Brain Death

As compared with diaphragm-biopsy specimens from controls, specimens from case subjects showed decreased cross-sectional areas of slow-twitch and fast-twitch fibers of 57% (P = 0.001) and 53% (P = 0.01), respectively, decreased glutathione concentration of 23% (P = 0.01), increased active caspase-3 expression of 100% (P = 0.05), a 200% higher ratio of atrogin-1 messenger RNA (mRNA) transcripts to MBD4 (a housekeeping gene) (P = 0.002), and a 590% higher ratio of MuRF-1 mRNA transcripts to MBD4 (P = 0.001).

Glasgow Coma Scale ICP Intracranial pressure MMCAI Malignant middle cerebral artery infarction AIM Mortality from malignant middle cerebral artery infarction (MMCAI) approaches 80% in adult series. Although decompressive craniectomy decreases mortality and leads to an acceptable outcome in selected adult patients, there are few data on MMCAI in children with stroke. This study evaluated the frequency of MMCAI and the use of decompressive craniectomy in children.

To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. Methods: The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. Results: TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial stenoocclusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

When deoxygenated, blood behaves as an effective susceptibility contrast agent. Changes in brain oxygenation can be monitored using gradient-echo echo-planar imaging. With this technique, difference images also demonstrate that blood oxygenation is increased during periods of recovery from respiratory challenge. © 1991 Academic Press, Inc.

Given the shortage of cadaveric organs, we began a study utilizing NHBD for OLTx and KTx. There were 24 NHBD between January 1989 and September 1993. These donors were divided into 2 groups: uncontrolled NHBD (G1) (n=14) were patients whose organs were recovered following a period of CPR; and controlled NHBD (G2) (n=10) were patients whose organs were procured after sustaining cardiopulmonary arrest (CA) following extubation in an operating room setting. Eight kidneys and 5 livers were discarded because of macroscopic or biopsy findings. In G1, 22/27 (81.5%) kidneys were transplanted; 14/22 (64%) developed ATN; 20/22 (95%) recipients were off dialysis at the time of discharge. With a mean follow-up of 32.7± 21.1 months, sixteen (73%) kidneys are still functioning, with a mean serum creatinine of 1.7±0.6 mg/dl. The one-year actuarial patient and graft survivals are 95% and 86%. In G2, 17/20 (85%) kidneys were transplanted; 13/17 (76%) kidneys experienced ATN. All patients were off dialysis by the time of discharge. With a mean follow-up of 17.6±15.4 months, twelve (70%) kidneys are still functioning, with a mean serum creatinine of 2.5±2.1 mg/dl. The one-year actuarial patient and graft survivals are 94% and 82%, respectively. In G1, 6/10 (60%) livers were transplanted; 3/6 (50%) livers functioned, the other 3 patients required ReOLTx in the first week postoperatively because of PNF(n=2) and inadequate portal flow (n=1). Two functioning livers were lost due to HAT (n=1) and CMV hepatitis (n=1). In G2, 6/7 (85.7%) livers were transplanted. All the livers (100%) functioned. 2 patients required ReOLTx for HAT at 0.9 and 1.0 months. Both patients eventually died. One patient with a functioning liver died 2 months post OLTx. The remaining 3 patients are alive and well at 27 months of follow-up. This study shows that the procurement of kidneys from both uncontrolled and controlled NHBD leads to acceptable graft function despite a high incidence of ATN. The function of liver allografts is adequate in the controlled NHBD but suboptimal in the uncontrolled NHBD, with a high rate of PNF.

