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Giardiasis
Vol. 52, No.2, Part 1 Printed in U.S .A.
GASTROENTEROLOGY
Copyright © 1967 by The Williams & Wilkins Co.
COMMENTS Readers are invited to contribute Comments. If found suitable, they will be published promptly, subject to the usual editing. They should be typewritten double spaced and sent to the Editor.
GIARDIASIS A number of investigations have indicated that Giardia lamblia may cause diarrheal disease in man, sometimes with associated malabsorption. Therapy of the giardiasis often leads to a cure. But not all observers have agreed with these findings. The apparent failure of G. lamblia to invade host tissues has been cited as major evidence that this host-parasite relationship is solely commensal. Demonstration of tissue invasion by Brandborg et al. l and Morecki and Parker 2 will not only help greatly to improve our understanding of the pathogenesis of this parasite, but will also help put to rest controversy regarding potential pathogenicity of G. lamblia for man. The response of individuals to exposure to Giardia lamblia is quite variable. This may be based either upon a variation in the parasite itself or upon differences in patient susceptibility. Diversified virulence of G. lamblia remains only a theoretical consideration. Patient variability was well shown in Rendtorff's experimental study.3 Forty men were fed a single strain of the organism at different dose levels and only 21 became infected. Most were asymtomatic but 9 noted a change in stool pattern. One variable was the infecting dose. Although ingestion of as few as 10 cysts led to infection in some individuals, ingestion of 100 or more Giardia cysts was required to guarantee infection. The infestation cleared spontaneously in most of the men after a brief period, but in 2 men stools Address requests for reprints to : Dr. Theodore M. Bayless, Johns Hopkins Hospital, Baltimore, Maryland 21205. 301
were positive for G. lamblia for more than 3 months. Host-related factors also contribute to variable human susceptibility to giardiasis. Childhood is probably one such factor. Children harbor Giardia more frequently than adults and are perhaps more vulnerable to its effects.4. 5 Gastrectomy in adults may enhance their susceptibility.6.7 More cases must be studied to establish this fact firmly, but there is already evidence that gastric surgery predisposes to other forms of bowel infection. 8 • 9 y-Globulin abnormalities associated with giardiasis have been reported.lO. 11 H ermans et al.l 2 have recently described 7 patients demonstrating nodular lymphoid hyperplasia in the jejunum and hypogammaglobulinemia. There was marked lowering of the IgA and IgM globulins. Six of the 7 patients also had giardiasis. Those individuals continued to show their dysgammaglobulinemia after treatment of the giardiasis, unlike some patients. with giardiasis and malabsorption who may have a secondary hypoglobulinemia that disappears after treatment. The relationship between jejunal lymphoid hyperplasia, dysgammaglobulinemia, and giardiasis is not clear. Hermans e t al.l 2 felt that G. lamblia might be playing strictly an opportunistic role in their patients, but this must be a tentative conclusion. Thus the possibility is good that altered immune mechanisms may be a significant factor in susceptibility to giardiasis. Enteric bacterial infection and malnutrition are two conditions that may be highly relevant to susceptibility to giardiasis. This is borne out in a recent study of children
302
COMMENTS
