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PubMed1999

EasyBound--a user-friendly approach to nonlinear regression analysis of binding data.

The introduction of non-linear regression analysis of data from pharmacological experiments has provided an enormous advantage in making it possible to analyze raw data without any mathematical transformation. However, the disadvantage has been the lack of computer programs with simple user interfaces and the ability to easily handle large amounts of data. With the aim to develop a light-weight and still powerful program we have written an application called EasyBound which is designed to be used with Microsoft Excel and hence takes advantage of the abilities of the spreadsheet application to handle large amounts of data. Focus has been on creating an easy-to-understand user interface. There are commercial programs available, but they tend to be very complex and difficult to grasp for inexperienced users. EasyBound displays original data, calculated results and graphs on the same sheet/page. The program fully implements the most powerful algorithms for non-linear regression analysis, giving results that are more accurate than using built-in iterative analysis functions of the spreadsheet application without compromising ease of use.

Algorithms↗
PubMed2005

Geographical variation of cerebrovascular disease in New York State: the correlation with income.

BACKGROUND: Income is known to be associated with cerebrovascular disease; however, little is known about the more detailed relationship between cerebrovascular disease and income. We examined the hypothesis that the geographical distribution of cerebrovascular disease in New York State may be predicted by a nonlinear model using income as a surrogate socioeconomic risk factor. RESULTS: We used spatial clustering methods to identify areas with high and low prevalence of cerebrovascular disease at the ZIP code level after smoothing rates and correcting for edge effects; geographic locations of high and low clusters of cerebrovascular disease in New York State were identified with and without income adjustment. To examine effects of income, we calculated the excess number of cases using a non-linear regression with cerebrovascular disease rates taken as the dependent variable and income and income squared taken as independent variables. The resulting regression equation was: excess rate = 32.075-1.22 x 10(-4)(income)+ 8.068x10(-10)(income2), and both income and income squared variables were significant at the 0.01 level. When income was included as a covariate in the non-linear regression, the number and size of clusters of high cerebrovascular disease prevalence decreased. Some 87 ZIP codes exceeded the critical value of the local statistic yielding a relative risk of 1.2. The majority of low cerebrovascular disease prevalence geographic clusters disappeared when the non-linear income effect was included. For linear regression, the excess rate of cerebrovascular disease falls with income; each 10,000 dollars increase in median income of each ZIP code resulted in an average reduction of 3.83 observed cases. The significant nonlinear effect indicates a lessening of this income effect with increasing income. CONCLUSION: Income is a non-linear predictor of excess cerebrovascular disease rates, with both low and high observed cerebrovascular disease rate areas associated with higher income. Income alone explains a significant amount of the geographical variance in cerebrovascular disease across New York State since both high and low clusters of cerebrovascular disease dissipate or disappear with income adjustment. Geographical modeling, including non-linear effects of income, may allow for better identification of other non-traditional risk factors.

Journal Article↗
PubMed2004

Identifying and accommodating statistical outliers when setting prospective payment rates for inpatient rehabilitation facilities.

OBJECTIVE: To demonstrate how a Bayesian outlier accommodation model identifies and accommodates statistical outlier hospitals when developing facility payment adjustments for Medicare's prospective payment system for inpatient rehabilitation care. DATA SOURCES/STUDY SETTING: Administrative data on costs and facility characteristics of inpatient rehabilitation facilities (IRFs) for calendar years 1998 and 1999. STUDY DESIGN: Compare standard linear regression and the Bayesian outlier accommodation model for developing facility payment adjustors for a prospective payment system. DATA COLLECTION: Variables describing facility average cost per case and facility characteristics were derived from several administrative data sources. PRINCIPAL FINDINGS: Evidence was found of non-normality of regression errors in the data used to develop facility payment adjustments for the inpatient rehabilitation facilities prospective payment system (IRF PPS). The Bayesian outlier accommodation model is shown to be appropriate for these data, but the model is largely consistent with the standard linear regression used in the development of the IRF PPS payment adjustors. CONCLUSIONS: The Bayesian outlier accommodation model is more robust to statistical outlier IRFs than standard linear regression for developing facility payment adjustments. It also allows for easy interpretation of model parameters, making it a viable policy alternative to standard regression in setting payment rates.

