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Practical Office Procedures in Gastroenterology
Practical Office Procedures in Gastroenterology JOHN B. ALEXANDER, M.D. Assistant Professor of Clinical Medicine, University of Pennsylvania School of Medicine; Associate Physician, Pennsylvania Hospital; Associate Physician, The Benjamin Franklin Clinic, Philadelphia
GASTROEN'fEROLOGY, like most of the divisions of clinical medicine, leans heavily upon laboratory data for diagnostic and therapeutic guidance. Many of the laboratory procedures applicable to gastroenterology are complicated and require the supervision of clinical pathologists and chemists. A few tests in common use, however, are well within the capabilities of an office laboratory and it is from this group that the following studies have been selected for presentation as practical office procedures: (1) stool examination for occult blood; (2) stool examination for motile amebae; (:3) urine examination for bile pigment; (4) gastric analysis, tube and tubeless. The discussion of these procedures which follows is not intende( to take the place of a laboratory manual but is an attempt to comment upon the nature of the tests, the data they furnish and their place in the practice of medicine.
STOOL EXAMINATION FOR OCCULT BLOOD
The Tests
The benzidine, guaiac and orthotolidine tests are all reliable and relatively simple. Numerous techniques have been devised for performing these tests and many ways of preparing the reagent solutions and processing the fecal specimen have been proposed.!' 2, 3 Since it would be impossible to choose one best method from this number of excellent methods, simplicity will probably be the best guide. Accordingly, for office use, it is suggested that the feces be smeared in a thin layer on filter paper and that solutions of benzidine dihydrochloride and of gum guaiac be prepared and used as detailed in Ham's excellent syllabus. 2 For greater convenience in performing the guaiac test a reagent paper tape with developer solution (Hemoccult) has recently appeared on the market. For perhaps the greatest simplicity there is an orthotolidine
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reagent tablet (Hematest) which reduces the entire procedure to the application of water to the tablet and specimen with a medicine dropper. All of these tests produce a blue color in the presence of hemoglobin. The sensitivity of a given test depends on the technique but, in general, benzidine and orthotolidine are more sensitive than guaiac. A test is regarded as positive in most methods if it produces a strong blue color within 60 seconds. No col or, faint color and slow appearance are read as negative. Sources of Error
Misleading results may stem from any of the tests through false positive and false negative reactions and from the fact that blood may reach the feces from sources other than lesions of the gastrointestinal tract. False reactions are due to defective, deteriorated or contaminated test materials and, although the causes may not be discoverable, the occurrence of such reactions can readily be detected. False positive reactions are demonstrated by performing the test in blank, that is, without the feces, and false negative reactions by performing the test with blood as a positive control (Ham suggests one drop of blood in 50 milliliters of water). It cannot be too strongly emphasized that all test materials, including tablets, must be put through blank and positive control trials at appropriate intervals and that liquid solutions should be tested with positive control daily. Even though the tests are giving true results, misleading positive reactions can result from extraneous sources of blood in the food or from bleeding about the mouth or anus. Patients should be asked not to eat meat, fish or fowl for three days before collection of specimens. Bleeding in the vicinity of the mouth may come from the gums, tooth sockets, oral sores, abrasion by dentures, nosebleed or hemoptysis; anal sources include hemorrhoids, fissures and excoriation by enema tubes. Interpretation
If the known sources of error have been eliminated, a positive reaction for blood in feces is indicative of a bleeding lesion in the digestive tract. In the absence of anemia or other suggestive findings, however, one positive result does not necessarily call for full investigation but rather for the testing of additional specimens. If two or more specimens are positive, complete proctoscopic and x-ray examinations are in order and must often include the small intestine and biliary tract. A negative test for occult blood carries less authority than a positive one, but repeatedly negative results argue strongly against the existence of a bleeding lesion. Since even gastrointestinal cancers sometimes fail to produce occult blood, the decision as to the need for further studies
