- Email: [email protected]
Risk of latrogenic fetal infection at prenatal diagnosis
Clostridium difficile diarrhoea and rifabutin SIR—We were
surprised by McBride and colleagues’ findings (Feb 12, p 417). We use rifabutin extensively for both prophylaxis and therapy of Mycobacterium avium complex infection (MAI) and we have not encountered Clostridium difficile associated diarrhoea in any patient exclusively receiving rifabutin. All HIV-seropositive patients who develop diarrhoea while in hospital and who are on antibiotics are tested for C difficile toxin. Between March, 1993, and February, 1994, 12 of 186 tests were positive for C difficile. 7 of these 12 patients had diarrhoea severe enough to warrant treatment with oral vancomycin. During the same time period 111 patients were treated with rifabutin 300—450 mg a day for at least a month and in only 2 did C difficile associated diarrhoea develop. All 12 patients had received other antibiotic agents, well known to be linked to C difficile associated diarrhoea, in the 2 weeks before symptoms developed. The patients described by McBride et al were on treatment for MAI. One agent commonly used in combination is clarithromycin, which has been reported to cause pseudomembranous colitis.1 Our data do not support the view that rifabutin is a common cause of C difficile associated diarrhoea in HIV seropositive patients.
histological picture was characterised by diffuse effacement of the normal structure and infiltration of a composite lymphoma with medium to large pleomorphic T cells intermingled with large atypical CD20-positive blast cells, which frequently resembled Hodgkin and Reed-Sternberg cells. PCR analysis revealed clonal rearrangements of TCR and IgH genes, consistent with the diagnosis of composite lymphoma. In-situ hybridisation nuclear signals for EBER probes and LMP immunostaining were positive in the large atypical B blasts. The malignant B-cell lymphomas in both patients were associated with EBV. Since the virus is present in reactive B cells in peripheral T-cell lymphomas of both AILD and pleomorphic types, large-cell B lymphomas may have arisen from EBV-immortalised B-cell clones. In the case of the lymphoma developing after diagnosis and treatment of AILD, the inherent immunosuppression of the disease or the transient suppression of the immune system after treatment may have facilitated the establishment of the secondary B-cell clone similar to the occurrence of monoclonal or polyclonal
lymphoproliferations in other immunodeficiency states. German Ott, M Michaela Ott, Hans-Konrad Müller-Hermelink Department of Pathology, University of Würzburg, D-97080 Würzburg, Germany 1
R C G Pollock, D C Shanson, M Nelson, PJ Neild, B G Gazzard 2
Chelsea and Westminster Hospital, London SW10 9NH, UK
1
Braegger CP, Nadal D. Clarithromycin and pseudomembranous enterocolitis. Lancet 1944; 343: 241.
Ott G, Ott MM, Feller AC, et al. Prevalence of Epstein-Barr virus DNA in different T-cell lymphoma entities in a European population. Int J Cancer 1992; 51: 562-67. Korbjuhn P, Anagnostopoulos I, Hummel M, et al. Frequent latent Epstein-Barr virus infection of neoplastic T cells and bystander B cells in human immunodeficiency virus-negative European peripheral pleomorphic T-cell lymphomas. Blood 1993; 82: 217-23.
