Delta-frequency stimulation of cerebellar projections can compensate for schizophrenia-related medial frontal dysfunction.

Schizophrenia involves abnormalities in the medial frontal cortex that lead to cognitive deficits. Here we investigate a novel strategy to normalize medial frontal brain activity by stimulating cerebellar projections. We used an interval timing task to study elementary cognitive processing that requires both frontal and cerebellar networks that are disrupted in patients with schizophrenia. We report three novel findings. First, patients with schizophrenia had dysfunctional delta rhythms between 1-4 Hz in the medial frontal cortex. We explored cerebellar-frontal interactions in animal models and found that both frontal and cerebellar neurons were modulated during interval timing and had delta-frequency interactions. Finally, delta-frequency optogenetic stimulation of thalamic synaptic terminals of lateral cerebellar projection neurons rescued timing performance as well as medial frontal activity in a rodent model of schizophrenia-related frontal dysfunction. These data provide insight into how the cerebellum influences medial frontal networks and the role of the cerebellum in cognitive processing.

Evaluation of selected life-skill modules from the contemporary health series with students in grade.

The purpose of the study was to assess the effects over a school term of selected life-skill modules from The Contemporary Health Series-Into Adolescence on scores for self-esteem, health (drug) attitudes, and behaviors of sixth-grade students. The 328 students were from classrooms assigned to either-experimental or control conditions. Analysis indicated that students exposed to selected modules from the curriculum series reported positive changes on a number of health-related variables in the questionnaire.

Radiation therapy for ureteral metastases from breast carcinoma.

Seven breast cancer patients received supervoltage radiation therapy in the Department of Radiation Medicine, Massachusetts General Hospital from 1970--1978 for ureteral-periureteral metastases. Urinary symptoms (flank pain, urgency, hematuria) disappeared completely and permanently for four of five patients; abnormal pyelograms returned completely to normal for three of three; and abnormal renal function tests for two of two. Six of seven patients survived at least one year after irradiation. Indications for irradiation, dose, and techniques are discussed.

5-drug adjuvant chemotherapy for breast cancer.

A series of 41 patients at the MGH who received 5-drug chemotherapy, cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisone, (CMF VP) as adjuvant to surgical treatment of operable breast cancer with 4 or more positive axillary nodes is compared to an analogous group of patients treated with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) reported by Bonadonna et al. in an effort to assess the contribution of the treatment program to disease control. The MGH pattern of disease free survival closely parallels that of Bonadonna. Median disease-free survival among the 24 patients who have not recurred is 27 months; among those who recurred 18 months. The analogous medians for treated patients in the Bonadonna study are 24 months and 16 months, as compared to 27 months and 8 months for his nontreated controls. The treatment program, carried out over a two year period, was well tolerated with excellent patient compliance. There was no significant impact, however, in the disease-free survival of postmenopausal patients. While use of this regimen improved disease-free survival in premenopausal individuals, it is clear that a great deal of room for improvement exists, and newer regimens should be investigated.

Diethylstilbestrol: recommended dosages for different categories of breast cancer patients. Report of the Cooperative Breast Cancer Group.

A total of 523 postmenopausal breast cancer patients with progressive disease were entered in a radomized, double-blind study of four dosages of diethylstibestrol (DES): 1.5, 15, 150, OR 1,500 MG/DAY. Higher dosages produced significantly (p less than .05) higher regression rates: 21% for the 1,500 mg dosage, 17% for the 150 mg dosage, 15% for the 15 mg dosage, and 10% for 1.5 mg dosage. Durations of regressions were similar regardless of the dosages used to induce them. Although the highest dosage produced the highest regression rate overall, selecting the best dosage or treatment of choice for each type of patient based on menopausal age and on dominant metastatic site would result in more regressions.

Combined androgen and antimetabolite therapy of advanced female breast cancer. A report of the cooperative breast cancer group.

A clinical trial of androgen and antimetabolite therapy of advanced female breast cancer was conducted in 110 patients by the Cooperative Breast Cancer Group. An objective regression rate of 20% was achieved in women receiving oral testolactone, 6% in patients given intravenous fluorouracil alone, and 14% when the androgen and antimetabolite were administered together. This randomized trial according to the CBCG protocol did not produce the high regression rate noted previously in a nonrandomized, nonprotocol evaluation of these drugs.