INCREASE OF SERUM ANDROGENS DURING DIAZOXIDE TREATMENT

1044

recipients. In an analysis of factors associated with CMV infection after BMT, we found that the actuarial 1-year incidence of CMV infection in recipients who were CMV seropositive before BMT was 87%, compared with 35% in recipients who were CMV seronegative (log rank test on survival curves, p<0-0001). Recipients of bone marrow from CMV-seropositive donors also have a higher incidence of CMV infections than recipients with CMV-seronegative donors (p<0 - 026). Thus in most patients CMV is either reactivated or transferred with the donor marrow cells. However, when the donors were CMV seropositive, CMVseronegative (logrank test on survival curves, p<00001). infections of 25%, compared with an 88% incidence in CMVseropositive recipients (p<0’ 03). Therefore all CMV-seronegative patients may benefit from having blood products from CMVseronegative donors even if those with a CMV-seropositive marrow donor have an increased risk of acquiring CMV infection. 38 of our 100 consecutive BMT recipients were CMV seronegative before BMT, but only 24 of those had CMV-seronegative marrow donors. Among 14 CMV-seronegative patients who received transplants from CMV-seronegative donors before March, 1983, and who received blood products from donors not screened for CMV antibodies, CMV infection developed in 3. Since March, 1983, all our CMV-seronegative BMT recipients with a CMV-seronegative donor have received blood products from CMV-seronegative donors. Among 10 such treated patients CMV infection has developed in only 1. However, this patient had received blood Influence of pretransplant transfusions —’—’—’

=

retrospective study;

on

renal

———————

allograft survival. prospective study.

unfortunate that they included living (related?) graft donors. This may have introduced a serious confounding factor. We suggest that actuarial life-table techniques and the logrank test are more appropriate than the test Bu6ifi et al used. Furthermore, their survival estimates have large standard errors because of the small number of cases. A policy of giving a limited number of pretransplant blood transfusions to end-stage renal disease patients awaiting a kidney transplant should not be changed. The beneficial effect of that policy has recently been confirmed in the report of the International 3

Transplant Study. Eurotransplant Foundation, Department of Immunohaematology/Bloodbank, University Hospital, 2333 AA

Leiden, Netherlands

G. G. PERSIJN J. D’AMARO J. J. VAN ROOD

Persijn GG, Cohen B, Lansbergen Q, van Rood JJ. Retrospective studies on the effect of blood transfusions in renal transplantation in the Netherlands Transplantation 1978; 28: 396-401. 2. Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II: Analysis and examples. Br J Cancer 1977; 35: 1-39. 3. Opelz G. Ninth International Histocompatibility Workshop Renal Transplant Study. Histocompatibility testing 1984 (in press). 1

CYTOMEGALOVIRUS ANTIBODY SCREENING OF BLOOD DONORS FOR IMMUNOCOMPROMISED SERONEGATIVE PATIENTS

SlR,-A letter in your issue of Aug 4 (p 294) reported that a solid-

enzyme-linked immunosorbent assay (ELISA) for detection of cytomegalovirus (CMV) antibodies was more sensitive and specific than other tests, such as the complement fixation test. We agree; we use the ELISA technique routinely for screening blood donors, bone-marrow donors, and patients in our bone-marrow transplantation (BMT) programme. However, individuals who have CMV IgG4 only are not always detected by such screening. In our experience around 10% of CMV-seronegative individuals have IgG4 antibodies. After transplantation we regularly screen our patients for CMV antibodies by ELISA and attempt to isolate virus from blood, bone marrow, and urine for diagnosis of CMV state

infections. Kurtz and Barlow also mentioned the importance of excluding material from CMV-seropositive blood donors for transplant

products from unscreened donors before transplantation, during treatment for leukaemia. It may therefore be desirable to screen blood products for CMV antibodies not only for BMT patients, but for all CMV-seronegative patients, mainly children, who are immunocompromised by their disease or treatment. By such blood donor screening the morbidity and mortality of CMV infection may be reduced in all immunocompromised patients. O. RINGDEN Departments of Transplantation Surgery, Clinical Immunology, and Medicine, T. PAULIN Karolinska Institute, Huddinge Hospital, P. PIHLSTEDT S-141 86 Huddinge, Sweden; B. LÖNNQVIST and Blood Bank, Karolinska Hospital, National Bacteriological Laboratory, Stockholm B. WAHREN

