continued for 5 weeks until the long amenorrhoea aroused suspicion and a urine pregnancy test was positive. At 21 weeks’ gestation an ultrasound scan confirmed the gestational age by the last normal menstrual period. No fetal abnormality was detected. Pregnancy was otherwise unremarkable. A girl was bom by caesarean section (for failure to progress at 39 weeks). Gestational age was confirmed by Dubowitz score. Birthweight was 3-55 kg (70th percentile). Head circumference was at the 25th percentile and length at the 50th percentile. The baby had an asymmetric chest, thoracic scoliosis, absent left thumb, foreshortened left forearm, and left elbow contracture. Radiological studies revealed fusion of the ribs on the left, butterfly vertebrae in the thoracic and lumbar spine, and left radial aplasia. A lower oesophageal stricture required surgical correction. The family history was unremarkable and the parents were nonconsanguinous. Karyotype (46,XX) and G-banding studies were normal. Diepoxybutane-induced chromosome breakage analysis ruled out Fanconi anaemia. Two medications were taken during the first trimester at the time of embryogenesis. Dextroamphetamine is rated category C (US Food and Drug Administration definitions)—ie, no controlled studies in women or laboratory animals are available so the drug should be given "only if the potential benefit justifies the potential risk to the fetus". Lovastatin, on the other hand, is category X-ie, "studies in animals or human beings have demonstrated fetal abnormalities" and "the drug is contraindicated in women who are or may become pregnant". We do not know if the association between VATER and lovastatin was causal or chance in this case. However, the drug was taken in a critical period (between 4 and 9 weeks of embryogenesis). According to the Physician’s Desk Reference (1992), lovastatin has produced skeletal malformations in rats (at amounts 500 times greater than the maximum recommended dose). There are no data in pregnant women. Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA









and Paediatrics,

University Hospital Gasthuisberg, B-3000 Leuven, Belgium

1. De

Zegher F, Spitz B, Devlieger H. Prenatal treatment with thyrotrophin releasing hormone to prevent neonatal respiratory distress. Arch Dis Child 1992, 67: 450-54. 2. Dawes GS, Moulden M, Redman CWG. The advantages of computerized fetal heart rate analysis. J Perinat Med 1991; 19: 39-45.

Improvement of patient with amyotrophic lateral sclerosis given ceftriaxone man had a history of progressive symptoms over 221 years, beginning with left arm weakness and pronounced fasciculations. An X-ray of the neck revealed osteophytes and stenosis of C4-6 and an exploration of the area with fusion of C5-C6 had been done 121 years previously. Postoperatively the patient had a respiratory arrest and left vocal cord paralysis. This was followed by generalised muscle weakness, worse on the left, and he often fell when walking. His speech was garbled and of low volume. He could not shave himself, get out of a chair, dress himself, or arise from bed without assistance and he had

neurological on

SIR,-Professor Ballard and colleagues (Feb 29, p 510) report that the addition of thyrotropin-releasing hormone (TRH) to prenatal glucocorticoid administration further reduces neonatal respiratory disease in very-low-birthweight infants. TRH exerts multiple actions on several fetal organ systems, possibly including the cardiovascular system. We therefore investigated the effect of maternal TRH administration on the heart rate of preterm fetuses. A cardiotocographic record for 30 min was obtained for 40 fetuses between 25 and 34 weeks’ gestation, just before and from 45 to 75 min after maternal intravenous bolus injection of 400 ug TRH in saline (UCB, Belgium; n 26) or saline (n = 14). The fetuses were studied in standardised conditions: all observations were completed between 9 am and 6 pm, 3 h after a meal. Women with juvenile diabetes, preterm premature rupture of the membranes, progressive labour, or cardiotocographic signs of fetal distress were =

Departments of Obstetrics and Gynaecology,


SIR,-A 69-year-old


Effects of thyrotropin-releasing hormone fetal heart rate

excluded. By connecting the cardiotocograph to the computerised Oxford Sonicaid fetal heart rate monitoring system, on-line analysis was obtained for the fetal baseline heart rate, acceleration patterns, and long-term heart rate variability.2 Paired Student’s t-test was used for statistical analysis. The two study groups did not differ with respect to gestational age, pathology, or medical treatment. From 45 to 75 min after TRH administration a significant fall in baseline heart rate was observed, together with a significant increase in heart rate accelerations and long-term variability (table). No significant changes were detected in the control group. The results indicate that maternal TRH administration has substantial effects on the fetal cardiovascular system within 1 h. Whether these effects are evoked through endocrine, neurotransmitter, or other pathways is unclear. The importance of the cardiovascular changes in relation to the fetal lung maturation is also unknown. Obstetricians planning to use TRH should take into account TRH-induced cardiotocographic changes in their subsequent assessment of the treated fetus.

difficulty swallowing. He was seen by several neurologists who confirmed the diagnosis of amyotrophic lateral sclerosis (ALS) and neurophysiological studies confirmed this. Magnetic resonance imaging scans of brain and cord were negative. Serological tests for Lyme disease and syphilis were negative. The patient was put on ceftriaxone in April, 1992, at the suggestion of Dr Malcolm Foster (Jacksonville, Florida) who had heard of a patient who had improved on this treatment. Our patient can now sit up, drive a car, shave himself, speak better, and swallow without difficulty, having been on intravenous ceftriaxone 2 g per day for 3 weeks. We plan to maintain this therapy because the other patient had relapsed when ceftriaxone was stopped and had responded again once the drug was restarted. This is the second anecdotal case of ALS improving on this third-generation cephalosporin. It is difficult to see why ceftriaxone should help in ALS except that it gets into the central nervous system in high concentrations and can act as a chelating agent, perhaps removing the microcalcifications as seen in ALS. There remains the possibility that this patient has seronegative Lyme disease; however, repeated ELISA and western blot tests on serum have been found to be negative by two reliable laboratories. This improvement has been observed by three clinicians and I do not believe that it is a placebo effect. The response may be only temporary but the drug seems worth trying. St Michael’s Medical Center, Newark, New Jersey 07102, USA, and New Jersey Medical School


Effects of thyrotropin-releasing hormone on fetal heart rate.

1417 continued for 5 weeks until the long amenorrhoea aroused suspicion and a urine pregnancy test was positive. At 21 weeks’ gestation an ultrasound...
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