63
committee could issue twice yearly guidelines based on scientific evidence for chemoprophylaxis and treatment of malaria. Hopefully, that would avoid the need for recommendations such as that of Bames et al, which only fuel controversy and confusion. Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK
A. ZUMLA
Breckenridge A. Risks and benefits of prophylactic antimalarial drugs
Br Med J 1989, 299: 1057-58. 2 Zumla A, Laurenson I. Malaria prophylaxis-a persisting dilemma J Antimicrob Chemother 1989; 23: 809-10. 3 Cook GC. Plasmodium falciparum infections: problems in prophylaxis and treatment in 1986. QJ Med 1986; 236: 1091-115. 4. Editorial. Malaria mosquito control and primary health care. Lancet 1988; i: 511-12. 5. Henderson A, Rixom JA. Personal antimosquito measures plus proguanil for malaria prophylaxis in Southern Malaysia. Trans R Soc Trop Med Hyg 1986; 80: 981-82 1
SIR,-Dr Barnes and colleagues report a case of severe malaria to Kenya, despite prophylaxis with chloroquine and proguanil. We have lately treated a patient with cerebral malaria, which was eventually fatal. The illness developed while he was still taking prophylaxis with chloroquine and proguanil. A 58-year-old Ghanaian man who had lived in the UK for 21 years returned to Ghana for a 3-week holiday, visiting Accra and rural areas near the Volta dam. He took chloroquine 300 mg every week and proguanil 200 mg daily. On the day after return to the UK after travel
he became unwell and vomited. He was admitted but rapidly became unconscious. He had a temperature of 39°C, was oliguric, and unrousable without neck stiffness, papilloedema, or focal neurological signs. There were signs of left basal consolidation. A blood film showed 28% parasitaemia with Plasmodium falciparum. He also had diabetic ketoacidosis (blood glucose 33 mmol/1, arterial pH 702, P02 17kPa, PCO, 24 kPa, bicarbonate 4 mmol/1), but no history of diabetes. The patient’s wife confirmed that he had taken chloroquine and proguanil before travelling and since his return to the UK. A count of the remaining tablets revealed that he had taken all the prescribed chloroquine and 65% of the
proguanil. The patient was intubated and mechanically ventilated, treated with intravenous quinine 20 mg/kg as a loading dose followed by 10 mg/kg 8-12 hourly, and intravenous antibiotics. Exchange transfusion with ten units of blood lowered the parasitaemia to 2% within 12 h, and trophozoites were cleared from the blood within 5 days. Nevertheless, left hemiparesis, acute renal failure requiring treatment with haemofiltration, and gangrene of the scrotum requiring surgical debridement developed, and he died 8 days after admission. Necropsy revealed severe bilateral bronchopneumonia, right anterior cerebral and left occipital infarcts, and coronary atherosclerosis. This case, like that of Bames et al, demonstrates that prophylaxis with chloroquine and proguanil does not give absolute protection against severe or fatal malaria. Pfalciparum in west Africa may be highly resistant to chloroquine, and physicians need to be increasingly aware of the possibility of malaria even in travellers who have complied fully with prophylaxis. London NW1 0PE, UK
DUNCAN CHURCHILL ROBERT DAVIDSON
Cross Hospital, London W6
KIERAN O’FLYNN WOLFGANG KOX
Hospital for Tropical Diseases,. Charing
SiR,—The standard French prophylactic regimen for travellers
visiting
central and
proguanil 200
west
Africa is
chloroquine
100 mg
plus
mefloquine 250 mg per week. Since January, 1991, 80 travellers with falciparum malaria returning from central and west Africa have been treated at our hospital. 47 had not mg
daily
or
taken any chemoprophylaxis. 20 terminated prophylaxis less than 2 weeks after returning to France or took substandard doses of chloroquine alone (n = 14), chloroquine and proguanil (n = 2), mefloquine Cn = 1), or other antimalarial drugs (n = 3). Malaria parasites obtained from 48 patients who did not take any drug or were non-compliant with chloroquine intake and who had a
parasitaemia of at least 0-07% were tested for in-vitro chloroquine susceptibility. 14 of 28 successful tests showed that the isolates were susceptible to chloroquine, indicating that had these patients been fully compliant with chloroquine and proguanil prophylaxis, at least half of them would most probably have had eliminated the parasites completely. 13 patients had malaria despite full compliance with prophylaxis (chloroquine alone 7, chloroquine plus proguanil 5, mefloquine 1). The parasites isolated from 3 patients on 100 mg chloroquine per day were indeed resistant in vitro to chloroquine, whereas the parasites from a patient who took 300 mg of chloroquine weekly were susceptible in vitro to the drug. 4 isolates from failures of chloroquine and proguanil prophylaxis were resistant in vitro to chloroquine, 1 of them (the only one tested) being also resistant to cycloguanil, the biologically active metabolite of proguanil. Mefloquine resistance in a patient who attained a therapeutically effective plasma concentration was confirmed in vitro (mefloquine median inhibitory concentration 31 nmol/1). In our experience most malaria-infected returning travellers have either not taken prophylaxis at all or have done so at insufficient doses. A better education of travellers to tropical Africa is needed.
