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Biomedical subjects

R Wyss

Publications and source records attributed to R Wyss.

At least 73 records · Page 4Linked to original sources
PubMed1990

Determination of the monoamine oxidase B inhibitor Ro 19-6327 in plasma by high-performance liquid chromatography using precolumn derivatization with fluorescamine and fluorescence detection.

A specific high-performance liquid chromatographic (HPLC) method using precolumn derivatization and fluorescence detection was developed for the determination of the monoamine oxidase B inhibitor Ro 19-6327 in human plasma. After extraction of the basified plasma with tert.-butyl methyl ether-1-butanol (8:2, v/v) and back-extraction into dilute phosphoric acid, the solution was neutralized with phosphate buffer and the drug derivatized with fluorescamine. The derivative was chromatographed on a reversed-phase C8 column, using phosphate buffer-acetonitrile (68:32, v/v) as mobile phase, and fluorescence detection (excitation 370 nm, emission 485 nm). The limit of quantification was 1 ng/ml using 1 ml of plasma. The recovery was 79% in the range 5-200 ng/ml and the inter-assay precision was 3.1-7.9% in the range 2-500 ng/ml. The compound proved to be stable in human plasma. Moderate instability was found in rat plasma and, surprisingly, severe instability in dog plasma. Measures for handling unstable dog plasma samples are described. An HPLC method with UV detection was used for the analysis of dog and rat plasma samples, which is also described briefly. The fluorescence method, which was five times more sensitive than the UV method, was successfully applied to a human tolerance study.

Chromatography, High Pressure Liquid↗
PubMed1990

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. I. Contraceptive efficacy and side effects. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

A multicentre clinical trial, including 19 centres in 13 countries, assessed the contraceptive efficacy and clinical acceptability of a Silastic 382 vaginal ring releasing 20 micrograms of levonorgestrel for at least 90 days. A total of 1005 women entered the study and 8176.74 woman-months of experience was gathered. The rate of intrauterine pregnancy at one year of use was 3.6 per 100 women (95% confidence interval 2.2-5.0), and of ectopic pregnancy, 0.2% (one case). The principal reasons for discontinuation were menstrual disturbances (17.2% at one year), vaginal symptoms (6.0%) and repeated expulsion of the ring (7.1%). The pregnancy rate with this 20 micrograms levonorgestrel-releasing vaginal ring compares favourably with that of a low estrogen combination oral contraceptive tested by WHO and is less than half that of a progestogen-only oral contraceptive in a WHO randomized study. It is concluded that the WHO intravaginal ring releasing an average of 20 micrograms of levonorgestrel per 24 hours is an effective method of contraception for at least one year of use.

Administration, Intravaginal↗
PubMed1990

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. II. Expulsions and removals. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

This paper investigates the relationship between expulsions and removals, and demographic characteristics of 1005 women from 19 centres using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. Emphasis is placed on discontinuations of method use due to expulsions, on the number and rate of expulsions, and the time at which the first expulsion occurred. The overall life-table discontinuation rate due to expulsion was 7.1% at one year. Life-table discontinuation rates increased with parity and were highest in Asian and lowest in European women. In respect to the number of expulsions experienced by women (expulsions did not necessarily lead to discontinuation), the women of high parity and those from Asia and Europe have the highest rates. The life-table first expulsion rate is 29% at one year. Such rates are highest in Chinese and Asian women. Following a first expulsion, the second expulsion rate is 45% by the end of the subsequent six months. The majority of first expulsions occur at defaecation (134 or 57% of 234 women), urination (12%) and during menstruation (17%). Rings were removed by 121 (12%) women on 201 occasions and for a variety of reasons. The main medical reasons were vaginal discharge and irritation, bleeding pain and dyspareunia. Others removed the ring during defaecation, intercourse or because the ring came out of place. Women also removed rings for curiosity, to show their husbands and to clean.

