bluuebunny/crossref_metadata_2025 huggingface dataset:
Production, survival and nutritive value of the perennial legumes Dorycnium hirsutum and D. rectum subjected to different cutting heights
Authors: Bell L. W. , Moore G. A. , Ewing M. A. , Ryan M. H.
Published: February 2006

Dorycnium hirsutum and D. rectum are perennial legumes which may have potential for use as pastures for the control of groundwater recharge in southern Australia. Little is known about the quality of the forage of Dorycnium species for grazing livestock or how these species respond to cutting. The effect of cutting height on plant survival, production of dry matter (DM), the proportion of leaf, edible stem (approximately <5 mm diameter) and woody stem in the DM and the nutritive value of the edible components was investigated. Biomass above five cutting‐height treatments (uncut, ground level, 5–8 cm, 10–15 cm and 15–30 cm above ground level) was removed at 8‐week intervals from plots of D. hirsutum and D. rectum from September 2002 to July 2003. In both species, plants subjected to lower cutting height treatments produced less DM above the height of the cut than those cut at higher heights. DM production declined over time in all treatments. Plants cut to ground level failed to regrow after the second harvest in D. hirsutum and the fourth harvest in D. rectum. Thus, these Dorycnium species were susceptible to high severity defoliations at 8‐week intervals. Negligible inedible woody stem was present in regrowth of both species after 8 weeks but D. hirsutum regrowth had a higher proportion of leaf (0·72) than D. rectum (0·56). Plants left uncut accumulated a large proportion of inedible woody stem in the DM (0·69 in both species) by July 2003, particularly at the base of the plant. Edible DM from regrowth of D. hirsutum and D. rectum had crude protein (CP) concentrations of 120 and 150 g kg−1 DM; dry matter digestibility (DMD) values of 0·45 and 0·58; organic matter digestibility (OMD) values of 0·50 and 0·64; neutral‐detergent fibre (NDF) concentrations of 370 and 290 g kg−1 DM; and acid‐detergent fibre (ADF) concentrations of 260 and 210 g kg−1 DM, respectively. Medicago sativa, grown under similar conditions, had higher digestibility values (0·63 DMD and 0·66 OMD) and similar CP concentrations to D. rectum (140 g kg−1 DM), but higher concentrations of NDF and ADF (410 and 290 g kg−1 DM). Leaf material from both Dorycnium species had a higher nutritive value than edible stems, with DMD and OMD values of leaf of D. rectum being 0·68 and 0·74 respectively. Uncut plants had a much lower nutritive value of edible DM than the regrowth from cut treatments; older material was also of a lower nutritive value. The relatively low nutritive value of even the young regrowth of Dorycnium species suggests that forage quality is a major limitation to its use. Forage of Dorycnium species could be used during periods when other sources of forage are in short supply but infrequent grazing it is likely to produce forage of a low nutritive value.
Amount and quality of grass harvested for first‐cut silage for differing spring‐grazing frequencies of two mixtures of perennial ryegrass cultivars with contrasting heading date
Authors: Humphreys J. , O'Kiely P.
Published: February 2006

There are potential advantages and disadvantages associated with grazing spring perennial ryegrass swards designated for first‐cut silage. These may differ for intermediate‐heading (0·50 ear emergence in the second half of May) and late‐heading (0·50 ear emergence in the first half of June) cultivars. The interactions between cultivar type, spring‐grazing frequency, silage‐harvest date and year were examined in an experiment with a randomized complete block (n = 4) design with a factorial arrangement of treatments, conducted in Ireland. The factors were (i) two perennial ryegrass mixtures: intermediate‐ vs. late‐heading cultivars, (ii) three spring‐grazing regimes: no grazing, grazing in mid‐March or grazing in both mid‐March and mid‐April, (iii) four first‐cut silage‐harvest dates that were at c. 10‐d intervals from 19 May and (iv) 2 years (1998 and 1999). The effects of cultivar mixture on herbage mass of the swards in spring were small and not statistically significant. The late‐heading cultivars provided lower amounts of herbage dry matter for harvesting for first‐cut silage but herbage with higher in vitro organic digestibility values compared with intermediate‐heading cultivars. To achieve the same amount of herbage for silage, the late‐heading cultivars needed to be harvested 8 d later than the intermediate‐heading cultivars. Even with this delay in harvest date, the late‐heading cultivars had higher in vitro organic digestibility values than the intermediate‐heading cultivars. The late‐heading cultivars could be harvested up to 30 d later and produce a higher amount of herbage for first‐cut silage with similar digestibility values compared with the intermediate‐heading cultivars.
Extended sequence preferences for oligodeoxyribonucleotide activity
Authors: Lenert Petar , Goeken Adam J. , Ashman Robert F.
Published: February 2006

