1067
We agree with Goesch and colleagues about the risk of transfer of P carinii between immunosuppressed patients. Moreover, there is laboratory evidence to support such transfer.4 Despite the lack of official guidelines5 patients with active PCP should be isolated. TH. BENSOUSAN B. GARO S. ISLAM B. BOURBIGOT J. CLEDES M. GALE
Departments of Intensive Care and Infectious Diseases and Nephrology and Renal Transplantation, University Hospital of Brest, 29285 Brest, France
1.Gajdusek
DC.
Pneumocystis carinii: aetiologic agent with interstitial plasma cell
pneumonia of premature and young infants. Pediatrics 1957; 19: 543-65. 2. Hardy
AP, Wajszczuk CP, Suffredini AF, Hakala TR, Monto HO. Pneumocystis m renal transplant recipients treated with cyclosporine and
carinii pneumonia
steroids. J Infect Dis 1984; 149: 143-47. 3. Ferec C, Bourbigot B, Verlingue C, et al. Circadian variation of lymphocyte subsets after renal transplantation. Transplant Proc 1986; 18: 1308-10. 4. Hughes WT. Natural mode of acquisition for de novo infection with Pneumocystis carinii. J Infect Dis 1982; 145: 842-48. 5. Walzer PD. Pneumocystis carinii: principles and practice of infectious diseases. New York: Churchill Livingstone, 1990: 2103-10.
Infection of human T cells with mycoplasma, inhibition of CD4 expression and HIV-1 gp120 glycoprotein binding, and
infectivity SIR,-Myocoplasma species have been shown to influence HIV-1I growth in human T-cell lines. Introduction of mycoplasma to cultures depresses HIV-1 replication as measured by reverse transcriptase (RT) activity, and treatment of HIV-1 infected T cells with antimycoplasma tetracyclines causes an increase in RT activity.1,2 Mycoplasmas are known to be mitogenic for human T and B cells,3.4 and killed mycoplasma can stimulate HIV-1 p24 antigen production in T-cell lines.s We have shown that a glucose-fermenting mycoplasma, isolated from lymphoid cells of an HIV-1 infected patient with AIDS-related complex, affects the HIV-1 envelope receptor CD46’ expression by T cells. Infection of the human T-cell line CEM8 with this organism led to a specific reduction in the expression of CD4, accompanied by a decrease in binding of the HIV-1 envelope protein gpl20. CEM cells were infected with mycoplasma and observed for 3 weeks during which time mycoplasma infection was monitored by electronmicroscopy and by DNA staining.9 Cell surface expression of CD4 and gp 120 binding were first examined 3 days after mycoplasma infection. Cells were reacted with monoclonal antibodies to CD4 (Leu 3a/3b) or CD5 (Leu 1), a cell surface molecule on CEM unrelated to HIV binding, and compared with uninfected CEM. The expression of each surface antigen was tested in quadruplicate and then analysed in triplicate by flow cytometry (’Facscan’, Becton Dickinson). CD4
and CD5were measured as the median channel of the fluorescence histograms. Differences between these values were assessed with Student’s t-test. To measure gpl20 binding, CEM cells with or without mycoplasma infection were reacted with recombinant gp 120 produced in CHO cells (kindly provided by the MRC AIDS Directed Programme) for 1 h at 37°C. The cells were then incubated with a monoclonal antibody to gpl20, followed by a fluorescein conjugated rabbit antibody to mouse immunoglobulin. The cells were then analysed by flow cytometry. Mycoplasma infection of the CEM line produced a significant reduction in cell surface expression of CD4 (p < 0001); in contrast CD5 values did not change. The inhibition of CD4 expression was accompanied by a 2-log-fold reduction in the binding of gpl20 compared with that on cells lacking mycoplasma infection (figure). These findings remained consistent for 3 weeks. Infection by HIV-1(London Hospital strain X82) was compared in CEM cells with and without mycoplasma infection by means of the Coulter HIV-1p24 antigen assay. Antigen production was reduced by 50% in the presence of mycoplasma at days 6 and 12 after HIV-1infection. Our results show that this mycoplasma significantly reduced CD4 expression with consequent inhibition of gpl20 binding and HIV infection of CEM cells. Together with previously reported data this suggests that mycoplasmas can affect several stages in the life cycle of HIV-1. Departments of Medical Microbiology and Immunology, London Hospital Medical College, London E1 2AD, UK
C. O’TOOLE M. LOWDELL
