French recommendations for the management of patients with spinal cord injury or at risk of spinal cord injury.

OBJECTIVES: To update the French guidelines on the management of trauma patients with spinal cord injury or suspected spinal cord injury. DESIGN: A consensus committee of 27 experts was formed. A formal conflict-of-interest (COI) policy was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. METHODS: The committee studied twelve questions: (1) What are the indications and arrangements for spinal immobilisation? (2) What are the arrangements for pre-hospital orotracheal intubation? (3) What are the objectives of haemodynamic resuscitation during the lesion assessment, and during the first few days in hospital? (4) What is the best way to manage these patients to improve their long-term prognosis? (5) What is the place of corticosteroid therapy in the initial phase? (6) What are the indications for magnetic resonance imaging in the lesion assessment phase? (7) What is the optimal time for surgical management? (8) What are the best arrangements for orotracheal intubation in the hospital environment? (9) What are the specific conditions for weaning these patients from mechanical ventilation for? (10) What are the procedures for analgesic treatment of these patients? (11) What are the specific arrangements for installing and mobilising these patients? (12) What is the place of early intermittent bladder sampling in these patients? Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® Methodology. RESULTS: The experts' work synthesis and the application of the GRADE method resulted in 19 recommendations. Among the recommendations formalised, 2 have a high level of evidence (GRADE 1+/-) and 12 have a low level of evidence (GRADE 2+/-). For 5 recommendations, the GRADE method could not be applied, resulting in expert advice. After two rounds of scoring and one amendment, strong agreement was reached on all the recommendations. CONCLUSIONS: There was significant agreement among experts on strong recommendations to improve practices for the management of patients with spinal cord injury.

How to perform low-dose computed tomography for renal colic in clinical practice.

Computed tomography (CT) has become the reference technique in medical imaging for renal colic, to diagnose, plan treatment and explore differential diagnosis. Its main limitation is the radiation dose, especially as urinary stone disease tends to relapse and mainly affects young people. It is therefore essential to reduce the CT radiation dose when renal colic is suspected. The goal of this review was twofold. First, we wanted to show how to use low-dose CT in patients with suspected renal colic in current clinical practice. Second, we wished to discuss the different ways of reducing CT radiation dose by considering both behavioral and technological factors. Among the behavioral factors, limiting the scan coverage area is a straightforward and effective way to reduce the dose. Improvement of technological factors relies mainly on using automatic tube current modulation, lowering the tube voltage and current as well using iterative reconstruction.

[Does prenatal diagnosis modify neonatal management and early outcome of children with esophageal atresia type III?]. / Le diagnostic anténatal modifie-t-il la prise en charge néonatale et le devenir à 1 an des enfants suivis pour atrésie de l'œsophage de type III ?

OBJECTIVE: Evaluate neonatal management and outcome of neonates with either a prenatal or a post-natal diagnosis of EA type III. STUDY DESIGN: Population-based study using data from the French National Register for EA from 2008 to 2010. We compared children with prenatal versus post-natal diagnosis in regards to prenatal, maternal and neonatal characteristics. We define a composite variable of morbidity (anastomotic esophageal leaks, recurrent fistula, stenosis) and mortality at 1 year. RESULTS: Four hundred and eight live births with EA type III were recorded with a prenatal diagnosis rate of 18.1%. Transfer after birth was lower in prenatal subset (32.4% versus 81.5%, P<0.001). Delay between birth and first intervention was not significantly different. Defect size (2cm vs 1.4cm, P<0.001), gastrostomy (21.6% versus 8.7%, P<0.001) and length in neonatal unit care were higher in prenatal subset (47.9 days versus 33.6 days, P<0.001). The composite variables were higher in prenatal diagnosis subset (38.7% vs 26.1%, P=0.044). CONCLUSION: Despite the excellent survival rate of EA, cases with antenatal detection have a higher morbidity related to the EA type (longer gap). Even if it does not modify neonatal management and 1-year outcome, prenatal diagnosis allows antenatal parental counseling and avoids post-natal transfer.

The initial management of severe trauma patients at hospital admission.

