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Esophagogastric junction morphology and contractile integral on high-resolution manometry in asymptomatic healthy volunteers: An international multicenter study

Rogers BD, Rengarajan A, Abrahao L, Bhatia S, Bor S, Carlson DA, et al.

Neurogastroenterol Motil, 2021 06;33(6):e14009.
PMID: 33094875 DOI: 10.1111/nmo.14009

BACKGROUND: Esophagogastric junction contractile integral (EGJ-CI) and EGJ morphology are high-resolution manometry (HRM) metrics that assess EGJ barrier function. Normative data standardized across world regions and HRM manufacturers are limited.
METHODS: Our aim was to determine normative EGJ metrics in a large international cohort of healthy volunteers undergoing HRM (Medtronic, Laborie, and Diversatek software) acquired from 16 countries in four world regions. EGJ-CI was calculated by the same two investigators using a distal contractile integral-like measurement across the EGJ for three respiratory cycles and corrected for respiration (mm Hg cm), using manufacturer-specific software tools. EGJ morphology was designated according to Chicago Classification v3.0. Median EGJ-CI values were calculated across age, genders, HRM systems, and regions.
RESULTS: Of 484 studies (28.0 years, 56.2% F, 60.7% Medtronic studies, 26.0% Laborie, and 13.2% Diversatek), EGJ morphology was type 1 in 97.1%. Median EGJ-CI was similar between Medtronic (37.0 mm Hg cm, IQR 23.6-53.7 mm Hg cm) and Diversatek (34.9 mm Hg cm, IQR 22.1-56.1 mm Hg cm, P = 0.87), but was significantly higher using Laborie equipment (56.5 mm Hg cm, IQR 35.0-75.3 mm Hg cm, P

Matched MeSH terms: Muscle Contraction/physiology
The Association Between Levator-Urethra Gap Measurements and Symptoms and Signs of Female Pelvic Organ Prolapse

Kamisan Atan I, Shek KL, Furtado GI, Caudwell-Hall J, Dietz HP

Female Pelvic Med Reconstr Surg, 2016 Nov-Dec;22(6):442-446.
PMID: 27465815

OBJECTIVES: Levator avulsion is associated with pelvic organ prolapse in women. It is diagnosed clinically by a widened gap on palpation between the insertion of the puborectalis muscle on the inferior pubic ramus and the urethra. This gap can also be assessed on imaging. This study aimed to determine the association between sonographically determined levator-urethral gap (LUG) measurements and symptoms and signs of prolapse.

METHODS: This is a retrospective study on 450 women seen in a tertiary urogynecological center for symptoms of pelvic floor dysfunction between January 2013 and February 2014. All had a standardized interview, International Continence Society Pelvic Organ Prolapse Quantification assessment and 4-dimensional translabial ultrasound. Post-imaging analysis of archived ultrasound volumes for LUG measurement was undertaken on tomographic slices at the plane of minimal hiatal dimensions and within 5-mm cranial to this plane, bilaterally at an interslice interval of 2.5 mm, blinded against all clinical data. A LUG of 25 mm or greater was considered abnormal.

RESULTS: Mean LUG and maximum LUG in individuals were 22.5 mm (SD, 4.6) and 26.4 mm (SD, 6.0), respectively, with at least 1 abnormal LUG in 51% (n = 222). An abnormal LUG in all 3 slices involving the plane of minimal hiatal dimensions and within 5 mm cranial to this plane on at least 1 side was fulfilled in 24% (n = 103). The LUG measurements were strongly associated with bother, symptoms and signs of prolapse (P < 0.001 to 0.002). This remained significant on multivariate analysis controlling for potential confounding factors.

CONCLUSIONS: Sonographically determined LUG is strongly associated with symptoms, symptom bother, and pelvic organ prolapse on clinical examination and imaging.

