Biomedical subjects

David Hands

Publications and source records attributed to David Hands.

4 recordsLinked to original sources

PubMed2006

Practical asymmetric synthesis of a gamma-secretase inhibitor exploiting substrate-controlled intramolecular nitrile oxide-olefin cycloaddition.

A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is described. As the key transformation, a highly diastereoselective intramolecular nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four operations. Other aspects of the route include a highly stereoselective reduction of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical resolution, a dianion cyclization to construct a sultam ring, and the alpha-alkylation of a sultam with excellent diastereoselectivity. In each instance, the relative stereochemistry was evolved by way of substrate-based induction with > or = 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were obtained, without recourse to chromatography, by way of 10 isolated intermediates and in 13% overall yield.

Alkenes↗

PubMed2003

Control methods for mineral oil mists.

Effective mist collection is important, but it is not the only determinant of mist concentration in plant air. Oil-based metalworking fluids such as straight and soluble oils contain semivolatile hydrocarbons. When these fluids form a mist, their semivolatile components partition between the vapor and mist phases depending on the makeup of the mist and on local conditions. This article addresses the relationship between the concentrations of semivolatile hydrocarbons in the vapor and mist phases using theory for partitioning developed in the field of atmospheric chemistry. Mist can be removed effectively in a collector that uses a HEPA filter as its final collection stage. Acceptable HEPA lifetime requires effective upstream stages that reduce mist loading to the HEPA; furthermore, acceptable HEPA performance requires that it be installed and maintained properly. Collectors designed to remove mist do not remove vapor, and as collector exhaust mixes into cooler plant air that already contains some mist, vapor from the collector can repartition to increase the mist concentration in the plant. Assessing the effect of vapor-to-mist repartitioning is complicated; however, repartitioning may be important for many of the compounds contained in oil-based metalworking fluids. Conditions that minimize vapor-to-mist repartitioning, such as ventilating the plant with clean outdoor air, increasing plant temperature, or controlling the release of vapor, may also be expensive, uncomfortable to plant occupants, or impractical from an engineering standpoint. As a result, very low mist concentrations in plant air may be difficult to attain.

Air Pollutants, Occupational↗

PubMed2003

Inpatient hospital admission rates for nonmalignant respiratory disease among workers exposed to metal removal fluids at a U.S. automobile manufacturer.

This study was undertaken to determine the impact of exposure to metal removal fluids (MRFs) on the respiratory health of exposed workers. The outcome measure selected was the rate of hospital admissions for nonmalignant respiratory disease episodes as determined from healthcare insurance claims data. A cohort of MRF-exposed employees was assembled from 11 manufacturing facilities where MRFs were extensively used in the manufacture of automotive engines, transmissions, and other machined parts. The MRF-exposed cohort included 20,434 employees of such facilities who worked at any time from 1993 through 1997. A non-MRF-exposed cohort was assembled from other employees of the same company during the same time period, but working in warehouse operations and other manufacturing facilities that did not use MRFs or any known respiratory sensitizing agents. The non-exposed cohort included 8681 employees. The crude hospital admission rate for the MRF-exposed cohort was 44 percent higher than that of the non-exposed cohort over the 5-year study period (6.67 vs. 4.62 per 1000 person years at risk, p < 0.05). With age adjustment, the MRF population's rate was still 35 percent higher, and still statistically significant. A nested case-control study was also conducted to determine whether the risk of hospital admission increased with the level of MRF exposure in the population working in MRF plants. The industrial hygiene reconstruction found the levels of exposures of both cases and controls to be very low, with the vast majority of study subjects (more than 90%) having exposures of less than 0.5 mg/m(3). The case-control study did not find any association between increased levels of MRF exposure and risk of hospitalization. The study did document an elevated risk of hospitalization among a sizable population employed in manufacturing operations where MRFs are used.

Automobiles↗

PubMed2002

A systematic review of the clinical and economic impact of drug information services on patient outcome.

AIM: To establish what is known about the clinical and economic impact of drug information (DI) services on patient outcome. METHOD: A systematic review and critical appraisal of world literature on work conducted by Drug Information Centres and UK Schools of Pharmacy. RESULTS: Six relevant published articles were recovered--three from the UK; two from the US and one from Canada; just one was prospective in design. Four were single-centre and two were multi-centre studies. Four studies relied heavily on questionnaire surveys of the enquirer to establish an effect; only one monitored patient outcome independently and used peer review to assess impact. CONCLUSION: The clinical and economic impact of drug information consultation and provision on patient care has not been investigated rigorously. A research methodology for such an investigation is suggested.

Algorithms↗