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MILEAGE FUND INCREASED
112 results in the treatment of major and minor epilepsy in childhood with the ketogenic diet, which he shows to be. twice as effective as phenytoin or phenobarbitone, either singly or in combination. Drugs should only be used, in Peterman’s view, if the ketogenic diet is impractical or impossible. Petit mal may then be treated with , Tridione’ ; withParadione,’ a close relation of tridione that may also cause trouble ’in the bone-marrow occasionally ; or’withThypbenytoin,’ one of the hydantoins, which is useful in both grand and petit mal and less toxic than phenytoin. When tridione or paradione are used, phenobarbitone should be added to prevent the occurrence of major fits. For the latter, Peterman believes phenobarbitone to be the most reliable and effective drug, with the lowest incidence of side-effects. Thus it is doubly superior to phenytoin, the efficacy of which he holds to have been greatly exaggerated. PENICILLIN AUGMENTATION IN BACTERIAL ENDOCARDITIS
BACTERIA vary considerably in their sensitivity to from those, such as the hæmolytic streptococcus, which readily succumb, through a number of less sensitive organisms to the coli-typhoid group and others, which are scarcely sensitive to this antibiotic at all. Before the introduction of penicillin, subacute bacterial endocarditis was one of the almost invariably fatal diseases, though a small proportion of successes with sulphonamides had broken its spell. As soon as enough penicillin was obtainable it was used in an increasing number of cases. The dosage required was very high, relapses commonly necessitated a further course, and by then the causative organism had often become less sensitive to the drug. Strep. viridans, the usual causative organism, belongs to the intermediate group of bacteria which are rather less sensitive to penicillin, and heavy dosage is also necessary to enable an effective concentration of penicillin to penetrate the endocardial vegetations. In this issue Professor Stuart-Harris and his colleagues report on the effect of combining penicillin withCaronamide’ to obtain a higher bloodTwo patients remained well for level of penicillin. 5 months after this combined therapy when they had relapsed after repeated courses of penicillin alone ; while in a third case a brief course of caronamide during penicillin therapy led to clinical improvement which had not occurred before. Caronamide (4’carboxyphenylmethane-sulphonanilide) blocks the excretion of penicillin without noticeably damaging the kidneys.l Toxic symptoms recorded during caronamide therapy are transitory renal disturbances, with albumin -and occasional red cells in the urine, while a few cases have developed rashes. In the present cases all there patients complained of nausea, which The dosage adopted was eased by phenobarbitone. was 4 g. four-hourly ; perhaps if the caronamide had been. given at the same rate of 1 g. per hour but more frequently than four-hourly this symptom might have been less troublesome. One patient had fever and and lumbar cedema was noted but no rash, leucopenia in 2 cases. This suggested some temporary renal impairment, but the urea-clearance test at the time was normal and the oedema soon subsided. In resistant cases anatomical peculiarities may hinder the diffusion of the penicillin into the endocardial vegetations ; this may explain the failure in the first case. Caronamide is precipitated in an acid urine (below pH 5-5), so it may be desirable to alkalinise the urine, and a daily urinary output of at least 1500 ml. should be maintained while the caronamide is being given.
penicillin,
K. H., Russo, H. F., Patch, E. A., Tillson, E. K., Shanes, G. J. Pharmacol. 1947, 91, 272. See leading article, Lancet, 1948, i. 70.
