Moderate calorie restriction during gestation programs offspring for lower BAT thermogenic capacity driven by thyroid and sympathetic signaling.

BACKGROUND: Maternal calorie restriction during pregnancy programs offspring for later overweight and metabolic disturbances. Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis and has recently emerged as a very likely target for human obesity therapy. OBJECTIVE: Here we aimed to assess whether the detrimental effects of undernutrition during gestation could be related to impaired thermogenic capacity in BAT and to investigate the potential mechanisms involved. METHODS: Offspring of control and 20% calorie-restricted rats (days 1-12 of pregnancy) (CR) were studied at the age of 25 days. Protein levels of uncoupling protein 1 (UCP1) and tyrosine hydroxylase (TyrOH); mRNA levels of lipoprotein lipase (LPL), carnitine palmitoyltransferase 1 (CPT1) and deiodinase iodothyronine type II (DIO2) in BAT; and blood parameters including thyroid hormones, were determined. The response to 24-h cold exposure was also studied by measuring body temperature changes over time, and final BAT UCP1 levels. RESULTS: Compared with controls, CR animals displayed in BAT lower UCP1 and TyrOH protein levels and lower LPL and CPT1 mRNA levels; they also showed lower triiodothyronine (T3) plasma levels. CR males, but not females, revealed lower DIO2 mRNA levels than controls. When exposed to cold, CR rats experienced a transient decline in body temperature, but the values were reestablished after 24 h, despite having lower UCP1 levels than controls. CONCLUSIONS: These results suggest that BAT thermogenic capacity is diminished in CR animals, involving impaired BAT sympathetic innervation and thyroid hormone signaling. These alterations make animals more sensitive to cold and may contribute to long-term outcomes of gestational calorie restriction in promoting obesity and related metabolic alterations.

The living kidney donation process: the donor perspective.

OBJECTIVE: To evaluate the living kidney donation (LKD) process using donors' opinions on the impact on social, emotional, and financial aspects affecting donor quality of life. MATERIALS AND METHODS: From May 2000 to December 2002, we studied 22 donors of living kidneys at the Hospital Clinic, Barcelona, Spain, who completed an anonymous survey 6 months after donation. RESULTS: Most donors (86%) had themselves informed the recipient about their wish to donate, the other 14% were asked by family members. Eighty-eight percent stated that the information provided to the donor about the evaluation process was well explained and understood whereas 12% disagreed with the statement. At the time of thin decision, 90.5% of donors understood the vital risk. For 95%, the explanations about the process corresponded with the actual experience. One hundred percent of donors stated after donation that they would again favor it. Mean hospital stay was 6 days (range, 3-9 days). Those donors with a labor contract have been out of work for an average of 57.8 days (range, 18 days to 6 months). Twenty-five percent of donors admitted financial effects as a result of donation. All but 1 felt completely recovered with the same quality of life after donation. DISCUSSION: LKD is a good therapeutic alternative. Some aspects should be developed, such as more information about living donation and the need to considering donors as healthy persons without loss of earnings. Recognition of the benefits of living donation requires more wide participation of all citizens nationally.

Functions, responsibilities, dedication, payment, organization, and profile of the hospital transplant coordination in Spain in 2002.

In Spain, the number of donors per million of population and the activity of transplantation is a direct consequence of the continued work of the hospital transplant coordinators. There are 146 procurement hospitals with approximately 534 transplant coordinators (13.6 coordinators per hospital and 12.7 per million of population). A voluntary survey of 74 Spanish transplant coordinators revealed 67.6% to be men and 32.4% women of average age 43 years with specialization of 75.7%, Intensive Care Medicine; 8.1%, Anesthesiology; 6.7%, Nephrologists; and the rest, General Surgery or without any specialization. Among the group who responded to the injury, 86.5% were doctors and 13.5%, nurses. The overall team is composed of 52% doctors, 27.7% nurses and others with 70.3% working part-time and 27%, full-time. Previous experience was noted to be less than 5 years among 51.4%, and more in the rest of the cases. The 85% work under medical direction by management. Their payment includes salary plus activity in 48.7% of the cases; 21.6%, only salary, and 18.9%, only activity. Each coordinator generates between 3 and 7 organ as well as 3 and 11 of tissue donors. In conclusion, comparing this data with the practice in the United States demonstrates the unique aspects of the Spanish system.

Evaluation of transplant procurement management courses: an educational project as a tool for the optimization of transplant coordination.

