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Biomedical subjects

Lynne Williams

Publications and source records attributed to Lynne Williams.

9 recordsLinked to original sources
PubMed2006

Diastolic ventricular interaction: from physiology to clinical practice.

The ventricles share a common septum and, therefore, the filling of one influences the compliance of the other. This phenomenon is known as direct diastolic ventricular interaction. The interaction is noticeably increased when the force exerted by the surrounding pericardium is raised, which is termed pericardial constraint. In healthy individuals, pericardial constraint is minor in the resting state. When right ventricular volume-to-pressure ratio acutely increases, however, such as during exercise, massive pulmonary embolism, or right ventricular infarction, notable diastolic ventricular interaction occurs. In this setting, the measured left ventricular intracavitary diastolic pressure overestimates the true left ventricular filling pressure, because the effect of external forces must be subtracted. Although growth of the pericardium can be a feature of chronic cardiac enlargement, here we review the evidence of the importance of diastolic ventricular interaction in certain acute and chronic disease processes, including heart failure.

Animals↗
PubMed2005

Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment.

BACKGROUND: Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires a novel approach to therapy. Perhexiline is an antianginal drug that augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects of perhexiline treatment in CHF patients. METHODS AND RESULTS: In a double-blind fashion, we randomly assigned patients with optimally medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (VO2max), an important prognostic marker. In addition, the effect of perhexiline on myocardial function and quality of life was assessed. Quantitative stress echocardiography with tissue Doppler measurements was used to assess regional myocardial function in patients with ischemic CHF. 31P magnetic resonance spectroscopy was used to assess the effect of perhexiline on skeletal muscle energetics in patients with nonischemic CHF. Treatment with perhexiline led to significant improvements in VO2max (16.1+/-0.6 to 18.8+/-1.1 mL . kg(-1) . min(-1); P<0.001), quality of life (Minnesota score reduction from 45+/-5 to 34+/-5; P=0.04), and left ventricular ejection fraction (24+/-1% to 34+/-2%; P<0.001). Perhexiline treatment also increased resting and peak dobutamine stress regional myocardial function (by 15% and 24%, respectively) and normalized skeletal muscle phosphocreatine recovery after exercise. There were no adverse effects during the treatment period. CONCLUSIONS: In patients with CHF, metabolic modulation with perhexiline improved VO2max, left ventricular ejection fraction, symptoms, resting and peak stress myocardial function, and skeletal muscle energetics. Perhexiline may therefore represent a novel treatment for CHF with a good safety profile, provided that the dosage is adjusted according to plasma levels.

Aged↗
PubMed2005

Reversal of inappropriate peripheral vascular responses in hypertrophic cardiomyopathy.

OBJECTIVES: We assessed the frequency of abnormal forearm vasodilator responses during lower body negative pressure (LBNP) in 21 non-obstructive hypertrophic cardiomyopathy (HCM) patients (31 +/- 8 [20 to 43] years) with abnormal blood pressure response (ABPR) to exercise and the effects of three drugs used to treat vasovagal syncope (propranolol, clonidine, and paroxetine) in a double-blind crossover study. BACKGROUND: Some HCM patients have an ABPR to exercise, which may be due to paradoxical peripheral vasodilatation. A similar proportion has paradoxical forearm vasodilatation during central volume unloading using LBNP. These abnormal reflexes may be caused by left ventricular mechanoreceptor activation. Similar mechanisms may also contribute to some cases of vasovagal syncope. METHODS: Blood pressure changes were assessed during exercise, and forearm vascular responses and baroreceptor sensitivity were assessed during LBNP using plethysmography. RESULTS: Nine (43%) patients (group A) had paradoxical vasodilator responses (forearm vascular resistance [FVR] fell by 7.5 +/- 4.6 U), and 12 (57%) patients (group B) had normal vasoconstrictor responses during LBNP (FVR increased by 7.7 +/- 4.9 U). Paroxetine augmented systolic blood pressure (SBP) during exercise in group A (21 +/- 6 mm Hg vs. 14 +/- 11 mm Hg at baseline, p = 0.02); no effect was detected in group B. Paroxetine reversed paradoxical vascular responses during LBNP in seven (78%) patients from group A. Propranolol and clonidine had no significant effect on SBP during exercise but reversed paradoxical vascular responses in some patients from group A (n = 5 and n = 3). CONCLUSIONS: Paradoxical vasodilatation during LBNP occurs in 40% of patients with ABPR during exercise and is reversed by propranolol, clonidine, and paroxetine. Paroxetine also improved SBP response to exercise.

