Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Problem Formulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources
PubMed1991

Delayed onset of cardiac arrhythmias from sustained-release verapamil.

Sustained-release products in overdose are known to produce prolonged effects as well as delayed onset. The availability of sustained-release calcium channel blockers may produce an initial misleading picture for patients who are at risk for serious toxicity. We report the cases of two adults who had delayed onset of arrhythmias after ingestion of sustained-release verapamil. In both cases, a single dose of activated charcoal was administered, but the patients still developed toxicity. Some of the unique problems encountered with sustained-release formulations are discussed, and 24-hour cardiac monitoring for sustained-release calcium channel blocker overdoses, despite a possible early asymptomatic period, is suggested.

Adult↗
PubMed2000

[The internal consistency and content validity of the Spanish version of the Asthma Autonomy Questionnaire].

The Asthma Autonomy Questionnaire (AAQ) was designed to evaluate asthmatics' desire to learn about their disease and to make decisions. The AAQ consists of 26 items distributed in two scales: Preferences in the Search for Information (PSI, 8 items) and Preferences in Decision Making (PDM, 6 general items and 12 related to 3 scenarios depicting asthma in stable phase, during mild exacerbation and during severe exacerbation). The aim of this study was to analyze the internal consistency (Cronbach's-coefficient) and content validity (factorial analysis of principal components) of the AAQ. After translation and back translation, the Spanish version of the AAQ was administered to 115 adult asthmatics of both sexes and differing levels of severity. The alpha coefficients for the two scales and 3 scenarios ranged from 0.42 (PSI) to 0.73 (stable phase scenario); only for the stable-phase scenario were values high or statistically acceptable. Factorial analysis reproduced the content of the scales only approximately, with some items proving to relate to factors that were different from the scale they originally belonged to. These results indicate that, in its current formulation, the AAQ presents important measurement problems and revision is advisable.

Adult↗
PubMed2002

Stabilization of S-adenosyl-L-methionine promoted by trehalose.

S-adenosyl-L-methionine (SAM), an important metabolic intermediate of mammals, is a well-known therapeutic agent. The molecule is chemically unstable, both in solution and in dry state, and forms different degradation products. Because the chemical instability represents a real problem during the preparation of therapeutic formulations, we investigated the capacity of some sugars to improve the SAM stability over time. In the present work, we demonstrated that the disaccharide trehalose exercises a protective effect towards the lyophilized SAM slackening its degradation (65% of SAM was detected after 50 days at 37 degrees C). A parallel study, performed to stabilize the SAM into lyophilized yeast cells enriched in the sulfonium compound, assessed the positive effect of trehalose also in whole cells, but in lesser measure.

Drug Stability↗
PubMed2000

Factors limiting the oral bioavailability of N-acetylglucosaminyl-N-acetylmuramyl dipeptide (GMDP) and enhancement of absorption in rats by delivery in a water-in-oil microemulsion.

The bioavailability (BA) of radio-labelled N-acetylglucosaminyl-N-acetylmuramyl dipeptide (GMDP) was low when administered by oral gavage as an aqueous solution to conscious male Sprague-Dawley rats (8.3+/-4.4% (mean+/-S.D., n=3)). To assess the likely factors contributing to the poor BA of GMDP, the stability of GMDP in the lumen of the gastrointestinal (GI) tract was examined in vitro, using ex vivo GI contents. GMDP was degraded by the contents of the small intestine, caecum and large intestine but was more stable in stomach contents. The permeability coefficient (p(app)) of GMDP in isolated sections of rabbit ileum was 1.67x10(-6) cm/s in the mucosal to serosal direction and was not significantly different in the serosal to mucosal direction, indicating that GMDP is poorly permeable and passively transported across the intestinal wall. First pass metabolism was considered to be unlikely to be the primary limitation to the oral bioavailability of GMDP and therefore, that the oral bioavailability of GMDP was likely limited by instability in the lumen of the gastrointestinal tract and low intestinal permeability. A water-in-oil (w/o) microemulsion formulation subsequently developed to address these problems was trialed in a preliminary bioavailability study in rats and enhanced the bioavailability of GMDP ten-fold when administered intraduodenally, indicating that w/o microemulsions may represent a viable mechanism for enhancing the bioavailability of poorly GI-stable and poorly permeable peptide-based molecules.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2001

[EGs-Ray, a program for visualization of Monte Carlo calculations in radiation physics].

A Windows program is introduced which allows a relatively easy and interactive access to Monte Carlo techniques in clinical radiation physics. Furthermore, this serves as a visualization tool of the methodology and the results of Monte Carlo simulations. The program requires only little effort to formulate and calculate a Monte Carlo problem. The Monte Carlo module of the program is based on the well-known EGS4/PRESTA code. The didactic features of the program are presented using several examples common to the routine of the clinical radiation physicist.

