925 interests through courts of law after April, 1974, may well depend on the extent to which they feel they can really influence the future decision-takers. If the regional and area health authorities have vigorous members who are seen by patients to be acting on their behalf and are seen to be accountable to them rather than to the Department or the Treasury, litigation in Britain may remain as a blunt and expensive instrument of last resort. On the other hand, if the future members are seen as " pawns of the bureaucracy "as many people fear they may be with such a high level of selection rather than election-alternative and more effective channels of action will be sought. Misgivings that the new N.H.S. will be all too bureaucratic have been heard from every side of the Lords and the Commons. On the Second Reading of the Reorganisation Bill in the Commons criticism from the Government’s backbenches included, for example, " comments that the Bill was " inadequate " and top heavy in management2 and that " public participation should not be denied and that health-care organisations should be characterised by the existence of widespread public involvement in their decisions ".s There seem to be a number of reasons for Standing Committee G to take time and care to decide whether patients should be given only the " teeth of publicity " in community health councils and the tightly circumscribed help of an overloaded Health Commissioner.
ANTITRYPSIN DEFICIENCY AND ADULT CIRRHOSIS
OF the several inherited metabolic defects associated with hepatic cirrhosis, some may present in childhood and others (such as hxmochromatosis) in adult life.4 Deficiency of alpha antitrypsin in association with neonatal hepatitis and cirrhosis was described by Sharp and his co-workers in 1969.5 Alpha antitrypsin (&agr;1 A.T.), a glycoprotein synthesised by the liver, inhibits trypsin and other proteases in vitro. Severe deficiency of the protein has been linked with pulmonary emphysema in adult life6 progressive liver disease in childhood,and, rarely, with both pulmonary and liver disease. But it is also consistent with lifelong good health. Fagerhol and Laurell, using starch-gel electrophoresis and subsequent antigen-antibody crossed electrophoresis, have distinguished many genetic variants of oci. A.T., constituting the Pi (protease inhibitor) system.9 Some 11 alleles and 21 phenotypes have so far been identified. Most individuals are homozygous for PiM gene. However, between 2% and 12% carry variant genes, some of which do not alter the serum concentration of The major deficiency allele is designated Ki A.T. PiZ, and homozygotes for this allele account for all 2. Hansard, March 26, 1973, col. 983 (Dr Stuttaford). 3. ibid. col. 1024 (Mr Arthur Jones). 4. Stanbury, J. B., Wyndgaarden, J. B., Fredrickson, D. S. (editors). The Metabolic Bases of Inherited Disease. New York, 1966. 5. Sharp, H. L., Bridges, R. A., Krivit, W., Freier, E. F. J. Lab. clin. Med. 1969, 73, 934. 6. Br. med. J. 1973, i, 1. 7. Porter, C. A., Mowat, A. P., Cook, P. J. L., Haynes, D. W. G., Shilkin, K. B., Williams, R. ibid. 1972, iii, 435. 8. Glasgow, J. F. T., Lynch, M. T., Hercz, A., Levison, H., SassKortsak, A. Am. J. Med. 1973, 54, 181. 9. Fagerhol, M. K., Laurell, C. B. Clinica chim. Acta, 1967, 16, 199.
