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Dosimetric pre-treatment verification of IMRT using an EPID; clinical experience.

BACKGROUND AND PURPOSE: In our clinic a QA program for IMRT verification, fully based on dosimetric measurements with electronic portal imaging devices (EPID), has been running for over 3 years. The program includes a pre-treatment dosimetric check of all IMRT fields. During a complete treatment simulation at the linac, a portal dose image (PDI) is acquired with the EPID for each patient field and compared with a predicted PDI. In this paper, the results of this pre-treatment procedure are analysed, and intercepted errors are reported. An automated image analysis procedure is proposed to limit the number of fields that need human intervention in PDI comparison. MATERIALS AND METHODS: Most of our analyses are performed using the gamma index with 3% local dose difference and 3mm distance to agreement as reference values. Scalar parameters are derived from the gamma values to summarize the agreement between measured and predicted 2D PDIs. Areas with all pixels having gamma values larger than one are evaluated, making decisions based on clinically relevant criteria more straightforward. RESULTS: In 270 patients, the pre-treatment checks revealed four clinically relevant errors. Calculation of statistics for a group of 75 patients showed that the patient-averaged mean gamma value inside the field was 0.43 +/- 0.13 (1SD) and only 6.1 +/- 6.8% of pixels had a gamma value larger than one. With the proposed automated image analysis scheme, visual inspection of images can be avoided in 2/3 of the cases. CONCLUSION: EPIDs may be used for high accuracy and high resolution routine verification of IMRT fields to intercept clinically relevant dosimetric errors prior to the start of treatment. For the majority of fields, PDI comparison can fully rely on an automated procedure, avoiding excessive workload.

Electronic Data Processing↗

Suppression of aromatase activity in vitro by PCBs 28 and 105 and Aroclor 1221.

The effects of polychlorinated biphenyls (PCBs) on human cytochrome P450 aromatase activity in vitro were investigated using a commercially available microsomal fraction obtained from baculovirus infected insects that had been transfected with the human CYP19 gene and cytochrome P450 reductase. The assay measured the conversion of tritiated testosterone to estradiol in Tris buffer at pH 7.4. When aroclors, commercial preparations of PCBs, were added to aromatase assays at a 10 microM concentration, Aroclor 1221 caused a reduction in the aromatase activity, whereas other aroclors (1016, 1232, 1242, 1248, 1254, 1260, 5432, 5442 and 5460) were without effect. Further investigation of the effect of Aroclor 1221 on aromatase activity showed that the inhibition was dose dependent. When a reconstituted mixture (RM) of PCBs that represented the congeneric content of human milk was investigated, no inhibition of aromatase activity at the maximum treatment of 15.0 microM was observed. None of the congeners present in the reconstituted mixture, except PCB 28 and 105, affected P450 arom activity. PCB 28 showed a statistically significant inhibition of aromatase activity (P<0.05) at 1.5 and 15 microM and a significant inhibition of aromatase activity by PCB 105 was also observed, but only at 15 microM. In three separate kinetic analyses the Km(app) for aromatase was 64, 89 and 69 nM (mean 74 nM). In addition, PCB 28 resulted in an increase in the Km(app) without a significant effect on Vmax(app), suggesting competitive inhibition by this congener. This conclusion was supported by slope (Km(app)/Vmax(app) versus [inhibitor]) and intercept (1/Vmax(app) versus [inhibitor]) replots. The slope replots gave Ki(app) values for PCB 28 of 0.9, 1.3 and 2.0 microM (mean 1.4 microM), whereas intercept replots were almost horizontal. Thus, PCB 28 is a competitive inhibitor of aromatase with a Ki(app) value approximately 20-fold the Km(app) value. Based on these studies, we conclude that most PCBs are not inhibitors of aromatase activity in vitro. However, as being inhibitors of aromatase activity, Aroclor 1221, PCB 28 and PCB 105 would remain a priority for further study as possible endocrine disrupters.

Animals↗

Parametric analysis of carotid plaque using a clinical ultrasound imaging system.

