[Evidence-based ways of colorectal anastomotic complications prevention in the setting of digestive deep endometriosis resection: CNGOF-HAS Endometriosis Guidelines]. / Moyens de prévention des complications anastomotiques digestives dans la chirurgie de l'endométriose profonde, RPC Endométriose CNGOF-HAS.

Management of deep pelvic and digestive endometriosis can lead to colorectal resection and anastomosis. Colorectal anastomosis carries risks for dreaded infectious and functional morbidity. The aim of the study was to establish, regarding the published data, the role of the three most common used surgical techniques to prevent such complications: pelvic drainage, diverting stoma, epiplooplasty. Even if many studies and articles have focused on colorectal anastomotic leakage prevention in rectal cancer surgery data regarding this topic in the setting of endometriosis where lacking. Due to major differences between the two situations, patients, diseases the use of the conclusions from the literature have to be taken with caution. In 4 randomized controlled trials the usefulness of systematic postoperative pelvic drainage hasn't been demonstrated. As this practice is not systematically recommended in cancer surgery, its interest is not demonstrated after colorectal resection for endometriosis. There is a heavy existing literature supporting systematic diverting stoma creation after low colorectal anastomosis for rectal cancer. Keeping in mind the important differences between the two situations, the conclusions cannot be directly extrapolated. In endometriosis surgery after low rectal resection, stoma creation must be discussed and the patient must be informed and educated about this possibility. Even if widely used there is no data supporting the role of epiplooplasty in colorectal anastomotic complication prevention? The place for epiplooplasty in preventing rectovaginal fistula occurrence in case of concomitant resection hasn't been studied.

Folliculotropic T-cell infiltrates associated with B-cell chronic lymphocytic leukaemia or MALT lymphoma may reveal either true mycosis fungoides or pseudolymphomatous reaction: seven cases and review of the literature.

BACKGROUND: Mycosis fungoides (MF) and pseudo-MF (or MF simulant) can be associated with B-cell malignancies, but distinction between a true neoplasm and a reactive process may be difficult. OBJECTIVES: To report seven patients with B-cell malignancy and folliculotropic MF or pseudo-MF and emphasize on criteria allowing distinction between the two conditions. METHODS: We retrospectively and prospectively included seven patients with B-cell malignancy who presented skin lesions histologically consisting in a folliculotropic T-cell infiltrate and reviewed the literature on the topic. RESULTS: Four men and three women had a chronic lymphocytic leukaemia (n = 6) or a MALT-type lymphoma (n = 1). Five patients had localized papules, and two had patches and plaques. Histological examination showed in all cases a diffuse dermal T-cell infiltrate with folliculotropic involvement and follicular mucinosis associated with clusters of the B-cell lymphoma, without significant expression of follicular helper T-cell markers. T-cell rearrangement studies showed a polyclonal pattern in the patients with papules and a monoclonal pattern in the cases of patches and plaques. Papular lesions had an indolent evolution, whereas patches and plaques persisted or worsened into transformed MF. CONCLUSION: Folliculotropic T-cell infiltrates associated with B-cell malignancies can be either a true folliculotropic MF or a pseudo-MF. The distinction between both conditions cannot rely only on the histopathological aspect, but needs both a clinical pathological correlation and the search for a dominant T-cell clone. Whether the neoplastic T and B cells derive from a common ancestor or the T-cell proliferation is promoted by the underlying B-cell lymphoma remains unsolved, but interaction between B and T cell in the skin does not appear to be dependent on a TFH differentiation of the T-cell infiltrate.

[Transvaginal hydrolaparoscopy for infertility investigation: a retrospective study, about 262 patients]. / Intérêt de la fertiloscopie dans la prise en charge de l'infertilité: étude rétrospective, à propos de 262 cas.

