bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of 2 major loci linked to autoimmune hemolytic anemia in NZB mice
Authors: Kikuchi Shuichi , Amano Hirofumi , Amano Eri , Fossati-Jimack Liliane , Santiago-Raber Marie-Laure , Moll Thomas , Ida Akinori , Kotzin Brian L. , Izui Shozo
Published: April 2005

Using a cohort of C57BL/6 (B6) × (NZB × B6)F1 backcross male mice bearing the Yaa (Y-linked autoimmune acceleration) mutation, we mapped and characterized the NZB-derived susceptibility loci predisposing to the development of autoimmune hemolytic anemia (AHA). Our analysis identified 2 major loci on NZB chromosome 7 and chromosome 1 linked with Coombs antierythrocyte autoantibody production, and their contributions were confirmed by the analysis of B6.Yaa mice (B6 mice bearing the Yaa mutation) congenic for each NZB-derived susceptibility interval. A newly identified Aia3 (autoimmune anemia 3) locus present on NZB chromosome 7 selectively regulated Coombs antibody responses, while the second locus, directly overlapping with Nba2 (NZB autoimmunity 2) on chromosome 1, promoted the development of AHA, likely as part of its effect on overall production of lupus autoantibodies. A higher incidence of Coombs antibody production in B6.Aia3 congenic mice (B6 mice bearing the NZB-Aia3 locus) than B6.Nba2 mice (B6 mice bearing the NZB-Nba2 locus) indicated a major role for Aia3 in AHA. Notably, lack of expansion of B1 cells in B6.Aia3 congenic mice argued against the involvement of this subset in AHA. Finally, our analysis of BC mice also demonstrated the presence of a B6-derived H2-linked locus on chromosome 17 that apparently regulated the production of Coombs antibodies as a result of its overall autoimmune promoting effect.
Exhaled NO may predict the decline in lung function in bronchiolitis obliterans syndrome
Authors: Brugière O. , Thabut G. , Mal H. , Marceau A. , Dauriat G. , Marrash-Chahla R. , Castier Y. , Lesèche G. , Colombat M. , Fournier M.
Published: April 2005

Bronchiolitis obliterans syndrome (BOS) remains the leading cause of morbidity/mortality following lung transplantation. In recipients with BOS, markers predicting the decline in lung function are needed. The aim of this longitudinal study was to determine whether exhaled nitric oxide fraction (FeNO) measurements provide useful information for discriminating patients with unstable BOS from those with stable BOS.

During a 14-month period, 145FeNOmeasurements were performed in 50 lung transplant recipients. Among them, 16 recipients with BOS (32FeNOmeasurements) were analysed. For eachFeNOmeasurement, the patients were classified into three groups according to the decline in forced expiratory volume in one second (FEV1) within the following 6 months: 1) stable BOS free; 2) stable BOS (decline in FEV1of <5%); and 3) unstable BOS (decline in FEV1of ≥15%).

The meanFeNOin patients with unstable BOS was significantly increased compared with that in stable BOS-free patients (18.4±5.7versus9.7±3.7 ppb) and that in patients with stable BOS (18.4±5.7versus9.7±3.3 ppb).

The present findings suggest that, in patients with bronchiolitis obliterans syndrome, a raised exhaled nitric oxide fraction may predict the development of worrisome functional impairment during long-term follow-up.
LPS-induced lung inflammation is linked to increased epithelial permeability: role of MLCK
Authors: Eutamene H. , Theodorou V. , Schmidlin F. , Tondereau V. , Garcia-Villar R. , Salvador-Cartier C. , Chovet M. , Bertrand C. , Bueno L.
Published: April 2005

The respiratory system is directly exposed to low levels of lipopolysaccharide (LPS), present as a contaminant on airborne particles. In cystic fibrosis, the prevailing data identify structural changes of the airway epithelium, as well as tight junction dilatation. This study was aimed at determining the contribution of myosin light chain kinase to maintaining airway epithelium barrier integrity in the lung inflammatory response to LPS in rats.

The effects of the selective myosin light chain kinase inhibitor, 5-iodonaphthalene-1-sulphonyl-homopiperazine (ML-7), were evaluated: 1) on pulmonary inflammation and airway epithelium barrier permeability alterations induced by intra-tracheal LPS fromPseudomonas aeruginosa; and 2) on levels of the phosphorylated form of the myosin light chain, which is increased in a human airway epithelial cell line (NCI-H292) and tracheal tissue after LPS exposure.

The results show that LPS increased airway epithelium barrier paracellular permeability and lung inflammation, and that pre-treatment with ML-7 inhibited both effects. This effect of ML-7 was associated with the inhibition of phosphorylated myosin light chain in both NCI-H292 cells and tracheal tissue.

The data, obtained usingin vivoandin vitroapproaches, demonstrate a key role for myosin light chain kinase in lung inflammation, and suggest that myosin light chain kinase could be a potential target for novel drugs intended for relief of lung injury.
The inositol trisphosphate pathway mediates platelet-activating-factor-induced pulmonary oedema
Authors: Göggel R. , Uhlig S.
Published: April 2005

Platelet-activating factor (PAF) is a pro-inflammatory lipid mediator that increases vascular permeability by simultaneous activation of two pathways, one dependent on the cyclooxygenase metabolite prostaglandin E2and the other on the sphingomyelinase metabolite ceramide. The hypothesis that part of the PAF-induced oedema is mediatedviathe inositol 1,4,5-trisphosphate (IP3) pathway or Rho kinase pathway was investigated.

