Skeletal muscle catabolism at high-altitude--immunoprotective or immunodepressive?
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Biomedical subjects
Publications and source records attributed to D M Bailey.
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Indices of mechanical power output were obtained from twelve subjects during high intensity leg cycle ergometry tests (20 second duration; 75 grams per kilogram total body mass) using two protocols: one with a standard handle-bar grip (with-grip), and one with supinated wrists (without-grip). Peak mechanical power, mean mechanical power, fatigue index and total mechanical work values were calculated for each subject during each test, and the sample mean differences associated with the two protocols were compared using paired Student t-tests. The with-grip protocol yielded significantly greater peak mechanical power output and greater fatigue index than the without-grip protocol (886 +/- 124W and 815 +/- 151W, respectively; and 35 +/- 10% and 25 +/- 8%, respectively; p<0.01). The electrical activity of the anterior forearm musculature was measured in the twelfth subject during the performance of each of the test protocols. While peak mechanical power output was greater during the with-grip protocol, than during the without-grip protocol, the electromyographs showed much greater forearm muscle activity during the with-grip protocol. Thus the protocol which allowed for the greatest measure of peak leg power output was also associated with considerable arm muscle activity. These findings should be considered when biochemical and physiological measurements are obtained from arm blood samples.
OBJECTIVES: To examine the prostates from patients with haematuria associated with benign prostatic hyperplasia (BPH) to determine their microvascular anatomy and thus assess histopathological differences in patients with significant haematuria. PATIENTS AND METHODS: Prospectively, 11 patients with BPH and haematuria (mean age 70 years) and 19 control patients with BPH alone (mean age 72 years) were identified. Neither group had received hormone manipulation or had been catheterized. The sub-urothelial compartment of the prostatic urethra in subsequent specimens from transurethral resection was examined using factor VIII/CD-34 immuno-histochemistry. The microvessel density (MVD) was calculated by counting vascular cross-sectional profiles within a 0.81-mm2 grid. The pathologist studying the specimens was unaware of the patients' symptoms. RESULTS: The median (range) MVD in the haematuria group was 64 (28-137) and in the controls was 27 (14-39) (P < 0.001). CONCLUSION: The MVD was significantly greater in the patients with haematuria, suggesting that suburothelial microvessel proliferation may play an important role in mediating haematuria associated with BPH. This is the first time that a difference has been shown at the cellular level in patients with haematuria and could form an important foundation for subsequent research.
The aims of the present study were to measure the satiety neuropeptide cholecystokinin (CCK) in humans at terrestrial high altitude to investigate its possible role in the pathophysiology of anorexia, cachexia, and acute mountain sickness (AMS). Nineteen male mountaineers aged 38 +/- 12 years participated in a 20 +/- 5 day trek to Mt. Kanchenjunga basecamp (BC) located at 5,100 m, where they remained for 7 +/- 5 days. Subjects were examined at rest and during a maximal exercise test at sea-level before/after the expedition (SL1/SL2) and during the BC sojourn. There was a mild increase in Lake Louise AMS score from 1.1 +/- 1.2 points at SL1 to 2.3 +/- 2.3 points by the end of the first day at BC (P < 0.05). A marked increase in resting plasma CCK was observed on the morning of the second day at BC relative to sea-level control values (62.9 +/- 42.2 pmol/L(-1) vs. SL1: 4.3 +/- 8.3 pmol/L(-1), P < 0.05 vs. SL2: 26.5 +/- 25.2 pmol/L(-1), P < 0.05). Maximal exercise increased CCK by 78.5 +/- 24.8 pmol/L(-1), (P < 0.05 vs. resting value) during the SL1 test and increased the plasma concentration of non-esterified fatty acids and glycerol at BC (P < 0.05 vs. SL1/SL2). The CCK response was not different in five subjects who presented with anorexia on Day 2 compared with those with a normal appetite. While there was no relationship between the increase in CCK and AMS score at BC, a more pronounced increase in resting CCK was observed in subjects with AMS (> or =3 points at the end of Day 1 at BC) compared with those without (+98.9 +/- 1.4 pmol/L(-1) vs. +67.6 +/- 37.2 pmol/L(-1), P < 0.05). Caloric intake remained remarkably low during the stay at BC (8.9 +/- 1.4 MJ.d(-1)) despite a progressive decrease in total body mass (-4.5 +/- 2.1 kg after 31 +/- 13 h at BC, P < 0.05 vs. SL1/SL2), which appeared to be due to a selective loss of torso adipose tissue. These findings suggest that the satiogenic effects of CCK may have contributed to the observed caloric deficit and subsequent cachexia at high altitude despite adequate availability of palatable foods. The metabolic implications of elevated CCK in AMS remain to be elucidated.
