278 In the disc sensitivity test, 25 µg. discs of colistin sulphate have been shown to produce zones of inhibition with organisms that have minimum inhibitory concentrations in the range usually obtained after the recommended intramuscular dose of 2,000,000 units of C.S.M.S. every 8 hours. The larger 100 µg. discs should be used for testing organisms in urinary infections, since urine normally contains a higher level of colomycin than blood (200400 gg. per ml.). They can also be used to test organisms that are resistant to inhibition by the 25 µg. discs with a view to increasing the dose of colomycin administered if they prove sensitive.
the agricultural community, both official and commercial, whilst concerned about its toxicity, nevertheless consider it
We do not provide instructions as to inoculum size, 3 a survey carried out in 1970, Castle and Elstub found that a variety of different methods of spreading the inoculum were used and there was little evidence of any correlation between the type of inoculum, method of spreading, and the resulting growth. We would, however, be happy to provide information on these points if required. Serum levels of colomycin are reported to average 10-14 g. per ml. after 2,000,000 units and > 25 µg. per ml. after 3,000,000 units intramuscularly. However, these levels do vary widely. Polymyxins act synergistically with the natural bactericidal systems against Escherichia, but are adversely affected, possibly by the calcium present in
CONTRIBUTIONS TO THE LANCET SIR,--In your issue of Jan. 4 (p. 54) I noted the " analysis " under the above title, and reflected upon the purpose of this revelation. To summarise, you reject five out of six signed articles submitted, contributions emanate from sixty countries around the world, and some 5% derive from developing countries. All, no doubt, interesting figures; but without further information the figures are virtually meaningless. The rejection-rate may indicate that five out of six articles are of poor quality, of inappropriate content for The Lancet, limitations of space, &c., &c. The second point of geographic origins of contributions is likewise on first sight impressive and indicative of world-wide respect which The Lancet engenders. Certainly 50% of contributions originating from outside the U.K. is notable, but again this proportion could reflect a deliberate bias on the part of the editor(s). It may be that you have predetermined as a deliberate policy, for example, that only 50% of contributions should be from within the U.K. and that (to promote sales for example) you reserve 20% of space for U.S.A. contributions. The third point-that some 4-5% of contributions derive from underdeveloped territories-is interesting, but what proportion of those 566 that achieved publication were from developing countries ? Taking as acknowledged that The Lancet has international status over and above many local journals in developing countries, I raise the issue as to whether it is in the interests of the local journals that you should publish such articles. Is it not derogatory to the improvement of the standards and circulation of such journals ? Are the articles of more worldwide significance than of local interest ? On what basis do you make your selection ? -The issue cannot be avoided by replying that you are not responsible for the submissions (and I admit to personal guilt!). It is a serious point as to whether you should encourage overseas authors by accepting the cream of articles, or whether you should support the development of local journals by referring back all articles for first refusal by the local journal. The criteria for acceptance are critical. The essence of this letter is to point out that the mere publication of such figures without an accompanying" explanation (is there a distinction between " signed articles and " signed contributions " ?) of editorial policy and intent is somewhat valueless-though perhaps ego-inflating on first sight. And to stimulate you into publishing a clear statement-or have I missed the relevant editorial ?
since, in
serum, in their action
against Pseudomonas.4
Pharmax Medical Limited, Bourne Road, Bexley, Kent DA5 1NX.
SUSAN F. SULLMAN, Head of Technical Services Department.
PRIAPISM DURING REGULAR DIALYSIS SIR,--The correspondence following the paper by Dr Port and others (Nov. 30, p. 1287) describes the difficulties of treatment of this condition, particularly when Peyronie’s disease has developed. The most heroic treatment, including surgery, seems to be of little value. May I draw attention to the paper by Heslop et al.5, describing the value of ultrasonic therapy in these cases, which the authors describe as having " material advantages over radiotherapy, surgery, steroid therapy, or other drug administration " ? Manchester Victoria Memorial
Jewish Hospital, Cheetham, Manchester M8 8TT.