Oedema formation was induced in isolated perfused rat lungs by injection of 5 nmol PAF into the pulmonary artery. Lungs were pre-treated with specific inhibitors: edelfosine (L108) to block phosphatidyl-inositol-specific phospholipase C, xestospongin to block the IP3receptor, 5-iodonaphthalene-1-sulphonyl-homopiperazine (ML-7) to block myosin light chain kinase, and (+)-R-trans-4-(aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y27632) to block Rho-associated protein kinase.

Pre-treatment with L108 or xestospongin reduced PAF-induced oedema formation by 58 and 56%, respectively. The effect of L108 was additive to that of the cyclooxygenase inhibitor acetyl salicylic acid (88% oedema reduction). PAF-induced oedema formation was also reduced if extracellular calcium concentrations were lowered. Furthermore, treatment with ML-7 reduced oedema formation by 54%, whereas Y27632 was without effect.

It is concluded that platelet-activating-factor-triggered oedema is mediated by activation of the inositol 1,4,5-trisphosphate pathway, influx of extracellular calcium and subsequent activation of a myosin light chain kinase-dependent and Rho-associated-protein-kinase-independent mechanism.
Increased expression of p38 MAPK in human bronchial epithelium after lipopolysaccharide exposure
Authors: Roos-Engstrand E. , Wallin A. , Bucht A. , Pourazar J. , Sandström T. , Blomberg A.
Published: April 2005

Bacterial endotoxin (lipopolysaccharides (LPS)) is normally present in the wall of Gram-negative bacteria and has potent pro-inflammatory properties. Exposure to LPS has been shown to induce neutrophilic airway inflammation in humans. The aim of this investigation was to study the early inflammatory responses to LPS exposure in human airway mucosain vivo.

In total, 15 healthy nonsmoking volunteers participated. Bronchoscopy was performed on two separate occasions, 3 h after saline inhalation and after inhalation of 50 μg LPS in saline. Endobronchial mucosal biopsy specimens were taken and stained immunohistochemically using a panel of monoclonal antibodies directed against mitogen-activated protein kinases (MAPKs), transcription factors, cytokines, adhesion molecules and inflammatory cells.

Expression of p38 MAPK increased as a consequence of LPS exposure, as determined by both total epithelial staining and nuclear location. These two responses were strongly associated. Epithelial expression of interleukin-8 showed a tendency towards a significant increase after LPS compared to saline. Epithelial mast cell numbers were increased after LPS, whereas neutrophil numbers were unchanged.

Inhalation of lipopolysaccharide induced activation of the bronchial epithelium, as demonstrated 3 h after exposure by increased expression of p38 mitogen-activated protein kinase and interleukin-8, and may represent early regulatory steps in the subsequent development of a neutrophilic bronchial inflammation.
Significance of positiveStenotrophomonas maltophiliaculture in acute respiratory tract infection
Authors: Pathmanathan A. , Waterer G. W.
Published: April 2005

Stenotrophomonas maltophiliais a common coloniser of the respiratory tract of patients with chronic lung disease, and, in the absence of pneumonia or bacteraemia, is often ignored by physicians at the Royal Perth Hospital (Perth, Australia). Experience at the Royal Perth Hospital was reviewed to determine whether ignoringS. maltophiliain this setting has any apparent effect on clinical outcome.

All patients who presented with an acute respiratory illness and yielded a positive culture forS. maltophiliabetween 1995 and 2002 were retrospectively reviewed. All subjects had to yield a positive respiratory isolate ofS. maltophiliaand undergo chest radiography within 24 h of the isolate being obtained.

Ninety-two episodes were identified in 89 individuals; 64 showed no evidence of consolidation. Of the study group, 51 (80.0%) received no anti-S. maltophiliaantibiotic therapy and 21 (32.8%) had a nosocomially acquired isolate. The overall mortality rate was 20.3%. There was no impact of anti-S. maltophiliatherapy on outcome. The only independent predictor of mortality was serum albumin level.

As there was no measurable impact of antibiotic therapy, in the absence of consolidation, a positive respiratory tract isolate ofStenotrophomonas maltophiliaprobably represents colonisation of a severely impaired host rather than invasive disease.
Standardised mortality rates in females and males with COPD and asthma
Authors: Ringbaek T. , Seersholm N. , Viskum K.
Published: April 2005

Mortality studies of males and females with chronic obstructive pulmonary disease (COPD) and asthma have suggested that females have a poorer prognosis than males, but the results are either not unanimous or based on poorly characterised patients. The current study analysed the mortality of 279 asthma patients and 869 COPD patients, who were seeking pension due to disability, and compared mortality rates with expected rates derived from the general population.

