- Email: [email protected]
CLUSTER OF UNCOMMON FETAL ABNORMALITIES
1360 VIOLENCE AGAINST DOCTORS IN EL SALVADOR AND GUATEMALA
SIR,-Since the signing of the Geneva Convention in 1964 doctors and nurses as well as sick and wounded have been regarded as neutrals during conflict. These principles are being brutally disregarded in El Salvador and Guatemala today. According to information obtained from Amnesty International and from other sources, military and paramilitary groups have, in recent years, assassinated, tortured, and threatened doctors, nurses, and medical students. Such armed groups have also entered hospitals and shot patients. The governments of the two countries have never punished, prosecuted, or even identified those responsible for the killings. Here are a few examples: On May 15, 1980, Dr M. A. Garcia and Dr C. E. Rodrigues were kidnapped by armed men from a hospital in Cojutepeque, El Salvador, when performing an operation. Both doctors were later found dead with clear evidence of torture. Dr C. A. Vargas Lopez was arrested by security forces when leaving his clinic in San Salvador on Dec. 16, 1981. He has not been heard of since. Dr Arnoldo Merida Zuniga was seen last when led from his clinic in Guatemala City by a group of masked, armed men, on Dec 29, 1981. Dr Filiberto Sanchez Castillo was kidnapped in Guatemala City in August, 1981. Some days later he was found dead with signs of torture and bullet wounds. I urge colleagues to write to El Salvador and Guatemala asking the governments to take vigorous action to stop violations of medical neutrality and to ensure that all health personnel can treat people in need of care without fear of reprisal. Department of Internal Medicine, Central Hospital, S-301 85 Halmstad, Sweden
LOUISE HELLQUIST
**1982 cases of abduction or arrest in El Salvador known to the Central America research department of Amnesty International include: Dr O. A. Espinoza Martinez (Feb. 5); Dr Manuel de Paz Villata (Jan. 28); Dr R. P. Vazquez Gil (Jan. 19); and Dr H. V. Moran (February). Dr J. J. A. Hidalgo Salguero, who was abducted in Guatemala City, last September, was later found dead in the El Quiche region.-ED, L. MILD CLINICAL COURSE OF PERTUSSIS IN SWEDISH INFANTS OF TODAY
SIR,—Discussing salbutamol treatment of infants with pertussis Dr Peltola and Dr Michelsson (Feb. 6, p. 310) referred to a Swedish paper from 19701 when stating that "pertussis is most lifethreatening in infants who are less than 6 months old". However, in Sweden today not even for infants of that age is pertussis a serious disease. Despite the fact that since the mid-1970s pertussis has again become endemic in Sweden2and now has reached incidence rates approaching those of the pre-vaccination era, no child has died of pertussis since 1970. The clinical course of pertussis in Sweden has become milder. In an investigation of infants less than 6 months old with bacteriologically verified pertussis published in 19793 only 24/59 infants were admitted to hospital, in most cases for social reasons, and only 1 infant was considered as critically ill. During 1977-79, 19 000 cases of pertussis (but no deaths) were notified by district medical officers in Sweden. Sweden has a population of about 8 million so this figure is about the same as the number of notified cases in England and Wales during the same period, where 102 000 cases (and 28 deaths) were reported in a population of about 50 million. In Goteborg, where I work, I have found that in the school health records of a random sample of 743 1.
2. 3.
