DIGESTIVE D SEASES Chronic Pancreatitis in African Diabetics A.C.B. Wicks, MD, MRCP, and D.J. Clain, MD, MRCP

Steatorrhea due to chronic pancreatitis was found in 23% of a consecutive series of 107 new African diabetics; 3 had pancreatic calcification. Of 16, 14 had definitely abnormal exocrine secretion on pancreatic function testing using secretin-pancreozymin stimulation. The morphology and function of the small intestine were normal by local standards. When compared with diabetics without steatorrhea they weighed less, their fasting blood sugars were lower, and their insulin requirements were greater. High alcoholic intake might be a significant cause, but the incidence was similar in the diabetics without steatorrhea. No evidence of childhood or adult malnutrition was established. The etiology of this high incidence of chronic pancreatitis among African diabetics remains unexplained. A l t h o u g h e x o c r i n e p a n c r e a t i c i n s u f f i c i e n c y is n o t c o m m o n l y f o u n d in p a t i e n t s w i t h d i a b e t e s mellitus (1-4), we have observed an unusually h i g h i n c i d e n c e o f s t e a t o r r h e a in d i a b e t i c s at H a rari African Hospital. In view of this finding, we embarked

on a

p r o s p e c t i v e s t u d y o f all n e w d i a b e t i c w a r d a d missions over a 12-month period. The aim was to e s t a b l i s h t h e i n c i d e n c e a n d c a u s e o f s t e a t o r r h e a , w i t h s p e c i a l r e f e r e n c e to p a n c r e a t i c i n sufficiency. Consideration

was

a l s o g i v e n to

small-intestinal causes of steatorrhea diabetic

neuropathy (5-8)

berculosis, and sprue (9-13).

tropical

and and

s u c h as

incidental

tu-

nontropical

PATIENTS AND M E T H O D S Diabetes was defined according to the criteria laid down by the Medical and Scientific section of the British Diabetic From the Department of Medicine, Harari Hospital, University of Rhodesia, Salisbury. This work formed part of Dr. Wicks' thesis for his M D degree (Birmingham). This work was supported by a generous research grant from the University of Rhodesia. Address for reprint requests: Dr. A.C.B. Wicks, Department of Medicine, Harari Hospital, P.O. Box St. 14, Southerton, Salisbury, Rhodesia.

Digestive Diseases,Vol. 20, No. 1 (January1975)

Association (14). 107 new diabetics were admitted to Harari Hospital over a one-year period; 9 died or were too sick to investigate further, leaving 98 patients who were tested for steatorrhea. Control values for fecal fat excretion, o-xylose excretion, vitamin Bx2 absorption, and jejunal biopsy were obtained from hospital porters and patients who had no evidence of gastrointestinal disease. The diet was supplemented to contain at least 70-80 g fat/day. Fecal fatty acids were measured by the method of van der Kamer (I 5) and expressed as the daily mean of a 5day collection. Steatorrhea was defined as fecal fatty acid excretion exceeding 6 g/day. Pancreatic function testing was carried out by the method of Bank et al (16), using secretin-pancreozymin stimulation with an 80-minute collection of duodenal juice. Amylase was measured in Pimstone units/ml, and the standard bicarbonate was measured in mEq/liters using the Van Slyke apparatus_ The volume was measured in milliliters, and the total protein in milligrams as a reflection of total enzyme content (17). Ten healthy hospital porters acted as control subjects. D-xylose excretion was measured according to the method of Roe and Rice (18) after an oral 25-g xylose load. Vitamin Baz absorption measurement was based on the method of Workman and Rusehe (19). Cobalt-57-1abeled vitamin B,z (Radiochemicals, Amersham) was given orally with intrinsic factor. Blood was withdrawn 8 hours later and the radioactivity measured using a scintillation detector and gamma spectrometer. The result was expressed as a percentage of the administered dose per liter of plasma.

