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Biomedical subjects

M W Dysken

Publications and source records attributed to M W Dysken.

At least 19 recordsLinked to original sources

Measuring delirium severity in older general hospital inpatients without dementia. The Delirium Severity Scale.

The authors evaluated the validity, reliability, and sensitivity to change of the Delirium Severity Scale (DSS), a 10-minute assessment consisting of Forward Digit Span and Similarities. Twenty-two older inpatients with delirium but not dementia and 15 control patients were administered the DSS during hospitalization. Scores were significantly inversely correlated with experts' quantitative ratings of severity at all three time-points examined. The DSS showed significant improvement over time (P < 0.001) and significant correlation with improvement in expert ratings (P = 0.026). The DSS shows promise as a valid and reliable measure sensitive to changing symptom severity.

Age Factors

Phenomenological and pharmacological study of provoked obsessive/anxiety symptoms in obsessive-compulsive disorder: a preliminary study.

BACKGROUND: Inclusion of obsessive-compulsive disorder (OCD) as an anxiety disorder in DSM-i.v. assumes that anxiety is the primary symptom of OCD; however, persuasive empirical evidence in support of this view has not been presented yet. In the present study we hypothesized that provoked anxiety symptoms respond better to intravenous diazepam than would provoked obsessions. We, therefore, reasoned that anxiety symptoms are secondary symptoms of OCD. METHODS: To test the hypothesis we designed a double-blind, randomized, placebo-controlled crossover study. Patients underwent four experimental conditions in which the sequence of symptom provocation and i.v. injection of (placebo or diazepam) were alternated. Baseline and i.v. injection-induced symptom changes were assessed using visual analogs. RESULTS: Obsessions and anxiety correlated strongly for all four experimental conditions in which the sequence of the symptom provocation and diazepam i.v. injections was alternated. i.v. diazepam injection before and after symptom provocation failed to preferentially modulate anxiety symptoms over obsessions. Unexpectedly, in the group in which i.v. diazepam injection preceded the symptom provocation, reduction of mean obsessions was even more pronounced. CONCLUSIONS: Strong correlations between anxiety and obsessions at baseline, during symptom provocation, and after i.v. diazepam infusion suggest that anxiety and obsessions are tightly coupled phenomena in OCD.

Adult

Determination of trazodone and its metabolite, 1-m-chlorophenyl-piperazine, in human plasma and red blood cell samples by HPLC.

OBJECTIVES: To develop an HPLC method for the analysis of trazodone and its metabolite, 1-m-chlorophenyl-piperazine (m-CPP), in human plasma and red blood cells. DESIGN AND METHODS: The analytes were extracted by heptane containing 1.5% isoamyl alcohol, back extracted into phosphoric acid and analyzed by reverse phase HPLC with UV detection. RESULTS: In seven randomly selected, male, human subjects plasma concentrations (nmol/l) were 380-5841 for trazodone and 14-237 for m-CPP while those in packed red blood cells were 98-634 for trazodone and 15-155 for m-CPP. Plasma trazodone concentrations were 4-11-fold higher than those in red blood cells while those of m-CPP were about equal. This may be the first report on concentrations of trazodone and m-CPP in human red blood cells. CONCLUSIONS: This sensitive method can be used for monitoring trazodone and m-CPP in human plasma and red blood cells.

Adult

Serum anticholinergic activity in hospitalized older persons with delirium: a preliminary study.

OBJECTIVE: To evaluate the relationship between total serum anticholinergic activity (SAA) and the presence or absence of delirium in older hospitalized persons on general medical wards. DESIGN: Case-control study and within-subjects repeated-measures in recovered delirious patients. SETTING: Minneapolis Veterans Affairs Medical Center medical wards. PARTICIPANTS: Eleven male delirious patients (DSM-III-R criteria) aged 60 or older and 11 comparably aged male nondelirious controls. MEASUREMENTS: Radioreceptor bioassay of total SAA using tritiated quinuclidinyl benzilate (QNB) binding to muscarinic receptors. Results are expressed in terms of atropine equivalents (nM). MAIN RESULTS: Mean SAA was significantly elevated in the delirious group (mean +/- SD = 6.05 +/- 2.97 nM atropine equivalents) compared with the controls (3.38 +/- 2.49; t(20) = 2.28, P < .05). At study entry, mean SAA was significantly higher in delirious subjects whose symptoms eventually resolved completely (mean +/- SD = 7.77 +/- 2.37) compared with subjects whose delirious symptoms persisted (3.99 +/- 2.30; t(9) = 2.68, P < .05). All six patients in whom delirium resolved completely had a decrease in serum anticholinergic activity when measured during delirium (7.77 +/- 2.37) and after symptom resolution (3.92 +/- 2.61; t(5) = 3.29, P < .05). CONCLUSIONS: Our findings suggest that serum anticholinergic activity may play a role in delirium in medical inpatients. The relationships between SAA and delirium in medical patients and between total SAA and medication use warrant further study.

