bluuebunny/crossref_metadata_2025 huggingface dataset:
Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia
Authors: WALKER M. M. , TALLEY N. J. , PRABHAKAR M. , PENNANEAC’H C. J. , ARO P. , RONKAINEN J. , STORSKRUBB T. , HARMSEN W. S. , ZINSMEISTER A. R. , AGREUS L.
Published: January 2009

Background  Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional disorders without defined pathology. Mast cells and eosinophils interact with T lymphocytes and may alter enteric nerve and smooth muscle function.

Aim  To examine mast cell, eosinophil and intraepithelial lymphocyte populations in duodenal biopsies of subjects with IBS and FD.

Methods  A random sample of an adult Swedish population (n = 1001; mean age 54 years; 51% female) underwent upper endoscopy and biopsy; 51 cases with FD and 41 cases with IBS were compared with 48 randomly selected controls. Eosinophils were identified by light microscopy; mast cells by immunocytochemistry (CD117). Intraepithelial lymphocytes were counted per 100 enterocytes. Cell counts were quantified by counting the number per high power field (HPF) in 5HPFs in the bulb (D1) and second part of duodenum (D2), summed over 5HPFs at each site.

Results  Cases and controls showed similar demographics. Compared to controls, IELs in IBS‐constipation were significantly increased (P = 0.005). Mast cells were significantly increased in IBS in D2 (P < 0.001), while eosinophils were significantly increased in FD in D1 and D2 (P < 0.001).

Conclusion  Duodenal mast cell hyperplasia is linked to IBS and eosinophilia to FD, and duodenal biopsy may identify subsets of these disorders.
Review article: hyperammonaemic and catabolic consequences of upper gastrointestinal bleeding in cirrhosis
Authors: DAMINK S. W. M. OLDE , DEJONG C. H. C. , JALAN R.
Published: January 2009

Background  Upper gastrointestinal (UGI) bleeding in patients with cirrhosis of the liver induces hyperammonaemia and leads to a catabolic cascade that precipitates life‐threatening complications. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and contains high amounts of leucine and valine. UGI bleed therefore presents the gut with protein of very low biologic value, which may be the stimulus to induce net catabolism.

Aim  To describe the hyperammonaemic and catabolic consequences of UGI bleeding in cirrhosis.

Methods  A semi‐structured literature search was performed using PubMed and article references.

Results  It has recently been proven that (‘simulation of ’) a UGI bleed in patients with cirrhosis leads to impaired protein synthesis that can be restored by intravenous infusion of isoleucine. This may have therapeutic implications for the function of rapidly dividing cells and short half‐life proteins such as clotting factors. Renal and small bowel ammoniagenesis were shown to be the most prominent causes for the hyperammonaemia that resulted from a UGI bleed. This provides an explanation for the therapeutic failure of the current clinical therapies that are aimed at large bowel‐derived ammonia production. Isoleucine infusion did not diminish renal ammoniagenesis.

Conclusions  New pharmacological therapies to diminish postbleeding hyperammonaemia should target the altered inter‐organ ammonia metabolism and promote ammonia excretion and/or increase the excretion of precursors of ammoniagenesis, e.g. l‐ornithine–phenylacetate.
Increased health costs from mandated Therapeutic Substitution of proton pump inhibitors in British Columbia
Authors: SKINNER B. J. , GRAY J. R. , ATTARA G. P.
Published: January 2009

Background  In 2003, British Columbia’s PharmaCare programme implemented a drug reimbursement policy called Therapeutic Substitution, which required patients with acid‐related diseases, primarily gastro‐oesophageal reflux disease (GERD), to make a medically unnecessary switch from their prescribed proton pump inhibitor (PPI) to the cheapest available brand name PPI (Pariet, rabeprazole sodium), comprising a different (nongeneric) chemical.

Aim  To evaluate the independent effects of PPI Therapeutic Substitution on individual healthcare utilization among those complying with the policy.

Methods  We used the BC Ministry of Health Services’ individual‐level linked data, allowing isolation of healthcare utilization for the entire population of PPI consumers from 2002 to 2005.

Results  After controlling for individual case variation in age, gender and a proxy for pre‐existing health status, regression analysis revealed statistically significant greater overall use of PPIs, physician services and hospital services independently associated with patients who complied with Therapeutic Substitution. Over the 3‐year period 2003–2005, this represented net healthcare expenditures totalling approximately C$43.51 million (C$9.11 million in total PPI drug expenditures, C$24.65 million for physician services and C$9.75 million for hospital services).

Conclusion  Medically unnecessary drug switching caused by compliance with Therapeutic Substitution policy appears to be independently associated with higher overall healthcare utilization.
Predictors of persistence with 5‐aminosalicylic acid therapy for ulcerative colitis
Authors: KANE S. V. , ACCORTT N. A. , MAGOWAN S. , BRIXNER D.
Published: January 2009

Background  Individuals with ulcerative colitis (UC) are at risk for poor persistence with therapy.

Aim  To identify factors predicting persistence with 5‐aminosalicylic acid (5‐ASA) therapy after 3 and 12 months in subjects with UC.

Methods  In this retrospective cohort study, persistence with 5‐ASA therapy was determined from prescription refill data from a commercial health insurance claims database. The analysis included subjects with UC who filled a prescription for any oral 5‐ASA between October 2002 and September 2004. Persistence was defined as prescription refill at 3 and/or 12 months. Multivariate logistic regression modelling identified variables independently associated with persistence at 3 and 12 months.