We evaluated quantitative ultrasonic methods for assessment of carotid plaque content. In vitro measurements of fixed, carotid plaque specimens obtained by surgical endarterectomy were performed using a clinical Philips HDI 5000 imaging system connected to a radiofrequency (RF) signal-acquisition system. We acquired RF signals and grey-scale images from carotid specimens (n = 17) and a tissue-mimicking reference phantom. Imaged plaque sections were then classified according to histology. Parametric images were constructed from the integrated backscatter (IBS), and the midband, slope and intercept values of a straight-line fit to the apparent backscatter transfer function. Analysis was performed on 82 regions-of-interest (ROIs). The IBS values for collagen, lipid and hemorrhage plaques were 5.8 +/- 5.4, 3.9 +/- 3.7, 2.8 +/- 2.2 dB, respectively. Midband and IBS parameter images exhibited good agreement in morphology with histology, whereas the slope and intercept parameter images were noisy. Mean IBS, midband, and grey-scale values of complex plaques were found to be statistically different (p < 0.05) from lipid, hemorrhage and fibrolipid plaques. The bias and limits of agreement (1.3 +/- 4.9 dB) between the grey-scale and IBS methods, however, indicated that the two methods were not interchangeable. Results indicate necessary improvements, such as reduction of large measurement variances and identification of robust parameters, that will permit multiparametric characterization of carotid plaque under in vivo conditions.

Carotid Arteries↗

Point-of-purchase messages framed in terms of cost, convenience, taste, and energy improve healthful snack selection in a college foodservice setting.

OBJECTIVE: To examine the effects of a point-of-purchase (POP) intervention emphasizing various properties of healthful food items on college students' snack purchases. DESIGN: In Study 1, vegetable baskets (containing cut pieces of vegetables), fruit baskets (containing cut pieces of fruit), pretzels, and yogurt were promoted in separate POP interventions. Food sales were monitored over 2-week baseline, 4-week intervention, and 2-week follow-up periods. In Study 2, yogurt was promoted across a 2-week baseline, 12-week intervention, and 2-week follow-up periods and an intercept survey was conducted. SUBJECTS/SETTING: Approximately 2,280 university students were potentially exposed to the intervention, and 72 students responded to the intercept survey. INTERVENTION: POP messages were placed on an 11 x 17-in poster located at the cafeteria entrance, and two 4 x 2.5-in signs placed next to the targeted food item. Messages emphasized the Budget-friendly, Energizing, Sensory/taste, Time efficient/convenient (BEST) stimulus properties of food. MAIN OUTCOME MEASURES: Daily sales of the targeted food items. STATISTICAL ANALYSES PERFORMED: Analyses of variance with Tukey post hoc tests were used to compare food sales during the baseline, intervention, and follow-up periods. RESULTS: In Study 1, yogurt and pretzel sales increased during the intervention and post-intervention periods (P<.05). Interventions had no effect on fruit basket and vegetable basket sales (P>.05), but whole fruit sales increased during the fruit basket intervention and follow-up (P<.05). In Study 2, yogurt sales were significantly greater during the intervention and follow-up periods than at baseline (P<.01). APPLICATIONS/CONCLUSIONS: Using the BEST properties in POP interventions may be beneficial in promoting the consumption of healthful foods among university students, particularly when the targeted foods are priced comparably to less healthful foods.

Canada↗

Vectorcardiographic diagnosis of diaphragmatic myocardial infarction.

Vectorcardiograms of 31 patients with arteriographic evidence of complete occlusion of the right coronary artery were analyzed in order to evaluate and attempt to improve the vectorcardiographic criteria for the diagnosis of an old diaphragmatic myocardial infarction. The electrocardiogram showed no evidence of a diaphragmatic infarction in 48 percent of these patients. This was advantageous, since the intent of the study was to develop vectorcardiographic criteria that exceeded the capability of the electrocardiogram. The criteria that appeared optimal were: (1) an instantaneous 0.02 second QRS vector equal or superior to 315 degrees (-45 degrees) in the sagittal plane, or (2) ratio of voltages of 0 to left x-intercept to maximal QRS vector greater than 0.22 in the frontal plane. These criteria identified a diaphragmatic infarction in 77 percent of patients (24 of 31) with complete occlusion of the right coronary artery. There were no false positive findings in 40 normal subjects. A group of criteria previously defined by others, based upon rotation, contour of initial forces, duration of superior forces relative to the contour, magnitude of 0 to left x-intercept, and maximal QRS vecotr, was equally sensitive. Other previously defined criteria were less sensitive. The criteria developed in this study, when tested in 22 patients with prominent Q waves indicative of an old diaphragmatic infarction, properly diagnosed the infarction in all 22 patients. All previous criteria also successfully detected infarction in these patients. However, the new criteria identified a greater number of patients without electrocardiographic evidence of diaphragmatic infarction than were identified with previously defined vectorcardiographic criteria unless the latter were complex.

