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Biomedical subjects

W E Davies

Publications and source records attributed to W E Davies.

At least 19 recordsLinked to original sources
PubMed2000

Taurine fluxes in insulin dependent diabetes mellitus and rehydration in streptozotocin treated rats.

The effect of streptozotocin induced diabetes mellitus and rehydration on brain taurine and brain water content was studied in 4 groups of rats. Two groups of rats with diabetes mellitus were used. In one group, taurine and brain water content were determined following induction of diabetes for one week. In the second group, diabetes was induced for one week but before sacrifice, 15% of body weight of normal saline was introduced into the peritoneum, half at time 0, half 30 minutes later with sacrifice 60 minutes after the first infusion. In two groups of animals (controls), the brain taurine and water content were estimated in normal conditions and after hydration, in exactly the same way as diabetic rats. Brain taurine content was greater in diabetic rats than non-diabetic rats and there was no decrease in brain taurine content within the first hour following rehydration of the diabetic rats. Brain water content was greater in rehydrated diabetic rats than in non-rehydrated diabetic rats but there was no significant change in the brain water content after hydration of non diabetic rats. This suggested that the rapid change in water content of rehydrated diabetic rats was not accompanied by an equally rapid alteration in brain taurine content. This is consistent with the hypothesis that taurine flux could be a major factor in the aetiology of diabetic cerebral oedema. It also allows the development of possible therapeutic options which may increase outward taurine flux from brain cells. Taurine flux is increased by increasing extracellular sodium concentration or decreasing potassium concentration. Phospholemman channels may also influence taurine flux. These may have implications for the optimal method of clinical rehydration undertaken in diabetic ketoacidosis.

Animals↗
PubMed2000

A review of evidence in support of a role for 5-HT in the perception of tinnitus.

Tinnitus is a debilitating condition from which some 0.5-1% of the population of the Western world suffer sufficiently badly as to interfere with their normal working and leisure life. There is no satisfactory treatment at the present time and the uncertainty surrounding the mechanism of its generation makes it difficult to devise an effective cure. After much debate, the consensus of opinion amongst researchers regarding its site of origin is that it is primarily a central nervous system pathology although there certainly exists a class of patients whose tinnitus is peripherally based. In this paper, we provide some speculative ideas on how an initial auditory insult can be translated into central neurological substrates that represent tinnitus. Plastic changes arising from sensory deprivation trigger a change in synaptology and neurotransmission with a consequent change in receptor configuration. From neuroanatomical considerations and analogies with other clinical conditions, we postulate the involvement of serotonin (5-HT) in these plastic changes and consider the evidence available from the use of serotonergic drugs in different conditions. A possible relationship between 5-HT and lidocaine is also discussed.

Animals↗
PubMed1999

Recent advances in the pharmacological treatment of tinnitus.

Tinnitus is an extremely prevalent condition that impinges on the lives of sufferers to varying degrees. In some people, it is a fairly minor irritation but, for many, the tinnitus intrudes to such a degree that it affects their ability to lead a normal life, and in some very extreme cases has resulted in suicide. Insomnia, inability to concentrate and depression are commonly reported to accompany the condition. Relief can be reliably obtained using intravenous lignocaine, which indicates that pharmacology can provide a route for effective alleviation of the condition. In this article, Julie Simpson and Ewart Davies review the potential pharmacological therapies, and emphasize that clinical research has been hampered by the absence of a reliable objective assessment of the tinnitus and by the variable nature of the complaint.

Anti-Anxiety Agents↗
PubMed1999

The assessment of lamotrigine, an antiepileptic drug, in the treatment of tinnitus.

OBJECTIVE: Tinnitus is an extremely prevalent condition that currently has no satisfactory clinical treatment. Development of therapy has been hampered by the diversity of underlying conditions that give rise to the symptom of tinnitus. A drug that has multiple actions may have an improved chance of being effective. One such drug is lamotrigine, a recently developed antiepileptic agent that has both glutamate release inhibition and sodium channel antagonist activity. STUDY DESIGN: Lamotrigine was evaluated in a double-blind, placebo-controlled, crossover clinical trial. Patients initially were tested with an intravenous infusion of lidocaine (10 mg/mL) to a maximum of 100 mg or until a reduction in tinnitus. Lamotrigine or placebo tablets were taken once daily (25 mg) for 2 weeks, 50 mg for 2 weeks, and 100 mg for 4 weeks. SETTING: Patients were chosen from among volunteers from the tinnitus clinic in the local hospital without reference to underlying pathology. PATIENTS: Those patients whose tinnitus had been present for less than 6 months or whose tinnitus was likely to vary spontaneously were excluded. INTERVENTIONS: Perceived intensity and intrusiveness of tinnitus was assessed before entry onto the trial and at 4-week intervals throughout the trial. MAIN OUTCOME MEASURES: Assessment comprised questionnaires, visual analog scales, and a battery of audiologic measurements. RESULTS: There was no correlation between the response to lidocaine and the response to lamotrigine. There was good agreement between the questionnaires and visual analog scales in the reporting of perceived changes; however, this was not reflected as changes in the audiologic tests. CONCLUSIONS: Of the 31 participants who completed the trial, questionnaires indicated that lamotrigine was effective in a very few of these persons.

