Effect of cyclandelate on perception, memory and cognition in a group of geriatric subjects.
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This is a retrospective study of 100 child-patients with schizophrenia seen in the Child Psychiatric Clinic over a period of 4 years. Some personal and family characteristics of this group of patients are presented. Their clinical features, management and outcome are also presented and discussed.
Neurobehavioural deficits are commonly reported following treatment for childhood cancers. This study examined the impact of cranial irradiation (CRT) and chemotherapy in children, aiming to identify factors detrimental to long-term outcome. The study compared survivors of acute lymphoblastic leukemia (ALL), treated with CRT and chemotherapy (CRT group: n = 100), survivors of cancers treated with chemotherapy only (n = 50) and healthy controls (n = 100) for intelligence, academic achievement, information processing, learning, and executive function. CRT and chemotherapy in combination were associated with reduced intelligence, educational skill, immediate memory, processing speed, and executive function. Children treated with chemotherapy alone exhibited subtle information processing deficits. Within the CRT group, younger age at treatment was predictive of deficits in non-verbal ability, educational skills and executive functions. High dose CRT was associated with poorer information processing and lower arithmetic ability.
BACKGROUND: As human spaceflight missions extend in duration and distance from Earth, a self-sufficient crew will bear far greater onboard responsibility and authority for mission success. This will increase the need for automated fault management (FM). Human factors issues in the use of such systems include maintenance of cognitive skill, situational awareness (SA), trust in automation, and workload. This study examine the human performance consequences of operator use of intelligent FM support in interaction with an autonomous, space-related, atmospheric control system. METHODS: An expert system representing a model-base reasoning agent supported operators at a low level of automation (LOA) by a computerized fault finding guide, at a medium LOA by an automated diagnosis and recovery advisory, and at a high LOA by automate diagnosis and recovery implementation, subject to operator approval or veto. Ten percent of the experimental trials involved complete failure of FM support. RESULTS: Benefits of automation were reflected in more accurate diagnoses, shorter fault identification time, and reduced subjective operator workload. Unexpectedly, fault identification times deteriorated more at the medium than at the high LOA during automation failure. Analyses of information sampling behavior showed that offloading operators from recovery implementation during reliable automation enabled operators at high LOA to engage in fault assessment activities CONCLUSIONS: The potential threat to SA imposed by high-level automation, in which decision advisories are automatically generated, need not inevitably be counteracted by choosing a lower LOA. Instead, freeing operator cognitive resources by automatic implementation of recover plans at a higher LOA can promote better fault comprehension, so long as the automation interface is designed to support efficient information sampling.
BACKGROUND: Cognitive effects after cranial radiotherapy are widely discussed, but there is growing evidence that chemotherapy may also induce changes in neuropsychological functioning. This review summarizes the published literature regarding cognitive functioning after cancer therapy in adult patients. MATERIAL AND METHODS: 63 reports from January 1980 to July 2003 assessing objective cognitive effects of irradiation and/or chemotherapy by neuropsychologic evaluation were analyzed. 57 studies with 3,424 patients were included for evaluation. RESULTS: The results of this review confirm that both chemotherapy and irradiation can result in cognitive deficits. No clinically relevant differences are found for cognitive deficits, cognitive impairment rate, and single cognitive domains, when chemotherapy, cranial irradiation and combined radio- and chemotherapy were compared. Only 28 trials with 1,000 patients report quantitative data on patients with cognitive deficits after therapy. There are 44.1% (range 18-75%) of 451 patients in the chemotherapy group, 44.0% (range 29-83%) of 320 patients in the radiotherapy group, and 64.5% (range 30-100%) of 229 patients in the combined irradiation and chemotherapy group with cognitive deficits. Furthermore, cognitive functioning below average before chemo- or radiotherapy is found in subgroups of cancer patients. CONCLUSION: There is evidence of cognitive impairment in adult tumor patients after chemotherapy similar to effects after cranial irradiation. Cognitive functioning below average before therapy may be due to paraneoplastic effects. More prospective studies with a long-term follow-up using standardized neuropsychometric testing, assessment of premorbid intelligence, and suited control groups are needed.
This report presented results of psychological studies done during a double-blind study which compared sulthiame with diphenylhydantoin as primary agents in the treatment of uncontrolled epileptics. Assessments of intellectual, neuropsychological, and social functioning abilities were made with 22 adult epileptic patients. The results showed significantly less impairment with treatment by diphenylhydantoin than by sulthiame, and substantial differences were revealed on intellectual tasks, on tasks calling for sustained concentration and attention, and on psychomotor problem-solving tasks. The results could not be explained on the basis of increased tonic-clonic seizures while on sulthiame. However, an increase in other types of seizures was noted, as was an increase in EEG epileptiform discharges. Possible mechanisms for the decrement in performance were discussed, and the value of an objective assessment of the psychological effects of anticonvulsant agents was noted.
