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Biomedical subjects

M T Kearney

Publications and source records attributed to M T Kearney.

At least 19 recordsLinked to original sources

Effect of sericea lespedeza (Lespedeza cuneata) fed as hay, on natural and experimental Haemonchus contortus infections in lambs.

Parasitic infection is one of the leading economic constraints in small ruminant production. This problem is exacerbated as the resistance of nematode populations to chemical treatment (anthelmintics) becomes increasingly more common. Condensed tannin (CT) containing plants are being investigated as alternative solutions to address these problems. This investigation was conducted to evaluate the effect of the CT containing forage, Lespedeza cuneata (sericea lespedeza, SL) fed as hay, on Haemonchus contortus infection in sheep. Naturally and experimentally infected lambs were fed either SL or bermudagrass (BG, control) hay for 49 days. All lambs were fed BG hay for an additional 14 days. SL hay effectively reduced (67-98%) fecal egg count (FEC) during the time of feeding for both infection groups. FEC increased in both infection groups after SL feeding was stopped which indicated an effect on fecundity. SL hay feeding also reduced worm numbers, with more of an effect on reducing naturally infected worm burdens (67.2%) than on establishment of incoming larvae (26.1%). SL fed as hay may be more useful to remove existing worms than establishing worms. The decrease in FEC would have the benefit of reduced pasture contamination.

Animal Feed↗

Effect of fat distribution on endothelial-dependent and endothelial-independent vasodilatation in healthy humans.

AIM: The present study aims to explore the relationship between inflammatory cytokines, plasma lipids, insulin, blood pressure (BP), total adiposity/markers of fat distribution and endothelial function in healthy people across a wide range of body fatness. METHODS: Seventy-three healthy people (44 women; age range: 24-64 years) with body mass index (BMI) range of 18.6-73.1 kg/m2 were recruited. All participants underwent assessment of conduit artery endothelial-dependent vasodilatation by using flow-mediated vasodilatation (FMD) of the brachial artery and endothelial-independent vasodilatation to sublingual GTN. They had blood taken for measurement of plasma markers of glucose homeostasis (fasting insulin and glucose), systemic inflammation (interleukin-6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor-alpha receptor 2 (TNF-alpha R2)) and lipids (low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides). Morphometric assessment (waist circumference, BMI and waist-to-hip ratio (WHR)) and systolic and diastolic arterial pressure were also measured. RESULTS: Markers of total body fat/fat distribution (waist circumference, BMI and WHR), inflammation (IL-6, CRP and TNF-alpha R2), metabolism (fasting insulin, HDL, LDL and triglycerides) and BP (systolic and diastolic) correlated with FMD. Among these measurements, WHR was the only independent predictor of FMD (r2 = 0.30; p = 0.0001). CONCLUSIONS: WHR is an important marker of endothelial dysfunction in healthy people across a wide range of body fatness.

Adult↗

Real-time three-dimensional echocardiography: a novel technique to quantify global left ventricular mechanical dyssynchrony.

BACKGROUND: Left ventricular (LV) mechanical dyssynchrony (LVMD) has emerged as a therapeutic target using cardiac resynchronization therapy (CRT) in selected patients with chronic heart failure. Current methods used to evaluate LVMD are technically difficult and do not assess LVMD of the whole LV simultaneously. We developed and validated real-time 3D echocardiography (RT3DE) as a novel method to assess global LVMD. METHODS AND RESULTS: Eighty-nine healthy volunteers and 174 unselected patients referred for routine echocardiography underwent 2D echocardiography and RT3DE. RT3DE data sets provided time-volume analysis for global and segmental LV volumes. A systolic dyssynchrony index (SDI) was derived from the dispersion of time to minimum regional volume for all 16 LV segments. Healthy subjects and patients with normal LV systolic function had highly synchronized segmental function (SDI, 3.5+/-1.8% and 4.5+/-2.4%; P=0.7). SDI increased with worsening LV systolic function regardless of QRS duration (mild, 5.4+/-0.83%; moderate, 10.0+/-2%; severe LV dysfunction, 15.6+/-1%; P for trend <0.001). We found that 37% of patients with moderate to severe LV systolic dysfunction had significant dyssynchrony with normal QRS durations (SDI, 14.7+/-1.2%). Twenty-six patients underwent CRT. At long-term follow-up, responders demonstrated reverse remodeling after CRT with a significant reduction in SDI (16.9+/-1.1% to 6.9+/-1%; P<0.0001) and end-diastolic volume (196.6+/-17.3 to 132.1+/-13.5 mL; P<0.0001) associated with an increase in LV ejection fraction (17+/-2.2% to 31.6+/-2.9%; P<0.0001). CONCLUSIONS: RT3DE can quantify global LVMD in patients with and without QRS prolongation. RT3DE represents a novel technique to identify chronic heart failure patients who may otherwise not be considered for CRT.

