A CLINICAL STUDY OF LACTOSE INTOLERANCE AFTER GASTRECTOMY. First Department of Surgery, Kurume University School of Medicine Kurume, 830, Japan
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1 THE KURUME MEDICAL JOURNAL Vol. 25, No. 4, p , 1978 A CLINICAL STUDY OF LACTOSE INTOLERANCE AFTER GASTRECTOMY HIROYOSHI MIZOTE, SHIGEHIRO TERASAKI, TADAHIKO RYU, KOUICHI VEDA, YOSHIMASA IWAMI, TAKAYUKI SASAKI AND TETSUZO INOGUCHI First Department of Surgery, Kurume University School of Medicine Kurume, 830, Japan Received for publication October 14, 1978 We examined 13 cases of developing gastrectomy. The major symtom in these 13 cases was diarrhea developing ingestion of cow's milk. In all cases stool ph was acid and stool clinitest was positive. These symptoms were improved with administration of 0.5 gm. (Galantase) per 180 ml. of cow's milk of 5 to 10 minuts milk intake. INTRODUCTION Lactose is a very important disease in pediatrics, and in cases of severe chronic diarrhea, one must consider it as a possible diagnosis. There have been many studies of this disease in the pediatric field, but clinical study of adult has not been sufficient in our country. Lactose is a kind of disaccharide. When it is taken into the brush border of the mucosa of the small intestine, it is hydrolyzed into two monosaccharides, glucose and ga, and absorbed. When there is a deficiency of lactase, cannot be hydrolyzed. The unhydrolyzed increases the intraintestinal osmotic pressure, which causes water to move into the intestine, resulting in watery diarrhea. In addition, is also fermented by the intestinal flora, producing lactic acid or acetic acid, which makes the stool acid and increases peristalsis, producing diarrhea. In our recent experience, with diarrhea gastrectomy was improved dramatically by administration of lactase. In this paper we will present these cases and discuss the metabolism of before and gastrectomy. STUDY OF HYDROLYSIS OF LACTOSE AFTER GASTRECTOMY 1) Subjects Our subjects were 13 patients with diarrhea gastrectomy and 7 patients who had stomach diseases and underwent gastrectmy without subsequent diarrhea seen in the 9-month period from April 1, 1972 to December 30, (Table I and II). 295
2 296 MIZOTE, ET AL. TABLE Cases of developing gastrectomy I 2) Method Stools were collected with a direct collecting tube. The character of the stool was described as to consistency, color, presence of granules, mucus and blood. Stool ph was measured with Toyo ph test paper. Quantitative measure-
3 GASTRECTOMY LACTOSE INTOLERANCE 297 TABLE Lactose tolerance test before and Gastrectomy II ment of reduced sugars was performed as follows : 1 part stool and 2 parts distilled water were centrifuged for 10 min, at 3,000 rpm. Ten drops of supernatant or a mixture of 5 drops of watery stool and 10 drops of distilled water were reacted with Clinitest (Ames) and measured semiquantitatively. For semiquantitative measurement of glucose, Tes-Tape (Lilly-Shionogi) was used. 50 gm. was mixed with 400 ml. of warm water for the tolerance test and 50 gm gm. Galantase were mixed with warm water for the + lactase tolerance test. These solutions were given orally to the patients, who had fasted for 4 hours. Serial blood samples were taken before treatment, and 30 minutes, 1 hour, 2 hours, and 3 hours treatment. Measurement of blood sugar was done by the glucose oxydase method (Boehringer blood sugar test modified to ultramicro methods ; 20,mil of whole blood was used) and maximum blood glucose rises were examined. 3) Results Clinical data on the 13 cases of gastrectomy are summarized in Table I. In all cases stool ph was acid and stool clinitest was positive. The major symptom in these 13 cases was diarrhea developing ingestion of cow's milk. The character of stools varied from watery diarrhea to loose stool. These symptoms were improved with administration of 0.5 gm. lactase (Galantase) per 180 ml. of cow's
