Vestibular and oculomotor function in children with CP: Descriptive study.

OBJECTIVE: We aimed to describe vestibular/oculomotor function of 7-12-year-old children with CP, Gross Motor Function Classification System (GMFCS) levels (I-III), in comparison to an age-matched control group to understand the effect of the vestibular system on activities and participation of children with CP. METHODS: Vestibular, oculomotor and balance function were tested in children with CP. Central and peripheral vestibular function was examined using an enclosed rotary chair and infrared video goggles (100 Hz) that measured eye movements. Oculomotor tests included smooth pursuit and optokinetic nystagmus (OKN). Vestibulo-Ocular Reflex (VOR) tests, done in complete darkness, included step rotation (STEP), sinusoidal harmonic acceleration (SHA) test, VOR cancellation and enhancement, and subjective visual vertical and horizontal (SVV/SVH). The integrity of the saccule was tested with the Cervical Vestibular Evoked Myogenic Potential. If able, the participants' balance abilities were examined using the Sensory Organization Test (SOT) to determine ability to maintain standing balance during six conditions that challenged the visual, somatosensory and vestibular systems. Independent t-tests and Mann-Whitney U tests were used to compare results between groups. RESULTS: Forty-one children with CP (mean age = 9.44 years, SD = 1.66; 23F/18M; Gross Motor Function Classification System levels: I (n = 19), II (n = 7), III (n = 15) and thirty-three typically developing (TD) children (mean age = 10.16 years, SD = 1.6; 13F/20M) were recruited from the Birmingham, AL community. There was no significant difference between children with CP and TD children in saccular function (i.e. C-VEMP test), and peripheral vestibular end organ (i.e. SHA test and STEP test), VOR enhancement, or OKN gain. Velocity gain for horizontal smooth pursuit was significantly worse in children with CP (p = 0.009), compared to TD children. Poor mediation of central vestibular function were that evident with significantly higher VOR cancellation gain in children with CP (p < 0.0001), compared to TD children and significantly higher SVV variance (p = 0.002), SVH mean (p = 0.001), and SVH variance (p < 0.0001) in children with CP compared to TD children. Compromised balance abilities in children with CP was evident with significantly lower composite scores (p < 0.0001), vestibular ratio (p < 0.0001), and visual ratio (p = 0.021). The somatosensory ratio (p = 0.798) of children with CP was similar to children with TD. CONCLUSIONS: Although peripheral vestibular function was intact, children with CP had difficulty coupling eye and head movement (VOR cancellation), using the vestibular system for postural control (SOT), demonstrated poor perception of upright (SVV/SVH), and had difficulty following a slow moving target (smooth pursuit eye movement). These results implicate a central vestibular and oculomotor function impairment the severity of which corresponded with severity of the level of CP.

FAANG, establishing metadata standards, validation and best practices for the farmed and companion animal community.

The Functional Annotation of ANimal Genomes (FAANG) project aims, through a coordinated international effort, to provide high quality functional annotation of animal genomes with an initial focus on farmed and companion animals. A key goal of the initiative is to ensure high quality and rich supporting metadata to describe the project's animals, specimens, cell cultures and experimental assays. By defining rich sample and experimental metadata standards and promoting best practices in data descriptions, deposition and openness, FAANG champions higher quality and reusability of published datasets. FAANG has established a Data Coordination Centre, which sits at the heart of the Metadata and Data Sharing Committee. It continues to evolve the metadata standards, support submissions and, crucially, create powerful and accessible tools to support deposition and validation of metadata. FAANG conforms to the findable, accessible, interoperable, and reusable (FAIR) data principles, with high quality, open access and functionally interlinked data. In addition to data generated by FAANG members and specific FAANG projects, existing datasets that meet the main-or more permissive legacy-standards are incorporated into a central, focused, functional data resource portal for the entire farmed and companion animal community. Through clear and effective metadata standards, validation and conversion software, combined with promotion of best practices in metadata implementation, FAANG aims to maximise effectiveness and inter-comparability of assay data. This supports the community to create a rich genome-to-phenotype resource and promotes continuing improvements in animal data standards as a whole.

Investigation of health perspectives of those with physical disabilities: the role of spirituality as a determinant of health.