1. Beyer,
UREA-SULPHONAMIDE THERAPY in the 1914-18 war that urea was first used for
IT was the treatment of infected war wounds. Then it seems to have fallen into disuse until 1937, when Holder and Mackayreported the effective treatment of infected or potentially infected wounds with sulphonamide-urea mixtures containing about 10% of urea. These workers claimed that urea was non-irritating to tissues and exerted its beneficial action by dissolving the pus and necrotic debris of wounds, which contains sulphonamide inhibitors. They also showed that urea increases the solubility of sulphanilamide and sulphadiazine in tissue fluids and that in vitro the bacteriostatic effect of sulphanilamide against Bact. coli is increased tenfold by the addition of 5% urea. Tsuchiya and his co-workersextended these observations to other sulphonamides and showed in vitro that urea significantly increases their bacteriostatic effect even in the presence of known sulphonamide inhibitors such as p-aminobenzoic acid and methionine. Perhaps more important, they demonstrated that strains of sulphathiazole-resistant staphylococci in a synthetic medium were susceptible to combinations of urea and sodium sulphathiazole. The development of sulphonamide resistance has now become of considerable practical importance in therapeutics, and any agent which may overcome this resistance deserves careful study. The local use of urea with sulphonamides is now well established, but urea is likely to be of greater therapeutic value in the treatment of sulphonamide-resistant infections, particularly those not amenable to treatment with penicillin. Apart from increasing the bacteriostatic action of the sulphonamides, urea increases their solubility, so that large doses can be given without fear of crystalluria. La Londe and Gardner3 have treated five cases of meningitis with urea and sulphadiazine. The adult dose of urea was 30 g. four-hourly by mouth. One case was due to Bad. fœcalis alkaligenes, which did not respond to penicillin and sulphadiazine alone, and in which streptomycin was not tolerated. Another was a case of meningitis due to Friedländer’s bacillus, which developed while the patient was receiving prophylactic doses of penicillin. There were also two cases of meningitis due to ,Bact. coli and one probably due to Staphylococcus albus. There was good evidence that the urea-sulphonamide therapy was responsible for these patient’s recovery, .and since it is simple. safe, and inexpensive it merits trial in sulphonamideresistant infections before resorting to streptomycin. MILEAGE FUND INCREASED
representations on behalf of rural pracititoners made by the general medical services committee of the British Medical Association at a meeting with the Ministry of Health on Dec. 22. The Ministry hag responded by raising the Mileage Fund, now standing at n,300,00O per annum, to £2,000,000, the increase being retrospective from July 5. Of the S700,000 increase, E200,000 comes from the Special Inducement Fund and £500,000 is new money. The change means that the total sum now paid to rural practitioners for mileage will be about four times as large as that paid under National Health Insurance. If as many as a quarter of practitioners were defined as rural, the average At sum drawn by each would still be nearly E400. the cost of removing half of the Special Inducement Fund, the new arrangement will bring help to many of the doctors with relatively small practices who have been hit most hard by the loss of private patients. But not to all. URGENT
were
Holder, H. G., Mackay, E. M. J. Amer. med. Ass. 1937, 108, 1167; Milit. Surg. 1942, 90, 509 ; Surgery, 1943, 13, 677. See also Muldavin, L. F., Holtzmann, J. M. Lancet, 1938, i, 549. 2. Tsuchiya, H. M., Tenenberg, D. J., Clark, W. G., Strakosch, E. A Proc. Soc. exp. Biol., N.Y. 1942, 50, 262 ; Ibid, 51, 245. 3. La Londe, A. A., Gardner, W. J. J. Amer. med. Ass. 1948, 1.
138, 406.
BACTERIA vary considerably in their sensitivity to from those, such as the hæmolytic streptococcus, which readily succumb, through a number of less sensitive organisms to the coli-typhoid group and others, which are scarcely sensitive to this antibiotic at all. Before the introduction of penicillin, subacute bacterial endocarditis was one of the almost invariably fatal diseases, though a small proportion of successes with sulphonamides had broken its spell. As soon as enough penicillin was obtainable it was used in an increasing number of cases. The dosage required was very high, relapses commonly necessitated a further course, and by then the causative organism had often become less sensitive to the drug. Strep. viridans, the usual causative organism, belongs to the intermediate group of bacteria which are rather less sensitive to penicillin, and heavy dosage is also necessary to enable an effective concentration of penicillin to penetrate the endocardial vegetations. In this issue Professor Stuart-Harris and his colleagues report on the effect of combining penicillin withCaronamide’ to obtain a higher bloodTwo patients remained well for level of penicillin. 5 months after this combined therapy when they had relapsed after repeated courses of penicillin alone ; while in a third case a brief course of caronamide during penicillin therapy led to clinical improvement which had not occurred before. Caronamide (4’carboxyphenylmethane-sulphonanilide) blocks the excretion of penicillin without noticeably damaging the kidneys.l Toxic symptoms recorded during caronamide therapy are transitory renal disturbances, with albumin -and occasional red cells in the urine, while a few cases have developed rashes. In the present cases all there patients complained of nausea, which The dosage adopted was eased by phenobarbitone. was 4 g. four-hourly ; perhaps if the caronamide had been. given at the same rate of 1 g. per hour but more frequently than four-hourly this symptom might have been less troublesome. One patient had fever and and lumbar cedema was noted but no rash, leucopenia in 2 cases. This suggested some temporary renal impairment, but the urea-clearance test at the time was normal and the oedema soon subsided. In resistant cases anatomical peculiarities may hinder the diffusion of the penicillin into the endocardial vegetations ; this may explain the failure in the first case. Caronamide is precipitated in an acid urine (below pH 5-5), so it may be desirable to alkalinise the urine, and a daily urinary output of at least 1500 ml. should be maintained while the caronamide is being given.
