title: Skeletal muscle microbiopsy: a validation study of a minimally invasive technique Skeletal muscle effects of electrostimulation after COPD exacerbation: a pilot study African runners exhibit greater fatigue resistance, lower lactate accumulation, and higher oxidative enzyme activity. Comparison of lifestyle and structured interventions to increase physical activity and cardiorespiratory fitness: a randomized trial. Power output, isometric strength and steadiness in the leg muscles of pre- and postmenopausal women; the effects of hormone replacement therapy Atrophy responses to muscle inactivity. I. Cellular markers of protein deficits. Muscle atrophy and preferential loss of myosin in prolonged critically ill patients* Bad reporting does not mean bad methods for randomised trials: observational study of randomised controlled trials performed by the Radiation Therapy Oncology Group Discrepancy between published report and actual conduct of randomized clinical trials. Quantitative measurement of muscle fiber composition in a normal population. Muscle fiber characteristics in postmenopausal women with normal or impaired glucose tolerance.
abstract: The study of the peripheral skeletal muscle function in patients with chronic obstructive pulmonary disease ( COPD ) is of growing interest , but often requires biopsies , usually with the Bergström technique . The current study was design ed to test the validity of a minimally invasive technique : the microbiopsy . In 17 patients with COPD and four normal subjects , two specimens of the vastus lateralis were taken percutaneously under local anaesthesia , one with a 16-gauge needle ( microbiopsy ) and the other with the Bergström needle .  The enzymatic activity of citrate synthase ( CS ) and phosphofructokinase ( PFK ) , and the myosin heavy chain ( MyoHC ) composition were measured for both techniques . The subjects reported no pain or much less with the microbiopsy compared with the Bergström biopsy . The microbiopsy sample weight reached 55±17 mg . The two techniques showed excellent agreement for CS activity and MyoHC composition . The PFK activity did not differ statistically between the techniques , but the agreement was moderate . The agreement between both biopsy techniques was stable over time . The median ( range ) fibre number within the microbiopsy specimens was 144 ( 38–286 ) . In conclusion , the current study shows the feasibility and validity of a minimally invasive muscle biopsy technique that appears more comfortable for subjects , compared with the Bergström technique Muscle dysfunction is a major problem in chronic obstructive pulmonary disease ( COPD ) , particularly after exacerbations . We thus asked whether neuromuscular electrostimulation ( NMES ) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and /or alters muscle fibre distribution . A pilot r and omised controlled study of NMES lasting 6 weeks was carried out in 15 in- patients ( n=9 NMES ; n=6 sham ) following a COPD exacerbation . Stimulation was delivered to the quadriceps and hamstring muscles ( 35 Hz ) . Primary outcomes were quadriceps force and muscle oxidative stress . At the end of the study , quadriceps force improvement was statistically different between groups ( p=0.02 ) , with a significant increase only in the NMES group ( median ( interquartile range ) 10 ( 4.7–11.5 ) kg ; p=0.01 ) . Changes in the 6-min walking distance were statistically different between groups ( p=0.008 ) , with a significant increase in the NMES group ( 165 ( 125–203 ) m ; p=0.003 ) . NMES did not lead to higher muscle oxidative stress , as indicated by the decrease in total protein carbonylation ( p=0.02 ) and myosin heavy chain carbonylation ( p=0.01 ) levels . Finally , we observed a significant increase in type I fibre proportion in the NMES group . Our study shows that following COPD exacerbation , NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress Nine African and eight Caucasian 10-km runners resident at sea level volunteered . Maximal O2 consumption and peak treadmill velocity ( PTV ) were measured by using a progressive test , and fatigue resistance [ time to fatigue ( TTF ) ] was measured by using a newly developed high-intensity running test : 5 min at 72 , 80 , and 88 % of individual PTV followed by 92 % PTV to exhaustion . Skeletal muscle enzyme activities were determined in 12 runners and 12 sedentary control subjects . In a comparison of African and Caucasian runners , mean 10-km race time , maximal O2 consumption , and PTV were similar . In African runners , TTF was 21 % longer ( P < 0.01 ) , plasma lactate accumulation after 5 min at 88 % PTV was 38 % lower ( P < 0.05 ) , and citrate synthase activity was 50 % higher ( 27.9 + /- 7.5 vs. 18.6 + /- 2.1 micromol . g wet wt-1 . min-1 , P = 0.02 ) . Africans accumulated lactate at a slower rate with increasing exercise intensity ( P < 0.05 ) . Among the entire group of runners , a higher citrate synthase activity was associated with a longer TTF ( r = 0.70 , P < 0.05 ) , a lower plasma lactate accumulation ( r = -0.73 , P = 0.01 ) , and a