Biomedical subjects

J Planellas

Publications and source records attributed to J Planellas.

13 recordsLinked to original sources

PubMed2001

Effect of hormone replacement therapy on lipids in perimenopausal and early postmenopausal women.

OBJECTIVE: To determine the effects of oral sequential hormone replacement therapy (HRT) on lipid-profile in perimenopausal and early postmenopausal women. METHODS: We performed a single-center, randomized, placebo-controlled trial. The trial was double blind with respect to 17beta-estradiol/desogestrel (17beta-E-D) and placebo and open with respect to conjugated estrogens/norgestrel (CEE-N). A total of 125 healthy perimenopausal and early postmenopausal women, aged 43-58 years, were recruited from the general population in Zoetermeer, the Netherlands. The intervention consisted of 6 months treatment with 1.5 mg 17beta-estradiol/0.15 mg desogestrel (n=53), 0.625 mg conjugated estrogens/0.15 mg norgestrel (n=36) or placebo (n=36). At baseline, cycle 1, 3 and 6, overnight fasting blood samples were obtained in which lipids were determined. We used linear regression analysis to calculate differences in mean change from baseline in lipids in the active treatment groups compared to placebo. RESULTS: In both treatment groups significant (P<0.05) falls in low-density-lipoprotein (LDL)-cholesterol (17beta-E-D: -7.8% and CEE-N: -8.4%) and lipoprotein(a) (17beta-E-D: -11.7% and CEE-N: -28.3%) were found compared to placebo. Apolipoprotein A1 (17beta-E-D: 6.8% and CEE-N: 7.3%) and HDL-cholesterol (17beta-E-D: 6.4% and CEE-N: 8.0%) significantly increased compared to placebo. No significant changes were found in the other lipids. Mean changes from baseline in total cholesterol, LDL-cholesterol and apolipoprotein B were significantly more pronounced in postmenopausal women compared to perimenopausal women, adjustment for age-differences did not change the results. CONCLUSION: Treatment of perimenopausal and early postmenopausal women with 17beta-E-D or CEE-N changes their lipid-profile in a potentially anti-atherogenic direction. Changes appear to be more pronounced in postmenopausal women compared to perimenopausal women.

Adult↗

PubMed2001

The effect of hormone replacement therapy on serum homocysteine levels in perimenopausal women: a randomized controlled trial.

Serum homocysteine levels may be lowered by hormone replacement therapy, but randomized controlled trial data are scarce. We performed a single center randomized placebo-controlled trial to assess the 6 months effect of hormone replacement therapy compared with placebo on fasting serum homocysteine levels in 121 perimenopausal women free of cardiovascular disease, and recruited from the general population. The trial was double-blind with respect to a sequential combined regimen of oral 17 beta-estradiol and desogestrel (17 beta E(2)-D) and the placebo group and open with respect to a combination of conjugated equine estrogens and norgestrel (CEE-N). At baseline and after 6 months, fasting serum homocysteine levels were measured. Differences in 6 months serum homocysteine levels from baseline between treatment and placebo groups were calculated, and expressed as a percentage of the 6 months placebo level. After 6 months, the difference in serum homocysteine levels between women receiving 17 beta E(2)-D and placebo was -6.3% (95% CI, -12.4%; 0.0%, P=0.06). The difference between women receiving CEE-N and placebo was -10.1% (95% CI, -16.7%; -2.9%, P<0.01). The difference between the combined group of both types of hormone replacement therapy users and placebo was -7.8% (95% CI, -13.2%; -2.0%, P=0.01). No significant difference was observed between the two active regimens. Our results indicate that hormone replacement therapy decreases homocysteine levels in perimenopausal women.

Adult↗

PubMed2001

Hormone replacement therapy and endothelial function. Results of a randomized controlled trial in healthy postmenopausal women.

