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Background: In cystic fibrosis (CF), pathophysiologic changes in the gastrointestinal tract lead to malnutrition and altered gut microbiome. Microbiome alterations have been linked to linear growth, gut inflammation and respiratory manifestations. Elucidating these gut microbiome alterations may provide insight into future nutritional management in CF., Methods: Infants were followed for 12-months at four sites in the United States (US-CF) and Australia (AUS-CF). 16S rRNA gene sequencing was performed on longitudinal stool samples. Associations between microbial abundance and age, antibiotic prophylaxis, malnutrition, and breast feeding were evaluated using generalized linear mixed models. Taxonomic and predictive functional features were compared between groups., Results: Infants with CF (N = 78) were enrolled as part of a larger study. AUS-CF infants had higher mean weight-for-age z-scores than US-CF infants (p = 0.02). A subset of participants (CF N = 40, non-CF disease controls N = 10) provided stool samples for microbiome analysis. AUS-CF infants had lower stool alpha diversity compared to US-CF infants (p < 0.001). AUS-CF infants had higher relative abundance of stool Proteobacteria compared to US-CF infants which was associated with antibiotic prophylaxis (p < 0.001). Malnutrition (weight-for-age <10th percentile) was associated with depleted Lactococcus (p < 0.001). Antibiotic prophylaxis (p = 0.002) and malnutrition (p = 0.012) were linked with predicted decreased activity of metabolic pathways responsible for short chain fatty acid processing., Conclusions: In infants with CF, gut microbiome composition and diversity differed between the two continents. Gut microbial diversity was not linked to growth. The relationship between malnutrition and antibiotic prophylaxis with reduced SCFA fermentation could have implications for gut health and function and warrants additional investigation., Competing Interests: Declaration of Competing Interest S. Davis served on the Vertex advisory board, (Copyright © 2023. Published by Elsevier B.V.)

Background: Cystic fibrosis (CF) pulmonary exacerbation (PEx) treatment guidelines suggest that Pseudomonas aeruginosa (Pa) airway infection be treated with two antipseudomonal agents., Methods: We retrospectively studied treatment responses for STOP2 PEx treatment trial (NCT02781610) participants with a history of Pa infection. Mean lung function and symptom changes from intravenous (IV) antimicrobial treatment start to Visit 2 (7 to 10 days later) were compared between those receiving one, two, and three+ antipseudomonal classes before Visit 2 by ANCOVA. Odds of PEx retreatment with IV antimicrobials within 30 days and future IV-treated PEx hazard were modeled by logistic and Cox proportional hazards regression, respectively. Sensitivity analyses limited to the most common one-, two-, and three-class regimens, to only IV/oral antipseudomonal treatments, and with more stringent Pa infection definitions were conducted., Results: Among 751 participants, 50 (6.7%) were treated with one antipseudomonal class before Visit 2, while 552 (73.5%) and 149 (19.8%) were treated with two and with three+ classes, respectively. Females and participants with a negative Pa culture in the prior month were more likely to be treated with a single class. The most common single, double, and triple class regimens were beta-lactam (BL; n = 42), BL/aminoglycoside (AG; n = 459), and BL/AG/fluoroquinolone (FQ; n = 73). No lung function or symptom response, odds of retreatment, or future PEx hazard differences were observed by number of antipseudomonal classes administered in primary or sensitivity analyses., Conclusions: We were unable to identify additional benefit when multiple antipseudomonal classes are used to treat PEx in people with CF and Pa., (Copyright © 2022. Published by Elsevier B.V.)

Background: In the STOP2 (Standardized Treatment of Pulmonary Exacerbations-2) study, intravenous (IV) antimicrobial treatment duration for adults with cystic fibrosis (CF) experiencing pulmonary exacerbations (PEx) was determined based on initial treatment response. The impact of home vs hospital care remains an important clinical question in CF. Our hypothesis was that STOP2 participants treated at home would have less improvement in lung function compared to those treated in the hospital., Methods: Treating clinicians determined PEx treatment location, which was a stratification factor for STOP2 randomization. Lung function, weight, and symptom recovery were evaluated by treatment location. Propensity scores and inverse probability treatment weighting were used to test for differences in clinical response by treatment location., Results: In all, 33% of STOP2 participants received IV antimicrobials in the hospital only, 46% both in the hospital and at home, and 21% at home only. Mean (95% CI) ppFEV 1 improvement was significantly (p < 0.05) lower for those treated at home only, 5.0 (3.5, 6.5), compared with at home and in the hospital, 7.0 (5.9, 8.1), and in the hospital only, 8.0 (6.7, 9.4). Mean weight (p < 0.001) and symptom (p < 0.05) changes were significantly smaller for those treated at home only compared to those treated in the hospital only., Conclusions: Compared to PEx treatment at home only, treatment in the hospital was associated with greater mean lung function, respiratory symptom, and weight improvements. The limitations of home IV therapy should be addressed in order to optimize outcomes for adults with CF treated at home., (Copyright © 2021. Published by Elsevier B.V.)

