[Postoperative treatment and rehabilitation following flexor tendon injuries]. / Weiterbehandlung und Rehabilitation nach Beugesehnenverletzungen.

BACKGROUND: The ideal surgical and postoperative treatment for flexor tendon injuries, especially in zone 2, is still subject to continuous modifications and professional discussions. OBJECTIVE: Presentation of established rehabilitation concepts, specific problems and new treatment approaches with practical recommendations for application. MATERIAL AND METHODS: Comparison of commonly used treatment concepts by assessing surgical flexor tendon repair, splint choice and clinical application in patients. Discussion of new surgical approaches and standards and their influence on postoperative therapy after flexor tendon injuries. RESULTS: The Washington regimen has retained its status as the standard in the current follow-up treatment of flexor tendon injuries. New suture materials and techniques enable early active rehabilitation of sutured flexor tendons with good clinical results, such as increased range of motion for interphalangeal joint extension and improved distal interphalangeal joint flexion with overall acceptable frequencies of suture rupture. CONCLUSION: A stable tendon repair with smooth gliding is the foundation for treatment after flexor tendon injuries. After intraoperative active digital extension-flexion testing of the sutured tendon an early active rehabilitation approach should follow. New splint designs in combination with primary stable tendon suture techniques have the potential to improve the postoperative outcome, presupposing a reliable cooperation of the patient.

Symptoms, functioning and coping strategies in individuals with schizophrenia spectrum disorders who do not take antipsychotic medication: a comparative interview study.

BACKGROUND: A considerable proportion of people with schizophrenia spectrum disorders do not take antipsychotic medication but seem to be functioning well. However, little is known about this group. To test the assumption that absence of medication is compensated for by more effective coping and increased social support, this study compared symptoms, functioning, coping strategies and social support in non-medicated and medicated individuals with schizophrenia spectrum disorders. METHOD: In all, 48 participants with a DSM-IV schizophrenia spectrum disorder who were taking (n = 25) or not taking antipsychotic medication (n = 23) were included. Assessment consisted of self-ratings of symptoms, symptom-related distress and social support combined with a semi-structured interview that assessed general and social functioning, subjective evaluation of symptoms and coping strategies. RESULTS: Symptom severity and distress did not differ between the groups. However, the non-medicated participants had significantly higher levels of general functioning than medicated participants and a longer duration of being non-medicated was significantly associated with a higher level of general functioning. In contrast to the hypotheses, not taking medication was not associated with more effective coping strategies or with higher levels of social support. Medicated participants more frequently reported the use of professional help as a coping strategy. CONCLUSIONS: Our results corroborate previous studies finding improved functioning in individuals with schizophrenia spectrum disorders who do not take medication compared with those who take medication, but do not support the notion that this difference is explicable by better coping or higher levels of social support. Alternative explanations and avenues for research are discussed.

Impact of Theiler's virus infection on hippocampal neuronal progenitor cells: differential effects in two mouse strains.

AIMS: Disease-associated alterations in hippocampal neurogenesis are discussed as an important factor contributing to long-term consequences of central nervous system diseases. Therefore, the study aimed to determine the impact of Theiler's murine encephalomyelitis virus infection on hippocampal cell proliferation, neuronal progenitor cells and neurogenesis as well as the influence of microglia on respective disease-associated alterations. METHODS: The impact of the infection was evaluated in two mouse strains which differ in the disease course, with an acute polioencephalitis followed by virus elimination in C57BL/6 mice and a chronic demyelinating disease in SJL/J mice. RESULTS: Infection with the low neurovirulent BeAn strain did not exert significant acute effects regardless of the mouse strain. In the chronic phase, the number of neuronal progenitor cells and early postmitotic neurones was significantly reduced in infected SJL/J mice, whereas no long-term alterations were observed in C57BL/6 mice. A contrasting course of microglia activation was observed in the two mouse strains, with an early increase in the number of activated microglia cells in SJL/J mice and a delayed increase in C57BL/6 mice. Quantitative analysis did not confirm a correlation between the number of activated microglia and the number of neuronal progenitor cells and early postmitotic neurones. However, flow cytometric analyses revealed alterations in the functional state of microglial cells which might have affected the generation of neuronal progenitor cells. CONCLUSIONS: Theiler's murine encephalomyelitis virus infection can exert delayed effects on the hippocampal neuronal progenitor population with long-term alterations evident 3 months following infection. These alterations proved to depend on strain susceptibility and might contribute to detrimental consequences of virus encephalitis such as cognitive impairment.

