REVIEW OF CARCINOIDS IN CHILDREN

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Functioning Carcinoid in a I 5-year-old Male

Jack Lavyrl Field, M.D., Lucile Frances Adamson, Ph.D., and Harry E. Stoeckle, M.D.

Department of Pediatrics, University of Missouri Medical School, University of Missouri Medical Center

cells not detected in the gastrointestinal tract. There is agreement that gastrointesti nal carcinoids arise from the Kulchitsky's cells of the gastrointestinal tract. However, there are diverse opinions as to the origin of bronchial adenomas. The term â€œ¿ade nomaâ€• is used with different connotations, and still other classifications have been used.@ Bronchial carcinoids reported in chil dren are not included in our review.

Isler and Hedinger,12 in 1953, were first to suggest that metastasizing carcinoid of the small intestine and valvular disease of the heart occur as a definite syndrome. In 1954, Thorson and co@workers13 first com pletely described the combination of an extra-appendicial carcinoid, metastasis to the liver, systemic symptoms, and the pro duction of excess 5-hydroxytryptamine or serotonin. The primary carcinoids in these cases were located in the small intestine with metastasis to the liver and were associ ated with flushing of the skin, an unusual type of changing cyanosis, frequent watery stools, asthma, valvular disease of the right side of the heart, and, terminally, edema and ascites. This complex is now commonly referred to as the â€œ¿malignantcarcinoid syndrome.â€•

Mattingly,'4 in 1956, grouped carcinoids into â€œ¿functioningâ€•and â€œ¿nonfunctioning.â€• Functioning carcinoids include those cases in which there is either elevated content of serotonin in blood or any elevated urinary excretion of a serotonin metabolite, such as 5-hydroxyindoleacetic acid (5-HIAA) (Fig. 1). Other authors note that any single sign or symptom of the syndrome may be the sole or predominant evidence of a function ing carcinoid.1518

O ECONOMOPOULO51 recently reviewed the literature for argentaffin tumors of the appendix in the pediatric age group and added three cases of his own. He found that these tumors presented as acute ap pendicitis, while the definitive diagnosis was established as a coincidental finding from the study of pathologic specimens. Usually, the tumor is found as a small nodule in the distal end of the appendix, but it may occur proximal to the end, oc clude the lumen, and produce obstructive appendicitis.2 Such tumors of the appendix are rare in children, and even more rare have been reports of extra-appendicial ar gentaffin tumors discovered in children.

The term â€œ¿carcinoidâ€•was first suggested by Oberndorfer,' in 1907, for the non metastatic argentaffin tumor. Argentaffin tumors have since been established as po tentially malignant, but are commonly re ferred to as carcinoids. Since 1937, the term â€œ¿carcinoidâ€•has also been used to define a type of bronchial adenoma with similar histologic features.4 Bronchial carcinoids are uncommon in adults and rare in chil dren. Cathala et al.@have recently reported a case of bronchial carcinoid with metas tasis to the hilar lymph nodes in a 10-year old girl, but gave no evidence of liver metas tasis or carcinoid syndrome. In a few adults, bronchial carcinoid with metastatic carcinoid of the liver and no evidence of intestinal carcinoid has been associated with the malignant carcinoid syndrome.6b0 Stan ford et al.6 have suggested that the tumor in the liver could possibly be a primary tu mor. Sjoerdsmahl mentioned the possibility that both pulmonary and liver tumors may be metastatic from a small nest of carcinoid

ADDRESS: (J.L.F.) 807 Stadium Road, Columbia, Missouri.

PErwnucs, June 1962

953

(2)

We have been able to find reports of 19 cases of carcinoid in patients 16 years old and under (Table J).1 2,19-25Fifteen of these were located in the appendix. None of these reports indicated that there was evidence of functioning carcinoid. Raiford mentioned that multiple nodules were present in one 16-year-old female, and, although he stated that the nodules appeared malignant, the presence of multiple nodules may not indi cate metastasis. Other authors have noted

as many as 30 primary nodules.15-22,2628 Of

the four extra-appendicial tumors, one oc curred in a Meckel's diverticulum. Another extra-appendicial tumor was reported in the stomach, and two have been found in the ileum. A 6-year-old male reported by Webster was noted to have large mesenteric nodes, but biopsy specimens were not taken. The 4-year-old male reported by McCartney is the youngest patient re ported, and the carcinoid was a very small

PROTEIN â€˜¿@â€˜¿,â€˜¿.,

nodule found to be the leading point of an intussusception.

