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Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background Tetralogy of Fallot is the most common cyanotic congenital heart disease and requires right ventricular outflow tract (RVOT) replacement. RVOT substitutes are suboptimal, functionally deteriorating within a few years and necessitating a series of surgical reinterventions. An optimal prosthetic that mimics the structural and mechanical properties of native tissue is desirable. However, due to inadequate homo/autograft availability for neonates and infants, xenografts are commonly used in paediatric cardiac surgery. Current xenografts are limited by lack of growth, susceptibility to calcification, and limited remodelling capacity. Decellularisation to remove immunogenic antigens on the animal-derived tissue reduces the risk of graft rejection. Decellularisation conditions are critical: harsh treatment will disrupt extracellular matrix components vital for in vivo recellularisation; conversely, a too mild treatment may lead to incomplete cell removal and graft degeneration. Decellularisation of valved conduits poses a unique challenge as the valve structure differs significantly to that of the artery. The latter is thicker and stronger, requiring harsher detergents which could damage the valve. Purpose This research optimises an in vitro decellularisation protocol for simultaneous removal of porcine cells from the right ventricle (RV), pulmonary artery (PA), and pulmonary valve (PV). We ultimately plan to recellularise the cell-free RVOT scaffold with autologous mesenchymal stem cells via a tissue-engineering approach, endowing the xenograft with growth capacity and improved biocompatibility compared to existing products, thus overcoming the limitations of the currently used replacement grafts. Methods The integrated valved RVOT conduits were harvested from pigs and mounted in a temperature-controlled bioreactor chamber. Decellularisation solutions were circulated through the lumen and around the outside of the submerged conduit under constant flow, with extended sodium dodecyl sulfate and nuclease washes. Histological assessment of the RV, PA, and PV by Heamatoxylin and Eosin, for nuclei detection, and Elastin van Gieson’s staining, for elastin and collagen content, report on decellularisation success. Results Preliminary results demonstrate effective decellularisation of the RV, PA, and PV in both the valved conduit decellularised immediately after harvesting and following one freeze-thaw cycle. The ability to freeze RVOTs until needed would facilitate production of an accessible surgical product. Images reveal nuclei elimination in each tissue architecture whilst the extracellular matrix composition appears unchanged. Conclusions Concurrent multi-tissue decellularisation revealed promising structural results, however mechanical properties of the cell-free RVOT must be assessed to deem decellularisation successful. Further experiments are underway to evaluate the scaffold’s capacity to support mesenchymal stem cell repopulation.

Cell therapy represents a promising option for revascularization of ischemic tissues. However, injection of dispersed cells is not optimal to ensure precise homing into the recipient's vasculature. Implantation of cell-engineered scaffolds around the occluded artery may obviate these limitations. Here, we employed the synthetic polymer polycaprolactone for fabrication of 3D woodpile- or channel-shaped scaffolds by a computer-assisted writing system (pressure assisted micro-syringe square), followed by deposition of gelatin (GL) nanofibers by electro-spinning. Scaffolds were then cross-linked with natural (genipin, GP) or synthetic (3-glycidyloxy-propyl-trimethoxy-silane, GPTMS) agents to improve mechanical properties and durability in vivo. The composite scaffolds were next fixed by crown inserts in each well of a multi-well plate and seeded with adventitial progenitor cells (APCs, 3 cell lines in duplicate), which were isolated/expanded from human saphenous vein surgical leftovers. Cell density, alignment, proliferation and viability were assessed 1 week later. Data from in vitro assays showed channel-shaped/GPTMS-crosslinked scaffolds confer APCs with best alignment and survival/growth characteristics. Based on these results, channel-shaped/GPTMS-crosslinked scaffolds with or without APCs were implanted around the femoral artery of mice with unilateral limb ischemia. Perivascular implantation of scaffolds accelerated limb blood flow recovery, as assessed by laser Doppler or fluorescent microspheres, and increased arterial collaterals around the femoral artery and in limb muscles compared with non-implanted controls. Blood flow recovery and perivascular arteriogenesis were additionally incremented by APC-engineered scaffolds. In conclusion, perivascular application of human APC-engineered scaffolds may represent a novel option for targeted delivery of therapeutic cells in patients with critical limb ischemia.

