bluuebunny/crossref_metadata_2025 huggingface dataset:
Placebo Response in Cluster Headache Trials: A Review
Authors: Nilsson Remahl AIM , Laudon Meyer E , Cordonnier C , Goadsby PJ
Published: September 2003

Probably because of its relative rarity as primary headache, there are few well-controlled clinical trials on cluster headache (CH) patients. Due to the severity of the pain, the placebo response in CH has been considered to be small. During the eighties the first double-blind, placebo-controlled trials were reported, and placebo responses demonstrated. Here we review the placebo response in CH trials in order to assess its magnitude and consider how future studies can be optimized. Six trials were identified with a double-blind, placebo-controlled, cross-over design testing treatments of acute CH. For those with a primary endpoint set to no or mild headache the placebo responses varied from 7 to 42%. In five of seven prophylactic trials, using a double-blind, placebo-controlled, parallel-group design, the placebo was merely used to set a baseline for comparison. The placebo responses were reported in only two trials. Here the response varies from 14 to 43%, the lowest value was reported using the strict endpoint; cessation of headache attacks. We conclude that a placebo response exists in trials of drugs on CH patients. Furthermore, this placebo response is of the same magnitude as that seen in migraine studies. We recommend the use of IHS guidelines when designing new trials. The possibility of a genuine biological mechanism responsible for the placebo response is discussed.
The Effect of Trigeminal Nociceptive Stimulation on Blink Reflexes and Pain Evoked by Stimulation of the Supraorbital Nerve
Authors: Drummond PD
Published: September 2003

The aim of this study was to investigate the effect of painful conditioning stimuli on pain and blink reflexes to supraorbital nerve stimulation. Electromyograph activity was recorded bilaterally from the orbicularis oculi muscles in 13 normal participants in response to low (2.3 mA) and high-intensity (18.6 mA) electrical stimulation of the left supraorbital nerve before, during and after the application of ice to the left or right temple or immersion of the left hand in ice-water for 60 s. The pain evoked by the high-intensity electrical stimulus was greater during painful conditioning stimulation of the ipsilateral temple than during the recovery period afterwards, and was greater than during painful conditioning stimulation of the contralateral temple. These findings imply that spatial summation of nociceptive signals across different divisions of the trigeminal nerve can heighten pain. However, painful conditioning stimulation, particularly to the right temple, strongly suppressed the R2 component of the blink reflex to the low-intensity stimulus, and also suppressed R2 to the high-intensity stimulus. Thus, an inhibitory influence (e.g. diffuse noxious inhibitory controls) appeared to mask ipsilateral segmental facilitation of R2 during ice-induced headache. This finding contrasts with recent electrophysiological evidence of trigeminal sensitization in migraine.
The Prevalence and Disability Burden of Adult Migraine in England and their Relationships to Age, Gender and Ethnicity
Authors: Steiner TJ , Scher AI , Stewart WF , Kolodner K , Liberman J , Lipton RB
Published: September 2003

This study estimates the 1-year prevalence of migraine in adults in England in relation to the major demographic variables of age, gender and ethnicity, and describes some of its features, including aspects of consequential disability. A telephone survey was conducted of a random sample ( n = 4007) of the population aged 16-65 years of mainland England using a previously validated diagnostic interview. The response rate was 76.5%. Overall, 7.6% of males and 18.3% of females reported migraine with or without aura within the last year meeting diagnostic criteria closely approximate to those of the International Headache Society. Prevalence of migraine varied with age, rising through early adult life and declining in the late 40s and early 50s. Prevalence was higher in Caucasians than in other races. Attack rates were ≥ 1/month in most migraineurs, and most experienced interference with daily activities in ≥ 50% of their attacks. On average, an estimated 5.7 working days were lost per year for every working or student migraineur, although the most disabled 10% accounted for 85% of the total. Results were in keeping with those from surveys in other countries. If these findings in mainland England are projected to the entire UK population, we estimate that 5.85 million people aged 16-65 years experience 190 000 migraine attacks every day and lose 25 million days from work or school each year because of them. Migraine is an important public health problem in the UK, associated with very substantial costs.
Cognitive Processing in Headache Associated with Sexual Activity
Authors: Frese A , Frese K , Ringelstein EB , Husstedt I-W , Evers S
Published: September 2003

Cognitive processing as measured by event-related potentials (ERP) in patients suffering from the explosive subtype of headache associated with sexual activity (HSA type 2) was investigated. Visual ERP were measured in 24 patients with HSA type 2 outside the headache period. The differences of the first and the second part of measurement were evaluated separately to determine the amount of cognitive habituation. Twenty-four sex- and age-matched healthy subjects and 24 patients with migraine without aura served as controls. A missing increase of P3 latency during the second part of the measurement was found in 79% of patients with HSA type 2 and in 75% with migraine, but only in 17% of the healthy controls ( P < 0.001). The P3 amplitude was increased during the second part in 71% of patients with HSA type 2 and in 79% with migraine, but only in 33% of the healthy controls ( P = 0.02). Mean P3 latency was decreased and mean P3 amplitude was increased during the second part of the measurement in HSA type 2 and in migraine but not in the healthy control group. Patients with HSA type 2 have a loss of cognitive habituation as measured by ERP. This specific information processing is very similar to that in migraine observed in previous studies.
Subclinical Sensory Abnormalities in Trigeminal Neuralgia
Authors: Sinay VJ , Bonamico LH , Dubrovsky A
Published: September 2003