Computer Simulation↗
PubMed1998

'Theory of mind' skills during an acute episode of psychosis and following recovery.

BACKGROUND: A neuropsychological formulation of schizophrenia has suggested that problems with meta-representation underpin both positive and negative symptoms. This study tested Frith's account by asking patients experiencing an acute episode of psychosis to complete a set of tasks that involved Theory of Mind (ToM) skills. METHODS: Fourteen patients who fulfilled criteria for schizophrenia, 10 deluded patients who were suffering from psychotic disorders other than schizophrenia and 12 depressed patients completed second-order false belief tasks, a test which involved substitution of a co-referential term in a linguistic description of an event, and metaphor and irony tasks. The battery of tests was completed during the acute phase and following recovery. Selection of these patient groups allowed comparisons to be made between schizophrenia patients and non-schizophrenia patients and between patients with and without persecutory delusions. RESULTS: Schizophrenia patients, who had a multiplicity of positive and negative symptoms, performed significantly worse than non-schizophrenia patients on some of the ToM tasks during an acute episode. Patients with delusions of persecution and reference did not perform significantly worse than non-deluded patients on ToM tasks. There was no significant difference between groups in performance on any of the tasks at recovery. CONCLUSIONS: The results provide at best weak support for Frith's account and it remains unclear whether the ToM deficits demonstrated are genuine deficits or are a result of information-processing overload. However, it is clear that difficulties interpreting interpersonal contexts, as shown by some schizophrenia patients, are state rather than trait characteristics.

Adult↗
PubMedDate not supplied

Prediction of ligand-receptor binding thermodynamics by free energy force field (FEFF) 3D-QSAR analysis: application to a set of peptidometic renin inhibitors.

A methodology is presented and applied in which the accurate estimation of ligand-receptor binding thermodynamics is achieved by formulating the calculation as a QSAR problem. When the receptor geometry is known, the free energy force field (FEFF) ligand-receptor binding energy terms can be calculated and used as independent variables in constructing FEFF 3D-QSARs. The FEFF 3D-QSAR analysis of a series of transition state inhibitors of renin was carried out. From a statistical analysis of the free energy contributions to the binding process, FEFF 3D-QSARs were constructed that reveal the change in solvation free energy upon binding and the intramolecular vacuum internal energy of the ligand in the unbound state are the most significant FEFF terms in determining the binding free energy, delta G. Other terms, such as ligand stretching, bending, and torsion energy changes, the intermolecular van der Waals interaction energy, and change in ligand conformational entropy upon binding, are also found to make significant contributions in some FEFF 3D-QSAR delta G models and in delta H and delta S binding models. Overall, a relatively small number of the thermodynamic contributions to the ligand-receptor binding process dominates the thermodynamics of binding in a given model.

Amino Acid Sequence↗
PubMed1995

Depression research methodologies in the Journal of Personality and Social Psychology: a review and critique.

Personality and social psychological studies of depression and depressive phenomena have become more methodologically sophisticated in recent years. In response to earlier problems in this literature, investigators have formulated sound suggestions for research designs. Studies of depression published in the Journal of Personality and Social Psychology (JPSP) between 1988 and 1993 were reviewed to evaluate how well these recommendations have been followed. Forty-one articles were examined for adherence to 3 suggestions appearing consistently in the literature: (a) multiple assessment periods, (b) multiple assessment methods, and (c) appropriate comparison groups. The studies published in JPSP have not adhered well to these standards. The authors recommend resetting minimum methodological criteria for studies of depression published in the premier journal in personality and social psychology.

Anxiety Disorders↗
PubMed2002

In vitro evaluation of amino acid prodrugs of novel antitumour 2-(4-amino-3-methylphenyl)benzothiazoles.

Novel 2-(4-aminophenyl)benzothiazoles possess highly selective, potent antitumour properties in vitro and in vivo. They induce and are biotransformed by cytochrome P450 (CYP) 1A1 to putative active as well as inactive metabolites. Metabolic inactivation of the molecule has been thwarted by isosteric replacement of hydrogen with fluorine atoms at positions around the benzothiazole nucleus. The lipophilicity of these compounds presents limitations for drug formulation and bioavailability. To overcome this problem, water soluble prodrugs have been synthesised by conjugation of alanyl- and lysyl-amide hydrochloride salts to the exocyclic primary amine function of 2-(4-aminophenyl)benzothiazoles. The prodrugs retain selectivity with significant in vitro growth inhibitory potency against the same sensitive cell lines as their parent amine, but are inactive against cell lines inherently resistant to 2-(4-aminophenyl)benzothiazoles. Alanyl and lysyl prodrugs rapidly and quantitatively revert to their parent amine in sensitive and insensitive cell lines in vitro. Liberated parent compounds are sequestered and metabolised by sensitive cells only; similarly, CYP1A1 activity and protein expression are selectively induced in sensitive carcinoma cells. Amino acid prodrugs meet the criteria of aqueous solubility, chemical stability and quantitative reversion to parent molecule, and thus are suitable for in vivo preclinical evaluation.

