Occupational asthma in teachers.

BACKGROUND: Work-related asthma symptoms are common in teachers and teaching assistants, there are few studies evaluating their causes. AIMS: To identify causes of occupational asthma in teachers and teaching assistants referred to the Birmingham Occupational Lung Disease clinic 2000-20 using evaluation of serial Peak Expiratory Flow (PEF) records. METHODS: Teachers and teaching assistants with possible occupational asthma were asked to record PEF 2-hourly at home and work for 4 weeks. Their records were evaluated with the Oasys programme. Those with a positive score for any of the three scores (area between curves (ABC), timepoint and Oasys score from discriminant analysis) were included. Repeat records were made as indicated to help identify the cause and the effects of remedial actions. RESULTS: Thirty-eight teachers or teaching assistants met the inclusion criteria with all three Oasys scores positive in 24, 2/3 scores in nine and 1/3 in five. The building was the likely cause in 17 (in new builds particularly acrylates from carpet adhesives and in old buildings mould and construction dust), bystander exposure to agents in the schools in 12 (cleaning agents, acrylates from photocopiers and chloramines from indoor pools) and materials used in the classroom in 9 (most commonly MDF in design and technology classes). We illustrate how the PEF records helped identify the cause. CONCLUSIONS: Oasys analysis of PEF records is a useful method of evaluating occupational asthma in teachers and identified difficult to confirm causes where successful remediation or redeployment was achieved.

Disability and disability benefit seeking in chronic low back pain.

BACKGROUND: Numerous studies suggest psychosocial factors contribute to functional disability in patients with chronic low back pain (CLBP). However, less is known about the association of psychosocial factors, such as depression, with seeking medical disability benefits and their prevalence in benefit seekers compared with patients already receiving such payments. AIMS: To determine if characteristics of disability benefit seekers differ from patients receiving disability benefits and if both differ from patients not dependent on such payments. METHODS: Questionnaire data on pain, health-related quality of life, depression, social support, substance abuse, adverse childhood experiences and disability seeking were obtained from CLBP respondents recruited at 10 primary care clinics throughout Texas. A multinomial logistic regression model was computed using variables significantly associated with disability status and pain severity in univariate models. RESULTS: There were 213 participants. In full models, compared with those not on disability benefits, only depression symptoms were significantly associated with seeking disability benefits (odds ratio [OR] = 1.13; 95% confidence interval [CI] 1.01-1.26) and only duration of pain was significantly associated with being on such benefits (OR = 1.05; 95% CI 1.01-1.09). CONCLUSIONS: Patient characteristics differ between disability benefit seekers and those established on disability benefit payments. Depression may be a modifiable correlate of disability benefit seeking that if treated may reduce the number of patients who eventually come to depend on disability benefits. Additional data collection involving other pain syndromes is warranted to determine if these results are unique to CLBP or apply to other painful conditions.

Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease.

Darier disease (DD) is an autosomal-dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently we constructed a 2.4-Mb, P1-derived artificial chromosome contig spanning the DD candidate region on chromosome 12q23-24.1. After screening several genes that mapped to this region, we identified mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca2(+)-ATPase type 2 isoform (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were identified, including frameshift deletions, in-frame deletions or insertions, splice-site mutations and non-conservative missense mutations in functional domains. Our results demonstrate that mutations in ATP2A2 cause DD and disclose a role for this pump in a Ca(2+)-signalling pathway regulating cell-to-cell adhesion and differentiation of the epidermis.

A novel missense mutation in GJB2, p.Tyr65His, causes severe Vohwinkel syndrome.

Gap junctions are intercellular channels which are permeable to ions and small molecules up to about 1 kDa in size. They are prominent in the skin, but their precise function there is largely unknown. Mutations in skin-expressed gap junction genes disrupt epidermal growth and differentiation. A relatively minor epidermal connexin, connexin 26 (Cx26), is associated with a wide variety of phenotypes, each specifically associated with a particular amino acid residue. How the different mutations in GJB2 lead to such distinctive phenotypes is poorly understood. Analysis of new GJB2 mutations can shed new light on pathogenesis and the apparently vital role of Cx26 in maintaining epidermal integrity.