Background: Cortisol binding globulin (CBG) is produced by liver cells and is inhibited by proinflammatory cytokines such as interleukin (IL) 6. CBG serum levels are typically low during prolonged inflammatory processes. Thus, observed changes of cortisol during anti-tumour necrosis factor (TNF) treatment may be related to changes of CBG in rheumatoid arthritis (RA). Objective: To investigate the course of CBG during anti-TNF treatment in RA. Methods: 13 patients with longstanding RA, without prior prednisolone treatment, were included in this longitudinal study with subcutaneous adalimumab. Results: Treatment with anti-TNF markedly decreased clinical markers of inflammation and serum IL6. Serum levels of cortisol, CBG, and the ratio of cortisol/CBG did not change markedly, whereas the ratio of serum CBG/IL6 increased (p = 0.004). In parallel, levels of adrenocorticotropic hormone decreased during the observation period. The ratio serum androstenedione/serum cortisol increased during the study (p = 0.036). Conclusions: During anti-TNF treatment relatively normal levels of CBG and a normal ratio of CBG/cortisol are found. Changes of cortisol in relation to IL6 during anti-TNF treatment, seen previously, may not be related to changes of CBG.

Cone penctrometer test (CPT) based Raman spectroscopy was used to identify separate phase tetrachloroethylene (PCE) and trichlorocthylene (TCE) contamination in the subsurface at two locations during field tests conducted at the U.S. Department of Energy's (DOE) Savannah River site. Clear characteristic Raman spectral peaks for PCE and TCE were observed at two sites and several depths during CPT deployment. Because of the uniqueness of a Raman spectrum for a given compound, these data are compelling evidence of the presence of the two compounds. The Raman spectral results correlated with high PCE and TCE concentrations in soil samples collected from the same subsurface zones, confirming that the method is a viable dense nonaqueous phase liquid (DNAPL) characterization technique. The Raman spectroscopic identification of PCE and TCE in these tests represents the first time that DNAPLs have been unequivocally located in the subsurface by an in situ technique. The detection limit of the Raman spectroscopy is related to the probability of contaminant droplets appearing on the optical window in the path of the probe light. Based on data from this fieldwork the Raman technique may require a threshold quantity of DNAPL to provide an adequate optical cross section for spectroscopic response. The low aqueous solubility of PCE and TCE and relatively weak optical intensity of the Raman signal precludes the detection of aqueous phase contaminants by this method, making it selective for DNAPL contaminants only.

A portable fiber-optic Raman system comprising a diode laser, echelle spectrograph, charge-coupled device (CCD) detector, and filtered fiber-optic probe has been used to analyze chemical agents and other toxic chemicals in sealed glass containers. These containers include ampoules and bottles that are contents of chemical agent identification sets (CAIS) developed for use in training military personnel in chemical agent identification, safe handling, and decontamination. Real-time nonintrusive analysis of these sets is required so that the items containing chemical agents can be identified for proper disposal. This paper details the laboratory measurement of Raman spectra of CAIS chemicals, the determination of detection limits for mustard gas and lewisite in chloroform, and the analysis of CAIS items in the field.

The principle of operation and characteristics of diode lasers are briefly reviewed and critically compared to those of other lasers in regard to use as excitation light sources for laser Raman spectroscopy. Relative to other lasers frequently used for Raman spectroscopy, diode lasers have the advantages of smaller size, less interference from most sample fluorescence (compared to green, blue and UV lasers), greater efficiency, lower heat generation, less need for support equipment, potentially longer operating lifetime, virtually continuous tuning capability over approximately 30 nm, and lower cost. The disadvantages include generally lower power, smaller Raman cross section (because of restriction to near-infrared and infrared wavelengths), poor detection for large Stokes Raman shifts, decreased wavelength stability (“mode hopping”), greater beam divergence, decreased human-eye visibility, and (in some cases) decreased coherence. To date, diode lasers have only been used in conjunction with a relatively few Raman studies involving surface-enhanced Raman spectroscopy and remote optical fiber probes. As they become more powerful, stable, and coherent, diode lasers are expected to become more prominent in Raman spectroscopic studies, especially those requiring portable remote systems for process monitoring and selected environmental applications. The ease of use and handling of diode lasers will lend themselves to integration into turn-key Raman system packages which will be used as a routine analytical tool by general chemists.

The recommendations for the management of osteoarthritis (OA) of the knee firstly proposed by the EULAR in 2000, have been updated in 2003. One of the most important objectives of the expert charged to provide these recommendations was their dissemination. Thus, the information generated may be used by each individual country to produce their own set of management guidelines and algorithms for treatment in primary care. The Italian Society of Rheumatology (SIR) and the Italian League against Rheumatism (LIMAR) have organised a Consensus on the EULAR recommendations 2003 with the aim to analyse their acceptability and the applicability according to our own experience and local situations in the Italy. The results of this Consensus have demonstrated that a large majority of the EULAR recommendations are endorsed by the Italian experts. Furthermore, the final document of the Italian Consensus clearly indicated the need that the specialists involved in the management of knee OA strongly encourage the dissemination of the EULAR 2003 recommendations also in Italy.

