HUMAN PLACENTAL LACTOGEN IN LATE PREGNANCY

105 of Northumbrian bagpipes, which also use bellows, but have a different fingering from Scottish pipes, might be able to help. It is also possible for a handyman, which some doctors and pipers are, to make a set of bellows-pipes using a half-size Highland bagpipe chanter and drones-which should be readily obtainable from a Scottish (or, more cheaply, a Pakistani) bagpipe maker. Department of International Community Health, Liverpool School of Tropical Medicine, Liverpool L3 5QA

DAVID STEVENSON

EARLY DIAGNOSIS OF DUCHENNE MUSCULAR DYSTROPHY cases of Duchenne muscular in families where a son with D.M.D. has been born, Dr Gardner-Medwin and his colleagues (May 20, p. 1102) suggest screening for increases in serum-creatinekinase (c.K.) in boys who are unable to walk at 18 months of age. They estimate that 8.2% of 122 D.M.D. births in NorthEast England between 1952 and 1967 might have been prevented by c.K. screening of boys at 18 months, while the births of 13. 1% of these D.M.D. boys could have been prevented if the disease had been diagnosed neonatally in an older brother. The reasons Gardner-Medwin et al. gave for screeening at 18 months instead of immediately after birth are the lower number of screening tests required (9000 for the U.K.), easier interpretation of abnormal results, and, for 18 months, avoidance of distress in affected families. Our pilot c.K. screening programme on 16 500 newborn (both sexes) in 1975 in South-West Germany,1 during which 5 boys with preclinical D.M.D. were found, showed that neonatal c.K. screening might prevent further D.M.D. births in affected families: Case .—First child, male, born April 1, 1975; picked up on April 5 by C.K. screening. On June 24, 1975, conventional serum enzyme

SIR,-To prevent secondary

dystrophy (D.M.D.)

analyses2 showed abnormal results (c.K. 3636 U/l, adolase 15 U/1). (Normal ranges for C.K. 0-50 adults, 0-80 children 3 weeks to 1 year; for aldolase 0.9-2.5.2) The electromyogram (E.M.G.) gave a pathological pattern. The mother, age 25, could not be identified as a D.M.D. carrier (C.K. 17 UII, aldolase 1.5U/1, normal E.M.G.). On Dec. 7, 1976, the second son was born (conceived when the first son was about 11l months old). In November, 1977, he was admitted to our hospital for recurrent enteritis and hepatosplenomegaly, but was subsequently found to have preclinical D.M.D. as well (c.K. 6480 U/l, aldolase 67 U/1). Histochemistry (light microscopy) and electronmicroscopy on muscle tissue obtained by biopsy from the left triceps and the left quadriceps of both children revealed a degenerative myopathy typical

of early D.M.D. Case 2.-Third child, male, born March 13, 1975, was found positive on C.K. screening (March 18). On May 27, conventional enzyme tests (C.K. 1650 U/1, aldolase 37 U/1) and E.M.G. were abnormal. The 2-year-old sister, born Oct. 20, 1972 (C.K. 1350 U/1, aldolase 29 U/1, pathological E.M.G.) and the 24-year-old mother (c.K. 129 U/1, aldolase 4-4 U/1, pathological E.M.G.) were D.M.D. carriers. The 6-year-old first son was

healthy.

These two examples show that c.K. screening at birth can, as Gardner-Medwin et al. suggest, prevent secondary D.M.D. births, even in families where the mother cannot be identified as carrier-provided the early diagnosis is followed by effective genetic counselling.3 Unfortunately, the parents did not follow our advice. Early detection of D.M.D. carriers is even more important for preventing D.M.D. Case 2 could have been prevented if his sister had been identified as carrier before his conception (about June, 1974), when she was 20 months old. c.K. activities in young carrier girls can be quite high. Our own data and those of others4 indicate that, as a consequence of lyonisation, the 1. Beckmann, R.,

Scheuerbrandt, G. Kinderarzt, 1976, 7, 1267; Beckmann, R., Scheuerbrandt, G , Antonik, A. Mschr. Kinderheilk. 1976, 124, 658.

values of carrier girls decrease with age until, in many they reach the normal range at adulthood; in the first months of life, they seem to increase, as do c.K. values in c.K.

