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Biomedical subjects

L C Barr

Publications and source records attributed to L C Barr.

At least 19 recordsLinked to original sources
PubMed1999

Possible role of neuropeptides in obsessive compulsive disorder.

The most consistent finding in clinical research of obsessive compulsive disorder (OCD) is the significant treatment advantage of potent serotonin uptake inhibitors (SUIs) over other classes of antidepressant and antianxiety drugs. Clinical neurobiological studies of OCD, however, have yielded limited and inconsistent evidence for significant fundamental abnormalities in monoamine systems including serotonin, norepinephrine and dopamine. Furthermore, one-third to one-half of OCD patients do not experience a clinically meaningful improvement with SUI treatment. Investigation beyond the monoamine systems may be necessary in order to more fully understand the pathophysiology of obsessive-compulsive symptoms and develop improved treatments. Evidence from preclinical studies suggests that neuropeptides may have important influences on memory acquisition, maintenance and retrieval; grooming, maternal, sexual and aggressive behavior; fixed action patterns; and stereotyped behavior; these phenomena may relate to some features of OCD. In addition, extensive interactions have been identified in the brain between neuropeptidergic and monoaminergic systems, including co-localization among specific populations of neurons. The purpose of this review is to present the current knowledge of the role of neuropeptides in the clinical neurobiology of children, adolescents and adults with OCD focusing primarily on results from pharmacological challenge and cerebrospinal fluid studies. Where evidence exists, developmentally regulated differences in neuropeptide function between children and adolescents versus adults with OCD will be emphasized; these data are intended to underscore the potential importance of establishing the age of symptom onset (childhood versus adult) in individual patients with OCD participating in clinical neurobiological investigations. Likewise, where information is available, differences in measures of neuropeptides between patients with non-tic-related OCD versus tic-related OCD will be highlighted; these data will demonstrate the critical value of diagnostic precision, as these two particular subtypes of OCD may have different neurochemical underpinnings.

Adolescent↗
PubMed1997

Effects of fluoxetine administration on mood response to tryptophan depletion in healthy subjects.

Short-term reduction in plasma tryptophan (tryptophan depletion) produces a relapse of depressive symptoms in 60% of previously depressed patients recently recovered with serotonin reuptake inhibitor treatment. Tryptophan depletion does not consistently increase depressive symptoms in unmedicated depressed patients or in depressed patients whose symptoms are remitted with a norepinephrine reuptake inhibitor. These data suggest that serotonin reuptake inhibitor treatment itself may confer vulnerability to the development of depressive symptoms during tryptophan depletion. In order to further investigate this possibility, six healthy individuals underwent double-blind placebo-controlled tryptophan depletion before and following six weeks of treatment with fluoxetine 20 mg/day. No increased vulnerability to the mood-lowering effects of tryptophan depletion occurred as a result of fluoxetine treatment. Additionally, fluoxetine treatment itself was not associated with changes in mood or quality of life in these healthy volunteers. These data indicate that serotonin reuptake inhibitor treatment alone does not produce the depressive effects of tryptophan depletion that are observed in serotonin reuptake inhibitor-treated depressed and obsessive compulsive disorder patients.

Adult↗
PubMed1997

Addition of desipramine to serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to determine whether combined treatment with a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor, desipramine, effectively reduces obsessive-compulsive symptoms in patients who do not respond to SSRIs. METHOD: In a double-blind study, desipramine or placebo was added for 6 or 10 weeks to the treatment of 30 patients with obsessive-compulsive disorder whose symptoms were refractory to SSRI treatment (fluvoxamine, fluoxetine, or sertraline) alone. RESULTS: There were no significant differences between the adjunctive desipramine and placebo groups in obsessive-compulsive or depressive symptoms. CONCLUSIONS: These data suggest that clomipramine's possibly superior efficacy in the treatment of obsessive-compulsive symptoms may not stem from its capacity to inhibit reuptake of norepinephrine.

1-Naphthylamine↗
PubMed1995

m-Chlorophenylpiperazine in patients with obsessive-compulsive disorder: absence of symptom exacerbation.

Oral administration of the serotonin mixed agonist-antagonist meta-chlorophenylpiperazine (mCPP) at 0.5 mg/kg has been reported to exacerbate symptoms of obsessive-compulsive disorder (OCD). In an attempt to replicate these findings, double-blind behavioral and biochemical measures were obtained in 12 drug-free patients (9 men, 3 women) with OCD who received either oral mCPP (0.5 mg/kg), intravenous (IV) mCPP (0.1 mg/kg over 20 min), or placebo in random order on 3 separate test days. Neither oral nor IV mCPP had significant effects on the severity of OCD symptoms. The magnitude of the mCPP-induced plasma prolactin response and plasma mCPP levels were similar to those values obtained in other published studies in which mCPP exacerbated OCD symptoms. In contrast, both oral and IV mCPP were associated with significant increases in ratings of anxiety. These findings suggest that mCPP, whether administered by an oral or intravenous route (as a slow infusion), may not be a reliable probe for investigating obsessive-compulsive symptoms. It is possible, however, that more reproducible behavioral findings might be obtained by identifying susceptible subgroups of OCD or by including a behavioral exposure condition.

