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A measles epidemic threshold in a highly vaccinated population.

BACKGROUND: Mass vaccination against measles has successfully lowered the incidence of the disease and has changed the epidemic pattern from a roughly biennial cycle to an irregular sequence of outbreaks. A possible explanation for this sequence of outbreaks is that the vaccinated population is protected by solid herd immunity. If so, we would expect to see the fraction of susceptible individuals remaining below an epidemic threshold. An alternative explanation is the occurrence of occasional localised lapses in herd immunity that allow for major outbreaks in areas with a low vaccine coverage. In that case, we would expect the fraction of susceptible individuals to exceed an epidemic threshold before outbreaks occur. These two explanations for the irregular sequence of measles outbreaks can be tested against observations of both the fraction of susceptible individuals and infection attack rates. METHODS AND FINDINGS: We have estimated both the fraction of susceptible individuals at the start of each epidemic year and the infection attack rates for each epidemic year in the Netherlands over a 28-y period. During this period the vaccine coverage averaged 93%, and there was no sustained measles transmission. Several measles outbreaks occurred in communities with low vaccine coverage, and these ended without intervention. We show that there is a clear threshold value for the fraction of susceptible individuals, below which only minor outbreaks occurred, and above which both minor and major outbreaks occurred. A precise, quantitative relationship exists between the fraction of susceptible individuals in excess of this threshold and the infection attack rate during the major outbreaks. CONCLUSION: In populations with a high but heterogeneous vaccine coverage, measles transmission can be interrupted without establishing solid herd immunity. When infection is reintroduced, a major outbreak can occur in the communities with low vaccine coverage. During such a major outbreak, each additional susceptible individual in excess of the threshold is associated with almost two additional infections. This quantitative relationship offers potential for anticipating both the likelihood and size of future major outbreaks when measles transmission has been interrupted.

Disease Outbreaks↗

Distortion-product otoacoustic emissions in Mongolian gerbils with resistance to noise-induced hearing loss.

Distortion-product otoacoustic emissions (DPOAEs) and the endocochlear potential (EP) were recorded in adult Mongolian gerbils exposed to noise for either 1 or 12 days. The exposure was an octave band of noise centered at 4 kHz at 80 dB SPL with a duty cycle of 6 h on, 18 h off. A previous study showed that a single such exposure causes 20-50 dB of temporary threshold shift (TTS) in the neural response at 4-8 kHz, but that the TTS is reduced to less than 10 dB following 12 daily exposures [Boettcher, J. Acoust. Soc. Am. 94, 3207-3214 (1993)]. This reduction in TTS is commonly referred to as resistance to noise-induced hearing loss (NIHL). To further analyze whether resistance to NIHL is caused by changes in the outer hair cell (OHC) system or the lateral wall system (or both), DPOAEs and EPs were measured in the exposed ears. The amplitudes of DPOAEs were significantly reduced in the frequency region from 4 to 10 kHz in subjects exposed to noise for 1 day, but were relatively normal in subjects exposed for 12 days. DPOAE amplitudes from frequency regions below the spectrum of the exposure were similar across the exposure and control groups except at the low-frequency edge of the noise where DPOAE amplitudes were consistently higher than normal in the exposed animals. The EP values in both exposure groups were not reduced from normal, unexposed levels. Thus there was no causal relationship between changes in the EP and the reduction of the DPOAE amplitudes. These data suggest that the development of resistance to noise is related to an initial depression of OHC activity followed by a recovery of activity to a stable level, despite an ongoing exposure.

Animals↗

Effect of inspiratory resistive loading on control of ventilation during progressive exercise.

Eight healthy volunteers performed gradational tests to exhaustion on a mechanically braked cycle ergometer, with and without the addition of an inspiratory resistive load. Mean slopes for linear ventilatory responses during loaded and unloaded exercise [change in minute ventilation per change in CO2 output (delta VE/delta VCO2)] measured below the anaerobic threshold were 24.1 +/- 1.3 (SE) = l/l of CO2 and 26.2 +/- 1.0 l/l of CO2, respectively (P greater than 0.10). During loaded exercise, decrements in VE, tidal volume, respiratory frequency, arterial O2 saturation, and increases in end-tidal CO2 tension were observed only when work loads exceeded 65% of the unloaded maximum. There was a significant correlation between the resting ventilatory response to hypercapnia delta VE/delta PCO2 and the ventilatory response to VCO2 during exercise (delta VE/delta VCO2; r = 0.88; P less than 0.05). The maximal inspiratory pressure generated during loading correlated with CO2 sensitivity at rest (r = 0.91; P less than 0.05) and with exercise ventilation (delta VE/delta VCO2; r = 0.83; P less than 0.05). Although resistive loading did not alter O2 uptake (VO2) or heart rate (HR) as a function of work load, maximal VO2, HR, and exercise tolerance were decreased to 90% of control values. We conclude that a modest inspiratory resistive load reduces maximum exercise capacity and that CO2 responsiveness may play a role in the control of breathing during exercise when airway resistance is artificially increased.

