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[Evaluation of the secretory activity of the adrenal cortex and gonads in women with epilepsy. II. Urinary excretion of estrogen fractions and alpha and beta pregnanediol during the 2 days preceding menstrual bleeding].

In 32 women with epileptic seizures related in time to the premenstrual phase (group A) and 31 women with seizures unrelated to this phase (group B) oestrone oestradiol and oestriol and progesterone metabolites (alpha and beta-pregnanediol) were determined in 24-hour urine. The investigations were carried out during 2 days preceding the onset of menstrual bleeding usually during three successive cycles. A significant reduction was observed in the amounts of all three oestrogen fractions in relation to normal values on both days (without any significant difference between the groups). Women with epilepsy excreted 56-60% less oestrogens than healthy women. Similarly the levels of alpha and beta-pregnanediol were significantly below the accepted normal range. The obtained results are insufficient for accepting the role of oestrogens in the development of lowered convulsive threshold on the days preceding menstrual bleeding. On the other hand, it may be concluded that progesterone deficiency may have an effect on the appearance of greater readiness to seizures before menstruation in epileptic women.

Adult↗

Improvement in exercise tolerance and spirometric values in stable chronic obstructive pulmonary disease patients after an individualized outpatient rehabilitation programme.

OBJECTIVE: We sought to determine whether patients with stable chronic obstructive pulmonary disease (COPD) whose exercise performance is mainly limited by dyspnoea are able to improve their exercise tolerance after rehabilitation with an individualized programme based on aerobic training at the ventilatory threshold (VT) level. PATIENTS AND EXPERIMENTAL DESIGN: Thirteen stable and moderate to severe COPD patients took part in an outpatient rehabilitation programme lasting 4 months. This individualized programme consisted of exercise training (general training on cycle and upper-limb training by rowing at the heart rate corresponding to VT) together with provision of adequate calorie and protein support. RESULTS: Lung function test after rehabilitation revealed significant increases in FVC (82.9 vs 69.2 % pred) and FEV1 (47.2 vs 39.7 % pred), although FEV1/FVC were unchanged (44.8 vs 46.8%). Incremental exercise test performed on cycle revealed significant increases in time, work rate (82.0 vs 63.2 W), peak VO2 (14.6 vs 10.7 ml.kg-1.min-1), peak VO2 (840 vs 701 ml.min-1), peak VT (1309 vs 980 ml), and O2-pulse (8.3 vs 6.7). However, exercise tests were always symptom-limited by dyspnoea. CONCLUSIONS: We conclude that this individualized outpatient rehabilitation programme is able to improve exercise tolerance in stab le COPD patients affected by dyspnoea during exercise, through an apparent reconditioning of both skeletal and respiratory muscles and improved gas exchange during exercise, thus reducing the ratio of dead space to tidal volume. In consequence, patients whose exercise capacity is so reduced that they cannot develop significant lactic acidosis may reduce the ventilatory cost for exercise through this individualized therapy.

Aged↗

Effects of gender and gonadal hormones on nociceptive responses to intraplantar carrageenan in the rat.

The effects of gender and gonadal hormones on nociceptive responses to intraplantar carrageenan in the rat were investigated. A plantar analgesic meter was used to measure carrageenan-induced changes in paw withdrawal latency (PWL) values, and von Frey monofilaments were used to assess changes in paw withdrawal threshold (PWT) values in response to tactile-evoked (mechanical) stimuli. The data revealed that PWL values were significantly greater in gonadally-intact females than in gonadally-intact males, and this response was abolished by surgical gonadectomies. Gonadally-intact as well as gonadectomized male and female rats also exhibited significant carrageenan-induced decreases in PWT, but neither sex- nor gonadectomy-related differences were detected in the development of mechanical allodynia. These findings demonstrate that intraplantar carrageenan induces nociceptive behaviors in rats that are differentially affected by sex and gonadal hormones.

Animals↗

Cell cycle kinetics of regenerating urothelial cells of the rat urinary bladder after partial cystectomy.

