ABSTRACT
Until now, microwave plasmas could be ignited in small capillary tubes (inner diameter less than 1 mm) by generating surface waves propagating along their dielectric surfaces using mainly surfatron launchers or stripline-based launchers, such as "split-ring resonators." This work presents a novel launcher, which is called the "striplastron," because it is halfway between surfatrons and stripline launchers. It is a circular stripline directly excitated by a microcoaxial cable. Compared with the surfatron, it is smaller and the part of the plasma hidden by the launcher is limited to its thickness (â¼1-2 cm). Moreover, its frequency response presents an intense and large resonance. Eventually, its geometry could allow the simultaneous ignition of several microplasmas in capillaries arranged in parallel, which could be very interesting for applications, such as the use of multi-tube microplasmas as metamaterials.
ABSTRACT
OBJECTIVES: Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. METHODS: Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. RESULTS: The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. CONCLUSION: PID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults.
Subject(s)
Bacteremia/etiology , Bacteremia/immunology , Complement System Proteins/deficiency , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/diagnosis , Meningitis, Bacterial/etiology , Meningitis, Bacterial/immunology , Adolescent , Adult , Female , Humans , Immunologic Factors/deficiency , Male , Mass Screening/methods , Prevalence , Retrospective Studies , Young AdultABSTRACT
OBJECTIVE: The clinical characteristics and prognosis of patients treated for Candida peritonitis (CP) were compared according to the type of systemic antifungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection. METHODS: Patients in intensive care units (ICU) treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for unconfirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF. RESULTS: In all, 279 patients were evaluated (43.4% EAF/nonCP, 29.7% EAF/CP and 25.8% TAF patients). At SAT initiation, the severity of illness was similar among EAF/nonCP and EAF/CP patients, lower among TAF patients (median Simplified Acute Physiology Score II (SAPS II) 49 and 51 versus 35, respectively; p 0.001). Candida albicans was involved in 67%, Candida glabrata in 15.6%. All strains were susceptible to echinocandin; 84% to fluconazole. Echinocandin was administered to 51.2% EAF/nonCP, 49% EAF/CP and 40% TAF patients. At day 28, 72%, 76% and 75% of EAF/nonCP, EAF/CP and TAF patients, respectively, were alive. An increased mortality was observed in patients with a Sequential Organ Failure Assessment (SOFA) score <7 if SAT was delayed by ≥6 days (p 0.04). Healthcare-associated CP (OR 3.82, 95% CI 1.52-9.64, p 0.004), SOFA ≥8 at ICU admission (OR 2.61, 95% CI 1.08-6.34; p 0.03), and SAPS II ≥45 at SAT initiation (OR 5.08, 95% CI 1.04-12.67; p 0.001) impacted the 28-day mortality. CONCLUSIONS: In summary, only 56.6% of ICU patients receiving SAT had CP. Most strains were susceptible to SAT. A similar 28-day mortality rate was observed among groups; the late administration of SAT significantly worsened the prognosis of patients with less severe CP.
Subject(s)
Antifungal Agents/therapeutic use , Candida , Candidiasis/drug therapy , Candidiasis/microbiology , Intensive Care Units , Peritonitis/drug therapy , Peritonitis/microbiology , Aged , Antifungal Agents/pharmacology , Candidiasis/diagnosis , Candidiasis/mortality , Comorbidity , France , Humans , Middle Aged , Odds Ratio , Peritonitis/diagnosis , Peritonitis/mortality , Prospective Studies , ROC Curve , Risk Factors , Severity of Illness Index , Treatment OutcomeABSTRACT
OBJECTIVE: We had for aim to describe the identification and management of a 14-clonal carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak, following admission of a known CRAB-infected patient in an ICU. METHODS: We reviewed the carriers' files and outbreak management procedures. RESULTS: The index patient was admitted with strict isolation precautions. The outbreak started 2 months after his discharge. It persisted despite reinforcement of strict isolation precautions, staff and patient cohorting, and extensive environmental decontamination including 2 rounds of routine terminal cleaning and disinfection or 1 round of cleaning and disinfection followed by hydrogen peroxide treatment. A second epidemic peak, after 4 weeks without any case, led to another wide environmental sampling and decontamination rounds. The source of the CRAB outbreak was suspected to be the blood pressure cuffs Velcro. Switching to cuffs submersible in a disinfectant stopped the outbreak. CONCLUSIONS: CRAB outbreaks are difficult to manage and sources of persistent colonization can be unexpected.
