- Email: [email protected]
URIC ACID IN BONE-MARROW
532 To
our
treatment
knowledge this is the first case in which prophylactic of endogenous depression with tryptophan has been
tried. We wish to thank Hoffmann-La
Roche, Basle, for supplying the
tryptophan. Department of Psychiatry, Rothschild-Hadassah University Hospital,
D. HERTZ.
Jerusalem. Department of Applied Pharmacology, School of Pharmacy, Hebrew University, Jerusalem.
F. G. SULMAN.
URIC ACID IN BONE-MARROW urates in gout can invade medullary spaces of bone as well as subchondral areas, joint capsules, ligaments, tendons, and bursse usually adjacent to demonstrable tophi. We have not been able to find in standard textbooks or published reports other mention of urates in the medullary spaces. The appearance of typical uric-acid crystals in the sternal bone-marrow of an anxmic patient prompts us to give here a brief resume of her case. A 64-year old White woman was admitted to this hospital for investigation of fever and anaemia. Some 10 years before she had been treated for rheumatoid arthritis with prednisone, 10 mg., and phenylbutazone, 200 mg., daily with control of symptoms. 10 years before that she had received multiple blood-transfusion and had had a subtotal gastrectomy for a bleeding gastric ulcer. She claimed to have had brief, brightred, rectal bleeding a month before admission, and was taking chlorthalidone for mild systolic hypertension. The patient showed pallor and listlessness, bilateral knee effusion, and fusiform swelling and tophageous enlargement of
SiR,-Talbott has stated that
uric-acid to 67 mg. per 100 ml. The hsematocrit rose to normal levels after six months’ therapy. The patient’s clinical appearance and past history were consistent with gout. The degree to which coincident therapy with chlorthalidone may have raised the serum-uric-acid level is unknown, since probenecid was given at the same time as the diuretic was discontinued. Iron-deficiency ansemia was diagnosed by history, the appearance of the peripheral blood, and the serum-iron. The estimation of bone-marrow iron as normal to reduced can perhaps be explained by the unavailability of iron derived from previous blood-transfusions.2 Whether the uric acid in this patient’s bone-marrow has any significance in the development of an2emia is unknown, since there is no reported relation between the two. It would be interesting to know whether uric acid can be found in the bonemarrows of other gouty patients. We are indebted to Dr. Ronald S. Beckett, department of patho-
logy, Hartford Hospital, for
his assistance.
Department of Medicine, Hartford Hospital, Hartford, Connecticut 06115.
WILLIAM C. HARVEY EDWARD SCULL.
HYPOTENSION AFTER ORAL PROPRANOLOL SIR,-Dr. Bett’s letter (Feb. 10, p. 302) prompts me to report the following case. A 50-year-old man with a history of cardiomyopathy, congestive heart-failure, and frequent atrial arrhythmias which had
required several cardioversions, was given 10 mg. of propranolol orally at home in December, 1967. Within half an hour he developed severe epigastric pain and diarrhoea, and became profoundly collapsed. He was admitted to hospital and made a good recovery with the use of isoprenaline (’ Isuprel’), minute, over 24 hours. In view of the severity of his arrhythmias, the patient was readmitted soon afterwards to the intensive-care unit for a carefully controlled trial of small doses of propranolol. His ventricular rate was 140 per minute. 2-5 mg. of propranolol was given at 9 A.M. and 10 A.M. without effect except for a soft bowel movement. At 11 A.M. 5 mg. was given and soon afterwards he complained of epigastric pain and had another bowel movement. The pain subsided over the next 2 hours and, since there was no change in blood-pressure (B.P.) or heart-rate, a further 5 mg. was given at 2 P.M. 30 minutes later he again complained of epigastric pain, and became somewhat cyanosed, and his heart-rate fell to 115 per minute. At 4 P.M. circulatory collapse suddenly ensued, with hypotension, intense sweating, cyanosis, tachypnoea, and disorientation. Isoprenaline, 4 (Lg. per minute, was started at once with little effect. At 4.40 P.M. cardioversion was performed with reversion to sinus rhythm. At 5 P.M. the systolic B.P. was 130 mm. Hg, venous pH 7-18, serum-amylase 108 units, serum-bilirubin 4 mg. per 100 ml., blood-glucose 54 mg. per 100 ml., and white blood-cells
up to 10 {jt.g. per
Unstained
smear
of bone-marrow
showing birefringent needle-
shaped crystals of uric acid. Reduced to half from x 700.