Results  In all, 3574 subjects were identified. Fifty‐seven per cent (2044) were persistent at 3 months. Glucocorticoid use before the index prescription predicted improved persistence at 3 months. Psychiatric diagnosis, mail order of the index prescription, female gender and co‐pay predicted decreased persistence. At 12 months, 1124 (55%) remained persistent. Rectal 5‐ASA use, older age and switching to a different 5‐ASA predicted improved persistence at 12 months. Hospitalization for a gastrointestinal condition, mail order of the 3‐month prescription and number of co‐morbid illnesses predicted lower persistence.

Conclusion  Persistence with 5‐ASA treatment in UC is complex and multifactorial, and differs by time period.
Interaction between psychiatric and autoimmune disorders in coeliac disease patients in the Northeastern United States
Authors: GARUD S. , LEFFLER D. , DENNIS M. , EDWARDS‐GEORGE J. , SARYAN D. , SHETH S. , SCHUPPAN D. , JAMMA S. , KELLY C. P.
Published: January 2009

Background  Previous studies yielded conflicting results regarding the presence of an association between coeliac disease (CD) and psychiatric disorders including depression. This association has not been studied in the United States.

Aim  To determine the prevalence of psychiatric and autoimmune disorders in patients with CD in the US compared with control groups.

Methods  In a case control study, the prevalence of psychiatric and autoimmune disorders was compared in 600 CD patients, 200 irritable bowel syndrome (IBS) patients and 200 healthy controls.

Results  The prevalence of depression in CD was 17.2% and was similar to that in IBS (18.5%, P = 0.74) and controls (16.0%, P = 0.79). Among CD patients, type I diabetes mellitus (DM) was identified as a significant risk factor for depression (P < 0.01) with 37% of patients with both CD and type I DM having clinical depression.

Conclusion  The prevalence of depression in CD is similar to that in other chronic gastrointestinal diseases and healthy controls. However, there is a markedly elevated risk of depression in patients with both type I DM and CD. Differing rates of type 1 DM among coeliac populations may account for disparity in published rates of depression in patients with CD.
Mitochondrial DNA‐based analysis of genetic variation and relatedness among Sri Lankan indigenous chickens and the Ceylon junglefowl (Gallus lafayetti)
Authors: Silva P. , Guan X. , Ho‐Shing O. , Jones J. , Xu J. , Hui D. , Notter D. , Smith E.
Published: January 2009

Indigenous chickens (IC) in developing countries provide a useful resource to detect novel genes in mitochondrial and nuclear genomes. Here, we investigated the level of genetic diversity in IC from five distinct regions of Sri Lanka using a PCR‐based resequencing method. In addition, we investigated the relatedness of IC to different species of junglefowls including Ceylon (CJF; Gallus lafayetti), a subspecies that is endemic to Sri Lanka, green (Gallus varius), grey (Gallus sonneratii) and red (Gallus gallus) junglefowls. A total of 140 birds including eight CJF were used to screen the control region of the mitochondrial DNA sequence for single nucleotide polymorphisms (SNPs) and other variants. We detected and validated 44 SNPs, which formed 42 haplotypes and six haplogroups in IC. The SNPs observed in the CJF were distinct and the D‐loop appeared to be missing a 62‐bp segment found in IC and the red junglefowl. Among the six haplogroups of IC, only one was region‐specific. Estimates of haplotype and nucleotide diversities ranged from 0.901 to 0.965 and from 0.011 to 0.013 respectively, and genetic divergence was generally low. Further, variation among individuals within regions accounted for 92% of the total molecular variation among birds. The Sri Lankan IC were more closely related to red and grey junglefowls than to CJF, indicating multiple origins. The molecular information on genetic diversity revealed in our study may be useful in developing genetic improvement and conservation strategies to better utilize indigenous Sri Lankan chicken resources.
Abnormal vascular reactivity at rest and exercise in obese boys
Authors: Karpoff L. , Vinet A. , Schuster I. , Oudot C. , Goret L. , Dauzat M. , Obert P. , Perez‐Martin A.
Published: January 2009

Background  Obese children exhibit vascular disorders at rest depending on their pubertal status, degree of obesity, and level of insulin resistance. However, data regarding their vascular function during exercise remain scarce. The aims of the present study were to evaluate vascular morphology and function at rest, and lower limb blood flow during exercise, in prepubertal boys with mild‐to‐moderate obesity and in lean controls.

Materials and methods  Twelve moderately obese prepubertal boys [Body Mass Index (BMI: 23·9 ± 2·6 kg m−2)] and thirteen controls (BMI:17·4 ± 1·8 kg m−2), matched for age (mean age: 11·6 ± 0·6 years) were recruited. We measured carotid intima‐media thickness (IMT) and wall compliance and incremental elastic modulus, resting brachial flow‐mediated dilation (FMD) and nitrate‐dependent dilation (NDD), lower limb blood flow during local knee‐extensor incremental and maximal exercise, body fat content (DEXA), blood pressure, blood lipids, insulin and glucose.

Results  Compared to lean controls, obese boys had greater IMT (0·47 ± 0·06 vs. 0·42 ± 0·03 mm, P < 0·05) but lower FMD (4·6 ± 2·8 vs. 8·8 ± 3·2%, P < 0·01) in spite of similar maximal shear rate, without NDD differences. Lower limb blood flow (mL min−1·100 g−1) increased significantly from rest to maximal exercise in both groups, although obese children reached lower values than lean counterparts whatever the exercise intensity.

