SPHERICAL ALVEOLI AND SUDDEN INFANT LUNG COLLAPSE SYNDROME

217

pointed out that this subtype is associated with excess winter births, and state "the brain damage effect of cold months’ births has more serious long-term sequelae [ie, development of paranoid schizophrenia] in males". This is a view not dissimilar to our own

hypothesis. There are many parallels between the genetics of schizophrenia, and of other common disorders such as diabetes or coronary heart disease. The latter is a-useful model.5 Monogenic familial hypercholesterolaemia predisposes to early coronary artery disease. Although most people with coronary disease do not have this abnormal gene, the clinical features of this highly familial form and the more common varieties are indistinguishable. Smoking, diet and other environmental factors are of major importance in the aetiology of the common form, but even among those with the abnormal gene individuals who smoke or become obese are at higher risk than the gene carriers who avoid these risk factors. Similarly, the offspring of schizophrenic parents who also have perinatal complications are at greater risk of later schizophrenia than those with a normal birth. The fact that coronary artery disease is frequently non-familial and overwhelmingly environmental in aetiology does not exclude the probability that "normal" individuals vary in their susceptibility to smoking and overeating. Likewise, allelic variation within the normal range may render individuals more or less susceptible to the environmental factors implicated in sporadic schizophrenia. Thus, the difference that we propose between the familial and sporadic groups lies in the relative importance of genes and environment. It can only be relative because environmental effects interact with familial predisposition, and because the familial/sporadic distinction is as yet imprecise and contaminated by false positives and negatives. Our sporadic group will contain individuals in whom the schizophrenia is clearly secondary to some environmental agent where there may be an obvious cerebral lesion. It will also contain individuals in whom any evidence of causation (environmental or genetic) is lacking at present. We advocate a separation on the basis of family history as a first step to allow delineation of groups in which aetiological heterogeneity is reduced, and believe that it will be useful to pay particular attention to those cases where genetic and environmental factors are most distinct. The intensive study of familial hypercholesterolaemia has been most productive, but no one would suggest that the existence of this familial type of coronary artery disease is a sensible reason for ignoring the important environmental risk factors in heart disease. DeLisi et al suggest that our proposed methodology is inherently weak. Their strategy, as they report it, fails to discriminate between the major influences, genetic and environmental, on the development of schizophrenia.

Institute of Psychiatry, London SE5 8AF

A. M. REVELEY S. W. LEWIS R. M. MURRAY

numbers, it seems unlikely that we are simply making a type II error, and, as Dr DeLisi and colleagues point out (June 29, p 1502), other studies are in agreement with ours. Previous studies have used as a cut-off value for VBR to define ventricular enlargement a control-group mean plus two standard deviations.l-3 The resulting cut-off has varied considerably between studies (6% to 62% of subjects being defined as showing enlargement); nor is it clear whether adopting such a cut-off is valid. The range of VBRs for schizophrenic patients in most studies is continuously distributed with no clear division into subgroups. In their use of control group comparisons Reveley and Chitkara appear to be bending over backwards to find a way to support an earlier twin finding when, on their own admission, there is no significant difference in ventricular size between family history positive and negative subjects. A real association between family history and ventricular size should be a consistent and replicable finding across studies, and this is clearly not so at present. We are puzzled by Reveley and Chitkara’s use of "family history for major psychiatric disorder" for their family history positive group. Most modern studies on the genetics of schizophrenia suggest that what is inherited is a liability to schizophrenic illness and/or a tendency to personality deviation of schizoid or "schizophrenia spectrum" type rather than a general vulnerability to psychiatric disorder. What proportion of a non-psychiatric population would be "family history positive" by Reveley and Chitkara’s criteria is unknown. If the lifetime prevalence of major psychiatric disorder is about 10% (according to recent American population prevalence studies this is a conservative figure4), then by chance alone a member of the general population with five relatives has a 41 % probability of having a relative with such a disorder. How many of Reveley and Chitkara’s control group were "family history

positive"? ANNE FARMER PETER MCGUFFIN

Institute of Psychiatry, London SE5 8AF

Graylingwell Hospital, Chichester, West Sussex

ROBERT JACKSON

Springfield and St George’s Hospitals,

PETER STOREY

London SW17

1. Andreasen NC, Smith MR,

enlargement

in

Jacoby CG, Dennert JW, Olsen SA. Ventricular schizophrenia: Definition and prevalence. Am J Psychiatry 1982;

139: 292-96.