with diarrhea in West Pakistan.13 A group of children with diarrheal illness was investigated for the presence of enteropathogenic bacteria and parasites, and compared with similar but nondiarrheal controls. Malnutrition was common in both groups. Giardiasis was found in 32% of the diarrheal patients versus only 19% of the controls. Heavy bacterial overgrowth in the small bowel in conjunction with giardiasis has also been described in adults. 7,14 In a recent study from Cali, Colombiap treatment of malnutrition alone corrected malabsorption in a patient with giardiasis. It is likely that bacteria, malnutrition, and G. lamblia operate synergistically to give enhanced pathogenicity, but the mechanism of this association appears to be complex and is certainly poorly understood. A broad spectrum of clinical manifestations is found in giardiasis. 16 Some subjects show no symptoms while others may have severe diarrhea. The disease may be brief and self-limited, or there may be a long history of mild, intermittent diarrhea and abdominal bloating that responds to therapy for giardiasis. An altered gastrointestinal pattern by X-ray may also be evident.n A chronic malabsorption syndrome occurs in some patients infested with Giardia.2, 4-7, 14, 17-20 While the occurrence of malabsorption due to giardiasis now seems hardly debatable, the pathogenesis of malabsorption in this disease has not been fully established. Factors that have been suggested include: injury to the intestinal mucosa,7, 21 creation of a mechanical barrier to absorption by the massive numbers. of parasites on the mucosal surface,2, 18 irritation of the mucosa with an outpouring of mucus and fluid, altered motility,17 competition between organisms and the host for nutrients,2° and a possible anti folate effect that simulates folic acid or vitamin B12 deficiency.1 Malnutrition 15 , 20 and effects of bacteria associated with giardiasis 7 have also been suggested as possible factors in the pathogenesis of malabsorption with giardiasis. Several auth ors 6, 7, 20, 22 have shown that significant jejunal mucosal alterations do occur in some patients with giardiasis.
Vol. 52, No.2, Part 1
These are generally less severe than those found in celiac disease. Lesions noted have included abnormal configuration of the villi, acute and chronic inflammation, increased epithelial mitotic figures, and epithelial cell damage. Further evidence of mucosal derangement has been supplied by electron microscopy21 and demonstration of lactose intolerance. 23 While there may be some correlation between severity of mucosal injury and occurrence of malabsorption,7 the correlation is by no means perfect. It is possible that only patients with severe chronic malabsorption, such as some of those described by Yardley et aU and Zamcheck et al.,20 will have marked alterations by light microscopy. The case described by Morecki and Parker 2 would conform with this correlation since their patient had mild asymtomatic malabsorption and the intestinal biopsy was normal by light microscopy. Their patient did have jejunal epithelial changes, however, by electron microscopy. It is still difficult to interpret fully the significance of jejunal invasion by giardia parasites as described by Brandborg et al. 1 Their observation that organisms could be demonstrated in the jejunal tissue only in symptomatic patients strongly suggests that tissue invasiveness could be a factor in pathogenicity. Invasiveness could also be a principal cause of mucosal injury. But this is not yet clear because of the small number of invading organisms found, and it may still be that the many organisms remaining within the lumen are largely responsible for the pathogenic effects. Brandborg et aU have suggested a possible anti folate effect on the intestinal mucosa on the basis of increased nuclear size in the crypts of Lieberklihn. Since immature nuclei are typically of larger size, however, these changes may simply reflect a greater epithelial cell turnover. In addition, folic acid would be expected to cause symptomatic improvement, as in tropical sprue and, to our knowledge, this has not been demonstrated. Careful stool examination is the key to diagnosis of giardiasis in most patients. A single search for stool parasites, however,
F ebl'uary 1967
303
COMMENTS
