Search

Originally, a role for sleep in learning and memory has been advocated following the observation of sleep-dependent performance enhancements at simple procedural tasks. With the investigation of a variety of cognitive and behavioral abilities, multiple stages of memory were further suggested to benefit from the off-line reprocessing believed to occur during specific sleep stages. In particular, REM sleep has been implicated in the integration of new information into associative networks as well as in the abstraction and generalization of implicit rules allowing adaptive behaviors. In a recent study, we extended these observations by demonstrating that the mediating effect of expectation on placebo-induced analgesia is strengthened by sleep, and that the individual amount of REM sleep is predictive of the relief expected on the next morning. However, this relation is strongly modulated by the level of concordance between expectations and sensory information available prior to sleep. As placebo responses derive from the learned association between contextual cues and subsequent relief, these results are discussed in relation to the proposed roles of REM sleep in the integrative stages of memory processing. In light of the responsiveness of REM sleep to waking events, its expression is also proposed to reflect the cognitive demand associated with the offline reprocessing of information necessary for the assimilation of new expectations to one's belief system.

Objective: Both short and long sleep duration have frequently been found to be associated with an increased risk for diabetes. The aim of the present exploratory analysis was to examine the association between sleep duration and type 2 diabetes after lifestyle intervention in overweight individuals with impaired glucose tolerance in a 7-year prospective follow-up., Research Design and Methods: A total of 522 individuals (aged 40-64 years) were randomly allocated either to an intensive diet-exercise counseling group or to a control group. Diabetes incidence during follow-up was calculated according to sleep duration at baseline. Sleep duration was obtained for a 24-h period. Physical activity, dietary intakes, body weight, and immune mediators (C-reactive protein and interleukin-6) were measured., Results: Interaction between sleep duration and treatment group was statistically significant (P = 0.003). In the control group, the adjusted hazard ratios (HRs) (95% CI) for diabetes were 2.29 (1.38-3.80) and 2.74 (1.67-4.50) in the sleep duration groups 9-9.5 h and >or=10 h, respectively, compared with for that of the 7-8.5 h group. In contrast, sleep duration did not influence the incidence of diabetes in the intervention group; for sleep duration groups 9-9.5 h and >or=10 h, the adjusted HRs (95% CI) were 1.10 (0.60-2.01) and 0.73 (0.34-1.56), respectively, compared with that in the reference group (7-8.5 h sleep). Lifestyle intervention resulted in similar improvement in body weight, insulin sensitivity, and immune mediator levels regardless of sleep duration., Conclusions: Long sleep duration is associated with increased type 2 diabetes risk. Lifestyle intervention with the aim of weight reduction, healthy diet, and increased physical activity may ameliorate some of this excess risk.

The development of anti-factor VIII (FVIII) antibodies (Abs), also called inhibitors, is currently one of the most serious complications arising during the treatment of hemophilia A patients. Improved prevention and eradication of these Abs remain a challenge both for clinicians and scientists. Numerous studies in the literature have reported on their epitope specificity, on their mechanism of FVIII inactivation, as well as on the methods used for their detection. In this review, we summarize the current knowledge on the nature (isotypes, kinetic properties), epitope properties, and mechanisms of action of anti-FVIII Abs. Furthermore, we present methods for detection and epitope characterization of anti-FVIII Abs with emphasis on the Luminex technique susceptible to facilitate the monitoring of changes in the epitope specificity of these Abs.

The experience of a sensory event is extensively shaped by past experience and expectations. Placebo analgesia, one of the most studied models of expectation-mediated effects, can be induced by suggestion of analgesia and conditioning. The present study examined the possibility that sleep might contribute to the consolidation of new expectations and consequently influence the generation of expectation-mediated placebo effects. Strong expectations of analgesia were generated before sleep by conditioning manipulations wherein the intensity of thermal pain stimulation was surreptitiously reduced after the application of a topical placebo cream. Expectations and placebo analgesic effects were measured the following morning and compared with those of a control daytime group without sleep. Although placebo effects were observed in both groups, correlation analysis suggests that the mediating effect of expectations on placebo responses was strongest in the overnight group. Moreover, after exposure to a convincing analgesia experience, the relative duration of rapid eye movement (REM) sleep decreased in subjects showing higher analgesic expectations and placebo responses the next morning. In a third group exposed to less consistent analgesic experiences before sleep, expectations reported in the morning were comparable with other groups. However, expectations were positively correlated with REM sleep and did not emerge as a significant mediator of the analgesic effect. Together, these findings show that sleep-related processes may influence the association between expectations and placebo analgesia and that REM sleep can predict placebo-induced expectations of pain relief. However, equivocal previous experience with treatments may significantly alter the relationship between relief expectation, REM sleep, and placebo effects.

The 4-hydroxyimidazolium salt, readily prepared in two steps by acylation of a formamidine and quaternization of the second nitrogen, affords, after deprotonation, the anionic imidazol-2-ylidene-4-olate, which can be complexed to a transition metal and still be subsequently functionalized at O or C backbone atom in the outer coordination sphere of the metal.

Background: Sleep complaints (e.g., frequent awakenings, nightmares), headaches and mood alterations (e.g., feeling depressed, irritable) can appear following a mild traumatic brain injury (MTBI). The objective of this retrospective study was to assess the relationships between the above symptoms. Our hypothesis was that sleep complaints might be among the risk factors for the development of headaches and mood alterations., Methods: The consecutive charts of 443 patients (68.2% males vs. 31.8% female; mean age of 46.9 years) diagnosed with MTBI were reviewed for past medical history and above symptoms using the Rivermead post-concussion symptom assessment questionnaire and self-report. Data were retrieved in 2 time courses: 10 days and 6 weeks., Results: For the 2 time courses, the prevalence of subjective sleep complaints were 13.3% and 33.5%; headaches 46.8% and 39.3%; feeling depressed 9.5% and 20.4%; and feeling irritable 5.6% and 20.2%, respectively. Reports of sleep complaints at 6 weeks were 2.9 times (p=0.004) more likely if such a symptom was reported at 10 days. Moreover, the presence of sleep complaints at 10 days is associated with concomitant headaches, depressive symptoms, and feeling irritable by 2.3, 9.9, and 12.2 times (p=0.0001 and 0.014); and by 2.9, 6.3, and 4.8 times (p=0.0001) at 6 weeks, respectively., Conclusions: Our results suggest that patients afflicted with sleep complaints are more likely to suffer from concomitant headaches, depressive symptoms, and irritability.

