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A new recognisable syndrome in three sibs with congenital heart disease, round face with depressed nasal bridge, short stature, and developmental retardation.

We report three sibs with congenital heart disease, round face with depressed nasal bridge, small mouth, short stature, developmental retardation, relatively dark skin, and high axial triradius. The chromosomes of the three patients were normal and the parents were unrelated, healthy, and of normal intelligence. The mother denied infections, drinking, drug intake, or exposure to known teratogenic agents during each pregnancy.

Abnormalities, Multiple↗

Counter-attack on cocaine trafficking: the strategy of drug law enforcement.

In the past cocaine was abused by the affluent and the famous members of society while at present it is widely abused by people in all social strata. Both abuse and availability of cocaine are increasing in the United States of America. Cocaine traffickers possess enormous assets, financial resources and means of transport that enable them to remain in operation. The incidence of violent activities, including homicides, is higher among cocaine traffickers than among traffickers in other drugs. Certain cocaine-related criminal groups are routinely engaged in wanton violence. Cocaine trafficking is closely connected with various sorts of crime, corruption and subversive activities. Suppression of cocaine traffic is among the most important priorities of the Drug Enforcement Administration (DEA). Coca plant eradication is regarded as the most effective weapon against cocaine trafficking. DEA special agents, in co-operation with their counterparts from concerned countries, are conducting intelligence exchange, international cocaine investigations and training programmes in cocaine source areas. The United States Government has focused on coordination of efforts of various concerned agencies at the federal, state and local levels to combat drug abuse and trafficking. The Department of Justice has mandated the establishment of law enforcement coordinating councils throughout the United States to ensure appropriate utilization of prosecution resources and to co-ordinate criminal investigative efforts. Task forces against organized crime are established in 12 key areas of the country. Control of precursors and essential chemicals that are used clandestine drug manufacturing is one among other measures currently being undertaken by the Government to suppress trafficking in cocaine and other drugs.

Cocaine↗

Environmental factors associated with a spectrum of neurodevelopmental deficits.

A number of environmental agents have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. Critical windows of vulnerability to the effects of these agents occur both pre- and postnatally. The nervous system is relatively unique in that different parts are responsible for different functional domains, and these develop at different times (e.g., motor control, sensory, intelligence and attention). In addition, the many cell types in the brain have different windows of vulnerability with varying sensitivities to environmental agents. This review focuses on two environmental agents, lead and methylmercury, to illustrate the neurobehavioral and cognitive effects that can result from early life exposures. Special attention is paid to distinguishing between the effects detected following episodes of poisoning and those detected following lower dose exposures. Perinatal and childhood exposure to high doses of lead results in encephalopathy and convulsions. Lower-dose lead exposures have been associated with impairment in intellectual function and attention. At high levels of prenatal exposure, methylmercury produces mental retardation, cerebral palsy and visual and auditory deficits in children of exposed mothers. At lower levels of methylmercury exposure, the effects in children have been more subtle. Other environmental neurotoxicants that have been shown to produce developmental neurotoxicity include polychlorinated biphenyls (PCBs), dioxins, pesticides, ionizing radiation, environmental tobacco smoke, and maternal use of alcohol, tobacco, marijuana and cocaine. Exposure to environmental agents with neurotoxic effects can result in a spectrum of adverse outcomes from severe mental retardation and disability to more subtle changes in function depending on the timing and dose of the chemical agent.

Adolescent↗

Neurocognitive subtypes of chronic schizophrenia.

