Weaving for the future: using rulers and roses.
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Evidence-Based Medicine↗
Biomedical subjects
B Davies
Publications and source records attributed to B Davies.
A potential role for free radical-mediated skeletal muscle soreness in the pathophysiology of acute mountain sickness.
BACKGROUND: It has been suggested that free radicals may be implicated in the pathophysiology of acute mountain sickness (AMS) due to their ability to initiate and propagate cell membrane damage (3). Therefore, the present study was designed to: a) investigate the effects of an expedition to high altitude on metabolic indices of free radical-mediated oxidative stress and assess subsequent implications for skeletal/cardiac muscle damage; and b) determine whether these parameters were different in subjects who developed AMS after gradual ascent to 5100 m (base camp, BC) compared with those who remained healthy. METHODS: There were 19 male volunteers who were examined at rest and after a standardized maximal exercise test at sea level before and after an expedition (SL1/SL2) and during the first morning of arrival at BC. The trek to BC lasted 20+/-5 d. RESULTS: A mild increase in the Lake Louise AMS score was observed by the end of day 1 at BC (p < 0.05 vs. SL1/SL2). Four subjects developed AMS, which in one subject later progressed to high altitude pulmonary and cerebral edema. The serum concentration of lipid hydroperoxides (LH) increased markedly at rest and after maximal exercise at BC (p < 0.05 vs. SL1/SL2) whereas no changes were observed for plasma malondialdehyde (MDA). Resting serum total phosphocreatine kinase activity (CPK) and myoglobin also increased at BC (p < 0.05 vs. SL1/SL2) whereas cardiac troponin I (cTnI) remained stable. The resting pain threshold decreased and exercise-induced muscle soreness subsequently increased at BC (p < 0.05 vs. SL1/SL2). An association was observed between resting LH and myoglobin at BC (r = 0.45, p < 0.05) and the increase in LH was related to the increase in exercise-induced muscle soreness at BC (r = 0.96, p < 0.05). Further correlations were identified between the AMS score on day 1 at BC and: a) resting/exercise LH (r = 0.63, p < 0.05/r = 0.51, p < 0.05); and b) resting pain threshold at BC (r = -0.58, p < 0.05). Furthermore, subjects with AMS on day 1 at BC were characterized by a greater decrease in the resting pain threshold and greater increase in resting LH, CPK and myoglobin compared with subjects without AMS (p < 0.05). Headache, fatigue, insomnia and general apathy were the most frequently reported symptoms of AMS. CONCLUSIONS: Localized free radical-mediated vascular damage of the blood-brain barrier in addition to systemic tissue damage causing overt skeletal muscle soreness may have contributed to the pathophysiology of AMS, the latter through its indirect effects on other non-specific constitutional symptoms such as fatigue and insomnia causing a deterioration in physical performance.
Acute Disease↗
Intermittent hypoxic training: implications for lipid peroxidation induced by acute normoxic exercise in active men.
Oxidant generation during regular physical exercise training may influence the adaptive responses that have been shown to confer protection against oxidative stress induced by subsequent acute exercise. To examine this, we randomly assigned 32 males to either a normoxic (n=14) or a hypoxic (n=18) group. During the acute phase, subjects in the hypoxic group performed two maximal cycling tests in a randomized double-blind fashion: one under conditions of normoxia and the other under hypoxic conditions (inspired fraction of O(2)=0.21 and 0.16 respectively). During the intermittent phase, the normoxic and hypoxic groups each trained for 4 weeks at the same relative exercise intensity, under conditions of normoxia and hypoxia respectively. During acute exercise under hypoxic conditions, the venous concentrations of lipid hydroperoxides and malondialdehyde were increased, despite a comparatively lower maximal oxygen uptake (VO(2max)) (P<0.05 compared with normoxia). The increases in lipid hydroperoxides and malondialdehyde were correlated with the exercise-induced decrease in arterial haemoglobin oxygen saturation (r=-0.61 and r=-0.50 respectively; P<0.05), but not with VO(2max). Intermittent hypoxic training attenuated the increases in lipid hydroperoxides and malondialdehyde induced by acute normoxic exercise more effectively than did normoxic training, due to a selective mobilization of alpha-tocopherol (P<0.05). The latter was related to enhanced exercise-induced mobilization/oxidation of blood lipids due to a selective increase in VO(2max) (P<0.05 compared with normoxic group). We conclude that lipid peroxidation induced by acute exercise (1) increases during hypoxia; (2) is not regulated exclusively by a mass action effect of VO(2); and (3) is selectively attenuated by regular hypoxic training. Oxidative stress may thus be considered as a biological prerequisite for adaptation to physical stress in humans.
