[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.

Alveolar neutrophil oxidative burst and beta2 integrin expression in experimental acute pulmonary inflammation are not modified by inhaled nitric oxide.

It was recently proposed that nitric oxide (NO) inhalation interferes with polymorphonuclear neutrophil (PMN) activation status during acute pulmonary inflammation, although variable results have been observed considering timing of NO administration, species, and model differences. After intratracheal administration of lipopolysaccharide (LPS) in rats, we characterized pulmonary inflammatory reaction (lung wet, dry, and wet to dry weights) and, using flow cytometry, the activation status (H2O2 production and beta2 integrin CD11b/CD18 expression) of PMN obtained from blood and from bronchoalveolar lavage (BAL). Eight hours after LPS injection, rats received for an additional 10 h, at a same Fio2 (85%), either 15 parts per million NO or the same gas flow of nitrogen. We found that 18 h after LPS, lung wet, dry, and wet-to-dry weights, H2O2 production, and CD11b/CD18 expression were increased. PMN obtained from BAL were highly activated as evidenced by an already maximal expression of the beta2 integrin CD11b/CD18, whereas the high H2O2 production at basal state could be further enhanced after ex vivo stimulation. Blood PMN were not different from control cells at basal state; however, their increased capacity to be stimulated ex vivo suggested an in vivo priming effect of intratracheal LPS. In conclusion, inhaled NO, given with a high FiO2, in the presence of this established endotoxinic lung injury did not reverse the markers of PMN activation studied nor lung edema formation in this rat model.

[Infections related to external ventricular drainage]. / Infections sur matériel de dérivation ventriculaire externe.

Infection is the main complication of external ventricular drainage (EVD). This retrospective study assessed the relationships between EVD duration, antibiotics and cerebrospinal fluid (CSF) infection. From January 1990 to December 1991, 53 neurosurgical patients, aged 7-76 years, a simplified acute physiological score (SAPS) of 1-20 and having a total of 64 EVD, were included in this study. CSF withdrawn from the drain was collected daily for bacteriological, biochemical and cytological analysis, until the EVD removal. CSF colonization was defined by a positive direct examination or a positive culture of CSF, in the absence of biochemical and cytological abnormalities. CSF drain infection was defined by a low glucose concentration or leucocytosis without blood contamination. However the results of bacteriological analysis were modified by the antibiotics. The group of non infected patients and the group of those with an infected or a colonized drain were comparable with regard to underlying neurosurgical diseases, age, SAPS, Glasgow coma scale and delay between hospital admission and day of drain insertion and antibiotic administration. The EVD duration was significantly longer in infected EVD and colonized EVD. Staphylococci were the most frequently recognized bacteria and coagulase-negative staphylococci predominated in CSF of colonized EVD. In five patients, antibiotics were unable to cure a meningitis. Their leucocyte count was increased. The glucose concentration was low, but the culture, remained negative. It is concluded that duration and rate of EVD influence more the incidence of infections than the systemic administration of antibiotics.

Comparison of allele O sequences of the human and non-human primate ABO system.

Like humans, non-human primates express the antigens A and B of the ABO histoblood group system. In chimpanzees, only A and O types are found, while the types A, B, AB, and O are found in macaques. The sequences of exons 6 and 7 of two chimpanzee O alleles (Odel and O(x), two macaque species O alleles (rhesus monkey and crab-eating macaque), and sequences of exon 7 of two major chimpanzee A alleles (A1ch and A2ch) were established. The sequences of cDNAs corresponding to the chimpanzee and rhesus monkey O alleles were characterized from exon 1 to 7 and from exon 4 to 7, respectively. A comparison of our results with ABO gene sequences already published by others demonstrates that human and non-human primate O alleles are species-specific and result from independent silencing mutations. These observations reinforce the hypothesis that the maintenance of the ABO gene polymorphism in primates reflects convergent evolution more than transpecies inheritance of ancestor alleles.

Alveolar neutrophil functions and cytokine levels in patients with the adult respiratory distress syndrome during nitric oxide inhalation.

