Biomedical subjects

Graham J Kemp

Publications and source records attributed to Graham J Kemp.

13 recordsLinked to original sources

PubMed2006

Exercise capacity and quadriceps muscle metabolism following training in subjects with COPD.

The aim of the study was to determine whether 16 sessions of exercise training, completed twice weekly, alters exercise capacity, quadriceps muscle metabolism, cross-sectional area (CSA) and strength in subjects with chronic obstructive pulmonary disease (COPD). We studied (a) 10 COPD subjects (mean age+/-sem = 71+/-2 years; FEV1 = 0.99+/-0.1 L) before and after 16 sessions of exercise training, and (b) 10 healthy subjects (age = 68+/-3 years). The COPD subjects underwent an incremental peak exercise test using a cycle ergometer and a 6-min walk test: both improved following exercise training (P < 0.05). Magnetic resonance spectroscopy measurements, in quadriceps muscle, of post-exercise phosphocreatinine (PCr) recovery kinetics were used to assess mitochondrial function in vivo: in the COPD subjects pre-training this was 19+/-8% lower than in healthy subjects (P = 0.03), but a 38+/-12% increase was seen in the COPD subjects following training (P = 0.003). Magnetic resonance imaging was used to assess quadriceps CSA: after training in the COPD subjects this showed a 7+/-2% increase (P = 0.03). Quadriceps strength, measured by the best of five maximum voluntary contractions, also showed a 32+/-11% increase in the COPD subjects (P = 0.007). Sixteen sessions of exercise training, performed twice weekly, increased exercise capacity as well as quadriceps mitochondrial capacity, CSA and strength in the subjects with COPD.

Aged↗

PubMed2006

Aerobic exercise and muscle metabolism in patients with mitochondrial myopathy.

Exercise therapy improves mitochondrial function in patients with mitochondrial myopathy (MM). We undertook this study to determine the metabolic abnormalities that are improved by exercise therapy. This study identified metabolic pathology using (31)P-magnetic resonance spectroscopy and magnetic resonance imaging (MRI) in a group of patients with MM compared to a control group matched for age, gender, and physical activity. We also observed the effect of exercise therapy for 12 weeks on muscle metabolism and physical function in the MM group. During muscle activity, there was impaired responsiveness of the mitochondria to changes in cytosolic adenosine diphosphate concentration, increased dependence on anaerobic energy pathways, and an adaptive increase in proton efflux in patients with MM. Following exercise therapy, mitochondrial function and muscle mass improved without any change in proton efflux rate. These metabolic findings were accompanied by improvements in functional ability. We conclude that there are significant metabolic differences between patients with MM and a control population, independent of age, gender, and physical activity. Exercise therapy can assist in improving mitochondrial function in MM patients.

Adult↗

PubMed2005

Matrix metalloproteinase expression is related to angiogenesis and histologic grade in spindle cell soft tissue neoplasms of the extremities.

We defined the immunocytochemical expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in benign soft tissue neoplasms, fibromatoses, and sarcomas, together with the activity of gelatinase MMPs and TIMPs measured by zymography and reverse zymography in a subset of cases. The most strongly expressed MMP in all tumors was MMP-1, with weaker expression of MMP-10, MMP-11, and MMP-14 in most tumors. Nuclear expression of MMP-1, MMP-8, and MMP-13 was an unusual feature. TIMP-2 was expressed in all tumors, with stronger expression in fibromatoses than in sarcomas. Fibromatoses and high-grade sarcomas showed greater MMP-1 expression than other groups, and endothelial MMP-2 expression was more extensive in sarcomas. Differences in MMP and TIMP expression might be linked to the biologic behavior of soft tissue neoplasms. The activation of endothelial MMP-2 linked to widespread MMP-14 expression provides a mechanism for sarcomas to modulate their matrix and facilitate angiogenesis.