BERNARD SANDLER.
PARAQUAT SIR,—The letter of Dr Binnie (Jan. 18, p. 169) about paraquat requires some comment. Inquiry of the Regional Poisons Centres does not confirm his quoted figures. In the United Kingdom in 1974 there were 34 deaths due to paraquat, of which 21 were suicides, 7 of unknown circumstances, and 2 homicidal. The deaths were not concentrated in any particular area as Dr Binnie’s figures might suggest. A recent review of paraquat poisoning6 showed that, at the time of writing, of 97 cases recorded in the medical literature 29 recovered, and our own records of other cases confirm this proportion. It is to be hoped that the recently suggested treatmentwill improve these figures. The ethical justification for the continued use of paraquat must be in its great value in helping food production. Due to its unique properties it is at present irreplaceable by other herbicides in most applications. In well over 100 countries 3. 4.
Castle, A. R., Elstub, J. J. clin. Path. 1971, 24, 773. Davis, S. D., Iannetta, A., Wedgwood, R. O. J. infect. Dis. 1971, 123, 392.
5. Heslop, R. W., Oakland, D. J., Maddox, B. T. Br. J. Urol. 1967, 39. 6. Fletcher, K., in Forensic Toxicology (edited by B. Ballantyne); p. 86. Bristol, 1974. 7. Smith, L. L., Wright, A., Wyatt, I., Rose, M. S. Br. med. J. 1974, iv, 569.
indispensable. Imperial Chemical Industries Limited, Alderley Park, near Macclesfield, Cheshire SK10 4TJ.
K. FLETCHER.
Department of Tropical Community Health,
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA.
REX FENDALL.
**Our note was deliberately terse: good readers, like good eaters, are usually concerned more with the fare that is placed before them than with the source of the ingredients that
included or excluded. But this short note its like (3 column-inches), predecessors covering the years from 1966 onwards, may have had some slight value in providing evidence and solace to disappointed authors who had been notified in the previous twelve months that their were
279 be declined for lack of space. The to those fascinated by the capacity for rapid international communication which has evolved in the past thirty years. The Lancet has no bias towards or against contributions (i.e., articles and Letters to the Editor) from any one continent or any one country; and no-one in Adam Street has the faintest notion of how the latest annual return will differ from the previous year’s until the calculations have been feverishly completed at the end of December. Professor Fendall’s third point-the interests of local journals-does not concern only developing countries: it was being debated three decades ago in developed regions (including Australasia and Scandinavia) which have local journals. Such journals, it then seemed, became reconciled to losing many articles that were of more than local interest to U.S. or U.K. journals with a wider circulation. It is difficult to see how otherwise the information in these articles can be surely and quickly disseminated; even the most determined reader cannot hope to scan all local journals. Last week (p. 210) The Lancet published an article on experience with a mortality committee in a hospital in Kenya. The author concluded that the approach he described might prove helpful in most hospitals in developing countries. Professor Fendall would evidently have had us suggest to the author that he publish his findings in East Africa. The author might well have decided against adopting this suggestion; and, if so, he would, we believe, have been right.-ED. L.
contributions
note may
also
must
appeal
ORAL BACTERIAL VACCINE AND COLDS Sn:,—In a similar manner to that of Dr Tyrrell (Jan. 11, p. 108), our trialwas conducted on strict double-blind lines. There was no difference in the frequency and duration of colds in the two groups, whereas the severity as judged by the number of days absent showed a statistically significant reduction in the vaccine group. Our methods of recording, 1972-73, differed in that the school boarders were throughout the trial period observed by the matron and medical staff. Our experience has shown that the method of retrospective subjective impressions of colds taken at the end of a trial usually is of little value compared with the method of parallel current study. We have found a similar result with this vaccine in patients with chronic bronchitis in the older age-groups. The reduction in the number of days absent in the vaccine group was of the same order from 10-17 years, suggesting that natural acquired immunity did not occur. In their report2 Tyrrell et al. mention the work of Tomasi et awl. on the IgA local secretory antibody system. Further study’along these lines is indicated by our results. Western Hospital, London SW6.