lower respiratory exchange ratio ( r = -0.63 , P < 0.05 ) . We conclude that the African and Caucasian runners in the present study differed with respect to oxidative enzyme activity , rate of lactate accumulation , and their ability to sustain high-intensity endurance exercise CONTEXT Even though the strong association between physical inactivity and ill health is well documented , 60 % of the population is inadequately active or completely inactive . Traditional methods of prescribing exercise have not proven effective for increasing and maintaining a program of regular physical activity . OBJECTIVE To compare the 24-month intervention effects of a lifestyle physical activity program with traditional structured exercise on improving physical activity , cardiorespiratory fitness , and cardiovascular disease risk factors . DESIGN R and omized clinical trial conducted from August 1 , 1993 , through July 31 , 1997 . PARTICIPANTS Sedentary men ( n = 116 ) and women ( n = 119 ) with self-reported physical activity of less than 36 and 34 kcal/kg per day , respectively . INTERVENTIONS Six months of intensive and 18 months of maintenance intervention on either a lifestyle physical activity or a traditional structured exercise program . MAIN OUTCOME MEASURES Primary outcomes were physical activity assessed by the 7-Day Physical Activity Recall and peak oxygen consumption ( VO2peak ) by a maximal exercise treadmill test . Secondary outcomes were plasma lipid and lipoprotein cholesterol concentrations , blood pressure , and body composition . All measures were obtained at baseline and at 6 and 24 months . RESULTS Both the lifestyle and structured activity groups had significant and comparable improvements in physical activity and cardiorespiratory fitness from baseline to 24 months . Adjusted mean changes ( 95 % confidence intervals [ CIs ] ) were 0.84 ( 95 % CI , 0.42 - 1.25 kcal/kg per day ; P<.001 ) and 0.69 ( 95 % CI , 0.25 - 1.12 kcal/kg day ; P = .002 ) for activity , and 0.77 ( 95 % CI , 0.18 - 1.36 mL/kg per minute ; P = .01 ) and 1.34 ( 95 % CI , 0.72 - 1.96 mL/kg per minute ; P<.001 ) for VO2peak for the lifestyle and structured activity groups , respectively . There were significant and comparable reductions in systolic blood pressure ( -3.63 [ 95 % CI , -5.54 to -1.72 mm Hg ; P<.001 ] and -3.26 [ 95 % CI , -5.26 to -1.25 mm Hg ; P = .002 ] ) and diastolic blood pressure ( -5.38 [ 95 % CI , -6.90 to -3.86 mm Hg ; P<.001 ] and -5.14 [ 95 % CI , -6.73 to -3.54 mm Hg ; P<.001 ) for the lifestyle and structured activity groups , respectively . Neither group significantly changed their weight ( -0.05 [ 95 % CI , -1.05 to 0.96 kg ; P = .93 ] and 0.69 [ 95 % CI , -0.37 to 1.74 kg ; P = .20 ] ) , but each group significantly reduced their percentage of body fat ( -2.39 % [ 95 % CI , -2.92 % to -1.85 % ; P<.001 ] and -1.85 % [ 95 % CI , -2.41 % to -1.28 % ; P<.001 ] ) in the lifestyle and structured activity groups , respectively . CONCLUSIONS In previously sedentary healthy adults , a lifestyle physical activity intervention is as effective as a structured exercise program in improving physical activity , cardiorespiratory fitness , and blood pressure There are conflicting reports of the effects of hormone replacement therapy ( HRT ) on strength preservation in postmenopausal women , while any effect on power output has received little attention . Decreased steadiness of force generation has been reported in older muscles and may be related to the hormonal changes associated with the menopause , but the effect of HRT has not been investigated . We have studied the effect of HRT on strength , power output and isometric force steadiness in healthy women . Sixteen young ( aged 27.4±1.4 years , mean ± SEM ) and 29 postmenopausal women were studied . Fifteen of the latter were taking HRT ( 68.1±1.4 years , HRT+  ) and 14 ( 70.5±1.5 years , HRT− ) had never done so . During isometric quadriceps contractions the force steadiness ( coefficient of variation of force ) was measured at 10 , 25 , 50 and 100 % maximum voluntary contraction ( MVC ) . The average power generated by an explosive leg extension was recorded . The HRT− group generated less power ( 110.2±7.2 W ) than both the HRT+ ( 136.5±10.9 W , P=0.027 ) and young ( 136.2±5.8 W , P=0.027 ) subjects . Power output was similar in the HRT+ and younger subjects . The HRT− subjects were weaker than the younger ones ( 241.3±14.0 N vs. 297.6±13 N , P=0.006 ) . The strength of the HRT+ group ( 255.5±14 N ) was not significantly different to the other two groups . There was no difference in steadiness between the three groups at any of the force levels . HRT appears to maintain power output to a greater extent than isometric strength in postmenopausal women . There was no evidence for an effect of either age or HRT  on isometric steadiness in the quadriceps The goal of this study was to use the model of spinal cord isolation ( SI ) , which blocks nearly all neuromuscular activity while leaving the motoneuron muscle-fiber connections intact , to characterize the cellular processes linked to