GLOMERULONEPHRITIS AND ORGANIC SOLVENTS

1126

death, active expiration during mechanical ventilation for the

<

Control

cases

o

Clinical

subjects

t

Results on clinical subjects after C. P.A. P. treatment

respiratory distress syndrome,and the grunting expiration seen both in infants with respiratory distress, in patients with asthma and emphysema and in hypoxaemic lambs. To this list could be added the prolonged expiration and expiratory apnoea seen during ventilation by high frequency oscillation, which is abolished by

vagotomy.33

Is there a common link between these widely disparate conditions? One possibility is that overdistension of bronchi or bronchioles may occur in all. This could either be due to alveolar 4 instability, with a relative shift in volume from alveoli to airways,4 or to generalised overinflation. Further investigation could change both our understanding of respiratory control and our textbooks. A century later, even the best texts omit the second and third of the vagal reflex responses to inflation which Breuer and Hering

described.5

Department of Paediatrics, John Radcliffe Hospital, Oxford OX3 9DU

E Self-steering of respiration through the nervus vagus. Translated by Ullmann E. In: Porter R, ed. Breathing: Hering-Breuer Centenary Symposium. London: Churchill, 1970: 359. 2. Greenough A, Woods S, Morley CH, Davis JA. Pancuronium prevents pneumothoraces in ventilated premature babies who actively expire against ventilator inflation Lancet 1984; i: 1-3. 3. Banzett R, Lehr J, Geffroy B. High frequency ventilation lengthens expiration in the anaesthetized dog J Appl Physiol 1983; 55: 329-34. 4. Potter EL, Craig JM. Pathology of the fetus and the infant. London: Lloyd-Luke, 1976. 289. 5. Nunn JF. Applied respiratory physiology. London: Butterworths, 1969: 38. 1.

Phosphatidylcholine as a proportion of total phospholipids in tracheal aspirates in cases and controls. Levels in cases (before treatment) significantly lower than in controls (p<0’001).

WILLIAM TARNOW-MORDI

Hering

COPING WITH CYSTIC FIBROSIS

system. Prolonged "central" apnoea in preterm infants may thus result from stretch receptor inhibition of inspiration rather than primary inspiratory generator failure. Similarly respiratory movements without airflow, usually attributed to airway obstruction, may reflect the active expiratory efforts associated with PEA. Milner and Fagan’s comments notwithstanding, we feel justified in drawing attention to the possible significance of PEA in relation to the cause of sudden infant death syndrome. Cardiothoracic Institute,

Brompton Hospital, London SW3 6HP

D. P. SOUTHALL

Institute of Obstetrics and Gynaecology, London

D. G. TALBERT

Cardiothoracic Institute, London

P. JOHNSON C. MORLEY S. SALMONS J. MILLER

Hospital for Sick Children, London

P.

John

Radcliffe

Addenbrooke’s

Hospital, Oxford Hospital, Cambridge

University of Birmingham

J.

HELMS

P. Prolonged expiratory apnoea and implications for control of breathing. Lancet 1985; ii: 877-79. 2. Talbert 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 1985; i. 727-28. 3. Hill CM, Brown BD, Morley CJ, Barson AJ. Comparison of surfactant in hyaline membrane disease and normal babies. Progr Resp Res 1984; 18: 226-29. 1

Johnson

SIR,-Dr Pinkerton and colleagues’ study (Oct 5, p 761) of the psychosocial problems of patients with cystic fibrosis is methodologically flawed in that patients were rated as "copers" or "non-copers" without these terms being defined. Clinicians will probably rate patients on any or all of the following: frequency of admission (especially if ventilatory function is not severely impaired), anxiety/depression, and complaints about problems in everyday life. It is hardly helpful to report that such indices correlate with the clinicians’ rating of coping or, when little is known about a patient’s coping ability, to regard it as "intermediate". Pinkerton et al, who used the psychosocial adjustment to illness scale (PAIS), do not know if non-coping is "amenable to modification or remediation". There are several standardised measures of psychological status that are considerably more established than the PAIS (for example, Goldberg’s has been used in general medical settings’).However, the PAIS did provide evidence that non-copers have higher scores on anxiety, depression, guilt, worry, and self-devaluation. Pinkerton et al do not seem to have considered the possibility that these patients may have had a depressive illness or anxiety state that, if treated, would convert them from non-copers to copers. Department of Psychiatry, University of Manchester, Manchester Royal Infirmary, Manchester M13 9WL 1.