penicillin,
K. H., Russo, H. F., Patch, E. A., Tillson, E. K., Shanes, G. J. Pharmacol. 1947, 91, 272. See leading article, Lancet, 1948, i. 70.
1. Beyer,
UREA-SULPHONAMIDE THERAPY in the 1914-18 war that urea was first used for
IT was the treatment of infected war wounds. Then it seems to have fallen into disuse until 1937, when Holder and Mackayreported the effective treatment of infected or potentially infected wounds with sulphonamide-urea mixtures containing about 10% of urea. These workers claimed that urea was non-irritating to tissues and exerted its beneficial action by dissolving the pus and necrotic debris of wounds, which contains sulphonamide inhibitors. They also showed that urea increases the solubility of sulphanilamide and sulphadiazine in tissue fluids and that in vitro the bacteriostatic effect of sulphanilamide against Bact. coli is increased tenfold by the addition of 5% urea. Tsuchiya and his co-workersextended these observations to other sulphonamides and showed in vitro that urea significantly increases their bacteriostatic effect even in the presence of known sulphonamide inhibitors such as p-aminobenzoic acid and methionine. Perhaps more important, they demonstrated that strains of sulphathiazole-resistant staphylococci in a synthetic medium were susceptible to combinations of urea and sodium sulphathiazole. The development of sulphonamide resistance has now become of considerable practical importance in therapeutics, and any agent which may overcome this resistance deserves careful study. The local use of urea with sulphonamides is now well established, but urea is likely to be of greater therapeutic value in the treatment of sulphonamide-resistant infections, particularly those not amenable to treatment with penicillin. Apart from increasing the bacteriostatic action of the sulphonamides, urea increases their solubility, so that large doses can be given without fear of crystalluria. La Londe and Gardner3 have treated five cases of meningitis with urea and sulphadiazine. The adult dose of urea was 30 g. four-hourly by mouth. One case was due to Bad. fœcalis alkaligenes, which did not respond to penicillin and sulphadiazine alone, and in which streptomycin was not tolerated. Another was a case of meningitis due to Friedländer’s bacillus, which developed while the patient was receiving prophylactic doses of penicillin. There were also two cases of meningitis due to ,Bact. coli and one probably due to Staphylococcus albus. There was good evidence that the urea-sulphonamide therapy was responsible for these patient’s recovery, .and since it is simple. safe, and inexpensive it merits trial in sulphonamideresistant infections before resorting to streptomycin. MILEAGE FUND INCREASED
representations on behalf of rural pracititoners made by the general medical services committee of the British Medical Association at a meeting with the Ministry of Health on Dec. 22. The Ministry hag responded by raising the Mileage Fund, now standing at n,300,00O per annum, to £2,000,000, the increase being retrospective from July 5. Of the S700,000 increase, E200,000 comes from the Special Inducement Fund and £500,000 is new money. The change means that the total sum now paid to rural practitioners for mileage will be about four times as large as that paid under National Health Insurance. If as many as a quarter of practitioners were defined as rural, the average At sum drawn by each would still be nearly E400. the cost of removing half of the Special Inducement Fund, the new arrangement will bring help to many of the doctors with relatively small practices who have been hit most hard by the loss of private patients. But not to all. URGENT
were
Holder, H. G., Mackay, E. M. J. Amer. med. Ass. 1937, 108, 1167; Milit. Surg. 1942, 90, 509 ; Surgery, 1943, 13, 677. See also Muldavin, L. F., Holtzmann, J. M. Lancet, 1938, i, 549. 2. Tsuchiya, H. M., Tenenberg, D. J., Clark, W. G., Strakosch, E. A Proc. Soc. exp. Biol., N.Y. 1942, 50, 262 ; Ibid, 51, 245. 3. La Londe, A. A., Gardner, W. J. J. Amer. med. Ass. 1948, 1.
138, 406.