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Studies in absorption of undigested protein in human beings
STUDIES
IN ABSORPTION
OF UNDIGESTED
HUMAN VTIT.
ABSORPTION
FROM
THE
OF ABSORPTION
GRAY,
M.D.,
IN
BEINGS
RHCTUM
AND
A
COMPARATIVE
ORAL, DUODENAL,, ADMINISTRATIONS
FOLLOWING
RECTAL IRVING
PROTEIN
AND
MATTHEW
WALZER,
STUDY
AND
M.D.
N. Y.
BROOKLYN,
N PREVIOUS communications the results of studies on the absorption of undigested peanut protein following oral1 and intraduodena12 administrations were reported. It was found that, following intraduodenal feeding, absorption of the peanut antigen was more rapid by several minutes than that following its oral consumption. It was also observed that, in the pres’ence of gastric hyperacidity, the absorption of the antigen was retarded, while in hypoacidity it was accelerated. This obtained, not only following the oral intake of ant,igen, but even when it was administered directly into the duodenum. The present communication deals with the absorption of peanut antigen following its introduction into the rectum. Sussman, Davidson, and Walzer3 had at an earlier date studied the absorption of egg protein from the rectum in a small series of adults. They demonstrated that the direct technique for demonstrating the absorption of unaltered protein which had been employed with oral administration* could be satisfactorily applied in rectal studies. Smyth and Stallings5 at a later date successfully used this technique in a similar study on infants and children. The technique employed in the present study has been described in detail in previous, communications and will be briefly summarized here. The subject to be studied was kept, for forty-eight hours on a diet from which all nuts were carefully excluded. He was then passively locally sensitized to peanut by an intracutaneous injection of human serum obtained from a8patient whose serum showed a, high reagin titer for this antigen. Clinically this patient was extremely sensitive to peanut and showed a very marked cutaneous reaction to a skin test with it. One-twentieth cubic centimeter of a 1 :lO dilution of this serum was injected intracutaneously in the forearm. On the following morning, without any special preliminary preparation of the subject, the peanut meal, consisting of 10 Cm. of raw ground peanuts in 20 cc. of water, was introduced by tube into the rectum. The sensitized cutaneous site was then kept under observation. The onset of a
I
From
Read Brooklyn,
the
Allergy
at the Nov.
Division
semiannual 5. 1936.
of
meeting
the
Jewish
Hospital
of the
Allergy
24b
Of Brooklyn.
Division
of the
Jewish
Hospital
of
246
THE
JOURNAL
OF
ALLERGY
reaction at this site, characterized by erythema, pruritus, formation, heralded the entrance of the peanut into the The interval between the int,roduction of the meal and the of the erythema at the sensitized site was considered the time for that person. TABLE ,Srhrxmv
OF STVDIES
or RECTAL (THIRTY-ONE
(‘ASE NO. 1oti I IO 113 114 123
AGE
SEX
38
M F M *Al
128 129 lU2 103 104
34 ?I 53 38 27 43 27 29 61 37 3“0 53 40 49 30 31 48 37 56 39
IO’S
53
F
109 Ill 1 I6 118
62 30 56 23 55
A9 F AI F
54 46 56 30
F M F F
101 105 107
112 115 II7 II9 121 12"
1 ?(i 127
I"0
124 125 130 131
_-
F A4
M E F M F M M
M M
F A4 F F
F
F
-
DIAGNOSIS Cholelithiasis Cholecystitis Colitis (mucous) Gastric neurosis Chronic cholecystitis IDuodenal ulcer Gastric ulcer Colitis Duodenal ulcer Gastric neurosis Duodenal ulcer Chronic eholecystitis Duodenal ulcer Gastric neurosis Gastric ulcer Gastric neurosis Gastric ulcer Duodenal ulcer Chronic cholecystitis Cholelithiasis Postoperative gall b der disease Ca,rcinomatous ulcer stomach Visceroptosis Cholelithiasis Colitis Visceroptosis Postoperative gall b der disease Chronic cholelithiasis Gastric neurosis Chronic cholec~ystitis Colitis
and wheal circulation. appearance absorption
I ABSORPTION
OF PEANUT
ANTIGEN
Casts)
-___DEGREE OF GASTRIC ACIDITY Normal Normal Normal Normal Normal
Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. ____HYPE. HYPE. Hypo.