1. Vasudevachari MB, Mast TC, Saizman NP. Suppression of HIV-1 reverse transcriptase activity by myocoplasma contamination of cell cultures. AIDS Res Hum Retrovirus 1990; 6: 411-16. 2. Lemaître M, Guétard D, Hénin Y, et al. Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells. Res Virol 1990; 141: 5-16. 3. Biberfeld G, Nilsson E. Mitogenicity of Mycoplasma fermentans for human
lymphocytes. Inf Immun 1978; 21: 48-54 H, Brunner H, Ruhl H. Effect of A laidlawii on murine and human lymphocyte cultures. Clin Exp Immunol 1977; 29: 176-80. 5. Chowdhury MIH, Koyanagi Y, Kobayashi S, et al. Mycoplasma and AIDS. Lancet
4. Kirchner
1990; 336: 247-48. 6. Klatzmann D, Champagne E, Chamaret S, et al. T lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 1984; 312: 767-68. 7. Dalgleish AG, Beverley PCL, Clapham PR, et al. The CD4(T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984; 312: 763-67. 8. Folley GE, Lazarus H, Faber S, et al. Continuous culture of human lymphoblasts from peripheral blood of a child with acute leukaemia. Cancer 1965; 18: 522-29. 9. Russell WC, Newman C, Williamson DH. A simple cytochemical technique for demonstration of DNA in cells infected with mycoplasmas and viruses. Nature 1975; 253: 461-62.
Cyclophosphamide versus ifosfamide in paediatric oncology SIR,-Dr Kushner and Dr Cheung (July 28, p 253) comment on the cyclophosphamide and ifosfamide in paediatric oncology. We
use of
Mycoplasma infected CEM (C).
at
day 3 (A, B) and uninfected CEM
A, stained with monoclonal antibody
to
gp120 (Du Pont) and
FITC-conjugated rabbit antibody to mouse immunoglobulms (Dako). and C, mcubated with
gp120 and
stained
as
in
(A).
B
report similar results from our group. On the basis of previous experience with an intensive cyclophosphamide regimen in the treatment of childhood brain tumours,l leading to great efficacy and to only the expected haematotoxicity, we conducted a phase-11 trial testing the efficacy of ifosfamide.2Fifty-four children received 179 courses of ifosfamide at a dose of 3 g/m2 daily over 3 h for 2 days for recurrent or refractory brain tumours. Haematotoxicity was mild, but 30% of children had neurotoxicity as has been reported for combined ifosfamide and etoposide.3 However, Miser et aP used a different dose and schedule of ifosfamide (1-8 g/m2 daily for 5 days) and neurotoxicity seemed to be less severe than in our patients. Nephrotoxicity seemed also to be a limiting factor in some of our patients. Because of this toxicity and to confirm the efficacy of cyclophosphamide we initiated a trial of cyclophosphamide with etoposide for relapsing or refractory brain tumours and for newly diagnosed brain tumours, alternating with carboplatin/etoposide: two courses of each combination were given before radiotherapy. So far, about forty courses of cyclophosphamide (15 g/m) have been given without any neurotoxicity or nephrotoxicity. Grade 3-4 neutropenia was observed in nearly all patients who had been
1068
treated by chemotherapy and craniospinal radiotherapy, without documented infection. These results encouraged us to increase the dose to 3 g/m2 over 3 days. Neutropenia was more profound but not prolonged, and neurotoxicity was not seen. The efficacy and toxicity of ifosfamide could be related to a particular mode of administration. Thus, in agreement with Dr Blackledge (June 9, p 1399), we regret the lack of comparative data for ifosfamide and cyclophosphamide. This lack has led to clinicians establishing dose schedules on the basis of published data and their own experience. The ifosfamide/cyclophosphamide and carboplatin/cisplatin dilemma should make us consider the crucial need to conduct multicentre phase-II trials testing various doses and schedules for each drug, followed by phase-III trials to ask, and especially to clarify, such questions, the answers to which will be too late for the benefit of some patients. If all new cytoxic agents were included in an international programme, we could save much time that would have been spent in reproducing known data or in testing regimens in too small (and uncontrolled) series. Department of Paediatric Oncology, P. CHASTAGNER D. SOMMELET-OLIVE, Children’s Hospital, for the French Society of Paediatric Oncology Nancy 54500, France JC, Helson L. High dose cyclophosphamide chemotherapy for recurrent CNS in children. Neurosurg 1981; 55: 749-56. J Chastagner P, Sommelet-Olive D, Kalifa C, et al. Phase II study of ifosfamide in
1. Allen
tumors
2.