Subject(s)
Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Cross Infection/microbiology , Decontamination/methods , Disease Outbreaks , Intensive Care Units , Sphygmomanometers/microbiology , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter Infections/prevention & control , Acinetobacter baumannii/isolation & purification , Adult , Anal Canal/microbiology , Anti-Bacterial Agents/therapeutic use , Carbapenems/therapeutic use , Carrier State/microbiology , Cross Infection/drug therapy , Cross Infection/epidemiology , Cross Infection/prevention & control , Disinfectants , Disinfection , Drug Resistance, Microbial , Equipment Contamination , Equipment and Supplies, Hospital , France/epidemiology , Hospitals, General , Humans , Hydrogen Peroxide , Male , Patient Isolation , Patients' Rooms , Personnel, Hospital , Pharynx/microbiology , Universal PrecautionsABSTRACT
PURPOSE: We assessed factors associated with mortality and complicated course in the case of Clostridium difficile infection (CDI) acquired in the intensive care unit (ICU). METHOD: Retrospective cohort study conducted from 1 January 2002 through 1 January 2012. All patients who acquired CDI in our ICU were included. RESULTS: Thirty-one patients were included. Twenty patients (65 %) had mild colitis, 8 (25 %) moderate colitis, and 3 (10 %) severe colitis. Initial antibiotherapy was metronidazole (n = 30, 97 %) and vancomycin (n = 1, 3 %). Seventeen patients (55 %) experienced at least one complication: failure of initial treatment (n = 16, 52 %), shock (n = 11, 34 %), need for surgery (n = 1, 3 %) or renal replacement (n = 4, 13 %), or death (n = 8, 26 %). Risk factors of ICU mortality were history of corticosteroids prescription, prolonged ICU stay, low serum albumin level, and high Sequential Organ Failure Assessment (SOFA) score at the time of CDI diagnosis. Factors associated with a complicated course were high Simplified Acute Physiology Score (SAPS II), high SOFA score, and low serum albumin level at the time of CDI onset. CONCLUSION: Risk factors of poor outcome in patients with CDI acquired in the ICU are different from those in the general population suffering from CDI. The implementation of treatment algorithms taking into account these factors may reduce complication rates in this specific population.
Subject(s)
Clostridioides difficile/isolation & purification , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Colitis/epidemiology , Colitis/microbiology , Adult , Aged , Aged, 80 and over , Clostridium Infections/mortality , Clostridium Infections/pathology , Cohort Studies , Colitis/mortality , Colitis/pathology , Female , Humans , Intensive Care Units , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
Current diagnostic methods allow microbial identification in 50% of patients admitted with severe community-acquired pneumonia (CAP). Guidelines derived from epidemiological data help physicians to start empirical antimicrobial therapy. Definitive microbial diagnosis is useful to guide further pathogen-directed therapy. Blood cultures, cultures of respiratory specimens and urine antigen tests are recommended to determine the causative bacterial pathogen. Positive blood cultures range from 15 to 25% of CAP patients according to severity. Whether sputum specimens represent or not lower respiratory secretions determines its accuracy in CAP microbial diagnosis. In intubated patients, endotracheal aspirates are often of interest. Detection of positive pneumococcal or legionella urinary antigen is often associated with CAP severity. The sensitivity of this test is not decreased in patients who have received antibiotics prior to sampling. Viral pneumonia account for 10 to 40% of severe CAP. Nasal swabs are recommended for influenza identification using polymerase chain reaction (PCR) in order to deliver oseltamivir treatment. In the emergency department, atypical pneumonia serology is less useful than respiratory specimens obtained using fiberoptic bronchoscopy. Serum PCR to diagnose bacterial CAP is not superior to the other usual methods.