Objective: To determine whether the outcomes of liver transplantation (LTx) from donation after cardiac death (DCD) donors are equivalent to those from donation after brain death (DBD) donors. Summary Background Data: Because of the significant donor organ shortage, more transplant centers are using livers recovered from DCD donors. However, long-term, single-center outcomes of liver transplantation from DCD donors are limited. Methods: From January 1, 1993, to July 31, 2002, 553 liver transplants were performed from DBD donors and 36 were performed from DCD donors. Differences in event rates between the groups were compared with Kaplan-Meier estimates and the log-rank test. Differences in proportion and differences of means between the groups were compared with Fisher exact test and the Wilcoxon rank sum test, respectively. Results: Mean warm ischemic time at recovery in the DCD group was 17.8 Ϯ 10.6 minutes. The overall rate of biliary strictures was greater in the DCD group at 1 year (33% versus 10%) and 3 years (37% versus 12%; P ϭ 0.0001). The incidence of hepatic artery thrombosis, portal vein stenosis/thrombosis, ischemic-type biliary stricture (ITBS), and primary nonfunction were similar between groups. However, the incidence of both hepatic artery stenosis (16.6% versus 5.4%; P ϭ 0.001) and hepatic abscess and biloma formation (16.7% versus 8.3%; P ϭ 0.04) were greater in the DCD group. Trends toward worse patient and graft survival and increased incidence of ITBS were seen in DCD donors greater than 40 years compared with DCD donors less than 40 years. Overall patient survival at 1 year (DCD, 80%; versus DBD, 91%) and 3 years (DCD, 68%; versus DBD, 84%) was significantly less in the DCD group (P ϭ 0.002). Similarly, graft survival at 1 year (DCD, 67%; versus DBD, 86%) and 3 years (DCD, 56%; versus DBD, 80%) were significantly less in the DCD group (P ϭ 0.0001).

Transplantation has evolved as the treatment of choice for many patients with end-stage organ disease. However, despite the Ͼ80% one-year functional survival rate of most transplanted organs at the present time, the ultimate goal-to provide long-term treatment for an irreversible process-has not been achieved; the rate of attrition over time has not changed appreciably throughout the entire experience (1). Although recurrent disease, de novo infections, malignancies, and other factors may contribute to late graft deterioration, chronic rejection remains the most important etiologic factor (2). Despite well-characterized functional and morphological changes, the mechanisms leading to this progressive state remain poorly understood. Its pathophysiology has been conceptualized as stemming from both antigendependent and -independent risk factors (3). Although immune-mediated events are considered to be primarily responsible for the late graft changes, it seems increasingly that the influence of nonimmunological events has been underestimated. This concept has been emphasized by recent pooled United Network of Organ Sharing data that show that the survival rates of kidneys from living-unrelated and one haplotype-matched living-related donors are identical despite potentially important differences in genetic relationship with the given recipient (4). In addition, organs from all living donors demonstrate consistently superior results to those from cadaver sources over both the short-and long-term. Various nonimmunological factors that might explain these discrepancies include the effects of initial ischemia/reperfusion injury, inadequate functioning nephron mass, viral infections, and drug toxicity.

To survey brain death criteria throughout the world. Background: The clinical diagnosis of brain death allows organ donation or withdrawal of support. Declaration of brain death follows a certain set of examinations. The code of practice throughout the world has not been systematically investigated. Methods: Brain death guidelines in adults in 80 countries were obtained through review of literature and legal standards and personal contacts with physicians. Results: Legal standards on organ transplantation were present in 55 of 80 countries (69%). Practice guidelines for brain death for adults were present in 70 of 80 countries (88%). More than one physician was required to declare brain death in half of the practice guidelines. Countries with guidelines all specifically specified exclusion of confounders, irreversible coma, absent motor response, and absent brainstem reflexes. Apnea testing, using a PCO 2 target, was recommended in 59% of the surveyed countries. Differences were also found in time of observation and required expertise of examining physicians. Additional provisions existed when brain death was due to anoxia. Confirmatory laboratory testing was mandatory in 28 of 70 practice guidelines (40%). Conclusions: There is uniform agreement on the neurologic examination with exception of the apnea test. However, this survey found other major differences in the procedures for diagnosing brain death in adults. Standardization should be considered.

During the past few years, there has been renewed interest in the use of expanded criteria donors (ECD) for kidney transplantation to increase the numbers of deceased donor kidneys available. More kidney transplants would result in shorter waiting times and limit the morbidity and mortality associated with long-term dialysis therapy.