Practical Office Procedures in Gastroenterology
1517
hinges entirely on the clinical facts and should not be too strongly influenced by negative stool examinations. The Need for Quantitative Tests
As implied above, the data provided by the ordinary tests for occult blood are quantitative only in the crudest sense of the word-strongly or weakly positive or negative--and there is no way of reducing the result to an expression of the number of grams of hemoglobin or milliliters of blood per 24 hours. Some of the obstacles in the way of a quantitative test are variations between batches of benzidine, deterioration of solutions, fecal coating of particles of hemoglobin and possible degradation of the hemoglobin molecule by digestive enzymes or by bacterial action. A technique for overcoming these difficulties has recently been published by Ebaugh and Beeken. 3R They employ a quantitative benzidine test on feces prepared by emulsification in a Waring Blendor. The amount of hemoglobin is measured by photospectrometric comparison with a prepared hemoglobin standard. This test is obviously not for the office laboratory, but it represents a major effort to improve and refine the testing of occult blood in feces. STOOL EXAMINATION FOR AMEBAE
The vegetative or motile form of Endameba histolytic a can be found only in freshly collected liquid feces or in fresh material swabbed or scraped from the rectal mucosa during proctoscopy. Since the freshness of the sample is such an important factor, the search for these parasites must be done in the office laboratory unlesR other facilities are available very near by. The procedure is simple: the feces are examined on a slide by low power and high dry objectives. The parasite is recognized by its active motility, its pseudopodia and its ingested erythrocytes. If the material is examined within 30 minutes of collection, no warming is necessary. Otherwise the specimen should be maintained at body temperature. It is beyond the scope of this presentation to furnish the information needed to establish positive identification of E. histolytic a and to differentiate it from other intestinal amebae. There are descriptions in laboratory and parasitology texts, but it is essential that the physician be shown a few positive specimens by a person qualified in this field. URINE EXAMINATION FOR BILE PIGMENT
Foam Test
A urine specimen containing excessive amounts of bile pigment (bilirubin) usually has a dark yellow-brown color and if shaken produces
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a rich foam with a distinct yellow color in daylight. Other dark urines, with few exceptions, produce white foam. This test, requiring no reagents, is ideally suited to office use. It is seldom misleading, but nevertheless good practice requires a more specific confirmatory test. Specific Tests for Bilirubinuria Texts give several methods of identifying bile pigment in urine, and most of these tests are simple enough to be performed in the office. Smith's test, using tincture of iodine in alcohol, and Gmelin's test, using yellow nitric acid, are very simple and quick. Harrison's test, employing Fouchet's reagent and barium chloride solution, is a little more elaborate but still usable. The only objection to any of them is the inconvenience of making up the necessary solutions and in Gmelin's test the danger of having strong nitric acid in the office. The most trouble-free method now available employs a reagent tablet (Ictotest), which reduces the test to a medicine dropper procedure. It is reported 4 that the sensitivity of this tablet test is superior to that of the older standard tests. Interpretation The demonstration of bilirubin in the urine offers strong confirmatory evidence when jaundice is suspected but not certain. This finding also signifies that the jaundice is obstructive or hepatocellular rather than hemolytic or acholuric. Negative tests for bilirubinuria do not rule out the presence of jaundice or biliary disease since the excretion of hile pigment is unpredictable and capricious even in the presence of ohvious jaundice. GASTRIC ANALYSIS
Gastric analysis is ordinarily employed to measure the capacity of the stomach to secrete hydrochloric acid. This capacity is usually estimated by the titration of samples of gastric juice obtained by tube, a method which allows roughly quantitative results and which has the added advantage of permitting the gastric juice to be inspected and measured. An alternate method is a tubeless dye-resin urinary excretion test capable of giving qualitative information concerning acid secretion by the stomach. Both tests are commonly done in physicians' offices. Tube Analysis Many highly satisfactory techniques of analysis have been proposed and a variety of test meals and stimulants have found favor from time to time. It is suggested that for office use the histamine analysis be used routinely (except in patients who are sensitive to histamine) and that the procedure follow the general plan of the "fractional" analysis as given in many manuals. The essential step is the testing of the fasting
