Shaila J. Merchant

MMP-2 Levels are Elevated in the Plasma of Women Who Subsequently Develop Preeclampsia

Objective. To determine levels of matrix metalloproteinase (MMP)-2 and MMP-9, and the tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 in the plasma of women destined to develop preeclampsia prior to the onset of clinical disease. Study Design. Plasma samples were taken from women whose pregnancies were subsequently complicated by preeclampsia and from normal pregnant women at 22 and 26 weeks and at delivery or diagnosis. Following equal protein loading, MMP-2 and 9 and TIMP–1 and 2 were quantified using zymography and Western blot analysis, respectively. Results. Plasma MMP-2 levels were significantly elevated at 22 weeks (p = 0.02) and at diagnosis (p = 0.003) in the preeclampsia group, but there was no difference at 26 weeks. TIMP-1 levels were significantly reduced in the preeclampsia group at 26 weeks (p = 0.0002), but TIMP-2 levels were not quantifiable. Conclusion. At all three gestational time points an imbalance in the MMP-2:TIMP-1 ratio was found in patients who subsequently developed preeclampsia. We speculate that increased net MMP-2 activity may contribute to the endothelial dysfunction that is central to the pathophysiology of preeclampsia.

Exploring the psychological effects of deceased organ donation on the families of the organ donors

Abstract:  Background:  Our specific aim was to investigate whether the donation process hindered or ameliorated the bereavement process for organ donor families, specifically with regard to depression, post‐traumatic stress and grief.

The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre-eclampsia.

Objectives  (1) To investigate the effects of plasma from non‐pregnant, normal pregnant and pre‐eclamptic women on myogenic tone and endothelium‐dependent relaxation; (2) To investigate the role of matrix metalloproteinases (MMPs) in these parameters of vascular function.

The Effects of Preeclampsia and Oxygen Environment on Endothelial Release of Matrix Metalloproteinase‐2

Background: There is evidence of altered vascular endothelial function in women with preeclampsia as well as in the endothelial cells from umbilical vessels of preeclamptic pregnancies. Matrix metalloproteinase (MMP)‐2 is elevated in the plasma of preeclamptic women and is a mediator of vascular reactivity; however, whether MMP‐2 release is altered in preeclamptic endothelial cells is unknown. We hypothesize that MMP‐2 release is enhanced in endothelial cells from preeclamptic compared with uncomplicated pregnancies and that this phenomenon may be mediated by an oxygen‐dependent mechanism. Our specific hypothesis is that cells from normal pregnancies will demonstrate enhanced MMP‐2 release at low oxygen (< 0.5%, 2%) compared to high oxygen (20%), thus mimicking the behavior of preeclamptic cells. Methods: Human umbilical vein endothelial cells (HUVECs) from preeclamptic pregnancies (n = 4) and normal pregnancies (n = 4) were incubated for 12 hr in standard culture conditions (20% oxygen). In a separate series of experiments, HUVECs from normal pregnancies (n = 6) were incubated for 12 hr at < 0.5%, 2%, and 20% oxygen. Supernatants were analyzed for MMP‐2 and tissue inhibitors of metalloproteinases (TIMP)‐1 and ‐2. Results: The HUVECs from women with preeclampsia demonstrated significantly enhanced release of MMP‐2 (p < 0.05), TIMP‐1 (p < 0.001), and TIMP‐2 (p = 0.01) compared to normal cells. MMP‐2 release from HUVECs from uncomplicated pregnancies was significantly elevated at 2% oxygen compared to < 0.5% and 20% oxygen (p < 0.05). TIMP‐1 and ‐2 secretion was not altered with varying oxygen. Conclusions: Preeclamptic endothelial cells demonstrate significantly enhanced MMP‐2, TIMP‐1 and TIMP‐2 release compared to normal cells. Our data show that there are significant effects of oxygen tension on MMP‐2 release from normal cells; however, the magnitude of the enhanced release is small when compared to the differences in MMP‐2 release in cells from preeclamptic and normal pregnancies. Furthermore, TIMP‐1 and ‐2 release is not affected by changes in oxygen. It is unlikely that oxygen is a key mediator of the enhanced MMP‐2, TIMP‐1 and TIMP‐2 release observed in preeclamptic cells.

Matrix Metalloproteinase Release From Placental Explants of Pregnancies Complicated by Intrauterine Growth Restriction

Objective: There is evidence of impaired placental development in intrauterine growth restriction (IUGR). Matrix metalloproteinases (MMPs) are extracellular matrix-degrading enzymes that are released by placental cells during tissue remodelling processes. We hypothesized 1) that release of MMP-2 and -9 is decreased and/or release of tissue inhibitors of metalloproteinases (TIMPs) is increased from placental explants in pregnancies complicated by IUGR and 2) that oxygen levels affect such release. Methods: Placental villous explants from normal (n = 7) and IUGR (n = 7) pregnancies were cultured at high (20%) and low (3%) oxygen levels for 24 hours. Supernatants were analyzed for MMP-2 and MMP-9 by zymography and for TIMP-1 and -2 by western blot analysis. Results: At 20% oxygen there was significantly reduced MMP-2 (P < .05) and TIMP-1 (P < .01) release and a trend for decreased MMP-9 release (P = .07) in explants from IUGR pregnancies compared with normal pregnancies; however, there were no differences at 3% oxygen. TIMP-2 was below detectable levels in all samples. Although MMP-2 and TIMP-1 release was significantly reduced at 3% compared with 20% oxygen in explants from both normal (P < .001; P < .05) and IUGR (P < .05) pregnancies, MMP-2 release changed less in IUGR compared with normal explant cultures. There were no significant effects of oxygen on MMP-9 release. Conclusion: Placental explaints from IUGR pregnancies demonstrated reduced MMP-2, MMP-9, and TIMP-1 release compared with explants from normal pregnancies at high (20%) but not low (3%) oxygen.

