Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases.

Background: This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases. Patients and methods: Pre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N = 521) and postmenopausal women untreated for ABC (PALOMA-2; N = 666) were randomized 2 : 1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression-free survival (PFS), safety, and patient-reported quality of life (QoL) were evaluated by prior treatment and visceral involvement. Results: Visceral metastases incidence was higher in patients with prior resistance to ET (58.3%, PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In patients with prior resistance to ET and visceral metastases, median PFS (mPFS) was 9.2 months with palbociclib plus fulvestrant versus 3.4 months with placebo plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35-0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In patients with nonvisceral metastases, mPFS was 16.6 versus 7.3 months, HR 0.53; 95% CI 0.36-0.77. In patients with visceral disease and naive to ET in the advanced disease setting, mPFS was 19.3 months with palbociclib plus letrozole versus 12.9 months with placebo plus letrozole (HR 0.63; 95% CI 0.47-0.85); ORR was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not reached with palbociclib plus letrozole versus 16.8 months with placebo plus letrozole (HR 0.50; 95% CI 0.36-0.70). In patients with prior resistance to ET with visceral metastases, palbociclib plus fulvestrant significantly delayed deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported QoL was maintained with palbociclib plus letrozole in patients naive to endocrine-based therapy for ABC. Conclusions: Palbociclib plus ET prolonged mPFS in patients with visceral metastases, increased ORRs, and in patients previously treated for ABC, delayed QoL deterioration, presenting a standard treatment option among patients with visceral metastases amenable to endocrine-based therapy. Clinical trial registration: NCT01942135, NCT01740427.

Papaverine as a replacement for pentoxifylline to select thawed testicular or epididymal spermatozoa before ICSI.

OBJECTIVES: Pentoxifylline has been used to improve sperm motility in Assisted Reproductive Technology mainly by initiating sperm motility in immotile spermatozoa samples obtained surgically. Indeed, as Intracytoplasmic Sperm Injection leads to very poor results when using immotile gametes, pentoxifylline gives better results by easing the selection of viable sperm mobilized after incubation. In 2011, the French Haute Autorité de santé decided that pentoxifylline used for in vivo purpose proposed Insufficient Medical Service and pentoxifylline was thus withdrawn from the French materia medica. We here assessed the efficacy on spermatozoa motility and the safety of papaverine, another phosphodiesterase inhibitor, for the replacement of pentoxifylline. METHODS: Sixteen frozen-thawed epididymal or testicular samples displaying no or very poor spontaneous motility (≤5% total motility) were subjected to both pentoxifylline (3.6mM) and papaverine (93µM). A duplicate Mouse Embryo Assay and an In Vitro Fertilization Mouse Assay in duplo were used to discard any toxic effect of papaverine. RESULTS: Papaverine gave better results than pentoxifylline (mean total motility: 27% vs 23%, P<0.05). No Effect Level were observed in the two different Mouse Embryo Assays performed. CONCLUSION: Papaverine is a useful tool to replace pentoxifylline in ICSI programs to select viable spermatozoa in frozen-thawed sperm samples displaying no or very poor motility.

Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies.

