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Biomedical subjects

Matthew Price

Publications and source records attributed to Matthew Price.

5 recordsLinked to original sources

Rapid, real-time detection of acute HIV infection in patients in Africa.

BACKGROUND: We conducted a prospective study to evaluate methods of detecting clients with sexually transmitted diseases (STDs) who were acutely coinfected with human immunodeficiency virus (HIV) in Lilongwe, Malawi. METHODS: After informed consent was obtained, all clients with acute STDs were offered voluntary HIV counseling and testing by 2 rapid antibody tests. Samples from rapid test-negative or -discordant subjects were pooled (50 : 5 : 1) and tested for HIV RNA. Western blots were performed on all rapid test-discordant specimens with detectable HIV RNA. A subset of specimens received p24 antigen testing with standard and/or ultrasensitive methods. Patients with possible acute HIV infection were followed to confirm seroconversion. RESULTS: A total of 1450 clients (34% female and 66% male) agreed to testing, of whom 588 (40.55%) had established HIV infection and 21 (1.45%) had acute infection. Discordant rapid antibody tests identified 7 of 21 (33.3% sensitivity), standard p24 antigen identified 12 of 16 (75% sensitivity), and ultrasensitive p24 antigen identified 15 of 17 (88% sensitivity) acute cases. By definition, the sensitivity of the RNA assay was 100%. CONCLUSIONS: Real-time pooled RNA testing for the detection of acute HIV infection is feasible in resource-limited settings. However, parallel rapid testing and p24 antigen testing are technologically simpler and together may detect approximately 90% of acute cases.

Acute Disease↗

The role of presence in virtual reality exposure therapy.

A growing body of literature suggests that virtual reality is a successful tool for exposure therapy in the treatment of anxiety disorders. Virtual reality (VR) researchers posit the construct of presence, defined as the interpretation of an artificial stimulus as if it were real, to be a presumed factor that enables anxiety to be felt during virtual reality exposure therapy (VRE). However, a handful of empirical studies on the relation between presence and anxiety in VRE have yielded mixed findings. The current study tested the following hypotheses about the relation between presence and anxiety in VRE with a clinical sample of fearful flyers: (1) presence is related to in-session anxiety; (2) presence mediates the extent that pre-existing (pre-treatment) anxiety is experienced during exposure with VR; (3) presence is positively related to the amount of phobic elements included within the virtual environment; (4) presence is related to treatment outcome. Results supported presence as a factor that contributes to the experience of anxiety in the virtual environment as well as a relation between presence and the phobic elements, but did not support a relation between presence and treatment outcome. The study suggests that presence may be a necessary but insufficient requirement for successful VRE.

Adaptation, Psychological↗

Development of next generation medical countermeasures to nerve agent poisoning.

Medical countermeasures provide a key role in the UK integrated approach to chemical defence and are aimed at preventing or mitigating the effects of exposure to nerve agents. It is UK policy that medical countermeasures will be licensed products. Demonstration of efficacy relies on extrapolation of animal-derived data to man which means that species selection is extremely important. For the foreseeable future it is likely that a combination of pretreatment and therapy will be required to provide protection against nerve agent poisoning. There is a longer-term aspiration to develop a post poisoning-therapy which would reduce the reliance on pretreatment, prevent or mitigate the effects of exposure to all nerve agents and decrease the requirement for three autoinjectors. Immediate therapy comprising physostigmine (0.2mg/kg), hyoscine hydrobromide (4mg/kg) and HI-6 (93.6mg/kg) protected all animals against the lethal effects of a supralethal dose of GD, when given 1min after nerve agent poisoning in the absence of any pretreatment. In contrast when hyoscine hydrobromide was replaced with hyoscine methyl nitrate most of the animals died within 24h, whereas when an equal mixture of hyoscine hydrobromide and hyoscine methyl nitrate was used all the animals survived. None of these animals had an intussusception. It would not be possible to deliver these doses of HI-6 to a human from a single autoinjector device. Recent studies have shown that a lower dose of HI-6 (7mg/kg) which can be delivered via an autoinjector, in combination with physostigmine and hyoscine hydrobromide provides good protection against the lethal effects of a supralethal dose of GD. A number of animals died between 6 and 24h and had an intussusception. The surviving animals did not begin to regain weight until 48h after poisoning. In contrast when a mixture of hyoscine hydrobromide and hyoscine methyl nitrate was used, one animal died within 15min, the other animals all survived, regained weight from 24h and did not have an intussusception. These studies will now be extended to include other agents and will be taken forward to studies in non-human primates where the incidence of intussusception will be closely monitored.

Animals↗

A novel approach for medical countermeasures to nerve agent poisoning in the guinea-pig.

This study forms part of a larger programme of work aimed at developing improved medical countermeasures for nerve agent poisoning with less reliance on pretreatment. Therapy with N(6)-cyclopentyladenosine (CPA), physostigmine, hyoscine and HI-6 protected guinea-pigs against the incapacitating and lethal effects of a supralethal challenge of soman (135 microg/kg) when given 1 min after poisoning. CPA, however has well-recognised side effects that are likely to preclude it being licensed for use in humans so further refinements were made to the doses of the other therapy components to improve efficacy in the absence of CPA. An immediate therapy comprising physostigmine (0.2 mg/kg), hyoscine (4 mg/kg) and HI-6 (93.6 mg/kg), when given 1 min after nerve agent, provided good protection against the lethal effects of GA, GB, GD, GF and VX poisoning and reduced the duration of the signs of incapacitation and hypothermia. In the case of GA and GB poisoning some animals exhibited a short period of substantial incapacitation. Most animals continued to gain weight over the following 6 days without the need for further medical intervention. In the case of GA poisoning further medical intervention would be needed to ensure the longer term survival of all animals and it is likely that in the battlefield situation further medical treatment would be available within 2-4 h. The drug combination described in this paper protects against supralethal doses of a range of nerve agents, with minimal incapacitation in the absence of any pretreatment. Further modification and refinement of this therapy is required for human use and it may provide a way forward for development of medical countermeasures for the treatment of organophosphate poisoning in the wider community should there be a need.

Animals↗