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A MAMMO-RENAL SYNDROME ?
412
precipitating factor: hypertension (2 patients), diabetes mellitus (1), systemic lupus erythematosus (1), and myxredema (1). The 6th patient has a diaphragmatic hernia; an E.C.G. during her stay in hospital showed only T-wave changes, which subsided after a few days, so that it is not clear whether they due to coronary heart-disease. No data are available about the 7th patient. These findings show that myocardial infarction without a precipitating factor is uncommon in women during their productive period. J. SCHARF A. M. NAHIR Department of Internal Medicine A, B. PELED Rambam Government Hospital. A. ASAD. Haifa, Israel.
were
A MAMMO-RENAL SYNDROME ? SIR,-One of my female patients was operated on for bilateral Routine pyelography showed breasts. supernumerary bilateral supernumerary kidneys, with ureters entering independently into the bladder.Another female patient had a unilateral supernumerary breast. Pyelography showed a supernumerary kidney on the same side, ending in a common ureter. Anomalies associated with supernumerary breasts have not been reported. In females, prevalence of supenumerary breasts is about 1 % and the prevalence of kidney reduplication is equally about 1 %. The chance occurrence of the two anomalies in the same patient is 1 in 10,000. I wonder whether aplasia of one breast is not associated -with unilateral renal hypoplasia in some rare instances. Ter Weeden-Zulte, LUC GOEMINNE. Belgium.
ENHANCEMENT OF ANTITUBERCULOSIS-DRUG ACTION BY ACRIDINES
SiR,-Sevag et al.23 have shown that mepacrine (’ Atabrine ’) and other acridines inhibit the development of drug resistance by Staphylococcus spp. and Escherichia coli during continuous incubation in a liquid medium. Lately Warren et al.4 have reported that mepacrine also inhibits development of drug resistance by Mycobacterium tuberculosis. Several acridines have been studied in our laboratory, and several compounds have shown much higher activity than mepacrine. They also inhibit the development of resistance to streptomycin in M. phlei and M. avium. We report here preliminary findings on the influence of acridines on the activity of antituberculosis
drugs. M. tuberculosis, strain H37Rv, was suspended in Sauton medium enriched with bovine serum andTween 80’. Non-bacteriostatic concentrations of acridines were established in preliminary experiments. The activity of antituberculosis drugs was tested by serial dilution in the same medium. The viable count of mycobacteria in each tube was about 2 x 108. Such a large population must have contained resistant mutants, thus increasing the minimal inhibiting concentration (M.l.C.) of the drug. The M.i.c. of each drug (in g. per ml.) greatly diminished when one of the acridines in sub-bacteriostatic concentrations was added, as follows:
The coefficients of activation
were
1250
to
20 for
isoniazid,
(editor) Handbook of Congenital Malformations; p. 17. Rubin, Philadelphia. 1967 2. Sevag, M. G., Ashton, B. Nature, Lond. 1964, 203, 1323-1326. 3. Heller, C. S., Sevag, M. G. Appl. Microbiol. 1966, 14, 879. 4. Warren, G., Gregory, F., Healy, E., Flint, S. Nature, Lond. 1967, 1.
A.
215,
526.
10 to 4 for
streptomycin,
30 to 4 for
kanamycin, and
17 to 4 for
cycloserine. solid medium were also done. Acridines, especially proflavine, increased the bactericidal activity of antituberculosis drugs. Thus after 30 days’ incubation at 37°C, isoniazid was bactericidal in concentrations of not less than 25 g. per ml., and in concentrations of 0-75 {jLg. per ml. when proflavine was added. The corresponding concentrations for streptomycin were 2 and 0-25 g. per ml., and for cycloserine more than 50 and 12-5 g. per ml. Viable
The
counts on
enhancing
effect of acridines may be of
importance in
treating tuberculous foci containing large numbers of M. tuberculosis. Department of Chemotherapy, Institute of Pharmacology and Chemotherapy, Academy of Medical Science of the U.S.S.R.
