982

response. Thalidomide has been proved to be a folic-acidantagonist (like methotrexate),21 and a riboflavine antagonistand aglutamic-acid antagonist in its relation with y-aminobutyricacid (G.A.B.A.).22

Considering both the contradictory results of the effects ofthalidomide on homograft reactions found by Dr. Floersheim(Jan. 22) and my own experiments, I think that the immuno-suppressive effect of thalidomide ought to be further studied.Investigations in this field, using other hypersensitivityreactions, are being done by my co-workers and myself.

I am indebted to Dr. M. Timar, Dr. D. Winter, and Dr. F.Strugurescu for kindly supplying the thalidomide I used, and toMrs. E. Demien for technical assistance.

ADRIAN VLADUTIU.

Department ofPathological Physiology,Institute of Medicine,

Bucharest 8.

GLANDULAR FEVER AND COLD AGGLUTININS

SIR,-Glandular fever is rarely associated with hsmolyticansemia, and, moreover, the serology is very variable. I amunaware of a recorded association with the cold-heemag-glutinin syndrome, and in the case I report here the antibodypossessed some unusual properties.A young man complained of lethargy, and of painful hands

and nose-tip while motor-cycling to work. He was found tohave generalised lymphadenopathy, and a Paul-Bunnell testwas positive-1/640 with guineapig-kidney adsorbed serum,and 1/10 with ox-cell adsorbed serum. Referred to this

laboratory for investigation of " ? cold agglutinins " he wasfound to have, additionally, faint icterus and hepato-splenomegaly.Laboratory InvestigationsHb 11 -1 g. per 100 ml. Total white blood-cells 9400 per c.mm.,

with 12’’<, " glandular-fever cells ". Reticulocytes 5-4%.Haptoglobins absent. Osmotic fragility normal. Serum-bilirubin 1-6 mg. per 100 ml. No L.E. cells. Wassermannreaction negative. The direct Coombs test was negative with awide variety of antihuman-globulin sera in serial dilutions,and when an albumin-washing technique was used. Theindirect Coombs test was also constantly negative, though thepH and complement content were varied and enzyme-pre-modified cells were used.The serum contained cold agglutinins. These were active

against all of several hundred cells used, including cord,Martin, Oi, and Bombay cells. There were no negative-reactingcells, and all reacted to very nearly the same degree. An averagetitre was 1/20,480 at 2 C, 1/1280 at room temperature, and1/10 at 30CC. There was little difference in titre between the

panel cells and the patient’s own cells. The titrations tended toshow a " zone " of 2 or 3 tubes which was maximal at hightemperatures and disappeared at 4&deg;C, and was also abolished byperforming the tests in serum-albumin and by lowering the pH.No inhibition was obtained with secretor and non-secretorsalivas of all ABO groups, nor with hydatid-cyst fluid. Aggluti-nation was strikingly inhibited by enzymes (ficin and papain),only weak reactions being obtained at a dilution of 1/1 withenzyme-premodified cells. The antibody was notably sensitiveto changes in pH-e.g., at 12&deg;C and pH 5 the titre was 1/10,240at pH 7-2 1/160, and at pH 9 only 1/20.Attempts to induce hxmolysis in vitro were uniformly

unsuccessful despite varying the pH and complement content,and using enzyme-premodified cells. This was somewhat

unexpected, for on one occasion the patient’s blood, taken intoacid-citrate-dextrose solution, underwent massive spontaneoushxmolysis within a few minutes. The Donath-Landsteinertest was negative.There appeared to be no overlap between cold agglutinins

and heterophile antibodies: the former could be adsorbed outwithout influencing the titre of the latter.

21. Kempner, F. Z. ges. exp. Med. 1961, 135, 454.22. Leck, J. M., Miller, F. L. M. Br. med. J. 1962, ii, 16

Red-cell Survival

By the 51Cr method, mean red-cell life (37% survival) was34 days. Spleen: liver ratio was maximal (3-1) on the 28th day.ProgressThe Paul-Bunnell test was negative in 6 months. The cold-

agglutinin titre remained raised for nearly a year.I am indebted to Dr. G. Sackstein for referring the case to me, and

to Dr. H. G. Koster (Regional Blood Transfusion Centre, Brentwood)for much of the serologv.

A. J. BRAFIELD.Whipps Cross Hoapital,

London E.11.

SUXAMETHONIUM AND UTERINE ACTIVITY

J. SELWYN CRAWFORD.

Research Department of An&aelig;sthetics,Royal College of Surgeons of England,

Lincoln’s Inn Fields,London W.C.2.

SIR,-Perhaps Dr. Felton and Mr. Goddard (April 16) maybe encouraged to extend their observations to include measure-ment of the extent to which uterine activity is influenced bysuxamethonium given by infusion in the range of dosage usedclinically. I strongly suspect that the response to which theyhave drawn attention comes into the category of the " slug ofdrug " effect ’1 2 and will not be measurable when a similarlyadequate degree of muscle relaxation is induced by an infusionof the drug.

