Central and peripheral mediation of human force sensation following eccentric or concentric contractions

Fatigue was induced in the triceps brachii of the experimental arm by a regimen of either eccentric or concentric muscle actions. Estimates of force were assessed using a contralateral limb-matching procedure, in which target force levels (25 %, 50 % or 75 % of maximum) were defined by the unfatigued control arm. Maximum isometric force-generating capacity was reduced by 31 % immediately following eccentric contractions, and remained depressed at 24 (25 %) and 48 h (13 %) post-exercise. A less marked reduction (8.3 %) was observed immediately following concentric contractions. Those participants who performed prior eccentric contractions, consistently (at all force levels), and persistently (throughout the recovery period), overestimated the level of force applied by the experimental arm. In other words, they believed that they were generating more force than they actually achieved. When the forces applied by the experimental and the control arm, were each expressed as a proportion of the maximum force that could be attained at that time, the estimates matched extremely closely. This outcome is that which would be expected if the estimates of force were based on a sense of effort. Following eccentric exercise, the amplitude of the EMG activity recorded from the experimental arm was substantially greater than that recorded from the control arm. Cortically evoked potentials recorded from the triceps brachii (and extensor carpi radialis) of the experimental arm were also substantially larger than those elicited prior to exercise. The sense of effort was evidently not based upon a corollary of the central motor command. Rather, the relationship between the sense of effort and the motor command appears to have been altered as a result of the fatiguing eccentric contractions. It is proposed that the sense of effort is associated with activity in neural centres upstream of the motor cortex.

Characterization of calcium-activated chloride channels in patches excised from the dendritic knob of mammalian olfactory receptor neurons

We investigated the properties of calcium-activated chloride channels in inside-out membrane patches from the dendritic knobs of acutely dissociated rat olfactory receptor neurons. Patches typically contained large calcium-activated currents, with total conductances in the range 30-75 nS. The dose response curve for calcium exhibited an EC50 of about 26 mu M. In symmetrical NaCl solutions, the current-voltage relationship reversed at 0 mV and was linear between -80 and +70 mV. When the intracellular NaCl concentration was progressively reduced from 150 to 25 mM, the reversal potential changed in a manner consistent with a chloride-selective conductance. Indeed, modeling these data with the Goldman-Hodgkin-Katz equation revealed a P-Na/P-Cl of 0.034. The halide permeability sequence was P-Cl > P-F > P-I > P-Br indicating that permeation through the channel was dominated by ion binding sites with a high field strength. The channels were also permeable to the large organic anions, SCN-, acetate(-), and gluconate(-), with the permeability sequence P-Cl > P-SCN > gluconaie. Significant permeation to gluconate ions suggested that the channel pore had a minimum diameter of at least 5.8 Angstrom.

Evidence for persistent dysfunction of wild-type aldosterone synthase gene in glucocorticoid-treated familial hyperaldosteronism type I

Background In familial hyperaldosteronism type I (FH-I), glucocorticoid treatment suppresses adrenocorticotrophic hormone-regulated hybrid gene expression and corrects hyperaldosteronism. Objective To determine whether the wild-type aldosterone synthase genes, thereby released from chronic suppression, are capable of functioning normally. Methods We compared mid-morning levels of plasma potassium, plasma aldosterone, plasma renin activity (PRA) and aldosterone : PRA ratios, measured with patients in an upright position, and responsiveness of aldosterone levels to infusion of angiotensin II (AII), for 11 patients with FH-I before and during long-term (0.8-14.3 years) treatment with 0.25-0.75 mg/day dexamethasone or 2.5-10 mg/day prednisolone. Results During glucocorticoid treatment, hypertension was corrected in all. Potassium levels, which had been low (< 3.5 mmol/l) in two patients before treatment, were normal in all during treatment (mean 4.0 +/- 0.1 mmol/l, range 3.5-4.6). Aldosterone levels during treatment [13.2 +/- 2.1 ng/100 ml (mean +/- SEM)] were lower than those before treatment (20.1 +/- 2.5 ng/100 ml, P < 0.05). PRA levels, which had been suppressed before treatment (0.5 +/- 0.2 ng/ml per h), were unsuppressed during treatment (5.1 +/- 1.5 ng/ml per h, P < 0.01) and elevated (> 4 ng/ml per h) in six patients. Aldosterone : PRA ratios, which had been elevated (> 30) before treatment (101.1 +/- 25.9), were much lower during treatment (4.1 +/- 1.0, P < 0.005) and below normal (< 5) in eight patients. Surprisingly, aldosterone level, which had not been responsive (< 50% rise) to infusion of AII for all 11 patients before treatment, remained unresponsive for 10 during treatment. Conclusions Apparently regardless of duration of glucocorticoid treatment in FH-I, aldosterone level remains poorly responsive to AII, with a higher than normal PRA and a low aldosterone : PRA ratio. This is consistent with there being a persistent defect in functioning of wild-type aldosterone synthase gene. (C) Rapid Science Publishers ISSN 0263-6352.

