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P Moine

Publications and source records attributed to P Moine.

At least 19 recordsLinked to original sources
PubMed2006

[ICU performance: results of a French study involving 80,000 ICU stays].

OBJECTIVE: The Standard Mortality Ratio (SMR), comparing the observed in-hospital mortality to the predicted, may measure the intensive care units (ICU) performance. STUDY DESIGN: Multicentric retrospective national study. METHODS: A probability model using a severity score such SAPS II calculated the predicted mortality rate. A national French study has been undertaken to compare the SMR of ICUs and looked for explanation. RESULTS: One hundred six units, 34 were medical (32%), 18 surgical (17%) and 57 medical/surgical (51%) participated to the study. Forty-six ICUs (43%) were located in teaching hospitals. The SMR of the 87,099 stays was 0.84 (0.82-0.85). The SMR of ICUs varied from 0.41 to 1.55. Ten units had a SMR>0.85, which suggested a low performance. They had more stays for cardiovascular failures, as compared with others. The best units (SMR<0.82) had more stays for drug overdose. The SMR increased with the number of organ failures, from 0.47 with zero failure to 1.11 with 4 or more organ failures. The stays with cardiovascular failure, either unique or associated, had a higher SMR. The 7935 stays with a drug overdose had a SMR of 0.12 (0.10-0.14), which suggested a bad calibration of the model in theses cases. CONCLUSION: The case mix must be taken in account when comparing the ICUs performance by the mean of SMR, particularly when the units admitted a lot of drug overdoses.

Cardiovascular Diseases↗
PubMed2005

[Differential modulation of TLR2 and TLR4-induced TNF production by murin haemorrhagic shock].

OBJECTIVE: To investigate the influence of haemorrhagic shock in mice on ex vivo TNF production by whole blood cells (WBC) stimulated through Toll-like receptors (TLR) 4 and 2. STUDY DESIGN AND ANIMALS: Experimental study using BALB/c male mice. METHODS: Haemorrhage (0,026+/-0,003 ml/g) by transparietal cardiac puncture under general anaesthesia. Measurement of left intraventricular pressure through a direct subcostal cardiac puncture. Possible restitution of shed blood volume (SBV) in retroorbital venous plexus, 60 minutes following haemorrhage. Lethal exsanguination 120 minutes following general anaesthesia (Control group), cardiac puncture (Sham group), blood sample (Haemorrhage group), or 60 minutes following SBV retransfusion (SBV group). Cultures (24 hours) of whole blood from the exsanguination, alone or with Escherichia coli endotoxin (LPS, TLR 4) or with heat-killed Staphylococcus aureus Cowan (SAC, TLR 2). Assessment of TNF levels in the cultures supernatant (Elisa). RESULTS: Hemorrhage (approximately 30% of calculated blood volume) resulted in arterial hypotension (-50%) which was reversed by SBV retransfusion. TNF production by LPS-stimulated WBC was reduced by haemorrhage (approximately -50%) with or without SBV retransfusion. TNF production by SAC-stimulated WBC remained unchanged. CONCLUSION: The reduction of proinflammatory cytokines production by WBC stimulated with pathogen-associated molecular patterns is not a generalized phenomenon following murin haemorrhagic shock. It depends on the used stimulus and studied signalling pathways.

Animals↗
PubMed2005

Activity of gemifloxacin against quinolone-resistant Streptococcus pneumoniae strains in vitro and in a mouse pneumonia model.

Gemifloxacin is a novel fluoronaphthyridone quinolone with enhanced in vitro activity against Streptococcus pneumoniae. We investigated the activities of gemifloxacin and trovafloxacin, their abilities to select for resistance in vitro and in vivo, and their efficacies in a mouse model of acute pneumonia. Immunocompetent Swiss mice were infected with 10(5) CFU of a virulent, encapsulated S. pneumoniae strain, P-4241, or its isogenic parC, gyrA, parC gyrA, and efflux mutant derivatives (serotype 3); and leukopenic mice were infected with 10(7) CFU of two poorly virulent clinical strains (serotype 11A) carrying either a parE mutation or a parC, gyrA, and parE triple mutation. The drugs were administered six times every 12 h, starting at either 3 or 18 h postinfection. In vitro, gemifloxacin was the most potent agent against strains with and without acquired resistance to fluoroquinolones. While control mice died within 6 days, gemifloxacin at doses of 25 and 50 mg/kg of body weight was highly effective (survival rates, 90 to 100%) against the wild-type strain and against mutants harboring a single mutation, corresponding to area under the time-versus-serum concentration curve at 24 h (AUC(24))/MIC ratios of 56.5 to 113, and provided a 40% survival rate against a mutant with a double mutation (parC and gyrA). A total AUC(24)/MIC ratio of 28.5 was associated with poor efficacy and the emergence of resistant mutants. Trovafloxacin was as effective as gemifloxacin against mutants with single mutations but did not provide any protection against the mutant with double mutations, despite treatment with a high dose of 200 mg/kg. Gemifloxacin preferentially selected for parC mutants both in vitro and in vivo.

