ABSTRACT
A study was conducted to examine the tolerability and pharmacokinetics of single and multiple oral doses of L-365,260, a novel antagonist for type B cholecystokinin (CCK) receptors and to quantify effects of selective blockade of type B CCK receptors through treatment with L-365,260 on measures of anxiety, hunger, and cognitive performance. Healthy volunteers were given single oral doses of up to 50 mg of L-365,260 and multiple oral doses of up to 25 mg every 6 hours for 10 days. Plasma concentrations of L-365,260 were quantified by means of high-performance liquid chromatography. Anxiety and hunger were assessed by visual analog scale and the Spielberger State Anxiety Index. Cognitive testing was used to evaluate attention level and short-term memory. L-365,260 was rapidly absorbed and a biphasic pattern of elimination was demonstrated with a terminal half-life (t1/2) of 8 to 12 hours. The mean (n = 6) values for peak plasma concentration (C(max)) and time to peak concentration (t(max)) of L-365,260 were 503 ng/mL and 1.25 hours, respectively, after a single 50-mg oral dose. Accumulation of L-365,260 plasma concentrations was seen after the prescribed multiple-dose regimens. Steady state was achieved after 3 days of oral administration. L-365,260 had an acceptable tolerability profile after oral administration. No changes in measures of anxiety, hunger, or short-term memory were observed at doses of L-365,260 shown to have antagonist activity at the CCK-B receptor.
Subject(s)
Benzodiazepinones/pharmacokinetics , Phenylurea Compounds , Administration, Oral , Adult , Anxiety/drug therapy , Benzodiazepinones/adverse effects , Benzodiazepinones/blood , Cognition/drug effects , Humans , Hunger/drug effects , Male , Memory, Short-Term/drug effectsABSTRACT
OBJECTIVES: To evaluate the effect of selective blockade of type B cholecystokinin receptors on gall bladder contraction in normal humans and to compare methods for quantitative analysis of gall bladder contraction. METHODS: L-365,260, a novel, nonpeptide cholecystokinin antagonist shown to be selective for type B cholecystokinin receptors, was administered every 6 h over a 5-7 day period. Plasma levels of L-365,260 were determined by high pressure liquid chromatography. Gallbladder contraction after a standardized fatty meal was measured by ultrasonography, and results were calculated by ellipsoid or sum of cylinders methods. RESULTS: L-365,260 levels were comparable to levels in earlier studies demonstrating inhibition of pentagastrin-stimulated acid secretion in normal subjects and blockade of anxiogenic effects of cholecystokinin injections in patients with panic disorder. Regardless of the method used for estimating gallbladder size, none of the L-365,260 doses studied inhibited gallbladder contraction. Gallbladder size was most consistently estimated by the ellipsoid method using measurements normalized to individual values for minimum and maximum gallbladder dimensions. CONCLUSIONS: Multiple oral doses of L-365,260 do not alter ultrasonographically assessed gallbladder contraction at doses shown to be clinically effective in earlier studies. Despite being more difficult to implement, the sum of cylinders method for estimating gall bladder size offers no advantage over the ellipsoid method.
Subject(s)
Benzodiazepinones/pharmacology , Gallbladder Emptying/drug effects , Phenylurea Compounds , Receptors, Cholecystokinin/antagonists & inhibitors , Adult , Aged , Analysis of Variance , Benzodiazepinones/blood , Dose-Response Relationship, Drug , Double-Blind Method , Female , Gallbladder/diagnostic imaging , Humans , Male , Middle Aged , Receptors, Cholecystokinin/drug effects , Reference Values , Time Factors , UltrasonographyABSTRACT
OBJECTIVE: The authors examined the (under) utilization of the psychiatric consultation service for patients aged sixty to seventy-five who were hospitalized for medical reasons, and explored whether one could retrospectively document and identify a greater need for psychological support than the one reflected in the number of actual consultations requested. Three questions were addressed: 1) the psychiatric consultation rate; 2) the frequency of unrecognized medical, psychiatric, and psychosocial complicating factors; and 3) whether the distribution of these factors differed by gender. METHOD: Records of 203 consecutively-admitted elderly patients hospitalized on medical wards were reviewed by two experienced general hospital psychiatrists for any indication of medical, psychiatric, and psychosocial risk factors. The frequency of actual psychiatric consultations was also recorded. RESULTS: Three or more risk factors were noted in the records of 36 percent of all patients. Consultation was sought for only 3 percent. Gender differences in type and distribution of risk factors were identified. CONCLUSIONS: Indicators and profiles that define probable need for psychiatric consultation were identified and briefly discussed. More well-designed, prospective studies testing these indicators and profiles are needed.
