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Improvement of brain function in hemodialysis patients treated with erythropoietin.

To evaluate the effects of recombinant human erythropoietin (rHuEPO) on brain function, 15 chronic hemodialysis patients were studied by event-related P300, stimulus-related evoked potentials, and trailmaking before (hematocrit 22.7%) and after rHuEPO (hematocrit 30.6%). P300 peak latency elicited by a tone discrimination paradigm improved (391 before vs. 366 ms after; Cz = vertex; P less than 0.01) confirming beneficial effects on cerebral cognitive processing. P300 amplitude (13.6 vs. 15.8 microV; P = 0.06) and trailmaking tended to improve (55 vs. 43 s). P300 measures were influenced by low hemoglobin levels before rHuEPO (P less than 0.01), suggesting that severe anemia may contribute to uremic brain dysfunction. Furthermore, decrease of stimulus-related auditory brainstem I-V interpeak latency (4.28 before vs. 4.17 ms after; P less than 0.05) and increase of somatosensory N20/P25 amplitude (4.8 vs. 7.0 microV; P less than 0.05) pointed to improvement of sensory pathways by mechanisms unrelated to cognition. Brain dysfunction in chronic hemodialysis patients may, beside other factors, in part be caused by severe anemia and can be improved by rHuEPO treatment.

Anemia↗

Role of dehydration in heat stress-induced variations in mental performance.

Variation in mental performance under different levels of heat stress-induced dehydration was recorded in 11 subjects heat acclimatized to the tropicals. Dehydration was induced by a combination of water restriction and exercise in heat. The psychological functions--arithmetic ability, short-term memory, and visuomotor tracking--were assessed in a thermoneutral room after the subjects recovered fully from the effects of exercise in heat, as reflected by their oral temperature and heart rate. The results indicated significant deterioration in mental functions at 2% or more body dehydration levels.

Adult↗

Frontal lobe dysfunction and false memory susceptibility in older adults.

The study reported here was conducted to examine the role of frontal lobe function in false memory susceptibility in older adults, as little research has specifically examined this question in older adults. False recognition was compared in three groups of older adults (one with no evidence of cognitive impairment, one with evident frontal impairment but no other dysfunction, and an Alzheimer's dementia group) to a single group of young adults. Results indicate that false memory susceptibility was highest in the frontally impaired group, with young and older control participants performing similarly. In contrast, Alzheimer's dementia patients showed relatively low levels of false memory susceptibility, likely due to overall poor memory for list items, indicating that general memory impairments are not likely to be driving false memory susceptibility. Potential mechanisms underlying these effects are discussed.

Adult↗

Conversational discourse abilities following severe traumatic brain injury: a follow-up study.

The major aim of this study was to describe the conversational abilities of a group of severely injured TBI speakers, at a minimum of 2 years post-injury. The association between conversational impairment and (a) selected measures of executive function and (b) psychosocial handicap was also examined. Twenty-four members of the group of 26 severely injured TBI speakers who had initially been assessed between 3 and 6 months post-injury were reviewed at a minimum of 2 years post-injury (mean = 2 years, 10 months). At initial assessment, TBI speakers were compared with non-TBI orthopaedic patients and with a group of university students. At follow-up, however, they were compared only with the orthopaedic patients. Conversational assessment was carried out using a modified form of Damico's Clinical Discourse Analysis. As a group, the TBI speakers' conversational abilities did not improve over time. There was, however, a subgroup (n = 8) of speakers who did improve, and these could be distinguished by greater initial severity of injury and a significantly longer period of speech-language pathology intervention than the speakers who either remained the same or worsened over time. Modest associations between conversational discourse skills and measures of executive function and a measure of psychosocial handicap were identified. These findings indicate that disruptions in conversation persist into the longer term. More assiduous efforts may need to be made to (a) identify subtle discourse changes in the early months after injury and (b) engage TBI speakers in speech-language pathology services. Such services are also required over a longer time frame, in community-based models of service provision.

Adolescent↗

A multidimensional comparison of morphine and hydromorphone patient-controlled analgesia.

Although patient-controlled analgesia (PCA) pumps have been in use for more than a decade, the optimal PCA analgesic has yet to be identified. Many drugs are used; however, morphine remains the "gold standard" of opioid analgesics worldwide. The present study evaluated morphine and hydromorphone (Dilaudid) PCA with respect to analgesic efficacy, side effects, mood, and cognitive function. Sixty-one opioid naive patients undergoing lower abdominal surgery participated in the double-blind protocol. Verbal rating scores, use of medication, and side effects for the two medications were recorded. Cognitive functioning was assessed by computation of Digit Symbol and Trails Making B Tests. Self-reported affective state (mood) was measured by Profile of Mood States (POMS) inventory. Both medications provided adequate analgesia without a difference in side effects. Cognitive performance was poorer in the hydromorphone group (P < 0.05). Patients receiving hydromorphone reported less anger/hostility (P < 0.01) and generally better mood elevations on the other subscales than those receiving morphine. A similar incidence of side effects and dose medication can be anticipated with morphine and hydromorphone. When considering cognitive effects, morphine had less adverse consequences, while hydromorphone appeared to result in improved mood. We conclude that hydromorphone may provide a suitable alternative to morphine.

