Muscle activity onset in the lumbar multifidus muscle recorded simultaneously by ultrasound imaging and intramuscular electromyography

BACKGROUND: Delayed anticipatory muscle activity response in deep abdominal and back muscles has been observed in patients with low back pain, indicative of a pathological condition. Muscle activity onset is traditionally recorded by intramuscular electromyography, but there is a need for a non-invasive and less cumbersome recording method in large clinical studies. An experimental study was carried out to explore whether high-frame rate m-mode ultrasound could measure anticipatory muscle responses ("onset") in the lumbar multifidus muscle reliably and comparably accurate to intramuscular electromyography. METHODS: Muscle activity onset was recorded by ultrasound m-mode and intramuscular electromyography. Ultrasound m-mode with a temporal resolution of 500 s(-1) (frames per second) was used to record rapid movements caused by muscle deformations in multifidus. In ultrasound m-mode, the frequency of each echo signal from 0.15 mm incremental depth levels is analysed. The frequency of these signals is proportional to the velocity of the interrogated tissue. The mean amplitude of the high-pass filtered echo signals within a pre-set depth range was plotted against time, and used to indicate onset. The results were compared to muscle activity onset in the multifidus recorded simultaneously by intramuscular electromyography. FINDINGS: High inter-rater agreement was found for visual determination of onset within both methods. The smallest detectable difference was 21 and 24 ms for electromyography and the ultrasound methods, respectively. The ultrasound m-mode method recorded muscle activity onset in the deep multifidus on average 16 ms (SD 21) later than intramuscular electromyography. For single trials, large variation and thus unacceptable method agreement was found. INTERPRETATION: Ultrasound m-mode imaging at high time resolution can detect onset of muscle activity comparably accurate to intramuscular electromyography, but with a small systematic delay that should be corrected for in onset determination by m-mode ultrasound. Regardless of recording method, onset estimates should be based on averaged values of repeated trials. Further studies are needed to explore the applicability of the ultrasound method in clinical settings.     

Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated

Hutchinson-Gilford progeria syndrome (HGPS), a rare disease that results in what appears to be premature aging, is caused by the production of a mutant form of prelamin A known as progerin. Progerin retains a farnesyl lipid anchor at its carboxyl terminus, a modification that is thought to be important in disease pathogenesis. Inhibition of protein farnesylation improves the hallmark nuclear shape abnormalities in HGPS cells and ameliorates disease phenotypes in mice harboring a knockin HGPS mutation (Lmna^HG/+). The amelioration of disease, however, is incomplete, leading us to hypothesize that nonfarnesylated progerin also might be capable of eliciting disease. To test this hypothesis, we created knockin mice expressing nonfarnesylated progerin (Lmna^nHG/+). Lmna^nHG/+ mice developed the same disease phenotypes observed in Lmna^HG/+ mice, although the phenotypes were milder, and mouse embryonic fibroblasts (MEFs) derived from these mice contained fewer misshapen nuclei. The steady-state levels of progerin in Lmna^nHG/+ MEFs and tissues were lower, suggesting a possible explanation for the milder phenotypes. These data support the concept that inhibition of protein farnesylation in progeria could be therapeutically useful but also suggest that this approach may be limited, as progerin elicits disease phenotypes whether or not it is farnesylated.     

Comparison of changes in abdominal muscle thickness between standing and crook lying during active abdominal hollowing using ultrasound imaging

To determine if transversus abdominis (TrA) demonstrates a greater increase in thickness on lower abdominal hollowing (LAH) in standing compared to crook lying.Muscle thickness measurements of TrA, addition of internal obliques (IO) and external obliques (EO) were measured using ultrasound imaging at rest and during LAH on 28 healthy controls (14 female, 14 male) in crook lying and standing.TrA demonstrated greater thickness changes on LAH in standing (+0.88 mm ± 0.12 mm). IO and EO demonstrated greater thickness changes on LAH in crook lying (+0.59 mm ± 0.08 mm and ?0.87 mm ± 0.12 mm, respectively). These differences were all significant (p < 0.001). Increased resting thickness was noted in standing in TrA (20.7%), IO (10.3%) and EO (1.2%). This increase was only significantly different between TrA and EO (P = 0.004).TrA showed significantly greater increases in thickness on LAH in standing compared to crook lying, and with greater specificity in relation to IO and maybe EO. If muscle thickness can be an indicator of muscle function or activity, then this suggests that TrA rehabilitation should be facilitated in positions of greater function, such as standing.     

