Clinical safety and efficacy of celiprolol.

The management of essential hypertension requires therapeutic selections that are not only effective in reducing diastolic blood pressure but are also tailored to the individual patient, with minimal effect on patient demographics, concurrent illnesses, and cardiovascular risk factors. Celiprolol hydrochloride is a new highly cardioselective vasodilating beta-adrenoceptor antagonist that has been proven effective and safe for the treatment of essential hypertension. It is comparable to other therapies in blood pressure control while demonstrating an excellent safety profile, favorable hemodynamic activity, and minimal effects on other cardiovascular risk factors. Celiprolol may offer the physician a unique therapeutic alternative.

Evaluation of celiprolol, a new cardioselective beta 1-adrenergic blocker with vasodilating properties, in the treatment of mild to moderate hypertension in the elderly.

Celiprolol hydrochloride is a cardioselective beta 1-adrenergic antagonist with partial agonist activity. The studies discussed were designed to assess celiprolol's pharmacokinetic disposition, its efficacy versus placebo and other beta blockers, its relative safety profile, and its therapeutic ratio in the elderly population. The results of a postmarketing surveillance study are also presented. Pharmacokinetic results indicate good dose-related bioavailability in the elderly, no accumulation on multiple dosing, and pharmacokinetics equivalent to those in a younger age group. Celiprolol effectively lowers blood pressure in elderly patients with mild to moderate hypertension, resulting in reductions of 12-15 mmHg and 8-11 mmHg in systolic and diastolic blood pressures, respectively. A clinically insignificant reduction in resting pulse rate is observed with celiprolol treatment. Its adverse experience profile is equivalent to that of placebo, and the incidence of beta-blocker-associated side effects is lower compared with that of atenolol and propranolol. Celiprolol also effectively controlled hypertension in the elderly in the postmarking surveillance study. Collectively, the results of these studies demonstrate that the pharmacokinetics and efficacy of celiprolol in the treatment of mild to moderate hypertension are equivalent in younger and older populations, and that the therapeutic ratio (i.e., efficacy/safety) of celiprolol is superior to that of atenolol and propranolol in the elderly.

Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies.

Conventional clotting factor concentrates have, until recently, been "of intermediate purity," containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients.

Safety profile of celiprolol.

Celiprolol hydrochloride is a highly cardioselective beta1-adrenergic antagonist with a unique pharmacologic profile. The adverse experience safety data derived from 18 double-blind trials (n = 2884) were evaluated. The results demonstrated a wide margin of safety for celiprolol over the recommended dosage range of 200 to 600 mg once daily. Celiprolol exhibited an adverse experience profile similar to that of placebo and resulted in a lower incidence of bradycardia and age-associated increases in adverse event rates compared with atenolol and propranolol.

Transvaginal and transabdominal sonography: prospective comparison.

Transvaginal (TV) and transabdominal (TA) sonography were compared in a prospective study. A total of 230 examinations (126 pelvic, 104 pregnancy) were performed on 215 patients, ranging in age from 14 to 80 years. The improved anatomic detail on TV scans yielded new information in 138 (60%) examinations and better visualization of pelvic structures in 51 (22%) examinations. There was no important difference in diagnostic information provided by the two imaging modalities in 36 (16%) cases, and TV images were worse in five (2%). The clinical diagnosis was altered on the basis of TV sonographic findings in 54 (24%) cases and confirmed with certainty in 166 (72%). Diagnostic problems posed by TA scanning were not resolved by TV scanning in ten (4%) instances. Statistical analysis indicated that TV scanning was significantly better than TA scanning in the visualization of gestational sac contents (P less than .005), detection of fetal heart motion (P less than .001), and evaluation of the endometrial canal in the retroverted or retroflexed uterus (P less than .001). TV scanning was significantly better than TA scanning in visualization of the ovaries in patients with uterine leiomyomas (P less than .005) but not significantly better in peri- and postmenopausal patients (P greater than .05).

Celiprolol--overview of 6 years of clinical trials experience.

The results of an extensive pre-clinical and clinical research programme indicate that celiprolol is a safe and effective treatment for both hypertension and angina pectoris. Celiprolol is well absorbed, is largely unmetabolized, and is excreted equally in the urine and bile. As a result of this pharmacokinetic profile celiprolol can be safely administered to the elderly and to patients with renal or hepatic impairment. Haemodynamic studies indicate that celiprolol lowers arterial blood pressure, and decreases both renal vascular resistance and peripheral vascular resistance. Celiprolol does not depress myocardial function, neither does it induce bronchoconstriction in asthmatic patients. Weak alpha 2-adrenoceptor antagonism, combined with beta 2-adrenoceptor agonism are thought to contribute to these properties. The antihypertensive efficacy of celiprolol, 200 mg/day, is comparable to that of propranolol, atenolol and nadolol. Moreover, the actions of celiprolol last for 24 h, and are accompanied by less resting bradycardia than that seen with other beta-blockers. The anti-anginal efficacy of celiprolol is similar to that of atenolol, propranolol and metoprolol. In addition, celiprolol decreases the ventricular rate in patients with atrial tachyarrhythmias. This effect results from its ability to slow atrioventricular conduction. Celiprolol is generally very well tolerated.

Effects of hydrocortisone and aspirin on protein synthesis and post-translational protein modification in cultured cells.

Arginyl-tRNA transferase is suggested to function as a post-translational modifier of proteins through the addition of arginine to the NH2-terminus of specific acceptor proteins. Both hydrocortisone and aspirin produced an age-dependent stimulation of protein synthesis in normal human fibroblasts (IMR90), while producing an inhibition of protein synthesis in SV40 virus-transformed IMR90 cells. The effect of aspirin was confined primarily to the cytoplasmic compartment, whereas hydrocortisone produced its effect at both cytoplasmic and nuclear levels. Neither hydrocortisone nor aspirin had a direct effect on arginyl-tRNA transferase activity in vitro; however, hydrocortisone resulted in a marked increase in the availability of chromosomal proteins subject to modification by arginyl-tRNA transferase. This stimulatory effect was attenuated by increasing culture age. The modified chromosomal proteins were found to be dissociated from native chromatin, suggesting that arginylation either triggered their release or prevented reassociation with chromatin thereafter. Hydrocortisone produced a moderate decrease in the availability of chromosomal proteins for arginylation in SV40 virus-transformed cells, and this effect was not modulated by aging phenomena.

Effect of temperature on normal and SV40-transformed human fibroblasts.

The effect of a temperature shift from low (36 degrees C) to high (40 degrees C) temperature on human fibroblasts (IMR90) at various population doubling levels and IMR90 cells transformed by SV40 virus infection at a population doubling level of 30 (SV40/IMR90) was examined. Both IMR90 and SV40/IMR90 cells showed a decrease in cell saturation density at confluency, whereas an increase in population doubling time and protein content was noted when the cells were shifted up to 40 degrees C from 36 degrees C. The modification of IMR90 chromosomal proteins by arginyl-tRNA transferase was increased by the temperature shift, whereas NH2-terminal arginylation of SV40/IMR90 chromatin was not altered. Similarly, no appreciable change in 2-deoxyglucose uptake was noted with SV40/IMR90 cells at either temperature, although 2-deoxyglucose uptake by IMR90 cells was increased by the temperature shift. Additionally, the rate of 2-deoxyglucose uptake showed no difference between IMR90 and SV40/IMR90 cells. The above results support previous findings that environmental alterations, such as temperature shift can cause acceleration of cellular senescence. These findings also imply that cellular senescence remains fixed when viral transformation occurs and is rendered refractory to further age-associated alterations.