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PubMed1987

Exact results for the average dynamic behavior of some non-linear neural networks.

We have studied the global dynamic behavior of neural-like networks of synchronous threshold elements by writing a master equation as a function of parameter values using statistical methods. Exact results for highly connected networks and no correlation are obtained, showing that in this case (contrary to previous results) the average activity can only display simple stable behaviour, the sole exception being special cases of a slow passage through a tangent bifurcation, and a limit cycle of length two. By introducing an appropriate probabilistic hypothesis, we also study the average activity and correlation for highly connected networks with the topology of a (Cayley) tree. In this case the dynamic is ruled by a pair of coupled equations linking activity and correlation, and the tendency is for the correlation to disappear over time. However, under reasonable biological conditions, this tendency will be extremely slow, giving rise to a region of pseudo-stability.

Animals↗
PubMed1984

Gas exchange response to exercise in children.

We measured the gas exchange response to exercise in 109 normal children (51 girls and 58 boys, ranging in age from 6 to 17 yr old) using noninvasive breath-by-breath techniques. The protocol consisted of cycle ergometry in which the work rate increased in a linear manner (ramp forcing function) until the limit of the subject's tolerance was reached. We measured the maximal oxygen uptake (VO2max) and the VO2 at the anaerobic threshold (AT). We found that both of these parameters were highly correlated with increasing height, and that for both the AT and VO2max, the values for boys were significantly higher than girls. We compared our results of VO2max to those obtained by Astrand over 30 years ago using different techniques. When boys and girls were considered together, there were no significant differences between our study and Astrand's; however, girls in our study had significantly lower values for VO2max than did girls in Astrand's study. These data provide normal values for both VO2max and AT and can be used to evaluate the exercise impairment resulting from disease in children.

Adolescent↗
PubMed1982

Alterations in anaerobic threshold as the result of endurance training and detraining.

The response of anaerobic threshold (AT) to endurance training and detraining was studied in 21 males (mean age = 25 yr). Members of the exercise group trained on a cycle ergometer at 80% of maximal oxygen uptake (VO2max) for 30 min four times per week for 9 wk. Nine weeks of detraining followed. A step-wise incremented cycle ergometer test was used to measure maximal and submaximal values of metabolic variables at 3-wk intervals. The criterion for determination of the onset of metabolic acidosis was a systematic increase in the ventilatory equivalent for O2 (VE/VO2) without an increase in the ventilatory equivalent for CO2 (VE/VCO2). Significant increases and decreases of VO2max for the exercise group during training and detraining, respectively, were revealed by ANOVA. Following 9 wk of training, elevations of 70.4% and 19.4% had occurred in AT expressed as absolute VO2 (AT l . min-1) and percent of VO2max (AT-VO2), respectively. The latter change was not statistically significant. Losses of training gains in AT (l . min-1) were significant after 6 and 9 wk of detraining. The results of this study indicate that 9 wk of training is of sufficient duration to cause a significant alteration in AT. Loss of this training gain occurs rapidly and appears to be similar to changes in VO2max.

Acidosis, Respiratory↗
PubMed1991

Chronic stability of bipolar epicardial plunge electrodes in dogs.

We constructed and surgically implanted 114 chronic bipolar epicardial plunge electrodes for programmed left ventricular stimulation in closed chest dogs; 88 electrodes could be analyzed in animals surviving infarct surgery. Electrode plunges were constructed of silver wire, with conduction strands of silver-plated copper wire, in medical grade silicone tubing. Electrodes were implanted epicardially through left thoracotomy and secured with prolene. Wires exited the fifth intercostal space and were tunneled subcutaneously and secured at the dorsal aspect of the neck. Baseline thresholds (mA) were recorded at a paced cycle length of 300 ms and pulse duration of 1 ms. At least 5 days after implantation, under light Nembutal sedation, thresholds were reassessed before programmed stimulation. Each lead was tested repeatedly over 5-177 (mean 28) days. The number of leads decreased with time due to animal attrition from ventricular arrhythmias. Mean pacing threshold at implantation was 0.25 mA. Mean and median threshold values reached plateau after 1 week and showed little change thereafter for the duration of the study. More than 50% of the leads maintained thresholds less than 1.5 mA through the entire study. In animals that survived, 86% of the electrodes remained useful for the duration of the protocol. These data support the use of this electrode system as effective and reliable for chronic electrophysiologic studies in dogs.

