480
obviously play a key role. We suggest that prostaglandins (P.G.s) and/or related endoperoxides and thromboxanes are essential for all three processes and that coronary heart-disease can be brought under control by regulating P.G. synthesis and action. O’Brien’ pointed out that most of the drugs which can inhibit platelet aggregation are either inhibitors of P.G. synthesis or P.G. antagonists.2 3 To his list we would add frusemide which can inhibit P.G. synthesis,4 5 adenosine and dipyridamole, which in recent experiments we have shown to be P.G. antagonists, and polyunsaturated fatty acids, which can block P.G. synthesis from arachidonic acid.6 This last observation may explain many of the uncertainties relating to diets rich in unsaturated fatty acids. Such diets are usually rich both in the essential-fatty-acid precursors of P.G. synthesis and in other unsaturated fatty acids which inhibit such synthesis. The precise balance between these will determine whether P.G. synthesis is reduced, increased, or unchanged. In order to inhibit P.G. synthesis polyunsaturated fatty acids without the P..G. precursors should be added to the diet. There is, of course, direct evidence that P.G. endoperoxides and thromboxanes play crucial intermediary roles in platelet aggregation.? 8 P.G.s or related substances may cause coronary vasoconstriction. The membrane-stabilising behaviour which is a key property of many cardiac anti-arrhythmics is probably an indication of P.G. antagonism.23 We have recently shown that in ischsemic perfused animal hearts arrhythmias arising spontaneously or induced by prolactin (whose second messenger is a P.G.) can be blocked by indomethacin whereas those produced by critical p.G.E1 concentrations cannot be so blocked. All three types appear to be blocked by the P.G. antagonist
chloroquine. We therefore suggest that P.G.s and related compounds are the crucial pathogenetic factors in local coronary vasospasm, in platelet aggregation, and in dysrhythmia generation. Control of P.G. synthesis and action should therefore prevent most coronary deaths. We have shown that clinically achievable levels of aspirin-like drugs may produce less than 20% inhibition of P.G. synthesis in blood-vesselslo and thus such drugs alone are unlikely to be effective. We have argued that the pathway of P.G. synthesis and action may be controlled by attacking it at several points.3 We suggest that in addition to an aspirin-like drug, treatment should be supplemented by an intake of polyunsaturated fatty acids free of P.G. precursors and by a P.G. antagonist such as chloroquine with a proven record of low toxicity. Such a regimen might prove more acceptable than many of the apparently relatively ineffective complex programmes of diet and exercise now being promoted. D. F. HORROBIN M. KARMAZYN A. ALLY A. SWIFT M. S. MANKU R. O. MORGAN Clinical Research Institute and University of Montreal, R. A. KARMALI 110 Pine Avenue West, Montreal, Canada
SOCIAL INJUSTICE FOR A SOCIAL WORKER SIR,—The letter trom Mr Mancewicz (Feb. 3, p. :)l4; raises a number of important points. Local authorities in general are inflexible in their insistence that all holders of superannuable posts must join the superan1. O’Brien, J. R. Lancet, 1976, ii, 1307. 2. Manku, M. S., Horrobin, D. F. Prostaglandins, 1976, 12, 789. 3. Manku, M. S., Horrobin, D. F. Lancet, 1976, ii, 1115. 4. Mtabaji, J. P., Manku, M. S., Horrobi n, D. F. Can. J. Physiol. Pharmac. 1976, 54, 357. 5. Ingerman, C. M., Smith, J. B., Silver, M. J. Thromb. Res. 1976, 8, 417. 6. Pace-Asciak, C., Wolfe, L. S. Biochim. biophys. Acta 1968, 152, 784. 7. Malmsten, C., Hamberg, M , Svensson, J., Samuelsson, B. Proc. natn. Acad. Sci. 1975, 72, 1446. 8. Gerrard, J. M., rownsend, D., Stoddard, S., Witkop, C. J., White, J. G. Am. J Path. 1977, 86, 99. 9. Needleman, P., Kulkarni, P. S., Raz, A. Science, 1977, 195, 409. 10. Manku, M. S., Horrobin, D. F. Prostaglandins, 1976, 12, 369.
