Influenza Vaccination Coverage Rate for Medical Staff: Influence of Hospital-Based Vaccination Campaign.

Despite intensive recommendations, influenza vaccination rate in medical staff in Poland ranges from about 20 % in physicians to 10 % in nurses. The objective of this work was to assess the influence of hospital influenza vaccination campaign directed toward health care workers, combined with dispensing free of charge vaccine, on vaccination rate. The campaign was conducted by the Hospital Infection Control Team of the Czerniakowski Hospital in Warsaw, Poland, separately for physicians, nurses, and physiotherapists. Overall, 37 % of medical staff were vaccinated, including 55 % of physicians and 21 % of nurses. Concerning physicians, the greatest vaccination rate was in the orthopedic (80 %) and ophthalmology units (73 %), whereas the lowest rate was in the intensive care (22 %) and neurology units (20 %). Concerning nurses, the greatest vaccination rate was in those working in the outpatient (40 %) and emergency units (29 %), whereas the lowest rate was in the ophthalmology (6 %) and surgery units (11 %). We conclude that the professional knowledge campaign combined with the incentive of free of charge vaccine substantially raises the vaccination rate among medical staff.

Lund-Mackay System for Computed Tomography Evaluation of Paranasal Sinuses in Patients with Granulomatosis and Polyangiitis.

Granulomatosis with polyangiitis (GPA), a disease capable of affecting any organ, most often acts upon the upper respiratory tract. Diagnostic imaging is primarily represented by computed tomography (CT) of paranasal sinuses. The aim of this study was to define the characteristic changes in paranasal CT in patients with GPA and to evaluate diagnostic usefulness of the Lund-Mackey scoring system (L-M System). The study encompassed 43 patients with GPA of the mean age of 47.7 ± 12.8 years who were treated topically with mupirocin. We found that inflammation occurred mainly in the maxillary sinuses (72%). The mean L-M score was 5.8 ± 6.1. The right maxillary sinus had the highest percentage (12.6%) of score hits of 1, i.e., partial opacification and the left ostiomeatal complex had the highest percentage (7.6%) of score of 2, i.e., complete opacification or obstruction. The following changes were the most characteristic for GPA: sinus mucosal thickening, widespread bone damage, and osteogenesis. We conclude that the long-term topical mupirocin treatment of GPA may inhibit nasal bone damage, but also may led to permanent rhinological changes of the rhinosinusitis type. The Lund-Mackey staging system is a useful diagnostic imaging option in GPA patients.

Subglottic and tracheal stenosis due to Wegener's granulomatosis.

Wegener's granulomatosis (WG) is characterized histologically by necrotizing granulomatous angitis that most commonly involves the upper, lower respiratory tract and kidneys, but may affect any organ system. Otolaryngological manifestations are frequent and diverse but subglottic stenosis and tracheal stenosis are less common. The aim of the study was to assess the clinical features and the response to treatment in WG patients with subglottic or tracheal stenosis. The disease activity at the time of examination was scored in 55 patients with WG (29 females, 26 males) according to clinical, serological, radiological and bronchoscopic findings: subglottic and tracheal stenosis were observed in 9% and 5% of WG patients, respectively. CT scans of the larynx and trachea showed mucosal thickening extended 3-4 cm below the vocal cords in three and the thyroid cartilage in one patient. The degree of narrowing of the axial luminal diameter ranged 50-90%. Mechanical dilation of the stenosis and long-acting local corticosteroids may be of therapeutic benefit, along with conventional immunosuppressive treatment.

Atherosclerotic factors in PR3 pulmonary vasculitis.

Autoimmune disease such as systemic lupus erythematosus or rheumatoid arthritis are connected with higher risk of atherosclerosis and cardiovascular complications and mortality. This results from inflammatory damage to the vessel wall by vasculitis. The aim of the present study was to evaluate whether patients with Wegener's granulomatosis (WG) and pulmonary involvement have an increased prevalence of atherosclerotic disease as characterized traditional risk factors. Twenty one patients with WG in remission and 15 control subject were entered to the study. Traditional risk factor for cardiovascular disease such as hyperglycemia, hypertension, smoking, obesity, and dyslipidemia were assessed. Both systolic and diastolic blood pressure were higher in WG patients (p<0.025). Total cholesterol, LDL and TG levels were markedly elevated in 18 of the 21 in pulmonary WG patients. Compared with controls, plasma levels of hsCRP were raised in WG patients; 3.68 (0.79-9.75) mg/l vs. 0.14 (0.12-0.59) mg/l (p<0.01). We conclude that non-pharmacological and pharmacological treatments of traditional risk factors are crucial to prevent cardiovascular disease in WG patients and thus should be part of therapy to control WG activity and damage caused by it.

