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Biomedical subjects

D Hommer

Publications and source records attributed to D Hommer.

34 records · Page 2Linked to original sources
PubMed1994

Impairments in reflective cognitive functions in alcoholics: a neuropharmacological model.

The ability to make use of reflective cognitive operations in monitoring and evaluating remembered events is impaired in subgroups of nominally cognitively unimpaired, detoxified alcoholics. Alcoholics, relative to controls, make more errors in identifying the source of remembered information (i.e. whether a remembered word was self-generated or was a stimulus word presented by the experimenter), and are impaired in their ability to inhibit confabulatory errors (intrusions). The cognitive-memory impairment expressed in benzodiazepine-treated normal volunteers mimics this impairment in alcoholics. Disturbances in prefrontal and frontal lobe functions may be involved in this selective impairment in cognition in many alcoholics and may also contribute to what accounts for the failures in reflective cognitive operations observed in amnestic patients.

Alcoholism↗
PubMed1993

Dissociation of benzodiazepine-induced amnesia from sedation by flumazenil pretreatment.

The human amnestic syndrome associated with lesions of the hippocampus and amygdala is characterized by a selective impairment of recent (explicit, episodic) memory. Benzodiazepine (BZ) treated normal subjects demonstrate similar, marked impairments in episodic memory, but in addition, BZ also induces sedation and inattention. Thus, the amnestic effects of BZ may be secondary to drug-induced sedation. However, when subjects were pretreated with the specific BZ receptor antagonist, flumazenil, the sedative and attentional effects of diazepam were blocked, but a marked impairment in episodic memory still occurred. This demonstrates that, using neuropharmacological methods, it is possible to produce a dissociation of memory impairment from inattention and sedation. Such distinct patterns of cognitive dysfunction may serve as models for clinical cognitive syndromes.

Adult↗
PubMed1993

Benzodiazepine pharmacodynamics: utility of eye movement measures.

The utility of several measures of saccadic and smooth pursuit eye movements as benzodiazepine pharmacodynamic measures was explored in 24 psychiatrically and medically health control subjects. Measures of sedation and memory impairment were also included. Subjects received four logarithmically increasing doses of intravenous diazepam at 15-min intervals on 1 day resulting in monotonically increasing plasma diazepam levels, and placebo on another day in random order 1 week apart. Measures were collected twice at baseline, once after each dose of diazepam/placebo and twice more, 15 and 30 min after the last dose. Peak saccadic velocity and smooth pursuit gain showed the greatest overall and dose-dependent drug effect among eye movement measures. Although effect sizes at the highest dose for memory impairment and self-rated sedation were comparable to these two measures, reliability (i.e., placebo-day fluctuation) with these measures was considerably poorer. Log-linear pharmacodynamic modeling was used to calculate the effective dose (ED30) or concentration (EC30) required to reduce saccadic velocity or pursuit gain by 30%. Almost all (23/24) subjects had linear and easily interpretable plots for saccadic velocity, while a majority (19/24) of subjects had interpretable plots for smooth pursuit gain. The distribution of ED30 and EC30 values showed a wide range of sensitivities to diazepam. These findings suggest that saccadic velocity and smooth pursuit gain are sensitive, reliable, quantitative benzodiazepine pharmacodynamic measures.

Adolescent↗
PubMed1992

Selective effects of triazolam on memory.

The effects of benzodiazepine (triazolam 0.25 and 0.50 mg) on different aspects of cognitive function were assessed. Triazolam impaired free recall and recognition of information presented after drug administration. In contrast to these impairments in explicit memory, a memory function that did not require conscious awareness was not altered by triazolam. Similarly, triazolam did not affect subjects' abilities to access semantic memory.

Adult↗
PubMed1992

Effect of acute and chronic benzodiazepines on plasma GABA in anxious patients and controls.

The acute effects of diazepam on plasma GABA were determined in 18 patients with panic disorder, 13 patients with generalized anxiety disorder and 20 healthy controls. All subjects were benzodiazepine-naive. Four logarithmically increasing doses of diazepam/placebo were administered intravenously at 15-min intervals on 2 separate days. Plasma GABA was measured at baseline and 3 min after the highest dose of diazepam/placebo. There was an overall decrease in plasma GABA that was significantly greater following diazepam compared with placebo, but no group differences in response. In a separate group of 18 panic disorder patients receiving chronic benzodiazepine treatment with alprazolam, the same diazepam infusion procedure (no placebo day) produced decreases in plasma GABA similar to those seen in the untreated panic disorder patients. The clinical and physiologic implications of these findings are discussed.

Adult↗
PubMed1991

Neuroendocrine effects of diazepam in panic and generalized anxiety disorders.