The influence of joint position on the dynamics of perception-action coupling

Six right-handed subjects performed rhythmic flexion and extension movements of the index finger in time with an auditory metronome. On each block of trials, the wrist of the response hand was placed in a extended, neutral or flexed position. In the flex-on-the-beat condition, subjects were instructed to coordinate maximum excursion in the direction of finger flexion with each beat of the metronome. In the extend-on-the-beat condition, subjects were instructed to coordinate maximum excursion in the direction of finger extension with each beat of the metronome. The frequency of the metronome was increased from 2.00 Hz to 3.75 Hz in 8 steps (8 s epochs) of 0.25 Hz. During trials prepared in the extend-on-the-beat pattern, all subjects exhibited transitions to either a flex-on-the-beat pattern or to phase wandering as the frequency of pacing was increased. The time at which these transitions occurred was reliably influenced by the position of the wrist. Four subjects exhibited qualitative departures from the flex-on-the-beat pattern at pacing frequencies that were greater than those at which the extend-on-the-beat pattern could be maintained. The lime at which these departures occurred was not influenced by the position of the wrist. These results are discussed with reference to the constraints imposed on the coordination dynamics by the intrinsic properties of the neuromuscular-skeletal system.

Effect of metabolic inhibitors on cyclosporine pharmacokinetics using a population approach

Drugs known to inhibit the metabolism of cyclosporine are administered concomitantly to those who undergo cardiothoracic transplantation. The aim of this study was to examine in quantitative terms the relationship between cyclosporine oral dose rate and the trough concentration (Css(trough)) at steady state in patients who undergo cardiothoracic transplantation and are administered cyclosporine alone or in combination with drugs known to inhibit its metabolism. Dose and whole blood cyclosporine Css(tough) observations measured using the enzyme-multiplied immunoassay technique (EMIT) (396 observations) or the TDx assay (435 observations) were collected as part of routine blood concentration monitoring from 182 patients who underwent cardiothoracic transplantation. Data were analyzed using a linear mixed-effects modeling approach to examine the effect of metabolic inhibitors on dose-rate-Css(trough) ratio. The mean (and 95% confidence interval) dose-rate-Css(trough) ratio for cyclosporine generated from concentrations measured using EMIT was 94 (82.5-105.5) Lh(-1) for patients administered cyclosporine alone, 66.7 (58.1-75.3) Lh(-1) for patients administered concomitant diltiazem, 47.9 (15.4 -80.4) Lh(-1) for patients administered concomitant itraconazole, 21.7 (14.8-28.5) Lh(-1) for patients administered concomitant ketoconazole, and 14.9 (11.8-18.1) Lh(-1) for patients concomitantly administered diltiazem and ketoconazole. For patients administered concomitant cyclosporine, ketoconazole, and diltiazem, the dosage of cyclosporine, if it is administered alone, should be 20% to achieve the same blood concentrations. This will allow safer drug concentration targeting of cyclosporine after cardiothoracic transplantation.

Heart rate, blood lactate and kinematic data of elite colts (under-19) rugby union players during competition

