Structural variation of the 3-acetamido-4,5,6-trihydroxyazepane iminosugar through epimerization and C-alkylation leads to low micromolar HexAB and NagZ inhibitors.

We report the synthesis of seven-membered iminosugars derived from a 3S-acetamido-4R,5R,6S-trihydroxyazepane scaffold and their evaluation as inhibitors of functionally related exo-N-acetylhexosaminidases including human O-GlcNAcase (OGA), human lysosomal ß-hexosaminidase (HexAB), and Escherichia coli NagZ. Capitalizing on the flexibility of azepanes and the active site tolerances of hexosaminidases, we explore the effects of epimerization of stereocenters at C-3, C-5 and C-6 and C-alkylation at the C-2 or C-7 positions. Accordingly, epimerization at C-6 (L-ido) and at C-5 (D-galacto) led to selective HexAB inhibitors whereas introduction of a propyl group at C-7 on the C-3 epimer furnished a potent NagZ inhibitor.

Laparoscopic adenomectomy: 10 years of experience. / Adenomectomía laparoscópica: 10 años de experiencia.

INTRODUCTION: Lower urinary tract symptoms secondary to increased prostate volume are associated with ageing and are becoming more prevalent due to increased life expectancy. We present our experience with transperitoneal laparoscopic adenomectomy for the management of bladder outlet obstruction caused by benign prostatic enlargement. MATERIALS AND METHODS: We performed a retrospective review of patients who underwent laparoscopic adenomectomy between 2005 and 2015. We recorded age, maximum flow and postvoid residual urine (preoperative and postoperative), surgical time, operative bleeding, weight and pathology, complications and duration of catheterisation and hospitalisation. RESULTS: We included 80 patients with a mean age of 70 years. The mean preoperative and postoperative Qmax was 8.21mL/s and 22.52mL/s, respectively. The mean preoperative and postoperative postvoid residual urine was 91.4mL and 14.2mL, respectively. The mean surgical time was 137.7min. Conversion to open surgery was necessary in one case due to intestinal injury. The mean intraoperative bleeding was 227.6mL. The mean hospital stay was 5.46 days, and the catheterisation time was 4.86 days. There were 13 complications, which were recorded according to the Clavien-Dindo system, 3 of which were severe. The mean weight of the surgical specimen was 80.02g. Pathology showed benign hyperplasia in 75 cases and prostate cancer in the remaining 5. CONCLUSION: Laparoscopic adenomectomy is a safe, reproducible technique with the same functional results as open surgery. Our series shows that this approach is useful and safe and has a low rate of complications.

Prenatal microarray comparative genomic hybridization: Experience from the two first years of activity at the Lyon university-hospital.

OBJECTIVES: This study aims to describe how microarray comparative genomic hybridization (aCGH) has shifted to become a prenatal diagnosis tool at the Lyon university-hospital. MATERIALS AND METHODS: This retrospective study included all patients who were referred in the 3 pluridisciplinary centers for prenatal diagnosis of the Lyon university-hospital and who received a prenatal aCGH between June 2013 and June 2015. aCGH was systematically performed in parallel with a karyotype, using the PréCytoNEM array design. RESULTS: A total of 260 microarrays were performed for the following indications: 249 abnormal ultrasounds (95.8%), 7 characterizations of chromosomal rearrangements (2.7%), and 4 twins with no abnormal ultrasounds (1.5%). With a resolution of 1 mega base, we found 235 normal results (90.4%), 23 abnormal results (8.8%) and 2 non-returns (0.8%). For the chromosomal rearrangements visible on the karyotype, aCGH identified all of the 12 unbalanced rearrangements and did not identify the 2 balanced rearrangements. Among the fetuses with normal karyotypes, 11 showed abnormal microarray results, corresponding to unbalanced cryptic chromosomal rearrangements (4.2%). CONCLUSION: Transferring aCGH to a prenatal diagnosis at the Lyon university-hospital has increased the detection rate of chromosomal abnormalities by 4.2% compared to the single karyotype.

Multiprobe Study of the Solid Electrolyte Interphase on Silicon-Based Electrodes in Full-Cell Configuration.

