924 et al. Polycythxmic diseases caused conditions at sea level and limited acclimatisaby pathological tion at high altitude may thus be useful comparative models.

that

reported by Thomas

Biophysical Laboratory, Universidad Peruana Cayetano Heredia, P.O. Box 5045, Lima, Peru

J. WHITTEMBURY C. MONGE

COMMUNITY EXPOSURE TO ASBESTOS

S!R,—You state that people living near an asbestos mill in Yorkshire have acquired asbestosis, but the reference you cite22 does not give a source for this information. Your view has been copied into the New England Journal of Medicine,3so it is

acquiring credibility by repetition. Is your statement correct? I suspect that this depends on how asbestosis is defined. Many texts are vague as to which asbestos-induced diseases are included in the term. The official guide to the Industrial Injuries Act4 states that the disease takes one of two forms-the first producing alveolar fibrosis and the second pleural thickening. However, few physicians would include isolated pleural disease as asbestosis but would accept Parkes’s’ definition of fibrosis of the lungs caused by asbestos dust. Community exposure may cause parietal pleural plaques,6 but it is doubtful if these ever produce disability, even when extensive. Relatively light exposure may also produce pleural effusions which sometimes result in considerable thickening of

both pleural layers and restrictive impairment of ventilation. As far as I know these pleural diseases have no other significance, except as markers of asbestos exposure. From what I have been told asbestos was dispersed over a wide area around the mill, and local people unconnected with the industry have acquired pleural plaques and effusions. It does not sound as if there was sufficient asbestos dust pollution to produce alveolar fibrosis and I have seen no evidence to date that this has happened. Department of Thoracic Medicine, City Hospital, Nottingham NG5 1PD

and Greenberg and Davies10 have recorded cases of community exposure in which mesothelioma subsequently developed. Bohlig and Hain" have investigated mesothelioma in the residential area close to the Hamburg shipyard with its high asbestos content, and Wagner and colleagues12 have described patients living in the vicinity of asbestos who have subsequently had mesotheliomas. Death due to mesothelioma presumably is preceded by disability caused by pleural asbestosis, and mesothelioma has certainly been recorded after community exposure. With a long-term (40 year) disease like pleural asbestosis great caution should be exercised before it is dismissed as harmless. Halifax Infirmary, Halifax HX1 2YP

Royal

RESPIRATORY DISTRESS IN NEWBORN

SIR,-Dr Brice and Dr Walker (Oct. 8, p. 752) suggest that

improved diagnostic criteria are needed for respiratory distress in the newborn before comparisons of incidence and mortality may be made between different centres. We suggest that such a diagnostic test exists in the lecithin/sphingomyelin (L/S) ratio of the hypopharyngeal aspirate or gastric aspirate of newborn infants.’ This ratio differentiates clearly between groups of infants, in whom the diagnosis is not in doubt, with transient tachypnoea and those with hyaline-membrane disease. We now use this method to clarify the diagnosis of infants with respiratory distress of uncertain cause. MORTALITY, BIRTH-WEIGHT, AND GESTATION FOR INFANTS IN RELATION TO NEONATAL

**We

following

comments on

this problem.-ED.L.

SIR,-Dr Davies is

correct to state that the argument the definition of asbestosis. Is asbestosis exclusively a disease of the lung parenchyma or can the pleura also be damaged by asbestos fibres? Some of my patients have pleural asbestosis due to community exposure, and I shall be discussing this issue in a Milroy lecture to be delivered at the Royal college of Physicians on March 16, 1978. Dr Davies is on dangerous ground when he says that it is doubtful if pleural asbestosis ever produces disability. Harries et al. state that there is "some evidence to suggest that pleural abnormalities are associated with changes in lung function". Jodoin et awl. have described twenty-four asbestos workers who had normal chest radiographs but who were found to have restrictive lung disease. Furthermore, Newhouse and Thompson9

hinges

L/S RATIO

D. DAVIES i

thank Dr B. T. Mann for the

BERTRAM T. MANN

on

1. Lancet, 1977, i, 1115. 2. ibid. p. 944. 3. New England Journal of Medicine, 1976, 295, 490. 4. Pneumoconiosis and Allied Occupational Chest Diseases. H.M.