iBSORPTION TIME IN MINUTES
32 I5 17 I6 I3 14 I4 26 18 36 16 I8 I5 17 23 2 28 13 10 20
Hypo.
22
HYPE. HYPE. Hypo. HYPE. Hype.
21 23 18 13 I9
Hypo. HYPE. HYPE. Hypo. zrage for
E
GROUP hvERAGE IN hlINUTES
11 18 I6 I5 ire Series
18.6
--
21.4
16.8 19.0
The subjects, employed in this study were adults of both Sexes, varying in age from 21 to 62 years, who suffered with various organic and functional disturbances8 of the gastrointestinal tract. The final diagIIosis iIz each case, determined after careful investigation, is listed in Table I. As in previous studies, the cases were roughly divided into three groups according to the degree of gastric acidity. They were designated as cases with hyperacidity, normal acidity, or hypoacidity, according to the commonly accepted standards which were outlined in detail in previous commnnications.l2 Atopic patients mere excluded from the study.
GRAY
AND
WALTZER,:
ABSQRPTION
OF
UNDIGEmSTXD
247
PROTEIN
Following rectal administration of the peanut meal, the absorption rates for the thirty-one cases in this series varied from 10 to 36 minutes. The average for the entire group was 19 minutes. The results of the earlier studies” on egg absorption from the rectum had suggested that the rectal absorption rate might be influenced by the degree of gastric acidity. This impression was confirmed in the present study. It mill be noted from the data presented in Table I that, in the five cases with normal acidity, the average absorption rate was 18.6 minutes. In the thirteen cases with hyperacidity, the average rate was 21.4 minutes, which was somewhat slower than the normal. For the thirteen cases with hypoacidity, the average absorption rate was 16.8, which was more rapid than the normal. TABLE CO~PARATIBE
STVDY OF ABSORPTION RATES ,IDnlINISTRATIONS OP PEAiYl;T
__~ CASE NO.
AGE 34
SEX
--
F
71 72 74 75 iA
47 39 27 RG
M M E M
77 78 79 80 81
“9 56 28 18 62
M F F F M
82 83 84 85
28 31 5G 26
F
-
E9 M F
II
AFTER
THE
PKOTEIPi
DIAGNOSIS
Chronic cholelithiasis Pyloric ulcer Duodenal ulcer Colitis Ulcerative colitis ant1 chronic proctosigmoiditis Duodenal ulcer Arteriosclerosis Chronic cholecystitis Migraine Carcinoma of colon (sigmoid 1 Chronic cholecystitis Duodenal ulcer Chronic gastritis /Gastric neurosis
ORAL, I)UODENAL, IN F'OI-RTEEx CASES
RMTAT,
AHSORPTION TIME INUTES
DEGREE OF GASTRIC ACIDITY
ORAL --. 18
Normal Hyper. Hyper. HYPE. Normal
Hyper. Normal Normal Normal HYPE.
-1
,S
-
I LECTAI, ~-
1f.i
16
23 25 22 20
23 28 26 9
et? 21 3:: 24
19 19 19 23 15
2cz 15 22 20 IG
13 20
10 23 16 15 18.7
9
Normal
JI DLJOI DENAL
33 33 27 n7
18
HYPE. Hyper. HYPE.
