Quality assessment of online patient information on upper gastrointestinal endoscopy using the modified Ensuring Quality Information for Patients tool.

INTRODUCTION: Websites and online resources are increasingly becoming patients' main source of healthcare information. It is paramount that high quality information is available online to enhance patient education and improve clinical outcomes. Upper gastrointestinal (UGI) endoscopy is the gold standard investigation for UGI symptoms and yet little is known regarding the quality of patient orientated websites. The aim of this study was to assess the quality of online patient information on UGI endoscopy using the modified Ensuring Quality Information for Patients (EQIP) tool. METHODS: Ten search terms were employed to conduct a systematic review. for each term, the top 100 websites identified via a Google search were assessed using the modified EQIP tool. High scoring websites underwent further analysis. Websites intended for professional use by clinicians as well as those containing video or marketing content were excluded. FINDINGS: A total of 378 websites were eligible for analysis. The median modified EQIP score for UGI endoscopy was 18/36 (interquartile range: 14-21). The median EQIP scores for the content, identification and structure domains were 8/18, 1/6 and 9/12 respectively. Higher modified EQIP scores were obtained for websites produced by government departments and National Health Service hospitals (p=0.007). Complication rates were documented in only a fifth (20.4%) of websites. High scoring websites were significantly more likely to provide balanced information on risks and benefits (94.6% vs 34.4%, p<0.001). CONCLUSIONS: There is an immediate need to improve the quality of online patient information regarding UGI endoscopy. The currently available resources provide minimal information on the risks associated with the procedure, potentially hindering patients' ability to make informed healthcare decisions.

Cortico-cerebellar connectivity underlying motor control in chronic post-stroke individuals.

The robust, reciprocal anatomical connections between the cerebellum and contralateral sensorimotor cerebral hemisphere underscores the strong physiological interdependence between these two regions in relation to human behavior. Previous studies have shown that damage to sensorimotor cortex can result in a lasting reduction of cerebellar metabolism, the magnitude of which has been linked to poor rehabilitative outcomes. A better understanding of movement-related cerebellar physiology as well as cortico-cerebellar coherence (CCC) in the chronic, post-stroke state may be key to developing novel neuromodulatory techniques that promote upper limb motor rehabilitation. As a part of the first in-human phase-I trial investigating the effects of deep brain stimulation of the cerebellar dentate nucleus (DN) on chronic, post-stroke motor rehabilitation, we collected invasive recordings from DN and scalp EEG in subjects (both sexes) with middle cerebral artery stroke during a visuo-motor tracking task. We investigated the excitability of ipsilesional cortex, DN and the their interaction as a function of motor impairment and performance. Our results indicate that 1) event-related oscillations in the ipsilesional cortex and DN were significantly correlated at movement onset in the low-ß band, with moderately and severely impaired subjects showing desynchronization and synchronization, respectively. 2) Significant CCC was observed during isometric 'hold' period in the low-ß band, which was critical for maintaining task accuracy. Our findings support a strong coupling between ipsilesional cortex and DN in the low-ß band during motor control across all impairment levels which encourages the exploitation of the cerebello-thalamo-cortical pathway as a neuromodulation target to promote rehabilitation.Significance Statement:Cerebral infarct due to stroke can lead to lasting reduction in cerebellar metabolism resulting in poor rehabilitative outcomes. Thorough investigation of the cerebellar electrophysiology as well as cortico-cerebellar connectivity in humans that could provide key insights to facilitate development of novel neuromodulatory technologies, has been lacking. As a part of the first in-human phase-I trial investigating deep brain stimulation of the cerebellar dentate nucleus (DN) for chronic, post-stroke motor rehabilitation, we collected invasive recordings from DN and scalp EEG while stroke patients performed a motor task. Our data indicate strong coupling between ipsilesional sensorimotor cortex and DN in the low-ß band across all impairment levels encouraging the exploration of electrical stimulation of the DN.

Reliability of TMS metrics in patients with chronic incomplete spinal cord injury.