may not be sufficient. Duodenal aspiration24 is essential for detection of giardiasis in those rare patients whose stools for G. lamblia are repeatedly negative. Stained smears of mucus obtained from a biopsy instrument serve admirably for this purpose. In some instances the biopsy itself leads to a diagnosis of giardiasis. The organisms are usually easily detected in the specimens. Nonspecific histological clues ' that may be noted first are: acute and chronic inflammation, significant nodular hyperplasia of lymphoid tissue, or increased epithelial mitoses. All jejunal biopsies should be scanned for the presence of Giardia organisms, but this should be done with special care when the patient has unexplained diarrhea or malabsorption. Another helpful diagnostic clue can be a history of travel, particularly to tropical or developing regions of the world. A recent outbreak of giardiasis, usually with acute diarrhea and affecting 25 persons, was traced to the ski resort, Aspen, Colorado.25 The best initial step in the management of symptomatic giardiasis is usually therapy with quinacrine (Atabrine). A single course of quinacrine at the standard level may be ineffective, however, especially in very chronic cases of giardiasis. Hence, failure to respond symptomatically to one or more courses of quinacrine is insufficient evidence that G. lamblia was not the original cause of the patient's symptoms. We have seen patients who remained symptomatic after quinacrine despite absence of stool parasites, but they had organisms still present in duodenal aspirates. P atients who initially become asymptomatic after quinacrine may also have later recurrences. One should also consider the possibility of using drugs other than quinacrine, such as diiodohydroxyquin, in resist ant cases. 26 It is clear that Giardia Lamblia can be pathogenic in man. It is equally clear from the foregoing that there is still much to be learned about susceptibility to infestation and the mechanisms by which G. lamblia leads to disease. Our information about t hi s organism in areas of the world where the chronic infestation rate is high is es-
pecially limited. Infected residents of those areas, which are frequently tropical and poorly developed, are said usually to suffer little or no deleterious effects. There have been, however, few detailed clinical studies of these patients in regard to either Giardia or other parasites. Furthermore, such investigations are inherently difficult to assess because of the common occurrence of malnutrition, multiple types of parasites, and perhaps other poorly understood superimposed factors. Thus the possibility remains that significant clinical consequences of giardiasis may be widespread in areas of high infestation. John H. Yardley, M.D. Th eodore M. Bayless, M .D. Departments of Pathology and Medicine Johns Hopkins Hospital Baltimore, Mm'yland 21205 REFERENCES 1. Brandborg, L. L., C. B. Tankersley, S. Gottlieb, M . Barancik, and V. E. Sartor. 1967.
2.
3.
4. 5.
Histological demonstration of mucosal invasion by Giardia lamblia in man. Gastroenterology 52: 143-150. Morecki, R., and J. G. Parker. 1967. Ultrastructural studies of the human Giardia lamb lia and subjacent jejunal mucosa in a subject with steatorrhea. Gastroenterology 52: 151-164. Rendtorff, R. C. 1954. The experimental transmission of human intestinal protozoan parasites. II. Giardia lamblia cysts given in capsules. Amer. J. Hyg. 59: 209-220. Veghelyi, P. V. 1938. Giardiasis in children. Amer. J. Dis. Child. 56: 1231-1241. Cortner, J . A. 1959. Giardiasis, a cause of celiac syndrome. Amer. J. Dis. Child. 98: 311-316.
6. Vachon, A., P . Paliard, B. Mouliner, M. Rochet, and M. Abry. 1963. Diagnostic par biopsie jejunale d'une diarrhee chronique a lamblia avec syndrome de denutrition (2 observations). Arch. Mal. Appar. Dig. 52: 355-359. 7. Yardley, J . H., J . Takano, and T. R. H endrix. 1964. Epithelial and other mucosal lesions of the jejunum in giardiasis. Jejunal biopsy studies. Bull. Hopkins Hosp. 115: 389-406. 8. Waddell, W. R., and L. J. Kunz. 1956. Asso-
ciation of salmonella enteritis with opera-
COMMENTS
304
Vol. 52, No.2, Part 1
tions on the stomach. New Eng. J. Med.
17. Peterson, G. M. 1957. Intestinal changes in
255: 555-559.