Physiological and kinematic data were collected from elite under-19 rugby union players to provide a greater understanding of the physical demands of rugby union. Heart rate, blood lactate and time-motion analysis data were collected from 24 players (mean +/- s((x) over bar): body mass 88.7 +/- 9.9 kg, height 185 +/- 7 cm, age 18.4 +/- 0.5 years) during six competitive premiership fixtures. Six players were chosen at random from each of four groups: props and locks, back row forwards, inside backs, outside backs. Heart rate records were classified based on percent time spent in four zones (>95%, 85-95%, 75-84%, <75% HRmax). Blood lactate concentration was measured periodically throughout each match, with movements being classified as standing, walking, jogging, cruising, sprinting, utility, rucking/mauling and scrummaging. The heart rate data indicated that props and locks (58.4%) and back row forwards (56.2%) spent significantly more time in high exertion (85-95% HRmax) than inside backs (40.5%) and outside backs (33.9%) (P < 0.001). Inside backs (36.5%) and outside backs (38.5%) spent significantly more time in moderate exertion (75-84% HRmax) than props and locks (22.6%) and back row forwards (19.8%) (P < 0.05). Outside backs (20.1%) spent significantly more time in low exertion (< 75% HRmax) than props and locks (5.8%) and back row forwards (5.6%) (P < 0.05). Mean blood lactate concentration did not differ significantly between groups (range: 4.67 mmol.l(-1) for outside backs to 7.22 mmol.l(-1) for back row forwards; P < 0.05). The motion analysis data indicated that outside backs (5750 m) covered a significantly greater total distance than either props and locks or back row forwards (4400 and 4080 m, respectively; P < 0.05). Inside backs and outside backs covered significantly greater distances walking (1740 and 1780 m, respectively; P < 0.001), in utility movements (417 and 475 m, respectively; P < 0.001) and sprinting (208 and 340 m, respectively; P < 0.001) than either props and locks or back row forwards (walking: 1000 and 991 m; utility movements: 106 and 154 m; sprinting: 72 and 94 m, respectively). Outside backs covered a significantly greater distance sprinting than inside backs (208 and 340 m, respectively; P < 0.001). Forwards maintained a higher level of exertion than backs, due to more constant motion and a large involvement in static high-intensity activities. A mean blood lactate concentration of 4.8-7.2 mmol.l(-1) indicated a need for 'lactate tolerance' training to improve hydrogen ion buffering and facilitate removal following high-intensity efforts. Furthermore, the large distances (4.2-5.6 km) covered during, and intermittent nature of, match-play indicated a need for sound aerobic conditioning in all groups (particularly backs) to minimize fatigue and facilitate recovery between high-intensity efforts.

Long-term risk of first recurrent stroke in the Perth Community Stroke Study

Background and Purpose-Few community-based studies have examined the long-term risk of recurrent stroke after an acute first-ever stroke. This study aimed to determine the absolute and relative risks of a first recurrent stroke over the first 5 years after a first-ever stroke and the predictors of such recurrence in a population-based series of people with first-ever stroke in Perth, Western Australia. Methods-Between February 1989 and August 1990, all people with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. Results-Three hundred seventy patients with a first-ever stroke were registered, of whom 351 survived >2 days. Data were available for 98% of the cohort at 5 years, by which time 199 patients (58%) had died and 52 (15%) had experienced a recurrent stroke, 12 (23%) of which were fatal within 28 days. The 5-year cumulative risk of first recurrent stroke was 22.5% (95% confidence limits [CL], 16.8%, 28.1%). The risk of recurrent stroke was greatest in the first 6 months after stroke, at 8.8% (95% CL, 5.4%, 12.1%). After adjustment for age and sex, the prognostic factors for recurrent stroke were advanced, but not extreme, age (75 to 84 years) (hazard ratio [HR], 2.6; 95% CL, 1.1, 6.2), hemorrhagic index stroke (HR, 2.1; 95% CL, 0.98, 4.4), and diabetes mellitus (HR, 2.1; 95% CL, 0.95, 4.4). Conclusions-Approximately 1 in 6 survivors (15%) of a first-ever stroke experience a recurrent stroke over the next 5 years, of which 25% are fatal within 28 days. The pathological subtype of the recurrent stroke is the same as that of the index stroke in 88% of cases. The predictors of first recurrent stroke in this study were advanced age, hemorrhagic index stroke, and diabetes mellitus, but numbers of recurrent events were modest. Because the risk of recurrent stroke is highest (8.8%) in the first 6 months after stroke, strategies for secondary prevention should be initiated as soon as possible after the index event.

Leaking urine in Australian women: Prevalence and associated conditions

The paper aims to (1) assess the prevalence of leaking urine and to (2) explore associations between leaking urine and a variety of other symptoms, conditions, surgical procedures and life events in three large cohorts of Australian women, who are participants in the Australian Longitudinal Study on Women's Health. Young women aged 18-23 (N = 14,000), mid-age women, 45-50 (N 13,738) and older women, 70-75 (N = 12,417), were recruited randomly from the national HIC/Medicare database. Leaking urine was reported by approximately one in eight young women [estimated prevalence 12.8% (95% CI: 12.2-13.3)] and one in three mid-age women [36.1% (CI: 35.2-37.0)] and older women [35.0% (CI: 34.1-35.9)]. Leaking urine was significantly associated with parity, conditions which increase the pressure on the pelvic floor such as constipation and obesity, past gynecological surgery and conditions which can impact on bladder control. The study showed that fewer than half the women had sought help for the problem and that younger women were less likely to be satisfied with the help available for this problem. Strategies for continence promotion, including opportunistic raising of the issue at the time of cervical screening and pregnancy care are suggested, so that the health and social outcomes of untreated chronic incontinence in women might be improved.