Strangert K. Clinical course and prognosis of whooping cough in Swedish children during the first six months of life: a study of hospitalized patients 1958-1967. Scand J Infect Dis 1970; 2: 45-48 Trollfors B, Rabo E Whooping cough in adults Br Med J 1981; 283: 696-97. Trollfors B. Clinical course of whooping cough in children younger than six months. Acta Paediatr Scand 1979; 68: 323-28
children born in 1974-nearly all of whom had had three injections of a Swedish made triple vaccine-parents had stated that 39, 4% of the children had already had pertussis when they began at school at the age of last autumn. In a similar study from the prevaccination era 48 - 9% of 2000 children born in 1949 had contracted pertussis before the age of eight years. Mass vaccination with a pertussis vaccine giving 90% immunity5 began in most parts of Sweden during the 1950s. From the middle of the 1960s more than 90% of all infants were vaccinated and pertussis became rare. The return of pertussis during the 1970s seems to have been related to changes in the production of the vaccine at the beginning of the 1970s,6which made the vaccine ineffective.2 Due to the ineffective vaccine and the present mild clinical course of pertussis in Sweden the vaccination was stopped in 1979. In view of the rare but serious neurological complications of whole cell pertussis vaccinesit was not considered appropriate to reintroduce an effective vaccine of this type. We are now eagerly awaiting the development of acellular and, it is to be hoped, nontoxic, pertussis vaccines. According to data presented at a workshop on new pertussis vaccines held at the National Institutes of Health, Bethesda in February of this year such a vaccine is now under clinical evaluation in Japan. Outpatient Department of Paediatrics, Västra Frölunda Hospital, S-421 22 Västra Frölunda, Sweden JOHN TARANGER
seven years
CLUSTER OF UNCOMMON FETAL ABNORMALITIES
SIR.—Four cases of unusual fetal abnormalities were detected at routine second trimester ultrasound examinations over a period of 18 days, during December, 1981, and January, 1982. All four pregnancies were terminated, and necropsy revealed remarkably similar features in all four cases (table). Genetic consultation with Prof. C. O. Carter suggests a risk of approximately 1 such abnormality in 20 000 births, and their chronological and geographical occurrence led to a search for common associations. None have been found to date and no further such cases are known to have occurred locally. During the 18 day period in question 596 ultrasound examinations were done, giving an incidence ofin 189, if the case is discounted. Since not all pregnant women are subjected to ultrasound examinations, further cases of these abnormalities may come to light 4. Ström J. Social development and declining incidence of some common epidemic diseases in children: a study of the incidence in different age groups in Stockholm. Acta Paediatr Scand 1967, 56: 159-63 5. Laurell G, Mellbin T, Rabo E, Vahlquist B, Zetterquist P. Systematische Impfung mit kombiniertem Impstoff (Diphterie, Tetanus, Pertussis) im Säuglingsalter. Serologische und klinische Studien. Klin Wochenschr 1957; 35: 920-24 6. Askelöf P Statement of the effect of various methods for inactivating pertussis vaccines In: Manclark CR, Hill JC, eds. International symposium on pertussis: DHEW (NIH) 79-1830. Washington, DC: US Government Printing Office, 1979: 368-69. 7. Miller DL, Ross EM, Alderslade R, Bellman M, Rawson NSB. Pertussis immunisation and serious acute neurological illness in children. Br Med J 1981, 282: 1595-99.
POST MORTEM FINDINGS OF ABNORMAL FETUSES
*This fetus also had patent "cord" between bladder neck and rectum;
no
bifurcation of
aorta; and gut malrotation.
Hypopl.=hypoplastic; hydronephr.=hydronephrosis; imperf. =imperforate; perf =perforate.
cyst. dyspl. = cysuc
dysplasia;
1361
during the next few months. The last normal menstrual periods of the four patients concerned were between Aug. 24 and Sept. 22, 198 L In the absence of any further cases, these 4 should probably be regarded as fortuitous. If other cases occur, however, a diligent search for a causative factor will be needed. Would obstetricians and pathologists notify me if they find a case with the abnormalities as tabulated? Institute of Obstetrics and
Gynaecology, Queen Charlotte’s Maternity Hospital,
M. J. BENNETT
London W6 0XG
ENALAPRIL (MK-421) AND THE WHITE CELL COUNT AND HAEMATOCRIT
SIR,-In response to the recent report of reversible leukopenia associated with MK-421 (enalapril maleate),! we would like to report our experience with complete blood counts and lack of association of leukopenia during a study of MK-421. MK-421 is a new, non-sulphydryl angiotensin-converting enzyme inhibitor which theoretically should be devoid of the penicillamine-like reactions associated with captopril, including rash, fever, proteinuria, neutropenia, and agranulocytosis.2,3 In the present prospective study, thirty normal and hypertensive volunteers received one of three medications: hydrochlorthiazide (HCTZ, 50 mg/day), MK-421(10 mg/day), or HCTZ (50 mg/day) plus MK-421I (10 mg/day) over 4-60 weeks. Blood studies were done regularly for multiple analyses, including complete blood counts. Results of the white count and haematocrit are shown in the table. WHITE CELL COUNTS AND HAEMATOCRITS IN PATIENTS ON HYDROCHLOROTHIAZIDE
(HCTZ),
ENALAPRIL
(MK-421), OR BOTH
*p<0-05.