Medium-density fibreboard and occupational asthma. A case series.

BACKGROUND: Medium-density fibreboard (MDF) is a wood composite material, composed primarily of softwood, bonded with a synthetic formaldehyde-based resin. It is increasingly used, as it has various advantages over natural woods. METHODS: Enquiry of the national reporting scheme data and three case reports were used to further the evidence base linking this exposure to occupational asthma (OA). RESULTS: From 1991 to 2007, 21 cases of occupational sensitization to MDF were reported to the UK voluntary reporting scheme, Surveillance of Work Related Occupational Respiratory Disease (SWORD): 18 reported as occupational asthma (OA) and 3 as occupational rhinitis. All workers were male, with a mean age of 48 years, working in education, furniture manufacturing or joinery among other employments. CONCLUSIONS: Whilst reporting scheme data identified relatively small numbers of cases of OA likely to be due to MDF, the evidence base supporting this link is generally lacking. The three cases presented, where OA was attributed to MDF exposure, add to this evidence.

The neuropsychiatric phenotype in Darier disease.

BACKGROUND: Darier disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. It is caused by mutations in a single gene, ATP2A2, which is expressed in the skin and brain. OBJECTIVES: To conduct the first systematic investigation of the neuropsychiatric phenotype in DD. METHODS: One hundred unrelated individuals with DD were assessed using a battery of standardized neuropsychiatric measures. Data were also obtained on a number of clinical features of DD. RESULTS: Individuals with DD were found to have high lifetime rates of mood disorders (50%), specifically major depression (30%) and bipolar disorder (4%), and suicide attempts (13%) and suicidal thoughts (31%). These were more common in DD when compared with general population data. The prevalence of epilepsy (3%) in the sample was also higher than the prevalence in the general population. There was no consistent association of specific dermatological features of DD and presence of psychiatric features. CONCLUSIONS: These findings highlight the need for clinicians to assess and recognize neuropsychiatric symptoms in DD. The results do not suggest that neuropsychiatric symptoms are simply a psychological reaction to having a skin disease, but are consistent with the pleiotropy hypothesis that mutations in the ATP2A2 gene, in addition to causing DD, confer susceptibility to neuropsychiatric features. Further research is needed to investigate genotype-phenotype correlations between the types and/or locations of pathogenic mutations within ATP2A2 and the expressed neuropsychiatric phenotypes.

Career choices in dermatology.

Reforms to both undergraduate and postgraduate training have resulted in limited exposure to clinical dermatology, and therefore we need to target advice and clinical attachments to the most appropriate stages of training to ensure that dermatology is considered as a career option by medical students. A questionnaire survey was undertaken to determine when and how doctors chose their career in dermatology. An electronic questionnaire was sent to 709 dermatologists (response rate 44%). Of the respondents, 49% considered dermatology after medical school attachment and 61% were influenced by the jobs they had done as a pre-registration house officer (PRHO) or senior house officer (SHO). Careers advice was lacking, with only 11% receiving it while at medical school and 29% during their PRHO/SHO years. Contact with an inspiring clinician was the most influential factor in choosing dermatology. Both medical students and junior doctors, should have opportunities to learn from and work with clinical dermatologists.

Poromas and porokeratosis in a patient treated for solid-organ and haematological malignancies.

We describe a patient with previous solid-organ (testicular, oesophageal) and haematological (acute myeloid leukaemia) malignancies, in whom chronic cutaneous graft-versus-host disease was complicated by poromas and porokeratosis. Chemotherapy, total body irradiation, longstanding immunosuppression and ultraviolet radiation may all have played a part in the pathogenesis of the skin tumours.

Audit of dermatological content of U.K. undergraduate curricula.