Pregnancy among residents enrolled in general surgery: a nationwide survey of attitudes and experiences.

BACKGROUND Medical student interest in general surgery has declined, and the lack of adequate accommodation for pregnancy and parenting during residency training may be a deterrent. We explored resident and program director experiences with these issues in general surgery programs across Canada. METHODS Using a web-based tool, residents and program directors from 16 Canadian general surgery programs were surveyed regarding their attitudes toward and experiences with pregnancy during residency. RESULTS One hundred seventy-six of 600 residents and 8 of 16 program directors completed the survey (30% and 50% response rate, respectively). Multiple issues pertaining to pregnancy during surgical residency were reported including the lack of adequate policies for maternity/parenting, the major obstacles to breast-feeding, and the increased workload for fellow resident colleagues. All program directors reported the lack of a program-specific maternity/parenting policy. CONCLUSIONS General surgery programs lack program-specific maternity/parenting policies. Several issues have been highlighted in this study emphasizing the importance of creating and implementing such a policy.

Acute general surgery in Canada: a survey of current handover practices

BACKGROUND Todays acute care surgery (ACS) service model requires multiple handovers to incoming attending surgeons and residents. Our objectives were to investigate current handover practices in Canadian hospitals that have an ACS service and assess the quality of handover practices in place. METHODS We administered an electronic survey among ACS residents in 6 Canadian general surgery programs. RESULTS Resident handover of patient care occurs frequently and often not under ideal circumstances. Most residents spend less than 5 minutes preparing handovers. Clinical uncertainty owing to inadequate handover is most likely to occur during overnight and weekend coverage. Almost one-third of surveyed residents rate the overall quality of the handovers they received as poor. CONCLUSION Handover skills must be taught in a systematic fashion. Improved resident communication will likely decrease loss of patient information and therefore improve ACS patient safety.

Patterns and Trends in Immediate Postmastectomy Reconstruction in California: Complications and Unscheduled Readmissions.

Background: Immediate reconstruction rates after mastectomy are increasing but remain low. Little is known about hospital readmissions after these procedures. The authors studied unscheduled readmissions after immediate reconstruction. Methods: Using the Healthcare Cost and Utilization Project California State database, the authors identified patients undergoing mastectomy only or with immediate reconstruction for ductal carcinoma in situ and invasive breast cancer from 2005 to 2009. Immediate reconstruction included tissue expander/implant and autologous tissue reconstructions. The authors evaluated temporal trends in immediate reconstruction and factors associated with 30-day unscheduled readmissions after reconstruction. Results: The cohort contained 48,414 patients (mastectomy only, 35,648; immediate reconstruction, 12,766; tissue expander/implant, 10,437; autologous tissue, 2329). Readmission rates were not significantly different between mastectomy only and immediate reconstruction (3.55 percent versus 3.39 percent; p = 0.39); however, autologous tissue reconstruction was associated with a significantly higher readmission rate compared with tissue expander/implant reconstruction (4.08 percent versus 3.24 percent; p = 0.04). Conclusions: Immediate reconstruction does not result in higher readmission rates compared with mastectomy only. All women undergoing mastectomy should be offered consultation for reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Prevention and Management of Lymphedema after Breast Cancer Treatment

Lymphedema of the arm after breast cancer treatment continues to challenge clinicians worldwide. In this review, we examine the main modalities, both nonsurgical and surgical, to prevent and treat this as yet incurable condition.

Dietary alterations and restrictions following surgery for upper gastrointestinal cancers: Key components of a health-related quality of life intervention

PURPOSE The surgical treatment of upper gastrointestinal (GI) cancers, specifically esophageal and gastric cancers, often result in extensive health-related quality of life (HRQOL) concerns, particularly those associated with dietary adjustments. This paper provides a review of HRQOL changes following esophagectomy and gastrectomy, and describes key components of an intervention to improve dietary adjustments following surgery. METHODS Intervention development was informed by 1) current published evidence on HRQOL changes for patients following upper GI surgery, 2) examination of usual post-operative care related to dietary restrictions to identify areas for continued education and support and 3) the inclusion of a conceptual framework (the Chronic Care Model) to guide intervention design and inform the selection of appropriate outcome measures. RESULTS Three key components of an HRQOL intervention are identified, and should focus on HRQOL concerns associated with dietary alterations and restrictions following treatment, involve family caregivers, and be tailored and flexible to patient and family caregivers needs and preferences. CONCLUSIONS Evidence-based interventions to support long-term dietary alterations and restrictions following upper GI surgery are lacking, despite evidence confirming its impact on morbidity and mortality. Interventions are needed to support dietary adjustments, prevent malnutrition and excessive weight loss, and enhance HRQOL following surgery for upper GI cancers.