Liver transplant and hepatitis C in methadone maintenance therapy: a case report

Methadone maintenance therapy for the treatment of opioid dependence continues to carry a social stigma. Until recently, patients on methadone were not considered for liver transplantation. We describe the first case of a patient on methadone who received a liver transplant for end stage liver disease and was successfully treated for recurrent hepatitis C. More than five years post transplant and three years post viral clearance, the patient continues to do well and is stable on low-dose methadone. This case emphasizes the need to reconsider the non-evidence based policy adopted by transplant centers that require methadone maintenance therapy patients to stop methadone prior to consideration for transplant evaluation.     

Glutathione trapping to measure microsomal oxidation of furan to cis-2-butene-1,4-dial.

Furan is a liver carcinogen and toxicant. Furan is oxidized to the reactive dialdehyde, cis-2-butene-1,4-dial, by microsomal enzymes. This reactive metabolite readily reacts with glutathione nonenzymatically to form conjugates. A high-performance liquid chromatography-electrochemical method for the detection of cis-2-butene-1,4-dial-glutathione (GSH) conjugates in microsomal preparations was developed to measure the extent of furan metabolism to cis-2-butene-1,4-dial in vitro. Previously unobserved mono-GSH reaction products of cis-2-butene-1,4-dial were detected in addition to the already characterized bis-GSH conjugates. Chemical characterization of these compounds indicated that the alpha-amino group of glutathione had reacted with cis-2-butene-1,4-dial to form a thiol-substituted pyrrole adduct. The analytical method was used to estimate the extent of furan oxidation in rat liver microsomes from untreated or acetone-pretreated F344 rats as well as in human P450 2E1 Supersomes. Our results confirm that cytochrome P450 2E1 can catalyze the oxidation of furan to cis-2-butene-1,4-dial. However, the data are also consistent with the involvement of other P450 enzymes in the oxidation of furan in untreated animals. This assay will be a valuable tool to explore tissue and species differences in rates of furan oxidation.     

Intracerebroventricular LHRH relieves behavioral deficits due to vomeronasal organ removal

Contact between the sexes in many species is known to produce hormonal changes in the male [increases in serum luteinizing hormone (LH) and/or testosterone] that can be interpreted as due to an intracerebral release of LH-releasing hormone (LHRH). In some circumstances, these hormonal changes appear to depend on an intact vomeronasal sensory system. Exogenous LHRH is also known to facilitate mating behavior in several species. We show here that LHRH delivered into the cerebral ventricles can restore some mating behavior lost when the vomeronasal organs are removed from sexually inexperienced male hamsters. The results are consistent with our working hypothesis that intracerebral LHRH release is an intermediate in the facilitation of mating behavior by vomeronasal sensory input.     

Sampling Patients Within and Across Health Care Providers: Multi-Stage Non-Nested Samples in Health Services Research

In order to better inform study design decisions when sampling patients within and across health care providers we develop a simulation-based approach for designing complex multi-stage samples. The approach explores the tradeoff between competing design goals such as precision of estimates, coverage of the target population and cost.We elicit a number of sensible candidate designs, evaluate these designs with respect to multiple sampling goals, investigate their tradeoffs, and identify the design that is the best compromise among all goals. This approach recognizes that, in the practice of sampling, precision of the estimates is not the only important goal, and that there are tradeoffs with coverage and cost that should be explicitly considered. One can easily add other goals. We construct a sample frame with all phase III clinical cancer treatment trials that are conducted by cooperative oncology groups of the National Cancer Institute from October 1, 1998 through December 31, 1999. Simulation results for our study suggest sampling a different number of trials and institutions than initially considered.Simulations of different study designs can uncover efficiency gains both in terms of improved precision of the estimates and in terms of improved coverage of the target population. Simulations enable us to explore the tradeoffs between competing sampling goals and to quantify these efficiency gains. This is true even for complex designs where the stages are not strictly nested in one another.     

Dose fractionation of radiolabeled antibodies in patients with metastatic colon cancer.

Twelve patients with metastatic colon cancer were treated with 131I-chimeric B72.3 (IgG-4) at total doses of 28 or 36 mCi/m2 in two or three weekly fractions. Bone marrow suppression was the only significant side effect. The degree of bone marrow suppression adjusted for whole-body dose was modestly but statistically significantly (p = 0.04) less than that seen with identical doses given as a single infusion for the total dose of 36 mCi/m2. Nine of twelve patients developed an antibody response to ch B72.3, which altered the kinetics of radiolabeled antibody in four patients given a second course of therapy. One patient had a minor response that lasted 4 mo. Fractionation of this particular radiolabeled antibody at the dose schedule used produced a modest increase in the therapeutic window in regard to administered dose.     

Muscle glycogen and glucose uptake during exercise in humans.

Six men were studied during 40 min of cycling exercise to examine the relationship between leg glucose uptake and muscle glycogen concentration. Exercise resulted in significant increases in leg glucose uptake, while muscle glycogen and arterial blood glucose concentrations declined. Arterial plasma insulin levels did not change significantly. There was a significant inverse relationship between muscle glycogen concentration and glucose uptake during exercise which suggests a possible regulatory influence of muscle glycogen on glucose uptake in the early stages of exercise in humans.     

Family dynamics and emotional expression among patients with chronic pain and depression

Exploration of the relative roles of family dynamics and release of constrained, negative emotion in changing pain and depressive symptoms. Eighteen patients presenting mild to moderate depression and diagnoses of psychogenic pain disorder were randomly assigned to 1 of 2 treatment groups. One group was designed to facilitate the release of constrained and overcontrolled negative affect while the other was designed to provide information about pain and depression. Findings suggest that initial incongruity between patient's and significant other's ratings of family relationships retard changes in pain status and depressive symptoms. No significant differences were noted between patients who were taught to express negative feelings and those who were taught simply to understand those feelings. Results are discussed in terms of theories about family dynamics in the initiation and maintenance of pain conditions and in terms of the role of constrained affect as a precursor to both psychogenic pain and depression.