Influence of sera from interstitial lung disease patients on angiogenic activity of mononuclear cells.

Chronic inflammation stimulates of neovascularization. The aim of this study was to evaluate the effect of sera from interstitial lung diseases (ILD) patients on angiogenic capabilities of different subsets of mononuclear cells. Serum samples were obtained from 22 patients with sarcoidosis, 20 with hypersensitivity pneumonitis, 20 with idiopathic pulmonary fibrosis, 9 with systemic sclerosis, 6 with pulmonary Langerhans cells histiocytosis, and from 20 healthy volunteers. Animal model of leukocyte induced angiogenesis assay was used as an angiogenic test. The pattern of angiogenic reaction was different in different diseases. Sera from systemic sclerosis and pulmonary Langerhans cells histiocytosis patients exerted inhibitory effects on angiogenesis, but sera from sarcoidosis, hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis patients stimulated angiogenesis. Sera from sarcoidosis and pulmonary Langerhans cells histiocytosis primed monocytes for the production of angiogenic factors. The number of microvessels created after incubation of mononuclear cells depleted of monocytes with sera from systemic sclerosis patients significantly decreased. We conclude that the role of monocytes in the modulation of angiogenesis varies depending on the type of ILD. Sera from sarcoidosis stimulate and from pulmonary Langerhans cells histiocytosis patients inhibit neovascularization induced by monocyte mediators. Sera from systemic sclerosis inhibit angiogenesis induced by lymphocyte products.

Angiogenic activity of sera from interstitial lung disease patients in relation to angiotensin-converting enzyme activity.

The role of angiogenesis in the pathogenesis of interstitial lung diseases (ILD) is unknown. Angiotensin-converting enzyme (ACE) is a marker of sarcoidosis activity and may modulate angiogenesis. The aim of this study was to examine the relationship between ACE activity in ILD patients' sera and their effect on microvessels formation in an in vivo model of leukocyte-induced angiogenesis. The study population consisted of 77 sarcoidosis patients, 22 idiopathic pulmonary fibrosis patients, 16 bird fanciers lung patients, eight silicosis patients and 14 healthy donors. Serum ACE activity was assayed by spectrophotometric method. As an angiogenic test, a leukocyte-induced angiogenesis assay in an animal model was used. Sera from interstitial lung disease patients significantly stimulated angiogenic activity of mononuclear cells compared with healthy donors (p < 0.001). The highest ACE serum activity was measured in sera from the silicosis patients, and lowest in sera from the sarcoidosis and IPF patients. A significantly lower serum ACE activity was detected in the bird fanciers lung patients. Serum angiogenic activity of ILD patients measured by angiogenesis index negatively correlated with ACE serum activity (r = ;-0.52; p < 0.01). This correlation was highest in the sarcoidosis group (r = -0.6; p < ). Sera from ILD patient constitute the source of factors modulating angiogenesis.

Rhinologic and sinonasal changes in PR3 ANCA pulmonary vasculitis.

