ENCEPHALOPATHY IN MICE
1
327 for several years now, and has stood the test of time in the treatment of severe infections with Ps. pyocyanea, but no- one has yet had the audacity to suggest that it is effective in the wide range of conditions for which colistin is now being advocated. In your annotation you claim that " an important advantage of colistin over polymyxin B is its lower neuro- and nephro-toxicity ". Are you referring to the unsubsti- tuted or substituted molecules ? I venture to suggest that the unmodified substances do not differ in nephrotoxicity, but there is evidence that the methane sulphonate of polymyxin B is not toxic and is effective therapeutically.13 The form of colistin issued for intramuscular use is also the methane sulphonate. If the similarity between colistin and polymyxin is fortuitous, it is a remarkable scientific coincidence; if the similarity is not fortuitous, the situation is equally re- markable, with implications which are not only scientific. Carshalton, Surrey. G. T. STEWART. G. T. STEWART. ACCIDENTAL HYPOTHERMIA AND PANCREATITIS JOSEPH STOKES Director, Hawaii Cardiovascular Study. The Queen’s Hospital, Honolulu. SIR,-Two articles 14 15 drew attention to the clinical and pathological evidence of pancreatitis which may accompany accidental hypothermia. In view of the well- accepted, although as yet unexplained, association of alcoholism and pancreatitis, I wonder whether the authors of either article have considered that a dram or so of Scotch whisky taken by these patients to fend off the cold which soon proved to be their undoing might partly explain the acute and chronic changes in the pancreas. Fortunately, here in the South Pacific one runs less risk when using alcohol as fortification against the cooling effect of the Trade Winds. ENCEPHALOPATHY IN MICE A. M. G. CAMPBELL. SIR,-I was very interested in the observations of Dr. Chandler (Jan. 13). I think we should bear in mind the importance of his work on scrapie in relation to human diseases of the nervous system, such as disseminated sclerosis, whilst realising that scrapie is not a demyelinat- ing disease. It is obvious that degenerative changes associated with scrapie can affect more than one breed of animal and it seems important to realise that there may be an agent which resists normal killing methods and can produce the degenerative diseases of the nervous system by intracerebral inoculation after a long incubation period, and in which varying susceptibilities are shown by the animals exposed to this hazard. The difficulties of assessing human disease of a similar type are obvious, but the importance of this concept in relation to disseminated sclerosis, in which symptoms may, in my opinion, develop long after the patient has been exposed to the causative factor, may have hindered the discovery of the true aetiology of disseminated sclerosis. The accounts of occasional conjugal disseminated sclerosis may, of course, be explained by concidence, but I have described cases of disseminated sclerosis occurring in groups which seem difficult to explain unless they have been exposed to some common causative factor. I am sure that we should not underemphasise the importance of veterinary work in relation to human disease, 13. Clifford, H. E., Stewart, G. T. ibid. p. 177. 14. Duguid, H., Simpson, R. G., Stowers, J. M. Lancet, 1961, ii, 1213. 15. Read, A. E., Emslie-Smith, D., Gough, K. R., Holmes, R. ibid. p. 1219. particularly in diseases of the central nervous system, and particularly in diseases such as scrapie, which almost suggests a new concept of certain diseases. Bristol. GRISEOFULVIN IN FUNGOUS DISEASES OF THE SKIN SIR,-It has been found that griseofulvin, after oral ingestion, is more effectively absorbed if its fineness is increased.’ 