INCREASE OF SERUM ANDROGENS DURING DIAZOXIDE TREATMENT

SIR,-Hirsutism is a common side-effect of diazoxide treatment!,2 cause is not known. 1,3,4 We have noted increased serum androgen levels in a woman prescribed diazoxide. This 38-year-old woman had a subtotal pancreatectomy on the suspicion of insulinoma in November, 1982. Histological examination revealed diffuse B cell hyperplasia of the islets of Langerhans. Postoperatively hypoglycaemia persisted and in February, 1983, diazoxide (’Proglicem’) 250 mg daily was instituted. Blood glucose levels became normal and her symptoms of hypoglycaemia disappeared. After 2 months on diazoxide she had clear hirsutism, especially on the upper lip and arms. The hirsutism thereafter remained unchanged and there are no signs of virilism. Menstruation is regular and the patient is in good condition on continuous diazoxide therapy. Before diazoxide was given the serum level of androstenedione was slightly raised whereas testosterone, dehydroepiandrosterone

but its

SERUM ANDROGENS IN FEMALE PATIENT BEFORE AND DURING

DIAZOXIDE TREATMENT

*T=testosterone (reference range 0- 3, nmol/1); AD=androstenedione (1’0-S 0 nmol/1); DHAS=dehydroeptandrosterone sulphate (1-0-12-0 pmol/1); SHBG=sex hormone binding globulin (1’ 6-7’ 0 mg/1). tDecember, 1982. August and December, 1983 (dose 250 mg daily) and March and June, 1984 (200 mg)

1045

sulphate (DHAS), and sex hormone binding globulin (SHBG) levels normal. After diazoxide was started androgen levels, especially DHAS, rose while the SHBG level decreased (table). Because the patient is prone to hypoglycaemia it has not been possible to were

interrupt her diazoxide medication, even for a short time. Urinary excretion of 17-hydroxysteroids, 17-ketosteroids,5,6 and testosterone glucuronidé is normal during diazoxide treatment, and it has been suggested that the stimulation of hair growth could be a specific property of the drug.3,5 Our data indicate that an increase of the serum androgens could be one mechanism for diazoxide-induced hirsutism. Department of Endocrinology, Lund University Clinics, General Hospital, S-214 01 Malmö, Sweden

BENGT HALLENGREN BERNT HÖKFELT

J Diazoxide and the treatment of hypoglycemia: an historical review Ann NY Acad Sci 1968, 150: 194-203. 2 Frerichs H, Track NS. Pharmacotherapy of hormone-secreting tumours. Clin Gastroenterol 1974; 3: 721-32. 3 Burton JL, Schutt WH, Caldwell IW. Hypertrichosis due to diazoxide. Br J Dermatol 1975, 93: 707-11. 4. Parker LN, Lifrak ET, Odell WD. Lack of a gonadal or adrenal androgenic mechanism for the hypertrichosis produced by diazoxide, phenytoin and minoxidil. Biochem Pharmacol 1982; 31: 1948-50. 5 Koblenzer PJ, Baker L. Hypertrichosis lanuginosa associated with diazoxide therapy in prepubertal children: a clinicopathologic study. Ann NY Acad Sci 1968; 150: 373-82. 6. Wegienka LC, Simpson RG, Karam JH, Forsham PH Clinical experience with diazoxide. Ann NY Acad Sci 1968; 150: 383-94

a third fluid compartment and hypovolaemia. This local effect of cetrimonium bromide intraperitoneally is well known, and the quick recovery in this case does not warrant use of the term chemical peritonitis. The total duration of the reaction in this case (12 h) corresponds well with the kinetics of cetrimonium bromide. This complication, though rare, suggests the need to monitor blood pH after operations on hydatid cysts especially when large quantities of cetrimonium bromide have been used. If acidosis develops, measurement of plasma bromide levels may provide proof of the pathophysiology we suggest. P. MOMBLANO B. PRADERE N. JARRIGE General and Gastrointestinal Surgery Service, D. CONCINA CHU Toulouse-Purpan, 31059 Toulouse, France E. BLOOM