OBJECTIVE: To compare the effects of 3 months treatment with tibolone (a single entity synthetic steroid hormone with estrogenic, progestanic and androgenic activities), or continuous combined conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA), with placebo, on endothelial function. DESIGN: A single center, randomized, double-blind, placebo-controlled study. SETTING: Research center as part of the University Medical Center Utrecht. SUBJECTS: One hundred and five healthy postmenopausal women, sampled from the general population. INTERVENTIONS: Three months treatment with tibolone or CEE+MPA or placebo. MAIN OUTCOME MEASURE: At baseline and after 3 months, endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. RESULTS: Results are presented as mean differences between treatment groups of endothelium dependent flow mediated dilatation (fmd) and endothelium independent nitroglycerine induced dilatation with 95% confidence intervals (95% CI). After treatment, there was a significant difference in mean fmd between the CEE+MPA group and the placebo group of 2.5% (95% CI: 0.3-4.6) while the tibolone group and the placebo group did not differ significantly (0.6%; 95% CI: 1.6-2.8). Nitroglycerine induced dilatation did not differ significantly between the groups. CONCLUSIONS: Hormone replacement therapy with CEE+MPA for 3 months increases endothelium dependent fmd of the brachial artery in healthy postmenopausal women. Tibolone did not alter fmd. The clinical significance of this improvement in fmd for cardiovascular disease risk needs to be established.

Aged↗

PubMed2000

A double-blind, randomized, comparative study evaluating clinical effects of two sequential estradiol-progestogen combinations containing either desogestrel or medroxyprogesterone acetate in climacteric women.

OBJECTIVES: The aim of this study was to compare a new sequential estradiol-desogestrel (E2-DSG) hormone replacement regimen (Liseta) with one of the standard treatments i.e. estradiol valerate-medroxyprogesterone acetate (E2V-MPA) combination (Klimalet) regarding the alleviation of climacteric symptoms, vaginal bleeding pattern and the occurrence of adverse experiences. METHODS: In a multicenter study performed in Denmark, a total of 376 perimenopausal women with climacteric symptoms were randomly allocated to oral sequential treatment with either E2-DSG (1.5 mg E2 for 24 days with 0.15 mg DSG for the last 12 days followed by a placebo tablet for 4 days) (n = 186) or with E2V-MPA (2 mg E2V for 21 days with 10 mg MPA for the last 10 days) (n = 190). Treatments were administered, using a double-blind, double-dummy technique for 6 cycles of 28 days. RESULTS: Three hundred and seventeen women, 158 in the E2-DSG and 159 in the E2V-MPA group, completed six treatment cycles. Both treatments reduced menopausal symptoms rapidly and to a similar extent. Hot flushes were present in 88% of the women in both groups. After six treatment cycles, hot flushes were no longer present in 71 and 62% of the women in the E2-DSG and E2V-MPA group, respectively. Perspiration decreased from 80 to 65% in the E2-DSG group and from 82 to 63% in the E2V-MPA group. Mood disturbances were present in 82% of the women in the E2-DSG at baseline, and in 52% after six cycles. In the E2V-MPA group the corresponding figures were 68 and 42%, respectively. The bleeding pattern was comparable in both treatment groups. Regular withdrawal (expected) bleeding appeared in 90-92% and in 85-90% of the women in cycles 1-5 with E2-DSG and E2V-MPA, respectively. Irregular bleeding (including spotting) occurred in 15.2% of the women receiving E2-DSG and in 20.1% of the women treated with E2V-MPA in cycle 6. In both treatment groups there was a tendency of a slight decrease in blood pressure. Adverse events were in less than 10% in each group the reason to discontinue treatment. CONCLUSIONS: Both treatments effectively alleviated menopausal complaints and presented good cycle control. Bleeding pattern and mood disturbances appeared to be more favorable influenced by E2-DSG.

Administration, Oral↗

PubMed2000

Lipoprotein (a) is associated with endothelial function in healthy postmenopausal women.

BACKGROUND: Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. The atherogenic potential of Lp(a) may be by impairment of endothelial function. Objectives. We investigated the relation of Lp(a) plasma levels to endothelium dependent and independent dilatation of the brachial artery in healthy postmenopausal women. METHODS: One hundred and five healthy postmenopausal women aged 52-67 years were included in the study. Endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. RESULTS: Flow mediated dilatation was inversely related to the plasma logLp(a) level. Mean change per unit logLp(a) increase:-2.83% (95% CI: -5.22--0.43). Elevated Lp(a) (>239 mg/l) (upper quartile) was associated with an impaired flow mediated vasodilatation (2.4%+/-1. 2) compared to Lp(a) < or =239 mg/l (5.2%+/-0.7). Adjustment for other cardiovascular risk factors did not change the magnitude of the association. Nitroglycerine-induced vasodilatation was not significantly lower in the high Lp(a) level group, compared to the group with normal levels of Lp(a) (< or =239 mg/l) (8.0+/-1.2 vs. 11.4%+/-0.8). CONCLUSION: Elevated lipoprotein (a) levels are associated with an impaired endothelial function in healthy postmenopausal women, independent of conventional risk factors for cardiovascular disease. Since Lp(a) may be pathogenetically important for early vascular damage, elevated Lp(a) levels might contribute to the increased cardiovascular risk seen in postmenopausal women.

