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At least 1,351 records · Page 75Linked to original sources
PubMed2006

Pharmacological conversion of persistent atrial fibrillation into sinus rhythm with oral pilsicainide: pilsicainide suppression trial for persistent atrial fibrillation II.

BACKGROUND: The present study was conducted to determine the antiarrhythmic efficacy and safety of oral pilsicainide, a class Ic antiarrhythmic drug, in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS: One hundred and eight patients (mean age, 58.9 years) with AF lasting >or=48 h and or=3 weeks prior to the study enrolment or after verification of the absence of left atrial thrombi by transesophageal echocardiography. After 2 weeks of treatment, an electrocardiogram was recorded to determine whether sinus rhythm was restored. Sinus rhythm was restored in 22.4% of patients treated with pilsicainide and in 2% treated with placebo (p=0.002). Cardioversion was less likely to occur with oral pilsicainide when the AF duration exceeded 2 months or if the left atrial diameter exceeded 45 mm. There was no significant difference in the adverse cardiovascular event rate between the pilsicainide- and placebo-treated groups. One patient in the pilsicainide group developed an atrial flutter without any hemodynamic deterioration. CONCLUSION: A 2-week oral administration of pilsicainide is well tolerated and moderately effective in converting persistent AF into sinus rhythm.

Administration, Oral↗
PubMed2002

Bias in risk estimation: application to Down's syndrome screening.

In this paper we consider the bias associated with parametric estimation of a univariate or bivariate Gaussian density, and also the induced bias when these Gaussian densities are used to determine a likelihood ratio. Algebraic approximations are derived that accurately predict the relative biases obtained, verification being achieved by a simulation exercise. The expressions confirm that when estimating a univariate Gaussian density there are four Z-scores for which there is zero bias and that relative bias increases rapidly beyond two standard deviations from the mean. The results are then extended to determine approximate confidence intervals for both the true density and the likelihood ratio. A simulation exercise confirms that the derived 95 per cent confidence intervals have coverage that ranges from 94 to 97 per cent. The results are applied to a Down's syndrome screening programme where 95 per cent confidence intervals are established for a woman's posterior odds of carrying a Down's foetus. It is shown that patients with similar posterior odds can give rise to confidence intervals for their true posterior odds that have very different widths, thus emphasizing that not all risks are of equal quality.

Adult↗
PubMed2004

Performance of electronic portal imaging devices (EPIDs) used in radiotherapy: image quality and dose measurements.

The aim of our study was to compare the image and dosimetric quality of two different imaging systems. The first one is a fluoroscopic electronic portal imaging device (first generation), while the second is based on an amorphous silicon flat-panel array (second generation). The parameters describing image quality include spatial resolution [modulation transfer function (MTF)], noise [noise power spectrum (NPS)], and signal-to-noise transfer [detective quantum efficiency (DQE)]. The dosimetric measurements were compared with ionization chamber as well as with film measurements. The response of the flat-panel imager and the fluoroscopic-optical device was determined performing a two-step Monte Carlo simulation. All measurements were performed in a 6 MV linear accelerator photon beam. The resolution (MTF) of the fluoroscopic device (f 1/2 = 0.3 mm(-1)) is larger than of the amorphous silicon based system (f 1/2 = 0.21 mm(-1)), which is due to the missing backscattered photons and the smaller pixel size. The noise measurements (NPS) show the correlation of neighboring pixels of the amorphous silicon electronic portal imaging device, whereas the NPS of the fluoroscopic system is frequency independent. At zero spatial frequency the DQE of the flat-panel imager has a value of 0.008 (0.8%). Due to the minor frequency dependency this device may be almost x-ray quantum limited. Monte Carlo simulations verified these characteristics. For the fluoroscopic imaging system the DQE at low frequencies is about 0.0008 (0.08%) and degrades with higher frequencies. Dose measurements with the flat-panel imager revealed that images can only be directly converted to portal dose images, if scatter can be neglected. Thus objects distant to the detector (e.g., inhomogeneous dose distribution generated by a modificator) can be verified dosimetrically, while objects close to a detector (e.g., a patient) cannot be verified directly and must be scatter corrected prior to verification. This is justified by the response of the flat-panel imaging device revealing a strong dependency at low energies.

Equipment Failure Analysis↗
PubMed1993

Fertility in cryptorchidism. Does treatment make a difference?

