bluuebunny/crossref_metadata_2025 huggingface dataset:
Deactivation of murine alveolar macrophages by peroxisome proliferator-activated receptor-γ ligands
Authors: Reddy Raju C. , Keshamouni Venkateshwar G. , Jaigirdar Shamsul H. , Zeng Xianying , Leff Todd , Thannickal Victor J. , Standiford Theodore J.
Published: February 2004

Peroxisome proliferator-activated receptor-γ (PPAR-γ), a member of the nuclear hormone receptor family of ligand-dependent transcription factors, is a critical regulator of adipocyte differentiation and glucose metabolism. The expression, regulation, and functional significance of PPAR-γ in alveolar macrophages (AMs), the predominant resident immune effector cell within the alveolus, have not been previously examined. In this study, we show that, in contrast to peritoneal macrophages, resident murine AMs constitutively express high levels of PPAR-γ. Expression was primarily located in the nucleus by immunofluorescence staining. Quantitative real-time RT-PCR demonstrated that the predominant isoform was PPAR-γ2. Expression of PPAR-γ was induced by the anti-inflammatory cytokine IL-4. Treatment of murine AMs with PPAR-γ ligands suppresses PMA-stimulated oxidative burst activity and LPS + IFN-γ-mediated expression of inducible nitric oxide synthase. In addition, LPS-induced IL-12 mRNA and protein expression was inhibited by PPAR-γ ligands. These results support an important immunomodulatory role for PPAR-γ in AM responses.
Nordexfenfluramine causes more severe pulmonary vasoconstriction than dexfenfluramine
Authors: Hong Zhigang , Olschewski Andrea , Reeve Helen L. , Nelson Daniel P. , Hong Fangxiao , Weir E. Kenneth
Published: February 2004

The anorectic agent dexfenfluramine (dex) causes the development of primary pulmonary hypertension in susceptible patients by an unknown mechanism. We compared the effects of dex with those of its major metabolite, nordexfenfluamine (nordex), in the isolated perfused rat lung and in isolated rings of resistance pulmonary arteries. Nordex caused a dose-dependent and more intense vasoconstriction, which can be inhibited by the nonspecific 5-hydroxytryptamine type 2 (5-HT2) blocker ketanserin. Similarly a rise in cytosolic calcium concentration ([Ca2+]i) in dispersed pulmonary artery smooth muscle cells (PASMCs) induced by nordex could be prevented by ketanserin. Unlike prior observations with dex, nordex did not inhibit K+current or cause depolarization in PASMCs. Removal of Ca2+from the tissue bath or addition of nifedipine (1 μM) reduced ring contraction to nordex by 60 ± 9 and 63 ± 4%, respectively. The addition of 2-aminoethoxydiphenyl borate (2-APB), a blocker of store-operated channels and the inositol 1,4,5-trisphosphate receptor, caused a dose-dependent decrease in the ring contraction elicited by nordex. The combination of 2-APB (10 μM) and nifedipine (1 μM) completely ablated the nordex contraction. Likewise the release of Ca2+from the sarcoplasmic reticulum by cyclopiazonic acid markedly reduced the nordex contraction while leaving the KCl contraction unchanged. We conclude that nordex may be responsible for much of the vasoconstriction stimulated by dex, through the activation of 5-HT2receptors and that the [Ca2+]iincrease in rat PASMCs caused by dex/nordex is due to both influx of extracellular Ca2+and release of Ca2+from the sarcoplasmic reticulum.
Short-term fluoxetine treatment enhances baroreflex control of sympathetic nervous system activity after hindlimb unloading
Authors: Moffitt Julia A. , Johnson Alan Kim
Published: February 2004

Data in humans indicate that individuals with orthostatic hypotension that are refractory to other traditional forms of therapy are responsive to selective serotonin reuptake inhibitor (SSRI) treatment. We tested the hypothesis that SSRI administration would help correct the attenuated baroreflex control of sympathetic nervous system activity in the hindlimb-unloaded (HU) rat model of cardiovascular deconditioning. An initial study was conducted to determine the time course of effects of fluoxetine (Flu) administration on baroreflex control of lumbar sympathetic nerve activity (LSNA) in conscious, chronically instrumented rats. Animals received either vehicle (Veh, sterile water) or 10 mg/kg Flu for 1, 4, or 16 days of treatment. Data indicate that while 1-day and 16-day Flu administration did not affect baroreflex function, baroreflex control of LSNA was enhanced after 4-day (short term) Flu administration. HU rats were then treated with Flu for 4 days and compared with HU rats receiving Veh and to casted control rats maintained in the normal posture that received either Veh or short-term Flu treatment. Similar to pilot data, short-term Flu treatment enhanced baroreflex control of LSNA in both HU rats and control rats. These data taken together indicate that baroreflex control of sympathetic nervous system activity is a possible mechanism responsible for the successful treatment of orthostatic intolerance with Flu.
Docosahexaenoic acid affects insulin deficiency- and insulin resistance-induced alterations in cardiac mitochondria
Authors: Ovide-Bordeaux Stéphanie , Grynberg Alain
Published: February 2004