1

W I C K S & CLAIN

20

oe

15

15

:

9 Q9

9

9

9149 e 9149149149

e9

10

10

%. gg.

9

e.

9 9 Q

9

#

.... 9

"~

J

9

eta =lo 9

=o=

ae ee 9

e9

9149149

9

5

+

9149

~149 ~149149

tie 9 ~

et

A

B

C

A

B

C

A

B

C

A

B

C

Fecal fats

D-Xylose

B12 Absorption

Jejunal Biopsy

(g/day)

(g/5 hrs)

('/.liter plasma)

(grading)

Fig 1. Gomparison of fecal fat excretion, D-xylose excretion, vitamin B12 absorption, and jejunal biopsy grading in diabetics with steatorrhea (Column A) and hospital control subjects (Column B), In Column C are a group of Rhodesian African patients from Harari Hospital who have tropical sprue.

Jejunal biopsies were obtained with the Crosby-Kugler capsule (20), using a modified technique to obtain rapid samples (21). The specimens were examined under the dissecting microscope in the fresh state and the mucosa graded according to the predominant villous patterns (1, finger villi; 2, leaves; 3, joined leaves and short ridges; 4, long ridges; 5, convolutions; 6, flat)~ Serum insulin immunoassays were carried out by the method of Hales and Randle (22), following stimulation either by a loading dose of 50 grams glucose orally or in combination with 1 gram of intravenous tolbutamide. Straight x-ray of the upper abdomen was taken in all patients and hypotonic duodenography (23) was performed in 9 patients. All stools were microscopically examined for intestinal parasites by the water centrifugation and sodium chloride flotation method. A careful history of dietary and alcoholic intake was obtained in all patients. The significance of the difference between the groups was tested by Wilcoxen's method.

2

RESULTS Ninety-eight diabetics were tested for steatorrhea. Of these, 23 (24.4%) excreted more than 6 grams of fat per day and are reported in detail below. The remainder excreted less than 6 grams of fat per day and for the purpose of this study were not further investigated for malabsorption. There were 15 males and 8 females, with a mean age of 46.7 years and 35.4 years, respectively. When compared with the 75 diabetics without steatorrhea, they weighed less (P < 0.05) and their fasting blood sugar was lower (P < 0.03), but they required more insulin for control (P < 0.01). Central abdominal pain was common in all the diabetics, but a past history suggestive of acute pancreatitis was Digestive Diseases, Vol. 20, No. 1 (January 1975)

C H R O N I C P A N C R E A T I T I S IN A F R I C A N D I A B E T I C S 3000 12

300 2000

8

8O

200 4i--

100

A

.1,

l

4O

4

-

B

tooo

..~_-

:i"

A B Amylase

Bicarbonate

Volume

Total Protein

(Pimstone units)

(mEq/liter)

(ml)

(mg)

A

B

A

B

Fig 2. Comparison of amylase and bicarbonate production, volume, and total protein in the pooled 80-minute duodenal collection from the diabetics with steatorrhea (Column A) and hospital control subjects (Column B). Values below the dotted line indicates definite abnormality.

found in only one who had pancreatic calcification and steatorrhea. Ketonuria was less frequent in the presence of steatorrhea, but the differences did not reach statistical significance. However, no patient with steatorrhea had a family history of diabetes. Retinopathy, neuropathy, diarrhoea, impotence, and postural hypotension were not seen. Eighteen patients (75 %) were more than 10% below their desirable weight (24), with a third of these patients more than 20% underweight. Two female patients were slightly overweight and three others were normal. The consumption of refined sugar was 79.2 g/day, which was significantly less (P < 0.01) when compared with 101.3 g/day in the diabetic patients without steatorrhea. Dietary protein was more difficult to accurately assess but was poor in the majority of patients questioned. No history of childhood malnutrition was obtained from any of the relatives. Eighty percent of the patients drank homebrewed African beer, which contains 19 g alcohol/liter. Heavy drinking was present in 43% of the steatorrhea patients and was defined arbitrarily as alcohol consumption in excess of 500 ml pure alcohol/week. One patient only drank spirits in addition to beer. A similar number of Digestive Diseases, Vol. 20, No. 1 (January 1975)