The testis which remains nonscrotal beyond puberty will not produce sperm. While much of the data presented imply that therapy of cryptorchidism during childhood will decrease the likelihood of infertility, the available data do not substantiate this. There are also inadequate data to indicate whether treatment at very young ages in childhood decreases the risk of infertility. In fact, it is not clear that fertility rates among males who were unilaterally cryptorchid is different than that of the unaffected male population! Therefore, verification is needed to determine whether or not fertility is decreased in cryptorchidism. Paternity is a better index for verification than sperm counts since it is known that men with subnormal sperm counts may have normal paternity rates. Such verification using paternity may require more than fathering a child, such as the age of the father at the birth of the first child, length of marriage or partnership before birth of the first or subsequent children, or duration of intercourse without contraception to birth. Because of the multiple etiologies of the cryptorchid state, factors such as the relative size of the testis before treatment, and the position of the testis and the histology of the testis need to be considered since the small testis, the abdominal testis and the testis with the most histologic changes would appear to be at the greatest risk for defects in spermatogenesis. Until these data become available, most physicians are likely to recommend treatment of the undescended testis when detected if the child is older than six months. However, it must be remembered that there are no data to indicate benefit of early treatment. Before treatment is initiated, the physician must be careful to rule out a retractile testis. Also, the possibility of ascent of the testis which may occur during midchildhood, the age of physiologically normal hypogonadotropism, must be remembered. The testis which was previously normally descended but resides much of the time during midchildhood years within the inguinal canal may be a variant of normal and not require therapy. The approach to the patient with cryptorchidism must involve a careful history and repeated examinations looking for a cause and for accurate position of the testis. If the testis can be moved from the nonscrotal position into the scrotum, the potential function of the testis should not be harmed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed2000

Megavoltage CT imaging as a by-product of multileaf collimator leakage.

In addition to their potential for the delivery of highly conformal radiation therapy treatments, tomotherapeutic treatments also feature increased potential for verification. For example, megavoltage CT allows one to use the megavoltage linac to generate tomographic images of the patient in the treatment position. This is typically done before or after radiation therapy treatments. However, it is also possible to collect MVCT images entirely during the treatment itself. This process utilizes the leakage radiation through the closed leaves of the Nomos MIMiC MLC, along with slight inefficiencies in treatment delivery, to generate MVCT images during treatment that require neither additional time nor dose. The image quality is limited, yet sufficient to see a patient's external boundary, density differences over 8% for 25.0 mm objects and resolutions of 3.0 mm for high-contrast objects. Such images can potentially be viewed during treatment, used to flag additional CT immediately after the treatment and provide a representation of the patient's exact position during treatment for use with dose reconstruction.

Humans↗
PubMed2003

Lateralization of prefrontal activity during episodic memory retrieval: evidence for the production-monitoring hypothesis.

We propose a new hypothesis concerning the lateralization of prefrontal cortex (PFC) activity during verbal episodic memory retrieval. The hypothesis states that the left PFC is differentially more involved in semantically guided information production than is the right PFC, and that the right PFC is differentially more involved in monitoring and verification than is the left PFC. This "production-monitoring hypothesis" differs from the existing "systematic-heuristic hypothesis," which proposes that the left PFC is primarily involved in systematic retrieval operations, and the right PFC in heuristic retrieval operations. To compare the two hypotheses, we measured PFC activity using positron emission tomography (PET) during the performance of four episodic retrieval tasks: stem cued recall, associative cued recall, context recognition (source memory), and item recognition. Recall tasks emphasized production processes, whereas recognition tasks emphasized monitoring processes. Stem cued recall and context-recognition tasks underscored systematic operations, whereas associative cued recall and item-recognition tasks underscored heuristic operations. Consistent with the production-monitoring hypothesis, the left PFC was more activated for recall than for recognition tasks and the right PFC was more activated for recognition than for recall tasks. Inconsistent with the systematic-heuristic hypothesis, the left PFC was more activated for heuristic than for systematic tasks and the right PFC showed the converse result. Additionally, the study yielded activation differences outside the PFC. In agreement with a previous recall/recognition PET study, anterior cingulate, cerebellar, and striatal regions were more activated for recall than for recognition tasks, and the converse occurred for posterior parietal regions. A right medial temporal lobe region was more activated for stem cued recall and context recognition than for associative cued recall and item recognition, possibly reflecting perceptual integration. In sum, the results provide evidence for the production-monitoring hypothesis and clarify the role of different brain regions typically activated in PET and functional magnetic resonance imaging (fMRI) studies of episodic retrieval.