Average
ASD
32 1G 14 24.3
1n 13 18.t;
Comparative studies were made on fourteen patients to determine the relative rapidity of absorption following oral, intraduodenal, and rectal administration in each case. The three tests were made on each patient at intervals of several days, every effort being made to achieve uniformity in technique and in experimental conditions. The results of these studies are tabulated in Table II. The rates of absorption from the rectum in this series varied from 9 to 28 minutes. The average rate for this route of administration for the fourteen cases was 18.7 minutes, a figure which was practically identical with the intraduodenal rate of 18.6 for the same series of cases. The oral rate in this study, however, was several minutes slower, averaging 24.3 minutes for the same series.
248
THE
JOURNAL
OF
ALLERUY
The relation of gastric acidity to absorption from the rectum was also studied in this selected series of cases (Table III). It was found that the absorption was slowest in cases with gastric hyperacidity. In the latter group, the average was 24.2 minutes, as compared to 16.1 and 17.0 minutes for the normal and hypoacidity groups, respectively, iu the same series of Cases. TABIZ RELATION
III
OF GASTRIC ACIDITY TO ABSORPTION RATES FOLLOWING ORAL, DUODENAL, AND RECTAL ADMINISTRATIONS OF PEANUT PROTEIN IN FOURTEE~T CASES
DEGREE OF GASTRIC ACIDITY
Hypoacidity Normal Hyperacidity
NUMBER OF CASES
AVERAGE
ABSORPTION
TIME
DUODENAL
ORAL
-
IN
MINUTES RECTAL
4
17.5
(i
24.5
17.0 16.1
4
31.0
24.2
The normal acidity group average of 16.1 minutes appeared to be more rapid than 6he hypoacidity reading (17 minutes) for the first time in any of our studies. This probably was the result of the small number of cases in this group and of the unusual low reading of 9 minutes in Case 76 (nonspecific ulcerative colitis)! a patient in whom the presence of active ulceration in the lower bowel accelerated absorption to an unusual degree (Table II). The effect of bowel ulceration upon rapidity of absorption had also been noted in the previous study with egg.3 In a case of ulcerative colit,is (listed as Case 7 of Table III in that study), an absorption rate of 7 minutes was obtained following rectal administration of the egg antigen. In three other cases without ulcerative lesions, in the same series, the absorpt,ion rates were 26, 65, and 125 minutes, respectively. The ulcerative case was again tested at a later date when the ulcerative process was healing. At this time a rectal absorption time of 26 minutes was obtained. Of interest is the relation of the absorption rate from the rectum to gastric acidity. It had been noted in previous studies17 2 t,hat, following oral and duodenal administration of the peanut antigen, the absorption rate was definitely retarded in cases with gastric hyperacidity. The same finding had been noted in the rectal studies with the egg antigen.3 In the present studies, with the rectal administration of the peanut antigen, the same principle was found to hold true. In view of these findings, studies were made on about forty subjects to determine whether or not there was any relationship between gastric acidity and rectal pH. The patients studied were all on normal diets. Only the pH of the rectal was’hings, and not. that of the feces, was studied. The rectum was washed with warm tap water, and t.he pH was immediately determined by means of the Heilige-Klett calorimeter. In ten of the patients, two or more studies of the rectal
GRAY
AND
WALZZER:
ABSORPTION
OF
UNDIGESTED
PROTEIN
249
pH were done on successive days to determine whether or not there was any daily variation in the readings. The results obtained in each patient did not vary materially from day to day. The pH readings in this series ranged from 6.4 to 7.4. There were no striking differences in the rectal pH readings of patients with varying degrees of gastric acidity. There was no evidence of an increased acidity in the rectum in cases with gastric hyperacidity, which would account for the slower absorption of antigen in these cases. DISCUSSION