15,200 (67% polymorphs) per c.mm. Isoprenaline was increased 15 g. per minute, and he was given 170 meq. of sodium bicarbonate over the next 3 hours, with a presumptive diagnosis to
the distal and proximal interphalangeal joints of both hands. The haematocrit was 23% and a smear of the peripheral blood showed anisocytosis and poikilocytosis with pronounced hypochromia. Serum-iron was 5 g. per 100 ml. with a binding capacity of 336 g. per 100 ml. (1-5% saturation). The serum-uric-acid was 10-0 mg. per 100 ml. The bone-marrow elements were morphologically normal and erythroid activity was decreased. Marrow-ion was estimated as " normal to reduced ". The bone-marrow aspirate also showed birefringent needle-shaped crystals, seen in both unstained smears (see accompanying figure) and in those prepared with Wright’s stain, with the appearance of uric acid. There was no evidence of surrounding inflammatory reaction or gouty changes. Chronic tophaceous gout was diagnosed and the patient was started on colchicine, 0-5 mg. three times daily, with improvement in joint-pain, and oral iron. Allopurinol, 100 mg. three times daily, was later given with resultant decrease in serum1.
Talbott, J.
H.
Gout, p. 76.
New
York, 1964.
of lactic acidosis. The patient gradually improved and was back to his normal state by late evening. Isoprenaline was required in decreasing doses for 70 hours in view of a central venous pressure persistently over 30 cm. of water. The next morning the serumglutamic-oxaloacetic-transaminase (S.G.O.T.) was 626 units, serum-amylase 324 units, serum-bilirubin 3 mg. per 100 ml., white blood-cells 14,300 per c.mm. (83% polymorphs). 24 hours later s.G.o.T. was 650 units, serum-amylase 280 units, serum-bilirubin 2-2 mg. per 100 ml., and serum-creatinephosphokinase normal, and 48 hours later S.G.O.T. was 480 units, and serum-amylase 200 units. The following lessons may be drawn from this episode: in patients with severe heart-disease, it is advisable to give the first doses of propranolol in hospital; propranolol in small oral doses may cause profound shock and pancreatitis in susceptible Fairbanks, V., Fahey, J. Clinical Disorders of Iron Metabolism; p. 100. New York, 1963.
2. Beutler, E.,
our
treatment
knowledge this is the first case in which prophylactic of endogenous depression with tryptophan has been
tried. We wish to thank Hoffmann-La
Roche, Basle, for supplying the
tryptophan. Department of Psychiatry, Rothschild-Hadassah University Hospital,
D. HERTZ.
Jerusalem. Department of Applied Pharmacology, School of Pharmacy, Hebrew University, Jerusalem.
F. G. SULMAN.
URIC ACID IN BONE-MARROW urates in gout can invade medullary spaces of bone as well as subchondral areas, joint capsules, ligaments, tendons, and bursse usually adjacent to demonstrable tophi. We have not been able to find in standard textbooks or published reports other mention of urates in the medullary spaces. The appearance of typical uric-acid crystals in the sternal bone-marrow of an anxmic patient prompts us to give here a brief resume of her case. A 64-year old White woman was admitted to this hospital for investigation of fever and anaemia. Some 10 years before she had been treated for rheumatoid arthritis with prednisone, 10 mg., and phenylbutazone, 200 mg., daily with control of symptoms. 10 years before that she had received multiple blood-transfusion and had had a subtotal gastrectomy for a bleeding gastric ulcer. She claimed to have had brief, brightred, rectal bleeding a month before admission, and was taking chlorthalidone for mild systolic hypertension. The patient showed pallor and listlessness, bilateral knee effusion, and fusiform swelling and tophageous enlargement of
SiR,-Talbott has stated that
uric-acid to 67 mg. per 100 ml. The hsematocrit rose to normal levels after six months’ therapy. The patient’s clinical appearance and past history were consistent with gout. The degree to which coincident therapy with chlorthalidone may have raised the serum-uric-acid level is unknown, since probenecid was given at the same time as the diuretic was discontinued. Iron-deficiency ansemia was diagnosed by history, the appearance of the peripheral blood, and the serum-iron. The estimation of bone-marrow iron as normal to reduced can perhaps be explained by the unavailability of iron derived from previous blood-transfusions.2 Whether the uric acid in this patient’s bone-marrow has any significance in the development of an2emia is unknown, since there is no reported relation between the two. It would be interesting to know whether uric acid can be found in the bonemarrows of other gouty patients. We are indebted to Dr. Ronald S. Beckett, department of patho-
logy, Hartford Hospital, for
his assistance.