Conclusions  Mild‐to‐moderate obesity in prepubertal boys without insulin resistance is associated with impaired endothelial function and blunted muscle perfusion response to local dynamic exercise without alteration of vascular smooth muscle reactivity.
SAP‐1 is a microvillus‐specific protein tyrosine phosphatase that modulates intestinal tumorigenesis
Authors: Sadakata Hisanobu , Okazawa Hideki , Sato Takashi , Supriatna Yana , Ohnishi Hiroshi , Kusakari Shinya , Murata Yoji , Ito Tomokazu , Nishiyama Uichi , Minegishi Takashi , Harada Akihiro , Matozaki Takashi
Published: January 2009

SAP‐1 (PTPRH) is a receptor‐type protein tyrosine phosphatase (RPTP) with a single catalytic domain in its cytoplasmic region and fibronectin type III‐like domains in its extracellular region. The cellular localization and biological functions of this RPTP have remained unknown, however. We now show that mouse SAP‐1 mRNA is largely restricted to the gastrointestinal tract and that SAP‐1 protein localizes to the microvilli of the brush border in gastrointestinal epithelial cells. The expression of SAP‐1 in mouse intestine is minimal during embryonic development but increases markedly after birth. SAP‐1‐deficient mice manifested no marked changes in morphology of the intestinal epithelium. In contrast, SAP‐1 ablation inhibited tumorigenesis in mice with a heterozygous mutation of the adenomatous polyposis coli gene. These results thus suggest that SAP‐1 is a microvillus‐specific RPTP that regulates intestinal tumorigenesis.
Trypanosoma cruziand myoid cells from seminiferous tubules: interaction and relation with fibrous components of extracellular matrix in experimental Chagas’ disease
Authors: Carvalho Luiz Otávio Pereira , Abreu‐Silva Ana Lucia , Hardoim Daiana de Jesús , Tedesco Roberto Carlos , Mendes Verônica Gonçalves , Da Costa Sylvio Celso Gonçalves , Calabrese Kátia da Silva
Published: January 2009

The main transmission route of Trypanosoma cruzi is by triatomine bugs. However, T. cruzi is also transmitted through blood transfusion, organ transplantation, ingestion of contaminated food or fluids, or is congenital. Sexual transmission, although suggested since the discovery of Chagas’ disease, has remained unproven. Sexual transmission would require T. cruzi to be located at the testes and ovaries. Here we investigated whether T. cruzi is present in the gonads of mice infected with 104T. cruzi trypomastigotes from the CL strain. Fourteen days after experimental infection, histopathological examination showed alterations in the extracellular matrix of the lamina propria of the seminiferous tubules. Furthermore, amastigotes were present in seminiferous tubules, within myoid cells, and in the adjacencies of the basal compartment. These results indicate that T. cruzi is able to reach seminiferous tubule lumen, thus suggesting that Chagas’ disease could potentially be transmitted through sexual intercourse. Complementary studies are required to demonstrate that Chagas’ disease can be transmitted by coitus.
Short‐term memory, alertness and performance: a reappraisal of their relationship to body temperature
Authors: JOHNSON M. P. , DUFFY J. F. , DIJK D. J. , RONDA J. M. , DYAL C. M. , CZEISLER C. A.
Published: January 2009

SUMMARY  Previous studies have led to the beliefs: (1) that short‐term memory is best during the night when the body temperature is at its nadir, and (2) that the circadian rhythms of short‐term memory and subjective alertness are driven by oscillators independent from each other and from the body temperature cycle. Unfortunately, these conclusions, which would have major implications for understanding the organization of the human circadian timing system, are largely based on field and laboratory studies, which in many cases sampled data infrequently and/or limited data collection to normal waking hours. In order to investigate these points further, we have monitored behavioural variables in two different protocols under controlled laboratory conditions: (1) during a period of 36–60 h of sustained wakefulness; and (2) during forced desynchrony between the body temperature and sleep/wake cycles, allowing testing of non‐sleep‐deprived subjects at all circadian phases. Contrary to earlier findings, we report here that the circadian rhythm of short‐term memory varies in parallel with the circadian rhythms of subjective alertness, calculation performance, and core body temperature under both these experimental conditions. These results challenge the notion that short‐term memory is inversely linked to the body temperature cycle and suggest that the human circadian pacemaker, which drives the body temperature cycle, is the primary determinant of endogenous circadian variations in subjective alertness and calculation performance as well as in the immediate recall of meaningful material.
Relationship between REM sleep latency and nocturnal cortisol concentrations in depressed patients
Authors: POLAND RUSSELL E. , McCRACKEN JAMES T. , LUTCHMANSINGH PREETAM , TONDO LEONARDO
Published: January 2009

SUMMARY  Due to conflicting reports on the possible association between shortening of rapid eye movement (REM) latency and increased cortisol secretion in patients with severe depression, this study examined the relationship between REM sleep latency and nocturnal cortisol concentration in 12 outpatients with major depression. The results showed a significant inverse correlation (r=—0.71, P<0.01) between REM sleep latency and mean (23.00 hours‐03.00 hours) plasma cortisol concentration. Age and severity of depression did not contribute to the inverse relationship. REM activity and density during the first REM period showed no significant correlations with the cortisol measures. A review of the literature suggests that this relationship might be unique to subjects with major depression, and again raises the possibility that these biological disruptions may have a common neurochemical basis.
Slow wave activity and prior sleep/wakefulness on an irregular schedule
Authors: ÅKERSTEDT TORBJÖRN , GILLBERG MATS , FOLKARD SIMON
Published: January 2009