Background. There is mounting evidence from experimental and clinical studies that the quality of organs from cadaver donors may be influenced by events occurring around the time of brain death, and that these may affect transplant outcome. The aim of this study is to investigate the influence of donor factors on renal allograft outcome in a homogeneous cohort of 518 patients transplanted in a single centre over a 9 year period. Methods. Endpoints of the study were delayed graft function (DGF), acute rejection (AR), 1 year graft survival and long-term survival of those grafts that reached 1 year. Multivariate analysis was performed to determine factors that may have influenced the graft outcome indicators. Results: DGF was the major predictor of graft failure overall with cold ischaemia time (CIT) as an important independent factor. The level of histocompatibility did not influence graft survival. DGF was the major factor affecting 1 year graft survival (P<0.0005) with effects persisting beyond 1 year. DGF was significantly influenced by CIT, donor age, female kidney into male recipient and donor creatinine (P<0.05). Other donor factors and factors associated with donor management were not risk factors for DGF, rejection episodes or graft survival. The risk factors for a number of AR episodes were HLA-DR mismatch and DGF (P<0.005). When grafts surviving for 1 year were considered, only CIT, recipient age and creatinine at 1 year (P<0.05) were found to affect graft survival significantly.

Ischemia has been an inevitable event accompanying the procedure of kidney transplantation. Ischemic changes start with brain death which is associated with severe homodynamic disturbances: increasing intracranial pressure results in bradycardia and decrease in cardiac output; Cushing reflex causes tachycardia and increase of blood pressure, and after short period of stabilization, systemic vascular resistance declines with hypotension leading to cardiac arrest. Free radical mediated injury occurs and release of pro-inflammatory cytokines and activation of the innate immunity develops. It has been is suggested that all of these changes -the early innate response and the ischemic tissue damage play a role in development of adaptive response which in turn may lead to acute kidney rejection, Hypothermic kidney storage of various duration before transplantation adds to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion. Reperfusion injury, as an effector phase of ischemic injury, develops hours or days after initial insult. Repair and regeneration process occur along with cellular apoptosis, autophagy and necrosis, and the fate of the organ depends on whether cell death or regeneration prevails. The whole process has been described as the ischemia/reperfusion injury. It has profound influence not only on the early, but also late function of the transplanted kidney. Prevention of I/R injury should be started before recovery of the organs (donor pretreatment).

To conduct a meta-analysis to enhance understanding of the risks of biliary complications, particularly ischemic cholangiopathy (IC), after donation after cardiac death (DCD) compared with donation after brain death (DBD) liver transplantation.

We report pronounced and specific antiglioblastoma cell phototoxicity of 5 nm TiO 2 particles covalently tethered to an antibody via a dihydroxybenzene bivalent linker. The linker application enables absorption of a visible part of the solar spectrum by the nanobio hybrid. The phototoxicity is mediated by reactive oxygen species (ROS) that initiate programmed death of the cancer cell. Synchrotron X-ray fluorescence microscopy (XFM) was applied for direct visualization of the nanobioconjugate distribution through a single brain cancer cell at the submicrometer scale.

The aim of this study was to compare the survival and midterm function of kidneys from non-heart beating donors (NHBD) with those of kidneys from heart beating donors (HBD). From 1989 to 1998, 144 kidneys were procured from NHBD at the Hospital Clínico San Carlos in Madrid, of which 95 were transplanted. The kidney grafts were maintained from the moment of the diagnosis of cardiac arrest until the time of procurement by cardiopulmonary bypass. There was no significant difference in renal function and the number of rejection episodes between the NHBD and HBD transplants. The NHBD kidneys showed a 5.73-fold increase in the incidence of delayed graft function (adjusted relative risk 95% confidence interval, 2.82 to 11.62). One-and five-year survival rates for NHBD grafts were 84.6 and 82.7%, respectively, compared

The majority of transplants are derived from donors who suffered from brain injury. There is evidence that brain death causes inflammatory changes in the donor. To define the impact of brain death, we evaluated the gene expression of cytokines in human brain dead and ideal living donors and compared these data to organ function following transplantation.