The effect of docosahexaenoic acid (DHA) intake on cardiac mitochondrial function was evaluated in permeabilized fibers in insulin deficiency and insulin resistance in rats. The insulin-deficient state was obtained by streptozotocin injection 2 mo before investigations. Insulin resistance was obtained by feeding a 62% fructose diet for 3 mo. DHA was incorporated in the diet to modify the fatty acid composition of cardiac membranes, including mitochondria. Insulin deficiency decreased mitochondrial creatine kinase (mi-CK) activity and mitochondrial sensitivity to ADP. DHA intake prevented these alterations. Moreover, the insulin-deficient state significantly decreased n-3 polyunsaturated fatty acids (PUFA) and slightly increased n-6 PUFA in both cardiac and mitochondrial membranes, inducing a significant increase in the n-6-to-n-3 ratio. DHA intake maintained high myocardial and mitochondrial DHA content. Insulin deficiency also decreased glutamate- and palmitoylcarnitine-supported mitochondrial respiration, but DHA intake did not prevent these effects. In contrast, insulin resistance did not affect mi-CK activity or sensitivity to ADP. However, insulin resistance influenced the myocardial fatty acid composition with decreased n-6 and n-3 PUFA contents and increased monounsaturated fatty acid content. Only slight alterations were observed in mitochondrial fatty acid composition, and they were corrected by DHA intake. Moreover, insulin resistance decreased the glutamate-supported respiration, and DHA intake did not influence this effect. In conclusion, the impairment of cardiac mitochondrial function was more pronounced in the insulin-deficient state than in insulin resistance. The modification of fatty acid composition of cardiac and mitochondrial membranes by DHA partially prevented the mitochondrial alterations induced in the two models.
Osmotic regulation of estrogen receptor-β expression in magnocellular vasopressin neurons requires lamina terminalis
Authors: Somponpun Suwit J. , Johnson Alan Kim , Beltz Terry , Sladek Celia D.
Published: February 2004

Estrogen receptor-β (ER-β) expression in rat magnocellular vasopressin (VP) neurons of the supraoptic and paraventricular nuclei (SON and PVN, respectively) becomes undetectable after 72 h of 2% NaCl consumption. To test the hypothesis that osmosensitive mechanisms that originate in the region of the organum vasculosum lamina terminalis (OVLT) control ER-β expression in the SON and PVN, animals were water deprived after electrolytic lesions were performed on the area anterior to the ventral third ventricle (AV3V). Such lesions prevent osmotic stimulation of VP release. Four weeks after surgery, male rats [lesioned ( n = 16) or sham ( n = 14)] were water deprived for 48 h or allowed water ad libitum. Water deprivation eliminated ER-β-immunoreactivity (-ir) in SON and magnocellular PVN of sham-lesioned animals. Fos-ir was evident in these neurons, and plasma osmolality (Posm) and hematocrit (Ht) were significantly elevated compared with the sham-hydrated rats (Posm, 304 ± 1 vs. 318 ± 2 mosmol/kgH2O; P < 0.001; Ht, 49.6 ± 0.6 vs. 55.0 ± 0.9%; P < 0.001). ER-β expression was comparable in sham-hydrated, AV3V-hydrated, and 6 of 8 AV3V-dehydrated rats despite significant increases in Posm in both groups (AV3V hydrated, 312 ± 2; AV3V dehydrated, 380 ± 10 mosmol/kgH2O; P < 0.001). OVLT was not ablated in the AV3V-dehydrated rats in which ER-β was depleted. Fos-ir was low or undetectable in SON in the AV3V-hydrated animals despite elevated Posm values. In AV3V-dehydrated rats, Fos-ir was significantly less than in sham-dehydrated animals but was significantly increased compared with the sham-hydrated group. This could reflect activation by nonosmotic parameters that do not inhibit ER-β expression. These data support the hypothesis that inhibition of ER-β expression in the SON by osmotic stimulation is mediated by osmoreceptive neurons in the lamina terminalis.
Development of the nocturnal sleep electroencephalogram in human infants
Authors: Jenni Oskar G. , Borbély Alexander A. , Achermann Peter
Published: February 2004

The development of nocturnal sleep and the sleep electroencephalogram (EEG) was investigated in a longitudinal study during infancy. All-night polysomnographic recordings were obtained at home at 2 wk and at 2, 4, 6, and 9 mo after birth (analysis of 7 infants). Total sleep time and the percentage of quiet sleep or non-rapid eye movement sleep (QS/NREMS) increased with age, whereas the percentage of active sleep or rapid eye movement sleep (AS/REMS) decreased. Spectral power of the sleep EEG was higher in QS/NREMS than in AS/REMS over a large part of the 0.75- to 25-Hz frequency range. In both QS/NREMS and AS/REMS, EEG power increased with age in the frequency range <10 Hz and >17 Hz. The largest rise occurred between 2 and 6 mo. A salient feature of the QS/NREMS spectrum was the emergence of a peak in the sigma band (12-14 Hz) at 2 mo that corresponded to the appearance of sleep spindles. Between 2 and 9 mo, low-frequency delta activity (0.75-1.75 Hz) showed an alternating pattern with a high level occurring in every other QS/NREMS episode. At 6 mo, sigma activity showed a similar pattern. In contrast, theta activity (6.5-9 Hz) exhibited a monotonic decline over consecutive QS/NREMS episodes, a trend that at 9 mo could be closely approximated by an exponential function. The results suggest that 1) EEG markers of sleep homeostasis appear in the first postnatal months, and 2) sleep homeostasis goes through a period of maturation. Theta activity and not delta activity seems to reflect the dissipation of sleep propensity during infancy.
Role of the medullary lateral tegmental field in reflex-mediated sympathoexcitation in cats
Authors: Orer Hakan S. , Gebber Gerard L. , Phillips Shaun W. , Barman Susan M.
Published: February 2004

