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[HLA immunogenetic markers in predicting therapeutic resistance in paranoid schizophrenia].

A study was made of the incidence of HLA histocompatibility antigens of A, B and C loci in 100 male patients suffering from paranoid continuous schizophrenia associated with hallucinatory paranoid symptomatology during the formation in them of therapeutic resistance. In accordance with the clinico-pathogenetic philosophy, 2 groups of resistant patients were formed: an "endogenous" one (because of rapid progression) and a "pharmacogenous" one (secondary, formed by the mechanisms of "adaptation" to neuroleptics). In addition, a group of "nonresistant" patients (a reference one) was also distinguished. The data were compared to those obtained in normal subjects (50 men) and to those derived within the distinguished groups, employing mathematic computation of the risk coefficient. It has been shown that in contrast to the group of normal subjects, the general group of patients suffering from paranoid schizophrenia manifested the accumulation of the HLA antigens A2, A9, W7 and B15. The accumulation of the HLA antigens A2 and A11 was characteristic of the patients suffering from "endogenous" resistance, which distinguished those patients from normal subjects, from "nonresistant" patients and those with "pharmacogenous" resistance. The HLA phenotype A2,11 can be regarded as a potential marker of progression (risk grades 9.8). Besides, it has been demonstrated that the HLA antigens B7 may attest to risk of tolerance to psychopharmacotherapy and formation of "pharmacogenous" resistance (risk grades 4.3).

Adult

An instrument to monitor physiological and environmental parameters associated with heat stress on an ambulatory subject.

This paper outlines the development and construction of an instrument for use on an ambulatory subject which monitors selected physiological and environmental parameters that are a reflection of the degree of physiological strain associated with heat stress. The resulting instrument is rugged, reliable, and uses existing practical technology for in-the-field ambulatory monitoring, and provides minimal restriction to subject movement. The physiological parameters monitored (heart rate and skin temperature) were selected following examination of systemic, skin, and psychoneurotic heat disorders, with the environmental parameters (wind velocity, ambient temperature and relative humidity) based on existing heat stress indices' correlation with physiological parameters. A microprocessor is utilized for data acquisition, mathematical computation and long term storage, and software for downloading the data to a large mainframe computer is provided. Following calibration of the transduction circuits, the instrument was assembled and tested. Improvements are required to obtain the reliability originally envisaged. Additional field trials would see the collection of data to establish criteria to determine the values of the parameters monitored enabling prediction of the onset of heat stress in hot, humid environments.

Ambulatory Care

Matrix formula for intraocular lens power calculation.

The matrix calculation was applied to Gaussian optics. Matrices were defined for a single diopter, a lens, an association of two centered systems having the same axis when the origins are taken at the vertices of the first and last refracting surfaces. The matrix formula then was used to calculate the power of the emmetropizing lens implant, and its results compared with the ones obtained by five other formulas.

Biometry

[The experimental action of continuous YAG-laser radiation on the structures of the posterior eye segment].

The effects of fiber optics YAG laser continuous irradiation on the structures of the posterior segment of the eye in endovitreal exposure were under study. The values of the 1.06 microns wavelength radiation absorption by the membranes of the posterior segment of the eye were defined. On the basis of mathematical computations a relationship was revealed between standard temperature and the length of exposure in various diameters of the focussed spot and radiation power of 1 W, confirmed by animal experiments.

Animals

Shoulder subluxation in hemiplegia: a radiologic correlational study.