Subject(s)
Aged , Anxiety Disorders/psychology , Depressive Disorder/psychology , Health Services Needs and Demand , Referral and Consultation , Anxiety Disorders/classification , Anxiety Disorders/diagnosis , Depressive Disorder/classification , Depressive Disorder/diagnosis , Female , Geriatric Psychiatry , Geriatrics , Health Services for the Aged , Humans , Male , Psychiatric Status Rating Scales , Retrospective Studies , Risk FactorsABSTRACT
Eight hundred and forty one patients with 1,135 consecutive admissions to a university-affiliated mental health center were studied to examine patterns of treatment program use. Twenty two percent of patients had repeat admissions accounting for 42% of hospital episodes. Single admission and repeater groups are compared, and differences among repeater subgroups with progressively greater numbers of admissions per patient are described. Only 10 patients with the highest number of admissions during the study period also were very high utilizers of all services (inpatient, crisis, day hospital, regional chronic state hospital). These patients' characteristics are discussed with implications for future study.
Subject(s)
Community Mental Health Centers/statistics & numerical data , Mental Disorders/therapy , Adolescent , Adult , Aged , Educational Status , Female , Humans , Length of Stay , Male , Marriage , Middle Aged , Patient Readmission/statistics & numerical data , Psychiatric Status Rating Scales , Sex FactorsABSTRACT
For the attention of psychiatric consultants, brodifacoum, a new longer-acting, warfarin-like oral anticoagulant rodenticide, has been used for suicide attempts. The overdose potential with brodifacoum is serious since it is readily available without prescription, and bleeding complications last for weeks to months after a single ingestion. This article reports a case of ingestion and reviews four similar cases from medical literature. Also reviewed are details about mechanism of action, procedures for diagnosis, and treatment requirements. Also, characteristics of persons who ingest long-acting anticoagulants appear to differ from those who ingest short-acting anticoagulants reported from earlier literature.
Subject(s)
4-Hydroxycoumarins/poisoning , Anticoagulants , Factitious Disorders/diagnosis , Hemorrhagic Disorders/diagnosis , Rodenticides , Factitious Disorders/psychology , Humans , Male , Middle Aged , Suicide, Attempted/psychology , Vitamin K/antagonists & inhibitorsABSTRACT
Using either haloperidol or perphenazine in a fixed-dose protocol, plasma free homovanillic acid (HVA) and methoxyhydroxyphenethylglycol (MHPG) were decreased in 37 nonorganic psychotic inpatients at neuroleptic steady state (7-9 days) in comparison with pretreatment values. The data indicate that the magnitude of the decline in HVA and MHPG was associated with treatment response and not with neuroleptic plasma levels.
Subject(s)
Glycols/blood , Haloperidol/therapeutic use , Homovanillic Acid/blood , Methoxyhydroxyphenylglycol/blood , Perphenazine/therapeutic use , Psychotic Disorders/drug therapy , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Psychotic Disorders/bloodABSTRACT
We describe a group of psychotic patients who became worse early in the course of neuroleptic treatment. Characteristics of this group were: predominantly female sex, relatively brief onset, family history of affective disorder, hypomotoric presentation, and severe neuroleptic side effects. We propose that some patients with affective psychoses are uniquely susceptible to profound blockade of the nigrostriatal dopaminergic system by neuroleptics.
Subject(s)
Antipsychotic Agents/adverse effects , Psychoses, Substance-Induced/etiology , Psychotic Disorders/drug therapy , Adolescent , Adult , Antipsychotic Agents/therapeutic use , Benztropine/therapeutic use , Chlorpromazine/adverse effects , Dyskinesia, Drug-Induced/etiology , Female , Haloperidol/adverse effects , Humans , Male , Thiothixene/adverse effectsSubject(s)
Emergency Medical Services , Emergency Services, Psychiatric/statistics & numerical data , Mental Health Services/statistics & numerical data , Patients/psychology , Triage , Adult , Aged , Aged, 80 and over , Connecticut , Emergency Services, Psychiatric/organization & administration , Female , Humans , Male , Middle Aged , Patient Compliance , Patient Readmission , Socioeconomic Factors , Substance-Related Disorders/diagnosisABSTRACT
The authors measured plasma levels of free homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenyl-glycol (MHPG) in 350 consecutive psychiatric patients. Among the 22 patients with the highest values for both HVA and MHPG, the primary diagnoses were psychotic disorders, eating disorders, and major depression.