In a previous study, structural myocardial damage was found to occur in 60% of baboons after brain death had been induced by a rapid increase in intracranial pressure. In the present study, we attempt to clarify the causative mechanisms involved in the development of such injury. Three groups of baboons were subjected to brain death: group A, the control; group B, those with previous surgical or pharmacological cardiac sympathectomy or cardiac denervation; and group C, those with bilateral vagotomy, incomplete sympathectomy, or bilateral adrenalectomy. Electrocardiographic and hemodynamic responses to brain death were greatly modified in group B baboons compared with responses in groups A and C. Groups A and C showed a high incidence of myocardial necrosis, whereas no myocyte damage was seen in the hearts of group B baboons. The histological appearance of innervated hearts following brain death (groups A and C) may closely resemble that seen during an acute rejection episode following cardiac transplantation. We suggest that myocardial damage occurring during the process of dying may be related to endogenous catecholamine release (possibly resulting in increased calcium uptake by the myocardial cells), inducing various forms of myocyte necrosis. This may result in early failure in a donor heart following cardiac transplantation.

Background-Donor brain death upregulates expression of inflammatory mediators in the heart. It is hypothesized that these nonspecific changes trigger and amplify acute rejection in unmodified recipients compared with hearts from normal living donors. We examined the inflammatory and immunological consequences of gradual-onset donor brain death on cardiac allografts after transplantation. Methods and Results-Functioning hearts were engrafted from normotensive donors after 6 hours of ventilatory support.

Since endothelins were discovered by Yanasigawa in 1988 it has been recognised that they may have an important role in lung pathophysiology. Despite their biological importance as vasoconstrictors the physiological role of endothelin has not yet been de®ned within the lungs. This review explores their role in acute and chronic disease. During acute in¯ammation and ischaemia±reperfusion injury cytokines may induce release of endothelin. This is important in the realm of acute lung injury and during surgical procedures such as cardiopulmonary operations including lung resections and transplantation. Complications of surgery including primary organ failure resulting in poor gas exchange as well as increased pulmonary vascular resistance have been linked to the presence of excessive endothelin. Endothelin may have an important role in transplantation biology. The complex process leading to successful lung transplantation includes optimising the donor with brain death, harvesting the lungs, managing acute and chronic rejection, and protecting the vital organs from toxic eects of immunosuppressants. During chronic disease processes, the mitotic action of endothelin may be important in vascular and airway remodelling by means of smooth muscle cell proliferation. We also explore recent advances in drug development, animal models and future directions for research.

Solid organ donation is a valuable method of treating various end-stage diseases in adults and ~hildren.7~ Already in the early days of transplantation, organ shortage was recognized as the major obstacle to offering this treatment to patients in need.30 As survival rates improve, more indications for organ transplantation become evident. Because organ availability does not equal organ need, waiting lists and waiting times have increased dramatically over the past decade, confronting physicians with an ever-increasing moral dilemma to which developing countries long have been accustomed: not being able to help, despite knowing how to help. Although new ways of tackling the organ shortage appropriately are sought by expanding living related transplantation and nonheart-beating donors, cadaveric heart-beating organ donation always will be of crucial importance as a source of organs. The current situation, with annual organ donation rates compared with waiting lists and annual deaths of people waiting for an organ, is presented in . From 5% (Europe), to 10% (United Kingdom), to 19% (United States) (all in 1998) of all donors are children. Although, in earlier years, organs from young children often were not transplanted because of less favorable results, this situation has improved markedly,Is2 and pediatric organs are used for pediatric and adult recipients,", lz8, 141, lS9 while even more adult organs serve pediatric recipients.