The mean follow-up period was 13.3 yrs (range 2.5–22.4 yrs) during which time 96 (34.4%) and 671 (77.2%) deaths were identified among asthma and COPD patients, respectively. The average age at study entry was 46.8 and 56.6 yrs, and the average forced expiratory volume in one second (FEV1) was 68.8 and 44.1 % predicted in the two diagnostic groups. After adjustment for predictors of survival (age, FEV1% predicted, chronic bronchitis, body mass index, smoking status, oral prednisolone, ischaemic heart disease, and cor pulmonale), the relative risk of death was 1.21 (95% confidence interval: 0.77–1.89) and 0.98 (0.83–1.16) in females compared with males, in asthma and COPD patients, respectively.

The standardised mortality rate (SMR) for males was 1.54 (1.10–2.09) and 2.7 (2.5–3.0), and for females 1.91 (1.44–2.49) and 4.8 (4.2–5.4), in asthma and COPD patients, respectively. Direct comparison of the SMR of males and females showed that females had higher mortality than males, with a rate ratio of 1.24 (0.82–1.84) and 1.8 (1.5–2.0), in asthma and COPD patients, respectively. Poisson regression analysis with control for the confounders did not change this result.

Females and males with the same level of obstructive lung disease appear to have the same level of mortality. However, using standardised mortality rates, females have a higher mortality than males, suggesting that the protective effect of being female is lost in chronic obstructive pulmonary disease patients.
Effects of salbutamol and enantiomers on allergen-induced asthmatic reactions and airway hyperreactivity
Authors: Westerhof F. J. , Zuidhof A. B. , Kok L. , Meurs H. , Zaagsma J.
Published: April 2005

Salbutamol consists of a racemic mixture ofR- andS-salbutamol.R-salbutamol (levalbuterol) is the active bronchodilating enantiomer, whereasS-salbutamol is thought to be pharmacologically inactive or to exert adverse effects.

This study evaluated the bronchoprotective effects of inhalation of therapeutically relevant doses of the racemate and individual enantiomers in guinea pigs.

It was found that basal airway reactivity to histamine was similarly reduced 30 min after inhalation of equivalent doses ofRS- andR-salbutamol; this protective effect disappeared within 3 h. Inhalation ofRS- andR-salbutamol 30 min before and 5.5 h after allergen challenge suppressed allergen-induced airway hyperreactivity to histamine after the early and late asthmatic reaction, completely inhibiting the early asthmatic reaction and tending to reduce the development of the late asthmatic reaction. At 5 h after allergen challenge, the inhibition of airway hyperreactivity was more pronounced in animals treated withR-salbutamol compared to racemate-treated animals. Both basal airway reactivity and allergen–induced hyperreactivity were not affected byS-salbutamol. Inflammatory cell infiltration was not affected by the racemate or the individual enantiomers.

In conclusion, inhalation of therapeutically relevant doses ofR- andRS-salbutamol effectively suppress allergen-induced airway reactivity after the early and late asthmatic reactions, theR-enantiomer being slightly more potent with respect to early airway reactivity than the racemate. No adverse effects were observed for theS-enantiomer.
The effects of body weight on airway calibre
Authors: King G. G. , Brown N. J. , Diba C. , Thorpe C. W. , Muñoz P. , Marks G. B. , Toelle B. , Ng K. , Berend N. , Salome C. M.
Published: April 2005

Increased wheeze and asthma diagnosis in obesity may be due to reduced lung volume with subsequent airway narrowing.

Asthma (wheeze and airway hyperresponsiveness), functional residual capacity (FRC) and airway conductance (Gaw) were measured in 276 randomly selected subjects aged 28–30 yrs. Data were initially adjusted for smoking and asthma before examining relationships between weight and FRC (after adjustment for height), and between body mass index (BMI = weight·height−2) andGaw(after adjustment for FRC) by multiple linear regression, separately for females and males.

For males and females, BMI (±95% confidence interval) was 27.0±4.6 kg·m−2and 25.6±6.0 kg·m−2respectively,Gawwas 0.64±0.04 L·s−1·cmH2O−1and 0.57±0.03 L·s−1·cmH2O−1, and FRC was 85.3±3.4 and 84.0±2.9% of predicted. Weight correlated independently with FRC in males and females. BMI correlated independently and inversely withGawin males, but only weakly in females.

In conclusion, obesity is associated with reduced lung volume, which is linked with airway narrowing. However, in males, airway narrowing is greater than that due to reduced lung volume alone. The mechanisms causing airway narrowing and sex differences in obesity are unknown.
Human immune recognition-based multicomponent subunit vaccines against tuberculosis
Authors: Sable S. B. , Verma I. , Behera D. , Khuller G. K.
Published: April 2005

The cell-mediated immune response, with its shift in favour of type-1 over type-2 T-helper cell immune response, is generally regarded as essential to protection against mycobacterial infections. The aim of this study was to evaluate the protective potential of two multicomponent subunit vaccines (MSV-1 and MSV-2) against tuberculosis (TB) based on human immune recognition.

MSV-1 consisted of five immunodominant antigens (TB10.4, early secretory antigenic target (ESAT)-6, culture filtrate protein (CFP)-8, CFP-10 and CFP-15) selected from a group of polypeptides, which induced a predominant T-cell response in immune human subjects, whereas MSV-2 consisted of antigens (CFP-11, CFP-21, CFP-22.5,Mycobacterium tuberculosisprotein (MPT)-64 and CFP-31) selected from a group of polypeptides which induced a subdominant T-cell response along with the antibody response.

