367 TKBLE
JI-6-{)H-F AND 17-oHc.s.
EXCRETED IN
24 h URINE
IN PATIENT
441TH PULMONARY TUBERCULOSIS RECEIVING RIFAMPICIN
g/24 h 17-OHc.s.3.5-6.0 mg/24 h This 67-year-old man was given 450 mg rifampicin, 0.4 g isoniazid, and 0.5 g tKptomycm daily. The 24 h urine was collected on a day when rifampicin ’,tas yen and on another day when the drug was not given. The collections of ,4 h unne were repeated 3 weeks later (lower set of data).
Bormal ranges: 6-OH-F 200-500
duced or inhibited
activity of the liver microsomal cortisol-6hydroxylase by drugs was easily detected, because the time required for the collection of the urine was shortened and the volume of the urine decreased to permit the routine determination of urinary 6-OH-F as an index of the liver hydroxylase activity. In all of the patients receiving 450 mg of rifampicin and 0.4 g of isoniazid daily, urinary 6-OH-F excretion increased strikingly despite the isoniazid (table i). Raisfeld et a1.4 have reported that cytochrome P-450 in the rat liver was reduced remarkably after isoniazid was given. In our study, the patients maintained with isoniazid and/or p-aminosalicylic acid showed decreased levels of urinary 6-OH-F excretion (table I), indicating the inhibitory effect of isoniazid and p-aminosalicylic acid on the liver cortisol-6-hydroxylase activity. A 25-year-old healthy female who had received no drugs for more than 2 weeks was, with her informed consent, given 300 mg of rifampicin every other day for a total of three doses. The excretions of 6-OH-F before administration, on the following day, and on 6th day after the last administration of the drug were measured. Urinary 6-OH-F excretion increased remarkably from 228 to 1271 g/3 h on the day after the last administration of the drug and returned to normal (396) on 6th day after rifampicin was stopped. Four epileptic patients receiving 100 mg of phenytoin and 200 mg of mephobarbitone per day
this in my practice. Obviously facilities for a controlled trial have not yet been possible, but I wish to report that the first five patients with acne to whom the drug has been given have all improved. Two of these patients had previously been on tetracycline, and metronidazole has so far given superior results. Again, one must stress that the treatment of acne will ’. have to be considered on a long-term basis. The Grove Health Centre, Goldhawk Road, London W12
8EJ
STUART CARNE
SIMPLIFIED LABORATORY TEST FOR MULTIPLE SCLEROSIS
SiR,—The macrophage electrophoretic mobility (M.E.M.) for multiple sclerosis (M.S.) described by Field et al.1 and confirmed by Jenssen et al. and Meyer-Rienecker et al.3 demands great attention to detail and has not met with success in the hands of another group.4 Determination of the absolute mobility of erythrocytes on the other hand is a long-established technique, though it, too, has its difficulties and calls for considerable care.s With a Zeiss microelectrophoresis apparatus (cytopherometer) and an LKB conductolyser for measurement of specific resistance we have determined the absolute mobility of red blood-cells in medium 199 (Hanks based, Bio-Cult) alone and in the presence of linoleic acid (L.A.), oleic acid (O.A.), or arachidonic acid (A.A.). Red blood-cells were prepared by defibrination of sterile blood with glass beads. 1-5ml of defibrinated blood were test
% CHANGE
IN ABSOLUTE MOBILITY IN PATIENTS WITH M.S. AND O.N.D. AND IN CONTROLS
excreted increased levels of 6-OH-F in 3 h urine after administration of 20 mg of cortisol, values being 901, 987, 892, and 1053 3 h. Rifampicin and these anticonvulsants caused nearly the same degree of induction of the liver cortisol-6-hyd-
roxylase activity. A patient with pulmonary tuberculosis receiving 450 mg of rifampicin and 0.4 g of isoniazid every day showed an increased 6-OH-F excretion in 24 h urine without administration of cortisol (table n). The levels of 6-OH-F in 24 h urine were higher on the day when rifampicin was not given than on the day when the drug was given. There might be some competition between cortisol and rifampicin for the hydroxylating enzyme when rifampicin was given. Urinary 17-OHc.s. in 24 h urine were increased coincidentally in the same patient without administration of cortisol, but his urinary 17-hydroxycorticosteroids in 3 h urine after administration of 20 mg of cortisol remained within the normal range (2.9 mg/3 h). It seems likely that the clinical amelioration of Cushing’s syndrome will be attained by the intermittent administration of rifampicin (e.g., twice a week). Second Division, Department of Internal Medicine, School of Medicine, Kyoto University, Kyoto, Japan
SATOSHI YAMADA KAZUYOSHI IWAI
of absolute mobility were within 4% of the absolute value. In every case control v. L.A. and control v. A.A., p
JI-6-{)H-F AND 17-oHc.s.