SUMMARY  Eight subjects were exposed to a sleep schedule of 8, 4, 2, or 0 h of night sleep (awakening at 07 hours) followed by ad lib sleep from 1100 hours. Stepwise multiple regression analysis showed that SWA per cycle was closely related to the amount of prior waking, the amount of prior napping and the amount of prior sleep in the same sleep episode. The homeostatic ‘factor S’ of the three‐process model of sleep regulation of Folkard and Åkerstedt predicted as much of the variance of SWA as did the three prior sleep/wake variables together. It was concluded that SWA is closely related to prior sleep/wake history and follows a course similar to that of recovery of alertness.
Extension of the Limit Cycle Reciprocal Interaction Model of REM cycle control. An integrated sleep control model
Authors: MASSAQUOI S. G. , McCARLEY R. W.
Published: January 2009

SUMMARY  The Limit Cycle Reciprocal Interaction Model (LCRIM) describes the stable interaction of REM‐promoting and REM‐antagonizing neurons which generates the periodic occurrence of REM sleep. The cycling of this physiological oscillator is subject to perturbation from excitatory input, referred to as E, which derives from other parts of the nervous system. An extended model is now proposed which combines the ultraradian REM regulation modelled by the LCRIM with the homeostatic regulation of slow‐wave activity modelled by the Two‐Process Models of Borbély, Achermann and Beersma. In addition, this integrated model extends the E construct to relate explicitly to both the REM and slow‐wave sleep control systems, and to have stochastic dynamics. Overall, the model generates qualitatively realistic SWA, REM and wake‐up patterns. However, its performance awaits quantitative validation.
Nocturnal plasma thyrotropin variations are related to slow‐wave sleep
Authors: GOICHOT B. , BRANDENBERGER G. , SAINI J. , WITTERSHEIM G. , FOLLENIUS M.
Published: January 2009

SUMMARY  The thyrotropin (TSH) nycthemeral pattern is known to be strongly influenced by sleep, but previous studies have failed to demonstrate any link between sleep structure and TSH variations. Using 10‐min blood sampling, nocturnal TSH profiles were analysed in 24 young healthy subjects during normal sleep. Six of the subjects then underwent a partial sleep deprivation experiment, sleep was permitted from 03.00 hours to 07.00 hours. Descending slopes of TSH values were observed for the first 20 minutes of SWS episodes, whereas no significant trend was found for other sleep stages. During the period of sleep deprivation, nocturnal TSH levels increased and then declined immediately after sleep onset; however, the association between SWS and descending TSH slopes persisted. This temporal concordance suggests that some particular mechanisms associated with SWS may modulate TSH release, or conversely that increasing TSH levels prevent the occurrence of SWS.
Sleep patterns of European expatriates in a dry tropical climate
Authors: MONTMAYEUR ALAIN , BUGUET ALAIN
Published: January 2009

SUMMARY  Night sleep in sedentary African subjects living in the sahelian zone lasts from 7 h to 8 h, with high amounts of slow‐wave sleep (SWS) and paradoxical sleep (PS), SWS being present in each sleep cycle. We report here on sleep patterns in 6 healthy male European expatriates (aged 32–39 years) living in the same tropical climate. Polysomnography was taken for 3 consecutive nights in February (mean ambient temperature, Ta: 29.5°C), March (Ta: 31.6°C) and May (Ta: 33.3°C). Comparisons between seasons were made with an analysis of variance, with P≥ 0.05.

Because of a first night effect, the first nocturnal recording was discarded. Total sleep time (TST) increased in May vs February and March (P<0.05). Stage 2 was shorter in March than in February (P < 0.001) and its proportion decreased from February to March (P<0.02) and from March to May (P<0.05). Conversely, SWS increased from February to March and March to May (duration, P< 0.001; proportion, P<0.05), due to an augmentation in stage 4 with more numerous and longer stage 4 phases. Stage 3 was also increased in May vs March. The latency to SWS was shorter in March. SWS was present in each sleep cycle. PS was high, but did not vary. The sleep pattern changes were directly correlated with Ta. In conclusion, Caucasians living in the tropics slept similarly to Africans. The seasonal sleep variations favour the hypothesis that SWS is increased when thermoregulatory processes are triggered, either through passive climatic heating or exercise‐induced hyperthermia.
The effects of sleep deprivation on divergent thinking and attention processes
Authors: WIMMER FRANK , HOFFMANN ROBERT F. , BONATO RICHARD A. , MOFFITT ALAN R.
Published: January 2009

SUMMARY  Twelve male undergraduate students were deprived of sleep for one night and were tested with a series of cognitive tasks. Their performance was compared to the performance of thirteen control subjects. Two hourly tasks and three occasional tasks were administered in order to examine cognitive performance following sleep loss. In an attempt to replicate the findings of Horne (1988a), the figural form of the Torrance Tests of Creative Thinking was administered. To explore the effects of short‐term sleep deprivation on attention, the following tasks were also administered: a working memory task, a trail‐making task, a vowel/consonant discrimination task, and a letter recognition task. Results of the Torrance test, trail‐making task and letter recognition task revealed decreases in cognitive abilities following sleep loss, although all tasks required less than 10 minutes to administer. The results of this study suggest that cognitive measures following sleep deprivation have not been adequately explored. Results support the hypothesis that sleep serves a function of cognitive restitution, particularly in the maintenance of attentional mechanisms.
All‐night dynamics of the human sleep EEG
Authors: AESCHBACH DANIEL , BORBÉLY ALEXANDER A.
Published: January 2009