Animals↗
PubMed1992

Estradiol and progesterone during exercise in healthy untrained women.

Ten eumenorrheic nonathletic women, aged 21-25, were studied on the 8th day following the LH peak in three consecutive cycles. Plasma level and metabolic clearance rate (MCR) of estradiol (E2) and progesterone (P) were measured before and during a 2-h continuous treadmill test at a speed corresponding to 70% of their running speed at anaerobic threshold on three separate occasions. A significant decrease of plasma level of the hormones (-30% and -40%, respectively, P less than 0.01; mean) from resting values was found, while their metabolic clearance rate increased significantly [E2-MCR from 1017 l.d-1 to 1312 l.d-1 (+29%), P less than 0.001; mean; P-MCR from of 2061 l.d-1 to 2988 l.d-1 (+45%), P less than 0.003; mean]. The increase in MCR of the two hormones was significantly correlated with the increase in heart rate and systolic blood pressure accompanying the beginning of the exercise test.

Adult↗
PubMed1983

Slower Adaptation of VO2 to steady state of submaximal exercise with beta-blockade.

The kinetics of oxygen uptake (VO2) were assessed in 17 normal subjects with beta-blockade and placebo. beta-blockade was achieved with either 50 mg oral metoprolol or 40 mg oral propranolol, each twice per day. Tests were conducted on the cycle ergometer at work rates approximating 80% of the work rate at ventilatory anaerobic threshold. Work rate was initiated as a square wave starting from prior rest. Data obtained 48 h, 1 week, and 4 weeks after starting drug or placebo were pooled to increase the number of points for regression analysis of kinetic parameters. While there were no differences in the plateau values for VO2 with and without beta-blockade, the rate of adaptation to steady state was significantly slower with beta-blockade than with placebo (P less than 0.05). This resulted in an increase of oxygen deficit by approximately 200 ml O2. Cardiac output measured by CO2 rebreathing was significantly reduced by beta-blockade (metoprolol by 4.1%, propranolol by 12.2%, both P less than 0.05). Blood lactate concentration was unaffected by beta-blockade. It was concluded that the influence of beta-blockade on the oxygen transport system was responsible for the significantly slower increase of VO2 to steady state in submaximal exercise.

Adult↗
PubMed2003

Real-time RT-PCR methodology for quantification of thiopurine methyltransferase gene expression.

OBJECTIVE: The aim of the present study was to develop a real-time reverse-transcription polymerase chain reaction (RT-PCR) methodology for the quantification of thiopurine methyltransferase (TPMT) gene expression in whole blood and compare it with the TPMT enzyme activity measured in red blood cells. METHODS: TPMT gene expression was quantified relative to the housekeeping gene cyclophilin (huCYC) and expressed as a TPMT/huCYC ratio. TPMT activity in red blood cells was determined by measuring the formation rate of 6-(14)C-methylmercaptopurine from 6-MP using S-adenosyl-L-((14)C-methyl)-methionine as methyl donor. Thirty-nine individuals were included in the study. A cut-off value of 9 U/ml pRBC was used to distinguish intermediate TPMT enzyme activity from high TPMT enzyme activity. RESULTS: Sequencing of the real-time RT-PCR amplicon proved that the method was specific for the TPMT cDNA, without co-amplification of the highly similar TPMT processed pseudogene. The intra-assay coefficients of variation (CVs), as determined by the threshold cycle, were 0.7% for TPMT and 0.5% for huCYC. The interassay CVs were 1.5% for TPMT and 4.0% for huCYC. The intra- and interassay CVs, as determined by the TPMT/huCYC ratio, were 8.6% and 25%, respectively. There was a statistically significant correlation between TPMT enzyme activity and mRNA level in blood cells from individuals with an enzyme activity above 9 U/ml pRBC (r(s)=0.66, P=0.0001). However, we did not find any statistically significant correlation in individuals with lower enzyme activity or when analysing the whole population. CONCLUSION: We present a specific and robust real-time RT-PCR method for quantifying TPMT gene expression. The method may be used for studies on TPMT gene regulation.