A photoelectrochemical approach is employed to fabricate exceptionally smooth low-pitch grating structures consisting of polished single crystals of (100) oriented n-GaAs in a sawtooth profile. The depth of the edged features is controlled by monitoring the total coulombs passed, and the rate of etching is precisely controlled by the light intensity, minimizing diffusional gradients in the liquid which may impair the uniformity. Symmetrical grooves spaced 10 microns apart will have a depth of 7.14 microns, and typically, 10-20 percent less total charge is required.

Raman spectra have been observed to within less than 200 cm−1 of the Rayleigh line through the use of a holographic Bragg diffraction (HBD) filter. The HBD filter has a very high optical density (5.8 OD) while maintaining a relatively high and flat transmission in the region >200 cm−1. Utilization of an HBD filter allowed the observation of Raman spectra with a compact 0.125-mm spectrograph. Spectra of solid, liquid, and surface-enhanced Raman (SER) samples have been demonstrated with the HBD Raman system.

In this paper we describe BioLert II, an ultraviolet laser induced fluorescence (LIF) biological agent monitor for detecting low concentrations of pathogens amid the ambient aerosol. BioLert II measures the fluorescence intensity and size of individual particles, and computes the Degree of Threat (DoT), an indicator of the likelihood that a particular threat material has appeared amid the recently sampled aerosol background. Performance is quantified using Receiver Operating Characteristic (ROC) curves, which plot the relationship among threat concentration, probability of detection, and false alert rate. We present BioLert II ROC curves for the detection of several simulated biological agents in an environment of interest.

Diffuse large B cell lymphoma (DLBCL) is the largest subtype of non-Hodgkin's lymphomas (NHLs) and is characterized by relatively frequent extranodal presentation. In these cases, the most common extranodal localizations are stomach, CNS, bone, testis and liver. Simultaneous detection of multiple extranodal involvement at presentation is quite uncommon, with the majority of these cases characterized by gastric or intestinal disease localization. Retrospective analysis concerning multifocal extranodal NHLs never pointed out disease features such as those described here. We report a patient with an unusual presentation of DLBCL, characterized by adrenal and renal involvement, associated with symptoms and signs of the cold agglutinin disease and a hypercoagulable state. Subsequently, computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning disclosed a rapidly extensive spread to nodes and bones. Cytofluorimetric analysis of a renal specimen showed medium-to-large lympho-monocytoid elements positive for CD20 with monoclonal expression of immunoglobulin kappa light chain. Histopathological examination confirmed a renal CD20 positive DLBCL localization.

The recommendations for the management of osteoarthritis (OA) of the hip were proposed by EULAR in 2005. Among the most important objectives of the expert charged to provide these recommendations were their wide dissemination and implementation. Thus, the information generated can be used by each individual country to produce their own set of management guidelines and algorithms for treatment in primary care. According with that previously executed for the EU-LAR recommendation 2003 for the knee, the Italian Society of Rheumatology (SIR) has organised a Consensus on the EULAR recommendations 2005 for the management of hip OA. To obtain an acceptability as large as possible, the group of experts was composed by many physicians interested in the management of hip OA, including Orthopaedics, Rheumatologists, Physiatrists, and General Practitioners. Main aim of the Consensus was to analyse the acceptability and applicability of the recommendations according to own experience and local situations in the Italy. The results of this Consensus have demonstrated that a large majority of the EULAR recommendations are endorsed by the Italian experts. Furthermore, the final document of the Italian Consensus clearly indicated the need that the specialists involved in the management of hip OA strongly encourage the dissemination of the EULAR 2005 recommendations also in Italy.

OBJECTIVE: To study in parallel the outflow of the sympathetic nervous system (SNS) and the hypothalamic-pituitary adrenal (HPA) axis tone in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: 32 patients with SLE, 62 with RA, and 65 healthy subjects (HS) were included. To measure the tone of the HPA axis, plasma ACTH and serum cortisol were determined. Serum neuropeptide Y (NPY) was used to evaluate the sympathetic outflow. RESULTS: Patients with SLE had increased NPY levels in comparison with HS, irrespective of prior prednisolone treatment (p

Summary Background : The potential clinical implications of autoimmunity during treatment with infliximab are unclear. Aim : To determine the frequency and correlation of autoantibody formation in patients with Crohn's disease treated with infliximab in a routine clinical setting. Methods : Sixty-three patients with refractory/inflammatory (31) and/or fistulising Crohn's disease (32), received an infliximab infusion at a dose 5 mg/kg in weeks 0, 2 and 6, and were evaluated for the development of antinuclear, anti-double-stranded DNA, anti-Sm, anti-RNP, anti-SSA, anti-SSB and antihistone antibodies. The correlates with pharmacological treatments, the response to infliximab and adverse events were evaluated. Results : Antinuclear antibodies were found in five of the 63 patients (8%) at baseline and in 26 (42%) after 10 weeks (P

We report a patient with longstanding systemic lupus erythematosus (SLE) who developed pure red cell aplasia (PRCA). This condition is rare in connective tissue diseases and is reported in 32 previous cases of SLE in literature. Our patient recovered, apparently in response to treatment with high dosage of corticosteroids, but relapse occurred when the prednisone dosage was tapered down to 10 mg/day. The patient was successfully treated with cyclosporin A with no recurrence of the disease in the last 2 years.

