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PubMed1995

Comparative plasma and tissue pharmacokinetics and drug residue profiles of different chemotherapeutants in fowls and rabbits.

Blood and tissue pharmacokinetics and drug residue profiles of six chemotherapeutants were studied. Ceftriaxone (CEF), intravenously at 50 mg/kg, sulfamonomethoxine (SMM) and sulfaquinoxaline (SQ), orally at 200 mg/kg, and olaquindox (OLA), orally at 50 mg/kg, were administered to young broilers. Penicillin (PEN), intramuscularly at 200,000 U/kg, and albendazole (ALB), orally at 20 mg/kg, were given to rabbits. For each drug, 13-18 groups (n = 5-10 individuals/group) of the dosed animals were killed at different post-dosing times. Drug and/or metabolite concentrations in plasma, liver, kidney, heart, lung, and muscle tissues were analysed by HPLC procedures. Multi-exponential kinetic models were fitted to the observed tissue concentration-time data by applying a non-linear least-squares regression computer program. Tissue half-life, peak tissue concentration, and time of peak tissue concentration were determined. Half-life of CEF, SMM, SQ, OLA, PEN, ALB, and two metabolites of ALB (sulfoxide and sulfone) in various tissues ranged 0.6-1.4, 4.7-9.0, 4.5-18.9, 1.8-3.1, 0.9-3.0, 3.4-9.6, 5.0-16.1 and 7.4-12.2 h. The times required for CEF, SMM, SQ, OLA, PEN, and ALB residue concentrations to decline to 0.1 microgram/g in various tissues ranged from 5.0-11.6, 70.0-110.5, 114.0-179.8, 21.3-30.3, 4.1-24.8 and 47.8-84.4 h. Drug kinetic characteristics in tissues differed significantly from those in plasma, and also varied from tissue to tissue. It is necessary, therefore, to evaluate tissue kinetics when designing dosage regimens in tissue infection chemotherapy with these drugs. Knowledge of tissue kinetics is also important in predicting and controlling drug residues in edible tissues of food-producing animals.

Administration, Oral↗
PubMed1997

A comparison of the standard approach and the NONMEM approach in the estimation of bioavailability in man.

There has recently been concern about confidence intervals calculated using the standard error of parameter estimates from NONMEM, a computer program that uses a non-linear mixed-effects model to calculate relative bioavailability (F), because of possible downward bias of these estimates. In this study an alternate approach, the log-likelihood procedure, was used to calculate the confidence intervals for F from NONMEM. These were then compared with those calculated using the standard error of the parameter estimates, the traditional NONMEM approach, and the standard model-independent method, to determine whether bias exists. By use of data from a single dose, open cross-over study of ibuprofen using 14 healthy male volunteers, NONMEM was shown to give results consistent with those obtained using the standard model-independent method of analysis and could be a useful tool in the determination of F where conditions for using the standard method of analysis are not optimum. The width of the confidence interval for F using the log-likelihood procedure was narrower and non-symmetrical when compared with that obtained using the traditional NONMEM approach. The width of the confidence interval obtained using the traditional NONMEM method was similar to that from the standard approach, however the parameter estimate for F was higher than that obtained from the standard method. This could have been because of an outlier in the data set to which the standard approach is more sensitive. No downward bias was found in the confidence intervals from NONMEM. The bioavailability data set was of relatively low variability and more research with highly variable data is necessary before it can be concluded that the confidence intervals calculated from NONMEM can be used for hypothesis testing.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

An ecological study on the association of public dental health activities and sociodemographic characteristics with caries prevalence in Japanese 3-year-old children.

The aim of this ecological study was to determine the association of the frequency of dental health activities conducted as public health service and sociodemographic characteristics with caries prevalence in Japanese 3-year-old children using data for each municipality as one unit. Data on caries prevalence in 3-year-old children in 2000 were obtained from 3,251 municipalities (almost all municipalities in Japan). Caries prevalence for each municipality was recalculated using the empirical Bayes estimation model to make adjustments for variations in municipalities with small numbers of children. Explanatory factors included annual frequency of dental health activities such as dental health education and topical fluoride application programs and various sociodemographic characteristics. Multiple linear regression analysis was applied to examine the associations between caries prevalence and annual frequency of dental health activities with adjustment of other sociodemographic variables. Variations in caries prevalence in municipalities with small populations became smaller after being adjusted by the empirical Bayes estimation model. Multiple linear regression analysis showed significant associations of caries prevalence with sociodemographic characteristics such as the proportion of residents with university degrees, total fertility rate, and the proportion of workers in the manufacturing industry (p < 0.001). Annual frequency of topical fluoride application showed a significant but relatively weak association with caries prevalence (p < 0.001), explaining only 0.8% of the total variation in caries prevalence, whereas no correlation was found between caries prevalence and annual frequency of dental health education. It was concluded that the effect of the fluoride application service on caries prevalence in 3-year-old children, although statistically significant, was of far lower clinical significance than sociodemographic characteristics.