OBJECTIVES: To evaluate fertiloscopy's results and to redefine its place in the management of female infertility. PATIENTS AND METHODS: Retrospective study including 262 cases of fertiloscopy and 260 patients with primary or secondary idiopathic infertility. Analysis of infertility assessment's findings (hysterosalpingography), perioperative data (operating technique, laparoscopic conversion, failures and complications). Comparison of hysterosalpingography's findings and peroperative data; comparison of fertiloscopy and laparoscopy's findings. RESULTS: Access to peritoneal cavity was possible for 248 fertiloscopies (95%), and pelvic exploration was considered as complete for 226 cases (86%). Laparoscopic conversion was necessary in 54 cases (21%) and indicated by surgical pathology in more of one third of the cases (n=20). Our failure rate was only 5,3% (n=14), partially thanks to posterior colpotomie (70% of failures avoided). We deplored 8 complications (3.05%) which were not severe (no bowel injury), among which half were linked with the hysteroscopy (uterus perforation). In the cases of laparoscopic conversion, laparoscopic findings confirmed per-fertiloscopic data, considering adhesions and tubal patency. Hysterosalpingography had poor sensibility and positive predictive value. DISCUSSION AND CONCLUSION: Fertiloscopy is a safe, reproducible and not much invasive procedure. It can be substituted to laparoscopy in infertility assessment when there is no obvious surgical indication. Moreover, it could be considered as a first line way of investigation in female infertility management, instead of hysterosalpingography which has poor sensibility and positive predictive value.

Mutations in NOTCH2 in patients with Hajdu-Cheney syndrome.

UNLABELLED: The Hajdu-Cheney syndrome is a very rare disease that affects several organ system, leading to severe osteoporosis and other abnormalities. We describe clinical and genetic findings of nine patients with this disease. INTRODUCTION: The Hajdu-Cheney syndrome (HCS) is a rare autosomal dominant disorder characterized by severe osteoporosis, acroosteolysis of the distal phalanges, renal cysts, and other abnormalities. Recently, heterozygous mutations in NOTCH2 were identified as the cause of HCS. METHODS: Nine patients with typical presentations of HCS took part in this study: five affected patients from two small families and four sporadic cases. Peripheral blood DNA was obtained and exome sequencing performed in one affected individual per family and in all four sporadic cases. Sanger sequencing confirmed mutations in all patients. RESULTS: One of the identified mutations was introduced in a plasmid encoding NOTCH2. Wild-type and mutant NOTCH2 were transiently expressed in HEK293 cells to assess intracellular localization after ligand activation. Deleterious heterozygous mutations in the last NOTCH2 exon were identified in all patients; five of the six mutations were novel. CONCLUSION: Consistent with previous reports, all mutations are predicted to result in a loss of the proline/glutamic acid/serine/threonine sequence, which harbors signals for degradation, therefore suggesting activating mutations. One of the six mutations furthermore predicted disruption of the second nuclear localization signal of NOTCH2, but the mutant revealed normal nuclear localization after transfection, which is consistent with the proposed gain-of-function mechanism as the cause of this autosomal dominant disease. Our findings confirm that heterozygous NOTCH2 mutations are the cause of HCS and expand the mutational spectrum of this disorder.

[Postoperative imaging of the pancreas and duodenum]. / Imagerie post-opératoire du pancréas et du duodénum.

Pancreatic surgery is a frequent therapeutic approach for benign and malignant conditions. CT has become the imaging method of reference to detect early postoperative complications and to detect recurrent disease during long-term follow-up. Knowledge of the normal postoperative anatomy is essential for accurate interpretation of CT scans. The purpose of this paper is to illustrate the normal and abnormal CT appearances of common surgical procedures involving the pancreas.

[Congenital transient leukemia: a case report]. / Un cas de leucémie congénitale transitoire.

UNLABELLED: Neonates with Down's syndrome have an increased risk for congenital leukaemia, particularly acute megakaryoblastic leukaemia (FAB, M7) which most often resolves spontaneously and is called transient leukaemia. It can be observed in non-constitutional trisomy 21 infants then presenting trisomy 21 on blasts cells. OBSERVATION: We report a transient leukaemia with an isolated pericardial effusion in a phenotypically normal neonate. Trisomy 21 was found on blasts cells. Complete remission remains after 32 months. DISCUSSION: Congenital leukaemias, with trisomy 21 on blasts cells have a good prognosis that justifies observation before using chemotherapy.

[Imaging of a thickened-wall gallbladder]. / Imagerie des épaississements de la paroi vésiculaire.

Thickening of the gallbladder wall may result from a large spectrum of pathological conditions, intrinsic as well as extrinsic to the biliary tract, and may have different appearances. Accurate diagnosis is usually established after a correlation of imaging findings, laboratory data and clinical history. US remains the initial imaging modality for the evaluation of acute right upper quadrant pain. CT and MRI are complementary to US and have an increasing role in assessing a thickened-wall gallbladder.

Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein following focal cerebral ischemia in rats.

