bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized, Double Blind Study of the Prophylactic Effect of Hyperbaric Oxygen Therapy on Migraine
Authors: Eftedal OS , Lydersen S , Helde G , White L , Brubakk AO , Stovner LJ
Published: July 2004

In a double blind, placebo-controlled study to assess the prophylactic effect of hyperbaric oxygen therapy on migraine, 40 patients were randomly assigned to a treatment group receiving three sessions of hyperbaric oxygen, or a control group receiving three hyperbaric air treatments. The patients were instructed to keep a standardized migraine diary for eight weeks before and after the treatment. Thirty-four patients completed the study. Our primary measure of efficacy was the difference between pre- and post-treatment hours of headache per week. The results show a nonsignificant reduction in hours of headache for the hyperbaric oxygen group compared to the control group. Levels of endothelin-1 in venous blood before and after treatment did not reveal any difference between the hyperbaric oxygen and control groups. We conclude that the tested protocol does not show a significant prophylactic effect on migraine and does not influence the level of endothelin-1 in venous blood.
Safety, Tolerability and Pharmacokinetics of BIBN 4096 BS, the First Selective Small Molecule Calcitonin Gene-Related Peptide Receptor Antagonist, Following Single Intravenous Administration in Healthy Volunteers
Authors: Iovino M , Feifel U , Yong C-L , Wolters J-M , Wallenstein G
Published: July 2004

BIBN 4096 BS ([R-(R∗,S∗)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl] pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide) is the first selective, highly potent, small molecule, nonpeptide calcitonin gene-related peptide (CGRP) receptor antagonist, which has been developed for the treatment of acute migraine. The objective of this study was to obtain information on the safety, tolerability and pharmacokinetics of BIBN 4096 BS following single intravenous administration of rising doses (0.1, 0.25, 0.5, 1, 2.5, 5 and 10 mg) in 55 healthy male and female volunteers. The study was of single-centre, double-blind (within dose levels), placebo-controlled, randomized, single rising dose design. Blood pressure, pulse rate, respiratory rate, ECG, laboratory tests and forearm blood flow did not reveal any clinically relevant, drug-induced changes. Sixteen adverse events (AEs) were reported by eight of 41 volunteers after BIBN 4096 BS compared to five AEs reported by four of 14 volunteers after placebo. Approximately two-thirds of all AEs related to active treatment occurred at the highest dose of 10 mg. At this dose level, all AEs were confined to the three BIBN 4096 BS-treated females, and consisted mainly of transient and mild paresthesias. Paresthesias were the single most frequent AE, whereas fatigue was the AE which occurred in the highest number of subjects. Only two AEs were of moderate intensity, all remaining AEs were of mild intensity. No serious AEs were reported. The local tolerability after intravenous administration was good. In summary, intravenously administered BIBN 4096 BS revealed a very favourable safety profile over the dose range tested in both genders. Generally well tolerated at all dose levels, it was of satisfactory tolerability in female subjects at the highest dose of 10 mg. The plasma concentration-time courses of BIBN 4096 BS showed multicompartmental disposition characteristics. Mean maximum concentration (Cmax) values appeared to be dose-proportional. Based on the results from the two high dose levels (5 and 10 mg) with sufficient individual subject data, BIBN 4096 BS exhibited a total plasma clearance (CL) of approximately 12 l/h and an apparent volume of distribution at steady state (Vss) of approximately 20 l, resulting in a terminal half-life (t1/2) of approximately 2.5 h. Inter-individual variability was moderate with a coefficient of variation of approximately 45% based on the area under the plasma concentration-time curve (AUC) values. The mean renal clearance (CLR) was approximately 2 l/h, suggesting that renal excretion plays only a minor role in the elimination of unchanged BIBN 4096 BS.
Differences of Anti-Nociceptive Mechanisms of Migraine Drugs on the Trigeminal Pain Processing during and Outside Acute Migraine Attacks
Authors: Katsarava Z , Limmroth V , Baykal O , Akguen D , Diener H-C , Kaube H
Published: July 2004

The aim of this study was to investigate central anti-nociceptive mechanisms of i.v. acetylsalicylic acid (ASA) and oral zolmitriptan (ZOL) in migraine patients and healthy subjects using the ‘nociceptive’ blink reflex (nBR). Twenty-eight migraine patients received ASA ( n = 14, 1000 mg i.v) or ZOL ( n = 14, 5 mg p.o) during the acute migraine attack and interictally. Thirty healthy subjects received either ASA or ZOL vs. placebo using a double blind cross over design. nBR was recorded in all patients and subjects before, 60 and 90 min after treatment. ASA and ZOL did not inhibit nBR responses in healthy subjects. Both ASA and ZOL suppressed nBR responses (ASA by 68%, ZOL by 78%) only during the acute attack but not interictally. The data suggest, that the anti-nociceptive effects of migraine drugs on the trigeminal nociceptive processing are different during and outside an acute migraine attack.
Interictal Lack of Habituation of Mismatch Negativity in Migraine
Authors: de Tommaso M , Guido M , Libro G , Losito L , Difruscolo O , Sardaro M , Puca F M
Published: July 2004

