CASE REPORT INTESTINAL LYMPHANGIECTASIA IN A DOG M. MILSTEIN AND S. E. SANFORD* Introduction Several laboratory tests were done in an Intestinal lymphangiectasia is a pathological attempt to identify the organs and disease prodilation of the intestinal lymphatics accom- cesses involved in the diarrhea (Tables I and panied by enteric protein loss, hypoproteinemia II). and lymphocytopenia and manifested clinically On days 1 and 2 of hospitalization the total by edema and/or ascites, diarrhea, steatorrhea white blood cell counts were 7,000 and 5,700 and signs of malabsorption (17). It has been with lymphocyte values of 1,700 and 1,500/ recognized as a clinical entity in humans since mm3 (Table I). 1961 (17) and has been described in dogs Serum glutamic pyruvic transaminase (SGPT) more recently (2, 4, 12). The purpose of this and serum bilirubin levels were within normal report is to describe a case of intestinal lym- limits, as were the concentrations of serum phangiectasia in a dog in which intractable sodium, potassium, chloride and calcium (Table diarrhea was the only manifestation of the II). The total serum protein concentration was condition. normal (7.1 g%) as were the concentrations of albumin and globulin (2.7 and 4.4 g% reHistory spectively). A six year old unilateral cryptorchid German Fecal trypsin was present in the two samShepherd dog with a ten month history of ples tested. Fecal fat, demonstrated with diarrhea was referred to the Small Animal Sudan III stain, was minimal. E. coli was reClinic of the Ontario Veterinary College covered from culture of the feces. No Salmo(OVC) for examination. The owner reported nellae were present. Intestinal parasite eggs that the dog suffered from abnormally fre- were not detected by flotation procedures nor quent bowel movements characterized by a were Giardia organisms present on fresh fecal pale, soft stool. For the last six of the ten smears. Serum d-xylose concentration as demonths, the dog steadily lost weight in spite termined by the method of Hill et al (8) was of a good appetite and increased food con- within normal limits, reaching a maximum of sumption. The dog remained bright and lively. 58 mg% at 60 minutes. No protein was detected Treatment with antispasmodics, antibiotics and in the urine. diet changes, including a two week trial of a Plain abdominal radiographs failed to reveal commercial "intestinal diet", produced no sig- any abnormal findings other than splenomegaly. nificant improvement. Escherichia coli were A barium contrast study of the intestinal tract cultured from the feces. No evidence of inter- was done and patchy, uneven, filling of the nal parasites was detected on microscopic ex- intestinal loops was a prominent feature. amination of the feces. In view of the normal values for the tests reflecting pancreatic, liver and biliary integrity, Clinical Findings the small intestine was considered to be the At the time of presentation the dog was source of the diarrhea. Villus filling diseases, thin, but reasonably hydrated and lively. lymphangiectasia and lymphosarcoma were Neither edema nor ascites was evident on the tentative diagnoses proposed. physical examination. Body temperature was Accordingly, an exploratory laparotomy was 39.2°C, pulse was 72 beats per minute, body done. The intestines were found to be flaccid weight was 31.5 kg, and heart and lung sounds and dilated. No signs of inflammation could were normal. While in the clinic the dog had be seen in the gut, peritoneal cavity, or mesena consistently grey, watery, fetid stool. teric lymph nodes. The spleen was symmetrically enlarged to one and one-half times normal size. The duodenum, jejunum and colon *Department of Clinical Studies (Milstein) were biopsied. The retained testicle was reand Department of Pathology (Sanford), Ontario Veterinary College, University of Guelph, Guelph, moved. Normal columnar epithelial cells and goblet Ontario NlG 2W1. Present address of senior author: 1005 Lillooet Road, North Vancouver, cells were seen on impression smears of British Columbia V7J 3H6. jejunum and colon. L27 CAN. VET. JOUR., vol. 18, no. 5, May, 1977
CANADIAN VETERINARY JOURNAL
TABLE I HEMOGRAM OF
Day 1 Day 2
A
DOG WITH INTESTINAL LYMPHANGIECTASIA
