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.

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.

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.

LFA1 expression in HIV infection.

The expression of the adhesion molecule LFA1 was investigated in mononuclear cells from 200 samples of peripheral blood obtained from asymptomatic HIV-infected individuals and AIDS patients. The numbers and percentages of LFAI-positive cells were established by indirect immunofluorescence. A significant decrease in the number of labelled cells was observed (mean percentage 68.9) while 100% of the cells were positive in controls. These data suggest that LFA1-mediated cell-cell cooperation might be impaired in HIV infection, adding to the immune deficiency related to the disappearance of CD4+ cells.

Extracerebral toxoplasmosis in patients infected with HIV. A French National Survey.

A French nationwide survey of extracerebral toxoplasmosis (ECT) in HIV-infected patients was performed between January 1990 and September 1992. All French hospitals were surveyed, and all but a few responded. Data collected included epidemiologic, clinical, and biologic features; therapy; and outcome. During the 33-month survey, 199 cases were collected. The prevalence of ECT in patients with AIDS can be estimated at 1.5%-2%. Age, sex, and HIV risk factors were similar to those of the general AIDS population in France. Extracerebral toxoplasmosis appeared mainly in HIV-infected patients with advanced immunosuppression: the mean CD4+ lymphocyte count was 57/mm3(+/- 99). The localizations observed were: eyes (50% of patients); lung (26%); disseminated (at least 2 extracerebral visceral localizations) (11.5%); peripheral blood (acute febrile syndrome with isolated positive parasitemia) (3%); heart (3%); bone marrow (3%); bladder (1%); and isolated cases of rhinopharynx, skin, liver, lymph nodes, conus medullaris, and pericardium. In this survey, muscular and pancreatic localizations were always associated with other extracerebral localizations. A cerebral localization was diagnosed in 41% of cases. Serologic data provided little information. Ocular fundus examination, bronchoalveolar lavage, tissue biopsy, and search for parasitemia were the main diagnostic procedures. Treatment was the same as for cerebral toxoplasmosis. A clinical response was observed in 64% of cases; 19% relapsed. Death occurred in 106 (53%) cases and was related to ECT in 34% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. LFPMI Study Group. Ligue Française de Prévention des Maladies Infectieuses.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

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.

Relapsing congestive cardiomyopathy in Wegener's granulomatosis.

Congestive cardiomyopathy is a highly unusual complication of Wegener's granulomatosis. In this report, we describe a 37-year-old man with histologically proven Wegener's granulomatosis who had two episodes of severe hypokinetic cardiomyopathy that responded well to cyclophosphamide. The theory that cardiomyopathy might be related to cardiac involvement in Wegener's granulomatosis and the beneficial effect of cyclophosphamide in this condition are discussed.

Schnitzler's syndrome: two case reports and review of the literature.

Schnitzler's syndrome is a combination of chronic urticaria, fever of unknown origin, disabling bone pain, hyperostosis, increased erythrocyte sedimentation rate, and macroglobulinemia. Since it was first described in 1974, only 26 cases have been published in the literature. In this report, we describe two additional cases and review the clinical features and pathogenesis of this uncommon syndrome.

Tuberculosis in Lorraine, France: study of prognostic factors.

AIM: To identify factors predicting short-term mortality in patients with tuberculosis in the Lorraine region of France. METHOD: Retrospective survey in nine voluntarily participating hospitals between January 1990 and December 1994. RESULTS: In total 351 files were analyzed. The average age of patients was 49 +/- 19 years; 77% were of French origin, 60% were male; 35% were in paid employment at the time of the diagnosis, 42% were unemployed and 23% were retired. Twenty-three patients were infected by the human immunodeficiency virus (HIV), and 34 patients had a prior history of tuberculosis; 79% of all cases were exclusively pulmonary, 14% were exclusively extra-pulmonary (more frequent in women) and 7% were mixed. Extra-pulmonary sites of involvement were more frequent in HIV-infected patients. Chest X-ray was suggestive of tuberculosis in 158 patients with pulmonary involvement, and non-suggestive in 145 (more frequently in HIV-infected patients). In univariate analysis, HIV co-infection, increasing age and unemployment were linked to death during treatment. In multivariate analysis (logistic regression), HIV co-infection, old age, unemployment, pulmonary involvement and French origin were significantly linked to the risk of death during treatment.