Both of these sets of polypeptides were extensively recognised in healthy individuals with significant interferon gamma release compared to the diseased population. In C57BL/6J mice, at the level of the lungs, the order of protective efficacy for the test vaccines was: bacille Calmette–Guérin (BCG)>MSV-2>MSV-1. The protective efficacy of MSV-1 was found to be significantly less than that of MSV-2 and BCG at the level of spleen, whereas that of MSV-2 was comparable to that of BCG.

The results of this study indicate that high T-helper cell type 1 response-inducing polypeptides selected on the basis of human immune recognition do not necessarily impart protection during vaccination experiments.
Cheyne-Stokes respiration and supine dependency
Authors: Sahlin C. , Svanborg E. , Stenlund H. , Franklin K. A.
Published: April 2005

The influence of position during sleep on central apnoeas during Cheyne-Stokes respiration has not previously been studied systematically. The current authors aimed to study the effect of body position and sleep stages on central sleep apnoeas during Cheyne-Stokes respiration.

A total of 20 consecutive patients with cardiovascular diseases and central sleep apnoea during Cheyne-Stokes respiration were investigated using nocturnal polysomnography, including a body position sensor mounted on the patient's sternum.

The mean central apnoea–hypopnoea index was significantly higher in the supine position than in nonsupine positions (41±13versus26±12). The central apnoea–hypopnoea index was highest in sleep stages 1 and 2, and lowest in slow-wave sleep and rapid eye movement sleep. In every sleep stage, central apnoeas and hypopnoeas were more prevalent in the supine position compared with nonsupine positions.

In conclusion, sleep in the supine body position increases the frequency of apnoeas and hypopnoeas in patients with Cheyne-Stokes respiration.
Genetics of fibrosing lung diseases
Authors: Grutters J. C. , du Bois R. M.
Published: April 2005

Genetic studies in familial lung fibrosis have demonstrated an association with surfactant protein C genes: two mutations have been found resulting in protein misfolding and causing type-II epithelial cell injury. Remarkably, different histological patterns were observed in the affected subjects, suggesting the influence of modifier genes and/or environmental factors. Surfactant protein C gene variations have not, however, been associated with sporadic cases,i.e.idiopathic pulmonary fibrosis (IPF).

Susceptibility to IPF probably involves a combination of polymorphisms related to epithelial cell injury and abnormal wound healing. To date, the genetic associations with IPF that have been reported in different cohorts include the genes encoding tumour necrosis factor (TNF; −308 adenine), interleukin-1 receptor antagonist (+2018 thymidine) and association with severity and progression (interleukin-6/TNF receptor II and transforming growth factor-β1 (TGFB1; +869 cytosine)), but none of these associations have been replicated by others.

Unlike in IPF, immunological inflammation seems to be more prominent in the pathogenesis of scleroderma lung fibrosis, being an autoimmune disease with specific autoantibodies, such as antitopoisomerase antibodies, in patients with diffuse lung disease, and anticentromere antibodies, in patients with pulmonary vascular disease. Antitopoisomerase antibody positivity is associated with the carriage of human leukocyte antigen DRB1*11 and DPB1*1301 alleles, suggesting the recognition of a specific amino-acid motif. Extended haplotype analysis also supports the conclusion that TNF may be the primary association with anticentromere positivity. Intriguingly, associations with TGFB1 and genes involved in extracellular matrix homeostasis have been reported in this disease.

In conclusion, significant steps forward have been taken in the understanding of the genetic contribution to fibrosing lung diseases, but major challenges lay ahead. It is the present authors' opinion that only a combined approach studying large numbers of familial and sporadic cases, all clinically well phenotyped, using multiple distinct cohorts, and genotyped according to relevant gene ontologies will be successful. It will be necessary to be particularly vigilant with regard to phenotype; the absence of very strong reproducible associations may be because of the rigidity of phenotype definition, coupled with the possibility that idiopathic pulmonary fibrosis may still be a heterogeneous group of diseases, despite the more rigid definition set out by the European Respiratory Society/American Thoracic Society statement.
A novel duplication polymorphism in the FANCApromoter and its association with breast and ovarian cancer
Authors: Thompson Ella , Dragovic Rebecca L , Stephenson Sally-Anne , Eccles Diana M , Campbell Ian G , Dobrovic Alexander
Published: April 2005

The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region.

Methods

We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer.

Results

The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours.

Conclusion

The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.
Effects of multiple sclerosis on respiratory functions
Authors: Mutluay F K , Gürses H N , Saip S
Published: April 2005

Objectives: To measure respiratory functions of ambulatory patients with multiple sclerosis and compare the results with expected values from healthy general population data. Further, to study the correlation of respiratory function impairment with the multiple sclerosis-induced disability level.

Subjects: Thirty-eight patients with definite diagnosis of multiple sclerosis from the multiple sclerosis outpatient clinic.

Methods: The Expanded Disability Status Scale (EDSS) scores (mean 4.34±1.39) were evaluated to measure disability level. Respiratory functions tested in the laboratory included spirometric (FVC, FEV1, FEV1/FVC), maximal inspiratory (MIP) and expiratory (MEP) mouth pressure measurements. Patients were clinically assessed using a pulmonary dysfunction index (PDI) and dyspnoea index; various breathing features were also recorded.

