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.
From the 355 consecutive brain dead cadaveric organ donors procured at our center in the last four years, 2000–2003, four of them (1.1%) had bacterial endocarditis as cause of death. The bacteria responsible for the endocarditis were Staphylococcus epidermidis, coagulase-negative Staphylococcus , Staphylococcus hominis and Streptococcus viridans , respectively. We performed five kidney and two liver transplantations on seven recipients. All donors and recipients received antibiotic treatment against the germ causing the respective endocarditis.
Infection by the bacteria responsible for the endocarditis in the respective donors was not transmitted to any of the recipients. Six of the seven recipients were alive with normal-functioning grafts after between 13 and 24 months' follow-up. Transplantectomy was performed on one kidney recipient due to thrombosis of the renal vein of the graft not related to the endocarditis.
Liver and kidney transplantation from donors dying from bacterial endocarditis can be performed without causing the transmission of infection to the recipient or the dysfunction of the graft.     

The Hemodynamic Mechanisms of Lung Injury and Systemic Inflammatory Response Following Brain Death in the Transplant Donor

Brain-dead donors are the major source of lungs for transplantation. Brain death is characterized by two hemodynamic phases. Initially, massive sympathetic discharge results in a hypertensive crisis. This is followed by neurogenic hypotension. Up-regulation of pro-inflammatory mediators occurs in all organs and lung injury develops; this can adversely affect graft function post-transplantation. The mechanisms of the systemic and lung inflammation are unknown. We hypothesized that the hemodynamic changes are responsible for these inflammatory phenomena. Brain death was induced by intra-cranial balloon inflation in rats. This resulted in hypertensive crisis, followed by hypotension. There was a significant increase in blood neutrophil CD11b/CD18 expression and pro-inflammatory cytokine levels in serum and bronchoalveolar lavage, compared with control animals. Rupture of the capillary-alveolar membrane was demonstrated by electron microscopy. Elimination of the hypertensive response by α-adrenergic antagonist pre-treatment prevented inflammatory lung injury, reduced the systemic inflammatory markers and preserved capillary-alveolar membrane integrity. Correction of the neurogenic hypotension with noradrenaline ameliorated the systemic inflammatory response and improved oxygenation. We conclude that the sympathetic discharge triggers systemic and lung inflammation, which can be further enhanced by neurogenic hypotension. Management of the brain-dead donor with early anti-inflammatory treatment and vasoconstrictors is warranted.     

Segmental Liver Transplantation from Non-Heart Beating Donors—An Early Experience with Implications for the Future

We report our experience of pediatric liver transplantation with partial grafts from non-heart beating donors (NHBD). Controlled donors less than 40 years of age with a warm ischemia time (WI) of less than 30 min were considered for pediatric recipients. Death was declared 5 min after asystole. A super-rapid recovery technique with aortic and portal perfusion was utilized. Mean donor age was 29 years and WI 14.6 min (range 11–18). Seven children, mean age 4.9 years (0.7–11), median weight 20 kg (8.4–53) received NHBD segmental liver grafts. Diagnoses included seronegative hepatitis, neonatal sclerosing cholangitis, familial intrahepatic cholestasis, hepatoblastoma, primary hyperoxaluria and factor VII deficiency (n = 2).The grafts included four reduced and one split left lateral segments, one left lobe and one right auxiliary graft. Mean cold ischemia was 7.3 h (6.2–8.8). Complications included one pleural effusion and one biliary collection drained percutaneously. At 20 months (10–36) follow-up all children are alive and well with functioning grafts.
Donation after cardiac death is a significant source of liver grafts for adults and children with careful donor selection and short cold ischemic times.     

Cigarette smoke toxicants alter growth and survival of cultured mammalian cells.

Our purpose was to determine the effects of six cigarette toxicants (pyridine, nicotine, 2-ethylpyridine, 3-ethylpyridine, p-cresol, and pyrazine) on three types of cultured mammalian cells (human umbilical vein endothelial cells [HUVECs], human microvascular endothelial cells [HMVECs], and NIH 3T3 cells) using a cell proliferation/survival assay. Synchronized cells were cultured in proliferation or survival medium containing various doses (10(-18)M-10(-2)M) of the tested chemicals. After 48 h, cells were counted using a hemacytometer. The no observable adverse effect level (NOAEL), lowest observable adverse effect level (LOAEL), and the efficacy were determined for each compound in the cell proliferation and survival assays. Pyridine and p-cresol did not show significant effects with any cell types, except at high doses. Derivitization of the pyridine ring altered its potency, especially when an ethyl group or nitrogen was added. In survival medium, nicotine stimulated proliferation of all three cell types at doses found in smoker's serum (10(-8)M-10(-7)M). For HUVEC and HMVEC, 2-ethylpyridine, 3-ethylpyridine, and pyrazine inhibited proliferation in proliferation medium and induced cell death in survival medium at attomolar and femtomolar doses. All chemicals, except pyridine and pyrazine, stimulated NIH 3T3 cell proliferation at low doses and induced cell death at high doses. LOAELs and efficacies revealed that endothelial cells from a developing organ (umbilical cord) were more sensitive to these chemicals than endothelial cells from an adult organ (lung). 3-Ethylpyridine and pyrazine, which induced cell death at low doses, are added to consumer products and should be subjected to further toxicological testing.     

