Bilateral Non-arteritic Anterior Ischaemic Optic Neuropathy as the Presentation of Systemic Amyloidosis.

A 75-year-old hypertensive female with stable idiopathic intermediate uveitis presented with bilateral sequential optic neuropathy with optic disc swelling. The optic neuropathy in the first affected eye (right) was thought to be due to non-arteritic anterior ischaemic optic neuropathy (NAION). Asymptomatic left optic disc swelling was found at routine review 2 months later, and a diagnosis of giant cell arteritis (GCA) was sought. Temporal artery duplex ultrasound showed the "halo sign," but a subsequent temporal artery biopsy showed light-chain (AL) amyloidosis with no signs of giant cell arteritis. In this case, bilateral sequential ischaemic optic neuropathy mimicking non-arteritic anterior ischaemic optic neuropathy was the presenting sign of systemic amyloidosis involving the temporal arteries.

Synovial CD4+ T-cell-derived GM-CSF supports the differentiation of an inflammatory dendritic cell population in rheumatoid arthritis.

OBJECTIVE: A population of synovial inflammatory dendritic cells (infDCs) has recently been identified in rheumatoid arthritis (RA) and is thought to be monocyte-derived. Here, we investigated the role and source of granulocyte macrophage-colony-stimulating factor (GM-CSF) in the differentiation of synovial infDC in RA. METHODS: Production of GM-CSF by peripheral blood (PB) and synovial fluid (SF) CD4+ T cells was assessed by ELISA and flow cytometry. In vitro CD4+ T-cell polarisation experiments were performed with T-cell activating CD2/CD3/CD28-coated beads in the absence or presence of pro-Th1 or pro-Th17 cytokines. CD1c+ DC and CD16+ macrophage subsets were flow-sorted and analysed morphologically and functionally (T-cell stimulatory/polarising capacity). RESULTS: RA-SF CD4+ T cells produced abundant GM-CSF upon stimulation and significantly more than RA-SF mononuclear cells depleted of CD4+ T cells. GM-CSF-producing T cells were significantly increased in RA-SF compared with non-RA inflammatory arthritis SF, active RA PB and healthy donor PB. GM-CSF-producing CD4+ T cells were expanded by Th1-promoting but not Th17-promoting conditions. Following coculture with RA-SF CD4+ T cells, but not healthy donor PB CD4+ T cells, a subpopulation of monocytes differentiated into CD1c+ infDC; a process dependent on GM-CSF. These infDC displayed potent alloproliferative capacity and enhanced GM-CSF, interleukin-17 and interferon-γ production by CD4+ T cells. InfDC with an identical phenotype to in vitro generated cells were significantly enriched in RA-SF compared with non-RA-SF/tissue/PB. CONCLUSIONS: We demonstrate a therapeutically tractable feedback loop of GM-CSF secreted by RA synovial CD4+ T cells promoting the differentiation of infDC with potent capacity to induce GM-CSF-producing CD4+ T cells.

Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction.

Mesenchymal stromal cells (MSCs) are cardioprotective in acute myocardial infarction (AMI). Besides, we have shown that intramyocardial injection of plasmid-VEGF(165) (pVEGF) in ovine AMI reduces infarct size and improves left ventricular (LV) function. We thus hypothesized that MSCs overexpressing VEGF(165) (MSCs-pVEGF) would afford greater cardioprotection than non-modified MSCs or pVEGF alone. Sheep underwent an anteroapical AMI and, 1 week later, received intramyocardial MSCs-pVEGF in the infarct border. One month post treatment, infarct size (magnetic resonance) decreased by 31% vs pre-treatment. Of note, myocardial salvage occurred predominantly at the subendocardium, the myocardial region displaying the largest contribution to systolic performance. Consistently, LV ejection fraction recovered to almost its baseline value because of marked decrease in end-systolic volume. None of these effects were observed in sheep receiving non-transfected MSCs or pVEGF. Although myocardial retention of MSCs decreased steeply over time, the treatment induced significant capillary and arteriolar proliferation, which reduced subendocardial fibrosis. We conclude that in ovine AMI, allogeneic VEGF-overexpressing MSCs induce subendocardial myocardium salvage through microvascular proliferation, reducing infarct size and improving LV function more than non-transfected MSCs or the naked plasmid. Importantly, the use of a plasmid rather than a virus allows for repeated treatments, likely needed in ischemic heart disease.

First operation in SPIDER and the path to complete MITICA.

The requirements of ITER neutral beam injectors (1 MeV, 40 A negative deuterium ion current for 1 h) have never been simultaneously attained; therefore, a dedicated Neutral Beam Test Facility (NBTF) was set up at Consorzio RFX (Padova, Italy). The NBTF includes two experiments: SPIDER (Source for the Production of Ions of Deuterium Extracted from Rf plasma), the full-scale prototype of the source of ITER injectors, with a 100 keV accelerator, to investigate and optimize the properties of the ion source; and MITICA, the full-scale prototype of the entire injector, devoted to the issues related to the accelerator, including voltage holding at low gas pressure. The present paper gives an account of the status of the procurements, of the timeline, and of the voltage holding tests and experiments for MITICA. As for SPIDER, the first year of operation is described, regarding the solution of some issues connected with the radiofrequency power, the source operation, and the characterization of the first negative ion beam.

