BLOOD SURFACE TENSION, SEDIMENTATION RATE, AND HYPERTENSIVE BLOOD PRESSURE RESPONSES FOLLOWING THE INGESTION OF ALLERGENIC FOODS* CLEMENT
J. SULLNAN,
M.D., AND WARREN RICHMOND,
T. VAUGHAN,
M.D.
VA.
T
HE purpose of this study was to devise a simple clinical test for the detection of the presence of food allergy, and to study the effect that ingestion of allergenic foods may have on the blood surface tension, sedimentation rate, and blood pressure. This work was done on allergic and nonallergic individuals, the total number of cases being eighty-five. Not all of the allergic patients were known or proved to be sensitive to the test food. These tests were carried out simultaneously with other procedures used for the detection of the presence of specific food allergy. Cases which exhibited a positive leucopenic index test to the test food were classified as positive. The cases in which there was a specific positive history, a positive skin test, and a marked degree of leucopenia during the test were classified as strongly positive. In a number of cases in this group there was a definite aggravation of the patient’s disorder following ingestion of the test food. All cases which did not fall into the above two groups were classified as negative. The value of the leucopenic index as a diagnostic aid in the detection of the presence of food allergy has been reported by Vaughan,lT 2 Rinkel and Gay,3 Zeller,4 Dean and others5 and by Squier.6 SURFACE TENSION
Du Nouy’-I” found transient changes in serum surface tension following the production of antibodies after smallpox vaccination. These changes were characterized by a rise in the surface tension values, measured immediately after pouring the specimen, and an increase in the two-hour time drop of the surface tension values, determined by remeasuring the surface tension two hours after pouring the sample. Zunz, McKinley, LaBarre, and Homes14-20 reported that the initial surface tension values were low during or following anaphylactic shock. Wilhelmj and Fleisher, 21, 22 Nicholls and Harrop,2s Leiter,24 C1ausen,25 Haden and Orr,26 Benhamou and Beguet,27* 28 Yogle,2e Natton-Larrier and Grimard-Richard,30 Clerc, Paris, and Sterne,31 Archard, Levy, and Georgiahakis, 32 Kopaczewski,33 Lumiere and Meyer,34-36 Ogawa,“? and ‘From the Vaughan-Grahanr Clinic, Richmond, Va. Read before the TwelPth Annual Meeting of the Society for the Study of Asthma and Allied Conditions, Atlantic City, N. J., May 1, 193’7. 48
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NicholkP measured the surface tension of the blood in a wide variety of clinical and experimentally induced conditions. In the majority of infectious and metabolic disorders studied, abnormal surface tension values were detected. Following digestion and absorption there should be an increase in the blood content of substances which lower the surface tension. Benhamou and Beguet3s and Cosmovici4” were able to demonstrate a fall in blood surface tension during the course of digestion. We have measured the surface tension before and following ingestion of allergenic foods in an att,empt to determine whether, in such conditions, there are any characteristic abnormal changes. In measuring surface tension we have adhered to the technique employed by
POSITIYE S~RONSLY
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Du Nou~.‘-~* I2 Samples of titrated blood, diluted 20 times in physiologic saline, were used. Zunz 1512a has shown that the addition of sodium citrate to plasma does not alter the surface tension of the plasma. Du NouylO was able to demonstrate the persistence of changes in the surface tension of serum after it had been diluted in physiologic saline as much as 10,000 times. On the basis of other information mentioned above, each case from an allergic standpoint was classified as negative, positive, or strongly positive. In the negative group the food ingested was nonallergenic; and in the strongly positive group the food was almost certainly allergenic. For each of these groups the average surface tension readings were computed. The average figures in the three groups were analyzed
