2
Note on the Value of Wolclman's Phenolphthalein Test for Gastro-lntestinal Lesions By L. J. NOTKIN, M.D., E. KIRSCH, M.D. and SAUL ALBERT, M.D. MONTREAL, CANADA A SIMPLE test for determining the presence of gastro-intestinal lesions was recently described by Woldman (1). This test is based on the author's belief that the free phenolphthalein found in the urine of patients after the ingestion of a relatively small amount of the substance, appears in the urine because it has passed freely through an area denuded of mucous membrane, such as occurs for instance in peptic ulcer. Because of the simplicity of the test and its obvious clinical value (if the claims of Woldman could be sub- stantiated) it was employed in a series of cases. The method described by Woldman was accurately followed. A dose of 0.1 Gin. of white phenolphthalein dissolved in 10 cc. 95% alcohol and diluted to 30 cc. with water, was administered to the subject of the test on a fast- ing stomach. No food or drink was taken for another hour. Specimens of the urine were obtained two and four hours later, and in cases of acute and chronic nephritis, cardiac failure, fever and dehydration also at six hours. The presence of free phenolphthalein was determined by the addition of 10% sodium hydrate in the usual manner. A total of 105 unselected cases were included in this investigation. Except for 12 prenatal cases from the Outpatient Department, they were ward patients and represented a cross-section of a general hospital popu- lation. Rather early in the investigation doubt was thrown on the accuracy of the test since its repetition in indi- vidual cases was not productive of constant results, gradations from negative to strongly positive being observed in the same cases in tests performed at ap- propriate intervals. The highest proportion of positives was obtained in the groups listed as (a) "Metabolic diseases" (3 cases of Diabetes Mellitus and 2 of Hyperthyroidism), and (b) "Extra-G.I. Tract Tumors" (including Hyper- nephroma, Lymphosarcoma of Abdominal Lymph Nodes and Giant Follicular Hyperplasia of Brill), namely 80%. The next highest proportion occurred in the group of active gastro-intestinal lesions, i.e. 69%. In this group of thirteen cases, four, or over 30%, gave negative results in tests repeated several times for confirmation. One of this group of four came to laparotomy at which advanced carcinoma of the stomach with extensive ulceration was found. The strongest positive reactions were obtained in a case of Giant Follicular Hyperplasia of Brill; at autopsy no break in the mucous membrane could anywhere be found. If the prenatal group, which may be considered "X-From the Department of Medicine, Jewish General Hospital, Montreal. essentially normal, and the group consisting of active gastro-intestinal lesions are excluded, the test is found to be positive in 46% of the cases. The high percentage of positive results may in part be accounted for by the fact that rhubarb, senna and cascara, in addition to certain other cathartics as well as phenolphthalein, impart a brown color to the urine which changes to red on addition of alkalies. Further- more, uro-rosein and uro-erythrin likewise impart a red color to an alkaline urine (2). It was, however, not considered worth while continuing with a variation of the test designed to eliminate uro-rosein and uro- Results of Woldman test in group of 105 cases No. of Po ~. Neg. Disease Group Cases W. Test W. Test Prenatal cases Cardiovascular Ulcer and Ca. Store. and Int. Other G.I. diseases Minor surgery and Orthopaedic Metabolic diseases Gynecological diseases Pulmonary diseases Extra-G.I. Tract tumors Miscellaneous 12 13 13 17 19 5 6 3 5 12 105 1 ( 8.3~;~ ) 5 (38.4%) 9 (69 (/t) 6 (35.3~) 7 (37 %) 4 (80 eft) 2 (33.3%) 1 (33.3e/~) 4 (80 %) 4 (33.3%) 43 (40.9 ~c~ ) 11 8 4 11 12 1 4 2 1 8 62 erythrin and to control the intake of substances likely to interfere with the accuracy of the test, because of the high proportion of negative results obtained in cases with active gastro-intestinal lesions. CONCLUSIONS 1. In a series of 105 cases representing a wide range of diseases, including those of the gastro-in- testinal tract, a large proportion gave a positive Wold- man test, i.e. over 40%. An even higher percentage is obtained (46%) if the groups consisting of gastro- intestinal lesions and the prenatal cases, totaling 25 cases, are excluded. These figures are entirely out of the realm of probability as representing the percent- age of ulcerative gastro-intestinal lesions in an un- selected group of cases in a general hospital. 2. In a number of cases in which the test was re- 365

Note on the value of woldman’s phenolphthalein test for gastro-intestinal lesions

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Page 1: Note on the value of woldman’s phenolphthalein test for gastro-intestinal lesions

Note on the Value of Wolclman's Phenolphthalein Test for Gastro-lntestinal Lesions

By

L. J. NOTKIN, M.D., E. KIRSCH, M.D. and

SAUL ALBERT, M.D. M O N T R E A L , C A N A D A

A SIMPLE test for determining the presence of gastro-intestinal lesions was recently described

by Woldman (1). This test is based on the author 's belief that the free phenolphthalein found in the urine of patients af ter the ingestion of a relatively small amount of the substance, appears in the urine because it has passed freely through an area denuded of mucous membrane, such as occurs for instance in peptic ulcer.