Adrenergic beta-Antagonists↗
PubMed2003

Evaluation of the effectiveness of two clinical training procedures to elicit yes/no responses from patients with a severe acquired brain injury: a randomized single-subject design.

PRIMARY OBJECTIVE: Thirteen (10 males) participants with severe acquired brain injuries (ABI) were randomly assigned to two treatments, A or B (ABAB, BABA) in a crossover study to determine which treatment approach elicited more consistent and reliable yes/no responses. RESEARCH DESIGN: Treatment A consisted of an enriched stimulus environment, collaborative multidisciplinary interventions and additional yes/no response training, while Treatment B consisted of the standard hospital environment and interventions. MAIN OUTCOMES: An ANOVA showed no order effect (AB vs BA; p=0.60), but a trend (A vs B;p=0.07) towards statistical significance for increased responsiveness with treatment A. Inter-raterreliability (n=10) ranged from fair-to-good, intra class correlation (ICC) 0.51; 95% confidence interval (CI) (0.29-0.93). Post-hoc analyses showed statistically significant increased responsiveness for four participants with treatment A (p<0.001). CONCLUSION: Evidence is provided that enhanced communication strategies can improve responsiveness in a sub-group of participants with severe acquired brain injuries.

Adolescent↗
PubMedDate not supplied

Ventricular-arterial and ventricular-ventricular interactions and their relevance to diastolic filling.

Chronic heart failure is a common clinical problem, and, until recently, attention has focused predominantly on those patients with reduced left ventricular (LV) systolic function, as evidenced by a reduced LV ejection fraction. However, nearly half of all patients thought clinically to have heart failure have a "preserved" LV ejection fraction, variously defined as greater than 40% to 45% ("heart failure with normal ejection fraction" syndrome). The interaction of the heart with the systemic vasculature, termed ventricular-arterial coupling, is a key determinant of cardiovascular performance. The capacity of the body to augment cardiac output, regulate systemic blood pressure, and respond appropriately to elevations in heart rate and preload depends on both the properties of the heart and the properties of the vasculature into which the heart ejects blood. Although the marked increase of arterial and cardiac stiffness with aging can maintain ventricular-vascular coupling within a normal range, it does have detrimental effects on hemodynamic stability and cardiac reserve. Patients with heart failure with normal ejection fraction have been shown to have both arterial and ventricular stiffening, resulting in enhanced pressure-load dependence and sensitivity of blood pressure to circulating volume and diuretics. There is also indirect evidence to suggest that on exercise, increased external constraint to LV filling (as a result of diastolic ventricular interaction and pericardial constraint) may contribute to impaired use of the Starling mechanism in this group of patients.

Arteries↗
PubMedDate not supplied

Profiles of inflammatory cytokines following colorectal surgery: relationship with wound healing and outcome.

Inflammation is an essential component of normal wound healing. This study has correlated systemic (plasma) and local (wound fluid) concentrations of inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-alpha [TNF-alpha], and IL-1beta) with wound healing and surgical outcome following elective colorectal surgery. Paired plasma and wound fluid samples were collected (n = 44) postoperatively (days 1, 3, 5, 7) and analyzed by enzyme-linked immunosorbent assay (pg/mL). Cytokine levels were significantly greater in drain fluid than plasma on each postoperative day (POD); e.g., POD 1 : IL-6; drain fluid, median, 77,050 pg/mL (range 9,928-456,408); plasma, 241 pg/mL (22-1,333). Daily profiles of IL-6 and TNF-alpha were similar in drain fluid and plasma; IL-6 levels peaked on POD 1 decreasing to POD 7, and TNF-alpha levels increased from PODs 1 to 7. However, IL-1beta in plasma peaked on POD 1 and plateaued, whereas drain fluid showed two peaks (PODs 1 and 7). Only plasma levels of cytokines correlated to clinical parameters; IL-6 levels significantly correlated with postoperative complications; e.g., POD 5, complications 92(1-597) and no complications, 14(2-217). IL-6 also correlated with tumor pathology (Dukes stage, tumor depth, vascular invasion), and TNF-alpha levels correlated with the estimated blood loss during surgery. We conclude that local wound levels of cytokines correlated with the stage of wound healing, whereas systemic levels correlated with postoperative complications and tumor pathology.

Adult↗