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Biomedical subjects

P Carson

Publications and source records attributed to P Carson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Mild systolic dysfunction in heart failure (left ventricular ejection fraction >35%): baseline characteristics, prognosis and response to therapy in the Vasodilator in Heart Failure Trials (V-HeFT)

OBJECTIVES: This analysis sought to evaluate the clinical characteristics and outcome in heart failure with mild systolic dysfunction. BACKGROUND: Although heart failure with mild systolic dysfunction occurs commonly, this is an understudied area because clinical trials have usually excluded patients with ejection fraction >35%. METHODS: The 422 patients with left ventricular ejection fraction </=35% were compared with 172 with a left ventricular ejection fraction >35% in the Vasodilator in Heart Failure Trial (V-HeFT I), whereas in V-HeFT-II 554 patients with a left ventricular ejection fraction </=35% were compared with 218 patients with a left ventricular ejection fraction >35% for mortality and clinical care. For a left ventricular ejection fraction >35%, treatment with hydralazine/isosorbide dinitrate was compared with prazosin and placebo therapy in V-HeFT I, and hydralazine/isosorbide dinitrate was compared with enalapril in V-HeFT II for mortality, clinical course and change in physiologic variables: ejection fraction, plasma norepinephrine levels, ventricular tachycardia and echocardiographic variables. RESULTS: In both studies, patients with a left ventricular ejection fraction >35% differed principally in hypertensive history, higher functional capacity and radiographic and echocardiographic cardiac dimension from patients with a left ventricular ejection fraction </=35%, and plasma norepinephrine levels differed in V-HeFT II (p < 0.01). Patients with a left ventricular ejection fraction >35% had a lower cumulative mortality than those with a left ventricular ejection fraction </=35% (p < 0.0001) and less frequent hospital admissions for heart failure (p < 0.014, V-HeFT I; p < 0.005, V-HeFT II). Although cumulative mortality and morbidity did not differ between treatment groups in V-HeFT I, enalapril decreased overall mortality versus hydralazine/isosorbide dinitrate (p < 0.035) in V-HeFT II. For physiologic variables in V-HeFT II, enalapril decreased ventricular tachycardia at follow-up (p < 0.05). CONCLUSIONS: In V-HeFT, heart failure with mild systolic dysfunction was associated with different characteristics and a more favorable prognosis than heart failure with more severe systolic dysfunction. Enalapril decreased overall mortality and sudden death compared with hydralazine/isosorbide dinitrate. Prospective trials are needed to address therapy for heart failure with mild systolic dysfunction.

Aged↗
PubMed1996

Pharmacologic treatment of congestive heart failure.

Congestive heart failure is a clinical syndrome producing symptomatic deterioration, functional impairment, and shortened life span. The syndrome is complex in that it includes both peripheral and cardiac effects which contribute to the progression of heart failure. In the periphery, elevations in the sympathetic nervous system and renin-angiotensin system increase afterload and contribute to further salt and water retention. The central cardiac abnormalities include remodeling of the heart and downregulation of beta receptors. Traditional heart failure therapy has included treatment of fluid retention with diuretics, although their effect on mortality has never been addressed. The most proven therapy in heart failure is treatment with vasodilators, particularly angiotensin-converting enzyme (ACE) inhibitors. Improved survival with ACE-inhibitor therapy has been demonstrated in patients with severe heart failure (CONSENSUS), mild to moderate heart failure (SOLVD), and in comparison with vasodilator therapy with hydralazine isosorbide dinitrate (VHeFT II). Improved survival has also been noted in postmyocardial infarction when the ejection fraction is decreased (SAVE). The ACE inhibitors have now become standard therapy for heart failure regardless of severity. Additive vasodilator therapy with calcium-channel antagonists is under investigation. Inotropic therapy is controversial at present because of disappointing mortality results. The clinical mainstay digitalis remains without convincing mortality reduction data. Other inotropic agents, particularly phosphodiesterase inhibitors, have shown uniformly negative survival results. However, the new mixed action agents vesnarinone and pimobenden have shown favorable data, with vesnarinone demonstrating a mortality reduction effect. Beta-blocker therapy in heart failure has also found renewed interest, particularly with the new agents carvedolol and bucindolol which also have vasodilating properties.