SA, Jacobs L, Kinkel WR. Changes in size of normal lateral ventricles during by computerized tomography. Neurology 1976; 26: 1011-13. Weinberger DR, Torrey EF, Neophytides AN, Wyatt RJ. Lateral cerebral ventricular enlargement in chronic schizophrenia. Arch Gen Psychiatry 1979; 36: 735-39. Robins LN, Helzer JE, Weissman MM, et al. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 1984; 41: 949-59.

2. Barron

aging determined

3. 4.

SPHERICAL ALVEOLI AND SUDDEN INFANT LUNG COLLAPSE SYNDROME

SIR,-While lending experimental support 1 2 3

4 5.

Schulsinger F, Parnas J, Petersen ET, et al. Cerebral ventricular size in the offspring of schizophrenic mothers. Arch Gen Psychiatry 1984; 41: 602-06. Owens DGC, Johnstone EC, Crow TJ, et al. Lateral ventricular size in schizophrenia. Psychol Med 1985; 15: 27-41. Nasrallah HA, Kuperman S, Hamra BJ, McCalley-Whitters M. Clinical differences between schizophrenic patients with and without large ventricles. J Clin Psychiatry 1983; 44: 407-09. Nasrallah HA, McCalley-Whitters M. Seasonality of birth in sub-types of chronic schizophrenia. Acta Psychiatr Scand 1984; 69: 292-95. Motulsky AG. Genetic research in coronary heart disease. In: genetic epidemiology of coronary heart disease: Past, present and future. New York: Alan R Liss, 1984: 541-43.

SIR,-Dr M. Reveley and Bina Chitkara (June 29, p 1503) report results in singleton schizophrenics which, they say, support twin study findings of an environmental effect causing cerebral ventricular enlargement in subjects with negative family history for "major psychiatric disorder". They suggest that our failure (June 8, p 1333) to find such an effect is due to a type II error and the absence of control group data. Our subjects with a positive family history of schizophrenia had the larger mean ventricle-brain ratio (VBR), a finding which is the opposite direction to that of Reveley et al. Thus, despite small

to

the alveolar

instability component of our hypothesis,’ Morley et al2 show a healthy scepticism for the spherical mathematical model on which it is based. The model was derived from animal studies.3,4 Gil et al3 illustrated pleating into the corners of septal wall junctions in normal lungs. In the presence of a finite surface tension the suction under the surface of the aqueous layer at the corners is higher than under flatter walls because of the smaller radius of curvature at the corners. This draws any surplus fluid and any slack in the alveolar wall into the corners, filling them out and increasing the radius of the curvature of the air-fluid surface which is of course the component that generates the need for a supporting pressure. The result reported by Gil et al3 at 80% total lung capacity (TLC) is a good approximation to spherical bubbles. Our figure (upper part) shows this capacity schematically. Gil et al found that, at lower volumes, the shape became more irregular, as might be expected with compression of the surfactant film and consequent reduction of surface tension. Bachofen et a14 removed much of this surfactant effect by rinsing the lungs with a detergent, which resulted in a surface tension of around 20 dynes/cm, the value measured in cases of sudden infant death syndrome (SIDS) by Morley et al. Widespread local alveolar

218

collapse, as an important component of prolonged expiratory apnoea and the sudden infant lung collapse syndrome hypothesis. In our opinion, in the surfactant-defective lung, the sphere or tube represent valid models for the shape of the air/fluid interfaces which generate the local pressures and require support from surrounding lung tissues. alveolar

Cardiothoracic Institute, University of London, London SW36HP

D. G. TALBERT DAVID SOUTHALL

DG, Southall DP. A bimodal form of alveolar behaviour induced by a defect in lung surfactant—a possible mechanism for sudden infant death syndrome. Lancet

1. Talbert

1985; i: 727-28. 2.

Morley CJ,

Davies

RJ,

Hill

CJ, Heath ME. Alveoli and abnormal surfactant. Lancet

1985; i: 1330. 3. Gil J, Bachofen H, Gehr P, Weibel ER. Alveolar volume-surface area relation in air-

4.

5. 6.

7. 8.

Representations of cross-section of lung. Upper: cross-section of lung tissue possessing

defective surfactant at high volume. Lower: lung tissue (from above) after collapse at low lung volume. Many alveoli are crumpled and their remaining internal space is filled with fluid at low pressure. Those remaining open are distended, as are airways. Output from stretch receptors has increased as result of collapse.

