PubMed Health⌕ Search

Biomedical subjects

M Kjaer

Publications and source records attributed to M Kjaer.

At least 37 records · Page 2Linked to original sources
PubMed2004

Interstitial muscle lactate, pyruvate and potassium dynamics in the trapezius muscle during repetitive low-force arm movements, measured with microdialysis.

AIM: Local muscle metabolic responses to repetitive low-force contractions and to intense static contractions were studied by microdialysis in humans. METHODS: Microdialysate and electromyography (EMG) were sampled from the trapezius muscle, mixed venous blood samples were taken and perceived exertion was rated (0-9) before and during 20 min of standardized repetitive arm movement (REP), 60 min recovery (R1), and 10 min 90 degrees sustained arm position (SUS) at 20% maximum voluntary contraction, followed by 60 min recovery (R2) in six healthy male participants (28-33 years). RESULTS: Average muscle activity was 8 +/- 2% of EMGmax-RMS (mean +/-SEM) during REP and 22 +/- 5% of EMGmax-RMS during SUS. Perceived exertion increased from 0 to 3.2 +/- 0.5 during REP and from 0 to 8.5 +/- 0.3 during SUS. During REP interstitial muscle lactate increased from 2.1 +/- 0.2 to 2.9 +/- 0.2 mmol L(-1) (P < 0.001) and returned to the baseline level during R1, while dialysate [K+] increased from 3.8 +/- 0.2 to 4.7 +/- 0.2 mmol L(-1) (P < 0.002) and returned to 3.8 +/- 0.2 mmol L(-1) during R1. In contrast, plasma lactate and [K+] remained unchanged. During SUS interstitial muscle lactate increased from 2.3 +/- 0.2 to 3.3 +/- 0.3 mmol L(-1) (P < 0.003), increased further to 6.5 +/- 1.3 mmol L(-1) post-exercise (P < 0.001) and returned to baseline levels during R2. Dialysate [K+] increased from 3.9 +/- 0.2 to 4.6 +/- 0.2 mmol L(-1) (P < 0.05) and returned to baseline level during R2. Plasma lactate increased significantly during SUS whereas plasma [K+] was unchanged. During REP and SUS interstitial pyruvate was unchanged but increased in the post-exercise period proportional to the exercise intensity. CONCLUSIONS: The microdialysis technique was effective in revealing muscle metabolic events that were not found systemically. Furthermore, the trapezius muscle showed an anaerobic metabolism during low-force contraction, which could indicate inhomogeneous muscle activation.

Adult↗
PubMed2004

Regulation of blood flow by prostaglandins.

Prostaglandins (PGs) belong to the family of prostanoids together with thromboxanes and are produced mainly from arachadonic acid by the enzyme cyclooxygenase. PGs are known to stimulate platelet aggregation, mediate inflammation and edema, play a role in bone metabolism and in biological adaptation of connective tissues e.g. tendon. This review covers the role of PG for mediating tissue blood flow at rest and during increases in metabolic demand such as exercise and reactive hyperaemia. There is strong evidence that PGs contribute to elevate blood flow at rest and during reactive hyperaemia in a variety of tissues. Their role for regulating the large increases in muscle blood flow during exercise is less clear which may be explained by redundant mechanisms. Several interactions are known to exist between specific vasodilator substances, and therefore PGs can act in synergy with other substances and contribute to functional hyperaemia. Furthermore, there is evidence for differential, tissue-specific influences of PGs where their influence on blood flow during exercise may be profound.

Animals↗
PubMed2003

The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men.