Erythrocytes↗
PubMed2006

Heroin epidemics, treatment and ODE modelling.

The UN [United Nations Office on Drugs and Crime (UNODC): World Drug Report, 2005, vol. 1: Analysis. UNODC, 2005.], EU [European Monitoring Centre for Drugs and Drug Addiction (EMCDDA): Annual Report, 2005.http://annualreport.emcdda.eu.int/en/home-en.html.] and WHO [World Health Organisation (WHO): Biregional Strategy for Harm Reduction, 2005-2009. HIV and Injecting Drug Use. WHO, 2005.] have consistently highlighted in recent years the ongoing and persistent nature of opiate and particularly heroin use on a global scale. While this is a global phenomenon, authors have emphasised the significant impact such an epidemic has on individual lives and on society. National prevalence studies have indicated the scale of the problem, but the drug-using career, typically consisting of initiation, habitual use, a treatment-relapse cycle and eventual recovery, is not well understood. This paper presents one of the first ODE models of opiate addiction, based on the principles of mathematical epidemiology. The aim of this model is to identify parameters of interest for further study, with a view to informing and assisting policy-makers in targeting prevention and treatment resources for maximum effectiveness. An epidemic threshold value, R(0), is proposed for the drug-using career. Sensitivity analysis is performed on R(0) and it is then used to examine the stability of the system. A condition under which a backward bifurcation may exist is found, as are conditions that permit the existence of one or more endemic equilibria. A key result arising from this model is that prevention is indeed better than cure.

Adolescent↗
PubMed1976

Time course of changes in ventricular fibrillation threshold in myocardial infarction: characteristics of acute and slow occlusion with respect to the collateral vessels of the heart.

The time course of the changes in ventricular fibrillation threshold (VFT) was determined in 28 dogs by means of electrical stimulation, triggered from the R wave, with DC square wave pulse series (of 140 ms duration) inserted into the vulnerable period of the cardiac cycle. After acute coronary occlusion there was a sudden decrease in the VFT followed by a slow increase such that 30 min after the ligation pre-occlusion values of VFT were reached. The magnitude of the decrease in VFT depended upon the collateral blood supply. There were no other changes in VFT during the remaining course of the experiment. Following slow coronary occlusion the first arrhythmic phase was not detectable. Any decreases in VFT that occurred were smaller and of shorter duration than those occurring after acute occlusion and were independent of the extent of the collateral blood supply.

Angiocardiography↗
PubMed2003

Early effects of short-term aerobic training. Physiological responses to graded exercise.

AIM: The aim of this study was to find out how early the moderate training effects appear and to check the hypothesis that familiarization with exercise protocol may contribute to an early physiological responses to training in previously sedentary subjects. METHODS: Twelve male, sedentary volunteers (22.0+/-0.7 yrs) were submitted to 3 weeks of a bicycle ergometer training, consisting of 45 min of exercise (at 70% VO(2)max), 3-4 times a week. The subjects performed 4 incremental exercise tests until volitional exhaustion: 2 before training (C1 and C2), and then after 1 (T1) and 3 (T3) weeks of training. During exercise HR, VO(2), electrical activity (EMG) of rectus femoris, biceps femoris, soleus and trapezius muscles were recorded and blood samples were taken for blood lactate (LA) determination. RESULTS: Already after 1 week of training HR decreased (p<0.05) with a further decline after 3 weeks the training (p<0.01). Maximal work load after 3 weeks of training increased to 277+/-10.4 W vs 250+/-9.5 W (p<0.05), VO(2)max achieved higher values than in C1 and C2 tests (p<0.05) and LA and EMG thresholds were elevated (p<0.05). CONCLUSION: A decrease in the resting and submaximal heart rate is the earliest effect of increased physical activity. Familiarization to exercise protocol decreased EMG of biceps femoris and soleus muscles during exercise, but did not influence that of rectus femoris muscle the most engaged during cycling.