STUDY DESIGN: Test-retest reliability analysis in individuals with chronic incomplete spinal cord injury (iSCI). OBJECTIVES: The purpose of this study was to examine the reliability of neurophysiological metrics acquired with transcranial magnetic stimulation (TMS) in individuals with chronic incomplete tetraplegia. SETTING: Cleveland Clinic Foundation, Cleveland, Ohio, USA. METHODS: TMS metrics of corticospinal excitability, output, inhibition and motor map distribution were collected in muscles with a higher MRC grade and muscles with a lower MRC grade on the more affected side of the body. Metrics denoting upper limb function were also collected. All metrics were collected at two sessions separated by a minimum of two weeks. Reliability between sessions was determined using Spearman's correlation coefficients and concordance correlation coefficients (CCCs). RESULTS: We found that TMS metrics that were acquired in higher MRC grade muscles were approximately two times more reliable than those collected in lower MRC grade muscles. TMS metrics of motor map output, however, demonstrated poor reliability regardless of muscle choice (P=0.34; CCC=0.51). Correlation analysis indicated that patients with more baseline impairment and/or those in a more chronic phase of iSCI demonstrated greater variability of metrics. CONCLUSION: In iSCI, reliability of TMS metrics varies depending on the muscle grade of the tested muscle. Variability is also influenced by factors such as baseline motor function and time post SCI. Future studies that use TMS metrics in longitudinal study designs to understand functional recovery should be cautious as choice of muscle and clinical characteristics can influence reliability.

Models to Tailor Brain Stimulation Therapies in Stroke.

A great challenge facing stroke rehabilitation is the lack of information on how to derive targeted therapies. As such, techniques once considered promising, such as brain stimulation, have demonstrated mixed efficacy across heterogeneous samples in clinical studies. Here, we explain reasons, citing its one-type-suits-all approach as the primary cause of variable efficacy. We present evidence supporting the role of alternate substrates, which can be targeted instead in patients with greater damage and deficit. Building on this groundwork, this review will also discuss different frameworks on how to tailor brain stimulation therapies. To the best of our knowledge, our report is the first instance that enumerates and compares across theoretical models from upper limb recovery and conditions like aphasia and depression. Here, we explain how different models capture heterogeneity across patients and how they can be used to predict which patients would best respond to what treatments to develop targeted, individualized brain stimulation therapies. Our intent is to weigh pros and cons of testing each type of model so brain stimulation is successfully tailored to maximize upper limb recovery in stroke.

Adequacy of diagnostic tests and surgical management of symptomatic invasive lobular carcinoma of the breast.

INTRODUCTION: Invasive lobular carcinoma (ILC) presents diagnostic and therapeutic challenges as it produces subtle radiological changes. It has been suggested that it is not suitable for breast conserving surgery (BCS). The aim of this study was to ascertain the diagnostic adequacy of modern mammography and ultrasonography in the context of a fast track symptomatic diagnostic clinic in the UK. It also sought to compare the mastectomy, re-excision and BCS rates for ILC with those for invasive ductal carcinoma (IDC). METHODS: A retrospective analysis of prospectively collected data was carried out on all new symptomatic cancers presenting to the one-stop diagnostic clinic of a single breast unit between 1998 and 2007. RESULTS: Compared with IDC, ILC was significantly larger at presentation (46mm vs 25mm), needed re-excision after BCS more often (38.8% vs 22.3%) and required mastectomy more frequently (58.8% vs 40.8%). Although mammography performs poorly in diagnosing ILC compared with IDC, when combined with ultrasonography, sensitivity of the combined imaging was not significantly different between these two histological types. CONCLUSIONS: Provided ultrasonography is performed, standard radiological imaging is adequate for initial diagnosis of symptomatically presenting ILC but some additional preoperative workup should clearly be employed to reduce the higher number of reoperations for this histological type.

Sentinel node biopsy can replace four-node-sampling in staging early breast cancer.

AIM: Four-node axillary sampling for breast cancer is an established method of staging the axilla in the United Kingdom. We report the sensitivity of sentinel node (SN) biopsy and compare it with that of four-node sampling. METHODS: SN identification was attempted in 234 consecutive patients with unifocal breast cancers up to 25 mm in diameter on pre-operative ultrasound. A combination of isotope-labelled nanocolloid and patent blue dye techniques were used and SN were identified in 221 (94.5%). All patients underwent back-up four-node sampling and those with positive sentinel nodes on frozen section (FS) underwent immediate full axillary clearance. RESULTS: Among those patients who had SN successfully identified, an average of 1.38 SN were identified per patient. Histological examination of the SN alone would have identified all node-positive patients that the four-node sample identified. CONCLUSION: In patients who have SN identified, four-node axillary sampling does not provide any additional information.

