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Biomedical subjects

C A Sandman

Publications and source records attributed to C A Sandman.

At least 73 records · Page 4Linked to original sources
PubMed1985

Disregulation of hypothalamic-pituitary-adrenal axis in the mentally retarded.

Previous reports of cognitive and social improvement in the mentally retarded after administration of MSH/ACTH fragments suggested disregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The current study examined the integrity of this system with the Dexamethasone Suppression Test (DST). The DST is a biological index of HPA integrity and recently has been used as a diagnostic aid for endogenous depression. Thirty-five mentally retarded patients were administered 1 mg of dexamethasone just after a sample of blood was taken. Blood samples were analyzed for cortisol by RIA at 11:00 p.m. (basal), 8:00 a.m., 4:00 p.m., and 10:00 p.m. Between 40% and 48% (depending on sampling) of the patients failed to suppress cortisol (greater than 4 micrograms/dl), after the DST challenge. The results suggested that a significant proportion of mentally retarded patients have a DST index reflecting a disordered HPA axis and complements earlier studies of cognitive enhancement observed after treatment with MSH/ACTH fragments. The possibility that the stress of hospitalization was related to a disordered HPA was suggested. The possible co-existence of depression in the mentally retarded invites further study.

Adult↗
PubMed1985

The relationship of endogenous ACTH levels to visual-attentional functioning in patients with congenital adrenal hyperplasia.

The within subject experimental approach of either doubling cortisone medication dose or withdrawing steroid treatment for 36 hr preceding behavioral testing was found to induce corresponding significantly elevated or suppressed plasma ACTH levels, as measured by radioimmunoassay, in six of eight adults diagnosed as having congenital adrenal hyperplasia (CAH). During the session characterized by elevated ACTH levels, the CAH patients exhibited significantly reduced median reaction times on the Sternberg Item Recognition Task. Their response pattern was suggestive of facilitated visual attentional functioning and/or overt motor response capacity rather than alteration of simple cognitive processing. Moreover, Sternberg performance was significantly correlated with endogenous ACTH levels but not with levels of plasma cortisol or cortisone replacement medication. This enhancement of performance paralleled a previous finding of improved performance on the Sternberg paradigm by normal adults following exogenous administration of ACTH 4-10 (Ward et al., 1979). Further analysis of the Sternberg performance suggests that other variables such as mineralocorticoid treatment, type of CAH impairment, and sex may act to moderate the degree of ACTH-related facilitation on this task. Performance on other visual and verbal attention and memory tasks, found earlier to be sensitive indices of exogenous administration of ACTH 4-10 and related fragments, was not significantly altered by manipulation of endogenous ACTH levels in these CAH patients.

Adolescent↗
PubMed1985

Paradoxical excitement to sedative-hypnotics in mentally retarded clients.

The relationships among "paradoxical" excitement to sedative--hypnotic medication, self-injurious behavior, and perinatal trauma were evaluated. Mentally retarded patients were classified as either paradoxical or normal responders to sedative-hypnotics. Paradoxical responders to these medications have a lower MA, a history of perinatal trauma, self-injurious behavior (SIB), and aggressive behavior when compared to normal responders. These findings confirmed and extended previous reports that a type of SIB may be indexed by paradoxical response to sedative-hypnotics. Results also suggested that perinatal trauma may be of etiological importance in the development of SIB. Because perinatal trauma or fetal distress results in excessive levels of B-endorphin, in utero, an impaired endogenous opiate system may be a critical factor maintaining a syndrome of SIB. Thus, these data may indicate psychopharmacological markers of SIB that may have both treatment and etiological significance.

Adolescent↗
PubMed1984

Is there an evoked vascular response?

Event-related potentials of the brain are enhanced when stimulation is synchronized with diastolic phases of cerebral or cephalic pulse pressure waves. A cerebral vascular event has been found to be temporally consistent with the event-related potential. Averaged evoked vascular responses were measured with bioimpedance techniques from the brain and the arm. Changes in brain blood volume occurred 150 to 250 milliseconds after stimulation synchronized with diastolic but not systolic phases of the cerebral pulse pressure wave. The time course of this phenomenon defies the usually accepted characteristics of metabolic activity. The evoked vascular response may be a neurally mediated event in anticipation of altered metabolic demand, and it offers the possibility of measurement in real time.

Animals↗
PubMed1984

Augmentation of the auditory event related potentials of the brain during diastole.

Previous studies demonstrated that stimuli synchronized with systolic and diastolic phases of the pulse pressure wave enhanced the visual event related potentials (ERPs) of the brain. The present study extended these observations to the auditory ERP in passive and attentional conditions. Pure tones were synchronized with systolic and diastolic phases of the cephalic and palmar arteries. During one condition, subjects were paid a bonus for reporting accurately the number of times they heard a tone (attention condition) and in a second condition they listened passively (non-attend). Stimuli synchronized with the diastolic phase, reliably produced augmentation of the N1 component across all conditions. The N2 component was smaller in the right hemisphere of attentive subjects when stimulation was synchronized with diastole. These results were discussed in the context of the cognitive psychophysiology proposed by Picton and Hillyard (1974).

