291 research outputs found
Late-onset erythromelalgia in a previously healthy young woman: a case report and review of the literature
<p>Abstract</p> <p>Introduction</p> <p>Erythromelalgia is a rare disorder characterized by episodic erythema and burning pain, which commonly involves the extremities. We present a case of late onset erythromelalgia in a previously healthy young woman and briefly review the literature. Our patient's case also has additional uncommon features not reported previously.</p> <p>Case presentation</p> <p>A 33-year-old previously healthy Caucasian woman presented with complaints of episodic burning pain and flushing occurring in a central distribution involving her face, ears, upper chest and, occasionally, her upper extremities. Her symptoms were triggered by lying down or warm temperature exposure and were relieved by cooling measures. Extensive diagnostic work-up looking for secondary causes for the symptoms was negative and the diagnosis of erythromelalgia was made based on details provided in her clinical history supported by raised temperature in the affected area measured by thermography during a symptomatic episode. The patient did not respond to pharmacological therapy or surgical sympathectomy. She was advised on lifestyle modification to avoid activities which triggered her symptoms. She was hypothermic with a core temperature between 92 and 95°F. She also had premature ovarian failure, which had not previously been reported.</p> <p>Conclusion</p> <p>Erythromelalgia is a rare disorder of unknown cause. There is no confirmatory diagnostic test; diagnosis is based on details provided in the patient's medical history and physical examination during the episodes. For those affected, this disorder leads to significant long-term morbidity and unfortunately, to date, no definitive therapy is available except for lifestyle modification.</p
Candidate chemoreceptor subfamilies differentially expressed in the chemosensory organs of the mollusc Aplysia
<p>Abstract</p> <p>Background</p> <p>Marine molluscs, as is the case with most aquatic animals, rely heavily on olfactory cues for survival. In the mollusc <it>Aplysia californica</it>, mate-attraction is mediated by a blend of water-borne protein pheromones that are detected by sensory structures called rhinophores. The expression of G protein and phospholipase C signaling molecules in this organ is consistent with chemosensory detection being via a G-protein-coupled signaling mechanism.</p> <p>Results</p> <p>Here we show that novel multi-transmembrane proteins with similarity to rhodopsin G-protein coupled receptors are expressed in sensory epithelia microdissected from the <it>Aplysia </it>rhinophore. Analysis of the <it>A. californica </it>genome reveals that these are part of larger multigene families that possess features found in metazoan chemosensory receptor families (that is, these families chiefly consist of single exon genes that are clustered in the genome). Phylogenetic analyses show that the novel <it>Aplysia </it>G-protein coupled receptor-like proteins represent three distinct monophyletic subfamilies. Representatives of each subfamily are restricted to or differentially expressed in the rhinophore and oral tentacles, suggesting that they encode functional chemoreceptors and that these olfactory organs sense different chemicals. Those expressed in rhinophores may sense water-borne pheromones. Secondary signaling component proteins Gα<sub>q</sub>, Gα<sub>i</sub>, and Gα<sub>o </sub>are also expressed in the rhinophore sensory epithelium.</p> <p>Conclusion</p> <p>The novel rhodopsin G-protein coupled receptor-like gene subfamilies identified here do not have closely related identifiable orthologs in other metazoans, suggesting that they arose by a lineage-specific expansion as has been observed in chemosensory receptor families in other bilaterians. These candidate chemosensory receptors are expressed and often restricted to rhinophores and oral tentacles, lending support to the notion that water-borne chemical detection in <it>Aplysia </it>involves species- or lineage-specific families of chemosensory receptors.</p
The Future of Biologic Agents in the Treatment of Sjögren’s Syndrome
The gain in knowledge regarding the cellular mechanisms of T and B lymphocyte activity in the pathogenesis of Sjögren’s syndrome (SS) and the current availability of various biological agents (anti-TNF-α, IFN- α, anti-CD20, and anti-CD22) have resulted in new strategies for therapeutic intervention. In SS, various phase I and II studies have been performed to evaluate these new strategies. Currently, B cell-directed therapies seem to be more promising than T cell-related therapies. However, large, randomized, placebo-controlled clinical trials are needed to confirm the promising results of these early studies. When performing these trials, special attention has to be paid to prevent the occasional occurrence of the severe side effects
Familial neuralgia of occipital and intermedius nerves in a Chinese family