In the last few years there are increasing evidences suggesting that osteopenia and osteoporosis are frequent among HIV positive patients. It is still not clear if the bone demineralization is a direct consequence of viral infection or of the antiretroviral drugs. Studies to date therefore give conflicting results. We performed a study to evaluate the prevalence of osteopenia and osteoporosis in HIV positive patients, either untreated or receiving antiretroviral therapy, to asses the frequency of these conditions and the role of antiretroviral drugs. © 2004 Elsevier SAS. All rights reserved.

Drug-induced lupus is a syndrome which share symptoms and laboratory characteristics with the idiopathic systemic lupus erythematosus (SLE). The list of medications implicated as etiologic agents in drug-induced lupus continues to grow. The terms used for this condition are lupus-like syndrome, drug-induced lupus erythematosus (DILE) and drug related lupus. More than 80 drugs have been associated with DILE. The first case of DILE was reported in 1945 and associated with sulfadiazin. In 1953 it was reported that DILE was related to the use of hydralazine. Drugs responsible for the development of DILE can divided into three groups, but the list of these drugs is quite long because new drugs are included yearly in the list. The syndrome is characterised by arthralgia, myalgia, pleurisy, rash and fever in association with antinuclear antibodies in the serum. Recognition of DILE is important because it usually reverts within a few weeks after stopping the drug.

To validate a translated Italian version of the Fibromyalgia Impact Questionnaire (FIQ).The Italian version of the FIQ was administered to 50 patients affected by fibromyalgia (FM) (48 patients filled out the questionnaire again 10 days later) together with the Italian version of the Stanford Health Assessment Questionnaire (HAQ), the Medical Outcomes Survey Short Form-36 (SF-36), and a tender point count (TPC) obtained by summing the score (0-3) of each tender point tested by thumb palpation. All patients were asked about the severity of pain today (10 cm visual analog scale) and the duration of symptoms. Test-retest reliability was assessed using Spearman correlations. Internal consistency was evaluated with Cronbach's alpha of reliability. Construct validity of the FIQ was evaluated by correlations between the HAQ and subscales of the SF-36 as well as the TPC.The mean duration of symptoms was 6.5 years and the mean age of the participants was 57.4 years. Test-retest reliability was between 0.74 and 0.95 for physical functioning as well as for the total FIQ and other components. Internal consistency was 0.90 for the overall FIQ. Significant correlations were obtained between the FIQ items, the HAQ and the SF-36.The Italian FIQ is a reliable and valid instrument for detecting and measuring functional disability and health status in Italian patients with FM.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Treatment of the disease has contributed dramatically in the long-term survival of the patients and now SLE has become a chronic inflammatory disorder. Present data suggest 5, 10 and 20-year survival rates of 93%, 85% and 68% respectively. Accelerated atherosclerosis and early coronary artery disease have become important causes of death and hospitalisation in SLE patients. Many cardiovascular risk factors can be considered: disease activity (particularly kidney involvement), sedentary life (in nearly 70% of the patients), hyperlipidemia, antiphospholipid antibodies, serum homocysteine and many others. Although traditional risk factors are operative in patients with SLE, the risk for myocardial infarction was increased 8.3 folds after controlling these factors in a study, suggesting that SLE itself was the strongest risk factor for cardiovascular disease. Lipid abnormalities may play a major role in increasing cardiovascular risk in SLE patients who are characterized by elevated triglycerides, very low-density lipoprotein cholesterol (VLDL-C), reduced levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A-1. Anticardioli-pin antibodies may influence lipid levels in SLE; in particular SLE patients with IgG anticardiolipin antibodies had significantly lower HDL-C compared with patients with no anticardiolipin antibodies. Elevation of serum homocysteine is observed in 15% of SLE patients and is significantly associated with the development of stroke and arterial thrombotic events. The antiphospholipid syndrome (APS) is an acquired thrombotic disorder characterised by recurrent venous or arterial thrombosis or recurrent miscarriages, or both, associated with the presence in the serum of IgG or IgM anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC). APS may occur as a primary disorder (PAPS) or associated with connective tissue diseases, mainly systemic lupus erythematosus (secondary APS). Primary and secondary APS are both associated with a significant increase of cardiovascular risk.