PURPOSE: This study was designed to determine changes in metabolic and cardiovascular risk factors following normobaric hypoxic exercise training in healthy men. METHODS: Following a randomized baseline maximal exercise test in hypoxia and/or normoxia, 34 physically active subjects were randomly assigned to either a normoxic (N = 14) or a hypoxic (N = 18) training group. Training involved 4 wk of cycling exercise inspiring either a normobaric normoxic (F(IO2) = approximately 20.9%) or a normobaric hypoxic (F(IO2) = approximately 16.0%) gas, respectively, in a double-blind manner. Cycling exercise was performed three times per week for 20-30 min at 70-85% of maximum heart rate determined either in normoxia or hypoxia. Resting plasma concentrations of blood lipids, lipoproteins, total homocysteine, and auscultatory arterial blood pressure responses at rest and in response to submaximal and maximal exercise were measured before and 4 d after physical training. RESULTS: Total power output during the training period was identical in both normoxic and hypoxic groups. Lean body mass increased by 1.4 +/- 1.5 kg following hypoxic training only (P < 0.001). While dietary composition and nutrient intake did not change during the study, both normoxic and hypoxic training decreased resting plasma concentrations of nonesterified fatty acids, total cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) (P < 0.05 - < 0.001). Apolipoproteins AI and B decreased following normoxic training only (P < or = 0.001). Plasma concentrations of resting total homocysteine decreased by 11% following hypoxic training (P < or = 0.05) and increased by 10% (P < 0.05) following normoxic training. These changes were independent of changes in serum vitamin B12 and red cell folate which remained stable throughout. A decreased lactate concentration during submaximal exercise was observed in response to both normoxic and hypoxic training. Hypoxic training decreased maximal systolic blood pressure by 10 +/- 9 mm Hg (P < 0.001) and the rate pressure product by 14 +/- 23 mm Hg x beats x min(-1)/100 (P < or = 0.001) and increased maximal oxygen uptake by 0.47 +/- 0.77 L x min(-1) (P < 0.05). CONCLUSION: Normoxic and hypoxic training was associated with significant improvements in selected risk factors and exercise capacity. The stimulus of intermittent normobaric hypoxia invoked an additive cardioprotective effect which may have important clinical implications.
OBJECTIVE: Despite recently published national guidelines, many physicians have only limited knowledge about Helicobacter pylori infection. We conducted this study to assess internal medicine residents' knowledge about H. pylori. METHODS: Two hundred and nineteen residents in seven accredited internal medicine training programs completed a self-administered questionnaire on personal demographics and practices related to testing for-and treating-H. pylori infection. RESULTS: Noon conferences (82%), ward teaching (66%), journals (70%), and sponsored symposia (27%) were their major sources of H. pylori-related information. Forty-eight percent had used office-based tests for the infection. Testing for (and treatment of) Helicobacter pylori infection was recommended by 97% (97%) for newly diagnosed duodenal ulcer, but by only 61% (63%) for a past history of duodenal ulcer. Many recommended testing in unproven conditions and might not have offered treatment to an infected patient. A proton pump inhibitor-based triple-drug regimen was the treatment of first choice of 55%; 20% recommended proton pump inhibitor-based dual regimens. Sixty-six percent and 80%, respectively, underestimated the rates of resistance to clarithromycin and metronidazole. In the absence of gastrointestinal symptoms, 22% would have ordered Helicobacter pylori testing but only 33% of these would undergo treatment if positive. CONCLUSIONS: Internal medicine residents usually test for Helicobacter pylori infection in appropriate conditions, but may not always treat the infection when the result is positive. Most use efficacious treatment regimens although many have inaccurate knowledge of resistance rates, which may adversely influence prescribing. Education should focus on practical issues surrounding Helicobacter pylori testing and treatment such as those contained in the American College of Gastroenterology's 1998 practice guidelines.
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Cardiovascular function was determined at rest and during exercise in twenty-eight healthy, elite distance runners. Maximum heart rate was 184 +/- 6 b x min(-1), which was more than one SD lower than the age predicted value (p < 0.001), and an inverse correlation was observed between maximum heart rate and VO2max (r = - 0.82, p < 0.001). The most aerobically trained athlete, a 27 year old male, presented with a maximum heart rate of 139b x min(-1). Echo-cardiac ultrasound revealed unremarkable intra-cardiac dimensions and flow characteristics relative to other endurance-trained athletes. A decreased chronotropic drive may represent a favourable physiological adaptation to endurance exercise which increases cardiovascular efficiency.