Action Potentials↗

Limits of reproducibility of blood flow measurements by Doppler echocardiography.

This study evaluates the variability of a quantitative Doppler echocardiographic method for blood flow calculation at the mitral and tricuspid orifice. Four subjects underwent 2-dimensional Doppler echocardiography during normal respiration and nonrespiration. Doppler recordings were integrated to determine mean temporal velocity (MTV) for each cardiac cycle separately. MTV during inspiration and expiration were compared, as were MTVs of 20 consecutive cycles during nonrespiration. Diameters of mitral and tricuspid orifice and interception angles were measured in 10 consecutive cycles at 4 predetermined moments. All results were averaged to a mean subject situation. MTVs were significantly (p less than 0.001) higher during expiration than during inspiration (12.4 and 11.0 cm-2) for the mitral orifice and lower (9.2 and 11.0 cm-2) for the tricuspid orifice. MTV at both orifices showed a significantly smaller variability (7.7% and 9.0%) during nonrespiration than during respiration (14.5% and 13.2%). Diameters of mitral orifice and tricuspid orifice were significantly (p less than 0.001) larger during diastole than during systole whereas standard error of the mean for both was 5.0%. Interception angles measured at mitral orifice are all close to 0 degrees and show minimal variability, while at the tricuspid orifice the angle varied from 15 degrees in diastole to 25.5 degrees in systole, constituting a significant difference in cosine (0.96 to 0.90).

Adult↗

Lay beliefs about high blood pressure in a low- to middle-income urban African-American community: an opportunity for improving hypertension control.

PURPOSE: Lay beliefs about illness are a potential barrier to improving the control of hypertension. We investigated the extent to which lay beliefs about hypertension diverge from current medical understanding. METHODS: We conducted street intercept interviews and focus group discussions in six predominantly African-American census tracts in the southern sector of Dallas County, Texas. Sixty subjects, aged 18 to 67 years, were stopped along popular thoroughfares and administered a brief survey. Additionally, 107 participants were interviewed in 12 homogeneous focus groups, balanced by sex and age (18 to 74 years). Participants were asked about the meaning, causes, consequences, and treatment of high blood pressure. RESULTS: The street intercept data indicated that 35% (n = 21) of respondents related high blood pressure to eating pork or other foods that makes the blood travel too fast to the head, and only 15% (n = 9) related hypertension to an elevated pressure in blood vessels. The focus group data indicated that hypertension was causally linked to eating pork in 8 of the 12 groups; was perceived as a symptomatic illness in all 12 groups; and was considered treatable with vitamins, garlic, and other herbs in 11 groups, with prescription medications in 10 groups and with lifestyle modifications such as weight loss in 8 groups. Hypertension was mentioned as a leading cause of death among African Americans in none of the 4 focus groups of 18-year-old to 29-year-old participants, in 2 of the 4 focus groups of 30-year-old to 49-year-old participants, and in 3 of the 4 focus groups of 50-year-old to 74-year-old participants. CONCLUSIONS: In a low- to middle-income urban African-American community, the predominant beliefs about hypertension diverged sharply from current medical understanding. Lack of appreciation of these lay beliefs by providers may contribute to noncompliance and poor rates of hypertension control.

Adult↗

Role of the endothelium in adrenergic responses of mesenteric artery rings of pregnant rats.

