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Biomedical subjects

W Roth

Publications and source records attributed to W Roth.

At least 37 records · Page 2Linked to original sources
PubMed1989

Cardiovascular effects and plasma level profile of pimobendan (UD-CG 115 BS) and its metabolite UD-CG 212 in patients with congestive heart failure after single and repeated oral dosing.

Pimobendan (10 mg on day 1, then 5 mg twice daily for 28 days) was administered orally to nine patients in class III-IV stable congestive heart failure. On day 1, pimobendan appeared in plasma within 30 min, its plasma concentration peaked at 39 +/- 23 ng/ml after 1.5 h, and then decreased with a half-life of 1.44 +/- 0.94 h. Concentrations of its major metabolite UD-CG 212 peaked 3 h after drug intake, at 24 +/- 7 ng/ml. The time course of plasma concentrations was similar on days 1, 2, and 28. Cardiac index increased from 2.2 +/- 0.5 to 2.8 +/- 0.4 L.min-1.m-2 (p = 0.0001) on day 1, from 2.8 +/- 0.5 to 3.4 +/- 0.4 L.min-1.m-2 (p = 0.0032) on day 2, and stayed at 2.7 +/- 0.6 and 2.7 +/- 0.9 L.min-1.m-2 (p = 0.7895) on day 28. On day 1, pulmonary capillary wedge pressure decreased from 16 +/- 7 to 6 +/- 5 mm Hg (p = 0.0001), from 10 +/- 7 to 7 +/- 8 mm Hg (p = 0.0001) on day 2, and from 9 +/- 7 to 5 +/- 3 mm Hg (p = 0.0275) on day 28. Cardiovascular effects of pimobendan were independent of plasma concentrations. All patients improved by at least one NYHA functional class; exercise tolerance increased. No side effect was observed, but two patients died suddenly: Arrhythmogenicity should be ruled out before pimobendan is recommended for treatment of heart failure.

Aged↗
PubMed1989

Correlations between the cardiovascular effects of pimobendan and plasma concentrations of the parent compound and of its major active metabolite, UD-CG 212 CL, in patients with congestive heart failure.

Pimobendan was administered orally (10 mg single dose on day 1, then 5 mg twice daily for 4 weeks) to nine patients with chronic heart failure undergoing hemodynamic monitoring. The time course of changes in plasma concentrations of pimobendan and of its major active metabolite. UD-CG 212 CL, was similar on days 1, 2, and 28. Pimobendan plasma levels peaked 1.5-2.0 h after drug intake: plasma concentrations of UD-CG 212 CL reached a maximum 1 h later; the terminal half-life of pimobendan in plasma varied between 1.44 +/- 0.94 h on day 1 and 1.19 +/- 0.36 h on day 2. Initially, cardiovascular variables changed with increasing plasma drug levels and reached a maximum 4 h after pimobendan intake; later, we found no correlation between plasma concentrations and hemodynamic effects. A steady state of hemodynamic improvement was achieved after 4 weeks of maintenance therapy with pimobendan. Baseline pulmonary capillary wedge pressure dropped from 16 +/- 7 mm Hg on day 1 to 5 +/- 3 mm Hg at noon on day 28 (-69%; p less than 0.001), and baseline cardiac index increased from 2.2 +/- 0.5 L/min/m2 on day 1 to 2.7 +/- 0.9 L/min/m2 on day 28 (+23%; p less than 0.01). Pimobendan is a long-acting drug that effectively improves cardiac performance in patients with chronic congestive heart failure.

Administration, Oral↗
PubMed1988

Anti-IgE autoantibodies in systemic lupus erythematosus. Prevalence and biologic activity.

IgG and IgM autoantibodies directed against IgE were determined in 95 serum samples from 67 patients with systemic lupus erythematosus, by an enzyme-linked immunosorbent assay. IgM anti-IgE autoantibodies were found in 18 patients (27%) and IgG anti-IgE autoantibodies were detected in 23 patients (34%). The specificity of the immunoassay was confirmed by the ability to inhibit binding with IgE myeloma, but not other immunoglobulin isotypes and the demonstration that the reactivity was directed to the Fc epsilon fragment of IgE. The IgG fraction of certain sera with anti-IgE activity was capable of inducing histamine release from control basophils and cutaneous mast cells. Clinical associations with the presence of anti-IgE activity were sought by retrospective chart analysis of 61 patients. Significant correlation was found with articular involvement, lymphadenopathy, and anti-DNA antibodies (P less than 0.05). Anti-IgE autoantibodies are observed in a significant number of patients with systemic lupus erythematosus and may contribute to the pathogenesis of the vascular and articular lesions characteristic of this disease.