Administration, Sublingual↗

PubMed2000

The effect of hormone replacement therapy on arterial distensibility and compliance in perimenopausal women: a 2-year randomised trial.

A single centre randomised placebo-controlled trial was performed to assess the 2-year effects of hormone replacement therapy compared to placebo on mechanical arterial properties in 99 perimenopausal women recruited from the general population. The trial was double-blind with respect to a sequential combined regimen of oral 17beta-oestradiol and desogestrel (17betaE(2)-D) and the placebo group and open with respect to combination of conjugated equine oestrogens and norgestrel (CEE-N). At baseline, distensibility and compliance of the common carotid artery were measured non-invasively with B-mode ultrasound and a vessel wall movement detector system, and the distensibility coefficient (DC) and compliance coefficient (CC) were calculated. Measurements were repeated after 6 and 24 months. Change in DC and CC in treatment groups was compared to placebo. After 24 months, changes for 17betaE(2)-D compared to placebo were -1.4x10(-3)/kPa (95% CI -4.4; 1.7, P=0.39) for DC and 0. 26 mm(2)/kPa (95% CI -0.01; 0.53, P=0.07) for CC. Changes for CEE-N compared to placebo were 0.4x10(-3)/kPa (95% CI -1.0; 1.9, P=0.79) and 0.11 mm(2)/kPa (95% CI -0.14; 0.37, P=0.40). For systolic blood pressure (SBP), diastolic blood pressure (DBP) and arterial lumen diameter no changes were found. In this study no significant differences in changes in distensibility and compliance were found between perimenopausal women using 17betaE(2)-D or CEE-N and women using placebo after 6 and 24 months.

Adult↗

PubMed1999

Hormone replacement therapy in perimenopausal women and 2-year change of carotid intima-media thickness.

OBJECTIVES: To assess the 2-year effects of a combined regimen of oral 17beta-estradiol and desogestrel (17betaE-D) and a sequential combination of conjugated equine estrogens and norgestrel (CEE-N) on common carotid intima-media thickness and end-diastolic lumen diameter in comparison to placebo in perimenopausal women. METHODS: The study was a single center, randomized, group-comparative, double-blind study with respect to the 17betaE-D and placebo groups and open with respect to CEE-N. After cycle 6, the blind was broken and the trial was continued as an open trial for another 18 months for the active study arms. The study included 121 perimenopausal women recruited from the general population. Common carotid intima-media thickness and end-diastolic lumen diameter were measured at baseline and cycle 24 with B-mode ultrasonography. RESULTS: At cycle 24 small changes in intima-media thickness and lumen diameter were observed. Relative to placebo, changes in intima-media thickness were -0.009 mm [95% CI -0.045; 0.027] for 17betaE-D and -0.016 mm [95% CI -0.055; 0.024] for CEE-N. For end-diastolic lumen diameter the changes were -0.091 mm [95% CI -0.236; 0.055] and -0.125 mm [95% CI -0.820; 0.032] for 17betaE-D and CEE-N, respectively. CONCLUSIONS: In this study among perimenopausal women a significant effect of 17betaE-D and CEE-N on common carotid intima-media thickness and lumen diameter could not be demonstrated. Although the sample size of the present trial is too limited to provide definite conclusions, the direction of the effect is in agreement with evidence from earlier studies on the effects of hormone replacement therapy in postmenopausal women.

Adult↗

PubMed1991

Mode of action of a new class IC drug (ORG 7797) against atrial fibrillation in conscious dogs.