This study was designed to estimate the validity of an 11-point verbal numerical rating scale (VNRS) and a 100 Unit (U) plasticized visual analogue scale (VASp) using a 100mm paper visual analogue scale (VAS) as a gold standard, to recommend the best method of reporting the intensity of acute pain in an emergency department (ED). A convenience sample of 1176 patients with acute pain were recruited in the ED of a teaching hospital. Patients >18 years and able to use the different scales were included. Scales were presented randomly. Results were converted to a 0-100 U scale and validity was quantified using the Bland-Altman method and the intra-class correlation (ICC). The limits of acceptability were previously set for the limits of agreement at +/-20 U, with a constant bias. The Bland-Altman method revealed a small bias of -4 U for the VNRS and +1 U for VASp. However, the bias of the VNRS varied with the intensity of pain from -10 to +1 U. The limits of agreement between the VNRS&VAS and the VASp&VAS were -25; +17 U and -17; +18 U, respectively. The ICC was excellent between the VNRS&VAS (0.88) and the VASp&VAS (0.92). In conclusion, the VASp has a small bias, acceptable limits of agreement and an excellent intra-class correlation. It is probably a valid tool to estimate acute pain in the ED. However, the VNRS is less valid in that context because of its wide limits of agreement and variable bias (mainly in lower scores).

Pyrimidinium betaïnes (1), readily accessible via a straightforward modular synthesis from a formamidine and a monosubstituted malonic acid, are readily deprotonated by nBuLi (or KHMDS) to give the stable carbene species [2]Li+ (abbreviated as maloNHC). The latter represents the archetype of a subgroup of N-heterocyclic carbenes incorporating a malonate as remote anionic functional group within their heterocyclic backbone. While playing the dual role of monodentate 2 e- L type donor and noncoordinating charge carrier X, such ligands are seen to provide a rational route to zwitterionic complexes, as illustrated here by three examples (Rh, Fe, Ag). In particular, the reaction of [2]Li+ with [RhCl(1,5-COD)]2 produces the neutral 14 e- complex Rh(maloNHC)(COD) (3) in which coordinative unsaturation at the metal is relieved in the solid state by an uncommon labile bonding interaction between the Cipso of one of the mesityl arms and the Rh center.

The development of antibodies (Abs) against infused factor VIII (FVIII) is currently one of the most serious complications in the treatment of patients suffering from haemophilia A. Improved prevention and eradication of these anti-FVIII Abs remain a challenge for both clinicians and scientists. Here we describe an immunoassay to simultaneously detect and map the epitope specificity of haemophilia A patients' inhibitors by screening plasma against both heavy and light chains (HC and LC) of human plasma-derived FVIII (pFVIII). The format used was a two-site sandwich assay, where one monoclonal antibody (mAb) specific for the HC or LC was first immobilized on beads, and then incubated with the different forms of pFVIII. After incubation with patients' plasma samples, binding was revealed by a phycoerythrin-labeled secondary Ab. Samples from haemophilia patients with autoantibodies (autoAb) or alloantibodies (alloAb) were screened in this format. The former preferentially recognized the LC, whereas the latter were directed against both LC and HC. This technology appears attractive as it is fast and requires only 100 microl of patient's plasma. Furthermore, not only are anti-FVIII Abs detected, but information on their epitopic specificity is also obtained.

Background and Objectives: Sleep affects the control of circulation and respiratory function. Gender and age are also known to have a profound impact on the neural control of circulation. We investigated whether gender affects sleep-related cardiovascular and respiratory responses and whether these vary according to healthy subjects being young or middle-aged., Methods: We studied 32 subjects: 8 women and 8 men aged 20-30 years (young), and 8 women and 8 men aged 50-60 years (middle-aged). Young women were under oral contraceptive therapy and middle-aged women were postmenopausal and not receiving hormonal replacement therapy. One-night polysomnography was used to assess RR variability during non-rapid eye movement (NREM) (stage 2) and rapid eye movement (REM) sleep. Low-frequency (LF) and high-frequency (HF) components, in normalized units (LFnu and HFnu) and LF/HF ratio were calculated on five-minute segments selected across the night and averaged for each sleep stage. The respiration frequency in NREM and REM sleep was also measured. Interaction between gender, age and sleep on autonomic and respiration variables was assessed by 2 x 2 x 2 analysis of variance (ANOVA)., Results: Compared to men, women had a greater NREM-to-REM increment in LFnu (gender-by-state interaction, p<0.01), a greater decrement in HFnu (interaction, p<0.01) and a greater increment in LF/HF (interaction, p<0.05). Women also showed a more pronounced increase in respiratory frequency during REM sleep compared to men in both groups of age (gender-by-state interaction, F=7.1, p<0.05). No gender-by-age-by-state interaction was observed to affect autonomic and respiration variables., Conclusion: NREM-to-REM excitatory cardiac and respiratory responses are more marked among women compared to men, regardless of their hormonal status and whether they are young or middle-aged.

