Selective head cooling and acute kidney injury in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: The reno-protective effect of therapeutic hypothermia in infants with hypoxic ischemic encephalopathy (HIE) is still debatable. We aimed to study the effect of therapeutic hypothermia on the development and progress of acute kidney injury (AKI) in neonates with HIE. METHODS: Thirty full term infants with HIE were equally distributed between cooling group (selective head cooling) or non-cooling group (late presentation after 6 hours of birth). Serum creatinine, urine output (UOP), serum neutrophil gelatinase-associated lipocalin (NGAL), and serum cystatin C were measured at baseline, day 4 and day 10 of life. RESULTS: The incidence of AKI as per Acute Kidney Injury Network (AKIN) criteria was comparable in cooling and non-cooling groups (40% versus 53%, respectively). Serum creatinine and UOP were significantly improved on day-4 and day-10 samples compared to base-line samples in both groups regardless of cooling. Therapeutic hypothermia was associated with a significant reduction in serum NGAL, but not cystatin C, level in day-4 and day-10 samples compared to the non-cooling group. Serum NGAL and cystatin C did not show a significant decline in day-4 and day-10 samples compared to baseline samples in both the cooled and non-cooled groups indicating an ongoing AKI. CONCLUSIONS: Therapeutic hypothermia was associated with less renal impairment when compared to infants with HIE who were not cooled. Continuing kidney injury may persist in asphyxiated newborns despite improvement in serum creatinine and UOP. TRIAL REGISTRATION NUMBER: NCT02683915.

Preservation of the internal genital organs during radical cystectomy in selected women with bladder cancer: a report on 15 cases with long term follow-up.

PURPOSE: To prospectively present the technique, functional and oncological outcome of internal genitalia sparing cystectomy for bladder cancer in 15 selected women. PATIENTS AND METHODS: Between January 1995 and December 2010, 305 women underwent orthotopic neobladder after radical cystectomy. Of these, 15 cases with a mean age of 42 years underwent genitalia sparing. Inclusion criteria included stage (T2b N0 Mo or less, as assessed preoperatively, unifocal tumors away from the trigone, sexually active young women and internal genitalia free of tumor. Cystectomy with preservation of the uterus, vagina and ovaries and Hautmann neobladder were performed. Oncological, functional, urodynamic and sexual outcome using Female Sexual Function Index (FSFI) were evaluated. RESULTS: Definitive histopathology showed advanced stage not recognized preoperatively in 2 patients, who developed local recurrence and bony metastasis after 3-4 months. A third patient developed bony metastasis after 15 months. No recurrence developed in the retained genital organs. The remaining 12 patients remained free of disease with a mean follow-up of 70 months. Among women eligible for functional evaluation, daytime and nighttime continence were achieved in 13/13 (100%) and 12/13 (92)%, respectively. Chronic urinary retention was not noted. The urodynamic parameters were comparable to those in other patients without genital preservation. Sexual function (FSFI) was better in these patients than in others without genital preservation. CONCLUSIONS: Genital sparing cystectomy for bladder cancer is feasible in selected women. It provides a good functional outcome, better sexual function and the potential for fertility preservation. So far, the oncological outcome is favorable.

CAG repeat length in androgen receptor gene and male infertility in Egyptian patients.

The CAG repeat and its association with infertility has been debatable. Therefore, this study was planned to assess the distribution of CAG repeat expansion in Egyptian patients and to investigate its association with male infertility. Forty-five infertile men were eligible for the study in addition to 20 aged-matched fertile males as control. Semen analysis, scrotal sonography, assay of serum testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH), and determination of the CAG repeat number within exon 1 of the androgen receptor (AR) gene were carried out. Statistically significant difference was found between infertile and control groups regarding sperm count, sperm motility, serum FSH level and CAG repeats (P < 0.05); statistically insignificant difference for the CAG repeats (P = 1.0) was found between oligozoospermic and asthenospermic groups; negative correlation was found between CAG repeat length and sperm count, and a positive correlation was found between CAG repeat length and serum FSH (P < 0.05). Our results validate the concept that long stretches of CAG repeat may be associated with lower AR function with derangement of sperm production, and this may contribute to male infertility in Egyptian men.

Penile haemodynamic changes in post-radical cystectomy patients.

