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Summary A total of 733 rhesus positive women with antibodies were found during antenatal screening of 380 790 pregnancies in South and Mid Wales over a 30‐year‐period. A steady increase was observed in the frequency of antibodies, particularly non‐rhesus antibodies and the mothers concerned had a significantly increased history of previous blood transfusion. In 50 per cent of those with non‐rhesus antibodies, transfusion was the only stimulus. Conversely, for the majority (61 per cent) of women with rhesus antibodies feto‐maternal incompatibility was the sole apparent stimulus. No identifiable stimulus could be found in 25 per cent of women with anti‐E and 13 per cent of those with anti‐Kell. Compared to rhesus negative mothers with anti‐D severe clinical haemolytic disease of the newborn was uncommon, but in 75 per cent of rhesus positive mothers with infants carrying the homologous antigen, there was some evidence of haemolytic disease. Anti‐c̄ was much the worst in this respect with 19.4 per cent of infants needing transfusion. The probability of having an incompatible infant was much less for the mothers with non‐rhesus antibodies (27.3 per cent) and of these infants only 5.7 per cent needed transfusion.

Amonafide (benzisoquinolinedione, NSC 308847) is a new synthetic imide antineoplastic agent with DNA intercalative properties that has been evaluated in a phase I clinical trial. The drug was administered as a single intravenous (IV) infusion over 30 to 120 minutes repeated every 28 days. Ninety-five courses of therapy at doses ranging from 18 to 1,104 mg/m2 were administered to 38 patients with refractory solid tumors. Granulocytopenia was dose limiting. Leukopenia was seen in 13 of 31 courses at doses of 690 mg/m2 or greater. Life-threatening granulocytopenia (less than or equal to 250 microliters) was noted in 1/6 patients treated at 800 mg/m2, 1/8 patients treated at 918 mg/m2, and 2/5 patients treated at 1,104 mg/m2. No definite relationship between myelotoxicity and prior treatment status was noted. Rate-of-infusion dependent, nonhematologic toxicities included diaphoresis, flushing, dizziness, and tinnitus, all of which were ameliorated by increasing the duration of drug infusion to 120 minutes. In addition, nausea and vomiting (grades 1 and 2) were seen in 29/56 courses at doses greater than or equal to 519 mg/m2, but were easily controlled by phenothiazine antiemetics. Amonafide plasma and urine concentrations were determined by high-pressure liquid chromatography (HPLC). Plasma concentrations declined biexponetially with a terminal harmonic mean terminal half-life (t 1/2) of 5.5 h. The mean apparent volume of distribution at steady-state and total body clearance were 532 L/m2 and 84 L/h/m2, respectively. Less than 5% of the total dose of amonafide was excreted unchanged in the urine. Antitumor activity has been noted in one patient with non-small-cell lung cancer (one complete response exceeding 29 months duration) and in one patient with prostatic cancer (complete pain relief and improvement in bone scan for 9 months). The recommended dose for phase II trials with this schedule of amonafide is 918 mg/m2 with dose escalation to amonafide is 918 mg/m2 with dose escalation to myelotoxicity.

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