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Adsorptive stripping voltammetric behaviour of azomethine group in pyrimidine-containing drugs.

The stripping voltammetric behaviour of buspirone hydrochloride (BUS) and piribedil (PIR), as models of pyrimidine-containing compounds, was studied using a hanging mercury drop electrode (HMDE). A sensitive adsorptive stripping voltammetric method for determination of such drugs is described. The voltammetric peaks were obtained at -1.23 and -1.22 V for BUS and PIR. respectively, which correspond to the reduction of the azomethine group of pyrimidine ring in Britton-Robinson buffer (pH 7). Factors such as pH of supporting electrolyte, accumulation potential and time and instrumental parameters were optimized. Calibration plots and regression data validation, accuracy, precision, limits of detection, limits of quantification, and other aspects of analytical merit are presented. The applicability of the method was evaluated through determination of BUS and PIR in tablet dosage forms. A preliminary study of the analysis of plasma samples, spiked with the investigated drug, after a simple extraction procedure is described.

Adsorption↗

The use of capillary electrophoresis as part of a specificity testing strategy for mitoguazone dihydrochloride HPLC methods.

Capillary electrophoresis (CE) has been used as part of a validation experiment designed to prove the specificity of high performance liquid chromatography (HPLC) methods used for analysis of mitoguazone dihydrochloride drug substance. Data regarding accuracy, precision and sensitivity of the CE methods are presented as well as a comparison of results obtained from CE, HPLC and thin-layer chromatography (TLC) analysis of samples stressed under a variety of conditions. It was concluded that, not only were the HPLC methods being investigated specific, but that CE could potentially be used to replace HPLC for the routine assay of mitoguazone dihydrochloride.

Antineoplastic Agents↗

Bootstrap estimation of diagnostic accuracy with patient-clustered data.

RATIONALE AND OBJECTIVES: The purpose of this study was to describe a simple bootstrap approach for estimating sensitivity, specificity, and the area under the receiver operating characteristic curve for multisite test outcome data. MATERIALS AND METHODS: The performance of bootstrap estimates was evaluated and compared with that of analytic estimates by using a simulation study. Bootstrapping was demonstrated by using data from a previous study comparing two angiographic methods. RESULTS: Analytic and bootstrap estimates had similar coverage rates for 95% confidence intervals. With many sites per patient, bootstrap estimates had slightly better coverage than analytic estimates. Bootstrap percentile intervals had better coverage than asymptotic normal bootstrap intervals. CONCLUSION: Bootstrapping is a useful method of estimating confidence intervals for the area under the receiver operating characteristic curve, sensitivity, and specificity when data are correlated.

Angiography↗

The implementation of an anesthesia information management system.

BACKGROUND AND OBJECTIVE: Anaesthesia information management systems, though still not used widely, will inevitably replace handwritten records and may eventually serve as a core for the development of computerized decision support. We investigated staff expectations and the accuracy of data entry in a recently implemented commercially available anaesthesia information management system. METHODS: A structured questionnaire was administered to the staff before and 1 week and 3 months after implementation in order to assess their opinion. The quality of manual data entry, and of automatic data record was evaluated by looking for missing data and the prevalence of artefacts. RESULTS: Despite initial fears the users quickly accepted the system. Both automatic and manual data entry were found to be accurate and reliable while the prevalence of artefacts was relatively low. CONCLUSIONS: A commercially available anaesthesia information management system can be easily implemented and used instead of paper charts.

Adult↗

The influence of measured versus assumed uptake of oxygen in assessing pulmonary vascular resistance in patients with a bidirectional Glenn anastomosis.

AIMS: To determine the accuracy of data relating to pulmonary vascular resistance data in patients with a bidirectional Glenn anastomosis as calculated using predicted versus measured uptake of oxygen. METHODS: We studied retrospectively the data from 33 patients with a bidirectional Glenn anastomosis who underwent cardiac catheterisation prior to surgery to complete the Fontan circulation. Their weight ranged from 5.4 to 51.7 kg, and they were aged up to 12 years. Uptake of oxygen was measured using the Deltatrac II metabolic monitor. From the calculated indexed pulmonary vascular resistance, cases were stratified according to the risk of failure of the subsequent Fontan circulation. The six patients with a resistance of greater than 4 Um2 were deemed at high risk, the six with a resistance from 3 to 4 Um2 at moderate risk, and the 21 patients with a resistance less than 3 Um2 at low risk. Uptake of oxygen was also estimated from the predictive formulas of Lindahl, Lundell et al. and LaFarge and Miettinen. The indexed resistance was similarly calculated using these formulas and a comparable stratification of risk made from this data. RESULTS: The predicted values for uptake of oxygen were consistently higher than those measured, leading to an underestimation of indexed resistance, with mean difference between -0.62 and -1.57 Um2. This difference resulted in misclassification of between five and nine of the 12 patients considered at moderate or high risk as being at low-risk. No other haemodynamic data could reliably separate the subjects deemed at low-risk from those considered to be at high-risk. A transpulmonary gradient of greater than 7 mm of mercury was found to be 100 percent specific for elevated indexed resistance, but only 60 percent sensitive. CONCLUSIONS: In patients with bidirectional Glenn anastomoses, all formulas based on predictive uptake of oxygen lead to underestimation of the true indexed pulmonary vascular resistance, to an extent that could significantly influence clinical decision-making. The transpulmonary gradient is not a reliable surrogate for indexed pulmonary vascular resistance.

