Francisco Caballero

Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH

BACKGROUND/AIMS Non-alcoholic fatty liver disease (NAFLD) pathogenesis remains unknown. Due to the emerging role of free cholesterol (FC) in NAFLD, our aim was to examine the correlation between FC accumulation in patients with NAFLD and the expression of enzymes that regulate cholesterol homeostasis. METHODS Filipin staining, indicative of FC accumulation, and real-time PCR analyses were performed in 31 NAFLD patients and in seven controls. RESULTS All NASH patients (n=14) and 4 out of 17 patients with steatosis exhibited filipin staining compared to controls (0 out of 7 subjects with normal liver histology and BMI). Sterol regulatory element-binding protein-2 (SREBP-2) mRNA levels were 7- and 3-fold higher in NASH and steatosis patients, respectively, compared to controls. Since hydroxymethylglutaryl-CoA (HMG-CoA) reductase is the key enzyme in cholesterol synthesis and transcriptionally controlled by SREBP-2 we measured its mRNA levels, being 3- to 4-fold higher in NAFLD compared to controls, without any difference between NASH and steatosis patients. Fatty acid synthase (FAS) and SREBP-1c expression were not significantly induced in NAFLD, while ATP-binding cassette sub-family G member 1 (ABCG1), a transporter involved in cholesterol egress, and acyl-CoA-cholesterol acyltransferase mRNA levels were modestly increased (1.5- to 2.5-fold, p<0.05), regardless of fibrosis. Interestingly, mRNA levels of steroidogenic acute regulatory protein (StAR), a mitochondrial-cholesterol transporting polypeptide, increased 7- and 15-fold in steatosis and NASH patients, respectively, compared to controls. CONCLUSIONS FC increases in NASH and correlates with SREBP-2 induction. Moreover, StAR overexpression in NASH suggests that mitochondrial FC may be a player in disease progression and a novel target for intervention.

Extended criteria for organ acceptance. Strategies for achieving organ safety and for increasing organ pool.

Abstract: The terms extended donor or expanded donor mean changes in donor acceptability criteria. In almost all cases, the negative connotations of these terms cannot be justified. Factors considered to affect donor or organ acceptability have changed with time, after showing that they did not negatively affect graft or patient survival per se or when the adequate measures had been adopted.

Successful transplantation of organs retrieved from donors with bacterial meningitis

BACKGROUND The shortage of organs for transplantation is the most important factor limiting the number of transplants performed. Consequently, in recent years, criteria for considering a patient as a potential organ donor have been broadened. METHODS From 1995 through 1996, we have retrieved organs from five donors who were brain dead because of bacterial meningitis. The causative microorganisms were Neisseria meningitidis in one patient, Streptococcus pneumoniae in three patients, and Escherichia coli in one patient. Fifteen organs were retrieved and transplanted into 16 recipients. All the donors and recipients received adequate antibiotic therapy. RESULTS None of the recipients developed infectious complications caused by the meningeal pathogens. After a follow-up ranging from 4 to 30 months, 12 patients are alive with functioning grafts. The cause of death was noninfectious in the four patients who died. CONCLUSIONS Our study demonstrates that patients with brain death caused by bacterial meningitis due to meningococci, pneumococci, or E coli may be suitable organ donors. Transplantation of organs from such donors does not increase the risk of infection transmission to the recipient, provided that both donor and recipient had received adequate antibiotic therapy.

Increasing Human-Organ Transplant Availability: Argumentation-Based Agent Deliberation

Human-organ transplantation is the only effective therapy for many life-threatening diseases. However, despite an increase in transplant successes, the lack of a concomitant increase in donor organ availability has led to a growing disparity between supply and demand. Much research has thus focused on defining and implementing policies for increasing donor availability, identifying suitable organ recipients, and documenting transplant procedures. A novel organ-selection process uses a multiagent system called Carrel+ to let geographically dispersed transplant physicians deliberate over organ viability to increase the availability of organs for transplantation

Ecstasy-induced brain death and acute hepatocellular failure: multiorgan donor and liver transplantation.

Background. Ecstasy is a neurotoxic and hepatotoxic drug. Brain edema and fulminant hepatic failure are two of the most serious complications associated with the consumption of ecstasy. Acute ecstasy intoxication can transform a patient into an organ donor or a hepatic graft recipient. Materials and Methods. In the last 5 years in our centers, we have had two multiorgan donors who died from ecstasy-induced brain edema and three patients who required urgent orthotopic liver transplantation for treatment of severe acute hepatocellular failure induced by this drug. We performed eight transplantations using the organs of these two brain-dead donors: one heart, one bipulmonary, three kidneys, one kidney-pancreas, and two livers. Results. Toxicity caused by ecstasy was not observed in any of the eight patients who underwent transplantation. The clinical state and the graft function of the heart, two liver, renopancreatic, and three kidney recipients were normal for a follow-up period that ranged between 7 months and 4.5 years. The lung recipient died from multiorgan failure secondary to bilateral pneumonia 5 days after the transplantation, and one of the kidney transplant patients died as a result of intestinal lymphoma 6 months after transplantation. The three liver transplantations in the three patients with ecstasy-induced fulminant hepatic failure were performed successfully using orthotopic transplantation. These three recipients are asymptomatic and have normal-functioning hepatic grafts after follow-up of 3.5 years, 15 months, and 11 months, respectively. Conclusions. The thoracic and abdominal organs of people dying from ecstasy intoxication can be viable for transplantation. The short- and medium-term survival of the graft and of the recipient have been similar to that of other organ donors. Urgent liver transplantation is an effective therapeutic option in patients with ecstasy-induced acute hepatocellular failure.