Objective: To validate a translated Italian version of the Fibrofatigue Scale (FFS). Methods: The Italian version of FFS was administered to 60 patients affected by fibromyalgia (FM) (57 patients were interviewed again 10 days later) together with the Italian version of the Fibromyalgia Impact Questionnaire (FIQ), the Stanford Health Assessment Questionnaire (HAQ) and the Medical Outcome Survey Short Form-36 (SF-36). All patients were asked about the severity of pain today (10-cm visual analogue scale) and the duration of symptoms. Test–retest reliability was assessed using Spearman correlations. Internal consistency was evaluated with Cronbach's α of reliability. Construct validity of the FFS was evaluated by correlations among the FFS, the FIQ and the subscales of the SF-36. Results: Mean duration of symptoms was 7.6 years, and mean age of participants was 56.3 years. Test–retest reliability was between 0.70 and 0.95 for the single items as well as for the total FFS and other components. Internal consistency was 0.90 for the overall FFS. Significant correlations were obtained between the FFS items and the SF-36. Conclusions: The Italian FFS is a reliable and valid instrument for detecting and measuring functional disability and symptoms severity in Italian patients with FM.

To evaluate hypersomnolence in patients affected by fibromyalgia syndrome.Thirty consecutive patients affected by fibromyalgia syndrome (FMS) (28 F) completed a sleep questionnaire and underwent the following evaluations: lung function tests; polysomnography; the Epworth sleepiness scale (ESS), which measures sleep complaints and daytime hypersomnolence; and the visual analogical scale (VAS) to detect subjective pain, fatigue, anxiety and depression.The FMS patients were divided into two groups based on their ESS score. Patients complaining of daytime hypersomnolence had a higher number of tender points (15 +/- 2 vs. 12 +/- 1, p0.01), a higher subjective pain score (72 +/- 15 vs. 52 +/- 13, p0.05), and more fatigue (p0.05). The diffusing capacity of the lung (Tlco) was more impaired and the occurrence of periodic breathing was higher. FMS patients complaining of daytime somnolence had significantly less efficient sleep than the FMS patients with no daytime somnolence (p0.05), i.e. a lower proportion of stage 3 sleep (5 +/- 2% vs. 12 +/- 3%; p0.001), stage 4 sleep (1 +/- 0.5% vs. 4 +/- 1%; p0.001), and twice as many arousals per hour of sleep (p0.01). The respiratory pattern of FMS patients with hypersomnolence showed a higher occurrence of periodic breathing (p0.05). The short length of apneas and hypopnoeas did not affect the apnea/hypopnea index (5.1 +/- 3 vs. 7 +/- 4; ns), but FMS patients with daytime hypersomnolence had a greater number of desaturations per hour of sleep (11 +/- 6 vs. 6 +/- 5; p0.05). Pulmonary volumes did not differ between the two groups. The EES score was significantly correlated in FMS patients, and even more markedly in the FMS patients with hypersomnolence, TLco, A/I, and disease duration. The ESS score was correlated significantly with the number of tender points only in FMS patients with daytime hypersomnolence.The occurrence of daytime hypersomnolence in FMS patients is linked to a greater severity of fibromyalgia symptoms and to more severe polysomnographic alterations.

Portable fiber-optic Raman systems are being used to analyze chemical agents and other toxic chemicals in sealed glass containers. These containers include ampoules and bottles that are contents of chemical agent identification sets (CAIS) developed for use in training military personnel in chemical agent identification, safe handling, and decontamination. Real-time nonintrusive analysis of these sets is required so that the items containing chemical agents can be identified for proper disposal. This paper details the laboratory measurement of Raman spectra of chemical agents, Raman scattering cross sections of chemical agents, and the analysis of CAIS items in the field.

This chapter describes the use of wavenumber standards for the calibration of Raman instruments. Methods using both The American Society for Testing and Materials (ASTM) Raman shift standard, which was developed to provide accurate wavenumber shifts from readily available commercial materials, and the use of atomic based lines are presented. The Raman shift standard materials have an advantagein that they can then be utilized to calibrate any Raman spectrometer, including spectrometers that use variable excitation sources. They provide an easy way to routinely calibrate an instrument using the actual collection geometry of the apparatus. The use of atomic based lines can provide a more accurate calibration of a spectrometer. Raman shift standard, calibration, wavenumber, atomic lines, ASTM, 4-acetamidophenol.