The cell cycle kinetics of bladder urothelial cells regenerating after partial cystectomy were investigated in 96 female Wistar rats using the percentage labelled mitoses method. In the area of resection a mean cell cycle time (TC) of 15 h was determined. The DNA synthesis phase (TS) lasted 6 h and the premitotic-postsynthetic phase together with the mitosis phase (TG2 + M) 1.5 h, thus giving a presynthetic-postmiotic phase (TG1) of 7.5 h. Similar values were found for the urothelial cells in the stump: the mean cycle time measured 14 h, the TS-phase 6 h, the TG6 + M-phase 2 h and the TG1-phase 6 h. These data are discussed with respect to known cell cycle parameters of bladder urothelium regenerating in response to cytotoxic agents and of neoplastic urothelial cells. The reported findings provide a basis for further investigations using weak carcinogens and threshold doses of potent carcinogens to test the working hypothesis that stimulation of proliferation following partial cystectomy is capable of initiating, accelerating and/or potentiating carcinogenic cell transformation in the urinary bladder.

Animals↗

Time-dependent anesthetic and anticonvulsant activities of alphaxalone in Syrian hamsters.

To assess whether the anesthetic and anticonvulsant activities of alphaxalone display diurnal variability, groups of Syrian hamsters were studied at 4 h-intervals during a 24 h-cycle. The administration of alphaxalone (5 mg/kg) brought about a greater anesthetic activity (loss of righting reflex) at the middle of the photophase. When assessed in hamsters injected with 3-mercaptopropionic acid, alphaxalone displayed maximal anticonvulsant activity at the 4th of darkness. Evaluation of the time needed for first convulsive response indicated that alphaxalone did not show time-dependent effects, while in control hamsters seizure threshold was low during daylight and attained maximal values at night, showing a peak in seizure threshold at light-dark transition.

3-Mercaptopropionic Acid↗

Estimating tsetse population parameters: application of a mathematical model with density-dependence.

A density-dependent model is used to describe the dynamics of an open population of tsetse flies (Diptera: Glossinidae). Immigration (or emigration) takes place when the total population is below (or above) a biologically determined threshold value. The population is also subjected to birth and death rates, as well as to the risk of being trapped (continuously or intermittently). During trapping the population decreases toward a 'low' equilibrium population and when trapping ceases the population starts recovering and increases toward a 'high' equilibrium. The model is fitted using data collected on trapped flies in four experiments. The first one was conducted with 'intermittent trapping' (i.e. several trapping-recovery cycles) on Glossina fuscipes fuscipes Newstead in the Central African Republic (Bangui area). In the other experiments, trapping data on Glossina palpalis palpalis (Robineau-Desvoidy) was collected in 'aggregate' form over several days at a time. Two of these were in Congo-Brazzaville (Bouenza area) and one in the Ivory Coast (Vavoua focus). Estimates are derived for the low and high equilibrium values as well as the trapping rate. The estimated effect of sustained trapping is to reduce the population to low equilibrium values that are 85-87% lower than the levels without trapping. The effects of the natural intrinsic growth and of the migration flows cannot be estimated separately because in the model they are mathematically indistinguishable.

Animal Migration↗

Core temperature "null zone".

An experimental protocol was designed to investigate whether human core temperature is regulated at a "set point" or whether there is a neutral zone between the core thresholds for shivering thermogenesis and sweating. Nine male subjects exercised on an underwater cycle ergometer at a work rate equivalent to 50% of their maximum work rate. Throughout an initial 2-min rest period, the 20-min exercise protocol, and the 100-min recovery period, subjects remained immersed to the chin in water maintained at 28 degrees C. On completion of the exercise, the rate of forehead sweating (Esw) decayed from a mean peak value of 7.7 +/- 4.2 (SD) to 0.6 +/- 0.3 g.m-2.min-1, which corresponds to the rate of passive transpiration, at core temperatures of 37.42 +/- 0.29 and 37.39 +/- 0.48 degrees C, as measured in the esophagus (Tes) and rectum (Tre), respectively. Oxygen uptake (VO2) decreased rapidly from an exercising level of 2.11 +/- 0.25 to 0.46 +/- 0.09 l/min within 4 min of the recovery period. Thereafter, VO2 remained stable for approximately 20 min, eventually increased with progressive cooling of the core region, and was elevated above the median resting values determined between 15 and 20 min at Tes = 36.84 +/- 0.38 degrees C and Tre = 36.80 +/- 0.39 degrees C. These results indicate that the core temperatures at which sweating ceases and shivering commences are significantly different (P less than 0.001) regardless of whether core temperature is measured within the esophagus or rectum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Antagonist protocols: residual LH levels and the value of exogenous LH supplementation].

