Improved reaction conditions for the synthesis of new NKP-1339 derivatives and preliminary investigations on their anticancer potential.

The very promising results of Na-trans-[RuCl4(1H-indazole)2] (NKP-1339) in clinical studies have fuelled renewed interest in the research and development of ruthenium(III) coordination compounds for cancer therapy. By applying an improved synthetic approach to this class of coordination compounds, six new examples of the general formula (cation)-trans-[RuCl4(azole)2], where (cation) = tetrabutylammonium (Bu4N)(+) (1, 2), sodium (3, 4), azolium (5, 6), and azole = 1-methyl-indazole (1, 3, 5), 1-ethyl-indazole (2, 4, 6), have been prepared. All compounds have been characterized by elemental analysis, electrospray ionization (ESI) mass spectrometry, UV-vis-, and NMR-spectroscopy and, if possible, X-ray diffraction analysis. Furthermore, the influence of the alkyl substituent at the position N1 of the indazole backbone on the stability in aqueous media as well as on the biological activity in three human cancer cell lines (CH1, A549, and SW480) and on the cellular accumulation in SW480 cells is discussed.

Chromosome alterations in renal cell carcinoma of childhood may correspond to aberrations in adults.

A 5.5-year-old girl with renal cell carcinoma and chromosomal abnormalities is described. Morphology was diagnostic of an adenopapillary renal cell carcinoma. The karyotype was 57, XX, +X, +2, +3, +4, +7, +12, +13, +16, +17, +20, +21[8]/58,idem, +17[17]. This karyotype has not previously been described in the rare cases of childhood renal cell carcinoma. It is similar to the karyotypes described in adults of the same morphologic subtype. This poses the question whether different types, from a genotype point of view, of renal cell carcinoma exist in childhood.

[Infantile constipation and Allomin-lactulose. Treatment of infantile obstipation in infants fed with breast milk substitutes. A controlled clinical trial of 2 per cent and 4 per cent Allomin-lactulose]. / Spaedbarnsobstipation og Allomin-laktulose. Behandling af obstipation hos spaedbørn ernaeret med modermaelkserstatning. En kontrolleret klinisk undersøgelse af 2% og 4% Allomin-laktulose.

The Authors investigated the effects of Allomin with admixture of 2% and 4% lactulose on constipation in infants aged 0-6 months reared on breast-milk substitutes. The investigation was randomized and double-blind and was carried out during the period 1.4.1987-31.7.1988 on non-hospitalized infants in the counties of Funen and North Jutland in cooperation with the health visitors in these regions. Constipation was defined as hard and difficult defaecation and the trial period lasted for 14 days. Parents of the infants who participated classified the infants' motions according to consistence and degree of difficulty in defaecation on special forms. A total of 220 children participated and these received, after randomizing, either Allomin-lactulose 2% or 4% as the only breast-milk substitute during the period of observation. The effect of treatment was defined as "no constipation" i.e. all motions during 24 hours described as easy and of normal or thin consistence. In addition, the effect was measured by the parents' general impression of what the infant thrived best on. With both of the preparations, treatment was effective in over 90% of the infants in both the groups without significant difference. The effect occurred gradually and, in some cases, up to 8-10 days after initiation of treatment without significant difference in the rate of effect between the groups. After the effect had commenced, significantly fewer thin motions occurred in the 2% group than in the 4% group. 92% of the infants in the 2% group and 91% in the 4% group wanted to continue the Allomin-lactulose preparation rather than the usual breast-milk substitute. A retrospective questionnaire to parents of 97 infants who had continued with Allomin-lactulose 2% was answered by 84.(ABSTRACT TRUNCATED AT 250 WORDS)

[Rhesus immunization in a rhesus-positive pregnant woman: fetal erythroblastosis caused by the rhesus antibody anti-C]. / Rhesusimmunisering hos rhesus-positiv gravid: erythroblastosis foetalis forårsaget af rhesusantistoffet anti-C.

A rhesus-D-positive woman aged 32 years with two previous pregnancies was delivered of an infant with erythroblastosis foetalis caused by the rhesus antibody anti-c produced by alloimmunization during pregnancy. Screening for antibodies in the 12th week of pregnancy yielded negative results. No screening was undertaken in the 35th week of pregnancy. The infant was born with severe anaemia. Following delivery, the anti-c alloimmunization was diagnosed and three exchange transfusions were administered. On the fourth day of life, the infant developed the inspissated bile syndrome. No cerebral disorders were demonstrated. Antibody screening of rhesus-positive women has now been introduced at the 35th week of pregnancy to avoid similar cases.