We tested the hypothesis that blockade of N-methyl-d-aspartate (NMDA) and non-NMDA receptors on medullary lateral tegmental field (LTF) neurons would reduce the sympathoexcitatory responses elicited by electrical stimulation of vagal, trigeminal, and sciatic afferents, posterior hypothalamus, and midbrain periaqueductal gray as well as by activation of arterial chemoreceptors with intravenous NaCN. Bilateral microinjection of a non-NMDA receptor antagonist into LTF of urethane-anesthetized cats significantly decreased vagal afferent-evoked excitatory responses in inferior cardiac and vertebral nerves to 29 ± 8 and 24 ± 6% of control ( n = 7), respectively. Likewise, blockade of non-NMDA receptors significantly reduced chemoreceptor reflex-induced increases in inferior cardiac (from 210 ± 22 to 129 ± 13% of control; n = 4) and vertebral nerves (from 253 ± 41 to 154 ± 20% of control; n = 7) and mean arterial pressure (from 39 ± 7 to 21 ± 5 mmHg; n = 8). Microinjection of muscimol, but not an NMDA receptor antagonist, caused similar attenuation of these excitatory responses. Sympathoexcitatory responses to the other stimuli were not attenuated by microinjection of a non-NMDA receptor antagonist or muscimol into LTF. In fact, excitatory responses elicited by stimulation of trigeminal, and in some cases sciatic, afferents were enhanced. These data reveal two new roles for the LTF in control of sympathetic nerve activity in cats. One, LTF neurons are involved in mediating sympathoexcitation elicited by activation of vagal afferents and arterial chemoreceptors, primarily via activation of non-NMDA receptors. Two, non-NMDA receptor-mediated activation of other LTF neurons tonically suppresses transmission in trigeminal-sympathetic and sciatic-sympathetic reflex pathways.
LurcherMice Exhibit Potentiation of GABAA-Receptor–Mediated Conductance in Cerebellar Nuclei Neurons in Close Temporal Relationship to Purkinje Cell Death
Authors: Linnemann C. , Sultan F. , Pedroarena C. M. , Schwarz C. , Thier P.
Published: February 2004

In heterozygous Lurcher mice ( Lc/+), the Purkinje cells (PCs) degenerate almost totally during postnatal development. On the other hand, their projection target, the deep cerebellar nuclei (DCN), shows few signs of degeneration and seems to play an important role in maintaining a residual cerebellar function in Lc/+. We asked whether the DCN in Lc/+ develop cellular adaptations allowing them to cope with the loss of GABAergic PC input. Using whole-cell patch-clamp recordings, we measured inhibitory postsynaptic currents from DCN of Lc/+ and wild-type mice (WT). In experiments on phenotypically striking Lc/+ studied well after the onset of the PC degeneration, we found enlarged average synaptic conductances ( gsyn) compared with WT. We next investigated postnatal mice before and after the onset of PC death. In younger animals ≤ postnatal day (p) 13, no difference was found in gsynbetween the two groups. At p14, gsynin Lc/+ showed an increase, while those in WT stayed on the level found in younger animals. A peak-scaled nonstationary fluctuation analysis suggests that an increase in the average number of channels open at peak is the basis for the change in gsyn. The changes in gsyn, suitable to increase the efficacy of GABAergic transmission, occur in close temporal relationship to PC death and, thus, may reflect a functional adaptation to the loss of the DCN's main GABAergic afferents.
Conjugate Adaptation of Saccadic Gain in Non-Human Primates With Strabismus
Authors: Das Vallabh E. , Ono Seiji , Tusa Ronald J. , Mustari Michael J.
Published: February 2004

In this study, we have used the double-step paradigm to test saccadic gain adaptation during monocular viewing in one normal monkey, two monkeys with exotropia, and one monkey with esotropia. In this paradigm, the target for the saccade is displaced during the saccade, resulting in a consistent visual error. Studies in normal humans and monkeys have shown that the brain responds to this consistent visual error by gradually changing saccade gain. Using this technique, we were able to elicit adaptation in both the viewing eye and the nonviewing eye in the normal monkey and in monkeys with strabismus. The rate of adaptation was not significantly different in the viewing and nonviewing eyes in the normal and strabismic monkeys. The magnitude of adaptation as calculated by a percentage change in gain was also not significantly different in the viewing and the nonviewing eyes in the normal and strabismic monkeys. Our data show that animals with strabismus retain the ability to elicit a conjugate adaptation of saccades using this mechanism. We also suggest that the double-step paradigm elicits a conjugate adaptation of saccades whether the animal is viewing monocularly (our studies) or binocularly (data published in literature).
Microstimulation in the Region of the Human Thalamic Principal Somatic Sensory Nucleus Evokes Sensations Like Those of Mechanical Stimulation and Movement
Authors: Ohara Shinji , Weiss Nirit , Lenz Fred A.
Published: February 2004