Departments of Parasitology and Infectious Diseases and Tropical Medicine, Hôpital Bichat-Claude Bernard, 75018 Paris, France
LEONARDO K. BASCO JACQUES LE BRAS GUY CHARMOT JEAN-LOUIS VILDE FRANCOIS VACHON JEAN-PIERRE COULAUD
SIR,-Dr Barnes and colleagues’ experience has been interpreted prophylaxis failure, for which they promote mefloquine as a superior chemoprophylaxis regiment In a prospective study of 309 patients with falciparum malaria presenting to this hospital, detailed information on chemoprophylaxis and compliance revealed that
as
42% of patients took no chemoprophylaxis, 38% used it irregularly, and half of the remaining 20% compliant users took the recommended chloroquine and proguanil. The study was also designed to correlate self-reported drug compliance with plasma drug concentrations of chloroquine and there were significant
discrepancies. In 16 patients reporting good compliance (no missed doses), plasma levels commensurate with this drug history were found in only 5.2 The data suggest that most cases of malaria seen here cannot be attributed solely to infection with drug-resistant falciparum malaria and that failure of compliance with prophylaxis is more probably to blame. It seems incongruous to alter the current regimen to mefloquine when there is no objective evidence of failure of chloroquine and proguanil. We emphasise the need for personal protection measures together with full chemoprophylaxis, and we inform travellers of the symptoms of malaria to try to prevent delay in diagnosis on their return to the UK. Travel Clinic, Hospital for Tropical Diseases, London NW1 OPE, UK
R. H. BEHRENS
1. Ross Institute.
Prophylaxis against malaria for travellers from the United Kingdom. Br Med J 1989; 299: 1087-89. 2. Behrens RH, Pryce D, Taylor RB, Low ST. Comparison of reported compliance to plasma levels of chemoprophylactic drugs in patients with malaria. In: Lobel HO, ed. Proceedings of 2nd International Conference on Travel Medicine. Atlanta, Georgia. Centers for Disease Control (m press).