Risk of latrogenic fetal infection at prenatal
Epstein—Barr virus, B cells, T cells, and lymphoproliferative disorder
a
SiR-In
angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD), the finding of clonal T-cell receptor rearrangements in most cases justifies the classification of AILD as a peripheral T-cell lymphoma (updated Kiel
classification). Peripheral T-cell lymphoma of AILD type and pleomorphic T-cell lymphoma are often associated with the Epstein-Barr virus (EBV).1 In-situ hybridisation with simultaneous demonstration of the immunophenotype revealed that the virus resided in neoplastic T cells and in bystander B cells.:! Because of the puzzling occurrence of secondary high-grade B-cell lymphomas in AILD, we questioned whether EBV might be aetiologically related to the development of these neoplasms. We studied two patients in whom a high grade B-cell lymphoma was combined with pre-existing AILD in one case and occurred simultaneously with a pleomorphic T-cell lymphoma in the other. The first patient was a 50-year-old man who was diagnosed with AILD in 1989. He was treated with chemotherapy and radiation followed by autologous bone marrow transplantation. In 1991 and 1992, cervical lymph nodes were excised, which showed a proliferation of atypical blast cells resembling immunoblasts. Immunophenotyping showed them to be of B-cell lineage and polymerase-chain-reaction (PCR) analysis of immunoglobulin heavy chain and T-cell receptor (TCR) genes yielded a germline pattern for the TCR genes and clonal rearrangement of B-cells in the node excised in 1991. In-situ hybridisation with EBV-specific non-coding small RNAs (EBERs) as well as immunostaining for the latent membrane protein (LMP) disclosed EBV in all tumour cells. The second patient was a 25-year-old man with a generalised neurodermatitis. He had enlargements of inguinal, abdominal, and retroperitoneal lymph nodes. In addition, an epidural tumour was removed after relevant diagnostic procedures. The a
922
diagnosis SIR—Invasive procedures for prenatal diagnosis such as chorionic villus sampling (CVS) or amniocentesis are associated with a risk of introducing maternal blood into the fetal circulation, with the possibility of transmitting a maternal infection to an uninfected fetus. Several cases of bacterial infection have been reported after transcervical CVS.1.2 To our knowledge, no case of viral infection after transabdominal sampling has been reported, although the theoretical possibility of transferring viral infections during invasive procedures for prenatal diagnosis has been mentioned.3,4 We report two cases of fetal infection diagnosed by polymerasechain-reaction (PCR) methods during pregnancy. A 28-year-old woman, 18 weeks pregnant, was referred to our ultrasound unit in April, 1993. She had undergone prenatal diagnosis elsewhere for the detection of Toxoplasma gondii in villi and amniotic fluid at 15 weeks because of the presence of specific IgM in maternal serum; the tests were positive with PCR in maternal serum, and negative in the fetal compartments. The ultrasound scan at 18 weeks, however, revealed hydrocephalus. The patient decided to continue the pregnancy to term. Neonatal samples tested positive for T
gondii. A 39-year-old woman, at 17 weeks’ gestation, had prenatal diagnosis with PCR on villi and amniotic fluid because of evidence of maternal seroconversion for cytomegalovirus; villi and amniotic fluid tested negative for the virus, whereas maternal serum was positive. 2 weeks later, hydrocephalus was evident on ultrasound. The patient preferred to terminate her pregnancy elsewhere. The abortive material tested positive for cytomegalovirus We speculate that, in both cases, the infectious agent was transmitted to the fetus at the time of the invasive diagnostic procedure. Indiscriminate use of invasive procedures for prenatal diagnosis may transmit infectious agents to a
previously uninfected fetus through an interruption protective barrier of the placenta and membranes.
of the
Claudio Giorlandino, Elena Bilancioni, Paolo D’Alessio, Ludovico Muzii Artemisia Medical Center, Viale Liegi 49, 00168 Rome, Italy; and Department of Obstetrics and Gynaecology, Universita’ Cattolica del Sacro Cuore, Rome
1 Garden AS, Reid G, Benzie RJ. Chorionic villus sampling. Lancet 1985; i: 1269-70. 2 Barela AI, Kleinman GE, Golditch IM, Menke DJ, Hogge A,
Septic shock with renal failure after chorionic villus sampling. Am J Obstet Gynaecol 1986; 154: 1100-02. Catanzarite V, Dankner WM. Prenatal diagnosis of congenital cytomegalovirus infection: false-negative amniocentesis at 20 weeks’ gestation. Prenat Diagn 1993; 13: 1021-25. Towers CV, Chinn DH, Asrat T, Miller EI, Freeman RK. Intraamniotic bleeding following transabdominal amniocentesis. J Maternal Fetal Med 1993; 2: 133-37. Golbus MS.
