McGILL UNIVERSITY

302 CHEMOTAXIS AND UMBILICAL SEPARATION

SiR,—Hayward et al.l have identified six infants from two prolonged attachment of the umbilical cord. Subsequently, severe bacterial infections developed in five. The two tested had defective neutrophil mobility. Hayward et al. suggested that a primary genetic defect of a contractile protein could explain the association. We have studied two unrelated patients with recurrent infections who may have a similar .problem. Their clinical symptoms date from the newborn period. Our patients, like Hayward’s, had difficulty with separa-

IVY BLEEDING-TIME BEFORE

AFTER A LARGE DOSE

Department of Pediatrics, School of Medicine, University of Washington, Seattle, Washington 98195, U.S.A.

TOM BOWEN HANS D. OCHS RALPH J. WEDGWOOD

ASPIRIN AND BLEEDING-TIME: DEPENDENCY OF AGE

SIR,-While O’Grady and Moncada8 and Godal et a1.9 agree that a small dose of aspirin prolongs bleeding-time, they disagree upon the effect of a large dose. This disagreement may be explained by differences in the age and sex of their volunteers as well as by differences in the small dose used. We find that the lowest dose which produces the longest bleeding-time varies greatly from person to person, but almost always is between 1 and 3.5mg/kg given orally after an overnight fast. Using the ’Simplate II’ bleeding-time device (General Diagnostics, New Jersey) we determined the Ivy bleeding-time in three groups of ten healthy male volunteers who were not tak ing any medicines, before (Bo), after 1 or 3.5mg/kg aspirin (the longr bleeding-time being B1), and after 20 mg/kg (B2) of aspirin. We cannot shorten the bleeding-time further by increasing the dose above 20 mg/kg. All the volunteers gave written informed consent to the study.

chemotaxis and cellular immunity in

a

child with recurrent infections.

Ann Intern Med 1973; 78: 515-19. 3. Hill HR, Quie PG. Raised serum-IgE levels and defective neutrophil chemotaxis in three children with eczema and recurrent bacterial infections. Lancet 1974; i: 183-87. 4. Hill HR, Ochs HD, Quie PG et al. Defect in neutrophil granulocyte chemotaxis in Job’s syndrome of recurrent "cold" staphylococcal abscesses. Lancet 1974; ii: 617-19. 5. Pincus SH, Thomas IT, Clark RA, Ochs HD. Defective neutrophil chemotaxis with variant ichthyosis, hyperimmunoglobulinemia E, and recurrent

infections. J Pediatr 1975; 87: 908-11. 6. Bowen T, Ochs HD, Rosen H et al. Severe recurrent bacterial infections and lack of granulocyte adherence and chemotaxis. Clin Res 1979; 27: 82A. 7. Fontan G, Lorente F, Rodriguez MC, Ojeda JA. Granulocyte adherence in

umbilical cord blood. J Pediat 1979; 94: 969-70. 8. O’Grady J, Moncada S. Aspirin: a paradoxical effect

on

bleeding-time.

Lancet 1978; ii: 780. 9. Godal HC, Eika C, Dybdahl JH, Daae L, Larsen S. Aspirin and bleedingtime. Lancet 1979; i: 1236.

10

In all age-groups the

bleeding-time on a low dose of aspirin (BB,,) (p <0.001), but only in group I (p <0.01) and in group III (p <0.025) was there a significant decrease in bleeding-time when the aspirin dose was increased to 20 mg/kg (BI-Bz) (paired t test) (table). Bo was significantly shorter in group 11 than in group i (p <0.05) indicating that bleedingtime decreases with age in men. Since there was no significant difference in B2 in all three groups, this indicates that proaggregatory prostaglandins (thromboxane, TXA2) dominate over antiaggregatory prostaglandins (prostacyclin, PGIz) more in

increased

elderly than they do in younger men. The ratio (B2-Bo)/B! should correlate to the sum of the effect of thromboxanes and prostacyclins on the Ivy bleeding-time, being positive when thromboxanes dominate, zero when they balance, and negative when prostacyclins dominate. This ratio was significantly lower in groupi and group 11 than in group III (p
higher

_

-

KAJ ANKER JORGENSEN

Coagulation Laboratory, Aalborg Hospital, DK-9100 Aalborg, Denmark

ANDERS SCHOU OLESEN JORN DYERBERG ERIK STOFFERSEN

McGILL UNIVERSITY

1.