Bayes Theorem↗
PubMed1989

A modernity score for individuals in Melanesian society.

Assessment of individual modernity has considerable implications for the prevention of non-communicable disease in high-risk populations experiencing rapid modernization. A scoring system for the classification of the relative modernity of individuals in Melanesian society is described. The score consisted of eight components relating to area of origin, employment, length of employment, father's employment, education, years spent in an urban centre, housing and an increment determined by the score of the spouse of the individual. The score was used in surveys of non-communicable disease in Papua New Guinea in 1985 and was validated, in one of the three communities studied, by the independent assessment of two local informants. With the use of analysis of variance and linear regression, the score was shown to be associated with obesity in both sexes. An association was also shown with age by both techniques in females. In males, age and glucose tolerance were associated with the score when using analysis of variance, but not when applying linear regression. Only three components, father's employment, education and the spouse increment proved useful when the score was used as the dependent variable in the linear regression equation. The utility of the other components may have been constrained by the narrow distribution of their scores in the populations studied.

Adult↗
PubMed2003

Method comparison studies for prostate specific antigen and unconjugated estriol immunoassays.

OBJECTIVE: Method comparison studies were performed in order to move a semi-automated prostate specific antigen (PSA) immunoassay and a manual unconjugated estriol (uE3) immunoassay to an automated chemistry immunoassay analyzer. The results of the two method comparison studies are compared. DESIGN: Serum samples collected on patients with physician orders for PSA or uE3 were assayed by both methods. PSA samples were assayed on a Hybritech Tandem Photon ERA and on two Beckman Coulter Access instruments. UE3 samples were assayed by RIA and on two Beckman Coulter Access instruments. Linear regression analysis was performed on both sets of data and within-run precision and dilution studies were performed on the PSA Access method. SETTING: Clinical chemistry laboratory, West Virginia University Hospitals Inc, Morgantown WV. RESULTS: PSA linear regression analysis for the two methods (ERA and Access 1) were y = 1.0008x + 0.0393, r = 0.9976, SE = 0.1319, n = 37 and (ERA and Access 2), y = 1.0019x + 0.0486, r = 0.9964, SE = 0.1632, n = 37. Within-run precision studies for both Access instruments produced acceptable coefficient variations and dilution study results were in PSA reportable range. uE3 linear regression analysis for the two methods (RIA and Access 1) were y = 1.4105x - 0.3741, r = 0.8696, SE = 0.8330, n = 33 and (RIA and Access 2) were y = 1.315x - 0.2292, r = 0.8643, SE = 0.7964, n = 33. CONCLUSION: The results of the method comparison studies for PSA were acceptable and the automated PSA immunoassay method was adopted. The results of the uE3 comparison studies did not show good correlation; the automated method was not adopted.

Automation↗
PubMed2000

Prediction of bladder outlet obstruction in men with lower urinary tract symptoms using artificial neural networks.

PURPOSE: To evaluate the performance of a backpropagation artificial neural network (ANN) in the diagnosis of men with lower urinary tract symptoms (LUTS) and to compare its performance to that of a traditional linear regression model. MATERIALS AND METHODS: 1903 LUTS patients referred to the University Hospital Nijmegen between 1992 and 1998 received routine investigation, consisting of transrectal ultrasonography of the prostate, serum PSA measurement, assessment of symptoms and quality of life by the International Prostate Symptom Score (IPSS), urinary flowmetry with determination of maximum flow rate (Qmax), voided volume and post-void residual urine and full pressure flow studies (PFS). Using a three-layered backpropagation ANN with three hidden nodes, the outcome of PFS, quantified by the Abrams-Griffiths number (AG-number), was estimated based on all available non-invasive diagnostic test results plus patient age. The performance of the network was quantified using sensitivity, specificity and the area under the ROC-curve (AUC). The results of the neural network approach were compared to those of a linear regression analysis. RESULTS: Prostate volume, Qmax, voided volume and post void residual urine showed substantial predictive value concerning the outcome of PFS. Patient age, PSA-level, IPSS and Quality of life did not add to that prediction. Using a cut-off value in predicted and true AG-numbers of 40 cm. H2O, the neural network approach yielded sensitivity and specificity of 71% and 69%, respectively. The AUC of the network was 0.75 (standard error = 0.01). A linear regression model produced identical results. CONCLUSIONS: This study shows that at an individual level, the outcome of PFS cannot be predicted accurately by the available non-invasive tests. The use of ANNs, which are better able than traditional regression models to identify non-linear relations and complex interactions between variables, did not improve the prediction of BOO. Thus, if precise urodynamic information is considered important in the diagnosis of men with LUTS, PFS must be carried out. Both neural networks and regression analysis appear promising to identify patients who should undergo PFS, and those in whom PFS can safely be omitted. Furthermore, the ability of ANNs and regression models to predict treatment result should be evaluated.

