Search

Background: Small birth size may be associated with increased risk of cardiovascular diseases (CVD), whereas large birth size may predict increased risk of obesity and some cancers. The net effect of birth size on long-term mortality has only been assessed in individual studies, with conflicting results., Methods: The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines for conducting and reporting meta-analysis of observational studies were followed. We retrieved 22 studies that assessed the association between birthweight and adult mortality from all causes, CVD or cancer. The studies were systematically reviewed and those reporting hazard ratios (HRs) and 95% confidence intervals (95% CIs) per kilogram (kg) increase in birthweight were included in generic inverse variance meta-analyses., Results: For all-cause mortality, 36,834 deaths were included and the results showed a 6% lower risk (adjusted HR = 0.94, 95% CI: 0.92-0.97) per kg higher birthweight for men and women combined. For cardiovascular mortality, the corresponding inverse association was stronger (HR = 0.88, 95% CI: 0.85-0.91). For cancer mortality, HR per kg higher birthweight was 1.13 (95% CI: 1.07-1.19) for men and 1.04 (95% CI: 0.98-1.10) for women (P(interaction) = 0.03). Residual confounding could not be eliminated, but is unlikely to account for the main findings., Conclusion: These results show an inverse but moderate association of birthweight with adult mortality from all-causes and a stronger inverse association with cardiovascular mortality. For men, higher birthweight was strongly associated with increased risk of cancer deaths. The findings suggest that birthweight can be a useful indicator of processes that influence long-term health.

Background: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background., Objective: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight., Design: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (n(max) = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (n(max) = 10,623); and 3) all published data (n(max) = 14,837)., Results: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing., Conclusions: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.

Background: recent studies suggest that diet may affect the physical performance of older adults, but the impact of variations in the UK diet on physical performance has not been assessed., Objective: to examine relationships between diet and physical performance in community-dwelling older men and women., Setting and Participants: a total of 628 men and women aged 63-73 years who were taking part in the Hertfordshire Cohort Study., Methods: diet was assessed using an administered food frequency questionnaire; physical performance was assessed by the time taken to complete a 3-m walk, chair-rise test and one-legged balance test., Results: in women, higher intakes of the antioxidant nutrients, β-carotene and selenium, were associated with shorter 3-m walk times; higher β-carotene and vitamin C intakes were associated with shorter chair-rise times (all P < 0.05). Higher vitamin D intakes and percentage energy from protein were also associated with faster 3-m walk times (both P < 0.05), but they were not related to chair-rise time. There were no associations between any measure of dietary intake and balance in the women studied. After adjustment for the effects of confounding influences, we found no associations between diet and physical performance among men., Conclusions: these data indicate that variations in the diets of community-dwelling older women may be linked to differences in physical performance, but further work is needed to determine the role of variations in diet on physical performance and its decline with age among older adults in the UK.

Summary: This study of 22 girls with Turner syndrome (TS) demonstrates a reduction in bone mineral apparent density (BMAD) at the femoral neck along with a reduction in cortical bone density at the radius (with sparing of trabecular bone). These findings may account for the increased fracture risk noted in this population., Introduction: Increased fracture risk is a feature of TS; however, the reasons for this are unclear. Little is known regarding cortical and trabecular bone mineral density (BMD) in TS. We have addressed this by measurement of volumetric bone mineral density (vBMD) using peripheral quantitative computed tomography (pQCT)., Methods: We studied 22 females with TS and 21 females without TS; mean ages 12.7 and 12.9 years, respectively. Bone mass measurements were made by dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femur and pQCT of the radius. BMAD was calculated from DXA values. We utilized published reference data to generate Z-scores for both populations., Results: The mean BMAD Z-score at the lumbar spine was not significantly different in individuals with TS compared to the controls. At the femoral neck, individuals with TS had a significantly lower BMAD Z-score compared to the controls (-1.32 vs. -0.14, p = 0.001). At the distal radius, total vBMD Z-score and trabecular vBMD Z-score were not significantly different between the TS group and controls. A significant reduction in cortical vBMD at the proximal radius was noted in the TS group however (-2.58 vs. -1.38, p = 0.02). There was also a trend towards reduced cortical thickness at this site in the TS group (Z-score -2.89 vs. -1.73, p = 0.08)., Discussion: TS is associated with reduced BMAD at the femoral neck; pQCT data suggests that cortical density is reduced with sparing of trabecular bone. This differential of cortical and trabecular BMD may predispose to fracture.

