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Antral follicle counts are related to age at natural fertility loss and age at menopause.

OBJECTIVE: The variability in ultrasound-based antral follicle counts sized 2-10 mm after allowing for age-related decline is considerable. This may represent differences in actual reproductive age among women. This hypothesis was tested by cohort comparison for distribution of age at occurrence of reproductive events. DESIGN: A model with a nonlinear mean decline with age was fitted to antral follicle counts (AFC) obtained in 163 regularly cycling fertile volunteers. Ages at last child birth and menopause were predicted from the individual AFC by using thresholds to represent these events and the model for decline with age. Distributions of the observed ages at last childbirth (proxy variable for loss of natural fertility) and ages at menopause were obtained from the BALSAC demographic database and the Prospect-EPIC study, respectively. The observed distributions were compared with the predicted distributions by using visual comparison and quantile-quantile plots. Predictions of age at last child and age at menopause were done using percentiles of the modeled AFC distribution for given age, and corresponding percentiles of the predicted distributions of age at these reproductive events, with predictions following from the position of a woman's AFC relative to these percentiles. RESULTS: The predicted distributions of age at last child and age at menopause showed good agreement with the observed distributions in the BALSAC and EPIC cohort. Compared with age alone, antral follicle counts gave some additional information for individual prediction of age at last child and menopause. CONCLUSIONS: The link between declining antral follicle counts and reproductively significant events like loss of natural fertility and menopause is strengthened by the high degree of similarity among the predicted and observed age distributions. Predictive usefulness of this relationship in a clinical setting may be more marginal, except in the case of women who have low AFCs for their age.

Adult↗

Differences in anaerobic performance between boys and men.

The purpose of this study was to compare the anaerobic performance of 11-12 year old prepubescent boys (stage 1; n = 18) using a maximal effort 90 s cycling test to that of adult men (n = 19). Performance was separated into short-term anaerobic power (SAP; work in 10 s), intermediate-term anaerobic capacity (IAC; work in 30 s) and long-term anaerobic capacity (LAC; work in 90 s). Resistance on the Monark cycle ergometer was chosen as the highest tolerable load for the 90 s test and set at 2.6 and 3.8 J. rev-1.kg body mass-1 for boys and men, respectively. Power drop-off (%PD) was determined as the change in 5 s power outputs from 0-90 s. Blood lactates were measured at rest (pretest; BL) and at 2 (BL2) and 5 (BL5) min post test. Absolute and relative (to weight or thigh volume) scores for SAC, IAC and LAC were 33-40% lower in the boys compared to the men (p < 0.001). The men demonstrated significantly greater %PD over the 90 s (32.2%) compared to the 25.3% PD of the boys (p < 0.001), suggesting that the development of fatigue was greater in the men even though power and work outputs were high. Resting BL values were similar for both groups. Mean BL2 and BL5 were higher (p < 0.01) in the men (13.5, SD = 3.4; 12.5, SD = 2.8 mmol.l-1) than in the boys (9.1, SD = 1.7; 8.3, SD = 1.6 mmol.l-1). The anaerobic performance of the boys compared to the men cannot be completely explained by the lower resistance setting used. Although the boys were 50% lighter than the men, their resistance was 70% of that used for the men. The results do not support the contention that children and adults have similar abilities in short term, exhaustive work when corrected for size. Prepubescent boys appear to be limited in their ability to perform short-term as well as intermediate and long term anaerobic exercise compared to adult males.

Adult↗

Exercise intensity during off-road cycling competitions.

PURPOSE: This study was designed to quantify and describe the intensity profile of cross-country mountain-biking races using heart rate (HR) recorded during competitions. METHODS: Nine mountain bikers participated in four cross-country circuit races of international and national levels. Each cyclist was tested before the competitions to determine lactate threshold (LT), the onset of blood lactate accumulation (OBLA4), and the relationship between percentage of maximum HR and percentage of VO(2max). RESULTS: To control for intersubject variability, only the five off-road cyclists who completed all four competitions were included in the statistical analysis. The four races' mean absolute and relative time expressed in percentage of race duration (147 +/- 15 min) spent in the EASY(ZONE) (HR below LT) were 27 +/- 16 min and 18 +/- 10%, in the MODERATE(ZONE) (HR between LT and OBLA4) were 75 +/- 19 min and 51 +/- 9%, and in the HARD(ZONE) (HR above OBLA4) were 44 +/- 21 min and 31 +/- 16%. The average HR was 171 +/- 6 beats x min(-1), corresponding to 90 +/- 3% of maximum (84 +/- 3% of VO(2max). CONCLUSION: This study shows that cross-country events are conducted at very high intensity, especially at the start of the race. Coaches must take into account the distribution of the effort and the high exercise intensity characteristic of mountain-biking cross-country events when prescribing specific training programs.

