Value of routine intraoperative frozen sections of proximal bile duct margins in perihilar cholangiocarcinoma, a retrospective multicenter and matched case-control study.

BACKGROUND: Currently, the potential benefits of additional resection after positive proximal intraoperative frozen sections (IFS) in perihilar cholangiocarcinoma (pCCA) on residual disease and oncological outcome remain uncertain. Therefore, the aim of this study is to investigate the number of R0 resections after additional resection of a positive proximal IFS and the influence of additional resections on overall survival (OS) in patients with pCCA. MATERIALS AND METHODS: A retrospective, multicenter, matched case-control study was performed, including patients undergoing resection for pCCA between 2000 and 2019 at three tertiary centers. Primary outcome was the number of achieved 'additional' R0 resections. Secondary outcomes were OS, recurrence, severe morbidity and mortality. RESULTS: Forty-four out of 328 patients undergoing resection for pCCA had a positive proximal IFS. An additional resection was performed in 35 out of 44 (79.5%) patients, which was negative in 24 (68.6%) patients. Nevertheless, seven out of these 24 patients were eventually classified as R1 resection due to other positive resection margins. Therefore, 17 (48.6%) patients could be classified as "true" R0 resection after additional resection. Ninety-day mortality after R1 resections was high (25%) and strongly influenced OS. After correction for 90-day mortality, median OS after negative additional resection was 33 months (95%CI:29.5-36.5) compared to 30 months (95%CI:24.4-35.6) after initial R1 (P = 0.875) and 46 months (95%CI:32.7-59.3) after initial R0 (P = 0.348). CONCLUSION: There were only 17 patients (out of a total of 328 patients) that potentially benefitted from routine IFS. Additional resection for a positive IFS leading to R0 resection was not associated with improved long-term survival.

Extended Resections for Advanced Gallbladder Cancer: Results from a Nationwide Cohort Study.

BACKGROUND: Extended resections (i.e., major hepatectomy and/or pancreatoduodenectomy) are rarely performed for gallbladder cancer (GBC) because outcomes remain inconclusive. Data regarding extended resections from Western centers are sparse. This Dutch, multicenter cohort study analyzed the outcomes of patients who underwent extended resections for locally advanced GBC. METHODS: Patients with GBC who underwent extended resection with curative intent between January 2000 and September 2018 were identified from the Netherlands Cancer Registry. Extended resection was defined as a major hepatectomy (resection of ≥ 3 liver segments), a pancreatoduodenectomy, or both. Treatment and survival data were obtained. Postoperative morbidity, mortality, survival, and characteristics of short- and long-term survivors were assessed. RESULTS: The study included 33 patients. For 16 of the patients, R0 resection margins were achieved. Major postoperative complications (Clavien Dindo ≥ 3A) occurred for 19 patients, and 4 patients experienced postoperative mortality within 90 days. Recurrence occurred for 24 patients. The median overall survival (OS) was 12.8 months (95% confidence interval, 6.5-19.0 months). A 2-year survival period was achieved for 10 patients (30%) and a 5-year survival period for 5 patients (15%). Common bile duct, liver, perineural and perivascular invasion and jaundice were associated with reduced survival. All three recurrence-free patients had R0 resection margins and no liver invasion. CONCLUSION: The median OS after extended resections for advanced GBC was 12.8 months in this cohort. Although postoperative morbidity and mortality were significant, long-term survival (≥ 2 years) was achieved in a subset of patients. Therefore, GBC requiring major surgery does not preclude long-term survival, and a subgroup of patients benefit from surgery.

The pharmacokinetics and dosing of oral 4-methylumbelliferone for inhibition of hyaluronan synthesis in mice.