The failure mechanism of silicon-based electrodes has been studied only in a half-cell configuration so far. Here, a combination of 7Li, 19F MAS NMR, XPS, TOF-SIMS, and STEM-EELS, provides an in-depth characterization of the solid electrolyte interphase (SEI) formation on the surface of silicon and its evolution upon aging and cycling with LiNi1/3Mn1/3Co1/3O2 as the positive electrode in a full Li-ion cell configuration. This multiprobe approach indicates that the electrolyte degradation process observed in the case of full Li-ion cells exhibits many similarities to what has been observed in the case of half-cells in previous works, in particular during the early stages of the cycling. Like in the case of Si/Li half-cells, the development of the inorganic part of the SEI mostly occurs during the early stage of cycling while an incessant degradation of the organic solvents of the electrolyte occurs upon cycling. However, for extended cycling, all the lithium available for cycling is consumed because of parasitic reactions and is either trapped in an intermediate part of the SEI or in the electrolyte. This nevertheless does not prevent the further degradation of the organic electrolyte solvents, leading to the formation of lithium-free organic degradation products at the extreme surface of the SEI. At this point, without any available lithium left, the cell cannot function properly anymore. Cycled positive and negative electrodes do not show any sign of particles disconnection or clogging of their porosity by electrolyte degradation products and can still function in half-cell configuration. The failure mechanism for full Li-ion cells appears then very different from that known for half-cells and is clearly due to a lack of cyclable lithium because of parasitic reactions occurring before the accumulation of electrolyte degradation products clogs the porosity of the composite electrode or disconnects the active material particles.

[Administering GnRH Agonists in the luteal phase of Artificial Cycle Frozen-Thawed Embryo Transfers. A prospective randomized study]. / Administration d'agonistes de la GnRH (Gonadotrophin Releasing Hormone) en phase lutéale des protocoles substitutifs de transferts d'embryons congelés: étude prospective randomisée.

OBJECTIVE: Adding GnRH agonists in the luteal phase has recently been said to improve implantation in IVF treatment (increased rates of pregnancy and birth). Adding GnRH agonists could also be beneficial for frozen-thawed embryo transfers. The objective was to compare the administration of Gonadotropin Releasing Hormone (GnRH) agonists during implantation with usual progesterone supplementation in the artificial cycle of frozen-thawed embryo transfers. METHODS: A prospective randomized controlled trial was conducted in a reproductive medicine center in a university hospital including all women starting an artificial cycle of Frozen-Thawed Embryo Transfers (FET). Two hundred and twenty women were randomized from September 2013 to June 2014. In the addition of GnRh agonists' group, two triptorelin injections of 0.1mg were carried out on the 4th day and on the 6th day following the introduction of progesterone. The primary outcome was the ongoing pregnancy rate. RESULTS: The ongoing pregnancy rate was higher (17 % versus 10.6 % P=0.29) when triptorelin was added, although the difference wasn't significant for the population as a whole. The increase proved to be significant in the case of day 2 embryos (34.6 % versus 10.3 % P<0.05) and of vitrified blastocysts (33.3% versus 12.5% P<0.05). CONCLUSION: The ongoing pregnancy rate for day 2 embryos and vitrified blastocysts significantly increased when GnRH agonists were added during implantation.

Minimum spread of the new Swedish variant of Chlamydia trachomatis and distribution of C. trachomatis ompA genotypes in three geographically distant areas of Spain, 2011-2012.

PURPOSE: The aim of this study was to determine the presence of the new Swedish Chlamydia trachomatis (C. trachomatis) variant (nvCT) and the distribution of C. trachomatis ompA genotypes in three geographically distant regions of Spain. METHODS: The genotypes of strains causing 624 episodes of infection (January 2011-September 2012) were studied using a nested PCR that amplifies a fragment of the ompA gene, followed by sequencing. To detect nvCT, a real-time PCR was used that amplifies a fragment of the cryptic plasmid with a 377 base pair deletion, which identifies the nvCT. RESULTS AND CONCLUSION: The ompA genotype was identified in 565 (90.5%) episodes. Eleven genotypes were detected, of which nine were found in all three regions. Only one nvCT strain was detected (0.4%), despite the predominance of genotype E (41%). Other frequent genotypes were genotypes D (19%), F (13%), G (11 %), and J (7%). Genotype L2b, causing lymphogranuloma venereum, was detected in men who have sex with men (MSM) in all three regions. Genotypes E and F were more frequent in women and heterosexual men, and genotypes D, G, J and L2b in MSM. In men, the main factor causing differences in the distribution of C. trachomatis was sexual behavior (MSM versus heterosexual men), while the distribution of C. trachomatis genotypes was similar in women and heterosexual men.

[Evolution of open versus laparoscopic/robotic surgery: 10 years of changes in urology]. / Evolución de la cirugía abierta versus laparoscópica/robótica: 10 años de cambios en Urología.

