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OBJECTIVE: To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching (NFOR). DESIGN: A prospective case-control study using a monthly performance monitor with a standardised field test to detect the performance changes. Players with a performance decrease lasting at least 1 month were compared with control players without a performance decrease on mood scores and pre-exercise and postexercise levels of stress hormones. SETTING: Sporting field and sports medical laboratory. PARTICIPANTS: Ninety-four young elite soccer players were monitored during the 2006-2008 seasons. Twenty-one players were invited to the laboratory, seven of whom showed a significant performance decrease. MAIN OUTCOME MEASURES: Performance change over time, scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone (ACTH), growth hormone (GH) and cortisol. RESULTS: Players with a performance decrease showed psychological and hormonal changes typical of the non-functional state of over-reaching. Scores were higher on depression and anger, whereas the resting GH levels and ACTH levels after maximal exercise were reduced. ACTH and GH were capable of classifying all but one player correctly as either NFOR or control. CONCLUSIONS: Performance-related criteria in field tests are capable of identifying players with worsened mood and adaptations of the endocrine system that fit the definition of NFOR. Performance, mood and hormone levels may therefore be considered as valid instruments to diagnose NFOR in young elite soccer players. [ABSTRACT FROM AUTHOR]

Objective To study whether field performance tests can make a valid distinction between non-functionally overreaching (NFO) athletes and control athletes. Design Monthly field performance tests were used to determine a performance decrement (PD) throughout a season. Athletes with a minimum of 1 month PD were compared with control athletes without a PD on mood characteristics and resting levels of stress hormones. Setting Sporting field and sports medical laboratory. Participants 129 young elite athletes, 77 soccer players and 52 middle-long distance runners were followed prospectively during the 2006-2007 season. Fifteen of them were invited to the laboratory. Eight athletes showed a performance decrease lasting longer than 1 month, and seven athletes without a performance decrease acted as their controls. Main outcome measures Performance changes over time were measured using field tests. Profile of Mood States and resting levels of adrenocorticotrophic hormone (ACTH) and cortisol in blood were measured in the laboratory. Results PD athletes showed several symptoms typical of the non-functional state of overreaching (OR). The PD group scored higher on depression and anger than controls. They also showed a specific pattern of correlations between negative mood subscales (tension, fatigue and depression), which was absent in controls. ACTH levels at rest were similar, but lower cortisol levels in PD athletes pointed at a blunted cortisol response. Cortisol levels were decoupled from ACTH levels only in PD athletes. Conclusions Implementing performance-related criteria in field tests can help coaches and sports physicians to distinguish NFO athletes from athletes with balanced workload and recovery. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review describes the state of the art of the impact of hypothyroidism on exercise tolerance and physical performance capacity in untreated and treated patients with hypothyroidism., Method: A systematic computer-aided search was conducted using biomedical databases. Relevant studies in English, German, and Dutch, published from the earliest date of each database up to December 2012, were identified., Results: Out of 116 studies, a total of 38 studies with 1,379 patients fulfilled the inclusion criteria. These studies emphasize the multifactorial causes of exercise intolerance in untreated patients by the impact of limitations in different functional systems, with cardiovascular, cardiopulmonary, musculoskeletal, neuromuscular, and cellular metabolic systems acting in concert. Moreover, the studies affirm that exercise intolerance in patients is not always reversible during adequate hormone replacement therapy. As a consequence, despite a defined euthyroid status, there remains a significant group of treated patients with persistent complaints related to exercise intolerance who are suffering from limitations in daily and sport activities, as well as an impaired quality of life. An explanation for this phenomenon is lacking. Only 2 studies investigated the effects of a physical training program, and they showed inconsistent effects on the performance capacity in untreated patients with subclinical hypothyroidism., Conclusions: A limited body of knowledge exists concerning exercise tolerance in treated patients with hypothyroidism, and there is an insufficient amount of quantitative studies on the effects of a physical training program. To enhance exercise and sports participation for this specific group, more research in this forgotten area is warranted.

To identify target groups for injury prevention in male amateur soccer players under 35 years of age. A computer-assisted telephone survey with a 12-month recall period for injuries in a representative sample of Dutch citizens from the Injuries and Physical Activity Netherlands (IPAN)-database. A comparison of the volume of soccer injuries, the incidence and the need for medical attention per level of exposure and age category. The incidence in seniors was twice that of juniors (17.5% versus 8.1%; odds ratio (OR=2.4). In juniors the overall incidence was lowest in the category with the least amount of soccer exposure time (0-3 h: 2.9%; 3-5 h: 13.0%; 5+ h: 12.3%). A comparable result was found in seniors: (0-3 h: 12.0%; 3-5 h: 21.6%; 5+ h: 21.5%). Within each level of soccer exposure, a different incidence was found in juniors and seniors (0-3 h: OR=4.6; 3-5 h: OR=1.8; 5+ h: OR=1.9). Ankle, knee and upper leg injuries were most common (59.9%). Contusions, strains and sprains dominated (78.1%). Body region and type of injuries were similar in both age categories. Medical treatment for injuries was equally necessary in both age groups. Senior male amateur soccer players and particularly the more skilled seniors (involved in soccer at least 3 h per week), should be primarily targeted for studies on injury risk factors and prevention programs., (Copyright © 2010 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Objective: To summarize the current evidence on the effects of preoperative exercise therapy in patients awaiting invasive surgery on postoperative complication rate and length of hospital stay., Data Sources: A primary search of relevant key terms was conducted in the electronic databases of PubMed, EMBASE, PEDro and CINAHL., Review Methods: Studies were included if they were controlled trials evaluating the effects of preoperative exercise therapy on postoperative complication rate and length of hospital stay. The methodological quality of included studies was independently assessed by two reviewers using the PEDro scale. Statistical pooling was performed when studies were comparable in terms of patient population and outcome measures. Results were separately described if pooling was not possible., Results: Twelve studies of patients undergoing joint replacement, cardiac or abdominal surgery were included. The PEDro scores ranged from 4 to 8 points. Preoperative exercise therapy consisting of inspiratory muscle training or exercise training prior to cardiac or abdominal surgery led to a shorter hospital stay and reduced postoperative complication rates. By contrast, length of hospital stay and complication rates of patients after joint replacement surgery were not significantly affected by preoperative exercise therapy consisting of strength and/or mobility training., Conclusion: Preoperative exercise therapy can be effective for reducing postoperative complication rates and length of hospital stay after cardiac or abdominal surgery. More research on the utility of preoperative exercise therapy and its long-term effects is needed as well as insight in the benefits of using risk models.

