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S A Rasmussen

Publications and source records attributed to S A Rasmussen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mirtazapine augmentation in the treatment of refractory depression.

BACKGROUND: Pharmacotherapeutic strategies that target specific actions at multiple neuronal receptors or cellular components may offer a superior approach for treatment of refractory depression. Mirtazapine is a novel antidepressant which has a mechanism that involves the enhancement of noradrenergic and serotonergic neurotransmission via blockade of alpha2-adrenergic autoreceptors and heteroreceptors without activity at the serotonin transporter. Mirtazapine is thus a compelling candidate for augmentation treatment in patients who fail to achieve adequate response with other antidepressant medications. METHOD: Twenty patients with DSM-IV major depression or dysthmia who had persistent depressive syndromes despite at least 4 weeks of standard antidepressant pharmacotherapy were given augmentation with mirtazapine (15 to 30 mg p.o. q.h.s.) on an open-label basis. Clinical assessments of status at baseline, 2 weeks, and 4 weeks were used to rate response. RESULTS: Forty-five percent (N = 9) of the sample were responders at 2 weeks. At the 4 week follow-up, 55% (N = 11) were responders, 30% (N = 6) were nonresponders, and 15% (N = 3) had discontinued treatment owing to side effects. Common side effects included weight gain and sedation. CONCLUSION: These data suggest that the addition of mirtazapine may be beneficial for patients who have refractory depression, but side effects are prominent at the doses we used. Controlled trials to further evaluate the efficacy and safety of mirtazapine augmentation are needed.

Adrenergic alpha-Antagonists↗
PubMed1999

Patterns of remission and relapse in obsessive-compulsive disorder: a 2-year prospective study.

OBJECTIVE: This study examined the course of illness in patients with obsessive-compulsive disorder (OCD) over a 2-year period. METHOD: Sixty-six patients with a primary diagnosis of DSM-III-R OCD were followed prospectively for 2 years. Baseline information was collected on demographic characteristics, Axis I and II diagnoses, and severity of OCD symptoms. Follow-up measures obtained at 3, 6, 12, and 24 months after baseline assessment included information on symptomatic and diagnostic status as well as behavioral and somatic treatments received. RESULTS: The probability of full remission from OCD over the 2-year period was 12%. The probability of partial remission was 47%. After achieving remission from OCD, the probability of relapse was 48%. No factors were identified that significantly predicted full or partial remission. Seventy-seven percent (N = 51) of the subjects received a serotonin reuptake inhibitor (SRI) for > or =12 weeks, and 68% (N = 45) received medium-to-high doses of SRIs for > or =12 weeks. Only 18% received a full trial of behavior therapy. CONCLUSION: Despite exposure to at least 1 adequate trial of an SRI, the likelihood of full remission of OCD in this study was low. Results of this study also suggest that behavior therapy may be under-utilized.

Adult↗
PubMed1998

Prevalence of 22q11 region deletions in patients with velopharyngeal insufficiency.

Velo-cardio-facial syndrome, DiGeorge syndrome, conotruncal anomaly face syndrome, tetralogy of Fallot, and pulmonary atresia with ventricular septal defect are all associated with hemizygosity of 22q11. While the prevalence of the deletions in these phenotypes has been studied, the frequency of deletions in patients presenting with velopharyngeal insufficiency (VPI) is unknown. We performed fluorescence in situ hybridization for locus D22S75 within the 22q11 region on 23 patients with VPI (age range 5-42 years) followed in the Craniofacial Clinic at the University of Florida. The VPI occurred either as a condition of unknown cause (n=16) or as a condition remaining following primary cleft palate surgery (n=7). Six of sixteen patients with VPI of unknown cause and one of seven with VPI following surgery had a deletion in the region. This study documents a high frequency of 22q11 deletions in those presenting with VPI unrelated to overt cleft palate surgery and suggests that deletion testing should be considered in patients with VPI.

Adolescent↗
PubMed1998

A novel mutation (V191G) in a German-British type 1 Gaucher disease patient. Mutations in brief no. 131. Online.

Gaucher disease results from mutations in the glucocerebrosidase gene located on human chromosome 1q21. Three clinical forms of Gaucher disease have been described: type 1, nonneuropathic; type 2, acute neuropathic; and type 3, subacute neuropathic. We have identified a novel mutation in a German-British patient with type 1 Gaucher disease which results in V191G of the glucocerebrosidase polypeptide. Because the mutation abolishes a HphI cleavage site, its presence was confirmed by HphI RFLP analysis of PCR-amplified genomic DNA. In the second allele of the patient, the mutation identified was g.5841A G(N370S). Sequence analysis of the remainder of the coding region of the gene as well as the exon-intron boundaries showed identity to normal controls. Because mutation N370S has so far been found only in type 1 Gaucher disease and postulated to result in mild clinical presentation, and since the clinical course of this patient has been relatively mild with minimal skeletal involvement, we speculate that the V191G/N370S genotype may also result in good prognosis.