Aged

A review of GHRH stimulation test in psychiatry.

We critically reviewed controlled investigations of the growth hormone releasing hormone (GHRH) stimulation test in depression, anorexia nervosa, bulimia, panic disorder, schizophrenia, and Alzheimer's disease. Comparisons of GH responsiveness between patients and controls within each diagnostic category were equivocal and in some cases contradictory. Factors that may contribute substantially to the inconsistent findings within diagnostic categories include (1) the variability of GHRH-simulated GH among control groups; (2) the lack of uniformity in test procedures and outcome measures; and (3) the age and gender of subjects. In addition, the individual reproducibility of the GHRH stimulation test has not been adequately investigated and until the test's stability within subjects can be determined, the validity of interpretations resulting from the GHRH simulation test are in question.

Alzheimer Disease

The Yale-Brown Obsessive-Compulsive Scale: measures of internal consistency.

We examined the construction of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and performance of subscale items based on data from 204 patients with obsessive-compulsive disorder (OCD) who participated in a multicenter drug treatment study. Factor analysis was used to examine the relationship among the 10 items that make up the Y-BOCS instrument. Models were computed in which both two- and three-factor solutions were estimated. Within the two-factor solution analyses, the factor distribution was not so consistent as in the three-factor solution analyses, and a shift in the factor distribution was noted after treatment. In the three-factor solution analyses, an independent resistance construct emerged in addition to the obsessive and compulsive constructs. Examination of the postreatment factor scores showed that the Y-BOCS resistance items did not assess OCD symptom change as sensitively as the rest of the Y-BOCS items did.

Adult

Blunting of the neurotensin mRNA response to haloperidol in the striatum of aging rats: possible relationship to decline in dopamine D2 receptor expression.

Neuroleptic drugs such as haloperidol (H) induce a rapid increase in neurotensin/neuromedin N (NT/N) gene expression in the dorsolateral striatum (DLSt) and nucleus accumbens (NA) in young adult rats. This effect may be mediated by post-receptor effectors that are activated by dopamine D2 receptor antagonism. The regional pattern of induction of neurotensin gene expression correlates with the side effect profile of particular neuroleptics. As motor side effects of H differ in aged animals, we hypothesized that the regional expression of the neurotensin gene may differ between young and old animals. We administered H or saline acutely to 3, 14, and 25 month-old Fischer 344 rats, followed by in situ hybridization and quantitative autoradiography for NT/N mRNA. There was a significant age effect on the H-induced NT/N mRNA response in the DLSt, but not the NA, of older animals. In addition to the blunted NT/N mRNA response, significant decreases in D2 receptor mRNA were observed in the lateral striatum of another group of young, middle-aged, and aged rats. Age-related blunting of the NT/N mRNA response to H in the DLSt may be due in part to a decrease in D2 receptors in this structure.

Aging

Quantitative EEG in obsessive-compulsive disorder.

Electroencephalograms (EEGs) were recorded from 13 unmedicated and nondepressed patients with DSM-III-R obsessive-compulsive disorder (OCD) and from 10 age-matched controls. All subjects were also administered the Wechsler Memory Scale Delayed Logical Memory and Delayed Visual Reproduction tests. Quantitative analysis of the EEG revealed lower log absolute power in the delta, beta 1, and beta 2 bandwidths for OCD patients at frontal and right-hemisphere locations. OCD patients displayed greater hemispheric asymmetries in EEG activity based on difference measures of EEG power from homologous electrode pairs, indicative of severe right hemisphere EEG hypoactivity. Standardized measures of hemispheric asymmetry for the beta 2 bandwidth accurately predicted group membership and were correlated both with poorer patient performance on the visual-spatial memory task and better performance on the verbal memory task. OCD patients were significantly impaired on the visual-spatial task, but not on the verbal memory test, relative to controls.

Adult

Resolution of the interference from carbamazepine and diphenhydramine during reversed-phase liquid chromatographic determination of haloperidol and reduced haloperidol.

