martínez‐Alarcón L, Sánchez J, Jarvis N, Parrilla P, Ramírez P. German citizens in southeastern Spain: a study of attitude toward organ donation.
Clin Transplant 2010: 24: 349–357.

Primary health care personnel faced with cadaveric organ donation: a multicenter study in south-eastern Spain

Abstract:  Introduction:  Primary health care (PHC) is the first point of contact between the public and the health system and it is an important channel for the communication and promotion of organ donation and transplantation. The objective of this study was to analyze the attitude of PHC personnel toward donation and to determine the psychosocial variables affecting this attitude.

Inhibition of poly(ADP-ribose) polymerase attenuates the severity of acute pancreatitis and associated lung injury

The severity of acute pancreatitis results from the transmigration and activation of leukocytes within the pancreas and the local synthesis and release of proinflammatory-soluble mediators that transform a local injury into a systemic inflammatory response. Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear DNA-binding protein that has been shown to play a relevant role in cell necrosis and organ failure in various diseases associated with inflammation. Therefore, we set out to investigate whether the genetic deletion of PARP-1 or PARP-2 (a new member of the PARP family) genes, or pharmacological inhibition of PARP activity might affect the development and severity of acute pancreatitis and pancreatitis-associated lung injury. Secretagogue-induced acute pancreatitis was achieved by 12 hourly intraperitoneal injections of cerulein in mice deficient in PARP-1 or PARP-2 genes, and wild-type (WT) littermate mice untreated or treated with PARP activity inhibitors. The severity of pancreatitis was assessed by measurements of serum amylase, lipase, interleukin-1β and IL-6, pancreatic water content, histologic grading and pancreas myeloperoxidase (MPO) activity. Lung injury was evaluated by quantifying MPO activity and morphological changes. We found that the severity of acute pancreatitis and pancreatitis-associated lung injury was significantly attenuated in mice lacking PARP-1, but not PARP-2, compared with WT mice. Interestingly, administration of PARP inhibitors, 3-aminobenzamide or PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethyacetamide HCl), in WT mice markedly decreased acute pancreatitis severity and pulmonary-associated injury in a larger extension than genetic deletion of PARP-1. Our results support the potential therapeutic application of PARP inhibitors in the development and severity of acute pancreatitis and associated lung injury.

Does the standard vs piggyback surgical technique affect the development of early acute renal failure after orthotopic liver transplantation

The objective of this study was to evaluate the effect of the surgical technique on postoperative renal function during the first week after liver transplantation (OLT). We performed a retrospective study of 184 consecutive OLT. Criteria for acute renal failure were: serum creatinine >1.5 mg/dL, an increase by 50% in the baseline serum creatinine, or oliguria requiring renal replacement therapy. The distribution of patients according to the surgical technique was: standard (n=84), venovenous bypass (n=20), and piggyback (n=80). Other variables analyzed were: intraoperative requirement for blood products, treatment with adrenergic agonists, intraoperative complications, and postreperfusion syndrome. Univariate analysis showed the following parameters to be significantly related to postoperative renal failure: intraoperative fresh frozen plasma and cryoprecipitate requirements, intraoperative complications, postreperfusion syndrome, need for noradrenaline or dobutamine, standard surgical technique versus piggyback (39% vs 18%, P<.01) and venovenous vs piggyback (50% vs 18%, P<.01). Logistic regression analysis identified the following variables as having independent prognostic value: (1) Standard surgical technique vs piggyback (OR=3.3, P=.01); (2) venovenous vs piggyback (OR=4.7, P=.02); and (3) >20 U cryoprecipitate requirement (OR=1.04, P=.01). In conclusion, compared with the piggyback technique, the standard surgical technique appears to be an independent risk factor for postoperative acute renal failure. When venovenous bypass is used in patients who do not tolerate trial clamping of inferior vena cava, it does not reduce the incidence of postoperative renal failure. Finally, the piggyback technique significantly reduces the probability of acute renal failure after liver transplantation.