Abdomen↗

Factors associated with perceived quality of life many years after traumatic brain injury.

OBJECTIVES: To explore factors associated with perceived quality of life (QOL) 8 to 24 years after traumatic brain injury (TBI). DESIGN: Retrospective cohort study. PARTICIPANTS: Two hundred seventy-five individuals who sustained moderate to severe TBI who were discharged from a rehabilitation hospital participated in this study. We interviewed consenting participants up to 24 years after injury. OUTCOME MEASURES: Self-rated Quality of Life Scale. RESULTS: Multivariate linear regression analyses revealed that perceived mental health, self-rated health, gender (women rating QOL higher), participation in work and leisure, and the availability of emotional support were significantly associated with QOL (P <.05). CONCLUSION: The importance of designing ongoing support programs to further reintegrate TBI survivors several years after injury is discussed.

Adolescent↗

Quality of life of elderly patients with isolated systolic hypertension: baseline data from the Syst-Eur trial. Syst-Eur Trial Investigators.

OBJECTIVE: To describe measures of quality of life of elderly patients with isolated systolic hypertension at entry to a placebo-controlled randomized trial of antihypertensive treatment and to investigate factors associated with these. DESIGN: Cross-sectional analyses at entry to a randomized controlled trial. SETTING: Patients attending hypertension clinics or general practitioners' surgeries at 30 centres in 10 European countries. PATIENTS: Six hundred and thirty-one patients aged 60 years or more, with a sitting systolic blood pressure during the run-in phase of 160-219 mmHg, a sitting diastolic blood pressure below 95 mmHg and a standing systolic blood pressure of 140 mmHg or more. MAIN OUTCOME MEASURES: Cognitive function tests (Reitan Trail Making A and B), Brief Assessment Index (a measure of depressed mood) and four subscales from the Sickness Impact Profile (Ambulation, Social Interaction, Sleep and Rest and Housework). RESULTS: Poor quality of life was generally associated with increasing age, previous treatment with antihypertensive drugs, presence of cardiovascular complications and, among women, high diastolic blood pressure, higher consumption of alcohol and high body mass index. CONCLUSIONS: At entry to the trial there was considerable heterogeneity of patients in terms of measures of quality of life and cognitive performance. It remains to be determined whether these influence subsequent quality of life during randomized treatment.

Age Factors↗

Glycaemic thresholds for hypoglycaemic symptoms, impairment of cognitive function, and release of counterregulatory hormones in subjects with functional hypoglycaemia.

Nine patients with food-relieved hypoglycaemic symptoms, in whom insulinoma and other organic diseases presenting with hypoglycaemia had been ruled out, and nine matched controls, participated in the study. Subjects were studied during a 5-h controlled (Biostator) insulin-induced (1-2 mU kg-1 min-1) hypoglycaemic clamp. After 1 h of euglycaemia, we aimed to lower the glucose level in arterialized venous blood in a stepwise manner at 30-min intervals to 3.5, 3.0, and 2.0 mmol l-1, and to withhold these levels for a further 30 min. At euglycaemia and at the end of the latter steps, the visual reaction time and cognitive function (digit span, letter cancellation and trail making) were tested, together with recording symptoms and signs of hypoglycaemia. Counter-regulatory hormones were measured at 20-min intervals. In the patients, clinical signs and symptoms of hypoglycaemia developed at median blood glucose levels of 2.6-2.8 and 2.8-3.1 mmol l-1, respectively. By contrast, the blood glucose levels were 0.4-0.8 mmol l-1 lower in control subjects (P less than 0.05). Similarly, the median threshold for deterioration of visual reaction time was 2.8 mmol l-1 in patients and 2.1 mmol l-1 in controls (P less than 0.01). A similar trend was observed for the results of the neuropsychological tests. Visual reaction time deteriorated in all subjects, whereas the cognitive function of some of the subjects in each group remained unchanged during hypoglycaemia. The glycaemic thresholds for release of cortisol, glucagon and growth hormone were significantly higher in patients (P less than 0.05), whereas the thresholds for catecholamine release showed no significant difference from controls. Despite the comparable glucose infusion rates required to sustain each of the hypoglycaemic levels in the two groups, the control subjects achieved lower glucose levels, suggesting that there is resistance to insulin or glucose in functional hypoglycaemia. In conclusion, the present study suggests that the existence of a higher threshold for symptoms and signs, as well as for deterioration of brain function, may explain every-day hypoglycaemic symptoms, despite normal glucose levels, in subjects with functional hypoglycaemia. However, the hypothesis should be tested further using a blinded approach, including euglycaemic control studies.

Adult↗

Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor.