BACKGROUND: Over 70-95% patients with PR3 ANCA pulmonary vasculitis present with upper respiratory tract symptoms or sings. Nasal cavity usually presents with obstruction and chronic refractory infections (rhinosinusitis) which commonly manifest as bloody discharge or crusting obstruction. Mucopurulent discharge may occur in the acute phase or remission, along with other symptoms suggesting sinusitis. Later on, saddle nose deformities can occur due to collapse of the nasal septum. Other common destruction areas are the maxillary ostia, erosion of the tubinates or damage of soft palate. OBJECTIVE: The aim of the study was to characterize pathologies of nasal and sinonasal CT scans in patients with PR3 pulmonary ANCA vasculitis and to establish the CT diagnostic criteria for WG. Between 2005-2009 sinonasal CT visualization was performed in 35 patients (19 female, 16 male) with PR3 ANCA positive WG. RESULTS: Bony destruction of the nasal cavity was revealed in 15 (42.8%), damage or distortion of the paranasal sinuses in 20 (57.1%), the mastoid cells in 7 (20%), and the orbits in 7 (20%) patients. Sclerosing osteitis of the nasal cavity and paranasal sinuses were observed in 11 (31.4%) and in 24 (68.5%), respectively. Bony thickening of the nasal cavity was shown in 5 (14.2%) patients and of the paranasal sinuses in 7 (20%) (unilateral in 2 and bilateral in 5 patients). Seven patients (20%) had orbital masses; all unilateral. Septal perforation was observed in 11 (31.4%) and saddle nose deformity in 7 (20%) patients. CONCLUSIONS: Maxillary sinuses are regions which are most frequently affected during the course of PR3 ANCA pulmonary vasculitis. CT imagines may be a useful supplement to clinical and activity scoring of WG disease with pulmonary involvement.

Angiogenic activity of sera from interstitial lung disease patients in relation to clinical and radiological changes.

OBJECTIVE: Clinical symptoms and radiological changes are useful in monitoring patients with interstitial lung diseases (ILD). Neovascularization participates in the pathogenesis of idiopathic pulmonary fibrosis and other ILD. The objective of the study was to examine the relationships between angiogenic activity of sera from ILD patients and clinical or radiological status. MATERIAL AND METHODS: Serum samples were obtained from 83 patients with sarcoidosis, 31 with idiopathic pulmonary fibrosis (IPF), 29 with hypersensitivity pneumonitis (HP), 16 with collagen diseases with pulmonary manifestation (CD), 13 with scleroderma (SCL), 14 with Wegener's granulomatosis (WG), 12 with pulmonary Langerhans cell histiocytosis (HIS), 12 with pneumoconiosis (PNC), 10 with drug-induced lung disease (DLD), 5 with cryptogenic organizing pneumonia (COP), and from 36 healthy volunteers. As an angiogenic test we used a cutaneous angiogenesis assay according to Sidky and Auerbach. Clinical status was evaluated using a special questionnaire. In all patients chest radiographs were performed. RESULTS: The angiogenic properties of sera from ILD differed depending on the clinical diagnosis. The strongest proangiogenic effect was induced by sera from patients with HP (mean number of new vessels 16.8), CD (16.6), sarcoidosis (16.3), IPF (16.2), and PNC (15.7). In the case of DLD (13.2), the effect was comparable to healthy controls (13.5). In contrast, sera from SCL (mean number of the vessels 10.5) and HIS patients (10.8) significantly inhibited angiogenesis compared with controls. The angiogenic activity of sera from patients with hilar or mediastinal lymph nodes involvement was higher than that of sera from patients with lung fibrosis. There were also differences in the serum angiogenic activity in relation to the severity of dyspnea. CONCLUSIONS: The data showed that sera from ILD patients constitute a source of mediators modulating angiogenesis, but the pattern of reaction is different in various diseases. Sera from HP, sarcoidosis, IPF, and CD patients demonstrated the strongest proangiogenic activity. However, sera from SCL and HIS inhibit angiogenesis. Angiogenic activity of examined sera was related to the clinical and radiological changes.

Co-trimoxazole and prevention of relapses of PR3-ANCA positive vasculitis with pulmonary involvement.

BACKGROUND: Bacterial and viral respiratory tract infections may trigger relapses in patients with PR3-positive vasculitis. Data have suggested that treatment with co-trimoxazole may be beneficial, because this antibiotic could act by eliminating the offending microbe and thereby stopping the initiating stimulus. GOAL AND METHODS: Prospective, randomized, placebo-controlled study of the efficacy of co-trimoxazole given 960 mg thrice weekly for 18 months in preventing relapses in patients with Wegener's granulomatosis (WG) in remission, after treatment with cyclophosphamide and prednisolone was conducted. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, serological, microbiological, and histopathological findings. Sixteen patients were assigned to receive co-trimoxazole and 15 to receive placebo. RESULTS: Seventy five percent of the patients in the co-trimoxazole group remained in remission at 18 months and 55% of those in the placebo group. A proportional hazard regression analysis identified a positive PR3-ANCA test at the start of treatment, chronic nasal crusting, and Staphylococus aureus infection as risk factors for relapse. Furthermore, the analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged disease-free interval. CONCLUSION: Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission.

