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The development of BVDU: An odyssey.

Brivudin, (()-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) can be considered the gold standard for the treatment of varicella-zoster virus (VZV) infections, such as herpes zoster (shingles). It is available for clinical use in most European countries (except for the UK) and over the whole world (except for the US and Canada). Besides VZV its activity spectrum also includes various other herpesviruses, such as herpes simplex virus type 1 (HSV-1). Its activity against VZV and HSV-1 depends on phosphorylation by the virus-encoded thymidine kinase (TK). In its active form (BVDU TP or BVDU 5'-triphosphate), it can act as both substrate and inhibitor of the viral (i.e., HSV-1) DNA polymerase. It has proven to be effective against herpes zoster, including post-herpetic neuralgia (PHN). It is contra-indicated in patients concomitantly treated by 5-fluorouracil (FU), since its degradation product, ()-5-(2-bromovinyl)uracil, is inhibitory to the catabolism of FU, which may enhance the toxicity of the latter. A new compound, the bicyclic nucleoside analogue (BCNA) Cf-1743, has been described, which is a more potent inhibitor of VZV replication than BVDU and which does not interfere with the catabolism of FU. It is applicable orally, as its 5'-valine ester FV-100 (Fermavir), but has not (yet) been marketed for clinical use.

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Efficacy of Memantine Hydrochloride in Neuropathic Pain.

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Conceptual Model to Illustrate the Symptom Experience and Humanistic Burden Associated With Atopic Dermatitis in Adults and Adolescents.

Atopic dermatitis (AD) is a pruritic or painful dermatologic disease characterized by xerosis and eczema lesions. The symptoms/signs of AD can significantly impact patients' health-related quality of life (HRQoL). This study aimed to qualitatively explore the adult and adolescent experience of AD. A targeted literature review and qualitative concept elicitation interviews with clinicians (n = 5), adult AD patients (n = 28), and adolescent AD patients (n = 20) were conducted to elicit AD signs/symptoms and HRQoL impacts experienced. Verbatim transcripts were analyzed using thematic analysis. Twenty-nine symptoms/signs of AD were reported, including pruritus, pain, erythema, and xerosis. Atopic dermatitis symptoms/signs were reported to substantially impact HRQoL. Scratching was reported to influence the experience of symptoms and HRQoL impacts. Four proximal impacts (including discomfort and sleep disturbance) were reported. Ten domains of distal impact were reported, including impacts on psychological and social functioning and activities of daily living. A conceptual model was developed to summarize these findings. This study highlights the range of symptoms and HRQoL impacts experienced by adults and adolescents with AD. To our knowledge, this study was first to explore the lived experience of AD in both adult and adolescent patients, providing valuable insight into the relatively unexplored adolescent experience of AD.

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Jaw Exercises in the Treatment of Temporomandibular Disorders-An International Modified Delphi Study.

To investigate whether an international consensus exists among TMD experts regarding indications, performance, follow-up, and effectiveness of jaw exercises.

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A Comparative Clinical Study between Clonidine and Tramadol with Bupivacaine in Caudal Epidural for Postoperative Analgesia in Pediatric Surgery.

Adjuvants to bupivacaine for single shot caudal block in children.

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Methanol extract of ameliorates inflammation and nociception in experimental animals.

Methanol extract of (MECN) was evaluated for its anti-inflammatory and analgesic activities using rats and mice. Inflammatory activity of MECN was assessed by carrageenan-induced paw oedema while analgesic activity was evaluated by acetic acid -induced writhing and formalin paw lick test. Histological analyses of the paws were also carried out. There was evaluation of the mechanism(s) of action of MECN using naloxone, a blocker of opioid receptors; atropine, blocker of muscarinic receptors; and propranolol, blocker of beta adrenergic receptors. Findings from the study revealed that MECN has both anti-inflammatory and analgesic properties. These properties were found to be dose dependent with 200 mg/kg of MECN discovered to be the most potent dose. 200 mg/kg was able to cause statistically significant reduction in paw size (p < 0.001) when compared with the carrageenan group. Histological analysis revealed that rats treated with 200 mg/kg of MECN showed no inflammatory cells in the left paw compared to other groups treated with carrageenan. In the formalin test, the number of paw licking was significantly reduced by MECN at 50 mg/kg, 100 mg/kg and 200 mg/kg in both neurogenic and inflammatory pain responses (p < 0.001) even as 200 mg/kg showed the highest percentage inhibition of 98.17% while 100 mg/kg of aspirin showed percentage inhibition of 93.66%. In acetic acid-induced writhing test, 50 mg/kg, 100 mg/kg and 200 mg/kg of MECN produced significant inhibition of writhes when compared with control as highest inhibition is observed in mice that received 200 mg/kg which is similar to aspirin. Administration of propranolol and naloxone was unable to reverse the analgesic function of MECN. However, atropine administration blocked the analgesic function of MECN. This shows that MECN exhibits its analgesic property through cholinergic pathway and not opioid and adrenergic pathways. Phytochemical screening revealed that MECN contains flavonoids, steroids, saponins, tannins, anthraquinines, terpenoids, and alkanoids. These phytochemical contents may thus be responsible for its analgesic and anti-inflammatory properties.