Cranial nerve neuralgia usually occurs sporadically. Nonetheless, familial cases of trigeminal neuralgia are not uncommon with a reported incidence of 1–2%, suggestive of an autosomal dominant inheritance. In contrast, familial occipital neuralgia is rarely reported with only one report in the literature. We present a Chinese family with five cases of occipital and nervus intermedius neuralgia alone or in combination in three generations. All persons afflicted with occipital neuralgia have suffered from paroxysmal ‘electric wave’-like pain for years. In the first generation, the father (index patient) was affected, in the second generation all his three daughters (with two sons spared) and in the third generation a daughter’s male offspring is affected. This familial pattern suggests an X-linked dominant or an autosomal dominant inheritance mode
Spatial and Temporal Variability of Macroinvertebrates in Spawning and Non-Spawning Habitats during a Salmon Run in Southeast Alaska
Spawning salmon create patches of disturbance through redd digging which can reduce macroinvertebrate abundance and biomass in spawning habitat. We asked whether displaced invertebrates use non-spawning habitats as refugia in streams. Our study explored how the spatial and temporal distribution of macroinvertebrates changed during a pink salmon (Oncorhynchus gorbuscha) spawning run and compared macroinvertebrates in spawning (riffle) and non-spawning (refugia) habitats in an Alaskan stream. Potential refugia included: pools, stream margins and the hyporheic zone, and we also sampled invertebrate drift. We predicted that macroinvertebrates would decline in riffles and increase in drift and refugia habitats during salmon spawning. We observed a reduction in the density, biomass and taxonomic richness of macroinvertebrates in riffles during spawning. There was no change in pool and margin invertebrate communities, except insect biomass declined in pools during the spawning period. Macroinvertebrate density was greater in the hyporheic zone and macroinvertebrate density and richness increased in the drift during spawning. We observed significant invertebrate declines within spawning habitat; however in non-spawning habitat, there were less pronounced changes in invertebrate density and richness. The results observed may be due to spawning-related disturbances, insect phenology, or other variables. We propose that certain in-stream habitats could be important for the persistence of macroinvertebrates during salmon spawning in a Southeast Alaskan stream
Antisense-Mediated Knockdown of NaV1.8, but Not NaV1.9, Generates Inhibitory Effects on Complete Freund's Adjuvant-Induced Inflammatory Pain in Rat
Tetrodotoxin-resistant (TTX-R) sodium channels NaV1.8 and NaV1.9 in sensory neurons were known as key pain modulators. Comparing with the widely reported NaV1.8, roles of NaV1.9 on inflammatory pain are poorly studied by antisense-induced specific gene knockdown. Here, we used molecular, electrophysiological and behavioral methods to examine the effects of antisense oligodeoxynucleotide (AS ODN) targeting NaV1.8 and NaV1.9 on inflammatory pain. Following complete Freund's adjuvant (CFA) inflammation treatment, NaV1.8 and NaV1.9 in rat dorsal root ganglion (DRG) up-regulated mRNA and protein expressions and increased sodium current densities. Immunohistochemical data demonstrated that NaV1.8 mainly localized in medium and small-sized DRG neurons, whereas NaV1.9 only expressed in small-sized DRG neurons. Intrathecal (i.t.) delivery of AS ODN was used to down-regulate NaV1.8 or NaV1.9 expressions confirmed by immunohistochemistry and western blot. Unexpectedly, behavioral tests showed that only NaV1.8 AS ODN, but not NaV1.9 AS ODN could reverse CFA-induced heat and mechanical hypersensitivity. Our data indicated that TTX-R sodium channels NaV1.8 and NaV1.9 in primary sensory neurons played distinct roles in CFA-induced inflammatory pain and suggested that antisense oligodeoxynucleotide-mediated blocking of key pain modulator might point toward a potential treatment strategy against certain types of inflammatory pain
Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels
Chronic pain is a global problem affecting up to 20% of the world’s population and has a significant economic, social and personal cost to society. Sensory neurons of the dorsal root ganglia (DRG) detect noxious stimuli and transmit this sensory information to regions of the central nervous system (CNS) where activity is perceived as pain. DRG neurons express multiple voltage-gated sodium channels that underlie their excitability. Research over the last 20 years has provided valuable insights into the critical roles that two channels, NaV1.7 and NaV1.9, play in pain signalling in man. Gain of function mutations in NaV1.7 cause painful conditions while loss of function mutations cause complete insensitivity to pain. Only gain of function mutations have been reported for NaV1.9. However, while most NaV1.9 mutations lead to painful conditions, a few are reported to cause insensitivity to pain. The critical roles these channels play in pain along with their low expression in the CNS and heart muscle suggest they are valid targets for novel analgesic drugs
