Evolution of sleep and sleep EEG after hemispheric stroke

The evolution of subjective sleep and sleep electroencephalogram (EEG) after hemispheric stroke have been rarely studied and the relationship of sleep variables to stroke outcome is essentially unknown. We studied 27 patients with first hemispheric ischaemic stroke and no sleep apnoea in the acute (1-8 days), subacute (9-35 days), and chronic phase (5-24 months) after stroke. Clinical assessment included estimated sleep time per 24 h (EST) and Epworth sleepiness score (ESS) before stroke, as well as EST, ESS and clinical outcome after stroke. Sleep EEG data from stroke patients were compared with data from 11 hospitalized controls and published norms. Changes in EST (>2 h, 38% of patients) and ESS (>3 points, 26%) were frequent but correlated poorly with sleep EEG changes. In the chronic phase no significant differences in sleep EEG between controls and patients were found. High sleep efficiency and low wakefulness after sleep onset in the acute phase were associated with a good long-term outcome. These two sleep EEG variables improved significantly from the acute to the subacute and chronic phase. In conclusion, hemispheric strokes can cause insomnia, hypersomnia or changes in sleep needs but only rarely persisting sleep EEG abnormalities. High sleep EEG continuity in the acute phase of stroke heralds a good clinical outcome.     

Psychosocial Working Conditions Play an Important Role in the Return-to-Work Process After Total Knee and Hip Arthroplasty

Journal of Occupational Rehabilitation - Purpose Both personal and work-related factors affect return to work (RTW) after total knee arthroplasty (TKA) and total hip arthroplasty (THA). Little is...     

Improving medical residents’ self-assessment of their diagnostic accuracy: does feedback help?

Advances in Health Sciences Education - When physicians do not estimate their diagnostic accuracy correctly, i.e. show inaccurate diagnostic calibration, diagnostic errors or overtesting can occur....     

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.     

Gender Variance in Children and Adolescents with Neurodevelopmental and Psychiatric Conditions from Australia

Archives of Sexual Behavior - Gender variance is a broad term used to describe gender non-conforming behaviors. Past studies have used the parental response to Child Behavior Checklist (CBCL) Item...     

Professor Rudolf Marx

Obituary

Professor Rudolf Marx     

Cell-specific coupling of the cloned human 5-HT1F receptor to multiple signal transduction pathways

We recently described the cloning of a fifth member of the 5-hydroxytryptamine (5-HT)₁ (serotonin₁) receptor class that inhibits adenylyl cyclase, namely the human 5-HT_1F receptor (Adham et al. 1993 a). In the present study we have examined in greater detail the functional coupling of the 5-HT_1F receptor in two different cell lines, NIH-3T3 and LM(tk^–) fibroblasts (receptor densities of 1.7 and 4.4 pmol/mg protein, respectively). The maximal inhibitory response elicited by 5-HT was significantly greater in NIH-3T3 as compared to LM(tk^–) cells, whereas the EC₅₀ values were comparable.To investigate the relationship between receptor occupancy and inhibition of cAMP accumulation mediated by 5-HT_1F receptors in NIH-3T3 cells (and hence the degree of receptor reserve), we used the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The half-maximal response required only about 10% receptor occupancy, consistent with a receptor reserve of 90% (88±2.1%, n = 4) for 5-HT-induced inhibition of FSCA. Despite the presence of such a high degree of receptor reserve, a range of intrinsic activities was displayed by structurally diverse classes of compounds. For example, sumatriptan and lysergol were as efficacious as 5-HT itself and thus acted as full agonists, whereas metergoline and 1-NP behaved as partial agonists and as shown previously (Adham et al. 1993a), methiothepin was a silent antagonist (K_b = 438 nM).We have also investigated activation of additional signal transduction pathways by the 5-HT_1F receptor and found that the responses differ in the two cell lines with respect to stimulation of phospholipase C. For example, in NIH-3T3 cells no elevation of inositol phosphates (IP) of [Ca²⁺]_i was observed even at very high agonist concentrations (100 M). In contrast, in LM(tk^–) cells concentrations of 5-HT as low as 10 nM induced stimulation of IP and a rapid increase of [Ca²⁺]i. The 5-HT_1F receptor failed to alter arachidonic acid release in either cell line.The maximal increase in IP accumulation in LM(tk^–) cells was modest, averaging about 100% above basal. The increases of IP and [Ca²⁺]_i required 5-HT concentrations less than one order of magnitude greater than those inhibiting FSCA (EC₅₀ = 17, 55 and 8 nM, respectively), and both responses were blocked by 100 M methiothepin. All three responses (cAMP, IP, and [Ca²⁺]_i) were sensitive to pertussis toxin pre-treatment, suggesting the involvement of G_i/G_o protein(s) in these signal transduction pathways. [Ca²⁺]_i was also elevated by sumatriptan, which may provide a mechanism by which this drug causes constriction of the vasculature. In conclusion, these data indicate that the human 5-HT_1F receptor can couple to multiple effectors, and that this coupling is cell-type dependent.Abbreviations FSCA forskolin-stimulated cAMP accumulation - [Ca²⁺] intracellular free calcium concentration - AA arachidonic acid - EEDQ N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline - CHO chinese hamster ovary cell - LM(tk^–) mouse fibroblast cell - B_max maximal binding site density - K_i apparent dissociation constant obtained from competition binding studies - G protein guanine nucleotide-binding protein - HBS HEPES-buffered saline - IP inositol phosphates - IP₃ inositol 1,4,5 trisphosphate - PLC phospholipase C - K_b antagonist dissociation constant - K_d equilibrium dissociation constant - N-1F-6 stable NIH-3T3 cells expressing the cloned 5-HT_1F receptor - L-1F-3 stable LM(tk^–) cells expressing the cloned 5-HT_1F receptor - PTX pertussis toxin - BSA bovine serum albumin - METH methiothepin - SUMA sumatriptan - 5-MeO-DMT 5-methoxy-N,N-dimethyltryptamine - 1-NP 1-(1-napthyl)piperazine - 5-CT 5-carboxyamidotryptamine Correspondence to: N. Adham at the above address