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Pharmacological inhibition of the NLRP3 inflammasome as a potential target for cancer-induced bone pain.

Cancer-induced bone pain (CIBP) remains a major challenge in patients suffering from bone metastases because of the complex mechanisms and unsatisfactory treatments. Emerging evidence have shown that activation of inflammasomes contribute to the development of inflammatory and neuropathic pain. However, the role of spinal inflammasomes in CIBP remains unclear. In the present study, we explored the specific cellular mechanisms of NLRP3 inflammasome in the process of CIBP in rats. MCC950 is a small molecule inhibitor of the NLRP3 inflammasome that exhibits remarkable activity in inflammatory diseases. Our behavioral results confirmed that both single and persistent treatment with MCC950 markedly attenuated CIBP-related mechanical allodynia. The expression of NLRP3 inflammasome, including NLRP3, ASC, Caspase-1, were significantly increased in a time-dependent manner. Furthermore, spinal IL-1β, cleaved by cysteine-aspartic acid protease, was upregulated in this study. Chronic administration with MCC950 restored the protein expression of NLRP3 inflammasome and significantly suppressed the upregulation of IL-1β. Spinal NLRP3 inflammasome might be a novel therapeutic target for treatment of CIBP.

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Opioid- and Motor-sparing with Proximal, Mid-, and Distal Locations for Adductor Canal Block in Anterior Cruciate Ligament Reconstruction: A Randomized Clinical Trial.

Adductor canal nerve block is useful for a range of knee surgeries, although the optimal injection location has not been definedUnfortunately, analgesia achieved using adductor canal block is sometimes accompanied by unwanted motor block WHAT THIS ARTICLE TELLS US THAT IS NEW: Proximal adductor canal injections were associated with lower first 24-h morphine consumption than when injections were more distalDecreases in quadriceps strength were similar whether the injection was made in a proximal, mid-, or distal adductor canal location BACKGROUND:: The ideal location for single-injection adductor canal block that maximizes analgesia while minimizing quadriceps weakness after painful knee surgery is unclear. This triple-blind trial compares ultrasound-guided adductor canal block injection locations with the femoral artery positioned medial (proximal adductor canal), inferior (mid-adductor canal), and lateral (distal adductor canal) to the sartorius muscle to determine the location that optimizes postoperative analgesia and motor function. The hypothesis was that distal adductor block has (1) a superior opioid-sparing effect and (2) preserved quadriceps strength, compared with proximal and mid-locations for anterior cruciate ligament reconstruction.

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Characterization of microvascular disease in patients with sickle cell disease using nailfold capillaroscopy.

Sickle cell disease (SCD) is a disorder characterized by repetitive vaso-occlusive crises causing microvascular obstruction, tissue ischemia and pain that may lead to chronic multi-organ ischemic sequelae. Nailfold videocapillaroscopy (NFC) is a non-invasive imaging technique used in clinical rheumatology to directly visualize capillaries located near the fingertip. To characterize NFC abnormalities in the setting of SCD, we performed NFC on 71 SCD patients and 70 age matched controls using a video capillaroscope on 8 digits. As compared to controls, mean capillary number was lower and the final capillary score (measure of capillary dropout inversely related to capillary density) was higher in the SCD group. The SCD group had a lower percentage of stereotype hairpin shapes and a higher percentage of crossing type capillaries. On multivariate linear analyses, both mean capillary number and final capillary score were independently associated with SCD after adjusting for age, body mass index, and gender. SCD was associated with more dilated capillaries but similar numbers of hemorrhages. In conclusion, SCD is associated with lower capillary density and more dilated capillaries on NFC. These changes appear unrelated to markers of disease severity including frequency of sickle crises, number of transfusions, and HbS levels. The relation between NFC and target organ involvement merits further study.

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Use of Midazolam for Minimal Sedation in Pediatric Outpatients: A Survey Analysis of Patient Experience and Parent-Guardian Satisfaction.

Use of procedural sedation to promote anxiolysis, analgesia, and amnesia enhances both pediatric patient experience and procedural outcomes. Sanford Children's outpatient sedation clinic currently uses oral midazolam for minimal sedation.

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“Sinus Headache”: Diagnosis and Dilemma?? An Analytical and Prospective Study.

To evaluate the type, location, severity of headache and their relation to various nasal and sinus related pathological conditions. All the patients presenting with acute and chronic sinus and nasal infections along with headache were included in the study. The diagnostic confirmation was done with clinical along with radiological and endoscopic evaluation. Various parameters categorized accordingly. Chronic rhinosinusitis/chronic recurrent rhinosinusitis are the most common nasal condition seen in oto-rhino-laryngology OPD which has enormous economic burden and significant morbidity on general population. The headache is the commonest associated symptom which is needed to be given attention. The location, variation, pattern of the headache can guide us towards the correct diagnosis.

