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Biomedical subjects

M Feneley

Publications and source records attributed to M Feneley.

15 recordsLinked to original sources
PubMed2006

Allelic imbalance and biochemical outcome after radical prostatectomy.

OBJECTIVE: To compare the incidence of allelic imbalance (AI) in men with rapid disease progression with those who remained disease free after radical prostatectomy, with the aim of identifying genetic markers to predict prognosis and guide further treatment. PATIENTS AND METHODS: Tumour and normal DNA were extracted from two matched groups of 31 men with extracapsular node-negative (pT3N0) prostate cancer who had undergone radical prostatectomy. One group comprised men who developed biochemical recurrence within 2 years of surgery and one group were prostate-specific antigen (PSA) free for at least 3 years. Men were matched for Gleason grade, preoperative PSA and pathological stage. Analysis was performed by genotyping. RESULTS: Allelic imbalance was analysed using 30 markers, and was seen in at least one marker in 57 (92%) of the cases. Deletion at marker D10S211 (10p12.1) was significantly more common in the relapse group than the non-relapse group (35 vs 5%, P=0.03). CONCLUSIONS: This study demonstrates significant association between AI on chromosome 10 and biochemical progression after radical prostatectomy.

Adult↗
PubMed2000

Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5.

Heterozygous mutations in the cardiac homeobox gene, NKX2-5, underlie familial cases of atrial septal defect (ASD) with severe atrioventricular conduction block. In this study, mice heterozygous for Nkx2-5-null alleles were assessed for analogous defects. Although ASD occurred only rarely, atrial septal dysmorphogenesis was evident as increased frequencies of patent foramen ovale and septal aneurysm, and decreased length of the septum primum flap valve. These parameters were compounded by genetic background effects, and in the 129/Sv strain, septal dysmorphogenesis bordered on ASD in 17% of Nkx2-5 heterozygotes. In a proportion of neonatal heterozygotes, as well as in adults with ASD, we found that the size of the foramen ovale was significantly enlarged and altered in shape, potentially exposing the normally thin septum primum to excessive hemodynamic forces. Therefore, defective morphogenesis of the septum secundum may be one contributing factor in the generation of patent foramen ovale, septal aneurysm, and certain ASDs. Mild prolongation of P-R interval in females and an increased frequency of stenotic bicuspid aortic valves were also features of the Nkx2-5 heterozygous phenotype. Our data demonstrate that the complex effects of Nkx2-5 haploinsufficiency in mice are weaker but convergent with those in humans. As in the mouse, the phenotype of human NKX2-5 mutations may be modulated by interacting alleles.

Alleles↗
PubMed1998

Rapid onset and dissipation of left atrial spontaneous echo contrast during percutaneous balloon mitral valvotomy.

BACKGROUND: Thromboembolism after percutaneous balloon mitral valvotomy (PBMV) has been attributed to dislodement of preexisting thrombus during transseptal puncture and instrumentation of the left atrium. The occurrence of thromboembolic events after PBMV in the absence of demonstrable left atrial thrombus before PBMV suggests that thrombus might form during the procedure. Spontaneous echo contrast (SEC) is a swirling pattern of blood echogenicity that is a marker of blood stasis in the left atrium. Exacerbation of left atrial SEC during PBMV may be indicative of an increased thromboembolic risk. METHODS: Transesophageal echocardiography was performed during PBMV in 20 patients with mitral stenosis. Grades of severity of left atrial SEC [0 (nil) to 4+ (severe)] were allocated before and after each balloon inflation. RESULTS: Before PBMV, SEC was present in 17 patients. New SEC or increased severity of SEC was observed during 49 of 56 balloon inflations. SEC was unchanged after six deflations, decreased after 14 deflations, and disappeared after 36 deflations. The mean times to onset and dissipation of SEC after balloon inflation and deflation were 3.1+/-1.5 and 3.9+/-1.6 seconds, respectively. After successful PBMV, SEC was unchanged in three patients, decreased in one, and resolved in 13. CONCLUSIONS: SEC is a dynamic and acutely reversible phenomenon that is highly sensitive to changes in left atrial hemodynamic conditions. Left atrial blood stasis induced by balloon inflation may promote thrombogenesis during PBMV.

Adult↗
PubMed1997

Inhibition of red cell aggregation prevents spontaneous echocardiographic contrast formation in human blood.

