Prenatal androgens time neuroendocrine puberty in the sheep: effect of testosterone dose

In sheep, prenatal exposure to androgens during a critical period for sexual differentiation of the brain (30-90 days of gestation; 145 days is term) can advance the timing of puberty in females and prevent the preovulatory LH surge. The present study tests the hypothesis that in sheep, the timing of neuroendocrine sexual maturation is related to the amount of prenatal steroid exposure. In addition, we determined if different steroid requirements exist for sexual differentiation of the tonic and surge modes of gonadotropin secretion. Testosterone was administered weekly to three groups of pregnant ewes from days 30-90 of gestation at doses of 200, 80, or 32 mg/week. The resulting androgenized female lambs together with control males and females (n = 5-7/group) were gonadectomized at 3 weeks of age, and gonadal steroids were replaced with a SILASTIC brand estradiol-filled capsule. LH concentrations were measured from biweekly blood samples. Sustained increases in circulating LH were considered to reflect the initiation of neuroendocrine puberty. In male lambs, LH secretion started to increase at 8.3 +/- 0.9 weeks of age (mean +/- SEM). The two highest doses of prenatal androgen advanced the onset of neuroendocrine sexual maturation in females. In the 200 mg androgenized females, the pubertal LH rise (10.2 +/- 2.0 weeks) began about the same time as in males. In the 80 mg treatment group, LH concentrations increased at 16.2 +/- 1.5 weeks, which was later than in males, but well before that in normal females (27.1 +/- 0.7 weeks). For females treated with the lowest dose of androgen (32 mg), the pubertal LH increase (24.6 +/- 1.9 weeks) began about the same time as in normal females. To test the function of the LH surge system, LH was measured every 2 h for 60 h after an acute increase in circulating estradiol was produced by implanting additional estrogen capsules. All control females produced a surge in response to acute estradiol stimulation. LH surges did not occur in males, 200 mg androgenized females, or 80 mg androgenized females. Of six females from the 32 mg treatment group, two produced LH surges in response to the stimulatory feedback action of estradiol. We conclude that the greater the amount of prenatal testosterone, the earlier the initiation of the pubertal LH rise. Moreover, the finding that low doses of testosterone (32 mg/week) are capable of abolishing the LH surge without significantly advancing the timing of puberty supports our hypothesis that different steroid requirements exist for sexual differentiation of tonic and surge modes of LH secretion.     

The absorbed dose to bone marrow in the treatment of polycythaemia by 32P

This paper reports the determination of absorbed dose to bone marrow in the treatment of polycythaemia by 32P, based on the measurement of activities in bone and marrow biopsies taken at various times from 1 to 27 days after injection of the radionuclide. Activities were measured in the cortex, trabeculation and marrow of biopsies taken from the iliac crest, and slso in sternal marrow. The biological half-life of 32P in marrow from the iliac crest was found to be nine days; that derived for sternal marrow was lower, but the difference was not statistically significant; the value for trabecular bone was 27 days. The biological half life for 32P in the body, as measured by whole-body counting, was 39 days. Calculations of the dose-rate to trabecular marrow have been made by a method based on that of Whitwell and Spiers (1971), but modified to allow for the presence of32P in the marrow as well as in trabecular bone. The dose-rates follow a single exponetial decay with a half-life of 6.7 days. The intergrated dose including that during the first day is 24 rad per mCi injected.     

Estimation of radiation absorbed doses to the red marrow in radioimmunotherapy

Myelotoxicity is the dose-limiting factor in radioimmunotherapy. Traditional methods most commonly used to estimate the radiation adsorbed dose to the bone marrow of patients consider contributions from radionuclide in the blood and/or total body. Targeted therapies, such as radioimmunotherapy, add a third potential source for radiation to the bone marrow because the radiolabeled targeting molecules can accumulate specifically on malignant target cells infiltrating the bone marrow. A non-invasive method for estimating the radiation absorbed dose to the red marrow of patients who have received radiolabeled monoclonal antibodies (MoAb) has been developed and explored. The method depends on determining the cumulated activity in three contributing sources: 1) marrow; 2) blood; and 3) total body. The novel aspect of this method for estimating marrow radiation dose is derivation of the radiation dose for the entire red marrow from radiation dose estimates obtained by detection of cumulated activity in three lumbar vertebrae using a gamma camera. Contributions to the marrow radiation dose from marrow, blood, and total body cumulated activity were determined for patients who received an I-131 labeled MoAb, Lym-1, that reacts with malignant B-lymphocytes of chronic lymphocytic leukemia and nonHodgkin's lymphoma. Six patients were selected for illustrative purposes because their vertebrae were readily visualized on lumbar images. The radiation doses to the marrow contributed by nonpenetrating emissions in the marrow blood and penetrating emissions in the total body were similar in these patients with a mean of 0.2 and 0.3 rads per administered mCi from the blood and total body, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of absorbed oxygen on the kinetics of chemical reactions on metal surfaces

