Conformationally restricted analogues of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide

Conformationally restricted analogues of the selective partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5; 2) were synthesized. The compounds were tested for muscarinic and antimuscarinic activity in the isolated guinea pig ileum and in intact mice. They were found to be moderately potent muscarinic antagonists or weak partial agonists. The new compounds were less potent than 2 in inhibiting (-)-[3H]-N-methylscopolamine binding in the rate cerebral cortex. Thus, structural modifications of 2 in which part of the amide moiety has been connected with the methyl group in the butynyl chain to form a five-membered ring decrease affinity and in most cases abolish efficacy.     

A correctable complication of advanced congestive heart failure

Hyponatremia is a common complication of chronic advanced CHF unresponsive to the usual therapeutic measures. Thus low levels of serum sodium are a significant marker for severe CHF refractory to the more conventional measures. The combined use of ACE inhibitors and diuretics is generally very effective in correcting the hyponatremic state and often helpful in reversing CHF.     

Renal magnesium wasting in two families with autosomal dominant inheritance

Hypomagnesemia due to isolated renal magnesium loss was demonstrated in two unrelated families with autosomal dominant mode of inheritance. Magnesium infusions performed in two patients showed not only a reduced renal magnesium threshold but also a lowered renal tubular maximum for magnesium. All members of both families who presented with hypomagnesemia had also a lowered excretion of calcium in the urine, presumably as a consequence of increased reabsorption in Henle's loop.     

Comparative study of long-term effects of surgical excision and excision combined with radiotherapy or chemotherapy in breast cancer: an analysis of 192 cases

Clinical data of 192 patients with breast cancer with a primary lesion of 2-5 cm (stage II according to the criteria recommended by the UICC) and with histopathologically confirmed positive axillary lymph nodes were analyzed. The patients were divided into three groups: 1) surgical excision alone; 2) surgery plus irradiation; and 3) surgery plus chemotherapy. It was shown that the 5-year survival rates for these groups were 40.5%, 61.0%, and 62.0%, respectively (P less than .05).     

The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy

The use of adjuvant radiation therapy in breast cancer patients treated with mastectomy and adjuvant chemotherapy has been controversial. In order to assess the necessity and effectiveness of adjuvant radiation therapy in this setting, we reviewed the results in 510 patients with T1-T3 tumors and pathologically positive nodes or tumors larger than 5 cm and negative nodes who were treated with adjuvant chemotherapy. Patients with four or more positive nodes or at least one positive apical node were randomized to receive either five or ten cycles of cyclophosphamide/Adriamycin (Adria Laboratories, Columbus, OH) (CA) and patients with one to three positive nodes or operable tumors larger than 5 cm and pathologically negative nodes were randomized to receive eight cycles of either cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) or methotrexate and 5-FU (MF) chemotherapy. Two hundred six of these patients were subsequently rerandomized to receive either no further treatment or adjuvant radiotherapy. Thirty-five patients withdrew after randomization, including 34 who declined to receive radiotherapy. Radiation therapy consisted of 4,500 cGy in 5 weeks to the chest wall and appropriate draining lymph nodes. Median follow-up from chemotherapy randomization is 45 months for patients in the CA arm and 53 months for those in the CMF/MF arm. The crude rate of local failure (chest wall or draining lymph node areas) as first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03). For patients in the CMF/MF arm, the rate of local failure as the first site of failure was nearly the same for patients randomized to chemotherapy only as for those randomized to adjuvant radiotherapy as well (5% v 2%). For patients in the CA arm, the crude rate of local failure was 20% for patients randomized to receive chemotherapy only, and 6% for those randomized to both types of adjuvant treatment (P = .03). Among the 43 patients treated with CA who actually received radiotherapy, there was only one local failure, compared with 12 local failures among the 59 patients (20%) who actually did not receive radiotherapy (P = .007). No significant difference was seen in disease-free survival or overall survival in either the CA or the CMF/MF arm between patients randomized to receive radiation therapy and those randomized to no further treatment.(ABSTRACT TRUNCATED AT 400 WORDS)