Adolescent↗

PubMed2004

Abnormal mitochondrial function and muscle wasting, but normal contractile efficiency, in haemodialysed patients studied non-invasively in vivo.

BACKGROUND: Muscle dysfunction, which contributes to morbidity in patients on haemodialysis, has several manifestations and a number of possible causes. We applied the non-invasive techniques of (31)P-magnetic resonance spectroscopy ((31)P-MRS), magnetic resonance imaging (MRI) and near-infrared spectroscopy (NIRS) to calf muscle of dialysed patients to define the abnormalities in muscle cross-sectional area (CSA), contractile efficiency, mitochondrial function and vascular O(2) supply. METHODS: We performed (31)P-MRS/NIRS/MRI studies on the lateral gastrocnemius during isometric plantarflexion and recovery in 23 male patients on haemodialysis (age 24-71 years; haemoglobin 9.9-14.2 g/dl; bicarbonate 17-30 mmol/l; urea reduction ratio 53-77%; parathyroid hormone 1-95 U/l) and 15 male controls (age 29-71 years). To understand the relationships between calf CSA and body mass we also performed MRI only in a further six male patients and 18 male controls. RESULTS: In patients, exercise duration was 30+/-11% lower than in controls. Muscle CSA was lower by 26+/-5%, but contractile efficiency (force/CSA/ATP turnover) was normal. Slowing of post-exercise phosphocreatine (PCr) recovery implied a 22+/-5% defect in effective 'mitochondrial capacity'. That PCr recovery was slow relative to NIRS recovery suggests that this is largely an intrinsic mitochondrial problem (not the result of impaired O(2) supply), one which, furthermore, correlated with CSA. Urea reduction ratio showed a negative correlation with body mass and CSA, but none with PCr rate constant. CONCLUSIONS: The relationships to urea reduction ratio reflect the effect of muscle mass on dialysis efficiency, rather than direct effects on muscle CSA or metabolism. The relationship between PCr recovery and calf CSA suggests a role for the mitochondrial defect, whatever its cause, in the development of muscle wasting, although a common cause (e.g. physical inactivity) for both abnormalities cannot be ruled out.

Humans↗

PubMed2004

Mitochondrial dysfunction in chronic ischemia and peripheral vascular disease.

In peripheral vascular disease, impaired muscle energy metabolism is assumed to be due mainly to defective vascular O2 supply, the resulting cellular hypoxia inhibiting oxidative ATP synthesis. Older work suggested a compensatory increase in muscle aerobic enzymes, but more recent studies suggest a relative decrease in some mitochondrial components and an accumulation of damage in mitochondrial DNA, perhaps due to reactive oxygen species. However, to establish whether in vivo muscle mitochondria suffer from anything other than a low concentration of O2 will require more knowledge of the mitochondrial behaviour at low PO2, and the actual cell PO2 during exercise.

Journal Article↗

PubMed2004

Measuring myoelectric fatigue of the serratus anterior in healthy subjects and patients with long thoracic nerve palsy.

Proper function of serratus anterior plays a vital role in the movement and stability of the scapula, and thus of the glenohumeral joint and the upper limb. The unique anatomy of this muscle makes direct measurements of its fatigue properties impossible. Here we describe for the first time indirect measurements of the myoelectric manifestations of fatigue in the serratus anterior. Eight healthy volunteers (29-35 years) were tested, four of them on two different occasions, using two exercise protocols (60 s isometric maximum upward force in 120 degrees arm flexion, and 60 s maximum forward force at 90 degrees arm flexion) with simultaneous recording by surface and wire electrodes applied according to established methods. Signals were analysed to obtain the rate of fall of median EMG frequency and the rate of rise of amplitude. Both exercise protocols gave similar results. Frequency-slope measurements (mean rate of fall 0.6+/-0.1% initial value per second (% s(-1)) with both surface and wire electrodes) were more precise than those of amplitude (mean rate of rise 2.6+/-0.3% s(-1) with surface electrodes, only 1.3+/-0.2% s(-1) with wire electrodes). Surface electrodes gave much lower variation than fine wires, the coefficient of variation of slopes for surface electrodes being approximately 20-40% both between studies in a single subject and between subjects. In 5 patients (aged 22-59 years) recovering from long thoracic nerve palsy studied using surface electrodes the frequency slopes was normal (0.6+/-0.1% s(-1)), while the amplitude slope was reduced (0.9+/-0.4% s(-1), P = 0.01). This shows abnormal fatigue properties of the reinnervated muscle and a dissociation between the frequency and amplitude manifestations of fatigue.