Sussman, Davidson, a,nd Walzer reported that the absorption of egg protein from the rectum was slower than that following its oral administration. This impression was gained in studies on only a few cases in which no standard technique was employed. In the present study with peanut. antigen, carried out under more uniform experiOne mental conditions, this earlier impression could not be confirmed. may conclude from the comparative studies on fourteen selected eases (Table II) that the average rectal and duodenal absorption rates with the peanut antigen closely approximate each other. Absorption following oral administration of the antigen was slower by about 5.6 minutes than the rectal and duodenal rates. In attempting to explain this difference several factors must be kept in mind. Mechanical factors, such as peristaltic activity, tonus and spasm of the pylorus, configuration of t,he stomach, etc., must be considered. The degree of gastric acidity also plays a part. Moreover, the possibility that absorption may take place from the esophagus and stomach must also be taken into account. Absorption from the isolated esophagus and stomach has already been demonstrated experimentally in the MaBcacus rhesus monkey.6 The relative importance of the above-enumerated factors in influencing the rapidity of absorption of orally administered antigen will form the subject of a future communication. The fact. that the average rectal absorption rate in the series of fourteen selected cases differed little from the duodenal rate is also significant. This finding adds considerable support to the position that the absorbed antigen enters the circulation in an undigested form, for there are no active digestive enzymes in the rectum. Further confirmation is obtained in other studies ma,de with similar techniques in human beings and in monkeys which have demonstrated that the absorpbion of antigen occurs from the vagina and uterine cervix,7 from the intact skin,* from the peritoneal, pericardial, and pleural cavities, and from the spinal canal.g The technique employed in the above studies is sensitive enough to detect the absorption of as little as 0.0001 mg. of protein nitrogen into
250
TNK
JOURNAL
OF
ALLERGY
the circulation. The smallness of the amount absorbed does not diminish its importance in the eyes of the allergist, however, for it is sufficient to institute a severe constitutional allergic reaction in the sensitive patient, and in a highly seusitive patient, it is enough to cause death. CONCI,USIONS
The absorption of unaltered peanut antigen, which was previously shown to occur following oral and intraduodenal administration, is now demonstrated following rectal administration. The average absorption rate followin, 0~rectal administ~ration of the peanut antigen approximates that following its intraduodenal introduction and is more rapid than that following its oral inpestion. In patients with gastric hyperacidity, absorption of peanut antigen from the rectum is slightly retarded, a finding which was also noted following the oral and intraduodenal administration of the antigen in these cases. REFEsRE’NC’ES
Studies in Absorption of Undigested Proteins in I., and TValzer, hl. : Human Beings. VI. The Absorption of Unaltered Protein From the Abnormal Gastro-Intestinal Tract, Am. J. Digest. Dis. & Nutrition 3: 403, 1936. Studies in Absorption of IJndigested Proteins in Gray, I., and Walzer, M.: Human Beings. VII. The Absorption of Unaltered Protein Introduced by Duodenal Tube Into the Abnormal Gastro-Intestinal Tract, Am. J. Digest. Dis. 5: 345, 1938 ; J. AT,I,~RGY 8: 31, 1936 (Abstract). Sussman, H., Davidson, A., and Walzer, M.: Absorption of Undigested Proteins in Human Beings. III. The Absorption of Unaltered Egg Protein in Adults, Arch. Int. Med. 42: 409, 1928. Walzer, M.: Studies in Absorption of Undigested Proteins in Human Beings. I. A Simple Direct Method of Studying the rZbsorption of Undigested Protein. .T. Immunol. 14: 144. 1927. Smyth, F. ‘S., and Rtallings, &I.: Studies in Passive Transfer. IV. Rectal Absorption of the Antigen. .J. ALLERGY 3: 16, 1932. Harten, M., Gray, I., Li&gston, S., and Walzer, M.: Absorption of Un digested Protein From the Normal Stomach, Esophagus and Gall Bladder in the Rhesus Monkey, J. ALLERGY 10: 478, 1939. Rosenzweig, M., and Walzer, M.: The Absorption of Antigen From the Vagina and Cervix in Humans, J. ALLERGY 9: X9.5, 1938. IValzer, A.: The Sbsorption of Protein Through the Skin, J. AI.LERGP 10: BP, 1938. To be published.
1. cfmg,
2.
