The nonlinear, complex sequential organization of behavior in schizophrenic patients: neurocognitive strategies and clinical correlations.

BACKGROUND: Thought disorder is a hallmark of schizophrenia and can be inferred from disorganized behavior. Measures of the sequential organization of behavior are important because they reflect the cognitive processes of the selection and sequencing of behavioral elements, which generate observable and analyzable behavioral patterns. In this context, sequences of choices generated by schizophrenic patients in a two-choice guessing task fluctuate significantly, which reflects an "oscillating dysregulation" between highly predictable and highly unpredictable subsequences within a single test session. In this study, we aimed to clarify the significance of dysregulation by seeing whether demographic, clinical, neuropsychological, and psychological measures predict the degree of dysregulation observed on this two-choice task. METHODS: Thirty schizophrenic patients repeatedly performed a LEFT or RIGHT key press that was followed by a stimulus, which occurred randomly on the left or right side of the computer screen. Thus, the stimulus location had nothing to do with the key press behavior. The range of key press sequence predictabilities as measured by the dynamical entropy was used to quantify the dysregulation of response sequences and reflects the range of fixity and randomness of the responses. A factor analysis was performed and step-wise multiple regression analyses were used to relate the factor scores to demographic, clinical, symptomatic, Wisconsin Card Sorting Test (WCST), and Rorschach variables. RESULTS: The LEFT/RIGHT key press sequences were determined by three factors: 1) the degree of win-stay/lose-shift strategy; 2) the degree of contextual influence on the current choice; and 3) the degree of dysregulation on the choice task. Demographic and clinical variables did not predict any of the three response patterns on the choice task. In contrast, the WCST and Rorschach test predicted performance on various factors of choice task response patterns. CONCLUSIONS: Schizophrenic patients employ several rules, i.e., "win-stay/lose-shift" and "decide according to the previous choice," that fluctuate significantly when generating sequences on this task, confirming that a basic behavioral dysregulation occurs in a single schizophrenic subject across a single test session. The organization or the "temporal architecture" of the behavioral sequences is not related to symptoms per se, but is related to deficits in executive functioning, problem solving, and perceptual organizational abilities.     

Riluzole does not have an acute effect on motor thresholds and the intracortical excitability in amyotrophic lateral sclerosis

Intracortical excitability in amyotrophic lateral sclerosis (ALS) is impaired. The effectiveness of the glutamate antagonist riluzole (Rilutek, Rh?ne-Poulenc Rorer) in ALS has been shown in clinical studies. In healthy subjects it modifies intracortical excitability in a frequently used double-stimulus paradigm of transcranial magnetic stimulation (TMS). Under riluzole intracortical inhibition is enhanced in healthy individuals, although not always significantly, whereas intracortical facilitation has been described as reduced [10, 11]. We wanted to find out whether riluzole affects and potentially rebalances impaired intracortical excitability in ALS. We, therefore, enrolled 13 patients with clinically and electromyographically confirmed ALS into this study. Five patients had to be excluded because motor thresholds were too high to get reliable motor evoked potentials (MEPs). In the remaining 8 patients, mean age was 59.9 +/- 11.9 years (+/- standard deviation) and mean symptom duration 9.6 +/- 2.5 months. Intracortical excitability was assessed before and 1.5 hours after the first intake of a loading dose of 100 mg of riluzole using a conventional paired-pulse TMS paradigm with interstimulus intervals (ISI) ranging from 1-30 ms and intensities adjusted to yield MEPs of 1.0 mV for test pulses and of 90% active motor threshold for conditioning pulses. Patients' baseline results were compared to those of 9 age-matched, healthy control subjects. Before drug intake, motor thresholds did not differ between groups, but there was significantly less intracortical inhibition in the ALS patient group. Riluzole intake did not significantly alter motor thresholds or intracortical excitability in the ALS patients. We conclude that riluzole does not immediately influence intracortical excitability in ALS. Our results are in contrast to the findings of Stefan et al (1998) [14] where a partial normalization of intracortical inhibition in ALS was observed after at least 5 days of drug intake. The difference between that study and our result may indicate a delayed onset of riluzole's influence on intracortical excitability.     