Matched MeSH terms: Muscle Contraction/physiology
Differential Effects of 7 and 16 Groups of Muscle Relaxation Training Following Repeated Submaximal Intensity Exercise in Young Football Players

Sharifah Maimunah SM, Hashim HA

Percept Mot Skills, 2016 Feb;122(1):227-37.
PMID: 27420318 DOI: 10.1177/0031512515625383

This study compares two versions of progressive muscle relaxation (PMR) training (7 and 16 muscle groups) on oxygen consumption (VO2), heart rates, rating of perceived exertion and choice reaction time. Football (soccer) players (N = 26; M age = 13.4 yr., SD = 0.5) were randomly assigned to either 7 muscle groups PMR, 16 muscle groups PMR, or a control group. PMR training requires the participants to tense a muscle, hold the muscle contraction, and then relax it. Measurement was conducted prior to and after the completion of 12 sessions of PMR. The dependent variables were measured following four bouts of intermittent exercise consisting of 12 min. of running at 60% VO2max for 10 min. followed by running at 90% VO2max for 2 min. with a 3-min. rest for each bout. Lower VO2, heart rate, perceived exertion, and quicker reaction time were expected in both relaxation groups compared to the control group. The results revealed a significant reduction in heart rates and choice reaction time for both relaxation groups, but the longer version produced significantly quicker choice reaction time.

Matched MeSH terms: Muscle Contraction/physiology
Electrical stimulation-evoked contractions blunt orthostatic hypotension in sub-acute spinal cord-injured individuals: two clinical case studies

Hamzaid NA, Tean LT, Davis GM, Suhaimi A, Hasnan N

Spinal Cord, 2015 May;53(5):375-9.
PMID: 25366533 DOI: 10.1038/sc.2014.187

STUDY DESIGN: Prospective study of two cases.
OBJECTIVES: To describe the effects of electrical stimulation (ES) therapy in the 4-week management of two sub-acute spinal cord-injured (SCI) individuals (C7 American Spinal Injury Association Impairment Scale (AIS) B and T9 AIS (B)).
SETTING: University Malaya Medical Centre, Kuala Lumpur, Malaysia.
METHODS: A diagnostic tilt-table test was conducted to confirm the presence of orthostatic hypotension (OH) based on the current clinical definitions. Following initial assessment, subjects underwent 4 weeks of ES therapy 4 times weekly for 1 h per day. Post-tests tilt table challenge, both with and without ES on their rectus abdominis, quadriceps, hamstrings and gastrocnemius muscles, was conducted at the end of the study (week 5). Subjects' blood pressures (BP) and heart rates (HR) were recorded every minute during pre-test and post-tests. Orthostatic symptoms, as well as the maximum tolerance time that the subjects could withstand head up tilt at 60°, were recorded.
RESULTS: Subject A improved his orthostatic symptoms, but did not recover from clinically defined OH based on the 20-min duration requirement. With concurrent ES therapy, 60° head up tilt BP was 89/62 mm Hg compared with baseline BP of 115/71 mm Hg. Subject B fully recovered from OH demonstrated by BP of 105/71 mm Hg during the 60° head up tilt compared with baseline BP of 124/77 mm Hg. Both patients demonstrated longer tolerance time during head up tilt with concomitant ES (subject A: pre-test 4 min, post-test without ES 6 min, post-test with ES 12 min; subject B: pre-test 4 min, post-test without ES 28 min, post-test with ES 60 min).
CONCLUSIONS: Weekly ES therapy had positive effect on OH management in sub-acute SCI individuals.