Cariostatic Agents↗
PubMed1986

Kinetics of methaemoglobin production. (1). Kinetics of methaemoglobinaemia induced by the cyanide antidotes, p-aminopropiophenone, p-hydroxyaminopropiophenone or p-dimethylaminophenol after intravenous administration.

Methaemoglobin profiles have been studied by using ISIS, a simulation package, and NONLIN, a non-linear least-squares analysis regression program. A simple kinetic model which satisfactorily describes methaemoglobin profiles after p-aminopropiophenone (PAPP) administration and 4-dimethylaminophenol (DMAP) administration has been developed. The two compounds differed mainly in their effective rates of elimination. The model less satisfactorily described methaemoglobin profiles after p-hydroxyaminopropiophenone (PHAPP) administration.

Aminophenols↗
PubMed1986

Kinetics of methaemoglobin production. (2). Kinetics of the cyanide antidote p-aminopropiophenone during oral administration.

The kinetics of methaemoglobin production by orally administered p-aminopropiophenone (PAPP) was studied by using a kinetic model previously developed to describe methaemoglobinaemia consequent on intravenous injection of PAPP. Both ISIS, a simulation package, and NONLIN, a non-linear least-squares regression analysis program, were used to analyse the data. Some modification of the model was necessary to describe oral profiles and 40-50% of the administered PAPP appeared to be being metabolized at first pass to a non-active metabolite.

Administration, Oral↗
PubMed2004

Cardiovascular responses to a high-volume continuous circuit resistance training protocol.

The purpose of this investigation was to determine the level of cardiovascular stress elicited by continuous and prolonged circuit resistance training (CRT). Each of the 11 men who volunteered as a subject were tested to determine oxygen consumption and heart rate responses to a submaximal and maximal treadmill protocol and a CRT session consisting of 10 exercises and 10 repetitions at 40% of 1 repetition maximum (1RM) for each station with 4.6 circuits performed. The physiological stress of the CRT in this study was evident by the sustained heart rate of more than 70% of maximum for 16.6 minutes, with the last 12 minutes at more than 80%. Despite the large anaerobic component in CRT, Vo(2) was sustained at 50% or more of maximum for the final 12 minutes. Treadmill running, involving large muscle groups, increased Vo(2) more rapidly than CRT, where alternating larger and smaller muscle groups were used. In addition, at the same Vo(2) heart rate differed significantly between the 2 modes of activity. Heart rate in CRT was higher (at 165) than the heart rate of 150 found during treadmill running at the same 50% Vo(2). Such workouts may be used in a training cycle in classical linear periodization or in a nonlinear program day targeting local muscular endurance under intense cardiorespiratory conditions, which may help individuals develop enhanced toleration of physiological environments where high cardiovascular demands and higher lactate concentrations are present.

Adult↗
PubMed1989

Population pharmacokinetic analysis of bisoprolol.

The technique of population pharmacokinetic analysis was employed to study the variability in the dose concentration relationship of bisoprolol during its clinical development. The influence of demographic factors on the variability of clearance was investigated in 3 different populations: group I, patients (including an elderly group) with essential hypertension receiving multiple oral doses of bisoprolol 10 or 20mg for 3 months; group II, patients with different degrees of renal impairment and healthy controls; and group III, patients with different types of hepatic impairment and healthy controls. Patients and controls in groups II and III received only a single oral dose of bisoprolol 10mg. The 3 data sets were analysed separately, using a non-linear mixed effects model (the NONMEM program). A 2-compartment pharmacokinetic model with first-order absorption described the data adequately. The typical values of volume of central compartment, volume of distribution at steady-state and the absorption rate constant for the 3 populations were: for group I, 68L, 235L, and 0.7h-1; for group II, 28L, 179L, and 0.3h-1; and for group III, 55L, 256L, and 0.4h-1, respectively. Plasma clearance was related to age in group I, to serum creatinine in group II and to aspartate transaminase activity in group III. The 68% confidence limits for clearance and elimination half-life were 8.2 to 21.5 L/h and 7.6 to 19.7h, respectively, for 50-year-old patients in group I. The analysis predicted that progressive increases in serum creatinine or aspartate transaminase activity will result in only a 50% reduction of clearance.

