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Turkish Journal of Physical Medicine... Sep 2022Hypocalcemia is a rather uncommon condition that may be encountered in the outpatient setting. It may be associated with a wide range of clinical symptoms and signs. It...
Hypocalcemia is a rather uncommon condition that may be encountered in the outpatient setting. It may be associated with a wide range of clinical symptoms and signs. It is unclear that the primary cause of symptom is hypocalcemia, as these symptoms are usually discrete and ambiguous. Signs of muscle cramp and tetany are considered the expressions of overexcitability of peripheral nerves or central nervous system in case of hypocalcemia in the nerve. In this case, we present a 59-year-old female who presented with persistent muscle cramp and pain of both upper and lower extremities and underwent an investigation that revealed electromyographic changes due to hypocalcemia during an electromyographic study.
PubMed: 36475099
DOI: 10.5606/tftrd.2022.8328 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Nov 2022Here, we reported two cases with hyperthyroidism who complained of myalgia and muscle cramps during treatment with methimazole tablets (or Thyrozol, the brand name). One...
Here, we reported two cases with hyperthyroidism who complained of myalgia and muscle cramps during treatment with methimazole tablets (or Thyrozol, the brand name). One case experienced muscle cramps after taking Thyrozol for 6 months, and by this time the patient's thyroid function had returned to normal. In the other case, pain caused by muscular cramps began after the patient took Thyrozol for two weeks and the patient's thyroid function had not returned to normal yet at the time. In both cases, pain caused by muscle cramps appeared while the patients were taking Thyrozol. The myalgia persisted in spite of a reduction in the Thyrozol dose, but was significantly relieved with the discontinuation of Thyrozol. Myalgia and muscle cramps did not recur after the patients were switched to methimazole ointment. There was a strong temporal association between oral administration of Thyrozol and pain caused by muscle cramps, which may indicate that myalgia and muscle cramps are adverse reactions of Thyrozol. Looking into the relevant literature on the topic, we explored in this report the possible mechanisms of the onset of muscle cramps associated with Thyrozol, and compared the adverse reactions of two different formulations of methimazole, intending to provide more clinical experience for the treatment of hyperthyroidism and the management of rare adverse reactions related to antithyroid drugs.
Topics: Humans; Methimazole; Muscle Cramp; Myalgia; Hyperthyroidism; Tablets
PubMed: 36443057
DOI: 10.12182/20221160210 -
Annals of Neurology Mar 2023Isolated dystonia is characterized by abnormal, often painful, postures and repetitive movements due to sustained or intermittent involuntary muscle contractions....
OBJECTIVE
Isolated dystonia is characterized by abnormal, often painful, postures and repetitive movements due to sustained or intermittent involuntary muscle contractions. Botulinum toxin (BoTX) injections into the affected muscles are the first line of therapy. However, there are no objective predictive markers or standardized tests of BoTX efficacy that can be utilized for appropriate candidate selection prior to treatment initiation.
METHODS
We developed a deep learning algorithm, DystoniaBoTXNet, which uses a 3D convolutional neural network architecture and raw structural brain magnetic resonance images (MRIs) to automatically discover and test a neural network biomarker of BoTX efficacy in 284 patients with 4 different forms of focal dystonia, including laryngeal dystonia, blepharospasm, cervical dystonia, and writer's cramp.
RESULTS
DystoniaBoTXNet identified clusters in superior parietal lobule, inferior and middle frontal gyri, middle orbital gyrus, inferior temporal gyrus, corpus callosum, inferior fronto-occipital fasciculus, and anterior thalamic radiation as components of the treatment biomarker. These regions are known to contribute to both dystonia pathophysiology across a broad clinical spectrum of disorder and the central effects of botulinum toxin treatment. Based on its biomarker, DystoniaBoTXNet achieved an overall accuracy of 96.3%, with 100% sensitivity and 86.1% specificity, in predicting BoTX efficacy in patients with isolated dystonia. The algorithmic decision was computed in 19.2 seconds per case.
INTERPRETATION
DystoniaBoTXNet and its treatment biomarker have a high translational potential as an objective, accurate, generalizable, fast, and cost-effective algorithmic platform for enhancing clinical decision making for BoTX treatment in patients with isolated dystonia. ANN NEUROL 2023;93:460-471.
Topics: Humans; Botulinum Toxins; Dystonic Disorders; Blepharospasm; Torticollis; Movement Disorders; Neural Networks, Computer
PubMed: 36440757
DOI: 10.1002/ana.26558 -
Analytical Chemistry Dec 2022The physicochemical properties of active pharmaceutical ingredients (APIs) can depend on their solid-state forms. Therefore, characterization of API forms is crucial for...