Hb PCV Total RBC Total WBC Segmented Band Lymph- Mono- Eosing% % per cu. mm. per cu. mm. neutrophils neutrophils cytes cytes ophils 12.9 34.5 5.6 4830 70 7,000 280 1700 70 14.2 37.8 6.1 3363 57 1500 741 5,700 0
TABLE II BIOCHEMISTRY OF A DOG WITH INTESTINAL
LYMPHANGIECTASIA
Measurement Blood glucose (mg%) SGPT (I.U.) Bilirubin total (mg%) Bilirubin (free) (mg%) Bilirubin (conjugated) (mg%) Cholesterol (mg%) Na+ (mEq/L) K+ (mEq/L) Cl (mEq/L) Ca++ (mg%) BUN (mg%) Total protein (g%) Albumin (g%) a globulin (g%) , globulin (g%) -y globulin (g%)
Value 62 36 0.3 0.1 0.2 106 147.5 5.1 113 8.3 11 7.1 2.7 1.1 1.1 2.2
Histopathological findings in the duodenum and the jejunum were similar, but more pronounced in the jejunum where there was marked dilation of the lymphatic channels of the lamina propria. Villi were short and thickened (stumping atrophy) and the epithelial lining of the villi was intact, but contained numerous goblet cells. Smooth muscle cells of the lamina propria were hypertrophied and there was marked infiltration by lymphocytes and plasma cells (Figure 1). The colon appeared normal histologically. The spleen was markedly congested and lymphoid follicles were atrophied. Testicular hypoplasia and an intratubular seminoma were evident on sections of the retained testicle. A diagnosis of intestinal lymphangiectasia was made on the basis of the histological lesions. The patient developed an intussusception postoperatively and died before surgical correction could be attempted. Autolysis was too far advanced to allow a meaningful post mortem examination. Discussion This case presents certain features common to others reported in the literature, i.e. a protracted course of diarrhea failing to respond to 128
FIGURE 1. Histopathological section of a villus of the jejunum of a dog with lymphangiectasia showing dilated lymphatic channels and mononuclear cell infiltration into the lamina propria. The villus is also short and thick. H&E. X100.
symptomatic treatment, normal pancreatic and liver function tests, normal d-xylose absorption results and histological evidence of dilated intestinal lymphatics (2, 4, 12). It differs from other documented cases in several respects. One major difference is the lack of hypoproteinemia and the accompanying edema and ascites. Hypoproteinemia due to intestinal lymphangiectasia is best confirmed by actual demonstration of excessive protein loss in feces and determination of reduced total body albumin by the use of radio-labelled macromolecules (17). With such techniques it has been
LYMPHANGIECrASIA
found that albumin turnover can increase up to 60% daily from a normal of 5-11% (17), and that hypoproteinemia results from an increase in enteric loss of protein in spite of a marked increase in protein synthesis. It is conceivable that the absence of hypoproteinemia in the case reported was due to a rate of synthesis greater than the rate of loss. Substantiation of this hypothesis was not undertaken. In humans with intestinal lymphangiectasia, a poor correlation between the degree of hypoproteinemia and the severity of the edema suggests that the relationship between diarrhea, hypoproteinemia and edema is not a simple causal one (14). Much evidence is accumulating to show that intestinal lymphangiectasia is only part of a generalized lymphatic abnormality (14). Associated defects documented include hypoplasia of lower extremity lymphatics, obstructed thoracic duct and agenesis of inguinal, pelvic and retroperitoneal nodes. In man, hypoproteinemia and edema are constant and may be the only manifestation of a protein losing enteropathy (17). Gastrointestinal signs, if present, may be of a mild or intermittent nature (14, 17). The severity of the gastrointestinal problems seems to show little relationship to the severity of the edema. Diarrhea seems to be related at least in part to diet (11, 16). The presence of large quantities of fatty acids in the intestinal lumen may act as an irritant. It is difficult, therefore, to predict the degree of hypoproteinemia from a consideration of the gastrointestinal signs alone. Lymphopenia, a prominent feature in man and dogs (2, 4, 12, 17), was also absent in this case. Hypocalcemia is an occasional occurrence in intestinal lymphangiectasia. Serum calcium was in the lower ranges of normal in this case
(8.3 mg%).
