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Biomedical subjects

G Weidinger

Publications and source records attributed to G Weidinger.

At least 37 records · Page 2Linked to original sources
PubMed1999

A more mature phenotype of blood mononuclear phagocytes is induced by fluvastatin treatment in hypercholesterolemic patients with coronary heart disease.

Monocytes are recruited as the principal inflammatory cells into the atherosclerotic lesion. In a previous study we demonstrated that a low HDL-cholesterol and the apo E4 allele are associated with an increased proportion of blood monocytes that are characterized by a high expression of Fcgamma-RIIIa (CD16), a dim expression of the lipopolysaccharide (LPS) receptor (CD14) and a high expression of beta1- and beta2-integrins (Rothe et al. Arterioscler Thromb Vasc Cell Biol 1996;16:1437-1447). In this study, 79 hypercholesterolemic patients were treated either with the HMG CoA reductase inhibitor fluvastatin in combination with diet or with placebo and diet in a double-blind and randomized multicenter study, and monitored for the potential effects on the phenotype of peripheral blood monocytes. At baseline, in the whole group of hypercholesterolemic patients the population size of these more mature monocytes (CD14dimCD16+) was positively correlated to triglyceride (P = 0.003) and total serum cholesterol levels (P = 0.012) confirming our previous study. Fluvastatin treatment for 52 weeks was associated with a 24.2% reduction in LDL-cholesterol (P < 0.001) as well as a 40.7% decrease in the expression density of CD14 on all monocytes (P = 0.027). A 24.5% decrease (P < 0.001) of the population of less differentiated CD14brightCD16- monocytes and an 83.1% increase (P = 0.029) of the population of more differentiated CD14dimCD16+ monocytes further confirmed this modification of the phenotype of peripheral blood monocytes. The positive pre-study correlation of the CD14dimCD16+ monocyte subset to the serum cholesterol concentration, but inverse changes of both parameters under fluvastatin therapy, in conclusion indicate that fluvastatin exerts an as yet uncharacterized immunomodulatory effect on either monocyte maturation and differentiation, or extravasation which may also depend on the endothelial phenotype that is independent of the change in serum lipids.

Adult↗
PubMed1999

The effect of fluvastatin on cardiac events in patients with symptomatic coronary artery disease during one year of treatment.

The primary objective of the present study was to investigate the cholesterol-lowering effect of fluvastatin on the incidence of cardiac events in hyperlipidaemic patients with symptomatic, clinically-diagnosed (exercise-ECG) coronary heart disease (CHD) during 1 year of treatment. Exercise tolerance, incidence of angina pectoris episodes, use of anti-anginal medication and intimal-medial-thickness (IMT subgroup) of the A. carotis were secondary endpoints. In the double-blind trial a total of 365 male and female patients with stable symptomatic CHD and a low-density lipoprotein cholesterol (LDL-C) above 160 mg/dl on a lipid-lowering diet were randomised to fluvastatin 40 mg (o.a.d. or b.i.d.) or placebo for 1 year. Fluvastatin lowered total cholesterol by 17% and LDL-C by 27%. There was a significantly lower incidence of cardiac events (cardiac death, nonfatal myocardial infarction, unstable angina pectoris) in the fluvastatin group (3 events) as compared to the placebo group (10 events) (P < 0.05). Exercise tolerance improved and the incidence of angina pectoris episodes decreased in both groups, but more pronounced on fluvastatin (n.s.). Exercise-ECG discontinuation due to angina pectoris and ST-segment depression decreased in the fluvastatin group by 55.6 and 70.9%, respectively, and in the placebo group by 39.6 and 46.5% (n.s.). At baseline, a subgroup of 76 patients showed a mean IMT value of 0.73 mm which remained uninfluenced in the fluvastatin and the placebo groups. Fluvastatin was safe and well tolerated. In conclusion, patients with symptomatic CHD get cardiovascular benefit from lipid-lowering therapy with fluvastatin even during the first year of treatment.