Hypoxia is a common cause of cell death and is implicated in many disease processes including stroke and chronic degenerative disorders. In response to hypoxia, cells express a variety of genes which allow adaptation to altered metabolic demands, decreased oxygen demands, and the removal of irreversibly damaged cells. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in cells. In this study, we reported an early, time-related, gradual up-regulation of HIF-1alpha, and a moderate increase in vascular endothelial growth factor (VEGF)- and erythropoietin (Epo)-levels following transient focal ischemia. Moreover, we demonstrated, for the first time a specific localization of the pro-apoptotic regulator BNIP3 in striatal and cortical neurons after transient focal ischemia in rats. Prolonged intranuclear BNIP3 immunoreactivity was associated with delayed neuronal death. Experiments showed protein increases on Western blots of brain tissue with peaks at 48h after ischemia. Epo responds to ischemia in an early stage, whereas VEGF and BNIP3 accumulate in cells at later times after ischemia. This suggests the possibility that BH3-only proteins might be one of the major downstream effectors of HIF-1alpha in hypoxic cell death. These findings open the possibility that the hypoxia-regulated pro-apoptotic protein BNIP3 enters the nucleus and could interact with other proteins involved in DNA structure, transcription or mRNA splicing after focal brain ischemia.

[Imaging of pancreatic adenocarcinoma]. / Imagerie de l'adénocarcinome du pancréas.

Pancreatic cancer remains the fourth most common cause of cancer death. Surgery remains the only option for cure. Accurate diagnosis and staging are essential for appropriate management of patients with pancreatic cancer. This paper reviews the state of the art for imaging modalities in the diagnosis and staging of pancreatic adenocarcinoma. The crucial role of CT has increased with the new generation of multidetector CT.

Angiopoietin-1-induced PI3-kinase activation prevents neuronal apoptosis.

Although angiopoietin-1 (Ang-1) is recognized as an endothelial growth factor, its presence in brain following an ischemic event suggests a role in the evolution of neuronal damage. Using primary neuronal cultures, we showed that neurons express Ang-1 and possess the functional angiopoietin-receptor Tie-2, which is phosphorylated in the presence of Ang-1. We further investigated in vitro whether Ang-1 could protect neurons against either excitotoxic necrosis or apoptosis induced by serum deprivation (SD). A neuroprotective effect for Ang-1 was detected exclusively in the apoptotic paradigm. Treatment of cells with the phosphatidyl-inositol 3-kinase (PI3-K) inhibitor, LY294002, inhibited Ang-1-induced phosphorylation of Akt, restored the cleavage of the effector caspase-3, and reduced the protective effect of Ang-1 against SD-induced toxicity. These findings suggest that Ang-1 has a neuroprotective effect against apoptotic stress and that this effect is dependent on the PI3-K/Akt pathway and inhibition of caspase-3 cleavage. This study provides evidence that Ang-1 is not just angiogenic but also neuroprotective. The understanding of neuroprotective mechanisms induced by Ang-1 may promote strategies based on the pleiotropic effects of angiogenic factors. Such approaches could be useful for the treatment of brain diseases in which both neuronal death and angiogenesis are involved.

Diagnostico de desnutricion y de riesgo de desnutricion en un hospital general de adultos / Diagnosis of malnutrition and risk of malnutrition in general hospital of adults

Antecedentes: hasta el momento, se desconoce la prevalencia de la desnutrición y del riesgo de la desnutrición en los pacientes internados en los hospitales generales de adultos del pais. Sólo existen informes parciales sobre desnutrición en afecciones médicas y en pacientes neoplásicos con y sin metástasis. Objetivos Conocer la prevalencia de la desnutrición y de riesgo de la desnutrición en pacientes internados en un hospital genera] de adultos (Hospital Pasteur, Montevideo, Uruguay) excluidas las áreas de medicina intensiva. 2. Determinar la constancia del diagnóstico nutricional en las historias clínicas de los pacientes. Material y métodos Encuesta sobre el estado nutricional de 179 pacientes internados en áreas médico-quirúrgicas no críticas del hospital, utilizando una Escala de Categorización Mutricional basada en la valoración global subjetiva (VGS) (A = bien nutridos; B = En riesgo de desnutrición; C= Desnutrición moderada; D = Desnutrición severa), cotejando su rendimiento con el índice de masa corporal (IMC) y la auditoría de las historias clínicas de los mismos pacientes, para determinar la constancia del diagnóstico nutricional y de peso-talla en las mismas. Resultados De los 179 pacientes encuestados, y de acuerdo a la escala propuesta, 39 (25 en C; 14 en D) estaban desnutridos (21.5 por ciento) y 37 (21 por ciento) estaban en riesgo de desnutrición (B). El IMC correspondiente a C y D es, de modo muy significativo, menor que el de A (p < 0.001). Sin embargo, A no es significativamente diferente de B, ni C lo es deD. En las 179 historias clínicas auditadas, sólo 24 (13.4 por ciento) tenían constancia del diagnóstico nutricional y ninguna presentó, en forma conjunta, los datos de peso y talla. Conclusiones Existe una alta prevalencia de desnutrición moderada-severa y de riesgo de desnutrición en la población hospitalaria encuestada, según la escala utilizada. Ésta se demostró más adecuada que el IMC per se para la categorización nutricional. Éste último no discrimina entre A y B ni entre C y D. Además, el IMC se altera en presencia de edemas y/o ascitis...