Adult↗
PubMed1981

Racial variations in vision.

This study determined the distributions of uncorrected visual acuity and of refractive error in representative groups of Australian Aborigines and Australians of European origin aged 20-30 years. The methodology used in this study and its verification are described in detail. As a group, the Aborigines have significantly better visual acuity than the Europeans. This was true for both monocular and binocular vision. Some Aborigines have acuities below the previous postulated threshold levels. Aborigines as a group also have the previous postulated threshold levels. Aborigines as a group also have less myopia--in particular, less high myopia--and less astigmatism than Europeans. The mean refraction for Aborigines is about half a diopter more hypermetropic than that for Europeans, although there is not an excess of high hypermetropia in Aborigines. The lack of high refractive errors suggests that the Aborigines may not possess the genes that cause abnormal axial lengths usually associated with high refractive errors in Europeans. The superior vision of the Aborigines persisted, however, when comparing groups which were essentially emmetropic. Therefore, it appears to be a true racial difference which is not explicable on the grounds of variation in refractive error but may result from finer retinal organization or better cerebral integration of visual stimuli.

Australia↗
PubMed2004

Vocal efficiency measurements in subjects with vocal polyps and nodules: a preliminary report.

Vocal efficiency is a quantitative measure of the ability of the larynx to convert subglottal power to acoustic power. On the basis of the scant previous literature and clinical intuition, we tested the hypothesis that vocal efficiency, as an indicator of the functional status of the larynx, is abnormally reduced in persons with vocal nodules and polyps. Because the most difficult aspect of obtaining measures of vocal efficiency has been the determination of subglottal pressure, we applied a noninvasive airflow interruption technique for this purpose. Subjects with normal voices (n = 22), vocal polyps (n = 14), and vocal nodules (n = 16) phonated at different intensities into a mask connected by way of piping to a flow meter, a pressure transducer, and an acoustic microphone. Inflation of a balloon-type valve located within the piping provided interruption of phonation. The intraoral pressure plateau occurring during flow interruption was used to estimate subglottal pressure. Subglottal power and acoustic power were determined, and their quotient provided a measure of vocal efficiency. The vocal efficiency in the normal subjects averaged 1.15 x 10(-5) at 70 dB, 3.17 x 10(-5) at 75 dB, 7.52 x 10(-5) at 80 dB, and 1.41 x 10(-4) at 85 dB. The vocal efficiency in the patients with vocal polyps averaged 3.62 x 10(-6) at 70 dB, 8.34 x 10(-6) at 75 dB, 2.10 x 10(-5) at 80 dB, and 4.26 x 10(-5) at 85 dB. The vocal efficiency in the patients with vocal nodules averaged 4.32 x 10(-6) at 70 dB, 1.57 x 10(-5) at 75 dB, 4.26 x 10(-5) at 80 dB, and 8.34 x 10(-5) at 85 dB. As compared to the normal subjects, the patients with laryngeal polyps or vocal nodules had significantly reduced vocal efficiency. These results provide quantitative verification of the clinical impression of inefficient phonation in patients with mass lesions of the vocal folds.

Adult↗
PubMedDate not supplied

Central venous catheter placement using the ECG-guided Cavafix-Certodyn SD catheter.

STUDY OBJECTIVE: To evaluate the clinical use of a new ECG-guided central venous catheter with regard to positioning in the superior vena cava (SVC). DESIGN: Prospective study. SETTING: Operating rooms of a university hospital and a general hospital. PATIENTS: 89 elective and emergency adult surgical patients requiring central venous catheterization perioperatively. INTERVENTIONS: We performed ECG-guided placement of the central venous catheter from several insertion sites. After we observed an intra-atrial p-wave (p-atriale), the catheter was withdrawn 3 cm back into the SVC. Postoperative anterior-posterior chest radiographs were performed for verification of tip localization. MEASUREMENTS AND MAIN RESULTS: In all 81 patients who exhibited a p-atriale that reverted to a normal-size p-wave (p-SVC) after withdrawal of the catheter 3 cm, the tip was located in the SVC or the SVC-right atrial junction on the chest radiograph. In 7 of the 8 cases without a p-atriale, the catheter tip was shown to be located at an incorrect position on the chest radiograph. The size of the p-atriale was always at least twice that of the p-SVC. CONCLUSIONS: Use of this wire-conducted intravascular ECG signal is a reliable tool for positioning the central venous catheter via various insertion sites. The technique proved to be an inexpensive, easy, and clear method. When a p-atriale is seen, uncomplicated insertions do not require radiologic guidance to control catheter tip position.