Adrenergic beta-Antagonists↗
PubMed2001

Factors of the innovation, organization, environment, and individual that predict the influence five systematic reviews had on public health decisions.

OBJECTIVE: To determine the extent to which systematic reviews of public health interventions influenced public health decisions and which factors were associated with influencing these decisions. METHODS: This cross-sectional follow-up survey evaluated the use of five systematic reviews in public health decision making. Independent variables included characteristics of the innovation, organization, environment, and individual. Primary data were collected using a telephone survey and a self-administered organizational demographics questionnaire. Public health decision makers in all 41 public health units in Ontario were invited to participate in the study. Multiple linear regression analyses on the five program decisions were conducted. RESULTS: The systematic reviews were perceived as having the greatest amount of influence on decisions related to program justification and program planning, and the least influence on program evaluation decisions. The greater the perception that one's organization valued the use of research evidence for decision making and that ongoing training in the critical appraisal of research literature was provided, the greater the perception of the influence the systematic review had on public health decisions. CONCLUSIONS: Organizational characteristics are important predictors of the use of systematic reviews in public health decision making. Future dissemination strategies need to promote the value of using systematic reviews for program decision making as well as promote ongoing training in critical appraisal among intended users in Ontario.

Cross-Sectional Studies↗
PubMed2003

Background correction in forensic photography. I. Photography of blood under conditions of non-uniform illumination or variable substrate color--theoretical aspects and proof of concept.

The combination of photographs taken at two or three wavelengths at and bracketing an absorbance peak indicative of a particular compound can lead to an image with enhanced visualization of the compound. This procedure works best for compounds with absorbance bands that are narrow compared with "average" chromophores. If necessary, the photographs can be taken with different exposure times to ensure that sufficient light from the substrate is detected at all three wavelengths. The combination of images is readily performed if the images are obtained with a digital camera and are then processed using an image processing program. Best results are obtained if linear images at the peak maximum, at a slightly shorter wavelength, and at a slightly longer wavelength are used. However, acceptable results can also be obtained under many conditions if non-linear photographs are used or if only two wavelengths (one of which is at the peak maximum) are combined. These latter conditions are more achievable by many "mid-range" digital cameras. Wavelength selection can either be by controlling the illumination (e.g., by using an alternate light source) or by use of narrow bandpass filters. The technique is illustrated using blood as the target analyte, using bands of light centered at 395, 415, and 435 nm. The extension of the method to detection of blood by fluorescence quenching is also described.

Biophysical Phenomena↗
PubMed2002

[Determination of guanfu base A hydrochloride in plasma by LC-MS method and its pharmacokinetics in dogs].

AIM: To establish an analytical method for determination of guanfu base A (GFA) concentration in plasma and to study its pharmacokinetic profile in dogs. METHODS: Six dogs were given a 7.56 mg.kg-1 dose intravenously. Blood samples were collected at various time-points after drug administration. Analytical method based on liquid chromatography-mass spectrometry (LC-MS) was established to determine the plasma concentration of GFA. Pharmacokinetic evaluation was carried out using the 3P87 program. RESULTS: The calibration curves were linear over the concentration range from 0.42 microgram.mL-1 to 21.2 micrograms.mL-1 (gamma = 0.9994). The intra-day and inter-day precisions were generally good (< 15%) at low, medium and high concentrations. The overall recovery of the analytes was more than 80%. Six dogs were given an i.v. dose of 7.56 mg.kg-1 of GFA hydrochloride, an open three compartment model best described the concentration-time profiles for GFA. The half-lives for the rapid and slow distribution phase and terminal elimination phase (T1/2 pi, T1/2 alpha and T1/2 beta) were 0.07 h, 1.5 h, and 13.5 h, respectively. The total area under the plasma concentration-time curve (AUC), the volume of the central compartment (Vc), and plasma clearance (CLs) were 61.43 micrograms.h.mL-1, 0.37 L.kg-1 and 0.14 L.kg-1.h-1, respectively. CONCLUSION: The analytical method was shown to be sensitive, specific, rapid and reproducible, and was suitable for pharmacokinetic studies of GFA.

Aconitum↗
PubMed1995

Allosteric regulation of proton translocation by a vacuolar adenosinetriphosphatase.

