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Biomedical subjects

R A Walsh

Publications and source records attributed to R A Walsh.

At least 37 records · Page 2Linked to original sources
PubMed2000

Process measures in an antenatal smoking cessation trial: another part of the picture.

Data on provider and patient compliance can be crucial in understanding the degree of a health education program's effectiveness, as well as in identifying areas where the program requires modification. However, such data are rarely systematically reported in randomized trials. This report assesses the degree to which doctors and midwives complied with intervention protocols in a hospital antenatal smoking cessation trial, and also examines the program's acceptability to patients. Provider compliance was assessed principally via consultation audiotapes and provider-completed checklists. The audiotape analysis identified substantial compliance problems. For example, in relation to six specific smoking-related pregnancy risks, the proportions of Experimental Women informed about each individual risk ranged from 26 to 38% and the proportions receiving counselling items ranged from 52 to 79%. Doctors only informed a minority of Experimental Women of the increased risk of Sudden Infant Death Syndrome (28%) and of the presence of toxic chemicals in tobacco (21%). Comparison of compliance data from audiotapes and provider checklists revealed there was no significant agreement in three of four cases tested. Experimental Patients completed questionnaires to assess recall of smoking advice and to rate 12 program features. Of specific Experimental Program elements, the videotape (85%) received the highest level of positive patient ratings and the lottery (42%) the lowest. The process evaluation indicated that the Experimental Program needed some modification to increase its suitability for routine application. The findings also support the value of including an objective measure of provider compliance.

Female↗
PubMed2000

Influence of sarcoplasmic reticulum calcium loading on mechanical and relaxation restitution.

Mechanical and relaxation restitution represent the restoration of contractile force and relaxation, respectively, in premature beats having progressively longer extrasystolic intervals (ESI); these phenomena are related to intracellular activator Ca(2+) by poorly defined mechanisms. We tested the hypothesis that the level of phospholamban [which modulates the affinity of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase for Ca(2+), and thus the SR Ca(2+) load] may be an important determinant of both mechanical and relaxation restitution. Five mice with ablation of the phospholamban (PLB) gene (PLBKO), eight isogenic wild-type controls (129SvJ), eleven mice with PLB overexpression (PLBOE), and nine isogenic wild-type (FVB/N) controls were anesthetized and instrumented with a 1.4-Fr Millar catheter in the left ventricle and a 1-Fr pacemaker in the right atrium. At a cycle length of 200 ms, extrastimuli with increasing ESI were introduced, and the peak rates of left ventricular isovolumic contraction (+/-dP/dt(max)) were normalized and fit to monoexponential equations. In a subset, the protocols were repeated after ryanodine (4 ng/g) was administered to deplete SR Ca(2+) stores. The time constant of mechanical restitution in PLBKO was significantly shorter [6.3 +/- 1.2 (SE) vs. 47.7 +/- 7.6 ms] and began earlier (50 +/- 10 vs. 70 +/- 19 ms) than in 129SvJ. In contrast, the time constant of mechnical restitution was significantly longer (80.3 +/- 7.6 vs. 54.1 +/- 9.2 ms) in PLBOE than in FVB/N. The time constant of relaxation restitution was less in PLBKO than in 129SvJ (26.2 +/- 9.9 vs. 44.6 +/- 3.3, P < 0.05) but was similar in PLBOE and FVB/N (21.1 +/- 6.3 vs. 20.5 +/- 5.7 ms). Intravenous ryanodine decreased significantly the time constants of mechanical restitution in PLBOE, 129SvJ, and FVB/N but was lethal in PLBKO. In contrast, ryanodine increased the time constant of relaxation restitution. Thus 1) the phospholamban level is a critical determinant of mechanical restitution and (to a lesser extent) relaxation restitution in these transgenic models, and 2) ryanodine differentially affects mechanical and relaxation restitution. Furthermore, our data suggest a dissociation of processes within the SR that govern contraction and relaxation.

Animals↗
PubMed2000

Role of bacterial association and penetration on destruction of Escherichia coli O157:H7 in beef tissue by high pH.