Heartbeat Dynamics Analysis under Cold-Pressure Test using Wavelet p-Leader Non-Gaussian Multiscale Expansions.

Multiscale and multifractal (MF) analyses have been proven an effective tool for the characterisation of heartbeat dynamics in physiological and pathological conditions. However, pre-processing methods for the unevenly sampled heartbeat interval series are known to affect the estimation of MF properties. In this study, we employ a recently proposed method based on wavelet p-leaders MF spectra to estimate MF properties from cardiovascular variability series, which are also pre-processed through an inhomogeneous point-process modelling. Particularly, we exploit a non-Gaussian multiscale expansion to study changes in heartbeat dynamics as a response to a sympathetic elicitation given by the cold-pressor test. By comparing MF estimates from raw heartbeat series and the point-process model, results suggest that the proposed modelling provides features statistically discerning between stress and resting condition at different time scales. These findings contribute to a comprehensive characterization of autonomic nervous system activity on cardiovascular control during cold-pressor elicitation.

Wavelet p-Leader Non-Gaussian Multiscale Expansions for EEG series: an Exploratory Study on Cold-Pressor Test.

Brain dynamics recorded through electroencephalography (EEG) have been proven to be the output of a nonstationary and nonlinear system. Thus, multifractality of EEG series has been exploited as a useful tool for a neurophysiological characterization in health and disease. However, the role of EEG multifractality under peripheral stress is unknown. In this study, we propose to make use of a novel tool, the recently defined non-Gaussian multiscale analysis, to investigate brain dynamics in the range of 4-8Hz following a cold-pressor test versus a resting state. The method builds on the wavelet p-leader multifractal spectrum to quantify different types of departure from Gaussian and linear properties, and is compared here to standard linear descriptive indices. Results suggest that the proposed non-Gaussian multiscale indices were able to detect expected changes over the somatosensory and premotor cortices, over regions different from those detected by linear analyses. They further indicate that preferred responses for the contralateral somatosensory cortex occur at scales 2.5s and 5s. These findings contribute to the characterization of the so-called central autonomic network, linking dynamical changes at a peripheral and a central nervous system levels.

Multiscale properties of instantaneous parasympathetic activity in severe congestive heart failure: A survivor vs non-survivor study.

Multifractal analysis of cardiovascular variability series is an effective tool for the characterization of pathological states associated with congestive heart failure (CHF). Consequently, variations of heartbeat scaling properties have been associated with the dynamical balancing of nonlinear sympathetic/vagal activity. Nevertheless, whether vagal dynamics has multifractal properties yet alone is currently unknown. In this study, we answer this question by conducting multifractal analysis through wavelet leader-based multiscale representations of instantaneous series of vagal activity as estimated from inhomogeneous point process models. Experimental tests were performed on data gathered from 57 CHF patients, aiming to investigate the automatic recognition accuracy in predicting survivor and non-survivor patients after a 4 years follow up. Results clearly indicate that, on both CHF groups, the instantaneous vagal activity displays power-law scaling for a large range of scales, from ≃ 0.5s to ≃ 100s. Using standard SVM algorithms, this information also allows for a prediction of mortality at a single-subject level with an accuracy of 72.72%.

Incidence of sudden cardiac death, myocardial infarction and far- and near-transyears.