Influence of feedback schedule in motor performance and learning of a lumbar multifidus muscle task using rehabilitative ultrasound imaging: a randomized clinical trial

BACKGROUND AND PURPOSE: Low back pain (LBP) may be associated with inadequate multifidus muscle function. Varying the frequency and timing of feedback may enhance acquisition and retention of multifidus muscle recruitment during exercise. SUBJECTS: Subjects without LBP (n=30) were randomly assigned to a constant (CON) or variable (VAR) feedback group. Twenty-eight subjects (mean age=28 years, SD=8.0; mean body mass index=24 kg/m(2), SD=0.70) completed training, and 23 completed retention testing. METHODS: Eight training sessions over 4 weeks included multifidus muscle exercise with rehabilitative ultrasound imaging (RUSI) feedback. Retention was assessed at 1 week and >or=1 month. RESULTS: At the start, both groups had similar performances of multifidus muscle recruitment (Fisher exact test, P=.26). Early in training, the CON group had good success (mean=80%) that was maintained at session 8 (mean=84%), with no difference between sessions 1 and 8 (Wilcoxon signed rank test, P=.19, 95% confidence interval [CI]=-9%, 42%). The VAR group gradually increased success (Wilcoxon signed rank test, P=.002, 95% CI=17%, 59%) between sessions 1 and 8. Both groups sustained their session 8 success when tested for short-term retention at 1 week (CON group: Wilcoxon signed rank test, P=.79; VAR group: Wilcoxon signed rank test, P=.36). At the long-term retention test, the VAR group outperformed the CON group (Wilcoxon score test, P=.04), indicating superior motor learning. DISCUSSION AND CONCLUSION: Variable feedback provided by RUSI resulted in greater success in lumbar multifidus muscle recruitment up to 3 to 4 months after training.     

Chronic alpha-tocopherol supplementation in rats does not ameliorate either chronic or acute alcohol-induced changes in muscle protein metabolism

Chronic alcohol muscle disease is characterized by reduced skeletal muscle mass precipitated by acute reduction in protein synthesis. The pathogenic mechanisms remain obscure, but several lines of evidence suggest that increased oxidative stress occurs in muscle in response to alcohol and this may be associated with impaired alpha-tocopherol status. Potentially, this implies a therapeutic role for alpha-tocopherol, especially as we have shown that supplemental alpha-tocopherol may increase the rate of protein synthesis in normal rats [Reilly, Patel, Peters and Preedy (2000) J. Nutr. 130, 3045-3049]. We investigated the therapeutic effect of alpha-tocopherol on plantaris muscle protein synthesis in rats treated either acutely, chronically or chronically+acutely with ethanol. Protein synthesis rates were measured with a flooding dose of L-[4-(3)H]phenylalanine. Protein, RNA and DNA contents were determined by standard laboratory methods. Ethanol caused defined metabolic changes in muscle, including decreased protein, RNA and DNA contents in chronically treated rats. In acute or chronic+acute studies, ethanol suppressed fractional rates of protein synthesis. alpha-Tocopherol supplementation did not ameliorate the effects of either acute, chronic or chronic+acute alcohol on plantaris muscle protein content or rates of protein synthesis. In control animals (not treated with alcohol), alpha-tocopherol supplementation decreased muscle protein content owing to increases in protein turnover (both synthesis and degradation). alpha-Tocopherol supplementation is not protective against the deleterious effects of alcohol on protein metabolism in skeletal muscle.     

Muscle swelling following blood flow‐restricted exercise does not differ between cuff widths in the proximal or distal portions of the upper leg

The purpose was to understand how wider cuffs, covering larger portions of the limb, may affect acute muscle swelling when used during low‐load knee extension exercise with blood flow restriction. A total of 96 individuals (53 females and 43 males) completed two visits, with visit one used for measuring maximal strength and arterial occlusion pressure (AOP), and visit two to compare between a narrow (5 cm) and a wide (12 cm) cuff for acute changes in muscle thickness and echo intensity following exercise. Ultrasound measurements were completed at a proximal and distal site within both legs, with the proximal site located beneath the cuff within the leg exercising using the wide cuff. Study findings indicate that the difference in acute changes for muscle thickness [median difference (95% credible interval) of 0.009 (?0.03, 0.05) cm] and echo intensity [median difference (95% credible interval) of 0.79 (?0.28, 1.89) AU] between cuff widths did not differ between proximal and distal sites. Additionally, acute changes in muscle thickness did not differ between cuff widths, sexes or participants who had AOP measured and those who were estimated. Lastly, acute changes in echo intensity did not differ between cuff widths and those who had AOP measured and those who were estimated. However, there was evidence showing how there might be greater reductions in echo intensity for females at the distal site. The previously observed attenuation of muscle growth under the cuff is unlikely to be related to differences in the acute muscle swelling response.     