Several applications of Raman spectroscopy in the forensic sciences have recently been demonstrated, but few have involved the analysis of paints. Undoubtedly, this is a reflection of the sample degradation problems often encountered when a visible or near-infrared laser is focused on a light-absorbing matrix. In this study, a dispersive CCD Raman spectrometer (785 nm) was used in a configuration which collected scattered light from an excitation region 3 mm long and 80 microm wide, instead of from a focused spot. Sample degradation was not observed, and Raman spectra of automotive paints of all colors were readily obtained. Most of the paints analyzed were U.S. automobile original finishes (1974 to 1989) from the Reference Collection of Automotive Paints, and the inorganic pigments examined were those which had been identified previously by infrared spectroscopy in finishes from this collection. Prominent peaks of rutile were observed in Raman spectra of light-colored nonmetallic finishes for both monocoats and basecoat/clearcoat systems, and the rutile peaks are readily distinguished from those of anatase. The lead chromates (Chrome Yellow, Molybdate Orange, and silica-encapsulated versions of the two) are the strongest Raman scatterers among the pigments examined, and Chrome Yellow was identified by Raman spectroscopy in several yellow and orange nonmetallic monocoats for which infrared absorptions of this pigment were not observed. Raman spectroscopy also provides an unequivocal means to distinguish Chrome Yellow from Molybdate Orange. This is particularly helpful for the analysis of paints containing light pigment loads or encapsulated pigments since the two formulations cannot be differentiated by infrared spectroscopy in such cases. The iron-containing pigments, ferric oxide, hydrous ferric oxide, and Prussian Blue, are relatively weak Raman scatterers, but peaks of hydrous ferric oxide and Prussian Blue were observed in spectra of paints containing heavy pigment loads. Because no sample preparation is required. Raman spectroscopy provides an excellent means to rapidly screen reference panels for the presence of certain pigments, and some examples of the differences in Raman spectra which occur for paints having similar colors are presented.

Background YKL-40 or gpl-39 is a surface glycoprotein of connective tissue cells in particular of monocytes, fibroblasts, synoviocytes and chondrocytes. According to some Authors, being augmented in serum of rheumatoid arthritis (RA) and, to a lesser extent, of osteoarthritis (OA) it may correlate with the degree and the speed of cartilage degradation. Objectives To better evaluate if this is true or if this marker is mainly an inflammation index, we have investigated a group of RA patients correlating YKL-40 serum values with some of the clinical parameters of the disease most widely used in literature (swollen or painful joint count, HAQ, PCR, Ra-test, ESR, Rx score of the hands, DAS 28). Methods We have evaluated 52 consecutive patients (43 F, 9 M) with RA according to the ACR criteria mainly in the 2nd (22) or 3rd (25) functional class of Steinbrocker. Their mean age was 59.7 years (33–86) and the mean disease duration 13.6 years (1–35). The YKL-40 was determined in serum according to the ELISA sandwich method of Harvey et al, 1998 (normal range: 25–95 ng\ml); all the patients (pts) were previously visited and all the parameters listed above measured. Moreover the Rx score of the hands was calculate according to the method of Kaye, 1987, slightly modified. The significance of the correlations were evaluated with the Spearman test. Results The mean (± SD) serum values of YKL-40 was 147.84 (± 97.47) ng\ml (normal range: 25–95 ng\ml). The correlations with the parameters listed above were those shown in the following Table 1. Swollen joint count, Rx score and Ra-test showed a still less significant correlation with the marker investigated. Conclusion Since YKL-40 in RA serum seems to better correlate with PCR, DAS 28 and painful joint count respectively, in our opinion it behaves more like an activity marker of the disease (perhaps of synovitis) rather than of cartilage degradation as claimed by some Authors. Despite this limitation, further studies are needed to evaluate its potential prognostic activity as predictor of joint lesions in RA. References Harvey S, et al. Chondrex: a new marker of joint disease. Clin Chem. 1998;44:509–16 Wollheim FA. Markers of disease in RA. Curr Opin Rheumatol. 2000;12:200–4

Background Objectives To evaluate hypersomnolence in patients affected by fibromyalgia syndrome. Methods Thirty consecutive patients affected by fibromyalgia syndrome (FMS) (28 F) underwent a general sleep questionnaire, the Epsworth sleepiness scale (ESS), formal polysomnography, and lung function tests. Results Patients complaining of daytime hypersomnolence had a higher number of tender points (15 ± 2 vs 12 ± 1, p FMS patients who referred daytime somnolence slept significantly less efficiently than the FMS with no day time somnolence (p Conclusion The occurrence of daytime hypersomnolence in FMS patients, is linked to a greater severity of fibromyalgia symptoms and to a more severe polisomnographic alterations.

