PubMed Health⌕ Search

Biomedical subjects

P Wüthrich

Publications and source records attributed to P Wüthrich.

At least 19 recordsLinked to original sources
PubMed2006

Drug/lactose co-micronization by jet milling to improve aerosolization properties of a powder for inhalation.

The aim of this work was to formulate a powder for inhalation with fusafungine, a drug substance initially highly cohesive. The classical approach based on micronization by jet milling to prepare respirable drug particles and then blending with a carrier was first applied. A fractional factorial experimental design was implemented to screen six formulation parameters. The effect of drug/lactose co-micronization on aerosolization was then evaluated. In vitro deposition studies were performed with the twin stage glass impinger and the inhaler Spinhaler. Micronization did not induce DSC-detectable amorphization and gave a highly cohesive, poor flowable powder with a theoretical aerodynamic diameter of 5 microm. The powder was then blended with coarse lactose and optionally fine lactose. Unfortunately, the respirable fraction could not be optimized and remained below 10%. On the other hand, a co-micronized powder drug/fine lactose 50:50 gave a respirable fraction of 16%. Following blending with a carrier, the respirable fraction and the emitted dose fraction reached 23% and 69%, respectively. The use of a fine lactose grade for co-micronization was essential. In conclusion, this study demonstrated that co-micronization with a fine lactose is an efficient and simple strategy to formulate a powder for inhalation with enhanced aerosolization properties, especially for highly cohesive drug substance.

Administration, Inhalation↗
PubMed1998

[Post-mortem evaluation following oncologic treatment of the functional and bacteriologic status of 25 permanent venous access devices].

Permanent venous access devices allow long-term parenteral treatment under relatively safe and comfortable conditions. Nevertheless, this use is associated with some degree of (particularly infectious) morbidity. 25 permanent access devices were removed surgically in immediate autopsies and cultured. Some half were infected, with a clear prevalence (40%) for Staphylococcus coagulase negative. The results were related to clinical history and compared with the figures and conclusions of other studies. It is proposed that in certain situations cultures of native blood should be carried out more frequently through the permanent venous access, with a view to possible specific targeted antibiotic therapy associated with the heparinized lock.

Adult↗
PubMed1996

[Effect of postoperative retransfusion of autologous blood products on hemostasis in heart surgery].

In cardiac surgery a reduction of homologous blood products is mainly achieved by autologous blood salvage. Unprocessed retransfusion of autologous blood may induce changes in hemostasis. We assessed changes of activated clotting times (ACT) after retransfusion of unprocessed (1) oxygenator blood and (2) shed mediastinal blood. In 41 patients undergoing cardiac surgery (37 revascularization and 4 valve procedures) with a mean cardiopulmonary bypass time of 116.3 min, ACT was measured at the following time points: pre- and postoperatively, and before and after retransfusion of oxygenator blood and shed mediastinal blood. A significant prolongation of ACT values was only seen between pre- to postoperative blood (p < 0.003). Retransfusion of oxygenator blood changed ACT from 120 +/- 25 vs 116 +/- 17 sec and retransfusion of shed mediastinal blood showed a mean ACT of 118 +/- 14 vs 115 +/- 20 sec from before to after transfusion. There was a significant correlation between the ACT value in the unprocessed oxygenator blood and the ACT value measured in the patient after retransfusion (r = 0.41, p < 0.02). 6 patients receiving over 1 litre of unprocessed autologous blood (either from the oxygenator or the mediastinum) in less than 60 minutes showed a significant increase of ACT value after transfusion (p < 0.05). Hence, under normal conditions, retransfusion of unprocessed autologous blood will not significantly alter hemostasis measured by the ACT test in patients undergoing cardiac surgery.

Adult↗
PubMed1996

Radioimmunoassay of Antarelix, a luteinizing hormone releasing-hormone antagonist, in plasma and its application for pharmacokinetic study in dogs.