V. N. SOLOVIEV V. S. ZUEVA.
PLATELET-FACTOR-3 AVAILABILITY IN A PATIENT WITH GLANZMANN’S DISEASE SIR,-In some patients with Glanzmann’s disease (thrombocytasthenia), the prothrombin is not sufficiently consumed,12z when the platelet-rich plasma (P.R.P.) is incubated with kaolin, platelet factor 3 (P.F.3) activity is abnormal,1-4 On the other hand, when washed platelets are later assayed by the thrombo-
plastin-generation test (T.G.T.), normal platelet clotting activity is observed.23 Hardisty et al.l reported that the platelets of one of their patients were less active than normal ones when assayed by the T.G.T. Weiss and Kochwa 4 recorded that when this method was used on 1 % suspensions of the platelets of three of their patients the activity was normal, and that it was only when more diluted suspensions were used that the activity was lower than that observed in normal subjects. We have recently conducted a number of tests on the platelets of a patient with Glanzmann’s disease for the purpose of determining P.F.3 activity. The P.R.P. of the patient and of the controls were so adjusted with their own platelet-poor plasmas (P.P.P.) as to contain 200,000 platelets per c.mm. The P.R.P. was centrifuged at 4500 r.p.m. for 30 minutes at 5°C. The supernatant was discarded; the platelet pellets were resuspended successively in substrate P.P.P., in isotonic saline solution, and in distilled water, retaining the original volume. The platelet suspensions made in saline and in distilled water were mixed with an equal volume of substrate P.P.P. The’Stypven’time for the P.P.P. treated in this way was then recorded. One of the tests was carried out after the platelets had been washed in a saline solution three times. The results were as follows (stypven-time in seconds):
These findings clearly show that in this patient the amount of P.P.3 activity made available was less than in normal subjects. The more the platelets were manipulated, the more active they became. When incubated in distilled water the coagulant activity became normal. This indicates that, as in thrombopathia (Willebrand-Jurgens type), the platelets contain this factor but it does not easily become available. In the T.G.T. assay, a 200,000 per c.mm. platelet suspension showed that the minimum substrate clotting time was 3 seconds longer with the patient’s platelets than with those of normal subjects. Kaolin did not have any effect on the patient’s P.R.P. stypventime. Department of Hæmatology, ŞEREF INCEMAN 1st Internal Clinic of Istanbul Medical School, YÜCEL TANGÜN. Istanbul, Turkey. R. M., Dormandy, K. M., Hutton, R. A. Br. J. Hœmat. 1964, 10, 371. 2. Zucker, M. B., Pert, J., Hilgartner, M. W. Blood, 1966, 28, 524. 3. Caen, J. P., Castaldi, P. A., Leclerc, J. C., Inceman, Ş., Larrieu, M. J. Probst, M., Bernard, J. Am. J. Med. 1966, 41, 4. 4. Weiss, H. J., Kochwa, S. J. Lab. clin. med. 1968, 71, 163. 1.
Hardisty,
precipitating factor: hypertension (2 patients), diabetes mellitus (1), systemic lupus erythematosus (1), and myxredema (1). The 6th patient has a diaphragmatic hernia; an E.C.G. during her stay in hospital showed only T-wave changes, which subsided after a few days, so that it is not clear whether they due to coronary heart-disease. No data are available about the 7th patient. These findings show that myocardial infarction without a precipitating factor is uncommon in women during their productive period. J. SCHARF A. M. NAHIR Department of Internal Medicine A, B. PELED Rambam Government Hospital. A. ASAD. Haifa, Israel.
were
A MAMMO-RENAL SYNDROME ? SIR,-One of my female patients was operated on for bilateral Routine pyelography showed breasts. supernumerary bilateral supernumerary kidneys, with ureters entering independently into the bladder.Another female patient had a unilateral supernumerary breast. Pyelography showed a supernumerary kidney on the same side, ending in a common ureter. Anomalies associated with supernumerary breasts have not been reported. In females, prevalence of supenumerary breasts is about 1 % and the prevalence of kidney reduplication is equally about 1 %. The chance occurrence of the two anomalies in the same patient is 1 in 10,000. I wonder whether aplasia of one breast is not associated -with unilateral renal hypoplasia in some rare instances. Ter Weeden-Zulte, LUC GOEMINNE. Belgium.
ENHANCEMENT OF ANTITUBERCULOSIS-DRUG ACTION BY ACRIDINES
SiR,-Sevag et al.23 have shown that mepacrine (’ Atabrine ’) and other acridines inhibit the development of drug resistance by Staphylococcus spp. and Escherichia coli during continuous incubation in a liquid medium. Lately Warren et al.4 have reported that mepacrine also inhibits development of drug resistance by Mycobacterium tuberculosis. Several acridines have been studied in our laboratory, and several compounds have shown much higher activity than mepacrine. They also inhibit the development of resistance to streptomycin in M. phlei and M. avium. We report here preliminary findings on the influence of acridines on the activity of antituberculosis
drugs. M. tuberculosis, strain H37Rv, was suspended in Sauton medium enriched with bovine serum andTween 80’. Non-bacteriostatic concentrations of acridines were established in preliminary experiments. The activity of antituberculosis drugs was tested by serial dilution in the same medium. The viable count of mycobacteria in each tube was about 2 x 108. Such a large population must have contained resistant mutants, thus increasing the minimal inhibiting concentration (M.l.C.) of the drug. The M.i.c. of each drug (in g. per ml.) greatly diminished when one of the acridines in sub-bacteriostatic concentrations was added, as follows:
The coefficients of activation
were
1250
to
20 for
isoniazid,
(editor) Handbook of Congenital Malformations; p. 17. Rubin, Philadelphia. 1967 2. Sevag, M. G., Ashton, B. Nature, Lond. 1964, 203, 1323-1326. 3. Heller, C. S., Sevag, M. G. Appl. Microbiol. 1966, 14, 879. 4. Warren, G., Gregory, F., Healy, E., Flint, S. Nature, Lond. 1967, 1.