currently recognised cases of severe &agr;1 A.T. deficiency, where the serum concentration is 10-15 % of normal values (200-400 mg. per 100 ml.). Other phenothe
associated with intermediate
The mechanism by which Ki A.T. deficiency produces liver damage is not understood. Electron
microscopy of liver-biopsy specimens shows amorphous material antigenically similar to &agr;1 A.T. within the rough endoplasmic reticulum which can also be seen as P.A.s.-positive staining material after prewith diastase on routine sections.1O This easily be missed on hæmatoxylin-andeosin-stained sections; it has not been identified chemically or enzymatically as al A. T., 11 though it is antigenically similar. All patients with &agr;1 A.T. deficiency have it, whether liver function is normal or severely deranged, so it is unlikely to be the cause of the liver disease. It may represent defective synthesis or impaired release of the protein from the hepatocyte. How then is the liver damage produced ? In vitro the glycoprotein inhibits many proteolytic enzymes such as trypsin, thrombin, plasmin, pancreatic elastase, and leucocyte proteases. One suggestion is that severe deficiency may increase the vulnerability of the liver to noxious agents such as Australia antigen.7 Partial deficiency of Ki A.T. together with cirrhosis has lately been reported by Campra et al. 12 in an adult with SZ phenotype for the Pi system. The serum level of &agr;1 A.T. was approximately 60% of normal. Light and electron microscopy of liver-biopsy specimens revealed amorphous material in the rough endoplasmic reticulum antigenically similar to &agr;1 A.T. No evidence of a pulmonary defect was observed. A paper by Cohen and others 13 describes another adult with more severe deficiency of serum &agr;1 A.T., who had both pulmonary and liver disease and similar microscopical findings; these workers do not report the phenotype for the Pi system. Probably most patients with severe &agr;1 A.T. deficiency have cirrhosis in childhood. But the probability that some with intermediate levels may be unusually susceptible to liver damage is worth bearing in mind. This inherited metabolic defect can and should be excluded as a cause of cirrhosis in the adult. treatment
THE EMPTY SELLA
THE intriguingly named " empty-sella syndrome " has evolved from a curiosity to a well-characterised clinical entity. In 1951, Busch,14 describing the necropsy appearances of the diaphragma sellx and sella turcica in 788 individuals without known pituitary disease, observed that the diaphragm was commonly vestigial and that in such cases the pituitary gland tended to be flattened and the pituitary fossa was at first glance empty. These features were present in 40 of his cases (34 female and 6 male). In such patients the sella turcica forms an extension of the subarachnoid space and is partly filled with cerebrospinal fluid (which may 10. Talamo, R. C. J. Allergy clin. Immun. 1971, 48, 240. 11. Favara, B. E., Franciosi, R. A., Silverman, A. Pediat. Res. 1972, 6, 378. 12. Campra, J. L., Craig, J. R., Peters, R. L., Reynolds, T. B. Ann. intern. Med. 1973, 78, 233. 13. Cohen, K. L., Rubin, P. E., Echevarria, R. A., Sharp, H. L., Teague, P. O. ibid. p. 227. 14. Busch, W. Virchows Arch. path. Anat. 1951, 320, 437.
replaced by air at pneumoencephalography). patients are said to have an idiopathic or primary empty-sella syndrome, as distinct from the condition which sometimes follows surgery or radiotherapy. Most patients with the idiopathic empty-sella syndrome have been investigated for a presumed pituitary tumour. The clinical features and hypothalamic/pituitary/endocrine function have now been described in altogether 60 patients, law 18of whom 53 were women, most of them middle-aged and obese. The presenting symptoms were generally non-specific-headaches, sinusitis, or syncope-with the interesting exception of 7 patients in one series 15 who had spontaneous cerebrospinal-fluid rhinorrhoea. Conspicuously absent was any deficiency in the visual fields. 6 cases were diagnosed as having, or having had, benign intracranial hypertension. No patient had a cerebral tumour. On X-ray the sella turcica was enlarged in most, but not all, instances; often it was symmetrically ballooned rather than deformed. The emptiness of the sella was demonstrated by air encephalography in 52 cases, at operation in 6, and at necropsy in the remaining 2. Only 3 of the patients in the four series 15-18 had symptoms of endocrine disorder: 1 had primary myxcedema; 1 had secondary hypothyroidism, which was the manifestation of panhypopituitarism; and 1 had longstanding untreated acromegaly. None had diabetes insipidus. The endocrine function of two-thirds of the patients was judged to be entirely normal. The pituitary/endocrine disturbances defined in the remainder were generally subtle: the commonest were impoverished secretion of growth hormone in response to hypoglycxmia (in about a third of the patients tested) and diminished