D. 4. 5. 6. 7. 8. 9.
IN ABSORPTION
OF UNDIGESTED
HUMAN VTIT.
ABSORPTION
FROM
THE
OF ABSORPTION
GRAY,
M.D.,
IN
BEINGS
RHCTUM
AND
A
COMPARATIVE
ORAL, DUODENAL,, ADMINISTRATIONS
FOLLOWING
RECTAL IRVING
PROTEIN
AND
MATTHEW
WALZER,
STUDY
AND
M.D.
N. Y.
BROOKLYN,
N PREVIOUS communications the results of studies on the absorption of undigested peanut protein following oral1 and intraduodena12 administrations were reported. It was found that, following intraduodenal feeding, absorption of the peanut antigen was more rapid by several minutes than that following its oral consumption. It was also observed that, in the pres’ence of gastric hyperacidity, the absorption of the antigen was retarded, while in hypoacidity it was accelerated. This obtained, not only following the oral intake of ant,igen, but even when it was administered directly into the duodenum. The present communication deals with the absorption of peanut antigen following its introduction into the rectum. Sussman, Davidson, and Walzer3 had at an earlier date studied the absorption of egg protein from the rectum in a small series of adults. They demonstrated that the direct technique for demonstrating the absorption of unaltered protein which had been employed with oral administration* could be satisfactorily applied in rectal studies. Smyth and Stallings5 at a later date successfully used this technique in a similar study on infants and children. The technique employed in the present study has been described in detail in previous, communications and will be briefly summarized here. The subject to be studied was kept, for forty-eight hours on a diet from which all nuts were carefully excluded. He was then passively locally sensitized to peanut by an intracutaneous injection of human serum obtained from a8patient whose serum showed a, high reagin titer for this antigen. Clinically this patient was extremely sensitive to peanut and showed a very marked cutaneous reaction to a skin test with it. One-twentieth cubic centimeter of a 1 :lO dilution of this serum was injected intracutaneously in the forearm. On the following morning, without any special preliminary preparation of the subject, the peanut meal, consisting of 10 Cm. of raw ground peanuts in 20 cc. of water, was introduced by tube into the rectum. The sensitized cutaneous site was then kept under observation. The onset of a
I
From
Read Brooklyn,
the
Allergy
at the Nov.
Division
semiannual 5. 1936.
of
meeting
the
Jewish
Hospital
of the
Allergy
24b
Of Brooklyn.
Division
of the
Jewish
Hospital
of
246
THE
JOURNAL
OF
ALLERGY
reaction at this site, characterized by erythema, pruritus, formation, heralded the entrance of the peanut into the The interval between the int,roduction of the meal and the of the erythema at the sensitized site was considered the time for that person. TABLE ,Srhrxmv
OF STVDIES
or RECTAL (THIRTY-ONE
(‘ASE NO. 1oti I IO 113 114 123
AGE
SEX
38
M F M *Al
128 129 lU2 103 104
34 ?I 53 38 27 43 27 29 61 37 3“0 53 40 49 30 31 48 37 56 39
IO’S
53
F
109 Ill 1 I6 118
62 30 56 23 55
A9 F AI F
54 46 56 30
F M F F
101 105 107
112 115 II7 II9 121 12"
1 ?(i 127
I"0
124 125 130 131
_-
F A4
M E F M F M M
M M
F A4 F F
F
F
-
DIAGNOSIS Cholelithiasis Cholecystitis Colitis (mucous) Gastric neurosis Chronic cholecystitis IDuodenal ulcer Gastric ulcer Colitis Duodenal ulcer Gastric neurosis Duodenal ulcer Chronic eholecystitis Duodenal ulcer Gastric neurosis Gastric ulcer Gastric neurosis Gastric ulcer Duodenal ulcer Chronic cholecystitis Cholelithiasis Postoperative gall b der disease Ca,rcinomatous ulcer stomach Visceroptosis Cholelithiasis Colitis Visceroptosis Postoperative gall b der disease Chronic cholelithiasis Gastric neurosis Chronic cholec~ystitis Colitis
and wheal circulation. appearance absorption
I ABSORPTION
OF PEANUT
ANTIGEN
Casts)
-___DEGREE OF GASTRIC ACIDITY Normal Normal Normal Normal Normal
Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. Hyper. ____HYPE. HYPE. Hypo.