has been demonstrated to increase plasma levels in normal and anephric rats before and after stimulation by either hypoxia or anaemia.5,6 Since the effect of converting enzyme blockade on erythropoietin levels remains to be studied in man it is impossible to know whether converting-enzyme inhibitors such as MK-421 could impair the erythropoietic response to stimuli like anaemia or hypoxia. In the limited experience afforded by this study, leukopenia or immunologically related syndromes appear to be very unusual with MK-421. After phlebotomy, a small decline in the haematocrit was ,seen in the two groups receiving MK-421 but not in the HCTZ alone group. This change was small, however, and does not constitute proof of a cause-and-effect relationship. In summary, MK-421 appeared to have few, if any, adverse haematological effects; however, careful haematological monitoring will be required until further data are available.
angiotensin-l! infusion
erythropoietin
Section
of Endocrinology and Metabolism, University Hospital,
GEORGE T. GRIFFING MELBY
JAMES C.
Boston, Massachusetts 02118, U.S.A.
T-CELL LEUKAEMIA A FEW MONTHS APART IN TWO BROTHERS
SIR,-Since adult T-cell leukaemia (ATL) was reported by Uchiyama et al.,111 out of 102 patients with ATL have revealed a family history of malignant lymphoma or leukaemia.2Here, we report a family of six siblings, of whom two men developed ATL almost simultaneously. A 51-year-old man was admitted to another hospital in December 1979, because of a 1 month history of heavy head sensation and anorexia. He had moderate hepatomegaly with some systemic lymphadenopathy. Hb 11-55 g/dl, platelets 54 x 109/1, and white blood cells 7 - 3 x 109/1 with 2% erythroblasts. Hypercalcaemia mmol, which is frequently seen in ATL, was noted among the laboratory data. Biopsy of a lymph node in the neck revealed malignant lymphoma, mixed type, diffuse. It was also diagnosed as diffuse lymphoma, pleomorphic type, according to the new classification in Japan (Lymphoma Study Group Classification),3 which is a usual feature ofATL. Combination chemotherapy ofvincristine (1-00 mg weekly) and prednisolone (20 mg daily) resulted in a poor response by malignant cells. The patient died of bleeding in March, 1980. The 60-year-old brother of the above patient was admitted to our hospital in April, 1980, complaining of facial oedema and exanthema of the skin with an itchy sensation. He had moderate hepatosplenomegaly and some systemic lymphadenopathy. Hb 14-3g/dl, platelets 194 x 109/1, and WBC 215 x 109/1, 95% of the cells being typical ATL. Bone marrow aspirate contained 74-8% of cells of similar morphology. 90% of leucocytes formed sheep red-blood-cell rosettes, 93% possessed T-cell surface antigen of peripheral T-cell type, and none of the leukaemic cells had TdT or common ALL antigens. None of the leukaemic cells possessed B-cell markers (SmIg, CIg, Ia-like antigen, or EAC receptors). The leukaemic cells also possessed OKT3, OKT8, and Tac antigens on their cell surfaces. The HLA haplotype was HLA A3,26,B44,-,C3,-. A diagnosis of ATL was supported by lymph node biopsy which revealed malignant lymphoma, diffuse, pleomorphic type (Lymphoma Study Group Classification. Leukapheresis and combination chemotherapy resulted in rapid and sustained clinical improvement.4 After 13 months of complete remission, the patient -
Although the WCC tended to decrease with the onset of therapy, this was insignificant in all three groups. Only two subjects had WCC counts below 4000 cells/1: one patient in the MK-421 group had an asymptomatic decrease from 6000 to 3900 /J.11 during the first week of treatment, and a patient on HCTZ group had a decrease from 4100 to 3600 during the first week (the nadir was 3000 and the WCC subsequently rose to 6300 cells/1). The leukopenia in both of these patients is probably related to phlebotomy (1300 ml over 33 days), since they had an associated fall in haematocrit of 49% to 41 % and 38% to 33%, respectively. Furthermore, they had no symptoms or manifestations of leukopenia or immune-related disease. There was a small but significant decrease in haematocrit in the MK-421 and HCTZ + MK-421 groups, but not the HCTZ group. The lack of a significant haematocrit decline in the HCTZ group could be due to diuretic-induced volume contraction and haemoconcentration, but this may not be. an adequate explanation, since the HCTZ + MK-421 group had evidence of greater volume contraction, reflected in a larger weight loss (2 - 3 vs 1 -6 kg) and a greater sodium deficit (251 vs 87 mmol) at day 7 and persisting up to day 28. It is impossible, in the present study, to explain fully or appreciate the significance of the slight differences in haematocrits, but it cannot be excluded that MK-421 was a contributing factor. It has been reported that angiotensin-II is necessary for maximal erythropoietin elaboration in certain animal models.4Subpressor 1. Studen
2. 3. 4.