Leaking urine: Prevalence and associated factors in Australian women

The Women's Health Australia project provided the opportunity to examine the prevalence of leaking urine and associated variables in three large cohorts of Australian women 18-23 years of age (young N = 14,761), 45-50 (mid-age N = 14,070), and 70-75 (older N = 12,893). The proportion of women reporting leaking urine was 12.8% (95% CI: 12.2-13.3), 36.1% (35.2-37.0), and 35% (34.1-35.9) in each of the three cohorts, respectively. Logistic regression analysis showed significant associations between leaking urine and parity in the young and mid-age women, and between leaking urine and constipation, other bowel symptoms, body mass index, and urine that burns or stings in all three groups. in the mid-age and older cohorts, women who reported having both hysterectomy and prolapse repair, or prolapse repair alone, were also more likely to report leaking urine. Lower scores on the physical and mental component summary scores of the medical outcomes survey short form (36 items) questionnaire suggest lower quality of life among women who report leaking urine, compared with those who do not. (C) 1999 Wiley-Liss,Inc.

Wall material properties of yeast cells. Part II. Analysis

In the preceding paper (Part I) force-deformation data were measured with the compression experiment in conjunction with the initial radial stretch ratio and the initial wall-thickness to cell-radius ratio for baker's yeast (Saccharomyces cerevisiae). In this paper, these data have been analysed with the mechanical model of Smith et al. (Smith, Moxham & Middelberg (1998) Chemical Engineering Science, 53, 3913-3922) with the wall constitutive behaviour defined a priori as incompressible and linear-elastic. This analysis determined the mean Young's modulus ((E) over bar), mean maximum von Mises stress-at-failure (<(sigma)over bar>(VM,f)) and mean maximum von Mises strain-at failure (<(epsilon)over bar>(VM,f)) to be (E) over bar = 150 +/- 15 MPa, <(sigma)over bar>(VM,f) = 70 +/- 4 MPa and <(epsilon)over bar>(VM,f) = 0.75 +/- 0.08, respectively. The mean Young's modulus was not dependent (P greater than or equal to 0.05) on external osmotic pressure (0-0.8 MPa) nor compression rate (1.03-7.68 mu m/s) suggesting the incompressible linear-elastic relationship is representative of the actual cell-wall constitutive behaviour. Hydraulic conductivities were also determined and were comparable to other similar cell types (0-2.5 mu m/MPa s). The hydraulic conductivity distribution was not dependent on external osmotic pressure (0-0.8 MPa) nor compression rate (1.03-7.68 mu m/s) suggesting inclusion of cell-wall permeability in the mechanical model is justified. <(epsilon)over bar>(VM,f) was independent of cell diameter and to a first-approximation unaffected (P greater than or equal to 0.01) by external osmotic pressure and compression rate, thus providing a reasonable failure criterion. This criterion states that the cell-wall material will break when the strain exceeds <(epsilon)over bar>(VM,f) = 0.75 +/- 0.08. Variability in overall cell strength during compression was shown to be primarily due to biological variability in the maximum von Mises strain-at-failure. These data represent the first estimates of cell-wall material properties for yeast and the first fundamental analysis of cell-compression data. They are essential for describing cell-disruption at the fundamental level of fluid-cell interactions in general bioprocesses. They also provide valuable new measurements for yeast-cell physiologists. (C) 2000 Elsevier Science Ltd. All rights reserved.

Effect of increased lung expansion on lung growth and development near midgestation in fetal sheep

Obstruction of the fetal trachea is a potent stimulus for fetal lung growth and may have therapeutic potential in human fetuses with lung hypoplasia. However, the effects of increased lung expansion on lung development near midgestation, which is the preferred timing for fetal intervention, have not been well studied. Our aim was to determine the effects of increased lung expansion on lung development at 75-90 d of gestation in fetal sheep. In three groups of fetuses (n = 4 for each), the trachea was occluded for either 10 [10-d tracheal occlusion (TO) group] or 15 d (15-d TO group) or left intact (control fetuses). TO for both 10 and 15 d caused fetal hydrops, resulting in significantly increased fetal body weights. Both periods of TO significantly increased total lung DNA contents from 99.8 +/- 10.1 to 246.0 +/- 5.3 and 246.9 +/- 48.7 mg in 10- and 15-d TO fetuses, respectively. TO for 10 and 15 d also increased airspace diameter, although the percentage of lung occupied by airspace was not increased in 10-d TO fetuses due to large increases in interairway distances; this resulted from a large increase in mesenchymal tissue. The interairway distances at 15 d of TO were reduced compared with the 10-d value but were still similar to 30% larger than control values. We conclude that TO at

Analysis of proximal femur DXA scans in growing children: Comparisons of different protocols for cross-sectional 8-month and 7-year longitudinal data