3
4
Folic acid, pernicious anaemia, and of neural tube defects
prevention
SIR—We agree with Wald and Bower (Feb 5, p 307) that fortification of foods with folic acid, as recommended by the UK and US governments, should be instituted without delay and that the concern about vitamin B12 deficiency neuropathy being precipitated by folate administration should not limit public health measures designed to prevent neural tube defects (NTD). However, although the UK Medical Research Council vitamin study showed that folic acid supplementation could prevent nearly three-quarters’ of such defects,! it cannot prevent all of them; nor are we convinced that folic acid deficiency is the aetiological factor in all NTD. One of us (JBS) reported a cluster of NTD in northern India after an epidemic of dengue fever. A high incidence of NTD in north India is well known.3 The incidence varies between 4-11 and 12.0 per 1000 (mean 71) compared with 05 in the east (Calcutta), 22 in the west (Bombay), 2-3 in the south (Madras), and 3 96 in central India (Wardha).2 Since dengue fever is rampant in north India and much less common in the rest of the country, we believe it could be a teratogen, causing at least some cases of NTD. North India (especially Punjab) is more prosperous than the rest of India and the diet is more nutritious, with folate levels no less than those of people elsewhere in India. Anwar et al4 found serum from pregnant women carrying a fetus with NTD to be teratogenic for rat embryos in culture, suggesting an infectious aetiology for NTD. Isolated cases of NTD are believed to be multifactorial, involving a genetic (polygenic) predisposition and the possible interaction of environmental factors, which together result in abnormal morphogenesis of the nervous system.5 A decreasing incidence of NTD at birth is also partly due to screening. While folate deficiency is probably responsible for most NTD, routine folate supplementation will not prevent every case. J B Sharma, M R B Newman, R J Smith Kettering and District General Hospital, Kettenng NN16 8UZ, UK 1 2
3 4
5
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the MRC Vitamin Study. Lancet 1991; 338: 132-37. Sharma JB, Gulati N. Potential relationship between dengue fever and neural tube defects in a northern district of India. Int J Gynecol Obstet 1992; 39: 291-95. Verma IC. High incidence of neural tube defects in north India. Lancet 1978; i: 879. Anwar M, MacVicar J, Beck F. Serum from pregnant women carrying fetus with neural tube defect is teratogenic for rat embryos in culture. Br J Obstet Gynaecol 1989; 96: 33-36. Adams RD, Victor M. Principles of neurology, 4th ed. New York: McGraw-Hill, 1989: 976.
Chemokines SIR—Pattison and colleagues (Jan 22, p 209) and McLean’s accompanying commentary draw attention to chemokines, a new superfamily of cytokines involved in various disease processes, ranging from inflammation to atherosclerosis and neoplasia.1,2 The study of chemokines is inherently complex and confusing, at times even for people in the field, because of the considerable number of mediators, overlapping spectrum of action, promiscuous use of receptors, and irrational nomenclature. Unfortunately, the McLean’s commentary contains serious flaws which may increase confusion. Specifically, it is not true that the interleukin (IL)-8 type-II receptor (or B), in addition to the cysteine (C)-X-C chemokines neutrophil activating protein (NAP)-2 and melanoma growthstimulating activity (MGSA), also binds the C-C chemokines macrophage chemotactic protein (MCP)-l and RANTES (regulated upon activation, normal T cell expressed and secreted). It is also not true that the second receptor is identical to the Duffy erythrocyte antigen. The latter is a distinct promiscuous chemokine receptor of unknown function expressed in erythroid differentiation.3,4 Finally, although the generic names intercrines and Scy have been used in the past, 2 years ago agreement was reached by several investigators (including proponents of the above names) on the term chemokines, which has rapidly gained general acceptance and usage. Resurrecting old alternatives does not help the unaccustomed reader, who is probably already confused by an unsatisfactory and irrational nomenclature. Alberto Mantovani, Silvano Sozzani Istituto di Ricerche
1
2
3
4
Farmacologiche "Mario Negri", 20157 Milano, Italy
Oppenheim JJ, Zachariae CO, Mukaida N, Matsushima K. Properties of the novel proinflammatory supergene "intercrine" family. Ann Rev Immunol 1991; 9: 617-48. Mantovani A, Bottazzi B, Colotta F, Sozzani S, Ruco L. The origin and function of tumor-associated macrophages. Immunol Today 1992; 13: 265-70. Horuk R, Chitnis CE, Darbonne WC, et al. A receptor for the malarial parasite Plasmodium vivax—the erythrocyte chemokine receptor. Science 1993; 261: 1182-84. Chaudhuri A, Polykova J, Zbrzezna V, Williams K, Gulati S, Pogo O. Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and receptor for the Plasmodium vivax malaria parasite. Proc Natl Acad Sci USA 1993; 90: 10793-97.