Anticonvulsants↗
PubMed1998

Effects of dietary taurine on auditory function in full-term infants.

Three groups of neonates fed taurine supplemented infant formula, non-supplemented infant formula or breast milk, respectively, were studied from birth to 12 weeks of age. In addition to the measurement of whole blood taurine content, auditory function was monitored using auditory brainstem responses (ABRs) and transient evoked otoacoustic emissions (TEOAEs). The results showed a significant reduction in whole blood taurine concentration in the non-supplemented formula group. In addition, there was a significant drop in whole blood taurine levels in all 3 groups over the first four weeks of life. ABR wave latencies were significantly shorter in the non-supplemented group, with wave V showing the greatest reductions. Falling taurine levels after full-term birth may aid synaptic maturation/efficiency within the auditory system. TEOAE responses were significantly larger over the low to mid frequencies in the breast fed group suggesting improved middle ear function.

Audiometry, Pure-Tone↗
PubMed1998

Use of homeopathy in the treatment of tinnitus.

Tinnitus is a prevalent condition which has no practical and effective pharmacological treatment. In the absence of relief by conventional routes, sufferers are increasingly turning to 'alternative' or 'complementary' medicine. This paper reports the evaluation of a homeopathic preparation 'Tinnitus' by a double-blind, placebo-controlled clinical trial. The remedy was taken in tablet form at a homeopathic D60 potency. Perceived intensity and intrusiveness of the tinnitus was assessed at four points during the trial by subjective procedures (visual analogue scales and questionnaires) and by a battery of audiological measurements. Although questionnaire responses indicated that the homeopathic preparation was preferred to placebo by 14 of the 28 subjects, an analysis of variance indicated that neither the VAS scores nor the audiological measures showed significant improvement in tinnitus symptoms in response to 'Tinnitus' versus the placebo. It was concluded that 'Tinnitus' could not be shown to be more effective than the matched placebo.

Double-Blind Method↗
PubMed1993

Reduced levels of 5-HT3 receptor recognition sites in the putamen of patients with Huntington's disease.

The present study assessed 5-HT3 receptor recognition site levels in homogenates of putamen derived from patients with clinically and neurochemically diagnosed Huntington's disease or Parkinson's disease and those from age-, sex- and post-mortem delay-matched neurologically and psychiatrically normal patients to investigate the cellular location of 5-HT3 receptors in the human putamen. Specific [3H]granisetron (0.91 nM) binding (defined by ondansetron, 10 microM) was significantly reduced in putamen homogenates from eight out of ten patients with Huntington's disease compared to similar homogenates from 'control' patients (72 +/- 6 and 39 +/- 8 fmol/g wet weight, mean +/- S.E.M., n = 10 and 8, tissue from 'control' and Huntington's disease patients, respectively, P = 0.004). In contrast, specific [3H]granisetron (1.04 nM) binding levels were similar in putamen homogenates from patients with Parkinson's disease when compared to homogenates from 'control' patients. The present results indicate that at least a proportion of the 5-HT3 receptor population in the human putamen is located on neurones that have their cell bodies within this brain region and that these receptors are not primarily located on dopamine neurone terminals in the human putamen.

Dopamine↗
PubMed1993

The effect of nimodipine on salicylate ototoxicity in the rat as revealed by the auditory evoked brain-stem response.

Experiments have been performed to investigate the ototoxic effects of sodium salicylate administration in anaesthetised rats as recorded by the auditory evoked brain-stem response (AEBR). Sodium salicylate (300 mg kg-1 i.p.) produced time-dependent increases in hearing threshold and decreases in the four principle peaks of the AEBR. Maximum responses were obtained at 4 h post-administration and were highly significant (P < 0.001). In a further series of experiments nimodipine, a calcium channel antagonist which has been suggested as a potential therapy for tinnitus, was administered at a dose of 2 mg kg-1 s.c. at the same time as sodium salicylate. This had no effect on the changes in hearing threshold. However, it did reduce the decrease in latencies of three of the four peaks of the AEBR, such that only the decrease in latency of the first peak was significantly different when compared to the pre-injection control latency (P < 0.01). We believe that these findings show specific neurophysiological correlates of salicylate ototoxicity. Since salicylate intoxication is used as the method for inducing tinnitus in animal models, the changes in the AEBR may provide an objective measure by which potential therapeutic intervention may be tested.