ABSTRACT
We report on a self-guided microwave surface-wave induced generation of ~60 µm diameter and 6 cm-long column of argon-plasma confined in the core of a hollow-core photonic crystal fiber. At gas pressure of 1 mbar, the micro-confined plasma exhibits a stable transverse profile with a maximum gas-temperature as high as 1300 ± 200 K, and a wall-temperature as low as 500 K, and an electron density level of 10¹4 cm⻳. The fiber guided fluorescence emission presents strong Ar⺠spectral lines in the visible and near UV. Theory shows that the observed combination of relatively low wall-temperature and high ionisation rate in this strongly confined configuration is due to an unprecedentedly wide electrostatic space-charge field and the subsequent ion acceleration dominance in the plasma-to-gas power transfer.
ABSTRACT
Adult onset Still's disease is an inflammatory disorder characterized by daily spiking high fevers, arthritis and an evanescent rash. It is a rare disease of unknown aetiology and can be life-threatening. We present a case of adult onset Still's disease associated with myocarditis requiring the use of invasive ventilation, in which the patient responded well to systemic steroids.
Subject(s)
Myocarditis/complications , Still's Disease, Adult-Onset/etiology , Adrenal Cortex Hormones/therapeutic use , Adult , Anti-Inflammatory Agents/therapeutic use , Female , Humans , Magnetic Resonance Imaging , Myocarditis/drug therapy , Respiration, Artificial , Still's Disease, Adult-Onset/diagnosis , Still's Disease, Adult-Onset/drug therapyABSTRACT
PURPOSE: To report the clinical characteristics and prognosis of prosthetic joint infections (PJIs) in Intensive care units (ICUs). METHODS: Forty-one patients consecutively admitted to ICUs for PJIs between January 2004 and June 2011 were included in a retrospective case series. RESULTS: A majority of patients (73 %) had severe underlying disease. Acute infection affected 26 patients (63 %). Blood cultures were positive in 16 patients (39 %). Staphylococcus species were the most commonly implicated causative organisms (n = 36, 88 %). The surgical strategy was two-stage replacement in 25 cases (61 %). The surgical procedure leading to ICU admission was mainly prosthesis removal with spacer implantation (n = 13, 32 %). Initial antibiotherapy was a broad-spectrum beta-lactam antibiotic combined with a glycopeptide, linezolid, or daptomycin in 26 cases (63 %). Mortality in the ICU was 20 %. In nonsurvivors, diabetes, acute infection, and American Society of Anesthesiologists (ASA) score >3 were more frequent. The distribution of surgical strategies and procedures was not statistically different in survivors and nonsurvivors. The proportion of patients treated with antibiotherapy adjusted according to previous microbiological findings was higher in nonsurvivors (50 vs. 12 %, p = 0.02). CONCLUSIONS: In our case series of critically ill patients suffering from PJI, factors associated with a poor outcome were diabetes mellitus, ASA score >3, and acute infection. Surgical strategies and surgical procedures had no significant impact on the ICU mortality. Adjustment of initial antibiotherapy according to previous microbiological findings should be made with caution.
