The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression.

Posttransplant lymphoproliferative disorders (PTLDs) were diagnosed in 43 patients from the Pittsburgh-Denver series between June 1980 and March 1987. This constitutes a detection rate of 1.7%. Major categories of clinical presentation included a mononucleosislike syndrome, gastrointestinal/abdominal disease, and solid organ disease. The median time of onset in patients initially immunosuppressed with cyclosporine-A (CsA)-containing regimens was 4.4 months after transplant, regardless of tumor clonality. A strong association of PTLD with Epstein-Barr virus (EBV) was observed. A histologic spectrum of lesions from polymorphic to monomorphic was observed. Whereas polymorphic lesions could be either clonal or nonclonal, monomorphic lesions appeared to be clonal in composition. The presence of large atypical cells (atypical immunoblasts) or necrosis did not appreciably worsen the prognosis. Twelve patients had clonal, 13 had nonclonal, and five had both clonal and nonclonal tumors. Clonality was indeterminate in 13 cases. Most patients were treated with a regimen based on reduced immunosuppression and supportive surgery. Almost all nonclonal and about half of the clonal lesions respond to this conservative therapy, indicating that it is an appropriate first line of treatment. This behavior suggests that a spectrum of lesions ranging from infectious mononucleosis to malignant lymphoma constitutes the entity known as PTLD. Some monoclonal tumors can undergo regression, however, apparently in response to host immune control mechanisms. Because of its short latency and strong association with EBV, PTLD is an important model for the study of virus-associated tumor progression in humans.     

Donor gender does not affect liver transplantation outcome in children

The liver is recognized as a sex hormone-responsive organ. Gender-specific differences in liver function are known to exist. Recently, a higher failure rate for organs transplanted in adults from female donors to male recipients has been reported. This increased failure rate of livers obtained from adult females and transplanted into adult males is thought to occur, at least in part, as a result of intrinsic gender-specific differences in hepatocyte cell surface expression and to alterations in the hormonal milieu of the donor liver in the recipient. To determine whether the same graft-recipient gender-determined failure rates pertain in the pediatric liver transplant population, the outcome of 335 primary liver transplants performed in children at the University of Pittsburgh Medical Center was examined. No difference in transplant outcome was demonstrated in children based on the gender pairings between the donor and recipient whether or not variables such as the age, etiology of the liver disease, and the blood group of the recipient were included in the data analysis. Thus, in contrast, to the situation in adults, the gender of the donor does not influence the outcome of liver transplantation in children and should not be used as a criterion for donor selection. This difference between adults and children may be due, at least in part, to gender differences in hepatocyte phenotypic expression induced as a consequence of puberty.Supported by Research Grants from the Veterans Administration Project grant DK 29961 from the National Institutes of Health NIDDK 32556.     

保健食品微生物限度检查的方法学验证

目的:确认对保健食品进行微生物限度检查时,昕采用的细菌、霉菌及酵母菌计数和控制菌检查方法是否适合于该保健食品的微生物限度检查。方法:按2005年版中国药典微生物限度检查法及方法学验证实验要求,对21种保健食品进行了方法学验证。结果:10个品种(血尔口服液、金舒通胶囊、事轻松胶囊、梦玉胶囊等)分别对金黄色葡萄球菌和枯草芽孢杆菌有明显的抑菌作用,阳性对照菌回收率均低于70%。结论:保健食品采用 GB/T4789-2003食品卫生微生物学检查法进行检查时,其检验结果可能不够科学,建议参照2005年版中国药典要求,通过方法验证实验建立合理的检验方法。     

The many faces of multivisceral transplantation

The transplantation of multiple abdominal viscera, including liver-duodenum-pancreas, liver-stomach-duodenum-pancreas and liver-intestine, is being performed with increasing frequency and success. These procedures and other variations are derived from a seldom used multivisceral operation in which all of the foregoing organs are transplanted en bloc. It is described herein how the full multivisceral transplantation and its less extensive derivatives are based on the same principles of procurement, preservation and postoperative management. With all of these multiple organ permutations and with intestinal transplantation alone, management is complicated by inclusion in the grafts of a large lymphoreticular component that is capable of causing graft versus host disease (GVHD). Because of a systematic error in therapeutic philosophy, past efforts have been directed at altering or damaging the lymphoreticular cells by pretreatment of the donor or of the organs with drugs, irradiation or other means. From recent observations, the alternative approach is suggested of keeping these lymphoid depots intact, which then become the site of two way cell traffic after transplantation. With the use of powerful immunosuppression, such as that provided with FK 506, the donor lymphoreticular cells can circulate in the recipient without causing clinical GVHD, and the lymphoreticular cells in the graft become those of the recipient (local chimerism) without causing rejection. Even with avoidance of rejection and GVHD, metabolic interrelations between the grafted organs, and also between the graft organs and retained recipient viscera can affect the fate of the individual transplanted organs or retained recipient organs. The best delineated of these metabolic influences are mediated by the endogenous splanchnic hepatotrophic factors, of which insulin has been the most completely studied. An understanding of these various immunologic and nonimmunologic factors combined with more potent immunosuppression that is now available is sure to stimulate efforts at transplantation of abdominal organs and particularly of the hollow viscera that have resisted such clinical efforts.     

