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PubMed2004

Prediction of pregnancy by intrauterine insemination using CASA estimates and strict criteria in patients with male factor infertility.

This study was performed to predict pregnancy by intrauterine insemination (IUI) using computer-aided sperm analysis (CASA) estimates and strict criteria in patients with male factor infertility. IUI was performed in 682 cycles on 160 male factor infertile patients. Semen examinations were carried out by CASA and strict criteria before and after sperm preparation using continuous-step density gradient centrifugation. Receiver operating characteristics (ROC) curves were constructed for assessment of the effectiveness of each individual parameter in predicting pregnancy by IUI. A clinically acceptable threshold was calculated when sensitivity plus specificity were maximum. The average cycle of IUI performed was 4.3 +/- 2.4. Pregnancy rate per cycle and per patient were 7.2% (49/682) and 28.1% (45/160), respectively. Using ROC curve, it was shown that normal sperm morphology assessed by the strict criteria before sperm separation and five parameters after sperm separation including rapid, progressive motility, average path velocity (VAP), curvilinear velocity (VCL), and straight line velocity (VSL) were able to predict pregnancy by IUI. Correlation between sperm parameters and pregnancy outcome was examined by the logistic regression model. In a multivariate analysis normal morphology before sperm separation >or=15.5% [odds ratio (OR) = 2.2, p = 0.02], rapid after sperm separation >or=25.5% [OR = 3.9, p = 0.029], and VCL after sperm separation >or=102.65 microm/sec [OR = 3.2, p = 0.002] were the parameters of predictive value for pregnancy outcome. Adjustment of the model for female age, female infertility factors, and the methods of ovulation induction did not change this finding, and the final model still had the same covariates. Pregnancy rates per cycle according to the number (0, 1, 2 and 3) of variables satisfied with the three parameters were 0% (0/110), 1.6% (3/183), 9.7% (21/217) and 15.1% (23/151), respectively. Three semen parameters including normal morphology before sperm separation, rapid and VCL after sperm separation were identified as predictors of pregnancy by IUI. These variables would be helpful when counselling patients before they make the decision to proceed with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)-ET.

Adult↗
PubMedDate not supplied

Automatic 3D vascular tree construction in CT angiography.

This study presents an automatic method for 3D reconstruction of vascular trees using computed-tomography angiographic (CTA) images. The program starts with the CTA slices, performs a sequential procedure of 3D image formation, preprocessing, segmentation, thinning, skeleton pruning and tree construction. It ends with vascular trees along with quantitative data about the trees such as values of diameter, length and bifurcation angles. All the involved algorithms are presented with the emphasis given to the skeleton pruning and tree construction algorithms. The skeletons obtained using a 3D thinning algorithm may contain cycles, spurs, isolated sticks, and non-unit-width parts, which hinder tree construction. As a solution to this problem, a skeleton pruning and tree construction algorithm is proposed. At each stage of the automatic procedure, 3D rendering is provided for visual inspection of the computed results. In the final output, the constructed vascular trees are visualized by rendering the 3D trees and the 3D binary image together in a transparent display mode. The program is carried out in a fully automatic fashion, with a few default settings. Occasionally, user intervention is needed at the 3D segmentation stage to impose an appropriate threshold when the automatic 3D segmentation is obviously sub-optimal for vessel delineation. Experimental demonstrations on both coronary artery phantom and a cast of coronary artery tree of a swine animal model are provided.

Angiography↗
PubMed1997

On the Mechanism of Reinitiation of Endogenous Crassulacean Acid Metabolism Rhythm by Temperature Changes.

