983

fenoterol, and this general increase (if it exists) does

not seem to

for the sudden upsurge in asthma deaths in New Zealand that began when fenoterol was introduced in 1976. account

CARL BURGESS

Department of Medicine, Wellington School of Medicine,

JULIAN CRANE NEIL PEARCE RICHARD BEASLEY

PO Box 7343, Wellington, New Zealand

1. Trembath PW, Greenacre JK, Anderson M, et al. Comparison of four weeks’ treatment with fenoterol and terbutaline aerosols in adult asthmatics. J Allergy Clin Immunol 1979; 63: 395-400. 2. Keating G, Mitchell EA, Jackson R, et al. Trends in sales of drugs for asthma in New Zealand, Australia, and the United Kingdom, 1975-81. Br Med J 1984; 289: 348-51. 3. Sears MR, Beaglehole R. Ashtma mortality: a review of recent experience in New Zealand. J Allergy Clin Immunol 1987; 80: 319-25.

Fat embolism after

lipid emulsion infusion

SIR,-Dr Estebe and Dr Malledant (March 16,

p

673) report

postoperative fat embolism (day 20) linked to rapid infusion of 500 H soybean oil lipid solution (’Intralipid’). They do not fully describe the details of their case or explain the reasons for the very high rate of infusion. We would put the case into perspective, in view of current knowledge of the safety and tolerance of intralipid. The recommended rate of infusion is 500 ml intralipid 20% over not less than 5 h, and of intralipid 10% over not less than 3 h. Precautions in the use of intralipid should be taken when fat metabolism may be disturbed, and in renal insufficiency, hepatic insufficiency, uncompensated diabetes, metabolic disorders, and sepsis. In patients with such conditions and in longlasting administration, fat elimination should be checked daily by a simple test. Fat overload can occur within 24 h, the symptoms of which include fever, thrombocytopenia, jaundice, and internal haemorrhage. Estebe and Malledant cite two papers in support of fat embolism complication of lipid emulsion. In one of these Goulon et all referred to an emulsion of cotton seed oil and soybean phospholipids as an emulsifier, but this is not relevant to intralipid, a soybean preparation developed much earlier, with egg-yolk phospholipids as the emulsifying agent. Intralipid was the first non-toxic fat emulsion. In the second report, Horisberger described a 32-year-old woman receiving fat 2-5 g/kg daily. Pulmonary symptoms featured more prominently in this patient, although the concluding statement suggests that the event was "probably provoked by intravascular aggregation of cellular elements rather than by fat embolism". Although precautions in the use of fat emulsions should be borne in mind, over sixty million infusions of intralipid have been given, with a very low rate of adverse events. Intralipid is a valuable source of energy and essential fatty acids in patients needing parenteral nutrition. as a

Kabi Pharmacia,

Knowlhill, Milton Keynes MK5 8PH, UK

M. McCRACKEN

1. Goulon M, Barois A, Grosbuis 2

S, Schortgen G. Embolie Graisseuse après perfusions répétées d’émulsions lipidiques. Nouv Presse Méd 1974; 3: 13-18. Honsberger B. Schwere pulmonale and cerebrale Zirkulationsstorungen nach hoch dosierter parenteraler Zufuhr einer Fettemulsion. Ein Fall einer aussegewohnlichen terapeutischen Komplikation. Schweiz Med Wschr 1966; 96: 1065-69.

three women in whom DES exposure probably caused hyperprolactinaemia after birth. In the first patient menarche was followed by irregular menses. At age 20 she had a clear-cell carcinoma of the vagina and secondary amenorrhoea and hyperprolactinaemia (prolacnn [PRL] 1200 mU/1; normal < 300). She was also mentally retarded and grossly obese. The second patient was oligophrenic. Epilepsy developed coincidentally with menarche. At age 21 she had hyperprolactinaemia (PRL 50 µg/1; normal 22) with galactorrhoea. On computed tomographic (CT) scanning the sella was slightly enlarged and partly empty. The third patient had secondary amenorrhoea, galactorrhoea, and hyperprolactinaemia (PRL 500 µg/1) after withdrawal from 10 years’ use of oral contraceptives. On CT scan the sella was enlarged and the floor eroded. Pregnancy was induced by bromocriptine. During pregnancy PRL concentrations were twice as high as is normal in pregnancy. Toxaemia developed and she gave birth by caesarean section to a son with a large omphalocele. Although three patients do not prove causality I propose that exposure to DES may lead to a disturbance of PRL secretion. In the three patients, hyperprolactinaemia was identified on the basis of lactotroph hyperplasia and/or (micro) prolactinoma. My observations also suggest that DES exposure may impair brain development. I believe that endocrine and neurological investigation of DES-exposed offspring is warranted.

prenatal

Departments of Endocrinology and Academic Medical Centre, 1105 AZ Amsterdam, Netherlands

Psychiatry,

J. ASSIES

1. Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med

1971, 284: 878-81. 2. Vessey MP, Fairweather DVI, Norman-Smith B, Buckley J. A randomized double-blind controlled trial of the value of stilboestrol therapy in pregnancy: long-term follow-up of mothers and their offspring. Br J Obstet Gynecol 1983; 90: 1007-17. 3. Wu CH, Mangan CE, Burtnett M, Mikhail G. Plasma hormones in DES-exposed females. Obstet Gynecol 1980; 55: 157-62. 4. Menczer J, Dilitzky M, Ben-Baruch G, Modan M. Primary infertility in women exposed to diethylstilboestrol in utero. BrJ Obstet Gynecol 1986; 93: 503-07. 5. Ehrhardt AA, Meyer-Bahlburg HFL, Rosen LR, et al. The development of gender-related behaviour in females following prenatal exposure to diethylstilbestrol (DES). Hormones Behav 1989; 23: 526-41.

Epidemic tuberculosis in north Lebanon SIR,- The long civil war in Lebanon has caused poverty and severely disrupted health services. Evidence now suggests these conditions have led to an epidemic of tuberculosis.l Between 1980 and 1984 skin-test surveys of children in the districts of Akkar and Zgharta2,3pointed to a low exposure both to tubercle bacilli and to other environmental mycobacteria, and clinical accounts indicated only isolated instances of the disease.’ A chest clinic in Tripoli, reporting 25-35 cases per year in the early 1980s, records 325 cases in 1989, and over 400 in 1990 (figure). About 80% of cases are among adults and 20% among children. Drugs are scarce, most patients remain untreated, and very few children have received BCG vaccination. In October, 1990, a survey of 432 schoolchildren was done in some villages of Akkar that were studied earlier. There have been significant increases in tuberculin positivity rates:

Hyperprolactinaemia in diethylstilboestrol-exposed women SIR,- The

use

of the

synthetic oestrogen diethylstilboestrol

(DES) in women during pregnancy has been associated with cancer and developmental abnormalities in the lower urogenital tract in behaviour and even cause psychiatric disease (depression, anxiety).2,3 Although the frequency of menstrual irregularity and primary infertility among DES-exposed women is significantly higher than in the general population, surprisingly little systemic

There was no evidence of an increase in tuberculin positivity over the years of the earlier study, so the change has happened since 1984. There is a pressing need for a BCG vaccination programme for all children in the region. The development of an infrastructure to report cases of tuberculosis, to make short-course chemotherapy available, and to provide follow-up is also a priority. Security difficulties continue to restrict the work of government and non-government organisations in developing basic primary health

evaluation of their endocrine system has been done.4,5 I report

care.

their female and male offspring.’ Early exposure of the fetus to oestrogen can also determine subsequent temperament and