A procedure for the radioimmunoassay (RIA) of Antarelix (teverelix) in plasma has been developed for the pharmacokinetic study of this potent LHRH antagonist in dogs. Antiserum was produced by coupling the deamidated Antarelix analog to bovine serum albumin by a carbodiimide reaction and immunizing rabbits with the conjugate. The crossreactivity of the antiserum with LHRH, LHRH agonist Metereline and LHRH antagonists tested was negligible, except for Antide which displayed a crossreactivity of 33%. No crossreactivity with Antarelix metabolites could be detected. The RIA is suitable for the direct determination of Antarelix in plasma, with a minimum detectable level of 1.12 fmol/assay. The accuracy and precision of the method were assessed with plasma samples spiked with Antarelix at concentrations ranging from 0.4 to 6.4 pmol/ml. The recovery was 104.8% with intra- and interassay CV between 1 and 3.7%. Pharmacokinetic profiles of Antarelix in dogs were established following an i.v. or a s.c. dose of 10 micrograms/kg.

Animals↗
PubMed1994

Growth hormone-releasing activity of hexarelin in humans. A dose-response study.

Hexarelin is a new hexapeptide (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) that stimulates the release of growth hormone both in vitro and in vivo. In this double-blind, placebo-controlled, rising-dose study we evaluated the growth hormone releasing activity of hexarelin in healthy human subjects. Twelve adult male volunteers received single intravenous boluses of 0.5, 1 and 2.micrograms.kg-1 hexarelin as well as placebo. For safety, drug doses were given in a rising-dose fashion with placebo randomly inserted into the sequence. Plasma growth hormone concentrations increased dose-dependently after the injection of the peptide, peaking at about 30 min and then decreasing to baseline values within 240 min with a half-life of about 55 min. The mean peak plasma growth hormone concentrations (Cmax) were 3.9, 26.9, 52.3, 55.0 ng.ml-1 after 0, 0.5, 1 and 2 micrograms.kg-1, respectively. The corresponding areas under the curve of growth hormone plasma levels from drug injection to 180 min (AUC0-180) were 0.135, 1.412, 2.918 and 3.695 micrograms.min.ml-1. The theoretical maximum response (Emax) and the dose that produces half of the maximum response (ED50) were estimated using logistic regression. The calculated ED50 values were 0.50 and 0.64 microgram.kg-1 for Cmax and AUC0-180, respectively. The corresponding Emaxs were 55.1 ng.ml-1 and 3936 ng.min.ml-1, thus indicating that the effect after the 2 micrograms.kg-1 dose is very close to the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effect of formulation additives upon the intranasal bioavailability of a peptide drug: tetracosactide (ACTH1-24).

Nasal absorption of tetracosactide (ACTH1-24; Synacthen) was evaluated in anesthetized rats and compared to intravenous and intramuscular (i.m.) administration. The effect of formulation additives on tetracosactide bioavailability was studied following modification of nasal saline solution. Poloxamer 407 (Pluronic F-127) was used as a vehicle for drug sustained release, whereas sodium glycocholate and bacitracin were used as enhancers. Tetracosactide plasma levels were monitored with radioimmunoassay. Nasal bioavailability was low (4.4%) compared to i.m. (24%). Poloxamer 407 addition did not improve drug kinetics profiles and showed a non-significant decrease in bioavailability (4%). On the other hand, both enhancers effectively increased tetracosactide nasal absorption. The sodium glycocholate effect was very fast (Tmax = 5 min), but did not last long. Moreover, absorption was increased threefold compared to the simple formulation. On the other hand, maximum tetracosactide levels in plasma were reached after 15 min for the formulation containing bacitracin as enhancer, and tetracosactide bioavailability was strongly increased, to 24%, i.e., as much as after an i.m. injection.

Absorption↗
PubMed1993

Antarelix (EP 24332) a novel water soluble LHRH antagonist.

A novel water soluble LHRH antagonist (EP 24332-Antarelix) is described. Its activity in vitro and in vivo in several animal models is given. Antarelix (Ac-D-Nal, D-Cpa, D-Pal, Ser, Tyr, D-Hci, Leu, Lys-(iPr), Pro, D-Ala-NH2) in view of its potency, modest histamine-liberating activity and high water solubility has been selected for further development.

Animals↗
PubMed1989

[The transnasal route of drug administration. Aspects of nasal anatomy and physiology].

