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Biomedical subjects

J L Leroy

Publications and source records attributed to J L Leroy.

At least 19 recordsLinked to original sources

The new 4DDome prosthesis: an original light and partially absorbable composite mesh for hernia repair.

INTRODUCTION: The use of non-absorbable meshes for the repair of inguinal hernias has become standard; however, these meshes have been associated with complications including long-term postoperative pain. To this end, a new partially absorbable composite mesh has been developed, and the aim of this study was to investigate its efficacy in animal and human trials. MATERIALS AND METHODS: Sixty male Wistar rats were used to evaluate the behavior of the newly designed composite mesh. Composite meshes were implanted in the extra-peritoneal plane for 2, 4 and 8 weeks and compared to a standard polypropylene mesh. Forty patients with symptomatic inguinal hernias were treated using a new 4DDome designed prosthesis. Follow-up was by clinical and ultrasound examination at 1, 6 and 12 months. RESULTS: The animal study demonstrated that the inflammatory reaction associated with the new composite mesh was significantly lower than a standard polypropylene mesh, characterized by a lower macrophage infiltrate (P < 0.001). The mesh did not shrink over the 8-week period, unlike the polypropylene mesh (P < 0.05). The human study showed that there were three minor postoperative complications, no recurrences and the mesh was well tolerated. Follow-up with serial ultrasound showed that at 10 days and 1 month the dome was clearly visible in position; however, by 6 months it had flattened out, been partially absorbed and become incorporated into the repair. CONCLUSION: These experimental and clinical studies have validated the concept of the new 4DDome composite mesh. It was well tolerated and was associated with good short-term results. The combination of the dome shape and the new composite mesh means that less polypropylene is required and represents a significant advance in anterior hernia repair.

Animals↗

Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions.

OBJECTIVE: The aim of the study was to evaluate human papillomavirus (HPV) testing during the follow-up of patients after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesion. METHODS: A prospective study was conducted on 205 patients who underwent conization for high-grade squamous intraepithelial lesion (CIN 2 or 3). Loop electrosurgical excision procedure (LEEP) was used in all cases. High-risk HPV testing was realized by the Hybrid Capture II system before and 3 months after conization. RESULTS: Of the 205 patients, 193 (94.1%) were positive for the HPV test before conization. Seventy-one were HPV positive after conization (34.6%). The margins were positive in 36.1%. Residual disease was observed in 27 cases (13.2%). Four patients (2%) developed a recurrence after a mean follow-up of 18.1 months (+/-12). There was no correlation between pretreatment HPV testing and the residual disease or recurrence. Patients with positive margins were significantly more likely to have residual disease than those with negative margins (P < 0.0001). Residual disease was more likely to occur when the posttreatment HPV test was positive (P < 10(-7)). All recurrences were observed in patients with a positive posttreatment HPV test (P < 0.05). Residual disease and recurrence were correctly predicted with a sensitivity of 81 and 100%, respectively, and a negative predictive value of 96 and 100%. CONCLUSION: Posttreatment HPV testing could be useful in the follow-up of patients after conization. In case of negative posttreatment HPV testing, the frequency of follow-up could be reduced, particularly in those patients with free margins.

Adolescent↗

[Cytological history of 148 women presenting with invasive cervical cancer].

OBJECTIVES: The aim of this study was to analyse the cytological history of women presenting with invasive cervical cancer. MATERIAL AND METHODS: Retrospective study of 148 patients treated for invasive cervical cancer in three hospitals of the North Pas de Calais in France. RESULTS: The average age of patients was 49 (26-86). Squamous carcinomas represented 81% of cases (120/148), adenocarcinomas 17% (25/148) and adenosquamous carcinomas 2% (3/148). 36.5% of patients (54/148) had never had a Pap smear. 34.5% (51/148) had had an occasional Pap smear (the last one dated of more than three years). 8.1% (12/148) were lost for follow up after a positive Pap smear. 3.4% (5/148) were treated for cervical dysplasia less than three years before the diagnosis of the cervical cancer. 17.5% (26/148) had had a Pap smear reported as negative less than three years before the diagnosis of the cervical cancer. In this last group, squamous carcinomas represented 57.7% of cases (15/26), adenocarcinomas 38.5% (10/26) and adenosquamous carcinomas 3.8% (1/26). 18 Pap smears of 26 reported as negative less than three years before the diagnosis of the cancer were reviewed. These Pap smears came from 11 patients presenting with squamous carcinoma and seven other presenting with adenocarcinoma. After review, 15 Pap smears were reported as false negatives and two as true negatives. The review was not possible in one case. CONCLUSION: In this study, the failures of cervical cancer screening were essentially attributed to the lack or the insufficiency of screening and the existence of false negatives of the cytology.