It was recently demonstrated that nitric oxide (NO) inhalation improves arterial oxygenation in patients with the adult respiratory distress syndrome (ARDS). However, the potential adverse reaction of NO on inflammatory cells and mediators in the lung has not yet been investigated. In this study, we evaluated the impact of NO inhalation on lung polymorphonuclear neutrophil (PMN) activation and proinflammatory cytokine release, both of which are involved in the pathophysiology of ARDS. Two groups of patients with ARDS of similar etiologies were compared; one received NO (n=9) and the other did not (n=5). After 4 d of NO inhalation (18 ppm), PMN form bronchoalveolar lavage (BAL) showed a reduction in both spontaneous H2O2 production (p<0.05) and beta 2 integrin CD11b/CD18 expression (p<0.05). Moreover, the high levels of IL8 and IL-6 decreased in BAL fluid supernatants after NO inhalation (p<0.05). In the NO-untreated group of patients with ARDS, neither PMN activation nor levels of IL-8 and IL-6 in BAL fluid changed significantly on Day 4. These results suggest that NO inhalation might reduce lung inflammation in ARDS, as reflected by PMN activation status and IL-8/IL-6 release.

Impact of inhaled nitric oxide on platelet aggregation and fibrinolysis in rats with endotoxic lung injury. Role of cyclic guanosine 5'-monophosphate.

As inhaled nitric oxide (iNO) may differently increase bleeding time (BT) and inhibit platelet aggregation in normal and lung-injured patients or experimental models, we studied the effects of iNO on hemostasis in presence and absence of an endotoxic lung injury in the rat. Eight hours after intratracheal administration of endotoxin (lipopolysaccharide [LPS]) or its solvent (phosphate-buffered solution [PBS]), four groups of rats were randomized according to the presence or absence of 15 ppm iNO added for an additional 10 h. We measured BT, ex vivo platelet aggregation, plasma fibrinogen, euglobulin clot lysis time (ECLT), and platelet and aortic cyclic guanosine 5'-monophosphate (cGMP) contents. Acute lung inflammation did not influence BT, but increased platelet aggregability, fibrinogen levels, and platelet and aortic cGMP. In control and endotoxic rats, iNO increased BT, reduced platelet aggregability, and increased platelet cGMP. iNO increased aortic cGMP only in healthy rats. ECLT was increased by LPS and unchanged with iNO. These results suggest that the extrapulmonary "systemic" effects induced by iNO on hemostasis were not strictly similar in healthy and LPS rats, inflammation inducing proper changes in coagulation parameters. However, iNO attenuated the procoagulant activity induced by acute lung inflammation, suggesting a potentially beneficial effect of this therapy.

Molecular polymorphism of O alleles in five populations of different ethnic origins.

Sequences of exons 6 and 7 of the O allele of the ABO gene were studied in 317 individuals of the O phenotype from five different ethnic groups (Basques, Berbers, Akans from the Ivory Coast, and Amerindians: Cayapas from Ecuador and Aymaras from Bolivia). Twenty-one O alleles were characterized, among which 9 differed from all O alleles reported to date. The nine alleles differed from either the O01 allele (four out of nine) or O02 allele (five out of nine) by one to three point mutations. The number of different O alleles in population samples varied greatly: the highest number (13) was observed in Akans, and the lowest (5) in Amerindians. Some rare alleles previously reported by others at low frequencies were found with high frequencies in the Akans. The results also revealed a decreasing frequency of Ov7 alleles from south to north (Akans, Berbers, Basques). Berbers and Basques share two rare alleles, Ov6 and O03, which were not encountered in the other populations studied here.

Cytokines and soluble cytokine receptors in pleural effusions from septic and nonseptic patients.