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Does Conservative Temporomandibular Therapy Affect Tinnitus Complaints? A Systematic Review.

To investigate whether temporomandibular disorders treatment can positively influence tinnitus complaints.

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Effect of sustained experimental muscle pain on joint position sense.

Joint position sense (JPS) is impaired in clinical musculoskeletal pain conditions, but when this impairment develops in the transition from initial to prolonged pain is not known.

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The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer.

The advent of neuroimaging methodologies, such as functional magnetic resonance imaging (fMRI), has significantly advanced our understanding of the neurophysiological processes supporting a wide spectrum of mind-body approaches to treat pain. A promising self-regulatory practice, mindfulness meditation, reliably alleviates experimentally induced and clinical pain. Yet, the neural mechanisms supporting mindfulness-based pain relief remain poorly characterized. The present review delineates evidence from a spectrum of fMRI studies showing that the neural mechanisms supporting mindfulness-induced pain attenuation differ across varying levels of meditative experience. After brief mindfulness-based mental training (ie, less than 10 hours of practice), mindfulness-based pain relief is associated with higher order (orbitofrontal cortex and rostral anterior cingulate cortex) regulation of low-level nociceptive neural targets (thalamus and primary somatosensory cortex), suggesting an engagement of unique, reappraisal mechanisms. By contrast, mindfulness-based pain relief after extensive training (greater than 1000 hours of practice) is associated with deactivation of prefrontal and greater activation of somatosensory cortical regions, demonstrating an ability to reduce appraisals of arising sensory events. We also describe recent findings showing that higher levels of dispositional mindfulness, in meditation-naïve individuals, are associated with lower pain and greater deactivation of the posterior cingulate cortex, a neural mechanism implicated in self-referential processes. A brief fMRI primer is presented describing appropriate steps and considerations to conduct studies combining mindfulness, pain, and fMRI. We postulate that the identification of the active analgesic neural substrates involved in mindfulness can be used to inform the development and optimization of behavioral therapies to specifically target pain, an important consideration for the ongoing opioid and chronic pain epidemic.

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[OPIATES IN THE COMPLEX OF ANALGESIA AFTER THORACOTOMY AND ANALYSIS OF THE COMPLICATIONS].

The goal: to study the influence of various methods of analgesia on the state of postoperative anesthesia in patients after thoracotomy; compare the quantity of narcotic analgesics (morphine) used in different types of anesthesia and anesthesia related complications. In 85 patients after thoracotomy, anesthesia was performed by prolonged paravertebral analgesia (PVA) (19 patients), by prolonged epidural analgesia (EDA) (36 patients) with 0.2% solution of rapamycain and by an intravenous patient-controlled analgesia (PCA) with a morphine solution in the control group (30 patients). In all three groups, the nonsteroidal anti-inflammatory drug (NSAIDs) ketorolac tromethamine was used intramuscularly. The evaluation was performed within 3 days after surgery using the visual analog scale (VAS). In the PVA group, the pain level was 29.1 points four hours after surgery to 18.7 points at the end of the third day; in the EDA group – from 24.2 to 20.3 points, respectively; in the control group – from 48.8 to 38.0 points, respectively. The need for morphine administration within the first day after surgery was the highest in the control group and was 42.83±13.23 mg/day. In experimental groups, the need for morphine was 15.0±5.0 mg/day in the EDA group and 16.15±5.38 mg/day in the PVA group. The greatest number of complications was observed in the control group and was associated with the use of morphine. The method of anesthesia associated with the use of PVA was accompanied by the least amount of complications. In terms of the effectiveness of analgesia and the amount of narcotic analgesic used, it was comparable to EDA. Patients of this group least often developed chronic postoperative pain syndrome. PVA may be a priority for postoperative pain management in patients after thoracotomy.

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