Variation in Doppler indices along the length of the cord from the intraabdominal to the placental insertion

AIM. The aim of this study was to assess the feasibility of obtaining umbilical artery Doppler waveforms from the intraabdominal portion (perivesical) of the umbilical arteries and to compare the indices from this site to those from the free loop (FL) of cord placental insertion (PL) and abdominal insertion (AI). METHODS. A cross-sectional study of 71 singleton fetuses of 24-38 weeks of gestation. Umbilical artery Doppler waveforms were obtained from four sites by a single operator and their resulting indices--i.e. resistance index, pulsatility index, and systolic/diastolic ratio--were compared. Waveforms were also obtained from the two perivesical (PVC) arteries and the mean was used for analysis. Statistical analyses were performed using appropriate non-parametric tests. RESULTS: Doppler waveforms acceptable for inclusion in the study were obtained in 100% of cases from the FL site. There were failures to obtain waveforms that met the inclusion criteria in three (4%) cases at the PL site, three (4.2%) cases at the PVC site, and 12 (16.9%) cases at the AI. The three indices fell progressively with gestation from the PVC to the PL sites. There were no significant differences between the two PVC arteries using non-parametric test of mean difference for related samples using Wilcoxon signed-rank test (P > 0.05) for all the indices. The relation between the differences at the two ends of the cord was fairly consistent across gestation. CONCLUSIONS: Doppler velocimetry at PVC site of the umbilical artery is feasible and easy to perform. The indices obtained at this site are higher than those at the other three sites. There is a need for standardization of the site of sampling in order to ensure consistency for clinical application.     

Validation of CanAssist Breast immunohistochemistry biomarkers on an automated platform and its applicability in tissue microarray

CanAssist Breast (CAB) is a prognostic test for early-stage hormone receptor-positive invasive breast cancer. The test involves performing immunohistochemical (IHC) analysis for five biomarkers, namely CD44, ABCC4, ABCC11, N-cadherin, and pan-cadherin. In addition to IHC grading information, three clinical features, i.e., tumor size, grade, and lymph node status, serve as input into the machine learning-based algorithm to generate the CAB risk score. CAB was developed and initially validated using manual IHC. This study’s objectives included: i) automate CAB IHC on an autostainer and establish its performance equivalence with manual IHC ii) validate CAB test using samples in Tissue MicroArray (TMA) format. IHC for CAB biomarkers was standardized on Ventana BenchMark XT autostainer. Two IHC methods were compared for IHC gradings and corresponding CAB risk scores/risk categories. A concordance analysis was done using MedCalc^TM software. The manual and automated IHC staining methods exhibited a high level of concordance on IHC gradings for 40 cases with an Intra-class Correlation Coefficient (ICC) of >0.85 for 4 of 5 biomarkers. 100% concordance was achieved in risk categorization (low- or high-risk), with very good agreement between the risk scores demonstrated by a kappa statistic of 0.83. TMA versus whole tissue section concordance was analyzed using 45 samples on an autostainer, and the data showed 92% concordance in terms of risk category. The results confirm the equivalence between manual and automated staining methods and demonstrate the utility of TMA as an acceptable format for CanAssist Breast testing.     

Scaleup of Immediate Release Oral Solid Dosage Forms

Pharmaceutical Research -     

FISH analysis of an AML-M5a with segmental rearrangements involving 11q23-MLL region

A 66-year-old man was diagnosed 10 years ago with thrombocytosis and treated with hydroxyurea. Recently, his condition deteriorated and he was found to have 68% blasts in the blood and AML-M5a. Conventional cytogenetic analysis and fluorescence in situ hybridization studies using 11-painting and MLL probes showed that chromosome 11 had duplications or triplications; the markers were also derived from the chromosome 11-MLL region. Therefore, we have demonstrated segmental rearrangement of chromosome 11 involving the MLL region resulting in multiple copies of the MLL gene.     

Postrenal Transplant Non-EBV Multiple Myeloma of Donor Origin

Multiple myeloma occurring after solid organ transplantation is a rare condition, with only a few case reports found in the literature. We report a case of Epstein-Barr virus-negative, posttransplant multiple myeloma in a 67-year-old female, presenting 18 months after renal transplantation. Interestingly, fluorescence in situ hybridization analysis of the tumor revealed a Y chromosome in the majority of the cells, indicating that the neoplasm was derived from the donor kidney. To our knowledge, this represents the first reported case with these features.