Clinical and bacteriological characteristics of infective endocarditis in the elderly.

OBJECTIVE: To determine the clinical and bacteriological features of infective endocarditis in the elderly. DESIGN: Prospective case series. SETTING: A university hospital that is both a referral and a primary care centre. PATIENTS: 114 consecutive patients treated for infective endocarditis from November 1990 to December 1993: 25 were > 70 years of age (group 1) and 89 were < 70 years old (group 2). RESULTS: Location of infective endocarditis, clinical signs, and symptoms were similar in the two groups, except for a lower occurrence of embolic episodes in the elderly (group 1:8%, group 2: 28%; P < 0.04). A higher rate of infective endocarditis on intracardiac prosthetic devices was noted in group 1 (group 1: 52%, group 2: 25%; P < 0.05). The distribution of causative micro-organisms showed a higher proportion of bacteria from the gastrointestinal tract in the elderly (group D streptococci and enterococci: 48% in group 1 v 20% in group 2) and the presumed portal of entry was more often digestive (group 1: 50%, group 2: 17%; P = 0.01). Elderly patients were less often operated on (group 1: 24%, group 2: 43%; P = 0.07) and their mortality rate was higher (group 1: 28%, group 2: 13%; P = 0.08). CONCLUSIONS: Infective endocarditis in patients over 70 often occurs in those with intracardiac prosthetic devices and is more often due to bacteria from the gastrointestinal tract. Its prognosis appears to be worse than in younger subjects.

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.

Relationship of trace element, immunological markers, and HIV1 infection progression.

Trace elements (selenium, zinc, copper), beta 2 microglobulin levels, CD4, and CD8 cell counts have been determined in 80 HIV1 seropositive patients. The study group consisted of 19 females and 61 males with age mean of 35 +/- 10 yr, at stage IV of infection (CDC--Atlanta classification) and treated by AZT. No severe renal or liver diseases or hypoalbuminemia were observed in this group. Se values were significantly lower than in normal adults, 48.3 +/- 17 micrograms/L vs 71 +/- 12 micrograms/L; Zn was moderately diminished, 1 +/- 0.2 mg/L vs 1.2 +/- 0.2 mg/L, whereas copper values were in the normal range, 1.2 +/- 0.3 mg/L vs 1.1 +/- 0.5 mg/L. Se or Zn deficiency was found in 60 and 30 subjects, respectively. Blood Se and Zn decreases were associated in 23 patients. Moreover, all patients showed higher beta 2 microglobulin values than the upper normal limit of 2.4 mg/L. Negative correlations were found between Zn and beta 2 microglobulin (p < 0.005) and between Se and beta 2 microglobulin (p < 0.05). Moreover, there was a positive correlation between Se and Zn values (p < 0.05). Nineteen subjects died 1 yr later (group I), and 61 remained alive (group II). With respect to the clinical evolution, a significant difference between both groups was found in Se and beta 2 microglobulin levels as well as in CD4 cell counts. The correlations previously observed persisted in group II, whereas no correlation was noted in group I. In addition, the patients of group one had significantly lower Se values, which were below 30 micrograms/L in 10 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

[Comparative outcome of aortic valve endocarditis with or without annular abscess]. / Profil évolutif comparé des endocardites aortiques avec ou sans abcès de l'anneau.

