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PubMed2006

God's laboratory: religious rationalities and modernity in Ecuadorian in vitro fertilization.

Catholicism is the only major world religion that unequivocally bans the use of in vitro fertilization (IVF). Nevertheless, in Ecuador, Catholic IVF practitioners declare God's dominion over their IVF laboratories and clinics in explaining pregnancy outcomes. My analysis of this routine combination of spiritual and material causal models in Ecuadorian IVF contributes to two ongoing discussions about (1) the tensions between "institutional" and popular forms of Catholic religiosity and (2) the proper boundaries of science in modernity. The Catholic Church's historical and contemporary struggle to determine control of the miraculous has usually been characterized as a conflict between educated clergy and humble peasants. In the case of Ecuadorian IVF, we find, instead, educated elites and middle classes participating in this same contestation with the Church, proclaiming their direct ability to harness the power of God to effect material change on earth. This spiritual power to affect clinical outcomes does not take place just anywhere, but in clinic and lab, disrupting another set of presumptions about modern scientific practice and subjectivity. Like other Ecuadorian elites and middle classes, IVF practitioners are heirs to Enlightenment thought, and experience themselves as modern in their participation in these high-tech endeavors. But their spiritual approach to laboratory rationality does not trouble these IVF practitioners' experience of themselves as moderns, prompting a reevaluation of the narratives of scientific modernity that limit their scope to Europe and North America.

Attitude to Health↗
PubMed2006

Screening of lipid carriers and characterization of drug-polymer-lipid interactions for the rational design of polymer-lipid hybrid nanoparticles (PLN).

PURPOSE: The thermodynamics and solid state properties of components and their interactions in a formulation for polymer-lipid hybrid nanoparticles (PLN) were characterized for screening lead lipid carriers and rational design of PLN. METHODS: Verapamil HCI (VRP) was chosen as a model drug and dextran sulfate sodium (DS) as a counter-ionic polymer. Solubility parameters of VRP, VRP-DS complex, and various lipids were calculated and partition of VRP and VRP-DS in lipids was determined. Thermodynamics of VRP binding to DS was determined by isothermal titration calorimetry (ITC). The solid state properties of individual components and their interactions were characterized using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). RESULTS: Dodecanoic acid (DA) was identified as the best lipid carrier among all lipids tested based on the solubility parameters and partition coefficients. VRP-DS complexation was a thermodynamically favorable process. Maximum binding capacity of DS and the highest drug loading capacity of DA were obtained at an equal ionic molar ratio of DS to VRP. In the PLN formulation, DA remained its crystal structure but had a slightly lower melting point, while VRP-DS complex was in an amorphous form. CONCLUSIONS: Drug loading efficiency and capacity of a lipid matrix depend on the VRP-DS binding and the interactions of the complex with the lipid. A combined analysis of solubility parameters and partition coefficients is useful for screening lipid candidates for PLN preparation.

Calcium Channel Blockers↗
PubMed2001

Rational use of inotropic therapy in heart failure.

Despite their theoretic appeal, agents that increase cardiac contractility (positive inotropes) have consistently been shown to increase mortality when given chronically to patients with heart failure. The routine use of inotropes as heart failure therapy in either the acute or the chronic setting is not supported by the available data. Some appropriate uses of inotropes are as temporary treatment of diuretic-refractory acute heart failure decompensations, or as a bridge to definitive treatment such as revascularization or cardiac transplantation. Although controversial, the use of inotropes as a palliative measure in the small subset of patients with truly end-stage heart failure may be appropriate. An understanding of the appropriate goals of therapy is important for both patients and physicians if rational decisions about the use of inotropes are to be made.

Cardiotonic Agents↗
PubMed2005

Fatigue in multiple sclerosis: a rational approach to evaluation and treatment.

With the publication of the Multiple Sclerosis Council Guideline on the management of multiple sclerosis (MS) fatigue, there has been increased appreciation for the role fatigue can play in MS. Secondary fatigue is fatigue caused by other etiologies than those directly related to MS. Once these causes are ruled out, fatigue is related to MS. Secondary MS-related fatigue comes as result of the symptoms of MS that drain energy. Once secondary MS causes are ruled out, then the patient is deemed as having primary MS fatigue. Fatigue management is both nonpharmacologic and pharmacologic. Occupational therapists are the major allied health providers that address the role fatigue plays in MS patients. Over the past two decades, numerous clinical trials have been conducted on drugs for treating MS-related fatigue. Of these agents, amantadine has been studied for the longest period, and has shown efficacy in about one third of patients with MS-related fatigue on several commonly used scales. Two randomized -trials of the central nervous system stimulant pemoline have yielded unimpressive results; efficacy was seen at higher doses but coupled with an unacceptable risk of adverse events. The wake-promoting agent modafinil is the only agent to show efficacy compared with placebo on the Fatigue Severity Scale, a measure that is highly resistant to "impulse answering" and is thus viewed as one of the most difficult scales on which to show -benefit. This article reviews fatigue in MS and proposes a rational strategy for evaluation and management of this most common MS symptom.