nuation scheme. The medical adviser is not allowed to recommend that a person is fit for a post, but not fit for superannuation. As the adviser’s primary responsibility is to the employer he is left with no alternative but to reject certain applicants. The only staff who are not covered by the superannuation regulations are temporary staff. In the past it has been possible to recommend that a person be appointed on a temporary basis with a review after a period of time. The applicant is thus given the opportunity to prove himself capable of doing the job and the employing authority is protected if the employee proves to be unfit. It was also possible to recommend extended periods of temporary employment until the medical adviser was satisfied of the employee’s fitness for superannuation. In common with most other medical advisers I have used this device successfully for many years, and it might have been appropriate for Mr Bancewicz’s patient. However, the recent Employment Protection Act has now entered the picture. A person who has been employed for twenty-six weeks is regarded as a permanent employee entitled to all the protection against dismissal afforded by the Act. We are, therefore, limited to a short period of temporary employment-say twenty weeks-to allow time for review before the end of the twenty-six weeks, and this period cannot be extended. Whatever the initial terms of employment it becomes permanent after twenty-six weeks. Such a short period is obviously inadequate in many cases, and if one is unable to say with reasonable certainty that an employee is fit, the only alternative is to reject him. Several times recently a local authority has refused to employ a person for whom I have recommended temporary employment because of the provisions of the Act. I can assure Mr Bancewiz that medical advisers are not unsympathetic to the problems of people who are not one hundred percent fit and in my experience local authorities have a good record in employing such people, but the Law is making life difficult for us at the moment. Westwood
Hospital,
Beverley, N. Humberside
R. SCHOFIELD
SKIN TESTING IN CŒLIAC DISEASE
SIR,-You express surprise (Jan. 15, p. 130) that "until
lately no-one thought of skin testing with the offending agent (gluten or part of it)." This surprise seems unwarranted con-
sidering that the article by Dr Anand and
his colleagues in the issue of The Lancet contains three references to such attempts (the first one in 1957),’ two unsuccessful 1and one showing an occasional response only.3 To these I should like to add two more.4 The surprising fact is the relative success of Baker and Readwho obtained positive skin reactions in 52% of 23 untreated cceliacs with a peptic/tryptic digest of gluten similar to our fraction III7 that had proved unsuccessful in the hands of Housley et a1.2 The 100% success of Dr Anand and his colleagues with a subfraction of fraction III in 10 patients on a gluten-free diet is truly astonishing and must have been due to a high concentration of the antigenic factor by subfractionation on their large stack column. It would be of great interest to know whether antigenicity and clinical toxisame
city run parallel. Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH
R. SCHNEIDER
1. Alvey, C., Anderson, C. M., Freeman, M. Archs Dis. Childh. 1957, 32, 434. 2. Housley, J., Asquith, P., Cooke, W. T. Br. med. J. 1969, ii, 159. 3. Asquith, P. Clins Gastroent. 1974, 3, 213. 4. Collins-Williams, C., Ebbs, J. H. Ann. Allergy, 1954, 12, 237. 5. Breton, A., Vandendorp, F., Dubois, O. Pédiatrie, 1959, 14, 5. 6. Baker, P. G., Read, A. E. Q.Jl Med. 1976, 45, 603. 7. Fraser, A. C., Fletcher, R. F., Ross, C. A. C., Shaw, B., Sammons, H. G., Schneider, R. Lancet, 1959, ii, 252.
obviously play a key role. We suggest that prostaglandins (P.G.s) and/or related endoperoxides and thromboxanes are essential for all three processes and that coronary heart-disease can be brought under control by regulating P.G. synthesis and action. O’Brien’ pointed out that most of the drugs which can inhibit platelet aggregation are either inhibitors of P.G. synthesis or P.G. antagonists.2 3 To his list we would add frusemide which can inhibit P.G. synthesis,4 5 adenosine and dipyridamole, which in recent experiments we have shown to be P.G. antagonists, and polyunsaturated fatty acids, which can block P.G. synthesis from arachidonic acid.6 This last observation may explain many of the uncertainties relating to diets rich in unsaturated fatty acids. Such diets are usually rich both in the essential-fatty-acid precursors of P.G. synthesis and in other unsaturated fatty acids which inhibit such synthesis. The precise balance between these will determine whether P.G. synthesis is reduced, increased, or unchanged. In order to inhibit P.G. synthesis polyunsaturated fatty acids without the P..G. precursors should be added to the diet. There is, of course, direct evidence that P.G. endoperoxides and thromboxanes play crucial intermediary roles in platelet aggregation.? 8 P.G.s or related substances may cause coronary vasoconstriction. The membrane-stabilising behaviour which is a key property of many cardiac anti-arrhythmics is probably an indication of P.G. antagonism.23 We have recently shown that in ischsemic perfused animal hearts arrhythmias arising spontaneously or induced by prolactin (whose second messenger is a P.G.) can be blocked by indomethacin whereas those produced by critical p.G.E1 concentrations cannot be so blocked. All three types appear to be blocked by the P.G. antagonist