Adult↗

PubMed2004

The role of cutaneous sensation in the motor function of the hand.

We studied the effect of abolishing cutaneous sensation (by infiltrating local anaesthetic around the median nerve at the wrist) on the ability of 10 healthy volunteers (a) to maintain a submaximal isometric pinch-grip force for 30 s without visual feedback, and (b) to perform a fine finger-manipulation 'handwriting' task. Blocking cutaneous sensation had no effect on ability to maintain pinch force, suggesting that muscle afferents have the major role in force-control feedback. However, a near-linear fall in force, present with or without block (mean slope=-1.3+/-0.2% s(-1)), which cannot be attributed to motor fatigue, reveals a shortcoming of the afferent feedback system. Blocking cutaneous sensation did impair ability to perform the more demanding writing task, as judged by an 18+/-6% increase in the length of the path between target points, a 22+/-9% increase in the duration of the movement and a 63+/-24% in 'normalised averaged rectified jerk', an averaged time-derivative of acceleration (all significantly nonzero, P < 0.04). These experiments demonstrate the relative importance of muscular and cutaneous afferent feedback on two aspects of hand performance, and provide a way to quantify the deficit resulting from the lack of cutaneous sensation.

Electromyography↗

PubMed2003

ATP synthesis and proton handling in muscle during short periods of exercise and subsequent recovery.

We used (31)P-magnetic resonance spectroscopy to study proton buffering in finger flexor muscles of eight healthy men (25-45 yr), during brief (18-s) voluntary finger flexion exercise (0.67-Hz contraction at 10% maximum voluntary contraction; 50/50 duty cycle) and 180-s recovery. Phosphocreatine (PCr) concentration fell 19 +/- 2% during exercise and then recovered with half time = 0.24 +/- 0.01 min. Cell pH rose by 0.058 +/- 0.003 units during exercise as a result of H(+) consumption by PCr splitting, which (assuming no lactate production or H(+) efflux) implies a plausible non-P(i) buffer capacity of 20 +/- 3 mmol. l intracellular water(-1). pH unit(-1). There was thus no evidence of significant glycogenolysis to lactate during exercise. Analysis of PCr kinetics as a classic linear response suggests that oxidative ATP synthesis reached 48 +/- 2% of ATP demand by the end of exercise; the rest was met by PCr splitting. Postexercise pH recovery was faster than predicted, suggesting "excess proton" production, with a peak value of 0.6 +/- 0.2 mmol/l intracellular water at 0.45 min of recovery, which might be due to, e.g., proton influx driven by cellular alkalinization, or a small glycolytic contribution to PCr resynthesis in recovery.

Adenosine Triphosphate↗

PubMed2003

Arthroscopic capsular shrinkage of the shoulder for the treatment of patients with multidirectional instability: Minimum 2-year follow-up.