Giardia lamblia infestation. Amer. J. Roentgen. 77: 670-677. 18. Veghelyi, P. V. 1939. Celiac disease initiated by giardiasis. Amer. J. Dis. Child. 57: 894-
9. Mortimer, D. C., P. I. Reed, M. Vidinili, and J. M. Finlay. 1964. The role of the upper gastrointestinal flora in the malabsorption syndrome. Canad. Med. Assn. J. 90: 559-564. 10. Uszynski, M. 1962. A case of hypogammaglobulinemia and secondary infantilism in a patient with chronic infection with lamblia intestinalis. Wiad. Parazyt. 8: 469-473. 11. Palumbo, P. J., H. H. Scudamore, and J. H. Thompson, Jr. 1962. Relationship of infestation with Giardia Lamblia to intestinalmalabsorption syndromes. Proc. Mayo Clin. 37: 589-598. 12. Hermans, P. E., K. A. Huizenga, H. N. Hoffman, A. L. Brown, Jr., and H. Markowitz. 1966. Dysgammaglobulinemia associated with nodular lymphoid hyperplasia of the small intestine. Amer. J. Med. 40: 78--89. 13. Ingram, V. 0., F. L. Rights, H. A. Khan, K. Hashimi, and K. Ansani. 1966. Diarrhea In children of West Pakistan : occurrence of bacterial and parasitic agents. Amer. J. Trop. Med. Hyg. 15: 743-750. 14. Ligny, G. 1961. Jejuno-ileites mixtes a lamblias staphylocoques. Arch. Mal. Appar. Dig. 50: 1162-2. 15. Mayoral, L. G., K. Tripathy, F. T. Garcia, and J. Ghitis. 1966. Intestinal malabsorption and parasitic disease: the role of protein malnutrition. Gastroenterology 50: 856--857. 16. Hartman, H. R., and F. A. Kyser. 1941.
Giardiasis and its treatment. J. A. M. A. 116: 2835-2839.
899. 19. Amini, F. 1963. Giardiasis and steatorrhoea. J. Trop. Med. Hyg. 66: 190-192. 20. Zamcheck, N., L. C. Hoskins, S. J. Winawer,
2!.
22.
23.
24.
25. 26.
S. A. Broitman, and L. S. Gottlieb. 1963. Histology and ultrastructure of the parasite and the intestinal mucosa in human giardiasis: effects of Antabrine therapy. Gastroenterology 44: 860. Takano, J ., and J. H. Yardley. 1965. Jejunal lesions in patients with giardiasis and malabsorption. An electron microscopic study. Bull. Hopkins Hosp. 116: 413-429. Cameron, A. H., R. Astley, M. Hallowell, A. B. Rawson, C. G. Miller, J . M. French, and D. V. Hubble. 1962. Duodenal-jejunal biopsy in the investigation of children with coeliac disease. Quart. J. Med. 31: 125-140. Durand, P . 1964. Lactose intolerance, p. 131132. In P. Durand [ed.], Disorders due to intestinal d efective carbohydrate di gestion and absorption. Pensiero Scientifico, Rome. Paulson, M., and J. Andrews. 1930. The incidence of human intestinal protozoa in duodenal aspirates. J. A. M. A. 94: 2063-2065. Anonymous. 1966. Giardiasis outbreak hits Aspen skiers. Mod. Med. 34 (No. 11): 32. Goodman, L. S., and A.Gilman. 1965. The pharmacological basis of therapeutics, Ed. 3, p. 1131. The MacMillan Company, New York.
MAXIMAL ACID SECRETION IN MAN In commenting on the paper of Makhlouf et al} Dr. Grossman 2 has again focused our attention on an important facet of gastric physiology-the assessment of the greatest output of hydrogen ions which the stomach of an individual can produce. Since Makhlouf suggests that "maximal secretory capacity" can be deduced mathematically, may I put in a word for an empirical approach to this index of gastric function? The synthesis of gastrin and polypeptide derivatives has made available new, powerful, gastric secretory stimulants which can be applied to the more rigorous evaluation
of gastric acid production in man. Using these hormones, it is possible in most individuals to define a level of gastric acid output which cannot be increased by increasing the dose of secretory stimulant. It is therefore possible to demonstrate, routinely, the greatest output of acid of which any stomach is capable, at least in response to these stimulants. It is at present a matter of conjecture whether a greater response might result from other gastric stimulants or combinations of stimulants. The ability of histamine or betazole to elicit maximal gastric secretion in human subjects is difficult to assess,
GASTROENTEROLOGY
Copyright © 1967 by The Williams & Wilkins Co.
