ACTN3 genotypes of Rugby Union players: distribution, power output and body composition.

BACKGROUND AND AIM: To identify the distribution and explore the relationship between ACTN3 genotypes and power and body composition phenotypes. SUBJECTS AND METHODS: Case control and association studies were employed using a homogeneous group of players (n = 102) and a control group (n = 110). Power-related phenotypes were measured using the counter movement jump (CMJ) and body composition phenotypes by dual-energy X-ray absorptiometry (DXA). Statistics used were Pearson's chi-square, ANCOVA, coefficients of correlation and independent t-tests. Genotyping was carried out using polymerase chain reaction followed by enzymatic Ddel digestion. RESULTS: Genotype proportions of players were compared with controls (p = 0.07). No significant genotype differences occurred between forwards or backs (p = 0.822) or within-forwards (p = 0.882) or within-backs (p = 0.07). Relative force and velocity were significantly larger in backs, power significantly greater in forwards; in body composition, all phenotypes were significantly greater in forwards than backs. Correlations between phenotypes were greater for the RX genotype (p = 0.05-0.01). CONCLUSIONS: Relationships between ACTN3 genotypes and power or body composition-related phenotypes were not significant. As fat increased, power-related phenotypes decreased. As body composition increased, power-related phenotypes increased.

ACE ID genotype and leg power in Rugby Union players.

AIM: The present study examined the hypothesis that there were no significant differences between forwards and backs in the elements of leg power between the ID and DD genotypes of the ACE (I/D) gene in developing young adult Rugby Union players. METHODS: Sixty-eight players were recruited to identify the distribution of genotypes between forwards and backs. Fifty-eight players were investigated for leg power. Forwards (n=28) comprised 15 ID and 13 DD genotypes, and backs (n=30) 19 ID and 11 DD genotypes. Leg power was measured on a force platform using a counter movement jump; the parameters of interest were peak and relative force, peak and relative power, displacement and velocity. The three-primer polymerase chain reaction was used to assay the region of interest for I and D variants of the ACE gene. The distribution of genotypes was determined by chi-square and comparisons between forwards and backs made using the independent t-test. RESULTS: No significant differences were identified in the distribution of genotypes between forwards and backs (χ2=2.2, P=0.336). However, significant differences were identified between forwards and backs in a number of components of leg power. Backs had significantly larger values than forwards for relative force (1.50 vs. 1.30 Wt%, P=0.001) and relative power (27.1 vs. 24.3 W.kg-1, P=0.034) for the ID genotype, whereas backs had significantly larger values than forwards for displacement (0.42 vs. 0.38 m, P=0.049) and velocity (2.76 vs. 2.55 m.s.(-1), P=0.007) for the DD genotype. CONCLUSION: The characteristics of leg power identified will enhance the functional requirements of players according to playing position and commitment.

Inherited predisposition to colorectal adenomas caused by multiple rare alleles of MUTYH but not OGG1, NUDT1, NTH1 or NEIL 1, 2 or 3.

BACKGROUND: MUTYH-associated polyposis (MAP) is a recessive trait characterised by multiple colorectal adenomas and a high risk of colorectal cancer. MUTYH functions in the DNA base excision repair pathway and has a key role in the repair of oxidative DNA damage. OBJECTIVES: To assess the contribution of inherited variants in genes involved in base excision repair and oxidative DNA damage including MUTYH, OGG1, NEIL1, NEIL2, NEIL3, NUDT1 and NTH1 to the multiple colorectal adenoma phenotype. METHODS: Inherited variants of MUTYH, OGG1, NEIL1, NEIL2, NEIL3, NUDT1 and NTH1 were sought in 167 unrelated patients with multiple colorectal adenomas whose family histories were consistent with recessive inheritance. These variants were also characterised in approximately 300 population controls. RESULTS: Thirty-three patients (20%) and no controls were MUTYH homozygotes or compound heterozygotes (ie, carried two mutations) and therefore had MAP. Eight different pathogenic MUTYH mutations were identified, of which four were novel. MAP cases had significantly more adenomas than non-MAP cases (p = 0.0009; exact test for trends in proportions) and presented earlier (p = 0.013; analysis of variance). Twenty-four protein-altering variants were identified upon screening of OGG1, NEIL1, NEIL2, NEIL3, NUDT1 and NTH1. However, all combinations of two (or more) variants that were identified at an individual locus in patients were also seen in controls, and no variants were significantly over-represented (or under-represented) in cases. CONCLUSION: Multiple rare alleles of MUTYH are associated with autosomal recessive MAP, while OGG1, NEIL1, NEIL2, NEIL3, NUDT1 and NTH1 do not contribute significantly to autosomal recessive polyposis.