Recently, there has been considerable interest in using 4-methylumbelliferone (4-MU) to inhibit hyaluronan (HA) synthesis in mouse models of cancer, autoimmunity and a variety of other inflammatory disorders where HA has been implicated in disease pathogenesis. In order to facilitate future studies in this area, we have examined the dosing, treatment route, treatment duration and metabolism of 4-MU in both C57BL/6 and BALB/c mice. Mice fed chow containing 5% 4-MU, a dose calculated to deliver 250 mg/mouse/day, initially lose substantial weight but typically resume normal weight gain after 1 week. It also takes up to a week to see a reduction in serum HA in these animals, indicating that at least a 1-week loading period on the drug is required for most protocols. At steady state, more than 90% of the drug is present in plasma as the glucuronidated metabolite 4-methylumbelliferyl glucuronide (4-MUG), with the sulphated metabolite, 4-methylumbelliferyl sulphate (4-MUS) comprising most of the remainder. Chow containing 5% but not 0·65% 4-MU was effective at preventing disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis, as well as in the DORmO mouse model of autoimmune diabetes. While oral 4-MU was effective at preventing EAE, daily intraperitoneal injections of 4-MU were not. Factors potentially affecting 4-MU uptake and plasma concentrations in mice include its taste, short half-life and low bioavailability. These studies provide a practical resource for implementing oral 4-MU treatment protocols in mice.

Resistance training in cancer survivors: a systematic review.

This systematic review summarizes the research of previous studies that used resistance training in the post-treatment phase of cancer patients with a focus on methodological quality, training methods and physical outcome measures. We found twenty-four studies (10 RCTs, 4 controlled clinical trials and 10 uncontrolled trials) that met all inclusion criteria. The studies were of moderate methodological quality. The majority of studies involved breast cancer patients (54%), followed by prostate cancer patients (13%). Most studies used a combination of resistance and aerobic training, which was mostly supervised. Resistance training involved large muscle groups, with 1-3 sets of 8-12 repetitions. The duration of the resistance training programs varied from 3-24 weeks, with a training frequency of 1-5 sessions per week. The training intensity ranged from 25% to 85% of the one-repetition maximum. Overall, positive training effects were observed for cardiopulmonary and muscle function, with significant increases in peak oxygen uptake (range: 6-39%), and in the one-repetition maximum (range: 11-110%). In general, there were no effects of training on body composition, endocrine and immune function, and haematological variables. No adverse effects of the resistance training were reported. Based upon these results, we recommend to incorporate resistance training in cancer rehabilitation programmes.

Brisk walking compared with an individualised medical fitness programme for patients with type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: Structured exercise is considered a cornerstone in type 2 diabetes treatment. However, adherence to combined resistance and endurance type exercise or medical fitness intervention programmes is generally poor. Group-based brisk walking may represent an attractive alternative, but its long-term efficacy as compared with an individualised approach such as medical fitness intervention programmes is unknown. We compared the clinical benefits of a 12-month exercise intervention programme consisting of either brisk walking or a medical fitness programme in type 2 diabetes patients. METHODS: We randomised 92 type 2 diabetes patients (60 +/- 9 years old) to either three times a week of 60 min brisk walking (n = 49) or medical fitness programme (n = 43). Primary outcome was the difference in changes in HbA1c values at 12 months. Secondary outcomes were differences in changes in blood pressure, plasma lipid concentrations, insulin sensitivity, body composition, physical fitness, programme adherence rate and health-related quality of life. RESULTS: After 12 months, 18 brisk walking and 19 medical fitness participants were still actively participating. In both programmes, 50 and 25% of the dropout was attributed to overuse injuries and lack of motivation, respectively. Intention-to-treat analyses showed no important differences between brisk walking and medical fitness programme in primary or secondary outcome variables. CONCLUSIONS/INTERPRETATION: The prescription of group-based brisk walking represents an equally effective intervention to modulate glycaemic control and cardiovascular risk profile in type 2 diabetes patients when compared with more individualised medical fitness programmes. Future exercise intervention programmes should anticipate the high attrition rate due to overuse injuries and motivation problems.

Long-standing, insulin-treated type 2 diabetes patients with complications respond well to short-term resistance and interval exercise training.

