PERINATAL MORTALITY

777 for the discrepancy between our results and those of the manufacturers. Differences in technique in estimating the M.l.C. are no doubt also of importance. The mean annual temperature in Christchurch is about 11°C, and storage of the containers at a relatively low temperature may have been a factor allowing the organism to survive. Regardless of the explanation of these anomalies, we are satisfied, after repeated testing, that the organism originated in the antiseptic. We should like to emphasise the importance of routine testing of antiseptic solutions. We have introduced a medium of trypticase/soy-broth with 1 % glucose, phenol-red indicator, and 0-5% Tween 80’ for testing antiseptic solutions containing hexachlorophane. account

P. H. PALMER L. M. MCCRACKEN.

THE CHOROID PLEXUS IN AFRICAN SLEEPING-SICKNESS

frequent first symptom of sleepingfrontal headache; African patients often recognise the disease from this. Le Port1 attributed the headache to cerebral hypertension caused by swelling of the choroid plexus as it passes through the foramina, thereby blocking the passage of cerebrospinal fluid from the ventricles. In experimentally infected rats we have confirmed that vessels of the ventricular choroid plexus rapidly become engorged; with some strains of trypanosomes this may happen within five days of infection. By microscopical examination of impression smears of choroid plexus we have demonstrated amastigotes (Leishman-Donovan bodies) similar to those found in other organs,2but the typical form in smears of the choroid plexus appears to be the spheromastigote (flagellated L.D. body). Serial sections of choroid plexus show that a few of the capillaries are completely blocked with large numbers of bodies with the appearance of amastigotes. We believe we have discovered a hitherto undescribed phase in the life-cycle of the sleeping-sickness trypanosome, and we are investigating further the implications of this finding for understanding the pathogenesis and therapy of the disease. SiR,łThe

most

a severe

London School of Hygiene and

W. E. ORMEROD S. VENKATESAN.

Tropical Medicine, London WC1E 7HT.

BETA-BLOCKING EFFECT OF PRACTOLOL IN ASTHMATICS

SiR,-The report by Dr. Bernecker and Dr. Roetscher (Sept. 26, p. 662) that practolol, when given by inhalation, causes a fall in vital capacity and peak expiratory flow in some asthmatic subjects is of considerable interest. The rapid reversal of the fall in ventilation by isoprenaline contrasts with the observations reported by McNeill3 that the fall in ventilation produced by intravenous propranolol in similar subjects was not reversible with iso-

prenaline. Taken

together, these observations suggest that either not affecting the beta-receptor sites on bronchial smooth muscle and its effect on ventilation is non-specific, or the beta-receptor blockade produced by practolol on practolol is

bronchial smooth muscle is

capable

of

being stimulated by iso_

prenaline. Although we agree practolol in patients

that caution is required in the use of with obstructive airways disease, it would appear to be a safer preparation to use than propranolol in view of the rapid reversal of its effect by isoorenaline. Respiratory Diseases Unit, Western Infirmary, Glasgow W.1.

JAMES W. KERR K. R. PATEL.

PERINATAL MORTALITY

Microbiology Unit, Christchurch Hospit al, New Zealand.

sickness is

receptor site is still

"

surmountable

"

4 and the

1. Le Port, R. Bull med. Katanga, 1935, 12, 41. 2. Soltys, M. A., Woo, P. Trans. R. Soc. trop. Med. Hyg. 1969, 63, 490. 3. McNeill, R. S. Lancet, 1964, ii, 1102. 4. Maxwell, R. A., Plummer, A. J., Povalski, H., Schneider, F. J. Pharmac. 1960, 129, 24.

