576
(who had never taken garlic and onion) have significantly higher serum-triglycerides, beta lipoproteins, phospholipids, and plasma-fibrinogen levels. Serum-cholesterol levels were apparently higher in group n, but there was no sig(4.) Group
ii
nificant difference from other groups. We conclude that regular consumption of onion and garlic in diet has a protective effect on some important factors which influence atherosclerosis. G. S. SAINANI D. B. DESAI K. N. MORE
Departments of Medicine and Biochemistry, B. J. Medical College & Sassoon General Hospitals Poona-1, India
FAILURE OF ASPIRIN TO REVERSE INTESTINAL SECRETION AFTER CHOLERA TOXIN IN DOGS
SIR,-Aspirin blocks cholera toxin if given before, with, or just after toxin, and has been recommended for clinical trials.’2 Pretreatment with activated charcoal, cholera antitoxin, kaolin, or ganglioside blocks cholera toxin, but does not reverse diarrhoea previously induced by toxin.3 Ethacrynic acid3 and cycloheximide6 reduce secretion when given after cholera toxin, but net absorption results only from sugars or aminoacids which enhance sodium and
water
absorption.7-9 A
potential anti-cholera drug should safely reverse toxin-induced fluid accumulation when given after fluid accumulation has
begun. Before conducting clinical trials of drugs the following procedure is suggested.
new
anti-cholera
SALICYLATES AND RESPONSE TO CHOLERA
hourly for 2 or3 fluid accumulation was measured using 100 mmol/1 NaCI with phenolsulfonpthalein (37°C). Net water Loop fluid
was
hours. Then
withdrawn and measured
net
fluxes were calculated from changes in P.s.p. concentration in 16 loops of 8 dogs (see accompanying table).lo Then sodium salicylate or acetylsalicylic acid was injected intravenously. In some dogs salicylate was also given intraluminally. Acetylsalicylic acid was dissolved just before injection with the least 10% NaOH required (3 or 6 ml). Fluid accumulation rate was measured at 3 and 5 hours. Before toxin net absorption is in-
variably present.’" Sodium salicylate and aspirin given after secretion had begun had no effect on cholera-induced fluid accumulation. All dogs developed salicylate intoxication with vomiting, hyperventilation (mean 67/min.), and respiratory alkalosis (mean change in blood pH from 7.357 to 7.471 and mean fall in bicarbonate of 3 mmol/1). Other values remained normal, but temperatures rose 2°C. Salicylates resemble other compounds which prevent the action of cholera toxin but cannot reverse its action. Salicylates in high dosesl2 are toxic and could fatally complicate the metabolic acidosis of cholera. Since standard cholera therapy is almost 100% effective" and tetracycline prophylaxis is available,12 a clinical trial of salicylates in cholera is unwarranted, Evaluation of drugs for antagonism to enterotoxins should always include tests conducted after toxin-induced secretion has begun. International Centre for Medical Research, 550 North Broadway, Suite 115, Baltimore, Maryland 21205, U.S.A.
DAVID R. NALIN
CULTIVATION OF VIRAL AGENTS FROM CROHN’S DISEASE
Dogs 1-3 received sodium salicylate; dogs 4-8 received aspirin. Fluxes were measured at 3 hours (dogs 1-3) or 2 hours after toxin (dogs 4-8). Times in parentheses refer to interval after salicylate administration. Fluxes for dogs 5-8 are given as mean is.D. p=proximal loops (12), D=distal loops (12). There are no significant differences between net water fluxes before and after salicylate administration. (+)=Net absorption, (-)=Net secretion.
Adult dogs (10-17 kg) were lightly anaesthetised with sodium pentobarbitone, and fluid losses were matched with intravenous normal saline. Two ligated cannulated 20 cm jejunal loops were created,1O replaced intraperitoneally, and rinsed (normal saline,37°C). Pulse, temperature, respiratory rate, serum-sodium, plasma specific gravity, arterial blood pH and venous bicarbonate were measured by standard methods before and after the studies. 10 ml of freshly reconstituted N.I.H. lot no. 001or 0-15 ml of lot 002 cholera toxin (2-5g/dl) in 10 ml of normal saline were injected intraluminally and rinsed out after 10 minutes. 1. Jacoby, H. I., Marshall, C. H. Nature, 1972, 235, 163. 2. Fink, A. D., Katz, R. L. ibid. 1972, 238, 273. 3. Nalin, D. R., Cash, R. A. J. Pak. med. Ass. 1970, 20, 177. 4. van Heyningen, Carpenter, C. C. J., Pierce, N. F., Greenough, W. B. J. infect. Dis. 1971, 124, 415. 5. Carpenter, C. C. J., Curlin, G. T., Greenough, W. B. ibid. 1969, 120, 332. 6. Harper, D. T. Jr., Yardley, J. H., Hendrix, T. R. Johns Hopk. med. J. 1970,
126, 258. Phillips, R. A. Fedn. Proc. 1964, 23, 705. Hirschhorn, N., Kinzie, J. L., Sachar, D. B., Northrup, R. S., Taylor, J. O., Adhmad, S. Z., Phillips, R. A. New Engl. J. Med. 1968, 279, 176. 9. Nalin, D. R., Cash, R. A., Rahaman, M., Yunus, M. Gut, 1970, 11, 768. 10. Nalin, D. R., Ally, K., Hare, K., Hare, R. J. infect. Dis. 1972, 125, 528. 7. 8.
