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Biomedical subjects

P Gilmore

Publications and source records attributed to P Gilmore.

7 recordsLinked to original sources

Clinical and angiographic outcome in the laser angioplasty for restenotic stents (LARS) multicenter registry.

In-stent restenosis (ISR), when treated with balloon angioplasty (PTCA) alone, has an angiographic recurrence rate of 30%-85%. Ablating the hypertrophic neointimal tissue prior to PTCA is an attractive alternative, yet the late outcomes of such treatment have not been fully determined. This multicenter case control study assessed the angiographic and clinical outcomes of 157 consecutive procedures in 146 patients with ISR at nine institutions treated with either PTCA alone (n = 64) or excimer laser assisted coronary angioplasty (ELCA, n = 93)) for ISR. Demographics were similar except more unstable angina at presentation in ELCA-treated patients (74.5% vs. 63.5%; P = 0.141). Lesions selected for ELCA were longer (16.8 +/- 11.2 mm vs. 11.2 +/- 8.6 mm; P < 0.001), more complex (ACC/AHA type C: 35.1% vs. 13.6%; P < 0.001), and with compromised antegrade flow (TIMI flow < 3: 18.9% vs. 4.5%; P = 0.008) compared to PTCA-treated patients. ELCA-treated patients had similar rate of procedural success [93 (98.9% vs. 62 (98.4%); P = 1.0] and major clinical complications [1 (1.1%) vs. 1 (1.6%); P = 1.0]. At 30 days, repeat target site coronary intervention was lower in ELCA-treated patients (1.1% vs. 6.4% in PTCA-treated patients; P = 0.158), but not significantly so. At 1 year, ELCA-treated patients had similar rate of major cardiac events (39.1% vs. 45.2%; P = 0.456) and target lesion revascularization (30.0% vs. 32.3%; P = 0.646). These data suggest that ELCA in patients with complex in-stent restenosis is as safe and effective as balloon angioplasty alone. Despite higher lesion complexity in ELCA-treated patients, no increase in event rates was observed. Future studies should evaluate the relative benefit of ELCA over PTCA alone for the prevention of symptom recurrence specifically in patients with complex in-stent restenosis.

Aged↗

Uncovering BRCA1-regulated signalling pathways by microarray-based expression profiling.

The introduction of microarray technology to the scientific and medical communities has dramatically changed the way in which we now address basic biomedical questions. Expression profiling using microarrays facilitates an experimental approach where alterations in the transcript level of entire transcriptomes can be simultaneously assayed in response to defined stimuli. We have used microarray analysis to identify downstream transcriptional targets of the BRCA1 (Breast Cancer 1) tumour-suppressor gene as a means of defining its function. BRCA1 has been implicated in the predisposition to early onset breast and ovarian cancer and while its exact function remains to be defined, roles in DNA repair, cell-cycle control and transcriptional regulation have been implied. In the current study we have generated cell lines with tetracycline-regulated, inducible expression of BRCA1 as a tool to identify genes, which might represent important effectors of BRCA1 function. Oligonucleotide array-based expression profiling identified a number of genes that were upregulated at various times following inducible expression of BRCA1 including the DNA damage-responsive gene GADD45 (Growth Arrest after DNA Damage). Identified targets were confirmed by Northern blot analysis and their functional significance as BRCA1 targets examined.

BRCA1 Protein↗

Increased expression of the RIalpha subunit of the cAMP-dependent protein kinase A is associated with advanced stage ovarian cancer.

The primary element in the cAMP signal transduction pathway is the cAMP-dependent protein kinase (PKA). Expression of the RIalpha subunit of type I PKA is elevated in a variety of human tumours and cancer cell lines. The purpose of this study was to assess the prognostic importance of RIalpha expression in patients with ovarian cancer. We have evaluated the expression of RIalpha in a panel of human ovarian tumours (n = 40) and five human ovarian cancer cell lines using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The human ovarian cell lines OAW42 and OTN14 express high endogenous levels of RIalpha mRNA and protein (at significantly higher mRNA levels than high tissue expressors, P < 0.05). The ovarian cell line A2780 expresses low endogenous levels of RIalpha mRNA and protein (also at higher mRNA levels than low tissue expressors, P < 0.05). Quantitative RT-PCR revealed no significant difference in RIalpha mRNA expression between different ovarian histological subtypes in this study. No associations were found between RIalpha mRNA expression and differentiation state. RIalpha mRNA expression was significantly associated with tumour stage (P = 0.0036), and this remained significant in univariate analysis (P = 0.0002). A trend emerged between RIalpha mRNA expression levels and overall survival in univariate analysis (P = 0.051), however, by multivariate analysis, stage remained the major determinant of overall survival (P = 0.0001). This study indicates that in ovarian epithelial tumours high RIalpha mRNA expression is associated with advanced stage disease. RIalpha expression may be of predictive value in ovarian cancer and may be associated with dysfunctional signalling pathways in this cancer type.

Adenocarcinoma, Clear Cell↗

Laser wire for crossing chronic total occlusions: "learning phase" results from the U.S. TOTAL trial. Total Occlusion Trial With Angioplasty by Using a Laser Wire.

The Prima laser guidewire system (Spectranectics Corp., Colorado Springs, CO) consists of an 0.018" hypotube containing a bundle of 45-microm optical fibers coupled to a pulsed excimer laser operating at a tip fluence of 60 ml/mm2 and a repetition rate ranging from 25-40 Hz. This laser guidewire was specifically designed to cross total occlusions refractory to passage with conventional wires. The Prima wire was evaluated in a feasibility study at 15 U.S. centers. Following failure to cross a total occlusion with approved guidewires, the Prima wire was utilized in 179 patients. Average age of subjects was 61 yr. Lesion locations included left anterior descending (36%), right (45%), and circumflex (19%) coronary arteries. Mean angiographic age of total occlusions was 70 wk (range, 2-1,020 wk, median, 14 wk). The use of the Prima wire either solely or in combination with conventional guidewires resulted in successful crossing in 61% of these previously impenetrable occlusions. Failure of the device was commonly related to length of the occlusion and tortuosity along the occluded pathway. Major complications included myocardial infarction in 7 patients (3.9%), tamponade in 3 (1.7%), and death in 2 (1.1%). This "learning phase" pilot study confirmed the feasibility of a laser guidewire in chronic total occlusions that are resistant to passage of conventional guidewires. An extended registry at these investigative sites is planned.

Adult↗

An unusual case of Reiter's disease.

A 72-year-old man was admitted to hospital after a syncopal attack. Investigations showed anaemia and adenocarcinoma of the colon. After tumour resection with end to end anastomosis he had a urinary catheter in situ for two days, but otherwise his recovery was unremarkable, until 13 weeks after operation when he developed classical Reiter's disease. Investigations did not reveal any known trigger factor but it is postulated that the process may have been initiated by urinary catheterisation or bowel surgery.

Adenocarcinoma↗