Blood Pressure↗

Oxygenation-linked subunit interactions in human hemoglobin: analysis of linkage functions for constituent energy terms.

Resolution of the linkage functions between oxygenation and subunit association-dissociation equilibria in human hemoglobin into the constituent microscopic terms has been explored by numerical simulation and least-squares analysis. The correlation properties between parameters has been studied using several choices of parameter sets in order to optimize resolution. It is found that, with currently available levels of experimental precision and ranges of variables, neither linkage function can provide sufficient resolution of all the desired energy terms. The most difficult quantities to resolve always include the dimer-tetramer association constant for unliganded hemoglobin and the oxygen binding constants to alphabeta dimers. A feasible experimental strategy for overcoming these difficulties lies in independent determination of the dimer-tetramer association constants for unliganded and fully oxygenated hemoglobin. These constants, in combination with the median lignad concentration, provide an estimate of the energy for total oxygenation of tetramers which is essentially independent of the other constituent energies. It is shown that if these separately determinable parameters are fixed, the remaining terms may be estimated to good accuracy using data which represents either linkage function. In general it is desirable to combine information from both types of experimental quantities. A previous paper (Mills, F.C., Johnson, M.L., and Ackers, G.K. (1976), Biochemestry, 15, the preceding paper in this issue) describes the experimental implementation of this strategy.

Hemoglobins↗

MXAN analysis of the XANES energy region of a mononuclear copper complex: applications to bioinorganic systems.

The near edge XAS spectra of the mononuclear copper complex [Cu(TMPA)(OH(2))](ClO(4))(2) (1) have been simulated using the multiple scattering edge simulation package MXAN (or Minuit XANes). These simulations, which employ the muffin-tin (MT) approximation, have been compared to simulations generated using the finite-difference method (FDM) to evaluate the effect of MT corrections. The sensitivity of the MXAN method was tested using structural models that included several different variations on the bond angles and bond distances for the first-shell atoms of 1. The sensitivity to small structural changes was also evaluated by comparing MXAN simulations of 1 and of structurally modified [Cu(TMPA)(L)](n)(+) complexes [where L = -O-(F(8)TPP)Fe(III), -F, -OPO(2)(O-p-nitrophenyl)Zn(II)(TMPA), and -NCMe] to the experimental data. The accuracy of the bond distances obtained from the MXAN simulations was then examined by comparison to the metrics of the crystal structures. The results show that MXAN can successfully extract geometric information from the edge structure of an XAS spectrum. The systematic application of MXAN to 1 indicates that this approach is sensitive to small structural changes in the molecule that are manifested in the XAS edge spectrum. These results represent the first step toward the application of this methodology to bioinorganic and biological systems.

Chemical Phenomena↗

Computational study of the thermochemistry of organophosphorus(III) compounds.

The enthalpies of formation of organophosphorus(III) compounds have been calculated at the G3X, G3X(MP2), and B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d,p) levels of theory using the atomization energy procedure and the method of isodesmic reactions. The Delta f H298 degree values for 50 relatively large molecules with up to 10 non-hydrogen atoms, such as P(CH3)3, P(C2H5)3, P(OCH3)3, n-C4H9OPCl2, [(CH3)2N]2PCl, (C2H5)2NPCl2, and [(CH3)2N]2PCN, have been calculated directly from the G3X atomization energies. A good agreement between the known experimental values and G3X results for 14 compounds provides support to our predictions for remaining species whose experimental enthalpies of formation are unknown or known with relatively large uncertainties. On the basis of our calculations and sometimes conflicting experimental data a set of internally consistent enthalpies of formation has been recommended for organophosphorus(III) compounds. Our computational results call into question the experimental enthalpies of formation of P(C2H5)3 and P(n-C4H9)3. From comparison with most reliable experimental data, the accuracy of the theoretical enthalpies of formation is estimated as ranging from 5 to 10 kJ/mol. The recommended Delta f H298 degree values were used to derive the group additivity values (GAVs) for 45 groups involving the phosphorus(III) atom. These GAVs significantly extend the applicability of Benson's group additivity method and may be used to estimate the enthalpies of formation of larger organophosphorus(III) compounds, where high level quantum chemical calculations are impracticable.