Administration, Oral↗
PubMed1995

Lack of efficacy of clozapine monotherapy in refractory obsessive-compulsive disorder.

OBJECTIVE: The authors assessed the efficacy of clozapine monotherapy for adults with treatment-resistant obsessive-compulsive disorder. METHOD: Twelve adults with refractory obsessive-compulsive disorder participated in a 10-week, open-label, systematic trial of clozapine. They were assessed with the Yale-Brown Obsessive Compulsive Scale, the Hamilton Depression Rating Scale, and the global improvement item of the Clinical Global Impression (CGI) scale. RESULTS: None of the 10 patients who completed the trial was a responder. No significant change was observed in obsessive-compulsive or depressive symptoms or in scores on the CGI global improvement item. CONCLUSIONS: These findings suggest that clozapine monotherapy is not effective for most adult patients with treatment-resistant obsessive-compulsive disorder.

Adult↗
PubMed1994

Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors.

METHODS: The effects of short-term tryptophan depletion were examined in 15 patients with DSM-III-R obsessive-compulsive disorder who had demonstrated symptom reduction following treatment with serotonin reuptake inhibitors. Patients received a 24-hour, low-tryptophan (160-mg/d) diet followed the next morning by a drink of 15 amino acids. A double-blind, placebo-controlled cross-over design was used. RESULTS: The diet and the amino acid drink reduced free plasma tryptophan levels by a mean of 84% 5 hours later. Short-term tryptophan depletion did not significantly change mean ratings of obsessions and compulsions. In contrast, mean depression ratings were significantly increased with tryptophan depletion compared with the control (tryptophan-supplemented) testing. CONCLUSION: Maintenance of serotonin reuptake inhibitor-induced improvement of obsessive and compulsive symptoms, unlike remission of depressive symptoms, may not depend on ongoing short-term availability of serotonin.

Adult↗
PubMed1994

Superficial parotidectomy in the treatment of cutaneous melanoma of the head and neck.

The preauricular lymph nodes are frequently the first site of metastatic disease from primary malignant melanoma of the upper two-thirds of the face or the anterior scalp. For these patients, or those with adjacent metastatic nodal disease, the prognosis is poor. The median survival of 13 such patients presented was 2 years, with two long-term survivors at 4 and 6 years. Palliative surgery can, however, prevent uncontrolled locoregional disease. Patients with palpable preauricular and cervical node disease should be treated by facial nerve-preserving parotidectomy and radical neck dissection. When no cervical nodes are palpable in patients with preauricular node metastasis, peroperative jugulodigastric node biopsy and frozen-section histopathological examination are useful to select patients for radical neck dissection.

Adolescent↗
PubMed1994

The role of central oxytocin in obsessive compulsive disorder and related normal behavior.

Oxytocin (OT) is a neurosecretory nonapeptide synthesized in hypothalamic cells, which project to widely distributed sites in the CNS as well as the neurohypophysis. Central OT affects a variety of cognitive, grooming, affiliative, sexual, and reproductive behaviors in animals. Obsessive Compulsive Disorder (OCD) includes a range of cognitive and behavioral symptoms that bear some relationship to dimensions of behavior associated with OT. Anecdotal data and a recently completed cerebrospinal fluid (CSF) study provide evidence that some forms of OCD are related to OT dysfunction. Based on these findings, we hypothesize: 1) that some forms of OCD are at the extreme end of a range of normal behaviors that are mediated by OT and related systems; and that 2) some normal cognitive, affiliative, and sexual behaviors contain elements that are similar to features of OCD. Alternative hypotheses are considered, and a series of predictions are presented concerning the relationship between central OT and the onset, course, treatment response, and response to challenge procedures seen in this form of OCD.

Animals↗
PubMed1993

The serotonin hypothesis of obsessive compulsive disorder.