Results: With respect to expected values from healthy general population, important decreases were found in mouth pressures with MIP (77%±23%, p ≃ 0) and MEP (60%±13%, p ≃ 0) while spirometric measures were significantly but less affected (FVC 94%±12%, p < 0.01, FEV1 91%±16%, p < 0.001). FEV1/FVC ratios were normal. Notable increases in PDI (5.58±0.68, p ≃ 0) and dyspnoea index (0.32±0.47, p ≃ 0) were observed. Significant relationships (p < 0.01) between respiratory function impairment and the multiple sclerosis disability level could be detected for FVC, MEP and PDI.

Conclusions: Multiple sclerosis clearly impairs respiratory functions; maximal mouth pressures are more severely reduced. This impairment increases with multiple sclerosis-induced disability level but is found to be independent from duration of disease.
The measurement properties and performance characteristics among older people of TURN180, a test of dynamic postural stability
Authors: Fitzpatrick C , Simpson J M , Valentine J D , Ryder S , Peacock-Edwards T , Sidnell P , Colognese M
Published: April 2005

Objectives: To establish the measurement properties of TURN180, a test of dynamic postural stability.

Design: One physiotherapist conducted three trials of TURN180, one of which was also observed by a second therapist.

Setting: A day unit for elderly people accepting both inpatients and outpatients.

Subjects: Sixty-six people (mean age 82.45 years), only six (9.1%) of whom could walk without using a walking aid.

Main measurement: The number of steps that a person takes to step around 180 degrees. A step is defined as any attempt on the subject's part to take a step, successful or not.

Results: Repeatability is good, intraclass correlation coefficient = 0.828; the minimal detectable change revealed that in order to be considered a real improvement the number of steps the person takes to complete the postintervention TURN180 must be 28–29% fewer than the preintervention count. As long as the protocol is followed carefully, between-observer agreement is good, with differences between two observers rarely exceeding one step. People who had fallen in the previous year took statistically significantly more steps than those who had not done so to complete TURN180. Requesting written as well as oral consent seems to reduce the likelihood of an elderly patient agreeing to participate in a study.

Conclusion: TURN180 yields repeatable (retest reliable) and valid data about a person's dynamic postural stability, especially the minimal detectable change which allows clinicians to judge whether any change in their patient's performance is real.
Effectiveness of the Easy-Up Handle in acute rehabilitation
Authors: Eriksrud Ola , Bohannon Richard W
Published: April 2005

Objective: The ability to attain standing without assistance is important to independent functioning. The objectives of this study, therefore, were to: (1) determine the effectiveness of the Easy-Up Handle for enabling otherwise dependent patients to attain standing from an armless chair and (2) establish whether knee extension force played a role in such effectiveness.

Design: Cross-sectional descriptive study and explicatory experiment.

Setting: Acute rehabilitation unit.

Subjects: A subset ( n = 26) of 107 primarily elderly patients described in a previous study. The subjects were selected because of their inability to stand from an armless chair, even when using their upper limbs.

Main measures: The ability to stand from the same chair when using an Easy-Up Handle. Hand-held dynamometer measures of the combined strength of the lower extremities.

Results: Eight of 26 otherwise dependent patients were able to stand up independently with the Easy-Up Handle. Whether or not they were able to attain standing with the Easy-Up Handle was predicted by their combined knee extension force and by their combined force normalized against body weight. The Pearson correlations between stand-up independence (yes, no) and the forces were 0.496 and 0.543, respectively.

Conclusions: The Easy-Up Handle can facilitate independence in chair rise for some patients otherwise unable to stand from sitting. Even with the Easy-Up Handle, however, a threshold of knee extension force is required.
Falls and injury prevention should be part of every stroke rehabilitation plan
Authors: Mackintosh S FH , Hill K , Dodd K J , Goldie P , Culham E
Published: April 2005

Objective: To evaluate falls incidence, circumstances and consequences in people who return home after stroke rehabilitation, so that appropriate falls and injury prevention strategies can be developed.

Design: Prospective cohort study.

Setting: Community.

Subjects: Fifty-six subjects with stroke who were participating in a rehabilitation programme and returning to live in a community setting completed the study.

Main measures: Subjects completed a prospective falls diary for six months after discharge from rehabilitation, and were interviewed after falls. Physical function was measured by the Berg Balance Scale (BBS) and the Functional Independence Measure (FIM).

Results: Forty-six per cent of people (26/56) fell, with most falls (63/103 falls) occurring in the two months after discharge from rehabilitation. One subject had 37 similar falls and these falls were excluded from further analysis. Falls occurred more often indoors (50/66), during the day (46/66) and towards the paretic side (25/66). People required assistance to get up after 25 falls (38%) and 36 falls (55%) resulted in an injury. People sought professional health care after only 16 falls, and activity was restricted after 29 falls (44%). The Berg Balance Scale and Functional Independence Measure scores were lower in people who had longer lies after a fall, and who restricted their activity after a fall (p < 0.05). Lower physical function scores were also associated with falling in the morning, wearing multifocal glasses at the time of a fall, and injurious falls (p < 0.05).