COMMENTS Readers are invited to contribute Comments. If found suitable, they will be published promptly, subject to the usual editing. They should be typewritten double spaced and sent to the Editor.
GIARDIASIS A number of investigations have indicated that Giardia lamblia may cause diarrheal disease in man, sometimes with associated malabsorption. Therapy of the giardiasis often leads to a cure. But not all observers have agreed with these findings. The apparent failure of G. lamblia to invade host tissues has been cited as major evidence that this host-parasite relationship is solely commensal. Demonstration of tissue invasion by Brandborg et al. l and Morecki and Parker 2 will not only help greatly to improve our understanding of the pathogenesis of this parasite, but will also help put to rest controversy regarding potential pathogenicity of G. lamblia for man. The response of individuals to exposure to Giardia lamblia is quite variable. This may be based either upon a variation in the parasite itself or upon differences in patient susceptibility. Diversified virulence of G. lamblia remains only a theoretical consideration. Patient variability was well shown in Rendtorff's experimental study.3 Forty men were fed a single strain of the organism at different dose levels and only 21 became infected. Most were asymtomatic but 9 noted a change in stool pattern. One variable was the infecting dose. Although ingestion of as few as 10 cysts led to infection in some individuals, ingestion of 100 or more Giardia cysts was required to guarantee infection. The infestation cleared spontaneously in most of the men after a brief period, but in 2 men stools Address requests for reprints to : Dr. Theodore M. Bayless, Johns Hopkins Hospital, Baltimore, Maryland 21205. 301
were positive for G. lamblia for more than 3 months. Host-related factors also contribute to variable human susceptibility to giardiasis. Childhood is probably one such factor. Children harbor Giardia more frequently than adults and are perhaps more vulnerable to its effects.4. 5 Gastrectomy in adults may enhance their susceptibility.6.7 More cases must be studied to establish this fact firmly, but there is already evidence that gastric surgery predisposes to other forms of bowel infection. 8 • 9 y-Globulin abnormalities associated with giardiasis have been reported.lO. 11 H ermans et al.l 2 have recently described 7 patients demonstrating nodular lymphoid hyperplasia in the jejunum and hypogammaglobulinemia. There was marked lowering of the IgA and IgM globulins. Six of the 7 patients also had giardiasis. Those individuals continued to show their dysgammaglobulinemia after treatment of the giardiasis, unlike some patients. with giardiasis and malabsorption who may have a secondary hypoglobulinemia that disappears after treatment. The relationship between jejunal lymphoid hyperplasia, dysgammaglobulinemia, and giardiasis is not clear. Hermans e t al.l 2 felt that G. lamblia might be playing strictly an opportunistic role in their patients, but this must be a tentative conclusion. Thus the possibility is good that altered immune mechanisms may be a significant factor in susceptibility to giardiasis. Enteric bacterial infection and malnutrition are two conditions that may be highly relevant to susceptibility to giardiasis. This is borne out in a recent study of children
302
COMMENTS
with diarrhea in West Pakistan.13 A group of children with diarrheal illness was investigated for the presence of enteropathogenic bacteria and parasites, and compared with similar but nondiarrheal controls. Malnutrition was common in both groups. Giardiasis was found in 32% of the diarrheal patients versus only 19% of the controls. Heavy bacterial overgrowth in the small bowel in conjunction with giardiasis has also been described in adults. 7,14 In a recent study from Cali, Colombiap treatment of malnutrition alone corrected malabsorption in a patient with giardiasis. It is likely that bacteria, malnutrition, and G. lamblia operate synergistically to give enhanced pathogenicity, but the mechanism of this association appears to be complex and is certainly poorly understood. A broad spectrum of clinical manifestations is found in giardiasis. 16 Some subjects show no symptoms while others may have severe diarrhea. The disease may be brief and self-limited, or there may be a long history of mild, intermittent diarrhea and abdominal bloating that responds to therapy for giardiasis. An altered gastrointestinal pattern by X-ray may also be evident.n A chronic malabsorption syndrome occurs in some patients infested with Giardia.2, 4-7, 14, 17-20 While the occurrence of malabsorption due to giardiasis now seems hardly debatable, the pathogenesis of malabsorption in this disease has not been fully established. Factors that have been suggested include: injury to the intestinal mucosa,7, 21 creation of a mechanical barrier to absorption by the massive numbers. of parasites on the mucosal surface,2, 18 irritation of the mucosa with an outpouring of mucus and fluid, altered motility,17 competition between organisms and the host for nutrients,2° and a possible anti folate effect that simulates folic acid or vitamin B12 deficiency.1 Malnutrition 15 , 20 and effects of bacteria associated with giardiasis 7 have also been suggested as possible factors in the pathogenesis of malabsorption with giardiasis. Several auth ors 6, 7, 20, 22 have shown that significant jejunal mucosal alterations do occur in some patients with giardiasis.