Computer Simulation↗

Plasma surface modification of organic materials: comparison between polyethylene films and octadecyltrichlorosilane self-assembled monolayers.

Low-pressure low-frequency NH3 plasmas have been used for the surface modification of bulk polyethylene films and of octadecyltrichlorosilane (OTS) self-assembled monolayers deposited on oxidized silicon wafers. The incorporation of nitrogen-containing groups by the plasma treatment has been followed by contact angle measurements and by X-ray photoelectron spectroscopy. The surface degradation of the OTS monolayers due to plasma etching has been measured separately by optical ellipsometry with subnanometric accuracy. Our data show clear evidence for the existence of an optimum treatment time, yielding a high density of NH2 functional groups without significant variation of the structural features of the organic material. Self-assembled monolayers appear as excellent model systems to characterize the effects of plasma discharges on polyolefins. In particular, they allow testing the influence of molecular orientation, packing density, and crystallinity on the final results.

Ammonia↗

Common conditions of the aging male: erectile dysfunction, benign prostatic hyperplasia, cardiovascular disease and depression.

With increasing life expectancy, medical profession will be faced with the task of ensuring that the large, aging population remains healthy and vital despite the face of increasing healthcare costs. Naturally, urology as a specialty is concerned with important geriatric issues. This article will focus specifically on the aging male population and the health problems that most frequently plague them. Four major, non-cancer, disease states have been identified that adversely effect males over the age of 50. These conditions are: erectile dysfunction (ED), benign prostatic hyperplasia (BPH), cardiovascular disease (CVD) and depression. A literature search of PubMed was conducted using the key words ED, BPH, CVD and depression as well as ADAM (Androgen Decline in the Aging Male) and quality of life (QoL). NIH and WHO conference proceedings and publications were also referenced to insure detail and accuracy of data. Information was then organized and correlated in order to provide a detailed description of the key conditions and their interrelatedness. The spectrum of research performed thus far regarding this topic has done little to investigate the effects, causes and correlations between these conditions. Research has been done linking two or three of these conditions; however, there remains to be information discussing the four disease states in terms of their possible cause and effect relationships or the effectiveness of parallel, multi-disciplinary approach to their therapy. This report calls attention to the benefits of viewing and researching the above mentioned conditions as possibly interrelated, as opposed to the traditional view of them as separate, unrelated and independently treatable disease states. ED, BPH, CVD and depression are all common conditions that accompany aging and negatively impact QoL. They almost always develop with age and precipitate considerable morbidity and may even result in mortality. Furthermore, the presentation of one condition may correlate with the development of another. The inter-relation of these conditions, as evident from their underlying similarities, cause-and-effects relationships and therapeutic consequences, should be enough to warrant a multidisciplinary approach to their research. This approach, combined with careful choice of therapy, parallel and singular, will help providers reach their goal to keep patients healthy, and more importantly happy, late into their life, thus realizing the concept of "successful aging".

Aged↗

Cholinergic and GABAergic modulation of medial septal area: effect on working memory.

The role of the septohippocampal pathway in working memory was investigated by direct microinfusion of compounds into the medial septal area (MSA). Behavior was measured by performance in a continuous spatial alteration task in a T maze, and hippocampal theta rhythm was also recorded. Intraseptal saline had no effect on choice accuracy or hippocampal theta rhythm. Tetracaine decreased choice accuracy and theta rhythm 10 min, but not 90 min, after infusion. Likewise, muscimol and scopolamine produced a transient, dose-dependent suppression of hippocampal theta rhythm and a simultaneous dose-dependent impairment in choice accuracy. A significant correlation (r = .78) emerged between a compound's influence on theta rhythm and its effect on choice accuracy. The data support a role for the septohippocampal projection in working memory and suggest that gamma-aminobutyric acid and acetylcholine may have opposing influences on neurons in the MSA.

Acetylcholine↗

Substeps within the 8-nm step of the ATPase cycle of single kinesin molecules.