The objectives of the study were to measure the prevalence of periodic leg movements during NREM and REM sleep (PLMS) and while awake (PLMW) and to assess the impact of PLMS on nocturnal sleep and daytime functioning in patients with narcolepsy. One hundred and sixty-nine patients with narcolepsy and 116 normal controls matched for age and gender were included. Narcoleptics with high and low PLMS indices were compared to assess the impact of PLMS on sleep and Multiple Sleep Latency Test (MSLT) variables. More narcoleptics than controls had a PLMS index greater than 5 per hour of sleep (67% versus 37%) and an index greater than 10 (53% versus 21%). PLMS indices were higher both in NREM and REM sleep in narcoleptic patients, but the between-group difference was greater for REM sleep. A significant increase of PLMS index was also found with aging in both narcoleptic patients and controls. PLMW indices were also significantly higher in narcoleptic patients. Patients with an elevated index of PLMS had a higher percentage of stage 1 sleep, a lower percentage of REM sleep, a lower REM efficiency and a shorter MSLT latency. The present study demonstrates a high frequency of PLMS and PLMW in narcolepsy, an association between the presence of PLMS and measures of REM sleep and daytime functioning disruption. These results suggest that PLMS represent an intrinsic feature of narcolepsy.

The development of antibodies directed against factor VIII (FVIII) represents a major hurdle in the treatment of hemophilia A. Most anti-FVIII antibodies are identified through their ability to inhibit the FVIII procoagulant activity. Many of them, however, do not interfere with the functional properties of FVIII. Antibodies directed against the B domain belong to this latter category. Here, we characterized B domain-specific human monoclonal Abs (mAbs) at the molecular level. A series of human mAbs directed against FVIII was produced upon immunization of transgenic XenoMouse mice with human recombinant FVIII (rFVIII). Selection of the hybridoma with epitope specificity for the B domain was performed by differential recognition of full-length and B domain-deleted rFVIII. None of the anti-B domain mAbs demonstrated inhibitory activity against FVIII. Three of the mAbs recognized linear epitopes: mAb 25H3 bound to the (1014)HIDGPSLLIEN(1024) sequence; mAbs 8E3 and 22B6 shared the same epitope, composed of residues (1534)KWNEANR(1540). The corresponding soluble peptides inhibited the binding of their respective mAbs to FVIII. mAbs 8E3 and 22B6 displaced the binding of FVIII to vonWillebrand factor. Moreover, some of them (in particular mAbs 4G6 and 8E3) were able to compete for binding to the B domain with the anti-FVIII Abs from hemophilia A patients without inhibitor or with low Bethesda titers. Further investigation will allow to better characterize their clinical relevance.

Objectives: To assess heart rate (HR) and blood pressure (BP) changes associated with periodic leg movements during sleep (PLMS) with or without EEG signs of arousal in subjects with primary restless legs syndrome (RLS)., Methods: Ten patients with RLS (4 women, aged 47.3 +/- 13.5 years) underwent one night of polysomnography along with noninvasive beat-to-beat BP monitoring. Ten PLMS with microarousals (PLMS-MA) and 10 PLMS without microarousals (PLMS-noMA) were analyzed in each subject. Systolic and diastolic BP (SBP, DBP) were measured within a 25-beat temporal window comprising 10 beats before and 15 beats after onset of each movement. PLMS-related BP changes were assessed by repeated measures one-way analysis of variance. BP changes associated with PLMS-MA and PLMS-noMA were compared by paired t-tests. Pearson correlation coefficients were used to assess the relationship between cardiovascular changes and clinical and polysomnographic variables., Results: BP increased significantly in association with all PLMS (on average, SBP 22 mm Hg, DBP 11 mm Hg). BP changes associated with PLMS-MA were greater vs those associated with PLMS-noMA (p < 0.05). SBP and DBP changes increased with age and the duration of illness., Conclusions: Periodic leg movements-related repetitive nocturnal blood pressure fluctuations could contribute to the risk of cardiovascular diseases in patients with restless legs syndrome, especially in the elderly.

The International Classification of Sleep Disorders (ICSD-2) has separated sleep-related movement disorders into simple, repetitive movement disorders (such as periodic limb movements in sleep [PLMS], sleep bruxism, and rhythmic movement disorder) and parasomnias (such as REM sleep behavior disorder and disorders of partial arousal, e.g., sleep walking, confusional arousals, night terrors). Many of the parasomnias are characterized by complex behaviors in sleep that appear purposeful, goal directed and voluntary but are outside the conscious awareness of the individual and therefore inappropriate. All of the sleep-related movement disorders described here have specific polysomnographic findings. For the purposes of developing and/or revising specifications and polysomnographic scoring rules, the AASM Scoring Manual Task Force on Movements in Sleep reviewed background literature and executed evidence grading of 81 relevant articles obtained by a literature search of published articles between 1966 and 2004. Subsequent evidence grading identified limited evidence for reliability and/or validity for polysomnographic scoring criteria for periodic limb movements in sleep, REM sleep behavior disorder, and sleep bruxism. Published scoring criteria for rhythmic movement disorder, excessive fragmentary myoclonus, and hypnagogic foot tremor/alternating leg muscle activation were empirical and based on descriptive studies. The literature review disclosed no published evidence defining clinical consequences of excessive fragmentary myoclonus or hypnagogic foot tremor/alternating leg muscle activation. Because of limited or absent evidence for reliability and/or validity, a standardized RAND/UCLA consensus process was employed for recommendation of specific rules for the scoring of sleep-associated movements.

A meta-analysis assessing the magnitude of sleep changes from baseline in placebo-treated (psychological and pharmacological placebo) and untreated groups issued from independent trials was conducted. Comparisons were then performed to assess if the magnitude of sleep changes in the placebo control groups were significantly different than those of the untreated group. Medline, PsychInfo and Current Contents databases (1990-2004) were searched for primary insomnia treatment studies using a randomized controlled parallel-group design. Effect sizes were computed for each end-point variable based on subjective (patient-reported) and polysomnographic measures. Thirty-four studies (n = 1392 subjects) met inclusion criteria; twenty-three used a pharmacological placebo (n = 1163), four used a psychological placebo (n = 81), and seven used a waitlist condition (n = 148). Between-group comparisons were performed using a random effects model analysis. Significant pre-post changes were observed in the pharmacological placebo condition on several sleep parameters, both on objectively and subjectively measured outcomes [objective and subjective sleep onset latency (SOL) and total sleep time (TST) and subjective wake after sleep onset]. Although a tendency was observed for objective SOL, only the changes on subjective SOL and TST in the pharmacological placebo condition were significantly different from the corresponding changes in the untreated group. No differences were significant for the psychological placebo groups. Although the present findings suggest that sleep may significantly change in response to a pharmacological placebo, conclusions remain tentative because of possible confounds that may arise when comparing groups issued from different trials. Further research directly comparing placebo groups and untreated groups from the same randomized trials remains necessary.

