Na+ transport in normal and CF human bronchial epithelial cells is inhibited by BAY 39-9437.

To test the hypothesis that Na+ transport in human bronchial epithelial (HBE) cells is regulated by a protease-mediated mechanism, we investigated the effects of BAY 39-9437, a recombinant Kunitz-type serine protease inhibitor, on amiloride-sensitive short-circuit current of normal [non-cystic fibrosis (CF) cells] and CF HBE cells. Mucosal treatment of non-CF and CF HBE cells with BAY 39-9437 decreased the short-circuit current, with a half-life of approximately 45 min. At 90 min, BAY 39-9437 (470 nM) reduced Na+ transport by approximately 70%. The inhibitory effect of BAY 39-9437 was concentration dependent, with a half-maximal inhibitory concentration of approximately 25 nM. Na+ transport was restored to control levels, with a half-life of approximately 15 min, on washout of BAY 39-9437. In addition, trypsin (1 microM) rapidly reversed the inhibitory effect of BAY 39-9437. These data indicate that Na+ transport in HBE cells is activated by a BAY 39-9437-inhibitable, endogenously expressed serine protease. BAY 39-9437 inhibition of this serine protease maybe of therapeutic potential for the treatment of Na+ hyperabsorption in CF.

Extrahepatic biliary obstruction associated with pancreatitis.

A total of 40 patients with pancreatitis had associated extrahepatic biliary obstruction. Eighteen had biliary-induced pancreatitis. Comprehensive correction of the biliary tract disease, including cholecystectomy, common duct exploration and, when indicated, transduodenal sphincteroplasty, resulted in a high recovery rate (83%) with no recurrence of pancreatitis. Twenty-two patients had chronic pancreatitis with involvement of the terminal biliary tract by a long tapering stenosis. Nineteen of these patients had chronic fibrocalcific pancreatitis secondary to chronic alcohol abuse. In five patients, the stenosis produced a high grade obstruction which required biliary bypass with choledochoduodenostomy (four) or cholecystoduodenostomy (one). The remaining 14 patients maintained patency of the biliary tract following correction of the underlying pancreatic pathology. The latter consisted of drainage (nine) or resection (five) of 14 associated pseudocysts (present in 64% of the 22 patients), combined with side-to-side pancreaticojejunostomy to decompress an obstruction of the major pancreatic duct. In assessing the degree of terminal bile duct stenosis, calibration of the duct with Bakes dilators or rubber catheters was a useful aid. Two of the 22 patients ultimately proved to have carcinomas, producing obstruction of the pancreatic duct in the head of the gland. Both were treated initially with choledochoduodenostomy. This possibility must be considered in the management of these patients.

Oophorectomy in women with carcinoma of the colon and rectum.

Carcinoma of the colon and rectum metastasizes readily to the ovaries, and oophorectomy during operation upon the colon and rectum remains an effective surgical technique for precluding subsequent oophorectomy and, thereby, diminishing the morbidity of carcinoma of the colon and rectum in women. This procedure does not significantly affect the survival rate. Carcinoma of the ovary has become the fourth most common lethal cancer in women. Usually, the tumor is diagnosed after the development of ascites, mass and weight loss. The five year survival rate remains about 30 per cent. The incidence of carcinoma of the ovary in women with carcinoma of the colon and rectum is roughly five times the incidence of carcinoma of the ovary, that would be expected by chance. We believe the aforementioned observations strongly expand and reinforce the original proponents of prophylactic oophorectomy performed upon women with carcinoma of the colon and rectum and that, therefore, oophorectomy should be an integral part of operation upon the colon and rectum in women.