Autoantibodies↗
PubMed1988

The influence of homonymous visual field disorders on colour sorting performance in the FM 100-hue test.

An influence of visual field disorders on sorting performance in the FM 100-hue test is reported. Patients with left-sided field disorders performed worse in the conventional testing direction, i.e. from left to right, compared with patients with right-sided defects. Reversing the direction of sorting led, however, to a similar impairment in patients with right-sided field defects. Observations in normals tested under different conditions of hue sorting support the view that the difference obtained cannot be accounted for by a hemisphere difference in colour processing but by the strategy adopted by subjects.

Adolescent↗
PubMed1988

Activity of thyroid hormone-inducible enzymes following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) caused a depletion of serum thyroxine, but paradoxically did not change L-3,5,3'-triiodothyronine (T3) levels in serum of rats. The activities of the thyroid-regulated enzymes alpha-glycerol phosphate dehydrogenase (GPD) and malic enzyme (ME) were determined in livers of normal and thyroidectomized (THX) rats treated with 0.1 to 100 nmol TCDD/kg body weight. Mitochondrial GPD activity did not change significantly as a function of TCDD dose in either normal or THX rats. ME activity was induced by TCDD in a dose-dependent fashion, but only in non-THX animals. The absence of ME induction in THX rats treated with TCDD indicates that TCDD is not intrinsically thyromimetic. The dependence of ME induction on thyroid hormones is much like the thyroid-hormone-dependent, multihormonal induction of ME by insulin and glucocorticoids. However, TCDD had no additive or synergistic effects on induction of ME activity in THX rats fed T3. A 30% decrease in steady-state plasma T3 levels of T3-fed animals treated with TCDD relative to T3-fed controls suggested that T3 catabolism was more rapid in TCDD-treated rats than controls. Thus a thyroid-hormone-dependent, multihormonal interaction is suggested as the basis for induction of ME by TCDD, but a strictly T3-dependent process has not been ruled out.

Administration, Oral↗
PubMed1988

Elevated histamine and tryptase levels in smokers' bronchoalveolar lavage fluid. Do lung mast cells contribute to smokers' emphysema?

Human lung mast cells have been reported recently to contain small amounts of the elastolytic protease present in the neutrophil and implicated in the pathogenesis of alveolar wall destruction in emphysema. Since mast cells are numerous within alveolar walls, release of inflammatory mediators (and possibly elastase) by cigarette smoking could contribute to alveolar injury in this disease. We therefore examined bronchoalveolar lavage (BAL) fluid for the mast cell granule constituents histamine and tryptase. The results, while not conclusive, supported the possibility that cigarette smoking increases secretion of histamine releasing activity by alveolar macrophages with subsequent degranulation of local mast cells. Mast cell discharge of inflammatory mediators (including neutrophil chemotactic factors and perhaps the elastolytic protease) could then participate in the destruction of alveolar walls.

Adult↗
PubMed1988

[Complications following osteosynthesis management of femoral neck fractures with spongiosa locking screws].

Osteosynthesis under pressure using two perforating cancellous bone screws in medial and lateral fractures of the neck of the femur and in some cases also in pertrochanteric fractures of the femur has proved successful, in our opinion, in surgery aimed at preserving the head of the femur, as has been confirmed at our hospital by follow-up studies. A striking fact that came to light during follow-up was that there was a higher percentage of incidence of necroses of the femoral head following Pauwels-I-type fractures. However, in our case it was only one necrosis of the head of the femur in a total of five Pauwels-I-type fractures treated by osteosynthesis. A final judgment can surely be passed only by studying a larger number of cases for a longer period of time. We will, therefore, follow up the fractures of the neck of the femur a few years later by re-examination. As a matter of principle, the aim of surgery in osteosynthesis of a medial femoral neck fracture can be attained by means of the cancellous bone screws. A very important aspect which is most essential for successful surgery is the accurate and controlled introduction of the screws via the guide wire. The infection risk is reduced by the small operative approach. In view of the fact that the follow-up examinations revealed more than 72% well-healed fractures of the neck of the femur, we do not think it necessary to effect any changes in our surgical procedure at the present time.

Bone Screws↗
PubMed1988

[Pharmacokinetics and laxative effect of bisacodyl following administration of various dosage forms].