Mechanisms of hypertension during and after orthotopic liver transplantation in children

The aim of this study was to assess the hormonal alterations that may mediate the systemic hypertension that develops in patients during the perioperative period of orthotopic liver transplantation. We studied nine pediatric patients without previous hypertension or renal disease during six time points, starting before transplantation and ending at 48 hours after surgery. Hypertension developed in all patients in association with central venous pressures less than 10 mm Hg. Free water clearance was negative in all nine patients. Vasopressin levels increased intraoperatively but fell as hypertension developed. Atrial natriuretic factor levels increased as systemic blood pressure rose. A high level of plasma renin activity was observed in four patients with renal insufficiency. In six patients, postoperative 24-hour urinary norepinephrine excretion was within the normal age-adjusted range. These findings suggest that the combination of cyclosporine, corticosteroids, and, in some patients, an elevated plasma renin activity prevents the kidney from responding to the acute volume and salt overload with an appropriate diuresis and natriuresis, thus leading to systemic hypertension. The treatment of hypertension after liver transplantation may include salt restriction, diuretics, and, in those patients with a low creatinine excretion index, angiotensin coverting enzyme inhibitors.     

Marked transient alkaline phosphatemia following pediatric liver transplantation

An isolated marked transient rise in serum alkaline phosphatase levels in otherwise healthy children is a well-documented occurrence. However, in children undergoing liver transplantation, elevated alkaline phosphatase values raise the possibility of biliary obstruction, rejection, or both. During a 6-year period, 6 of 278 children undergoing liver transplantation exhibited a similar phenomenon as an isolated abnormality. None had rejection, biliary obstruction, or other allograft dysfunction during a long follow-up. Eventually and without intervention, the alkaline phosphatase levels returned to normal. These instructive cases suggest that caution be used in advocating invasive procedures if elevated alkaline phosphatase levels are an isolated abnormality, and close observation with noninvasive testing is recommended.     

Selenium status of New Zealand infants fed either a selenium supplemented or a standard formula

Objective: New Zealand soils are deficient in the essential micronutrient, selenium. New Zealand infants have low selenium levels at birth and experience a further decline if fed cows milk based formula. This study examined the selenium status of infants fed with a new commercially available selenium supplemented formula.
Methodology Forty-four newborn infants, whose mothers wished to formula feed, were randomized in an open controlled trial to be fed a commercially available selenium supplemented cows milk formula (containing 17 μg Se/L) or an unsupplemented formula (containing 4.6 μg Se/L). Cord, 1 and 3 month blood samples were obtained for selenium status (plasma and red cell selenium and glutathione peroxidase) and thyroid function.
Results Mean plasma selenium and glutathione peroxidase values were significantly higher in supplemented than unsupplemented infants at 1 month (unpaired t -tests; P <0.0001 and P = 0.001 respectively) and 3 months ( P <0.0001 and P = 0.0005). Analysis within treatment groups between time points (paired t -tests) showed that selenium supplementation prevented the fall in plasma selenium from birth to 1 month seen in unsupplemented infants and was associated with a rise in levels between 1 and 3 months ( P = 0.002).
Conclusions Supplementing cows milk formula with selenium to replicate the levels found in breast milk is nutritionally sound. Feeding from a few days of age with a formula containing 17 μg Se/L in infants with low selenium status at birth is sufficient to cause a rise to 80% of adult levels at 3 months of age.     

A simplified technique for revascularization of homografts of the liver with a variant right hepatic artery from the superior mesenteric artery

A simplified technique for conversion of a complex hepatic arterial supply into a common channel is described. This technique permits single vessel anastomosis in the recipient of a liver transplant.     

Low flow venovenous bypasses in small dogs and pediatric patients undergoing replacement of the liver

A venovenous bypass for transplantation of the liver was developed and evaluated in dogs and applied clinically, with flows that averaged less than 500 milliliters per minute. Fatal pulmonary emboli were seen in two of 40 experiments. The venovenous flow in the four pediatric recipients was 200 to 1,200 milliliters per minute, and there were no complications.