Twenty three children who had been treated for acute lymphoblastic leukaemia (ALL) were evaluated intellectually using the British Ability Scales. Their treatment included early cranial irradiation, intrathecal chemotherapy, and systemic chemotherapy. Nineteen children who had been treated for various types of solid tumours (ST), had undergone related chemotherapy, and had received irradiation to sites of the body other than the cranium were used as controls. In addition, patients' siblings were assessed and their scores statistically corrected to produce a best estimate of the patients' pre-morbid degree of intellectual functioning. The results showed intellectual deficits after treatment in both patient groups, but these were consistently larger in the ALL group, particularly for the higher functions of intelligence. Intellectual deficit in ALL patients did not show immediately after radiotherapy but became progressively more apparent some time afterwards and particularly in younger children. In contrast, in the ST group, intellectual deficits seemed to diminish over time, and the age at radiotherapy was not a critical factor.
Recently, biologically active therapeutic peptides have been artificially synthesized by genetic engineering techniques. These peptides are easily degraded under physiological conditions and also encounter absorption problems due to their high molecular weight. Hence, they cannot be utilized effectively in conventional dosage forms. For such active agents, new types of DDS must be developed to deliver the drug effectively to the target site (targeted, site-specific delivery) and release drug when drug is required (temporal control) in addition to conventional rate-controlling systems. To realize such drug release systems, it is important to construct a system where drug itself senses an environmental stimuli and responds to appropriately control drug release. Such systems are described as "intelligent DDS", as distinguished from conventional DDS.
A randomized concentration-controlled clinical trial (RCCCT) is an alternate experimental design to the standard dose-controlled study. In a RCCCT, patients are randomly assigned to predefined plasma or blood drug concentration ranges (low, medium, and high). With the caveat that concentration ranges are sufficiently separated, this design should enhance the ability to discover important concentration response relationships. FK-506, a potent and promising immunosuppressive agent for prevention and treatment of graft rejection, has shown significant clinical activity in some immune-mediated disorders. To implement the RCCCT design, a novel FK-506 intelligent dosing system (IDS) was used to guide all doses to prospectively achieve the target concentration range specific in the study protocol. Patients enrolled in these trials suffered from a variety of autoimmune disorders, including multiple sclerosis, primary biliary cirrhosis, psoriasis, autoimmune chronic active hepatitis, and nephrotic syndrome. We observed excellent predictive performance of the IDS for all patients. The accuracy (mean prediction error) of the IDS was -0.022 ng/ml and the precision (standard deviation of the prediction error) was 0.119 ng/ml. Thus, the IDS is both accurate and reproducible for autoimmune patients. We conclude that the RCCCT design, guided by an accurate and precise IDS, is an informative and cost-effective approach for evaluation of efficacy and safety of effective but highly toxic agents.
HIV infection (AIDS) burst upon the scene a decade ago. Because it is a sexually transmitted disease that infects blood and kills its victim, it is military relevant and will impact on all aspects of the military. The US Army Medical Research and Development Command as 'Lead Agent for Infectious Disease Research' in the Department of Defense has developed a comprehensive approach to address military concerns: surveillance of infection rates (intelligence) around the world and in the military; behavioural research to develop more effective means of education to change behaviour; and biological research to develop a quick and easy field test, and a vaccine or drug to prevent the disease from occurring despite exposure. Its success will influence the success of the Army in the future.
A number of neurological disorders including Alzheimer and Parkinson disease have been suggested to be caused by processes leading to lipid peroxidation. Other theories implicate the accumulation of damaged DNA, resulting from a defect in DNA repair, in the pathogenesis of these disorders. I suggest that these theories might be related, since the hydroxy free radical is known to attack DNA and inactivate enzymes so that oxygen metabolism has the potential to interfere with the maintenance of genomic integrity. Since psychometric intelligence correlates highly with erythrocyte glutathione peroxidase activity, a free radical scavenger, perhaps this might explain the marked intellectual impairment caused by chemotherapeutic agents such as cytosine arabinoside, as well as in Alzheimer disease.