The purposes of the present studies were to examine the androgen receptor (AR) binding ability and in vitro functional activity of multiple series of nonsteroidal compounds derived from known antiandrogen pharmacophores and to investigate the structure-activity relationships (SARs) of these nonsteroidal compounds. The AR binding properties of sixty-five nonsteroidal compounds were assessed by a radioligand competitive binding assay with the use of cytosolic AR prepared from rat prostates. The AR agonist and antagonist activities of high-affinity ligands were determined by the ability of the ligand to regulate AR-mediated transcriptional activation in cultured CV-1 cells, using a cotransfection assay. Nonsteroidal compounds with diverse structural features demonstrated a wide range of binding affinity for the AR. Ten compounds, mainly from the bicalutamide-related series, showed a binding affinity superior to the structural pharmacophore from which they were derived. Several SARs regarding nonsteroidal AR binding were revealed from the binding data, including stereoisomeric conformation, steric effect, and electronic effect. The functional activity of high-affinity ligands ranged from antagonist to full agonist for the AR. Several structural features were found to be determinative of agonist and antagonist activities. The nonsteroidal AR agonists identified from the present studies provided a pool of candidates for further development of selective androgen receptor modulators (SARMs) for androgen therapy. Also, these studies uncovered or confirmed numerous important SARs governing AR binding and functional properties by nonsteroidal molecules, which would be valuable in the future structural optimization of SARMs.

Anilides↗

Cerebral function in hyperthyroid patients. Psychopathology, psychometric variables, central arousal and time perception before and after thyreostatic therapy.

Psychopathology, psychometric variables, central arousal and time experience were studied in 30 hyperthyroid female outpatients. While these patients could be significantly discriminated in several of the above-described measures during the acute state of the disease, the intergroup differences disappeared after thyreostatic therapy. The thyroxine level was correlated with elevated beta-activity and the latter with variables of psychopathology and time experience. Hormonal dysbalance in hyperthyroidism is discussed as a biological substrate for neurophysiological changes which in turn causes deterioration in mood and behavior.

Adult↗

Neuropsychological and EEG disturbances in polydrug users.

EEG and neuropsychological evaluation of 66 polydrug users revealed that 43% had EEG abnormalities and 45% had neuropsychological impairment 3 weeks after admission to a polydrug study unit. At 5-month follow-up, 27% of 30 retested subjects were still impaired neuropsychologically. Impairment may be related to extensive involvement with sedatives, alcohol, or heavy polydrug use. The authors suggest that cerebral dysfunction in polydrug users might be the result of organicity of intermediate duration and that deficits may be experienced by some beyond 5 months of reduced use or abstinence. Organicity may dictate structured, reality-based intervention techniques, especially early in treatment.

Adolescent↗

Insight and its relationship to violent behavior in patients with schizophrenia.

OBJECTIVE: Lack of insight affects the management of schizophrenia. The interrelationship between lack of insight and illness attributes in patients with schizophrenia who commit violent acts is important and underresearched. METHOD: One hundred fifteen violent patients with schizophrenia in a jail or court psychiatric clinic were evaluated on measures of symptoms, illness severity, insight into illness, and the legal consequences of their illness ("forensic insight"). A sample of nonviolent patients served as a comparison group. RESULTS: Compared with the nonviolent cohort, violent patients were more symptomatic, had poorer functioning, and had a more prominent lack of insight. Deficits of insight into illness coexisted with a lack of forensic insight, which was also associated with psychosis. CONCLUSIONS: Patients with schizophrenia who commit violent acts have insight deficits, including lack of awareness of the legal implications of their behavior. Targeted interventions to improve insight and treatment compliance in this population are warranted.

Adult↗

Patterns of cognitive performance in middle-aged and older adults: A cluster analytic examination.

Cognitive decline in speeded abilities, executive function, and memory is believed to typify normal aging. However, there is significant variability in cognitive function with advanced age and some reports of relatively intact cognitive function among a subset of older individuals. The present study consists of a cluster analysis to examine the patterns of cognitive function in middle-aged and older individuals. Analyses revealed 3 clusters of middle-aged adults, including an intact group, persons with poor motor speed, and a group with reduced executive function. Three clusters were also identified for older adults, including a group with poor executive function, persons with reduced speed performance (attention, executive function, motor), and a group with global cognitive decline. No evidence emerged for a cluster of older adults with intact performance in all domains or with isolated memory deficits. Findings generally support the frontal aging hypothesis and may provide important information about healthy cognitive aging.

Adult↗

Tactile-perceptual functioning as a factor in general psychological abilities.

This investigation was designed to study the influence of simple sensory perceptual ability (tactile perception) on various human abilities such as language acquisition, visuo-spatial problem solving, concept formation, motor skills, memory, and learning. Children with documented evidence of impaired brain functions (seizure disorder and corresponding EEG abnormality) and children without evidence or suspicion of neurological impairment were examined. The results suggest that tactile perceptual ability exerts a significant effect on the adequacy of a broad range of human abilities.

Adolescent↗