Greater muscle damage in athletes with ACTN3 R577X (RS1815739) gene polymorphism after an ultra-endurance race: a pilot study.

In this study, we aimed to investigate the influence of ACTN3 R577X gene polymorphism on muscle damage responses in athletes competing in an ultra-endurance race. Twenty moderate to well-trained ultra-runners who had entered in an official 37.1 km adventure race (22.1 km mountain biking, 10.9 km trekking, 4.1 km water trekking, 30 m rope course, and orienteering) volunteered for the study. Blood samples were collected for genotyping and analysis of muscle protein levels before and after the race. Percentage changes (pre- to post-race) of serum myoglobin [XX = 5,377% vs. RX/RR = 1,666%; P = 0.005, effect size (ES) = 1.73], creatine kinase (XX = 836.5% vs. RX/RR = 455%; P = 0.04, ES = 1.29), lactate dehydrogenase (XX = 82% vs. RX/RR = 65%; P = 0.002, ES = 1.61), and aspartate aminotransferase (XX = 148% vs. RX/RR = 75%; P = 0.02, ES = 1.77) were significantly greater for XX than RX/RR genotypes. ES analysis confirmed a large magnitude of muscle damage in XX genotype ultra-runners. Therefore, athletes with the ACTN3 577XX genotype experienced more muscle damage after an adventure race. This suggests that ultra-runners with alpha-actinin-3 deficiency may be more susceptible to rhabdomyolysis and associated health complications during ultra-endurance competitions.

Multiple horizontally acquired genes from fungal and prokaryotic donors encode cellulolytic enzymes in the bdelloid rotifer Adineta ricciae.

The bdelloid rotifer, Adineta ricciae, an anhydrobiotic microinvertebrate, exhibits a high rate of horizontal gene transfer (HGT), with as much as 10% of its transcriptome being of foreign origin. Approximately 80% of these foreign transcripts are involved in metabolic processes, and therefore bdelloids represent a useful model for assessing the contribution of HGT to biochemical diversity. To validate this concept, we focused on cellulose digestion, an unusual activity in animals, which is represented by at least 16 genes encoding cellulolytic enzymes in A. ricciae. These genes have been acquired from a variety of different donor organisms among the bacteria and fungi, demonstrating that bdelloids use diverse genetic resources to construct a novel biochemical pathway. A variable complement of the cellulolytic gene set was found in five other bdelloid species, indicating a dynamic process of gene acquisition, duplication and loss during bdelloid evolution. For example, in A. ricciae, gene duplications have led to the formation of three copies of a gene encoding a GH45 family glycoside hydrolase, at least one of which encodes a functional enzyme; all three of these gene copies are present in a close relative, Adineta vaga, but only one copy was found in each of four Rotaria species. Furthermore, analysis of expression levels of the cellulolytic genes suggests that a bacterial-origin cellobiase is upregulated upon desiccation. In summary, bdelloid rotifers have apparently developed cellulolytic functions by the acquisition and domestication of multiple foreign genes.

Hypovitaminosis D among rheumatology outpatients in clinical practice.

OBJECTIVES: A role for vitamin D in the pathogenesis of autoimmune and inflammatory diseases is emerging. We undertook an audit of 25-hydroxyvitamin D (25OHD) investigation and treatment in rheumatology outpatients. METHODS: Serum 25OHD requests were matched to electronic medical records from rheumatology and metabolic bone clinics (April 2006-March 2007). Data were analysed separately for two groups, 'Documented osteoporosis/osteopaenia' (Group 1) and 'General rheumatology outpatients' (Group 2, sub-divided by diagnosis). Hypovitaminosis D was defined by 25OHD levels <50 nmol/l. Values were compared with healthy adults to calculate geometric z-scores. RESULTS: A total of 263 patients were included (Group 1, n = 122; Group 2, n = 141) with an overall median 25OHD of 44 nmol/l. The 25OHD level among general rheumatology patients (median 39 nmol/l, mean z score -1.2, was statistically significantly lower than among osteoporotic/osteopaenic patients (median 49 nmol/l, mean z score of -0.9, p < 0.05 for the difference). 25OHD was lower in inflammatory arthritis and chronic pain/fibromyalgia than in other groups. Prescribing was recorded in 100 in Group 1 (of whom 95% were prescribed calcium/800 IU cholecalciferol) and 83 in Group 2 (91% calcium/800 IU). Only 31% of the patients with 25OHD <50 nmol/l would have been identified using general guidelines for screening patients at 'high risk' of hypovitaminosis D. CONCLUSIONS: Improved guidelines for managing hypovitaminosis D in rheumatology patients are needed. We found a high prevalence of hypovitaminosis D among secondary care patients in rheumatology and widespread supplementation with 800 IU cholecalciferol. Substantially reduced levels of serum 25OHD were identified among patients with inflammatory arthritis and chronic pain.

