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.     

Abnormal rabbit heterophil chemotaxis following thermal injury. An in vivo model of an abnormality of the chemoattractant receptor for f-met-leu-phe

Previous studies have shown that the decreased neutrophil migratory responsiveness seen in burned patients correlates with the extent of thermal injury and the extent of the neutrophil-specific granule deficiency. To understand better the relationship between the neutrophil dysfunction, degranulation, and thermal injury, a rabbit model was studied. Eighteen rabbits were burned over 20% of their surface area. Assay of peripheral blood heterophils disclosed decreased migratory activity compared with preburn levels and decreased lysozyme content vs preburn levels, but no change in the beta-glucuronidase content. The specific binding of tritiated formyl-methionyl-leucyl-phenylalanine to peripheral blood heterophils was increased fivefold over that of control cells. These studies indicate that, following thermal injury, there is a selective decrease of specific granule contents and an increase in chemoattractant binding to the cell and also suggest an abnormality in chemoattractant receptor processing. The rabbit provides a convenient model for the study of compromised host defenses following thermal injury.     

Lymph node biopsy in patients with human immunodeficiency virus infections

Twenty-one male homosexuals were followed up by repeated lymph node biopsy for a mean (+/- SEM) follow-up of 99 +/- 18 weeks. Four histologic patterns were seen on biopsy: explosive follicular hyperplasia (EFH), follicular involution (FI), a mixed pattern of EFH with FI in the same node, and lymphocyte depletion. Patients with FI and lymphocyte depletion had mean survival times that were significantly less than those for the subjects with EFH. The percentage of lymph node follicles with suppressor cell clusters (T8) in EFH lymph nodes was significantly higher (43% vs 8%) than in nodes from patients without risk for human immunodeficiency virus infection. Helper/suppressor T-cell ratios in control nodes were 1.6; in EFH nodes, 0.97; and in FI nodes, 0.88. A remarkable 33% of patients in this lymphadenopathy group ultimately developed large-cell (B-cell) lymphoma, suggesting that the follicular stimulation noted histologically played a role in the development of this neoplasm. These data show that there is a progressive destruction of lymph node follicles that correlates with the progression of the disease and that lymph node histologic features may provide important prognostic information.     

The HemoCue®, a point of care B-hemoglobin photometer, measures hemoglobin concentrations accurately when mixedin vitro with canine plasma and three hemoglobin-based oxygen carriers (HBOC)

PURPOSE: Accuracy of measurement of low hemoglobin concentrations using the HemoCue, a B-hemoglobin photometer (HemoCue AB, Angelholm, Sweden) may exhibit significant variability. Infusion of hemoglobin-based oxygen carriers (HBOC) results in low concentrations of plasma hemoglobin. Our study assessed B-hemoglobin photometer measurement accuracy of three HBOC: (hemoglobin glutamer-200 (bovine; Oxyglobin, Biopure Corp., Cambridge, MA, USA); hemoglobin glutamer-250 (bovine; Hemopure, Biopure Corp, Cambridge, MA, USA), and hemoglobin-raffimer, (human; Hemolink, Hemosol, Inc., Toronto, Ontario, Canada). METHODS: In the laboratory, 45 split canine plasma samples were mixed with hemoglobin glutamer-200 (8.13, 16.25, 32.5 g x L(-1) concentrations), 45 samples were mixed with hemoglobin glutamer-250 (8.13, 16.25, 32.5 g x L(-1) concentrations), 45 with hemoglobin-raffimer (12.5, 25.0, 50.0 g x L(-1) concentrations), and measured. Plasma samples without HBOC served as control. Hemoglobin concentration was determined by a laboratory analyzer (Coulter Corporation, Hiafeah, FL, USA) and B-hemoglobin photometer (HemoCue, Angelholm, Sweden). Two independent technicians performed blinded sample measurements and randomly tested each sample five times. Results were analyzed according to Bland and Altman analysis. RESULTS: B-hemoglobin photometer demonstrated high repeatability for all three HBOCs. Repeatability coefficients were 0.37 g x L(-1) and 0.48 g x L(-1) for hemoglobin glutamer-200, 0.39 g x L(-1) and 0.4 g x L(-1) for hemoglobin glutamer-250 and 1.07 g x L(-1) and 0.85 g x L(-1) for hemoglobin-raffimer. An acceptable agreement was found between the B-hemoglobin photometer and the laboratory analyzer for all three HBOCs tested. CONCLUSION: The B-hemoglobin photometer accurately determined the concentration of three HBOC solutions dissolved in canine plasma.     

