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Biomedical subjects

C Bourgain

Publications and source records attributed to C Bourgain.

At least 19 recordsLinked to original sources
PubMed2007

Effect of oral administration of dydrogestrone versus vaginal administration of natural micronized progesterone on the secretory transformation of endometrium and luteal endocrine profile in patients with premature ovarian failure: a proof of concept.

BACKGROUND: We aimed to explore the endometrial histology and endocrine profiles on day 21 of an artificial cycle in patients with premature ovarian failure (POF) treated with oral dydrogesterone (DG) or vaginal micronized progesterone. METHODS: The study was designed as a prospective pilot study at an academic reproductive medicine unit. Six POF patients were included in the study. After estrogen endometrial priming, patients were randomized to receive DG or progesterone in two subsequent cycles. The main outcome measure was the endometrial histology and the endocrine profiles on day 21 of the cycle. RESULTS: Development of endometrial glands corresponded to an early secretory phase in five out of six cases supplemented with DG (out-phase). In contrast, five out of six cases treated with micronized progesterone showed an endometrium corresponding to a mid-luteal phase (in-phase) (P = 0.021 versus DG). There was a significant difference in the mean progesterone value [8.6 versus 0.3 microg l(-1) (P = 0.013)], the mean LH value [12.9 versus 22.5 IU l(-1) (P = 0.049)] and the mean FSH value [13.0 versus 23.9 IU l(-1) (P = 0.047)] between the progesterone and DG group, respectively, on day 21 of the cycle. CONCLUSIONS: After estrogen endometrial priming in POF patients, exogenous vaginal micronized progesterone is more effective than oral DG in creating an 'in-phase' secretory endometrium and induces significantly higher progesterone and lower LH and FSH serum concentrations on day 21 of the cycle.

Administration, Intravaginal↗
PubMed2005

A persistently recurring peri-urethral soft tissue lesion of the vulva.

Various mesenchymal lesions, some of which have only recently been characterized, may affect the vulva. Because of their apparently shared origin from vulvovaginal mesenchyme, these lesions can resemble one another superficially and can be challenging diagnostically. Clinically, benign lesions and tumor-like conditions may mimic a malignant process because of hypercellularity, mitotic activity, and rapid growth. We report on a 84-year-old diabetic and hypertensive woman who had previously undergone skinning vulvectomy for lichen planus and an embolectomy of the left femoral artery. The patient presented with a rapidly growing vulvar mass. The biopsy showed spindle cell proliferation in a loose myxoid stroma with granulation tissue and a mixed inflammatory infiltrate. Based on histology and immunohistochemistry, the initial diagnosis was that of a benign lesion. In view of the persistent recurrence of the lesion and the absence of metastatic spread, we conclude that the lesion has a low-grade malignant potential and suggest the diagnosis of florid cellular reactive pseudosarcomatous myofibroblastic proliferation.

Aged↗
PubMed2005

Primary lymphoma of the cervix uteri: a diagnostic challenge. Report of two cases and review of the literature.

BACKGROUND: Primary non Hodgkin's lymphoma (NHL) of the cervix and vagina is uncommon; the incidence of uterine lymphoma is estimated to be less than 0.5% of all NHL. Patients regularly present with vaginal bleeding. The diagnosis is made on biopsy but this can be difficult on small samples which may not be representative of the lesion. Immunohistochemical analysis and often molecular techniques are required to confirm the diagnosis. CASES: We report two cases of primary diffuse large B-cell lymphoma of the cervix. In the first case, the diagnosis could only be made on repeat biopsies. The second case presented as a cervical polyp. CONCLUSION: Gynecologists should be aware of this rare clinical entity in order to apply the proper treatment.

Adult↗
PubMed2004

Low-grade endometrial stromal sarcoma treated with the aromatase inhibitor letrozole.