The expression of two isoforms of insulin-like growth factor-I (IGF-I): mechano growth factor (MGF) and IGF-IEa were studied in muscle in response to growth hormone (GH) administration with and without resistance training in healthy elderly men. A third isoform, IGF-IEb was also investigated in response to resistance training only. The subjects (age 74 +/- 1 years, mean +/- S.E.M) were assigned to either resistance training with placebo, resistance training combined with GH administration or GH administration alone. Real-time quantitative RT-PCR was used to determine mRNA levels in biopsies from the vastus lateralis muscle at baseline, after 5 and 12 weeks in the three groups. GH administration did not change MGF mRNA at 5 weeks, but significantly increased IGF-IEa mRNA (237%). After 12 weeks, MGF mRNA was significantly increased (80%) compared to baseline. Five weeks of resistance training significantly increased the mRNA expression of MGF (163%), IGF-IEa (68%) and IGF-IEb (75%). No further changes were observed after 12 weeks. However, after 5 weeks of training combined with GH treatment, MGF mRNA increased significantly (456%) and IGF-IEa mRNA by (167%). No further significant changes were noted at 12 weeks. The data suggest that when mechanical loading in the form of resistance training is combined with GH, MGF mRNA levels are enhanced. This may reflect an overall up-regulation of transcription of the IGF-I gene prior to splicing.

Aged↗
PubMed2003

Physical exercise can influence local levels of matrix metalloproteinases and their inhibitors in tendon-related connective tissue.

Microdialysis studies indicate that mechanical loading of human tendon tissue during exercise or training can affect local synthesis and degradation of type I collagen. Degradation of collagen and other extracellular matrix proteins is controlled by an interplay between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). However, it is unknown whether local levels of MMPs and TIMPs are affected by tendon loading in humans in vivo. In the present experiment, six healthy young men performed 1 h of uphill (3%) treadmill running. Dialysate was collected from microdialysis probes (placed in the peritendinous tissue immediately anterior to the Achilles tendon) before, immediately after, 1 day after, and 3 days after an exercise bout. MMP-2 and MMP-9 were measured in dialysate by gelatin zymography, and amounts were quantified by densitometry in relation to total protein in the dialysate. TIMP-1 and TIMP-2 were analyzed by reverse gelatin zymography and semiquantitated visually. Pro-MMP-9 increased markedly after exercise and remained high for 3 days after exercise. Pro-MMP-2 dropped from the basal level immediately after exercise and remained low 1 day after exercise but was slightly elevated 3 days after exercise. The MMP-2 inhibitory activity of TIMP-1 was clearly elevated 1 and 3 days after exercise, and the MMP-2 inhibitory activity of TIMP-2 rose 1 day after loading. The present findings demonstrate enhanced interstitial amounts of MMPs and TIMPs after exercise in the human peritendinous tissue in vivo, and the magnitude and time pattern of these changes may well indicate that MMPs and TIMPs are playing a role in extracellular matrix adaptation to exercise in tendon tissue.

Achilles Tendon↗
PubMed2003

Effect of habitual running on human Achilles tendon load-deformation properties and cross-sectional area.

Whether the cross-sectional area (CSA) and mechanical properties of the human Achilles tendon change in response to habitual exercise remains largely unexplored. The present study evaluated the CSA and contraction-induced displacement of the aponeurosis-tendon complex of the triceps surae in 11 untrained subjects before (tests 1 and 2) and after (test 3) approximately 9 mo of regular running ( approximately 78 training sessions). Displacement of the tendon-aponeurosis complex obtained by ultrasonography; electromyography of the gastrocnemius, soleus, and dorsiflexor muscles; and joint angular rotation were recorded during graded isometric plantarflexion ramps. Tendon CSA and moment arm were measured by using MRI, and tendon force was calculated from joint moments and tendon moment arm. A treadmill test was used to determine submaximal oxygen consumption (Vo2) at a given speed and maximal Vo2. The total running duration was approximately 43 h, distributed over 34 wk. Maximal Vo2 increased 8.6% (P < 0.01), and submaximal Vo2 decreased 6.2% (P < 0.05). Tendon-aponeurosis displacement during maximal voluntary contraction was unchanged (tests 1-3, 5.2 +/- 0.6, 5.2 +/- 0.5, and 5.3 +/- 0.4 mm, respectively) and yielded a structural stiffness of 365 +/- 50, 358 +/- 40, and 384 +/- 52 N/mm for tests 1-3, respectively (P > 0.05). Tendon CSA also remained unchanged (tests 1-3, 34.2 +/- 2.2, 33.9 +/- 2.2, and 33.8 +/- 2.1 mm2, respectively). In conclusion, a total training stimulus of approximately 9 mo of running in previously untrained subjects was adequate to induce significant cardiovascular improvements, although it did not result in any changes in the mechanical properties of the triceps surea tendon-aponeurosis complex or in the dimensions of Achilles tendon.