BACKGROUND: Recommendations for the dermatology content (learning outcomes) of the core undergraduate curriculum were sent to all U.K. medical schools in June 2006. OBJECTIVE: To carry out an audit of the content of the core curriculum in each U.K. medical school against the recommendations for a core undergraduate dermatology curriculum (the criteria) published by the British Association of Dermatologists, to identify areas of good practice and to gather evidence for developing the learning and teaching of dermatology. METHODS: A questionnaire was circulated to the dermatology teaching leads of all U.K. medical schools (29) and one Irish medical school. Questions which the teaching leads were unable to answer were sent to the relevant deans and responses incorporated into the results. All curricula should include the essential learning outcomes that focus on clinical skills; as this was an audit to benchmark current practice, we did not set standards for the other recommendations for a core curriculum. RESULTS: Replies were received from teaching leads in 29 of the 30 medical schools and from 16 of the deans. Essential clinical skills such as taking a dermatological history and examining the skin were included in the curricula of most, but not all, medical schools. Areas of good practice include teaching on tumours, acne and psoriasis, but we found some surprising omissions including the diagnosis of meningococcaemia. Our data suggest that some students have little exposure to dermatology, but dermatology teaching takes place in secondary care in all medical schools. Knowledge-based assessments are used by 27 medical schools. CONCLUSIONS: Curricula should be strengthened so that the recommended learning outcomes feature in the core curricula of all medical schools. Teaching leads in all specialties, including those in the community, should communicate so that learning and teaching are integrated horizontally and vertically. The results should provide a baseline for future audits.

Care of patients with psoriasis: an audit of U.K. services in secondary care.

BACKGROUND: Medical professionals require data about the structure and delivery of dermatological services in primary and secondary care in order to identify and tackle variations in standards and monitor the impact of healthcare reforms. The British Association of Dermatologists (BAD) commissioned an audit of the provision of care for patients with psoriasis. OBJECTIVES: To assess the staffing and facilities in dermatology units in the U.K. with a focus on the provision of care for patients with psoriasis. METHODS: Data were collected from 100 dermatology units in the U.K. for 1 year using a questionnaire and a web-based collection system. RESULTS: Key results are as follows. Eighteen per cent (18/98) of units had fewer than 2.0 whole-time equivalent consultants and 20% had no specialist dermatology nurse. Only 23% of units collected diagnostic data on outpatients, and half were unable to supply details about the number of attendances for psoriasis. Seventy-seven units reported admitting patients to dedicated dermatology beds, general medical beds, or both; three-quarters of units had access to dedicated adult dermatology beds. Pharmacy services were not always available for dermatology patients. Only 21 units (21%) had dedicated clinics for patients with psoriasis and 56% of units lacked a clinical psychology service willing to accept adult dermatology patients; 59% (55/93) lacked psychological services for children. Fifty-five per cent had no systemic drug monitoring clinic. Phototherapy was run by dermatology nurses in 93% (88/95) of the units and by physiotherapists in 11% (10/94). Biologics for psoriasis were prescribed in 75% (73/97) of units and in 88% (64/73) of these the BAD guidelines for the use of biologics were known to be followed. Of the seventy-three units prescribing biologic therapies, 64% had a nurse trained in the assessment and administration of biologics, 71% had facilities for outpatient infusions (e.g. for infliximab) and 39% were restricted in prescribing biologic agents because of financial constraints. A quality-of-life score was either inadequately or never recorded in outpatient records in 81% of units, increasing to 88% for inpatient records. The Psoriasis Area and Severity Index score was inadequately or never recorded in 79% of outpatient records and 82% of inpatient records. CONCLUSIONS: Units varied in their capacity to meet BAD guidelines and standards. Among the most significant deficiencies identified were a shortage of specialist dermatology nurses, treatment delivery by untrained nurses and financial constraints on the prescription of biologics for psoriasis. Gaps in data collection and record keeping jeopardize efforts to improve standards of care.

Point-of-care controls for nosocomial legionellosis combined with chlorine dioxide potable water decontamination: a two-year survey at a Welsh teaching hospital.