The balance between proinflammatory cytokines and their inhibitors has rarely been investigated in pleural effusions of nonmalignant or noninfectious origin. To evaluate the impact of a lung and/or intrathoracic infection in such a circumstance, we compared the levels of proinflammatory cytokines (interleukin-8 [IL-8]); tumor necrosis factor-alpha (TNF-alpha); the cytokine antagonists and inhibitors (IL-1 receptor antagonist [IL-1ra]) and soluble TNF receptors Types I and II (sTNFRI, sTNFRII); and antiinflammatory cytokines (transforming growth factor-beta [TGF-beta]) in pleural effusion and plasma from septic (n = 15) and nonseptic (n = 9) patients. In addition, we analyzed the levels of IL-6 and its soluble receptor (sIL-6R). Bronchoalveolar lavage fluids (BALFs) were also studied in a few septic patients. High and nonsignificantly different levels of cytokines and inhibitors were detected in both groups of patients. The levels of IL-6 and sTNFRI and sTNFRII in pleural effusion were higher than in plasma, whereas the levels of IL-1ra and sIL-6R were higher in plasma. The levels of sIL-6R influenced the bioactivity of IL-6. There was no correlation between the levels of cytokines in plasma and in pleural effusion. In contrast, a significant correlation was observed for the soluble receptors sIL-6R (r = 0.67, p < 0.001), sTNFRI (r = 0.76, p < 0.001) and sTNFRII (r = 0.66, p = 0.001). Furthermore, a high correlation was found between the levels of both forms of sTNFRs in plasma (r = 0.95, p < 0.001) and in pleural effusion (r = 0.79, p < 0.001). In addition, a correlation was observed between the levels of TGF-beta in pleural effusion and in BALF. The highest levels of some markers in plasma and of others in pleura argue in favor of both a systemic and a compartmentalized response, independently of the presence of infection. Because cytokines can be trapped by the surrounding cells in their environment, measurable levels of cytokines in biologic fluids represent the "tip of the iceberg," which is not the case for soluble receptors. The correlations of these latter markers between plasma and pleura strongly suggest that exchanges between both compartments can occur in both directions.

Inhaled nitric oxide, almitrine infusion, or their coadministration as a treatment of severe hypoxemic focal lung lesions.

BACKGROUND: The partition of pulmonary blood flow between normal and shunting zones is an important determinant of oxygen tension in arterial blood (PaO2). The authors hypothesized that the combination of inhaled nitric oxide (iNO) and almitrine infusion might have additional effects related to their pharmacologic properties to improve PaO2. Such a combination was tested in patients with hypoxia caused by focal lung lesions, distinct from the acute respiratory distress syndrome. METHODS: Fifteen patients with hypoxic focal lung lesions despite optimal therapy were included and successively treated with (1) 5 ppm iNO, (2) low-dose almitrine infusion (5.5 +/- 1.7 microg x kg(-1) min(-1)) during iNO, and (3) almitrine infusion alone (with NO turned off). Then iNO was reintroduced and we studied the effect of the coadministration in reducing the fractional concentration of oxygen in inspired gas (FI(O2)) and positive end-expiratory pressure (PEEP) levels. Changes in blood gases and pulmonary and systemic hemodynamics were measured. RESULTS: Systemic hemodynamic variables remained stable in all protocol conditions. Use of iNO improved arterial oxygenation and decreased intrapulmonary shunt. Almitrine similarly improved PaO2 but increased pulmonary artery pressure and right atrial pressure. Coadministration of iNO and almitrine improved PaO2 compared with each drug alone and with control. All patients responded (that is, they had at least a +30% increase in PaO2) to this coadministration. When the drug combination was continued, FI(O2) and PEEP could be reduced over 8 h. The hospital mortality rate was 33% and unrelated to hypoxia. CONCLUSIONS: In hypoxemic focal lung lesions, iNO or low-dose almitrine markedly improved PaO2 to a similar extent. Furthermore, the coadministration amplified the PaO2 increase at a level that allowed reductions in FI(O2) and PEEP levels.

Genetic study of gold-salt-induced immune disorders in the rat.

BACKGROUND: Rheumatoid arthritis patients treated with gold salts occasionally develop a glomerulonephritis and an increase in serum IgE concentration. Brown-Norway (BN) rats injected with aurothiopropanolsulphonate (ATPS) exhibit an increase in serum IgE concentration, produce antilaminin antibodies (Abs) and develop glomerular linear immunoglobulin (Ig) deposits, occasionally a membranous glomerulopathy and vascular granular Ig deposits. Lewis (LEW) rats are resistant. METHODS: The genetic requirements governing the appearance of these manifestations were studied in congenic rats, and in F1 hybrids injected with ATPS. RESULTS: Non-MHC-linked genes from the BN strain were absolutely required for all the traits to be observed. The RT1n (BN) or RT1(1) (LEW) haplotypes at the MHC were permissive for all the manifestations to appear and two RT1(1) alleles were associated with the highest response. However, granular Ig deposits were only observed in RT1n rats. The high serum IgE concentration and the antilaminin Ab level were associated with the presence of glomerular Ig deposits but were not associated with the presence of vascular Ig deposits. CONCLUSIONS: This study shows that susceptibility to ATPS was mainly dependent upon non-MHC-linked BN genes and that the involvement of MHC-linked genes differed depending upon the character considered. There is an epistatic effect between the various genes.