The aim of this study was to assess the penile vascular changes in post-radical cystectomy patients. A prospective assessment took place between January 2003 and January 2005 of 45 potent men who underwent radical cystectomy and diversion for invasive bladder cancer. Nerve sparing (NS) technique was applied in 21 cases, while others were not subjected to NS (non-nerve sparing group; NNS = 24 cases). All patients were comparable in preoperative clinical and pathological parameters. A control arm was the preoperative normal indices of the same patients. Preoperative penile duplex ultrasounds (PDU) for all cases were carried out, and then follow-up 2, 6 and 12 months thereafter. On first postoperative visit, none of NS cases showed any arterial insufficiency, while two cases of NNS (8.3%) had peak systolic velocity (PSV) < 30 cm/sec. Moreover, all cases of both groups showed early increase of end diastolic velocity (EDV) > 5 cm/sec. In NS cystectomy group, the PSV showed statistically insignificant change [p > 0.05 (mean: 53.6, cm/sec)]. Shortly after surgery, the EDV values increased, followed by gradually significant improvement (decrease in EDV values) in comparison with control state (mean: 5.9 cm/sec). On the other hand, the NNS cases showed statistically insignificant changes in PSV (mean: 49.3 cm/sec), with deterioration in EDV that did not improve with time, in contrast to NS cases (mean: 13.15 cm/sec). The main significant penile vascular changes were in EDV (venogenic mechanism) in post-cystectomy patients. There was a gradual progressive improvement in venogenic competence mechanism in NS cases with insignificant deterioration of arteriogenic mechanism in both groups (NS/NNS).

Traitement de l'incontinence urinaire post-operatoire de l'homme par bandelette sous uretrale: a propos de 16 cas

Objectif: Evaluer les resultats preliminaires de la mise en place d'une bandelette sous uretrale pour le traitement d'incontinence urinaire suite a une chirurgie prostatique chez l'homme selon la technique de Comiter modifiee (sans vissage osseux). Patients et methodes: Entre janvier 2005 et decembre 2006; 16 patients ont ete pris en charge pour incontinence urinaire qui apparut apres chirurgie prostatique. Une bandelette de polypropylene fixee sur le perioste des branches ischio-pubiennes par des fils de nylon et comprimant l'uretre bulbaire a ete mise en place. L'evaluation pre et post-operatoire a ete basee sur l'examen clinique et le nombre de protections utilisees par jour. Les patients ont ete revus a un mois post-operatoire; puis tous les trois mois. Resultats: Avec un recul moyen de 18 mois; 11 patients sont continents ne necessitant pas de protection et 3 patients sont nettement ameliores. Un echec a ete note chez un patient qui avait presente initialement une incontinence severe. Un autre patient a developpe une infection de la bandelette necessitant son retrait et a ete exclus de la serie pour l'evaluation fonctionnelle. Nous n'avons pas constate de douleurs perineales persistantes ni d'erosion uretrale ni d'osteite. Conclusion: Notre modification de la technique selon Comiter semble avoir des resultats satisfaisants comparables avec la technique originale. Elle presente un avantage economique certain par rapport a d'autres kits du marche

[One-stage bilateral rigid ureteroscopy]. / L'urétéroscopie rigide bilatérale au cours de la même séance opératoire.

OBJECTIVE: To evaluate the results of one-stage bilateral rigid ureteroscopy for the treatment of bilateral ureteric stones and to identify predictive factors of failure. MATERIALS AND METHODS: From January 1995 to June 2006, 61 patients were hospitalised for bilateral ureteric stones. Fifty patients, that is, 100 renal units were treated by first-line one-stage bilateral rigid ureteroscopy using an 8 F rigid ureteroscope and a ballistic lithotriptor. A complete statistical analysis (bivariate analysis completed by multivariate analysis) was performed to identify predictive factors of intraoperative failure. RESULTS: The overall success rate per patient (success on at least one side) was 92% (with bilateral success in 70% of cases). Statistical analysis revealed a statistically significant difference between the two failure/success groups for mean stone diameter (p < 0.1%), site (p = 0.6%) and degree of cavity dilatation (p = 4%). Similarly, a strong statistical correlation was observed between these variables and intraoperative failure. The intraoperative complication rate was 4% (two patients) and the postoperative complication rate was 16%, corresponding to minor complications in every case (low back pain, fever) not requiring a supplementary procedure. CONCLUSION: One-stage bilateral rigid ureteroscopy achieved satisfactory results similar to those of unilateral ureteroscopy. Predictive factors of failure were: stone diameter (greater than 15 mm), stones in the lumbar ureter and marked cavity dilatation.

[Intravesical migration of intrauterine device resulting in stone formation]. / Migration intra-vésicale de dispositif intra-utérin compliquée de lithiase.