This case study reports the clinical and physiological changes of a 33 year old elite marathoner undertaking intensive endurance training during and following a twin pregnancy. Prior to conception, the subject ran 155 km x week(-1) at an intensity equivalent to 140-180 b x min(-1) which following consultation decreased to 107 +/- 19 km x week(-1) at an intensity equivalent to 130-140 b x min(-1) during pregnancy. Physical exercise ceased 3 days prior to an elective Caesarean section following a 36 week gestation period and recommenced 8 days following the birth of healthy twins. Medical assessments conducted ante/post partum indicated that both the twins and mother were healthy. A field based test demonstrated that running velocity at a steady state HR of 140 b x min(-1), 150 b x min(-1) and 160 b x min(-1) decreased by 20%, 15% and 13% respectively between weeks 1 and 32 antepartum. Whole blood lactate ([La-]B), oxygen uptake (VO2), ventilatory equivalent for oxygen (V(E)/VO2), HR and Borg rating of perceived exertion (RPE) increased during a laboratory-based submaximal treadmill test at 29 weeks antepartum in comparison to a test conducted 10 weeks post partum. These data clearly demonstrate that it is possible for an elite endurance athlete to maintain a high level of cardiovascular fitness during pregnancy with no apparent adverse effects on maternal or foetal health. This will facilitate an earlier return to international competition.
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Elite distance runners participated in one of two studies designed to investigate the effects of moderate altitude training (inspiratory partial pressure of oxygen approximately 115-125 mmHg) on submaximal, maximal and supramaximal exercise performance following return to sea-level. Study 1 (New Mexico, USA) involved 14 subjects who were assigned to a 4-week altitude training camp (1500-2000 m) whilst 9 performance-matched subjects continued with an identical training programme at sea-level (CON). Ten EXP subjects who trained at 1640 m and 19 CON subjects also participated in study 2 (Krugersdorp, South Africa). Selected metabolic and cardiorespiratory parameters were determined with the subjects at rest and during exercise 21 days prior to (PRE) and 10 and 20 days following their return to sea-level (POST). Whole blood lactate decreased by 23% (P < 0.05 vs PRE) during submaximal exercise in the EXP group only after 20 days at sea-level (study 1). However, the lactate threshold and other measures of running economy remained unchanged. Similarly, supramaximal performance during a standardised track session did not change. Study 2 demonstrated that hypoxia per se did not alter performance. In contrast, in the EXP group supramaximal running velocity decreased by 2% (P < 0.05) after 20 days at sea-level. Both studies were characterised by a 50% increase in the frequency of upper respiratory and gastrointestinal tract infections during the altitude sojourns, and two male subjects were diagnosed with infectious mononucleosis following their return to sea-level (study 1). Group mean plasma glutamine concentrations at rest decreased by 19% or 143 (74) microM (P < 0.001) after 3 weeks at altitude, which may have been implicated in the increased incidence of infectious illness.
OBJECTIVE: To assess the histological changes found in patients with long-term external sphincter, prostatic and urethral stents. PATIENTS AND METHODS: Eighteen patients with long-term stents (mean time since insertion 3.5 years) were investigated. Three had external sphincter stents for detrusor-sphincter dyssynergia secondary to spinal injury, eight had prostatic stents for obstruction secondary to benign prostatic hyperplasia and seven had urethral stents for recurrent strictures. Nine stents were occluded at investigation, of which seven were entirely removed. The mucosae overlying the remaining two were biopsied, as were mucosae over the nine patent stents, at urethroscopy. RESULTS: The changes observed included polypoid hyperplasia (11 of 18 patients) between and around the stent mesh wires, nonkeratinizing squamous metaplasia (two) or hyperkeratotic squamous metaplasia (seven), chronic inflammation (15) with prominent plasma cell infiltrates (11), variable foreign-body granuloma (two) and microabscess formation (five), usually associated with clefts formed around the stent wires (three of five). CONCLUSION: Stents become incorporated into the urethral wall by a process of polypoid hyperplasia through the stent mesh, with at least focal covering of the stent in most cases, and with variable inflammatory infiltrates, most of which are rich in plasma cells. The urothelial and connective tissue proliferation resulted in obstruction of the stent lumen in nine of the patients studied. Further long-term study is necessary to exclude the development of carcinoma in patients with keratinizing squamous metaplasia, although no malignancy was seen in this study.
