- Email: [email protected]
ETHACRYNIC ACID IN ACUTE RENAL FAILURE
1255
periosteum
with radio-opaque shadows around the knee-joints and cervical region; these features were absent later. The youngest child shows haziness of periosteum of forearm
recent studies-one by Thurau indicating that the sodium content of the macula densa regulates afferent arteriolar flow and the other by Birtch et al.2 showing that ethacrynic acid
bones.
at the expense of medullary physiological explanation for our findings. They are reported here in the expectation that others might give this therapy a trial.
increases renal cortical flow
Tyrosine crystals in bone-marrow and changes reports
the radiological noted above have not been described in any previous
on
tyrosinosis
or
tyrosinsemia.
blood-flow-both
We should like to express our thanks to Dr. A. Mokadam, medical superintendent, and Dr. M. K. Khandelwal, in charge of the paediatric department, Daga Memorial Hospital, for clinical facilities, and to Prof. M. C. Nath, head of the department of biochemistry, University of Nagpur, for biochemical investigations and guidance. Department of Pædiatrics, Daga Memorial Hospital for Women and Children, Nagpur, India.
Department of Biochemistry, Nagpur University.
R. B. JAISWAL. IDREES BHAI N. NATH.
ETHACRYNIC ACID IN ACUTE RENAL FAILURE SIR,-We should like to draw attention to the possible value of intravenous ethacrynic acid for patients with incipient acute renal failure. We have used this almost routinely now foi three years when, after adequate fluid replacement, often including mannitol infusion, the patient remains oliguric. Three different responses have been encountered. In the first, bloodpressure is low, peripheral circulation poor, and the response to ethacrynic acid usually negligible. In the second group, urine output shows a marked immediate increase which may persist or return to the previous level. In the former, the urine volume may be maintained in excess of 60 ml. per hour yet the creatinine clearance remains low (less than 10 ml. per minute). In this instance, oliguric renal failure has been converted to the non-oliguric form which no longer requires rigid fluid and electrolyte restriction. The third group have a brisk diuretic response and resume normal renal function. They represent perhaps 5% of the total. The following case illustrates this type of response:e admitted to hospital at 9 A.M. on confused state without any previous medical history. She was in shock; peripheral circulation was very poor, blood-pressure unobtainable, and pulse 120 and regular. She was catheterised and found to be anuric. Electrocardiography confirmed the diagnosis of recent myocardial infarction. She remained anuric until she received ethacrynic acid (see accompanying table) and thereafter continued to have adequate renal function. A
77-year-old
Jan. 22, 1968, in
woman was
a
If these results are accepted as a definite modification of the course of ischasmic acute renal failure (and we think they are), then the mechanism by which the drug acts could be important in understanding the pathogenesis of this syndrome. Two
Division of Nephrology, Montreal General Hospital, Montreal 25, Quebec, Canada.
All
a
MICHAEL KAYE LOUIS DUFRESNE DOROTHY MCDADE.
CULTIVATING LEUKÆMIC LYMPHOCYTES SIR,-We were interested to read the description by Dr. Moore and his colleagues (Feb. 17, p. 363) of a successful modification for obtaining chromosome spreads of patients with chronic lymphatic leukxmia. They used leukaemia lymphocytes from peripheral blood and cultivated them for only 48 hours at 38°C in the following culture medium: NCTC-109 69%, foetal calf serum 30%, and antibiotics 1 %. Their findings prompted me to outline my experience. The defective reaction to phytohasmagglutinin (P.H.A.) reported by many workers3 has been overcome in our laboratory by one-fold passage of the culture after 72 hours on the same medium of synthetic Parker 199 medium 70% and calf serum 30 %, without further supplementation ofp.H.A. The percentage of blast cells present on the 6th day of cultivation was, in six patients, 29 (7-5-80-7) and the mitotic index was 4-1 (0-3-15-8). It was interesting to see such a dramatic rise in blast-cell count simply after the change of culture medium. Our culture technique is, briefly, as follows: lymphocyte suspensions obtained by sedimentation of heparinised blood are transferred to culture flasks containing medium TC 199 70% and complement-free calf serum 30%. P.H.A. P (Difco) is added-0-025 ml. of the commercial solution per 10 ml. of culture fluid. The lymphocytes are cultured at 37°C diluted in the nutrient medium to the concentration of 106 per ml. The passage on the fourth day is accomplished quickly and no P.H.A. is added. The cultures are harvested on the sixth day after incubation with demecolcine 0.2 g. per ml. for 2 hours. The transformation and mitotic process are evaluated by a count of 1000 cells in May-Grunwald-Giemsa stained smears and also on the air-dried preparations stained with Giemsa. Very probably the metabolic requirements of leukxmic cells are different from normal cells, and this fact is reflected by the 1. 2.
3.
Thurau, K. Int. Cong. Nephrol. 1966, 1, 162. Birtch, A. G. Zakheim, R. M., Jones, L. G., Barger, A. C. Circulation Res. 1967, 21, 869. Trubowitz, S., Masek, B., Del Rosario, A. Cancer, N.Y. 1966, 19, 2019. Pössnerova, V., Hermansky, F. Neoplasma, 1966, 13, 417. Elves, M. W., Collinge, M., Israëls, M. C. G. Acta hœmat. 1967, 37, 100.