The effects of adsorbed impurities on the kinetics of reactions on metal surfaces are discussed, in particular the reactions of water vapor and carbon dioxide with iron surfaces are analyzed. The critical oxygen potentials for the onset of ‘poisoning’ of the reactions appear to correspond with the onset of facetting of iron and the formation of surface phases on the iron. The maximum chemical reaction rate constants for the reactions of water vapor and of carbon dioxide on iron surfaces at a given temperature are shown to correspond closely to the chemical reaction rate constants determined from the reduction of iron oxides in their respective systems. The phenomena observed on the reaction of gases with iron and iron oxide surfaces are reported in other metal systems thus the analysis used for the present reactions appears to be applicable to other systems involving metal/gas reactions.     

The regional Monte Carlo method: a dose calculation method based on accuracy requirement

In this work we propose the regional Monte Carlo (RMC) method of dose calculation. This method combines the Monte Carlo (MC) algorithm and a non-MC algorithm (such as the convolution method) for optimal speed and accuracy in dose calculation for both photon and electron beams and for various irradiation and patient geometries. For specific regions in the geometry where high accuracy is required but difficult to obtain with analytical or empirical calculations, such as critical organs surrounded by complicated inhomogeneities, the MC algorithm is used. For regions with simple geometries, or where a high degree of dose accuracy is not critical, the non-MC algorithm is used to increase speed. There are two aspects of the RMC method. The first one involves determining critical regions and boundaries, and the other involves the actual implementation and mixing of the two computational algorithms. Two examples of different geometries are used to illustrate the different ways to apply the RMC method. The possibility to extend the method to more complicated geometries and inhomogeneities, as well as the ability of the method to incorporate different calculation algorithms, are also discussed.     

An estimate of the nucleation time in the martensitic transformation

A method for the determination of nucleation times for martensitic transformation is described. The method utilizes a shock wave that, upon being reflected at a free surface, generates a tensile wave with a pulse duration that increases as it moves away from the surface. Once the duration of the reflected pulse is large enough for nucleation to occur, transformation can take place. The width of the martensite free layer adjoining the surface is measured and compared with wave predictions. A nucleation time can be obtained. The method requires that the temperature, pulse amplitude, and alloy composition be such that only the reflected tensile wave induce martensite transformation. For the experimental conditions used by Snell, Shyne, and Goldberg¹⁰ the nucleation time is found to be less than 55 nanoseconds. MARC A. MEYERS, formerly Assistant Professor, Department of Metallurgical Engineering, South Dakota School of Mines and Technology     

Conversion of ionization measurements to radiation absorbed dose in non-water density material

The radiation absorbed dose to non-water equivalent materials of interest in radiotherapy is the dose to lung and the dose to bone. The measurement and calculation of dose to the lung has been of great interest and much effort has gone into the development of accurate lung dose calculation methods. The radiation absorbed dose to the bone is usually not calculated and most absorbed dose calculations have been done without correcting for the presence of bone. For the lower megavoltage photon beams this may be appropriate, however, as the energy of the photon beam increases, the region of electronic disequilibrium becomes larger and pair production which depends on the atomic number of the material becomes significant. Therefore the bone will produce greater perturbations of the dose distribution. The dose to lung-equivalent material is uniquely obtained from ionization measurements. However, in bone-equivalent materials two different calculations of absorbed dose are possible: the absorbed dose to soft tissue plastic (polystyrene) within bone-equivalent material and the dose to the bone-equivalent material itself. Both can be calculated from ionization measurements in phantoms. These two calculations result in significantly different doses in a heterogeneous phantom composed of polystyrene and aluminium (a bone substitute). The dose to a thin slab of polystyrene in aluminium is much higher than the dose to the aluminium itself at the same depth in the aluminium. Monte Carlo calculations confirm that the calculation of dose to polystyrene in aluminium can be accurately carried out using existing dosimetry protocols. However, the conversion of ionization measurements to absorbed dose to high atomic number materials cannot be accurately carried out with existing protocols and appropriate conversion factors need to be determined.     

