Absorption of the anxiolytic pazinaclone in animals as a criterion for species selection for toxicity studies

In rats, mice, hamsters, and guinea pigs given a 5 mg/kg oral dose of pazinaclone (CAS 103255-66-9), unchanged drug concentration in plasma was highest in mice (AUC; 90 ng.h/ml), followed in decreasing order by guinea pigs (AUC; 41 ng.h/ml), hamsters (AUC; 18 ng.h/ml), and rats (AUC; 17 ng.h/ml). In terms of plasma drug concentrations and toxicological background data, there was no better alternative rodents than mice and rats for the toxicity studies. Among rabbits, dogs, and monkeys, the dogs had the highest plasma drug concentrations: AUCs of pazinaclone in dogs and monkeys were 1035 and 458 ng. h/ml, respectively (drug concentration in rabbit plasma was very low). Of the two polymorphs, forms 1 and 2 with particle size of < or = 5 microns, the oral absorption of form 2 in rats was more efficient than that of form 1 at 1000 mg/kg: AUCs of pazinaclone after dosing of form 1 and 2 were 489 and 965 ng.h/ml, respectively. However, form 1 was selected for the toxicity studies because of the poor physico-chemical properties of forms 2. Form 3 was not included in this study, because this form was relatively unstable and contained relatively large amount of impurities. The absorption of pazinaclone in dogs was improved by decreasing its particle size: AUCs of pazinaclone after dosing of the drug having particle size of 5.5, 20.8, and 79.3 microns were 1361, 822, and 297 ng.h/ml, respectively. Since large-scale preparation of bulk pazinaclone with a particle size of 5 microns or smaller was not feasible, the drug having a particle size of about 20 microns was used in the toxicity studies. The absorption of pazinaclone was more extensive when the drug was given to fed animals as suspension. Thus, the toxicity studies were performed using form I of pazinaclone with a particle size of about 20 microns primarily in rats, mice, and dogs.     

Validation of a specific selection criterion for dental periapical radiography

We report three children with hemidystonia in whom anti-cardiolipin (aCL) antibodies were demonstrated. Systemic lupus erythematosus was excluded on the basis of both clinical and serological criteria, and the diagnosis of primary antiphospholipid syndrome (PAPS) was made. In two cases, aCL antibodies could be causally related to a presumed immune-mediated thrombotic event involving the basal ganglia as shown by magnetic resonance imaging (MRI). In the remaining patient the finding of white matter alteration on NMR might be due to cross-reactivity of anti-phospholipid (aPL) antibodies with cerebral phospholipids, resulting in demyelination. We suggest that PAPS must always be considered when isolated or recurrent focal cerebral ischaemia, and particularly hemidystonia, occur in childhood.     

p53 as a target for anti-cancer immunotherapy

The key to specific and non-toxic cancer therapy is likely to be identification and targeting of processes that are absolutely unique to the tumor. One such approach is to target cells expressing mutations in the oncoproteins that led to the development of the cancer, such as p53. In animal model systems, highly mutant p53-specific cytotoxic T cells can be induced, but it remains to be seen whether this can be translated into clinical practice, and what proportion of tumors will respond. In this review, the potential and problems of immunological targeting of mutant p53 in solid tumors are discussed.     

Replicability as a publication criterion.

From time to time various suggestions have been made on how to reduce publication lag. It has been pointed out that raising the methodological standards by which articles are judged would help solve the lag problem and, at the same time, increase the quality of published articles. One particular methodological criterion which might help the present publication lag to disappear is that of replicability--requiring every author to satisfy the editor that his major results have been repeated before the article is considered for publication. Articles using replication designs which are not satisfactory to the editor could be given lowest publication priority. Articles with no attempt at replication would be rejected. There is good reason to anticipate that use of the repeatability criterion might do more than simply increase rejections and reduce publication lag. It seems likely that, under such a built-in reward system, more studies would be designed with replication in mind, the quality of replication (and generalization) designs would improve, and a great deal of overelaborate statistical analysis will disappear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protein design as a challenge for peptide chemists

All efforts to turn the ultimate goal in protein de novo design into reality-the construction of new macromolecules with predetermined three-dimensional structure and well-defined functionality-failed because the mechanism of folding has still to be unravelled. In the present review, various attempts to apply synthetic tools for inducing native-like structural features in peptides in order to bypass the folding problem are described. Besides well-established methods for the nucleation and stabilization of secondary structures, e.g. alpha-helices, beta-sheets and beta-turns, topological templates as 'built-in' folding devices have more recently become the key elements for the induction of protein-like folding units (template-assembled synthetic proteins, TASP). Progress in the synthetic strategy and structural characterization of this new type of macromolecules opens the way for the design of functional TASP molecules.     