Adult↗
PubMed1999

Short duration treatment with terbinafine for tinea capitis caused by Trichophyton or Microsporum species. The Study Group.

Thirty-five patients with mycologically proven scalp infections were enrolled in a randomized, double-blind clinical trial with oral terbinafine (dose adjusted according to patient weight) for either 1 or 2 weeks. Patients were observed for 12 weeks; after 4 weeks, non-responders were offered an additional 4 weeks of treatment followed by a second observation period. The causative organisms were Microsporum canis (n = 12), Trichophyton tonsurans (n = 12) and other Trichophyton spp. (n = 11). The Trichophyton infections were treated effectively in five of nine (56%) patients treated for 1 week and 12 of 14 (86%) patients treated for 2 weeks. Three of the non-responders were treated for an additional 4 weeks, and one responded. In the Microsporum group only one of seven patients treated for 1 week and none of five treated for 2 weeks responded. However, treatment was effective in four of six (66%) patients treated for an additional 4 weeks. Mild to moderate adverse events believed to be drug related occurred in four patients in each of the two groups. Terbinafine is well tolerated, and requires 2 weeks of treatment in most patients with Trichophyton scalp infections and 4 weeks or more in Microsporum scalp infections, to achieve a successful clinical and mycological response.

Adolescent↗
PubMed1999

Efficacy and tolerability of terbinafine 1% topical solution used for 1 week compared with 4 weeks clotrimazole 1% topical solution in the treatment of interdigital tinea pedis: a randomized, double-blind, multi-centre, 8-week clinical trial.

In this double-blind clinical trial 429 patients (217 terbinafine and 212 clotrimazole) were randomized to receive twice daily terbinafine 1% topical solution for 1 week followed by a vehicle application for 3 weeks, or 1% clotrimazole solution for 4 weeks. Patients were evaluated clinically and mycologically at baseline and then at weeks one, two, four (end of treatment), and eight (end of follow-up). To be evaluable the patient needed to have a positive culture for a dermatophyte and positive KOH microscopy and a clinical diagnosis of tinea pedis (interdigital type) at baseline. Effective treatment of tinea pedis was recorded in 181 of 217 (83%) of patients treated for 1 week with terbinafine 1% solution and 174 of 212 (82%) of patients treated for 4 weeks with clotrimazole 1% solution. Mycological cure and disappearance of signs and symptoms were similar at each assessment visit in the two groups. In the subgroup of patients without any protocol violation the mycological cure rate was 95% (164 of 173) with terbinafine solution and 91% (159 of 174) with clotrimazole solution (P = 0.05). Adverse events believed to be drug-related occurred in 13 patients in the terbinafine group and 11 in the clotrimazole group (4 to 5% in each group). The events were primarily local skin reactions of mild to moderate intensity. It can be concluded that terbinafine 1% solution used for 1 week to treat tinea pedis is well tolerated and at least as effective as clotrimazole 1% solution used for 4 weeks.

Administration, Topical↗
PubMed1999

Identification of tissues and patterning events required for distinct steps in early migration of zebrafish primordial germ cells.

In many organisms, the primordial germ cells have to migrate from the position where they are specified towards the developing gonad where they generate gametes. Extensive studies of the migration of primordial germ cells in Drosophila, mouse, chick and Xenopus have identified somatic tissues important for this process and demonstrated a role for specific molecules in directing the cells towards their target. In zebrafish, a unique situation is found in that the primordial germ cells, as marked by expression of vasa mRNA, are specified in random positions relative to the future embryonic axis. Hence, the migrating cells have to navigate towards their destination from various starting positions that differ among individual embryos. Here, we present a detailed description of the migration of the primordial germ cells during the first 24 hours of wild-type zebrafish embryonic development. We define six distinct steps of migration bringing the primordial germ cells from their random positions before gastrulation to form two cell clusters on either side of the midline by the end of the first day of development. To obtain information on the origin of the positional cues provided to the germ cells by somatic tissues during their migration, we analyzed the migration pattern in mutants, including spadetail, swirl, chordino, floating head, cloche, knypek and no isthmus. In mutants with defects in axial structures, paraxial mesoderm or dorsoventral patterning, we find that certain steps of the migration process are specifically affected. We show that the paraxial mesoderm is important for providing proper anteroposterior information to the migrating primordial germ cells and that these cells can respond to changes in the global dorsoventral coordinates. In certain mutants, we observe accumulation of ectopic cells in different regions of the embryo. These ectopic cells can retain both morphological and molecular characteristics of primordial germ cells, suggesting that, in zebrafish at the early stages tested, the vasa-expressing cells are committed to the germ cell lineage.

