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Biomedical subjects

A W Wilson

Publications and source records attributed to A W Wilson.

At least 19 recordsLinked to original sources

Attenuation of experimental arthritis in TRPV1R knockout mice.

The Transient Receptor Potential Vanilloid 1 (TRPV1R) is a ligand-gated, non-selective cation channel expressed predominantly by sensory neurons. TRPV1Rs respond to a variety of noxious stimuli including capsaicin, intense heat and acid. These factors, combined with behavioral studies, show that TRPV1Rs are involved in nociception. The aim of our study was to determine whether TRPV1Rs play a role in the development and maintenance of inflammation and mechanical hyperalgesia by studying the development of unilateral joint inflammation in TRPV1R-/- mice. Knee joints of TRPV1R-/- or wild-type (WT) mice were injected with FCA (200 microg) under temporary anesthesia, and the resulting inflammation and hyperalgesia measured for 35 days. Histological analysis was performed on joints at the end of the study. TRPV1R-/- mice developed mild joint swelling which was significantly less than that obtained in WT mice (P < 0.05, Mann-Whitney). The ratio of the weight distribution between the hind limbs in TRPV1R-/- mice was also significantly less than in WT mice (P < 0.05, Mann-Whitney). Neither swelling nor hypersensitivity was completely absent in the knockout mice, indicating either that other mechanisms are involved or that a compensatory mechanism operates in TRPV1R-/- mice. These results suggest that TRPV1 receptors are important for the development of joint inflammation and the associated mechanical hypersensitivity observed in this model.

Animals↗

A predictive tool for the self-management of diabetes (Librae): evaluation using a continuous glucose monitoring system.

AIMS: Diabetes self-management involves a difficult balancing act between insulin, food and exercise. The challenge is to develop innovative, validated algorithms to aid patient decision-making and optimize glycaemic control. 'Librae' is a computerized diabetes simulator in diary format, developed as an educational predictive tool for patients, reducing 'trial and error' by allowing patients to simulate and experiment with dietary or insulin adjustments on a 'body double'. We have evaluated the predictive ability of Librae using continuous blood glucose monitoring (CGMS). METHODS: Patients with Type 1 Diabetes attending the Paediatric Clinic were invited to use 'Librae' for 1 week and were then fitted with a CGMS for 72 h. The predictive ability of 'Librae' was compared with concurrent data obtained from the CGMS. RESULTS: Seven thousand nine hundred and sixty paired blood glucose values were obtained from the 11 patients who completed the study. 'Librae' underestimated the measured CGMS values, the error having a positive mean of 0.35 mmol/l (95% confidence interval 0.22-0.48 mmol/l). However, Librae tended to overestimate at low levels of blood glucose readings, and underestimate at high levels of blood glucose readings. CONCLUSION: The modelled values of 'Librae' correlated well with the CGMS data, but clinically unacceptable errors occurred at extremes of blood glucose levels. Concurrent CGMS recordings have provided a large data set to modify and improve the existing Librae model and patient feedback has led to improvements in its usability. Librae may provide a useful tool to improve diabetes self-management education and optimize glycaemic control.

Adolescent↗

Multiple synchronous and metachronous neoplasms of the parotid gland: the Chichester experience.

Parotid neoplasms are usually solitary and multiple tumours occurring in an individual are uncommon. The incidence and implications of multiple synchronous and metachronous tumours remains relatively unknown. We reviewed the case notes of 606 patients who had parotidectomies for neoplastic lesions over a 30 year period and identified 30 patients (5%) with multiple primary tumours. There were 24 patients with synchronous tumours and 6 with metachronous tumours. Sixteen of the synchronous tumours (67%) were ipsilateral, whereas all six metachronous tumours were contralateral. Preoperative examination was effective at detecting bilateral tumours but poor at detecting multiple ipsilateral tumours. Multiple tumours were likely to be of the same histology (n=24, 80%) and Warthin's was by far the most common multiple tumour. Ipsilateral tumours of differing histological types and identical tumours other than Wartin's were uncommon. All but one patient had superficial parotidectomies and there were no recurrences.

Adenocarcinoma↗

Another use of the Foley catheter: retraction for operations on the floor of mouth and ventral aspect of the tongue.

