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Prolongation of fibrinolytic activity of tissue plasminogen activator by nitrovasodilators
669
Fig 2-Representative G-banded karyotype of tumour cells.
combination with heparin seemed to explain the bleeding. However, in contrast to the other trials, all patients in the angina pectoris group were simultaneously treated with a standard drug regimen, consisting mainly of nitrovasodilators. We speculated that the bleeding observed resulted from the prolongation of the fibrinolytic activity of t-PA by nitrovasodilators. To test this hypothesis we have done some experiments in New Zealand white rabbits anaesthetised with sodium pentobarbitone (20 mg/kg intravenously). Fibrinolytic activity was estimated by measuring t-PA activity (’Spectrolyse’ kit; Biopool, Sweden) in plasma before and 1, 5, 15, 30, and 60 min after the intravenous administration of single-chain t-PA (30 )Jg/kg; Biopool) and/or sodium nitroprusside (30 pg/kg; Sigma). Injection of t-PA increased t-PA activity in the sample drawn after 1 min, but activity had returned to baseline within 5 min (figure). Sodium nitroprusside alone had little effect on t-PA activity (from 0 48 but co[SEM 0-05] to 0-73 [0’09] IU/ml, n=4; p<0-01) administration of nitroprusside with t-PA resulted in significant prolongation of t-PA activity (figure).
Karyotype is 50,XX,+X,-1,+3,+7,-19,+der(1;?)(p36:?),+mar1, +mar2 Arrows indicate abnormalities.
cytogenetic abnormalities detected in this case point to neoplasia while the molecular genetic studies indicate clonal expansion of the B-cell population. These findings support the view of Isaacson et a15,6 that extranodal lymphoid hyperplasia (previously "pseudolymphoma") is not a reactive process but a distinct clinical entity-namely, malignant lymphoma of mucosa-associated lymphoid tissue. Department of Haematology, Atomic Disease Institute, Nagasaki University School of Medicine,
Nagasaki 852, Japan
TAKAHIRO ITOYAMA NAOKI SADAMORI MICHITO ICHIMARU
Second
Department of Internal Medicine, Nagasaki University School of Medicine
REIKO SENJU MASAKI HIROTA
First Department of Pathology, Fukuoka University School of Medicine
TAKAHISA YOSHIDA MASAHIRO KIKUCHI
Mitsubishi Yuka Bio-Clinical Laboratories, Tokyo
SHUNJI YAMAMORI SHOICHI SHIMIZU
SL. Pulmonary malignant lymphomas and pseudolymphomas: classification, therapy, and prognosis. Cancer 1963; 16: 928-55. 2 Fishleder A, Tubbs R, Hesse B, Levine H. Uniform detection of immunoglobulin1987; 316: gene rearrangement in benign lymphoepithelial lesions. N Engl Med J
1 Saltzstein
1118-21. 3. Knowles DM, Athan E, Ubriaco A, et al. Extranodal noncutaneous lymphoid hyperplasias represent a continuous spectrum of B-cell neoplasia: demonstration by molecular genetic analysis. Blood 1989; 73: 1635-45. 4. Spencer J, Diss TC, Isaacson PG. Primary B cell gastnc lymphoma: a genotipic analysis. Am J Pathol 1989; 135: 557-64. 5. Isaacson P, Wright DH. Extranodal malignant lymphoma arising from mucosaassociated lymphoid tissue. Cancer 1984; 53: 2515-24. 6. Isaacson PG, Spencer J. Malignant lymphoma of mucosa-associated lymphoid tissue. Histopathology 1987; 11: 445-62.
in plasma t-PA activity after intravenous administration of sodium nitroprusside (A; n = 3), t-PA (.; n=3), or both (0; n=3) to anaesthetised rabbits.
Change
Results analysed by two-way analysis of variance followed by a least significance procedure (***p < 001, **p < 01).
The bleeding tendency and reduced t-PA requirement in patients with angina pectoris treated with alteplase4 may result from the prolongation of t-PA activity due to combined treatment with nitrovasodilators. The administration of nitrovasodilators in combination with alteplase may have important therapeutic consequences, perhaps allowing a reduction in the total dose of
alteplase.
