Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.     

A quick, sensitive high-performance liquid chromatography assay for monoethylglycinexylidide and lignocaine in serum/plasma using solid-phase extraction.

Recent advances in the investigation of liver disease and transplantation have seen the introduction of lignocaine as a probe of liver function. For this purpose, an assay that is sensitive and rapid is required for the major metabolite of lignocaine, monoethylglycinexylidide (MEGX). We have developed an accurate, low-cost high-performance liquid chromatography (HPLC) method using Bond-Elut phenyl (1 cc) cartridges for sample preparation. The total preparation time for five samples is less than 10 min and the run time is approximately 10 min/sample. Each cartridge can be used at least four times. Simultaneous measurement of another metabolite of lignocaine, glycinexylidide (GX), can be achieved by adjustment of the mobile phase and flow rate. The chromatogram is monitored with an UV detector at 210 nm. The inter- and intra-assay coefficients of variation for MEGX (10-250 micrograms/L) and lignocaine (100-2,000 micrograms/L) are less than 9.5 and less than 2%, respectively, with recoveries for MEGX, trimethoprim (internal standard), and lignocaine all greater than 85%. This method offers a rapid, sensitive assay that is clinically useful in the new role for lignocaine/MEGX in dynamic liver function testing.     

The abnormal anatomy of cleft lip and its correction

Summary The importance of the premaxillary position, size and shape in the development of the face and nose is discussed. The anthropological development of the premaxilla is studied. These factors are to be considered when cleft lip repairs are being planned and developed. Several cases are presented and discussed.     

Pharmacogenetic screening and therapeutic drugs.

BACKGROUND: Pharmacogenetics is the science of the influence of heredity on pharmacological response. ISSUES: The cost of severe adverse drug reactions in individuals has been estimated in the US alone to be in excess of US$4 billion. It has been argued that in a significant proportion of cases, the efficacy and toxicity profiles of drug therapy would be substantially improved in individuals if characteristics due to genetic variation were taken into account. Methods are now available, which make screening for susceptibility feasible. CONCLUSIONS: There are several therapeutic areas in which screening may give rise to significant improvements in outcome with cost-benefits to both the individual and the community. However, there is currently a lack of data on which cost-benefit analysis can be based. The challenge is to provide this information for new drugs, and for drugs with established therapeutic roles.     

Serotonin-binding proteins in the bovine cerebral cortex: interaction with serotonin and catecholamines.

The soluble serotonin-binding proteins (SBP) present in bovine frontal cortex are very similar to those reported in rat brain. Binding of [3H]serotonin to SBP, present in ammonium sulphate-precipitated proteins from bovine cortex, requires Fe2+ but not Fe3+. In the presence of an optimal concentration of Fe2+ (0.1 mM), bovine SBP behave as a single class of non-cooperative sites for [3H]serotonin binding (Bmax = 120 +/- 12 pmol/mg protein, KD = 0.12 +/- 0.04 microM, n = 3). Binding of [3H]serotonin is decreased by nucleotides and by reagents which modify sulfhydryl groups and reduce disulfide bonds and by metal ion chelators. Serotonin analogs possessing an hydroxyl group on the indole ring and catecholamine analogs possessing an intact catechol moiety are effective competitors (Ki from 0.1 to 0.3 microM). In both cases, the aliphatic amino group does not contribute to the binding, but the affinity is strongly decreased if aromatic hydroxyl groups are methoxylated. Catecholamine-SBP interactions can also be demonstrated directly by binding experiments. Binding of [3H]dopamine is greatly enhanced by Fe2+, Cu2+ and Mn2+, but not by Fe3+. The Fe(2+)-dependent binding component of [3H]dopamine is saturable (Bmax = 279 +/- 64 pmol/mg protein, KD = 0.19 +/- 0.02 microM, n = 3), and possesses the same physicochemical properties as SBP: it elutes immediately after the void volume on a Sephacryl S100 HR (1.6 x 140 cm) gel filtration column (reflecting aggregation) and it migrates with an apparent molecular weight of 57-58 kDa on native polyacrylamide gel electrophoresis. Whereas the serotonin-storing role of SBP in serotonergic neurons has already been well documented, the present data advocate that these proteins may also possess catecholamine-storing properties.