INTRODUCTION: Laparoscopic surgery has been increasingly used in urology in recent years. Laparoscopy has been performed at our center since 2001. Changes over time in the indication of open versus laparoscopic/robotic surgery, hospital stay, and learning curve are reviewed. MATERIALS AND METHODS: A retrospective review of our database from 1997 to the end of 2007. A total of 3622 procedures were performed during this time (endoscopic procedures were excluded): 67.75% open, 26.17% laparoscopic, 2.29% perineal, and 3.78% robotic surgeries. Of these, 83.79% were performed in males and 16.20% in females. Mean patient age was 58.8 years. Data from the study period, including mean hospital stay and changes over time in operating time as a function of the learning curve, were analyzed and compared to data for the last 12 months of the study period. RESULTS: The percentages of all surgical procedures performed using a laparoscopic approach in the 1997-2006 versus the last 12 study months were as follows: nephrectomy, 31.8% versus 74.7%; living donor nephrectomy, 93% versus 100%; nephroureterectomy, 28.1% vs. 93.4%; partial nephrectomy, 31.3% vs 87%; and radical prostatectomy, 17.6% versus 73.5% including laparoscopic and robotic approaches. Shorter mean hospital stays and operating times were also seen. CONCLUSIONS: Use of the laparoscopic approach has greatly increased in the 10-year period studied. In renal surgery, few indications remain for open surgery. In prostate surgery, introduction of robotic surgery in 2005 and learning of laparoscopy by several of our urologists have dramatically changed the therapeutic approach. Gradual incorporation of laparoscopic surgery has led to a decreased hospital stay and to a shortening of the learning curve.

[Questionnaire for urological emergency room quality evaluation]. / Cuestionario de evaluación de la calidad asistencial en un servicio de urgencias urológicas.

INTRODUCTION: Quality is defined as an essential and distinguishing attribute of something, which allows to evaluate its worth. The quality evaluation has become something necessary during the last years. The assistencial quality should be something inherent to the offered service, including scientific and technical quality, management and quality noticed. A periodical assesment, as auto-evaluation or through an outsourcing, is a recommendable way to detect potential improvement items. MATERIAL AND METHODS: Using the EFQM,ISO 9001:2000 and Malcolm Baldrige model, and through the items from National Health System, a self-questionnaire of urological emergency room quality evaluation is proposed. CONCLUSION: A new self-questionnaire of urological emergency room quality evaluation is proposed.

[Algorithm for the treatment of patients with obstructive uropathy secondary to prostate cancer]. / Algoritmo para el manejo de pacientes con uropatía obstructiva secundaria a cáncer de próstata.

BACKGROUND: One of the prostate cancer progression complications is the obstructive uropathy, by infiltration and compression of the distal ureteral section, that can entail to an acute renal insufficiency, with affectation of the quality of life and the survival of these patients. The treatment of prostate cancer with secondary ureterohidronefrosis is palliative and following the present tendencies, the positioning of a nephrostomy is considered. MATERIALS AND METHODS: A search was made in PUBMED and the most representative articles were reviewed. The algorithm was constructed with the daily routine clinical base, the protocol of our center and with the scientific evidence available in medical literature. RESULTS: An algorithm of decisions sets out to define the urinary derivation in patients with obstructive uropathy secondary to prostate cancer. CONCLUSIONS: The indication to place a nephrostomy in patients with obstructive uropathy secondary to prostate cancer must be approached individually, according to the general conditions and the quality of life of the patient with base in scales defined in literature (ECOG and Karnofsky) and in factors of good or bad prognosis, always considering ethical considerations and the consent of the patient and his family.

[Lasers in urology]. / Láser en urología.

UNLABELLED: The objective of this article is to quote under the form of a document the opinions expressed by the participants of the round table "Lasers in Urology Today" (january 2006). The material and method used is the compilation of critical and updated notions on the usefulness of lasers in urology, supplemented by bibliographic references, a limited iconography. The results achieved by lasers today enable us to state that: Holmium laser is the choice treatment for in situ lithotripsy; however, it has not significantly improved previous results when treating urologic tumours and stenoses. Nowadays we have two types of lasers: KTP and HoL, which obtain results similar to surgery regarding BPH, but with reduced morbidity. The usefulness of laser in laparoscopic surgery is still under development. CONCLUSION: Lasers in Urology Today play an active role in in situ lithotripsy (HoL), and a competitive one in BPH surgery (KTP and HoL). Regarding the rest of indications, i.e. tumours, stenoses, laparoscopic surgery, etc., further studies and enough follow-up times are still needed.

[Ovarian tissue vitrification: Cortex and whole ovary in sheep]. / Vitrification du tissu ovarien: cortex et ovaire entier chez la brebis.