The physicochemical properties of active pharmaceutical ingredients (APIs) can depend on their solid-state forms. Therefore, characterization of API forms is crucial for upholding the performance of pharmaceutical products. Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a powerful technique for API quantification due to its selectivity. However, quantitative SSNMR experiments can be time consuming, sometimes requiring days to perform. Sensitivity can be considerably improved using H SSNMR spectroscopy. Nonetheless, quantification via H can be a challenging task due to low spectral resolution. Here, we offer a novel H SSNMR method for rapid API quantification, termed CRAMPS-MAR. The technique is based on combined rotation and multiple-pulse spectroscopy (CRAMPS) and mixture analysis using references (MAR). CRAMPS-MAR can provide high H spectral resolution with standard equipment, and data analysis can be accomplished with ease, even for structurally complex APIs. Using several API species as model systems, we show that CRAMPS-MAR can provide a lower quantitation limit than standard approaches such as fast MAS with peak integration. Furthermore, CRAMPS-MAR was found to be robust for cases that are inapproachable by conventional ultra-fast (i.e., 100 kHz) MAS methods even when state-of-the-art SSNMR equipment was employed. Our results demonstrate CRAMPS-MAR as an alternative quantification technique that can generate new opportunities for analytical research.
Topics: Humans; Muscle Cramp; Magnetic Resonance Spectroscopy; Pharmaceutical Preparations
PubMed: 36417314
DOI: 10.1021/acs.analchem.2c02905 -
Neuromuscular Disorders : NMD Dec 2022Malignant hyperthermia is a life-threatening disorder, which can be prevented by avoiding certain anesthetic agents. Pathogenic variants in the skeletal muscle ryanodine...
Malignant hyperthermia is a life-threatening disorder, which can be prevented by avoiding certain anesthetic agents. Pathogenic variants in the skeletal muscle ryanodine receptor 1-gene are linked to malignant hyperthermia. We retrospectively studied 15 patients who presented to our clinic with symptoms of muscle dysfunction (weakness, myalgia or cramps) and were later found to have a variant in the skeletal muscle ryanodine receptor 1-gene. Symptoms, creatine kinase levels, electromyography, muscle biopsy and in vitro contracture test results were reviewed. Six out of the eleven patients, with a variant of unknown significance in the skeletal muscle ryanodine receptor 1-gene, had a positive in vitro contracture test, indicating malignant hyperthermia susceptibility. In one patient, with two variants of unknown significance, both variants were required to express the malignant hyperthermia-susceptibility trait. Neurologists should consider screening the skeletal muscle ryanodine receptor 1-gene in patients with myalgia or cramps, even when few to no abnormalities on ancillary testing.
Topics: Humans; Contracture; Malignant Hyperthermia; Muscle Contraction; Muscle Cramp; Muscle, Skeletal; Myalgia; Retrospective Studies; Ryanodine; Ryanodine Receptor Calcium Release Channel
PubMed: 36283893
DOI: 10.1016/j.nmd.2022.10.003 -
Medicine Oct 2022Muscle cramps are frequently overlooked and worsen the quality of life in patients with chronic liver disease (CLD). Therefore, a valuable biomarker for predicting...
Muscle cramps are frequently overlooked and worsen the quality of life in patients with chronic liver disease (CLD). Therefore, a valuable biomarker for predicting muscle cramps is required in the clinical setting. This study aimed to investigate whether the serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels, a reliable liver fibrosis marker, could predict muscle cramps in patients with CLD. This retrospective study included 80 patients with CLD. Muscle cramps were assessed using a questionnaire regarding their presence, frequency, pain severity, and duration. The associated predictors were analyzed using logistic regression analysis. The diagnostic accuracy and optimal cutoff values were evaluated using receiver operating characteristic curves. Of the 80 patients, 55% had muscle cramps and showed significantly higher serum M2BPGi levels than those without them (4.54 cutoff index [COI] vs 2.20; P = .001). Multivariate analysis revealed that M2BPGi (odds ratio [ORs], 1.19; 95% confidence interval, 1.003-1.42; P = .046) was independently associated with the presence of muscle cramps. The optimal COI value for predicting muscle cramps was 3.95, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 61.4%, 80.6%, 79.4%, 63.0%, and 70.0%, respectively. Patients with a COI value ≥3.95 had a 2-fold higher incidence of muscle cramps than patients with a COI value <3.95 (79% vs 37%; P < .001). M2BPGi levels were also associated with the duration of muscle cramps. Serum M2BPGi appears useful as a biomarker for predicting muscle cramps in patients with CLD.