Stationery Office, 1967. 5. Parkes, W. R. Occupational Lung Disorders. London, 1974. 6. Meurman, L. Envir. Res. 1968, 2, 30. 7. Harries, P. G., Mackenzie, F. A., Sheers, G., Kemp, T. P. Br. J. ind. Med. 1972, 20, 277. 8. Jodoin, G., and others Am. Rev. resp. Dis. 1971, 104, 525. 9. Newhouse, M. L., Thompson, H. Br. J. ind. Med. 1965, 22, 264, 266.

I

I

From Jan. 1, 1975, to Dec. 31, 1976, 964 infants born in the John Radcliffe Hospital, Oxford, were admitted to the special-care baby unit. 118 of these infants were judged, by standard criteriato have probable hyaline-membrane disease. The neonatal mortality in the total group was 27%. Pharyngeal L/S ratios from the hypopharyngeal aspirate were obtained soon after birth in 68 (57%) of these infants. 45 (66%) of L/S ratio measurements in this group indicated immaturity (L/S 1.8or less). The remaining 23 L/S ratios were greater than 1.8. The clinical details and neonatal mortality in these groups are shown in the table. The neonatal mortality of infants showing symptoms of hyaline-membrane disease with an immature L/S ratio was significantly higher than that in infants with signs of respiratory distress but with a mature L/S ratio. The 2 deaths in infants with a mature L/S ratio were from intraventricular haemorrhage at an early age. Their birth-weights were 1000 and 1055 g. All deaths in the group with L/S ratios 1-8 were due to respiratory causes or intraventricular haemorrhage. Hyaline-membrane disease is thought to be due to insufficient free lung surfactant. The measurement, in the immediate neonatal period, of a variable such as the pharyngeal or gas10. Greenberg, M., Davies, A. ibid. 1974, 31, 96. 11. Bohlig, H., Hain, E. Biological Effects of Asbestos; p. 217. W.H.O., Geneva, 1972. 12. Wagner, J. C., Sleggs, C. A., Marchand, P. Br. J. ind. Med. 1960, 17, 269. 1. Weller, P. H., Jenkins, P. A., Gupta, J., Baum, J. D. Lancet, 1976, i, 12. 2. Davies, P. A., Robinson, R. J., Scopes, J. W., Tizard, J. P. M., Wigglesworth, J. S. Medical Care of Newborn Babies. Spastics International Medical Publications, London, 1972.

925 tric L/S ratio, which is related to surfactant levels, is more likely to define infants with hyaline-membrane disease than are tests of lung function or clinical data, and should be made when comparisons of mortality from the disease are drawn. R. W. I. COOKE P. JENKINS Department of Pædiatrics, P. HOWAT Radcliffe Hospital, John Headington, Oxford OX3 9DU

J. D. BAUM

IS GARDNER SYNDROME A DISTINCT GENETIC DISORDER?

SIR,-In the autosomal dominant adenomatoses of the rectum (A.C.R., familial polyposis coli) the colonic polyps invariably become malignant. Gardner’ described such a family (no. 109) who also had extracolonic benign growths (fibromas, sebaceous and epidermal inclusion cysts, osteomas)2 which showed pleiotropism. Since then clinical features and family histories have raised the question-is Gardner syndrome a distinct genetic entity? As part of the National Large Bowel Cancer Project 17 families with A.C.R., including family 109, were studied with respect to detailed family pedigrees, clinical phenotypes of all family members, and cell culture of skin obtained from family members and members by marriage willing to participate. In 7 families the clinical phenotype was solely colonic polyps with adenocarcinoma of the colon or with a family history of colonic cancer (see table). In the other 10 families, some or all of the extracolonic growths associated with the Gardner syn-