Humans↗
PubMed2004

Clinimetric evaluation of the bath ankylosing spondylitis metrology index in a controlled trial of pamidronate therapy.

OBJECTIVE: The Bath Ankylosing Spondylitis Metrology Index (BASMI) is an index comprising 5 measures of spinal and hip mobility in AS that has been primarily validated in the setting of a physiotherapeutic intervention and has not been validated in relation to functional outcomes. Our aim was to validate the BASMI and its individual components in relation to a validated functional index, the Bath AS Functional Index (BASFI), and to assess its responsiveness in patients with AS receiving 60 or 10 mg pamidronate monthly for 6 months in a double blind, randomized, controlled trial. METHODS: AS patients were assessed with the BASMI and BASFI at baseline and 6 months. Two versions of the BASMI were evaluated: the original scoring was based on a 0-2 score for each measure, while a newer version scores each measure on a 0-10 scale. Paired t tests, effect sizes (ES; mean difference divided by baseline standard deviation), and standardized response means (SRM; mean difference divided by standard deviation of the difference) were used to assess responsiveness. A value > 0.5 was considered to reflect good responsiveness. Responsiveness was also examined by linear regression analysis adjusting for age, sex, disease duration, and baseline Bath AS Disease Activity Index (BASDAI) and BASFI. The contribution of the BASMI to the variance in the BASFI was assessed by hierarchical linear regression analysis, independent variables being entered in the following order: (1) age, sex, disease duration; (2) drug dose group; (3) baseline or change in the BASDAI; and (4) change in the BASMI. Pearson correlation coefficient analysis was also performed to examine the contribution of individual measures of the BASMI. A value > 0.6 was defined as indicative of a good correlation. RESULTS: Seventy AS patients completed 6 months of therapy [81% male, mean age 40.3 yrs (SD 9.7), disease duration 15 yrs (SD 9.5)]. The responsiveness of the BASMI was poor regardless of which version of the BASMI was used (ES = 0.26, SRM = 0.47 for the 60 mg dose group and using a 0-10 scoring system). Examination of the responsiveness of the individual components of the BASMI revealed significance for lumbar side flexion in the 60 mg dosing group (ES = 0.4, SRM = 0.43; p = 0.01) using the newer version of the BASMI (0-10 scoring) that was of similar responsiveness to the entire BASMI. Linear regression analysis showed no significant effects of age, sex, disease duration, baseline BASFI and BASDAI, or drug dose group on BASMI change scored using a 0-2 grading, but drug dose group had a significant effect on BASMI change scored using a 0-10 grading (p = 0.04). The correlation between changes in the BASMI and the BASFI was low, although significant when either version of the BASMI was examined (0.44 and 0.46 for the 0-2 and 0-10 scoring systems, respectively; p < 0.001). Of the individual components of the BASMI, a significant association was observed between changes in either cervical rotation or lumbar side flexion and changes in the BASFI (0.44 and 0.37, respectively; p < 0.01). After adjusting for age, sex, disease duration, the baseline BASDAI, and drug dose group, the BASMI added significantly to the variance in the BASFI (p < 0.001), but this was no longer significant once change in the BASDAI was added to the regression model. CONCLUSION: Responsiveness of the BASMI was poor with either scoring system. Lumbar side flexion was the most responsive of the BASMI components. Changes in the BASMI and its individual components did not correlate well with changes in functional outcomes.

Adult↗
PubMed2002

Cortical involvement in temporal reproduction: evidence for differential roles of the hemispheres.

