Kidney,Pancreas and Liver Allocation and Distribution in the United States

Kidney transplant and liver transplant are the treatments of choice for patients with end‐stage renal disease and end‐stage liver disease, respectively. Pancreas transplant is most commonly performed along with kidney transplant in diabetic end‐stage renal disease patients. Despite a steady increase in the numbers of kidney and liver transplants performed each year in the United States, a significant shortage of kidneys and livers available for transplant remains. Organ allocation is the process the Organ Procurement and Transplantation Network (OPTN) uses to determine which candidates are offered which deceased donor organs. OPTN is charged with ensuring the effectiveness, efficiency and equity of organ sharing in the national system of organ allocation. The policy has changed incrementally over time in efforts to optimize allocation to meet these often competing goals. This review describes the history, current status and future direction of policies regarding the allocation of abdominal organs for transplant, namely the kidney, liver and pancreas, in the United States.     

Randomized clinical trial of ganciclovir vs acyclovir for prevention of cytomegalovirus antigenemia after allogeneic transplantation

Cytomegalovirus (CMV) disease remains a major cause of morbidity following allogeneic stem cell transplantation (SCT). In a prospective randomized trial, we tested prophylactic therapy with ganciclovir or acyclovir for patients at high risk of disease. Ninety-one CMV seropositive recipients of related (n = 53) and unrelated (n = 38) donor transplants were enrolled. All patients received intravenous (i.v.) ganciclovir 5 mg/kg every 12 h days -7 to -2, followed by acyclovir 10 mg/kg i.v. every 8 h from day -1 until neutrophil engraftment. Patients were then randomly assigned to either ganciclovir (n = 45) or acyclovir (n = 46) until day 100 post transplant. Any degree of antigenemia was treated with ganciclovir 5 mg/kg i.v. twice a day for 2 weeks, followed by 5 mg/kg i.v. each weekday for 6 weeks. At day 100, the cumulative incidence of antigenemia was 31% (95% CI 17-45%) for ganciclovir and 41% (95% CI 26-56%) (P = 0.22) for acyclovir prophylaxis, respectively. The assigned prophylaxis cohort did not predict for CMV antigenemia. The cumulative incidence of CMV disease at 12 months was 13% (95% CI 3-23%) and 17% (95% CI 6-28%) (P = 0.59) for the ganciclovir- and acyclovir-treated groups, respectively. An absolute neutrophil count (ANC) 相似文献   

Venous isthmus plasty for coarctation of inferior venacava

A male aged 40, presented with hour glass type of obstruction of the supra hepatic segment of the inferior venacava (ivc). This segment was exposed by a posterolateral thoracotomy. A linear venotomy after proximal and distal clamping revealed a shelf like fibrous tissue obstructing the venacava. This shelf was excised. Venotomy was closed using a patch of Goretex graft. Immediate postoperative follow up is gratifying with patentivc. This is a new surgical approach for coarctation ofivc.     

Etiological agents of acute poliomyelitis in South India

This study was done to identify the specific etiological agents that cause acute poliomyelitis (APM). All the children newly diagnosed clinically as APM at the Institute of Child Health, Madras, during the period May 1988 to May 1989 were recruited. Stool specimen collection, transportation and identification of viruses by culture were done by standard procedures. The total number of children recruited was 312. Specimens were contaminated/insufficient in 10. Analysis was done for 302 cases. Polio virus type II was identified in 25.5% children, type I in 18.5%, type III in 15.9%, multiple polioviruses in 6.3% and non-polio enteroviruses (NPEV) in 20.2% cases. No virus was identified in 13.6%. Among the APM cases clinically diagnosed, the proportion of NPEV has increased considerably from 5% in 1984 to 20.2% in 1988–89. The age distribution was not significantly different between polio viruses and NPEV. The distribution of polio viruses and NPEV did not differ significantly in relation to immunization status, source of water supply, method of excreta disposal and the clinical types. For surveillance and control/eradication program of poliomyelitis, laboratory confirmation is essential.     

Risk factors for rising creatinine in renal allografts with 1 and 3 yr survival

BACKGROUND: Determining factors associated with negative slope of inverse creatinine vs. time (1/Cr vs. t) may help prevent a decline in renal allograft function. METHODS: A total of 1389 adult recipients of primary renal transplants were divided into quartiles based on the slope of 1/Cr vs. t calculated from 6 and 12 months post transplant. A multivariate analysis of risk factors for being in the worst vs. best quartile employed these variables: donor source, HLA mismatch, recipient age, donor age, panel-reactive antibody (PRA), acute rejection (AR), 3-month cyclosporin A (CsA) level, 1-yr CsA level and acute tubular necrosis. Two separate analyses compared risk factors in patients with 1 and 3 yr survival, respectively. RESULTS: In recipients with > or = 1 yr graft survival, high PRA and AR were associated with negative slopes of 1/Cr vs. t. For those with > or = 3 yr graft survival, both AR and 3-month CsA level > 150 ng/mL were significant risk factors, using both 6- and 12-month slopes. Stratification of AR showed 1 AR episode > or = 6 months and multiple AR episodes carried significant risk for negative slopes. CONCLUSION: Optimization of allograft function invokes a conundrum between the needs to avoid both AR and high early CsA levels. We support a policy of carefully balancing these two risks.     

