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Biomedical subjects

M A Weber

Publications and source records attributed to M A Weber.

At least 55 records · Page 3Linked to original sources
PubMed1999

[30-day mortality after heart surgery: a pilot project of the Working Party of Directors of Hospital Cardiology Departments].

BACKGROUND AND OBJECTIVE: 30-day mortality after operation is generally accepted as a central standard of quality, especially in regard to cardiac operations. The Working Party of Directors of Hospital Cardiology Departments (Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte, ALKK) in Germany set up a pilot project to analyse whether by direct communication with patients by a database centre the expenditure incurred in collecting complete data can be decisively reduced and full documentation of outcome can in this way be obtained even for a large multi-centre patient cohort. PATIENTS AND METHODS: Between 1.6.1997 and 31.3.1998, data were consecutively collected by questionnaire on all patients registered for a cardiac operation at 85 of the 135 ALKK centres. The questionnaire included data about each patient and the indication for operation as well as the estimate of operative risk, assigned to one of five risk categories by the referring cardiologist either alone or in conjunction with the cardiac surgeon. RESULTS: Until 30.9.1998, the data were obtained on 11,349 patients who had given informed consent (response rate 99.99%), including survival figures. 824 (7.3%) patients had not undergone the planned cardiac surgery, 134 having died before the data of operation. The 30-day postoperative mortality, obtained in 99.99% of the 10,525 patients, was 3.92%. The operative mortality was lowest, at 3.73%, for aortocoronary bypass only (n = 7932), highest for aortocoronary bypass plus valvular operation (n = 785), at 8.04%. There was good agreement between the cardiologists' preoperative risk assessment and the observed mortality. CONCLUSIONS: The 30-day mortality after cardiac operation can be obtained almost completely and with reasonable expenditure even for a large patient cohort. The results confirm that hospital mortality data definitely understate the overall operative risk. The methodology used in this pilot project, namely the inclusion of information from the patients by questionnaire, can also be applied to clinical results in other areas.

Adult↗
PubMed1999

Dynamics of single dye molecules observed by confocal imaging and spectroscopy.

The fluorescence emission of single rhodamine dye molecules (rhodamine 6G and rhodamine 630) at room temperature was analyzed by using scanning confocal laser microscopy in conjunction with polarization analysis, fluorescence spectroscopy, time-resolved detection (minutes to microseconds), and excitation saturation. Results are presented and discussed 1) for samples with dye molecules at the glass-air interface and 2) covered with an additional thin protective polymer film (polyvinylbutyral). Under the polymer layer, the single-molecule fluorescence was more stable than the glass-air interface. This result may be explained by fewer spontaneous variations of the fluorescence rate, polarization changes, spectral shifts, and longer photochemical lifetimes.

Fluorescent Dyes↗
PubMed1999

Comparisons of the effects of different long-acting delivery systems on the pharmacokinetics and pharmacodynamics of diltiazem.

The benzothiazepine calcium channel antagonist diltiazem is a short-acting drug. To achieve effective 24-h blood pressure control with once-daily dosing, it relies on various extended drug-delivery systems that have grown in importance as a result of the recent reports relating the use of short-acting calcium channel antagonists to increased cardiovascular morbidity. This study examines the pharmacokinetics and resulting pharmacodynamics of two different delivery systems, each loaded with 240 mg of diltiazem and administered to 40 moderately hypertensive patients in a randomized, double-blind crossover trial. After a 4-week, single-blind placebo lead-in, patients with a clinical diastolic blood pressure of > or =100 mm Hg were randomized to either the single or dual microbead diltiazem delivery system for a 4-week period. At the end of this period, each subject was evaluated with 24-h ambulatory blood pressure monitoring and subjected to 24-h inpatient pharmacokinetic analysis on separate days. This was followed by a similar 4-week period in which each subject was treated with the alternative delivery system. For diltiazem, the area under the curve for plasma concentration versus time and the maximum plasma concentration attained by the single microbead system exceeded the values achieved by the dual bead system by 15% and 25%, respectively. These differences were greatest from the 3rd through the 13th h after dosing. During this period, both systolic and diastolic ambulatory blood pressure was significantly lower when the single microbead system was used. When compared with baseline blood pressure, blood pressure reductions achieved with the single microbead system exceeded reductions achieved with the dual microbead system by at least 2 mm Hg for 10 of the 24 postdose hours. Heart rates were slightly reduced but not significantly different. This improved blood pressure control at higher plasma levels of diltiazem suggests that a more efficient delivery system could provide better blood pressure control for identical doses of diltiazem.

Adult↗
PubMed1999

Interrupting the renin-angiotensin system: the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of hypertension.