Intracellular ATP depletion inhibits swelling-induced -[H]aspartate release from primary astrocyte cultures

Volume expansion-sensing outward rectifier (VSOR) anion channel, also referred to as volume-sensitive organic osmolyte-anion channel (VSOAC), appears to be responsible for cell swelling-induced amino acid release in a variety of cells. One prominent feature of the VSOR/VSOAC is that non-hydrolyzed intracellular ATP binding to the channel or an accessory protein is required for its activation. In this study, the effect of intracellular ATP depletion on the swelling-induced release of -[³H]aspartate from rat primary astrocyte cultures due to exposure to either high K⁺ or hypotonic media was studied. When the cells were pretreated for 10 min with a combination of the metabolic inhibitors 2-deoxyglucose and rotenone, 100 mM K⁺ media- or hypotonic media-induced -[³H]aspartate release was completely suppressed. Added separately, each inhibitor showed only partial or no inhibition of -[³H]aspartate release, which correlated with its relative effectiveness in decreasing intracellular ATP levels. These data are consistent with the view that during high [K⁺]_o or hypotonic media-induced swelling of primary astrocyte cultures an ATP-dependent swelling-activated VSOAC channel is responsible for -[³H]aspartate release and close to normal ATP is required for full channel activation.     

Understanding the feasibility of integrated care: a rival viewpoint on the influence of actions and the institutional context

There is in Europe growing awareness that the delivery of integrated care is required to meet the demands of an increasing number of patients with multiple problems. It is also clear that the provision of integrated care is difficult to achieve. As yet, the debate about the circumstances enabling or hindering provision is not settled. The objective of this article is to generate more knowledge on this issue. It is often assumed that the feasibility of integrated care provision is caused by characteristics of the legislation, the financing system and other aspects of the institutional context. Here it is argued that these characteristics are relevant but not decisive. Based on empirical evidence from the Dutch case a rival viewpoint is presented, suggesting that it is the commitment of the actors involved, their support, and the way developments are being managed, that make the difference. Following presentation of the evidence, the implications of the findings for integrated care policy are discussed.     

Barriers to follow‐up of abnormal screening mammograms among low‐income minority women

Objective. To describe factors related to compliance diagnostic follow‐up among minority women of low socioeconomic status with abnormal screening mammograms.

Methods. A retrospective cross‐sectional survey using a structured telephone interview. Three cancer screening clinics at an urban inner‐city public hospital. All women with abnormal screening mammograms between September 1990 and January 1992 were eligible; women were interviewed in August 1992. Abnormal mammograms were those requiring specific, non‐routine clinical follow‐up; non‐compliance was defined as delayed follow‐up (four to six months after the date of the mammogram), or no follow‐up at the time of interview (more than 6 months after abnormal).

Results. Sixty‐two of 442 screened women had abnormal results; the overall rate of non‐compliance with follow‐up was 50%. Among the 42 (68%) women who agreed to be interviewed, non‐compliers were less likely to state that they had been told to receive follow‐up than compilers (65% versus 100%; p = 0.008). Non‐compliant women were less likely to have suspicious mammography interpretations (p = 0.05), and more likely to report barriers to follow‐up, such as cost of lost wages and medical care, system barriers, or fears, than compliant women (61.9% versus 9%, p = 0.01). There were no differences between the two groups for age, education, insurance, source of care, family history, knowledge or attitudes.

Conclusions. These preliminary results suggest that follow‐up of low income, minority women with abnormal screening mammograms could be enhanced by improved communication of results. Future studies should extend these findings with larger samples and in other settings and populations.     

Biliary secretion of sulindac and metabolites in man

The biliary secretion of sulindac and metabolites after a single 400 mg oral dose of the drug was studied in 3 elective gallbladder surgical patients following placement of an occludable T-tube in the common bile duct. Bile and systemic plasma were sampled at frequent intervals for up to 36 h postdose. The apparent biliary clearance (V?_cl,bilc) of the prodrug sulindac is about 25 times greater than that of the pharmacologically active sulfide metabolite. The total biliary flux of drug in normal man with an uninterrupted enterohepatic cycle, calculated from V?_cl,bile and historic mean plasma drug AUC values, averages 144 and 12·2 per cent of the dose as sulindac and the sulfide metabolite, respectively. Thus, enterohepatic recycling of the drug in man is principally in the form of the prodrug which not only limits exposure of the intestine to the active moiety but also sustains systemic concentrations of active drug upon reabsorption of the prodrug.     

Flexible fiberoptic sigmoidoscopy—The monroe clinic experience

Analysis of 5000 consecutive flexible fiberoptic sigmoidoscopies form the basis of this report. It is concluded that this method of examination of the distal large bowel is not only safe and comfortable for the patient but is a more appropriate examination than the rigid proctosigmoidoscopy because of the significant increase in pathologic material found. This examination has proven practical and acceptable in a multispecialty clinic setting and has completely replaced rigid proctosigmoidoscopy. Flexible sigmoidoscopy is now the standard "routine" examination of the rectum and distal colon. The rationale for this conclusion is presented in this timely report.