Subject(s)
Critical Illness/mortality , Joint Diseases/mortality , Prosthesis-Related Infections/mortality , Acute Disease , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Device Removal , Diabetes Mellitus/microbiology , Female , Humans , Intensive Care Units , Joint Diseases/drug therapy , Joint Diseases/microbiology , Male , Middle Aged , Prognosis , Prostheses and Implants , Prosthesis-Related Infections/drug therapy , Prosthesis-Related Infections/microbiology , Retrospective Studies , Severity of Illness Index , Staphylococcus/isolation & purification , Synovial Fluid/microbiology , Treatment OutcomeABSTRACT
Pharmacodynamic studies report on the rapid bactericidal activity of aminoglycosides, conferring them as being of theoretical interest for bacteraemia treatment. We assessed this issue in a retrospective study of patients with intensive care unit (ICU)-acquired bacteraemias. To determine the impact of aminoglycosides in antimicrobial combination on the outcome of patients with bacteraemia, we performed a monovariate analysis and a logistic regression analysis comparing patients treated with or without aminoglycosides. Forty-eight bacteraemias in 48 patients were included. Eighteen patients received aminoglycosides. Baseline characteristics as well as adaptation and adequation of antibiotherapy did not differ in patients who did or did not receive aminoglycosides. Patients who received aminoglycosides had longer time alive away from the ICU (11.3 ± 8.9 (10 [0-20]) vs. 3.2 ± 6.6 (0 [0-2] days; p = 0.002) and free from mechanical ventilation (12.5 ± 9.3 (14 [0-21] vs. 5.5 ± 9.2 (0 [0-10] days; p = 0.02) on day 28. The ICU mortality was 16% in the aminoglycoside group versus 46% (p = 0.03). In the multivariate analysis, patients treated with aminoglycosides were 6 times less likely to die than those treated without aminoglycosides (confidence interval [CI] = [1.3-28.9]; p = 0.02). Our study supports the hypothesis that combination short-term antibiotherapy with an aminoglycoside for ICU-acquired bacteraemias could increase survival.
Subject(s)
Aminoglycosides/therapeutic use , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Cross Infection/drug therapy , Aged , Drug Therapy, Combination/methods , Female , Humans , Intensive Care Units , Male , Middle Aged , Survival Analysis , Treatment OutcomeABSTRACT
Prosthetic vascular graft infection is a rare but very severe complication with a high death rate. Its optimal management requires appropriate surgical procedures combined with adequate antimicrobial treatment in reference center. The authors wanted to focus on the management of prosthetic vascular graft infection and define the clinical, microbiological, biological, and radiological criteria of vascular graft infection. Complementary investigations, although these are small series, include CT scan, the gold standard for the diagnosis of acute infection with a sensitivity and specificity reaching 100%, but decreased to 55% in case of chronic infection. More recently, PET-scanning was studied and yielded good results in chronic infections (sensitivity 98%, specificity 75.6%, positive predictive value 88.5%, and negative predictive value 84.4%). Managing prosthetic vascular graft infection, as with the orthopedic and vascular infections, requires replacing the vascular prosthesis. There is no correlation between the microbiological data and the location or type of vascular infection. Thus, the postoperative intravenous antibiotherapy should be bactericidal with a broad-spectrum. After obtaining intra-operative microbiological results, de-escalation therapy must include at least one anti-adherence agent, such as rifampicin in staphylococcal infections.