We explored the region of human thalamic somatic sensory nucleus (ventral caudal, Vc), corresponding to monkey ventral posterior (VP), with threshold microstimulation (TMIS) during stereotactic procedures for the treatment of tremor. Of 122 sites in 116 patients (124 thalami) where mechanical (touch, pressure, and sharp) or movement [movement through the body (movement) and vibration] sensations were evoked, 72 sites were found in the core or in adjacent regions, posterior-inferior (33), inferior (4), and posterior to the core (13). Sites where TMIS evoked touch were less frequently found in the core than those where movement or pressure sensations were evoked. Pressure was more commonly ( P < 0.05) evoked than vibration at sites where cells had intraoral receptive fields (RFs). Touch and vibration were more commonly ( P < 0.05) evoked than pressure at sites where cells had facial RFs, consistent with the relative density of rapidly adapting (RA) receptors in the mouth and face. Sites described as deep and movement were found superior and anterior in the core, consistent with the location of cells responding to stimulation of muscle afferents. At 72 of 122 sites, TMIS evoked the same sensation at two or more sites in the same plane. Of these sites, 58 are adjacent to each other, in a cluster, consistent with studies of the localization of cells responding to different modalities. These results demonstrate that mechanical and movement sensations can be evoked by stimulation in the region of Vc. The characteristics of these sites suggest that the sensations are evoked by stimulation of pathways specific to cutaneous and deep mechanoreceptors.
Endogenous Zinc Inhibits GABAAReceptors in a Hippocampal Pathway
Authors: Ruiz Arnaud , Walker Matthew C. , Fabian-Fine Ruth , Kullmann Dimitri M.
Published: February 2004

Depending on their subunit composition, GABAAreceptors can be highly sensitive to Zn2+. Although a pathological role for Zn2+-mediated inhibition of GABAAreceptors has been postulated, no direct evidence exists that endogenous Zn2+can modulate GABAergic signaling in the brain. A possible explanation is that Zn2+is mainly localized to a subset of glutamatergic synapses. Hippocampal mossy fibers are unusual in that they are glutamatergic but have also been reported to contain GABA and Zn2+. Here, we show, using combined Timm's method and post-embedding immunogold, that the same mossy fiber varicosities can contain both GABA and Zn2+. Chelating Zn2+with either calcium-saturated EDTA or N,N,N′ ,N′-tetrakis (2-pyridylmethyl)ethylenediamine had no effect on stratum-radiatum-evoked inhibitory postsynaptic currents (IPSCs), but enhanced IPSCs evoked by stimuli designed to recruit dentate granule cells. We also show that IPSCs recorded in CA3 pyramidal neurons in acute hippocampal slices are depressed by exogenous Zn2+. This depression was of similar amplitude whether the IPSCs were evoked by stimulation in s. radiatum (to recruit local interneurons) or in the s. granulosum of the dentate gyrus (to recruit mossy fibers). These results show for the first time that GABAergic IPSCs can be modulated by endogenous Zn2+and are consistent with GABA release at Zn2+-containing mossy fiber synapses.
Short Duty Cycle Destabilizes a Half-Center Oscillator, But Gap Junctions Can Restabilize the Anti-Phase Pattern
Authors: Bem Tiaza , Rinzel John
Published: February 2004

Mutually inhibitory pacemaker neurons with duty cycle close to 50% operate as a half-center oscillator (anti-phase coordination, i.e., 180° out of phase), even in the presence of weak to modest gap junctional coupling. For electrical coupling strength above a critical value synchronization occurs. But, as shown here with modeling studies, the effects of electrical coupling depend critically on a cell's duty cycle. Instead of oscillating either in-phase or anti-phase, model cells with short duty cycle express additional rhythmic patterns, and different transitions between them, depending on electrical coupling strength. For weak or no electrical coupling, cells do not oscillate in anti-phase but instead exhibit almost in-phase activity. Strengthening this weak coupling leads to stable anti-phase activity. With yet stronger electrical coupling stable inphase (synchrony) emerges but it coexists with the anti-phase pattern. Thus the network shows bistability for an intermediate range of coupling strength. For sufficiently strong electrical coupling synchrony is the network's only attracting rhythmic state. Our results, numerical and analytical (phase plane analysis), are based on a minimal but biophysically motivated pacemaker model for the slowly oscillating envelope of bursting neurons. However, illustrations for an Hodgkin–Huxley model suggest that some of our results for short duty cycle may extend to patterning of repetitive spikes. In particular, electrical coupling of intermediate strength may promote anti-phase activity and provide bistability of anti-phase and in-phase spiking.
Rapid Temporal Modulation of Synchrony by Competition in Cortical Interneuron Networks
Authors: Tiesinga P.H.E. , Sejnowski T. J.
Published: February 2004

The synchrony of neurons in extrastriate visual cortex is modulated by selective attention even when there are only small changes in firing rate (Fries, Reynolds, Rorie, & Desimone, 2001). We used Hodgkin-Huxley type models of cortical neurons to investigate the mechanism by which the degree of synchrony can be modulated independently of changes in firing rates.

The synchrony of local networks of model cortical interneurons interacting through GABAA synapses was modulated on a fast timescale by selectively activating a fraction of the interneurons. The activated interneurons became rapidly synchronized and suppressed the activity of the other neurons in the network but only if the network was in a restricted range of balanced synaptic background activity. During stronger background activity, the network did not synchronize, and for weaker background activity, the network synchronized but did not return to an asynchronous state after synchronizing. The inhibitory output of the network blocked the activity of pyramidal neurons during asynchronous network activity, and during synchronous network activity, it enhanced the impact of the stimulus-related activity of pyramidal cells on receiving cortical areas (Salinas & Sejnowski, 2001). Synchrony by competition provides a mechanism for controlling synchrony with minor alterations in rate, which could be useful for information processing.