Adaptation, Physiological↗

Aerobic capacity is associated with 100-day outcome after hepatic transplantation.

The shortage of donor organs highlights the need to better identify patients most likely to benefit from hepatic transplantation. Reduced aerobic capacity (decreased peak oxygen consumption [VO(2)] during symptom-limited cardiopulmonary exercise testing) is frequently present in cirrhosis. Peak VO(2) during cardiopulmonary exercise testing may predict short-term outcome after hepatic transplantation. Symptom-limited testing was performed on a cycle ergometer (continuous ramp protocol) and VO(2) determined using a metabolic cart. One hundred fifty-six patients were tested; 59 subsequently underwent hepatic transplantation. Results showed that survivors and nonsurvivors were similar in age, duration of liver disease, Child-Pugh score, MELD score, resting cardiovascular function, pulmonary function, and gas exchange. The 6 (10.2%) patients dying within 100 days of transplantation were more likely to have reduced aerobic capacity (peak VO(2) <60% predicted and VO(2) at anaerobic threshold [VO(2)-AT] <50% predicted peak VO(2)) compared to survivors (4/6 vs. 7/53, P <.01). Using a multiple logistic regression model controlling for duration and severity of liver disease and time to transplantation, reduced aerobic capacity was independently associated with 100-day mortality. In conclusion, reduced aerobic capacity during cardiopulmonary exercise testing is associated with decreased short-term survival after hepatic transplantation. Further study is needed to determine if cardiopulmonary exercise testing can be used to improve allocation of donor organs. To ensure optimum allocation of donor organs, it is important to identify patients most likely to benefit from transplantation. Investigators have identified a number of preoperative, intraoperative, and postoperative factors that predict increased risk for postoperative mortality. Unfortunately, predictive accuracy has not been high, and the timing of factor identification does not optimize organ utilization. Identification of predictors of survival at the time of listing for transplantation might lead to better resource allocation.

Adult↗

Effects of nutritional state on the expression of radiation injury in two tumor subpopulations obtained from a heterogeneous human colon carcinoma.

Environmental modification of the intrinsic ionizing radiation sensitivity of two tumor cell subpopulations obtained from a single heterogeneous human colon adenocarcinoma was studied. The two subpopulations (termed clones A and D) were grown as monolayers to produce plateau phase cultures. Two different plateau phase growth states were produced by either changing the culture medium daily until maximum density was achieved ("fed" cultures), or by not changing the original medium for the entire duration of growth ("unfed" cultures). Cells were irradiated with graded single doses of X rays to determine survival responses. Using conventional single-hit, multi-target terminology, the extrapolation numbers (n), mean lethal doses (D0, Gy), and quasi-threshold doses (Dq, Gy) for fed and unfed cultures of clone A cells were 23.7, 0.80, and 2.54 (fed); and 9.65, 0.85, and 1.93 (unfed). For fed and unfed cultures of clone D cells these values were: 13.0, 0.76, and 1.94 (fed); and 23.8, 0.73, and 2.30 (unfed). No significant difference was found between the radiation responses of these two tumor subpopulations in the plateau phase of growth, either as fed or unfed cultures. The D0 value for clone D, but not for clone A, was significantly less than the D0 value for cells in exponential growth, indicating that the change from exponential growth to a plateau growth state is accompanied by a change in the intrinsic sensitivity of clone D tumor cells. After establishment of the single dose response curves, we then investigated the ability of clone A and D cells to recover from radiation injury (potentially lethal damage recovery, PLDR) by irradiating plateau phase cultures with a single radiation dose sufficient to reduce survival to about 1%, and then subculturing the cells into fresh medium at times varying from 0-24 hours postirradiation. We found that the maximum increase in survival was seen at 12-24 hours postirradiation, and that the ratio of this maximum survival to the cell survival when subculturing was done immediately after irradiation was 2.7 (fed) and 2.5 (unfed) for clone A cells, and 3.6 (fed) and 3.0 (unfed) for clone D cells. Therefore, whereas clone D cells have a greater ability to express PLDR (by a factor of about 1.3) than clone A cells, the modification of this recovery by the environment was identical, with survival in the fed state being greater than in the unfed state by a factor of 1.2 and 1.1 for clone D and clone A tumor subpopulations, respectively.