老年性痴呆的病理特征与防治对策

老年痴呆症的发生与AB以及Tau蛋白的错误折叠密切相关，是蛋白质折叠相关的疾病，早期诊断是预防老年痴呆症的首要任务，而综合治疗是人类对抗老年痴呆症的必然举措。     

Fifteen-year follow-up of 92 hospitalized adults with Down's syndrome: incidence of cognitive decline, its relationship to age and neuropathology

Background The clinical and neuropathological features associated with dementia in Down’s syndrome (DS) are not well established. Aims To examine clinico‐pathological correlations and the incidence of cognitive decline in a cohort of adults with DS. Method A total of 92 hospitalized persons with DS were followed up from 1985 to December 2000. At outset, 87 participants were dementia‐free, with a median age of 38 years. Assessments included the Prudhoe Cognitive Function Test (PCFT) and the Adaptive Behavior Scale (ABS), to measure cognitive and behavioural deterioration. Dementia was diagnosed from case records and caregivers’ reports. Results Eighteen (21%) patients developed dementia during follow‐up, with a median age of onset 55.5 years (range 45–74). The PCFT demonstrated cognitive decline among those with a less severe intellectual disability (mild and moderate) but not among the profoundly disabled people (severe and profound). Clinical dementia was associated with neuropathological features of Alzheimer’s disease, and correlated with neocortical neurofibrillary tangle densities. At the age of 60 years and above, a little more than 50% of patients still alive had clinical evidence of dementia. Conclusions Clinical dementia associated with measurable cognitive and functional decline is frequent in people with DS after middle age, and can be readily diagnosed among less severely intellectually disabled persons using measures of cognitive function such as the PCFT and behavioural scales such as the ABS. In the more profoundly disabled people, the diagnosis of dementia is facilitated by the use of behavioural and neurological criteria. In this study, the largest prospective DS series including neuropathology on deceased patients, the density of neurofibrillary tangles related more closely to the dementia of DS than senile plaques. In people with DS surviving to middle and old age, the development of dementia of Alzheimer type is frequent but not inevitable, and some people with DS reach old age without clinical features of dementia.     

Intrauterine position affects motoneuron number and muscle size in a sexually dimorphic neuromuscular system

The intrauterine position occupied by a rodent fetus influences the amount of testosterone to which it is exposed before birth. Animals that are gestated between two male fetuses (2M) are exposed to higher circulating levels of testosterone than are animals positioned between two female fetuses (2F) and there are reliable differences in the reproductive physiology and behavior of 2M and 2F animals when adult. To determine whether intrauterine position modifies development of the central nervous system, we examined the sexually dimorphic spinal nucleus of the bulbocavernosus (SNB) in male and female gerbils from known intrauterine positions. We found that adult 2M female gerbils had 16% more SNB motoneurons than did 2F females. 2M males did not differ from 2F males in SNB motoneuron number, but the bulbocavernosus muscle, which is innervated by SNB motoneurons, was approximately 50% larger in 2M than in 2F males. These data indicate that intrauterine position can influence the morphology of the sexually dimorphic SNB neuromuscular system.     

Outcome in Children With Significantly Abnormal Cerebral Blood Flow Detected by Doppler Ultrasonography: Focus on the Survivors

BACKGROUND AND PURPOSE: The Doppler waveform patterns of loss of diastolic flow, appearance of retrograde diastolic flow, or no detectable flow in the cerebral arteries suggest significantly abnormal cerebral blood flow (CBF). A retrospective study was performed to show that significantly abnormal CBF alone, without clinical criteria, is not necessarily specific to brain death in the young pediatric population. PATIENTS AND METHODS: Forty-seven pediatric patients, from newborn to 4 years of age, were found to have significantly abnormal CBF, including 7 patients with loss of diastolic flow, 28 with retrograde diastolic flow, and 23 with no detectable cerebral flow on serial Doppler sonographic examinations. Their clinical data and sonographic results were collected and analyzed. RESULTS: Forty-two patients died, a few of whom had only transient improvement of cerebral flow. All of the patients with no detectable cerebral flow expired. Five patients survived with or without sequelae. Their underlying conditions that caused increased intracranial pressure were treated by medical and/or surgical intervention, and diastolic reversal of CBF corrected within 1 day in all 5. CONCLUSIONS: Although no detectable flow is a lethal sign, pediatric patients with loss or reversal of diastolic flow may survive with prompt and effective treatment. Using Doppler ultrasound to diagnose cerebral circulatory arrest should be done with caution in pediatric patients.