Gender is an essential determinant of blood transfusion in patients undergoing coronary artery bypass graft procedure

STUDY OBJECTIVE: To determine factors that account for gender difference in the need for blood transfusion in coronary artery bypass graft (CABG) patients. DESIGN: Retrospective study of consecutive patients. SETTING: Anesthesiology department of a teaching hospital. PATIENTS: 253 CABG patients (163 males and 90 females). INTERVENTIONS: Packed red blood cells (PRBCs), platelets, and fresh frozen plasma (FFP) were transfused depending on the need of each patient. MEASUREMENTS AND MAIN RESULTS: For each patient, we recorded the gender, age, weight, height, body surface area (BSA), and duration of surgery. Hematocrit (Hct) levels prior to surgery, end of surgery, and at discharge from the hospital were recorded. PRBC administration and use of FFP and platelets were noted. Differences between the data for female and male patients were evaluated using Student's t-test, Chi-square test, and regression analysis. Approximately 60% female and only 20% male patients received PRBCs intraoperatively, whereas 78% females and only 43% males received PRBCs during their entire hospital stay. On average, females received 1.20 units of PRBCs intraoperatively and 2.38 units during the entire hospital stay, while the males received 0.31 units and 1.36 units for similar periods. Gender differences in PRBC transfusion persisted even when females and males were compared within the same subgroups for age, weight, duration of surgery, and preoperative Hct. PRBC units given intraoperatively had a significant correlation with age and preoperative Hct in females, but they had a significant correlation with age, preoperative Hct, and duration of surgery in males. PRBCs given during the entire hospital stay, however, had significant correlation with age, preoperative Hct, and duration of surgery in both females and males. Multiple logistic regression analysis showed that the probability of a patient receiving or not receiving PRBC transfusion is significantly influenced by age, preoperative PRBC mass, duration of surgery, and gender. CONCLUSION: Gender is an independent essential determinant of blood transfusion in CABG patients, and it may interact with age, weight, preoperative Hct, duration of surgery, and other factors in determining the probability of transfusion.     

Estrogen modulates the recruitment of myelopoietic cell progenitors in rat through a stromal cell-independent mechanism involving apoptosis

Loss of ovarian function leads to a significant increase in the number of bone-resorbing osteoclasts. Estrogen replacement is known to manifest bone protective effects in the treatment of postmenopausal osteoporosis. In the present study, we used ovariectomized rats to examine the effects of estrogen loss at the osteoclast progenitor colony forming unit-granulocyte macrophage (CFU-GM) level. A significant increase in CFU-GM number was observed as early as 7 days following ovariectomy, and correlated directly with an increase in the number of osteoclast-like cells generated in marrow cultures. The increase in CFU-GM following ovariectomy was abrogated in animals that received estrogen treatment in vivo. A similar suppressive effect was observed on CFU-GM number when ovariectomized rat marrow was treated with estrogen in vitro. This effect was blocked in the presence of the estrogen antihormone ICI 164,384. Thus, the data suggest the possibility that estrogen exerts a direct effect on osteoclast progenitors, and does so through the estrogen receptor-mediated mechanism. Ovariectomy also led to an increase in the early hematopoietic stem/progenitor cell population (Thy 1.1+ cells) as determined by FLOW cytometry methods. Morphological changes as well as terminal deoxynucleotidyl transferase assays revealed that estrogen treatment negated growth factor-induced proliferation of these early progenitors by promoting apoptosis. The cellular effects of estrogen in vitro together with the immunocytochemical detection of the estrogen receptor in these cells, strongly support the contention that in addition to osteoclast progenitors such as CFU-GM, earlier hematopoietic progenitors are also unique cellular targets for estrogen action.     