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Effectiveness of the traditional Japanese Kampo medicine Yokukansan for chronic migraine: A case report.

The traditional Japanese Kampo medicine Yokukansan (TSUMURA Yokukansan extract granules) was originally used to treat neurosis, insomnia, night crying, and irritability and/or agitation in infants and recently it has also been used for neuropsychiatric symptoms in Alzheimer's disease or other dementia in Japan. Furthermore, several recent studies have reported the efficacy of Kampo medicines for various types of headache. Here, we report a case of severe chronic migraine refractory to prophylactic therapy using various western medicines and Japanese Kampo medicines that had resulted in a leave of absence from work, but for which the frequency and severity were markedly decreased by Yokukansan (2.5 g 3 times/d), enabling the patient to return to work fully.

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[Erratum to: Therapy of herpes zoster and postherpetic neuralgia].

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Fructose malabsorption in asymptomatic children and in patients with functional chronic abdominal pain: a prospective comparative study.

The objective of this prospective cohort study was to compare fructose malabsorption in patients with functional chronic abdominal pain and in healthy children. The sample was divided into two groups: asymptomatic children and pain-predominant functional gastrointestinal disorders according to the Rome IV criteria. All children were tested for fructose malabsorption by a standardized breath hydrogen test. Hydrogen and methane were measured and the test was presumed positive when it exceeded 20 ppm above baseline. If positive, patients were given a low-fructose diet and the response was evaluated. One hundred five children were included (34 healthy children, 71 with functional chronic abdominal pain), with similar demographic characteristics in both groups (35.2% male, age 9.5 ± 2.8 years). Hydrogen levels in breath were tested through a hydrogen test for fructose demonstrating malabsorption in 58.8% of healthy children (95%CI 40.8%-76.8%) and in 40.8% of children with chronic abdominal pain (95%CI 28.7%-53.0%), removing those who had bacterial overgrowth. Twenty-one of 31 patients with symptoms and a positive test (72.4%) reported an improvement on a low-fructose diet.Conclusion: Fructose malabsorption is more common in asymptomatic children than in patients with chronic abdominal pain. Better standardized test conditions are necessary to improve accuracy of diagnosis before using this test in clinical practice. What is Known: • Although fructose malabsorption is believed to be related with chronic abdominal pain, high-quality evidence is lacking. • Concerns have raised regarding the use of breath hydrogen test for fructose malabsorption in children with chronic abdominal pain. What is New: • Fructose malabsorption is not more common in children with pain-predominant functional gastrointestinal disorders than in asymptomatic children. • Improvement in symptoms with low-fructose diet may indicate that, although patients with pain-predominant functional gastrointestinal disorders did not have a higher percentage of malabsorption, they had greater fructose intolerance.

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Peripheral nerve catheters: A critical review of the efficacy.

Continuous peripheral nerve blocks are commonly used for postoperative analgesia after surgery. However, catheter failure may occur due to either primary (incorrect insertion) or secondary reasons (displacement, obstruction, disconnection). Catheter failure results in unanticipated pain, need for opioid use, and risk of readmission or delay in hospital discharge. This review aimed to assess definition and frequency of catheter failure, and discuss the alternatives to prolong duration of single-shot nerve blocks. A literature search was performed on peripheral catheters reporting failure as the main outcome measure. Thirty-three studies met the selection criteria, comprising 2711 catheters. Literature review suggests that peripheral nerve catheters have clinically significant failure rate when the assessment is performed using an objective (imaging) method. Subjective methods of assessment (without imaging) may underestimate the incidence of catheter failure.

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Proximal Plantar Intrinsic Tendinopathy: Anatomical and Biomechanical Considerations in Plantar Heel Pain.

Plantar heel pain is often managed through podiatric and physical therapy interventions. Numerous differential diagnoses may be implicated in patients presenting with plantar heel pain; however, symptoms are often attributed to plantar fasciitis. Abductor hallucis, flexor digitorum brevis, and quadratus plantae share proximal anatomic attachment sites and mechanical function with the plantar fascia. Although these plantar intrinsic muscles each perform isolated digital actions based on fiber orientation and attachment sites, they function collectively to resist depression of the lateral and medial longitudinal arches of the foot. Overuse injury is the primary contributing factor in tendinopathy. The close anatomic proximity and mechanical function of these muscles relative to the plantar fascia suggests potential for proximal plantar intrinsic tendinopathy as a result of repetitive loading during gait and other weightbearing activities. To date, this diagnosis has not been proposed in the scientific literature. Future studies should seek to confirm or refute the existence of proximal plantar intrinsic tendinopathic changes in patients with acute and chronic plantar heel pain through diagnostic imaging studies, analysis of lactate concentration in pathologic versus nonpathologic tendons, and response to specific podiatric and physical therapy interventions germane to tendinopathy of these muscles.

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