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Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.
The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.
[Gas embolism and flexible Ecoflac type bag].
Gas embolism at the end of infusion is a well known hazard, that should have disappeared with the use of flexible bags. However, some cases have been reported after pressure infusion. This experimental study evaluates the risk for gas embolism with Ecoflac type flexible bags. These bags are safe under normal pressure infusion conditions with a pneumatic sleeve, because of their texture and pliability; indeed, only minimal air volumes could be expelled, without any risk even in children. However, to be on the safe side, the manufacturer recommends to expel any residual air before pressure administration. This recommendation applies to any bag containing residual air, and since many people are not aware of this, it is rarely put into practice.
Treatment of idiopathic trigeminal neuralgia: comparison of long-term outcome after radiofrequency rhizotomy and microvascular decompression.
OBJECTIVE: To evaluate the long-term outcome of patients after either percutaneous trigeminal rhizotomy or microvascular decompression (MVD) for idiopathic trigeminal neuralgia at a single institution. METHODS: From 1977 to 1997, 316 radiofrequency lesion procedures and 378 MVDs were performed. Questionnaires were sent to all patients who were alive in 1981, 1982, 1992, and 1998. For all other patients, interviews were conducted with their relatives and general practitioners. A retrospective comparative analysis was performed with Kaplan-Meier probability curves as of the latest follow-up date. In addition, 80 patients who underwent MVD were examined postoperatively with quantitative sensory measurements by use of von Frey hairs. RESULTS: Two hundred twenty-five patients who underwent MVD and 206 patients who underwent radiofrequency could be analyzed retrospectively in detail. Overall, there was a 50% risk for recurrence of pain 2 years after percutaneous radiofrequency rhizotomy. Conversely, 64% of patients who underwent MVD remained completely pain free 20 years postoperatively. Patients without sensory impairment after MVD were pain free significantly longer than patients who experienced postoperative hypesthesia or partial rhizotomy. CONCLUSION: Because it is curative and nondestructive, MVD is considered the treatment of choice for trigeminal neuralgia in otherwise healthy people. In our study, it proved to be a more effective and long-lasting procedure for patients with typical trigeminal neuralgia than radiofrequency rhizotomy. Patients without postoperative sensory deficit remained pain free significantly longer, which is a strong argument against the "trauma" hypothesis of this procedure.
[Use of opioids in the elderly -- pharmacokinetic and pharmacodynamic considerations].
Perioperative management of geriatric patients is becoming an important component in anaesthetic practice in the 21st century. This phenomenon is due to the fact that people aged 65 and over are the segment with the fastest growing population. Thus, it is estimated that by the year 2025 20 % of the population in the western hemisphere will be > 65 years of age. Currently, elderly patients comprise one-third of all operations, and one out of two patients older than 65 years of age will undergo an operation in their lifetime. The dramatic change in demographics of surgical patients will have a tremendous impact on the use of anaesthetics. Older patients facing surgery can generally be expected to be a more complex case than their younger counterparts. They have more systemic diseases (e. g. cardiac, pulmonary, endocrine), and usually these diseases have advanced to more serious stages. These patients may suffer disability, both physical and mental, and may show differences in the pharmacokinetic as well as the pharmacodynamic of compounds such as opioids. While neuronal numbers, dendrites and synapses decline with age and the ventricular volume triples, cerebral circulation is similar to young adults, although there is a reduction in cerebral blood flow (CBF). This is because of the lower unit weight, lower CBF and CMRO (2), which are tightly coupled in aging where autoregulation is preserved. However, because of a decline in dopaminergic, serotonergic, cholinergic and GABAergic transmitters, anticholinergic compounds (atropine, scopolamine) as well as some anaesthetics such as ketamine, benzodiazepines or even propofol may produce delirium and/or an increase in efficacy when given together with opioids. Therefore it is mandatory to consider a pharmacologic interaction with a potentiation and/or an addition in effects of other drugs when judging the net action of opioids in the elderly. Physicians and nurses treating geriatric patients tend to have an unfounded level of fear of complications associated with treating perioperative pain. Although it is known that inadequate analgesia may delay recovery, the treatment of perioperative pain in the geriatric patient remains inadequate, even relative to younger patients. It is well established that there is increased responsiveness to the effects of opioids in the elderly. This may result in an increased risk of respiratory depression, while especially the elderly female patient demonstrates an increase in the duration of effects, but the risk of nausea is not augmented. Increased sensitivity of older patients to systemic opioids mostly involves pharmacokinetic factors such as a higher proportion of unbound and active substances as well as changes in drug redistribution. Because of a 40 % reduction in stroke volume in the elderly, there is a protracted redistribution of opioids to the liver. This results in a prolonged metabolisation, a lesser inactivation over time followed by an increase in duration of effects, mainly impairment of respiration. To a much lesser extent, pharmacodynamic factors with an increased response at opioid receptor sites have to be considered. Although the mechanisms causing differences of opioid action in the elderly may be complex, the clinical implications are not. They include slow titration of opioids to allow for long circulation times, lower total doses because of increased sensitivity, and anticipation of a longer duration of action because of reduced clearance. Since elderly patients present multimorbidity, therapy of chronic pain has to be considered in the light of multidrug intake, which, due to interaction, results in marked side-effects, and a prolonged duration of action. Those opioids should be used which, due to their pharmacokinetic properties, have a reduced volume of distribution, present a low plasma protein binding and finally result in the formation of no pharmacologically active metabolites.