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depended on randomisation of subjects to have disposed of anypotential bias from this source (and from many others). This is,after all, the unique virtue of randomisation: it eliminatesbiases from characteristics which we cannot measure.We are sending a draft of a detailed report, which is in

preparation, to Dr. Watson and Professor Yudkin, in order tosatisfy fully their understandable desire to evaluate the studycritically.

SEYMOUR DAYTONMORTON LEE PEARCE.

Medical Service,Wadsworth Veterans Hospital andDepartment of Medicine, U.C.L.A.,Los Angeles, California, 90073.

ARGININE INFUSION AND GROWTH-HORMONESECRETION

WYLIE C. HEMBREEGRIFF T. Ross.

Endocrinology Branch,National Cancer Institute,

Bethesda, Maryland, U.S.A.

SIR,-Unlike Dr. Best and his colleagues (July 20, p. 124),we have found that arginine infusion is an effective stimulus topituitary secretion of human growth hormone (H.G.H.). Ourconclusion is based on results of studies designed to establishthe minimum dose of arginine necessary to produce an increasein plasma-H.G.H. levels in 16 normal subjects and to test thecomparative efficacy of infusions of this agent with intravenousinjections of insulin and piromen in the same subjects. Plasmalevels of immunoreactive H.G.H. were measured by the methodof Odell et al.l: (1) after 30-minute infusions of argininehydrochloride in hypotonic Ringer’s solution at three doselevels (125 mg., 250 mg., and 500 mg. per kg. body-weight);(2) during reduction of blood-glucose to 50% or less of fastinglevels by intravenous injection of insulin (0-05-0-10 unit perkg. body-weight); and (3) after intravenous administration of’Piromen’ (0-6 µg. per kg. body-weight). The volunteers (12women and 4 men aged 19 to 22 years) were hospitalised for thetest period and maintained ambulatory work schedules excepton test days. The studies were done in random order, at

intervals of at least 4 days. All tests were done between 6 A.M.and 9 A.M.

Infusion of arginine at a dose of 500 mg. per kg. wasassociated with an increase of plasma H.G.H. to concentrationsof 10 ng. per ml. or more in all 16 subjects. Similar elevationswere observed in 12 of 13 subjects after insulin-induced

1. Odell, W. D., Rayford, P. L., Ross, G. T. J. Lab. clin. Med. 1967,70, 973.

PEAK PLASMA-H.G.H. CONCENTRATIONS (ng. PER ml.)

* Values not included in calculations of means and standard errors becausethey do not represent an elevation above resting H.G.H. levels.

hypoglycaemia and after intravenous piromen. In women, a

comparison of mean peak H.G.H. levels attained during the studyshowed no significant differences in the responses to arginine,insulin, and piromen (see table). In men, the mean response toarginine was the same as that noted in women, but the meanresponses to insulin and piromen were higher. However, thesmall size of the group and the variability of response did notpermit a statistically valid comparison. In women the responseof H.G.H. levels to arginine was not dose-related. Only 1 of the4 men showed a rise in plasma-H.G.H. after 125 mg. arginineper kg. body-weight, but all 4 showed a rise of more than 10 ng.per ml. after infusion of 500 mg. arginine per kg. body-weight.These findings are compatible with the sex differences previouslynoted 2 and suggest that arginine may cause elevation of H.G.H.levels in women at a considerably lower dose than in men.The lack of H.G.H. response to arginine in some subjects

described by Dr. Best and his colleagues is not typical of earlierreports and may have been related to the activity of thesubjects before infusion. Spontaneous fluctuations and occa-sional elevation of plasma-H.G.H. associated with saline infusionsemphasise that any study of plasma-H.G.H. levels must beperformed under controlled conditions which minimise theinfluence of other metabolic or physical factors. Nevertheless,the consistent response of plasma-H.G.H. levels to arginineinfusion at a dose of 500 mg. per kg. body-weight in normalsubjects has established it as a useful test in the evaluation ofpatients with hypothalamic-pituitary disease,4 and we wouldrecommend its continued use for this purpose.