Analysis of lick rate measures the positive and negative feedback effects of carbohydrates on eating

Previous work has shown that measuring the rate of ingestion of liquid diets, rather than simply volume, reveals important features of ingestive behavior which can help to explain why a particular volume of a liquid is ingested. This study is an extension of that work to a variety of different test solutions. In this study the rate of ingestion of saccharin, two different concentrations of glucose and sucrose and their mixtures with saccharin and seven different concentrations of maltose were measured. The rate functions were fit by the least-squares method to a linear function to determine the intercepts and slope constants. Analysis of how these two parameters changed with the concentration and composition of the test solutions confirms, using different test solutions, a previously reported conclusion that the initial rate of ingestion (the intercept) measures palatability and that the slope constant is a measure of the rate of development of a negative feedback satiety signal.     

Effect of dietary restriction upon the age-associated decline of lymphocyte DNA repair activity in mice

Effects of dietary restriction (DR) on DNA repair capacity of mouse splenocytes after ultraviolet (UV)-induced damage were assessed. Two mouse cohorts received restricted amounts of purified hypocaloric diets; one was minimally restricted (∼75% of the caloric intake of mice fed a commercial diet ad libitum), the other was severely restricted (∼50% caloric restriction). An inverse correlation between age and DNA repair was present in the two cohorts; however, the regression lines of the two cohorts showed different slopes. DR appears to decelerate the age-associated decline of DNA repair capacity, and this delay might account in part for the improved immune function shown by old mice on DR.     

Characteristics of Hidden Status Among Users of Crack, Powder Cocaine, and Heroin in Central Harlem

This article analyzes hidden status among crack, powder cocaine, and heroin users and setters, in contrast to more accessible users/sellers. Several sampling strategies acquired 657 users (N=559) and sellers (N=98). Indicators of hidden status were those who (1) paid rent in full in the last 30 days, (2) used nonstreet drug procurement. (3) had legal jobs, and (4) earned $1,000 or more in legal income in the last 30 days. Nearly half had at least one indicator: approximately 16% of users/sellers had two to four indicators. In logistic regression analyses, those who had not panhandled in the last 30 days, those who had used powder cocaine in the last 30 days, and those never arrested were the most likely to have hidden status, whether the analysis predicted those having any indicators or those having two to four indicators. The four indicators begin to operationally define hidden status among users of cocaine and heroin.     

Activity-induced weakness in recessive myotonia congenita with a novel (696+1G>A) mutation.

OBJECTIVE: To investigate the cause of the transient weakness that occurs in recessive myotonia congenita (RMC) following sustained muscle contraction. METHODS: Nerve excitability studies were performed on a 35-year-old male with RMC due to a novel 696+1G>A CLCN1 mutation. The median nerve was stimulated at the wrist and compound muscle action potentials (CMAPs) were recorded from abductor pollicis brevis (APB). Stimulus-response behaviour using two stimulus durations, threshold electrotonus to 100-ms polarizing currents, a current threshold relationship and the recovery of excitability following supramaximal stimulation were recorded at rest. Excitability parameters were also recorded before and after maximal voluntary contraction (MVC) of APB against resistance for 60s. Results were compared to data obtained from 12 normal controls. RESULTS: Baseline axonal excitability parameters were all normal, indicating that axonal function was normal at the point of stimulation. Following one minute of MVC, excitability parameters demonstrated a significant increase in threshold when compared to controls (RMC 54.9%; controls 15.5+/-3.1%). In the RMC patient, this increase in threshold was associated with a 39% reduction in the amplitude of the maximal CMAP, which remained unaffected in controls. CONCLUSIONS: The reduction in maximal CMAP is likely to represent muscle activation failure due to depolarization block, with the increase in threshold possibly reflecting a compensatory attempt by motor axons to overcome prolonged contraction-induced changes in the muscle membrane. SIGNIFICANCE: The prolonged recovery of excitability following sustained muscle contraction is likely to be a contributing factor to symptoms of weakness and fatigue experienced by RMC patients.