Adult↗

Effects of fenoterol on inspiratory effort sensation and fatigue during inspiratory threshold loading.

We studied the effects of a single dose of fenoterol on the relationship between inspiratory effort sensation (IES) and inspiratory muscle fatigue induced by inspiratory threshold loading in healthy subjects. The magnitude of the threshold was 60% of maximal static inspiratory mouth pressure (PI,mmax) at functional residual capacity, and the duty cycle was 0.5. Subjects continued the threshold loaded breathing until the target mouth pressure could no longer be maintained (endurance time). The intensity of the IES was scored with a modified Borg scale. Either fenoterol (5 mg) or a placebo was given orally 2 h before loading in a randomized double-blind crossover protocol. The endurance time with fenoterol (34.4 +/- 8.6 min) was longer than that with the placebo (22.2 +/- 7.1 min; P < 0.05). The ratio of high- to low-frequency power of the diaphragmatic electromyogram (EMGdi) decreased during loading; the decrease was less with fenoterol (P < 0.05). The EMGdi also decreased with loading; the decrease was greater on fenoterol treatment (P < 0.01). The PI,mmax and maximal transdiaphragmatic pressure (Pdi) were similarly decreased after loading on either treatment. The intensity of the IES rose with time during loading in both groups but was lower with fenoterol than with the placebo (P < 0.05). The ratio of Pdi to integrated activity of the EMGdi increased with fenoterol (P < 0.05). Fenoterol treatment increased both superimposed Pdi twitch and Pdi twitch of relaxed diaphragm and decreased the value of (1-superimposed Pdi twitch/Pdi twitch of relaxed diaphragm). Thus we conclude that in normal subjects fenoterol reduces diaphragmatic fatigue and decreases the motor command to the diaphragm, resulting in a decrease in IES during inspiratory threshold loading and a prolongation of endurance.

Adult↗

Comparison of 12 reference genes for normalization of gene expression levels in Epstein-Barr virus-transformed lymphoblastoid cell lines and fibroblasts.

BACKGROUND: Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCLs) and skin fibroblasts are often used to establish or confirm the effect of mutations on gene expression levels. Relative quantification of gene expression is usually achieved by comparison of the expression level of a gene of interest with that of a suitable reference gene. Hence, the choice of reference gene is critical in all experiments that require normalization of expression data. METHODS: For normalization of gene expression levels in both EBV-LCLs and skin fibroblasts, we compared six common reference genes (ACTB, GAPDH, GUSB, HPRT1, PPIB, and TFRC) with six alternative reference genes (CLK2, COPS5, PCYT1A, RAD51L1, RNF10, and RNF111). The alternative genes were selected on the basis of their stability in expression levels in EBV-LCLs according to microarray data. The 12 genes were ranked according to stability in expression levels based on the standard deviation (SD) of the cycle threshold (Ct), geNorm, NormFinder, and the SD of the comparative cycle threshold (DeltaDeltaCt). In addition, we predicted the validity of an observed difference in expression level of a gene of interest between two samples when a specific reference gene is used. RESULTS AND CONCLUSIONS: In our dataset, GUSB and CLK2 were the best choices as reference genes for EBV-LCLs and fibroblasts, respectively. For almost all reference genes, expression level differences of <2-fold between two samples were most likely not significant (p > 0.05). GAPDH for EBV-LCLs and GAPDH and HPRT1 for fibroblasts should not be used for normalization in these cell lines because of their variability in expression levels.

B-Lymphocytes↗

Tour de France versus Vuelta a España: which is harder?