It would also be of interest to know whether a reasonabledose of atropine (say 1-0 mg. intravenously) will block theresponse of the uterus to suxamethonium.

EXCHANGE TRANSFUSION IN HEPATIC COMA

SIR,-I am prompted by your leading article (March 26) todescribe briefly the case of a little girl who, when aged 4112years, fully recovered from hepatic coma after an exchangetransfusion, carried out at a stage in her illness when theoutlook seemed utterly hopeless.The patient, who was born on Dec. 17, 1959, was admitted

to this hospital on July 30, 1964, because of deepeningjaundice, increasing abdominal pain, and the recent develop-ment of screaming attacks. 5 weeks before admission her

general practitioner consulted me because of the patient’sabdominal pain, pale stools, and dark urine. Although shewas not jaundiced, anicteric infective hepatitis was provisionallydiagnosed because of a widespread local outbreak and knowncontact with two affected children. After a week she became

symptom-free, but a few days later abdominal pain alonerecurred, and slowly increased in intensity until her admission.3 weeks after the onset of her illness jaundice was first noticed,and vomiting started and became a troublesome feature. Onceagain her stools became clay-coloured and her urine yellow-brown. On the day of admission she started having screamingepisodes when she would roll around the bed and bang herhead against the wall. Between these violent outbursts sheseemed delirious.On admission, the patient was cooperative, and complained

bitterly of abdominal pain. She was afebrile, pulse 120 perminute, deeply jaundiced, and with liver enlarged, firm,smooth, and slightly tender. Hb 80%, mild hypochromia ofred blood-cells, white blood-cells 12,000 per c.mm. (neutro-phils 62 %); erythrocyte-sedimentation rate (E.S.R.) 1 mm. in1st hour. Urine: heavily bile-stained, with urobilinogen inexcess. Liver-function tests: serum-bilirubin (per 100 ml.),total 23-4 mg. (direct 16-6 mg., indirect 6-8 mg.); serum-alkaline-phosphatase, 23-7 King-Armstrong units; thymolturbidity, 5 units; thymol flocculation, -)- +, zinc sulphate,4 units; serum-proteins (per 100 ml.), 5-3 g. (albumin 3-2 g.,globulin 2-1 g.).Clinical Course and Treatment

During the first 10 days in hospital (i.e., until exchange1. Paton, W. D. M. Proc. R. Soc. Med. 1960, 53, 815.2. Crawford, J. S. Br. J. An&oelig;sth. (in the press).

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SERUM-BILIRUBIN BEFORE AND AFTER EXCHANGE TRANSFUSION

transfusion) the patient complained from time to time ofabdominal pain, was reluctant to take food, vomited 2 or 3times a day, and remained deeply jaundiced (see accompanyingtable). On her 8th day in hospital erythema of palms wasfirst noticed and a spider naevus appeared on the right arm.By this time her liver was getting smaller. The following daybruising was first noticed, associated with a low prothrombinlevel.

During the first week in the ward the patient’s mental statevaried greatly. Alertness and lucidity fluctuated withdrowsiness and confusion. At times she would be restless,disorientated, and talk irrationally. Between the 7th and 10thdays in hospital her mental state deteriorated further. Formost of the time she was restless, confused, inaccessible, andhallucinated. Insomnia became troublesome. On the 9th daya low-protein diet was introduced, and neomycin (2 g. daily)and prednisone (40 mg. daily) were commenced.On the 10th day in hospital the patient became comatose,

although at times she would respond to painful stimuli. Shestarted to have violent attacks of screaming which could beheard around the hospital and for some distance outside. Theclinical picture, by now, was of acute mania. She developedfoetor hepatis and her shrinking liver was difficult to palpate.At this juncture her total serum-bilirubin concentration was39-5 mg. per 100 ml., and the free pigment had risen rapidlyfrom 8 to 24-5 mg. per 100 ml. in 48 hours (see table), associatedwith a reticulocytosis of 5-5% and a falling hxmoglobin-suggesting the development of a mild hsemolytic stated 1

Reticulocytosis persisted and reached a value of 7-5% 31/2weeks after admission.On the llth day in hospital, because of the patient’s des-

perate plight and the high level of free bilirubin, an exchangetransfusion was carried out through the right femoral vein;in all 2050 ml. of blood was removed and 2040 ml. of freshblood was injected, the whole procedure taking 3 hours. Atthe end of the transfusion the serum-bilirubin level was6-4 mg. per 100 ml. (free pigment 0-3 mg. per 100 ml.).During the next 9 days her serum-bilirubin rose to a level of20-5 mg. per 100 ml. (free pigment 5 mg. per 100 ml.), butthereafter steadily declined.