Twins with different fathers SIR,-Most mammals discharge several ova during ovulation, resulting in multiple births. In women a single ovum discharge is the norm since their ovaries generally alternate egg production. However, there are exceptions, the result being dizygotic (DZ) twins for example, and if a woman has intercourse with different men during polyovulation twins with different fathers would be possible. Archerl in 1810 observed radically different twins (one white, the other mulatto) with two different fathers. Geyer’ in 1940 identified DZ twins with different fathers by red cell antigen typing, these findings being endorsed by HLA typing.3
64
percentage of patients delivering withm 8 h of induction was 36 % in group 1 and 73% in group 2 and the misoprostol doses required averaged 162 pg and 188 ng, respectively. More than half the
patients responded
Cytogenetic markers on chromosome 18 in alleged father (A), mother (B), son (D), and daughter (E). Alul-Giemsa-resistant chromatin present on both chromosomes 188 alleged father is shared by son but not by daughter. Size of Y in alleged father is apparently present in son Legal father (C) refused to in
participate We report a case of DZ twins of different sex, where the alleged father refused to take responsibility for the children, claiming they belonged to the legal father. The legal father refused to take part in a paternity determination. Informative cytogenetic markers were seen in the alleged father and the son. The most remarkable observation in the alleged father was the presence of restriction endonuclease AluI resistant chromatin’ on both chromosomes 18. The son had one positive chromosome 18 whereas both of the daughter’s chromosomes 18 were negative (figure). The alleged father was typed ss and the daughter was SS, suggesting that he could not be the biological father of the daughter, but the unusual heteromorphic markers found in the alleged father were shared by the son. The size of the Y chromosome is a variable anthropological trait in man.’ The alleged father and the son both have the same size Y chromosome. Once the alleged father was informed of these results, he immediately refused DNA fingerprinting. It seemed that the mother had had intercourse with two different men around the time of ovulation, and she admitted to this during
counselling. Department of Laboratories, Long Island College HospitalSUNY Health Science Center, Brooklyn, NY 11201, USA
1. Archer J. Facts illustrating a disease peculiar to the female children of negro slaves. Med Reposit 1810, 1: 319-23 2 Geyer E. Ein Zwillings parchen mit Zwei Vatem (Nachgewiesence Uberschwangerung beim Menschen). Arch Rassenbiol 1940, 34: 226 3. Terasaki PI, Gjertson D, Bemoco D, et al Twins with two different fathers identified by HLA. N Engl JMed 1978; 299: 590-92. 4. Verma RS, Babu A. Human chromosomes manual of basic technique New York: Pergamon, 1989: 93-95. 5. Verma RS, Pandey RP. Nonrandom distribution of various sizes of human Y chromosomes in different ethnic group Ann Hum Biol 1987; 14: 271-76
Misoprostol to induce labour SiR,—We have done two studies’2 that corroborate the efficacy of vaginal misoprostol in inducing uterine contractions during the third trimester of pregnancy-a dose-finding study and a comparative trial of misoprostol and oxytocin. In the dose-ranging study (published in a journal covered by Current Contents and summarised very briefly here) patients were at gestational age 28-36 weeks (n = 11) or more than 36 weeks (n = 45), and induction of labour was medically indicated. An initial dose of 50 ug, in the posterior vaginal fornix, was followed by increasing doses of 50 Ilg every 2 h until satisfactory uterine activity was achieved. The maximum permitted was 600 Ilg. Induction was considered successful if the patient delivered within 8 h. 36% and 69% of women in groups 1 and 2, respectively, were nulliparous. The
single 50
pg dose. 3 women
J A Fernández Hospital, University of Buenos Aires,
reported
MIGUEL MARGULIES GERMAN CAMPOS PÉREZ LILIANA S. VOTO
1119-Beunos Aires, Argentina; and School of Medicine, Universidad Austral de Chile
1. Margulies M, Voto LS, Catuzzi P, Uranga Imaz F. Inducción del trabajo de parto con un análogo de la PgE1. Un estudio abierto, no comparativo, de hallazgo de dosis. Prensa Méd Arg 1991; 78: 9-13 2. Campos Pérez GA, Margulies M, Ortega I, Voto LS. Induction of labor with Misoprostol, a PgE1 analog: a comparative study. Proceedings of 2nd European Congress on Prostaglandins in Reproduction (The Hague, Netherlands, April 30-May 3, 1991).
Oral R. S. VERMA S. LUKE P. DHAWAN
to a
diarrhoea and hot flushes but no adverse effects on the fetus or baby were observed. The second study was a randomised, controlled trial in 64 patients with a single fetus and intact membranes and in whom induction was necessary for medical or obstetric indications.2 In 33 patients a tablet containing 50 ng misoprostol was placed in the posterior fornix ; the other 31 were given intravenous oxytocin. Successful induction was defmed as vaginal delivery within 24 h from the moment when three contractions in 10 min were detected. Gestational age and Bishop score at entry were not significantly different in the misoprostol and oxytocin groups. In the misoprostol group, induction was successful in 26 (79%) patients; 1 patient was delivered by caesarean section because of fetal distress. In the oxytocin group, induction was successful in 19 (62 %), and 8 women had caesarean section, 5 of them for failure of labour to progress and 3 because of fetal distress. Induction-to-delivery interval was 407 (SD 265) min in the misoprostol group and 577 (605) in the oxytocin group (p = 0-2). No differences were found in birthweight or Apgar scores. Side-effects were not observed, but polysystole (more than 5 contractions in 10 min) was more frequent in the misoprostol group (17%) than in the oxytocin group (12 %); however, no fetal distress was associated with this condition in either group. Our findings suggest that misoprostol is effective in the induction of labour in the third trimester of gestation, with few side-effects on the mother and no apparent adverse effects on the fetus or newborn baby. In our population efficacy of misoprostol was comparable with that of oxytocin.