In five chronically instrumented conscious dogs, we studied the antifibrillatory action of the experimental class IC drug Org 7797 ((16 alpha,17 beta)-17-methylamino-oestra-1,3,5(10)-triene-3,16-diol- (Z)-2-butenedioate). Under control conditions, paroxysms of atrial fibrillation were induced by burst pacing (50 Hz; inducibility 100%) and persisted on the average for greater than 3 min. Org 7797 (1, 2, and 3 mg/kg/h) significantly reduced both inducibility and duration of atrial fibrillation to 25 and 10%, respectively. To elucidate the electrophysiologic mechanisms of this potent antifibrillatory action, we measured the effects of Org 7797 on conduction velocity, effective refractory period (ERP), and wavelength of the atrial impulse. Org 7797 decreased atrial conduction velocity significantly by 18-25% and lengthened ERP by 18-29% (pacing 2-5 Hz). The maximal pacing frequency (Fmax) was decreased from 8.3 to 6.2 Hz. During Fmax, Org 7797 decreased the conduction velocity by 23% and lengthened ERP by 75%, resulting in a prolongation of the wave-length from 9.8 +/- 2.3 cm (control) to 13.7 +/- 2.6 cm (3 mg/kg/h; p less than 0.01). These results indicate that the antifibrillatory action of Org 7797 is based on diminution of the physiologic rate-dependent shortening of refractoriness, resulting in a prolongation of the wavelength during maximal heart rates (HRs). This electrophysiologic effect of the drug will decrease the number of multiple wavelets during fibrillation, thus increasing the statistical chance of spontaneous termination of the fibrillatory process.

Animals↗

PubMed1990

Effects of bepridil and diltiazem on ventricular repolarization in angina pectoris.

To examine the time-course and potential predictors of prolongation of ventricular repolarization with the calcium antagonist bepridil, the effects of bepridil (300 to 500 mg/day; n = 45) and diltiazem (180 to 300 mg/day; n = 42) on QT and QTc interval duration were analyzed in a randomized double-blind study in patients with angina pectoris. Electrocardiograms were recorded before and 14, 28, 70 and 112 days after treatment was begun. After 14 days, bepridil prolonged QT interval by 26 +/- 35 ms (range, -60 to 120 ms) and QTc (Bazett's formula) by 17 +/- 33 ms (range, -73 to 107 ms) compared to baseline (both p less than 0.05). QT or QTc did not significantly increase thereafter. However, among the 30 patients who had less than 40 ms QTc prolongation at day 14 compared with baseline, 13 (43%) exceeded this limit on at least 1 of the following visits. Diltiazem did not significantly alter QT or QTc intervals. The absolute change in QTc interval from baseline observed after 14 days of bepridil therapy was inversely proportional to the baseline QTc interval (r = -0.68; n = 42; p less than 0.001). The degree of bepridil-induced QTc prolongation on day 14 correlated with pretreatment RR interval (r = 0.36; n = 42; p less than 0.02). In conclusion, chronic administration of bepridil but not of diltiazem prolongs ventricular repolarization in patients with angina pectoris. The overall effects of bepridil therapy on QT and QTc intervals can be assessed by an electrocardiogram recorded after 14 days of treatment but subsequent measurements may be required in individual patients. A short baseline QTc interval and a slow initial heart rate may be potentially useful predictors of a greater QTc prolongation with bepridil.

Angina Pectoris↗

PubMed1985

Acute effects of intravenous nisoldipine on left ventricular function and coronary hemodynamics.

The hemodynamic effects of nisoldipine were investigated in 16 patients with suspected coronary artery disease who underwent routine cardiac catheterization. Nisoldipine was given intravenously in a dose of 6 micrograms/kg over 3 minutes and measurements made before and after drug administration during spontaneous and matched atrial paced heart rate. During sinus rhythm, nisoldipine produced a significant increase in heart rate (19%, p less than 10(-5]. Left ventricular systolic pressure decreased 28% (p less than 10(-6) and left ventricular end-diastolic pressure did not change significantly (5%, difference not significant). Coronary sinus and great cardiac vein blood flow increased by 21% (p less than 0.02) and 25% (p less than 0.005), respectively, after nisoldipine administration. Simultaneously, mean aortic pressure decreased 33% (p less than 10(-6]; consequently, the global and regional coronary vascular resistances decreased by 50% (p less than 10(-4]. The decreases in global (-8%) and regional (-4%) myocardial oxygen consumption did not reach statistical significance. A 6% (not significant) increase in end-diastolic volume and an 11% (p less than 0.002) decrease in end-systolic volume resulted in an increase of 21% in stroke volume (p less than 10(-4] with a consistent increase in ejection fraction (+16%, p less than 10(-5]. Total systemic vascular resistance was reduced by 30% (p less than 0.0002). During spontaneous heart rate and matched atrial pacing, the time constant of isovolumic relaxation as assessed by a biexponential model, was significantly shortened.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Acute coronary hemodynamic effects of equihypotensive doses of nisoldipine and diltiazem.

