[Inquiry into the incidence of nosocomial infections and evaluation of the transmission of methicillin-resistant Staphylococcus aureus in an orthopedic surgical unit]. / Enquête d'incidence des infections nosocomiales et évaluation du portage de Staphylococcus aureus résistant à la méticilline dans un service de chirurgie orthopédique.

Nosocomial infections are an important cause of morbidity and mortality. Methicillin resistant Staphylococcus aureus (MRSA) is often the severe causal agent in this kind of infections. In order to evaluate risk factors for nosocomial infections and nasal MRSA carriage, an incidence study was carried out on patients hospitalized in an orthopaedic surgery department in Boucicaut Hospital (Paris). This study was carried out over a five month period. Data of all the patients who stayed more than two days in the unit were collected in medical and nursing records. Nasal swab specimens were taken at the admission of each patient included in order to screen nasal MRSA carriers. Statistical analysis were performed using Epi Info software version 6.0. A total of 451 patients were included in the study. Nosocomial infections incidence rate was 11.5%. Risk factor significantly associated with nosocomial infection was high wound containation classes III and IV (Altemeier). Incidence rate of MRSA carriage was 3.1%. A previous hospitalization in a general hospital 6 months before an admission at Boucicaut Hospital was the only risk factor identified. According to this, these patients, when they are admitted, are proposed to be preventely isolated awaiting their microbiological results.

Increased interferon-gamma (IFN-gamma) levels produced in vitro by alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon.

The aim of the present study was to analyse the in vitro proliferation and cytokine production by alloantigen-stimulated peripheral blood mononuclear cells (PBMC) obtained from patients affected by systemic sclerosis (SSc) and patients with Raynaud's phenomenon (RP). In SSc patients the proliferation of PBMC stimulated in vitro with alloantigens was significantly increased compared with healthy subjects, while no differences were observed for RP patients. Lymphocytes from SSc patients also produced larger amounts of IFN-gamma compared with healthy controls. However, patients with clinically active disease had lower IFN-gamma levels than those found in clinically stable patients. Patients affected by RP showed significantly higher levels of IFN-gamma than healthy subjects. Analysis at the clonal level of the lymphocyte subsets involved in alloantigen stimulation in one patient affected by active SSc, and one subject with RP confirmed the results obtained using PBMC. In particular, in the RP patient but not in the SSc patient, we observed a population of CD4+ T cells which proliferated to alloantigens in vitro and produced high levels of IFN-gamma. We suggest that T lymphocytes producing high levels of IFN-gamma might play a protective role in RP patients and in established scleroderma.

Endothelial tissue factor induction by T lymphocytes in systemic sclerosis.

We evaluated the ability of circulating T lymphocytes obtained from patients with systemic sclerosis (SSc) to induce the expression of tissue factor (TF) by human umbilical vein endothelial cells (HUVECs), and compared the results with those obtained from healthy controls. Nine patients with SSc and 10 sex- and age-matched healthy subjects were studied. Peripheral T lymphocytes obtained from SSc patients induced TF activity from HUVECs in a dose-dependent manner. A significant induction of endothelial TF was observed when 2 x 10(6) lymphocytes per well (TF values, mean+/-SD: 0.34+0.21U/microg of cell protein vs 0.04+/-0.03; n = 9, p = 0.001) or 1 x 10(6) lymphocytes per well (0.13+/-0.06 vs 0.04+/-0.04; n = 8, p<0.001) were added to HUVEC cultures. Lower concentrations of T lymphocytes were ineffective. Similar results were obtained with control lymphocytes. There were no differences in endothelial TF induction between patients and controls at any lymphocyte concentration tested. Within the SSc group, there were no correlations between TF activity and clinical features or disease duration.

Efficacy and safety of trazodone versus clorazepate in the treatment of HIV-positive subjects with adjustment disorders: a pilot study.