Only few studies have addressed temporal processing for durations longer than 1 s, and even fewer studies have investigated cortical involvement in time perception, in particular temporal production and reproduction. The present study investigated temporal reproduction in healthy control subjects and patients with anterior or posterior cortical lesions in the left or right hemisphere, or with subcortical left-hemispheric lesions. The paradigm involved presentation of either auditory or visual stimuli of 10 different standard intervals ranging from 1 to 5.5 seconds duration. Participants were required to reproduce the duration of a stimulus. Our results show that: (1) temporal reproduction across this temporal range can be better described with two separate linear regressions (bilinear approach) than with one single linear regression, thus contrasting the scalar timing concept; (2) that patients can, regardless of the hemisphere lesioned, perform reproductions of durations smaller than 2-3 s with reasonable accuracy; and (3) that patients with right-hemispheric lesions appear to be impaired in reproductions of stimuli longer than 2-3 s. Since attention appeared not to be impaired in the patients tested, the findings suggest that the integrity of the right hemisphere seems to be critical for temporal reproduction of intervals longer than 2-3 s.

Adult↗
PubMedDate not supplied

On heteroaromaticity of nucleobases. Bond lengths as multidimensional phenomena.

Three hundred and nine carbon-carbon, carbon-nitrogen, and carbon-oxygen pi-bond lengths in high precision crystal structures of 31 purine and pyrimidine nucleobases were related to the Pauling pi-bond order, its analogues corrected to crystal packing effects, the numbers of non-hydrogen atoms around the bond, and the sum of atomic numbers of the bond atoms. Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) demonstrated that the bond lengths in the nucleobases are three-dimensional phenomenon, characterized by nine distinct classes of bonds. Bond lengths predicted by Linear Regression models, Pauling Harmonic Potential Curves, Multiple Linear Regression, Principal Component, and Partial Least Squares Regression were compared to those calculated by molecular mechanics, semiempirical, and ab initio methods using PCA-HCA procedure on the calculated bond lengths, statistical parameters, and structural aromaticity indices. Incorporation of crystal packing effects into bond orders makes multivariate models to be competitive to semiempirical results, while further improvement of quantum chemical calculations can be achieved by geometry optimization of molecular clusters.

Databases, Factual↗
PubMedDate not supplied

Analysis of simple sequence repeats (SSRs) in wild barley from the Fertile Crescent: associations with ecology, geography and flowering time.

Wild barley, Hordeum spontaneum C. Koch, is the progenitor of cultivated barley, Hordeum vulgare. The centre of diversity is in the Fertile Crescent of the Near East, where wild barley grows in a wide range of conditions (temperature, water availability, day length, etc.). The genetic diversity of 39 wild barley genotypes collected from Israel, Turkey and Iran was studied with 33 SSRs of known map location. Analysis of molecular variance (AMOVA) was performed to partition the genetic variation present within from the variation between the three countries of origin. Using classification tree analysis, two (or three) specific SSRs were identified which could correctly classify most of the wild barley genotypes according to country of origin. Associations of SSR variation with flowering time and adaptation to site-of-origin ecology and geography were investigated by two contrasting statistical approaches, linear regression based on SSR length variation and linear regression based on SSR allele class differences. A number of SSRs were significantly associated with flowering time under four different growing regimes (short days, long days, unvernalised and vernalised). Most of the associations observed could be accounted for by close linkage of the SSR loci to earliness per se genes. No associations were found with photoperiodic and vernalisation response genes known to control flowering in cultivated barley suggesting that different genetic factors may be active in wild barley. Novel genomic regions controlling flowering time in wild barley were detected on chromosomes 1HS, 2HL, 3HS and 4HS. Associations of SSRs with site-of-origin ecological and geographic data were found primarily in genomic regions determining plant development. This study shows that the analyses of SSR variation by allele class and repeat length are complementary, and that some SSRs are not necessarily selectively neutral.

Alleles↗
PubMed2005

A noninvasive estimation of mixed venous oxygen saturation using near-infrared spectroscopy by cerebral oximetry in pediatric cardiac surgery patients.

