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Investigation of human right ventricular cast specimens.

Fifty human right ventricular cast specimens were subjected to X-ray cineangiography in biplane right anterior oblique and left anterior oblique (RAO/LAO) projection. From the silhouettes seen in the two projection planes we estimated areas and lengths using a light-pen minicomputer system and calculated the volumes using various methods. The calculated volume values were compared with the true values determined by water displacement. The methods were then arranged is order of decreasing accuracy. Criteria for judging model quality were the mean squared deviations, correlation coefficient, and residual variance. The most accurate calculation of the right ventricular volume was obtained with Ferlinz' method and our own empirical approach.

Cardiac Volume↗

Is there a role for psychology in ulcer disease?

The discovery of the importance of bacterial factors in the etiology of ulcer disease has led to a neglect of psychological factors. However, both earlier theoretical and empirical approaches implicating these factors are supported by more recent studies, both epidemiological and experimental. While not ignoring the unquestioned role of Helicobacter, it is important for future research to recognize the multi-factorial nature of ulcer disease by which several factors, including stress, bacteria and non-steroid antiinflammatory drugs, may interact to drive a pre-pathology (erosions or ulcerations) to a pathological state (ulcer). Calls for general eradication programs should be cautioned in the light of possible unwanted side effects.

Animals↗

Association between diarrheal duration and nutritional decline: implications for an empirically validated definition of persistent diarrhea.

In an empiric approach to develop the definition of persistent diarrhea, we evaluated the relationship between diarrheal duration and risk of ensuing clinically significant decline in nutritional status, in a cohort of 395 children < 24 mo. Weights were obtained at the onset of diarrhea (wt I) and after three months interval (wt II). The occurrence of an adverse outcome (AO) was defined as a decline of -- 5% in NCHS weight for age (% WFA) between weights I and II or death in this interval. The risk of AO was similar for episodes of / or > 7 days while it was substantially higher in episodes with > 14 days duration (45%) than for shorter duration episodes, relative risk (RR) = 2.5 (p < 0.001). Relative risk remained similar for duration thresholds of 21 (2.3) and 28 days (2.6). As episode durations greater than 14 days are associated with substantial elevation of the risk of clinically cogent sequelae, such episodes may be termed 'persistent' at least in terms of poor prognostic expectations.

Chronic Disease↗

Immunoaffinity chromatography.

The basic procedure of immunoaffinity chromatography (IAC) is described. The insoluble support matrices available for IAC and their activation chemistries, including some of the most recently introduced, are reviewed. Means of selecting the most appropriate monoclonal antibody (MAb) are described, although an empirical approach is still required for the final choice of antibody. Precise methods of running IAC columns are surveyed including the binding, washing, and elution stages, although no precise recommendations can be made particularly for the elution step since this is unique to a particular MAb and antigen. All IAC sorbents lose activity with time through a combination of MAb inactivation and ligand leakage. The relative importance of the two phenomena is discussed, and suggestions are made to minimize the problem along with an indication of the relative stabilities of a range of coupling chemistries. A sample of the proteins purified by IAC is given together with pointers to the future of the technique.

Animals↗

Which will be the most useful interferon?

Promising signs of clinical success using interferon in cancer patients have spurred the interferon boom and pharmaceutical companies, lured by a potential lucrative market, are expanding their investment in the production of this natural drug. This paper points out that the interferons known so far have different pharmacokinetic and therefore it would be important, for the future clinical trials, to correlate pharmacokinetic behaviours with therapeutic efficacy. The empirical approach in use today may lead to some failure but, on the other hand, it may help in deciding more rapidly which interferon, or combination of interferons, is more effective. Furthermore, the importance of continuing the search for an ideal interferon inducer is stressed, owing to the growing awareness that interferon is a powerful antiviral and antiproliferative agent but, probably, needs other modulators to exert its full therapeutic potential.

Escherichia coli↗

How many patients and blood levels are necessary for population pharmacokinetic analysis? A study of a one compartment model applied to cyclosporine.