iBSORPTION TIME IN MINUTES
32 I5 17 I6 I3 14 I4 26 18 36 16 I8 I5 17 23 2 28 13 10 20
Hypo.
22
HYPE. HYPE. Hypo. HYPE. Hype.
21 23 18 13 I9
Hypo. HYPE. HYPE. Hypo. zrage for
E
GROUP hvERAGE IN hlINUTES
11 18 I6 I5 ire Series
18.6
--
21.4
16.8 19.0
The subjects, employed in this study were adults of both Sexes, varying in age from 21 to 62 years, who suffered with various organic and functional disturbances8 of the gastrointestinal tract. The final diagIIosis iIz each case, determined after careful investigation, is listed in Table I. As in previous studies, the cases were roughly divided into three groups according to the degree of gastric acidity. They were designated as cases with hyperacidity, normal acidity, or hypoacidity, according to the commonly accepted standards which were outlined in detail in previous commnnications.l2 Atopic patients mere excluded from the study.
GRAY
AND
WALTZER,:
ABSQRPTION
OF
UNDIGEmSTXD
247
PROTEIN
Following rectal administration of the peanut meal, the absorption rates for the thirty-one cases in this series varied from 10 to 36 minutes. The average for the entire group was 19 minutes. The results of the earlier studies” on egg absorption from the rectum had suggested that the rectal absorption rate might be influenced by the degree of gastric acidity. This impression was confirmed in the present study. It mill be noted from the data presented in Table I that, in the five cases with normal acidity, the average absorption rate was 18.6 minutes. In the thirteen cases with hyperacidity, the average rate was 21.4 minutes, which was somewhat slower than the normal. For the thirteen cases with hypoacidity, the average absorption rate was 16.8, which was more rapid than the normal. TABLE CO~PARATIBE
STVDY OF ABSORPTION RATES ,IDnlINISTRATIONS OP PEAiYl;T
__~ CASE NO.
AGE 34
SEX
--
F
71 72 74 75 iA
47 39 27 RG
M M E M
77 78 79 80 81
“9 56 28 18 62
M F F F M
82 83 84 85
28 31 5G 26
F
-
E9 M F
II
AFTER
THE
PKOTEIPi
DIAGNOSIS
Chronic cholelithiasis Pyloric ulcer Duodenal ulcer Colitis Ulcerative colitis ant1 chronic proctosigmoiditis Duodenal ulcer Arteriosclerosis Chronic cholecystitis Migraine Carcinoma of colon (sigmoid 1 Chronic cholecystitis Duodenal ulcer Chronic gastritis /Gastric neurosis
ORAL, I)UODENAL, IN F'OI-RTEEx CASES
RMTAT,
AHSORPTION TIME INUTES
DEGREE OF GASTRIC ACIDITY
ORAL --. 18
Normal Hyper. Hyper. HYPE. Normal
Hyper. Normal Normal Normal HYPE.
-1
,S
-
I LECTAI, ~-
1f.i
16
23 25 22 20
23 28 26 9
et? 21 3:: 24
19 19 19 23 15
2cz 15 22 20 IG
13 20
10 23 16 15 18.7
9
Normal
JI DLJOI DENAL
33 33 27 n7
18
HYPE. Hyper. HYPE.