Background: The sequelae of severe brain injury include myocardial dysfunction. We sought to describe the prevalence and characteristics of myocardial dysfunction seen in the context of brain-injury-related brain death and to compare these abnormalities with myocardial pathologic changes. Methods: We examined the clinical course, electrocardiograms, head computed tomography scans, and echocardiographic data of 66 consecutive patients with brain death who were evaluated as heart donors. In a subgroup of patients, we compared echocardiographic findings with pathologic findings. Results: Echocardiographic systolic myocardial dysfunction was present in 28 (42%) of 66 patients and was not predicted by clinical, electrocardiographic, or head computed tomographic scan characteristics. Ventricular arrhythmias were more common in the patients with, compared to those without, myocardial dysfunction (32% vs 0%; p Ͻ 0.001). Myocardial dysfunction was segmental in all 8 patients with spontaneous subarachnoid or intracerebral hemorrhage. In these patients, the left ventricular apex was often spared. Myocardial dysfunction was either segmental or global in 17 patients who suffered head trauma and in 3 patients who died of other central nervous system illnesses. In 11 autopsied hearts, we found poor correlation between echocardiographic dysfunction and pathologic findings. Conclusions: Systolic myocardial dysfunction is common after brain-injury-related brain death. After spontaneous subarachnoid or intracerebral hemorrhage, the pattern of dysfunction is segmental, whereas after head trauma, it may be either segmental or global. We found poor correlation between the echocardiographic distribution of dysfunction and light microscopic pathologic findings.

I n collaboration with the Canadian Critical Care Society, the Canadian Association of Transplantation and the Canadian Society of Transplantation, the Canadian Council for Donation and Transplantation (CCDT) sponsored a forum entitled "Medical Management to Optimize Donor Organ Potential," 23-25 Feb. 2004, to develop guidelines and recommendations for organ donor management in Canada. Discussions were restricted to the interval of care that begins with neurological determination of death (NDD), commonly called "brain death," and consent to organ donation, and culminates in surgical organ procurement. This period presents a significant opportunity to enhance multi-organ function and improve organ utilization. The forum was the first structured, cooperative assembly of health professionals in the fields of critical care and transplantation and can be viewed as a landmark event in Canada. End-of-life care in the intensive care unit (ICU) includes all efforts to actualize the desire and opportunity to donate organs. The evolving collaboration to establish best donor management practices in the ICU and operating room must be accompanied by efforts to ensure optimum organ utilization. In turn, improving the use of organs must be linked with improving transplant graft and patient outcomes. Process Substantive background documents, provided by the steering committee in advance of the forum included comprehensive

Aims/hypothesis We examined the presence of functional cannabinoid receptors 1 and 2 (CB1, CB2) in isolated human islets, phenotyped the cells producing cannabinoid receptors and analysed the actions of selective cannabinoid receptor agonists on insulin, glucagon and somatostatin secretion in vitro. We also described the localisation on islet cells of: (1) the endocannabinoid-producing enzymes N-acyl-phosphatidyl ethanolamine-hydrolysing phospholipase D and diacylglycerol lipase; and (2) the endocannabinoid-degrading enzymes fatty acid amidohydrolase and monoacyl glycerol lipase. Methods Real-time PCR, western blotting and immunocytochemistry were used to analyse the presence of endocannabinoid-related proteins and genes. Static secretion experiments were used to examine the effects of activating CB1 or CB2 on insulin, glucagon and somatostatin secretion and to measure changes in 2-arachidonoylglycerol (2-AG) levels within islets. Analyses were performed in isolated human islets and in paraffin-embedded sections of human pancreas. Results Human islets of Langerhans expressed CB1 and CB2 (also known as CNR1 and CNR2) mRNA and CB1 and CB2 proteins, and also the machinery involved in synthesis and degradation of 2-AG (the most abundant endocannabinoid, levels of which were modulated by glucose). Immunofluorescence revealed that CB1 was densely located in glucagon-secreting alpha cells and less so in insulin-secreting beta cells. CB2 was densely present in somatostatin-secreting delta cells, but absent in alpha and beta cells. In vitro experiments revealed that CB1 stimulation enhanced insulin and glucagon secretion, while CB2 agonism lowered glucose-dependent insulin secretion, showing these cannabinoid receptors to be functional. Conclusions/interpretation Together, these results suggest a role for endogenous endocannabinoid signalling in regulation of endocrine secretion in the human pancreas.