This study was undertaken to determine if association with collagen enables Escherichia coli O157:H7 to resist high-pH treatments and to determine the effects of high pH on the survival of E. coli O157:H7 within different layers of beef tissue. E. coli O157:H7 was inoculated onto purified bovine type I collagen on 12-mm2 circular glass coverslips, plain 12-mm2 circular glass coverslips (control), and 12-mm2 irradiated (cobalt-60) lean beef tissue. The rates of destruction of E. coli O157:H7 inoculated on coverslips in pH 10.5 NaHCO3-NaOH buffer at 35 degrees C were determined at various sampling times. E. coli O157:H7 cells associated with collagen and treated in the same manner were also examined using scanning electron microscopy to determine if association with collagen enabled the organism to resist high-pH treatments. The inoculated tissue was treated in pH 13.0 NaHCO3-NaOH buffer at 25 degrees C, and penetrating cells of E. coli O157:H7 were recovered using a cryostat technique. There was no significant difference (P < 0.05) between the rates of destruction of collagen-associated E. coli O157:H7 and non-collagen-associated E. coli O157:H7 following exposure to high-pH treatments. Scanning electron micrographs showed that collagen-associated E. coli O157:H7 cells appeared physically damaged by exposure to high-pH treatments, and association of E. coli O157:H7 to collagen did not increase the resistance of the organism to destruction by high-pH rinses. No significant differences were seen between 20 ml of NaHCO3-NaOH buffer at pH 13.0 (treatment) and 20 ml of distilled water at pH 7.0 (control) when E. coli O157:H7 cells were recovered in beef tissue at depths of up to 2,000 microm (P < 0.05). The ability of E. coli O157:H7 to penetrate beef tissue may be an important factor in reducing the effectiveness of high-pH treatments in killing this organism on beef tissue. This finding should be considered in the future when designing treatments to decontaminate beef carcasses.

Animals↗
PubMed2000

Single scrotal incision orchiopexy for the palpable undescended testicle.

PURPOSE: We prospectively evaluated the Bianchi single high scrotal incision technique for orchiopexy in boys with palpable undescended testis distal to the external inguinal ring. MATERIALS AND METHODS: A total of 60 Bianchi orchiopexies were performed in 48 patients. We identified a group with primary undescended and secondary ascended testis, and a trapped testicle associated with previous inguinal surgery, respectively. Testicular position and size were assessed at 6 weeks of followup. RESULTS: We evaluated group 1-34 patients with bilateral (8), right (17) and left (9) primary undescended testis, group 2-3 with secondary ascended testis and group 3-11 with bilateral (4), right (4) and left (3) trapped testis. Average surgical time was 15, 35 and 35 minutes, respectively. Four patients required conversion to a traditional inguinal incision to achieve adequate cord length. All but 2 patients had a palpable testicle of acceptable size compared with the contralateral mate in the dependent scrotum at the end of the operation and 6 weeks postoperatively. Those returning for 1-year followup had identical findings. In groups 1 and 2 a single testicle normal to palpation resided in a high scrotal position and 1 testis required secondary orchiectomy for infarction, respectively. Scrotal hematoma resolved spontaneously without injury to the testis in 1 case. No hernias were evident. CONCLUSIONS: A single high scrotal incision for palpable primary, secondary ascended or even trapped testis is well tolerated, cosmetically pleasing and associated with a short operative time. The complication rate is acceptably low.

Child, Preschool↗
PubMed1999

Responses of cardiac protein kinase C isoforms to distinct pathological stimuli are differentially regulated.