This study reports a two-year programme of attempted eradication of Legionella colonization in the potable water supply of a 1000-bed tertiary care teaching hospital in Wales. There was a simultaneous, point-of-care, sterile-water-only policy for all intensive care units (ICU) and bone marrow and renal transplant units in order to prevent acquisition of nosocomial Legionnaires' disease. The programme was initiated following a case of nosocomial pneumonia caused by Legionella pneumophila serogroup 1-Bellingham-like genotype A on the cardiac ICU. The case occurred 14 days after mitral and aortic valve replacement surgery. Clinical and epidemiological investigations implicated aspiration of hospital potable water as the mechanism of infection. Despite interventions with chlorine dioxide costing over 25000 UK pounds per annum, Legionella has remained persistently present in significant numbers (up to 20000 colony forming units/L) and with little reduction in the number of positive sites. Two further cases of nosocomial disease occurred over the following two-year period; in one case, aspiration of tap water was implicated again, and in the other case, instillation of contaminated water into the right main bronchus via a misplaced nasogastric tube was implicated. These cases arose because of inadvertent non-compliance with the sterile-water-only policy in high-risk locations. Enhanced clinical surveillance over the same two-year period detected no other cases of nosocomial disease. This study suggests that attempts at eradication of Legionella spp. from complex water systems may not be a cost-effective measure for prevention of nosocomial infections, and to the best of our knowledge is the first study from the UK to suggest that the introduction of a sterile-water-only policy for ICUs and other high-risk units may be a more cost-effective approach.

Mosaicism for ATP2A2 mutations causes segmental Darier's disease.

Epidermal naevi are localized malformations of the epidermis consisting of verrucoid scaly papules and plaques following Blaschko's lines. Genetic mosaicism has been proposed to underlie the development of linear epidermal naevi. Rarely, epidermal naevi show acantholytic histology similar to Darier's disease, a dominantly inherited skin condition characterized by widespread warty papules. As patients with acantholytic dyskeratotic naevi often give a history of worsening after sun exposure and the lesions are typical of Darier's disease, numerous authors have proposed that these patients have segmental Darier's disease. The postulated relationship has not been proven, however. Recently, we identified ATP2A2, which encodes the sarco/endoplasmic reticulum Ca(2+) ATPase isoform 2 as the defective gene in Darier's disease. In this report, we investigated the involvement of ATP2A2 in acantholytic dyskeratotic naevi following Blaschko's lines in two patients. We identified a nonsense mutation (Y894X) in the first patient and a nonconservative glycine to arginine mutation at codon 769 (G769R) in the other patient. These mutations were present in affected skin, and were not detected in unaffected skin or in leukocytes. We conclude that acantholytic dyskeratotic naevi can arise from a somatic mutation in ATP2A2. These individuals are mosaics for the mutation, but the risk of transmission of generalized Darier's disease will depend on whether the germline is affected. Our findings provide further evidence that Blaschko's lines do reflect genetic mosaicism and that the term acantholytic dyskeratotic naevus might be replaced in the future by segmental Darier's disease induced by postzygotic mosaicism. J Invest Dermatol 115:1144-1147 2000

Pigment change and melanocyte distribution in guinea pig skin after cutaneous freeze injury.

Cryosurgery has been recommended for the treatment of cutaneous neoplasms, including benign and malignant melanocytic tumors. The main side effect of this treatment is pigment disruption which may be prolonged. There are no quantitative studies on melanocyte distribution after freeze injury. In this study the effect of standardized freeze times on melanocytes in guinea pig skin (tricolored) is described at the anatomic level and at the light and electron microscopic level. Melanocytes are quantified in epidermal sheets following dopa staining at 1-, 2-, and 3-month intervals after freezing. All the lesions were initially hypopigmented with a peripheral rim of hyperpigmentation. This was a transient phenomenon associated with an absence of melanocytes. Pigment migrated into the lesions so that after 3 months all the lesions on black skin were diffusely hyperpigmented. Pigment was slower to return to the red skin. Hair follicles were destroyed in the center of the lesion. The epidermal sheets demonstrated that the hyperpigmentation was an epidermal phenomenon and was associated with increased numbers of melanocytes (p less than 0.001). These melanocytes were distributed evenly throughout the lesion in contrast to the irregular distribution in normal skin.