Hayward AR, Leonard J, Wood CBS, Harvey BAM, Greenwood C, Soothill JF. Delayed separation of the umbilical cord, widespread infections, and defective neutrophil mobility. Lancet 1979; i: 1099-01. 2. Clark RA, Root RK, Kimball HR, Kirkpatrick CH. Defective neutrophil

(BO)’ AFTER A SMALL DOSE (Bl)’ AND

OF ASPIRIN IN THREE GROUPS OF

HEALTHY MALE VOLUNTEERS

families with

tion of the umbilical cord. In one the cord did not detach for 2-3 weeks. In the second patient omphalitis developed at 5 days; it responded poorly to therapy and the umbilicus had to be excised. Neither family has a history of increased infections or delayed separation of the umbilical cord. Both patients had severe defects of neutrophil and monocyte chemotaxis. The most striking abnormality was failure of their leucocytes to adhere in the normal fashion to glass or plastic surfaces or to nylon wool. Unlike other syndromes with chemotactic defects,2-5 neither patient has raised IgE values. (Some details of one patient were published6 earlier this year and further details of both will be reported elsewhere.) Have Hayward et al. or others studied neutrophil and monocyte adherence in these patients? Normal neonates have normal adherence.’ If defective adherence is a general characteristic of this syndrome it is sufficiently striking to provide a simple laboratory means for the early identification of affected infants.

(B2)

on

SiR,-Your Round the World column (June 30, p. 135) language legislation and social change in the Province of

Quebec and

their possible effects on McGill University conand some comments that may be misinterpreted. Throughout its history, McGill has enjoyed many advantages from its location in Montreal, one of the oldest cities in North America and, with its predominantly French-speaking population, one of the most distinctive. The city lends an important element to the lives of the McGill community. However, neither the Provincial Government nor any other source has pressured McGill to become a bilingual or unilingual ,French-speaking institution. A Province such as Quebec needs both French and English institutions of higher learning. The majority of the population also perceives the need for a university of international reputation, such as McGill, that will provide access to and the outlook of comparable institutions throughout North America." tains

errors

303

Contrary to

some

predictions (and

in contrast

to most

other

Canadian universities) McGill’s 1978-79 enrolment increased

slightly over the previous year. In the first-year medical class 110 Quebec residents, 20 Canadians there are from other Provinces, 25 Americans, and 5 students from other parts of the world. Clearly the McGill Faculty of Medicine is maintaining its international flavour. We believe that we have the resources to keep up our international reputation as a centre of higher learning in the biomedical sciences, and to make a major contribution to the social aspects of health care in the Province. I disagree with your correspondent’s implied view that these objectives are mutually exclusive. The cutbacks in out-of-Province residents and interns at Quebec universities proposed by the Quebec Ministry of Social Affairs (Health) would have had the greatest effect on McGill, since our Faculty accepts about 200 out-of-Province residents and interns each year. As a result of media coverage of McGill’s position and with full support from the faculties of medicine in the Province, the Ministry agreed that there would be no limitation on the number of out-of-Province residents or interns entering training programmes at McGill or any other Quebec university. Other Canadian provinces have expressed similar intentions to reserve resident and intern posts primarily for their own medical graduates. Following the lead taken by McGill, briefs will be presented to government authorities across Canada, so that the free movement of residents and interns between provinces can be maintained, to the advantage of the trainees and the populations they will serve. The opinion that greater efforts on the part of McGill to obtain integration with the community around us will lead to a reduction in donations from graduates and others elsewhere in Canada is not substantiated by recent experience. In a development campaign that ended in May, 1979, McGill received $27.2 million, the largest amount ever raised by a Canadian university and$2 million in excess of the target. Annual giving by alumni, in addition to the development campaign, for the fiscal year ending May 31, 1979, was substantially increased over the previous year. Over the past eighteen months the Faculty of Medicine has established the McGill Cancer Centre, the Centre for Human Genetics, the W. L. Kellogg Centre for Advanced Studies in Primary Care, and the Shriner’s Research Laboratories for Childhood Arthritis, all supported

approximately

by substantial new endowment funds. McGill’s operating deficit last year was$1.48 million (not $2.7 million) and it was anticipated in the budget. Restrictions on operating funds are not peculiar to McGill nor to the Province of Quebec. There are more French-speaking students at McGill than formerly and McGill has indeed developed closer working relations with her sister universities in Quebec, but it is quite erroneous to suggest that the general feeling at McGill is anything but appreciative of the broadening of the university’s base in its immediate society. We feel optimistic that McGill University will be able to meet the challenge of language legislation and other challenges of the future. This prediction seems all the more certain when one looks back on the past 150 years of achievement of McGill University and its Faculty of Medicine. Faculty of Medicine, McGill University, Montreal, Quebec, Canada

S.O. FREEDMAN Dean

PASSIVE TRANSFER IN DIABETES MELLITUS

SIR,-Lipsick et al.l and Thurneyssen et al. were unable to produce hyperglycaemia in athymic nude mice after transfer of 1.