A, Vetter W. Reversible leukopenia associated with angiotensin-converting inhibitor, MK-421. Lancet 1982; i: 458 Vidt DG, Bravo EL, Fouad FM. Captopril. N EnglJ Med 1982; 306: 214-19. van Brummelen P, Willemze R, Ran WD, Thompson J. Captopril-associated agranulocytosis. Lancet 1980; i: 150. Anagnostou A, Baranowski R, Pillay VKG, Kurtzman N, Vercellotti G, Fried W. Effect of renin on extra renal erythropoietin production. J Lab Clin Med 1976; 88: 707-18.
5. Gould
AB, Goodman S, DeWolf R,
et
al. Interrelation of the
renin
system and
J Lab Clin Med 1980; 96: 523-33 6. Fried W, Barone-Varelas J, Barone T, Anagnostou A. Effect ofangiotensin infusion on extra renal erythropoitin production J Lab Clin Med 1982, 99: 520-25. I Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H Adult T-cell leukemia:
erythropoietin
in
rats.
clinical and hematologic features of 16 cases. Blood 1977; 50: 481-92. 2 The T- and B-cell Malignancy Study Group. Statistical analysis of immunologic, clinical and histopathologic data on lymphoid malignancies in Japan Japan J Clin
Oncol 1981; 11: 15-38. T, Tajima K, Nanba K,
et al Some problems on the histopathological diagnosis of non-Hodgkin’s malignant lymphoma. a proposal of a new type. Acta Pathol Jap
3. Suchi
1979, 29: 755-76. N, Tokumo K, Koganemaru S, Oguma N, Okada K, Kuramoto A Cytapheresis therapy of adult T-cell leukemia: a case report. Japan J Clin Hematol 1981; 22: 885-90 (In Japanese.)
4. Imamura
SIR,-Since the signing of the Geneva Convention in 1964 doctors and nurses as well as sick and wounded have been regarded as neutrals during conflict. These principles are being brutally disregarded in El Salvador and Guatemala today. According to information obtained from Amnesty International and from other sources, military and paramilitary groups have, in recent years, assassinated, tortured, and threatened doctors, nurses, and medical students. Such armed groups have also entered hospitals and shot patients. The governments of the two countries have never punished, prosecuted, or even identified those responsible for the killings. Here are a few examples: On May 15, 1980, Dr M. A. Garcia and Dr C. E. Rodrigues were kidnapped by armed men from a hospital in Cojutepeque, El Salvador, when performing an operation. Both doctors were later found dead with clear evidence of torture. Dr C. A. Vargas Lopez was arrested by security forces when leaving his clinic in San Salvador on Dec. 16, 1981. He has not been heard of since. Dr Arnoldo Merida Zuniga was seen last when led from his clinic in Guatemala City by a group of masked, armed men, on Dec 29, 1981. Dr Filiberto Sanchez Castillo was kidnapped in Guatemala City in August, 1981. Some days later he was found dead with signs of torture and bullet wounds. I urge colleagues to write to El Salvador and Guatemala asking the governments to take vigorous action to stop violations of medical neutrality and to ensure that all health personnel can treat people in need of care without fear of reprisal. Department of Internal Medicine, Central Hospital, S-301 85 Halmstad, Sweden
LOUISE HELLQUIST
**1982 cases of abduction or arrest in El Salvador known to the Central America research department of Amnesty International include: Dr O. A. Espinoza Martinez (Feb. 5); Dr Manuel de Paz Villata (Jan. 28); Dr R. P. Vazquez Gil (Jan. 19); and Dr H. V. Moran (February). Dr J. J. A. Hidalgo Salguero, who was abducted in Guatemala City, last September, was later found dead in the El Quiche region.-ED, L. MILD CLINICAL COURSE OF PERTUSSIS IN SWEDISH INFANTS OF TODAY
SIR,—Discussing salbutamol treatment of infants with pertussis Dr Peltola and Dr Michelsson (Feb. 6, p. 310) referred to a Swedish paper from 19701 when stating that "pertussis is most lifethreatening in infants who are less than 6 months old". However, in Sweden today not even for infants of that age is pertussis a serious disease. Despite the fact that since the mid-1970s pertussis has again become endemic in Sweden2and now has reached incidence rates approaching those of the pre-vaccination era, no child has died of pertussis since 1970. The clinical course of pertussis in Sweden has become milder. In an investigation of infants less than 6 months old with bacteriologically verified pertussis published in 19793 only 24/59 infants were admitted to hospital, in most cases for social reasons, and only 1 infant was considered as critically ill. During 1977-79, 19 000 cases of pertussis (but no deaths) were notified by district medical officers in Sweden. Sweden has a population of about 8 million so this figure is about the same as the number of notified cases in England and Wales during the same period, where 102 000 cases (and 28 deaths) were reported in a population of about 50 million. In Goteborg, where I work, I have found that in the school health records of a random sample of 743 1.