Average
ASD
32 1G 14 24.3
1n 13 18.t;
Comparative studies were made on fourteen patients to determine the relative rapidity of absorption following oral, intraduodenal, and rectal administration in each case. The three tests were made on each patient at intervals of several days, every effort being made to achieve uniformity in technique and in experimental conditions. The results of these studies are tabulated in Table II. The rates of absorption from the rectum in this series varied from 9 to 28 minutes. The average rate for this route of administration for the fourteen cases was 18.7 minutes, a figure which was practically identical with the intraduodenal rate of 18.6 for the same series of cases. The oral rate in this study, however, was several minutes slower, averaging 24.3 minutes for the same series.
248
THE
JOURNAL
OF
ALLERUY
The relation of gastric acidity to absorption from the rectum was also studied in this selected series of cases (Table III). It was found that the absorption was slowest in cases with gastric hyperacidity. In the latter group, the average was 24.2 minutes, as compared to 16.1 and 17.0 minutes for the normal and hypoacidity groups, respectively, iu the same series of Cases. TABIZ RELATION
III
OF GASTRIC ACIDITY TO ABSORPTION RATES FOLLOWING ORAL, DUODENAL, AND RECTAL ADMINISTRATIONS OF PEANUT PROTEIN IN FOURTEE~T CASES
DEGREE OF GASTRIC ACIDITY
Hypoacidity Normal Hyperacidity
NUMBER OF CASES
AVERAGE
ABSORPTION
TIME
DUODENAL
ORAL
-
IN
MINUTES RECTAL
4
17.5
(i
24.5
17.0 16.1
4
31.0
24.2
The normal acidity group average of 16.1 minutes appeared to be more rapid than 6he hypoacidity reading (17 minutes) for the first time in any of our studies. This probably was the result of the small number of cases in this group and of the unusual low reading of 9 minutes in Case 76 (nonspecific ulcerative colitis)! a patient in whom the presence of active ulceration in the lower bowel accelerated absorption to an unusual degree (Table II). The effect of bowel ulceration upon rapidity of absorption had also been noted in the previous study with egg.3 In a case of ulcerative colit,is (listed as Case 7 of Table III in that study), an absorption rate of 7 minutes was obtained following rectal administration of the egg antigen. In three other cases without ulcerative lesions, in the same series, the absorpt,ion rates were 26, 65, and 125 minutes, respectively. The ulcerative case was again tested at a later date when the ulcerative process was healing. At this time a rectal absorption time of 26 minutes was obtained. Of interest is the relation of the absorption rate from the rectum to gastric acidity. It had been noted in previous studies17 2 t,hat, following oral and duodenal administration of the peanut antigen, the absorption rate was definitely retarded in cases with gastric hyperacidity. The same finding had been noted in the rectal studies with the egg antigen.3 In the present studies, with the rectal administration of the peanut antigen, the same principle was found to hold true. In view of these findings, studies were made on about forty subjects to determine whether or not there was any relationship between gastric acidity and rectal pH. The patients studied were all on normal diets. Only the pH of the rectal was’hings, and not. that of the feces, was studied. The rectum was washed with warm tap water, and t.he pH was immediately determined by means of the Heilige-Klett calorimeter. In ten of the patients, two or more studies of the rectal
GRAY
AND
WALZZER:
ABSORPTION
OF
UNDIGESTED
PROTEIN
249
pH were done on successive days to determine whether or not there was any daily variation in the readings. The results obtained in each patient did not vary materially from day to day. The pH readings in this series ranged from 6.4 to 7.4. There were no striking differences in the rectal pH readings of patients with varying degrees of gastric acidity. There was no evidence of an increased acidity in the rectum in cases with gastric hyperacidity, which would account for the slower absorption of antigen in these cases. DISCUSSION