The initial management of trauma patient is a critical period aiming at: stabilizing the vital functions; following a rigorous injury assessment; defining a therapeutic strategy. This management has to be organized to minimize loss of time that would be deleterious for the patients outcome. Thus, before patient arrival, the trauma team alert should lead to the initiation of care procedures adapted to the announced severity of the patient. Moreover, each individual should know its role in advance and the team should be managed by only one individual (the trauma leader) to avoid conflicts of decision. A rapid trauma injury assessment aims not only at guiding resuscitation (chest drainage, pelvic contention, to define the mean arterial pressure goal) but also to decide a critical intervention in case of hemodynamic instability (laparotomy, thoracotomy, arterial embolisation). This initial assessment includes a chest and a pelvic X-ray, abdominal ultrasound (extended to the lung) and transcranial Doppler (TCD). The whole body scanner with administration of intravenous contrast material is the cornerstone of the injury assessment but can be done for patients stabilized after the initial resuscitation.

[Laparoscopic surgery in children]. / Chirurgie coelioscopique chez l'enfant.

In the last two decades, laparoscopy surgery has been progressively adopted to children. Cardiorespiratory changes induced have been understood and controlled. Abdominal and urological surgery have widely benefited from this technique. Immediate postoperative period is simpler. The risk of small bowel obstruction by bands and adhesions is limited. Nevertheless, laparoscopy is not indicated for all pathologies. In neonatal surgery, more studies are necessary. Maybe the future is robotic surgery.

[Lung separation after reintubation with airway exchange catheter in multiple trauma patient with massive haemoptysis]. / Succès de réintubation avec une sonde à double lumière grâce à un mandrin, lors d'une hémoptysie massive post-traumatique.

A 24-year-old man fell from the third floor. He developed an unilateral pulmonary parenchymal injury and a significant haemoptysis following blunt thoracic trauma. Because of its abundance, it was not possible to obtain adequat oxygenation. To protect controlateral lung from inhalation and to achieve adequat oxygenation, we used double lumen endotracheal tube, lung separation and one lung ventilation. To solve potential airway management difficulties (haemorrhage, trauma, cervical immobilization), we used airway exchange catheter (Cook) to place the double lumen endotracheal tube. Haemoptysis has been controlled by embolization of the right bronchial artery.

[Pneumatic anti-shock garment use leading to non-visualization of pelvic arterial bleeding on angiography]. / Un cas de lésion artérielle pelvienne post-traumatique masquée à l'angiographie par l'emploi d'un pantalon antichoc.

Initial reports of pneumatic anti-shock garment (PASG) in severely hypotensive patients appeared promising. Nevertheless, large-scale studies in prehospital settings have shown no overall reduction in mortality rates among hypotensive patients with application of the PASG. However, in a subsample of patients with blood pressure < or =50 mmHg, PASG seems to be useful to reduce bleeding and improve survival. To our knowledge, our case report is the first which directly showns on angiography the hemostatic effect of PASG on pelvic trauma bleeding. In spite of its possible complications, PASG remains one of the tools of trained trauma teams who regularly treated severe haemorrhagic shock.

[Ascite and head trauma in a child]. / Une ascite chez un enfant victime d'un traumatisme crânien.

We report the case of an 11 months old boy who felt from 3 m high. He had an isolated brain injury with contusion and bleeding in the right frontal lobe. A large ascite was discovered in the Intensive Care Unit 6 days after the trauma. The CT scan did not reveal any abdominal lesion. This peritoneal fluid was transudative ascitic fluid which appeared to be mediated by beta-sympathetic hyperactivity of central origin. Sequential echography showed progressive improvement and disappearance of the ascite on 19th day post trauma.

Preoperative coagulation tests in former preterm infants undergoing spinal anaesthesia.

BACKGROUND: Clinical history is insufficient to detect disorders of haemostasis in infants aged less than 1 year and laboratory coagulation testing is recommended in infants before perimedullar anaesthesia. METHODS: We designed a retrospective study to assess the preoperative coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time, platelet count] performed in 141 former preterm infants who underwent spinal anaesthesia for elective inguinal hernia repair. All the infants had recovered from any significant medical event (necrotizing enterocolitis, intracranial haemorrhages, transfusions of blood products, sepsis, etc.) when they were scheduled for surgery. RESULTS: Mean values for aPTT were frequently abnormal (60.4%) in infants with a postconceptional age of less than 45 weeks. No complication related to the puncture or abnormal perioperative bleeding was detected. CONCLUSIONS: Other coagulation tests should be evaluated to assess the coagulation status in infants with a postconceptional age of less than 45 weeks.