Under continuous light the endogenous Crassulacean acid metabolism (CAM) rhythm of Kalanchoe daigremontiana Hamet et Perrier de la Bathie disappears at high (>29.0[deg]C) or low (<8.0[deg]C) temperatures. We investigated the reinitiation of rhythmicity when temperature was reduced from above the upper and increased from below the lower threshold level via measurements of (a) short-term changes in carbon-isotope discrimination to illustrate shifts between C3 and C4 carboxylation in vivo, and (b) the malate sensitivity of phosphoenolpyruvate carboxylase (PEPC) in vitro. When the net CO2-exchange rhythm disappears at both temperatures, the instantaneous discrimination indicates low PEPC activity. Leaf malate concentration and osmolarity attain high and low values at low and high temperatures, respectively. After small temperature increases or reductions from the low and high temperatures, respectively, the rhythm is reinitiated, with phases shifted by 180[deg] relative to each other. This can be related to the contrasting low and high leaf malate concentrations due to direct inhibition of PEPC and possibly also of the phosphorylation of PEPC by malate. The experimental results were satisfactorily simulated by a mathematical CAM-cycle model, with temperature acting only on the passive efflux of malate from the vacuole. We stress the important role of the tonoplast in malate compartmentation and of malate itself for the reinitiation and generation of endogenous CAM rhythmicity.

Journal Article↗
PubMed2005

Specificity of VO2MAX and the ventilatory threshold in free swimming and cycle ergometry: comparison between triathletes and swimmers.

OBJECTIVES: To compare maximal heart rate (HRmax), maximal oxygen consumption (VO2MAX), and the ventilatory threshold (VT; %VO2MAX) during cycle ergometry and free swimming between swimmers and triathletes. METHODS: Nine swimmers and ten triathletes completed an incremental swimming and cycling test to exhaustion. Whole body metabolic responses were determined in each test. RESULTS: The swimmers exhibited a significantly higher VO2MAX in swimming than in cycling (58.4 (5.6) v 51.3 (5.1) ml/kg/min), whereas the opposite was found in the triathletes (53.0 (6.7) v 68.2 (6.8) ml/kg/min). HRmax was significantly different in the maximal cycling and swimming tests for the triathletes (188.6 (7.5) v 174.8 (9.0) beats/min). In the maximal swimming test, HRmax was significantly higher in the swimmers than in the triathletes (174.8 (9.0) v 184.6 (9.7) beats/min). No significant differences were found for VT measured in swimming and cycling in the triathletes and swimmers. CONCLUSION: This study confirms that the exercise testing mode affects the VO2MAX value, and that swimmers have very specific training adaptations even compared with triathletes. This may be a function of acute physiological responses combined with the specialist training status of the different athletes influencing maximal cardiac output or oxygen extraction. In contrast, the different training regimens do not seem to influence the VT, as this variable did not differ between the two testing modes in either group.

Adolescent↗
PubMed1998

Regional differences in the effect of exercise intensity on thermoregulatory sweating and cutaneous vasodilation.

To investigate regional body differences in the effect of exercise intensity on the thermoregulatory sweating response, nine healthy male subjects (23.2 +/- 0.4 year) cycled at 35, 50 and 65% of their maximal O2 uptake (VO2max) for 30 min at an ambient temperature of 28.3 +/- 0.2 degrees C and a relative humidity of 42.6 +/- 2.4%. Local sweating rate (msw) on the forehead, chest, back, forearm and thigh increased significantly with increases in the exercise intensity from 35 to 50% VO2max and from 50 to 65% VO2max (P < 0.05). The mean values for the density of activated sweat glands (ASG) at 50 and 65% VO2max at the five sites were significantly greater than at 35% VO2max. The mean value of the sweat output per gland (SGO) also increased significantly with the increase in exercise intensity (P < 0.05). The patterns of changes in ASG and SGO with an increase in exercise intensity differed from one region of the body to another. Although esophageal temperature (Tes) threshold for the onset of sweating at each site was not altered by exercise intensity, the sensitivity of the sweating response on the forehead increased significantly from 35 to 50 and 65% VO2max (P < 0.05). The threshold for cutaneous vasodilation tend to increase with exercise intensity, although the exercise intensity did not affect the sensitivity (the slope in the relationship Tes vs. percentage of the maximal skin blood flow) at each site. Tes threshold for cutaneous vasodilation on the forearm was significantly higher at 65% VO2max than at either 35 or 50% VO2max, but this was not observed at the other sites, such as on the forehead and chest. These results suggest that the increase in msw seen with an increasing intensity of exercise depends first on ASG, and then on SGO, and the dependence of ASG and SGO on the increase in msw differs for different body sites. In addition, there are regional differences in the Tes threshold for vasodilation in response to an increase in exercise intensity.