Background: The delay in O(2) uptake kinetics during and after submaximal physical activity (O(2) onset and recovery kinetics, respectively) correlates well with the functional capacity of patients with chronic heart failure (CHF). This study examined the physiological background of this delay in moderately impaired CHF patients by comparing kinetics of cardiac output (Q) and O(2) uptake (V(O(2)))., Methods: Fourteen stable CHF patients (New York Heart Association class II-III) and 8 healthy subjects, matched for age and body mass index, were included. All subjects performed a submaximal constant-load exercise test to assess O(2) uptake kinetics. Furthermore, in 10 CHF patients Q was measured by a radial artery pulse contour analysis method, which enabled the simultaneous modelling of exercise-related kinetics of Q and V(O(2))., Results: Both O(2) onset and recovery kinetics were delayed in the patient group. There were no significant differences between the time constants of Q and V(O(2)) during exercise-onset (62+/-25 s versus 59+/-28 s, p=0.51) or recovery (61+/-25 s versus 57+/-20 s, p=0.38) in the patient group, indicating that O(2) delivery was not in excess of the metabolic demands in these patients., Conclusion: The delay in O(2) onset and recovery kinetics in moderately impaired CHF patients is suggested to be due to limitations in O(2) delivery. Therefore, strategies aimed at improving exercise performance of these patients should focus more on improvements of O(2) delivery than on O(2) utilization., (Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.)

Traditionally, the effects of physical training in patients with chronic heart failure (CHF) are evaluated by changes in peak oxygen uptake (peak VO(2)). The assessment of peak VO(2), however, is highly dependent on the patients' motivation. The aim of the present study was to evaluate the clinical utility of effort-independent exercise variables for detecting training effects in CHF patients. In a prospective controlled trial, patients with stable CHF were allocated to an intervention group (N = 30), performing a 12-week combined cycle interval and muscle resistance training program, or a control group (N = 18) that was matched for age, gender, body composition and left ventricular ejection fraction. The following effort-independent exercise variables were evaluated: the ventilatory anaerobic threshold (VAT), oxygen uptake efficiency slope (OUES), the V(E)/VCO(2) slope and the time constant of VO(2) kinetics during recovery from submaximal constant-load exercise (tau-rec). In addition to post-training increases in peak VO(2) and peak V(E), the intervention group showed significant within and between-group improvements in VAT, OUES and tau-rec. There were no significant differences between relative improvements of the effort-independent exercise variables in the intervention group. In contrast with VAT, which could not be determined in 9% of the patients, OUES and tau-rec were determined successfully in all patients. Therefore, we conclude that OUES and tau-rec are useful in clinical practice for the assessment of training effects in CHF patients, especially in cases of poor subject effort during symptom-limited exercise testing or when patients are unable to reach a maximal exercise level.

CHF (chronic heart failure) is associated with a prolonged recovery of skeletal muscle energy stores following submaximal exercise, limiting the ability to perform repetitive daily activities.However, the pathophysiological background of this impairment is not well established. The aim of the present study was to investigate whether muscle metabolic recovery following submaximal exercise in patients with CHF is limited by O2 delivery or O2 utilization. A total of 13 stable CHF patients (New York Heart Association classes II-III) and eight healthy subjects, matched for age and BMI (body mass index), were included. All subjects performed repetitive submaximal dynamic single leg extensions in the supine position. Post-exercise PCr (phosphocreatine) resynthesis was assessed by 31P-MRS (magnetic resonance spectroscopy). NIRS (near-IR spectroscopy) was applied simultaneously, using the rate of decrease in HHb (deoxygenated haemoglobin) as an index of post-exercise muscle re-oxygenation. As expected, PCr recovery was slower in CHF patients than in control subjects (time constant, 47+/-10 compared with 35+/-12 s respectively; P=0.04). HHb recovery kinetics were also prolonged in CHF patients (mean response time, 74+/-41 compared with 44+/-17 s respectively; P=0.04). In the patient group, HHb recovery kinetics were slower than PCr recovery kinetics (P=0.02), whereas no difference existed in the control group(P=0.32). In conclusion, prolonged metabolic recovery in CHF patients is associated with an even slower muscle tissue re-oxygenation, indicating a lower O(2) delivery relative to metabolic demands. Therefore we postulate that the impaired ability to perform repetitive daily activities in these patients depends more on a reduced muscle blood flow than on limitations in O(2) utilization.

Objective: Conventional surgical treatment for small saphenous vein (SSV) reflux is associated with high recurrence rates and complications. Endovenous laser ablation (EVLA) is a treatment modality with promising results. This study reports patient satisfaction and short-term results after EVLA of SSV reflux., Methods: Fifty-two legs of 49 consecutive patients were treated with EVLA for reflux of the SSV. Patients were investigated clinically and by duplex scanning before and 6 weeks after treatment. Patient records were studied and a questionnaire was completed., Results: Technical success was accomplished in all patients. After 6 weeks the occlusion rate was 100% and after 6.5 months no recurrent varicosities were reported. Complications consisted of bruising (51%), induration (39%), delayed tightness (16%), phlebitis (2%), and temporary paresthesia (6%) and were all self-limiting. One deep venous thrombosis occurred in a patient with a protein C deficiency. Ninety-two percent (45/49) of patients were satisfied with the results and in 98% symptoms had significantly improved or completely disappeared. Working activities were resumed after a mean of 4 days. Forty-three patients (88%) would consider having endovenous laser treatment again if indicated., Conclusions: EVLA of the SSV seems to be a safe modality with excellent short-term results and high patient satisfaction. Controlled studies assessing the effectiveness of EVLA in comparison to conventional treatment of SSV reflux are crucial before considering EVLA as the standard treatment.

