degree of absorption from the gastrointestinal tract, its interactions with other metals and miscellaneous cellular components,’ and its reduction intracellularly to the weakly active inhibitor of Na+, K+-ATPase, vanadyl.6 Nonetheless, the dose is about fifty times the amount of vanadium consumed daily in the normal American diet.7 Parenteral administration of vanadate increases the toxicity and morbidity of ouabain in mice and rabbits.8
The use of vanadate seems to be confined to a small group of doctors specialising in unconventional therapy with vitamins and minerals. This practice may not be restricted to Finland. Most patients seeking such vanadate-containing therapy will be elderly and will be at risk of serious drug interaction if they are taking digitalis. Digitalis toxicity is always dangerous and frequently fatal.
Department of Pharmacology and Toxicology, University of Kuopio, SF-70101 Kuopio 10, Finland
EWEN MACDONALD KAISA HELLEVUO
TRANSPLACENTAL CARCINOGENESIS (ADRENOCORTICAL CARCINOMA) ASSOCIATED WITH HYDROXYPROGESTERONE HEXANOATE
SIR,-Human transplacental carcinogenesis was first convincingly demonstrated by Herbst et al,1 who reported that large doses of stilboestrol given to pregnant women led to adenocarcinoma of the vagina in daughters of those pregnancies 14-22 years later. Drugs anecdotally reported to be associated with cancer in children who were exposed in utero include phenytoin and an oestrogen contraceptive2 and hormonal treatment for sterility.3 We describe here adrenocortical carcinoma in the infant daughter of a woman who received hydroxyprogesterone hexanoate during the first trimester.
At the age of 2 months a baby girl was noted to have two lumps on her head, which later regressed. At 3 months old a lump appeared in her left groin, and subsequently subcutaneous nodules appeared on her trunk, face, scalp, neck, and limbs. She also had enlarged firm lymph-nodes in the neck, axillae, and groins and a mass in the right hypochondrium. Investigations at age 51/2 months revealed multiple lung and skeletal metastases from a large tumour in the right renal area, surrounding the right kidney and extending into the lower thorax. Patchy calcification was present within the tumour. Biopsy of an inguinal node showed complete replacement by highly cellular malignant tumour consistent with adrenal carcinoma. The cells formed narrow trabeculae and small groups without a lumen, and had clear round or ovoid nuclei with little mitotic activity and variable amounts of vacuolated cytoplasm. Bone marrow aspirate, urine catecholamine excretion, and serum a-fetoprotein, and ß-subunit human chorionic gonadotropin levels were normal.
As cure seemed impossible, only symptomatic treatment was given. She progressed poorly but remained lively and fairly well despite the steadily increasing size of her primary tumour and metastases. At first her genitalia appeared normal, but by the age of 11 months she had clitoral enlargement, and by 13 months pubic hair. Her serum testosterone levels were raised at 17 and 8 . 8 nmol/l and her androstenedione at 37-7 nmol/l. Her serum dehydro- epiandrostenedione sulphate level was normal at 1 .3 umol/l. Her chromosome karyotype was 46,XX. She died aged 17 months.
Before conception of the patient her mother had had termination of a pregnancy and three miscarriages. To prevent another miscarriage she was given 500 mg hydroxyprogesterone hexanoate
(‘Primolut Depot’, now called ‘Proluton Depot’) intramuscularly weekly from the second to the 11th week of the pregnancy. The only additional point of possible significance in the family history was that both of the mother’s elder brothers and possibly one of her four younger brothers had cerebellar degeneration; her sister was unaffected but the condition was thought to have been inherited as an autosomal recessive.
Proluton depot given in early pregnancy has been associated with a variety of defects4 in babies, including virilisation of a female infant and ambiguous genitalia in a male,5 although one study of 150 pregnancies showed no increase in malformations after maternal proluton in a comparison with controls.6
| JILLIAN R. MANN A. H. CAMERON | |
|---|---|
| P. GORNALL | |
| The Children's Hospital, Ladywood Middleway, | P. H. W. RAYNER |
| Ladywood, Birmingham B16 8ET | K. J. SHAH |
PNEUMONIA DUE TO SALMONELLA CHOLERAESUIS IN INFANTS IN PAPUA NEW GUINEA
SIR,-The major causative agents of acute pneumonia in infants in Papua New Guinea (PNG) are Haemophilus influenzae and Streptococcus pneumoniae.7 While results in our own blood culture series (unpublished) agree with this finding the isolation of Salmonella choleraesuis var kunzendorf from several children with clinical and radiologically confirmed pneumonia has highlighted the need for appropriate antibiotic coverage and the recognition of less common pathogens. In PNG standard treatment regimens are followed. Children with moderate pneumonia are treated with benzylpenicillin and those with severe pneumonia (including cyanosis and/or heart failure) are given chloramphenicol.
Four children, three female and one male, aged between one and three years were admitted to the Goroka Base Hospital with pneumonia (see table). Three were underweight compared with the Harvard mean and one of these was marasmic. Chest X-rays showed lobar consolidation and perihilar infiltration in two cases each. All were pyrexial on admission and two had a maculopapular rash. Three of four had diarrhoea and one of these had frank blood in the stools. Two had vomiting and required intravenous rehydration. Three were treated intially with benzylpenicillin with no clinical response and then changed to chloramphenicol. Clinical recovery varied from 5 to 22 days; three of the four infants were discharged well and one absconded.
S choleraesuis var kunzendorf was cultured from blood collected from each infant immediately after admission. The same organism was isolated from the nasopharyngeal aspirate and faeces of one of three infants from whom this material was collected. In each instance chloramphenicol therapy had been started. The identifi- cation of all strains has been confirmed by the Salmonella Reference Laboratory, Institute of Medical and Veterinary Science, Adelaide.
Pneumonia due to S choleraesuis has been studied by Saphra et al.8,9 No childhood infections due to this organism were reported until 1960, and little further information was available until the recent report by Weissbluth et al. 10
Bacteraemia occurs in most S choleraesuis infections and, in keeping with its unusual invasive characteristics, localised
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