After the exchange transfusion the child’s mental state

improved dramatically. She became lucid and cooperativeand remained so thereafter. Her abdominal pain recededrapidly. She now showed tremor of the hands, usually fine butat times coarse, which was associated with titubation of thehead. These abnormal movements persisted for 3 weeks andthen disappeared. In the week after the exchange transfusionshe developed increasing generalised oedema and ascites whichwas attributed to hypoalbuminsemia (plasma-albumin was2-3 g. per 100 ml. 2 weeks after admission), and also to thepossible development of portal hypertension. Her severe

fluid retention responded well to two 5-day courses ofdiuretics (chlorothiazide and spironolactone).Glycosuria was noticed 48 hours after the exchange trans-

fusion and persisted for 3 weeks (1-2% each day by‘Clinitest’), associated on one occasion with hyperglycaemia(blood-glucose 320 mg. per 100 ml.). At this time she wasreceiving a liberal glucose intake, and her mellituria was

1. Conrad, M. E., Schwartz, F. D. Am. J. Med. 1964, 37, 789.

thought to reflect impaired ability on the part of the liver tometabolise this and other carbohydrates.As soon as her oedema and ascites cleared the child’s progress

to recovery was rapid and uneventful. Her various drugs wereslowly withdrawn. She was discharged fit on Sept. 18, 1964(i.e., 7 weeks after her admission), on a small dose of prednisonewhich was discontinued a few days later.

Subsequent ProgressThe child has enjoyed perfect health over the past 20 months.

She has had no hsematemeses, and her nutrition has beensatisfactory. Her liver has been normal in size and texture, andher spleen impalpable. There has been no clinical evidence ofportal obstruction. Investigations in April, 1966, have shown:Hb 86%; normal white blood-cell count; E.S.R. 5 mm. in lsthour; and liver function tests: serum-bilirubin, 0-4 mg. per100 ml.; serum-proteins (per 100 ml.), 6-8 g. (albumin 5-2 g.,globulin 1-6 g.); thymol turbidity, 2 units; thymol flocculation,+ : and zinc sulohate. 3 units.

TREVOR P. MANN.Royal Alexander Hospital for Sick Children,Brighton 1, Sussex.

EXCHANGE-TRANSFUSION APPARATUS

J. M. IBRAHIM.Queen Elizabeth Hospital for Children,

London E.2.

SiR,&nacute;The mounting of the disposable exchange-transfusionapparatus 1 on a base plate as described by Dr. Simmons andDr. Ata (April 2) does not, in my opinion, eliminate thedifficulties encountered in the procedure. In addition to the

disadvantages, which they rightly mentioned, of the disposableset (sticking of the syringe and flexibility of the two-way tapswhen joined together) I found that the handles of the tapsoften snapped half-way through the operation, necessitatingon occasions replacing the set.

I find it easier to use a transfusion set with a graduated chamberintercepting the flow of blood from the reservoir to an ordinarytwo-way tap, one end of which is attached to the umbilical-vein catheter and the other to a 20 ml. syringe. The disposablerecipient set for infants, made by Capon Heaton & Co. Ltd.,is very suitable. After a measured amount of the donor blood

goes in, the tap is turned to connect the syringe with theumbilical catheter for withdrawal, automatically cutting off theflow of the donor blood, and giving time for an assistant torefill the chamber.

Besides its cheapness, ever-availability, and simplicity, theadvantages of this apparatus are: (a) the syringe only withdrawsblood from the patient, and hence the danger of infection islessened; (b) blood is transfused into the baby by the force ofgravity and the speed of transfusion can be easily regulated;and (c) the dead space is negligible and not more than thevolume of the umbilical catheter. The only disadvantage-that of having to disengage the syringe after every withdrawal-can be obviated by inserting a second tap, leading to waste,between the first one and the syringe.

CAUSES OF STOKES-ADAMS ATTACKS

SIR,-A female patient, aged 72 years, with complete heart-block, and Stokes-Adams attacks due to episodes of ventricularfibrillation, was treated by external pacemaking for 2 days. Thispacemaking, which was strong enough to evoke electrocardio-graphic complexes but not mechanical ventricular contractionssufficient to produce clinically detectable pulse-volume, wasable to prevent attacks of ventricular fibrillation for many hours.On several occasions within a few minutes of stopping externalpacemaking ventricular fibrillation recurred; the patient couldnot be resuscitated from the last of these episodes.Many of the attacks of ventricular fibrillation had no pre-

ceding period of ventricular asystole. This suggested that, ina patient with heart-block who is not on any drug therapy,ventricular fibrillation is not necessarily a result or complica-tion of ventricular asystole. Similar mechanisms may be

1. Prosser, R. Lancet, 1963, ii, 337.