Background: C-reactive protein (CRP) has been proposed as a biomarker for pulmonary exacerbation (PEx) diagnosis and treatment response. CRP >75mg/L has been associated with increased risk of PEx treatment failure. We have analyzed CRP measures as biomarkers for clinical response during the STOP2 PEx study (NCT02781610)., Methods: CRP measures were collected at antimicrobial treatment start (V1), seven to 10 days later (V2), and two weeks after treatment end (V3). V1 log 10 CRP concentrations and log 10 CRP change from V1 to V3 correlations with clinical responses (changes in lung function and symptom score) were assessed by least squares regression. Odds of intravenous (IV) antimicrobial retreatment within 30 days and future PEx hazard associated with V1 and V3 CRP concentrations and V1 CRP >75 mg/L were studied by adjusted logistic regression and proportional hazards modeling, respectively., Results: In all, 951 of 982 STOP2 subjects (92.7%) had CRP measures at V1. V1 log 10 CRP varied significantly by V1 lung function subgroup, symptom score quartile, and sex, but not by age subgroup. V1 log 10 CRP correlated moderately with log 10 CRP change at V3 (r 2 =0.255) but less so with lung function (r 2 =0.016) or symptom (r 2 =0.031) changes at V3. Higher V1 CRP was associated with greater response. CRP changes from V1 to V3 only weakly correlated with lung function (r 2 =0.061) and symptom (r 2 =0.066) changes. However, V3 log 10 CRP was associated with increased odds of retreatment (P = .0081) and future PEx hazard (P = .0114)., Discussion: Despite consistent trends, log 10 CRP change was highly variable with only limited utility as a biomarker of PEx treatment response., Competing Interests: Declaration of Competing Interest The authors claim no financial conflicts of interest related to this work., (Copyright © 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Introduction: Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822., Methods: Median daily CRISS reduction (i.e., improvement) and covariates associated with CRISS reduction by Day 14 were assessed by logistic regression., Results: Among 173 subjects, median baseline CRISS was 49 [IQR 41, 56]; 93.6% had a CRISS reduction of ≥11 (minimal clinically important difference); median time to -11 reduction was 2 days [95% CI 2, 3]. The greatest median CRISS difference from baseline, on Day 17, was -26 [-29, -23]. Odds of -26 CRISS change by Day 14 were greater in subjects with higher baseline CRISS (P=.006) and younger ages (P=.041)., Conclusions: CRISS response has good dynamic range and may be a useful efficacy endpoint for PEx interventional trials. The optimal use of CRISS change as an endpoint remains uncharacterized., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: While the emergence of chronic and mucoid Pseudomonas aeruginosa (Pa) infection are both associated with poorer outcomes among CF patients, their relationship is poorly understood. We examined the longitudinal relationship of incident, chronic and mucoid Pa in a contemporary, young CF cohort in the current era of Pa eradication therapy., Methods: This retrospective cohort was comprised of patients in the U.S. CF Foundation Patient Registry born 2006-2015, diagnosed before age 2, and with at least 3 respiratory cultures annually. Incidence and age-specific prevalence of Pa infection stages (initial and chronic [≥ 3Pa+cultures in prior year]) and of mucoid Pa were summarized. Transition times and the interaction between Pa stage and acquisition of mucoid Pa were examined via Cox models., Results: Among the 5592 CF patients in the cohort followed to a mean age of 5.5years, 64% (n=3580) acquired Pa. Of those, 13% (n=455) developed chronic Pa and 17% (n=594) cultured mucoid Pa. Among those with mucoid Pa, 36% (211/594) had it on their first recorded Pa+culture, while mucoid Pa emerged at or after entering the chronic stage in 12% (73/594). Mucoidy was associated with significantly increased risk of transition to chronic Pa infection (HR=2.59, 95% CI 2.11, 3.19)., Conclusions: Two-thirds of early-diagnosed young children with CF acquired Pa during a median 5.6years of follow up, among whom 13% developed chronic Pa and 17% acquired mucoid Pa. Contrary to our hypothesis, 87% of young children who developed mucoid Pa did so before becoming chronically infected., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Pulmonary exacerbations (PEx) in cystic fibrosis (CF) are common and contribute to morbidity and mortality. Duration of IV antibiotic therapy to treat PEx varies widely in the US, and there are few data to guide treatment decisions., Methods: We combined a survey of CF stakeholders with retrospective analyses of a recent observational study of CF PEx to design a multicenter, randomized, prospective study comparing the efficacy and safety of different durations of IV antibiotics for PEx to meet the needs of people with CF and their caregivers., Results: IV antibiotic duration was cited as the most important PEx research question by responding CF physicians and top concern among surveyed CF patients/caregivers. During PEx, forced expiratory volume in 1s (FEV 1 % predicted) and symptom responses at 7-10days of IV antibiotics identified two distinct groups: early robust responders (ERR) who subsequently experienced greater FEV 1 improvements compared to non-ERR (NERR). In addition to greater FEV 1 and symptom responses, only 14% of ERR patients were treated with IV antibiotics for >15days, compared with 45% of NERR patients., Conclusions: A divergent trial design that evaluates subjects' interim improvement in FEV 1 and symptoms to tailor randomization to IV treatment duration (10 vs. 14days for ERR, 14 vs. 21days for NERR) may alleviate physician and patient concerns about excess or inadequate treatment. Such a study has the potential to provide evidence necessary to standardize IV antibiotic duration in CF PEx care -a first step to conducting PEx research of other treatment features., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Given the variability in pulmonary exacerbation (PEx) management within and between Cystic Fibrosis (CF) Care Centers, it is possible that some approaches may be superior to others. A challenge with comparing different PEx management approaches is lack of a community consensus with respect to treatment-response metrics. In this analysis, we assess the feasibility of using different response metrics in prospective randomized studies comparing PEx treatment protocols., Methods: Response parameters were compiled from the recent STOP (Standardized Treatment of PEx) feasibility study. Pulmonary function responses (recovery of best prior 6-month and 12-month FEV 1 % predicted and absolute and relative FEV 1 % predicted improvement from treatment initiation) and sign and symptom recovery from treatment initiation (measured by the Chronic Respiratory Infection Symptom Score [CRISS]) were studied as categorical and continuous variables. The proportion of patients retreated within 30days after the end of initial treatment was studied as a categorical variable. Sample sizes required to adequately power prospective 1:1 randomized superiority and non-inferiority studies employing candidate endpoints were explored., Results: The most sensitive endpoint was mean change in CRISS from treatment initiation, followed by mean absolute FEV 1 % predicted change from initiation, with the two responses only modestly correlated (R 2 =.157; P<0.0001). Recovery of previous best FEV 1 was a problematic endpoint due to missing data and a substantial proportion of patients beginning PEx treatment with FEV 1 exceeding their previous best measures (12.1% >12-month best, 19.6% >6-month best). Although mean outcome measures deteriorated approximately 2-weeks post-treatment follow-up, the effect was non-uniform: 62.7% of patients experienced an FEV 1 worsening versus 49.0% who experienced a CRISS worsening., Conclusions: Results from randomized prospective superiority and non-inferiority studies employing mean CRISS and FEV 1 change from treatment initiation should prove compelling to the community. They will need to be large, but appear feasible., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Objective: We reviewed our experience to determine if the decremental pattern during low frequency repetitive nerve stimulation (LF-RNS) distinguishes between the Lambert-Eaton myasthenic syndrome (LEMS) and myasthenia gravis (MG)., Methods: LF-RNS studies were reviewed from 34 LEMS and 44 MG patients, 4 of whom had antibodies to muscle specific kinase (MuSK). In each train we calculated the ratio between the early and the later decrement. Receiver-operator characteristic curves were calculated to determine the ratio that best distinguished between LEMS and MG., Results: The late decrement was more often greater in LEMS and the converse was true in MG, but with some overlap in values in individual patients. A late decrement more than 102% of the early decrement discriminated between LEMS and MG in 90% of studies. The decremental pattern in MG patients with MuSK antibodies resembled that in LEMS., Conclusion: When the decrement becomes progressively greater during low frequency RNS, the patient is more likely to have LEMS than MG, and in MG, is more likely to have MuSK antibodies., Significance: A progressive decrement in patients otherwise felt to have MG should prompt further clinical, serological and electrodiagnostic tests. Further studies are needed to assess the decremental pattern in MuSK MG., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To examine the clinical manifestations and patterns of electromyographic abnormalities in MuSK-Ab positive myasthenia gravis., Methods: The clinical evaluations and electrodiagnostic testing results of 20 MuSK-Ab positive myasthenia gravis patients were retrospectively reviewed and compared with matched AChR-Ab positive (N = 72) and MuSK-Ab negative/AChR-Ab negative (N = 24) patients., Results: MuSK-Ab positive patients were younger and more frequently female and African-American, and compared to the AChR-Ab positive patients, were more likely to present with respiratory symptoms or neck extension weakness. MuSK-Ab positive patients were less likely to have abnormal jitter in a limb muscle: only 59% had abnormal jitter in the extensor digitorum communis muscle, compared to 80% of the AChR-Ab negative/MuSK-negative patients and 91% of the AChR-Ab positive patients., Conclusions: Our MuSK-Ab positive patients not only differ demographically from our MuSK-Ab negative cohort, but they also appear to have a more limited distribution of SFEMG abnormalities., Significance: The possibility that electrophysiologic abnormalities may not be widely distributed should be considered during electrodiagnostic evaluation of suspected MuSK-Ab positive MG and in selecting muscles for molecular, morphologic, or microphysiologic studies in this condition.