Administration, Intravaginal↗
PubMed1990

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. III. The relationship between pregnancy rate and body weight. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

This paper investigates the relationship between pregnancy rates and body weight of 1005 women using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. While the overall pregnancy rate at one year was 3.7%, it was found that women have an increasing risk of pregnancy with increasing body weight. For example, a woman of 40 kg has an estimated pregnancy rate of 1.7% in contrast to 9.8% for a woman of 80 kg weight.

Administration, Intravaginal↗
PubMed1990

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. IV. Bleeding patterns. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

A multicentred clinical trial was conducted in 12 countries to assess the contraceptive efficacy and side effects of a low-dose levonorgestrel-releasing vaginal ring. Contraceptive efficacy and side effects, expulsions and removals, and the relation between pregnancy rate and admission body weight of the women have been reported previously. The effect of ring use on vaginal bleeding patterns as observed from daily menstrual diaries kept by the women is the object of this paper. A total of 1005 women were fitted with the ring and 702 of them provided a menstrual diary suitable for analysis. The description of the bleeding patterns is made using a 90-day reference period approach and following the guidelines published by WHO. In addition the longest bleeding/spotting episode and longest bleeding/spotting-free interval are calculated over the entire diary length. Half of the ring users have vaginal bleeding patterns similar to normal untreated patterns. A quarter experience irregular bleeding, 10% have prolonged cycles and 10% have shortened cycles. Over one year of continuous use, there appears to be no significant trend in these patterns. Users with the worst bleeding patterns tend to discontinue first during the clinical trial and are influenced by their more recent experience of vaginal bleeding irregularities. Life-table analysis of discontinuation rates gives an underestimation of the true incidence of bleeding irregularities. Some comments are made on the limitations of the methods of analysis of menstrual diaries.

Clinical Trials as Topic↗
PubMed1990

Malaria prophylaxis and self-therapy in airline crews.

The risk of malaria infection in airline crews is estimated to be 0.5 per 1,000 persons per night in areas with high levels of malaria transmission. Routine chemoprophylaxis for years is not recommended because of possible side effects. Airline crews should therefore use appropriate measures to prevent mosquito bites. In addition, they may need to carry "standby" medication with them to be used for presumptive treatment of a febrile illness if medical attention is not readily available.

Aerospace Medicine↗
PubMed1988

Determination of highly protein bound drugs in plasma using high-performance liquid chromatography and column switching, exemplified by the retinoids.

During method development for the determination of either isotretinoin, tretinoin and their 4-oxo-metabolites, or etretinate, acitretin and 13-cis-acitretin in plasma using high-performance liquid chromatography and column switching, recovery problems arose, when undiluted plasma samples were injected directly onto the precolumn. These recovery problems may be due to the strong binding of the retinoids to different plasma proteins. Measures to overcome this strong protein binding, such as variation of the injection solution composition and the purge mobile phase, were systematically investigated. Best recoveries were obtained by diluting of plasma with 9 mM sodium hydroxide-acetonitrile (8:2, v/v) and protein precipitation with ethanol for the isotretinoin and etretinate series, respectively, in combination with the use of a purge mobile phase containing ammonium acetate and 10-20% acetonitrile. Less effective was the use of a longer precolumn or heating of the precolumn.

Blood Proteins↗
PubMed1988

Quantitative analysis of retinoids in biological fluids by high-performance liquid chromatography using column switching. II. Simultaneous determination of etretinate, acitretin and 13-cis-acitretin in plasma.