recurrent childhood brain tumors. Pediatr Neurosci 1990; 15: 147. 3. Miser J, Krailo M, Smithson W, et al. Treatment of children with recurrent brain tumors with ifosfamide, etoposide and mesna. Proc Am Soc Clin Oncol 1989; 8: 84.
5 min, when the number of fetal similar to that normally observed in fetuses of that age. During the period of increased activity the fetus changed position frequently. The effects probably represent a direct effect of maternal psychological ’shock’; we have previously noted that changes in maternal position do not influence fetal movements. Increased fetal movement may be mediated by release of adrenaline or cortisol into the bloodstream. These observations indicate that brief periods of increased maternal emotionality, which may be considered everyday occurrences, can influence the behaviour of the fetus. Studies of maternal emotionality and reproductive outcome should not be restricted to severe or long-term heightened emotionality but should also take into account milder, more transient episodes.
gradually subsided after movements was
School of Psychology, Queen’s University of Belfast, Belfast BT7 1NN, UK
PETER G. HEPPER
Royal Maternity Hospital, Belfast
SARA SHAHIDULLAH
1.
Hepper PG. Foetal learning: implications for psychiatry? BrJ Psychiatry 1989; 155:
289-93. 2. Carlson B, LaBarba C. Maternal emotionality during pregnancy and reproductive outcome: a review of the literature J Behav Develop 1979; 2: 342-76. 3. Ferreira AJ. Emotional factors in prenatal environment. J Nerv Ment Dis 1965; 141: 108-18. 4. Sontag LW. The significance of fetal environmental differences. Am JObstet Gynecol
1941; 42: 96-103.
Herbs and Fetal response to maternal shock SIR,-Early writers such as Hippocrates proposed that maternal emotions influence pregnancy, and since then there has been much interest in the effect of maternal emotional state upon the development of the fetus.2,3 Research has concentrated upon the effects of chronic long-term or severely heightened emotionality’ (eg, after the death of the husband4), and the effects of milder short-lasting changes, such as those due to a shock or surprise, have not been examined. A healthy 27-year-old woman with an uncomplicated pregnancy missed her footing whilst climbing onto a couch for a scan and fell backwards, ending up on the floor. She was not hurt but was shocked and embarrassed rather than distressed. A minute later and fully recovered (her heart rate was 69/min) she remounted the couch and was scanned (’ATL Ultramark 4plus’ with a 3-5 MHz scan head). Her fetus, age about 16 weeks on scan measurements, was observed for 10 min. Fetal arm and leg movements were recorded. A period of fetal hyperactivity (figure)
.1.uu
BUUI)
Arm and leg movements exhibited by fetus of shocked mother and those exhibited by fetus of an unshocked mother.