Teaching stress management in undergraduate dental education: are we doing enough?

Dentistry is recognised as a stressful profession. A number of studies focusing on undergraduate education have shown high levels of stress in dental students. However, despite calls to do so, little has been published on methods to teach future dental professionals about stress and how to manage it on a personal level. Psychological stress which is uncontrolled may have an effect on general health. It is recognised, however, that stress can be beneficial if channelled appropriately. Techniques and ways to teach management of potential stresses of a career in dentistry have still not been widely reported in either dental undergraduate or postgraduate education. An intervention used with final year dental students at the University of Portsmouth for the last four years has highlighted some of the problems raised by students coping with a stressful programme of study. Students' comments indicated the need for an educational intervention on recognising and reducing stress to be introduced earlier on in their curriculum and that it should be universally taught.

CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients.

OBJECTIVE: To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. METHODS: Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. RESULTS: Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett-like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto-temporal predominance and high amplitudes. CONCLUSIONS: The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder, irrespective of whether they have suspected Rett syndrome. Analysis should be considered in these patients in the clinical setting.

Simplified analysis of pathogenic leptospiral serovars by random amplified polymorphic DNA fingerprinting.

A rapid, simplified procedure combining random amplified polymorphic DNA (RAPD) fingerprinting of boiled cultures with high resolution agarose gel electrophoresis was used to compare strains from 46 pathogenic leptospiral serovars. The serovars were placed in eight groups on the basis of RAPD profile similarities. Groups 1-7 corresponded with the genome species Leptospira interrogans, L. borgpetersenii, L. santarosai, L. noguchii, L. weilii, L. kirschneri and L. meyeri. The eighth group did not correspond with a known genome species and may represent a new genome species. Primer choice determined the degree of discrimination possible between closely related serovars and genotypes. This procedure, unlike other procedures used for analysing taxonomic relationships between leptospiral serovars, does not require extensive DNA purification, polyacrylamide gel electrophoresis or autoradiography.

Accumulation of factors influencing respiratory illness in members of a national birth cohort and their offspring.

STUDY OBJECTIVE: The aim was to investigate predictors of childhood lower respiratory tract illness in two generations, and predictors of adult lower respiratory disorders in the first generation. DESIGN: Data on respiratory health and environmental factors from a national birth cohort study were examined from birth to 36 years. Data were also collected on the parents of the subjects and on the subjects' first born offspring from birth to eight years. Main outcome measures were: reports of lower respiratory tract illness before 2 years; lower respiratory tract illness of a week or more between age 20 and 36 years; regular phlegm production at 25 and 36 years; reports of wheeze or asthma at age 36 years; peak expiratory flow rate (PEFR) at age 36 years measured by nurses during home visits; and mothers' reports of lower respiratory illness in first born offspring before 2 years. SUBJECTS: Subjects were a sample of 5362 single, legitimate births taken from all those occurring in England, Wales, and Scotland in one week in 1946, and studied regularly from birth to age 43 years. Data on the subjects' parents and on their 1676 first offspring born while they were aged 19-25 years were also collected. MAIN RESULTS: Lower respiratory tract illness before 2 years fell from 25% in the population born in 1946 to 13% in their first born offspring. In those born in 1946, poor home environment, parental bronchitis, and atmospheric pollution were the best predictors of lower respiratory illness before 2 years, and these three factors and childhood lower respiratory illness and later smoking were the best predictors of adult lower respiratory tract problems. Risk factors for lower respiratory illness in the offspring were manual social class, parental and grandparental lower respiratory disease, and parental smoking. CONCLUSIONS: Risks for adult lower respiratory problems accumulated in childhood through illness, poor social circumstances, and atmospheric pollution. Smoking exacerbated early life risks and was an independent risk factor. In the offspring generation, parental smoking was a risk factor for early life chest illness, together with parental illness and low social class. Reduction of prevalence in the offspring generation was probably accounted for by improvement in home circumstances, reduced atmospheric pollution, and lower rates of parental lower respiratory illness, but current rates of smoking seem likely to prevent much further reduction in early life lower respiratory illness, and thus in this aspect of risk for subsequent adult lower respiratory problems. The accumulation of risk in childhood and adolescence for later adult problems implies a long time scale for the reduction of adult lower respiratory disorders.