Skeletal muscle oxygen saturation does not estimate mixed venous oxygen saturation in patients with severe left heart failure and additional severe sepsis or septic shock

Introduction  

Low cardiac output states such as left heart failure are characterized by preserved oxygen extraction ratio, which is in contrast to severe sepsis. Near infrared spectroscopy (NIRS) allows noninvasive estimation of skeletal muscle tissue oxygenation (StO₂). The aim of the study was to determine the relationship between StO₂ and mixed venous oxygen saturation (SvO₂) in patients with severe left heart failure with or without additional severe sepsis or septic shock.     

The antianginal agent, ranolazine, reduces myocardial infarct size but does not alter anatomic no-reflow or regional myocardial blood flow in ischemia/reperfusion in the rabbit

It has been suggested that ranolazine protects the ischemic/reperfused heart by reducing diastolic wall pressure during ischemia. However, there is limited information regarding the effect of ranolazine on the anatomic zone of no-flow in a model of acute myocardial occlusion/reperfusion. Before coronary artery occlusion (CAO), open-chest anesthetized rabbits were assigned to vehicle or ranolazine. Hearts received 60 minutes of CAO and 3 hours reperfusion. Ischemic risk zone was comparable in the 2 groups. Ranolazine significantly reduced infarct size. There was a non-significant trend for the no-reflow defect to be smaller in the ranolazine group. Regional myocardial blood flow was similar in both groups in the risk zone during ischemia and at 3 hours reperfusion. Heart rates were similar in both groups, whereas mean arterial pressure was reduced in the ranolazine group. While ranolazine was effective in reducing myocardial infarct size, the mechanism by which it did this was independent of improving perfusion during either ischemia or reperfusion, suggesting that ranolazine's effect of reducing infarct size involves alternative mechanisms.     

Amitriptyline or not, that is the question: pharmacogenetic testing of CYP2D6 and CYP2C19 identifies patients with low or high risk for side effects in amitriptyline therapy

BACKGROUND: Amitriptyline has been replaced in many countries by alternative and more expensive drugs based on claims of improved tolerability and toxicity and despite slightly reduced efficacy. Preliminary studies indicate that adverse effects could be linked to polymorphisms of drug-metabolizing enzymes, but information on their clinical impact remains scanty and includes mainly case reports. We conducted a prospective blinded two-center study seeking correlations between CYP2C19 and CYP2D6 genotypes, drug concentrations, adverse events, and therapy response. METHODS: Fifty Caucasian inpatients with at least medium-grade depressive disorder received amitriptyline at a fixed dose of 75 mg twice a day. Blood samples for concentration monitoring of amitriptyline and nortriptyline were taken weekly until discharge along with evaluations of depression (Hamilton Depression Scale and Clinical Global Impression Scale) and side effect (Dosage Record and Treatment Emergent Symptoms Scale; DOTES) scores. RESULTS: In a ROC analysis, nortriptyline but not amitriptyline concentrations correlated with side effects (DOTES sum score >or=5; area under the curve, 0.733; P = 0.008). Carriers of two functional CYP2D6 alleles had a significantly lower risk of side effects than carriers of only one functional allele (12.1% vs 76.5%; P = 0.00001). The lowest risk was observed for carriers of two functional CYP2D6 alleles combined with only one functional CYP2C19 allele [0 of 13 (0%) vs 9 of 11 (81.8%) for the high-risk group; P = 0.00004]. We found no correlations between drug concentrations or genotypes and therapeutic response. CONCLUSIONS: Combined pharmacogenetic testing for CYP2D6 and CYP2C19 identifies patients with low risk for side effects in amitriptyline therapy and could possibly be used to individualize antidepressive regimens and reduce treatment cost. Identification of genotypes associated with slightly reduced intermediate metabolism may be more important than currently anticipated. It could also be the key to demonstrating cost-effectiveness for CYP2D6 genotyping in critical dose drugs.