Drug Therapy, Combination↗
PubMed1996

Topically applied recombinant tissue plasminogen activator for the treatment of venous ulcers. Preliminary report.

BACKGROUND: Increasing evidence suggests that fibrin deposition is an important pathogenic component of venous ulceration and that fibrin removal could accelerate ulcer healing. OBJECTIVE: We sought to determine whether topical application of recombinant tissue plasminogen activator (tPA) compounded in 1% hyaluronate acid (HA) can be used safely in venous ulcers and whether it can accelerate healing. METHODS: Twelve patients were randomized in a double-blind fashion in three sequential groups of four subjects each, so as to receive daily topical application of either placebo (HA alone, one patient) or tPA/HA (three patients) at escalating doses of 0.25, 0.5, and 1.0 mg/ml of tPA for 4 weeks. RESULTS: No safety problems occurred, and we found a close direct correlation between mean ulcer reepithelialization, fibrin removal, and the dose of topically applied tPA (r = 0.991). CONCLUSION: In this first study to examine its usefulness, topically applied tPA appears to be a safe and promising agent for treating venous ulcers.

Administration, Cutaneous↗
PubMed1993

Investing in the comeback: parent's experience following traumatic brain injury.

The increasing incidence of survival following traumatic brain injury necessitates a closer examination of long-term care and caregiver issues. A sample of parents and brain-injured offspring from 20 families was explored to identify a qualitatively-generated theory describing the parent's experience following a brain-injured child's return to the home setting. The grounded theory methodology was used during data collection and analysis. All the brain-injured offspring had survived moderate to severe traumatic brain injury, were living with at least one parent, and were aged 17-34 years. Investing in the Comeback is the generated three-phase theory. These three phases--centering on, fostering independence and seeking stability describe the work of parents living with brain-injured offspring.

Adolescent↗
PubMed1993

Anticardiolipin antibodies in ischaemic heart disease: marker or myth?

OBJECTIVES: To assess the incidence and significance of anticardiolipin antibodies after myocardial infarction and in unstable angina. DESIGN: A prospective study of all patients under 60 admitted to the coronary care unit over a 12 month period with a diagnosis of acute myocardial infarction who were followed up for a further 12 months. Patients admitted with unstable angina were similarly assessed but not followed up. Anticardiolipin antibody concentrations were compared with those of age matched controls. SETTING: A district general hospital. PATIENTS: 307 patients with acute myocardial infarction and 160 patients with unstable angina. RESULTS: Anticardiolipin antibody concentrations in the two patient groups did not differ significantly from those in the control groups. Antibody concentrations were not related to a history of angina or myocardial infarction nor were they related to subsequent cardiovascular complications. CONCLUSION: This study shows no significant association between anticardiolipin antibody concentrations and either myocardial infarction or unstable angina.

Angina, Unstable↗
PubMed1993

Influence of prerandomization (baseline) variables on mortality and on the reduction of mortality by enalapril. Veterans Affairs Cooperative Study on Vasodilator Therapy of Heart Failure (V-HeFT II). V-HeFT VA Cooperative Studies Group.

BACKGROUND: The effects of hydralazine plus isosorbide dinitrate were compared with those of enalapril in 804 men receiving digoxin and diuretic therapy for chronic congestive heart failure (CHF) in the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trial (V-HeFT II). METHODS AND RESULTS: Patients were randomly assigned to receive 20 mg of enalapril or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. At 2 years, treatment with enalapril resulted in a significant (28%) reduction in mortality relative to the active control treatment. Baseline variables were examined to determine their impact on risk of mortality and on relative response to treatment. Mortality rates were significantly higher in patients with severe ventricular arrhythmias; in patients with low baseline ejection fractions, low peak oxygen consumption, and low systolic blood pressures; in patients with high cardiothoracic ratios, high scores indicating greater impairment on a quality-of-life questionnaire, and high plasma norepinephrine or renin levels; and in patients in New York Heart Association (NYHA) classes III and IV. Coronary artery disease, duration of CHF, and patient age were not predictive of mortality. Enalapril reduced mortality significantly compared with hydralazine/isosorbide dinitrate in patient subgroups with high plasma renin or norepinephrine levels and in patients with low cardiothoracic ratios. Furthermore, enalapril conferred significantly greater protection from mortality than hydralazine/isosorbide dinitrate in patients in NYHA classes I and II and in patients without arrhythmias or with < or = 10 premature ventricular contractions per hour. CONCLUSIONS: Of the prerandomization characteristics that were predictive of mortality in patients with CHF, only neurohormone measurements, cardiothoracic ratios, arrhythmia severity, and NYHA class identified subgroups of patients who benefited most from treatment with enalapril; a treatment interaction across strata was detected only for plasma norepinephrine and NYHA class. In no patient subgroup was the mortality with enalapril treatment significantly higher than the mortality with hydralazine/isosorbide dinitrate treatment.