Trigeminal neuralgia is considered as a paroxysmal single nerve phenomenon. Abnormal sensory perception has been previously described in 15-25% of patients with clinical examination. Quantitative sensory testing (QST) was used to evaluate sensory perception in patients with idiopathic trigeminal neuralgia (ITN). Nine patients and 10 normal control subjects were evaluated in all six trigeminal branches. QST abnormalities were found in the symptomatic division and in the other two branches on the same side. Minor contralateral changes were also found. Differences consisted of cold and warm hypoaesthesia and higher cold and heat pain thresholds in patients. All differences proved statistically significant. Our findings suggest that trigeminal neuralgia is not only a paroxysmal single nerve disorder, but also that other higher structures may be involved.
Cluster Headache Prevalence. Vågå Study of Headache Epidemiology
Authors: Sjaastad O , Bakketeig LS
Published: September 2003

In the Vågå study of headache epidemiology, a search was made also for cluster headache. Of the available 18-65-year-old dalesmen, 1838 (88.6%) could be examined personally (O.S.) – 51.3% females and 48.7% males. Based on current International Headache Society criteria, cluster headache seemed to be present in seven dalesmen, one female and six males (corresponding to a total prevalence of 381 per 100 000; 95% confidence interval (CI) 153-783 per 100 000). Except for the female gender, the female case was fairly typical. In one case, there were short-lasting bouts (‘minibouts’). It was felt that this also was a genuine case of cluster headache. If one excluded the latter case, there would be one female and five males [a prevalence of 106 per 100 000 for females, and 558 per 100 000 for males, giving a prevalence in the total population of 326 per 100 000 (95% CI 120-709 per 100 000)]. The confidence interval was considerable. This study therefore does not give a clear indication as to prevalence.
Postural Headache In A Patient With Marfan's Syndrome
Authors: Ferrante E , Citterio A , Savino A , Santalucia P
Published: September 2003

A 26-year-old man with Marfan's syndrome had postural headache. Brain MRI with gadolinium showed diffuse pachymeningeal enhancement. MRI myelography revealed bilateral multiple large meningeal diverticula at sacral nerve roots level. He was suspected to have spontaneous intracranial hypotension syndrome. Eight days later headache improved with bed rest and hydration. One month after the onset he was asymptomatic and 3 months later brain MRI showed no evidence of diffuse pachymeningeal enhancement. The 1-year follow-up revealed no neurological abnormalities. The intracranial hypotension syndrome likely resulted from a CSF leak from one of the meningeal diverticula. In conclusion patients with spinal meningeal diverticula (frequently seen in Marfan's syndrome) might be at increased risk of developing CSF leaks, possibly secondary to Valsalva maneuver or minor unrecognizedtrauma.
‘Mum's the Word!': Maternal Accounts of Dealings with the Professional World
Authors: Todd Stuart , Jones Stephanie
Published: September 2003

Background  This paper describes a study of one aspect of the lives of mothers of children with intellectual disabilities. It focuses on their perspectives of their dealings with the professional and service worlds. Much attention has been given in recent years to developing and co‐ordinating a multiprofessional and multiagency network of support around families. Although such aims can be seen as beneficial for families, there is also good reason to expect these to present problematic experiences for family carers.

Methods  Data are presented and analysed in this paper on mothers' perceptions of their dealings with professionals. The sample consisted of 30 mothers of young people with intellectual disabilities. The data were obtained by qualitative interviews.

Results and discussion  Overall, the study confirmed that mothers' dealings with professionals were highly problematic for them. They felt that such encounters could be based upon conflict and that their worth and character as mothers were being continually scrutinized. However, the data show that mothers were willing to challenge professional perspectives of their children and their needs. They embraced advocacy for their sons and daughters as part‐and‐parcel of being a mother. However, in doing so, they were much more hesitant and reluctant to raise any needs and aspirations for their own lives. They fear that in giving these voice, they could be seen and typified as selfish mothers. That is, their struggles to be taken as advocates for their sons and daughters would be undermined. The implications of these findings for research and service development are discussed.
Paying the Piper and Calling the Tune? The Relationship Between Parents and Direct Payments for People with Intellectual Disabilities
Authors: Williams Val , Simons Ken , Gramlich Stacey , McBride Gordon , Snelham Natasha , Myers Brian
Published: September 2003

Background  The aim of this paper is to investigate the role parents are playing in direct payments provision for their son or daughter with intellectual disabilities.

Materials and methods  The paper draws on a UK‐wide inclusive research project, carried out by researchers who were members of an organization of people with intellectual disabilities. The purpose of the project as a whole was to explore what support works best for people with intellectual disabilities to access direct payments provision in the UK, and one of the key supports for certain people was found to be parents and families.

Results  Drawing on interviews with 29 family carers, the researchers found that parents were often strong advocates of independence for their son or daughter, and only acted as barriers to direct payments when they did not have sufficient information. Parents were found to be playing significant roles as initiators, managers and supporters of direct payments for their son or daughter; however, these roles were matched by important gains in quality of life and relationships within the family.