Practical Office Procedures in Gastroenterology
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gastric contents with Topfer's reagent to determine whether free acid is present. If the red color appears, denoting free acid, the analysis may be ended (although many physicians prefer to continue it). If Topfer's reagent turns yellow, indicating no free acid, histamine or preferably Histalog (betazole HCI) should be injected and additional samples tested for a two-hour period or until free acid is demonstrated in one of the samples. As a confirmatory step, any sample of gastric juice (fasting or poststimulation) which gives qualitative evidence of free acidity when tested with Topfer's reagent may also be titrated to determine whether the amount of free HCI is borderline (2 to 5 units) or abundant. Ideally, this titration should be done before withdrawal of the tube, since borderline values usually call for the use of Histalog or the collection of more samples. TERMS. The terms used in reporting the findings of gastric analysis deserve brief comment here. "Free" acidity is said to be present in gastric juice when the pH of the juice is 3.0 or lower. Topfer's reagent has long been recognized as the standard indicator because of its red color at pH 2.8, very close to the accepted value for free acidity. In titration with sodium hydroxide solution, Topfer's reagent turns yellow at pH 4.0 to 5.0, still close to free acidity standards. The concept of "free" acidity, though arbitrary, corresponds closely with the acidity required for the proteolytic activity of pepsin, which is optimal at pH 1.5 to 2.5. 6 The term "combined" acidity is also well established by custom. Combined acidity is determined by titration to the point where the indicator phenolphthalein turns pink, representing approximately pH 8.5. Although "combined" acidity has no clear-cut clinical meaning, its value provides confirmatory information in achlorhydria, showing how far the sample falls short of having "free" acidity (or pH 3.0). The third term in common use is "total" acidity, the sum of "free" and "combined" acidity values. It has no special clinical significance. These three terms are useful principally because they are timehonored and because their ranges of values are familiar to all physicians. There appears to be very little likelihood that the profession will abandon the titration of gastric acidity in the foreseeable future. An indicator tape (Hydrion), however, has appeared on the market in recent years and is capable of registering pH values from 1.0 to 6.0. It can thereby show the presence of "free" acidity without resort to titration. 2 • 6 It remains to be seen whether this product or ones like it can gain the confidence of physicians as the old methods have. SOURCES OF ERROR. Gastric analysis by tube is usually reliable and trouble-free. A few patients, of course, have difficulty in swallowing the tube and some fail completely. The gastric acidity may be reduced by swallowed saliva or may be neutralized by bile regurgitated into the stomach from the duodenum. Bile in gastric juice may be recognized by
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its green or yellow color. Lastly, some normal stomachs empty so rapidly as to prevent the aspiration of satisfactory samples; this effect is frequently encountered after gastrectomy or gastroenterostomy. Tubeless Gastric Analysis
Tubeless analysis is now accomplished by the introduction into the stomach of a dye-resin complex (Diagnex Blue)7 so constituted that the complex breaks up in the presence of "free" acidity in the stomach, releasing a blue dye which is absorbed by the intestine. Following absorption, the dye is carried in the blood and is excreted by the kidney. It follows that if dye can be demonstrated in the urine hydrochloric acid can be assumed to be present in the stomach. Conversely, the absence of the dye from the urine proves the absence of hydrochloric acid from the stomach. Like tube analysis, the tubeless method can be combined with histamine or Histalog stimulation to bring out the full capability of the gastric mucosa. 8 The identification of the dye in urine is simple when generous amounts are present, indicating free acidity in the stomach. When dye is not found at first look, it is necessary to acidify, boil and cool the urine specimen according to exact instructions before proof of achlorhydria can be established. SOURCES OF ERROR. As a rule, tubeless analysis is entirely satisfactory within its limitations. If the patient under study has a disease state capable of interfering with the absorption, transport or elimination of the dye, then reduced amounts of dye will appear in the urine and correspondingly low values will be determined for the gastric acidity. Disorders which may cause such erroneous low values are malabsorption states, diarrhea, emesis, liver disease, renal disease, urinary obstructiotJ and congestive heart failure. Uses of Gastric Analysis