colon and

noted in the original pedigree of family in the part of the family group in which the syndrome was expressed. Skin cancer was an extracolonic feature in 6 of the 10 families we studied-either in an affected member in the family (3 with basal-cell carcinoma and 1 with melanoma) or as part of the family history (2 families). There was increased tetraploidy in cultures established from skin taken from affected individuals in A.C.R. families with extracolonic lesions, but not from skin from families without extracolonic lesions.’ The addition of skin cancer to the extracolonic lesions and the finding of increased in-vitro tetraploidy in skin cultures are further evidence that the Gardner syndrome forms a distinct group within A.C.R. This study illustrates the advantages of using different disciplines (genetic fieldwork, clinical evaluation, and in-vitro tests) to elucidate a genetic syndrome. Skin

cancer was

1093 but

not

This investigation was supported by Public Health Service grant CA-15973-04 from the National Cancer Institute through the National Large Bowel Cancer Project.

Laboratory for Cell Genetics, Department of Medicine, Cornell University Medical College, New York, N.Y. 10021, U.S.A.

B. SHANNON DANES

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland

ANNE J. KRUSH

Department of Biology, Utah State University, Logan, Utah

ELDON J. GARDNER

drome were present.

TOPICAL STEROIDS Dr Majumdar (Oct. 8, p. 758) does not of the side-effects associated with the use of fluorinated corticosteroids. The evidence now available suggests that these side-effects result entirely from the inability of the steroid to be metabolised locally in the skin, thereby creating a cumulative depot effect, the rate of application to the skin being much greater than the rate of disappearance. For a steroid to remain susceptible to local metabolic degradation by epidermal oxidases, the 17-hydroxyl group must remain free. Any 17 ester, therefore, is resistant to this oxidation, whether or not it contains fluorine, and it is significant that all topical synthetic corticosteroids with increased antiinflammatory activity contain 17 esters. Expressing the problem in terms of the fluorine only disguises the real cause of the

SIR,-Your reply

1. Gardner, E. J. Am. J. hum. Genet. 2. Gardner, E. J. ibid. 1962, 14, 376.

1951, 3, 167.

CLINICAL PHENOTYPES AND INCREASED IN-VITRO TETRAPLOIDY IN 17 FAMILIES WITH A.C.R. (FAMILIAL POLYPOSIS COLI)

fully explain

the

side-effects. The situation is sone

to

cause

entirely

different with natural

which, having a free 17-hydroxyl group,

soon

hydrocortidegrades in

the skin. The explanation may be confirmed by carrying out the vasoconstrictor assay on steroid creams and reoccluding 2-3 weeks after application. All steroids with 17 esters which result in initial blanching will reproduce that blanching, whereas steroids without the 17 ester will not. Admittedly any steroid, including hydrocortisone, will produce side-effects if used in large amounts over long periods and especially under polyethylene, but these cases represent only a small fraction of the whole. Dermal Laboratories,

Gosmore, near Hitchin, Herts SG4 7QR

p.

MARTIN WHITEFIELD

SIR,-Your excellent editorial and Dr Marks’ letter (Oct. 8, 758) prompt me to send the following "10+1 command-

ments" : *

Excluding jaw lesions.

t Based

number of metaphases showing tetraploidy divided by the total number of metaphases counted on slides having at least 50 divisions per slide.2 Preventive colectomies. S Family 109. on

(1) Topical corticosteroids are still the most effective external remetherapy but you must assess their use critically. Also l,ote

dies for skin

J., Woolf, C. M., Shaffer, J. O. Proc. 2nd 1952, 1, 846. Danes, B. S. J. med. Genet. 1976, 13, 52.

3. Gardner, E. 4.

natn.

Cancer

Conf.