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Reduction of hypertension in hypovolaemia
1454
absorbing surface, and any of the allergic rubber leachables (MET, raw latex, sulphites), appearing at random in rubber retention enema tips as a result of batch processing may cause allergic reactions when used for barium enema examinations. Lancet readers world wide should ask government regulatory bodies and manufacturers when natural rubber manufactured with MET was last used in unit-dose syringes and what are the expiry dates of the
drugs involved? 600 Colborne Street, London, Ontario N6B 2V2, Canada
GAVIN HAMILTON
Spaner D, Dolovich J, Tarlo S, Sussman G. Hypersensitivity to natural latex. J Allergy Clin Immunol 1989; 83: 1135-37. 2. Fisher AA. Management of dermatitis due to surgical gloves. J Dermatol Surg Oncol 1.
1985; 11: 628-31. 3. Hamilton G. Contamination of contrast agent by MBT in rubber seals. CMAJ 1987; 136: 1020-21. 4. Meek JH, Pettit BR. Avoidable accumulation of potentially toxic levels of benzothiazoles in babies receiving intravenous therapy. Lancet 1985; ii: 1090-92. 5. Graham DT, Mark, GE, Pomeroy AR. Chemical leaching from Terumo syringe seals. Aust NZ J Med 1982; 12: 305-06. 6. Bettmann MA. Ionic versus nonionic contrast agents for intravenous uses: are all the answers in? Radiology 1990; 175: 616-18. 7. Katayama H, Yamaguchi K, Kosuka T, Takashima T, Seez P, Matsuura T. Reactions to ionic and nonionic contrast media. Radiology 1990; 175: 621-28. 8. Napke E, Stevens DGH. Excipients and additives: hidden hazards in drug products and in product substitution. CMAJ 1984; 131: 1449-52. 9. Blais P. The impact of medical devices on quality of pharmaceuticals. In: Warbick-Cerone A, Johnston LG, eds. Quality assurance of pharmaceuticals manufactured in the hospitals. New York: Pergamon, 1985: 83-93.
Haematuria and proteinuria after
thrombolytic therapy SIR,-Thrombolytic therapy for the treatment of acute myocardial infarction has been associated with occasional reports of proteinuria and microscopic haematuria.1-5 These complications were noted in only a small percentage of individuals given streptokinase and formed part of a serum sickness or type-III hypersensitivity reaction. However, Argent and Adams6 reported microscopic haematuria or proteinuria for up to 24-48 h after that administration of streptokinase in 10 consecutive cases presenting with acute myocardial infarction. These patients had no features suggestive of an immunological cause for the complication. We have done a small prospective study to see if these findings were reproducible and if they were relevant to other thrombolytic agents. Urine from 66 consecutive patients admitted to a coronary care unit was tested for proteinuria and haematuria with dipsticks. 58 patients had positive tests, the abnormality lasting up to 72 h in some. The patients had normal erythrocyte sedimentation rates, there was no evidence of impairment of renal function and none had any features suggestive of a hypersensitivity reaction. 38 patients had been given anistreplase and 28 streptokinase. Renal histopathological findings were available in 1 patient given anistreplase 36 h before death. He had been proteinuria positive after thrombolysis. The glomeruli were microscopically normal. Immunohistochemical testing for IgA, IgD, IgG, IgM, C3, and fibrinogen was negative. This is suggestive, but not conclusive, that an immune cause is unlikely to be the underlying factor responsible for the microscopic haematuria and proteinuria. The mechanism remains unclear. These abnormalities may be secondary to a direct effect of thrombolytic agents on the glomeruli, resulting in increased permeability-or they may simply reflect the hypocoaguable state prevalent after use of thrombolytic agents. Royal Sussex County Hospital, Brighton, Sussex BN2 5BE, UK
R. S. MORE F. PEACOCK
RA, Joswig BC, Cheung AK, et al. Acute renal failure following repeated streptokinase therapy for pulmonary embolism. West J Med 1983; 138: 878. 2. Alexopoulos D, Raine AEG, Cobbe SM. Serum sickness complicating intravenous streptokinase therapy in acute myocardial infarction. Eur Heart J 1984; 5: 1010. 3. Murray N. Lyons J, Chappell M. Crescentic glomerulonephntis: a possible complication of streptokinase treatment for myocardial infarction. Br Heart J 1986, 1. Pick
56: 483.
