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

65

1981have found single-dose daily oral cyclophosphamide starting 2 mg/kg to be more effectiveand have no worse side-effects, than my previous use of 3 mg/kg daily azathioprine (each given with high single-dose, alternate dayl-3 prednisone, which raises circulating neutrophil counts and helps to depress lymphocyte counts). The cyclophosphamide dose is adjusted down or up according to the 2000/700 guidelines. Important safety adjuncts with oral cyclophosphamide include a weekly differentiated bloodcount and the patient drinking at least 36 litres of liquid daily. Because the opportunity for substantial benefit of oral immunosuppression in multiple sclerosis patients might have been missed, I suggest a trial with chronic (1-3 years) oral at

cyclophosphamide (plus high single-dose alternate-day prednisone) according to these indices. (The Canadian cooperative 22-week trial including 1-5-2 mg/kg oral cyclophosphamide" and another oral trials used the outmoded leucocyte count, and recent intravenous cyclophosphamide studies6,7have used only "white blood cell count".) University of Southern California, Neuromuscular Center, Los Angeles, California 90017, USA

W. KING ENGEL

Engel WK, Dalakas MC. Treatment of neuromuscular diseases. In. Wiederholt WC, ed. Therapy for neurologic disorders. New York: Wiley, 1982: 51-101. 2. Engel WK. Treating "untreatable" neuromuscular disease patients. Muscle Nerve 1

1986; 9: 95. DC, Engel WK. Remarkable

3. De Vivo

4.

recovery of

a

steroid

responsive

recurrent

polyneuropathy J Neurol Neurosurg Psychiatry 1970; 33: 62-69. The Canadian Cooperative Multiple Sclerosis Study Group. The Canadian cooperative tnal of cyclophosphamide and plasma exchange in progressive multiple

sclerosis Lancet 1991; 337: 441-46. 5. Khatn BO, McQuillen MD, Hoffmann RG, Harrington GJ, Schmoll D. Plasma exchange in chronic progressive multiple sclerosis: a long-term study. Neurology

1991, 41: 409-14. 6. Mackin GA, Weiner HL, Orav JA, et al. Cyclophosphamide/ACTH plus maintenance cyclophosphamide boosters in progressive MS: final report of the Northeast Cooperative MS Treatment Group I. Neurology 1991; 41: 147. 7. Likosky WH. Experience with cyclophosphamide in multiple sclerosis the cons. Neurology 1988; 38: 14-18

Diagnosis of urinary tract infection in children SIR,-I would point out some drawbacks to Dr Vickers and colleagues’ report (Sept 28, p 767). With their definition of urinary tract infection (UTI)-the presence of both a positive culture (> 105 colony-forming units/ml of one organism) and positive microscopy (8 organisms per high-power field or 100 organisms per grid)—they had 24 UTIs in 342 children. 13 other urine specimens had a pure growth of one organism that subsequently proved negative on repeat culture that was done because the initial microscopy was negative. There were therefore 13 false-positive cultures on the initial urine specimens in conjunction with true negative microscopy. What is not controlled for in this study is the possibility of false-positive microscopy in conjunction with a false-positive urine culture. If 13 of 37 specimens were known to be initial false positives on culture, then how do we know whether 13 of the remaining 24 were not also false-positive cultures but had enough bacteria to result in positive microscopy? Since urine specimens with this possibility were not repeated, the question cannot be conclusively answered by this study. I think Vickers and colleagues’ study warrants this question being looked at again, perhaps with a more reliable collection method such as suprapubic aspiration or urethral catheterisation in the young child, to reduce the possibility of false-positive culture and microscopy. Pediatrics, UAH Medical Clinics,

BOYCE A. HORNBERGER

Huntsville, Alabama 35801, USA

SlR,—We agree with Dr Sheppard and Dr Kelly (Nov 2, p 1144) that close collaboration between clinicians and microbiologists is essential for an accurate diagnosis of urinary tract infection (UTI). The first requirement is correct sampling and transportation, followed by careful microscopy and culture. Accurate diagnosis is

especially important

in

infancy.’