Conclusions  The paper considers the implications of the power balance between persons with intellectual disabilities, their parents and their staff. Direct payments can alter that balance radically, but it is still important to have a good, independent direct payments support scheme to enable the person with intellectual disabilities to be in control.
Just Getting on with it: Exploring the Service Needs of Mothers Who Care for Young Children with Severe/Profound and Life‐Threatening Intellectual Disability
Authors: Redmond Bairbre , Richardson Victoria
Published: September 2003

Background  This study interviewed mothers (n= 17) of children aged 4 years and under with severe/profound intellectual disability, some with attendant complex medical, life‐limiting conditions.

Methods  The study explored the mothers' views of the usefulness of the financial, practical and emotional supports being offered to them and their suggestions for service improvements.

Results  The study reveals these mothers to be engaged in stressful but skilled care of their children with a clear wish to continue caring for their child in the family home. Mothers frequently referred to the process of gaining useful information on services as ‘haphazard’ and most of the services offered to them as uncoordinated, unreliable and difficult to access. The study reveals that many of these children's needs are not being adequately met by either the intellectual disability services or the acute medical services, and some families are forced to privately finance services such as physiotherapy and speech therapy.

Conclusions  The data reveal that mothers want services offered to them in their own home, particularly short home‐based respite, which would offer them short breaks to rest or engage in part‐time employment. The study concludes that a reliable and flexible service response, including a comprehensive information and advocacy support is indicated for these families.
Parents of Children with Intellectual Disabilities: Their Expectations and Experience of Genetic Counselling
Authors: Barr Owen , Millar Rob
Published: September 2003

Background  Following the birth of a child, parents and other family members have to adapt to their new circumstances. This process takes time and can become more complex when the child is suspected or diagnosed as having intellectual disabilities. When a child has a disability, parents often seek answers as to the origin and nature of the condition as part of the adaptation process. For some parents, this will result in genetic investigations and could lead to the provision of personal genetics about the child and parents.

Materials and methods  This paper reports a mixed‐method project that combined questionnaires prior to and interviews after an appointment with a geneticist. The project sought to identify the expectations and experience of parents who had a child referred to specialist genetics services.

Results and conclusions  The findings identify that parents felt largely unprepared for their appointment and reported feelings of failing to maximize the opportunity present. The need for more effective liaison between specialist regional and local primary care and learning disability services is also highlighted. Parents made practical suggestions relevant to all the above services about how they could be better supported at this difficult stage in the adaptation process.
The Disclosure Process and its Impact on South Asian Families with a Child with Severe Intellectual Disabilities
Authors: Hatton Chris , Akram Yasmeen , Robertson Janet , Shah Robina , Emerson Eric
Published: September 2003

Background  Although several research studies have investigated parental experiences of the disclosure process in White families with a child with severe disabilities, little work has focused on the experiences of South Asian families.

Materials and methods  This study aimed to provide a rich picture of the disclosure experiences of South Asian parents of a child with severe intellectual disabilities, using semi‐structured qualitative interviews with 26 parents over two time points, and structured quantitative interviews with 136 parents.

Results  Parents reported variable experiences of the disclosure process, with many parents experiencing disclosure in the wrong language for them and most parents reporting little post‐disclosure support. Parents identified good practice in disclosure as prompt disclosure in the appropriate language, with the partner present (where possible), with emotional support as part of the process, with clear and practical information, and linked to post‐disclosure support from a keyworker.

Conclusions  Good practice in disclosure was also associated with parental understanding of their child, and parents being more likely to mobilize informal and formal supports. The implications of these findings are discussed.
Ultrastructural correlates of synapse withdrawal at axotomized neuromuscular junctions in mutant and transgenic mice expressing the Wld gene
Authors: Gillingwater Thomas H. , Ingham Cali A. , Coleman Michael P. , Ribchester Richard R.
Published: September 2003

We carried out an ultrastructural analysis of axotomized synaptic terminals in Wlds and Ube4b/Nmnat (Wld) transgenic mice, in which severed distal axons are protected from Wallerian degeneration. Previous studies have suggested that axotomy in juvenile (< 2 months) Wld mice induced a progressive nerve terminal withdrawal from motor endplates. In this study we confirm that axotomy‐induced terminal withdrawal occurs in the absence of all major ultrastructural characteristics of Wallerian degeneration. Pre‐ and post‐synaptic membranes showed no signs of disruption or fragmentation, synaptic vesicle densities remained at pre‐axotomy levels, the numbers of synaptic vesicles clustered towards presynaptic active zones did not diminish, and mitochondria retained their membranes and cristae. However, motor nerve terminal ultrastructure was measurably different following axotomy in Wld transgenic 4836 line mice, which strongly express Wld protein: axotomized presynaptic terminals were retained, but many were significantly depleted of synaptic vesicles. These findings suggest that the Wld gene interacts with the mechanisms regulating transmitter release and vesicle recycling.
Estimation of nuclear volume as an indicator of maturation of glial precursor cells in the developing rat spinal cord: a stereological approach
Authors: McMahon S. S. , Dockery P. , McDermott K. W.
Published: September 2003

