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Biomedical subjects

Mary Mulcahy

Publications and source records attributed to Mary Mulcahy.

8 recordsLinked to original sources
PubMed2005

Living donor liver transplant for malignancy.

Adult-to-adult living donor liver transplantation (ALDLT) is being increasingly utilized to treat patients with locally advanced hepatocellular carcinoma and cholangiocarcinoma who are not prioritized under the MELD allocation system. A single institution retrospective chart review examined ALDLTs performed for malignancy to identify indications, complications, and transplant outcome. Since 1997, 18 ALDLTs have been performed for malignancy as the primary indication. Thirteen patients were transplanted for HCC. The median survival following transplant was 18.6 months and four patients developed recurrent HCC. Five patients were transplanted for cholangiocarcinoma, with a 100% recurrence free survival at a mean follow up of 18 months among patients given neo-adjuvant chemoradiation. ALDLT can be safely performed for malignancy with an acceptable peri-operative mortality rate. However, HCC patients with large tumors experience a high rate of recurrence. The use of ALDLT for cholangiocarcinoma appears promising specifically in the context of neo-adjuvant therapy.

Adult↗
PubMed2005

The effect of catheter-directed CT angiography on yttrium-90 radioembolization treatment of hepatocellular carcinoma.

PURPOSE: Yttrium 90 radioembolization is a transcatheter therapy for unresectable hepatocellular carcinoma (HCC) that delivers internal radiation to tumors. In contrast to the usual method of lobar regional delivery, catheter-directed computed tomographic (CT) angiography was investigated as a potentially useful technique to evaluate the administration of segmental 90Y tumor radiation doses superselectively without significantly altering liver function or Child-Pugh classification. MATERIALS AND METHODS: Fourteen patients underwent 90Y therapy for unresectable HCC. After standard angiographic placement of a 3-F microcatheter in a segmental hepatic artery supplying the tumor, each patient underwent CT angiography with use of segmental hepatic artery injection of iodinated contrast agent to confirm segmental perfusion and delineate segmental liver volume. 90Y was later injected into the same segmental artery. Target dose was calculated according to infused 90Y activity and targeted hepatic volume with standard lobar volume (before CT angiography) versus segmental liver volume (after CT angiography). The Wilcoxon signed-rank test (alpha = 0.05) was used to compare the estimated 90Y dose before CT angiography with the actual 90Y dose after CT angiography, as well as changes in serum bilirubin level and Child-Pugh classification as a result of treatment. RESULTS: The mean estimated tumor dose before CT angiography (SD) was 100 Gy +/- 43 (range, 35-169 Gy). The mean actual tumor dose after CT angiography was 348 Gy +/- 204 (range, 105-857 Gy), which was significantly greater (P < .001). The mean bilirubin level before treatment was 1.0 mg/dL +/- 0.97 (range, 0.2-4.0 mg/dL), whereas the mean bilirubin level after treatment was 1.3 mg/dL +/- 0.85 (range, 0.5-3.8 mg/dL). This difference, although statistically significant (P = .03), was not clinically important. Thirteen of 14 patients had no change in Child-Pugh class. CONCLUSION: CT angiography can be used to delineate the blood supply and volume to a targeted hepatic segment, allowing superselective 90Y radioembolization. This approach significantly increases effective 90Y tumor radiation dose without clinically altering liver function or Child-Pugh class.

Adult↗
PubMed2005

The role of the neonatal intensive care nurse in decision-making: advocacy, involvement in ethical decisions and communication.

Neonatal intensive care unit (NICU) nurses are often faced with complex clinical and ethical problems. Little is known about the role of the NICU nurse in ethical decision-making, or processes that inform decision-making in this setting. The purpose of this study was to explore and describe nurses' perceptions of their role as patient advocate, clinical situations that cause them concern and the extent of their involvement in ethical decision-making. A combined quantitative and qualitative research design was used. A questionnaire was administered to nurses working in the NICU of the sole perinatal tertiary referral centre of Western Australia, Australia. Findings showed that NICU nurses saw their role in ethical decision-making primarily as advocating for the best interests of the infant and family, that they used clinical knowledge and experience to guide ethical decision-making, they were able to clearly articulate ethical problems and respond to them according to the clinical scenario and, while being primarily assertive in presenting their views, some nurses took a more passive approach. These findings support the need for development of a multidisciplinary model for ethical decision-making, where the view of all team members are considered.

Australia↗
PubMed2002

Pilot study of gemcitabine (10 mg/m(2) per min) and cisplatin.