SiR,—The potential importance of the observations of Dr Southall and his colleagues (Sept 14, p 571) and of Dr Johnson (Oct 19, p 877) is emphasised by the original conclusions of Breuer and Hering in 1868: "Abolition of an inspiration in progress, initiation or prolongation of the expiratory phase, enhancement of active expiration, and retardation of the return of active inspiration: these are the reflex effects of natural or artificial expansion of the 1 lung which are mediated by the vagi."j The four responses represent a spectrum of reflex activity originating from stretch receptors in distended airways. They may underlie several clinical features including apnoea of prematurity, breath-holding spells, profound apnoea leading to sudden infant

FRANCIS CREED

Goldberg DP. Detection of psychiatric illness by questionnaire (Maudsley Monograph no 21). London: Oxford University Press, 1972.

GLOMERULONEPHRITIS AND ORGANIC SOLVENTS

SIR,-Even though doubt has been cast on some of Dr U. Ravnskov’s findings (Sept 7, p 566) another recent case-control study of glomerulonephritis and organic solvents seems to meet Churchill and colleagues’ criteria and thus justify "strategies to decrease exposure and identify susceptibility factors".2Several cross-sectional studies (summarised by Viau3) have demonstrated a higher prevalence of proteinuria and/or enzymuria in workers exposed to organic solvents than in non-exposed controls. We have also found a higher prevalence of unexplained proteinuria in workers compensated by the Belgian Funds for Occupational

1127

Diseases for diseases caused by organic solvents (eg, blood disorders m aromatic hydrocarbon exposure and neurotoxic effects in exposure to trichloroethylene and other halogenated compounds) than in workers with non-pseudotumoral anthracosilicosis and little functional impairment, matched for age, sex, social class, and year of examination. The figures were 8/105 vs 2/105, respectively (Fisher’s exact test, p=0-05). We found no correlation of proteinuria with age, sex,.or duration of exposure. 14 With the possible exception of a small study by Ehrenreich et a the evolution of proteinuria towards chronic glomerulonephritis and renal insufficiency in workers exposed to organic solvents has not been recorded. The magnitude of the risk of chronic glomerulonephritis is, therefore, not known: we estimate that, in Belgium, this risk lies between 20 per million population per year (assuming the same risk as the general population) and 1000 per million (assuming that all cases of chronic glomerulonephritis in Belgium have been recruited from people occupationally exposed to hydrocarbons). (The incidence of terminal renal insufficiency in Belgium in 1983 was 61 per million population, of which about 20% may be estimated to be due to chronic glomerulonephritis. The population occupationally exposed to organic solvents is about 220 000 [Belgian Ministry of Employment, 1981].) Such a level of uncertainty invites preliminary cost-benefit studies before expensive and prolonged controlled prospective investigations in exposed workers. In the meantime, it remains an enigma why, despite ubiquitous, prolonged, and often heavy exposure, so few workers acquire chronic glomerulonephritis.

W. VAN GANSE

J. M. CAROYER

Funds for Occupational Diseases, 1030 Brussels, Belgium

S. VANAVERMAET

1 Bell GM, Gordon ACH, Lee P, et al. Proliferative glomerulonephritis and exposure to organic solvents. Nephron 1985, 40: 161-65. 2. Churchill DN, Fine A, Gault MH Association between hydrocarbon exposure and glomerulonephritis: an appraisal of the evidence. Nephron 1983; 33: 169-72. 3 Viau C. Studies on the chronic nephroloxicity of organic solvents in man and in animal. Doctorate of medical science thesis, UCL, Brussels, 1985. 4 Ehrenreich T, Yunis SL, Churg J. Membranous nephropathy following exposure to volatile hydrocarbons. Envir Res 1977; 14: 35-45.

