How do normal subjects learn a simple adaptative task: How and why do paranoid schizophrenic patients fail?

Summary The authors studied the behavior of normal subjects and paranoid schizophrenic patients in a simple problem-solving situation. The schizophrenics were divided into two sample groups, one of individuals under treatment and the other of individuals not under treatment.The learning process involved in this problem-solving situation is very similar to an instrumental conditioning, and can be understood by means of the following assumptions: (1) the subjects use decision functions in reacting to the stimuli, although they may be not fully aware of this; (2) learning is the result of successive transformations of these decisions in the course of time; (3) the changes have specific probabilities and are related to (a) those responses which are made to the latest stimuli, and (b) a differential probability for decision functions which were effective, or only interrupted painful reinforcement, or were completely ineffective.In schizophrenics further factors of importance were (1) an inertia factor and (2) the rigidly continued use of unsuccessful or only partially successful decision criteria.The authors used a systems theory based on Galois field theory and a calculus of operators specifying three groups of subjects. A computer program based on these hypotheses was tested in a simulation experiment.The statistical evaluation of the results showed a congruence between the theoretical approach and the experimental data.This work was carried out with financial support from the Institute de Alta Cultura, Lisbon, between 1970 and 1974     

Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations

According to linear pharmacokinetics, the time course of plasma concentration of a drug, C_p,is expressed by a sum of exponential functions, C_p= _i=1 ⁿ a_i .This article describes a statistical technique to estimate the number of exponential terms, n,for the time course of drug by the application of Akaike's information criterion (AIC). Plasma concentrations of ethoxybenzamide, sulfisoxazole, bishydroxycoumarin, and diazepam measured following bolus intravenous injection were used as clinical examples for this method. Selection of models is compared between the AIC method and an Ftest method at significance levels of 5% and 1%.     

Molecular Motion of Drugs in Hydrocolloids Measured by Electron Paramagnetic Resonance

The effects of a polymer, the Li-salt copolymer of methyl-methacrylic acid, and its methyl ester on the motion of drug molecules in hydrocolloids were studied. The investigation was carried out by means of electron paramagnetic resonance (EPR) using the model nitroxide tempol, and the spin-labeled drugs lidocaine (si-lid) and dexamethasone (sl-dex). Synthesis of sl-dex was performed. Spin-labeled molecules dissolved in hydrocolloids undergo a fast reorientation motion. The decreasing order of rotational correlation times () —sl-dex > si-lid > tempol—suggests that the size and the shape of the molecules strongly affect their motion. The inhibition of motion of larger molecules depends also on their flexibility. The values indicate proportionality of the microviscosity of hydrocolloids to the polymer concentration. Rotational motion is dependent on the local environment conditioned by the free spaces between polymer molecules.     

Time-dependent RNA synthesis in different skin layers after wounding. Experimental investigations in vital and postmortem biopsies

Summary Incision wounds were made on the outer ear of rats and two biopsies were taken for examination after different survival times. In each case a biopsy was made of vital tissue and a second of postmortem tissue after refrigeration for 24 h. The biopsies were exposed to a solution containing the RNA precursor³H-cytidine for 1 h, washed and fixed in formalin. Sections 5 m thick were then autoradiographically prepared and automatically evaluated using Quantimet 920. The intravital specimens showed a significant increase in³H-cytidine incorporation in the basal cell layer after survival times of 10–24 h. No increase was seen in the stratum corneum, corium or cartilage tissue. The investigated distance from the wound margin did not have any significant bearing on the results. The³H-cytidine incorporation rate in postmortem tissue was practically identical with that of vital tissue, but no increase was observed in the rate of RNA synthesis in the basal cells as a function of the age of the wound. It may therefore be assumed that this method provides no additional information as to the age of wounds in postmortem examination.Dedicated to Professor O. Pribilla on the occasion of his 70th birthday     

Regional cycles of perfusion and non-perfusion in the lung of the term fetal rabbit.