Objective: The purpose of this study was to compare results of electromyographic assessment of muscular recruitment between nulliparous control subjects without pelvic floor dysfunction and parous subjects with genuine stress urinary incontinence and with pelvic organ prolapse. Interference pattern analysis is an electromyographic technique that reproducibly measures muscular recruitment by detecting both "turns" in the electromyographic signal produced by positive and negative peaks of the motor unit potentials and motor unit potential amplitude. Fewer turns can indicate loss of motor units or failure of central activation of contraction, whereas greater amplitude can indicate reinnervation after nerve damage., Study Design: We performed concentric needle electrode electromyographic examinations of the levator ani and external anal sphincter in 15 nulliparous control subjects and 20 parous subjects with abnormalities (n = 9 with genuine stress urinary incontinence, n = 11 with stage III or IV pelvic organ prolapse). We made digital recordings at multiple sites at rest and with moderate and maximal contraction. Interference pattern analysis yielded the number of turns per second and the mean signal amplitude (in microvolts) for each site at each contraction level. We compared individual patient data with data from the healthy population by means of cloud analysis. Mean values of number of turns per second and mean amplitude in each group were then compared with nonparametric methods and regression models., Results: Mean ages were 28.7 years (range, 20-49 years) for the control group, 54.3 years (range, 35-75 years) for subjects with genuine stress urinary incontinence, and 65 years (range, 41-77 years) for subjects with pelvic organ prolapse. Median clinical levator ani strengths were 9 (range, 5-9) in the control group, 5 (range, 2-7) in the genuine stress urinary incontinence group, and 5 (range, 2-8) in the pelvic organ prolapse group. Median external anal sphincter strengths were 9 (range, 7-9) in the control group, 5 (range, 3-9) in the genuine stress urinary incontinence group, and 8 (range, 4-9) in the pelvic organ prolapse group. The external anal sphincters of subjects with pelvic organ prolapse had the highest percentage of abnormal study results according to cloud analysis. Mean number of turns per second in levators was greater in control subjects than in subjects with abnormalities (P =.034). We found similar differences in number of turns per second for the external anal sphincter (P =.004). In contrast, we did not find differences between groups in mean amplitude in either the levator ani or the external anal sphincter. Comparison of patients with genuine stress urinary incontinence versus subjects with pelvic organ prolapse showed no significant difference in the number of turns per second in either muscle. Mean amplitude was greater in the pelvic organ prolapse group than in the genuine stress urinary incontinence group for both muscles (levator ani, P =.028; external anal sphincter, P =.048). Neither mean amplitude nor the number of turns per second could be predicted by clinically estimated levator ani strength, age, or fecal incontinence., Conclusion: Compared with nulliparous control subjects, patients with genuine stress urinary incontinence and pelvic organ prolapse had changes in the levator ani and external anal sphincter consistent with either motor unit loss or failure of central activation, or both. Subjects with pelvic organ prolapse had findings consistent with greater recovery than was found in those with genuine stress urinary incontinence. Measures of recruitment by interference pattern analysis correlated better with clinical external anal sphincter strength than with levator ani strength and were independent of age.