Carbamazepine and diphenhydramine interfered with the assays of haloperidol and its metabolite, reduced haloperidol, by reversed-phase HPLC. Retention times of haloperidol, reduced haloperidol, and the interfering drugs were very sensitive to the percentage of potassium phosphate buffer in the mobile phase as well as to the final pH of the eluant. Retention times were not very dependent upon ionic strength of the eluting solvent mixture. Haloperidol and reduced haloperidol in the range of 0.5-10 ng/mL were analyzed in the presence of 0.2 micrograms/mL diphenhydramine and 5 micrograms/mL of carbamazepine. The concentrations of all drugs used were in their expected therapeutic ranges. The isocratic chromatographic conditions were as follows: 25-cm x 4.6-mm C-18 column; mobile phase, 75% phosphate buffer (final concentration, 0.06M) and 25% acetonitrile; final pH, 3.5; flow rate, 2.5 mL/min; and detection by UV absorption at 220 nm. Additional changes in the percent buffer in the mobile phase may be useful in achieving separation of other interfering compounds.

Buffers

Neuropsychological performance in obsessive-compulsive disorder.

Neuropsychological functioning was examined in a group of 18 nondepressed patients with obsessive-compulsive disorder (OCD) and 18 age-, education-, and gender-matched normal controls. A recent nonverbal memory deficit was identified in the patients with OCD. From performance on timed and untimed measures of the same constructs, it appears that OCD patients score more poorly than controls when speed is a factor. Although performance on a timed tactual-spatial motor test was also impaired, it is unclear whether this deficit is attributable to the nonverbal memory and/or speed deficits. Deficits in verbal abilities, including recent verbal memory, were not identified. Results were equivocal for executive function and visual-spatial abilities. The previously established association of recent nonverbal memory abilities with functioning of the right mesial temporal area is discussed in the context of current hypotheses about the neuroanatomic substrate of OCD.

Adult

Distribution of peripheral lymphocytes in Alzheimer patients and controls.

Deficient immunoregulation has been postulated to play a role in the pathogenesis of Alzheimer's dementia. Recently, lymphopenia was reported to be more prevalent in Alzheimer patients than in control subjects. In addition, a decreasing number of total lymphocytes was found to be significantly correlated with increasing severity of dementia. In an attempt to replicate these findings, we studied 55 Alzheimer patients and 41 healthy controls of comparable age and gender, but found no significant difference in the distribution of total lymphocytes between these groups. Furthermore, total lymphocytes were not significantly correlated with dementia severity. Our findings, therefore, do not lend further support to an immune hypothesis for Alzheimer's dementia.

Adult

The Symptom Checklist-90: Obsessive-Compulsive Subscale: A reliability and validity study.

Twenty-three nondepressed patients with DSM-III obsessive-compulsive disorder completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Symptom Checklist-90 (SCL-90), and the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH-GOCS) once a week for a total of three times during a 2-week medication-free period and 10 times during a 10-week double-blind drug treatment period. The pretreatment test-retest reliabilities were determined for the Y-BOCS, NIMH-GOCS, and the SCL-90-Obsessive-Compulsive Subscale (SCL-90-OCS). Comparisons of the three instruments revealed that the Y-BOCS and the NIMH-GOCS were significantly more reliable than the SCL-90-OCS. Posttreatment correlations were obtained between change scores on the Y-BOCS and NIMH-GOCS and the SCL-90-OCS. Correlations were high and statistically significant for both the Y-BOCS and the NIMH-GOCS, but the correlations of the SCL-90-OCS with the Y-BOCS, NIMH-GOCS, Physician's Global Rating, and the Patient's Global Rating were poor. The findings suggest that the SCL-90-OCS may not be a sensitive instrument in assessing change in obsessive-compulsive symptoms.

Adult

Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type.

OBJECTIVE: Milacemide, a MAO-B inhibitor that is also a prodrug for glycine, was tested as a treatment for senile dementia of the Alzheimer type (SDAT) because of its potential for enhancing cognition in animal models of impaired learning and memory. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Sixteen study sites, both university-affiliated and private. PATIENTS: A total of 228 outpatients (116 men and 112 women) with SDAT, ranging in age from 49-93 years. INTERVENTION: 1200 mg/day milacemide treatment for 1 month (113 patients received milacemide, and 115 patients received placebo). MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale and the Mini-Mental State Examination. RESULTS: Milacemide-treated SDAT patients did not show significant improvement in any of the outcome measures used. Significant elevations in liver enzymes in four subjects were of sufficient magnitude to necessitate withdrawal from the study. CONCLUSIONS: Milacemide does not appear to be an effective treatment in enhancing cognition in SDAT patients.