Amines↗
PubMed2005

NK105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend in vivo antitumour activity and reduce the neurotoxicity of paclitaxel.

Paclitaxel (PTX) is one of the most effective anticancer agents. In clinical practice, however, high incidences of adverse reactions of the drug, for example, neurotoxicity, myelosuppression, and allergic reactions, have been reported. NK105, a micellar nanoparticle formulation, was developed to overcome these problems and to enhance the antitumour activity of PTX. Via the self-association process, PTX was incorporated into the inner core of the micelle system by physical entrapment through hydrophobic interactions between the drug and the well-designed block copolymers for PTX. NK105 was compared with free PTX with respect to their in vitro cytotoxicity, in vivo antitumour activity, pharmacokinetics, pharmacodynamics, and neurotoxicity. Consequently, the plasma area under the curve (AUC) values were approximately 90-fold higher for NK105 than for free PTX because the leakage of PTX from normal blood vessels was minimal and its capture by the reticuloendothelial system minimised. Thus, the tumour AUC value was 25-fold higher for NK105 than for free PTX. NK105 showed significantly potent antitumour activity on a human colorectal cancer cell line HT-29 xenograft as compared with PTX (P<0.001) because the enhanced accumulation of the drug in the tumour has occurred, probably followed by its effective and sustained release from micellar nanoparticles. Neurotoxicity was significantly weaker with NK105 than with free PTX. The neurotoxicity of PTX was attenuated by NK105, which was demonstrated by both histopathological (P<0.001) and physiological (P<0.05) methods for the first time. The present study suggests that NK105 warrants a clinical trial for patients with metastatic solid tumours.

Animals↗
PubMedDate not supplied

[Results of rehabilitation after double-sided prosthetic provision of lower limbs].

UNLABELLED: FORMULATION OF THE QUESTION: As a problem stood the question what effect the progress in orthopedic technology during the last years had on the rehabilitation results of the persons affected and how etiology and distribution of age and sex have changed. METHOD: We post-examined 50 patients during home visits who had had double-sided amputations of lower limbs and were provided from 1985 to 1993 were examined at home. RESULTS: Etiologically it concerns 25 patients with chronic arterial circulatory disturbances, 10 with trauma, 7 with congenital damages and 8 with consequences of other amputation causes. The rehabilitation results are to be evaluated with good. It could be proved that also elder double-sided amputees can be prosthetically rehabilitated if at least one knee joint could be maintained. The physiotherapeutic post-care was recognized as the weak point of rehabilitation, it has to be improved especially for the elder persons affected. CONCLUSION: The elder double-sided amputee can be enabled to a safe walk on prostheses only by optimum rehabilitation management with quick prosthetic provision and early starting intensive physiotherapeutic post-care which should go on for a much longer time than the stay in hospital.

Adult↗
PubMed2006

Many-electron self-interaction error in approximate density functionals.

One of the most important challenges in density functional theory (DFT) is the proper description of fractional charge systems relating to the self-interaction error (SIE). Traditionally, the SIE has been formulated as a one-electron problem, which has been addressed in several recent functionals. However, these recent one-electron SIE-free functionals, while greatly improving the description of thermochemistry and reaction barriers in general, still exhibit many of the difficulties associated with SIE. Thus we emphasize the need to surpass this limit and shed light on the many-electron SIE. After identifying the sufficient condition for functionals to be free from SIE, we focus on the symptoms and investigate the performance of most popular functionals. We show that these functionals suffer from many-electron SIE. Finally, we give a SIE classification of density functionals.

Journal Article↗
PubMed1988

Sexual dysfunction and the unemployed male professional.

The loss of a job by the professional male is becoming an increasingly common occurrence in modern America. A number of researchers have found that unemployment has a detrimental effect on the unemployed male professional's sex life. However, there are no specific references to this phenomena in the sex therapy research. This paper formulates an interactional conceptualization of the problem. An interactional treatment model is then proposed for helping the unemployed male professional and his wife in addressing sexual dysfunction, specifically erectile failure, associated with job loss.

Adult↗
PubMed2005

Heroin treatment demand in South Africa: trends from two large metropolitan sites (January 1997-December 2003).