One of the hallmark symptoms of patients with chronic heart failure (CHF) is exercise intolerance. Therefore, exercise testing has become an important tool for the evaluation and monitoring of heart failure. Whereas the maximal aerobic capacity (peak VO(2)) is a reliable indicator of the severity and prognosis of heart failure, submaximal exercise parameters may be more closely related to the ability to perform daily activities. As such, oxygen (O(2)) uptake kinetics, describing the rate change of O(2) uptake during onset or recovery of submaximal constant-load exercise (O(2) onset and recovery kinetics, respectively), have been shown to be useful parameters for objectively evaluating the functional capacity of CHF patients. However, their evaluation in this population is not a routine part of daily clinical practice. Possible reasons for this include a lack of standardisation of the assessment methodology and a limited number of studies evaluating the clinical use of O(2) uptake kinetics in CHF patients. In addition, the pathophysiological mechanisms underlying the delay in O(2) uptake kinetics in these patients are not completely understood. This review discusses the current literature on the clinical potency and physiological determinants of O(2) uptake kinetics in CHF patients and provides directions for future research. (Neth Heart J 2009;17:238-44.Neth Heart J 2009;17:238-44.).

Background: A persistent sciatic artery (PSA) is a rare vascular anomaly with an estimated incidence of 0.03-0.06%. During early embryonic development, the sciatic artery usually disappears when the superficial femoral artery has developed properly. This study aimed to assess the clinical presentation and outcome of a PSA., Method: A systematic review of all cases of PSA published between 1964 and 2007 was performed., Results: In this review, 159 PSAs were described in 122 patients. The mean age at which the PSA was discovered was 57 years, and the incidence was equally distributed with regards to gender. The majority of PSAs was unilateral (70%) and of the complete type (79%). Ninety-one patients (80%) presented with symptoms including intermittent claudication, ischaemia, a pulsating mass or neurological symptoms. An aneurysm was found in 48%, a stenosis in 7%, an occlusion of the PSA in 9% and an occlusion of an artery distal to the PSA in 6% of the subjects. The treatment depended on the symptoms and classification of the PSA. In nine cases (8%), an amputation was required eventually., Conclusion: The PSA is a rare anomaly with a high incidence of complications including aneurysm formation and ischaemia that may lead to amputation. Strategies for follow-up could not be deduced from the available literature.

Background: Since available studies have provided conflicting results, this study investigated respiratory muscle function and its relationship with exercise capacity, degree of dyspnoea and leg discomfort, and quality of life in patients with Cystic Fibrosis (CF)., Methods: Using a cross-sectional design, 27 clinically stable adolescent and adult patients (f/m: 14/13, age: 26+/-7 years) were included. Data of respiratory muscle strength (P(i)max and P(e)max), lung function (spirometry), peripheral muscle strength (peak isometric quadriceps and hand-grip strength), symptom-limited exercise capacity (modified shuttle test, MST), post-exercise dyspnoea and leg discomfort (Borg scores), and quality of life (CFQ-14+, MRC) were obtained for further analysis., Results: P(i)max of the total patient group was significantly higher than reference values (P(i)max=124+/-32% predicted), and correlated positively with the walk/run distance of the MST (r(s)=0.59, p=0.00). Female patients showed more dyspnoea and a more impaired lung function than male patients. However, P(i)max and P(e)max (% predicted) showed a tendency to be higher in female than in male patients., Conclusion: Increased work of breathing will have a conditioning effect on the respiratory muscles, suggesting that training-related inspiratory muscle strength can play a positive role in the limited exercise capacity of CF patients.

Herein, we report a single institution's experience with endovascular abdominal aortic aneurysm repair in nonagenarians, over a 4-year period of time. We performed a retrospective study of cases, in which we documented patient demographics, symptoms, physical findings, surgical interventions, complications, and deaths. The survivors answered a questionnaire. Endovascular abdominal aneurysm repair was performed in 4 male nonagenarians (age range, 90-92 yr): 2 underwent repair of asymptomatic aneurysm and 2 underwent repair of symptomatic aneurysm. There was no in-hospital death, and patients were discharged after a median time of 11 days. Both patients with symptomatic abdominal aortic aneurysm died within 30 days, 1 of an occluded left femoral artery and the other of unknown cause. After follow-ups of 6 and 54 months, both survivors were in good physical condition and patient satisfaction appeared to be very high. We have shown that elective endovascular abdominal aneurysm repair in a small, selected group of nonagenarians was feasible and afforded acceptable short-term survival. In patients with symptomatic disease, however, the early postprocedural mortality rate appears to be high. Decision-making should focus chiefly on comorbidities, on subjective issues such as fear of rupture, and on ethical and financial considerations.

The purpose of this study was to evaluate the accuracy of two techniques for the continuous assessment of cardiac output in patients with chronic heart failure (CHF): a radial artery pulse contour analysis method that uses an indicator dilution method for calibration (LiDCO) and an impedance cardiography technique (Physioflow), using the Fick method as a reference. Ten male CHF patients (New York Heart Association class II-III) were included. At rest, cardiac output values obtained by LiDCO and Physioflow were compared with those of the direct Fick method. During exercise, the continuous Fick method was used as a reference. Exercise, performed on a cycle ergometer in upright position, consisted of two constant-load tests at 30% and 80% of the ventilatory threshold and a symptom-limited maximal test. Both at rest and during exercise LiDCO showed good agreement with reference values [bias +/- limits of agreement (LOA), -1% +/- 28% and 2% +/- 28%, respectively]. In contrast, Physioflow overestimated reference values both at rest and during exercise (bias +/- LOA, 48% +/- 60% and 48% +/- 52%, respectively). Exercise-related within-patient changes of cardiac output, expressed as a percent change, showed for both techniques clinically acceptable agreement with reference values (bias +/- LOA: 2% +/- 26% for LiDCO, and -2% +/- 36% for Physioflow, respectively). In conclusion, although the limits of agreement with the Fick method are pretty broad, LiDCO provides accurate measurements of cardiac output during rest and exercise in CHF patients. Although Physioflow overestimates cardiac output, this method may still be useful to estimate relative changes during exercise.