patients (50%) were found to be heavy drinkers of African beer in the nonsteatorrhea group of patients. Investigations Of the 23 patients with steatorrhea, 5 refused pancreatic function testing, in 1 there was a technical failure, and 1 was too deeply jaundiced to investigate further; 16 patients were studied in detail. The mean excretion of fecal fat in these patients was no different from the 16 patients studied in detail. Absorption Tests Fecal fat excretion ranged between 6.1 and 20.8 g/day with a mean of 9.5 g/day (Figure 1). The control group of nondiabetic inpatients excreted a mean of 2.12 g/day, which was significantly less (P < 0.01) than the nonsteatorrhea group of diabetics who excreted a mean of 3.08 g/day. A low D-xylose excretion was found in 5 patients, but there was no significant difference from the controls. One patient had a low B12 absorption test. Apart from the biopsy grading of 4 in one patient with pancreatic calcification, the remaining grades fell within normal local limits (25). 3

WICKS & CLAIN

Fig 3, Extensive pancreatic calcification on a post-mortem specimen from a diabetic patient who died soon after admission,

The results of the pooled 80-minute duodenal collection are shown in Figure 2. The control subjects were not different from the normal values obtained by Bank et al (16), and therefore we have adopted their criteria for abnormality: bicarbonate level below 60 m E q / liter (borderline 60-67 mEq/liter); an amylase concentration below 5 Pimstone units/ml (borderline 5-6 Pimstone units/ml); volume below 100 ml (borderline 100-140 ml). If two borderline results occurred together, this was considered to be an abnormal test. The total protein content has a wide range of values and interpretation is more difficult, but as a whole the diabetic patients had significantly less protein than the controls (P < 0.02). Fourteen patients were definitely abnormal, and two were normal, according to the criteria above. The majority of Rhodesian African diabetics 4

are insulinopenic (26). Although a lower response was obtained in patients with steatorrhea than in the nonsteatorrhea group, this did not reach statistical significance. Only one good insulin response occurred, in a patient with pancreatic calcification. Three patients were found to have pancreatic calcification on straight x-ray of the abdomen. Of the nine patients in whom hypotonic duodenography was performed, three showed definite abnormality, with an elongated duodenal loop, and pancreatic calcification. No intestinal parasites were found, but cysts of E. coli were detected in ten patients and Giardia lamblia in two others. There were ova of S. rnansoni and hookworm in three and four patients respectively. Three male patients, aged 40, 41, and 44, had pancreatic calcification on abdominal xDigestive Diseases, Voi. 20, No. 1 (January 1975)

CHRONIC PANCREATITIS IN AFRICAN DIABETICS

ray. Three other patients, two males and one female, all over the age of 40, had hepatic cirrhosis with hemosiderosis and porphyria cutane tarda. The female patient was deeply jaundiced with grossly abnormal liver function tests, and she was not further investigated. Eighteen patients (78%) required an average of 72 units of insulin a day, compared with 57 units of insulin in the nonsteatorrhea group (77%). The percentage of patients requiring insulin in the two groups was not statistically different, but the amount of insulin required was greater in the steatorrhea group (P < 0.01). DISCUSSION