OBJECTIVE: To determine the feasibility and the benefits of combined resistance and interval exercise training on phenotype characteristics and skeletal muscle function in deconditioned, type 2 diabetes (T2D) patients with polyneuropathy. DESIGN: Short-term, single-arm intervention trial. METHODS: Eleven male T2D patients (age: 59.1+/-7.5 years; body mass index: 32.2+/-4.0 kg/m2) performed progressive resistance and interval exercise training thrice a week for 10 weeks. Besides primary diabetes outcome measures, muscle strength (MUST), maximal workload capacity (Wmax), whole-body peak oxygen uptake (VO2peak) and muscle oxidative capacity (MUOX), intramyocellular lipid (IMCL) and glycogen (IMCG) storage, and systemic inflammation markers were determined before and after training. Daily exogenous insulin requirements (EIR) and historic individualized EIR were gathered and analysed. RESULTS: MUST and Wmax increased with 17% (90% confidence intervals 9-24%) and 14% (6-21) respectively. Furthermore, mean arterial blood pressure declined with 5.5 mmHg (-9.7 to -1.4). EIR dropped with 5.0 IU/d (-11.5 to 1.5) compared with baseline. A decline of respectively -0.7 mmol/l (-2.9 to 1.5) and -147 micromol/l (-296 to 2) in fasting plasma glucose and non-esterified fatty acids concentrations were observed following the intervention, but these were not accompanied by changes in VO2peak, MUOX, IMCL or IMCG, and blood glycolysated haemoglobin, adiponectin, tumor necrosis factor-alpha and/or cholesterol concentrations. CONCLUSION: Short-term resistance and interval exercise training is feasible in deconditioned T2D patients with polyneuropathy and accompanied by moderate improvements in muscle function and blood pressure. Such a specific exercise regimen may provide a better framework for future exercise intervention programmes in the treatment of deconditioned T2D patients.

Corticotroph axis sensitivity after exercise: comparison between elite athletes and sedentary subjects.

Strenuous exercise activates the hypothalamic-pituitary-adrenal (HPA) axis. Several reports showed that physical training is associated with a decreased efficiency of the feedback control of HPA axis. The aims of the present study were: 1) to evaluate the differences in the mechanical, hormonal, and lactate responses to a high-intensity isokinetic exercise among different groups of competitive athletes (CA, no.=20) of power and endurance disciplines and sedentary controls (SED, no.=10); 2) to determine the effects of the training status on the HPA axis responsiveness following exercise, as indirectly evaluated by the rates of ACTH, cortisol, and DHEA recovery after exercise. CA and SED fulfilled eight sets of twenty concentric contractions of the knee extensors at 180 degrees/sec angular velocity throughout a constant range of motion (100 degrees). There was a rest period of 30 sec between each set and a 3-min rest period between the two legs. Before, immediately after the isokinetic exercise and at different times in the subsequent 120 min of recovery, blood and saliva were sampled to determine plasma ACTH, salivary cortisol, serum DHEA, and serum lactate concentrations. CA showed a higher cortisol response to exercise than SED, whereas no differences were found in the responses of ACTH, DHEA and lactate. In the athlete group the exercise-induced increases of ACTH, cortisol, and lactate were higher in power athletes with respect to endurance athletes. No differences were observed between athletes and SED in the rates of hormonal recovery after exercise: this finding does not support the concept that a reduced feedback control of HPA axis can represent a feature of trained individuals.

31P MR spectroscopy and in vitro markers of oxidative capacity in type 2 diabetes patients.

BACKGROUND: Skeletal muscle mitochondrial function in type 2 diabetes (T2D) is currently being studied intensively. In vivo (31)P magnetic resonance spectroscopy ((31)P MRS) is a noninvasive tool used to measure mitochondrial respiratory function (MIFU) in skeletal muscle tissue. However, microvascular co-morbidity in long-standing T2D can interfere with the (31)P MRS methodology. AIM: To compare (31)P MRS-derived parameters describing in vivo MIFU with an in vitro assessment of muscle respiratory capacity and muscle fiber-type composition in T2D patients. METHODS: (31)P MRS was applied in long-standing, insulin-treated T2D patients. (31)P MRS markers of MIFU were measured in the M. vastus lateralis. Muscle biopsy samples were collected from the same muscle and analyzed for succinate dehydrogenase activity (SDH) and fiber-type distribution. RESULTS: Several (31)P MRS parameters of MIFU showed moderate to good correlations with the percentage of type I fibers and type I fiber-specific SDH activity (Pearson's R between 0.70 and 0.75). In vivo and in vitro parameters of local mitochondrial respiration also correlated well with whole-body fitness levels (VO (2peak)) in these patients (Pearson's R between 0.62 and 0.90). CONCLUSION: Good correlations exist between in vivo and in vitro measurements of MIFU in long-standing insulin-treated T2D subjects, which are qualitatively and quantitatively consistent with previous results measured in healthy subjects. This justifies the use of (31)P MRS to measure MIFU in relation to T2D.

Is minimally invasive surgery less invasive in total hip replacement? A pilot study.

