Cardiac troponin I as an early prognosis biomarker after trauma: a retrospective cohort study.

BACKGROUND: The significance of cardiac troponin I (cTnI) elevation after trauma is debated. We therefore explored the association between cTnI elevation at admission after trauma and ICU mortality. METHODS: We performed a retrospective analysis from a prospectively constituted database, of patients admitted to ICU after trauma at a single centre, over a 36 month period. According to cTnI plasma concentration at admission, patients were categorised into three groups: normal (<0.05 ng ml-1), intermediate (0.05-0.99 ng ml-1), or high concentration (≥1.0 ng ml-1). Associations of pre-hospital conditions or cTnI elevation and mortality were analysed by multivariate logistic regression. RESULTS: Among the 994 patients, 177 (18%) had cTnI elevation at ICU admission. Of this total, 114 (11%) patients died in the ICU. The cTnI release was an independent predictor of ICU mortality with a concentration-response relationship [odds ratio (OR) 4.90 (2.19-11.16) and 14.83 (4.68-49.90) for intermediate and high concentrations, respectively] and Day 2 mortality [OR 2.23 (1.18-5.80) and 7.49 (2.77-20.12) for intermediate and high concentrations, respectively]. The severity of thoracic trauma [OR 2.25 (1.07-4.55) and 3.23 (2.00-5.27) for Abbreviated Injury Scale scores 1-2 and ≥3, respectively], out-of-hospital maximal heart rate ≥120 beats min-1 [OR 2.22 (1.32-3.69)], and out-of-hospital shock [OR 2.02 (1.20-3.38)] were independently associated with cTnI elevation. CONCLUSIONS: Release of cTnI was an independent predictor of ICU mortality, suggesting that this biomarker can be used in daily practice for early stratification of the risk of ICU death. Thoracic trauma was strongly associated with cTnI elevation.

[Digestive obstruction: an unusual complication of hereditary multiple exostoses]. / Obstruction digestive : une complication exceptionnelle d'une maladie exostosante.

Hereditary multiple exostoses is an autosomal dominant bone disorder characterized by multiple cartilaginous tumors growing outward from metaphyses of long bones. These tumors are usually located in long bones of the limbs. Exostosis also called osteochondroma can cause many complications, the most serious being malignant transformation as chondrosarcoma. We report a rare phenotype of this disease in a young male patient who presents digestive symptoms caused by a voluminous degenerated lumbar exostosis with anterior abdominal development.

[Evaluation of a continuous training program at Bichat hospital for in-hospital cardiac arrest resuscitation]. / Evaluation de la mise en place d'une formation continue du personnel de l'hôpital Bichat à la prise en charge des arrêts cardiocirculatoires intrahospitaliers.

UNLABELLED: Management of in-hospital cardiac arrest is now considered as a hospital quality indicator. Such management actually requires training health care workers (HCWs) for basic life support (BLS). OBJECTIVE: To assess the usefulness and efficacy of a short mandatory BLS training course amongst general ward HCWs in a 1,200 bed teaching hospital. STUDY DESIGN: The in-hospital medical emergency team (MET) established a 45-min BLS training course comprising 10 goals for basic CPR and preparing for the arrival of the MET. Assessment was based on satisfaction questionnaires, cross-sectional evaluation of knowledge and skills of HCWs before and 1 year after the start of the training course. Efficacy of BLS performed on ward was assessed by the MET on scene. RESULTS: One year after, 68 training sessions had been fulfilled and 522 HCWs had been trained (46.27% of total HCWs). HCWs were satisfied with the teaching course. Instant retention of objectives was over 90%. Cross-sectional surveys showed an improvement of BLS knowledge and skills. The knowledge of initial clinical assessment remained low. Knowledge and skills were significantly higher amongst HCWs who had been trained than amongst those who had not. Unfortunately, general ward BLS performance showed no improvement. CONCLUSION: Short mandatory training courses are stimulating and well appreciated amongst HCWs. Although basic knowledge and skills improve dramatically, no improvement of on-scene BLS performance occurs.

[Limits to arterial embolization treatment of severe postpartum hemorrhage]. / Facteurs d'échec de l'embolisation artérielle dans le traitement des hémorragies graves du post-partum.

OBJECTIVE: To assess the limits of arterial embolization in the management of serious postpartum haemorrhage (PPH). STUDY DESIGN: Retrospective study. PATIENTS AND METHODS: We examined the cases of 29 patients admitted to intensive care units of Rouen University Hospital for PPH between January 1994 and August 1999. Demographic, obstetrical and biological data, the required treatment and eventual side effects were collected and analysed using the appropriate parametric and non parametric tests. RESULTS: Arterial embolization was carried out on 15 patients (52%) with a success rate of 73%. Of the 14 other patients, 11 underwent conservative or radical surgery without further complications, three received medical treatment. No maternal death occurred; however, one patient transferred from a local hospital and already presenting haemodynamic instability suffered cardiac arrest before embolization. Arterial embolization was unsuccessful in four cases, two of which were cases of placenta accreta. These patients were older (p < 0.05) and all had a past history of curettage and/or caesarean section for preceding deliveries (p < 0.01). CONCLUSIONS: Emergency arterial embolization is a valuable therapy in case of PPH but can only be carried out in specialised units. Obstetrical antecedents would appear to constitute a major risk factor and transfer increases the morbidity rate.

