[Review: Problem of the interaction between excitation and inhibition in the formulation of the teachings of Ukhtomskii concerning the principle of the dominant].
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History, 20th Century↗
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Symposium on Surface Replacement Arthroplasty of the Hip. Biomechanics: mutifactorial design choices--an essential compromise?
The main flaws to be overcome in realizing the potential success of the double-cup arthroplasty procedure are failures due to femoral cup loosening, acetabular cup loosening, and femoral-neck fractures. The clinical uncertainties include the selection of a suitable patient with adequate bone stock and the technical difficulties associated with (I) reaming the acetabulum adequately, (2) reaming down onto the neck without violating it, and (3) anchoring the components securely by interdigitation of acrylic cement. The higher frictional torques of the double-cup arthroplasty designs are not a clinical loosening issue--the resulting acetabular cement-bone shear stresses are very low. Computer models of both the femoral and acetabular components predict significant stress shielding of the cancellous bone under metal femoral shells. At the rim of the femoral cup, the stresses are increased by a factor of 3 owing to the stress concentration effect and can rise to a factor of 10 if cystic or osteoporotic changes are present. This finding if confirmed in the three-dimensional models may explain some of the femoral neck fractures. The thin polyethylene acetabular cups may also cause a stress concentration effect on the underlying cement and bone. This may explain the higher incidence of radiographic loosening around the acetabulum in double-cup arthroplasty designs compared with total hip replacements. Metal-backed sockets may reduce cancellous bone stresses and appear advantageous. There is no clinical evidence of unusual wear or wear-related problems. However, new material formulations are now either in use or being planned for the double-cup arthroplasty designs. As yet, there have been no published data on hip simulator wear for the efficacy of any of the current or proposed changes. Biologic fixation appears to be the theme for the 1980s. However, the combination of technology, design instrumentation, and patient selection will be critical in achieving success with this technically difficult procedure.
Acetabulum↗
Protein release from poly(lactic-co-glycolic acid) microspheres: protein stability problems.
The enzyme, carbonic anhydrase, has been incorporated within poly(lactic-co-glycolic acid) microspheres using a double emulsion and solvent evaporation technique. The protein stability problems during the microsphere formulation procedure and during the release period were examined in relation to the protein release kinetics over a 2 month period. Different protein release profiles could be obtained depending on the polymers used. The protein release kinetics exhibited an initial fast release followed by a slow release, resulting in an incomplete protein release although the microspheres degraded significantly. The very slow release kinetics were attributed to the protein aggregation and non-specific adsorption within the microspheres. It was found that the protein was significantly denatured and aggregated during the double emulsion formulation step. Several excipients such as albumin, poly(ethylene oxide), Pluronic F-127, and gelatin, which were loaded along with the protein within microspheres, demonstrated better protein release kinetics partly due to an increase in the protein stability. The released protein from these fast degrading microspheres, however, was severely hydrolyzed and lost its catalytic activity, caused by the accumulation of degradation products in the medium.
Carbonic Anhydrases↗
Formal representation of a conceptual data model for the patient-based medical record.
We present a general architecture for the patient-based medical record as it is being developed for the SAMS, a private social security system. The conceptual data model is described in a convenient formal notation, the entity-relationship diagram. Although following the original formulation of the problem-oriented medical record (POMR), the data model was designed with a level of generalization that, functionally, makes structural differences between conventional and POMR no longer apparent. The main features of this model are its adaptability to individual work practices and its problem-oriented structure, including the representation of problems' evolution. This structure will enable physicians to organize the data, mostly collected elsewhere, by explicitly relating the facts that constitute a particular patient record, which is a simple way to store context information and clinical knowledge that is not part of patient data.
Database Management Systems↗
[Zinc and diabetes mellitus].
In patients with type 1 and 2 diabetes was frequently found: low blood zinc levels, high zincuria, severe and ubiquitous cellular depletion of zinc, increased basal and after loading blood mineral clearance, and hyperglycaemia due to the reduction of pancreatic insulin secretion and to the reduced biological action of the hormone on liver, as a consequence of chronic zinc deficit. Strong endocellular zinc depletion in diabetics; low insulin secretion; insulin biological action decrease for zinc deficit; IG-I concentration decrease, that happens in this condition; insulin and IGF-I resistance; insulin and IGF-I receptors depletion in diabetics: are strong arguments for zinc pharmacological supplementation, in gastric protective formulation, to avoid gastroenteric problems.
Diabetes Mellitus, Type 1↗
Facility location: a review of context-free and EMS models.