Acetamides

Haloperidol decanoate pharmacokinetics in red blood cells and plasma.

Red blood cell (RBC) and plasma concentrations of haloperidol (H) and reduced haloperidol (RH) were determined in nine patients (five men, four women) who had been receiving monthly injections of haloperidol decanoate (HD) for at least 3 months. A very sensitive high performance liquid chromatography method was used to measure H and RH, which could be detected at levels as low as 0.1 ng/ml. Blood samples for H and RH were drawn at the end of weeks 1, 2, 3, and 4 of a 4-week cycle. Monthly HD dosages ranged from 50 mg to 200 mg. At each time point RBC H did not differ significantly from plasma H. RBC RH and plasma RH did not change significantly over time and were consistently lower than RBC H and plasma H. However, RBC RH levels were higher than plasma RH levels. Also, the ratios of RBC RH/H were higher than were the ratios of plasma RH/H, which reflect an accumulation of RH intracellularly. HD dosage was highly correlated with both RBC H and plasma H, but RBC RH and plasma RH were not significantly related to dosage at any time point. Significant correlations were observed between HD dosage and prolactin concentration at week 1 and between prolactin concentration and RBC H and plasma H at weeks 1 and 4. Blood concentrations of H and RH and the corresponding standardized areas under the curve were not significantly related to smoking.

Adult

Haloperidol and reduced haloperidol in saliva and blood.

A total of 18 outpatients (17 male, 1 female) ranging in age from 36-66 years old were on a constant dosage of haloperidol in equally divided doses at 9:00 a.m. and 9:00 p.m. for at least 1 month. DSM-III-R diagnoses included schizophrenia (N = 9), schizoaffective disorder (N = 3), bipolar disorder (N = 4), organic mental disorder (N = 1), and delusional disorder (N = 1). Blood samples for steady-state concentrations of plasma and red blood cell haloperidol (H) and reduced haloperidol (RH) were drawn at 9:00 a.m. (12 hr trough). The haloperidol dosage was held at 9:00 a.m. until samples of whole saliva and parotid saliva could be collected for flow rates and concentrations of H and RH. Haloperidol dosages ranged from 1 mg/day to 60 mg/day (mean 11 +/- 15). Correlation coefficients were calculated for saliva concentrations versus blood levels and for saliva secretion rates versus blood levels. The correlations between whole saliva measures and blood concentrations were all higher than the correlations between parotid saliva measures and blood concentrations. In one case the higher correlation reached statistical significance. There was only one case in which substitution of saliva secretion rate improved the correlation between measures with saliva concentration. Our findings suggest that saliva measures of H and RH are useful alternatives to plasma concentrations in monitoring maintenance haloperidol treatment.

Adult

Platelet 3H-imipramine binding sites in obsessive-compulsive behavior.

Several studies indicate a serotonergic dysfunction in patients with obsessive-compulsive disorder (OCD). We examined serotonergic function in OCD by determining platelet 3H-impiramine binding sites in patients with OCD during a drug-free baseline period as well as normal control volunteers. The maximum number of binding sites (Bmax) and apparent dissociation constant (Kd) was determined using 3H-imipramine (IMI) as the binding ligand. We observed that the mean 3H-IMI binding Bmax (fmol/mg protein) determined in 24 patients with OCD was not significantly different from that in 23 normal control subjects. There were no significant differences in the Kd between patients with OCD and normal control subjects. Our results are thus similar to those reported by Insel et al (1985) and Black et al (1990), who observed no significant differences in platelet 3H-IMI binding between OCD patients and controls; but different from those reported by Weizmann et al (1986), who observed decreased 3H-IMI Bmax in OCD patients. The discrepancy in the results is not clear, but may be related to several factors. Our results thus indicate that any abnormality in serotonergic function present in patients with OCD is not related to imipramine binding sites in the platelets. However, the possibility that there may be an abnormal platelet serotonin uptake or other serotonergic function in OCD cannot be ruled out.

Adult

A review of disorders of water homeostasis in psychiatric patients.

Disorders of water homeostasis are common in psychiatric patients and include compulsive water drinking, the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and the syndrome of self-induced water intoxication (SIWI). Although water intoxication was recognized nearly 70 years ago, the physiological basis of these disorders of water metabolism still remains elusive. This review will provide a historical overview, critique current studies on compulsive water drinking and SIWI, discuss possible etiologies, and present current approaches to treatment of these disorders. Because of the complexity of the subject, a review of normal water homeostasis and the SIADH will be included.

Drinking