Accurate prevalence data on heroin use, that points to where problems exist and the extent of these problems, is necessary to guide the formulation of effective substance abuse policy and practice. The purpose of this study was to provide surveillance information about the nature and extent of heroin use in South Africa. Data were collected from 41 specialist alcohol and other drug treatment centres in two metropolitan sites (Cape Town and Gauteng Province) between January 1997 and December 2003. Treatment indicators point to a substantial increase in heroin use over time. Most heroin users in treatment tend to be white, male, between the ages of 21 and 24 years and tend to smoke rather than inject the substance. However, this profile is changing. These emerging trends point to the possibility of heroin use becoming a serious health and social issue in South Africa and demonstrate the need for continued monitoring of heroin use patterns in the future and the development of a strategic plan for intervening before the situation deteriorates further.

Adult↗
PubMed1999

A Model of Bone Adaptation Using a Global Optimisation Criterion Based on the Trajectorial Theory of Wolff.

Julius Wolff originally proposed that trabecular bone was influenced by mechanical stresses during the formative processes of growth and repair such that trabeculae were required to intersect at right angles. In this work, we have developed an analytical parametric microstructural model, which captures this restriction. Using homogenisation theory, a global material model was obtained. An optimal structure constructed of the homogenised material could then be found by optimising a cost function accounting for both the structural stiffness and the biological cost associated with metabolic maintenance of the bone tissue. The formulation was applied to an example problem of the proximal femur. Optimal densities and orientations were obtained for single load cases. The situation of multiple loads was also considered. In this case, we observe that the alignment of principal strains with the material orthotropy direction is, in general, not possible for all load cases. Thus less restrictive microstructures (nonorthotropic) will yield higher structural stiffnesses than strictly orthotropic microstructures.

Journal Article↗
PubMed2006

A new paradigm for deriving and analyzing number needed to treat.

The inverse of the risk difference, commonly referred to as the number needed to treat (NNT) has been recently proposed as a useful measure for comparing two treatments. Since its introduction, the method has been used widely to establish comparative treatment benefits, and has also been the subject of extensive discussions among statisticians. In this paper, we examine the assumptions behind the original definition of NNT, and introduce a new formulation of the method based on a random walk model. Using stopping times, we develop a paradigm for NNT that avoids some of the conceptual and inferential difficulties and pitfalls associated with the previous work on NNT. Simulation results are provided to illustrate the bias introduced by using alternative formulations of NNT, and several open problems are suggested for future research.

Clinical Trials as Topic↗
PubMed2006

Iterative reconstruction techniques in emission computed tomography.

In emission tomography statistically based iterative methods can improve image quality relative to analytic image reconstruction through more accurate physical and statistical modelling of high-energy photon production and detection processes. Continued exponential improvements in computing power, coupled with the development of fast algorithms, have made routine use of iterative techniques practical, resulting in their increasing popularity in both clinical and research environments. Here we review recent progress in developing statistically based iterative techniques for emission computed tomography. We describe the different formulations of the emission image reconstruction problem and their properties. We then describe the numerical algorithms that are used for optimizing these functions and illustrate their behaviour using small scale simulations.

Algorithms↗
PubMed1995

Sequential bioactivation of methoxime analogs of beta-adrenergic antagonists in the eye.

Selected beta-adrenoreceptor antagonists are the antiglaucoma drugs of first choice in most cases. However, a number of significant central nervous system (CNS), cardiovascular and respiratory side-effects following topical ocular installation of beta-blockers have also been reported. Site- and stereo-specific delivery to the eye of beta-blockers was achieved by application of a sequential bioactivation of the chemical delivery system (CDS) analogs of these drugs, which are converted to the active beta-blockers only in the eye, thus systemic side effects are avoided. The corresponding ketoxime analogs of the various beta-blockers were successfully applied and one of them, Alprenoxime, was tested in humans. The main problem with these compounds, however, is formulation stability: Alprenoxime has a t90 of only 2-3 months. Thus, alternate structures were searched. Methoxime analogs of selected beta-blockers were synthesized and their chemical stability established at different pH's. Subsequently, their in vivo sequential enzymatic conversion was confirmed using HPLC. Comparative intraocular pressure (IOP) reducing activity of the methoximes were then studied using normotensive rabbits. The methoxime analogs showed significantly improved hydrolytic stability at pH approximately 7.0, the t90 is over 1 year. The in vivo sequential bioactivation, however, proceeds similarly to the oximes. The intermediate ketones and the active beta-blockers can be detected in the various eye compartments at different time intervals following topical administration of the methoximes. The mechanism of the eye-selective bioactivation and the results of the IOP reducing activity studies will be discussed.

Administration, Topical↗