SUMMARY  The dynamics of the sleep EEG were investigated by all‐night spectral analysis of 51 sleep records. Power density was calculated for 1‐Hz bins in the 0.25–25.0 Hz range. Values in non‐rapid‐eye‐movement sleep (NREMS) were higher than in REMS in the 0.25–16.0 Hz range, and lower in the 18.25–22.0 Hz range. Power density in the 0.25–12.0 Hz range showed a declining trend over the first four NREMS episodes, which, depending on the frequency bin, could be approximated by non‐linear or linear decay functions. In the frequency range of sleep spindles (12.25–15.0 Hz), power density in the 13.25–15.0 Hz band showed an increasing trend between NREMS episode 2 and NREMS episode 4. A correlation matrix of 25 1‐Hz bins revealed for NREMS a negative correlation between slow‐wave activity (SWA; 0.25–4.0 Hz) and activity in the spindle frequency range. This negative correlation was highest in the first NREMS episode and diminished progressively over the subsequent NREMS episodes. Within NREMS episodes, the values in the spindle frequency range showed a U‐shaped time course, the trough coinciding with a high level of SWA. By contrast, in both the early and late part of the episode the two types of activity changed in the same direction. The results are consistent with recent electrophysiological studies indicating that the establishment of NREMS is associated with a progressive hyperpolarization of thalamocortical neurons during which the membrane potential exhibits oscillations first in the spindle frequency range and then in the range of SWA.
Naltrexone improves blood gas patterns in obstructive sleep apnoea syndrome through its influence on sleep
Authors: FERBER C. , DUCLAUX R. , MOURET J.
Published: January 2009

SUMMARY  Endogenous opiates have been shown to depress ventilation, and could therefore play a role in sleep apnoea syndrome (SAS). Hence, opiate antagonists have been used to treat SAS. The improvement they seem to give in blood‐gas monitoring could derive either from a direct blocking of endorphins that inhibit respiration or else, indirectly, through an influence on sleep patterns. The present study used a double blind cross‐over protocol to investigate the relationships between the effects on blood‐gas and on sleep patterns of the oral opiate antagonist naltrexone in obstructive SAS. Sleep patterns and transcutaneous blood gas (tcPO2 and tcPCO2) were recorded in parallel. Control recordings, without treatment, were carried out over two nights, followed by two nights of recording after administration either of naltrexone followed by a placebo or of a placebo followed by naltrexone. The number of obstructive apnoea and hypopnoea events per hour of sleep (Apnoea‐Hypopnoea Index: AHI), of hypoxic events (defined as a tcPO2 fall of at least 10, 15 or 20 mm Hg) and of hypercapnic events (defined as a tcPCO2 increase of at least 5 mmHg) were counted. A Metabolic Suffering Index (MSI) was calculated, defined as the product of the number, duration and magnitude of hypoxic and hypercapnic events. Compared to placebo, naltrexone resulted in significant improvements in blood‐gas patterns for the duration and MSI of hypoxic events and for the number, duration and MSI of hypercapnic events. Likewise, compared to placebo, naltrexone induced significant decreases in total sleep time, slow‐wave sleep and rapid eye movement (REM) sleep, and, on the other hand, significant increases in total wake time and in the number of wakenings per hour of sleep (NW h‐1). Certain naltrexone‐linked blood‐gas improvements were closely correlated with certain of the sleep pattern changes: the decrease in number and duration of hypoxic events correlated with REM‐time decrease and the decrease in number and duration of hypercapnic events correlated with the increase in Nw h‐1. These findings suggest that the improvement in blood‐gas patterns induced by naltrexone in SAS may be mediated by sleep pattern effects: i.e. a decrease in REM‐time and an increase in intra‐sleep wakening.
A proposal for computer‐based sleep/wake analysis
Authors: KEMP BOB
Published: January 2009

SUMMARY  The task group on Signal Analysis within the EC Concerted Action ‘Methodology for the analysis of the sleep‐wakefulness continuum’ has proposed general guidelines for a computer‐based sleep analyser that would not suffer from the most conspicuous limitations of manual standard scoring. The proposal specifies a standard format for digitized polygraphic recordings, a basic structure of the analyser, and a graphical output format for the analysis results. These analysis results include all sleep/wake related signal characteristics, an on/off REM sleep/wake process, and a continuous‐scale NREM sleep/wake process, all with a time resolution of 1s. Several locally available sleep analysers were made to comply with these specifications and then applied to standardized digital polygraphic sleep recordings that were circulated among the laboratories. Analysis results were distributed, enabling evaluation of the local algorithms.
The importance of REM sleep for brain maturation
Authors: MIRMIRAN MAJID , VAN SOMEREN EUS
Published: January 2009

SUMMARY  A number of studies, some done by us, are reviewed concerning the function of foetal/neonatal REM sleep. The hypothesis is put forward that REM sleep in early life serves as an indicator for: (1) the degree of brain maturation, and (2) the promotion of further brain development. This hypothesis, although not exclusive, differs from: the original theory of Roffwarg et al. (1966) that REM sleep serves as “wakefulness” during the period in which wakefulness is limited; and also from the theory of Crick and Mitchson (1983—the “unlearning” hypothesis of REM sleep). As the functions of sleep in general, and REM sleep in particular, are still unclear, we hope this review will suggest new possibilities for future research.
Immediate‐early genes in spontaneous wakefulness and sleep: expression of c‐fos and NGFI‐A mRNA and protein
Authors: POMPEIANO MARIA , CIRELLI CHIARA , TONONI GIULIO
Published: January 2009