Kinesin is a molecular motor that moves processively by regular 8-nm steps along microtubules. The processivity of this movement is explained by a hand-over-hand model in which the two heads of kinesin work in a coordinated manner. One head remains bound to the microtubule while the other steps from the alphabeta-tubulin dimer behind the attached head to the dimer in front. The overall movement is 8 nm per ATPase cycle. To investigate elementary processes within the 8-nm step, we have developed a new assay that resolves nanometre displacements of single kinesin molecules with microsecond accuracy. Our data show that the 8-nm step can be resolved into fast and slow substeps, each corresponding to a displacement of approximately 4 nm. The substeps are most probably generated by structural changes in one head of kinesin, leading to rectified forward thermal motions of the partner head. It is also possible that the kinesin steps along the 4-nm repeat of tubulin monomers.

Animals↗

A highly informative SNP linkage panel for human genetic studies.

We have developed a highly informative set of single-nucleotide polymorphism (SNP) assays designed for linkage mapping of the human genome. These assays were developed on a robust multiplexed assay system to provide a combination of very high accuracy and data completeness with high throughput for linkage studies. The linkage panel is comprised of approximately 4,700 SNPs with 0.39 average minor allele frequency and 624-kb average spacing. Based on almost 2 million genotypes, data quality was shown to be extremely high, with a 99.94% call rate, >99.99% reproducibility and 99.995% genotypes consistent with mendelian inheritance. We constructed a genetic map with an average 1.5-cM resolution using series of 28 CEPH pedigrees. The relative information content of this panel was higher than those of commonly used STR marker panels. The potent combination of this SNP linkage panel with the multiplexed assay system provides a previously unattainable level of performance for linkage studies.

Algorithms↗

Establishing a national pediatric stem cell transplantation registry in Iran addressing implementation and data quality challenges.

The Iranian Pediatric Hematopoietic Stem Cell Transplantation Registry (IPED-HSCT) was established to enhance data collection, improve patient outcomes, and support clinical research in pediatric hematopoietic stem cell transplantation. This study aimed to assess the feasibility and reliability of implementing a standardized registry in pediatric settings. A community-based participatory study was conducted across three pediatric HSCT centers in Iran. The registry development involved a multi-phase approach, including pilot testing and the implementation of a web-based system. Data were collected from fifty pediatric patients who underwent HSCT for both malignant and non-malignant conditions, with a focus on data completeness and user satisfaction. Statistical analyses were performed using IBM SPSS Statistics. The registry achieved a data completeness rate exceeding 90%, with a participant demographic of 31 males (62%) and 19 females (38%). Rigorous quality control measures and real-time validation rules were implemented, enhancing data reliability. User feedback indicated high satisfaction with the platform's design and training sessions. Challenges included variations in long-term follow-up data collection across centers. The IPED-HSCT Registry demonstrates that establishing a robust pediatric HSCT registry is feasible even in resource-limited settings. Its innovative features offer a scalable model for similar initiatives in developing countries. Future research should focus on ensuring long-term sustainability and fostering international collaborations to improve pediatric HSCT outcomes globally. not applicable.

Humans↗

Sampling for a longitudinal study of the careers of nurses qualifying from the English pre-registration Project 2000 diploma course.

This paper describes the processes involved in selecting a sample, from the eight English regional health authorities, of nurse qualifiers from all four branches of the Project 2000 pre-registration diploma course, for a longitudinal study of nurses' careers. A simple random sample was not feasible since accurate information about the population could not be obtained and the study design involved recruiting participants by personal visit. A multi-stage approach was therefore adopted in which 'college of nursing' was taken as the primary sampling unit. Sampling was further complicated by the fact that adult branch students could generally only be visited in larger groups than was ideal. Information obtained during pilot work about the accuracy of data about the population, course completion rates and the proportion of students who were likely to agree to participate was used to calculate required sampling fractions. The final sample was therefore a function of this information and the practicalities of recruiting nurses into the study.

Career Mobility↗

The national fetal death file.