Introduction: Wrist fracture causes pain and decreased physical, social and emotional function. The International Osteoporosis Foundation has developed a specific questionnaire to assess quality of life in patients with wrist fracture. This questionnaire, including 12 questions, was validated in a multicentre study and compared with an osteoporosis-specific questionnaire (Qualeffo-41) and a generic questionnaire (EQ-5D)., Methods: The study included 105 patients with a recent wrist fracture and 74 sex- and age-matched control subjects. The questionnaire was administered as soon as possible after the fracture, at 6 weeks, 3 months, 6 months and 1 year after the fracture. Test-retest reproducibility, internal consistency and sensitivity to change were assessed., Results and Discussion: The results showed adequate repeatability and internal consistency of the International Osteoporosis Foundation (IOF) wrist fracture questionnaire. The discriminatory capacity between patients and control subjects was very high, with significant odds ratios for each question and domain. The IOF-wrist fracture questionnaire domain scores showed significant improvement after 3 and 6 months and some improvement from 6 months up to 1 year. The sensitivity to change was much higher for the IOF-wrist fracture total score than for Qualeffo-41 and EQ-5D., Conclusion: In conclusion, the IOF-wrist fracture questionnaire appears to be a reliable and responsive quality of life questionnaire.

Background: dietary patterns analysis takes account of the combined effects of foods and may be a more meaningful way of assessing dietary exposure than considering individual nutrients. Little is known about the dietary patterns of older adults in the UK., Objective: to describe the dietary patterns of a population of community-dwelling older men and women and to examine factors associated with compliance with these patterns., Setting and Participants: 3,217 men and women aged 59-73 years who were participants in the Hertfordshire Cohort Study., Methods: diet was assessed using an administered food frequency questionnaire; dietary patterns were identified using principal component analysis., Results: two dietary patterns were identified. The first was characterised by high consumption of fruit, vegetables, oily fish and wholemeal cereals ('prudent' pattern); the second was characterised by high consumption of vegetables, processed and red meat, fish and puddings ('traditional' pattern). High 'prudent' diet scores were more common in women, in men and women in non-manual classes and in non-smokers (all P < 0.05), whilst high 'traditional' diet scores were more common in men, in men and women who had partners and were associated with higher alcohol consumption (all P < 0.05)., Conclusions: we have described large variations in food consumption and nutrient intake amongst older adults that are likely to have implications for future health. The specific socio-demographic correlates of the dietary patterns provide insights into the contexts within which good and poor diets exist, and may help in the identification of opportunities for dietary intervention.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity., Competing Interests: The authors from Decode Genetics Inc. own stocks and stock options in the company. VM, NL, KS and DMW are full-time employees of GlaxoSmithKline, a pharmaceutical company. The other authors have no competing interests to declare.