Why do we choose rheumatology? Implications for future recruitment--results of the 2006 UK Trainee Survey.

OBJECTIVES: Against changes to junior doctor career structure under MMC (Modernizing Medical Careers), and uncertainty about the future place of rheumatology, we explored critical factors in choice of rheumatology as a speciality, and asked what factors might govern choices of prospective trainees. Using these data, we developed suggestions to enhance future recruitment. METHODS: A postal survey was sent to rheumatology specialist registrars (SpRs) on the Joint Committee for Higher Medical Training (JCHMT) database between December 2005 and January 2006, and concurrently by e-mail to the Rheumatologists at Training e-mail list. RESULTS: Seventy-three percent (165/227) of trainees responded. Of them, 89.1% had previous senior house officer (SHO) experience in rheumatology and 81.8% made a career decision in favour of rheumatology during their SHO post. The top four ranked factors influencing choice of rheumatology were SHO experience, subject matter, inspirational consultants and lifestyle aspects; 89.1% would still choose rheumatology now. Factors felt to be negatively influencing future trainees came under three key themes: poor student or postgraduate exposure, employment and service delivery issues (including concern over the future place of rheumatology in primary vs secondary care), and perceived poor profile of rheumatology. Factors positively influencing future candidates were subject matter, work/life balance and prior exposure to the speciality. CONCLUSIONS: Early postgraduate experience is key to choice of speciality. An overwhelming majority of trainees decide speciality during SHO experience. With ongoing changes in career structure, it is critical that rheumatology is incorporated into foundation and speciality training programmes and essential that continued measures are taken to improve the image of rheumatology.

Astrophysical reaction rate for the neutron-generator reaction 13C(alpha,n)16O in asymptotic giant branch stars.

The reaction 13C(alpha,n) is considered to be the main source of neutrons for the s process in asymptotic giant branch stars. At low energies, the cross section is dominated by the 1/2+ 6.356 MeV subthreshold resonance in (17)O whose contribution at stellar temperatures is uncertain by a factor of 10. In this work, we performed the most precise determination of the low-energy astrophysical S factor using the indirect asymptotic normalization (ANC) technique. The alpha-particle ANC for the subthreshold state has been measured using the sub-Coulomb alpha-transfer reaction ((6)Li,d). Using the determined ANC, we calculated S(0), which turns out to be an order of magnitude smaller than in the nuclear astrophysics compilation of reaction rates.

Referrals to hospital-based rheumatology and orthopaedic services: seeking direction.

OBJECTIVES: While both community and hospital-based services strive to cope with the considerable burden posed by musculoskeletal disorders, multidisciplinary-led, integrated approaches are frequently lacking. It has been suggested that referrals to musculoskeletal services are frequently misdirected to an orthopaedic surgeon when non-surgical advice/intervention is warranted, reducing the efficiency of hospital-based services and potentially affecting quality of care. Triage of referrals may help to prevent this, but this system is dependent upon accurate and thorough information being provided in the referral letter. Our aim was to assess the feasibility of triage of musculoskeletal referrals to rheumatology and orthopaedic services at a large teaching hospital. METHODS: One thousand and eighty-seven consecutive referral letters to orthopaedic and rheumatology services were reviewed by a consultant rheumatologist. Letters were assessed for both basic content and the appropriate destination for that referral. In order to evaluate the accuracy of the assessor's prediction of the most appropriate destination of the referrals, the number of patients who were ultimately listed for surgical intervention was calculated in a random sample of orthopaedic referrals, 1 yr after the initial hospital appointment was requested. RESULTS: Six hundred and eighty-two referrals were to orthopaedics and 393 to rheumatology. Referrals relating to spinal pain were excluded. The content of letters was scant and no diagnosis was volunteered in 63.4% of referrals. Fifty-eight per cent of referrals to orthopaedics were considered appropriate; 27% of referrals to orthopaedics were defined as 'should definitely see a rheumatologist' (12%) or 'should probably see a rheumatologist' (15%). Fifteen per cent of referrals to orthopaedics were defined as 'could see either a surgeon or a rheumatologist'. Ninety-four per cent of referrals to rheumatology were defined as appropriate, 2% were not and 4% were defined as 'could see either a surgeon or a rheumatologist'. One year later, in a random sample of 373 of the orthopaedic referrals, 42.2% of those who were categorized as 'should see surgeon' and 9.7% of the 'should see a physician' group were listed for surgical intervention. CONCLUSIONS: Many referrals to hospital-based musculoskeletal services are likely to be misdirected. Integrated referral and care pathways are required for efficient and optimal care of patients with musculoskeletal diseases. The development of such pathways will require significant support, education and training for general practitioners.