The spatial distribution of pulmonary blood flow and its change over time was investigated in term fetal rabbits, using the plasma tracer fluorescein-isothiocyanate-labeled bovine serum albumin (FITC-BSA). A tracer bolus was injected intravenously and allowed to circulate in vivo for increasing periods of time (2-30 minutes) prior to arrest of the circulation and tissue preparation. Initially, fluorescence was present in the vasculature of 43% of lung parenchymal tissue, disposed as discrete regions or "lobules." Interspersed regions of lung tissue received no tracer inflow. With increasing tracer circulation times (10, 20, and 30 minutes), a greater percentage of lung cross-sectional area contained vessels exhibiting tracer fluorescence (64, 96, and 100%, respectively). In the fetal lung, a high pulmonary vascular resistance (PVR) is maintained. Our studies indicate that, at any given moment, fetal pulmonary blood flow is distributed only to a proportion of discrete lung "lobules," while interspersed "lobules" receive no flow at all. The "lobules" alternate between these "high" and "low" vascular resistance states with a periodicity of approximately 35 minutes, comprising 22 minutes of non-perfusion followed by 13 minutes of perfusion. This circulatory pattern permits both the maintenance of high PVR and uniform lung development. Further, by directing flow to only a portion of the vasculature, greater microvascular flow rates are achieved and hence the risk of blood sludging and stasis is reduced. Recruitment of these "non-perfused" regions at birth could thus produce a significant reduction in PVR.     

Lithium effects on time estimation and mood in manic-melancholic patients. A study of diurnal variations

Behavioural measurements of time experience and phenomenological self-ratings of mood-variations (Beecher's Mood Scale) have been carried out at night and on the following morning in a group of lithium-treated patients, in a group of psychiatric patients not given lithium, and in an untreated group of healthy subjects. In all the groups investigated the internal "clock" was slower in the morning than in the night. The results indicated that the internal "clock" in lithium-treated patients was slower than in the two other groups, but only at night. Mood variations from night ot morning were observed in all three groups. The group of lithium-treated patients had fewer complaints as to self-report of mood-variations compared with the other groups.     

Differences in muscle activity before, during, and after responding in a simple reaction time task: schizophrenics vs. normals.

Schizophrenics and normals were presented with a series of simple reaction time (RT) trials. Electromyographic techniques were used to partition RT into peripheral and central components. It was observed that contrary to the previously held assumption of "neuromuscular sameness," schizophrenics displayed a qualitatively different pattern of muscle activity in their motor responding. Differences of the observed sort could account, in part, for differences previously thought to be due solely to central dysfunction.     

Effects of scopolamine on variable intertrial interval spatial alternation and memory in the rat

A repeated measures procedure, variable intertrial interval (ITI) spatial alternation, was used to assess scopolamine effects on memory, and to compare effects of the drug on discrimination processes with effects on storage. Rats learned in two stages to press left and right levers in alternation on discrete trials separated by 5 different ITI's ranging from 2.5 to 40 s and presented in random order during the experimental session. In the first stage, alternating discrimination, alternation was controlled by a light on over the correct lever at the time of the trial; in the second stage, variable ITI spatial alternation, a centrally located panel light signalled all trials and alternation was controlled by stimuli from prior trials (memory). Alternation response occurrence declined moderately (but significantly) with increasing ITI duration in both the alternating discrimination and variable ITI spatial alternation stages; response occurrence was also significantly decreased by scopolamine treatment in both stages. Accuracy of alternating discrimination performance was not significantly altered by either ITI duration or scopolamine treatment. Accuracy of variable ITI spatial alternation performance on a trial varied inversely with the duration of the ITI that preceded the trial. Scopolamine treatment significantly reduced accuracy of lever pressing in variable ITI spatial alternation but did not alter the slope of the curves relating accuracy to ITI duration. These effects indicate that the drug impaired discrimination processes but did not alter memory storage.     

血能达片对小鼠的急性毒性和抗栓疗效

目的：测定血能达片的急性毒性和验证其抗栓疗效及选药提供依据。方法：小白鼠一次Ig血能达26g/kg；五组动物分别给血能达（XND）3g/kg,溶栓胶种（RSC）1．25g/kg，复方丹参（CDDP）1．25g/kg，消栓通络（XSTL）2．5g/kg和NS Ig,qd 1次，连续7d。第7日药后1h,IV Collagen-Adr诱发血栓[1]，观察死亡数；用毛细血管法测凝血时间，扭体法测痛。结果：小白鼠口服最大耐受量为26g/kg，临床用量的866．7倍；4种药物除消栓通络外，均有明显的抗栓作用（P＜0．05－0．01）；还证中、高剂量血能达尚有延长凝血时间和镇痛作用（P＜0．05－0．01），其余3种药则没有。结论：血能达毒性小，具有溶栓胶囊，复方丹参等效的抗栓疗效，还能抗凝和镇痛。