hepatitis
SIR,-Dr Davies and colleagues (July 21, p 177) report hepatitis, probably toxic, from herbal therapy of eczema in a young girl. I have similar cases. I am the manager of a health control laboratory. From blood tests and physical examination we give advice about diet and lifestyle. For example, high blood lipids and the common hyperinsulin syndrome can be controlled with the help of data from the laboratory and changes in habit. An unexpected finding was the high frequency of liver abnormalities. Some abnormalities were the result of alcohol abuse, prediabetes, drugs, solvents, carcinomas, or other known conditions; however, they seemed to be most common in patients who took herbal preparations. 395 patients (the first 5 to present each day for about 80 days) were thoroughly investigated. In 160 patients (mean age 50 years) who took no drugs or alcohol and without known disease the mean serum gamma-glutamyltransferase (S-GT) was 0-19 cat/1. In a similar group of 53 people (mean age 52) who took herbal preparations, selenium, or homoeopathic remedies, the mean S-GT was 0-91 pcat/1; in 15 alcoholics (mean age 44) the mean S-GT was 1-35 pcat/1. However, the 4 patients with the highest S-GT values were all in the herbal preparation group, and they had hepatitis-like results by other liver tests. All patients in the herb-taking group were offered a free examination 6 weeks after initial testing. 12 agreed to stop taking herbal preparations and returned for follow-up. All but 1 had more normal values than before. This patient, a 40-year-old woman, had liver cirrhosis. 167 of the 395 patients took drugs or alcohol, were exposed to solvents, had known disease, or had a combination of these factors. Those in this group who took herbal preparations again had increased S-GT concentrations. Of about 15 patients the laboratory investigates every day, 1 or more regularly have liver abnormalities that disappear if they stop taking herbal preparations. Usually several remedies are taken at the same time. In Sweden, as elsewhere, physicians must report side-effects of drugs, but there is no such rule for herbal preparations. People have a strong belief in herbal preparations, and most physicians do not ask if they are taken. Perhaps we should not be surprised at the toxic effects of herbs. Many plants are protected by toxins which discourage consumption by animals. Herbal preparations may come from plants that are not eaten by other mammals. seen
Health Care Home, 53397 Gotene, Sweden
CARL CARLSSON
We agree with Goesch and colleagues about the risk of transfer of P carinii between immunosuppressed patients. Moreover, there is laboratory evidence to support such transfer.4 Despite the lack of official guidelines5 patients with active PCP should be isolated. TH. BENSOUSAN B. GARO S. ISLAM B. BOURBIGOT J. CLEDES M. GALE
Departments of Intensive Care and Infectious Diseases and Nephrology and Renal Transplantation, University Hospital of Brest, 29285 Brest, France
1.Gajdusek
DC.
Pneumocystis carinii: aetiologic agent with interstitial plasma cell
pneumonia of premature and young infants. Pediatrics 1957; 19: 543-65. 2. Hardy
AP, Wajszczuk CP, Suffredini AF, Hakala TR, Monto HO. Pneumocystis m renal transplant recipients treated with cyclosporine and
carinii pneumonia
steroids. J Infect Dis 1984; 149: 143-47. 3. Ferec C, Bourbigot B, Verlingue C, et al. Circadian variation of lymphocyte subsets after renal transplantation. Transplant Proc 1986; 18: 1308-10. 4. Hughes WT. Natural mode of acquisition for de novo infection with Pneumocystis carinii. J Infect Dis 1982; 145: 842-48. 5. Walzer PD. Pneumocystis carinii: principles and practice of infectious diseases. New York: Churchill Livingstone, 1990: 2103-10.
