One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

SUMMARY Reassessment of the 'gastric bactericidal barrier' to enteric bacteria in man included studies of the bactericidal activity of (1) the normal and achlorhydric stomach in vivo and (2) normal and achlorhydric gastric juice and other media in vitro. Within 30 minutes virtually all bacteria (Serratia marcescens) were eliminated in the normal stomach whereas no reduction occurred in the achlorhydric stomach in one hour. In vitro, identical bactericidal activity was observed at the same pH (from 2.0 to 7.0) in normal gastric juice, achlorhydric gastric juice, aqueous HCI, and nutrient broth. At pH less than 4.0, 99.9 % of the bacteria were killed within 30 minutes. The presence of profuse bacterial flora, including coliforms, found in markedly acid-deficient but not in normal stomachs, correlates well with the absence of bactericidal activity. Thus, the 'gastric bactericidal barrier' is primarily pH-hydrochloric acid dependent, with other constituents of gastric juice contributing little, if any, detectable effect on the destruction of microorganisms.A relationship between gastric acid secretion and bacterial diarrhoeas has been suspected for the past 100 years since enteric bacteria do not survive in an acidic environment (Bartle and Harkins, 1925;Garrod, 1939). Furthermore, gastric bactericidal factors, in addition to acid, have been postulated (Gregersen, 1916;Scheer, 1919;Knott, 1923;Goldsworthy and Florey, 1930;Sebastianelli, 1937;Garrod, 1939;Thompson, 1940;Balazs, 1962). In the latter part of the 19th and early 20th centuries, Hewetson (1904), Knott (1923), Arnold (1927), Camps (1933, Hurst (1934), Garrod (1939, and others (Gregersen, 1916;Scheer, 1919;Bartle and Harkins, 1925;Sebastianelli, 1937) believed that patients with reduced or absent gastric acid secretion were more susceptible to bacterial dysenteries and enunciated the concept of the 'gastric bactericidal barrier' (Hewetson, 1904;Gregersen, 1916;Scheer, 1919;Knott, 1923;Bartle and Harkins, 1925;Arnold, 1927;Camps, 1933;Hurst, 1934;Teale, 1934;Sebastianelli, 1937;Garrod, 1939). Today, despite a century of study, the relationship of gastric acidity to the pathogenesis of enteric infec-'Please address reprint requests to Dr Norman Zamcheck, Mallory Gastrointestinal Laboratory, Boston City Hospital, Boston, Mass. 02118.Received for publication 16 December 1971. tions and the particular relevance of gastric anacidity in this regard are still insufficiently appreciated.It is the purpose of this paper (a) to reassess the bactericidal activity of the normal and achlorhydric stomach and of normal and achlorhydric gastric juice; (b) to enumerate the bacterial flora of the normal and acid-deficient stomach; and (c) to update the clinical relevance of the 'gastric bactericidal barrier' in the light of these findings and those of other workers. Materials and Methods PATIENTSThree groups were studied: (1)

Summary. The administration of a carbohydrate-containing diet for 24 hours to rats previously fasted for 3 days led to a twofold increase in total intestinal sucrase and sucrase specific activity. The specific activity of maltase was similarly increased, but lactase activity was unaffected. The sucrose-containing diet led to a greater increase in sucrase than maltase activity, whereas the converse was true of the maltose-containing diet. A carbohydrate-free isocaloric diet led to a slight increase in the total intestinal sucrase, but sucrase specific activity was unchanged. Assay of sucrase activity of mixed homogenates from casein-fed and sucrose-fed rats or fasted and sucrose-fed animals yielded activities that were additive. The Michaelis constant (Km) of the enzyme hydrolyzing sucrose was similar in the fasted, casein-fed, and sucrose-fed rats. The maximal velocity (Vmax) was twice greater in sucrose-fed as compared to casein-fed or fasted rats, suggesting an increased quantity of enzyme subsequent to sucrose feeding.Adrenalectomized rats maintained on 1.0% salt intake had sucrase and maltase levels comparable to those of controls. Steroid administration did not significantly increase their activities. The response to sucrose feeding was similar in both control and adrenalectomized rats, indicative of the absence of steroidal control on sucrase and maltase activity in the adult animal.Studies using intestinal ring preparations indicated that sucrose hydrolysis by the intact cells proceeded more rapidly when animals were fed sucrose. Additional corroboration of the physiologic significance of the increased enzyme levels in homogenates was afforded by intestinal perfusion studies. Sucrose hydrolysis increased twofold and fructose absorption fourfold in animals fed sucrose when compared to either fasted or casein-fed rats.

No abstract