This investigation of a consecutive series of 107 new African diabetics has shown a 23% incidence of steatorrhea due to chronic pancreatic insufficiency. The pattern of gastrointestinal investigation is consistent with fibrosis due to chronic pancreatitis. One patient in the series, who came to autopsy, demonstrated the typical histological features of chronic pancreatitis with calcification (Figure 3). Three other diabetics showed pancreatic calcification on abdominal x-ray. The pancreatic origin of the steatorrhea was confirmed by abnormal pancreatic function tests,- after pancreozymin-secretin stimulation, and by the absence of small-intestinal causes of malabsorption. The D-xylose excretion, Co57B12 absorption, and jejunal biopsies were normal for this population. In previous studies of normal Africans, we have shown a high incidence of minor abnormalities of jejunal morphology and D-xylose excretion, similar to the results in surveys of apparently normal members of the native-born populations of Thailand (27), south India (28), Puerto Rico (29), southwest Pakistan (30), and Uganda (31). The diabetics with steatorrhea in this study and our control population are not significantly different (25). However, there were clear-cut differences in jejunal morphology and in the absorption tests between the diabetics with steatorrhea due to Digestive Diseases, Vol. 20, No. 1 (January 1975)

pancreatic insufficiency and a group of patients seen here with megaloblastic anemia and steatorrhea who are indistinguishable from cases of tropical sprue (32) (Figure 1). No patients had diarrhea or evidence of diabetic autonomic neuropathy to account for their steatorrhea. Regional enteritis has never been seen in a Rhodesian African. Parasitic infections such as hookworm (33) and giardiasis (32) have been shown in this country not to be sufficiently heavy to produce either anemia or malabsorption. We have been unable to compare the incidence of steatorrhea in our diabetics with those in other tropical and temperate zones, as we are unaware of a similar consecutive series of diabetics in whom fecal fat excretion has been studied. There are other African countries where primary pancreatic disease, with or without calcification, is associated with a high prevalence of diabetes (34-36). Pancreatic calcification has been well described in Uganda (36), Nigeria (37), and the Congo Republic (38). Single cases have been reported from Malawi (39), Tanzania (40), and Rhodesia (41). In temperate zones, pancreatic exocrine abnormalities have been demonstrated in a high percentage of randomly selected diabetes following stimulation by secretin and pancreozymin (4244). The presence of steatorrhea due to chronic pancreatic disease in almost one-quarter of our series of diabetics is more remarkable in view of the difficulty in establishing a common cause such as alcoholism or cholelithiasis. While alcohol is a major cause of chronic pancreatitis in France (45), the United States (46), the United Kingdom (47), and in Cape Town (48), its role in Africans is not clear. Forty-three percent of the patients with steatorrhea were heavy drinkers of African beer, but this was not significantly greater than those diabetic patients without steatorrhea. Shaper (36) in Uganda found a similar incidence, which he discounted because of the large number of very young patients. He fa5

WICKS & CLAIN

vored the explanation of malnutrition as the prime factor. Kinnear (37) and Olurin and Olurin (49) in Nigeria, Sonnet et al (38) in the Congo, Zuidema (50) in Indonesia, all dismissed alcohol as the main factor and supported malnutrition as an explanation, but with little objective evidence. In a review of 7 Rhodesian African patients with pancreatic calcification (51), 6 were heavy drinkers of homebrewed beer, but none took wine or spirits. There was also a girl of 12 who had never drunk alcohol. Apart from a female of 50, all were diabetic. D e s p i t e careful q u e s t i o n i n g of all the patients' relatives, there was no evidence of childhood malnutrition, although the accuracy of this information is open to doubt. The gross pancreatic changes which occur in kwashiorkor appear to recover after treatment (52). Barbezat (53) showed that exocrine pancreatic function returned to normal after kwashiorkor but not in children who had been chronically malnourished and marasmic. Banwell and Campbell (54) on retesting exocrine function in two adult patients with protein calorie malnutrition also found an abnormal response suggesting permanent pancreatic dysfunction. Acute pancreatitis rarely proceeds to chronic pancreatic disease (45) and only one patient with steatorrhea gave a past history of acute pancreatitis. However, in the 7 Rhodesian African patients described with pancreatic calcification (51), 3 had had a past episode, although acute pancreatitis is an uncommon disease at Harari Hospital (55), and only 20 cases have been seen over the three-year period 19691971. We have never seen relapsing pancreatitis in an African, although it is frequently seen in the white population. Gallstones and biliary stones are rare in Rhodesian Africans (56) and, like acute pancreatitis, played no obvious role in the pathogenesis of pancreatitis in this study. Bartholomew and Comfort (57) described the clinical entity of painless pancreatitis occurring in patients with steatorrhea, pancreatic calcification, and diabetes, and this 6