Adult↗
PubMed1984

Self-injurious behavior and stereotypy in an institutionalized mentally retarded population.

Demographic variables and behavioral characteristics of institutionalized mentally retarded clients exhibiting both self-injurious behavior (SIB) and stereotypy, stereotypy alone, SIB alone, or neither of these behaviors were analyzed. Overall, there were no significant differences for the demographic variables measured. Multivariate analyses revealed that severity and frequency of behavior, sensory handicap, and sex of the subject were the best predictors of group membership. Moreover, this research suggests that SIB and stereotypy can be classified as stereotyped SIB and withdrawal stereotypy, respectively. Thus, the treatment modalities presently being applied to these behaviors could be inappropriate. Additional evidence is discussed that supports the belief that an organic physiological substrate or mechanism could be related to these aberrant behavior patterns, which would necessitate a new diagnostic classification and alternative forms of treatment.

Adolescent↗
PubMed1983

Naloxone attenuates self-abusive behavior in developmentally disabled clients.

The opiate antagonist naloxone was effective in reducing self-abusive behavior in two mentally retarded clients with an extensive history of such behavior. Three doses of naloxone (0.1, 0.2, 0.4 mg) were compared with a vehicle solution in a double-blind, crossover design. Naloxone greatly attenuated self-abusive episodes in one client and eliminated them entirely in the second client. In addition, use of self-restraining behavior by one client was reduced. The findings suggested that some clients with self-injurious behavior may have disturbances of the endogenous opiate system. Maintenance of self-abuse by tonically elevated pain threshold and/or by the putative addictive characteristics of such behavior was discussed.

Adult↗
PubMed1983

Relationship of sedative-hypnotic response to self-injurious behavior and stereotypy by mentally retarded clients.

Groups of clients exhibiting both self-injurious behavior (SIB) and stereotypy, stereotypy alone, SIB alone, or neither of these types of behavior were rated in terms of response to sedative-hypnotic medication. Sixty-eight percent of the clients with both SIB and stereotypy maintained wakefulness and were either resistive, combative, restless, uncooperative, or abusive after treatment with sedative-hypnotics. Thirty-nine percent of the clients with only SIB and 35 percent of the clients with only stereotypy evidenced such "paradoxical" responses to these medications. None of the matched control clients displayed paradoxical responses. This result suggests that an impaired endogenous opiate system characterized by increased levels of beta-endorphin may mediate and maintain a type of syndrome of SIB that involves the presence of stereotypy, implying the need for a new diagnostic classification and treatment of these aberrant behavioral disorders.

Adolescent↗
PubMed1983

Methylphenidate hydrochloride given with or before breakfast: I. Behavioral, cognitive, and electrophysiologic effects.

Methylphenidate HCl (Ritalin) is usually given for the treatment of hyperactivity or attention deficit disorder (ADD) at 30 minutes to one hour before meals. This schedule is based on the assumption that, when taken with meals, its absorption or metabolism is altered. However, no behavioral or pharmacologic data exist to support this recommendation. Eleven patients with attention deficit disorder were tested to evaluate this hypothesis using a double-blind crossover design (methylphenidate with or before breakfast) with a placebo control condition. Parents' ratings, performance on a paired-associate learning test, and cortical auditory-evoked potentials were measured. All of these measurements showed clear differences between the placebo condition and conditions when medication was given. However, none of the measurements showed a significant difference between the conditions when methylphenidate was given with breakfast and the condition when methylphenidate was given 30 minutes before breakfast.

Analysis of Variance↗
PubMed1982

Trial of an ACTH4-9 Analogue (ORG 2766) in children with intractable seizures.

The ACTH4-9 Analogue (ORG 2766) is an orally administered neuropeptide which has been showed to have behavioral effects in human subjects, but does not have any steroidogenic effects, nor other significant side effects. This study was a double-blind, crossover trial of the ACTH4-9 analogue in four children with intractable seizures. There was some slight improvement in seizure frequency in two patients, with an equivocal improvement in a third child. A fourth child was unchanged, while the fifth dropped out of the study. There were no side effects from the therapy. This questionable improvement in seizure frequency in some of the most intractable patients with seizure disorders indicates the need to further assess this ACTH4-9 analogue in a larger study over a longer period of time.

Adrenocorticotropic Hormone↗
PubMed1981

Induction of analgesia by central administration of ORG 2766, an analog of ACTH4--9.