The purpose of this study was to investigate which patient characteristics may predict training effects on maximal and submaximal exercise performance in patients with heart failure. Together with commonly used clinical and performance-related variables, oxygen uptake kinetics during exercise recovery were included as possible predictors. Fifty patients with heart failure (New York Heart Association class II or III) performed a 12-week training program (cycle interval and resistance training). Training effects were expressed as changes in peak oxygen uptake (Vo(2)), Vo(2) at ventilatory threshold (VT), and the time constant of Vo(2) recovery after submaximal exercise (tau-rec). After training, peak Vo(2), Vo(2) at VT, and tau-rec improved significantly, with a wide variety in training responses. Changes in peak Vo(2) were related to changes in VT (r = 0.79, p <0.001), but both changes were not related to changes in tau-rec. Using multivariate regression analyses, post-training changes in peak Vo(2) could be predicted by recovery halftime of peak Vo(2) (T1/2), peak Vo(2) (percentage of predicted), and peak respiratory exchange ratio (R(2) = 36%). Post-training changes in VT could be predicted by T1/2 and VT (predicted) (R(2) = 29%), whereas changes in tau-rec could be predicted only by tau-rec at baseline (R(2) = 34%). In conclusion, oxygen recovery kinetics after maximal and submaximal exercise substantially add to the prediction of training effects in patients with heart failure, presumably because of their relations with, respectively, central and peripheral impairments of exercise capacity. However, the explained variance in training effects is not sufficient to make a definite distinction between training responders and nonresponders.

Oxygen (O2) kinetics reflect the ability to adapt to or recover from exercise that is indicative of daily life. In patients with chronic heart failure (CHF), parameters of O2 kinetics have shown to be useful for clinical purposes like grading of functional impairment and assessment of prognosis. This study compared the goodness of fit and reproducibility of previously described methods to assess O2 kinetics in these patients. Nineteen CHF patients, New York Heart Association class II-III, performed two constant-load tests on a cycle ergometer at 50% of the maximum workload. Time constants of O2 onset- and recovery kinetics (tau) were calculated by mono-exponential modeling with four different sampling intervals (5 and 10 s, 5 and 8 breaths). The goodness of fit was expressed as the coefficient of determination (R2). Onset kinetics were also evaluated by the mean response time (MRT). Considering O2 onset kinetics, tau showed a significant inverse correlation with peak- VO2 (R = -0.88, using 10 s sampling intervals). The limits of agreement of both tau and MRT, however, were not clinically acceptable. O2 recovery kinetics yielded better reproducibility and goodness of fit. Using the most optimal sampling interval (5 breaths), a change of at least 13 s in tau is needed to exceed normal test-to-test variations. In conclusion, O2 recovery kinetics are more reproducible for clinical purposes than O2 onset kinetics in moderately impaired patients with CHF. It should be recognized that this observation cannot be assumed to be generalizable to more severely impaired CHF patients.

Objective: It is not well known whether physical activity (PA) is useful in the management of patients complaining of constipation. The aim of this study was to test the influence of regular PA on colonic transit time and defecation in middle-aged inactive patients suffering from chronic idiopathic constipation., Material and Methods: Forty-three subjects (> 45 years) were randomly divided into group A (n = 18, 16 F, 2 M) and group B (n = 25, 20 F, 5 M). Group A subjects maintained their normal lifestyle during 12 weeks, followed by a 12-week PA programme. Group B performed a 12-week PA programme after randomization. PA comprised 30 min of brisk walking and a daily 11-min home-based programme. Both groups received dietary advice. Colonic transit time was measured using a radiographic multiple marker single film technique., Results: Despite dietary advice, mean fibre and fluid intake did not change. In group B a significant reduction in 3 out of 4 of the Rome I criteria for constipation was observed, i.e. percentage of incomplete defecations, percentage of defecations requiring straining and percentage of hard stools (p < 0.05). As a consequence, the number of fulfilled Rome criteria for constipation decreased (2.7 to 1.7; p < 0.05). Furthermore, the rectosigmoid and total colonic transit time decreased (17.5 to 9.6 h and 79.2 to 58.4 h, respectively; p < 0.05). After PA the number of fulfilled Rome criteria also decreased in group A (2.6 to 1.7; p < 0.05)., Conclusions: In middle-aged inactive subjects with symptoms of chronic constipation, it is advisable to promote regular physical activity since it improves both the defecation pattern and rectosigmoid or total colonic transit time.

Objective and Design: Ageing and obesity result in decreased activity of the GH/IGF-I axis and concomitant impaired GH responses to secretory stimuli. We therefore determined the validity of the GH cut-off value of 15.0 microg/l in the GH-releasing hormone (GHRH)/GH releasing peptide-6 (GHRP-6) test for the diagnosis of GH deficiency in elderly or severely obese men., Methods: We performed a combined GHRH/GHRP-6 test in ten elderly men (mean age 74 years; mean body mass index (BMI) 24.6 kg/m(2)), nine obese men (mean age 47 years; mean BMI 40.6 kg/m(2)) and seven healthy male controls (mean age 51 years, mean BMI 24.3 kg/m(2)). After assessment of fasting plasma GH, IGF-I and IGF-binding protein-3 (IGFBP-3), GHRH (100 microg) and GHRP-6 (93 microg) were given intravenously as a bolus injection. Repeated GH measurements were performed for two hours., Results: Both peak GH levels and areas under the curve (AUC) were significantly lower in the obese than in the controls (peak 13.2 vs 53.4 microg/l, P = 0.001; AUC 707 vs 3250 microg/l x 120 min; P = 0.001). Mean GH response in the elderly was lower than in the controls (peak 35.0 microg/l; AUC 2274 microg/l x 120 min), but this was not statistically significant. In contrast, GH peak levels in seven obese men remained below the cut-off level of 15.0 microg/l associated with severe GH deficiency. All others had GH peak levels exceeding this threshold. IGFBP-3 levels were significantly lower in the elderly than in the controls (1.35 vs 2.05 mg/l, P = 0.001). Baseline GH or IGF-I did not differ significantly between groups., Conclusions: GH responses following GHRH/GHRP-6 administration were significantly reduced in severely obese men, but were not significantly reduced in elderly men, despite a negative trend. Our data indicate that the cut-off GH level of 15.0 microg/l after GHRH + GHRP-6 administration for the diagnosis of severe GH deficiency cannot be used in severely obese men.