Annular abscess is a not uncommon but serious complication of aortic valve endocarditis. The aim of this retrospective study was to evaluate the prognosis of aortic valve endocarditis with and without annular abscess. Between January 1981 and 1989, 122 consecutive cases of aortic endocarditis fulfilling the diagnostic criteria of Duke University were admitted to hospital. Group I included 40 cases with aortic ring abscess confirmed at surgery, in 35 patients; group II comprised 43 cases of operated aortic valve endocarditis without annular abscess in 41 patients and group III comprised 38 cases of aortic valve endocarditis treated medically without echocardiographic or angiographic signs of annular abscess in 36 patients. The patients in group III were significantly older than those in group I (57 +/- 14 years vs 44 +/- 17 years; p < 0.001). From the clinical point of view, endocarditis of prosthetic valves was slightly more common, but without reaching statistical significance, in group I, but the abscess was associated with more severe cardiac failure. Systemic embolism, atrioventricular block and pericardial effusion were equally common in the three groups. On the other hand, endocarditis with annular abscess was more often the result of infection with streptococci A, B, C or pneumoniae, than forms without abscess (22.5% vs 5% and 3% respectively in the 3 groups; p < 0.05). Of the patients treated surgically, destructive lesions of the valves were more common in cases of abscess (57.5% vs 35%; p < 0.05): the hospital mortality was higher in cases of abscess (17.5% vs 7%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Anal and perianal lesions in symptomatic HIV infections. Prospective study of a series of 190 patients]. / Lésions anales et péri-anales au cours des infections symptomatiques par le VIH. Etude prospective d'une série de 190 patients.

The aim of this study was to determine the prevalence and type of symptomatic anal and perianal diseases in patients belonging to group IV of the Centers for Disease Control classification of infections with human immuno-deficiency virus. Among the 190 prospectively included patients, 31 (16.3 percent) (30 men, 29 homosexuals or bisexuals; 1 woman) had anal symptoms and were referred for proctological examination. Thirty-five "specific" diagnoses were reached in 25 (13.2 percent) patients: 21 ulcerations, 7 condyloma acuminata, 6 perianal sepsis and 1 non-Hodgkin malignant lymphoma. The causes of ulcerations were 16 herpes, one syphilitic chancre and one fissure-in-ano. Three ulcerations remained unexplained despite bacteriological, viral, and histological investigations. Eight patients underwent 10 surgical procedures without significantly delayed wound healing.

[Molecular typing by pulsed field gel electrophoresis of Enterobacter cloacae strains isolated from osteoarticular infections at the Nancy University Hospital 1990-1994]. / Typage moléculaire par électrophorèse en champ pulsé des souches d'Enterobacter cloacae isolées d'infections ostéo-articulaires au CHU de Nancy de 1990 à 1994.

Enterobacteriaceae represent more than 11% of bacteria involved in osteoarticular infections in adult and, among them, Enterobacter cloacae is found in 12% of the cases. The increased evolution of the antibiotic resistance rate of this species is worrying. However, all isolates responsible for this type of infection at the University Hospital of Nancy from 1990 to 1994 (24 strains isolated from 22 patients presented an identical antibiotype with especially a natural resistance phenotype to beta-lactam antibiotics except one cephalosporinase-over-producing strain. The DNA of these strains was studied by pulse-field gel electrophoresis after digestion by the restriction enzyme XbuI. The great genomic diversity obtained showed that the stability of the antibiotic susceptibility during the period studied was not due to the existence of unique clone but to that of multiple clones. The analysis of the restriction profiles has permitted to achieve a better differenciation of the strains than biotyping and antibiotyping, which confirms the high discrimination power of this genotypic method.

[Free radicals and HIV infection]. / Radicaux libres et infection par le VIH.

In HIV infected patients, the increase of the concentration of free radicals is related to: a depletion of protective system (glutathione peroxidase, superoxide dismutase, vitamin E, selenium ...), and an increased production of free radicals (superoxide anion, hydrogen peroxide, hydroxil radical) consecutive to the activation of lymphocytes and phagocyting cells, the chronic inflammation, the increased polyinsatured fatty acids concentration and lipoperoxidation, and direct or indirect effect of several pathologic agents including Mycoplasma sp. This free radical excess could impair cell membranes and generate apoptosis, the main cause of lymphocytes CD4+ depletion. After a brief review of the free radicals synthesis pathway, their potential deleterious effects and the protective systems, the role of free radicals in the pathogenesis of HIV infection are discussed in regard to data reported in the literature.