H. C. PRICE.
Bristol.
G. HENLEY.
HETEROZYGOTE ADVANTAGE IN CYSTIC FIBROSIS SiR,—Commenting on the recent correspondence (Jan. 18, p. 167) on the as yet unidentified biological advantage that theory demands the cystic-fibrosis heterozygote to possess, would it be too fanciful to suggest that this could lie in an exceptional agreeableness of these individuals ? Such a quality has in my experience been a striking feature of the personalities of mothers of children with cystic fibrosis. Since (until perhaps recent years) 1. Price, M. C., Henley, G. Practitioner, 1974, 213, 720. 2. Tyrrell, D. A. J., Nolan, P. S., Reed, S. E., Healey, M. J. R. Br. J. prev. soc. Med. 1972, 26, 129. 3. Tomasi, T. B., Tan, E., Solomon, A., Prendergast, R. A. J. exp. Med. 1965, 131, 101.
populations have had an excess of females over males of marriageable age, exceptionally agreeable females would presumably carry a reproductive advantage. Department of Pædiatrics, Addenbrooke’s Hospital, Cambridge CB2 2QQ.
DOUGLAS GAIRDNER.
KANAM MANDIBLE’S TUMOUR SiR,-Since suggested diagnoses often become firmly entrenched in medical folk lore, I feel that Dr Stathopoulos’s suggestion (Jan. 18, p. 165) that the Kanam mandible may have been the seat of Burkitt’s lymphoma should be closely examined. " The interpretation of archaic pathology is often a task of extreme complexity " and " in palaeopathology the best opinions are often tentative opinions ".1 The changes in the Kanam mandible (interpreted by Tobias as a subperiosteal ossifying sarcoma) have been by Brothwell as a malignant tumour in which accepted " osteosarcomafit’ the macroscopic picture well although there is some difference of opinion on this diagnosis ".2 Goldstein believes the lesion to be a " sarcomatous overgrowth ".3Wells, however, states that the Kanam mandible has been " diagnosed as a sarcoma but its present status is doubtful ".4 I have also expressed reservations.5I) I feel that the changes might have resulted from any process elevating the periosteum and it is interesting to note that Brothwell, before opting for osteosarcoma, considered the possibility of trauma and low-grade inflammation with much subperiosteal new bone. I would suggest, therefore, that it is premature to consider too seriously the question of Burkitt’s lymphoma in this mid-Pleistocene fossil. It is by no means proven that the changes are even neoplastic. -
University Pathology Department, Western Infirmary, Glasgow G11 6NT.
A. T. SANDISON.
INTESTINAL ABSORPTION OF GLUCOSE SiR,—We were impressed by the work of Dr Read and others (Sept. 14, p. 624) in measuring the kinetics of glucose absorption by means of transmural electrical potentials in the jejunum. We were further gratified by the attention they devoted to our own studies, but we should like to respond to two of the issues they raised during a comparison of results. First, our use of prolonged infusion periods and of transintestinal intubation were not, as Read et al. said, necessitated by instability of the measured potential differences (P.D.S). In fact, our P.D.S were invariably stable within 15 minutes of each infusion. Using constant infusion-rates, we did not observe any motility-induced fluctuations of P.D., and the effects of any transient fluctuations (as well as of A.c. interference) were eliminated simply by attaching a 0-1 .F capacitor across the input poles of our potentiometer, without our having to resort to pharmacological manipulations such as propantheline. Our use of prolonged infusion periods and of transintestinal intubation were dictated rather by other aspects of experimental design, since we were simultaneously carrying out many additional measurements (reported separately) of net glucose, water, and electrolyte fluxes over multiple Wells, C. in Diseases in Antiquity (edited by D. Brothwell and A. T. Sandison); p. 5. Springfield, Illinois, 1967. 2. Brothwell, D. ibid. p. 330. 3. Goldstein, M. S. in Science in Archæology (edited by D. Brothwell and E. Higgs); p. 485. London, 1969. 4. Wells, C. Bones, Bodies and Disease; p. 75. London, 1964. 5. Sandison, A. T. in The Skeletal Biology of Earlier Human Populations (edited by D. Brothwell); p. 230. Oxford, 1968. 1.
