Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Clinical studies with the potassium channel activator cromakalim in normotensive and hypertensive subjects.

Eight normotensive subjects received single and multiple doses of cromakalim (1 mg) and placebo in a randomised double-blind cross-over study to examine general tolerance to cromakalim and its effects on blood pressure (BP), heart rate (HR), and pressor responses to norepinephrine (NE) and angiotensin II (AII). In a second study, 10 hypertensive patients whose BP control was unsatisfactory with atenolol 50-100 mg received additional treatment with placebo followed by cromakalim 1 mg daily for 4 weeks. Assessments were made of BP, HR, apparent hepatic blood flow and renal blood flow (RBF), pulmonary function, and the pharmacokinetics of atenolol. Cromakalim was generally well tolerated in both normotensive and hypertensive subjects. In the normotensive group, cromakalim produced a reflex increase in HR without any detectable decrease in BP: average (placebo-subtracted) increases in HR at 4 h were 16 beats/min with subjects in an erect position after the single dose and 14 beats/min after 7 days. Cromakalim had no effect on pressor responses to NE and AII. Addition of cromakalim to atenolol was associated with modest further reductions in BP between 0.5 and 3 h after drug administration, with maximal reductions of 21/14 mm Hg (subjects in supine position) 2 h after the first dose. Cromakalim had no effect on apparent liver blood flow and RBF, pulmonary function, and the steady-state pharmacokinetics of atenolol. Single and multiple 1-mg doses of cromakalim are well tolerated but are associated with only modest vasodilator activity.     

Do ethnicity and gender have an impact on pain thresholds in minor dermatologic procedures?

Background and Objectives: The perception of pain is a personal experience influenced by many factors, including genetic, ethnic and cultural issues. Understanding these perceptions is especially important in dermatologic patients undergoing minor surgical operations and who often differ in their pain response to surgical treatments. Little is known about how these differences affect the perception of experimental pain. The purpose of this study was to determine experimental pain perception differences in three distinct East Asian ethnic populations.
Methods: Pain thresholds were examined with a psychophysical computerized quantitative thermal sensory testing device (TSA 2001) in healthy volunteers recruited from three different Asian ethnic groups. Using the methods of limits, experimental pain perception threshold was measured on the forehead and volar aspect of the forearm in 49 healthy subjects. The measurements were then repeated after skin barrier perturbation with adhesive tape stripping of the stratum corneum. All three ethnic groups were analyzed separately with respect to age, gender educational level and skin type.
Results: A total of 20 Chinese, 14 Malay and 15 Indian subjects completed the study. Thermal pain thresholds were similar in all three ethnic groups before and after tape strippings. No significant differences were noted between genders.
Conclusions: Using quantitative sensory thermal testing, we demonstrated that no significant differences in pain occur between different races and genders.     

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.