BACKGROUND: Low-grade endometrial stromal sarcoma is an indolent steroid responsive tumor. Successful hormonal treatment, most commonly with megestrol acetate, has been reported. CASE: A 76-year-old woman underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy 25 years earlier allegedly for a benign condition. She presented to us with postrenal kidney failure and a huge pelvic mass compressing both ureters. After transvaginal trough-cut biopsy of the mass, the diagnosis of low-grade endometrial stromal sarcoma with a high expression of alpha-estrogen receptor was made. The patient was treated with letrozole only with a spectacular response. CONCLUSION: To the best of our knowledge, this is the first case for which letrozole was used on long-term basis as first-line hormonal treatment for a recurrent low-grade stromal sarcoma.

Aged↗
PubMed2004

[Endometrial biopsy in the evaluation of endometrial receptivity].

The histological changes underwent by endometrium during a natural menstrual cycle were described more than 50 years ago. Dating yields several methodological flaws, with intra- and inter-observer variability and shows questionable relationship to endometrial receptivity. The best studied endometrial factors involved in implantation include the formation of luminal epithelial "pinopodes", expression of adhesion molecules and of cytokines. Ovarian stimulation for IVF is known to affect luteal phase function. Factors influencing the endometrial receptivity in such cycles are poorly understood. Studies comparing the endometrium in IVF cycles with natural cycle controls have shown premature secretory changes in the postovulatory and early luteal phase of IVF cycles. These findings suggest a profound modification of luteal endometrial development in stimulated cycles. Studies exploring the endometrium within the cycle of embryo transfer have shown a deleterious effect of severe periovulatory maturation advancement exceeding 3 days, as no clinical pregnancies were observed in this condition.

Biomarkers↗
PubMed2002

Missing data in haplotype analysis: a study on the MILC method.

Given the enormous progress in the knowledge of the human genome, genetic markers are now available throughout the genome. Haplotype analysis, allowing the simultaneous use of information from several markers, has thus become increasingly popular. However, we often face the problem of missing data and of haplotype identification. We have proposed a haplotype based method for the genetic study of multifactorial diseases in founder populations, the MILC method (Bourgain et al. 2000). MILC is based on the contrast of identity length between haplotypes transmitted to affected offspring and haplotype non-transmitted. In this study, the impact of different strategies, regarding missing data, on the MLIC method are evaluated. A real situation is considered where data are derived from a genome screen for asthma susceptibility alleles in the Hutterites. Results are illustrated on this asthma data set.

Asthma↗
PubMed2002

CD80 (B7-1) and CD86 (B7-2) genes and genetic susceptibility to coeliac disease.

The role of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) in T-cell activation makes them good candidates for coeliac disease susceptibility genes. We conducted a genetic linkage study of the CD80/86 gene region in the general Finnish population and in a local subisolate. No linkage was found in either population.

Antigens, CD↗
PubMed2001

Loss of nuclear BRCA1 localization in breast carcinoma is age dependent.

Abstract. Patients carrying a germ line mutation in the BRCA1 gene are predisposed to breast cancer. Somatic BRCA1 mutations were almost never reported in sporadic breast tumors, but several authors have described a decrease in BRCA1 mRNA and protein. In order to further investigate the possible role of BRCA1 in sporadic breast cancer, an improved immunohistochemical protocol was developed and applied on tissue sections obtained from 102 cancer patients belonging to two nonoverlapping age groups (less than 40 and more than 60 years). Based on the obtained BRCA1 specific nuclear staining we could distinguish two categories of breast cancer. The staining was present in almost all the nuclei of the normal and the cancer cells in about 50% of young (less than 40 years old) as well as older patients (more than 60 years old). Thus, BRCA1 does not seem to be involved in the genesis of these cancers. In the second category of patients, either a fraction of, or all tumor cells showed no nuclear staining. In this category, no nuclear BRCA1 staining could be observed in the tumor cells of 14 (27%) young and 3 (6%) older patients. Among six young patients bearing a breast tumor showing no BRCA1 nuclear staining at all, one was found to carry a BRCA1 germline mutation. Taken together, our results suggest that the molecular pathway in which the BRCA1 protein participates is disturbed in about 50% of sporadic breast cancer, this effect being more pronounced in tumors of young patients.