Responses to adrenergic agents were measured on rings of mesenteric, artery of nonpregnant and pregnant rats at 21 days' gestation. In tissues from pregnant rats, norepinephrine, and phenylephrine were less sensitive than in rings from nonpregnant animals; maximum responses were not affected. The effect of isoproterenol was not modified in tissues from pregnant rats. The presence of endothelium in tissue rings was evaluated as fractional relaxation to acetylcholine. Sensitivity to phenylephrine and norepinephrine was inversely related to the effect of acetylcholine. This relationship was similar in slope in both groups but different in intercept. The sensitivity to isoproterenol was directly related to the presence of endothelium (curves similar in both slope and intercept). This demonstrates that the responses of mesenteric artery rings depends on the presence of endothelium. Furthermore, vascular endothelium is not involved in the blunted responses to adrenergic vasoconstrictor during pregnancy.

Animals↗

CA 125 kinetics: a cost-effective clinical tool to evaluate clinical trial outcomes in the 1990s.

OBJECTIVE: Our purpose was to determine the importance of the rate of decline of CA 125 relative to conventional prognosticators of ovarian cancer survival to develop a cost effective management algorithm that supports clinical trial research. STUDY DESIGN: By use of a retrospective chart review the slope of the CA 125 exponential regression curve was calculated for 126 women undergoing combination chemotherapy for epithelial ovarian cancer. Univariate and multivariate survival analyses evaluated conventional parameters including age, grade, stage, histologic features, time to initial chemotherapy, dose and treatment intensity, number of cycles to normal CA 125 levels, the intercept from the regression equation, and the slope of the exponential curve. RESULTS: The ideal CA 125 regression rate was calculated at 7.6 days (95% confidence interval 5.9 to 10.7). Univariate analysis determined slope of the CA 125 exponential regression curve (p = 0.0003), number of cycles to normal CA 125 levels (p = 0.0001), residual disease (p = 0.0006), and platinum treatment intensity (p = 0.0001) as the most important predictors of survival. Cox proportional-hazard regression analysis identified slope of the CA 125 exponential regression curve and number of cycles to normal CA 125 levels as the most significant factors for actuarial survival, replacing such conventional parameters as patient age, stage, grade, chemotherapy intensity, and residual disease. None of the factors investigated predicted treatment outcome for patients without residual disease. Multiple linear regression analysis of the slope of the CA 125 exponential regression curve identified intercept of the regression equation, stage, age, and time to initial chemotherapy as important determinants of the slope. CONCLUSION: The slope of the CA 125 exponential regression curve is the single most important prognosticator of actuarial survival for the patient with a CA 125-positive ovarian carcinoma. Treatment algorithms based on this slope may be helpful in developing novel cost-effective clinical trials.

Adult↗

Complete unloading alone may not adequately protect the left ventricle.

BACKGROUND: The benefit of left ventricular (LV) unloading for preserving LV function is commonly accepted, but its efficacy remains incompletely defined. METHODS: We studied the influence of complete LV unloading on LV systolic and diastolic mechanics using an in situ isovolumic preparation with two different coronary perfusion pressures (CPPs) in 12 dogs during prolonged normothermic cardiopulmonary bypass. RESULTS: Multivariate analysis of covariance with time as a covariate revealed that a high CPP (143 +/- 36 mm Hg; n = 6) was associated with better preservation of systolic LV function over time as assessed by LV end-systolic elastance (p < 0.001) and the end-systolic pressure-volume relation physiologic intercept (p < 0.001) compared with a moderate CPP (107 +/- 18 mm Hg; p < 0.005 versus a high CPP by t-test; n = 6). Dobutamine (2 micrograms.kg-1.min-1) improved LV end-systolic elastance (p < 0.005) and LV physiologic intercept (p < 0.01) only in the high-CPP group. Conversely, impaired LV diastolic function (as measured by LV stiffness) was observed (p < 0.001) with a high CPP, but did not change with a moderate CPP. CONCLUSIONS: These observations in canine hearts suggest that complete LV unloading may not preserve LV systolic function adequately over time when CPP is maintained in the accepted clinical range. A higher CPP is required to prevent deterioration over prolonged cardiopulmonary bypass times, but diastolic dysfunction still occurs.

Animals↗

Inhibition of the bovine-heart mitochondrial F1-ATPase by cationic dyes and amphipathic peptides.