Plasma factors and disturbance of endothelial function in pre-eclampsia SIR—A good hypothesis explains and unifies existing data to a greater extent than previous hypotheses, and it makes more precise and novel predictions.1 By these criteria Arbogast and
colleagues’ hypothesis (Feb 5, p 340) disappoints. They postulate that an imbalance between the toxic effect of very-low-density lipoproteins (VLDL) and the protective effect of toxicity-preventing activity (TxPa; the pI 56 form of plasma albumin) leads to endothelial dysfunction in preeclampsia. They review traditional treatments for pre-eclampsia (bed rest, sedation, glucose infusions, high protein diets, and albumin infusions), and make tenuous links between these treatments and the ratio of TxPa to VLDL. Unfortuntely, the relevance of this historical resume to their hypothesis is unclear since the treatments listed (with the possible exception of bed rest) have either been discredited or are unsupported by evidence of efficacy from randomised controlled trials.2 Surprisingly, treatments regarded as promising, which are 923
surprised by McBride and colleagues’ findings (Feb 12, p 417). We use rifabutin extensively for both prophylaxis and therapy of Mycobacterium avium complex infection (MAI) and we have not encountered Clostridium difficile associated diarrhoea in any patient exclusively receiving rifabutin. All HIV-seropositive patients who develop diarrhoea while in hospital and who are on antibiotics are tested for C difficile toxin. Between March, 1993, and February, 1994, 12 of 186 tests were positive for C difficile. 7 of these 12 patients had diarrhoea severe enough to warrant treatment with oral vancomycin. During the same time period 111 patients were treated with rifabutin 300—450 mg a day for at least a month and in only 2 did C difficile associated diarrhoea develop. All 12 patients had received other antibiotic agents, well known to be linked to C difficile associated diarrhoea, in the 2 weeks before symptoms developed. The patients described by McBride et al were on treatment for MAI. One agent commonly used in combination is clarithromycin, which has been reported to cause pseudomembranous colitis.1 Our data do not support the view that rifabutin is a common cause of C difficile associated diarrhoea in HIV seropositive patients.
histological picture was characterised by diffuse effacement of the normal structure and infiltration of a composite lymphoma with medium to large pleomorphic T cells intermingled with large atypical CD20-positive blast cells, which frequently resembled Hodgkin and Reed-Sternberg cells. PCR analysis revealed clonal rearrangements of TCR and IgH genes, consistent with the diagnosis of composite lymphoma. In-situ hybridisation nuclear signals for EBER probes and LMP immunostaining were positive in the large atypical B blasts. The malignant B-cell lymphomas in both patients were associated with EBV. Since the virus is present in reactive B cells in peripheral T-cell lymphomas of both AILD and pleomorphic types, large-cell B lymphomas may have arisen from EBV-immortalised B-cell clones. In the case of the lymphoma developing after diagnosis and treatment of AILD, the inherent immunosuppression of the disease or the transient suppression of the immune system after treatment may have facilitated the establishment of the secondary B-cell clone similar to the occurrence of monoclonal or polyclonal
lymphoproliferations in other immunodeficiency states. German Ott, M Michaela Ott, Hans-Konrad Müller-Hermelink Department of Pathology, University of Würzburg, D-97080 Würzburg, Germany 1
R C G Pollock, D C Shanson, M Nelson, PJ Neild, B G Gazzard 2
Chelsea and Westminster Hospital, London SW10 9NH, UK
1
Braegger CP, Nadal D. Clarithromycin and pseudomembranous enterocolitis. Lancet 1944; 343: 241.