4 MIZOTE, 298 milk 10 to 15 min. milk intake. STUDY OF LACTOSE METABOLISM BEFORE AND AFTER GASTRECTOMY The results of our study of metabolism before and gastrectomy are summarized in Table II and Fig. 1. Lactose tolerance tests produced abdominal symptoms in 5 of 7 cases (70 %) before gastrectomy. A positive Clinitest was seen in 3 cases before gastrectomy. Only in 1 case were neither positive Clinitest nor tolerance test-produced abdominal symptoms seen 2 weeks gastrectomy. This implies that moved rapidly into the small intestine total or subtotal gastrectomy. In + Galantase tolernce tests gastrectomy all the cases except Case 2 showed improved symptoms or no symptoms. Case 2 showed persistent abdominal symptoms and positive Clini- Fig. gastrectomy. 1 Lactose tolerance test ET AL. test. These results showed the effectiveness of lactase (Calantase) in vivo. The elevation of blood sugar in the + Galantase tolerance tests performed surgery showed the effectiveness of this lactase preparation (Fig. 1). In summary, ingested moved rapidly into the small intestine surgery. Lactase in the brush border of the mucosa of the small intestine cannot handle rapidly moved so that appeared surgery even if there were no symptoms before surgery. However when was hydrolyzed into glucose and ga in vitro by lactase and given to the patient, the symptoms were improved. was of DISCUSSION The discovery of congenital by Durand and Holzel and reports on the monosaccharide syndrome by Lindquist and Laplane et al. gave valuable information regarding the physiology of the digestion and absorption of carbohydrates and the etiology and treatment of diarrhea. It is very important from the clinical standpoint that not only the primary disaccharide syndrome and monosaccharide syndrome were found, but also that secondary monoand disaccharide syndromes have been reported in recent years. In 1963 adult cases of were reported by Dahlgvist, Haemmerli and Auricchio. Actual lactase deficiency in the mucosa of the small intestine was verified. The incidence of by race and age is shown in Fig. 2. The absorption rate is good in American and European whites. However
5 GASTRECTOMY LACTOSE INTOLERANCE 299 Fig. 2 Incidence of by race and age ( tolerance test). begins to be seen before 1 year of age among African Negroes and Southeast Asians such as Ugandan's and Thai's. Malabsorption of is seen in 80 to 100 % of the adults in these area. The Japanese shows a middle pattern. The symptoms of adult are abdominal discomfort, abdominal distension, meteorism, abdominal pain and diarrhea associated with ingestion of cow's milk. The patient appears to be healthy without milk intake. Frequently the patient himself cannot recognize this disorder. It has been reported that milk is frequently seen among postgastrectomy patients. However there is a report that lactase activity in these patients is normal and the incidence of lactase deficiency is the same as the control. Sasagawa et a1. reported that lactase deficiency is common among Japanese on the basis that 21.4% of nongastrectomized patients and 10.5% of gastrectomized patients showed blood sugar increases of over 20 mg/dl in tolerance tests. In our study 1 out of 7 nongastrectomized patients showed more than a 20mg/dl elevation of blood sugar in tolerance tests. When gastrojejunostomy is performed in patients who had low lactase activity before surgery and orally administered moves rapidly into the small intestine rather than slowly as under normal conditions, the symptoms of will appear because of the inability of even normal levels of lactase to handle rapidly moved. The diagnosis of can be confirmed by testing the absorption of or by observing diarrhea on loading. For