SIR,-Many authors

of papers

on

perinatal mortality

express disbelief that the U.S.A., with its excellent standard of obstetrics, has a higher perinatal-mortality rate than 17 other countries. Some say this discrepancy is due to the different methods of recording statistics. Could it not be that these statistics might just be true ? Most writers refer to the booklet entitled International Comparison of Perinatal Infant Mortality: the United States and Six West European Countries, published by the U.S. Department of Health, Education, and Welfare in 1967. In this manual the U.S.A. is compared with Denmark, England and Wales, the Netherlands, Norway, Scotland, and Sweden. The statistics usually quoted are: (1) in 1964 the infant mortality in the U.S.A. exceeded that of 17 other advanced countries; (2) compared with the 6 European nations the infant-mortality rate in the U.S.A. in 1935 was in the middle of the group, whereas in 1964 it had the highest rate; (3) there was a general fall in the infant-mortality rate in all 7 nations, but since 1950 the fall has been less in the U.S.A. than in the other 6 nations; (4) mortality in the first 24 hours of life was greater in the U.S.A. than in the other 6 countries; and (5) the mortality of infants 1-6 days old was higher in the U.S.A. than in most of the other 6 countries in 1964. The following statistics found in the booklet, though less often publicised, might also be important: (1) the frequency of caesarean section is highest in the U.S.A.; (2) the frequency of episiotomy is highest in the U.S.A. (67-4% of deliveries); and (3) the " place of delivery " varies from country to country (in the U.S.A. 97% of deliveries are in hospital, compared with 29% in the Netherlands). In reviewing the neonatal deaths by causes the following interesting observations are made, but for some reason are seldom noted. Firstly, in the Netherlands, where deliveries were mostly in the home, the deaths due to injuries were high (27-0%, compared with 12-8% in the U.S.A). However, deaths due to asphyxia and atelectasis in the Netherlands were low (10-8%) in comparison to the U.S.A. (24,1%). Secondly, immaturity accounts for a high proportion of deaths in the U.S.A. (24-1%) compared with the Netherlands (15’9%). Thus the " mode of delivery " may be the unknown factor causing the difference in perinatal-mortality rate. It has been proposed that aspiration of fresh unclotted maternal blood in amniotic fluid at the time of delivery

may be a major cause of respiratory distress in the newborn infant. And is it not well known that respiratory distress in the newborn is more frequent in cxsarean section,

placenta proevia, and abruptio placenta ? In the U.S.A., where most babies are delivered in hospital, cxsarean sections, episiotomies, and instrumentation are more common, and consequently there is more maternal bleeding and a greater likelihood of aspiration of Department of Health, Education and Welfare, International Comparison of Perinatal and Infant Mortality : The United States and Six West European Countries. Publ. Hlth Serv. Publs, 1000, ser. 3, no. 6, March, 1967. Pender, C. B. Am. J. Obstet. Gynec. 1970, 106, 711.

1. U.S.

2.

778 maternal blood. Many immature infants do not come to necropsy and the cause of death is simply reported as prematurity ". Yet in many of the cases which do come to necropsy the cause of death is found to be atelectasis, even when there has been no clinical suggestion of respiratory distress before death. "

*This work was done in collaboration with Dr. James Zachary, Baltimore City Hospitals haemodialysis unit, and Dr. Vincent Gott, department of surgery, Johns Hopkins Hospital.

Department of Environmental

Medicine, School of Hygiene and Public

Health, Johns Hopkins University, Baltimore, Maryland 21205.

excellent standard of obstetrics, supplePerhaps mented by more care in avoiding blood aspiration, could bring our perinatal mortality down to the levels of our neishbours across the sea. our

Newborn Nursery, Hotel Dieu Hospital, Cornwall, Ontario, Canada.

Sefton General Hospital, Liverpool L15 2HE.

H.

J. GOLDSMITH.

PLASTICISERS FROM P.V.C.

SIR,-Several laboratories, including our own, have demonstrated the presence of phthalate ester plasticisers in blood and acid-citrate-dextrose solutions stored in disposable polyvinyl chloride (P.v.c.) plastic blood packs.1-3 Our own work4 has shown a level of 6 mg. di-2-ethylhexyl phthalate (D.E.H.P.) per 100 ml. of blood stored at 4°C for We have, furthermore, shown the twenty-one days. extraction by blood of plasticisers from P.v.c. plastic laboratory and surgical tubing.5 Our most recent experiments indicate the extraction of two phthalate ester plasticisers by blood from tubing used in the Travenol hxmodialysis and Travenol heart-lung-bypass systems.6** We have lately reported the presence of a phthalate ester plasticiser in the tissues of two patients, of whom one had received a large number of blood-transfusions (13 units) and the other, as well as having had a number of bloodtransfusions, had been on cardiopulmonary bypass for 3 hours.4 Our laboratory is currently investigating the toxicological implications of plasticisers in vivo. In order to assess the effects of plasticisers in man, we can assume that patients on chronic hxmodialysis would be best suited to the evaluation of phthalate esters. To document the presence of plasticisers in such people, we are attempting to obtain tissues from them, either when they come to necropsy or at the time of kidney transplantation. The excellent record of safety of P.v.c. medical devices indicates their general lack of toxicity and the ability of the human organism to dispose of the extracted plasticising materials. However, we reject the contention of Dr. Gesler and Dr. Kartinosthat the margin of safety of D.E.H.P. may be greater than that of water. Since D.E.H.P. is lipophilic, like D.D.T. and the chlorinated biphenyls, its storage in body tissues becomes an important consideration, and thus, more investigations of tissue levels of phthalate ester plasticisers are indicated. 1. 2. 3. 4. 5. 6. 7.

