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Thalidomide for systemic lupus erythematosus
1057
Analyses of river water have shown that it contained V cholerae only after arrival in Piura. This could explain the absence of symptomless carriers in group A. Munsen, in 1915, recognised the importance of symptomless carriage in maintaining cholera infection.6 Our findings support Levine’s prediction3that with the return of warm weather in January, 1992, cholera transmission in Peru could increase once again. Institute of Clinical Medicine, Faculty of Medicine and Surgery, Universitá Cattolica del S. Cuore,
Rome, Italy,
Ospedale S Biagio, Domodossola, Italy; Medical Centre,
University of Piura, Piura. Peru, and Department of Health, Piura
LUIGI PUGLIELLI CORRADO CATTRINI JOSÉ JULIAN GARCÉS RESA MARIA VELÁSQUES LUIS MIGUEL LEON GARCIA
1W7
Transaminase levels
(ALAT) (L1)
and abdominal
perimeter (.).
1. Centers for Disease Control.
Cholera-Peru, 1991. MMWR 1991, 40: 108-10. 2. World Health Organisation. Cholera: the epidemic in Peru. Wkly Epidemiol Rec 1991; 10: 65-70. 3 Levme MM. South America: the return of cholera. Lancet 1991; 338: 45-46. 4 MacKenzie DJM. Cholera and its control. In: Proceedings of Cholera Research Symposium (Honolulu, 1965). Washington, DC. US Government Printing Office, 1965: 341-46. 5. MacKenzie DJM. Cholera: whither prevention? Med Clin N Am 1967; 51: 625-35. 6. Munsen EL. Cholera carriers in relation to cholera control. Philippine J Sci 1915, 10: 1-9.
when the VOD was no longer thought to be life-threatening and the patient was doing well a severe interstitial pneumonitis developed. Bronchoalveolar lavage indicated a gram-negative infection. Despite massive antibiotic therapy, the patient died 1 week later from pneumonitis, septic shock, and renal failure. Necropsy confirmed VOD. In view of the very poor prognosis of liver VOD, r-tPA should be further tested.
Alteplase for hepatic veno-occlusive disease complicating bone-marrow transplantation S!R,—Veno-ocdusive disease of the liver (VOD) is a serious major complication of bone-marrow transplantation, being reported in 5-21 % of patients. 1-3 Attempts at prevention, including our own with heparin have failed although prostaglandin Ez (PGEz) looks promising.s Once VOD is diagnosed there is no proven specific therapy, and the case-fatality rate may reach 50%. Baglin et al6 reported success with recombinant tissue plasminogen activator (r-tPA) in one case. We have had a similar experience. A 45-year-old woman was diagnosed as having a Philadelphiapositive chronic myelocytic leukaemia (CML) in December, 1988. She had been on hydroxyurea and interferon until transplantation for which she was prepared with busulphan and cyclophosphamide. On Dec 27, 1991, she was grafted with marrow from her HLA-identical, MLC (mixed lymphocyte culture) negative brother. Graft-versus-host disease (GVHD) prophylaxis was given with cyclosporin and a short course of methotrexate. In an attempt to prevent VOD she was given PGEz (0-5 mg daily by continuous infusion). On day 4, the platelet count dropped abruptly and the patient became refractory to platelet transfusions.’ On day 7, increases in transaminases and bilirubin were noted and on day 10 she had a severe gastrointestinal haemorrhage with a grade IV mucositis related to the toxicity of the busulphan/ cyclophosphamide. On day 11 jaundice, oedema, hepatomegaly, and pronounced ascites developed. Echotomography ruled out obstruction of the hepatic veins. There was no sign of GVHD. The concentration of cyclosporin in blood was in the expected range (206 ng/ml). Serological test and virus cultures were negative for hepatitis (A, B, C) and cytomegalovirus infection. Liver VOD was diagnosed. The patient was given dopamine and diuretics, with no improvement. By day 15, the ascites and liver enlargement had considerably increased resulting in a visible deformation of the right upper quadrant. Alteplase (Actilyse) was started on day 15 at a dose of 50 mg over 3 h intravenously for 4 consecutive days. Within 48 h, the liver was much reduced and the ascites had disappeared. The abdominal perimeter returned to normal by day 20 (figure) and transaminases were much lower although serum bilirubin was still increasing (up to 400 mol/1). Special attention was devoted to the risk of bleeding in this patient, who had had a severe gastrointestinal hemorrhage 5 days earlier. No bleeding, however, occurred during r-tPA therapy. Daily blood coagulation tests indicated a decrease in fibrinogen concentration from 4-2 g/1 on day 14 to 2 g/1 on day 19. There was no other modification; fibrin-degradation products (D-dimers), present at 4 mg/1 on day 14 were unchanged by day 19. The graft was successful (polymorphs above 05 x 109/1 on day 16); the need for platelet transfusions decreased. Unfortunately, just
J. PH. LAPORTE S. LESAGE P. TILLEUL A. NAJMAN N. C. GORIN
Departments of Haematology, and Pharmacy, Hôpital Saint-Antoine, 75571 Paris, France
1. McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED. Venoocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence and predisposing factors. Hepatology 1984; 4: 116-22. 2. Bearman SI, Appelbaum FR, Buckner CD, et al. Regimen-related toxicity in patients undergoing bone marrow transplantation J Clin Oncol 1988; 6: 1562-68 3. Shulman HM, Gown AM, Nugent DJ. Hepatic veno-occlusive disease after bone marrow transplantation: immunohistochemical identification of the material within occluded venules. Am J Pathol 1987; 127: 549-58. 4. Marsa-Vila L, Gorin NC, Laporte JPh, et al. Prophylactic heparin does not prevent liver veno-occlusive disease following autologous bone marrow transplantation. Eur J Haematol 1991; 47: 346-54. 5. Gluckman E, Jolivet I, Scrobohaci ML, et al Use of prostaglandin E1 for prevention of liver veno-occlusive disease in leukaemic patients treated by allogeneic bone marrow transplantation. Br J Haematol 1990; 74: 277-81. 6. Baglin TP, Harper P, Marcus RE Veno-occlusive disease of the liver complicating ABMT successfully treated with recombinant tissue plasminogen activator (r-TPA) Bone Marrow Transplant 1990; 5: 439-41. 7. Rio B, Andreu G, Nicod A, et al Thrombocytopenia in veno-occlusive disease after bone marrow transplantation or chemotherapy. Blood 1986; 67: 1773-76.