Identification of an embryonic isoform of myelin basic protein that is expressed widely in the mouse embryo.

We have identified a myelin basic protein (MBP) isoform in mouse embryos that includes an exon upstream of the usual transcription initiation site. This isoform, embryonic-neonatal MBP (E-MBP), is expressed at the protein level in the embryonic nervous system at a time when other MBP isoforms are not detected. In addition to the central and peripheral nervous systems of the embryo and neonate, the thymus, spleen, and testes also express E-MBP at the protein level. The expression of E-MBP in cell types distinct from the nervous system strongly suggests that this MBP isoform has a role apart from the formation of myelin.

Expression of SV-40 T antigen in the small intestinal epithelium of transgenic mice results in proliferative changes in the crypt and reentry of villus-associated enterocytes into the cell cycle but has no apparent effect on cellular differentiation programs and does not cause neoplastic transformation.

The mouse intestinal epithelium represents a unique mammalian system for examining the relationship between cell division, commitment, and differentiation. Proliferation and differentiation are rapid, perpetual, and spatially well-organized processes that occur along the crypt-to-villus axis and involve clearly defined cell lineages derived from a common multipotent stem cell located near the base of each crypt. Nucleotides -1178 to +28 of the rat intestinal fatty acid binding protein gene were used to establish three pedigrees of transgenic mice that expressed SV-40 large T antigen (TAg) in epithelial cells situated in the uppermost portion of small intestinal crypts and in already committed, differentiating enterocytes as they exited these crypts and migrated up the villus. T antigen production was associated with increases in crypt cell proliferation but had no apparent effect on commitment to differentiate along enterocytic, enteroendocrine, or Paneth cell lineages. Single- and multilabel-immunocytochemical studies plus RNA blot hybridization analyses suggested that the differentiation programs of these lineages were similar in transgenic mice and their normal littermates. This included enterocytes which, based on the pattern of [3H]thymidine and 5-bromo-2'-deoxyuridine labeling and proliferating nuclear antigen expression, had reentered the cell cycle during their migration up the villus. The state of cellular differentiation and/or TAg production appeared to affect the nature of the cell cycle; analysis of the ratio of S-phase to M-phase cells (collected by metaphase arrest with vincristine) and of the intensities of labeling of nuclei by [3H]thymidine indicated that the duration of S phase was longer in differentiating, villus-associated enterocytes than in the less well-differentiated crypt epithelial cell population and that there may be a block at the G2/M boundary. Sustained increases in crypt and villus epithelial cell proliferation over a 9-mo period were not associated with the development of gut neoplasms--suggesting that tumorigenesis in the intestine may require that the initiated cell have many of the properties of the gut stem cell including functional anchorage.

Pathogenesis of corneal epithelial defects: role of plasminogen activator.

Previous studies have suggested that the plasminogen activator (PA)/plasmin system has important roles in the pathogenesis of epithelial defects and stromal ulceration. The current studies were performed to localize PA species and identify them as tissue-type PA (tPA) or urokinase-like PA (uPA) as the two have distinct regulatory properties potentially related to the mechanisms of defect formation and ulceration. To determine the locations and types of PA species, antibodies to tPA or to uPA or the drug amiloride (a drug that inhibits uPA but not tPA) were incorporated into fibrin/fibronectin (Fn) clots overlying frozen sections to block regional fibrinolysis. Normal rabbit eyes showed tPA activity in association with corneal epithelium, corneal endothelium, and ciliary body/iris. After epithelial scrape or alkali burn, corneal tPA activity was detected initially in the defect zone colinear with fibrin/Fn and was symmetrical to resurfacing epithelium. The observation that initial fibrinolysis occurs in the defect zone, known to contain fibrin/Fn, suggests that tPA from blood (limbal vascular endothelium) and/or from corneal epithelium has become bound to (and activated on) the fibrin/Fn. PA activity was also associated with the leading edges of migrating epithelium post-scrape and post-burn and was not inhibited by antibodies to either tPA or uPA but was inhibited by amiloride. After complete closure of the primary defect post-scrape, only tPA appeared to be associated with the epithelium in that all PA activity was inhibited by antibodies to tPA. The observation that leading edge activity post-burn, in correlation with the formation of secondary defects, continues to be inhibitable by amiloride but not by antibodies to tPA suggests that uPA remains abnormally on the leading edge, and that sustained uPA activity in that location results in inappropriate degradation of subepithelial fibrin/Fn to result in a defect. Successful regulation of uPA activity at the leading edge of corneal epithelium post-burn would be expected to be useful therapeutically in the healing of epithelial defects and the prevention of stromal ulceration.