STUDY QUESTION: Can independent predictors of pregnancy-associated plasma protein-A (PAPP-A) levels be identified in a group of women who conceived following IVF/ICSI? SUMMARY ANSWER: The significantly decreased PAPP-A level in IVF and ICSI pregnancies compared with non-IVF/ICSI pregnancies was correlated strongly with the serum estradiol (E2) level at ovulation triggering. WHAT IS KNOWN ALREADY: The first trimester prenatal combined screening test for fetal aneuploidies in pregnancies conceived following assisted reproduction techniques (ART) is complicated by an alteration of the maternal biomarkers free ß-hCG and PAPP-A, causing a higher false-positive rate compared with pregnancies which are conceived naturally. The use of controlled ovarian stimulation prior to IVF/ICSI is suggested to be the principle reason for these alterations of biomarkers in ART pregnancies. STUDY DESIGN, SIZE, DURATION: Between January 2010 and December 2011, 1474 women who conceived naturally and 374 women who conceived following IVF (n = 89), ICSI (n = 204) or intrauterine insemination (IUI, n = 81) were included in this retrospective study. Only singleton pregnancies were eligible for this study. For all women, serum analysis was performed in the same clinical laboratory. Measurement of nuchal translucency (NT) thickness was performed by four physicians belonging to the same infertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: First-trimester combined screening test of aneuploidy parameters (maternal age, PAPP-A and free ß-hCG, NT thickness) were compared between non-ART and ART (IVF, ICSI and IUI) singleton pregnancies. Next, a minimal threshold E2 level at ovulation triggering was suggested for IVF/ICSI pregnancies above which the PAPP-A levels were significantly decreased compared with non-ART pregnancies. Finally, a multivariate analysis was performed to reveal independent predictors of PAPP-A level in IVF/ICSI pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: We showed a decrease of the multiple of the median (MoM) PAPP-A level in IVF and ICSI singleton pregnancies compared with non-ART singleton pregnancies (P < 0.001), with MoM values of 0.74 (0.16-3.16) and 0.81 (0.12-4.61) versus 0.98 (0.14-5.76), respectively. Analysis of variance of the overall model was highly significant (Fisher test 3.76, P = 0.01), indicating that the model explains a significant portion of the variation in the data. No difference in PAPP-A level was found between non-ART and IUI pregnancies. The free ß-hCG level and NT thickness did not differ between ART and non-ART pregnancies. PAPP-A levels in IVF and ICSI pregnancies were strongly correlated with the E2 level at ovulation triggering. We showed by multivariate analysis that an E2 cut-off level of 1300 pg/ml at the time of ovulation could predict a significantly lower PAPP-A level at first trimester combined screening (ß -0.239 ± 0.088, P < 0.005). LIMITATION, REASONS FOR CAUTION: The measures of biochemical markers can differ between laboratories and with the used equipment; therefore, extrapolation of the E2 cut-off level to other infertility centres should be undertaken with caution. WIDER IMPLICATIONS OF THE FINDINGS: One should be careful when using correction factors for ART patients undergoing the first trimester combined screening test. The proposed E2 cut-off level may help to identify a subgroup of women within the population of ART patients for whom use of a correction factor is justified. STUDY FUNDING/COMPETING INTEREST(S): None.

Linear plasmon dispersion in single-wall carbon nanotubes and the collective excitation spectrum of graphene.

We have measured a strictly linear pi plasmon dispersion along the axis of individualized single-wall carbon nanotubes, which is completely different from plasmon dispersions of graphite or bundled single-wall carbon nanotubes. Comparative ab initio studies on graphene-based systems allow us to reproduce the different dispersions. This suggests that individualized nanotubes provide viable experimental access to collective electronic excitations of graphene, and it validates the use of graphene to understand electronic excitations of carbon nanotubes. In particular, the calculations reveal that local field effects cause a mixing of electronic transitions, including the "Dirac cone," resulting in the observed linear dispersion.

Anomalous angular dependence of the dynamic structure factor near Bragg reflections: graphite.

The electron energy-loss function of graphite is studied for momentum transfers q beyond the first Brillouin zone. We find that near Bragg reflections the spectra can change drastically for very small variations in q. The effect is investigated by means of first principle calculations in the random phase approximation and confirmed by inelastic x-ray scattering measurements of the dynamic structure factor S(q, omega). We demonstrate that this effect is governed by crystal local field effects and the stacking of graphite. It is traced back to a strong coupling between excitations at small and large momentum transfers.

Relationship between even early cleavage and day 2 embryo score and assessment of their predictive value for pregnancy.

The aim of this study was, firstly, to define the different patterns of early cleavage (EC) observed at 26 h after either IVF or intracytoplasmic sperm injection (ICSI) and, secondly, to assess the predictive value of one of these patterns, even EC (EEC), on pregnancy rate in combination with day 2 embryo score. In the first part of the study, the relationship between three different EC patterns (EEC, uneven EC and EC with fragmentation of the day 2 embryo) and embryo morphology was determined. EEC was shown to be strongly associated with good embryo morphology. In the second part of the study, it was shown that EEC used in combination with embryo score improved selection of embryos for transfer. The presence of EEC significantly (P < 0.001) enhanced mean implantation rate in all transfer categories involving identically scored embryos, in both compulsory single embryo transfers and elective single embryo transfers. Multivariate analysis demonstrated that EEC and embryo score had strong complementary predictive value for pregnancy. Based on these findings, it was concluded that even though they are associated, EEC and embryo score could be combined to increase pregnancy rate, especially in elective single embryo transfer programmes.