When administered in the late follicular phase to prevent any LH surge, GnRH antagonists induce a sharp decrease in serum LH levels that may be detrimental for assisted reproductive technology cycle outcome. This decrease in LH levels is dose-dependant. Supplementation with recombinant LH when introducing GnRH antagonist leads to significant changes in E2 secretion. This is consistent with a key role of LH to ensure adequate steroidogenesis. This also indicates that a single dose of GnRH antagonist is able to decrease bioactive LH below a minimal threshold for optimal steroidogenesis. However, supplementation with rLH does not modify the number of retrieved oocytes, obtained embryos and the pregnancy rate. This is in line with the concept that folliculogenesis is mainly dependent on FSH and that the role of LH and E2 is not primordial. Indeed, the findings of our prospective randomized study do not support a systematic supplementation with rLH when introducing antagonist. However, further studies are necessary to determine whether a specific sub group of patients characterized by a low E2/oocyte ratio could benefit from rLH supplementation.

Adult↗

The relationship of the heart rate deflection point to the ventilatory threshold in trained cyclists.

The purpose of this study was to assess the relationship of the heart rate deflection point (HRDP) to the ventilatory threshold (VT) in trained cyclists. Twenty-one endurance-trained cyclists (mean +/- SD: Vo(2)max = 67.6 +/- 4.7 ml x kg x min(-1)) completed a maximal cycle ergometer test of volitional fatigue using a ramped protocol. Ventilatory variables (Ve, Vo(2), Vco(2)) and power were measured online with averages reported every 20 seconds. Heart rate (HR) was recorded every 20 seconds using a Polar monitor. VT was calculated using the excess CO(2) elimination curve. The first derivative of a logistic growth curve fit to the HR-power data produced the HRDP. No significant differences (p > 0.01) existed between HR values at HRDP (171.7 +/- 9.6 b x min(-1)) and VT (169.8 +/- 9.9 b x min(-1)) or between Vo(2) values at HRDP (53.6 +/- 4.2 ml x kg x min(-1)) and VT (52.2 +/- 4.8 ml x kg x min(-1)). But power values at HRDP (318.7 +/- 30.7 W) were significantly different (p < 0.01) from those at VT (334.8 +/- 36.7 W). There were significant relationships between HRDP and VT for the physiological variables of HR (r = 0.92, p < 0.001), Vo(2) (r = 0.72, p < 0.001), and power (r = 0.77, p < 0.001). These findings indicate that HR and Vo(2) at HRDP are not significantly different from the values at VT in trained cyclists. HR values derived from HRDP may be used to set parameters for training intensity. Variability in the speed/power-HRDP relationship across detrained/trained states may be used to evaluate training programs.

Adult↗

Decision analysis of hematopoietic growth factor use in patients receiving cancer chemotherapy.