The bovine heart mitochondrial F1-ATPase is inhibited by a number of amphiphilic cations. The order of effectiveness of non-peptidyl inhibitors examined as assessed by the concentration estimated to produce 50% inhibition (I0.5) of the enzyme at pH 8.0 is: dequalinium (8 microM), rhodamine 6G (10 microM), malachite green (14 microM), rosaniline (15 microM) greater than acridine orange (180 microM) greater than rhodamine 123 (270 microM) greater than rhodamine B (475 microM), coriphosphine (480 microM) greater than safranin O (1140 microM) greater than pyronin Y (1650 microM) greater than Nile blue A (greater than 2000 microM). The ATPase activity was also inhibited by the following cationic, amphiphilic peptides: the bee venom peptide, melittin; a synthetic peptide corresponding to the presence of yeast cytochrome oxidase subunit IV (WT), and amphiphilic, synthetic peptides which have been shown (Roise, D., Franziska, T., Horvath, S.J., Tomich, J.M., Richards, J.H., Allison, D.S. and Schatz, G. (1988) EMBO J. 7, 649-653) to function in mitochondrial import when attached to dihydrofolate reductase (delta 11.12, Syn-A2, and Syn-C). The order of effectiveness of the peptide inhibitors as assessed by I0.5 values is: Syn-A2 (40 nM), Syn-C (54 nM) greater than melittin (5 microM) greater than WT (16 microM) greater than delta 11,12 (29 microM). Rhodamines B and 123, dequalinium, melittin, and Syn-A2 showed noncompetitive inhibition, whereas each of the other inhibitors examined (rhodamine 6G, rosaniline, malachite green, coriphosphine, acridine orange, and-Syn-C) showed mixed inhibition. Replots of slopes and intercepts from Lineweaver-Burk plots obtained for dequalinium were hyperbolic indicating partial inhibition. With the exception of Syn-C, for which the slope replot was hyperbolic and the intercept replot was parabolic, steady-state kinetic analyses indicated that inhibition by the other inhibitors was complete. The inhibition constants obtained by steady-state kinetic analyses were in agreement with the I0.5 values estimated for each inhibitor examined. Rhodamine 6G, rosaniline, dequalinium, melittin, Syn-A2, and Syn-C were observed to protect F1 against inactivation by the aziridinium of quinacrine mustard in accord with their experimentally determined I0.5 values.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Segmental cable evaluation of somatic transients in hippocampal neurons (CA1, CA3, and dentate).

This study describes a detailed cable model of neuronal structure, which can predict the effects of discrete transient inputs. Neurons in in vitro hippocampal slices (CA1 and CA3 pyramidal cells and dentate granule neurons; n = 4 each) were physiologically characterized and stained with horseradish peroxidase (HRP). The HRP morphology was approximated with numerous small segments. The cable model included both these segments and spatially dispersed dendritic spines. The transient response function at the soma of the segmental model was numerically derived, and charging responses to simulated current inputs were computed. These simulations were compared with the physiological charging responses from the somatic penetrations, using an analysis of the charging time constants (tau i) and intercepts. The time constant ratio (tau 0/tau 1) did not significantly differ between the observed and simulated responses. A second index of comparison was the equivalent cylinder electrotonic length (L), which was derived using only the tau i values and their intercepts. The L values also did not differ significantly between the observed and simulated transients and averaged 0.91 length constant. Thus, using criteria based only on analysis of charging responses, the segmental cable model recreated accurately the observed transients at the soma. The equivalent cylinder model (with a lumped soma) could also adequately simulate the observed somatic transients, using the same criteria. However, the hippocampal neurons (particularly the pyramidal cells) did not appear to satisfy the equivalent cylinder assumption anatomically. Thus, the analysis of somatic charging transients alone may not be sufficient to discriminate between the two models of hippocampal neurons. Anatomical evidence indicates that, particularly for discrete dendritic inputs, the detailed segmental model may be more appropriate than the equivalent cylinder model.

Animals↗

Validity of unbound digoxin measurements by immunoassays in presence of antidote (Digibind).