Early cleavage: an additional predictor of high implantation rate following elective single embryo transfer.

The value of early cleavage (EC) assessment is still being debated. The aim of this prospective study was to examine the predictive value of EC assessment performed exactly 26 h after insemination by IVF or intracytoplasmic sperm injection (ICSI) in a programme of elective single embryo transfer (SET) performed at day 2. If day 2 scoring demonstrated several embryos with high implantation potential, an EC embryo was transferred preferentially. EC was assessed only during normal laboratory hours so that there were two groups: EC assessed, and EC not assessed, the latter being the control. A total of 277 elective SET were performed in women under 37 years undergoing their first IVF or ICSI cycle (mean age 30.5 years, range 21-37). The overall clinical and ongoing pregnancy rates were 40.1% (111/277) and 32.9% (91/277) respectively. Significantly higher overall clinical and ongoing pregnancy rates were obtained after transfer of an EC embryo than a non-EC embryo: 49.4 versus 33.3% (P < 0.05) and 42.4 versus 25.9% (P < 0.02) respectively. However there was no significant difference between the EC assessed and control groups: 40.4 versus 39.3% and 33.2 versus 32.1 respectively. These findings confirm the value of EC assessment for selection of embryos with high implantation potential.

[How to improve ART results? Is France behind other countries? Strategy for single embryo transfer: The value of embryo selection and embryo freezing]. / Comment améliorer nos résultats en AMP? La France est-elle en retard? Stratégie de transfert de l'embryon unique: la place du choix de l'embryon et de la congélation embryonnaire.

Multiple embryo transfer is associated with a high frequency of twin pregnancies with costly complications involving both mother and child. As a result high priority is currently being given to the development of single embryo transfer (SET) programs. France seems to be lagging behind Northern European countries in the development of SET and widespread use of SET will depend on convincing physicians that this policy will not have a negative impact on success rate, as has been the case for many protocols described in the literature as well as in our own experience. Our SET program includes patients less than 36 years of age undergoing their first FIV-ICSI. If two embryos showing satisfactory morphology are obtained, one is selected transferred and the other is systematically frozen. Selection for transfer is based on two criteria, i.e. observation of even early cleavage 26 hours after FIV-ICSI and evaluation of embryo morphology score on day 2. Embryo morphology score is based on the presence of four blastomeres and absence of blastomere irregularities and anucleated fragmentation. Last, a prerequisite for SET is an effective freezing program. A pregnancy rate of 13% per thawing was sufficient enough to obtain a cumulative pregnancy rate after SET (N = 205) and subsequent frozen embryo transfer (FET) similar to the cumulative pregnancy rate obtained after double embryo transfer (N = 394) and subsequent FET (46.3 vs 46.7%, NS). Twin delivery rate were respectively 2,6% after SET and 26,6% after double embryo transfer (P < 0.01).

[Elective single embryo transfer: a justified policy for selected patients]. / Transfert électif d'un seul embryon: une option justifiée pour une population de patientes sélectionnées.

OBJECTIVE: Prevention of twin pregnancies using elective Single Embryo Transfer (e-SET) is now considered by many Assisted Reproductive Techniques teams as a necessity. The aim of this study was to assess the efficacy of e-SET in a prospective manner in a selective population of patients using Take Home Baby Rate per couple as principal parameter. PATIENTS AND METHODS: This prospective study was conducted from January 2003 to December 2004. Elective Single Embryo was proposed to women above 37 years in their first IVF or ICSI attempt. It was then performed only in cases when at least one embryo with high implantation potential (score-4 embryo in our embryo scoring) was obtained for transfer and one more (score-3 or score-4 embryo) was available for freezing. RESULTS: e-SET was proposed and accepted in 225 couples (25% of eligible couples and 7.8% of total population) and was possible in 96 of these). Two embryos were transferred in all other eligible patients (Double Embryo Transfer group=DET). Cumulative delivery rate after fresh embryo transfers and, if necessary, after frozen-thawed embryo transfers were 39.5% per couple e-SET group and 41.7% in DET group (NS). On the other hand, the percentage of twin pregnancies was significantly different between the two groups (2.6% vs 26.6% respectively; P<0.01). DISCUSSION AND CONCLUSION: In women younger than 37 years in their first IVF/ICSI attempt, the elective transfer of only one embryo with high implantation potential strongly allowed to avoid twin pregnancies without any significant delivery rate decrease. This transfer policy is particularly efficient in laboratories displaying good results in their embryo freezing program.

Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: final results of a double-blind, placebo-controlled phase III trial.

BACKGROUND: Cancer patients receiving chemotherapy experience thromboembolic complications associated with the use of long-term indwelling central venous catheters (CVCs). This prospective, double-blind, placebo-controlled, multicenter study evaluated whether prophylactic treatment with a low molecular weight heparin could prevent clinically relevant catheter-related thrombosis. PATIENTS AND METHODS: Patients with cancer undergoing chemotherapy for at least 12 weeks (n=439) were randomly assigned, in a 2:1 ratio, to receive either dalteparin (5000 IU) or placebo, by subcutaneous injection, once daily for 16 weeks. Patients underwent upper extremity evaluation with either venography or ultrasound at the time of a suspected catheter-related complication (CRC) or upon completion of study medication. The primary end point, as determined by a blinded adjudication committee, was the occurrence of a CRC, defined as the first occurrence of any one of the following: clinically relevant catheter-related thrombosis that was symptomatic or that required anticoagulant or fibrinolytic therapy; catheter-related clinically relevant pulmonary embolism; or catheter obstruction requiring catheter removal. RESULTS: There was no significant difference in the frequency of CRCs between the dalteparin arm (3.7%) and the placebo arm (3.4%; P=0.88), corresponding to a relative risk of 1.0883 (95% confidence interval 0.37-3.19). No difference in the time to CRC was observed between the two arms (P=0.83). There was no significant difference between the dalteparin and placebo groups in terms of major bleeding (1 versus 0) or overall safety. CONCLUSIONS: Dalteparin prophylaxis did not reduce the frequency of thromboembolic complications after CVC implantation in cancer patients. Dalteparin was demonstrated to be safe over 16 weeks of treatment in these patients.

Crude cumulative delivery rate following ICSI using intentionally frozen-thawed testicular spermatozoa in 51 men with non-obstructive azoospermia.

This prospective study evaluated the crude cumulative delivery rate following delayed intracytoplasmic sperm injection (ICSI) using spermatozoa recovered by testicular extraction (TESE) and intentionally frozen in men with non-obstructive azoospermia (NOA). This procedure can be termed 'cryoTESE-ICSI'. This study involved a series of 118 patients who underwent testicular biopsy for diagnosis of NOA in the period from January 1998 to December 2002. Testicular histology confirmed the diagnosis of NOA. Testicular parenchyma was obtained surgically from both testicles under general anaesthesia. Cryopreservation of spermatozoa was performed in 51 of 118 patients (43%). Ninety-nine delayed ICSI procedures were performed. Frozen-thawed suspensions were used in all cycles. Application of pentoxifylline was required to stimulate spermatozoa in 52% of cases. Fertilization, embryo transfer, and ongoing pregnancy rates were 60, 98 and 29% respectively. The crude cumulative delivery rate was 49% after two cycles and 57% after four cycles. A total of 39 healthy children were born in 29 deliveries. Thus, cryoTESE-ICSI is an effective procedure for routine use in patients with NOA. The main advantages of cryoTESE-ICSI are to (i) avoid repeated surgical biopsy, (ii) ensure the availability of spermatozoa when the ovarian stimulation cycle is begun, and (iii) allow programmed biopsy and therefore dissociate it from ICSI.

Outcome of ICSI in HIV-1-infected women.