2 In the form in which the drug has hitherto been available, the fineness has not been closely controlled, but the average particle size has been of the order of 12 fL (specific surface area approximately 0’35 sq. m. per g.). As the fineness is increased from this level, the effect in terms of better absorption is initially considerable, then grad- ually decreases. With an average particle size of 2.7 fL (specific surface area approximately 1-5 sq. m. per g.), which for a number of technical reasons is the practical limit, it has been found that in man a single dose of 125- mg. will give approxi- mately the same concentration of griseofulvin in the blood as a single dose of 250 mg. of the original fineness. The concen- tration of the drug deposited in the newly formed keratinous layers presumably depends on the blood concentration, and it was therefore a reasonable assumption that 125 mg. of the new fine-particle form would have the same therapeutic effect as 250 mg. of the previous material-i.e., the new form would be as effective as the original but at half the dose. We therefore carried out a clinical trial with the new griseo- fulvin over the past nine months. Since the efficacy of griseo- RESULTS OF TREATMENT OF FUNGOUS INFECTIONS OF THE SKIN, HAIR, OR NAILS WITH GRISEOFULVIN a. Cases treated with " new" griseofulvin, 500 mg. daily. b. Cases treated with " new griseofulvin, 250 mg. daily. c. Cases treated with " old griseofulvin, 1000 mg. daily. Figures in group c taken from Harvey et al. 3 fulvin against the fungi causing skin lesions is now well known, we did not consider it necessary to confirm our clinical finding by culture. All the cases treated, however, were confirmed by direct microscopic examination of scales, hairs, or nail parings. Our aim was to determine whether the new preparation was as effective as the original form. 46 cases were treated and the results are set out in the accompanying table. The cases have been divided into five clinical groups. The results with the new griseofulvin have been divided into two groups: (a) those receiving 500 mg. daily (4 tablets); and (b) those receiving 250 mg. daily (2 tablets). A third group (c) (those which received 1000 mg. daily [4 tablets] of the old form) has also been included. These figures have been taken from a previous trial when griseofulvin was first introduced,3 and since the 1. Atkinson, R. M., Bedford, C., Child, K. J., Tomich, E. G. Nature, Lond. (in the press) 2. Duncan, W. A. M., Macdonald, G., Thornton, M. J. (in the press). 3. Harvey, G., Alexander, J. O’D., Kirk, J. F. Scot. med. J. 1960, 5, 51.
Transcript of ENCEPHALOPATHY IN MICE
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for several years now, and has stood the test of time in thetreatment of severe infections with Ps. pyocyanea, but no-one has yet had the audacity to suggest that it is effectivein the wide range of conditions for which colistin is now
being advocated.In your annotation you claim that " an important
advantage of colistin over polymyxin B is its lower neuro-and nephro-toxicity ". Are you referring to the unsubsti-tuted or substituted molecules ? I venture to suggest thatthe unmodified substances do not differ in nephrotoxicity,but there is evidence that the methane sulphonate ofpolymyxin B is not toxic and is effective therapeutically.13The form of colistin issued for intramuscular use is alsothe methane sulphonate.
If the similarity between colistin and polymyxin is
fortuitous, it is a remarkable scientific coincidence; if thesimilarity is not fortuitous, the situation is equally re-markable, with implications which are not only scientific.Carshalton,Surrey. G. T. STEWART.G. T. STEWART.
ACCIDENTAL HYPOTHERMIA AND
PANCREATITIS
JOSEPH STOKESDirector,
Hawaii Cardiovascular Study.The Queen’s Hospital,
Honolulu.
SIR,-Two articles 14 15 drew attention to the clinicaland pathological evidence of pancreatitis which mayaccompany accidental hypothermia. In view of the well-
accepted, although as yet unexplained, association ofalcoholism and pancreatitis, I wonder whether the authorsof either article have considered that a dram or so ofScotch whisky taken by these patients to fend off the coldwhich soon proved to be their undoing might partlyexplain the acute and chronic changes in the pancreas.Fortunately, here in the South Pacific one runs less risk
when using alcohol as fortification against the coolingeffect of the Trade Winds.