Patient collaboration as a criterion for the therapeutic alliance.

In this article we show that a focus on patient collaboration, as a marker for the therapeutic alliance, is advantageous not only for theory and research but also for clinical practice. This point of view in no way minimizes the importance of the therapist's activity or the clinical significance of the interaction between patient and therapist. Rather, it focuses attention on how the therapist's personality, skill, and technique interact with the problems the patient brings to psychotherapy. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Alcoholism as chronic disease: a challenge for the physician

Alcoholism is associated with a high relapse rate; within four years of a successful intensive hospital withdrawal program a good 50 percent of the patients have relapsed again. In view of this result of research into alcoholism an "aims hierarchy" has been established which meets the requirements of relapsed alcoholics while expressly rejecting the limitation of therapeutic measures to the purely somatic. Psychotherapeutic considerations that take account of the specific situation of the chronic, often multimorbid patient are applied already in the early phase of treatment. For example, relapse must not be interpreted as a failure of previous treatments or even be used as an excuse to abandon therapy.     

Edge-to-edge plane matching as a criterion for interphase boundaries of low energy

As demonstrated by Aaronson and his colleagues over five decades or so, the structure, energy, and dynamic response of interphase boundaries in metallic systems are strongly correlated. It has also become clear that very few, if any, solid/solid transformation interfaces can be considered truly “incoherent.” Most treatments of the geometry of irrational interfaces (facet planes) have focused on the density of coincidence sites or near-coincidence sites (NCS); this naturally involves consideration of the matching of densely packed atomic planes lying parallel to the facet. Edge-to-edge plane matching represents an alternative and, perhaps, more general approach to the geometry of transformation interfaces. For diffusional transformations, growth ledges are required to displace and reproduce the structure of the facet plane; their geometrical properties are distinct from those of the interfacial facets. The role of local thermodynamic driving force in determining the migration mode is assessed. Several recent observations of the transient faceting of irrational interfaces, for which the density of NCS is relatively low, have stimulated considerations of the significance of the invariant-line condition and of edge-to-edge plane matching as criteria for local minima in interfacial free energy. This article is based on a presentation made in the “Hume-Rothery Symposium on Structure and Diffusional Growth Mechanisms of Irrational Interphase Boundaries,” which occurred during the TMS Winter meeting, March 15–17, 2004, in Charlotte, NC, under the auspices of the TMS Alloy Phases Committee and the co-sponsorship of the TMS-ASM Phase Transformations Committee.     

Edge-to-edge plane matching as a criterion for interphase boundaries of low energy

As demonstrated by Aaronson and his colleagues over five decades or so, the structure, energy, and dynamic response of interphase boundaries in metallic systems are strongly correlated. It has also become clear that very few, if any, solid/solid transformation interfaces can be considered truly “incoherent.” Most treatments of the geometry of irrational interfaces (facet planes) have focused on the density of coincidence sites or near-coincidence sites (NCS); this naturally involves consideration of the matching of densely packed atomic planes lying parallel to the facet. Edge-to-edge plane matching represents an alternative and, perhaps, more general approach to the geometry of transformation interfaces. For diffusional transformations, growth ledges are required to displace and reproduce the structure of the facet plane; their geometrical properties are distinct from those of the interfacial facets. The role of local thermodynamic driving force in determining the migration mode is assessed. Several recent observations of the transient faceting of irrational interfaces, for which the density of NCS is relatively low, have stimulated considerations of the significance of the invariant-line condition and of edge-to-edge plane matching as criteria for local minima in interfacial free energy. This article is based on a presentation made in the “Hume-Rothery Symposium on Structure and Diffusional Growth Mechanisms of Irrational Interphase Boundaries,” which occurred during the TMS Winter meeting, March 15–17, 2004, in Charlotte, NC, under the auspices of the TMS Alloy Phases Committee and the co-sponsorship of the TMS-ASM Phase Transformations Committee.     