secretion of gonadotrophins. Only exceptionally was there any suggestion of impairment of pituitary control of thyroid and adrenal glands. The xtiology of the empty sella is unknown. An incomplete diaphragma sellar is a precondition; and the most generally accepted hypothesis is that transmission of a normal or raised cerebrospinal-fluid pressure results in flattening of the pituitary, followed by bony remodelling. Is there an associated clinical syndrome? Except in cases with cerebrospinal-fluid rhinorrhcea, investigation has usually been initiated by the chance observation of sellar enlargement on X-ray. The headaches, which were the presenting complaint in a third of the cases, were variously described by the patients and seemed non-specific in character. 18 Existing knowledge suggests that this is an uncommon These
condition which does not cause an identifiable clinical syndrome. It is benign in nature and does not progress to pituitary failure. Cerebrospinal-fluid rhinorrhoea, which may be complicated by meningitis, requires treatment by packing of the empty sella with muscle.19 In the absence of rhinorrhoea the chief hazard to the patient is investigation to exclude a pituitary tumour or, worse, surgery or radiotherapy to the pituitary without previous air encephalography. 15. Brisman, R.,
Hughes, J. E. O., Holub, D. A. J. clin. Endocr. 1972, 34, 570. 16. Neelon, F. A., Goree, J. A., Lebovitz, H. E. Medicine, Baltimore, 1973, 52, 73. 17. Caplan, R. H., Dobben, G. D. Archs. intern. Med. 1969, 123, 611. 18. Hodgson, S. F., Randall, R. V., Holman, C. B., MacCarty, C. S. Med. Clins N. Am. 1972, 56, 897. 19. Brisman, R., Hughes, J. E. O., Mount, L. A. J. Neurosurg. 1969, 31, 538.
ATTITUDES TO DRUGS THE inconsistency in public attitudes towards the non-medical use of drugs was much on the mind of many who gathered in London last week for the threeday Anglo-American conference1 on drug abuse. Look at Texas, Governor Raymond P. Shafer exclaimed, where it was a more serious matter to offer a man a reefer than to castrate him. And the very term
" drug abuse " often determined the course of discussion because it really meant " the use of drugs of which society disapproves ". Then there was the Dr Jock Young saw in the prevalent view that myth " people on the fringe " were alone involved, whereas one of the features of drug use was its ubiquity. The film, The French Connection, illustrated how an aggressive system was established ostensibly to protect the whole of society from being damaged by drugs, though in fact this supposed sequence was an irrational reversal of causality, since the aggression came before the drugs. Dr Young’s tumultuous assault on widely accepted attitudes brought a perhaps not unexpected response from a few in his audience. Admittedly his dress and style are not everyday manifestations at the Royal Society of Medicine, but that was a poor reason for the departure (a few minutes after he began) of a number of apparently aggravated individuals. Had they stayed, they might have heard something to their advantage-or that of their patients. As Dr Peter Chapple remarked, there is some danger in any renewal or extension of hostility between the medical profession on one side and the sociologists, criminologists, and associated students of human behaviour on the other. They must all come to terms if they were to explain and counter the damage of drugs. Other sessions of the conference reflected more of that desirable concord; and Mr William Deedes, M.P., probably summed-up the middle line of action when he advocated a cautious move away from repression of drug-takers and towards " informal social control ", though change could proceed only as fast as the accumulation of medical and social evidence permitted. As far as Britain had gone, Lady Wootton was less than satisfied with the rate of progress of the Misuse of Drugs Act 1971, which was at last about to come into force. By now the Act embodied the political thinking of three years ago, and the climate of opinion, especially concerning the use of cannabis, had changed. Yet the Act specified the same maximum sentence (14 years) for trafficking in cannabis and in hard drugs. And would 14 years be a greater deterrent than the 10 years prescribed by the present law ? The changing views on cannabis had contributed to anomalous action by magistrates and police. At the Reading pop festival of 1971, the Thames Valley Constabulary searched nearly 2000 persons and charged 119 with possession; but other festivals that year and later underwent no such scrutiny. Lady Wootton’s words may have sounded a little rueful at the modest impact on the law achieved by her subcommittee’s report on cannabis in 1969 2 ; but the twinkle in her eye may have denoted some small satisfaction at what had been accomplished elsewhere. 1.
Sponsored jointly by the Royal Society of Medicine, London, the Royal Society of Medicine Foundation Inc., New York. See Lancet, 1969, i, 139.