BACKGROUND: Hematopoietic growth factors (HGFs) have been shown to reduce the incidence of neutropenia and fever in patients receiving cancer chemotherapy. PURPOSE: This cost analysis was designed to determine the conditions in which use of HGFs in patients receiving cancer chemotherapy is cost-effective. METHODS: We used a standard model based on decision theory; the model assumes that all patients experiencing neutropenia and fever will be hospitalized and treated with intravenous antibiotics. Data from a prospective, randomized clinical trial of granulocyte colony-stimulating factor in small-cell lung cancer treated with combination chemotherapy were used to determine baseline probabilities for control hospitalization risk and survival; proportional hospitalization risk with prophylactic HGF; and median durations of hospitalization and prophylactic HGF use. The model was analyzed by one-way and multivariate sensitivity analyses, with estimation of threshold values at which the expected cost is the same for either of two treatment options. One or more of the specific costs and durations and the probability for each group of threshold curves were varied in a sensitivity analysis that generated variable thresholds. Use of Monte Carlo analysis based on the available distributions of the main variables provided 90% confidence limits and an inference method for comparing decision options. RESULTS: The expected excess cost per treatment cycle, based on hospitalization for neutropenic fever and/or HGF administration, was $5500 for no HGF, $4750 for prophylactic HGF, and $6875 for therapeutic HGF. Sensitivity analysis provided the following thresholds for no HGF versus prophylactic HGF: control risk of hospitalization, 0.40; risk of hospitalization with HGF as a proportion of control, 0.64; total daily cost of hospitalization, $727; total daily cost of HGF, $344; duration of hospitalization, 7.3 days; and duration of HGF use, 11.0 days. Multivariate analysis revealed that conditions favoring the use of HGF on a cost basis become greater (a) as risk of hospitalization, total daily hospital cost, and duration of hospitalization increase and (b) as the proportional risk of hospitalization with HGF, daily cost of HGF, and duration of HGF treatment decrease. CONCLUSIONS: The major determinants of total excess cost were the control risk of hospitalization, the proportional reduction in risk with HGF, and the average daily hospital cost. IMPLICATIONS: Use of HGFs should be based on the risk of hospitalization for neutropenic fever and consideration of the patient population and institutional costs.

Colony-Stimulating Factors↗

Taq DNA polymerase slippage mutation rates measured by PCR and quasi-likelihood analysis: (CA/GT)n and (A/T)n microsatellites.

During microsatellite polymerase chain reaction (PCR), insertion-deletion mutations produce stutter products differing from the original template by multiples of the repeat unit length. We analyzed the PCR slippage products of (CA)n and (A)n tracts cloned in a pUC18 vector. Repeat numbers varied from two to 14 (CA)n and four to 12 (A)n. Data was generated on approximately 10 single molecules for each clone type using two rounds of nested PCR. The size and peak areas of the products were obtained by capillary electrophoresis. A quasi- likelihood approach to the analysis of the data estimated the mutation rate/repeat/PCR cycle. The rate for (CA)n tracts was 3.6 x 10(-3) with contractions 14 times greater than expansions. For (A)n tracts the rate was 1.5 x 10(-2) and contractions outnumbered expansions by 5-fold. The threshold for detecting 'stutter' products was computed to be four repeats for (CA)n and eight repeats for (A)n or approximately 8 bp in both cases. A comparison was made between the computationally and experimentally derived threshold values. The threshold and expansion to contraction ratios are explained on the basis of the active site structure of Taq DNA polymerase and models of the energetics of slippage events, respectively.

Base Sequence↗

Timing of FSH administration for ovarian stimulation in normo-ovulatory women: comparison of an early or a mid follicular phase initiation of a short-term treatment.

BACKGROUND: In normo-ovulatory infertile women undergoing mild ovarian stimulation out of IVF, FSH stimulation regimen must be carefully adjusted to control the number of recruited follicles and to prevent multiple pregnancies. The aim of this prospective study was to assess the effect of the timing of FSH administration (fixed dose and duration) on the number of large follicles. METHODS: Women were prospectively randomized by means of sealed envelopes to receive daily 112.5 IU recombinant FSH (rFSH), either from cycle day (CD) 2-6 (Group A) or from CD 7-11 (Group B). Hormonal measurements and follicular ultrasound assessments were performed on CD 2, 7 and 12. RESULTS: On CD 12, the development rate of exactly two follicles >or=14 mm in diameter was significantly lower in Group A than in Group B (4% of women versus 42%, P = 0.002). Although the pattern of serum estradiol (E(2)) concentrations in Group A displayed a plateau from CD 7, the cancellation rate for overstimulation (more than three follicles >or=14 mm in diameter) was significantly increased (P = 0.009). CONCLUSIONS: Preventing the closure of the FSH window by mid to late follicular phase FSH administration better fulfils the objective of obtaining a limited number of large follicles than surpassing the FSH threshold by an early administration.

Estradiol↗

Effects of flecainide acetate on ventricular tachyarrhythmia and fibrillation in dogs with recent myocardial infarction.