Adenocarcinoma↗

Frequency specificity of the human auditory brainstem and middle latency responses using notched noise masking.

This study investigated the frequency specificity of the auditory brainstem and middle latency responses to 80 and 90 dB ppe SPL 500-Hz and 90 dB ppe SPL 2000-Hz tonebursts. The stimuli were brief (2-1-2 cycle) linear-gated tonebursts. ABR/MLRs were recorded using two electrode montages: (1) Cz-nape of neck and (2) Cz-ipsilateral earlobe. Cochlear contributions to ABR wave V-Na and MLR waves Na-Pa and Pa-Nb were assessed by plotting notched noise tuning curves which showed amplitudes and latencies as a function of center frequency of the noise masker [Abdala and Folsom, J. Acoust. Soc. Am. 97, 2394 (1995); ibid. 98, 921 (1995)]. Maxima in the response amplitude profiles for the ABR and MLR to 80 dB ppe SPL tonebursts occurred within one-half octave of the nominal stimulus frequency, with minimal contributions to the responses from frequencies greater than one octave away. At 90 dB ppe SPL, contributions came from a slightly broader frequency region for both stimulus frequencies. Thus, the ABR/MLR to 80 dB ppe SPL tonebursts shows good frequency specificity which decreases at 90 dB ppe SPL. No significant differences exist in frequency specificity of: (1) ABR wave V-Na versus MLR waves Na-Pa and Pa-Nb at either stimulus frequency or intensity; and (2) ABR/MLRs recorded using the two electrode montages.

Auditory Threshold↗

Can estradiol modulate schizophrenic symptomatology?

Using epidemiologic data, in an earlier study we formulated the hypothesis that estrogens can delay the onset of schizophrenia in females by raising the vulnerability threshold for this disease. In animal experiments, Häfner and colleagues found evidence that chronic estradiol treatment reduces the sensitivity of dopamine (D2) receptors in the brain. In the clinical study presented in this article, as a further step we examined the antipsychotic properties of estradiol in human females by testing whether schizophrenic symptomatology varies with estradiol serum levels throughout the menstrual cycle. We examined 32 acutely admitted female schizophrenia patients (Present State Examination/CATEGO diagnosis, ICD-9) with a history of regular menstrual cycles, ages 18 to 43 (mean = 30.5), during their hospital stays (3-8 weeks), analyzing hormonal parameters and applying various rating scales for psychopathology every 7 days. In all patients, estradiol serum levels were markedly reduced as compared with the normal population, and fluctuations throughout the cycle were dampened. Nevertheless, a significant association emerged between estradiol levels, on the one hand, and psychopathology scores, on the other--that is, the psychiatric symptomatology as assessed by the clinical psychiatrist (Brief Psychiatric Rating Scale, p < or = 0.01), behavior on the ward as assessed by the nursing staff (Nurses' Observation Scale for Inpatient Evaluation p < or = 0.01), paranoid tendencies and general well-being as assessed by the patients themselves (Paranoid-Depressivitäts-Skala paranoid score p < or = 0.05; Befindlichkeits-Skala p < or = 0.05). Psychopathology seems to improve when estradiol levels rise, and vice versa. These findings can be interpreted as further evidence for a protective effect of estrogens in schizophrenia, possibly due to the known anti-dopaminergic activities of these hormones.

Adolescent↗

Intensity-dependent activation of the primary auditory cortex in functional magnetic resonance imaging.