A Foley catheter that is passed through the nose and sutured to the tip of the tongue can be used to facilitate retraction for operations on lesions on the ventral aspect of the tongue and the floor of the mouth. It provides excellent access and is simple, inexpensive, atraumatic, minimises frustration, reduces the operating time, and eliminates some of the difficulties associated with the use of metal retractors.

Catheterization↗

Transmasseteric antero-parotid approach for open reduction and internal fixation of condylar fractures.

The morbidity that results from surgical approaches to the condylar neck, and the time-consuming nature of the operation inhibits many surgeons from using open reduction and internal fixation for the treatment of condylar fractures. The many approaches that have been described stand testimony to the disadvantages of the individual techniques. The most common problems are limited access and injury to the facial nerve. We describe the transmasseteric antero-parotid (TMAP) technique, which offers swift access to the condylar neck while substantially reducing the risk to the facial nerve and eliminating the complications associated with transparotid approaches.

Bone Plates↗

Surgical management of incompletely excised basal cell carcinomas of the head and neck.

We made a retrospective audit of all basal cell carcinomas excised in the Maxillofacial Units at St. Richard's Hospital, Chichester and the Worthing and Southlands NHS Trust between 1990 and 1999. A total of 3795 BCCs were excised. Of these, 3560 were completely excised (93.8%) and 235 were incompletely excised (6.2%), which compares favourably with other series. Of these, 84 patients had further excision, 11 had radiotherapy, and 140 were kept under review. Residual tumour was present in 45% of the re-excised specimens. Of the 140 cases managed by observation, 21% recurred. Notably, 31% of patients in the observation cohort died of other causes without recurrence. Incomplete excision was significantly more likely (P < 0.001) if multiple lesions were excised at the time of operation. Involvement of multiple margins was not a significant risk factor for recurrence in the 'observed' cohort. This study shows that a flexible strategy, which balances observation, further excision and radiotherapy, is superior to any single approach.

Basal Cell Carcinoma↗

[Resuscitative transverse thoracotomy].

The technique of resuscitative transverse thoracotomy is for use in case of circulatory arrest in the trauma patient. This technique, performed after orotracheal intubation, is initiated by a 5th intercostal space thoracostomy in each mid-axillary line. If the circulatory arrest is not caused by a tension pneumothorax, bilateral thoracotomies in the 5th intercostal spaces with transverse transsection of the sternum is performed. Middle vertical incision of the pericardium allows the evacuation of a cardiac tamponade. This wide surgical access has proved simple to perform, even by non experienced operators. It allows digital control of a heart wound, cross-clamping of the thoracic descending aorta or of pulmonary hilum, rapid perfusion of warm fluids through the right auricle and the performance of bimanual internal cardiac massage.

Heart Arrest↗

Azoles for allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic Broncho-pulmonary Aspergillosis (ABPA) is hypersensitivity to the fungus Aspergillus Fumigatus that complicates patients with asthma and cystic fibrosis. The condition usually results in an increase in symptoms, a greater reliance on corticosteroids to control the disease process and may lead to a progressive decline in lung function. The mainstay of treatment for ABPA remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review is to determine the efficacy of azoles in the treatment of ABPA SEARCH STRATEGY: An initial search was carried out using the Cochrane Airways Group Asthma RCT register. The register was searched using the following terms: (asthma or wheeze) and (allergic bronchopulmonary aspergillosis or aspergillosis or allergic pulmonary aspergillosis or allergic fungal and disease or allergic mycotic and disease) and (azole or triazole or itraconazole or ketoconazole). SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard, for any duration or dose regimen in subjects with ABPA of any age or severity were reviewed. Studies in languages other than English were included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: A total of 11 trials were identified concerning the use of azoles in ABPA. Only two prospective controlled trials were identified. The first trial examined the use of Ketoconazole 400 mg daily for 12 months and demonstrated a reduction in immunological markers of disease activity and symptom scores, there was no significant improvement in lung function. The other trial examined the use of itraconazole for 16 weeks. This demonstrated a reduction in corticosteroid usage, an improvement in immunological markers, an improvement in pulmonary function and exercise tolerance. This study was only available as an abstract and limited details were available. REVIEWER'S CONCLUSIONS: There is insufficient information available to recommend the use of azole anti-fungal agents in the routine treatment of patients with ABPA.

