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.

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.

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.

Neanderthal skeleton from Tabun: U-series data by gamma-ray spectrometry.

The Neanderthal hominid Tabun C1, found in Israel by Garrod & Bate, was attributed to either layer B or C of their stratigraphic sequence. We have used gamma-ray spectrometry to determine the 230Th/234U and 231Pa/235U ratios of two bones from this skeleton, the mandible and a femur. The ages calculated from these ratios depend on the uranium uptake history of the bones. Assuming a model of early U (EU) uptake the age of the Tabun C1 mandible is 34+/-5 ka. The EU age of the femur is 19+/-2 ka. The femur may have experienced continuous (linear) U uptake which would give an age of 33+/-4 ka, in agreement with the mandible's EU age, but implies marked inhomogeneity in U uptake history at the site. These new age estimates for the skeleton suggest that it was younger than deposits of layer C. This apparent age is less than those of other Neanderthals found in Israel, and distinctly younger than the ages of the Skhul and Qafzeh burials. This suggests that Neanderthals did not necessarily coexist with the earliest modern humans in the region. All of the more complete Neanderthal fossils from Israel are now dated to the cool period of the last glacial cycle, suggesting that Neanderthals may have arrived in this region as a result of the southward expansion of their habitable range. The young age determined for the Tabun skeleton would suggest that Neanderthals survived as late in the Levant as they did in Europe.

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.

Australia's oldest human remains: age of the Lake Mungo 3 skeleton.

We have carried out a comprehensive ESR and U-series dating study on the Lake Mungo 3 (LM3) human skeleton. The isotopic Th/U and Pa/U ratios indicate that some minor uranium mobilization may have occurred in the past. Taking such effects into account, the best age estimate for the human skeleton is obtained through the combination of U-series and ESR analyses yielding 62,000+/-6000 years. This age is in close agreement with OSL age estimates on the sediment into which the skeleton was buried of 61,000+/-2000 years. Furthermore, we obtained a U-series age of 81,000+/-21,000 years for the calcitic matrix that was precipitated on the bones after burial. All age results are considerably older than the previously assumed age of LM3 and demonstrate the necessity for directly dating hominid remains. We conclude that the Lake Mungo 3 burial documents the earliest known human presence on the Australian continent. The age implies that people who were skeletally within the range of the present Australian indigenous population colonized the continent during or before oxygen isotope stage 4 (57,000-71,000 years).