Matched MeSH terms: Muscle Contraction/physiology*
The association between different measures of pelvic floor muscle function and female pelvic organ prolapse

Oversand SH, Atan IK, Shek KL, Dietz HP

Int Urogynecol J, 2015 Dec;26(12):1777-81.
PMID: 26249237 DOI: 10.1007/s00192-015-2793-7

INTRODUCTION AND HYPOTHESIS: We aimed to compare palpatory and translabial ultrasound (TLUS) measurements of pelvic floor muscle (PFM) function with symptoms and signs of female pelvic organ prolapse (FPOP) to determine a possible association.
METHODS: We analysed data from 726 women with a mean age of 56 (SD 13.7, range 18-88) years, seen for symptoms of pelvic floor dysfunction between August 2011 and April 2013. The examination included a standardised interview and clinical assessment of FPOP with Pelvic Organ Prolapse Quantification (POP-Q) measurements, Modified Oxford Scale (MOS) grading and 4D TLUS.
RESULTS: Symptoms of prolapse were reported in 51.4% (373 out of 726) with a mean bother score of 5.8 (SD 2.91, range 0-10). A clinically significant POP (Incontinence Society [ICS]-POP-Q stage ≥ 2) in any compartment was diagnosed in 77.1%. Mean MOS was 2.4 (SD 1.1, range 0-5). Significant POP on TLUS was seen in 54.6% (389 out of 712). TLUS volumes at rest and on maximal PFM contraction were analysed on a desktop PC, to assess the degree of bladder neck (BN) cranioventral shift and levator antero-posterior (AP) diameter reduction, blinded against other data. Mean cranioventral BN shift was 7.11 (SD 4.36, range 0.32-25.32) mm and mean levator AP diameter reduction was 8.6 (SD 4.8, range 0.3-31.3) mm. MOS was strongly associated with subjective and objective POP (P ≤ 0.001), whereas this was not true for TLUS measurements of tissue displacement.
CONCLUSION: The MOS seems to be a more valid measure of PFM function than sonographically determined BN displacement or reduction of hiatal AP diameter observed on PFM contraction.

Matched MeSH terms: Muscle Contraction/physiology
Isolation and characterization of α-elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom

Rusmili MR, Tee TY, Mustafa MR, Othman I, Hodgson WC

Biochem Pharmacol, 2014 Mar 15;88(2):229-36.
PMID: 24440452 DOI: 10.1016/j.bcp.2014.01.004

Bungarus fasciatus is one of three species of krait found in Malaysia. Envenoming by B. fasciatus results in neurotoxicity due to the presence of presynaptic and postsynaptic neurotoxins. Antivenom, either monovalent or polyvalent, is the treatment of choice in systemically envenomed patients. In this study, we have isolated a postsynaptic neurotoxin which we named α-elapitoxin-Bf1b. This toxin has an approximate molecular weight of 6.9 kDa, with LCMS/MS data showing that it is highly homologous with Neurotoxin 3FTx-RI, a toxin identified in the Bungarus fasciatus venom gland transcriptome. α-Elapitoxin-Bf1b also shared similarity with short-chain neurotoxins from Laticauda colubrina and Pseudechis australis. α-Elapitoxin-Bf1b produced concentration- and time-dependent neurotoxicity in the indirectly-stimulated chick biventer cervicis muscle preparation, an effect partially reversible by repetitive washing of the preparation. The pA2 value for α-elapitoxin-Bf1b of 9.17 ± 0.64, determined by examining the effects of the toxin on cumulative carbacol concentration-response curves, indicated that the toxin is more potent than tubocurarine and α-bungarotoxin. Pre-incubation of Bungarus fasciatus monovalent and neuro polyvalent antivenom failed to prevent the neurotoxic effects of α-elapitoxin-Bf1b in the chick biventer cervicis muscle preparation. In conclusion, the isolation of a postsynaptic neurotoxin that cannot be neutralized by either monovalent and polyvalent antivenoms may indicate the presence of isoforms of postsynaptic neurotoxins in Malaysian B. fasciatus venom.

Matched MeSH terms: Muscle Contraction/physiology
Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus)

Nirthanan S, Charpantier E, Gopalakrishnakone P, Gwee MC, Khoo HE, Cheah LS, et al.