Adult↗
Beyond the ABCs: ternary complex formation in the control of floral organ identity.
The production of a flower requires several events to occur. A floral meristem must form, boundaries must be set to enable discrete primordia to arise and the primordia must adopt the correct organ identity. Homeotic mutants, whose organs adopt inappropriate identities for their position within the flower, have helped the construction of a simple combinatorial model to explain how floral organ identity is defined. However, recent experiments suggest that the regulation of floral organ identity is more complex than was previously apparent. The simple interactions are becoming more complex and the universal applicability of the model less clear.
Arabidopsis↗
Power output of legs during high intensity cycle ergometry: influence of hand grip.
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.
Adult↗
Elevated plasma cholecystokinin at high altitude: metabolic implications for the anorexia of acute mountain sickness.
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.
Adult↗
Insulin-like growth factor I increases follicle-stimulating hormone (FSH) content and gonadotropin-releasing hormone-stimulated FSH release from coho salmon pituitary cells in vitro.
The effects of insulin-like growth factor I (IGF-I) and insulin on the function of coho salmon gonadotropes in vitro were investigated. Dispersed pituitary cells from immature coho salmon (Oncorhynchus kisutch) were incubated with IGF-I for 1, 3, 7, or 10 days, then incubated with salmon GnRH for an additional 24 h. Medium FSH content before and after GnRH treatment and intracellular FSH content after GnRH treatment were measured. Incubation of pituitary cells with IGF-I for 7 or 10 days increased GnRH-stimulated FSH release and remaining cell content, but did not affect basal release. To examine the specificity of the effects of IGF-I, we compared FSH release and cell content of FSH and LH after 10-day incubation with a range of concentrations of IGF-I or insulin. Incubation with physiological concentrations of IGF-I resulted in significantly higher GnRH-stimulated FSH release and remaining cell content of FSH and LH. Conversely, supraphysiological concentrations of insulin were required to produce more moderate effects on gonadotropin levels. These results suggest that elevation of gonadotropin levels by IGF-I may be one mechanism by which somatic growth and nutrition promote pubertal development in salmon.
Animals↗
Facilitating day-to-day decision making in palliative care.
As part of a larger grounded theory study investigating the process by which palliative care patients make everyday choices, a secondary analysis of data was conducted to investigate the ways nurses support or restrict patients' participation in their care. Constant comparative methods were used to generate a detailed, contextually grounded description of nurses' strategies that influenced patients' participation in making everyday choices about their personal and nursing care. Data consisted of field notes derived from observations of patients and their caregivers in two hospital-based palliative care units and from 23 transcripts of interviews with participating nurses and patients. Nurses' efforts to support patients' participation in decision making were described as a four-phase process: getting to know the patient, enhancing opportunities for choice, being open to patient choice, and respecting choice. Factors influencing nurses' use of supportive behaviors and behaviors that restricted patients' participation in everyday choices were identified. Given the importance patients attributed to making choices, these findings provide a foundation for the design of nursing interventions that hold great potential for directly influencing quality of life.
Adult↗
Training in hypoxia: modulation of metabolic and cardiovascular risk factors in men.
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.
Adult↗
Continuous and intermittent exposure to the hypoxia of altitude: implications for glutamine metabolism and exercise performance.
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Adaptation, Physiological↗
A review of robotics in surgery.
A brief introduction is given to the definitions and history of surgical robotics. The capabilities and merits of surgical robots are then contrasted with the related field of computer assisted surgery. A classification is then given of the various types of robot system currently being investigated internationally, together with a number of examples of different applications in both soft-tissue and orthopaedic surgery. The paper finishes with a discussion of the main difficulties facing robotic surgery and a prediction of future progress.
Equipment Safety↗
ROBO-SIM: a simulator for minimally invasive neurosurgery using an active manipulator.
