Dopamine supports sentence comprehension in Parkinson's Disease.

OBJECTIVE: To determine the role of dopamine in the executive resource component of sentence comprehension. METHODS: We studied sentence-picture matching in 20 right-handed, non-demented, native English speakers with mild Parkinson's disease (PD) when 'on' and 'off' their levodopa, taking into account disease duration to control for endogenous dopamine metabolism. We also administered a verbal working memory measure that does not involve specific grammatical manipulations. RESULTS: PD patients 'off' levodopa demonstrated a significant discrepancy in their comprehension of grammatically complex sentences compared to grammatically simpler sentences that was not evident when PD patients were 'on' levodopa. An error analysis demonstrated that impaired comprehension of grammatically complex sentences when 'off' levodopa was associated with poorer performance on foils requiring working memory resources. Performance on an independent measure of verbal working memory correlated only with comprehension of grammatically complex sentences during levodopa supplementation, but working memory according to this measure did not differ during 'on' and 'off' states. CONCLUSION: Dopamine supports the executive resources contributing to sentence comprehension in PD.

Cognitive resource limitations during sentence comprehension in Parkinson's disease.

Patients with idiopathic Parkinson's disease (PD) were asked to identify the agent of the action in orally presented sentences with subject-relative or object-relative center-embedded clauses while simultaneously performing a secondary task that was less resource-demanding (finger tapping) or more resource-demanding (recognition span). We found that a subgroup of PD patients with impaired sentence comprehension at baseline (no secondary task) did not differ from random in their accuracy understanding all types of sentences during the more demanding (recognition span) condition and also had difficulty understanding the most complex sentences during the less demanding (finger tapping) condition. Control subjects and PD patients without baseline sentence comprehension difficulty were random only in their comprehension of the most complex sentences under the more demanding (recognition span) secondary task condition. Examination of response latencies for accurately understood sentences revealed only an effect for the type of sentence, and this was equally evident across all groups of subjects and regardless of the condition under which the sentences were administered. The sensitivity of PD patients' sentence comprehension accuracy to secondary task resource demands is most consistent with the hypothesis that limited cognitive resources contribute to sentence comprehension difficulty in PD.

The prognostic significance of delayed hypersensitivity to dinitrochlorobenzene and mechlorethamine hydrochloride in cutaneous T cell lymphoma.

Recent studies suggest that cells elaborating type 1 cytokines are important mediators of anti-tumor cell-mediated immunity in cutaneous T cell lymphoma. Type 1 cell-mediated immune responsiveness was assessed in 276 patients with cutaneous T cell lymphoma (mycosis fungoides and Sézary syndrome) using 2,4-dinitrochlorobenzene (DNCB) skin testing as part of the initial evaluation. The overall rate of sensitization after one and two DNCB challenges was 32% and 67%, respectively, which is much decreased compared with the expected rate of more than 95% for normal individuals. Moreover, the frequency of DNCB sensitization and allergic contact dermatitis to topically applied mechlorethamine decreased with advancing stage of disease. In addition to the expected strong correlation with stage, we observed that patients who were DNCB test positive were significantly less likely to experience disease progression and had a better overall prognosis compared with DNCB-negative patients. These results support the concept that cell-mediated responses are important in cutaneous T cell lymphoma, and that augmentation of these responses would be therapeutically beneficial.

Frequent low doses of intravenous mechlorethamine for late-stage mycosis fungoides lymphoma.

Ninety-two courses of daily low-dose intravenous nitrogen mustard were administered to 46 patients with advanced cutaneous lymphomas (mycosis fungoides, Sezary syndrome and lymphoma cutis). Seventy-eight % of patients showed objective clinical remission, and 35% reached a clinically disease-free state following 1 or more courses. The response rate was greater in patients with the plaque-tumor type of mycosis fungoides than in those with erythrodermic variants. Therapy was free of significant side effects.