chloroquine. We therefore suggest that P.G.s and related compounds are the crucial pathogenetic factors in local coronary vasospasm, in platelet aggregation, and in dysrhythmia generation. Control of P.G. synthesis and action should therefore prevent most coronary deaths. We have shown that clinically achievable levels of aspirin-like drugs may produce less than 20% inhibition of P.G. synthesis in blood-vesselslo and thus such drugs alone are unlikely to be effective. We have argued that the pathway of P.G. synthesis and action may be controlled by attacking it at several points.3 We suggest that in addition to an aspirin-like drug, treatment should be supplemented by an intake of polyunsaturated fatty acids free of P.G. precursors and by a P.G. antagonist such as chloroquine with a proven record of low toxicity. Such a regimen might prove more acceptable than many of the apparently relatively ineffective complex programmes of diet and exercise now being promoted. D. F. HORROBIN M. KARMAZYN A. ALLY A. SWIFT M. S. MANKU R. O. MORGAN Clinical Research Institute and University of Montreal, R. A. KARMALI 110 Pine Avenue West, Montreal, Canada
SOCIAL INJUSTICE FOR A SOCIAL WORKER SIR,—The letter trom Mr Mancewicz (Feb. 3, p. :)l4; raises a number of important points. Local authorities in general are inflexible in their insistence that all holders of superannuable posts must join the superan1. O’Brien, J. R. Lancet, 1976, ii, 1307. 2. Manku, M. S., Horrobin, D. F. Prostaglandins, 1976, 12, 789. 3. Manku, M. S., Horrobin, D. F. Lancet, 1976, ii, 1115. 4. Mtabaji, J. P., Manku, M. S., Horrobi n, D. F. Can. J. Physiol. Pharmac. 1976, 54, 357. 5. Ingerman, C. M., Smith, J. B., Silver, M. J. Thromb. Res. 1976, 8, 417. 6. Pace-Asciak, C., Wolfe, L. S. Biochim. biophys. Acta 1968, 152, 784. 7. Malmsten, C., Hamberg, M , Svensson, J., Samuelsson, B. Proc. natn. Acad. Sci. 1975, 72, 1446. 8. Gerrard, J. M., rownsend, D., Stoddard, S., Witkop, C. J., White, J. G. Am. J Path. 1977, 86, 99. 9. Needleman, P., Kulkarni, P. S., Raz, A. Science, 1977, 195, 409. 10. Manku, M. S., Horrobin, D. F. Prostaglandins, 1976, 12, 369.
nuation scheme. The medical adviser is not allowed to recommend that a person is fit for a post, but not fit for superannuation. As the adviser’s primary responsibility is to the employer he is left with no alternative but to reject certain applicants. The only staff who are not covered by the superannuation regulations are temporary staff. In the past it has been possible to recommend that a person be appointed on a temporary basis with a review after a period of time. The applicant is thus given the opportunity to prove himself capable of doing the job and the employing authority is protected if the employee proves to be unfit. It was also possible to recommend extended periods of temporary employment until the medical adviser was satisfied of the employee’s fitness for superannuation. In common with most other medical advisers I have used this device successfully for many years, and it might have been appropriate for Mr Bancewicz’s patient. However, the recent Employment Protection Act has now entered the picture. A person who has been employed for twenty-six weeks is regarded as a permanent employee entitled to all the protection against dismissal afforded by the Act. We are, therefore, limited to a short period of temporary employment-say twenty weeks-to allow time for review before the end of the twenty-six weeks, and this period cannot be extended. Whatever the initial terms of employment it becomes permanent after twenty-six weeks. Such a short period is obviously inadequate in many cases, and if one is unable to say with reasonable certainty that an employee is fit, the only alternative is to reject him. Several times recently a local authority has refused to employ a person for whom I have recommended temporary employment because of the provisions of the Act. I can assure Mr Bancewiz that medical advisers are not unsympathetic to the problems of people who are not one hundred percent fit and in my experience local authorities have a good record in employing such people, but the Law is making life difficult for us at the moment. Westwood
Hospital,
Beverley, N. Humberside
R. SCHOFIELD
SKIN TESTING IN CŒLIAC DISEASE
SIR,-You express surprise (Jan. 15, p. 130) that "until
lately no-one thought of skin testing with the offending agent (gluten or part of it)." This surprise seems unwarranted con-
sidering that the article by Dr Anand and
his colleagues in the issue of The Lancet contains three references to such attempts (the first one in 1957),’ two unsuccessful 1and one showing an occasional response only.3 To these I should like to add two more.4 The surprising fact is the relative success of Baker and Readwho obtained positive skin reactions in 52% of 23 untreated cceliacs with a peptic/tryptic digest of gluten similar to our fraction III7 that had proved unsuccessful in the hands of Housley et a1.2 The 100% success of Dr Anand and his colleagues with a subfraction of fraction III in 10 patients on a gluten-free diet is truly astonishing and must have been due to a high concentration of the antigenic factor by subfractionation on their large stack column. It would be of great interest to know whether antigenicity and clinical toxisame
city run parallel. Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH
R. SCHNEIDER
1. Alvey, C., Anderson, C. M., Freeman, M. Archs Dis. Childh. 1957, 32, 434. 2. Housley, J., Asquith, P., Cooke, W. T. Br. med. J. 1969, ii, 159. 3. Asquith, P. Clins Gastroent. 1974, 3, 213. 4. Collins-Williams, C., Ebbs, J. H. Ann. Allergy, 1954, 12, 237. 5. Breton, A., Vandendorp, F., Dubois, O. Pédiatrie, 1959, 14, 5. 6. Baker, P. G., Read, A. E. Q.Jl Med. 1976, 45, 603. 7. Fraser, A. C., Fletcher, R. F., Ross, C. A. C., Shaw, B., Sammons, H. G., Schneider, R. Lancet, 1959, ii, 252.
