A Phase I study of combined modality (90)Yttrium-CC49 intraperitoneal radioimmunotherapy for ovarian cancer.

PURPOSE: The purpose of this study was to determine the feasibility and maximum tolerated dose of (90)Yttrium-CC49 ((90)Y-CC49) as the radioimmunotherapy (RIT) component of an i.p. combined modality treatment for recurrent ovarian cancer. EXPERIMENTAL DESIGN: A Phase I trial of (90)Y-CC49 RIT was conducted in ovarian cancer patients who had persistent or recurrent intra-abdominal disease, had failed one or two prior chemotherapy regimens, and demonstrated TAG-72 expression. Patients were treated with a previously established combined modality treatment protocol of s.c. IFN alpha2b, i.p. paclitaxel, and increasing dosages of i.p. (90)Y-CC49. Patients were monitored for toxicity, generation of human antimouse antibody response, and clinical efficacy. RESULTS: Twenty eligible patients were treated per study specifications. All patients had been treated with debulking and paclitaxel/carboplatin-based chemotherapy at initial diagnosis. The patients included 11 patients with persistent disease at the time of second look laparotomy and 9 patients with delayed recurrence. Patients were treated with i.p. (90)Y-CC49 given in combination with s.c. IFN alpha2b (dose of 3 x 10(6) units for a total of four doses) and i.p. paclitaxel (dose of 100 mg/m(2)). RIT treatment was associated with primarily hematological toxicity. The maximum tolerated dose of i.p. (90)Y-CC49 was established at 24.2 mCi/m(2) in this combined regimen. Of nine patients with measurable disease, two had partial responses lasting 2 and 4 months. Of 11 patients with nonmeasurable disease, median time to progression was 6 months in 7 patients who recurred; 4 of these patients remain no evidence of disease at 9+, 18+, 19+, and 23+ months. CONCLUSIONS: (90)Yttrium-CC49-based RIT in combination with IFN alpha2b and i.p. paclitaxel is feasible and well tolerated at a dose of < or =24.2 mCi/m(2).     

Effect of warfarin on factor vii formation by a cell-free system from rat liver

A study was conducted on the effect of warfarin on factor VII formation by a cell-free system from rat liver. Administration of warfarin to the rat from which the liver is obtained results in a marked decrease in factor VII formation by the liver homogenate. The rate of fall of factor VII formation was considerably more rapid than the rate of disappearance of factor VII from warfarin-treated rats.

Restoration of factor VII formation upon the administration of vitamin K to warfarinized rats was also investigated. Factor VII was not made by homogenates prepared from livers removed from the rat immediately after administration of vitamin K, although slices prepared from such livers were able to make the clotting factor. However, homogenates prepared from livers taken a half hour or longer after giving vitamin K were able to make factor VII. These results suggest that vitamin K must be modified before it can participate in clotting factor formation, and that under the condition of these experiments this modification can take place in slices but not in homogenates.     

Accuracy of men's recall of their partner's time to pregnancy

BACKGROUND: Occupational studies of fertility often rely on men's report of time to pregnancy (TTP). We assessed accuracy of men's report of TTP compared with TTP derived from data from their female partners. METHODS: Men from the Dieckmann diethylstilbestrol cohort were interviewed to assess fertility. Men were asked TTP for their most recent pregnancies. Their female partner was subsequently interviewed separately; TTP derived from her data was used as the gold standard. Our analysis was based on 202 couples. RESULTS: Men's report was identical to the women's-derived TTP in 32% of couples; 74% differed by no more than 2 cycles. Men tended to underestimate TTP (mean difference = -1.2 cycles). Weighted kappa was 0.5 overall and varied by the man's education, the number of pregnancies he had fathered, his stated confidence in reporting, his exposure to diethylstilbestrol, pregnancy planning, and whether he was still married to the index partner. CONCLUSIONS: Overall accuracy of men's report of TTP was reasonably good, particularly for men who had fathered only one pregnancy.     

Maternal thyroid hormone increases HES expression in the fetal rat brain: an effect mimicked by exposure to a mixture of polychlorinated biphenyls (PCBs)

Thyroid hormone is known to be essential for normal brain development both before and after birth, but much less is known about the role of thyroid hormone development before birth. In rodents, thyroid hormone of maternal origin can selectively regulate gene expression in the fetal cortex; HES1 was identified as a putative thyroid hormone responsive gene in the fetal cortex. Using in situ hybridization, we now confirm that thyroid hormone administration to pregnant rats can increase the abundance of HES1 mRNA in the fetal cortex on gestational day 16 (G16). In separate experiments, we found that maternal exposure to polychlorinated biphenyls (PCBs) increases HES expression similarly. Western analysis of proteins extracted from fetal cortex did not confirm that Notch-1 or Notch-3 activation was associated with treatment effects on HES expression. However, considering the role of HES proteins in fate specification of cortical neurons, these findings suggest that thyroid hormone, and PCB exposure, may influence fate specification of cortical neurons.     

Multicenter evaluation of two flow cytometric methods for counting low levels of white blood cells

BACKGROUND: Flow cytometric methods can be used to count residual white blood cells (WBCs) in WBC-reduced blood products, which should contain fewer than 1 x 10(6) WBCs per unit (approximately 3.3 WBCs/ microL). In this study two flow cytometric methods for counting WBCs under routine conditions in nine laboratories were evaluated. STUDY DESIGN AND METHODS: Panels of red blood cells (RBCs), platelets (PLTs), and plasma were prepared containing 33.3, 10.0, 3.3, 1.0, and 0.3 WBCs per microL and counted with flow cytometric methods (either LeucoCOUNT, BD Biosciences, four laboratories; or LeukoSure, Beckman Coulter, five laboratories). Requirements were that at the level of 3.3 WBCs per microL, coefficient of variation was < or =20 percent and accuracy was > or =80 percent. Routine flow cytometric quality control (QC) data of WBC-reduced blood products from two laboratories were analyzed. RESULTS: At the level of 3.3 WBCs per microL, none of the laboratories met the requirements for all three blood products. The LeucoCOUNT method met requirements at more laboratories than the LeukoSure method for RBCs and PLTs, but the opposite was true for plasma. Routine QC data showed that >99 percent of the flow cytometric measurements for WBC-reduced products was below the 95 percent prediction interval at 3.3 WBCs per microL. CONCLUSION: None of the laboratories met the requirements for accuracy and precision for all three blood products. Nevertheless, routine results showed that in >99 percent of the products, WBC counts were below guideline limits. Therefore, both flow cytometric methods are suitable for QC with pass-fail criterion.