The aim was to study mismatch negativity features and habituation during the interictal phase of migraine. In migraine patients, a strong negative correlation has been found between the initial amplitude of long latency auditory-evoked potentials and their amplitude increase during subsequent averaging. We studied 12 outpatients with a diagnosis of migraine without aura recorded in a headache-free interval and 10 gender- and age-matched healthy volunteers not suffering from any recurrent headache. The experiment consisted of two sequential blocks of 2000 stimulations, during which 1800 (90%) recordings for standard tones and 200 (10%) for target tones were selected for averaging. The latency of the N1 component was significantly increased in migraine patients in respect of controls in both the first and second repetitions; the MMN latency was increased in the second repetition. In the control group the MMN amplitude decreased on average by 3.2 ± 1.4 μV in the second trial, whereas in migraine patients it showed a slight increase of 0.21 ± 0.11 μV in the second repetition. The MMN latency relieved in the second trial was significantly correlated with the duration of illness in the migraine patients (Spearman correlation coefficient: 0.69; P < 0.05). The increases in N1 latency and MMN latency and amplitude, the latter correlated with duration of illness, seemed to be due to a reduced anticipatory effect of stimulus repetition in migraine patients. This suggests that such hypo-activity of automatic cortical processes, subtending the discrimination of acoustic stimuli, may be a basic abnormality in migraine, developing in the course of the disease.
Epidemiological and Clinical Characteristics with Psychosocial Aspects of Tension-Type Headache in Turkish College Students
Authors: Kaynak Key FN , Donmez S , Tuzun U
Published: July 2004

We investigated the prevalence and clinical characteristics of tension-type headache (TTH), psychosocial factors contributing to the onset and aggravation of headache and coping mechanisms of individuals in a young population in Turkey. The sample consisted of 2226 university students, aged 7 to 21 years old. A self-administered questionnaire inquiring about epidemiological and clinical features of headache was filled out by participants. TTH diagnosis was determined in accordance with the International Headache Society Criteria of 1988. The prevalence of TTH was 20.35% (25.54% for women and 14.25% for men). 43.7% of headache sufferers had one or more stressful life events before the onset of headache and stress was the most frequent aggravating factor of headache (52%). Resting (58.1%) was the most common coping style. In conclusion, TTH is not a rare condition in Turkish young people and psychosocial factors are always taken into consideration for diagnosis and treatment of TTH.
Treatment of Chronic Tension-Type Headache with Botulinum Toxin: A Double-Blind, Placebo-Controlled Clinical Trial
Authors: Padberg M , de Bruijn SFTM , de Haan RJ , Tavy DLJ
Published: July 2004

Botulinum toxin is increasingly advocated as effective treatment in chronic tension-type headache. We conducted a randomized, placebo-controlled clinical trial to prove efficacy of botulinum toxin in chronic tension-type headache. Patients were randomly assigned to receive botulinum toxin (maximum 100 units) or placebo (saline) in muscles with increased tenderness. After 12 weeks there was no significant difference between the two treatment groups in decrease of headache intensity on VAS (-3.5 mm, 95% confidence interval (CI) -20 to +13), mean number of headache days (-7%; 95% CI -20 to +4), headache hours per day (-1.4%; 95% CI -3.9 to +1.1), days on which symptomatic treatment was taken (-1.9%; 95% CI -11 to +7) and number of analgesics taken per day (-0.01; 95% CI -0.25-0.22). There was no significant difference in patient's assessment of improvement after week 4, 8 and 12. Botulinum toxin was not proven effective in treatment of chronic tension-type headache. Increased muscle tenderness might not be as important in pathophysiology of chronic tension-type headache as hitherto believed.
Impaired disengagement of attention in young children with autism
Authors: Landry Reginald , Bryson Susan E.
Published: July 2004

Background: The present study examined the disengage and shift operations of visual attention in young children with autism.

Methods: For this purpose, we used a simple visual orienting task that is thought to engage attention automatically. Once attention was first engaged on a central fixation stimulus, a second stimulus was presented on either side, either simultaneously or successively. Latency to begin an eye movement to the peripheral stimulus served as the main dependent measure. The two stimulus conditions (simultaneous and successive) provided independent measures of disengaging and shifting attention, respectively. Performance of children with autism was compared to that of children with Down syndrome and a normal group.

Results: The main finding was that relative to both comparison groups, children with autism had marked difficulty in disengaging attention. Indeed, on 20% of trials they remained fixated on the first of two competing stimuli for the entire 8‐second trial duration. Evidence is also provided for a more subtle problem in executing rapid shifts of attention.