Adult↗
PubMed2004

Effect of exercise intensity on relationship between VO2max and cardiac output.

PURPOSE: The purpose of this study was to determine whether the maximal oxygen uptake (VO2max) is attained with the same central and peripheral factors according to the exercise intensity. METHODS: Nine well-trained males performed an incremental exercise test on a cycle ergometer to determine the maximal power associated with VO2max (pVO2max) and maximal cardiac output (Qmax). Two days later, they performed two continuous cycling exercises at 100% (tlim100 = 5 min 12 s +/- 2 min 25 s) and at an intermediate work rate between the lactate threshold and pVO2max (tlimDelta50 +/- 12 min 6 s +/- 3 min 5 s). Heart rate and stroke volume (SV) were measured (by impedance) continuously during all tests. Cardiac output (Q) and arterial-venous O2 difference (a-vO2 diff) were calculated using standard equations. RESULTS: Repeated measures ANOVA indicated that: 1) maximal heart rate, VE, blood lactate, and VO2 (VO2max) were not different between the three exercises but Q was lower in tlimDelta50 than in the incremental test (24.4 +/- 3.6 L x min(-1) vs 28.4 +/- 4.1 L x min(-1); P < 0.05) due to a lower SV (143 +/- 27 mL x beat(-1) vs 179 +/- 34 mL x beat(-1); P < 0.05), and 2) maximal values of a-vO2 diff were not significantly different between all the exercise protocols but reduced later in tlimDelta50 compared with tlim100 (6 min 58 s +/- 4 min 29 s vs 3 min 6 s +/- 1 min 3 s, P = 0.05). This reduction in a-vO2 diff was correlated with the arterial oxygen desaturation (SaO2 = -15.3 +/- 3.9%) in tlimDelta50 (r = -0.74, P = 0.05). CONCLUSION: VO2max was not attained with the same central and peripheral factors in exhaustive exercises, and tlimDelta50 did not elicit the maximal Q. This might be taken into account if the training aim is to enhance the central factors of VO2max using exercise intensities eliciting VO2max but not necessarily Qmax.

Adult↗
PubMed2002

Monitoring of peripheral blood CD34+ cell counts on the first day of apheresis is highly predictive for efficient CD34+ cell yield.

The purpose of this study was to evaluate the correlation of preleukapheresis circulating CD 34+ cells/micro L, white blood cells (WBC), and platelet counts on the first day of apheresis with the yield of collected CD 34+ cell counts in 40 patients with hematological malignancies (n = 29) and solid tumors (n = 11). The median numbers of apheresis cycles, numbers of CD 34+ cells, peripheral blood (PB) mononuclear cells, and total nucleated cells collected were 2 (range, 1-4), 5.5 x 106/kg (range, 0.05-33.78), 2.59 x 108/kg (range, 0.04-20.68), and 7.36 x 108/kg (range, 0.15-28.08), respectively. There was a strong correlation between the number of preleukapheresis circulating CD 34+ cells/micro L and the yield of collected CD 34+ cells per kilogram (r = 0.962, p < 0.001). The threshold levels of PB C 34+ cell/micro L to obtain > or =1 x 106/kg and > or =2.5 x 106/kg CD 34+ cell in one collection were 12/micro L and 34/ micro L, respectively. Fifteen of 17 (88%) patients who had > or =34 CD 34+ cells/ micro L in the PB before collection reached the level of > or =2.5 x 106/kg in a single apheresis. Despite a low r value, WBC and platelet counts on the first day of apheresis also correlated with the yield of collected daily CD 34+ cells per kilogram (r = 0.482, p < 0.01 and r = 0.496 p < 0.01, respectively). These data suggest that preleukapheresis circulating CD 34+ cells/ micro L correlated significantly better with the yield of collected CD 34+ cells than WBC and platelet counts on the first day of apheresis. Using a value of 34/micro L preleukapheresis circulating CD 34+ cells as a guide for the timing of peripheral blood stem cells collections can be time saving and cost-effective.

