Neuropsychological Performance and Treatment Outcome in Male Alcoholics

Commonly used neuropsychological tests were administered to 91 detoxified alcoholics at the beginning of treatment. Statistically significant relationships were observed between test scores and post treatment consumption determined 8 months after completing treatment for 72 patients. The results varied depending upon the particular measure of posttreatment consumption evaluated and the type of statistical analysis used. The most consistent relationships were often counter to the notion that increased neuropsychological performance is correlated with a more favorable treatment outcome. Neuropsychological evaluation is of limited clinical utility in predicting posttreatment alcohol consumption.     

Tissue collection for correlative studies in childhood cancer clinical trials: ethical considerations and special imperatives.

Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families.     

Quantitative analysis of surface EMG activity of cranial and leg muscles across sleep stages in human.

OBJECTIVE: The aim of this study was to make a quantitative analysis of the changes in cranial and limb muscle activity from wakefulness to light and deep sleep stages and during rapid eye movement (REM) sleep of normal subjects. METHODS: Polysomnographic recordings were made of the sleep of 9 healthy human subjects, including electromyograms of the suprahyoid, temporalis and masseter cranial muscles and the anterior tibialis limb muscle. Quantitative assessments of EMG activity were carried out with root mean square (RMS) and frequency-spectral analysis (FSA) methods. RESULTS: From wakefulness to sleep, a significant reduction (-25.2 to -71.2%; P < 0.01) was observed in EMG activity (for both RMS and FSA) of the 3 cranial muscles using both methods of analysis. The EMG activity of suprahyoid muscle further decreased from non-REM to REM sleep (-17.8 to -43.0%; P < 0.01). In contrast, the EMG activity of the anterior tibialis muscle was only slightly reduced across sleep stages and did not further reduce during REM sleep. During REM sleep, all the 4 muscles maintained minimal activity. CONCLUSIONS: The maintenance of muscle activity during REM sleep suggests that a minimal level of activity is required to preserve physiological functions (e.g. airway patency, posture) related to homeostasis and bodily protection. SIGNIFICANCE: This study suggests that quantitative sleep EMG analysis is important for understanding the mechanisms of sleep-related movement disorders or when objective assessment of changes in EMG activity are needed for diagnostic purposes or for the assessment of drug efficiency.     

Inhibitory motor control in children with attention-deficit/hyperactivity disorder: event-related potentials in the stop-signal paradigm.

BACKGROUND: The aim of the study was to investigate the inhibitory control of an ongoing motor response and to identify underlying neural deficiencies, manifested in event-related potentials, that cause poorer inhibitory performance in children with attention-deficit/hyperactivity disorder. METHODS: A stop-signal paradigm with a primary visual task and auditory stop signal was used to compare performance in 13 children with attention-deficit/hyperactivity disorder and 13 control children, while event-related potentials were recorded simultaneously. RESULTS: Children with attention-deficit/hyperactivity disorder showed poorer inhibitory performance through a slower inhibitory process. Inhibitory processing of auditory stop signals was marked by a frontal N2 component that was reduced in the attention-deficit/hyperactivity disorder group relative to controls. A central positive component (P3) was associated with the success of inhibiting a response, but there were no group differences in its amplitude or latency. CONCLUSIONS: Findings support the hypothesis of deficient inhibitory control in children with attention-deficit/hyperactivity disorder. Slower inhibitory processing appears to be due to a specific neural deficiency that manifests in the processing of the stop signal as attenuated negativity in the N2 latency range.     

Sequence specificity of mutation induced by the anti-tumor drug cisplatin in the CHO aprt gene

Cis-diammine dichloroplatinum (cisplatin) is an effective anticancerdrug which forms adducts with DNA, in both bacterial and mammaliancells. It is suspected of producing tumors as well. To determinethe molecular nature of geneti alterations induced by cisplatin,we cloned and sequenced cisplatin-induced mutants in the adeninephosphoribosyl-transferase (aprt) gene of Cinese hamster ovary(CHO) cells. Mutation by cisplatin appears to be targeted asthe sites of mutation are consistent with the known bindingspecificity of cisplatin. Many mutations occur at or proximalto the sequence 5'-AGG-3' and 5'-GAG-3' and include transversions,transitions, frameshifts and short deletions and duplications.Several double changes were also observed. No major rearrangementswere recovered in our collection. At several locations, a numberof mutants were found to be clustered within a small targetregion, but unlike traditional hotspots, tese represent diversechanges occurring in a localized region of a few base pairs.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

“Avoidable mortality” as an index of health care outcome: Results from the european community atlas of “Avoidable death”

The history of the European Community Atlas of “Avoidable Death” is given. Data from the second Atlas are presented. For all causes of death except asthma there was a decrease in mortality in the period 1980–1984 with respect to 1974–1978. Taking the EC as a whole as the standard (100) population the standardised mortality ratio (SMR) in Ireland in the period 1980-1984 for tuberculosis was 160, for asthma 180 and maternal mortality 58. Ireland had the highest mortality for tuberculosis in both time periods. Asthma mortality increased in all countries except Scotland between 1974–1978 and 1980–1984. Ireland had one of the highest declines in maternal mortality over the two time periods. Within Ireland tuberculosis mortality was highest in the Mid-Western Health Board and lowest in the North-Western Health Board. Asthma mortality was highest in the Western Health Board and lowest in the Mid-Western Health Board. Maternal mortality was highest in the Midland Health board and lowest in the Southern Health Board.     

Presurgical electroencephalographic patterns and outcome from anterior temporal lobectomy.

We reviewed data from 48 patients after anterior temporal lobe resection for medically intractable epilepsy. All had ictal electro-encephalographic (EEG) evidence of unilateral temporal lobe onset. Depth electrodes were used in 19 patients. Successful surgical outcome correlated significantly with factors that suggested a temporal lobe focus, particularly in the interictal scalp EEG. The most successful outcome occurred in patients with well-localized unilateral interictal temporal spikes (100% improved). The group with well-localized bilateral temporal spikes also did well (76% improved). Patients with extratemporal spread of the interictal spike on scalp EEG, either unilaterally or bilaterally, did less well. Only one third improved, despite extensive extracranial and intracranial monitoring, when indicated. The interictal scalp EEG may be the only EEG necessary for the presurgical evaluation of selected patients with intractable temporal lobe epilepsy.