Dose-dependent analgesia was produced by microinjection of ORG 2766 into the periaqueductal gray (PAG). This analgesia was found to be potent and long-lasting and occurred at doses which were equimolar to those necessary for morphine analgesia. The same doses failed to produce analgesia by the cerebroventricular route, suggesting that the PAG was the site of action of this effect. Naloxone failed to reduce the analgesia and morphine tolerant did not diminish the effect significantly. Additionally, ORG 2766 at concentrations up to 10 micrometer failed to inhibit binding of [3H]naloxone to brain opiate receptors in vitro. These results suggest a non-opiate mechanism of action and are discussed in terms of a proposed alpha-MSH or ACTH receptor.

Adrenocorticotropic Hormone↗
PubMed1981

Effects of alpha-MSH and beta-endorphin on startle reflex in rat.

Twelve rats received peripheral injections (20 micrograms/rat) of alpha-MSH, beta-endorphin or the vehicle solution and were subsequently tested for the motor and cardiac responses to repeated presentations of intense acoustic stimuli. Each subject received all treatments in a counterbalanced order with 3-day periods between each session. beta-Endorphin tended to decrease the amplitude of the habituated motor startle reflex, while alpha-MSH produced a slight increase in basal heart rate during the habituation session. Neither peptide had any effect on the cardiac response to intense acoustic stimulation. The effects of the two peptides were not directly antagonistic but they are consistent with the hypothesis that complex attentional processes were facilitated by MSH/ACTH fragments and inhibited by the endorphins.

Animals↗
PubMed1981

Effects of melatonin on startle reflex in rat.

In two experiments the effects of melatonin were investigated on the motor, cardiac and emotional components of the startle reflex induced by an intense acoustic stimulus. Melatonin inhibited the motor movements and significantly decreased the HR responses of rats pretested with these procedures. Melatonin decreased the HR responses to stimulation whereas the HR responses of the rats treated with the vehicle solution increased. Melatonin treatment also inhibited the startle-induced defecation compared with the vehicle injection. These findings suggest that melatonin exerts inhibitory effects on the CNS, on sensory reflex and on stress responses.

Acoustic Stimulation↗
PubMed1981

Brain beta-endorphin-like immunoreactivity in adult rats given beta-endorphin neonatally.

beta-endorphin-like immunoreactivity was measured by radioimmunoassay in the brains of adult rats treated neonatally with beta-endorphin, naloxone, or vehicle. After treatment with beta-endorphin, the decreases observed in beta-endorphin-like immunoreactivity in the hypothalamus, pineal, midbrain, pons-medulla, hippocampus, striatum, frontal cortex, occipital cortex, and posterior cortex were highly significant but the 23% decrease in the thalamus was not significantly different from that of control rats. Neonatal administration of naloxone only resulted in a significant decrease in beta-endorphin-like immunoreactivity in the hypothalamus. In contrast, no differences were discernible in content of either beta-endorphin-like immunoreactivity or ACTH-like immunoreactivity in the pituitary of rats treated with beta-endorphin, naloxone, or vehicle in the neonatal period. These same rats had shown an increased threshold to painful thermal stimulation by the tail-flick test after administration of either beta-endorphin or naloxone at birth. The results suggest that neonatally injected beta-endorphin may alter the levels of beta-endorphin-like immunoreactivity in rat brain as well as the response to pain.

Animals↗
PubMed1981

Intraventricular administration of MSH induces hyperalgesia in rats.

In a completely crossed, double blind designed study, six rats received intraventricular injections of 0.1, 1.0 and 10 micrograms of alpha-MSH and a placebo. The rats were tested for response to painful thermal stimuli with the tail-flick test. All of the doses of alpha-MSH produced hyperalgesia during the first 20 min of testing. Only the 1.0 microgram dose of alpha-MSH produced hyperalgesia throughout the 80 min course of the experiment. This study, coupled with previous reports that MSH/ACTH fragments may attenuate morphine-induced analgesia, suggest that MSH can have opposite actions from those of the endorphins. It is possible that alpha-MSH and related peptides may be endogenous anti-opiates.

Animals↗
PubMed1980

Are learning and attention related to the sequence of amino acids in ACTH/MSH peptides?

Learning and attention were examined in rats after injections of one of several molecules related to adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH). The initial phase of the learning process was linearly related to the length of the peptide with the smallest fragment (MSH/ACTH 4-10) improving learning the most and the largest molecule (ACTH 1-24) exerting no effect. Later stages of the learning problem, which were sensitive to the attentional state of the organism, resulted in U-shaped relations with the length of the same peptides. Enhancement of attention was significant only for the MSH compounds. These data indicate that some behaviors may be influenced as a function of the redundant information contained in the molecule while other behaviors may be discretely related to the specific conformation of the molecule.

Adrenocorticotropic Hormone↗