Effect produced by acute and chronic administration of the selective 5-HT3 receptor antagonist BRL 46470 on the number of spontaneously active midbrain dopamine cells in the rat

This study examined the effect of acute and chronic administration of the selective 5-HT₃ receptor antagonist BRL 46470A, an analog of granisetron, on the number of spontaneously active dopamine (DA) cells in the substantia nigra pars compacta (A9 or SNC) and the ventral tegmental area (A10 or VTA) in the rat. In the A10 area, the acute administration of BRL 46470A decreased the number of spontaneously active DA cells at a dose of 0.1 mg/kg (0.28 μmol/kg) ip, yet increased the number of spontaneously active DA cells at a dose of 0.3 mg/kg (0.84 μmol/kg). The chronic administration (21 days) of BRL 46470A appeared to produce a multiphasic dose-response curve. Thus, the chronic treatment with BRL 46470A increased the number of spontaneously active A10 DA cells at 0.03 (0.084 μmol) and 0.3 mg/kg, but decreased the number of spontaneously active A10 DA cells at a dose of 0.1 mg/kg. In contrast, BRL 46470A did not decrease the number of spontaneously active A9 DA cells after either acute or chronic administration (0.01-0.3 mg/kg). However, BRL 46470A did increase the number of spontaneously active A9 DA cells at acute and chronic doses similar to those that were effective in A10. The iv administration of (+)-apomorphine (APO) not only failed to reverse the decrease produced by chronic administration of BRL 46470A at 0.1 mg/kg, but further decreased the number of spontaneously active A10 DA cells. Similar to the results obtained with granisetron, the pretreatment of naive rats with either 0.01 or 0.1 mg/kg iv of BRL 46470A significantly potentiated (2-fold) the suppressant action of APO on the basal firing rate of A10, but not A9 DA cells. Overall, our results indicate that similar to granisetron, chronic BRL 46470A at 0.1 mg/kg selectively decreases the number of spontaneously active A10 DA cells, via a mechanism not related to depolarization inactivation. Presently, it is not clear what factors may contribute to the multiphasic dose-response curve of BRL 46470A. © 1994 Wiley-Liss, Inc.     

Plasma Lipidome Analysis by Liquid Chromatography-High Resolution Mass Spectrometry and Ion Mobility of Hypertriglyceridemic Patients on Extended-Release Nicotinic Acid: a Pilot Study

Background

Plasma high triacylglycerols and low HDL-C concentration are associated with increased cardiovascular events. Extended-release nicotinic acid (ERN) was shown to reduce plasma triacylglycerols and total cholesterol but also to markedly increase high-density lipoprotein-cholesterol (HDL-C). No data on the effect of ERN on different species of triacylglycerol, cholesteryl ester, and phospholipids are available. In this study, we applied a nontargeted lipidomic approach to investigate the plasma and lipoproteins lipids profile of hypertriglyceridemic patients treated with ERN or a placebo in order to identify new lipids markers associated with this treatment.

Methods

Eight hypertriglyceridemic patients enrolled in a crossover randomized trial with ERN for 8 weeks and treated with 2 g/day of ERN or a placebo. Ultra-performance liquid chromatography (UPLC) coupled to high-resolution mass spectrometry (HRMS) was used in mass spectrometry energy mode (HRMS^E) combined with ion mobility spectrometry to characterize the plasma and very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) lipidome. The accuracy and precision of the method were validated on plasma samples.

Results

Compared to placebo, among 155 plasma lipids characterized using UPLC-ESI-HRMS, a multivariate analysis revealed a significant increase of lysophosphatidylcholine (LPC 20:5), a significant decrease of phosphatidylethanolamine (PE 16:0/22:3) and sphingomyelin (SM d18:1/22:0) and a decrease of triacylglycerol (TG 16:0/16:1/18:2) after ERN treatment. Analysis of these lipids in lipoproteins showed an increase of LPC (20:5) in HDL, a decrease of PE (16:0/22:3) in HDL and LDL, of SM (d18:1/22:0) in VLDL and LDL and of TG (16:0/16:1/18:2) in VLDL.

Conclusion

This lipidomic strategy characterized new specific lipid markers likely to be involved in the effect of ERN on cardiovascular risk opening a new strategy to analyze randomized controlled with this treatment.

Trial Registration

NCT01216956

     

Relative frequencies and sites of presentation of lymphoid neoplasms in a community hospital according to the revised European-American classification

Relative frequencies for common subtypes in the revised European-American classification of lymphoid neoplasms (REAL classification) have been reported. We determined the relative frequencies and sites of presentation of REAL subtypes at a 700-bed community hospital in central Illinois. A database was used to identify and prospectively catalogue all newly diagnosed lymphoid neoplasms from July 1, 1995 to March 1, 1998. The approach to diagnosis and subtyping incorporated morphologic features, immunophenotype, and clinical findings according to criteria proposed in the REAL classification. Of 347 lymphoid neoplasms diagnosed, 319 were subtyped in the REAL classification. Of these, 261 were B-cell neoplasms, 21 were T-cell neoplasms, and 37 were Hodgkin disease variants. Chronic lymphocytic leukemia/small lymphocytic lymphoma/prolymphocytic leukemia, diffuse large cell, and follicle center neoplasms were the most common B-cell subtypes. Large granular lymphocyte leukemia was the most common T-cell neoplasm. Nodular sclerosis was the most common Hodgkin disease variant. The relative frequencies in a US community hospital setting are similar to those reported in other studies. Differences are attributable to patient selection criteria, study group geographic location and racial composition, and/or referral patterns. Diverse REAL classification subtypes may be expected in US community hospitals.     