Performance on four key neurocognitive tasks was used to search for subtypes in 104 DSM-IIIR schizophrenic patients. The tasks were the Wisconsin Card Sorting Test to index executive prefrontal cerebral function, intrusion errors from the California Verbal Learning Test to tap hippocampal-diencephalic mnestic function, bilateral hand performance on the Purdue Pegboard to index fine motor-basal ganglial function, and a pro-rated IQ from the Wechsler Adult Intelligence Scale-Revised to measure general cognitive-cerebral function. Neurocognitive data were analyzed using hierarchical and disjoint clustering procedures with Euclidean distance. A five cluster solution was considered optimal. Cluster 1 (n = 24) comprised patients with selective executive-prefrontal dysfunction; cluster 2 (n = 16) suggested normative function; cluster 3 (n = 20) involved patients with executive-motor/cortico-basal ganglial deficit; cluster 4 (n = 25) suggested dementia/multi-focal disturbance; and cluster 5 (n = 19) consisted of patients with selective motor-basal ganglial deficit. The subtypes differed significantly in age, duration of illness, and extent of hospitalization. Suggestive trends in sex composition and anti-Parkinsonian medication patterns were noted. Neurocognitive tasks combined with cluster analysis have promise in reducing and clarifying the heterogeneity of schizophrenia.

Adult↗

Molecular modelling of the androgen receptor axis: rational basis for androgen receptor intervention in androgen-independent prostate cancer.

Androgen depletion in combination with antiandrogenic agents is initially highly effective for treating prostate cancer, and is the recommended treatment for more advanced or higher-grade tumours. However, many tumours eventually become insensitive to androgens, even though the androgen receptor (AR) continues to be expressed. Computational chemistry combined with structural analysis of nuclear receptors and determination of binding affinities of natural and designed coregulators (coactivators and corepressors) provides the theoretical framework for the rational design of novel therapeutic agents directed at the AR. Adding alternative groups to various sites throughout the receptor can alter the conformation of the molecule and its functional binding with coactivators or corepressors. Possible molecules can be identified thoroughly and systematically using intelligent high-throughput screening and FASTrack chemistry (three-dimensional crystallography). Applying these techniques should eventually result in therapeutic agents for androgen-independent prostate cancer that can block binding of AR coactivators while simultaneously increasing binding of AR corepressors.

Androgen Antagonists↗

A clinical study on intellectual impairment in parkinsonian patients during long-term treatment.

The severity of intellectual impairment of 89 patients with Parkinson's disease was evaluated with the Osaka Intelligence Scale for the Aged (OISA). Based on their intelligence levels, the patients were divided into three groups: normal, slight dementia and dementia. EEGs, psychiatric complications such as hallucination, degree of motor disability, history of medication, relationship between changes in intelligence and total amount of administered drugs were also examined. There was no significant correlation between the length of duration of the illness and the degree of intellectual impairment. Two characteristic subgroups were found among our subjects: a group of patients who rapidly became demented after the onset of Parkinsonism, and a group of patients whose intelligence was preserved for a longer period. The mean age of the onset of the disease in the former group was older than that of the latter. Patients of the former group exhibited psychiatric complications and EEG abnormalities more frequently. The severity of motor disability and medications administered at the time of the OISA examination did not differ between the two groups. Deterioration of the intelligence of the patients with Parkinson's disease did not correlate with the total amount of the administered antiparkinsonian drugs.

Adult↗

Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update.

The angiotensin converting enzyme (ACE) inhibitors are a group of effective drugs with a unique mechanism of action. These drugs have proven to be useful for hypertension and congestive heart failure. Early clinical trials of captopril used doses that are now known to be inappropriately high, and dose-related adverse effects were observed frequently. The recognition that lower doses are effective has reduced the incidence of adverse reactions and resulted in improved patient tolerance. When patients are properly selected and correctable risk factors are removed, serious side effects are uncommon. Unfortunately, the early reputation of nephrotoxicity persists, as does the belief that significant blood dyscrasias, endocrine effects and rash are serious risks for the average patient. After wide use of captopril, enalapril and lisinopril, and investigational trials of nearly a dozen newer agents, a sufficiency of clinical observation, experimental evidence and accurate postmarketing recording of events is accumulating to allow insight into the major toxicities with regard to more intelligent patient selection, more rational dosing and proper identification of risk factors. The most common adverse reactions are cough and skin rash. It appears that the agents are generally not cross-reactive with regard to skin rash, although it is not clear whether this effect is drug-specific or class-specific with regard to cough. Statistically but not clinically significant lowering of haemoglobin and hematocrit is common; these effects are inconsequential in most patients. Neutropenia, once thought to be prevalent, now appears to be so only in patients with autoimmune or collagen-vascular disease; the majority of patients outside these groups are at low risk. Hyperkalaemia is a frequent occurrence. This should not be surprising in view of the effect of the ACE inhibitors on plasma aldosterone. When dietary potassium intake is regulated and sources of altered potassium excretion are identified, hyperkalaemia is seldom a serious problem. Identification of sodium and water deficits allows correction before the drugs are started, and the frequency of hypotension and hyperkalaemia caused by the drugs is quite low if these factors are properly managed. An unexpected finding emerging in recent years is the dry cough associated with ACE inhibitor therapy. Its mechanism is not definitely known. Nonsteroidal anti-inflammatory drugs may control this symptom in some patients. The frequent observation of proteinuria in patients taking ACE inhibitors has gained notice and sometimes caused undue alarm. It is difficult to separate disease effects in diabetes and hypertension from true drug effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Isotropic-sequence-order learning in a closed-loop behavioural system.