An automated gradient high-performance liquid chromatographic method for the determination of etretinate, acitretin and 13-cis-acitretin in plasma was developed, using a column-switching technique. After protein precipitation with ethanol, 0.5 ml of the supernatant was injected onto a precolumn (17 mm x 4.6 mm I.D.), filled with 37-53 microns C18 Corasil. Polar plasma components were washed out using 1% ammonium acetate and 1% acetic acid-acetonitrile (8:2, v/v); the retained retinoids were then transferred to the analytical column (125 mm x 4 mm I.D., filled with 5-microns ODS material) in the backflush mode, separated by gradient elution and detected at 360 nm by UV detection. The limit of quantification was 2 ng/ml and the inter-assay precision in the concentration range 20-1000 ng/ml was between 0.9 and 4.0% for all three compounds. To optimize the recovery for etretinate (greater than 60%), protein was precipitated from plasma with ethanol before injection, instead of direct injection of plasma samples, and a mobile phase containing 20% acetonitrile, instead of pure water or buffer, was used.

Acitretin↗
PubMed1988

Determination of cefetamet and its orally active ester, cefetamet pivoxyl, in biological fluids by high-performance liquid chromatography.

Two different, simple and rapid high-performance liquid chromatographic methods with ultraviolet detection, using a common sample work-up procedure, were developed for the determination of cefetamet, an in vitro active cephalosporin, and its orally absorbed pivaloyloxymethyl ester, cefetamet pivoxyl. After protein precipitation with perchloric acid, plasma samples were analysed on C18 reversed-phase columns with 4 mM perchloric acid-acetonitrile (83:17, v/v) and 0.1 M phosphate buffer (pH 6.5)-acetonitrile (60:40, v/v) as mobile phases for the determination of cefetamet and cefetamet pivoxyl, respectively. Urine samples were diluted with water and analysed in the same manner, using 4 mM perchloric acid-acetonitrile (85:15, v/v). The limits of quantification were 0.2, 0.5 and 20 micrograms/ml for the determination of cefetamet and cefetamet pivoxyl in plasma and cefetamet in urine, respectively. The intra-assay precision was less than or equal to 1.5% for cefetamet and less than or equal to 2.3% for cefetamet pivoxyl. The inter-assay precision for cefetamet was less than or equal to 2.4%. Cefetamet was stable in human plasma when stored at -20 degrees C for three months or at 22 degrees C for 24 h. For the determination of cefetamet pivoxyl, which was extremely unstable in plasma (greater than 70% degradation in 1 h), samples were drawn into vacutainers containing citric acid and immediately added to sodium fluoride. The method for cefetamet was successfully applied to several thousand plasma and urine samples from humans, dogs and rats. No unchanged drug could be detected in human or dog plasma after the administration of cefetamet pivoxyl.

Ceftizoxime↗
PubMed1988

Quantitative analysis of retinoids in biological fluids by high-performance liquid chromatography using column switching. I. Determination of isotretinoin and tretinoin and their 4-oxo metabolites in plasma.

A fully automated gradient high-performance liquid chromatographic method for the determination of isotretinoin, tretinoin and their 4-oxo metabolites in plasma was developed, using the column-switching technique. After dilution with an internal standard solution containing 20% acetonitrile, 0.5 ml of the sample was injected onto a precolumn (17 X 4.6 mm I.D.), filled with C18 Corasil 37-53 micron. Proteins and polar plasma components were washed out using 1% ammonium acetate-acetonitrile (9:1, v/v) as mobile phase 1. After valve switching, the retained components were transferred to the analytical column in the backflush mode, separated by gradient elution and detected at 360 nm by UV detection. Using two coupled reversed-phase columns (125 mm long), the separation of cis and trans isomers was possible, and all four compounds could be quantified down to 2 ng/ml of plasma. The inter-assay precision in the concentration range 20-100 ng/ml was between 1.0 and 4.7% for all compounds.

Animals↗
PubMed1988

Continuous synthesis of two protein-kinase-C-related proteins after down-regulation by phorbol esters.