OBJECTIVE: The aim of this study was to evaluate a cryopreservation technique by vitrification of cortex or whole ovaries in sheep, using two cryoprotectant solutions: VS1 and VS4 and to study their physical properties to avoid ice crystallisation by vitrification of whole sheep ovaries permeated with a cryoprotectant solution. ANIMALS AND METHODS: From 6-month-old ewes, whole sheep ovaries with their vascular pedicles were collected at the slaughterhouse or at the veterinary school and prepared for cryoprotectant toxicity tests and freezing procedure. Follicle viability was measured by trypan blue test and histological examination of ovary. The hemi-ovarian cortex was stored in liquid nitrogen. Four to six weeks after the first laparotomy, the controlateral ovary was removed and the vitrified-warmed hemi-ovary was sutured. Thermal properties of a cryoprotectant solution called VS4 (critical cooling rates [Vccr], vitreous transition temperature [Tg], end of melting temperature [Tm]) were measured by differential scanning calorimetry. RESULTS: No significant difference in follicle viability or normal follicle rates was observed between ovarian cortex exposed or non-exposed to cryoprotectant solutions. Nor was any significant difference observed before and after vitrification. Three pregnancies occurred, from which four lambs were born after autografts of vitrified ovarian cortex. With whole ovary, the decrease in the number of normal follicles was lower when frozen-thawed ovaries were treated with VS4 (P = 0.04). There were less nuclear anomalies (P = 0.02). The Vccr of VS4 has been estimated to be 14.3+/-1.1 degrees C/min and Tg was -125.0+/-0.2 degrees C. Because the penetration of cryoprotectants was very low, Vccr was very high and the cooling speed did not allow cortex to vitrify. DISCUSSION AND CONCLUSIONS: Cryopreservation of cortex or whole ovary by vitrification seems a promising technique in reproductive medicine. The best histologic results were obtained with the VS4 cryoprotectant when whole ovary was vitrified.

[Transperitoneal laparoscopic partial nephrectomy in the renal tumor treatment]. / Nefrectomía parcial laparoscópica transperitoneal en el tratamiento del tumor renal.

Laparoscopic surgery is a surgical technique the urologist should add to his surgical armamentarium. Its performance tries to mimic the surgical phases of open surgery, and also its indications. Laparoscopic partial nephrectomy is a sophisticated technique that requires wide experience in the performance of endoscopic strategies. We are submitting our experience with 35 laparoscopic partial transperitoneal nephrectomies with a mean follow-up of 25 months. The mean surgical time was 200 minutes, the mean bleeding 190 cc, and the mean hospitalisation five days. Two postoperative bleedings were identified, there were no conversions, and positive margins were notified in two cases, where upon a conservative attitude was adopted.

[Percutaneous treatment with BCG in multiple upper tract transitional cell carcinoma]. / BCG terapéutica por vía percutánea en el tratamiento del carcinoma urotelial múltiple de via superior.

Upper tract transitional cell carcinoma is a low prevalent tumour and frequently associated to bladder carcinoma. The antegrade endoscopic access represents a safe, efficient and minimally invasive access. The association to immunotherapy seems effective in decreasing recurrence. We present one patient with multiple upper tract carcinoma treated with percutaneous surgery and BCG.

Reproducibility of transvaginal three-dimensional endometrial volume measurements with virtual organ computer-aided analysis (VOCAL) during ovarian stimulation.

OBJECTIVE: To calculate inter- and intraobserver reliabilities for three-dimensional endometrial volume measurements during in vitro fertilization using virtual organ computer-aided analysis (VOCAL). PATIENTS AND METHODS: Three-dimensional ultrasound measurements of the endometrium using VOCAL software were performed on the day of oocyte retrieval in each of 79 consecutive patients undergoing in vitro fertilization or intracytoplasmic sperm injection. Endometrial volume was calculated every 15 degrees and every 30 degrees by two different observers in order to determine the reproducibility of the technique. RESULTS: Intraobserver reliability for the 15 degrees measurements was 0.97 for both observers; for the 30 degrees measurements, it was 0.93 for one observer and 0.96 for the other. Interobserver reliability was 0.80 for the endometrial volumes calculated every 15 degrees and 0.83 for the volumes calculated every 30 degrees. The intra- and interobserver measurement agreement showed good reproducibility. However, the volumes calculated every 15 degrees were more accurate because the means of differences were close to zero. CONCLUSION: VOCAL provides a reproducible method for the estimation of the endometrial volume.

[Intracranial metastasis in prostatic cancer]. / Metástasis intracraneales en cáncer de próstata.

The intracranial metastasis due to prostatic adenocarcinoma are quite rare, inside them, the ones placed in the parasellar region on the cranial base are exceptional. There are only 3 clinical cases found in the literature consulted, now we report here two more cases and we review the etiopathogenia, clinic presentation, diagnosis and treatment for this type of lesions. Usually there are very undifferentiated neoplasms, developed stages and with multiple metastasis at others levels. A patient with prostatic carcinoma known and neurological signs we should suspect the presence of intracranial metastasis. The diagnosis is made with image tests (basically with CT and MRI), being necessary in some cases the histological confirmation with a biopsy. Although the prognostic of these patients (less than 6 months in our cases) depends more of the evolutive stage of the illness than the type of treatment that the patients will be someated, we should establish it rapidly, on this way we can revert the neurological status and we will improve the quality of life of these patients.