Double-blind, randomized comparison of the effect of carbetocin and oxytocin on intraoperative blood loss and uterine tone of patients undergoing cesarean section.

OBJECTIVES: A double-blind randomized study involving pregnant women undergoing cesarean section was conducted to compare the effectiveness of a single 100 micrograms intravenous injection of the long-acting oxytocin analog, carbetocin, with that of a standard infusion of oxytocin with respect to intraoperative blood loss. The two treatments also were compared for safety and ability to maintain adequate uterine tone. STUDY DESIGN: The study drug was administered to 57 women during elective cesarean section after placental delivery; blood was collected until abdominal closure. Intraoperative blood loss was calculated with a sensitive colorimetric method. Position, tone of the fundus, and vital signs were assessed up to 24 hours after the operation. The need for additional uterotonic agents was recorded. RESULTS: A single 100 micrograms intravenous injection of carbetocin was as effective as a continuous 16 hour infusion of oxytocin in controlling intraoperative blood loss after placental delivery. Mean blood loss after carbetocin administration was 29 ml less than after oxytocin administration (p = 0.3). Subset analysis deleting two patients who received oxytocic intervention in the operating room and one extreme outlier revealed a mean blood loss of 41 ml less in the carbetocin group (p = 0.14) with lower variances (p = 0.02). The percentage of patients with blood loss of 200 ml or less was greater with carbetocin (79% vs 53%; p = 0.041). Carbetocin enhanced early postpartum uterine involution. The fundus was below the umbilicus in more patients who received carbetocin at 0, 2, 3, and 24 hours on the ward (p < 0.05). There were no significant differences in uterine tone or type or amount of lochia. Additional oxytocin was used to treat three patients for postpartum hemorrhage or persistent uterine atony. All interventions were in the oxytocin group. Vital signs and hematologic values were comparable in each group, confirming similar safety profiles. CONCLUSIONS: A single 100 micrograms intravenous injection of carbetocin is as effective and more reliable than a standard continuous infusion of oxytocin in maintaining adequate uterine tone and preventing excessive intraoperative blood loss during cesarean section after delivery of the placenta. Patients receiving carbetocin required less intervention. Carbetocin was well tolerated.

Epitope mapping of human monoclonal antibodies to HLA-B27 by using natural and mutated antigenic variants.

The epitopes defined by three human monoclonal antibodies (mAbs) (Tr3B6, TrCG10, TrBH12) against HLA-B27 have been mapped by flow cytometry. For this purpose we used murine transfected cells expressing at their surface hybrid antigens between HLA-B7 and -B27 and, in addition, Epstein-Barr virus cell lines expressing the six HLA-B27 alleles B*2701 to B*2706. The results indicated that the mAbs are domain specific. TrBH12 recognizes the first external (alpha-1) domain. Residues critical for the TrBH12 epitope are located in the alpha-1 helix and include the polypeptide stretch 63-76 plus a critical amino acid at position 77. Tr3B6 binds the second external (alpha-2) domain, and one mutation (VAL152----GLU152) destroyed its epitope. TrCG10 also binds the alpha-2 domain.

The hepatic chalone. II. Chemical and biological properties of the rabbit liver chalone.

A factor has been purified from rabbit liver which decreases the incorporation of 3H-thymidine in DNA of regenerating rat liver slices. This effect is due mostly to an inhibition of DNA synthesis from the deoxynucleoside triphosphates. The purified rabbit liver factor thus interferes with the liver cell division cycle. This inhibitor of DNA synthesis is specific for liver cells; it is not toxic for cultured hepatocytes and its action on DNA synthesis is reversible: at low dose, the inhibition of DNA synthesis in regenerating liver slices is transitory. The purified rabbit liver inhibitor is thus a chalone. The purified rabbit liver chalone ultrafiltrates through 1.2 nm pores, is destroyed by trypsine and pronase, carries a negative charge at pH 8.8 and a positive charge at pH 4.6; it is thermostable and likely a small peptide. It also inhibits RNA and protein synthesis in regenerating liver slices. The inhibition of protein synthesis is immediately maximal then decreases with time, while the maximum inhibition of DNA and RNA synthesis appears after a delay. When a low dose of chalone is used (0.2 unit per 5 ml), the inhibition of DNA and RNA synthesis disappears after some time: this is not due to a destruction of the chalone, but to a loss of sensitivity of the slices incubated in Hanks solution. The inhibitor content of liver cells, normal or malignant, seems inversely correlated with their state of growth. It is much lower in the liver of a young animal or in regenerating liver than in adult liver. Hepatomas produced by feeding DAB contain three times less inhibitor than the normal liver. The purified liver chalone is 5-10 times less active on the incorporation of 3H-thymidine in DNA of DAB hepatoma slices than in DNA of regenerating liver slices. It has no apparent action on adult liver slices; this might be due to the fact that 3H-thymidine incorporation into DNA of the adult organ depends, for the greater part, on other processes than DNA replication in hepatocytes.

Inhibition of cell proliferation in the livers of hepatectomized rats by a rabbit hepatic chalone.

A purified chalone isolated from rabbit liver was tested in vitro on regenerating rat liver slices incubated with tritiated thymidine to determine more precisely the phase of the normal cell cycle that was blocked by that substance. Biochemical and radioautographic studies showed that the inhibition of tritiated thymidine incorporation during chromosomal DNA replication resulted chiefly from a block in the G(1)-S transition in the normal cell cycle. Under these conditions the chalone had little inhibitory effect on hepatocytes that were in the S phase of the cell cycle. The inhibitory effects of the liver chalone appeared to be specific for hepatocytes and no significant inhibition of cell division was observed when that compound was tested against intestinal villi or tongue epithelial cells of the rat. When, on the other hand, the purified chalone was injected into rats following partial hepatectomy, not only was an inhibition observed during the G(1)-S transition but an increase in the ratio of metaphases to anaphases was found, suggesting that a block also occurs at metaphase as a result of the action of the purified liver chalone used in this study. The injection of a crude supernatant fluid obtained from rabbit liver homogenates into partially hepatectomized rats resulted not only in a more pronounced block at the G(1)-S transition than was observed when the purified chalone was used, but the supernatant liquid also affected significantly DNA synthesis during the S phase of the cell cycle. These inhibitory effects were observed not only in hepatocytes but in intestinal epithelium and tongue epithelial cells of the rat as well. The rabbit liver supernatant fluid thus appears to contain, in addition to the liver chalone, one or more nonspecific inhibitors of DNA synthesis.