BACKGROUND: Since 2001, French law has permitted the use of assisted reproductive technology in human immunodeficiency virus (HIV)-1 infected women under strict conditions. This report describes a preliminary series of seropositive women who underwent assisted reproduction treatment at our facility. To minimize contamination of culture media, equipment, and therefore of male gametes and embryos, we chose to perform ICSI in all cases. The outcome of ICSI was compared with the outcome in an age-matched group of non-HIV-1-infected women. Since several previous reports have indicated that HIV infection may be associated with a decrease in spontaneous fertility, our goal was also to assess the fertility status of the HIV-1-infected women entering our ICSI programme. METHODS: The French law governing the use of assisted reproduction protocols in HIV-1-infected women was strictly applied. The inclusion criteria were absence of ongoing disease, CD4((+)) count >200 cells/mm(3), and stable HIV-1 RNA level. Since mean age at the time of ICSI was higher in HIV-1-infected women than in the overall group of non-HIV-infected women, we compared outcome data in HIV-1-infected women (group I) to a group of non-HIV-1-infected women matched with regard to age and follicle retrieval period (group II) as well as to the overall group of women who underwent ICSI at our institution (group III). RESULTS: A total of 66 ovarian stimulations was performed in 29 HIV-1-infected-infected women. The percentage of cancelled cycles was higher in infected women than in matched controls (15.2 versus 4.9%, P < 0.05). The duration of ovarian stimulation (13.3 versus 11.7 days, P < 0.05) and amount of recombinant FSH injected (2898 versus 2429 IU, P < 0.001) were also higher in infected women. The number of retrieved oocytes, mature oocytes, and embryos obtained as well as embryo quality was similar in all groups. The fertilization rate was higher in infected women than in matched controls (67 versus 60%, P < 0.01). The pregnancy rate was not significantly different between groups I and II (16.1 versus 19.6%) in spite of the fact that the number of embryos transferred was purposefully restricted in the HIV-1-infected group to minimize multiple pregnancy (2.0 versus 2.4, not significant). CONCLUSION: The results of this preliminary series of ICSI cycles in HIV-1-infected women indicate that optimal ovarian stimulation is slightly more difficult to achieve than in matched seronegative women. However, when criteria for oocyte retrieval were fulfilled, ICSI results were similar to those of age-matched controls.

[GnRH antagonists and embryo implantation potential]. / Antagonistes de la GnRH et potentiel implantatoire embryonnaire.

In several trials, the GnRH antagonists regimens have been associated with a slightly lower pregnancy and implantation rate than the established GnRH agonist protocols. Several embryo classification systems have been developed to grade embryo quality, and a cumulative embryo score has been proposed to predict pregnancy. The cumulative embryo score is based on a 4-point embryo score in which all cleaved embryos were assigned 1 point and 1 additional point was added for each of the following features: absence of fragmentation (or fragmentation involving <20% of the embryonic surface), absence of irregularities in blastomere size or shape, and four-cell stage (regardless of cell morphology). This cumulative embryo score is highly correlated with embryo implantation rates. In a non prospective study concerning 641 IVF cycles with oocyte retrieval, pregnancy and implantation rates were statistically lower in the group of patients treated with GnRH antagonist. The explanation of this difference is the indication in IVF cycles: the women with tubal infertility and/or endometriosis had lower pregnancy and implantation rates in IVF cycles if an antagonist was administrated. There was no difference between the 2 groups in ICSI cycles. Subsequently, in IVF cycles, antagonist should not be administrated to women with tubal infertility and/or endometriosis.

Embryo score is a better predictor of pregnancy than the number of transferred embryos or female age.

OBJECTIVE: To compare the value of 17 IVF variables, including a new mean score of transferred embryos (MSTE), in predicting pregnancy rate. DESIGN: Retrospective study. SETTING: Private IVF unit. PATIENT(S): Women who underwent 10,000 embryo transfers. MAIN OUTCOME MEASURE(S): Duration of infertility, type of infertility, female age, rank of IVF attempt, type of ovarian treatment, progesterone level, sperm count, sperm motility, sperm morphology, number of retrieved oocytes, number of mature oocytes, maturation rate, number of embryos obtained, fertilization rate, number of transferred embryos, cumulative embryo score (CES), mean score of transferred embryos (MSTE), and pregnancy rate. RESULT(S): Outcome of IVF-ET was significantly correlated with female age, type of infertility, number of retrieved oocytes, number of mature oocytes, maturation rate, embryos obtained, fertilization rate, transferred embryos, CES, and MSTE. Multivariate analysis demonstrated that MSTE was a better predictor of pregnancy than the number of transferred embryos and female age. CONCLUSION(S): Embryo quality is the best predictor of pregnancy. The embryo score described herein should be used in IVF-ET programs to choose the best embryos for transfer.

