1198

because of inadequate doses. Meanwhile the Ministryof Health and local health authorities will be keepinga look out for any disagreeable moves by the flies ;from the epidemiologist’s point of view they seem to beremarkably well behaved at the moment.

1. See Lancet, 1952, i, 350.2. Ibid, 1952, ii, 477.3. Stumpf, H. H., Wilens, S. L. Arch. intern. Med. 1953, 91, 304.4. Dorfman, R. I. In The Hormones. New York, 1950; vol. 2,

p. 42.

HEPATIC CIRRHOSIS AND PROSTATICENLARGEMENT

WHEREAS the secretion of hormones is exclusivelya function of the endocrine glands, their excretion andinactivation, by which a balance is maintained, appearto be mainly controlled by the liver. In the liver they areconverted to inactive derivatives or to compounds morereadily excreted by the kidneys than the unchangedhormones. Although much of the recent work on thissubject has been concerned with the steroid hormones,there is also evidence that thyroxine and the posteriorpituitary antidiuretic factor also undergo at least partialinactivation in the liver. In view of this extremelyimportant hepatic function, it is not surprising thatsigns of endocrine disturbanoe are now well-recognisedfeatures of liver disease, especially of cirrhosis.1 2 Thesesigns arise predominantly from hypercestrogenism, andthey include gynsecomastia, testicular atrophy, and lossof libido in men, and menstrual disorders and impairedfertility in women.

Fortunately the results of hormonal imbalance are notalways a disadvantage to the patient. This is wellshown by Stumpf and Wilens 3 in their study of theincidence of prostatic enlargement in portal cirrhosis.Their figures were collected from necropsies on 333

patients with cirrhosis and 359 non-cirrhotic controls.Both groups consisted entirely of men over 50 years old.In the control group 53% had gross prostatic enlarge-ment-a proportion that agrees well with other publisheddata for this condition ; but in the cirrhotic group only30% had enlarged prostates. If only the moderate andsevere cases of enlargement are included, then thedifference is even more striking-namely, 30% in thecontrols and 8% in those with cirrhosis-and becomesstatistically significant. Not only were those with cir-rhosis less likely to get prostatic hypertrophy, but thefigures also indicated that when the prostate did enlargeit did so later than in the controls. For example, in themen with severe cirrhosis in the age-group 50-69, thefrequency of moderate or severe prostatic hypertrophywas 6%, compared with 28% in the controls, whilst inthe 70-79 age-group the corresponding figures were 17%and 23% respectively. Confirmation of this inverserelation between cirrhosis and prostatic enlargement isprovided by the much greater incidence in the controlgroups of the secondary results of prostatic hyper-trophy-e.g., hypertrophy of the bladder (which was twiceas common) and hydro-ureter (which was four times ascommon).

In speculating on the cause of these differences Stumpfand Wilens rightly say that " the condition is not

necessarily hormonal in nature, yet the fact that cestro-gens are not properly inactivated in liver disease suggeststhat these may be involved." It is well established

experimentally that oestrogens can antagonise the stimu-lating effect of androgens on the prostate in castratedanimals.4 Moreover, the beneficial effect of castration

upon benign prostatic hypertrophy suggests that thestimulating effect of the testicular androgens is of

significance in the pathogenesis. If this be so, then the

antagonistic effect of the hypercestrogenism associatedwith cirrhosis could account for the lower incidence ofprostatic hypertrophy. An alternative or contributing

mechanism may perhaps be related to the fall in 17-ketosteroid excretion in cirrhosis, 5 Testosterone, whichhas a hydroxyl group on carbon atom 17, is much lessactive in stimulating the prostate than the androgens,such as androsterone, with a ketone group at C17.6 Ifthe fall in ketosteroid excretion in cirrhosis is due to

inadequate oxidation of the testosterone type of androgento the androsterone type, then the stimulus to prostatichypertrophy would be much reduced. It is apparent,however, that until more is known of the aetiology ofbenign prostatic enlargement, any explanation of theinhibitory effect of cirrhosis can only be speculative.Nevertheless, this effect of cirrhosis strongly supports thehormonal-imbalance theory, and encourages the viewthat prophylaxis, and perhaps treatment, may one daybe successfully achieved by hormone therapy alone.

5. Schedl, H. P., Ditto, K., Bean, W. B. J. Lab. clin. Med. 1953,42, 116.

6. Selye, H. Textbook of Endocrinology. Montreal, 1947; p. 613.7. Negus, V. E. Comparative Anatomy and Physiology of the

Larynx. London, 1949.8. Stuart, T. P. A. Proc. roy. Soc. 1891-92, 50, 323.9. Ardran, G. M., Kemp, F. H., Manen, L. Brit. J. Radiol. 1953,

26, 497.10. Ardran, G. M., Kemp, F. H. Ibid, 1952, 25, 406.11. Ardran, G. M., Kemp, F. H., Truelove, S. C. Gastroenterologia,

Basel, 1953, 79, 361.

CLOSURE OF THE LARYNX

THE comparative anatomical studies of Negus 7indicate that the larynx is primarily a sphinctericmechanism designed to prevent the entry of water orother noxious substance into the lungs and to regulatethe flow of air to and from the lungs ; the production ofsounds appears to be a later development. Complete orpartial obliteration of the laryngeal lumen duringvocalisation, swallowing, and other manoeuvres is usuallydescribed as closure of the glottis (apposition of the vocalcords). It is believed that the vestibular folds mayprevent expiration, but they are not thought to play anypart in normal phonation. Muscular closure of the

superior aperture of the larynx was described by Stuart.8By means of cineradiography in the anteroposterior andlateral projections, combined with the usual method ofexamination, Ardran et a1.9 have obtained furtherinformation on laryngeal behaviour.

During quiet breathing the laryngeal lumen is wideopen and little movement takes place. The vocal foldsare turned upwards over the laryngeal ventricles so thatthe airway is not obstructed. When closure occurs thewhole of the airway from the level of the vocal folds tothe superior aperture of the vestibule is obliterated bysphincteric muscular action. Complete or partial closuremay take place while holding the breath, coughing,performing any act that requires rigidity of the trunkmuscles, and swallowing. There is also a mechanism

whereby the vocal folds are turned down across the

airway with narrowing of the airway above, and speechis always associated with partial closure of the vestibuleand vestibular folds.

This sphincteric closure of the larynx from the levelof the vocal folds upwards protects the airways duringthe act of swallowing 10; the epiglottis turns down overthe mouth of the larynx, but this happens only towardsthe end of the act of swallowing and after the bulk of thebolus has passed the entrance to the larynx, which maystill be open at the time. A little of the bolus commonlyenters the vestibule and may even descend as far as theventricle without causing coughing and without thesubject being aware of the fact. In normal people thisportion of the bolus is always expelled on the obliterationof the laryngeal lumen when the last of the bolusleaves the pharynx. Patients with a disorder of thelarynx-for example, in acrosclerosis ll-may fail toclear the vestibule of bolus residues in the normalway.