The renin-angiotensin system has two roles in clinical hypertension: its vasoconstrictor properties directly govern blood pressure, and its actions on arterial smooth muscle, connective tissue, and endothelial integrity affect cardiovascular prognosis. Additionally, the direct actions of angiotensin II on the function and structure of the heart and renal vasculature influence clinical events. Angiotensin-converting enzyme (ACE) inhibitors have produced functional and clinical outcome benefits in clinical trials of patients with congestive heart failure, systolic dysfunction after myocardial infarction, and diabetic nephropathy. Similar favorable trends have been noted in observational studies in hypertension. Because such enzymes as chymase can substitute for ACE, the ACE inhibitors may not completely block angiotensin II formation, although they enhance bradykinin accumulation and secondarily stimulate nitric oxide and vasodilatory prostaglandins. Angiotensin II receptor blockers (ARB) selectively block the angiotensin II type 1 (AT1) receptor that not only mediates the known effects of angiotensin II but, according to recent reports, might be responsible for sequestering angiotensin II molecules in renal and cardiac cells. Moreover, by increasing plasma concentrations of angiotensin II, the ARB stimulate the unblocked angiotensin II type 2 (AT2) receptors, which-if they exist in meaningful numbers in human hypertension-mediate additional vasodilatory and antiproliferative effects. The contrasting actions of these two classes of drugs might be clinically relevant. For example, they may have additive antihypertensive efficacy; they have differing effects on renal plasma flow; and in a small pilot study of patients with congestive heart failure, the ARB demonstrated an apparent advantage in survival. Ongoing clinical trials will try to determine whether the effects of ARB can equal or even exceed the beneficial effects of ACE inhibitors on cardiovascular prognosis.

Angiotensin Receptor Antagonists↗
PubMed1999

Is high blood pressure a late manifestation of the hypertension syndrome?

Because hypertension has generally been defined as a disease of elevated systolic and diastolic blood pressure, the goals of treating hypertension have been simply to normalize the blood pressure. It was believed that if normal blood pressure were achieved, patients with hypertension would experience significant reductions in the incidence of associated cardiovascular events. However, studies to assess cardiovascular events in patients with hypertension have repeatedly demonstrated that reducing blood pressure results in very impressive reductions in cerebrovascular disease but in reductions of only about 16% in coronary artery disease, which is far lower than what was statistically predicted from the reductions in blood pressure. Although there are probably several reasons for the poor rate of reductions in the incidence of coronary artery disease, one of the most compelling appears to be the realization that hypertension is not simply a disease of numbers but rather a complex inherited syndrome of cardiovascular risk factors, all of which contribute to the development of heart disease in these patients. Included in the hypertension syndrome are abnormalities of lipid profile and insulin resistance, changes in renal function, endocrine changes, obesity, abnormalities of coagulation factors, and changes in the structure and function of the left ventricle and of vascular smooth muscle in the vasculature. In many patients, high blood pressure is a late manifestation of this disease process and is preceded by some or all of the associated cardiovascular risk factors. This paradigm suggests that therapeutic strategies for hypertension should be interventions that target both the hemodynamic and nonhemodynamic mechanisms of this syndrome to more completely reduce cardiovascular morbidity and mortality in patients with hypertension.

Antihypertensive Agents↗
PubMed1999

The ethics of using placebo in hypertension clinical trials.

USE OF PLACEBO CONTROLS: Placebo controls can enhance the value of two types of hypertension trials: measurement of the blood pressure-lowering efficacy of antihypertensive treatment and determination of whether therapeutic interventions can affect clinical endpoints. However, the possibility of adverse outcomes in hypertensive patients allocated to placebo therapy raises ethical concerns. EFFICACY STUDIES: Placebo controls in efficacy studies are particularly helpful in thoroughly quantifying the effect of treatment. The hazard to patients can be minimized by exposing them to placebo for the least possible amount of time and, assuming that blood pressure is itself the primary variable, reducing the probability of cardiovascular events by excluding subjects with severe hypertension or major concomitant risk factors. ENDPOINT STUDIES: Endpoint studies present a more difficult challenge, for they are designed in anticipation of cardiovascular events and patients at high risk are often enrolled in order to more rapidly achieve the required number of endpoints for statistical analysis. In such circumstances, positive therapeutic controls, despite the complexities of analysis, must be preferred to placebo. EARLY-STAGE HYPERTENSION: Important questions regarding the management of early-stage hypertension remain, and despite official treatment guidelines recommendations, currently based chiefly on extrapolation and judgement, many physicians routinely withhold therapy in mild hypertension, even when other risk factors are present. With appropriate safeguards, placebo-controlled trials may be necessary to examine potential benefits of therapy in such patients. Indeed, resolving therapeutic uncertainty and creating well founded recommendations for the future management of the many patients with milder forms of hypertension can make placebo controls both ethical and appropriate.

