148 PREVENTION OF POSTOPERATIVE THROMBOEMBOLISM
SIR,-Your editorial (July 12, p. 63) effectively points out the most important factors in a study of thromboembolism: that the observed phenomenon is a true precursor of the final state; and that enough patients are included in a uniform regimen to make the results statistically significant. There is, however, one aspect that should be clarified. You state that Rosengarten and Browse, using the 1251 fibrinogen technique, have shown elastic stockings to be ineffective in reducing the incidence of calf-vein thrombosis, while Wilkins found that elastic compression dramatically reduced the incidence of pulmonary embolism. As you state, one difficulty is the direct equating of calf-vein thrombosis to the incidence of pulmonary embolism. There is, however, an additional difference between the elastic compression studies of Wilkins and those of Rosengarten and Browse. The garment used by the patients studied by Rosengarten and Browse was a single layer of a uniformly elastic tubing of constant diameter. Tests indicate that the elastic tubing used (’Tubigrip’) yields a pressure of about 5 mm Hg at the calf of an average-size leg. The pressure at the ankle is even less, because of the constant-tension constant-diameter characteristics of the elastic tubing. The garment used in the Wilkins study was a knee-high elastic stocking having a graduated compression of approximately 18 mm Hg at the ankle to1 approximately 15 mm Hg at the calf. A recent investigation’ indicates that elastic compression of less than approximately 10 mm Hg at the calf is ineffective in increasing blood velocity or reducing calf pooling. Consequently, the pressures exerted on the calf in the Browse and Rosengarten studies were below physiologically effective levels. Your point that elastic compression, while not totally preventing thrombosis, may inhibit propagation, is well taken. The findings of Flanc et al. indicate that a regimen of elastic compression, leg elevation, exercise, and early ambulation reduced the incidence of deep-vein thrombosis in elderly patients undergoing major operations from 61% to 25%. Flanc et al. also stated that, although the incidence of thrombosis was not reduced in younger patients, the duration of the thrombus as measured by the 1251 fibrinogen test was reduced. This finding would indicate, as you point out, that the prevention of significant thrombus propagation, and not necessarily minithrombus formation itself, may be the mechanism of both anto-coagulant and mechanical prophylaxis. Kendall Research Center, 411 Lake Zurich Road, P.O. Box 476. Barrington, Illinois 60010, U.S.A.
C. R. MEMHARDT
and Privacy seek to replace the Official Secrets Act with a Bill which would allow a patient or his legal representative to refute false reports held against him. In the esoteric world of computers there is a jargon word "gigo", which means "garbage in, garbage out": false or inaccurate data fed into a computer will result in a false and inaccurate solution coming out, The white-paper on computers and privacy stresses human error (accidental or deliberate) as the main danger in the use of modern computer systems. In the United States, where the use of computers has expanded on a grand scale, a Freedom of Information Act operates so successfully in this sensitive area that no special legislation has been found necessary to cover computer usage. Even if all the complex safeguards suggested in the new white-paper and its accompanying repon were faithfully implemented, they would not protect our patients from the greatest danger of all-abuse through the - human element. A Freedom of Information Act would proof the system against abuse, avoid the costly and ineffective measures suggested in the white-paper, and provide a much-needed resurgence of communication between Government and the
people. EDWARD C. HAMLYN
Gainsborough House, 9 Portland
Road,
East Grinstead, Sussex.
CLOTRIMAZOLE AND RHEUMATOID ARTHRITIS to the Ninth Internathe efficacy of the antifungal agent clotrimazole in rheumatoid arthritis prompted us to test the drug in a proven model for detecting anti-inflammatory activity, the rat-paw carrageenan-oedema test.’ We found that clotrimazole exhibits anti-inflammatory activityin the model at doses near those used in Wybum-Mason’s patients (about 100 mg/kg/day). Parallel experiments with aspirin showed the two drugs to be of roughly equivalent potency.
SIR,-Dr R. Wyburn-Mason’s report
tional
Congress of Chemotherapy
(mg/kg) 330 100 33
Because clotrimazole causes adrenal hyperplasia in both rats and dogs,2 we suspected that the anti-inflammatory activity of the drug might derive from acute stimulation of the adrenal We therefore compared the anti-inflammatory effects of domazole in normal and adrenalectomised rats and found that the activity of the drug disappeared after adrenalectomy: % Inhibition of paw swelling
Clotrimazole v.
