Olanzapine versus risperidone in the treatment of post-psychotic depression in schizophrenic patients

OBJECTIVE: To compare the efficacy of two atypical antipsychotic drugs, olanzapine and risperidone, in schizophrenic patients with post-psychotic depression. RESULTS: A clinically significant decrease of MADRS scores occurred in patients treated with both drugs for 8 weeks. CONCLUSION: Atypical antipsychotic drugs may be particularly appropriate when treating schizophrenic patients with depression.     

Losartan reduces the costs associated with nephropathy and end-stage renal disease from type 2 diabetes: Economic evaluation of the RENAAL study from a Canadian perspective

BACKGROUND: The Reduction of Endpoints in NIDDM [non-insulin-dependent diabetes mellitus] with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated the renoprotective effects of losartan in patients with nephropathy from type 2 diabetes. OBJECTIVE: To perform an economic evaluation of the costs associated with end-stage renal disease (ESRD) from a Canadian public health perspective, based on the clinical outcomes reported in the RENAAL study. METHODS: ESRD-related costs were determined by estimating the mean number of days with ESRD multiplied by the daily cost of ESRD (140 dollars); mean days with ESRD were calculated by subtracting the area under the Kaplan-Meier survival curve for time to the first event of ESRD or all-cause mortality from the area under the curve for all-cause mortality. Daily ESRD cost was determined using Canadian specific data sources. ESRD-related cost savings with losartan were obtained by subtracting the ESRD-related costs of the losartan group from those of the placebo group. Net cost savings were ESRD-related cost savings with losartan minus the drug cost of losartan. RESULTS: Losartan reduced the number of ESRD days by 33.6 per patient over 3.5 years (95% CI 10.9 to 56.3) compared with placebo. Losartan reduced ESRD-related costs by 4,695 dollars per randomized patient over 3.5 years (95% CI 1,523 dollars to 7,868 dollars). After accounting for the drug cost of losartan, net cost savings with losartan were 3,675 dollars per randomized patient over 3.5 years. CONCLUSION: Losartan therapy for patients with nephropathy from type 2 diabetes reduces the clinical incidence of ESRD and can result in considerable cost savings for the Canadian public health system.     

Agonist- and antagonist-induced sequestration/internalization of neuropeptide Y Y1 receptors in HEK293 cells

1 Neuropeptide Y Y(1) receptors are known to internalize following the binding of agonists. In the present study, a pseudopeptide Y(1) receptor antagonist, homodimeric Ile-Glu-Pro-Dpr-Tyr-Arg-Leu-Arg-Tyr-CONH(2) (GR231118), also induced Y(1) receptor internalization in human embryonic kidney (HEK293) cells. 2 We demonstrated first that both specifically bound radiolabeled antagonist ([(125)I]GR231118) and agonist ([(125)I][Leu(31), Pro(34)]PYY) underwent receptor-mediated sequestration/internalization in transfected HEK293 cells. 3 Agonist-induced Y(1) receptor internalization was dependent on clathrin-coated pits and was regulated in part by Gi/o-protein activation as revealed by pertussin toxin sensitivity. In contrast, antagonist-induced sequestration of Y(1) receptors was partly dependent on clathrin-coated pits, but independent from Gi/o-protein activation. 4 Exposure to high concentrations of agonist or antagonist caused a 50 and 75% loss of cell surface binding, respectively. The loss caused by the agonist rapidly recovered. This phenomenon was blocked by monensin, an inhibitor of endosome acidification, suggesting that cell surface receptor recovery is due to recycling. In contrast to the agonist, GR231118 induced a long-lasting sequestration of Y(1) receptors in HEK293 cells. 5 Immunofluorescence labeling indicated that following 40 min of incubation with either the agonist or the antagonist, Y(1) receptors followed markedly different intercellular trafficking pathways. 6 Taken together, these findings provided evidence that a pseudopeptide Y(1) receptor antagonist can induce long-lasting disappearance of cell surface receptors through a pathway distinct from the classical endocytic/recycling pathway followed by stimulation with an agonist.     

Adrenomedullin receptor binding sites in rat brain and peripheral tissues

The existence of specific adrenomedullin receptor binding sites was investigated using the agonist peptide fragment [125I]human adrenomedullin-(13-52) in rat brain, lung and vas deferens homogenates. Saturation-binding experiments suggest that [125I]human adrenomedullin-(13-52) binds to an apparent single population of sites with similar affinities (K(D) of 0.3 to 0.6 nM) but with different maximal binding capacity in the rat brain, lung and vas deferens homogenates (B(max) of 73, 1760 and 144 fmol/mg protein, respectively). Competition-binding experiments using various analogues and fragments of calcitonin gene-related peptide (CGRP) and adrenomedullin were also performed using this radioligand. Competition-binding profiles suggest the possible existence of heterogeneous populations of adrenomedullin receptor binding sites. For example, in rat brain, human adrenomedullin-(1-52) and human adrenomedullin-(13-52) competed against specific [125I]human adrenomedullin-(13-52) sites with competition curves best fitted to a two-site model. Additionally, human calcitonin gene-related peptide alpha (hCGRPalpha), [Cys(Et)(2,7)]hCGRPalpha and [[R-(R,(R*,S*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-Piperidinecarboxamide] (BIBN4096BS) competed against specific [125I]human adrenomedullin-(13-52) binding with profiles that were also best fitted to a two-site model. Furthermore, binding assays performed in the presence of GTPgammaS (100 microM) revealed that this compound inhibited 20% of specific [125I]human adrenomedullin-(13-52) sites in rat brain homogenates and competition curves of human adrenomedullin-(1-52) and [Cys(Et)(2,7)]hCGRPalpha against specific [125I]human adrenomedullin-(13-52) sites remained best fitted to a two-site model. Moreover, the existence of specific [125I]human adrenomedullin-(13-52) binding sites that are resistant to human adrenomedullin-(22-52) and human CGRP-(8-37) is suggested in the rat brain and vas deferens. Taken together, these data provide evidence for the possible existence of heterogeneous populations of adrenomedullin binding sites in rat brain and peripheral tissues.     

Child abuse study among Swedish physicians and medical students

Background: The purpose of the present paper was to examine the attitudes and experiences of reporting child abuse and neglect among primary care and hospital‐based physicians and to study the responses of physicians and medical students to case vignettes suggestive of possible physical abuse or neglect. Methods: Physicians at the child health centers in Göteborg primary care (n= 44) and the general pediatricians at the pediatric hospital (n= 21) in Göteborg answered a questionnaire regarding their attitude and experiences reporting child abuse and neglect. The physicians and medical students (n= 34) responded to three case vignettes in which child abuse and neglect could be suspected. Results: A majority of the physicians had reported child abuse and neglect to the social services (80%). No differences were found between primary care and hospital‐based physicians in terms of reporting or attitudes. Two‐thirds of the physicians had suspected child abuse and neglect and decided not to report, and the major reason for not reporting was a lack of confidence in social services organization. Twenty‐one percent had never reported a child for abuse or neglect during their working career. Medical students were more likely to report hypothetical cases than physicians. Conclusion: Many physicians have reported child abuse to social services but also have neglected to do so even when suspecting abuse. It is important that medical students’ willingness to report is continued when starting to work clinically and that all physicians should be continuously educated.