Antifungal Agents↗

Manipulation of operant responding for an ethanol-paired conditioned stimulus in the rat by pharmacological alteration of the serotonergic system.

It is becoming increasingly clear that environmental stimuli play a critical role in the maintenance of drug taking behaviour. This has led to investigations into the neural mechanisms by which environmental stimuli can come to control behaviour using paradigms such as conditioned reinforcement. The majority of this work has involved the use of food-paired conditioned stimulus rodent paradigms. Relatively few studies have attempted to investigate the neuropharmacology of behaviour maintained by presentation of a stimulus paired with ethanol drinking. Several lines of research support an important role for brain serotonin (5-HT) neurotransmitter systems in the control of alcohol drinking behaviour. The aim of the present study was, initially, to establish a procedure in which rats respond for an ethanol-paired conditioned stimulus, and second, to study the effects of a range of serotonergic compounds previously shown to be effective in reducing oral ethanol self-administration, on responding for this conditioned stimulus. Results showed that the 5-HT releaser d-fenfluramine, the selective serotonin reuptake inhibitor fluoxetine, the 5-HT1A receptor agonist 8-hydroxy-2[di-n-propylamino]tetralin, the partial 5-HT1A receptor agonist buspirone, and the 5-HT1B/5-HT2C receptor agonist 1-(3-trifluoromethylphenyl)piperazine, but not the 5-HT2A/5-HT2C receptor agonist 1-(2,5-dimethoxy-4-iodophenylaminopropane)-2, selectively reduced responding on a lever leading to presentation of an ethanol paired conditioned stimulus. In addition the non-specific D1/D2 dopamine receptor antagonist haloperidol was active in this paradigm. Results are consistent with involvement of the dopaminergic and 5-HT systems, in particular activation of 5-HT1A and 5-HT1B receptor subtypes, in mediation of the conditioned or secondary reinforcing properties of ethanol.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Can some physical therapy and manual techniques generate potentially osteogenic levels of strain within mammalian bone?

BACKGROUND AND PURPOSE: Although physical therapy techniques are used to alleviate pain and stiffness in joint injuries, whether these methods are capable of affecting bone is unknown. For example, can these techniques potentially influence bone formation or resorption? To begin exploring this possibility, this study investigated the ability of 4 manual techniques to generate levels of compressive strains that presumably can stimulate bone metabolism. SUBJECTS: Six 3,4 metacarpals from three 3-year-old Merino ewes were used. METHODS: A rosette strain gauge was implanted onto the dorsomedial cortex of each ovine 3,4 metacarpal. Four different manual procedures were applied on 2 occasions on each metacarpal in vivo and ex vivo. Mean peak principal compressive strains were calculated for each technique. RESULTS: Levered bending produced greater mean peak compressive strains than almost all other manual procedures tested in vivo or ex vivo. CONCLUSION AND DISCUSSION: Manual levered bending created levels of compressive strain similar in magnitude to those created by mechanical devices used in previous animal experiments to induce new bone formation (osteogenesis). This animal model appears to be suitable for investigating the effects of manually applied procedures on bone and may establish whether manual techniques can stimulate bone formation.

Analysis of Variance↗

Effects of pergolide treatment on in vivo hydroxyl free radical formation during infusion of 6-hydroxydopamine in rat striatum.

This study focused on the early neurochemical events involved in 6-hydroxydopamine (6-OHDA) neurotoxicity and the putative neuroprotective effects of pergolide. 6-OHDA in 0.1% ascorbic acid/saline was delivered into rat striatum by means of microdialysis and 2,3-dihydroxybenzoic acid (2,3-DHBA) was measured as an index of hydroxyl free radical formation using salicylate trapping. Infusion of 6-OHDA (2-20 mM) via the dialysis probe for 15 min was associated with an immediate and striking increase in the extracellular levels of 2,3-DHBA and dopamine, and this effect was dose-dependent. An infusion of 10 mM 6-OHDA, equivalent to a direct injection of approximately 4 microgram free base, resulted in dopamine overflow with a maximum approx. 200-fold above the baseline. This massive overflow of toxic amounts of dopamine, much greater than expected of reuptake inhibition, seems to be the earliest response of nigrostriatal neurones to 6-OHDA. In rats treated with pergolide mesylate (7 days 0.5 mg/kg/day, i.p.), the average amount of 2, 3-DHBA associated with 6-OHDA striatal infusion was significantly smaller than that in controls. This suggests that pergolide treatment leads to an increased ability of striatal tissue to quench hydroxyl radical formation in vivo.