Animals↗
PubMed1998

Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients: a randomized, placebo-controlled, double-blind study.

BACKGROUND: Impaired endothelium-dependent vasodilation is an early sign of atherosclerosis in hypercholesterolemic patients. We hypothesized that lipid-lowering therapy can improve endothelial function and that this effect is mainly mediated by increased bioavailability of nitric oxide (NO). METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, we studied 29 patients (age, 50+/-12 years) with hypercholesterolemia (LDL cholesterol > or = 160 mg/dL) randomly assigned to receive either fluvastatin (40 mg twice daily; 17 patients) or placebo (12 patients). Forearm blood flow was measured by plethysmography before and after 24 weeks of treatment. Endothelium-dependent vasodilation was assessed by intra-arterial infusion of acetylcholine (ACh; 3, 12, 24, and 48 microg/min) and basal NO synthesis rate by intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA; 1, 2, and 4 micromol/min). Simultaneous intra-arterial infusion of L-NMMA (4 micromol/min) and ACh (12, 24, and 48 microg/min) was used to test whether any increase in endothelium-dependent vasodilation after lipid-lowering therapy could be blocked by this NO synthase inhibitor. Endothelium-dependent vasodilation improved significantly after 24 weeks of lipid-lowering therapy compared with before therapy (ACh 24 microg/min: 240+/-34% before versus 347+/-50% after therapy; P< or =0.01) and placebo (changes between after and before therapy with ACh 24 microg/min: 108+/-39% for fluvastatin versus -26+/-32% for placebo; P< or =0.05). This improvement in endothelium-dependent vasodilation could be blocked by simultaneous administration of L-NMMA (ACh 24 microg/min plus L-NMMA 4 micromol/min: 170+/-69% before versus 219+/-47% after treatment; P=NS). CONCLUSIONS: Lipid-lowering therapy with fluvastatin can improve disturbed endothelial function in hypercholesterolemic patients compared with placebo. This improvement is mediated by increased bioavailability of NO.

Acetylcholine↗
PubMed1998

Anterior specification of embryonic ectoderm: the role of the Xenopus cement gland-specific gene XAG-2.

In a search for novel developmental genes expressed in a spatially restricted pattern in dorsal ectoderm of Xenopus we have identified XAG-2, a cement gland-specific gene with a putative role in ectodermal patterning. XAG-2 encodes a secreted protein, which is expressed in the anterior region of dorsal ectoderm from late gastrula stages onwards. Activation of XAG-2 transcription is observed in response to organizer-secreted molecules including the noggin, chordin, follistatin and cerberus gene products. Overexpression of XAG-2 but not of the related cement gland marker XAG-1 induces both cement gland differentiation and expression of anterior neural marker genes in the absence of mesoderm formation. Further, we show that XAG-2 signaling depends on an intact fibroblast growth factor (FGF) signal transduction pathway and that XAG-2-induced anterior neural fate of ectodermal cells can be transformed to a more posterior character by retinoic acid. Based on these findings we propose a role for XAG-2 in the specification of dorsoanterior ectodermal fate, i.e. in the formation of cement gland and induction of forebrain fate of Xenopus.

Amino Acid Sequence↗
PubMed1998

Efficacy and toxicity of 2-Chlorodeoxyadenosine (Cladribine)--2 h infusion for 5 days--as first-line treatment for advanced low grade non-Hodgkin's lymphoma.