immunosuppression for multiple sclerosis
SIR,-With due respect for the efforts of the initial investigators and Professor Yudkin and colleagues’ (Oct 26, p 1051) overview indicating a marginal benefit of azathioprine for multiple sclerosis, I suggest that the treatment programmes were not adequate. First, most patients were treated with 2-25 mg/kg daily; 3 mg/kg daily was used in only one of the groups evaluated at 2 years (and in none of those evaluated at 3 years), and that group consisted of only 10% (21/206) of the patients treated for 2 years. Second, only two of the trial groups attempted to use a biological indicator of azathioprine effect, and they used the wrong oneleucocyte count, presumably for efficacy and/or safety. The leucocyte count is an archaic value-that should be proscribedconsisting mainly of two totally different cell populations, which during immunosuppression treatment can have opposite implications. I customise long-term immunosuppression for each patient. 1-1For safety I do not allow the neutrophils (granulocytes) to drop below 2000/1; for efficacy I try to reduce the total lymphocyte population to below 700/1 ( < 400 is acceptable), if necessary by carefully raising the dose with monitoring of the neutrophil count. The lymphocytes themselves are a mixed population consisting of only some so-called bad ones, but this lower-than-700 goal and imprecise rationale seem to have correlated with clinical benefit in the various neuromuscular diseases that have been treated (eg, polymyositis/dermatomyositis, myasthenia gravis, and chronic dysimmune neuropathies). Third, although the preferred drug for long-term treatment of dysimmune neuromuscular diseases is controversial, since about
committee could issue twice yearly guidelines based on scientific evidence for chemoprophylaxis and treatment of malaria. Hopefully, that would avoid the need for recommendations such as that of Bames et al, which only fuel controversy and confusion. Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK
A. ZUMLA
Breckenridge A. Risks and benefits of prophylactic antimalarial drugs
Br Med J 1989, 299: 1057-58. 2 Zumla A, Laurenson I. Malaria prophylaxis-a persisting dilemma J Antimicrob Chemother 1989; 23: 809-10. 3 Cook GC. Plasmodium falciparum infections: problems in prophylaxis and treatment in 1986. QJ Med 1986; 236: 1091-115. 4. Editorial. Malaria mosquito control and primary health care. Lancet 1988; i: 511-12. 5. Henderson A, Rixom JA. Personal antimosquito measures plus proguanil for malaria prophylaxis in Southern Malaysia. Trans R Soc Trop Med Hyg 1986; 80: 981-82 1
SIR,-Dr Barnes and colleagues report a case of severe malaria to Kenya, despite prophylaxis with chloroquine and proguanil. We have lately treated a patient with cerebral malaria, which was eventually fatal. The illness developed while he was still taking prophylaxis with chloroquine and proguanil. A 58-year-old Ghanaian man who had lived in the UK for 21 years returned to Ghana for a 3-week holiday, visiting Accra and rural areas near the Volta dam. He took chloroquine 300 mg every week and proguanil 200 mg daily. On the day after return to the UK after travel
he became unwell and vomited. He was admitted but rapidly became unconscious. He had a temperature of 39°C, was oliguric, and unrousable without neck stiffness, papilloedema, or focal neurological signs. There were signs of left basal consolidation. A blood film showed 28% parasitaemia with Plasmodium falciparum. He also had diabetic ketoacidosis (blood glucose 33 mmol/1, arterial pH 702, P02 17kPa, PCO, 24 kPa, bicarbonate 4 mmol/1), but no history of diabetes. The patient’s wife confirmed that he had taken chloroquine and proguanil before travelling and since his return to the UK. A count of the remaining tablets revealed that he had taken all the prescribed chloroquine and 65% of the