Adult↗
PubMed2003

Five-year follow-up of routine outpatient test turnaround time: a College of American Pathologists Q-Probes study.

CONTEXT: Timely reporting of outpatient tests can increase efficiency of care and improve customer satisfaction. OBJECTIVES: We conducted a survey in 2002 to determine how quickly hospital-based laboratories turned around routine requests for 3 common assays and compared the results with a similar survey conducted in 1997. DESIGN: One hundred eighteen laboratories prospectively recorded the collection-to-verification turnaround time for 9252 complete blood cell counts (CBCs), 8832 thyroid tests, and 9193 basic metabolic panels. RESULTS: The median facility reported all test results by 7:00 am of the weekday immediately after the date of specimen collection. The bottom 10% of institutions reported 99% of CBCs and basic metabolic panels within 1 day and 60% of thyroid tests within 1 day. The 65 institutions that participated in both the 1997 and 2002 surveys showed significant overall improvement in turnaround time for all 3 types of tests (P <.001). In 2002, federal institutions had significantly slower turnaround times than nonfederal institutions for CBC tests (P <.001), thyroid tests (P =.03), and basic metabolic panels (P <.001). Other demographic and practice variables were not associated with turnaround time. CONCLUSION: The turnaround time of routine outpatient tests appears to have improved between 1997 and 2002.

Blood Cell Count↗
PubMed2005

Evaluating the influence of setup uncertainties on treatment planning for focal liver tumors.

PURPOSE: A mechanism has been developed to evaluate the influence of random setup variations on dose during treatment planning. The information available for studying these factors shifts from population-based models toward patient-specific data as treatment progresses and setup measurements for an individual patient become available. This study evaluates the influence of population as well as patient-specific setup distributions on treatment plans for focal liver tumors. METHODS AND MATERIALS: Eight patients with focal liver tumors were treated on a protocol that involved online setup measurement and adjustment, as well as ventilatory immobilization. Summary statistics from these three-dimensional conformal treatments yielded individual and population distributions of position at initial setup for each fraction. A convolution model for evaluation of the influence of random setup variation on calculated dose distributions has been previously described and investigated for application to focal liver radiotherapy by our department. Individual patient doses based on initial setup positions were calculated by convolving the calculated dose distribution with an anisotropic probability distribution function representing the individual patient's random variations. A separate convolution using population-averaged random variations was performed. Individual beam apertures were then adjusted to provide plans that ensured proper dose to the clinical target volume following convolution with population distributions, as well as individual patient position uncertainty models. RESULTS: Individual patient setup distributions for the course of treatment had random setup variations (sigma) that ranged from 2.5 to 5.7 mm (left-right), 2.1 to 8.3 mm (anterior-posterior), and 4.1 to 10.8 mm (cranial-caudal). The population random components were 4.2 mm (left-right), 4.1 mm (anterior-posterior), and 7.0 mm (cranial-caudal) at initial setup. The initial static planned dose distribution overestimated the volume of liver irradiated to high doses, because inclusion of setup uncertainties generally blurred the resulting doses, shifting the higher-dose region of normal liver dose-volume histograms to lower doses. Furthermore, the population-based dose convolution tended to predict a higher risk of radiation damage to the liver (based on an in-house parameterization of the Lyman normal tissue complication probability model) than the individual patient calculations. For an individual plan, application of different individual random variations yielded change in effective volume differences with a 3% range. Plan adjustment to account for random setup variations generally resulted in a lower change in effective volume than initial planning using a planning target volume followed by calculation of delivered dose based on random offsets. CONCLUSION: This study hints at the factors that most strongly influence planning of liver treatments taking into account geometric variations. Given a setup verification methodology that rapidly reduces systematic offsets, the importance of realistic incorporation of geometric variations as an initial step in treatment planning, as well as possible plan refinement, is demonstrated.

Feasibility Studies↗
PubMed1999

Compliance with methodological standards when evaluating ophthalmic diagnostic tests.