Measurement of unbound digoxin in presence of Fab fragments may be useful in management of overdoses. The analysis can be performed on serum directly or on ultrafiltrate of serum. The architecture of the immunoassay may influence the validity of results obtained using these two approaches. We tested this hypothesis by preparing serum mixtures containing various concentrations of digoxin and Digibind and analyzed them by the immunoassays before and after ultrafiltration. Four samples collected from Digibind-treated patients were also analyzed before and after ultrafiltration. The slopes and the y-intercepts of the measured versus the expected values for serum and its ultrafiltrate overlapped for the MEIA digoxin assay. For other three immunoassays tested (ACS:180, Stratus, and On-Line), either the slope or the intercept for measured versus the expected results for serum were significantly different (P < 0.05) than those for ultrafiltrate. Following addition of digoxin and Digibind, differences in results for serum analyzed directly or after ultrafiltration were < 0.50 ng/ml. Comparable samples from digoxin-overdosed patients treated with Digibind had differences of > 1.0 ng/ml. Previous claims reporting direct analysis of digoxin in presence of antidote but not having used patient samples for validation should be revisited. To date, analysis of serum ultrafiltrate by an immunoassay proven not to have matrix bias remains the most accurate approach in measuring unbound digoxin in presence of antidote.

Adult↗

Reference values and methods comparison of a new testosterone assay on the AxSYM system.

OBJECTIVES: We have contributed to the Design Validation Protocol of the new Abbott AxSYM Testosterone assay with a study on reference values and methods comparison. DESIGN AND METHODS: For reference values a population of 45 women and 30 men was tested. In methods comparison, 132 samples for the AxSYM vs. ACS-180, and 30 for the AxSYM vs. Elecsys were used. Pearson and intraclass concordance coefficients and Passing-Bablock test were performed for overall group, men and women. RESULTS: Reference values were 0.9-3.1 (females) and 1.0-30.2 nmol/L (males). Globally, a good agreement between methods in both the AxSYM vs. ACS-180 (slope: 0.88, y-intercept: 0.67, r = 0.961) and the AxSYM vs. Elecsys (slope: 1.08, y-intercept: 0.31, r = 0.935) studies was found. Slightly worse results were observed for women. CONCLUSIONS: The reference range of testosterone by the AxSYM system matches with those published for other methods. An acceptable agreement between the AxSYM Testosterone assay and both a classical (ACS-180) and a more recent (Elecsys) methodology was observed.

Adolescent↗

An enzymatic assay for erythrocyte creatine as an index of the erythrocyte life time.

OBJECTIVES: To establish and estimate an enzymatic measurement of creatine in erythrocytes as an index of the erythrocyte life time. DESIGN AND METHOD: The measurement of creatine in erythrocytes was performed using an enzymatic assay kit that was developed for serum and urine creatine. An erythrocyte sample was subjected to creatine measurement after hemolysis and deproteinization. Performance of the method for creatine measurement in erythrocytes was estimated. Effects of age and gender on the creatine content of erythrocytes were also estimated in 305 normal subjects. RESULTS: The method showed within-run CVs varying from 0.7 to 1.0% (n = 20), and between-day CVs from 1.3 to 1.7% (15 days). Good linearity was observed at least up to 1000 mumol/L as creatine value in hemolyzed sample. The analytical recovery was calculated to be 98.1 +/- 1.3% on average. No considerable interference by various substances, including guanidino compounds and amino acids, with the assay was observed. Excellent correlation was observed between the present method and high performance liquid chromatography. With the unit of mumol/g Hb: slope, 1.034 +/- 0.003 (mean +/- SD); intercept, -0.059 +/- 0.012 (mean +/- SD); correlation coefficient, 0.9996; and Sy.x, 0.069. With the unit of mumol/L RBC: slope, 1.033 +/- 0.003 (mean +/- SD); intercept, -18.23 +/- 3.55 (mean +/- SD); correlation coefficient 0.9996; and Sy.x, 20.40. A significant increase in erythrocyte creatine was observed in females aged 11- to 50 years old as compared with males in the corresponding age bracket, however, a gender difference was not observed in other age bracket. This finding suggests the possibility of a slight decrease in the erythrocyte life time due to menstruation in females. CONCLUSION: This study showed that the present method is favorable for quantifying erythrocyte creatine, and has analytical characteristics suitable for routine work in clinical laboratories.