Core biopsy versus FNAC for palpable breast cancers. Is image guidance necessary?

The aim of this study was to assess the efficacy of free-hand percutaneous core biopsy (FHCB) and to determine the role of fine needle aspiration cytology (FNAC) as diagnostic tools for palpable radiologically-suspicious breast lumps. This retrospective study was based on reviewing the clinical records of all patients diagnosed as having breast cancer between January 1999 and December 2000 and patients who had benign lesions, but suspicious breast imaging at triple assessment. Absolute sensitivity of FHCB for diagnosing cancer in palpable lesions was 98.7% compared with 51.3% for FNAC. The difference in the sensitivity of FHCB and FNAC was statistically significant (P<0.005, Wilcoxon matched pair test). Since 94.8% of radiologically-suspicious lumps were shown to be cancers, we advocate FHCB for all patients presenting with radiologically suspicious palpable lumps to our breast clinic. We also conclude that the sensitivity of FHCB for the diagnosis of malignancy in palpable radiologically-suspicious breast lesions is so high that image-guidance is unnecessary.

Peripheral chemoreceptor contributions to sympathetic and cardiovascular responses during hypercapnia.

We tested the hypothesis that integrated sympathetic and cardiovascular reflexes are modulated by systemic CO2 differently in hypoxia than in hyperoxia (n = 7). Subjects performed a CO2 rebreathe protocol that equilibrates CO2 partial pressures between arterial and venous blood and that elevates end tidal CO2 (PET(CO2)) from approximately 40 to approximately 58 mmHg. This test was repeated under conditions where end tidal oxygen levels were clamped at 50 (hypoxia) or 200 (hyperoxia) mmHg. Heart rate (HR; EKG), stroke volume (SV; Doppler ultrasound), blood pressure (MAP; finger plethysmograph), and muscle sympathetic nerve activity (MSNA) were measured continuously during the two protocols. MAP at 40 mmHg PET(CO2) (i.e., the first minute of the rebreathe) was greater during hypoxia versus hyperoxia (P < 0.05). However, the increase in MAP during the rebreathe (P < 0.05) was similar in hypoxia (16 +/- 3 mmHg) and hyperoxia (17 +/- 2 mmHg PET(CO2)). The increase in cardiac output (Q) at 55 mmHg PET(CO2) was greater in hypoxia (2.61 +/- 0.7 L/min) versus hyperoxia (1.09 +/- 0.44 L/min) (P < 0.05). In both conditions the increase in Q was due to elevations in both HR and SV (P < 0.05). Systemic vascular conductance (SVC) increased to similar absolute levels in both conditions but rose earlier during hypoxia (> 50 mmHg PET(CO2)) than hyperoxia (> 55 mmHg). MSNA increased earlier during hypoxic hypercapnia (> 45 mmHg) compared with hyperoxic hypercapnia (> 55 mmHg). Thus, in these conscious humans, the dose-response effect of PET(CO2) on the integrated cardiovascular responses was shifted to the left during hypoxic hypercapnia. The combined data indicate that peripheral chemoreceptors exert important influence over cardiovascular reflex responses to hypercapnia.

Analysis of patients treated with living pig tissue for evidence of infection by porcine endogenous retroviruses.

The use of pigs as a source of cells and organs for transplantation has the potential to reduce the current chronic shortage of organs for the treatment of many end-stage diseases. The risk of transmission of infectious agents across the species barrier (zoonoses) has to be assessed. Many such agents can be eliminated from the pig herd. However, porcine endogenous retroviruses, which are carried within the pig genome, are not easily eliminated. They can infect primary and immortalized human cells in vitro, but to date no evidence for in vivo infection has been found in retrospective studies of humans exposed to viable porcine cells. Small-scale clinical trials using porcine cells for the treatment of Parkinson's and Huntington's disease are currently in progress. The prospective monitoring of these patients in conjunction with further research into the biology of this virus will help address safety issues.

Determinants of oxygen uptake kinetics in older humans following single-limb endurance exercise training.