[Evaluation of antibacterial filters for peridural obstetrical anesthesia]. / Evaluation des filtres antibactériens utilisés pour l'analgésie péridurale obstétricale.

OBJECTIVES: To assess the antibacterial efficiency of filters used in obstetrics when epidural top-ups are performed. STUDY DESIGN: Observational prospective study. PATIENTS AND METHODS: We aseptically collected 201 antibacterial filters that had been used for top-ups with ropivacaine +/- sufentanil for epidural analgesia during labour. We flushed them first with 2 mL of saline and then with 2 mL of a solution containing 1.5 x 10(6) Staphylococcus epidermidis/mL. The filtrates were incubated at 37 degrees C for 72 h. Number of top-ups and duration of epidural analgesia are expressed as median (extremes). RESULTS: 3 (1-10) top-ups were performed for labour analgesia over a period of 6.5 h (1.8-18). After filtering, all the solutions were found to be sterile. Especially, when using Staphylococcus epidermidis solutions, bacteria were not found beyond any filter. These results suggest the integrity of the filter membrane after several boluses. No infection related to epidural analgesia was reported. CONCLUSION: Antibacterial filters provide a good protection against a potentially contaminated procedure during epidural top-ups.

Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products.

Proteasomes are the main proteases responsible for cytosolic protein degradation and the production of major histocompatibility complex class I ligands. Incorporation of the interferon gamma--inducible subunits low molecular weight protein (LMP)-2, LMP-7, and multicatalytic endopeptidase complex--like (MECL)-1 leads to the formation of immunoproteasomes which have been associated with more efficient class I antigen processing. Although differences in cleavage specificities of constitutive and immunoproteasomes have been observed frequently, cleavage motifs have not been described previously. We now report that cells expressing immunoproteasomes display a different peptide repertoire changing the overall cytotoxic T cell--specificity as indicated by the observation that LMP-7(-/-) mice react against cells of LMP-7 wild-type mice. Moreover, using the 436 amino acid protein enolase-1 as an unmodified model substrate in combination with a quantitative approach, we analyzed a large collection of peptides generated by either set of proteasomes. Inspection of the amino acids flanking proteasomal cleavage sites allowed the description of two different cleavage motifs. These motifs finally explain recent findings describing differential processing of epitopes by constitutive and immunoproteasomes and are important to the understanding of peripheral T cell tolerization/activation as well as for effective vaccine development.

Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide.

Tumor necrosis factor (TNF)-alpha increases mitochondrial reactive oxygen species (ROS) production in tumor cells and hepatocytes. However, whether TNF-alpha stimulates mitochondrial ROS production in endothelial cells (EC) has not yet been reported. We studied the effect of TNF-alpha on mitochondrial ROS generation in EC and the signaling pathways involved. Cultured human umbilical vein EC (HUVEC) were studied by fluorescence microscopy, using dichlorodihydrofluorescein diacetate (DCFH-DA) as a marker of ROS production and propidium iodide uptake for cell viability. TNF-alpha increased DCFH oxidation in HUVEC dose-dependently. To determine the source of ROS, the mitochondrial respiratory chain inhibitors rotenone + thenoyltrifluoroacetone (TTFA), which inhibit electron entry to ubiquinone, and antimycin A (AA), a blocker of ubisemiquinone, were used. Rotenone and TTFA inhibited (n = 7, P < 0.05), whereas AA increased (118% in 3 min; n = 4, P < 0.01) ROS generation in HUVEC. In contrast, ROS production was not abolished by the nicotinamide adenine dinucleotide phosphate-dependent oxidase inhibitor diphenylene iodonium, by the xanthine oxidase inhibitor allopurinol, nor by the nitric oxide and cyclooxygenase pathway inhibitors N(omega)-nitro-L-arginine and mefenamic acid. In addition, TNF-alpha-induced ROS production was inhibited by the acidic sphingomyelinase inhibitor desipramine (5 microM; -80%, n = 4, P < 0.01) and totally blocked by the ceramide-activated protein kinase (CAPK) inhibitor dimethylaminopurine (1 mM; n = 6, P < 0.05). Thus, TNF-alpha induces mitochondrial ROS production in HUVEC that primarily occurs at the ubisemiquinone site and is mediated by ceramide-dependent signaling pathways involving CAPK.