The antiarrhythmic and antifibrillatory actions of the class IC antiarrhythmic agent flecainide acetate were examined in urethane-anesthetized dogs with recent myocardial infarction. The intravenous administration of flecainide in a loading dose of 1.0 mg/kg (n = 7) or 2.0 mg/kg (n = 6), followed by a maintenance infusion of 1.0 mg/kg/h to achieve plasma drug concentrations considered clinically therapeutic, failed to significantly elevate the electrical threshold current required to provoke ventricular fibrillation at infarct zone, border zone and non-infarct zone stimulation sites in postinfarction dogs. In 8 dogs which responded to baseline programmed stimulation with inducible sustained ventricular tachycardia, flecainide administered as 1.0 or 2.0 mg/kg loading doses followed by a 1.0 mg/kg/h maintenance infusion failed to prevent ventricular tachycardia initiation in any animal tested, although the post-treatment ventricular tachycardia cycle lengths were prolonged compared to baseline values (pre: 178 +/- 11 ms vs post: 202 +/- 17 ms, p less than 0.05). Flecainide administration apparently facilitated the induction of newly sustained ventricular tachycardia in 3 previously noninducible postinfarction dogs. The development of acute posterolateral ischemia at a site remote from previous anterior myocardial infarction resulted in the development of ventricular fibrillation in 4 of 11 (36%) saline-treated postinfarction dogs vs a cumulative 10 of 12 (83%) flecainide-treated, baseline noninducible postinfarction dogs (p less than 0.05 vs saline-treated). The incidence of sudden ischemic ventricular fibrillation was 7 of 7 (100%) among flecainide-treated baseline inducible postinfarction dogs. These data suggest that flecainide acetate may have only limited efficacy in preventing ventricular tachycardia or ventricular fibrillation soon after myocardial infarction.

Animals↗

The importance of the elastic and plastic components of strain in tensile and compressive fatigue of human cortical bone in relation to orthopaedic biomechanics.

The longevity, success, or failure of an orthopaedic implant is dependent on its osseointegration especially within the initial six months of the initial surgery. The development of strains plays a crucial role in both bone modelling and remodelling. For remodelling, in particular, strains of substantial values are required to activate the osteoblastic and osteoclastic activity for the osseointegration of the implant. Bone, however, is subject to "damage" when strain levels exceed a certain threshold level. Damage is manifested in the form of microcracks; it is linked to increased elastic strain amplitudes and is accompanied by the development of "plastic" (irrecoverable, residual) strains. Such strains increase the likelihood for the implant to subside or loosen. The present study examines the rates (per cycle) by which these two components of strain (elastic and "plastic") develop during fatigue cycling in two loading modes, tension and compression. The results of this study show that these strain rates depend on the applied stress in both loading modes. It also shows that elastic and plastic strain rates can be linked to each other through simple power law relationships so that one can calculate or predict the latter from the former and vice versa. We anticipate that such basic bone biomechanics data would be of great benefit to both clinicians and bioengineers working in the field of FEA modelling applications and orthopaedic implant surgery.

Aged↗

Exercise responses in patients with an enzyme deficiency in the mitochondrial respiratory chain.

Responses to exercise were obtained in six patients with a biochemically diagnosed enzyme deficiency at the level of NADH-CoQ reductase. The responses were compared with those of a control group, consisting of fourteen patients with inexplicable dyspnoea or muscle pain during exercise, for which no firm diagnosis could be established and of which the exercise responses were in the normal range. Metabolic, ventilatory and cardiological variables such as oxygen uptake (VO2), minute ventilation (VE), respiratory exchange ratio (R), heart rate (HR) and difference in blood lactate or base-excess (BE) between rest and maximal workload were measured during cycle ergometry from samples obtained in the last minutes of four minute periods, in which the load increased stepwise by 30 W per four minutes. The threshold of lactate metabolism (Tlact) was assumed to be equal to the threshold determined both by the VO2 at which the VE versus VO2 response started to deviate from a straight line and the ventilatory equivalent for oxygen (VE/VO2) showed a minimum (Tvent), Tvent was estimated from the mean of these values, obtained by linear and parabolic regression analysis respectively. In the patient group, mean values for symptom limited maximal VO2 (VO2,max,sl; % of VO2,max,ref), Tvent (% of VO2,max,ref) and R at maximal workload were 43, 17 and 1.23 against 85, 47 and 1.06 for the same variables in the control group, respectively. The differences were highly significant (p less than 0.001; p less than 0.005 for mean R difference). Mean maximal HR and mean change in blood lactate or BE were not significantly different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Regulation of activity of cardiac vagal motoneurons.