The low value of cholesterol recorded (104 mg%) may reflect either loss of chylomicron into the intestinal lumen or inadequate uptake due to impaired lymphatic transport. Total serum globulins and especially gamma globulins usually decrease along with albumin (17). In the present case gamma globulins were actually elevated 2.2 g%. Whereas in humans the average age of onset of symptoms is 11 years with more female cases reported, suggesting a congenital defect, the ages recorded in canine cases range from six months to 14 years (2, 4, 12) with no sex or breed predisposition apparent. Most attempts to link the triad of hypoproteinemia, edema and diarrhea have been based
on the view that the lesion of lymphatic dilation is at fault. Intestinal lymph contains 2040% of the protein concentration of plasma and loss of this fraction could result in significant
hypoproteinemia. Several mechanisms have been proposed to explain the protein loss on the basis of the lymphatic dilation, but the most widely held view is that protein is lost through leakage or rupture of the lacteals into the intestinal lumen (8, 14, 17). Evidence to support this comes from the finding of retrograde flow of contrast material from the intestinal lymphatics into the gut lumen (12); aspiration of chyle from the duodenum and identification of lymphatic fat as opposed to controlled dietary fat (16) and persistence of steatorrhea on low fat diets. The cause of the lymphatic dilation itself remains undetermined in all the canine cases reported. Experimentally, lymphangiectasia and hypoproteinemia have been produced by complete blockage of all mesenteric lymphatics for 12 months, but diarrhea was not produced (3). Regional lymphatic or thoracic duct blockage for as long as six months failed to produce the lesions (1). Intestinal lymphangiectasia is sometimes seen in association with constrictive pericarditis, mesenteric lymphomas, intraperitoneal carcinoma and chronic intraperitoneal inflammation (5). The treatment of intestinal lymphangiectasia, where successful, has been based on relieving the lacteals of their burden and thus reducing the pressure in the lymphatic system. This has been accomplished by feeding low fat diets (11, 16) or using medium chain triglycerides (MCT's) which are absorbed into the portal venous system directly rather than via the lacteals as chylomicrons (7, 9, 10, 16). Feeding of one dog for 36 weeks with a diet containing MCT's failed to relieve hypoproteinemia and ascites (4). It appears that MCT's must be used to the virtual exclusion of long chain fatty acids to be of benefit (6, 9). In our clinic the reversal of hypoproteinemia and edema, in one case, was associated with the use of a commercial "intestinal" diet low in fat.
Summary Intestinal lymphangiectasia is most commonly recognized by signs of edema, ascites, hypoproteinemia and diarrhea. A case is reported where diarrhea was the presenting complaint and irregularities of water distribution and serum protein concentration were not present. 129
CANADLAN VETERINARY JOURNAL
Resume L'oedeme, l'ascite, l'hypoproteinemie et la diarrhee constituent les signes cliniques les plus frequents de la lymphangiectasie intestinale. Les auteurs rapportent un cas de cette condition oiu la diarrhee amena le proprietaire a faire examiner son chien. Cet animal ne presentait cependant pas d'cedeme, d'ascite, ou d'hypoproteinemie.
Acknowledgments
The assistance of Dr. J. H. Reed, Dr. P. W. Pennock and Dr. C. R. Bellenger is gratefully acknowledged.
References 1. BANK, S., G. FISHER, I. N. MARKs and A. 2. 3.
4.
5. 6.
GRALL. The lymphatics of the intestinal mucosa. Am. J. dig. Dis. 12: 619-632. 1967. CAMPBELL, R. S. F., D. BROBST and G. BisGARD. Intestinal lymphangiectasia in a dog. J. Am. vet. med. Ass. 153: 1050-1054. 1968. DANESE, C. A., M. GEORGULAS-PENESIS and A. KARK. Studies of the effects of blockage of intestinal lymphatics. I. Experimental procedure and structural alterations. Am. J. Gastroent. 57: 541-546. 1972. FINCo, D. R., J. R. DUNCAN, W. D. SCHALL, B. E. HOOPER, F. W. CHANDLER and K. A. KEATING. Chronic enteric disease and hypoproteinemia in nine dogs. J. Am. vet. med. Ass. 163: 262-271. 1973. FRANK, B. W. and F. KERN. Intestinal and liver lymph and lymphatics. Gastroent. 55: 408-422. 1968. FRENCH, A. B. Protein-losing gastroenteropathies - Weekly Conference of the Section of Gastroenterorology of the Univ. of Michigan. Am. J. dig. Dis. 16: 661-666. 1971.
