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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

[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

[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

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

[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

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

Isoelectric focusing--polynucleotide/polyacrylamide-gel electrophoresis. A technique to separate and characterize nuclease activities.

Individual native nuclease activities from human leucocytes are separated by using two-dimensional gel electrophoresis in an apparatus that allows the simultaneous running of 28 gels. Proteins are separated by isoelectric focusing in a disc gel, followed by electrophoresis into a slab gel containing DNA. Protein denaturants are avoided in the second dimension by the use of a running pH well above the optimal pH for DNAase (deoxyribonuclease) activity. Electrophoresed gels are incubated in appropriate buffers to activate nuclease activity. After staining for intact DNA, the positions of active enzymes, unobscured by the presence of other proteins, are revealed as colourless spots in a reddish-purple field. The technique is easy to use and is sensitive to 50pg of DNAase I. Versatility is provided by the use of either acidic or basic electrophoresis running buffers and by the use of specific gel incubation conditions to reveal different sets of enzyme activities. Two DNAases active at pH 7.4 in the presence of Mg2+ and Ca2+, and sixteen DNAases active at acidic pH and not requiring metals, are detected. Treatment of the human enzymes with specific glycosidases reveals that many of the human DNAases are glycoproteins containing negatively charged moieties and may be derived from modification of parent activities.

Deoxyribonucleases

Rapid, sensitive and fully automated high-performance liquid chromatographic assay with fluorescence detection for sulmazole and metabolites.

Sulmazole (2-[(2-methoxy-4-methylsulfinyl)phenyl]-3H-imidazo [4,5-b] pyridine; AR-L 115 BS) and two metabolites (sulfide, sulfone) were quantified from directly injected body fluids (plasma, urine, bile) after high-performance liquid chromatographic separation. No internal standard is needed, which is particularly advantageous when fluorescence detection is established. After automated pre-column enrichment on Corasil C18 (37-50 microns), the parent compound and biotransformation products could be backflushed and chromatographed on ODS-Hypersil (5 microns) with a mixture of 0.075 mol/l phosphate buffer-acetonitrile (2:1), an elution rate of 2.0 ml/min and fluorimetric detection (lambda ex = 330 nm; lambda em = 370 nm). A hydroxylated metabolite of sulmazole which occurs preferentially in urine (and bile) can be quantified in the above-mentioned solvent system diluted 1:1 with water, but with different fluorescence characteristics (lambda ex = 345 nm; lambda em = 515 nm). The assay was linear in the range 8-1000 ng/ml. The lower limit of detection was about 8 ng/ml or 80 pg with coefficients of variation between 0.4 and 5.8% for sulmazole.

Animals

Nonlinear pharmacokinetics of the new positive inotropic agent sulmazole in the dog.

Sulmazole (I) 2-[2-methoxy-4-(methylsulfinyl)phenyl]-1H-imidazo[ 4,5-b]pyridine, a new positive inotropic agent, is based on a pyridoimidazole nucleus. Sulmazole pharmacokinetics were monitored in plasma and urine by a specific, sensitive reverse-phase fully automated HPLC system with fluorimetric detection. The hydroxylated metabolite, III, was also monitored in the urine, and unusual pharmacokinetics were observed. Sulmazole disappeared and metabolite II appeared in plasma by zero-order rates for most of their time courses in the 2-15-mg/kg range with a 75% conversion to II. Pure Michaelis-Menten pharmacokinetics were not applicable, and the vmax value increased with increasing dose. Pharmacokinetics of sulmazole and II at 0.7-mg/kg iv doses were characterized by a first-order two-compartment body model. Metabolite III at 0.7- and 2-mg/kg iv doses showed no dose-dependent pharmacokinetics. The unchanged drug and its major metabolite, II, were negligibly excreted renally (0.5-2%). Their renal clearance showed urine flow rate dependencies. The plasma protein bindings were: sulmazole, 40.8 +/- 1.0%; II, 54 +/- 2%; III, 43 +/- 1%, and they were concentration independent.

Animals