Payne ST, Hosker HSR, Allen MB, et al. Transient impairment of renal function after streptokinase therapy. Lancet 1989; ii: 1398. 5. Callen MFC, Davies KAA, Merrin PK, et al. Proteinuna and thrombolytic agents. 4.
Lancet 1990; 335: 106. 6.
Argent N, Adams PC Proteinuria and thrombolytic agents
Lancet 1990; 335: 106.
Reduction of hypertension in hypovolaemia SIR,-Hypertension in association with hypovolaemia has been documented in several conditions.1,2 Hypertension during a nephrotic relapse can indicate serious underlying renal disease, but it can also be corrected by merely expanding the intravascular volume with plasma. We report two such patients for whom blood pressure and plasma renin activity data were available sequentially. Both patients had steroid-sensitive nephrotic syndrome and
acutely hypertensive during a relapse. Both were on prednisolone at full dosage and had clinical signs of hypovolaemia. Systolic blood pressure before plasma administration was 150 mm Hg in both. In the first patient, age 5 years, blood pressure fell progressively to normal over the next 12 h, associated with a fall in haemoglobin from 17 g/dl to 14 g/dl. In the second patient, age 10 years, blood pressure became normal over several days, and more colloid was given. Packed cell volume fell from 0-43 to 0 35. Serial plasma renin activities measured during these periods were 1075, 285, 307, 0 and 1403, 855, 570 ng AI/1 per h for each patient, respectively (normal range 130-830). We believe that the inappropriately high blood pressure associated with clinical signs of hypovolaemia seen in nephrotic relapse could, at least in part, result from oversecretion of renin in response to an inadequate circulatory volume, causing intense vasoconstriction and hence hypertension. This may be potentially more common in children because of their increased activity of the renin-angiotensin systemwhich may imply a greater reliance on this system for blood pressure homoeostasis. Plasma expansion, rather than antihypertensives, should be the priority in these circumstances and, indeed, hypotensive therapy is contraindicated. Our data also indicate that the absence of hypotension does not necessarily imply the presence of an inadequate circulatory volume. In addition, in view of the controversy about the role of plasma volume in nephrotic syndrome in adults,4 these data are further evidence that hypovolaemia may be a major complication of acute nephrotic relapse. became
Department of Paediatric Nephrology, Hospitals for Sick Children and Institute of Child Health, London WC1 N 1EH, UK
P. N. HOUTMAN V. SHAH T. M. BARRATT M. J. DILLON
1. Strickland
AL, Kotchen TA. A study of the renin-aldosterone system in congenital adrenal hyperplasia. J Pediatr 1972; 81: 962-69. 2. Cohn JN. Paroxysmal hypertension and hypovolemia. N Engl J Med 1966; 275: 643-46. 3. Dillon MJ, Ryness JM, Plasma renin activity and aldosterone concentration in children. Br Med J 1975; iv: 316-19. 4. Geers AB, Koomans HA, Boer P, et al. Plasma and blood volumes in patients with the nephrotic syndrome. Nephron 1984; 38: 170-73.
Doxorubicin/methotrexate/fluorouracil in advanced
pancreatic cancer
SIR,-Dr Pyrhonen and Dr Valtonen (July 14, p 127) report two patients with advanced pancreatic adenocarcinoma who had good primary response when treated with doxorubicin/methotrexate/ fluorouracil combination chemotherapy, a regimen also recently used for treatment of gastric cancer.1 We have started a phase II study of this regimen in untreated patients with advanced pancreatic cancer. We have treated 6 patients with doxor’ubicin (12 mg/m2, bolus injection), methotrexate (150 mg/m2, 30 min infusion), and 5-fluorouracil (500 mg/m2, 30 min infusion starting 1 h after administration of methotrexate). Citrovorum factor rescue is started 24 h after methotrexate, and each cycle is given once a week for 3 weeks then resumed after a 2-week interval. None of our patients had an objective response to therapy. The average survival time was 13-5 weeks (range 4-15), a disappointing figure considering that untreated patients are reported to have a 14-week average survival Moreover, patients had severe therapy-related side-effects, such as grade II myelosuppression (in 4 patients), grade II diarrhoea (2), and severe mucositis (3). 3 additional patients with advanced pancreatic cancer refused chemotherapy and were treated symptomatically-eg, albumin, anabolising steroids, analgesics,
absorbing surface, and any of the allergic rubber leachables (MET, raw latex, sulphites), appearing at random in rubber retention enema tips as a result of batch processing may cause allergic reactions when used for barium enema examinations. Lancet readers world wide should ask government regulatory bodies and manufacturers when natural rubber manufactured with MET was last used in unit-dose syringes and what are the expiry dates of the
drugs involved? 600 Colborne Street, London, Ontario N6B 2V2, Canada
GAVIN HAMILTON
Spaner D, Dolovich J, Tarlo S, Sussman G. Hypersensitivity to natural latex. J Allergy Clin Immunol 1989; 83: 1135-37. 2. Fisher AA. Management of dermatitis due to surgical gloves. J Dermatol Surg Oncol 1.
