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PubMed1999

Detection of lysergic acid diethylamide (LSD) in urine by gas chromatography-ion trap tandem mass spectrometry.

A confirmatory method for the detection and quantitation of lysergic acid diethylamide (LSD) is presented. The method employs gas chromatography-tandem mass spectrometry (GC-MS-MS) using an internal ionization ion trap detector for sensitive MS-MS-in-time measurements of LSD extracted from urine. Following a single-step solid-phase extraction of 5 mL of urine, underivatized LSD can be measured with limits of quantitation and detection of 80 and 20 pg/mL, respectively. Temperature-programmed on-column injections of urine extracts were linear over the concentration range 20-2000 pg/mL (r2 = 0.999). Intraday and interday coefficients of variation were < 6% and < 13%, respectively. This procedure has been applied to quality-control specimens and LSD-positive samples in this laboratory. Comparisons with alternate GC-MS methods and extraction procedures are discussed.

Gas Chromatography-Mass Spectrometry↗
PubMed2004

Alterations in gene expression induced in day-9 mouse embryos exposed to hyperthermia (HS) or 4-hydroperoxycyclophosphamide (4CP): analysis using cDNA microarrays.

Teratogen-induced alterations in gene expression play an important role in the genesis of malformations in animals. The recent development of DNA microarrays now offers the opportunity to monitor global changes in gene expression and therefore the potential to obtain significant new information concerning both normal and abnormal development. RNA was isolated from day-9 mouse embryos at 1 and 5 h after exposure to hyperthermia (HS) or 4-hydroperoxycyclophosphamide (4CP) and compared to RNA isolated from concurrent controls using mouse cDNA microarrays. Cy5/Cy3 intensity data were extracted using Spot-on Image software and then normalized using the statistical software program R/maanova. Differentially expressed genes were identified using a linear mixed-effects model and p values derived from t-test statistics. Approximately 9000 genes show statistically significant alterations in expression in day-9 mouse embryos exposed to HS or 4CP. HS and 4CP also induce alterations in the expression of distinct sets of genes, e.g., DNA replication/repair, cell cycle, signal transduction, and transcription-related genes. As expected, a variety of heat shock genes are upregulated by HS but not 4CP. Among genes whose expression is altered by both HS and 4CP, cluster analysis identified three p53 target genes (Cyclin G1, Gtse1, and Mdm2), and follow up studies confirmed that p53 is activated in embryos exposed to these two teratogens. In addition, cluster analyses also revealed that HS but not 4CP induces the downregulation of genes encoding key enzymes in the cholesterol biosynthesis pathway. Thus, our microarray data have identified one potentially important pathway (p53) common to both HS- and 4CP-induced teratogenesis and another pathway (cholesterol biosynthesis) potentially important, but specific to HS-induced teratogenesis.

Animals↗
PubMed2003

Palatal surface area measurement: comparisons among different cleft types.

The purpose of this study was to use three-dimensional imaging methods to measure the palatal surface of unrepaired cleft patients. The surface area of the palate was defined and measured on three-dimensional computed tomography images of dental plaster models in four different groups of cleft patients at 3 months of age. There were 30 unilateral complete cleft lips and palates (UCLP), 27 bilateral complete cleft lips and palates (BCLP), 23 isolated cleft palates of incomplete form (CP), and 19 unilateral cleft lips without cleft palates (UCL). These patients were nonsyndromic, unoperated, and without other major deformities. The dental casts were scanned, and the computed tomography data were transferred to an imaging laboratory for processing and reconstruction of three-dimensional images. Surface area of the palate was delineated, which was defined as within the alveolar crest and the line connecting both tuberosities. In UCLP and BCLP, the edge of cleft formed the medial boundary of the area for each palatal shelf, and the palatal surface area was the combination of both palatal shelves and the premaxillary area in BCLP group. The surface area was measured. Repeated definition and measurement tasks were performed for calculation of errors. The imaging data management and measurement were performed using the Analyze program (Biomedical Imaging Resource, Mayo Foundation, MN). In addition, linear distances were measured between the canine points on the alveolar crest (line C) and the tuberosity points (line T). The measurements were compared among the different groups. Analysis of variance and multiple comparisons were used for statistical analyses. The results showed that the mean error between repeated area definitions and measurements in this study was 1.86%. The bilateral complete cleft lip and palate (BCLP) and unilateral complete cleft lip and palate (UCLP) groups had significantly smaller palatal surface area than the unilateral cleft lip without cleft palate (UCL) and isolated cleft palate of incomplete form (CP) groups. There was no significant difference between the BCLP and UCLP groups. Line C and line T distances were significantly longer in BCLP and UCLP groups than in UCL and CP groups. The findings suggest that compared with UCL and CP patients, there is an intrinsic tissue deficiency in the palate/maxilla of BCLP and UCLP patients.