It has been suggested that minimally invasive surgery (MIS) in total hip replacement (THR) is less traumatic than standard techniques. This study was designed to address the question of whether an anterior MIS approach generates less inflammation and muscle damage than the standard posterolateral (PL) approach. Inflammation parameters such as interleukin-6 (IL-6), muscle damage parameters like heart type fatty acid binding protein (H-FABP), and haemoglobin (Hb) levels were determined pre-operatively and at five consecutive points post-operatively in 10 patients operated through a MIS anterior approach and in 10 patients operated through a PL approach. The mean IL-6 concentration increased from 3 pg/ml in both groups pre-operatively to 78.5 pg/ml (PL group) vs 74.8 pg/ml (MIS group) at 6 hours post-operatively and reached a maximum of 100 pg/ml (PL group) vs 90.5 pg/ml pg/ml (MIS group) after 24 hours. Up to this time point, there was a decrease in both groups. The post-operative mean H-FABP concentration increased to 10.7 microg/l in the PL group vs 15.8 microg/l in the MIS group. It formed a plateau and decreased after 24 hours post-operatively. The Hb levels were 14.5 g/dl before surgery and decreased to 10.7 g/dl (PL group) and 10.0 g/dl (MIS group) at 72 hours post-operatively. No significant differences were found between the two approaches either in inflammation and muscle damage or blood loss. Although the absence of a learning curve may explain the lack of a difference between both techniques, we speculate that the term MIS is at least doubtful in terms of being less traumatic.

Experience in the first four years of rapid recovery; is it safe?

The average length of hospital stay after Total Hip Replacement (THR) has been decreasing over time. Recently, many hospitals have commenced rapid recovery programs such as Joint Care. In Joint Care the patients are usually discharged on the fifth post-operative day with relatively fresh surgical wounds. The aim of this study is to evaluate the Joint Care program after THR. Between February 2000 and February 2004, the Joint Care program was used in 611 patients after THR. The average age of the patients was 66.3 yrs (SD 9.3; range 24-86 yrs) and 68% (n= 415) of them were female. All clinical and outpatient charts as well as nursery records were evaluated. The follow up was from 6 months to 4 years (average: 2.5 years). At the planned fifth post-operative day, 92% (n = 562) of patients were discharged from hospital (SD 1.7 days; range 6-25 days). 3.8% (n= 23) of the remaining cases faced wound problems--prolonged wound drainage in 2.3% (n = 14) and potential superficial infection in 1.5% (n = 9) - causing a delay in their discharge. The readmission rate was 6.4% (n = 39) due to hip dislocation (3.4%; n = 21), re-evaluation of wound (1.5%; n= 9), deep infection (1.2%; n = 7)) and cardiac events (0.3%; n = 2). All the infection cases were treated effectively with debridement and antibiotics and no revision for any reason was reported. The Joint Care program seems to be effective after THR. Post-operative hip dislocation was the main reason for post-operative readmission. However, no clear signs that the intensive rehabilitation program caused more complications compared to previous regimens were evident. The above results encourage the application of rapid recovery programs in Orthopaedic surgery and joint replacement.

Is peri-operative cortisol secretion related to post-operative cognitive dysfunction?

BACKGROUND: The pattern of cortisol secretion is influenced by surgery. As cortisol can adversely affect neuronal function, this may be an important factor in the development of post-operative cognitive dysfunction (POCD). We hypothesized that the incidence of POCD would be related to changes in cortisol level. METHODS: We studied 187 patients aged over 60 years undergoing major non-cardiac surgery with general or regional anaesthesia. Saliva cortisol levels were measured pre-operatively and at 1 day, 7 days and 3 months post-operatively in the morning (08.00 h) and in the afternoon (16.00 h) using salivettes. Cognitive function was assessed pre-operatively, on day 7 and at 3 months using four neuropsychological tests. POCD was defined as a combined Z score of greater than 1.96. RESULTS: After surgery, salivary cortisol concentrations increased significantly. POCD was detected in 18.8% of subjects at 1 week and in 15.2% after 3 months. The pre-operative ratios between the morning and afternoon cortisol concentrations (am/pm ratios) were 2.8 and 2.7 in patients with POCD at 1 week vs. those without POCD at 1 week, respectively. The am/pm ratios decreased significantly post-operatively to 1.9 and 1.6 at 1 week, respectively (P = 0.02 for both). In an analysis considering all am/pm ratios, it was found that the persistent flattening in am/pm ratio was significantly related to POCD at 1 week. CONCLUSION: The pattern of diurnal variation in cortisol level was significantly related to POCD. Thus, circadian rhythm disturbance or metabolic endocrine stress could be an important mechanism in the development of cognitive dysfunction after major surgery.