2-Chlorodeoxyadenosine (Cladribine) is a new purine analogue with high activity in pretreated low grade non-Hodgkin's lymphoma (NHL). To evaluate the efficacy of this drug in untreated patients with advanced NHL, we performed a prospective multicentre trial. Cladribine (0.12 mg/kg) was administered intravenously daily for 5 consecutive days in an out-patient setting. The treatment was repeated every 28 days for four cycles. Included were patients with a histological diagnosis of low grade NHL according to the Kiel classification and stage III or IV disease. Stage II patients were included when radiotherapy had failed. 55 patients were entered into the study. 50 patients were evaluable. The remission rate was 44/50 (88%; 95% confidence interval 82-100%), including complete remissions (CR) in 14 (28%) patients. Only 2 patients showed progression while on Cladribine treatment. The estimated overall survival, and time to treatment failure (TTF) were 85% and 51%, respectively, after a median observation time of 92 weeks. 11 (22%) patients showed grade 3 or 4 toxicity according to the WHO grading. Haematological toxicity was responsible for 86% of the overall toxicity and 100% of grade 3 and 4 toxicity. 7 patients (14%) had an infection, two of which were opportunistic. 12 (24%) patients did not experience any toxicity during the treatment. The results of this study clearly demonstrate the safety and considerable activity of this regimen. Cladribine is very effective even at lower doses than have been used so far.

Adult↗
PubMed1998

The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion.

Topical SDZ ASM 981 has been found to be highly effective in preclinical models of T-cell-mediated skin disease. T cell activation is crucial in the pathogenesis of psoriasis. It has been hypothesized that SDZ ASM 981 may prove to be an effective treatment for chronic plaque psoriasis. Therefore, the study objective was to determine the efficacy, tolerability and safety of the new topical macrolactam, SDZ ASM 981, for chronic plaque psoriasis. Ten patients with chronic plaque-type psoriasis were treated with SDZ ASM 981 (0.3% and 1.0%), the corresponding ointment base (placebo) and open-labelled clobetasol-17-propionate ointment (0.05%) in a randomized, double-blind, within-subject comparison for 2 weeks using the microplaque assay. Evaluation was performed by daily determination of clinical scores for erythema and induration. The results of the study showed that, after 2 weeks of treatment, total scores described by 92% for clobetasol, by 82% for 1 SDZ ASM 981, by 63% for 0.3% SDZ ASM 981 and by 18% for the ointment base (placebo). No adverse drug effects were seen in any patient throughout the study. We conclude from our results that the new macrolactam SDZ ASM 981 (1%) is similar to clobetasol-17-propionate (0.05%) in plaque-type psoriasis when applied topically under occlusion for 2 weeks using the microplaque assay.

Administration, Topical↗
PubMed1998

Conversion of psoriasis patients from the conventional formulation of cyclosporin A to a new microemulsion formulation: a randomized, open, multicentre assessment of safety and tolerability.

OBJECTIVE: To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun (SIM). METHODS: In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse. RESULTS: The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups. CONCLUSIONS: If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.

Adolescent↗
PubMed1997

Effects of octreotide treatment on restenosis after coronary angioplasty: results of the VERAS study. VErringerung der Restenoserate nach Angioplastie durch ein Somatostatin-analogon.