BACKGROUND: Near-infrared spectroscopy (NIRS) is a noninvasive optical monitor of regional cerebral oxygen saturation (rSO2). The aim of this study was to validate the use of NIRS by cerebral oximetry in estimating invasively measured mixed venous oxygen saturation (SvO2) in pediatric postoperative cardiac surgery patients. METHODS: Twenty patients were enrolled following cardiac surgery with intraoperative placement of a pulmonary artery (PA) or superior vena cava (SVC) catheter. Five patients underwent complete biventricular repair--complete atrioventricular canal (n=3) and other (n=2). Fifteen patients with functional single ventricle underwent palliative procedures--bidirectional Glenn (n=11) and Fontan (n=4). Cerebral rSO2 was monitored via NIRS (INVOS 5100) during cardiac surgery and 6 h postoperatively. SvO2 was measured from blood samples obtained via an indwelling PA or SVC catheter and simultaneously correlated with rSO2 by NIRS at five time periods: in the operating room after weaning from cardiopulmonary bypass, after sternal closure, and in the CICU at 2, 4, and 6 h after admission. RESULTS: Each patient had five measurements (total=100 comparisons). SvO2 obtained via an indwelling PA or SVC catheter for all patients correlated with rSO2 obtained via NIRS: Pearson's correlation coefficient of 0.67 (P<0.0001) and linear regression of r2=0.45 (P<0.0001). Separate linear regression of the complete biventricular repairs demonstrated an r=0.71, r2=0.50 (P<0.0001). Bland-Altman analysis showed a bias of +3.3% with a precision of 16.6% for rSO2 as a predictor of SvO2 for all patients. Cerebral rSO2 was a more accurate predictor of SvO2 in the biventricular repair patients (bias -0.3, precision 11.8%), compared with the bidirectional Glenn and Fontan patients. CONCLUSIONS: Regional cerebral oximetry via NIRS correlates with SvO2 obtained via invasive monitoring. However, the wide limits of agreement suggest that it may not be possible to predict absolute values of SvO2 for any given patient based solely on the noninvasive measurement of rSO2. Near-infrared spectroscopy, using the INVOS 5100 cerebral oximeter, could potentially be used to indicate trends in SVO2, but more studies needs to be performed under varying clinical conditions.

Brain Chemistry↗
PubMed1982

The information content from renal biopsy in systemic lupus erythematosus.

We analyzed data for the 12-month period after renal biopsy was done in 130 patients with systemic lupus erythematosus to examine whether renal biopsy provides useful information on the nephritis of systemic lupus erythematosus beyond that clinically available. A stepwise linear regression analysis was used to construct a linear before biopsy model that predicted the change in renal function 12 months after biopsy. The model included serum creatinine, patient age, 24-hour urine protein, a laboratory index of renal activity, antibodies to DNA, urinalysis protein, change in inverse creatinine from 6 weeks before biopsy, and urine light chain protein, and had a squared multiple correlation coefficient (R2) of 0.246. Four prospectively chosen renal biopsy variables (glomerular cell counts, percent of sclerotic glomeruli, percent of glomeruli with crescents, and interstitial fibrosis) resulted in a 0.079 improvement in R2 (p less than or equal to 0.012). Both the percent glomerular sclerosis (p less than or equal to 0.0032) and subendothelial deposits shown by electron microscopy (p less than or equal to 0.0026) added significantly to the predictive power of the before biopsy model. Histologic classification did not add significantly to the before biopsy model. The renal biopsy information increased the power of a linear regression model to predict the effect of 12 months of treatment of active lupus nephritis.

Adult↗
PubMed1999

Intimal-medial thickness of the common carotid arteries and lower limbs atherosclerosis in the elderly.

BACKGROUND: In the present study, the authors consider the possible association between intimal-media thickness of the common carotid arteries and lower limb atherosclerosis, in a group of elderly patients; the authors also consider the presence of cardiovascular risk factors. METHODS: B-mode ultrasound measurement of the intimal-media thickness of the common carotid arteries was performed on 80 subjects. Lower limbs atherosclerosis was defined as the presence of intermittens claudicatio and/or ankle-arm index < 0.9. Baseline clinic examination and blood tests were performed in all subjects to consider the presence of cardiovascular risk factors. Linear regression analysis was used to assess the linear relationship between intimal-media thickness of the common carotid arteries and lower limb atherosclerosis. RESULTS: Linear regression analysis showed a statistical association between increased values of intimal-media thickness of the common carotid arteries and lower limb atherosclerosis. Sixty-four (80%) subjects presented one or more associated cardiovascular risk factors. CONCLUSIONS: The results of the the present study confirm that intimal-media thickness of the common carotid arteries is a marker for the identification of generalized atherosclerosis and may be useful for the identification of subjects, even at early stages, at risk of cardiovascular diseases.