PURPOSE: The purpose of this study was to investigate the activation patterns of the primary auditory cortex in response to varying intensities of pure tone stimuli. METHOD: A 1,000-Hz pure tone stimulus was delivered monaurally to the right ear of 12 normal-hearing right-handed volunteers in 20-second on-off cycles. Stimuli were applied at 20 and 50 dB hearing level (HL) above threshold in 12 subjects and at 0, 20, 40, and 50 dB HL above threshold in 6 subjects. Functional magnetic resonance imaging (fMRI) data were obtained using a 1.5-T scanner and echoplanar imaging. Activated pixels were identified in the transverse temporal gyrus (TTG) of both hemispheres in response to pure tone stimuli at each intensity level using cross-correlation analysis (0.6; P < 0.0001). RESULTS: Of the 24 right and left TTGs imaged (n = 12), activation to pure tone stimuli at 20 and 50 dB HL above threshold was seen in 46% and 79% of TTGs, respectively, with bilateral hemispheric activation in 27% and 64% of subjects, respectively. The mean numbers of activated voxels were 4.0 and 13.0, respectively. Of the 12 right and left TTGs imaged at 0, 20, 40, and 50 dB HL above threshold, activation was seen in 33%, 42%, 58%, and 75% of TTGs, respectively. The mean numbers of activated voxels were 5.8, 3.2, 9.8, and 15.3, respectively. There was a nonsignificant trend toward contralateral (left) dominant TTG activation with increased tone intensity. CONCLUSION: Our results show an increased likelihood of TTG activation, increased TTG activation volume, and increased bilateral hemisphere TTG activation with increasing pure tone intensity. Our results suggest that the primary auditory cortex reflects or is directly involved in the central processing of sound intensity and that varying the intensity of even simple stimuli can alter the patterns of fMRI activation in auditory cortex.

Acoustic Stimulation↗

Nitric oxide production during exercise in chronic heart failure.

In chronic heart failure (CHF), the ventilatory response is increased compared with normal. This response is, in part, caused by reduced perfusion to ventilated lung. Nitric oxide (NO) is a potent vasodilator and may have an important role in pulmonary vasodilatation during exercise. NO is present in exhaled air. The amount of NO in exhaled air, when breathing NO-free compressed air, is known to increase in normal subjects during exercise. In this study, we quantified NO output in exhaled air in patients with CHF during exercise. Six patients with CHF (New York Heart Association Class II and III; two with dilated cardiomyopathy, three with ischemic heart disease, and one with hypertensive heart disease) and six normal subjects were studied with a symptom-limited incremental exercise test on a cycle ergometer. Oxygen uptake (VO2), carbon dioxide output (VCO2), and minute ventilation (VE) were measured breath by breath with a mass spectrometer, flow meter, and computer. The NO concentration was continuously measured in mixed expired air by chemiluminescence. Peak exercise work rate was lower in patients with CHF than in normal subjects (71.3 +/- 41.6 W vs 257.0 +/- 49.7 W; p < 0.01). Patients with CHF showed a higher VE/VCO2 level at peak exercise than normal subjects (CHF, 47.0 +/- 10.7; normal subjects, 35.6 +/- 5.2; p < 0.01). NO concentration of exhaled air at rest was lower in CHF patients than in normal subjects (4.0 +/- 2.2 ppb vs 10.5 +/- 6.2 ppb, respectively; p < 0.05). NO output from the respiratory tract (VNO) was significantly lower in patients with CHF compared with normal subjects at rest (45.3 +/- 24.3 nl/min, 117.5 +/- 60.1 nl/min, respectively, p < 0.05), and although it increased during exercise, it did not increase in patients with CHF as much as in normal subjects (75.3 +/- 43.4 nl/min vs 512.9 +/- 253.6 nl/min, respectively; p < 0.01). The increase above rest (exercise/rest) was smaller in patients with CHF than in normal subjects (2.10 +/- 1.92 vs 4.81 +/- 2.67, p < 0.05). These data support the concept that the smaller increase in NO production (VNO) during exercise may be responsible for a blunted vasodilation in patients with CHF, resulting in a smaller reduction in dead space/tidal volume and VE/VCO2 at the lactic acidosis threshold than normal. This finding may play a role in the abnormally high ventilatory response to exercise in patients with CHF.

Adult↗

Impeding O(2) unloading in muscle delays oxygen uptake response to exercise onset in humans.