It is

important

babies who should be investigated for urinary

to

identify those anomalies,

tract

especially vesicoureteric reflux, without subjecting those who have false-positive tests to unnecessary procedures. Suprapubic aspiration or urine is regarded as the gold standard of diagnostic tests for UTI. Aronson and colleagues2 compared such sampling with simultaneously obtained clean-bag specimens in 120 patients, and noted 31 false-positive and 8 false-negative tests in samples from the bag. The recommendationto use ultrasonography to show urine in the bladder of newborn babies before suprapubic aspiration improved the success rate of first attempt from 36% to 100%. We have used the same technique in infants admitted for febrile illness. One of us (N. A.) has taught all paediatric residents (senior house officers) to use a ward-based ultrasound scanner to help with the suprapubic aspiration technique. Previously untrained staff find this easy to do, which increases the success rate and avoids upset to infants, parents, or staff by having to repeat the test and uncertainties of less accurate collection techniques. During four weeks in October and November, 1991, we obtained urine by suprapubic aspiration in 35 male and 26 female babies; 25 were newborn, and 36 were aged 1-16 months. 11 specimens (from 9 boys and 2 girls) yielded a positive culture. All isolates were coliforms; bacterial count was greater than 105/ml in 4 and less than 105/ml in 7. These findings confirm that low bacterial counts in urine specimens from children may be clinically significant and should not always be dismissed as contaminants. Dr Vickers and colleagues (Sept 14, p 674) misunderstood a previous paper on low bacterial counts in boys.’ Of the 73 boys investigated, 12 had counts of 104/ml on presentation to their general practitioners. 4 of them subsequently proved to have radiological abnormalities-the same percentage as boys who presented with counts of 105/ml. The association of low bacterial counts with radiological abnormalities has also been reported by Cohen.5 Department of Paediatrics and Child Health, and Public Health Laboratory, St Mary’s Hospital, Portsmouth P03 6AD, UK

NICOLA AUSTIN ROSALIND MASKELL RICHARD J. HALLETT

Working Group of the Royal College of Physicians. Guidelines of the management of acute urinary tract infection in childhood. J R Coll Phys Lond 1991; 25: 36 2. Aronson AS, Gustafen B, Svenningsen NW. Combined suprapubic aspiration and clean-voided urine examination in infants and children Acta Paediatr Scand 1973; 1.

62: 396-400. 3.

O’Callaghan C, McDougall PN. Successful suprapubic aspiration of urine. Arch Dis

Child 1987; 62: 1072-73. RJ, Paed L, Maskell R. Urinary infection in boys: a three year prospective study Lancet 1976; ii: 1107-10. 5. Cohen M. The first urinary tract infection in male children Am J Dis Child 1976, 130:

4. Hallett

810-13.

Neonatal bilirubin SiR,—Your Nov 16 editorial notes the lack of conclusive data on association between moderately increased neonatal bilirubin concentrations and inferior intelligence; our results support that view.1 However, your conclusion that current treatment policies "only achieve inefficient removal of a potentially helpful antioxidant" may be misleading. Current evidence on a beneficial role of bilirubin as an antioxidant is indirect and retrospectiveor has been obtained in vitro.3 Phototherapy is most effective in infants with substantial hyperbilirubinaemia but it works gradually, and once bilirubin concentrations exceed 375 jjmol/1 prolonged phototherapy treatment may be necessary. Advice suggesting that early phototherapy should be avoided may therefore place the infant at greater risk of extended exposure to potentially harmful levels of bilirubin and of prolonged hospital stay. An alternative strategy may soon be possible by using methods that identify, within a few hours of birth, infants at high risk of hyperbilirubinaemia. In the USA, the NICHHD Neonatal Research Network has launched a multicentre study to find out if hyperbilirubinaemia can be predicted by non-invasive measurement of respiratory carbon monoxide excretion.4 If we could estimate the risk of clinically important neonatal jaundice developing we could not only allow early discharge from hospital but also be at the first stage of a strategy of chemoprevention.57 In the meantime, we can resort to fibreoptic technology for delivery of high-intensity phototherapy. Fibreoptic an