Drug Therapy, Combination↗
PubMed1993

Enalapril decreases prevalence of ventricular tachycardia in patients with chronic congestive heart failure. The V-HeFT II VA Cooperative Studies Group.

BACKGROUND: Patients with heart failure have a high prevalence of serious arrhythmias and sudden cardiac-death. METHODS AND RESULTS: Male patients aged 18-75 years with chronic heart failure were randomized to enalapril or hydralazine-isosorbide dinitrate. Short-term (4-hour to 8-hour) Holter tape recordings were performed before randomization, at 3 months, at 1 year, and yearly thereafter. Of 804 patients randomized to therapy, 715 had Holters at baseline. Couplets were noted in 56% versus 60% and ventricular tachycardia (VT) (three or more consecutive ventricular premature beats) in 27% versus 29% of patients randomized to enalapril versus hydralazine-isosorbide dinitrate, respectively. The presence of VT at 3 months, 1 year, and 2 years predicted significantly higher mortality during the subsequent year (p < 0.0001, p < 0.001, and p < 0.037, respectively). In the enalapril group, VT prevalence decreased by 27% at 1 year (p < 0.02). A decrease in prevalence of VT was not seen in the hydralazine-isosorbide dinitrate group. New VT was seen in 11% of enalapril patients versus 24% of hydralazine-isosorbide dinitrate patients at 1 year (p < 0.002). When compared with hydralazine-isosorbide dinitrate at 1 and 2 years, there was a 52% and 49% reduction, respectively, in sudden deaths in the enalapril group. Thus, at 1 and 2 years, the decrease in sudden deaths in the enalapril group coincided with the decrease in VT prevalence and the decrease in new VT emergence. CONCLUSIONS: In patients with heart failure, VT and couplets predict increased mortality. When compared with hydralazine-isosorbide dinitrate, enalapril decreases both the persistence of baseline VT at 3 months and the emergence of new VT at 1 and 2 years. The reduction in VT prevalence parallels a reduction in sudden death. The effect of enalapril on survival over hydralazine-isosorbide dinitrate may be related to its ability to reduce prevalence of ventricular arrhythmia.

Death, Sudden, Cardiac↗
PubMed1992

Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers.

A great deal of interest has been focused recently on the potential use of synthetic polypeptide growth factors to stimulate healing of chronic wounds. In this pilot double-blind randomized study conducted at a single center, we used human recombinant epidermal growth factor (h-EGF) to treat 44 patients with venous ulceration of the lower extremities. An aqueous solution (10 micrograms/mL) of h-EGF was applied topically to the ulcers twice a day until healing occurred or for a maximum of 10 weeks. Patients were evaluated weekly for measurements of ulcer size and for the formation of granulation tissue suitable for grafting. Nine patients were excluded from efficacy evaluation because of protocol violations. Therefore, 35 patients (17 h-EGF, 18 placebo) were evaluable for efficacy, and 44 patients (22 h-EGF, 22 placebo) were available for safety. The median baseline ulcer size for all patients was 18.5 cm2, and was not significantly different between h-EGF and placebo group (12.9 cm2 versus 19.2 cm2, respectively, P = .27). By study end, six (35%) of h-EGF treated patients and two (11%) in the placebo group had healed completely (P = .10). Another 6 patients (2 of 17 h-EGF, 4 of 18 placebo; P = .50) developed healthy granulation tissue that was suitable for grafting. The median ulcer size reduction was 7% for h-EGF versus 3% for placebo per week (P = .29), and 73% versus 33% at study end (P = .32). No untoward side effects were related to the application of h-EGF. We conclude that topical application of h-EGF, in the dose and manner used in this study, was safe but failed to significantly enhance re-epithelialization of venous ulcers. However, a greater reduction in ulcer size and a larger number of healed ulcers with the use of h-EGF are encouraging results.