Ott G, Ott MM, Feller AC, et al. Prevalence of Epstein-Barr virus DNA in different T-cell lymphoma entities in a European population. Int J Cancer 1992; 51: 562-67. Korbjuhn P, Anagnostopoulos I, Hummel M, et al. Frequent latent Epstein-Barr virus infection of neoplastic T cells and bystander B cells in human immunodeficiency virus-negative European peripheral pleomorphic T-cell lymphomas. Blood 1993; 82: 217-23.
Risk of latrogenic fetal infection at prenatal
Epstein—Barr virus, B cells, T cells, and lymphoproliferative disorder
a
SiR-In
angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD), the finding of clonal T-cell receptor rearrangements in most cases justifies the classification of AILD as a peripheral T-cell lymphoma (updated Kiel
classification). Peripheral T-cell lymphoma of AILD type and pleomorphic T-cell lymphoma are often associated with the Epstein-Barr virus (EBV).1 In-situ hybridisation with simultaneous demonstration of the immunophenotype revealed that the virus resided in neoplastic T cells and in bystander B cells.:! Because of the puzzling occurrence of secondary high-grade B-cell lymphomas in AILD, we questioned whether EBV might be aetiologically related to the development of these neoplasms. We studied two patients in whom a high grade B-cell lymphoma was combined with pre-existing AILD in one case and occurred simultaneously with a pleomorphic T-cell lymphoma in the other. The first patient was a 50-year-old man who was diagnosed with AILD in 1989. He was treated with chemotherapy and radiation followed by autologous bone marrow transplantation. In 1991 and 1992, cervical lymph nodes were excised, which showed a proliferation of atypical blast cells resembling immunoblasts. Immunophenotyping showed them to be of B-cell lineage and polymerase-chain-reaction (PCR) analysis of immunoglobulin heavy chain and T-cell receptor (TCR) genes yielded a germline pattern for the TCR genes and clonal rearrangement of B-cells in the node excised in 1991. In-situ hybridisation with EBV-specific non-coding small RNAs (EBERs) as well as immunostaining for the latent membrane protein (LMP) disclosed EBV in all tumour cells. The second patient was a 25-year-old man with a generalised neurodermatitis. He had enlargements of inguinal, abdominal, and retroperitoneal lymph nodes. In addition, an epidural tumour was removed after relevant diagnostic procedures. The a
922
diagnosis SIR—Invasive procedures for prenatal diagnosis such as chorionic villus sampling (CVS) or amniocentesis are associated with a risk of introducing maternal blood into the fetal circulation, with the possibility of transmitting a maternal infection to an uninfected fetus. Several cases of bacterial infection have been reported after transcervical CVS.1.2 To our knowledge, no case of viral infection after transabdominal sampling has been reported, although the theoretical possibility of transferring viral infections during invasive procedures for prenatal diagnosis has been mentioned.3,4 We report two cases of fetal infection diagnosed by polymerasechain-reaction (PCR) methods during pregnancy. A 28-year-old woman, 18 weeks pregnant, was referred to our ultrasound unit in April, 1993. She had undergone prenatal diagnosis elsewhere for the detection of Toxoplasma gondii in villi and amniotic fluid at 15 weeks because of the presence of specific IgM in maternal serum; the tests were positive with PCR in maternal serum, and negative in the fetal compartments. The ultrasound scan at 18 weeks, however, revealed hydrocephalus. The patient decided to continue the pregnancy to term. Neonatal samples tested positive for T
gondii. A 39-year-old woman, at 17 weeks’ gestation, had prenatal diagnosis with PCR on villi and amniotic fluid because of evidence of maternal seroconversion for cytomegalovirus; villi and amniotic fluid tested negative for the virus, whereas maternal serum was positive. 2 weeks later, hydrocephalus was evident on ultrasound. The patient preferred to terminate her pregnancy elsewhere. The abortive material tested positive for cytomegalovirus We speculate that, in both cases, the infectious agent was transmitted to the fetus at the time of the invasive diagnostic procedure. Indiscriminate use of invasive procedures for prenatal diagnosis may transmit infectious agents to a
previously uninfected fetus through an interruption protective barrier of the placenta and membranes.