The migration into the bladder of an intrauterine contraceptive device (IUCD) by uterine perforation is a rare complication. We report two cases of IUCD which migrated into the bladder and subsequently became calcified. The two patients having had their IUCD respectively for 3 and 13 years. Revealing signs were related to bladder irritation for the first patient and hematuria for the second. The diagnosis was suggested on the plain abdominal X-ray and on ultrasound and was confirmed by cystoscopy. Ballistic lithotripsy of the bladder stone with endoscopic extraction of the IUCD was then performed. Performing a transvaginal sonographic examination of the pelvic organs, especially of the uterine anatomy is interesting before insertion of an intrauterine contraceptive device (IUCD), and repeat transvaginal sonographic examinations immediately after the insertion and 4-12 weeks later are advisable. This approach would permit early detection of any complications related to insertion of the IUCD.

A randomized, double-blind comparison between parecoxib sodium and propacetamol for parenteral postoperative analgesia after inguinal hernia repair in adult patients.

The newly injectable cyclooxygenase-2 selective nonsteroidal antiinflammatory drug, parecoxib, has never been compared with propacetamol, a parenteral formulation of acetaminophen. In this prospective, randomized, double-blind, double-dummy study, we randomly assigned 182 patients scheduled for initial inguinal hernia repair under general anesthesia to receive a single injection of 40 mg parecoxib or 2 injections of 2 g propacetamol within the first 12 h after surgery. The study variables were morphine consumption, pain at rest and while coughing, and patient satisfaction throughout the first 12 h postoperatively. For statistical analysis, we used the Student's t-test, chi(2), and covariance analysis. Total morphine consumption did not differ between the two groups. Pain was less intense in the parecoxib group at rest (P = 0.035) but did not differ for pain while coughing. The incidence of side effects was similar. Significantly more patients in the parecoxib group rated their pain management as good or excellent (87% versus 70% in the propacetamol group, P = 0.001). Within the first 12 h after inguinal hernia repair in adult patients, a single injection of parecoxib 40 mg compares favorably with 2 injections of propacetamol 2 g.

Outcome of patients with continent urinary reconstruction and a solitary functioning kidney.

OBJECTIVE: To evaluate the outcome of patients with continent urinary diversions who had a solitary functioning kidney at the time of surgery. PATIENTS AND METHODS: In all, 62 patients with continent urinary reservoirs and a solitary functioning kidney were reviewed (51 men and 11 women). The indications for surgery were bladder cancer in 54 and a contracted bladder in eight. The surgical procedures included an orthotopic ileal neobladder in 36 patients, a continent cutaneous ileal reservoir in 13 and rectal diversion in 13. Kidneys were evaluated using serum creatinine level, ultrasonography, intravenous urography and other radiological studies. RESULTS: The follow-up was 6-173 months; 44 renal units (71%) remained stable during this period. Serum creatinine was increased in four patients with an orthotopic neobladder, with no evidence of obstruction or reflux, in one with preoperative renal impairment and one with voiding dysfunction, reflux and bacteriuria. Six renal units deteriorated because of uretero-intestinal strictures; of these patients, two were treated endoscopically, two with open ureteric reimplantation, one with conversion from a rectal reservoir to an ileal loop conduit, and one was maintained on JJ stenting. Six patients with a rectal diversion had renal deterioration because of chronic pyelonephritis. CONCLUSIONS: A regular follow-up of renal function is mandatory in patients with a continent urinary diversion. Rectal diversion is associated with a higher risk of renal deterioration (54%) than are orthotopic (28%) and cutaneous reservoirs (8%).

[Bladder fibrosis caused by eosinophilic cystitis]. / Fibrose vésicale due à une cystite à éosinophiles.

A 70-years-old man with no history of allergy or genitourinary problems had bilateral hydronephrosis, a marked decrease in bladder capacity and severe eosinophilic infiltration with fibrosis of the bladder wall. A total cystoprostatectomy with ileal bladder replacement was performed. We reviewed the literature of eosinophilic cystitis for clinical presentation, diagnosis and therapeutic options.

The urethral Kock pouch: long-term functional and oncological results in men.