Achilles Tendon↗
PubMed2003

Cyclo-oxygenase-2 mediated prostaglandin release regulates blood flow in connective tissue during mechanical loading in humans.

Mechanical loading is known to increase connective tissue blood flow of human tendons and to cause local release of vasodilatory substances. The present study investigated the importance of prostaglandins (PG) formed by cyclo-oxygenase isoforms (COX-1 and 2) for the exercise-related increase in blood flow in connective tissue. Healthy individuals (n = 24, age: 23-31 years) underwent 30 min of intermittent, isometric, plantarflexion with both calf muscles either without (n = 6, Control, C) or with blockade of PG formation, either COX-2 specific (n = 10, Celecoxib 2 x 100 mg day-1 for 3 days prior to the experiment) or COX unspecific (n = 8, indomethacin 100 mg (12 and 1 h pre-experiment) and acetyl salicylic acid 500 mg day-1 for 3 days pre-experiment). Prostaglandin E2 (PGE2) concentration was determined by microdialysis and blood flow by 133Xe washout. In C, interstitial PGE2 rose from (0.8 +/- 0.2 (rest) to 1.4 +/- 0.5 ng ml-1 (exercise), P < 0.05), whereas during unspecific COX inhibition, tissue PGE2 was completely inhibited at rest and during exercise. COX-2 specific blockade did not inhibit tissue PGE2 at rest, but totally abolished the exercise induced increase. Blood flow was similar in the three groups at rest (P > 0.05), whereas the increase in flow with exercise was reduced by 35 and 43 % with COX-2 specific blockade (3.2 +/- 0.7 to 6.1 +/- 1.5 ml (100 g tissue)-1 min-1 or COX unspecific blockade (3.0 +/- 0.8 to 7.6 +/- 1.6), respectively, compared to C (2.7 +/- 0.8 to 10.2 +/- 2.0)(P < 0.05). The findings indicate that COX-2 specific mechanisms are responsible for the exercise-induced increase in prostaglandin synthesis, and that increase in tissue prostaglandin plays an important role for blood flow in peritendinous connective tissue during physical loading in vivo.

Achilles Tendon↗
PubMed2003

Combined epirubicin and vinorelbine as first-line therapy in metastatic breast cancer: a pilot study performed by the Danish Breast Cancer Cooperative Group.

This pilot study investigated the tolerability and efficacy of increasing doses of epirubicin and vinorelbine as first-line chemotherapy for metastatic breast cancer. Acute toxicity was manageable at all dose levels for combinations of epirubicin 60-90 mg/m2 on day 1 and vinorelbine 15-25 mg/m2 on days 1 and 8 repeated every 3 weeks. Myelotoxicity was the most frequent toxic event, with a significant increase in grade 4 leukopenia from 0% at dose level 1 (60+15 mg/m2) to 26% at dose level 6 (90+25 mg/m2). Signs of acute or chronic cardiotoxicity grades 2-4 were seen in 15% of the patients and included arrhythmia and decreased function. No significant association was established between dose and nonhematological toxicity. Objective responses were observed in 49 of the 99 evaluable patients (49.5%, 95% CI 39.9-59.2), 18 being complete and 31 partial responses. Responses were observed at all six dose levels. In conclusion, acute toxicity was manageable at all dose levels for combinations of epirubicin 60-90 mg/m2 on day 1 and vinorelbine 15-25 mg/m2 on days 1 and 8. In the treatment of advanced breast cancer, improvement of the antitumor efficacy by the addition of vinorelbine to epirubicin remains to be demonstrated in a randomized phase III trial.