The use of transnasal administration of drugs has gained interest with the synthesis of new polypeptidic biologically active substances. Since few years an increasing number of therapeutical hormones delivered through the nose are now available to treat disorders that only used to require parenteral injections to be effective. In its first part the present review describes the anatomy and physiology of the nose in order to gain insight in this site of delivery. The second part deals more specifically with models used to study transnasal absorption and describes parameters that modify drug absorption in relation with the model chosen.

Administration, Intranasal↗
PubMed1984

[Statistics of obligatory accident insurance--a contribution to health statistics in Switzerland].

After our compulsory accident insurance was reorganized, all employees and workers of Switzerland have been insured against accidents and occupational diseases since the beginning of 1984. The federal law on accident insurance prescribes also homogeneous statistics and SUVA has to run this task. The data thus gained are important for the Swiss health statistics and make it possible to set forth on a broader basis the work begun by SUVA under the previous law. The essay reviews object, organization and use of the data as well as the various aspects of data protection.

Accidents, Occupational↗
PubMed1981

[Analysis of the structure and conditions in the cause of occupational accidents].

A random sample of 11,162 events was drawn from 225,275 accidents which were certified by the Swiss National Accident Insurance Fund, in order to assess the structural characteristics of accidents during work and their relation to a number of variables. Domicile, sex and occupation of the accident victim, activity prior to the accident, the course of the accident and its severity were studied. Forestry and the building trade exhibit high relative risks of 2.6 and 2.3, respectively. The dangers specific to separate occupations are identified. The complex relationships are examined more closely by means of log-linear models in multivariate analyses. It is found that structural variables in this model like domicile and sex do not only determine the type of occupation of the accident victim but influence the course and severity of the accident, i.e. the duration of work incapacity.

Accidents, Occupational↗
PubMed1981

[Nutrition behavior, eating habits and mass index of 4 Swiss cities].

As part of the Swiss National Research Program for the Prevention of Cardiovascular Disease, body weight and length of the participants were recorded and eating habits were assessed by the 24-h-recall method and dietary history. The body mass index was found to increase with age, pointing to excessive energy intake. The lower the socioeconomic group, the higher the index. Men eat more meat and meat products but less fruit than women, and drink more alcohol. In the French-speaking part of Switzerland, significantly more cheese and more alcohol, but less meat, brown bread and milk are consumed than in the German-speaking part. The consumption of edible fats and fat-containing food differs as between the two parts of the country. In certain age groups, a low positive correlation is observed between total plasma cholesterol and fat ingestion, and a low inverse correlation between total cholesterol and milk consumption and frequency of meals.

Adolescent↗
PubMed1979

[Drinking behavior in Switzerland].

The results of a broad survey of drinking behaviour in Switzerland are reported. It is based on a questionnaire considered to be representative obtained from 1500 residents of Switzerland between 15 and 74 years of age. The study confirms previous findings that, similar as in other countries, alcohol consumption in Switzerland is distributed in the population as a logarithmic curve. The results demonstrate that the alcohol consumed in amounts which are considered to be dangerous to health (daily consumption of pure alcohol: 80 grams and more) was found to be 30% of total consumption in German and French Switzerland, and 47% in Italian Switzerland respectively. In contrast to other countries there is no predominance of particular beverages, but there are some clear-cut preferences for certain beverages in certain areas within the country. The study further demonstrates that in areas with higher average consumption a higher percentage of heavy consumers is found; this is particularly the case for French and Italian Switzerland. Moreover, a higher average consumption is associated with an increase in mortality rates from alcohol-related cirrhosis of the liver. The relationship between regional average consumption and mortality rates from cirrhosis indicates not a linear, but an exponential increase of the latter with rising consumption. It was found that the following social-demographic variables are significantly associated with the prevalence to drinking: sex, age, income and education.

Adolescent↗
PubMed1977

Social problems of alcoholics.

A comparison of abstainers and alcoholics showed that the latter were more often involved in social conflicts and breaches of social norms. The breaches of social values were as important as the drinking in society's definition of an alcoholic.

Aggression↗