Respiratory effects of lowering tar and nicotine levels of cigarettes smoked by young male middle tar smokers. I. Design of a randomised controlled trial.

STUDY OBJECTIVE: The aim was to investigate the effect on respiratory health of male middle tar smokers changing the tar and nicotine levels of the cigarettes they smoke for a six month period. DESIGN: This was a randomised controlled trial. Middle tar smokers were randomly allocated to smoke one of three different types of cigarette (low tar, middle nicotine; middle tar, middle nicotine; and low tar, low nicotine) in place of their usual cigarette for a six month period. Main outcome measures were assessment of respiratory health by documenting respiratory symptoms and peak expiratory flow rates, and of nicotine inhalation by measuring the urinary excretion of nicotine metabolites. SETTING: 21 local authority districts of England. SUBJECTS: Participants were male middle tar smokers aged 18-44 years. MAIN RESULTS: Postal questionnaires were sent to 265,016 individuals selected from the electoral registers of 21 local authority districts of England; 64% of questionnaires were returned revealing 7736 men aged 18-44 years who smoked only middle tar cigarettes. Of these, 7029 (90%) were sent a health warning and 707 (10%) were not; the latter acted as a control group to assess the effect of the health warning. Of the 7029 men who had received a health warning and were visited at the recruitment stage, 2666 agreed and were eligible to participate in the trial although only 1541 (58% of those who agreed and were eligible) actually started smoking the study cigarettes; 643 men (24% of those willing to participate at the beginning of the trial and 42% of those who actually started smoking the study cigarettes) completed the trial smoking the study cigarettes. Of these, 213 were in the low tar middle nicotine group, 220 were in the middle tar middle nicotine group, and 210 were in the low tar low nicotine group. CONCLUSIONS: This study shows the feasibility of identifying and recruiting sufficient numbers of male middle tar smokers, with adequate numbers completing the trial, to detect any changes in respiratory health over a six month period.

Respiratory effects of lowering tar and nicotine levels of cigarettes smoked by young male middle tar smokers. II. Results of a randomised controlled trial.

STUDY OBJECTIVE: The aim was to investigate the effect on respiratory health of male middle tar smokers changing the tar and nicotine levels of the cigarettes they smoke for a six month period. DESIGN: This was a randomised controlled trial. Middle tar smokers were randomly allocated to smoke one of three different types of cigarette (low tar, middle nicotine; middle tar, middle nicotine; and low tar, low nicotine) in place of their usual cigarette for a six month period. Main outcome measures were assessment of respiratory health by documenting respiratory symptoms and peak expiratory flow rates, and of nicotine inhalation by measuring the urinary excretion of nicotine metabolites. SETTING: 21 local authority districts of England. SUBJECTS: Participants were male middle tar smokers aged 18-44 years. MAIN RESULTS: Changes in the measures of respiratory health showed little difference over the trial period between the three cigarette groups. Analyses of the urinary nicotine metabolites showed that smokers allocated to each of the three study cigarettes adjusted their smoking so that throughout the trial their nicotine inhalation differed little from their pretrial intakes when they were smoking their own cigarettes. As a result of the altered patterns of smoking to compensate for the reduced nicotine yields of the three study cigarettes, the tar intake of those allocated to smoke the middle tar, middle nicotine cigarettes remained essentially unchanged, while those allocated to smoke the low tar, low nicotine and low tar, middle nicotine cigarettes had calculated reductions in tar intakes of about 14% and 18%, respectively. CONCLUSIONS: Due to the phenomenon of compensation, tar intake can only be reduced substantially by using a cigarette with a markedly lower tar/nicotine ratio. Nevertheless reductions of up to about 18% in tar intake failed to result in any detectable effect on respiratory symptoms or peak expiratory flow rates over a six month period.