of the
Claudio Giorlandino, Elena Bilancioni, Paolo D’Alessio, Ludovico Muzii Artemisia Medical Center, Viale Liegi 49, 00168 Rome, Italy; and Department of Obstetrics and Gynaecology, Universita’ Cattolica del Sacro Cuore, Rome
1 Garden AS, Reid G, Benzie RJ. Chorionic villus sampling. Lancet 1985; i: 1269-70. 2 Barela AI, Kleinman GE, Golditch IM, Menke DJ, Hogge A,
Septic shock with renal failure after chorionic villus sampling. Am J Obstet Gynaecol 1986; 154: 1100-02. Catanzarite V, Dankner WM. Prenatal diagnosis of congenital cytomegalovirus infection: false-negative amniocentesis at 20 weeks’ gestation. Prenat Diagn 1993; 13: 1021-25. Towers CV, Chinn DH, Asrat T, Miller EI, Freeman RK. Intraamniotic bleeding following transabdominal amniocentesis. J Maternal Fetal Med 1993; 2: 133-37. Golbus MS.
3
4
Folic acid, pernicious anaemia, and of neural tube defects
prevention
SIR—We agree with Wald and Bower (Feb 5, p 307) that fortification of foods with folic acid, as recommended by the UK and US governments, should be instituted without delay and that the concern about vitamin B12 deficiency neuropathy being precipitated by folate administration should not limit public health measures designed to prevent neural tube defects (NTD). However, although the UK Medical Research Council vitamin study showed that folic acid supplementation could prevent nearly three-quarters’ of such defects,! it cannot prevent all of them; nor are we convinced that folic acid deficiency is the aetiological factor in all NTD. One of us (JBS) reported a cluster of NTD in northern India after an epidemic of dengue fever. A high incidence of NTD in north India is well known.3 The incidence varies between 4-11 and 12.0 per 1000 (mean 71) compared with 05 in the east (Calcutta), 22 in the west (Bombay), 2-3 in the south (Madras), and 3 96 in central India (Wardha).2 Since dengue fever is rampant in north India and much less common in the rest of the country, we believe it could be a teratogen, causing at least some cases of NTD. North India (especially Punjab) is more prosperous than the rest of India and the diet is more nutritious, with folate levels no less than those of people elsewhere in India. Anwar et al4 found serum from pregnant women carrying a fetus with NTD to be teratogenic for rat embryos in culture, suggesting an infectious aetiology for NTD. Isolated cases of NTD are believed to be multifactorial, involving a genetic (polygenic) predisposition and the possible interaction of environmental factors, which together result in abnormal morphogenesis of the nervous system.5 A decreasing incidence of NTD at birth is also partly due to screening. While folate deficiency is probably responsible for most NTD, routine folate supplementation will not prevent every case. J B Sharma, M R B Newman, R J Smith Kettering and District General Hospital, Kettenng NN16 8UZ, UK 1 2
3 4
5
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the MRC Vitamin Study. Lancet 1991; 338: 132-37. Sharma JB, Gulati N. Potential relationship between dengue fever and neural tube defects in a northern district of India. Int J Gynecol Obstet 1992; 39: 291-95. Verma IC. High incidence of neural tube defects in north India. Lancet 1978; i: 879. Anwar M, MacVicar J, Beck F. Serum from pregnant women carrying fetus with neural tube defect is teratogenic for rat embryos in culture. Br J Obstet Gynaecol 1989; 96: 33-36. Adams RD, Victor M. Principles of neurology, 4th ed. New York: McGraw-Hill, 1989: 976.