Among the original group of patients re ported by Thomson et al.13 were three who had symptoms suggestive of the syndrome

during childhood. One of these, a 19-year

old patient, was first described by BiÃ¶rck

et al.29and noted to have exertional dyspnea

at 6 years. By 11 years of age, he had asthma with cyanosis and exanthema over the face. Another was noted to have inter mittent cyanosis and heart disease at the age of 14, and the third had a history of a bluish-red color to his face since â€œ¿child hood.â€•

Recently we have had the opportunity to

study a 15-year-old boy in whom the diag

nosis of functioning carcinoid was estab lished prior to surgery.

History

CASE REPORT

J. S. (02-69-40),

a 15-year-old

male,was

admitted to the University of Missouri

Medical Center December 1, 1960. He had been perfectly well until the spring of 1960

when he began having episodes of abdomi

nal cramping. Within a few months, he

developed occasional vomiting. Usually the

abdomen became tight and hard, with loud growling that actually could be heard throughout the house and often awakened his parents in another room. Initially, these episodes occurred frequently in the eve nings and night. He developed nocturia of one or two times each night, and for one month had nocturnal enuresis associated

with the cramping episodes. Stools re

mained normal.

One month prior to admission, he began having periodic flushing, especially in the mornings, associated with a feeling of tight ness of the chest and very mild difficulty in breathing, but no audible wheeze. The episodes of flushing and mild dyspnea in creased in frequency' but were not particu

larly associated with abdominal cramping.

There was a short episode of diarrhea just

prior to admission. Dryness and flaking of the skin over the legs had been noted only

-â€˜ -9 - NIACIN

â€˜¿k/'@'â€¢¿9..,@

H OTHER MINOR METABOLITES

TRYPTOPHAN

I

COOH

vy

5-HYDROXY-TRYPTOPHAN

CO@

HO.ff@.â€”@_CH@-â€”CH2â€”â€”NH2

5- HYDROXY-TRYPTAMINE (SEROTONIN)

NH @

HO. (@iâ€”@-â€” CHtâ€”CNO

5- H'rDROXY-INDOLEACETALDEHYDE

1@

HO CH1 C 00$

GLUCURONCE 4â€” > SULFATE

5-HYDROXY-INDOLE ACETIC ACID (5-HIAA)

(3)

AuthorAge

(yr)SexLocaiwnPresenting Dmgno.ns&kHicks

&

Kadinski'912MMeckel'sAppendicitis..diverticulumForbus2Â°12MAppendixAppendicitisRaiford2'16

15

14

15

16

15

12F

F

M

MAppendix

Appendix

AppendixAppendicitis

Appendicitis

AppendicitisMultiple

nodules; â€œ¿appeared

malignantâ€•

..

.. ..Foreman,212FAppendixAppendicitis..Lutzow-HÃ¶Im,@15FStomachGastric

polypNo after9evidence of metastasis yearsWebster236

10 10M

F FIleum

Appendix

AppendixIntussusception Appendicitis AppendicitisLarge,

mesentenic nodes; no

biopsy

..Kevorkian2411FAppendixAppendicitis..McCartney2'4MIleumIntussusceptionOeconomopoulos'12

13 9M

M

FAppendix

Appendix

AppendixAppendicitis

Appendicitis

Appendicitis.. ..

ARTICLES

955

TABLE I

N0NFUNCTIONING CARCINOIDS REPORTED IN PATIENTS 16 YEARS OLD AND UNDER

a short time. He had lost 22 lb (10.0 kg) during a 3-month interval. On the day of admission he had developed severe abdomi nal cramping, marked abdominal disten tion, and very loud rushes of growling and

bubbling in the abdomen.

Physical Findings

The patient was an alert, white male who appeared to have lost considerable weight. His pulse was 84 per minute; blood pres sure, 110/64 mm Hg; respirations, 20 per minute; temperature 100.4Â°F (38.0Â°C) rec tally; weight, 103 lb (46.7 kg); and height, 63 in (160 cm). A mild malar flush was noted. Most remarkable was the distended abdomen with visible peristalsis and ex tremely loud bowl sounds that could be heard from outside the examining room. The lower extremities were cold and pale, with a suggestion of cyanosis. The skin over the lower extremities was dry and rough, with a fine flaking appearance and no hy perpigmentation. Bilateral reducible in

guinal hernias were present. Otherwise, the physical findings were within normal limits (Table II).