Subject(s)
Glycols/blood , Homovanillic Acid/blood , Mental Disorders/diagnosis , Methoxyhydroxyphenylglycol/blood , Adolescent , Adult , Aged , Aged, 80 and over , Depressive Disorder/blood , Depressive Disorder/diagnosis , Feeding and Eating Disorders/blood , Feeding and Eating Disorders/diagnosis , Female , Hospitalization , Humans , Male , Mental Disorders/blood , Middle Aged , Psychotic Disorders/blood , Psychotic Disorders/diagnosisABSTRACT
Twenty-one patients hospitalized for acute non-organic psychosis were treated with a fixed daily dose of haloperidol (0.2 mg/kg) for 10 days. Serum levels of haloperidol were significantly lower in the male patients at steady state as compared to females. Serum levels at 24 h and 48 h were highly correlated steady-state levels. Haloperidol levels at steady state were significantly correlated with global outcome at 10 days. Prolactin at haloperidol steady state was significantly related to global outcome at 10 days in the males. Pretreatment plasma free HVA but not MHPG was significantly related to outcome in males and females.
Subject(s)
Haloperidol/blood , Psychotic Disorders/blood , Adult , Aged , Female , Haloperidol/therapeutic use , Homovanillic Acid/blood , Humans , Male , Methoxyhydroxyphenylglycol/blood , Middle Aged , Prolactin/blood , Psychotic Disorders/drug therapy , Sex FactorsABSTRACT
Forty-seven psychotic inpatients who required neuroleptic treatment were studied with respect to some clinical and biochemical variables associated with early neuroleptic response. Compared to poor early responders, good responders were older at onset of illness and at index admission, less likely to have had a schizoid developmental history, and more likely to be married. There was a trend for good early responders to have received a diagnosis of affective psychosis or atypical psychotic disorder rather than schizophrenia or schizophreniform disorder. However, no behavioral symptom or sign differentiated good from poor early responders with the possible exception of pretreatment psychomotor retardation, which showed some association with poor response. Fasting plasma-free homovanillic acid was significantly higher in the good response group and 3-methoxy-4-hydroxyphenethylene glycol showed a similar trend.
Subject(s)
Antipsychotic Agents/therapeutic use , Glycols/blood , Homovanillic Acid/blood , Methoxyhydroxyphenylglycol/blood , Adolescent , Adult , Age Factors , Aged , Female , Humans , Male , Middle AgedSubject(s)
Glycols/blood , Homovanillic Acid/blood , Methoxyhydroxyphenylglycol/blood , Psychotic Disorders/blood , Adult , Age Factors , Fasting , Female , Hospitalization , Humans , Male , Sex FactorsSubject(s)
Baclofen/adverse effects , Substance Withdrawal Syndrome/etiology , Substance-Related Disorders/etiology , Adolescent , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
Fifty psychiatric inpatients aged 50 and over, with no hard neurologic findings, and with a variety of DSM-III diagnoses (adjustment disorder, affective illness, and dementia), were rated for behavioral and psychiatric symptoms using the Geriatric Rating Scale and the Nurse's Assessment of Global Symptomatology-Elderly. These clinical ratings were correlated with computed tomographic (CT) scan assessments of various superficial cerebral regions as well as with linear measures of ventricular size. Behavioral deficits in activities of daily living (ADL) plus an interactional variable, inability to respond to requests, were correlated with superior temporal and inferior parietal CT abnormalities, particularly on the left side. Suspiciousness and peculiar thinking, mood lability and irritability, as well as impaired memory with confusion, perplexity, and disorientation were also associated with atrophy in these same regions. Prefrontal area defects correlated with mood lability and deficits in visual-interactional responsiveness. Statistically controlling for effects of age and alcohol abuse did not alter the basic nature of these results. Regional cerebral specialization in relation to these results are discussed using concepts developed by Luria.
Subject(s)
Cerebral Cortex/diagnostic imaging , Mental Disorders/diagnosis , Social Behavior , Tomography, X-Ray Computed , Activities of Daily Living , Aged , Atrophy , Female , Frontal Lobe/diagnostic imaging , Humans , Male , Middle Aged , Parietal Lobe/diagnostic imaging , Social Behavior Disorders/diagnosis , Temporal Lobe/diagnostic imagingABSTRACT
The ratio of the increase in serum prolactin concentration to steady-state haloperidol concentration in acutely psychotic women correlated with early clinical improvement. Correction of prolactin response for neuroleptic concentration may provide a better clinical predictor than either measure alone.