1092

raised plasma ultrafiltrable calcium, while reabsorption ofcalcium is not directly influenced; (c) the effects of castrationon bone-mineral metabolism are apparently extrarenal andoccur shortly after castration.

Studies are now in progress to determine whether castrationinfluences calcium metabolism through intervention of otherhormones.

JANUSZ SZYMENDERASTEFAN MADAJEWICZ.

Department of Isotopes,Institute of Oncology,Warsaw 22, Poland.

GASTRIN ANALOGUES AND GASTRIC-SECRETION

TESTS

SIR,-The steadily increasing number of publications on theeffect of the synthetic gastrin analogue I.C.I. 50,123 (N-t-butyloxycarbonyl - p - alanyl - L - tryptophyl - L - methionyl - Laspartyl-L-phenylalanine amide, pentagastrin) on gastric secre-tion 1-10 have apparently not provided the final answers to two

. fundamental questions: the frequency of side-effects, and thedose of pentagastrin which will elicit a

" maximal " acid

response.The side-effects of pentagastrin-sinking abdominal sen-

sations, abdominal cramps, nausea, hypotension, faintness,headache, and general malaise-are reported to occur withwidely differing frequencies.1-3 5 7-9 They seem to be morecommon after intravenous than after subcutaneous adminis-tration.5 11 Although one group of investigators 10 found noside-effects after 1-5 and 7-5 g. per kg. per hour, side-effectswere fairly common in other studies using 6 and 12 g. per kg.per hour.2 s

a However, the side-effects are by no meansrestricted to intravenous administration, but have been reportedafter subcutaneous injections of 4-13 fLg. per kg. I-a 5 7—

apparently most often with doses above 6 µg. per kg., althoughone group of workers stated that " there was no apparentrelationship between the dose and the severity of the

symptoms ".5The dose of pentagastrin needed for a " maximal " acid

response has been discussed by several workers. 1 2 5 8-11 Mostworkers using subcutaneous or intramuscular injections foundthat 6 fLg. per kg. of pentagastrin elicited an acid responsesimilar to that after augmented histamine stimulation, and thatthe acid output did not rise further after 8, 9, or 10 fLg. perkg.1 5 9 The doses of intravenously administered pentagastrinrequired for a

" maximal " acid response vary in the reportscited above. Wormsley et al.2 found peak acid outputs (similarto those after ametazole) in most subjects after pentagastrindoses ranging from 0-6 to 6 g. per kg. per hour; in somesubjects, however, it was not certain that peak acid secretorycapacity had been reached, since an increase in dose-rate

produced side-effects. Konturek and Lankosz 10 found that1-5 µg. per kg. per hour of pentagastrin gave an acid outputsignificantly higher than that after a submaximal dose ofhistamine diphosphate (20 µg. per kg. per hour); and thata five-fold increase of the pentagastrin dose during the sameexperiment’s third hour did not result in a higher acid output,while the acid output after this dose was not significantly higherthan the acid response to histamine diphosphate in a dose of40 µg. per kg. per hour, in the same period. Another group 5found the acid response significantly higher after 5 µg. per kg.per hour of pentagastrin than after 2-5 as well as after 10 µg.1. Makhlouf, G. M., McManus, J. P. A., Card, W. I. Gastroenterology,

1966, 51, 455.2. Wormsley, K. G., Mahoney, M. P., Ng, M. Lancet, 1966, i, 993.3. Logan, C. J. H., Connell, A. M. ibid. p. 996.4. Logan, C. J. H., Brick, I., Roddie, I. C. ibid. p. 999.5. Multicentre Pilot Study. ibid. 1967, i, 291.6. Bank, S., Marks, I. N., Louw, J. H., Tigler-Wybrandi, N. ibid. 1967,

ii, 67.7. Shearman, D. J. C., Finlayson, N. D. C., Murray-Lyon, I. M., Samson,

R. R., Girdwood, R. H. ibid. p. 192.8. Multicentre Study. ibid. p. 534.9. Johnston, D., Jepson, K. ibid. p. 585.

10. Konturek, S. J., Lankosz, J. Scand. J. Gastroent. 1967, 2, 112.11. Makhlouf, G. M. Lancet, Sept. 30, 1967, p. 720. Duthie, H. L.,

Jepson, K., Johnston, D. ibid. p. 841.

per kg. per hour, and the output after 6 (1.g. per kg. per hourhigher than after 12 (1.g. per kg. per hour. e