Synthetic type B phosphorothioate oligodeoxyribonucleotides (ODN) activate mouse B cells via Toll‐like receptor 9 (TLR9). Starting with closely related 15‐mer prototype ODN, the sequence requirements for stimulatory (ST‐) and inhibitory (IN‐) activity were contrasted, by measuring apoptosis protection, G1 entry and interleukin‐6 secretion. ST‐ODN and IN‐ODN differ in that (1) ST‐ODN require a 5′ T, (2) the central CG is obligatory, (3) CG must be flanked 3′ specifically by TT at the position where IN‐ODN have GG, and (4) IN‐ODN tolerate truncation of the 3′ end better than ST‐ODN. Features shared by ST‐ODN and IN‐ODN include (1) requiring CC adjacent to the 5′ end, and (2) avoiding CC immediately 5′ to the CG. This pattern is used to create a model of how ST‐ODN binding might function to aggregate TLR9 so as to initiate the signal, and how the 5′ ends of ST‐ODN and IN‐ODN compete for binding. Further justification for considering TLR9 to be the ODN receptor was provided by a demonstration that in HEK293 cells transfected with TLR9, the potency of a panel of ODN for activating NF‐κB roughly parallels that seen in the biological assays in mouse B cells.
Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4bp‐mediated C3b and C4b degradation
Authors: Wooster David G. , Maruvada Ravi , Blom Anna M. , Prasadarao Nemani V.
Published: February 2006

Meningitis caused by Escherichia coli K1 is a serious illness in neonates with neurological sequelae in up to 50% of survivors. A high degree of bacteremia is required for E. coli K1 to cross the blood–brain barrier, which suggests that the bacterium must evade the host defence mechanisms and survive in the bloodstream. We previously showed that outer membrane protein A (OmpA) of E. coli binds C4b‐binding protein (C4bp), an inhibitor of complement activation via the classical pathway. Nevertheless, the exact mechanism by which E. coli K1 survives in serum remains elusive. Here, we demonstrate that log phase (LP) OmpA+E. coli K1 avoids serum bactericidal activity more effectively than postexponential phase bacteria. OmpA–E. coli cannot survive in serum grown to either phase. The increased serum resistance of LP OmpA+E. coli is the result of increased binding of C4bp, with a concomitant decrease in the deposition of C3b and the downstream complement proteins responsible for the formation of the membrane attack complex. C4bp bound to E. coli K1 acts as a cofactor to factor I in the cleavage of both C3b and C4b, which shuts down the ensuing complement cascade. Accordingly, a peptide corresponding to the complement control protein domain 3 of C4bp sequence, was able to compete with C4bp binding to OmpA and cause increased deposition of C3b. Thus, binding of C4bp appears to be responsible for survival of E. coli K1 in human serum.
Phenotypic and functional characterization of human CD25+ B cells
Authors: Brisslert Mikael , Bokarewa Maria , Larsson Pia , Wing Kajsa , Collins L. Vincent , Tarkowski Andrej
Published: February 2006

We demonstrate that humans have a phenotypically and functionally distinct subset of B lymphocytes that express the interleukin (IL)‐2 receptor (IL‐2R) α‐chain, cluster of differentiation (CD) 25. We found that one‐third of the circulating CD20+ B cells expressed CD25 and, using fluorescence‐activated cell sorter (FACS) analysis, that these cells were significantly larger and more granulated than B cells not expressing CD25. The simultaneous expression of the other two subunits (CD122 and CD132) and the proliferative responses of cells expressing CD25 to IL‐2 suggested that, in addition to CD25, functional IL‐2 receptors were expressed on this cell population. CD25 expression on B cells was selectively up‐regulated by Toll‐like receptor 2 (TLR2), TLR4, and TLR9 ligands but not by a TLR3 ligand or Epstein–Barr virus (EBV) stimulation. Blockade of the nuclear factor (NF)‐κB pathway completely abolished CD25 up‐regulation by these B cells. Interestingly, CD25+ B cells expressed significantly higher levels of surface immunoglobulins but lacked the ability to secrete immunoglobulin (Ig), as compared with CD25− B cells. Furthermore, CD25+ B cells performed significantly better as antigen‐presenting cells in allogeneic mixed lymphocyte reactions (MLR), which may be a result of their expression of high levels of the costimulatory molecules CD27 and CD80. Finally, blocking of CD25 on B cells led to an almost total abrogation of MLR. Our results indicate that CD25+ B cells have distinct phenotypic and functional properties, including the ability to contribute to antigen presentation, which is linked to their expression of CD25. Finally, the differential regulation of CD25 expression via selective TLR ligands suggests a role for CD25+ B cells in bridging innate and acquired immune responses.
Diversified bursal medullary B cells survive and expand independently after depletion following neonatal infectious bursal disease virus infection
Authors: Withers David R. , Davison T. Fred , Young John R.
Published: February 2006

The primary immunoglobulin repertoire of chickens is generated not by gene rearrangement but by a subsequent process of gene conversion in proliferating immature B cells within the follicles of a specialized gut‐associated lymphoid organ, the bursa of Fabricius. Neonatal infection with infectious bursal disease virus can eliminate almost the entire bursal B‐cell compartment. Thereafter, two types of follicle reappear. Larger follicles, with rapidly proliferating B cells and normal structure, are correlated with partial recovery of antibody response. Smaller follicles, lacking distinct cortex and medulla, appear unable to produce antigen‐responsive B cells. To understand the genesis of the two types of follicle, we analysed their VL sequences and activation‐induced deaminase mRNA levels. The results provide a model of bursal repopulation in which surviving bursal stem cells generate new follicles with normal morphology and function, while surviving medullary B cells continue to proliferate slowly, under the influence of stromal cells, giving rise to the smaller follicles. The latter remain fixed in a stage of development incapable of further gene diversification.
Interferon‐αβ mediates partial control of early pulmonary Mycobacterium bovis bacillus Calmette–Guérin infection
Authors: Kuchtey John , Fulton Scott A. , Reba Scott M. , Harding Clifford V. , Boom W. Henry
Published: February 2006