Target lysis by human LAK cells is critically dependent upon target binding properties, but LFA-1, LFA-3 and ICAM-1 are not the major adhesion ligands on targets.

The cytotoxicity mediated by the CD2+ CD3- lymphocyte subset, either NK or LAK, is puzzling since no specific antigen recognition structures, equivalent to the CD3-associated heterodimer T-cell receptor, have been recognized on these cells so far. The possibility exists that the CD3- cytotoxic effectors recognize their targets through non-specific adhesion mechanisms. The goal of this study was: (a) to examine the correlation between binding properties and susceptibility to lysis of 6 informative target cell lines; (b) to evaluate the role, as ligands on these targets, of adhesion molecules such as LFA-1, LFA-3 and ICAM-1. The effectors used in this study were IL-2-activated LGL, predominantly CD3-, or highly purified CD3- lymphocytes from normal human donors. The 6 target lines studied included 2 pairs of EBV-transformed B-cell lines (721 LCL vs. 721.134, and MM vs. MM-10F2) in which the parental lines were resistant to lysis while HLA variants were susceptible. A third pair was the Daudi Burkitt cell line, susceptible to LAK lysis, and an HLA-positive transfected Daudi line which was more resistant to lysis. The binding properties of these targets to LAK effectors (conjugate formation) were evaluated using a sensitive double fluorescence flow cytometry method. In each pair examined, the susceptible targets formed more conjugates and were surrounded by more cytotoxic LAK effectors than their resistant counterparts, indicating that the conjugation properties of targets are closely correlated with their susceptibility to LAK lysis. The expression of adhesion molecules on the informative targets was examined by indirect immunofluorescence and their role was evaluated by inhibition of lysis after pre-coating the targets with the relevant antibodies. The differences in the expression of the classical cell-cell adhesion molecules LFA-1, LFA-3 and ICAM-1 on the target surfaces were only marginal, insufficient to explain the striking differences in susceptibility to lysis and in binding properties. Coating the target cells with antibodies directed against these adhesion determinants had no effects on the lysis of susceptible target cells. The same antibodies reacting with the LAK effectors did inhibit lysis. Taken together, these results suggest that, on the targets, presently undefined membrane adhesion structures may have a major role in conjugate formation between target and CD3- effectors and determine the susceptibility of the targets to lysis.

Rat chromosome 9 bears a major susceptibility locus for IgE response.

Injection of Brown Norway (BN) rats with gold salts provides a model to analyze the genetic control of the IgE response. A cohort of F2 progeny of susceptible BN and resistant LEW strains has been studied to carry out a genome-wide search for loci controlling the IgE response. Genome scanning identified two previously described loci, Atps1 and Atps2, and a new locus, Atps3. Atps1 linked to the MHC and Atps2 linked to the cytokine gene cluster that included the IL-4 region have been previously associated with serum IgE concentrations and with other Th2-dependent immune manifestations triggered by gold salts. The new interval, Atps3, identified on chromosome 9 (Lod score = 16), appears to play a major role in the control of the IgE response since it accounts for 31% of the genetic variance. Moreover, Atps3 is linked to anti-laminin antibody response and to glomerular immunoglobulin deposits. The identification and functional characterization of genes involved in these regions, particularly in Atps3, may shed light on the pathogenesis of atopic diseases in man.

Serum IgE concentration and other immune manifestations of treatment with gold salts are linked to the MHC and IL4 regions in the rat.

A subset of patients with rheumatoid arthritis occasionally develops skin reactions and glomerulonephritis and exhibits an increase in serum IgE concentration when treated with gold salts. Brown-Norway (BN) rats injected with aurothiopropanolsulfonate (ATPS) also manifest an autoimmune glomerulonephritis and increased serum IgE concentration, whereas Lewis (LEW) rats are resistant to complications. Here, we show linkage between responses to ATPS in a (BN x LEW) F2 cohort and the major histocompatibility complex (RT1) on rat chromosome 20 and between markers in the region of IL4 and other candidate genes on rat chromosome 10. Recently, human serum IgE concentration has been reported to be linked to the IL-4 region. Taken together, these findings raise the possibility that homologous genes could be implicated in ATPS manifestations in the rat and in the regulation of IgE levels in the human.