Subject(s)
Bacterial Infections/diagnosis , Bacterial Infections/drug therapy , Blood Vessel Prosthesis/adverse effects , Diagnostic Imaging/methods , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/drug therapy , Aftercare , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Adhesion/drug effects , Bacterial Infections/blood , Bacterial Infections/diagnostic imaging , Bacterial Infections/surgery , Combined Modality Therapy , Contrast Media , Device Removal , Disease Management , Drug Resistance, Microbial , Humans , Magnetic Resonance Angiography , Positron-Emission Tomography , Predictive Value of Tests , Prosthesis-Related Infections/blood , Prosthesis-Related Infections/surgery , Reoperation , Sensitivity and Specificity , Tomography, X-Ray Computed , Ultrasonography, DopplerABSTRACT
Prosthetic vascular graft infection (PVGI) is a devastating complication, with a mortality rate of up to 75%, which is especially caused by aortic graft infection. The purpose of this study was to evaluate factors associated with in-hospital mortality of patients with definite graft infection, and with long-term outcome. We reviewed medical records of 85 patients treated for PVGIs defined by positive bacterial culture of intraoperative specimens or blood samples, and/or clinical, biological and radiological signs of infection. In-hospital patient mortality was defined as any death occurring during the initial treatment of the graft infection. Cure was defined as the absence of evidence of relapsing infection during long-term follow-up (≥1 year). Eighty-five patients (54 aortic and 31 limb graft infections) treated by surgical debridement and removal of the infected prosthesis (n=41), surgical debridement without removal of prosthesis (n=34) or antimicrobial treatment without surgery (n=10) were studied. The only microbiological difference observed between patients with early (occurring within 4 months after surgery) vs. late PVGI and between those with aortic vs. limb PVGI was the incidence of PVGI caused by Staphylococcus aureus, which was greater in patients with limb PVGI. Overall cure was observed in 93.2% of 59 patients with a follow-up of a minimum of 1 year. Overall in-hospital mortality was 16.5% (n=14). Two variables were independently associated with mortality: age >70 years (OR 9.1, 95% CI 1.83-45.43, p 0.007) and aortic graft infection (OR 5.6, 95% CI 1.1-28.7, p 0.037).
Subject(s)
Blood Vessel Prosthesis Implantation/adverse effects , Gram-Negative Bacteria/pathogenicity , Gram-Negative Bacterial Infections/mortality , Gram-Positive Bacterial Infections/mortality , Prosthesis-Related Infections/mortality , Age Factors , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , Bacteremia/microbiology , Bacteremia/mortality , Blood Vessel Prosthesis/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Female , Follow-Up Studies , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/microbiology , Gram-Positive Bacteria/isolation & purification , Gram-Positive Bacteria/pathogenicity , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/microbiology , Hospitals , Humans , Incidence , Male , Medical Records , Middle Aged , Prognosis , Prospective Studies , Prosthesis-Related Infections/drug therapy , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/pathology , Recurrence , Risk Factors , Treatment OutcomeABSTRACT
Information on the species causing Candida peritonitis, their in vitro susceptibility, antifungal strategies in this setting and patient outcome is still scarce. AmarCand was a prospective, non-interventional study in 271 adult intensive-care unit (ICU) patients with proven invasive Candida infection who received systemic antifungal therapy (France, 2005-2006). Of these ICU patients, 93 (median age 65 years, simplified acute physiology score II 52) had Candida peritonitis, including 73 nosocomial peritonitis, 53 concomitant bacterial peritoneal infections and 26 candidaemias. Candida species were C. albicans (n = 63/108 isolates, 58%), C. glabrata (n = 22, 20%), C. krusei (n = 9), C. kefyr (n = 5), C. parapsilosis (n = 3), C. tropicalis (n = 3), C. ciferii (n = 2) and C. lusitaniae (n = 1). Of tested isolates, 28% were fluconazole-resistant or susceptible dose-dependent (C. albicans 3/32, C. glabrata 9/14, C. krusei 4/4). Empiric antifungal treatment was started 1 day (median) after peritonitis diagnosis, with fluconazole (n = 2 patients), caspofungin (n = 12), voriconazole (n = 3), amphotericin B (n = 2), or a combination (n = 4). Following susceptibility testing, empiric antifungal treatment was judged inadequate in 9/45 (20%) patients and modified in 30 patients (fluconazole was replaced by caspofungin (n = 14) or voriconazole (n = 4)). Mortality in ICU was 38% (35/93) and was not influenced by type of Candida species, fluconazole susceptibility, time to treatment, candidaemia, nosocomial acquisition, or concomitant bacterial infection. No specific factors for death were identified. In summary, a high proportion of fluconazole-resistant or susceptible dose-dependent strains was cultured. These results confirm the high mortality rates of Candida peritonitis and plead for additional investigation in this population. Antifungal treatment for severe cases of Candida peritonitis in ICU patients remains the standard care.