Comparative chondrogenesis of human cell sources in 3D scaffolds

Cartilage tissue can be engineered by starting from a diversity of cell sources, including stem‐cell based and primary cell‐based platforms. Selecting an appropriate cell source for the process of cartilage tissue engineering or repair is critical and challenging, due to the variety of cell options available. In this study, cellular responses of isolated human chondrocytes, human embryonic stem cells and mesenchymal stem cells (MSCs) derived from three sources, human embryonic stem cells, bone marrow and adipose tissue, were assessed for chondrogenic potential in 3D culture. All cell sources were characterized by FACS analysis to compare expression of some surface markers. The cells were differentiated in two different biomaterial matrices, silk and chitosan scaffolds, in the presence and absence of bone morphogenetic protein 6 (BMP6), along with the standard chondrogenic differentiating factors. Embryonic stem cells‐derived MSCs showed unique characteristics, with preserved chondrogenic phenotype in both scaffolds with regard to chondrogenesis, as determined by real time RT‐PCR, histological and microscopical analyses. After 4 weeks of cultivation, embryonic stem cells‐derived MSCs were promising for chondrogenesis, particularly in the silk scaffolds with BMP6. The results suggest that cell source differences are important to consider with regard to chondrogenic outcomes, and among the variables addressed here the human embryonic stem cells‐derived MSCs were the preferred cell source. Copyright © 2009 John Wiley & Sons, Ltd.     

Suppression of murine mammary carcinoma metastasis by the murine ortholog of breast cancer metastasis suppressor 1 (Brms1)

The murine ortholog (Brms1) of human breast cancer metastasis suppressor 1 shares 95% identity to the human metastasis suppressor, BRMS1, in amino acid structure. We tested Brms1 for suppression of metastasis of mouse mammary carcinoma cell line 4T1 in syngenic BALB/c mice, using orthotopic (mammary fat pad) injection as well as intravenous injection. As observed for BRMS1, transfection with Brms1 did not inhibit 4T1 primary tumor formation, but significantly suppressed lung colonization. We also show that Brms1 protein interacts with histone deacetylases, indicating involvement of Brms1 in murine Sin3-HDAC complex, like its human counterpart. Thus, because of similarities with its human ortholog, the results suggest that Brms1 will be useful as a model for studying mechanism of action of BRMS1.     

Recent advances in anti-angiogenic therapy of cancer

Since angiogenesis is critical for tumor growth and metastasis, anti-angiogenic treatment is a highly promising therapeutic approach. Thus, for over last couple of decades, there has been a robust activity aimed towards the discovery of angiogenesis inhibitors. More than forty anti-angiogenic drugs are being tested in clinical trials all over the world. This review discusses agents that have approved by the FDA and are currently in use for treating patients either as single-agents or in combination with other chemotherapeutic agents.     

Identification and characterization of the murine ortholog (brms1) of breast-cancer metastasis suppressor 1 (BRMS1).

We have cloned a novel metastasis-suppressor gene (BRMS1) by differential display, comparing metastatic human breast carcinoma cell line MDA-MB-435 to its metastasis-suppressed human chromosome 11 microcell hybrid. Screening of a murine cDNA library led to the identification of a 1.4 kb cDNA with a sequence revealing 85% homology to human BRMS1 within the open reading frame. The predicted protein sequence for the murine ortholog is 95% identical, suggesting that it is strongly conserved across these 2 species. The cloned cDNA was used to screen a murine strain SV129 BAC library to obtain brms1 genomic DNA. Three BAC clones [226(I4), 226(H4) and 239(N7)] were confirmed to encode the entire brms1 gene. Detailed analysis of BAC clone 226(I4) shows that the gene spans 8.5 kb and, like the human gene, is organized into 10 exons and 9 introns. While the exons share a high degree of homology, there are greater differences when comparing intron structures between the human and murine genes. The 5' upstream region shares about 64% homology with its human counterpart, retaining several of the many putative regulatory elements. Like the human genomic BRMS1, the murine ortholog of the iGnT gene is found upstream of brms1 and the murine ortholog of the RIN1 gene is found downstream of brms1. brms1 was then tested for suppression of metastasis of mouse mammary carcinoma cell line 66cl4 in syngeneic BALB/c mice. Transfection with brms1 did not inhibit 66cl4 primary tumor formation but significantly suppressed its metastatic capability. This suggests that the murine ortholog functions similarly to BRMS1.