SIR,-We read with interest the articles by Dr Gitnick and his colleagues (July 31) but we object to the first sentence in the summary of the first one (p. 215) that reads: "The isolation and animal transmission of a viral agent from Crohn’s disease patients ..." This suggests that a viral agent has been isolated from Crohn’s disease and that this agent has been shown to transmit the disease to laboratory animals. A more accurate statement would be that the work by Cave et ale supports a viral aetiology for Crohn’s disease."While Cave et al. demonstrated that the transmissible agent could pass through a 0.2 2 tm filter, they did not show that this agent was a virus, We have detected aberrant Pseudomonas bacteria which can pass through a 0.2 m filter.’ Our report concerns itself with the cultivation of these aberrant bacteria from the filtrate obtained by passage of Crohn’s disease tissue homogenates through a 0.22 .m filter. Cave’s experiments, therefore, do not necessarily prove that the transmissible agent in Crohn’s disease is a virus. The reports by Dr Gitnick and his colleagues are intriguing. and they are to be congratulated on the excellence of their work. Their findings and ours are not mutually exclusive, for the viral agents which they describe could induce the aberrant bacteria we found. We do not know which agent or agents are necessary for the induction of Crohn’s disease, but these developments are very exciting. Section of Gastroenterology, Marshfield Clinic, Marshfield, Wisconsin 54449,
U.S.A.
KEVIN PARENT PAUL MITCHELL
11. Nalin, D. R. Trop. geogr. Med. 1972, 24, 101. 12. McCormack, W. M., Chowdhury, A. M., Jahanigir, N., Ahmed, A. B. F Mosley, W. H. Bull. Wld Hlth Org. 1968, 38, 787. 13. Cave, D. R., Mitchell, M. D., Brooke, B. N. Gastroenterology, 1975, 69, 618. 14. Parent, K., Mitchell, P. D. ibid. 1976, 71, 365.
(who had never taken garlic and onion) have significantly higher serum-triglycerides, beta lipoproteins, phospholipids, and plasma-fibrinogen levels. Serum-cholesterol levels were apparently higher in group n, but there was no sig(4.) Group
ii
nificant difference from other groups. We conclude that regular consumption of onion and garlic in diet has a protective effect on some important factors which influence atherosclerosis. G. S. SAINANI D. B. DESAI K. N. MORE
Departments of Medicine and Biochemistry, B. J. Medical College & Sassoon General Hospitals Poona-1, India
FAILURE OF ASPIRIN TO REVERSE INTESTINAL SECRETION AFTER CHOLERA TOXIN IN DOGS
SIR,-Aspirin blocks cholera toxin if given before, with, or just after toxin, and has been recommended for clinical trials.’2 Pretreatment with activated charcoal, cholera antitoxin, kaolin, or ganglioside blocks cholera toxin, but does not reverse diarrhoea previously induced by toxin.3 Ethacrynic acid3 and cycloheximide6 reduce secretion when given after cholera toxin, but net absorption results only from sugars or aminoacids which enhance sodium and
water
absorption.7-9 A
potential anti-cholera drug should safely reverse toxin-induced fluid accumulation when given after fluid accumulation has
begun. Before conducting clinical trials of drugs the following procedure is suggested.
new
anti-cholera
SALICYLATES AND RESPONSE TO CHOLERA
hourly for 2 or3 fluid accumulation was measured using 100 mmol/1 NaCI with phenolsulfonpthalein (37°C). Net water Loop fluid
was
hours. Then
withdrawn and measured
net
fluxes were calculated from changes in P.s.p. concentration in 16 loops of 8 dogs (see accompanying table).lo Then sodium salicylate or acetylsalicylic acid was injected intravenously. In some dogs salicylate was also given intraluminally. Acetylsalicylic acid was dissolved just before injection with the least 10% NaOH required (3 or 6 ml). Fluid accumulation rate was measured at 3 and 5 hours. Before toxin net absorption is in-
variably present.’" Sodium salicylate and aspirin given after secretion had begun had no effect on cholera-induced fluid accumulation. All dogs developed salicylate intoxication with vomiting, hyperventilation (mean 67/min.), and respiratory alkalosis (mean change in blood pH from 7.357 to 7.471 and mean fall in bicarbonate of 3 mmol/1). Other values remained normal, but temperatures rose 2°C. Salicylates resemble other compounds which prevent the action of cholera toxin but cannot reverse its action. Salicylates in high dosesl2 are toxic and could fatally complicate the metabolic acidosis of cholera. Since standard cholera therapy is almost 100% effective" and tetracycline prophylaxis is available,12 a clinical trial of salicylates in cholera is unwarranted, Evaluation of drugs for antagonism to enterotoxins should always include tests conducted after toxin-induced secretion has begun. International Centre for Medical Research, 550 North Broadway, Suite 115, Baltimore, Maryland 21205, U.S.A.
