83

received parasympathetic drugs. Baar 20 failed to pro-duce any changes in the pancreas of rats and guineapigsby sustained injections of parasympathetic drugs ; whileWener et al.29 found that injection into dogs of methyl-choline was followed by hypersomia of the pancreas,interstitial haernorrhages, and fat necrosis, but no changesresembling fibrocystic disease. The whole idea is

incompatible with known facts of physiology. There isno antagonism between cholinergic and adrenergicsystems so far as pancreatic secretion is concerned.Babkin et al.3o have shown that splanchnic stimulationproduces only slight pancreatic secretion, and thissecretion is of the same type as that from vagal stimula-tion. Secretion is inhibited by atropine and potentiatedby eserine, but not by injections of adrenaline ; it istherefore due to cholinergic fibres in the splanchnicnerve. Recently, contrary to Farber’s theory of hyper-function of parasympathetic system, hypofunction hasbeen assumed.31 Splanchnicectomy was recommendedin fibrocystic disease of the pancreas by Ayers et allbut later these workers 33 concluded that this proceduredoes not cure. The operation has no physiological basis.A disturbance of the balance between secretin and

parasympathetic stimuli was suggested by Baar, andlater independently by Bagenstoss 34 ; but Bagenstosssubsequently extracted secretin from the intestinal wallin children with fibrocystic disease of the pancreas 35and thus disproved the hypothesis.

Several workers have sought to explain fibrocysticdisease of the pancreas as a genetically determinedmalformation of the duct system 9 or hypoplasia ofterminal ductules.22 Werthemann et al.9 describe splittingof main pancreatic ducts; Bodian found in serialsections isolated cysts, dilated spaces communicatingwith the duct system, narrowing of smaller ducts, andoccasionally only duct atresia ; while in some cases theducts were abnormal only in respect of the nature ofthe contents. Wissler and Zollinger, on the other hand,found in none of the 8 cases where they examined serialsections any narrowing or obliteration of the larger

.

ducts ; and the ductules were usually normal. It must,z however, be realised that the only reliable method is

plastic reconstruction. This extremely laborious tech-nique has been carried out only on two occasions-byWurm 36 and by Norris and Tyson,37 who found isolatedcysts and dilated spaces in connection with the ductsystem. Werthemann et al. rightly point out that thesefindings give no information about the cause of the

disorder; they only indicate a secondary segregationin a developed duct system. Plastic reconstruction

-especially that of Norris and Tyson-proves that

segregation has taken place after the duct systemdeveloped, but the cause may have been a developmental

, error, or intra-uterine inflammation, or atrophy followed! by replacement fibrosis. The frequency of malformations

! in organs is cited as evidence that fibrocystic disease ofj the pancreas is due to a malformation of the duct system.1 But if such " malformations " as patent foramen ovalef and patent ductus arteriosus in an infant 11/2 months of

age, inguinal testicle, caecum mobile, and pyloric stenosis: are excluded and if dysontogenetic cystosis of the pan-t creas is distinguished from fibrocystic disease, theref remain only changes in the biliary-duct system as a

! common finding ; and these changes may or may not

29. Wener, J., Simon, M. A., Hoff, H. E. Gastroenterology, 1950,15, 125.

30. Babkin, B. P., Hebb, C. O., Sergeyeva, M. A. Quart. J. exp.Physiol. 1939, 29, 217.

31. Bergstrand, H. Acta pœdiat., Stockh. 1951, 40, 349.32. Ayers, W. B., Stowens, D., Ochsner, A. J. Amer. med. Ass.

1950, 142, 7.33. Ayers, W. B., Stowens, D., Ochsner, A., Platou, R. V. Pedia-

trics, 1951, 8, 657.34. Bagenstoss, A. H. Arch. Path. 1948, 45, 463.35. Bagenstoss, A. H., Power, M. H., Grindley, J. H. Ibid, 1951,

51, 510.36. Wurm, H. Z. Kinderheilk. 1927, 43, 286.37. Norris, R. F., Tyson, R. M. Amer. J. Path. 1947, 23, 485.

be due to developmental malformation. The fact thatthe appearance of pancreatic ducts in serial sectionsvaries from case to case and from segment to segment,in some cases with segregation, and in others withdeformity, while in some areas there may be atrophywith structurally normal ducts, is strong evidence againsta structural malformation as the fundamental lesion.If, however, the idea of malformation is taken in a

wider sense, including an inherited functional abnormalityof one or more derivatives of the midgut, we have anattractive hypothesis which would cover the known

pathological findings, but which is difficult to prove.Fibrocystic disease would be an interesting example ofa heredo-degenerative disease in a system other thanthe central nervous system. Changes in the pancreasvary in severity, and it is quite conceivable that,depending on chromosomal environment, the same geneleads either to structural and functional maldevelopmentor to functional maldevelopment only.

Experimental work has contributed little to theelucidation of the problem. Ligature of the pancreaticducts results in atrophy with replacement fibrosis or

lipomatosis, or in a duct condition known as " ranulapancreatica," 38-41 but not in changes comparable with

’ fibrocystic disease of the pancreas. The experiments ofFarber were not confirmed by other workers ; and thechanges were mild, resembling more the pancreatosisdescribed by Bagenstoss in uraemia than true fibroeysticdisease. In recent years Veghelyi and his associates 42have described the production of fibrocystic disease ofthe pancreas in rats by dietary means, and by injectionsof carbon tetrachloride and paradysentery toxin. Theanimals showed also severe pulmonary changes whichresembled those in infantile fibrocystic disease of the

pancreas. None of these noxious agents can be blamedfor the disease in infants, but the experiments are ofgreat interest because they show that various causescan produce fibrocystic changes in the pancreas, andparticularly because, whatever was the cause, the changeswere associated with mucous hypersecretion of bronchialepithelium, peribronchitis, bronchial destruction, andfibrosis. Genetic research has shown that we mustassume a single cause for fibrocystic disease of the

pancreas, but the cause is still unknown.H. S. BAAR.H. S. BAAR.

38. Gruber, G. G. In Handbuch der speziellen pathologischenAnatomie und Histologie. Berlin, 1929 ; vol. 5, part 2.

39. Hess, O. Mitt. Grenzgeb. Med. Chir. 1907, 19, 367.40. Gross, O., Gulecke, N. Die Erkrankungen des Pancreas.

Berlin, 1924.41. Greenberg, J. Yale J. Biol. Med. 1933, 6, 121.42. Véghelyi, P. V., Kemény, T. T., Sos. J., Amer. J. Dis. Child.

1950, 79, 65, 846 ; Ibid, 80, 390.

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