It is widely recognized that living-related donor (LRD) renal allografts have a higher overall graft survival than cadaver donor transplants. We tested the hypothesis that part of this is attributable to LRD kidneys being obtained under optimal conditions from healthy donors, whereas ...

We hypothesized that increased levels of blood cytokines occur in brain-dead patients, and that these cytokines are responsible for some of the endocrine and/or acute-phase reactant abnormalities found in these patients. We measured blood levels of cytokines, hormones, and acute-phase reactants in 18 brain-dead potential organ donors at the moment of establishing the legal diagnosis of brain death and compared them with levels found in a control group. Although interleukin-l~ (IL.I~) and tumor necrosis factor-alpha (TNF-~) levels were within the normal range, interleukin-6 (IL-6) levels were clearly above the normal range in all patients (median, 1,444 pg/mL; range, 75 to 11,780}. In the brain-dead group, total thyroxine (tT4), free 1"4 (fT4), triiodothyronine (T3), thyrotropin (TSH), dehydroepiandrosterone sulfate (DHEA-S), testosterone, albumin, Zn, and osteocalcin levels were decreased, T3 resin uptake index (T3 RUI), corticotropin (ACTH}, cortisot, 11-deoxycortisol (11-DOC), 17-hydroxyprogesterone (17-OHPr), aldosterone, luteinizing hormone, and follicle-stimulating hormone levels were normal, and reverse T3 (rT3), renin, and C-reactive protein (CRP) levels were increased. Multiple regression analysis demonstrated significant interrelations between IL-6 and 1"4, T3, testosterone, and CRP. We also studied the evolution of some of these parameters in four patients with severe head injury who finally developed brain death. IL-6 levels on admission to the intensive care unit (ICU) were above the normal limits, as in other patients with cranial trauma, but when the patients developed brain death, there was a pronounced increase in IL-6 levels. We conclude that brain death is accompanied by high levels of IL-6. IL.6 may be partially responsible for the hormonal and acute-phase reactant abnormalities found in these patients.

The clinical observation that the results of kidney grafts from living donors (LD), regardless of relationship with the host, are consistently superior to those of cadavers suggests an effect of brain death (BD) on organ quality and function. This condition triggers a series of nonspecific inflammatory events that increase the intensity of the acute immunologic host responses after transplantation (Tx). Herein are examined the influences of this central injury on late changes in renal transplants in rats. A standardized model of BD was used. Groups included both allografts and isografts from normotensive braindead donors and anesthetized LD. Renal function was determined every 4 wk after Tx, at which time representative grafts were examined by morphology and by reverse transcriptase-PCR. Long-term survival of brain-dead donor transplants was

Although ϳ1 million islets exist in the adult human pancreas, current pancreas preservation and islet isolation techniques recover <50%. Presently, cadaveric donors remain the sole source of pancreatic tissue for transplantation. Brain death is characterized by activation of proinflammatory cytokines and organ injury during preservation and reperfusion. In this study, we assessed the effects of brain death on islet isolation yields and functionality. Brain death was induced in male 250-to 350-g Lewis rats by inflation of a Fogarty catheter placed intracranially. The rats were mechanically ventilated for 2, 4, and 6 h before removal of the pancreas (n ‫؍‬ 6). In controls, the catheter was not inflated (n ‫؍‬ 6). Shortly after brain death induction, a significant increase in serum tumor necrosis factor-␣ (TNF-␣), interleukin (IL)-1␤, and IL-6 was demonstrated in a time-dependent manner. Upregulation of TNF-␣, IL-1␤, and IL-6 mRNA was noted in the pancreas. Brain death donors presented lower insulin release after glucose stimulation assessed by in situ perfusion of the pancreas. Islet recovery was reduced in brain death donors compared with controls (at 6 h 602.3 ؎ 233.4 vs. 1,792.5 ؎ 325.4 islet equivalents, respectively; P < 0.05). Islet viability assessed in dissociated islet cells and in intact cultured islets was reduced in islets recovered from brain death donors, an effect associated with higher nuclear activities of NF-B p50, c-Jun, and ATF-2. Islet functionality evaluated in vitro by static incubation and in vivo after intraportal transplantation in syngeneic streptozotocin-induced diabetic rats was significantly reduced in preparations obtained from brain death donors. In conclusion, brain death significantly reduced islet yields and functionality. These observations may lead to strategies to reduce the effects of brain death on pancreatic islets and improve the results in clinical transplantation. Diabetes 52: [2935][2936][2937][2938][2939][2940][2941][2942] 2003

