Search PubMed⌕ Search

Biomedical subjects

R Kurlan

Publications and source records attributed to R Kurlan.

At least 73 records · Page 4Linked to original sources
PubMed1992

The pathogenesis of Tourette's syndrome. A possible role for hormonal and excitatory neurotransmitter influences in brain development.

Tourette's syndrome (TS) is associated with prominent gender differences in clinical expression, tics with a sexual content, and a stabilization or improvement of symptoms after puberty. It is herein hypothesized that some tics can be viewed as inappropriately expressed (normally inhibited) fragments of primitive motor and vocal programs involved in reproductive activity. The brain regions involved in TS (basal ganglia and limbic system) are proposed to be counterparts in humans of those functioning in primitive reproductive behavior whose development and organization are under sex hormone control. It is further hypothesized that sex hormone action is mediated by excitatory neurotransmitter mechanisms such that an excessive trophic effect occurs early in development and a neurotoxic environment emerges later on. The defective gene in TS is hypothesized to influence these developmental processes. This hypothesis has implications for the investigation of the pathogenesis of TS and for experimental therapeutics of the disorder.

Amino Acids↗
PubMed1992

Preliminary examination of the comorbidity of anxiety and depression in Parkinson's disease.

Significant anxiety in combination with depression may represent a specific depressive subtype in Parkinson's disease (PD). To ascertain the prevalence of this symptom complex, we administered a self-report survey and standardized psychological tests that measure anxiety and depression to 164 PD patients and 150 age-matched healthy spouse control subjects. The reporting of depression in combination with panic/anxiety best differentiated the two populations (38% vs. 8%). Depression and anxiety were highly correlated in relationship to clinical features of PD. Our findings suggest that clinically significant levels of depression and anxiety may frequently coexist in PD. The specific neuropathology of PD may predispose to this pattern of behavioral disturbance.

Aged↗
PubMed1991

The time course and magnitude of spontaneous recovery of parkinsonism produced by intracarotid administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to monkeys.

We studied rhesus monkeys with hemiparkinsonism or bilateral parkinsonism produced by unilateral or bilateral intracarotid administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Using a standardized clinical rating scale, 4 hemiparkinsonian monkeys showed a 13 to 56% (mean, 36%) spontaneous improvement during an observation period of up to 25 weeks. Generally, recovery leveled off after 14 weeks. Four bilaterally parkinsonian monkeys showed a 5 to 42% (mean, 22%) improvement over a period of up to 30 weeks. Our findings emphasize that spontaneous recovery is a potentially confounding characteristic of this monkey model when used for assessing novel antiparkinsonian therapies.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

A controlled trial of propoxyphene and naltrexone in patients with Tourette's syndrome.

To investigate the effect of drugs acting on the endogenous opioid system, we studied 10 adults with Tourette's syndrome who received propoxyphene hydrochloride (260 mg/day), naltrexone hydrochloride (50 mg/day), and placebo in a double-blinded, randomized clinical trial. Using a self-report scale (Tourette's Syndrome Symptom List), subjects noted a significant (p less than 0.04) lessening of tics after treatment with naltrexone when compared with placebo. An improvement in performance on the Trail Making B test, a measure of attention and visuomotor sequencing and planning, occurred after receiving naltrexone when compared with placebo (p less than 0.08) or propoxyphene (p less than 0.02). The Trail Making B test best discriminated the treatments (p less than 0.02, analysis of variance). No other treatment effects were observed for several other measures of tic severity, attentional ability, or obsessive-compulsive symptoms. Our findings indicate that pharmacological manipulation of the endogenous opioid system does influence symptoms of Tourette's syndrome.

Adult↗
PubMed1991

The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys.

Abnormally increased subthalamic nucleus output to the internal pallidal segment and the reticular part of the substantia nigra plays a critical pathophysiological role in the development of parkinsonism. Because synaptic transmission of subthalamic output is glutamatergic and mediated, in part, by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptor, AMPA receptor antagonists may possess antiparkinsonian properties. We report that in monoamine-depleted rats, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) (Novo-Nordisk, Copenhagen, Denmark)--a selective antagonist of the AMPA subtype of glutamate receptor--suppressed muscular rigidity but had no effect on akinesia. NBQX microinjected into the subthalamic nucleus, internal pallidal segment, and reticular part of the substantia nigra, but not into the laterodorsal neostriatum of the rats, stimulated locomotor activity and reduced muscular rigidity. In aged Rhesus monkeys with bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, intramuscular NBQX produced clinically apparent improvement in akinesia, tremor, posture, and gross motor skills. NBQX also potentiated the antiparkinsonian effects of L-3,4-dihydroxyphenylalanine in both rats and monkeys. Blockade of excitatory synaptic transmission by AMPA receptor antagonists may provide a new therapeutic strategy for Parkinson's disease (PD).

Animals↗
PubMed1991

Oral levodopa dose-response study in MPTP-induced hemiparkinsonian monkeys: assessment with a new rating scale for monkey parkinsonism.