Background: UK consensus guidelines recommend limited use of self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes using diet and exercise, metformin and/or a glitazone. This analysis quantifies the usage of and costs associated with SMBG in type 2 diabetes according to treatment regimen., Methods: Prevalence data for diabetes were assessed using UK Quality and Outcomes Framework returns for 2006/2007. Data on current SMBG prescribing expenditure were extracted from UK Prescription Pricing Agency Data for 2007. Prescribing data were extracted from the records of 40,651 patients with diabetes on the IMS Disease Analyzer (MediPlus) database. These were combined to arrive at mean usage and expenditure data per patient, broken down by treatment type. The analysis assumes that it is appropriate to use patients' treatment regimen alone to compare the frequency of SMBG in clinical practice with the frequency recommended in treatment guidelines; it does not take into account other valid reasons for SMBG., Results: Mean national expenditure on SMBG was 73.64 pound sterling per patient per year. Estimated mean weekly test strip usage by treatment was 2.5 (diet), 2.6 (glitazone monotherapy), 3.1 (metformin monotherapy) and 3.5 (sulphonylurea monotherapy). Combination oral therapy ranged from 3.3 to 4.1. Mean annual expenditure in patients with an identified treatment type was 62.06 pound sterling per patient, ranging from 9.83 pound sterling for diet-treated patients to 37.87 pound sterling for those on triple therapy, with insulin-treated patients incurring costs 3-5 times higher., Conclusions: Based on the assumptions that the treatment regimen is the sole factor in determining the appropriate level of SMBG frequency, this study demonstrates that the use of SMBG exceeds current guidelines in certain treatment groups. The study estimates that the potential savings of up to 17 million pound sterling could be made each year if guidelines were followed more closely. There is a need for further research into SMBG use in patients with type 2 diabetes.

Objectives: Radiographic osteoarthritis (ROA) has previously been shown to be associated with an increase in areal bone mineral density (BMD) as assessed by dual energy X-ray absorptiometry (DXA). Here we have assessed volumetric bone density, size and strength by peripheral quantitative computed tomography (pQCT) in a large population-based cohort study in which knee radiographs were available., Methods: Two hundred and ninety-five men and 288 women from the MRC Hertfordshire Cohort Study underwent weight bearing extended knee X-rays and bone density measurement of the ipsi-lateral knee using pQCT., Results: Increasing radiographic grade in men but not women was associated with an increase in tibial total area at 38% site and cortical area at 14% site, but not with volumetric BMD. The tibial fracture loads as well as tibial polar strength strain index at 38% site were also increased. There were no significant associations of tibia bone area, BMD or strength with radiographic grade in women., Conclusion: ROA is not associated with an increase in volumetric BMD as assessed by pQCT. It is, however, associated with a significant increase in bone area and strength, indicating that the association between ROA and areal BMD is mediated through bone size rather than volumetric BMD.

This study measured the effect of a 20-week, family-centered electronic media intervention on electronic media use, body composition (dual-energy X-ray absorptiometry; DXA), physical activity and dietary behaviors in boys. Twenty-two boys were assigned and 21 were analyzed in an experimental or control group. Boys in the experimental group set electronic media use goals and used TV Allowance device and ENUFF software to reduce electronic media use. Data were collected at baseline, 10 weeks and 20 weeks. Interactions were found in daily electronic media use and DXA. At 10 weeks, step counts increased by 543 steps per day in the experimental group and decreased by 340 steps per day in the controls. Steps in both groups were higher at 20 weeks. Meals or snacks eaten while using electronic media decreased in the experimental group only. In conclusion, a family-centered electronic media intervention may reduce electronic media use and contribute to desirable changes in body composition.