We analyzed cycles with periods, tau, in the range of 0.8-2.0 years, characterizing, mostly during 1999-2003, the incidence of sudden cardiac death (SCD), according to the International Classification of Diseases, 10th revision (ICD10), code I46.1. In the tau range examined, only yearly components could be documented in time series from North Carolina, USA; Tbilisi, Georgia; and Hong Kong, in the latter two locations based on relatively short time series. By contrast, in Minnesota, USA, we found only a component with a longer than (= trans) yearly (transyearly) tau of 1.39 years; the 95% confidence interval (CI) of the tau extended from 1.17 to 1.61 years, falling into the category of transyears (defined as a tau and a 95% CI between 1.0 and 2.0 years, with the limits of the 95% CI of the spectral component's tau overlapping neither of these lengths). During the same span from 1999 to 2003 in Arkansas, USA, a component of about 1-year in length was present, and in addition, one with a tau of 1.69 year with a CI extending from 1.29 to 2.07 years, a far-transyear candidate, far-transyears being defined as having a tau with a CI between 1.20 and 2.0 year, with the CI overlapping neither of these lengths. In the Czech Republic, there was also a calendar-yearly tau and one of 1.76 years. In the latter two geographic/geomagnetic areas, the about-yearly and the longer cycles' amplitudes were of similar prominence. The taus are only candidate transyears; the 95% CIs of their taus overlap the 2-year length. When a series on SCD from 1994 to 2003 from the Czech Republic was analyzed, the 95% CI of the transyear's tau no longer overlapped the 2-year length. Transyears were also found in the Czech Republic for myocardial infarctions (MI), meeting the original transyear definition in both a shorter and a longer series. Moreover, in the 1994-2003 series on MI from the Czech Republic, a near-transyear was also found, meeting the definition of a period with a 95% CI overlapping neither precisely 1.0 year nor 1.2 years, along with a far-transyear, defined as a tau between 1.2 and 2.0 years, again with the 95% CI covering neither of these lengths. Herein, we discuss near- and far-transyears more generally in the light of their background in physics and the concept of reciprocal cyclicities.

Chronomics, neuroendocrine feedsidewards and the recording and consulting of nowcasts--forecasts of geomagnetics.

A multi-center four-hourly sampling of many tissues for 7 days (00:00 on April 5-20:00 to April 11, 2004), on rats standardized for 1 month in two rooms on antiphasic lighting regimens happened to start on the day after the second extremum of a moderate double magnetic storm gauged by the planetary geomagnetic Kp index (which at each extremum reached 6.3 international [arbitrary] units) and by an equatorial index Dst falling to -112 and -81 nT, respectively, the latter on the first day of the sampling. Neuroendocrine chronomes (specifically circadian time structures) differed during magnetically affected and quiet days. The circadian melatonin rhythm had a lower MESOR and lower circadian amplitude and tended to advance in acrophase, while the MESOR and amplitude of the hypothalamic circadian melatonin rhythm were higher during the days with the storm. The circadian parameters of circulating corticosterone were more labile during the days including the storm than during the last three quiet days. Feedsidewards within the pineal-hypothalamic-adrenocortical network constitute a mechanism underlying physiological and probably also pathological associations of the brain and heart with magnetic storms. Investigators in many fields can gain from at least recording calendar dates in any publication so that freely available information on geomagnetic, solar and other physical environmental activity can be looked up. In planning studies and before starting, one may gain from consulting forecasts and the highly reliable nowcasts, respectively.

Point-process high-resolution representations of heartbeat dynamics for multiscale analysis: A CHF survivor prediction study.