A tridimensional (3-D) x-ray method of evaluation of the shoulder was contrasted with six clinical and radiologic techniques used to evaluate shoulder subluxation, in 50 hemiplegic subjects. The 3-D evaluation is obtained through a mathematical computation associating two x-rays of the same shoulder, one taken at 0 degree (anteroposterior) and the other at a 45 degrees oblique view. A vector is thus obtained quantifying the separation from the apex of the humeral head to the inferior border of the glenoid fossa. The Y component (cephalocaudal) of this vector is used to represent the inferior displacement of the humeral head. The six other techniques of evaluation were: a) palpation, or the number of finger breadths inserted between the acromial process and the head of the humerus; b) anthropometry, or the distance between the acromial process and the lateral epicondyle of the humerus; c) templates, or the use of four schemas representing different degrees of separation of the humeral head from the glenoid fossa; d) a measure of the relation of the center of the humeral head to the center of the glenoid fossa; e) the vertical distance between the center of the humeral head and the center of the glenoid fossa; and f) the vertical distance between the apex of the humeral head and the inferior border of the glenoid fossa. Correlation coefficients contrasting the 3-D x-ray technique and the six other measures ranged from .738 to .995. The high level of precision and reliability of the 3-D measure indirectly validated the other measurement techniques.

Female

Interpretation of laboratory results using multidimensional scaling and principal component analysis.

Principal component analysis (PCA) and multidimensional scaling (MDS) are a set of mathematical techniques which uncover the underlying structure of data by examining the relationships between variables. Both MDS and PCA use proximity measures such as correlation coefficients or Euclidean distances to generate a spatial configuration (map) of points where distances between points reflect the relationship between individuals with their underlying set of data. Multidimensional scaling, when compared to PCA, gives more readily interpretable solutions of lower dimensionality and does not depend on the assumption of a linear relationship between variables. Both MDS and PCA were applied to electrolyte profiles of patients with acute renal failure and patients without apparent disease. The MDS was superior to PCA in separating renal patients from normal patients. The one-dimensional and two-dimensional solutions of MDS and PCA were compared.

Acute Kidney Injury

[Monitoring of cardiac output during use of bupivacaine 0.75% by ventriculography (99mTC)].

Fifteen patients undergoing orthopaedic surgery on the lower limbs were give continuous epidural anaesthesia with bupivacaine 0.75%. It was looked after changes in heart frequency, beat volume and changes in heart rhythm. Changes in cardiac output were investigated by ventriculography with 99mTC during 4 periods--10 min before and 10, 20 and 30 min after epidural blockade--the cardiac output was measured by a computer mathematically. Each patient received 2 mg/kg body weight of bupivacaine 0.75%. Besides the observation of blood pressure, heart rate and electrocardiogram the venous plasma levels of bupivacaine were measured up to 60 min after blockade. The results showed no changed in cardiac output. Except for one case with bradycardia--which could be treated with atropine--no changes in heart frequency occurred. Tachy- or bradycardia was not seen at all. Besides rare respiratory sinus arrhythmia no arrhythmia could be detected. The venous plasma levels of bupivacaine increased after 30 min up to 0.81 microgram/ml. The highest concentration measured was 1.45 microgram/ml 10 min after injection of bupivacaine. According to the results of the study the following statement can be given: Following bupivacaine 0.75% (2 mg/kg) given epidurally no changes in cardiac output, no changes in beat frequency, no pathological changes in cardiac rhythm and no specific cardiac toxicity related to bupivacaine 0.75% could be found in this study.

Adult

[Adipocyte size in primary hypertriglyceridemia with and without obesity (author's transl)].

Adipose tissue cellularity of patients with endogenous hypertriglyceridemia whether associated with obesity or not has been studied by means of a semiautomatic method of counting and sizing osmium tetroxide fixed adipocytes. Cell population distributions were analyzed by mathematical computation. The Coulter Counter system was able to determine mean diameter (or volume) and cell size dispersion which defined adipocyte population. An overall shift of cell population size has been found to characterize adipose tissue cellularity of the different groups examined. Adipocyte population in the obese was defined by increased fat cell size with overlapping distributions between both groups of same weight. Nevertheless normolipemic obese patients were characterized by larger cell size than hypertriglyceridemic subjects matched for adiposity index. The results are discussed in relation to the removal defect found in endogenous hypertriglyceridemia.

Adipose Tissue

A mathematical model and computer simulation study of insulin receptor regulation.