Hospital Course

The patient was afebrile throughout his hospital course. He continued to have in

termittent abdominal cramping with visible

peristaltic waves and loud borborygmus, occurring most frequently in the early morning and late evening. Eating seemed to aggravate the episodes. He became pro gressively more anoretic and lost 7.5 lb (3.4 kg) in 20 days.

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Finding Value

On December 27, 1960, a laparotomy dis closed a 2-cm spherical, cream-colored tu mor of the ileum that unilaterally com pressed the intestinal lumen, with striking hypertrophy and dilatation of the intestine proximal to the tumor. Many cream colored nodules were visible in the liver, and the entire liver was nodular to palpation. Ap proximately 4 ft of small intestine were removed, so that normal-sized lumens could be anastomosed. One of the nodules in the liver was excised. Microscopic studies of both areas of tumor tissue revealed ana plastic cells lying in nests within fibrous tissue. The cells were arranged in disori ented clumps and contained only a small

amount of cytoplasm. The nuclei were

small, of fairly uniform size, and stained darkly. There were no mitotic figures. These

findings were consistent with malignant

carcinoid of the ileum, with metastases to

the liver.

COMMENT

The first symptoms of abdominal cramp ing that this patient developed, when he

was 14 years old, could have been due

either to the action of serotonin or partial obstruction by the primary tumor. Sero tonin is a potent smooth muscle stimulant, and the human intestine is very sensitive to its action.'Â° Evidence has been presented that the motility response is mediated through the cholinergic nerves distal to the ganglia.'Â°'@' Abdominal cramps, nausea, and vomiting are the main gastrointestinal ef fects obtained by infusion of the serotonin precursor, 5-hydroxytryptophan.â€• The diar rhea that frequently occurs in patients with functioning carcinoid is believed due to this hypermotility.'4'15'28â€•2 Our patient soon de veloped nocturia and then enuresis. Sero tonin administered to dogs has been shown to produce urination; when administered to man, it may produce a desire to empty the bladder.15

Fluctuations of blood serotonin have been thought to be responsible for the flushing seen with carcinoid, but this has not been proved. Recently Pearl et

@ produced TABLE II LABORATORYFINDINGS Hemoglobin Hematocrit Total leukocytes Neutrophils Lymphocytes Monocytes Total eosinophils ESR (Wintrobe) Routine urinanalysis Stools Occult blood Culture

Ova and parasites

Skin tests

PPD, intermediate strength

Histoplasmosis Brucella Febrile agglutinins Total protein in serum

Albumin Globulin

Sulfobromophthalein

Transaminase, SGOT

Alkaline phosphatase Prothrombin time (after 10

mg. vitamin K each day for 5 days in preparation for surgery) Control Patient Electrocardiogram Phonocardiogram X-ray Chest

Upper GI series

Barium enema

plained of a tightness in his chest. These episodes seemed to be initiated by exertion or anxiety and did not consistently occur with the abdominal complaints. With these findings suggestive of functioning carcinoid, 24-hour urine specimens were obtained for 5-HIAA. Three determinations prior to sur gery ranged from 55.1 to 126.2 mg, sup porting the diagnosis of functioning carci noid (Table III).

13 gm/100 ml 40% 7,150/mm' 57% 36% 7% 139/mm' 5 mm negative

3+, tr., 4+, 4+, tr. No entenic pathogens

(2 cultures)

None seen (8 examina

tions)

negative positive

negative negative 7.1 gm/100 ml 5.1 gm/100 ml 2.0 gm/100 ml

0.4% retention

16 units 8.9 K. A. IJ.

13.5sec.

19.0 sec. normal normal

normal

massive dilatation of je

junum and ileum;

some barium in colon at 2 hours

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Date5-HIAA/5@ hours(mg)1960Dec.15

20

23

27f

29

30

31126.2

69.0

55.1

74.4

47.0

55.61961Jan.1

3

486.9

76.9

115.1Feb.1071.4March1615.7July692.0

ARTICLES

typical flushes in a patient with functioning carcinoid by administering small amounts of epinephrine or norepinephrine intra venously and has demonstrated a simul taneous increase of a compound in the plasma indistinguishable from serotonin. However, repeated single injections or con tinuous infusion or serotonin in the same patient failed to produce typical flushes.