Dual-energy X-ray absorptiometry (DXA) is a widely used method for measuring bone mineral in the growing skeleton. Because scan analysis in children offers a number of challenges, we compared DXA results using six analysis methods at the total proximal femur (PF) and five methods at the femoral neck (FN), In total we assessed 50 scans (25 boys, 25 girls) from two separate studies for cross-sectional differences in bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) and for percentage change over the short term (8 months) and long term (7 years). At the proximal femur for the short-term longitudinal analysis, there was an approximate 3.5% greater change in bone area and BMC when the global region of interest (ROI) was allowed to increase in size between years as compared with when the global ROI was held constant. Trend analysis showed a significant (p < 0.05) difference between scan analysis methods for bone area and BMC across 7 years. At the femoral neck, cross-sectional analysis using a narrower (from default) ROI, without change in location, resulted in a 12.9 and 12.6% smaller bone area and BMC, respectively (both p < 0.001), Changes in FN area and BMC over 8 months were significantly greater (2.3 %, p < 0.05) using a narrower FN rather than the default ROI, Similarly, the 7-year longitudinal data revealed that differences between scan analysis methods were greatest when the narrower FN ROI was maintained across all years (p < 0.001), For aBMD there were no significant differences in group means between analysis methods at either the PF or FN, Our findings show the need to standardize the analysis of proximal femur DXA scans in growing children.

Ni-II and Zn-II complexes of the hexadentate macrocyclic ligand cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetra- decane-6,13-diamine

The title pendent-arm macrocyclic hexaamine ligand binds stereospecifically in a hexadentate manner, and we report here its isomorphous Ni-II and Zn-II complexes (both as perchlorate salts), namely (cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine-kappa(6)N)nickel(II) diperchlorate, [Ni(C12H30N6)](ClO4)(2), and (cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine-kappa(6)N)zinc(II) diperchlorate, [Zn(C-12 H30N6)](ClO4)(2). Distortion of the N-M-N valence angles from their ideal octahedral values becomes more pronounced with increasing metal-ion size and the present results are compared with other structures of this ligand.

Feed intake and liveweight responses to nitrogen and/or protein supplements by steers of Bos taurus, Bos indicus and Bos taurus x Bos indicus breed types offered a low quality grass hay

Thirty steers were used in two pen experiments (Expts 1 and 2). and 27 of these in a third (Expt 3), to quantify their responses of hay intake, rumen ammonia nitrogen (RAN) concentrations, and liveweight to inputs of rumen soluble nitrogen (urea) and rumen undegradable protein (formaldehyde-treated casein; F-casein) when added to a basal diet of low quality hays. The hays were made From unimproved native pastures typical of those grazed by cattle in the subtropics of Australia and contained 7.8 g N/kg dry matter (DM) with coefficient of organic matter digestibility of 0.503 in Expts 1 and 2, and 5.2 g N/kg DM with a digestibility range from 0.385 to 0.448 in Expt 3. The steers (15 months old) were either Brahman (B), Hereford (H) or the F-1 Brahman x Hereford (BH) cross. Steers were offered supplementary minerals with the hays in each experiment. In Expt 1 (35 days) urea was sprayed on part of the hay, allowing for daily urea intakes (g/steer) of either 0, 5, 11, 16 or 26. In Expt 2 (42 days), F-casein was offered daily (g/steer) at either 0, 75, 150, 225 or 300 and in Expt 3 (56 days) discrete offerings were made of soluble casein (225 g/day), of urea (18 g/day) + F-casein (225 g/day) or of nil. There were significant linear effects of urea intake upon hay intake and liveweight change of steers. However, B steers had smaller increases in intake and liveweight change than did H steers, and B steers did not have a linear increase in RAN concentrations with increasing urea intake as did H and SH steers. In Expt 2 there were significant linear effects of F-casein supplements on hay intake and liveweight change of steers and a significant improvement in their feed conversion ratio (i.e. DM intake:liveweight change). The B steers did not differ from H and BH steers in liveweight change but had significantly lower hay intakes and non-significantly smaller increases in RAN with increasing F-casein intake. In Expt 3, hay intake of the steers increased with soluble casein (by 16.8 %) and with urea + F-casein (24.5 %). Only steers given urea + F-casein had a high RAN concentration (94 mg/l) and a high liveweight gain. The B steers had a liveweight loss and a lower hay intake than H or BH steers in Expt 3 but a higher RAN concentration. These studies have indicated the importance of the form and quantity of additional N required by cattle of differing breed types to optimize their feed intake and liveweight gain when offered low-N, low-digestible hays.