The kinetics of nucleoside-triphosphate-dependent proton translocation by a vacuolar-type adenosine-triphosphatase have been studied, using the enzyme from bovine chromaffin-granule membranes, purified and reconstituted into proteoliposomes. The reaction was followed by recording the quenching of the fluorescence of the permeant weak base 9-amino-6-chloro-2-methoxyacridine; fluorescence data were collected and stored in digital form, and the initial reaction rates estimated by linear regression. In the absence of nucleoside diphosphate, the dependence of initial rates of proton translocation on substrate concentration were fitted well by the Michaelis-Menten equation, as were the kinetics of ATP hydrolysis. ADP and other nucleoside diphosphates were potent inhibitors of the ATPase, effecting a reduction in the maximum velocity of the reaction, and producing sigmoid substrate-saturation curves which could be fitted by the empirical Hill equation, the Hill coefficient approaching 2 at high inhibitor concentrations. Data sets containing initial-rate estimates were collected over a wide range of independently varied concentrations of substrate and inhibitor and were modeled, using rate equations derived from several different models based on the concerted-transition model of allosteric inhibition proposed by Monod, Wyman and Changeux. These equations were fitted to the data by weighted non-linear regression, using an iterative computer program to obtain the best estimates of kinetic parameters. One model consistently fitted all of the data sets better than all the others, and this model was based on the following assumptions: that the ATPase exists in two conformational states, R and T; that only the R state is catalytically active; that each state contains three kinetically equivalent catalytic sites, and one regulatory site; that nucleoside triphosphates bind only to the catalytic sites, and that nucleoside diphosphates bind both to the catalytic sites and to the regulatory site. The optimized values of the kinetic parameters indicate that in the absence of nucleoside diphosphate, the enzyme is almost completely in the R state; that nucleoside triphosphates bind more tightly to the R than to the T state; that binding of nucleoside diphosphates to the regulatory site is very tight, but occurs only in the T state; and that competitive binding of nucleoside diphosphates at the catalytic sites is stronger in the T state than in the R state. Experiments conducted with varying total magnesium concentrations indicated that the magnesium complexes of nucleoside diphosphates are much stronger inhibitors than the free nucleotides, and that free nucleoside triphosphates are weakly inhibitory, probably competing with the magnesium complexes for binding at the catalytic sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1997

Impact of free vaccine and insurance status on physician referral of children to public vaccine clinics.

CONTEXT: Concerns about financial barriers to vaccination led to the development of the Vaccines for Children (VFC) program, which provides free vaccines to states for children who are uninsured, Medicaid eligible, or Native American or Native Alaskan. OBJECTIVE: To understand the effect of economic factors on physician likelihood of referring children to public vaccine clinics for immunizations and to evaluate the VFC program. DESIGN: A standardized survey was conducted in 1995 by trained personnel using computer-assisted telephone interviewing. SETTING AND PARTICIPANTS: A stratified random sample of family physicians, pediatricians, and general practitioners younger than 65 years who were in office-based practices across the United States. MAIN OUTCOME MEASURES: Likelihood of referral of a child to a health department for vaccination by child's insurance status and by the physician's receipt of free vaccines. RESULTS: Of the 1769 physicians with whom an interviewer spoke, 1236 participated. Most respondents (66%) were likely to refer an uninsured child to the health department for vaccination, whereas only 8% were likely to refer a child who had insurance that covers vaccination. The majority (58%) of physicians reported differential referral based on insurance status. Among physicians who received free vaccine supplies from the VFC program or elsewhere, 44% were likely to refer an uninsured child whereas 90% of those not receiving free vaccine were likely to refer the same child (P<.001). In regression analysis, the receipt of free vaccine supplies accounted for 24% of the variance in the likelihood to refer an uninsured child for vaccination. CONCLUSIONS: Physicians receiving free vaccine supplies report being less likely to refer children to public clinics for vaccinations.

Child↗
PubMed2001

Effect of preferred volume setting on speech audibility in different hearing aid circuits.

This study compared preferred volume setting for linear peak clipping, compression limiting, and wide dynamic range compression (WDRC) amplification and quantified speech audibility at the preferred volume setting for each amplification type. Ten listeners with mild-to-moderate hearing loss were fitted monaurally with a behind-the-ear hearing aid programmed sequentially with WDRC, compression limiting, and linear peak clipping amplification. Speech was presented in quiet and in noise at a range of input levels. In each condition, the listener adjusted the volume for maximum clarity. Signal levels were measured using a probe microphone system. There was no significant difference in speech audibility between amplification strategies for any speech level regardless of the presence or absence of background noise. These results imply that the improved audibility advantage of WDRC over linear amplification demonstrated in controlled environments may not be maintained in situations where the hearing aid wearer controls the volume.

Adult↗
PubMed2002

Kilovision: thermal modeling of a kilovoltage x-ray source integrated into a medical linear accelerator.