PURPOSE: To compare the total exercise loads (intensity x volume) of the Vuelta a España and Tour de France during the last year. METHODS: Seven professional road cyclists (28 +/- 1 yr; [OV0312]O(2max): 74.6 +/- 2.2 mL.kg-1.min-1) who participated in both Tour and Vuelta during the years 1997, 1999, 2000, or 2001 were collected as subjects. They wore a heart rate (HR) telemeter during each stage of the two races, and exercise intensity was divided into three phases according to the reference HR values obtained during a previous ramp cycle-ergometer test: phase I ( RCP). Total volume and intensity were integrated as a single variable. The score for volume x intensity in each phase was computed by multiplying the accumulated duration in this phase by a multiplier for this particular phase. The total score for Tour and Vuelta was obtained by summating the results of the three phases. RESULTS: The total loads (volume x intensity) did not significantly differ between the two races (P > 0.05), despite a significantly longer total exercise time of the Tour (P < 0.05) (5552 +/- 176 vs 5086 +/- 290 min). CONCLUSION: The physiological loads imposed on cyclists' bodies do not differ between the Tour and Vuelta, despite the longer duration of daily stages in the former race.

Adult↗

A reappraisal of vector control strategies for babesiosis.

This review suggests that we are on the threshold of a new epoch in the control of ticks and the diseases transmitted by them. Ecological studies of parasitic and non-parasitic stages of the tick life cycle have shown how strategic dipping can lead to effective control of Boophilus ticks. However, this approach can lead to drastic reduction in tick populations which may favour the development of enzootic instability. On the other hand, mathematical models and field studies indicate that we can eradicate babesiosis without eradicating the tick vector. As no well-established vaccine exists for babesiosis or its vectors, it is important to anticipate the possible effects of low or fluctuating populations of ticks caused by strategic control programmes. Under these conditions, it is probable that babesiosis will disappear before the tick vector does. Prudent use of tick bionomic data from several centres of field research, as well as models to analyse these data, should accelerate the latter process. Epidemiological models should be included in the analysis of babesiosis in areas that run the risk of converting from stable zones to unstable zones due to strategic dipping. These observations and projections underscore the value of integration of traditional and modern techniques in the control of babesiosis and other vector-borne diseases.

Analysis of Variance↗

Different effects of two regeneration regimens on immunological parameters in cyclists.

PURPOSE: To investigate the effect of 4-d active regeneration of different duration on immunological parameters after 2 wk of intensive training. METHODS: In a cross-over design 11 male cyclists conducted 13 d of intensive training followed by 4 d of low-intensity cycling for either 1 or 3 h each day (sequence randomized). Before the intensive training (test 1), between training and regeneration (test 2), and after the regeneration period (test 3), subjects were tested in the lab: venous blood sampling (immunological parameters; flow cytometry) and incremental exercise stage test on acycle ergometer. RESULTS: Average values of lymphocytes and natural killer (NK) cells decreased significantly from test 1 to test 2 and were influenced differently by 1- and 3-h cycling (P = 0.018 and 0.039, respectively); 1-h cycling restored values from test 1, whereas 3 h led to a further decrease in lymphocyte and NK cell concentrations. This pattern was resembled by the courses of maximal heart rate and maximal blood lactate concentration during incremental cycling exercise. In leukocytes, tests 2 and 3 differed significantly from test 1 (P = 0.048 and 0.031, respectively), but there was no significant effect of the regeneration duration (P = 039). Neither the concentration of neutrophils nor the neutrophil oxidative burst was significantly influenced by the training period or by one of the regeneration phases. CONCLUSIONS: The present results indicate that low-intensity regenerative training sessions in cyclists should preferably be conducted for shorter durations than 3 h. It was demonstrated that 4-d cycling of 1 h each day reversed ergometric and immunological changes indicative of fatigue after 2 wk of intensive training.

Adult↗

Detection of Campylobacter jejuni in dairy farm environmental samples using SYBR Green real-time polymerase chain reaction.