Because of the simplicity of the test and its obvious clinical value (if the claims of Woldman could be sub- stantiated) it was employed in a series of cases. The method described by Woldman was accurately followed. A dose of 0.1 Gin. of white phenolphthalein dissolved in 10 cc. 95% alcohol and diluted to 30 cc. with water, was administered to the subject of the test on a fast- ing stomach. No food or drink was taken for another hour. Specimens of the urine were obtained two and four hours later, and in cases of acute and chronic nephritis, cardiac failure, fever and dehydration also at six hours. The presence of free phenolphthalein was determined by the a d d i t i o n of 10% sodium hydrate in the usual manner.

A total of 105 unselected cases were included in this investigation. Except for 12 prenatal cases from the Outpatient Department, they were ward patients and represented a cross-section of a general hospital popu- lation.

Rather early in the investigation doubt was thrown on the accuracy of the test since its repetition in indi- vidual cases was not productive of constant results, gradations from negative to strongly positive being observed in the same cases in tests performed at ap- propriate intervals.

The highest proportion of positives was obtained in the groups listed as (a) "Metabolic diseases" (3 cases of Diabetes Mellitus and 2 of Hyperthyroidism), and (b) "Extra-G.I. Tract Tumors" (including Hyper- nephroma, Lymphosarcoma of A b d o m i n a l L y m p h Nodes and Giant Follicular Hyperplasia of Brill), namely 80%. The next highest proportion occurred in the group of active gastro-intestinal lesions, i.e. 69%. In this group of thirteen cases, four, or over 30%, gave negative results in tests repeated several times for confirmation. One of this group of four came to laparotomy a t w h i c h advanced carcinoma of the stomach with extensive ulceration was found. The strongest positive reactions were obtained in a case of Giant Follicular Hyperplasia of Brill; at autopsy no break in the mucous membrane could anywhere be found. I f the prenatal group, which may be considered

"X-From the D e p a r t m e n t of Medicine, J ewish General Hospi ta l , Montreal .

essentially normal, and the group consisting of active gastro-intestinal lesions are excluded, the test is found to be positive in 46% of the cases.

The high percentage of positive results may in part be accounted for by the fact that rhubarb, senna and cascara, in addition to certain other cathartics as well as phenolphthalein, impart a brown color to the urine which changes to red on addition of alkalies. Further- more, uro-rosein and uro-erythrin likewise impart a red color to an alkaline urine (2). I t was, however, not considered worth while continuing with a variation of the test designed to eliminate uro-rosein and uro-

Results of Woldman test in group of 105 cases

No. of Po ~. Neg. Disease Group Cases W. Test W. Test

P rena t a l cases

Cardiovascu la r

Ulce r and Ca. Store. and In t .

Other G.I. diseases

Minor su rge ry and Or thopaedic

Metabolic diseases

Gynecological diseases

P u l m o n a r y diseases

Ext ra -G. I . T r a c t t umors

Miscellaneous

12

13

13

17

19

5

6

3

5

12

105

1 ( 8.3~;~ )

5 (38 .4%)

9 (69 (/t)

6 ( 3 5 . 3 ~ )

7 (37 % )

4 (80 eft)

2 (33 .3%)

1 (33.3e/~)

4 (80 % )

4 (33 .3%)

43 (40.9 ~c~ )

11

8

4

11

12

1

4

2

1

8

62

erythrin and to control the intake of substances likely to interfere with the accuracy of the test, because of the high proportion of negative results obtained in cases with active gastro-intestinal lesions.

CONCLUSIONS

1. In a series of 105 cases representing a wide range of diseases, including those of the gastro-in- testinal tract, a large proportion gave a positive Wold- man test, i.e. over 40%. An even higher percentage is obtained (46%) if the groups consisting of gastro- intestinal lesions and the prenatal cases, totaling 25 cases, are excluded. These figures are entirely out of the realm of probability as representing the percent- age of ulcerative gastro-intestinal lesions in an un- selected group of cases in a general hospital.

2. In a number of cases in which the test was re- 365

Page 2: Note on the value of woldman’s phenolphthalein test for gastro-intestinal lesions

366 A M E R I C A N J O U R N A L OF D I G E S T I V E D I S E A S E S

peated several t imes at appropr ia te intervals, the results were inconstant, varying f rom negative to strongly positive.

3. Some of the cases giving the strongest reactions had no gastro-intest inal lesions; one such case came to autopsy.

4. In the group of cases represent ing active gastro- intestinal lesions, over 30% gave negative results.

5. This test does not t a k e i n t o consideration

certain substances other than phenolphthalein which give a red color in alkaline urine.