Adult↗
PubMed2003

Measuring mechanical properties of the vastus lateralis tendon-aponeurosis complex in vivo by ultrasound imaging.

The mechanical properties of the human vastus lateralis (VL) tendon-aponeurosis complex were investigated in eight male subjects. Knee extensor force, knee joint angle, and corresponding longitudinal VL aponeurosis displacement were monitored synchronously during graded (10-s) maximal isometric knee extension contractions. Displacement observed during isometric conditions may be regarded as an expression of deformation in the tissues distal to the measurement site. Furthermore, aponeurosis displacement was measured during passive knee extension (90-75 degrees degrees ), and used to correct displacement values obtained during active contraction for joint angular motion. The passive trial yielded a highly linear relationship between aponeurosis displacement and joint angular motion (r2 = 0.998 +/- 0.002) with a mean correction factor of 0.41 +/- 0.10 mm/degree. Maximal knee extensor force was 5834 +/- 1341 N with a corresponding VL aponeurosis displacement of 12.7 +/- 2.5 mm, while correcting for joint angular motion reduced maximal displacement approximately 9% (to 11.6 +/- 2.5 mm, P < 0.005) (data presented as means +/- SD). Two separate graded contraction trials were performed, and no between-trial differences were observed in either maximal force or maximal displacement. Between trial coefficient of determination and CV for maximal force and maximal displacement were r2 = 0.97, CV = 2.9% and r2 = 0.92, CV = 4.6%, respectively, indicating intra-day reproducibility of measurements. These data demonstrate that when applying the newly established ultrasound-based method of investigating quadriceps connective tissue mechanical properties, maximal isometric contraction is inevitably associated with some joint angular motion that significantly influences the calculations.

Biomechanical Phenomena↗
PubMed2003

Tendon properties in relation to muscular activity and physical training.

Movement is caused by force transmission from contracting muscles to bone via tendon. The collagen structure of tendon is organized in a very hierarchical manner. The collagen fibril is considered the basic force-transmitting unit of tendon, and it is embedded in a hydrophilic extracellular matrix of proteoglycans, glycoproteins and glycosaminoglycans. It has recently been shown in human peritendinous tissue is more metabolically active in response to activity than previously thought, although it remains to be established, if the level of activity influences affects fibril diameter and/or total tendon cross-sectional area. Moreover, it cannot be unequivocally concluded that tendon adaptation to physical activity is one of a quantitative and/or qualitative nature. The currently available information is almost exclusively obtained from animal data, however, techniques such as microdialysis for tendon metabolism and ultrasound combined with MRI for tendon mechanical properties has already provided information on human tendon behavior, and is likely to further add to our understanding of how tendon adapt to physical activity. This review will address the structure and function of tendon, and the current knowledge of how tendons respond to activity with respect to biomechanical properties.

Animals↗
PubMed2003

Differential strain patterns of the human gastrocnemius aponeurosis and free tendon, in vivo.

AIM: The mechanical characteristics of the human free tendon and aponeurosis, in vivo, remains largely unknown. The present study evaluated the longitudinal displacement of the separate free Achilles tendon and distal (deep) aponeurosis of the medial gastrocnemius muscle during voluntary isometric contraction. METHODS: Ultrasonography-obtained displacement of the free tendon and tendon-aponeurosis complex, electromyography of the gastrocnemius, soleus, and dorsiflexor muscles, and joint angular rotation were recorded during isometric plantarflexion (n = 5). Tendon cross-sectional area, moment arm and segment lengths (L(o)) were measured using magnetic resonance imaging. Tendon force was calculated from joint moments and tendon moment arm, and stress was obtained by dividing force by cross-sectional area. The difference between the free tendon and tendon-aponeurosis complex deformation yielded separate distal aponeurosis deformation. Longitudinal aponeurosis and tendon strain were obtained from the deformations normalized to segment lengths. RESULTS: At a common tendon force of 2641 +/- 306 N, the respective deformation and Lo were 5.85 +/- 0.85 and 74 +/- 0.8 mm for the free tendon and 2.12 +/- 0.64 and 145 +/- 1.3 mm for the distal aponeurosis, P < 0.05. Longitudinal strain was 8.0 +/- 1.2% for the tendon and 1.4 +/- 0.4% for the aponeurosis, P < 0.01. Stiffness and stored energy was 759 +/- 132 N mm(-1) and 6.14 +/- 1.89 J, respectively, for the free tendon. Cross-sectional area of the Achilles tendon was 73 +/- 4 mm2, yielding a stress of 36.5 +/- 4.6 MPa and Young's modulus of 788 +/- 181 MPa. CONCLUSION: The free Achilles tendon demonstrates greater strain compared with that of the distal (deep) aponeurosis during voluntary isometric contraction, which suggests that separate functional roles may exist during in vivo force transmission.