Currently at least 11 protein kinase C (PKC) isoforms have been identified and may play different roles in cell signaling pathways leading to changes in cardiac contractility, the hypertrophic response, and tolerance to myocardial ischemia. The purpose of the present study was to test the hypothesis that responses of individual PKC isoforms to distinct pathological stimuli were differentially regulated in the adult guinea pig heart. Isolated hearts were perfused by the Langendorff method and were exposed to ischemia, hypoxia, H(2)O(2), or angiotensin II. Hypoxia and ischemia induced translocation of PKC isoforms alpha, beta(2), gamma, and zeta, and H(2)O(2) translocated PKC isoforms alpha, beta(2), and zeta. Angiotensin II produced translocation of alpha, beta(2), epsilon, gamma, and zeta isoforms. Inhibition of phospholipase C with tricyclodecan-9-yl-xanthogenate (D609) blocked hypoxia-induced (alpha, beta(2), and zeta) and angiotensin II-induced (alpha, beta(2), gamma, and zeta) translocation of PKC isoforms. Inhibition of tyrosine kinase with genistein blocked translocation of PKC isoforms by hypoxia (beta(2) and zeta) and by angiotensin II (beta(2)). By contrast, neither D609 nor genistein blocked H(2)O(2)-induced translocation of any PKC isoform. We conclude that hypoxia-induced activation of PKC isoforms is mediated through pathways involving phospholipase C and tyrosine kinase, but oxidative stress may activate PKC isoforms independently of Galphaq-phospholipase C coupling and tyrosine kinase signaling. Because oxidative stress may directly activate PKC, and PKC activation appears to be involved in human heart failure, selective inhibition of the PKC isoforms may provide a novel therapeutic strategy for the prevention and treatment of this pathological process.

Angiotensin II↗
PubMed1999

Increased protein kinase C activity and expression of Ca2+-sensitive isoforms in the failing human heart.

BACKGROUND: Increased expression of Ca2+-sensitive protein kinase C (PKC) isoforms may be important markers of heart failure. Our aim was to determine the relative expression of PKC-beta1, -beta2, and -alpha in failed and nonfailed myocardium. METHODS AND RESULTS: Explanted hearts of patients in whom dilated cardiomyopathy or ischemic cardiomyopathy was diagnosed were examined for PKC isoform content by Western blot, immunohistochemistry, enzymatic activity, and in situ hybridization and compared with nonfailed left ventricle. Quantitative immunoblotting revealed significant increases of >40% in PKC-beta1 (P<0.05) and -beta2 (P<0.04) membrane expression in failed hearts compared with nonfailed; PKC-alpha expression was significantly elevated by 70% in membrane fractions (P<0.03). PKC-epsilon expression was not significantly changed. In failed left ventricle, PKC-beta1 and -beta2 immunostaining was intense throughout myocytes, compared with slight, scattered staining in nonfailed myocytes. PKC-alpha immunostaining was also more evident in cardiomyocytes from failed hearts with staining primarily localized to intercalated disks. In situ hybridization revealed increased PKC-beta1 and -beta2 mRNA expression in cardiomyocytes of failed heart tissue. PKC activity was significantly increased in membrane fractions from failed hearts compared with nonfailed (1021+/-189 versus 261+/-89 pmol. mg-1. min-1, P<0.01). LY333531, a selective PKC-beta inhibitor, significantly decreased PKC activity in membrane fractions from failed hearts by 209 pmol. min-1. mg-1 (versus 42.5 pmol. min-1. mg-1 in nonfailed, P<0.04), indicating a greater contribution of PKC-beta to total PKC activity in failed hearts. CONCLUSIONS: In failed human heart, PKC-beta1 and -beta2 expression and contribution to total PKC activity are significantly increased. This may signal a role for Ca2+-sensitive PKC isoforms in cardiac mechanisms involved in heart failure.

Adolescent↗
PubMed1999

Influence of transgenic overexpression of phospholamban on postextrasystolic potentiation.

