1
489 by WARREN 5 76% of the cases started with gastro- intestinal symptoms and in a fifth of these they were the only symptoms. Such figures are exceptional but they add point to SAVAGE’S views. Many of the older writings on the disease are invalidated by their failure to distinguish between Bacterium paratypho8um B and other salmonellas, particularly Bact. typhi murium (B. certrycke). SAVAGE, emphasising the relationship, postulates a recent common origin for these organisms. In its evolution the paratyphoid bacillus has acquired some. of the ihvasiveness of the typhoid bacillus while retaining some of the intestinal irritant properties of the salmonelhe. This point is further elaborated in SAVAGE’s discussion of the variable incubation period of the disease. During incubation the organisms multiply in the mesenteric lymph-nodes, the liver and the spleen. With the onset of the disease a bactereemia occurs. Positive blood-cultures can be obtained in 90% of cases in the first week, 75% in the second week and 60% in the third week. The recovery of the organism from the stools in greatest numbers during the second week is not due to their multiplica- tion in the bowel but to their being excreted partly in the bile. On the other hand, food-poisoning is a 5. Warren, S. H. Publ. Hlth, 1941, 54, 139. purely enteral infection and invasion of the blood, except as a terminal event, is rare. SAVAGE finds here an explanation of the relatively long incubation period of the enteric fevers and contrasts it with the short period for food-poisoning and for the gastro- intestinal symptoms of paratyphoid fever. This speculation is worthy of further investigation : if there is any substance in it, cases of paratyphoid fever without enteric symptoms should have no bactereemia. KAUFFMANN 6 regards the enteric and gastro-intestinal forms of the disease as - due to different strains of the organism. The classical bacillus does not ferment d-tartrate and produces a mucous wall around agar colonies, whereas strains causing gastro-enteritis ferment d-tartrate-and do not produce the mucous wall. This appears to be a fundamentally different view from that of SAVAGE, who regards the classical paratyphoid bacillus as a recent variant from other salmonellee. Except for its occasional invasion of dogs it has become almost an obligatory human parasite, albeit one which does not readily infect man. So impressed is SAVAGE with the view that Bact. paratypho8um,B is a true salmonella that he attributes its epidemiological behaviour to this relationship. 6. Kauffmann, F. Die Bakteriologie der Salmonella Gruppe, Copenhagen, 1941. Annotations COMFREY. MAGGOTS AND UREA IN 1912 Dr. C. J. Macalister, stimulated by the story 1 of the disappearance of a nasal sarcoma under poultices of comfrey root, set out to investigate the properties of the common comfrey of our ditches and dunghills. This comely but bristly herb, rightly eschewed by cattle, had been held in high esteem in rural England since Saxon times as a specific for wound healing. Macalister 3 had extracts of the root analysed by Mr. A. W. Titherley, D.Sc., who found that they contained a relatively high pro- portion of allantoin. He used both crude extracts of the root and solutions of pure allantoin to treat a series of chronic ulcers that had failed to respond to other forms of therapy, and was convinced of their efficacy. He was cautious in drawing conclusions, too. " One is rather apt," he says, " when experimenting with a substance in this way, to allow optimism to exaggerate the resultant benefits, and it is an advantage to get others to form an independent judgment concerning them from their own observations " 4-words which might be taken to heart at the present day. Nevertheless he was convinced that he had found a cell proliferant, if only for the reason that gr. 6 of allantoin taken in divided doses over a period of six hours would run his own white cells from 6000 up to 15,000 or more per c.mm. William Bramwell,5 also of Liverpool, suggested that comfrey dressings suc- ceeded because they set hard and adhered closely to the skin. Allantoin had been known since 1821, when it was found, not in sausages as the classically minded might imagine, but in the allantoic fluid of cows. It occurs in many plants and is a normal constituent of the urine of all mammals, where it is an end-product of purine metabolism. Man and the Dalmatian coach- hound share the distinction of having none in the urine except what they have eaten ready made. It is glyoxyl- diureide, C4H6OsN 4’ Allantoin appeared again in sur- gical writings after it had been shown tp be present in 1. Thomson, W. Lancet, 1896, ii, 1507. 2. The Latin name of the genus Symphytum bears testimony to this reputation. 3. An Ancient Remedy and its Modern Utilities, London, 1936. 4. Brit. med. J. 1912, i, 10. 5. Ibid, p.12. the excretions of maggots for military surgeons have acknowledged the benefits of maggot infestation in severe wounds for as far back as records extend. Further examination of the action of allantoin suggested that its action in accelerating wound healing arose from its ability to break down and form urea.7 Urea had earlier been shown to assist the healing of infected wounds and ulcers, though how it does so remains doubtful. W. Ramsden demonstrated in 1902 that proteins dissolve in strong solutions of urea, and that weaker solutions hasten the action of proteolytic enzymes ; the clue may lie there. More recent studies of the action of allantoin on healing processes have not been encouraging ; Chu,8 in fact, found that far from accelerating the growth of epithelial cells solutions of allantoin retarded their multiplication in vitro, and the Council on Pharmacy and Chemistry in the USA thought there was insufficient evidence in 1938 to accept commercial preparations of allantoin as healing agents. Lately allantoin has been mixed with sulphanilamide for application to raw sur- faces, but the efficacy of this traditional remedy has yet to be placed on a firm basis. - PROGNOSIS AFTER PERFORATION THERE is a widespread impression that if a patient recovers after operation for a perforated peptic ulcer he has a good prospect of a lasting cure of the ulcer. Writing in 1918, D. C. Balfour of the Mayo Clinic referred to the " clinical fact ... now generally recognised ... that perforation of a gastric ulcer is quite likely to be followed not only by the cure of the ulcer but by the cure of the patient." This optimistic view moreover is based on the assumption that nothing more than simple closure of the perforation has been done. No explanation seems to have been offered, but it might be supposed that a patient who has once perforated will thereafter be more likely to remember his physician’s advice and take care with his diet and ways of life. In this way an acute catastrophe in an ulcer may prove a lasting blessing, but its moral effect will be lost if the popular error is allowed to persist that once an ulcer has perforated there will be no more trouble. For this reason, if for no other, careful 6. Robinson, W. J. Bone Jt Surg. 1935, 17, 267. 7. Robinson, W. Amer. J. Surg. 1936, 33, 192. 8. Chu, H. J. Proc. Soc. exp. Biol. N.Y. 1938, 38, 99.