Because traditional methods such as cross-correlation and the spike field coherence require several hundred milliseconds of recordings and cannot measure rapid changes in the degree of synchrony, we introduced a new method to detect rapid changes in the degree of coincidence and precision of spike timing.
One-Bit-Matching Conjecture for Independent Component Analysis
Authors: Liu Zhi-Yong , Chiu Kai-Chun , Xu Lei
Published: February 2004

The one-bit-matching conjecture for independent component analysis (ICA) could be understood from different perspectives but is basically stated as “all the sources can be separated as long as there is a one-toone same-sign-correspondence between the kurtosis signs of all source probability density functions (pdf's) and the kurtosis signs of all model pdf's” (Xu, Cheung, & Amari, 1998a). This conjecture has been widely believed in the ICA community and implicitly supported by many ICA studies, such as the Extended Infomax (Lee, Girolami, & Sejnowski, 1999) and the soft switching algorithm (Welling & Weber, 2001). However, there is no mathematical proof to confirm the conjecture theoretically. In this article, only skewness and kurtosis are considered, and such a mathematical proof is given under the assumption that the skewness of the model densities vanishes. Moreover, empirical experiments are demonstrated on the robustness of the conjecture as the vanishing skewness assumption breaks. As a by-product, we also show that the kurtosis maximization criterion (Moreau & Macchi, 1996) is actually a special case of the minimum mutual information criterion for ICA.
Systematic status of Campydora Cobb, 1920 (Nematoda: Campydorina)
Authors: Mullin Peter , Harris Timothy , Powers Thomas
Published: February 2004

The systematic position of Campydora Cobb, 1920, which possesses many unique morphological features, especially in pharyngeal structure and stomatal armature, has long been a matter of uncertainty with the 'position of the Campydorinae' (containing only Campydora) being questionable. A review of the morphology of C. demonstrans, the only nominal species of Campydora concluded that the species warranted placement as the sole member of a monotypic suborder, Campydorina, in the order Dorylaimida. Others placed Campydorina in the order Enoplida. We conducted phylogenetic analyses, using 18s small subunit ribosomal DNA sequences generated from a number of taxa in the subclasses Enoplia and Dorylaimia, to evaluate these competing hypotheses. Although precise taxonomic placement of the genus Campydora and the identity of its closest living relatives is in need of further investigation, our analyses, under maximum parsimony, distance, and maximum likelihood criteria, unambiguously indicate that Campydora shares a common, more recent, ancestry with genera such as Alaimus, Pontonema, Tripyla and Ironus (Enoplida), rather than with any members of Dorylaimida, Mononchida or Triplonchida.
Intraspecific variation in RFLP patterns and morphological studies on Steinernema feltiae and S. kraussei (Rhabditida: Steinernematidae) from Hokkaido, Japan
Authors: Yoshida Mutsuhiro
Published: February 2004

Steinernema feltiae and S. kraussei were isolated from Hokkaido, Japan. This is the first record of S. kraussei and the first definitive record of S. feltiae from Japan. The morphological variation of the infective juveniles and the first generation males of Japanese isolates of both species are reported. Intraspecific variation in the PCR-RFLP analysis of the ITS region of ribosomal DNA was observed in both species. The Japanese isolates of S. feltiae showed different RFLP patterns from European isolates with Dde I and Hinf I restriction digests. The Japanese isolate of S. kraussei also showed an RFLP variation from the UK and Russian isolates upon Dde I restriction digestion. Moreover, in each isolate of S. kraussei, some intra-population variations were observed with some restriction digestions. The intraspecific variation in the ITS region of the rDNA could be used as a molecular marker to distinguish the Japanese isolates from European isolates of S. feltiae if the latter was introduced as a biological insecticide.
Bias in retrospective studies of trends in asthma incidence
Authors: Brogger J. , Eagan T. , Eide G.E. , Bakke P. , Gulsvik A.
Published: February 2004

There is evidence for an increase in adult asthma prevalence. Several retrospective studies have shown an increase in asthma incidence by year of birth, consistent with an increasing trend in asthma incidence.

The validity of this retrospective approach is unknown. Retrospective and prospective asthma incidence by year of birth were compared in the same community, during the same time period, from two independent studies; a cohort study and a cross-sectional study in Western Norway. In the prospective study, subjects without asthma were followed from 1985–1996/1997. In the retrospective study in 1998, subjects reported the age at which the disease started. Analyses of incident asthma in the period 1985–1996 were compared between the studies.

The retrospective analysis showed a large increase in asthma incidence by year of birth, with an odds ratio (OR) of 2.9 comparing those born in 1969 with those born in 1927. The prospective study showed the opposite, with an OR of 0.2 comparing those born in 1969 with those born in 1927. There was only a 20% difference in the cumulative incidence of asthma.

To conclude, retrospective estimates of trends in asthma incidence are likely to be severely biased by differential recall.
Unlicensed and off-label prescription of respiratory drugs to children
Authors: 't Jong G.W. , Eland I.A. , Sturkenboom M.C.J.M. , van den Anker J.N. , Stricker B.H.C.
Published: February 2004

Many respiratory drugs are not available in formulations suitable for infants and toddlers. Efficacy and safety research is mostly restricted to older children. However, respiratory drugs are frequently used in children for common diseases like asthma, upper and lower respiratory tract infections, rhinitis and sinusitis. The unlicensed and off-label use of respiratory drugs in children were studied.