the agricultural community, both official and commercial, whilst concerned about its toxicity, nevertheless consider it
We do not provide instructions as to inoculum size, 3 a survey carried out in 1970, Castle and Elstub found that a variety of different methods of spreading the inoculum were used and there was little evidence of any correlation between the type of inoculum, method of spreading, and the resulting growth. We would, however, be happy to provide information on these points if required. Serum levels of colomycin are reported to average 10-14 g. per ml. after 2,000,000 units and > 25 µg. per ml. after 3,000,000 units intramuscularly. However, these levels do vary widely. Polymyxins act synergistically with the natural bactericidal systems against Escherichia, but are adversely affected, possibly by the calcium present in
CONTRIBUTIONS TO THE LANCET SIR,--In your issue of Jan. 4 (p. 54) I noted the " analysis " under the above title, and reflected upon the purpose of this revelation. To summarise, you reject five out of six signed articles submitted, contributions emanate from sixty countries around the world, and some 5% derive from developing countries. All, no doubt, interesting figures; but without further information the figures are virtually meaningless. The rejection-rate may indicate that five out of six articles are of poor quality, of inappropriate content for The Lancet, limitations of space, &c., &c. The second point of geographic origins of contributions is likewise on first sight impressive and indicative of world-wide respect which The Lancet engenders. Certainly 50% of contributions originating from outside the U.K. is notable, but again this proportion could reflect a deliberate bias on the part of the editor(s). It may be that you have predetermined as a deliberate policy, for example, that only 50% of contributions should be from within the U.K. and that (to promote sales for example) you reserve 20% of space for U.S.A. contributions. The third point-that some 4-5% of contributions derive from underdeveloped territories-is interesting, but what proportion of those 566 that achieved publication were from developing countries ? Taking as acknowledged that The Lancet has international status over and above many local journals in developing countries, I raise the issue as to whether it is in the interests of the local journals that you should publish such articles. Is it not derogatory to the improvement of the standards and circulation of such journals ? Are the articles of more worldwide significance than of local interest ? On what basis do you make your selection ? -The issue cannot be avoided by replying that you are not responsible for the submissions (and I admit to personal guilt!). It is a serious point as to whether you should encourage overseas authors by accepting the cream of articles, or whether you should support the development of local journals by referring back all articles for first refusal by the local journal. The criteria for acceptance are critical. The essence of this letter is to point out that the mere publication of such figures without an accompanying" explanation (is there a distinction between " signed articles and " signed contributions " ?) of editorial policy and intent is somewhat valueless-though perhaps ego-inflating on first sight. And to stimulate you into publishing a clear statement-or have I missed the relevant editorial ?
since, in
serum, in their action
against Pseudomonas.4
Pharmax Medical Limited, Bourne Road, Bexley, Kent DA5 1NX.
SUSAN F. SULLMAN, Head of Technical Services Department.
PRIAPISM DURING REGULAR DIALYSIS SIR,--The correspondence following the paper by Dr Port and others (Nov. 30, p. 1287) describes the difficulties of treatment of this condition, particularly when Peyronie’s disease has developed. The most heroic treatment, including surgery, seems to be of little value. May I draw attention to the paper by Heslop et al.5, describing the value of ultrasonic therapy in these cases, which the authors describe as having " material advantages over radiotherapy, surgery, steroid therapy, or other drug administration " ? Manchester Victoria Memorial
Jewish Hospital, Cheetham, Manchester M8 8TT.
BERNARD SANDLER.