Multiscale analysis of human heartbeat dynamics has been proved effective in characterizeing cardiovascular control physiology in health and disease. However, estimation of multiscale properties can be affected by the interpolation procedure used to preprocess the unevenly sampled R-R intervals derived from the ECG. To this extent, in this study we propose the estimation of wavelet coefficients and wavelet leaders on the output of inhomogeneous point process models of heartbeat dynamics. The RR interval series is modeled using probability density functions (pdfs) characterizing and predicting the time until the next heartbeat event occurs, as a linear function of the past history. Multiscale analysis is then applied to the pdfs' instantaneous first order moment. The proposed approach is tested on experimental data gathered from 57 congestive heart failure (CHF) patients by evaluating the recognition accuracy in predicting survivor and non-survivor patients, and by comparing performances from the informative point-process based interpolation and non-informative spline-based interpolation. Results demonstrate that multiscale analysis of point-process high-resolution representations achieves the highest prediction accuracy of 65.45%, proving our method as a promising tool to assess risk prediction in CHF patients.

P-leader multifractal analysis and sparse SVM for intrapartum fetal acidosis detection.

Interpretation and analysis of intrapartum fetal heart rate, enabling early detection of fetal acidosis, remains a challenging signal processing task. Among the many strategies that were used to tackle this problem, scale-invariance and multifractal analysis stand out. Recently, a new and promising variant of multifractal analysis, based on p-leaders, has been proposed. In this contribution, we use sparse support vector machines applied to p-leader multifractal features with a double aim: Assessment of the features actually contributing to classification; Assessment of the contribution of non linear features (as opposed to linear ones) to classification performance. We observe and interpret that the classification rate improves when small values of the tunable parameter p are used.

Characterization of leucine zipper complexes by electrospray ionization mass spectrometry.

The development of "soft" ionization methods has enabled the mass spectrometric analysis of higher-order structural features of proteins. We have applied electrospray ionization mass spectrometry (ESI-MS) to the analysis of the number and composition of polypeptide chains in homomeric and heteromeric leucine zippers. In comparison with other methods that have been used to analyze leucine zippers, such as analytical ultracentrifugation, gel chromatography, or electrophoretic band shift assays, ESI-MS is very fast and highly sensitive and provides a straightforward way to distinguish between homomeric and heteromeric coiled-coil structures. ESI-MS analyses were carried out on the parallel dimeric leucine zipper domain GCN4-p1 of the yeast transcription factor GCN4 and on three synthetic peptides with the sequences Ac-EYEALEKKLAAX1EAKX2QALEKKLEALEHG-amide: peptide LZ (X1, X2 = Leu), peptide LZ(12A) (X1 = Ala, X2 = Leu), and peptide LZ(16N) (X1 = Leu, X2 = Asn). Equilibrium ultracentrifugation analysis showed that LZ forms a trimeric coiled coil and this could be confirmed unequivocally by ESI-MS as could the dimeric nature of GCN4-p1. The formation of heteromeric two- and three-stranded leucine zippers composed of chains from LZ and LZ(12A), or from GCN4-p1 and LZ, was demonstrated by ESI-MS and confirmed by fluorescence quenching experiments on fluorescein-labeled peptides. The results illustrate the adaptability and flexibility of the leucine zipper motif, properties that could be useful to the design of specific protein assemblies by way of coiled-coil domains.

Kinetics and biotransformation of lormetazepam. II. Radioimmunologic determinations in plasma and urine of young and elderly subjects: first-pass effect.

A specific and sensitive radioimmunoassay has been developed for a new benzodiazepine, lormetazepam. After intravenous injection, lormetazepam levels in plasma fell in three (alpha, beta, gamma) dispositional phases, two of them (alpha, beta) mainly reflecting different distribution processes. The terminal (gamma) phase correlated well with the rate of renal elimination of glucuronides. Oral doses were completely absorbed with widely varying absorption half-lifes (t1/2s) amounting to an average of 0.67 +/- 0.53 hr. Dose-dependent maximum plasma levels were reached in about 2 hr. Lormetazepam undergoes first-pass metabolism of about 20% of an oral dose. Total clearance was in the range of 200 ml/min. There was a trend toward slower terminal disposition phase in elderly subjects. In younger subjects, the terminal phase t1/2 was about 10 hr. Lormetazepam glucuronide peak plasma levels were reached by about 6 hr. Thereafter, the level fell in one (elimination) phase, with a t1/2 of 12 hr in young subjects and with a significantly (p < 0.05) different t1/2 of about 20 hr in the elderly. Renal clearance was calculated as about 30 to 40 ml and did not show an age-dependent difference. Recovery of lormetazepam glucuronide with urine amounted to 70% to 80% of the dose during 72 hr after intravenous injection in both age groups.