We tested whether the leftward shift of the oxygen dissociation curve of hemoglobin with hyperpnea delays the oxygen uptake (VO(2)) response to the onset of exercise. Six male subjects performed cycle ergometer exercise at a work rate corresponding to 80% of the ventilatory threshold (VT) VO(2) of each individual after 3 min of 20-W cycling under eupnea [control (Con) trial]. A hyperpnea procedure (minute ventilation = 60 l/min) was undertaken for 2 min before and during 80% VT exercise in hypocapnia (Hypo) and normocapnia (Normo) trials. In the Normo trial, the inspired CO(2) fraction was 3% to prevent hypocapnia. The subjects completed two repetitions of each trial. To determine the kinetic variables of VO(2) and heart rate (HR) at the onset of exercise, a nonlinear least-squares fitting was applied to the data averaged from two repetitions by a monoexponential model. The end-tidal CO(2) partial pressure before the onset of exercise was significantly lower in the Hypo trial than in the Con and Normo trials (22 +/- 1 vs. 38 +/- 3 and 36 +/- 1 mmHg, respectively, P < 0.05). The time constant of VO(2) and HR was significantly longer in the Normo trial (28 +/- 7 and 39 +/- 18 s, respectively) than in the Con trial (21 +/- 7, 34 +/- 16 s, respectively, P < 0.05). The VO(2) time constant of the Hypo trial (37 +/- 12 s) was significantly longer than that of the Normo trial, although no significant difference in the HR time constant was seen (Hypo, 41 +/- 28 s). These findings suggested that respiratory alkalosis delayed the kinetics of oxygen diffusion in active muscle as a result of the leftward shift of the oxygen dissociation curve of hemoglobin. This supports an important role for hemoglobin-O(2) offloading in setting the VO(2) kinetics at exercise onset.

Adult↗

Progressive mechanical ventilatory constraints with aging.

To investigate the progressive nature of mechanical ventilatory constraints with aging, we studied 20 young (age 39 +/- 3 yr), 14 senior (70 +/- 2 yr), and 11 elderly (88 +/- 2 yr) men and women during exercise. All subjects had normal pulmonary function and performed graded cycle ergometry to exhaustion. Minute ventilation (V E), lung volume, and expiratory airflow limitation (EAFL) were measured during each 1-min increment in work rate. Data were analyzed by two-way analysis of variance (ANOVA; age x gender) at rest, ventilatory threshold (VTh), and peak exercise. If an interaction was present, each gender was analyzed with a one-way ANOVA. Aging resulted in an increased V E for a given submaximal work rate, although V E during peak exercise was lowest in the elderly group (p < 0.01). End-expiratory lung volume (EELV, % of TLC) in men increased progressively with age and all groups were different at VTh (p < 0.01) and peak exercise (p < 0.01). In women, EELV (% of TLC) also increased with aging, the senior and elderly subjects had a greater EELV at VTh (p < 0.01) and peak exercise (p < 0.01) than the young group. Additionally, the normal decrease in EELV during the early stages of exercise was not observed in elderly subjects. End-inspiratory lung volume (EILV) also progressively increased with aging; senior and elderly subjects had a higher EILV at rest (p < 0.05), VTh (p < 0.01), and peak exercise (p < 0.01) than young subjects. EAFL (% of VT) increased with aging; elderly subjects experienced greater EAFL at rest (p < 0.05), VTh (p < 0.01), and peak exercise (p < 0.01) than both young and senior subjects. We conclude that mechanical ventilatory constraints are progressive with aging, elderly subjects demonstrating marked mechanical ventilatory constraints during exercise. The impact of these constraints on exercise tolerance cannot be determined from this investigation and remains unclear.

Adult↗

Neurogenic vestibular evoked potentials using a tone pip auditory stimulus.

OBJECTIVES: To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a tone pip auditory stimulus. METHODS: Fourteen neurologically normal volunteers (Age range 26-45 years, 10 females and 4 males), and two patients with sensorineural hearing loss and possible multiple sclerosis respectively, were examined. Two channel recordings were obtained, the first channel being P3 referred to Fpz, and the second channel being P4 referred to Fpz. A 1 kHz tone pip stimulus with two cycles was delivered via headphones monoaurally with contralateral masking noise. RESULTS: A consistent negative wave with a mean absolute latency of 4.72 msec was obtained, which we have named N5. 25% of the ears tested had better responses at the ipsilateral parietal electrode. In the patient with bilateral sensorineural hearing loss, NVESTEPs was present, suggesting that the NVESTEP is not a cochlear response. In the patient with possible multiple sclerosis, an abnormal NVESTEP response and a normal BAEP response were found. CONCLUSION: Use of a tone-pip rather than a click auditory stimulus allows a lower click intensity to be used in the production of NVESTEP responses, leads to a shorter testing time, and is therefore more comfortable for the patient. This study adds to our impression that the NVESTEP may be a physiological response that can be used to assess the vestibular system and is different from the BAEP response. Further testing in patients with symptoms of dizziness and with disorders specific for the vestibular nerve is required.