Background Helycobacter pylori is present in about fifty percent of patients with NSAIDs associated gastric lesions. However, studies on the interaction between H. pylori and the occurrence of NSAIDs gastrotoxicity have yielded conflicting results. Objectives To investigate the correlation between H. pylori infection and the development of NSAIDs related gastric lesions. Methods Data were collected during our double blind clinical and gastroscopic study on the treatment of rheumatoid arthritis with diclofenac or amtolmetinguacyl. A total of 64 patients, aged 18–80 years, suffering from rheumatoid arthritis were randomised to diclofenac (50 mg tid) or amtolmetinguacyl 600 mg bid) for 4 weeks. Clinical and endoscopic evaluation were performed at baseline and at the end of the treatment. The gastroduodenal mucosa was graded according to the Lanza scale, and H. pylori status was assessed at baseline by histology (2 biopsy samples in the antrum, one at the augulus and two in the body of the stomach) and by rapid urease test (one sample in the gastric antrum). Results All but one of the patients reached the final visit and 59 underwent endoscopy. H. pylori infection was detected in 30 of the 59 patients (51%); this prevalence is not significantly different from the age-adjusted rate for control populations in western countries and is consistent with previous reports in rheumatoid arthritis and in arthritides of different aetiology. The gross appearance of gastroduodenal mucosa was graded as follows: grade 0, normal mucosa; grade 1, mucosal haemorrhage only; grade 2, one or two erosions; grade 3, numerous areas (3–10) of erosions; grade 4, large number of erosions (> 10) or an ulcer. Considering together patients with endoscopic grading 0–1–2 (normal or minimal lesions) and grading 3–4 (numerous erosions or ulcer), 6/30 (20%) of the H. pylori positive patients and 9/29 (31%) of the H. pylori negative patients had endoscopic scores of 3 or 4 (p Conclusion In this study we did not find any statistically significant correlation between H. pylori status and NSAIDs gastrolesivity. However, most gastric lesions (60%) occurred in H. pylori negative patients, suggesting that the presence of the infection is not a risk factor for the occurrence of NSAIDs related gastric lesions.

In this review, we summarize the significant progress that has been made in the identification of melanoma-associated antigens (MAA) recognized by cytotoxic T-lymphocytes (CTL). These antigens belong to three main groups: tumor-associated testis-specific antigens (e.g. , MAGE, BAGE, and GAGE); melanocyte differentiation antigens (e.g., tyrosinase, Melan-A/MART-1); and mutated or aberrantly expressed molecules (e.g, CDK4, MUM-1, beta-catenin). Although strong CTL activity may be induced ex vivo against most of these antigens, often in the presence of excess cytokines and antigen, a clear understanding of the functional status of CTL in vivo and their impact on tumor growth, is still lacking. Several mechanisms are described that potentially contribute to tumor cell evasion of the immune response, suggesting that any antitumor efficacy achieved by immune effectors may be offset by factors that result ultimately in tumor progression. Nevertheless, most of these MAA are currently being investigated as immunizing agents in clinical studies, the conflicting results of which are reviewed. Indeed, the therapeutic potential of MAA has still to be fully exploited and new strategies have to be found in order to achieve an effective and long-lasting in vivo immune control of melanoma growth and progression.

Imaging methodologies present some of the most exciting new frontiers in the biological and medical sciences. Raman spectroscopic imaging combines the power of chemical imaging with the spatial resolution for translating microscopic spectroscopic information into statements relevant to biological and medical function. Imaging results will be presented using mapping, dielectric filters, and liquid- crystalline tunable filters at different excitation wavelengths for selectively determining the spatial distribution of biomaterials in a variety of biological systems.

Six cases of retroperitoneal fibrosis, each with a different pathogenesis and unusual localization were observed from 1980 to 1996. Four patients had had previous surgery for a neoplasm, one patient had idiopathic retroperitoneal fibrosis, and the last patient was hardly classifiable due to the complexity of the clinical pattern. The mean survival in 3 patients with malignant retroperitoneal fibrosis was 7 months. Two patients treated with medical therapy are still alive and in good clinical condition. The aspecificity of the symptoms makes early diagnosis difficult. CT and NMR are essential procedures for differential diagnosis of abdominal masses. Histology differentiates benign from malignant retroperitoneal fibrosis. The choice between medical or surgical therapy depends on the general condition of each patient.

The local tolerability, safety and efficacy of meloxicam 15 mg suppositories were compared with piroxicam 20 mg suppositories over a 3-week period in a single-blind, randomized study in patients with osteoarthritis. Patients were randomized 2:1 to receive meloxicam (n = 216) or piroxicam (n = 109). More than 90% of patients and investigators assessed local tolerability of both treatments as good or very good (primary endpoint). There was no significant difference between the groups. Global efficacy was reported by approximately 80% of patients in both groups to be good or very good. Pain on movement and at rest and joint mobility showed statistically significant improvements compared with baseline with both meloxicam and piroxicam; there were no statistically significant differences between treatment groups. Piroxicam and meloxicam suppositories were equally well tolerated, with no serious adverse events recorded in either treatment group. Local adverse events occurred in 11.9% of patients receiving piroxicam and 6.9% of those receiving meloxicam. Overall, gastrointestinal adverse events were the most frequent of all 11.9% of piroxicam-treated patients). In both groups, about 90% of global tolerability assessments were classified, by the investigator and the patient, as either very good or good. In conclusion, meloxicam 15 mg suppositories showed excellent local tolerability accompanied by good safety and efficacy in osteoarthritis, which was comparable to that of an established non-steroidal anti-inflammatory drug (NSAID) administered by the rectal route, and to that previously observed with oral formulations of meloxicam 15 mg.