This study was designed to investigate the central neuroendocrine mechanisms by which exercise (EX) stimulates growth hormone (GH) release as a function of age. Twelve male subjects, six in their early-to-mid twenties and six in their late sixties or seventies, received a strong GH stimulus either as incremental EX until volitional exhaustion or by administration of GHRH alone or Hex alone two hours after a presumed maximal GH response to combined administration of GHRH plus hexarelin (Hex). Total GH availability was calculated as area under the curve (AUC) over time periods 0 - 120 and 120 - 240 min. The mean AUC in micro g/l x 120 min to GHRH+Hex in the younger group was approximately twice that in the older group (11,260, range 3,947 - 19,007 vs. 5,366, range 2,262 - 8,654). In younger males, the mean AUC to EX (509, range 0 - 1,151) was larger than to GHRH (119, range 0 - 543), but less than that to Hex (919, range 0 - 1,892). In the older group, GH responses to EX and GHRH were abolished (mean AUC: 112, range 0 - 285, and 156, range 30 - 493), respectively) in contrast to the response to Hex (1,077, range 189 - 1,780). These data indicate that maximal GH stimulation by GHRH+Hex results in greater desensitization of GHRH compared to Hex, irrespective of age. We postulate that the abolished responsiveness of GH to EX in older group is due to insufficient disinhibition of hypothalamic somatostatin activity and desensitization of GHRH, while the preserved activity of a central Hex-related pathway is not involved. The GH response to EX in younger males is due to complete inhibition of somatostatin activity and stimulation of a central Hex-related pathway in spite of GHRH desensitization. We conclude that a central Hex-related pathway is the primary factor for EX-induced GH release only in younger males.

Cardiomyopathy is a major cause of death in overt acromegaly. Recent progress in research has increasingly revealed the molecular mechanisms concerning growth hormone and insulin-like growth factor in the development of heart failure. In this article, we propose mechanisms according to which heart failure occurs, and we aim to extrapolate this knowledge to more general processes involved in heart failure.

Background: Chronic heart failure (CHF) is characterized by symptoms like fatigue, dyspnoea and limited exercise performance. It has been postulated that maximal exercise performance (Wmax) is predominantly limited by skeletal muscle function and less by heart function., Aim: To study the interrelation between most relevant muscle and anthropometrical variables and Wmax in CHF patients in order to develop a model that describes the impact of these variables for maximal exercise performance., Design: In 77 patients with CHF Wmax was assessed by incremental cycle ergometry until exhaustion (20 Watt/3 min). Peak torque (strength) and total work (endurance) for the quadriceps and hamstrings were assessed by isokinetic dynamometry. Isometric strength was measured by hand dynamometry. Relevant muscle areas were calculated by computerized tomography scan., Results: Significant correlations between Wmax and isokinetic muscle parameters (peak torque and total work) ranged from 0.41-0.65 (P<0.01). Other significant relationships (P<0.01) with Wmax were obtained for age (r=-0.22), gender (r=0.45), fat free mass (FFM) (r=0.51), quadriceps muscle area (r=0.73), hamstrings muscle area (r=0.50), upper leg muscle function (i.e., a combination of muscle strength and muscle endurance) (r=0.71) and isometric strength (r=0.63). Multiple regression analysis showed that upper leg muscle function and quadriceps muscle area could predict 57% of the variance in Wmax., Conclusion: Muscle strength and muscle endurance, combined with quadriceps muscle area are the main predictors of maximal exercise performance in patients with CHF.

Approximately one in five top-level cyclists will develop sports-related flow limitations in the iliac arteries. These flow limitations may be caused by a vascular lumen narrowing due to endofibrotic thickening of the intima and/or by kinking of the vessels. In some athletes, extreme vessel length contributes to this kinking. Endofibrotic thickening is a result of a repetitive vessel damage due to haemodynamic and mechanical stress. Atherosclerotic intimal thickening is seldom encountered in these young athletes. This type of sports-related flow limitation shows no relationship with the classical risk factors for atherosclerosis like smoking, hypercholesterolaemia or family predisposition for arterial diseases. The patient's history is paramount for diagnosis. If an athlete reports typical claudication-like complaints in a leg at maximal effort, which disappear quickly at rest, approximately two out of three will have a flow limitation in the iliac artery. In current (sports) medical practice, this diagnosis is often missed, since a vascular cause is not expected in this healthy athletic population. Even if suspected, the routinely available diagnostic tests often appear insufficient. Definite diagnosis can be made by a combination of the patient's history and special designed tests consisting of a maximal cycle ergometer test with ankle blood pressure measurements and/or an echo-Doppler examination with provocative manoeuvres like hip flexion and exercise. Conservative treatment consists of diminishing or even completely stopping the provocative sports activity. If conservative treatment is insufficient or deemed unacceptable, surgical treatment might be considered. As surgery needs to be tailored to the underlying lesions, a detailed analysis before surgery is necessary. Standard clinical tests, used for visualising atherosclerotic diseases, are inadequate to identify and quantify the causes of flow limitations. Echo-Doppler examination and magnetic resonance angiography with both flexed and extended hips have been proven to be adequate tools. In particular, overprojection and eccentric location of the lesions seriously limit the usefulness of a two-dimensional technique like digital subtraction angiography. In the early stages, when kinking has not yet led to intimal thickening or excessive lengthening, simple surgical release of the iliac artery is effective. However, for patients with excessive vessel lengths or extensive endofibrotic thickening, a vascular reconstruction may be necessary. A major drawback of these interventions is that long-term effects and complications are unknown. As both the diagnostic methods and the treatments for this type of flow limitation differ substantially from routine vascular procedures, these patients should be examined in specialised research centres with appropriate diagnostic tools and medical experience.