Formation of germ-line chimeras from embryonic stem cells maintained with recombinant leukemia inhibitory factor.

Murine embryonic stem (ES) cells can be maintained as stem cells in vitro only in the presence of feeder cells or a soluble factor produced by a number of cell lines. We have previously demonstrated that leukemia inhibitory factor (LIF) is the molecule which prevents ES cell differentiation in culture. In this report we demonstrate that recombinant LIF can substitute for feeder cells in maintaining the full developmental potential of ES cells. The totipotent D3 ES cell line, previously isolated and maintained on growth-arrested primary embryo fibroblasts, was transferred to media supplemented with 1000 U/ml (10 ng/ml) recombinant LIF. In the presence of LIF the ES cells were maintained for over 2 months as undifferentiated cells in the absence of any feeder cells. When injected into blastocysts the ES cells which had been maintained in LIF-supplemented media efficiently formed germ-line chimeras.

Isolation of embryonic stem (ES) cells in media supplemented with recombinant leukemia inhibitory factor (LIF).

The isolation of pluripotent murine embryonic stem (ES) cells has previously been achieved by coculturing the ES cells with fibroblast feeder cells. In this report we demonstrate that ES cell lines can be isolated from murine 129/Sv He blastocysts in the absence of feeder cells in culture medium supplemented with recombinant leukemia inhibitory factor (LIF). Three of the ES cell lines (MBL-1, MBL-2, and MBL-3) were isolated by directly explanting blastocysts, whilst two ES cell lines (MBL-4 and MBL-5) were isolated from blastocysts pretreated by immunosurgery. Three of the ES cell lines contained the Y chromosome (MBL-1, MBL-2, and MBL-5) with a high proportion of the cells displaying a normal diploid karyotype with a modal chromosome number of 40. All of the ES cell lines tested expressed the stem cell markers ECMA-7 and alkaline phosphatase, which were lost on removal of LIF when the ES cells differentiated into a variety of cell types. The full developmental potential of the ES cells was determined by injecting cells from two of the independently derived ES cell lines, MBL-1 and MBL-5, into C57BL/6J blastocysts. A high proportion of the pups born were chimeric as judged by coat pigmentation. Subsequent breeding established that the ES cells had contributed to the germ line. These results demonstrate that feeder cells are not essential for the isolation of pluripotent ES cell lines.

LIF: a molecule with divergent actions on myeloid leukaemic cells and embryonic stem cells.

We have previously characterized, purified and cloned a novel murine and human regulator [leukaemia inhibitory factor, LIF] which induces the differentiation of certain murine and human myeloid leukaemic cells. Recently we have shown that there are specific LIF receptors on murine embryonic stem [ES] and embryonal carcinoma [EC] cells and that purified recombinant LIF can substitute for feeder cells and crude sources of differentiation inhibiting activity [DIA] [such as BRL-cell-conditioned medium] in the maintenance of ES cells in a pluripotential state in vitro. Furthermore, ES cells maintained in culture in recombinant LIF for a prolonged period can give rise to germline chimaeric mice. Thus, based on a number of biochemical and biological similarities, it is likely that LIF and DIA are the same molecule. The identification of LIF as a molecule, necessary and sufficient for the maintenance of ES cells in culture, should have a profound impact on the use of these cells for genetic manipulations.

Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells.

Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.

Vaccination with syngeneic monoclonal anti-idiotype protects against a tumour challenge.

Rat X rat hybridomas secreting monoclonal anti-idiotypic antibodies have been prepared from Hooded rats immunized with two tumour-reactive, syngeneic monoclonal antibodies 11/160 and M10/76 (specific, respectively, for the Hooded rat sarcomata HSN and MC24). The hybridomas were selected on the basis that the secreted antibodies competed with antigen for binding to the immunizing idiotype. One monoclonal anti-idiotype (HIM/1/230, gamma 2a isotype) that recognizes an antigen-binding site idiotope of antibody 11/160 has been found to substitute for antigen. Hooded rats vaccinated by three challenges with HIM/1/230 produce serum Ab3 that is indistinguishable in antigen specificity from the 11/160 Ab1, and show reduced tumour take following an i.v. challenge with 10(6) HSN cells. The response to vaccination with anti-idiotype was both qualitatively and quantitatively dependent on the mode of immunization. High titre 11/160-like Ab3 was generated only when the vaccine contained Freund's adjuvant, whereas resistance to tumour challenge was found only in animals vaccinated with anti-idiotype in the absence of adjuvant.

The establishment of a breeding nucleus of category 4 Dutch rabbits.

A method is described for establishing a breeding nucleus of Category 4 Dutch rabbits. The problems of hand-rearing, causes of mortality and the failure of the does to lactate normally are discussed.