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Biomedical subjects

E A Barnes

Publications and source records attributed to E A Barnes.

14 recordsLinked to original sources
PubMed2001

Dosimetric evaluation of lung tumor immobilization using breath hold at deep inspiration.

PURPOSE: To examine the dosimetric benefit of self-gated radiotherapy at deep-inspiration breath hold (DIBH) in the treatment of patients with non-small-cell lung cancer (NSCLC). The relative contributions of tumor immobilization at breath hold (BH) and increased lung volume at deep inspiration (DI) in sparing high-dose lung irradiation (> or = 20 Gy) were examined. METHODS AND MATERIALS: Ten consecutive patients undergoing radiotherapy for Stage I-IIIB NSCLC who met the screening criteria were entered on this study. Patients were instructed to BH at DI without the use of external monitors or breath-holding devices (self-gating). Computed tomography (CT) scans of the thorax were performed during free breathing (FB) and DIBH. Fluoroscopy screened for reproducible tumor position throughout DIBH, and determined the maximum superior-inferior (SI) tumor motion during both FB and DIBH. Margins used to define the planning target volume (PTV) from the clinical target volume included 1 cm for setup error and organ motion, plus an additional SI margin for tumor motion, as determined from fluoroscopy. Three conformal treatment plans were then generated for each patient, one from the FB scan with FB PTV margins, a second from the DIBH scan with FB PTV margins, and a third from the DIBH scan with DIBH PTV margins. The percent of total lung volume receiving > or = 20 Gy (using a prescription dose of 70.9 Gy to isocenter) was determined for each plan. RESULTS: Self-gating at DIBH was possible for 8 of the 10 patients; 2 patients were excluded, because they were not able to perform a reproducible DIBH. For these 8 patients, the median BH time was 23 (range, 19-52) s. The mean percent of total lung volume receiving > or = 20 Gy under FB conditions (FB scan with FB PTV margins) was 12.8%. With increased lung volume alone (DIBH scan with FB PTV margins), this was reduced to 11.0%, tending toward a significant decrease in lung irradiation over FB (p = 0.086). With both increased lung volume and tumor immobilization (DIBH scan with DIBH PTV margins), the mean percent lung volume receiving > or = 20 Gy was further reduced to 8.8%, a significant decrease in lung irradiation compared to FB (p = 0.011). Furthermore, at DIBH, the additional benefit provided by tumor immobilization (i.e., using DIBH instead of FB PTV margins) was also significant (p = 0.006). The relative contributions of tumor immobilization and increased lung volume toward reducing the percent total lung volume receiving > or = 20 Gy were patient specific; however, all 8 of the patients analyzed showed a dosimetric benefit with this DIBH technique. CONCLUSION: Compared to FB conditions, at DIBH the mean reduction in percent lung volume receiving > or = 20 Gy was 14.3% with the increase in lung volume alone, 22.1% with tumor immobilization alone, and 32.5% with the combined effect. The dosimetric benefit seen at DIBH was patient specific, and due to both the increased lung volume seen at DI and the PTV margin reduction seen with tumor immobilization.

Aged↗
PubMed2001

Patched1 interacts with cyclin B1 to regulate cell cycle progression.

The initiation of mitosis requires the activation of M-phase promoting factor (MPF). MPF activation and its subcellular localization are dependent on the phosphorylation state of its components, cdc2 and cyclin B1. In a two-hybrid screen using a bait protein to mimic phosphorylated cyclin B1, we identified a novel interaction between cyclin B1 and patched1 (ptc1), a tumor suppressor associated with basal cell carcinoma (BCC). Ptc1 interacted specifically with constitutively phosphorylated cyclin B1 derivatives and was able to alter their normal subcellular localization. Furthermore, addition of the ptc1 ligand, sonic hedgehog (shh), disrupts this interaction and allows cyclin B1 to localize to the nucleus. Expression of ptc1 in 293T cells was inhibitory to cell proliferation; this inhibition could be relieved by coexpression of a cyclin B1 derivative that constitutively localizes to the nucleus and that could not interact with ptc1 due to phosphorylation-site mutations to ALA: In addition, we demonstrate that endogenous ptc1 and endogenous cyclin B1 interact in vivo. The findings reported here demonstrate that ptc1 participates in determining the subcellular localization of cyclin B1 and suggest a link between the tumor suppressor activity of ptc1 and the regulation of cell division. Thus, we propose that ptc1 participates in a G(2)/M checkpoint by regulating the localization of MPF.

Animals↗
PubMed2001

Pediatric dacryocystorhinostomy for nasolacrimal duct obstruction.