Gastric analysis has only two principal uses in clinical medicine, namely, to determine the presence of achlorhydria in the study of gastric cancer and of pernicious anemia and to demonstrate the presence of free acidity in the study of peptic ulcer disease. In neither circumstance can analysis furnish a diagnosis, but the data it offers can have very influential confirmatory value, especially in the always vexing problem of the gastric ulcer which may be benign or malignant. The situations in which knowledge of the gastric acidity can influence diagnosis are as follows: (1) If free acidity is not found, gastric ulcer is assumed to be malignant; peptic ulcer disease cannot occur; pernicious anemia is possible. Conversely, (2) if free acidity is found, gastric ulcer may be benign and short trial of a medical regimen is justified; peptic ulcer disease can occur; pernicious anemia can be ruled out. Both tube and tubeless methods can accomplish these primary
Practical Office Procedures in Gastroenterology
1521
objectives, and at times it may be reassuring to have both kinds of analysis in the same case. Any doubt as to choice of method, however, should be resolved in favor of the tube in view of the directness of its approach, its quantitative results and the opportunity it provides for the discovery of gastric retention or hemorrhage by first-hand inspection and measurement of the gastric juice. REFERENCES 1. Todd, J. C., Sanford, A. H. and Wells, B. B.: Clinical Diagnosis by Laboratory Methods. 12th ed. Philadelphia, W. B. Saunders Company, 1953. 2. Ham, T. H.: A Syllabus of Laboratory Examinations in Clinical Diagnosis. Cambridge, Mass., Harvard University Press, 1950. 3. Smith, R. L.: Faecal Occult Blood Tests without Dietary Restrictions. Brit. M. J. 1: 1336, 1958. 3a. Ebaugh, F. G., Jr. and Beeken, W. L.: Quantitative Measurement of Gastrointestinal Blood Loss. J. Lab. & Clin. Med. 53: 777, 1959. 4. Bleyer, J. M. and Steigmann, F.: Old and New Tests for Biliruhin in the Urine. Am. J. Digest. Dis. 3: 947, 1958. 5. Bodanski, O. and Bodanski, M.: Biochemistry of Disease. 2nd ed. New York, The Macmillan Company, 1952. 6. Sippy, I. H. and Fitzsimmons, E. .I.: Measurement of Free Acid in Gastric Juice by Means of Indicator Paper. .I.A.M.A. 170: 1157, 1959. 7. Council on Drugs: Azuresin (Diagnex Blue). J. A.M.A. 170: 1550, 1959. 8. Galambos. J. T. and Kirsner, J. B.: Tubeless Ga,tric Analysis. Arch. Int. Med. 96: 752, 1955.
330 South 9th Street Philadelphia 7, Pennsylvania
GASTROEN'fEROLOGY, like most of the divisions of clinical medicine, leans heavily upon laboratory data for diagnostic and therapeutic guidance. Many of the laboratory procedures applicable to gastroenterology are complicated and require the supervision of clinical pathologists and chemists. A few tests in common use, however, are well within the capabilities of an office laboratory and it is from this group that the following studies have been selected for presentation as practical office procedures: (1) stool examination for occult blood; (2) stool examination for motile amebae; (:3) urine examination for bile pigment; (4) gastric analysis, tube and tubeless. The discussion of these procedures which follows is not intende( to take the place of a laboratory manual but is an attempt to comment upon the nature of the tests, the data they furnish and their place in the practice of medicine.
STOOL EXAMINATION FOR OCCULT BLOOD
The Tests
The benzidine, guaiac and orthotolidine tests are all reliable and relatively simple. Numerous techniques have been devised for performing these tests and many ways of preparing the reagent solutions and processing the fecal specimen have been proposed.!' 2, 3 Since it would be impossible to choose one best method from this number of excellent methods, simplicity will probably be the best guide. Accordingly, for office use, it is suggested that the feces be smeared in a thin layer on filter paper and that solutions of benzidine dihydrochloride and of gum guaiac be prepared and used as detailed in Ham's excellent syllabus. 2 For greater convenience in performing the guaiac test a reagent paper tape with developer solution (Hemoccult) has recently appeared on the market. For perhaps the greatest simplicity there is an orthotolidine
1515
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ALEXANDER
reagent tablet (Hematest) which reduces the entire procedure to the application of water to the tablet and specimen with a medicine dropper. All of these tests produce a blue color in the presence of hemoglobin. The sensitivity of a given test depends on the technique but, in general, benzidine and orthotolidine are more sensitive than guaiac. A test is regarded as positive in most methods if it produces a strong blue color within 60 seconds. No col or, faint color and slow appearance are read as negative. Sources of Error