The simplest form of sensor-motor control is obtained with a reflex. In this case the reflex can be interpreted as part of a closed-loop control paradigm which measures a sensor input and generates a motor reaction as soon as the sensor signal deviates from its desired (resting) state. This is a typical case of feedback control. However, reflex reactions are tardy, because they occur always only after a (for example, unpleasant) reflex-eliciting sensor event. This defines an objective problem for an organism which can only be avoided if the corresponding motor reaction is generated earlier. The goal of this study is to design a closed-loop control situation where temporal-sequence learning supersedes a tardy reflex reaction with a proactive anticipatory action. We achieve this by employing a second, earlier-occurring and causally coupled sensor event. An appropriate motor reaction to this early event prevents triggering of the original, primary reflex. Such causally coupled sensor events are common for animals, for example when smell predicts taste or when heat radiation precedes pain. We show that trying to achieve anticipatory control is a fundamentally different goal from trying to model a classical conditioning paradigm, which is an open-loop condition. To this end, we use a novel learning rule for temporal-sequence learning called isotropic-sequence-order (ISO) learning, which performs a confounded correlation between the primary sensor signal associated to the reflex and a predictive, earlier-occurring sensor input: this way the system learns the relation between the primary reflex and the earlier sensor input in order to create an earlier-occurring motor reaction. As a consequence of learning, the primary reflex will not be triggered any more, thereby permanently remaining in its desired resting state. In a robot application, we demonstrate that ISO learning can successfully solve the classical obstacle-avoidance task by learning to correlate a built-in reflex behaviour (retraction after touching) with earlier arising signals from range finders (before touching). Finally, we show that avoidance and attraction tasks can be combined in the same agent.

Adaptation, Physiological↗

Chaotic neurodynamics for autonomous agents.

Mesoscopic level neurodynamics study the collective dynamical behavior of neural populations. Such models are becoming increasingly important in understanding large-scale brain processes. Brains exhibit aperiodic oscillations with a much more rich dynamical behavior than fixed-point and limit-cycle approximation allow. Here we present a discretized model inspired by Freeman's K-set mesoscopic level population model. We show that this version is capable of replicating the important principles of aperiodic/chaotic neurodynamics while being fast enough for use in real-time autonomous agent applications. This simplification of the K model provides many advantages not only in terms of efficiency but in simplicity and its ability to be analyzed in terms of its dynamical properties. We study the discrete version using a multilayer, highly recurrent model of the neural architecture of perceptual brain areas. We use this architecture to develop example action selection mechanisms in an autonomous agent.

Action Potentials↗

The use of antibiotics in biliary tract disease.

Antibotics are often used in the treatment of patients with biliary tract disease. Certain drugs are relatively contraindicated if there is preexisting liver dysfunction. Not all antibiotis achieve a high level in bile, and knowledge of their individual excretion rate is important for intelligent use.

Ampicillin↗

The long-term effects of cranial irradiation on the central nervous system.