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Page 1: COMFREY. MAGGOTS AND UREA

489

by WARREN 5 76% of the cases started with gastro-intestinal symptoms and in a fifth of these they werethe only symptoms. Such figures are exceptionalbut they add point to SAVAGE’S views. -

Many of the older writings on the disease are

invalidated by their failure to distinguish betweenBacterium paratypho8um B and other salmonellas,particularly Bact. typhi murium (B. certrycke). SAVAGE,emphasising the relationship, postulates a recentcommon origin for these organisms. In its evolutionthe paratyphoid bacillus has acquired some. of theihvasiveness of the typhoid bacillus while retainingsome of the intestinal irritant properties of thesalmonelhe. This point is further elaborated inSAVAGE’s discussion of the variable incubation periodof the disease. During incubation the organismsmultiply in the mesenteric lymph-nodes, the liverand the spleen. With the onset of the disease abactereemia occurs. Positive blood-cultures can beobtained in 90% of cases in the first week, 75% in thesecond week and 60% in the third week. The recoveryof the organism from the stools in greatest numbersduring the second week is not due to their multiplica-tion in the bowel but to their being excreted partlyin the bile. On the other hand, food-poisoning is a

5. Warren, S. H. Publ. Hlth, 1941, 54, 139.

purely enteral infection and invasion of the blood,except as a terminal event, is rare. SAVAGE findshere an explanation of the relatively long incubationperiod of the enteric fevers and contrasts it with theshort period for food-poisoning and for the gastro-intestinal symptoms of paratyphoid fever. This

speculation is worthy of further investigation : ifthere is any substance in it, cases of paratyphoidfever without enteric symptoms should have no

bactereemia. KAUFFMANN 6 regards the enteric andgastro-intestinal forms of the disease as - due todifferent strains of the organism. The classicalbacillus does not ferment d-tartrate and produces amucous wall around agar colonies, whereas strainscausing gastro-enteritis ferment d-tartrate-and do notproduce the mucous wall. This appears to be a

fundamentally different view from that of SAVAGE,who regards the classical paratyphoid bacillus as arecent variant from other salmonellee. Except forits occasional invasion of dogs it has become almostan obligatory human parasite, albeit one which doesnot readily infect man. So impressed is SAVAGE withthe view that Bact. paratypho8um,B is a true salmonellathat he attributes its epidemiological behaviour tothis relationship.6. Kauffmann, F. Die Bakteriologie der Salmonella Gruppe,

Copenhagen, 1941.