Adolescent↗
PubMed1981

Effect of oral propranolol on the anerobic threshold and maximum exercise performance in normal man.

The effect of propranolol on the anaerobic threshold was studied in six healthy male volunteers. The subjects exercised on a cycle ergometer in a progressive exercise test to exhaustion with propranolol or no drug. Power output was increased by 30 W ever 2 min. Propranolol caused a significant reduction of heart rate by 20-45 beats per minute at all power outputs. In light and moderate exercise, no differences in oxygen uptake, ventilation, or blood lactate were observed in the propranolol and no-drug tests. The anaerobic threshold was not different between the no-drug (2.32 +/- 0.19 L O2/min, mean +/J- SD) and the propranolol (2.83 +/- 0.27 L O2/min) test; however, the heart rate at the anaerobic threshold was significantly lower in the propranolol (143 +/- 13 beats per minute) than the no-drug (187 +/- 9 beats per minute) tests. Above the anaerobic threshold, oxygen uptake was similar at a given power output but it reached a lower peak value (p less than 0.02) in the propranolol (3.16 +/- 0.16 L O2/min) versus the no-drug (3.64 +/- 0.39 L O2/min) tests. It was concluded that propranolol caused no change in anaerobic threshold in this specific progressive exercise protocol. The results suggest that a training intensity for endurance exercise bases on the anaerobic threshold does not need to be modified for subjects on propranolol medication.

Adult↗
PubMed1982

Effect of ramp slope on determination of aerobic parameters from the ramp exercise test.

The effect of ramp slope on determination of aerobic parameters from the ramp exercise test. Med. Sci. Sports Exercise, Vol. 14, No. 5, pp. 339-343, 1982. We have previously demonstrated that the four parameters of aerobic function (maximal oxygen uptake (muVO2), VO2 at the anaerobic threshold (theta an), the time constant for VO2 kinetics (tau VO2), and work efficiency (eta)) may all be determined reliably from a single test in which the work rate increases continuously at a constant rate, i.e., ramp. That study, however, utilized a single ramp slope of 50 W X min-1, which may not be appropriate for subjects with very low or very high work tolerances. We therefore studied the effect of different ramp slopes on the determination of these parameters. Ramp slopes of 20, 30, 50, and 100 W X min-1 were generated on a cycle ergometer, and each was assigned randomly to 14 healthy subjects. Ventilatory and gas exchange variables were measured breath-by-breath utilizing on-line digital computation. Ramp slopes of 20, 30, and 50 W X min-1 yielded the same values for each aerobic parameter. The 100 W X min-1 ramp yielded muVO2 and eta an values that were the same as those found for the other ramp slopes, but tau VO2 and eta could not be discerned validly from this ramp slope. We conclude that valid assessment of the four parameters of aerobic function is possible with ramp slopes between 20 and 50 W X min-1; no further information on the parameters is to be gained by prolonging the tests with ramps slower than 20 W X min-1.

Adult↗
PubMed1995

Inhibition of ATP-sensitive potassium channels causes reversible cell-cycle arrest of human breast cancer cells in tissue culture.