We hypothesised that the observed acceleration in the kinetics of exercise on-transient oxygen uptake (VO2) of five older humans (77 +/- 7 years (mean +/- S.D.) following 9 weeks of single-leg endurance exercise training was due to adaptations at the level of the muscle cell. Prior to, and following training, subjects performed constant-load single-limb knee extension exercise. Following training VO2 kinetics (phase 2, tau) were accelerated in the trained leg (week 0, 92 +/- 44 s; week 9, 48 +/- 22 s) and unchanged in the untrained leg (week 0, 104 +/- 43 s; week 9, 126 +/- 35 s). The kinetics of mean blood velocity in the femoral artery were faster than the kinetics of VO2, but were unchanged in both the trained (week 0, 19 +/- 10 s; week 9, 26 +/- 11 s) and untrained leg (week 0, 20 +/- 18 s; week 9, 18 +/- 10 s). Maximal citrate synthase activity, measured from biopsies of the vastus lateralis muscle, increased (P < 0.05) in the trained leg (week 0, 6.7 +/- 2.0 micromol x (g wet wt)(-1) x min(-1); week 9, 11.4 +/- 3.6 micromol x (g wet wt)(-1) x min(-1)) but was unchanged in the untrained leg (week 0, 5.9 +/- 0.5 micromol x (g wet wt)(-1) x min(-1); week 9, 7.9 +/- 1.9 micromol x (g wet wt)(-1) x min(-1)). These data suggest that the acceleration of VO2 kinetics was due to an improved rate of O2 utilisation by the muscle, but was not a result of increased O2 delivery.

A comparison of modelling techniques used to characterise oxygen uptake kinetics during the on-transient of exercise.

We compared estimates for the phase 2 time constant (tau) of oxygen uptake (VO2) during moderate- and heavy-intensity exercise, and the slow component of VO2 during heavy-intensity exercise using previously published exponential models. Estimates for tau and the slow component were different (P < 0.05) among models. For moderate-intensity exercise, a two-component exponential model, or a mono-exponential model fitted from 20 s to 3 min were best. For heavy-intensity exercise, a three-component model fitted throughout the entire 6 min bout of exercise, or a two-component model fitted from 20 s were best. When the time delays for the two- and three-component models were equal the best statistical fit was obtained; however, this model produced an inappropriately low DeltaVO2/DeltaWR (WR, work rate) for the projected phase 2 steady state, and the estimate of phase 2 tau was shortened compared with other models. The slow component was quantified as the difference between VO2 at end-exercise (6 min) and at 3 min (DeltaVO2 (6-3 min)); 259 ml x min(-1)), and also using the phase 3 amplitude terms (truncated to end-exercise) from exponential fits (409-833 ml x min(-1)). Onset of the slow component was identified by the phase 3 time delay parameter as being of delayed onset approximately 2 min (vs. arbitrary 3 min). Using this delay DeltaVO2 (6-2 min) was approximately 400 ml x min(-1). Use of valid consistent methods to estimate tau and the slow component in exercise are needed to advance physiological understanding.

Lung function in older humans: the contribution of body composition, physical activity and smoking.

An allometric model was used to determine the important factors related to the decline in forced expiratory volume (FEV1.0) across ages 55-86 years in independently living men and women. Measurements were available from a randomized sample of 181 men and 203 women residing in London, Ontario, Canada. The effects of height, age, sex, adiposity, fat free mass (FFM), grip strength and physical activity (PA) on FEV1.0 were assessed using an allometric model to test the hypothesis that sex differences in lung function would be due in part to sex-related differences in the aforementioned variables and would therefore be eliminated by our analysis. The following model was linearized and parameters were identified using standard multiple regression: FEV1.0 = height(beta1) x FFM(beta2) x grip strength(beta3) x PA(beta4) x exp(beta0 + beta5age + beta6sex + beta7smoking + beta8%body fat) x epsilon. Results indicate that the amount of FFM and heavy intensity physical activity participated in by the elderly may be more important in influencing forced expiratory function than previously recognized. In addition, results from this study have confirmed the importance of age and height in the prediction of FEV1.0 and demonstrated a negative effect of smoking on lung function. Individuals with a greater FFM and physical activity level tended to be associated with an above average lung function performance. The cross-sectional rate of decline in FEV1.0 determined from our model was approximately 12% per decade.

Dynamic ventilatory response to acute isocapnic hypoxia in septuagenarians.