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and compared in an effort to determine whether any characteristic differences in surface tension existed between the negative, positive, and strongly positive cases. These differences in surface tension are shown in Table I. It is seen that there is a wider fluctuation in the surface tension values after eating than during the fasting state. In the strongly positive group, after the ingestion of an allergenic food, the surface tension falls to a lower level than it does in the negative group after ingestion of nonallergenic foods. The two hour time drop was found to be of the same degree in the allergic and nonallergic groups. In two series of cases the technique was varied slightly. Instead of using different pipettes for the collection and dilution of the blood samples, the same pipette was used to collect all six samples in each individual case. In one series the surface tension readings were taken immediately after pouring the sample. In the ot,her series the readings were taken two hours after pouring. In these two series the findings were almost identical with those obtained in the first series of cases illustrated in the table. Although we have found an abnormally low fall in surface tension of the blood following ingestion of an allergenic food, the degree of abnormality is small. Because of the slight degree of difference between the normal and abnormal, it would not be practicable to employ measurement of the blood surface tension, by the method employed by us, as a clinical test for the presence of specific food allergy. Our findings would indicate that the surface tension changes previously reported as a finding in anaphylactic shock are probably conditioned more by the state of shock than by any specific allergic response. No surface tension changes of pronounced degree occur in the specific allergic responses seen clinically, although it seems probable that the phenomenon might be observed in human anaphylactic shock. SEDIMENTATION
RATE
It ia possible that the difference between the blood of allergic and nonallergic individuals may be such that the suspension stability of the erythrocytes is altered in the allergic state. Ellis41 has reported that the sedimentation rate of allergic individuals is slower than that Schulhof42 and Uffe43 have found that a of nonallergic individuals. small percentage of allergic individuals have an abnormally slow sedimentation rate. Westcott and Spain44 concluded from their studies that the sedimentation of the erythrocytes, in the allergic state, does not proceed at an abnormally slow rate of speed. Again, during the actual allergic attack, the constituents of the blood are probably altered and not the same as before the attack. It is conceivable that here again such alterations might possibly manifest themselves by a changed rate of erythrocyte sedimentation. However, Gel-
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fand and Victor45 were unable to demonstrate any marked changes in the sedimentation rate of cases of pollinosis before and during the season of pollination. In our work we have divided our cases into groups. The same criteria that have been mentioned above were employed to determine whether the ingested food was allergenic or nonallergenic. On the basis of this information our cases were classified as negative, positive, or strongly positive, and each group subdivided into male and female. Average curves were computed for each group of the sedimentation rate, fasting, one hour after eating, and two hours after eating. A comparison of the three curves in each group showed no change in the sedimentation rate following the ingestion of food, whether the food was allergenic or nonallergenic. The fasting rate of sedimentation was abnormally slow in only two patients of our allergic group. In the other eases the average rate of sedimentation was no slower than in the nonallergic individuals. BLOOD
PRESSURE
Numerous investigators have observed that the blood pressure of allergic individuals is very often lower than that of nonallergic individuals. The literature contains very few report,s of hypertension causatively related to allergy. Waldbott46 reported several cases of familial hypertension in allergic individuals. In these cases avoidance of allergenic foods was accompanied by reduction of the blood pressure. L. P. Gay in an exhibit before the Southern Medical Association (1935) presented a series of allergic patients with hypertension in whom the blood pressure fell following dietary avoidance of allergenic foods. Reingestion of certain foods was associated with a pressor response. In our 85 cases blood pressure determinations were made with the Tycos recording sphygmotonograph. Two readings were taken on the fasting patient; four other readings were taken at half-hour intervals following the ingestion of the test food. In only two cases were there any marked changes in the blood pressure. In none of the cases did the diastolic blood pressure vary by more than 15 mm. of mercury, and in about 90 per cent of the cases this variation, up or down, was no more than 10 mm. of mercury. In all but two cases the systolic blood pressure did not rise or fall more than 12 mm. In one of these two cases the blood pressure rose 20 mm. at the end of thirty minutes and 30 mm. at the end of two hours after ingesting the offending food. In the other case there was a blood pressure rise of 17 mm. of mercury one hour after eating and 2’7 mm. two hours after eating.