OBJECTIVE: This paper describes a method to determine the number of patients and the number of blood levels which are appropriate for a pharmacokinetic population analysis. METHODS: We studied this question by performing 203 runs of population analysis, using the NPEM algorithm with a one compartment model, starting with only one patient and only one blood level, then 2 patients with one blood level each, until reaching 38 patients each with 5 blood levels. Data were obtained from liver transplant patients treated with cyclosporine. RESULTS: For 2, 3, 4 or 5 blood levels, the values of median clearance (CL) converged and became almost equal after about 10 patients were studied. The value then remained stable and the variation was fairly small. With only one blood level per patient, the variation was greater. In contrast, with one blood level, median CL became similar to groups having 2, 3, and 4 blood levels only after about 35 patients had been studied, versus about 10. Similar results were found for the median values of the volume of distribution (V). For a one compartment model with parameters of V and CL, from 15 to 20 patients with 2 blood levels may be enough to perform a reasonable population pharmacokinetic analysis; the values of the pharmacokinetic parameters were very similar to those obtained with 3 to 5 blood levels and with more patients. However, a subpopulation probably requires more patients and at least 4 or 5 blood levels per patient to be recognised. CONCLUSION: Examination of converging pharmacokinetic parameter values by stepwise increases in the number of patients and blood levels appears to be a pragmatic and empirical approach to determine the possible number of patients and blood levels required for population pharmacokinetic analysis.

Cyclosporine↗

Medicinal mushroom modulators of molecular targets as cancer therapeutics.

Empirical approaches to discover anticancer drugs and cancer treatments have made limited progress in the past several decades in finding a cure for cancer. The expanded knowledge of the molecular basis of tumorigenesis and metastasis, together with the inherently vast structural diversity of natural compounds found in mushrooms, provided unique opportunities for discovering new drugs that rationally target the abnormal molecular and biochemical signals leading to cancer. This review focuses on mushroom low-molecular-weight secondary metabolites targeting processes such as apoptosis, angiogenesis, metastasis, cell cycle regulation, and signal transduction cascades. Also discussed in this review are high-molecular-weight polysaccharides or polysaccharide-protein complexes from mushrooms that appear to enhance innate and cell-mediated immune responses, exhibit antitumor activities in animals and humans, and demonstrate the anticancer properties of selenium compounds accumulated in mushrooms.

Agaricales↗

Optimization of agitation and aeration conditions for maximum virginiamycin production.

To maximize the productivity of virginiamycin, which is a commercially important antibiotic as an animal feed additive, an empirical approach was employed in the batch culture of Streptomyces virginiae. Here, the effects of dissolved oxygen (DO) concentration and agitation speed on the maximum cell concentration at the production phase, as well as on the productivity of virginiamycin, were investigated. To maintain the DO concentration in the fermentor at a certain level, either the agitation speed or the inlet oxygen concentration of the supply gas was manipulated. It was found that increasing the agitation speed had a positive effect on the antibiotic productivity independent of the DO concentration. The optimum DO concentration, agitation speed and addition of an autoregulator, virginiae butanolide C (VB-C), were determined to maximize virginiamycin productivity. The optimal strategy was to start the cultivation at 450 rpm and to continue until the DO concentration reached 80%. After reaching 80%, the DO concentration was maintained at this level by changing the agitation speed, up to a maximum of 800 rpm. The addition of an optimal amount of the autoregulator VB-C in an experiment resulted in the maximal production of virginiamycin M (399 mg/l), which was about 1.8-fold those obtained previously.

4-Butyrolactone↗

Cross sections of electron inelastic interactions in DNA.

The cross sections of electron inelastic interaction in DNA are calculated using the dielectric response theory and Penn statistical approximation, with the exchange correction included. An empirical approach to obtain optical energy loss function is given for the organic compounds without available optical data. Comparisons of the calculated data with available experimental and theoretical results have been done to show the reliability of the approach proposed in this work. Using this approach, the total inelastic cross sections for five bases: guanine, adenine, thymine, cytosine and uracil have been calculated in the energy range of E< or =10 keV and compared with those recently obtained with the Deutsch-Mark formalism and the Binary-Encounter-Bethe model, respectively. An equivalent unit of the DNA molecule is constructed according to the contents of A-T and G-C base pairs in DNA, and is divided into five constituents, i.e. sugar-phosphate and four bases. The total inelastic cross sections for the constructed unit of the DNA molecule and its constituents have also been calculated.

Binding Sites↗

Electron stopping power and inelastic mean free path in amino acids and protein over the energy range of 20-20,000 eV.