Cleft Lip↗
PubMed2005

Optimal unravellings for feedback control in linear quantum systems.

For quantum systems with linear dynamics in phase space much of classical feedback control theory applies. However, there are some questions that are sensible only for the quantum case: Given a fixed interaction between the system and the environment what is the optimal measurement on the environment for a particular control problem? We show that for a broad class of optimal (state-based) control problems (the stationary linear-quadratic-Gaussian class), this question is a semidefinite program. Moreover, the answer also applies to Markovian (current-based) feedback.

Journal Article↗
PubMed1980

The role of the codon and the initiation factor IF-2 in the selection of N-blocked aminoacyl-tRNA for initiation.

Poly(uridylic acid) [poly(U)] and poly(xanthidylic acid) [poly(X)] strongly stimulate the IF-2-dependent binding of fMET-tRNA to 30-S ribosomal subunits from Escherichia coli [Van der Laken et al. (1979) FEBS Lett. 100, 230-234]. The N-formylmethionine moiety is incorporated into poly(phenylalanine) upon subsequent addition of other components required for protein synthesis when poly(U) is used as template. This paper shows that N-acetylated Phe-tRNAPhe (AcPhe-tRNA), but not Phe-tRNAPhe or tRNAPhe, competes with fMET-tRNA for binding to poly(U)-programmed 30-S ribosomal subunits. The two species of N-blocked aminoacyl-tRNA are bound to poly(U)-programmed and poly(X)-programmed 30-S subunits in a ratio that is linearly dependent on the ratio of the two species added. With poly(U) as template there is no apparent preference for either fMET-tRNA or AcPhe-tRNA, whereas with poly(X) there is a 2-3-fold preference for fMET-tRNA. The initiation factor IF-2, which is strictly required for the binding of N-blocked aminoacyl-tRNAs, has a higher affinity for fMET-tRNA than for AcPhe-tRNA. It is concluded that (a) interaction of the 30-S ribosomal subunit with poly(U) or poly(X) leads to IF-2-dependent binding of N-blocked aminoacyl-tRNA; (b) the initiation factor IF-2-discriminates in favour of fMET-TRNA; (c) the presence of the cognate codon discriminates in favour of the corresponding N-blocked aminoacyl-tRNA.

Codon↗
PubMed1985

Detection and characterization of four binding sites for opioids in the mouse brain.

The binding sites labelled by 3H-dihydromorphine, 3H-ethylketocyclazocine and 3H-D-Ala2-L-Leu5-enkephalin in mouse brain membranes were characterized in cross-competition studies. The data was evaluated by simultaneous non-linear least-squares regression analysis with the "Ligand" program (Munson & Rodbard 1980), that had to be upgraded to handle more than three binding sites. By statistical analysis four different binding sites were identified. Three of the sites probably correspond to the pharmacologically well characterized mu, kappa and delta-opioid receptors, respectively, and their binding capacities relate as 1:1.5:2.5. Classification of the fourth site is more problematic. Using 3H-ethylketocyclazocine it had higher capacity than the others and bound ethylketocyclazocine with a relatively high affinity (Kd = 10 nM), dihydromorphine with a very low affinity (Kd greater than 10(-5)M) and showed no binding of D-Ala2-L-Leu5-enkephalin. In displacement studies, N-allylnorcyclazocine (SKF 10,047), though unselective, bound with highest affinity to the mu and the fourth site. Since naloxone did not bind to this fourth site, it can not be termed an opioid site in a strict sense, but it might have some relevance in view of non-naloxone-reversible effects reported for some opioids.