EMS location models are those formulated to address specific problems of emergency medical services systems; context-free location models are those developed without reference to particular applications. The literature on these two types of public facility location models is reviewed, and the development of the maximal covering model from several earlier context-free models is described, with emphasis on problem statements and articulation of service objectives. An application of the maximal covering model to fire truck location points up the ability of this model to handle multiple objectives; its ability to compare alternative solutions gives it great utility for planning and evaluating EMS systems of a wide range of complexity. Potential applications of the maximal covering model are discussed regarding EMS problems involving multiple time standards and service objectives, location of special equipment, and siting of fixed facilities.
Delivery of Health Care↗
[Ophthalmic preservatives and preparations: reality and perspectives].
Preservatives are used in order to prevent contamination of ophthalmic solutions. Besides their lack of antimicrobial efficacy in certain conditions, they raise number of problems in terms of formulation, stability, interaction with containers. There is also an increasing concern about their deleterious effects in prolonged use on ocular tissues and tear film. Various alternatives have been developed and are analysed in this article.
Anti-Infective Agents↗
Optimisation in radiotherapy. II: Programmed and inversion optimisation algorithms.
This is the second article in a three part examination of optimisation in radiotherapy. The previous article established the bases of optimisation in radiotherapy, and the formulation of the optimisation problem. This paper outlines several algorithms that have been used in radiotherapy, for searching for the best irradiation strategy within the full set of possible strategies. Two principle classes of algorithm are considered--those associated with mathematical programming which employ specific search techniques, linear programming-type searches or artificial intelligence--and those which seek to perform a numerical inversion of the optimisation problem, finishing with deterministic iterative inversion.
Algorithms↗
[Topical preparations for burns and their evaluation].
The study focused on some problems connected with the formulation of the topical preparation of the hydrocream type, intended for the treatment of dermal burns. Seven cream bases containing Emulgator E 2155, Polysorbate 80 and silicone oils were evaluated. The employed drugs included carbizocaine, lidocaine, chlorohexidine, and the immunomodulating substance glucan. A measurement of the surface tension of chlorohexidine and carbizocaine did not reveal interaction between these two drugs. Liberation tests confirmed a higher release of lidocaine in comparison with carbizocaine and chlorohexidine. The silicone oil present did not influence the release of carbizocaine, but it promoted the release of lidocaine and chlorohexidine. The determination of rheological parameters revealed that an addition of drugs influenced the flow properties of creams. The suitability of cream ointments was evaluated on the basis of their drying.
Administration, Topical↗
Processing of critical information by physicians and medical students.
In the study reported here, differences between physicians and medical students in their recall of information from clinical problems were investigated. The focus of the study was on the recognition and recall of critical cues within cases as a function of problem difficulty and the organization of clinical information. Two clinical cases in two structural forms (typical and random) were designed, and the participants' written recall of the cases was analyzed using the techniques of discourse analysis. The results show that the physicians recalled significantly more critical cues than the medical students. However, when the case had a temporally ordered, underlying disease process, the random structure of the text disrupted both the physicians' ability to recall critical cues and the accuracy of their diagnoses. The medical students were unaffected by problem type or structural form in the amount of information they recalled. The results show that the physicians and medical students formulate the information from clinical problems differently, and this difference is due to the fact that the physicians recognize patterns of familiar problems with respect to critical cues but the students do not.
Clinical Competence↗
A growth mixture theory for cartilage with application to growth-related experiments on cartilage explants.
In this paper, we present a growth mixture model for cartilage. The main features of this model are illustrated in a simple equilibrium boundary-value problem that is chosen to illustrate how a mechanical theory of cartilage growth may be applied to growth-related experiments on cartilage explants. The cartilage growth mixture model describes the independent growth of the proteoglycan and collagen constituents due to volumetric mass deposition, which leads to the remodeling of the composition and the mechanical properties of the solid matrix. The model developed here also describes how the material constants of the collagen constituent depend on a scalar parameter that may change over time (e.g., crosslink density); this leads to a remodeling of the structural and mechanical properties of the collagen constituent. The equilibrium boundary-value problem that describes the changes observed in cartilage explants harvested at different stages of a growth or a degenerative process is formulated. This boundary-value problem is solved using existing experimental data for developing bovine cartilage explants harvested at three developmental stages. The solution of the boundary-value problem in conjunction with existing experimental data suggest the types of experimental studies that need to be conducted in the future to determine model parameters and to further refine the model.