Phenylbutazone Aspirin
PRIVACY
SIR,-Lord Harris of Greenwich, made the following statement
in the House of Lords
on
Nov. 25: "The Government
are
pressing ahead with the preparation of detailed proposals to meet our broad Manifesto commitment to ’replace the Offi...
cial Secrets Acts by a measure to put the burden on the public authorities to justify witholding information’." The medical profession should seize on this promise and renew efforts to persuade Parliament to provide patients with urgently needed safeguards. Patients require protection from the misuse of medical records by Government Departments. Mr Andrew Bowden, M.P., writing3 on computerised medical records, stated that errors of information are difficult to correct and could gravely damage an individual. The House of Commons All-Party Committee on Freedom of Information
3. Pulse, Nov. 22, 1975.
R. Archs. Sur.
Oral dose
Normal
(mg/ kg)
rats
330 33 330
Expt4355 56
1
Adrenalectomaed rats
2
1
Expt 46 Expt613 Expt1 55
2
57
..
46
..
Aspirin and phenylbutazone, classical anti-inflammatory drugs which may act by inhibiting the synthesis of prostaglandin mediators of inflammation,3do not depend on adrenal function for activity in the rat model and were included in out experiments as reference standards. Dr Wyburn-Mason seems to believe that rheumatoid art!! ritis is provoked by protozoa which are susceptible to clotnmazole. Our data suggests an alternative, and not attractiva pharmacological basis for the apparent clinical anti-inflawt tory effect of the drug. Department of Pharmacology, Central Research Division, Pfizer Inc., Groton, Connecticut 06340, U.S.A.
IVAN G. OTTERNESS JOHN F. NIBLACK
Winter, C. A., Risely, E. A., Nuss, G. W. Proc. Soc. exp. Biol. Med. 1962, 111, 544. 2. Tettenborn, D. Postgrad. med. J. 1974, 50, suppl. i, p. 17. 3. Flower, R. J., Gryglewski, R., Herbaczynska-Cedro, K., Vane, J. R., Nature new Biol. 1972, 238, 104. 1.
Sigel, B. Edelstein, A. L., Savitch, L., Hasty, J. H., Felix, 1975, 10, 171. 2. Flanc C., Kakkar, V. V., Clarke, M. B. Lancet, 1969, i, 477. 1.
on
% inhibition of paw swelling Clotrimazole Aspirin 44 58 29 36 2 17
Oral dose
Drug
SECRECY
on
Medical Adviser to the House of Commons All-Party Committee Freedom of Information and Privacy
SIR,-Your editorial (July 12, p. 63) effectively points out the most important factors in a study of thromboembolism: that the observed phenomenon is a true precursor of the final state; and that enough patients are included in a uniform regimen to make the results statistically significant. There is, however, one aspect that should be clarified. You state that Rosengarten and Browse, using the 1251 fibrinogen technique, have shown elastic stockings to be ineffective in reducing the incidence of calf-vein thrombosis, while Wilkins found that elastic compression dramatically reduced the incidence of pulmonary embolism. As you state, one difficulty is the direct equating of calf-vein thrombosis to the incidence of pulmonary embolism. There is, however, an additional difference between the elastic compression studies of Wilkins and those of Rosengarten and Browse. The garment used by the patients studied by Rosengarten and Browse was a single layer of a uniformly elastic tubing of constant diameter. Tests indicate that the elastic tubing used (’Tubigrip’) yields a pressure of about 5 mm Hg at the calf of an average-size leg. The pressure at the ankle is even less, because of the constant-tension constant-diameter characteristics of the elastic tubing. The garment used in the Wilkins study was a knee-high elastic stocking having a graduated compression of approximately 18 mm Hg at the ankle to1 approximately 15 mm Hg at the calf. A recent investigation’ indicates that elastic compression of less than approximately 10 mm Hg at the calf is ineffective in increasing blood velocity or reducing calf pooling. Consequently, the pressures exerted on the calf in the Browse and Rosengarten studies were below physiologically effective levels. Your point that elastic compression, while not totally preventing thrombosis, may inhibit propagation, is well taken. The findings of Flanc et al. indicate that a regimen of elastic compression, leg elevation, exercise, and early ambulation reduced the incidence of deep-vein thrombosis in elderly patients undergoing major operations from 61% to 25%. Flanc et al. also stated that, although the incidence of thrombosis was not reduced in younger patients, the duration of the thrombus as measured by the 1251 fibrinogen test was reduced. This finding would indicate, as you point out, that the prevention of significant thrombus propagation, and not necessarily minithrombus formation itself, may be the mechanism of both anto-coagulant and mechanical prophylaxis. Kendall Research Center, 411 Lake Zurich Road, P.O. Box 476. Barrington, Illinois 60010, U.S.A.