Studies on nuclear volume have shown that it is an indication of the state of differentiation of cells. This study provides evidence indicating increasing nuclear volume during cell maturation. Using unbiased stereological techniques, nuclear volume of both proliferating and non‐proliferating glial cells was analysed in the developing spinal cord. Proliferating glial precursor cells were identified using a 5‐bromo‐21‐deoxyuridine (BrdU) incorporation assay. The nuclear volume of BrdU‐labelled cells and unlabelled cells was determined in both periventricular regions and the white matter of the cord at different embryonic ages. In the periventricular region BrdU‐labelled nuclei were smaller than unlabelled nuclei at all ages examined. These labelled cells represent dividing undifferentiated progenitors. The unlabelled neighbouring cells with larger nuclei represent a more differentiated population. In the white matter BrdU‐labelled nuclei were of similar volume to the unlabelled nuclei. Both of these groups represent glial precursor cells that have migrated from deeper regions and are at similar stages of differentiation, perhaps with different proliferative potential. These findings indicate that the nuclear volume of early glial cells increases as these cells migrate and differentiate.
Zebrin II compartmentation of the cerebellum in a basal insectivore, the Madagascan hedgehog tenrec Echinops telfairi
Authors: Sillitoe Roy V. , Künzle Heinz , Hawkes Richard
Published: September 2003

The mammalian cerebellum is histologically uniform. However, underlying the simple laminar architecture is a complex arrangement of parasagittal stripes and transverse zones that can be revealed by the expression of zebrin II/aldolase C. The cerebellar cortex of rodents, for example, is organized into four transverse zones: anterior, central, posterior and nodular. Within the anterior and posterior zones, parasagittal stripes of Purkinje cells expressing zebrin II alternate with those that do not. Zonal boundaries appear to be independent of cerebellar lobulation. To explore this model further, and to broaden our understanding of the evolution of cerebellar patterning, zebrin II expression has been studied in the cerebellum of the Madagascan hedgehog tenrec (Echinops telfairi), a basal insectivore with a lissiform cerebellum with only five lobules. Zebrin II expression in the tenrec reveals an array of four transverse zones as in rodents, two with homogeneous zebrin II expression, two further subdivided into stripes, that closely resembles the expression pattern described in other mammals. We conclude that a zone‐and‐stripe organization may be a common feature of the mammalian cerebellar vermis and hemispheres, and that zonal boundaries and cerebellar lobules and fissures form independently.
Age‐associated plasticity in the intrinsic innervation of the ovine rumen
Authors: Pfannkuche Helga , Schellhorn Corinna , Schemann Michael , Aschenbach Jörg R. , Gäbel Gotthold
Published: September 2003

The rumen of adult sheep functions as a large fermentation chamber. In the newborn suckling ruminant, the rumen is bypassed and milk enters the abomasum directly. It was the aim of our study to investigate whether the transmitter content of intrinsic nerves changes with the developmental stage. The neurochemical code of myenteric neurons in the rumen from suckling lambs, fattened lambs and adult sheep was determined by using quadruple immunohistochemistry against choline‐acetyltransferase (ChAT), nitric oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP). Three neurochemically distinct subpopulations were identified within the rumen. They expressed the code ChAT/–, ChAT/SP and NOS/VIP. The number of ChAT/SP neurons did not change during development. It was 62% in the newborn lamb and remained stable in fattened lambs (63%) and adult sheep (63%). By contrast, the number of ChAT/– neurons decreased significantly from 20% in suckling lambs to 11% and 7% in fattened lambs and adult sheep, respectively. Simultaneously, the proportion of NOS/VIP neurons increased from 16% in suckling lambs to 29% in adult sheep. The increase in the proportion of NOS/VIP immunoreactive neurons indicates an adaptation to large volumes of ingesta at the beginning of roughage intake and rumination. We conclude that the age‐associated changes in neurochemical code of myenteric neurons in the forestomach are related to the adaption of the rumen to different functional properties during development.
Segmentation in staged human embryos: the occipitocervical region revisited
Authors: Müller Fabiola , O'Rahilly Ronan
Published: September 2003

The first seven somites, the rhombomeres, and the pharyngeal arches were reassessed in 145 serially sectioned human embryos of stages 9–23, 22 of which were controlled by precise graphic reconstructions. Segmentation begins in the neuromeres, somites and aortic arches at stage 9. The following new observations are presented. (1) The first somite in the human, unlike that of the chick, is neither reduced in size nor different in structure, and it possesses sclerotome, somitocoel and dermatomyotome. (2) Somites 1–4, unlike those of the chick, are related to rhombomere 8 (rather than 7 and 8) and are caudal to pharyngeal arch 4 (rather than in line with 3 and 4). (3) Occipital segment 4 resembles a developing vertebra more than do segments 1–3. (4) The development of the basioccipital resembles that of the first two cervical vertebrae in that medial and lateral components arise in a manner that differs from that in the rest of the vertebral column. (5) The two groups of somites, occipital 1–4 and cervical 5–7, each form a median skeletal mass. (6) An ‘S‐shaped head/trunk interface’, described for the chick and unjustifiably for the mouse, was not found because it is not compatible with the topographical development of the otic primordium and somite 1, between which neural crest migrates without hindrance in mammals. (7) Occipital segmentation and related features are documented by photomicrographs and graphic interpretations for the first time in the human. It is confirmed that the first somite, unlike that of the chick, is separated from the otic primordium by a distance, although the otic anlage undergoes a relative shift caudally. The important, although frequently neglected, distinction between lateral and medial components is emphasized. Laterally, sclerotomes 3 and 4 delineate the hypoglossal foramen, 4 gives rise to the exoccipital and participates in the occipital condyle, 5 forms the posterior arch of the atlas and 6 provides the neural arch of the axis, which is greater in height than the arches of the other cervical vertebrae. Medially, the perinotochord and migrated sclerotomic cells give rise to the basioccipital as well as to the vertebral centra, including the tripartite column of the axis. Registration between (1) the somites and (2) the occipital and cervical medial segments becomes interrupted by the special development of the axis, the three components of which come to occupy the height of only 2½ segments.
In vivo time‐course of the angiogenic response induced by multiple myeloma plasma cells in the chick embryo chorioallantoic membrane
Authors: Ribatti Domenico , De Falco Giuseppe , Nico Beatrice , Ria Roberto , Crivellato Enrico , Vacca Angelo
Published: September 2003

