Covering the optical spectrum through collective rare-earth doping of NaGdF4 nanoparticles: 806 and 980 nm excitation routes.

Today, at the frontier of biomedical research, the need has been clearly established for integrating disease detection and therapeutic function in one single theranostic system. Light-emitting nanoparticles are being intensively investigated to fulfil this demand, by continuously developing nanoparticle systems simultaneously emitting in both the UV/visible (light-triggered release and activation of drugs) and the near-infrared (imaging and tracking) spectral regions. In this work, rare-earth (RE) doped nanoparticles (RENPs) were synthesized via a thermal decomposition process and spectroscopically investigated as potential candidates as all-in-one optical imaging, diagnostic and therapeutic agents. These core/shell/shell nanoparticles (NaGdF4:Er3+,Ho3+,Yb3+/NaGdF4:Nd3+,Yb3+/NaGdF4) are optically excited by heating-free 806 nm light that, aside from minimizing the local thermal load, also allows to obtain a deeper sub-tissue penetration with respect to the still widely used 980 nm light. Moreover, these water-dispersed nanoplatforms offer interesting assets as triggers/probes for biomedical applications, by virtue of a plethora of emission bands (spanning the 380-1600 nm range). Our results pave the way to use these RENPs for UV/visible-triggered photodynamic therapy/drug release, while simultaneously tracking the nanoparticle biodistribution and monitoring their therapeutic action through the near-infrared signal that overlaps with biological transparency windows.

Double rare-earth nanothermometer in aqueous media: opening the third optical transparency window to temperature sensing.

Owing to the alluring possibility of contactless temperature probing with microscopic spatial resolution, photoluminescence nanothermometry at the nanoscale is rapidly advancing towards its successful application in biomedical sciences. The emergence of near-infrared nanothermometers has paved the way for temperature sensing at the deep tissue level. However, water dispersibility, adequate size at the nanoscale, and the capability to efficiently operate in the second and third biological optical transparency windows are the requirements that still have to be fulfilled in a single nanoprobe. In this work, these requirements are addressed by rare-earth doped nanoparticles with core/shell-architecture, dispersed in water, whose excitation and emission wavelengths conveniently fall within the biological optical transparency windows. Under heating-free 800 nm excitation, double nanothermometry is realized either with Ho3+-Nd3+ (1.18-1.34 µm) or Er3+-Nd3+ (1.55-1.34 µm) NIR emission band ratios, both displaying equal thermal sensitivities around 1.1% °C-1. It is further demonstrated that, along with the interionic energy transfer processes, the thermometric properties of these nanoparticles are also governed by the temperature dependent energy transfer to the surrounding solvent (water) molecules. Overall, this work presents a novel water dispersible double ratiometric nanothermometer operating in the second and third biological optical transparency windows. The temperature dependent particle-solvent interaction is also presented, which is critical for e.g. future in vivo applications.

Magnetic nanoparticle clusters as actuators of ssDNA release.

One of the major areas of research in nanomedicine is the design of drug delivery systems with remotely controllable release of the drug. Despite the enormous progress in the field, this aspect still poses a challenge, especially in terms of selectivity and possible harmful interactions with biological components other than the target. We report an innovative approach for the controlled release of DNA, based on clusters of core-shell magnetic nanoparticles. The primary nanoparticles are functionalized with a single-stranded oligonucleotide, whose pairing with a half-complementary strand in solution induces clusterization. The application of a low frequency (6 KHz) alternating magnetic field induces DNA melting with the release of the single strand that induces clusterization. The possibility of steering and localizing the magnetic nanoparticles, and magnetically actuating the DNA release discloses new perspectives in the field of nucleic-acid based therapy.

Polymer-hematite nanocomposites: templating effect of commercial ion-exchangers in the growth of size-controlled iron oxide nanoparticles.