BACKGROUND: Spontaneous echocardiographic contrast (SEC) is a pattern of blood echogenicity that has been attributed to ultrasonic backscatter from blood cell aggregates that form under low shear conditions. Patients with left atrial SEC have an increased thromboembolic risk. This study examined the role of red cell and platelet aggregates in the pathogenesis of SEC in human blood and the effects on SEC of antithrombotic therapy and red cell disaggregatory agents. METHODS AND RESULTS: Blood echogenicity was examined with the use of quantitative videodensitometry over a controlled range of flow velocities in an in vitro model characterized by nonlaminar flow conditions. One hundred ninety study samples were prepared from single fresh blood donations (40 to 120 mL) from 24 healthy volunteers and 11 patients. Whole blood echogenicity was unaltered by depletion of platelets, stimulation of platelet aggregation with adenosine diphosphate, or inhibition of platelet aggregation with aspirin. Low flow-related echogenicity increased with increasing hematocrit (P<.001) but was abolished when red cells were lysed selectively with saponin (P<.001). In the presence of red cells, low flow-related echogenicity increased with increasing fibrinogen concentration (P<.001) and with plasma paraproteins. Low flow-related echogenicity in whole blood was unaltered by heparin and warfarin but was reduced in a dose-dependent manner by dextran 40 (40 mg/mL, 70% reduction, P<.001) and poloxamer 188 (8 mg/mL, 47% reduction, P<.001), which inhibited red cell aggregation. CONCLUSIONS: These results support protein-mediated red cell aggregation as the mechanism of SEC in human blood. Inhibition of red cell aggregation, indexed by resolution of SEC, may provide an alternative to anticoagulant and antiplatelet therapy to reduce cardiac thromboembolic risk.

Adult↗
PubMed1996

The day-to-day variation (test-retest reliability) of residual urine measurement.

OBJECTIVE: To determine the variation in repeated measurements of post-void residual urine volume (PVR), determined by transabdominal ultrasonography (TAUS), within an individual over time (test-retest reliability). PATIENTS AND METHODS: Forty men with symptomatic benign prostatic hyperplasia and awaiting transurethral resection of the prostate were studied over 3 months. Each underwent TAUS to determine both pre- and post-micturition residual volumes on six occasions within the study period. RESULTS: Although one-third of the patients had approximately constant residual volumes (variation in range < 120 mL), two-thirds had wide intra-individual variations over time (variation in range 150-670 mL). The values were log transformed to give a normal distribution and subjected to analysis of variance; there was a wide variation between and also within individuals. The larger the mean PVR, the larger was the overall variation in time. For those with a mean PVR of < 100 mL, the variation was less marked and these patients showed a more consistent test-retest repeatability. CONCLUSIONS: Although the PVR determined by TAUS may be useful to indicate aspects of bladder dysfunction or outlet obstruction, the wide variation in repeated measurements in the same individual limits its use for any clinical purpose that requires repeated assessment, e.g. in monitoring the response to treatment. There is poor test-retest reliability and PVRs cannot be determined reliably from a single measurement.

Aged↗
PubMed1990

Preventive strategies in management of acute myocardial infarction.

Recent studies on pathogenetic mechanisms, supplemented by findings in clinical trials point the way to a logical approach to acute evolving myocardial infarction. This is designed in the earliest stage to limit infarction through reduction in myocardial oxygen demands, improvement in collateral blood supply and dissolution of coronary thrombus, to prevent in a later stage coronary reocclusion through administration of antiplatelet agents, and then to prevent infarct expansion through reduction in ventricular wall tension throughout the period of repair. Application of such an approach holds the promise of reducing infarct size and all the complications of infarction, as well as short and long-term mortality. The approach is active and aggressive, and contrasts with the approach applied a decade ago, where infarction was accepted as inevitable and therapies were reserved for managing its complications.

Adrenergic beta-Antagonists↗
PubMed1989

Homograft aortic root replacement to correct infective endocarditis requiring seven open cardiac procedures.

Infective endocarditis, presumably from a septic dental focus, affecting the aortic valve was seen as acute aortic regurgitation in a 20-year-old woman. Seven open cardiac procedures for replacement of the aortic valve and left ventricular outflow tract were performed over the subsequent 6 years. Aortic root replacement using a fresh antibiotic-sterilized homograft was performed as the last definitive operative procedure. This article is presented to highlight (1) the use of homograft aortic root replacement for extensive involvement of aortic valve and left ventricular outflow tract in cases of infective endocarditis and (2) the feasibility of multiple sternal reentries when indicated.

Adult↗
PubMed1987

Mechanisms of the development and resolution of paradoxical interventricular septal motion after uncomplicated cardiac surgery.