Objectives: Our aims were to introduce a method of digital quantitative electromyography of the levator ani and external anal sphincter muscles and to establish reference values., Study Design: Fifteen nulliparous, symptom-free women underwent concentric needle electromyographic examination of the levator ani and external anal sphincter. We sampled the levator ani transvaginally at 4 sites and the external anal sphincter at 2 sites. The signal was filtered and amplified, and digital recordings were made at 3 levels of voluntary activation at each site. Analyses of motor unit action potentials and interference patterns were performed with the use of these taped signals. Normal ranges were generated and compared with those established for other striated muscles., Results: The mean age of the subjects was 28.7+/-7.5 years. A median of 24 motor unit action potentials was recorded in each levator ani, and a median of 6 was recorded in each external anal sphincter. Parameters of the levator ani action potentials were significantly greater than those of the external anal sphincter in amplitude (0.48 vs. 0.37 mV; P =.001), duration (10.40 vs. 8.27 ms; P =.002), number of turns per second (2. 80 vs. 2.28; P<.001), and area (0.65 vs. 0.36; P<.001). Parameters of the interference patterns were significantly greater in the levator ani than in the external anal sphincter in number of turns per second (241.6 vs. 183.9; P =.015), amplitude (302.7 vs. 225.3 microV; P<.0001), activity (95.6 vs 61.2; P =.004), envelope size (861.1 vs 567.6 microV; P<.0001), and number of small segments (105. 8 vs 81.4; P =.047). There were no significant differences between levator ani, external anal sphincter, and published parameters from the biceps muscle with regard to amplitude and duration of motor unit action potentials., Conclusions: Electromyography of the levator ani and external anal sphincter is feasible and well tolerated. Our findings confirm that the levator ani muscle has larger, more readily recruited motor units than does the external anal sphincter. Ranges for important quantitative electromyographic parameters for these muscles are similar to those published for the biceps.