Sodium channel slow inactivation interferes with open channel block
Mutations in the voltage-gated sodium channel Nav1.7 are linked to inherited pain syndromes such as erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). PEPD mutations impair Nav1.7 fast inactivation and increase persistent currents. PEPD mutations also increase resurgent currents, which involve the voltage-dependent release of an open channel blocker. In contrast, IEM mutations, whenever tested, leave resurgent currents unchanged. Accordingly, the IEM deletion mutation L955 (ΔL955) fails to produce resurgent currents despite enhanced persistent currents, which have hitherto been considered a prerequisite for resurgent currents. Additionally, ΔL955 exhibits a prominent enhancement of slow inactivation (SI). We introduced mutations into Nav1.7 and Nav1.6 that either enhance or impair SI in order to investigate their effects on resurgent currents. Our results show that enhanced SI is accompanied by impaired resurgent currents, which suggests that SI may interfere with open-channel block
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A review on approaches to solving Poisson’s equation in projection-based meshless methods for modelling strongly nonlinear water waves
Three meshless methods, including incompressible smooth particle hydrodynamic (ISPH), moving particle semi-implicit (MPS) and meshless local Petrov–Galerkin method based on Rankine source solution (MLPG_R) methods, are often employed to model nonlinear or violent water waves and their interaction with marine structures. They are all based on the projection procedure, in which solving Poisson’s equation about pressure at each time step is a major task. There are three different approaches to solving Poisson’s equation, i.e. (1) discretizing Laplacian directly by approximating the second-order derivatives, (2) transferring Poisson’s equation into a weak form containing only gradient of pressure and (3) transferring Poisson’s equation into a weak form that does not contain any derivatives of functions to be solved. The first approach is often adopted in ISPH and MPS, while the third one is implemented by the MLPG_R method. This paper attempts to review the most popular, though not all, approaches available in literature for solving the equation
High prevalence of shoulder girdle muscles with myofascial trigger points in patients with shoulder pain
Background: Shoulder pain is reported to be highly prevalent and tends to be recurrent or persistent despite medical treatment. The pathophysiological mechanisms of shoulder pain are poorly understood. Furthermore, there is little evidence supporting the effectiveness of current treatment protocols. Although myofascial trigger points (MTrPs) are rarely mentioned in relation to shoulder pain, they may present an alternative underlying mechanism, which would provide new treatment targets through MTrP inactivation. While previous research has demonstrated that trained physiotherapists can reliably identify MTrPs in patients with shoulder pain, the percentage of patients who actually have MTrPs remains unclear. The aim of this observational study was to assess the prevalence of muscles with MTrPs and the association between MTrPs and the severity of pain and functioning in patients with chronic non-traumatic unilateral shoulder pain. Methods: An observational study was conducted. Subjects were recruited from patients participating in a controlled trial studying the effectiveness of physical therapy on patients with unilateral non-traumatic shoulder pain. Sociodemographic and patient-reported symptom scores, including the Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire, and Visual Analogue Scales for Pain were compared with other studies. To test for differences in age, gender distribution, and education level between the current study population and the populations from Dutch shoulder studies, the one sample T-test was used. One observer examined all subjects (n = 72) for the presence of MTrPs. Frequency distributions, means, medians, standard deviations, and 95% confidence intervals were calculated for descriptive purposes. The Spearman's rank-order correlation (rho) was used to test for association between variables. Results: MTrPs were identified in all subjects. The median number of muscles with MTrPs per subject was 6 (active MTrPs) and 4 (latent MTrPs). Active MTrPs were most prevalent in the infraspinatus (77%) and the upper trapezius muscles (58%), whereas latent MTrPs were most prevalent in the teres major (49%) and anterior deltoid muscles (38%). The number of muscles with active MTrPs was only moderately correlated with the DASH score. Conclusion: The prevalence of muscles containing active and latent MTrPs in a sample of patients with chronic non-traumatic shoulder pain was high
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