Objective: The objective of this study is to describe current self-monitoring of blood glucose (SMBG) practice for patients with type 2 diabetes by treatment type and adherence with healthcare professional advice concerning SMBG. In addition, the study aims to investigate the association of SMBG and self-reported episodes of low blood glucose., Design and Setting: This cross-sectional survey design study was carried out on patients with type 2 diabetes aged 18 years or over, attending community pharmacies in 97 sites across the United Kingdom., Methods: Patients picking up a prescription for blood glucose test strips or diabetes medicine from a community pharmacist were asked to complete a questionnaire. The pharmacist was available to assist if requested. Questions included: self-reports of frequency of blood glucose testing; type of diabetes treatment; advice given by healthcare professionals about frequency of blood glucose testing; frequency of episodes of low blood glucose; and last known HbA(1c) level. The final sample size was 554 respondents, who were grouped for analysis as follows: those being treated with insulin, either alone or with any oral medication (n = 167); those being treated with sulfonylureas, either alone or with any oral medication (n = 187); and those being treated with any other medication, or controlled by diet and exercise alone (n = 202)., Results: Frequency of SMBG was higher in patients using insulin (median 10 times per week, Q (1), Q (3) = 4.5, 14) than in patients on treatments other than insulin (four times per week, Q (1), Q (3) = 2, 7, p < 0.001). SMBG was carried out at the same frequency in patients not treated with insulin regardless of whether they were prescribed sulfonylureas. Greater frequency of SMBG was associated with self-reports of one or more episodes of low blood glucose in the previous six months., Conclusions: Among patients with type 2 diabetes, those treated with insulin used SMBG at a greater frequency than those not treated with insulin. Increased frequency of testing was associated with increased frequency of self-reported episodes of low blood glucose, even among patients not taking insulin or sulfonylureas. This raises the possibility that episodes of hypoglycaemia may not be accurately identified, leading to unnecessary fear, or conversely that treatment is not being adjusted to avoid such morbidity. Although further work is needed to explore this association in a representative, prospective cohort of patients, possible explanations for reports of low-blood glucose should be discussed with patients using SMBG more frequently to ensure they are able to accurately identify episodes of hypoglycaemia.

Background: A number of studies have shown strong graded positive relationships between size at birth, grip strength, and estimates of muscle mass in older people. However no studies to date have included direct measures of muscle size., Methods: We studied 313 men and 318 women born in Hertfordshire, United Kingdom between 1931 and 1939 who were still resident there and had historical records of growth in early life. Information on lifestyle was collected, and participants underwent peripheral quantitative computed tomography to directly measure forearm and calf muscle size., Results: Birth weight was positively related to forearm muscle area in the men (r = 0.24, p <.0001) and women (r = 0.17, p =.003). There were similar but weaker associations between birth weight and calf muscle area in the men (r = 0.13, p =.03) and in the women (r = 0.17, p =.004). These relationships were all attenuated by adjustment for adult size., Conclusion: We present first evidence that directly measured muscle size in older men and women is associated with size at birth. This may reflect tracking of muscle size and is important because it suggests that benefit may be gained from taking a life course approach both to understanding the etiology of sarcopenia and to developing effective interventions.

Objective: Sitagliptin is a novel oral incretin enhancer that acts by inhibiting the dipeptidyl peptidase 4 enzyme and is indicated in Europe as a treatment adjunct to metformin (MF), sulphonylurea (SU), MF plus SU and diet and exercise, in the management of type 2 diabetes mellitus. The objective of the current analysis was to evaluate the cost-effectiveness of adding sitagliptin to the regimens of patients with haemoglobin A1c (HbA1C) above the International Diabetes Federation goal (6.5%) while on MF in six European countries: Austria, Finland, Portugal, Scotland (United Kingdom), Spain and Sweden., Methods: A discrete event simulation model, which employed the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model risk equations for predicting risks of diabetes-related complication, was used. Lifetime costs and benefits were projected for alternative treatment strategies of adding sitagliptin, compared with adding rosiglitazone or a SU to MF in patients not at HbA1C goal on MF monotherapy. Changes in HbA1C as well as side effects associated with these different treatment strategies were based on clinical trial data. Mean baseline values from local epidemiologic studies involving patients with type 2 diabetes not at HbA1C goal on MF monotherapy were included in the current analysis. Costs of medications, side effects and direct costs of diabetes-related complications were based on country-specific data. UKPDS-based disutility weights associated with diabetes complications were incorporated. Disutilities associated with medication side effects were based on published data. All future costs and benefits were discounted according to local guidelines on cost-effectiveness analysis. One-way sensitivity analyses were conducted by varying key input parameters., Findings: The discounted incremental cost-effectiveness ratios (ICER) associated with the addition of sitagliptin to MF, compared with adding rosiglitazone, in the different countries analysed ranged from treatment with sitagliptin being dominant (cost saving with improved health outcome) to its being cost-effective [4,766 euros per quality-adjusted life year (QALY)]. Treatment with sitagliptin added to MF was cost-effective compared with adding a SU, with discounted ICER values ranging from 5949 euros/QALY to 20,350 euros/QALY across countries. Sensitivity analyses showed that these results were robust to changes in input parameters, including clinical efficacy, costs and utility weights for both diabetes-related complications and hypoglycaemia., Conclusions: Compared with adding rosiglitazone or a SU to MF, adding sitagliptin to MF is projected to be either cost saving or cost-effective for patients with type 2 diabetes who are not at HbA1C goal on MF.