Topics: Antigens, Neoplasm; Glycosylation; Humans; Liver Cirrhosis; Membrane Glycoproteins; Muscle Cramp; Quality of Life; Retrospective Studies
PubMed: 36254085
DOI: 10.1097/MD.0000000000031145 -
Trials Oct 2022Neuromuscular electrical stimulation (NMES) is an established therapy that has been widely used for many decades to improve circulation in the legs. However, studies... (Randomized Controlled Trial)
Randomized Controlled Trial
The effect of an 8-week treatment program using a novel foot neuromuscular electrical stimulator on physical function, leg pain, leg symptoms, and leg blood flow in community-dwelling older adults: a randomized sham-controlled trial.
BACKGROUND
Neuromuscular electrical stimulation (NMES) is an established therapy that has been widely used for many decades to improve circulation in the legs. However, studies using NMES devices in an elderly, ambulant, and otherwise apparently healthy population are lacking; this is despite the use of such devices being indicated for lower leg symptoms (such as aches, pain, and cramps) that are frequently seen in older individuals. The main purpose of this study is to evaluate the effect of non-invasive foot NMES (administered using Revitive Medic) on such symptoms compared to a sham in a 12-week period.
METHODS
This is a single-center, single (participant)-blind, parallel-group, randomized, placebo-controlled (sham group), interventional study. Participants will be randomized to 1 of 3 groups (1:1:1) with each study group receiving a different type of foot NMES: Revitive sham; Revitive Medic Program 1; or Revitive Program 2. Each participant will be instructed to self-administer the foot NMES device for 30 min twice daily for 8 weeks. During the study, all participants will continue with their normal life, activities, medications, and diet with no restrictions. Following the 8-week NMES treatment program participants will be assessed for Canadian Occupational Performance Measure performance (COPM-P) and satisfaction (COPM-S) scores, lower leg pain, lower leg symptoms (heaviness, tiredness, aching and cramps), and blood flow volume and intensity.
DISCUSSION
Revitive foot NMES has been proven to increase blood circulation in the legs during use, which may help to relieve symptoms such as pain, heaviness, cramps, and tiredness. When NMES is applied to the plantar surface of the feet it indirectly induces contraction of the calf muscle, activating the musculo-venous pump and thus improving circulation. This study aims to provide data informing on the applicability of foot NMES for the management of leg symptoms that are likely to be indicative of poor circulation in an elderly (> 65 years) community population.
TRIAL REGISTRATION
ISRCTN10576209.
Topics: Aged; Canada; Electric Stimulation Therapy; Humans; Independent Living; Leg; Muscle Cramp; Pain
PubMed: 36242050
DOI: 10.1186/s13063-022-06828-2 -
Journal of Obstetrics and Gynaecology :... Dec 2023Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary...
Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary dysmenorrhoea (PD) development. In this study, a PD rat model was established. The effects of phloroglucinol on the contraction of rat gastric circular muscle and uterine smooth muscle induced by oxytocin (OT) were investigated. The writhing response, and levels of oestradiol (E2), prostaglandin e2 (PGE2), and prostaglandin f2α (PGF2α) were determined. The protein and mRNA levels of OT receptor (OTR) were detected. OT showed a significant promoting effect on gastric circular muscle and uterine smooth muscle contraction. However, phloroglucinol strongly inhibited the contraction induced by 10mol/L of OT. We also found that phloroglucinol reduced writhing response and attenuated uterine damage. Compared to the blank group, E2 and PGF2α were significantly increased, but PGE2 was significantly decreased in the PD model group. Phloroglucinol was found to reverse the changes of E2, PGF2α and PGE2. Moreover, phloroglucinol reduced the protein and mRNA levels of OTR. In conclusion, phloroglucinol could attenuate PD and inhibit the contraction of rat gastric circular muscle and uterine smooth muscle induced by OT. The mechanism might be related with the regulation of OTR expression.IMPACT STATEMENT Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary dysmenorrhoea (PD) development. Phloroglucinol could attenuate PD and inhibit the contraction of rat gastric circular muscle and uterine smooth muscle induced by OT. The underlying mechanisms of phloroglucinol for PD treatment may be associated with OTR. These findings provide novel ideas for the role of phloroglucinol in PD development.