Should inhaled corticosteroids be used in the long term treatment of chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease (COPD) is a progressive disease with alveolar destruction (emphysema) and bronchiolar fibrosis (obstructive bronchitis) in variable proportions. Reducing disease progression, as assessed by forced expiratory volume in I second (FEV1) decline, health-related quality of life, exacerbation rate and mortality, is a more realistic outcome than physiological improvement. This paper reviews all the published studies of at least 100 patients followed for at least 2 years. Studies have included patients with mild COPD (Copenhagen City Lung Study) to advanced symptomatic disease [Inhaled Steroids in Obstructive Lung Disease (ISOLDE)], with 2 studies of those with relatively early symptoms [European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP) and Lung Health-21. Exacerbation frequency, and probably severity, are reduced by high dose inhaled corticosteroids. Exacerbations are only frequent in more advanced disease, limiting the use of this outcome in EUROSCOP and Lung Health-2. Exacerbations are associated with reduced health-related quality of life. ISOLDE clearly showed a reduced rate in decline of the disease-specific St George's Respiratory Questionnaire with fluticasone propionate, partly related to the reduced exacerbations. The symptom component of the score showed the greatest difference between placebo and fluticasone propionate. None of the larger studies were able to reproduce the statistically significant reduction in the rate of decline in FEV1 suggested by the smaller, earlier studies. This might at least in part be as a result of the statistical modelling used which cannot adequately compensate for those with more rapidly progressive disease dropping out earlier. The equivalent doses of inhaled corticosteroids differed approximately fivefold between the major studies. The more positive results were obtained with higher doses. Oropharyngeal adverse effects were similar to those seen in patients with asthma; bruising was increased in one study with budesonide, otherwise adverse effects were similar to placebo. Bone loss was specifically studied in subgroups of patients in EUROSCOP and Lung Health-2. Budesonide 800 microg/day was associated with less bone loss than placebo, whereas triamcinolone 1200 microg/day was associated with excess bone loss. High dose inhaled corticosteroids have a favourable risk/benefit ratio in patients with advanced disease, particularly those with frequent exacerbations, and no benefit for those with very mild disease. It is not possible from the data to make firm recommendations for the important intermediate group where delaying progression is likely to lead to greatest benefit. I believe high dose inhaled steroids are warranted for those with intermediate severity COPD, who have frequent exacerbations or significant COPD-related symptoms.

Monitoring the bacteriological quality of potable waters in hospital.

We report a survey of the bacteriological quality of potable waters from hospitals. In the 12-month period February 1986 to January 1987, 646 samples were examined from 25 hospitals. Coliforms were isolated from eight (1.2%) samples, received from three hospitals. These hospitals did not, therefore, satisfy the European Community (EC) directive on potable water quality. Three hundred and four (47%) samples had total viable counts higher than the guidelines given in the EC directive on potable waters. Thirteen (52%) of hospitals surveyed submitted at least one unsatisfactory sample and six (24%) submitted more than 50% unsatisfactory samples. Water quality was generally poorer in the summer and autumn. Estimation of the total viable count is an inexpensive and simple method for monitoring the microbial quality of hospital waters.

An evaluation of two primary care interventions for alcohol abuse among Mexican-American patients.

AIMS: This study examined the effects of two primary care interventions (a physician intervention and a clinic-based psychoeducational group) on drinking patterns, psychosocial problems and blood test results (MCV, GGT, SGOT and SGPT). DESIGN: Subjects were randomized into one of four treatment groups: physician intervention, psychoeducation, both interventions, or no intervention. Follow-up data were collected at 12 and 18 months. SETTING: Subjects were recruited from a family practice outpatient clinic managed by a public hospital. PARTICIPANTS: Included 175 Mexican-American female and male primary care patients who screened positive for alcohol abuse or dependence. These patients were not seeking help for alcohol problems. INTERVENTIONS: Included a brief physician intervention and a 6-week patient psychoeducational group. MEASUREMENTS: The Diagnostic Interview Schedule assessed subjects for alcohol abuse; the Addiction Severity Index measured alcohol-related problems, including psychosocial issues. FINDINGS: All four treatment groups demonstrated significant improvement over time, with few differences between intervention and control groups. CONCLUSIONS: Assessment can be confounded with brief interventions; future investigators should use non-assessed control groups.