cases,

D.M.D. boys. Screening,

D.M.D. boys and D.M.D. carrier girls, in period can prevent 25-30% of all D.M.D. male births-namely, those born in families where an earlier child is either a D.M.D. boy or a carrier girl. If the detected carriers

both for

the neonatal

later do not have children of their own, D.M.D. should decrease to the level of spontaneous cases. When we apply GardnerMedwin’s data to West Germany we find that, of the 125 D.M.D. boys born each year, 30-38 might be prevented quite soon after the start of a general c.K. screening programme, and we could predict that the incidence of D.M.D. would fall to about 40 per year after one generation. In our opinion, preventing 85 D.M.D. boys per year warrants a general screening programme for all newborns (about 600 000 per year) in West Germany, especially if one applies a figure of approximately DM 500 000 as total cost to society of one D.M.D. boy. We have started a voluntary c.K. screening programme in West Germany, where boys and girls are tested at 4-6 weeks of age. The voluntary nature of this programme ensures that only families participate who are ready to accept the positive and negative consequences of early diagnosis. Department of Pædiatric Muscle Disease, Universitätskinderklinik, D-7800 Freiburg, Germany

ROBERT BECKMANN MANFRED SAUER

Department of Electronmicroscopy/ Histochemistry, Max Planck Institut für Immunbiologie,

Freiburg

UWE-PETER KETELSEN

CK-Test-Laboratorium, D-7821 Breitnau bei Freiburg

GUNTER SCHEUERBRANDT

HUMAN PLACENTAL LACTOGEN IN LATE

PREGNANCY

SIR,-Dr Bradford and Dr Hargreaves1 report a normal pregnancy with low serum H.P.L. (human placental lactogen). altered immunological properties of the H.P.L. defect in production, and/or abnormally rapid destruction ofH.p.L. as explanations for this. We have seen a case with very low H.P.L. values.2 A 27-yearold primigravida had serum-H.p.L. values of 0.4. 0.7, and 0-6 mg/1 at weeks 38, 39, and 40, respectively. The pregnancy was otherwise uneventful and a normal male infant weighing 3740 g was delivered at term. The placenta, weighing 620 g, was both macroscopically and microscopically normal, and examination by electronmicroscopy revealed no differences compared with normal-term placentae. Concentrations of human chorionic gonadotrophin (H.C.G.), progesterone, SP prolactin, glucose, and total oestriol in maternal serum were measured in 38th, 39th, and 40th weeks of pregnancy. Prolactin and H.C.G. concentrations were greatly increased (2700 p.g/1 and 110 000 t.u./1, respectively), while the other serum concentrations were normal. In the umbilical artery and vein blood H.P.L. was undetectable (<0.001 mg/1), and in the intervillous spaces the concentration was only 0-9 mg/1, which is about 1/25th of normal. This indicates a defect in the production of H.P.L. in placenta, but since H.P.L. concenwere measured by immunological methods trations (immunoassay kit, Radiochemical Centre, Amersham, and immunoelectrophoresis’) the possibility of altered immunological properties of the H.P.L. molecule is still open. Cases of very low H.P.L. concentrations in normal pregnancies are rare. Over the past six years we have done serum-

They suggest molecule,

a

2. Deutsche Gesellschaft für klinische Chemie Z. klin. Chem. klin. Biochem.

1970, 8, 658, ibid. 1971, 9, 464; ibid. 1972, 10, 182. Emery, A. E. H., Watt, M. S., Clack, E. R. Clin. Genet. 1972, 3, 147. 4. Moser, H. Schweiz. Rundschau Med. (Praxis), 1977, 66, 814. 3.

1. Bradford, W. P., Hargreaves, T. Lancet, 1973, i, 1213. 2. Gaede, P., Trolle, D., Pedersen, H. Acta obstet. gynæc. scand. 1978, 57, 203. 3. Nørgaard-Pedersen, B., Gaede, P. Scand. J. Immun. 1973, suppl. 1, p. 129.