Acoustic Stimulation↗
PubMed1993

Cellular localisation of taurine in the organ of Corti.

The cellular localisation of taurine in the organ of Corti has been established using a monoclonal antibody and confocal fluorescence microscopy. The bulk of the taurine was found in the outer hair cells with very little present in the inner hair cells and supporting structures. The outer hair cells which probably function as an amplification/attenuation gain system, control inner hair cell output to the brain. Taurine is tentatively postulated as being related to calcium fluxes involved in outer hair cell response to sound or olivocochlear bundle stimulation. Other possibilities are also discussed.

Acoustic Stimulation↗
PubMed1990

The effect of taurine supplementation on the ototoxicity of neomycin in guinea pigs.

Experiments have been performed to examine the effects of taurine supplementation on the ototoxicity of neomycin. It was found that concurrent administration of taurine and neomycin produced a greater degree of ototoxicity, as evidenced by increases in hearing thresholds, than with neomycin alone. The results are discussed in light of a recently proposed mechanism of aminoglycoside ototoxicity.

Animals↗
PubMed1989

Immobilization hypercalcaemia responding to intravenous pamidronate sodium therapy.

A 16 year old male developed symptomatic hypercalcaemia of immobilization on day 47 following a diving accident which had resulted in incomplete C4 tetraplegia. Following initial reduction in serum calcium with salmon calcitonin 100 U/day, symptomatic hypercalcaemia recurred. A single dose of 30 mg pamidronate sodium, given intravenously, caused serum calcium to fall within 48 hours. Initial mild, asymptomatic hypocalcaemia was followed by a return to sustained normocalcaemia. No major adverse reaction was encountered, and if further clinical experience confirms its efficacy, pamidronate sodium will warrant consideration as first-line therapy for immobilization hypercalcaemia.

Adolescent↗
PubMed1988

A swing to intermittent clean self-catheterisation as a preferred mode of management of the neuropathic bladder for the dextrous spinal cord patient.

Since 1977, 301 patients with spinal cord pathology have been taught to self-catheterize. The majority (234) remain on the programme. The reasons for the 67 ceasing the procedure and the changing pattern of bladder management amongst Queensland's spinally injured community are discussed. The complications and advantages of the system are considered and a plea is put forward that intermittent clean self-catheterisation should be preferred as the preferred option to all spinally injured persons with good hand function.

Adolescent↗
PubMed1988

Tetraplegia resulting from a bus roll over accident: case report.

This is a report on a patient injured when an interstate bus overturned. The mechanism of injury is detailed and the secondary factors that resulted in the injury are discussed. Ways in which similar injuries could be prevented are put forward. An urgent plea is made for a more rational approach to the use of restraint mechanisms for bus passengers.

Accidents, Traffic↗
PubMed1983

The occurrence of gamma-aminobutyrylcholine in mammalian brain-fact or artefact?

gamma-Aminobutyrylcholine (GABAch) has been reported to exist in mammalian brain tissue, but not, as yet, given a specific physiological role in the CNS. In order to investigate further its occurrence and function in the CNS, two new methods have been developed for its isolation and determination at the picomole level. Its isolation has been achieved by ammonium Reineckate precipitation or by cation-exchange followed by HPLC determination of the dansyl and o-phthaldialdehyde derivatives. Using these methods, no free endogenous GABAch (less than 80 pmol/g) was found in rat, guinea pig, cat, pig marmoset, or human brain tissue. No evidence was obtained, either in vitro or in vivo, for the incorporation of [14C]gamma-aminobutyric acid into GABACh. GABACh was hydrolysed at a low rate (maximum of 45 nmol/h/g of brain tissue) after incubation with rat, guinea pig, or cat brain minces and homogenates. These results fail to confirm the data of other investigators, and the possible reasons for this are discussed.

Animals↗
PubMed1982

The absence of substance P from guinea pig auditory structures.

The following auditory structures were examined for Substance-P-Containing cells and fibres using a monoclonal antibody: organ of Corti, spiral ganglion, auditory nerve, cochlear nucleus. No substance P was detected in any of these structures. Giving due consideration to the sensitivity and specificity of this method of detection, it was concluded that Substance P has no function in the lower auditory system of the guinea pig.

Animals↗