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Biomedical subjects

Catherine Farrell

Publications and source records attributed to Catherine Farrell.

8 recordsLinked to original sources
PubMed2006

National recommendations for donation after cardiocirculatory death in Canada: Donation after cardiocirculatory death in Canada.

These recommendations are the result of a national, multidisciplinary, year-long process to discuss whether and how to proceed with organ donation after cardiocirculatory death (DCD) in Canada. A national forum was held in February 2005 to discuss and develop recommendations on the principles, procedures and practice related to DCD, including ethical and legal considerations. At the forum's conclusion, a strong majority of participants supported proceeding with DCD programs in Canada. The forum also recognized the need to formulate and emphasize core values to guide the development of programs and protocols based on the medical, ethical and legal framework established at this meeting. Although end-of-life care should routinely include the opportunity to donate organs and tissues, the duty of care toward dying patients and their families remains the dominant priority of health care teams. The complexity and profound implications of death are recognized and should be respected, along with differing personal, ethnocultural and religious perspectives on death and donation. Decisions around withdrawal of life-sustaining therapies, management of the dying process and the determination of death by cardiocirculatory criteria should be separate from and independent of donation and transplant processes. The recommendations in this report are intended to guide individual programs, regional health authorities and jurisdictions in the development of DCD protocols. Programs will develop based on local leadership and advance planning that includes education and engagement of stakeholders, mechanisms to assure safety and quality and public information. We recommend that programs begin with controlled DCD within the intensive care unit where (after a consensual decision to withdraw life-sustaining therapy) death is anticipated, but has not yet occurred, and unhurried consent discussions can be held. Uncontrolled donation (where death has occurred after unanticipated cardiac arrest) should only be considered after a controlled DCD program is well established. Although we recommend that programs commence with kidney donation, regional transplant expertise may guide the inclusion of other organs. The impact of DCD, including pre-and post-mortem interventions, on donor family experiences, organ availability, graft function and recipient survival should be carefully documented and studied.

Canada↗
PubMed2006

The potential efficacy of omega-3 fatty acids as anti-angiogenic agents in benign vascular tumors of infancy.

Hemangiomas of infancy are benign vascular tumors frequently encountered in pediatrics. Medical treatment (corticosteroids, interferon, chemotherapy, embolization and radiation) in high-risk hemangioma cases could greatly benefit from the addition of new and safer therapies. The rapid growth of hemangiomas during the proliferative phase occurs secondary to a process of local uncontrolled angiogenesis, involving potent mediators such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). We hypothesize that omega-3 fatty acids, naturally occurring nutrients of proven health benefit to infants, could become an alternative or an adjuvant treatment for hemangiomas, by slowing down their rapid proliferation phase through anti-angiogenic and anti-tumoral effects. Suggested mechanisms of action of omega-3 fatty acids include the downregulation of VEGF and bFGF, and the suppression of pro-angiogenic eicosanoids such as cylooxygenase-2. In this article, we review recent animal and human studies using dietary omega-3 fatty acids supplements, alone or in conjunction with chemotherapy, for the treatment of a variety of tumors dependent on angiogenesis for growth. Available murine hemangioma models offer the opportunity to determine optimal omega-3 fatty acid dose, while taking in account related immunohistochemical markers, clinical outcome and secondary effects, before planning clinical trials. Lessons learned in hemangiomas of infancy may have a broad impact in understanding the phenomenon of dysregulated angiogenesis in cancer research.

Angiogenesis Inhibitors↗
PubMed2006

The moral experience of parents regarding life-support decisions for their critically-ill children: a preliminary study in France.

The common paediatric critical care practice in France is for physicians (rather than parents) to maintain the ultimate responsibility for lifesupport decisions in children. Some French literature asserts that it is inappropriate for parents to bear such responsibilities because they do not have the required knowledge and should be protected from feeling culpable for such decisions. The aim of this grounded theory preliminary study was to examine the moral experience of parents of critically-ill children that required life-support decisions in France. A convenience purposive sample of seven parents was recruited in Paris. Five principal themes emerged as significant from these interviews: (1) a need for more information; (2) physicians should be responsible for life-support decisions; (3) the child's concerns and wishes need to be better heard; (4) maternal guilt; and (5) physicians require better training in parent communication. These findings raise important issues for clinical practice and further research in France.

Adaptation, Psychological↗
PubMed2004

Elective cesarean delivery and long-term motor function or ambulation status in infants with meningomyelocele.