Misleading results may stem from any of the tests through false positive and false negative reactions and from the fact that blood may reach the feces from sources other than lesions of the gastrointestinal tract. False reactions are due to defective, deteriorated or contaminated test materials and, although the causes may not be discoverable, the occurrence of such reactions can readily be detected. False positive reactions are demonstrated by performing the test in blank, that is, without the feces, and false negative reactions by performing the test with blood as a positive control (Ham suggests one drop of blood in 50 milliliters of water). It cannot be too strongly emphasized that all test materials, including tablets, must be put through blank and positive control trials at appropriate intervals and that liquid solutions should be tested with positive control daily. Even though the tests are giving true results, misleading positive reactions can result from extraneous sources of blood in the food or from bleeding about the mouth or anus. Patients should be asked not to eat meat, fish or fowl for three days before collection of specimens. Bleeding in the vicinity of the mouth may come from the gums, tooth sockets, oral sores, abrasion by dentures, nosebleed or hemoptysis; anal sources include hemorrhoids, fissures and excoriation by enema tubes. Interpretation
If the known sources of error have been eliminated, a positive reaction for blood in feces is indicative of a bleeding lesion in the digestive tract. In the absence of anemia or other suggestive findings, however, one positive result does not necessarily call for full investigation but rather for the testing of additional specimens. If two or more specimens are positive, complete proctoscopic and x-ray examinations are in order and must often include the small intestine and biliary tract. A negative test for occult blood carries less authority than a positive one, but repeatedly negative results argue strongly against the existence of a bleeding lesion. Since even gastrointestinal cancers sometimes fail to produce occult blood, the decision as to the need for further studies
Practical Office Procedures in Gastroenterology
1517
hinges entirely on the clinical facts and should not be too strongly influenced by negative stool examinations. The Need for Quantitative Tests
As implied above, the data provided by the ordinary tests for occult blood are quantitative only in the crudest sense of the word-strongly or weakly positive or negative--and there is no way of reducing the result to an expression of the number of grams of hemoglobin or milliliters of blood per 24 hours. Some of the obstacles in the way of a quantitative test are variations between batches of benzidine, deterioration of solutions, fecal coating of particles of hemoglobin and possible degradation of the hemoglobin molecule by digestive enzymes or by bacterial action. A technique for overcoming these difficulties has recently been published by Ebaugh and Beeken. 3R They employ a quantitative benzidine test on feces prepared by emulsification in a Waring Blendor. The amount of hemoglobin is measured by photospectrometric comparison with a prepared hemoglobin standard. This test is obviously not for the office laboratory, but it represents a major effort to improve and refine the testing of occult blood in feces. STOOL EXAMINATION FOR AMEBAE
The vegetative or motile form of Endameba histolytic a can be found only in freshly collected liquid feces or in fresh material swabbed or scraped from the rectal mucosa during proctoscopy. Since the freshness of the sample is such an important factor, the search for these parasites must be done in the office laboratory unlesR other facilities are available very near by. The procedure is simple: the feces are examined on a slide by low power and high dry objectives. The parasite is recognized by its active motility, its pseudopodia and its ingested erythrocytes. If the material is examined within 30 minutes of collection, no warming is necessary. Otherwise the specimen should be maintained at body temperature. It is beyond the scope of this presentation to furnish the information needed to establish positive identification of E. histolytic a and to differentiate it from other intestinal amebae. There are descriptions in laboratory and parasitology texts, but it is essential that the physician be shown a few positive specimens by a person qualified in this field. URINE EXAMINATION FOR BILE PIGMENT
Foam Test
A urine specimen containing excessive amounts of bile pigment (bilirubin) usually has a dark yellow-brown color and if shaken produces
1518
JOHN
B.