PURPOSE: To identify key determinants of health and the process of health attainment for people with musculoskeletal disabilities. METHOD: Focus groups of people with musculoskeletal disorders, including 30 members and their five trained facilitators, provided data. Discussed were 'What is health for you?' and 'What has helped, or would help you achieve this health?' Delphi-structured analysis identified health themes and a health process model was developed with the facilitators comprising the expert panel. RESULTS: Health was perceived as centred on relationships that required a spiritual awareness for a strong and resilient identity. The Self Attributes Model developed portrays the processes perceived to be required for health. CONCLUSIONS: Although physical, social and psychological interventions are essential aspects of health intervention, by themselves they are not sufficient. Also required for health is a strong resilient self resulting from interaction and connection with other people and the natural world. Moreover, development of such an identity requires a spiritual world-view comprising an acknowledgement of the essence of self and focus upon the nature of the connection of this essence with all other aspects of life. Further research is required to advance understanding of the process by which this occurs for people with chronic disorders.

Molecular basis of amplification in Drosophila phototransduction: roles for G protein, phospholipase C, and diacylglycerol kinase.

In Drosophila photoreceptors, the amplification responsible for generating quantum bumps in response to photoisomerization of single rhodopsin molecules has been thought to be mediated downstream of phospholipase C (PLC), since bump amplitudes were reportedly unaffected in mutants with greatly reduced levels of either G protein or PLC. We now find that quantum bumps in such mutants are reduced approximately 3- to 5-fold but are restored to near wild-type values by mutations in the rdgA gene encoding diacylglycerol kinase (DGK) and also by depleting intracellular ATP. The results demonstrate that amplification requires activation of multiple G protein and PLC molecules, identify DGK as a key enzyme regulating amplification, and implicate diacylglycerol as a messenger of excitation in Drosophila phototransduction.

Psychological disorder in asthma is associated with poor control and poor adherence to inhaled steroids.

Previous studies have linked psychological morbidity to poor control of asthma, but have not objectively measured adherence to treatment, and have linked poor adherence to depression, but have not measured asthma severity. This study assessed asthma and psychological morbidity and objectively measured adherence to medication and showed that psychological morbidity in those with asthma is significantly increased when control of asthma is poor, especially when control is poor and adherence to inhaled steroid regimen is low.

Compliance in asthma.

Low rates of compliance with medication pose a major challenge to the effective management of most chronic diseases, including asthma. The high medical and social costs of non-compliance, and the apparent lack of effective methods for dealing with it, has stimulated renewed interest in this complex issue. Two broad categories of non-compliance have been identified, namely unintentional (or 'accidental') and intentional (or 'deliberate'). Unintentional non-compliance may result from poor doctor-patient communication or a lack of ability to follow advice. Intentional non-compliance occurs when the patient knows what is required but decides not to follow this to some degree. Healthcare professionals need to be aware of the various issues affecting compliance in all patients. The reasons for non-compliance are many and varied, and include factors such as complexity of the treatment regimen, administration route, patient beliefs about therapy and other psychological factors. Improvement in patient compliance with therapy will require better doctor-patient communication, improved patient education, the tailoring of therapy to the individual and possible novel strategies such as offering feedback to the patients on their level of compliance.

Evaluation of an electronic hand-held spirometer in patients with asthma.

In this pilot study we assessed patient compliance and acceptability of data recorded in the home environment by asthmatics using a Vitalograph 2110 spirometer which measures peak expiratory flow rate (PEFR) and forced expiratory volume in 1 s (FEV1). This meter automatically time and date stamps all measurements and can also assess the technical acceptability of results. Data are uploaded to a personal computer for review and analysis. We recruited 30 patients (10 male and 20 female, age range 21-72 years) from the chest clinic at Guy's Hospital (n = 20) and from a GP clinic (n = 10). Patients were asked to record spirometry data using the meter at set times (8.00 a.m. and 8.00 p.m.) for 2 weeks. The spirometer incorporated an alarm to remind patients to take measurements. All patients completed the study. Mean (SD) compliance with spirometer use was 100.8% (49.9%). Nineteen patients had a compliance rate of between 80% and 120% of expected use. Timing of recordings was compared with the scheduled times of 8.00 a.m. and 8.00 p.m. Values recorded with +/- 2 h were judged as acceptable. For morning recordings 67.4% of all values and for evening recordings 71.7% of all values met this criterion. Technical acceptability of spirometry data was also assessed by using quality assurance criteria recorded by the spirometer. Valid tests were performed for 75.2% of all recordings. Twenty-two patients performed valid tests for 80-100% of the time. We suggest that the use of an electronic meter in the home environment is practical and is likely to generate more accurate and reliable data.