SUMMARY  We have recently shown that the expression of two immediate‐early genes, c‐fos and NGFI‐A, is strongly affected by sleep deprivation. In this work, we investigated c‐fos and NGFI‐A expression after periods of spontaneous wakefulness or sleep. We used in situ hybridization and immunocytochemistry to detect the corresponding mRNA and protein levels, respectively. A first group of rats (S‐L) was sacrificed during the light hours at the end of a long period of sleep. A second group (W‐L) was sacrificed under similar conditions, except that during the last half hour the animals had been spontaneously awake. A third group (W‐D) was sacrificed during the dark hours after a long period of continuous wakefulness. We found that c‐fos and NGFI‐A expression in several brain areas was increased in W‐L and W‐D rats with respect to S‐L rats. Some of these areas, including the cerebral cortex, basal ganglia, and colliculi, may have been activated by the increased sensory and motor activity associated with waking. The activation of other areas, such as the medial preoptic area of the hypothalamus and some brainstem nuclei, may be more directly related to sleep regulation. These results indicate that many regions showing an increased expression of immediate early genes after wakefulness induced by sleep deprivation are also activated by periods of spontaneous wakefulness.
The relationship between EEG delta activity and autonomic activity as measured by SCSB during daytime sleep
Authors: PULLI KATRIINA , HÄRMÄ MIKKO , HASAN JOEL , VÄRRI ALPO , LOULA PEKKA
Published: January 2009

SUMMARY  The aim of the present work was to study the applicability of the static‐charge‐sensitive bed (SCSB) method to sleep studies, by comparing autonomic nervous activity measured with the SCSB and EEG delta activity (0.5–2 Hz). Simultaneous polygraphic and SCSB measurements of the first sleep cycle (110 min) were recorded from seven subjects. The amount of delta activity filtered from the EEG was compared in 3 min epochs to an autonomic activity index (AAI) based on cardiac, respiratory and body movement activity.

Individual Spearman rank order correlation coefficients between delta amplitude and the AAI varied from 0.17 to ‐0.60. Therefore, it is concluded that the relationship between the delta activity and the AAI is not systematic enough for defining ‘depth’ of sleep at any point in time by using the AAI. However, on average, the SCSB differentiates high and low delta values quite well. With some further improvement of the scoring system the SCSB is a useful tool in comparative sleep studies.
Sleepiness after glucose in narcolepsy
Authors: BRUCK DOROTHY , ARMSTRONG STUART , COLEMAN GRAHAME
Published: January 2009

SUMMARY  The issue of whether a high carbohydrate intake affects sleepiness and sleep variables has been studied in normals but not in patients suffering from narcolepsy, despite anecdotal evidence that sugars may facilitate sleepiness in this population. This study investigated whether the intake of 50g glucose exacerbated sleepiness in narcolepsy subjects. A double‐blind cross‐over study, involving 12 narcolepsy subjects and 12 matched controls, measured behaviour after a light lunch supplemented with a drink of either 50g glucose or placebo (artificially sweetened drink). The main dependent variables were the performance and EEG measures from the Wilkinson Auditory Vigilance Task (WAVT) and sleep variables from a 45 minute nap. The results indicate that in the narcolepsy subjects glucose was associated with decreased wake duration, reduced sleep onset latency and more spontaneous and induced sleep stage changes during the WAVT, while the nap revealed an increased intensity of sleepiness after glucose as measured by the Polygraphic Score of Sleepiness. Eleven of the twelve narcolepsy subjects showed increased REM duration in the nap after glucose. The findings are discussed in relation to serotonin synthesis, basal sleepiness and possible irregularities in the action of insulin.
Masseter muscle activity in diagnosed sleep bruxists compared with non‐symptomatic controls
Authors: SJÖHOLM T. , LEHTINEN I. , HELENIUS H.
Published: January 2009

SUMMARY  All‐night polysomnographic recordings were made of clinically diagnosed sleep bruxists (n= 23) and non‐symptomatic controls (n= 6). The total duration of masseter contraction (MC) episodes during sleep was 11.6 minutes per night in bruxists and 6.6 in controls (P < 0.01). The mean frequency of MC episodes was 11.0 per hour of sleep in bruxists and 6.4 in controls (P<0.05). The mean relative amplitude of MC episodes reflecting clenching strength was 0.81 in bruxists and 0.56 in controls (P <0.01). The percentage distribution of mixed and phasic MC episodes was 94% among bruxists and 88% in controls. The remaining activity was classified as tonic in both groups. The subclassification of rhythmic jaw movements (RJM), defined as three or more separate rhythmic contractions during MC episode were also evaluated. The frequency of those MC episodes with RJM was 3.6 per hour of sleep in bruxists and 1.1 in controls (P < 0.001). The difference in the relative amplitude between the two study groups suggests that the amount of clenching force is the primary factor responsible for the harmful effects of sleep bruxism on the masticatory apparatus. The most significant difference was seen in those phasic and mixed MC episodes which also included the subclassification of rhythmic jaw movement. The result suggests that relative amplitude and rhythmicity of MC episodes can be used as a basis to confirm the diagnosis and to evaluate the treatment effects of suspected sleep bruxists.
Mechanical abdomino/heart/lung interaction
Authors: ROBOTHAM JAMES L. , TAKATA MASAO
Published: January 2009