Computer Systems↗

Predicting sudden death in patients with mild to moderate chronic heart failure.

OBJECTIVES: To explore the relation between non-invasive measures of cardiac function and sudden cardiac death, as well as the development and utility of an index integrating these variables to identify patients at increased risk of this mode of death. DESIGN: UK-HEART (United Kingdom-heart failure evaluation and assessment of risk trial) was a prospective study conducted between December 1993 and April 2000. The study was specifically designed to identify non-invasive markers of death and mode of death among patients with chronic heart failure. SETTING: 8 UK general hospitals. MAIN OUTCOME MEASURES: Death and mode of death. RESULTS: 553 patients aged a mean (SD) of 63 (10) years, in New York Heart Association functional class 2.3 (0.02), recruited prospectively. After 2365 patient-years' follow up, 201 patients had died (67 suddenly). Predictors of sudden death were greater cardiothoracic ratio, QRS dispersion, QT dispersion corrected for rate (QTc) across leads V1-V6 on the 12 lead ECG, and the presence of non-sustained ventricular tachycardia. The hazard ratio and 95% confidence intervals (CI) of sudden death for a 10% increase in cardiothoracic ratio was 1.43 (95% CI 1.20 to 1.71), for a 10% increase in QRS dispersion 1.11 (95% CI 1.04 to 1.19), for the presence of non-sustained ventricular tachycardia 2.03 (95% CI 1.27 to 3.25), and for a 10% increase in QTc dispersion across leads V1-V6 1.03 (95% CI 1.00 to 1.07) (all p < 0.04). An index derived from these four factors performed well in identifying patients specifically at increased risk of sudden death. CONCLUSIONS: Results show that an index derived from three widely available non-invasive investigations has the potential to identify ambulant patients with chronic heart failure at increased risk of sudden death. This predictive tool could be used to target more sophisticated investigations or interventions aimed at preventing sudden death.

Aged↗

Inspiratory muscle load and capacity in chronic heart failure.

BACKGROUND: Although breathlessness is common in chronic heart failure (CHF), the role of inspiratory muscle dysfunction remains unclear. We hypothesised that inspiratory muscle endurance, expressed as a function of endurance time (Tlim) adjusted for inspiratory muscle load and inspiratory muscle capacity, would be reduced in CHF. METHODS: Endurance was measured in 10 healthy controls and 10 patients with CHF using threshold loading at 40% maximal oesophageal pressure (Poes(max)). Oesophageal pressure-time product (PTPoes per cycle) and Poes(max) were used as indices of inspiratory muscle load and capacity, respectively. RESULTS: Although Poes(max) was slightly less in the CHF group (-117.7 (23.6) v -100.0 (18.3) cm H(2)O; 95% CI -37.5 to 2.2 cm H(2)O, p = 0.1), Tlim was greatly reduced (1800 v 306 (190) s; 95% CI 1368 to 1620 s, p<0.0001) and the observed PTPoes per cycle/Poes(max) was increased (0.13 (0.05) v 0.21 (0.04); 95% CI -0.11 to -0.03, p = 0.001). Most of this increased inspiratory muscle load was due to a maladaptive breathing pattern, with a reduction in expiratory time (3.0 (5.8) v 1.1 (0.3) s; 95% CI 0.3 to 3.5 s, p = 0.03) accompanied by an increased inspiratory time relative to total respiratory cycle (Ti/Ttot) (0.43 (0.14) v 0.62 (0.07); 95% CI -0.3 to -0.1, p = 0.001). However, log Tlim, which incorporates the higher inspiratory muscle load to capacity ratio caused by this altered breathing pattern, was >/=85% predicted in seven of 10 patients. CONCLUSIONS: Although a marked reduction in endurance time was observed in CHF, much of this reduction was explained by the increased inspiratory muscle load to capacity ratio, suggesting that the major contributor to task failure was a maladaptive breathing pattern rather than impaired inspiratory muscle endurance.

Aged↗

Equine cyathostome populations: accuracy of species composition estimations.

Historically, surveys of equine parasites either are not quantitative in regard to prevalence and intensities of cyathostome species, or if quantitative, are estimates based on the identification of a very small sample of the population. Commonly 100-200 worms are identified. In the current study cyathostomes from 10 ponies were counted and identified to species in subsets of approximately 200 worms each from 5% aliquots of the large intestine contents until all worms in the aliquot were examined. A mean of 10.9+/-4.3 species were identified by examining 200 cyathostomes from each animal. This number increased to 25.2+/-2.6 species when the 5% aliquots were totally examined, indicating that prevalence rates from species with low intensities are probably much greater than previous survey data indicate. A statistical model was used to determine how many worms need to be identified to give a 95% confidence level that all species present are identified.

