STIMULATING BILIRUBIN CONJUGATION

982

contaminant, and further experiments

are in hand to test what of contamination could give positive results, since such information does not seem to be generally available. Meanwhile the results are presented in the hope that they will be subjected to independent testing in units in which scrapie material is not (knowingly) handled. I should like to thank Miss Greta Joyce for assistance in all stages of this work. M.R.C. Demyelinating Diseases Research Unit, 13 Framlington Place, E. J. FIELD. Newcastle upon Tyne 2.

(known) degrees

DECREASED PROPERDIN ACTIVITY IN SWISSTYPE LYMPHOPENIC AGAMMAGLOBULINÆMIA SIR,-Several workers 12 have reported normal serum " properdin " activity in patients with agammaglobulinxmia (A.G.G.). Recent splitting of " agammaglobulinxmia " into several discrete syndromes 34 has led us to re-explore the serum-concentrations of this factor in a small group of patients with different forms of A.G.G. Properdin, measured as outlined by Todd et al.,5 represents an activity which is removed from serum by absorption with zymosan at 15—17°C, this is necessary to allow zymosaninduced inactivation of the classical third component of complement at higher temperatures.Lately properdin has been characterised as a 5S P-globulin of 223,000 molecular weight which lacks immunoglobulin antigenic determinants and the complement component activities C’lq, C’lr, C’ls, C,4, and C’2.’Results of the present study are shown in the accompanying table. In confirmation of earlier investigations, normal PROPERDIN,

C’lq,

AND

HaeMOLYTIC

GLOBULINaeMIA

*

Units per ml.’

t Agglutination units

C’

ACTIVITIES

IN

titres of complement components other than C’11° suggested that the C’lq abnormality derived from decreased synthesis. In-vitro investigations relating C’l formation to the intestine," and the regularly occurring intestinal damage in patients with A.G.G.,12 particularly pronounced in Swiss-type A.G.G.,13 suggested to us that lymphointestinal damage or abnormality might be the basis of the lowered C’lq titres; perhaps lymphointestinal alteration also relates to the decreased properdin activity in patients with Swiss-type A.G.G. H. GEWURZ Departments of Pediatrics and Microbiology, University of Minnesota Hospitals, R. J. PICKERING and Department of Medicine, G. NAFF Case Western Reserve R. A. GOOD. of Medicine. School University STIMULATING BILIRUBIN CONJUGATION SIR,-It has been shown that newborn animals of some species do not develop hyperbilirubinxmia at birth and can handle bilirubin loads better than the low level of specific transferase would suggest.14-166 This raises the question whether the low level of transferase explains human neonatal jaundice, even though it has been proved that diethylnicotinamide (a substance stimulating bilirubin-conjugating in activity in liver slices of neonatal rabbits 17) is effective lowering bilirubin levels in newborn infants.18 dit)host)hate-szlucose (U.D.P.G., ’Toxepase’, Robin S.p.A.,

Uridine-

AGAMMA-

(A.G.G.)

per 01 ml.8

t Units

per ml.9

serum-properdin activity was observed in five patients with Bruton and late-occurring types of A.G.G., despite their extreme deficiency of immunoglobulins. However, serum-properdin concentrations were strikingly decreased in two patients with lymphopenic A.G.G. of the Swiss type. In recent studies of the complement system in several A.G.G. syndromes, a somewhat similar alteration of the C’lq subcomponent of the C’l macromolecule was observed: C’lq serum-titres were strikingly reduced in Swiss-type A.G.G. and only moderately reduced in the other A.G.G. syndromes, as shown by Gewurz et al.and in the table. Normal or raised 1. Barundun, S. Das Antikorpermangelsyndrom. Basle, 1959. 2. Good, R. A., Kelly, W. D., Rotstein, J., Varco, R. L. Progr. Allerg. 1962, 6, 187. 3. Peterson, R. D. A., Cooper, M. D., Good, R. A. Am. J. Med. 1965,

38, 579. 4. Seligmann, M., Fudenberg, H. H., Good, R. A. Unpublished. 5. Todd, E. W., Pillemer, L., Lepow, I. H. J. Immun. 1959, 83, 418. 6. Pillemer, L., Blum, L., Lepow, I. H., Wurz, L., Todd, E. W. J. exp. Med. 1956, 103, 1. 7. Pensky, J., Hinz, C. F., Jr., Todd, E. W., Wedgwood, R. J., Boyer, J. T., Lepow, I. H. J. Immun. 1968, 100, 142. 8. Gewurz, H., Pickering, R. J., Christian, C. L., Snyderman, R., Mergenhagen, S. E., Good, R. A. Clin. exp. Immun. 1968, 3, 437. 9. Osler, A. G., Strauss, J. H., Mayer, M. M. Am. J. Syph. Gonorrhea vener. Dis. 1952, 36, 140.