The purpose of this study was to determine if potassium channel activity is required for the proliferation of MCF-7 human mammary carcinoma cells. We examined the sensitivities of proliferation and progress through the cell cycle to each of nine potassium channel antagonists. Five of the potassium channel antagonists produced a concentration-dependent inhibition of cell proliferation with no evidence of cytotoxicity following a 3-day or 5-day exposure to drug. The IC50 values for these five drugs, quinidine (25 microM), glibenclamide (50 microM), linogliride (770 microM), 4-aminopyridine (1.6 mM), and tetraethylammonium (5.8 mM) were estimated from their respective concentration-response curves. Four other potassium channel blockers were tested at supra-maximal channel blocking concentrations, including charybdotoxin (200 nM), iberiotoxin (100 nM), margatoxin (10 nM), and apamin (500 nM), and they had no effect on MCF-7 cell proliferation, viability, or cell cycle distribution. Of the five drugs that inhibited proliferation, only quinidine, glibenclamide, and linogliride also affected the cell cycle distribution. Cell populations exposed to each of these drugs for 3 days showed a statistically significant accumulation in G0/G1 phase and a significant proportional reduction in S phase and G2/M phase cells. The inhibition of cell proliferation correlated significantly with the extent of cell accumulation in G0/G1 phase and the threshold concentrations for inhibition of growth and G0/G1 arrest were similar. The G0/G1 arrest produced by quinidine and glibenclamide were reversed by removing the drug, and cells released from arrest entered S phase synchronously with a lag period of approximately 24 hours. Based on the differential sensitivity of cell proliferation and cell cycle progression to the nine potassium channel antagonists, we conclude that inhibition of ATP-sensitive potassium channels in these human mammary carcinoma cells, reversibly arrests the cells in the G0/G1 phase of the cell cycle, resulting in an inhibition of cell proliferation.

4-Aminopyridine↗
PubMed1989

Ventilatory control of the 'isocapnic buffering' region in rapidly-incremental exercise.

During incremental exercise PCO2 does not fall for several work rates ('isocapnic buffering') above the anaerobic threshold (theta an). We explored this apparent lack of compensatory hyperventilation in 24 normal subjects who underwent incremental cycling (15 W/min) to exhaustion. Ventilation, pulmonary gas exchange, and end-tidal gas tensions were computed breath-by-breath. In 10 subjects, arterial blood was sampled every 2 min throughout the test. Our findings confirmed the 'isocapnic' supra-theta an region, but it consistently followed a progressive increase of PETCO2 in the sub-theta an region. A similar pattern was evident for PaCO2. The leveling-out of PETCO2 and PaCO2 was a result of breathing frequency increasing at theta an, thereby shortening expiratory time, i.e., progressively truncating the continued increase in the alveolar PCO2 slope. Consequently 'isocapnic buffering' during incremental exercise does not reflect PCO2 which continues to be regulated at a constant sub-theta an value. Rather it reflects a ventilatory response to the metabolic acidosis which levels a systematically-rising phase of PETCO2 and PaCO2, largely through a change in breathing pattern. Respiratory compensation, as reflected by a declining PETCO2 and PaCO2, does not occur typically for a subsequent 2 or more minutes.

Acid-Base Equilibrium↗
PubMed1988

Effect of Army basic training in sickle-cell trait.