The hemodynamic effects of nisoldipine and diltiazem were investigated in two groups of patients undergoing investigation for suspected coronary artery disease. Emphasis was placed on the coronary hemodynamic changes. Approximately equihypotensive doses of these two calcium channel blockers, nisoldipine (6 micrograms/kg) and diltiazem (500 micrograms/kg) were given intravenously. Although both drugs decreased peak systolic pressure by 28% and 24%, respectively, heart rate increased with nisoldipine (68 +/- 9 to 82 +/- 12 bpm) and remained unchanged with diltiazem (70 +/- 9 to 67 +/- 10 bpm). Nisoldipine increased mean coronary sinus blood flow from 146 +/- 40 to 176 +/- 35 ml/min and great cardiac vein flow from 87 +/- 20 to 109 +/- 24 ml/min, producing a significant reduction in the calculated global (from 0.79 +/- 0.2 to 0.43 +/- 0.12 mmHg min/ml) and regional (from 1.43 +/- 0.2 to 0.70 +/- 0.13 mmHg min/ml) coronary vascular resistances. There were no significant flow changes when corrected for heart rate. Global and regional myocardial oxygen consumptions were not significantly altered. Diltiazem had no significant effects on heart rate or global and regional blood flows, although the vascular resistances decreased by 32% and 35%, respectively. Diltiazem reduced global and regional arterio-coronary sinus oxygen differences, resulting in significant decreases in global (from 14.9 +/- 4.7 to 12.1 +/- 2.3 ml/min) and regional (from 5.6 +/- 0.9 to 5.2 +/- 1.2 ml/min) myocardial oxygen consumptions. The major difference between the drugs was in heart rate, despite the similar reductions in aortic pressure. The lack of a positive chronotropic response after diltiazem may explain the reduction in myocardial oxygen consumption.

Adult↗

PubMed1985

Effect of intracoronary thrombolytic therapy on global and regional left ventricular function. A three year experience with randomization.

The effect of myocardial reperfusion on regional left ventricular function has been quantitated by analysis of segmental wall motion in 185 patients enrolled in a randomized trial comparing thrombolysis with conventional treatment in patients with acute myocardial infarction. When analyzing the hemodynamic data on an "intention to treat" basis we found a significant preservation of left ventricular function after thrombolytic therapy when compared to conventional treatment. In addition, the wall motion analysis showed that a significant improvement of regional function in the "infarct zone" was observed in inferior infarction as well as in anterior infarction, although significant changes in regional function of the remote "non infarct zone" were observed at the acute as well as at the chronic stage. However, our follow-up data indicate that as yet it has not been resolved whether this method of treatment does indeed improve prognosis in patients with acute myocardial infarction. Accordingly, we maintain the view that such invasive treatment should not be generally applied until more follow-up data become available from larger randomized trials.

Aged↗

PubMedDate not supplied

Effects of short-term intravenous administration of diltiazem on left ventricular function and coronary hemodynamics in patients with coronary artery disease.

The hemodynamic effects of diltiazem were investigated in 15 patients with suspected coronary artery disease undergoing routine cardiac catheterization. Diltiazem was given in a high dose of 500 micrograms/kg over a period of 5 min and measurements made before and after drug administration during spontaneous heart rate and during matched atrial pacing. Spontaneous heart rate did not change (-5%; NS). Left ventricular (LV) systolic pressure decreased 24% (p less than 10(-6)) and LV end-diastolic pressure (LVEDP) did not change (-5%; NS). During coronary blood flow measurement, mean aortic pressure decreased 30% (p less than 10(-6)) as global (coronary sinus) and regional (great cardiac vein) coronary vascular resistance diminished with no change in coronary blood flow. Myocardial oxygen consumption decreased 19% (p less than 0.02). During matched pacing, although no change occurred in calculated systolic isovolumic indexes of contractility, end-systolic pressure-volume index decreased 15% (p less than 0.05). The time constant of isovolumic relaxation assessed by a biexponential model decreased. No net change occurred in either global or regional wall motion. In summary, high-dose diltiazem was administered safely to patients with coronary artery disease. It is concluded that, at this dose, diltiazem acted as a peripheral and coronary vasodilator. Hemodynamic changes consistent with a direct negative inotropic and chronotropic effect of the drug were observed. Myocardial oxygen consumption decreased with no change in coronary blood flow.

Aged↗