Infection of human T cells with mycoplasma, inhibition of CD4 expression and HIV-1 gp120 glycoprotein binding, and
infectivity SIR,-Myocoplasma species have been shown to influence HIV-1I growth in human T-cell lines. Introduction of mycoplasma to cultures depresses HIV-1 replication as measured by reverse transcriptase (RT) activity, and treatment of HIV-1 infected T cells with antimycoplasma tetracyclines causes an increase in RT activity.1,2 Mycoplasmas are known to be mitogenic for human T and B cells,3.4 and killed mycoplasma can stimulate HIV-1 p24 antigen production in T-cell lines.s We have shown that a glucose-fermenting mycoplasma, isolated from lymphoid cells of an HIV-1 infected patient with AIDS-related complex, affects the HIV-1 envelope receptor CD46’ expression by T cells. Infection of the human T-cell line CEM8 with this organism led to a specific reduction in the expression of CD4, accompanied by a decrease in binding of the HIV-1 envelope protein gpl20. CEM cells were infected with mycoplasma and observed for 3 weeks during which time mycoplasma infection was monitored by electronmicroscopy and by DNA staining.9 Cell surface expression of CD4 and gp 120 binding were first examined 3 days after mycoplasma infection. Cells were reacted with monoclonal antibodies to CD4 (Leu 3a/3b) or CD5 (Leu 1), a cell surface molecule on CEM unrelated to HIV binding, and compared with uninfected CEM. The expression of each surface antigen was tested in quadruplicate and then analysed in triplicate by flow cytometry (’Facscan’, Becton Dickinson). CD4
and CD5were measured as the median channel of the fluorescence histograms. Differences between these values were assessed with Student’s t-test. To measure gpl20 binding, CEM cells with or without mycoplasma infection were reacted with recombinant gp 120 produced in CHO cells (kindly provided by the MRC AIDS Directed Programme) for 1 h at 37°C. The cells were then incubated with a monoclonal antibody to gpl20, followed by a fluorescein conjugated rabbit antibody to mouse immunoglobulin. The cells were then analysed by flow cytometry. Mycoplasma infection of the CEM line produced a significant reduction in cell surface expression of CD4 (p < 0001); in contrast CD5 values did not change. The inhibition of CD4 expression was accompanied by a 2-log-fold reduction in the binding of gpl20 compared with that on cells lacking mycoplasma infection (figure). These findings remained consistent for 3 weeks. Infection by HIV-1(London Hospital strain X82) was compared in CEM cells with and without mycoplasma infection by means of the Coulter HIV-1p24 antigen assay. Antigen production was reduced by 50% in the presence of mycoplasma at days 6 and 12 after HIV-1infection. Our results show that this mycoplasma significantly reduced CD4 expression with consequent inhibition of gpl20 binding and HIV infection of CEM cells. Together with previously reported data this suggests that mycoplasmas can affect several stages in the life cycle of HIV-1. Departments of Medical Microbiology and Immunology, London Hospital Medical College, London E1 2AD, UK
C. O’TOOLE M. LOWDELL
1. Vasudevachari MB, Mast TC, Saizman NP. Suppression of HIV-1 reverse transcriptase activity by myocoplasma contamination of cell cultures. AIDS Res Hum Retrovirus 1990; 6: 411-16. 2. Lemaître M, Guétard D, Hénin Y, et al. Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells. Res Virol 1990; 141: 5-16. 3. Biberfeld G, Nilsson E. Mitogenicity of Mycoplasma fermentans for human
lymphocytes. Inf Immun 1978; 21: 48-54 H, Brunner H, Ruhl H. Effect of A laidlawii on murine and human lymphocyte cultures. Clin Exp Immunol 1977; 29: 176-80. 5. Chowdhury MIH, Koyanagi Y, Kobayashi S, et al. Mycoplasma and AIDS. Lancet
4. Kirchner
1990; 336: 247-48. 6. Klatzmann D, Champagne E, Chamaret S, et al. T lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 1984; 312: 767-68. 7. Dalgleish AG, Beverley PCL, Clapham PR, et al. The CD4(T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984; 312: 763-67. 8. Folley GE, Lazarus H, Faber S, et al. Continuous culture of human lymphoblasts from peripheral blood of a child with acute leukaemia. Cancer 1965; 18: 522-29. 9. Russell WC, Newman C, Williamson DH. A simple cytochemical technique for demonstration of DNA in cells infected with mycoplasmas and viruses. Nature 1975; 253: 461-62.