In order to determine if sickle-cell trait (SCT) represents an inherent adverse effect on response to training, we objectively evaluated exercise performance in 22 healthy, black men with SCT (hemoglobin AS) and 15 controls (hemoglobin AA) before and after seven weeks of army basic training at an altitude of 1270 m. An incremental exercise test to exhaustion on a cycle ergometer was used. Before basic training, peak exercise measurements did not reveal significant differences between groups other than a slightly lower, albeit significant, value for oxygen uptake (VO2) per kilogram (42 +/- 1 vs 45 +/- 1.4 mL/min per kilogram) for the SCT group. Both groups experienced modest overall cardiovascular improvement reflected in both peak and submaximal exercise responses. No statistically significant difference was observed between the SCT and the control groups at the end of basic training for any of the measured variables at peak exercise, including power (258 +/- 6 vs 266 +/- 9W), VO2 (3.24 +/- .06 vs 3.36 +/- .16 L/min), VO2 per kilogram (46 +/- 0.7 vs 46 +/- 1.2), minute ventilation (138 +/- 4 vs 147 +/- 8 L/min), heart rate (185 +/- 2 vs 184 +/- 3 beats per minute), oxygen pulse (17.6 +/- .3 vs 18.4 +/- 1 mL/min per beat), as well as anaerobic threshold (1.81 +/- .04 vs 1.80 +/- .06 L/min), respectively. No medical problems directly attributed to SCT were reported; it remains uncertain, however, whether a seizure experienced by one of the other SCT basic trainees after a two-mile run was SCT related. The results of this study would, therefore, suggest that for the majority of individuals who possess SCT, the response to the moderate training regimen provided by army basic training is not impaired.

Adult↗
PubMed2006

Modelling of aerobic and anaerobic energy production during exhaustive exercise on a cycle ergometer.

An extension of the original hyperbolic model (Model-2) was proposed by using power output required to elicit maximal oxygen uptake (Pt). This study aimed to test this new model (Model-alpha) using mechanical work produced during cycle ergometry. Model alpha assumed that power exceeding a critical power (Pc) was met partly by the anaerobic metabolism. The parameter alpha was the proportion of the power exceeding Pc provided by anaerobic metabolism, while power exceeding Pt was exclusively met by anaerobic metabolism. Aerobic power was assumed to rise monoexponentially with a time constant tau. The exhaustion was assumed to be reached when the anaerobic work capacity W' was entirely utilised. Twelve subjects performed one progressive ramp test to assess the power at ventilatory threshold (P(VT)) and Pt and five constant-load exercise to exhaustion within 2-30 min, with one to estimate the maximal accumulated oxygen deficit (MAOD). Parameters from Model alpha were fitted with tau equal to 0, 10, 20 and 30 s. Results in goodness-of-fit was better than Model-2 whatever the value assumed for tau (P < 0.05). The value of tau did not affect much the estimates for P (c) and alpha. P (c) estimates were significantly correlated with Pc from Model-2 and with P(VT). W' estimates, which were dependent on the value ascribed to tau, were not statistically different than MAOD. These two variables were, however, not significantly correlated. In conclusion, Model alpha could provide useful information on the critical power and the anaerobic contribution according to exercise intensity, whereas W' estimates should be used with care because of the sensitivity to the assumption on aerobic power kinetics tau.

Algorithms↗
PubMed2005

[DNA content analysis in thyroid neoplasms: diagnostic and prognostic interest].

Thyroid nodules are frequent and sometimes they pose a diagnostic and prognostic problem. DNA ploidy study and cell cycle analysis could be of value in the distinction between benign tumors and malignant tumors. Formalin-fixed and paraffin-embedded tissues from 69 patients with different benign and neoplastic lesions were investigated. Nuclear DNA content in thyroid cells was measured after Feulgen staining using SAMBA 200 image analysis system. A diploid DNA stemline was revealed in 75% of histologically proven benign thyroid tumors (15/20) and aneuploidy was found in 57.2% of malignant tumors (28/49). There is a significant correlation between aneuploidy and extra-thyroid extension (p=0.007) and bilateral and/or mediastinal lymph node metastasis (p=0.02). In the majority of benign tumors (19/20), the proliferation index was lower than 3% (< or =3%) however, this index value was higher than 3% (>3%) in more than 83% of malignant tumors (41/49) (p<0.001). The S phase fraction analysis revealed that the threshold of 14% divide the near whole of benign and malignant tumors (p<0.001). Our findings show that in follicular lesions, proliferation index and S phase fraction study appears interesting and helpful in the distinction between benign and malignant tumors, and aneuploidy seems more interesting in prognosis evaluation of these tumors.