3,4-Dihydroxyphenylacetic Acid↗

An investigation into the effects of 5-HT agonists and receptor antagonists on ethanol self-administration in the rat.

Pharmacological manipulation leading to altered 5-HT function has been widely demonstrated to reduce ethanol intake in free choice tests. The aim of the present study was to examine the effects of a range of compounds known to influence 5-HT neurotransmission, including selective 5-HT receptor agonists and antagonists, on ethanol ingestion and maintained behaviour in an operant self-administration paradigm. Female Sprague-Dawley rats were trained to respond for 8% ethanol (v/v) in a 60-min test by a previously described technique. The number of responses and ethanol reinforcers (dipper deliveries), ethanol consumption (g/kg of body weight), and locomotor activity (LMA) were measured following administration of 5-HT agonists (5-HT, d-fenfluramine, fluoxetine, buspirone, TFMPP, and DOI) and antagonists (metergoline, ritanserin, and ondansetron) 30 min prior to testing. d-Fenfluramine, fluoxetine, buspirone, TFMPP, and DOI all produced a reduction in ethanol ingestion and maintained behaviour at doses that failed to reduce LMA. Conversely, metergoline and ritanserin only reduced ethanol self-administration at doses that concomitantly reduced LMA. 5-HT and ondansetron were without effect on any measure. These results demonstrate that, under the present experimental conditions, activation of central 5-HT1A, 5-HT1B, and 5-HT2 receptors reduced ethanol intake and reinforced behaviour in an operant paradigm.

Animals↗

Strain differences in ethanol preference and reinforced behaviour: a comparison of two-bottle choice and operant self-administration paradigms.

An animal's volitional consumption of ethanol may be influenced by both genetic and environmental factors. In addition, genetic control of ethanol intake may depend on the test paradigm used. In the present study, performance for, and intake of ethanol in a limited access oral operant paradigm, and preference for ethanol in a two-bottle free choice test in the home-cage were compared in female rats of the heterogeneous Sprague Dawley (SD) and inbred Lewis strains. A smaller proportion of SD rats reached criterion on the self-administration task (four of 10 SD vs eight of 10 Lewis), but those SD rats that did achieve criterion maintained higher levels of responding and greater ethanol intake, relative to the Lewis strain, in the operant self-administration paradigm. Additionally, SD but not Lewis rats exhibited increased locomotor activity and an increase in performance for ethanol compared with water. In marked contrast, Lewis rats exhibited a greater preference for 10% ethanol over water in the two-bottle choice test compared with the SD strain, which preferred water to ethanol. These results suggest that both genotype and test paradigm are involved in the extent to which ethanol serves as a positive reinforcer and that unlike two-bottle choice preference tests, self-administration studies are more highly predictive of the reinforcing properties of ethanol.

Alcohol Drinking↗

Vehicle entrapment rescue and pre-hospital trauma care.

From 1 April 1991 to 31 March 1993 the Royal London Hospital Helicopter Emergency Medical Service (HEMS) attended 737 road traffic accidents, 90 (12 per cent) of which involved entrapments. Nine casualties (10 per cent) died, of which five died at the scene. Thirty-two patients with a median ISS 17 (range 1-59) were transported by helicopter to the Royal London Hospital. Of these, four subsequently died in hospital. The median ISS of the non-survivors was 44 (range 24-59). The remaining 53 patients were transported to the nearest hospital. In 45 cases (50 per cent) patient extrication took longer than 30 min. The methods and standards for the release of trapped road traffic accident victims were reviewed to allow physicians a working understanding of Fire Service techniques. Entrapment rescue should create rapid access to the accident victim, allowing stabilization and release with minimum delay. Immediate and uncontrolled release of trapped victims is only indicated if there is immediate danger to life from the surroundings. We recommend a rigorous target of less than 30 min for the release of the casualty. To achieve this will require systematic extrication training for Fire Service crews and medical teams who are involved in immediate care.

Accidents, Traffic↗