Oxidative and nitrosative stress mediated renal cellular damage induced by cyclosporine A: role of sulphated polysaccharides

Oxidative and nitrosative stress are known to exert various adverse effects on biological systems and this seems to be one of the major contributor of nephrotoxicity induced by cyclosporine A (CsA), which is a major clinical challenge, despite its potent immunosuppressive effect. Sulphated polysaccharides of marine origin are well known for its antioxidant properties, among its other biological applications. CsA administration (25 mg/kg body weight, orally, for 21 d) showed increased level of oxidants and xanthine oxidase activity. CsA induced nitrosative stress was evident from a marked elevation in the expression of inducible nitric oxide synthase mRNA in renal tissue and a concomitant increase in plasma nitric oxide level. Augmented levels of malondialdehyde, 8-hydroxy-2-deoxyguanosine and protein carbonyl coupled with diminished protein thiols; hallmarks of lipid peroxidation, DNA damage and protein oxidation were noted in CsA administered rats. Membrane damage was further confirmed by altered ATPase activities in the renal tissue. Simultaneous treatment with sulphated polysaccharides (5 mg/kg body weight, subcutaneously) remarkably prevented the above alterations mediated by oxidative and/or nitrosative stress during CsA induction. Hence, these findings conclude that the use of an antioxidant agent like sulphated polysaccharides could be a useful tool in reducing CsA-induced nephrotoxicity.     

Polychlorinated Biphenyl (PCBs)-Induced Oxidative Stress Plays a Critical Role on Cerebellar Dopaminergic Receptor Expression: Ameliorative Role of Quercetin

Polychlorinated biphenyls (PCBs) exposure produces profound damage to the developing as well as adult central nervous system. Locomotor activities which are closely linked to dopaminergic neurotransmission are often impaired in PCBs toxicity. Targeting PCBs-induced oxidative stress using natural antioxidants is an attractive approach. Quercetin, a flavonoid is a safe and potent neuroprotective antioxidant. In this study, we sought to examine the protective role of quercetin against PCBs-induced neurodegeneration and dysfunction of dopaminergic receptors in the cerebellar region of adult male rats. They were divided into four groups. Group I received only vehicle (corn oil) intraperitoneally (i.p); Group II received Aroclor 1254 at a dose of 2?mg/kg bwt/day (i.p); Group III received Aroclor 1254 (i.p) and simultaneously quercetin (50?mg/kg bwt/day) through gavage; Group IV received quercetin alone (gavage). After 30?days treatment, rats were euthanized. The cerebellum was dissected from each rat brain, the levels of hydrogen peroxide, lipid peroxidation, protein carbonyl content, and activities of creatine kinase, acetylcholine esterase, membrane-bound ATPases were evaluated. Expressions of dopaminergic receptors and tyrosine hydroxylase in cerebellum were studied by semi-quantitative RT-PCR and western blot analysis, respectively. The PCBs-induced neurodegeneration was assessed by histological studies. Results proclaim that PCBs disturb dopaminergic receptors and also causes neurodegeneration in cerebellum via production of ROS. Simultaneous quercetin treatment had scavenged the free radicals induced by PCBs and protected dopaminergic receptors dysfunction in rat cerebellum.     

Mitochondrial dysfunction in an animal model of hyperoxaluria: a prophylactic approach with fucoidan

Oxalate/calcium oxalate toxicity is mediated through generation of reactive oxygen species in a process that partly depends upon events that induce mitochondrial damage. Mitochondrial dysfunction is an important event favoring stone formation. The objective of the present study was to investigate whether mitochondria is a target for oxalate/calcium oxalate and the plausible role of naturally occurring glycosaminoglycans from edible seaweed, fucoidan in ameliorating mitochondrial damage. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I: vehicle treated control, Group II: hyperoxaluria was induced with 0.75% ethylene glycol in drinking water for 28 days, Group III: fucoidan from F. vesiculosus (5 mg/kg b.wt, s.c) from the 8th day of the experimental period, Group IV: ethylene glycol+fucoidan treated rats. The tricarboxylic acid (TCA) cycle enzymes like succinate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase and respiratory complex enzyme activities were assessed to evaluate mitochondrial function. Oxidative stress was assessed based on the activities of antioxidant enzymes, level of reactive oxygen species, lipid peroxidation and reduced glutathione. Mitochondrial swelling was also analyzed. Ultra structural changes in renal tissue were analyzed with electron microscope. Hyperoxaluria induced a decrease in the activities of TCA cycle enzymes and respiratory complex enzymes. The oxidative stress was evident by the decrease in antioxidant enzymes, glutathione and an increase in reactive species and lipid peroxidation in mitochondria. Mitochondrial damage was evident by increased mitochondrial swelling. Administration of fucoidan, decreased reactive oxygen species, lipid peroxidation (P<0.05), mitochondrial swelling and increased the activities of antioxidant enzymes and glutathione levels (P<0.05) and normalized the activities of mitochondrial TCA cycle and respiratory complex enzymes (P<0.05). From the present study, it can be concluded that mitochondrial damage is an essential event in hyperoxaluria, and fucoidan was able to effectively prevent it and thereby the renal damage in hyperoxaluria.