The commercially available ion-exchange resin Amberlite IR120 has been used as the stabilizing agent for the preparation of a size controlled nanostructured hematite phase. The employed synthetic approach, based on the loading of Fe3+ by ion exchange and the subsequent treatment with an aqueous base solution, produces a nanocomposite material with a remarkably high content of oxide nanoparticles (iron content = 18.8% w/w, corresponding to 24.9% w/w of Fe2O3). Scanning electron microscopy and energy dispersive X-ray spectroscopy investigation show that the iron distribution is egg-like and parallels the distribution of the sulfonic groups of the ion-exchanger. Transmission electron microscopy characterization reveals that the size of the ferric oxide nanoparticles in the nanocomposites is narrowly distributed in the 4-6 nm range and that it is the same after the first and the fifth ion-exchange-precipitation cycle. Selected area Electron Diffraction (SAED) analysis of the nanostructured oxide after five ion-exchange-precipitation cycles indicates that it is hematite with a distorted structure.

Cross-linked polyvinyl polymers versus polyureas as designed supports for catalytically active M(0) nanoclusters. Part III. Nanometer scale structure of the cross-linked polyurea support EnCat 30 and of the Pd(II)/EnCat 30 and Pd(0)/EnCat 30NP catalysts.

The cross-linked polyurea support EnCat 30, its related macromolecular complex Pd(II)/EnCat 30 and its related Pd(0)/EnCat 30NP nanocomposite are thoroughly investigated with SEM, TEM, ISEC and ESR in the solid state (SEM and TEM) and swollen state in THF (ISEC and ESR). Pd(II)/EnCat 30 and its related Pd(0)/EnCat 30NP are obtained by microencapsulation of palladium acetate in a polyurea framework, which is formed upon hydrolysis/condensation of mixtures of multi-functional oligo-arylisocyanates in dichloroethane. Most remarkably, both Pd(II)/EnCat and Pd(0)/EnCat 30NP turn out to be far more (nano)porous and swellable materials than the blank polyurea matrix (EnCat 30). It is proposed that there is a strong nanostructural effect exerted by Pd(II) species due to its interaction with functional groups (amines stemming from the hydrolysis of the isocyanato groups or ureido groups belonging to the polymer chains) during the growth of the cross-linked polymer framework. As a consequence, the catalytic species in both Pd(II)/EnCat 30 and Pd(0)/EnCat 30NP are much more accessible to molecules diffusing from liquid phases in contact with the materials and, hence, are better catalysts than expected from the morphology of blank polyurea EnCat 30.

[Varicella zoster virus infection after bone marrow transplant. Unusual presentation and importance of prevention]. / Infection par le virus varicelle-zona après greffe de moelle osseuse. Présentations inhabituelles et intérêt de la prophylaxie.

BACKGROUND: Leukemeia and lymphoproliferative disease are associated with a high risk of varicela-zoster virus (VZV) infection. Although infrequent, visceral involvement can be fatal. We report two cases of patients presenting severe VZV infection after bone marrow transplantation. CASE REPORTS: The first patient was a 42-year old man who received an allogeneic bone marrow transplantation for chronic myelogenous leukemia. A severe graft-versus-host reaction occurred. Three months after discontinuing VZV prophylaxis, VZV transverse myelitis was diagnosed, leading to death despite prompt treatment with acyclovir. The second patient was a 42-year-old woman treated with autologous bone marrow transplantation for lymphoma. She developed acute viral pancreatitis one month after discontinuing VZV prophylaxis. Recovery was achieved with intravenous treatment. DISCUSSION: These two cases illustrate the potential gravity of VZV infection after bone marrow transplantation. These observations point to the need for revisiting the duration of VZV prophylaxis.

Assessment by flow cytometry of peripheral blood leukocyte enzymatic activities in HIV patients.

Leukocyte enzymatic activities are important in non-specific protection against bacterial infections, but traditional methods for the detection of intracellular enzymatic activities rely on cumbersome and complex assays. The development of specific substrates, which become fluorescent upon degradation of the biomolecule after its passive entry into intact cells, permits a simplified evaluation of leukocyte enzymatic activities. We have used this method to assess intracellular elastase, collagenase and cathepsin D activities of peripheral blood leukocytes using flow cytometry in a series of HIV patients and healthy controls. Monocytes displayed the highest enzymatic activities for the three proteases tested. In HIV-infected patients, the collagenase and cathepsin D activities of monocytes were significantly lower, whereas the elastase and cathepsin D activities of polymorphonuclear cells were elevated. Slightly higher elastase activity was detected in the lymphocytes of patients. This study demonstrates the feasibility of this new method for the study of intracytoplasmic enzymatic activities. Significant variations were observed in the peripheral blood of HIV-infected patients and different patterns were especially evident in monocytes and polymorphonuclear cells.

