Achalasia in a father and son.

Two cases of achalasia are described in a father and son. This is only the second such occurrence reported. A review of the literature is presented supporting the possibility of transmission via autosomal recessive inheritance.

Modification of the breath hydrogen test: increased sensitivity for the detection of carbohydrate malabsorption.

The pulmonary excretion of hydrogen after a carbohydrate meal has been used to diagnose carbohydrate malabsorption in the small intestine In this study, the protocol for performing breath tests has been modified by the addition of a prolonged carbohydrate-free preparation (greater than 15 hr) and the administration of the test sugar in a defined formula containing protein and fat. The carbohydrate-free preparation significantly decreased baseline H2 excretion, implying that elevations in baseline H2 concentrations are related to carbohydrate malabsorption occurring on the night preceding the breath test. The excretion of H2 after carbohydrate meals was prolonged (greater than 8 hr), with the majority of H2 excreted more than 4 hr after the meal. The time course of H2 excretion was similar in all subjects tested and was independent of the dose and type of sugar used. When H2 excretion between 4 and 7 hr after the meal was analyzed, all subjects taking at least 3 gm of lactulose excreted significant H2 as compared to those taking carbohydrate-free meals. The addition of 10 gm of lactulose to the standard preparation on the night preceding a breath test caused a leftward shift in the time curve of H2 excretion after a subsequent 10 gm lactulose meal, indicating earlier H2 production in the colon. These results imply that breath testing can be used to determine the capacity for intestinal sugar absorption in humans and demonstrate that prior sugar malabsorption may affect the breath H2 response to a meal.

Regulation of rat proximal intestinal glycolytic enzyme activity by ileal perfusion with glucose.

Specific activities of the glycolytic enzymes fructose-1-phosphate aldolase, fructose-1,6-diphophate aldolase, and pyruvate kinase, are higher in rat duodenum and jejunum than in ileum. Whether this gradient reflects the failure of dietary sugars to reach the ileum in high concentrations is unknown. Rats were first fed a carbohydrate-free diet for 3 days, which virtually removed the proximal-distal gradient of enzyme specific activities. Twenty percent glucose was then perfused directly into either the duodenum or the ileum for 3 days. Both proximal and distal glucose perfusion restored the normal gradient of all three enzymes. Ileal pyruvate kinase was also increased by ileal glucose perfusion, but ileal aldolases were no higher after distal perfusion than after duodenal perfusion. The low ileal aldolase levels normally found in fed rats therefore are an intrinsic property of distal intestine and are not due to failure of dietary sugar to reach this portion of the gut. Furthermore, adaptation of duodenal and jejunal glycolytic enzymes to ileal glucose perfusion suggests a humoral and/or neural mechanism rather than a direct local luminal effect of the sugar itself.

Effects of insulin, tolbutamide, and glucagon on activities of jejunal carbohydrate-metabolizing enzymes in humans.

The activities of jejunal carbohydrate-metabolizing enzymes show adaptive drugs, and sex hormones. To learn whether insulin, tolbutamide, and glucagon had effects on these enzymes, we performed serial peroral jejunal biopsies in normal young men and in obese patients, before and after treatment with these agents. Jejunal mucosa was assayed for glycolytic enzyme activities, pyruvate kinase (PK), hexokinase (HK), and fructose-1,6-diphosphate aldolase (FDPA), and the nonglycolytic enzyme activity, fructose diphosphatase (FDPase). Insulin significantly increased the activity of jejunal PK (+48% change from control) and HK (+6%), decreased the activity of FDPase (-36%),and had no effect on FDPA. Glucagon had opposite effects; the activity of PK was decreased (-33%) and FDPase was increased (+50%). Tolbutamide significantly increased the activities of PK (+47%), HK (+14%), and FDPA (+7%), and decreased the activities of FDPase (-36%). The results of tolbutamide on glycolytic enzyme activities were independent of endogenous insulin. The data support the concept that jejunal carbohydrate-metabolizing enzymes in man respond to hormones and drugs similar to responses observed in rat liver. This is important because it now gives us a means of studying the actions of these hormones directly in human tissue.

Diet and intestinal enzyme adaptation: implications for gastrointestinal disorders.

Recent studies have demonstrated that the human intestinal enzymes of carbohydrate digestion and metabolism can be regulated by dietary sugars. These studies have utilized direct assay of intestinal mucosal enzyme activity. Mucosa has been obtained by the use of peroral jejunal biopsy techniques which provide 10-15 mg of mucosa in a safe, simple and reproducible manner. Dietary sucrose, as compared to dietary glucose, increases the activities of the jejunal disaccharidases, sucrase and maltase, but not lactase. Fructose reproduces the sucrose effect and appears to be the active principle in the sucrose molecule. Lactose deprivation or lactose feeding does not alter lactase activity. Fructose has been useful in treating one patient with sucrase-isomaltase deficiency. Jejunal glycolytic enzyme activities are also regulated by dietary sugars. Certain enzymes are highest with specific dietary carbohydrates, lower with other sugars and lowest on a carbohydrate-free diet. The regulation of human jejunal glycolytic enzyme activity takes place in hours, whereas the change in disaccharidase activity occurs in 2-5 days. The mechanism of this regulation is not known. Additional investigations have shown that jejunal glycolytic enzyme activities but not the disaccharidases are controlled by oral folic acid as well. This effect occurs within 1 day also. The mechanism is unknown. Large doses of folate have been of benefit in a few patients with certain glycolytic enzyme deficiency states. Preliminary studies have demonstrated that selected patients with chronic undiagnosed intestinal disorders fail to manifest an adaptive response of their jejunal glycolytic enzyme activities to dietary sugars. This condition has been termed a "maladaptation syndrome.".

Regional variation in glycolytic enzyme adaptation to dietary sugars in rat small intestine.

This investigation evaluated the adaptive response of the glycolytic enzymes, fructose-1-phosphate aldolase, fructose-1, 6-diphosphate aldolase, and pyruvate kinase, to dietary sugars throughout the small intestine. In addition, the effect of prior diet on this adaptive response and on the enzyme distribution pattern along the small intestine was studied. Rats were fed 40% glucose, 68% sucrose or carbohydrate-free diets for 6 days (baseline diet), followed by one of three isocaloric test diets (40% glucose, 68% sucrose or carbohydrate-free for 3 days. In other groups of tats isocaloric diets of 68% glucose, 68% fructose or 34% glucose + 34% fructose, fed for 4 days, were compared. Enzymes were assayed in the mucosa of the duodenum (D),and in 5 equal (by length) segments from the Ligament of Treitz to the ileocecal valve (J1, J2, J3, I1 and I2). Enzyme specific activities were significantly higher in the proximal (D-J1-J2) than distal segments (J3-I1-I2) on all diets (P smaller than 0.001). Enzyme activities after test diet periods were determined only by the test diet, and were independent of the baseline diet for all segments. The 68% carbohydrate diets increased enzyme activities significantly more (P smaller than 0.001) than the 40% glucose or carbohydrate free diets, in all segments. On the 40% glucose diet, activities were significantly higher (P smaller than 0.05) than on the carbohydrate free diet in D and J1, but not distally. The data suggest that there is an intrinsic gradient of enzyme activity from the proximal to the distal small intestine which persists despite dietary manipulation, and that all segments of the small bowel show adaptive increases to dietary sugars.