Achilles Tendon↗
PubMed2002

Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans.

Bradykinin is known to cause vasodilatation in resistance vessels and may, together with adenosine, be an important regulator of tissue blood flow during exercise. Whether tissue concentrations of bradykinin change with exercise in skeletal muscle and tendon-related connective tissue has not yet been established. Microdialysis (molecular mass cut-off 5 kDa) was performed simultaneously in calf muscle and peritendinous Achilles tissue at rest and during 10 min periods of incremental (0.75 W, 2 W, 3.5 W and 4.75 W) dynamic plantar flexion exercise in 10 healthy individuals (mean age 27 years, range 22-33 years). Interstitial bradykinin and adenosine concentrations were determined using an internal reference to determine relative recovery ([2,3,prolyl-3,4-(3)H(N)]-bradykinin and [2-(3)H]-adenosine). Bradykinin and adenosine recovery were closely related and in the range of 30-50 %. The interstitial concentration of bradykinin rose in response to exercise both in skeletal muscle (from 23.1 +/- 4.9 nmol l(-1) to 110.5 +/- 37.9 nmol l(-1); P < 0.05) and in the peritendinous tissue (from 27.7 +/- 7.8 nmol l(-1) to 105.0 +/- 37.9 nmol l(-1); P < 0.05). In parallel, the adenosine concentration increased both in muscle (from 0.48 +/- 0.07 micromol l(-1) to 1.59 +/- 0.35 micromol l(-1); P < 0.05) and around the tendon (from 0.33 +/- 0.03 micromol l(-1) to 0.86 +/- 0.16 micromol l(-1); P < 0.05). In conclusion, the data show that muscular activity increases the interstitial concentrations of bradykinin and adenosine in both skeletal muscle and the connective tissue around its adjacent tendon. These findings support a role for bradykinin and adenosine in exercise-induced hyperaemia in skeletal muscle and suggest that bradykinin and adenosine are potential regulators of blood flow in peritendinous tissue.

Achilles Tendon↗
PubMed2002

Collagen fibril size and crimp morphology in ruptured and intact Achilles tendons.

The present study examined the hypothesis that collagen fibril diameter and crimp angle in ruptured human Achilles tendons differed from that of intact ones. Tissue samples were obtained from the central core (distal core) and the posterior periphery (distal superficial) at the rupture site, and the proximally intact (proximal superficial) part of the tendon in 10 subjects (38+/-8 years) with a complete tendon rupture. For comparisons corresponding tissue samples were procured from age (38+/-7 years) and gender matched intact Achilles tendons during routine forensic autopsy. The cross-sectional area density and diameter distribution of fibrils were analyzed using stereological techniques of digitized electron microscopy biopsy cross-sections, while crimp angle was measured by the changing banding pattern of collagen fibers when rotated between crossed polars. Nine of 10 persons with tendon ruptures reported that the injury did not occur during exceedingly large forces, and none experienced any symptoms in the days or months prior to the injury. Fibril diameter distribution showed no region-specific differences in either the ruptured or intact tendons for either group. However, in the distal core there were fewer fibrils in the ruptured compared to the intact tendons in 60-150 nm range, P<0.01. Similarly, in the distal superficial portion there were fewer fibrils in the ruptured compared to the intact tendons in the 90-120 nm range, 2P<0.05, while there were no differences in the proximal superficial tendons. Crimp angle did not display any region-specific differences, or any difference between the rupture and intact tendons. In conclusion, these data suggest that although crimp morphology is unchanged there appears to be a site-specific loss of larger fibrils in the core and periphery of the Achilles tendon rupture site. Moreover, the lack of symptoms prior to the rupture suggests that clinical tendinopathy is not an etiological factor in complete tendon ruptures.