In this study, we set out to make a fine characterization of the angiogenic response induced by plasma cells obtained from patients with active‐multiple myeloma (MM), in comparison with cells obtained from patients with non‐active MM and benign lesions such as monoclonal gammopathy of undetermined significance (MGUS), in the chick embryo chorioallantoic membrane (CAM) assay. To achieve this we investigated the time‐course of the angiogenic response induced by gelatin sponges soaked in the cell suspensions and implanted on the CAM surface from day 8 to day 12 of incubation by evaluating the number of vessels, of the vessel bifurcation and the intervascular distance at 24, 48, 72 and 96 h after the implants. The results show that plasma cell suspensions obtained from patients with active MM induce a vasoproliferative response that was significantly higher than that induced by cell suspensions obtained from patients with non‐active MM or with MGUS, which is also a function of the day of implantation. In fact, implants made from day 8 to day 10 induce a strong angiogenic response, whereas those made from day 11 to day 12 do not. This finding might depend on the fact that CAM endothelium exhibits an intrinsically high mitotic rate until day 10. Thereafter, the endothelial mitotic index declines rapidly, and consequently cell suspensions implanted on the CAM of successively older embryos are not able to induce a vasoproliferative response in parallel with the reduced rates of growth of the CAM's endothelial cells.
Pectoral fin development in the Baikalian viviparous golomyankas (Comephoridae; Cottoidei), with a remark on eggs and embryos of Comephorus baicalensis (Pallas)
Authors: Jakubowski Michał , Tugarina Polina Y. , Żuwała Krystyna
Published: September 2003

Measurements of pectoral fin (PF) growth in relation to standard body length (SL) for Comephorus dybowskii (SL: 14–126 mm) and C. baicalensis (SL: 22–173 mm) were made and compared with corresponding data obtained for 13 other Baikalian cottoid species (sculpins). The allometry for the PF/SL relationships (Y = a + bX) is clearly biphasic. Expressed in percentages, these values for the larval period of C. dybowskii[Yp = −28.886 + (2.419X)] are much higher than for C. baicalensis[Yp = −11.904 + (1.233X)]. The postnatal period of development of the golomyanka up to 30–35 mm SL is considered to be the larval stage. In the postlarval period, growth of pectoral fin and the body in C. dybowskii are directly proportional [Yp′ = 48.92 + (−0.009X)] whereas in C. baicalensis they rise slightly [Yp′ = 30.966 + (0.0505X)]. Absence of the air bladder characterizes all Baikalian cottoid species, including the golomyankas. Various species of the golomyanka differ in the ways of obtaining neutral buoyancy. It is supposed that large pectoral fins guarantee behavioural buoyancy in small species such as C. dybowskii, whereas in C. baicalensis, obtaining much larger body size but lower PFp/SL index, the buoyancy is gained mainly due to the accumulation of large amount of lipids. This paper also documents the ovary and advanced embryos of C. baicalensis.
Changes in GAD67 mRNA expression evidenced by in situ hybridization in the brain of R6/2 transgenic mice
Authors: Gourfinkel‐An I. , Parain K. , Hartmann A. , Mangiarini L. , Brice A. , Bates G. , Hirsch E. C.
Published: August 2003

Huntington's disease is an autosomal dominant disorder with degeneration of medium size striatal neurones. As the disease evolves, other neuronal populations are also progressively affected. A transgenic mouse model of the disease (R6/2) that expresses exon 1 of the human Huntington gene with approximately 150 CAG repeats has been developed, but GABA concentrations are reported to be normal in the striatum of these animals. In the present study, we analysed the status of GABAergic systems by means of glutamic acid decarboxylase (GAD)67 mRNA in situ hybridization in the brain of R6/2 transgenic mice and wild‐type littermates. We show that GAD67 expression is normal in the striatum, cerebellum and septum but decreased in the frontal cortex, parietal cortex, globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata of R6/2 mice. These data, which may, in part, account for the behavioural changes seen in these animals, indicate that at 12.5 weeks of age the pathological features seen in the mice differ from those seen in humans with Huntington's disease.
Characterisation of the actions of group I metabotropic glutamate receptor subtype selective ligands on excitatory amino acid release and sodium‐dependent re‐uptake in rat cerebrocortical minislices
Authors: Fazal Abidali , Parker Fred , Palmer Alan M. , Croucher Martin J.
Published: August 2003