Bone density in chronic low back pain: a pilot study.

BACKGROUND AND OBJECTIVE: Levels of physical activity in chronic low back pain patients are relatively low due to their fear of provoking pain. This may have a secondary impact on maintenance of bone mass. The objective of this study is to determine if patients with chronic low back pain are at a higher risk of bone demineralization. DESIGN: Bone mineral density (BMD) was measured in 25 chronic low back pain patients at the lumbar spine, hip and distal forearm. SETTING: A university hospital. SUBJECTS: Twenty-five chronic low back pain patients (mean age 45 years) enrolled on a residential back pain rehabilitation programme. RESULTS: Thirteen patients (52%) were osteopenic or osteoporotic in one or more sites. BMD at the lumbar spine was generally lower than the mean BMD of age-matched subjects (p = 0.04). There was no significant relationship between BMD and duration of pain, disability, sex or previous surgical intervention. CONCLUSIONS: Chronic low back pain patients have an increased incidence of osteopenia and osteoporosis. This finding reinforces the importance of motivating patients to incorporate exercise into daily life. Given the limited set of subjects used in the present study, further studies are required.

Anorexia nervosa and social class.

OBJECTIVES: (1) To examine social class status of female patients with anorexia nervosa presenting over a 33-year period; (2) to identify any differences in clinical features between the social classes. METHOD: Retrospective survey using comprehensive clinical database of patients referred to a national specialist center for the assessment and treatment of anorexia nervosa. Social class was defined using UK Registrar General's classification of father's occupation. Statistical methods included initial univariate analyses and subsequent ordinal logistic regression. RESULTS: (1) Social class distribution was consistently weighted toward social classes 1/2. (2) Possible clinical indicators examined included low body weight, binge eating, and consequent weight-regulatory behaviors such as vomiting and laxative and diuretic misuse. These clinical features and their distribution proved to be similar across the social groups. Clinically rated quality of family relationships and types of family constellations were also consistent across the social classes. (3) Dieting prodromata and onset of the disorder occurred at younger ages in social classes 1/2. (4) A modest shift in social class distribution over time was apparent, with slightly more patients presenting post-1985 likely to come from lower social classes. Claims that the social class distribution is a product of referral patterns and acceptances are disputed. CONCLUSION: We suggest that the social class bias reflects a sociocultural influence; a product of the disorder significantly often arising as an avoidant response to the conflict between social class-related family values/attitudes and adolescent turbulence within that family.

Is there a dissociative process in sleepwalking and night terrors?