Conclusions: Our findings on disengagement in autism parallel those reported in normal 2‐month‐olds, in whom attention has been described as ‘obligatory’. Discussion focuses on the potential role of general versus domain‐specific processes in producing some of the core features of autism.
Comparison of ADHD symptom subtypes as source‐specific syndromes
Authors: Gadow Kenneth D. , Drabick Deborah A.G. , Loney Jan , Sprafkin Joyce , Salisbury Helen , Azizian Allen , Schwartz Joseph
Published: July 2004

Background:  This study examines differences between the three subtypes of attention‐deficit/hyperactivity disorder (ADHD), inattentive (I), hyperactive‐impulsive (H), and combined (C), in a heterogeneous sample of 248 boys (ages 6 to 10 years) with emotional and behavioral problems who were recruited for participation in a diagnostic study.

Method:  The boys and their mothers participated in an extensive evaluation that involved multiple assessments of cognitive, behavioral, academic, and family functioning. ADHD subtypes were defined on the basis of teacher alone, mother alone, and mother/teacher ratings of DSM‐IV symptoms.

Results:  Results indicated ADHD symptom groups showed a differential pattern of impairment socially (H,C>I) and cognitively (I,C>H). The C and H groups were the most and least impaired overall, respectively, and all subtypes were differentiated from the nonADHD clinical control or NONE (N) group in a manner consistent with the primary findings. External validation of group differences was limited, and there were marked inconsistencies in the pattern of findings depending on how groups were defined. For the most part, although the mother/teacher grouping strategy (compared with either alone) captured a greater diversity of differences between subtypes, it also obscured some.

Conclusions:  Observed findings are consistent with the notion that mothers and teachers interpret symptom statements in terms of behaviors that are most relevant for their daily concerns.
Psychopathology in female juvenile offenders
Authors: Dixon Angela , Howie Pauline , Starling Jean
Published: July 2004

Background:  The aim was to document the spectrum of present and lifetime psychological disorders in female juvenile offenders, and to examine the relations between mental health status and socio‐demographic, family and trauma variables.

Method:  One hundred juvenile offenders were matched with a comparison group of 100 females on age and socioeconomic status (SES). Psychological profiles and trauma histories of both groups were assessed using the Schedule for Affective Disorders and Schizophrenia for School‐Age Children – Present and Lifetime Version (K‐SADS‐PL) and family functioning was assessed with the Family Adaptability and Cohesion Scale II (FACES II) self‐report measure.

Results:  Rates of psychopathology were higher for offenders than non‐offenders (p < .001), with particularly high levels of conduct disorder (91% v.1%, p < .001), substance abuse disorders (85% v. 5%, p < .001), depression (55% v. 25%, p < .001) and posttraumatic stress disorder (37% v. 4%, p < .001). In the offenders, 78% met the criteria for three or more diagnoses. The number of psychiatric diagnoses was the most significant factor associated with offender status (OR = 21.26, p < .001).

Conclusions:  There is a high prevalence of psychological disorder in females in juvenile justice custody and this has a very strong association with offender status. Because these co‐morbid disorders are treatable, there is a clear opportunity to intervene to decrease psychological distress.
The prediction of disruptive behaviour disorders in an urban community sample: the contribution of person‐centred analyses
Authors: Burt Keith B. , Hay Dale F. , Pawlby Susan , Harold Gordon , Sharp Deborah
Published: July 2004

Background:  Variable‐ and person‐centred analyses were used to examine prediction of middle childhood behaviour problems from earlier child and family measures.

Method:  A community sample of 164 families, initially recruited at antenatal clinics at two South London practices, was assessed for children's behaviour problems and cognitive ability, maternal mental health, and the family environment when the children were 4 years old. At age 11, children, mothers, and teachers reported the child's disruptive behaviour, and mothers and children were interviewed to identify cases of disruptive behaviour disorders (DBD).

Results:  Neither social class nor ethnicity predicted the child's disruptive behaviour at age 11. Rather, path analyses and logistic regression analyses drew attention to early behavioural problems, maternal mental health and the child's cognitive ability at 4 as predictors of disruptive behaviour at age 11. Cluster analysis extended these findings by identifying two distinct pathways to disruptive symptoms and disorder. In one subgroup children who showed intellectual difficulties at 4 had become disruptive by 11. In a second subgroup mothers and children both showed psychological problems when the child was 4, and the children were disruptive at age 11. The person‐centred approach also revealed a high‐functioning group of cognitively able 4‐year‐olds in supportive environments, at especially low risk for DBD.

Conclusions:  Combining variable‐ and person‐centred analytic approaches can aid prediction of children's problems, draw attention to pertinent developmental pathways, and help integrate data from multiple informants.
Parent–child dyadic mutuality and child behavior problems: an investigation of gene–environment processes
Authors: Deater‐Deckard Kirby , Petrill Stephen A.
Published: July 2004

Background: Parent–child mutuality is comprised of emotional reciprocity, co‐responsiveness, and cooperation, which together represent aspects of co‐regulation of emotion and behavior that may be important in the etiology of children's behavior problems. Furthermore, individual differences in children's mutuality and behavior problems involve transactions between genetic and environmental influences. Behavioral genetic designs are useful for elucidating these processes.