The role of type I interferon (IFN‐αβ) in modulating innate or adaptive immune responses against mycobacterial infection in the lung is unclear. In this study we investigated the susceptibility of IFN‐αβ‐receptor‐deficient (IFN‐αβR–/–) mice to pulmonary infection with aerosolized Mycobacterium bovis bacillus Calmette–Guérin (BCG). During early infection (2–3 weeks), enhanced growth of BCG was measured in the lungs of IFN‐αβR–/– mice compared to wild‐type mice. However, during late infection the burden of BCG was similar in the lungs of IFN‐αβR–/– and wild‐type mice. Although control of BCG growth was delayed, recruitment and activation of T and natural killer cells, production of IFN‐γ, and cytokine expression were all similar in wild‐type and IFN‐αβR–/– mice. However, decreased expression of nitric oxide in bronchoalveolar lavage fluids from IFN‐αβR–/– mice correlated with enhanced growth of BCG. Bone marrow‐derived macrophages from IFN‐αβR–/– mice also produced less nitric oxide following infection with BCG in vitro. These findings suggest that IFN‐αβ contributes to innate immunity to pulmonary mycobacterial infection by augmenting production of nitric oxide.
Risk factors for testicular cancer – differences between pure non‐seminoma and mixed seminoma/non‐seminoma?
Authors: Aschim E. L. , Haugen T. B. , Tretli S. , Daltveit A. K. , Grotmol T.
Published: February 2006

The origin of testicular germ cell cancer (TGCC) is believed to be carcinoma in situ cells developed in utero. Clinically, TGCCs are divided into two major histological groups, seminomas and non‐seminomas, where the latter group includes non‐seminomatous TGCCs with seminomatous components (mixed S/NS TGCC). Recent studies, however, have suggested that non‐seminomas and mixed S/NS TGCCs could have certain differences in aetiology, and in this study the TGCCs were divided into three, rather than the conventional two histological groups. A large case‐control study was undertaken on data on all live‐born boys registered in the Medical Birth Registry of Norway during the period 1967–1998 (n = 961 396). Among these were 1087 TGCC cases registered in the Cancer Registry of Norway until February 2004. We found several risk factors for TGCC, including low parity, low gestational age, epilepsy and retained placenta. Several of the variables studied seemed to be risk factors for specific histological groups, e.g. parity 0 vs. 2 and low gestational age being associated with increased risk of non‐seminomas, but not of mixed S/NS TGCC, and low maternal age being associated with increased risk of mixed S/NS TGCC, but not of non‐seminomatous TGCC. Therefore, our results might suggest that non‐seminomas and mixed S/NS TGCCs have partially different risk factors, whose associations may be obscured by combining these two histological groups. The histological groups were not significantly different, however. Most of our findings on risk factors for TGCC are in agreement with at least some previous studies. An unexplainable exception is low birth weight being associated with reduced risk of TGCC in our study.
Molecular analysis of polymerase gamma gene and mitochondrial polymorphism in fertile and subfertile men
Authors: Harris T. P. , Gomas K. P. , Weir F. , Holyoake A. J. , McHugh P. , Wu M. , Sin Y. , Sin I. L. , Sin F. Y. T.
Published: February 2006

CAG trinucleotide repeat length in the nuclear polymerase gamma gene (POLγ) has been shown to be associated with men with reduced fertility. The present study investigated the frequency of CAG repeat length genotypes and three exonuclease motifs of the POLγ in relation to the frequency of mitochondrial nucleotide substitutions. DNA from semen samples of 93 normozoospermic men and 192 non‐normozoospermic men was isolated and the specific regions of the genes were amplified by polymerase chain reactions (PCR) and sequenced to identify mutations. The genotypic frequencies of pooled POLγ CAG repeat lengths, =10/≠10 heterozygotes and ≠10/≠10 homozygotes, were significantly different between normozoospermic and non‐normozoospermic men (p < 0.05), with non‐normozoospermic men having a slightly higher frequency of the =10/=10 genotypes. The allelic frequency for =10 is 0.79 and ≠10 is 0.21 for normozoospermic men and 0.85 and 0.15, respectively, for non‐normozoospermic men (p < 0.025). There was no mutation detected in the exonuclease motifs in all the samples tested. Eighty normozoospermic and 124 non‐normozoospermic semen samples were analysed for nucleotide substitutions in mitochondrial genes by PCR and sequencing. Heteroplasmic mutations were found in one azoospermic man, four asthenozoospermic men and two normozoospermic men. Only one asthenozoospermic man was heterozygous for the POLγ genotype. Of the 17 men with non‐synonymous nucleotide substitutions, 14 were homozygous for the POLγ genotype. Non‐normozoospermic men had twice as many nucleotide substitutions than normozoospermic men. However, there were no significant differences in the frequencies of nucleotide substitution and POLγ genotypes in the two groups of men.
Impaired decision making following 49 h of sleep deprivation
Authors: KILLGORE WILLIAM D. S. , BALKIN THOMAS J. , WESENSTEN NANCY J.
Published: February 2006