Systematic calculations of stopping power (SPs) and inelastic mean free path (IMFP) values for 20-20,000 eV electrons in a group of 15 amino acids and a simple protein have been performed. The calculations are based on the dielectric response model and take into account the exchange effect between the incident electron and target electrons. The optical energy-loss functions for the 15 investigated amino acids and the protein are evaluated by using an empirical approach, because of the lack of experimental optical data. For all the considered materials, the calculated mean ionization potentials are in good agreement with those given by Bragg's rule, and the evaluated SP values at 20 keV converge well to the Bethe-Bloch predictions. The data shown represent the first results of SP and IMFP, for these 15 amino acids and the protein in the energy range below 20 keV, and might be useful for studies of various radiation effects in these materials. In addition, the average energy deposited by inelastic scattering of the electrons on this group of 15 amino acids, on the protein, on Formvar and on DNA, respectively, has been estimated for energies below 20 keV. The dependences of the average energy deposition on the electron energy are given. These results are important for any detailed studies of radiation-induced inactivation of proteins and the DNA.

Amino Acids↗

Nongonococcal and Nonchlamydial Cervicitis.

Cervicitis encompasses a variety of gynecologic conditions. Although inflammation on a Papanicolaou smear may be indicative of true cervical inflammation, establishing a diagnosis of mucopurulent cervicitis (MCP) is more clinically useful. MCP seems to be analogous to nongonococcal urethritis in men. Many cases of MCP are related to Chlamydia trachomatis infection, but the majority of cases have other potential causes. Other possible pathogens include Neisseria gonorrhoeae, Trichomonas vaginalis, Ureaplasma urealyticum, Mycoplasma genitalium, herpes simplex virus, and cytomegalovirus. Many cases may be related to cervical ectopy. MCP is a marker for endometritis, salpingitis, and adverse pregnancy outcomes. Given the current shortcomings in our understanding of this disease, an empiric approach to evaluation and treatment is suggested.

Journal Article↗

Apraxia.

In this review, we present a summary of some of the most pertinent new research on aspects of apraxia. Rather than attempt a review of all neurologic syndromes that have been identified as forms of apraxia, such as buccofacial, truncal, apraxia of eye opening, and apraxia of speech, we focus on current literature and trends in the study of limb apraxia. Although the classic empirical approach to the study of apraxia has been through systematic neuropsychologic assessment of various aspects of the syndrome, questions remain regarding the exact neural substrate that forms the foundation of the praxis system. More recent work using sophisticated neuroimaging methods has yielded a wealth of new data that contributes significantly to our understanding of the neuroanatomic correlates of this complex disorder. In addition, the results of recent sophisticated neuropsychologic studies have suggested modifications to classic cognitive models of apraxia. A discussion of current work and directions for future research are also provided.

Apraxias↗

Use of quantitative affinity chromatography for characterizing high-affinity interactions: binding of heparin to antithrombin III.

The versatility of quantitative affinity chromatography (QAC) for evaluating the binding of macromolecular ligands to macromolecular acceptors has been increased substantially as a result of the derivation of the equations which describe the partitioning of acceptor between matrix-bound and soluble forms in terms of total, rather than free, ligand concentrations. In addition to simplifying the performance of the binding experiments, this development makes possible the application of the technique to systems characterized by affinities higher than those previously amenable to investigation by QAC. Addition of an on-line data acquisition system to monitor the concentration of partitioning solute in the liquid phase as a function of time has permitted the adoption of an empirical approach for determining the liquid-phase concentration of acceptor in the system at partition equilibrium, a development which decreases significantly the time required to obtain a complete binding curve by QAC. The application of these new QAC developments is illustrated by the determination of binding constants for the interactions of high-affinity heparin (Mr 20,300) with antithrombin III at three temperatures. Association constants of 8.0 +/- 2.2 x 10(7), 3.4 +/- 0.3 x 10(7), and 1.0 +/- 0.2 x 10(7) M-1 were observed at 15, 25, and 35 degrees C, respectively. The standard enthalpy change of -4.2 +/- 0.6 kcal/mol that is calculated from these data is in good agreement with a reported value obtained from fluorescence quenching measurements.

Antithrombin III↗

Behavior analysis, program development, and transfer of control in the treatment of self-injury.

This case study illustrates an empirical approach to the diagnosis, treatment, and controlled follow-up of self-injurious clients. Following an assessment period, during which environmental factors associated with a severely retarded adolescent's self-injury were identified, the contingent application of protective equipment was combined with a differential reinforcement procedure (DRO) and implemented in a multiple baseline design across two hospital settings. Results showed a marked decrease in the rate of self-injury. Upon discharge from the hospital, the program was successfully replicated at the adolescent's residential center, again using a multiple baseline design across settings.