PARAQUAT SIR,—The letter of Dr Binnie (Jan. 18, p. 169) about paraquat requires some comment. Inquiry of the Regional Poisons Centres does not confirm his quoted figures. In the United Kingdom in 1974 there were 34 deaths due to paraquat, of which 21 were suicides, 7 of unknown circumstances, and 2 homicidal. The deaths were not concentrated in any particular area as Dr Binnie’s figures might suggest. A recent review of paraquat poisoning6 showed that, at the time of writing, of 97 cases recorded in the medical literature 29 recovered, and our own records of other cases confirm this proportion. It is to be hoped that the recently suggested treatmentwill improve these figures. The ethical justification for the continued use of paraquat must be in its great value in helping food production. Due to its unique properties it is at present irreplaceable by other herbicides in most applications. In well over 100 countries 3. 4.
Castle, A. R., Elstub, J. J. clin. Path. 1971, 24, 773. Davis, S. D., Iannetta, A., Wedgwood, R. O. J. infect. Dis. 1971, 123, 392.
5. Heslop, R. W., Oakland, D. J., Maddox, B. T. Br. J. Urol. 1967, 39. 6. Fletcher, K., in Forensic Toxicology (edited by B. Ballantyne); p. 86. Bristol, 1974. 7. Smith, L. L., Wright, A., Wyatt, I., Rose, M. S. Br. med. J. 1974, iv, 569.
indispensable. Imperial Chemical Industries Limited, Alderley Park, near Macclesfield, Cheshire SK10 4TJ.
K. FLETCHER.
Department of Tropical Community Health,
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA.
REX FENDALL.
**Our note was deliberately terse: good readers, like good eaters, are usually concerned more with the fare that is placed before them than with the source of the ingredients that
included or excluded. But this short note its like (3 column-inches), predecessors covering the years from 1966 onwards, may have had some slight value in providing evidence and solace to disappointed authors who had been notified in the previous twelve months that their were
279 be declined for lack of space. The to those fascinated by the capacity for rapid international communication which has evolved in the past thirty years. The Lancet has no bias towards or against contributions (i.e., articles and Letters to the Editor) from any one continent or any one country; and no-one in Adam Street has the faintest notion of how the latest annual return will differ from the previous year’s until the calculations have been feverishly completed at the end of December. Professor Fendall’s third point-the interests of local journals-does not concern only developing countries: it was being debated three decades ago in developed regions (including Australasia and Scandinavia) which have local journals. Such journals, it then seemed, became reconciled to losing many articles that were of more than local interest to U.S. or U.K. journals with a wider circulation. It is difficult to see how otherwise the information in these articles can be surely and quickly disseminated; even the most determined reader cannot hope to scan all local journals. Last week (p. 210) The Lancet published an article on experience with a mortality committee in a hospital in Kenya. The author concluded that the approach he described might prove helpful in most hospitals in developing countries. Professor Fendall would evidently have had us suggest to the author that he publish his findings in East Africa. The author might well have decided against adopting this suggestion; and, if so, he would, we believe, have been right.-ED. L.
contributions
note may
also
must
appeal
ORAL BACTERIAL VACCINE AND COLDS Sn:,—In a similar manner to that of Dr Tyrrell (Jan. 11, p. 108), our trialwas conducted on strict double-blind lines. There was no difference in the frequency and duration of colds in the two groups, whereas the severity as judged by the number of days absent showed a statistically significant reduction in the vaccine group. Our methods of recording, 1972-73, differed in that the school boarders were throughout the trial period observed by the matron and medical staff. Our experience has shown that the method of retrospective subjective impressions of colds taken at the end of a trial usually is of little value compared with the method of parallel current study. We have found a similar result with this vaccine in patients with chronic bronchitis in the older age-groups. The reduction in the number of days absent in the vaccine group was of the same order from 10-17 years, suggesting that natural acquired immunity did not occur. In their report2 Tyrrell et al. mention the work of Tomasi et awl. on the IgA local secretory antibody system. Further study’along these lines is indicated by our results. Western Hospital, London SW6.
H. C. PRICE.
Bristol.