Chemokines SIR—Pattison and colleagues (Jan 22, p 209) and McLean’s accompanying commentary draw attention to chemokines, a new superfamily of cytokines involved in various disease processes, ranging from inflammation to atherosclerosis and neoplasia.1,2 The study of chemokines is inherently complex and confusing, at times even for people in the field, because of the considerable number of mediators, overlapping spectrum of action, promiscuous use of receptors, and irrational nomenclature. Unfortunately, the McLean’s commentary contains serious flaws which may increase confusion. Specifically, it is not true that the interleukin (IL)-8 type-II receptor (or B), in addition to the cysteine (C)-X-C chemokines neutrophil activating protein (NAP)-2 and melanoma growthstimulating activity (MGSA), also binds the C-C chemokines macrophage chemotactic protein (MCP)-l and RANTES (regulated upon activation, normal T cell expressed and secreted). It is also not true that the second receptor is identical to the Duffy erythrocyte antigen. The latter is a distinct promiscuous chemokine receptor of unknown function expressed in erythroid differentiation.3,4 Finally, although the generic names intercrines and Scy have been used in the past, 2 years ago agreement was reached by several investigators (including proponents of the above names) on the term chemokines, which has rapidly gained general acceptance and usage. Resurrecting old alternatives does not help the unaccustomed reader, who is probably already confused by an unsatisfactory and irrational nomenclature. Alberto Mantovani, Silvano Sozzani Istituto di Ricerche
1
2
3
4
Farmacologiche "Mario Negri", 20157 Milano, Italy
Oppenheim JJ, Zachariae CO, Mukaida N, Matsushima K. Properties of the novel proinflammatory supergene "intercrine" family. Ann Rev Immunol 1991; 9: 617-48. Mantovani A, Bottazzi B, Colotta F, Sozzani S, Ruco L. The origin and function of tumor-associated macrophages. Immunol Today 1992; 13: 265-70. Horuk R, Chitnis CE, Darbonne WC, et al. A receptor for the malarial parasite Plasmodium vivax—the erythrocyte chemokine receptor. Science 1993; 261: 1182-84. Chaudhuri A, Polykova J, Zbrzezna V, Williams K, Gulati S, Pogo O. Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and receptor for the Plasmodium vivax malaria parasite. Proc Natl Acad Sci USA 1993; 90: 10793-97.
Plasma factors and disturbance of endothelial function in pre-eclampsia SIR—A good hypothesis explains and unifies existing data to a greater extent than previous hypotheses, and it makes more precise and novel predictions.1 By these criteria Arbogast and
colleagues’ hypothesis (Feb 5, p 340) disappoints. They postulate that an imbalance between the toxic effect of very-low-density lipoproteins (VLDL) and the protective effect of toxicity-preventing activity (TxPa; the pI 56 form of plasma albumin) leads to endothelial dysfunction in preeclampsia. They review traditional treatments for pre-eclampsia (bed rest, sedation, glucose infusions, high protein diets, and albumin infusions), and make tenuous links between these treatments and the ratio of TxPa to VLDL. Unfortuntely, the relevance of this historical resume to their hypothesis is unclear since the treatments listed (with the possible exception of bed rest) have either been discredited or are unsupported by evidence of efficacy from randomised controlled trials.2 Surprisingly, treatments regarded as promising, which are 923