In your leading article,12 commenting on the first reports onpentagastrin to appear in The Lancet,2—4 you concluded: "Itsuse in the testing of gastric function is, however, complicatedby the side-effects, and it clearly does not fulfil the ideal ofa secretory stimulant without undesirable activity". Pure

gastrin has no side-effects on subcutaneous administration,"and it is possible that the smallest molecule displaying theentire range of physiological properties of natural gastrin inanimal experiments 14-the C terminal tetrapeptide, or " tetra-gastrin "-may get closer to the ideal stimulant for clinical usethan does pentagastrin. We have by now compared the effect oftetragastrin on gastric secretion with that of histamine diphos-phate (40 (Jtg. per kg. subcutaneously) in 52 subjects.15 Theeffects of 2-5, 5, 10, and 20 (1.g. per kg. of subcutaneouslyinjected tetragastrin have been studied in 6, 6, 19, and 21subjects, respectively. With the 2-5 (1.g. per kg. dose theacid response was significantly lower than after histamine,while the mean acid output after 5 µg. per kg. (29-3 mEq. perhour) was similar to that after histamine (32-3 mEq. per hour).With the higher doses of tetragastrin the acid response corres-ponded closely to that after histamine. No side-effects wereencountered in any of the 52 subjects studied. In this respecttetragastrin so far seems similar to pure gastrin; the effect oftetragastrin upon intrinsic factor and pepsin secretion 15 is alsovery similar to the effect of gastrin.16

PAUL RØDBRO.Medical Department F,

Glostrup Hospital, Copenhagen.

K. H. KØSTER.Surgical Department A,

Bispebjerg Hospital, Copenhagen.

TREATMENT OF HEPATIC COMA

SIR,-We have read with interest your leading article (Aug. 5,p. 294). We describe here a successful exchange transfusion wehave lately performed in a patient with hepatic coma due toinfective hepatitis.Ten days before admission to the medical unit of this

hospital, a 32-year-old policeman developed anorexia andmalaise, followed by jaundice a couple of days later. Six daysbefore he had started vomiting and. had developed upperabdominal pain. At this stage he had been admitted to thePolice Hospital, where his condition rapidly deteriorated

despite treatment; after four days he had become drowsy,LIVER-FUNCTION TESTS IN PATIENT WITH HEPATIC COMA BEFORE AND

AFTER EXCHANGE BLOOD-TRANSFUSION

though at times he was agitated and restless. Twelve hoursbefore transfer here he had passed into a state of deep coma.The patient was of good physique, with yellow sclerae.

Painful stimuli elicited no response. The plantar response wasextensor on both sides. Liver-function tests done on variousoccasions are shown in the accompanying table.The patient was treated with prednisolone, 100 mg. daily,

12. Lancet, 1966, i, 1022.13. Makhlouf, G. M., McManus, J. P. A., Card, W. I. ibid. 1964, ii, 485.14. Morley, J. S., Tracy, H. J., Gregory, R. A. Nature, Lond. 1965, 207,

1356.15. Køster, K. H., Rødbro, P., Peterson, H. J. Scand. J. Gastroent. (in the

press). Køster, K. H., Faber, V., Rødbro, P. ibid.16. Wangel, A. G., Callender, S. T. Br. med. J. 1965, i, 1409. Makhlouf,

G. M., McManus, J. P. A., Card, W. I. Gastroenterology, 1967, 52, 787.

1093

and paromomycin (’ Humatin ’), 500 mg. every 4 hours,through a Ryle’s tube, together with 15% glucose solution byintravenous drip transfusion, and parenteral vitamins. After48 hours on this regimen the depth of coma was unchanged.At this stage (i.e., 60 hours after the onset of deep coma, and108 hours after the onset of drowsiness) an exchange transfusionwas performed with 10 pints of fresh heparinised blood. Whilemaking the skin incision and doing the dissection to identify thelong saphenous vein, no local anxsthetic was needed because ofdeep coma; but as the transfusion was coming to an end, thepatient seemed to have some awareness of pain in the groin.Twelve hours after the exchange transfusion the patient, whohad been lying absolutely still, became extremely restless andwas restrained in bed with great difficulty. Plantar responseremained extensor on both sides. Later the depth of comagradually lessened and 30 hours after the transfusion the patientcomplained of headache. At that time he was still confused andnot fully orientated. His confused state gradually improved and38 hours after the transfusion he was able to obey simplecommands and answer simple questions. At this stage theplantar responses became flexor. Improvement was rapidduring the next few hours and 50 hours after transfusion he wasmentally alert and answered all questions rationally. There-after his recovery was uneventful and he is now back at work,after a period of convalescence.Our experience is so far limited to this one case, but we feel

that this form of treatment offers some hope in an otherwisehnmalPCe situation

NAZIR A. CHAUDHARYNASEER AHMAD SHAIKH

MUSHTAQ HASAN.

Dow Medical Collegeand Civil Hospital,Karachi, Pakistan.

TRAINING IN MEDICAL LABORATORY

TECHNOLOGY

SIR The response in your correspondence columnsto the statement from the Institute of Medical LaboratoryTechnology (Oct. 28, p. 935) reflects a widespread endeavour tomaintain high standards of technology and efficiency. Thereis general agreement on a system of coordinated trainingconducted by experts and based on day or block release; andthere should be close liaison between training institutes andworking laboratories. However, laboratories must continue tofunction at all times as efficient working units, and the problemof providing full training facilities is linked with that of main-taining adequate work output of a high technical standard.Whether or not day release is made compulsory, there is littledoubt that it is here to stay: it is also clear that the constraints

imposed by regular staff absences can be overcome only byincreases in technical establishments; but, because of presentfinancial restrictions and shortage of labour, it is unlikely thatearly increases in senior establishments will come about orthat, in any case, these would solve the immediate problem.