SUMMARY  It is generally assumed that inspiration will enhance both superior and inferior vena cava (SVC and IVC) blood flows due to the decrease in right atrial pressure produced by the fall in intrathoracic pressure. However, inspiration can also increase abdominal pressure due to the descent of the diaphragm. Using a model of abdominal vascular zone conditions, analogous to pulmonary vascular zone conditions, the abdominal venous compartment can be viewed as either a capacitor (zone III abdomen) or as a collapsible Starling resistor (zone II abdomen). This dual nature of the abdominal venous bed can explain how an inspiratory increase in abdominal pressure can increase IVC flow with hypervolaemia, but increase IVC flow with hypovolaemia. Combined generalized increases in abdominal pressure and focal forces over the liver can be shown to be an essential element in the pathogenesis of a Kussmaul's sign. Increases in abdominal pressures produced by active diaphragmatic descent can increase the total IVC venous return by enhancing the splanchnic IVC flow under relatively hypervolaemic conditions, but decrease the total IVC venous return by impeding the non‐splanchnic IVC flow under hypo‐volaemic conditions. Results are presented which suggest that the concept of abdominal vascular zone conditions is useful to understand overall directions of changes in total and regional venous return during normal and obstructed breathing and may provide useful analysis of the haemodynamic events which occur in obstructive sleep apnoea.
An animal model of the relationship between systemic hypertension and repetitive episodic hypoxia as seen in sleep apnoea
Authors: FLETCHER EUGENE C.
Published: January 2009

SUMMARY  Multiple factors may be responsible for acute and chronic blood pressure changes during obstructive sleep apnoea. A popular hypothesis is that recurrent episodic hypoxia stimulates chemoreceptors which, in turn, cause sympathetically mediated vasoconstriction and perhaps long‐term vascular remodelling. Disruption of sleep architecture secondary to frequent arousals may also cause chronic stress which may contribute to diurnal hypertension. A less likely factor elevating blood pressure is the effect of abrupt intra‐thoracic pressure changes on venous return and cardiac output. The rat responds to chronic, recurrent episodic hypocapnic hypoxia (12‐s bursts of nitrogen followed by air into Plexiglas chambers, every 30 s, 7h d‐1, 2–4% nadir ambient oxygen) with sustained increase in diurnal blood pressure (10–14 mmHg). Subsequent studies reveal that carotid sinus nerve section (chemodener‐vation) and chemically induced peripheral sympathetic denervation with the neurotoxin 6‐OH dopamine both eliminate this blood pressure‐elevating effect of chronic episodic hypoxaemia. Using this model, Sprague‐Dawley rats have been challenged with both eucapnic hypoxia and asphyxia and failed to show an additional blood pressure elevation above that caused by hypoxia (hypocapnic) alone. It appears that hypocapnic hypoxia creates a maximal stimulus to the sympathetic nervous system to which the addition of hypercarbia does not increase the blood pressure response. An alternative explanation is that the rat has protective mechanisms that limit the diurnal blood pressure response from further increase.
Congestive heart failure and sleep apnoea—possible mechanisms and effect of CPAP therapy
Authors: GREENBERG HARLY E. , GENOVESE JOSEPH , HUBERFELD SEYMOUR , SCHARF STEVEN M.
Published: January 2009

SUMMARY  Sleep‐disordered breathing has been associated with increased cardiovascular morbidity and mortality. However, despite several plausible mechanisms whereby obstructive sleep apnoea might be associated with left ventricular dysfunction and congestive heart failure, only limited data exist linking those disorders. These studies are reviewed along with possible mechanisms leading to left ventricular dysfunction in obstructive sleep apnoea. Recent investigations demonstrating improvement in left ventricular function after CPAP therapy in patients with congestive heart failure are reviewed as well. Finally, new data are presented from an animal model of congestive heart failure demonstrating a beneficial effect of CPAP on cardiac index in association with a decline in systematic vascular resistance. Remarkably, these effects persisted even after CPAP was removed. Possible mechanisms whereby CPAP may lead to improvement in cardiac output are discussed.
Discordance between phylogenetics and coalescent‐based divergence modelling: exploring phylogeographic patterns of speciation in the Carex macrocephala species complex
Authors: KING MATTHEW G. , ROALSON ERIC H.
Published: January 2009

We fit a molecular data set, consisting of the rpL16 cpDNA marker and eight microsatellite loci, to the isolation‐with‐migration model as implemented in IMa to test a well‐supported phylogenetic hypothesis of relationships within the Carex macrocephala species complex (Cyperaceae). The phylogenetic hypothesis suggests C. macrocephala from North America is reciprocally monophyletic and is sister to a reciprocally monophyletic clade of C. kobomugi. The North American C. macrocephala and C. kobomugi clade form a sister clade with a lineage of Asian C. macrocephala, thereby forming a paraphyletic C. macrocephala species. Not only does the phylogenetic hypothesis suggest C. macrocephala is paraphyletic, but it also suggests that the two lineages which share a partially overlapping distribution, Asian C. macrocephala and C. kobomugi, are not the most closely related. To test these relationships, we used coalescent‐based population genetic models to infer divergence time for each lineage pair within the species complex. The coalescent‐based models account for the stochastic forces which drive population divergence, and can account for the lineage sorting that occurs prior to lineage divergence. A drawback to phylogenetic‐based phylogeographical analyses is that they do not account for stochastic lineage sorting that occurs between gene divergence and lineage divergence. By comparing the relative divergence time of the three main lineages within this group, Asian C. macrocephala, North American C. macrocephala, and C. kobomugi, we concluded that the phylogenetic hypothesis is incorrect, and the divergence between these lineages occurred during the Late Pleistocene epoch.
Survival in the Rockies of an endangered hybrid swarm from diverged caribou (Rangifer tarandus) lineages
Authors: McDEVITT ALLAN D. , MARIANI STEFANO , HEBBLEWHITE MARK , DECESARE NICHOLAS J. , MORGANTINI LUIGI , SEIP DALE , WECKWORTH BYRON V. , MUSIANI MARCO
Published: January 2009