Chromosomes, Human, Pair 1↗
PubMed1998

Long-term use of high-dose benzoate and dextromethorphan for the treatment of nonketotic hyperglycinemia.

OBJECTIVE: The objective of this study was to test the hypotheses that reduction of glycine and blocking of the N-methyl-D-aspartate receptor channel complex would be beneficial for both seizure reduction and developmental progress in patients with nonketotic hyperglycinemia. METHODS: We administered benzoate (at doses of 500 to 750 mg/kg/day) and dextromethorphan (at doses of 3.5 to 22.5 mg/kg/day) to four infants with nonketotic hyperglycinemia with follow-up of 3 months to 6 years. RESULTS: Benzoate reduced to normal the glycine concentration in plasma and substantially reduced but did not normalize the glycine concentration in cerebrospinal fluid. Dextromethorphan was a potent anticonvulsant in some but not all patients. There was remarkable interpatient variability in dextromethorphan metabolism. Three patients are living (ages ranging from 4 to 6 years) and are moderately to severely developmentally delayed; two are free of seizures. The third patient, with the slowest development, had intractable seizures for nearly a month before diagnosis, and although seizure-free for 30 months, now has grand-mal seizures. One patient died of intractable seizures at 3 months. CONCLUSIONS: These outcomes suggest that benzoate and dextromethorphan are not uniformly effective in nonketotic hyperglycinemia, but for some patients they improve arousal, decrease or eliminate seizures, and allow for some developmental progress. Trials with additional patients and other receptor channel blockers are warranted.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Genetic disease in offspring of long-term survivors of childhood and adolescent cancer.

Numerous case series have addressed the concern that cancer therapy may damage germ cells, leading to clinical disease in offspring of survivors. None has documented an increased risk. However, the methodological problems of small series make it difficult to draw firm conclusions regarding the potential of cancer treatments to damage the health of future offspring. We conducted a large interview study of adult survivors of childhood cancer treated before 1976. Genetic disease occurred in 3.4% of 2,198 offspring of survivors, compared with 3.1% of 4,544 offspring of controls (P=.33; not significant); there were no statistically significant differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with survivors not so treated showed no association with sporadic genetic disease (P=.49). The present study provides reassurance that cancer treatment using older protocols does not carry a large risk for genetic disease in offspring conceived many years after treatment. With 80% power to detect an increase as small as 40% in the rate of genetic disease in offspring, this study did not do so. However, we cannot rule out the possibility that new therapeutic agents or specific combinations of agents at high doses may damage germ cells.

Adolescent↗
PubMed1998

Constitutional and mosaic large NF1 gene deletions in neurofibromatosis type 1.

A set of neurofibromatosis type 1 (NF1) patients was screened for large NF1 gene deletions by comparing patient and parent genotypes at 10 intragenic polymorphic loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases), five (7.5%) showed loss of heterozygosity (LOH), indicative of NF1 gene deletion. These five patients did not have severe NF1 manifestations, mental retardation, or dysmorphic features, in contrast to previous reports of large NF1 deletions. All five deletions were de novo and occurred on the maternal chromosome. However, two patients showed partial LOH, consistent with somatic mosaicism for the deletion, suggesting that mosaicism may be more frequent in NF1 than previously recognised (and may have bearing on clinical severity). We suggest that large NF1 deletions (1) are not always associated with unusual clinical features, (2) tend to occur more frequently on maternal alleles, and (3) are an important mechanism for constitutional and somatic mutations in NF1 patients.

Adult↗
PubMed1998

The Brown Assessment of Beliefs Scale: reliability and validity.