The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication-in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self-reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes-both direct hospital costs and indirect costs-are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around pound1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications.

Objectives: There has been limited success defining environmental factors important in the development of antiphospholipid (Hughes) syndrome (APS). Recent work suggests that the perinatal environment may be important in the development of other autoimmune diseases. We measured anticardiolipin antibodies (aCL) in a general population with well-defined early lives to see whether fetal and infant growth and infections were associated with aCL positivity in adult life., Methods: aCLs were measured using an ELISA in 1384 individuals from the Hertfordshire cohort study. We investigated associations between the presence of aCL and early growth and infectious exposure in infancy in men and women., Results: ELISA positive aCL (IgM and IgG) was present in 22 (3%) men and 15 (2%) women. Using the highest octile of aCL results, in men higher birth weight (per lb of birth weight: OR 1.18, 95% CI 1.02-1.36, P = 0.02) and diarrhoeal infection in the first year of life (OR 2.55, 95% CI 1.10, 5.92, P = 0.03) were associated with an increased likelihood of being aCL positive. In women, diarrhoeal infection in the first year of life was also associated with an increased likelihood of aCL positivity (OR 2.23, 95% CI 1.01, 4.91, P = 0.05). For IgG titre in men, significant relationships were found with sharing a bedroom (regression coefficient 1.13; 95% CI 1.05, 1.22; P = 0.02) and diarrhoea in the first year (coefficient 1.25; 95% CI 1.00, 1.56; P = 0.05)., Conclusion: A developing immune system when exposed to the infectious environment may influence the likelihood of producing aCL in adult life.

Aim: To compare the cost-effectiveness of dental sedation techniques used in the treatment of children, focusing on hospital-based dental general anaesthetic (DGA) and advanced conscious sedation in a controlled primary care environment., Methods: Data on fees, costs and treatment pathways were obtained from a primary care clinic specialising in advanced sedation techniques. For the hospital-based DGA cohort, data were gathered from hospital trusts in the same area. Comparison was via an average cost per child treated and subsequent sensitivity analysis., Results: Analysing records spanning one year, the average cost per child treated via advanced conscious sedation was pound245.47. As some treatments fail (3.5% of cases attempted), and the technique is not deemed suitable for all patients (4-5%), DGA is still required and has been factored into this cost. DGA has an average cost per case treated of pound359.91, 46.6% more expensive than advanced conscious sedation. These cost savings were robust to plausible variation in all parameters., Conclusion: The costs of advanced conscious sedation techniques, applied in a controlled primary care environment, are substantially lower than the equivalent costs of hospital-based DGA, informing the debate about the optimum way of managing this patient group.