Achilles Tendon↗
PubMed2002

Load-displacement properties of the human triceps surae aponeurosis and tendon in runners and non-runners.

The load-displacement and stress-strain characteristics of the human triceps surae tendon and aponeurosis, in vivo, was examined during graded maximal voluntary plantarflexion efforts in runners who trained 80 km/ week or more and age-matched non-runners. Synchronous real-time ultrasonography of triceps surae tendon and aponeurosis displacement, electromyography of the gastrocnemius, soleus and dorsiflexor muscles, and joint angular rotation were obtained. Tendon cross-sectional area and ankle joint moment arm were obtained from magnetic resonance imaging. Tensile tendon force was calculated from the joint moments and tendon moment arm and stress was obtained by dividing force by cross-sectional area. Strain was obtained from the displacements normalized to tendon length. Antagonist coactivation and small amounts of ankle joint rotation significantly affected tensile tendon force and aponeurosis and tendon displacement, respectively (P < 0.01). Plantarflexion moment was similar in runners (138 +/- 27 Nm, mean +/- SEM) and non-runners (142 +/- 17 Nm). Tendon moment arm was alike in non-runner (58.3 +/- 0.2 mm) and runners (55.1 +/- 0.1 mm). Similarly, there was no difference in tendon tensile force between runners (2633 +/- 465 N) and non-runners (2556 +/- 401 N). The cross-sectional area of the Achilles tendon was larger in runners (95 +/- 3 mm2) than non-runners (73 +/- 3 mm(2)) (P < 0.01). The load-deformation data yielded similar stiffness (runners 306 +/- 61 N/mm, non-runners 319 +/- 42 N/mm). The maximal strain and stress was 4.9 +/- 0.8% and 38.2 +/- 9.8 MPa in non-runners and 4.1 +/- 0.8% and 26.3 +/- 5.1 MPa in runners. The larger tendon cross-sectional area in trained runners suggests that chronic exposure to repetitive loading has resulted in a tissue adaptation.

Achilles Tendon↗
PubMed2002

Proprioception in poor- and well-functioning anterior cruciate ligament deficient patients.

The aim of this study was to examine proprioception with and without muscle tension and knee function in two groups of chronic (> 1 year post-injury) patients with deficient anterior cruciate ligaments with distinctly different functioning levels. The well (WF) and poor functioning (PF) group was defined as those with a Tegner/Lysholm score equal to or greater than 6/95 (WF, n = 7), and equal to or less than 4/83 (PF, n = 7), respectively. Clinical examination included a Lachman, and a Pivot shift test, as well as a KT2000 arthrometer assessment. Single and triple hop tests assessed one-legged performance. Proprioception was measured as threshold of passive movement detection, and as the ability to reproduce flexion angles with (20% and 50% MVC) and without muscle tension. Mean Tegner/Lysholm scores were: WF: 7 (range 6-8)/98 (range 95-100), PF: 2 (range 1-4)/71 (range 62-80). There were significant differences between the Pivot shift tests of the groups (p = 0.01). The laxity (KT2000) assessment yielded a significant (3 mm, p < 0.05) side-to-side difference in both groups. One-leg hop tests yielded no side-to-side differences in any of the groups or between the groups. There were no significant differences between the groups in any of the proprioceptive tests, except in one of the angle reproduction tests with muscle tension (20%, p < 0.05). WF had larger mean errors than PF. There was not found any side-to-side difference in any of the proprioceptive tests, except in one of the angle reproduction tests with muscle tension (WF, 20%, p < 0.05). In conclusion, these data suggest that subjects with long standing anterior cruciate ligament deficiency in the present study did not have a knee joint proprioceptive deficit as measured by some commonly accepted methods. There was no difference in proprioception between the two groups despite their markedly different function levels and pivot shift evaluated knee laxity.