Single centre open study to compare patient recording of PRN salbutamol use on a daily diary card with actual use as recorded by the MDI compliance monitor.

The aim of this study was to assess the patients' use of inhaled short acting bronchodilators as rescue therapy during a 4-week study period. In this study an electronic metered-dose inhaler compliance monitor (MDI-CM) was used to measure the time and date of actuations of the device and this information was then compared with the patients' self reporting diary card (DC). Salbutamol canisters were used in the compliance monitor. The study was approved by the local ethics committee, and written informed consent was obtained from all patients. Patients aged 18 years and over who were either receiving, or in the investigators opinion required, inhaled salbutamol on a PRN basis were enrolled for a 4-week monitoring phase during which all rescue salbutamol used was obtained from the MDI-CM. Patients were recording their use of salbutamol in the DC each morning and evening. There was a 2-week follow-up period following completion of the monitoring phase or withdrawal from the study. Forty-four patients were enrolled and 35 patients completed the study. The mean age (range) was 43 (20-76) years and mean FEV1 2.32 (0.7-4.0) 1, with male:female ratio of 19:25. Comparison of MDI-CM and DC recordings showed patients fell into three categories: (1) patients who used rescue salbutamol appropriately and whose MDI-CM and DC recordings matched closely; (2) patients who used rescue salbutamol for acute relief but whose MDI-CM and DC recordings did not correlate and (3) patients whose use of rescue salbutamol was inappropriate or erratic according to the MDI-CM but whose DC indicated good compliance. This category of patients include those who 'dumped' all their salbutamol before attending clinic appointments. There was no significant difference in the demographic details or the severity of disease in the three groups. Recorded use of 'rescue' bronchodilator is frequently used as an indicator of efficacy for new anti-asthma therapies. This study comparing electronic data monitoring and remembered rescue salbutamol highlights the potential errors that can occur without accurate recording systems.

Home nebulized therapy for patients with COPD: patient compliance with treatment and its relation to quality of life.

STUDY OBJECTIVES: To assess compliance with home nebulized therapy in patients with COPD. DESIGN: Patients' home nebulizers were replaced with nebulizers that recorded the date and time of each treatment over a period of 4 weeks. Poor compliance was defined as taking <70% of the prescribed dose (or <60% for those prescribed treatments five or more times daily). SETTING: Patients were seen at the hospital COPD outpatient clinic. The compliance data obtained were recorded while they were at home. PATIENTS: Ninety-three patients aged 44 to 76 years (mean, 64.9 years) were recruited from the hospital nebulizer database. MEASUREMENTS: Patients completed a self-reported quality of life scale, the St. George's Respiratory Questionnaire (SGRQ), both before (SGRQ1) and after (SGRQ2) the 4-week study period to look at whether quality of life was either predictive of or subsequent to level of compliance. RESULTS: Data were obtained from 82 patients. Mean compliance was 57% (range, 0 to 124%). Thirty-six (44%) patients were compliant and 46 (56%) were poorly compliant. There was no difference between the two groups in age or sex distribution. Compliance was negatively correlated with the total score on the SGRQ2 (p=0.03). CONCLUSION: The study shows that levels of compliance with nebulized therapy are low in a large proportion of patients with COPD and that patients with low levels of compliance report greater impairment in their quality of life.

Corticosteroids restore the balance between locally produced Th1 and Th2 cytokines and immunoglobulin isotypes to normal in sarcoid lung.