Prolongation of fibrinolytic activity of tissue plasminogen activator by nitrovasodilators SiR,—Alteplase (recombinant tissue plasminogen activator, rt-PA) recanalises occluded coronary arteries in 50-89% of patients with acute myocardial infarction.1 rt-PA may also be useful in other thromboembolic conditions, such as pulmonary embolism, stroke, arterial occlusion, deep-vein thrombosis, and unstable angina pectoris.l In clinical practice concerns about rt-PA have centred on the risk of systemic fibrinolytic activation and bleeding complications. Although this risk can be reduced by using doses adjusted to body weight (1 mg/kg over 90 min),2 major bleeding tendencies still occurred in 29% of patients. The risk seems to be greater in patients with unstable angina than in other thromboembolic disorders: Gold et al4 found that rt-PA was associated with bleeding in 8 of 12 patients whereas no bleeding was observed in the placebo group. Neither high doses of rt-PA nor its
This institute is
supported by a grant from Glaxo Group Research Ltd.
William Harvey Research Institute, St Bartholomew’s Hospital Medical London EC1M 6BQ, UK
College,
R. KORBUT P. S. LIDBURY J. R. VANE
1. Collen
D, Lijnen HR, Todd PA, Goa KL. Tissue-type plasminogen activator: a review of its pharmacology and therapeutic use as a thrombolytic agent. Drugs 1989; 38: 346-88.
Topol EJ, George BS, Kereiakes DJ, et al. Comparison of two dose regimens of intravenous tissue plasminogen activator for acute myocardial infarction. Am J Cardiol 1988; 61: 723-28. 3. Van de Werf F, Arnold AER, the European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator. Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute myocardial infarction. Br Med J 1988; 297: 1374-79. 4. Gold HK, Johns JA, Leinbach RC, et al. A randomized, blinded, placebo-controlled trial of recombinant human tissue-type plasminogen activator in unstable angina pectons. Circulation 1987; 75: 1192-99. 2.
Fig 2-Representative G-banded karyotype of tumour cells.
combination with heparin seemed to explain the bleeding. However, in contrast to the other trials, all patients in the angina pectoris group were simultaneously treated with a standard drug regimen, consisting mainly of nitrovasodilators. We speculated that the bleeding observed resulted from the prolongation of the fibrinolytic activity of t-PA by nitrovasodilators. To test this hypothesis we have done some experiments in New Zealand white rabbits anaesthetised with sodium pentobarbitone (20 mg/kg intravenously). Fibrinolytic activity was estimated by measuring t-PA activity (’Spectrolyse’ kit; Biopool, Sweden) in plasma before and 1, 5, 15, 30, and 60 min after the intravenous administration of single-chain t-PA (30 )Jg/kg; Biopool) and/or sodium nitroprusside (30 pg/kg; Sigma). Injection of t-PA increased t-PA activity in the sample drawn after 1 min, but activity had returned to baseline within 5 min (figure). Sodium nitroprusside alone had little effect on t-PA activity (from 0 48 but co[SEM 0-05] to 0-73 [0’09] IU/ml, n=4; p<0-01) administration of nitroprusside with t-PA resulted in significant prolongation of t-PA activity (figure).
Karyotype is 50,XX,+X,-1,+3,+7,-19,+der(1;?)(p36:?),+mar1, +mar2 Arrows indicate abnormalities.
