[Indications for GnRH analogs in the treatment of genital endometriosis]. / Indications des analogues de la GnRH dans le traitement de l'endométriose génitale.

Three GnRH agonists are currently available in France in clinical medicine with the indication: "Genital or extragenital endometriosis (from stage I to stage IV of the rAFS classification [4] )." The 2004 Cochran meta-analysis showed a significant improvement in the pain score in patients treated with GnRH compared with placebo, with the effect lasting 12 months after cessation of the medication, but few data are available on their advantages in the perioperative situation and in deep endometriosis. A. Audebert found an advantage to preoperative use of GnRHa in severe cases of endometriosis, with a significantly higher rate of patients having surgery that was considered optimal at the end of the intervention, both in terms of the endometriosis lesions and adherences. The benefits of GnRH treatment before medically assisted procreation are, however, supported by the literature.

[Indications of GnRH analogues before and after surgery for endometriosis]. / Indications des analogues de la GnRH en pré- et postchirurgie pour endométriose.

Indications of GnRH analogues before and/or after surgery for endometriosis remain controversial. Although some studies have underlined a decrease in rAFS scores using GnRH analogues pre-operatively, data are insufficient to recommend their systematic use in routine. In the same way, despite an increase in symptom free period subsequent to the use of GnRH analogues post-operatively, no effect of this therapeutic on recurrence rate and fertility outcome has been proved. In addition to a meta-analysis on GnRH analogues in endometriotic women, further studies, especially in women with large endometriomas and with deep pelvic endometriosis, are required to clarify the indications of GnRH analogues associated with surgical management.

[Acceptability of continuous combined versus cyclical HRT: a French multicentric randomized clinical study]. / Acceptabilité par les patientes d'un THS combiné continu versus cyclique: une étude clinique randomisée multicentrique française.

OBJECTIVES: To describe and compare acceptability of treatment and quality of life over 12 cycles in 2 groups of women randomised to continuous combined Climodiène (estradiol valerate 2 mg/dienogest 2 mg) or cyclic Climène (estradiol valerate 2 mg, from D1 to D21/cyproterone acetate 1 mg, from D12 to D21, followed by 7 days off), switching from previous sequential estroprogestative HRT because of side effects. PATIENTS AND METHODS: One hundred forty three postmenopausal women aged 54.39-years were recruited and randomised to Climène (N=68) or Climodiène (N=75). Acceptability was evaluated by the continuation rate in the 2 groups at the end of the 12 cycles study. Assessment of quality of life was obtained from the responses to the women's health questionnaire (WHQ) and to an ad hoc satisfaction questionnaire at baseline, and at the 12th cycle of treatment. RESULTS: No significant difference in baseline characteristics of volunteers were found in the 2 treatment groups except for the socioeconomic status (more town-dwellers in Climène group). Total WHQ score significantly improved after 12 months of treatment with Climène and Climodiène, respectively decreasing from 68.9 to 64.37 (-4.53) and from 69.95 to 62.06 (-7.89), with a trend towards higher improvement with Climodiène, particularly in the hot flushes subscale. In Climodiène group, a significant decrease in sleep problems and cognitive function subscales was found, which is consistent with previous polysomnography and psycho physiological measures data with Climodiène. The evolution of Satisfaction Index is positive and of the same magnitude in the 2 groups, showing an improvement at 12 months: respectively -2.79 (P=0.002) et -2.26 (P=0.02) for Climène and Climodiène. DISCUSSION AND CONCLUSIONS: Even though the benefit/risk ratio of the hormonal substitutive treatment is recognized effective against climateric symptoms which affect the quality of life, this work is the first randomised prospective study on the effects of Climodiène on quality of life in post-menopausal women assessed by the French validated version of the world-wide used WHQ. Decreases in "sleep problems" and "cognitive function" subscales scores in this study are of a magnitude clinically relevant and consistent with previous data on Climodiène impact on postmenopausal symptoms.

[Menopause in 2004: "hormone replacement therapy" is not what it used to be anymore]. / Ménopause en 2004: le "traitement hormonal substitutif" n'est plus ce qu'il était.