proguanil. The patient was intubated and mechanically ventilated, treated with intravenous quinine 20 mg/kg as a loading dose followed by 10 mg/kg 8-12 hourly, and intravenous antibiotics. Exchange transfusion with ten units of blood lowered the parasitaemia to 2% within 12 h, and trophozoites were cleared from the blood within 5 days. Nevertheless, left hemiparesis, acute renal failure requiring treatment with haemofiltration, and gangrene of the scrotum requiring surgical debridement developed, and he died 8 days after admission. Necropsy revealed severe bilateral bronchopneumonia, right anterior cerebral and left occipital infarcts, and coronary atherosclerosis. This case, like that of Bames et al, demonstrates that prophylaxis with chloroquine and proguanil does not give absolute protection against severe or fatal malaria. Pfalciparum in west Africa may be highly resistant to chloroquine, and physicians need to be increasingly aware of the possibility of malaria even in travellers who have complied fully with prophylaxis. London NW1 0PE, UK
DUNCAN CHURCHILL ROBERT DAVIDSON
Cross Hospital, London W6
KIERAN O’FLYNN WOLFGANG KOX
Hospital for Tropical Diseases,. Charing
SiR,—The standard French prophylactic regimen for travellers
visiting
central and
proguanil 200
west
Africa is
chloroquine
100 mg
plus
mefloquine 250 mg per week. Since January, 1991, 80 travellers with falciparum malaria returning from central and west Africa have been treated at our hospital. 47 had not mg
daily
or
taken any chemoprophylaxis. 20 terminated prophylaxis less than 2 weeks after returning to France or took substandard doses of chloroquine alone (n = 14), chloroquine and proguanil (n = 2), mefloquine Cn = 1), or other antimalarial drugs (n = 3). Malaria parasites obtained from 48 patients who did not take any drug or were non-compliant with chloroquine intake and who had a
parasitaemia of at least 0-07% were tested for in-vitro chloroquine susceptibility. 14 of 28 successful tests showed that the isolates were susceptible to chloroquine, indicating that had these patients been fully compliant with chloroquine and proguanil prophylaxis, at least half of them would most probably have had eliminated the parasites completely. 13 patients had malaria despite full compliance with prophylaxis (chloroquine alone 7, chloroquine plus proguanil 5, mefloquine 1). The parasites isolated from 3 patients on 100 mg chloroquine per day were indeed resistant in vitro to chloroquine, whereas the parasites from a patient who took 300 mg of chloroquine weekly were susceptible in vitro to the drug. 4 isolates from failures of chloroquine and proguanil prophylaxis were resistant in vitro to chloroquine, 1 of them (the only one tested) being also resistant to cycloguanil, the biologically active metabolite of proguanil. Mefloquine resistance in a patient who attained a therapeutically effective plasma concentration was confirmed in vitro (mefloquine median inhibitory concentration 31 nmol/1). In our experience most malaria-infected returning travellers have either not taken prophylaxis at all or have done so at insufficient doses. A better education of travellers to tropical Africa is needed.
Departments of Parasitology and Infectious Diseases and Tropical Medicine, Hôpital Bichat-Claude Bernard, 75018 Paris, France
LEONARDO K. BASCO JACQUES LE BRAS GUY CHARMOT JEAN-LOUIS VILDE FRANCOIS VACHON JEAN-PIERRE COULAUD
SIR,-Dr Barnes and colleagues’ experience has been interpreted prophylaxis failure, for which they promote mefloquine as a superior chemoprophylaxis regiment In a prospective study of 309 patients with falciparum malaria presenting to this hospital, detailed information on chemoprophylaxis and compliance revealed that
as
42% of patients took no chemoprophylaxis, 38% used it irregularly, and half of the remaining 20% compliant users took the recommended chloroquine and proguanil. The study was also designed to correlate self-reported drug compliance with plasma drug concentrations of chloroquine and there were significant
discrepancies. In 16 patients reporting good compliance (no missed doses), plasma levels commensurate with this drug history were found in only 5.2 The data suggest that most cases of malaria seen here cannot be attributed solely to infection with drug-resistant falciparum malaria and that failure of compliance with prophylaxis is more probably to blame. It seems incongruous to alter the current regimen to mefloquine when there is no objective evidence of failure of chloroquine and proguanil. We emphasise the need for personal protection measures together with full chemoprophylaxis, and we inform travellers of the symptoms of malaria to try to prevent delay in diagnosis on their return to the UK. Travel Clinic, Hospital for Tropical Diseases, London NW1 OPE, UK