The increasing severity of the symptoms of partial intestinal obstruction was the presenting complaint, and it was a day or two after admission to the hospital before flushing was noted to be significant. It was then discovered, upon auscultation of the chest during these episodes, that there were scattered fine wheezes commonly described as a feature of the carcinoid syndrome. Pulmonary function studies were sugges tive of mild restrictive pulmonary insuffi ciency.

As much as 60% of the tryptophan intake may be utilized in the production of sero tonin by functioning carcinoids.'@ It has been postulated that this may result in in adequate niacin and protein synthesis, and that a pellagra-like picture may result.'5â€•5 However, the major part of the body re quirement of niacin is usually from dietary sources. The frequent episodes of abdomi nal discomfort and progressive intestinal obstruction with anorexia in this patient could have led to dietary deficiencies. He had lost considerable weight, and the skin over the legs was dry, atrophic, and flaking, although there was no hyperpigmentation as seen in pellagra.

A 24-hour urine output of 5-HIAA greater than 25 mg is considered to be diagnostic of malignant carcinoid. Normal range is 2 to 9 mg per day.h1 The qualitative test will be positive on a single specimen when

24-hour urine output is 1,000 ml and ex

cretion is more than 40 mg.36 A qualitative urine test for 5-HIAA was done initially, and findings were positive. Repeated quan titative determinations demonstrated fairly wide fluctuations with one low determina tion of 15.7 mg (Table III).

Hanson and Serin3? reported one case of

TABLE III

QUANTITATIVE TESTS FOR URINE 5@1HAA*

*The 24-hour urine tests for 5-HIAA were done with

theâ€œ¿HycelUrineSerotoninset,â€•distributedby Sci

entific Products, Catalogue number 53865. t Surgery, primary tumor removed.

malignant carcinoid in which the daily ex cretion of 5-HIAA fluctuated over a broad range. One determination was as low as 6 mg. Davis and Rosenburg38 studied a 25-year-old female with carcinoid who had had flushing for 3 years and elevated blood serotonin, but found normal 24-hour

urine 5-HIAA excretion throughout 8

months of frequent testing. Some qualita tive methods also give a few false-positive results. Bananas and a few other foods, as well as some medicaments, may cause ab normally high values.â€•

(6)

Dec. 22,1960*First hour 451.017Second

hour 371.015Third hour 361.016Fourth

hour681.010(Per

cent of loadâ€”21%)March

16, 1961fFirst

hour 1701.002Second

hour 3001.001Third

hour 2401.000Fourth

hour601.002(Per

cent of loadâ€”80%)

0.1 to 0.3 @tg/ml.â€•It has been suggested that free plasma levels may differ,42 but various techniques of determining platelet bound and free serotonin have given vail able results and are not usually compara ble.4' In animals, serotonin has produced marked rises in pulmonary artery pressure, and this has been noted during human catheterization studies.@@It has been postu lated, therefore, that the anatomic lesions of the heart may be secondary to mechani cal stress. Pulmonary artery pressure was within normal limits in the study of this patient. However, the pulmonary vascular resistance was a low value of 44.6 dyne seconds/cm5. Total pulmonary resistance was within normal limits, 162.2 dyne-see onds/cm5.â€•

An unusual degree of mental disturbance in patients with functioning carcinoid has been commented upon repeatedly. Mac Donald noted in the cases he reported many comments such as, â€œ¿unco-operative,â€• â€œ¿unreliable,â€•â€œ¿contradictory,â€•and â€œ¿very nervous.â€•28 In a group of 38 reported by Mattingly,14 two were confined to psychi atric wards terminally. The observations that administration of 5-hydroxytryptophan to animals produces central disturbances, and that certain psychotropic drugs alter metabolism of serotonin, are evidence that serotonin may have a role in cerebral func tion.1' The personality and attitude of our patient was normal, or perhaps showed more than the usual degree of co-operative ness, reliability, and calmness.