Sleep deprivation reduces regional cerebral metabolism within the prefrontal cortex, the brain region most responsible for higher‐order cognitive processes, including judgment and decision making. Accordingly, we hypothesized that two nights of sleep loss would impair decision making quality and lead to increased risk‐taking behavior on the Iowa Gambling Task (IGT), which mimics real‐world decision making under conditions of uncertainty. Thirty‐four healthy participants completed the IGT at rested baseline and again following 49.5 h of sleep deprivation. At baseline, volunteers performed in a manner similar to that seen in most samples of healthy normal individuals, rapidly learning to avoid high‐risk decks and selecting more frequently from advantageous low‐risk decks as the game progressed. After sleep loss, however, volunteers showed a strikingly different pattern of performance. Relative to rested baseline, sleep‐deprived individuals tended to choose more frequently from risky decks as the game progressed, a pattern similar to, though less severe than, previously published reports of patients with lesions to the ventromedial prefrontal cortex. Although risky decision making was not related to participant age when tested at rested baseline, age was negatively correlated with advantageous decision making on the IGT, when tested following sleep deprivation (i.e. older subjects made more risky choices). These findings suggest that cognitive functions known to be mediated by the ventromedial prefrontal cortex, including decision making under conditions of uncertainty, may be particularly vulnerable to sleep loss and that this vulnerability may become more pronounced with increased age.
Sleep hygiene and actigraphically evaluated sleep characteristics in children with ADHD and chronic sleep onset insomnia
Authors: VAN DER HEIJDEN KRISTIAAN B. , SMITS MARCEL G. , GUNNING W. BOUDEWIJN
Published: February 2006

In the present study we investigated sleep hygiene and actigraphically evaluated sleep in 74 medication‐naïve children, aged 6–12 years, with rigorously diagnosed attention‐deficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia (ADHD‐SOI) and 23 ADHD controls without insomnia (ADHD‐noSOI). Between‐group differences were analysed for lights out (sleep log), actigraphically evaluated sleep onset, sleep latency, total sleep duration, actual sleep time and sleep hygiene as measured with the Children's Sleep Hygiene Scale. We found a significant difference (P < 0.001) in mean (±SD) sleep onset between the ADHD‐SOI group (21:49 ± 0:56 h) and ADHD‐noSOI groups (20:41 ± 0:45 h). Sleep latency was significantly (P < 0.001) longer in ADHD‐SOI (00:53 ± 0:25 h) compared to ADHD‐noSOI (00:26 ± 0:25 h). The difference in total sleep duration between ADHD‐SOI (9:42 ± 0:44 h) and ADHD‐noSOI (10:09 ± 0:43 h) was not significantly different (P = 0.18). The group difference in actual sleep time was also not significant (8:43 ± 0:52 h in ADHD‐SOI versus 9:13 ± 1:16 h; P = 0.40). There was no significant difference (P = 0.17) in mean (±SD) total sleep hygiene score between the ADHD‐SOI (56.4 ± 10.5) and ADHD‐noSOI groups (53.0 ± 10.6). We conclude that there were differences in sleep onset and sleep latency in ADHD children with chronic SOI and those without insomnia; however, sleep hygiene practices were similar and did not relate to sleep characteristics.
Fatigue and shift work
Authors: SHEN JIANHUA , BOTLY LEIGH C. P. , CHUNG SHARON A. , GIBBS ALISON L. , SABANADZOVIC SKENDER , SHAPIRO COLIN M.
Published: February 2006

Shift work is a ubiquitous phenomenon and its adverse effects on workers’ physical and mental health have been documented. In the sleep literature, differentiating between the symptoms of fatigue and sleepiness, and developing appropriate objective and subjective measures, have become very important endeavors. From such research, fatigue and sleepiness have been shown to be distinct and independent phenomena. However, it is not known whether shift work differentially affects fatigue and sleepiness. In an attempt to answer this question, 489 workers from a major Ontario employer completed a series of subjective, self‐report questionnaires, including the Fatigue Severity Scale (FSS) and the Epworth Sleepiness Scale. Workers were separated into four groups based on the frequency with which they are engaged in shift work (never, fewer than four times per month, 1–2 days per week, 3 days or more per week). The frequency of shift work was found to have a significant effect on subjective fatigue, but not on subjective sleepiness. Compared with the subjects who never had a shift schedule, those who worked in a shift for 3 days or more had significantly higher mean score of the FSS. In agreement with previous results, a low correlation was found between workers’ subjective fatigue and sleepiness scores, providing further support for the concept of fatigue and sleepiness as distinct and independent phenomena. Future research should address the possibility of using the FSS as an indicator when the frequency of shift work has become high enough to adversely affect work performance or cause health problems.
Sleep‐disordered breathing in a general heart failure population: relationships to neurohumoral activation and subjective symptoms
Authors: RAO ARCHANA , GEORGIADOU PANAGIOTA , FRANCIS DARREL P. , JOHNSON ANDREW , KREMASTINOS DIMITRIS TH. , SIMONDS ANITA K. , COATS ANDREW J. S. , COWLEY ALAN , MORRELL MARY J.
Published: February 2006

