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ORAL DIURETICS
242 and a slight fall in pH. In those patients who did not respond to diomax, it was shown that this was not due to failure to absorb the drug from the alimentary tract. Clearly, further reports of the trials of carbonic anhydrase inhibitors will be of interest and importance.
ORAL DIURETICS AN oral diuretic that was as effective and safe
as the would save much time preparations parenteral and money. For ten years now various organic preparations of mercury have been given orally, but there is a risk of fatal poisoning, and toxic effects occur in up to NEW MENINGO-ENCEPHALITIS VIRUSES 50% of patients. The most favourable report to date is LAST year there was an epidemic of aseptic meningitis that of Dimitroff et al.1 who used an experimental at Port Augusta in South Australia. Most of the cases organic preparation containing 10 mg. of mercury in each were mild ; but there was one death, of a mongol child enteric-coated tablet. The drug was given in divided aged 13 months. From the brain of this child Miles and doses to a total of 60 to 100 mg. of mercury per week. Dane1 isolated a new virus which seems to have been Of 35 ambulant patients with chronic congestive heartfor the The virus was recovered responsible failure, 6 (17%) became intolerant to the drug, and had by inoculating an epidemic. extract of the brain, cerebrospinal cramp-like abdominal pain, nausea, vomiting, diarrhoea, fluid, and meninges into cortisone-treated mice. These or an unpleasant taste in the mouth. But in the remainder were used because of a report 2 that cortisone increased the drug replaced intramuscular ’Mercuhydrin ’ quite the susceptibility of hamsters to type-2 poliomyelitis effectively for periods up to eleven months. The authors virus; and Miles and Dane found that in mice injected stress that oral preparations are only useful in mainwith the original extract in the absence of cortisone, tenance therapy when the acute phase of congestive infection did not develop. On further passages in mice, heart-failure has been successfully treated by injected meningitis with a mononuclear-cell reaction and myositis mercurials. were produced. The Port Augusta virus is one of the Since a good number of physicians are probably still viruses and it shares some morphological and larger sceptical about the usefulness of oral mercurials, it is growth characters with the viruses of the psittacosis encouraging to see that other fields are being skilfully group. Serologically, however, it is unrelated to psittaexplored. One of the most promising lines of study seems cosis, mumps, and lymphocytic choriomeningitis viruses ; to be that of carbonic-anhydrase inhibitors. These and it is resistant to penicillin and streptomycin in ovo. renal tubular excretion of agents impair hydrogen ions Complement-fixation tests with sera from patients who and reabsorption of sodium and potassium ions. The had recovered from aseptic meningitis suggest that the sulphonamide group of drugs are mild carbonic-anhydrase Port Augusta virus was the cause of the epidemic. inhibitors, and in fact Schwartz2 has used sulphanilamide About six months before the South Australia epidemic as a diuretic. The search for less-toxic and more potent an outbreak of encephalitis occurred a few hundred miles has now progressed further, and a likely drug is agents From samples of further east, in the Sydney area. " compound 6063 " (2-acetylamino-l, 3, 4-thiadiazole-5- faeces taken in eleven cases during the course of the sulphonamide), known as ’Diomax.’ This is the prepara- disease, Stanley et al.3 isolated a hitherto undescribed tion used by Berliner et al.3 in their study of the virus. This virus is quite different from the Port Augusta relation between urinary acidification and potassium virus, and Stanley et al. suggest including it in the metabolism. Friedberg et awl. have lately described a Coxsackie group. Experimental infection with this virus clinical trial of this drug in patients with congestive is produced only in suckling mice less than twenty-four heart-failure. Two series of patients were studied : 11 hours old, in which it causes a diffuse encephalitis without patients who required hospital treatment for uncon- skeletal-muscle or pancreatic lesions. Serologically this trolled congestive heart-failure ; and 15 patients who virus, though related slightly to one of the Coxsackie-B had survived an acute episode and were able to get about group, has distinctive features ; and Stanley et al. on maintenance treatment. In all patients, diomax would place it in a new.group, C. Neutralisation tests a diuretic, supplementing as replaced parenteral mercury with paired sera of patients from the outbreak showed other measures, such as rest or graded exercise, digitalis, that antibodies to the Coxsackie-C virus developed and sodium restriction. The trial was not very strictly early in the disease an d persisted for some time afterwards. controlled, but the data suggest that diomax may have These reports deal with the viruses isolated rather than considerable clinical usefulness. In 9 of the 11 hospital the detailed clinical and epidemiological findings, which patients clinical response to diomax was satisfactory, but will be awaited with interest. Afzelius-Alm4 investithe remaining 2 patients had to have parenteral mergated a series of cases of aseptic meningitis and encephacurials. In 9 of the 15 ambulant patients diomax could litis and recovered the viruses of mumps and herpes be satisfactorily substituted for mercurial injections, but simplex in a small proportion of cases. In the majority the other 6 patients had to return to injections. The of cases he recovered no virus, and most investigators most effective dosage of diomax was 250 to 750 mg. have had the same experience. It will be interesting to orally every eight hours for two to three days, during see whether the addition of cortisone-treated mice and which time the excretion of water, sodium, and potassium newly born mice to the laboratory menage will increase An rose and then gradually diminished to control levels. the proportion of successful virus isolations.