Carcinoids grow slowly, and many cases may originate in infancy and childhood.13'25 Even when metastases to lymph nodes and liver are detected, relatively long periods of survival are to be expected. Survival up to 16 years following surgery for obstruc tion of the small intestine has been noted in older patients.47 The volume of tumor tissue may reach several kilograms. Many of the adults develop congestive heart fail ure associated with lesions of the right side of the heart, but some have developed diar rhea, ascites, and cachexia without evi dence of heart disease at autopsy.13â€•4 X-ray

TABLE IV

WATER DIURESIS TEST IN A 15-YEAR-OLD BOY

WITH FUNCTIONING CARCINOID

Urine Output Specific Graeity (ml)

* Primed with 868 ml tap water (20 mI/kg); 24-hour

5-HIAA excretion: 55.1 mg.

t Primed with 960 ml tap water (20 ml/kg); 24-hour

5-HIAA excretion: 15.7 mg.

5-HIAA which included these samples was moderately elevated to 55.1 mg. Three months later when the 24-hour 5-HIAA was found to be almost normal at 15.7 mg, the test was repeated, and 80% of the load was excreted in the 4-hour period. The spe cific gravity was 1.001 to 1.002.

The patient had no evidence of heart dis ease, and cardiac catheterization was done to obtain base-line data as well as to detect any early changes that might give some clue as to why these patients eventually develop lesions on the right side of the heart. Gobel et al.@' studied one patient with functioning carcinoid and obtained pulmonary and brachial artery blood levels of serotonin that indicated about two-thirds of the serotonin was removed in passage through the lungs. Sjoerdsma et al.42 de tected no difference in pulmonary artery and femoral artery blood values in three patients.

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959

therapy and antineoplastic drugs such as nitrogen mustards and mercaptopurines have not been beneficial. Serotonin antago nists presently available have not been shown to abolish effects of excess circulat ing serotoninâ€•16 The remaining metastases in our patient would be expected to en large slowly. If no effective serotonin an tagonist or selective agent to destroy carci noid tissue is discovered, he will most likely develop heart disease, diarrhea with ca chexia, or recurrent intestinal obstruction within a number of years.

SUMMARY

A review of the literature revealed 19 cases of nonfunctioning gastrointestinal carcinoid tumors reported in the pediatric age group, with the primary site in the appendix in 15 of these. A case of func tioning carcinoid in a 15-year-old white male is reported. Classic signs and symp toms of increased circulating serotonin were observed, except those of the cardiac sys tem.

REFERENCES

1. Oeconomopoulos,C. T.: Argentaffincelltu

mors (carcinoids) of the appendix in chil dren. PEDIATRICS, 27:134, 1961.

2. Foreman, R. C.: Carcinoid tumors: a report of 38 cases. Ann. Surg., 136:838, 1952.

3. Obemdorfer, S.: Karzinoide Tumoren des

DÃ¼nndarms. Frankfurt Z. Path., 1:426, 1907.

4. Rosenblatt, M. B., and Lisa, J. R.: Cancer of the Lung: Pathology, Diagnosis, and Treat ment. New York, Oxford University Press,

1956, p. 263.

5. Cathala, J., et al.: Tumour carcinoide de bronche avec metastase ganglionnaire chez une file de 10 ans. Arch. Franc. Pediat., 17: 816, 1960.

6. Stanford, W. R., et al.: Bronchial adenoma (carcinoid type) with solitary metastasis and associated functioning carcinoid syndrome. Southern Med. J., 51:449, 1958.

7. Warner, R. R. P., and Southern, A. L.: Car

cinoid syndrome produced by metastasizing bronchial adenoma. Amer. J. Med., 24:903, 1958.

8. Dockerty, M. B., et a!.: Metastasizing bron chial carcinoid with hyperserotoninemia and the carcinoid syndrome. Med. Clin. N.

Amer.,42:975,1958.

9. Schneckloth, R. E., Mclsaac, W. M., and Page, I. H. : Serotonin metabolism in carcinoid

syndrome with metastatic bronchial ade

noma. J.A.M.A., 170:1143, 1959.

10. Anlyan, W. G., et al.: Metastasizing bronchial adenoma: occurrence in patient with the

functioning carcinoid syndrome. J.A.M.A.,

174:415,1960.

11. Sjoerdsma, A. : Serotonin. New Engl. J. Med.,

261:181,231, 1959.

12. Isler, Von P., and Hedinger, C. : Metastaser

endes Di.inndarmcarcinoid mit schweren vorweigend das rechte Herz betreffend Klappenfehlem und Pulmonalstenoseâ€”ein eigenartiger Symptomenkomplex? Schweiz. Med. Wschr. 83:4, 1953.