Animals↗
PubMed2004

[Completeness of ICU activity reports sent to French healthcare authorities].

INTRODUCTION: Hospital units report on their inpatient care activity by writing yearly activity reports, which are used by their Medical Information Department (MID) to develop standardized summaries for communication to healthcare authorities. The data are categorized by uniform patient groups and used to describe inpatient care activity and to guide resource allocation. The objective of this study was to evaluate the completeness of activity reports from intensive care units (ICUs) in France. METHODS: Activity reports sent in 1998 and 1999 by French ICUs participating in the study were collected using dedicated abstracting software supplied to the relevant MIDs. Completeness of data in the activity reports was evaluated, with special attention to the SAPSII score, Omega rating of ICU procedures according to the Classification of Medical Procedures, and primary and secondary diagnoses. RESULTS: The 106 ICUs that volunteered for the study reported data on 107,652-hospital stays. Mean age and SAPSII were 55 +/- 21 years and 35 +/- 21 years, respectively. Mean ICU and hospital lengths of stay were 6.2 +/- 12.4 and 16.1 +/- 21.6 days, respectively. Mean ICU and hospital mortality rates were 15% and 19%. The SAPSII and Omega procedures were reported for 81% and 80% of stays, respectively. The SAPSII and Omega procedures were calculated or coded in 94% (100/106) and 96% (102/106) of ICUs, respectively. Mean number of Omega procedures was 4.3+/-3.9. However, only 5% (5/106) of ICUs entered the SAPSII for every stay, and 21% (22/106) of ICUs failed to enter the SAPSII for over 20% of stays. Similarly, 53% (56/106) of ICUs rated no more than five Omega procedures on average per stay. The primary diagnosis was reported for all stays, and the mean number of secondary diagnoses was 3.5 +/- 3.8. In 80% (86/106) of ICUs, no more than five secondary diagnoses were coded on average per stay. CONCLUSION: The analysis of this national database shows that data communicated to the MIDs and therefore to the healthcare authorities, are incomplete regarding SAPSII, ICU procedures, treatment intensity, and diagnoses. This may lead to the underestimation of ICU activity and resource needs, particularly if the SAPSII and selected procedures identified as markers for high-intensity critical care are used in the future.

Age Factors↗
PubMed2004

Activities of garenoxacin against quinolone-resistant Streptococcus pneumoniae strains in vitro and in a mouse pneumonia model.

Garenoxacin is a novel des-F(6) quinolone with enhanced in vitro activities against both gram-positive and gram-negative bacteria. We compared the activity of garenoxacin with that of trovafloxacin (TVA) against Streptococcus pneumoniae, together with their efficacies and their capacities to select for resistant mutants, in a mouse model of acute pneumonia. In vitro, garenoxacin was more potent than TVA against wild-type S. pneumoniae and against a mutant with a single mutation (parC), a mutant with double mutations (gyrA and parC), and a mutant with triple mutations (gyrA, parC, and parE). Swiss mice were infected with 10(5) CFU of virulent, encapsulated S. pneumoniae strain P-4241 or its derived isogenic parC, gyrA, gyrA parC, and efflux mutants and 10(7) CFU of poorly virulent clinical strains carrying a parE mutation or gyrA, parC, and parE mutations. The drugs were administered six times, every 12 h, beginning at either 3 or 18 h postinfection. The pulmonary pharmacokinetic parameters in mice infected with strain P-4241 and treated with garenoxacin or TVA (25 mg/kg of body weight) were as follows: maximum concentration of drug in serum (C(max); 17.3 and 21.2 micro g/ml, respectively), C(max)/MIC ratio (288 and 170, respectively), area under the concentration-time curve (AUC; 48.5 and 250 microg. h/ml, respectively), and AUC/MIC ratio (808 and 2000, respectively). Garenoxacin at 25 and 50 mg/kg was highly effective (survival rates, 85 to 100%) against the wild-type strain and mutants harboring a single mutation. TVA was as effective as garenoxacin against these strains. TVA at 200 mg/kg and garenoxacin at 50 mg/kg were ineffective against the mutant with the parC and gyrA double mutations and the mutant with the gyrA, parC, and parE triple mutations. The efficacy of garenoxacin was reduced only when strains bore several mutations for quinolone resistance.