BACKGROUND: The VERAS study (VErringerung der Restenoserate nach Angioplastie durch ein Somatostatin-analogon [Prevention of Restenosis Following Angioplasty With a Somatostatin Analogue]) was a placebo-controlled trial to evaluate the effects of octreotide for the prevention of restenosis after coronary angioplasty. Octreotide is a somatostatin analogue with antiproliferative properties on smooth muscle cell growth in vitro that limits myointimal thickening of arteries in balloon injury models. METHODS AND RESULTS: Patients received either octreotide or placebo, starting 1 hour before angioplasty and continued for 3 weeks. The minimal luminal diameters before and after angioplasty and at 6-month follow-up were analyzed with a digital quantitative algorithm. Of the initial 274 patients recruited, 217 (108 in the octreotide group and 109 in the placebo group) could be analyzed after a complete 6-month evaluation: the minimal luminal diameters were 1.67+/-0.57 mm in the octreotide-treated group and 1.66+/-0.64 mm in the placebo group (two-paired P=.70), and the relative losses were 0.16+/-0.22 and 0.13+/-0.21 (two-paired P=.27). The restenosis rates were also identical in both treatment groups: final diameter stenosis > or =50% (34.3% versus 33.9%, two-paired P=1.0), loss of > or =50% of the initial gain (34.3% versus 33.9%, two-paired P=1.0), and absolute reduction of minimal luminal diameter >0.72 mm (29.6% versus 24.8%, two-paired P=.45). Likewise, there was no difference with regard to the incidence of clinical events (death, myocardial infarction, bypass operations, reintervention). Octreotide was well tolerated, with the exception of gastrointestinal side effects, which were three times more common than in the placebo group. CONCLUSIONS: Octreotide did not reduce the angiographically determined restenosis rate or the incidence of major clinical events after coronary angioplasty.

Adult↗
PubMed1997

A member of the Met/HGF-receptor family is expressed in a BMP-4-like pattern in the ectoderm of Xenopus gastrulae.

The importance and involvement of growth factors and their corresponding receptors in embryonic induction has been more and more recognized during the past decade, in particular by loss-of-function experiments using dominant negative receptors. Here, we report the isolation of XHR, a Xenopus receptor-type tyrosine kinase, with homology to members of the Met/hepatocyte growth factor (HGF)-receptor family. Sequence comparison of XHR with other members of the Met/HGF-receptor family as well as in situ expression analyses suggest that XHR represents a novel member of this family of receptor-type tyrosine kinases. As could be shown by whole-mount in situ analysis, XHR transcripts are first expressed in the entire ectoderm at the onset of gastrulation. As gastrulation proceeds, XHR-transcription is turned off in cells induced by dorsal mesoderm to form neural tissue and thus, becomes predominantly confined to prospective epidermis. The strikingly similar expression patterns of XHR and Bone Morphogenetic Protein-4 (BMP-4), an inducer of epidermis and inhibitor of neural development, suggest an involvement of XHR signalling in the early cell-fate decision of ectodermal cells to form either neural derivatives or epidermis.

Animals↗
PubMed1997

Effects of fluvastatin therapy on lipids, antioxidants, oxidation of low density lipoproteins and trace metals.

OBJECTIVE: Oxidation of low density lipoproteins (LDL) is thought to be an important step in the development of atherosclerosis. Trace metals are involved in oxidative processes. It was of interest to determine whether lipid-lowering therapy with fluvastatin, a potent HMGCoA reductase inhibitor, affected LDL oxidation and trace metal levels. METHODS: Twenty hypercholesterolemic patients were treated with fluvastatin (40 mg twice daily) or placebo for 8 weeks in a double-blind, randomized study. LDL composition, antioxidants and oxidizability as well as plasma zinc, copper, selenium and manganese concentrations were investigated. RESULTS: After fluvastatin treatment, total cholesterol was reduced by 24%, triglycerides fell by 26% and plasma Zn fell by 8%. Cu, Se and Mn changed insignificantly. LDL were separated by ultracentrifugation. LDL were reduced by 18%, LDL-C by 29% and LDL-TG by 19%. The concentrations of alpha-tocopherol and retinol in LDL changed insignificantly. LDL preparations were incubated with copper ions (204 mumol.1(-1) LDL-C/3.2 mumol.1(-1) Cu) and formation of conjugated dienes was monitored at 234 nm for 5 h. Treatment with fluvastatin caused a reduction of diene production by 16% and of diene production rate by 14%, effects being significantly different from placebo (P = 0.02). The change of the lagtime did not reach significance; however, it was positively correlated with the change in LDL alpha-tocopherol. In the placebo group, no significant effects were observed. CONCLUSION: Fluvastatin therapy had lipid-lowering and antioxidative effects.

Anticholesteremic Agents↗
PubMed1997

Is endothelial function of the radial artery altered in human essential hypertension?

