Audrey A. Dawson

p53 mutation in the myelodysplastic syndromes.

We have studied point mutations in exons 5-8 of the p53 gene in the myelodysplastic syndromes (MDS) by using polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) analysis and direct nucleotide sequencing. The subtypes examined were: refractory anaemia (RA), refractory anaemia with ring sideroblasts (RARS), chronic myelomonocytic leukaemia (CMML), refractory anaemia with excess blasts (RAEB), refractory anaemia with excess blasts in transformation (RAEBt), and acute myeloid leukaemia (AML) which had evolved from MDS. 26 cases of MDS were studied. 12 of these were sequentially sampled but none changed its p53 status during the time of the study (18 months). Four mutations (one nonsense and three missense) were identified. Each case with a mutation was of an advanced MDS subtype, suggesting that p53 mutation in these diseases is a terminal genetic event in the process of leukaemogenesis. The nonsense mutation inserted a premature stop codon in a case of AML which had evolved from RAEB; this mutation has been reported before in both chronic myeloid leukaemia (CML) and Burkitts lymphoma. The three missense mutations have not previously been reported in haematological malignancies.

HAEMODIALYSIS FOR A HAEMOPHILIAC WITH HUMAN IMMUNODEFICIENCY VIRUS

Long-term dialysis treatment has been undertaken only infrequently in patients with haemophilia and end-stage renal disease. This is the first report of maintenance haemodialysis in a haemophiliac with serological evidence of human immunodeficiency virus (HIV). In March 19 8 7 a 44-year-old male with severe haemophilia A (factor VIIIc level less than 1%) required dialysis for endstage renal disease. Although renal biopsy was not performed it was presumed that the renal failure was due to chronic glomerulonephritis, on the basis of longstanding renal impairment and smooth shrunken kidneys on ultrasound examination. From October 1985 he had been persistently seropositive for HIV antibodies, and in June 1987 developed HIV antigenaemia. He had not developed any sequelae of HIV infection, which was thought to have been contracted from factor VIII infusions. When end-stage renal disease developed, in March 1987, an arteriovenous shunt was inserted, under factor VIII control, between the right cephalic vein and radial artery. Apart from some bleeding during and after the initial dialysis, there have been no complications with the shunt. The patient now dialyses for 6 h, twice-weekly. He receives 1000 units of factor VIII concentrate immediately after dialysis, and heparin has not been required during dialysis. The patient uses a designated haemodialysis machine, in a ward separate from the main dialysis unit. Dialysis staff wear masks, gloves, gowns and goggles when initiating and terminating dialysis, and shower immediately after dialysis. Although the incidence of end-stage renal disease does not appear significantly increased for patients with haemophilia (Small et al. 1982) the paucity of reports in the literature perhaps suggests that dialysis is rarely undertaken for such patients, possibly because of anticipated problems with vascular access and haemostasis. In practice we, and others (Koene et al, 1977; Sechas et al, 1981), have found that such difficulties are relatively easily overcome. Moreover, successful renal transplantation has been described in a haemophiliac with a factor VIIIc concentration of less than 1% (Koene et al. 1977). Despite the extra costs in terms of accommodation, equipment and staffing, maintenance haeniodialysis treatment was undertaken in preference to continuous ambulatory peritoneal dialysis (CAPD). There were several reasons for this decision. CAPD has the advantage of allowing treatment at home but was considered to be associated with an increased risk of infection in an already immunocompromised patient and the possibility of serious intraor retroperitoneal bleeding. For an individual with severe haemophilia. evidence of HIV infection and many intercurrent problems, there seemed to be an advantage in having a designated hospital base with nursing staff experienced in the infection control procedures outlined in the Rosenheim report (Rosenheim, 19 72). An arteriovenous shunt was chosen as vascular access because it was thought that the insertion of needles into an arteriovenous fistula would cause repeated haematomata formation, and therefore permanent occlusion, as previously described (Sechas et al, 1981). Moreover, the frequent use of needles in an HIV antibody positive patient was considered an added potential risk to staff. Haemodialysis has thus far proved to be a practical and worthwhile treatment for this haemophiliac with asymptomatic HIV infection. The incidence of end-stage renal failure increases markedly for patients with AIDS, and despite haemodialysis such patients have a poor prognosis (Rao et al. 1987). There, is as yet, no data on the development of renal failure for patients with asymptomatic HIV infection. It is unlikely, however, that this patient’s renal disease was related to HIV, as he was known to have longstanding and progressive renal impairment prior to contracting HIV infection.

The Effect of Age on the Diagnostic Value of Greying of the Hair in Addisonian Pernicious Anaemia

The present degree of greying of the head hair, and a history of the age of onset of greying, were noted in 121 patients with Addisonian pernicious anaemia and in 200 non-anaemic controls. Greying occ