Adaptation, Physiological↗
PubMed2005

Dissecting systems-wide data using mixture models: application to identify affected cellular processes.

BACKGROUND: Functional analysis of data from genome-scale experiments, such as microarrays, requires an extensive selection of differentially expressed genes. Under many conditions, the proportion of differentially expressed genes is considerable, making the selection criteria a balance between the inclusion of false positives and the exclusion of false negatives. RESULTS: We developed an analytical method to determine a p-value threshold from a microarray experiment that is dependent on the quality and design of the data set. To this aim, populations of p-values are modeled as mathematical functions in which the parameters to describe these functions are estimated in an unsupervised manner. The strength of the method is exemplified by its application to a published gene expression data set of sporadic and familial breast tumors with BRCA1 or BRCA2 mutations. CONCLUSION: We present an objective and unsupervised way to set thresholds adapted to the quality and design of the experiment. The resulting mathematical description of the data sets of genome-scale experiments enables a probabilistic approach in systems biology.

Breast Neoplasms↗
PubMed1993

Evaluating the economic damage threshold for bont tick (Amblyomma hebraeum) control in Zimbabwe.

Controlling ticks and tick-borne diseases by frequent applications of acaricides (e.g., dipping) is costly, and can leave treated livestock vulnerable to epizootics of tick-borne diseases should the system of applying acaricides break down. The concept of only applying acaricides on an infrequent (strategic) basis often relies on the target tick population displaying a seasonal cycle. However, as adult bont tick (Amblyomma hebraeum) infestations in Zimbabwe's lowveld do not have a strictly seasonal pattern of occurrence, it is recommended that tick control only be applied when bont tick infestations are equal to, or greater than, their economic damage threshold. The economic damage threshold is the minimum average weekly standard female tick burden sufficient to cause damage equal in dollar value to the costs of applying tick control. Assuming that each standard female tick represents a 10 gram weight loss, the economic damage threshold (standard female ticks/week) is equivalent to the ratio of the producer price of beef (liveweight equivalent): per head cost of dipping (Eqn (3)). To illustrate the application of the threshold methodology, it was assumed that the producer price of beef was Z$1.63/kg (U.S.$0.33/kg) and that tick control cost Z$0.29/hd/dip (U.S.$0.06/hd/dip). This gave a threshold of 18 standard female ticks/head/week. Using tick counts obtained from 20 Brahman cattle held at Mbizi in southeastern Zimbabwe, it was shown that for the 1988 calendar year there were only 32 weeks when the economic damage threshold was met or exceeded. This is substantially less that the 44 dippings per year that have been, until very recently, legally required in Zimbabwe. Sensitivity analysis showed that a 10% rise in the cost of dipping reduced to 23 (a 28% decrease) the number of weeks when tick burdens exceeded the economic damage threshold. By further assuming that an acaricide application and residual effects will cause a 3-5 week interval before the next application may be required, the number of weeks when the tick burden was equal to or greater than the threshold of 18 standard females/week fell to just 9-12 weeks. Three factors may cause an alteration in the economic damage threshold: i) tick burdens may cause damage to the udders; ii) secondary infestations (e.g., screw-worm) may cause economic damage; and iii) nutritional stress of the cattle may reduce the actual average per tick weight loss.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

DNA-ploidy, G2M-fractions and prognosis of stages B and C prostate carcinoma.

Paraffin embedded tissue of 49 stage C and 27 stage B prostate adenocarcinomas was investigated by flow cytometry. All patients were treated by radical prostatectomy with pelvic lymphadenectomy and followed up for 5-10 years. The tumour was separated from the benign tissue to increase the proportion of tumour cells. Ten stage C and seven stage B carcinomas had to be excluded because of poor fixation. Six of the 39 (15%) stage C and 1/20 (5%) stage B carcinomas were aneuploid. Cell cycle analysis was done with correction for sliced nuclei and background subtraction. The threshold between carcinomas with low and with increased ("tetraploid") G2M-fraction was determined by comparing carcinomas with and without tumour progression. Sixty-seven percent of the patients with non-euploid stage C carcinomas and 11% of those with euploid carcinomas suffered from tumour progression (P < 0.01). The respective values for the stage B carcinomas were 67% and 6% (P < 0.01). These results demonstrate the strong prognostic impact of DNA-ploidy and G2M-fractions for each individual patient.