Animals↗

Comparison of adhesion formation associated with Pro-Tack (US Surgical) versus a new mesh fixation device, Salute (ONUX Medical).

BACKGROUND: We evaluated efficacy and associated adhesion formation of an innovative mesh fixation device versus the helical tack device and analyzed two implantation techniques. METHODS: Six purpose-bred female hounds were evaluated in this 90-day survival study. Six 4-cm round patches of 1-mm thick DualMesh were fixed to the abdominal wall with either 10 Pro-Tack or 10 Salute constructs in each patch. Zero to 4 additional patches were implanted with only Salute constructs. RESULTS: Adhesion severity scores were significantly higher for middle left abdominal wall sites versus lower right and upper left sites. The adhesion dissection score was higher for group T (Pro-Tack) versus group S (Salute). CONCLUSION: No significant effects occurred with adhesion extent scores, but group T developed denser adhesions. The second analysis determined that no significant differences existed relevant to secondary Salute placement, although the total score approached significance (p < 0.09). Salute equipment was easier to handle and allowed repositioning of the patch during operation.

Animals↗

Pathophysiological implications of insulin resistance on vascular endothelial function.

BACKGROUND: Insulin resistance is a key component of the insulin resistance syndrome and is a crucially important metabolic abnormality in Type 2 diabetes. Insulin-resistant individuals are at significantly increased risk of cardiovascular disease, although the underlying mechanisms remain incompletely understood. The endothelium is thought to play a critical role in maintaining vascular homeostasis, a process dependent on the balance between the production of nitric oxide, superoxide and other vasoactive substances. Endothelial dysfunction has been demonstrated in insulin-resistant states in animals and humans and may represent an important early event in the development of atherosclerosis. Insulin resistance may be linked to endothelial dysfunction by a number of mechanisms, including disturbances of subcellular signalling pathways common to both insulin action and nitric oxide production. Other potential unifying links include the roles of oxidant stress, endothelin, the renin angiotensin system and the secretion of hormones and cytokines by adipose tissue. Lifestyle measures and drug therapies which improve insulin sensitivity and ameliorate endothelial dysfunction may be important in delaying the progression to overt cardiovascular disease in at risk individuals. METHODS: We conducted a literature search using Medline, restricted to articles published in the English language between 1966 and the present, and reviewed bibliographies of relevant articles. An initial search strategy employing combinations of the MeSH terms: insulin resistance; endothelium, vascular; insulin; nitric oxide or hyperinsulinaemia produced over 300 references. Focused searches using keywords relevant to the molecular aspects of endothelial function and insulin signalling, and lifestyle or pharmacological interventions relevant to insulin resistance or endothelial function, produced over 300 further references. Abstracts of all references were screened before selecting those relevant to this review.

Arteriosclerosis↗

Obesity, atherosclerosis and the vascular endothelium: mechanisms of reduced nitric oxide bioavailability in obese humans.

It is now well established that obesity is an independent risk factor for the development of coronary artery atherosclerosis. The maintenance of vascular homeostasis is critically dependent on the continued integrity of vascular endothelial cell function. A key early event in the development of atherosclerosis is thought to be endothelial cell dysfunction. A primary feature of endothelial cell dysfunction is the reduced bioavailability of the signalling molecule nitric oxide (NO), which has important anti atherogenic properties. Recent studies have produced persuasive evidence showing the presence of endothelial dysfunction in obese humans NO bioavailability is dependent on the balance between its production by a family of enzymes, the nitric oxide synthases, and its reaction with reactive oxygen species. The endothelial isoform (eNOS) is responsible for a significant amount of the NO produced in the vascular wall. NO production can be modulated in both physiological and pathophysiological settings, by regulation of the activity of eNOS at a transcriptional and post-transcriptional level, by substrate and co-factor provision and through calcium dependent and independent signalling pathways. The present review discusses general mechanisms of reduced NO bioavailability including factors determining production of both NO and reactive oxygen species. We then focus on the potential factors responsible for endothelial dysfunction in obesity and possible therapeutic interventions targetted at these abnormalities.

Arteriosclerosis↗

Effects of nitric oxide synthase inhibition on Basal function and the force-frequency relationship in the normal and failing human heart in vivo.

