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Biomedical subjects

J Overall

Publications and source records attributed to J Overall.

11 recordsLinked to original sources

The Alzheimer's disease activities of daily living international scale (ADL-IS).

BACKGROUND: Activities of daily living (ADL) deficits are integral components of dementia disorders, and ADL measures are among the most robust markers of the course of Alzheimer's disease (AD). Despite this acknowledged importance, no clearly useful ADL instrument for cross-cultural application in pharmacologic trials in the early stages of AD had been available. METHOD: An international effort was launched to develop an ADL scale for pharmacologic trials in early AD. Steps taken from 1990 to the present included: (1) international scientific working group meetings and reviews, (2) reviews of existing measures, (3) collating of existent, nonredundant items, (4) querying experts for new items, (5) interviews with informants and subjects in the USA, France, and Germany, toward the identification of potential new items, (6) identification of an item pool based upon these procedures, (7) creation of a trial instrument, (8) piloting of this instrument, and (9) refinement of the scale based upon statistical analysis of the pilot data. Final item selection was based upon: (1) relevance for > or = 80% of subjects in severity-stratified USA and German samples; (2) absence of gender and national biases; (3) significant (p <.05) discrimination between (a) normal versus mildly impaired and (b) mildly impaired versus moderately to moderately severely impaired subjects; and (4) Global Deterioration Scale (GDS) scores accounting for > or = 12% of variance in the item after controlling for age and gender. RESULTS: An ADL scale consisting of 40 items that correlate with the global and cognitive progress of AD is developed for international usage in pharmacologic trials in incipient, mild, moderate, and moderately severe AD. The scale contains 40 items falling within 13 ADL categories. The 40-item scale is shown to have .81 correlation with GDS staging, .81 with mental status assessment (Mini-Mental State Examination), and .81 with a psychometric test (the SKT) (p values < .001). CONCLUSION: This scale can be used to measure therapeutic response in AD.

Activities of Daily Living↗

Reproducibility of regional brain metabolic responses to lorazepam.

UNLABELLED: Changes in regional brain glucose metabolism in response to benzodiazepine agonists have been used as indicators of benzodiazepine-GABA receptor function. The purpose of this study was to assess the reproducibility of these responses. METHODS: Sixteen healthy right-handed men underwent scanning with PET and [18F]fluorodeoxyglucose (FDG) twice: before placebo and before lorazepam (30 micrograms/kg). The same double FDG procedure was repeated 6-8 wk later on the men to assess test-retest reproducibility. RESULTS: The regional absolute brain metabolic values obtained during the second evaluation were significantly lower than those obtained from the first evaluation regardless of condition (p < or = 0.001). Lorazepam significantly and consistently decreased both whole-brain metabolism and the magnitude. The regional pattern of the changes were comparable for both studies (12.3% +/- 6.9% and 13.7% +/- 7.4%). Lorazepam effects were the largest in the thalamus (22.2% +/- 8.6% and 22.4% +/- 6.9%) and occipital cortex (19% +/- 8.9% and 21.8% +/- 8.9%). Relative metabolic measures were highly reproducible both for pharmacologic and replication condition. CONCLUSION: This study measured the test-retest reproducibility in regional brain metabolic responses, and although the global and regional metabolic values were significantly lower for the repeated evaluation, the response to lorazepam was highly reproducible.

Adult↗

Depression of thalamic metabolism by lorazepam is associated with sleepiness.

Though it is well recognized that the pharmacological actions of benzodiazepines are mediated by facilitation of GABAergic neurotransmission, the consequences of these changes in regional brain function are not well understood. This study measured regional brain glucose metabolism using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose in normal controls (n = 21) investigated with and without lorazepam (30 micrograms/kg IV) and with flumazenil given after lorazepam (n = 9). Lorazepam markedly decreased metabolism in thalamus (23 +/- 8%) and occipital cortex (19 +/- 8%), and flumazenil partially reversed these changes. Changes in metabolic activity in thalamus were significantly correlated with lorazepam-induced sleepiness (r = .69, df 20, p < .0005) and there was a trend of an association between the reversal by flumazenil of lorazepam-induced change in thalamus and in sleepiness (r = .63, df 8, p = .07). Benzodiazepine-induced changes in thalamic activity may account for their sedative properties.

Adult↗

Test-retest reliability of the P50 mid-latency auditory evoked response.

Attenuation in mid-latency auditory evoked responses (MLAERs) can be used to study sensory gating. If paired-click stimuli (S1 and S2) are used, lower amplitude in response to S2 vs. S1 (attenuation) is considered evidence for intact sensory gating. However, the need for reliable measurements of MLAER amplitude and attenuation is a recognized problem. Ten normal volunteers were studied six times each. An S1 amplitude test-retest reliability coefficient (r) of 0.585 was obtained when means of two recordings were used vs. reliability coefficients as high as 0.809 for means of six recordings. Averaging a higher number of runs (120 vs. 60) resulted in a reliability coefficient of 0.677/recording. Similar values were obtained for S1 and S2 latencies. Reliability coefficients for S2 attenuation (S2/S1) were not nearly as high (a value of 0.138 when means of all six recordings were used). The S1 amplitude as measured in this study (with 120 averages) appears to be a reliable psychophysiologic measurement, but the S2/S1 attenuation measure is more variable, perhaps reflecting a greater sensitivity of the S2/S1 to uncontrolled variables in this study. Further research to identify such variables is necessary.