Clinical implications of serum thrombomodulin in PR3-ANCA-associated vasculitis.

BACKGROUND: Vascular injury is the main mechanism in pathophysiology of PR3-ANCA-associated vasculitis. Soluble serum thrombomodulin (sTM) is a membrane-bound receptor for thrombin expressed by vascular endothelial cells. - OBJECTIVE: The aim of study was to determine the blood levels of sTM in patients with PR3-ANCA-associated vasculitis. MATERIAL AND METHODS: Twenty five patients with Wegener's granulomatosis (WG), 13 with generalized WG and 12 with limited WG, with histologically proven disease, and 15 healthy subjects as a control were investigated. An ELISA for detection of sTM and PR3-ANCA was performed. The disease activity was evaluated according to BVAS and DEI indexes. RESULTS: Significant increases in sTM were found in both active generalized and limited active WG compared with control values: 108 +/- 12, 56 +/- 2, and 12 +/- 4 ng/ml, respectively. Elevated ANCA titer correlated with disease activity, but more weakly than sTM levels did. Elevated sTM concentration is a result of vascular endothelial injury in the course of PR3-ANCA associated vasculitis. CONCLUSIONS: Soluble serum thrombomodulin is a promising, both diagnostic and therapeutic, marker of endothelial cell injury in relation to disease activity and progression in autoimmune disorders, reflecting the degree of endothelial cell damage.

Modulatory effect of sera from patients with various types of pulmonary fibrosis on mononuclear cell induced angiogenesis in relation to pulmonary function.

Angiogenesis plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. Pulmonary fibrosis occurs also in many diseases, such as other types of interstitial pneumonias or drug-induced pulmonary fibrosis. The aim of the study was to examine the effect of sera from patients with various types of pulmonary fibrosis on angiogenesis induced by human mononuclear cells (MNC) in relation to lung functions. The study population consisted of 32 patients with idiopathic pulmonary fibrosis (IPF), 11 patients with drug-induced pulmonary fibrosis (DIPF), 6 with cryptogenic organizing pneumonia (COP), and 20 healthy volunteers. An animal model of leukocyte-induced angiogenesis assay was used as an angiogenic test. Spirometry, whole-body plethysmography, static lung compliance (Cst), and diffusing capacity of the lung for CO (DL(CO)) were performed in all patients. Sera from IPF and COP patients significantly stimulated angiogenic activity of MNC, compared with sera from healthy donors and from DIPF patients (P<0.001). However, sera from healthy donors and DIPF significantly stimulated angiogenic activity of MNC compared with the control group with PBS (P<0.001). In all groups, a decrease in the mean value of Cst and DL(CO) was observed, but no significant correlation between VC, FEV(1), DL(CO), Cst, and angiogenic activity of sera from examined patients was found. Sera obtained from patients with pulmonary fibrosis constitute a source of mediators modulating angiogenesis, but the pattern of reaction is different in various diseases. The strongest reaction is observed in IPF and the weakest one in DIPF. The angiogenic activity of sera did not correlate with the pulmonary function of patients with pulmonary fibrosis.

Angiogenic activity of sera from silicosis and pulmonary Langerhans cell histiocytosis patients in relation to lung function tests.