Thymic function in juvenile idiopathic arthritis.

OBJECTIVE: Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined. METHODS: Thymic function was measured in 70 children and young adults with JIA (age range 2.1-30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4(+) CD45RA(+)CD31(+) T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the alphaTREC/SigmabetaTREC ratio. Lastly, regulatory T cells (T(Reg)) of thymic origin (CD4(+)FOXP3(+)) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset. RESULTS: Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)(+) polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD. CONCLUSIONS: It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term "JIA" suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.

Determination of thymic function directly from peripheral blood: a validated modification to an established method.

The thymus contributes naïve, self MHC reactive, self tolerant T cells to the peripheral immune system throughout life, albeit with a log-linear decline with age. Quantification of thymic function is clinically relevant in the setting of lymphoablation, but a phenotypic marker distinguishing recent thymic emigrants from long lived naïve T cells remains elusive. T cell receptor excision circles (TREC) are present in thymocytes exiting the thymus and quantification of the most frequent of these, the deltarec-psiJalpha rearrangement has been widely used as a measure of recent thymic function. However, interpretation of results presented as TREC per cell has been criticised on the basis that extra-thymic cellular proliferation impacts on peripherally determined TREC numbers. TREC/ml is now considered to be more representative of thymic function than TREC/cell, especially where significant cellular proliferation occurs (e.g. during reconstitution following stem cell transplantation). Here we describe the validation of a novel variation to the established assay, directly quantifying TREC/ml from 300 microl whole blood. We show the assay to be reproducible, robust and stable longitudinally and we show equivalence of performance when compared with more standard assays. This assay particularly lends itself to the measurement of thymic function in children and where monitoring clinical variables is limited by tissue availability.

Multi-scale laboratory routine in the efficacy assessment of conservative products for natural stones.

The evaluation of conservative treatments' efficacy on natural building stones are usually based on standard recommendation routines finalized to evaluate compatibility and harmfulness of products in turn of the substrate. However, the visualization and the quantification of products inside pore structure of natural stones is not immediate through standard tests, so that imaging and advanced techniques are recently proposed in material conservation field to improve knowledge on penetration depth, modification of pore-air interface at different scale and monitor dynamic absorption processes. Moreover, natural stones are usually characterized by complex structure, which changes due to conservative treatments have to be inspected at different scale (from micrometer to nanometer). In this prospective, the assessment of laboratory practices able to integrate multiscale methods and give back a complete overview on interaction between new conservative formulates and natural stones is of high interest. In this paper, we propose a methodological routine for efficacy assessment of conservative products, incorporating classical and innovative nondestructive techniques. Validation of the workflow has been verified on a high porous natural stone treated with new hybrid formulates appropriately customized for conservation issues. •The study intends to add new insights on problems related to consolidation of high porous carbonate stone, application methods in consolidating natural stones and methods to evaluate efficacy of new products.•A multi-scale laboratory investigation procedure is proposed by integrating standard and innovative nondestructive methods. Merits and limits of each applied method are discussed during validation.•The possibility to incorporate standard routines and/or substitute destructive testing with non-destructive ones seem to be a valid alternative to evaluate efficiency and monitor behavior of stones treated with consolidating products.

A new deflection technique applied to an existing scheme of electrostatic accelerator for high energy neutral beam injection in fusion reactor devices.

A scheme of a neutral beam injector (NBI), based on electrostatic acceleration and magneto-static deflection of negative ions, is proposed and analyzed in terms of feasibility and performance. The scheme is based on the deflection of a high energy (2 MeV) and high current (some tens of amperes) negative ion beam by a large magnetic deflector placed between the Beam Source (BS) and the neutralizer. This scheme has the potential of solving two key issues, which at present limit the applicability of a NBI to a fusion reactor: the maximum achievable acceleration voltage and the direct exposure of the BS to the flux of neutrons and radiation coming from the fusion reactor. In order to solve these two issues, a magnetic deflector is proposed to screen the BS from direct exposure to radiation and neutrons so that the voltage insulation between the electrostatic accelerator and the grounded vessel can be enhanced by using compressed SF6 instead of vacuum so that the negative ions can be accelerated at energies higher than 1 MeV. By solving the beam transport with different magnetic deflector properties, an optimum scheme has been found which is shown to be effective to guarantee both the steering effect and the beam aiming.

Amino acid uptake in vivo by the mouse brain and by various regions of the rabbit brain after drug-induced convulsions.

The levels of the free amino acids of the mouse brain were studied after convulsions induced by Metrazol; a decrease of level of taurine and a significant increase of level of alanine, phenylalanine and isoleucine were found. The net uptake of L-histidine by the mouse brain in vivo was similar under normal conditions and after Metrazol-induced generalized convulsions; that of L-methionine was much higher after convulsions and there was no uptake of L-aspartic acid, either under physiological conditions or after convulsions. The net uptake of L-histidine by various regions of the rabbit brain in vivo after convulsions was significantly higher than control values in the cortical areas, while that of L-methionine was significantly higher in the subcortical ones; there was no uptake of L-aspartic acid by the rabbit brain in normal condition, whereas after convulsions a small entry seemed to occur in the subcortical areas. These results indicate that cerebral permeability processes of amino acids are somewhat altered during convulsive phenomena, as already described elsewhere for ions andproteins.