2.

Lipsick J, Beattie G,

Osler AG, Kaplan NO. Passive transfer of lymphocytes from diabetic man to athymic mouse. Lancet 1979; i: 1290-91. Thurneyssen O, Jansen FK, Vialettes B, Vague PH, Selam JL, Mirouze J. Passive transfer of lymphocytes from diabetic man to athymic mouse. Lancet 1979; i: 1291-92.

peripheral blood lymphocytes from patients with insulindependent diabetes mellitus-in contrast to findings in our laboratory.3 Passive transfer of hyperglycaemia to mice is not possible in all cases in our hands either. So far we have attempted passive transfer of diabetes mellitus from 27 patients to athymic nude mice and/or normal-haired mice (BALB/c). Among these 27 groups of recipient mice--each comprising of at least five mice at the onset of the experiment-five groups showed a mean blood-glucose value of more than 200 mg/dl (1 mg/dl=0056 mmol/1) at one or more measurements. Seven groups showed peak mean blood-glucose values between 150 and 200 mg/dl. Three groups with values under 150 mg/dl had at least two glucose values significantly higher than those in simultaneously investigated control mice, which in no group exceeded a mean of 130 mg/dl. Finally there were 12 groups which did not fulfil any of the mentioned criteria-i.e., passive transfer from the corresponding 12 patients

possible. Lipsick et al.’ suggest viral transfer as an explanation for our findings. This possibility is supported by the fact that streptozotocin diabetes (multiple dosage) can be transferred from mouse to mouse by both alive and dead lymphocytes.4 Further, mice may acquire hyperglycaemia after inoculation of a proven human diabetogenic virus.s We are now studying virus transfer as a possible aetiological agent in our model. Serra et awl. report unsuccessful passive transfer of streptowas not

zotocin diabetes from rat to rat. The donor rats were made diabetic with single dosage streptozotocin. There is no evidence for involvement of the immune system in the diabetogenesis after a single dosage of streptozotocin,7 which is probably purely a beta-cell toxin.8 Successful passive transfer would not be expected in this context, and the negative result of’Serra et al. cannot be used as an argument against other passive transfer models. Passive transfer of hyperglycaemia has been done in different animal models by different investigators.9 Clarification of the mechanism seems to be essential.

Pathological-Anatomical Institute, Kommunehospitalet, DK-1399 Copenhagen K, Denmark Hvidøre Hospital, Klampenborg

K. BUSCHARD J. RYGAARD STEN MADSBAD

PRENATAL DIAGNOSIS OF CONGENITAL ADRENAL HYPERPLASIA a letter1 and a paper2 appeared in The Lanthe use of HLA typing of cells obtained by amniocentesis in the prenatal diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Although these studies have significantly enriched our knowledge of the causes of this disorder, the utilisation of the technology of

SIR,-Recently

cet

describing

3. Buschard K, Madsbad S, Rygaard J. Passive transfer of diabetes mellitus from man to mouse. Lancet 1978; i: 908-10. 4. Kiesel V, Kolb H, Freytag G. Streptozotocin-induced diabetes: a transmissible disease. Diabetologia 1978; 14: 245. 5. Yoon JW, Austin M, Onodera T, Notkins AL. Virus-induced diabetes mellitus. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. New Engl J Med 1979; 300: 1173-79. 6. Sitges Serra A, Farndon JR, Shenton BK, Johnston IDA. Passive transfer of lymphocytes from diabetic man to athymic mouse. Lancet 1979; i: 1292. 7. Rossini AA, Williams RM, Appel MC, Like AA. Complete protection from low-dose streptozotocin induced diabetes mellitus. Nature 1978; 276: 182-84. 8. Rerup CC. Drugs producing diabetes through damage of insulin secreting cells. Pharmacol Rev 1970; 22: 485-518. 9. Buschard K, Rygaard J, Madsbad S. Etiology of insulin-dependent diabetes.

New Engl J Med 1979; 300: 924-25. 1. Couillin P, Nicolas H, Boué J, Boué A. HLA typing of amniotic-fluid cells applied to prenatal diagnosis of congenital adrenal hyperplasia. Lancet 1979; i: 1076. 2. Pollack

MS, Levine LS, Pang S, Owens RP, Nitowsky HM, Maurer D, New MI, Duchon M, Merkatz IR, Sachs G, Dupont B. Prenatal diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency) by ing. Lancet 1979; i: 1107-08.

HLA typ-