A population-based cohort study was conducted by using the computerised medical records in the Integrated Primary Care Information project. The study population comprised a random sample from all children aged 0–16 yrs who were registered with a general practitioner in 1998. All prescriptions for respiratory drugs during the study period were classified according to their licensing and off-label status.

The study population comprised 13,426 patients (51.7% male, median age 8.7 yrs), of whom 2,502 (19%) received 5,253 prescriptions for respiratory drugs in 1998. A total of 3,306 (62.9%) prescriptions concerned licensed drugs. Of the remaining 1,947 prescriptions (37.1%), 882 (16.8%) were unlicensed for use in children, and 1,065 (20.3%) were prescribed off-label. The 1‐yr cumulative risk of receiving an unlicensed or off-label prescription was 45% among children with at least one prescription for a respiratory drug.

This population-based study showed that a large proportion of respiratory drugs prescribed by the general practitioner are unlicensed for use in children, or licensed but prescribed in an off-label manner. Results have to be interpreted with caution because they may unjustly suggest inaccurate prescribing, whereas it may be difficult to treat children with respiratory symptoms and diseases, because for many respiratory drugs paediatric data on safety and efficacy are insufficient. These findings underline the importance of research on suitable formulations, dosages and efficacy of respiratory drugs in children.
Relationship between quality of life and clinical status in asthma: a factor analysis
Authors: Juniper E.F. , Wisniewski M.E. , Cox F.M. , Emmett A.H. , Nielsen K.E. , O'Byrne P.M.
Published: February 2004

Many studies have shown that correlation between clinical asthma status and asthma-specific quality of life is only weak to moderate. However, this relationship has never been explored to determine whether the weakness is due to noise of measurement or whether quality of life is a distinct component of asthma health status.

With a database from three clinical trials (n=763), factor analysis was used to explore the relationships between quality of life, measured by the Asthma Quality of Life Questionnaire (AQLQ), and conventional measures of asthma clinical status (symptoms, airway calibre and rescue β2‐agonist use).

The analysis revealed that although patients with severe, poorly controlled asthma tend to have worse quality of life than milder, well-controlled patients, overall asthma health status has four components (factors): asthma-specific quality of life; airway calibre; daytime symptoms and daytime β2‐agonist use, and night-time symptoms and night-time β2‐agonist use.

The clean loading of all 21 outcomes onto four distinct and clinically identifiable factors suggests that, although some weakness of correlation between clinical indices and quality of life may be due to noise of measurement, it is mainly attributable to asthma health status being composed of distinct components.
Effects of mandibular advancement on airway curvature and obstructive sleep apnoea severity
Authors: Tsuiki S. , Lowe A.A. , Almeida F.R. , Kawahata N. , Fleetham J.A.
Published: February 2004

In a curved tube, the amount of airflow appears to be influenced by the amount of curvature. The purpose of this study was to investigate changes in obstructive sleep apnoea (OSA) severity and awake velopharyngeal curvature in response to an anteriorly titrated mandibular position in 20 male OSA patients.

Baseline supine cephalometry was obtained before the initial insertion of a titratable oral appliance and follow-up supine cephalometry was undertaken after titration of the mandibular position with the appliance in place.

The mean apnoea/hypopnea index (AHI) before treatment (31.6±13.0 events·h−1) was significantly reduced (9.8±7.4 events·h−1) after titration of the mandibular position in all 20 patients. There was a significant increase in the anteroposterior calibre and the radius of the curvature of the anterior wall of the velopharynx in 14 good responders who exhibited an AHI reduction to ≤15. Similar observations were not found in six poor responders.

To conclude, an anteriorly titrated mandibular position reduced obstructive sleep apnoea severity, enlarged the velopharynx and diminished the curvature of the anterior velopharyngeal wall in good responders. It is proposed that this change in the upper airway curvature associated with mandibular advancement may effect obstructive sleep apnoea severity through its effect on airflow dynamics.
Outcome of incomplete systemic lupus erythematosus after 10 years
Authors: Hallengren C Ståhl , Nived O , Sturfelt G
Published: February 2004

The objective was to identify cases of incomplete systemic lupus erythematosus (SLE) within a defined population in southern Sweden, risk factors for development of complete SLE (≥4 classification criteria) and study outcome of the patients. During prospective retrieval of SLE cases within a defined population in southern Sweden, 28 patients (26 women, two men) with incomplete SLE (< 4 ACR criteria) were identified between 1981 and 1992. All patient records were reviewed and clinical and laboratory data were extracted from standardized formats. Organ damage was defined according to the SLICC/ACR damage index. During follow-ups, 16 of 28 patients developed complete SLE (median 13 years; range 10-20 years). The time to develop complete SLE varied between one and ten years with a median time of 5.3 years. Three patients were anti-DNA positive at inclusion; only one of them developed complete SLE. False positive Wasserman reaction and anti-cardiolipinantibodies (aCl) were only found in patients who developedcomplete SLE (P < 0.04; Fisher exact test). Six patientshad malar rash from the start and they all had complete SLE at follow-up (P < 0.04; Fisher exact test). Of eight patients with arthritis, three developed complete SLE. Thrombocytopeniawas only found in two patients, both developing complete disease. At follow-up, patients that developed complete SLE had high SLICC damage scores (mean 1.5) compared with patients that remained as incomplete SLE (mean 0.16). In conclusion, in this follow-up study of patients with incompleteSLE 57% developedcomplete disease after a median time of 5.3 years.Malar rash and aCl were predictors of complete SLE. Individuals that developed complete SLE were more prone to organ damage.
High-dose immunosuppression with autologous stem cell transplantation in severe refractory systemic lupus erythematosus
Authors: Lisukov I A , Sizikova S A , Kulagin A D , Kruchkova I V , Gilevich A V , Konenkova L P , Zonova E V , Chernykh E R , Leplina O Y , Sentyakova T N , Demin A A , Kozlov V A
Published: February 2004