This application report describes the software system ROBO-SIM, which is a planning and simulation tool for minimally invasive neurosurgery. Using actual patient's datasets, ROBO-SIM includes all planning steps necessary. These are; defining the trepanation point for entry into the skull and the target point within the depth of the brain, checking the surgical track, performing virtual trepanations (virtual craniotomy), and defining sanctioned volumes for use with an intra-operative active manipulator. With the additional simulation part, neurosurgeons are able to simulate whole surgical interventions directly on the patient's anatomy using the same instruments as for the real operation. First tests with ROBO-SIM are performed on actual patient's datasets with ventricular tumours.
Computer Simulation↗
PLENA and FARINELLI: redundancy and regulatory interactions between two Antirrhinum MADS-box factors controlling flower development.
We report the discovery of an Antirrhinum MADS-box gene, FARINELLI (FAR), and the isolation of far mutants by a reverse genetic screen. Despite striking similarities between FAR and the class C MADS-box gene PLENA (PLE), the phenotypes of their respective mutants are dramatically different. Unlike ple mutants, which show homeotic conversion of reproductive organs to perianth organs and a loss of floral determinacy, far mutants have normal flowers which are partially male-sterile. Expression studies of PLE and FAR, in wild-type and mutant backgrounds, show complex interactions between the two genes. Double mutant analysis reveals an unexpected, redundant negative control over the B-function MADS-box genes. This feature of the two Antirrhinum C-function-like genes is markedly different from the control of the inner boundary of the B-function expression domain in Arabidopsis, and we propose and discuss a model to account for these differences. The difference in phenotypes of mutants in two highly related genes illustrates the importance of the position within the regulatory network in determining gene function.
Amino Acid Sequence↗
The brain-pituitary-gonadal axis of female rainbow trout Oncorhynchus mykiss: effects of photoperiod manipulation1.
Two groups of post-spawned female rainbow trout were exposed to two different photoperiods, an ambient photoperiod (56 degrees N) and a combination of long and short photoperiods (a constant 18L:6D from February 1 until May 10, then a constant 6L:18D), which acted to advance maturation and spawning. The stimulatory long-short photoperiod advanced spawning by 3-4 months and correspondingly advanced peaks in serum levels of 17beta-estradiol, testosterone, calcium (an index of vitellogenin), and GTH II. Earlier events in gonadal recrudescence appeared to be less affected by the photoperiod. The initiation of exogenous vitellogenesis coincided with high levels of both pituitary salmon gonadotropin-releasing hormone (sGnRH) content and serum follicle-stimulating hormone (FSH, GTH I) levels. High levels of serum FSH were associated with rapid gonadal growth in the fish exposed to the stimulatory long-short photoperiod. In contrast, the fish exposed to the ambient photoperiod showed gonadal steroid production, formation of vitellogenin, and secondary oocyte growth without any detectable increase in serum FSH levels. The possible roles and interactions of sGnRH, gonadotropins, and steroids with respect to normal and artificially stimulated ovarian maturation are discussed.
Animals↗
Stripping the long saphenous vein reduces the rate of reoperation for recurrent varicose veins: five-year results of a randomized trial.
OBJECTIVE: The purpose of this study was to investigate the possible long-term clinical advantages of stripping the long saphenous vein during routine primary varicose vein surgery. METHODS: The study was designed as a 5-year, clinical and duplex scan follow-up examination of a group of patients who were randomized to stripping of the long saphenous vein during varicose vein surgery versus saphenofemoral ligation alone. The study was conducted in the vascular unit of a district general hospital. One hundred patients (133 legs) with uncomplicated primary long saphenous varicose veins originally were randomized. After invitation 5 years later, 78 patients (110 legs) underwent clinical review and duplex scan imaging. RESULTS: Sixty-five patients remained pleased with the results of their surgery (35 of 39 stripped vs 30 of 39 ligated; P = .13). Reoperation, either done or awaited, for recurrent long saphenous veins was necessary for three of 52 of the legs that underwent stripping versus 12 of 58 ligated legs. The relative risk was 0.28, with a 95% confidence interval of 0.13 to 0.59 (P = .02). Neovascularization at the saphenofemoral junction was responsible for 10 of 12 recurrent veins that underwent reoperation and also was the cause of recurrent saphenofemoral incompetence in 12 of 52 stripped veins versus 30 of 58 ligated legs. The relative risk was 0.45, with a 95% confidence interval of 0.26 to 0.78 (P = .002). CONCLUSION: Stripping reduced the risk of reoperation by two thirds after 5 years and should be routine for primary long saphenous varicose veins.