PURPOSE: Gemcitabine and cisplatin are routinely used in combination. In this combination, gemcitabine at conventional doses of 1000-1500 mg/m(2) is delivered weekly as a 30-minute bolus. Laboratory data suggest that the synthesis of gemcitabine triphosphate is saturable, and that gemcitabine infused at a rate of 10 mg/m(2) per min optimizes accumulation of the triphosphate. Early clinical experience suggests that gemcitabine delivered by a more prolonged infusion is more myelosuppressive. In this pilot study, we wished to assess if full-dose gemcitabine when given with cisplatin could be delivered by this more prolonged infusion. METHODS: In this study, all patients received cisplatin 75 mg/m(2). All gemcitabine doses were delivered at 10 mg/m(2) per min. For the initial cohort (level 1) the gemcitabine dose was 800 mg/m(2) per min. Subsequent escalations were 1000 mg/m(2) per min (level 2), and 1250 mg/m(2) per min (levels 3 and 4). For the first three cohorts, patients received gemcitabine on days 1, 8, and 15 and cisplatin on day 15 on a 28-day cycle. Patients on level 4 received gemcitabine on days 1 and 8 and cisplatin on day 8 on a 21-day cycle. Dose omissions or delays (holds) were mandated for NCI CTC grade 3 or 4 granulocytopenia or grade 2-4 thrombocytopenia. RESULTS: Entered onto this dose-finding study were 23 patients (12 male, 11 female) with advanced solid tumors. Seven patients were treatment-naive. Six patients were treated on level 1, five each on levels 2 and 3 and seven on level 4. Patients received one to seven cycles of treatment. Myelosuppression-related dose holds occurred at all levels. First-cycle dose holds occurred in three of six, four of five, three of five and two of seven patients on successive levels. First-cycle grade 3 or 4 granulocytopenia/thrombocytopenia occurred in three patients on level 1, one patient on level 2, two patients on level 3 and three patients on level 4. There were no partial or complete responses. Four patients were removed for toxicity (three myelosuppression, one nephrotoxicity), one at physician discretion, and 15 with disease progression. Three patients stopped therapy with stable disease after 5-6 months. On level 3, three of five patients remained on therapy for 4 months or more, compared to only one patient on each of the other three levels. CONCLUSIONS Weekly gemcitabine 1250 mg/m(2), utilizing a 10 mg/m(2) per min infusion rate, can be delivered with cisplatin 75 mg/m(2) with tolerable toxicity. When used in combination with cisplatin, however, the benefit of this fixed dose rate infusion gemcitabine compared to standard bolus gemcitabine remains to be determined.

Adult↗
PubMed2002

Caspase proteolysis of the cohesin component RAD21 promotes apoptosis.

Caspases are a conserved family of proteases that play a critical role in the execution of apoptosis by cleaving key cellular proteins at Asp residues and modifying their function. Using an expression cloning strategy we recently developed, we isolated human RAD21/SCC1/MCD1 as a novel caspase substrate. RAD21 is a component of the cohesin complex that holds sister chromatids together during mitosis and repairs double-strand DNA breaks. Interestingly, RAD21 is cleaved by a caspase-like Esp1/separase at the onset of anaphase to trigger sister chromatid separation. Here, we demonstrate that human RAD21 is preferentially cleaved at Asp(279) by caspases-3 and -7 in vitro to generate two major proteolytic products of approximately 65 and 48 kDa. Moreover, we show that RAD21 is specifically proteolyzed by caspases into a similarly sized 65-kDa carboxyl-terminal product in cells undergoing apoptosis in response to diverse stimuli. We also demonstrate that caspase proteolysis of RAD21 precedes apoptotic chromatin condensation and has important functional consequences, viz. the partial removal of RAD21 from chromatin and the production of a proapoptotic carboxyl-terminal cleavage product that amplifies the cell death signal. Taken together, these findings point to an entirely novel function of RAD21 in the execution of apoptosis.

Apoptosis↗
PubMed2002

Molecular markers in prognosis of colorectal cancer and prediction of response to treatment.

Colorectal cancer is the third most common human malignancy. Direct observation and biopsy sampling by colonoscopy have provided unique opportunities to study the natural history of the disease. As a consequence, advances in the understanding of colorectal cancer pathogenesis have evolved more rapidly than with most other solid tumours. Numerous molecular events arising during the development of colorectal cancer have been sorted out over the past two decades. Despite these advances, predicting outcome and response to therapy is still a major challenge in the management of patients with colorectal cancer. Molecular and biochemical markers of colorectal cancer are greatly needed for diagnosis and prognosis as well as for the selection and monitoring of treatments. The purpose of this chapter is to provide a critical assessment of the usefulness of markers in the prognosis and prediction of response to treatment in colorectal cancer.

Antineoplastic Agents↗
PubMedDate not supplied

Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere): assessment of hepatic arterial embolization.

In Canada and Europe, yttrium-90 microspheres (TheraSphere); MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.

Aged↗