Adolescent↗

Chaotic dynamics in autonomic nervous system activity of a patient during a psychotherapy session.

Chaos theory and nonlinear dynamical modeling have been applied successfully in a variety of scientific fields ranging from the physical sciences to population biology. More recently, investigators have modeled long-term psychological processes by applying this paradigm to subjective measures. Yet, mathematically rigorous dynamical modeling of transient psychodynamic processes remains uncharted. Human behaviors and intrapsychic processes often defy prediction, yet psychodynamic theory views these as fundamentally deterministic. We postulate that a nonlinear dynamical analysis of mental states and mental control processes may help reconcile the paradox that seemingly random mental states are thought ultimately to result from deterministic, rather than stochastic, psychological processes. As an initial empirical approach, we examined spontaneously occurring autonomic activity of a patient during 1 hr of psychotherapy and illustrate that cardiac responses associated with psychologically meaningful events possess nonlinear characteristics indicative of chaos. Such nonlinear analyses may shed light on fundamental issues of psychological functioning.

Adult↗

Protein purification using combined streptavidin (or avidin)-Sepharose and thiopropyl-Sepharose affinity chromatography.

The major problem usually encountered in the application of the (strept)avidin-biotin system to the purification of proteins (or other biological molecules) lies in the difficult reversion of the interaction between immobilized (strept)avidin and the adsorbed biotinylated protein. Among the proposed solutions is the selective biotinylation of the entity to be purified by a disulphide-containing biotinylated reagent which allows its recovery from (strept)avidin gels by dithiothreitol (DTT) treatment. As emphasized by the example of angiotensin II receptor purification, achieved using this strategy, optimum reduction of this disulphide bridge may require improvement of its accessibility using denaturating agents such as sodium dodecyl sulphate or urea. However, these agents release important amounts of (strept)avidin. Two general ways of solving this problem are proposed. One solution takes advantage of the absence of cysteine in the streptavidin sequence: the protein to be purified is selectively readsorbed to thiopropyl-Sepharose through the thiol function generated on DTT cleavage of the biotinylated reagent. The other solution is an empirical approach to make possible the use of avidin, which possesses cysteine residues: combined avidin-Sepharose and thiopropyl-Sepharose chromatography proved efficient when carried out in the presence of urea as denaturing agent.

Animals↗

Polypeptide secondary structure determination by nuclear magnetic resonance observation of short proton-proton distances.

The use of proton-proton nuclear Overhauser enhancement (NOE) distance information for identification of polypeptide secondary structures in non-crystalline proteins was investigated by stereochemical studies of standard secondary structures and by statistical analyses of the secondary structures in the crystal conformations of a group of globular proteins. Both regular helix and beta-sheet secondary structures were found to contain a dense network of short 1H-1H distances. The results obtained imply that the combined information on all these distances obtained from visual inspection of the two-dimensional NOE (NOESY) spectra is sufficient for determination of the helical and beta-sheet secondary structures in small globular proteins. Furthermore, cis peptide bonds can be identified from unique, short sequential proton-proton distances. Limitations of this empirical approach are that the exact start or end of a helix may be difficult to define when the adjoining residues form a tight turn, and that unambiguous identification of tight turns can usually be obtained only in the hairpins of antiparallel beta-structures. The short distances between protons in pentapeptide segments of the different secondary structures have been tabulated to provide a generally applicable guide for the analysis of NOESY spectra of proteins.

Aprotinin↗

Hormones in breast cancer: update 1978.

The role of cytoplasmic estrogen receptor (ER) assays in determining therapeutic strategies for advanced breast cancer is certainly well established. The use of ER assays in the primary breast tumor specimen to predict for early recurrence and ultimate survival is a new finding, however, and will probably be employed in future trials of adjuvant therapy. The prevalence and significance of nuclear-bound ER still requires additional clarification. Our previous suggestion that progesterone receptor measurements might be a useful marker for hormone dependence in advanced breast cancer is gaining support and may soon have a place in routine therapeutic decision-making. The emphasis on early adjuvant therapy has hastened the search for a safe endocrine therapy that would have good patient compliance and achieve remission rates comparable to previous agents and procedures. Antiestrogens show promise of meeting these requirements. We are now beginning an era in which primary and secondary systemic therapies for breast cancer can be based on sound biologic principles. The empirical approach is outdated.

Animals↗