The discharge patterns of the axons of cardiac vagal motoneurons responding to carotid baroreceptor activation are described. Step and sinusoidal pressure waves were applied to the right isolated perfused carotid sinus in the cat. Other major baroreceptor inputs were eliminated by nerve section. The threshold for activation of cardiac vagal efferent fibers fell into two groups. The mean threshold for one group of 24 fibers was 117 mm Hg and for the other higher threshold group (3 fibers) was 192 mmHg. The peak frequency of discharge in response to a step rise in carotid pressure was proportional to the value of the pressure but seldom exceeded 35/sec even at high carotid sinus pressure. Adapted frequency during the step rise in pressure was also directly related to the carotid sinus pressure and seldom exceeded 6/sec. The fibers responded to sinusoidal pressure waves with a decrease in the number of spikes per cycle as the sinusoidal frequency increased. The average discharge frequency over 2 minutes remains constant over sinusoidal pressures of 0.03 Hz to 4 Hz. These characteristics of the vagal motoneurons are discussed in relationship to known properties of the baroreceptor afferents, which make up the afferent limb of this reflex pathway.

Action Potentials↗

Ventilatory and gas-exchange responses to incremental exercise performed with reduced muscle glycogen content.

This study examined the relationship between minute ventilation (VE), CO2 production (VCO2), and blood lactate concentration ([La-]) during incremental exercise performed with reduced muscle glycogen stores. Nine untrained female subjects (25.3+/-4.2 year) performed incremental cycling in a normal glycogen (NG) state and under conditions of reduced muscle glycogen (RG) content. To reduce muscle glycogen stores, subjects cycled to exhaustion (124+/-33 min) at a power output corresponding to their gas-exchange anaerobic threshold. Peak oxygen uptake (VO2peak) was unchanged with glycogen reduction, even though subjects achieved a significantly lower maximal power output in the RG state (p<0.05). Peak blood [La-] decreased significantly by 37% in the RG state (p<0.001). At any percentage of VO2peak, O2 uptake and VE were similar for both treatment conditions, whereas VCO2 and respiratory exchange ratio values were lower during the RG trial than under NG conditions. Therefore, VE/VCO2 tended to be higher and end-tidal CO2 partial pressure tended to be lower during exercise performed in the RG state. VE was significantly correlated with VCO2 under both treatment conditions (NG: r=0.99, p<0.01; RG: r=0.99, p<0.01). However, the slope of the VE-VCO2 relationship was significantly elevated during the RG trial (p<0.01). VE during exercise was similar under both treatment conditions, even though VCO2 and blood [La-] were lower during the RG trial compared to the NG trial. This suggests that factors other than CO2 delivery to the lung and metabolic acidosis play an important role in regulating VE during exercise.

Adult↗

The use of dynamic phantoms in interventional radiology.

The authors have constructed a 2D motor-controlled test object phantom holder to simulate clinical situations in which patient movement could be a cause of image degradation. The PAtient MOvement SImulation Test Object (PAMOSITO) has been constructed with modular parts to use different mobile test objects and static structures. The system allows the programming of different cycles of movement along two axes. PAMOSITO has been used in X ray equipment dedicated to interventional radiology. Those systems usually allow for different values for frame rate, pulse width or weighted frame averaging methods. The influence of selecting different values of the parameters, patient movement and its relation to patient dose and image quality has been studied. Image blurring due to motion has been evaluated with Leeds test objects TO.10 and 18FG. Spatial resolution limits and the threshold contrast detail detectability performance have been studied.

Absorptiometry, Photon↗