Fatigue↗
PubMed1992

Somatic symptoms in social phobia: a treatment method based on rational emotive therapy and paradoxical interventions.

Social phobia is often accompanied by somatic symptoms such as trembling, blushing, and sweating. In cases where these symptoms are predominant and, rather than the social situation, represent the feared stimulus, their unpredictable occurrence may reduce the effectiveness of an otherwise successful treatment, such as exposure in vivo. In this study, a paradoxical treatment approach, combined with rational emotive therapy, is employed with three social phobic patients with fears of blushing, trembling, and sweating, respectively. Results indicate that a paradoxical treatment may be an effective strategy in reducing somatic symptoms in social phobia.

Adult↗
PubMed1993

Efficacy of rational emotive therapy (RET) with children: a critical re-appraisal.

Proponents of rational-emotive therapy (RET) advocate its use within the school curriculum to forestall future maladjustment through the early detection and eradication of irrational beliefs. A review of 33 unpublished dissertations and four published reports found RET effective in about 25% of comparisons with wait-list, placebo, and other treatment conditions. The major effects of RET were changes in scores on self-report measures of irrational beliefs, less on emotional distress, and little or no change in behavior; essentially the same pattern of effects previously found in a similar analysis of RET in adult populations. Little justification was found for continued use of RET in schools.

Adolescent↗
PubMed1992

Rational design and synthesis of phospholipids for the two-dimensional crystallization of DNA gyrase, a key element in chromosome organization.

Properties required of lipids for two-dimensional crystallization of proteins on lipid layers at the air/water interface are discussed in terms of molecular structure. These properties are related to essential features of the overall system such as (i) the fluidity and stability of the lipid film, (ii) the affinity of the protein to be crystallized for the lipids and (iii) the accessibility of the protein to the ligand in the lipid layer as well as (iv) technical constraints of the crystallization technique. The resulting ideas were tested through the rational design and synthesis of original phospholipid structures linked to novobiocin subsequently used in the production of two-dimensional crystals of DNA gyrase (B subunit), a prokaryotic type II DNA topoisomerase.

Crystallization↗
PubMed1996

A strategy to promote the rational use of laboratory tests. International Federation of Clinical Chemistry.

These guidelines suggest how clinical chemists may promote rational laboratory use by critically evaluating the tests they offer. This may be done by documenting the clinical uses and limitations of tests in the same way that properly written up method descriptions outline analytical procedures in a particular laboratory. This information can then be promoted on result report forms, in discussion or through investigational protocols or clinical guidelines. For these to be of value they should be the result of clinical and laboratory input reflecting the local practice and facilities. They should be clearly written, easily accessible to the users and updated whenever there is a change of methodology or clinical practice. Much can be achieved by applying common sense to common knowledge and laboratories of all sizes can prepare their own material. However, national scientific societies and other professional organisations can assist local endeavour by avoiding and disseminating educational material on test evaluation, selection and use.

Clinical Laboratory Techniques↗
PubMed1992

Children's judgments in theory choice tasks: scientific rationality in childhood.

The current research examined whether children could use certain metaconceptual criteria such as the range of explanation, non-ad hocness of explanation, empirical consistency, and logical consistency to choose between competing accounts of physical phenomena. The tasks were constructed so that the conceptual content of the explanations to be evaluated was either consistent, inconsistent, or neutral with regard to children's prior knowledge. It was found that even 7-year-olds could use metaconceptual criteria such as the range, empirical consistency, and logical consistency of theories when the theories did not violate their beliefs. However only older children (11-year-olds) showed a systematic preference for non-ad hoc theories over ad hoc ones. The findings are consistent with recent work in the philosophy of science showing that, in evaluating theoretical alternatives, scientists are influenced by their prior beliefs about the domain being considered. This research demonstrates that even young children share some of the cognitive underpinnings of scientific rationality that scientists do.

Astronomical Phenomena↗
PubMed1991

Differential activation and inhibition of lymphocyte proliferation by modulators of protein kinase C: diacylglycerols, "rationally designed" activators and inhibitors of protein kinase C.

The tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) can enhance or inhibit lymphocyte proliferation. Enhancement correlated with increased interleukin 2 (IL-2) production and activation of protein kinase C while inhibition correlated with decreased IL-2 and downregulation of protein kinase C activity (D.S. Grove and A.M. Mastro, Cancer Res. 51, 82-88). In this study, various activators and inhibitors of protein kinase C were used in order to try to separate the effects of TPA on this enzyme from its effects on IL-2 production and determine if protein kinase C activity was directly or indirectly related to IL-2 production. 1,2-Dioctanoylglycerol, 1-oleoyl-2-acetyl-glycerol, phospholipase C, and two "rationally designed" activators, 6-(N-decylamino)-4-hydroxy-methylindole and 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol, were tested. Some activators enhanced proliferation in the presence of a Ca2+ ionophore, ionomycin, but not concanavalin A. Some activators suppressed proliferation and downregulated protein kinase C. Others neither downregulated protein kinase C nor inhibited IL-2 production and proliferation. However, inhibition or downregulation of protein kinase C activity always correlated with decreased IL-2 and depressed proliferation. Thus, the evidence in this and the previous study suggests that activation of protein kinase C is directly related to IL-2 production in activated T cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Urinary tract injuries in multiply-injured patients: a rational guideline for the initial assessment.

In a retrospective study involving 866 multiply-injured patients we demonstrated urinary tract injuries in 72 patients (8.3 per cent), 17 (2 per cent) of which were serious. Haematuria was a frequent finding in multiply-injured patients. In patients with serious lesions of the urinary tract, more than 35 RBCs/HPF in the sediment or macroscopic haematuria were found. All major injuries were demonstrated by the emergency intravenous urogram. Ultrasonography demonstrated contusions of the kidney or bladder and ruptures of the kidneys, but was not reliable in diagnosing ruptures of the bladder. Of 155 patients with a pelvic fracture 13 (8 per cent) had lower urinary tract injuries. In all these patients the fracture was located in the pubic arch. If a retrograde urethrogram was performed in these patients all urethral lesions were detected. We propose a rational guideline, which guarantees diagnostic accuracy of serious injuries of the urinary tract after blunt trauma, while interfering as little as possible with the resuscitative and diagnostic procedures in severely injured patients.

Hematuria↗
PubMed1996

Assessing outcome following calcaneal fracture: a rational scoring system.

Six existing clinical scoring systems for assessing outcome after calcaneal fracture are reviewed. All were applied to a diverse group of 75 patients who had sustained this injury. Stepwise multiple regression analysis was used to identify the most relevant variables within these systems. Based on this, a simplified and rational outcome scoring system was devised. This system was then tested on a further group of 41 patients and shown to comply well with the characteristics required of an objective outcome score.

Activities of Daily Living↗
PubMed1996

Rational experimental design for bioanalytical methods validation. Illustration using an assay method for total captopril in plasma.

Generally, bioanalytical chromographic methods are validated according to a predefined programme and distinguish a pre-validation phase, a main validation phase and a follow-up validation phase. In this paper, a rational, total performance evaluation programme for chromatographic methods is presented. The design was developed in particular for the pre-validation and main validation phases. The entire experimental design can be performed within six analytical runs. The first run (pre-validation phase) is used to assess the validity of the expected concentration-response relationship (lack of fit, goodness of fit), to assess specificity of the method and to assess the stability of processed samples in the autosampler for 30 h (benchtop stability). The latter experiment is performed to justify overnight analyses. Following approval of the method after the pre-validation phase, the next five runs (main validation phase) are performed to evaluate method precision and accuracy, recovery, freezing and thawing stability and over-curve control/dilution. The design is nested, i.e., many experimental results are used for the evaluation of several performance characteristics. Analysis of variance (ANOVA) is used for the evaluation of lack of fit and goodness of fit, precision and accuracy, freezing and thawing stability and over-curve control/dilution. Regression analysis is used to evaluate benchtop stability. For over-curve control/dilution, additional to ANOVA, also a paired comparison is applied. As a consequence, the recommended design combines the performance of as few independent validation experiments as possible with modern statistical methods, resulting in optimum use of information. A demonstration of the entire validation programme is given for an HPLC method for the determination of total captopril in human plasma.

Calibration↗
PubMed1996

Chemical selectivity in micellar electrokinetic chromatography. II. Rationalization of elution patterns in different surfactant systems.