Subject(s)
Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Peritonitis/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antifungal Agents/pharmacology , Candida/classification , Candida/drug effects , Candida/isolation & purification , Candidiasis/microbiology , Candidiasis/mortality , Cross Infection/drug therapy , Cross Infection/microbiology , Cross Infection/mortality , Female , France , Humans , Intensive Care Units , Male , Microbial Sensitivity Tests , Middle Aged , Peritonitis/microbiology , Peritonitis/mortality , Prospective Studies , Treatment Outcome , Young AdultABSTRACT
Numerous guidelines are available to guide empirical antimicrobial therapy (EAT) in acute bacterial meningitis (ABM) patients. We analysed prognosis factors and compliance to the Infectious Diseases Society of America (IDSA) guidelines in ABM patients requiring stay in an intensive care unit (ICU). A 10-year retrospective study, using prospectively collected data, in 82 ABM patients admitted to a 16-bed university-affiliated French ICU was undertaken. Seventeen patients (20.7%) died during ICU stay. Multivariate analysis isolated four factors associated with in-ICU death: alcoholism (P = 0.007), acute kidney injury (P = 0.006), age >60 years (P = 0.006) and ICU admission for neurological failure (P = 0.01). Causative pathogens were isolated for 62 (75.6%) patients, including 29 pneumococci, 14/28 of which were non-susceptible to penicillin. No characteristics, particularly recent hospitalisation and/or antibiotic delivery, was associated with penicillin susceptibility. Compliance to IDSA guidelines was 65%. Non-compliance concerned to be essentially the non-delivery or low dosage of vancomycin. Treatment compatible with IDSA guidelines was associated with a decreased ICU mortality in univariate (61.5% survival vs. 35.3%, P = 0.05) but not in multivariate analysis. In-ICU mortality associated with ABM remains high. Prognosis factors are related to the severity of disease or underlying conditions. Penicillin non-susceptible Streptococcus pneumoniae can occur without any of the usual predisposing factors.
Subject(s)
Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Critical Care/methods , Critical Care/trends , Guideline Adherence/statistics & numerical data , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Bacteria/isolation & purification , Community-Acquired Infections/microbiology , Community-Acquired Infections/mortality , Female , France , Humans , Male , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/mortality , Middle Aged , Prognosis , Prospective Studies , Treatment Outcome , Young AdultABSTRACT
We performed a single-blind, randomized phase 1 trial of the long synthetic peptide (LSP) of merozoite surface protein-3 (MSP3) in adults living in Burkina Faso. Thirty eligible volunteers were randomized to receive either the MSP3-LSP candidate vaccine or tetanus toxoid vaccine as a control. A dose of each vaccine was administered on days 0, 28 and 112 and the vaccine was formulated with aluminium hydroxide. Humoral immune responses were assessed by ELISA at days 0, 28, 56, 112, 140, 252 and 365 and cell-mediated immune responses by lymphoproliferation assay and by ELISA on days 0, 56 and 140. IgG responses to four peptides of MSP3 were similar in both vaccine groups. Higher IgG concentrations were recorded after the beginning of malaria high transmission season in both vaccine groups. The lymphocyte proliferation and the production of IFN-gamma in response to stimulation with the four overlapping peptides increased following vaccination in the MSP3-LSP vaccine group, but did not change appreciably in the control group. In contrast to natural infection, MSP3-LSP did not boost humoral responses to the four overlapping peptides of MSP3 to any detectable degree in our semi-immune adult. MSP3-LSP may be more immunogenic in young children with little or no acquired immunity.