Animals↗
PubMed2006

Clinical implementation of target tracking by breathing synchronized delivery.

Target-tracking techniques can be categorized based on the mechanism of the feedback loop. In real time tracking, breathing-delivery phase correlation is provided to the treatment delivery hardware. Clinical implementation of target tracking in real time requires major hardware modifications. In breathing synchronized delivery (BSD), the patient is guided to breathe in accordance with target motion derived from four-dimensional computed tomography (4D-CT). Violations of mechanical limitations of hardware are to be avoided at the treatment planning stage. Hardware modifications are not required. In this article, using sliding window IMRT delivery as an example, we have described step-by-step the implementation of target tracking by the BSD technique: (1) A breathing guide is developed from patient's normal breathing pattern. The patient tries to reproduce this guiding cycle by following the display in the goggles; (2) 4D-CT scans are acquired at all the phases of the breathing cycle; (3) The average tumor trajectory is obtained by deformable image registration of 4D-CT datasets and is smoothed by Fourier filtering; (4) Conventional IMRT planning is performed using the images at reference phase (full exhalation phase) and a leaf sequence based on optimized fluence map is generated; (5) Assuming the patient breathes with a reproducible breathing pattern and the machine maintains a constant dose rate, the treatment process is correlated with the breathing phase; (6) The instantaneous average tumor displacement is overlaid on the dMLC position at corresponding phase; and (7) DMLC leaf speed and acceleration are evaluated to ensure treatment delivery. A custom-built mobile phantom driven by a computer-controlled stepper motor was used in the dosimetry verification. A stepper motor was programmed such that the phantom moved according to the linear component of tumor motion used in BSD treatment planning. A conventional plan was delivered on the phantom with and without motion. The BSD plan was also delivered on the phantom that moved with the prescheduled pattern and synchronized with the delivery of each beam. Film dosimetry showed underdose and overdose in the superior and inferior regions of the target, respectively, if the tumor motion is not compensated during the delivery. BSD delivery resulted in a dose distribution very similar to the planned treatments.

Algorithms↗
PubMed2000

Simulation of circular array ultrasound transducers for intravascular applications.

The beam shape of a circular array transducer that is commonly used in intravascular ultrasound catheters was investigated in linear mode of operation. For this use, a simulation program which can simulate the radio frequency (rf)-response of a number of scatterers has been developed. The program is based on the impulse response method, which is implemented in the frequency domain. Due to the unusual geometry of the transducer, the far field gets peculiarly shaped for large apertures. Instead of having a far field with its maximum intensity in a single lobe on the acoustical axis, the far field splits up into a dual-lobe far field with maximum intensity in two lobes off the acoustical axis. A formula is derived that predicts the occurrence of these beam shapes.

Coronary Vessels↗
PubMed1976

New assay of protective activity of Rocky Mountain spotted fever vaccines.

Areas under the fever curves of guinea pigs inoculated with Rocky Mountain spotted fever vaccine over a restricted dose range and infected with a standardized dose of Rickettsia rickettsii varied linearly with log10 dose of vaccine. A calculator was programmed to plot fever curves and calculate the vaccine dose that reduced the fever of infected animals by 50%.

Animals↗
PubMed1987

Conditional factors of maturing out: personal resources and preaddiction sociopathy.

The study continues exploration of the conditional nature of the process of maturing out of narcotics addiction over time. It tests hypotheses about the relationship of selected personal resource/sociodemographic variables (including ethnicity and employability) and preaddiction sociopathy characteristics to maturing out. Hypotheses were tested using log-linear models on data from the California Civil Addict Program. Results suggest that while the process of maturing out over time is not substantially different depending upon level of preaddiction sociopathy or ethnicity, the process may be influenced by levels of other personal resource characteristics.

Adult↗
PubMed1998

Morning versus evening amlodipine treatment: effect on circadian blood pressure profile in essential hypertensive patients.