The efficacy of trazodone and clorazepate to relieve anxiety and depressive symptoms in 21 HIV-positive subjects with adjustment disorders was determined in a 28-day single-centre, randomized, double-blind study. Subjects were evaluated using the Hospital Anxiety and Depression Scale, the Revised Symptom Checklist, the European Organization for Research and the Treatment of Cancer Quality of Life Questionnaire, and a binary criterion based on the Clinical Global Impression. The incidence of successful treatment was 80% for trazodone compared with 64% for clorazepate; the sample number was too small to establish a significant difference. Bayesian analysis revealed the probability of making a wrong decision in prescribing trazodone rather than clorazepate reduced from 35% to 18% in this small sample. Clinical evaluations using the different scales suggest some benefit from trazodone, although this was not significant. Safety of both treatments was similar. Trazodone is devoid of the risk of abuse and dependence, and may be a valuable alternative to benzodiazepines for the treatment of HIV-related adjustment disorders.

High frequency of T-cell lines responsive to immunodominant epitopes of thyrotropin receptor in healthy subjects.

In this study we analyzed the proliferative response to the extracellular domain of thyrotropin receptor (TSHR-ECD) of T-cell lines raised from healthy subjects. We found high frequencies of cell lines reactive to TSHR-ECD, ranging from 12% to 37%. The response of the cell lines to a set of overlapping peptides of TSHR-ECD showed that the most recognized epitopes by T lymphocytes are on the C-terminal portion. In particular, the regions of residues 360-396 and 258-277 are immunodominant in T-lymphocyte reactivity. A group of cell lines specific for the peptides of TSHR-ECD lost the response to the peptides during time in culture. However, these lines were still responsive to TSHR extracellular domain. The cloning of one of these lines showed three types of T-cell clones: (1) CD4+ clones (n = 4) highly responsive to the TSHR-ECD; (2) CD4+ clones (n = 4) low responsive to TSHR-ECD; (3) CD8+ clones (n = 9) not responsive to TSHR-ECD. The first group of clones was stable during time in culture, while the second group was characterized by the loss of the specific response to TSHR-ECD after some weeks from the first analysis. The observation of a spontaneous anergy in the second group of CD4+ clones suggests that mechanisms of control of the lymphocyte response to TSHR-ECD could be activated in vitro.

Anti-thyroid antibodies in Italian scleroderma patients: association of anti-thyroid peroxidase (anti-TPO) antibodies with HLA-DR15.

OBJECTIVE: To evaluate the frequency of anti-thyroid antibodies in a group of patients with scleroderma (SSc) and to analyze their genetic association with the HLA class II antigens. METHODS: Anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO) antibodies were measured by hemagglutination techniques. Thyroid function was evaluated by determining the levels of FT3, FT4 and TSH. HLA-DR typing was carried out using a standard complement-dependent microlymphocytotoxicity test. RESULTS: The proportions of patients with anti-TG and anti-TPO antibodies were 12% (10/85) and 19% (16/85) respectively. Two patients with anti-thyroid antibodies had overt hypothyroidism and shared the HLA-DR3 allele. The SSc subjects with anti-TPO antibodies showed a higher frequency of the HLA-DR15 allele than the patients without these antibodies. CONCLUSION: A considerable number of patients with scleroderma have antibodies to thyroid antigens without exhibiting any alterations of their thyroid function. HLA-DR15 is an immunogenic marker for the formation of antibodies against microsomal thyroid peroxidase.

Cytokine production in scleroderma patients: effects of therapy with either iloprost or nifedipine.