A possible role of the Na(+)/K(+)-ATPase for O(2) production from H(2)O(2).

We are attempting to supply a new insight on interaction between Na(+)/K(+)-ATPase and H(2)O(2). We demonstrate that in vitro the Na(+)/K(+)-ATPase, a non heme-protein, is able to disproportionate H(2)O(2) catalatically into dioxygen and water, as well as C(40) catalase. By polarography, we quantify O(2) production and by Raman spectroscopy H(2)O(2) consumption. A comparative analysis of kinetics parameters relative to O(2) production shows that for Na(+)/K(+)-ATPase the affinity of the catalytic site able to transform H(2)O(2) into O(2) is twice weaker than that for C(40) catalase. It also shows that the molar activity for O(2) production is 300-fold weaker for ATPase than for catalase. Inhibitors, pH and GSH studies highlight the differences between the heme- and nonheme-proteins. Indeed, for C(40), NaN(3) is strongly inhibiting, but much less for ATPase. The pH range for the catalatic activity of ATPase is wide (6.5 to 8.5), while it is not for C(40) catalase (optimum at pH 8). The Na(+)/K(+)-ATPase catalatic activity is reduced in presence of glutathione, while it is not the case with C(40) catalase.

[Meningeal metastases of ovarian cancer. Contribution of imaging]. / Métastases méningées du cancer de l'ovaire. Apport de l'imagerie.

BACKGROUND: Secondary meningeal localizations are uncommon and may disclose reactivation of a malignant disease. Most meningeal metastases occur in breast cancer, exceptionally in primary ovarian cancer. CASE REPORT: We report 2 cases of secondary meningeal localizations of ovarian cancer. The diagnosis was clinical, supported by cerebrospinal fluid analysis and computed tomography and magnetic resonance imaging. DISCUSSION: Establishing the diagnosis of carcinomatous meningitis may be difficult. Clinical signs and biological data are not always conclusive. If spinal tap is contraindicated or negative, imaging, particularly magnetic resonance imaging is highly contributive in establishing the diagnosis of secondary localization. A precise evaluation of the invaded tissues is quite helpful in guiding therapeutic management based on chemotherapy, tumor resection or radiotherapy.

Neurons and astrocytes express EPO mRNA: oxygen-sensing mechanisms that involve the redox-state of the brain.

Erythropoietin (Epo), the major hormone controlling the hypoxia-induced increase in the number of erythrocytes, has also a functional role in the brain. However, few data exist as to the cellular source of brain-derived Epo as well as to the molecular mechanisms that control Epo expression in the central nervous system. Using patch-clamp and RT-PCR methods, we provide direct evidence that, besides astrocytes, neurons are a source of Epo in the brain. Both the astrocytic and neuronal expression of Epo mRNA are induced not only by hypoxia, but also by desferrioxamine (DFX) and cobalt chloride (CoCl(2)), two agents known to mimic the hypoxic induction of Epo in hepatoma cells. This induction is blocked by cycloheximide suggesting that de novo protein synthesis is required. Furthermore, the addition of H(2)O(2) decreases the hypoxia-induced Epo mRNA levels. These data indicate that, following hypoxia, a common oxygen sensing and signaling pathway leads to increased Epo gene expression in both nervous and hepatoma cells; this pathway would be dependent on the redox-state of the brain. Furthermore, we show that the in vivo administration of CoCl(2) and DFX to mice induces an increased Epo mRNA level in the neocortex. As Epo protects the brain against ischemia, our in vivo experiments suggest that the use of molecules such as CoCl(2) or DFX, that provoke an increased Epo gene expression in the brain, could be useful in the development of potential therapeutic strategies for the treatment of hypoxic or ischemic brain injury.

Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia.

We investigated the hypothesis that hypoxia induces angiogenesis and thereby may counteract the detrimental neurological effects associated with stroke. Forty-eight to seventy-two hours after permanent middle cerebral artery occlusion we found a strong increase in the number of newly formed vessels at the border of the infarction. Using the hypoxia marker nitroimidazole EF5, we detected hypoxic cells in the ischemic border of the neocortex. Expression of vascular endothelial growth factor (VEGF), which is the main regulator of angiogenesis and is inducible by hypoxia, was strongly up-regulated in the ischemic border, at times between 6 and 24 hours after occlusion. In addition, both VEGF receptors (VEGFRs) were up-regulated at the border after 48 hours and later in the ischemic core. Finally, the two transcription factors, hypoxia-inducible factor-1 (HIF-1) and HIF-2, known to be involved in the regulation of VEGF and VEGFR gene expression, were increased in the ischemic border after 72 hours, suggesting a regulatory function for these factors. These results strongly suggest that the VEGF/VEGFR system, induced by hypoxia, leads to the growth of new vessels after cerebral ischemia. Exogenous support of this natural protective mechanism might lead to enhanced survival after stroke.

Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation.

We have characterized 21 mutations in the type VII collagen gene (COL7A1) encoding the anchoring fibrils, 18 of which were not previously reported, in patients from 15 unrelated families with recessive dystrophic epidermolysis bullosa (RDEB). COL7A1 mutations in both alleles were identified by screening the 118 exons of COL7A1 and flanking intron regions. Fourteen mutations created premature termination codons (PTCs) and consisted of nonsense mutations, small insertions, deletions, and splice-site mutations. A further seven mutations predicted glycine or arginine substitutions in the collagenous domain of the molecule. Two mutations were found in more than one family reported in this study, and six of the seven missense mutations showed clustering within exons 72-74 next to the hinge region of the protein. Patients who were homozygous or compound heterozygotes for mutations leading to PTCs displayed both absence or drastic reduction of COL7A1 transcripts and undetectable type VII collagen protein in skin. In contrast, missense mutations were associated with clearly detectable COL7A1 transcripts and with normal or reduced expression of type VII collagen protein at the dermo/epidermal junction. Our results provide evidence for at least two distinct molecular mechanisms underlying defective anchoring fibril formation in RDEB: one involving PTCs leading to mRNA instability and absence of protein synthesis, the other implicating missense mutations resulting in the synthesis of type VII collagen polypeptide with decreased stability and/or altered function. Genotype-phenotype correlations suggested that the nature and location of these mutations are important determinants of the disease phenotype and showed evidence for interfamilial phenotypic variability.

Three novel point mutations in the keratinocyte transglutaminase (TGK) gene in lamellar ichthyosis: significance for mutant transcript level, TGK immunodetection and activity.

We have investigated 8 patients from 7 unrelated families with lamellar ichthyosis (LI) for defects in the keratinocyte transglutaminase (TGK) gene. We have characterized three novel homozygous mutations and a previously reported splice acceptor site mutation. One patient showed a C-to-T change in the binding site for the transcription factor Sp1 within the promoter region. Another patient had a Gly 143-to-Glu mutation in exon 3 and a third patient, affected with a particular form of LI sparing the four limbs, demonstrated a Val382-to-Met mutation within exon 7. These three patients exhibited drastically reduced transglutaminase activity and an absence of detectable TGK polypeptide, as assessed by immunofluorescence and immunoblotting. Northern blot analysis showed that the Sp1 site mutation was associated with profound reduction of TGK transcript levels whereas normal transcript levels were observed for the two missense mutations. We hypothesize that the Sp1 site mutation impairs transcription of the TGK gene, whereas the two missense mutations induce structural changes leading to protein instability. Linkage to TGK was excluded in another family and no evidence for TGK defect was found in 3 other patients. These results further support the involvement of TGK in some patients with LI. They identify a TGK mutation as a cause for non-generalized LI and further delineate the molecular mechanisms underlying TGK deficiency in LI.