Maintenance chemotherapy for childhood acute lymphoblastic leukemia: relation of bone-marrow and hepatotoxicity to the concentration of methotrexate in erythrocytes.

To explore the clinical significance of the concentration of methotrexate (MTX) in erythrocytes (E-MTX), 42 boys and 31 girls were studied during maintenance chemotherapy for childhood acute lymphoblastic leukemia for periods of 3-22 months (median, 8 months) at an unchanged dose of MTX. For each study period, a weighted mean of white cell counts (mWBC), absolute neutrophil counts (mANC), and serum aminotransferases (mAT) were calculated, using as weights the intervals from sampling until the next WBC, ANC, or AT determinations were done. In 17 patients who underwent at least six measurements of E-MTX during a period in which the MTX dose remained unchanged for up to 22-months, the median intraindividual coefficient of variation for E-MTX was 10% (range, 5%-22%). For each patient, a mean of all E-MTX values (mE-MTX) during a study period (range, 1-15 measurements; median, 3) was used as an index of the RBC accumulation of MTX at the prescribed dose of MTX. Among 42 patients receiving full-dose MTX (greater than 17.5 mg/m2), the mE-MTX ranged between 3.4 and 9.6 nmol hemoglobin (Hb) (interindividual coefficient of variation, 33%). The mE-MTX was significantly related to the MTX dose (r = 0.45, P = 0.00003). The mWBC and mANC were both significantly related to the mE-MTX (mWBC: r = -0.31, P = 0.004; mANC: r = -0.35, P = 0.02), but not to the dose of MTX (mWBC: r = -0.08, P = 0.25; mANC: r = -0.22, P = 0.08). Each of four patients with a persistent rise in AT above the upper normal limit (40 IU/l) and an mAT of greater than 80 IU/l had an mE-MTX of greater than 6.5 nmol/mmol Hb. Due to its low intraindividual variation, E-MTX may be useful for detecting persistent or intermittent failure of patient compliance. Its prognostic significance and its clinical value in MTX dose adjustment should be explored in prospective studies.

Desamino-D-arginine vasopressin in childhood nocturnal enuresis.

The effect of desamino-D-arginine vasopressin was investigated in a double-blind study of 37 children more than 9 years old with nocturnal enuresis resistant to conventional therapy. A significant reduction of wet nights was observed but as soon as the medication was stopped the children reverted to earlier bedwetting habits.

Hypertensive peaks in the pathogenesis of intraventricular hemorrhage in the newborn. Abolition by phenobarbitone sedation.

Mean arterial blood pressure (MABP) was measured continuously for 3 to 5 days after birth in 27 premature infants with a birth weight under 1500 g, and who required umbilical artery catheterisation. All had respiratory distress syndrome (RDS). Intraventricular hemorrhage (IVH) occurred in 9 infants (33%), diagnosed by computered tomography (CT). IVH was more common in infants of lower gestational age, in infants delivered vaginally and in infants with perinatal asphyxia. Variable increases in MABP over the resting value occurred in all infants associated with increases in both active and passive motor activity. In 6 infant pairs matched for birth weight, gestational age, mode of delivery and severity of perinatal asphyxia, the infants who developed IVH had higher peak MABP valued compared to matched controls. Resting and minimum MABP values were not different in the two groups. We conclude that the large increases in arterial blood pressure which occur with both spontaneous motor activity and in association with nursing procedures, are an important cause of development of IVH in very low birth weight infants. An example is given to show that pressure peaks can be abolished by phenobarbitone sedation.

Hyperlipemia among 1407 Danish children whose fathers have died from ischemic heart disease before age 45.

1407 children whose fathers had died from ischemic heart disease before age 45 were investigated. 15% had hypercholesterolemia and 8% hypertriglyceridemia at visit 1. At visit 2 and 3 this number of children with hyperlipemia fell to a minimum of 3% and 1.4%, resp. which is around 10 times higher than in a reference population. 1.8% of the children had familial hypercholesterolemia (FH) which is 10-15 times higher than in a reference population. These findings indicate that serum lipids should always be measured in children from such coronary heart risk families, and a decision made whether or not their permanent hyperlipemia should be treated.