In North America, caribou (Rangifer tarandus) experienced diversification in separate refugia before the last glacial maximum. Geographical isolation produced the barren‐ground caribou (Rangifer tarandus groenlandicus) with its distinctive migratory habits, and the woodland caribou (Rangifer tarandus caribou), which has sedentary behaviour and is now in danger of extinction. Herein we report on the phylogenetics, population structure, and migratory habits of caribou in the Canadian Rockies, utilizing molecular and spatial data for 223 individuals. Mitochondrial DNA analyses show the occurrence of two highly diverged lineages; the Beringian–Eurasian and North American lineages, while microsatellite data reveal that present‐day Rockies’ caribou populations have resulted from interbreeding between these diverged lineages. An ice‐free corridor at the end of the last glaciation likely allowed, for the first time, for barren‐ground caribou to migrate from the North and overlap with woodland caribou expanding from the South. The lack of correlation between nuclear and mitochondrial data may indicate that different environmental forces, which might also include human‐caused habitat loss and fragmentation, are currently reshaping the population structure of this postglacial hybrid swarm. Furthermore, spatial ecological data show evidence of pronounced migratory behaviour within the study area, and suggest that the probability of being migratory may be higher in individual caribou carrying a Beringian–Eurasian haplotype which is mainly associated with the barren‐ground subspecies. Overall, our analyses reveal an intriguing example of postglacial mixing of diverged lineages. In a landscape that is changing due to climatic and human‐mediated factors, an understanding of these dynamics, both past and present, is essential for management and conservation of these populations.
AgrD‐dependent quorum sensing affects biofilm formation, invasion, virulence and global gene expression profiles in Listeria monocytogenes
Authors: Riedel Christian U. , Monk Ian R. , Casey Pat G. , Waidmann Mark S. , Gahan Cormac G. M. , Hill Colin
Published: January 2009

The Listeria monocytogenes Agr peptide‐sensing system has been analysed by creating a deletion mutant in agrD, the structural gene for the putative quorum‐sensing peptide. The ΔagrD mutant displayed significantly reduced biofilm formation, a defect which could be restored by genetic or physical complementation. A reduced invasion of Caco‐2 intestinal epithelial cells was observed for the ΔagrD mutant while phagocytosis by THP‐1 macrophages was unaffected. Additionally, the level of internalin A (InlA) in the cell wall was decreased in the ΔagrD mutant. Expression profiling of virulence genes (hlyA, actA, plcA, prfA and inlA) identified a finely tuned regulation which resulted in an impaired virulence response in the ΔagrD mutant. The mutant is also significantly attenuated for virulence in mice, as revealed by bioluminescent in vivo imaging. On day 3 post infection, systemic dissemination to livers and spleens had occurred for the wild type, whereas the ΔagrD mutant remained localized to the liver. Microarray analysis identified 126 and 670 genes as significantly regulated in exponential and stationary phase respectively. The results presented here suggest that peptide sensing plays an important role in the biology of L. monocytogenes, with relevant phenotypes in both the saprophytic and parasitic lifecycles.
Boron isotope composition of melt inclusions from porphyry systems of the Central Andes: a reconnaissance study
Authors: Wittenbrink Jens , Lehmann Bernd , Wiedenbeck Michael , Wallianos Alex , Dietrich Andreas , Palacios Carlos
Published: January 2009

Quartz‐hosted melt inclusions from latite dykes of the Eocene El Salvador copper porphyry system in northern Chile display wide ranges in both boron concentration (15–155 p.p.m. B) and isotope composition (δ11B −7 to +12‰; n = 10), likely reflecting slab‐derived fluid input from seawater‐altered oceanic crust. In contrast, the major Miocene tin‐silver and tin porphyry systems in the Bolivian back‐arc region (Cerro Rico de Potosi, Chorolque, Llallagua) have distinctly different melt inclusion compositions with δ11B of −11.4 ± 2.7‰ (n = 10), and magmatic boron enrichment up to several hundred p.p.m. B. The `seawater' signature in the El Salvador melt inclusions explains the oxidized mineral assemblage of the copper porphyry system, as opposed to the more reduced nature of the Bolivian tin porphyry systems, which reflect intracrustal melting of pelitic rocks.
Natural variation in maize architecture is mediated by allelic differences at the PINOID co‐ortholog barren inflorescence2
Authors: Pressoir Gael , Brown Patrick J , Zhu Wenyan , Upadyayula Narasimham , Rocheford Torbert , Buckler Edward S , Kresovich Stephen
Published: January 2009

We characterized allelic variation at barren inflorescence2 (bif2), a maize co‐ortholog of the Arabidopsis PINOID protein kinase (PID), and tested for trait associations with bif2 in both an association mapping population of 277 diverse maize inbreds and in the inter‐mated B73 × Mo17 (IBM) linkage population. Results from the quantitative analyses were compared with previous reports of bif2 phenotypes in mutagenesis studies. All three approaches (association, linkage, and mutagenesis) detect a significant effect of bif2 on tassel architecture. Association mapping implicates bif2 in an unexpectedly wide range of traits including plant height, node number, leaf length, and flowering time. Linkage mapping finds a significant interaction effect for node number between bif2 and other loci, in keeping with previous reports that bif2;spi1 and Bif2;Bif1 double mutants produce fewer phytomers. The Mo17 allele is associated with a reduced tassel branch zone and shows lower expression than the B73 allele in hybrid B73–Mo17 F1 inflorescences, consistent with the complete absence of tassel branches in the bif2 knockout mutant. Overall, these data suggest that allelic variation at bif2 affects maize architecture by modulating auxin transport during vegetative and inflorescence development.