Ten candidate ADAMTS13 mutations in six French families with congenital thrombotic thrombocytopenic purpura (Upshaw–Schulman syndrome)

Summary.  ADAMTS13, the specific von Willebrand factor (VWF)-cleaving metalloprotease, prevents the spontaneous formation of platelet thrombi in the microcirculation by degrading the highly adhesive ultralarge VWF multimers into smaller forms. ADAMTS13 severe enzymatic deficiency and mutations have been described in the congenital thrombotic thrombocytopenic purpura (TTP or Upshaw–Schulman syndrome), a rare and severe disease related to multivisceral microvascular thrombosis. We investigated six French families with congenital TTP for ADAMTS13 enzymatic activity and gene mutations. Six probands with congenital TTP and their family were tested for ADAMTS13 activity in plasma using a two-site immunoradiometric assay and for ADAMTS13 gene mutations using polymerase chain reaction and sequencing. ADAMTS13 activity was severely deficient (< 5%) in the six probands and one mildly symptomatic sibling but normal (> 50%) in all the parents and the asymptomatic siblings. Ten novel candidate ADAMTS13 mutations were identified in all families, showing either a compound heterozygous or a homozygous status in all probands plus the previous sibling and a heterozygous status in the parents. The mutations were spread all over the gene, involving the metalloprotease domain (I79M, S203P, R268P), the disintegrin domain (29 bp deletion in intron/exon 8), the cystein-rich domain (acceptor splice exon 12, R507Q), the spacer domain (A596V), the 3rd TSP1 repeat (C758R), the 5th TSP1 repeat (C908S) and the 8th TSP1 repeat (R1096stop). This study emphasizes the role of ADAMTS13 mutations in the pathogenesis of congenital TTP and suggests that several structural domains of this metalloprotease are involved in both its biogenesis and its substrate recognition process.     

Analysis of asbestos bodies and nude fibres in the lung parenchyma of operated lung cancers. A retrospective monocentric study of 73 cases

We report on a study concerning a retrospective monocentric series of 73 lung cancers operated on between July 2004 and December 2009. All patients had a mineralogical analysis of a sample of lung tissue combined with an occupational questionnaire. This combination enables us to suggest a declaration of occupational exposure in almost one third of cases. We suggest that a healthy parenchymal fragment is to be obtained by biopsy routinely in cases of lung cancer surgery. The analysis should be carried out if the occupational survey does not demonstrate any evident exposure and if the patient is not known to be presenting a pleuropulmonary disease following asbestos exposure (pleural plaques and asbestosis).     

Antiphospholipid antibodies in HELLP syndrome: clinical and biological study in 68 women

PURPOSE: Pregnancy complicated by the HELLP syndrome and antiphospholipid syndrome have rarely been reported. We report a study on anticardiolipin antibodies in HELLP syndrome. METHODS: Between March 1996 and September 1999, anticardiolipin antibodies were checked in all women with HELLP syndrome hospitalised in a maternity of the North of France. The women with positive anticardiolipin antibodies were seen month later in a internal medicine department. RESULTS: In the period 68 women with HELLP syndrome were checked for anticardiolipin antibodies. Apl were present in 9 patients (Incidence 42.8/1000 HELLP Year). They persisted after the accident only in 3 patients. Antiphospholipid syndrome was diagnosed in 2 patients, prevalence between the HELLP syndrome for the 42 month period was 0.03. CONCLUSIONS: HELLP syndrome may be a manifestation linked to the antiphospholipid syndrome and may revealed it.     

A contactin-receptor-like protein tyrosine phosphatase beta complex mediates adhesive communication between astroglial cells and gonadotrophin-releasing hormone neurones

Although it is well established that gonadotrophin-releasing hormone (GnRH) neurones and astrocytes maintain an intimate contact throughout development and adult life, the cell-surface molecules that may contribute to this adhesiveness remain largely unknown. In the peripheral nervous system, the glycosylphosphatidyl inositol (GPI)-anchored protein contactin is a cell-surface neuronal protein required for axonal-glial adhesiveness. A glial transmembrane protein recognised by neuronal contactin is receptor-like protein tyrosine phosphatase β (RPTPβ), a phosphatase with structural similarities to cell adhesion molecules. In the present study, we show that contactin, and its preferred in cis partner Caspr1, are expressed in GnRH neurones. We also show that the RPTPβ mRNA predominantly expressed in hypothalamic astrocytes encodes an RPTPβ isoform (short RPTPβ) that uses its carbonic anhydrase (CAH) extracellular subdomain to interact with neuronal contactin. Immunoreactive contactin is most abundant in GnRH nerve terminals projecting to both the organum vasculosum of the lamina terminalis and median eminence, implying GnRH axons as an important site of contactin-dependent cell adhesiveness. GT1-7 immortalised GnRH neurones adhere to the CAH domain of RPTPβ, and this adhesiveness is blocked when contactin GPI anchoring is disrupted or contactin binding capacity is immunoneutralised, suggesting that astrocytic RPTPβ interacts with neuronal contactin to mediate glial–GnRH neurone adhesiveness. Because the abundance of short RPTPβ mRNA increases in the female mouse hypothalamus (but not in the cerebral cortex) before puberty, it appears that an increased interaction between GnRH axons and astrocytes mediated by RPTPβ–contactin is a dynamic mechanism of neurone–glia communication during female sexual development.     

Introduction of the intubating Laryngeal Mask Airway in a prehospital emergency medical unit

OBJECTIVES: Assessment of the intubating Laryngeal Mask Airway(trade mark) in a prehospital emergency mobile unit (PEMU). STUDY DESIGN: Observational study. METHODS: All the emergency physicians and nurses of the PEMU were trained with the intubating laryngeal mask (ILMA) handling on manikin and a learning curve was carried out. One year after the initial formation, a reassessment of the operators was performed. Following the initial formation, all the vehicles of the PEMU were equipped with ILMA and during 15 months all cases of ILMA use were recorded. The success rate and the difficulties met were analysed. RESULTS: Initial formation on manikin showed that at least 8 handling of the device were mandatory to achieve a 100% success rate. A significant reduction of tracheal tube insertion delay was observed up to the eight manipulations. One year after the initial formation, a significant loss of performance was observed. Over the clinical study period 20 ILMA were used with adequate ventilation through the mask in all cases and a possible intubation in 80% of the patients. CONCLUSION: The ILMA is a potential useful device in the prehospital setting. Initial formation and maintenance of the skill acquired with this technique are essential.     

Maternal and foetal anaesthesia for ex utero intrapartum treatment (EXIT) procedure

The ex utero intrapartum treatment (EXIT) procedure is a surgical procedure maintaining utero-placental circulation during caesarean section. Anaesthetic implications are described: foetal transplacental anaesthesia to avoid first breathing and to permit surgical procedure on obstructed foetal airway, deep maternal haemodynamically stable anaesthesia to relax uterine smooth muscle during a long caesarean procedure but avoiding post-partum haemorrhage. Volatile anaesthesia with sevoflurane seems to be adequate for these aims. Two cases are described.