Aneuploidy↗
PubMed2000

The role of technical, biological, and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. VII. Seasonal influences on anticonvulsant drug actions in mouse models of generalized seizures.

Seasonal or circannual rhythms have been reported in various physiologic, biochemical, pharmacological, and toxicological studies in mice and rats despite laboratory conditions with standardized and controlled light cycle, temperature, humidity, and food. This may either be explained by the existence of innate, free-running circannual rhythms or by the existence of seasonally varying environmental factors ('zeitgeber') which are detected by the animals despite controlled laboratory conditions. In the present study, it was evaluated whether circannual rhythms affect the anticonvulsant activity of phenobarbital, carbamazepine, or valproate in two mouse models of generalized seizures, i.e. the threshold for generalized tonic seizures in the maximal electroshock seizure (MES) test and the threshold for different types of generalized seizures induced by the chemical convulsant pentylenetetrazol (PTZ). A study protocol was used with data sampling in separate groups of mice per month (using each group only once) over a period of 13 months beginning and ending in late summer (September), so that data collected in the other seasons could be compared with summer values of 2 subsequent years. With all three anticonvulsants, marked seasonal variation was observed in both seizure models with lowest anticonvulsant efficacy and potency in March and April, i.e. in late winter and early spring. The most marked loss of anticonvulsant activity in this period of the year was observed with valproate. Analysis of drug levels in plasma and brain indicated that the seasonal variation in phenobarbital's and carbamazepine's anticonvulsant effect was predominantly due to alterations in drug metabolism leading to reduced brain levels in March and April, while the seasonal rhythm in valproate's activity appeared to be mainly related to altered pharmacodynamic activity. These findings indicate that the time of the year is an important variable in the experimental evaluation of anticonvulsant drugs. Furthermore, the present data add to the accumulating evidence that endogenous circannual rhythms should be considered during animal experiments under controlled laboratory conditions.

Animals↗
PubMed2003

Estimating the effects of 17alpha-ethinylestradiol on populations of the fathead minnow Pimephales promelas: are conventional toxicological endpoints adequate?

Environmental benchmarks have recently been proposed for several steroids including the synthetic steroid, 17alpha-ethinylestradiol (EE2). These benchmarks are based on extrapolation from studies involving long-term exposure of various fish species to EE2. One of the critical studies was a complete life-cycle experiment performed with the fathead minnow Pimephales promelas over a 289 day exposure period. The lowest observed effect concentration (LOEC) and the no observed effect concentration (NOEC) for gonad histology were 4 and 1 ng L(-1) respectively. This was because no testicular tissue could be found in any fish exposed to 4 ng L(-1). In the present paper, the survival and reproduction data from that study are reanalyzed to determine the effects of EE2 on the intrinsic rate of population growth (r = In (lambda)), a parameter of demographic importance. We estimate critical threshold concentrations with respect to r and compare these with those previously derived from conventional toxicity test summaries. Further, we assess the influence of individual variability on threshold estimates using a combination of bootstrap and regression approaches, together with a suite of perturbation analyses. These yield ErC100 values (the concentration estimated to reduce intrinsic growth rate to zero) of 3.11 ng L(-1) (linear model) and 3.41 ng L(-1) (quadratic model), comparable with a maximum acceptable toxicant concentration (MATC) of 2 ng L(-1) for feminization of exposed fish calculated by Laenge et al. Our results indicate that reduction in population growth rate with increasing concentration occurred more through EE2 acting to reduce fertility than survival rates. The significance of these summary statistics when deriving environmental benchmarks for steroid estrogens is discussed in the context of affording protection to populations following long-term exposure.

Animals↗
PubMedDate not supplied

Effects of amiodarone and its metabolite, desethylamiodarone, on the electrophysiologic properties of isolated cardiac muscle.