Humans↗
Poor outcome in patients aged over 80 with limb-threatening ischaemia.
The aim of this study was to determine the outcome in a consecutive series of patients over 80 years of age with limb-threatening ischaemia. The authors performed a retrospective case-note review of the treatment and outcome in 108 patients with 131 episodes of leg ischaemia, who presented to a vascular unit between 1992-1996 inclusively. Some 73 (56%) episodes of leg ischaemia occurred in patients suitable for active treatment (limb salvage 75%, amputation 4% and death 21%). Results were inferior in patients not actively treated (limb salvage 19%, amputation 50% and death 31%). Elderly patients not selected for active treatment have a very poor outcome and are seldom mentioned in publications. In future, clinical reports should include actively treated and rejected patients to avoid selection bias. Research should focus on the selection process and alternative therapies.
Aged↗
Peripheral thrombolysis for acute-onset claudication. Thrombolysis Study Group.
BACKGROUND: The aim of this study was to determine the outcome of patients who presented with sudden onset of incapacitating claudication of less than 2 weeks' duration and who were treated with peripheral arterial thrombolysis. METHODS: The database of the Thrombolysis Study Group was searched retrospectively for patients who received thrombolysis for acute-onset claudication. Some 108 patients (65 men, median age 69 (range 29-94) years) were treated with intra-arterial tissue plasminogen activator at 14 hospitals. The median duration of symptoms was 72 h (range from 2 h to 2 weeks). There were 52 graft and 56 native vessel arterial occlusions. RESULTS: The immediate outcome of thrombolysis for native vessel arterial occlusion was thrombus clearance in 50 patients (89 per cent) and failed lysis in six (11 per cent). Thirty-six patients (64 per cent) had a secondary radiological or surgical procedure carried out after lysis. After 30 days four patients (7 per cent) had a major amputation, eight (14 per cent) had died, 38 (68 per cent) were symptom free and seven (12 per cent) continued to have claudication. Three patients (5 per cent) suffered a major haemorrhage. The immediate outcome of thrombolysis for graft occlusion was thrombus clearance in 48 patients (92 per cent) and failed lysis in four (8 per cent); 27 patients (52 per cent) had a secondary procedure. After 30 days four patients (8 per cent) had a major amputation, seven (13 per cent) had died, 32 (62 per cent) were symptom free and nine (17 per cent) had persistent claudication. Three patients (6 per cent) suffered a major haemorrhage. CONCLUSION: Patients who presented with acute onset of incapacitating claudication had an outcome similar to that after thrombolysis for critical ischaemia. It is recommended that patients who present in this way should be observed and treated with thrombolysis only if they progress to critical ischaemia. Presented to the Association of Surgeons of Great Britain and Ireland, Edinburgh, UK, May 1998, and published in abstract form as Br J Surg 1998; 85(Suppl 1): 24
Adult↗
Vascular surgical society of great britain and ireland: first year of a fast-track carotid duplex service
BACKGROUND: The risk of a major stroke after a transient ischaemic attack (TIA) is highest in the first 3 months after the onset of symptoms. Urgent endarterectomy in appropriate cases is recommended through a fast-track one-stop assessment clinic. METHODS: Local general practitioners (GPs) were informed that a duplex scan would be guaranteed within 14 days of referral of any patient who had a recent clearly documented TIA or amaurosis fugax. Referral letters were faxed and the scan was authorized by a consultant surgeon. Those with significant disease were seen in the clinic in preparation for operation. Non-significant results were conveyed by post to the GPs with no further action. RESULTS: In the first 12 months of the service, 90 scans were performed through the fast track. In the same interval 490 non-fast-track scans were done after request by a physician (38 per cent), geriatrician (24 per cent), neurologist (14 per cent), vascular surgeon (11 per cent), ophthalmologist (8 per cent) or others (4 per cent). Thirteen (14 per cent) of 90 patients in the fast-track group had carotid endarterectomy, with a median period between referral and operation of 30 (range 20-45) days and median time between onset of symptoms and surgery of 7 (range 4-58) weeks. Endarterectomy was carried out in 12 (2 per cent) of 490 patients in the routine group with a median duration between referral and operation of 127 (range 64-184) days. CONCLUSION: A fast-track service can significantly reduce the time between referral and operation, and increase the number of endarterectomies. Urgent and appropriate referral from the GPs is vital for the service to work efficiently.
Journal Article↗