Department of Medicine, Hartford Hospital, Hartford, Connecticut 06115.
WILLIAM C. HARVEY EDWARD SCULL.
HYPOTENSION AFTER ORAL PROPRANOLOL SIR,-Dr. Bett’s letter (Feb. 10, p. 302) prompts me to report the following case. A 50-year-old man with a history of cardiomyopathy, congestive heart-failure, and frequent atrial arrhythmias which had
required several cardioversions, was given 10 mg. of propranolol orally at home in December, 1967. Within half an hour he developed severe epigastric pain and diarrhoea, and became profoundly collapsed. He was admitted to hospital and made a good recovery with the use of isoprenaline (’ Isuprel’), minute, over 24 hours. In view of the severity of his arrhythmias, the patient was readmitted soon afterwards to the intensive-care unit for a carefully controlled trial of small doses of propranolol. His ventricular rate was 140 per minute. 2-5 mg. of propranolol was given at 9 A.M. and 10 A.M. without effect except for a soft bowel movement. At 11 A.M. 5 mg. was given and soon afterwards he complained of epigastric pain and had another bowel movement. The pain subsided over the next 2 hours and, since there was no change in blood-pressure (B.P.) or heart-rate, a further 5 mg. was given at 2 P.M. 30 minutes later he again complained of epigastric pain, and became somewhat cyanosed, and his heart-rate fell to 115 per minute. At 4 P.M. circulatory collapse suddenly ensued, with hypotension, intense sweating, cyanosis, tachypnoea, and disorientation. Isoprenaline, 4 (Lg. per minute, was started at once with little effect. At 4.40 P.M. cardioversion was performed with reversion to sinus rhythm. At 5 P.M. the systolic B.P. was 130 mm. Hg, venous pH 7-18, serum-amylase 108 units, serum-bilirubin 4 mg. per 100 ml., blood-glucose 54 mg. per 100 ml., and white blood-cells
up to 10 {jt.g. per
Unstained
smear
of bone-marrow
showing birefringent needle-
shaped crystals of uric acid. Reduced to half from x 700.
15,200 (67% polymorphs) per c.mm. Isoprenaline was increased 15 g. per minute, and he was given 170 meq. of sodium bicarbonate over the next 3 hours, with a presumptive diagnosis to
the distal and proximal interphalangeal joints of both hands. The haematocrit was 23% and a smear of the peripheral blood showed anisocytosis and poikilocytosis with pronounced hypochromia. Serum-iron was 5 g. per 100 ml. with a binding capacity of 336 g. per 100 ml. (1-5% saturation). The serum-uric-acid was 10-0 mg. per 100 ml. The bone-marrow elements were morphologically normal and erythroid activity was decreased. Marrow-ion was estimated as " normal to reduced ". The bone-marrow aspirate also showed birefringent needle-shaped crystals, seen in both unstained smears (see accompanying figure) and in those prepared with Wright’s stain, with the appearance of uric acid. There was no evidence of surrounding inflammatory reaction or gouty changes. Chronic tophaceous gout was diagnosed and the patient was started on colchicine, 0-5 mg. three times daily, with improvement in joint-pain, and oral iron. Allopurinol, 100 mg. three times daily, was later given with resultant decrease in serum1.
Talbott, J.
H.
Gout, p. 76.
New
York, 1964.
of lactic acidosis. The patient gradually improved and was back to his normal state by late evening. Isoprenaline was required in decreasing doses for 70 hours in view of a central venous pressure persistently over 30 cm. of water. The next morning the serumglutamic-oxaloacetic-transaminase (S.G.O.T.) was 626 units, serum-amylase 324 units, serum-bilirubin 3 mg. per 100 ml., white blood-cells 14,300 per c.mm. (83% polymorphs). 24 hours later s.G.o.T. was 650 units, serum-amylase 280 units, serum-bilirubin 2-2 mg. per 100 ml., and serum-creatinephosphokinase normal, and 48 hours later S.G.O.T. was 480 units, and serum-amylase 200 units. The following lessons may be drawn from this episode: in patients with severe heart-disease, it is advisable to give the first doses of propranolol in hospital; propranolol in small oral doses may cause profound shock and pancreatitis in susceptible Fairbanks, V., Fahey, J. Clinical Disorders of Iron Metabolism; p. 100. New York, 1963.
2. Beutler, E.,