In this study we have tested the effects of a wide range of metabotropic glutamate receptor ligands on (i) depolarisation‐evoked efflux of pre‐accumulated d‐[3H]aspartic acid (d‐[3H]asp) from rapidly superfused rat cerebrocortical minislices, and (ii) Na+‐dependent uptake of d‐[3H]asp into cerebrocortical tissue. Transient elevations in extracellular K+ produced concentration‐dependent increases in d‐[3H]asp efflux. A submaximally effective concentration (50 mm) was used in all subsequent experiments. The broad‐spectrum mGlu receptor agonist (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid [(1S,3R)‐ACPD; EC50 17.8 μm], the group I mGlu‐selective agonist (S)‐3,5‐dihydroxyphenylglycine [(S)‐3,5‐DHPG; EC50 0.5 μm] and the mGlu5 receptor subtype‐selective agonist (RS)‐2‐chloro‐5‐hydroxyphenylglycine [(RS)‐CHPG; EC50 7.3 μm] all concentration‐dependently potentiated high K+‐evoked d‐[3H]asp efflux in the absence of effects on basal outflow of radiolabel. At concentrations selective for mGlu1 receptors, the antagonists (RS)‐1‐aminoindan‐1,5‐dicarboxylic acid [(RS)‐AIDA; 10–300 μm]; (+)‐2‐methyl‐4‐carboxyphenylglycine [LY367385; 1–100 μm] and 7‐hydroxyiminocyclopropan[b]chromen‐1a‐carboxylate ethyl ester [CPCCOEt, 1–30 μm] all failed to inhibit responses to (S)‐3,5‐DHPG. However, the broad‐spectrum mGlu receptor antagonist (S)‐α‐methyl‐4‐carboxyphenylglycine [(S)‐MCPG; IC50 88.5 μm] together with the recently described mGlu5‐selective antagonists, 2‐methyl‐6‐(phenylethynyl)‐pyridine (MPEP; IC50 0.6 μm), 6‐methyl‐2‐(phenyl‐azo)‐3‐pyridinol (SIB‐1757; IC50 4.4 μm) and (E)‐2‐methyl‐6‐(2‐phenylethenyl)pyridine (SIB‐1893; IC50 3.1 μm), at mGlu5‐selective concentrations, all powerfully and concentration‐dependently inhibited (S)‐3,5‐DHPG‐evoked responses. Two selective excitatory amino acid (EAA) uptake inhibitors, l‐trans‐2,4‐pyrrolidine dicarboxylate (l‐trans‐2,4‐PDC; IC50 229 μm) and dl‐threo‐β‐benzyloxyaspartate (dl‐TBOA; IC50 665 μm) both inhibited the Na+‐dependent uptake of d‐[3H]asp into cerebrocortical minislices. Importantly, none of the mGlu ligands utilized in the present study significantly inhibited d‐[3H]asp uptake at concentrations shown to potentiate K+‐evoked efflux. These data demonstrate for the first time that mGlu5 ligands modulate extracellular EAA concentrations by a direct effect on mGlu5‐type autoreceptors on EAA nerve terminals as they evoke clear changes in EAA release in the absence of any effects on EAA uptake. Selective mGlu5 receptor antagonists that show high potency and good central bioavailability may provide novel classes of neuroprotective agents for the treatment of brain disorders associated with abnormal EAAergic neurotransmission.
Role of nitric oxide in rotenone‐induced nigro‐striatal injury
Authors: He Yi , Imam Syed Z. , Dong Zaojun , Jankovic Joseph , Ali Syed F. , Appel Stanley H. , Le Weidong
Published: August 2003

Rotenone, a widely used pesticide, causes a syndrome in rats that mimics, both behaviorally and pathologically, the symptoms of Parkinson's disease. The present study evaluated the role of nitric oxide in rotenone‐induced nigro‐striatal injury. After administration of rotenone in rats for 40 days, there was a moderate but significant injury of the nigro‐striatal pathway indicated by a 47% decrease in striatal dopamine levels and a 28% loss of substantia nigra tyrosine hydroxylase‐immunopositive neurons. Furthermore, a significant (37%) increase in the number of cells positive for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH‐d) in the striatum was observed, accompanied by a 83% increase in nitric oxide synthase (NOS) activity and a significant increase in the production of 3‐nitrotyrosine (3‐NT). There was a significant increase (45%) in the optical density of NADPH‐d staining and an increase (72%) in NOS activity in the substantia nigra. Moreover, administration of the neuronal NOS inhibitor 7‐nitroindazole significantly attenuated the increased NOS activity and 3‐NT production, and provided significant protection against rotenone‐induced nigro‐striatal injury. Our data suggest that chronic rotenone administration can lead to significant injury to the nigro‐striatal system, mediated by increased generation of nitric oxide.
A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114
Authors: Crystal Adam S. , Giasson Benoit I. , Crowe Alexander , Kung Mei‐Ping , Zhuang Zhi‐Ping , Trojanowski John Q. , Lee Virginia M.‐Y.
Published: August 2003