ENCEPHALOPATHY IN MICE
A. M. G. CAMPBELL.
SIR,-I was very interested in the observations of Dr.Chandler (Jan. 13). I think we should bear in mind the
importance of his work on scrapie in relation to humandiseases of the nervous system, such as disseminated
sclerosis, whilst realising that scrapie is not a demyelinat-ing disease. It is obvious that degenerative changesassociated with scrapie can affect more than one breed ofanimal and it seems important to realise that there may bean agent which resists normal killing methods and canproduce the degenerative diseases of the nervous systemby intracerebral inoculation after a long incubation period,and in which varying susceptibilities are shown by theanimals exposed to this hazard.The difficulties of assessing human disease of a similar
type are obvious, but the importance of this concept inrelation to disseminated sclerosis, in which symptoms may,in my opinion, develop long after the patient has beenexposed to the causative factor, may have hindered thediscovery of the true aetiology of disseminated sclerosis.The accounts of occasional conjugal disseminated sclerosismay, of course, be explained by concidence, but I havedescribed cases of disseminated sclerosis occurring in
groups which seem difficult to explain unless they havebeen exposed to some common causative factor.
I am sure that we should not underemphasise the
importance of veterinary work in relation to human disease,13. Clifford, H. E., Stewart, G. T. ibid. p. 177.14. Duguid, H., Simpson, R. G., Stowers, J. M. Lancet, 1961, ii, 1213.15. Read, A. E., Emslie-Smith, D., Gough, K. R., Holmes, R. ibid. p. 1219.
particularly in diseases of the central nervous system, andparticularly in diseases such as scrapie, which almostsuggests a new concept of certain diseases.
Bristol.
GRISEOFULVIN IN FUNGOUS DISEASES OFTHE SKIN
SIR,-It has been found that griseofulvin, after oral
ingestion, is more effectively absorbed if its fineness isincreased.’ 2
In the form in which the drug has hitherto been available,the fineness has not been closely controlled, but the averageparticle size has been of the order of 12 fL (specific surface areaapproximately 0’35 sq. m. per g.).As the fineness is increased from this level, the effect in
terms of better absorption is initially considerable, then grad-ually decreases. With an average particle size of 2.7 fL (specificsurface area approximately 1-5 sq. m. per g.), which for anumber of technical reasons is the practical limit, it has beenfound that in man a single dose of 125- mg. will give approxi-mately the same concentration of griseofulvin in the blood asa single dose of 250 mg. of the original fineness. The concen-tration of the drug deposited in the newly formed keratinouslayers presumably depends on the blood concentration, and itwas therefore a reasonable assumption that 125 mg. of the newfine-particle form would have the same therapeutic effect as250 mg. of the previous material-i.e., the new form would beas effective as the original but at half the dose.We therefore carried out a clinical trial with the new griseo-
fulvin over the past nine months. Since the efficacy of griseo-RESULTS OF TREATMENT OF FUNGOUS INFECTIONS OF THE SKIN, HAIR,
OR NAILS WITH GRISEOFULVIN
a. Cases treated with " new" griseofulvin, 500 mg. daily.b. Cases treated with " new griseofulvin, 250 mg. daily.c. Cases treated with " old griseofulvin, 1000 mg. daily.Figures in group c taken from Harvey et al. 3
fulvin against the fungi causing skin lesions is now well known,we did not consider it necessary to confirm our clinical findingby culture. All the cases treated, however, were confirmed bydirect microscopic examination of scales, hairs, or nail parings.Our aim was to determine whether the new preparation was aseffective as the original form. 46 cases were treated and theresults are set out in the accompanying table. The cases havebeen divided into five clinical groups. The results with thenew griseofulvin have been divided into two groups: (a) thosereceiving 500 mg. daily (4 tablets); and (b) those receiving250 mg. daily (2 tablets). A third group (c) (those whichreceived 1000 mg. daily [4 tablets] of the old form) has alsobeen included. These figures have been taken from a previoustrial when griseofulvin was first introduced,3 and since the
1. Atkinson, R. M., Bedford, C., Child, K. J., Tomich, E. G. Nature, Lond.(in the press)
2. Duncan, W. A. M., Macdonald, G., Thornton, M. J. (in the press).3. Harvey, G., Alexander, J. O’D., Kirk, J. F. Scot. med. J. 1960, 5, 51.