Vol. 52, No.2, Part 1
These are generally less severe than those found in celiac disease. Lesions noted have included abnormal configuration of the villi, acute and chronic inflammation, increased epithelial mitotic figures, and epithelial cell damage. Further evidence of mucosal derangement has been supplied by electron microscopy21 and demonstration of lactose intolerance. 23 While there may be some correlation between severity of mucosal injury and occurrence of malabsorption,7 the correlation is by no means perfect. It is possible that only patients with severe chronic malabsorption, such as some of those described by Yardley et aU and Zamcheck et al.,20 will have marked alterations by light microscopy. The case described by Morecki and Parker 2 would conform with this correlation since their patient had mild asymtomatic malabsorption and the intestinal biopsy was normal by light microscopy. Their patient did have jejunal epithelial changes, however, by electron microscopy. It is still difficult to interpret fully the significance of jejunal invasion by giardia parasites as described by Brandborg et al. 1 Their observation that organisms could be demonstrated in the jejunal tissue only in symptomatic patients strongly suggests that tissue invasiveness could be a factor in pathogenicity. Invasiveness could also be a principal cause of mucosal injury. But this is not yet clear because of the small number of invading organisms found, and it may still be that the many organisms remaining within the lumen are largely responsible for the pathogenic effects. Brandborg et aU have suggested a possible anti folate effect on the intestinal mucosa on the basis of increased nuclear size in the crypts of Lieberklihn. Since immature nuclei are typically of larger size, however, these changes may simply reflect a greater epithelial cell turnover. In addition, folic acid would be expected to cause symptomatic improvement, as in tropical sprue and, to our knowledge, this has not been demonstrated. Careful stool examination is the key to diagnosis of giardiasis in most patients. A single search for stool parasites, however,
F ebl'uary 1967
303
COMMENTS
may not be sufficient. Duodenal aspiration24 is essential for detection of giardiasis in those rare patients whose stools for G. lamblia are repeatedly negative. Stained smears of mucus obtained from a biopsy instrument serve admirably for this purpose. In some instances the biopsy itself leads to a diagnosis of giardiasis. The organisms are usually easily detected in the specimens. Nonspecific histological clues ' that may be noted first are: acute and chronic inflammation, significant nodular hyperplasia of lymphoid tissue, or increased epithelial mitoses. All jejunal biopsies should be scanned for the presence of Giardia organisms, but this should be done with special care when the patient has unexplained diarrhea or malabsorption. Another helpful diagnostic clue can be a history of travel, particularly to tropical or developing regions of the world. A recent outbreak of giardiasis, usually with acute diarrhea and affecting 25 persons, was traced to the ski resort, Aspen, Colorado.25 The best initial step in the management of