7. GREENBERGER, N. J., R. D. RUPPERT and M. TZAGOURNIS. Use of medium chain triglycerides in malabsorption. Ann. intern. Med. 66: 727-734. 1967. 8. HILL, F. W. G., D. E. KIDDER and J. FREw. A xylose absorption test for the dog. Vet. Rec. 87: 250-255. 1970. 9. HOLT, P. R. Medium chain triglycerides: Their absorption, metabolism and clinical applications. In Progress in Gastroenterology. G. B. S. Glass, Editor. pp. 227-298. New York: Grune and Stratton. 1968. 10. HOLT, P. R. Dietary treatment of protein loss in intestinal lymphangiectasia. Pediat. 34: 629-635. 1964. 11. JEFFRIES, G. H., A. CHAPMAN and M. SLEISINGER. Low fat diet in intestinal lymphangiectasia. New Engl. J. Med. 270: 761-766. 1964. 12. MATTHEEUWS, A., A. DERICK, H. THOONEN and J. VAN DER STOCK. Intestinal lymphangiectasia in a dog. J. small Anim. Prac. 15: 757-761. 1974. 13. MISTILIS, S. P., A. P. SKYNING and D. D. STEPHEN. Intestinal lymphangiectasia. Mechanism of enteric loss of plasma-protein and fat. Lancet 1: 77-79. 1965. 14. POMERANTZ, M. and T. A. WALDMANN. Systemic lymphatic abnormalities associated with gastrointestinal protein loss secondary to intestinal lymphangiectasia. Gastroent. 45: 703-711. 1963. 15. STOELING, G. B. A., P. J. J. VAN MUNSTER and J. P. SLOOFF. Chylous effusions into the intestine in a patient with protein losing gastorenteropathy. Pediat. 31: 1011-1018. 1963. 16. VESCiA, F. G. and J. H. DAVIS. Comments. Treatment of Intestinal lymphangiectasia. Gastroent. 48: 287. 1965. 17. WALDMANN, T. A. Protein losing enteropathy. Gastroent. 50: 422-433. 1966.
130
CANADIAN VETERINARY JOURNAL
TABLE I HEMOGRAM OF
Day 1 Day 2
A
DOG WITH INTESTINAL LYMPHANGIECTASIA
Hb PCV Total RBC Total WBC Segmented Band Lymph- Mono- Eosing% % per cu. mm. per cu. mm. neutrophils neutrophils cytes cytes ophils 12.9 34.5 5.6 4830 70 7,000 280 1700 70 14.2 37.8 6.1 3363 57 1500 741 5,700 0
TABLE II BIOCHEMISTRY OF A DOG WITH INTESTINAL
LYMPHANGIECTASIA
Measurement Blood glucose (mg%) SGPT (I.U.) Bilirubin total (mg%) Bilirubin (free) (mg%) Bilirubin (conjugated) (mg%) Cholesterol (mg%) Na+ (mEq/L) K+ (mEq/L) Cl (mEq/L) Ca++ (mg%) BUN (mg%) Total protein (g%) Albumin (g%) a globulin (g%) , globulin (g%) -y globulin (g%)
Value 62 36 0.3 0.1 0.2 106 147.5 5.1 113 8.3 11 7.1 2.7 1.1 1.1 2.2
Histopathological findings in the duodenum and the jejunum were similar, but more pronounced in the jejunum where there was marked dilation of the lymphatic channels of the lamina propria. Villi were short and thickened (stumping atrophy) and the epithelial lining of the villi was intact, but contained numerous goblet cells. Smooth muscle cells of the lamina propria were hypertrophied and there was marked infiltration by lymphocytes and plasma cells (Figure 1). The colon appeared normal histologically. The spleen was markedly congested and lymphoid follicles were atrophied. Testicular hypoplasia and an intratubular seminoma were evident on sections of the retained testicle. A diagnosis of intestinal lymphangiectasia was made on the basis of the histological lesions. The patient developed an intussusception postoperatively and died before surgical correction could be attempted. Autolysis was too far advanced to allow a meaningful post mortem examination. Discussion This case presents certain features common to others reported in the literature, i.e. a protracted course of diarrhea failing to respond to 128
FIGURE 1. Histopathological section of a villus of the jejunum of a dog with lymphangiectasia showing dilated lymphatic channels and mononuclear cell infiltration into the lamina propria. The villus is also short and thick. H&E. X100.