Cranial irradiation and chemotherapy may have significant long-term deleterious effects on children with brain tumors. Intellectual deterioration, endocrinopathies, leukoencephalopathy, extraneural metastases, and oncogenesis may all complicate the treatment of central nervous system neoplasia. These long-term effects of therapy have important implications, as some are amenable to treatment and others may be prevented by the careful monitoring of drug and radiation administration. Until recently, the survivals of children with brain tumors were limited, so that concerns over long-term effects of therapy were unnecessary. As children with certain types of brain tumors now have a better prognosis, these long-term and possibly remediable effects have important implications. This article emphasizes radiation effects on intellect, endocrine function, and oncogenesis. Recommendations for baseline and longitudinal evaluations of children with brain tumors are suggested.

Achievement↗

Influence of stimulants on electrodermal studies in Fragile X syndrome.

Attention Deficit Hyperactivity Disorder (ADHD) is seen in the majority of children with Fragile X Syndrome (FraX). Previous work has documented an enhanced sweat response to stimuli in children with FraX compared to controls utilizing electrodermal response (EDR) measures. The present study assesses the EDRs both on and off stimulants in 19 children with ADHD and FraX compared to 17 age- and IQ-matched control patients with ADHD and developmental delays. Although the baseline EDRs were comparable between FraX patients and controls, the patients with FraX had a significant decrease in EDR amplitude and number of peaks when treated with stimulants compared to controls. This suggests that patients with FraX are more responsive to the enhancement of inhibitory systems that occur with stimulant use for ADHD. The use of a quantifiable measure, such as EDR, is recommended in future studies of treatment efficacy.

Adolescent↗

Premorbid IQ and schizophrenia. Increasing cognitive reduction by episodes.

In order to test the hypothesis that acute schizophrenia episodes have a negative impact on cognitive function, 35 consecutive non-abuse schizophrenia outpatients (age < 60) were enrolled in this study. All subjects for whom grades from the 9(th) year of the Swedish school system were available, had to complete a comprehensive computerized neuropsychological test session. Symptoms were rated by PANSS and GAF, previous episodes were tallied, and medication was logged. A premorbid cognitive score was calculated on the basis of school grades and validated by comparison with academic career and current cognitive performance (r = 0.56). Half had college level studies or higher, and the overall school grades for the group were above average. PANSS (sum = 59) and GAF [59] ratings as well as medication (M = 230 CPZ units) suggested a moderate symptom level. Two patients had no neuroleptic drugs, 16 had atypical and 17 had conventional neuroleptics. Vocabulary was intact. On average, patients had lost 1 standard deviation (SD) in most cognitive tests but response time slowing amounted to 3.5 SD. There were no differences in cognition between drug types and no correlation with CPZ dose. The number of previous episodes was positively correlated with reaction time prolongation and negatively correlated with short-term verbal memory, consistent with a previous study suggesting that acute episodes cause specific cognitive reduction.

Adult↗

Neuropsychological effects of treatments for adults with cancer: a meta-analysis and review of the literature.

A meta-analysis was conducted to evaluate possible neuropsychological effects of treatments for cancer in adults. A search revealed 30 studies, encompassing 29 eligible samples, and leading to inclusion of a total of 838 patients and control participants. A total of 173 effect sizes (Cohen's d) were extracted across 7 cognitive domains and as assessed in the literature via 3 methods of comparison (post-treatment compared with normative data, controls, or baseline performance). Statistically significant negative effect sizes were found consistently across both normative and control methods of comparison for executive function, verbal memory, and motor function. The largest effects were for executive function and verbal memory normative comparisons (-.93 and -.91, respectively). When limiting the sample of studies in the analyses to only those with relatively "less severe" diagnoses and treatments, the effects remained. While these results point toward some specific cognitive effects of systemic cancer therapies in general, no clear clinical implications can yet be drawn from these results. More research is needed to clarify which treatments may produce cognitive decrements, the size of those effects, and their duration, while ruling out a wide variety of possible mediating or moderating variables.

Adult↗