The process of obtaining organs and tissues includes a series of procedures and skills that are fundamental to obtain a large number and high quality of transplants. Health professionals involved in transplant coordination require robest and comprehensive training to integrate the donation-transplantation process within the clinical health care field. Based on a learning-through-experience model, Transplant Procurement Management (TPM) designed various courses adapted to local educational need to train transplant coordinators, to increase active donor detection, and to promote a positive attitude towards donation; namely, Advanced, Introductory and New Life Cycle courses respectively. Moreover, TPM has coordinated international programs (INTERCATT and INTERITALY). Since 1991, the model has included 29 Advanced courses (1215 participants), 22 Introductory courses (575 pupils), and 7 New Life Cycle courses (more than 400 attendees). The Advanced courses were attended by medical (intensive care unit, nephrology, and others) and nursing professionals. Assessment of the educational program showed achievement of teaching objectives. The evaluation averages above 3.5 (scale, 1-5) for content, presentation, and ability to answer questions. Likewise, the program's organization showed an average score of 4.4. The acquired knowledge was assessed by means of a self-evaluation test (correct answers >69%). Practical skills assessed through direct observation showed an average of 7 (scale, 1-10). The TPM educational program offers a range of necessary knowledge and skills to increase organ donation. Health professionals concerned about the organ shortage may find TPM training useful to increase their knowledge.

Persistence of intracranial diastolic flow in transcranial Doppler sonography exploration of patients in brain death.

OBJECTIVE: The persistence of cerebral blood flow (CBF) in patients with whole brain death (BD) diagnosis is an unusual phenomenon. We describe patients with whole BD diagnosed despite persistence of intracranial blood flow on transcranial Doppler sonography (TDS). MATERIALS AND METHODS: From January 2001 to December 2002, we reviewed the records of 11 patients. Etiology of BD was craniocephalic trauma in 2 cases, schemic cerebrovascular accident (CVA) in 4 cases, Hemorrhagic CVA in 3 cases, subaracnoid hemorrhage in 1 case, and acute hydrocephalus in 1 case. Six patients had a cerebral decompressive mechanism. In all patients, TDS was used to confirm BD after clinical diagnosis. Additionally, all patients underwent an electroencephalogram (EEG). In 3 patients cerebral angiography (CA) and in 2 others radionuclide angiography (RA) with Tc99m HMPAO were done. RESULTS: All TDS studies showed persistent telediastolic positive flow in at least 1 artery. Because the TDS did not confirm the clinical diagnosis of BD, EEG tests were performed showing silence of bioelectrical activity. Those cases showed CA or RA results with a complete absence of CBF. CONCLUSION: The TDS technique directly evaluates the intracranial but not the intracerebral circulation. For this reason, during the BD diagnosis for patients with previous decompressive techniques, it was possible to find persistence of intracranial telediastolic flow using TDS. In those cases, it is advisable to use other tests to confirm the clinical diagnosis of BD.

The process of adult living liver donation.

OBJECTIVE: To evaluate both the opinion that living liver donors have of the process and the psychological, economic, and social consequences of donation. MATERIAL AND METHODS: Six months after the donation, an anonymous survey was sent to 22 donors of the right liver lobe between March 2000 and December 2002. RESULTS: 15 surveys were returned with all of the questions answered. Almost all the donors had no prior knowledge of living donation. When they were considered to be suitable donors, all of them felt happy, 21% were scared and 15% felt joy and insecurity. The information provided was well understood and accurately described the experiences of 93% of donors. All donors understood the vital risk, and 93% understood that transplantation is not always completely successful. All donors would repeat the experience. Mean hospital stay was 12.6 days. Mean convalescence was 50.6 days. Salaried donors were on sick leave for a mean of 96.4 days (21-150 days), causing financial problems in six cases (36%), due to no financial compensation and compulsory redundancy in one case. All donors had completely recovered at six months after donation. DISCUSSION: Adult living donation of the right liver lobe is an accepted therapeutic alternative. In order to regulate medical and economic protection to avoid additional disturbances after donation, the public, patients, and physicians require more complete information about living donation.

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. RESULTS: The immediate postoperative period was favourable for the 38 graft recipients. None of the graft recipients presented gap anion metabolic acidosis in the immediate postoperative period, nor symptomatology or lesions of the CNS characteristic of methanol intoxication. Two patients died during the first month post-transplantation, a liver recipient and a heart recipient, at 16 and 24 days, respectively, because of acute rejection of the graft. At 1 month after transplantation 35 of the 36 recipients had been discharged from hospital with normal-functioning grafts. The last of the recipients, a kidney recipient, was discharged at 6 wk with normal-functioning graft. Actuarial survival of the graft and patient of kidney recipients at 1, 3 and 5 yr was 92.6, 77.8, and 75%, and 100, 88.9 and 83.3%, respectively; with average serum creatinines of 139.9 +/- 42.9, 150.4 +/- 42.8, and 164.4 +/- 82.5 micromol/L, respectively. At 1 yr after transplantation the three heart recipients and two of the three liver recipients had normal-functioning graft. CONCLUSIONS: Methanol intoxication is not transferred from the donor to the recipient. The survival of the graft and kidney, heart and liver recipients using organs from donors who die because of methanol does not differ in the short- and long-term from the transplants performed with organs from donors who die from other causes.