Methods: The sample included 396 children in adoptive families (53% female, ageM = 8.16 years), of whom 244 were siblings (122 pairs). All of the siblings were genetically unrelated. In some families, one child was adopted but the other child was a biological child of the adoptive parents. We observed mother–child dyadic mutuality (a composite score including responsiveness, interaction reciprocity, and cooperation) during videotaped in‐home observations. In addition, child behavior problems were assessed and represented as a composite score including observers’ ratings of noncompliance, and parents’ ratings of aggression and conduct problems.

Results: Greater mutuality was associated with lower levels of child behavior problems, both between families and within families (i.e., sibling differences). The sibling intra‐class correlation for mutuality with the same parent was near zero in this sample of genetically unrelated siblings. The correlation between child behavior problems and dyadic mutuality did not vary as a function of mother–child genetic similarity.

Conclusions: Mother–child mutuality is child specific within families, a finding that is consistent with theories regarding bi‐directional parent and child effects in socialization. In addition, there was no evidence of passive gene–environment correlation, suggesting that the link between lower levels of maternal mutuality and higher levels of childbehavior problems is not only reflecting overlapping genetic influences on parent and child behavior.
Annotation: Deconstructing the attention deficit in fragile X syndrome: a developmental neuropsychological approach
Authors: Cornish K.M. , Turk J. , Wilding J. , Sudhalter V. , Munir F. , Kooy F. , Hagerman R.
Published: July 2004

Background: Fragile X syndrome is one of the world's leading hereditary causes of developmental delay in males. The past decade has witnessed an explosion of research that has begun to unravel the condition at its various levels: from the genetic and brain levels to the cognitive level, and then to the environmental and behavioural levels. Our aim in this review is to attempt to integrate some of the extensive body of knowledge to move the research a step closer to understanding how the dynamics of atypical development can influence the specific cognitive and behavioural end‐states frequently observed in children and adolescents with fragile X syndrome.

Methods: We conducted a review of the current neuropsychological and neuropsychiatric approaches that have attempted to delineate the pattern of ‘spared’ and ‘impaired’ functions associated with the phenotype.

Results: The profile of findings suggests that fragile X syndrome should not be viewed merely as a catalogue of spared and impaired cognitive functions or modules. Instead, there appears to be a process of almost gradual modularisation whereby cognitive mechanisms become domain specific as a function of development itself (Karmiloff‐Smith, 1992). The results of a decade of intense research point towards an early weakness in one or more components of executive control rather than single, static higher‐level deficits (e.g., spatial cognition, speech processing). This weakness affects both the development of more complex functions and current performance.

Conclusions: The prevailing tendency to interpret developmental disorders in terms of fixed damage to distinct modular functions needs to be reconsidered. We offer this review as an example of an alternative approach, attempting to identify an initial deficit and its consequences for the course of development. Through better definition of the cognitive and behavioural phenotype, in combination with current progress in brain imaging techniques and molecular studies, the next decade should continue to hold exciting promise for fragile X syndrome and other neurodevelopmental disorders.
Effects of music therapy for children and adolescents with psychopathology: a meta‐analysis
Authors: Gold Christian , Voracek Martin , Wigram Tony
Published: July 2004

Background:  The objectives of this review were to examine the overall efficacy of music therapy for children and adolescents with psychopathology, and to examine how the size of the effect of music therapy is influenced by the type of pathology, client's age, music therapy approach, and type of outcome.

Method:  Eleven studies were included for analysis, which resulted in a total of 188 subjects for the meta‐analysis. Effect sizes from these studies were combined, with weighting for sample size, and their distribution was examined.

Results:  After exclusion of an extreme positive outlying value, the analysis revealed that music therapy has a medium to large positive effect (ES = .61) on clinically relevant outcomes that was statistically highly significant (p < .001) and statistically homogeneous. No evidence of a publication bias was identified. Effects tended to be greater for behavioural and developmental disorders than for emotional disorders; greater for eclectic, psychodynamic, and humanistic approaches than for behavioural models; and greater for behavioural and developmental outcomes than for social skills and self‐concept.

Conclusions:  Implications for clinical practice and research are discussed.
Postpartum maternal moods and infant size predict performance on a national high school entrance examination
Authors: Galler Janina R. , Ramsey Frank C. , Harrison Robert H. , Taylor John , Cumberbatch Glenroy , Forde Victor
Published: July 2004

Background: In an earlier series of studies, we documented the effects of feeding practices and postnatal maternal mood on the growth and development of 226 Barbadian children during the first few months of life. In this report, we extend our earlier studies by examining predictive relationships between infant size, feeding practices and postpartum maternal moods and scores on a national high school examination, the Common Entrance Examination (CEE), at 11 to 12 years of age.

Methods: Feeding practices, anthropometry, and maternal moods, using Zung depression and anxiety scales and a morale scale, were assessed at 7 weeks (n = 158), 3 months (n = 168), and 6 months (n = 209) postpartum. Background variables including sociodemographic and home environmental factors were also assessed during infancy. CEE scores on 169 of the children in the original study were obtained from the Ministry of Education of Barbados.

