Autonomous detection of aerosolized biological agents by multiplexed immunoassay with polymerase chain reaction confirmation.

The autonomous pathogen detection system (APDS) is an automated, podium-sized instrument that continuously monitors the air for biological threat agents (bacteria, viruses, and toxins). The system has been developed to warn of a biological attack in critical or high-traffic facilities and at special events. The APDS performs continuous aerosol collection, sample preparation, and detection using multiplexed immunoassay followed by confirmatory PCR using real-time TaqMan assays. We have integrated completely reusable flow-through devices that perform DNA extraction and PCR amplification. The fully integrated system was challenged with aerosolized Bacillus anthracis, Yersinia pestis, Bacillus globigii, and botulinum toxoid. By coupling highly selective antibody- and DNA-based assays, the probability of an APDS reporting a false positive is extremely low.

A genetic polymorphism of the alpha2-adrenergic receptor increases autonomic responses to stress.

We hypothesized that individual differences in autonomic responses to psychological, physiological, or environmental stresses are inherited, and exaggerated autonomic responsiveness may represent an intermediate phenotype that can contribute to the development of essential hypertension in humans over time. alpha(2)-Adrenergic receptors (alpha(2)-ARs), encoded by a gene on chromosome 10, are found in the central nervous system and also mediate release of norepinephrine from the presynaptic nerve terminals of the peripheral sympathetic nervous system and the exocytosis of epinephrine from the adrenal medulla. We postulated that, because this receptor mediates central and peripheral autonomic responsiveness to stress, genetic mutations in the gene encoding this receptor may explain contrasting activity of the autonomic nervous system among individuals. The restriction enzyme Dra I identifies a polymorphic site in the 3'-transcribed, but not translated, portion of the gene encoding the chromosome 10 alpha(2)-AR. Southern blotting of genomic DNA with a cDNA probe after restriction enzyme digestion results in fragments that are either 6.7 kb or 6.3 kb in size. Transfection studies of these two genotypes resulted in contrasting expression of a reporter gene, and it is suggested from these findings that this is a functional polymorphism. In a study of 194 healthy subjects, we measured autonomic responses to provocative motion, a fall in blood pressure induced by decreasing venous return and cardiac output, or exercise. Specifically, we measured reactions to 1) Coriolis stress, a strong stimulus that induces motion sickness in man; 2) heart rate responses to the fall in blood pressure induced by the application of graded lower body negative pressure; and 3) exercise-induced sweat secretion. In all of these paradigms of stress, subjective and objective evidence of increased autonomic responsiveness was found in those individuals harboring the 6.3-kb allele. Specifically, volunteers with the 6.3-kb allele had greater signs and symptoms of motion sickness mediated by the autonomic nervous system after off-axis rotation at increasing velocity (number of head movements a subject could complete during rotation before emesis +/- SE: 295 +/- 18 vs. 365 +/- 11; P = 0.001). They also had greater increases in heart rate in responses to the lower body negative pressure-induced fall in blood pressure (increase in heart rate +/- SE: 3.0 +/- 0.4 vs. 1.8 +/- 0.3; P = 0.012), and the 6.3-kb group had higher sweat sodium concentrations during exercise (mean sweat sodium concentration in meq/l over 30 min of exercise +/- SE: 43.2 +/- 7.1 vs. 27.6 +/- 3.4; P < 0.05). This single-nucleotide polymorphism may contribute to contrasting individual differences in autonomic responsiveness among healthy individuals.

GPs' compliance with health and safety legislation and their occupational health needs in one London health authority.

This survey assessed general practitioners' (GPs') knowledge of and compliance with, health and safety legislation and occupational health guidance in one London health authority. The response rate was 85%. Although the majority of practices were aware of the most important piece of legislation--The Management of Health and Safety at Work Regulations, 1992--less than one in ten practices had carried out the required systematic risk assessments. Compliance with other health and safety legislation and related employment issues was also poor. The health of GPs and their staff may be at risk and these general practices may be vulnerable to prosecution by the Health and Safety Executive.

Ethnic differences in titratable acid excretion and bone mineralization.

PURPOSE: To test our hypothesis that differences in urinary calcium excretion among blacks and whites may be secondary to ethnic variations in acid (H(+)) metabolism and to prove that increases in titratable acid excretion would be found among individuals predisposed to the development of stress fractures. METHODS: We administered 8 g NH(4)Cl acutely to 11 black and 18 white healthy volunteers and measured urinary sodium, calcium, and acid excretions. We measured the Na(+)/H(+) antiporter activity using acid-loaded platelets as surrogate markers for this exchanger expressed in renal epithelial cells. We also compared differences in titratable acid excretion among a cohort of subjects with, and without, a history of stress fracture. RESULTS: NH(4)Cl-induced increases in titratable urinary acid correlated with changes in the renal excretion of calcium and sodium, and stimulated acid excretion correlated with basal acid loss. Despite comparable changes in plasma pH, whites, when compared to blacks, had much greater basal acid excretion and NH(4)Cl-induced acid excretion. Whites also had much greater baseline calcium excretion rates when compared to blacks. Following acid loading, whites continued to exhibit greater calcium excretion rates than blacks. Acid loading significantly decreased sodium excretion in whites but not in blacks. Blacks also had significantly attenuated Na(+)/H(+) exchange activity. In a cohort of resting, athletic students, we found enhanced basal H(+) and phosphate excretion among subjects who experienced stress fractures during their rigorous physical training when compared to those individuals who did not. CONCLUSION: Blacks may have a greater endogenous buffering capacity than whites, or the reported ethnic differences in sodium and calcium excretion rates between blacks and whites may be secondary to racial variations in renal H(+) excretion. We conclude that both ethnic differences in bone mineralization and bone integrity in athletes are mediated by heritable differences in titratable acid excretion.

Treatment of Elderly Hypertensive Patients With Diabetes, Renal Disease, and Coronary Heart Disease.

Aging in Westernized industrialized societies is associated with an increasing prevalence of hypertension, type II diabetes mellitus, renal disease, and atherosclerotic vascular disease. This increase in the chronic disease processes in industrialized societies is related, in part, to increasing obesity, reduced physical activity, medications such as nonsteroidal anti-inflammatory agents, and other environmental influences. Hypertension in the elderly is characterized by high peripheral vascular resistance, reduced baroreflex sensitivity, a low renin state with reduced cardiac output/increased hypertrophy, reduced intravascular volume, and an increased propensity to salt-sensitivity. Initial antihypertensive therapy in the elderly patient should be based on attempts to affect hygienic measures such as weight reduction, decreased salt and fat intake, and a careful aerobic exercise program. The initial antihypertensive drugs of choice are low doses of diuretics, which have been shown to reduce cardiovascular mortality in the elderly. Low doses of diuretics do not substantively affect carbohydrate and lipid metabolism. Lipid abnormalities in the elderly should generally be treated in a similar fashion to those in the middle-aged individual. Compliance with medical therapy in the elderly patient has been demonstrated to be relatively good.