Cyclophosphamide versus ifosfamide in paediatric oncology SIR,-Dr Kushner and Dr Cheung (July 28, p 253) comment on the cyclophosphamide and ifosfamide in paediatric oncology. We
use of
Mycoplasma infected CEM (C).
at
day 3 (A, B) and uninfected CEM
A, stained with monoclonal antibody
to
gp120 (Du Pont) and
FITC-conjugated rabbit antibody to mouse immunoglobulms (Dako). and C, mcubated with
gp120 and
stained
as
in
(A).
B
report similar results from our group. On the basis of previous experience with an intensive cyclophosphamide regimen in the treatment of childhood brain tumours,l leading to great efficacy and to only the expected haematotoxicity, we conducted a phase-11 trial testing the efficacy of ifosfamide.2Fifty-four children received 179 courses of ifosfamide at a dose of 3 g/m2 daily over 3 h for 2 days for recurrent or refractory brain tumours. Haematotoxicity was mild, but 30% of children had neurotoxicity as has been reported for combined ifosfamide and etoposide.3 However, Miser et aP used a different dose and schedule of ifosfamide (1-8 g/m2 daily for 5 days) and neurotoxicity seemed to be less severe than in our patients. Nephrotoxicity seemed also to be a limiting factor in some of our patients. Because of this toxicity and to confirm the efficacy of cyclophosphamide we initiated a trial of cyclophosphamide with etoposide for relapsing or refractory brain tumours and for newly diagnosed brain tumours, alternating with carboplatin/etoposide: two courses of each combination were given before radiotherapy. So far, about forty courses of cyclophosphamide (15 g/m) have been given without any neurotoxicity or nephrotoxicity. Grade 3-4 neutropenia was observed in nearly all patients who had been
1068
treated by chemotherapy and craniospinal radiotherapy, without documented infection. These results encouraged us to increase the dose to 3 g/m2 over 3 days. Neutropenia was more profound but not prolonged, and neurotoxicity was not seen. The efficacy and toxicity of ifosfamide could be related to a particular mode of administration. Thus, in agreement with Dr Blackledge (June 9, p 1399), we regret the lack of comparative data for ifosfamide and cyclophosphamide. This lack has led to clinicians establishing dose schedules on the basis of published data and their own experience. The ifosfamide/cyclophosphamide and carboplatin/cisplatin dilemma should make us consider the crucial need to conduct multicentre phase-II trials testing various doses and schedules for each drug, followed by phase-III trials to ask, and especially to clarify, such questions, the answers to which will be too late for the benefit of some patients. If all new cytoxic agents were included in an international programme, we could save much time that would have been spent in reproducing known data or in testing regimens in too small (and uncontrolled) series. Department of Paediatric Oncology, P. CHASTAGNER D. SOMMELET-OLIVE, Children’s Hospital, for the French Society of Paediatric Oncology Nancy 54500, France JC, Helson L. High dose cyclophosphamide chemotherapy for recurrent CNS in children. Neurosurg 1981; 55: 749-56. J Chastagner P, Sommelet-Olive D, Kalifa C, et al. Phase II study of ifosfamide in
1. Allen
tumors
2.
recurrent childhood brain tumors. Pediatr Neurosci 1990; 15: 147. 3. Miser J, Krailo M, Smithson W, et al. Treatment of children with recurrent brain tumors with ifosfamide, etoposide and mesna. Proc Am Soc Clin Oncol 1989; 8: 84.
5 min, when the number of fetal similar to that normally observed in fetuses of that age. During the period of increased activity the fetus changed position frequently. The effects probably represent a direct effect of maternal psychological ’shock’; we have previously noted that changes in maternal position do not influence fetal movements. Increased fetal movement may be mediated by release of adrenaline or cortisol into the bloodstream. These observations indicate that brief periods of increased maternal emotionality, which may be considered everyday occurrences, can influence the behaviour of the fetus. Studies of maternal emotionality and reproductive outcome should not be restricted to severe or long-term heightened emotionality but should also take into account milder, more transient episodes.
gradually subsided after movements was
School of Psychology, Queen’s University of Belfast, Belfast BT7 1NN, UK
PETER G. HEPPER
Royal Maternity Hospital, Belfast
SARA SHAHIDULLAH
1.