mercurial
interval of forty-eight hours or more was then required before a further diuretic response to diomax could be obtained. Alternatively, the drug could be given once daily in 250 mg. doses without tolerance developing. Mild acidosis occurred during treatment,- but this did not seem to have any appreciable connection with the sodium and water loss. Only minor side-effects were encountsred, the chief being drowsiness, lassitude, and parnesthesiae in the digits, but they were never bad enough to warrant stopping the drug. The only significant changes in blood chemistry were a fall in plasma carbon dioxide content Dimitroff, S. P., Thorner, M. C., Griffith, 1953, 7, 380. 2. Schwartz, W. B. New Engl. J. Med. 1949, 3. Berliner, R. W., Kennedy, T. J. jun., Orloff, 1951, 11, 274. 4. Friedberg, C. K., Taymor, R., Minor, J. B., Engl. J. Med. 1953, 240, 883. 1.
G. C.
Circulation,
240, 173. J.
Amer. J. Med.
Halpern, M.
New
Mr. A. A. GEMMELL has been re-elected president of the of Obstetricians and Gynaecologists for 1953-54.
Royal College
Dr. G. E. ViLVANDBB, consulting London Hospital, died on July 26.
radiologist to
the
GORDON, F.R.S., died at his home at July 26 at the age of 81. WE also regret to announce the death on July 26 in Edinburgh of Miss M. C. TOD, F.F.R., deputy director of the Christie Hospital, and Holt Radium Institute, Dr. MERVYN East Molesey on
Manchester. 1. Miles, J. A. R., Dane, D. M. S. Med. J. Aust. 1953, i, 884. 2. Schwartzman, G., Fisher, A. J. exp. Med. 1952, 95, 347. 3. Stanley, N. F., Dorman, D. C., Ponsford, J. Aust. J. exp. Biol. med. Sci. 1953, 31, 31. 4. Afzelius-Alm, L. Acta med. scand. 1951, suppl. 263.
ORAL DIURETICS AN oral diuretic that was as effective and safe
as the would save much time preparations parenteral and money. For ten years now various organic preparations of mercury have been given orally, but there is a risk of fatal poisoning, and toxic effects occur in up to NEW MENINGO-ENCEPHALITIS VIRUSES 50% of patients. The most favourable report to date is LAST year there was an epidemic of aseptic meningitis that of Dimitroff et al.1 who used an experimental at Port Augusta in South Australia. Most of the cases organic preparation containing 10 mg. of mercury in each were mild ; but there was one death, of a mongol child enteric-coated tablet. The drug was given in divided aged 13 months. From the brain of this child Miles and doses to a total of 60 to 100 mg. of mercury per week. Dane1 isolated a new virus which seems to have been Of 35 ambulant patients with chronic congestive heartfor the The virus was recovered responsible failure, 6 (17%) became intolerant to the drug, and had by inoculating an epidemic. extract of the brain, cerebrospinal cramp-like abdominal pain, nausea, vomiting, diarrhoea, fluid, and meninges into cortisone-treated mice. These or an unpleasant taste in the mouth. But in the remainder were used because of a report 2 that cortisone increased the drug replaced intramuscular ’Mercuhydrin ’ quite the susceptibility of hamsters to type-2 poliomyelitis effectively for periods up to eleven months. The authors virus; and Miles and Dane found that in mice injected stress that oral preparations are only useful in mainwith the original extract in the absence of cortisone, tenance therapy when the acute phase of congestive infection did not develop. On further passages in mice, heart-failure has been successfully treated by injected meningitis with a mononuclear-cell reaction and myositis mercurials. were produced. The Port Augusta virus is one of the Since a good number of physicians are probably still viruses and it shares some morphological and larger sceptical about the usefulness of oral mercurials, it is growth characters with the viruses of the psittacosis encouraging to see that other fields are being skilfully group. Serologically, however, it is unrelated to psittaexplored. One of the most promising lines of study seems cosis, mumps, and lymphocytic choriomeningitis viruses ; to be that of carbonic-anhydrase inhibitors. These and it is resistant to penicillin and streptomycin in ovo. renal tubular excretion of agents impair hydrogen ions Complement-fixation tests with sera from patients who and reabsorption of sodium and potassium ions. The had recovered from aseptic meningitis suggest that the sulphonamide group of drugs are mild carbonic-anhydrase Port Augusta virus was the cause of the epidemic. inhibitors, and in fact Schwartz2 has used sulphanilamide About six months before the South Australia epidemic as a diuretic. The search for less-toxic and more potent an outbreak of encephalitis occurred a few hundred miles has now progressed further, and a likely drug is agents From samples of further east, in the Sydney area. " compound 6063 " (2-acetylamino-l, 3, 4-thiadiazole-5- faeces taken in eleven cases during the course of the sulphonamide), known as ’Diomax.’ This is the prepara- disease, Stanley et al.3 isolated a hitherto undescribed tion used by Berliner et al.3 in their study of the virus. This virus is quite different from the Port Augusta relation between urinary acidification and potassium virus, and Stanley et al. suggest including it in the metabolism. Friedberg et awl. have lately described a Coxsackie group. Experimental infection with this virus clinical trial of this drug in patients with congestive is produced only in suckling mice less than twenty-four heart-failure. Two series of patients were studied : 11 hours old, in which it causes a diffuse encephalitis without patients who required hospital treatment for uncon- skeletal-muscle or pancreatic lesions. Serologically this trolled congestive heart-failure ; and 15 patients who virus, though related slightly to one of the Coxsackie-B had survived an acute episode and were able to get about group, has distinctive features ; and Stanley et al. on maintenance treatment. In all patients, diomax would place it in a new.group, C. Neutralisation tests a diuretic, supplementing as replaced parenteral mercury with paired sera of patients from the outbreak showed other measures, such as rest or graded exercise, digitalis, that antibodies to the Coxsackie-C virus developed and sodium restriction. The trial was not very strictly early in the disease an d persisted for some time afterwards. controlled, but the data suggest that diomax may have These reports deal with the viruses isolated rather than considerable clinical usefulness. In 9 of the 11 hospital the detailed clinical and epidemiological findings, which patients clinical response to diomax was satisfactory, but will be awaited with interest. Afzelius-Alm4 investithe remaining 2 patients had to have parenteral mergated a series of cases of aseptic meningitis and encephacurials. In 9 of the 15 ambulant patients diomax could litis and recovered the viruses of mumps and herpes be satisfactorily substituted for mercurial injections, but simplex in a small proportion of cases. In the majority the other 6 patients had to return to injections. The of cases he recovered no virus, and most investigators most effective dosage of diomax was 250 to 750 mg. have had the same experience. It will be interesting to orally every eight hours for two to three days, during see whether the addition of cortisone-treated mice and which time the excretion of water, sodium, and potassium newly born mice to the laboratory menage will increase An rose and then gradually diminished to control levels. the proportion of successful virus isolations.
mercurial
interval of forty-eight hours or more was then required before a further diuretic response to diomax could be obtained. Alternatively, the drug could be given once daily in 250 mg. doses without tolerance developing. Mild acidosis occurred during treatment,- but this did not seem to have any appreciable connection with the sodium and water loss. Only minor side-effects were encountsred, the chief being drowsiness, lassitude, and parnesthesiae in the digits, but they were never bad enough to warrant stopping the drug. The only significant changes in blood chemistry were a fall in plasma carbon dioxide content Dimitroff, S. P., Thorner, M. C., Griffith, 1953, 7, 380. 2. Schwartz, W. B. New Engl. J. Med. 1949, 3. Berliner, R. W., Kennedy, T. J. jun., Orloff, 1951, 11, 274. 4. Friedberg, C. K., Taymor, R., Minor, J. B., Engl. J. Med. 1953, 240, 883. 1.
G. C.
Circulation,
240, 173. J.
Amer. J. Med.
Halpern, M.
New
Mr. A. A. GEMMELL has been re-elected president of the of Obstetricians and Gynaecologists for 1953-54.
Royal College
Dr. G. E. ViLVANDBB, consulting London Hospital, died on July 26.
radiologist to
the
GORDON, F.R.S., died at his home at July 26 at the age of 81. WE also regret to announce the death on July 26 in Edinburgh of Miss M. C. TOD, F.F.R., deputy director of the Christie Hospital, and Holt Radium Institute, Dr. MERVYN East Molesey on
Manchester. 1. Miles, J. A. R., Dane, D. M. S. Med. J. Aust. 1953, i, 884. 2. Schwartzman, G., Fisher, A. J. exp. Med. 1952, 95, 347. 3. Stanley, N. F., Dorman, D. C., Ponsford, J. Aust. J. exp. Biol. med. Sci. 1953, 31, 31. 4. Afzelius-Alm, L. Acta med. scand. 1951, suppl. 263.