Administration, Topical↗
PubMed1991

Congestive heart failure and converting enzyme inhibition: failure of current prognostic criteria for predicting subsequent renal insufficiency.

Angiotensin-1-converting enzyme inhibitors have an effective and established role in the treatment of patients with congestive heart failure. However, a small number of such patients will subsequently develop renal insufficiency. These patients may be identified prior to, or shortly after, commencement of therapy by recognized criteria. This report describes 4 patients with congestive heart failure who developed severe renal insufficiency secondary to either enalapril or captopril therapy in the absence of any currently recognized predisposing factors. One patient died.

Aged↗
PubMed1990

Cardiovascular and neurohormonal effects of atrial natriuretic peptide in conscious dogs with and without chronic left ventricular dysfunction.

Atrial natriuretic peptide (hANP 4-28) was infused for 1 h (0.3 microgram/kg/min) in 11 normal awake dogs and seven awake dogs with chronic left ventricular dysfunction, induced 16 weeks earlier by repetitive DC shock. The responses were similar in the two groups and included decreases in arterial pressure (107-99 mm Hg), heart rate (83-72 beats/min), and cardiac output (3.6-2.8 L/min), without changes in right or left ventricular filling pressures. Systemic vascular resistance (SVR) tended to rise during the infusion and was significantly increased (2,847-3,442 dyn s cm-5, p less than .05) during the postinfusion recovery period. Regional blood flows (microspheres) during infusion revealed a decrease in skin and splanchnic flow. Despite the apparent vasoconstrictor effect, plasma norepinephrine (PNE), renin activity (PRA), and arginine vasopressin (AVP) levels all fell during ANP infusion. These data suggest that ANP exerts a cardioinhibitory effect, possibly similar to that of arginine vasopressin (AVP), and that the net systemic vasoconstrictor effect of ANP in these dogs is mediated by a complex interrelationship between direct vascular effects, neurohormonal inhibition, and central reflex activation.

Animals↗
PubMed1989

Bacteria and gallstone nucleation.

This preliminary study reports for the first time that there might be a possible association between bacteria and the aetiology of some cholesterol calculi. The gall-bladder biles from 225 cholecystectomy patients underwent bacteriological and microscopic study. Cholesterol calculi from 13 patients (10.2%) were observed to be associated with gall-bladder bile profusely infected with at least one bacterial species that was shown to possess beta-glucuronidase activity, an enzyme that is thought to promote calcium bilirubinate precipitation in bile. Concomitantly, the associated gall-bladder bile was 'high' in calcium bilirubinate precipitation and the precipitate was also detected in the centre of the gallstones. Moreover, in approximately half of these patients (six of 13), the cholesterol gallstones' nuclear areas also contained calcium palmitate, which is also thought to be due to bacterial activity. The results also support the hypothesis that bacteria with active beta-glucuronidase (for example, Escherichia coli) can significantly influence the aetiology of brown pigment gallstones. In contrast, bacteria were observed to have no role in black pigment gallstone formation, as their associated gall-bladder biles were always observed to be sterile.

Adult↗
PubMed1988

Evaluation of a social problem-solving skills program for third- and fourth-grade students.

The effects of a social problem-solving (SPS) training program for entire classrooms of third- and fourth-grade children were examined in two studies. In the first study, experimental children showed significantly greater improvement in knowledge and performance of SPS skills than control children. However, both positive and negative effects of the intervention (varying by classroom) were found on measures of behavioral adjustment, self-efficacy, and peer acceptance at a 6-month follow-up. The second study compared two different intervention strategies: (a) SPS training with teacher-student dialoguing, peer pairing, and self-monitoring, and (b) SPS training with dialoguing only. It was found that children in both the experimental and control groups improved significantly in performance of SPS skills but no differences between the groups were found for changes in behavioral adjustment, self-efficacy, and peer acceptance. The limitations of cognitively mediated interventions for young children were discussed.

Affect↗