In this study, we have investigated the balance between Th1- and Th2-like activity in the lungs in sarcoidosis and have determined the effect of corticosteroid treatment on this. Twenty-one patients with acute untreated sarcoidosis were investigated by bronchoalveolar lavage (BAL) and compared with 11 normal volunteers. Sixteen of the sarcoid patients required corticosteroid therapy and seven of these were reinvestigated after 2-3 months' treatment. In order to assess Th1- and Th2-like activity in the lungs, IgG subclasses and IgE were measured in BAL fluid and serum, and IL-2, IL-4 and interferon-gamma (IFN-gamma) in BAL. In patients with untreated sarcoidosis, albumin-corrected BAL/serum ratios for IgG4 and IgE were significantly reduced (IgG4, 1.04 +/- 0.18 (mean +/- s.e.m.); IgE 9.58 +/- 3.11) compared with those in normal controls (IgG4 5.3 +/- 0.72, P < 0.001; IgE 67.7 +/- 28.9, P < 0.01). Estimates of actual levels of immunoglobulins produced in the lungs were also made and showed extremely high levels of total IgG in sarcoid patients (39.56 +/- 8.2 mg/l) compared with controls (1.17 +/- 0.5 mg/l, P < 0.001). Although there was no difference between the groups in amount of IgG4 locally produced, the proportion of total IgG which was IgG4 was greatly reduced in those with sarcoidosis (1.6 +/- 0.4% compared with 38.5 +/- 3.2%; P < 0.001). Lavage levels of IL-4 were also reduced in sarcoid patients (IL-4 2.103 +/- 0.21 pg/ml) compared with those in normals (IL-4 6.8 +/- 1.05; P < 0.001). Levels of IL-2 were lower (7.63 +/- 0.51 pg/ml compared with 9.4 +/- 0.95 pg/ml), but this difference was not significant. IFN-gamma, however, could not be detected above 0.4 pg/ml in any of the normal lavage fluid, but was detectable in 12/21 patients with sarcoidosis (chi2 = 7.74; P < 0.001). These changes reverted towards normal on treatment with oral corticosteroids. The mean albumin-corrected BAL/serum ratio for IgG4 before treatment was 0.88 +/- 0.33 compared with 5.5 +/- 2.1 (P < 0.05) on treatment, and for IgE before treatment 9.52 +/- 2.15 compared with 50.8 +/- 17.9 (P < 0.05) on treatment. Total IgG produced in the lung fell from 26.16 +/- 7.9 to 6.12 +/- 2.4 mg/l (P < 0.001) on treatment, and the proportion of IgG4 locally produced rose from 2.3 + 0.8% to 23.9 +/- 6.1% (P < 0.01). The mean level of IL-4 in lavage before treatment was 2.53 +/- 0.34 pg/ml compared with 4.7 +/- 0.34 (P < 0.001) on treatment. Levels of IL-2 also rose significantly on treatment from 8.74 +/- 0.95 pg/ml before to 14.44 +/- 1.38 pg/ml (P < 0.001) on treatment. Levels of IFN-gamma fell from 1.65 +/- 0.43 pg/ml before treatment to undetectable levels in all patients (P < 0.001) on treatment. These results demonstrate an imbalance between Th1- and Th2-like activity in the lungs in sarcoidosis, with suppression of Th2 and increase in Th1. Corticosteroid therapy restores the normal balance between Th1 and Th2 cytokines and immunoglobulins in the lungs, suggesting an effect on local immune regulation.

Psychological factors associated with use of home nebulized therapy for COPD.

This study examined the relationship between adherence to domiciliary nebulized therapy and psychological factors; patient attitudes, anxiety, depression, and quality of life. Ninety three patients aged 45-77 yrs with chronic obstructive pulmonary disease (COPD) and using domiciliary nebulizers were recruited from a hospital database. They completed the St George's respiratory questionnaire (SGRQ)-1 and the hospital anxiety and depression scale (HADS) and attended a semistructured interview. Their usual nebulizers were replaced by Dataloggers, which record the date, time and duration of each treatment, to use for 4 weeks. The SGRQ was then repeated (SGRQ-2). Eighty two patients completed the study. Fifty six percent were poorly adherent; taking less than 70% of the dose prescribed (or less than 60% on regimens of > or = 5 times daily). The total scores on the SGRQ-2 were negatively correlated with percentage adherence. Multiple regression analysis showed that the SGRQ-2 total score was associated with percentage adherence, depression score, feeling supported by clinic staff, and patients feeling that they tried to ignore their chest disease. Patients who report poor quality of life are more likely to be depressed, feel unsupported by clinic staff and be poorly adherent to treatment. Increased levels of clinic support, with the addition of psychological treatments, may be of benefit to some patients with chronic obstructive pulmonary disease.