A 95% yield in the cross metathesis of acrylonitrile with a model olefin is achieved at 25 degrees C with only 3 mol % of the new air-stable ruthenium catalyst 1f shown in the enclosed structural diagram. Even more remarkable are the performances of its boosted version 1g incorporating an electron-withdrawing group. Both these new enhanced versions of Hoveyda catalyst are readily available from Grubbs second generation precatalyst upon reaction with a styrenyl ether the end group of which has been functionalized by an ester function. The latter acts as a weakly coordinating ligand allowing to reach a desirable balance between antinomic properties such as the catalyst's stability, a high activity for challenging substrates, and a high initiation rate.

This article presents an overview of possible mechanisms associated with pain perception, with a specific focus on understanding unusual manifestations of orofacial pain associated with nerve insult. It includes recent evidence concerning neurobiological changes that occur in the periphery at tissue and nerve sites, or within the central nervous system, and that may involve chemical and inflammatory responses, sensitization, or alterations of cellular function. Moreover, the contribution of the autonomic nervous system, changes in emotional reactivity and vigilance, the roles of high brain centers such as the basal ganglia (nigro-striatal) system, and the influence of aging and gender, are briefly described.

An uncommon synergism in the concerted action of OH- and PR3 toward the simple Ru(II) complex Ru(CO)3Cl2(thf) allows a highly efficient reduction of the metal in ethanol or acetonitrile solution at 0 degrees C, with selective production of the corresponding Roper's-type Ru(0) complexes Ru(CO)2(PR3)3 in high yields within 10 min.

The development of anti-factor VIII (FVIII) antibodies is currently one of the most serious complications in the treatment of haemophilia A patients. Numerous studies in literature report on their epitope specificity, their mechanism of FVIII inactivation, and their relationship with FVIII genetic alterations. During the last two years, however, a particular effort has been made to better understand their generation, with particular emphasis on the interplay of T cells and B cells specific for FVIII and the generation of anti-FVIII antibodies. Moreover, novel strategies to improve the management or treatment of patients with anti-FVIII antibodies have been recently proposed: the use of less immunogenic engineered recombinant FVIII molecules, neutralization of inhibitors by blocking their deleterious activity either by low molecular weight peptide decoys or by anti-idiotypic antibodies, and attempts to suppress the T-cell response involved in the antibody formation. All of these represent promising therapeutic approaches. This review attempts to sum up current knowledge of the nature and properties of anti-FVIII antibodies, their mechanism of action, their neutralization by anti-idiotypic antibodies, and the role of T cells in FVIII inhibitor formation. In the final part, some of the new strategies susceptible to improve the management or the eradication of anti-FVIII antibodies are presented.

Study Objectives: Pain is a leading cause of sleep disturbances in medical illness. Providing effective analgesia is considered an important intervention to reduce these sleep disturbances. Opioids remain the treatment of choice to relieve postoperative pain in hospitalized patients. However, their effects on sleep in pain patients or normal subjects remain unclear, as previous studies have been conducted mainly with former opioid addicts. The purpose of this investigation was to evaluate and describe the effects of acute clinical doses of morphine on sleep in healthy pain-free subjects., Design: Subjects were randomly assigned to untreated (baseline), morphine (intravenous injections of 0.1 [DOSAGE ERROR CORRECTED] mg/kg), and placebo (intravenous injections of 0.9% NaCI) conditions., Setting: Sleep laboratory., Participants: Seven healthy pain-free, nonaddicts (5 women, 2 men; mean age = 25 +/- 1.6 years)., Measurements and Results: Standard polysomnographic sleep and respiratory variables were measured during 3 experimental conditions. The treatment effect was analyzed with a Latin square cross-over design followed, when appropriate, by Tukey contrasts. Morphine altered sleep architecture by reducing slow-wave sleep (non-rapid eye movement stages 3-4) and rapid eye movement sleep, and by increasing non-rapid eye movement stage 2 sleep. Results did not reveal any statistical differences for other sleep and respiratory variables., Conclusions: Similar to earlier findings in animals, nondependent opiate addicts, and postoperative patients, morphine was found to reduce duration of slow-wave sleep. Unlike previous reports, however, its acute administration produced a moderate reduction in rapid eye movement sleep and did not increase correlates of arousal (ie, awakenings, electroencephalogram arousals, wake after sleep onset). Future studies should correlate these findings in patients with pain and evaluate whether optimal pain relief with opioid therapy can improve sleep disturbances in pain patients.

The literature on sensory perception during sleep suggests that light sleep (Stage 2) is more responsive to external sensory stimulation (e.g. sound, electrical shock) than deep sleep (Stages 3 and 4) and REM sleep. The main objective of this study was to characterize the specificity of nociceptive stimulation to trigger sleep arousal-awakening over all sleep stages. Thirteen healthy adults (e.g. without pain or sleep problems; six female and seven male of a mean age of 24.2+/-1.3 years) were included in the study. The responses to noxious intramuscular 5% hypertonic infusion were compared to innocuous vibrotactile and to respective control stimulations: isotonic infusion and auditory stimulations. These stimulations were applied during wakefulness and were repeated during sleep. Polygraphic signals (e.g. brain activity, heart rate) signals were recorded to score sleep arousal over all sleep stages. A subjective assessment of sleep quality was made on next morning. No overnight sensitization or habituation occurred with any of the experimental stimulations. The vibratory-auditory stimulations and the noxious hypertonic infusions triggered significantly (P < 0.05) more awakenings in sleep Stage 2 and in REM than their respective control stimulations. In sleep Stage 2, both vibratory + auditory stimulations and the noxious hypertonic infusions has the same awakening response frequency (approximately 30%), however, with the noxious infusions the response frequency were similar in sleep Stages 3 and 4 (P < 0.05) and in REM (trend). Compared to the baseline night, sleep quality was lower following the night with noxious stimulation (90.1+/-2.7 and 73.3+/-7.4 mm, respectively; P < 0.03. These data suggest that pain during sleep could trigger a sleep awaking response over all sleep stages and not only in light sleep.