PURPOSE: The study goal was to evaluate the arthroscopic treatment of patients with multidirectional instability of the shoulder (MDI). MDI is a disabling condition as a result of pain and restriction of activity. The treatment of MDI is primarily nonsurgical (supervised physiotherapy). TYPE OF STUDY: Prospective cohort study. METHODS: Arthroscopic capsular shrinkage, using a bipolar radiofrequency system, was performed in 32 patients (33 shoulders). The mean age was 27 years (range, 15 to 49). The Constant score was used for assessment preoperatively and at 6-month intervals. In 8 patients, labral lesions were revealed at arthroscopy and were addressed using arthroscopic methods. RESULTS: The follow-up was from 24 to 33 months (26 mean). Patients without labral pathology (group A) and patients with labral lesions (group B) are discussed separately. Group A showed an increase in the mean Constant score at 6 months, but the scores reached a plateau after 6 months. Statistical analysis using 1-way analysis of variance (ANOVA) showed that the mean difference between the preoperative Constant score and the score at latest follow-up was statistically significant (P <.0001; 95% confidence interval, 13.4 to 31.6; standard error, 2.2). The rate of failure or complication was 16%. Three patients experienced recurrence of instability and another developed adhesive capsulitis. Overall, patient satisfaction was 83%. Group B showed an improvement in the Constant scores, and all 8 patients were satisfied. No clinical recurrence of the instability was seen in this group. However, 1 patient developed adhesive capsulitis. This group is too small to draw any statistically valid conclusions. CONCLUSIONS: The early results are encouraging. Postoperative physiotherapy is of paramount importance. Continued long-term follow-up of this relatively new technique is required to determine the failure rate increase that is likely to occur at longer time intervals.

Activities of Daily Living↗

PubMed2003

The antiproteinuric effect of losartan is systemic blood pressure dependent.

BACKGROUND: It has been suggested that high doses of angiotensin II receptor antagonists (AIIAs) may reduce proteinuria by a non-haemodynamic action additional to their effect on systemic blood pressure. METHODS: We tested this for the AIIA losartan using a prospective single-blind randomized design in patients with proteinuria (>1 g/24 h) due to non-diabetic chronic renal failure (stable creatinine clearance >20 ml/min) and mild to moderate hypertension (130/80 < blood pressure < 160/110 mmHg). Twenty-one patients were randomized into two groups: group A received losartan 50 mg daily for 4 weeks, then 100 mg daily for 4 weeks; group B received losartan 50 mg daily for 8 weeks. Twenty-four hour ambulatory blood pressure and renal parameters were measured at baseline and at 4 and 8 weeks of treatment. RESULTS: Overall there was a 7 +/- 2 mmHg fall (mean +/- SEM) in mean daytime systolic blood pressure at 4 weeks, and a 22 +/- 7% fall in protein/creatinine ratio (both P < 0.05), with no difference between groups A and B or between 4 and 8 weeks. These two changes were highly correlated (r = 0.64, P = 0.006, taking both groups together). Changes in diastolic pressure and in night-time systolic pressure did not reach statistical significance. Changes in renal plasma flow (measured by Tc 99m MAGIII), glomerular filtration rate and filtration fraction (measured by 51Cr EDTA) did not reach statistical significance, did not differ between the two groups and did not correlate with effects on proteinuria. CONCLUSION: This study provides no evidence that the effect of losartan on proteinuria has a non-haemodynamic component.

Adult↗

PubMed2003

Quantification of metabolic differences in the frontal brain of depressive patients and controls obtained by 1H-MRS at 3 Tesla.

RATIONALE AND OBJECTIVES: This study compared metabolic differences in the frontal brain of depressed patients versus age- and sex-matched controls using proton magnetic resonance spectroscopy and absolute quantification of metabolites (NAA, Cr, Cho, mI) at 3 Tesla. METHODS: Short-echo-time stimulated echo acquisition mode (TE/TM/TR=20/30/6000 milliseconds) was applied in the prefrontal region of 17 depressed patients and 17 age- and sex-matched controls. Metabolic ratios, ie, N-acetyl-aspartate/creatine (Cr), choline/Cr, and myo-inositol/Cr, and absolute concentrations (using internal water as a reference together with LCModel-based spectra fitting) were calculated and compared between groups and published reference data. RESULTS: Metabolic ratios showed significantly lower N-acetyl-aspartate/Cr (P = 0.016/0.006, left/right), choline/Cr (P = n.s./0.016), and myo-inositol/Cr (P = 0.022/0.026) for depressive patients versus controls. However, depressive patients showed significantly higher absolute concentrations of Cr (P = 0.017/0.0004) compared with controls with no differences in all other metabolites estimated. CONCLUSIONS: The authors demonstrate that absolute quantification of metabolite concentration is essential in properly identifying pathologic differences of brain metabolites in depression.