creating

1 Black

METABOLIC ACIDOSIS INDUCED BY CETRIMONIUM BROMIDE

SIR,-Cetrimonium bromide (’Cetavlon’) is widely used to sterilise hydatid cysts during surgery. Methaemoglobinaemia and chemical peritonitis have been reported after this procedure,1,2 but not severe metabolic acidosis without peritonitis. A 44-year-old man was operated on for multiple, disseminated, intra-abdominal hydatid cysts (in the liver, spleen, pelvis, abdominal wall and the peritoneal cavity). His preoperative status was otherwise normal. 1% cetrimonium bromide in sterile water was instilled into all cysts and more than a litre of washout solution was necessary. Two large hepatic cysts were partly resected. Haemodynamic status and pH and blood gas measurements remained normal during surgery. the first After postoperative hour, despite normal haemodynamics and consciousness, blood gas measurements revealed metabolic acidosis (pH 7-30, PaC02 34 mm Hg, bicarbonate 16 mmol/1, base excess -9 mmol/1). 5 h later acidosis remained unchanged despite alkali loading (sodium bicarbonate 250 mmol). Renal function and blood pressure were normal at that time. During the eighth hour, the patient experienced vasoplegic collapse (systolic blood pressure 60 mm Hg) with low central venous pressure, oligoanuria, abdominal tension, and persistent hypochloraemic acidosis (base excess -11, chloride 88 mmol/1), hyperkalaemia (7- 5 mmol/1), and increased anion gap (43 mmol/1). There was no ketosis; blood glucose was normal. Sustained alkalinisation and fluid loading led to rapid recovery. Acid-base status was normal 3 h later and remained so. Renal function rapidly returned to normal as hypokalaemia appeared (3’ 2 mmol/1). Blood cultures remained sterile and further progress was unremarkable. We suggest that this postoperative complication was caused by resorption, by cyst walls and peritoneum, of the large amount of cetrimonium bromide instilled (pH 6). Toxicity of ethanol, contained as a vehicle in the solution, can be excluded because there was only 5 g in 1 litre of the final solution and the patient had no neurological symptoms. The patient’s spontaneous favourable course after a few hours makes lacticacidosis unlikely. The chemical structure of cetrimonium bromide may provide an explanation. Bromide anion reabsorption may directly lower plasma bicarbonate levels and increase the anion gap, since the quaternary ammonium cation may enter the red blood cells, leading to transfer hyperkalaemia, worsened by metabolic acidosis itself. The late cardiovascular collapse was probably due to the prolonged duration of the acidosis and to the peritoneal exudation,

1. Baraka

al. Cetrimide induced methaemoglobinaemia after surgical excision of Lancet 1980; ii: 88-89 2. Gilchrist DS Chemical peritonitis after cetrimide wash out in hydatid cyst surgery. Lancet 1979, ii: 1374.

A,

et

hydatid cysts.

AUTOIMMUNITY AND IDIOTYPES

SIR,-The hypothesis of Dr Cooke and colleagues (Sept 29, p 723) also has relevance to therapy. In one of our patients treated with multiple doses of radiolabelled antibody, anti-antibodies have developed not only to all of the known species (rabbit, pig, monkey) from which the treatment antibodies were derived, but also to immunoglobulins that she has not been exposed to. The common element in the treatment was the Fab end of the molecules. The patient, who has a primary liver tumour, continues in remission with further improvement two and a half years after the initiation of therapy and more than a year after the end of treatment. The observations of Sears et al, with non-labelled antibody, and our observations with iodine-131-labelled antibodies2(and own unpublished) suggest that antibody against anti-idiotype may well recognise tumour antigens and modify the course of malignant disease. Oncology Center, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, Maryland 21205, USA

STANLEY E. ORDER

1. Sears

HF, Herlyn D, Steplewski Z, Koprowski H Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma. J Biol Response

Mod 1984, 3: 138-50. 2. Order SE, Klein JL, Leichner PK, et al. Radiolabelled antibodies in the treatment of primary liver malignancies. In Levin B, Riddell R, eds. Gastrointestinal cancer. Amsterdam: Elsevier, 1984: 222-32.

HOUSEHOLD CLING FILM IN CENTRAL VENOUS CATHETERISATION

SIR,-The introduction of a venous catheter requires a sterile covering of the puncture site, especially when the Seldinger guidewire technique is used. Such covers conceal anatomical reference points, and this may make the puncture more difficult. Experiments with transparent surgical foil were unsuccessful: even with the help of an assistant, application of the adhesive foil in the uneven neck area, for example, was very difficult if a large area had to be covered. I have been using household "cling film" which has been sterilised in ethylene oxide after being packed in crepe paper. The film is easy to apply and adheres well to the skin. A small hole can be easily made and the cover is easy to remove after the procedure. This aid is very helpful especially in catheterising the internal jugular vein in infants. We use a puncture set and the guide wire technique (a-System; Sterimed, Saarbrticken). Under the transparent cover, joints in the anaesthetic tubing remain visible. The film also offers advantages for other kinds of puncture, such as peridural catheterisation. Department II, Anaesthesiology Centre, Medizinische Hochschule Hannover

3000 Hannover 61, West Germany

BERNHARD PANNING