Cognitive and psychophysiologic response to doxepin and chlordiazepoxide

Seventy-two patients participated in a double-blind evaluation of chlordiazepoxide and doxepin. Levels of anxiety and depression were assessed pre- and posttreatment. Cognitive performance, GSR, EMG, and heart rate were evaluated as functions of the drugs, success-failure set, and motivation. Major results were: (1) For control patients, low depression was associated with high autonomic arousal, and high depression with low arousal; with drug administration, particularly doxepin, these relationships were reversed; (2) Doxepin patients improved on one anxiety and two depression measures as did controls; the chlordiazepoxide group improved on one measure of depression; (3) Doxepin mitigated effects of prior cognitive failure; (4) High-motivation patients who failed manifested decrement in performance; (5) Autonomic activity was higher in the success than in the failure patients with low motivation; opposite effect was shown with high motivation.     

IgE Multiple Myeloma: A Report of the Third Case

The third known case of IgE multiplemyeloma is described. The patient wasa 65-yr-old woman who died 11 moafter a diagnosis of multiple myelomawas made by a surgical biopsy of theleft iliac crest. Her serum containedapproximately 2.7 g/100 ml of a paraprotein of mid- mobility. The isolatedanomalous protein gave a reaction ofidentity with the IgE myeloma proteinof the second reported case when reacted with a specific IgE antiserum.The light-chain type of the myelomaprotein was in contrast to of theother two IgE myeloma proteins. Herclinical manifestations differed fromthe two previously reported cases inseveral respects. She had neitherplasma cell leukemia nor overt BenceJones proteinuria and developed rapidly progressive widespread osteosclerotic lesions that were associated withbone pain.

Submitted on June 7, 1971 Revised on August 9, 1971 Accepted on September 1, 1971     

Rotational constraint in posterior-stabilized total knee prostheses

Rotational stresses from box-post impingement have been implicated in the loosening of posterior-stabilized total knee prostheses. A bench model was constructed to assess the forces generated by tibiofemoral rotation. Rotational torque under load was measured in two different posteriorstabilized total knee prostheses using an axial-torsion load cell at 0 degrees, 20 degrees, and 40 degrees flexion over 20 degrees internal and external rotation. The Sigma posterior-stabilized prosthesis generated little torque through 5 degrees internal and external rotation. An increase in torque then occurred because of box-post impingement, generating peak torques of 17 to 18 N-m at 12 degrees to 14 degrees rotation. The bench model produced the same deformation of the polyethylene post as seen on retrieved specimens. The Scorpio posterior-stabilized prosthesis had a relatively continuous rise in generated torque from tibiofemoral conformity. Box-post impingement did not occur resulting in 32% lower torque between 12 degrees and 14 degrees rotation. Peak rotational torques of 15 to 16 N-m were reached at 19 degrees to 20 degrees rotation. Tibiofemoral conformity is the primary source of rotational constraint. Box-post impingement can be a source of additional rotational constraint. Depending on specific design features, small changes in relative tibiofemoral component rotation can more than double the generated torque. Axial rotation of the knee in vivo can generate substantial torque. Relative tibiofemoral rotational position is an important factor influencing component function and fixation.     

Radiology residency call in the northeastern United States: comparison of difficulty and frequency in programs of different size

RATIONALE AND OBJECTIVES: The purpose of this study was to develop objective measures of residency call frequency and difficulty, to establish mean values for the northeastern United States, and to test those values for correlation with program size. MATERIALS AND METHODS: A survey questionnaire was sent to 104 radiology residency programs in the northeastern United States. The programs were classified according to number of residents, as small (< 11 residents), medium-sized (11-20 residents), large (21-30 residents), or very large (> or = 31 residents). The call difficulty index was defined as the number of emergency examinations per resident per year. Call frequency indexes were defined as the numbers of evenings and of nights during the 4-year residency when residents were scheduled for call. RESULTS: The average call difficulty index and standard deviation for the respondent programs was 3,855 +/- 1,779. The average call frequency index and standard deviation for evenings was 140 +/- 53 and for nights was 120 +/- 59. A significant negative correlation was found between program size on one hand and call difficulty index (r = -0.36, P = .01), evening call frequency index (r = -0.29, P = .033), and night call frequency index (r = -0.51, P < .001) on the other. Residents in small programs could expect to be on call 192 evenings and 192 nights in the 4-year residency and to perform 4,866 emergency examinations per year, as opposed to the 110 evenings and 89 nights on call and the 3,213 emergency examinations that residents in very large programs could expect. In other words, the smaller the program, the more calls residents can expect to take, and the more emergency examinations they will interpret. CONCLUSION: The mean call difficulty and off-hours call frequency indexes established for residency programs of different size in the Northeast demonstrate increasing call difficulty and increasing off-hours call frequency with decreasing program size.