Acoustic Stimulation↗

Effects of reduced ambient temperature on fat utilization during submaximal exercise.

PURPOSE: The influence of cold air exposure on fuel utilization during prolonged cycle exercise was investigated. METHODS: Nine male subjects cycled for 90 min in ambient temperatures of -10 degrees C, 0 degrees C, 10 degrees C, and 20 degrees C. External work performed between conditions was constant. Mean oxygen consumption (VO2) over the 90 min in the 20 degrees C trial corresponded to 64 +/- 5.8% VO2peak. RESULTS: Although mean skin temperature was different between trials (P < 0.05), rectal temperatures were not different. At -10 degrees C and 0 degrees C, the respiratory exchange ratio was higher compared with 10 degrees C and 20 degrees C (0.98 +/- 0.01 and 0.97 +/- 0.01 vs 0.92 +/- 0.01 and 0.91 +/- 0.01; P < 0.05). The associated rates of fat oxidation were lower at -10 degrees C and 0 degrees C compared with 10 degrees C and 20 degrees C (0.15 +/- 0.06 and 0.17 +/- 0.06 vs 0.35 +/- 0.06 and 0.40 +/- 0.04 g.min-1; P < 0.05). Blood glycerol was lower at -10 degrees C and 0 degrees C compared with 20 degrees C (P < 0.05); mean values were 0.13 +/- 0.0, 0.13 +/- 0.0, and 0.18 +/- 0.0 mmol.L-1 for the -10 degrees C, 0 degrees C, and 20 degrees C trials, respectively. Mean VO2 was lower in the -10 degrees C trial than the 20 degrees C trial (2.53 +/- 0.06 vs 2.77 +/- 0.09. L.min-1; P < 0.05). Mean blood glucose concentrations were lower at -10 degrees C than 20 degrees C (4.9 +/- 0.2 vs 5.3 +/- 0.1 mmol.L-1; P < 0.05). Although plasma epinephrine concentrations were greater during the 20 degrees C trial compared with all other trials (P < 0.05), plasma norepinephrine did not differ between trials. CONCLUSION: The diminished fat oxidation at colder temperatures potentially reflects a reduction in lipolysis and/or mobilization of FFA or impairment in the oxidative capacity of the muscle.

Adipose Tissue↗

Excess postexercise oxygen consumption and recovery rate in trained and untrained subjects.

The purpose of this study was to determine whether aerobic fitness level would influence measurements of excess postexercise oxygen consumption (EPOC) and initial rate of recovery. Twelve trained [Tr; peak oxygen consumption (VO2 peak) = 53.3 +/- 6.4 ml . kg-1 . min-1] and ten untrained (UT; VO2 peak = 37.4 +/- 3.2 ml . kg-1 . min-1) subjects completed two 30-min cycle ergometer tests on separate days in the morning, after a 12-h fast and an abstinence from vigorous activity of 24 h. Baseline metabolic rate was established during the last 10 min of a 30-min seated preexercise rest period. Exercise workloads were manipulated so that they elicited the same relative, 70% VO2 peak (W70%), or the same absolute, 1.5 l/min oxygen uptake (VO2) (W1.5), intensity for all subjects, respectively. Recovery VO2, heart rate (HR), and respiratory exchange ratio (RER) were monitored in a seated position until baseline VO2 was reestablished. Under both exercise conditions, Tr had shorter EPOC duration (W70% = 40 +/- 15 min, W1.5 = 21 +/- 9 min) than UT (W70% = 50 +/- 14 min; W1.5 = 39 +/- 14 min), but EPOC magnitude (Tr: W70% = 3.2 +/- 1.0 liters O2, W1.5 = 1.5 +/- 0.6 liters O2; UT: W70% = 3.5 +/- 0.9 liters O2, W1.5 = 2.4 +/- 0.6 liters O2) was not different between groups. The similarity of Tr and UT EPOC accumulation in the W70% trial is attributed to the parallel decline in absolute VO2 during most of the initial recovery period. Tr subjects had faster relative decline during the fast-recovery phase, however, when a correction for their higher exercise VO2 was taken. Postexercise VO2 was lower for Tr group for nearly all of the W1.5 trial and particularly during the fast phase. Recovery HR kinetics were remarkably similar for both groups in W70%, but recovery was faster for Tr during W1.5. RER values were at or below baseline throughout much of the recovery period in both groups, with UT experiencing larger changes than Tr in both trials. These findings indicate that Tr individuals have faster regulation of postexercise metabolism when exercising at either the same relative or same absolute work rate.