The prospective evaluation of the effect of thromboprophylaxis in women with one unexplained pregnancy loss from the 10th week of amenorrhea was performed. A total of 160 patients with heterozygous factor V Leiden mutation, prothrombin G20210A mutation, or protein S deficiency were given 5 mg folic acid daily before conception, to be continued during pregnancy, and low-dose aspirin 100 mg daily or low-molecular-weight heparin enoxaparin 40 mg was taken from the 8th week. Twenty-three of the 80 patients treated with low-dose aspirin and 69 of the 80 patients treated with enoxaparin had a healthy live birth (odds ratio [OR], 15.5; 95% confidence interval [CI], 7-34, P <.0001). Enoxaparin was superior to low-dose aspirin in each subgroup defined according to the underlying constitutional thrombophilic disorder. An associated protein Z deficiency and/or positive antiprotein Z antibodies were associated with poorer outcomes. The neonate weight was higher in the women successfully treated with enoxaparin, and neonates small for gestational age were more frequent in patients treated with low-dose aspirin. No significant side effects of the treatments could be evidenced in patients or newborns. As there is no argument to prove that low-dose aspirin may have been deleterious, these results support enoxaparin use during such at-risk pregnancies.

Maternal hypercoagulability is a possible cause of miscarriage during the eighth and ninth weeks of pregnancy, when the placenta replaces the yolk sac. We thus examined associations between putative markers of an acquired hypercoagulable state and the risk of first miscarriage. We conducted a case-control study comparing 743 women who miscarried in weeks 8 and 9 with 743 women who underwent a first provoked abortion, matched for age, number of pregnancies, and time elapsed since abortion. Levels of plasma homocysteine and of various antiphospholipid/antiprotein and hemostasis-related autoantibodies were categorized in 4 strata (percentiles 1-80, 81-95, 96-99, 100 among control patients) and analyzed in conditional logistic regression models. Pregnancy loss was independently associated with positive lupus anticoagulant (matched odds ratio [OR], 2.6; 95% confidence interval [CI], 1.1-6.0), high levels of immunoglobulin M (IgM) antibodies against cardiolipin (OR for percentile 100 versus 0-80, 3.5; CI, 1.2-10.1) and against phosphatidylethanolamine (OR, 4.7; CI, 1.9-12.1), high levels of IgG antibodies against annexin V (OR, 3.2; CI, 1.1-9.1) and against tissue-type plasminogen activator (OR, 19.5; CI, 7.9-48.0), and high homocystinemia (OR, 4.1; CI, 1.3-12.5). A first early pregnancy loss is associated with increased levels of several autoantibodies and of homocysteine.

Objective: Periodic leg movements during sleep (PLMS) are often associated with electroencephalographic (EEG) changes, such as microarousals (MA), and with heart rate (HR) variations. The aim of the present study was to evaluate the effects of age and gender on HR changes associated with PLMS in restless legs syndrome (RLS) patients., Methods: Forty-two RLS patients underwent one night of polysomnographic recordings. They were divided into 3 groups of 14 subjects (7 women and 7 men) according to age, i.e. young (25-40 years), middle-aged (41-55 years) and elderly (56-71 years) patients. The RR interval was calculated for 5 intervals before and 15 intervals after the onset of 50 PLMS in each patient., Results: PLMS were associated with HR changes characterized by a tachycardia followed by a bradycardia. However, a reduction in the tachycardia and the bradycardia was observed with age. Moreover, women showed a higher amplitude in the bradycardia than men. No age or gender difference was found for MA index and duration., Conclusions: This study showed age and gender differences in the magnitude of the HR changes associated with PLMS. The knowledge of HR variations during sleep, including rapid HR changes associated with sleep events such as PLMS or MA, may be helpful in understanding the potential mechanisms involved in the increased cardiac risk observed in elderly.

We describe six families in which associated high levels of coagulation factors (F) XI, FIX and FVIII (each with a plasma concentration higher than the 95th percentile found in a control group of 500 asymptomatic individuals: respectively, 135, 145 and 155 IU dL-1) were inherited as a dominant autosomic genetic traits. In these six families, this syndrome is associated with venous thromboembolic events (Odds ratio 41 [4.9-353], P = 0.0006). It seems to predispose to idiopathic events and, as age increases, is often associated with recurrence. First thrombotic episodes occur in young patients (50% of the carriers are symptomatic at the age of 32 years) and in women, can be unmasked by hormonal treatments, mainly oral contraceptives. The association of high levels of coagulation FXI, FIX and FVIII is thus a new rare high-risk inherited thrombophilia syndrome.

Pain is a symptom well known to disrupt numerous aspects of normal physical and psychological life, including work, social activities and sleep. In daily practice, general dentists and specialists are frequently confronted with issues concerning pain, as their patients seek management that integrates oral health with overall well-being. An example of a dental condition involving pain is temporomandibular disorder, which is one of the most common sources of chronic orofacial pain and which shares similarities with back pain in terms of intensity, persistence and psychosocial impact. The objective of this paper is to inform and aid the general dentist and the specialist concerned with the sleep quality of patients with orofacial pain.