Systemic lupus erythematosus(SLE) is an immune-mediateddisease that is responsiveto suppression or modulation of the immune system. Patients with SLE who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide (Cy), represent a subset of patients at high risk of early death. We investigated the efficacy and toxicity of high-dose immunosuppression and autologous hematopoietic stem cell transplantation (SCT) to treat such patients. Six patients (all female, age 15-29 years) with severe refractory SLE were enrolled in the clinic of our institution from 1998 to 2003. All patients were seriously ill, with SLE disease activity indices (SLEDAI) of 6-30, includingtwo cases with central nervoussystem lupus, one case with lung vasculitis, and three cases with nephritis and nephrotic syndrome. All patients were registered in the European Group for Blood and Marrow Transplantation (EBMT)/European League Against Rheumatism (EULAR) database. Previous immunosuppression included pulse Cy intravenous, prednisolone (standard doses and pulse therapy), oral Cy and azathioprine, with little or no effect on disease progression.Autologous hemopoietic stem cells were collected from bone marrow (n 4) or mobilized from peripheral blood with Cy and granulocyte colony-stimulating factor (G-CSF) (n 2). Pre-transplant conditioning regimens included BEAM + ATG (n 2), melphalan 140 mg/m2 etoposid 1600 mg/m2 (n 2) and Cy 200 mg/kg + ATG (n 2). Median time to an absolute neutrophil count (ANC) greater than 0.5 ×10 50 ×10 9/L and platelet count greater than 9/L was 13 and 15 days, respectively. Three patients died on days 11, 22 and 63 due to transplant-relatedcomplications. The follow-up is now 60 and six months for two patients (complete remission), and 42 months for one other patient (partial response). All patients had experienced multiple and severe episodes of infections pre-SCT and long-term history of corticosteroid therapy (3-14 years). We conclude that achievement of prolonged, corticosteroid-freeremissions is a reality. Judicious selection of patients earlier in disease or in remission, but with a high risk of relapse or further progression, will diminish transplantation-relatedmortality.
Mycophenolate mofetil combined with prednisone for diffuse proliferative lupus nephritis: a histopathological study
Authors: Ding Lei , Zhao Minghui , Zou Wanzhong , Liu Yuchun , Wang Haiyan
Published: February 2004

Mycophenolate mofetil (MMF) is a potential new treatment for diffuse proliferative lupus nephritis. This study examines the clinical and histopathological effects, and potential mechanisms, of combination MMF/prednisone therapy in diffuse proliferative lupus nephritis. Nine patients with diffuse proliferative lupus nephritis confirmed by renal biopsy received MMF/prednisone for six months when repeat biopsies were performed. Clinical and histopathological parameters of activity and chronicity were studied. Collagens were detected by Sirus red staining; leucocyte phenotype, osteopontin (OPN), fibrinectin (FN), a-smooth muscle actin (a-SMA) and TGF-b1 were detected by immunohistochemistry. The changes of clinical and histopathologic parameters were assessed and compared to histopathologic indicators. Eight of the nine patients achieved clinical remission; renal function deteriorated in one. Histopathological activity indices reduced significantly (9.56 + 2.83 versus 5.22 + 1.86, P < 0.01); however, the chronicity indices did not change (3.56 + 1.42 versus 3.22 + 1.20). T-cell and monocyte/macrophage infiltration, OPN expression and the percentage of proliferative cells in both glomerulus and tubulo-interstitiumdecreased significantly. Other features of chronic lesions, except for glomerular collagen deposition, did not change. In conclusion, MMF/prednisone therapy was effective for our patients with proliferative lupus nephritis. The active inflammatory lesions could be ameliorated through reduction of lymphocyte and monocyte/macrophage infiltration, inhibition of cell proliferation and downregulation of adhesive molecules. However, the chronic fibrotic lesions could not be significantly reduced.
Vascular and connective tissue diseases in the paediatric world
Authors: Falcini F
Published: February 2004

Despite the fact that in recent decades many advances have been made in classification, outcomes measurements and therapeutic regimens, connective tissue diseases remain a challenge for paediatric rheumatologists. Corticosteroids are still the first choice therapy in juvenile systemic lupus erythematosus (SLE); however, it is time for a new therapeutic approach with immunosuppressant drugs in order to obtain a more prolonged survivaland reduced organ system damage. A preventionof relapse of thromboembolic phenomena using low-dose aspirin is strongly suggested in children with anticardiolipin antibodies, particularly in those with SLE. The long-term prognosis in juvenile dermatomyositisis significantly improved due to a more aggressivetreatment with corticosteroidsand methotrexate. The treatment of Henoch-Schöenlein purpura is still under debate, and no agreement has been reached regarding the role of corticosteroids in the prevention of renal involvement. The management of the acute phase of Kawasaki disease is now well established, although there is controversy regarding the role of corticosteroids. It is still under debate how and whether to treat patients who do not fulfil the diagnostic criteria. Polyarteritis nodosa is a disease at risk of death and requires an aggressive approach with corticosteroids and immunosuppressants, while cutaneous polyarteritis needs a close control of an underlying streptococcus infection and prophylaxis with benzatin-penicillin to prevent relapses.
Is HLA class II susceptibility to primary antiphospholipid syndrome different from susceptibility to secondary antiphospholipid syndrome?
Authors: Freitas M VC , da Silva L M , Deghaide N HS , Donadi E A , Louzada-Júnior P
Published: February 2004