Angiogenesis has been implicated in the pathogenesis of interstitial lung diseases. A correlation between serum angiogenic cytokines level of patients with idiopathic pulmonary fibrosis and radiographic manifestations or functional pulmonary changes has been described, but the role of angiogenesis in the pathogenesis of other interstitial lung diseases such as silicosis and pulmonary Langerhans cell histiocytosis remains unclear. The aim of the study was to examine the effect of sera from silicosis and pulmonary Langerhans cell histiocytosis patients on angiogenesis induced by human mononuclear cells (MNC) in relation to pulmonary function. The study population consisted of 12 patients with silicosis, 12 patients with pulmonary Langerhans cell histiocytosis (PLH), and 14 healthy volunteers. Spirometry, whole-body plethysmography, static lung compliance (Cst), and diffusing capacity of the lung for CO (DL(CO)) were performed in all patients. As an angiogenic test, leukocyte induced angiogenesis assay according to Sidky and Auerbach was used. Sera from PLH patients exerted a significant inhibitory effect on angiogenesis (P<0.001). Sera from silicosis patients significantly (P<0.001) stimulated angiogenesis compared with sera from healthy donors. However, sera from healthy donors significantly stimulated the angiogenic activity of MNC compared with the control with PBS. The mean value of DL(CO) was significantly lower in the group of patients with PLH compared with patients with silicosis (P<0.05). A significant correlation between angiogenesis index and DL(CO) was observed (P<0.05). No significant correlation between the angiogenesis index and other functional parameters was found. Sera from interstitial lung diseases patients and healthy donors constitute a source of mediators modulating angiogenesis. Sera from silicosis patients stimulate neovascularization but sera from PLH patients exert an inhibitory effect on angiogenesis. A correlation between serum angiogenic activity and DL(CO) was found.

Angiogenic activity of sera from patients with systemic autoimmune diseases in relation to clinical, radiological, and functional pulmonary status.

Systemic autoimmune diseases, such as vasculitis and collagen diseases, are characterized by chronic inflammation. Mutual interrelationship between angiogenesis and chronic inflammation has already been demonstrated. The aim of the study was to examine the effect of sera from patients with systemic autoimmune diseases on angiogenesis induced by human mononuclear cells. The study population consisted of 43 patients with a systemic autoimmune disease associated with pulmonary manifestations, divided into three groups: 14 with Wegener's granulomatosis (WG), 13 with systemic sclerosis (SS), and 16 with collagen vascular diseases (CVD) such as rheumatoid arthritis, systemic lupus erythematosus, and dermatomyositis. The control group consisted of 15 healthy volunteers. Clinical status was evaluated using a questionnaire. Standard chest radiographs were performed in all patients. Pulmonary function tests were performed according to the ERS standards. An animal model of a leukocyte-induced angiogenesis assay was used as an angiogenic test. Sera from WG and CVD patients significantly stimulated angiogenesis compared with healthy subjects (P<0.001). On the other hand, sera from healthy donors exerted a proangiogenic effect compared with PBS. In contrast, sera from SS patients significantly (P<0.001) inhibited angiogenesis compared with sera from healthy subjects and PBS. Proangiogenic effect of sera from systemic diseases patients depended on radiological changes. No significant correlation between a degree of dyspnea or functional pulmonary tests and the number of new vessels or angiogenesis index was found. Sera from patients with systemic autoimmune diseases and healthy people constitute the source of mediators modulating angiogenesis. These modulatory effects differ depending on the disease entity.

Chronic crusting, nasal carriage of Staphylococcus aureus and relapse rate in pulmonary Wegener's granulomatosis.

Wegener's granulomatosis is a systemic disease characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract and necrotizing crescentic glomerulonephritis. Nasal carriage of S. aureus is considered a risk factor for S. aureus infections. The aim was to examine possible risk factors for relapse including refractory nasal carriage of Staphylococcus aureus in patients with Wegener's granulomatosis. Swab cultures from anterior nares for S. aureus were taken in consecutive patients (n=28), with limited (n=15) and systemic forms (n=13) of biopsy-proven Wegener's granulomatosis. The occurrence of infection and relapses were identified according to defined criteria. Seventeen of the 28 patients (60%: 95% Cl, 41-76%) were found to be chronic nasal carriers of S. aureus (> or =80% of nasal cultures positive for S. aureus). A hazard regression analysis identified chronic nasal carriage of S. aureus as independent risk factor for relapse (HR-4.56; Cl 2.45-7.65) in patients with limited Wegener's granulomatosis. Chronic nasal carriage of S. aureus characterized patients with Wegener's granulomatosis, who are more prone to relapses.

Association between clinical activity and high-resolution tomography findings in pulmonary Wegener's granulomacytosis.