Results: In our sample of 86 boys and 83 girls, we found that reduced infant lengths and weights at 3 and 6 months of age were predictive of lower CEE, especially math scores. Children who were smaller at these early ages had significantly lower scores on the examination than did larger children. Postpartum maternal moods, including reports of despair and anxiety, were also found to be significant predictors of lower CEE scores, especially English scores. However, breast‐feeding and other feeding practices were not directly associated with the CEE scores. Background variables, which significantly predicted lower CEE scores, included young maternal age at the time of her first pregnancy, more children in the home, less maternal education, and fewer home conveniences. Significant associations between infant anthropometry, maternal moods and CEE scores were all significant even when these background variables were controlled for.

Conclusions: These findings have important implications for developing interventions early in life to improve academic test scores and future opportunities available to children in this setting.
Cognitive appraisals in young people with obsessive‐compulsive disorder
Authors: Libby Sarah , Reynolds Shirley , Derisley Jo , Clark Sarah
Published: July 2004

Background:  A number of cognitive appraisals have been identified as important in the manifestation of obsessive‐compulsive disorder (OCD) in adults. There have, however, been few attempts to explore these cognitive appraisals in clinical groups of young people.

Method:  This study compared young people aged between 11 and 18 years with OCD (N = 28), young people with other types of anxiety disorders (N = 28) and a non‐clinical group (N = 62) on three questionnaire measures of cognitive appraisals. These were inflated responsibility (Responsibility Attitude Scale; Salkovskis et al., 2000), thought–action fusion – likelihood other (Thought–Action Fusion Scale; Shafran, Thordarson & Rachman, 1996) and perfectionism (Multidimensional Perfectionism Scale; Frost, Marten, Luhart & Rosenblate, 1990).

Results:  The young people with OCD had significantly higher scores on inflated responsibility, thought–action fusion – (likelihood other), and one aspect of perfectionism, concern over mistakes, than the other groups. In addition, inflated responsibility independently predicted OCD symptom severity.

Conclusions:  The results generally support a downward extension of the cognitive appraisals held by adults with OCD to young people with the disorder. Some of the results, however, raise issues about potential developmental shifts in cognitive appraisals. The findings are discussed in relation to implications for the cognitive model of OCD and cognitive behavioural therapy for young people with OCD.
Contributions of phonological memory, language comprehension and hearing to the expressive language of adolescents and young adults with Down syndrome
Authors: Laws Glynis
Published: July 2004

Background: Expressive language constitutes a major challenge to the development of individuals with Down syndrome. This paper investigates the relationships between expressive language abilities, language comprehension and the deficits in verbal short‐term memory and hearing which are also associated with the syndrome.

Methods: Tests of nonverbal ability, expressive language, verbal short‐term memory, visuo‐spatial memory, language comprehension and hearing were administered.

Results: Phonological memory, measured by nonword repetition, was significantly correlated with expressive language abilities measured by MLU and sentence recall. Adjusting for word repetition skills did not reduce this correlation, suggesting that the relationship did not depend on the fact that both tests required spoken output. Hearing did not contribute significantly to expressive language scores of participants who provided an intelligible narrative. However, level of hearing loss as well as other language and memory measures did differentiate these participants from those who were unable to produce an intelligible narrative.

Conclusion: Phonological memory was closely associated with the expressive language abilities of individuals with Down syndrome. Hearing loss appeared to be less closely related except that individuals with uncorrected mild to moderate hearing loss had difficulty with the narrative task. Further research is necessary to establish the nature of these relationships.
Theory‐of‐mind development in oral deaf children with cochlear implants or conventional hearing aids
Authors: Peterson Candida C.
Published: July 2004

Background: In the context of the established finding that theory‐of‐mind (ToM) growth is seriously delayed in late‐signing deaf children, and some evidence of equivalent delays in those learning speech with conventional hearing aids, this study's novel contribution was to explore ToM development in deaf children with cochlear implants. Implants can substantially boost auditory acuity and rates of language growth. Despite the implant, there are often problems socialising with hearing peers and some language difficulties, lending special theoretical interest to the present comparative design.

Methods: A total of 52 children aged 4 to 12 years took a battery of false belief tests of ToM. There were 26 oral deaf children, half with implants and half with hearing aids, evenly divided between oral‐only versus sign‐plus‐oral schools. Comparison groups of age‐matched high‐functioning children with autism and younger hearing children were also included.

Results: No significant ToM differences emerged between deaf children with implants and those with hearing aids, nor between those in oral‐only versus sign‐plus‐oral schools. Nor did the deaf children perform any better on the ToM tasks than their age peers with autism. Hearing preschoolers scored significantly higher than all other groups. For the deaf and the autistic children, as well as the preschoolers, rate of language development and verbal maturity significantly predicted variability in ToM, over and above chronological age.