OBJECTIVE: To determine the antihypertensive efficacy and the potential impact on circadian blood pressure pattern of morning versus evening administration of amlodipine to essential hypertensive patients. METHODS: Twelve mild-to-moderate essential hypertensives were investigated in this open, randomized cross-over study. Blood pressure and heart rate were measured by use of ambulatory blood pressure monitoring after a wash-out period of 1 week and after treatment schedules with 5 mg amlodipine once a day either at 0800 h or at 2000 h for 3 weeks. Effects were evaluated by linear and rhythm analysis using the ABPM-FIT program. RESULTS: Both morning and evening administrations of amlodipine significantly (P < 0.01) reduced the elevated systolic and diastolic blood pressures during daytime. However, due to baseline values being lower during night-time, a significant (P < 0.05) reduction was observed only in systolic, not in diastolic, blood pressure. Maximal blood pressure values were significantly (P </= 0.01) decreased by both treatment regimens, whereas nightly minimum values remained unchanged. The early morning rise in blood pressure was decreaseed after morning and slightly more pronounced aftger evening dosing of amlodipine. Though both amlodipine treatments more effectively reduced daytime blood pressure levels, the circadian profile was not greatly affected. Amlodipine treatment had no effect on heart rate. CONCLUSION: The results demonstrate that, independently from the dosing time, the long-acting calcium antagonist amlodipine sufficiently reduced blood pressure in essential hypertensive patients without increasing the nightly drop. The drug-induced decrase in the early morning rise in blood pressure may be advantageous in reducing the early morning cardiovascular risk.

Journal Article↗
PubMed1976

Dose distribution of therapeutic electron beams and automation of treatment planning.

Until the present time, there has been no mathematical evaluation of the therapeutic electron beams in tissue material. Electron treatments are becoming universally applied from betatrons and linear accelerators. There is, therefore, a need for dosimetric programming of hospital computers for electron treatment planning such as those used in photon beam dosimetry. In this study, we have developed a theoretical model for dose calculation in a clinical therapeutic electron beam (Osman, 1972 and 1973). On the basis of this proposed theory, one can predict dose profiles at any source to skin distance "SSD"' and at any depth in tissue "X". Our theoretical model is based on considering the clinical broad electron beam used in radiation therapy as being made up of an infinite number of identical and initially parallel pencil beam components, each of minute width, to which the existing theories (Lewis, 1950; Attix et al., 1968) on electron multiple scattering, in the concerned medium apply. Dose profiles in tissue, as obtained from this model, could provide useful information as input data for routine programs of treatment planning with high energy electron beams, using mini-computers. Further, it is also possible to account for any body inhomogeneity such as subcutaneous fat, lung, air volumes, body cavities, fluids and bone from the basic parameters of these media.

Automation↗
PubMedDate not supplied

[Cyclosporin pharmacokinetic modeling in renal transplant patients].

AIM: To characterize the pharmacokinetic behavior of oral cyclosporin (CsA) in renal transplant patient, based on through blood concentration (C0) value, and to develop and to evaluate a Bayesian method for the individualized adjustment of CsA daily dose (DD). METHODS: Sixty-seven renal allograft recipients (42 men and 25 women) who had been treated with CsA (Sandimmun Neoral) associated with mycophenolate mofetil (2g daily) and prednisone (0,5-1 mg/kg daily) were randomly divided into two groups. Group A (N=48) was used to characterize CsA pharmacokinetic behavior and Group B (N=19) to evaluate Bayesian predictive performance for the model developed. We evaluated different structural models using non linear mixed effects modeling implemented in the NONMEN computer program in order to quantify the relationship between DD and C0. Accuracy and precision were evaluated by the mean standardized prediction error and its standard deviation. RESULTS: The Michaelis-Menten model was found to be optimum for quantifying the relationship between DD and C0. This model includes time-dependent parameters such as the Michaelis-Menten constant (Km) and daily maximum dose (Dmax) as well as first order autoregressive terms DD and C0 included in the structural model in an additive way. In the final model, the Dmax parameter is affected by plasmatic urea values and shows a half-life stabilization time of 90.90 days (95% CI: 52.60 to 250 days). Plasmatic urea values of 50 mg/dL are related to an initial Dmax value of 3 mg/kg daily (95% CI: 1.81 to 4.19 mg/kg daily) which decreases exponentially throughout the post-transplant period until it reaches a constant value of 2.16 mg/kg daily (95% CI: 1.41 to 2.91 mg/kg daily) In the same way, the Km parameter presents a central tendency value of 93.60 ng/mL (95% CI: 28.60 to 158.60 ng/mL) and the half-life necessary for its stabilization is 12.70 days (95% CI: 9.80 to 17.90 days). The residual variability of the model is 8.2%. The mean value of standardized prediction errors for populations and its standard deviation, as well as its confidence intervals of 95%, confirm the appropriate accuracy and precision of both a priori and a posteriori predictions with this model. Also, it reached between 70 and 100% a posteriori sequential predictions with prediction errors below 10%. CONCLUSION: The characterization of the pharmacokinetic behavior of CsA requires us to consider parameters such as Dmax and Km as non lineal functions of time, while the first order autoregressive terms DD and C0 must also be incorporated into the model.