EXCRETED IN
24 h URINE
IN PATIENT
441TH PULMONARY TUBERCULOSIS RECEIVING RIFAMPICIN
g/24 h 17-OHc.s.3.5-6.0 mg/24 h This 67-year-old man was given 450 mg rifampicin, 0.4 g isoniazid, and 0.5 g tKptomycm daily. The 24 h urine was collected on a day when rifampicin ’,tas yen and on another day when the drug was not given. The collections of ,4 h unne were repeated 3 weeks later (lower set of data).
Bormal ranges: 6-OH-F 200-500
duced or inhibited
activity of the liver microsomal cortisol-6hydroxylase by drugs was easily detected, because the time required for the collection of the urine was shortened and the volume of the urine decreased to permit the routine determination of urinary 6-OH-F as an index of the liver hydroxylase activity. In all of the patients receiving 450 mg of rifampicin and 0.4 g of isoniazid daily, urinary 6-OH-F excretion increased strikingly despite the isoniazid (table i). Raisfeld et a1.4 have reported that cytochrome P-450 in the rat liver was reduced remarkably after isoniazid was given. In our study, the patients maintained with isoniazid and/or p-aminosalicylic acid showed decreased levels of urinary 6-OH-F excretion (table I), indicating the inhibitory effect of isoniazid and p-aminosalicylic acid on the liver cortisol-6-hydroxylase activity. A 25-year-old healthy female who had received no drugs for more than 2 weeks was, with her informed consent, given 300 mg of rifampicin every other day for a total of three doses. The excretions of 6-OH-F before administration, on the following day, and on 6th day after the last administration of the drug were measured. Urinary 6-OH-F excretion increased remarkably from 228 to 1271 g/3 h on the day after the last administration of the drug and returned to normal (396) on 6th day after rifampicin was stopped. Four epileptic patients receiving 100 mg of phenytoin and 200 mg of mephobarbitone per day
this in my practice. Obviously facilities for a controlled trial have not yet been possible, but I wish to report that the first five patients with acne to whom the drug has been given have all improved. Two of these patients had previously been on tetracycline, and metronidazole has so far given superior results. Again, one must stress that the treatment of acne will ’. have to be considered on a long-term basis. The Grove Health Centre, Goldhawk Road, London W12
8EJ
STUART CARNE
SIMPLIFIED LABORATORY TEST FOR MULTIPLE SCLEROSIS
SiR,—The macrophage electrophoretic mobility (M.E.M.) for multiple sclerosis (M.S.) described by Field et al.1 and confirmed by Jenssen et al. and Meyer-Rienecker et al.3 demands great attention to detail and has not met with success in the hands of another group.4 Determination of the absolute mobility of erythrocytes on the other hand is a long-established technique, though it, too, has its difficulties and calls for considerable care.s With a Zeiss microelectrophoresis apparatus (cytopherometer) and an LKB conductolyser for measurement of specific resistance we have determined the absolute mobility of red blood-cells in medium 199 (Hanks based, Bio-Cult) alone and in the presence of linoleic acid (L.A.), oleic acid (O.A.), or arachidonic acid (A.A.). Red blood-cells were prepared by defibrination of sterile blood with glass beads. 1-5ml of defibrinated blood were test
% CHANGE
IN ABSOLUTE MOBILITY IN PATIENTS WITH M.S. AND O.N.D. AND IN CONTROLS
excreted increased levels of 6-OH-F in 3 h urine after administration of 20 mg of cortisol, values being 901, 987, 892, and 1053 3 h. Rifampicin and these anticonvulsants caused nearly the same degree of induction of the liver cortisol-6-hyd-
roxylase activity. A patient with pulmonary tuberculosis receiving 450 mg of rifampicin and 0.4 g of isoniazid every day showed an increased 6-OH-F excretion in 24 h urine without administration of cortisol (table n). The levels of 6-OH-F in 24 h urine were higher on the day when rifampicin was not given than on the day when the drug was given. There might be some competition between cortisol and rifampicin for the hydroxylating enzyme when rifampicin was given. Urinary 17-OHc.s. in 24 h urine were increased coincidentally in the same patient without administration of cortisol, but his urinary 17-hydroxycorticosteroids in 3 h urine after administration of 20 mg of cortisol remained within the normal range (2.9 mg/3 h). It seems likely that the clinical amelioration of Cushing’s syndrome will be attained by the intermittent administration of rifampicin (e.g., twice a week). Second Division, Department of Internal Medicine, School of Medicine, Kyoto University, Kyoto, Japan
SATOSHI YAMADA KAZUYOSHI IWAI
of absolute mobility were within 4% of the absolute value. In every case control v. L.A. and control v. A.A., p