symptomatic treatment, normal pancreatic and liver function tests, normal d-xylose absorption results and histological evidence of dilated intestinal lymphatics (2, 4, 12). It differs from other documented cases in several respects. One major difference is the lack of hypoproteinemia and the accompanying edema and ascites. Hypoproteinemia due to intestinal lymphangiectasia is best confirmed by actual demonstration of excessive protein loss in feces and determination of reduced total body albumin by the use of radio-labelled macromolecules (17). With such techniques it has been
LYMPHANGIECrASIA
found that albumin turnover can increase up to 60% daily from a normal of 5-11% (17), and that hypoproteinemia results from an increase in enteric loss of protein in spite of a marked increase in protein synthesis. It is conceivable that the absence of hypoproteinemia in the case reported was due to a rate of synthesis greater than the rate of loss. Substantiation of this hypothesis was not undertaken. In humans with intestinal lymphangiectasia, a poor correlation between the degree of hypoproteinemia and the severity of the edema suggests that the relationship between diarrhea, hypoproteinemia and edema is not a simple causal one (14). Much evidence is accumulating to show that intestinal lymphangiectasia is only part of a generalized lymphatic abnormality (14). Associated defects documented include hypoplasia of lower extremity lymphatics, obstructed thoracic duct and agenesis of inguinal, pelvic and retroperitoneal nodes. In man, hypoproteinemia and edema are constant and may be the only manifestation of a protein losing enteropathy (17). Gastrointestinal signs, if present, may be of a mild or intermittent nature (14, 17). The severity of the gastrointestinal problems seems to show little relationship to the severity of the edema. Diarrhea seems to be related at least in part to diet (11, 16). The presence of large quantities of fatty acids in the intestinal lumen may act as an irritant. It is difficult, therefore, to predict the degree of hypoproteinemia from a consideration of the gastrointestinal signs alone. Lymphopenia, a prominent feature in man and dogs (2, 4, 12, 17), was also absent in this case. Hypocalcemia is an occasional occurrence in intestinal lymphangiectasia. Serum calcium was in the lower ranges of normal in this case
(8.3 mg%).
The low value of cholesterol recorded (104 mg%) may reflect either loss of chylomicron into the intestinal lumen or inadequate uptake due to impaired lymphatic transport. Total serum globulins and especially gamma globulins usually decrease along with albumin (17). In the present case gamma globulins were actually elevated 2.2 g%. Whereas in humans the average age of onset of symptoms is 11 years with more female cases reported, suggesting a congenital defect, the ages recorded in canine cases range from six months to 14 years (2, 4, 12) with no sex or breed predisposition apparent. Most attempts to link the triad of hypoproteinemia, edema and diarrhea have been based
on the view that the lesion of lymphatic dilation is at fault. Intestinal lymph contains 2040% of the protein concentration of plasma and loss of this fraction could result in significant
hypoproteinemia. Several mechanisms have been proposed to explain the protein loss on the basis of the lymphatic dilation, but the most widely held view is that protein is lost through leakage or rupture of the lacteals into the intestinal lumen (8, 14, 17). Evidence to support this comes from the finding of retrograde flow of contrast material from the intestinal lymphatics into the gut lumen (12); aspiration of chyle from the duodenum and identification of lymphatic fat as opposed to controlled dietary fat (16) and persistence of steatorrhea on low fat diets. The cause of the lymphatic dilation itself remains undetermined in all the canine cases reported. Experimentally, lymphangiectasia and hypoproteinemia have been produced by complete blockage of all mesenteric lymphatics for 12 months, but diarrhea was not produced (3). Regional lymphatic or thoracic duct blockage for as long as six months failed to produce the lesions (1). Intestinal lymphangiectasia is sometimes seen in association with constrictive pericarditis, mesenteric lymphomas, intraperitoneal carcinoma and chronic intraperitoneal inflammation (5). The treatment of intestinal lymphangiectasia, where successful, has been based on relieving the lacteals of their burden and thus reducing the pressure in the lymphatic system. This has been accomplished by feeding low fat diets (11, 16) or using medium chain triglycerides (MCT's) which are absorbed into the portal venous system directly rather than via the lacteals as chylomicrons (7, 9, 10, 16). Feeding of one dog for 36 weeks with a diet containing MCT's failed to relieve hypoproteinemia and ascites (4). It appears that MCT's must be used to the virtual exclusion of long chain fatty acids to be of benefit (6, 9). In our clinic the reversal of hypoproteinemia and edema, in one case, was associated with the use of a commercial "intestinal" diet low in fat.