cytogenetic abnormalities detected in this case point to neoplasia while the molecular genetic studies indicate clonal expansion of the B-cell population. These findings support the view of Isaacson et a15,6 that extranodal lymphoid hyperplasia (previously "pseudolymphoma") is not a reactive process but a distinct clinical entity-namely, malignant lymphoma of mucosa-associated lymphoid tissue. Department of Haematology, Atomic Disease Institute, Nagasaki University School of Medicine,
Nagasaki 852, Japan
TAKAHIRO ITOYAMA NAOKI SADAMORI MICHITO ICHIMARU
Second
Department of Internal Medicine, Nagasaki University School of Medicine
REIKO SENJU MASAKI HIROTA
First Department of Pathology, Fukuoka University School of Medicine
TAKAHISA YOSHIDA MASAHIRO KIKUCHI
Mitsubishi Yuka Bio-Clinical Laboratories, Tokyo
SHUNJI YAMAMORI SHOICHI SHIMIZU
SL. Pulmonary malignant lymphomas and pseudolymphomas: classification, therapy, and prognosis. Cancer 1963; 16: 928-55. 2 Fishleder A, Tubbs R, Hesse B, Levine H. Uniform detection of immunoglobulin1987; 316: gene rearrangement in benign lymphoepithelial lesions. N Engl Med J
1 Saltzstein
1118-21. 3. Knowles DM, Athan E, Ubriaco A, et al. Extranodal noncutaneous lymphoid hyperplasias represent a continuous spectrum of B-cell neoplasia: demonstration by molecular genetic analysis. Blood 1989; 73: 1635-45. 4. Spencer J, Diss TC, Isaacson PG. Primary B cell gastnc lymphoma: a genotipic analysis. Am J Pathol 1989; 135: 557-64. 5. Isaacson P, Wright DH. Extranodal malignant lymphoma arising from mucosaassociated lymphoid tissue. Cancer 1984; 53: 2515-24. 6. Isaacson PG, Spencer J. Malignant lymphoma of mucosa-associated lymphoid tissue. Histopathology 1987; 11: 445-62.
in plasma t-PA activity after intravenous administration of sodium nitroprusside (A; n = 3), t-PA (.; n=3), or both (0; n=3) to anaesthetised rabbits.
Change
Results analysed by two-way analysis of variance followed by a least significance procedure (***p < 001, **p < 01).
The bleeding tendency and reduced t-PA requirement in patients with angina pectoris treated with alteplase4 may result from the prolongation of t-PA activity due to combined treatment with nitrovasodilators. The administration of nitrovasodilators in combination with alteplase may have important therapeutic consequences, perhaps allowing a reduction in the total dose of
alteplase.
Prolongation of fibrinolytic activity of tissue plasminogen activator by nitrovasodilators SiR,—Alteplase (recombinant tissue plasminogen activator, rt-PA) recanalises occluded coronary arteries in 50-89% of patients with acute myocardial infarction.1 rt-PA may also be useful in other thromboembolic conditions, such as pulmonary embolism, stroke, arterial occlusion, deep-vein thrombosis, and unstable angina pectoris.l In clinical practice concerns about rt-PA have centred on the risk of systemic fibrinolytic activation and bleeding complications. Although this risk can be reduced by using doses adjusted to body weight (1 mg/kg over 90 min),2 major bleeding tendencies still occurred in 29% of patients. The risk seems to be greater in patients with unstable angina than in other thromboembolic disorders: Gold et al4 found that rt-PA was associated with bleeding in 8 of 12 patients whereas no bleeding was observed in the placebo group. Neither high doses of rt-PA nor its
This institute is
supported by a grant from Glaxo Group Research Ltd.
William Harvey Research Institute, St Bartholomew’s Hospital Medical London EC1M 6BQ, UK
College,
R. KORBUT P. S. LIDBURY J. R. VANE
1. Collen
D, Lijnen HR, Todd PA, Goa KL. Tissue-type plasminogen activator: a review of its pharmacology and therapeutic use as a thrombolytic agent. Drugs 1989; 38: 346-88.
Topol EJ, George BS, Kereiakes DJ, et al. Comparison of two dose regimens of intravenous tissue plasminogen activator for acute myocardial infarction. Am J Cardiol 1988; 61: 723-28. 3. Van de Werf F, Arnold AER, the European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator. Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute myocardial infarction. Br Med J 1988; 297: 1374-79. 4. Gold HK, Johns JA, Leinbach RC, et al. A randomized, blinded, placebo-controlled trial of recombinant human tissue-type plasminogen activator in unstable angina pectons. Circulation 1987; 75: 1192-99. 2.