Successful liver and kidney transplantation from cadaveric donors with left-sided bacterial endocarditis.

Bacterial infections are frequent in cadaveric organ donors and can be transmitted to the transplantation recipient, which could have devastating consequences for the recipients if adequate preventive measures are not adopted.

Short‐ and long‐term success of organs transplanted from acute methanol poisoned donors

Background: The shortage of organs for transplantation has made it necessary to extend the criteria for the selection of donors, among others including those patients who die because of toxic substances such as methanol. Methanol is a toxic which is distributed through all the systems and viscera of the organism and tends to cause a severe metabolic acidosis. It can specifically cause serious or irreversible lesions of the central nervous system (CNS) and retina, and ultimately brain death. We present our experience with 16 organ donors who died as a result of acute methanol intoxication in 10 Spanish hospitals over the last 14 yr. Patients and methods: Between October 1985 and July 1999, 16 organ donors with brain death caused by acute methanol intoxication, 13 females and three males with a mean age of 38.4 ± 7.6 yr (interval: 26–55 yr), allowed 37 elective transplants to be performed: 29 kidneys, four hearts and four livers for 37 recipients, and one urgent liver transplantation to a recipient with fulminant hepatitis.

Decerebrate-like posturing with mechanical ventilation in brain death

Article abstract Complex spinal cord, spontaneous, or upper limb reflexes are rarely observed in brain death. The authors describe two brain-dead heart-beating cadavers (out of 400 consecutive cases in their hospital in the past 9 years) that, immediately after brain-death diagnosis, exhibited symmetric upper limb movements resembling decerebrate posture that were triggered by each mechanical pulmonary insufflation, and also by superficial pressure and noxious stimuli applied to the arms, thorax, or abdomen. These movements persisted until disconnection from mechanical ventilation.

Elderly donor kidney grafts into young recipients: Results at 5 years

Background. To date, few data are available on older donor renal grafts transplanted into young recipients. We compare 63 kidneys grafts from donors older than 60 years transplanted into recipients younger than 60 years (group 1) with a control group of 235 patients in whom both recipients and donors were younger than 60 years (group 2). Results. Patient survival rates at 1 and 5 years, respectively, were 98% and 95% (group 1) and 95% and 84% (group 2) (P =0.01). Graft survival rates were 95% and 83% in group 1 versus 94% and 81% in group 2, although death censoring was significant (100% and 98% group 1 vs. 96% and 86% group 2, P =0.04). In group 1, plasmatic creatinemia was significantly higher. The aged donor, female donor-male recipient combination, and the presence of acute rejection alone or together with acute tubular necrosis, were determinants for worse renal functioning at 1 year after transplantation. Seven patients had chronic nephropathy not related to any clinical parameter. Conclusion. We conclude that kidneys from older donors can be successfully transplanted to younger patients.

Amniotic membrane transplantation for ocular surface pathology: long-term results.

Amniotic membrane transplantation has been used for >90 years for cutaneous and mucous lesions for regeneration of tissues. In recent years its effectiveness has been demonstrated in the treatment of diseases of the ocular surface. We present our experience with 53 amniotic membrane transplantations for different ocular pathologies with two different forms of implantation. The 53 cases were divided into three groups according to pathology and type of implant. Group 1 included 24 eyes with amniotic membrane grafts after resection of extensive conjunctival lesions. Group 2 included 19 eyes with amniotic membrane grafts for corneal pathology, and group 3 consisted of 10 eyes with amniotic membrane patches for corneal epithelial defects without ulceration. No intra- or postoperative complications were observed during an average follow-up period of 32 months (24-48 months). Group 1 demonstrated rapid healing of the lesions with minimal scarring in all cases. In group 2 a favorable response was observed in 16 of 19 cases. In group 3 complete healing was achieved in only 3 of 10 cases, and the time for which the graft remained was related to the success of the treatment. The primary intention was to achieve prolonged fixation of the implant. Finally, amniotic membrane transplantation is a safe and effective technique for the treatment of different pathologies of the ocular surface. After the resection of extensive conjunctival lesions it is currently the preferred treatment. In corneal pathology, it represents an additional therapeutic alternative when conservative medical treatments fail.