DAVID R. NALIN
CULTIVATION OF VIRAL AGENTS FROM CROHN’S DISEASE
Dogs 1-3 received sodium salicylate; dogs 4-8 received aspirin. Fluxes were measured at 3 hours (dogs 1-3) or 2 hours after toxin (dogs 4-8). Times in parentheses refer to interval after salicylate administration. Fluxes for dogs 5-8 are given as mean is.D. p=proximal loops (12), D=distal loops (12). There are no significant differences between net water fluxes before and after salicylate administration. (+)=Net absorption, (-)=Net secretion.
Adult dogs (10-17 kg) were lightly anaesthetised with sodium pentobarbitone, and fluid losses were matched with intravenous normal saline. Two ligated cannulated 20 cm jejunal loops were created,1O replaced intraperitoneally, and rinsed (normal saline,37°C). Pulse, temperature, respiratory rate, serum-sodium, plasma specific gravity, arterial blood pH and venous bicarbonate were measured by standard methods before and after the studies. 10 ml of freshly reconstituted N.I.H. lot no. 001or 0-15 ml of lot 002 cholera toxin (2-5g/dl) in 10 ml of normal saline were injected intraluminally and rinsed out after 10 minutes. 1. Jacoby, H. I., Marshall, C. H. Nature, 1972, 235, 163. 2. Fink, A. D., Katz, R. L. ibid. 1972, 238, 273. 3. Nalin, D. R., Cash, R. A. J. Pak. med. Ass. 1970, 20, 177. 4. van Heyningen, Carpenter, C. C. J., Pierce, N. F., Greenough, W. B. J. infect. Dis. 1971, 124, 415. 5. Carpenter, C. C. J., Curlin, G. T., Greenough, W. B. ibid. 1969, 120, 332. 6. Harper, D. T. Jr., Yardley, J. H., Hendrix, T. R. Johns Hopk. med. J. 1970,
126, 258. Phillips, R. A. Fedn. Proc. 1964, 23, 705. Hirschhorn, N., Kinzie, J. L., Sachar, D. B., Northrup, R. S., Taylor, J. O., Adhmad, S. Z., Phillips, R. A. New Engl. J. Med. 1968, 279, 176. 9. Nalin, D. R., Cash, R. A., Rahaman, M., Yunus, M. Gut, 1970, 11, 768. 10. Nalin, D. R., Ally, K., Hare, K., Hare, R. J. infect. Dis. 1972, 125, 528. 7. 8.
SIR,-We read with interest the articles by Dr Gitnick and his colleagues (July 31) but we object to the first sentence in the summary of the first one (p. 215) that reads: "The isolation and animal transmission of a viral agent from Crohn’s disease patients ..." This suggests that a viral agent has been isolated from Crohn’s disease and that this agent has been shown to transmit the disease to laboratory animals. A more accurate statement would be that the work by Cave et ale supports a viral aetiology for Crohn’s disease."While Cave et al. demonstrated that the transmissible agent could pass through a 0.2 2 tm filter, they did not show that this agent was a virus, We have detected aberrant Pseudomonas bacteria which can pass through a 0.2 m filter.’ Our report concerns itself with the cultivation of these aberrant bacteria from the filtrate obtained by passage of Crohn’s disease tissue homogenates through a 0.22 .m filter. Cave’s experiments, therefore, do not necessarily prove that the transmissible agent in Crohn’s disease is a virus. The reports by Dr Gitnick and his colleagues are intriguing. and they are to be congratulated on the excellence of their work. Their findings and ours are not mutually exclusive, for the viral agents which they describe could induce the aberrant bacteria we found. We do not know which agent or agents are necessary for the induction of Crohn’s disease, but these developments are very exciting. Section of Gastroenterology, Marshfield Clinic, Marshfield, Wisconsin 54449,
U.S.A.
KEVIN PARENT PAUL MITCHELL
11. Nalin, D. R. Trop. geogr. Med. 1972, 24, 101. 12. McCormack, W. M., Chowdhury, A. M., Jahanigir, N., Ahmed, A. B. F Mosley, W. H. Bull. Wld Hlth Org. 1968, 38, 787. 13. Cave, D. R., Mitchell, M. D., Brooke, B. N. Gastroenterology, 1975, 69, 618. 14. Parent, K., Mitchell, P. D. ibid. 1976, 71, 365.