Adenocarcinoma↗

[Contribution of ovarian and uterine color Doppler in medically assisted reproduction techniques (ART)].

Along the menstrual cycle and during pregnancy, small blood vessels proliferate within the uterus and the ovulating ovary. Angiogenic factors such as VEGF are involved in this phenomenon. In the ovulating ovary, neo-angiogenesis spreads progressively inside the dominant follicle wall and plays a role in the maintenance of the corpus luteum, under the influence of LH (or HCG during pregnancy). In ART, the measure of the blood flow is interesting since it correlates to the number and quality of harvested oocytes. Follicle hypoxia may impair chromosomal organization and separation within the oocyte. This neo-angiogenesis is also important in endometrium, in particular for embryo implantation. Ultrasounds with Doppler allow to estimate the endometrial receptivity, especially in IVF cycles. It is assumed that chance for ongoing pregnancy is almost zero if: endometrial thickness is < 8 mm; uterine pulsatility index (PI) is > 3. Doppler ultrasounds are a useful and even mandatory complement to standard vaginal ultrasonoghraphy in ART. It can be viewed as an indicator of the endometrial and follicular "well-being".

Endometrium↗

Management of female genital mutilation in Djibouti: the Peltier General hospital experience.

Female genital mutilation (FGM) is still performed on 98% of Djiboutian women. Infibulation (FGM type 3) is the most widely used method of FGM in Djibouti. Even though this operation is mutilating, illegal and sometimes results in death, it is still practiced at approximately the same rate as in the past. Mass immigration of African women to Europe, Canada, Australia and the United States in the past decade has brought the problems of FGM to these countries. Female genital mutilation is a problem unfamiliar to most Western obstetrician-gynecologists. A tight infibulation can be a high risk for the mother and fetus if not handled by a skilled operator. It can lead to an unnecessary cesarean section as a result of the fear of handling infibulated women. Therefore, Western physicians need to be informed. The aim of this article was to share our experience of FGM. It will focus on FGM in Djibouti, its types, epidemiology and health consequences. It will present the management of obstetric and gynecologic complications and discuss medico-legal and health service measures to combat these dangerous and unnecessary practices

Child↗

[Diagnosis of endometrial cancer].

Endometrial cancer, a hormone-related disease with unopposal hyperestrogenemia as one of its major risk factor is usually diagnosed during post menopausal bleeding. Pathologic examination after endometrial biopsy or curettage is mandatory for the diagnosis before any treatment. The 2 first line procedures in the work up are transvaginal ultrasound with colour Doppler and hysteroscopy. Currently, there is not any cost-effective screening test for the early detection of endometrial cancer.

Adult↗

Imino proton exchange and base-pair kinetics in RNA duplexes.

Using NMR magnetization transfer from water and ammonia-catalyzed exchange of the imino proton, we have measured the base-pair lifetimes and the dissociation constants of six RNA duplexes: [r(CGCGAUCGCG)](2), [r(CGCGAAUUCGCG)](2), [r(CCUUUCGAAAGG)](2), [r(CGCACGUGCG)](2), [r(GGU(8)CC).r(GGA(8)CC)], and [poly(rA).poly(rU)], and we compare them with those of their DNA homologues. As predicted by a two-state (closed/open) model of the pair, the imino proton exchange times decrease linearly vs. the inverse of catalyst concentration. As in DNA duplexes, base pairs open one at a time, and the kinetics is in most cases insensitive to the nature of the adjacent residues. The lifetime of the r(G.C) pairs, 40 to 50 ms, is longer than that of the equivalent in the corresponding oligodeoxynucleotides, and the dissociation constants, about 10(-)(7), are slightly smaller. The r(A.U) opening and closing rates are much larger than those of the d(A.T) pairs, but the stabilities are comparable.

Ammonia↗

Structure of a C-rich strand fragment of the human centromeric satellite III: a pH-dependent intercalation topology.