symptomatic giardiasis is usually therapy with quinacrine (Atabrine). A single course of quinacrine at the standard level may be ineffective, however, especially in very chronic cases of giardiasis. Hence, failure to respond symptomatically to one or more courses of quinacrine is insufficient evidence that G. lamblia was not the original cause of the patient's symptoms. We have seen patients who remained symptomatic after quinacrine despite absence of stool parasites, but they had organisms still present in duodenal aspirates. P atients who initially become asymptomatic after quinacrine may also have later recurrences. One should also consider the possibility of using drugs other than quinacrine, such as diiodohydroxyquin, in resist ant cases. 26 It is clear that Giardia Lamblia can be pathogenic in man. It is equally clear from the foregoing that there is still much to be learned about susceptibility to infestation and the mechanisms by which G. lamblia leads to disease. Our information about t hi s organism in areas of the world where the chronic infestation rate is high is es-
pecially limited. Infected residents of those areas, which are frequently tropical and poorly developed, are said usually to suffer little or no deleterious effects. There have been, however, few detailed clinical studies of these patients in regard to either Giardia or other parasites. Furthermore, such investigations are inherently difficult to assess because of the common occurrence of malnutrition, multiple types of parasites, and perhaps other poorly understood superimposed factors. Thus the possibility remains that significant clinical consequences of giardiasis may be widespread in areas of high infestation. John H. Yardley, M.D. Th eodore M. Bayless, M .D. Departments of Pathology and Medicine Johns Hopkins Hospital Baltimore, Mm'yland 21205 REFERENCES 1. Brandborg, L. L., C. B. Tankersley, S. Gottlieb, M . Barancik, and V. E. Sartor. 1967.
2.
3.
4. 5.
Histological demonstration of mucosal invasion by Giardia lamblia in man. Gastroenterology 52: 143-150. Morecki, R., and J. G. Parker. 1967. Ultrastructural studies of the human Giardia lamb lia and subjacent jejunal mucosa in a subject with steatorrhea. Gastroenterology 52: 151-164. Rendtorff, R. C. 1954. The experimental transmission of human intestinal protozoan parasites. II. Giardia lamblia cysts given in capsules. Amer. J. Hyg. 59: 209-220. Veghelyi, P. V. 1938. Giardiasis in children. Amer. J. Dis. Child. 56: 1231-1241. Cortner, J . A. 1959. Giardiasis, a cause of celiac syndrome. Amer. J. Dis. Child. 98: 311-316.
6. Vachon, A., P . Paliard, B. Mouliner, M. Rochet, and M. Abry. 1963. Diagnostic par biopsie jejunale d'une diarrhee chronique a lamblia avec syndrome de denutrition (2 observations). Arch. Mal. Appar. Dig. 52: 355-359. 7. Yardley, J . H., J . Takano, and T. R. H endrix. 1964. Epithelial and other mucosal lesions of the jejunum in giardiasis. Jejunal biopsy studies. Bull. Hopkins Hosp. 115: 389-406. 8. Waddell, W. R., and L. J. Kunz. 1956. Asso-
ciation of salmonella enteritis with opera-
COMMENTS
304
Vol. 52, No.2, Part 1
tions on the stomach. New Eng. J. Med.
17. Peterson, G. M. 1957. Intestinal changes in
255: 555-559.