ALEXANDER
a rich foam with a distinct yellow color in daylight. Other dark urines, with few exceptions, produce white foam. This test, requiring no reagents, is ideally suited to office use. It is seldom misleading, but nevertheless good practice requires a more specific confirmatory test. Specific Tests for Bilirubinuria Texts give several methods of identifying bile pigment in urine, and most of these tests are simple enough to be performed in the office. Smith's test, using tincture of iodine in alcohol, and Gmelin's test, using yellow nitric acid, are very simple and quick. Harrison's test, employing Fouchet's reagent and barium chloride solution, is a little more elaborate but still usable. The only objection to any of them is the inconvenience of making up the necessary solutions and in Gmelin's test the danger of having strong nitric acid in the office. The most trouble-free method now available employs a reagent tablet (Ictotest), which reduces the test to a medicine dropper procedure. It is reported 4 that the sensitivity of this tablet test is superior to that of the older standard tests. Interpretation The demonstration of bilirubin in the urine offers strong confirmatory evidence when jaundice is suspected but not certain. This finding also signifies that the jaundice is obstructive or hepatocellular rather than hemolytic or acholuric. Negative tests for bilirubinuria do not rule out the presence of jaundice or biliary disease since the excretion of hile pigment is unpredictable and capricious even in the presence of ohvious jaundice. GASTRIC ANALYSIS
Gastric analysis is ordinarily employed to measure the capacity of the stomach to secrete hydrochloric acid. This capacity is usually estimated by the titration of samples of gastric juice obtained by tube, a method which allows roughly quantitative results and which has the added advantage of permitting the gastric juice to be inspected and measured. An alternate method is a tubeless dye-resin urinary excretion test capable of giving qualitative information concerning acid secretion by the stomach. Both tests are commonly done in physicians' offices. Tube Analysis Many highly satisfactory techniques of analysis have been proposed and a variety of test meals and stimulants have found favor from time to time. It is suggested that for office use the histamine analysis be used routinely (except in patients who are sensitive to histamine) and that the procedure follow the general plan of the "fractional" analysis as given in many manuals. The essential step is the testing of the fasting
Practical Office Procedures in Gastroenterology
1519
gastric contents with Topfer's reagent to determine whether free acid is present. If the red color appears, denoting free acid, the analysis may be ended (although many physicians prefer to continue it). If Topfer's reagent turns yellow, indicating no free acid, histamine or preferably Histalog (betazole HCI) should be injected and additional samples tested for a two-hour period or until free acid is demonstrated in one of the samples. As a confirmatory step, any sample of gastric juice (fasting or poststimulation) which gives qualitative evidence of free acidity when tested with Topfer's reagent may also be titrated to determine whether the amount of free HCI is borderline (2 to 5 units) or abundant. Ideally, this titration should be done before withdrawal of the tube, since borderline values usually call for the use of Histalog or the collection of more samples. TERMS. The terms used in reporting the findings of gastric analysis deserve brief comment here. "Free" acidity is said to be present in gastric juice when the pH of the juice is 3.0 or lower. Topfer's reagent has long been recognized as the standard indicator because of its red color at pH 2.8, very close to the accepted value for free acidity. In titration with sodium hydroxide solution, Topfer's reagent turns yellow at pH 4.0 to 5.0, still close to free acidity standards. The concept of "free" acidity, though arbitrary, corresponds closely with the acidity required for the proteolytic activity of pepsin, which is optimal at pH 1.5 to 2.5. 6 The term "combined" acidity is also well established by custom. Combined acidity is determined by titration to the point where the indicator phenolphthalein turns pink, representing approximately pH 8.5. Although "combined" acidity has no clear-cut clinical meaning, its value provides confirmatory information in achlorhydria, showing how far the sample falls short of having "free" acidity (or pH 3.0). The third term in common use is "total" acidity, the sum of "free" and "combined" acidity values. It has no special clinical significance. These three terms are useful principally because they are timehonored and because their ranges of values are familiar to all physicians. There appears to be very little likelihood that the profession will abandon the titration of gastric acidity in the foreseeable future. An indicator tape (Hydrion), however, has appeared on the market in recent years and is capable of registering pH values from 1.0 to 6.0. It can thereby show the presence of "free" acidity without resort to titration. 2 • 6 It remains to be seen whether this product or ones like it can gain the confidence of physicians as the old methods have. SOURCES OF ERROR. Gastric analysis by tube is usually reliable and trouble-free. A few patients, of course, have difficulty in swallowing the tube and some fail completely. The gastric acidity may be reduced by swallowed saliva or may be neutralized by bile regurgitated into the stomach from the duodenum. Bile in gastric juice may be recognized by