Vaginal hysterectomy for enlarged uteri, with or without laparoscopic assistance: randomized study.

OBJECTIVE: To compare short-term results of vaginal hysterectomy (VH) with those of laparoscopically assisted vaginal hysterectomy (LAVH) in women with enlarged uteri. METHODS: Eighty women referred for abdominal hysterectomies for benign disease were assigned randomly to vaginal hysterectomy or LAVH. Inclusion criteria were uterine size larger than 280 g and one or more of the following traditional contraindications of vaginal hysterectomy: previous pelvic surgery, history of pelvic inflammatory disease, moderate or severe endometriosis, concomitant adnexal masses, indication for adnexectomy, and nulliparity without uterine descent. RESULTS: There were no differences in patients' mean age, parity, rate of postmenopausal state, previous pelvic surgery, preoperative hemoglobin levels, and mean uterine weight. Indications for surgery were similar between groups. No difference was found in the mean +/- standard deviation (SD) uterine weight (range) between vaginal hysterectomy and LAVH groups (424 +/- 211 g [280--930 g] and 513 +/- 360 g [290--1560 g]), respectively. Except for one bladder injury in the laparoscopic group (injury treated laparoscopically), there were no other major complications. Complication rates in vaginal and laparoscopic groups were 15% and 37.5%, respectively (P <.05). Mean operating time was shorter in the vaginal than the laparoscopic group (108 +/- 35 minutes and 156 +/- 50 minutes, respectively [P <.001]). There was no difference in first day hemoglobin level drops or hospital stays between groups. CONCLUSION: Vaginal hysterectomy can be successful even in women with enlarged uteri and other conditions considered by some to contraindicate the operation. Laparoscopically assisted vaginal hysterectomy offered no advantages over the standard vaginal hysterectomy.

Tissue-specific and ubiquitous promoters direct the expression of alternatively spliced transcripts from the calcitonin receptor gene.

The gene encoding the murine calcitonin receptor (mCTR) was isolated, and the exon/intron structure was determined. Analysis of transcripts revealed novel cDNA sequences, new alternative exon splicing in the 5'-untranslated region, and three putative promoters (P1, P2, and P3). The longest transcription unit is greater than 67 kilobase pairs, and the location of introns within the coding region of the mCTR gene (exons E3-E14) are identical to those of the porcine and human CTR genes. We have identified novel cDNA sequences that form three new exons as well as others that add 512 base pairs to the 5' side of the previously published cDNA, thereby extending exon E1 to 682 base pairs. Two of these novel exons are upstream of exon E2 and form a tripartite exon E2 (E2a, E2b, and E2c) in which E2a is utilized by promoter P2 with variable splicing of E2b. The third new exon (E3b') lies between E3a and E3b and is utilized by promoter P3. Analysis of mCTR mRNAs has revealed that the three alternative promoters give rise to at least seven mCTR isoforms in the 5' region of the gene and generate 5'-untranslated regions of very different lengths. Analysis by reverse transcription-polymerase chain reaction shows that promoters P1 and P2 are utilized in osteoclasts, brain, and kidney, whereas promoter P3 appears to be osteoclast-specific. Using transiently transfected reporter constructs, promoter P2 has activity in both a murine kidney cell line (MDCT209) and a chicken osteoclast-like cell line (HD-11EM), whereas promoter P3 is active only in the osteoclast-like cell line. These transfection data confirm the osteoclast specificity of promoter P3 and provide the first evidence that the CTR gene is regulated in a tissue-specific manner by alternative promoter utilization.

Results of recto-vaginal fistula repair: retrospective analysis of 48 cases.

OBJECTIVE: To evaluate the long-term outcome of the Musset technique of recto-vaginal fistula (RVF) repair. STUDY DESIGN: During the years 1992-1998, 48 women underwent recto-vaginal fistula repair. A retrospective study in a university tertiary referral center was conducted. RESULTS: The main etiologies were obstetrical trauma (25), local infection (11), inflammatory disease (7), and post surgery (3). Thirty women (63%) had a previous fistula repair failure. The mean+/-S.D. fistula diameter was 1.4+/-1.0, and in 40% of the patients the fistula diameter was >2.5cm. In 19 cases (39.6%) there was a complete opening of the perineum and anal sphincter. Gas and stool incontinence before the operation were noted in 85 and 75% of the patients, respectively. Successful anatomic results were achieved in all patients. Five patients were re-operated due to gas and stool incontinence, and all but one had satisfactory anatomic and functional satisfactory results. The success rates in women with Crohn's disease and with a previous RVF repair failure were 100 and 98%, respectively. No major intra or postoperative complications were noted. CONCLUSION: The Musset procedure provide excellent anatomic and functional results and women with Crohn's disease or previous RVF repair have comparable long-term results.