The aim of this study was to determine the prevalence of sleep‐related breathing disorders (SDB) in a UK general heart failure (HF) population, and assess its impact on neurohumoral markers and symptoms of sleepiness and quality of life. Eighty‐four ambulatory patients (72 male, mean (SD) age 68.6 (10) yrs) attending UK HF clinics underwent an overnight recording of respiratory impedance, SaO2 and heart rate using a portable monitor (Nexan). Brain natriuretic peptide (BNP) and urinary catecholamines were measured. Subjective sleepiness and the impairment in quality of life were assessed (Epworth Sleepiness Scale (ESS), SF‐36 Health Performance Score). SDB was classified using the Apnoea/Hypopnoea Index (AHI). The prevalence of SDB (AHI > 15 events h−1) was 24%, increasing from 15% in mild‐to‐moderate HF to 39% in severe HF. Patients with SDB had significantly higher levels of BNP and noradrenaline than those without SDB (mean (SD) BNP: 187 (119) versus 73 (98) pg mL−1, P = 0.02; noradrenaline: 309 (183) versus 225 (148) nmol/24 h, P = 0.05). There was no significant difference in reported sleepiness or in any domain of SF‐36, between groups with and without SDB (ESS: 7.8 (4.7) versus 7.5 (3.6), P = 0.87). In summary, in a general HF clinic population, the prevalence of SDB increased with the severity of HF. Patients with SDB had higher activation of a neurohumoral marker and more severe HF. Unlike obstructive sleep apnoea, SDB in HF had little discernible effect on sleepiness or quality of life as measured by standard subjective scales.
Random number generation during sleep deprivation: effects of caffeine on response maintenance and stereotypy
Authors: GOTTSELIG JULIE M. , ADAM MARTIN , RÉTEY JULIA V. , KHATAMI RAMIN , ACHERMANN PETER , LANDOLT HANS‐PETER
Published: February 2006

Neurophysiological and functional imaging studies have demonstrated that frontal regions of the brain are particularly responsive to homeostatic sleep pressure. Previous neuropsychological studies indicate that sleep deprivation causes impairments in prefrontal cortical function. Random number generation (RNG) is thought to provide a sensitive index of executive functions that rely on the prefrontal cortex. The present study tested the hypothesis that sleep deprivation would impair RNG and that caffeine would mitigate this impairment. Healthy young men (n = 21) participated in two 40‐h sleep deprivations 1 week apart. During each sleep deprivation period subjects received either caffeine or placebo according to a randomized, double‐blind cross‐over design, and they completed an oral RNG task at 3‐h intervals. Comparison of test sessions at analogous times of day revealed that sleep deprivation was associated with significant drops in the number of responses, a threefold increase in the percentage of rule violations, 59% greater response redundancy and a 20% increase in stereotypy of adjacent response pairs. Sleep deprivation did not consistently alter counting tendency. Caffeine ameliorated the decrease in the number of responses but did not mitigate other deficits in RNG that arose during sleep deprivation. These findings are consistent with prior reports of diminished vigilance and increased perseveration during extended wakefulness. They support the conclusion that caffeine preserves simple aspects of cognitive performance during sleep deprivation, whereas caffeine may not prevent detrimental effects of sleep deprivation on some complex cognitive functions.
Circulating adrenomedullin in obstructive sleep apnoea
Authors: SCHULZ RICHARD , FLÖTOTTO CHRISTIANE , JAHN ANDREAS , EISELE HANS JOACHIM , WEISSMANN NORBERT , SEEGER WERNER , ROSE FRANK
Published: February 2006

Adrenomedullin (AM) is a potent endothelial‐derived vasodilator secreted under the influence of various stimuli such as hypoxia, shear stress and cytokines. As all of these stimuli might be active under the conditions of obstructive sleep apnoea (OSA), we hypothesized that vascular AM production is increased in these patients. The study included 41 consecutive OSA patients and 28 control subjects without sleep‐disordered breathing who were recruited from a pool of patients hospitalized for other reasons. Both groups were matched for anthropometric and comorbid factors. In all patients, i.e. OSA and controls, peripheral venous blood samples were taken at 07:00 hours after diagnostic polysomnography. In subsets of OSA patients, this was repeated after two nights of continuous positive airway pressure (CPAP) therapy (n = 28) and after several months of constant CPAP use (n = 11). The controls and the untreated OSA patients did not have serial blood sampling. In all blood samples, plasma AM levels were measured by an enzyme immunoassay kit. At baseline, the OSA patients had markedly elevated AM concentrations when compared to the controls. There were no differences between normo‐ and hypertensive OSA patients. After two nights of CPAP therapy, AM levels significantly decreased. Patients on long‐term CPAP treatment showed complete normalization of plasma AM concentrations. In conclusion, this pilot study suggests that circulating AM is increased in untreated OSA irrespective of coexistent arterial hypertension and declines after CPAP therapy. AM upregulation might be considered as an adaptive mechanism to counteract the emergence of OSA‐related cardiovascular disease.
Characterizing sleep problems in persons with Alzheimer's disease and normal elderly
Authors: TRACTENBERG ROCHELLE E. , SINGER CLIFFORD M. , KAYE JEFFREY A.
Published: February 2006