The aim of this study was to evaluate a SYBR Green based real-time PCR assay using well-characterized primers to detect Campylobacter jejuni in naturally contaminated dairy farm environmental samples. Specificity of the assay was determined with 62 C. jejuni strains and 120 non-C. jejuni strains. Peak melting temperature obtained with melting curves specific for C. jejuni was 77.5 degrees C. Standard curves were constructed using mean threshold cycle (C(T)) and various concentrations of C. jejuni ranging from 10(0) to 10(8) colony forming units (CFU)/mL, which resulted in a linear relationship between C(T) and log input DNA. Correlation coefficients of standard curves based on pure culture of C. jejuni in broth and spiked cells in lagoon water were R(2) = 0.995 (slope = 3.21) and R(2) = 0.988 (slope = 3.22), respectively, and sensitivity limits were <10 and >10(3) CFU/mL, respectively. After 24-h enrichment, total C. jejuni counts of all samples spiked with 10(0) CFU/mL reached >10(5) CFU/mL, and the detection limit was improved from >10(3) CFU/mL to <10 CFU/mL of inoculum in broth. Eighty-two dairy farm environmental samples, including fecal slurry, feed/silage, lagoon water, drinking water, bulk tank milk, farm soil, and bedding material, were analyzed. The real-time PCR assay detected C. jejuni in 25 (30.4%) of 82 samples, with 17 (68%) of these samples being culture positive for C. jejuni. All samples that were positive by standard culture methods were also positive by the real-time PCR method. Mean C( T ) values of 48-h enriched cultures for 17 PCR-positive/culture-positive samples and eight PCR-positive/culture-negative samples were 21.4 +/- 3.6, and 34.6 +/- 1.5 (p < 0.0001), respectively. C( T ) values for negative samples were >38.0. These results indicate that the SYBR Green real-time PCR assay provides a specific, reproducible, and simple method for detecting C. jejuni in dairy farm environmental samples.

Animals↗

Retraining of a competitive master athlete following traumatic injury: a case study.

PURPOSE: The purpose of this study was to examine the physiological effects of detraining and retraining in a female master cyclist (age, 49.5 yr; wt, 54 kg) following a surgically-treated clavicular fracture complicated by brachial plexus impingement. METHODS: Variables associated with cycling performance, including VO2max, lactate threshold (LT), power output at a blood lactate concentration of 4 mM (LT(4 mM)), peak power output (PPO), muscular resistance to fatigue measured by a timed ride to exhaustion at 110% of peak power output (PPO110), and body composition (hydrostatic weight) were assessed 2 d before the injury when the subject was at the peak of her competitive season, and at days 0, 14, 28, 42, and 77 of the retraining period. Retraining gradually increased from 3 h x wk(-1) to 9-10 h x wk(-1) with an increase in intensity from approximately 70 to 95+% of HRmax. RESULTS: Detraining resulted in a 25.7% decrease in VO2max and a 16.7% and 18.9% decrease in LT and LT(4 mM), respectively, while peak power output and PPO110 declined 18.2% and 16.6%, respectively. Body fat percent increased 2.1 percentage points, while fat-free mass decreased nearly 2 kg. After 2 wk of retraining, all variables except the LT and LT(4 mM) had improved considerably; however, VO2max was still 14.8% lower and PPO and PPO110 were 12.7% and 5.7% lower than preinjury values. By the 11th week of retraining, all variables had essentially returned to their preinjury values. CONCLUSION: These data demonstrate a pattern of retraining in which aerobic power steadily improved over 6 wk, while measures of lactate threshold did not change until the fourth week of retraining when the intensity of training was markedly increased. Additional data are needed to determine whether this pattern of retraining would be consistent in other master athletes.

Bicycling↗

Metabolic and cardioventilatory responses during a graded exercise test before and 24 h after a triathlon.

Previous studies have reported respiratory, cardiac and muscle changes at rest in triathletes 24 h after completion of the event. To examine the effects of these changes on metabolic and cardioventilatory variables during exercise, eight male triathletes of mean age 21.1 (SD 2.5) years (range 17-26 years) performed an incremental cycle exercise test (IET) before (pre) and the day after (post) an official classic triathlon (1.5-km swimming, 40-km cycling and 10-km running). The IET was performed using an electromagnetic cycle ergometer. Ventilatory data were collected every minute using a breath-by-breath automated system and included minute ventilation (V(E)), oxygen uptake (VO2), carbon dioxide production (VCO2), respiratory exchange ratio, ventilatory equivalent for oxygen (V(E)/VO2) and for carbon dioxide (V(E)/VCO2), breathing frequency and tidal volume. Heart rate (HR) was monitored using an electrocardiogram. The oxygen pulse was calculated as VO2/HR. Arterialized blood was collected every 2 min throughout IET and the recovery period, and lactate concentration was measured using an enzymatic method. Maximal oxygen uptake (VO2max) was determined using conventional criteria. Ventilatory threshold (VT) was determined using the V-slope method formulated earlier. Cardioventilatory variables were studied during the test, at the point when the subject felt exhausted and during recovery. Results indicated no significant differences (P > 0.05) in VO2max [62.6 (SD 5.9) vs 64.6 (SD 4.8) ml x kg(-1) x min(-1)], VT [2368 (SD 258) vs 2477 (SD 352) ml x min(-1)] and time courses of VO2 between the pre- versus post-triathlon sessions. In contrast, the time courses of HR and blood lactate concentration reached significantly higher values (P < 0.05) in the pre-triathlon session. We concluded that these triathletes when tested 24 h after a classic triathlon displayed their pre-event aerobic exercise capacity, bud did not recover pretriathlon time courses in HR or blood lactate concentration.