Repetitive DNA sequences may adopt unusual pairing arrangements. At acid to neutral pH, cytidine-rich DNA oligodeoxynucleotides can form the i-motif structure in which two parallel-stranded duplexes with C.C(+) pairs are intercalated head-to-tail. The i-motif may be formed by multimeric associations or by intra-molecular folding, depending on the number of cytidine tracts, the nucleotide sequences between them, and the experimental conditions. We have found that a natural fragment of the human centromeric satellite III, d(CCATTCCATTCCTTTCC), can form two monomeric i-motif structures that differ in their intercalation topology and that are favored at pH values higher (the eta-form) and lower (the lambda-form) than 4.6. The change in intercalation may be related to adenine protonation in the loops. We studied the uridine derivative methylated on the first cytidine base, d(5mCCATTCCAUTCCUTTCC), whose proton spectrum is better resolved. The intercalation topologies are (C7.C17)/(5mC1.C11)/(C6.C16)/(C2.C12) for form lambda and (5mC1.C11)/(C7.C17)/(C2.C12)/(C6.C16) for form eta. We have solved the structure of the eta-form, and we present a model for the lambda-form. The switch from eta to lambda involves disruption of the i-motif. In both forms, the central AUT linker crosses the wide groove, and the first and the third linkers loop across the minor grooves. The i-motif core is extended in the eta-form by the inter-loop reverse Watson-Crick A3.U13 pair, whose dissociation constant is around 10(-2) at 0 degrees C, and in the lambda-form by the interloop T5.T15 pair. In contrast, d(5mCCATTCCTTACCTTTCC) folds into a pH-independent structure that has the same intercalation topology as the lambda-form. The i-motif core is extended below by the interloop T5.T15 pair and closed on top by the T8.A10 pair.Thus, the C-rich strand of the human satellite III tandem repeats, like the G-rich strand, can fold into various compact structures. The relevance of these features to centromeric function remains unknown.

Base Sequence↗

The RNA i-motif.

Oligodeoxynucleotides with stretches of cytidine residues associate into a four-stranded structure, the i-motif, in which two head-to-tail, intercalated, parallel-stranded duplexes are held together by hemiprotonated C.C+ pairs. We have investigated the possibility of forming an i-motif structure with C-rich ribonucleic acids. The four C-rich RNAs studied, r(UC5), r(C5), r(C5U) and r(UC3), associate into multiple intercalated structures at acidic pH. r(UC5) forms two i-motif structures that differ by their intercalation topologies. We report on a structural study of the main form and we analyze the small conformational differences found by comparison with the DNA i-motif. The stacking topology of the main structure avoids one of the six 2'-OH/2'-OH repulsive contacts expected in a fully intercalated structure. The C3'-endo pucker of the RNA sugars and the orientation of the intercalated C.C+ pairs result in a modest widening of the narrow grooves at the steps where the hydroxyl groups are in close contact. The free energy of the RNA i-motif, on average -4 kJ mol(-1) per C.C+ pair, is half of the value found in DNA i-motif structures.

Base Pairing↗

Clinical and radiographic features of multiple epiphyseal dysplasia not linked to the COMP or type IX collagen genes.

Multiple epiphyseal dysplasia (MED) is a mild chondrodysplasia affecting the structural integrity of cartilage and causing early-onset osteoarthrosis in adulthood. The condition is genetically heterogeneous. Mutations in the COMP gene and in two genes (COL9A2; COL9A3), coding respectively for the alpha2(IX) and alpha3(IX) chains of type IX collagen, can cause the autosomal dominant forms of MED. Mutations in the DTDST gene have recently been identified in a recessive form of MED. However, for the majority of MED cases, the genetic defect still remains undetermined. We report a three-generation family with an autosomal dominant form of MED, characterised by normal stature, joint pain in childhood and early-onset osteoarthrosis, affecting mainly the hips and knees. Based on discordant inheritance among affected individuals linkage of the phenotype to the COMP, COL9A1, COL9A2, COL9A3 genes was excluded. Our study provides evidence that at least another locus, distinct from COL9A1, is involved in autosomal dominant MED.

Adolescent↗

Assessment of Fallopian tube patency by HyCoSy: comparison of a positive contrast agent with saline solution.