Protein Z deficiencies have recently been described in women with unexplained early fetal loss. Using a new, specifically elaborated, commercially available enzyme-linked immunosorbent assay (ELISA), we performed a case-control study on anti-protein Z immunoglobulin G (IgG) and IgM antibodies in 191 nonthrombotic, nonthrombophilic women with consecutive pathologic pregnancies. Levels of anti-protein Z antibodies were categorized in 3 strata (percentiles 1 through 74, 75 through 97, 98 through 100 among controls). The 2 upper levels of IgG and IgM anti-protein Z antibodies were associated with the risk of unexplained recurrent embryo loss or fetal death independently from habitual antiphospholipid/anticofactor antibodies, and a dose-effect relationship between antibody levels and the clinical risks was evidenced. In women, enhanced immune-complex formation with protein Z may play a role in unexplained embryo losses and, from the 10th week of gestation, may favor hypercoagulability in the maternal placenta side.

Objective: To assess the frequency of periodic leg movements (PLM) in idiopathic REM sleep behavior disorder (RBD) and to analyze their polysomnographic characteristics and associated autonomic and cortical activation., Background: PLM during sleep (PLMS) and wakefulness (PLMW) are typical features of restless legs syndrome (RLS), but are also frequently observed in patients with RBD., Methods: Forty patients with idiopathic RBD underwent one night of polysomnographic recording to assess PLMS frequency. PLM features, PLMS-related cardiac activation during stage 2 sleep, and EEG changes were analyzed in 15 of these patients with RBD. Results were compared with similar data obtained in 15 sex- and age-matched patients with primary RLS., Results: Twenty-eight (70%) of 40 patients with RBD showed a PLMS index greater than 10. No between-group differences were found in sleep architecture or indexes of PLMW and PLMS during non-REM sleep, but a trend for a higher PLMS index during REM sleep was found in patients with RBD. PLM mean duration and interval in the two conditions were similar. A transient tachycardia followed by a bradycardia was observed in close association with every PLMS in both groups, but the amplitude of the cardiac activation was significantly reduced in patients with RBD. In addition, significantly fewer PLMS were associated with microarousal in this condition., Conclusions: Periodic leg movements are very common in idiopathic RBD, occurring in all stages of sleep, especially during REM sleep. In idiopathic RBD, the reduction of cardiac and EEG activation associated with PLMS suggests the presence of an impaired autonomic and cortical reactivity to internal stimuli.

It has been shown that realistic, localized painful sensations can be experienced in dreams either through direct incorporation or from past memories of pain. Nevertheless, the frequency of pain dreams in healthy subjects is low. This prospective study was designed to evaluate the occurrence and frequency of pain in the dreams of patients suffering from burn pain. Twenty-eight nonventilated burn victims were interviewed for 5 consecutive mornings during the first week of hospitalization. A structured-interview protocol was used to collect information on dream content, quality of sleep, and pain intensity and location. Patients were also administered the Impact of Event Scale to assess posttraumatic symptoms. Thirty-nine percent of patients reported 19 pain dreams on a total of 63 dreams (30%). Patients with pain dreams showed evidence of worse sleep, more nightmares, higher intake of anxiolytic medication, and higher scores on the Impact of Event Scale than did patents reporting dreams with no pain content. Moreover, patients with pain dreams also had a tendency to report more intense pain during therapeutic procedures. Although more than half of our sample did not report pain dreams, these results suggest that pain dreams do occur at a greater frequency in suffering populations than in normal volunteers. More importantly, dreaming about pain may be an added stress for burn patents and may contribute to both poor sleep and higher pain intensity, which could evolve into a cycle of pain-anxiety-sleeplessness.

Objectives: Heart rate (HR) is known to change in association to micro-arousals (MA) during sleep. The aim of the present study was to evaluate the effect of age on HR variations associated with MA., Methods: Thirty-two healthy subjects underwent one night of polysomnographic recording. They were divided into two groups of 16 subjects according to age i.e. young (20-35 years) and middle-aged (50-65 years). The R-R intervals were calculated for 11 heart beats (10 intervals) before and 15 heart beats after the onset of MA., Results: HR changes associated with MA were characterized by a tachycardia followed by a bradycardia in both young- and middle-aged subjects. However, middle-aged subjects showed a significant reduction in the amplitude of both tachycardia and bradycardia as compared to young subjects., Conclusions: This study revealed an age-related reduction in the amplitude of the HR changes associated with MA. These results may reflect a decline in parasympathetic functions and a higher risk of cardiovascular diseases with advancing age.

Restless legs syndrome (RLS) is a common sleep-related disorder principally characterised by leg paresthesia associated with an irresistible urge to move. A majority of RLS patients experience periodic leg movements during sleep (PLMS) and wakefulness. Pharmacological evidence suggests that RLS-PLMS may be caused by a central nervous system dopaminergic (DA) dysfunction. The aim of the present study was to evaluate the striatal pre- and postsynaptic DA status in patients suffering from both RLS and PLMS, by means of [123I] beta-CIT and [123I]IBZM SPECT respectively. Ten drug-naïve patients and ten age-matched controls participated in this study. All participants were recorded for at least one night of polysomnography before the SPECT studies. No difference was seen in DA transporter ([123I] beta-CIT) binding between RLS-PLMS patients (MD=4.89) and controls (MD=4.81; p=0.81). The study of the striatal D2-receptor binding ([123I]IBZM) revealed a significantly lower binding in patients (MD= 1.72) compared with controls (MD=1.85; p=0.006). These results support the hypothesis that a central DA dysfunction is involved in the physiopathology of RLS-PLMS. Several mechanisms may be responsible for the decrease of the D2-receptor binding. However, since [123I] beta-CIT binding is normal, a decreased number of D2-receptors or a decreased affinity of D2-receptors for [123I]IBZM is more likely than an increased level of synaptic DA with attendant downregulation of D2-receptors.