6. The Woldman phenolphthalein test does not constitute a test for the presence of gastro-intest inal lesions.

R E F E R E N C E S 1. Woldman, Edward E. : A Simple Test for Dete rmin ing the Presence

of Gast ro-Intes t inal Lesions. A m . J. Dig. Dis., 5:221, June , 1938. 2. Todd, J ames Campbell and Sauford, A r t h u r Hawley : Clinical Diag-

nosis by Labora to ry Methods. W. B. Saunders Co., Philadelphia, p. 79, 1935.

The Use of $ecretin as a Clinical Test of Pancreatic Function By

JOSEPH S. DIAMOND, M.D., S. A. SIEGEL, M.D., M. B. GALL, M.D. and

S. KARLEN, M.D. N E W YORK, N E W YORK

T HE study "of pure pancreatic juice has hi therto been possible only when the secretion was obtained

in the experimental animal through a fistula in the pancreatic duct, or occasionally in man in accidental post-operative pancreatic fistulas. All the earlier physi- ologic studies of the secretion of the gland by Claude Bernard, Bayliss and Starling, and Pavlov were made by introducing a cannula into the pancreatic duct.

In recent years McClure (1) and Myers (2) in this country and Christ iansen (3) in Denmark have carried on many clinical investigations in man. They studied the duodenal juices obtained through the tube and at tempted to evaluate pancreatic activity by studies of enzyme concentration. Pancreat ic stimu- lation was induced by the adminis trat ion of various single foods and admixture of foods introduced either into the stomach or intra-duodenally. Studies were made a t different periods of digestion f rom samples of duodenal juice. Inorganic substances such as water, hydrochloric acid, magnesium sulphate were also used as pancreatic stimulants.

While these studies have afforded a valuable insight into the enzyme response to the various food stimuli, it became apparent tha t the fai lure to obtain pure un- contaminated pancreatic juice gave rise to variable re- sults. The admixture of the acid chyme f rom the stomach, or the discharge of hydrochloric acid into the duodenum even in the fas t ing s tate lowers the pH of the duodenal juices by neutralizing the bicarbonate and inhibits the opt imum enzyme activity. These variable and inconstant results have rendered un- reliable the routine application of the clinical enzyme studies. Only as recent as 1934 a report by a com- mittee of the American Gastro-Enterological Asso- ciation on "A Survey of Enzyme Test" (4) revealed that only twenty-seven of its one hundred thirty-five members performed tests for one or more of the pan- creatic enzymes.

Since Bayliss and Starl ing in 1902 discovered the presence of secretin in the intestinal mucous mem- brane and described its specific effect upon the ex- ternal secretory cells of the pancreas, many at tempts

* F r o m the Sydenham Hospi ta l , New York. This work was made possible by the "Dr. Max P,,osenthal F u n d . " Submitted Apri l 12, 1939.

have been made to isolate the hormone and utilize It experimentally and clinically. Chiray, Salmon and Mercier (5) in 1926 used a secretin prepared accord- ing to a method by Pinan and Simonet. In 1934 ex- tensive studies were carried on in animal and man by Voegtlin, Greengard and Ivy (6), using a secretin prepared by Ivy. They obtained a definite increase in

"the output of pancreatic juice and enzymes a f t e r the intravenous administrat ion of secretin. In the i r series of twenty-two cases they felt, however, tha t the re- sults were of little clinical value, especially when a systemic reaction occurred following a repeated in- jection. ( Ivy has since reported the preparat ion of a crystalline secretin (7 ) ) . I t remained for the Swedish investigators, Hammars ten , Agren and Wilander (8, 9) to prepare secretin in a pure state. They have studied extensively its physiological and pharmacolo- gical propert ies in the cat and standardized it in units. Hammars ten , Agren, Lagerlof and Berglund (10, 11, 12) also carried on these studies in man and have re- ported a series of important clinical observations. They also at tempted to establish the normal limits of the response to secretin per given t ime and body weight. Utilizing the double tube method in collecting the secretion according to Lim, Matheson and Schlapp (13) they were able to obtain an uncontaminated pancreatic juice without interference of the gastr ic hydrochloric acid stimulus. Also by this method they were able to study for the first t ime clinically the bi- carbonate content of pancreatic juice in man.

Secretin* is an extract prepared f rom the small in- testines of the hog. I t is a whitish powder, readily soluble in water, stable in character and not affected by boiling. I t is a non-toxic, ant igen-free substance. I t has no effect upon the blood pressure and aside f rom an occasional, slight and temporary flushing of the face it produces no untoward effects.

The present report is based upon the s tudy of twenty-two cases consisting of fourteen normal indi- viduals who had no gastro-intest inal disturbances or any biliary or pancreatic disorders, and eight ab- normal cases. We have studied and tabulated the physiological response in the normal state. We have

*Ast ra , Sweden.