Physical activity pattern of children assessed by triaxial accelerometry.

OBJECTIVES: Accelerometry was used to assess the relationship between the physical activity level (PAL) and time spent on activities of various intensities in children. DESIGN: A total of 20 children aged 8.6+/-3.3 y wore a triaxial accelerometer (Tracmor2) for 2 weeks. PAL was calculated with Tracmor2 output data. The fraction of time spent on activities with a given level of intensity (low, moderate, high) was calculated. The fractions of time spent on activities of different intensities were compared with previously obtained data for young adults and elderly persons. RESULTS: PAL showed an inverse relation with the percentage of time spent on low-intensity activities (r = -0.76; P < 0.0001) and a positive relation with the percentage of time spent on high-intensity activities (r = 0.93; P < 0.0001). The fraction of time spent on low-intensity activities was smaller in children than in young adults (P < 0.05) and elderly persons (P < 0.0001), while the fraction spent on high-intensity activities (P < 0.0001) was larger. CONCLUSIONS: The present data are important for a better understanding of physical activity in children, which is necessary for education and prevention about physical (in)activity in childhood. Our observations suggest that to obtain a higher PAL in children, they should be given the opportunities to perform high-intensity activities.

Cognitive dysfunction after minor surgery in the elderly.

BACKGROUND: Major surgery is frequently associated with postoperative cognitive dysfunction (POCD) in elderly patients. Type of surgery and hospitalization may be important prognostic factors. The aims of the study were to find the incidence and risk factors for POCD in elderly patients undergoing minor surgery. METHODS: We enrolled 372 patients aged greater than 60 years scheduled for minor surgery under general anesthesia. According to local practice, patients were allocated to either in- (199) or out-patient (173) care. Cognitive function was assessed using neuropsychological testing preoperatively and 7 days and 3 months postoperatively. Postoperative cognitive dysfunction was defined using Z-score analysis. RESULTS: At 7 days, the incidence (confidence interval) of POCD in patients undergoing minor surgery was 6.8% (4.3-10.1). At 3 months the incidence of POCD was 6.6% (4.1-10.0). Logistic regression analysis identified the following significant risk factors: age greater than 70 years (odds ratio [OR]: 3.8 [1.7-8.7], P = 0.01) and in- vs. out-patient surgery (OR: 2.8 [1.2-6.3], P = 0.04). CONCLUSIONS: Our finding of less cognitive dysfunction in the first postoperative week in elderly patients undergoing minor surgery on an out-patient basis supports a strategy of avoiding hospitalization of older patients when possible.

Effect of testosterone and endurance training on glycogen metabolism in skeletal muscle of chronic hyperglycaemic female rats.

OBJECTIVES: To investigate in glycolytic and oxidative muscles of trained (nine weeks) and untrained hyperglycaemic female rats the effect of hyperandrogenicity and/or endurance training on energy metabolic properties. METHODS: Glycogen content and activity of muscle enzymes with regulatory functions in glycogen synthesis were examined. RESULTS: Testosterone treatment increased glycogen content of extensor digitorum longus (EDL) and soleus muscles of hyperglycaemic sedentary (18% and 84% respectively) and hyperglycaemic trained (7% and 16% respectively) rats. In both types of muscle of the hyperglycaemic testosterone treated exercised subgroup, less depletion of glycogen was found than in the untreated group (38% and 87% for EDL and soleus respectively). CONCLUSIONS: The mechanisms by which training and/or hyperandrogenism alone or in combination elicits their specific effects are complex. Differences in sex, surgery, levels of hormones administered, and exercise model used may be the main reasons for the observed discrepancies. Conclusions from the results: (a) hyperandrogenism is not a primary cause of the development of insulin resistance; (b) glycogen content of slow and fast twitch muscle is increased by training through increased glycogen synthase activity. The most plausible explanation for differences between different muscle fibre types is the different levels of expression of androgen receptors in these fibres. Hyperandrogenicity therefore acts on energy metabolic variables of hyperglycaemic animals by different mechanisms in glycolytic and oxidative muscle fibres.

Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction: a case study.

The data of the present case demonstrate that the abuse of androgenic anabolic steroids (AAS) may lead to serious health effects. Although most clinical attention is usually directed towards peripheral side effects, the most serious central side effect, hypothalamic-pituitary-dysfunction, is often overlooked in severe cases. Although this latter central side-effect usually recovers spontaneously when AAS intake is discontinued, the present case shows that spontaneous recovery does not always take place. We suggest that hypothalamic-pituitary dysfunction should always be considered in the differential diagnosis in athletes seen with typical presentation of anabolic steroid use. In order to regain normal hypothalamic-pituitary function, supraphysiological doses of 200 microg LH-RH should be considered when the physiological challenge test with LH-RH (50 microg) fails to show an acceptable response.

Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac and major non-cardiac surgery with general anaesthesia in the elderly. We hypothesized that the incidence of POCD would be less with regional anaesthesia rather than general. METHODS: We included patients aged over 60 years undergoing major non-cardiac surgery. After giving written informed consent, patients were randomly allocated to general or regional anaesthesia. Cognitive function was assessed using four neuropsychological tests undertaken preoperatively and at 7 days and 3 months postoperatively. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in two or more test parameters. RESULTS: At 7 days, POCD was found in 37/188 patients (19.7%, [14.3-26.1%]) after general anaesthesia and in 22/176 (12.5%, [8.0-18.3%]) after regional anaesthesia, P = 0.06. After 3 months, POCD was present in 25/175 patients (14.3%, [9.5-20.4%]) after general anaesthesia vs. 23/165 (13.9%, [9.0-20.2%]) after regional anaesthesia, P = 0.93. The incidence of POCD after 1 week was significantly greater after general anaesthesia when we excluded patients who did not receive the allocated anaesthetic: 33/156 (21.2%[15.0-28.4%]) vs. 20/158 (12.7%[7.9-18.9%]) (P = 0.04). Mortality was significantly greater after general anaesthesia (4/217 vs. 0/211 (P < 0.05)). CONCLUSION: No significant difference was found in the incidence of cognitive dysfunction 3 months after either general or regional anaesthesia in elderly patients. Thus, there seems to be no causative relationship between general anaesthesia and long-term POCD. Regional anaesthesia may decrease mortality and the incidence of POCD early after surgery.

Misuse of androgenic-anabolic steroids and human deltoid muscle fibers: differences between polydrug regimens and single drug administration.

The objective of this investigation was to study the effects of androgenic-anabolic steroid (AAS) misuse on deltoid muscle fiber characteristics in experienced, male strength-trained athletes. In a double-blind study, 15 volunteers were administered nandrolone decanoate (ND) for 8 weeks (200 mg/week, intramuscularly). In an additional study, 12 subjects self-administered various AASs at supratherapeutic dosages (AAS group), while 7 non-users served as controls. In all subjects, a percutaneous needle biopsy sample of the deltoid muscle was obtained at baseline and after 8 weeks. Muscle sections were pre-incubated at pH 4.4, stained with adenosine triphosphatase and analyzed morphometrically. In each biopsy sample, at least 150 fibers were classified for "gray level" and "lesser fiber diameter" to determine the mean fiber size, the sizes of type I and type II fibers, and the fiber type distribution. ND administration did not seem to affect any of those parameters. In the AAS group, mean muscle fiber size (+ 12.6%), and the size of type I (+ 10.8%) and type II (+ 14.6%) muscle fibers increased. The fiber type distribution remained unaltered. We conclude that polydrug regimens of AAS misuse at supratherapeutic dosages increased the size of deltoid muscle fibers (especially type II fibers) in experienced strength-trained athletes, while ND at a therapeutic intramuscular dose of 200 mg did not exert any effect.

Acute and sustained effects of isometric and lengthening muscle contractions on high-energy phosphates and glycogen metabolism in rat tibialis anterior muscle.