sequence is compatible with some of the cases in our series. Hemosiderosis and the association with diabetes has been well documented in Africa (5860). T h e initial results of our investigations suggest that hemosiderosis, which is commonly seen in Rhodesian Africans (61), is a coincidental finding. The data from these investigations are reported separately (62). Reports of the association of pancreatic schistosomiasis with diabetes (49, 63) are probably coincidental. In Harari Hospital we have never seen the combination of pancreatic fibrosis, diabetes, and ova of S. mansoni at autopsy. T h e part played by African herbs and medicine is conjectural but probably warrants further investigations. Although not previously recognized, this study has shown that chronic pancreatic disease is a common cause of diabetes in Rhodesian Africans. T h e etiology is not apparent; alcohol may be significant. T h e role of malnutrition in childhood is uncertain, as there have been no long-term prospective studies of pancreatic damage in malnourished children. ACKNOWLEDGMENTS

We would like to thank Professor M. Gelfand, Dr. E. Taube, and Dr. J.I. Forbes for permission to study their patients, and the Secretary for Health (Rhodesia) for access to patients in Harari Hospital. We are particularly grateful to ProfessorS. Bank and Dr. I.N. Marks in Cape Town for their technical help and advice in the initial stages of this project. ProfessorJ.J. Jones gave valuable statistical advice. Dr. K. Gadd and his staff at the Public Health Laboratory and Miss C. Handke in the Department of Physiology kindly performed bicarbonate and protein estimations, respectively, in the duodenaljuice aspirations. Mr. E. Kanengoniin the Department of Physiology assayed the serum insulin.

REFERENCES

1. Berge KG, Wollaeger EE, Scholz DA, Rooke ED, Sprague RG: Steatorrhea complicating diabetes mellitus with neuropathy. Report of cases without apparent external pancreatic insufficiency. Diabetes 5:25-31, 1956 Digestive Diseases, Vol. 20, No. 1 (January 1975)

CHRONIC PANCREATITIS IN AFRICAN DIABETICS

2. Malins JM, French JM: Diabetic diarrhea. QJ Med 26:467-480, 1957 3. Joslin EP, Root HF, White P, Marble A: The treatment of diabetes mellitus. 10th Edition. London, Lea and Fibiger, 1959 4. Wruble LD, Kalser MH: Diabetic steatorrhea: A distinct entity. Am J Med 37:118-129, 1964 5. Finlay JM: Small-bowel complications of diabetes. Gastroenterology 48:816, 1965 6. Aktan HS, Klotz AP: Fat absorption and pancreatic function in diabetes mellitus. Ann Intern Med 49:820-829, 1958 7. Corsini G, Gandolfi E, Bonechi I, Cerri B: Fat absorption in diabetes mellitus. Diabetes 16:455-461, 1967 8. Whalen GE, Soergel KH, Geenen JE: Diabetic diarrhea: A clinical and pathological study. Gastroenterology 56:102 I-1032, 1969 9. Mailman RH: Steatorrhea with diabetes: A case report. Ann Intern Med 49:190-192, 1958 10. Taxay EP, Roath S, Mitchel S: Malabsorption syndrome and diabetes mellitus. Diabetes 9:106-109, 1960 11. Ellenberg M, Bookman J J: Diabetic diarrhea with malabsorption syndrome. Diabetes 9:1416, 1960 12. Vinnik IE, Kern F, Struthers JE: Malabsorption and the diarrhea of diabetes mellitus. Gastroenterology 43:507-520, 1962 13. Green PA, Wollaeger EE, Sprague RG, Brown AL: Diabetes meltitus associated with non-tropical sprue. Diabetes 11:388-392, 1962 14. Fitzgerald MG, Keen M: Diagnostic classification of diabetes. Br Med J 1:1568, 1964 15. van de Kamer JH, ten Bokkel H, Weyjers HA: Rapid method for the determination of fat in feces. J Biol Chem 177:347-355, 1949 16. Bank S, Marks IN, Moshal MG, Efron G, Silbet R: The pancreatic function test--Method and normal values. S Afr Med J 37:1061-1066, 1963 17. Hanscom DH, Jacobson BM, Littman A: The output of protein after pancreozymin: A test of pancreatic function. Ann Intern Med 66:721726, 1967 18. Roe JH, Rice EW: A photometric method for the determination of pentoses in animal tissues. J Biol Chem 173:507-512, 1948 19. Workman JB, Rusche E: Cobalt 57 labelled Vitamin Blz plasmin levels for the differential diagDigestive Diseases, Vol. 20, No. 1 (January 1975)