Milan, Italy) treatment stimulates bilirubin-conjugating activity in mice infected with hepatitis,19 and induces a lower

bilirubin peak in the adult man after an intravenous bilirubin load.2O These results prompted us to investigate the effect of U.D.P.G. in human neonatal hyperbilirubinasmia. Considering the wide physiological scattering of bilirubin levels in newborn infants, twins only were investigated (all with Rh and blood groups compatible with their mothers). In most instances (6 of 9 pairs) 1 twin was treated and the other kept as a control. In 3 instances no treatment was given to either twin, to check similarity of the postnatal bilirubin serum-levels in twins. U.D.P.G. was administered intramuscularly, 2-5 mg. per kg., once a day from the first to the fifth day of life. Blood-samples 10. Gewurz, H., Pickering, R. J., Good, R. A. Int. Archs Allergy appl. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.

Immun. 1968, 33, 368. Colton, H. R., Borsos, T., Rapp, H. J. Proc. natn. Acad. Sci. U.S.A. 1966, 56, 1158. Johnson, R. C., Van Arsdel, Jr., P. P., Tobe, A. D., Ching, Y. Am. J. Med. 1967, 43, 935. Hoyer, J. R., Cooper, M. D., Gabrielsen, A. E., Good, R. A. Medicine, Baltimore (in the press). Schanker, S., Schmid, R. Proc. Soc. exp. Biol. Med. 1964, 115, 446. Odell, G. B. New Engl. J. Med. 1967, 277, 193. Odell, G. B. ibid. p. 662. Careddu, P., Piceni-Sereni, L., Giunta, A., Sereni, F. Minerva pœdiat. 1964, 55, 2559. Sereni, F., Perletti, L., Marini, A. Pediatrics, Springfield, 1967, 40, 446. Giunta, A., Apollonio, T., Livini, E. Medna int. Milano, 1967, 8bis, 10. Bernardi, R. Personal communication.

983 were obtained from venous the first, third, fifth, and seventh days of life. The results (see figure) clearly showed a lower level of bilirubin in u.D.P.G.-treated subjects from the third to the seventh day of life, while no differences were observed between members of the controlled pairs. Statistical evaluation indicated that the differences became highly significant starting from the fifth day. These data might indicate that newborn infants have a decreased amount of U.D.P.G. available for bilirubin excretion. However, previous studies showed that uridine-diphosphateglucuronic-acid can enhance the rate of glucuronidation of appropriate substrates.21 We have not yet obtained definitive data on the therapeutic value of U.D.P.G. in neonatal severe hyperbilirubinaemia, but our first impression is that U.D.P.G. has been effective in lowering bilirubin levels in some patients with severe non-haemolytic neonatal jaundice. No untoward effects have been seen after u.n.n.. administration. PAOLO CAREDDU Department of Child Health, ANTONIO MARINI. University of Milan, Italy.

for

plasma-bilirubin concentration

puncture

Obituary

at

KEITH WALDEGRAVE MONSARRAT

T.D., M.B. Edin., F.R.C.S.E. Mr. K. W. Monsarrat, surgeon to the David Lewis Northern Hospital, Liverpool, for 30 years, died on April 28 at the age of 96. He was a former dean of the faculty of medicine in the University of Liverpool. Of Huguenot descent, he was born in Kendal and was educated at King William’s Col-