2. 3.
Strangert K. Clinical course and prognosis of whooping cough in Swedish children during the first six months of life: a study of hospitalized patients 1958-1967. Scand J Infect Dis 1970; 2: 45-48 Trollfors B, Rabo E Whooping cough in adults Br Med J 1981; 283: 696-97. Trollfors B. Clinical course of whooping cough in children younger than six months. Acta Paediatr Scand 1979; 68: 323-28
children born in 1974-nearly all of whom had had three injections of a Swedish made triple vaccine-parents had stated that 39, 4% of the children had already had pertussis when they began at school at the age of last autumn. In a similar study from the prevaccination era 48 - 9% of 2000 children born in 1949 had contracted pertussis before the age of eight years. Mass vaccination with a pertussis vaccine giving 90% immunity5 began in most parts of Sweden during the 1950s. From the middle of the 1960s more than 90% of all infants were vaccinated and pertussis became rare. The return of pertussis during the 1970s seems to have been related to changes in the production of the vaccine at the beginning of the 1970s,6which made the vaccine ineffective.2 Due to the ineffective vaccine and the present mild clinical course of pertussis in Sweden the vaccination was stopped in 1979. In view of the rare but serious neurological complications of whole cell pertussis vaccinesit was not considered appropriate to reintroduce an effective vaccine of this type. We are now eagerly awaiting the development of acellular and, it is to be hoped, nontoxic, pertussis vaccines. According to data presented at a workshop on new pertussis vaccines held at the National Institutes of Health, Bethesda in February of this year such a vaccine is now under clinical evaluation in Japan. Outpatient Department of Paediatrics, Västra Frölunda Hospital, S-421 22 Västra Frölunda, Sweden JOHN TARANGER
seven years
CLUSTER OF UNCOMMON FETAL ABNORMALITIES
SIR.—Four cases of unusual fetal abnormalities were detected at routine second trimester ultrasound examinations over a period of 18 days, during December, 1981, and January, 1982. All four pregnancies were terminated, and necropsy revealed remarkably similar features in all four cases (table). Genetic consultation with Prof. C. O. Carter suggests a risk of approximately 1 such abnormality in 20 000 births, and their chronological and geographical occurrence led to a search for common associations. None have been found to date and no further such cases are known to have occurred locally. During the 18 day period in question 596 ultrasound examinations were done, giving an incidence ofin 189, if the case is discounted. Since not all pregnant women are subjected to ultrasound examinations, further cases of these abnormalities may come to light 4. Ström J. Social development and declining incidence of some common epidemic diseases in children: a study of the incidence in different age groups in Stockholm. Acta Paediatr Scand 1967, 56: 159-63 5. Laurell G, Mellbin T, Rabo E, Vahlquist B, Zetterquist P. Systematische Impfung mit kombiniertem Impstoff (Diphterie, Tetanus, Pertussis) im Säuglingsalter. Serologische und klinische Studien. Klin Wochenschr 1957; 35: 920-24 6. Askelöf P Statement of the effect of various methods for inactivating pertussis vaccines In: Manclark CR, Hill JC, eds. International symposium on pertussis: DHEW (NIH) 79-1830. Washington, DC: US Government Printing Office, 1979: 368-69. 7. Miller DL, Ross EM, Alderslade R, Bellman M, Rawson NSB. Pertussis immunisation and serious acute neurological illness in children. Br Med J 1981, 282: 1595-99.