The adrenocorticotropic hormone (ACTH), cortisol, and growth hormone responses to four consecutive, logarithmically increasing doses of intravenous diazepam compared with placebo given at 15-min intervals were examined in patients with panic disorder (n = 13), generalized anxiety disorder (n = 8), and healthy controls (n = 13). Diazepam caused dose-dependent decreases in cortisol and increases in GH and dose-independent decreases in ACTH. There were no patient-control differences, possibly due to either the small sample size of the experimental paradigm, which tested subjects in an upright, sitting position in mildly arousing circumstances.

Adrenocorticotropic Hormone↗
PubMed1990

Effects of the acute administration of caffeine in patients with schizophrenia.

Caffeine, 10 mg/kg, was administered to 13 schizophrenic patients in a double-blind placebo-controlled study of its behavioral effects. Some measures of psychopathology were significantly increased: Brief Psychiatric Rating Scale (BPRS) total, BPRS subscales thought disorder, unusual thought content, and euphoria-activation, and several individual BPRS items. Nurses' Bunney-Hamberg ratings of psychosis and mania, comparing the day before with the day after pharmacological challenge, increased significantly. Compared to placebo, caffeine also produced significant increases of diastolic blood pressure and cortisol. Thus, these findings indicate that caffeine increases arousal and has a psychotogenic effect when administered to schizophrenic patients. The possible roles of various neurotransmitters is discussed with special emphasis on caffeine's actions on dopaminergic and adenosinergic systems.

Adolescent↗
PubMed1990

Reduced benzodiazepine sensitivity in panic disorder.

We evaluated the functional sensitivity of the gamma-aminobutyric acid-benzodiazepine supramolecular complex in 9 patients with panic disorder and 10 psychiatrically healthy control subjects by comparing the effects of four logarithmically increasing doses of intravenous diazepam on saccadic eye movement velocity, memory, and self-rated sedation. Patients with panic disorder were less sensitive than controls to diazepam using eye velocity as the dependent measure. Sedation and memory effects did not distinguish the two groups. These findings suggest that panic disorder is associated with functional subsensitivity of the gamma-aminobutyric acid-benzodiazepine supramolecular complex in brain-stem areas controlling saccadic eye movements.

Adult↗
PubMed1988

Benzodiazepine withdrawal: overview and implications for the treatment of anxiety.

The authors critically review 20 reports (studies and large case series) detailing the nature, severity, and variability of benzodiazepine withdrawal syndromes. Factors affecting the frequency and intensity of withdrawal are identified, and methodologic problems limiting the generalizability of certain findings are pointed out. Treatment approaches for minimizing withdrawal are reviewed, and implications for the problem of long-term benzodiazepine use and dependence are discussed.

Anti-Anxiety Agents↗
PubMed1985

Pharmacological and neurochemical properties of 1,4-diazepines with two annelated heterocycles ('hetrazepines').

1,4-Diazepines with two annelated heterocycles ('hetrazepines') such as brotizolam (WE 941), WE 973 and WE 1008 bind with high affinities to benzodiazepine receptors in the central nervous system. Brotizolam has a pharmacologic spectrum of action similar to clinically useful benzodiazepines, while the closely related derivatives WE 973 and WE 1008 appear to lack hypnotic action. Unlike other benzodiazepine receptor ligands which share common pharmacologic properties with the benzodiazepines, the apparent affinities of WE 973 and WE 1008 are not increased significantly in the presence of GABA, even at an elevated incubation temperature. Furthermore, the apparent affinities of these compounds do not appear to be reduced as a result of increasing the incubation temperature. Brotizolam, like the benzodiazepines, facilitates GABAergic transmission in zona recitulata neurons of the substantia nigra. In contrast, at a dose which inhibits cell firing, WE 973 does not appear to significantly augment the inhibitory action of GABA in these cells. These observations suggest that the so-called 'GABA shift' may not be a valid means of distinguishing benzodiazepine-like compounds in vitro. Furthermore, these data suggest that facilitation of GABAergic transmission may be necessary for the hypnotic action of benzodiazepine receptor ligands, but not for the anticonflict or the anticonvulsant actions of such compounds.

Action Potentials↗
PubMed1985

Atrophy limited to the third ventricle in chronic schizophrenic patients. Report of a controlled series.

Computed tomographic scans of 30 chronic schizophrenic patients and 26 matched medical controls were blindly assessed for ventricular brain ratio, cortical atrophy, third-ventricle diameter, and cerebellar atrophy. Schizophrenic patients had significantly larger third ventricles than the medical controls. There was no difference in the other brain morphologic variables. Phenomenology, drug response, CSF levels of 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and a wide variety of clinical variables did not correlate with any measure of brain morphology. Clinicopathologic correlates of brain morphology may be limited to those patients with significant atrophy.

Adult↗
PubMed1984

Neuroleptic-induced decrease in plasma homovanillic acid and antipsychotic activity in schizophrenic patients.