Animals↗
PubMed2001

[Off-label prescriptions in an adult surgical intensive care unit].

OBJECTIVE: The aim of the study was to document off label prescribing in an adult surgical intensive care unit setting and to determine explanatory factors. METHOD: Medical prescriptions of 20 adult patients consecutively admitted in surgical intensive care unit were recorded, from the time of admission to the second day of hospitalisation. Concordance of each prescription to the different sections listed on the approved labeling was checked on the Vidal 1999 dictionary. French guidelines promoted by the two major intensive care societies were looked for to explain the most frequent reason of unapproved use of the 10 main therapeutic classes concerned by off label prescription. RESULTS: In this study, 465 prescriptions were analysed, representing 80 drugs and 35 therapeutic classes. Prescriptions were considered off label in 25.6%. Antibiotics, stress ulcer prophylactic drugs, vitamins, antiepileptic drugs were the main therapeutic classes used off label. The main cause of off label prescription was unapproved indication (66%), dosing schedule (27%) and method of administration (17%). For 5 therapeutic classes, representing 45% of off label prescriptions, a guideline supporting these prescriptions was available or was published in the year following the study. CONCLUSION: Off label prescription is frequent in the setting of adult surgical intensive care unit. Seldom medical situations and the gap between official labeling and medical knowledge are explanatory factors of these off label prescriptions.

Adolescent↗
PubMed2001

Accuracy of a composite score using daily SAPS II and LOD scores for predicting hospital mortality in ICU patients hospitalized for more than 72 h.

UNLABELLED: In most databases used to build general severity scores the median duration of intensive care unit (ICU) stay is less than 3 days. Consequently, these scores are not the most appropriate tools for measuring prognosis in studies dealing with ICU patients hospitalized for more than 72 h. PURPOSE: To develop a new prognostic model based on a general severity score (SAPS II), an organ dysfunction score (LOD) and evolution of both scores during the first 3 days of ICU stay. DESIGN: Prospective multicenter study. SETTING: Twenty-eight intensive care units (ICUs) in France. PATIENTS: A training data-set was created with four ICUs during an 18-month period (893 patients). Seventy percent of the patients were medical (628) aged 66 years. The median SAPS II was 38. The ICU and hospital mortality rates were 22.7% and 30%, respectively. Forty-seven percent (420 patients) were transferred from hospital wards. In this population, the calibration (Hosmer-Lemeshow chi-square: 37.4, P = 0.001) and the discrimination [area under the ROC curves: 0.744 (95 % CI: 0.714-0.773)] of the original SAPS II were relatively poor. A validation data set was created with a random panel of 24 French ICUs during March 1999 (312 patients). MEASUREMENTS AND MAIN RESULTS: The LOD and SAPS II scores were calculated during the first (SAPS1, LOD1), second (SAPS2, LOD2), and third (SAPS3, LOD3) calendar days. The LOD and SAPS scores alterations were assigned the value "1" when scores increased with time and "0" otherwise. A multivariable logistic regression model was used to select variables measured during the first three calendar days, and independently associated with death. Selected variables were: SAPS II at admission [OR: 1.04 (95 % CI: 1.027-1.053) per point], LOD [OR: 1.16 (95 % CI: 1.085-1.253) per point], transfer from ward [OR: 1.74 (95 % CI: 1.25-2.42)], as well as SAPS3-SAPS2 alterations [OR: 1.516 (95 % CI: 1.04-2.22)], and LOD3-LOD2 alterations [OR: 2.00 (95 % CI: 1.29-3.11)]. The final model has good calibration and discrimination properties in the training data set [area under the ROC curve: 0.794 (95 % CI: 0.766-0.820), Hosmer-Lemeshow C statistic: 5.56, P = 0.7]. In the validation data set, the model maintained good accuracy [area under the ROC curve: 0.826 (95 % CI: 0.780-0.867), Hosmer-Lemeshow C statistic: 7.14, P = 0.5]. CONCLUSIONS: The new model using SAPS II and LOD and their evolution during the first calendar days has good discrimination and calibration properties. We propose its use for benchmarking and evaluating the over-risk of death associated with ICU-acquired nosocomial infections.