Adult↗

PubMed2002

The effect of phosphate loading on erythrocyte 2,3-bisphosphoglycerate levels.

BACKGROUND: Phosphate supplementation has been used in an effort to enhance athletic performance by increasing erythrocyte 2,3-bisphosphoglycerate levels ([2,3-BPG]) and hence improve oxygen offloading from haemoglobin. Claimed effects of phosphate loading upon both exercise performance and erythrocyte [2,3-BPG] are inconsistent, and the basis of any change in [2,3-BPG] is unknown. METHODS: We analysed plasma inorganic phosphate concentration ([P(i)]) and erythrocyte [P(i)] and [2,3-BPG] in venous blood samples from 12 healthy subjects. We re-examined a subset of five of these subjects after 7 days of phosphate loading. RESULTS: There were significant positive correlations between plasma [P(i)] and erythrocyte [P(i)] (r(2)=0.51, p=0.009) and between erythrocyte [P(i)] and [2,3-BPG] (r(2)=0.68, p<0.001). Following phosphate loading, there was a 30% increase in plasma [P(i)] (1.02+/-0.22 to 1.29+/-0.15 mmol/l (mean+/-S.D.), p=0.03) and a 25% increase in erythrocyte [2,3-BPG] (6.77+/-1.12 to 9.11+/-1.87 mmol/l cells, p=0.03). There is no relation between [2,3-BPG] and plasma [P(i)]. CONCLUSIONS: Phosphate loading increases both plasma and erythrocyte phosphate pools and the rise in [2,3-BPG] is probably a consequence of the rise in cell [P(i)].

2,3-Diphosphoglycerate↗

PubMedDate not supplied

Shoulder electromyography in multidirectional instability.

We studied shoulder muscle activity in multidirectional instability (MDI) and multidirectional laxity (MDL) of the shoulder, our hypothesis being that altered muscle activity plays a role in their pathogenesis. Six muscles (supraspinatus, infraspinatus, subscapularis, anterior deltoid, middle deltoid, and posterior deltoid) were investigated by use of intramuscular dual fine-wire electrodes in 7 normal shoulders, 5 MDL shoulders, and 6 MDI shoulders. Each subject performed 5 types of exercise (rotation in neutral, 45 degrees of abduction, 90 degrees of abduction, flexion/extension, and abduction/adduction) on an isokinetic muscle dynamometer at two rates, 90 degrees /s and 180 degrees /s. After filtering, rectification, and smoothing, the electromyography signal was normalized by using the peak voltage of the movement cycle. In subjects with MDI, compared with normal subjects, activity patterns of the anterior deltoid were different during rotation in neutral and 90 degrees of abduction, whereas those of the middle and posterior deltoid were different during rotation in 90 degrees of abduction. In subjects with MDL, the posterior deltoid showed increased activity compared with normal subjects during adduction. Activity patterns of the supraspinatus, infraspinatus, and subscapularis appeared similar in both groups. Dual fine-wire electromyography offers insight into the complex role of shoulder girdle muscle function in normal movement and in instability. Altered patterns of shoulder girdle muscle activity and imbalances in muscle forces support the theory that impaired coordination of shoulder girdle muscle activity and inefficiency of the dynamic stabilizers of the glenohumeral joint are involved in the etiology of MDI. Interestingly, the abnormalities are in the deltoid rather than the muscles of the rotator cuff.

Adult↗