Prospective, randomized, comparative study of leuprorelin + human menopausal gonadotropins versus ganirelix + recombinant follicle-stimulating hormone in oocyte donors and pregnancy rates among the corresponding recipients.

AIM: To compare the clinical pregnancy rate in recipients of oocytes from donors treated with leuprorelin + human menopausal gonadotropins (hMG) with that obtained when the donors were treated with ganirelix + recombinant follicle-stimulating hormone (rFSH). The secondary aim was to compare the donors' response to the two treatments. METHOD: A prospective, randomized, comparative study was conducted between January 2005 and November 2006 in a private hospital. Donors were randomized to receive a long protocol of leuprorelin + hMG (group DI) or ganirelix + rFSH (group DII). Their respective recipients were randomized to group RI or group RII, respectively. RESULTS: The characteristics of the donors were similar in both groups. More cycles were cancelled in group DI than in group DII (28.1% vs. 2.5%; p < 0.05). Compared with donors in group DII, the donors in group DI required a significantly higher dose of gonadotropins (2794 +/- 957 U vs. 1777 +/- 1043 U; p < 0.05) and more days of stimulation (11.7 +/- 2.3 vs. 9.5 +/- 1.5; p < 0.05); they also yielded fewer oocytes (15.0 +/- 6.1 vs. 17.9 +/- 8.6; p < 0.05). There were no differences in the characteristics of the recipients, in the fertilization rate or in the number of embryos transferred. The quality of transferred embryos was better in group RI (8.0 +/- 1.2 vs. 7.5 +/- 1.6; p < 0.05), and this group also achieved a better pregnancy rate per embryo transfer than did group RII (62.3% vs. 48.4%; p < 0.05). CONCLUSIONS: Treating oocyte donors with leuprorelin + hMG produces among recipients a greater probability of clinical pregnancy per embryo transfer than when donors are treated with ganirelix + rFSH; however, more cycles are cancelled and the former treatment is more unpleasant for donors.     

Brain response to complex visual stimuli in Parkinson's patients with hallucinations: A functional magnetic resonance imaging study

Visual hallucinations (VH) in Parkinson's disease (PD) have been associated with gray matter reductions in visual associative areas and with abnormal patterns of brain activation in posterior and frontal regions. However, all previous fMRI studies have used simple visual stimuli. The objective of our study was, therefore, to compare the pattern of brain activation during a one‐back face detection task. We examined 10 PD patients with VH, 10 PD patients without VH, and 10 controls matched for age and education. The fMRI task consisted in three blocks of 21‐face stimuli (activation condition) and three blocks of 21‐colored mosaics (control condition). Subjects were asked to press a key when two identical stimuli were presented consecutively. During the face condition, compared with patients without VH, hallucinating PD patients showed significant reductions in the activation of several right prefrontal areas, such as the inferior (BA 10,47), superior (BA 6/8), middle frontal (BA 8), and anterior cingulate gyrus (BA 31/32). In the control condition, we found a hyperactivation in the hallucinating PD sample compared with the nonVH patients in the right inferior frontal gyrus. A dysfunction of the frontal areas associated with the control of attention could predispose to VH through an abnormal processing of relevant and irrelevant visual stimuli. © 2008 Movement Disorder Society     

Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index

Introduction

Recurrence risk in breast cancer varies throughout the follow-up time. We examined if these changes are related to the level of expression of the proliferation pathway and intrinsic subtypes.

Methods

Expression of estrogen and progesterone receptor, Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK 5/6) was performed on tissue-microarrays constructed from a large and uniformly managed series of early breast cancer patients (N = 1,249). Subtype definitions by four biomarkers were as follows: luminal A (ER + and/or PR+, HER2-, Ki-67 <14), luminal B (ER + and/or PR+, HER2-, Ki-67 ≥14), HER2-enriched (any ER, any PR, HER2+, any Ki-67), triple-negative (ER-, PR-, HER2-, any Ki-67). Subtype definitions by six biomarkers were as follows: luminal A (ER + and/or PR+, HER2-, Ki-67 <14, any CK 5/6, any EGFR), luminal B (ER + and/or PR+, HER2-, Ki-67 ≥14, any CK 5/6, any EGFR), HER2-enriched (ER-, PR-, HER2+, any Ki-67, any CK 5/6, any EGFR), Luminal-HER2 (ER + and/or PR+, HER2+, any Ki-67, any CK 5/6, any EGFR), Basal-like (ER-, PR-, HER2-, any Ki-67, CK5/6+ and/or EGFR+), triple-negative nonbasal (ER-, PR-, HER2-, any Ki-67, CK 5/6-, EGFR-). Each four- or six-marker defined intrinsic subtype was divided in two groups, with Ki-67 <14% or with Ki-67 ≥14%. Recurrence hazard rate function was determined for each intrinsic subtype as a whole and according to Ki-67 value.

Results

Luminal A displayed a slow risk increase, reaching its maximum after three years and then remained steady. Luminal B presented most of its relapses during the first five years. HER2-enriched tumors show a peak of recurrence nearly twenty months post-surgery, with a greater risk in Ki-67 ≥14%. However a second peak occurred at 72 months but the risk magnitude was greater in Ki-67 <14%. Triple negative tumors with low proliferation rate display a smooth risk curve, but with Ki-67 ≥14% show sharp peak at nearly 18 months.

Conclusions

Each intrinsic subtype has a particular pattern of relapses over time which change depending on the level of activation of the proliferation pathway assessed by Ki-67. These findings could have clinical implications both on adjuvant treatment trial design and on the recommendations concerning the surveillance of patients.     

Up-Regulation of the Inflammatory Response by Ovariectomy in Collagen-Induced Arthritis. Effects of Tin Protoporphyrin IX

We have studied the influence of ovariectomy on the inflammatory response and bone metabolism on CIA as a model of postmenopausal arthritis as well as the effects of tin protoporphyrin IX (SnPP), a heme oxygenase inhibitor. Ovariectomy in non-arthritic mice produced increased serum PGD₂ levels and up-regulated the expression of COX-2, h-PGDS, l-PGDS, and HO-1 in the joints. In CIA, ovariectomy potentiated the inflammatory response with higher levels of serum IL-6 and MMP-3, local PGD₂ and MMP-3 as well as trabecular bone erosion. In OVX-CIA, SnPP decreased the serum levels of IL-6, MMP-3, and PGD₂; down-regulated TNFα, COX-2, hPGDS, PGD₂, PGE₂, and MMP-3 in joint tissues; and also decreased focal bone loss in the inflamed joint. Ovariectomy up-regulates inflammatory mediators in non-arthritic and in arthritic animals. In the OVX-CIA model, SnPP exerts anti-inflammatory effects which are not associated with the prevention of systemic bone loss.