Reduced levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are associated with deteriorated cognitive performance in senescence. Little work has been done on the effect of GH and IGF-1 on a crucial aspect of cognition, selective attention. This study investigated the effect of GH/IGF-1 on performance and brain potentials (EEG) during a selective-attention task in patients with low levels of GH and IGF-1 (childhood-onset growth hormone deficiency) compared to healthy controls. Detection of occasional visual target patterns was impaired in patients. This was paralleled by a reduction in an attention-related brain potential, which has been associated previously with anterior cingulate cortex functioning.

The aim of this study was to investigate the involvement of endogenous growth hormone-releasing hormone (GHRH) in the growth hormone (GH) release during strenuous exercise (EX). Eight healthy male subjects (age: 22.1 +/- 0.8 yr, body mass index: 22.2 +/- 0.9 kg/m 2, .VO 2 max: 52.2 +/- 0.5 ml/min/kg [mean +/- SEM]) were exposed to incremental EX until volitional exhaustion (cycle ergometry), and in random order to a maximally stimulating bolus injection of 100 microg GHRH, or to combined administration of 100 microg GHRH and EX (GHRH+EX). Serial blood samples in the fasted state were taken immediately before the start of each trial, and at appropriate intervals over 2 h. Total GH availability was calculated as area under the response curve (AUC), corrected for differences in baseline values. The results showed that peak serum GH levels to GHRH alone and EX alone were not significantly different: 41.5 +/- 9.0 microg/l and 64.1 +/- 8.1(mean +/- SEM). Peak GH level to GHRH+EX was 156.1 +/- 19.9 microg/l, which was significantly greater than to either stimulus alone (p < 0.02) or additively (105.6 +/- 17.1 microg/l, p < 0.02). AUC's to GHRH alone and EX alone were not significantly different (3242 +/- 839 vs. 2472 +/- 408 microg/l x 120 min). AUC to GHRH+EX (7807 +/- 1221 microg/l x 120 min) was greater than to either stimulus alone (p < 0.02) or additively (5714 +/- 1247 microg/l x 120 min, p < 0.02). This indicates a potentiating (synergistic) effect between GHRH and EX. We postulate that GH responses to strenuous EX are only partially due to maximal GHRH activation. Next to complete inhibition of hypothalamic somatostatin activity, which is achieved by strenuous exercise, activation of endogenous GH-releasing peptides, such as Ghrelin, must be operative.

Increased cardiovascular mortality due to premature atherosclerosis is a clinical feature in the adult-onset GH deficiency (AGHD) syndrome. Inflammation is a key feature in atherogenesis and may be triggered by postprandial lipoprotein remnants. We hypothesized that increased postprandial lipoprotein remnant levels in AGHD may be associated with an inflammatory response. In this case-control study, 10 AGHD patients [6 males and 4 females; age, 48 +/- 9 yr; body mass index (BMI), 26.9 +/- 2.6 kg/m(2)] and 10 healthy control subjects (matched for age, BMI, gender, baseline lipid levels, and apolipoprotein E genotype) were included. They all ingested an oral fat load. Fasting and postprandial levels of plasma remnant-like particle-cholesterol (RLP-C; 0.31 +/- 0.13 mmol/liter and 4.14 +/- 1.37 mmol/liter.h in GHD; 0.18 +/- 0.06 mmol/liter and 2.56 +/- 1.02 mmol/liter.h in controls, respectively) were significantly increased in AGHD patients compared with control subjects. The median inflammatory cytokines, IL-6 and TNF-alpha, were higher in the fasting [3.9 (range, 3.1-11.9) pg/ml and 6.8 (range, 2.5-27.6) pg/ml, respectively] and postprandial [151.7 (range, 87.0-294.3) pg/ml.24 h and 289.9 (range, 87.5-617.6) pg/ml.24 h, respectively] states in AGHD than in controls [fasting, 0.9 (range, 0.2-5.2) pg/ml and 2.8 (range, 2.5-5.7) pg/ml; and postprandial, 54.5 (range, 11.50-126.5) pg/ml.24 h and 118.3 (range, 81.2-243.1) pg/ml.24 h, respectively]. In addition, postprandial profile of RLP-C and IL-6 in AGHD and in the total group were significantly associated (r(2) = 0.44, P < 0.05; and r(2) = 0.38, P < 0.01, respectively). In conclusion, the increased postprandial RLP-C level in GHD is associated with an inflammatory response that may result in increased susceptibility for premature atherosclerosis.

Objective: Reduction of plasma free fatty acids leads to enhanced GH response after stimulation by GH-releasing hormone (GHRH). We studied the clinical usefulness of combined administration of acipimox and GHRH for the diagnosis of GH deficiency., Design: We evaluated 35 patients [mean age 53.0 years; mean body mass index (BMI) 26.7 kg/m2] after pituitary surgery. We compared GH responses after acipimox and GHRH with the GH response during an insulin tolerance test (ITT) and, in a subgroup of 12 patients, with the GHRH/arginine test. The acipimox/GHRH test was additionally performed in 21 control subjects (mean age 53.8 years; mean BMI 24.7 kg/m2)., Results: In the patients, the mean (+/- SEM) peak GH was almost four-fold higher after acipimox/GHRH (6.94 +/- 1.07 microg/l, range 0.46-23.1; P < 0.001) and after GHRH/arginine (8.32 +/- 1.23 microg/l, range 1.1-49.2; P < 0.001) than after ITT (1.84 +/- 0.46 microg/l, range 0.01-11.9). According to the ITT, 29 patients were severely GH deficient (peak GH < 3.0 microg/l). Peak GH levels after acipimox/GHRH in controls ranged from 7.5 to 78.4 microg/l (mean 29.3 +/- 3.5). GH peak values during the acipimox/GHRH test were significantly correlated with values from the ITT (r = 0.63, P < 0.01) and GHRH/arginine test (r = 0.87, P < 0.001). Areas under the curve were also correlated. According to generally accepted cut-off peak GH levels for the ITT and GHRH/arginine test, a GH peak exceeding 11.2 micro g/l excludes severe GH deficiency after acipimox/GHRH. Our control data indicate that the cut-off level is lower at older age., Conclusions: The acipimox/GHRH test leads to GH responses similar to those of the GHRH/arginine test, and to higher peak GH values if compared with the ITT. The acipimox/GHRH test is a potential additional tool to detect GH deficiency in patients with pituitary disease, in particular in patients with a perturbation of fatty acid metabolism.