G. HENLEY.
HETEROZYGOTE ADVANTAGE IN CYSTIC FIBROSIS SiR,—Commenting on the recent correspondence (Jan. 18, p. 167) on the as yet unidentified biological advantage that theory demands the cystic-fibrosis heterozygote to possess, would it be too fanciful to suggest that this could lie in an exceptional agreeableness of these individuals ? Such a quality has in my experience been a striking feature of the personalities of mothers of children with cystic fibrosis. Since (until perhaps recent years) 1. Price, M. C., Henley, G. Practitioner, 1974, 213, 720. 2. Tyrrell, D. A. J., Nolan, P. S., Reed, S. E., Healey, M. J. R. Br. J. prev. soc. Med. 1972, 26, 129. 3. Tomasi, T. B., Tan, E., Solomon, A., Prendergast, R. A. J. exp. Med. 1965, 131, 101.
populations have had an excess of females over males of marriageable age, exceptionally agreeable females would presumably carry a reproductive advantage. Department of Pædiatrics, Addenbrooke’s Hospital, Cambridge CB2 2QQ.
DOUGLAS GAIRDNER.
KANAM MANDIBLE’S TUMOUR SiR,-Since suggested diagnoses often become firmly entrenched in medical folk lore, I feel that Dr Stathopoulos’s suggestion (Jan. 18, p. 165) that the Kanam mandible may have been the seat of Burkitt’s lymphoma should be closely examined. " The interpretation of archaic pathology is often a task of extreme complexity " and " in palaeopathology the best opinions are often tentative opinions ".1 The changes in the Kanam mandible (interpreted by Tobias as a subperiosteal ossifying sarcoma) have been by Brothwell as a malignant tumour in which accepted " osteosarcomafit’ the macroscopic picture well although there is some difference of opinion on this diagnosis ".2 Goldstein believes the lesion to be a " sarcomatous overgrowth ".3Wells, however, states that the Kanam mandible has been " diagnosed as a sarcoma but its present status is doubtful ".4 I have also expressed reservations.5I) I feel that the changes might have resulted from any process elevating the periosteum and it is interesting to note that Brothwell, before opting for osteosarcoma, considered the possibility of trauma and low-grade inflammation with much subperiosteal new bone. I would suggest, therefore, that it is premature to consider too seriously the question of Burkitt’s lymphoma in this mid-Pleistocene fossil. It is by no means proven that the changes are even neoplastic. -
University Pathology Department, Western Infirmary, Glasgow G11 6NT.
A. T. SANDISON.
INTESTINAL ABSORPTION OF GLUCOSE SiR,—We were impressed by the work of Dr Read and others (Sept. 14, p. 624) in measuring the kinetics of glucose absorption by means of transmural electrical potentials in the jejunum. We were further gratified by the attention they devoted to our own studies, but we should like to respond to two of the issues they raised during a comparison of results. First, our use of prolonged infusion periods and of transintestinal intubation were not, as Read et al. said, necessitated by instability of the measured potential differences (P.D.S). In fact, our P.D.S were invariably stable within 15 minutes of each infusion. Using constant infusion-rates, we did not observe any motility-induced fluctuations of P.D., and the effects of any transient fluctuations (as well as of A.c. interference) were eliminated simply by attaching a 0-1 .F capacitor across the input poles of our potentiometer, without our having to resort to pharmacological manipulations such as propantheline. Our use of prolonged infusion periods and of transintestinal intubation were dictated rather by other aspects of experimental design, since we were simultaneously carrying out many additional measurements (reported separately) of net glucose, water, and electrolyte fluxes over multiple Wells, C. in Diseases in Antiquity (edited by D. Brothwell and A. T. Sandison); p. 5. Springfield, Illinois, 1967. 2. Brothwell, D. ibid. p. 330. 3. Goldstein, M. S. in Science in Archæology (edited by D. Brothwell and E. Higgs); p. 485. London, 1969. 4. Wells, C. Bones, Bodies and Disease; p. 75. London, 1964. 5. Sandison, A. T. in The Skeletal Biology of Earlier Human Populations (edited by D. Brothwell); p. 230. Oxford, 1968. 1.