nosis of macrocytic anaemias. J Nucl Med 7:583-588, 1966 20. Crosby WH, Kugler HW: Intraluminal biopsy of the small intestine: The intestinal biopsy capsule. A m J Dig Dis 2:236-241, 1957 21. Wicks ACB, Clain D J: A guide wire for rapid jejunal biopsies with the Crosby capsule. Gut 13:571, 1972 22. Hales CN, Randle P J: Immunoassay of insulin with insulin antibody precipitate. Biochem J 88:137-146, 1963 23. Bilbao MK, Frische LH, Dotter CT: Hypotonic duodenography. Radiology 89:438-443, 1967 24. Doeumenta Geigy (7th Edition) Basel, 1970 p 711 25. Clain D J: Malabsorption in Rhodesian Africans with special reference to tropical sprue. Paper presented to the joint biennial congress of the Association of Physicians of South Africa, Johannesburg, 1968 26. Wicks ACB, Jones J J: Insulinopoenic diabetes in Africa. Br Med J 1:773-776, 1973 27. Sprinz H, Sribhibhadh R, Gangarosa E J, Benyajati C, Kundel D, Halstead S: Biopsy of small bowel in Thai people. Am J Clin Pathol 38:4351, 1962 28. Lindenbaum J, Alam AKMJ, Kent TH: Subclinical small intestinal diseases in East Pakistan. Br Med J 2:1616-1619, 1966 29. Robins SJ, Garcia-Palmieri M, Rubio C: Low serum cholesterol levels and subclinical malabsorption. Ann Intern Med 66:556-567, t967 30. Russell PK, Aziz MA, Ahmad N, Kent TH, Gangarosa E J: Enteritis and gastritis in young asymptomatic Pakistani men. Am J Dig Dis 11:296-306, 1966 31. Banwell JG, Hutt MSR, Tunnicliffe R: Observations on jejunal biopsy in Ugandan Africans. E Afr Med J 41:46-54, 1964 32. Thomas GE, Clain D J: Tropical sprue in Rhodesian Africans. In preparation, 1974 33. Gelfand M, Warburton B: The species of hookworm and degree of egg load in Rhodesia. Trans R Soc Trop Med Hyg 61:538-543, 1967 34. Banwell JG, Hutt MRS, Leonard P j, Blackman V, Connor DW, Marsden PD, Campbell J: Exocrine pancreatic disease and the malabsorption syndrome in tropical Africa. Gut 8:388401, 1967 35. Banwell JG, Campbell J, Blackman V, Hurt 7

WICKS & CLAIN

36.

37.

38.

39.

40.

41.

42.

43.

44.

45.

46. 47. 48.