OBJECTIVE: The authors developed and evaluated the reliability and validity of the Brown Assessment of Beliefs Scale, a clinician-administered seven-item scale designed to assess delusions across a wide range of psychiatric disorders. METHOD: The authors developed the scale after reviewing the literature on the assessment of delusions. Four raters administered the scale to 20 patients with obsessive-compulsive disorder (OCD), 20 patients with body dysmorphic disorder, and 10 patients with mood disorder with psychotic features. Audiotaped interviews of scale administration conducted by one rater were independently scored by the other raters to evaluate interrater reliability. The scale was administered to 27 patients twice to determine test-retest reliability. Other insight instruments as well as scales that assess symptom severity were administered to assess convergent and discriminant validity. Sensitivity to change was assessed in a multicenter treatment study of sertraline for OCD. RESULTS: Interrater and test-retest reliability for the total score and individual item scores was excellent, with a high degree of internal consistency. One factor was obtained that accounted for 56% of the variance. Scores on the Brown Assessment of Beliefs Scale were not correlated with symptom severity but were correlated with other measures of insight. The scale was sensitive to change in insight in OCD but was not identical to improvement in severity. CONCLUSIONS: The Brown Assessment of Beliefs Scale is a reliable and valid instrument for assessing delusionality in a number of psychiatric disorders. This scale may help clarify whether delusional and nondelusional variants of disorders constitute the same disorder as well as whether delusionality affects treatment outcome and prognosis.

1-Naphthylamine↗
PubMed1998

A time-limited behavioral group for treatment of obsessive-compulsive disorder.

In vivo exposure with response prevention is an effective treatment for obsessive-compulsive disorder (OCD) either alone or combined with pharmacotherapy. Widespread application of this technique has been limited by lack of trained therapists and the expense of intensive individual behavioral therapy. This report describes a time-limited 10-session behavioral therapy group for OCD whose key elements are exposure, response prevention, therapist and participant modeling, and cognitive restructuring. In a naturalistic open trial of 90 patients meeting DSM-III-R criteria for OCD who completed the 10-session group, self-administered Yale-Brown Obsessive-Compulsive Scale scores (mean +/- SD) were 21.8 +/- 5.6 at baseline and 16.6 +/- 6.4 after the 10-week treatment, a significant decrease. A descriptive analysis of the therapeutic elements of the group and its advantages over individual behavioral treatment are presented.

Adult↗
PubMed1997

Segregation of a familial balanced (12;10) insertion resulting in Dup(10)(q21.2q22.1) and Del(10)(q21.2q22.1) in first cousins.

An interchromosomal insertion in 3 generations of a family was ascertained through two developmentally delayed first cousins. Cytogenetic analysis using G-banding and chromosome painting showed an apparently balanced direct insertion of chromosome 10 material into chromosome 12, ins(12;10)(q15;q21.2q22.1), in the mothers and grandfather of these children. The proposita inherited only the derivative 10 chromosome, resulting in deletion of 10q21.2 --> 22.1 while her cousin inherited only the derivative 12, resulting in duplication of 10q21.2 --> 22.1. A comparison of the proposita with published deletion cases suggests a pattern of anomalies attributable to deletion of the 10q21 --> q22 region: developmental delay, hypotonia, a heart murmur, telecanthus, broad nasal root and ear abnormalities. This is the first report of a nontandem duplication of the 10q21 --> q22 region. The phenotype of the cousin with the duplication does not overlap greatly with published tandem 10q duplications. Finally, this report reaffirms the importance of obtaining family studies of patients with interstitial chromosomal abnormalities.

Chromosomes, Human, Pair 10↗
PubMed1997

NF1 mutation analysis using a combined heteroduplex/SSCP approach.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder characterized predominantly by neurofibromas, café-au-lait spots, and Lisch nodules. The disease is caused by disruptive mutations of the large NF1 gene, with half of cases caused by new mutation. Less than 100 constitutional mutations have thus far been published, ranging from very large deletions to point mutations. We have pursued NF1 mutation analysis by heteroduplex analysis (HDA) and single-strand conformational polymorphism analysis (SSCP) of individual exons. We streamlined these techniques to eliminate the use of radioactivity, to apply both methods to the same PCR product, and to multiplex samples in gels. Applied simultaneously to a set of 67 unrelated NF1 patients, HDA and SSCP have thus far identified 26 mutations and/or variants in 45 of the 59 exons tested. Disease-causing mutations were found in 19% (13/67) of cases studied. Both techniques detected a variety of mutations including splice mutations, insertions, deletions, and point changes, with some overlap in the ability of each method to detect variants.

Base Sequence↗
PubMed1997

Moclobemide in social phobia: a controlled dose-response trial.

Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed.

Adult↗
PubMed1997

Clinical features of obsessive-compulsive disorder in elderly patients.