Aging↗
Gain-Loss Framing and Choice: Separating Outcome Formulations from Descriptor Formulations.
This article reexamines the assumptions underlying the disease problem used by Tversky and Kahneman (1981) to illustrate gain-loss formulation effects. It is argued that their reported effect may have been due to asymmetries in the ambiguity of the sure and risky prospects and to the entanglement of two distinct types of formulation manipulations: one having to do with the expected outcomes that are made explicit (positive vs negative) and the other having to do with the descriptors used to convey the relevant expected outcomes (lives saved/not saved vs lives lost/not lost). Two experiments using a formally equivalent problem in which these confounds were eliminated revealed no significant predictive effect of either descriptor or outcomes frames on choice, although a marginally significant framing effect was obtained in Experiment 1 when the signs of the two framing manipulations were congruent. Implications for prospect theory are discussed. Copyright 2001 Academic Press.
Journal Article↗
Data reconciliation and parameter estimation in flux-balance analysis.
Flux blance analysis (FBA) has been shown to be a very effective tool to interpret and predict the metabolism of various microorganisms when the set of available measurements is not sufficient to determine the fluxes within the cell. In this methodology, an underdetermined stoichiometric model is solved using a linear programming (LP) approach. The predictions of FBA models can be improved if noisy measurements are checked for consistency, and these in turn are used to estimate model parameters. In this work, a formal methodology for data reconciliation and parameter estimation with underdetermined stoichiometric models is developed and assessed. The procedure is formulated as a nonlinear optimization problem, where the LP is transformed into a set of nonlinear constraints. However, some of these constraints violate standard regularity conditions, making the direct numerical solution very difficult. Hence, a barrier formulation is used to represent these constraints, and an iterative procedure is defined that allows solving the problem to the desired degree of convergence. This methodology is assessed using a stoichiometric yeast model. The procedure is used for data reconciliation where more reliable estimations of noisy measurements are computed. On the other hand, assuming unknown biomass composition, the procedure is applied for simultaneous data reconciliation and biomass composition estimation. In both cases it is verified that the f measurements required to get unbiased and reliable estimations is reduced if the LP approach is included as additional constraints in the optimization.
Acetates↗
Optimization of HDR brachytherapy dose distributions using linear programming with penalty costs.
Prostate cancer is increasingly treated with high-dose-rate (HDR) brachytherapy, a type of radiotherapy in which a radioactive source is guided through catheters temporarily implanted in the prostate. Clinicians must set dwell times for the source inside the catheters so the resulting dose distribution minimizes deviation from dose prescriptions that conform to patient-specific anatomy. The primary contribution of this paper is to take the well-established dwell times optimization problem defined by Inverse Planning by Simulated Annealing (IPSA) developed at UCSF and exactly formulate it as a linear programming (LP) problem. Because LP problems can be solved exactly and deterministically, this formulation provides strong performance guarantees: one can rapidly find the dwell times solution that globally minimizes IPSA's objective function for any patient case and clinical criteria parameters. For a sample of 20 prostates with volume ranging from 23 to 103 cc, the new LP method optimized dwell times in less than 15 s per case on a standard PC. The dwell times solutions currently being obtained clinically using simulated annealing (SA), a probabilistic method, were quantitatively compared to the mathematically optimal solutions obtained using the LP method. The LP method resulted in significantly improved objective function values compared to SA (P = 1.54 x 10(-7)), but none of the dosimetric indices indicated a statistically significant difference (P < 0.01). The results indicate that solutions generated by the current version of IPSA are clinically equivalent to the mathematically optimal solutions.
Algorithms↗
Antioxidant-accelerated oxidative degradation: a case study of transition metal ion catalyzed oxidation in formulation.
Oxidation presents a constant challenge for formulation scientists trying to develop stable dosage forms. Antioxidants are commonly used in formulation to alleviate the oxidation problem but they do not always achieve the desired results. In this study, a case of antioxidant-accelerated oxidation degradation in formulation is reported. The oxidation mechanism of a development drug candidate (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (1) in solution was investigated under various oxidative conditions, which include at different oxygen level, with transition metal ion spiking, and under light exposure with presence of photosensitizer. Oxidative degradation products and kinetics were monitored by high-performance liquid chromatography (HPLC). Kinetic solvent isotope effects of I oxidation in formulation, under metal ion catalysis, and upon photocatalysis were obtained. Metal ion spiking, exposure to stainless steel, as well as introduction of antioxidants such as ascorbic acid, thioglycerol, and sodium bisulfate, accelerated the oxidative degradation. Treatment of the solution with metal chelating resin inhibited oxidation. Kinetic solvent isotope effects are in agreement with a metal-catalyzed oxidation mechanism and inconsistent with a singlet oxygen pathway. On the basis of kinetic data, an oxidative fragmentation mechanism initiated by a metal ion catalyzed active oxygen species is suggested as the primary pathway for the oxidative degradation of I. Other oxidative species may be implied in the long-term oxidative degradation. Because many antioxidants act as pro-oxidants in metal-catalyzed oxidation, controlling metal ion contamination level in the excipients and limiting available molecular oxygen are recommended for formulation development.