Protein A antibody-capture ELISA (PACE): an ELISA format to avoid denaturation of surface-adsorbed antigens.

Adsorption to a polymeric surface may severely alter the antigenic structure of proteins through unfolding. A conventional capture ELISA in which a protein antigen is adsorbed to the microtiter plate may be unsuitable for testing the specificity of antibodies directed against native proteins (C. Schwab and H.R. Bosshard (1992) J. Immunol. Methods 147, 125). This problem can be overcome by PACE, a new ELISA procedure in which monoclonal or polyclonal antibodies are first allowed to equilibrate with biotinylated antigen in solution. Thereafter, the antigen-antibody complex (and free antibody) is bound to the microtiter plate through protein A. Captured antigen-antibody complex is detected by streptavidin-alkaline phosphatase and p-nitrophenylphosphate. A competition assay is accomplished by co-incubation of biotinylated and non-biotinylated antigens before capture to the protein A-coated plate. PACE combines the advantages of a solution-phase immunoassay (Farr assay) with the ease of a solid-phase ELISA. PACE has been used to test the conformational specificity of polyclonal and monoclonal antibodies against native and denatured cytochrome c, and of a polyclonal antiserum against a coiled coil leucine zipper peptide. Since a biotin group can be attached specifically to the N-terminal residue of synthetic peptides, PACE is also useful for assaying reactivity against peptide antigens which are difficult to adsorb to microtiter plates.

Differences and similarities among circadian characteristics of plasma renin activity in healthy young women in Japan and the United States.

A circadian rhythm of plasma activity (PRA) was demonstrated for both Japanese and North American women, the latter mostly Caucasians of mixed ethnic origin. The results were based on blood samples withdrawn at 4-hour intervals during a 24-hour span (in March 1978) from 20 subjects from Fukuoka (average age 20.4 +/- 0.1 years) and 16 subjects from Minneapolis (average age 20.2 +/- 0.4 years). The rhythms in the two populations showed similarities in some characteristics and differences in others. The timing of high values, i.e., of acrophases, objectively assessed by curve-fitting (and of corresponding 95 per cent confidence limits) was at 07(36) (05(00), 10(16) and 06(32) (03(00), 10(00) for Japan and USA, respectively. As objective measures of the extent of predictable rhythmic change mean amplitudes, in nanograms per milliliter per hour (ng/ml/hour), were similar (0.31 and 0.32); a statistically significant difference (P less than 0.05) was found in mean amplitudes expressed as percentage of the rhythm-adjusted average. Mean rhythm-adjusted average values (mesors) were lower in women from Japan than in those from the United States: (1.64 +/- 0.14 and 2.39 +/- 0.23 ng/ml/hour, respectively; P less than 0.01). A statistically significant difference in dietary salt, indicated by differences between the Japanese and North American women in the urinary excretion of sodium and chloride (P less than 0.05), almost certainly contributed to these results.

Diflucortolone valerate (Nerisona): a comparative vasoconstriction test in artificially induced hyperemia of the skin.

In 20 healthy volunteers of both sexes the vasoconstrictive activity of diflucortolone valerate in two of its commercially available formulations (water-in-oil emulsion and pure fat base) was compared with that of four other substances: fluocinonide; betamethasone-17,21-dipropionate; hydrocortisone-17-butyrate; and clobetasol-17-propionate in corresponding galenical formulations. The visual assessment of vasoconstrictive activity after 10 hours revealed a statistically significant superiority of diflucortolone valerate in its fat base over the corresponding galenical formulations of fluocinonide, clobetasol-17-propionate, and hydrocortisone-17-butyrate. Diflucortolone valerate in a water-in-oil emulsion was statistically better after eight hours than the cream formulations of fluocinonide; clobetasol-17-propionate, and betamethasone-17,21-dipropionate.