Antimicrobial activity of norfloxacin in enteric and urinary tract infections: combined effect of norfloxacin with aminoglycosides, tetracycline and chloramphenicol.

A comparative study of the in vitro activity of norfloxacin was performed versus that of aminoglycosides, pipemidic acid, tetracycline and chloramphenicol. These antibiotics are the most commonly used antimicrobial agents in the treatment of enteric and urinary tract infections. Results obtained with norfloxacin against Gram-negative isolates tested were very encouraging. MIC values for the Enterobacteriaceae were less than or equal to 0.47 mcg/ml, and for Pseudomonas and Acinetobacter less than or equal to 32.5 mcg/ml. The activity of norfloxacin against Pseudomonas was inferior to that of amikacin, but superior to that of gentamicin. In association with aminoglycosides, norfloxacin proved to be most useful in the treatment of urinary tract infections, while norfloxacin associated with tetracycline and chloramphenicol did not give satisfactory results in the treatment of enteric infections.

Multiple sclerosis and pregnancy.

Multiple sclerosis causes disability in young adults and, like most autoimmune diseases, affects women more commonly than men. The disease can therefore present at a time when many have, or are considering, starting a family. The effect of pregnancy on the outcome of multiple sclerosis is reviewed and the management of pregnant women who have multiple sclerosis is discussed.

[Minimal inhibitory and bactericidal concentrations of cefoperazone, cefotaxime, cefuroxime and cefalotin against 90 bacterial strains]. / Minime concentrazioni inibenti e battericide del cefoperazone, cefotaxime, cefuroxime e cefalotina nei confronti di 90 ceppi batterici.

In this work, the sensitivity in vitro of cefoxitin, cefuroxime, cefotaxime, cefoperazone and cephalothin have been examined. Test of sensitivity in vitro have been performed as by Kirby-Bauer method as by measurement of MIC and MBC. Then the regression lines have been determined. Cefotaxime and cefoperazone provided nearly complete coverage of all Enterobacteriaceae; 80% were inhibited at less than or equal to 2 mcg./ml. This value is far below therapeutically attainable serum concentrations. Cefotaxime has MIC lower than cefoperazone. It has a significant spectrum of activity against Pseudomonas aeruginosa, nonenterococcal Streptococcus sp, non Enterobacteriaceae Gram-negative bacilli. Only enterococci and Acinetobacter species were relatively resistant to cefoperazone and cefotaxime. The cephalothin and the cefoxitin included excellent antimicrobial coverage of the staphylococci and the anaerobic bacteria respectively.

Gastric antral vascular ectasia in systemic sclerosis: complete resolution with methylprednisolone and cyclophosphamide.

A case of severe, transfusion dependent anaemia in a 72 year old woman, which on endoscopy was found to be due to gastric antral vascular ectasia (GAVE), is reported. Repeated endoscopic sclerotherapy was ineffective. She subsequently developed Raynaud's phenomenon and on further investigation was found to have classical systemic sclerosis with lung involvement. Treatment with pulses of intravenous methylprednisolone and cyclophosphamide resulted in significant improvement in her pulmonary function tests and skin score. Coincidentally, her haemoglobin stabilised and further endoscopic examinations were normal. This is the first report of cyclophosphamide and methylprednisolone leading to complete and sustained resolution of GAVE in association with systemic sclerosis.

A reconciliation of continuous and tidal ventilation gas exchange models.

Continuous-ventilation mathematical gas exchange models are widely used since their analytical equations are amenable to physiological interpretation. They describe qualitatively the respiratory system's response to changing physiological conditions, but do not calculate accurate values for respiratory parameters when experimental tidal ventilation expired gas data are inserted into their analytical expressions. A simple mathematical expression is presented to reconcile continuous and tidal ventilation gas exchange models. Tidal ventilation experimental data can then be inserted into conventional continuous ventilation equations to produce more accurate measures of lung volume. This hypothesis is tested with controlled experimental tidal ventilation tracer gas data obtained from both wash-out and forced inspired sinusoid experiments, using a mechanical lung model with known volume; tidal volume, VT; and series 'airway' dead space VD. We show that the subtraction of 1/2 (VT + VD) from the lung volume calculated from the continuous ventilation theory can produce lung volume measurements which agree with the true lung volume to within +/-5%, for physiological lung volume values, for both wash-out and forced sinusoid techniques.

High-Resolution Infrared Spectrum of Vinyl Fluoride at 500 cm-1

The infrared spectrum of vinyl fluoride (CH2=CHF) has been investigated in the region 390-590 cm-1 at room temperature and at a resolution of 0.0016 cm-1 using a Fourier transform spectrometer. The rovibrational analysis of the spectral features allowed us to assign about 11 000 lines (J