Blood Pressure↗
PubMed1999

What are the approaches for evaluating antihypertensive treatment by 24 h ambulatory blood pressure monitoring?

Measurements of trough blood pressure in a clinic setting have been the traditional method of assessing the efficacy of antihypertensive agents. The duration of action of antihypertensive drugs has been assessed by calculation of a trough-to-peak ratio; drugs with a trough-to-peak ratio greater than 50% are typically given once-a-day indications. However, the use of clinical measurements to assess antihypertensive agents can be misleading. Ambulatory blood pressure monitoring is a simple technique that provides accurate and reproducible data on both the efficacy and duration of action of antihypertensive agents. Although several complicated techniques have been used for the analysis of ambulatory blood pressure data, studies have demonstrated that calculation of simple blood pressure means (24 h mean, day-time mean and night-time mean) will provide all the data required to assess the efficacy of a drug. Calculations of systolic and diastolic load also provide useful information, and the index correlates closely with target-organ damage. Assessing the reduction of blood pressure during the last 2-6 h of the dosing interval provides critical information on the duration of action of agents with once-a-day dosing. Trough-to-peak ratio can also be calculated from an ambulatory blood pressure monitor. Furthermore, a simple line graph constructed from hourly means makes available, at a simple glance, a large amount of information about a drug. The reproducibility of ambulatory monitoring, together with the absence of placebo effect and the ability to exclude patients with white-coat hypertension, make the technique an extremely powerful tool for the assessment of antihypertensive agents that clearly provides more data on the efficacy and duration of action of an antihypertensive agent than do traditional clinical measurements.

Antihypertensive Agents↗
PubMed1998

Comparison between moexipril and atenolol in obese postmenopausal women with hypertension.

The present study investigated the effect of the new ACE-inhibitor moexipril versus the beta 1-adrenergic blocker atenolol on metabolic parameters, adverse events (AEs) and sitting systolic (SSBP) and sitting diastolic blood pressure (SDBP) in obese postmenopausal women with hypertension (stage I and II). After a 4-week placebo run-in phase, 116 obese, postmenopausal women with primary hypertension were randomised into two treatment groups receiving once daily dosages of either moexipril 7.5 mg or atenolol 25 mg initially (mean age: 57 +/- 7 years in both groups; mean weight: 94 kg in the moexipril group and 89 kg in the atenolol group, corresponding to a body mass index (BMI) of 35.2 kg/m2 and 34.1 kg/m2 in both groups, respectively). After 4 and 8 weeks, the dosages were uptitrated to moexipril 15 mg, or if necessary to moexipril 15 mg/hydrochlorothiazide (HCTZ) 25 mg, or to atenolol 50 mg and atenolol 50 mg/HCTZ 25 mg, in patients whose blood pressure was not sufficiently controlled. At endpoint, metabolic parameters (total cholesterol, triglycerides, LDL, HDL, glucose, insulin) were not significantly altered in either treatment group. Most frequent adverse events under monotherapy (moexipril/atenolol) were asthenia (5.3/13.0%), headache (13.2/21.7%), cough (7.9/6.5%), pharyngitis (21.1/8.7%) and peripheral oedema (5.3/13.0%). Overall at least one AE was reported in 66% of the patients treated with moexipril and in 78% of those treated with atenolol. Reduction of SSBP/SDBP at endpoint was 14.7 +/- 1.9/10.0 +/- 1.1 and 8.7 +/- 1.9/8.4 +/- 1.1 mmHg after treatment with moexipril and atenolol, respectively. The results showed that moexipril and atenolol are equally effective in reducing blood pressure without adversely affecting blood lipids and carbohydrate metabolism.

Adrenergic beta-Antagonists↗
PubMed1998

Comparative accuracy of three automated techniques in the noninvasive estimation of central blood pressure in men.

