Spatial learning and memory deficits following exposure to 24 h of sleep fragmentation or intermittent hypoxia in a rat model of obstructive sleep apnea.

Obstructive sleep apnea is primarily characterized by hypoxemia due to frequent apneic episodes and fragmentation of sleep due to the brief arousals that terminate the apneic episodes. Though neurobehavioral deficits frequently accompany sleep apnea, the relative roles of hypoxia versus sleep fragmentation are difficult to separate in apneic patients. Here, we assessed cognitive function as measured by water maze in the Fischer/Brown Norway (FBN) rat, comparing 24 h of sleep interruption (SI) to 24 h of intermittent hypoxia (IH), in order to dissociate their relative contributions to cognitive impairment.

24 hours of sleep deprivation in the rat increases sleepiness and decreases vigilance: introduction of the rat-psychomotor vigilance task.

A novel animal-analog of the human psychomotor vigilance task (PVT) was validated by subjecting rats to 24 h of sleep deprivation (SD) and examining the effect on performance in the rat-PVT (rPVT), and a rat multiple sleep latency test (rMSLT). During a three-phase (separate cohorts) crossover design, vigilance performance in the rPVT was compared with 24 h SD-induced changes in sleepiness assessed by polysomnographic evaluation and the rMSLT. Twenty-four hours of SD was produced by brief rotation of activity wheels at regular intervals in which the animals resided throughout the experiment.

Assessing sleepiness in the rat: a multiple sleep latencies test compared to polysomnographic measures of sleepiness.

Sleepiness following 6 h of sleep deprivation (SD) was evaluated with a rat multiple sleep latencies test (rMSLT), and the findings were compared to conventional polysomnographic measures of sleepiness. The 6 h of SD was produced by automated activity wheels, and was terminated at either the end of the light period or at the beginning of the dark period. The rMSLT consisted of 5 min wakefulness induced by sensory stimulation followed by 25 min of freedom to sleep.

Gamma-band auditory steady-state responses are impaired in first episode psychosis.

Background: In chronic schizophrenia and chronic bipolar disorder, gamma band (30-100 Hz) auditory steady-state electroencephalogram responses (ASSRs) are reduced in power and phase locking, likely reflecting neural circuit dysfunction. Here we examined whether gamma ASSR deficits are also present at first hospitalization for psychosis.

Methods: Subjects were 16 first episode schizophrenia patients (SZ), 16 first episode affective disorder patients (AFF) (13 with bipolar disorder), and 33 healthy control subjects (HC).

Sleep fragmentation elevates behavioral, electrographic and neurochemical measures of sleepiness.

Sleep fragmentation, a feature of sleep apnea as well as other sleep and medical/psychiatric disorders, is thought to lead to excessive daytime sleepiness. A rodent model of sleep fragmentation was developed (termed sleep interruption, SI), where rats were awakened every 2 min by the movement of an automated treadmill for either 6 or 24 h of exposure. The sleep pattern of rats exposed to 24 h of SI resembled sleep of the apneic patient in the following ways: sleep was fragmented (up to 30 awakening/h), total rapid eye movement (REM) sleep time was greatly reduced, non-rapid eye movement (NREM) sleep episode duration was reduced (from 2 min, 5 s baseline to 58 s during SI), whereas the total amount of NREM sleep time per 24 h approached basal levels.

Assessment of Capacity to Consent to Treatment: Challenges, the "ACCT" Approach, Future Directions.

OBJECTIVE: To review approaches to assessing consent capacity in patients with neurocognitive or neuropsychiatric illness; to summarize the rationale behind our structured interview for consent capacity; and to outline questions for future research. METHOD: After reviewing legal and clinical literature, and empirically comparing three leading consent capacity instruments, we developed the Assessment of Capacity to Consent to Treatment (ACCT) interview and administered it to adults with dementia (n=20), schizophrenia (n=20), and controls (n=19). Capacity ratings by primary care clinicians and experts blind to the patients' status were obtained for a subsample.

Adenosine and sleep deprivation promote NF-kappaB nuclear translocation in cholinergic basal forebrain.

In our investigations related to the homeostatic sleep factor adenosine (AD), we previously demonstrated that the DNA-binding activity of the transcription factor NF-kappaB in rat cholinergic basal forebrain increased following 3 h of sleep deprivation (SD). However, the neurotransmitter nature of the cells and the SD-induced stimuli responsible for NF-kappaB activation were not defined. In this report, we demonstrate, using double labeling immunohistochemistry, that nuclear translocation of NF-kappaB occurs almost exclusively in the cholinergic neurons of the basal forebrain following 3 h of SD.

Experimental sleep fragmentation impairs attentional set-shifting in rats.

Study Objective: To evaluate the effect of experimental sleep fragmentation (sleep interruption; SI) on complex learning in an intradimensional-extradimensional (ID/ED) set-shifting task in rats.

Design: A sleep fragmentation paradigm of intermittent forced locomotion was validated in adult rats by examining electrographic effects. Discrimination task performances were assessed in rats following sleep fragmentation or 2 control conditions.

