Clozapine in the treatment of aggression in an adolescent with autistic disorder.
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Adolescent↗
Biomedical subjects
C Mazure
Publications and source records attributed to C Mazure.
Genotyping of hepatitis C virus isolates using CLIP sequencing.
Determination of hepatitis C virus (HCV) genotypes and subtypes has become increasingly important for the clinical management and prognosis of HCV infections. The aim of the present study was to assess the specificity and reliability of a newly developed, commercially available HCV genotyping kit (TRUGENE HCV 5'NC genotyping kit). This technique utilizes PCR fragments previously generated by the diagnostic Roche AMPLICOR HCV test, which are subsequently subjected to simultaneous PCR amplification and direct sequencing (CLIP sequencing) of the 5' noncoding region (5'NCR). HCV isolates from 100 randomly chosen patients were genotyped by both the TRUGENE HCV 5'NC genotyping kit and DNA enzyme immunoassay (DEIA). Typing results obtained by both methods were in complete concordance in 91% of the cases. HCV RNA from the samples with discordant genotype assignment in both assays was additionally amplified with primers from the HCV core and NS5B regions. Phylogenetic analysis of the obtained sequences supported the results obtained from DEIA in six cases and CLIP sequencing in two cases. In the former six cases, the TRUGENE HCV 5'NC genotyping kit could not correctly differentiate between subtypes of genotypes 1 and 2 due to the high conservation of the 5'NCR. However, since there was not any misclassification between HCV genotypes 1 and non-1 types, the results obtained with this system are, in general, reliable and can be used in clinical practice. The TRUGENE HCV 5'NC genotyping kit in our hands proved to be a fast and convenient technique that might be an attractive option for HCV genotyping in laboratories already using the Roche AMPLICOR HCV test for diagnostic reverse transcription-PCR.
5' Untranslated Regions↗
Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse--a preliminary report.
We have previously reported smaller hippocampal volume and deficits in short-term memory in patients with combat-related posttraumatic stress disorder (PTSD) relative to comparison subjects. The purpose of this study was to compare hippocampal volume in adult survivors of childhood abuse to matched controls. Magnetic resonance imaging was used to measure volume of the hippocampus in adult survivors of childhood abuse (n = 17) and healthy subjects (n = 17) matched on a case-by-case basis for age, sex, race, handedness, years of education, body size, and years of alcohol abuse. All patients met criteria for PTSD secondary to childhood abuse. PTSD patients had a 12% smaller left hippocampal volume relative to the matched controls (p < .05), without smaller volumes of comparison regions (amygdala, caudate, and temporal lobe). The findings were significant after controlling for alcohol, age, and education, with multiple linear regression. These findings suggest that a decrease in left hippocampal volume is associated with abuse-related PTSD.
Adult↗
Ovarian steroids and the capacity to function at home and in the workplace.
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Adult↗
The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability.
The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessive-compulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's alpha coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.
Adult↗
The Yale-Brown Obsessive Compulsive Scale. II. Validity.
The development design and reliability of the Yale-Brown Obsessive Compulsive Scale have been described elsewhere. We focused on the validity of the Yale-Brown Scale and its sensitivity to change. Convergent and discriminant validity were examined in baseline ratings from three cohorts of patients with obsessive-compulsive disorder (N = 81). The total Yale-Brown Scale score was significantly correlated with two of three independent measures of obsessive-compulsive disorder and weakly correlated with measures of depression and of anxiety in patients with obsessive-compulsive disorder with minimal secondary depressive symptoms. Results from a previously reported placebo-controlled trial of fluvoxamine in 42 patients with obsessive-compulsive disorder showed that the Yale-Brown Scale was sensitive to drug-induced changes and that reductions in Yale-Brown Scale scores specifically reflected improvement in obsessive-compulsive disorder symptoms. Together, these studies indicate that the 10-item Yale-Brown Scale is a reliable and valid instrument for assessing obsessive-compulsive disorder symptom severity and that it is suitable as an outcome measure in drug trials of obsessive-compulsive disorder.
Adult↗
Clinical implications of the pharmacokinetics of tricyclic antidepressants.
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Antidepressive Agents, Tricyclic↗
Age at onset in late-life delusional depression.
Mean age at onset was not significantly different in 39 delusional and 70 nondelusional unipolar depressed patients over 60 years of age. The finding was unchanged when sex, concurrent dementia, and medical illness were examined.
Age Factors↗
Antidepressant activity of 2-hydroxydesipramine.