Tolerability of postexposure prophylaxis with zidovudine, lamivudine, and nelfinavir for human immunodeficiency virus infection.

Tolerability of the combination of zidovudine, lamivudine, and nelfinavir used as postexposure prophylaxis (PEP) for HIV infection was prospectively evaluated among 185 patients at 11 hospitals in eastern France. After exclusion of the 106 persons who discontinued PEP either because the source patient subsequently tested HIV seronegative or because the injury was reassessed as resulting in a low risk for transmission of HIV, 67 (85%) of the patients who received such PEP experienced adverse effects, which led to withdrawal of nelfinavir in 28 (35%) of these patients.

[Respiratory manifestations of hemorrhagic fever with renal syndrome. Retrospective study of 129 cases in Champagne-Ardenne and Lorraine]. / Manifestations respiratoires de la fièvre hémorragique avec syndrome rénal. Etude rétrospective de 129 cas en Champagne-Ardenne et Lorraine.

OBJECTIVES: The contradiction between airborne transmission of Puumala virus and the low rate of airway manifestations reported in hemorrhagic fever with renal syndrome (HFRS) caused by this virus led us to conduct this study to check whether the incidence of respiratory manifestations may have been underestimated. PATIENTS AND METHODS: We retrospectively reviewed 129 consecutive cases of HFRS diagnosed between 1983 and 1995 in the eastern France. RESULTS: Clinical manifestations of airway involvement and chest X-ray abnormalities were observed in 30% and 50% of the patients respectively. Analysing the radiological anomalies by serum creatinine level showed that in two-thirds of the cases (33% of all the HFRS cases) they were concomitant with acute renal failure and probably related to pulmonary edema, and that in one-third (17% of the HFRS cases) they were compatible with pneumonia. These cases of pneumonia could correspond to specific manifestations of the hantavirus Puumala at the site of penetration. CONCLUSION: Although minimally expressive, respiratory manifestations were found to be more frequent than expected in hemorrhagic fever with renal syndrome. Incidence may have been formerly underestimated.

Prospective validation of a diagnosis model as an aid to therapeutic decision-making in acute meningitis.

The aim of this study was to validate a diagnosis model that provides pABM, the probability of bacterial versus viral meningitis, based on four parameters collected at the time of first lumbar tap: cerebrospinal fluid protein level, cerebrospinal fluid polymorphonuclear cell count, blood glucose level, and leucocyte count. The model was evaluated prospectively as an aid to therapeutic decision-making in 109 consecutive patients with acute meningitis and negative cerebrospinal fluid Gram stain. In each case pABM was computed before a therapeutic decision and three diagnoses were established successively: (i) clinical evaluation, i.e. before pABM computation (bacterial meningitis, viral meningitis, or meningitis of undetermined origin); (ii) computation of pABM (viral meningitis if pABM< 0.1, bacterial meningitis otherwise); and (iii) determination of definitive diagnosis (bacterial meningitis: positive cerebrospinal fluid culture; viral meningitis: negative cerebrospinal fluid culture, no other aetiology and no treatment; meningitis of undetermined origin: cases fitting neither of the first two diagnoses). The computed diagnosis was viral meningitis in 78 of the 80 cases diagnosed definitively as viral meningitis, and bacterial meningitis in four of the five cases diagnosed definitively as bacterial meningitis. Negative and positive predictive values and accuracy of the model were 98.7%, 66.7%, and 96.5%, respectively. The clinical diagnosis was undetermined in 22 cases, 15 of which were diagnosed definitively as viral cases; in all of these 15 cases, the computed diagnosis was viral meningitis, leading the physician to refrain from starting antibiotics in all of them. The results confirm that the model evaluated is reliable and aids in the identification of patients in whom antibiotics can be safely avoided.

[Disseminated infestation of Enterocytozooon bieneusi a an HIV-infected patient]. / Infestation disséminée à Enterocytozoon bieneusi chez un patient infecté par le VIH.