FEEDING THE NEWBORN

SIR,-We feel that Dr. Barrie (Nov. 30, p. 1158) paints toogloomy a picture of the effects of feeding on respiratoryfunction in the newborn.We have studied the effects of feeding on respiratory

mechanics using an oesophageal balloon passed through themouth and a nasal coupling device which remained in situ forseveral hours before the study, to’ensure comparability of thepre- and post-feed studies. The infants were bottle-fed, thenasal coupler being left in position during the feed, and studieswere performed with the infant lying on his side. In this

position, we found that oesophageal-pressure swings did notdiffer significantly from those obtained in the supine position,although the absolute pressure might differ. Tidal-volumemeasurements were made by electronic integration of flow-signals obtained from a pneumotachygraph attached to thenasal coupler. -

Twenty-three healthy infants, weighing 1700-3845 g.,studied during the first 3 days of life, showed no consistentresponse to feeding, the feeds given being smaller than inDr. Barrie’s examples. The oesophageal-pressure swing fellafter feeding by an average of 0-6 cm. of water; and minutevolume, calculated from ten consecutive breaths, rose on

average by only 34 ml. The periodic respiration which weoccasionally observed after feeding was attributed to the sleepwhich normally followed the feed. When evidence of mso-phageal regurgitation was looked for, by the passage of a secondcesophageal tube, none was found.We suggest that the high incidence of respiratory irregulari-

ties and cesophageal regurgitation observed by Dr. Barrie wasdue to a combination of the unusually large volumes of feedgiven, nasal obstruction by the two size-6F feeding-tubes(Polgar and Kong have stated that nasal resistance maycontribute up to 70% of total lung resistance in newborninfants; occlusion of one nostril must increase this contribution),the presence of an intragastric tube, and the supine position in

2. Merimee, T. J., Burgess, J. A., Rabinowitz, D. J. clin. Endocr. Metab.1966, 26, 791.

3. Parker, M. L., Hammond, J. M., Daughaday, W. H. ibid. 1967, 27, 1129.4. Hembree, W. C., Ross, G. T. Clin. Res. 1968, 10, 268.5. Polgar, G., Kong, G. P. J. Pediat. 1965, 67, 557.

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which the infants were studied. In normal circumstances, whena baby is fed in a semi-recumbent position and laid on his sideafter the feed, these problems are unusual, as noted by Dr.Davis last week (p. 1397).

GEORGE RUSSELLELIZABETH A. FEATHER.

University Department of Child Health,Foresterhill, Aberdeen AB9 2ZD.

HOSPITAL SCIENTISTS

D. E. B. POWELL.

Pathology Department,Bridgend General Hospital,

Bridgend, Glamorgan.

SiR,-It is unfortunate that your leader (Dec. 21, p. 1331)should be largely a resume of the Zuckerman report, and showmore concern in your conclusions with sniping at the corres-ponding editorial in the British Medicallournal, and hospitalpathologists, than examining the report itself in a criticalfashion.The bulk of diagnostic work in National Health Service

hospitals is done in regional district hospitals. In the light ofthis the composition of the Zuckerman committee, for all theindividual distinction of its members, was extraordinary. Arecurring theme was the inadequacy of the career prospects fornon-medical scientists. However, the committee avoided

making a factual (and financial) comparison of careers forscience graduates in related professions, such as teaching andindustry, with those already available within the NationalHealth Service. The nature of the " senior principal " and" special post above senior principal " is left to the imagination.You attack the concept that " bridge-building

" should bedone only by medically qualified people. In so far as thenon-medical scientist has a vital contribution to make to thepatient’s welfare, your point is, of course, valid. But the dangeris now that we throw the baby out with the bath-water. Adiagnostic department serves doctors of all grades and

experience both within and outside the hospital service. Thesedoctors frequently need and value the help that can best comefrom a laboratory worker who has a real appreciation of theclinical context. " Patients tethered by wire and tube to

apparatus tended by non-pathologists " are already in the careof a clinician, and in any case are hardly representative of thegreater part of laboratory work undertaken.Laboratory and diagnostic services have expanded out of

recognition in recent years, and clearly much remains to bedone. But it appears that all the various Government-

sponsored reports must in the end resort to advocating newmachinery, more committees, and further administration.

Anyone concerned in the day-to-day working of these servicescould see many ways in which the existing machinery andresources might be deployed to improve service.

RADIATION TREATMENT OF THYROTOXICOSIS

M. HULBERT.

Department of Radiotherapy,St. Mary’s Hospital,

London W.2.