Isolation and characterization of immortalized porcine aortic endothelial cell lines

Primary porcine endothelial cells have a limited life span in culture. After four to five passages, they tend to de-differentiate and eventually reach senescence. The aim of this work was to establish immortalized porcine aortic endothelial cell lines (AOCs) to facilitate in vitro studies of different pathological process involving the endothelium. Primary porcine aortic endothelial cells (PAECs) were transfected with a plasmid containing the SV40 genome and selected on the basis of morphological and phenotypical features. Flow cytometry analysis demonstrated uptake of acetylated low density lipoproteins (Ac-LDL) and constitutive expression of SLA class I, CD29, CD31, CD41/61, CD80/86, CD46, SWC3, and LAMP-1 antigens by all analyzed lines and showed little differences to primary cells. The functional similarity between primary and immortalized endothelial cells was demonstrated in a cytotoxicity assay using a human natural killer cell line (NKL) as effector. The AOCs cell lines should be valuable tools for in vitro study of the human immune response against pig endothelial cells. In addition, they would be very useful to gain insight in the pathogenesis of some viral haemorrhagic diseases of pig such as African swine fever (ASF) or classical swine fever (CSF).

The Latin American population in Spain and organ donation. Attitude toward deceased organ donation and organ donation rates

The Latin American (LA) population has similarities with the Spanish population which makes its integration into Spanish society easier. Objective: to analyze the attitude toward organ donation among Latin American citizens residing in Spain, to determine the psychosocial variables which affect this attitude, and to examine the correlation between donation rates of LA citizens in Spain and in their countries of origin. A random sample of LA residents in Spain was taken and stratified according to the respondents nationality (n = 1.314), in the year 2010. Attitude was assessed using a validated questionnaire (PCID‐DTO Dr Rios). The survey was self‐administered and completed anonymously. Statistical analysis: Students t‐test, the χ2 test, and logistic regression analysis. There was a 94% completion rate (n = 1.237). Attitude toward donation was favorable in 60% of cases (n = 745), 12% (n = 145) were against, and 28% (n = 347) were undecided. The following variables were associated with attitude toward donation: sex (P = 0.038), level of formal education (P < 0.001), country of origin (P = 0.002), attitude toward the donation of a family members organs (P < 0.001), having discussed donation with the family (P < 0.001), carrying out prosocial activities (P = 0.025), attitude toward cremation of the body (P < 0.001), attitude toward burial of the body (P < 0.001), attitude toward having an autopsy carried out (P < 0.001), previous experience of the organ donation and transplantation process (P < 0.001), fear of mutilation after donation (P < 0.001), knowledge that the Church has a positive attitude toward organ donation and transplantation (P < 0.001), knowledge of ones partners attitude toward organ donation (P < 0.001), and a belief that one might need a transplant in the future (P < 0.001). The donation rates in this population group in Spain are higher than those recorded in their countries of origin (55.76 vs. <10 pmp; P < 0.001). The attitude toward organ donation among LA citizens residing in Spain is slightly worse than that reported in the native Spanish population and is determined by many psychosocial factors. The donation rates of LA citizens in Spain are higher than those in their countries of origin.

Can we expand the indications for liver transplantation among hepatocellular carcinoma patients with increased tumor size

INTRODUCTION Due to the scarcity of donors and the fact that size is the main prognostic factor, Milan criteria have been used since 1996 to select hepatocellular carcinoma (HCC) patients for liver transplantation. In 2001 UCSF criteria showed that including layer tumors did not reduce the survival results. The objective of this paper was to evaluate whether HCC tumor sizes exceeding the Milan criteria adversely influence survival rates. PATIENTS AND METHODS Between May 1988 and July 2001, 53 patients were transplanted due to HCC and cirrhosis. The etiology of cirrhosis was HCV in 23 cases and HBV in 6. In 11 cases the HCC were incidental by discovered namely, a mean/ diameter of 1.8 cm (versus 2.6 cm in nonincidental HCC). Sixty-two percent of tumors met the Milan criteria, and 68% the USCF criteria. RESULTS The actuarial survival was 79% at 1 year and 62% at 5 years. The survival of patients with incidental HCC was 82% at 1 year and 82% at 5 years, which is better than the survival of those with nonincidental HCC (78% at 1 year and 57% at 5 years, P<.05). According to Milan criteria, the survival patients with early tumors was 82% at 1 year and 68% at 5 years, and for advanced tumors (NS), 75% and 54%, respectively. Comparison of early versus advanced tumors according to UCSF criteria showed survivals of 84% versus 64% at 1 year (P<.05) and 67% versus 48% at 5 years (P<.05), respectively. CONCLUSION Increasing the HCC size among LT according to the California criteria did not reduce survival rates compared with the Milan criteria.