Hepper PG. Foetal learning: implications for psychiatry? BrJ Psychiatry 1989; 155:
289-93. 2. Carlson B, LaBarba C. Maternal emotionality during pregnancy and reproductive outcome: a review of the literature J Behav Develop 1979; 2: 342-76. 3. Ferreira AJ. Emotional factors in prenatal environment. J Nerv Ment Dis 1965; 141: 108-18. 4. Sontag LW. The significance of fetal environmental differences. Am JObstet Gynecol
1941; 42: 96-103.
Herbs and Fetal response to maternal shock SIR,-Early writers such as Hippocrates proposed that maternal emotions influence pregnancy, and since then there has been much interest in the effect of maternal emotional state upon the development of the fetus.2,3 Research has concentrated upon the effects of chronic long-term or severely heightened emotionality’ (eg, after the death of the husband4), and the effects of milder short-lasting changes, such as those due to a shock or surprise, have not been examined. A healthy 27-year-old woman with an uncomplicated pregnancy missed her footing whilst climbing onto a couch for a scan and fell backwards, ending up on the floor. She was not hurt but was shocked and embarrassed rather than distressed. A minute later and fully recovered (her heart rate was 69/min) she remounted the couch and was scanned (’ATL Ultramark 4plus’ with a 3-5 MHz scan head). Her fetus, age about 16 weeks on scan measurements, was observed for 10 min. Fetal arm and leg movements were recorded. A period of fetal hyperactivity (figure)
.1.uu
BUUI)
Arm and leg movements exhibited by fetus of shocked mother and those exhibited by fetus of an unshocked mother.
hepatitis
SIR,-Dr Davies and colleagues (July 21, p 177) report hepatitis, probably toxic, from herbal therapy of eczema in a young girl. I have similar cases. I am the manager of a health control laboratory. From blood tests and physical examination we give advice about diet and lifestyle. For example, high blood lipids and the common hyperinsulin syndrome can be controlled with the help of data from the laboratory and changes in habit. An unexpected finding was the high frequency of liver abnormalities. Some abnormalities were the result of alcohol abuse, prediabetes, drugs, solvents, carcinomas, or other known conditions; however, they seemed to be most common in patients who took herbal preparations. 395 patients (the first 5 to present each day for about 80 days) were thoroughly investigated. In 160 patients (mean age 50 years) who took no drugs or alcohol and without known disease the mean serum gamma-glutamyltransferase (S-GT) was 0-19 cat/1. In a similar group of 53 people (mean age 52) who took herbal preparations, selenium, or homoeopathic remedies, the mean S-GT was 0-91 pcat/1; in 15 alcoholics (mean age 44) the mean S-GT was 1-35 pcat/1. However, the 4 patients with the highest S-GT values were all in the herbal preparation group, and they had hepatitis-like results by other liver tests. All patients in the herb-taking group were offered a free examination 6 weeks after initial testing. 12 agreed to stop taking herbal preparations and returned for follow-up. All but 1 had more normal values than before. This patient, a 40-year-old woman, had liver cirrhosis. 167 of the 395 patients took drugs or alcohol, were exposed to solvents, had known disease, or had a combination of these factors. Those in this group who took herbal preparations again had increased S-GT concentrations. Of about 15 patients the laboratory investigates every day, 1 or more regularly have liver abnormalities that disappear if they stop taking herbal preparations. Usually several remedies are taken at the same time. In Sweden, as elsewhere, physicians must report side-effects of drugs, but there is no such rule for herbal preparations. People have a strong belief in herbal preparations, and most physicians do not ask if they are taken. Perhaps we should not be surprised at the toxic effects of herbs. Many plants are protected by toxins which discourage consumption by animals. Herbal preparations may come from plants that are not eaten by other mammals. seen
Health Care Home, 53397 Gotene, Sweden
CARL CARLSSON