SIR,-The article by Dr. Philp and his colleagues is of greatinterest (Dec. 21, p. 1307). The failure of beamed radiation toproduce a therapeutic effect in patients with thyrotoxicosismay have been due either to the application of a single massivedose instead of fractionated exposures or to the unexplainedadditional treatment with sulphur-containing antithyroiddrugs-thiourea, for instance, being a radiation-protector. Itis just as well that the experiment gave a negative result.Otherwise it might have led to the revival of a method whichwas abandoned for good reasons. The long-term results wereunsatisfactory, and the development of carcinoma of thethroat many years after external irradiation for benignconditions does not recommend such treatment.

1. Goolden, A. W. G., Br. med. J. 1951, ii, 1110. Hollinger, P. M.,Rabbett, W. F., Laryngoscope, 1953, 63, 105. Raven, R. W., Levin-son, V. B., Lancet, 1954, ii, 683. Slaughter, D. P., Southwick, H. W.Archs Surg. 1957, 74, 420.

EARLY DETECTION OF CANCER

STANLEY WAY.

MAURICE SUTTON.

SIR,-Professor Brooke’s disputation of dogma (Dec. 14,p. 1289) is timely and one of the most thought-provokingpapers that you have published in recent years.

Since he states that " The gynxcologists have shown usthe way ", may I repeat what I wrote in 1963 1: " any cancerof the cervix which can be seen by the eye or felt by theexamining finger is more than a potential killer and cure isby no means certain " ? In a much larger organ like thebreast, these remarks of mine are even more cogent, andProfessor Brooke’s most pertinent statement is, " She knowsit has not been palpable for more than a month." Anymalignant lump that can be felt in a large organ like thebreast has obviously been there too long to give comfort toeither the patient or the surgeon, and " self-palpatation " isin reality no more than self-deception.My old friend, the late Dr. George Papanicolaou, and I

discussed exfoliative cytology of breast tumours " ad

infinitum", and agreed that cytology had little to offer in thisdisease.

Like Professor Brooke, I believe that this is no cause for

pessimism, but rather that we should seek more diligently,not for early diagnosis (which means diagnosing at 6 A.M.instead of noon), but for the diagnosis of early breast cancer,and at the present moment thermography, coupled with mam-mography, offers some hope-it is at least a move away fromself-deception.

Gosforth,Newcastle upon Tyne 3. STANLEY WAY.

SIR,-I agree with Professor Brooke that early detectiondoes not always mean the detection of early cancer. The

important point is, however, that in any individual patient theearlier the cancer is treated the better are the results.North Middlesex Hospital,

London N.18. MAURICE SUTTON.

ATROPINE PSYCHOSIS

SIR,-Dr. Adgey and her colleagues (Nov. 23, p. 1097) haveshown the extreme frequency and importance of bradyar-rhythmias during the early stage of myocardial infarction.

According to the commonly accepted view the drug of choicefor sinus bradycardia is atropine in small doses, repeated every3-4 hours (preferably intravenously in 0-3-0-5 mg. doses) tospeed the heart-rate. Dryness of the mouth, blurred vision,and urinary retention are among the best known peripheralside-effects. Shillingford has briefly noted that " less commonlyhallucinations occur 11,2 and Kimball and Killip 3 mentionedthat four of their patients became frankly psychotic after havingreceived several doses of atropine during 24 hours.During the past half year I have seen serious mental aberra-

tion among 30 patients with myocardial infarction, all morethan sixty years old, whose sinus bradycardia has been treatedwith atropine. Slow cerebration, inattention, somnolence, rest-lessness (in a few reaching a delirious state), paranoid ideas, andauditory and visual hallucinations have been seen in at least 5patients. All patients had previously been mentally normal, andtheir symptoms occurred after doses of less than 4 mg. of atro-

pine per 24 hours. In none did heart-failure, shock, or hypoxae-mia seem to be a possible underlying cause. In all, the mentalsymptoms cleared 24-36 hours after withdrawal of atropine.Retrospectively I assume that some of the " cardiac psychosespreviously seen in the ward have been caused by atropine.The symptomatology seems to be identical with the " central

anticholinergic syndrome " of Longo 4 caused by inhibition ofimportant neuronal pathways in the base and central parts of1. Way, S. The Diagnosis of Early Cancer of the Cervix. London, 1963.2. Shillingford, J. Am. Heart. J. 1968, 75, 843.3. Kimball, J., Killip, T. Progr. cardiovasc. Dis. 1968, 10, 483.4. Longo, V. G. Pharmac. Rev. 1966, 18, 965.