Twelve mice with PLB overexpression (PLBOE), and 11 isogenic FVB/N wild-type (WT) controls, were anesthetized and instrumented with a 1.4 F Millar catheter in the LV and a 1 F pacemaker in the right atrium. At a cycle length of 200 ms and a fixed extrastimulus of 120 ms, extrastimuli with increasing intervals (PESI) up to 1000 ms were introduced, and the peak rates of LV isovolumic contraction (+/- dP/dtmax) were normalized and fit to monoexponential equations. In a subset of animals, the protocols were repeated after ryanodine (4 ng/g) was given to deplete SR Ca2+ stores. The time constant and the plateau of the exponential curve fits were significantly greater in PLBOE than WT (107.8 +/- 7.0 v 75.2 +/- 5.5 ms and 1.39 +/- 0.03 v 1.08 +/- 0.02, both P < 0.05). At 200, 600 and 1000 ms, the normalized dP/dt was significantly greater in PLBOE than WT. After ryanodine, normalized dP/dt was significantly decreased in PLBOE, but unchanged in WT. The protein levels of the sodium-calcium exchanger normalized to calsequestrin were increased 3.7 +/- 0.3-fold in PLBOE compared to controls. In conclusion, the phospholamban level is a critical determinant of postextrasystolic potentiation in this transgenic model, and is differentially impaired by ryanodine at long diastolic intervals in PLBOE v controls. These differences may be due in part to changes in the protein level and resultant activity of the sodium calcium exchanger.

Adenosine Triphosphatases↗
PubMed1999

The effects of levosimendan on the left ventricular function and protein phosphorylation in post-ischemic guinea pig hearts.

The widely accepted theories for the decreased function in the stunned myocardium relate to Ca2+ desensitization and free radical-mediated tissue damage of the myofilaments. The aim of the present study was to examine whether the depressed contractile function and Ca2+ responsiveness of the stunned myocardium may be restored by a new Ca2+ sensitizer (levosimendan), which has been shown to improve the Ca2+ response of the myofilaments. The effects of levosimendan on the left ventricular function and the in vivo protein phosphorylation were examined in both the non-ischemic and the stunned myocardium. Myocardial stunning was induced in Langendorff-perfused guinea pig hearts by suspending the circulation for 8 min, followed by a 20-min reperfusion period. Perfusion of post-ischemic guinea pig hearts with levosimendan (0.03-0.48 microM, 6 min) was associated with dose- and time-dependent increases in both dP/dtmax (contractility) and dP/dtmin (speed of relaxation). When the effectiveness of levosimendan was compared in non-ischemic and post-ischemic hearts, no significant differences were noted in the relative stimulatory effects on contractility and relaxation, at any given time point (time-response curve) or concentration (dose-response curve). Perfusion of the guinea pig hearts with a high (0.3 microM) levosimendan concentration did not reveal any qualitative or quantitative difference in the phosphodiesterase inhibitory potential of the compound (elevation of tissue cyclic AMP levels and characteristics of protein phosphorylation) between the non-ischemic and the post-ischemic myocardium. However, when isoproterenol was administered to induce maximal in vivo phosphorylation of cardiac phosphoproteins, an attenuation of the 32P-incorporation into troponin I was noted in the post-ischemic hearts. The decrease in isoproterenol-induced 32P-incorporation into troponin I was associated with similar alterations in the tissue level of this protein. We conclude that the Ca2+ sensitizer levosimendan exerts dose- and time-dependent positive inotropic and lusitropic effects on the post-ischemic myocardium, lending support to the hypothesis tha Ca2+ desensitization of the myofibrils is involved in myocardial stunning.

Animals↗
PubMed1999

Prediction of human transplantation arteriopathy and coronary events with lung/heart count ratios during intravenous dipyridamole thallium-201 imaging.