Plasma-free homovanillic acid, a major metabolite of dopamine, was measured in chronically ill schizophrenic patients both before and during treatment with the antipsychotic phenothiazine, fluphenazine. Neuroleptic treatment was associated with a significant time-dependent decrease in plasma homovanillic acid from pretreatment values, which were significantly elevated when compared with those of age- and sex-matched healthy control subjects. Further, both the absolute concentrations as well as the neuroleptic-induced reductions in plasma homovanillic acid determined over 5 weeks of neuroleptic treatment were statistically significantly correlated with ratings of psychosis and improvement in psychosis, respectively. These findings suggest that the delayed effects of neuroleptic agents on presynaptic dopamine activity may more closely parallel their therapeutic actions than do their immediate effects in blocking postsynaptic dopamine receptors and that a decrease in dopamine "turnover" may be responsible for their antipsychotic effects.

Adult↗
PubMed1984

Electrophysiological and pharmacological actions of the convulsant benzodiazepine Ro 5-4864.

Ro 5-4864 (4'-chlorodiazepam) elicited convulsions in mice with a CD50 of 23.5 mg/kg (i.p.) and increased the firing rate of substantia nigra zona reticulata neurons in a dose dependent fashion (0.5-4 mg/kg i.v.). Diazepam and clonazepam, but not Ro 15-1788, were potent inhibitors of Ro 5-4864 induced convulsions. Ro 15-1788 was also ineffective in reversing Ro 5-4864 induced increases in cell firing of zone reticulata neurons. Muscimol potently inhibited the seizures and reversed increases in cell firing elicited by Ro 5-4864. Phenobarbital and pentobarbital inhibited Ro 5-4864 induced convulsions with moderate potencies, while phenytoin and carbamazepine were ineffective at doses of up to 100 mg/kg. These observations suggest that Ro 5-4864 does not elicit its pharmacologic actions through a direct action at a 'brain-type' benzodiazepine receptor. However, both the profile and potency of compounds effective in inhibiting the electrophysiological and pharmacological effects of Ro 5-4864 suggest that this compound may act by perturbation of a component of the GABA-benzodiazepine receptor chloride ionophore complex. These findings do not, however, rule out a direct involvement of the high affinity 'peripheral-type' benzodiazepine receptors found in brain.

Animals↗
PubMedDate not supplied

Eye movement task related to frontal lobe functioning in children with attention deficit disorder.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) has been postulated to be related to dysfunction of the prefrontal cortex. In the oculomotor delayed response task, a subject is cued as to where he or she should look (shift visual gaze to) but must delay a short period and then shift gaze to the location where the cue previously existed but no longer exists (a memory-guided saccade). Dependent measures from this task provide information on three functions tentatively tied to prefrontal cortex functioning: the ability to inhibit response (during the delay period), preparation of motor response (inversely tied to the latency of shifting visual gaze), and accuracy of working visuospatial memory (accuracy of the memory-guided saccade). METHOD: Thirteen children with ADHD and 10 normal controls, aged 9 to 12 years, were tested using an 800-msec delay period. RESULTS: Children with ADHD showed, relative to normal controls, deficits on inhibiting response during the delay period but no differences in latency (preparation of motor response) or accuracy of visuospatial memory. CONCLUSIONS: These results support the hypothesis that the primary deficit in ADHD is difficulty in inhibition of response. This deficit may be associated with pathology located outside the dorsolateral prefrontal cortex.

Adolescent↗
PubMedDate not supplied

The effect of corticosteroids in the treatment of experimental sinusitis.

Emerging evidence indicates that medically recalcitrant sinusitis may be associated with a prolonged and excessive state of inflammation rather than a simple bacterial infection. Corticosteroids have been anecdotally reported to be helpful in treating patients with sinusitis; however, there are no scientific studies documenting the safety and efficacy of corticosteroid therapy in sinusitis. To resolve the controversy over whether corticosteroids promote or inhibit the resolution of sinusitis, we present a prospective study of 80 rabbits with surgically introduced pseudomonal sinusitis that were then treated in one of four arms: control, ceftazidime, methylprednisolone, and ceftazidime with methylprednisolone. Sinus cavities were then evaluated after 5, 14, 21, and 28 days of treatment both by histologic inflammation grading and bacterial quantification. Results showed a significant decrease in bacterial loads in both the antibiotic and antibiotic with steroid arms over control animals, although no difference was seen between the two. Histologic grading showed a similar trend, although statistical significance was not obtained. Overall, this study demonstrated no clear advantage of steroids in the treatment of sinus infections using this model. At the same point, no significant reduction in the effectiveness of antibiotic therapy was seen with concurrent steroid use. A number of limitations of the animal model are noted and the need for human studies in this area is discussed.

Animals↗