The asplenia [Ivemark] syndrome (AS) is the association of congenital absence of the spleen with a variety of visceral abnormalities, predominantly of the cardiovascular system. Varying degrees of malrotation and malfixation of the bowel are common in this condition, and the occurrence of catastrophic gastric volvulus due to malfixation of the bowel has been reported. With the improvement in long-term outlook for these patients with modern cardiac surgery and prophylactic antibiotics, the intra-abdominal anomalies have become increasingly significant. This paper draws attention to the prophylactic treatment of gastric malfixation in the AS through the presentation of two cases in which gastropexy was performed.
OBJECTIVES: This investigation was designed to monitor altitude acclimatisation in an elite cohort of distance runners and follow the subsequent recovery from infectious mononucleosis which developed in one of these athletes. METHODS: Twenty six national standard distance runners performed treadmill tests 24 days before they travelled to an altitude camp (1500 to 2000 m). One of these athletes was diagnosed as suffering from infectious mononucleosis 14 days after return to sea level. A physician prescribed an individualised training programme which was designed to maximise recovery from the condition, which was monitored on days 16 and 147 after altitude training. RESULTS AND CONCLUSIONS: The data suggest that the athlete was in a state of over-reaching during the altitude sojourn. After return to sea level, the early stages of infectious mononucleosis resulted in a marked impairment in physiological response to endurance exercise, which improved over time. Longitudinal physiological monitoring in conjunction with a carefully prescribed training programme made recovery from this condition possible.
Acclimatisation to environmental hypoxia initiates a series of metabolic and musculocardio-respiratory adaptations that influence oxygen transport and utilisation, or better still, being born and raised at altitude, is necessary to achieve optimal physical performance at altitude, scientific evidence to support the potentiating effects after return to sea level is at present equivocal. Despite this, elite athletes continue to spend considerable time and resources training at altitude, misled by subjective coaching opinion and the inconclusive findings of a large number of uncontrolled studies. Scientific investigation has focused on the optimisation of the theoretically beneficial aspects of altitude acclimatisation, which include increases in blood haemoglobin concentration, elevated buffering capacity, and improvements in the structural and biochemical properties of skeletal muscle. However, not all aspects of altitude acclimatisation are beneficial; cardiac output and blood flow to skeletal muscles decrease, and preliminary evidence has shown that hypoxia in itself is responsible for a depression of immune function and increased tissue damage mediated by oxidative stress. Future research needs to focus on these less beneficial aspects of altitude training, the implications of which pose a threat to both the fitness and the health of the elite competitor. Paul Bert was the first investigator to show that acclimatisation to a chronically reduced inspiratory partial pressure of oxygen (P1O2) invoked a series of central and peripheral adaptations that served to maintain adequate tissue oxygenation in healthy skeletal muscle, physiological adaptations that have been subsequently implicated in the improvement in exercise performance during altitude acclimatisation. However, it was not until half a century later that scientists suggested that the additive stimulus of environmental hypoxia could potentially compound the normal physiological adaptations to endurance training and accelerate performance improvements after return to sea level. This has stimulated an exponential increase in scientific research, and, since 1984, 22 major reviews have summarised the physiological implications of altitude training for both aerobic and anaerobic performance at altitude and after return to sea level. Of these reviews, only eight have specifically focused on physical performance changes after return to sea level, the most comprehensive of which was recently written by Wolski et al. Few reviews have considered the potentially less favourable physiological responses to moderate altitude exposure, which include decreases in absolute training intensity, decreased plasma volume, depression of haemopoiesis and increased haemolysis, increases in sympathetically mediated glycogen depletion at altitude, and increased respiratory muscle work after return to sea level. In addition, there is a risk of developing more serious medical complications at altitude, which include acute mountain sickness, pulmonary oedema, cardiac arrhythmias, and cerebral hypoxia. The possible implications of changes in immune function at altitude have also been largely ignored, despite accumulating evidence of hypoxia mediated immunosuppression. In general, altitude training has been shown to improve performance at altitude, whereas no unequivocal evidence exists to support the claim that performance at sea level is improved. Table 1 summarises the theoretical advantages and disadvantages of altitude training for sea level performance. This review summarises the physiological rationale for altitude training as a means of enhancing endurance performance after return to sea level. Factors that have been shown to affect the acclimatisation process and the subsequent implications for exercise performance at sea level will also be discussed. Studies were located using five major database searches, which included Medline, Embase, Science Citation Index, Sports Discus, and Sport, in