The above studies investigating the responsivity of the 5-HT system to provocation provide some support for the hypothesis drawn from the results of pharmacologic treatment trials and studies of biological markers that dysregulation of the 5-HT system may be involved in the pathogenesis of OC symptoms. While results of several studies document blunting of neuroendocrine responses to 5-HT agonists, only one study suggests a small increase in responsiveness compared to healthy controls. Combined with neurophysiologic data suggesting net increases in 5-HT functioning following treatment with SRIs, these results suggest that the primary deficit in OCD is not one of increased 5-HT responsivity. Exacerbation of OC symptoms sometimes observed during mCPP challenge is not entirely consistent with this hypothesis and additional studies are required to clarify the significance of these findings. However, behavioral hypersensitivity coupled with neuroendocrine hyposensitivity to serotonergic stimulation might characterize the serotonergic dysfunction accompanying OCD. The complexity of the 5-HT system, and the likelihood that behavioral and neuroendocrine responses are mediated by different receptor subtypes makes this hypothesis entirely plausible. The efficacy of SRIs in the treatment of OCD remains the firmest evidence of serotonergic involvement in this condition. Results of challenge studies in OCD also suggest a possible dysregulation in 5-HT function, although the precise nature of this disturbance remains elusive. Neuroendocrine responses to 5-HT agonists generally are consistent with a tendency toward hyposensitivity in OCD. Behavioral results, while more mixed, indicate a hypersensitivity to 5-HT agonists. Further refinement in dependent and independent variables used in challenge studies may clarify remaining questions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Limited therapeutic effect of addition of buspirone in fluvoxamine-refractory obsessive-compulsive disorder.

The authors found that buspirone added to the treatment of 33 patients with obsessive-compulsive disorder who were refractory to the serotonin reuptake inhibitor fluvoxamine was no better than placebo in reducing obsessive-compulsive, depressive, or anxiety symptoms. This finding suggests that addition of buspirone to ongoing fluvoxamine therapy is not an effective treatment strategy for most patients with obsessive-compulsive disorder.

Adult↗
PubMed1993

The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder.

This retrospective case-controlled analysis evaluated treatment response to the serotonin reuptake inhibitor fluvoxamine in patients with obsessive-compulsive disorder (OCD), with or without a comorbid chronic tic disorder. Thirty-three fluvoxamine-treated OCD patients with a concurrent chronic tic disorder were compared with 33 age- and sex-matched OCD patients without chronic tics who had received fluvoxamine treatment in the same setting during the same period of time and in a similar manner. Although both groups of patients demonstrated statistically significant reductions in obsessive-compulsive, depressive, and anxiety symptoms with fluvoxamine treatment, the frequency and magnitude of response of obsessive-compulsive symptoms was significantly different between the two groups. A clinically meaningful improvement in obsessive-compulsive symptoms occurred in only 21% of OCD patients with comorbid chronic tics compared with a 52% response rate in OCD patients without chronic tics. Moreover, OCD patients with a concurrent chronic tic disorder showed only a 17% reduction in Yale-Brown Obsessive-Compulsive Scale scores compared with a 32% decrease in the severity of obsessive-compulsive symptoms in those OCD patients without chronic tics. These results suggest that serotonin reuptake inhibitor monotherapy may be less efficacious for improving obsessive-compulsive symptoms in OCD patients with than without tics. Combined with differences in the clinical phenomenology between these two groups, these treatment response data support the hypothesis that OCD patients with a comorbid chronic tic disorder may be a clinically meaningful subtype.

Adult↗
PubMed1993

Biological approaches to treatment-resistant obsessive compulsive disorder.

Biological approaches to the patient with treatment-resistant obsessive compulsive disorder are briefly reviewed. The most commonly employed strategy involves combining a potent serotonin reuptake inhibitor (SRI) (e.g., clomipramine or fluvoxamine) with another medication that may exert effects on the brain serotonin system. Open-label reports regarding the addition of tryptophan, fenfluramine, lithium, or buspirone to ongoing SRI therapy of obsessive compulsive disorder are encouraging. However, the anti-obsessive compulsive efficacy of SRI-lithium and SRI-buspirone combination therapy has not been confirmed in recent controlled trials. Preliminary evidence suggests that addition of neuroleptic may benefit SRI-refractory obsessive compulsive disorder patients who have a comorbid chronic tic disorder. Other biological approaches (e.g., electroconvulsive therapy and psychosurgery) are considered in terms of their narrowly defined roles in the treatment of patients with SRI-resistant obsessive compulsive disorder. Finally, an algorithm is proposed for those patients with obsessive compulsive disorder who fail to respond to an adequate trial with a potent SRI.

Behavior Therapy↗
PubMed1992

Metastasectomy.

The literature on metastasectomy abounds in anecdote and retrospective studies of non-randomized patients. In this paper, the published evidence concerning the efficacy of metastasectomy in the lung, liver, brain, gastrointestinal tract and omentum is reviewed to formulate practical recommendations for patient selection and treatment. At some sites metastasectomy can be recommended with little hesitation for more widespread application, but surgery for liver metastases should still be regarded with some reservation.

Adult↗