Surveillance for work-related hearing loss in the UK: OSSA and OPRA 1997-2000

Surveillance data on occupational audiological disorders have been collected by the Occupational Surveillance Scheme for Audiological Physicians (OSSA) since October 1997 and by the Occupational Physicians Reporting Activity (OPRA) from January 1996. During the 3 years ending in September 2000, a total of 1620 new cases were received from consultant audiological physicians; 988 new cases were estimated from reports by occupational physicians in the period from October 1997 to September 2000. The annual incidence of occupational noise-induced hearing loss (NIHL) was 1.94 and 1.23 per 100 000 workers for the OSSA and OPRA schemes, respectively. The median age at diagnosis with NIHL was 59 years in OSSA reports and 50 years in OPRA; nearly all cases were seen in men (95.6 and 92.5% male cases for OSSA and OPRA, respectively). High incidence rates based on OSSA reports were seen in foundry labourers (64.0 per 100 000 employed), coal gas and coke oven furnace workers (54.6), workers in transport and communication (43.1), metal workers (31.3), and members of the armed forces (28.3). Data from occupational physicians point to high rates in sawyers and woodworking machinists, metal furnace workers, coach and carriage builders, maintenance fitters, and engineering labourers. Among workers aged < or =45 years, those in manufacturing and the armed forces were prominent. The long latency of occupational hearing loss makes surveillance difficult, but consistent patterns in occupational risk suggest targets for preventive efforts.     

Risks to the public from historical releases of radionuclides and chemicals at the Rocky Flats Environmental Technology Site

This paper summarizes the methods and results of estimating risks of cancer incidence resulting from plutonium, carbon tetrachloride, and beryllium releases from operations at the Rocky Flats Environmental Technology Site, near Denver, Colorado, from 1953 through 1989. The key findings show that people who lived near the facility were exposed to plutonium mainly through inhalation during routine operations, from a major fire in 1957, and from plutonium resuspended from contaminated soil from an outdoor drum storage area, called the 903 Area. Results were presented for five exposure scenarios that were location-independent. Individuals described by the laborer scenario received the highest risk of all scenarios considered. Upper bound (95th percentile) incremental lifetime cancer incidence risks for the laborer scenario were in about the 10(-4) range (1 chance in 10,000) for developing cancer from Rocky Flats plutonium releases during a lifetime. At the 5th percentile level, the maximum cancer risk was about 10(-7) (1 chance in 10 million) for developing cancer during a lifetime. Estimated cancer risks at the 95th percentile level are within the range of for acceptable risks established by the US Environmental Protection Agency of 10(-6) to 10(-4). Carbon tetrachloride was found to be the chemical that presented the highest risk to the public. The 5th and 95th percentile risk values for exposure to carbon tetrachloride were 9.2x10(-7) and 2.5x10(-5), respectively.     

Bioterrorism-related anthrax surveillance,Connecticut, September-December, 2001

On November 19, 2001, a case of inhalational anthrax was identified in a 94-year-old Connecticut woman, who later died. We conducted intensive surveillance for additional anthrax cases, which included collecting data from hospitals, emergency departments, private practitioners, death certificates, postal facilities, veterinarians, and the state medical examiner. No additional cases of anthrax were identified. The absence of additional anthrax cases argued against an intentional environmental release of Bacillus anthracis in Connecticut and suggested that, if the source of anthrax had been cross-contaminated mail, the risk for anthrax in this setting was very low. This surveillance system provides a model that can be adapted for use in similar emergency settings.     

Transient relaxation of rat mesenteric microvessels by ceramides

We have investigated the vasodilating effects of D-erythro-C2-ceramide (C2-ceramide) in methoxamine-contracted rat mesenteric microvessels. C2-ceramide (10 - 100 microM) caused a concentration-dependent, slowly developing relaxation which reached maximum values after approximately 10 min and partially abated thereafter. Endothelium removal or inhibitors of guanylyl cyclase (3 microM ODQ), protein kinase A (10 microM H7, 1 microM H89) and various types of K(+) channels (10 microM BaCl(2), 3 mM tetraethylammonium, 30 nM charybdotoxin, 30 nM iberiotoxin, 300 nM apamine, 10 microM glibenclamide) had only small if any inhibitory effects against C2-ceramide-induced vasodilation, but some of them attenuated vasodilation by sodium nitroprusside or isoprenaline. A combination of ODQ and charybdotoxin almost completely abolished C2-ceramide-induced vasodilation. A second administration of C2-ceramide caused a detectable but weaker relaxation. L-threo-C2-ceramide (100 microM), which should not be a substrate to ceramide metabolism, had no biphasic time course. The ceramidase inhibitor (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol (100 microM) alone caused some vasodilation, indicating vasodilation by endogenous ceramides, and also hastened relaxation by exogenous C2-ceramide. The late-developing reversal of C2-ceramide-induced vasodilation was absent when alpha-adrenergic tone was removed by addition of 10 microM phentolamine. We conclude that C2-ceramide relaxes rat resistance vessels in an endothelium-independent manner which is prevented only by combined inhibition of guanylyl cyclase and charybdotoxin-sensitive K(+) channels. The vasodilation abates with time partly due to desensitization of the ceramide response and partly due to metabolism of C2-ceramide to an inactive metabolite.     

