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Biomedical subjects

Patrick J Burke

Publications and source records attributed to Patrick J Burke.

5 recordsLinked to original sources
PubMed2006

Computed tomography evaluation of superior-segment facet-joint violation after pedicle instrumentation of the lumbar spine with a midline surgical approach.

STUDY DESIGN: Retrospective study. OBJECTIVES: To determine the frequency of pedicle screw violation of superior nonfused facet joints adjacent to the most cephalad pedicle screws after a midline approach for lumbar fusion. SUMMARY OF BACKGROUND DATA: Facet-joint violations have been evaluated in patients undergoing lumbar pedicle screw instrumentation and fusion with a Wiltse muscle-splitting approach, but not via the more common midline approach. METHODS: Between 1995 and 2003, 204 patients underwent this procedure. Computed tomography scans (within 1 year postsurgery) were evaluated independently for superior facet-joint violation. chi tests were used to examine bivariate associations of superior level facet-joint violation, patient age, construct level, diagnosis, and revision status for significance (P < or = 0.05). RESULTS: Superior-level facet-joint violation occurred in 24% of patients and 15% of screws, twice as often on the left side (P = 0.0396) than on the right, more frequently in single than in multiple-level procedures (P < 0.0001), and most frequently with the most cephalad screws at L5 (48%). We found no significant associations between violation rates and other designated parameters. CONCLUSION: The left side, single-level fusion, and most cephalad pedicle screws at L5 are targets for interventions to reduce pedicle violations in this procedure.

Adult↗
PubMed2004

Antiestrogen binding site and estrogen receptor mediate uptake and distribution of 4-hydroxytamoxifen-targeted doxorubicin-formaldehyde conjugate in breast cancer cells.

The anthracycline antitumor drug, doxorubicin (DOX), has long been used as a broad spectrum chemotherapeutic. The literature now documents the role of formaldehyde in the cytotoxic mechanism, and anthracycline-formaldehyde conjugates possess substantially enhanced activity in vitro and in vivo. We have recently reported the design, synthesis, and preliminary evaluation of a doxorubicin-formaldehyde conjugate targeted, via 4-hydroxytamoxifen, to the estrogen receptor (ER) and antiestrogen binding site (AEBS), which are commonly present in breast cancer cells. The lead targeted doxorubicin-formaldehyde conjugate, called DOX-TEG-TAM, was found to possess superior cell growth inhibition characteristics relative to clinical doxorubicin and an untargeted control conjugate, especially in ER-negative, multidrug resistant MCF-7/Adr cells. The enhanced activity in the absence of estrogen receptor raised the possibility that targeting was also mediated via AEBS. Fluorescence microscopy of an ER-negative, AEBS-positive cell line as a function of time showed initial DOX-TEG-TAM localization in cytosol, in contrast to initial DOX and untargeted doxorubicin-formaldehyde conjugate localization in the nucleus. DOX-TEG-TAM was taken up by four AEBS-positive cell lines to a greater extent than doxorubicin and an untargeted doxorubicin-formaldehyde conjugate. Of the four cell lines, three were ER negative. DOX-TEG-TAM uptake was inhibited in a dose-dependent manner by the presence of a competing AEBS ligand. DOX-TEG-TAM retains 60% of the affinity of 4-hydroxytamoxifen for AEBS. DOX-TEG-TAM was also taken up by the AEBS-negative, ER-positive cancer cell line Rtx-6; with these cells uptake was inhibited in a dose-dependent manner by the ER ligand, estradiol. The data support the hypothesis that uptake of 4-hydroxytamoxifen targeted doxorubicin-formaldehyde conjugate is mediated by both the antiestrogen binding site and estrogen receptor.

Antineoplastic Agents↗
PubMed2004

Design, synthesis, and biological evaluation of doxorubicin-formaldehyde conjugates targeted to breast cancer cells.

The anthracycline antitumor drug doxorubicin (DOX) has been utilized for decades as a broad-spectrum chemotherapeutic. Recent literature evidence documents the role of formaldehyde in the cytotoxic mechanism, and anthracycline-formaldehyde conjugates possess substantially enhanced activity in vitro and in vivo. Targeting a doxorubicin-formaldehyde conjugate specifically to cancer cells may provide a more efficacious chemotherapeutic. The design and 11-step synthesis of doxorubicin-formaldehyde conjugates targeted to the estrogen receptor, which is commonly overexpressed in breast cancer cells, are reported. The formaldehyde is incorporated in a masked form as an N-Mannich linkage between doxorubicin and salicylamide. The salicylamide triggering molecule, previously developed to release the doxorubicin-formaldehyde active metabolite, is tethered via derivatized ethylene glycols to an E and Z mixture of 4-hydroxytamoxifen. The targeting group, E/Z-4-hydroxytamoxifen, was selected for its ability to tightly bind the estrogen receptor and antiestrogen binding sites. The targeted doxorubicin-formaldehyde conjugates' estrogen receptor binding and in vitro growth inhibition were evaluated as a function of tether length. The lead compound, DOX-TEG-TAM, bearing a triethylene glycol tether, binds the estrogen receptor with a binding affinity of 2.5% relative to E/Z-4-hydroxytamoxifen and inhibits the growth of four breast cancer cell lines with 4-fold up to 140-fold enhanced activity relative to doxorubicin.

Antineoplastic Agents↗
PubMedDate not supplied

Human oocyte radiosensitivity.

The teratogenic effects of ionizing radiation are well documented, but less is known about the radiosensitivity of the human oocyte. Women of childbearing age are understandably concerned about diagnostic radiology examinations--their risk/benefit ratio and their impact on the ability to conceive. Current research and evidence gathered from studies of the long-term effects of intra-abdominal therapeutic radiation shed light on this subject. With respect to this issue, radiographers can now give more practical advice to their nongravid female patients.

Chromosome Aberrations↗