Adenocarcinoma↗
PubMed2001

Transduction of ovarian cancer cells: a recombinant adeno-associated viral vector compared to an adenoviral vector.

Recombinant adeno-associated virus (rAAV) vectors have emerged as vehicles for gene therapy. In addition, anti-neoplastic properties have been attributed to wild-type AAV. To take advantage of both features and to overcome technical problems associated with rAAV preparation, we developed a production method in which rAAV particles are amplified in an infectious cycle in the presence of wtAAV. This results in a 10(3)-10(4)-fold amplification of rAAV input particles. rAAV-GFP particles generated by this method were used to transduce ovarian cancer cell lines to evaluate their potential in ovarian cancer gene therapy, in comparison to a rAd-GFP vector. The transduction efficiency of NIH-OVCAR3, MDAH 2774 and SKOV3 cells with rAAV-GFP particles was low (< 1%) and did not improve by increasing the number of particles/cell. Repeated administration and continued exposure of NIH-OVCAR3 and MDAH 2774 improved transduction to over 3%. In contrast, these cell lines were more efficiently transduced by rAAV-GFP in the presence of adenovirus (approximately 15%) and by rAd-GFP (> 50%). These results indicate that in contrast to rAd vectors, rAAV particles are not suitable for therapeutic gene transfer in ovarian cancer cells unless efficient help can be provided to mediate ss to ds DNA conversion.

Adenoviridae↗
PubMed2001

Maximum identity length contrast: a powerful method for susceptibility gene detection in isolated populations.

We report the results of our analysis of the Genetic Analysis Workshop 12 simulated data set. Focusing on the isolated populations, we compare the efficiency of a new method, the maximum identity length contrast statistic (MILC) with the maximum likelihood score (MLS) in a genome screen strategy. MILC is a method based on the contrast of haplotype identity between transmitted and nontransmitted haplotypes in trios. It uses information on linkage and association. We found that MILC allows the detection of a risk factor corresponding to candidate gene 1 where the MLS fails, though the same population replicates were used. Interestingly, the association between this risk factor and the disease could not have been detected with the TDT at a genome-wide level.

Chromosome Mapping↗
PubMed2001

Ovulation induction disrupts luteal phase function.

Abnormalities in the luteal phase have been detected in virtually all the stimulation protocols used in in vitro fertilization, on both the hormonal and endometrial levels. Supraphysiological follicular or luteal sex steroid serum concentrations, altered estradiol: progesterone (E2/P) ratio, and disturbed luteinizing hormone pituitary secretion leading to corpus luteum insufficiency or a direct drug effect have been postulated as the main etiologic factors. Luteinizing hormone supports corpus luteum function, and low LH levels have been described after human menopausal gonadotropin treatment, after gonadotropin-releasing hormone (GnRH)-agonist treatment, or after GnRH-antagonist treatment. These low luteal LH levels may lead to an insufficient corpus luteum function and consequently to a shortened luteal phase or to the low luteal progesterone concentrations frequently described after ovulation induction. A direct effect of the GnRH agonist or GnRH antagonist on human corpus luteum or on human endometrium and thus on endometrial receptivity cannot be excluded, as GnRH receptors have been described in both compartments. Endometrial histology has revealed a wide range of abnormalities during the various stimulation protocols. In GnRH-agonist cycles, mid-luteal biopsies have revealed increased glandulo-stromal dyssynchrony and delay in endometrial development, strong positivity of endometrial glands for progesterone receptors, decreased alphavbeta3-integrin subunit expression, and earlier appearance of surface epithelium pinopodes. These factors suggest a shift forwards of the implantation window. Progesterone supplementation improves endometrial histology, and its necessity has been well established, at least in cycles using GnRH agonists.

Endometrium↗
PubMed2000

Use of closely related affected individuals for the genetic study of complex diseases in founder populations.

