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Biomedical subjects

Henry Krum

Publications and source records attributed to Henry Krum.

101 records · Page 6Linked to original sources
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2002

Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients.

The efficacy and tolerability of eplerenone, a selective aldosterone blocker, was assessed when added to existing antihypertensive therapy with an ACE inhibitor or an angiotensin II receptor blocker (ARB). Hypertensive patients (n=341) whose blood pressure (BP) was not controlled despite ACE inhibitor or ARB were randomized (double-blind) to receive 50 mg eplerenone (increasing to 100 mg if required) once daily or placebo for 8 weeks. Diastolic and systolic BP and adverse events were recorded. By study end (week 8), mean seated diastolic BP was significantly reduced from week 0 among patients receiving eplerenone/ARB (-12.7+/-0.81 mm Hg) compared with those receiving placebo/ARB (-9.3+/-0.83 mm Hg). The change in mean seated diastolic BP was -9.9+/-0.88 mm Hg in eplerenone/ACE inhibitor patients and -8.0+/-0.86 mm Hg in placebo/ACE inhibitor patients (P=NS). Systolic BP levels were also significantly lower at week 8 for eplerenone/ACE inhibitor (-13.4+/-1.35 mm Hg) and eplerenone/ARB (-16.0+/-1.37 mm Hg) patients, respectively, compared with placebo/ACE inhibitor (-7.5+/-1.31 mm Hg) and placebo/ARB patients (-9.2+/-1.41 mm Hg). Adverse events were generally nonsevere and not significantly different between eplerenone and placebo. This study demonstrated that in patients whose BP was not controlled with an ACE inhibitor or ARB, the addition of eplerenone over an 8-week period significantly lowered systolic BP in both groups and diastolic BP in ARB patients. Selective aldosterone blockade with eplerenone, therefore, may be useful add-on therapy in hypertensive patients inadequately controlled on ACE inhibitor or ARB alone.

Abdominal Pain↗
PubMed2002

Altered sympathetic and parasympathetic activity in lung transplantation patients at rest and following autonomic perturbation.

STUDY OBJECTIVES: To investigate the nature and extent of the alteration in autonomic function following heterotopic lung transplantation. DESIGN: Measures of cardiac parasympathetic nervous system activity (PNSA) and systemic sympathetic nervous system activity (SNSA) were compared in lung transplant patients and age-matched healthy subjects, both at rest and following autonomic perturbation. SETTING: Lung transplantation service of a university teaching hospital. PATIENTS AND PARTICIPANTS: Twenty-two lung transplant patients (mean [+/- SEM] age, 50.5 +/- 2.4 years) and 13 healthy subjects (mean age, 48.2 +/- 3.7 years). MEASUREMENTS AND RESULTS: Lung transplant patients had decreased baseline time and frequency domain measures of heart rate variability compared to healthy subjects (root mean square of successive differences in R-R intervals, 11.2 +/- 1.1 vs 30.3 +/- 4.5 ms, respectively [p < 0.005]; LnHP, 2.4 +/- 0.2 vs 4.8 +/- 0.4 ms(2), respectively [p < 0.005]). In addition, lung transplant patients demonstrated an attenuated reduction in LnHP/LnTP following head-up tilt in comparison to healthy subjects (p < 0.05). The baseline recumbent plasma norepinephrine level was increased in lung transplant patients compared to healthy subjects (3.25 +/- 0.43 vs 2.00 +/- 0.27 nmol/L, respectively; p < 0.05), and levels increased in both groups with upright head-up tilt. There were no differences between the two groups in heart rate or mean systolic BP responses to both the Valsalva maneuver and cold pressor testing. CONCLUSIONS: Lung transplant patients have both reduced PNSA and increased SNSA at rest. Furthermore, these patients appear to have a preserved capacity to respond to autonomic perturbation by increasing SNSA. The mechanisms underlying these observations and their prognostic implications remain to be determined.

Adult↗
PubMed2002

Selective cyclo-oxygenase-2 inhibitors and myocardial infarction: how strong is the link?

There are concerns that selective cyclo-oxygenase (COX)-2 inhibitors may be prothrombotic and increase the risk of myocardial infarction. This has largely arisen because of an unexpected finding of a higher rate of myocardial infarction in patients receiving rofecoxib compared with patients receiving naproxen in a study of gastrointestinal toxicity. The results of this study, a similar study of celecoxib versus ibuprofen or diclofenac, and data obtained from a meta-analysis of aspirin (acetylsalicylic acid) primary prevention trials suggest that differences in the rates of myocardial infarction between rofecoxib and naproxen may have been due to an unexpectedly low rate of myocardial infarction in patients receiving naproxen. However, population surveillance data also suggest that rofecoxib may be associated with a greater risk of myocardial infarction than celecoxib and certain nonselective nonsteroidal anti-inflammatory drugs. The magnitude of this increase in risk, if real, is uncertain but it is likely to be relatively small in patients for whom cardiovascular prophylaxis with aspirin is not indicated. Patients who require nonsteroidal anti-inflammatory therapy for arthritis and who are at high risk of cardiovascular disease should receive aspirin, probably in conjunction with selective COX-2 inhibitor therapy, as the risk of gastrointestinal ulceration may be lower than for aspirin plus a nonselective nonsteroidal anti-inflammatory drug. In patients who do not require aspirin for the prevention of cardiovascular events, the lower risk of gastrointestinal ulceration associated with COX-2 inhibitor compared with non-selective nonsteroidal anti-inflammatory drugs would be expected to outweigh any increase in the risk of myocardial infarction, if one exists.