This study compared the ventilatory response to 20 min of acute isocapnic hypoxia (end-tidal P(O(2)), 50 mmHg) using the technique of dynamic end-tidal forcing in young (Y) and old (O) men. Two groups of non-smoking male subjects (mean +/- s.d. age: Y, 29.8 +/- 6.9 years; O, 73.4 +/- 2.8 years) with similar body size, normal age-predicted spirometry, and normal moderate levels of physical activity were studied. Compared with baseline ventilation in euoxia (10.79 +/- 1.99 and 11.88 +/- 0.91 l min-1) both groups responded to the abrupt onset of isocapnic hypoxia with peak ventilatory responses of 22.58 +/- 2.60 and 24.56 +/- 2.54 l min-1 for Y and O, respectively (not significant, n.s.). Both groups demonstrated a significant increment in neuromuscular drive (i.e. tidal volume (V(T))/inspiratory time (T(I)); 0.46 +/- 0.06 to 0.91 +/- 0.15 and 0.48 +/- 0.06 to 0.91 +/- 0.12 l s-1 for Y and O, respectively) with a small (but also significant) change in central timing (T(I)/total ventilation time (T(tot)); 0.38 +/- 0.02 to 0.41 +/- 0.02 and 0.42 +/- 0.02 to 0.45 +/- 0.02 for Y and O, respectively). Oxygen sensitivity was assessed using Weil's equation, and gave a hyperbolic factor (A) of 282 +/- 75 and 317 +/- 72, and using the linear equation: change in expiratory minute volume (DeltaV.(E))/change in arterial O(2) saturation (DeltaS(a,O(2))) which gave -1.17 +/- 0.57 and -1.17 +/- 0.42 l min-1 %-1 (n.s.) for Y and O, respectively. After 20 min of sustained isocapnic hypoxia, ventilation declined to 14.29 +/- 1.92 and 16.85 +/- 2.34 l min-1 for Y and O, respectively (n.s.). The acute response to hypoxia was characterised by similar time constants (16.0 +/- 5.4 and 18.5 +/- 6.7 s) and time delays (4.8 +/- 2.1 and 4.6 +/- 1.9 s) for Y and O, respectively. Thus, the dynamic ventilatory response to acute isocapnic hypoxia is maintained into the eighth decade in a group of habitually active elderly men. Experimental Physiology (2001) 86.1, 117-126.

A self-paced step test to predict aerobic fitness in older adults in the primary care clinic.

OBJECTIVES: To study the potential usefulness of a submaximal self-paced step test as a prediction of maximal aerobic capacity (VO2max) in older adults in the primary care setting. DESIGN: Data were collected during a prospective randomized study of an exercise program. SETTING: Four university family medical clinics in London, Ontario, Canada. PARTICIPANTS: A random sample of 240 healthy older (> or =65) men (n = 118) and women (n = 122) from four family medical clinics underwent self-paced step testing in the clinic with a family physician (n = 16), and step testing and a maximal exercise treadmill test with measurement of respired gases in an exercise laboratory. Testing was done in random order (clinic/laboratory) separated by 2 weeks and then repeated at 52 weeks, following introduction of an exercise program. Relationships between outcome variables were examined by Pearson correlation coefficients while prediction of VO2max was examined using multivariate regression analysis. Cross-validation with 30 age-matched hypertensive and 40 age-matched post-hip arthroplasty patients was used to test the accuracy of the predictive models. MEASUREMENTS: Measured VO2max, predicted VO2max, step test time, step test heart rate, body mass index (BMI), and O2 pulse. RESULTS: Two hundred women (n = 108) and men (n = 92) completed both the initial and 52-week assessments. Stepping time, heart rate, age, BMI, and O2 pulse were strongly associated with VO2max for both a normal and a fast step pace and were chosen to develop the predictive model. Normal step-pace correlation with VO2max (ml/kg/min) was no different (female 0.93: male 0.91) from fast pace (0.95:0.90) with no difference between clinic and laboratory measurement at baseline or 52 weeks. Cross-validation showed no significant difference from the main group using the predictive model. CONCLUSIONS: The self-paced step test is a safe and simple clinical instrument that strongly and reliably predicts VO2max, is sensitive to change, and is generalizable in the family practice setting among community-dwelling older adults differing in fitness and health status.