In the recent correspondence, no account has been taken ofthose who are willing and capable of giving useful service inlaboratories but who, for various reasons, have no wish toundergo training in depth or to acquire technological qualifica-tions. Much of the work of medical laboratories-clinical,academic, or reference departments-is elementary or repeti-tive, and much of this can be carried out by people withcomparatively little training. Is it not time, as a matter ofnational policy, to encourage employment of a quota of semi-skilled labour in laboratories in order to permit greaterflexibility in educational arrangements for those most suitablefor advanced training ?Recruitment of such semiskilled labour should be based on

recognised salary scales proportional to, but slightly less than,those of technicians in training; and increments could be basedon age, length of service, and, possibly, degree of local responsi-bility. This suggestion in no way implies a lowering oftechnical standards. Most experienced laboratory workersare acquainted with technicians who are excellent at theirdaily work but pass examinations only with great difficulty,if at all.

Surely, employment and recognition of such workers wouldplug some of the obvious leaks in technical establishments,because many who are now deterred by academic handicapswould be encouraged to enter laboratory services. Con-temporary proposals for technicians’ training are to be com-mended for their far-sighted aims and their optimism. Butthis optimism must be modified by the realities of the presentsituation. Only by paying due regard to the pressures on thelower echelons of laboratory workers will a future elite body oftechnologists be created.

G. D. WASLEYR. FRASER WILLIAMS.

Department of Medical Microbiology,St. Thomas’s Hospital Medical School,

London S.E.1.

DERMATOGLYPHICS IN ECTODERMALDYSPLASIA

SIR,—I wish to report briefly my dermatoglyphic analyses oftwo families with hereditary anhydrotic ectodermal dysplasia,since there seem to be findings common to affected individualsand carriers. In this X-linked disorder there are decreasednumbers of sweat-glands in the skin, hypotrichosis, andanodontia. The carrier female usually has symptoms. Sincethe skin is involved, one might expect to find characteristicdermatoglyphic changes, as in this short series.

In family 1 the father was clinically normal; the mother hadthin hair, decreased sweating, and poor teeth; three sons wereall severely affected. In family 2 the father was clinicallynormal; the mother had decreased sweating; three sons wereseverely involved and one son was normal. The dermato-

glyphics of all these people were analysed; the affected ones hadstriking ridge disruption in all areas of palms and soles. Therewas also a tendency for the patterns to be vestigial, particularlyin the third and fourth interdigital and plantar hallucal areas.The c and d digital triradii tended to be absent, vestigial, ordisplaced, and the C and D palmar lines were impossible totrace or stopped without going anywhere. The hypothenarpatterns were usually too complex to describe by a singlepattern name, and in addition the palmar axial triradius tendedto be distal. The carriers (mothers) had some but not all ofthese patterns. The complex hypothenar patterns were presentin both mothers. The normal people in this series had none ofthese findings.Thus dermatoglyphics may prove to be another clinical

measure for diagnosis of patients with anhydrotic ectodermaldysplasia and of the carrier or less affected female.

This work was aided by a grant from the National Foundation.

JEAN H. PRIEST.

Departments of Pathology and Pediatrics,University of Colorado Medical Center,

Denver, Colorado 80220.

INSULIN AND GLUCOSE RESPONSE TO

GLUCAGON IN DOWN’S SYNDROME

SIR,-Abnormal glucose tolerance has been reported 1-3in patients with Down’s syndrome (D.S.). In children with

D.S., other mentally retarded children, and normal children,we have found that the mean rise in plasma-immunoreactive-insulin level after oral glucose is only about half that observedin adults.4 Since glucagon has been shown to promote insulinsecretion in adults,5 6 we decided to measure the response toit of these children.

16 children (aged 20 months to 6 years 4 months) werestudied: 6 had D.s., 5 were mentally retarded from othercauses, and 5 were normal. All were taking a high-carbohydratediet containing 1000-2000 calories per day. After an overnightfast 0-5 mg. glucagon was given intravenously during 1-2

1. O’Leary, W. D. Am. J. Dis. Child. 1931, 41, 544.2. Runge, G. H. Am. J. ment. Defic. 1959, 63, 822.3. Benda, C. E. The Child with Mongolism; p. 175. New York, 1960.4. Milunsky, A., Rubenstein, A. H., Lowy, C., Wright, A. D. Devl Med.

Child Neurol (in the press).5. Yalow, R. S., Black, H., Villazon, M., Berson, A. A. Diabetes, 1960,

9, 356.6. Samols, E., Marri, G., Marks, V. Lancet, 1965, ii, 415.