Aged↗
PubMed1987

Simultaneous comparison of three noninvasive oximeters in healthy volunteers.

Noninvasive monitoring of arterial hemoglobin oxygen saturation (SaO2) from the Nellcor N-100 and the Ohmeda-Biox 3700 pulse oximeters were compared with SaO2 measured simultaneously by the Hewlett-Packard 47201A ear oximeter. A total of 868 pairs of data points ranging in saturation from 55-100% were obtained from 31 healthy adult volunteers of different ages, sex, skin pigmentation, height, weight, hematocrit, and smoking habits. Steady state and rapidly changing hypoxic conditions were achieved by varying the inspired O2 concentration between 10 and 100%. Measurements were analyzed by means of linear regression. The equations for the best fitted linear regression line between the Nellcor and the Ohmeda-Biox pulse oximeters as compared to the reference Hewlett-Packard ear oximeter readings were Y = 0.92X + 7.45 and Y = 1.10X - 10.73, respectively. Our study showed that despite a very close correlation among these three oximeters (r = 0.98), when compared to the Hewlett-Packard ear oximeter, the Nellcor pulse oximeter overestimates SaO2 by 2-4%, whereas the Ohmeda-Biox pulse oximeter underestimates SaO2 by 3-6% for SaO2 levels between 70 and 55%.

Adult↗
PubMed1994

Distribution function of transit times in the human pulmonary circulation.

The distribution function of pulmonary transit times (fPTT) defines contact time between blood and vascular bed, which affects gas exchange and endothelial metabolic functions. This study was undertaken to assess effects of abnormal pulmonary inflow (PPA) and outflow pressures (PLA) on fPTT. Three groups were studied: five patients with elevated PLA and passive pulmonary hypertension (LVD-Ab), eight with normal PLA (LVD-Nl), and six with pulmonary disease and various levels of PPA (PD). Empirical complex exponential functions were convoluted on right and left ventricular indicator-dilution curves to derive fPTT; mean transit time (Mo1), standard deviation (Sm2), and cube root of the third moment about Mo1 (Sm3) were calculated by standard equations. A single linear regression of Sm3 and Sm2 on Mo1 was observed for all patients, regardless of disease process. Inverse relations between Mo1, Sm2, and Sm3 and blood flow were highly significant, but dispersion volumes (DV = Mo1 x flow) were higher in patients with elevated PPA. Significant linear regressions of fPTT parameters on PPA, derived in LVD-Nl and LVD-Ab patients, failed to predict Mo1, Sm2, and Sm3 for the PD group, whereas linear regressions on PLA accurately predicted Mo1, Sm2, and Sm3 in the PD group. Relations between fPTT parameters and PLA were equally well fit by exponential equations in all 19 patients, consistent with an asymptotic pressure-volume relation of distensible vessels. Microvascular pressure (PMV), combining PPA and PLA, was not a better predictor of fPTT parameters in LVD-NL and LVD-Ab patients but provided a slightly closer estimate of relative dispersion and skewness in PD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Characterization and quantification of the return map of RR intervals by Pearson coefficient in patients with acute myocardial infarction.

The return map is the plot that displays the relationship between a point and its consecutive point in a time series. This study tried to characterize and quantify the return map of RR intervals (RRI) in subjects with patent coronary arteriogram and in patients with acute myocardial infarction (AMI) by using some parameters of linear regression between RRI(n+1) and RRI(n), and compared the newly introduced parameters with the time- and frequency-domain indices of heart rate variability (HRV) obtained from the same RRI. Three quantitative measures were introduced to quantify the return map of RRI: the Pearson coefficient, slope and Y-intercept of linear regression between RRI(n+1) and RRI(n). We found that the Pearson coefficient was almost identical to the slope of linear regression, and correlated significantly and negatively with Y-intercept in controls and patients with AMI. The Pearson coefficient and the slope in patients with AMI were significantly larger while the Y-intercept was significantly smaller than those of controls. The Pearson coefficient was also found to correlate significantly and negatively with the indices of vagal modulation and positively with the indices of sympatho-vagal balance and rennin-angiotensin-aldosterone modulation in both normal controls and patients with AMI. Our results suggested that the return map of RRI could be characterized and quantified by Pearson coefficient, which was related to the autonomic nervous modulation of the subject.