R. H. BEHRENS
1. Ross Institute.
Prophylaxis against malaria for travellers from the United Kingdom. Br Med J 1989; 299: 1087-89. 2. Behrens RH, Pryce D, Taylor RB, Low ST. Comparison of reported compliance to plasma levels of chemoprophylactic drugs in patients with malaria. In: Lobel HO, ed. Proceedings of 2nd International Conference on Travel Medicine. Atlanta, Georgia. Centers for Disease Control (m press).
Twins with different fathers SIR,-Most mammals discharge several ova during ovulation, resulting in multiple births. In women a single ovum discharge is the norm since their ovaries generally alternate egg production. However, there are exceptions, the result being dizygotic (DZ) twins for example, and if a woman has intercourse with different men during polyovulation twins with different fathers would be possible. Archerl in 1810 observed radically different twins (one white, the other mulatto) with two different fathers. Geyer’ in 1940 identified DZ twins with different fathers by red cell antigen typing, these findings being endorsed by HLA typing.3
64
percentage of patients delivering withm 8 h of induction was 36 % in group 1 and 73% in group 2 and the misoprostol doses required averaged 162 pg and 188 ng, respectively. More than half the
patients responded
Cytogenetic markers on chromosome 18 in alleged father (A), mother (B), son (D), and daughter (E). Alul-Giemsa-resistant chromatin present on both chromosomes 188 alleged father is shared by son but not by daughter. Size of Y in alleged father is apparently present in son Legal father (C) refused to in
participate We report a case of DZ twins of different sex, where the alleged father refused to take responsibility for the children, claiming they belonged to the legal father. The legal father refused to take part in a paternity determination. Informative cytogenetic markers were seen in the alleged father and the son. The most remarkable observation in the alleged father was the presence of restriction endonuclease AluI resistant chromatin’ on both chromosomes 18. The son had one positive chromosome 18 whereas both of the daughter’s chromosomes 18 were negative (figure). The alleged father was typed ss and the daughter was SS, suggesting that he could not be the biological father of the daughter, but the unusual heteromorphic markers found in the alleged father were shared by the son. The size of the Y chromosome is a variable anthropological trait in man.’ The alleged father and the son both have the same size Y chromosome. Once the alleged father was informed of these results, he immediately refused DNA fingerprinting. It seemed that the mother had had intercourse with two different men around the time of ovulation, and she admitted to this during
counselling. Department of Laboratories, Long Island College HospitalSUNY Health Science Center, Brooklyn, NY 11201, USA
1. Archer J. Facts illustrating a disease peculiar to the female children of negro slaves. Med Reposit 1810, 1: 319-23 2 Geyer E. Ein Zwillings parchen mit Zwei Vatem (Nachgewiesence Uberschwangerung beim Menschen). Arch Rassenbiol 1940, 34: 226 3. Terasaki PI, Gjertson D, Bemoco D, et al Twins with two different fathers identified by HLA. N Engl JMed 1978; 299: 590-92. 4. Verma RS, Babu A. Human chromosomes manual of basic technique New York: Pergamon, 1989: 93-95. 5. Verma RS, Pandey RP. Nonrandom distribution of various sizes of human Y chromosomes in different ethnic group Ann Hum Biol 1987; 14: 271-76
Misoprostol to induce labour SiR,—We have done two studies’2 that corroborate the efficacy of vaginal misoprostol in inducing uterine contractions during the third trimester of pregnancy-a dose-finding study and a comparative trial of misoprostol and oxytocin. In the dose-ranging study (published in a journal covered by Current Contents and summarised very briefly here) patients were at gestational age 28-36 weeks (n = 11) or more than 36 weeks (n = 45), and induction of labour was medically indicated. An initial dose of 50 ug, in the posterior vaginal fornix, was followed by increasing doses of 50 Ilg every 2 h until satisfactory uterine activity was achieved. The maximum permitted was 600 Ilg. Induction was considered successful if the patient delivered within 8 h. 36% and 69% of women in groups 1 and 2, respectively, were nulliparous. The
single 50
pg dose. 3 women
J A Fernández Hospital, University of Buenos Aires,
reported
MIGUEL MARGULIES GERMAN CAMPOS PÉREZ LILIANA S. VOTO
1119-Beunos Aires, Argentina; and School of Medicine, Universidad Austral de Chile
1. Margulies M, Voto LS, Catuzzi P, Uranga Imaz F. Inducción del trabajo de parto con un análogo de la PgE1. Un estudio abierto, no comparativo, de hallazgo de dosis. Prensa Méd Arg 1991; 78: 9-13 2. Campos Pérez GA, Margulies M, Ortega I, Voto LS. Induction of labor with Misoprostol, a PgE1 analog: a comparative study. Proceedings of 2nd European Congress on Prostaglandins in Reproduction (The Hague, Netherlands, April 30-May 3, 1991).