APACHE↗
PubMed2001

Long-term-impaired expression of nuclear factor-kappa B and I kappa B alpha in peripheral blood mononuclear cells of trauma patients.

Nuclear factor (NF)-kappa B expression and dimer characteristics were studied in peripheral blood mononuclear cells (PBMCs) of major-trauma patients and healthy controls. Analysis of PBMCs on days 1, 3, 5, and 10 after trauma revealed that expression of both p65p50 heterodimers and p50p50 homodimers was significantly reduced compared with that in controls. In vitro lipopolysaccharide (LPS) stimulation of PBMCs induced NF-kappa B translocation. However, throughout the survey, p65p50 activation remained significantly lower in trauma patients than in controls. After LPS stimulation in vitro, the p65p50/p50p50 ratio was significantly lower in PBMCs from trauma patients than from healthy controls. The ex vivo expression of I kappa B alpha was higher in PBMCs of controls than of trauma patients. LPS did not induce I kappa B expression in PBMCs from trauma patients, but strong induction was obtained with staphylococci, suggesting that this defect is not universal and depends on the nature of the activating signal. Although no direct correlation was found between levels of interleukin-10 or transforming growth factor-beta and NF-kappa B, these immunosuppressive cytokines were significantly elevated in trauma patients by 10 days after admission. The long-term low-basal and LPS-induced nuclear translocation of NF-kappa B recalled long-term immunoparalysis observed in patients with severe inflammatory stress such as trauma.

Adolescent↗
PubMed2001

[Nosocomial pneumopathy acquired under mechanical ventilation. Suspicion criteria, bacteriologic diagnosis, and remission criteria].

In intensive care patients, pneumonia acquired under ventilatory assistance is the second most frequent nosocomial infection after urinary tract infection. Duration of ventilatory assistance and stay in the intensive care unit are both increased in this leading cause of death due to nosocomial infection. A large number of studies and national and international consensus conferences have been devoted to determining precise criteria leading to clinical suspicion of pneumonia acquired under ventilatory assistance and the appropriate elements for bacteriological diagnosis. The criteria retained in these different studies are neither precise nor reproductable. Based on data in the literature and our their clinical experience the members of the Outcomerea association constituted working groups to elaborate a set of guidelines that could be applied in routine clinic in response to three questions: 1) what criteria are suggestive of pneumonia acquired under ventilatory assistance, 2) what bacteriological tools are needed to confirm diagnosis, 3) how and why should cure be defined. We present a review of the literature and the conclusions of the working groups.

Cross Infection↗
PubMed2000

[Impact of an information booklet on patient satisfaction in anesthesia].

OBJECTIVE: The aim of this study was to evaluate the satisfaction of adult surgical patients before and after an information booklet concerning anaesthetic techniques and complications, and postoperative management has been proposed during preanaesthetic visits. STUDY DESIGN: Survey. METHOD: Three surveys have been performed using an anonymous questionnaire of 25 items with graduated answers (very good, good, bad, very bad, no opinion) concerning patient satisfaction on structure, physician behavior, information and well being. As the results of the first two surveys were not significantly different, an information booklet was proposed to patients during preanaesthetic visits, then a third survey ("After") was realized. The results of this survey were compared to the combined results of the first two surveys ("Before"). RESULTS: In the "before" survey, 60 to 76% of the patients were satisfied (very good and good) of the information delivered during preanaesthetic visits. The proportion of patients satisfied of the information concerning anaesthetic techniques, transfusion and recovery were significantly higher in the "after" survey (P < 0.05). CONCLUSION: An information booklet on anaesthesia increases patient satisfaction on information provided during preanaesthetic visits.