Adolescent↗

Application of quantitative real-time reverse transcription-PCR in assessing drug efficacy against the intracellular pathogen Cryptosporidium parvum in vitro.

We report here on a quantitative real-time reverse transcription-PCR (qRT-PCR) assay for assessing drug efficacy against the intracellular pathogen Cryptosporidium parvum. The qRT-PCR assay detects 18S rRNA transcripts from both parasites, that is, the cycle threshold for 18S rRNA from parasites (C(T)([P18S])) and host cells (C(T)([H18S])), and evaluates the relative expression between parasite and host rRNA levels (i.e., deltaC(T) = C(T)([P18S]) - C(T)([H18S])) to minimize experimental and operational errors. The choice of qRT-PCR over quantitative PCR (qPCR) in this study is based on the observations that (i) the relationship between the logarithm of infected parasites (log[P]) and the normalized relative level of rRNA (deltadeltaC(T)) is linear, with a fourfold dynamic range, by qRT-PCR but sigmoidal (nonlinear) by qPCR; and (ii) the level of RNA represents that of live parasites better than that of DNA, because the decay of RNA (99% in approximately 3 h) in dead parasites is faster than that of DNA (99% in approximately 24 to 48 h) under in vitro conditions. The reliability of the qRT-PCR method was validated by testing the efficacies of nitazoxanide and paromomycin on the development of two strains of C. parvum (IOWA and KSU-1) in HCT-8 cells in vitro. Both compounds displayed dose-dependent inhibitions. The observed MIC50 values for nitazoxanide and paromomycin were 0.30 to 0.45 micro/ml and 89.7 to 119.0 microg/ml, respectively, comparable to the values reported previously. Using the qRT-PCR assay, we have also observed that pyrazole could inhibit C. parvum development in vitro (MIC50 = 15.8 mM), suggesting that the recently discovered Cryptosporidium alcohol dehydrogenases may be explored as new drug targets.

Animals↗

Early predictors of substantial weight gain in bipolar patients treated with olanzapine.

To determine predictors of substantial weight gain (SWG) during treatment of bipolar disorder with olanzapine, data were pooled from 4 long-term randomized, multicenter studies in patients with bipolar mania or mixed mania (N = 948 at initiation of olanzapine). SWG was defined as gaining 5 kg or 7% of initial weight in 30 +/- 2 weeks. Logistic regression estimated odds ratios associated with early weight gain and baseline risk factors for predicting SWG. A classification system to identify patients at risk for SWG was constructed by recursive data partitioning. Baseline characteristics significantly associated with SWG included younger age, nonwhite ethnicity, lower body mass index (BMI), nonrapid cycling, and psychotic features. Weight gain of 2 or more kg in the first 3 weeks of therapy predicted SWG by 30 weeks (sensitivity = 57%; specificity = 71%). A classification system with thresholds for early weight gain, baseline BMI, and ethnicity further improved SWG predictability (sensitivity = 79%; specificity = 70%). In conclusion, patients with bipolar disorder who gained 2 to 3 kg during the first 3 weeks of treatment with olanzapine, SWG was predicted after 30 weeks of treatment. Patients with less pronounced early weight gain might still be at risk for later SWG if they have close to normal BMI (< or =27 kg/m) at treatment initiation.

Adult↗

Involvement of retinal and extraretinal photoreceptors in the mediation of nocturnal locomotor activity rhythms in the catfish, Silurus asotus.