Oral R. S. VERMA S. LUKE P. DHAWAN
to a
diarrhoea and hot flushes but no adverse effects on the fetus or baby were observed. The second study was a randomised, controlled trial in 64 patients with a single fetus and intact membranes and in whom induction was necessary for medical or obstetric indications.2 In 33 patients a tablet containing 50 ng misoprostol was placed in the posterior fornix ; the other 31 were given intravenous oxytocin. Successful induction was defmed as vaginal delivery within 24 h from the moment when three contractions in 10 min were detected. Gestational age and Bishop score at entry were not significantly different in the misoprostol and oxytocin groups. In the misoprostol group, induction was successful in 26 (79%) patients; 1 patient was delivered by caesarean section because of fetal distress. In the oxytocin group, induction was successful in 19 (62 %), and 8 women had caesarean section, 5 of them for failure of labour to progress and 3 because of fetal distress. Induction-to-delivery interval was 407 (SD 265) min in the misoprostol group and 577 (605) in the oxytocin group (p = 0-2). No differences were found in birthweight or Apgar scores. Side-effects were not observed, but polysystole (more than 5 contractions in 10 min) was more frequent in the misoprostol group (17%) than in the oxytocin group (12 %); however, no fetal distress was associated with this condition in either group. Our findings suggest that misoprostol is effective in the induction of labour in the third trimester of gestation, with few side-effects on the mother and no apparent adverse effects on the fetus or newborn baby. In our population efficacy of misoprostol was comparable with that of oxytocin.
immunosuppression for multiple sclerosis
SIR,-With due respect for the efforts of the initial investigators and Professor Yudkin and colleagues’ (Oct 26, p 1051) overview indicating a marginal benefit of azathioprine for multiple sclerosis, I suggest that the treatment programmes were not adequate. First, most patients were treated with 2-25 mg/kg daily; 3 mg/kg daily was used in only one of the groups evaluated at 2 years (and in none of those evaluated at 3 years), and that group consisted of only 10% (21/206) of the patients treated for 2 years. Second, only two of the trial groups attempted to use a biological indicator of azathioprine effect, and they used the wrong oneleucocyte count, presumably for efficacy and/or safety. The leucocyte count is an archaic value-that should be proscribedconsisting mainly of two totally different cell populations, which during immunosuppression treatment can have opposite implications. I customise long-term immunosuppression for each patient. 1-1For safety I do not allow the neutrophils (granulocytes) to drop below 2000/1; for efficacy I try to reduce the total lymphocyte population to below 700/1 ( < 400 is acceptable), if necessary by carefully raising the dose with monitoring of the neutrophil count. The lymphocytes themselves are a mixed population consisting of only some so-called bad ones, but this lower-than-700 goal and imprecise rationale seem to have correlated with clinical benefit in the various neuromuscular diseases that have been treated (eg, polymyositis/dermatomyositis, myasthenia gravis, and chronic dysimmune neuropathies). Third, although the preferred drug for long-term treatment of dysimmune neuromuscular diseases is controversial, since about