Stress-induced abnormalities in myocardial perfusion imaging that are not related to perfusion but are of diagnostic and prognostic importance.

Introduction: Certain stress-induced ancillary findings on myocardial perfusion scintigraphy increase the likelihood that the patient has coronary artery disease (CAD); furthermore, among CAD patients, they indicate more severe and extensive disease, placing these patients at higher risk for future cardiac events. Indeed, in studies with no obvious perfusion defect yet with serious CAD--for example, balanced ischemia--it can be these high-risk findings that necessitate invasive intervention.

Discussion: Besides reversible perfusion defects, such findings include increased pulmonary radiotracer uptake, transient cavity dilatation, increased end-diastolic or end-systolic volume, decreased post-stress ejection fraction, and increased right ventricular tracer uptake on stress images.

Antimyeloma activity of two novel N-substituted and tetraflourinated thalidomide analogs.

Thalidomide alone or in combination with steroids has significant activity in multiple myeloma (MM). However, given its teratogenic potential, analogs have been synthesized, retaining the anti-MM activity without these side effects. We examined the anti-MM activity of two thalidomide analogs, CPS11 and CPS49.

Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma.

Previous studies have demonstrated the in vitro and in vivo activity of CC-5013 (Revlimid), an immunomodulatory analog (IMiD) of thalidomide, in multiple myeloma (MM). In the present study, we have examined the anti-MM activity of rapamycin (Rapamune), a specific mTOR inhibitor, combined with CC-5013. Based on the Chou-Talalay method, combination indices of less than 1 were obtained for all dose ranges of CC-5013 when combined with rapamycin, suggesting strong synergism.

Phenotype of columnar-lined esophagus in rats with esophagogastroduodenal anastomosis: similarity to human Barrett's esophagus.

In rats, esophagogastroduodenal anastomosis (EGDA) without concomitant chemical carcinogen treatment can lead to columnar-lined esophagus (CLE) including metaplasia, dysplasia, and esophageal adenocarcinoma (EAC). This study describes the morphology and phenotypic features of CLE and EAC in the rat model and compares them with the corresponding lesions in human Barrett's esophagus (BE). Swiss roll preparations of esophagi of EGDA rats and biopsies from human BE containing specialized intestinal metaplasia (SIM) and EAC were examined.

A functional haplotype in the 5' flanking region of the factor VII gene is associated with an increased risk of coronary heart disease.

Aims: The aim of this study was to investigate associations between coronary heart disease risk and polymorphisms in the coagulation factor (F)VII gene in participants of a large prospective study.

Methods: One thousand nine hundred and fifty-seven men were genotyped for four FVII polymorphisms, -670A-->C, -402G-->A, a 10 base pair insertion at -323 (0 > 10) in the promoter, and R353Q in the structural gene. Associations among genotypes and estimated haplotypes, plasma FVII levels, and coronary heart disease risk were evaluated, and the function of the promoter polymorphisms was assessed in reporter gene assays.

Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep-wakefulness and prolonged wakefulness: an in vivo microdialysis study.

Increased activity of the histaminergic neurons of the posterior hypothalamus has been implicated in the facilitation of behavioral wakefulness. Recent evidence of reciprocal projections between the sleep-active neurons of the preoptic/anterior hypothalamus and the histaminergic neurons of the tuberomammillary nucleus suggests that histaminergic innervation of the preoptic/anterior hypothalamic area may be of particular importance in the wakefulness-promoting properties of histamine. To test this possibility, we used microdialysis sample collection in the preoptic/anterior hypothalamic area of cats during natural sleep-wakefulness cycles, 6 h of sleep deprivation induced by gentle handling/playing, and recovery sleep.

Trastuzumab cardiotoxicity: Speculations regarding pathophysiology and targets for further study.

Trastuzumab, a monoclonal antibody that is selective for cells that overexpress the erbB2 receptor protein tyrosine kinase, is a promising targeted therapy for the treatment of breast cancer. Surprisingly, toxic cardiovascular side effects were discovered in late-phase clinical trials, and these effects were most prominent when trastuzumab was combined with anthracycline chemotherapy. We review recent data focusing on how erbB2 monoclonal antibodies could exert a cardiotoxic effect through unique cardiomyocyte cell surface and intracellular structural features, and how an individual's cardiac susceptibility to erbB2 monoclonal antibodies may be dictated by the ability of erbB2 monoclonal antibodies to bind cardiomyocytes.

The role of genotype in determining the effects of cigarette smoking on pulmonary function.

The effect of cigarette smoking on pulmonary function is highly variable. Some heavy smokers retain normal pulmonary function and others experience profound pulmonary function loss. The role of genotype in this process is unknown.

Cardiotoxicity in signal transduction therapeutics: erbB2 antibodies and the heart.

Cardiotoxicity is a common and potentially devastating side effect of antineoplastic drug therapy. This empiric observation is seen as paradoxical given that the cardiomyocyte is considered to be a terminally differentiated cell. Despite the fact that these cells do not divide after birth, adult cardiomyocytes may become "innocent bystander" targets of anticancer drugs designed to interfere with cell signaling pathways in rapidly proliferating cells.