8

MV, Leonard P: Studies of intestinal function in Ugandan diabetic patients. E Afr Med J 40:277-287, 1963 Shaper AG: Aetiology of chronic pancreatic fibrosis with calcification seen in Uganda. Br Med J 1:1607-1609, 1964 Kinnear TWG: The pattern of diabetes mellitus in a Nigerian teaching hospital. E Afr Med J 40:288-294, 1963 Sonnet J, Brisbois P, Bastin JP: Chronic pancreatitis with calcification in Congolese Bantus. Trop Geogr Med 18:97-113, 1966 Goodall JWD, Pilbeam STHH: Diabetes in Malawi. Trans R Soc Trop Med Hyg 58:575578, 1964 Haddock DRW: Diabetes mellitus and its complications in D a r e s Salaam. E Afr Med J 41:145-155, 1964 Gelfand M, Cart WR: Diabetes metlitus in Africans in Rhodesia. Cent Afr Med J 7:41-48, 1961 Chey WY, Shay H, Shuman CR: External pancreatic secretion in diabetes mellitus. Ann Intern Med 59:812-821, 1963 Vacca JB, Henke, W J, Knight AW: The exocrine pancreas in diabetes mellitus. Ann Intern Med 61:242-247, 1964 Bock AA, Bank S, Marks IN, Jackson WPU: Exocrine pancreatic function in diabetes mellitus. S Afr Med J 41:756-758, 1967 Sarles H, Sarles JC, Camatte R, Muratore R, Gaini M, Guien J, Leroy F: Observations on 205 confirmed cases of acute pancreatitis, recurring pancreatitis and chronic pancreatitis. Gut 6:545-559, 1965 Howard JM, Jordon GL: Surgical diseases of the pancreas. Philadelphia, Lippincott, 1960 Howat HT: Chronic pancreatitis: Medical aspects. Postgrad Med J 44:733-736, 1968 Marks IN, Bank S: The aetiology, clinical features and diagnosis of pancreatitis in the South

49. 50.

51.

52. 53.

54.

55.

56.

57.

58.

59.

60. 61. 62.

63.

West Cape. A review of 243 cases. S Afr Meal J 37:t039-1053, 1963 Olurin EO, Olurin O: Pancreatic calcification. A report of 45 cases. Br Med J 4:534-539, 1969 Zuidema P J: Cirrhosis and disseminated calcification of the pancreas in patients with malnutrition. Trop Geogr Med 11:70-74, 1959 Wicks ACB: Pancreatic calcification in Rhodesian Africans. Cent Aft Med J 19:189-193, 1973 Davies JNP: The essential pathology of Kwashiorkor. Lancet 1:317-320, 1948 Barbezat GO: The exocrine pancreas and protein calorie malnutrition. S Afr Med J 41:84, 1967 Banwell JG, Campbell J: Pancreatic exocrine function in African patients. Trans R Soc Trop Med Hyg 61:390-398, 1967 Wicks ACB, Flemming JBM: Acute panereatitis in Rhodesian Africans. Cent Aft Med J 20:115-119, 1974 Wicks ACB, Holmes GS, Davidson L: Endemic typhoid fever. A diagnostic pitfall. QJ Med 40:341-354, 1971 Bartholomew LG, Comfort MW: Chronic pancreatitis without pain. Gastroenterology 31:727-745, 1956 Seftel HC, Isaacson C, Bothwell TH: The relationship between siderosis and diabetes in the Bantu. S Afr J Med Sci 25:89-98, 1960 Dodu SRA: Diabetes and haemosiderosis-Haemochromatosis in Ghana. Trans R Soc Trop Med Hyg 52:425-430, 1958 Haddock DRW: Bantu siderosis in Tanzania. E Afr Med J 42:67-73, 1965 Buchanan WM: Siderosis in Rhodesian Africans. Cent Aft J Med 15:105-113, 1969 Wicks ACB, Lowe R, Jones J J: Alcohol and diabetes in Rhodesian Africans. S Aft Med J 48:1115-1117, 1974 Bibawi E: Schistosomiasis and diabetes mellitus. Trans R Soc Trop Med Hyg 64:907-908, 1970

Digestive Diseases, Voi. 20, No. 1 (January 1975)