Computer simulations indicate that measurements of the area of motor unit action potentials (MUAPs) recorded with a concentric needle electrode could be useful in differentiating between neuropathy and myopathy. However, MUAP area varies markedly when the position of the recording electrode is changed only slightly within the motor unit territory, mainly because of the changes in the MUAP amplitude produced by only slight electrode movements. The ratio of MUAP area to amplitude is much less affected by changes in electrode position and measures the 'thickness' of the MUAP wave form. We found that the MUAP area:amplitude ratio was reduced in myopathy even when the MUAP amplitude was normal or increased. In patients with neuropathy, the MUAP amplitude and area both tend to be increased while their ratio is normal or increased. The diagnostic yield obtained from MUAP area, amplitude and their ratio in combination was similar to that obtained using measurements of MUAP duration. Unlike the MUAP duration, the MUAP area, amplitude and area:amplitude ratio are robust features of the MUAP in that they are less sensitive to the signal-to-noise ratio and inter-operator differences in signal selection.

Electrophysiological investigations of the effects of bath-applied prednisolone at the neuromuscular junction were performed in muscles from normal rats and rats with experimental autoimmune myasthenia gravis (EAMG). In muscles from both groups, prednisolone reversible and significantly depressed the amplitudes of minature end-plate potentials (MEPPs), end-plate potentials (EPPs) and indirectly elicited action potentials (APs) without affecting resting membrane potentials. Prednisolone also caused a significant reduction in EPP rise time to peak and half-decay time while markedly increasing MEPP frequency and AP rise time to peak and duration. These effects were shown to be dose-dependent. The percentage decrease in amplitude after prednisolone perfusion was similar for EPPs and MEPPs, indicating that the depressive effect of prednisolone at the junction is postsynaptic. In all of the parameters studied, the percentage effect of prednisolone was the same in EAMG and normal preparations. No stimulus-linked repetitive EPPs or APs were observed after prednisolone. It is concluded that prednisolone has a depressive effect on neuromuscular transmission, but that this occurs only at high concentrations of the drug which are not achieved during the treatment of myasthenia gravis.