Adult↗
PubMed1988

Osmoregulation of vasopressin secretion and thirst in cyclical oedema.

Osmoregulation of vasopressin release and thirst was studied in the mid-follicular and mid-luteal phases of the menstrual cycle of five patients with cyclical oedema defined by peripheral oedema and weight gain (greater than 3.0 kg) manifest in two consecutive luteal phases. Results are compared to those already obtained in eight healthy women. In the patients, basal plasma osmolality in the mid-luteal phase was significantly lower than in the mid-follicular periods (patients, 283 +/- 1, 287 +/- 1 mOsmol/kg, respectively, mean +/- SEM, P less than 0.05; controls, 282 +/- 1, 286 +/- 1 mOsmol/kg, respectively, P less than 0.05). Plasma osmolality (pOsm) and plasma arginine vasopressin (pAVP) were measured during hypertonic (850 mmol/l) saline infusion in both phases of the cycle; linear regression analyses of these data gave the following mean regression equations, (i) mid-follicular, pAVP = 0.55 (pOsm - 285), r = 0.94 and (ii) mid-luteal, pAVP = 0.42 (pOsm - 281), r = 0.93. The abscissal intercept was significantly different (P less than 0.025). Osmotic threshold for severe thirst onset was lower in the mid-luteal phase compared to the mid-follicular value (296 +/- 1, 299 +/- 1 mOsmol/kg, respectively, P less than 0.01). Basal data and results of thirst onset and theoretical threshold for vasopressin release in response to osmotic stimulation obtained in the patients were similar to healthy control women. We conclude that osmoregulation in cyclical oedema is normal.

Adult↗
PubMed2003

Effects of electrical stimulation on VO2 kinetics and delta efficiency in healthy young men.

OBJECTIVE: To determine the effects of electrical stimulation (ES) on oxygen uptake (VO(2)) kinetics and delta efficiency (DE) during gradual exercise. The hypothesis was that ES would attenuate the VO(2)-workload relation and improve DE. METHODS: Fifteen healthy, untrained men (mean (SD) age 22 (5) years) were selected. Ten were electrostimulated on both quadriceps muscles with a frequency of 45-60 Hz, with 12 seconds of stimulation followed by eight seconds recovery for a total of 30 minutes a day, three days a week for six weeks. The remaining five subjects were assigned to a control group. A standardised exercise test on a cycle ergometer (ramp protocol, workload increases of 20 W/min) was performed by each subject before and after the experimental period. The slope of the VO(2)-power output (W) relation (deltaVO(2)/deltaW) and DE were calculated in each subject at moderate to high intensities (above the ventilatory threshold-that is, from 50-60% to 100% VO(2)max). RESULTS: The mean (SEM) values for deltaVO(2)/deltaW and DE had significantly decreased and increased respectively after the six week ES programme (p<0.05; 9.8 (0.2) v 8.6 (0.5) ml O(2)/W/min respectively and 27.7 (0.9) v 31.5 (1.4)% respectively). CONCLUSIONS: ES could be used as a supplementary tool to improve two of the main determinants of endurance capacity, namely VO(2) kinetics and work efficiency.

Adult↗
PubMed2004

Estimation of the follicle-stimulating hormone (FSH) threshold for initiating the final stages of follicular development in women with elevated FSH levels in the early follicular phase.