Adult↗
PubMed2000

Short-term effect of inhaled nitric oxide and prone positioning on gas exchange in patients with severe acute respiratory distress syndrome.

OBJECTIVE: To compare the short-term effects of inhaled nitric oxide (NO) and prone positioning in improving oxygenation in acute respiratory distress syndrome (ARDS). METHODS: Charts of consecutive ARDS patients (lung injury score >2) during a 2-yr period, tested for both inhaled NO and prone positioning efficacy were retrospectively reviewed. Variations in the Pao2/Fio2 ratio induced by inhaled NO and prone positioning were evaluated. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients (age, 42+/-17 yrs) were included. Simplified Acute Physiology Score II was 45+/-14. Mortality rate in the intensive care unit was 63%. The causes of ARDS were pneumonia (n = 14), extra-lung infection (n = 5), and noninfectious systemic inflammatory response syndrome (n = 8). Lung injury score was 2.7+/-0.3. At baseline, before the initiation of inhaled NO, the Pao2/Fio2 ratio was 97+/-46 torr and before prone positioning, 92+/-26 torr. Variations in the Pao2/Fio2 ratio were lower at start of NO therapy (11+/-4 ppm) than that observed at prone positioning initiation (23+/-31 vs. 62+/-78 torr, p<.05). An increase in variations in the Pao2/Fio2 ratio of >15 torr was associated with prone positioning in 16 patients (59%) and with NO inhalation in 13 patients (48%) (not significant). An increase in variations in the Pao2/Fio2 ratio of >15 torr was associated with both techniques in only six patients (22%). There was no correlation between the response to prone positioning and the response to inhaled NO (r2 = .005; p = .73). CONCLUSIONS: Prone positioning improves hypoxemia significantly better than does inhaled NO. The response to one technique is not predictive of the response to the other technique.

APACHE↗
PubMed2000

Nuclear factor-kappaB activation in mouse lung lavage cells in response to Streptococcus pneumoniae pulmonary infection.

OBJECTIVES: To assess the state and activation kinetics of the nuclear transcription regulatory protein nuclear factor-kappB (NF-kappaB) in lung lavage cells in a murine pneumococcal pneumonia model and to determine how the virulence of the infecting organisms altered the activation state of NF-kappaB. DESIGN: Experimental, comparative study of three Streptococcus pneumoniae strains that induced three distinct pulmonary diseases. SETTING: Experimental laboratory in a university-based medical center. SUBJECTS: Female BALB/cby mice, 8-10 wks of age. INTERVENTIONS: We randomly divided the mice into the following five groups: a) the control group; b) animals infected by virulent encapsulated S. pneumoniae P4241 strain; c) animals infected by avirulent encapsulated S. pneumoniae P15986 strain; d) animals infected by avirulent unencapsulated S. pneumoniae R6 strain; e) animals infected by virulent lysed S. pneumoniae P4241 strain. Animals were anesthetized and infected by intratracheal delivery of 4 x 10(5) colony-forming units (CFU) of S. pneumoniae per mouse or bacterial components equivalent to 4 x 10(5) CFU for lysed S. pneumoniae challenge. After intratracheal challenge with virulent encapsulated strain P4241, mice developed acute pneumonia, became bacteremic, and died within 3 to 5 days. None of the mice infected with the avirulent encapsulated strain P15986 or the avirulent unencapsulated strain R6 died. After collection of lung lavage cells and nuclear extraction, NF-kappaB activation was determined 1 hr, 4 hrs, 6 hrs and 24 hrs after pneumococcal infection. At the same time, pulmonary and blood clearance, bronchoalveolar lavage cells population, and tumor necrosis factor-alpha production were assessed (six mice per time point). MEASUREMENTS AND MAIN RESULTS: NF-kappaB was constitutively expressed within nuclear extracts of lung lavage cells from uninfected control mice. A significant increase in NF-kappaB activation was detected within 1 hr after injection of virulent lysed S. pneumoniae P4241 strain (bacterial components equivalent to 4 x 10(5) CFU), and was still present 24 hrs after the injection. After live pneumococcal challenge, significant NF-kappaB activation was detected within 4 hrs with a peak at 24 hrs. Responses to all three strains (P4241, P15986 and R6) were time-dependent (p < .0001), as NF-kappaB activation gradually increased during the first 24 hrs. Moreover, compared with the control uninfected mice, the intensity of the retarded KB oligonucleotide, as determined by densitometry, was increased approximately four- to five-fold and seven-fold in reactions containing nuclear extracts isolated 24 hrs after infection with the avirulent strains P15986 or R6 and the virulent strain P4241, respectively. With the virulent strain P4241, responses were significantly stronger than with the avirulent strains P15986 and R6 (p < .01). Responses were of similar order with avirulent strains P15986 and R6 (p > .05). CONCLUSION: Pulmonary infection by S. pneumoniae induced delayed and time-dependent activation of NF-kappaB in mouse lung lavage cells. The degree of NF-kappaB activation in lung lavage cells correlated with the virulence of the infecting organisms. Our results suggest that the more severe the infection, the higher the rise in NF-kappaB.