PURPOSE: To draw attention to the importance of methodological standards when carrying out evaluations of ophthalmic diagnostic tests by reviewing the extent of compliance with these standards in reports of evaluations published within the ophthalmic literature. METHODS: Twenty published evaluations of ophthalmic screening/diagnostic tests or technologies were independently assessed by two reviewers for compliance with the following methodological standards: specification of the spectrum composition for populations used in the evaluation, analysis of pertinent subgroups, avoidance of work-up (verification) bias, avoidance of review bias, presentation of precision of results for test accuracy, presentation of indeterminate test results, and presentation of test reproducibility. RESULTS: Compliance ranged from just 10% (95%CI, 1%-32%) for presentation of test reproducibility data and avoidance of review bias to 70% (95%CI, 46%-88%) for avoidance of work-up bias and presentation of indeterminate test results. Only 5 of the 20 evaluations complied with four or more of the methodological standards and none with more than five of the standards. CONCLUSIONS: The evaluations of ophthalmic diagnostic tests discussed in this article show limited compliance with accepted methodological standards but are no worse than previously described for evaluations published in general medical journals. Adherence to these standards by researchers can improve the study design and reporting of evaluations of new diagnostic techniques. Limited compliance, combined with a lack of awareness of the standards among users of research evidence, may lead to the inappropriate adoption of new diagnostic technologies, with a consequent waste of health care resources.

Bias↗
PubMed1994

Dosimetric characteristics, air-kerma strength calibration and verification of Monte Carlo simulation for a new Ytterbium-169 brachytherapy source.

PURPOSE: Ytterbium-169 (169Yb) is a promising new isotope for brachytherapy with a half life of 32 days and an average photon energy of 93 KeV. It has an Ir-192-equivalent dose distribution in water but a much smaller half-value layer in lead (0.2 mm), affording improved radiation protection and customized shielding of dose-limiting anatomic structures. The goals of this study are to: (a) experimentally validate Monte Carlo photon transport dose-rate calculations for this energy range, (b) to develop a secondary air-kerma strength standard for 169Yb, and (c) to present essential treatment planning data including the transverse-axis dose-rate distribution and dose correction factors for a number of local shielding materials. METHODS AND MATERIALS: Several interstitial 169Yb sources (type 6) and an experimental high dose-rate source were made available for this study. Monte-Carlo photon-transport (MCPT) simulations, based upon validated geometric models of source structure, were used to calculate dose rates in water. To verify MCPT predictions, the transverse-axis dose distribution in homogeneous water medium was measured using a silicon-diode detector. For use in designing shielded applicators, heterogeneity correction factors (HCF) arising from small cylindrical heterogeneities of lead, aluminum, titanium, steel and air were measured in a water medium. Finally, to provide a sound experimental basis for comparing experimental and theoretical dose-rate distributions, the air-kerma strength of the sources was measured using a calibrated ion chamber. To eliminate the influence of measurement artifacts on the comparison of theory and measurement, simulated detector readings were compared directly to measured diode readings. The final data are presented in the format endorsed by the Interstitial Collaborative Working Group. RESULTS: The in-air calibration revealed that the air-kerma strength per unit activity (mCi), as quoted by the vendor, varied from 1.30 to 1.57 cGy.cm2/mCi.h depending on seed design. The maximum difference between measured and MCPT-simulated absolute diode readings on the transverse axis was less than 2%, indicating that MCPT accurately predicts dose rate in medium for brachytherapy sources in this energy range. Comparison of measured and simulated HCFs for each of the 16 different cylindrical heterogeneities demonstrated 1-3% agreement. The HCFs vary by as much as 200% with respect to distance and by as much as 48% as a function of disk diameter, showing that HCF is strongly dependent on heterogeneity location and lateral dimensions as well as thickness. The dose-rate constant for water medium was found to be 1.225 cGy/h per kerma unit air-strength and 1.962 cGy/h per unit mCi as measured by the vendor. CONCLUSION: Monte Carlo simulation is an accurate and powerful tool for dosimetric characterization of brachytherapy sources in this energy range. Thin lead foils produce shielding factors comparable to standard shielded applicators for 137Cs. Meaningful theoretical absolute dose calculations in brachytherapy require accurately implemented air-kerma strength standards.

Brachytherapy↗
PubMed1986

Verification of Fourier phase and amplitude values from simulated heart motion using a hydrodynamic cardiac model.