OBJECTIVE: To determine the outcome of pediatric dacryocystorhinostomy (DCR) for large mucoceles or for primary nasolacrimal duct obstruction unresponsive to multiple probings. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred thirty-four external dacryocystorhinostomies were performed in 121 children. METHODS: Clinical case notes were reviewed for a series of cases operated on at Moorfields Eye Hospital by specialist lacrimal surgeons between 1987 and 1999. MAIN OUTCOME MEASURES: Postoperative relief of presenting symptoms and signs and complications. RESULTS: Fifty-nine percent of admissions (75 of 127) were day cases, and the other 52 admissions were inpatient. Simultaneous bilateral surgery was performed in 7 of 121 (6%) children, all but one having day case admission, and sequential bilateral surgery in 6 of 121 (5%) cases. Silicone intubation was performed in 20% of operations, these generally being early in the series. Three children had Down syndrome, five had craniofacial anomalies, and two had systemic disorders. Mild postoperative cellulitis occurred in three cases, all of which settled without complication after systemic antibiotic therapy, and there was one case of suture granuloma. There were no cases of immediate postoperative complication in either the day case or the inpatient groups. Complete cure of symptoms was achieved in 96% and an improvement of symptoms (with mild persistence of epiphora under challenge) in five cases (4%). CONCLUSION: For surgeons experienced in pediatric lacrimal surgery, external DCR with sutured mucosal flaps can be accomplished through an 8-mm incision with no surface sutures and minimal scarring. Symptoms are improved in all cases and complete cure achieved in 96%, with no immediate postoperative complications and only few (3%) short-term complications. The surgery is amenable to day case management, without significant morbidity, and may be performed as a simultaneous bilateral procedure.

Adolescent↗
PubMed2000

Cyclin F regulates the nuclear localization of cyclin B1 through a cyclin-cyclin interaction.

The key regulator of G(2)-M transition of the cell cycle is M-phase promoting factor (MPF), a complex composed of cdc2 and a B-type cyclin. Cyclin B1 nuclear localization involves phosphorylation within a region called the cytoplasmic retention signal, which also contains a nuclear export signal. The mechanism of MPF nuclear localization remains unclear since it contains no functional nuclear localization signal (NLS). We exploited the yeast two-hybrid screen to find protein(s) potentially mediating localization of cyclin B1 and identified a novel interaction between cyclin B1 and cyclin F. We found that cdc2, cyclin B1 and cyclin F form a complex that exhibits histone H1 kinase activity. Cyclin B1 and cyclin F also colocalize through immunofluorescence studies. Additionally, deletion analysis revealed that each putative NLS of cyclin F is functional. Taken together, the data suggest that the NLS regions of cyclin F regulate cyclin B1 localization to the nucleus. The interaction between cyclin B1 and cyclin F represents the first example of direct cyclin-cyclin binding, and elucidates a novel mechanism that regulates MPF localization and function.

Animals↗
PubMed2000

Subglottic stenosis secondary to extramedullary hematopoiesis in a patient with postpolycythemia myeloid metaplasia.

BACKGROUND: Extramedullary hematopoiesis (EMH) is known to occur in myeloproliferative disorders and hemoglobinopathies and is usually seen in the spleen and liver. METHODS: We report the first case of EMH causing subglottic stenosis in a woman with postpolycythemia myeloid metaplasia (PPMM). A tracheotomy was performed to maintain the airway and local radiotherapy was given. RESULTS: Two months after the radiotherapy was completed laryngoscopy showed an unobstructed airway with no evidence of disease, and the patient was successfully decanulated. Magnetic resonance imaging 8 months after radiotherapy confirmed the absence of local disease. CONCLUSION: Consideration should be given to EMH as a possible cause of airway obstruction in the differential diagnosis of a patient with a history of PPMM.

Aged↗
PubMed2000

Communication between primary care physicians and radiation oncologists regarding patients with cancer treated with palliative radiotherapy.

PURPOSE: The purpose of this study was to assess the satisfaction and information needs of primary care physicians (PCPs) regarding communication with radiation oncologists (ROs), with respect to patients who receive palliative radiotherapy (RT). A selected objective was to evaluate the agreement between PCPs' expectations and the content of the RO letter sent after completion of RT. PCPs' knowledge of the role of palliative RT and their awareness of available patient support services were also determined. METHODS: The PCPs of patients discharged from the Cross Cancer Institute after receiving palliative RT were surveyed using a mail-out questionnaire. Questions regarding communication, RT knowledge, and awareness of support services were asked. The corresponding RO letter was reviewed. RESULTS: A total of 148 PCPs were identified and were mailed questionnaires, with 114 (77%) responding. Overall, 80% (87 of 109) of PCPs found the RO letter to be useful in patient management. However, there was poor (< 53%) agreement between PCPs' expectations and the actual content of the RO letter. Knowledge of the indications and effectiveness of palliative RT was limited, with PCPs obtaining a median score of 4 of a possible 8. Only 27% (31 of 114) of PCPs were aware of all five of the patient support services listed. CONCLUSION: Results show that although the majority of PCPs found the RO letter useful, they believed that the letter lacked important information while containing unnecessary details. Communication between PCPs and ROs needs improvement, especially considering that PCPs seem to have limited knowledge of palliative RT.

Adult↗
PubMed1998

Increasing survival in AIDS patients with cytomegalovirus retinitis treated with combination antiretroviral therapy including HIV protease inhibitors.