Pentoxifylline initiates motility in spontaneously immotile epididymal and testicular spermatozoa and allows normal fertilization, pregnancy, and birth after intracytoplasmic sperm injection.

PURPOSE: Pentoxifylline (PF) has been used to enhance sperm motility in many in vitro fertilization programs. The twofold purpose of this study was to determine whether PF stimulates fresh or frozen epididymal and testicular totally immotile spermatozoa and whether it can be used to select viable spermatozoa for intracytoplasmic sperm injection (ICSI). METHODS: To test the effect of PF on motility, 10 samples of totally immotile spermatozoa were incubated for 10 min with 3.6 mM PF. Motility was initiated in all cases (14.8% mean motility after PF treatment of five samples of fresh or frozen epididymal spermatozoa and 13.6% mean motility of five samples of fresh or frozen testicular spermatozoa). To assess PF for selection of viable spermatozoa before ICSI, we compared the outcome of ICSI in 20 cycles using fresh or frozen epididymal or testicular PF-treated immotile spermatozoa and 139 control ICSI using fresh or frozen epididymal or testicular spontaneously motile spermatozoa. RESULTS: Fertilization rates were similar in the PF and control groups (45.2% vs. 51.0%). Embryo quality and division stages at the time of transfer were comparable. Six pregnancies occurred in PF-ICSI group (30.0% per cycle vs. 26.6% in control group) including two deliveries of healthy children and four ongoing pregnancies.

Somatic mutation in the neonatal mouse.

Several mechanisms that diversify the adult immune repertoire, such as terminal deoxynucleotidyl transferase-dependent N region addition, are not available to the neonatal mouse. One important process that contributes to protective immunity in the adult is somatic mutation, which plays a major role in the generation of high affinity memory B cells. It is not clear whether B cells in the neonatal mouse can activate the somatic mutation machinery. To investigate this, we immunized neonates with poly(L-Tyr,L-Glu)-poly-D,L-Ala-poly-L-Lys complexed with methylated BSA, or (4-hydroxy-3-nitrophenyl)acetyl coupled to chicken gamma-globulin. Eight to fourteen days after priming, V(D)J rearrangements of known V(H) genes (V(H)SM7 family) were screened for mutations using a temperature-melt hybridization assay and oligonucleotide probes specific for complementarity-determining regions I and II; possible mutations were confirmed by sequence analysis. More mutations per sequence were found in heavy chains from neonates immunized with (4-hydroxy-3-nitrophenyl)acetyl coupled to chicken gamma-globulin than in those from neonates immunized with poly(L-Tyr,L-Glu)-poly-D,L-Ala-poly-L-Lys complexed with methylated BSA. Mutations were found in heavy chains lacking N regions, suggesting that B cells of the putative fetal lineage can somatically mutate and diversify an initially limited repertoire. Since neonates immunized as early as 1 or 2 days after birth had mutations, the somatic mutation machinery can be activated soon after birth, suggesting that early vaccination should result in affinity maturation and protective immunity in the neonate.

Two recent developments in XMCD.

This paper reports on two new technical developments concerning sample environments for X-ray magnetic circular dichroism (XMCD). The first measurements under high pressures of up to 30 GPa are described. The difficulties of combining the techniques of high pressure and XMCD are commented on. The second development involves the use of a fast-switching magnetic field. A new superconducting device is used to perform XMCD measurements on paramagnetic compounds in magnetic fields of up to 6 T. The small amplitude of the XMCD signal imposes, for a given signal-to-noise ratio, a noise less than a few 10(-5). The signal-to-noise ratio is improved by the use of a series of acquisitions, switching the magnetic field between each acquisition. A very fast switching mechanism has been built based on mechanical rotation of a superconducting coil, with the sample kept in place inside the coil. The XMCD signals at the L(II,III)-edges of paramagnetic rare-earth compounds have been measured at 4.5 K in fields of up to 6 T with a switching time of 11 s.