We propose a method, the maximum identity length contrast (MILC) statistic, to locate genetic risk factors for complex diseases in founder populations. The MILC approach compares the identity length of parental haplotypes that are transmitted to affected offspring with the identity length of those that are not transmitted to affected offspring. Initially, the statistical properties of the method were assessed using randomly selected affected individuals with unknown relationship. Because both nuclear families with multiple affected sibs and large pedigrees are often available in founder populations, we performed simulations to investigate the properties of the MILC statistic in the presence of closely related affected individuals. The simulation showed that the use of closely related affected individuals greatly enhances the power of the statistic. For a given sample size and type I error, the use of affected sib pairs, instead of affected individuals randomly selected from the population, could increase the power by a factor of two. This increase was related to an increase of kinship-coefficient contrast between haplotype groups when closely related individuals were considered. The MILC approach allows the simultaneous use of affected individuals from a founder population and affected individuals with any kind of relationship, close or remote. We used the MILC approach to analyze the role of HLA in celiac disease and showed that the effect of HLA may be detected with the MILC approach by typing only 11 affected individuals, who were part of a single large Finnish pedigree.

Celiac Disease↗
PubMed2000

Difficulties in the management of an incomplete form of refractory thrombotic thrombocytopenic purpura, the usefulness of vincristine.

BACKGROUND: Although several etiologies can be identified in thrombotic thrombocytopenic purpura (TTP), idiopathic cases are still frequent. Incomplete forms are more rare. Currently, the diagnosis may be made in cases of thrombocytopenia and microangiopathic hemolytic anemia. According to the literature, mortality and morbidity are significantly improved with plasma exchange. However, treatment in refractory forms remains problematic. CASE REPORT: A 33-year old woman presented with an incomplete form of TTP, refractory to a combination of therapeutics. The patient underwent plasma infusion, plasma exchange, and then was started on corticosteroids. She also received intravenous immunoglobulins and antiplatelet agents in close proximity to vincristine (Oncovin) infusion. The main biological indicators used were the platelet count, hematocrit, LDH, and the presence of schistocytes. Following vincristine treatment, the patient's condition rapidly improved. CONCLUSION: Vincristine administered after the failure of standard therapeutics was effective in this refractory form of TTP.

Adrenal Cortex Hormones↗
PubMed2000

Search for multifactorial disease susceptibility genes in founder populations.

The current challenge in biomedical research is to detect genetic risk factors involved in common complex diseases. The power to detect their role is generally poor in populations that have been large for a long time. It has been suggested that the power may be increased by taking advantage of the specificity of founder populations: linkage disequilibrium spanning larger regions and kinship coefficients being stronger than in large populations. A new method is proposed here, the Maximum Identity Length Contrast (MILC) which, in contrast with other existing methods, does not make the assumption of unique ancestry for the genetic risk factors. It is thus appropriate for a search for common genetic risk factors for complex diseases. Statistical properties of the method are discussed in realistic contexts.

Founder Effect↗
PubMed1999

Alteration of jun proto-oncogene status by plasmid transfection affects growth of human ovarian cancer cells.

The AP-1 transcription factor (the Jun and Fos proteins) is suspected of playing an important role in the biology of human cancer. Human epithelial ovarian tumors and cancer cell lines express the c-jun and jun-B proto-oncogenes at a high level, in contrast with the jun-D gene. We have investigated here the functional relevance of these observations for the growth of ovarian cancer cells. Transient constitutive expression of a dominant negative c-jun mutant (TAM67) in human AZ224, SKOV3 and OVCAR3 ovarian cancer cells inhibited the outgrowth of selection marker-resistant colonies by at least 75% as opposed to a control plasmid. Transfection of jun-B did not affect these cell lines, while jun-D transfection had a cell line-specific effect. In comparison, transfection of the tumor-suppressor gene p53 had a less important inhibitory effect on OVCAR3 cells and no effect on SKOV3 and AZ224 cells when compared to TAM67. Regulated TAM67 expression in AZ224 cells, from plasmids containing the mouse metallothionein or the MMTV promoter, suppressed cancer cell growth in vitro and in nude mice without evidence of increased cell death. Our observations support a role for the c-jun proto-oncogene as a positive mediator of human ovarian cancer cell growth and make it a potential therapeutic target.

Animals↗