C. R. MEMHARDT
and Privacy seek to replace the Official Secrets Act with a Bill which would allow a patient or his legal representative to refute false reports held against him. In the esoteric world of computers there is a jargon word "gigo", which means "garbage in, garbage out": false or inaccurate data fed into a computer will result in a false and inaccurate solution coming out, The white-paper on computers and privacy stresses human error (accidental or deliberate) as the main danger in the use of modern computer systems. In the United States, where the use of computers has expanded on a grand scale, a Freedom of Information Act operates so successfully in this sensitive area that no special legislation has been found necessary to cover computer usage. Even if all the complex safeguards suggested in the new white-paper and its accompanying repon were faithfully implemented, they would not protect our patients from the greatest danger of all-abuse through the - human element. A Freedom of Information Act would proof the system against abuse, avoid the costly and ineffective measures suggested in the white-paper, and provide a much-needed resurgence of communication between Government and the
people. EDWARD C. HAMLYN
Gainsborough House, 9 Portland
Road,
East Grinstead, Sussex.
CLOTRIMAZOLE AND RHEUMATOID ARTHRITIS to the Ninth Internathe efficacy of the antifungal agent clotrimazole in rheumatoid arthritis prompted us to test the drug in a proven model for detecting anti-inflammatory activity, the rat-paw carrageenan-oedema test.’ We found that clotrimazole exhibits anti-inflammatory activityin the model at doses near those used in Wybum-Mason’s patients (about 100 mg/kg/day). Parallel experiments with aspirin showed the two drugs to be of roughly equivalent potency.
SIR,-Dr R. Wyburn-Mason’s report
tional
Congress of Chemotherapy
(mg/kg) 330 100 33
Because clotrimazole causes adrenal hyperplasia in both rats and dogs,2 we suspected that the anti-inflammatory activity of the drug might derive from acute stimulation of the adrenal We therefore compared the anti-inflammatory effects of domazole in normal and adrenalectomised rats and found that the activity of the drug disappeared after adrenalectomy: % Inhibition of paw swelling
Clotrimazole v.
Phenylbutazone Aspirin
PRIVACY
SIR,-Lord Harris of Greenwich, made the following statement
in the House of Lords
on
Nov. 25: "The Government
are
pressing ahead with the preparation of detailed proposals to meet our broad Manifesto commitment to ’replace the Offi...
cial Secrets Acts by a measure to put the burden on the public authorities to justify witholding information’." The medical profession should seize on this promise and renew efforts to persuade Parliament to provide patients with urgently needed safeguards. Patients require protection from the misuse of medical records by Government Departments. Mr Andrew Bowden, M.P., writing3 on computerised medical records, stated that errors of information are difficult to correct and could gravely damage an individual. The House of Commons All-Party Committee on Freedom of Information
3. Pulse, Nov. 22, 1975.
R. Archs. Sur.
Oral dose
Normal
(mg/ kg)
rats
330 33 330
Expt4355 56
1
Adrenalectomaed rats
2
1
Expt 46 Expt613 Expt1 55
2
57
..
46
..
Aspirin and phenylbutazone, classical anti-inflammatory drugs which may act by inhibiting the synthesis of prostaglandin mediators of inflammation,3do not depend on adrenal function for activity in the rat model and were included in out experiments as reference standards. Dr Wyburn-Mason seems to believe that rheumatoid art!! ritis is provoked by protozoa which are susceptible to clotnmazole. Our data suggests an alternative, and not attractiva pharmacological basis for the apparent clinical anti-inflawt tory effect of the drug. Department of Pharmacology, Central Research Division, Pfizer Inc., Groton, Connecticut 06340, U.S.A.
IVAN G. OTTERNESS JOHN F. NIBLACK
Winter, C. A., Risely, E. A., Nuss, G. W. Proc. Soc. exp. Biol. Med. 1962, 111, 544. 2. Tettenborn, D. Postgrad. med. J. 1974, 50, suppl. i, p. 17. 3. Flower, R. J., Gryglewski, R., Herbaczynska-Cedro, K., Vane, J. R., Nature new Biol. 1972, 238, 104. 1.
Sigel, B. Edelstein, A. L., Savitch, L., Hasty, J. H., Felix, 1975, 10, 171. 2. Flanc C., Kakkar, V. V., Clarke, M. B. Lancet, 1969, i, 477. 1.
on
% inhibition of paw swelling Clotrimazole Aspirin 44 58 29 36 2 17
Oral dose
Drug
SECRECY
on
Medical Adviser to the House of Commons All-Party Committee Freedom of Information and Privacy