Using pusher-plate-type artificial hearts, changes in the degree of synchrony and stroke volume were compared to phase and amplitude calculations from the first Fourier component of individual-pixel time-activity curves generated from gated radionuclide images (RNA) of these hearts. In addition, the ability of Fourier analysis to quantify paradoxical volume shifts was tested using a ventricular aneurysm model by which the Fourier amplitude was correlated to known increments of paradoxical volume. Predetermined phase-angle differences (incremental increases in asynchrony) and the mean phase-angle difference calculated from RNAs showed an agreement of -7 degrees +/- 4.4 degrees (mean +/- SD). A strong correlation was noted between stroke volume and Fourier amplitude (r = 0.98; P less than 0.0001) as well as between the paradoxical volume accepted by the 'aneurysm' and the Fourier amplitude (r = 0.97; P less than 0.0001). The degree of asynchrony and changes in stroke volume were accurately reflected by the Fourier phase and amplitude values, respectively. In the specific case of ventricular aneurysms, the data demonstrate that using this method, the paradoxically moving areas may be localized, and the expansile volume within these regions can be quantified.

Fourier Analysis↗
PubMed1992

A personal computer based implementation of the maximum-likelihood method of analysis of electron microscope autoradiographs.

The maximum-likelihood (ML) method for the quantitative analysis of electron-microscopic autoradiographs has been shown to be substantially superior to the conventional crossfire (CF) method. It can generate reliable and accurate tracer concentration estimates with far fewer micrographs and produce valid estimates even at counts low enough to preclude the use of the crossfire method while eliminating the need for special ad hoc treatment of narrow membranous structures as well as the secondary verification of the tracer concentration estimates. Despite these significant advantages, the large computational requirements of the ML method has to date hampered its widespread use. In this paper, we present a new line-integration method that allows us to reduce the computational requirements of the ML method to a point where it becomes feasible to implement it on a small computer system of the type typically available to a laboratory user of EM autoradiography. We present the complete line-integration method for the particular case of EM autoradiography with tritium, and show how it can be adapted to other isotopes. We have constructed a software package that implements the complete maximum-likelihood method on the IBM PC class of machines using our line-integration method. Features of this software package which are of particular importance to the research community are device independence, which makes it usable with a large variety of currently available laboratory equipment, and easy portability of the software and data between different computer systems.

Algorithms↗
PubMed2003

Fcgamma receptor polymorphisms in relation to periodontitis.

OBJECTIVES: Evidence suggests functional relevance for polymorphisms in FcgammaR in relation to inflammatory and infectious diseases. The present aim was to investigate genetic polymorphisms in three FcgammaR in relation to susceptibility and severity of periodontitis. MATERIAL AND METHODS: The study population consisted of 68 periodontitis patients and 61 controls (Northern European Caucasian background, mean ages 44 and 42 years, respectively). Among the patients, 12 subjects were diagnosed with aggressive periodontitis (AgP) and 56 individuals were diagnosed with chronic periodontitis (CP). Radiographic bone levels were scored for all teeth in the patients. Subjects were typed for the following genes (alleles): FcgammaRIIa (R131 or H131), FcgammaRIIIa (V158 or F158) and FcgammaRIIIb (NA1 or NA2). RESULTS: Hardy-Weinberg equilibrium criteria were fulfilled for the different genotypes at the three genes investigated. The frequency of the FcgammaRIIIa-V158 allele in the patient population (53%) was higher than in the control group (39%) (OR 1.73 [1.06-2.85], p=0.034). The V158 carriage rate in AgP was even higher (63%). The frequency of the FcgammaRIIa-H131 allele in the total periodontitis population was 58%; for AgP this was 79%, compared with 51% in the control population (OR 3.68 [1.29-10.5], p=0.013). Also, the frequency of the FcgammaRIIa-H/H131 genotype was significantly higher in AgP patients than in controls (OR 9.07 [1.29-63.56], p=0.026, adjusted for smoking status and other potential confounders). Moreover, patients with the FcgammaRIIa-H/H131 genotype had more severe radiographic bone loss than patients with the other FcgammaRIIa genotypes. CONCLUSION: The current study of relative small sample size suggests that the FcgammaRIIa-H/H131 genotype may be a putative susceptibility and severity factor, and the FcgammaRIIIa-V158 allele a putative susceptibility factor for periodontitis in Northern European Caucasians. These results need further verification and the biological importance of these findings needs further investigation.

Acute Disease↗
PubMed1996

A research to develop a predicting system of mammalian subacute toxicity. I. Prediction of subacute toxicity using the biological parameters of acute toxicities.