An HIV-positive patient developed disseminated Enterocytozoon bieneusi infection. The parasite was identified in stool, duodenal biopsy, nasal discharge, and sputum specimens using transmission electron microscopy. Albendazole therapy failed to improve the symptoms or eradicate the parasite. The patient survived for nine months after the diagnosis of E. bieneusi infection.

[Seroprevalence of Central European tick-borne encephalitis in the Lorraine region]. / Séroprévalence de l'encéphalite à tiques d'Europe centrale en Lorraine.

BACKGROUND: Central European encephalitis, caused by the tick-borne encephalitis virus (TBEV), is exceptional in France. Most cases have been described in Alsace. As 2 cases of tick-borne encephalitis were diagnosed in the Nancy region, a seroepidemiological survey was conducted in the Lorraine region (Meurthe & Moselle, Moselle, Vosges, Meuse) in 1996. METHODS: The survey was proposed to approximately 1,000 persons attending preventive medicine clinics. The subjects were asked to fill out a self-administered questionnaire on factors related to tick bite exposure and underwent TBEV serology tests. RESULTS: 1,777 subjects participated in the survey. Half of them lived in rural areas, 91% had occasional or regular contact with the forest environment and 21% had experienced tick bites. TBEV serology (IgG) was positive in 19 subjects (1.6%; 95% CI: 0.9%-2.3%); 9 sera were positive on Western blot (0.76). No IgM positive serum was found. Seroprevalence was higher in subjects with a past history of tick bites compared with the others (2.9% vs 1.3%, p = 0.074). CONCLUSION: The low seroprevalence of TBEV in this survey is not in favor of widespread tick-bite encephalitis virus in the Lorraine general population.

Comparison of long term outcome in patients with or without aortic ring abscess treated surgically for aortic valve infective endocarditis.

OBJECTIVE: To assess the long term prognostic significance of aortic valve ring abscess in patients with aortic endocarditis. PATIENTS: A consecutive series of 75 patients who had surgery for aortic infective endocarditis between 1981 and 1989; 35 had aortic ring abscesses (group 1) and 40 did not (group 2). Mean age did not differ between the two groups. Prosthetic valve endocarditis was present in 17% of group 1 and 5% of group 2. Pneumococcal or beta haemolytic streptococcal endocarditis was more common in patients with native valve endocarditis who had aortic ring abscesses (20% v 5%). DESIGN: Cohort analysis. RESULTS: In-hospital mortality (11.4% v 7.5%) and 10 year survival (56% v 66%) were not significantly different between groups 1 and 2. In patients with native valve endocarditis, 10 year survival was 62% and 66%, respectively for patients with or without ring abscess, and 10 year reintervention-free survival was 38% v 58% (p = 0.11). In these patients, the presence of an intercurrent illness, severe congestive heart failure before surgery, and use of valved conduits for surgical treatment were predictors of poorer long term survival. At follow up residual aortic regurgitation was documented in 72% of patients in group 1 and 26% in group 2 (p < 0.01). CONCLUSIONS: Aortic valve ring abscess is not an independent marker of poor long term outcome in patients with infective endocarditis. However, as residual aortic regurgitation appears frequent at follow up, specific surgical techniques should be considered in patients with paravalvar abscesses.

Enterocytozoon bieneusi multiorgan microsporidiosis in a HIV-infected patient.

Multiorgan microsporidiosis due to Enterocytozoon bieneusi was diagnosed in an HIV-infected patient. The parasite was found and identified as E. bieneusi by transmission electron microscopy in stools, duodenal biopsy, nasal discharge and sputum. No clinical improvement or parasite eradication was obtained after albendazole therapy, but the patient remained alive 9 months after diagnosis.

Genital mycoplasmas in patients with acquired immunodeficiency syndrome.

To determine whether Mycoplasma fermentans. Mycoplasma genitalium and Mycoplasma penetrans were present in the genitourinary tract of HIV infected patients in Nancy, France, we have used culture and polymerase chain reactions on urine from 54 HIV-infected patients. Both techniques failed to reveal these bacteria. This renders their presence very unlikely in our population.