Although the focus is allograft rejection, some illustrato injury sustained during the transplant process? Allograft tions are taken from models of the immune response rejection can be caused by numerous factors such as damage against infections because over the course of time, the to the donor kidney during surgical removal or implantation, immune response evolved, not to reject allografts, but injury sustained during the transport process between the doto defend against infections [14]. Thus, the same rules nor and recipient, and suboptimal allograft perfusion during the intra-and post-operative period. In cadaveric allografts,

✓ To investigate the hemodynamics of intracranial circulatory arrest, the authors correlated the findings of noninvasive transcranial Doppler ultrasonography (TCD) with those of transfemoral four-vessel angiography in 65 patients following brain death and intracranial circulatory arrest due to severe intracranial hypertension. The three TCD stages of intracranial circulatory arrest, which have been described previously, corresponded with different levels of extracerebral angiographic cessation of flow. With TCD progression from the first stage (oscillating flow) to the third stage (no flow), the level where the dye stopped descended caudad from subarachnoid to cervical levels. The study shows that, in progressing intracranial hypertension, arterial circulatory standstill within the cranial cavity develops in a distal-to-proximal direction. The basal cerebral arteries remain patent in the early stages of intracranial circulatory arrest. Experimental evidence from the literature, toge...

The brain is the exclusive or almost exclusive site of formation of 24S-hydroxycholesterol and we have shown that the circulating level of 24S-hydroxycholesterol is dependent upon the relation between cerebral production and hepatic clearance. In the present work we determined plasma levels of 24S-hydroxycholesterol in patients with various neurological diseases. Eleven subjects with brain death occurring 6±10 h before collection of the plasma samples had markedly reduced circulating levels of 24S-hydroxycholesterol (243%, P , 0:001). Patients with advanced Alzheimer's disease and cerebral in¯ammatory diseases had slightly lower levels of 24S-hydroxycholesterol in plasma when compared to matched controls. Patients with acute ischemic stroke, multiple sclerosis and primary brain tumors had levels not signi®cantly different from those of controls. The conditions leading to reduced plasma levels of 24S-hydroxycholesterol had no signi®cant effect on plasma levels of another side-chain oxidized oxysterol, 27-hydroxycholesterol. Except for conditions characterized by very marked destruction of the central nervous system, different severe neurological diseases seem to have relatively small effects on the¯ux of 24S-hydroxycholesterol from the brain. q

Objectives: We review our surgical experience patients with atriopulmonary Fontan operations who had obstructive or arrhythmia indications for conversion to total cavopulmonary artery connections, arrhythmia circuit cryoablation, and placement of atrial antitachycardia pacemaker. Methods: Fourteen patients (mean age 14 ؎ 4 years) had conversion to total cavopulmonary artery connection 8 ؎ 3 years after the original atriopulmonary Fontan operation primarily for atrial arrhythmias in 11, obstructive lesions in 2, and bradycardia with cyanosis in 1. Arrhythmia circuit cryoablation was performed on 11 patients and 10 had atrial antitachycardia pacemakers. Preoperative functional New York Heart Association class was IV in 9, III in 4, and II in 1. Results: One patient had brain death (7%) presumably caused by resternotomy complications despite an excellent hemodynamic result. Another required reoperation for a maldeployed clamshell device after attempted fenestration closure. Average length of stay was 10 ؎ 3 days; chest tubes were removed on day 7 ؎ 3. There were no long-term deaths (mean follow-up 1.7 years, range 5 months to 5 years).