Annotations

COMFREY. MAGGOTS AND UREA

IN 1912 Dr. C. J. Macalister, stimulated by the story 1of the disappearance of a nasal sarcoma under poulticesof comfrey root, set out to investigate the properties ofthe common comfrey of our ditches and dunghills. This

comely but bristly herb, rightly eschewed by cattle, hadbeen held in high esteem in rural England since Saxontimes as a specific for wound healing. Macalister 3 hadextracts of the root analysed by Mr. A. W. Titherley, D.Sc.,who found that they contained a relatively high pro-portion of allantoin. He used both crude extracts of theroot and solutions of pure allantoin to treat a series ofchronic ulcers that had failed to respond to other formsof therapy, and was convinced of their efficacy. He wascautious in drawing conclusions, too. " One is ratherapt," he says, " when experimenting with a substancein this way, to allow optimism to exaggerate the resultantbenefits, and it is an advantage to get others to form anindependent judgment concerning them from their ownobservations " 4-words which might be taken to heartat the present day. Nevertheless he was convinced thathe had found a cell proliferant, if only for the reasonthat gr. 6 of allantoin taken in divided doses over aperiod of six hours would run his own white cells from6000 up to 15,000 or more per c.mm. William Bramwell,5also of Liverpool, suggested that comfrey dressings suc-ceeded because they set hard and adhered closely tothe skin. Allantoin had been known since 1821, whenit was found, not in sausages as the classically mindedmight imagine, but in the allantoic fluid of cows. Itoccurs in many plants and is a normal constituent of theurine of all mammals, where it is an end-product ofpurine metabolism. Man and the Dalmatian coach-hound share the distinction of having none in the urineexcept what they have eaten ready made. It is glyoxyl-diureide, C4H6OsN 4’ Allantoin appeared again in sur-gical writings after it had been shown tp be present in1. Thomson, W. Lancet, 1896, ii, 1507.2. The Latin name of the genus Symphytum bears testimony to this

reputation.3. An Ancient Remedy and its Modern Utilities, London, 1936.4. Brit. med. J. 1912, i, 10. 5. Ibid, p.12.

the excretions of maggots for military surgeons haveacknowledged the benefits of maggot infestation in severewounds for as far back as records extend. Furtherexamination of the action of allantoin suggested that itsaction in accelerating wound healing arose from its

ability to break down and form urea.7 Urea had earlierbeen shown to assist the healing of infected wounds andulcers, though how it does so remains doubtful.W. Ramsden demonstrated in 1902 that proteins dissolvein strong solutions of urea, and that weaker solutionshasten the action of proteolytic enzymes ; the clue maylie there. More recent studies of the action of allantoinon healing processes have not been encouraging ; Chu,8in fact, found that far from accelerating the growth ofepithelial cells solutions of allantoin retarded their

multiplication in vitro, and the Council on Pharmacy andChemistry in the USA thought there was insufficientevidence in 1938 to accept commercial preparations ofallantoin as healing agents. Lately allantoin has beenmixed with sulphanilamide for application to raw sur-faces, but the efficacy of this traditional remedy has yetto be placed on a firm basis. -

PROGNOSIS AFTER PERFORATION

THERE is a widespread impression that if a patientrecovers after operation for a perforated peptic ulcer hehas a good prospect of a lasting cure of the ulcer. Writingin 1918, D. C. Balfour of the Mayo Clinic referred to the" clinical fact ... now generally recognised ... that

perforation of a gastric ulcer is quite likely to be followednot only by the cure of the ulcer but by the cure of thepatient." This optimistic view moreover is based on theassumption that nothing more than simple closure of theperforation has been done. No explanation seems tohave been offered, but it might be supposed that a

patient who has once perforated will thereafter be morelikely to remember his physician’s advice and take carewith his diet and ways of life. In this way an acutecatastrophe in an ulcer may prove a lasting blessing, butits moral effect will be lost if the popular error is allowedto persist that once an ulcer has perforated there will beno more trouble. For this reason, if for no other, careful

6. Robinson, W. J. Bone Jt Surg. 1935, 17, 267.7. Robinson, W. Amer. J. Surg. 1936, 33, 192.8. Chu, H. J. Proc. Soc. exp. Biol. N.Y. 1938, 38, 99.