Adult↗

The detection and evaluation of aneugenic chemicals.

Although aneuploidy makes a significant contribution to both somatic and inherited disease the mechanisms by which environmental chemicals may induce numerical chromosome aberrations are only poorly defined. The European Union Project was aimed to further our understanding of those chemical interactions with the components of the mitotic and meiotic cell division cycle which may lead to aneuploidy and to characterise the parameters such as cellular metabolism which may influence the activity of aneugenic chemicals. C-mitosis can be induced by the highly lipophilic polychlorinated biphenyl and the completion of mitosis and cleavage can be modified by agents which deplete cellular levels of reduced glutathione. Modifications of the fidelity of chromosome segregation were produced by inhibiting the functioning of topoisomerase II during chromatid separation. In contrast, the modification of centromere integrity resulted in chromosome breakage as opposed to disturbance of segregation. Modifiers of tubulin assembly and centriolar functioning in somatic cells such as acrylamide, vinblastine and diazepam reproduced their activity in rodent bone marrow and male germ cells. The analysis of chromosome malsegregation in Aspergillus nidulans by a structurally related series of halogenated hydrocarbons was used to develop a QSAR model which had high predictive value for the results of fungal tests for previously untested related chemicals. Metabolic studies of potential aneugens in genetically engineered human lymphoblastoid cells demonstrated the detoxification of the aneugenic activity of chloral hydrate and the activation of 2,3-dichlorobutane, 1,1,2-trichloroethane and trichloroethylene by Phase I biotransforming enzymes. Cell transformation studies in Syrian hamster dermal cultures using a panel of 22 reference and or potential aneugens indicated that 15 of the 22 produced positive results following single exposures. Five of the aneugens which were negative following single exposures produced positive results where cultures were continuously exposed for up to 6 weeks to low concentrations following a single non-transforming exposure to the mutagen dimethyl sulphate. The transformation studies indicate that a significant proportion of chemical aneugens are potential complete carcinogens and/or co-carcinogens. To optimise the enumeration of chromosomes following exposure to potential chemical aneugens whole chromosome paints and centromere specific probes suitable for use in fluorescence in situ hybridisation (FISH) were developed for the rat, mouse and Chinese hamster and selected human probes evaluated for their suitability for routine use. Molecular chromosome probes were used to develop protocols for enumerating chromosomes in metaphase cells and centromeres and micronuclei in interphase cells. The analysis of segregation of specific centromeres in binucleate cells following cytochalasin B treatment was shown to be a potentially valuable system for characterising non-disjunction following chemical exposure. Whole chromosome paints and centromere specific probes were used to demonstrate the presence of dose-response thresholds following treatment with a reference panel of spindle inhibiting chemicals. These data indicate that the FISH technology is suitable for evaluating the relative hazards of low-dose exposures to aneugenic chemicals.

Aneuploidy↗

Correlated variations in EEG pattern and visual responsiveness of cat lateral geniculate relay cells.

1. Simultaneous recordings of the EEG and the visual activity of cat dorsal lateral geniculate nucleus (dLGN) relay cells were analysed for covariance. Sliding time-window analyses were performed in parallel for the EEG power spectrum and single unit visual activity. The EEG power ratio (EEG-PR) of low (1-8 Hz) to high (20-40 Hz) frequencies was chosen to achieve a quantitative measure of the EEG which could be compared with the spike rate of a dLGN unit at any time. A high EEG-PR value indicates a synchronized EEG dominated by low frequencies (delta waves and sleep spindles), a low value indicates a less synchronized EEG. 2. In the anaesthetized animal, two different underlying patterns of activity in the EEG-PR were found: slow gradual changes (slow gradations) and oscillatory changes. In many cases both were accompanied by correlated variations in dLGN spike rate, either for overall activity or for burst firing. 3. The slow gradations appear for long time periods of up to 200 s and, in most cases (76.3 %), show a negative correlation between EEG-PR and overall spike rate, but predominantly a positive correlation for burst firing (85.1 %). 4. The oscillatory changes, which have not previously been reported, appear as temporally well-coupled variations in EEG-PR and spike rate with a stable cycle length within the range 4-10 s. In about 77 % of correlated changes the temporal delay between the change in EEG-PR and that of the spike rate was less than +/- 1.0 s. 5. During simultaneous recordings from two dLGN cells the variations in spike rate tend to show the same sign of correlation with respect to the EEG pattern. This relationship is more pronounced with the slow gradations than with the oscillatory changes. 6. Slow gradations in the spectral composition of the EEG may indicate global transitions between different stages within the sleep-wake cycle, reflecting the well-known influences of the brainstem arousal system. The oscillations in the spectral composition of the EEG are accompanied by gradual variations in thalamic transmission mode and are more likely to be due to involvement of a local feedback system via the thalamo-cortico-thalamic loop. The difference between the effects on overall and burst firing activity supports the notion that phasic (burst firing) and tonic visual responses may play distinctive roles in information processing, which are functionally related to the animal's behavioural state.

