A glycogen synthase 1 mutation associated with equine polysaccharide storage myopathy and exertional rhabdomyolysis occurs in a variety of UK breeds.

REASONS FOR PERFORMING STUDY: A glycogen synthase (GYS1) mutation has been described in horses with histopathological evidence of polysaccharide storage myopathy (PSSM) in the USA. It is unknown whether the same mutation is present in horses from the UK. OBJECTIVES: To determine whether the GYS1 mutation occurs in UK horses with histopathological evidence of PSSM and exertional rhabdomyolysis. HYPOTHESIS: The R309H GYS1 mutation is present in a variety of UK horse breeds and that the mutation is commonly associated with exertional rhabdomyolysis. METHODS: DNA was extracted from 47 muscle or blood samples from UK horses with histories of exertional rhabdomyolysis in which muscle biopsy diagnosis had been pursued. The proportions of GYS1 mutation positive cases were compared among histopathologically defined groups. In addition, breeds that carried the GYS1 mutation were identified from a total of 37 grade 2 (amylase-resistant) PSSM cases. RESULTS: Of 47 horses with exertional rhabdomyolysis in which a muscle biopsy diagnosis was pursued, 10 (21%) carried the GYS1 mutation. The mutation was only found in horses with grade 2 PSSM (i.e. not in horses with normal, idiopathic myopathy or grade 1 PSSM biopsy samples). In total, the GYS1 mutation was found in 24/37 (65%) of grade 2 PSSM cases. A variety of breeds, including Quarter Horse, Appaloosa, Warmblood, Connemara-cross, Cob, Polo Pony and Thoroughbred cross carried the mutation. CONCLUSIONS: The GYS1 mutation is an important cause of exertional rhabdomyolysis of UK horse breeds but does not account for all forms of PSSM. POTENTIAL RELEVANCE: Genotyping is recommended in cases of exertional rhabdomyolysis, prior to or in combination with, muscle biopsy. However a significant proportion of horses with histopathological evidence of PSSM and/or exertional rhabdomyolysis have different diseases.

Storage-associated artefact in equine muscle biopsy samples.

REASONS FOR PERFORMING STUDY: Muscle biopsy is increasingly used in equine veterinary practice for investigating exertional, inflammatory or immune mediated myopathies and unexplained muscle atrophy. Although formalin-fixed samples are often used, for complete evaluation, fresh-frozen tissue is required. Freezing muscle in veterinary practice is impractical: samples sent to specialist laboratories for processing are therefore susceptible to delays, potentially leading to artefact and compromising histological interpretation. HYPOTHESIS: Altered temperature, duration and hydration status influence the severity of storage-induced artefact in equine muscle. METHODS: Skeletal muscle obtained immediately post euthanasia was divided into 6 independent samples from each of 8 horses. One sample per horse was frozen immediately in isopentane precooled in liquid nitrogen. Additional samples were stored in conditions designed to mimic possible situations encountered in practice, including increased storage times, temperature and hydration status. Following storage, stored samples were frozen as before. Cryosections were stained using haematoxylin and eosin and ranked for artefact on 2 occasions by 2 blinded observers. The best samples were processed subsequently with a panel of routine stains and immunolabelled for collagen V to enable the measurement of minimum fibre diameters. RESULTS: Both prolonged storage and increased hydration resulted in more storage-associated artefact. Samples stored for 24 h chilled on dry gauze were ranked higher than those stored on damp gauze; however, a panel of routinely-used histochemical staining techniques was unaffected by chilled 24 h storage. There was no significant effect of storage on mean fibre diameter; however, both chilled dry and damp storage for 24 h caused a significant increase in fibre-size variability. CONCLUSION AND POTENTIAL RELEVANCE: Caution should be exercised when interpreting fibre size profiles in shipped samples. Equine muscle biopsy samples are optimally shipped in dry gauze, sealed in plastic containers and shipped on ice packs to be processed within 24 h and can thus be interpreted by the receiving laboratory with minimal artefact.

Effects of exercise on tenocyte cellularity and tenocyte nuclear morphology in immature and mature equine digital tendons.

REASON FOR PERFORMING STUDY: The injury-prone, energy-storing equine superficial digital flexor tendon (SDFT) of the mature performance horse has a limited ability to respond to exercise in contrast with the noninjury-prone, anatomically opposing common digital extensor tendon (CDET). Previous studies have indicated low levels of cellular activity in the mature SDFT, but in foal tendons the tenocytes may still have the ability to adapt positively to increased exercise. OBJECTIVES: To measure tenocyte densities and types in histological sections from the SDFT and CDET of horses from controlled long-term, short-term and foal exercise studies. METHODS: Specimens were collected from mid-metacarpal segments of the CDET and SDFT for each horse and processed for histology; central and peripheral regions of the SDFT cross-section were analysed separately (SDFTc, SDFTp). Tenocyte nuclei were counted in a total area of 1.59 mm(2) for each tendon region in each horse. Each nucleus was classified as type 1 (elongate and thin), type 2 (ovoid and plump) or type 3 (chondrocyte-like); type 1 cells are proposed to be less synthetically active than type 2 cells. RESULTS: No significant differences were noted between exercise and control groups in any of the studies, with the exception of an exercise-related reduction in the proportion of type 1 tenocytes for all tendons combined in the long-term study. There were tendon- and site-specific differences in tenocyte densities and proportions of type 1 and 2 cells in all 3 studies. CONCLUSIONS AND POTENTIAL RELEVANCE: There was no indication that exercise increased tenocyte density or proportions of the (theoretically) more active type 2 cells in immature horses (short-term and foal studies), perhaps because the training regimens did not achieve certain threshold strain levels. In the foal study these findings can still be interpreted positively as evidence that the training regimen did not induce subclinical damage.