We describe the relationship of 2-hydroxydesipramine (OH-DMI) plasma levels and response in a prospective DMI study in which dosage was rapidly adjusted to achieve a relatively uniform DMI plasma level. In prior studies, OH-DMI plasma levels were not related to response, but in these fixed-dose protocols the effects of OH-DMI are easily obscured by the higher concentrations of the parent drug. We hypothesized that in this study a contribution of OH-DMI to response might become apparent because DMI levels were relatively constant. Inpatients with nonpsychotic, unipolar DSM-III major depression who remained depressed (Hamilton score greater than 18) after 1 week of hospitalization without medication received a 4-week DMI trial. Twenty-four-hour drug plasma levels were used to adjust dose to reach a target DMI steady-state plasma level. Twenty-seven patients completed the trial. On every measure of response, total drug levels (DMI + OH-DMI) were more strongly correlated with outcome than were DMI levels alone. With multiple regression, both DMI and OH-DMI levels were independently and significantly associated with response. These findings suggest that OH-DMI has antidepressant activity.
Adult↗
Hydroxydesipramine in the elderly.
Elevation of the hydroxy metabolites of the tricyclic antidepressants in the elderly has been demonstrated for nortriptyline and suggested for desipramine by a study reporting elevated hydroxydesipramine (OH-DMI) plasma levels in four older patients. In the current study, patients treated with desipramine (DMI) were studied to determine whether OH-DMI was elevated in two larger samples of depressed elderly patients and to determine the magnitude of the increase, if present. In Sample I, which consisted of 68 patients of whom 23 were over 60 years of age, a fixed target dose of DMI was employed. Sample II, in which 20 of the 56 patients were over 60, received a dose adjusted to attain a fixed target DMI blood level. OH-DMI levels were higher in patients over 60 than in younger patients but the differences were not significant in either sample individually. In the two samples combined, average OH-DMI levels were 11 ng/ml higher in patients over 60 and the difference was significant (t = 2.30, p = 0.02). If variations in dose are accounted for, OH-DMI concentrations are positively correlated with age in both samples. OH-DMI/DMI ratios were not higher in the patients over 60 in these samples, but OH-DMI/DMI ratios may be higher in patients on lower doses with low DMI levels, as is common in the treatment of elderly patients. If comparable dosage is administered, nonlinear increases in DMI levels result in lower OH-DMI/DMI ratios similar to those in younger patients. Although our findings of elevated hydroxy levels in the elderly are consistent with prior reports, the clinical importance of an 11 ng/ml difference, particularly in relation to total drug levels averaging 220 ng/ml, is questioned.
Administration, Oral↗
Rapid desipramine dose adjustment using 24-hour levels.
Prior work indicates that plasma tricyclic levels obtained 24 hours after a single dose correlate well with steady state levels achieved. Although this suggests that 24-hour levels could be used to predict the dose needed to reach a desired plasma level, this method has seldom been tested prospectively. In the current study we test this strategy and determine patients' tolerance of rapid dose adjustment. First, the relationship of 24-hour levels and steady state levels in a sample of 16 inpatients was determined using a fixed dose paradigm. In a second sample of 26 depressed inpatients, plasma desipramine levels obtained 24 hours after a single test dose were applied to the regression equation derived from the first sample in order to estimate the dose needed to achieve a steady state level of 140 ng/ml. Once determined, the full dose was then rapidly administered. Sixteen of the 18 (89%) patients who completed the dose adjustment study had steady state drug concentrations within a target range of 125 to 300 ng/ml. This distribution of levels differed significantly from that previously reported for a fixed dose sample in which only 19 of 83 (23%) patients had levels within this range. Dose adjustment using 24-hour levels was well tolerated and should help to attain a more rapid response to antidepressant treatment. This has important implications for reducing lengths of hospitalization for depressed inpatients. The technique should also prove useful in research where a uniform plasma level paradigm is desirable.
Adult↗
Reliability and validity of the symptoms of major depressive illness.
In two consecutive studies, we examined the interrater reliability and then the concurrent validity of interview ratings for individual symptoms of major depressive illness. The concurrent validity of symptoms was determined by assessing the degree to which symptoms observed or reported during an interview were observed in daily behavior. Results indicated that most signs and symptoms of major depression and melancholia can be reliably rated by clinicians during a semistructured interview. Ratings of observable symptoms (signs) assessed during the interview were valid indicators of dysfunction observed in daily behavior. Several but not all ratings based on patient report of symptoms were at variance with observation. These discordant patient-reported symptoms may have value as subjective reports but were not accurate descriptions of observed dysfunction.