collapse was observed, but they comment "the wide air spaces have a conspicuously spherical shape even at low lung volume". A figure in their report demonstrates that at 40% TLC the presence of this increase in surface tension squashes capillaries and macrophages to conform to a spherical outline. Their figure also demonstrated the large suction which this surface would produce, possibly resulting in an influx of fluid from pulmonary capillaries through pores present in the alveolar epithelium. (Type II cells normally maintain a sodium osmotic gradient across these pores which is thought to be an important aspect of surfactant subphase control .5 ) A change in surfactant subphase induced by flooding will probably further modify surfactant performance. Pulmonary oedema is frequently reported at necropsy in SIDS victims. Ifa change in the subphase is an important component of a surfactant defect and is restored post mortem as vascular pressures are removed, this could provide one possible explanation for the negative findings of Fagan and Milner7 in the pressure/volume characteristics of lungs from SIDS cases. Should flooding begin the radius of the fluid surface decreases, the suction increases, and all air may be expelled The pressure in the contained fluid then depends on the radius of the nearest air interface. This may be the mouth of the alveolus, which must be smaller than the alveolus itself, and so pressure remains reduced. Collapsed regions in which alveolar walls have been drawn in and crumpled to fill the space are shown in our figure (lower part), based on the report of Bachofen et a1.4 The supporting tissue forces mentioned by Morley et al were intended to be represented in the shape of the MinT =curve of figure B in our paper.1Alveolar walls cannot support compressive forces but are held in mild tension by attachment to their neighbours by connective tissues which run through them, and eventually to more rigid structures such as airways. The tensions set up in this network by widespread collapse would lead to dilatation of these airways, as was observed by Bachofen et a1.4 As reviewed by Widdicombe,8stretch receptors are located in airways, not in the alveoli, and we drew attention to the possibility of stretch receptors signalling an increase in the lung volume, when in fact there was

and saline-filled lungs fixed by vascular perfusion. JAppl Physiol: Respir Envir Exercise Physiol 1979; 47: 990-1001. Bachofen H, Gehr P, Weibel ER. Alterations of mechanical properties and morphology in excised rabbit lungs rinsed with a detergent. J Appl Physiol: Respir Envir Exercise Physiol 1979; 47: 1002-10. Crandall ED. Fluid balance across alveolar epithelum. Am Rev Resp Dis 1983; 127 (suppl): S1-S65. Krous HF. Sudden infant death syndrome: Pathology and pathophysiology Pathol Ann 1984; 19: 1-14. Fagan DG, Milner AD. Pressure volume characteristics of the lungs in sudden infant death syndrome. Arch Dis Child 1985, 60: 471-85. Widdicombe JG. Pulmonary and respiratory tract receptors. J Exp Biol 1982, 100:

METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

SIR,-We would like to add some points to those raised by Dr Bradley and co-workers (June 29, p 1493) regarding the epidemiology and control of methicillin-resistant Staphylococcus aureus (MRSA). We have experienced problems with similar strains of MRSA, some of which have a plasmid conferring chloramphenicol resistance and the cryptic plasmid alluded to by Bradley et al. We controlled our first outbreak, in the intensive therapy unit (ITU) and a urological ward last year, but further outbreaks have followed the reintroduction of similar strains by patients transferred,from other hospitals. We are trying to control this by screening inter-hospital transfers, and the hospital computer system has been used to identify previous and current carriers when they are readmitted.’ This is difficult, costly, and labour intensive. Recently an MRSA strain was introduced by an agency nurse, who had cared for a carrier in a cardiothoracic unit of another hospital over the previous two days. It is difficult to staff hospitals, and ITUs especially without agency nurses; our current policy is that agency nurses should not work in our wards where there are patients with MRSA. We also try to ask all agency nurses whether, in other hospitals, they have attended patients with MRSA, and we inspect them for cuts and lesions and take a swab where appropriate. Staff with infected lesions, eczema, or dermatitis should not be allowed to work. Staff with clean cuts or abrasions are asked to apply chlorhexidine and alcohol (’Hibisol’) before and after patient contact. We screen agency nurses after they have worked in an affected ward and on occasions provide a decontaminant, but it may be more practicable for hospitals to offer all nurses disinfectants to decontaminate themselves before working in other hospitals. This issue needs discussion at a national level. A similar approach may be necessary with locum or other mobile medical staff. We are surprised at the low frequency of isolation of MRSA from staff reported from the Royal Free Hospital. This low frequency may be due to an insensitive sampling technique, the choice of sites for sampling, or the promptness and frequency of sampling after staff have cared for MRSA carriers. We use swabs moistened in peptone water or saline immediately before use and incubate them in an 8% salt broth; this is more sensitive than plating swabs directly on agar. It is not clear which sites were sampled by Bradley et al. We would recommend the nose and abnormal skin; we have isolated the MRSA from eczematous skin and innocuous, clinically uninfected lesions such as gnat bites and a cat scratch. We have also isolated MRSA from other sites such as the hands and the throat. When nasal sampling of the same group of nurses on our ITU was carried