CANCER OF THE HEAD AND NECK: ARE WE DOING ANY BETTER?

SiR,—The director of the US National Cancer Institute has lately been reported as saying "We’re saving thousands of lives today that weren’t saved years ago".Certainly this should be true of headand-neck cancer, considering the advances made in the past 25 years

(table 1). The details of all patients with a head-and-neck tumour seen by one of us (P. S.) since 1962 have been stored prospectively, on cards at first and for the past 8 years on a microprocessor. The data bank now contains details of 3608 patients. From this store we eliminated all patients who did not have a squamous cell carcinoma, those who did not have histological confirmation of their disease, those with a tumour of the lips or skin, those with a secondary deposit in the nodes in the neck from an undiscovered primary tumour, those initially treated elsewhere, and all those treated since Jan 1, 1980. This left 1225 patients with a histologically proven squamous cell carcinoma of the upper air and food passages who had been potentially cured by treatment but were at risk of recurrence. TABLE I-ADVANCES IN TREATMENT OF HEAD AND NECK CANCER FROM

1960 TO 1965

TABLE II-SIGNIFICANCE OF PROGNOSTIC FACTORS FOR SURVIVAL TO

5 YEARS

Comparison with

GC 0,

No, T"

and

tumour

of nose, sinuses,

We subjected data on this group dependent variable being survival to

nasopharynx,

and

ear.

multivariate analysis, the 5 years. The vast majority of deaths from head-and-neck cancer occur within 2 years, and survival to 5 years can almost certainly be regarded as a cure. The independent variables and the result of the analysis, including the year when the patient was first seen, are shown in table 11. The regression coefficient for year of initial treatment was nonsignificant. There were several other unexpected findings: T (tumour) stage, as defined by the UICC, was not a very significant predictor of survival because of confounding by N (node) stage: survival decreased for increasing T stage (except for T 2) but this is largely due to the fact that larger tumours are more likely to metastasise to nodes in the neck. Age and general condition (ECOG definition) proved to be very important prognostic factors, but they are not allowed for in the UICC classification. A disquieting feature is the advanced stage at which the patients presented for treatment, where the position is worsening-15% of patients seen in the 1960s had a stage T3 or T4 tumour, 27% in the 1970s, and 28% in the 1980s. Clearly in head-and-neck cancer we are not curing any more patients than we were 25 years ago, although reconstruction and rehabilitation have almost certainly improved the patient’s lot. to

Department of Otorhmolaryngology, University of Liverpool, Royal Liverpool Hospital, Liverpool L69 3BX 1. Anon.

Questions about

cancer statistics

PHILIP M. STELL M. S. MCCORMICK Lancet 1985;

i:

41.

DNA SEQUENCE POLYMORPHISMS IN THE APOLIPOPROTEIN A-I/C-III GENE CLUSTER

SiR.—Dr Ferns and his colleagues (Aug 10, p 300) report that in survivors of myocardial infarction there is a significant increase in the frequency of a DNA sequence variant (S2) in the apolipoprotein A-I/C-III gene cluster. The variant is one which produces an additional cleavage site for the restriction enzyme SstI in the fourth exon of the apolipoprotein C-III gene. It was detected in 21°70 of patients and 4% of controls. It is suggested that the variant may be a "genetic indicator for predisposition to myocardial infarction". Scotland is thought to have a higher incidence of coronary heart disease than any other country. In a study of a Scottish population sample designed to determine allelic frequencies of DNA sequence polymorphisms within apolipoprotein genes we have so far tested 117 randomly selected subjects (average age 49): 28 (24%) are heterozygous (genotype Sl/S2) for the S2 variant in the apo-C-III gene. DNA was digested with the endonuclease Sacl, a common isoschizomer of the enzyme Sstl, and hybridised with the 32P-labelled apo-A-1 gene probe, pB-AI, kindly provided by Dr F. E. Baralle.We have also tested 65patients under the age of 55years who were admitted to a coronary care unit and had a confirmed diagnosis of a recent myocardial infarction. 11 patients (17%) were heterozygous for the rare S2 allele. This proportion is not significantly different from that described by Ferns and his colleagues but the frequency in the population sample is