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In both of these cases the skin reactions were strongly positive and there was clinical improvement associated with avoidance of these foods. In one case there was an accompanying leucopenia of 2,275 cells, and in the other case a definite aggravation of the clinical condition following the ingestion of this test food. In these two cases there can be very little doubt that these particular foods were allergenic. However, there was no marked elevation of the blood pressure in any of the other patients who had ingested allergenic foods. These observations, together with others which are to be reported elsewhere,47 suggest that in individuals with a primary hypertensive tendency, food allergy might serve as an exciting factor provided the circulatory regulatory mechanism happens to be a shock tissue. CONCLUSIONS
1. Following the ingestion of allergenic foods the surface tension of diluted titrated blood falls to an abnormally low level. However, the difference between the normal and the abnormal is of such small magnitude that the test cannot be used as a clinical method for the diagnosis of specific food allergy. 2. There are no pronounced changes in the sedimentation rate of the blood corpuscles following ingestion of allergenic foods. 3. In some allergic individuals, the ingestion of a food to which there is an existing hypersensitiveness, is followed by a slightly abnormal increase in the systolic blood pressure. REFERENCES
1. Vaughan, Warren T.: Food Idiosyncrasy as a Factor in the Digestive Leucoeyte Responce, J. ALLERGY 6: 421, 1935. 2. Idem: The Leucopenic Index as a Diagnostic Method in the Study of Food Allergy, J. Lab. & Clin. Med. 21: 7278, 1936. 3. Rinkel, H., and Gay, L.: The Leukopenic Index, J. Missouri M. A. 33: 182, 19.76. 4. Zeller, M.: The Leucopenic Index in Intractable Asthma, Illinois M, J. 69: 54, 1936. 5. Dean, L., and others: The Treatment of Allergic Rhinitis, J. A. M. A. 108: 251, 1937. 6. Squier, T.: The Hematologic Response in Food Allergy Eosinophilia in the Leueopenic Index, J. ALLERGY 8: 250. 1937. IX. Time Drop and Smallpox Vaccine, J. 7. du Nouy, P. L.: Surface Tension. Exper. Med. 40: 129, 1924. 8. Idem: Spontaneous Decrease of the Surface Tension of Serum, Ibid. 35: 575, 1922. 9. Idem: Surface Tension of Serum. II. Action of Time on the Surface Tension of Serum Solutions? Ibid. 35: 707, 1922. Surface Tension of Serum. V. Relation Between Time Drop and Serum 10. Idem: Antibodies. Ibid. 37: 659. 1923. 11. Idem: Surface Tension of’ Serum. VI. Study of Immune Serum. Time Drop and Initial Value of Surface Tension, Ibid. 38: 87,, 1923. 12. Idem: Surface Tension of Serum. XIII, On Certain Physic0 Chemical Changes in Serum as a Result of Immunization, Ibid. 41: 779, 1925. 13. du Nouy, P. L., and Baker, L. E. Surface Tension of Serum. XIV. Concerning the Chance in Surface Tension as a Result of Immunization. Ibid. 42: 9, 1925. 14. McKinley, E. B., and Zunz, E.: De la tension superflcielle du plasma apres 1:iniection au cobave des globulines du serum normal de eobave,“_ Compt._ rend. Sot.” de biol. 93: 459, 1925:
SULLIVAN 15. Zunz, 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28.
29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47.