The phorbol 12-myristate 13-acetate (PMA)-dependent down-regulation of immunoprecipitable protein kinase C was studied in human breast cancer cell lines that display different growth inhibitions toward the tumor promoter. PMA induces translocation of [35S]methionine-prelabeled cytosolic protein kinase C to membranes, followed by complete degradation of the enzyme (t1/2, 2 hr). PMA does not affect the protein kinase C synthesis; 20-80% of total protein kinase C of control cells was still immunoprecipitable as membrane-bound 74- and 80-kDa protein kinase C-related polypeptides if cells were allowed to incorporate [35S]methionine during PMA exposure for greater than 6 hr. These two proteins lack protein kinase activity and phorbol ester binding but reveal V8 peptide patterns identical to the active forms of protein kinase C (77/80 kDa) of PMA-untreated cells. The amounts of the immunoprecipitable membrane-bound 80-kDa protein kinase C-related polypeptide synthesized during the prolonged PMA treatment appear to inversely correlate with the extent of PMA-mediated growth inhibition of the respective human breast cancer cell line. These data suggest that after homologous down-regulation, functional protein kinase C (77/80 kDa) is replaced by a population of membrane-associated but enzymatically inactive protein kinase C-related polypeptides (74/80 kDa).

Breast Neoplasms↗
PubMed1988

Pharmacokinetics of cefetamet (Ro 15-8074) and cefetamet pivoxil (Ro 15-8075) after intravenous and oral doses in humans.

This report summarizes the results of three pharmacokinetic studies of cefetamet and cefetamet pivoxil conducted in normal adult male volunteers. In the first study the pharmacokinetics of cefetamet were evaluated after intravenous infusion of doses ranging from 133 to 2,650 mg. Over this dose range, the pharmacokinetics were linear. A dose-proportional increase in the area under the curve from zero to infinity was observed, whereas total clearance (140.3 +/- 23.6 ml/min), renal clearance (130.3 +/- 18.2 ml/min), volume of distribution at steady state (0.288 +/- 0.023 liter/kg), fraction excreted unchanged in the urine (94 +/- 11%), and elimination half-life (2.07 +/- 0.18 h) were independent of dose. In a second study the absolute bioavailability of single 1,500-mg doses of a tablet formulation of the pivaloyloxymethylester of cefetamet was evaluated under conditions of fasting and after a standard breakfast. Administration with food increased the extent of absorption (from 31 +/- 7 to 44 +/- 4%) while decreasing the rate of absorption (time to maximum concentration of drug in plasma increased from 3.0 +/- 0.6 to 4.8 +/- 0.4 h). The third study consisted of multiple oral administration of 1,000 mg of a similar oral tablet formulation twice daily for 10 days. This regimen was preceded and followed by intravenous administration of a 500-mg bolus dose of cefetamet. Oral doses were administered with breakfast and dinner. The absolute bioavailability of the tablet formulation was assessed after the first dose and after both the morning and the evening doses on day 10 of oral therapy. The compound was consistently absorbed to the extent of approximately 50% with no significant differences observed between the morning and evening doses on day 10.

Administration, Oral↗
PubMed1987

Immunological quantitation of phospholipid/Ca2+-dependent protein kinase of human mammary carcinoma cells: inverse relationship to estrogen receptors.

The amounts of phospholipid- and Ca2+-dependent protein kinase (PKC) of various human mammary tumor cells containing (ER+) or lacking (ER-) estrogen receptors were estimated by quantitative immunoblotting. According to several criteria the polyclonal anti-PKC antibody raised in rabbits against porcine brain PKC specifically recognizes an 80-kDa polypeptide on immunoblots. This 80-kDa PKC presumably represents the autophosphorylated form of the holoenzyme. Immunological quantitation of PKC revealed that the levels of immunodetectable PKC varied widely among the various human mammary carcinoma cell lines but closely matched the amounts determined by enzyme activity and phorbol ester binding in the respective cell line. The largest amounts of immunodetectable PKC were found in the ER- human mammary tumor cells (0.5 to 1.5 micrograms PKC/mg of cytosolic protein). These data indicate that ER- human mammary carcinoma cell lines express significantly higher levels of PKC than their estrogen-receptor-containing counterparts.

Breast Neoplasms↗