OBJECTIVE: To compare the efficiency of air-filled albumin microspheres (Infoson) with saline solution in determining Fallopian tube patency during hysterosalpingo contrast sonography (HyCoSy). METHODS: This was a prospective randomized multicenter study with a sequential design. Over a 10-month period, 23 patients (mean age, 33 years) referred for infertility were examined by HyCoSy (saline or Infoson) before conventional hysterosalpingography (Iopamiron 370), performed during the same session. Contrast agents were administered through a 5-F Ackrad balloon catheter inserted transcervically into the uterine cavity. HyCoSy was performed with a 7-MHz transvaginal probe using both B-mode and color Doppler, and tubal patency was demonstrated by the appearance of contrast agent in the peritoneal cavity near the ovaries. Data were registered for each patient during the examination and the results were monitored by sequential analysis. RESULTS: Mean volumes of contrast injections were 35.3 mL of saline, 14.4 mL of Infoson, and 13.8 mL of Iopamiron 370. Infoson-enhanced HyCoSy provided a significantly larger (P = 0.006) number of correct diagnoses (20/22 Fallopian tubes) than did saline HyCoSy (12/24 Fallopian tubes), and the same number as that achieved by hysterosalpingography. CONCLUSION: A positive ultrasound contrast agent appears to be more efficient than saline solution at determining Fallopian tube patency in infertile women by means of HyCoSy, and as efficient as an iodinated contrast agent in the same population explored by HSG. HyCoSy could be used to screen infertile women, thereby avoiding the use of iodinated contrast medium and exposure to ionizing radiation during conventional HSG in patients with patent Fallopian tubes.

Adult↗

The solution structure and internal motions of a fragment of the cytidine-rich strand of the human telomere.

We present the solution structure of d(CCCTA2CCCTA2CCCTA2CCCT), a fragment of the vertebrate telomere which folds intramolecularly. The four cytidine stretches form an i-motif which includes six intercalated C.C+ pairs and terminates with the cytidines at the 5' extremity of each stretch. Above, the second TA2 linker loops across one of the narrow grooves, while at the bottom, the first and third linkers loop across the wide grooves. At 30 degrees C, the spectra of the first and third linkers are quasi-degenerate. Severe broadening at lower temperature indicates that this results from motional averaging between at least two structures of each bottom loop, and makes it impossible to solve the configuration of the bottom loops directly, in contrast to the rest of the structure. We therefore turned to the modified sequence d(CCCTA(2)5MCCCTA2CCCUA2CCCT) in which the two base substitutions (underlined) break the quasi-symmetry between linkers 1 and 3. The three loops follow approximately the hairpin "second pattern" of Hilbers. In the first loop, T4 is in the syn orientation, whereas its analog in the third loop, U16, oriented anti, is in a central location, where it interacts with bases of both loops, thus contributing to their tight association. The only motion is a syn/anti flip of A18 in the third loop. Returning to the telomere fragment, we show that each of the bottom loops switches between the structures identified in the first and third loops of the modified structure. The motions are concerted, and the resulting configurations of the bottom loop cluster present a bulge to either right (T4 syn) or left (T16 syn).

Base Pairing↗

Positive margins after conization and risk of persistent lesion.

OBJECTIVE: The aim of this study was to investigate a method to reduce the frequency of uterine reoperation with no persistent lesion and to identify factors predictive of persistent or recurrent lesions. MATERIALS AND METHODS: Of 505 conizations performed by the same surgeon, 71 had positive margins (average patient age = 35.7 +/- 7.7 years). The patients underwent either immediate reoperation or monitoring with a Pap smear and colposcopy. RESULTS: Histologic assessment of the cervical cone after conization showed positive margins in 14.1% of cases [endocervical and exocervical margins affected in 50 of 505 (9.9%) and 21 of 505 (4.2%) cases, respectively]. Of 59 of these patients (83.1%) who underwent follow-up monitoring over an average of 35.2 months (range: 2.6-180. 8), 12 patients (average age: 40.8 +/- 6.4 years) underwent immediate hysterectomy and 47 (average age 34.0 +/- 7.4 years) benefited from monitoring first [secondary discovery of 19 persistent lesions within 6 months and 9 recurrences within 18 months on average (range: 8.8-48 months)]. Of the 9 patients with recurrent lesions, 7 underwent reintervention and 2 monitoring. Of the 19 patients with persistent lesions, 18 underwent reintervention and 1 monitoring. Normal histology was observed in 29.4% of patients undergoing secondary reoperation for an abnormal smear compared with 66.7% of patients undergoing immediate reoperation (P = 0.04). Severity of lesion and age of patients could not be used to predict the incidence of a persistent or recurring lesion. Seventy-nine percent of conizations had positive endocervical margins in patients with a recurring or persistent lesion compared with 48% in patients with normal follow-up (P = 0.03). CONCLUSION: Cytology and colposcopy follow-up in cases of positive conization margins may help to establish justification for the choice of reoperation, thereby limiting morbidity following repeated surgery.