The thermal and thermo-mechanical (fatigue) properties of a stationary-anode kilovoltage x-ray source that can be integrated into the head of a medical linear accelerator have been modeled. A finite element program has been used to model two new target designs. The first design makes minor modifications to the existing target assembly of a Varian medical linear accelerator, while the second design adds an additional cooling tube, changes the target angle, and uses a tungsten-rhenium alloy rather than tungsten as the kilovoltage target material. The thermal calculations have been used to generate cyclic stress/strain values from which estimates of fatigue in the target designs have been made. Both kilovoltage and megavoltage operation have been studied. Analysis of the megavoltage operation shows that there are only small differences in the thermal and fatigue characteristics after the target assembly is modified to include a kilovoltage target. Thus, megavoltage operation should not be compromised. The first kilovoltage target design can handle a 900 W heat load (e.g., 120 kVp, 7.5 mA, 2 x 2 mm2 source size); the heat load being limited by the temperature at the surface of the cooling tubes and mechanical fatigue at the surface of the target. The second design can handle a 1250 W heat load (e.g., 120 kVp, approximately 10.4 mA, 2 x 2 mm2 source size). Our calculations show that installation of a kilovoltage x-ray target is practical from thermal and thermo-mechanical perspectives.

Computer Simulation↗
PubMed1991

Method for studying arterial wave transmission effects on left ventricular function.

A technique for studying the real-time effects of arterial wave reflections on the performance of the isolated left ventricle was investigated. Real-time arterial loading of an isolated ferret heart with an asymmetric T-tube wave transmission model was obtained with the use of a multiprocessor computer control system and a volume control linear motor pump. The multiprocessor computer system was programmed to compute the instantaneous aortic flow from the instantaneous ventricular pressure. The time integral of the flow was used as a command to the linear motor pump to control the instantaneous ventricular volume. This loading system allowed the imposition of a wide variety of vascular impedances on the ventricle by changing the parameters of the asymmetric T-tube model.

Animals↗
PubMed1996

Implementation of linear and quadratic discriminant analysis incorporating costs of misclassification.

Discriminant analysis plays an important role in biological and medical research. In practice, standard linear and quadratic methods are often applied which assume equal costs of misclassification. However, there can be situations where misclassifications between certain groups may be more serious than between other groups. Such considerations can be taken into account by using classification methods which incorporate misclassification costs. The widely applied statistical packages BMDP, SAS, and SPSS do not offer the possibility of using unequal misclassification costs for discriminant analysis with more than two groups. In this paper a menu-driven, user-friendly PC program written in Borland Pascal is introduced which performs linear and quadratic discriminant analysis for g > or = 2 groups allowing for the incorporation of misclassification costs.

Bias↗
PubMed1994

Phosphorescence lifetime analysis with a quadratic programming algorithm for determining quencher distributions in heterogeneous systems.

A new method for analysis of phosphorescence lifetime distributions in heterogeneous systems has been developed. This method is based on decomposition of the data vector to a linearly independent set of exponentials and uses quadratic programming principles for x2 minimization. Solution of the resulting algorithm requires a finite number of calculations (it is not iterative) and is computationally fast and robust. The algorithm has been tested on various simulated decays and for analysis of phosphorescence measurements of experimental systems with descrete distributions of lifetimes. Critical analysis of the effect of signal-to-noise on the resolving capability of the algorithm is presented. This technique is recommended for resolution of the distributions of quencher concentration in heterogeneous samples, of which oxygen distributions in tissue is an important example. Phosphors of practical importance for biological oxygen measurements: Pd-meso-tetra (4-carboxyphenyl) porphyrin (PdTCPP) and Pd-meso-porphyrin (PdMP) have been used to provide experimental test of the algorithm.

Algorithms↗
PubMed1999

Development of a 3-D measurement and evaluation system for facial forms with a liquid crystal range finder.

A 3-D measurement and evaluation system for facial forms was developed with a liquid crystal range finder (LCRF). Its mechanical resolution was approximately/= 0.4 mm, and it was capable of measuring >30000 points from the entire facial surface in one second. An original program was developed to identify facial landmarks using not only linear distances, but also 3D-curvatures and discriminant analysis of the RGB data. With this program, the 3-D identification of anthropometrical points became possible with high accuracy. Due to the rapidity of the measuring apparatus and morphological evaluation system, it became possible to analyze the facial forms of infants such as cleft lip patients three dimensionally, without any sedation. Therefore, 97 normal infants (mean: 4.3 months of age) were measured and analyzed with this system. A cleft lip infant was measured and compared with the normal infants before and after cleft lip surgery, and the improved points and remaining problems were clearly recognized.

Cephalometry↗