ABSTRACT
Cognition enhancing drugs often target the dopaminergic system, which is involved in learning and memory, including working memory that in turn involves mainly the prefrontal cortex and the hippocampus. In most animal models for modulations of working memory animals are pre-trained to a certain criterion and treated then acutely to test drugs effects on working memory. Thus, little is known regarding subchronic or chronic application of cognition enhancing drugs and working memory performance. Therefore we trained male rats over six days in a rewarded alternation test in a T-maze. Rats received daily injections of either modafinil or Levodopa (L-Dopa) at a lower and a higher dose 30min before training. Levodopa but not modafinil increased working memory performance during early training significantly at day 3 when compared to vehicle controls. Both drugs induced dose dependent differences in working memory with significantly better performance at low doses compared to high doses for modafinil, in contrast to L-Dopa where high dose treated rats performed better than low dose rats. Strikingly, these effects appeared only at day 3 for both drugs, followed by a decline in behavioral performance. Thus, a critical drug independent time window for dopaminergic effects upon working memory could be revealed. Evaluating the underlying mechanisms contributes to the understanding of temporal effects of dopamine on working memory performance.
Subject(s)
Benzhydryl Compounds/administration & dosage , Dopamine Agents/administration & dosage , Levodopa/administration & dosage , Memory, Short-Term/drug effects , Spatial Memory/drug effects , Animals , Dose-Response Relationship, Drug , Male , Modafinil , Rats , Rats, Sprague-DawleyABSTRACT
We report a case of patient presenting with a very large pulmonary metastasis which revealed a previously unrecognised uterine epithelioid leiomyosarcoma. This is a rare tumour with a poor prognosis. The treatment of both the primary tumour and the metastasis was surgical.
Subject(s)
Leiomyosarcoma/secondary , Lung Neoplasms/secondary , Uterine Neoplasms/pathology , Female , Follow-Up Studies , Humans , Hysterectomy , Leiomyosarcoma/pathology , Leiomyosarcoma/surgery , Lung Neoplasms/surgery , Middle Aged , Pneumonectomy , Uterine Neoplasms/surgeryABSTRACT
In 164 patients with Hodgkin's disease staged between 1973 and 1979 the response to the 3 initial cycles of multiagent chemotherapy was evaluated as a prognosticator of survival. Treatment of localized disease (Stages I, II, III1) consisted of 3 cycles of chemotherapy followed by subtotal nodal irradiation, including the splenic area in non splenectomized patients. Treatment of extended disease (Stage III2 and IV) consisted of 6 cycles followed by low-dosage radiotherapy of initial bulky disease. Five-year actuarial survival was 88% in Stage I, 80% in II, 100% in III1, 45% in III2 and IV. Chemotherapy-induced complete remission after 3 cycles (CH leads to CR) was associated with a favorable prognosis. Five-year survival of Stage III2 and IV patients was better in those who reached CH leads to CR than in those who did not (75% versus 25%; P less than 0.01). This relationship between CH leads to CR and five-year survival was confirmed in patients with localized disease, as shown in Stage II patients (respectively 97% versus 63%; P less than 0.05). Therefore the response to initial chemotherapy provides a new prognostic factor that may serve to delineate a "high-risk" group of patients. The latter deserve aggressive therapy while those in the favorable group would benefit from a less aggressive combined regimen that would minimize long-term complications.