Predicting equations of subacute toxicity were developed by analyzing rat acute and subacute toxicity data of 56 chemicals of various structures. Minimum or 10% effect level in acute or subacute toxicity was estimated as a "biological parameter". Good regression equations were established between the geometrical means ("combined parameters") of any two of the parameters of acute and subacute toxicities and introduction of log P to the equations improved the correlations with a statistically significant multiple regression coefficient. The lowest predicted effect level of the subacute toxicity, which is selected from the data calculated by the above several correlations, can predict the upper limit of the no observed effect level. In recent years, for research and development of new chemical substances, it becomes one of the important factors that these have a lower environmental load in nature. Eventually, it becomes essential to evaluate not only their acute effects on human or environments, but also their chronic influences when they are to be exposed for a long period of time, and the cost for such verification is becoming a breaking factor for research and development. Thus, the development of a new technique which estimates the environmental load of a chemical substance including toxic effects on human with lower cost is now being attempted. For example, the development of in vitro new alternative methods using cultured cells, the utilization of a data base or software which relates mammalian and environmental toxicities and so on are internationally carried forwards. As for the latter, quantitative structure-activity relationship (QSAR) techniques have been applied practically to decide appropriate toxicity tests needed for regulatory purposes by EPA/TSCA, ITC/TSCA and FDA/FDAA in the USA. In addition, it was concluded recently in a joint meeting of EU and US-EPA that the approach by QSAR techniques was useful to specify the new chemical substances which are to be required toxicological examinations. In these QSAR techniques, however, while there are some considerations about common mechanisms of toxicity among chemicals with a similar structure (Congeneric chemicals, Congeners) for establishing of correlation formulas, for chemicals with various structures (Non-congeneric chemicals, Non-congeners) there often lack such common considerations. In addition, biological or physiological factors which are basic toxic indices are often ignored. In a previous study, we researched acute and subacute oral toxicities of industrial common chemicals in rats and reported the followings; 1) their subacute toxicological spectrum in target organs/tissues and morphologic changes was very limited and specific, 2) the important targets were liver, kidneys, blood (spleen) and stomach and these are considered the sites of dominant exposure due to the kinetics of chemical substances, 3) the morphological changes were hepatocellular hypertrophy, deposition of substance in renal tubules, extramedullary hematopoiesis in spleen and mucous lesion in stomach, and these are implying adaptation such as induction of drug-metabolizing enzymes, overload to renal function, anemia from erythrocyte destruction, and direct reaction, respectively, 4) there seems to occur a series of direct and adaptive reactions to exclude the "foreign compounds" which do not show any specific biological activities, 5) it is also considered that there is a possibility to establish a correlation between toxicological findings or target organs/tissues of both acute and subacute toxicities by their continuity. Therefore, in the present study, a predicting equation of subacute (28-day repeated dose) toxicity is attempted to develop from acute (single dose) toxicity data by considering both common mechanisms and biological factors for non-congeneric industrial chemical substances.

Animals↗
PubMed1995

Stereoselective hydroxylation of norcamphor by cytochrome P450cam. Experimental verification of molecular dynamics simulations.

The stereoselectivity of cytochrome P450cam hydroxylation has been investigated with the enantiomerically pure substrate analog norcamphor. (1R)- and (1S)-norcamphor (> 92 enantiomeric excess) were characterized in the hydroxylation reaction with cytochrome P450cam with respect to the product profile, steady state kinetics, coupling efficiency, and free energy of substrate dissociation. The experimental results demonstrate regiospecificity that is enantiomer-specific and confirm our previously reported prediction that (1R)-norcamphor is hydroxylated preferentially at the 5-carbon and (1S)-norcamphor at the 6-carbon (Bass, M. B., and Ornstein, R. L. (1993) J. Comput. Chem. 14, 541-548); these simulation results are now compared with simulations involving a ferryl oxygen intermediate. Hydroxylation of (1R)-norcamphor was found at the 5-, 6-, and 3-carbons in a ratio of 65:30:5 (respectively), whereas (1S)-norcamphor was oxidized to produce a 28:62:10 ratio of the same products. With the exception of the regiospecificity, all of the reaction and physical parameters are similar for each enantiomer of norcamphor. These results show that the position of the carbonyl group on the hydrocarbon skeleton of norcamphor plays a role in determining the average orientation of this substrate in the active site and suggests that hydrogen bonding interactions can aid in directing the regiospecificity and stereospecificity of the hydroxylation reaction catalyzed by cytochrome P450cam.

Binding Sites↗