1520
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ALEXANDER
its green or yellow color. Lastly, some normal stomachs empty so rapidly as to prevent the aspiration of satisfactory samples; this effect is frequently encountered after gastrectomy or gastroenterostomy. Tubeless Gastric Analysis
Tubeless analysis is now accomplished by the introduction into the stomach of a dye-resin complex (Diagnex Blue)7 so constituted that the complex breaks up in the presence of "free" acidity in the stomach, releasing a blue dye which is absorbed by the intestine. Following absorption, the dye is carried in the blood and is excreted by the kidney. It follows that if dye can be demonstrated in the urine hydrochloric acid can be assumed to be present in the stomach. Conversely, the absence of the dye from the urine proves the absence of hydrochloric acid from the stomach. Like tube analysis, the tubeless method can be combined with histamine or Histalog stimulation to bring out the full capability of the gastric mucosa. 8 The identification of the dye in urine is simple when generous amounts are present, indicating free acidity in the stomach. When dye is not found at first look, it is necessary to acidify, boil and cool the urine specimen according to exact instructions before proof of achlorhydria can be established. SOURCES OF ERROR. As a rule, tubeless analysis is entirely satisfactory within its limitations. If the patient under study has a disease state capable of interfering with the absorption, transport or elimination of the dye, then reduced amounts of dye will appear in the urine and correspondingly low values will be determined for the gastric acidity. Disorders which may cause such erroneous low values are malabsorption states, diarrhea, emesis, liver disease, renal disease, urinary obstructiotJ and congestive heart failure. Uses of Gastric Analysis
Gastric analysis has only two principal uses in clinical medicine, namely, to determine the presence of achlorhydria in the study of gastric cancer and of pernicious anemia and to demonstrate the presence of free acidity in the study of peptic ulcer disease. In neither circumstance can analysis furnish a diagnosis, but the data it offers can have very influential confirmatory value, especially in the always vexing problem of the gastric ulcer which may be benign or malignant. The situations in which knowledge of the gastric acidity can influence diagnosis are as follows: (1) If free acidity is not found, gastric ulcer is assumed to be malignant; peptic ulcer disease cannot occur; pernicious anemia is possible. Conversely, (2) if free acidity is found, gastric ulcer may be benign and short trial of a medical regimen is justified; peptic ulcer disease can occur; pernicious anemia can be ruled out. Both tube and tubeless methods can accomplish these primary
Practical Office Procedures in Gastroenterology
1521
objectives, and at times it may be reassuring to have both kinds of analysis in the same case. Any doubt as to choice of method, however, should be resolved in favor of the tube in view of the directness of its approach, its quantitative results and the opportunity it provides for the discovery of gastric retention or hemorrhage by first-hand inspection and measurement of the gastric juice. REFERENCES 1. Todd, J. C., Sanford, A. H. and Wells, B. B.: Clinical Diagnosis by Laboratory Methods. 12th ed. Philadelphia, W. B. Saunders Company, 1953. 2. Ham, T. H.: A Syllabus of Laboratory Examinations in Clinical Diagnosis. Cambridge, Mass., Harvard University Press, 1950. 3. Smith, R. L.: Faecal Occult Blood Tests without Dietary Restrictions. Brit. M. J. 1: 1336, 1958. 3a. Ebaugh, F. G., Jr. and Beeken, W. L.: Quantitative Measurement of Gastrointestinal Blood Loss. J. Lab. & Clin. Med. 53: 777, 1959. 4. Bleyer, J. M. and Steigmann, F.: Old and New Tests for Biliruhin in the Urine. Am. J. Digest. Dis. 3: 947, 1958. 5. Bodanski, O. and Bodanski, M.: Biochemistry of Disease. 2nd ed. New York, The Macmillan Company, 1952. 6. Sippy, I. H. and Fitzsimmons, E. .I.: Measurement of Free Acid in Gastric Juice by Means of Indicator Paper. .I.A.M.A. 170: 1157, 1959. 7. Council on Drugs: Azuresin (Diagnex Blue). J. A.M.A. 170: 1550, 1959. 8. Galambos. J. T. and Kirsner, J. B.: Tubeless Ga,tric Analysis. Arch. Int. Med. 96: 752, 1955.
330 South 9th Street Philadelphia 7, Pennsylvania