The oral toxicity of 1-amino-3-chloro-propanol hydrochloride (CL 88236) in rats.

1-amino-3-chloro-2-propanol (CL 88236) was administered by oral gavage for 12 consecutive weeks to rats at dose levels of 50, 250 and 500 mg/kg/day. All levels gave rise to toxicological effects. Epididymal necrosis and/or atrophy of the seminiferous epithelium was found for some males with each dose of CL 88236. The kidney and liver weights of male and female rats given CL 88236 were higher than control values but no histological changes were found in these organs.

Toxicity studies with quinine hydrochloride.

Three-month studies in the rat, a rat embryo-toxicity study and a specific study to investigate ototoxicity were carried out with quinine hydrochloride. The results of these studies suggest an acceptable daily intake of 40 mg quinine hydrochloride for an adult. There were no indications of teratogenic effects and no indications of interference with auditory function in rats receiving up to 200 mg/kg.

Rapid confirmatory identification of Mycobacterium bovis using a dot blotting immunodetection technique.

A safe, cost effective and accurate immunodetection technique for the rapid identification of Mycobacterium bovis colonies is described. One hundred and thirteen M. bovis isolates were differentiated from other species of mycobacteria using a M. bovis specific monoclonal antibody, with nitrocellulose membrane as the solid support. The technique confirms M. bovis identification in only 4 h compared to 3 weeks for conventional antibiotic sensitivity tests.

Fetal lipoproteins and placental release of esterified lipids.

An in vitro incubation technique was used to examine the release of lipids from the rabbit placenta. Free fatty acid, but not phospholipid or triacylglycerol, was released into the incubation media. In a second series of experiments, the addition of lipids to the umbilical circulation was studied in situ in the placenta of anaesthetized rabbits at late gestation. Each placenta was perfused from the fetal side in turn with two different perfusate solutions, either 4% bovine albumin solution or rabbit plasma. The rabbit plasma contained the appropriate carriers (lipoproteins) for esterified lipids, whereas the 4% albumin solution did not. The effluent perfusates were remarkably similar in free fatty acid concentration and composition, which closely matched the maternal free fatty acid profiles. The concentrations and fatty acid composition of the perfusate triacylglycerol and phospholipid fractions were unchanged by passage through the placenta, whether perfused with 4% albumin or with rabbit plasma. With this system, no evidence could be found for the addition of esterified lipids to the umbilical circulation in the rabbit despite the provision of appropriate carriers on the fetal side of the placenta.

Dental effects of xylitol compared with other carbohydrates and polyols in the diet of laboratory rats.

Xylitol at 10 and 20 per cent disturbed gastro-intestinal function but was tolerated better than sorbitol or mannitol. Toleration improved when dietary polyol levels were increased gradually to a maximum of 20 per cent. Twenty per cent of xylitol in the diet replacing that amount of sucrose reduced the level of caries, but 20 per cent of wheat starch was equally effective. Ten per cent of xylitol in place of sucrose produced as much caries as the basic cariogenic diet, but xylitol at a level of 2 per cent was associated with an increase in caries. There was no confirmation of an active caries-reversing effect of xylitol when xylitol-containing diets were alternated with the basic high-sucrose cariogenic ration.

Prosthetic valve endocarditis developing after an infected scalp laceration.

This case report describes a 21-year-old man who developed prosthetic valve endocarditis (PVE) from an infected scalp laceration. Despite intravenous antibiotic therapy, the infectious process could not be controlled and the patient required replacement of the aortic valve. Our patient is the fourth case of late PVE occurring after a subcutaneous infection. In each case, antibiotic prophylaxis of infective endocarditis was not practiced. Current antibiotic regimens for prophylaxis of PVE are reviewed.

Compartment syndrome. A dorsal pedal presentation.

Compartment syndrome presents an emergency situation to the surgeon. Inordinate delay in performing a fasciotomy poses potential loss of limb or irreversible neuromuscular damage. Recognizing those injuries that may cause a compartment syndrome and careful monitoring of the at-risk patient during the early post-traumatic period are mandatory.