this purpose ph and Clinitests of stools and urine and a subsequent tolerance test are required. Traditionally, the treatment of has consisted of elimination of from the diet or administration of preparations to decrease intestinal peristalsis. However more positive treatment such as administration of lactase with milk or is the treatment of choice in recent years. This lactase preparation (Galantase) is activated at ph and is stable at room temperature for 1 month. In vitro studies on this medicine were performed by Sasagawa 5 gm. of lactase can hydrolyze 92% of 50 gm. of in 15 min. and 100% in 30 min. Studies in vivo showed excellent results, as indicated in Fig. 1. We can now give with this lactase as a source of calories in tube feeding not only for diarrhea but also in patients who need surgery of the upper gastrointestinal tract, especially those with esophageal cancer and cancer of the cardia of the stomach. COMMENT We examined 13 cases of developing gastrectomy in the 9-month period from April 1, 1972 to December 30, We reported
6 300 MIZOTE, ET AL. here the study of the effectiveness of REFERENCES lactase and also studies on the metabolism of before and gastrectomy. DURAND, P. (1958). Lattosuria idiopathica in una pazente con diarrea cronica ed acidosi. Minerva Pediat. 14, HOLZEL, A., SCHWARZ, V. and SUTCLIFFE, K.W. (1959). Defective absorption causing malnutrion in infancy. Lancet, I, Lindquist, B. and MEEUwISSE, G. W. (1962). Chronic diarrhea caused by monosaccharide. Acta Pediat. Scand. 51, LINDQVIST, B., MEEUWISSE, G. W. and MELIN, K. (1962). Glucose ga. Lancet., II, 666. LAPLANE, R. and POLONOVSKI, C. (1962). L' aux sucres a transf ert intestinal acf if. Ses rapports avec l'intorerance au et le syndrome coeliaque. Arch. Franc. Pediat., 19, BURKE, V., KERRY, K. R. and ANDERSON, C. (1965). The relationship of dietary to refractory diarrhea in infancy. Aust. Paediatric. J., 1, ZETTERSTROM, R. and WALDENSTROM, J. (1968). Familial monosaccharide. Mod. Prob. Pediat., 11, , Karger, Basel New York. HARRIS, V. J. and FRANCIS, D. E. M. (1968). Temporaly monosaccharide. Acta Paediat. Scand., 57, DAHLAVIST, A., HAMMOND, J. B., CRANE, R. K., JAMES, P. D., DUNPHY, V. and LITTMAN, A. (1963). Intestinal lactase deficiency and in the adult. Gastroenterol, 45, 48E ) HAEMMERLI, U. P., KISTLER, H., AMMANN, R., MARTHALER, J., SEMENSA, G., AURICCHIO, S. and PRADER,A. (1965). Aqcuired milk in the adult caused by malabsoption due to a selective deficiency of intestinal lactase activity. Amer. J. Med., 38, AURICCHIO, S., RUBINO, A., LANDOLT, M., SEMENZA, G. and PRADER, A. (1963). Isolated intestinal lactase deficiency in the adult. Lancet., II, MCMICHAEL, H., LOND, M. B., WEBB, J. and DAW- SON, A. M. (1965). Lactase deficiency in adults, a case of functional diarrhea. Lancet., I, GRYBOSKI, J., THAYER, W., GABRIELSON, I. and SPIRO, H. M. (1963). Disacchadiuria in gastrointestinal disease. Gastroenterology, 45, WELSH, J. D., OHRER, G. V. and WALKER, A. (1966). Human intestinal disaccharidase activity. Arch. Intern. Med., 117, WEI JERS, H. A. and Van de KAMER, J. H. (1962). Diarrhea caused by deficiency of sugar splitting enzymes II. Acta Paediatrica, 51, HOOFT, C., HANWAERT, J., LAEY, P. and ADRIA- ENSSENS, K. (1963). Intestinal lactase deficiency. Lancet, II, SHEEHY, T. W. and Anderson, P. R. (1965). Disaccharidose activity in normal and diseased small bowel. Lancet, II, 1-4. KERN, F. and STRUTHERS, J. E. (1966). Intestinal lactase deficiency and in adults. J. A. M. A., 195, DRUBS, H. C., HAUSEN, H. T., KLEIN, U.E. and ZIELKE, K. (1967). Uber die Disaccharidasen Aktivitat der Jejunal schleimhaut bei Gesunden and Magenresezierten. Dtsch. Med. Wschr, 92, SASAGAWA, C. (1970). A clinical study of in adults. Diagnosis and Treatment, 58,
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