The proteomics of ageing

Proteomics provides an extremely powerful tool for the study of variations in protein expression between individuals, different disease states and different conditions. One of the major challenges facing the medical profession in the forthcoming decades is to understand the changes that occur in individuals as they become older and to attempt to develop means to improve the quality of life for the otherwise healthy ageing population. The present study describes the first phase of such an investigation in which the andaged protein composition of human skeletal muscle sample from young and aged subjects are compared. These results provide the beginning of a Human Aged Skeletal Muscle Profile reference map which is an essential first step to further investigations. This revised version was published online in July 2006 with corrections to the Cover Date.     

Alpha2 macroglobulin and the risk of Alzheimer's disease

BACKGROUND: alpha2 Macroglobulin is a panproteinase inhibitor that is found immunohistochemically in neuritic plaques, a requisite neuropathologic feature of AD. Recently, a pentanucleotide deletion near the 5' end of the "bait region" of the alpha2 macroglobulin (A2M) gene was reported to be associated with AD in a large cohort of sibpairs, in which the mutation conferred a similar odds ratio with AD as the APOE-epsilon4 allele for carriers of at least one copy of the A2M gene (Mantel-Haenszel odds ratio, 3.56). METHODS: We studied three independent association samples of AD patients (n = 309) with an age range of 50 to 94 years and representative controls (n = 281) to characterize the allele frequency of the pentanucleotide deletion in this cohort. We detected the mutation near the 5' splice site of exon 18 using standard PCR and restriction fragment length polymorphism methods. The results were adjusted for age, gender, education, and APOE polymorphism. RESULTS: We found that the A2M gene polymorphism conferred an increased risk for AD, with an estimated Mantel-Haenszel ratio of 1.5 (95% CI 1.1 to 2.2; p = 0.025). There was no age- or gender-dependent increase in A2M gene allele frequencies in AD patients compared with controls. The combined sample showed the expected association between AD and APOE-epsilon 4. In one of our three samples there was an interaction between the A2M and APOE-epsilon4 genes, but the other two samples showed no interaction between the two risk factors. CONCLUSIONS: Our data support an association between the A2M gene and AD. This association is less pronounced, however, in our cohort than in the previously reported sample of sibpairs.     

The operative management of displaced intra-articular fractures of the calcaneum: a two-centre study using a defined protocol

The management of intra-articular calcaneal fractures remains controversial with strong arguments supporting both conservative and operative management. This study assesses the results of open reduction and internal fixation (ORIF) of displaced intra-articular fractures of the calcaneum in two independent centres where the indications for operative management had been strictly defined.Forty-seven patients (51 fractures) who had sustained such injuries underwent an ORIF performed by one of the senior surgeons using the technique described by Eastwood et al. [JBJS 75-B(1993)189] All of the fractures were assessed by plain X-ray and CT scan and graded according to the Sanders classification [Clin. Orthop. 290(1993)97]. Patients were assessed at a minimum of 2 years post-surgery both clinically and with a standardised questionnaire based on that described by Kerr et al. [Injury 27(1996)35].The mean age at operation was 42 and 50 years for the two centres, and the mean follow-up was 44 months. Seventy-six per cent of the patients were male. Eighty-eight per cent of the injuries were due to a fall from a height. Fifteen patients had contralateral foot/ankle injuries. Thirty-four of 46 patients were in employment at the time of the injury, 24 of these were in physical jobs and 20 sustained their injury whilst at work.Overall, the satisfaction rate was 90%. Ninety-four per cent of patients in work returned to work at a median of 6 months. Bilateral injuries were associated with a significantly poorer outcome as were those with heel pad pain. Delay to operation greater than 14 days was associated with a higher infection rate. Smoking was not related to infection rate.     

The national cot death prevention program in New Zealand

Abstract: A case-control study examining the risk factors for sudden infant death syndrome (SIDS) in New Zealand identified three risk factors that are potentially amenable to modification: prone sleeping position of the infant, maternal smoking and lack of breastfeeding. In total these three risk factors may account for 79 per cent of deaths from SIDS in New Zealand. We describe the planning and implementation of the cot death prevention program, which has involved a wide range of groups and different strategies. The outcome of the prevention program is being evaluated.     

Estimates of the prevalence of bipolar affective disorder METHODS BASED ON TREATMENT WITH LITHIUM

During this century the epidemiology of the affective disorders has been studied, several classifications have been described and effective treatment measures have been introduced. Difficulties have been encountered in the epidemiology area due to inconsistent use of the terminology of measurement and varying types of classification; although it is possible to arrive at a broad consensus of agreement if the data are examined restrictedly. The clinical need for accurate rates of illness has become greater since the inception of the prophylactic drug lithium carbonate. While not used specifically for bipolar affective disorder, it is only for this disorder that its use has been demonstrated beyond doubt. The occurrence of mania in this disorder enables this aspect of the condition to be used as a marker. This paper describes three measures of the period prevalence of bipolar affective disorder, based upon treatment with lithium, two of which are of the ‘unobtrusive’ type. Agreement was found between the three approaches and the utility of these for general use is discussed.