The aim of this study was to investigate whether growth hormone (GH) release during strenuous exercise (EX) is due to complete inhibition of hypothalamic somatostatin (SS) activity. Eight healthy male subjects (age, 22.1 +/- 2.2 years; body mass index [BMI], 22.2 +/- 2.5 kg/m(2); maximum oxygen consumption [Vo(2)max], 52.2 +/- 1.5 mL/min/kg [mean +/- SD]) were exposed to strenuous EX on a cycle ergometer, with and without administration of pyridostigmine (PD), and to administration of PD alone. PD is an acetylcholine-esterase inhibitor that stimulates GH secretion by suppressing hypothalamic SS secretion and unmasking endogenous GH-releasing hormone (GHRH) tone. Serial blood samples in the fasted state were taken immediately before the start of each trial, and at appropriate intervals over 2 hours. GH responses were calculated as area under the response curve (AUC) by trapezoidal integration. The mean peak serum GH level to PD alone was 18.3 microg/L (range, 0.3 to 40.9), which was significantly lower than to EX alone: 64.1 microg/L (range, 30.5 to 90.5), and to the combined administration of PD and EX (PD+EX): 79.8 microg/L (range, 37.7 to 98.2) (P <.05). The arithmetic sum of the individual peak levels of 82.4 microg/L was not different from the mean peak level to PD+EX: 79.8 microg/L. AUC (mean +/- SEM) to PD alone (1,721 +/- 358 microg/L x 180 min) was not significantly different from that to EX alone (2,472 +/- 408 microg/L x 120 min), but was significantly lower than that to PD+EX: 3,526 +/- 752 (P <.05). Although the latter AUC was 6% smaller than the AUC obtained by arithmetic addition (3,747 +/- 706), this difference was not statistically significant. In conclusion, the additive effect between PD and EX indicates that PD and EX act independently in evoking GH responses to strenuous EX. Therefore, GH responses to strenuous EX are only partially due to complete inhibition of hypothalamic SS. Additional potentiating factors, such as activation of endogenous GHRH and ghrelin must be operative., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

The relationship was investigated between baseline serum levels of total testosterone (T), free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), ESTRADIOL (E2), sex hormone-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1) and cognitive functioning in 25 healthy older men (mean age 69.1 years). Cognitive tests concerned measures not sensitive to ageing (crystallized intelligence), and measures sensitive to ageing (fluid intelligence and verbal long-term memory). Partial correlation coefficients (controlled for level of education) revealed significant associations of total T (r = -.52, p = -.009), SHBG (r - .59, p = .002) and IGF-1 (r = .54, p = .007) with the composite measure of fluid intelligence test performance, but not with crystallized intelligence, nor verbal long-term memory. Stepwise hierarchical regression analysis with the composite measure of fluid intelligence as the dependent variable showed that the contributions of SHBG, total T, and IGF-1 were not additive.

This study examines the reproducibility of gastro-intestinal blood flow measurements in the superior mesenteric artery (SMA) both before and immediately after exercise with Doppler ultrasound measurements. Twelve well-trained males (mean +/- SD: age 25.9 +/- 3.8 yr; VO2max 4.8 +/- 0.91 x min(-1)) were measured twice (trial 1 and 2) with a 1 week interval before and immediately after 1 hr cycling at 70% VO2max. Duplex scanning was performed with the athletes in supine position immediately after transition from a chair (before exercise) or bicycle (after exercise). The variability of three measurements before exercise was studied within both trials (short-term reproducibility) and the mean pre-exercise values were compared between the trials (long-term reproducibility). In addition, post-exercise measurements were compared in the same way. Reproducibility was tested using the coefficient of variation and Cronbach's alpha. Mean pre-exercise blood flow was 424 +/- 66 ml/min (n = 12) in trial 1 and 375 +/- 38 ml/min (n = 11) in trial 2. Immediately after exercise blood flow had decreased by 49% to 214 +/- 36 ml/min (p <0.01) in trial 1 and by 38% to 234 +/- 36 ml/min (p < 0.01) in trial 2. Blood flow before and after exercise was not significantly different between trials (paired t-test) and therefore reproducible at the group level. Before exercise a good to fair reproducibility was observed both at the short-term (Cronbach's alpha: 0.88 in trial 1, 0.73 in trial 2, n = 11), and at the long-term (alpha = 0.80, n= 11). In contrast, long-term reproducibility immediately after exercise was poor (alpha = -0.99, n = 8 and alpha = 0.36, n = 7 after the first and second cycling period, respectively). In conclusion, duplex scanning of SMA after a sitting-supine transition in well-trained subjects is not a reproducible method at the individual level for intestinal blood flow measurements immediately after exercise.

This review describes the current state of knowledge on the hazards of exercise and the potential benefits of physical activity on the gastrointestinal tract. In particular, acute strenuous exercise may provoke gastrointestinal symptoms such as heartburn or diarrhoea. A substantial part (20-50%) of endurance athletes are hampered by these symptoms which may deter them from participation in training and competitive events. Nevertheless, these acute symptoms are transient and do not hamper the athlete's health in the long term. The only exception is repeated gastrointestinal bleeding during training and competition, which in the long term may occasionally lead to iron deficiency and anaemia. In contrast, repetitive exercise periods at a relatively low intensity may have protective effects on the gastrointestinal tract. There is strong evidence that physical activity reduces the risk of colon cancer by up to 50%. Less convincing evidence exists for cholelithiasis and constipation. Physical activity may reduce the risk of diverticulosis, gastrointestinal haemorrhage, and inflammatory bowel disease although this cannot be substantiated firmly. Up to now, underlying mechanisms are poorly understood although decreased gastrointestinal blood flow, neuro-immuno-endocrine alterations, increased gastrointestinal motility, and mechanical bouncing during exercise are postulated. Future research on exercise associated digestive processes should give more insight into the relationship between physical activity and the function of the gastrointestinal tract.