Animals↗
PubMed2000

NF-kappaB regulatory mechanisms in alveolar macrophages from patients with acute respiratory distress syndrome.

Activation of the nuclear regulatory factor NF-kappaB occurs in the lungs of patients with the acute respiratory distress syndrome (ARDS) and may contribute to the increased expression of immunoregulatory cytokines and other proinflammatory mediators in this setting. Because of the important role that NF-kappaB activation appears to play in the development of acute lung injury, we examined cytoplasmic and nuclear NF-kapppaB counterregulatory mechanisms, involving IkappaB proteins, in alveolar macrophages obtained from 7 control patients without lung injury and 11 patients with established ARDS. Cytoplasmic levels of the NF-kappaB subunits p50, p65, and c-Rel were significantly decreased in alveolar macrophages from patients with ARDS, consistent with enhanced migration of liberated NF-kappaB dimers from the cytoplasm to the nucleus. Cytoplasmic and nuclear levels of IkappaBalpha were not significantly altered in alveolar macrophages from patients with established ARDS, compared with controls. In contrast, nuclear levels of Bcl-3 were significantly decreased in patients with ARDS compared with controls (P = 0.02). No IkappaBgamma, IkappaBbeta, or p105 proteins were detected in the cytoplasm of alveolar macrophages from control patients or patients with ARDS. The presence of activated NF-kappaB in alveolar macrophages from patients with established ARDS implies the presence of an ongoing stimulus for NF-kappaB activation. In this setting, appropriate counterregulatory mechanisms to normalize nuclear levels of NF-kappaB and to suppress NF-kappaB-mediated transcription, such as increased cytoplasmic and nuclear IkappaBalpha levels or decreased Bcl-3 levels, appeared to be induced. Nevertheless, even though counterregulatory mechanisms to NF-kappaB activation are activated in lung macrophages of patients with ARDS, NF-kappaB remains activated. These results suggest that fundamental abnormalities in transcriptional mechanisms involving NF-kappaB and important in the inflammatory response occur in the lungs of patients with ARDS.

B-Cell Lymphoma 3 Protein↗
PubMed2000

Relationship between capsular type, penicillin susceptibility, and virulence of human Streptococcus pneumoniae isolates in mice.

We examined the relationship between penicillin susceptibility, peritoneal virulence in Swiss mice, and capsular type in a selection of 122 clinical Streptococcus pneumoniae isolates belonging to 24 serotypes. Regardless of the serotype, all 32 virulent strains were susceptible to penicillin, and all 41 strains with diminished susceptibility or resistance to penicillin were avirulent. The remaining 49 strains were both susceptible to penicillin and avirulent, irrespective of the serotype. On the basis of their capsular type and pathogenic behavior, strains fell into one of four groups. In the group consisting of serotypes 1, 3, and 4 (n = 16), strains were predominantly virulent (81.3%), and all were penicillin susceptible. In the serotype 6 group (n = 32), the frequency of virulence was significantly lower (34.4 versus 81.3%, P = 0.002), and strains were predominantly penicillin susceptible (71.9%). In the group composed of serotypes 9, 14, 19, and 23 (n = 50), all strains were avirulent, and 56% had decreased susceptibility (n = 12) or resistance to (n = 16) penicillin. The fourth group was heterogenous, as it pooled 24 strains of 15 different serotypes; in this group the frequency of virulence was 33.3%, and strains were predominantly penicillin susceptible (83.3%). These data point to a complex relationship between penicillin susceptibility and virulence in mice but do not entirely separate these characteristics from the role of the capsular type. The possibility that the mechanisms conferring penicillin resistance are related to those leading to a loss of virulence is supported by these findings.