There is controversy over whether endothelial function is impaired in human essential hypertension. All studies to date have used measurements of forearm blood flow by plethysmography to assess endothelium-dependent vasodilation and endothelial function. In contrast to these studies, which have focused on resistance vessels, we have determined what effects the endothelium has on underlying smooth muscle cells in conduit arteries by measuring arterial compliance of the radial arteries (change in diameter of radial artery over pressure for each arterial pulse). In 13 normotensive healthy subjects and 11 young patients with essential hypertension, arterial compliance of the radial artery was assessed directly with a new high-precision ultrasonic device (NIUS 02) after infusion of acetylcholine (endothelium-dependent response) or sodium nitroprusside (endothelium-independent response). Arterial compliance of the radial artery was similar at baseline and with increasing doses of acetylcholine and sodium nitroprusside in normotensive and in hypertensive subjects. The increase in arterial compliance from baseline at each individual concentration of acetylcholine and sodium nitroprusside was the same in both normotensive and hypertensive subjects. However, after a single oral dose of a combination of the angiotensin converting enzyme inhibitor spirapril and the calcium entry blocker isradipine, the increase in arterial compliance in response to the maximum dose of intraarterial acetylcholine was enhanced in normotensives (0.38 +/- 1.23 to 0.76 +/- 1.01 mm2/mm Hg x 10(-3), P < .05), but not in hypertensives (+0.41 +/- 1.26 to 0.36 +/- 1.31 mm2/mm Hg x 10(-3), not significant), and differed significantly between normotensive and hypertensive subjects (P < .05). Thus, pharmacologic stimulation disclosed a blunted response of endothelium-dependent action in the arterial compliance of the conduit arteries in hypertensive subjects. This suggests an impaired endothelial function reserve in persons with essential hypertension.

Acetylcholine↗
PubMed1997

Impact of alpha- versus beta-blockers on hypertensive target organ damage: results of a double-blind, randomized, controlled clinical trial.

In hypertensive disease, the extent of target organ damage determines the prognosis. We conducted a 6-month, double-blind randomized study to compare the effects of an alpha1-adrenoreceptor blocker (bunazosin) with those of a beta1-adrenoreceptor blocker (metoprolol) on early hypertensive target organ damage at a similar level of blood pressure reduction. The study consisted of 43 patients (29 men and 14 women) of varying ages (mean age 52 +/- 9 years) with essential hypertension World Health Organization stage I-II. Both the alpha- and the beta-blocker lowered blood pressure to a similar extent measured by 24-h blood pressure monitoring. The left ventricular mass was comparably reduced in both cohorts (alpha-blocker 284 +/- 80 v 259 +/- 67 g, P < .05, beta-blocker 282 +/- 74 v 254 +/- 70 g, P < .05). Treatment with the alpha-blocker led to reduced total peripheral resistance (22.9 +/- 8.0 v 19.9 +/- 5.3 U, P < .05), whereas therapy with the beta-blocker resulted in an elevated total peripheral resistance (25.5 +/- 8.4 v 28.5 +/- 9.3 U, P < .10; P < .05 for the difference in both groups). Renal plasma flow remained constant in the alpha-blocker treated group but decreased in the beta-blocker treated group (508 +/- 141 v 477 +/- 134 mL/min/1.73 m2, P < .05). Glomerular filtration rate as measured by inulin clearance tended to increase after treatment with the alpha-blocker (112 +/- 20 v 115 +/- 18 mL/min/1.73 m2, P < .10) in accordance with a decrease of serum creatinine (1.00 +/- 0.14 v 0.93 +/- 0.12 mg/dL, P < .001). Plasma cholesterol and LDL cholesterol was lowered after treatment with the alpha-blocker (238 +/- 48 v 312 +/- 37 mg/dL; P < .001, and 153 +/- 32 v 130 +/- 25 mg/dL; P < .05) while remaining unchanged in group treated with the beta-blocker. Left ventricular hypertrophy was similarily reduced with alpha- and with beta-blockade at a comparable reduction of 24-h blood pressure. Alpha-blockers effected a more favorable renal and systemic hemodynamic profile than beta-blockers, but only long-term prospective studies will answer the question whether these hemodynamic effects result into a better cardiovascular prognosis.