Adolescent↗

Determination of mean particle volume, a Monte Carlo simulation.

Either length measurements or area measurements may be made on a sample of profiles for the purpose of estimating the mean volume of a population of convex particles. Diameters of spheres, caliper diameters of ellipsoids and intercept lengths are available length measurements. Profile areas can be evaluated by planimetry or point counting. Either all the available profiles in random sections or point sampled profiles can be utilized. We have applied a Monte Carlo simulation to compare several of the stereologic methods for the estimation of the mean volumes of spheres and ellipsoids. Populations of spherical, prolate ellipsoidal and oblate ellipsoidal particles were subjected to random sectioning and measurement. Diameter, point sampled intercept length, area and point sampled area were measured in the case of the spherical particles. With the ellipsoids, the same measurement excepting diameters were performed. The measurements were converted to volumes by the appropriate equations, and the means, the standard deviations of the means and the 95% confidence intervals were determined for increasing sample sizes. All the methods provide estimates that converge on their theoretical mean volumes. The area measurements and particularly the point sampled area measurement show some advantage over the length measurements, but differences among the methods are small, not entirely consistent over the different cases and unlikely to be significant in most real applications.

Algorithms↗

Antifertility effects of the steroid 5 alpha-stigmastane-3 beta, 5, 6 beta-triol 3-monobenzoate on mice.

The steroid 5 alpha-stigmastane-3 beta, 5, 6 beta-triol 3-monobenzoate at a dose of 40 mg/kg of body weight has 100% interceptive activity when administered orally in a single dose during 6-7 days of gestation but it has no action on pregnancy if treated on 10th, 13th or 16th day of pregnancy. The interceptive activity of the steroid is lost by simultaneous injection of prolactin, progesterone or LH.

Abortifacient Agents↗

Force-length relationship in dogs as a measure of protective effect of imidapril on regional myocardial ischemia and reperfusion injury.

Our laboratory previously reported that the end-systolic force-length relationship of the left ventricle provides a better method of evaluating myocardial contractile properties than the left ventricular end-systolic pressure-volume relationship, because it avoids deficiencies of the latter parameter such as dependence of its slope (E(max)) on the volume intercept (V(0)). The slope (E(c)) of the left ventricular end-systolic force-length relationship represents the contractility of functioning myocardium, while its length intercept (L(0)) reflects the length of non-functioning myocardium. However, the effect of regional myocardial ischemia on these parameters, as evaluated by the force-length relationship, remains unknown. To clarify the effects of regional ischemia and angiotensin-converting enzyme inhibition on the myocardium during ischemia-reperfusion, the changes in E(c) and L(0) were determined in anesthetized open-chest dogs. (1) Control group (n=26): Before and after 15 min of complete coronary artery occlusion, as well as after 15 min of reperfusion, left ventricular pressure and volume were simultaneously recorded during inferior vena cava occlusion. The left ventricular force-length relationship was obtained from the pressure and volume of three cylindrical segments of the ventricle, and E(c) and L(0) were calculated. (2) Imidapril group (n=14): Imidaprilat (1 microg/kg/min) was continuously infused from 30 min before ischemia to the end of the experiment, and the same procedures were followed as in the control group. Fourteen out of the 26 dogs (54%) in the control group died of reperfusion-induced ventricular arrhythmias, while only two of the 14 dogs (14%) in the imidapril group did so (P<0.05). In the control group, E(c) was increased during ischemia and remained at the same level after reperfusion. However, E(c) was not altered in the imidapril group. Although L(0) was increased during ischemia and decreased after reperfusion in both groups, the percent increase of L(0) in the imidapril group was significantly smaller than in the control group (8% vs. 32%, P<0.05). With the improvement of these indices, the bradykinin concentration of coronary venous blood increased in the imidapril group (P<0.01). These findings suggest that regional myocardial ischemia increased the average contractility of overall functioning myocardium despite the increased non-functioning myocardium. Moreover, imidapril has a cardioprotective effect against ischemia-reperfusion injury by decreasing infarct size, and through the antiarrhythmic effect and the reversal of increased overall contractility.

Adrenergic beta-Antagonists↗