Trends over a decade of pediatric liver transplantation in the United States.

During the last 10 to 15 years, medical and surgical innovations have established pediatric liver transplantation as the optimal therapy for children suffering acute and chronic liver disease. We hypothesized that the profile of current pediatric liver transplant recipients would differ significantly from that of an earlier era. We collected and compared data regarding the characteristics of children undergoing liver transplantation alone in 2 eras separated by more than a decade from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Transplant recipients from March 1, 2002 to December 31, 2004, compared to those from January 1, 1990, to December 31, 1992, tended to be more evenly distributed across age, race/ethnicity, and disease etiology. There was a major shift toward utilization of partial grafts from both deceased and living donors to achieve transplantation for the youngest children (<1 and 1-5 yr) in particular. However, in spite of these innovative transplant strategies and only a modest increase in demand for pediatric liver transplantation, wait list times for both pediatric candidates and recipients have still increased between eras. In conclusion, the sobering reality that mortality on the waiting list remains highest for the youngest pediatric liver candidates frames our challenge for the next decade.     

Beta-secretase (BACE) and GSK-3 mRNA levels in Alzheimer's disease

Beta-secretase (BACE) and glycogen synthase kinase (GSK 3) are two enzymes thought to play a role in Alzheimer's disease. We extracted mRNA from 90 Alzheimer and 81 control brains. Levels of mRNA were quantified for BACE and GSK 3 with TaqMan real-time RT-PCR. We found no change in the Alzheimer's disease brains relative to controls for either the BACE or the GSK 3alpha mRNA levels.     

Metabolism of acetaminophen by the isolated perfused kidney

Acetaminophen (APAP) produces proximal tubular necrosis in the Fisher 344 rat. This lesion may result from the covalent binding of reactive intermediates of APAP to cellular macromolecules when glutathione (GSH) is sufficiently depleted. Experiments were designed to evaluate the ability of the kidney to convert APAP to reactive electrophilic metabolites capable of depleting renal GSH by quantifying GSH concentrations in isolated perfused kidneys perfused with APAP. Perfusion without APAP reduced (3 X 10(-5) -3 X 10(-5) M) to the perfusion medium further reduced renal GSH content. Treatment of rats with polybrominated biphenyls enhanced the ability of 3 X 10(-8) M APAP to deplete GSH. In contrast, treatment with piperonyl butoxide reduced the depletion of GSH produced by 3 X 10(-5) M APAP. At 3 X 10(-5) M APAP, the glucuronic acid, sulfate and the mercapturic acid conjugates were excreted by the isolate perfused kidneys. After treatment with polybrominated biphenyls, mercapturic acid excretion increased 4-fold, whereas the glucuronic acid and sulfate conjugate excretions were unaffected. These data suggest that the kidney can produce an electrophilic metabolite of APAP which can combine with and deplete renal GSH. An electrophilic metabolite of APAP produced by the kidney may initiate APAP induced renal necrosis.     

Renal tubular transport of paracetamol and its conjugates in the dog.

1 The renal tubular transport of paracetamol and its conjugates was investigated with renal clearance and stop flow studies in the dog. Paracetamol is sparingly bound to plasma proteins and therefore undergoes glomerular filtration. It is reabosrbed in the renal tubules by simple diffusion. 2 The conjugates of paracetamol, the sulphate and the glucuronide, both undergo glomerular filtration being weakly protein bound. At low concentrations in plasma both compounds are secreted by an active transport process. At higher concentrations both compounds are reabsorbed. Clearances are not dependent on urinary pH or flow rate. It is concluded that reabsorption is not a passive process but that there is an active bidirectional transport of the conjugates. 3 Net tubular secretion of the sulphate, but not the glucuronide, conjugate was inhibited by the administration of probenecid.     

How and why politics affect dentistry

Dental practices are under scrutiny every day. The dynamics of the public, the media, the lawmakers, the regulators, and other special-interest groups create endless possibilities for influence over a practice and continue to challenge a dentist's ability to provide quality dental care to patients. This article describes examples of laws and regulations affecting dentistry and the impetus for them, whether real or perceived.     

Malnutrition screening tools: Comparison against two validated nutrition assessment methods in older medical inpatients

ObjectiveAlthough several validated nutritional screening tools have been developed to “triage” inpatients for malnutrition diagnosis and intervention, there continues to be debate in the literature as to which tool/tools clinicians should use in practice. This study compared the accuracy of seven validated screening tools in older medical inpatients against two validated nutritional assessment methods.MethodsThis was a prospective cohort study of medical inpatients at least 65 y old. Malnutrition screening was conducted using seven tools recommended in evidence-based guidelines. Nutritional status was assessed by an accredited practicing dietitian using the Subjective Global Assessment (SGA) and the Mini-Nutritional Assessment (MNA). Energy intake was observed on a single day during first week of hospitalization.ResultsIn this sample of 134 participants (80 ± 8 y old, 50% women), there was fair agreement between the SGA and MNA (κ = 0.53), with MNA identifying more “at-risk” patients and the SGA better identifying existing malnutrition. Most tools were accurate in identifying patients with malnutrition as determined by the SGA, in particular the Malnutrition Screening Tool and the Nutritional Risk Screening 2002. The MNA Short Form was most accurate at identifying nutritional risk according to the MNA. No tool accurately predicted patients with inadequate energy intake in the hospital.ConclusionBecause all tools generally performed well, clinicians should consider choosing a screening tool that best aligns with their chosen nutritional assessment and is easiest to implement in practice. This study confirmed the importance of rescreening and monitoring food intake to allow the early identification and prevention of nutritional decline in patients with a poor intake during hospitalization.     

Glutathione enhances fibroblast collagen contraction and protects keratinocytes from apoptosis in hyperglycaemic culture

BACKGROUND: Cutaneous wound healing is relatively slow in patients with diabetes. OBJECTIVES: To test the hypothesis that this defect in healing of wounds in patients with diabetes results from dysfunction of skin fibroblasts and epidermal keratinocytes and that this dysfunction is related to disrupted intracellular glutathione (GSH) homeostasis. METHODS: We investigated the effects of esterified GSH on the contraction of fibroblasts in a fibroblast-populated collagen lattice and on keratinocyte apoptosis. RESULTS: High glucose medium (hyperglycaemia) reduced the contraction ability of fibroblasts (P < 0.05). The normalization of glucose medium concentrations for hyperglycaemic fibroblasts did not restore the contraction capacity. The percentage of apoptotic keratinocytes was statistically higher in hyperglycaemic cells (P < 0.05). GSH media concentrations ranging from 0.1 to 100 micromol L(-1) restored the ability of hyperglycaemic fibroblasts to contract the gels in a concentration-dependent manner. Primary human keratinocytes grown in hyperglycaemic medium were more susceptible to apoptosis, and treatment with esterified GSH rescued the keratinocytes from apoptosis. CONCLUSIONS: These data suggest that intracellular GSH can normalize skin cell functions disrupted by in vitro cell growth under hyperglycaemic conditions.