Adult↗

Replication and extension of P50 findings in schizophrenia.

In a paired click "conditioning (S1), Testing (S2)" paradigm the amplitudes of responses to (S1) as well as the degree of attenuation of S2 as compared to S1 (S2/S1) were studied in two schizophrenic groups. Thirteen undifferentiated/disorganized (US) and thirteen paranoid (PS) patients were compared to thirteen age and sex matched normal volunteers. The US patients had significantly lower (S1) response amplitudes (P less than 0.001), as well as degree of attenuation of the response to (S2) (P less than 0.001) than the other two groups. No significant differences were found between the PS and N groups. Our data replicates the prior finding of decreased attenuation of the amplitude of the P50 wave in a paired click paradigm in schizophrenia. In addition, we showed that this phenomenon is significant mainly in the disorganized/undifferentiated patients as compared to the paranoid schizophrenics.

Evoked Potentials, Auditory↗

Brain organization in schizophrenia.

Brain metabolism was measured with positron emission tomography and [11C]deoxyglucose during baseline and during a visual task in 12 normal subjects and 18 schizophrenic patients. Global measures of metabolism for 11 brain regions were transformed into relative values by dividing them by the metabolic value for whole brain. Factor analysis was accomplished on the matrix of intercorrelations among the relative regional values for the normal and for the schizophrenic patients under baseline and under the task. Four factors that revealed independently varying metabolism in frontal, occipital, left-versus-right hemisphere, and subcortical structures were obtained. The frontal and subcortical factors discriminated between normal subjects and schizophrenic patients, whereas the occipital factor discriminated between baseline and task. Although activity in these individual regions varied significantly, it was the pattern of differences in regional metabolic activity that best discriminated between diagnostic groups and testing conditions.

Adult↗

Nursing home care as an alternative to psychiatric hospitalization. A Veterans Administration cooperative study.

Nursing homes have played a major role in deinstitutionalization, and their increased use for the mentally ill has been questioned. We performed a controlled study of nursing homes as an alternative to continued psychiatric hospitalization. Men (N = 403) referred for nursing home placement from eight Veterans Administration medical centers were randomly assigned to community nursing homes (CNHs), Veterans Administration nursing care units, continued care on the same ward, or transfer to another psychiatric ward. Patients met defined criteria for schizophrenia or organic brain disease. Data were collected before random assignment and six and 12 months later, covering physical and mental function, psychopathology, mood, social adjustment, satisfaction with care, as well as drug use, characteristics of settings, and movement in and out of settings. Significant differences between settings were found in self-care, behavioral deterioration, mental confusion, depression, and satisfaction with care. Results were strikingly consistent, showing the group transferred to another ward doing better and the CNH group doing worse. Drug use did not differ from six months before entering the study or later between the settings. Cost showed a marked advantage for the CNH group. Thus, the less costly community nursing home alternative must be viewed in the context of the nonmonetary costs of less favorable patient outcome.

Aged↗

Vidarabine therapy for mucocutaneous herpes simplex virus infections in the immunocompromised host.

Eighty-five immunocompromised patients were entered into a randomized, controlled, crossover study of mucocutaneous herpes simplex virus (HSV) infections. Thirty-nine patients (group A) received vidarabine for seven days followed by placebo for an additional seven days. Forty-six patients (group B) received the reverse regimens. Therapy did not significantly accelerate healing for the total population as assessed by loss of virus from lesions, cessation of lesion formation, and time to crusting. Group A patients demonstrated accelerated loss of pain from lesions (P = 0.0099) and defervescence (P = 0.03). Patients in group A who had HSV type 1 (HSV-1) infections or who were over 40 years of age did clear virus from lesions more rapidly (P = 0.04 and P = 0.03, respectively). No toxicity or significant adverse effects could be attributed to vidarabine administration. Benefit from vidarabine therapy is limited to immunocompromised patients over 40 years of age with HSV-1 infections.

Adolescent↗

Physostigmine: effects on cognition and affect in normal subjects.

Physostigmine was given intravenously to a total dose of 3 mg to 13 subjects; a placebo of 0.25 N saline was given intravenously to 10 other subjects; both groups received 1 mg of methscopolamine bromide subcutaneously preceding the intravenous infusions. A "physostigmine syndrome" consisting of decreased speech, slowed thoughts, mild sedation, expressionless faces, nausea, and decreased spontaneous activity was evident following doses of 1.5 to 2.0 mg of physostigmine. The capacity of short-term memory (STM) as measured by digit span tasks was significantly less for the subjects who received physostigmine than for the subjects who received placebo. No difference was observed between the two groups on tasks of consolidation from STM to long-term memory (LTM). Subjects who received physostigmine did not significantly differ from subjects who received placebo in their mood. However, two subjects in the physostigmine group, and no subjects in the saline group became tearful and depressed.

Adult↗