OBJECTIVE: To determine if elective cesarean delivery, when compared with trial of labor, is associated with better long-term motor function or ambulation status in infants with myelomeningocele. METHODS: This is a retrospective cohort study of patients with myelomeningocele followed at the Spinal Dysfunction Program at Alfred I. duPont Hospital for Children in Wilmington, Delaware. Medical records were reviewed for gestational age at delivery, birthweight, anatomical level of lesion, and initial (0-6 months) and long-term (10 years or longer) motor function. Ambulation status (independent ambulation, ambulant with assistance, or wheelchair-bound) at 2 and 10 years was compared with those delivered by elective cesarean versus those delivered after trial of labor. RESULTS: Of the 106 patients with myelomeningocele that were identified, 87 (82%) had all the data required for this review. There were 44 patients in the elective cesarean group and 43 in the trial of labor group. There was no significant difference in gestational age at delivery or birthweight between the groups. There was statistical difference between the 2 groups when anatomical, initial, and current motor levels were compared. Compared with the elective cesarean group, patients in the trial of labor group were more likely to be ambulatory at 2 years (independently ambulant 7% versus 28%, ambulant with assistance 63% versus 65%, or wheelchair-bound 30% versus 7%, P =.003) and at 10 years (independently ambulant 5% versus 21%, ambulant with assistance 30% versus 54%, or wheelchair-bound 65% versus 25%, P <.001). However, when logistic regression analysis was used to control for motor level of myelomeningocele, no significant association was observed in ambulatory status at ages 2 and 10 years between infants delivered by elective cesarean or after trial of labor. CONCLUSION: Elective cesarean delivery, when compared with delivery after trial of labor, was not associated with better motor function or ambulation status in myelomeningocele patients. LEVEL OF EVIDENCE: II-2

Adolescent↗
PubMed2003

Development of a scoring system for predicting the risk of preterm birth in women receiving cervical cerclage.

OBJECTIVE: To develop a model for identifying women receiving cervical cerclage at risk for spontaneous preterm birth <32 weeks. STUDY DESIGN: Retrospective cohort study of high-risk patients based on past obstetric history. Our inclusion criteria involved all patients with singleton gestation who received cerclage between 10 and 24 weeks. They were evaluated for the risk factors associated with preterm birth <32 weeks. Risk factors evaluated include: indication for cerclage, gestational age at cerclage placement, cervical length prior to cerclage, timing of cerclage (emergency or elective) and route of cerclage (abdominal or vaginal). Univariable and multivariable analyses were used to determine the risk factors associated with preterm birth. A risk-scoring model was developed for the prediction of preterm birth <32 weeks in women receiving cerclage. RESULTS: We identified 256 women receiving cerclage that met our inclusion criteria. Preterm births <32 weeks occurred in 51 (20%). Multivariable analysis revealed a cervical length <25 mm, a history of cone biopsy and emergency cerclage to be significant risk factors associated with preterm birth <32 weeks. The sensitivity, specificity, positive and negative predictive values of the best model for predicting spontaneous preterm birth <32 weeks in women with cerclage are 80%; 96%; 82% and 95%, respectively. CONCLUSION: The presence of a short cervical length, a history of cone biopsy and emergency cerclage were associated with preterm birth <32 weeks. Our model had a high sensitivity for identifying women who may benefit from a closer surveillance.

Adult↗
PubMed2002

The insulation of genes from external enhancers and silencing chromatin.

Insulators are DNA sequence elements that can serve in some cases as barriers to protect a gene against the encroachment of adjacent inactive condensed chromatin. Some insulators also can act as blocking elements to protect against the activating influence of distal enhancers associated with other genes. Although most of the insulators identified so far derive from Drosophila, they also are found in vertebrates. An insulator at the 5' end of the chicken beta-globin locus marks a boundary between an open chromatin domain and a region of constitutively condensed chromatin. Detailed analysis of this element shows that it possesses both enhancer blocking activity and the ability to screen reporter genes against position effects. Enhancer blocking is associated with binding of the protein CTCF; sites that bind CTCF are found at other critical points in the genome. Protection against position effects involves other properties that appear to be associated with control of histone acetylation and methylation. Insulators thus are complex elements that can help to preserve the independent function of genes embedded in a genome in which they are surrounded by regulatory signals they must ignore.

Animals↗
PubMed2002

Protection from thymic epithelial cell injury by keratinocyte growth factor: a new approach to improve thymic and peripheral T-cell reconstitution after bone marrow transplantation.

Decreased thymopoietic capacity contributes to the severe and clinically significant immune deficiency seen after bone marrow transplantation (BMT). One mechanism for thymopoietic failure is damage to the interleukin 7 (IL-7)-producing thymic epithelial cells (TECs) by irradiation and chemotherapy, which can be partially treated by IL-7 administration. Pretreatment of BMT recipients with keratinocyte growth factor (KGF, or Fgf7), an epithelial cell-specific growth factor, protects mucosal, cutaneous, and pulmonary epithelial cells from cytotoxic therapy-induced damage in experimental murine models. Like other epithelial cells, TECs specifically express KGF receptors. Because KGF specifically protects KGF receptor-bearing epithelial cells and post-BMT immune deficiency is caused by loss of TECs, we hypothesized that KGF pretreatment would improve post-BMT thymic function. To test the hypothesis, BMT recipient mice were given KGF or placebo prior to congenic or allogeneic BMT. Administration of KGF before murine BMT significantly increased the capacity of the thymus to generate donor-derived thymocytes. KGF pretreatment also normalized the proportion of thymic subpopulations, increased the number of naive T cells in the periphery, and improved the response to neoantigen immunization. KGF treatment caused increased production of intrathymic IL-7, and the thymopoietic effects of KGF required an intact IL-7 signaling pathway. These results demonstrate that KGF may have immunomodulatory effects by a unique mechanism of protection of TECs. Furthermore, thymic injury and prolonged posttransplantation immune deficiency in BMT recipients can be prevented by KGF administration.

Animals↗