Thermographic analysis of skin test reaction using AGA thermovision.

The course of infrared thermography including isothermograms on the skin surface was investigated considering blood flow, redness of the skin and permeability of blood vessel, in the following skin reactions: 1. Intracutaneous injection of histamine and histamine liberator compound 48/80 increased the heat radiation. Local application of antihistamine externa which decreased the development of the urticarial histamine reaction, increased the infrared radiation of the skin surface. Combined injection of histamine or histamine liberators with antihistamines in a sufficient dosis (1:1 respectively 4:1) diminished also the heat radiation in addition to the urticarial reaction. 2. The Pyrexal reaction of the skin with early erythema and later papule development shows an equivalent picture in the AGA Thermovision. The pretreatment shows an equivalent picture in the AGA Thermovision. The pretreatment of the skin with corticosteroid ointments shows a corresponding lowering of the erythema, of papule development as well as of heat radiation. The blanching of corticosteroids after occlusive dressing is difficult to recognize by the isotherms of AGA Thermovision. 3. Allergic reactions of the immediate type show, corresponding to the wheal eruption, a marked increased of heat radiation combined with a projection of the enlarged veins on the skin surface. 4. Allergic reactions of the delayed type are combined with a definite elevation of heat radiation of the skin. The area of a positive skin test with allergic eczematous reaction shows a distinct elevation of ann infrared radiation. Although the allergic skin area which was substantiated by a positive skin test was no longer visible, a distinct infrared radiation could be detected. Preventive treatment of the test area of skin patch-testing with corticosteroids inhibits the heat radiation even if the allergic eczematous reaction occurs faintly. The thermographic analysis of the different skin test reactions complied with the morphological aspects of the reaction.

Investigations of pharmacokinetics of ethinyloestradiol to specific consideration of a possible first-pass effect in women.

Ethinyloestradiol-3H was given intravenously and orally to four and three women, respectively, in a dose of 60 micrograms and 3 mg. To another three female volunteers, 100 micrograms of ethinyloestradiol was administered by both routes in succession. Drug concentration in plasma and total radioactivity in plasma, urine and faeces were measured for different periods of time. Intraindividual comparison of the area under the drug level vs. time curve after intravenous and oral administration of 100 micrograms showed that ethinyloestradiol is subject to an about 60% first-pass effect in women. The time course of ethinyloestradiol concentration in plasma can be described by a 3-compartment model after intravenous injection and by a 2-compartment model after oral administration, because an early disposition phase with a half-life of about 15 minutes only becomes visible after i.v. injection. On an average, the terminal half-life of unchanged ethinyloestradiol level and total radioactivity was calculated to be about 1 day. However, a high variability was found with this parameter as well as with the rate and degree of elimination in urine.

PIP: Investigations of pharmacokinetics of ethinyl estradiol (EE) to specific consideration of a possible 1st-pass effect in women are reported. Tritiated EE was given intravenously and orally to 4 and 3 women, respectively, in a dose of 60 mcg and 3 mg. 3 female volunteers received 100 mcg of EE by both routes in succession. EE concentration in plasma and total radioactivity in plasma, urine, and feces were measured for different periods of time. Intraindividual comparison of the area under the drug level vs time curve following iv and oral administration of 100 mcg showed that EE is subject to about 60% 1st-pass effect in women. The time course of EE concentration in plasma can be described by a 3-compartment model after iv injection and by a 2-compartment model after oral administration, because an early disposition phase with a 1/2-life of about 15 only became visible after iv injection. The terminal 1/2-life of unchanged EE level and total radioactivity was calculated to be about 1 day.