Conclusion: Falls are common when people return home after stroke. Of concern are the small number seeking health professionals’ assistance after a fall, the high proportion restricting their activity as a result of a fall and the number of falls occurring towards the paretic side.
A comparative evaluation of oxygen consumption and gait pattern in amputees using Intelligent Prostheses and conventionally damped knee swing-phase control
Authors: Datta Dipak , Heller Ben , Howitt John
Published: April 2005

Objective: To compare the gait of amputees wearing conventionally damped pneumatic swing-phase control knees and microchip-controlled Intelligent Prostheses.

Design: Crossover trial.

Setting: An amputee rehabilitation centre in a teaching hospital.

Participants: Ten established unilateral transfemoral prosthetic users were asked to participate in the trial; all agreed.

Interventions: The amputees were assessed wearing pneumatic swing-phase control knees and then with the Intelligent Prosthesis.

Main outcome measures: Oxygen consumption while walking at different speeds on a treadmill, video-recording of gait assessed by a panel and temporal–spatial parameters of gait whilst walking at slow, fast or normal speeds in a gait laboratory.

Results: Mean oxygen cost for all subjects at 0.69 m/s was 0.33 ml/kg.m with the conventional limb and 0.30 ml/kg.m with the Intelligent Prosthesis ( p–0.01). At 1.25 m/s the mean oxygen cost for the conventional limb was 0.24 ml/kg.m and for the Intelligent Prosthesis was 0.22 ml/kg.m (not significant). The ANOVA analysis showed that oxygen cost was similar at normal walking speeds but increased more at lower speeds for the pneumatic swing-phase control leg compared to the Intelligent Prosthesis ( p<0.02). There were no significant differences in subjective gait evaluation or temporal and spatial gait parameters.

Conclusion: At lower speeds oxygen cost was lower with the Intelligent Prosthesis. Gait analysis detected no significant changes between the two legs.
The co-ordination of bimanual rapid aiming movements following stroke
Authors: Rose D K , Winstein C J
Published: April 2005

Objective: To determine the role of anticipatory and movement control processes for the coordination of bimanual target aiming in individuals post stroke.

Subjects: Thirty adults with chronic stroke and 30 individuals without stroke history.

Design: A two-group (stroke, control) by two-aiming type (unimanual, bimanual) by two-limb (paretic, nonparetic; left, right for controls) design with repeated measures on the last two factors.

Outcome measures: Kinematic analyses of performance and psychometric measures of reaction time, movement time, peak resultant velocity, time to and after peak resultant velocity and interlimb timing for movement initiation and target impact.

Results: Compared with unimanual aiming, the nonparetic limb exhibited a prolonged movement time in the bimanual condition; the locus for prolongation was primarily in the deceleration phase. This adaptive response allowed for a nearly simultaneous (both limbs) target impact in 81% of trials. Compared with the unimanual condition, the nonparetic limb exhibited a lower peak velocity (10%) in the bimanual condition. Conversely, compared with the unimanual condition, the paretic limb exhibited a higher peak velocity (4%) in the bimanual condition. This disociation between limb and condition was observed for the stroke group but not the control group.

Conclusions: The interlimb coordination that emerged for the stroke group revealed a complex and asymmetric contribution from each limb mediated through anticipatory and motor control processes. We suggest that this coordination may be harnessed for future bimanual intervention approaches to rehabilitation of upper limb function after stroke.
Reliability and validity of the Northwick Park Dependency Score (NPDS) Swedish version 6.0
Authors: Svensson Siv , Sonn Ulla , Sunnerhagen Katharina Stibrant
Published: April 2005

Objective: To translate, to test inter-rater and intra-rater reliability and concurrent validity of the Basic Care Needs (BCN) section of the Northwick Park Dependency Score (NPDS).

Design: Test–retest reliability and validity testing. Observed data were collected by the staff (nursing staff, occupational therapists).

Setting: Three rehabilitation units.

Subjects: Forty inpatients between 16 and 65 years of age with brain injury were included.

Main measures: Inter-rater and intra-rater reliability was calculated by percentage agreement (PA) and unweighted kappa measure. Concurrent validity was examined by computing Goodman–Kruskal's gamma, a nonparametric statistic for degree of association between the BCN score and the total score of the Functional Independence Measure (FIM).

Results: Inter-rater reliability showed a good percentage agreement between nursing staff. Between nursing staff and occupational therapists the percentage agreement was lower especially in one item. Intra-rater reliability showed a good percentage agreement for all assessors. Concordance was good with a gamma 0.83 and an asymptotic error (ase) of 0.04, for nursing staff and for occupational therapists — 0.87, ase 0.04.