Activities of Daily Living↗
PubMed2002

Irinotecan combined with bolus 5-fluorouracil and folinic acid Nordic schedule as first-line therapy in advanced colorectal cancer.

BACKGROUND: This multicentre phase II study evaluated the efficacy and safety of irinotecan combined with the Nordic schedule of 5-fluorouracil (5-FU) and folinic acid (FA) as first-line therapy in patients with advanced colorectal cancer. PATIENTS AND METHODS: Seventy-four patients with measurable disease and a WHO performance status of 2 or less were treated with irinotecan 210 mg/m(2) as a 30-90 min intravenous infusion on day 1, followed by 5-FU 500 mg/m(2) and FA 60 mg/m(2) bolus on days 1 and 2, every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was the objective response rate. RESULTS: Twenty-nine out of 68 evaluable patients achieved a complete (n = 7) or partial (n = 22) response, leading to an overall response rate of 43% [95% confidence interval (CI) 31% to 55%]. The median duration of response was 10 months. The estimated median time to progression and survival were 6.4 months (95% CI 5.4-9.0) and 15.6 months (95% CI 13.3-19.0), respectively, in the intention-to-treat population. A total of 860 cycles were administered to 74 patients. Neutropenia was the main adverse event with grade 3-4 toxicity in 66% of patients and 17.5% of cycles. Grade 3-4 non-haematological toxicities were infrequent and included diarrhoea in 16% of patients and 2% of cycles and nausea/vomiting in 10% of patients and 1% of cycles. CONCLUSIONS: Irinotecan combined with the bolus Nordic schedule of 5-FU/FA is active in advanced colorectal cancer with an easily managed safety profile which ensures good schedule compliance. The low incidence of grade 3-4 non-haematological toxicity justifies the further evaluation of this combination in the context of randomised clinical trials.

Adenocarcinoma↗
PubMed2001

Muscle oxygen uptake and energy turnover during dynamic exercise at different contraction frequencies in humans.

1. It has been established that pulmonary oxygen uptake is greater during cycle exercise in humans at high compared to low contraction frequencies. However, it is unclear whether this is due to more work being performed at the high frequencies and whether the energy turnover of the working muscles is higher. The present study tested the hypothesis that human skeletal muscle oxygen uptake and energy turnover are elevated during exercise at high compared to low contraction frequency when the total power output is the same. 2. Seven subjects performed single-leg dynamic knee-extensor exercise for 10 min at contraction frequencies of 60 and 100 r.p.m. where the total power output (comprising the sum of external and internal power output) was matched between frequencies (54 +/- 5 vs. 56 +/- 5 W; mean +/- S.E.M.). Muscle oxygen uptake was determined from measurements of thigh blood flow and femoral arterial - venous differences for oxygen content (a-v O(2) diff). Anaerobic energy turnover was estimated from measurements of lactate release and muscle lactate accumulation as well as muscle ATP and phosphocreatine (PCr) utilisation based on analysis of muscle biopsies obtained before and after each exercise bout. 3. Whilst a-v O(2) diff was the same between contraction frequencies during exercise, thigh blood flow was higher (P < 0.05) at 100 compared to 60 r.p.m. Thus, muscle V(O2) was higher (P < 0.05) during exercise at 100 r.p.m. Muscle V(O2) increased (P < 0.05) by 0.06 +/- 0.03 (12 %) and 0.09 +/- 0.03 l min(-1) (14 %) from the third minute to the end of exercise at 60 and 100 r.p.m., respectively, but there was no difference between the two frequencies. 4. Muscle PCr decreased by 8.1 +/- 1.7 and 9.1 +/- 2.0 mmol (kg wet wt)(-1), and muscle lactate increased to 6.8 +/- 2.1 and 9.8 +/- 2.5 mmol (kg wet wt)(-1) during exercise at 60 and 100 r.p.m., respectively. The total release of lactate during exercise was 48.7 +/- 8.8 and 64.3 +/- 10.6 mmol at 60 and 100 r.p.m. (not significant, NS). The total anaerobic ATP production was 47 +/- 8 and 61 +/- 12 mmol kg(-1), respectively (NS). 5. Muscle temperature increased (P < 0.05) from 35.8 +/- 0.3 to 38.2 +/- 0.2 degrees C at 60 r.p.m. and from 35.9 +/- 0.3 to 38.4 +/- 0.3 degrees C at 100 r.p.m. Between 1 and 7 min muscle temperature was higher (P < 0.05) at 100 compared to 60 r.p.m. 6. The estimated mean rate of energy turnover during exercise was higher (P < 0.05) at 100 compared to 60 r.p.m. (238 +/- 16 vs. 194 +/- 11 J s(-1)). Thus, mechanical efficiency was lower (P < 0.05) at 100 r.p.m. (24 +/- 2 %) compared to 60 r.p.m. (28 +/- 3 %). Correspondingly, efficiency expressed as work per mol ATP was lower (P < 0.05) at 100 than at 60 r.p.m. (22.5 +/- 2.1 vs. 26.5 +/- 2.5 J (mmol ATP)(-1)). 7. The present study showed that muscle oxygen uptake and energy turnover are elevated during dynamic contractions at a frequency of 100 compared with 60 r.p.m. It was also observed that muscle oxygen uptake increased as exercise progressed in a manner that was not solely related to the increase in muscle temperature and lactate accumulation.