On absorbed dose in narrow 60Co gamma-ray beams and dosimetry of the gamma knife

Using separate analytical functions describing primary dose, P0(dm,r), collimator scatter, Sc(r), and phantom scatter, TAR(d,r), an expression for absorbed dose in narrow 60Co gamma-ray beams is developed and each function is quantified: D(d,r) = P0(dm,r) Sc(r) TAR(d,r). The absorbed dose is calculated in beams as narrow as 0.2 cm in radius. Analytical and experimental results are compared using measured dose data for the Gamma Knife. Close agreement with experimental data is observed.     

The effect of maternal obesity on the accuracy of fetal weight estimation

OBJECTIVE: To determine if maternal obesity affects the accuracy of either clinical or sonographic fetal weight estimations. METHODS: In a year-long study, 998 singleton pregnancies of 26-43 weeks' gestation underwent both clinical (Leopold) and sonographic (Shepard and Hadlock) fetal weight estimation within 5 days of delivery (mean 1.1, 95% confidence interval 1.0-1.3). Patients were stratified into four different groups based on increasing maternal body mass index (BMI): underweight (less than 19.8), normal weight (19.8-26.0), overweight (26.1-29.0), and obese (more than 29.0). The various estimations of fetal weight were compared with actual birth weight, and the mean absolute percent error was calculated for each specific method and analyzed among the four BMI groups. RESULTS: For each method of weight estimation, there was no difference (specifically, no increase) in the magnitude of the absolute percent error with increasing maternal obesity. Regardless of maternal size, almost half of the weight predictions were within 5% of the actual birth weight. CONCLUSION: Increasing maternal obesity does not alter or decrease the accuracy of either clinical or sonographic fetal weight estimations. Therefore, fetal weight predictions provide equally accurate and valid guidelines for determining management decisions in women, regardless of body size.     

The Fort Bragg evaluation: A snapshot in time.

The recently completed Fort Bragg Child and Adolescent Mental Health Demonstration Project (L. Bickman, see record 83-31861; L. Bickman et al, 1995) has provided an opportunity to develop a fully comprehensive continuum of mental health and substance abuse services. However, the study's findings have raised questions concerning the usefulness of the continuum of care and the effectiveness of changing the structure of service delivery on clinical practice and outcomes. The author discusses the planning, methodology, and implementation of the project, and offers some additional insights into potential pitfalls in the evaluation of complex programs and the risks for drawing sweeping conclusions from a study done at a point in time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pressure measurement evaluation and accuracy validation: the Gabarith test

OBJECTIVE: The dynamic distortion introduced by manometric systems has been known for many years, with several methods developed to describe and quantify the degree of distortion. We developed the Gabarith as a technique to describe more accurately, and yet more simply, the dynamic accuracy of the chain of monitoring. SETTING: A pressure monitoring system transforms some input signal, i.e. the actual pressure waveform present in the artery, into some other shape of waveform, i.e. the waveform displayed on the patient monitor. This transformation is characterized by the transfer function of the total system. A complete technique to define the transfer function is to measure the response directly at many different frequencies and combine them to produce the dynamic response plot. METHOD: We described the dynamic response of a monitoring chain and we simplified the communication of this dynamic response to users by developing the Gabarith, as a tolerance envelope based on the frequency content of typical pressure waveforms. If a given monitoring chain's dynamic response (including a catheter, a pressure kit and a monitor) can be shown to fall within that tolerance envelope, the chain will provide adequate dynamic accuracy. CONCLUSION: "Gabarith tested" means that a pressure kit, in combination with a catheter and a monitor, has had its frequency response function measured and that the function falls within a tolerance band for dynamic accuracy. Passing a Gabarith means that a given level of accuracy will be reached when using the sets which have passed the corresponding test.     

The disposition of nifurtimox in the rat isolated perfused liver: effect of dose size

The disposition of nifurtimox was studied in the rat isolated perfused liver using a recirculating system. The drug was administered as a bolus (5.0, 15.0 or 30.0 micrograms mL-1), and its disappearance was monitored by analysing perfusate samples. In all experiments perfusate disappearance was monoexponential, and no significant difference was found between the three doses for the elimination constant (0.016, 0.011 and 0.012 min-1, respectively), half-life (46.6, 65.8 and 66.8 min, respectively), extraction rate (0.128, 0.091 and 0.099, respectively) and distribution volume (41.1, 47.3 and 30.7 mL g-1, respectively). At 30 micrograms mL-1 the hepatic clearance was lower than the other concentrations of nifurtimox (0.66, 0.51 and 0.34 mL min-1 g-1, respectively). Relatively little parent drug was recovered from the liver at the end of the perfusions. In summary, nifurtimox is cleared slowly from the rat isolated perfused liver, is poorly extracted by hepatocyte cells and is completely metabolized from 2 to 4 h after perfusion.     