Quantitative measures for the severity of MPTP-induced parkinsonism and response to antiparkinsonian interventions in monkeys have been lacking. We carried out an oral levodopa dose-response study in two rhesus monkeys whose left hemiparkinsonism was induced by intracarotid administration of MPTP. A newly developed clinical rating scale of monkey parkinsonism showed a consistent dose-response relationship for levodopa over the dosage range of 50-3,500 mg/day. Antiparkinsonian effects appeared at 200 mg/day and were optimal at 1,000-2,000 mg/day. Levodopa also reversed rotational behavior, improved movement times for both the impaired and opposite upper limb, and produced dyskinesias at high dosages. Thus, MPTP-induced hemiparkinsonism in monkeys closely resembles the human disease condition, is associated with sensitive response measures, and should prove valuable for assessing novel antiparkinsonian therapies.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

An open-label trial of fluoxetine for obsessive-compulsive disorder in Gilles de la Tourette's syndrome.

Obsessive-compulsive disorder (OCD) occurs commonly in association with Gilles de la Tourette's syndrome (GTS) and can be a major source of disability. Fluoxetine, a new antidepressant, has been effective for psychiatric patients with OCD. We conducted an open-label trial of fluoxetine (20 to 40 mg/d) for 32 GTS patients with OCD. After 1 week of treatment, six patients (16%) withdrew from the trial due to perceived lack of benefit. Data were analyzed for 26 patients (13 children and 13 adults) who were treated by a neurologist for 3 to 8 months. Following treatment, there was a significant reduction in scores on the Leyton Obsessional Inventory for both the adult and child groups, and 81% of patients reported a subjective improvement in obsessions and compulsions. Since fluoxetine was well tolerated, our findings indicate that the drug may be an effective agent for the treatment of OCD in GTS patients.

Adolescent↗
PubMed1991

Progress in the search for genetic linkage with Tourette syndrome: an exclusion map covering more than 50% of the autosomal genome.

Gilles de la Tourette syndrome is a neuropsychiatric disorder with an autosomal dominant mode of inheritance and reduced penetrance at a single genetic locus. Several research groups have genetic linkage studies underway to detect the chromosomal location of the gene that predisposes for this disorder. Strong and clear evidence of linkage has not yet been produced for Tourette syndrome. This paper presents an overview of the methods and progress of the groups centered at Yale University and Erasmus University in excluding linkage from a large portion of the genome. Our labs have screened 228 genetic marker loci for linkage with a gene for this disorder in a series of affected families in the United States, Canada, The Netherlands, and Norway. More than 50% (and perhaps as much as 66%) of the autosomal genome has now been excluded on the assumption that genetic heterogeneity is not an important factor in the Tourette syndrome pedigrees pooled for this summary.

Chromosome Mapping↗
PubMed1990

Gilles de la Tourette syndrome is not linked to D2-dopamine receptor.

Gilles de la Tourette syndrome has an important genetic component; the pathophysiology of this disorder may involve the dopamine system. We tested a D2-dopamine receptor (locus DRD2, recognized by probe hD2G1) for genetic linkage with Gilles de la Tourette syndrome. Using a genetic linkage map of the region of DRD2 on the long arm of chromosome 11 and restriction fragment length polymorphism data from a total of four markers (DRD2 itself, D11S84, D11S29, and PBGD), we were able to exclude linkage of this candidate gene and Gilles de la Tourette syndrome in two extended kindreds segregating for Gilles de la Tourette syndrome. This rules out causation of Gilles de la Tourette syndrome by mutation in DRD2 in the kindreds studied under the genetic assumptions we employed; use of the map and multipoint linkage analyses also allowed us to exclude a Gilles de la Tourette syndrome susceptibility locus from a larger genetic region.

Chromosome Mapping↗
PubMed1990

Neurosurgical treatment of severe obsessive-compulsive disorder associated with Tourette's syndrome.

We describe two patients with Gilles de la Tourette's syndrome (TS) and disabling obsessive-compulsive and ritualistic behaviors who underwent bilateral radiofrequency anterior cingulotomy. Both achieved a limited but sustained improvement in behavioral symptoms and overall functional abilities. Our observations indicate involvement of limbic structures in this disorder. The procedure should be considered for patients with TS complicated by resistant obsessive-compulsive disorder.

Adult↗
PubMed1990

Segregation and linkage analyses of Tourette's syndrome and related disorders.

Segregation and linkage analyses were performed with data from a large Tourette's syndrome (TS) multigenerational kindred. Results of segregation analyses were remarkably similar to some reported earlier and suggest that the mode of transmission is consistent with autosomal dominant inheritance. The analyses were done using three diagnostic schemes to specify affected family members (TS only; TS or chronic tics [CT]; and TS, CT or obsessive compulsive disorder [OCD]). The estimates of penetrance for the genotypes AA, Aa and aa (A denotes the susceptibility allele) in the analyses including relatives with TS, CT or OCD were 0.99, 0.99 and 0.00, respectively, for males and 0.70, 0.70 and 0.00 for females. Pairwise linkage analyses with 140 marker loci failed to identify a linked marker. However, approximately 30 percent of the genome was excluded as the site of the hypothesized locus for TS.

Child↗
PubMed1989

Carbamazepine-induced tics.

Although a variety of dyskinesias are known to develop during anticonvulsant therapy, carbamazepine-induced tics are rarely recognized. We report three patients with an underlying movement disorder (Huntington's disease, tardive dyskinesia, and Tourette's syndrome) who experienced the onset or exacerbation of tics after the introduction of carbamazepine. These cases confirm the phenomenon of carbamazepine-induced tics and suggest that basal ganglia neuropathology may be an important predisposing factor. The dopaminergic effects of carbamazepine may be responsible for the induction of tics.

Adolescent↗