Articles: human.
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J Pain Palliat Care Pharmacother · Sep 2014
ReviewTherapeutic challenges in cancer pain management: a systematic review of methadone.
The proven therapeutic efficacy of methadone in cancer pain is hindered by a challenging pharmacokinetic-pharmacodynamic profile, considerable interpatient variation, and increasing concern about the complexities of dosing. The objective of this study was to assess the evidence for the use of methadone in cancer pain management. The authors conducted a systematic literature search for randomized controlled trials (RCTs) published post the 2007 Cochrane review of methadone in cancer pain. ⋯ Methadone has an important role in the management of cancer pain, with many advantages including low cost, high oral bioavailability, rapid onset of action, once-daily dosing, and postulated benefits in difficult pain control scenarios. However, due to limited research in this area, methadone dosing remains a challenge, with vigilant dose initiation, adjustment, and monitoring required. There is a need for further studies using standardized methodology to evaluate the optimal dosing strategy of methadone, the effect on different types of pain, and the role of pharmacokinetics and pharmacogenomics in clinical outcomes.
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Various experimental studies in animals have shown that general anaesthetics are potentially toxic to the developing brain. By inducing apoptosis or interfering with neurogenesis, anaesthetic exposure during a critical period of neuronal development can have significant impact on neurocognitive function later in life. It remains controversial whether these experimental results can be transferred to human beings and this is under intensive scientific evaluation. ⋯ Anaesthesia is not an end in itself, but necessary to facilitate surgical procedures. There is evidence that maintaining physiological conditions is important for the overall outcome following anaesthesia and surgery. Until proven otherwise, it can be recommended to keep anaesthesia and surgery as short as possible, to use short-acting drugs and/or a combination of general anaesthesia and multimodal pain therapy including systemic analgesics, and local or regional anaesthesia, to reduce the overall drug dosage.
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Biological differences in sensory processing between human and model organisms may present significant obstacles to translational approaches in treating chronic pain. To better understand the physiology of human sensory neurons, we performed whole-cell patch-clamp recordings from 141 human dorsal root ganglion (hDRG) neurons from 5 young adult donors without chronic pain. Nearly all small-diameter hDRG neurons (<50 μm) displayed an inflection on the descending slope of the action potential, a defining feature of rodent nociceptive neurons. ⋯ Compared to electrically evoked action potentials, chemically induced action potentials were triggered from less depolarized thresholds and showed distinct afterhyperpolarization kinetics. These data indicate that most small/medium hDRG neurons can be classified as nociceptors, that they respond directly to compounds that produce pain and itch, and that they can be activated and sensitized by inflammatory mediators. The use of hDRG neurons as preclinical vehicles for target validation is discussed.
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Curr Neuropharmacol · Sep 2014
Combination of therapeutic hypothermia and other neuroprotective strategies after an ischemic cerebral insult.
Abrupt deprivation of substrates to neuronal tissue triggers a number of pathological events (the "ischemic cascade") that lead to cell death. As this is a process of delayed neuronal cell death and not an instantaneous event, several pharmacological and non-pharmacological strategies have been developed to attenuate or block this cascade. The most promising neuroprotectant so far is therapeutic hypothermia and its beneficial effects have inspired researchers to further improve its protective benefit by combining it with other neuroprotective agents. ⋯ A distinction is made between drugs interrupting only one event of the ischemic cascade from those mitigating different pathways and having multimodal effects. Also the combination of therapeutic hypothermia with hemicraniectomy, gene therapy and protein therapy is briefly discussed. Furthermore, those combinations that have been studied in a clinical setting are also reviewed.
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A considerable number of deaths due to firearm injuries have occurred during wars all over the world. In this study, it is aimed to evaluate demographic characteristics and injury properties of cases died during civil war in Syria. ⋯ This study indicated that a significant proportion of those who died after being injured in the Syrian war were children, women and elderly people. The nature and localization of the observed injuries indicated open attacks by military forces regardless of targets being civilians and human rights violations.