Automated devices have regularly replaced manual sphygmomanometry for the determination of blood pressure not only in homes and clinics, but also in emergency and critical care settings. Few studies exist that correctly assess the accuracy of these devices, and even fewer that specifically compare commercially available units that rely on different physiologic events for measurement. Six hundred pressure measurements were obtained from 120 subjects using 1 of 3 randomly selected blood pressure monitors. In addition, central arterial pressure measurements were obtained simultaneously and directly from the ascending aorta of each subject. Overall, these devices tended to overestimate diastolic (+2.5 mm Hg, p < 0.0001) and mean (+3.8 mm Hg, p < 0.0001) pressures, but not systolic (+0.7 mm Hg, p = NS) pressure. Compared with the other 2 devices, device I, relying on oscillometric detection, demonstrated a significantly smaller mean absolute error for diastolic pressure (4.9 +/- 3.0 vs 7.0 +/- 4.8 and 6.2 +/- 5.3 mm Hg, p < 0.0001) and mean pressure (4.0 +/- 3.2 vs 7.8 +/- 5.9 and 8.6 +/- 7.5 mm Hg, p < 0.0001), and a trend toward smaller error with systolic pressure (6.8 +/- 6.5 vs 7.3 +/- 6.8 and 8.0 +/-5.6 mm Hg, p = 0.19). Clinically significant (+/-10 mm Hg) errors were common with each device (24.8% overall), but serious (+/-20 mm Hg) errors were unusual (3.2%) and did not occur at all with device I during diastolic and mean pressure measurement. All of the devices tested could be expected to perform satisfactorily in most clinical settings provided that an average error of 4.0 to 8.6 mm Hg is tolerable. This level of accuracy typically extended throughout the range of pressures anticipated in most noncritical clinical situations. As implemented in the devices tested, noninvasive measurement by oscillometry with stepped deflation is more accurate than automated auscultation.

Adult↗
PubMed1998

Comparison of effects of controlled onset extended release verapamil at bedtime and nifedipine gastrointestinal therapeutic system on arising on early morning blood pressure, heart rate, and the heart rate-blood pressure product.

We assessed the differential effects of a chronotherapeutic agent (controlled-onset extended release [COER] verapamil), administered at bedtime versus a conventional, homeostatic therapy (nifedipine gastrointestinal therapeutic system [GITS]) taken in the morning, on early morning and 24-hour blood pressure (BP), heart rate (HR), and the HR x systolic BP product. The study was a multicenter (n = 51), randomized, double-blind prospective clinical trial with a 10-week treatment period. Dose titration was performed by study investigators based on systolic and diastolic BP values at the doctor's office. Ambulatory BP monitoring was performed at placebo baseline, after 4 weeks of stable double-blind therapy, and at end of the study. Twenty-four-hour BP profiles were studied in 557 hypertensive patients. Changes in BP, HR, slope of the rate of rise of BP and HR, and the HR-systolic BP product during the 4 hours from 1 hour before to 3 hours after awakening were evaluated. The study was powered to show equivalence between the 2 regimens, predefined as a difference between treatment groups in mean change from baseline in early morning BP of +/- 5 mm Hg systolic and +/- 3 mm Hg diastolic. Changes in the early morning BP fell within the definition of equivalence for the 2 treatment strategies (-12.0/-8.2 mm Hg for COER-verapamil and -13.9/-7.3 mm Hg for nifedipine GITS). Changes in both the early morning HR and rate-pressure product were significantly greater following COER-verapamil therapy versus nifedipine GITS (HR, -3.8 beats/minute vs +2.6 beats/minute, p < 0.001 and HR-systolic BP product, -1,437 beats/min x mm Hg vs -703 beats/min x mm Hg, respectively, p < 0.001). Changes in ambulatory BP demonstrated clinically similar reductions for the awake period, but nifedipine GITS lowered systolic BP to a greater extent than COER-verapamil during sleep (-11.0 vs -5.8 mm Hg, p < 0.001). COER-verapamil and nifedipine GITS had equivalent effects (+/- 5/3 mm Hg) on early morning BP. In addition, both extended-release calcium antagonists effectively lowered 24-hour BP. However, COER-verapamil had greater effects than nifedipine GITS on early morning hemodynamics (HR, HR-systolic BP product, rate of rise of BP and HR) and lesser effects during sleep due to its intrinsic pharmacologic properties and chronotherapeutic delivery system.

Analysis of Variance↗
PubMed1998

Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial.

The Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial is a randomized, prospective, double-blind, parallel-group, two-arm, actively controlled, multicenter, international 5-year clinical trial involving 15,000 patients. CONVINCE will compare the incidence of fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, or cardiovascular-disease-related death in two antihypertensive treatment regimens. One treatment arm begins with controlled onset-extended release (COER)-verapamil, which has its major antihypertensive effect 6-12 hours after administration. The other arm (standard of care (SOC)) begins with either hydrochlorothiazide (HCTZ) or atenolol, one of which is preselected by the investigator for an individual patient prior to randomization. Secondary objectives include comparisons of the regimens for each of the components of the primary endpoint (separately), death or hospitalization related to cardiovascular disease, efficacy in lowering blood pressure to goal, primary events occurring between 6 am and noon, all-cause mortality, withdrawals from blinded therapy, cancer, and hospitalizations due to bleeding. Patients may be enrolled if they are hypertensive and at least 55 years of age and have an established second risk factor for cardiovascular disease. Initial medications include COER-verapamil (180 mg/d), HCTZ (12.5 mg/d), or atenolol (50 mg/d). Initial doses are doubled if blood pressure (BP) does not reach goal (systolic BP < 140 mm and diastolic BP < 90 mm Hg). If BP is not controlled by the higher dose of the initial medication, HCTZ is added to COER-verapamil, or the SOC choice not initially selected is added in the SOC arm. An ACE-inhibitor is recommended (although nearly any open-label medication is allowed) as the third step for patients whose BP is not adequately controlled or who have a contraindication to one of the two SOC medications. Patients take two sets of tablets daily, one in the morning and one in the evening. Although most patients switch from an established antihypertensive medication to randomized treatment, untreated patients with stages I-III hypertension (SBP between 140 and 190 or DBP between 90 and 110 mm Hg) are eligible. Outcomes are monitored by an independent Data and Safety Monitoring Board. Enrollment began during the third quarter of 1996, and follow-up is to be completed in the third quarter of 2002.

Aged↗
PubMed1998

Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension.

Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses > or = 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.

Aged↗
PubMed1998

Translating data on antihypertensive drugs into clinical practice.

Two problems in the treatment of hypertension continue to be largely unsolved. The first, and more simple, is our inability to adequately control blood pressure in the majority of hypertensive patients. This not only reflects the difficulty of retaining patients in effective treatment programs, but also of convincing physicians to strive for optimal blood pressure levels. There is a continuing need for new antihypertensive drugs and combinations to help accomplish these goals. The second major problem is that the major clinical endpoints, including coronary events and renal failure, have not been adequately reduced by traditional therapies. Standard regimens, particularly those including diuretics, have protected against strokes and heart failure. Our improved understanding of vascular biology in hypertension has directed interest to the mechanisms in hypertensive patients that might accelerate atherosclerosis and vascular events in these individuals. This involves addressing the concomitant metabolic risk factors that comprise the "Hypertension Syndrome," and, perhaps of equal importance, finding therapies that directly inhibit unwanted types of growth and proliferative activities within the walls of critical arteries. Many substances within the endothelium and the vascular wall may participate as initiators or mediators of pathology, but most information thus far has focused on the renin-angiotensin system. Angiotensin converting enzyme inhibitors (and potentially angiotensin receptor blockers) have provided coronary and renal protection in various cardiovascular conditions, though not yet in formal hypertension trials. Calcium channel blockers have also shown promise, including recent stroke and cardiovascular benefits in patients with isolated systolic hypertension, but, again, definitive coronary data in hypertension are awaited. Unless concomitant conditions mandate the selection of a particular antihypertensive drug class, physicians currently have a dilemma: should they choose drugs from older classes that have not provided full protection? Or, should they prescribe newer agents with exciting potential but with, as yet, unproved endpoint benefits in hypertension? Until currently ongoing prospective trials of antihypertensive therapy are completed, physicians must be guided by their own interpretations of the available data.

Antihypertensive Agents↗
PubMed1998

Unsolved problems in treating hypertension: rationale for new approaches.

Two major problems continue to challenge hypertension experts and clinical practitioners. The first is the apparently simple issue of controlling blood pressure; only one-quarter of hypertensive patients in the United States have blood pressures reduced to less than 140/90 mm Hg. Even those known to be receiving treatment have barely a 50% success rate. Explanations include inadequate commitments by physicians to achieve target blood pressures, but it is also likely that effectively decreasing blood pressure--despite the currently available panoply of antihypertensive agents--is a truly difficult task. The second problem is that despite our success in decreasing stroke incidence, hypertension treatment with traditional agents, largely diuretic-based, has not adequately protected patients against coronary events and renal insufficiency. Such new drug classes as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and calcium channel blockers exhibit vascular effects that might inhibit atherosclerotic changes and reduce clinical events, but we are still awaiting definitive confirmation of these properties from ongoing clinical outcomes studies in hypertension. Therapy with fixed combinations of antihypertensive drugs is now recognized as a potentially useful approach. Innovative combinations, including ACE inhibitors and calcium channel blockers, can provide enhanced antihypertensive efficacy while avoiding or minimizing adverse metabolic and clinical side effects. These approaches are also convenient and cost-effective. It remains to be learned whether newer drug combinations might exhibit additive cardiovascular protective actions.

Angiotensin-Converting Enzyme Inhibitors↗