The authors review 42 consecutive cases of benign astrocytic and oligodendrocytic tumors of the cerebral hemispheres in children undergoing surgery in the pediatric service of the Hôpital des Enfants Malades between 1975 and 1987. Epilepsy was the presenting sign in 76% of the children and remained the only clinical sign at diagnosis in 62%. Partial or complex partial seizures were observed in half of the cases, but other seizure types were also frequent. Diagnosis of the tumor as the etiological agent rested upon the results of computerized tomography or magnetic resonance imaging. Postoperative mortality (5%) and morbidity (16%) rates were low. The postoperative intelligence quotient was above 80 in 71% of the patients, and 77% of the children had no major problem in school. Although only two of the 42 patients were given postoperative radiotherapy, there were no recurrences in 82% of the survivors. The actuarial probability of nonrecurrence of the tumor was 95% at 5 years. Three patients with recurrent tumor underwent further surgery and are, at the present time, recurrence-free. The incidence of epilepsy fell from 76% before surgery to 19% after removal of the tumor alone; therefore, intraoperative electrocorticography and resection of the electrically abnormal cortex at the time of the first surgical procedure do not appear necessary. It is possible that tumor removal restores a mechanism that limits the spread of seizures and, thus, the clinical manifestations of epilepsy. Benign astrocytic and oligodendrocytic tumors of the cerebral hemispheres in children should not be treated with adjuvant radiotherapy, at least initially.
The purpose of this study was to investigate whether the intelligence quotient (IQ) in children treated for leukemia decreases in the years following whole brain irradiation. Twenty-seven leukemic children were assessed following a mean time lapse between radiotherapy and IQ measurement of 9 years. The IQ test used was the Hamburg Weschsler Intelligence Test for Adults. The IQ results did not differ significantly, p > 0.05, from the IQs of the general population. It was found that age and dose were not predictors of a decrease in IQ. The only predictor was time lapse between irradiation and IQ measurement, which we found to be indicative of an IQ decrease even after 9 years. Time lapse between irradiation is a useful predictor of IQ.
OBJECTIVE: Intractable epilepsy is related to various transient and chronic brain electric and neurochemical disturbances. There is increasing evidence that chronic epilepsy induces secondary neuronal metabolic and structural decline. However, there is no convincing evidence that the cognitive abilities of patients deteriorate with increasing duration of intractable epilepsy. METHODS: To examine whether duration of refractory temporal lobe epilepsy (TLE) is related to generalised cognitive impairment, psychometric intelligence based on the full scale intelligence quotient (FSIQ, WAIS-R) was determined in 209 patients with unilateral TLE. For analyses of variance (ANOVA) patients were grouped into three categories: <15, 15-30, and >30 years of refractory TLE. RESULTS: An ANOVA and a multiple regression analysis showed that duration of TLE affects FSIQ. Patients with >30 years of TLE performed worse than patients with 15 or 30 years of TLE. The factors side of seizure origin and type of lesion on MRI did not reach significance. A second ANOVA including education as factor showed that in patients with higher educational attainment, the mean FSIQ was stable for a longer duration of TLE than in less educated patients. Retesting 6 months after anterior temporal lobectomy seizure free patients (n=85 of 127) had an higher FSIQ but showed a similar duration effect before and after anterior temporal lobectomy. The variables age at epilepsy onset, education, frequency of interictal epileptiform discharges, frequency of habitual and generalised seizures, serum concentration of antiepileptic drugs, and polypharmacy were statistically controlled. CONCLUSIONS: Psychometric intelligence of patients with a longer duration of refractory TLE were most severely impaired. Consequently, refractory TLE seems to be associated with slow but ongoing cognitive deterioration. It is assumed that epilepsy related noxious events and agents exhaust the compensatory capacity of brain functions. However, as in dementia and Alzheimer's disease, higher educational attainment as an indicator of higher brain reserve might delay the cognitive decline.
Antimicrobial resistance (AMR) represents a major global public health concern, rendering available antimicrobials ineffective and leading to infections that are difficult to treat. Artificial intelligence (AI) has been increasingly applied across the AMR continuum, including resistance prediction, rapid diagnostics, new antimicrobial discovery, drug repurposing, antimicrobial surveillance, and clinical decision support. In this review, we aim to highlight recent developments in the use of artificial intelligence (AI) to address antimicrobial resistance (AMR). In addition, we review computational methods that help interpret genomic, phenomic, clinical, and epidemiological data to support the development of treatment strategies and novel antimicrobial agents. The key issues addressed include data quality, model interpretability, external validation, regulatory requirements, privacy, and fairness. While AI is not a complete solution to AMR, it can certainly strengthen the global AMR response by complementing key areas of AMR such as antimicrobial stewardship, infection prevention, laboratory diagnostics, and global surveillance.
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