Br J Pharmacol, 2003 Jun;139(4):832-44.
PMID: 12813007

1 Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan krait Bungarus candidus, belongs to the poorly characterized subfamily of nonconventional three-finger toxins present in Elapid venoms. The current study details the pharmacological effects of candoxin at the neuromuscular junction. 2 Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve-muscle preparations and the tibialis anterior muscle of anaesthetized rats. In contrast to the virtually irreversible postsynaptic neuromuscular blockade produced by curaremimetic alpha-neurotoxins, the neuromuscular blockade produced by candoxin was rapidly and completely reversed by washing or by the addition of the anticholinesterase neostigmine. 3 Candoxin also produced significant train-of-four fade during the onset of and recovery from neuromuscular blockade, both, in vitro and in vivo. The fade phenomenon has been attributed to a blockade of putative presynaptic nicotinic acetylcholine receptors (nAChRs) that mediate a positive feedback mechanism and maintain adequate transmitter release during rapid repetitive stimulation. In this respect, candoxin closely resembles the neuromuscular blocking effects of d-tubocurarine, and differs markedly from curaremimetic alpha-neurotoxins that produce little or no fade. 4 Electrophysiological experiments confirmed that candoxin produced a readily reversible blockade (IC(50) approximately 10 nM) of oocyte-expressed muscle (alphabetagammadelta) nAChRs. Like alpha-conotoxin MI, well known for its preferential binding to the alpha/delta interface of the muscle (alphabetagammadelta) nAChR, candoxin also demonstrated a biphasic concentration-response inhibition curve with a high- (IC(50) approximately 2.2 nM) and a low- (IC(50) approximately 98 nM) affinity component, suggesting that it may exhibit differential affinities for the two binding sites on the muscle (alphabetagammadelta) receptor. In contrast, curaremimetic alpha-neurotoxins have been reported to antagonize both binding sites with equal affinity.

Matched MeSH terms: Muscle Contraction/physiology
Fulltext Glucose uptake during contraction in isolated skeletal muscles from neuronal nitric oxide synthase μ knockout mice

Hong YH, Frugier T, Zhang X, Murphy RM, Lynch GS, Betik AC, et al.

J Appl Physiol (1985), 2015 May 1;118(9):1113-21.
PMID: 25749441 DOI: 10.1152/japplphysiol.00056.2015

Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSμ(-/-) and nNOSμ(+/+) mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor N(G)-monomethyl-l-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSμ(-/-) and nNOSμ(+/+) mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (~4%) were detected in muscles from nNOSμ(-/-) mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSμ.

Matched MeSH terms: Muscle Contraction/physiology*
Fulltext No effect of NOS inhibition on skeletal muscle glucose uptake during in situ hindlimb contraction in healthy and diabetic Sprague-Dawley rats

Hong YH, Betik AC, Premilovac D, Dwyer RM, Keske MA, Rattigan S, et al.

Am J Physiol Regul Integr Comp Physiol, 2015 May 15;308(10):R862-71.
PMID: 25786487 DOI: 10.1152/ajpregu.00412.2014

Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/exercise, especially in individuals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0.1 ms, 35 V) with the contralateral hindlimb rested. After 10 min, the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME; 5 μM) or saline was continuously infused into the femoral artery of the contracting hindlimb until the end of contraction. Surprisingly, there was no increase in skeletal muscle NOS activity during contraction in either group. Local NOS inhibition had no effect on systemic blood pressure or muscle contraction force, but it did cause a significant attenuation of the increase in femoral artery blood flow in control and T2D rats. However, NOS inhibition did not attenuate the increase in muscle capillary recruitment during contraction in these rats. Muscle glucose uptake during contraction was significantly higher in T2D rats compared with controls but, unlike our previous findings in hooded Wistar rats, NOS inhibition had no effect on glucose uptake during contraction. In conclusion, NOS inhibition did not affect muscle glucose uptake during contraction in control or T2D Sprague-Dawley rats, and this may have been because there was no increase in NOS activity during contraction.

Matched MeSH terms: Muscle Contraction/physiology*