Wegener's granulomatosis is characterized histologically by necrotizing granulomatous angitis that most commonly involves the upper, lower respiratory tract, and kidneys, but may affect any organ system. The aim of the study was to assess the usefulness of high-resolution computed tomography (HRCT) for evaluating pulmonary disease activity in Wegener's granulomatosis patients. Pulmonary disease activity at the time of examination was scored in 66 patients with Wegener's granulomatosis according to clinical, radiological, and bronchoscopic findings: activity group (n=43, Group 1), past activity group (n=14, Group 2). Of 66 staging examinations, 57 (86%) revealed abnormal CT scans: masses or nodules (30 patients in Group 1 and 6 patients in Group 2, parenchymal opacifications (15 in Group 1 and 1 in Group 2), pleural irregularity (3 in Group 1 and 10 in Group 2). We conclude that HRCT may be a useful supplement to clinical scoring of disease activity in Wegener's granulomatosis with pulmonary involvement.

Procalcitonin as an indicator of systemic response to infection in active pulmonary Wegener's granulomacytosis.

Differential diagnosis of infection during active immune disease, such as Wegener's granulomatosis (Wegener's granulomatosis), is a major clinical challenge. Laboratory measures, erythrocyte sedimentation rate or C-reactive protein, can be elevated in infections that supervene, or coinciding with, in active Wegener's granulomatosis, and thus are nonspecific. The aim of the study was to compare the serum levels of procalcitonin (PCT) in patients with active and inactive disease. Twenty two sera were tested from 10 patients with active, generalized, and biopsyproven Wegener's granulomatosis, with pulmonary involvement, and 12 patients with nonactive one. PCT levels were measured using an immunoluminometric assay. The PCT level was markedly elevated (1.2-3.6 ng/ml) in 9 of the 10 sera from active and 2 of the 12 sera from nonactive Wegener's granulomatosis. PCT levels were in the normal range (0.28-0.56 ng/ml) in the remaining patients with nonactive Wegener's granulomatosis. We conclude that serum procalcitonin levels may be a potentially useful marker in the diagnosis of bacterial infection supervening in active Wegener's granulomatosis.

Modulatory effect of sera from sarcoidosis patients on mononuclear cell-induced angiogenesis.

Sarcoidosis (SAR) is a systemic granulomatous inflammatory disease characterized by recruitment and activation of peripheral blood mononuclear cells to the sites of disease. Neovascularisation is a principal vascular response in chronic inflammation and hypoxia. The aim of the study was to evaluate the effect of sera from sarcoidosis patients on angiogenic capability of different subsets of normal peripheral human mononuclear cells (MNC) in relation to IL-6 and IL-8 serum levels, to radiological stages of disease and to the presence of extrapulmonary changes. Serum samples obtained from 42 sarcoidosis patients were examined. There were 12 patients in stage I, 16 patients in stage II, and 14 in stage III. In order to quantify angiogenesis, a leukocyte-induced angiogenesis assay was performed by a method of Sidky and Auerbach. MNC were depleted in monocytes by glass adherence and phagocytosis of iron particles techniques. IL-6 and IL-8 in sera from sarcoidosis patients were evaluated by an ELISA-based assay. Sera from sarcoidosis patients enhanced angiogenic capability of normal MNC significantly stronger than sera from healthy donors (P<0.001). Angiogenic activity of sera in sarcoidosis depended on the stage of disease and appeared most pronounced in stage II (P<0.05). Sera from patients with extrapulmonary changes exerted stronger effect on angiogenesis than sera from patients with thoracic changes only (P<0.001). IL-6 and IL-8 serum level correlated with each other, but no correlation was found between IL-6 and IL-8 serum level and angiogenic activity of the examined sera. Removal of monocytes from MNC eliminated the effect of sera from sarcoidosis patients on angiogenesis compared with the effect of these sera on intact MNC (P<0.001). Sera from sarcoidosis patients and from healthy people constitute a source of mediators participating in angiogenesis. Sera from sarcoidosis patients prime monocytes for production of proangiogenic factors.

TNFalpha and INFgamma inducing capacity of sera from patients with interstitial lung disease in relation to its angiogenesis activity.

