Blood cyclosporine level soon after kidney transplantation is a major determinant of rejection: insights from the Mycophenolate Steroid-Sparing Trial

Target organs express antigens directly recognized by antigen-specific T cells, thereby precipitating rejection. When early T-cell activation is inhibited, there is a low risk of rejection. We sought to determine the predictive values of serial posttransplant blood cyclosporine trough (C(0)) concentrations to minimize the risk for a first rejection episode compared with 2-hour postdose (C(2)) drug concentrations. The final aim of the study was to identify a concentration range for the best predictive pharmacokinetic parameter that should be targeted to reduce the risk of rejection. This possibility was explored in 334 de novo kidney transplant recipients who participated in the prospective, multicenter Mycophenolate Steroid-Sparing Trial. Among measurements performed during the first 6 months postsurgery, cyclosporine C(0) levels measured early after transplantation were the strongest predictor of acute graft rejection. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while patients with levels lower than 300 ng/mL showed a more than double risk. Cyclosporine trough values predicted allograft rejection with an accuracy of 74%, while C(2) levels had no predictive value. These findings underline the need to target cyclosporine therapy early posttransplant to modulate T-cell activation.     

Effect of thyroid hormones and IGL in vivo on protein synthesis in the mitochondria of thyroidectomized animals

The effect of tri-iodothyronine (T₃) and IGL on the intensity of incorporation of L-[¹⁴C]tyrosine and on the rate of protein synthesis in the liver mitochondria of thyroidectomized rats and on the radioactivity of the amino-acid pool in the liver was investigated. The intensity of incorporation of L-[¹⁴C]tyrosine into proteins in the liver mitochondria of thyroidectomized animals and the rate of protein synthesis in them were found to be only half of their values in animals undergoing mock operations. Administration of T₃ or IGL to thyroidectomized rats restored protein synthesis in the liver mitochondria to normal. IGL had a similar effect to T₃ on all biochemical indices studied. The absence of thyroid hormones circulating in thyroidectomized animals or administration of T₃ or IGL to them did not change the radioactivity of the free tyrosine pool in the liver tissue.Central Biophysical Laboratory, Bulgarian Academy of Sciences, Sofia. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 8, pp. 167–170, August, 1978.     

Family planning in big town conditions depending on the birthplace of the parents.

The purpose of this article is to determind what effect if any place of birth has upon family size, both actual and ideal, in the Bulgarian city of Plovdiv. It is a retrospective study of 181 families comprised of 2 cohorts, one with couples married for 5 years, the other with couples married for 10 years. The author found that place of origin, whether rural, other towns, Plovdiv itself, or a combination of any two of those, had no significant effect on desired or ideal family size. 79.1% of the women considered the two-child family ideal. When asked to specify an ideal family size in the light of their personal experience, however, 17.8% preferred a single-child family. 18.6% in the 10-year cohort preferred this size and 16.8% in the 5-year cohort. This evidence that individuals retrospectively modify their ideal family size downwards. Those couples in which both partners came from villages had the highest actual family size (1.62). For the total contingent the average number of children was 0.14, smaller than the planned one.     

Sucessful pregnancy outcome following three severe placental abruptions and intrauterine fetal death in the patient--heterozygous carrier of R506Q mutation of factor V (Leiden)

A case of successful pregnancy outcome is reported in a patient with 3 preceding severe placental abruptions with intrauterine fetal death and caesarean deliveries. In the course of the current pregnancy heterozygosity for R506Q mutation of factor V (Leiden) was diagnosed in 26 weeks of gestation [w.g.] and low molecular weight heparin [LMWH] therapy initiated. Maternal condition was stable until delivery and all laboratory findings were within normal range. The fetus was followed up by ultrasound biometry and Doppler blood flow studies. From 28 w.g. on NST and biophysical profile were included. An emergency caesarean section was performed in 34 w.g. because of contractions not responding to tocolysis. The newborn was in good condition with weight and length corresponding to the 10th centile for gestational age [g.a]. Histologic study of the placenta showed anemic infarctions and recent haemorrhages in the basal and the chorionic plate. The initiation of LMWH therapy in the case reported was late (26 w.g.). By that moment there was already evidence of impaired fetal growth with fetal biometry corresponding to the 10th centile for g.a. After LMWH therapy was started no further slow down of fetal growth was registered. Successful pregnancy outcome may be related not only to LMWH therapy but also to other factors like active fetal monitoring after 28 w.g. and the emergency caesarian delivery immediately after the onset of uterine contractions. Patients with past obstetric history of severe preeclampsia, placental abruption or fetal growth restriction have to be screened for hereditary or acquired thrombophilia. If a thrombophillic state is present early LMWH therapy has to be considered. It is aimed to prevent anaemic placental infarctions and thrombotic complications.     

Respiratory and hemodynamic monitoring during laparoscopy and two computer-controlled TCI anesthesiologic technique

Forty women under general anaesthesia (computer-controlled TCI-infusion) in two groups were subjected to non-invasive haemodynamic monitoring together with arterial gasometry and capnography. Simultaneous continuous monitoring of aortic blood flow and PetCO2 allows an undelayed recognition of major circulatory disturbances, before significant changes in heart rate and arterial pressure occur.