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1.
Clin Exp Rheumatol ; 30(3): 409-13, 2012.
Article in English | MEDLINE | ID: mdl-22513222

ABSTRACT

OBJECTIVES: To investigate the long-term effects of megadoses of intravenous immunoglobulin (IVIG) in a small cohort of patients with relapsing primary APS resistant to conventional treatments. METHODS: Five primary APS patients, 4 women, mean age 45.1 years (range 31-76 years), were considered eligible for IVIG therapy due to relapsing thrombotic events (4 recurrent venous thromboses, 2 ischaemic cerebral strokes, 2 pulmonary thromboembolisms, 1 thrombotic event on the vena cava filter), despite conventional therapy with anticoagulants. All patients had anti-nuclear antibodies at low-medium titre without other signs or symptoms of systemic lupus erythematosus. IVIG was combined with hydroxychloroquine and, in patients with cerebral strokes, acetylsalicylic acid. Three consecutive daily infusions of IVIG were administered intravenously at a dose of 0.4 g/kg/day every month for 3 months, followed by a single monthly infusion for 9 months. RESULTS: No further thromboses occurred in the 5 treated patients (mean follow-up 89.2 months, range 61-114). Visual analogue score (VAS 0-10) improved (mean 3.5, range 3.0-5.0, before, and 7.35, range 9.9-6.0, p= 0.05) after IVIG treatment. CONCLUSIONS: In a long-term (>5 years) open study in a small cohort of high risk primary APS patients, IVIG was found to be effective in preventing recurrent thrombosis. Full understanding of the mechanisms and efficacy, as well as the optimal doses of IVIG in APS patients with recurrent thrombosis, will require appropriately designed clinical studies. Presently, IVIG use is restricted by costs and limited availability.


Subject(s)
Anticoagulants/therapeutic use , Antiphospholipid Syndrome/drug therapy , Antiphospholipid Syndrome/immunology , Immunoglobulins, Intravenous/therapeutic use , Thrombosis/immunology , Thrombosis/prevention & control , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antirheumatic Agents/therapeutic use , Aspirin/therapeutic use , Drug Resistance/immunology , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/therapeutic use , Intracranial Thrombosis/immunology , Intracranial Thrombosis/prevention & control , Male , Middle Aged , Pulmonary Embolism/immunology , Pulmonary Embolism/prevention & control , Secondary Prevention , Stroke/immunology , Stroke/prevention & control , Venous Thrombosis/immunology , Venous Thrombosis/prevention & control
3.
Clin Exp Rheumatol ; 26(3 Suppl 49): S67-71, 2008.
Article in English | MEDLINE | ID: mdl-18799057

ABSTRACT

BACKGROUND: Cyclophosphamide (CYC) is thought to be the most effective treatment for antineutrophil cytoplasmatic antibody (ANCA)-associated idiopathic systemic vasculitis with severe organ or life threatening presentation. The key mechanism of action of CYC is suppression of the B lymphocyte activity. However, a considerable minority of patients either remains refractory to conventional therapy or experiences dose-limiting side effects. METHODS: In the present study, rituximab (4 weekly doses of 375 mg/m2 and 2 more doses at 1-month interval) was intravenously administered as a rescue therapy to 7 patients (4 affected by idiopathic systemic microscopic polyangiitis, 2 by Wegener's granulomatosis, and 1 affected by Churg Strauss syndrome). The study group was made up of 3 women and 4 men, mean age 61.5 years (39-71), intolerant or refractory to more conventional therapy. Four patients had histologically confirmed paucimmune necrotizing glomerulonephritis. RESULTS: Significant decreases were observed in levels of serum creatinine, proteinuria, erythrocyte sedimentation rate, C-reactive protein, and ANCA titers within the first 12 months of follow-up. Arthralgia and weakness rapidly disappeared in all patients. Four out of five patients reported a decrease in the degree of paresthesia, paralleled by an improvement in the electrodiagnostic parameters. A significant improvement was observed in both Birmingham Vasculitis Activity Score and Vasculitis Damage Index. Side effects were negligible. CONCLUSION: In this sample of patients with idiopathic systemic vasculitis that was refractory or intolerant to conventional treatment, rituximab was found to be a safe and effective rescue therapy.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Churg-Strauss Syndrome/drug therapy , Granulomatosis with Polyangiitis/drug therapy , Immunologic Factors/therapeutic use , Adult , Aged , Antibodies, Antineutrophil Cytoplasmic/immunology , Antibodies, Monoclonal, Murine-Derived , Autoantibodies , Churg-Strauss Syndrome/immunology , Cohort Studies , Drug Resistance , Female , Granulomatosis with Polyangiitis/immunology , Humans , Male , Middle Aged , Rituximab , Treatment Outcome
4.
Clin Exp Rheumatol ; 25(4): 556-62, 2007.
Article in English | MEDLINE | ID: mdl-17888211