There has been no systematic study of the clinical features of obsessive-compulsive disorder (OCD) in elderly patients. This study describes the symptoms and characteristics of OCD among 32 outpatients age 60 or older and 601 younger patients meeting DSM-III-R criteria and given the Yale-Brown Obsessive-Compulsive Scale (YBOCS), NIMH scale, and a 41-item symptom questionnaire. Elderly patients had a later age at onset compared with younger patients. No differences were found in severity of symptoms on the YBOCS. Elderly patients had fewer concerns about symmetry, need to know, and counting rituals. Handwashing and fear of having sinned were more common. There were few differences in clinical features of OCD among the elderly patients compared with younger OCD patients.

Adult↗
PubMed1997

Obsessive-compulsive disorder in patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: The authors evaluated the frequency of DSM-III-R obsessive-compulsive disorder in patients with a primary diagnosis of schizophrenia or schizoaffective disorder. METHOD: Patients with schizophrenia (N = 52) or schizoaffective disorder (N = 25) were evaluated for the presence of obsessions and compulsions by means of the Structured Clinical Interview for DSM-III-R, the Yale-Brown Obsessive Compulsive Scale, chart review, and contact with the treating clinicians. RESULTS: Six (7.8%) of the 77 patients met the DSM-III-R criteria for both obsessive-compulsive disorder and schizophrenia or schizoaffective disorder. CONCLUSIONS: These findings suggest that obsessive-compulsive disorder occurs in a substantial percentage of patients with schizophrenia or schizoaffective disorder. The addition of medications targeted at obsessive-compulsive disorder may be beneficial to these patients but requires systematic evaluation.

Adult↗
PubMed1997

Symptoms of obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder encompasses a broad range of symptoms that represent multiple psychological domains, including perception, cognition, emotion, social relatedness, and diverse motor behaviors. The purpose of these analyses was to evaluate the correlational relationships of the symptoms of obsessive-compulsive disorder. METHOD: This study examined the 13 a priori categories used to group types of obsessions and compulsions in the Yale-Brown Obsessive Compulsive Scale symptom checklist in two independent groups of patients with obsessive-compulsive disorder (N = 208 and N = 98). A principal-components factor analysis with varimax rotation was performed, followed by a series of other exploratory analyses. RESULTS: The two data sets yielded nearly identical results. Four factors--obsessions and checking, symmetry and ordering, cleanliness and washing, and boarding--emerged in each data set, in total accounting for more than 60% of the variance. CONCLUSIONS: Obsessive-compulsive disorder is a multidimensional and etiologically heterogeneous condition. The four symptom dimensions identified in this study are largely congruent with those identified in earlier reports. These factors may be of value in future genetic, neurobiological, and treatment response studies.

Adult↗
PubMed1997

A severity rating scale for body dysmorphic disorder: development, reliability, and validity of a modified version of the Yale-Brown Obsessive Compulsive Scale.

The authors developed the Yale Brown Obsessive Compulsive Scale Modified for Body Dysmorphic Disorder (BDD-YBOCS), a 12-item semistructured clinician-rated instrument designed to rate severity of body dysmorphic disorder (BDD). The scale was administered to 125 subjects with BDD, and interviews with 15 subjects were rated by 3 other raters. Test-retest reliability was assessed in 30 subjects. Other scales were administered to assess convergent and discriminant validity, and sensitivity to change was evaluated in a study of fluvoxamine. Each item was frequently endorsed across a range of severity. Good interrater reliability, test-retest reliability, and internal consistency were obtained. BDD-YBOCS scores correlated with global severity scores but not with a measure of general psychopathology; they were modestly positively correlated with depression severity scores. Three factors accounted for 59.6 percent of the variance. The scale was sensitive to change in BDD severity. The BDD-YBOCS appears to be a reliable and valid measure of BDD severity and is a suitable outcome measure in treatment studies of BDD.

Adult↗
PubMed1997

Treatment strategies for chronic and refractory obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD), despite our increasing understanding of its causes and its effective treatment, remains a chronic and underdiagnosed disorder. Both treatment with SSRIs and the behavioral treatment strategy of exposure with response prevention have been proved by clinical trials to be effective and safe in treating OCD; however, even these treatments sometimes elicit only moderate patient response, and some OCD patients do not respond to them at all. Preliminary data suggest that OCD has lifelong persistence and that discontinuation of pharmacotherapy often leads to relapse. Nonetheless, further prospective, controlled, maintenance studies of OCD are needed to determine factors in and predictors of recovery, remission, and relapse. Finally, new procedures for treatment-refractory patients are needed; neurosurgical and new pharmacologic approaches have shown promise in treating these patients and should be studied in controlled trials.

Behavior Therapy↗