Adult↗

The i-motif in nucleic acids.

Seven years after the discovery of the DNA i-motif, partial explanations for its occurrence have been uncovered, possibly involving CHellipsisO hydrogen bonds across the narrow grooves. Investigations of its biological significance have been encouraged by the demonstration and description of the intramolecular i-motif structure of human telomeric and centromeric sequences, by the recent observation of an intercalated RNA structure and by the discovery of proteins that associate with DNA sequences carrying cytosine repeats. The compatibility of the intercalation with peptide and phosphorothioate DNA analogs is favorable for possible pharmaceutical applications.

DNA↗

Determination of the residence time of water molecules hydrating B'- DNA and B-DNA, by one-dimensional zero-enhancement nuclear Overhauser effect spectroscopy.

The residence time of water in the minor groove of the d(CGCGAATTCGCG) duplex has been determined by a recent measurement combining nuclear Overhauser enhancements (NOE, ROE) and 17O relaxation dispersion. The time is in the range of nanoseconds, so that it may be measured by a rather simple method proposed here, namely the choice of conditions such that the NOE between the observed DNA proton and a nearby water proton is zero. This condition is realized when the residence time of the water molecule is 0.178 times the nuclear magnetic resonance period (e.g. 0.297 ns at 600 MHz). It may be achieved by varying the magnetic field and/or the temperature. The zero-NOE measurement may be performed by one-dimensional NMR, and has therefore good sensitivity. We have developed excitation sequences which suppress two spurious contributions to the NOE: from neighboring exchangeable protons and from H3' protons whose chemical shift is close to that of water. The method is applied here to the comparison of residence times of water next to B-DNA and next to B'-DNA, the latter corresponding to better stacked, propeller-twisted base-pairs and a correspondingly narrower minor groove. In the minor groove of [d(CGCGAATTCGCG)]2, a B'-DNA duplex, the residence time of the water molecule next to H2 of adenine(6) (underlined), is 0.6 ns at 10 degreesC, in good agreement with the value obtained previously. The residence time is slightly but distinctly shorter for the water next to A5, suggesting non-cooperative departure of these two molecules which are presumed to be part of the hydration spine. Near A5 and A4 of [d(AAAAATTTTT)]2, another B'-DNA duplex, the residence times are approximately twice as long, but the activation enthalpies are about the same, ca. 38 kJ/mol. The residence time in the minor groove of the regular B-DNA sequence d(CGCGATCGCG) was 0.3 ns at 10 degreesC, shorter than in the case of the B'-DNA sequences by factors of 2 and 4, respectively. The temperature dependence is less, with an activation enthalpy of 27 kJ/mol. The major groove residence times are comparable for the three sequences, and a few times shorter than those of minor groove water. A value of 0.36 ns, or even more in case of rotation of water, is obtained around -8 degreesC. The most striking aspect of these results is the relatively small difference in the residence times of reputedly fast and slow-exchanging water molecules bound to DNA in biological conditions. This suggests that the spine of hydration is perhaps not a major stabilizer of the B'-DNA structure as compared with B-DNA.

DNA↗

[The mechanisms of endometriosis].

Endometriosis is characterised by the presence in abnormal situation of a tissue resembling the endometrium with glands and stroma. Several assumptions try to explain the development of this tissue. The oldest, the theory of the metaplasia, suggests that under various influences the coelomic tissues would be transformed into endometrium. Most often agreed, the theory known as the implantation theory, explains why the endometrial cells and fragment desquamated during menstrual period transported through the fallopian tubes into the peritoneal cavity (physiological phenomenon) could under certain conditions implant, proliferate and develop overcoming the local mechanisms of defence. The peritoneal cavity of the normal women have the capacity to prevent the evolution towards endometriosis. The reasons of an evolution towards the endometriosis and its symptoms (pain, sterility, adherences are probably numerous implying the immune system, the endometrium, the macrophages, the cells natural killer, the peritoneum the fallopian tubes. The failure to removes the peritoneal cavity of the fragments would induce an inflammatory local state with hyperactivation of the macrophages which secrete many molecules, of which some could lead the metaplasia of the peritoneum or the development of müllerian residues.

Cell Adhesion↗