We retrospectively analyzed sleep disturbance symptoms and estimated time in bed from the intake interviews of 399 healthy, non‐demented elderly (NDE) and 263 persons with a diagnosis of possible (n = 53) or probable (n = 210) Alzheimer's disease (AD). Our primary objective was to identify what symptoms might underlie an individual's perception of ‘sleep problems’ and to determine if these were consistent within, and across, our two cohorts. We stratified each cohort according to whether or not they (or their caregiver) indicated that they had a ‘sleep problem’, and compared the frequency and endorsement rates of each of 21 sleep disturbance symptoms across those who did or did not endorse ‘sleep problem’. For less than half of the symptoms in persons with AD, and a quarter of those in NDE, endorsement rates were significantly different depending on whether the reporter (or their sleep partner) did or did not report a sleep problem. Differences in mean frequency ratings between individuals reporting sleep problems relative to those not reporting were observed on 10 symptoms in both cohorts; six of these were the same symptom for both cohorts. When persons with subjective sleep problems in the AD and NDE cohorts were compared, only four of 21 symptoms were endorsed in one and not the other; two symptoms were significantly more frequent in one cohort than the other. Thus, within cohorts, the differences between persons with and without ‘sleep problems’ were relatively pronounced while the main differences in specific sleep‐related symptoms between AD and NDE were not. Observed between‐cohort differences appear to be driven by who is reporting, and the high prevalence of daytime sleeping in AD. Within‐cohort differences reflect a clear distinction between persons with and without sleep problems, regardless of the reporter.
The effect of sleepiness on performance monitoring: I know what I am doing, but do I care?
Authors: MURPHY TIMOTHY I. , RICHARD MARY , MASAKI HIROAKI , SEGALOWITZ SIDNEY J.
Published: February 2006

The behavioral, cognitive, and psychophysiological effects of extended wakefulness are well known. As time awake increases, errors become more common and are often attributed to lapses in attention. Such lapses can be reflected in the error‐related negativity (Ne/ERN), a negative electroencephalogram deflection occurring after errors and is thought to be related to error detection or response conflict. Following the Ne/ERN, a positive deflection (error positivity, Pe) is also observed and is thought to reflect further evaluation of the error. To elicit Ne/ERNs, the Eriksen Flanker Task was administered to 17 women (aged 19–45 years) at two levels of alertness (4 and 20 h awake). After extended wakefulness, participants reported being subjectively sleepier and performing worse, but showed no significant difference in subjective effort. Across alertness conditions, they reported a similar number of subjective errors which closely matched an objective analysis of the errors. The Ne/ERN was not significantly reduced by sleepiness in contrast to the Pe which was reduced. Behavioral slowing after errors was larger in the alert than in the sleepy condition. These results show that after 20 h of wakefulness, individuals are reacting to their errors. However, further evaluation of the error, and remediation of these errors may be impaired despite continued effort.
Subjective sleepiness, simulated driving performance and blink duration: examining individual differences
Authors: INGRE MICHAEL , ÅKERSTEDT TORBJÖRN , PETERS BJÖRN , ANUND ANNA , KECKLUND GÖRAN
Published: February 2006

The present study aimed to provide subject‐specific estimates of the relation between subjective sleepiness measured with the Karolinska Sleepiness Scale (KSS) and blink duration (BLINKD) and lane drifting calculated as the standard deviation of the lateral position (SDLAT) in a high‐fidelity moving base driving simulator. Five male and five female shift workers were recruited to participate in a 2‐h drive (08:00–10:00 hours) after a normal night sleep and after working a night shift. Subjective sleepiness was rated on the KSS in 5‐min intervals during the drive, electro‐occulogram (EOG) was measured continuously to calculate BLINKD, and SDLAT was collected from the simulator. A mixed model anova showed a significant (P < 0.001) effect of the KSS for both dependent variables. A test for a quadratic trend suggests a curvilinear effect with a steeper increase at high KSS levels for both SDLAT (P < 0.001) and BLINKD (P = 0.003). Large individual differences were observed for the intercept (P < 0.001), suggesting that subjects differed in their overall driving performance and blink duration independent of sleepiness levels. The results have implications for any application that needs prediction at the subject level (e.g. driver fatigue warning systems) as well as for research design and the interpretation of group average data.
Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience
Authors: Tillmann H. L. , Hadem J. , Leifeld L. , Zachou K. , Canbay A. , Eisenbach C. , Graziadei I. , Encke J. , Schmidt H. , Vogel W. , Schneider A. , Spengler U. , Gerken G. , Dalekos G. N. , Wedemeyer H. , Manns M. P.
Published: February 2006

Summary.  Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV‐DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.
Induction of early murine cytomegalovirus infection by different reporter gene‐associated recombinant viruses
Authors: Drebber U. , Haferkamp K. , Kern M. A. , Müller M. , Zur Hausen A. , Kasper H. U. , Odenthal M. , Dienes H. P.
Published: February 2006