Monitoring xenotransplant recipients for infection by PERV.

OBJECTIVES: Concerns have been raised over the possibility of transmission of porcine endogenous retrovirus (PERV) to porcine xenograft recipients. METHODS: To help assess this risk, diagnostic assays capable of detection of an active, latent or cleared PERV infection, and the presence of pig cell microchimerism have been developed by a number of groups. Retrospective studies of patients exposed to living pig tissues have been performed using these assays to look for evidence of cross species transmission. RESULTS: To date no evidence of PERV infection has been found in studies of humans exposed to pig tissues, despite evidence of long lived microchimerism. CONCLUSIONS: These data suggest that PERV infection has not occurred in a clinical setting. However, as infection has been seen in a small animal model further investigation of the risk from PERV is warranted.

Left ventricular diastolic filling and cardiovascular functional capacity in older men.

We investigated anaerobic threshold (< theta(L)) gas exchange kinetics and maximal oxygen uptake (VO2,max) among older men with reduced left ventricular end-diastolic filling (LVDF). Ten men (mean age, 73 years) with LVDF impairment and low fitness, but without other cardiovascular dysfunction were studied. Treatments compared to control included: 5 days, high intensity exercise training protocol; 5 days, calcium channel blockade (240 mg verapamil); 21 days, detraining/washout; and 5 days, combined treatments. Results indicated no changes in resting left ventricular systolic function with any treatment. Significant resting diastolic function changes included increased early:late flow velocity (control, 0.87; training, 1.28; verapamil, 1.32), and a decreased isovolumic relaxation time (control, 0.10 s; training, 0.08 s; verapamil, 0.08 s). The combined treatments were not additive. Sub-threshold oxygen uptake kinetics (tauVO2, s) were significantly faster following either training or verapamil (tauVO2,control, 62+/-12; tauVO2,training, 44+/-9; tauVO2,verapamil, 48+/-10) and combined treatments (tauVO2, 41+/- 8). V O2,max (ml kg(-1) min(-1)) was significantly increased (control, 21.8+/-2.2; training, 27.3+/-2.2; verapamil, 25.2+/-3.4; combined treatments, 26.9+/-2.3). Increasing ventricular preload with either exercise training or calcium channel blockade was coincident with faster tauVO2 and increased VO2,max.

The off-transient pulmonary oxygen uptake (VO(2)) kinetics following attainment of a particular VO(2) during heavy-intensity exercise in humans.

The oxygen uptake response to moderate-intensity exercise (i.e. < anaerobic threshold (an)) has been characterised with a gain (i.e. response amplitude per increment of work rate) and time constant that do not vary appreciably at different work rates or between the on- and off-transients. Above an, the response becomes more complex with an early component that typically projects to a value that has a gain similar to that of the < an response, but which is supplemented by the addition of a delayed slow kinetic component. We therefore established a constant target VO2 (VO21) for each subject such that with different imposed work rates the contribution to VO21 from the slow phase varied over a wide range. Work rates were chosen so that VO21 was attained at 2-24 min. Five subjects (aged 21-58 years) cycled at four to five different work rates. VO2 was measured breath-by-breath, at VO21 the work rate was abruptly reduced and the subject recovered by cycling unloaded for 15 min. Unlike the on-transient, for which the slow component shows a long delay, the off-transient was best fitted as two simultaneous exponential components. The slower off-transient component had a small amplitude and long time constant, but did not differ significantly among the various tests. The off-transient kinetics for VO2 therefore was independent of the magnitude of the contribution to the slow phase from the on-transient kinetics.

Carbonic anhydrase inhibition delays plasma lactate appearance with no effect on ventilatory threshold.