The enduring and contentious hypothesis that sleepwalking and night terrors are symptomatic of a protective dissociative mechanism is examined. This is mobilised when intolerable impulses, feelings and memories escape, within sleep, the diminished control of mental defence mechanisms. They then erupt but in a limited motoric or affective form with restricted awareness and subsequent amnesia for the event. It has also been suggested that such processes are more likely when the patient has a history of major psychological trauma. In a group of 22 adult patients, referred to a tertiary sleep disorders service with possible sleepwalking/night terrors, diagnosis was confirmed both clinically and polysomnographically, and only six patients had a history of such trauma. More commonly these described sleepwalking/night terrors are associated with vivid dream-like experiences or behaviour related to flight from attack. Two such cases, suggestive of a dissociative process, are described in more detail. The results of this study are presented largely on account of the negative findings. Scores on the dissociation questionnaire (DIS-Q) were normal, although generally higher in the small "trauma" subgroup. These were similar to scores characterising individuals with post-traumatic stress disorder. This "trauma" group also scored particularly highly on the anxiety, phobic, and depression scales of the Crown-Crisp experiential index. In contrast the "no trauma" group scored more specifically highly on the anxiety scale, along with major trends to high depression and hysteria scale scores. Two cases are presented which illustrate exceptional occurrence of later onset of sleepwalking/night terrors with accompanying post-traumatic symptoms during wakefulness. It is concluded that a history of major psychological trauma exists in only a minority of adult patients presenting with sleepwalking/night terror syndrome. In this subgroup trauma appears to dictate the subsequent content of the attacks. However, the symptoms express themselves within the form of the sleepwalking/night terror syndrome rather than as rapid eye movement sleep related nightmares. The main group of subjects with the syndrome and with no history of major psychological trauma show no clinical or DIS-Q evidence of dissociation during wakefulness. The proposition that, within the character structure of this group, the mechanism still operates but exclusively within sleep remains a possibility.

A negative search for a paramyxoviral etiology of Paget's disease of bone: molecular, immunological, and ultrastructural studies in UK patients.

Paget's disease of bone is a common bone disease characterized by increased and disorganized bone remodeling at focal sites throughout the skeleton. The etiology of the disease is unresolved. A persistent viral infection has long been suggested to cause the disease. Antigen and/or nucleic acid sequences of paramyxoviruses (in particular measles virus [MV], canine distemper virus [CDV], and respiratory syncytial virus [RSV]) have been reported in pagetic bone by a number of groups; however, others have been unable to confirm this and so far no virus has been isolated from patients. Here, we reexamined the question of viral involvement in Paget's disease in a study involving 53 patients with established disease recruited from seven centers throughout the United Kingdom. Thirty-seven patients showed clear signs of active disease by bone scan and/or histological assessment of the bone biopsy specimens and 12 of these had not received any therapy before samples were taken. Presence of paramyxovirus nucleic acid sequences was sought in bone biopsy specimens, bone marrow, or peripheral blood mononuclear cells using reverse-transcription polymerase chain reaction (RT-PCR) with a total of 18 primer sets (7 of which were nested), including 10 primer sets (including 3 nested sets) specifically for MV or CDV. For each patient at least one sample was tested with all primer sets by RT-PCR and no evidence for the presence of paramyxovirus RNA was found in any patient. In 6 patients, bone biopsy specimens with clear histological evidence of active disease tested negative for presence of measles and CDV using immunocytochemistry (ICC) and in situ hybridization (ISH). Intranuclear inclusion bodies, similar to those described by others previously, were seen in pagetic osteoclasts. The pagetic inclusions were straight, smooth tubular structures packed tightly in parallel bundles and differed from nuclear inclusions, known to represent MV nucleocapsids, in a patient with subacute sclerosing panencephalitis (SSPE) in which undulating, diffuse structures were found, arranged loosely in a nonparallel fashion. In the absence of amplification of viral sequences from tissues that contain frequent nuclear inclusions and given that identical inclusions are found in other bone diseases with a proven genetic, rather than environmental, etiology, it is doubtful whether the inclusions in pagetic osteoclasts indeed represent viral nucleocapsids. Our findings in this large group of patients recruited from throughout the United Kingdom do not support a role for paramyxovirus in the etiology of Paget's disease.

Effect of early intervention with sumatriptan on migraine pain: retrospective analyses of data from three clinical trials.