Thalidomide for
systemic lupus
erythematosus S!R,—Those obstetricians who saw the consequences of the use of thalidomide in the late 1950s will view the report by Dr Bessis and colleagues (Feb 29, p 549) of the use of this agent in women of reproductive age with grave alarm. The problem of the 1950s still presents to us-women with thalidomide phocomelia are having their own babies. When will physicians appreciate that there is no such thing as a "strict contraceptive measure", short of total abstinence? If thalidomide is used, there will be the usual 1-5% of contraceptive failures and women who are unable to contemplate legal abortion will produce grossly abnormal babies. With the present armamentarium of drugs effective in systemic lupus erythematosus, it is surprising that rheumatologists should have found it acceptable to use this toxic chemical. It has clearly lost none of its toxicity, since one of the three patients Bessis et al report whose remissions happened to coincide with the use of thalidomide had the peripheral neuropathy that caused such distress to so many patients when this drug was used before. Is it not time that all remaining supplies of thalidomide tablets were consigned to the flames? Department of Obstetrics and Gynaecology, Hammersmith Hospital, London W12 OHS, UK
D. F. HAWKINS
Analyses of river water have shown that it contained V cholerae only after arrival in Piura. This could explain the absence of symptomless carriers in group A. Munsen, in 1915, recognised the importance of symptomless carriage in maintaining cholera infection.6 Our findings support Levine’s prediction3that with the return of warm weather in January, 1992, cholera transmission in Peru could increase once again. Institute of Clinical Medicine, Faculty of Medicine and Surgery, Universitá Cattolica del S. Cuore,
Rome, Italy,
Ospedale S Biagio, Domodossola, Italy; Medical Centre,
University of Piura, Piura. Peru, and Department of Health, Piura
LUIGI PUGLIELLI CORRADO CATTRINI JOSÉ JULIAN GARCÉS RESA MARIA VELÁSQUES LUIS MIGUEL LEON GARCIA
1W7
Transaminase levels
(ALAT) (L1)
and abdominal
perimeter (.).
1. Centers for Disease Control.
Cholera-Peru, 1991. MMWR 1991, 40: 108-10. 2. World Health Organisation. Cholera: the epidemic in Peru. Wkly Epidemiol Rec 1991; 10: 65-70. 3 Levme MM. South America: the return of cholera. Lancet 1991; 338: 45-46. 4 MacKenzie DJM. Cholera and its control. In: Proceedings of Cholera Research Symposium (Honolulu, 1965). Washington, DC. US Government Printing Office, 1965: 341-46. 5. MacKenzie DJM. Cholera: whither prevention? Med Clin N Am 1967; 51: 625-35. 6. Munsen EL. Cholera carriers in relation to cholera control. Philippine J Sci 1915, 10: 1-9.
when the VOD was no longer thought to be life-threatening and the patient was doing well a severe interstitial pneumonitis developed. Bronchoalveolar lavage indicated a gram-negative infection. Despite massive antibiotic therapy, the patient died 1 week later from pneumonitis, septic shock, and renal failure. Necropsy confirmed VOD. In view of the very poor prognosis of liver VOD, r-tPA should be further tested.