Retention behavior in micellar electrokinetic chromatography (MEKC) is investigated using linear solvation energy relationships (LSERs) for two pseudo-stationary phases, one consisting of cationic micelles of tetradecyltrimethylammonium bromide (C14TAB) and the other of an anionic triblock copolymer, poly(methyl methacrylate-ethyl acrylate-methacrylic acid) (Elvacite 2669). It was found that solutes' migration behaviors in these two MEKC systems are mainly influenced by their size (V/100) and hydrogen bonding acceptor (HBA) strength (beta). However, solutes' hydrogen bonding donor (HBD) strength (alpha) has minor effects on their migration in MEKC. The characteristics of these two systems were compared to three other previously reported anionic micellar systems of sodium dodecyl sulfate (SDS) (anionic hydrocarbon), sodium cholate (SC) (anionic bile salt) and lithium perfluorooctane sulfonate (LiPFOS) (anionic fluorocarbon). It was concluded that hydrogen bonding interactions play a major role in providing different chemical selectivity among these five MEKC systems. Both C14TAB micelles and the ionic polymer of Elvacite 2669 provide hydrogen bonding acceptor (HBA) sites for solutes, which is similar to SC micelles. In fact, C14TAB is the strongest HBA, while Elvacite 2669 has HBA strength similar to that of SC micelles. On the other hand, the fluorocarbon micelles of LiPFOS are the strongest hydrogen bond donor (HBD) micelles, followed by the weak HBD SDS micelles. In general, cavity formation has little or no effect on chemical selectivity among hydrocarbon surfactant MEKC systems (i.e., SDS, SC and C14TAB). Information obtained from the LSER analysis is used to rationalize the elution patterns in MEKC with different types of pseudo-stationary phases.

Chromatography, Liquid↗
PubMed1992

Active site of trypanothione reductase. A target for rational drug design.

The X-ray crystal structure of the enzyme trypanothione reductase, isolated from the trypanosomatid organism Crithidia fasciculata, has been solved by molecular replacement. The search model was the crystal structure of human glutathione reductase that shares approximately 40% sequence identity. The trypanosomal enzyme crystallizes in the tetragonal space group P4(1) with unit cell lengths of a = 128.9 A and c = 92.3 A. The asymmetric unit consists of a homodimer of approximate molecular mass 108 kDa. We present the structural detail of the active site as derived from the crystallographic model obtained at an intermediate stage of the analysis using diffraction data to 2.8 A resolution with an R-factor of 23.2%. This model has root-mean-square deviations from ideal geometry of 0.026 A for bond lengths and 4.7 degrees for bond angles. The trypanosomid enzyme assumes a similar biological function to glutathione reductase and, although similar in topology to human glutathione reductase, has an enlarged active site and a number of amino acid differences, steric and electrostatic, which allows it to process only the unique substrate trypanothione and not glutathione. This protein represents a prime target for chemotherapy of several debilitating tropical diseases caused by protozoan parasites belonging to the genera Trypanosoma and Leishmania. The structural differences between the parasite and host enzymes and their substrates thus provides a rational basis for the design of new drugs active against trypanosomes. In addition, our model explains the results of site-directed mutagenesis experiments, carried out on recombinant trypanothione reductase and glutathione reductases, designed by consideration of the crystal structure of human glutathione reductase.

Amino Acid Sequence↗
PubMed1986

A rational approach to the differential diagnosis of arthritic disorders.

Numerous musculoskeletal and collagen diseases can affect the cervical spine and TMJs as well as other joints in the body, resulting in pain and dysfunction. A rational approach has been presented to aid in the differential diagnosis of these disorders when they involve the TMJs. When systemic inflammatory diseases such as gout, psoriatic arthritis, and rheumatoid arthritis are suspected, the patient should be seen jointly with a rheumatologist to better manage medication and rehabilitation of the patient. Although rheumatologic diseases may appear complex, they can be differentiated and managed with minimal difficulty for the dentist. Early relief of acute pain and long-term successful management, however, will depend on the clinician's ability to understand the disease process, establish an accurate diagnosis, and apply the proper therapeutic measures.

Adolescent↗
PubMed1990

The rational design and synthesis of haptens having specific activity as full agonists or full antagonists at the benzodiazepine receptor.

The use of computer graphics hardware, in conjunction with molecular modeling software, has allowed for a structural analysis of compounds that bind to the benzodiazepine receptor (BZR) in the nM range. The definition of additional binding requirements together with steric and/or hydrophobic limitations has been directly correlated with profiles of in vivo activity, both for full agonists and full antagonists. This information has been used for the rational design of haptens that contain the antigenic determinants necessary for the production of antibodies specific for either full agonists or for full antagonists at the BZR. The synthesis of these novel compounds has been completed.

Animals↗
PubMed1985

Nonimmune hydrops fetalis--a rational attitude of management.

A rational attitude of management of the nonimmune hydrops fetalis (NIHF) is stressed in order to achieve an optimal outcome of both the mother and the newborn. Of the two cases reported, both had an underlying cardiac condition. The first was due to rapid supraventricular tachyarrhythmia and responded favorably to intrauterine medication with digoxin and the subsequent delivery of a well baby. In the second case, cesarean section was performed unnecessarily for a fetal indication, since the hydropic infant died soon after birth from a severe cardiac malformation which was not unequivocally diagnosed prior to birth.

Adult↗