OBJECTIVE: To evaluate our experience with men who underwent radical cystectomy and urethral Kock pouch construction between January 1986 and January 1996. PATIENTS AND METHODS: Complications were classified as early (within the first 3 months after surgery) or late. Continence was assessed by interviewing the patient; they were considered continent if they were completely dry with no need of protection by pads, condom catheter or medication. The patients were followed oncologically and Kaplan-Meier survival curves constructed. Urodynamic studies were used to define the possible causes of enuresis. RESULTS: Three patients died after surgery from pulmonary embolism. There were 67 early complications in 63 patients. The mean (SD) follow-up was 87.8 (49.1) months. There were 111 treatment failures from cancer; of these, four men only had an isolated local recurrence in the urethra. Late complications included 72 pouch stones in 55 patients, and 36 deteriorated renal units caused by reflux (17), uretero-ileal stricture (11), nipple valve eversion (four) or stenosis (four). Interestingly, 65 renal units that were dilated before surgery improved significantly afterward. Ileo-urethral strictures occurred in seven men and anterior urethral strictures in six. Nine patients were totally incontinent and two had chronic urinary retention. Daytime continence was complete in 94% of men, with nocturnal enuresis in 55; the latter had significantly more residual urine, and a higher amplitude and duration of phasic contractions. CONCLUSIONS: Orthotopic bladder substitution after cystectomy for cancer is feasible, with good functional and oncological outcomes in properly selected patients. Nevertheless, the use of a hemi-Kock pouch is associated with many valve-related complications.

Solution structure of Ptu1, a toxin from the assassin bug Peirates turpis that blocks the voltage-sensitive calcium channel N-type.

Ptu1 is a toxin from the assassin bug Peirates turpis which has been demonstrated to bind reversibly the N-type calcium channels and to have lower affinity than the omega-conotoxin MVIIA. We have determined the solution structure of Ptu1 by use of conventional two-dimensional NMR techniques followed by distance-geometry and molecular dynamics. The calculated structure of Ptu1 belongs to the inhibitory cystin knot structural family (ICK) that consists of a compact disulfide-bonded core from which four loops emerge. Analysis of the 25 converged solutions indicates that the molecular structure of Ptu1 contains a 2-stranded antiparallel beta-sheet (residues 24-27 and 31-34) as the only secondary structure. The loop 2 that has been described to be critical for the binding of the toxin on the channel is similar in Ptu1 and MVIIA. In this loop, the critical residue, Tyr13, in MVIIA is retrieved in Ptu1 as Phe13, but the presence of an acidic residue (Asp16) in Ptu1 could disturb the binding of Ptu1 on the channel and could explain the lower affinity of Ptu1 toward the N-type calcium channel compared to the one of MVIIA. Analysis of the electrostatic charge's repartition gives some insights about the importance of the basic residues, which could interact with acidic residues of the channel and then provide a stabilization of the toxin on the channel.

The location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence is not conserved.

Polysaccharide-degrading enzymes are generally modular proteins that contain non-catalytic carbohydrate-binding modules (CBMs), which potentiate the activity of the catalytic module. CBMs have been grouped into sequence-based families, and three-dimensional structural data are available for half of these families. Clostridium thermocellum xylanase 11A is a modular enzyme that contains a CBM from family 6 (CBM6), for which no structural data are available. We have determined the crystal structure of this module to a resolution of 2.1 A. The protein is a beta-sandwich that contains two potential ligand-binding clefts designated cleft A and B. The CBM interacts primarily with xylan, and NMR spectroscopy coupled with site-directed mutagenesis identified cleft A, containing Trp-92, Tyr-34, and Asn-120, as the ligand-binding site. The overall fold of CBM6 is similar to proteins in CBM families 4 and 22, although surprisingly the ligand-binding site in CBM4 and CBM22 is equivalent to cleft B in CBM6. These structural data define a superfamily of CBMs, comprising CBM4, CBM6, and CBM22, and demonstrate that, although CBMs have evolved from a relatively small number of ancestors, the structural elements involved in ligand recognition have been assembled at different locations on the ancestral scaffold.

Chemosensory protein from the moth Mamestra brassicae. Expression and secondary structure from 1H and 15N NMR.

A group of ubiquitous small proteins (average 13 kDa) has been isolated from several sensory organs of a wide range of insect species. They are believed to be involved in chemical communication and perception (olfaction or taste) and have therefore been called chemo-sensory proteins (CSPs). Several CSPs have been identified in the antennae and proboscis of the moth Mamestra brassicae. We have expressed one of the antennal proteins (CSPMbraA6) in large quantities as a soluble recombinant protein in Escherichia coli periplasm. This 112-residue protein is a highly soluble monomer of 13 072 Da with a pI of 5.5. NMR data (1H and 15N) indicate that CSPMbraA6 is well folded and contains seven alpha helices (59 amino acids) and two short extended structures (12 amino acids) from positions 5 to 10 and from 107 to 112. Thirty-seven amino acids are involved in beta turns and coiled segments and four amino acids are not assigned in the NMR spectra (the N-terminus and the residue 52 in the loop 48-53), probably due to their mobility. This is the first report on the expression and structural characterization of a recombinant CSP.