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E.: De la Tension Superficielle du Plasma de Choc Spontanement, Ibid. p. 463. La Barre. J.: Sur les modifications du ulasma lors du ehoc histaminiaue et ses rapports avec l’abaissement de la tension superficielle, Compt. rend. Sot. de biol. 95: 237, 1926. Zunz, E., and La Barre, J.: Tension superficielle et coagulation du plasma lors du choc histaminique du chien, Ibid. p. 722. Idem: Modifications de la coagulabilite et de la tension superficielle du plasma lors de l’anaphylaxie serique chez des cobayes decerebres, Ibid. p. 858. Homes, G., and Zunz, E.: La tension superficielle statique de plasma dans le choc anaphylactique serique, Ibid. 97: 1173, 1927. Zunz, E.: De la tension superficielle du plasma de choc peptonique, Ibid. 94: 776, 1926. Wilhelmj, C., and Fleisher, M.: Relation of the Thyroid Gland to the Surface Tension of the Blood Plasma. I. The Effect of Thyroidectomy, J. Exper. Med. 43: 179, 1926. Idem : The Relation of the Thvroid Gland to the Surface Tension of the Blood II. Effect of Administration of Thyroid Extract and Thyroxiu, Plasma. Ibid. p. 195. The Surface Tension of the Blood Serum in Nicholls, E., and Harrop, G.: Hyperthyroidism, J. Clin. Investigation 5: 181, 1928. The Surface Tension of the Blood Serum in Nephritis, J. Clin. Leiter, L. : Investigation 3: 267, 1926. III. The Surface Tension of the Clausen, 5. : Parenchymatous Nephritis. Blood Serum, Am. J. Dis. Child. 29: 594, 1925. Surface Tension of the Blood Serum of the Dog After Haden, R., and Orr, T.: Upper Gastrointestinal Tract Obstruction, J. Exper. Med. 44: 425, 1926. La tension superficielle du serum dans quelques Benhamou, E., and Beguet, M.: etats de choc chez l’homme, Compt. rend. Sot. de biol. 107: 1542, 1931. Idem : La tension superfieielle du serum chez l’homme normal et dans quelques etats pathologiques, Ibid. 110: 54, 1932. Yogle, E.: Surface Tension of Blood Serum in Syphilis, J. Immunol. 16: 17, 1929. Natton-Larrier. L.. and Grimarcl-Richard. L. : Permeabilite ulacentaire et tension superfieielle ‘du ‘serum, Compt. rend. Sot. de biol. 113: 257, 1933. Clerc, A., Paris, R., and Sterne, J.: De l’action hypotensive arterielles de certaines substances qui abaissent la tension superficielle, Ibid. p. 360. Archard, Ch.. Levy, J.. and Georgiahakis, N.: Tensions superficielles des serums icteriques,’ Ibid: ‘p. 805. Kopaczewski, W. : Tension superficielle sanguine et protection contre les etats de choc, Ibid. 116: 1334, 1937. Lumiere. A.. and Mever. P.: Recherches sur l’etat colloidal du serum traite par ljamihon, Arch.“internat. de pharmacodyn. et de therap. 50: 339, 1935. du kaolin sur le serum traite par l’amiclon et sur le serum Idem : 1’Action frais de cobaye, Ibid. 51: 105, 1935. Idem : Recherches sur l’etat colloidal du serum traite par l’amidon. II. Ibid. p. 133. Ogawa, J.: Endocrine Glands and Surface Tension of Blood Serum, Jap. J. Obst. & Gynec. 14: 544, 1931. Nicholls? .E.: Surface Tension of Human Blood Under Normal and Pathological Condrtrons, Bull. Johns Hopkins Hosp. 42: 358, 1928. Benhamou, E., and Beguet, M.: La tension superflcielle au eours de la digestion, Compt. rend. Sot. de biol. 110: 56, 1932. Cosmoviei, N.: La tension superficrelle au tours de la digestion, Ibid. 111: 129, 1932. Is There an Increased Suspension Stability of the Erythrocytes in Ellis, R.: Allergic Disease? J. ALLERQY 7: 64, 1935. Schulhof, K.: Increased Suspension Stability of the Erythrocytes. Its Frequency in Allergic Individuals and Their Relatives, J. A. M. A. 100: 318, 1936. Uffe, A.: Blood Sedimentation Rate in Allergic Disease, J. ALLERGY 4: 379, 1933. Westeott, H., and Spain, W. C.: Sedimentation of Red Blood Cells in Allergic Diseases, J. ALLERGY 4: 370, 1933. Gelfand, H., and Victor, G.: The Sedimentation Rate in Hay Fever Before and During the Seasonal Exacerbation, J. ALLERGY 5: 583, 1934. Waldbott, G. L.: Hypertension Associated With Allergy, J. A. M. A. 94: 1390, 1930. Vaughan, W. T., and Sullivan, C. J.: On the Possibility of an Allergic Factor in Essential Hypertension, J. ALLERGY. To be published.