BACKGROUND: Nitric oxide (NO) exerts autocrine/paracrine effects on cardiac function, including alterations of the inotropic state. In vitro studies suggest that NO modulates the myocardial force-frequency relationship. Basal left ventricular (LV) contractility is depressed and the force-frequency relationship is blunted in human heart failure, and it is speculated that an increase in NO production is involved. METHODS AND RESULTS: We compared the effects of intracoronary NO synthase inhibition with N(G)-monomethyl-L-arginine (L-NMMA; 25 micromol/min) on basal LV function and the response to incremental atrial pacing in patients with dilated cardiomyopathy (n=11; mean age, 51 years) and in control subjects with atypical chest pain and normal cardiac function (n=7; mean age, 54 years). In controls, L-NMMA significantly reduced basal LV dP/dt(max) (from 1826 to 1578 mm Hg/s; P<0.002), but had no effect on heart rate, mean aortic pressure, or right atrial pressure. Pacing-induced increases in LV dP/dt(max) were unaltered by L-NMMA. In patients with dilated cardiomyopathy, L-NMMA had no effect on baseline LV dP/dt(max) (from 1313 to 1337 mm Hg/s; P=NS). The blunted pacing-induced rise in LV dP/dt(max) in these patients was unaltered by L-NMMA. CONCLUSION: Endogenous NO has a small baseline positive inotropic effect in the normal human heart, which is lost in heart failure patients. NO does not significantly influence the force-frequency relationship in either the normal or failing human heart in vivo. Because this study was performed in patients with moderate heart failure, whether the findings apply to subjects with more severe heart failure requires further investigation.

Adult↗

Viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management.

Viral infection of the heart is relatively common and usually of little consequence. It can, however, lead to substantial cardiac damage and severe acute heart failure. It can also evolve into the progressive syndrome of chronic heart failure. Recent studies have gone some way towards unravelling the complex mechanisms underlying the heart muscle damage that occurs after viral infection. These studies have lent support to both immune and viral mediated (independent of an immune response) cardiac damage. Acute myocarditis can present in various ways, and it may be a cause of sudden death in an otherwise healthy young adult. New treatments for viral heart disease are awaited. In the meanwhile, the haemodynamic support of patients with acute left ventricular failure caused by myocarditis should be aggressive, to allow for the possibility of spontaneous recovery. Contemporary trials of treatment in chronic heart failure secondary to dilated cardiomyopathy support the use of angiotensin converting enzyme inhibitors, beta adrenoceptor blockers, and spironolactone in such patients.

Acute Disease↗

Differences in susceptibility to gastrointestinal nematode infection between Angus and Brangus cattle in south Louisiana.

Breed susceptibility to nematode infection was evaluated in Angus (Bos taurus) and Brangus (B. indicus crossbreed) cattle. A cow-calf herd and a yearling replacement heifer herd were monitored during one grazing season. Calves were born in March and were weaned in October. Individual rectal fecal samples were collected monthly from the two herds and processed for fecal egg counts (FEC) and coprocultures. Cow and calf FEC increased from April, reaching maximum values during the summer. Angus cows and calves had significantly (p<0.05) greater FEC than Brangus cows and calves, and Haemonchus and Cooperia were the predominant genera. Replacement heifer FEC showed a similar pattern with maximum levels during late summer/fall, and Haemonchus was the predominant genus. No significant differences were seen between breeds, however, infection levels were consistently lower in Brangus heifers. Ostertagia was present in cows and heifers only in fall/winter, which is consistent with summer inhibition. The data suggested that cows were an important source of pasture contamination for their susceptible calves and that the Brangus breed was relatively more resistant to infection. The use of B. indicus crossbreeds may help in alleviating reliance on chemical control by reducing the rate of pasture contamination and subsequent infection losses.

Animals↗

An experimental evaluation of methods used to enumerate mucosal cyathostome larvae in ponies.

With the increased interest in equine cyathostomes it has become apparent that some evaluations of methods currently used to count the various larval stages which occur in the mucosa would be beneficial. Experiments were conducted to investigate the effects of fixation and storage of mucosal tissues at -20 C on the accuracy of counting these larvae. The accuracy of counting developing larvae within the mucosa by transmural illumination (TMI) and by artificial digestion (DIG) of the mucosa was also compared. The data indicate that fixation of digested mucosa in PBS-buffered 5% or 10% formalin did not effect the enumeration of either early hypobiotic L3 or larger developing L3 or L4. Although not optimal, counting these larvae by either TMI of DIG after freezing did not significantly differ from counts made on fresh tissues. Significant differences were also not seen between counts of developing larvae made by TMI or DIG. Because DIG must be used to count EL3 and small developing L3, it is possible that TMI is not necessary in heavily infected equids.

Animals↗