Adolescent↗
Ruminative thinking. A distinctive sign of melancholia.
We propose that ruminative thinking, the tendency to dwell on the same thought or theme, is useful for distinguishing melancholic from nonmelancholic major depression. We demonstrate that the symptom can be rated reliably and that interview ratings are concordant with ward observation of the symptom. The frequency of ruminative thinking, rated retrospectively in a prior study, was 60% in 75 patients having autonomous depression while only 18% of 48 nonautonomous patients were so affected. In this study, we found that ruminative thinking, prospectively rated in 71 patients with unipolar major depression, was present in 53% of patients with DSM-III melancholia but only 11% of the nonmelancholic patients. The presence of ruminative thinking appears to be useful for making the diagnosis of melancholia and its definition may facilitate study of the psychobiology of this disorder.
Delusions↗
Psychological interviews in screening couples undergoing in vitro fertilization.
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Attitude to Health↗
Desipramine plasma levels and response in elderly melancholic patients.
The relationship of response and plasma desipramine concentrations was examined in elderly depressed patients to determine whether they were more sensitive to the antidepressant effects of the drug and whether they would respond at lower plasma concentrations than younger patients. Twenty-five inpatients over the age of 60, who met criteria for major depression with melancholia, were unipolar, were not delusional, were without active medical illness or definite brain disease, and were still depressed after 1 week of hospitalization off psychotropic drugs, were treated with desipramine (2.5 mg/kg) for 3 weeks. Of the 18 patients completing the drug trial, six responded and 12 did not. Desipramine levels of responders (median, 126 ng/ml) were higher than those of nonresponders (median, 81 ng/ml; Mann-Whitney test, p less than 0.05). The threshold for response was the same as the threshold (115 ng/ml) observed in 31 nondelusional melancholic patients under the age of 60 treated in a similar manner with desipramine. Among elderly patients with levels above 115 ng/ml, four of five responded, and below this level, two of 13 responded (Fisher's exact test, p less than 0.025). Five patients not responding to the initial 3-week trial responded when desipramine was increased and the plasma level rose above 115 ng/ml. The data indicate that elderly melancholic patients to not respond to lower desipramine plasma concentrations and that therapeutic levels are similar to those for younger melancholic patients. The doses of desipramine needed to reach these levels were also similar to those required in younger patients.
Adult↗
Drug-responsive symptoms in melancholia.
Depressive symptoms present in 43 patients with unipolar nondelusional melancholia were studied to determine which symptoms were the best measures of response to desipramine hydrochloride. An extended Hamilton Depression Scale was used to identify symptoms that were present frequently. We then determined which symptoms improved in direct relation to achievement of therapeutic plasma desipramine concentrations, using multiple regression analysis to account for pretreatment symptom severity. In ten symptoms, improvement was significantly associated with desipramine treatment. These ten symptoms seem to be the best measure of drug response during tricyclic antidepressant treatment in patients with nondelusional melancholia.
Delusions↗
The role of the social worker in the in-vitro fertilization program.
The role of the clinical social worker in the In-Vitro fertilization Program is to help provide patients with an environment that includes realistic expectation and emphasizes the emotional spectrum of euphoria, anxiety and dysphoria that can accompany the demanding protocol. The literature supports the need for counseling and supportive psychotherapy in the infertility clinic but has not dealt specifically with the psychological demands of In-Vitro fertilization. This paper addresses the emotional stress of in-vitro fertilization and emphasizes the role of social worker as counselor, educator and guide.
Adaptation, Psychological↗
Blindness and reliability in lifetime psychiatric diagnosis.
Confidence in the assignment of lifetime psychiatric diagnosis is of great importance to genetic studies of psychiatric illness. To establish the credibility of a lifetime psychiatric history obtained via a structured interview, two paradigms were constructed to estimate reproducibility of the interview recording process. The first paradigm, simultaneous coding, was used to test comparability of four interviewers independently coding an interview form. Low variance/high reliability was demonstrated. The second paradigm, test-retest, provided for each subject to be interviewed twice, with a mean interim time of 6.7 months (SEM = .39). This paradigm demonstrated high reproducibility of psychiatric diagnosis over time. The overall k value for measurement of diagnostic agreement was .79. Only the diagnostic category of minor depression seemed to evade reliability. It was shown across both paradigms that an interviewer need not be blind (naive to previously held diagnosis) to obtain an unbiased interview. However, it is still recommended that the diagnosis of each interview should be determined by an independent diagnostician.
Adult↗