Topics: Female; Humans; Rats; Animals; Oxytocin; Dinoprostone; Dysmenorrhea; Dinoprost; Phloroglucinol; Muscle Cramp; Myometrium; Muscle, Smooth; Stomach; Uterine Contraction; RNA, Messenger
PubMed: 36227618
DOI: 10.1080/01443615.2022.2130208 -
Journal of Cachexia, Sarcopenia and... Dec 2022Cathelicidin, an antimicrobial peptide, plays a key role in regulating bacterial killing and innate immunity; however, its role in skeletal muscle function is unknown....
BACKGROUND
Cathelicidin, an antimicrobial peptide, plays a key role in regulating bacterial killing and innate immunity; however, its role in skeletal muscle function is unknown. We investigated the potential role of cathelicidin in skeletal muscle pathology resulting from acute injury and Duchenne muscular dystrophy (DMD) in mice.
METHODS
Expression changes and muscular localization of mouse cathelicidin-related antimicrobial peptide (Cramp) were examined in the skeletal muscle of normal mice treated with chemicals (cardiotoxin and BaCl ) or in dystrophic muscle of DMD mouse models (mdx, mdx/Utrn and mdx/Utrn ). Cramp penetration into myofibres and effects on muscle damage were studied by treating synthetic peptides to mouse skeletal muscles or C2C12 myotubes. Cramp knockout (KO) mice and mdx/Utrn/Cramp KO lines were used to determine whether Cramp mediates muscle degeneration. Muscle pathophysiology was assessed by histological methods, serum analysis, grip strength and lifespan. Molecular factors targeted by Cramp were identified by the pull-down assay and proteomic analysis.
RESULTS
In response to acute muscle injury, Cramp was activated in muscle-infiltrating neutrophils and internalized into myofibres. Cramp treatments of mouse skeletal muscles or C2C12 myotubes resulted in muscle degeneration and myotube damage, respectively. Genetic ablation of Cramp reduced neutrophil infiltration and ameliorated muscle pathology, such as fibre size (P < 0.001; n = 6) and fibrofatty infiltration (P < 0.05). Genetic reduction of Cramp in mdx/Utrn mice not only attenuated muscle damage (35%, P < 0.05; n = 9-10), myonecrosis (53%, P < 0.05), inflammation (37-65%, P < 0.01) and fibrosis (14%, P < 0.05) but also restored muscle fibre size (14%, P < 0.05) and muscle force (18%, P < 0.05). Reducing Cramp levels led to a 63% (male, P < 0.05; n = 10-14) and a 124% (female, P < 0.001; n = 20) increase in the lifespan of mdx/Utrn mice. Proteomic and mechanistic studies revealed that Cramp cross-talks with Ca signalling in skeletal muscle through sarcoplasmic/endoplasmic reticulum Ca -ATPase1 (SERCA1). Cramp binds and inactivates SERCA1, leading to the activation of Ca -dependent calpain proteases that exacerbate DMD progression.
CONCLUSIONS
These findings identify Cramp as an immune cell-derived regulator of skeletal muscle degeneration and provide a potential therapeutic target for DMD.
Topics: Mice; Male; Female; Animals; Muscular Dystrophy, Duchenne; Mice, Inbred mdx; Proteomics; Muscle, Skeletal; Mice, Knockout
PubMed: 36059045
DOI: 10.1002/jcsm.13065 -
FASEB Journal : Official Publication of... Sep 2022Tree and shrub barks have been used as folk medicine by numerous cultures across the globe for millennia, for a variety of indications, including as vasorelaxants and...
Tree and shrub barks have been used as folk medicine by numerous cultures across the globe for millennia, for a variety of indications, including as vasorelaxants and antispasmodics. Here, using electrophysiology and myography, we discovered that the KCNQ5 voltage-gated potassium channel mediates vascular smooth muscle relaxant effects of barks used in Native American folk medicine. Bark extracts (1%) from Birch, Cramp Bark, Slippery Elm, White Oak, Red Willow, White Willow, and Wild Cherry each strongly activated KCNQ5 expressed in Xenopus oocytes. Testing of a subset including both the most and the least efficacious extracts revealed that Red Willow, White Willow, and White Oak KCNQ-dependently relaxed rat mesenteric arteries; in contrast, Black Haw bark neither activated KCNQ5 nor induced vasorelaxation. Two compounds common to the active barks (gallic acid and tannic acid) had similarly potent and efficacious effects on both KCNQ5 activation and vascular relaxation, and this together with KCNQ5 modulation by other tannins provides a molecular basis for smooth muscle relaxation effects of Native American folk medicine bark extracts.
Topics: Animals; Humans; KCNQ Potassium Channels; Mesenteric Arteries; Rats; Tannins; Vasodilator Agents; American Indian or Alaska Native
PubMed: 35997997
DOI: 10.1096/fj.202200724R