Since its introduction into the market in 1952, bisacodyl has been successfully used worldwide as a laxative. In discussions on the kinetics and the laxative effect, it is often neglected that results obtained after the administration of the pure compound bisacodyl cannot be transferred to distinctive bisacodyl formulations. The aim of the present investigation is therefore to study the absorption and the plasma level profile and to correlate plasma level profile and laxative effect after the administration of various dosage forms. 12 healthy volunteers were administered with 10 mg bisacodyl as an experimental solution, with an acid resistant, commercially available Dulcolax Dragees (2 x 5 mg) and with a 10 mg Dulcolax suppository. Following glucuronidase cleavage, mean maximum plasma levels of 236.5 +/- 59.2 ng/ml of bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM) were reached after the administration of the solution 1.7 h post administration (p.a.), however, the laxative effect did not occur until 5.7 h +/- 0.7 h p.a. The dominant biological half-life of deconjugated BHPM, the diphenol of bisacodyl which circulated as BHPM-glucuronide, was about 16.5 +/- 4.2 h. The dragee yielded the desired low plasma levels which were between 7 and 47 ng/ml at 4-10 h p.a. In comparison to the solution only 16% were absorbed after the administration of the dragee. The laxative effect started 7.7 h +/- 1.7 h p.a. with no apparent relationship between effect and plasma level. The administration of the suppository resulted 20 +/- 10 min p.a. in a prompt laxative effect, although in 6 out 12 subjects, the plasma levels were below the detection limit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties.

Intravenous infusions of 0.01-0.1 mg X kg-1 X min-1 of pimobendan, a benzimidazole-pyridazinone derivative in pigs with normal coronary circulation caused dose-dependent changes in heart rate (10-35%), left ventricular systolic pressure (-5 to -45%), left ventricular filling pressure (-20 to -40%) but had only a minor effect on the maximum rate of rise of left ventricular pressure (max LVdP/dt; 10-20%). The decrease in mean arterial blood pressure was primarily due to systemic vasodilation; peripheral resistance and cardiac output decreased by up to 40 and 14%, respectively. Vasodilation occurred in several vascular beds, but was particularly pronounced in the adrenals, stomach, small intestine and myocardium. Although the increase in myocardial blood flow favoured the epicardium, vascular conductance in both the endo- and epicardial layers was significantly increased. Myocardial O2 consumption (MVO2) was not affected despite the increase in heart rate. Bolus injections of 0.1-0.5 mg X kg-1 pimobendan produced similar changes in all haemodynamic variables, except max LVdP/dt which now increased by 30-70%. As in the infusion experiments, cardiac output tended to decrease due to a pronounced reduction in ventricular preload probably as a result of venodilation and the consequent reduction in cardiac filling. However, in animals where max LVdP/dt and cardiac output were reduced and pre- and/or after-load were increased by partial occlusion of the left anterior descending coronary artery, pimobendan clearly increased both max LVdP/dt and cardiac output. Pretreatment with propranolol did not modify any of the cardiovascular responses to pimobendan, thereby excluding the involvement of a beta-adrenoceptor mechanism. Pimobendan is thus a compound with vasodilator and positive inotropic properties that improves cardiac output in animals with severe myocardial ischaemia. The finding that the mild tachycardia caused by pimobendan was not accompanied by an increase in MVO2 warrants investigation to evaluate its usefulness in the treatment of heart failure.

Adrenergic beta-Antagonists↗
PubMed1986

[Keratoacanthoma on the left cheek of Galileo Galilei].

In an oil painting from the School of Sustermans, which can be seen in the Palazzo Pitti in Florence, we diagnosed the alterations typical of a keratoacanthoma in the left cheek-bone area of the portrayed Galileo Galilei.

Astronomy↗
PubMed1985

A tubal plug and clip method for female sterilization.

Animal studies using rabbits, stumptailed macaques monkeys, and baboons demonstrate that the tubal plug and clip device is an effective and safe method for female sterilization in these animal models. The devices were placed in 18 baboons that were bred regularly for six to 18 months without conception. Ten of these 18 animals conceived within 12 months after removal of the devices and carried normal pregnancies without any other surgical procedure. Six of the ten animals conceived and carried a second pregnancy for a total of 16 successful pregnancies. The expected pregnancy rate for baboons is 64.9% per year so that the 55.6% success rate of reversal and 16 total pregnancies clearly represents a high degree of reversibility for the method in this animal species.

Animals↗