Proteinaceous inclusions with amyloidogenic properties are a common link between many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Histological and in vitro studies of amyloid fibrils have advanced the understanding of protein aggregation, and provided important insights into pathogenic mechanisms of these neurodegenerative brain amyloidoses. The classical amyloid dyes Congo Red (CR) and thioflavin T and S, have been used extensively to detect amyloid inclusions in situ. These dyes have also been utilized to monitor the maturation of amyloid fibrils assembled from monomer subunits in vitro. Recently, the compound (trans,trans)‐1‐bromo‐2,5‐bis‐(3‐ hydroxycarbonyl‐4‐hydroxy)styrylbenzene (BSB), derived from the structure of CR, was shown to bind to a wide range of amyloid inclusions in situ. More importantly it was also used to label brain amyloids in live animals. Herein, we show that an analogue of BSB, (trans,trans)‐1‐bromo‐2,5‐bis‐(4‐hydroxy)styrylbenzene (K114), recognizes amyloid lesions, and has distinctive properties which allowed the quantitative monitoring of the formation of amyloid fibrils assembled from the amyloid‐β peptide, α‐synuclein, and tau.
Effect of subthalamic nucleus or entopeduncular nucleus lesion on levodopa‐induced neurochemical changes within the basal ganglia and on levodopa‐induced motor alterations in 6‐hydroxydopamine‐lesioned rats
Authors: Périer Céline , Marin Concepció , Jimenez Anna , Bonastre Mercè , Tolosa Eduardo , Hirsch Etienne C.
Published: August 2003

Inactivation of the subthalamic nucleus (STN) or the internal segment of the pallidum (GPi)/entopeduncular nucleus (EP) by deep brain stimulation or lesioning alleviates clinical manifestations of Parkinson's disease (PD) as well as reducing the side‐effects of levodopa treatment. However, the effects of STN or entopeduncular nucleus (EP) lesion on levodopa‐related motor fluctuations and on neurochemical changes induced by levodopa remain largely unknown. The effects of such lesions on levodopa‐induced motor alterations were studied in 6‐hydroxydopamine (6‐OHDA)‐lesioned rats and were assessed neurochemically by analyzing the functional activity of the basal ganglia nuclei, using the expression levels of the mRNAs coding for glutamic acid decarboxylase and cytochrome oxidase as molecular markers of neuronal activity. At the striatal level, preproenkephalin (PPE) mRNA levels were analyzed. We found in 6‐OHDA‐lesioned rats that a unilateral STN or EP lesion ipsilateral to the 6‐OHDA lesion had no effect on either the shortening in the duration of the levodopa‐induced rotational response or the levodopa‐induced biochemical changes in the basal ganglia nuclei. In contrast, overexpression of PPE mRNA due to levodopa treatment was reversed by the STN or EP lesion. Our study thus shows that lesion of the EP or STN may counteract some of the neurochemical changes induced by levodopa treatment within the striatum.
Distribution of alien plant species in relation to human disturbance on the Georgia Sea Islands
Authors: Rodgers J. C. , Parker K. C.
Published: August 2003

Abstract. This study investigates the effects of human disturbance and environmental factors on the distribution of alien plant species on the Georgia Sea Islands (GSI), USA. We sampled the absolute cover of native and alien plant species on two tourist islands (St. Simons Island and Jekyll Island) and on two protected National Wildlife Refuge Islands (Blackbeard Island and Wassaw Island). On each island, vegetation composition and environmental variables (soil properties and salt spray) were measured in two habitats that differed substantially in their degree of environmental stress, the more exposed primary dune and the more sheltered and inland maritime forest. Sites were further stratified within each habitat into areas that had different levels of human disturbance. Many alien species were present on all islands and the absolute cover of alien species was not significantly different among islands even though they varied substantially in their degree of accessibility and overall land use. Alien plant cover was appreciably greater in severely disturbed sites than in less disturbed sites on all islands and within both habitats. However, the difference between disturbance categories was much less pronounced in the primary dunes where human disturbance agents do not mitigate the harsh environmental conditions of this habitat (salt spray and saline soils). Alien plant abundance on the GSI is evidently more dependent upon the availability of disturbed ground than the degree of accessibility or overall island development. It appears that human disturbance increases alien cover in general, but in environments where the stress levels are not mitigated, human disturbance does little to foster alien invasions.
A prolonged postinspiratory pause enhances CO2 elimination by reducing airway dead space
Authors: Uttman Leif , Jonson Björn
Published: September 2003

Background: CO2 elimination per breath (VCO2,T) depends primarily on tidal volume (VT). The time course of flow during inspiration influences distribution and diffusive mixing of VT and is therefore a secondary factor determining gas exchange. To study the effect of a postinspiratory pause we defined ‘mean distribution time’ (MDT) as the mean time given to inspired gas for distribution and diffusive mixing within the lungs. The objective was to quantify changes in airway dead space (VDaw), slope of the alveolar plateau (SLOPE) and VCO2,T as a function of MDT in healthy pigs.

Methods: Ten healthy pigs were mechanically ventilated. Airway pressure, flow and partial pressure of CO2 were recorded during resetting of the postinspiratory pause from 10% (baseline) to, in random order, 0, 5, 20 and 30% of the respiratory cycle. The immediate changes in VDaw, SLOPE, VCO2,T, and MDT after resetting were analyzed.

Results: V
Daw in percent of VT decreased from 29 to 22%, SLOPE from 0·35 to 0·16 kPa per 100 ml as MDT increased from 0·51 to 1·39 s. Over the same MDT range, VCO2,T increased by 10%. All these changes were statistically significant.