OBJECTIVE: This study assessed the efficacy of sumatriptan 50- and 100-mg tablets in the treatment of migraine attacks while the pain is mild rather than moderate/severe. BACKGROUND: Results from The Spectrum Study suggested that early treatment of migraine attacks with sumatriptan 50-mg tablets while the pain is mild might enhance pain-free response and reduce headache recurrence. METHODS: Retrospective analyses of headaches treated during mild pain were performed using data from 3 studies of sumatriptan tablets (protocols S2CM09, S2BT25, and S2BT26). Our primary interest was pain-free response 2 and 4 hours after dosing; secondary interests were use of a second dose of medication, clinical disability (as measured on a 4-point disability scale), migraine-associated symptoms, meaningful pain relief (patient defined), time to meaningful relief, sustained pain-free response, and proportion of attacks in which pain had worsened 2 and 4 hours after dosing, all of which were compared in headaches treated during mild versus moderate/severe pain. RESULTS: In S2CM09, 92 patients treated 118 headaches during mild pain. Rates of pain-free response were higher 2 hours after dosing with sumatriptan 50 mg (51%) or 100 mg (67%; P < 0.05) compared with placebo (28%), and were higher with early treatment of mild pain compared with treatment of moderate/severe pain at 2 hours (sumatriptan 50 mg: mild pain, 51%; moderate/severe pain, 31%; P < 0.05; sumatriptan 100 mg: mild pain, 67%; moderate/severe pain, 36%) and 4 hours (50 mg: 75% vs 56%; 100 mg: 90% vs 61%; P < 0.05). Early intervention also resulted in less redosing than when moderate/severe pain was treated (50 mg: 21% vs 32%; 100 mg: 20% vs 29%). More attacks treated early with sumatriptan 50 or 100 mg were associated with normal function 4 hours after dosing compared with placebo (70% and 93% vs 46%, respectively). Sustained pain-free response rates 2 to 24 hours after early dosing with sumatriptan 50 or 100 mg were also higher (34% and 53%, respectively) compared with treatment of moderate/severe pain (19% and 24%, respectively). Early treatment with sumatriptan 100 mg produced significantly higher pain-free rates at 2 hours after dosing (P < 0.001) than did ergotamine plus caffeine (S2BT25: 69% vs 34%, respectively) or aspirin plus metoclopramide (S2BT26: 73% vs 25%, respectively). CONCLUSIONS: Sumatriptan 50- and 100-mg tablets are effective whether pain is mild or moderate/severe. However, treatment with sumatriptan while pain is mild provides high pain-free response rates while reducing the need for redosing, benefits not seen with ergotamine plus caffeine or aspirin plus metoclopramide.

Comparison of naratriptan and sumatriptan in recurrence-prone migraine patients. Naratriptan International Recurrence Study Group.

OBJECTIVE: This randomized, double-blind, crossover study was undertaken to compare the incidence of headache recurrence after treatment with naratriptan or sumatriptan in migraine patients with a history of frequent headache recurrence (recurrence in > or =50% of successfully treated attacks). BACKGROUND: Although the selective 5-hydroxytryptamine, (5-HT1) agonist sumatriptan is effective and well tolerated for acute treatment of migraine in most patients, headache recurrence within 24 hours of initial successful treatment with sumatriptan and other medications has been reported in approximately 35% of patients. The novel 5-HT1 agonist naratriptan possesses pharmacologic and pharmacokinetic characteristics that may address the issue of headache recurrence. METHODS: Men and women aged 18 to 65 years with a > or =1-year history of migraine with or without aura were randomly assigned to treat 1 moderate or severe migraine attack in a nonclinical setting with one 2.5-mg naratriptan tablet and 1 attack with one 100-mg sumatriptan tablet. A pain-free interval of > or =24 hours was required between attacks. At 4 hours, patients not using rescue medication and experiencing headache recurrence could take a second, identical dose of study medication to treat recurrence. No more than 2 tablets of study medication were permitted in any 24-hour period. RESULTS: A total of 253 patients treated > or =1 migrane attack and were included in the safety analysis; the 225 patients who treated both attacks were included in the efficacy analysis. Of the 164 naratriptan-treated and 181 sumatriptan-treated patients experiencing headache relief after > or =1 attack, headache recurrence 4 to 24 hours after treatment was reported by 74 naratriptan-treated patients (45%) and 101 sumatriptan-treated patients (57%; not statistically significant). (One naratriptan- and 3 sumatriptan-treated patients who experienced headache relief did not record recurrence status and were not included in the denominator for the percentage calculation.) In a subset of patients experiencing headache relief after 2 attacks, headache recurrence 4 to 24 hours after initial dosing was reported by 55 naratriptan- and 77 sumatriptan-treated patients (41% and 57%, respectively; P = 0.005). The overall incidence of adverse events was 22% after treatment with naratriptan and 33% after treatment with sumatriptan. This incidence did not increase after use of a second dose of naratriptan (20%) or sumatriptan (31%). CONCLUSION: These data suggest that naratriptan is a long-acting and well-tolerated addition to currently available medications for the treatment of acute migraine.