Edge-to-edge plane matching as a criterion for interphase boundaries of low energy

As demonstrated by Aaronson and his colleagues over five decades or so, the structure, energy, and dynamic response of interphase boundaries in metallic systems are strongly correlated. It has also become clear that very few, if any, solid/solid transformation interfaces can be considered truly “incoherent.” Most treatments of the geometry of irrational interfaces (facet planes) have focused on the density of coincidence sites or near-coincidence sites (NCS); this naturally involves consideration of the matching of densely packed atomic planes lying parallel to the facet. Edge-to-edge plane matching represents an alternative and, perhaps, more general approach to the geometry of transformation interfaces. For diffusional transformations, growth ledges are required to displace and reproduce the structure of the facet plane; their geometrical properties are distinct from those of the interfacial facets. The role of local thermodynamic driving force in determining the migration mode is assessed. Several recent observations of the transient faceting of irrational interfaces, for which the density of NCS is relatively low, have stimulated considerations of the significance of the invariant-line condition and of edge-to-edge plane matching as criteria for local minima in interfacial free energy. This article is based on a presentation made in the “Hume-Rothery Symposium on Structure and Diffusional Growth Mechanisms of Irrational Interphase Boundaries,” which occurred during the TMS Winter meeting, March 15–17, 2004, in Charlotte, NC, under the auspices of the TMS Alloy Phases Committee and the co-sponsorship of the TMS-ASM Phase Transformations Committee.     

Apoptosis as a criterion for sensitivity of uterine cervical adenocarcinoma to cisplatin

Two patients with uterine cervical adenocarcinoma received two courses of intra-arterial cisplatin administration. In the specimens of cervix 24 or 48 h after chemotherapy, marked apoptosis were observed. These bulky cervical tumors almost disappeared, and good PRs were confirmed by CT before operation. Apoptosis which is observed in the tissues of cervical adenocarcinoma 24 or 48 h after intra-arterial infusion of cisplatin, might be a new criterion of this chemotherapy effect.     

Akinetic mutism as a classification criterion for the diagnosis of Creutzfeldt-Jakob disease

OBJECTIVES: Among the classification criteria for the diagnosis of Creutzfeldt-Jakob disease, akinetic mutism is described as a symptom which helps to establish the diagnosis as possible or probable. Akinetic mutism has been anatomically divided into two forms--the mesencephalic form and the frontal form. The aim of this study was to delimit the symptom of akinetic mutism in patients with Creutzfeldt-Jakob disease from the complex of symptoms of an apallic syndrome and to assign it to the individual forms. METHODS: Between April and December 1996, 25 akinetic and mute patients with Creutzfeldt-Jakob disease were consecutively examined. The patients were classified according to the definition of akinetic mutism by Cairns and secondly in accordance with the features constituting the complete picture of an appalic syndrome (defined by Gerstenbrand). RESULTS: From 25 patients with definite Creutzfeldt-Jakob disease, 24 patients showed impoverishment of speech and, after a mean duration of four (range 1.1-11.2) months, almost complete absence of voluntary movements and speech. Seven patients were classified as being mute and akinetic and assigned to the mesencephalic form whereas 13 patients were classified as apallic. One patient was mute without being akinetic and four patients were comatose. CONCLUSION: Diffuse brain damage underlies akinetic mutism in patients with Creutzfeldt-Jakob disease. The term can be used as a classification criterion for the diagnosis of Creutzfeldt-Jakob disease; however, it should be applied very carefully and delimited clearly from the apallic syndrome.     

Right axis deviation as a criterion for echocardiographic evaluation of aircrew candidates

BACKGROUND: Significant pressures exist in the resource-limited environment of military aviation to select only those candidates for flight training who are both physically able to withstand the demands of the flight environment and likely to complete a career in aviation. As medical technology has advanced, uncertainty has arisen regarding the appropriate use of additional studies in the screening of aircrew candidates. At the Naval Operational Medicine Institute (NOMI), where all U.S. Navy aviation duty candidates' medical qualifications are reviewed, current policy is to perform 2D-echocardiography on all candidates who exhibit a right axis deviation of +95 degrees or greater on their initial electrocardiogram. METHODS: The records of all aircrew candidates referred to the Department of Internal Medicine for evaluation of right axis deviation during the years 1993, 1994, and 1995 were reviewed. A cost benefit analysis was performed to assess the cost effectiveness of using echocardiography to screen candidates suspected of having disqualifying physical defects based on a finding of right axis deviation on electrocardiogram. RESULTS: Of the 69 cases reviewed, only 1 candidate was disqualified due to cardiovascular disease. He suffered from a large atrial septal defect initially discovered on physical examination. CONCLUSIONS: It is not cost effective to use 2D-echocardiography to screen aircrew candidates for disqualifying cardiac defects based on a finding of a right axis deviation of +95 degrees or greater on electrocardiogram.     

MCMI-III as a treatment outcome measure for psychiatric inpatients

The Million Clinical Multiaxial Inventory-III (MCMI-III) recently was introduced to replace and update the MCMI-II. A sample of 97 psychiatric inpatients were administered the MCMI-III shortly following admission, and again 7-10 days later. Changes in the personality and symptom scales generally paralleled those found in previous work with the MCMI-II, although the mean retest interval was considerably shorter than in the earlier study. However, some differences between the two instruments were observed, confirming the need for ongoing cross-validation work on the MCMI-III as an instrument that is distinct from the MCMI-II.     