Conclusions: The finding that deaf children with cochlear implants are as delayed in ToM development as children with autism and their deaf peers with hearing aids or late sign language highlights the likely significance of peer interaction and early fluent communication with peers and family, whether in sign or in speech, in order to optimally facilitate the growth of social cognition and language.
Speech‐in‐noise perception in high‐functioning individuals with autism or Asperger's syndrome
Authors: Alcántara José I. , Weisblatt Emma J.L. , Moore Brian C.J. , Bolton Patrick F.
Published: July 2004

Background:  High‐functioning individuals with autism (HFA) or Asperger's syndrome (AS) commonly report difficulties understanding speech in situations where there is background speech or noise. The objective of this study was threefold: (1) to verify the validity of these reports; (2) to quantify the difficulties experienced; and (3) to propose possible mechanisms to explain the perceptual deficits described.

Method:  Speech‐in‐noise perception abilities were measured using speech reception thresholds (SRTs), defined as the speech‐to‐noise ratio (SNR) at which approximately 50% of the speech is correctly identified. SRTs were measured for 11 individuals with HFA/AS and 9 age/IQ‐matched normal‐hearing control subjects, using an adaptive procedure, in a non‐reverberant sound‐attenuating chamber. The speech materials were standardised lists of everyday sentences spoken by a British male speaker. The background sounds were: (1) a single female talker; (2) a steady speech‐shaped noise; (3) a speech‐shaped noise with temporal dips; (4) a steady speech‐shaped noise with regularly spaced spectral dips; and (5) a speech‐shaped noise with temporal and spectral dips.

Results:  SRTs for the HFA/AS group were generally higher (worse) than those for the controls, across the five background sounds. A statistically significant difference in SRTs between the subject groups was found only for those background sounds that contained temporal or spectro‐temporal dips. SRTs for the HFA/AS individuals were 2 to 3.5 dB higher than for the controls, equivalent to a substantial decrease in speech recognition. Expressed another way, the HFA/AS individuals required a higher SNR, whenever there were temporal dips in the background sound, to perform at the same level as the controls.

Conclusions:  The results suggest that the speech‐in‐noise perception difficulties experienced by individuals with autism may be due, in part, to a reduced ability to integrate information from glimpses present in the temporal dips in the noise.
Autism and attachment: a meta‐analytic review
Authors: Rutgers Anna H. , Bakermans‐Kranenburg Marian J. , van Ijzendoorn Marinus H. , van Berckelaer‐Onnes Ina A.
Published: July 2004

Method:  Sixteen studies on attachment in children with autism were reviewed, and ten studies with data on observed attachment security (N = 287) were included in a quantitative meta‐analysis.

Results:  Despite the impairments of children with autism in reciprocal social interaction, the majority of the studies found evidence for attachment behaviours in these children. In four samples using the Strange Situation procedure the average percentage of secure attachments amounted to 53% (n = 72). Meta‐analytic results showed that children with autism were significantly less securely attached to their parents than comparison children, and the combined effect size for this difference was moderate (r = .24). Children with autism displayed less attachment security than comparisons without autism, but this difference disappeared in samples with children with higher mental development, and in samples in which autism was mixed with less severe symptoms of autistic spectrum disorders.

Conclusions:  It is concluded that attachment security is compatible with autism, and can be assessed with Strange Situation type of procedures. The co‐morbidity of autism and mental retardation appears to be associated with attachment insecurity.
Rapid Report
Authors: Miller P. , Kemp P. J. , Lewis A. , Chapman C. G. , Meadows H. J. , Peers C.
Published: July 2004

The human tandem P domain K+ channel hTREK‐1 (KCNK2) is distributed widely through the CNS. Here, whole‐cell patch clamp recordings were employed to investigate the effects of hypoxia on hTREK‐1 channels stably expressed in human embryonic kidney cells. Acute hypoxia caused a rapid and reversible inhibition of whole‐cell K+ current amplitudes; this was PO2 dependent with a maximal inhibition achieved at 60 mmHg and below. In accordance with previous studies, hTREK‐1 current amplitudes were enhanced by arachidonic acid. This effect was concentration dependent, with maximal enhancement observed at a concentration of 10 μm. Membrane deformation by the crenator trinitrophenol (to mimic cell swelling) or the cup former chlorpromazine (to mimic cell shrinkage) caused robust activation and inhibition of currents, respectively. However, current augmentation by either arachidonic acid or trinitrophenol was completely prevented during hypoxia; conversely, hypoxia blunted the inhibitory action of chlorpromazine. The abilities of arachidonic acid to augment currents and of hypoxia to completely abrogate this effect were also observed in cell‐attached patches. Our data indicate that hypoxia interacts with hTREK‐1, and occludes its modulation by arachidonic acid and membrane deformation. These findings also suggest that the potential neuroprotective role of TREK channels, which has recently been proposed, requires reconsideration since hTREK‐1 activation is unlikely when ambient PO2 is below 60 mmHg ‐ a situation which normally pertains in the CNS even during systemic normoxia.
Topical Review
Authors: Eckberg Dwain L.
Published: July 2004

Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this ‘respiratory gating’ is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R–R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R–R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.
Rapid Report
Authors: Maljevic Snezana , Lerche Christian , Seebohm Guiscard , Alekov Alexi K. , Busch Andreas E. , Lerche Holger
Published: July 2004

Coexpression of KCNQ2 and KCNQ3 channels results in a 10‐fold increased current amplitude compared to that of KCNQ2 alone, suggesting the formation of heteromultimeric channels. There is no interaction of either channel with KCNQ1. We evaluated the C‐terminus as a potential interaction domain by construction of chimeras with interchanged C‐termini of KCNQ1, KCNQ2 and KCNQ3 and functional expression in Xenopus oocytes. The chimera of KCNQ1 with a KCNQ2 C‐terminus (Q1ctQ2) showed an 8‐fold increase in current amplitude, and Q1ctQ3 a 3‐fold increase when coexpressed with KCNQ3 and KCNQ2, respectively, indicating that the C‐terminus contains an interaction domain. To characterize this interacting region, we studied further chimeras of KCNQ1 containing different parts of the KCNQ3 C‐terminus for interaction with KCNQ2. We also evaluated short sequences of the KCNQ2 C‐terminus for a dominant‐negative effect on Q1ctQ3. According to the results of these experiments, functional interaction of KCNQ2 and KCNQ3 requires a highly conserved region of about 80 amino acids, previously called the A‐domain, plus either 40 residues downstream of the A‐domain (B‐domain) or the proximal C‐terminus between S6 and the A‐domain. Furthermore, the chimeras Q1ctQ3 and Q2ctQ3 showed > 10‐fold increased current amplitudes compared to KCNQ1 or KCNQ2 alone and a strong depolarizing shift of voltage‐dependent activation. The proximal part of the KCNQ3 C‐terminus was necessary to produce these effects. Our results indicate that specific parts of the C‐terminus enable the interaction between KCNQ2 and KCNQ3 channels and that different parts of the KCNQ3 C‐terminus are important for regulating current amplitude.
Presence of (phospho)creatine in developing and adult skeletal muscle of mice without mitochondrial and cytosolic muscle creatine kinase isoforms
Authors: 't Zandt H. J. A. in , de Groof A. J. C. , Renema W. K. J. , Oerlemans F. T. J. J. , Klomp D. W. J. , Wieringa B. , Heerschap A.
Published: July 2004

We assessed the relationship between phosphocreatine (PCr) and creatine (Cr) content and creatine kinase (CK) activity in skeletal muscle of mice. The PCr and total Cr (tCr) concentrations, as well as CK activity, in hindlimb muscles of mice, with or without the cytosolic and mitochondrial isoforms of muscle creatine kinase (wild‐type or CK–/– mice), were determined by in vivo magnetic resonance (MR) spectroscopy and by biochemical means during postnatal growth and adulthood. In wild‐type muscle the [tCr], PCr/ATP ratio and CK activity increased rapidly in the first 4–7 weeks. Remarkably, CK–/– mice showed a similar increase in the PCr/ATP ratio during the first month in the presence of only minor brain‐type BB‐CK activity. Uptake of Cr in muscle was seemingly unrelated to CK activity as tCr increased in the same way in the muscles of both mouse types. At older ages the PCr/ATP ratio decreased in CK–/– muscles, in contrast to wild‐type where it still slowly increased, whereas [tCr] was similar for muscle of both mouse types. Using a new in vivo MR approach with application of [4‐13C]Cr, a lower PCr/tCr ratio was also observed in CK–/– muscle. From these data it follows that in vivo global ATP levels at rest are similar in the presence or absence of CK. Although Cr could still be converted to PCr in mature CK–/– muscle, the immediate availability of PCr decreased, and PCr became partly inconvertible at older ages. Apparently, catalysis of the CK reaction by BB‐CK, although significant in muscles of newborn mice, gradually declines to very low levels in adulthood. Part or all of this BB‐CK may arise from satellite cells fusing with myotubes, a process that is most active during the first months of life. Finally, our observation that the MR and chemical assessment of muscle [tCr] and PCr/tCr ratio were similar for all mice does not support the existence of a significant MR‐invisible or immobile pool of Cr, with a role for CK in this phenomenon.
Rapid Report
Authors: Manto Mario‐Ubaldo , Bosse Pierre
Published: July 2004

So far, there is only one procedure known to increase hypermetria in cerebellar patients. Facing an increased inertia of the moving limb, patients presenting a lesion of the lateral cerebellum are able to increase appropriately the intensity of the agonist electromyographic (EMG) activity (the launching force), but are unable to adapt the intensity of the antagonist activity (the braking force). As a result, hypermetria is larger when the inertial load is artificially increased. Recent studies have demonstrated that hyperventilation increases hypermetria in patients presenting a spinocerebellar ataxia type 6 (SCA 6), a disorder associated with polyglutamine expansions in the α1A‐voltage‐dependent calcium channel. The mechanism of this increase of hypermetria has not been identified so far. In the present work, we combined kinematic, EMG and transcranial Doppler studies to understand the effects of hyperventilation on fast goal‐directed movements in patients presenting a SCA 6. Both in the normal mechanical state and after increasing the inertial load of the moving hand, hyperventilation induced an increase of hypermetria. Hyperventilation increased the delay of the onset latency of the antagonist EMG activity and decreased the rate of rise of both the agonist and the antagonist EMG activities. Hyperventilation induced a marked decrease in cerebral blood flow velocities. The mechanism of this provocative test is original and is distinct from the mechanism of the load‐induced increase of hypermetria.
Mechanisms of the cerebrovascular response to apnoea in humans
Authors: Przyby?owski Tadeusz , Bangash Muhammad‐Fuad , Reichmuth Kevin , Morgan Barbara J. , Skatrud James B. , Dempsey Jerome A.
Published: July 2004