OBJECTIVE: To assess the effect of combination antiretroviral therapy including HIV protease inhibitors on the survival of patients with cytomegalovirus retinitis (CMVR). DESIGN AND PARTICIPANTS: A longitudinal study of patients with CMVR diagnosed between October 1992 and May 1996 and followed to May 1997. SETTING: UK National Health Service specialist HIV medicine department. OUTCOME MEASURE: Time to death from first diagnosis of CMVR. Data were censored on 31 May 1997. RESULTS: Data were available on 147 patients with CMVR. Median survival of CMVR patients before December 1995 was 256 days [95% confidence interval (CI), 197-315]. Following the introduction of protease inhibitors in December 1995 this rose to 555 days (95% CI, 351-759). By 31 May 1996 median survival for the entire group of patients alive with CMVR had risen to 720 days (95% CI, 551-889). The mean survival after CMVR diagnosis was 224 days (n=89; 95% CI, 186-261; 1-year survival, 16%) in those who took no further antiretroviral therapy, 353 days in those who took nucleoside reverse transcriptase inhibitors but no protease inhibitors (n=34; 95% CI, 289-418; 1 -year survival, 50%), and 914 days in those who took a protease inhibitor (n=24; 95% CI, 768-1059; 1-year survival, 83%; P < 0.0001). Multivariate analysis showed that the strongest independent predictor of improved survival was having ever received a protease inhibitor after CMVR (relative risk of death, 0.063; 95% CI, 0.027-0.149; P < 0.0001). CONCLUSIONS: The use of HIV protease inhibitors in combination antiretroviral therapy has been associated with a marked increase in the survival of patients with CMVR.

AIDS-Related Opportunistic Infections↗
PubMed1991

Expression of active secreted forms of human amyloid beta-protein precursor by recombinant baculovirus-infected insect cells.

Three alternatively spliced forms of the amyloid precursor protein (APP), APP-695, APP-751, and APP-770, were expressed in the baculovirus expression vector system. The recombinant proteins were secreted into the culture medium by infected insect cells, and APP molecules were detected in insect cells and medium 2 days after infection with the recombinant APP-baculoviruses. A partial sequence of the NH2 terminus of the secreted protein revealed identity with the native secreted protein and showed that the signal peptide was recognized and properly cleaved in insect cells. Purified secreted recombinant APP-751 comigrated with protease nexin 2 purified from platelets and fibroblasts. A 15-kDa COOH-terminal fragment of APP was also detected in cells infected with recombinant baculoviruses, suggesting that recombinant APP proteins were cleaved at the COOH-terminal end like native APP protein. Recombinant APP-751 and APP-770 formed complexes with epidermal growth factor-binding protein, whereas APP-695 did not. In addition, recombinant APP-751 and APP-770 inhibited trypsin and chymotrypsin activity, whereas APP-695 did not. Growth of a human fibroblast cell line, A-1, that required APP for complete growth, was restored upon addition of secreted recombinant APP-695 or APP-751. Thus, the appropriately sized, secreted recombinant APP proteins produced in this expression system are biologically active.

Amino Acid Sequence↗
PubMed1989

Characterization of a novel 66 kd subunit of mammalian neurofilaments.

A 66 kd protein, pl 5.4, was purified from the Triton-insoluble fraction of rat spinal cord. This protein formed 10 nm filaments in vitro. The 66 kd protein was unique, although it shared homology with the 70 kd neurofilament protein (NF-L) and vimentin. An antiserum (anti-66) specific to the 66 kd protein did not cross-react with any of the neurofilament triplet proteins. In the spinal cord, anti-66 intensely stained the axons of the anterior and lateral columns. However, afferents from dorsal root ganglia and the efferents from the motoneurons were negative. In the cerebellum, anti-66 intensely stained most axons. The 66 kd protein was readily detectable in homogenates of forebrain, cerebellum, brainstem, and spinal cord, but was found only in trace amounts in adult sciatic nerves and was not found in extraneural tissues. The 66 kd protein constituted 0.5% of total protein in the spinal cord, whereas NF-L constituted about 1.5%.

Amino Acid Sequence↗
PubMedDate not supplied

Fatigue in patients with advanced cancer: a review.

Fatigue is the most common symptom in patients with advanced cancer. It is a subjective sensation with physical, cognitive, and affective modes of expression. The etiology is often unclear, and multiple potential etiologic factors for fatigue may coexist. Assessing fatigue involves characterizing its severity, temporal features, exacerbating and relieving factors, associated distress, and impact on daily life. Potential factors contributing to fatigue are the cancer itself, cancer treatment, cancer or treatment complications, medications, and other physical and psychosocial conditions. Many fatigue assessment tools exist. Fatigue management involves specific (targeting potentially reversible causes of fatigue) and symptomatic (targeting symptoms because no obvious etiology or reversible cause for fatigue can be identified) intervention and treatment measures. Specific interventions include treating anemia or metabolic and endocrine abnormalities, as well as managing pain, insomnia, depression, and anxiety. Symptomatic treatment involves education, counseling, and pharmacologic, and nonpharmacologic measures. Pharmacologic agents that have been investigated for use in treating fatigue include corticosteroids, progestational agents, and psychostimulants. Agents that modulate cytokine activity are future treatment possibilities.

Anxiety↗