Disulfide bridge reorganization induced by proline mutations in maurotoxin.

Maurotoxin (MTX) is a 34-residue toxin that has been isolated from the venom of the chactidae scorpion Scorpio maurus palmatus, and characterized. Together with Pi1 and HsTx1, MTX belongs to a family of short-chain four-disulfide-bridged scorpion toxins acting on potassium channels. However, contrary to other members of this family, MTX exhibits an uncommon disulfide bridge organization of the type C1-C5, C2-C6, C3-C4 and C7-C8, versus C1-C5, C2-C6, C3-C7 and C4-C8 for both Pi1 and HsTx1. Here, we report that the substitution of MTX proline residues located at positions 12 and/or 20, adjacent to C3 (Cys(13)) and C4 (Cys(19)), results in conventional Pi1- and HsTx1-like arrangement of the half-cystine pairings. In this case, this novel disulfide bridge arrangement is without obvious incidence on the overall three-dimensional structure of the toxin. Pharmacological assays of this structural analog, [A(12),A(20)]MTX, reveal that the blocking activities on Shaker B and rat Kv1.2 channels remain potent whereas the peptide becomes inactive on rat Kv1.3. These data indicate, for the first time, that discrete point mutations in MTX can result in a marked reorganization of the half-cystine pairings, accompanied with a novel pharmacological profile for the analog.

Solution structure of the module X2 1 of unknown function of the cellulosomal scaffolding protein CipC of Clostridium cellulolyticum.

Multidimensional, homo- and heteronuclear magnetic resonance spectroscopy combined with dynamical annealing has been used to determine the structure of a 94 residue module (X2 1) of the scaffolding protein CipC from the anaerobic bacterium Clostridium cellulolyticum. An experimental data set comprising 1647 nuclear Overhauser effect-derived restraints, 105 hydrogen bond restraints and 66 phi torsion angle restraints was used to calculate 20 converging final solutions. The calculated structures have an average rmsd about the mean structure of 0.55(+/-0.11) A for backbone atoms and 1.40(+/-0.11) A for all heavy atoms when fitted over the secondary structural elements. The X2 1 module has an immunoglobulin-like fold with two beta-sheets packed against each other. One sheet contains three strands, the second contains four strands. An additional strand is intercalated between the beta-sandwich, as well as two turns of a 3(.10) helix. X2 1 has a surprising conformational stability and may act as a conformational linker and solubility enhancer within the scaffolding protein. The fold of X2 1 is very similar to that of telokin, titin Ig domain, hemolin D2 domain, twitchin immunoglobulin domain and the first four domains of the IgSF portion of transmembrane cell adhesion molecule. As a consequence, the X2 1 module is the first prokaryotic member assigned to the I set of the immunoglobulin superfamily even though no sequence similarity with any member of this superfamily could be detected.

Maurotoxin versus Pi1/HsTx1 scorpion toxins. Toward new insights in the understanding of their distinct disulfide bridge patterns.

Maurotoxin (MTX) is a scorpion toxin acting on several K(+) channel subtypes. It is a 34-residue peptide cross-linked by four disulfide bridges that are in an "uncommon" arrangement of the type C1-C5, C2-C6, C3-C4, and C7-C8 (versus C1-C5, C2-C6, C3-C7, and C4-C8 for Pi1 or HsTx1, two MTX-related scorpion toxins). We report here that a single mutation in MTX, in either position 15 or 33, resulted in a shift from the MTX toward the Pi1/HsTx1 disulfide bridge pattern. This shift is accompanied by structural and pharmacological changes of the peptide without altering the general alpha/beta scaffold of scorpion toxins.

A new fold in the scorpion toxin family, associated with an activity on a ryanodine-sensitive calcium channel.

We determined the structure in solution by (1)H two-dimensional NMR of Maurocalcine from the venom of Scorpio maurus. This toxin has been demonstrated to be a potent effector of ryanodyne-sensitive calcium channel from skeletal muscles. This is the first description of a scorpion toxin which folds following the Inhibitor Cystine Knot fold (ICK) already described for numerous toxic and inhibitory peptides, as well as for various protease inhibitors. Its three dimensional structure consists of a compact disulfide-bonded core from which emerge loops and the N-terminus. A double-stranded antiparallel beta-sheet comprises residues 20-23 and 30-33. A third extended strand (residues 9-11) is perpendicular to the beta-sheet. Maurocalcine structure mimics the activating segment of the dihydropyridine receptor II-III loop and is therefore potentially useful for dihydropyridine receptor/ryanodine receptor interaction studies. Proteins 2000;40:436-442.