Summary Intestinal lymphangiectasia is most commonly recognized by signs of edema, ascites, hypoproteinemia and diarrhea. A case is reported where diarrhea was the presenting complaint and irregularities of water distribution and serum protein concentration were not present. 129
CANADLAN VETERINARY JOURNAL
Resume L'oedeme, l'ascite, l'hypoproteinemie et la diarrhee constituent les signes cliniques les plus frequents de la lymphangiectasie intestinale. Les auteurs rapportent un cas de cette condition oiu la diarrhee amena le proprietaire a faire examiner son chien. Cet animal ne presentait cependant pas d'cedeme, d'ascite, ou d'hypoproteinemie.
Acknowledgments
The assistance of Dr. J. H. Reed, Dr. P. W. Pennock and Dr. C. R. Bellenger is gratefully acknowledged.
References 1. BANK, S., G. FISHER, I. N. MARKs and A. 2. 3.
4.
5. 6.
GRALL. The lymphatics of the intestinal mucosa. Am. J. dig. Dis. 12: 619-632. 1967. CAMPBELL, R. S. F., D. BROBST and G. BisGARD. Intestinal lymphangiectasia in a dog. J. Am. vet. med. Ass. 153: 1050-1054. 1968. DANESE, C. A., M. GEORGULAS-PENESIS and A. KARK. Studies of the effects of blockage of intestinal lymphatics. I. Experimental procedure and structural alterations. Am. J. Gastroent. 57: 541-546. 1972. FINCo, D. R., J. R. DUNCAN, W. D. SCHALL, B. E. HOOPER, F. W. CHANDLER and K. A. KEATING. Chronic enteric disease and hypoproteinemia in nine dogs. J. Am. vet. med. Ass. 163: 262-271. 1973. FRANK, B. W. and F. KERN. Intestinal and liver lymph and lymphatics. Gastroent. 55: 408-422. 1968. FRENCH, A. B. Protein-losing gastroenteropathies - Weekly Conference of the Section of Gastroenterorology of the Univ. of Michigan. Am. J. dig. Dis. 16: 661-666. 1971.
7. GREENBERGER, N. J., R. D. RUPPERT and M. TZAGOURNIS. Use of medium chain triglycerides in malabsorption. Ann. intern. Med. 66: 727-734. 1967. 8. HILL, F. W. G., D. E. KIDDER and J. FREw. A xylose absorption test for the dog. Vet. Rec. 87: 250-255. 1970. 9. HOLT, P. R. Medium chain triglycerides: Their absorption, metabolism and clinical applications. In Progress in Gastroenterology. G. B. S. Glass, Editor. pp. 227-298. New York: Grune and Stratton. 1968. 10. HOLT, P. R. Dietary treatment of protein loss in intestinal lymphangiectasia. Pediat. 34: 629-635. 1964. 11. JEFFRIES, G. H., A. CHAPMAN and M. SLEISINGER. Low fat diet in intestinal lymphangiectasia. New Engl. J. Med. 270: 761-766. 1964. 12. MATTHEEUWS, A., A. DERICK, H. THOONEN and J. VAN DER STOCK. Intestinal lymphangiectasia in a dog. J. small Anim. Prac. 15: 757-761. 1974. 13. MISTILIS, S. P., A. P. SKYNING and D. D. STEPHEN. Intestinal lymphangiectasia. Mechanism of enteric loss of plasma-protein and fat. Lancet 1: 77-79. 1965. 14. POMERANTZ, M. and T. A. WALDMANN. Systemic lymphatic abnormalities associated with gastrointestinal protein loss secondary to intestinal lymphangiectasia. Gastroent. 45: 703-711. 1963. 15. STOELING, G. B. A., P. J. J. VAN MUNSTER and J. P. SLOOFF. Chylous effusions into the intestine in a patient with protein losing gastorenteropathy. Pediat. 31: 1011-1018. 1963. 16. VESCiA, F. G. and J. H. DAVIS. Comments. Treatment of Intestinal lymphangiectasia. Gastroent. 48: 287. 1965. 17. WALDMANN, T. A. Protein losing enteropathy. Gastroent. 50: 422-433. 1966.
130