106

analyses routinely

H.P.L.

women, but

we

on

more

have found only the

than 20 000 pregnant of very low H.P.L.

one case

of Obstetrics and Clinical Chemistry,

Departments

Rigshospitalet, Copenhagen, Denmark and Department of Obstetrics, Herlev Hospital, Copenhagen

ELEVATED METABOLIC RATES IN OBESITY

SiR,—Ihave no objections to the major conclusions drawn by James et al.1 in their paper on metabolic rates in obesity, but I

DYRE TROLLE PREBEN GAEDE HENNING PEDERSEN

SATIETY VALUE OF WHOLEMEAL AND WHITE BREAD

SIR,-Haber et at.’ found that the refined product of a carbohydrate food source (apple) was less satisfying to the appetite than the original. We have done similar studies with bread. Twelve healthy volunteers were asked to eat bread to a point of comfortable fullness. In randomised sequence they wholemeal and white bread. The results are shown in the Ten of the twelve ate more white bread than wholemeal, and the difference was statistically significant (Wilcoxon matched-pairs signed-ranks test, t=14, P<0.05). This supports the notion2,3 that refinement of carbohydrate results in an increased intake of energy. In addition to the increased weight of white bread eaten it must be remembered that white bread has a greater energy density than wholemeal bread, 2. 3z, compared with 2.16 calories /g.4 ate

figure.

concerned that some readers may be misled by some in their discussion. For example, they state that the expression of metabolic rate in terms of either surface area or "metabolic body size" may be unhelpful in identifying changes in energy intake or expenditure during the development of obesity. However, in reviewing their data, it would seem that the resting metabolic rates (R.M.R.S) of their subjects were responding to changes in body-weight in a predictable manner based on well-established empirical estimates of metabolic rate based on metabolic body size.2 In the figure I have plotted the theoretical metabolic rates for six "typical" men or women (obese or normal) using the anthropometric indices of the obese or normal subjects referred to in their article. The equations which were used are given in the legend to the figure. The calculations of the six data points for either men or women are based on the average values for the weight (w) and height (h) of their subjects or the average values ±11 S.D. Since James et al. found height to be significantly correlated with the R.M.R., the calculation of h/wl/3 (specific stature, see legend to figure) was obtained using (average h)/(average W)I/3, (average h + s.D.)/(average w + S.D.)l/3 or (average h - s.D.)/(average w - s.n.)’3, and so on, to simulate indices which were typical of those of their patients. Furthermore, since the values for height (obese versus normal) were essentially identical with S.D.S of the same inagnitude, it was also possible to calculate a metabolic rate minus an "expected" metabolic rate of a normal subject of the same am

comments

1.

James, W. P. T., Davies,

i, 1122. 2. Klieber, M. The Fire New York, 1961.

Satiety points

for

consumption of wholemeal

of Life:

L., Bailes, J., Dauncey, P. L. D. Lancet, 1978, an

Introduction

to

Animal

Energetics; p. 177.

and white bread.

different occasion5 we looked at the hormone response meals of equal weights of wholemeal and white bread; again paired tests performed in randomised sequence in healthy volunteers. We measured blood sugar, insulin and glucagon responses, looking at maximum values, maximum increase, time to maximum value and integrated response. In no respect was there a significant difference between the test meals. Nor was there any correlation with the rates at which these test meals left the stomach. It is possible that refinement of carbohydrate to the point of solubility in water in necessary to induce the hyperinsulinsemia reported by Haber et aU On

H.

a

to test

Royal Infirmary, Blackburn, Lancashire BB2 3LR

D. S. GRIMES

Manchester Royal

C. GORDON

Infirmary

ii. 679. 2. 3. 4.

Cleave, T. L. The Saccharine Disease, Bristol, 1974. Heaton, K. W. Lancet, 1973, ii, 1418. Southgate, D. A. T., Paul McCance and Widdowson Composition of Foods.

5.

Grimes, D. S., Goddard, J. Gut, 1977, 18, 1725.

Stationery Office, 1978.

body-weight.

The equation used for men was metabolic rate = 72.1 x w3/4 x (1 + 0.004 [30-a] + 0.01 [s-43.3]), and the equation used for women was metabolic rate 65.8 x W3/4 x (1 + 0.004 [30-a] + 0.018 [s-43.4]), with w weight (kg), a = age, and s height (cm)/wIl3. A value of 43 years was used for age. For the small inserted figure the desirable weight range was taken to be equal to 66.8±8 kg (men) or 5-57+6-8 kg (women) for heights of 176+7 (men) or 162+6 (women), respectively. The data points in the small inserted figure represent the R.M.R. for a "typical" obese subject minus the R.M.R. for a corresponding "typical" normal subject of the same height. It was assumed that the R.M.R. would be approximately equal to and/or a function of the basal metabolic rate. The above equations are usually used for basalmetabolic-rate calculations.I =

=

1. Haber, G. B., Heaton, K. W., Murphy, D., Burroughs, L. F. Lancet, 1977,

H.M.

Relation between estimated R.M.R. and

=