POST MORTEM FINDINGS OF ABNORMAL FETUSES
*This fetus also had patent "cord" between bladder neck and rectum;
no
bifurcation of
aorta; and gut malrotation.
Hypopl.=hypoplastic; hydronephr.=hydronephrosis; imperf. =imperforate; perf =perforate.
cyst. dyspl. = cysuc
dysplasia;
1361
during the next few months. The last normal menstrual periods of the four patients concerned were between Aug. 24 and Sept. 22, 198 L In the absence of any further cases, these 4 should probably be regarded as fortuitous. If other cases occur, however, a diligent search for a causative factor will be needed. Would obstetricians and pathologists notify me if they find a case with the abnormalities as tabulated? Institute of Obstetrics and
Gynaecology, Queen Charlotte’s Maternity Hospital,
M. J. BENNETT
London W6 0XG
ENALAPRIL (MK-421) AND THE WHITE CELL COUNT AND HAEMATOCRIT
SIR,-In response to the recent report of reversible leukopenia associated with MK-421 (enalapril maleate),! we would like to report our experience with complete blood counts and lack of association of leukopenia during a study of MK-421. MK-421 is a new, non-sulphydryl angiotensin-converting enzyme inhibitor which theoretically should be devoid of the penicillamine-like reactions associated with captopril, including rash, fever, proteinuria, neutropenia, and agranulocytosis.2,3 In the present prospective study, thirty normal and hypertensive volunteers received one of three medications: hydrochlorthiazide (HCTZ, 50 mg/day), MK-421(10 mg/day), or HCTZ (50 mg/day) plus MK-421I (10 mg/day) over 4-60 weeks. Blood studies were done regularly for multiple analyses, including complete blood counts. Results of the white count and haematocrit are shown in the table. WHITE CELL COUNTS AND HAEMATOCRITS IN PATIENTS ON HYDROCHLOROTHIAZIDE
(HCTZ),
ENALAPRIL
(MK-421), OR BOTH
*p<0-05.
has been demonstrated to increase plasma levels in normal and anephric rats before and after stimulation by either hypoxia or anaemia.5,6 Since the effect of converting enzyme blockade on erythropoietin levels remains to be studied in man it is impossible to know whether converting-enzyme inhibitors such as MK-421 could impair the erythropoietic response to stimuli like anaemia or hypoxia. In the limited experience afforded by this study, leukopenia or immunologically related syndromes appear to be very unusual with MK-421. After phlebotomy, a small decline in the haematocrit was ,seen in the two groups receiving MK-421 but not in the HCTZ alone group. This change was small, however, and does not constitute proof of a cause-and-effect relationship. In summary, MK-421 appeared to have few, if any, adverse haematological effects; however, careful haematological monitoring will be required until further data are available.
angiotensin-l! infusion
erythropoietin
Section
of Endocrinology and Metabolism, University Hospital,
GEORGE T. GRIFFING MELBY
JAMES C.
Boston, Massachusetts 02118, U.S.A.