1985; 11: 628-31. 3. Hamilton G. Contamination of contrast agent by MBT in rubber seals. CMAJ 1987; 136: 1020-21. 4. Meek JH, Pettit BR. Avoidable accumulation of potentially toxic levels of benzothiazoles in babies receiving intravenous therapy. Lancet 1985; ii: 1090-92. 5. Graham DT, Mark, GE, Pomeroy AR. Chemical leaching from Terumo syringe seals. Aust NZ J Med 1982; 12: 305-06. 6. Bettmann MA. Ionic versus nonionic contrast agents for intravenous uses: are all the answers in? Radiology 1990; 175: 616-18. 7. Katayama H, Yamaguchi K, Kosuka T, Takashima T, Seez P, Matsuura T. Reactions to ionic and nonionic contrast media. Radiology 1990; 175: 621-28. 8. Napke E, Stevens DGH. Excipients and additives: hidden hazards in drug products and in product substitution. CMAJ 1984; 131: 1449-52. 9. Blais P. The impact of medical devices on quality of pharmaceuticals. In: Warbick-Cerone A, Johnston LG, eds. Quality assurance of pharmaceuticals manufactured in the hospitals. New York: Pergamon, 1985: 83-93.
Haematuria and proteinuria after
thrombolytic therapy SIR,-Thrombolytic therapy for the treatment of acute myocardial infarction has been associated with occasional reports of proteinuria and microscopic haematuria.1-5 These complications were noted in only a small percentage of individuals given streptokinase and formed part of a serum sickness or type-III hypersensitivity reaction. However, Argent and Adams6 reported microscopic haematuria or proteinuria for up to 24-48 h after that administration of streptokinase in 10 consecutive cases presenting with acute myocardial infarction. These patients had no features suggestive of an immunological cause for the complication. We have done a small prospective study to see if these findings were reproducible and if they were relevant to other thrombolytic agents. Urine from 66 consecutive patients admitted to a coronary care unit was tested for proteinuria and haematuria with dipsticks. 58 patients had positive tests, the abnormality lasting up to 72 h in some. The patients had normal erythrocyte sedimentation rates, there was no evidence of impairment of renal function and none had any features suggestive of a hypersensitivity reaction. 38 patients had been given anistreplase and 28 streptokinase. Renal histopathological findings were available in 1 patient given anistreplase 36 h before death. He had been proteinuria positive after thrombolysis. The glomeruli were microscopically normal. Immunohistochemical testing for IgA, IgD, IgG, IgM, C3, and fibrinogen was negative. This is suggestive, but not conclusive, that an immune cause is unlikely to be the underlying factor responsible for the microscopic haematuria and proteinuria. The mechanism remains unclear. These abnormalities may be secondary to a direct effect of thrombolytic agents on the glomeruli, resulting in increased permeability-or they may simply reflect the hypocoaguable state prevalent after use of thrombolytic agents. Royal Sussex County Hospital, Brighton, Sussex BN2 5BE, UK
R. S. MORE F. PEACOCK
RA, Joswig BC, Cheung AK, et al. Acute renal failure following repeated streptokinase therapy for pulmonary embolism. West J Med 1983; 138: 878. 2. Alexopoulos D, Raine AEG, Cobbe SM. Serum sickness complicating intravenous streptokinase therapy in acute myocardial infarction. Eur Heart J 1984; 5: 1010. 3. Murray N. Lyons J, Chappell M. Crescentic glomerulonephntis: a possible complication of streptokinase treatment for myocardial infarction. Br Heart J 1986, 1. Pick
56: 483.