Investigations of pharmacokinetics of levonorgestrel to specific consideration of a possible first-pass effect in women.

PIP: This investigation, using levonorgestrel, estimated the extent of a first-pass effect and established a pharmacokinetic model to describe drug concentrations after intravenous and oral administration. 3 women received 30 mcg of levonorgestrel in succession by intravenous and oral routes; another 6 were given 150 mcg (as Microgynon) in similar fashion. Radiolabeled levonorgestrel was used for intravenous administration of 30 mcg and oral administration for 150 mcg. Radioimmunoassay was used to determine plasma drug level after all treatments. Urine and feces eliminations were also recorded. After intravenous and oral administration, drug concentration and total plasma radioactivity declined in 2 disposition phases, with half-lives in the range of 1.5 hours/day. After intravenous administration, an early phase with a half-life of about 10 minutes was observed. Levonorgestrel was rapidly absorbed, with a half-life of about 20 minutes. Orally administered doses were completely absorbed. Intraindividual comparison showed that intravenous and oral administration of levonorgestrel is not subject to any first-pass effect.^ieng

Bio-availability and pharmacokinetics of cyproterone acetate-14C and ethinyloestradiol-3H after oral administration as a coated tablet (SH B 209 AB).

PIP: Bioavailability and pharmacokinetics of carbon-14-cyproterone acetate-methylene (2 mg) and tritiated ethinyl estradiol (50 mg) after oral administration as a coated tablet (SH B 209 AB) were investigated. 8 women received the compounds, and carbon-14 and tritium activity in plasma, urine, and feces was determined up to 7 or 10 days postadministration. Cyproterone acetate was completely absorbed. The maximum plasma level was reached in 30 minutes to 3 hours, when 2.2% of the dose was found in total plasma corresponding to 24 ng eq/ml. The plasma level decreased with a 1/2-life of 7.9 hours (distribution and elimination) and later with a 1/2-life of 2.5 days (elimination). Elimination via urine was 37% and up to Day 10 postadministration 91% of the dose was found in urine and feces. Ethinyl estradiol was adsorbed very rapidly and almost completely with the maximum plasma level reached in 60 minutes. At this time 10% of the dose was found in the plasma corresponding to 2.1 ng eq/ml. The plasma level dropped up to about 8 hours postadministration with a 1/2-life of 5.1 hours and later with a 1/2-life of 27 hours. Ethinyl estradiol was eliminated in urine and feces in the ratio of 4:6 and 91% of the dose was recovered.^ieng

Development and application of a radioimmunoassay of the new progestagen gestodene.

A radioimmunoassay for the determination of gestodene (17-ethinyl-13-ethyl-17 beta-hydroxy-4,15-gonadien-3-one) in human plasma is described with regard to procedure, specificity, accuracy and reproducibility. Antiserum was raised against gestodene-3-O-(carboxymethyl)oxime-BSA in rabbits and [9,11-3H]-gestodene tracer was used with a specific radioactivity of 2.16 TBq/mmol. The final antiserum dilution was 1: 200,000. RIA was performed according to routine methods using diethylether plasma extracts and the charcoal separation technique. Cross-reactivity of antiserum with cortisol, 17 beta-estradiol, progesterone, testosterone and ethinylestradiol was less than 0.03%; levonorgestrel exhibited a 5% cross-reactivity. No cross-reactivity with metabolites of gestodene or ethinylestradiol was found. Accuracy and precision of the assay were tested using human plasma samples spiked with 1, 5 and 10 ng/ml gestodene. Accuracy was within 94 to 104% of the nominal values. Within-assay and between-assay coefficients of variation were in the range of 4.7-6.5% and 10.3-13.1%, resp. This RIA was used to follow plasma gestodene levels after single oral administration of 75 micrograms of gestodene combined with 30 micrograms ethinylestradiol as tablet and coated tablet in a cross-over design in 6 female test subjects. Plasma gestodene levels were equivalent after both treatments.