Adult↗
PubMed1991

A time-series analysis of longitudinal weight changes in two adult women.

This study was conducted to examine individual longitudinal serial trends in body weight of two moderately obese adult women. Self-measured daily weights (over 5000 data points for subject 1 and over 3500 for subject 2) were averaged for each month and analyzed using a time-series analysis approach. The best statistical model for both women indicated a significant upward trend (gain 30 and 22 lb, respectively) interrupted by linear decreases (P less than 0.05) during weight loss programs over the 16- and 10-year observation periods, respectively. The women participated in six and eight weight control programs, respectively, and consistently lost weight, averaging 9.17 +/- 1.85 lb and 8.00 +/- 3.57 lb. Both subjects regained weight after dieting, in a period approximately 2.25 times as long as the diet. Numerous weight fluctuations occurred and one subject lost and then regained 10 percent of her body weight during two 5-year periods. Results are examined in terms of a possible weight increase protection benefit, as well as the deleterious medical potential that may occur with numerous weight loss attempts. Suggestions for future research are provided regarding weight cycling, seasonal variations, set point theory, aging effects, and the use of self-directed weight loss initiatives in conjunction with formal weight reduction programs. This study may serve as a prototype for exploring weight fluctuation using time-series analyses and for further investigating the etiology and clinical management of obesity.

Body Mass Index↗
PubMed1987

Simulated grading decisions of allied health educators: a survey of Texas faculty.

Using simulated student data, this study investigated the grading decisions and future performance expectations of faculty members from allied health programs in Texas. These randomly selected faculty members evaluated linear and nonlinear grade profiles and formed expectations of students' future performances based on these grade profiles. Results indicated that student grade-performance patterns were differentially related to assigned grades and future expectations. Factors related to overall grade assignment included mean performance level, slope of academic performance (ascending, descending), and time of performance change (early, late). Two potential grading biases were suggested (age, sex of faculty), particularly for ascending performance patterns. Other faculty characteristics were unrelated to grading decisions and expectations.

Achievement↗
PubMed1980

[Structural and adaptational insufficiency of the myocardium and its quantitative analysis].

A concept of the pathogenesis of cardiac insufficiency explaining the decompensation mechanism from the point of view of premature realization of genetically determined program of age adaptation of cardiomyocytes materially based on linear increase of the volumetrical density of mitochondria is suggested. The etiological factors accelerating the time course of this process produce the effect of premature "ageing" of muscle cells and decrease of the contractile capacity of the myocardium and its adaptation abilities inadequate for the age requirements. A quantitative measure of the adaptation reserve is the difference between the maximum (40%) and actual, that is, altered, volumetric density of mitochondria the value of which may be established by myocardial biopsy. The degree of decompensation is determined by the difference between the actual and age (definite for each age) value of this parameter, the possibility of correction of this process being inversely proportional to this value.

Adaptation, Physiological↗
PubMed1995

PC program for determining the dose necessary to produce a given amount of change.

Given a simple linear regression equation of the form D = alpha + beta Z, it is well-known how to predict, and construct confidence intervals for, the value of D corresponding to a given Z. In this paper we describe, illustrate and make available a menu-driven PC program which can be used to solve the inverse problem, namely, to estimate and construct confidence intervals for the value of Z corresponding to a given value of D. We describe the procedure in the context of a dose-response relationship, where it is desired to estimate the dose (Z) to effect a given amount of change (D), but the method is more general than this. In particular, it may be usefully applied in calibration problems where one may wish to estimate the true value of a measurement given the value as read from a measuring device.

Antimony↗