Conclusion: MDT allows comparison of different patterns of inspiration on VDaw and gas exchange. Estimation of the effects of an altered ventilator setting on exchange of CO2 can be done only after about 30 minutes, while the transient changes in VCO2,T may give immediate information. MDT affects gas exchange to an important extent. Further studies in human subjects in health and in disease are needed.
Evaluation of oxygen uptake kinetics and oxygen kinetics of peripheral skeletal muscle during recovery from exercise in patients with chronic obstructive pulmonary disease
Authors: Okamoto Takashi , Kanazawa Hiroshi , Hirata Kazuto , Yoshikawa Junichi
Published: September 2003

The biochemical features of skeletal muscle and its contribution to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD) is under active investigation. Near‐infrared spectroscopy (NIRS) can non‐invasively provide information on the oxidative capacity of muscle. To clarify whether oxygenation of peripheral muscle is one determinant of exercise tolerance, we simultaneously examined the oxygen uptake () kinetics and oxygen kinetics of peripheral skeletal muscle evaluated by NIRS during recovery from exercise in COPD patients. Fifteen patients with COPD and five normal control subjects performed a symptom‐limited incremental exercise test. On the following day, all patients performed a constant work rate exercise test while being monitored using NIRS continuously for changes in concentration of oxygenated haemoglobin (HbO2) and during expired gas analysis. We found that the time constant of during recovery from constant work rate exercise () and the time constant of HbO2 during recovery (τHbO2off) were significantly longer in COPD patients than in normal control subjects. was inversely correlated with absolute values of forced expiratory volume in 1 s (FEV1·0) and FEV1·0 (% predicted). However, no significant correlation was found between and FVC (forced vital capacity), FEV1·0/FVC, or diffusing capacity of the lung for CO (DLCO). Moreover, was inversely correlated with maximal and maximal work rate. In contrast, exhibited a significant positive correlation with τHbO2off. These results indicate that kinetics during recovery is related to re‐oxygenation of peripheral skeletal muscle evaluated by NIRS in patients with COPD. Therefore, NIRS may be a useful tool to estimate the impairment of cardiopulmonary responses and re‐oxygenation of peripheral skeletal muscle during the immediate recovery phase after exercise in COPD patients.
Cardiopulmonary alterations in mRNA expression for interleukin‐1β, the interleukin‐6 superfamily and CXC‐chemokines during development of postischaemic heart failure in the rat
Authors: Tønnessen Theis , Florholmen Geir , Henriksen Unni Lie , Christensen Geir
Published: September 2003

Cytokines and chemokines are believed to play a pathogenic role in heart failure (HF). Although some cytokines and chemokines have been examined in HF, information about others is still lacking. We aimed to examine the expression of cytokines belonging to the interleukin (IL)‐6 superfamily [IL‐6 and ciliary neurotrophic factor (CNTF)], as well as IL‐1β and the CXC‐chemokines monocyte chemoattractant protein‐1 (MCP‐1) and IL‐8. We examined their expression in the heart, lung and spleen during development of postischaemic HF 1 and 6 weeks following left coronary artery ligation. Rats, which after myocardial infarction had a left ventricular end‐diastolic pressure above 15 mmHg, were considered to be in HF. Sham‐operated rats served as controls. A substantial upregulation of cardiac IL‐1β was measured in HF at 1 week, whereas a downregulation was measured in the lungs. At 6 weeks no altered regulation was seen. CNTF was only upregulated in the viable left ventricle at 6 weeks and IL‐6 was upregulated in the infarcted region at 1 week. Cardiac MCP‐1 was upregulated in the viable and the infarcted region of the failing left ventricle at 1 week, with the highest expression in the latter. In the lung, another pattern of regulation was seen with a significant increase in pulmonary MCP‐1 at 6 weeks. IL‐8 was only detected in the infarcted region at 1 week. In the spleen, no regulation of cytokines was found. In conclusion, we report an organ‐specific regulation of cytokines and chemokines in postischaemic HF. Our novel findings of increased cardiac CNTF and cardiopulmonary MCP‐1 mRNA indicate a role for these factors in the pathogenesis of HF.
A new non‐invasive ultrasonic method for simultaneous measurements of longitudinal and radial arterial wall movements: first in vivo trial
Authors: Persson Magnus , Rydén Ahlgren Åsa , Jansson Tomas , Eriksson Anders , Persson Hans W. , Lindström Kjell
Published: September 2003

During recent years, the radial movement of the arterial wall has been extensively studied, and measurements of the radial movement are now an important tool in cardiovascular research for characterizing the mechanical properties of the arterial wall. In contrast, the longitudinal movement of vessels has gained little or no attention as it has been presumed that this movement is negligible. With modern high‐resolution ultrasound, it can, however, be seen that the intima‐media complex of the arterial wall moves not only in the radial direction, but also in the longitudinal direction during pulse‐wave propagation. This paper describes a new non‐invasive ultrasonic method that is able to measure simultaneously two dimensionally arterial vessel wall movements. The method is demonstrated in a limited in vivo trial. Results from the in vivo trial show that, apart from the well‐known radial movement, there is a distinct longitudinal movement in the human common carotid artery with, in this case, the intima‐media complex moving substantially as compared with the region of the tunica adventitia. Two‐dimensional evaluation of the vessel‐wall movements, taking not only the radial movement, but also the longitudinal movement into account, may provide novel information of importance in the evaluation of vessel‐wall function.