Alteplase for hepatic veno-occlusive disease complicating bone-marrow transplantation S!R,—Veno-ocdusive disease of the liver (VOD) is a serious major complication of bone-marrow transplantation, being reported in 5-21 % of patients. 1-3 Attempts at prevention, including our own with heparin have failed although prostaglandin Ez (PGEz) looks promising.s Once VOD is diagnosed there is no proven specific therapy, and the case-fatality rate may reach 50%. Baglin et al6 reported success with recombinant tissue plasminogen activator (r-tPA) in one case. We have had a similar experience. A 45-year-old woman was diagnosed as having a Philadelphiapositive chronic myelocytic leukaemia (CML) in December, 1988. She had been on hydroxyurea and interferon until transplantation for which she was prepared with busulphan and cyclophosphamide. On Dec 27, 1991, she was grafted with marrow from her HLA-identical, MLC (mixed lymphocyte culture) negative brother. Graft-versus-host disease (GVHD) prophylaxis was given with cyclosporin and a short course of methotrexate. In an attempt to prevent VOD she was given PGEz (0-5 mg daily by continuous infusion). On day 4, the platelet count dropped abruptly and the patient became refractory to platelet transfusions.’ On day 7, increases in transaminases and bilirubin were noted and on day 10 she had a severe gastrointestinal haemorrhage with a grade IV mucositis related to the toxicity of the busulphan/ cyclophosphamide. On day 11 jaundice, oedema, hepatomegaly, and pronounced ascites developed. Echotomography ruled out obstruction of the hepatic veins. There was no sign of GVHD. The concentration of cyclosporin in blood was in the expected range (206 ng/ml). Serological test and virus cultures were negative for hepatitis (A, B, C) and cytomegalovirus infection. Liver VOD was diagnosed. The patient was given dopamine and diuretics, with no improvement. By day 15, the ascites and liver enlargement had considerably increased resulting in a visible deformation of the right upper quadrant. Alteplase (Actilyse) was started on day 15 at a dose of 50 mg over 3 h intravenously for 4 consecutive days. Within 48 h, the liver was much reduced and the ascites had disappeared. The abdominal perimeter returned to normal by day 20 (figure) and transaminases were much lower although serum bilirubin was still increasing (up to 400 mol/1). Special attention was devoted to the risk of bleeding in this patient, who had had a severe gastrointestinal hemorrhage 5 days earlier. No bleeding, however, occurred during r-tPA therapy. Daily blood coagulation tests indicated a decrease in fibrinogen concentration from 4-2 g/1 on day 14 to 2 g/1 on day 19. There was no other modification; fibrin-degradation products (D-dimers), present at 4 mg/1 on day 14 were unchanged by day 19. The graft was successful (polymorphs above 05 x 109/1 on day 16); the need for platelet transfusions decreased. Unfortunately, just
J. PH. LAPORTE S. LESAGE P. TILLEUL A. NAJMAN N. C. GORIN
Departments of Haematology, and Pharmacy, Hôpital Saint-Antoine, 75571 Paris, France
1. McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED. Venoocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence and predisposing factors. Hepatology 1984; 4: 116-22. 2. Bearman SI, Appelbaum FR, Buckner CD, et al. Regimen-related toxicity in patients undergoing bone marrow transplantation J Clin Oncol 1988; 6: 1562-68 3. Shulman HM, Gown AM, Nugent DJ. Hepatic veno-occlusive disease after bone marrow transplantation: immunohistochemical identification of the material within occluded venules. Am J Pathol 1987; 127: 549-58. 4. Marsa-Vila L, Gorin NC, Laporte JPh, et al. Prophylactic heparin does not prevent liver veno-occlusive disease following autologous bone marrow transplantation. Eur J Haematol 1991; 47: 346-54. 5. Gluckman E, Jolivet I, Scrobohaci ML, et al Use of prostaglandin E1 for prevention of liver veno-occlusive disease in leukaemic patients treated by allogeneic bone marrow transplantation. Br J Haematol 1990; 74: 277-81. 6. Baglin TP, Harper P, Marcus RE Veno-occlusive disease of the liver complicating ABMT successfully treated with recombinant tissue plasminogen activator (r-TPA) Bone Marrow Transplant 1990; 5: 439-41. 7. Rio B, Andreu G, Nicod A, et al Thrombocytopenia in veno-occlusive disease after bone marrow transplantation or chemotherapy. Blood 1986; 67: 1773-76.
Thalidomide for
systemic lupus
erythematosus S!R,—Those obstetricians who saw the consequences of the use of thalidomide in the late 1950s will view the report by Dr Bessis and colleagues (Feb 29, p 549) of the use of this agent in women of reproductive age with grave alarm. The problem of the 1950s still presents to us-women with thalidomide phocomelia are having their own babies. When will physicians appreciate that there is no such thing as a "strict contraceptive measure", short of total abstinence? If thalidomide is used, there will be the usual 1-5% of contraceptive failures and women who are unable to contemplate legal abortion will produce grossly abnormal babies. With the present armamentarium of drugs effective in systemic lupus erythematosus, it is surprising that rheumatologists should have found it acceptable to use this toxic chemical. It has clearly lost none of its toxicity, since one of the three patients Bessis et al report whose remissions happened to coincide with the use of thalidomide had the peripheral neuropathy that caused such distress to so many patients when this drug was used before. Is it not time that all remaining supplies of thalidomide tablets were consigned to the flames? Department of Obstetrics and Gynaecology, Hammersmith Hospital, London W12 OHS, UK
D. F. HAWKINS