The most comprehensive source of US data on fetal deaths of 20 gestational weeks or greater is available through the National Vital Statistics System (NVSS). The NVSS is a collaborative effort between the independent reporting areas (the individual States and the territories), and the federal government or its agent, the Centers for Disease Control, and Prevention's National Center for Health Statistics (NCHS). The federal government has no authority to register vital events. The registration of births, deaths, fetal deaths, marriages, and divorces is solely a state responsibility. However, NCHS is mandated by law to produce national data based on vital events. To promote the uniformity necessary to create a national file from this decentralized system, NCHS attempts to influence state systems via the development of certain standards, primarily, The Model State Vital Statistics Act and Regulations (The Model Law), and the Standard Certificates and Reports. The Model Law definitions for live birth, fetal death and induced termination of pregnancy are based on international standards set by The World Health Organization. All states have definitions of fetal death consistent with the Model Law. The Model Law also recommends reporting requirements for fetal death, but state requirements vary. This variation results in differences in reporting of fetal deaths among areas. Other limitations to the national fetal death file include: the under-reporting of fetal deaths incidence, higher than acceptable levels of missing data for some items, and the accuracy of the data reported. Also of concern is the potential misclassification of fetal deaths and short-lived live births. These limitations are amenable to improvement. The upcoming revision of the US Standard Report of Fetal Death addresses these issues and offers an opportunity to strengthen the quality of fetal death data. The development of worksheets, detailed specifications and instruction manuals, and a reformatted cause of death section should importantly enhance the quality of national fetal death file and ultimately reduce the incidence of these tragic events.

Cause of Death↗

[Cost-utility analysis of contrast-enhanced MR angiography with automated table-translation for diagnosis and therapy planning in patients with peripheral vascular disease].

PURPOSE: To analyze the cost-utility of contrast-enhanced MR angiography (ceMRA) in the diagnosis and the planning of surgical or interventional treatment in patients with peripheral arterial occlusive disease. MATERIALS AND METHODS: Additional costs and incremental costs per quality-adjusted life-year for ceMRA were calculated by a decision model. The costs of ceMRA and conventional angiography were compared. Treatment was either surgery or PTA. A retrospective analysis of 24 patients provided the data for the diagnostic accuracy of ceMRA. The data about quality of life assessment were taken from the literature. Costs were calculated in Euro using the current fee schedule. The influence of the individual parameters on the model was estimated from a sensitivity analysis. RESULTS: Per quality-adjusted life-year, ceMRA added euro; 24,408.60 in cases undergoing radiologic intervention and euro; 24,191.32 in cases treated surgically. CONCLUSION: Despite its high costs, ceMRA is an effective diagnostic procedure considering patient benefits. Additional costs do not exceed an acceptable range.

Adult↗

[Chances and risks of prevention in elderly people for the three major cancers: breast-, prostate- and colorectal cancers].

The big three, breast cancer (BC), prostate cancer (PC) and colorectal carcinoma are the most frequent malignancies world wide and also typical tumors of advanced age. Therefore the question to screen and how to screen for these tumors in the elderly is the main question for reduction of the total cancer burden and mortality in all western countries. BREAST CANCER (BC): The age related risk of BC increases from 1 : 2,500 at age 30+ to > 1 : 10 at age 80. Nevertheless, most of the national BC-Screening-Programs stop at age 60 or earlier. Therefore the majority of all advanced i. e. T (4) stages of BC are found in women age > 60. Frequently it is suggested that age related comorbidity should eliminate the benefit of treatment. Recently two longitudinal studies have clearly shown that correct standard treatment is as effective in elderly as in younger individuals. Mammography (MG) has been shown to reduce mortality of BC significantly with best results for specificity and sensitivity at age 70+. PROSTATE CANCER (PC): The screening situation of PC is quite different to BC, because risk profiles are poorly defined and the benefit of radical prostatectomy is not clearly demonstrated in the early non symptomatic stages of PC. At the other side watchful waiting leads to an elevated frequency of incontinence and enuresis as well. Two studies are now under progress and may possibly change the situation; but the final results are expected 2005-2008 at the earliest. Therefore an assisted individual decision making is the only recommendation at this time. COLORECTAL CANCER (CC): Risk groups are clearly defined. Risk of the elderly (> 60) is the average risk. The incidence increases from < 50/10 (5) to more than 500 at age 75+(male) and 500 (female). When to start and when to stop screening? Experts give the advice to begin at age 50 and to end at age 80; but this is not really evidence based. There are several unanswered questions and open problems: we are not exactly informed about complication rates of colonoscopy during the screening programs. There is a lack of data according accuracy of barium enema, virtual colonoscopy and genetic stool test in comparison to colonoscopy in combination with fecal occult blood test (FOBT). And adherence to screening is not well documented among informed patients. However, effectiveness of CC-screening (FOBT alone or in combination with colonoscopy) has been documented in three high randomised trials which have shown a disease specific mortality reduction of 15-33 % over a period of 8-13 years. But it must be clear that the economic resources must be mobilised individually or by insurance: offering the testing of only FOBT for ten years to one thousand persons can save one life.

Adult↗