Giardia lamblia infestation. Amer. J. Roentgen. 77: 670-677. 18. Veghelyi, P. V. 1939. Celiac disease initiated by giardiasis. Amer. J. Dis. Child. 57: 894-
9. Mortimer, D. C., P. I. Reed, M. Vidinili, and J. M. Finlay. 1964. The role of the upper gastrointestinal flora in the malabsorption syndrome. Canad. Med. Assn. J. 90: 559-564. 10. Uszynski, M. 1962. A case of hypogammaglobulinemia and secondary infantilism in a patient with chronic infection with lamblia intestinalis. Wiad. Parazyt. 8: 469-473. 11. Palumbo, P. J., H. H. Scudamore, and J. H. Thompson, Jr. 1962. Relationship of infestation with Giardia Lamblia to intestinalmalabsorption syndromes. Proc. Mayo Clin. 37: 589-598. 12. Hermans, P. E., K. A. Huizenga, H. N. Hoffman, A. L. Brown, Jr., and H. Markowitz. 1966. Dysgammaglobulinemia associated with nodular lymphoid hyperplasia of the small intestine. Amer. J. Med. 40: 78--89. 13. Ingram, V. 0., F. L. Rights, H. A. Khan, K. Hashimi, and K. Ansani. 1966. Diarrhea In children of West Pakistan : occurrence of bacterial and parasitic agents. Amer. J. Trop. Med. Hyg. 15: 743-750. 14. Ligny, G. 1961. Jejuno-ileites mixtes a lamblias staphylocoques. Arch. Mal. Appar. Dig. 50: 1162-2. 15. Mayoral, L. G., K. Tripathy, F. T. Garcia, and J. Ghitis. 1966. Intestinal malabsorption and parasitic disease: the role of protein malnutrition. Gastroenterology 50: 856--857. 16. Hartman, H. R., and F. A. Kyser. 1941.
Giardiasis and its treatment. J. A. M. A. 116: 2835-2839.
899. 19. Amini, F. 1963. Giardiasis and steatorrhoea. J. Trop. Med. Hyg. 66: 190-192. 20. Zamcheck, N., L. C. Hoskins, S. J. Winawer,
2!.
22.
23.
24.
25. 26.
S. A. Broitman, and L. S. Gottlieb. 1963. Histology and ultrastructure of the parasite and the intestinal mucosa in human giardiasis: effects of Antabrine therapy. Gastroenterology 44: 860. Takano, J ., and J. H. Yardley. 1965. Jejunal lesions in patients with giardiasis and malabsorption. An electron microscopic study. Bull. Hopkins Hosp. 116: 413-429. Cameron, A. H., R. Astley, M. Hallowell, A. B. Rawson, C. G. Miller, J . M. French, and D. V. Hubble. 1962. Duodenal-jejunal biopsy in the investigation of children with coeliac disease. Quart. J. Med. 31: 125-140. Durand, P . 1964. Lactose intolerance, p. 131132. In P. Durand [ed.], Disorders due to intestinal d efective carbohydrate di gestion and absorption. Pensiero Scientifico, Rome. Paulson, M., and J. Andrews. 1930. The incidence of human intestinal protozoa in duodenal aspirates. J. A. M. A. 94: 2063-2065. Anonymous. 1966. Giardiasis outbreak hits Aspen skiers. Mod. Med. 34 (No. 11): 32. Goodman, L. S., and A.Gilman. 1965. The pharmacological basis of therapeutics, Ed. 3, p. 1131. The MacMillan Company, New York.
MAXIMAL ACID SECRETION IN MAN In commenting on the paper of Makhlouf et al} Dr. Grossman 2 has again focused our attention on an important facet of gastric physiology-the assessment of the greatest output of hydrogen ions which the stomach of an individual can produce. Since Makhlouf suggests that "maximal secretory capacity" can be deduced mathematically, may I put in a word for an empirical approach to this index of gastric function? The synthesis of gastrin and polypeptide derivatives has made available new, powerful, gastric secretory stimulants which can be applied to the more rigorous evaluation
of gastric acid production in man. Using these hormones, it is possible in most individuals to define a level of gastric acid output which cannot be increased by increasing the dose of secretory stimulant. It is therefore possible to demonstrate, routinely, the greatest output of acid of which any stomach is capable, at least in response to these stimulants. It is at present a matter of conjecture whether a greater response might result from other gastric stimulants or combinations of stimulants. The ability of histamine or betazole to elicit maximal gastric secretion in human subjects is difficult to assess,