Celecoxib↗
PubMed2002

The role of aldosterone receptor blockade in the management of cardiovascular disease.

The recent revival of interest in aldosterone receptor antagonists for the treatment of cardiovascular disease has been underpinned by fresh insights into the pathophysiological role of aldosterone in cardiovascular disease, especially with regard to its widespread 'non-epithelial' actions, as well as by key findings from dinical studies. The therapeutic efficacy of spironolactone (Pharmacia Corp) in severe chronic heart failure is established. Emerging evidence from an extensive development program for eplerenone (Pharmacia Corp), a novel selective aldosterone receptor antagonist, may further expand the evidence base for aldosterone receptor antagonism, including its potential in treating hypertension. Importantly, eplerenone does not appear to cause the hormonal side effects observed with spironolactone.

Aldosterone↗
PubMedDate not supplied

Aldosterone antagonists: a new treatment option for patients with post-myocardial infarction heart failure.

Heart failure (HF) in association with acute myocardial infarction is an emerging clinical problem. The benefits of aldosterone blockade have now been extended, with the selective aldosterone antagonist eplerenone demonstrating reduced mortality compared to placebo, in patients with post-myocardial infarction HF. The evidence supporting this agent will be briefly reviewed, followed by a discussion on the clinical implications of aldosterone antagonists in this clinical setting.

Clinical Trials as Topic↗
PubMedDate not supplied

Reliability of isokinetic strength and aerobic power testing for patients with chronic heart failure.

PURPOSE: The objective of this study was to assess the reliability of testing skeletal muscle strength and peak aerobic power in a clinical population of patients with chronic heart failure (CHF). METHODS: Thirty-three patients with CHF (New York Heart Association (NYHA) Functional Class 2.3 +/- 0.5; left ventricular ejection fraction 27% +/- 7%; age 65 +/- 9 years; 28:5 male-female ratio) underwent two identical series of tests (T1 and T2), 1 week apart, for strength and endurance of the muscle groups responsible for knee extension/flexion and elbow extension/flexion. The patients also underwent two graded exercise tests on a bicycle ergometer to measure peak oxygen consumption (VO(2peak)). Three months later, 18 of the patients underwent a third test (T3) for each of the measures. Means were compared using MANOVA with repeated measures for strength and endurance, and ANOVA with repeated measures for VO(2peak). RESULTS: Combining data for all four movement patterns, the expression of strength increased from T1 to T2 by 12% +/- 25% (P <.001; intraclass correlation coefficient [ICC] = 0.89). Correspondingly, endurance increased by 13% +/- 23% (P =.004; ICC = 0.87). Peak oxygen consumption was not significantly different (16.2 +/- 0.8 and 16.1 +/- 0.8 mL.kg(-1).min(-1) for T1 and T2, respectively; P =.686; ICC = 0.91). There were no significant differences between T2 and T3 for strength (2% +/- 17%; P =.736; ICC = 0.92) or muscle endurance (-1% +/- 15%; P =.812; ICC = 0.96), but VO(2peak) decreased from 16.7 +/- 1.2 to 14.9 +/- 0.9 mL.kg(-1).min(-1) (-10% +/- 18%; P =.021; ICC = 0.89). CONCLUSIONS: These data suggest that in a population of patients with CHF, a familiarization trial for skeletal muscle strength testing is necessary. Although familiarization is not required for assessing oxygen consumption as a single measurement, VO(2peak) declined markedly in the 3-month period for which these patients were followed. Internal consistency within patients was high for the second and third strength trials and the first and second tests of VO(2peak).

Aged↗
PubMedDate not supplied

Recent advances in the management of chronic heart failure.

BACKGROUND: The management of chronic heart failure (CHF) has undergone a revolution in the past decade, highlighted by dramatic turnarounds in opinion, renewed focus on 'traditional' therapies and the emergence of novel diagnostic and treatment options. OBJECTIVE: Based on review of the current evidence, this article aims to provide an update of the issues pertaining to the diagnosis and treatment of CHF. DISCUSSION: Underlying this revolution on the management of CHF have been novel insights into the pathophysiology of CHF. Promising findings from recent clinical trials will also be examined in this article.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Nursing sans frontières: a three year case study of multi-state registration to support nursing practice using information technology.

OBJECTIVE: To highlight the registration issues for nurses who wish to practice nationally, particularly those practicing within the telehealth sector. DESIGN: As part of a national clinical research study, applications were made to every state and territory for mutual recognition of nursing registration and fee waiver for telenursing cross border practice for a period of three years. These processes are described using a case study approach. OUTCOME: The aim of this case study was to achieve registration in every state and territory of Australia without paying multiple fees by using mutual recognition provisions and the cross-border fee waiver policy of the nurse regulatory authorities in order to practice telenursing. RESULTS: Mutual recognition and fee waiver for cross-border practice was granted unconditionally in two states: Victoria (Vic) and Tasmania (Tas), and one territory: the Northern Territory (NT). The remainder of the Australian states and territories would only grant temporary registration for the period of the project or not at all, due to policy restrictions or nurse regulatory authority (NRA) Board decisions. As a consequence of gaining fee waiver the annual cost of registration was a maximum of dollars 145 per annum as opposed to the potential dollars 959 for initial registration and dollars 625 for annual renewal. CONCLUSIONS: Having eight individual nurses Acts and NRAs for a population of 265,000 nurses would clearly indicate a case for over regulation in this country. The structure of regulation of nursing in Australia is a barrier to the changing and evolving role of nurses in the 21st century and a significant factor when considering workforce planning.

Australia↗