Background: Current American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) treatment guidelines recommend metformin (which does not promote weight gain) as the first-line antihyperglycaemic drug for patients with type 2 diabetes. However, when metformin fails, the recommended add-on treatment options (sulphonylureas, glitazones and basal insulin) can lead to significant weight gain. This article reviews the effect on body weight of current treatments for type 2 diabetes and discusses the potential impact of weight gain in this patient group., Scope: MEDLINE searches were performed to evaluate the prevalence and impact of changes in body weight in type 2 diabetes (articles published between January 1966 and August 2006) and the effects of sulphonylureas, glitazones, insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors and incretin analogs on body weight in these patients (search between January 2004 and September 2006)., Findings: Weight gain in general affects not only the physiological capability of patients with diabetes to achieve glycaemic control, but also their psychological well-being, quality of life and persistence with antihyperglycaemic treatment. Excess body weight and obesity in patients with diabetes are also associated with increased healthcare resource utilisation. Development of obesity is also associated with increased cardiovascular risk, although a link between drug-induced weight gain per se and increased cardiovascular risk has not been established. Initial clinical trial experience with the new oral DPP-4 inhibitors such as sitagliptin and vildagliptin suggests that these agents are weight-neutral, while providing improved glycaemic control when added to metformin., Conclusions: Because currently available add-on treatments can cause weight gain, physicians initiating add-on therapy in patients who can no longer achieve glycaemic control with metformin are faced with the problem of improving glycaemic control while causing weight gain. Initial clinical trial experience with oral DPP-4 inhibitors such as sitagliptin and vildagliptin suggest that these agents may represent an important oral treatment option for weight-neutral, glycaemic control when added to metformin. The new oral DPP-4 inhibitors, therefore, represent a potentially important addition to the oral treatment options currently available for the management of type 2 diabetes mellitus. Long-term clinical trials are now required to evaluate the relative risk/benefit profile of these drugs compared with the established antihyperglycaemic drug classes.

A novel, in vitro bioassay for detection of the botulinum type B neurotoxin in a range of media was developed. The assay is amplified by the enzymic activity of the neurotoxin's light chain and includes the following three stages: first, a small, monoclonal antibody-based immunoaffinity column captures the toxin; second, a peptide substrate is cleaved by using the endopeptidase activity of the type B neurotoxin; and finally, a modified enzyme-linked immunoassay system detects the peptide cleavage products. The assay is highly specific for type B neurotoxin and is capable of detecting type B toxin at a concentration of 5 pg ml(-1) (0.5 mouse 50% lethal dose ml(-1)) in approximately 5 h. The format of the test was found to be suitable for detecting botulinum type B toxin in a range of foodstuffs with a sensitivity that exceeds the sensitivity of the mouse assay. Using highly specific monoclonal antibodies as the capture phase, we found that the endopeptidase assay was capable of differentiating between the type B neurotoxins produced by proteolytic and nonproteolytic strains of Clostridium botulinum type B.

Currently the only accepted method for the detection of botulinum neurotoxin in contaminated samples is the mouse bioassay. Although highly sensitive this test has a number of drawbacks: it is expensive to perform, lacks specificity and involves the use of animals. With increasing resistance to such animal tests there is a need to replace the bioassay with a reliable in vitro test. Over the past six years it has been demonstrated that all the botulinum neurotoxins act intracellularly as highly specific zinc endoproteases, cleaving proteins involved in the control of secretion of neurotransmitters. In the work described, this enzymatic activity has been utilised in assay formats for the detection in foods of neurotoxin of the serotypes involved in food-borne outbreaks in man. These assays have been shown to have a greater sensitivity, speed and specificity than the mouse bioassay. It is envisaged that such assays will prove realistic alternatives to animal-based tests.

Currently the only accepted method for the detection of botulinum neurotoxin in contaminated samples is the mouse bio-assay. Although highly sensitive this test has a number of drawbacks: it is expensive to perform, lacks specificity and involves the use of animals. With increasing resistance to such animal tests there is a need to replace the bio-assay with a reliable in vitro test. Over the past six years it has been demonstrated that all the botulinum neurotoxins act intracellularly as highly specific zinc endoproteases, cleaving proteins involved in the control of secretion of neurotransmitters. In the work described, this enzymatic activity has been utilised in assay formats for the detection in foods of neurotoxin from the serotypes involved in food-borne outbreaks in man. These assays have been shown to have a greater sensitivity, speed and specificity than the mouse bio-assay. It is envisaged that such assays will prove realistic alternatives to animal based tests.