Conformationally constrained nicotines: polycyclic,bridged, and spiro-annulated analogues as novel ligands for the nicotinic acetylcholine receptor

A set of novel nicotine-related, conformationally constrained compounds, including tetracyclic, bridged (4), and tricyclic, spiro-annulated (5) structures, were synthesized in a straightforward manner and optically resolved in a convenient fashion with (+)- and (-)-O,O'-di-p-toluoyltartaric acids. Absolute configurations were determined by X-ray crystallography. These compounds were evaluated for their ability to displace [(3)H]cytisine in a rat forebrain preparation and compared to (-)-nicotine. Three substances emerged with high affinity in the low nanomolar range. Moreover, one of these compounds ((+)-5b) showed not only high binding affinity (K(i) = 4.79 nM) but also significant enantioselectivity over its antipode (K(i) = 148 nM), supporting the hypothesis that conformational restraint can lead to high-affinity ligands, which are stereochemically discriminated by the nicotinic acetylcholine receptor and may feature optimum locations of the active sites of the pharmacophore.     

Cytochrome P450 CYP1A1 accumulates in the cytosol of kidney and brain and is activated by heme

Cytochrome P450 CYP1A1 is expressed in most tissues. In brain and kidney, its function remains unclear because its enzymatic activity is barely measurable. Here, we report on the localization of CYP1A1 in the cytosol of kidney and brain, as revealed by immunoblotting with anti-CYP1A1 antibodies and by 7-ethoxyresorufin deethylation (EROD). Hematin (8 microM) added in vitro to cytosol increased the EROD-activity 10-fold in brain olfactory bulb and 7-fold in kidney, presumably by reconstitution of apocytochrome. Succinylacetone, an inhibitor of heme biosynthesis, increased the ratio of cytosolic to microsomal EROD activity of transiently expressed CYP1A1 in COS-1 cells from 1:1 to nearly 6:1. This indicates a strong decrease of microsomal activity with increasing succinylacetone concentration. CYP1A1 activities correlated with CYP1A1 protein assessed by immunoblotting. We conclude that the availability of heme is a limiting factor of P450 function in extrahepatic tissue. Our data further suggest that reduced availability of heme limits the incorporation of P450s into brain endoplasmic reticulum. These observations are important when assessing the function of P450s in extrahepatic tissue.     

Scale-up of polymerization processes

Scale-up and/or scale-down procedures are crucial during the development of chemical processes. These procedures should be integrated to form a multidisciplinary approach encompassing several branches of science and engineering. The challenge is to find a balance between chemistry, design, environment, hygiene and safety (EHS) compliance and economic factors. The iterative process of scale-up procedures also requires concept discrimination at early stages of process development. Scale-up studies should predict the reactor behavior and the quality and properties of a product from laboratory and pilot plant to full scale; however, not every pilot scale presents a valid industrial scaled-down size. A rational mathematical model describing the process reasonably well for large scale is important for designing industrial processing units, but this is only feasible if a phenomenological understanding is achieved, and if the necessary constants and parameters are estimated accurately. An accomplished process development procedure must lead to products presenting the same properties at both small and large scale.     

Globulixanthones A and B,two new cytotoxic xanthones with isoprenoid groups from the root bark of Symphonia globulifera

Bioassay-guided fractionation of a root bark extract of Symphonia globulifera has yielded, in addition to stigmasterol, two new xanthones with isoprenoid units, named globulixanthones A (1) and B (2). The structures of these compounds have been elucidated by spectroscopic means. They possess significant cytotoxicity in vitro against the KB cell line.     

Myocardial angiogenesis resulting in functional communications with the left cavity induced by intramyocardial high-frequency ablation: histomorphology of immediate and long-term effects in pigs

A previous study in rabbit hearts demonstrated the feasibility of creating transmyocardial channels by application of temperature-regulated high-frequency (HF) energy. Feasibility of creating non-transmural channels using a transvascular approach was tested in 14 pigs which were followed for 1 h, and 3 and 9 weeks (group A, B and C). Myocardial channels were found to be highly reproducible and patent in more than two thirds in group A. Channels were replaced by connective tissue during follow-up which contained newly formed small vessels. A functional communication between the left ventricular cavum and newly formed vessels of the channel remnants could be demonstrated in one heart of group C. Thus, intramyocardial HF ablation can be performed with high reproducibility to induce local angiogenesis.