T-cell receptor peptides as immunotherapy for autoimmune disease

The observations in both mouse and rat models of experimental allergic encephalomyelitis (EAE) demonstrating restricted T-cell receptor (TCR) usage among pathogenic T cells has led to the generation of a new class of therapeutic vaccines composed of TCR V region peptides. Whether a similar approach will be of use in the treatment of human autoimmune disorders is still unclear. The experiments performed in our laboratory over the past several years have focused on two aspects of TCR peptide immunoregulation, namely, (1) how to identify the critical T-cell populations involved in the pathology of autoimmune disease, and (2) how to identify biologically relevant TCR peptides--those endogenous TCR peptides presented in association with MHC molecules on the surface of pathogenic T cells that are recognized by immunoregulatory T-cell populations. Results of our recently completed clinical studies regarding TCR V beta expression among CD4+ T cells in the cerebral spinal fluid (CSF) of patients with multiple sclerosis suggests that these cells may be an appropriate T-cell population to be targeted for TCR peptide therapy. In addition, our studies on the immune response to autologous, soluble TCR heterodimers may provide a strategy for the identification of new TCR peptide candidate vaccines.     

Salary growth as a criterion of career progress.

As a possible improvement on absolute salary as a criterion, the authors computed the annual percentage growth of the salaries of 143 engineering graduates employed in industry. Although 1st-year salaries increased markedly from 1950 to 1955, and 1957 salaries varied with years of service, the growth rates were homogeneous. The rates for different professional groups were different 1st-year salary and salary growth were unrelated. Growth was related to academic grades, but absolute salary unexpectedly had a stronger relationship. Salary growth has some useful properties, but it is not uniformly applicable. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Procedural justice as a criterion in allocation decisions.

336 undergraduates considered allocations made within 16 representative types of interpersonal relationships that varied with regard to social-emotional or task basis, cooperative or competitive style of interaction, causal or rule-directed behavior, and power distribution. Ss also rated the importance of 8 allocation criteria, such as objectivity and practicality, and of 6 criteria for judging procedural fairness, such as consistency and correctability. Results suggest that procedural justice was a more important criterion in decisions concerning resource allocations than were a variety of nonfairness criteria and that it was equal in importance to distributive justice. The meaning of procedural justice in allocations and the relation of procedural justice concerns to social allocation goals are explored. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The check list as a criterion of proficiency.

Four typical tasks were administered to a sample of 15 naval aviation structural mechanics, whose performances in process were rated on specially-constructed check lists by one or more examiners. The end-products were then independently ranked in over-all quality from best to worst by five experts. The median correlation (rho) between pairs of expert rankings was .89 and .95 for two of the tasks, and .29 and .37 for the other two. Three of the four median correlations between rankings of the end products were not significantly different from the correlations of the expert rankings with rankings of the scores obtained from the check lists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Affection for patients as a factor in therapists' outcome judgements

This study was concerned with psychotherapists' evaluations of the outcome of therapy. Staff and resident psychiatrists employed in 23-item questionnaire to rate the seccess of psychotherapy with 85 of their inpatients. These were patients for whom psychotherapy constituted a significant part of the treatment that they received in the hospital. The therapists' responses to the questionnaire items were intercorrelated. The results indicated that a major aspect of a psychotherapist's judgment of the success of treatment-as these judgments usually are employed in current psychotherapy research-is the therapist's affective reaction to the patient, Better-liked patients were viewed as having improved more. However, when the therapists' responses were subjected to factor analysis, independent Improvement and Affection factors emerged. It is suggested that when therapists' ratings of success are used in psychotherapy research they should be treated or refined statistically to minimize potential confounding with their affection for patients.     

Heat shock protein--peptide complexes as immunotherapy for human cancer

Not all medical practices are equipped to provide diabetes self-management training. Physicians can incorporate a team approach in their practice by establishing collaborative relationships with recognized diabetes education programs. The ADA's education recognition program has identified diabetes education programs that meet the National Standards for Diabetes Self-Management Education Programs. This list is available on the ADA's web site at http://www.diabetes.org/recognition and is printed twice a year in Diabetes Forecast. The National Certification Board for Diabetes Educators (NDEA) can provide a list of CDEs in your area. The South Carolina Model Diabetes Patient Education Program of DSC and SCDCP/DHEC is an excellent critical step towards obtaining ADA recognition.