We measured ventilation, arterial O2 saturation, end‐tidal CO2 (PET,CO2), blood pressure (intra‐arterial catheter or photoelectric plethysmograph), and flow velocity in the middle cerebral artery (CFV) (pulsed Doppler ultrasound) in 17 healthy awake subjects while they performed 20 s breath holds under control conditions and during ganglionic blockade (intravenous trimethaphan, 4.4 ± 1.1 mg min−1 (mean ±s.d.)). Under control conditions, breath holding caused increases in PET,CO2 (7 ± 1 mmHg) and in mean arterial pressure (MAP) (15 ± 2 mmHg). A transient hyperventilation (PET,CO2−7 ± 1 mmHg vs. baseline) occurred post‐apnoea. CFV increased during apnoeas (by 42 ± 3 %) and decreased below baseline (by 20 ± 2 %) during post‐apnoea hyperventilation. In the post‐apnoea recovery period, CFV returned to baseline in 45 ± 4 s. The post‐apnoea decrease in CFV did not occur when hyperventilation was prevented. During ganglionic blockade, which abolished the increase in MAP, apnoea‐induced increases in CFV were partially attenuated (by 26 ± 2 %). Increases in PET,CO2 and decreases in oxyhaemoglobin saturation (Sa,O2) (by 2 ± 1 %) during breath holds were identical in the intact and blocked conditions. Ganglionic blockade had no effect on the slope of the CFV response to hypocapnia but it reduced the CFV response to hypercapnia (by 17 ± 5 %). We attribute this effect to abolition of the hypercapnia‐induced increase in MAP. Peak increases in CFV during 20 s Mueller manoeuvres (40 ± 3 %) were the same as control breath holds, despite a 15 mmHg initial, transient decrease in MAP. Hyperoxia also had no effect on the apnoea‐induced increase in CFV (40 ± 4 %). We conclude that apnoea‐induced fluctuations in CFV were caused primarily by increases and decreases in arterial partial pressure of CO2 (Pa,CO2) and that sympathetic nervous system activity was not required for either the initiation or the maintenance of the cerebrovascular response to hyper‐ and hypocapnia. Increased MAP or other unknown influences of autonomic activation on the cerebral circulation played a smaller but significant role in the apnoea‐induced increase in CFV; however, negative intrathoracic pressure and the small amount of oxyhaemoglobin desaturation caused by 20 s apnoea did not affect CFV.
Effects of Provider Practice on Functional Independence in Older Adults
Authors: Phelan Elizabeth A. , Williams Barbara , LaCroix Andrea Z. , Grothaus Lou , LoGerfo James P. , Wagner Edward H.
Published: July 2004

Objectives: To examine provider determinants of new‐onset disability in basic activities of daily living (ADLs) in community‐dwelling elderly.

Design: Observational study.

Setting: King County, Washington.

Participants: A random sample of 800 health maintenance organization (HMO) enrollees aged 65 and older participating in a prospective longitudinal cohort study of dementia and normal aging and their 56 primary care providers formed the study population.

Measurements: Incident ADL disability, defined as any new onset of difficulty performing any of the basic ADLs at follow‐up assessments, was examined in relation to provider characteristics and practice style using logistic regression and adjusting for case‐mix, patient and provider factors associated with ADL disability, and clustering by provider.

Results: Neither provider experience taking care of large numbers of elderly patients nor having a certificate of added qualifications in geriatrics was associated with patient ADL disability at 2 or 4 years of follow‐up (adjusted odds ratio (AOR) for experience=1.29, 95% confidence interval (CI)=0.81–2.05; AOR for added qualifications=0.72, 95% CI=0.38–1.39; results at 4 years analogous). A practice style embodying traditional geriatric principles of care was not associated with a reduced likelihood of ADL disability over 4 years of follow‐up (AOR for prescribing no high‐risk medications=0.56, 95% CI=0.16–1.94; AOR for managing geriatric syndromes=0.94, 95% CI=0.40–2.19; AOR for a team care approach=1.35, 95% CI=0.66–2.75).

Conclusion: Taking care of a large number of elderly patients, obtaining a certificate of added qualifications in geriatrics, and practicing with a traditional geriatric orientation do not appear to influence the development of ADL disability in elder, community dwelling HMO enrollees.