Using computer simulation techniques, reinnervation of motor units (MUs) was studied by increasing the number of muscle fibers in the MU without changing the MU territory. The fiber density (FD) measured by single fiber EMG electrodes, the amplitude, area and number of turns of concentric needle (CN) EMG motor unit action potentials (MUAPs) and the amplitude of macro EMG MUAPs were most affected by partial reinnervation changes. The values of these features increased during simulated advanced reinnervation, as did the number of CNEMG MUAPs that had increased numbers of phases or turns and the mean CNEMG MUAP duration. The increase in macro EMG MUAP amplitude, FD and CNEMG MUAP area were proportional to the increase in the number of muscle fibers in the MU. When loss of muscle fibers due to so-called MU fractionation was simulated, values of all EMG features fell, but were still increased compared to normal. Two patterns of change in SFEMG and macro EMG values were identified that may distinguish between recordings made from reinnervated low force threshold MUs and those from higher force threshold MUs.

Serum was obtained from 7 patients with the Lambert-Eaton myasthenic syndrome (LES), 3 patients with small-cell carcinoma of the lung (SCCL), and 9 healthy control subjects. Serum samples were applied in vitro to the rat neuromuscular junction (for 1-3 h for control LES sera; 4 h for SCCL sera), following which the pre- and postjunctional physiological effects of serum factors were studied in the presence of 10 mM [Mg2+]o. All sera produced a marked reduction in the frequency of spontaneous miniature end-plate potentials (MEPPs), while causing slight to moderate changes in MEPP amplitude. There were no consistent changes in the quantum content of the impulse-evoked end-plate potentials, though the serum from one LES patient significantly and reversibly inhibited the evoked quantal release. No significant effect was found when a human intercostal muscle was exposed to serum from another LES patient for 2 h. Therefore, when applied in vitro on a short-term basis, the putative LES autoantibodies do not consistently react with voltage-dependent calcium channels in the motor nerve terminal and thus fail to reproduce the physiologic abnormality of the syndrome. We suggest that the pathogenic IgG molecules may require more than 3h of incubation in order to gain access to, and inhibit the function of, the prejunctional Ca2+ channels.

This study was performed to compare different techniques of analyzing the electromyographic interference pattern (IP). Recordings were made from the biceps muscle with a concentric needle electrode at different sites and at different constant levels of voluntary contraction. The number of turns per second (NT), the mean amplitude change between successive turns (MA) and NT:MA ratio were determined for epochs of 1 sec duration. Normal limits of individual epoch NT:MA ratios and the mean value of NT:MA ratio obtained from all epochs in each muscle were determined. The mean NT:MA ratio was less in normal males than in females. IP recordings were made in the biceps muscle of 69 patients with neuropathy and 54 patients with myopathy, though this muscle was not necessarily affected by the disease in all patients. The IP was abnormal by visual inspection in 82% of patients compared to 61% based on NT:MA ratio and 74% using a technique that automatically quantitates some features of the IP that are assessed subjectively by an electromyographer. All techniques demonstrated IP abnormalities in more than 80% of the muscles that were moderately to severely weak. Though measuring the NT:MA ratio without monitoring the force of contraction is not as sensitive as other IP analysis techniques, it may be useful in quantitating abnormalities when other techniques are not available.

Patients with myasthenia gravis (MG) have increased tolerance to the neuromuscular blocking properties of suxamethonium (SCh) and decamethonium (C10) and exhibit a reversal of the C10-induced block by neostigmine. The effects of these drugs were compared in forelimb flexor digitorum longus muscle from normal rats and from rats with experimental autoimmune myasthenia gravis (EAMG) to investigate the similarity of EAMG to MG. The depolarization induced by 1, 5, 10 and 25 microM SCh or C10 at the motor end-plates was significantly higher in normal than in EAMG muscle. However, both normal and EAMG end-plates responded in a similar qualitative manner to each drug. The depolarization produced by SCh was typically maintained until the drug was washed from the bath. The depolarization produced by C10 tended to decrease after reaching its peak despite continued application of the drug. With both drugs, miniature end-plate potential (MEPP) amplitude reduction is maintained until a saline wash. Neostigmine interaction with SCh and C10 in normal and EAMG muscle was compared by measuring isometric twitch tension in vitro. Neostigmine potentiated the neuromuscular block produced by either SCh or C10 in both normal and EAMG muscle. Thus muscle from rats with EAMG shares with MG an increased tolerance to SCh and C10 when compared to normal muscle but does not exhibit the qualitatively different interaction of C10 affected muscle with neostigmine that is found in MG patients. This and other studies comparing EAMG and MG indicate that EAMG is an appropriate model of MG but differences such as we have noted should be considered when extrapolating data from EAMG to the human disease.