Hepatic xanthine levels as viability predictor of livers procured from non-heart-beating donor pigs.

BACKGROUND: The aim of the present study was to evaluate hepatic content of adenine nucleotides and their degradation products in non-heart-beating donor (NHBD) pigs and its relationship with recipient survival. METHODS: Thirty animals were transplanted with an allograft from NHBDs. After warm ischemia (WI) time (20, 30, or 40 min), cardiopulmonary bypass and normothermic recirculation (NR) were run for 30 min. Afterward, the animals were cooled to 15 degrees C and liver procurement was performed. RESULTS: Survival rate was 100% in the 20WI, 70% in the 30WI, and 50% in the 40WI. Livers from non-surviving animals had higher levels of xanthine after NR than livers from surviving animals. Logistic regression analysis revealed that xanthine at the end of NR was the only variable able to predict survival with a calculated sensitivity of 80% and a specificity of 60%. Prolongation of warm ischemic period leaded to a greater xanthine accumulation as well as increased plasma alpha-glutathione S-transferase levels at reperfusion. Xanthine at NR and alpha-glutathione S-transferase at reperfusion significantly correlated, indicating that donor xanthine contributes to some extent to the severity of the lesion by ischemia-reperfusion. CONCLUSIONS: It is suggested that xanthine content in the donor is able to predict survival after transplantation. Xanthine is significantly involved in the hepatic lesion elicited by warm ischemia and subsequent ischemia-reperfusion associated to liver transplantation from a NHBD.

Proyecto TPM (Transplant Procurement Management): Formación avanzada internacional de coordinadores de trasplante / The TPM Project (Transplant Procurement Management): international advanced training of transplant coordination

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Normothermic recirculation reduces primary graft dysfunction of kidneys obtained from non-heart-beating donors.

Our aim was to analyze the short- and long-term function of kidneys procured from non- heartbeating donors (NHBD) by means of three techniques: in situ perfusion (ISP), total body cooling (TBC) and normothermic recirculation (NR). Fifty-seven potential NHBD were included. Mean warm ischemia time was 68.9 +/- 35.6 min. Forty-four kidneys were obtained from donors perfused with ISP, 8 with TBC, and 8 with NR. Eighteen kidneys (32%) started functioning immediately, 29 (52%) showed delayed graft function (DGF) and 9 (16%) showed primary non function (PNF). The actuarial graft survival rate was 76.4% at 1 year and 56% at 5 years. The patient survival rate was 89.3% at 5 years. Incidence of DGF and PNF was significantly lower in kidneys perfused with NR than those with ISP or TBC (P < 0.01). Duration of DGF was shorter in kidneys obtained through TBC than in kidneys obtained with ISP (P < 0.05). In conclusion, NR reduces the incidence of DGF and may be considered the method of choice for kidney procurement from NHBD.

Cardiovascular tissue banking in the non-cadaveric setting: ten-year experience of a university hospital-based bank with active organ donation program.

BACKGROUND AND AIM OF THE STUDY: Today, transplantation of cardiovascular tissues is common practice, and tissue banking has become routine. Consequently, many institutions exist which carry out high-quality tissue banking. METHODS: The Hospital Clinico of the University of Barcelona established its cardiovascular tissue bank in 1989. The bank follows international and national regulations, and functions as a non-profit-making organization. Organ and tissue donors are recruited by the Transplant Coordination unit, which works closely with the Catalonian Organ Transplant Network (OCAT) and the Spanish National Organ Transplantation Network (ONT). The hearts are removed during multi-organ donation and processed using aseptic techniques in a laminar flow hood. Hearts are only accepted from brain-dead multiorgan and non-beating-heart donors. The heart valves are dissected, decontaminated, cryopreserved in specific media and stored in liquid nitrogen at -196 degrees C under strict bacteriological and serological control. RESULTS: Between 1989 and 1999, a series of 1,005 cardiovascular donors from within Spain was identified, from which 840 hearts were processed. After evaluation, 1,099 (65.4%) valves were cryopreserved, and 1,023 (61.5%) given clearance for implantation. In total, 534 aortic, 530 pulmonary, 33 mitral and two tricuspid valves were processed; ultimately 92.8% of aortic and 93.9% of pulmonary valves were accepted for clinical implantation. The rejection rate was 39.1%. Homografts were transported to their destination in dry ice in a cryogenic container. Overall, 608 valves were implanted at our own institution and at hospitals in Barcelona and Europe. Only two cases of complaint were received from implanting surgeons. CONCLUSION: After ten years' experience, the degree of satisfaction of implanting surgeons appears to be adequate. Strict control of the entire tissue banking process has permitted the availability of high-quality homografts for clinical implantation.