Summary.  Murine cytomegalovirus (MCMV) has provided useful models for acute, chronic and latent CMV infection because of its similarities in structure and biology with human CMV. We report the induction of acute MCMV hepatitis with different bacterial artificial chromosome (BAC)‐cloned virus constructs [MCMV‐SEAP which includes the gene for secreted alkaline phosphatase (SEAP) under Rous sarcoma virus (RSV)‐promoter control, MCMV‐GFP which includes the gene for enhanced green fluorescent protein (eGFP) under HCMV‐ie promoter control, MCMV‐HBs includes the gene for hepatitis B surface antigen (HBsAg) under simian virus (SV)40‐promoter control and the DeltaMC95.21 virus in which the m152 gene was deleted and substituted by the reporter gene lacZ] in order to elucidate the histopathological changes together with different reporter‐gene products in the liver tissue and the effect of the deletion of a certain gene. All the virus constructs induced a similar mild acute hepatitis which had its climax from days 3 to 5 post‐infection in immunocompetent mice. In situ, the reporter‐gene products beta‐galactosidase and secreted alkaline phosphatase could be visualized in relation to the inflammatory changes. The composition of the invading cell populations did not change even in the absence of the m152 gene. Additionally discrete inflammatory changes were seen in kidney and serosa while the other organs were not involved. This model helps us understand the immunological and histopathological mechanisms of the CMV‐induced hepatitis, which plays an important role especially in the immunocompromised patient. The morphological changes can be analysed while the respective reporter gene product is expressed by the virus construct.
Clinical pathways for patients with newly diagnosed hepatitis C – What actually happens
Authors: Irving W. L. , Smith S. , Cater R. , Pugh S. , Neal K. R. , Coupland C. A. C. , Ryder S. D. , Thomson B. J. , Pringle M. , Bicknell M. , Hippisley‐Cox J.
Published: February 2006

Summary.  Management of hepatitis C virus (HCV)‐infected individuals requires referral to specialist care. To determine whether patients newly diagnosed as anti‐HCV positive are appropriately referred for further investigation and management, and if not, to determine why not. We studied patients tested for antibodies to HCV by Nottingham Public Health Laboratory in a 2‐year period (2000–2002). The progress of newly diagnosed anti‐HCV positive patients into specialist clinics for further management was documented. For patients not referred for specialist care, a questionnaire was sent to the clinician requesting the initial anti‐HCV test, to identify reasons for nonreferral. Eleven thousand one hundred and seventy‐seven patients were tested for anti‐HCV. Two hundred and fifty‐six (2.3%) were newly diagnosed as being anti‐HCV positive. Two per cent of samples sent from primary care were anti‐HCV positive, compared to 18.8, 18.9 and 1.3% sent from prison, drug and alcohol units, and secondary care, respectively. About 64.3% of positive patients diagnosed in primary care were referred to specialist care, compared to 18.4, 42.4 and 62.6% of patients diagnosed in the other three settings. One hundred and twenty‐five (49%) newly diagnosed patients were referred appropriately for further management. 68 of these attended clinic, 45 underwent liver biopsy and 26 (10%) began treatment. One hundred and thirty‐one patients (51%) were not referred. In 54 cases, there was no evidence that the anti‐HCV positive result reached the patient. In 15, referral was considered but rejected, and 20 patients were referred to non‐HCV‐specialists (their general practitioners or to genito‐urinary medicine). Hence less than 50% of newly diagnosed anti‐HCV positive patients are referred to an appropriate clinic for further investigation and management. Reasons for this are multifarious and complex, reflecting both systems failure and patient choice. Unless these are understood and addressed, the Department of Health Hepatitis C Strategy (2002) and Action Plan for England (2004) will fail to achieve their intended objectives.
The role of thyroid autoantibodies in the development of thyroid dysfunction in Taiwanese chronic hepatitis C patients with interferon‐alpha and ribavirin combination therapy
Authors: Huang J‐F. , Chuang W‐L. , Dai C‐Y. , Chen S‐C. , Lin Z‐Y. , Lee L‐P. , Lee P‐L. , Wang L‐Y. , Hsieh M‐Y. , Chang W‐Y. , Yu M‐L.
Published: February 2006

Summary.  To investigate the role of thyroid autoantibodies in the development of thyroid dysfunction among chronic hepatitis C (CHC) patients receiving interferon‐alpha (IFN‐α) plus ribavirin (RBV) combination therapy, 95 Taiwanese naïve patients with baseline euthyroidism were enrolled. They were treated with IFN‐α2b, 6 million units thrice weekly, plus RBV 1000–1200 mg daily for 24 weeks. Thyroid function, anti‐thyroglobulin and antiperoxidase autoantibodies were tested at enrolment (M0), at the end‐of‐treatment (M6) and 6 months after end‐of‐treatment (M12). The percentages of thyroid autoantibodies were 8.4%, 11.6% and 9.5%, at M0, M6 and M12 respectively. Fourteen (14.7%) patients developed thyroid dysfunction at M6 or M12. Thyroid dysfunction occurred during treatment in five (62.5%) of the eight patients with baseline thyroid autoantibodies, which was significantly higher than nine (10.3%) of 87 patients without baseline thyroid autoantibodies (P = 0.0001). Among 14 patients who developed thyroid dysfunction, four (80.0%) of five patients with baseline thyroid autoantibodies recovered at M12, in contrast to two (25%) of eight without baseline thyroid autoantibodies recovered at M12 (P < 0.05). In conclusion, thyroid autoantibodies, either occurred before or during IFN‐α plus RBV combination therapy, carry a high prediction of subsequent thyroid dysfunction. There also exists difference in the clinical manifestations of thyroid dysfunction in CHC patients treated with combination therapy.
Low serum tryptophan levels, reduced macrophage IDO activity and high frequency of psychopathology in HCV patients
Authors: Cozzi A. , Zignego A. L. , Carpendo R. , Biagiotti T. , Aldinucci A. , Monti M. , Giannini C. , Rosselli M. , Laffi G. , Moroni F.
Published: February 2006