Sussman, Davidson, a,nd Walzer reported that the absorption of egg protein from the rectum was slower than that following its oral administration. This impression was gained in studies on only a few cases in which no standard technique was employed. In the present study with peanut. antigen, carried out under more uniform experiOne mental conditions, this earlier impression could not be confirmed. may conclude from the comparative studies on fourteen selected eases (Table II) that the average rectal and duodenal absorption rates with the peanut antigen closely approximate each other. Absorption following oral administration of the antigen was slower by about 5.6 minutes than the rectal and duodenal rates. In attempting to explain this difference several factors must be kept in mind. Mechanical factors, such as peristaltic activity, tonus and spasm of the pylorus, configuration of t,he stomach, etc., must be considered. The degree of gastric acidity also plays a part. Moreover, the possibility that absorption may take place from the esophagus and stomach must also be taken into account. Absorption from the isolated esophagus and stomach has already been demonstrated experimentally in the MaBcacus rhesus monkey.6 The relative importance of the above-enumerated factors in influencing the rapidity of absorption of orally administered antigen will form the subject of a future communication. The fact. that the average rectal absorption rate in the series of fourteen selected cases differed little from the duodenal rate is also significant. This finding adds considerable support to the position that the absorbed antigen enters the circulation in an undigested form, for there are no active digestive enzymes in the rectum. Further confirmation is obtained in other studies ma,de with similar techniques in human beings and in monkeys which have demonstrated that the absorpbion of antigen occurs from the vagina and uterine cervix,7 from the intact skin,* from the peritoneal, pericardial, and pleural cavities, and from the spinal canal.g The technique employed in the above studies is sensitive enough to detect the absorption of as little as 0.0001 mg. of protein nitrogen into
250
TNK
JOURNAL
OF
ALLERGY
the circulation. The smallness of the amount absorbed does not diminish its importance in the eyes of the allergist, however, for it is sufficient to institute a severe constitutional allergic reaction in the sensitive patient, and in a highly seusitive patient, it is enough to cause death. CONCI,USIONS
The absorption of unaltered peanut antigen, which was previously shown to occur following oral and intraduodenal administration, is now demonstrated following rectal administration. The average absorption rate followin, 0~rectal administ~ration of the peanut antigen approximates that following its intraduodenal introduction and is more rapid than that following its oral inpestion. In patients with gastric hyperacidity, absorption of peanut antigen from the rectum is slightly retarded, a finding which was also noted following the oral and intraduodenal administration of the antigen in these cases. REFEsRE’NC’ES
Studies in Absorption of Undigested Proteins in I., and TValzer, hl. : Human Beings. VI. The Absorption of Unaltered Protein From the Abnormal Gastro-Intestinal Tract, Am. J. Digest. Dis. & Nutrition 3: 403, 1936. Studies in Absorption of IJndigested Proteins in Gray, I., and Walzer, M.: Human Beings. VII. The Absorption of Unaltered Protein Introduced by Duodenal Tube Into the Abnormal Gastro-Intestinal Tract, Am. J. Digest. Dis. 5: 345, 1938 ; J. AT,I,~RGY 8: 31, 1936 (Abstract). Sussman, H., Davidson, A., and Walzer, M.: Absorption of Undigested Proteins in Human Beings. III. The Absorption of Unaltered Egg Protein in Adults, Arch. Int. Med. 42: 409, 1928. Walzer, M.: Studies in Absorption of Undigested Proteins in Human Beings. I. A Simple Direct Method of Studying the rZbsorption of Undigested Protein. .T. Immunol. 14: 144. 1927. Smyth, F. ‘S., and Rtallings, &I.: Studies in Passive Transfer. IV. Rectal Absorption of the Antigen. .J. ALLERGY 3: 16, 1932. Harten, M., Gray, I., Li&gston, S., and Walzer, M.: Absorption of Un digested Protein From the Normal Stomach, Esophagus and Gall Bladder in the Rhesus Monkey, J. ALLERGY 10: 478, 1939. Rosenzweig, M., and Walzer, M.: The Absorption of Antigen From the Vagina and Cervix in Humans, J. ALLERGY 9: X9.5, 1938. IValzer, A.: The Sbsorption of Protein Through the Skin, J. AI.LERGP 10: BP, 1938. To be published.
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