marked muscle atrophy . Rats r and omly assigned to normal control and SI groups were studied at 0 , 2 , 4 , 8 , and 15 days after SI surgery . The slow soleus muscle atrophied by approximately 50 % , with the greatest degree of loss occurring during the first 8 days . Throughout the SI duration , muscle protein concentration was maintained at the control level , whereas myofibrillar protein concentration steadily decreased between 4 and 15 days of SI , and this was associated with a 50 % decrease in myosin heavy chain ( MHC ) normalized to total protein . Actin relative to the total protein was maintained at the control level . Marked reductions occurred in total RNA and DNA content and in total MHC and actin mRNA expressed relative to 18S ribosomal RNA . These findings suggest that two key factors contributing to the muscle atrophy in the SI model are 1 ) . a reduction in ribosomal RNA that is consistent with a reduction in protein translational capacity , and 2 ) . insufficient mRNA substrate for translating key sarcomeric proteins comprising the myofibril fraction , such as MHC and actin . In addition , the marked selective depletion of MHC protein in the muscles of SI rats suggests that this protein is more vulnerable to inactivity than actin protein . This selective MHC loss could be a major contributor for the previously reported loss in the functional integrity of SI muscles . Collectively , these data are consistent with the involvement of pretranslational and translational processes in muscle atrophy due to SI Objective : Muscle weakness contributes to prolonged rehabilitation and adverse outcome of critically ill patients . Distinction between a neurogenic and /or myogenic underlying problem is difficult using routine diagnostic tools . Preferential loss of myosin has been suggested to point to a myogenic component . We evaluated markers of muscle atrophy and denervation , and the myosin/actin ratio in limb and abdominal wall skeletal muscle of prolonged critically ill patients and matched controls in relation to insulin therapy and known risk factors for intensive care unit-acquired weakness . Design : Secondary analysis of two large , prospect i ve , single-center r and omized clinical studies . Setting : University hospital surgical and medical intensive care unit . Patients : Critically ill patients and matched controls . Interventions : Intensive care unit patients had been r and omized to blood glucose control to 80–110 mg/dL with insulin infusion or conventional glucose management , where insulin was only administered when glucose levels rose above 215 mg/dL. Measurements and Main Results : As compared with controls , rectus abdominis and vastus lateralis muscle of critically ill patients showed smaller myofiber size , decreased mRNA levels for myofibrillar proteins , increased proteolytic enzyme activities , and a lower myosin/actin ratio , virtually irrespective of insulin therapy . Increased forkhead box O1 action may have played a role . Most alterations were more severe in patients treated with corticosteroids . Duration of corticosteroid treatment , independent of duration of intensive care unit stay or other risk factors , was a dominant risk factor for a low myosin/actin ratio . The immature acetylcholine receptor subunit & ggr ; messenger RNA expression was elevated in vastus lateralis , independent of the myosin/actin ratio . Conclusions : Both limb and abdominal wall skeletal muscles of prolonged critically ill patients showed downregulation of protein synthesis at the gene expression level as well as increased proteolysis . This affected myosin to a greater extent than actin , result ing in a decreased myosin/actin ratio . Muscle atrophy was not ameliorated by intensive insulin therapy , but possibly aggravated by corticosteroids Abstract Objective To determine whether poor reporting of methods in r and omised controlled trials reflects on poor methods . Design Observational study . Setting Reports of r and omised controlled trials conducted by the Radiation Therapy Oncology Group since its establishment in 1968 . Participants The Radiation Therapy Oncology Group . Outcome measures Content of reports compared with the design features described in the protocol s for all r and omised controlled trials . Results The method ological quality of 56 r and omised controlled trials was better than reported . Adequate allocation concealment was achieved in all trials but reported in only 42 % of papers . An intention to treat analysis was done in 83 % of trials but reported in only 69 % of papers . The sample size calculation was performed in 76 % of the studies , but reported in only 16 % of papers . End points were clearly defined and α and βerrors were prespecified in 76 % and 74 % of the trials , respectively , but only reported in 10 % of the papers . The one exception was the description of drop outs , where the frequency of reporting was similar to that contained in the original statistical files of the Radiation Therapy Oncology Group . Conclusions The reporting of method ological aspects of r and omised