Restless legs syndrome (RLS) is defined by an irresistible need to move associated with leg paresthesia. Two additional features are essential for diagnosis: (1) worsening of symptoms at rest with temporary relief by activity, and (2) worsening of symptoms during the evening and/or during the night. The suggested immobilization test (SIT) has been developed to evaluate the presence of these criteria. This test quantifies leg movements and leg discomfort during a 1-hour period of immobility prior to bedtime. We used the SIT to evaluate the effects of immobility on leg discomfort and leg movements experienced by 19 patients with RLS and 19 control subjects. Results show that immobility significantly worsens both leg discomfort and periodic leg movements (PLM) in patients with RLS but not in controls. Patients with RLS showed a higher leg discomfort score (32.6 +/- 15.1 mm vs. 5.7 +/- 7.9 mm; P < 0.00001), a greater maximum leg discomfort value (63.4 +/- 27.4 mm vs. 13.7 +/- 23.0 mm; P < 0.00001) and a greater PLM index (88.4 +/- 62.6 vs. 10.4 +/- 20.6; P < 0.00004) than control subjects. These results further validate the use of the SIT as a diagnostic and research tool for RLS and confirm the contention of the International RLS study group that RLS symptoms worsen at rest., (Copyright 2001 Movement Disorder Society.)

Polysomnographic recordings and the Suggested Immobilization Test (SIT) are frequently used to support the clinical diagnosis of restless legs syndrome (RLS). The present study evaluated the discriminant power of 5 different parameters: (1) index of periodic leg movements during sleep (PLMS), (2) index of PLMS with an associated microarousal (PLMS-arousal), (3) index of PLM during nocturnal wakefulness (PLMW), (4) SIT PLM index and (5) mean subjective leg discomfort score during the SIT (SIT MDS) in 100 patients with idiopathic RLS and 50 healthy control subjects. Both groups differed significantly on each parameter studied. Furthermore, while the SIT PLM, the PLMS and the PLMS-arousal indices revealed a poor ability to discriminate patients from controls, the PLMW index and the MDS both showed high sensitivity (87 +/- 7 and 82 +/- 8, respectively) and specificity (80 +/- 11 and 84 +/- 10, respectively) for diagnosing RLS. The combination of these 2 parameters correctly classified 88% of all subjects with a sensitivity of 82% and a specificity of 100%., (Copyright 2002 S. Karger AG, Basel)

Objective: To evaluate the characteristics of leg movements experienced by patients with the restless legs syndrome (RLS) during wakefulness using the suggested immobilization test (SIT).Methods: Forty patients with primary RLS who showed an index of leg movements greater than 40 during the SIT were selected for these analyses.Results: In general, Coleman's criteria for scoring PLMS were appropriate for scoring leg movements during the SIT. However, a substantial number of leg movements lasted between 5 and 10 s, exceeding Coleman's maximum duration criterion. The other criteria used to score PLMS (i.e. movements separated by 4-90 s and occurring in series of four consecutive movements) allowed detection of more than 90% of all leg movements recorded during the SIT. The distribution of inter-movement intervals (IMI) suggests that a great majority of leg movements recorded during the SIT are periodic, with a modal value of IMI between 11-12 s.Conclusion: Considering that leg movements recorded during the SIT last longer than those occurring during sleep, we recommend using a duration criterion of 0.5-10 s for scoring the former. We also recommend using the same periodicity criteria for the SIT as those used for scoring PLMS.

Sleep disturbances are frequently reported in victims following burn injuries. This prospective study was designed to assess sleep quality and to examine its daily relationship to pain intensity within the first week of hospitalization. Twenty-eight non-ventilated patients were interviewed during 5 consecutive mornings (number of observations=140) to collect information about perceived quality of sleep (visual analogue scale, number of hours, number of awakenings, presence of nightmares). Pain intensity was assessed at rest (nighttime, morning, during the day) and following therapeutic procedures using a 0-10 numeric scale. Seventy-five percent of patients reported sleep disturbances at some point during the study although, in most patients, sleep quality was not consistently poor. Pooled cross-section regression analyses showed significant temporal relationships between quality of sleep and pain intensity such that a night of poor sleep was followed by a significantly more painful day. Pain during the day was not found to be a significant predictor of poor sleep on the following night. These results support previous findings that perceived quality of sleep following burn injury is poor. Moreover, they show a daily relationship between quality of sleep and acute burn pain in which poor sleep is linked to higher pain intensity during the day.

The compound [Ru3(mu-H)(mu3-eta2-ampy)(CO)9] (1; Hampy =2-amino-6-methylpyridine) reacts with diynes RC4R in THF at reflux temperature to give the ynenyl derivatives [Ru3(mu3-eta2-ampy)(mu-eta3-RC...CC-CHR)(mu-CO)2-(CO)6] (2: R=CH2OPh; 3: R=Ph). These products contain a 1,4-disubstituted butynen-3-yl ligand attached to two ruthenium atoms. The compound [Ru3(mu-eta2-ampy)[mu3-eta6-PhCC5(C...CPh)-HPh2](CO)7] (4), which contains an eta5-cyclopentadienyl ring and a bridging carbene fragment, has also been obtained from the reaction of 1 with diphenylbutadiyne. This compound arises from a remarkable [3+2] cycloaddition reaction of a preformed 1,4-diphenylbutynen-4-yl ligand with a triple bond of a second diphenylbutadiyne molecule. The reactivity of the ynenyl derivatives 2 and 3 with diynes and alkynes has been studied. In all cases, compounds of the general formula [Ru3(mu-eta2-ampy)[mu3-eta5-C(=CHR)C=CRCR1=CR2](CO)7] (5-17) have been obtained. They all contain a ruthenacyclopentadienyl fragment formed by coupling of the coordinated ynenyl ligand of 2 (R = CH2OPh) or 3 (R = Ph) with a triple bond of the new reagent (the CR1=CR2 fragment results from the incoming diyne or alkyne reagent). While most of the products derived from 2 have the alkenyl C=CHR fragment with a Z configuration (R cis to Ru), all the compounds obtained from 3 have this fragment with an E configuration. Except 2 and 3, all the cluster complexes described in this article have a five-electron donor ampy ligand attached to only two metal atoms, a coordination mode unprecedented in cluster chemistry.