Of 16 patients with normal preoperative left ventricular (LV) function studied by simultaneous two-dimensional and M-mode echocardiography before and after uncomplicated cardiac surgery, M-mode interventricular septal motion remained normal in seven (group I) and was paradoxical in nine (group II) 7 to 13 days postoperatively, but was normal in all 12 patients (7 group II) studied 3 to 18 months later. An abnormal systolic increase in normalized septal curvature, the essential feature of truly paradoxical septal motion, was not observed in either group during any study period (mean = 0.92 +/- 0.08), nor were significant differences found in septal thickening, LV fractional shortening, or fractional area change. In contrast, systolic anterior motion of the LV center increased from -0.1 +/- 1.6 mm preoperatively to 4.8 +/- 2.5 mm postoperatively in group II (p less than 0.001), and the LV posterior wall motion:thickening ratio increased from 1.10 +/- 0.33 to 2.16 +/- 0.45 (p less than 0.01), but both parameters had returned to preoperative levels at the follow-up study. Both parameters remained stable in group I during all study periods. In addition, direct intraoperative M-mode recordings (n = 14) demonstrated normal septal motion in both groups before chest closure, but esophageal echocardiograms (n = 10) demonstrated exaggerated anterior systolic LV motion within 2 hours of surgery in those from group II. Thus, early after uncomplicated cardiac surgery, apparently paradoxical septal motion relative to a fixed reference point is an artifact due to exaggerated cardiac mobility that resolves with the progressive restraining effect of postoperative adhesions.

Adult↗
PubMed1986

Effect of glyceryl trinitrate on peripheral arteries alters left ventricular hydraulic load in man.

Effects of sublingual glyceryl trinitrate (GTN) were studied in ten patients without heart failure during diagnostic cardiac catheterisation following angiography. GTN caused substantial reduction in peak left ventricular and aortic pressure (19 mmHg) with lesser reduction in mean aortic pressure (9 mmHg) and no change in diastolic aortic pressure. Reduction in stroke volume (by 15%), associated with fall in left ventricular end diastolic pressure (by 4 mmHg) was insufficient to explain the marked (17 mmHg - 34%) reduction in pulse pressure. Decrease in pulse pressure was associated with loss of the late systolic peak on both the aortic and left ventricular pressure wave. This peak is caused by pulse wave reflection. GTN caused no change in peripheral resistance or in indices of aortic compliance (characteristic impedance, total arterial compliance) but was associated with reduction in fluctuations of both modulus and phase of aortic impedance. All these changes in pressure waves and in impedance spectra are explicable on the basis of decreased peripheral wave reflection. This can be attributed to the known vasodilatory effect of GTN on the peripheral arteries. Simulation of arterial vasodilatation in a multi-branched model of the systemic arterial system confirmed this interpretation. Dilatation of peripheral arteries explains in part the beneficial effects of GTN in adult man.

Adult↗
PubMed1986

Paradoxical and pseudoparadoxical interventricular septal motion in patients with right ventricular volume overload.

Cross-sectional echocardiographic measurements of normalized septal curvature (NSC), systolic anterior motion of the center of the left ventricular cavity (CAM), and the M mode ratio of left ventricular posterior wall epicardial motion (PEM) to posterior wall thickening (PWT) were made in eight normal subjects, 16 patients with right ventricular volume overload (RVVO) and five with pressure overload (RVPO). Paradoxical M mode septal motion was confined to early systole in six patients with RVVO (group I) and was sustained in 10 (group II). Similar end-diastolic septal flattening was observed in RVVO group I (NSC 0.50 +/- 0.16 [SD]) and group II (0.49 +/- 0.23) when compared with the normal group (0.83 +/- 0.07, both p less than .005). NSC increased in both RVVO groups during the first one-third of systole (p less than .002) to values not significantly different from normal, but did not change significantly thereafter. CAM in RVVO group II (5.4 +/- 2.2 mm) exceeded CAM in both the normal group (1.8 +/- 1.9 mm, p less than .001) and group I (2.1 +/- 1.4 mm, p less than .005). Similarly, the PEM/PWT ratios in group II (mean 2.94; range 2.13 to 8.0) exceeded those in both the normal group (mean 1.59; range 1.11 to 2.13, p less than .01) and group I (mean 1.32; range 1.10 to 1.67, p less than .01). In the RVPO group, CAM was significant, the PEM/PWT ratios were lower than normal (p less than .01), and marked end-diastolic septal flattening was incompletely corrected during early systole, after which the septum was flattened further until end-systole (p less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Stratification of thromboembolic risk of atrial fibrillation by transthoracic echocardiography and transesophageal echocardiography: the relative role of left atrial appendage function, mitral valve disease, and spontaneous echocardiographic contrast.

The role of transesophageal echocardiography (TEE) in thromboembolic risk stratification in atrial fibrillation (AF) has not been established. Left atrial appendage contractile dysfunction in patients with AF predisposes to thrombus formation. The extent of blood stasis and propensity for thrombus can be assessed during TEE by measurement of the peak Doppler velocity of blood outflow from the appendage. Spontaneous echocardiographic contrast (SEC) is a swirling pattern of blood echogenicity that may be detected by TEE in the left atrium in patients with AF. The presence of SEC reflects left atrial blood stasis and a prothrombotic state. SEC is associated with an increased risk of systemic thromboembolic events. Parameters derived from TEE may provide additional prognostic data to clinical history and transthoracic echocardiography in thromboembolic risk stratification in AF.

Atrial Fibrillation↗