Retinal and extraretinal photoreceptor organs involved in synchronization of nocturnal locomotor activity under 12-h light:12-h dark cycle (LD12:12) were investigated in catfish, Silurus asotus. Catfishes studied were: (1) intact; (2) pinealectomized; (3) blinded; (4) blinded and pinealectomized; and (5) blinded, pinealectomized, with the brain region covered with aluminum foil. When the light intensity was reduced during the light phase of the LD cycle, the threshold for 24-h rhythmicity was determined, by observing the synchronization to the given LD cycle with periodograms. Intact catfish showed almost the same threshold intensity (in the order of 10(-3) microW/cm2) as that of either blinded or pinealectomized animals. This suggests that information is combined through both organs and is related to the 24-h rhythm of locomotor activity at lower intensities. However, the animal without the eye and pineal organ could display 24-h rhythmicity at intensities higher by approximately 3 log units than those of the animals described above. This indicates the existence of extraretinal and non-pineal photoreceptors (ENPs), and the involvement of at least three types of photoreceptor in mediating nocturnal locomotor activity rhythms at higher intensities. One of the possible ENPs was assumed to be in the brain region.

Animals↗

Determination of accumulated O2 deficit in exhaustive short-duration exercise.

Usually, an initial step in determining accumulated O2 deficit is the estimation of the O2 demand of high intensity exercise by extrapolation from VO2 measured during steadystate submaximal exercise. It was hypothesized that O2 deficit could be determined without the need to estimate O2 demand by extrapolation. Ten women performed all-out cycle ergometer exercise tests at each of four power outputs selected so that exhaustion would occur after 90 to 600 s. Power output (W), accumulated VO2 (ml), and time to exhaustion (s) were measured in each test and then fit to the following equation: O2 deficit (ml) = O2 demand (ml.min-1.W-1).time (min).power (W) - accumulated VO2 (ml). This procedure generated values for two parameters (O2 demand and O2 deficit) for each subject. The O2 deficit was also calculated for each individual using conventional methods. The values for O2 deficit obtained using the two methods were correlated (r = .96, p < .01), and the value obtained using the experimental method tended to be larger, t(9) = 2.15, p = .06. It is concluded that O2 demand and O2 deficit can be determined from the results of several high-intensity tests without the need to extrapolate from submaximal exercise to estimate the O2 demands of supramaximal exercise.

Adult↗

The relationship between anaerobic threshold and electromyographic fatigue threshold in college women.

The purpose of this study was to investigate the relationship between anaerobic threshold (Th(an)) and muscle fatigue threshold (EMGFT) as estimated from electromyographic (EMG) data taken from the quadriceps muscles (vastus lateralis) during exercise on a cycle ergometer. The subjects in this study were 20 female college students, including highly trained endurance athletes and untrained sedentary individuals, whose fitness levels derived from their maximal oxygen consumption ranged from 24.9 to 62.2 ml.kg-1.min-1. The rate of increase in integrated EMG (iEMG) activity as a function of time (iEMG slope) was calculated at each of four constant power outputs (350, 300, 250, 200 W), sufficiently high to bring about muscle fatigue. The iEMG slopes so obtained were plotted against the exercise intensities imposed, resulting in linear plots which were extrapolated to zero slope to give an intercept on the power axis which was in turn interpreted as the highest exercise intensity sustainable without electromyographic evidence of neuromuscular fatigue (EMGFT). The Th(an) was estimated from gas exchange parameters during an incremental exercise test on the same cycle ergometer. The mean results indicated that oxygen uptake (VO2) at Than was 1.39 l.min-1, SD 0.44 and VO2 at EMGFT was 1.33 l.min-1, SD 0.57. There was no significant difference between these mean values (P greater than 0.05) and there was a highly significant correlation between VO2 at Than and VO2 at EMGFT (r = 0.823, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Dyspnea ratings for prescribing exercise intensity in patients with COPD.

