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D Whitfield

Publications and source records attributed to D Whitfield.

10 recordsLinked to original sources
PubMed2002

Activated protein C resistance in the absence of factor V Leiden mutation is a common finding in multiple myeloma and is associated with an increased risk of thrombotic complications.

Thromboembolism is not uncommon in multiple myeloma (MM) patients on treatment, but its pathogenesis remains poorly understood. We report the results of a prospective randomized trial of 62 newly diagnosed MM patients tested at baseline for hypercoagulability and treated with intensive chemotherapy with or without thalidomide in a randomized fashion. During the induction phase, 12 patients (19%) developed evidence of deep venous thrombosis (DVT), which was significantly more common in the thalidomide arm (36%) than in the control group (3%) (P = 0.001). Fourteen patients (23%) were found to have a baseline-reduced response to activated protein C (APC) in the absence of factor V Leiden mutation. Using a Kaplan-Meier analysis, a significantly higher proportion of patients with APC resistance developed DVT (5/14 versus 7/38; P = 0.04) irrespective of thalidomide administration. The risk of DVT was highest (50%) in patients with APC resistance on thalidomide. None of the patients with normal APC response and not receiving thalidomide developed DVT. In conclusion, in this series, acquired APC resistance was present in almost one-quarter of newly diagnosed myeloma patients and significantly increased the risk of DVT.

Activated Protein C Resistance↗
PubMed1994

Metabolism of vesnarinone by activated neutrophils: implications for vesnarinone-induced agranulocytosis.

Vesnarinone is an important new drug that significantly decreases mortality rates in severe congestive heart failure; however, its use is associated with a relatively high incidence (approximately 1%) of agranulocytosis. The authors studied its metabolism by activated neutrophils, the target for this toxicity, and evidence pointed to a pathway that involved a reactive iminium ion. Hydrolysis of the iminium ion led to a reactive quinone imine. The same pathway was observed with a combination of myeloperoxidase/hydrogen peroxide/chloride, the major oxidizing system of neutrophils, or hypochlorous acid, which is generated by this system. Activation of the neutrophils could be achieved by phorbol ester or by influenza vaccine and there is evidence to suggest that the administration of influenza vaccine during vesnarinone therapy may increase the risk of agranulocytosis. Incubation of radiolabeled vesnarinone with activated neutrophils led to covalent binding of almost 5% of the drug to the cells. Both the iminium ion and quinone imine generated by hypochlorous acid could be trapped with glutathione. It was proposed that these reactive metabolites, generated by neutrophils or neutrophil precursors in the bone marrow, may be responsible for the vesnarinone-induced agranulocytosis. Factors such as infection or vaccination that activate neutrophils may increase the risk of agranulocytosis.

Agranulocytosis↗
PubMed1991

A simple device for the objective measurement of activity.

The activity of small experimental animals is difficult to quantify without prolonged observation and note-taking. We describe a relatively cheap and easily constructed device for monitoring and recording activity. Appropriate modifications make the basic device suitable for limited field applications.

Animals↗
PubMed1984

Two cases of falciparum malaria acquired in Britain.

Two cases of severe falciparum malaria contracted in the United Kingdom occurred in residents of Sussex, living 10 and 15 km from Gatwick airport. One patient was the landlord of a public house much frequented by aircrew, and the other was the wife of a worker at the airport, who travelled close to the public house on the probable date she contracted her infection. Transmission was most probably due to the bite of an infected imported tropical anopheline mosquito transported in a vehicle from the aircraft to the site of transmission during the very hot and humid weather of July 1983. Prevention of further cases depends on increased diligence in "blocks-away" destruction of insects in aircraft flying from endemic areas, but there is a need for more study of acceptable alternative ways of delivering the insecticide. This "airport malaria" is well recognised on the continent, and physicians should be aware of its existence in those who have not travelled abroad but live or work near international airports.

Aircraft↗
PubMed1971

British standards and ergonomics.

A review is presented of British Standards having some relevance to ergonomics, and the Standards selected are classified into the various areas of ergonomics. Certain areas are discussed in some detail, in order to point out cases where practical problems, current standardisation and ergonomics knowledge are not wholly compatible. There is a brief discussion of the aims and methods of the British Standards Institution.

Journal Article↗