The electrophysiologic (EP) effects of chronically administered amiodarone (AM) is known, but the nature of its acute effects are unclear. Whether the delayed onset of AM action is due to its metabolite, desethylamiodarone (DAM), is also uncertain. By standard microelectrode techniques in isolated canine ventricular muscle (VM) and Purkinje fibers (PF) and in rabbit sinoatrial (SA) node and atrium, we therefore studied the comparative effects of AM and DAM, 10(-6) M (0.68 micrograms/ml), 10(-5) M (6.8 micrograms/ml), and 5 X 10(-5) M (34 micrograms/ml), dissolved in ethanol and homologous serum. In VM, PF, and atria stimulated at 1 Hz, AM and DAM had no effect on Vmax, action potential amplitude (APA), or resting membrane potential. At 2-4 Hz, AM exerted a marked use-dependent effect in VM and PF. In atria, 5 X 10(-5) M, AM and DAM increased (p less than 0.01) action potential duration at 90% repolarization (APD90); the effective refractory period (ERP) increased by 10.5% (p less than 0.05 for AM) and 21.6% (p less than 0.01 for DAM). In VM, AM increased APD90 by 9.6% (p less than 0.01) at 10(-6) M, 13.7% (p less than 0.01) at 10(-5) M, and 16.9% (p less than 0.01) at 5 X 10(-5) M. The corresponding values for DAM were 5.6% (NS), and 7.3% (p less than 0.01), respectively. The ERP in VM was increased significantly by AM but not by DAM at all 3 drug concentrations without a change in APD90/ERP ratio. In PF, AM and DAM decreased APD50 and APD90; the effects were greater than those produced by the superfusion medium, but the degree of shortening in ERP induced by AM and DAM was not. AM and DAM (10(-5) and 5 X 10(-5) M) increased spontaneous cycle length of rabbit SA node. AM significantly decreased slope of phase 4 depolarization (10.4% at 10(-6) M, p less than 0.05; 14.5% at 10(-5) M, p less than 0.01; 24.0% at 5 X 10(-5) M, p less than 0.01). At 5 X 10(-5) M, AM significantly decreased APA, maximum diastolic potential and threshold potential with an insignificant effect on APD100.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1996

Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody.

Although histologically benign, one-third of all pituitary tumors will be invasive of surrounding structures. In this study, the relationship between the proliferative activity in pituitary adenomas and their invasiveness was investigated. Invasion was defined as gross, operatively or radiologically apparent infiltration of dura or bone. Using the recently developed MIB-1 monoclonal antibody, which recognizes the Ki-67 cell cycle-specific nuclear antigen, the growth fractions of 37 noninvasive adenomas, 33 invasive adenomas, and 7 primary pituitary carcinomas were determined. All tumors were fully classified by histology, immunohistochemistry, and electron microscopy. The mean Ki-67 -derived growth fractions for noninvasive adenomas, invasive adenomas, and pituitary carcinomas were 1.37 +/- 0.15%, 4.66 +/- 0.57%, and 11.91 +/- 3.41%, respectively (mean +/- standard error of the mean). An analysis of variance and then individual pairwise comparisons confirmed significant differences in the mean Ki-67 labeling index between each of the three tumor groups (P < 0.01). The mean growth fraction of hormonally active pituitary adenomas (3.25 +/- 0.26%) was significantly higher than that for nonfunctioning adenomas (2.06 +/- 0.23%) (P = 0.03). Establishing a threshold labeling index of 3% served to distinguish invasive from noninvasive adenomas with 97% specificity and 73% sensitivity and was associated with positive and negative predictive values of 96 and 80%, respectively. Although invasive pituitary tumors exhibited significantly higher growth fractions than did noninvasive tumors, there were individual exceptions, indicating that in a subpopulation of invasive pituitary tumors, factors other than proliferative activity determine invasive potential.

Adult↗