TETRAPLOIDY IN CELLS CULTURED FROM AMNIOTIC FLUID

CHARLES B. PENDER.

ÆTIOLOGY OF MIGRAINE SIR,-I have made the clinical observation that the frequency of attacks in migrainous subjects tends to diminish when an additional long-term disability is acquired -for example, post-herpetic neuralgia or a painful peptic ulcer. Should this observation be borne out by statistical scrutiny, it might lead to a reappraisal of the importance of psychodynamic factors in the astiology of migraine.

Guess, W. L., Jacob, J., Autian, J. Drug Intell. 1967, 1, Marcel, Y. L., Noel, S. P. Lancet, 1970, i, 35. Jaeger, R. J., Rubin, R. J. ibid. July 18, 1970, p. 151. Jaeger, R. J., Rubin, R. J. Science (in the press). Jaeger, R. J., Rubin, R. J. Fedn Proc. 1970, 29, 411. Jaeger, R. J., Rubin, R. J. Unpublished. Gesler, R. M., Kartinos, N. J. Lancet, 1970, i, 1227.

121.

RUDOLPH J. JAEGER ROBERT J. RUBIN.

SIR,-Amniocentesis is a feasible and acceptable procedure for the intrauterine detection of chromosomal abnormalities. Edwards, however, cautioned against its use by laboratories not experienced in the technique. We should like to report the findings, from 2 laboratories, of tetraploidy and tetraploid mosaicism in cells cultured from amniotic fluid. This is particularly pertinent in view of Carr’s finding,2 that women who have been taking oral contraceptives within 6 months of becoming pregnant have a significantly increased frequency of triploid and tetraploid fetuses. A 29-year-old woman, mother of 2 sons with trisomy 21 (47,XY,21 +), underwent amniocentesis during the 4th month of her third pregnancy. Chromosome analysis performed after the amniotic cells had been in culture 42 days revealed only tetraploid cells (30 metaphases examined). The pregnancy was allowed to go to term, and the mother delivered a normal female infant. Peripheral-blood cultures performed on the infant shortly after delivery, and on both parents, revealed normal chromosomes and showed no evidence of significant polyploidy. A 14-year-old girl underwent amniocentesis during the 26th-30th week of gestation because of suspected fetal malformation. Chromosome analysis of amniotic cells after 20 days in culture revealed 4 out of 30 (13%) tetraploid metaphases. The diploid cells had a normal male karyotype. A second chromosome analysis performed on this same culture 2 weeks later-i.e. after 35 days in culture-revealed no tetraploid cells. After 9 months’ gestation, the mother delivered a healthy male infant. Chromosome analysis on the baby shortly after delivery revealed normal chromosomes and no evidence of tetraploidy. A 28-year-old woman, whose first child, a boy, had trisomy 21 (46,XY,21 +), underwent amniocentesis during the 4th month of gestation. Chromosome analysis of the amniotic cells after 14 days in culture revealed 111out of 200 (56%) tetraploid metaphases (92,XXYY). Amniocentesis was repeated 3; weeks later, and chromosome analysis after 11 days in culture again revealed 21 out of 40 (50%) tetraploid metaphases. On the basis of these findings the pregnancy was terminated. The aborted fetus appeared normal. Chromosome analysis of fetal skin-cultures revealed 3 out of 100 tetraploid cells, and cord-blood showed 2 out of 668 tetraploid cells. Karyotypes of both parents were normal. We feel that the finding of a significant number of tetraploid cells in amniotic-fluid cultures presents a diagnostic dilemma. Is this a normal (though uncommon) phenomenon of amniotic-cell cultures, or should such laboratory results constitute an indication for pregnancy termination ? The fact that in our third case cultures from two separate amniocenteses revealed similar degrees of tetraploidy makes a laboratory artefact unlikely. In addition, since the karyotype was these could not have been maternally derived cells.

male,

1. 2.

Edwards, J. H. Lancet, 1970, i, 608. Carr, D. H. Med. Clins N. Am. 1969, 53,

1039.