Previous studies have shown that lengthening contractions, in contrast to isometric contractions, readily result in sustained malfunctioning of the exercised muscles. The present study was performed to investigate whether an exercise period with many (240) lengthening contractions (LC) results in alterations in muscle high-energy phosphates and inosine monophosphate (IMP) content, different from muscles performing a few (60) lengthening or a few (60) or many (240) isometric contractions (IC). Moreover, we sought for a possible cause(s) of the inability to replenish muscle glycogen stores following LC. Rat tibialis anterior muscles were subjected in vivo to either 60 or 240 LC or IC. Structural muscle damage occurred only after 240 LC. The fact that tissue glycogen levels declined to a similar extent during LC and IC suggests that the energy demand was comparable during both types of exercise. Nevertheless, the observation that on the one hand tissue stores of adenine nucleotides showed a greater decline, and on the other hand the tissue content of IMP increased to a significantly higher level after LC than after IC, clearly indicates that muscle energy metabolism is more disturbed during LC than during IC. The high tissue levels of IMP may contribute to impaired mechanical function as previously observed in muscles subjected to LC. In contrast to 240 IC, 24 hours after 240 LC, tissue glycogen stores and high-energy phosphate levels were not restored to control values. The present findings indicate that depressed glycogen synthase activity and impaired activity of the mitochondrial marker enzyme cytochrome C oxidase probably contribute to a continuous disturbance of energy metabolism in the exercised muscles during the 24 hours following 240 LC.

Skeletal muscle metabolic characteristics before and after energy restriction in human obesity: fibre type, enzymatic beta-oxidative capacity and fatty acid-binding protein content.

BACKGROUND: Skeletal muscle has the ability to adapt as result of dietary, hormonal or pharmacological interventions affecting energy metabolism. The aim of the present study was to investigate the effects of energy restriction on skeletal muscle metabolic characteristics in obese women. METHODS: The effects of 8 weeks' energy restriction on body composition, energy expenditure and skeletal muscle characteristics were investigated in 28 healthy obese women. Subjects were aged 37.9 +/- 1.5 years and had a body mass index of 32.0 +/- 0.8 kg m-2. RESULTS: Energy restriction (2800 kJ day-1) resulted in a 10.8 +/- 0.5 kg weight loss consisting of 8. 6 +/- 0.5 kg of fat mass and 2.2 +/- 0.3 kg of fat-free mass. Basal respiratory exchange ratio, sleeping metabolic rate and exercise-induced thermogenesis significantly declined in response to the diet. These changes were accompanied by an increase (P = 0.038) in the skeletal muscle content of cytosolic fatty acid-binding protein (H-FABP), whereas no changes occurred in fibre type distribution or activities of enzymes reflecting beta-oxidation and mitochondrial density (3-hydroxyacyl-CoA dehydrogenase and citrate synthase respectively). CONCLUSION: The results suggest that increased capacity of intracellular fatty acid transport in skeletal muscle cells is involved in the physiological adaptations of fat metabolism to energy restriction in obese female subjects.

Body composition, cardiovascular risk factors and liver function in long-term androgenic-anabolic steroids using bodybuilders three months after drug withdrawal.

The purpose of this study was to investigate in a cross-sectional design body composition, muscle fiber characteristics, cardiovascular risk factors and liver enzymes in long-term androgenic-anabolic steroids (AAS) using bodybuilders three months after drug withdrawal (AAS group; n = 16) and in non-users (CO group; n = 12). Training and dietary data were collected in all subjects. Anthropometry included weight, height, 8 skinfolds and 11 circumferences. Percentage fat (%FAT), fat mass (FM) and lean body mass (LBM) were calculated. In a muscle biopsy from the vastus lateralis muscle water content, fiber type distribution and diameters of fiber type I and type II were determined. Age, height, training characteristics, nutrition, skinfolds, %FAT and FM did not differ between the groups. The AAS group had greater BW and LBM, and larger circumferences of thorax, waist, upper arm and thigh than the CO group. Muscle biopsy data were comparable, except for muscle fiber diameter of type I which was larger in the AAS group. No differences in serum values of total cholesterol, HDL-cholesterol and triglycerides, nor in systolic and diastolic blood pressure were observed. In both groups serum alkaline phosphatase and gamma GT were within the normal range. This study suggests that in long term AAS using body-builders, after a three months AAS free period, BW is greater than in non drug users. This is reflected in larger LBM, circumferences and diameter of muscle fiber type I. In addition, no differences in fat mass, blood pressure, lipoprotein profiles and liver enzymes exist between AAS users three months after interrupted drug use and their non drug using counterparts.