GH release is increased by reducing circulating free fatty acids (FFAs). Aging is associated with decreased plasma GH concentrations. We evaluated GH releasing capacity in nine healthy elderly men after administration of GH-releasing peptide 2 (GHRP-2), with or without pretreatment with the antilipolytic drug acipimox, and compared the GHRP-2-induced GH release with the response to GHRH. The area under the curve (AUC) of the GH response after GHRP-2 alone was 4.8 times higher compared with GHRH alone (1834 +/- 255 vs. 382 +/- 78 microg/L.60 min, P: < 0.001). Acipimox, which reduced FFAs from 607 micromol/L to 180 micromol/L, increased the GH AUC to 1087 after GHRH and to 2956 microg/L.60 min after GHRP-2 (P: < 0.01). The AUC after acipimox/GHRP-2 were positively correlated with the AUC after GHRP-2 alone (r = 0.93, P: < 0.01); this was also observed between acipimox/GHRH and GHRH alone (r = 0.73, P: = 0.03). Significant negative correlations were observed between basal FFAs and AUC after GHRH or GHRP-2 after combining the data with and without acipimox (r = 0.58, P: = 0.01 and r = 0.48, P: = 0.04, respectively), and between basal FFAs and GH at t = 0 (r = -0.44, P: = 0.001). Interestingly, GHRP-2 administration was followed by a significant early rise in plasma FFAs by 60% (P = 0.01), indicating an acute lipolytic effect. In conclusion, reduction of circulating FFAs strongly enhances GHRP-2-stimulated GH release in elderly men. The data indicate that the decreased GH release associated with aging can be reversed by acipimox and that the pituitary GH secretory capacity in elderly men is still sufficient.

Objective: Responses to stressful events are generally regarded as reactions of the organism to accommodate to or compensate for stress. This reaction is classically described as an activation of the sympathoadrenal system and the hypothalamic-pituitary-adrenocortical (HPA) axis. Activation of the release of growth hormone and prolactin in blood also occurs during various types of stress. Assuming that the stress response is a neuroendocrine mechanism that occurs in anticipation of physical exercise, we investigated whether an incremental exercise protocol can be used as a model stressor to disclose a distinct pattern of activation in these hormonal systems, which would support the notion that these systems have different roles in preparing the organism for physical activity and recovery. Moreover, such a model may help improve our understanding of the endocrine expressions of psychological stress., Methods: After an overnight fast, 8 healthy men (age, 19-26 years) cycled at 40, 60, 80, and 100% of the power output at VO2max in successive time blocks of 10 minutes each up to exhaustion. Venous blood was sampled immediately before exercise, at the end of each block, and during the recovery phase 5 and 30 minutes after exercise. Plasma adrenalin and noradrenalin were measured by high-performance liquid chromatography; plasma adrenocorticotropic hormone, beta-endorphin, cortisol, growth hormone, and prolactin were measured by specific immunoassays. Heart rate and levels of blood lactate and adrenalin were measured as markers of workload-related responses., Results: Results showed that increases in heart rate, lactate, adrenalin, noradrenalin, and growth hormone reflected the relative workload, in contrast to increases in adrenocorticotropic hormone, beta endorphin, and prolactin, which were observed only after exercise reached an intensity of 80% VO2max. Increases in cortisol were found just after exhaustion. The delayed response of cortisol may be initiated by a drop in blood glucose levels but may also be considered preparatory to vigorous muscular effort and protective against tissue damage., Conclusions: Measurement of the cumulative response to exercise shows that activation of stress hormones occurs at different time points, supporting the notion that these hormones have different roles in preparing the organism for physical activity and recovery: ie, workload- and effort-related adaptation on one hand and protection against disturbed homeostasis on the other. The delayed response of the HPA axis during incremental exercise contrasts with the nondelayed HPA axis response observed during psychological stress and points to involvement of different neurobiological and cognitive emotional mechanisms.

In adult growth hormone deficiency (GHD) syndrome responsiveness to GH replacement therapy is reported to vary considerably. The underlying mechanisms, however, are not well understood. The aim of this study was to investigate which baseline variables determine the reported variable intersubject responsiveness of high-affinity GH-binding protein (GHBP) to GH replacement therapy. In the setting of a double blind study over 12 months with placebo control over the first 6 months, we analyzed the interrelationship between a number of baseline variables, which vary considerably amongst subjects, and the GHBP response to GH replacement in 31 GHD adults (21 males and 10 females). The following variables were investigated: age, gender, duration of GHD, body composition, serum levels of high-affinity GHBP, insulin-like growth factor-1 (IGF-1), and IGF-binding protein-3 (IGFBP-3). The results showed that in the 6 months treated group of 16 patients (11 males, 5 females), serum IGF-1 increased from 87 ng/ml (range: 26 to 173) to 250 (range: 62 to 467) (p<0.01) and GHBP increased from 1,302 pmol/l (range: 845 to 1,m960) to 1418 (range: 941 to 2,025) (p=0.04). Both parameters showed a significant time effect (within-subjects) (p<0.001). In the 12 months treated group of 15 patients (10 males, 5 females), serum IGF-1 increased from 92 ng/ml (range: 20 to 180) to 272 (range: 45 to 491) (p<0.01), whereas GHBP did not show a significant change: from 1,186 pmol/l (range: 660 to 1,690) to 1,252 (range: 580 to 1,890) (p=0.87). Also no significant time effect (within-subjects) was observed for GHBP (p=0.06). Step-wise multiple regression analyses revealed that during the 6 months placebo period baseline GHBP explained 83% of the variance in post-placebo GHBP, whereas the variance in post-treatment GHBP could be accurately predicted (adjusted R2=0.93) from baseline GHBP and body fat mass, irrespective of the duration of GH treatment. No other baseline variables contributed independently to the GHBP response, with the exception of IGFBP-3, which showed a small, but significant contribution in females, but not in males. These findings indicate that the variable intersubject responsiveness of GHBP to GH replacement therapy is mainly due to differences in baseline body fat mass amongst adult GHD patients, and that in female patients a relatively low baseline IGFBP-3 contributes to a rise in serum GHBP after GH treatment. The clinical relevance of measuring GHBP in adult GHD patients is limited to the first screening step to diagnose GHD, because long-term GH therapy tends to restore serum GHBP to pretreatment levels.