BACKGROUND: Cardiac allograft arteriopathy often limits long-term survival in transplantation recipients but has been difficult to detect by standard diagnostic methods. Because of the diffuse nature of transplantation coronary disease, we postulated that a lung/heart ratio during dipyridamole thallium imaging might better predict arteriopathy-related complications than diagnostic methods that detect discrete luminal stenoses. METHODS AND RESULTS: Sixty-six unselected heart transplantation recipients were evaluated with annual coronary arteriograms, endomyocardial biopsy, and intravenous dipyridamole thallium testing (initial study group). The mean lung/heart ratio on an anterior planar image was 0.40 for all patients; therefore <0.40 was arbitrarily defined as normal. After October 1992, 98 patients were tested (validation study group) and a lung/heart ratio cutoff of 0.40 was evaluated prospectively. Coronary end points were defined as (1) at least 1 coronary artery stenosis >/=50% of the luminal diameter, (2) sudden cardiac death, and (3) acute myocardial infarction. Stepwise logistic regression analysis was performed to identify independent predictors of future coronary end points. For the initial study group, the lung/heart ratio on the first annual thallium study was the only independent predictor of subsequent cardiac end points (0.47 +/- 0.13 [SD] with end points vs 0.38 +/- 0.11 without end points, P <.05). For the validation study group, independent predictors of subsequent coronary events included the lung/heart ratio and the radionuclide left ventricular ejection fraction. No patient with a lung/heart ratio <0.40 and a left ventricular ejection fraction >/=0.50 developed a cardiac event during 21 +/- 11 months of follow-up. CONCLUSIONS: A lung/heart ratio >/=0.40 on dipyridamole thallium testing is a sensitive predictor of coronary events after heart transplantation. Patients with heart transplantion who have a lung/heart ratio <0.40 and normal systolic left ventricular function are at low risk for subsequent coronary events and may not require annual surveillance by coronary arteriography.

Coronary Disease↗
PubMed1999

Pathogenesis of dilated cardiomyopathy: molecular, structural, and population analyses in tropomodulin-overexpressing transgenic mice.

Dilated cardiomyopathy is characterized by decreased contractile function and loss of myofibril organization. Previously unexplored structural and molecular events that precede and initiate dilation can now be studied in tropomodulin-overexpressing transgenic (TOT) mice exhibiting progressive dilated cardiomyopathy. Onset of dilation did not correspond to a change in transgene expression levels, which were more than threefold above normal at birth and remained elevated throughout postnatal life. Similarly, mitogen-activated protein kinase activation (p38, ERK1/ERK2, JNK1/JNK2) was not associated with dilation. In contrast, calcineurin was activated before dilation, presumably due to doubling of intracellular diastolic calcium levels in TOT cardiomyocytes. Amplitude of systolic calcium transients was greatly increased as well, demonstrating the novel and unique calcium handling profile of TOT cardiomyocytes. Loss of myofibril organization was not apparent by confocal microscopy until over 1 week after birth, although neonatal sarcomeric abnormalities were revealed by ultrastructural analysis. Rapid postnatal increases in heart:body weight ratio at 1.5 weeks were followed by two waves of mortality between 2 and 3 weeks after birth coincident with maturational stress. Ultimately, TOT pathogenesis is a compensatory response to altered sarcomeric structure driven by calcineurin activation within days after birth, making TOTs an excellent paradigm for studying the role of calcium overload in dilated cardiomyopathy.

Animals↗
PubMed1999

Effect of congestive heart failure on in vivo canine aortic elastic properties.

OBJECTIVES: The aim of this study was to characterize fully in vivo aortic compliance over a wide range of passive distending pressures, and to study pharmacologically induced alterations in compliance using an intravascular ultrasound-based technique in the canine model of heart failure. BACKGROUND: Altered aortic compliance may influence considerably the function of the failing heart. Although some studies demonstrate that patients with heart failure have decreased aortic compliance, data from other studies are conflicting. METHODS: Aortic pressures and dimensions in seven dogs were determined both before and after pacing-induced congestive heart failure (CHF) using simultaneous micromanometer and intravascular ultrasound transducers. Decreases in aortic pressure were produced at baseline and after nitroprusside and dobutamine infusions. Inner and outer aortic circumferences were drawn at the lumen-intimal and media-adventitial borders. RESULTS: Aortic pressure-dimension (chamber) stiffness constants were greater after heart failure was produced (10.0+/-1.5 vs. 6.7+/-1.5, p < 0.05), but stress-strain stiffness (material) constants were similar (11.4+/-1.8 vs. 11.3+/-1.0, p=NS). Equivasodilating doses of nitroprusside and 10 microg/kg/min dobutamine decreased pressure-dimension stiffness constants after pacing-induced heart failure but not beforehand. The aortic wall thickness to diameter ratio was significantly greater in CHF than in the control condition (0.30+/-0.08 vs. 0.16+/-0.03, p < 0.01). CONCLUSIONS: Aortic compliance is decreased in this model of CHF, and this change is attributable primarily to vessel geometry rather than material properties. Equivasodilating doses of nitroprusside and equivalent doses of dobutamine increase aortic chamber compliance in dogs with CHF, but not in normal dogs. These data suggest that the beneficial effects of nitroprusside and dobutamine in CHF occur in part from improvement in aortic compliance.