13. Thorson, A., et a!.: Malignant carcinoid of the

small intestine with metastases to the liver, valvular disease of the right side of the

heart (pulmonary senosis and tricuspid re

gurgitation without septal defects), peiiph eral vasomotor symptoms, bronchoconstric

tion, and an unusual type of cyanosis. Amer. Heart J., 47:795-817, 1954.

14. Mattingly, T. W. : The functioning carcinoid tumorâ€”a new clinical entity. Med. Ann. D.

C., 25:304, 1956.

15. Spain, D. M.: Pathophysiology of carcinoid

tumors. Advance Intern. Med., 9:207, 1958. 16.Sauer,W. G.,Dearing,W. H., and Flock,E.

V.: Diagnosisand management of function

ing carcinoids. J.A.M.A., 168:139, 1958. 17. Sjoerdsma, A.: Clinical and laboratory fea

tures of malignant carcinoid. Arch. Intern. Med. 102:936, 1958.

18. Applebauin, H. S.: Functioning carcinoids.

Ohio Med. J.,56:62,1960.

19. Hicks, B., and Kadinski, S.: â€œ¿Carcinoidhi

mourâ€• of a Meckel's diverticulurn. Lancet, 2:70, 1922.

20. Forbus, W. D.: Argentaffine tumors of the ap pendix and small intestine. Bull. Johns Hop kins Hosp., 37:130, 1925.

21. Raiford, T. S.: Carcinoid tumors of the gas

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22. LÃ¼tzow-Holm, C.: Carcinoid tumors of the stomach. Acta Chir. Scand., 104:193, 1952. 23. Webster, R., and Williams, A.: Notes on ar

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24. Kevorkian, J.: Incidence of carcinoid tumors: review of necropsy and surgical specimens at the University of Michigan. Univ. Mich.

Med. Bull., 23:276, 1957.

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intestine: a report of 3 cases with metas

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Amer. J. Surg., 76:434, 1948.

28. MacDonald, R. A.: A study of 356 carcinoids of the gastrointestinal tract. Amer. J. Med., 21:867, 1956.

29. BiÃ¶rck, G., Axen, D., and Thorson, A.: Un

usual cyanosis in a boy with congenital pul monary stenosis and tricuspid insufficiency:

fatal outcome after angiocardiography.

Amer. Heart J.,44:143,1952.

30. Hendrix,T. R., et a!.:Effectof 5-hydroxy

tryptamine on intestinal motor function in man. Amer. J. Med., 23:886, 1957.

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terology, 35:570, 1958.

32. Bornstein,A. M.: Carcinoidtumors:J. Ken

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33. Pearl, W. S., Andrews, T. M., and Robertson,

J. L. S.: Carcinoid syndrome. Lancet, 1:577, 1961.

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35. McNeely, R. G. D., and Jones, N. W.: Sec

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36. Sjoerdsma, A.: Simple test for diagnosis of metastatic carcinoid (argentaffinoma). J.

A.M.A.,159:397,1955.

37. Hanson, A., and Serin, F.: Determination of

5-hydroxyindole acetic acid in urine and its excretion in patients with malignant carci

noid.Lancet,2:1359,1955.

38. Davis, R. B., and Rosenberg, J. C.: Carcinoid

syndrome associated with hyperserotonin

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39. Martin, M. M., and Wilkins, L.: Pituitary dwarfism: diagnosis and treatment. J. Clin. Endocr., 18:679, 1958.

40. Best, C. H., and Taylor, N. B.: The Physio

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Baltimore, Williams & Wilkins, 1961, p. 548.

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5-hydroxytryptamine metabolism in ac

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42. Sjoerdsma, A., et a!.: Further observations on

patients with malignant carcinoid. Amer. J.

Med.,23:5,1957.

43. Robertson, J. I. S., and Andrews, T. M.: Free

serotonin in human plasma. Lancet, 1:578,

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44. McKusick, V. A.: Carcinoid cardiovascular dis

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45. Dexter, L., et a!.: Studies of the pulmonary

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Acknowledgment

We wish to express our gratitude to Dr. Albert Sjoerdsma, National Heart Institute, Bethesda,

Maryland, for furnishing sertonin levels of the

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1962;29;953

Pediatrics

Jack Lavyrl Field, Lucile Frances Adamson and Harry E. Stoeckle

Male