Background: Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent apneas during sleep, resulting in repetitive hypoxemic episodes and interruptions of the normal sleep pattern. A previous study showed EEG slowing (ie, a higher ratio of delta + theta frequencies to alpha + beta frequencies on EEG) during rapid eye movement (REM) sleep and wakefulness in untreated OSAS patients. STUDY AND OBJECTIVES: To determine whether EEG slowing is reversible with continuous positive air pressure (CPAP) treatment and to verify whether the persistence of excessive daytime sleepiness (EDS) is correlated with residual slowing of the EEG., Patients: Ten healthy subjects (9 men and 1 woman) and 14 patients with moderate-to-severe OSAS (13 men and 1 woman) were studied before and after 6 months of treatment with CPAP., Results: Untreated OSAS patients showed EEG slowing in frontal and central cortical regions during both wakefulness and during REM sleep compared to healthy control subjects. This EEG slowing was found to be independent of time spent with arterial oxygen saturation < 90%, severity of OSAS, or mean sleep latency as determined by the multiple sleep latency test. CPAP treatment was found to correct the EEG slowing for both REM sleep and wakefulness. Daytime sleepiness also greatly improved with treatment, but some degree of somnolence remained., Conclusion: CPAP treatment was found to correct the EEG slowing that was observed in untreated OSAS patients. Persistent EDS may be related to persistent obesity after CPAP treatment.

Restless legs syndrome (RLS) is a neurologic disorder characterized principally by leg paresthesia and motor restlessness. Several clinical reports indicated that many patients with RLS also have arm paresthesia and restlessness. In the present study, the incidence of arm restlessness was assessed by questionnaire in 230 patients diagnosed with idiopathic RLS. Arm restlessness was reported by 48.7% of the patients. Patients with and without arm restlessness were compared with regard to clinical and polysomnographic parameters. No between-group differences were found for age at onset of RLS, duration of illness, gender, presence of a family history of RLS, sleep latency, total sleep time, sleep efficiency, and periodic leg movements index during sleep. However, arm restlessness was more frequent in patients with severe RLS. Interestingly, the polysomnographic data failed to differentiate the patients with arm restlessness from those without arm restlessness, except for sleep efficiency, which tended to be lower in patients with arm restlessness. In conclusion, the results of the present study are in agreement with clinical observations that a large proportion of patients with RLS have arm restlessness.

Although the interaction between sleep and pain is generating considerable interest (NIH Technology Assessment Panel, 1996), it is still unknown if chronic pain is the cause or effect of poor sleep. To further this understanding, subjects free of pain and sleep problems need to be studied in order to assess their response to pain during sleep, defined as a behavioral and a physiological state in which sensory processing is altered. (For example, while auditory perception remains active, other sensory inputs are facilitated, attenuated, or suppressed (Velluti, 199746 degrees C) was statistically greater in the lighter sleep stage 2 (48.3%) than in the deeper stages 3&4 (27.9%). A nocifensive behavioral-motor response was associated with only 2.5% of the 351 heat pain stimuli. Two other markers of sleep quality-sleep stage shift and awakening-were not influenced by the thermal stimuli. None of the subjects demonstrated any burns in the morning following the thermal stimulations applied during sleep. We conclude that the processing of nociceptive inputs is attenuated across sleep stages.

Sleep bruxism (SB) is a stereotyped movement disorder characterized by grinding or clenching of the teeth during sleep. The majority of the population will at some time during their lifetime grind or clench their teeth. It becomes a pathological condition when the subject presents severe tooth damage or complains of non-restorative sleep. The prevalence of SB is difficult to estimate, since quite often the subjects are unaware of having the disorder. There is no gender difference. SB is more frequent in the younger generation, with a decline over age. The symptom recognized in children can persist in adulthood. The aetio-pathophysiology is still unclear. SB has been associated with tooth interference, psychosocial and environmental factors, brain transmitters and basal ganglia dysfunction. Attempts have been made to specify the personality traits of bruxers, reported to be greater anxiety or vulnerability to stress; however, this is still controversial. SB subjects were observed to present vigilance-sleepiness and somatic problems. However, they are generally good sleepers. Some authors reported SB during all sleep stages, others observed the majority of bruxe episodes during light sleep and REM and often associated with arousal transients. No abnormalities of the autonomic nervous system could be shown in awake SB subjects. While some studies have shown an association between SB and PLM or breathing disorders, others did not confirm this. There is no specific treatment for SB: each subject has to be individually evaluated and treated. Three management alternatives are used: dental, pharmacological and psychobehavioural.

We just need to mix [Ru(CO)(3)Cl(2)(thf)] with methanolic NEt(4)OH-nature will do the rest: The unsaturated fragments thus generated spontaneously polymerize with production of CO(2) and H(2)O, which combine to give the carbonate ligands of the ruthena-crown species obtained (shown schematically). The carbonate groups, rarely seen in ruthenium carbonyl complexes, are responsible for the observed annulation, and hold consecutive Ru dimers together by acting as bridging and doubly chelating ligands.

Human adenoviruses are responsible for respiratory, gastroenteric and ocular infections and can serve as gene therapy vectors. They form icosahedral particles with 240 copies of the trimeric hexon protein arranged on the planes and a penton complex at each of the twelve vertices. The penton consists of a pentameric base, implicated in virus internalization, and a protruding trimeric fibre, responsible for receptor attachment. The fibres are homo-trimeric proteins containing an amino-terminal penton base attachment domain, a long, thin central shaft and a carboxy-terminal cell attachment or head domain. The shaft domain contains a repeating sequence motif with an invariant glycine or proline and a conserved pattern of hydrophobic residues. Here we describe the crystal structure at 2.4 A resolution of a recombinant protein containing the four distal repeats of the adenovirus type 2 fibre shaft plus the receptor-binding head domain. The structure reveals a novel triple beta-spiral fibrous fold for the shaft. Implications for folding of fibrous proteins (misfolding of shaft peptides leads to amyloid-like fibrils) and for the design of a new class of artificial, silk-like fibrous materials are discussed.