Increased restrictions on the enantiomeric purity of pharmaceuticals underscore the need for improved analytical techniques to quantitate chiral purity. The method of scattered circularly polarized Raman optical activity (SCP ROA) is examined as a potentially useful analytical technique. Preliminary studies revealed SCP ROA measurements were reproducible to within current experimental noise limits and displayed the expected linear decrease in SCP ROA with increasing racemization of the enantiomeric mixtures. Minimal interference in SCP ROA signal was observed when either an achiral or another chiral entity was present in a mixture. The advantages of spectral subtraction techniques were demonstrated for separation of SCP ROA signals when multiple chiral entities are present. SCP ROA has been shown to be capable of quantitative analysis and is capable of simultaneous identification of multiple enantiomeric species. This is significant since traditional optical activity measurements, such as polarimetry and circular dichroism, are of limited value on mixtures where the impurities are not quantitatively defined.

Chondroprotective agents represent a model for basic therapy of osteoarthritis (OA), thanks to their activity directed towards the protection and repair of articular cartilage. One of the most recent compounds capable of interfering with the pathogenic mechanisms of OA is galactosamino-glycuronoglycan-sulfate (GGGS), a highly depolymerized glycosaminoglycan with favourable chondroprotective and anti-inflammatory properties. The present paper describes the experience with GGGS given to a group of patients with symptomatic OA of the knee as compared to a parallel group treated with placebo. The drug (or placebo) was administered in two series of 25 intramuscular injections each over a period of 11 months, and four successive evaluations of treatment were made at various times during this period, and a fifth evaluation one month after the suspension of treatment to better evaluate the permanence of the therapeutic effect. The results obtained showed significant improvements on pain, algofunctional index and consumption of NSAIDs only in the group treated with GGGS. The drug was well tolerated and no reduction of dosage or drop-out from therapy were required. The favourable clinical effects and the patients' good compliance make GGGS a useful drug for successful chondroprotective treatment of OA.

Spectroelectrochemical technologies and instrumentationfor environmental and process monitoringMichael M. Carrabba, Kevin M. Spencer, Robert B. Edmonds and R. David RauhEIC Laboratories, Inc.1 1 1 Downey Street, Norwood, MA 02062andJohn W. Haas, IllOak Ridge National Laboratories, Health and Safety DivisionP.O. Box 2008, Oak Ridge, TN 3783 1-6383ABSTRACTThe importance of techniques to sense and monitor the environment are becoming increasingly more

Raman spectroscopy is a powerful noninvasive tool for elucidating chemical structure. Like infrared spectroscopy, it has many potential practical applications, such as process monitoring, environmental sensing, clinical analysis, forensic identification, and as a detector for use with analytical instruments. Until recently, however, Raman has been considered mainly in the context of basic research. The present generation of high performance Raman instruments tend to be large, complex and expensive, and thus have been of primary interest only to specialists in the field. This paper will discuss the development of a compact Raman spectrometer system consisting of a diode laser, fiber optics of excitation and collection, and a compact spectrograph with charge coupled device (CCD) detection.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

This paper will evaluate the potential applications of SERS for bio- and biomedical sensing. The emphasis willbe on technologies which will allow the development ofcost effective SERS instrumentation. Potential techniques which can be adapted to fiber optic based sensing will also be discussed.

Photoelectrochemical etching of high aspect ratio mask-defined grooves in (100)n-GaAs is shown to be dependent on both crystallographic orientation and doping level. Structures etched along the (011) direction produced V grooves, showing that the (111)Ga surface is a stop plane with respect to oxidation by photogenerated holes. Other orientations etch more isotropically. In all cases, undercutting of the mask is associated with lateral diffusion of holes due to slow kinetics of consumption by the interfacial reaction. This effect is minimized in highly doped crystals, where high quality vertical walled gratings can be produced using visible light with aspect ratios of >10:1.

We report the results of a laser‐saturated fluorescence study of the S2←S0 000 vibronic bands of two conformers of guaiazulene in a supersonic jet. Photophysical parameters were derived from the saturation study using a three‐state kinetic model which explicitly accounted for heterogeneous broadening. Since heterogeneous broadening (rotational and Doppler) is significant in heavy polyatomics, this method could become important in extending the utility of saturation studies beyond the atomic and diatomic systems to which the technique has usually been applied. To assess the utility of our kinetic model, we compared the results to those obtained with another commonly used kinetic model which ignores all frequency dependence in a spectroscopic resonance. We also collected direct absorption and unsaturated fluorescence excitation spectra in the jet, and extensive laser beam diagnostics, to parametrize the kinetic model and to provide an independent determination of the absorption cross section. The kinetic fi...