Conclusion: The BCN section of NPDS was found to be inter-rater and intra-rater reliable, to have concurrent validity. Further studies are needed on clinical utility. The instrument can be used for assessment of dependency for individual patients with brain injury, and information when transferring between different caregivers. Further studies need to investigate the sensitivity of the instrument.
‘But is the difference clinically significant?’
Authors: Wade Derick
Published: April 2005

The statement that a difference or change found in a research study is statistically significant is frequently met with the response, ‘but is it clinically significant?’. This question seems entirely reasonable and uncontentious until one asks how to determine or define clinical significance. Significance must always have an object; significant to whom? Furthermore it needs elaboration; significant in what way? Once these questions are raised, it becomes apparent that the slick, apparently sensible question is in fact extremely difficult to answer and may have multiple answers: the patient may value being free of discomfort, but the payer may only value achieving less cost in long-term care and the clinician may wish to see change in activities. The use of this question by funding organizations may disadvantage rehabilitation. This Editorial explores the substance of this question, concluding that the question can only be answered by the individual patient concerned, and that research studies should perhaps explore more fully what is actually of significance to patients.
Patients’ Privacy of the Person and Human Rights
Authors: Woogara Jay
Published: April 2005

The UK Government published various circulars to indicate the importance of respecting the privacy and dignity of NHS patients following the implementation of the Human Rights Act, 1998. This research used an ethnographic method to determine the extent to which health professionals had in fact upheld the philosophy of these documents. Fieldwork using nonparticipant observation, and unstructured and semistructured interviews with patients and staff, took place over six months in three acute care wards in a large district NHS trust hospital. Applying the principles of phenomenology and grounded theory, the data were analysed and the contents organized into 11 key categories, leading to the formulation of a privacy model. The level of intrusion into patients’ privacy by health professionals was measured against the benchmarking of the ‘dignity and privacy’ factors contained in the Department of Health’s The essence of care document and Article 8(2) of the Human Rights Act. The findings established that patients had little privacy in the wards, and that the terms ‘privacy of the person’ and ‘dignity’ are interrelated.
Diversity training for psychiatrists
Authors: Dogra Nisha , Karim Khalid
Published: April 2005

There is great concern about the access of ethnic minority clients to appropriate healthcare and the treatment they experience once they gain access to services. There have been recent calls for training in cultural diversity to be prioritised for mental healthcare professionals, including psychiatrists. In this article we discuss the term ‘cultural diversity’ and consider its relevance to psychiatrists. We then briefly review some of the training currently available, discussing related issues and problems, including the lack of evaluation. We suggest how psychiatrists may need to change their approach to this subject.
Encouraging user involvement in mental health services
Authors: Tait Lynda , Lester Helen
Published: April 2005

This article summarises the current research evidence base on user involvement in mental health services from both policy and practical perspectives. We begin by examining the many meanings of the term ‘mental health service user’ and the policy imperatives for user involvement, to provide a context for later examples of good practice. We then discuss what is meant by ‘involvement’ and the reasons why user involvement is particularly important in mental health services. Finally, we describe some of the traditional barriers to involvement and a number of examples of positive practice across a range of different aspects of mental health service development and delivery.
Preventing dementia
Authors: Purandare Nitin , Ballard Clive , Burns Alistair
Published: April 2005

Epidemiological evidence has identified key strategies that may be used in the prevention of both Alzheimer's disease and vascular dementia. These strategies may be loosely divided into three areas: treatment of vascular risk factors, neuroprotection and increasing neuronal reserves. Evidence from randomised controlled trials already exists for treatment of hypertension but results for statins have been disappointing. Most of the intervention trials currently in progress focus on one or two risk factors and include cognition or dementia only as a secondary outcome. The potential of intervention strategies awaits confirmation by randomised controlled trials that target multiple risk factors in at-risk people with mild cognitive impairment, with incident dementia as the primary outcome.
Neuroimaging in schizophrenia: what does it tell the clinician?
Authors: Woolley James , McGuire Philip
Published: April 2005

Neuroimaging has been used in clinical practice for over 30 years, but it is still perceived as rarely offering the psychiatrist much help in direct patient management. As newer imaging modalities are introduced (from computed tomography and positron and single photon emission tomography to magnetic and functional magnetic resonance imaging), the promise of imminent clinical utility is reawakened, only to fade as the innovation is shown to be another, albeit useful, research tool. The aim of this article is to update readers on some recent advances that are starting to align the research and clinical functions of neuroimaging. As imaging becomes more accessible and affordable there is real promise that both clinicians and patients will begin to benefit more directly.
Nidotherapy: making the environment do the therapeutic work
Authors: Tyrer Peter , Bajaj Priya
Published: April 2005

Nidotherapy is the formal term introduced to describe the systematic manipulation of the physical and social environment to help achieve a better fit for a person with a persistent or permanent mental disorder. This approach is described in detail and its merits are compared with more conventional ways of dealing with such problems. This involves the creation of a certain number of terms that may be viewed as unnecessary jargon but help to shorten communication in an area where systematic monitored interventions are relatively uncommon.
Neuropsychological impairments in people with schizophrenia or bipolar disorder and their unaffected relatives
Authors: McIntosh Andrew M. , Harrison Lesley K. , Forrester Karen , Lawrie Stephen M. , Johnstone Eve C.
Published: April 2005

Background

Neuropsychological abnormalities in schizophrenia are well replicated and are present in unaffected relatives. Cognitive findings in bipolar disorder are less clearly established.

Aims

To examine the possibility that these abnormalities may provide a means by which the disorders might be separated and to clarify the associations of phenotypic expression and genetic liability.

Method

A neuropsychological test battery was administered to 50 control participants, 74 patients and 76 unaffected relatives recruited for the study. Patients included those with schizophrenia from families affected by schizophrenia alone, those with bipolar disorder from families affected by bipolar disorder alone and those with bipolar disorder from families affected by both disorders. Unaffected relatives were also recruited.