A software tool for the quantitative evaluation of 3D dose calculation algorithms

Current methods for evaluating modern radiation therapy treatment planning (RTP) systems include the manual superposition of calculated and measured isodose curves and the comparison of a limited number of calculated and measured point doses. Both techniques have significant limitations in providing quantitative evaluations of the large number of dose data generated by modern RTP systems. More sophisticated comparison techniques have been presented in the literature, including dose-difference and distance-to-agreement (DTA) analyses. A software tool has been developed that uses superimposed isodose plots, dose-difference, and DTA distributions to quantify errors in computed dose distributions. Dose-difference and DTA analyses are overly sensitive in regions of high- and low-dose gradient, respectively. The logical union of locations that fail both dose-difference and DTA acceptance criteria, termed the composite evaluation, is calculated and displayed. The composite evaluation provides a method for the physicist to efficiently identify regions that fail both the dose-difference and DTA acceptance criteria. The tool provides a computer platform for the quantitative comparison of calculated and measured dose distributions.     

Ideomotor apraxia in early Alzheimer's disease: time and accuracy measures

Twenty-six Alzheimer's disease (AD) and 42 healthy control (NC) subjects were evaluated with neuropsychological and apraxia batteries. ADs produced a greater range of error types, but did not differ from NCs in their most frequent error types. Hand sequencing ability contributed significantly to AD praxis with no predictors for NCs. Although groups did not differ in gesture time, the AD group had significantly longer response latencies for periods prior to gesture execution and the effect was prominent for transitive tasks and nondominant hand use. Results illustrate the sensitivity of timing measures in identifying abnormal praxis in early stages of AD.     

Patch testing with budesonide in serial dilutions: the significance of dose, occlusion time and reading time

Dipeptide transporters in small intestine have a very wide substrate specificity, so that the transporter sometimes serves as a carrier for peptide-like compounds. We have synthesized dipeptide analogues conjugated at an epsilon-amino group of Lys in Val-Lys or Lys-Sar with fluorescent compounds such as fluorescein isothiocyanate and coumarin-3-carboxylic acid. Uptakes of these peptide analogues were examined by measuring intracellular accumulations into monolayers of the human intestinal epithelial cell line Caco-2 expressing the dipeptide transporter PEPT1. Kinetic analysis and effects of addition either of uncoupler (protonophore) or by Gly-Sar, one of the good substrates of PEPT1, revealed that fluorescent dipeptides were taken up by passive diffusion. In contrast, these analogues remarkably inhibited the Gly-Sar uptake by Caco-2 cells. Among the fluorescent analogues synthesized in this paper, Val-Lys(Flu) was the most potent competitive inhibitor against the Gly-Sar uptake with an inhibition constant of 5 microM. This value is the smallest among those ever reported: Val-Lys(Flu) has the highest affinity for PEPT1 among chemicals ever reported. The importance of the hydrophobic part of the substrate was pointed out.     

The effect of intestinal transit time on bacterial translocation

Increase in intraluminal bacterial count, disruption of the mucosal integrity, changes in intestinal immunity and transit time are the factors involved in bacterial translocation. The relationship between intestinal transit time, intra luminal bacterial count and translocation rate were investigated in 40 Wistar-albino rats. The study was conducted in 4 groups with 10 animals in each. Group I (controls): saline + laboratory chow, Group II: saline + oral total parenteral nutrition (TPN) solution, Group III: morphine sulfate (MS) + oral TPN solution, Group IV: neostigmine bromide (NB) + oral TPN solution. Intestinal transit time was measured by using Indium111-labeled diethylene triamine pentaacetic acid (DTPA). It was prolonged in the MS-treated group and shortened in the NB-treated group (p < 0.01). The frequency of bacterial translocation was 60% in the oral TPN solution group, 100% in the MS-treated group, 20% in the NB-treated group and 10% in controls. Bacterial counts in duodenum, jejunum, ileum and caecum were significantly increased (p < 0.001) in the MS-treated group and decreased (p < 0.05) in the NB-treated group in comparison with the control group. In conclusion, the prolongation of intestinal transit time increased the intraluminal bacterial count and augmented bacterial translocation. The decrease in intestinal transit time had a converse effect.