T-CELL LEUKAEMIA A FEW MONTHS APART IN TWO BROTHERS
SIR,-Since adult T-cell leukaemia (ATL) was reported by Uchiyama et al.,111 out of 102 patients with ATL have revealed a family history of malignant lymphoma or leukaemia.2Here, we report a family of six siblings, of whom two men developed ATL almost simultaneously. A 51-year-old man was admitted to another hospital in December 1979, because of a 1 month history of heavy head sensation and anorexia. He had moderate hepatomegaly with some systemic lymphadenopathy. Hb 11-55 g/dl, platelets 54 x 109/1, and white blood cells 7 - 3 x 109/1 with 2% erythroblasts. Hypercalcaemia mmol, which is frequently seen in ATL, was noted among the laboratory data. Biopsy of a lymph node in the neck revealed malignant lymphoma, mixed type, diffuse. It was also diagnosed as diffuse lymphoma, pleomorphic type, according to the new classification in Japan (Lymphoma Study Group Classification),3 which is a usual feature ofATL. Combination chemotherapy ofvincristine (1-00 mg weekly) and prednisolone (20 mg daily) resulted in a poor response by malignant cells. The patient died of bleeding in March, 1980. The 60-year-old brother of the above patient was admitted to our hospital in April, 1980, complaining of facial oedema and exanthema of the skin with an itchy sensation. He had moderate hepatosplenomegaly and some systemic lymphadenopathy. Hb 14-3g/dl, platelets 194 x 109/1, and WBC 215 x 109/1, 95% of the cells being typical ATL. Bone marrow aspirate contained 74-8% of cells of similar morphology. 90% of leucocytes formed sheep red-blood-cell rosettes, 93% possessed T-cell surface antigen of peripheral T-cell type, and none of the leukaemic cells had TdT or common ALL antigens. None of the leukaemic cells possessed B-cell markers (SmIg, CIg, Ia-like antigen, or EAC receptors). The leukaemic cells also possessed OKT3, OKT8, and Tac antigens on their cell surfaces. The HLA haplotype was HLA A3,26,B44,-,C3,-. A diagnosis of ATL was supported by lymph node biopsy which revealed malignant lymphoma, diffuse, pleomorphic type (Lymphoma Study Group Classification. Leukapheresis and combination chemotherapy resulted in rapid and sustained clinical improvement.4 After 13 months of complete remission, the patient -
Although the WCC tended to decrease with the onset of therapy, this was insignificant in all three groups. Only two subjects had WCC counts below 4000 cells/1: one patient in the MK-421 group had an asymptomatic decrease from 6000 to 3900 /J.11 during the first week of treatment, and a patient on HCTZ group had a decrease from 4100 to 3600 during the first week (the nadir was 3000 and the WCC subsequently rose to 6300 cells/1). The leukopenia in both of these patients is probably related to phlebotomy (1300 ml over 33 days), since they had an associated fall in haematocrit of 49% to 41 % and 38% to 33%, respectively. Furthermore, they had no symptoms or manifestations of leukopenia or immune-related disease. There was a small but significant decrease in haematocrit in the MK-421 and HCTZ + MK-421 groups, but not the HCTZ group. The lack of a significant haematocrit decline in the HCTZ group could be due to diuretic-induced volume contraction and haemoconcentration, but this may not be. an adequate explanation, since the HCTZ + MK-421 group had evidence of greater volume contraction, reflected in a larger weight loss (2 - 3 vs 1 -6 kg) and a greater sodium deficit (251 vs 87 mmol) at day 7 and persisting up to day 28. It is impossible, in the present study, to explain fully or appreciate the significance of the slight differences in haematocrits, but it cannot be excluded that MK-421 was a contributing factor. It has been reported that angiotensin-II is necessary for maximal erythropoietin elaboration in certain animal models.4Subpressor 1. Studen
2. 3. 4.
A, Vetter W. Reversible leukopenia associated with angiotensin-converting inhibitor, MK-421. Lancet 1982; i: 458 Vidt DG, Bravo EL, Fouad FM. Captopril. N EnglJ Med 1982; 306: 214-19. van Brummelen P, Willemze R, Ran WD, Thompson J. Captopril-associated agranulocytosis. Lancet 1980; i: 150. Anagnostou A, Baranowski R, Pillay VKG, Kurtzman N, Vercellotti G, Fried W. Effect of renin on extra renal erythropoietin production. J Lab Clin Med 1976; 88: 707-18.
5. Gould
AB, Goodman S, DeWolf R,
et
al. Interrelation of the
renin
system and
J Lab Clin Med 1980; 96: 523-33 6. Fried W, Barone-Varelas J, Barone T, Anagnostou A. Effect ofangiotensin infusion on extra renal erythropoitin production J Lab Clin Med 1982, 99: 520-25. I Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H Adult T-cell leukemia:
erythropoietin
in
rats.
clinical and hematologic features of 16 cases. Blood 1977; 50: 481-92. 2 The T- and B-cell Malignancy Study Group. Statistical analysis of immunologic, clinical and histopathologic data on lymphoid malignancies in Japan Japan J Clin
Oncol 1981; 11: 15-38. T, Tajima K, Nanba K,
et al Some problems on the histopathological diagnosis of non-Hodgkin’s malignant lymphoma. a proposal of a new type. Acta Pathol Jap
3. Suchi
1979, 29: 755-76. N, Tokumo K, Koganemaru S, Oguma N, Okada K, Kuramoto A Cytapheresis therapy of adult T-cell leukemia: a case report. Japan J Clin Hematol 1981; 22: 885-90 (In Japanese.)
4. Imamura