Adenosine Triphosphate↗
PubMed2001

Role of the sympathoadrenergic system in adipose tissue metabolism during exercise in humans.

1. The relative roles of sympathetic nerve activity and circulating catecholamines for adipose tissue lipolysis during exercise are not known. 2. Seven paraplegic spinal cord injured (SCI, injury level T3-T5) and seven healthy control subjects were studied by microdialysis and (133)xenon washout in clavicular (Cl) and in umbilical (Um) (sympathetically decentralized in SCI) subcutaneous adipose tissue during 1 h of arm cycling exercise at approximately 60 % of the peak rate of oxygen uptake. 3. During exercise, adipose tissue blood flow (ATBF) and interstitial glycerol, lactate and noradrenaline concentrations increased significantly in both groups. Plasma catecholamine levels increased significantly less with exercise in SCI than in healthy subjects. The exercise-induced increase in interstitial glycerol concentration in subcutaneous adipose tissue was significantly lower in SCI compared with healthy subjects (SCI: 25 +/- 12 % (Cl), 36 +/- 20 % (Um); healthy: 60 +/- 17 % (Cl), 147 +/- 45 % (Um)) and the increase in ATBF was significantly lower (Cl) or similar (Um) in SCI compared with healthy subjects (SCI: 1.2 +/- 0.3 ml (100 g)(-1) min(-1) (Cl), 1.0 +/- 0.3 ml (100 g)(-1) min(-1) (Um); healthy: 2.8 +/- 0.7 ml (100 g)(-1) min(-1) (Cl), 0.6 +/- 0.3 ml (100 g)(-1) min(-1) (Um)). Accordingly, in both adipose tissues lipolysis increased less in SCI compared with healthy subjects, indicating that circulating catecholamines are important for the exercise-induced increase in subcutaneous adipose tissue lipolysis. In SCI subjects, the exercise-induced increase in subcutaneous adipose tissue lipolysis was not lower in decentralized than in sympathetically innervated adipose tissue. During exercise the interstitial noradrenaline and adrenaline concentrations were lower in SCI compared with healthy subjects (P < 0.05) and always lower than arterial plasma catecholamine concentrations (P < 0.05). 4. It is concluded that circulating catecholamines are important for the exercise-induced increase in subcutaneous adipose tissue lipolysis while sympathetic nerve activity is not.

3-Hydroxybutyric Acid↗