A homeomorphic mathematical model of cell surface insulin receptor regulation is developed. The overall structure of the model is based on molecular mechanisms suggested by in vivo and in vitro experimental evidence from many different cell types. Model parameters correspond to cellular processes which are constrained by known boundry value conditions. As an example, computer simulation results are compared with published data from BC3H-1 myocytes in culture. With appropriate parameter choice, this model is able to simulate data from other cell types. Cellular processes which are explicitly represented in the model include: bound and unbound receptor endocytosis, receptor recycling, intracellular receptor degradation, and state-dependent receptor synthesis. Most of these processes are represented as first-order events. Using more complex representations of the model structure with higher order rate constants or saturable pathways does not qualitatively improve simulation results. Simulations are able to reproduce ligand-induced down and up regulation of receptors as well as the initial spontaneous display of surface insulin receptors. To demonstrate the behavior of our model and illustrate its utility for explaining insulin receptor regulation for a variety of conditions, simulations for which experimental data is unavailable for direct comparison are also shown. We believe the structure of our model is sufficient to explain insulin receptor regulation in a wide variety of cell types. In addition our model may aid in understanding the receptor component of insulin resistance (decreased sensitivity or responsiveness to insulin) seen in pathological states such as obesity and diabetes mellitus. Finally, this model may be applicable to the study of the regulation of other polypeptide hormone receptors.

Cell Membrane

A mathematical model and computer simulation study of insulin sensitive glucose transporter regulation.

A mathematical model of insulin sensitive glucose transporter regulation is developed. Model structure is based on experimental evidence from adipocytes and myocytes. Model parameters correspond with known cellular processes. As an example, computer simulation results are compared with data from rat adipocytes. Cellular processes explicitly represented in the model include state-dependent glucose transporter synthesis and degradation rates, insulin sensitive glucose transporter translocation rates, and a glucose transporter endocytosis rate. Most of these processes are represented as first-order events. Using more complex representations of the model structure (e.g. higher order rate constants or saturable pathways) or alternative structures did not result in qualitatively better results. The model is able to accurately simulate the insulin sensitive, insulin concentration dependent, reversible translocation of glucose transporters observed in normal adipocytes. The model is also able to accurately simulate the changes in regulation of glucose transporter translocation observed with increases in cell surface area. Finally, the model can simulate pathogenic states which induce impairment of glucose transporter regulation (e.g. altered glucose transporter regulation in adipocytes from rats on high fat diets, rats with streptozotocin induced diabetes, and fasted rats). Since the structure of our model is sufficient to explain glucose transporter regulation in both normal and pathological states, it may aid in understanding the post-receptor components of insulin resistance (decreased sensitivity or responsiveness to insulin) seen in pathological states such as obesity and diabetes mellitus.

Adipose Tissue

Validation of a mathematical procedure for computer analysis of flow cytometric DNA data in human tumors.

The determination of tritiated thymidine labeling index and the percentage of cells with S phase DNA content was performed on cell suspensions obtained from 69 patients with non-Hodgkin's lymphoma. The distributions of cells in the cell cycle by computer analysis of flow cytometric data were obtained by two mathematical procedures: the widely adopted Fried model and a new one proposed by Bruni et al. A significant agreement was observed by checking the Spearman index (rs) between the percentages of cells in the different cell cycle phases (G0/1, rs = 0.76; S, rs = 0.60; and G2 + M, rs = 0.43; p less than 0.001) determined by the two procedures. Similarly, a good correlation was observed between the labeling index (LI) and the S phase values obtained by the Fried (rs = 0.45, p less than 0.001) and Bruni (rs = 0.69, p less than 0.001) models, but with a higher agreement for the latter one. The S phase by the Bruni model was also superior in predicting LI: in fact, by employing the S cutoff value of 12%, a better agreement between low LI and low S phase or high LI and high S phase was observed with the Bruni procedure (90%) than with the Fried model (72%). Finally, the analysis of the prognostic significance of the different kinetic variables confirmed the prognostic relevance of LI at any time; the S phase percentage as determined by Bruni et al. was discriminant of survival only at shorter times, and no prognostic significance could be ascribed to S phase according to the Fried procedure.

Adult