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In the period between January 1973 and September 1982, 57 patients with advanced epithelial ovarian cancer were treated with a chemotherapy regime of methotrexate, thiotepa, and vincristine. A 5-year survival rate of 24.1% was obtained. The chemotherapy regime was based on the mode of drug action and information gained from experimental work on fresh explant cultures of human tumor. The regime was well tolerated and the survival rate is similar to results obtained from other regimes recently reported.

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The pattern of haemoglobin production changes at the embryonic, fetal and postnatal stages of human development, reflecting the expression of different globin genes in both the alpha-like and beta-like gene clusters. Recent studies have identified alterations in the state of DNA methylation and sensitivity to nuclease digestion associated with developmental expression of the globin genes in red blood cell precursors, but the mechanism initiating these changes remains unknown. Despite the screening of large numbers of blood samples from newborn infants, no mutants have been found which affect the timing of these changes (with one possible exception involving a chromosomal translocation), thus necessitating alternative approaches to analysing the cellular basis for the timing of haemoglobin switching. Although many mechanisms are possible, the initiation of the switch from fetal to adult haemoglobin could be regulated essentially either by a developmental clock inherent to haematopoietic stem cells or by an inductive environment, and in an attempt to distinguish between these possibilities, we have transplanted sheep fetal haematopoietic tissue into adult animals. Although previous experiments of this type produced conflicting results, the accumulated results presented here demonstrate that the pattern of haemoglobin production after transplantation is determined largely by the gestational age of the fetal donor cells.

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The right kidney of 13 Large White female pigs was irradiated with single doses of 250 kV X-rays in the range 7-12.6 Gy. Sequential measurements of individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were carried out by means of 99mTc-DTPA and 131I-hippuran renography for periods up to 24 weeks after irradiation. GFR levels increased in irradiated and unirradiated contralateral kidneys 2 weeks after treatment compared with age-matched controls. ERPF values exhibited a small increase in a proportion of animals. Renal function then declined in irradiated kidneys in a dose-dependent manner. A dose of 7 Gy resulted in a decline followed by subsequent recovery. After doses of greater than or equal to 8.8 Gy GFR and ERPF declined rapidly, reaching minimal levels by 6-12 weeks, the time depending on the dose. The reduction in ERPF was quantitatively greater than that for GFR. In animals receiving greater than 8.8 Gy the irradiated kidney contributed in the order of only 10% of the total ERPF. The reduction in GFR resulted in a prompt functional compensatory response in GFR in the unirradiated contralateral kidney. In terms of ERPF, a compensatory response was not evident until weeks 20-24. The results indicated that the radiation tolerance dose of the pig kidney following unilateral irradiation with single doses of X-rays was approximately 8 Gy.

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A prerequisite for elucidating the effect of radiation on porcine renal function is the development of non-invasive methods for accurate quantification of unilateral glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The techniques presented here are (a) measurement of unilateral kidney filtration fraction (FF) determined by analysis of the early rise of the kidney's time-activity curves following the injection of tubular ([131I]hippuran) and glomerular ([99mTc]DTPA) tracers, and (b) deconvolution of the respective renogram. Unilateral FF values are obtained by calculating the ratio of glomerular to tubular clearances. Results for 23 female large white pigs indicate a highly significant correlation (r = 0.91, P less than 0.001) between computed FF values and those obtained from the plasma disappearance curves of [99mTc]DTPA and [131I]hippuran. Deconvolution of the renogram allows estimation of the mean transit time (MTT) for [99mTc]DTPA and [131I]hippuran, these are 6.94 +/- 1.87 and 6.86 +/- 1.44 min respectively. In addition, FF values calculated from the H0 values are significantly correlated (r = 0.7, P less than 0.05) with estimates from plasma disappearance curves of the tracers. Therefore these techniques appear to provide accurate non-invasive methods for determining individual porcine kidney function.

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The disposition of [14C]pranolium chloride, a dimethyl quaternary derivative of propranolol, has been studied in rats, mice and hamsters after oral parenteral dosage. 2. Elimination of 14C occurred largely via the kidneys after parenteral dosage, but biliary excretion was significant. Pranolium chloride was excreted unchanged and as a conjugate, and was also metabolized to 1-naphthol which was conjugated. 3. The radiolabel was localized in the liver, kidneys, heart, lungs and gastro-intestinal tract of the rat, but did not pass the placental or blood-brain barriers to any appreciable extent. Unchanged pranolium chloride was localized in rat cardiac tissue for at least 6 h after i.v. dosage. 4. Pranolium chloride was poorly and variably absorbed from the gastro-intestinal tract of animals. Peak plasma levels occurred between 10 min and 1 h. The absorption of the pranolium cation was marginally increased after prolonged fasting, but was not affected by the presence of alternative anions.

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