CLINICAL AND BIOCHEMICAL DATA
*
suggest
therapy given intravenously.
periosteum
with radio-opaque shadows around the knee-joints and cervical region; these features were absent later. The youngest child shows haziness of periosteum of forearm
recent studies-one by Thurau indicating that the sodium content of the macula densa regulates afferent arteriolar flow and the other by Birtch et al.2 showing that ethacrynic acid
bones.
at the expense of medullary physiological explanation for our findings. They are reported here in the expectation that others might give this therapy a trial.
increases renal cortical flow
Tyrosine crystals in bone-marrow and changes reports
the radiological noted above have not been described in any previous
on
tyrosinosis
or
tyrosinsemia.
blood-flow-both
We should like to express our thanks to Dr. A. Mokadam, medical superintendent, and Dr. M. K. Khandelwal, in charge of the paediatric department, Daga Memorial Hospital, for clinical facilities, and to Prof. M. C. Nath, head of the department of biochemistry, University of Nagpur, for biochemical investigations and guidance. Department of Pædiatrics, Daga Memorial Hospital for Women and Children, Nagpur, India.
Department of Biochemistry, Nagpur University.
R. B. JAISWAL. IDREES BHAI N. NATH.
ETHACRYNIC ACID IN ACUTE RENAL FAILURE SIR,-We should like to draw attention to the possible value of intravenous ethacrynic acid for patients with incipient acute renal failure. We have used this almost routinely now foi three years when, after adequate fluid replacement, often including mannitol infusion, the patient remains oliguric. Three different responses have been encountered. In the first, bloodpressure is low, peripheral circulation poor, and the response to ethacrynic acid usually negligible. In the second group, urine output shows a marked immediate increase which may persist or return to the previous level. In the former, the urine volume may be maintained in excess of 60 ml. per hour yet the creatinine clearance remains low (less than 10 ml. per minute). In this instance, oliguric renal failure has been converted to the non-oliguric form which no longer requires rigid fluid and electrolyte restriction. The third group have a brisk diuretic response and resume normal renal function. They represent perhaps 5% of the total. The following case illustrates this type of response:e admitted to hospital at 9 A.M. on confused state without any previous medical history. She was in shock; peripheral circulation was very poor, blood-pressure unobtainable, and pulse 120 and regular. She was catheterised and found to be anuric. Electrocardiography confirmed the diagnosis of recent myocardial infarction. She remained anuric until she received ethacrynic acid (see accompanying table) and thereafter continued to have adequate renal function. A
77-year-old
Jan. 22, 1968, in
woman was
a
If these results are accepted as a definite modification of the course of ischasmic acute renal failure (and we think they are), then the mechanism by which the drug acts could be important in understanding the pathogenesis of this syndrome. Two
Division of Nephrology, Montreal General Hospital, Montreal 25, Quebec, Canada.
All
a
MICHAEL KAYE LOUIS DUFRESNE DOROTHY MCDADE.
CULTIVATING LEUKÆMIC LYMPHOCYTES SIR,-We were interested to read the description by Dr. Moore and his colleagues (Feb. 17, p. 363) of a successful modification for obtaining chromosome spreads of patients with chronic lymphatic leukxmia. They used leukaemia lymphocytes from peripheral blood and cultivated them for only 48 hours at 38°C in the following culture medium: NCTC-109 69%, foetal calf serum 30%, and antibiotics 1 %. Their findings prompted me to outline my experience. The defective reaction to phytohasmagglutinin (P.H.A.) reported by many workers3 has been overcome in our laboratory by one-fold passage of the culture after 72 hours on the same medium of synthetic Parker 199 medium 70% and calf serum 30 %, without further supplementation ofp.H.A. The percentage of blast cells present on the 6th day of cultivation was, in six patients, 29 (7-5-80-7) and the mitotic index was 4-1 (0-3-15-8). It was interesting to see such a dramatic rise in blast-cell count simply after the change of culture medium. Our culture technique is, briefly, as follows: lymphocyte suspensions obtained by sedimentation of heparinised blood are transferred to culture flasks containing medium TC 199 70% and complement-free calf serum 30%. P.H.A. P (Difco) is added-0-025 ml. of the commercial solution per 10 ml. of culture fluid. The lymphocytes are cultured at 37°C diluted in the nutrient medium to the concentration of 106 per ml. The passage on the fourth day is accomplished quickly and no P.H.A. is added. The cultures are harvested on the sixth day after incubation with demecolcine 0.2 g. per ml. for 2 hours. The transformation and mitotic process are evaluated by a count of 1000 cells in May-Grunwald-Giemsa stained smears and also on the air-dried preparations stained with Giemsa. Very probably the metabolic requirements of leukxmic cells are different from normal cells, and this fact is reflected by the 1. 2.
3.
Thurau, K. Int. Cong. Nephrol. 1966, 1, 162. Birtch, A. G. Zakheim, R. M., Jones, L. G., Barger, A. C. Circulation Res. 1967, 21, 869. Trubowitz, S., Masek, B., Del Rosario, A. Cancer, N.Y. 1966, 19, 2019. Pössnerova, V., Hermansky, F. Neoplasma, 1966, 13, 417. Elves, M. W., Collinge, M., Israëls, M. C. G. Acta hœmat. 1967, 37, 100.
CLINICAL AND BIOCHEMICAL DATA
*
suggest
therapy given intravenously.