Aged↗
PubMed1997

Urinary excretion of unmetabolized and phase II conjugates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in humans: relationship to cytochrome P4501A2 and N-acetyltransferase activity.

Cooking meat, fish, or poultry at high temperature gives rise to heterocyclic aromatic amines (HAAs), which may be metabolically activated to mutagenic or carcinogenic intermediates. The enzymes cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) are principally implicated in such biotransformations. We have determined the relationship between the activity of these two enzymes and the urinary excretion of unmetabolized and Phase II conjugates of the two HAAs MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in individuals fed a uniform diet containing high-temperature cooked meat. The subjects in the study ate meat containing known amounts of MeIQx and PhIP, and urine collections were made 0-12 and 12-24 h after a meal. MeIQx and PhIP were measured in urine after acid treatment that quantitatively hydrolyzes the Phase II conjugates to the respective parent amine. The extracts containing the HAAs were purified by immunoaffinity chromatography and analyzed by liquid chromatography using electrospray ionization-tandem mass spectrometry. The MeIQx content in the 0-12 h urine increased after acid hydrolysis by a factor of 3-21-fold. After acid treatment, the total amount of MelQx (unmetabolized plus the N2-glucuronide and sulfamate metabolites) excreted in the 0-12 h urine was 10.5 +/- 3.5% (mean +/- SD) of the dose, whereas the total amount of PhIP [unmetabolized plus acid-labile conjugate(s)] in the 0-12 h period was 4.3 +/- 1.7% (mean +/- SD) of the dose. The total amount of PhIP in the 12-24 h urine after acid treatment was 0.9 +/- 0.4% (mean +/- SD) of the dose. Linear regression analysis of the amounts of MeIQx and PhIP excreted in the 0-12 h period expressed as a percentage of the ingested dose, for all subjects, gave a low but significant correlation (r = 0.37, P = 0.005). Linear regression analyses showed that lower total MeIQx (unmetabolized plus the N2-glucuronide and sulfamate metabolites) in urine was associated with higher CYP1A2 activity, whereas total PhIP (unmetabolized plus conjugated) in urine showed no association to CYP1A2 activity. These results indicate that in humans, MeIQx metabolism and disposition are more strongly influenced by CYP1A2 activity than are those of PhIP. Linear regression analysis found no association between NAT2 activity and the levels (unmetabolized plus acid-labile conjugates) of MeIQx or PhIP excreted in urine.

Animals↗
PubMed1997

Radiation effects on dopamine and norepinephrine.

PURPOSE: Radiation sterilization is becoming increasingly popular for the sterilization of many pharmaceutical products. We have investigated the gamma radiation induced effects on dopamine and norepinephrine by ESR spectroscopy. RESULTS AND DISCUSSION: Equations to describe the evolution of the ESR curves versus doses and time of storage are presented. Linear regression is, for dopamine hydrochloride, applicable for doses ranging from 10 to 25 kGy. Since the radiation dose selected must always be based upon the bioburden of the products and the degree of sterility required, doses in the range 10-25 kGy could be investigated and linear regression would appear to be the least expensive route to follow and gives good results. The comportment of noradrenaline bitartrate is more complex and the use of linear regression would appear more hazardous especially for low doses. For doses higher than 25 kGy, a more general equation is required. Power function using only 2 parameters could give good results but must be validated. Decay kinetics for radicals versus storage were considered. Non-homogeneous kinetics with time dependent rate constant and bi-exponential function appeared valid to reproduce the decay of radicals for, respectively, dopamine and norepinephrine. CONCLUSIONS: It is worth noting that, at present, ESR is the only technique which proved to be suitable for identification and quantification purposes in irradiated pharmaceuticals. Moreover, other features such as sensitivity, precision, ease and non-destructive readout make ESR superior to other proposed analytical techniques.

Dopamine↗