OBJECTIVE: To compare the long-term effects of intermittent infusion of iloprost with those of oral nifedipine on the in vitro production of cytokines in patients with systemic sclerosis (SSc), and to evaluate their relationship with the effects of the two treatments on clinical parameters. METHODS: The production of cytokines by alloactivated circulating mononucleated cells was assessed before and after one year of treatment in a subset of 31 patients enrolled in a 12-month randomized clinical trial. Nineteen patients were treated with a 5-day (8 hr per day), 2.0 ng/kg per minute infusion followed by a 1-day infusion every 6 weeks; 12 patients were treated with an oral slow-release formulation of nifedipine, 20 mg twice daily. Quantitative determinations of interleukin-1 beta (IL1-beta) and interleukin-6 (IL6) in the culture supernatants were performed with a commercial ELISA; the levels of tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were measured by specific radioimmunometric assays. RESULTS: The production of IL1-beta was significantly lower in the iloprost group than in the nifedipine group. Both the cutaneous fibrosis and the capillaroscopic patterns were better in patients treated with iloprost than in patients treated with nifedipine. There was a significant positive covariance between IL1-beta changes and the changes in both the skin score and the capillaroscopic score. CONCLUSION: There are several mechanisms by which iloprost could exert its clinical efficacy. Vasodilatation and inhibition of platelet aggregation are certainly important, but they are transient. We suggest that the long-lasting modulation of the cytokine network observed in the present study could be another potential mechanism responsible for the persistent efficacy of iloprost despite its intermittent administration.

Differential effects of cyclo-oxygenase pathway metabolites on cytokine production by T lymphocytes.

Cyclo-oxygenase pathway metabolites released in the microenvironment by activated platelets and endothelial cells are potential local modulators of the immune response. In the present study, we have investigated the modulatory role of PGE2, iloprost (prostacyclin analogue), U-46619 (thromboxane analogue) on the release of IL-2, IFN-gamma, TNF-alpha and IL-6 by T lymphocytes. Our results show that PGE2 and prostacyclin differ in the regulation of cytokine production. PGE2 inhibited the release of IL-2 and IFN-gamma, while iloprost did not affect their production. The addition of PGE2 or iloprost greatly decreased the amount of TNF-alpha measured in the supernatants, although the rates of inhibition differed according to the kind of stimulation. Unlike that of PGE2, inhibition by iloprost was stronger in alloactivated cultures than in PHA-stimulated ones. In vitro IL-6 production was stimulated by PGE2 in alloactivated cultures and by iloprost, whatever the stimulus. These results are probably due to other cellular subsets contaminating the T-lymphocyte preparations. After complete removal of monocytes from cell cultures, there were inhibitory effects of lloprost and PGE2 on IL-6 released in the supernatants. We did not observe any significant effect of thromboxane analogue on the production of either cytokine.

Secretion of cytokines upon allogeneic stimulation: effect of aging.

The aim of the present study was to investigate the in vitro mitotic response and cytokine production after allogeneic stimulation of peripheral blood mononuclear cells (PBMC) from healthy elderly subjects. Interleukin-1 (IL-1), interleukin-2 (IL-2), gamma-Interferon (gamma-IFN), and Tumor Necrosis Factor alpha (TNF-alpha) were detected in the supernatants of mixed lymphocyte cultures (MLC). The in vitro proliferative response was significantly reduced in the elderly subjects. The amount of IL-2 detected in the supernatant from cultures of cells from elderly donors was higher than for young controls, as were the production of cytokines predominantly secreted by the macrophage population (IL-1 and TNF-alpha). There was no difference in the production of gamma-IFN by cells of elderly and young subjects.

[Relation between age, sex and various metabolic parameters: blood uric acid (4776 specimens), blood sugar (7211 specimens), blood cholesterol (5600 specimens) and blood triglycerides (4438 specimens)]. / Relazione tra età, sesso e alcuni parametri metabolici: uricemia 4776 dati, glicemia 7211 dati, colesterolemia 5600 dati, trigliceridemia 4438 dati.

The connection between age, sex and some laboratory parameters (blood uric acid, glucose, cholesterol and triglycerides) has been studied on a very wide whole (22025 exams). An important datum which has appeared is that the increase of age is connected with an increase of the values of the parameters studied, and that the sex conditions differences which proved statistically significant.