OBJECTIVE: To test the hypothesis that the follicle-stimulating hormone (FSH) threshold in patients with elevated FSH levels in the early follicular phase (EFP) is higher than in controls. DESIGN: Pilot study. SETTING: Academic hospital. PATIENT(S): Six patients with elevated EFP FSH (>10 IU/L) and 13 controls. INTERVENTION(S): Treatment with a GnRH agonist in the midluteal phase before IV administration of recombinant FSH was started in an ultra-low-dose step-up protocol. The FSH threshold was determined by the mean of FSH levels of the above threshold value and the below threshold value. MAIN OUTCOME MEASURE(S): Follicle-stimulating hormone threshold, FSH screening value, E(2), number of follicles. RESULT(S): The FSH threshold in the elevated EFP FSH group was 6.75 IU/L and was significantly higher than the FSH threshold of the controls (4.65 IU/L). The FSH screening value on day 3 was 12.0 IU/L in the patient group and 5.0 IU/L in the controls. Estradiol was significantly lower on the day that the largest follicle was 18 mm in the elevated EFP FSH group compared with controls (277 vs. 491 pmol/L, respectively). On the day of hCG administration, the number of smaller (10-13 mm) follicles was equal but the number of larger (>14 mm) follicles was higher in the control group compared with the elevated FSH group. In the control group, the basal FSH levels correlated highly with the FSH threshold levels (r = 0.8), but in the patients with elevated EFP FSH this correlation was absent. CONCLUSION(S): In normal women, basal FSH day 3 values represent the ovarian threshold for FSH. In women with elevated day 3 FSH, the FSH threshold is higher but not as high as basal FSH values. We postulate that the FSH threshold in patients with elevated EFP FSH is higher because of intraovarian factors. Basal FSH overshoots the threshold, probably because of the limited feedback by the ovary.

Chorionic Gonadotropin↗
PubMed1985

Ventilatory response during incremental exercise tests in weight lifters and endurance cyclists.

The effect of a progressively increasing work rate (15 W X min-1) up to exhaustion on the time course of O2 uptake (VO2), ventilation (VE) and heart rate (HR) has been studied in weight lifters (WL) in comparison to endurance cyclists (Cycl) and sedentary controls (Sed). VO2 and VE were measured as average value of 30-s intervals by a semiautomatic open circuit method. VO2max was 2.55 +/- 0.33; 4.29 +/- 0.53 and 2.86 +/- 0.19 l X min-1 in WL, Cycl and Sed respectively. With time and work rate, while VO2 and HR increased linearly, VE changed its slope at two levels. The 1st VE change occurred at a work load corresponding to a mean (+/- SD) VO2 of 1.50 +/- 0.26; 1.93 +/- 0.34; and 1.23 +/- 0.14 l X min-1 in WL, Cycl, and Sed respectively. VO2 values corresponding to the second VE change of slope were 2.18 +/- 0.32 in WL; 3.48 +/- 0.53 in Cycl and 2.17 +/- 0.28 l X min-1 in Sed. The first change of slope might be the consequence of the different readjustment of VO2 on-response and hence of early lactate in the different subjects. The second change seems to be comparable to the conventional anaerobic threshold and is achieved in all subjects when VE vs time slope is 7-10 l X min-1/min of exercise.

Adult↗
PubMed2003

A theoretical study of effects of cytosolic Ca2+ oscillations on activation of glycogen phosphorylase.

Taking into account the Ca(2+)-stimulated degradation of inositol 1,4,5-trisphosphate (IP(3)) by a 3-kinase, we have theoretically explored the effects of both simple and complex Ca(2+) oscillations on the regulation of a phosphorylation-dephosphorylation cycle process involved in glycogen degradation by glycogen phosphorylase a-form, respectively. For the case of simple Ca(2+) oscillations, the roles of cytosolic Ca(2+) oscillations in the regulation of active phosphorylase depend upon the maximum rate of IP(3) degradation by the 3-kinase, V(M5). In particular, the smaller the values of V(M5) are, the lower the effective Ca(2+) threshold for the activation of glycogen phosphorylase will be. For the case of complex Ca(2+) oscillations, the average level of fraction of active phosphorylase is nearly independent from the level of stimulation increasing in the bursting oscillatory domain. Both simple and complex Ca(2+) oscillations can contribute to increase the efficiency and specificity of cellular signalling, and some theoretical results of activation of glycogen phosphorylase regulated by Ca(2+) oscillations are close to the experimental results for gene expression in lymphocytes.

Calcium Signaling↗