Sera from interstitial lung diseases (ILD) constitute a source of mediators participating in angiogenesis. The nature of these mediators is unknown. The aim of our study was to asses whether preincubation with sera from ILD patients could influence TNFalpha and INFgamma production by normal mononuclear cells (MNC) challenged with LPS (for TNFalpha) or PHA (for INFgamma), and to correlate the cytokine levels with angiogenic properties of sera. The study population consisted of 53 patients with ILD, 16 with sarcoidosis (SAR), 11 with avian fanciers' lung (AFL), 10 with scleroderma with pulmonary manifestations (SCL), 9 with Wegener's granulomatosis (WG), and 7 with pulmonary Langerhans' cell histiocytosis (PLH). As a control, sera from 10 healthy volunteers were used. Neovascularization was measured by a leukocyte-induced angiogenesis assay according to Sidky and Auerbach. TNFalpha and INFgamma production was estimated by a one-step culture immunoassay CytoTraptrade mark TNFalpha DIA (Biosource Europe S.A.) after 3 h of incubation with LPS (TNFalpha) and 24 h incubation with PHA (INFgamma). Sera from sarcoidosis patients, WG patients, and AFL patients significantly stimulated angiogenesis in comparison with sera from healthy donors (P<0.001). Sera from PLH and SCL patients presented anti-angiogenic properties in comparison with sera from healthy donors and from each examined group (P<0.001). Comparing with other groups, preincubation with sera from AFL and WG patients led to a significant increase in TNFalpha production by normal MNC. Highly significant correlation between serum angiogenic activity and TNFalpha production by MNC was observed in SCL, WG, and AFL (r=0.74, P<0.01). we conclude that TNFalpha may play an important role in neovascularization in ILD.

The role ANCA and anti-GBM antibodies in pulmonary-renal syndrome due to Wegener's granulomatosis.

Pulmonary-renal syndrome (PRS) is defined as a diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis. We present a retrospective study of 22 consecutive patients with Wegener's granulomatosis (WG). Logistic regression analysis and a Wilcoxon test were included in the statistics. Survival time death risk were assessed using the Kaplan-Meier estimator and the Cox proportional hazard model. At recognition, the median Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) was 30.0 (23.0-32.5), PO2 on air was 5.8+/-0.5 kPa, creatinine level was 7.2+/-1.4 mg/dl. Fifteen patients were PR3 positive, among them 4 patients were also positive for anti-glomerular basement membrane antibodies (anti-GBM). Renal biopsy was performed in 16 patients. Histological examination reviled segmental necrotizing crescentic GN in 15 patients. Thirteen patients were initially dialysis-dependent, and 7 required ventilatory support. All patients were treated with methylprednisolone and cyclophosphamide (pulses). The patients were followed up for 24+/-8 months. Of the survivors, 55% and 31% were alive after 1 and 2 years. Early recognition and proper treatment may improve outcome in PRS.

Humoral immune response against 38-kDa and 16-kDa mycobacterial antigens in bone and joint tuberculosis.

SETTING: The diagnosis of bone and joint tuberculosis (BTB) is difficult, and diagnostic delays often occur. A reliable serological test detecting anti-mycobacterial antibodies would thus be of some use in this form of the disease. OBJECTIVE: To evaluate the diagnostic accuracy of an assay detecting IgG against 38-kDa and 16-kDa recombinant mycobacterial antigens in BTB. MATERIALS AND METHODS: In a prospective study, serum samples from 124 subjects were examined: 30 BTB cases, 40 non-specific bone and joint infection patients (NSBI), 30 lung cancer patients (LC), and 24 healthy volunteers (HC). An ELISA-based test (Pathozyme TB complex plus) was used. RESULTS: The cut-off level was established at 150 U/ml according to receiver operating characteristic (ROC) curves. The quantified level of sensitivity of the test detecting BTB was 56%, at a specificity of 99%. The positive and negative predictive values were respectively 94% and 88%. Mean IgG level in the BTB group was 470 +/- 761 U/ml (mean +/- SD), and was significantly higher than the antibody level in the control groups (NSBI 58 +/- 42 U/ml, LC 43 +/- 38 U/ml, HC 40 +/- 29 U/ml). CONCLUSION: The test presents an acceptable level of sensitivity and very good specificity in the diagnosis of BTB, and can be used in combination with other methods to increase diagnostic accuracy in this disease.