STUDY OBJECTIVE: We tested the hypothesis that patients with COPD can use dyspnea ratings obtained from a prior graded exercise test as a target to reliably produce specific exercise intensities. DESIGN: Four visits over a 7-week period. SETTING: Pulmonary function and cardiorespiratory exercise laboratory at a university hospital. PATIENTS: Fifteen symptomatic patients with stable COPD. Age was 68 +/- 7 (mean +/- SD) years. FEV1 was 1.12 +/- 0.22 L (45 +/- 8% predicted). INTERVENTIONS: At each visit, patients estimated the heaviness of weights to evaluate their magnitude estimation of a nonrespiratory task; after pulmonary function testing was completed, patients were tested on the cycle ergometer. At estimation trial 1 (day 0), patients estimated the intensity of dyspnea using the 0 to 10 category-ratio scale during an incremental exercise test. Estimation trial 2 (day 5 to 7) was the same as the previous trial. At production trials 1 (day 10 to 14) and 2 (day 40 to 44), patients were instructed to produce specific intensities of dyspnea (ie, dyspnea targets) at 50% and at anaerobic threshold (AT) or 80% of peak oxygen consumption (Vo2) as calculated from results at estimation trial 2. MEASUREMENTS AND RESULTS: Lung function was stable at all visits. Dyspnea ratings were 1.8 +/- 0.9 (range, 1 to 3) at 50% of peak Vo2 and 5.5 +/- 1.5 (range, 4 to 8) at AT/80% of peak Vo2 (17.0 +/- 3.4 mL/kg/min) at estimation trial 2. The individual percent changes in Vo2 at the lower dyspnea target were 12 +/- 19% and 11 +/- 19% for production trials 1 and 2, respectively, compared with estimation trial 2. At the higher dyspnea target, the corresponding individual percent changes in Vo2 were -4 +/- 9% and -7 +/- 11%, respectively. For all 15 patients, there were borderline statistical differences for the Vo2 values at the lower (p = 0.04 and p = 0.07) and at the higher (p = 0.04 for each production trial) dyspnea targets for production trials 1 and 2 compared with estimation trial 2. Two patients showed 50% or greater variability in the calculated exponent for magnitude estimation of weights. In a subgroup analysis of the 13 patients with reproducible magnitude estimation of the heaviness of weights, there were no significant differences in Vo2 for the two production trials compared with estimation trial 2 at both exercise intensities. CONCLUSIONS: Dyspnea ratings obtained from an incremental exercise test can be used as a target for patients with COPD to regulate/monitor the intensity of exercise training. The ability of patients with COPD to achieve a desired Vo2 based on an individual dyspnea target was generally more accurate at the higher exercise level (AT/80% of peak Vo2) compared with the lower intensity (50% of peak Vo2). Acceptable accuracy was maintained over a 5-week time period.

Aged↗

Cyclic analogues of bradykinin. IV. Structure-function relationships in the series of bradykinin cycloanalogues.

A study of the biological activity of six bradykinin and kallidin cycloanalogues has revealed that all of them exhibit prolonged hypotensive activity except the inactive cyclo-(omega-aminododecanoyl-omega-aminododecanoyl-bradykini n) (CADADB) when assayed in anaesthetized rats in vivo. The threshold dose of cyclo-bradykinin (CB) in these experiments was found to be 250 micrograms/kg of body weight. A single dose (500 micrograms/kg) of this cyclopeptide produces a decrease in the arterial pressure of rats up to 40 mm Hg for more than 2 h. The hypotensive action of other cyclopeptides under the same conditions is characterized by the following values: cyclo-[epsilon-(L-Lys1, Gly6)-bradykinin] (CLGB), alpha-L-Arg-cyclo-[epsilon-(L-Lys1, Gly6)-bradykinin] (ACLGB) and cyclo-epsilon-kallidin (CK) - 5 micrograms/kg, 40 mm Hg, over 2 h; cyclo-(omega-aminododecanoyl-bradykinin) (CADB) - 50 micrograms/kg, 250 micrograms/kg, 40 mm Hg, 35 min. Some cyclopeptides appeared to possess myotropic activity in vitro on isolated rat uterus preparations: CB (alpha = 0.52, pD2 = 7.86), CK (alpha = 1.0, pD2 = 7.56), CADB (alpha = 0.81, pD2 = 6.41). CLGB, ACLGB and CADADB failed to show myotropic activity. In contrast to CLGB and CADB, CK was hypotensive in dogs. CB acts as a weak antagonist of bradykinin (pA2 = 5.09 +/- 0.06) on rat uterus in vitro. It is believed that the hypotensive action within this series of compounds is primarily determined by the cycle size, whilst their myotropic activity is due to the presence of a "common" fragment Arg-Pro-Pro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