Animals↗
PubMed1999

Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart.

It is well accepted that inhibition of the Na,K-ATPase in the heart, through effects on the Na/Ca exchanger, raises the intracellular Ca2+ concentration and strengthens cardiac contraction. However, the contribution that individual isoforms make to this calcium regulatory role is unknown. Assessing the phenotypes of mouse hearts with genetically reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly demonstrates different functional roles for these isoforms in vivo. Heterozygous alpha 2 hearts are hypercontractile as a result of increased calcium transients during the contractile cycle. In contrast, heterozygous alpha 1 hearts are hypocontractile. The different functional roles of these two isoforms are further demonstrated since inhibition of the alpha 2 isoform with ouabain increases the contractility of heterozygous alpha 1 hearts. These results definitively illustrate a specific role for the alpha 2 Na,K-ATPase isoform in Ca2+ signaling during cardiac contraction.

Animals↗
PubMed1999

Teaching medical students alcohol intervention skills: results of a controlled trial.

OBJECTIVE: To assess the relative effectiveness of videotape feedback and lecture methods for teaching alcohol brief intervention skills. DESIGN: In a controlled trial, two student blocks received a manual, lecture and demonstration about the principles and practice of brief alcohol intervention. In addition, experimental students made a 20-min videotape and participated in a 1.5-h small group feedback session. Prior to and after training, all students completed questionnaires and videotaped interviews with simulated patients. SETTING: Faculty of Medicine and Health Sciences of the University of Newcastle, Australia. SUBJECTS: Final-year medical students. RESULTS: Levels of alcohol-related knowledge, attitudes and interactional skills as well as general interactional skills were significantly improved after teaching. Alcohol-related interactional skills that were unsatisfactory at pretest reached satisfactory standards at post-test. An intergroup comparison of the improvement between pre- and post-teaching scores indicated that there was no significant difference in the effectiveness of the two methods. CONCLUSIONS: Training can improve medical student performance in alcohol intervention. Further research is required to examine the relative effectiveness of different teaching methods.

Adult↗
PubMed1999

Uptake of seven myocardial tracers during increased myocardial blood flow by dobutamine infusion.

RATIONALE AND OBJECTIVES: Direct comparison of myocardial perfusion tracers has been made difficult by variability in experimental models, and by a virtual absence of data comparing tracer uptake to myocardial blood flow under conditions of increased myocardial oxygen consumption, similar to what occurs with dynamic exercise. METHODS: Tracer uptake versus myocardial blood flow was evaluated for thallium-201 (201TI) and six technetium-99m (99mTc) myocardial-imaging agents in 24 open-chest canines with an occluded left-anterior descending coronary artery during dobutamine infusion. Data were fitted to the exponential model y = ax(1 - exp[-PSc/x]), where y is the tissue tracer/g normalized to normal (activity at 1 mL/minute/g) and x is the blood flow measured by the radioactive microsphere method. RESULTS: With dobutamine, myocardial tracer uptake was linear across a wide range of ischemic and hyperemic flows for each tracer. Based on the permeability surface area product, 201TI and 99mTc Q3 provided the best tracer estimate of myocardial blood flow (5.30+/-0.86 mL/minute/g, r = 0.91; 5.46+/-0.58 mL/minute/g, r = 0.94, respectively). Correlation coefficient (r) values for other tracers studied were 99mTc Q4 (r =0.93), 99mTc Q12 (r = 0.93), 99mTc sestamibi (r = 0.90), 99mTc tetrofosmin (r = 0.96), and 99mTc-N-Noet (r = 0.82). CONCLUSIONS: Of the 99mTc tracers examined under conditions of dobutamine-altered myocardial contractility, the myocardial uptake properties of 99mTc Q3 were most similar to those of 201TI.

Animals↗