[Hormone replacement therapy after endometrial or ovarian cancer]. / Traitement hormonal substitutif après cancer de l'endomètre ou de l'ovaire.

Use of hormonal replacement therapy after treatment of ovarian or endometrial cancer remains a matter of debate. Novel adjuvant therapies tend to increase the survival of these patients, who are exposed to risk factors of hormonal deficiency subsequent to primary therapy. Therefore, the aims of the present review of literature was to analyse epidemiologic and clinical parameters on behalf on hormonal replacement therapy in this population.

T cell receptor gamma gene regulatory sequences prevent the function of a novel TCRgamma/pTalpha pre-T cell receptor.

Expression of a TCRgamma transgene in RAG-1-/- mice resulted in the development of a limited number of CD4+CD8+ (DP) thymocytes. In vivo treatments with anti-TCRgamma antibody enhanced the number of DP thymocytes, demonstrating that TCRgamma chains were expressed on the cell surface in the absence of delta, alpha, or beta chains. Mutations in pTalpha or CD3epsilon genes abolished transgene-induced DP cell development, indicating that TCRgamma can associate with pTalpha and CD3 to form a novel pre-TCR. With a transgene containing additional regulatory sequences, TCRgamma expression was down-regulated in DP cells, and little DP cell development occurred. Thus, the function of the endogenous TCRgamma/pTalpha is limited by the transcriptional down-regulation of TCRgamma genes that normally accompanies DP cell development.

Restoration of thymopoiesis in pT alpha-/- mice by anti-CD3epsilon antibody treatment or with transgenes encoding activated Lck or tailless pT alpha.

Mice deficient for the pre-TCR alpha (pT alpha) chain cannot form a pre-T cell receptor (TCR) and exhibit a severe defect in early T cell development, characterized by lack of "beta selection" and impaired generation of double-positive (DP) thymocytes. Here, we demonstrate that intraperitoneal injection of CD3epsilon-specific antibodies into pT alpha-/- x RAG-/- mice or introduction of an activated p56(lck) transgene in pT alpha-/- mice fully restores the number of DP thymocytes, and that expression of a transgenic pT alpha chain lacking its cytoplasmic portion can overcome all developmental defects associated with pT alpha deficiency. These results allow a better definition of the role of pT alpha in pre-TCR signal transduction and provide conclusive evidence that the cytoplasmic tail of pT alpha is not essential for pre-TCR signaling.

Genomic structure and chromosomal location of the mouse pre-T-cell receptor alpha gene.

The mouse pre-T-cell receptor alpha (pT alpha) chain is a 33,000 M(r) glycoprotein expressed on the surface of immature thymocytes as a disulfide-linked heterodimer with the T-cell receptor beta (TCR beta) chain, and in association with proteins of the CD3 complex. The cDNA for pT alpha, isolated previously, encodes a type I transmembrane protein that is a member of the immunoglobulin (Ig) superfamily. Here we report the complete nucleotide sequence, the exon/intron structure, and the chromosomal location of the pTa gene. The gene spans about 8.4 kilobases (kb) and consists of four exons. Exon 1 encodes the 5' untranslated region, the leader peptide, and the first three amino acids of the mature protein. This exon is followed by a relatively long intron of 4.9 kb that contains many short interspersed repeats (SINEs) of the B1 and B2 family. The second exon encodes the extracellular Ig-like domain and exon 3 with just 45 base pairs the connecting peptide (CP), including the cysteine required for heterodimer formation. A similar exon/intron structure encoding corresponding parts of the mature polypeptide is found both in the Tcra and Tcrd constant region genes. The last exon encodes the transmembrane portion, the cytoplasmic tail, and about 540 nucleotides of 3' untranslated sequence, including a B2 repetitive element. In situ hybridization maps the pTa gene to the D/E1 region of mouse chromosome 17.