Inequalities in dementia care across Europe: key findings of the Facing Dementia Survey.

The Facing Dementia Survey was undertaken to assess the awareness of and behaviours surrounding Alzheimer's disease (AD) and dementia among all key stakeholders in Europe. Interviews were conducted with more than 2500 persons, including caregivers, members of the general population, physicians, persons with AD and influencers of health care policy. Four key messages emerged from the results. First, AD often remains undiagnosed until symptoms become moderate or severe. This delay may be because of the difficulty of recognising the symptoms of early AD and the attribution of symptoms to so-called normal ageing, the fear of AD common among older people, inadequate screening tools for use by physicians and/or a delay in the confirmation of the diagnosis once suspicion is raised. Second, a majority of respondents perceive their governments as indifferent to the economic, social and treatment burdens associated with AD. Third, a substantial majority of caregivers, physicians and the general population appreciate the wide-ranging impact that AD can have on the quality of life of people who suffer from it and their informal caregivers. While most caregivers reported life-changing negative effects, a few also noted some positive aspects to their experience. Finally, survey results revealed that most caregivers and members of the general public do not have sufficient information about the benefits of treatment and care. The findings of the Facing Dementia Survey support the development of an agenda for change in dementia care across Europe.

A multi-state outbreak of tuberculosis among members of a highly mobile social network: implications for tuberculosis elimination.

SETTING: Baltimore, Maryland. OBJECTIVE: To describe a tuberculosis (TB) outbreak among a highly mobile population and the efforts required to control it. DESIGN: Epidemiologic outbreak investigation. RESULTS: Between June 1998 and January 2000, 20 TB outbreak cases were identified, of which 18 were culture-confirmed. Seventeen isolates of Mycobacterium tuberculosis had an identical 11-band DNA fingerprint; another isolate had one additional band and was considered a match. Two cases were diagnosed in New York City; another patient lived primarily in Atlanta, but was diagnosed in Baltimore. Persons in the outbreak were predominantly young (median age 24 years), black, male, infected with the human immunodeficiency virus (HIV), and gay, transvestite or transsexual. Activities common among many TB cases included attending two nightclubs, membership in one of three social 'Houses', attending balls or pageants in East Coast cities, marijuana use, and prostitution. Community outreach, extended contact tracing, DNA fingerprinting, directly-observed therapy, and expanded use of preventive therapy were utilized to assess and control the outbreak. During the outbreak period the Baltimore City TB rate declined by 10%. However, additional public health personnel were required to control the outbreak, resulting in a 17% increase in TB clinic staff. CONCLUSION: As TB rates decline, remaining cases are likely to occur in difficult-to-reach populations. Increased resources per case of TB treated will be required to eliminate TB.

Specific gravity adjustment of urine analysis results.

Analysis of urine samples for compounds such as lead, phenol, or 4,4'-methylene bis (2-chloroaniline) (MBOCA) are often adjusted for specific gravity following a recommendation in a NIOSH Benzene Criteria Document. The adjustment normalizes all results to a specific gravity of 1.024 by multiplying the analytical result in microgram/liter by 24/G where G is the last 2 digits of the specific gravity of the urine sample. The adjustment calculation is based on a suggestion by Levine and Fahy, who found that the urine solids content is roughly proportional to 24/G. We believe this adjustment to be inappropriate based on the following considerations.

Evidence for an androgen-binding component in the cytosol of the human term placenta.

The present communication describes a specific, high-affinity (Kd = 1.9 +/- 0.21 x 10(-9)M; n = 3) binding component for dihydrotestosterone present in the high-speed, hormone-stripped cytosol fraction of the human term placenta. In order to delineate the nature of this substance, the synthetic steroids R1881 (progesterone and androgen receptor specific) and R5020 (progesterone receptor specific) were employed. Minimal binding of H3-R5020 was observed; however, H3-R1881 was found to bind with a Kd = 0.6 +/- 0.18 x 10(-9)M (n = 3). The relative displacing ability of R5020 for H3-R1881 was only 1.3%, substantiating the presence of an androgen binder and negating the presence of a significant level of a progesterone-binding component. Evidence that the binder is of placental origin and does not result from blood contamination includes no significant binding of H3-R1881 to pregnancy serum, binder thermolability at 45 degrees C, and precipitation of the binder by ammonium sulfate at 30% saturation. Speculations as to the receptor or receptor-like nature of the binder are presented.

The identification and elimination of a potential lead hazard in an urban park.

During development of a park in Oakland, California, a potential public helath hazard due to lead in the soil (approximately 1,000 to 100,000 ppm) was identified through cooperative sampling and analysis efforts of the staffs at the county and state health departments. Analysis of samples collected at various locations and depths in the park, coupled with a three-dimensional model of the lead values obtained, indicated steps necessary to eliminate the hazard. The county undertook the abatement program, and with the elimination of the health hazard, the park development has been completed. Concomitant blood lead screening of neighborhood children failed to establish the park as a source of elevated lead in any of the children tested.