lege, Isle of Man, and at King Henry VIII School, Coventry. In 1890 he enrolled at the University of Edinburgh, graduating M.B. four years later. After holding houseat appointments Nottingham General Hospital and Great Yarmouth Hospital, he took the in 1897 and in the same moved to Liverpool. He was appointed assistant surgeon to the Cancer Hospital in 1898 and in the following year assistant surgeon to the Liverpool Children’s Infirmary. In 1902 he joined the staff of the David Lewis Northern Hospital as honorary surgeon, where he remained until his retirement in 1932. Soon after his appointment to the Northern, when the University of Liverpool received its charter, Monsarrat was one of a small group of clinicians who tried to establish a closer relationship between the Liverpool hospitals and the university. As a result, the United Clinical School was formed in 1906, with direct representation of the hospital clinical staffs on the faculty of medicine. His bent for medical education was recognised by his appointment in 1907 as lecturer in clinical surgery and in 1911 as lecturer in operative surgery at the university. He was also dean of the faculty of medicine from 1908 to 1914. Monsarrat took an early interest in the Volunteer Movement, joining the 1st Volunteer Brigade of the King’s Liverpool Regiment. At the beginning of the 1914-18 war he was immediately called up and was posted to Salonika where he was in charge of the surgical division with the 37th General Hospital. He was twice mentioned in despatches and was awarded the Serbian Order of St. Sava and the Territorial Decoration. On demobilisation he resumed his surgical practice and academic work in Liverpool. As a result of the war, public subscriptions for voluntary hospitals had dwindled, and he at once realised the need for hospital reorganisation. In 1927 he took part in the negotiations which led to the formation of the Merseyside Hospitals Council. In the same year he was elected to the General Medical Council as the university’s representative, and in 1930 he was president of the Liverpool Medical Institution. He was made a life member of the institution last year. He retired in 1932, and for the next five years he wrote many philosophical articles and pamphlets on such subjects as health and the human spirit and human understanding and its world, but in 1937 he went back to medical work and he became group officer E.M.S. for Liverpool, throughout the 1939-45 war he controlled the medical services in the city. After the war he continued to take an active interest in medical affairs, and he was a member of several committees of the Ministry of Health while the National Health Service was being constructed. On his 90th birthday a group of friends compiled a book of selections from his own work as a tribute. Mr. Monsarrat is survived by a son and a daughter of his first marriage and by his second wife, Marie, widow of Dr. J. G. Adami, F.R.S., whom he married in 1947. F.R.C.S.E.

CARBOHYDRATE METABOLISM IN THE NEWBORN SIR,-I have read with interest your annotation (Feb. 17) in which you summarise recent reports on the incidence and nature of neonatal hypoglycxmia. The findings obtained by us in 194122 may be of interest in this respect. In quite a large percentage of healthy newborns of non-diabetic mothers we found after the cutting of the umbilical cord not only a symptomless hypoglycaemia (in 2 cases even 0 !), but also during the following hours and days unusually wide fluctuations of bloodsugar between frankly hypoglycaemic and diabetic values. It even appeared that the lower initial blood-sugar values had been, the higher they subsequently rose (up to 300 mg. per 100 ml.). In most cases the blood-sugar became stabilised at low normal levels at the end of the first week of life. GERDA WOLFSOHN-ZONDEK. Jerusalem, Israel.

UBIQUITOUS BLUE SPOT SIR,-In his letter (March 9, p. 536) Dr. Hoeygaard states: " It seems that the Mongolian blue spot is a plaque of dark-blue pigmentation over the inferior part of the back of newborn children in dark-complexioned people, and is not, as formerly believed, a specific sign of Down’s syndrome ". I have been unable to find any recent or classic textbook of or dermatology in which the Mongolian spot is described as a specific sign of Down’s syndrome. It is generally accepted that these spots, first described by Fabie in 1816, are microscopically blue naevi of sparse cellularity. 23 They are hereditary and transmitted according to mendelian law,24 and may be found also in 1-3% of newborn infants in Central Europe.25 Although the majority of Mongolian spots are found over the buttocks, this is by no means the only region where they can be observed, and they are even found on parts of the body where the skin is at maximal tension over a bony prominence. Mongolian spots may be found even in very small premature infants. On the other hand, they are seen in all Eskimos and Indians, as stated by Dr. Hoeygaard. Since they are known to be present in all newborn of the Mongolian race,25 and in half of Negro newborns,26 irrespective of the position of the fcetus in the uterus, it seems to me that until additional evidence is at hand, the inclusion of trauma as an aetiological factor, though interesting, should be regarded with caution. Department of Pœdiatrics, Hasharon Hospital, THEODORE IANCU. Petah Tiquah, Israel.

paediatrics

21. 22. 23. 24. 25.

Pogell, B. M., Leloire, L. F. J. biol. Chem. 1961, 236, 293. Zondek, H., Wolfsohn, G. Acta med. scand. 1941, 106, 468. Stowens, D. Pediatric Pathology; p. 796. Baltimore, 1966. Traub, E. F. Pediat. Clins N. Am. 1956, 3, 665. Siwe, S. in Lehrbuch der Pædiatrie (edited by G. Fanconi and gren); p. 844. Basle, 1956. 26. Nelson, W. E. Textbook of Pediatrics; p. 340. London, 1964.

A. Wall-

year

J. A. R. and P. H. H. write: " With Monsarrat passes a whole era of British surgery, dominated by such great names as that of Moynihan. Indeed,