Antioxidants↗
[Problems and pitfalls in controlled clinical studies (author's transl)].
The problems encountered in prospective clinical trials are discussed: knowledge of the literature, precise formulation of the question answering the problem, number and qualifications of patients, duration of the trial, parameters to be measured. A surgical trial can hamper the education of the residents, or it can be devaluated by incompetent surgeons. Patients do not come for follow-up for several reasons (change of domicile, absence of disturbances, disagreeable tests).
Evaluation Studies as Topic↗
Information needs and problem solving behavior of parents of infants.
Two approaches were used to investigate the problems or issues that parents of infants encounter: the study of circumstances that are naturally recognized by the parent as an issue, and the study of simulated problems concerning commonly occurring infant care issues. A paradigm of problem solving behavior was used to formulate the component of a descriptive study for the purpose of examining the problem solving behavior of mothers during their infants' first 3 months. Mothers who participated in both studies were married or living with a partner, were 17 years or older, and had healthy infants. The objective of the first study was to capture in the mothers' own terms their specification and description of the issues on which they were working and the nature of the infant care task, including the types of help mothers used and the stressors and supports they experienced. Logs were used by 62 mothers (38 primiparae and 24 multiparae) for 90 days after their infants' births to record these issues, types of help, stressors, and supports. Predetermined categories were used to code the data. The type of help used varied significantly by category of issue. Books were used most frequently for issues of growth and development and baby care, and they were used more often than all types of clinicians combined for these types of issues. For over one-third of issues, no help of any type was used. Multiparae and primiparae did not differ significantly in the total number of issues reported, nor in the frequency with which help was used. The objective of the second study was to examine the types of goals and decision making rules that mothers applied to two simulated infant care problems: one concerning the amount of the feeding, and the second concerning noncontingent crying. Four simulated problem exercises were presented to 22 mothers (14 primiparae and 8 multiparae), using a telephone interview in the infants' first 3 months. The results of the study revealed that mothers gave a variety of names to the same problem. The types of goals that mothers identified varied by type of problem. More mothers cited competence as a goal for the crying than the feeding problem. More mothers were able to state the decision rule they had used for naming the problem than for choice of action to solve the problem (implementing).(ABSTRACT TRUNCATED AT 400 WORDS)
Adaptation, Psychological↗
Nitrate delivery systems in perspective. A decade of progress.
In recent years the use of nitroglycerin and long-acting nitrate compounds in clinical practice has been increasing. Only 10 to 15 years ago these drugs, at least in oral formulation, were felt to have no clinical utility because of concern that potent hepatic enzyme activity would degrade sufficient amounts of the nitrate compounds from reaching the systemic circulation. However, it is now recognized that oral nitrate administration when given in sufficient amounts achieves therapeutic plasma concentrations and desired clinical effects. Nitrates are routinely used for the treatment of stable and unstable angina and also play a role in therapy for complications of myocardial infarction. Nitrates are very effective agents for preload reduction in vasodilator therapy of congestive heart failure. A wide variety of nitrate delivery systems, including the standard oral and sublingual formulations, and as well as the new transdermal nitroglycerin discs and buccal nitroglycerin, are now available. Sublingual nitroglycerin, isosorbide dinitrate, and buccal nitroglycerin are used for acute treatment of attacks of ischemic chest pain. For ambulatory patients, long-acting therapy can be administered by oral, topical ointment, transdermal disc, and buccal nitroglycerin formulations. Each compound has a slightly different onset and duration of action, which is in part dose-dependent. The relative merits and problems with each of the formulations are reviewed. Intravenous nitroglycerin is now commercially available and plays an increasing role in the intensive care units. It is an ideal drug for acute chest pain syndromes, including acute myocardial infarction. Specialized tubing does not need to be employed. The wide variety of nitrate delivery systems available to physicians makes use of this tried and true therapy practical and easy to carry out for clinicians.
Administration, Intranasal↗