Animals↗
PubMed2000

NF-kappaB expression in mononuclear cells of patients with sepsis resembles that observed in lipopolysaccharide tolerance.

The expression of NF-kappaB was studied in freshly isolated peripheral blood mononuclear cells (PBMC) of patients with severe sepsis and major trauma. The expression of p65p50 heterodimer, the active form of NF-kappaB, was significantly reduced for all patients as compared with control subjects. The p50p50 homodimer, an inhibitory form of NF-kappaB, was reduced in the survivors of sepsis and in patients with trauma. Subsequent in vitro stimulation of PBMC with lipopolysaccharide (LPS) did not induce further NF-kappaB nuclear translocation: the survivors of sepsis and trauma patients showed low expression of both p65p50 and p50p50, whereas nonsurvivors of sepsis showed a predominance of the inactive homodimer and a low p65p50/p50p50 ratio when compared with control subjects. In the later group of patients there was a reverse correlation between plasma IL-10 levels and the p65p50/p50p50 ratio after in vitro LPS stimulation (r = -0.8, p = 0.04). The reduced expression of nuclear NF-kappaB was not due to its inhibition by IkappaBalpha, as very low expression of IkappaBalpha, as well as low levels of p65 and p50 were found in the cytoplasm of PBMC from patients with sepsis and trauma when compared with control subjects. These results demonstrate that upon LPS activation, PBMC of patients with systemic inflammatory response syndrome show patterns of NF-kappaB expression that resemble those reported during LPS tolerance: global down-regulation of NF-kappaB in survivors of sepsis and trauma patients and the presence of large amounts of the inactive homodimer in the nonsurvivors of sepsis.

Adolescent↗
PubMed1999

[Current microbiologic problems. Pulmonary infection by Streptococcus pneumoniae. Current physiopathological aspects].

STILL A SERIOUS DISEASE: Despite advances in antibiotic therapy, and despite the emergence of beta-lactam-resistant strains, mortality of pneumococcal pneumonia has remained relatively unchanged. The pathogenicity of a pneumococcal strain results from an interaction between a specific host with its own capacity to "resist or yield" to the multiple virulence factors intrinsic to each S. pneumoniae strain. ROLE OF THE CAPSULE: The capsule is the pneumococci's principal arm of resistance against the host's defense systems. There is a wide variability depending on the capsule serotype. Inversely, the capsule plays no role in triggering the inflammatory reaction which is secondary to substances released from the bacterial wall such as teichoic acid and peptidoglycan. HOST RESPONSE: The molecular mechanisms of cellular activation and induction of proinflammatory cytokines triggered by S. pneumoniae follow similar pathways which are different from those for endotoxin triggered by Gram negative bacteria. PERSPECTIVES: A better understanding of the clinical expression, distinguishing simple nasopharyngeal carriage from bacterial pneumonia should lead to the design of new therapeutic agents which will reduce the capacity of certain S. pneumoniae strains to invade the host and trigger deleterious inflammatory reactions.

Humans↗
PubMed1999

[Organ procurement from cardiac arrest donors: outcome of kidney grafts and recommendations].

OBJECTIVES: To compare literature data with results obtained with organs procured from donors who died from cardiac arrest and to make proposals for this mode of organ procurement in France. METHODS: Over the last 10 years, 10 organ donors (2%) among a series of 486 donors in a state of brain death, had died of cardiac arrest. The arrest were perfused with double-balloon catheters. The outcome of the subsequent kidney grafts was compared with data in the literature. RESULTS: Fifteen of the 18 kidneys from cardiac arrest donors were functioning 1 month after implantation compared with 17 of the 20 kidneys from braindeath donors with beating hearts. The rate of acute tubular necrosis was 55% in the cardiac arrest kidneys and 40% in the beating-heart kidneys. Serum creatinine at 1 yeart was 145 +/- 69 mumol/l 17 +/- 29 mumol/l respectively. DISCUSSION: These results and those reported in the literature demonstrate that kidney procurement from cardiac arrest donors is feasible. If intensive care and surgery units are well organized, this type of organ procurement could provide a larger number of organs for transplantation. Emergency teams must be available for preparing and transferring the organs.

Cadaver↗