Results

Current, verbal and premorbid IQ were impaired in people with schizophrenia and in their close relatives. Memory was impaired in all patient and relative groups. Psychomotor performance and performance IQ were impaired in patients, regardless of diagnosis.

Conclusions

This study finds evidence that intellectual abnormalities are related to a genetic liability to schizophrenia. Abnormalities of memory appear to be related to an increased liability to psychosis in general. No impairment was specific to bipolar disorder.
Birth dimensions and risk of depression in adulthood: cohort study of Danish men born in 1953
Authors: Osler Merete , Nordentoft Merete , Andersen Anne-Marie Nybo
Published: April 2005

Background

Two British cohort studies have reported birth weight to be associated with self-reported depression in adulthood, even after adjustment for socio-economic factors.

Aims

To examine the relationship between birth dimensions and discharge from a psychiatric ward with a depression diagnosis in adulthood.

Method

A cohort of 10 753 male singletons born in Copenhagen, Denmark in 1953 and for whom birth certificates had been traced in 1965 were followed from 1969 until 2002, with record linkage for date of first admission to a psychiatric ward that led to a discharge diagnosis of depression.

Results

A total of 190 men, corresponding to 1.8% of the cohort, had a discharge diagnosis of depression. The Cox's regression analyses failed to show any association between birth dimensions (birth weight and ponderal index) and risk of psychiatric ward diagnosis of depression in adult life, before or after adjustment for social indicators at birth.

Conclusions

This study does not support the existence of a relation between birth dimensions and psychiatric ward admission for depression in adult men.
Mental health inequalities in Wales, UK: Multi–level investigation of the effect of area deprivation
Authors: Skapinakis Petros , Lewis Glyn , Araya Ricardo , Jones Kelvyn , Williams Gareth
Published: April 2005

Background

Geographical variation in the prevalence of common mental disorders has not been explained adequately.

Aims

To investigate whether regional mental health differences in Wales would persist after having taken into account the characteristics of individuals and regional social deprivation.

Method

Data from the 1998 Welsh Health Survey were used. Common mental disorders were assessed with the mental health index included in the Short-Form 36 health survey (SF–36). The data were analysed using a multi–level linear regression model.

Results

Of the total variance in the mental health index, 1.47% occurred at regional level (95% CI 0.56–2.38). Adjustment for individual characteristics did not explain the between-region variation. A higher area deprivation score was associated with a higher score on the mental health index.

Conclusions

Mental health differences in Wales are partly explained by the level of regional social deprivation.
Community study of knowledge of and attitude to mental illness in Nigeria
Authors: Gureje Oye , Lasebikan Victor O. , Ephraim-Oluwanuga Olusola , Olley Benjamin O. , Kola Lola
Published: April 2005

Background

The improvement of community tolerance of people with mental illness is important for their integration. Little is known about the knowledge of and attitude to mental illness in sub-Saharan Africa.

Aims

To determine the knowledge and attitudes of a representative community sample in Nigeria.

Method

A multistage, clustered sample of household respondents was studied in three states in the Yoruba-speaking parts of Nigeria (representing 22% of the national population). A total of 2040 individuals participated (response rate 74.2%).

Results

Poor knowledge of causation was common. Negative views of mental illness were widespread, with as many as 96.5% (s.d.=0.5) believing that people with mental illness are dangerous because of their violent behaviour. Most would not tolerate even basic social contacts with a mentally ill person: 82.7% (s.e.=1.3) would be afraid to have a conversation with a mentally ill person and only 16.9% (s.e.=0.9) would consider marrying one. Socio-demographic predictors of both poor knowledge and intolerant attitude were generally very few.

Conclusions

There is widespread stigmatisation of mental illness in the Nigerian community. Negative attitudes to mental illness may be fuelled by notions of causation that suggest that affected people are in some way responsible for their illness, and by fear.
Should we prescribe antidepressants to children?
Authors: Dubicka Bernadka , Goodyer Ian
Published: April 2005

In June last year, the committee on safety of medicines (CSM) advised against the use of paroxetine in depressed children and adolescents. This was subsequently followed by a similar warning regarding the use of other selective serotonin reuptake inhibitors (SSRIs), with the exception of fluoxetine (http://www.mhra.gov.uk/). The basis of this decision was a detailed review of both the published and the unpublished data. The latter were obtained from pharmaceutical companies who had not reported negative results from clinical trials to the medical community. The addition of the pharmaceutical industry data to published results exerted dramatic effects on the efficacy of available compounds. Thus with the exception of fluoxetine, the risks outweigh the benefits of the SSRIs in the treatment of childhood depression. In particular, there is evidence of a non-significant trend towards increased suicidality with most SSRIs compared with placebo. These findings have been supported by a further recent meta-analysis of the available published and unpublished data (Whittington et al, 2004). A review of the safety and efficacy of antidepressants in children and adolescents by Jureidini et al (2004) has also criticised the quality of reporting of the published trials. The review concluded that the benefits of SSRIs have been exaggerated, including those of fluoxetine, and the adverse effects have been downplayed. The authors suggest that psychological treatments are probably safer and more effective.