PURPOSE: The data concerning post-menopausal hormone replacement therapy (HRT) were recently completely modified. The aim of this review is to present the last studies about post-menopausal HRT and to describe new alternatives to this treatment. CURRENT KNOWLEDGE AND KEY POINTS: In May 2002, the women's health initiative (WHI) trial of post-menopausal HRT was interrupted earlier than expected. The studied hormonal formulation in this arm of the WHI trial was the association of conjugated equine estrogens and medroxyprogesterone. The reason for termination was an increased risk of breast cancer and myocardial infarction in the hormone-therapy group. Later, reports confirmed that this type of HRT could not be used any more for the primary prevention of coronary heart disease even if the absolute risk remained low. There is an increased risk for venous thromboembolism with post-menopausal estroprogestative replacement. This risk does not seem to exist with transdermal estrogens. The other WHI findings concerned the lack of protection against dementia and cognitive decline. On the contrary, osteoporotic hip fractures and colorectal cancers were reduced in the treated group. In April 2004, the estrogen only arm of the same WHI study was also prematurely interrupted because of an increase in the incidence of stroke. The risk of breast cancer was on the contrary not increased after 6.8 years, raising the question of the eventual role of progestins. PERSPECTIVES: The impact of the WHI trial on clinical practice was very important since then. The "Agence Francaise de sécurité sanitaire des produits de santé" (AFSSAPS) edited in May 2004 a public recommendation limiting indication for HRT to patients with severe climacteric symptoms. The treatment must now be prescribed for the shortest time and at the minimal dose. The patient has to be precisely informed about the risks with HRT and the practitioner has to re-evaluate his prescription annually. Hormonal or non-hormonal alternatives have also to be considered as phytoestrogens and tibolone for hot flashes, and raloxifene and diphosphonates for osteoporosis prevention. In any case, a healthy diet, exercise and smoking cessation should be encouraged.

Thiopurine methyl transferase activity: new extraction conditions for high-performance liquid chromatographic assay.

A new liquid-liquid extraction is described for thiopurine methyl transferase (TPMT, EC 2.1.1.67) activity determination: the use of a pH 9.5 NH4Cl buffer solution, before adding the solvent mixture, allows more rapid extraction, avoiding a centrifugation step, and reduces the global cost of analysis. After the extraction step, 6-methylmercaptopurine, synthesised during the enzymatic reaction, is determined by a liquid chromatographic assay. Analytical performance of the assay was tested on spiked erythrocyte lysates. The linear concentration range was 5-250 ng ml(-1) (r> or =0.997, slope=1.497, intercept=-0.367). The recoveries were 82.8, 89.9 and 82.2% for 75, 125 and 225 ng ml(-1), respectively. The coefficients of variation were < or =6.1% for within-day assay (n=6) and < or =9.5% for between-day assay precision (n=6; 14 days). TPMT activity was determined in a French adult Caucasian population (7 =70). The results ranged from 7.8 to 27.8 nmol h(-1) ml(-1) packed red blood cells and the frequency distribution histogram is similar to that previously published.

[Determination of plasma retinol and alpha-tocopherol by HPLC]. / Dosage du rétinol et de l'alpha-tocophérol plasmatique par CLHP.

Retinol (vit A) and alpha-tocopherol (vit E), the active compounds of vitamins A and E, were assayed by reversed-phase high performance liquid chromatography (HPLC) (C18) with UV absorbance detection at 280 nm. Plasma was deproteinized and liquid-liquid extraction performed with hexane. After evaporation, the residue was dissolved in organic solvents (ether:methanol 25:75, V/V). Standard curves were prepared by adding known amounts of standards to plasma. The use of acetonitrile in the mobile phase (acetonitrile:methanol:water 64.5:33:2.5, V/V) avoided interference peaks, giving a total run time of 8 min. Analyte stability required that samples be treated in the dark. Analytical performance was good: recovery around 100%, detection limits 0.015 mg/l for vit A and 0.030 mg/l for vit E, linear range 2 mg/l for vit A and 20 mg/l for vit E, no recorded interference, and between-run and within-run precision with coefficients of variation < 11%. Analytes were stable at room temperature for 24 h (vit A) and 48 h (vit E) in plasma stored in the dark for one month at -20 degrees C. The standard solution containing both vit A and vit E increased vit A stability. Plasma concentrations (mg/l) for vit A and E were respectively: 0.63 +/- 0.17 and 9.61 +/- 3.1 in adults (n = 29), 0.39 +/- 0.17 et 7.10 +/- 2.41 in children 0 to 15 years (n = 21). This method allows regular monitoring of patients with cystic fibrosis to check for retinol and alpha-tocopherol deficiencies. The usefulness and results of the method are discussed in terms of previous studies.

[Evaluation of the change process during treatment of adolescent psychotics]. / Evaluation des processus de changement au cours du traitement d'adolescents psychotiques.

This study rests on work comparing the processes of change in the mental functioning of eleven psychotic teenagers through two perspectives: a psychological perspective centered on the comparison of two psychological examinations carried out at intervals of one and a half and three years; a psychiatric perspective taking into account elements supplied by the doctor and the nursing staff in the facility and concerning the evolution of each patient between the first and second psychological examination. The evolution was judged according to three factors liable to explain the therapeutic effects: the ability of psychic movement through the appearance or the reappearance of a function in the primal process; setting up limits and defenses of a narcissistic order; the improvement in the ability to make bonds. In spite of the difficulties in regrouping the subjects, the comparative results between the tests and the clinical setting generally confirmed our initial hypotheses.