To assess whether the major histocompatibility complex (MHC) profile of patients presenting with primary antiphospholipid syndrome (PAPS) is different from that of patients with secondary antiphospholipid syndrome (SAPS), we studied 123 patients, 34 of whom presented PAPS and 35 SAPS due to systemic lupus erythematosus (SLE), 54 SLE patients without antiphospholipid syndrome (APS), and 166 controls. HLA-DRB1 and DQB1 alleles were typed using amplified DNA hybridized with sequence-specific primers. Compared to controls, PAPS patients exhibited a nonsignificantly increased frequency of DR53-associated alleles, and SAPS patients presented an increased frequency of HLA-DRB1* 03 alleles (corrected P 0.05). In addition, HLA-DRB1* 03 alleles were over-represented in SAPS patients presenting anticardiolipin antibody (aCL) (Pc 0.02), in SLE patients as a whole (Pc < 0.0001), and in SLE patients without APS (Pc 0.02). The frequency of aCL among SLE patients presenting or not HLA-DRB1* 03 alleles was closely similar. A trend to an increase in the frequency of the DQB1* 0604 allele (14.3 versus 4.2%, P 0.03) and of the DQB1*0302 allele (31.4 versus 12.7%, P 0.01) was observedin SAPS. Taken together, these results indicate that the association of SAPS with HLA-DRB1* 03 is due to the association with SLE and is not due to aCL, and suggest that the HLA class II profile of PAPS is different from that of SAPS.
Genetic algorithms applied to leather lay plan material utilization
Authors: Crispin A J , Clay P , Taylor G E , Bayes T , Reedman D
Published: February 2004

This paper presents a genetic algorithm method for the leather-nesting problem that involves cutting shoe upper components from hides so as to maximize material utilization. A significant proportion of the manufacturing cost of a pair of shoes is invested in the natural raw material, and so the efficient utilization of this resource is of prime importance. Consequently, the part nesting and cutting process is one of the most important stages in the manufacture of leather shoes. The genetic algorithm method presented for leather lay-planning is capable of handling some of the more intractable aspects of the problem, namely multiple non-convex shapes, irregularly shaped hides, directionality constraints and surface grading quality issues. The underlying encoding method is based on the use of the no-fit polygon (NFP), lay angles and directionality angle constraints. The NFP allows the genetic algorithm to evolve non-overlapping configurations. Lay-plan results are presented using standard shoe component shapes and scanned hide input data conforming to a grading scale commonly used in shoemaking.
Effects of the compression ratio on nitric oxide emissions for a spark ignition engine: Results from a thermodynamic cycle simulation
Authors: Caton J. A.
Published: February 2004

Past experimental work has not provided consistent results for the effects of the compression ratio on nitric oxide emissions. A thermodynamic cycle simulation for spark ignition engines, which included a formulation using multiple zones for the combustion process, was used to determine the effects of the compression ratio on nitric oxide emissions. An important feature of this simulation is the use of an adiabatic zone to capture the high temperatures in the core region of the cylinder better during combustion. This study was completed for a commercial, 5.71 spark ignition V-8 engine operating at a part load condition at 1400r/min with an equivalence ratio of 1.0 and ‘MBT’ (maximum brake torque) spark timing. The effects of the compression ratio on nitric oxide emissions are shown to be the result of a complex set of interactions involving the combustion gas temperature, pressure, species concentrations, chemical kinetics and other thermodynamic quantities. For the base case condition, the nitric oxide concentration first increases and then decreases with increasing compression ratio. This is shown to be a result of the relative values of the nitric oxide moles formed, the combustion gas volume and the moles of the exhaust gas. The computed results are shown to agree qualitatively with experimental values from the literature.
Dental Education in the 21st Century
Authors: Seward Margaret
Published: February 2004

The continuum of dental education has been greatly strengthened by the General Dental Council's educational initiatives during the past five years and these are described in this paper: lifelong learning and recertification will reassure the public and full integration of team members through statutory registration with one self-regulatory body is an innovation in the regulation of health professionals. Future training and educational strategies, including the health science concept, for team members are explored.
The Structure of the Dental Workforce in the 21st Century
Authors: Scarrott Diana M
Published: February 2004

Graham Try (page 9) has suggested that the UK is heading towards dentist shortage. This paper picks up the story from there, speculating on how a shortage of dentists might stimulate changes in working methods. The market place will look for workforce configurations which make business sense at practice level and which deliver services in a form which patients find helpful and convenient. Although some dental procedures can be carried out by people with less training than dentists, this may not contribute to economic efficiency and could make the customer service experience less appealing. Changes in the structure of the workforce may therefore be less radical than has sometimes been suggested. Much depends on how decision-making and regulatory processes evolve. It seems likely that local and practice level decision-making will grow at the expense of central planning.