Adrenergic alpha-Antagonists↗
PubMed1997

Effect of bunazosin and atenolol on glucose metabolism in obese, nondiabetic patients with primary hypertension.

Antihypertensive drugs, recommended by the World Health Organization for use in monotherapy, exert different effects on glucose and lipid metabolism. In our study we compared the effects of the beta-blocker atenolol (AT) and the alpha1-blocker bunazosin (BU) on glucose metabolism. The doses administered were chosen to produce similar antihypertensive effects with both drugs. The study was conducted as a bicenter, parallel, controlled, and double-blind study. All patients suffered from mild to moderate primary hypertension, were obese (body mass index > 26 kg/m2), but were nondiabetic. After a drug-free period of 4 weeks, patients were treated either with 6 and 12 mg of bunazosin (n = 15) or with 50 and 100 mg of atenolol (n = 17) once daily for 12 weeks. Glucose metabolism was measured by the iv glucose tolerance test (GTT) and the euglycemic hyperinsulinemic clamp test. The results show a similar blood pressure reduction with both drugs. However, their effects on glucose metabolism were significantly (p < 0.05) different: The area under the curve (AUC) of glucose in the iv GTT increased 26.8% during atenolol treatment but decreased 30% during bunazosin treatment. The same influence on the AUC of insulin was observed [AT +478.5 +/- 441.8 (+22%) vs. BU, -588.5 +/- 411.1 (-22%)]. Similar changes were found in the glucose clamp test. The metabolic clearance rate increased 11.4% during bunazosin use and decreased 8.4% during atenolol use to the same degree that the insulin sensitivity index changed (BU +13.2% vs. AT -21.9%). The differences between the two treatment regimes were statistically significant (p < 0.05). These results in obese hypertensives confirm the well-known negative effects of beta-blockers on glucose metabolism. Additionally, they demonstrate that an alpha1-blocker such as bunazosin develops the same blood pressure-lowering effect as beta-blockers, but with a significantly better profile with regard to glucose metabolism. Therefore, the use of alpha1-blockers can be recommended for obese hypertensives without any special care for glucose metabolism.

Adrenergic alpha-Antagonists↗
PubMed1997

Evaluation of the efficacy and tolerability of a low-dose combination of isradipine and spirapril in the first-line treatment of mild to moderate essential hypertension.

To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor, a fixed combination of isradipine 2.5 mg plus the ACE inhibitor spirapril 3 mg was compared with its components, with the full-dose monotherapies (isradipine 5 mg or spirapril 6 mg), and with placebo. After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period, 405 patients with a diastolic blood pressure (DBP) between 100 and 114 mmHg were randomly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms. In patients whose blood pressure was not normalized (defined as DBP< or =90 mmHg) after 6 weeks of treatment, the dosage of either medication was doubled or, in the placebo group, was switched to the fixed combination. After week 6, the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing (trough) for the fixed combination or the monotherapies isradipine 5 mg, isradipine 2.5 mg, spirapril 6 mg, spirapril 3 mg, and placebo were 10.4/8.7, 10.0/9.4, 6.5/6.7, 10.0/8.3, 7.0/5.8, and 2.2/4.7 mmHg, respectively. The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies, thus showing an additive effect of low-dose isradipine and spirapril. In terms of tolerability, the lowest rate of any adverse events was found in the combination group. In this group, typical adverse events of calcium antagonists, such as headache, flushing, ankle edema, or palpitations, were observed only in 5%, 2%, 1%, and 0%, respectively, dry cough, considered typical for ACE inhibitors, was observed in only 1% of the combination group. In conclusion, the low-dose components isradipine 2.5 mg and spirapril 3 mg were shown to have an additive effect when combined, exerting a blood pressure-lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the standard doses. Thus, low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.

Adult↗