A.
215,
526.
10 to 4 for
streptomycin,
30 to 4 for
kanamycin, and
17 to 4 for
cycloserine. solid medium were also done. Acridines, especially proflavine, increased the bactericidal activity of antituberculosis drugs. Thus after 30 days’ incubation at 37°C, isoniazid was bactericidal in concentrations of not less than 25 g. per ml., and in concentrations of 0-75 {jLg. per ml. when proflavine was added. The corresponding concentrations for streptomycin were 2 and 0-25 g. per ml., and for cycloserine more than 50 and 12-5 g. per ml. Viable
The
counts on
enhancing
effect of acridines may be of
importance in
treating tuberculous foci containing large numbers of M. tuberculosis. Department of Chemotherapy, Institute of Pharmacology and Chemotherapy, Academy of Medical Science of the U.S.S.R.
V. N. SOLOVIEV V. S. ZUEVA.
PLATELET-FACTOR-3 AVAILABILITY IN A PATIENT WITH GLANZMANN’S DISEASE SIR,-In some patients with Glanzmann’s disease (thrombocytasthenia), the prothrombin is not sufficiently consumed,12z when the platelet-rich plasma (P.R.P.) is incubated with kaolin, platelet factor 3 (P.F.3) activity is abnormal,1-4 On the other hand, when washed platelets are later assayed by the thrombo-
plastin-generation test (T.G.T.), normal platelet clotting activity is observed.23 Hardisty et al.l reported that the platelets of one of their patients were less active than normal ones when assayed by the T.G.T. Weiss and Kochwa 4 recorded that when this method was used on 1 % suspensions of the platelets of three of their patients the activity was normal, and that it was only when more diluted suspensions were used that the activity was lower than that observed in normal subjects. We have recently conducted a number of tests on the platelets of a patient with Glanzmann’s disease for the purpose of determining P.F.3 activity. The P.R.P. of the patient and of the controls were so adjusted with their own platelet-poor plasmas (P.P.P.) as to contain 200,000 platelets per c.mm. The P.R.P. was centrifuged at 4500 r.p.m. for 30 minutes at 5°C. The supernatant was discarded; the platelet pellets were resuspended successively in substrate P.P.P., in isotonic saline solution, and in distilled water, retaining the original volume. The platelet suspensions made in saline and in distilled water were mixed with an equal volume of substrate P.P.P. The’Stypven’time for the P.P.P. treated in this way was then recorded. One of the tests was carried out after the platelets had been washed in a saline solution three times. The results were as follows (stypven-time in seconds):
These findings clearly show that in this patient the amount of P.P.3 activity made available was less than in normal subjects. The more the platelets were manipulated, the more active they became. When incubated in distilled water the coagulant activity became normal. This indicates that, as in thrombopathia (Willebrand-Jurgens type), the platelets contain this factor but it does not easily become available. In the T.G.T. assay, a 200,000 per c.mm. platelet suspension showed that the minimum substrate clotting time was 3 seconds longer with the patient’s platelets than with those of normal subjects. Kaolin did not have any effect on the patient’s P.R.P. stypventime. Department of Hæmatology, ŞEREF INCEMAN 1st Internal Clinic of Istanbul Medical School, YÜCEL TANGÜN. Istanbul, Turkey. R. M., Dormandy, K. M., Hutton, R. A. Br. J. Hœmat. 1964, 10, 371. 2. Zucker, M. B., Pert, J., Hilgartner, M. W. Blood, 1966, 28, 524. 3. Caen, J. P., Castaldi, P. A., Leclerc, J. C., Inceman, Ş., Larrieu, M. J. Probst, M., Bernard, J. Am. J. Med. 1966, 41, 4. 4. Weiss, H. J., Kochwa, S. J. Lab. clin. med. 1968, 71, 163. 1.
Hardisty,