Animals↗

The y-intercept of the critical power function as a measure of anaerobic work capacity.

When bouts of muscular work are performed to exhaustion at different intensities, the slope of the regression of maximal work (work limit) on maximal time (time limit) is referred to as critical power (CP). The y-intercept of this function is considered to represent anaerobic work capacity (AWC). The purpose of this investigation was to examine the relationship between the y-intercept from the critical power curve and measures of AWC (total work accomplished, maximal blood lactate and post-exercise venous blood pH) gained from repeated, maximal exercise. Nine male volunteers of moderately high training status (VO2 max 4.45 +/- 0.251/min) completed three cycle ergometer tests to exhaustion (at 300, 350 and 400 W) for the determination of CP. A second cycle ergometer task involved repeated maximal effort (against 0.075 N/kg body mass) over five 1 min periods. Five min of passive recovery separated each exercise bout, at the end of which capillary blood was collected for lactate analysis. On completion of the fifth bout, venous blood was sampled for the determination of blood pH. Total accumulated work provided a performance estimate of AWC which, together with blood lactate and pH, was compared to the y-intercept. Correlation analysis revealed a significant relation between the y-intercept and total work accomplished (r = 0.74; p less than 0.05), while post-exercise venous blood pH was positively related to both the y-intercept (r = 0.92; p less than 0.01) and the accumulated work recorded (r = 0.92; p less than 0.01). No significant correlation between peak blood lactate and work was found (r = 0.16; ns), although a relation between post-exercise venous blood pH and VO2 max was established (r = 0.84; p less than 0.05). The capacity for high intensity interval work was well represented by the y-intercept in active males. Furthermore, the relations between blood pH and both the y-intercept and accumulated work suggest that either improved buffering or a greater contribution of aerobic metabolism to the energy yield may have been responsible for the more successful performances in the interval exercise.

Acid-Base Equilibrium↗

High-intensity endurance training in 20- to 30- and 60- to 70-yr-old healthy men.

Factors contributing to maximal incremental and short-term exercise capacity were measured before and after 12 wk of high-intensity endurance training in 12 old (60-70 yr) and 10 young (20-30 yr) sedentary healthy males. Peak O2 uptake in incremental cycle ergometer exercise increased from 1.60 +/- 0.073 to 2.21 +/- 0.073 (SE) l/min (38% increase) in the old subjects and from 2.54 +/- 0.141 to 3.26 +/- 0.181 l/min (29%) in the young subjects. Peak cardiac output, estimated by extrapolation from a series of submaximal measurements by the CO2 rebreathing method, increased by 30% (from 12.7 to 16.5 l/min) in the old subjects, associated with a 6% increase (from 126 to 135 ml/l) in arteriovenous O2 difference; in the young subjects there were equal 14% increases in both variables (18.0 to 20.5 l/min and 140 to 159 ml/l, respectively). Submaximal mean arterial pressure and cardiac output were lower posttraining in the old subjects; total vascular conductance and cardiac stroke volume increased. Although peak power at the start of a short-term maximal isokinetic test did not change, total work accomplished in 30 s at a pedaling frequency of 110 revolutions/min increased in both groups, from 11.2 to 12.6 kJ and from 15.7 to 16.9 kJ in the old and young, respectively; fatigue during the 30-s test was less, and postexercise plasma lactate concentrations were lower. In older subjects, increases in aerobic power after high-intensity endurance training are at least as large as in younger subjects and are associated with increases in vascular conductance, maximal cardiac output, and stroke volume.

Adult↗