Subject(s)
Antigens, Protozoan/immunology , Leukocytes, Mononuclear/immunology , Malaria Vaccines/immunology , Malaria, Falciparum/prevention & control , Peptide Fragments/immunology , Vaccination , Adolescent , Adult , Amino Acid Sequence , Antibodies, Protozoan/blood , Antigens, Protozoan/administration & dosage , Burkina Faso , Cells, Cultured , Humans , Immunoglobulin G/blood , Interferon-gamma/biosynthesis , Leukocytes, Mononuclear/metabolism , Malaria Vaccines/administration & dosage , Male , Molecular Sequence Data , Peptide Fragments/administration & dosage , Peptides/administration & dosage , Peptides/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunologySubject(s)
Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/microbiology , Mitral Valve Insufficiency/microbiology , Acute Disease , Adult , Aggregatibacter actinomycetemcomitans/isolation & purification , Anti-Bacterial Agents/therapeutic use , Cardiobacterium/isolation & purification , Combined Modality Therapy , Eikenella corrodens/isolation & purification , Endocarditis, Bacterial/complications , Female , Haemophilus/isolation & purification , Humans , Kingella kingae/isolation & purification , Mitral Valve/pathology , Mitral Valve/surgery , Mitral Valve Insufficiency/surgery , Young AdultABSTRACT
OBJECTIVE: Comparison of treatments initiated during invasive candidiasis in intensive care units with current French guidelines. STUDY DESIGN: Prospective, observational, French multicenter study (October 2005-May 2006). PATIENTS AND METHODS: Selection of patients with Candida species identification and in vitro antifungal susceptibility determination. The empiric treatments instituted before the microbiologic documentation of infection and the curative treatments instituted after identification of the causative Candida and determination of its susceptibility were collected and compared with treatments proposed by the French clinical practice guidelines (2004) for the management of patients with invasive candidiasis. RESULTS: One hundred and eighty-six patients were studied. Invasive candidiasis was due to fluconazole-resistant or susceptible-dose dependent Candida in 18.3% of patients, without any significant influence of a previous treatment with azoles. Empiric and curative treatments were both in accordance with recommendations for 47% of patients. Recommendations were mainly not respected when proposed therapy was amphotericin B that disappeared from therapeutics used in ICU. Finally, 16.9% of episodes of invasive candidiasis, for which fluconazole was the recommended treatment, were due to fluconazole-resistant or susceptible-dose dependent Candida. CONCLUSION: The support of French ICU physicians to current French guidelines was observed in 47% of cases. The infrequent use of amphotericin B must be emphasized. The nonnegligible incidence of fluconazole-resistant or susceptible-dose dependent Candida sp., particularly in patients without any prior exposition to azole agents, and the inability to predict this resistance should lead to propose a revision of 2004 guidelines.
Subject(s)
Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Intensive Care Units , Adolescent , Adult , Aged , Aged, 80 and over , Female , Guideline Adherence , Humans , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
Neurofibrillary degeneration is often observed in the brain of patients with type 1 myotonic dystrophy (DM1). It consists principally of the aggregation of Tau isoforms that lack exon 2/3 encoded sequences, and is the consequence of the modified splicing of Tau pre-mRNA. In experimental models of DM1, the splicing of several transcripts is modified due to the loss of Muscleblind-like 1 (MBNL1) function. In the present study, we demonstrate that the MBNL1 protein is also present in the human brain, and consists of several isoforms, as shown by RT-PCR and sequencing. In comparison with controls, we show that the adult DM1 brain exhibits modifications in the splicing of MBNL1, with the preferential expression of long MBNL1 isoforms--a splicing pattern similar to that seen in the fetal human brain. In cultured HeLa cells, the presence of long CUG repeats, such as those found in the DM1 mutation, leads to similar changes in the splicing pattern of MBNL1, and the localization of MBNL1 in nuclear RNA foci. Long CUG repeats also reproduce the repression of Tau exon 2/3 inclusion, as in the human disease, suggesting that their effect on MBNL1 expression may lead to changes in Tau splicing. However, while an overall reduction in the expression of MBNL1 mimics the effect of the DM1 mutation, none of the MBNL1 isoforms tested so far modulates the endogenous splicing of Tau. The modified splicing of Tau thus results from a possibly CUG-mediated loss of function of MBNL1, but not from changes in the MBNL1 expression pattern.