The effect of carbonic anhydrase (CA) inhibition with acetazolamide (Acz, 10 mg/kg body wt iv) on exercise performance and the ventilatory (VET) and lactate (LaT) thresholds was studied in seven men during ramp exercise (25 W/min) to exhaustion. Breath-by-breath measurements of gas exchange were obtained. Arterialized venous blood was sampled from a dorsal hand vein and analyzed for plasma pH, PCO(2), and lactate concentration ([La(-)](pl)). VET [expressed as O(2) uptake (VO(2)), ml/min] was determined using the V-slope method. LaT (expressed as VO(2), ml/min) was determined from the work rate (WR) at which [La(-)](pl) increased 1.0 mM above rest levels. Peak WR was higher in control (Con) than in Acz sutdies [339 +/- 14 vs. 315 +/- 14 (SE) W]. Submaximal exercise VO(2) was similar in Acz and Con; the lower VO(2) at exhaustion in Acz than in Con (3.824 +/- 0. 150 vs. 4.283 +/- 0.148 l/min) was appropriate for the lower WR. CO(2) output (VCO(2)) was lower in Acz than in Con at exercise intensities >/=125 W and at exhaustion (4.375 +/- 0.158 vs. 5.235 +/- 0.148 l/min). [La(-)](pl) was lower in Acz than in Con during submaximal exercise >/=150 W and at exhaustion (7.5 +/- 1.1 vs. 11.5 +/- 1.1 mmol/l). VET was similar in Acz and Con (2.483 +/- 0.086 and 2.362 +/- 0.110 l/min, respectively), whereas the LaT occurred at a higher VO(2) in Acz than in Con (2.738 +/- 0.223 vs. 2.190 +/- 0.235 l/min). CA inhibition with Acz is associated with impaired elimination of CO(2) during the non-steady-state condition of ramp exercise. The similarity in VET in Con and Acz suggests that La(-) production is similar between conditions but La(-) appearance in plasma is reduced and/or La(-) uptake by other tissues is enhanced after the Acz treatment.

Changes in chemoreflex characteristics following acute carbonic anhydrase inhibition in humans at rest.

The effect of carbonic anhydrase (CA) inhibition with acetazolamide (ACZ, 10 mg kg(-1) I.V.) on the peripheral and central chemosensitivity and breathing pattern was investigated in four women and three men aged 25 +/- 3 years using a modified version of Read's rebreathing technique. Subjects were exposed to dynamic increases in CO2 in hypoxic and hyperoxic backgrounds during control conditions and following acute CA inhibition. All manoeuvres were repeated twice and averaged for data analysis. The central chemoreflex sensitivities, estimated from the slopes of the ventilatory response to CO2 during hyperoxic rebreathing, increased following acute CA inhibition (control vs. ACZ treatment: 1.87 +/- 0.66 vs. 4.07 +/- 1.03 l x min(-1) (mmHg CO2)(-1), P < 0.05). The increased slope was reflected by an increase in the rate of rise of tidal volume and breathing frequency. Furthermore with ACZ, there was a left-ward shift of the ventilation vs. end-tidal PCO2 curve during hyperoxic hypercapnia but not hypoxic hypercapnia. The peripheral chemoreflex sensitivity was isolated by subtracting the hyperoxic slope (central only) from the hypoxic slope (central and peripheral). Following ACZ administration, the peripheral chemosensitivity was blunted (control vs. ACZ treatment: 3.66 +/- 0.92 vs. 1.33 +/- 0.46 l x min(-1) (mmHg CO2)(-1), P < 0.05). In conclusion, acute CA inhibition enhanced the central chemosensitivity to CO2 but diminished the peripheral chemosensitivity.

Modelling the influence of fat-free mass and physical activity on the decline in maximal oxygen uptake with age in older humans.

The purpose of this study was to use an allometric model (maximal oxygen uptake (VO2,max) = FFMbeta1 x PAbeta2 x exp(beta0 + beta3 age + beta4 sex) x epsilon) to determine the influence of fat-free mass (FFM), physical activity (PA), sex and age on VO2,max in older men (n = 152) and women (n = 146) aged 55-86 years. VO2,max was measured during a fatigue-limited treadmill test, FFM was determined from skinfold thickness and physical activity by the Minnesota Leisure Time Physical Activity questionnaire. The model was linearised by taking the natural logarithm of VO2,max, FFM and physical activity. Variables were selected using multiple linear regression (P < 0.05). The sex variable was not significant (P = 0.062). The model explained 72.1% of the variance in VO2,max. Significant individual coefficients were incorporated into the model yielding the following expression: VO2,max = FFM0.971 x PA0.026 x exp(-2.48-0.015age). Therefore, FFM and physical activity were significant factors contributing to the changes in VO2,max with age. In addition, controlling for FFM and physical activity abolished sex differences in VO2,max. The rate of decline in VO2,max (after accounting for FFM and physical activity) with age, was approximately 15% per decade.