Payne ST, Hosker HSR, Allen MB, et al. Transient impairment of renal function after streptokinase therapy. Lancet 1989; ii: 1398. 5. Callen MFC, Davies KAA, Merrin PK, et al. Proteinuna and thrombolytic agents. 4.
Lancet 1990; 335: 106. 6.
Argent N, Adams PC Proteinuria and thrombolytic agents
Lancet 1990; 335: 106.
Reduction of hypertension in hypovolaemia SIR,-Hypertension in association with hypovolaemia has been documented in several conditions.1,2 Hypertension during a nephrotic relapse can indicate serious underlying renal disease, but it can also be corrected by merely expanding the intravascular volume with plasma. We report two such patients for whom blood pressure and plasma renin activity data were available sequentially. Both patients had steroid-sensitive nephrotic syndrome and
acutely hypertensive during a relapse. Both were on prednisolone at full dosage and had clinical signs of hypovolaemia. Systolic blood pressure before plasma administration was 150 mm Hg in both. In the first patient, age 5 years, blood pressure fell progressively to normal over the next 12 h, associated with a fall in haemoglobin from 17 g/dl to 14 g/dl. In the second patient, age 10 years, blood pressure became normal over several days, and more colloid was given. Packed cell volume fell from 0-43 to 0 35. Serial plasma renin activities measured during these periods were 1075, 285, 307, 0 and 1403, 855, 570 ng AI/1 per h for each patient, respectively (normal range 130-830). We believe that the inappropriately high blood pressure associated with clinical signs of hypovolaemia seen in nephrotic relapse could, at least in part, result from oversecretion of renin in response to an inadequate circulatory volume, causing intense vasoconstriction and hence hypertension. This may be potentially more common in children because of their increased activity of the renin-angiotensin systemwhich may imply a greater reliance on this system for blood pressure homoeostasis. Plasma expansion, rather than antihypertensives, should be the priority in these circumstances and, indeed, hypotensive therapy is contraindicated. Our data also indicate that the absence of hypotension does not necessarily imply the presence of an inadequate circulatory volume. In addition, in view of the controversy about the role of plasma volume in nephrotic syndrome in adults,4 these data are further evidence that hypovolaemia may be a major complication of acute nephrotic relapse. became
Department of Paediatric Nephrology, Hospitals for Sick Children and Institute of Child Health, London WC1 N 1EH, UK
P. N. HOUTMAN V. SHAH T. M. BARRATT M. J. DILLON
1. Strickland
AL, Kotchen TA. A study of the renin-aldosterone system in congenital adrenal hyperplasia. J Pediatr 1972; 81: 962-69. 2. Cohn JN. Paroxysmal hypertension and hypovolemia. N Engl J Med 1966; 275: 643-46. 3. Dillon MJ, Ryness JM, Plasma renin activity and aldosterone concentration in children. Br Med J 1975; iv: 316-19. 4. Geers AB, Koomans HA, Boer P, et al. Plasma and blood volumes in patients with the nephrotic syndrome. Nephron 1984; 38: 170-73.
Doxorubicin/methotrexate/fluorouracil in advanced
pancreatic cancer
SIR,-Dr Pyrhonen and Dr Valtonen (July 14, p 127) report two patients with advanced pancreatic adenocarcinoma who had good primary response when treated with doxorubicin/methotrexate/ fluorouracil combination chemotherapy, a regimen also recently used for treatment of gastric cancer.1 We have started a phase II study of this regimen in untreated patients with advanced pancreatic cancer. We have treated 6 patients with doxor’ubicin (12 mg/m2, bolus injection), methotrexate (150 mg/m2, 30 min infusion), and 5-fluorouracil (500 mg/m2, 30 min infusion starting 1 h after administration of methotrexate). Citrovorum factor rescue is started 24 h after methotrexate, and each cycle is given once a week for 3 weeks then resumed after a 2-week interval. None of our patients had an objective response to therapy. The average survival time was 13-5 weeks (range 4-15), a disappointing figure considering that untreated patients are reported to have a 14-week average survival Moreover, patients had severe therapy-related side-effects, such as grade II myelosuppression (in 4 patients), grade II diarrhoea (2), and severe mucositis (3). 3 additional patients with advanced pancreatic cancer refused chemotherapy and were treated symptomatically-eg, albumin, anabolising steroids, analgesics,