Summary.  Indoleamine 2,3‐dioxygenase (IDO), a key enzyme of tryptophan (TRP) metabolism, is induced in various tissues of patients with bacterial and viral infection or with neoplastic diseases. This induction is considered the main cause of the decreased serum TRP levels, the reduced brain serotonin synthesis and the occurrence of psychopathological disorders often detected in patients with chronic infections or different forms of cancer. We studied 89 subjects including: (a) 39 patients with chronic hepatitis C virus (HCV) infection and mild liver damage (b) 40 healthy controls, and (c) 10 patients with chronic hepatitis B virus (HBV) infection. We measured serum TRP and kynurenine levels and IDO activity in macrophages. Furthermore, each patient had an accurate psychopathological evaluation. HCV‐infected patients had lower (−28%) serum TRP concentrations than healthy volunteers or HBV‐infected patients with comparable liver damage. Depression and anxiety symptoms were particularly common in HCV patients. Unexpectedly, serum kynurenine levels and IDO activity in cultured macrophages (under both basal or stimulated conditions) were lower in HCV patients than in controls. Our study shows that HCV patients have reduced serum TRP levels and confirms that they frequently suffer from anxiety and depression‐related symptoms. The reduced IDO activity found in the macrophages of these patients suggest that HCV infection may hamper macrophage functions.
Long‐term effect of interferon alpha‐2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis
Authors: Hung C.‐H. , Lee C.‐M. , Lu S.‐N. , Wang J.‐H. , Hu T.‐H. , Tung H.‐D. , Chen C.‐H. , Chen W.‐J. , Changchien C.‐S.
Published: February 2006

Summary.  We assessed the efficacy of interferon (IFN) alpha‐2b plus ribavirin therapy in patients with hepatitis C virus (HCV)‐related cirrhosis, and elucidated the risk factors for the development of hepatocellular carcinoma (HCC) to determine whether these therapies might reduce the incidence of HCC. One hundred and thirty‐two HCV‐cirrhotic patients receiving IFN alpha‐2b (3 or 5 MU thrice weekly) and oral ribavirin (1000–1200 mg/day) for 24 or 48 weeks were analysed. Cumulative incidence of HCC was estimated by the Kaplan–Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log‐rank test and by multivariate Cox's regression analysis. A total of 116 patients completed the treatment and 73 (55%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that nongenotype 1b (P < 0.001) and low viral load (P = 0.018) were independent variables of SVR. During a median follow‐up period of 37 (12–63) months, HCC developed in 11 patients with non‐SVR and five with SVR (P = 0.0178), whereas there was no difference between those with transient biochemical response and nonresponse (P = 0.5970). The Kaplan–Meier method also showed that old age (≥60 years) (P = 0.0034) and genotype 1b (P = 0.0104) were associated with HCC occurrence. Using Cox's regression analysis, non‐SVR (odds ratio = 3.521, P = 0.036), male (odds ratio = 6.269, P = 0.011) and old age (odds ratio = 3.076, P = 0.049) were independent significant risk factors contributing to HCC development. Our results suggest that achieving SVR by IFN alpha‐2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV‐related cirrhosis.
Insulin resistance is not associated with liver fibrosis progression in HIV/hepatitis C virus‐coinfected patients
Authors: Merchante N. , Macías J. , Ramayo E. , Vergara S. , García‐García J. A. , Mira J. A. , Corzo J. E. , Gómez‐Mateos J. M. , Lozano F. , Pineda J. A.
Published: February 2006

Summary.  Insulin resistance (IR) is a common condition in chronic hepatitis C. Recent studies have reported that IR is associated with liver fibrosis progression in these patients. However, there is no information available on this issue in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)‐coinfected patients. For these reasons, we investigate the relationship between IR and liver fibrosis in patients with HIV and HCV infections. This was a cross‐sectional study where patients from an Infectious Diseases Unit with HIV/HCV coinfection who underwent a liver biopsy, with available frozen sera samples at the time of biopsy and a known or estimated date of infection were included. IR was determined by the homeostasis model assessment (HOMA‐IR) method. The relationship between histological findings and several variables, including HOMA‐IR values, was examined. Seventy‐nine patients fulfilled the inclusion criteria. Age at HCV infection >21 years was the only variable independently associated with advanced liver fibrosis (stages F3 and F4) [adjusted odds ratio (AOR) 4.15; 95% confidence interval (CI) 1.5–11.3]. The variables associated with a fibrosis progression rate above the median were age at HCV infection >21 years (AOR 6.41; 95% CI 2.16–27.96) and previous exposure to nevirapine (AOR 8.9; 95% CI 2.01–39.36). There was no association between HOMA‐IR values and the presence of advanced fibrosis or a faster fibrosis progression. Thus IR is not associated with liver damage or fibrosis progression in HIV/HCV‐coinfected individuals.