controlled trials does not necessarily reflect the conduct of the trial . Review ing research protocol s and contacting trialists for more information may improve quality assessment R and omized clinical trial ( RCT ) publications with inappropriate r and om-sequence generation , lack of allocation concealment , or imperfect blinding yield inflated estimates of effect compared to those in which adequate methods are described . RCTs that do not state methods used yield similar effect estimates , suggesting that inadequate methods were used . We compared RCT publications with investigator reports of actual practice for 40 rheumatology RCTs published in 1997/1998 . In RCTs in which these methods were not described in the trial reports and would thus have been characterized as " inadequate , " investigators reported using methods of r and om-sequence generation and allocation concealment that would be considered adequate in 77.4 and 78.1 % of RCTs , respectively . This suggests that , in contrast to previous reports , inadequate r and om-sequence generation and allocation concealment , per se , may not be a major problem in RCTs . Characterizing RCTs as " good " or " poor " quality based on the published report is likely to be inappropriate To obtain normative muscle morphology data on a healthy population recruited from a population survey , we examined  vastus lateralis biopsies from 58 men and 33 women , aged 26 - 67 years .  Biopsies were measured with automated , computer-aided techniques . Data were analyzed according to gender and age , and the influence of blood pressure , body mass index ( BMI ) , and smoking habits was also examined . Men had larger muscle fibers ( fiber area approximately 5400 microm(2 ) ) than women ( approximately 4000 microm(2 ) , P = 0.003 ) . No gender differences were seen in fiber composition , fiber roundness , percentage of connective tissue , or capillary density . Blood pressure did not influence fiber size or composition , but was correlated with fiber roundness in men . BMI was associated with fiber area in men , but not in women . Variations in age , smoking habits , and physical activity did not influence muscle morphology data substantially . Thus , in a normal population , men have larger muscle fibers than women , but similar fiber composition . Variation in gender , BMI , blood pressure , and physical activity may influence morphological features to a minor degree OBJECTIVE Muscle fiber characteristics are altered in type 2 diabetes . We studied whether these alterations also exist in impaired glucose tolerance ( IGT ) and whether they are determinants of insulin sensitivity and glucose tolerance in postmenopausal women . RESEARCH DESIGN AND METHODS Percutaneous muscle biopsies from the vastus lateralis muscle were obtained from 77 postmenopausal women aged 57 - 59 years : 50 women with normal glucose tolerance ( NGT ) and 27 with IGT .  The IGT group had a reduced insulin sensitivity compared with the NGT group ( euglycemic-hyperinsulinemic clamp ) ( P = 0.003 ) . RESULTS The groups did not differ in muscle fiber composition , as judged by the percentage of type I , IIa , or IIx fibers . In contrast , the IGT group had increased size of the IIa ( mean + /-SD 3,776+/-987 vs. 3,078+/-862 microm2 , P = 0.002 ) and IIx fibers ( 2,730+/-1,037 vs. 2,253+/-672 microm2 , P = 0.017 ) . There was a trend for the capillary diffusion areas ( the muscle area supplied by each capillary ) to be larger in the IGT group for the IIa ( 1,132+/-286 vs. 1,013+/-240 microm2 , P = 0.061 ) and IIx fibers ( 1,020+/-246 vs. 906+/-240 microm2 , P = 0.058 ) . In the entire group , insulin sensitivity correlated with the size of the type IIa fibers ( r = -0.28 , P = 0.013 ) , but not with the percentages of muscle fiber types . In a multiple regression , insulin sensitivity was determined by body fat content and HDL cholesterol level , while the size of the IIa fibers was not included in the model . Glucose tolerance was independently predicted by the number of capillaries/type I fiber , as well as by insulin sensitivity and triglyceride levels . CONCLUSIONS We conclude that although muscle fiber composition is not altered , women with IGT have larger type IIa and IIx muscle fibers and a trend for increased capillary diffusion areas for these fibers , compared with women with NGT . In the entire group , insulin sensitivity was determined mainly by body fat content , while muscle fiber capillarization may be of importance for glucose tolerance
target: Our meta analysis of a homogeneous set of studies is the first to provide valuable LLNs for fiber CSA according to fiber type and gender .
background: Skeletal muscle atrophy is a major systemic impairment in chronic diseases .
  Yet its determinants have been hard to identify because a clear research definition has not been agreed upon .
  The reduction in muscle fiber cross-sectional area ( CSA ) is a widely acknowledged marker of muscle atrophy , but no reference values for the muscle fiber CSA at the age of the onset of chronic disease have ever been published .