ABSTRACT

OBJECTIVES: Over the last two decades, increasing interest has been focused on the association between autoimmune polyneuropathies and anti-neuronal autoantibodies in immune-mediated polyneuropathy. The possible appearance of these autoantibodies in systemic diseases that are not limited to the nervous system has not been fully addressed yet. METHODS: We evaluated 32 patients with systemic lupus erythematosus, 34 patients with hepatitis C virus-associated mixed IgM-k/IgG cryoglobulinemia, 19 with small vessel ANCA-associated vasculitis, and 20 patients with Sjögren's syndrome by means of an immunoenzyme method of anti-neuronal autoantibody detection. RESULTS: As compared to normals, a significant increase (p < 0.001) in plasma titers of both IgM and IgG anti-GM1 ganglioside and IgM and IgG anti-sulfatide was observed in patients with systemic lupus erythematosus, mixed cryoglobulinemia and Sjög-ren's syndrome. Idiopathic systemic vasculitis patients were found to have significantly increased levels of anti-sulfatide IgG autoantibodies (p < 0.001). Clinical and electrophysiologic studies revealed that abnormal titers of anti-neuronal antibodies were associated with evidence of neuropathy in patients with systemic lupus erythematosus and ANCA-related vasculitis (p < 0.05) as well as in patients with mixed cryoglobulinemia and Sjögren's syndrome (p < 0.001). CONCLUSION: Anti-GM1 and anti-sulfatide antibodies are frequently found in patients with small vessel ANCA-associated vasculitis and other multi-organ immune-mediated diseases. Upon detection of these antibodies, accurate neurologic examination should be carried out due to the significant association that can be found between these serologic abnormalities and the involvement of the peripheral nervous system as also detected by electrophysiologic studies. This study supports the unexpected possibility that anti-neuronal reactivity may be a direct trigger of neurologic injury in these systemic disorders.


Subject(s)
Autoantibodies/blood , Cryoglobulinemia/immunology , Gangliosidosis, GM1/immunology , Lupus Erythematosus, Systemic/immunology , Sjogren's Syndrome/immunology , Sulfoglycosphingolipids/immunology , Vasculitis/immunology , Adult , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged
5.
G Ital Nefrol ; 24(2): 111-20, 2007.
Article in Italian | MEDLINE | ID: mdl-17458826

ABSTRACT

The diagnosis of antiphospholipid syndrome (APS) relies on clinical and laboratory criteria, which have been recently outlined in specific consensus conferences. Renal involvement in APS is not infrequent and includes different clinical patterns. For clinical purposes a distinction can be made between large vessel and microvascular involvement. Renal artery stenosis is frequent in APS. In case of microvascular involvement with an acute clinical course a differential diagnosis with other thrombotic microangiopathic diseases has to be made, taking in account thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, malignant hypertension, drug nephrotoxicity (cyclosporin) and others. The disease is often chronic, with hypertension, different degrees of renal insufficiency and mild proteinuria. In patients with systemic lupus erythematosus and antiphospholipid antibodies the prognosis of kidney disease is generally poorer than in lupus alone. Finally, the kidney is almost invariably a target in catastrophic antiphospholipid syndrome. Anticoagulation is the therapy of choice, especially in arterial stenosis and acute disease, but is probably also indicated in chronic and subacute patterns. The role of immunomodulatory therapy has to be assessed.


Subject(s)
Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/complications , Immunologic Factors/blood , Kidney Diseases/immunology , Anticoagulants/therapeutic use , Antiphospholipid Syndrome/immunology , Diagnosis, Differential , Drug Therapy, Combination , Humans , Hypertension/immunology , Immunosuppressive Agents/therapeutic use , Kidney Diseases/diagnosis , Kidney Diseases/drug therapy , Renal Artery Obstruction/immunology
6.
Clin Exp Immunol ; 139(2): 225-35, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15654821

ABSTRACT

The response of mesangial cells to a phlogistic challenge includes cell proliferation and mesangial matrix expansion. Cell proliferation is a highly regulated process which includes enhancing factors such as cyclins, cyclin dependent kinases, and inhibitory proteins, such as p27(kip1). The aim of the study was to evaluate the effects of Mycophenolate mofetil (MMF), and roscovitine (R), on the cell cycle regulatory system when administered in the florid phase of the experimental model of mesangial proliferative nephritis induced by the anti Thy-1 antigen monoclonal antibody. Three days after nephritis induction, different groups were given MMF and R. Rats treated with MMF or R showed a slight decrease in mesangial proliferation and matrix expansion. Samples of cortical tissue were tested by 'real time' RT-PCR in order to study gene expression of cyclins B, D1, D2, D3, E, and the cyclin inhibitor p27(kip1). Localization of mRNA was evaluated by in situ hybridization. Real time RT-PCR analysis showed a significant decrease in cyclins B, D1, D2, and D3 in rats treated with either MMF or R as compared to controls. Both MMF and R treatment induced a significant increase in p27(kip1) mRNA expression. In situ hybridization showed a mesangial-endothelial expression pattern in glomeruli. The number of labelled cells per glomerulus, the number of positive glomeruli in each examined slide as well as cyclin D2 and D3 signal intensity was significantly lower in rats treated with MMF or R as compared to controls, whereas MMF or R treatment up-regulated p27(kip1) mRNA expression. Immunohistochemical evaluation of p27(kip1) aimed to examine the influence of MMF or R on protein expression confirmed up-regulation.


Subject(s)
Cell Cycle Proteins/metabolism , Cyclins/metabolism , Glomerulonephritis, Membranoproliferative/drug therapy , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Purines/therapeutic use , Tumor Suppressor Proteins/metabolism , Animals , Cell Cycle Proteins/genetics , Cyclin B/genetics , Cyclin B/metabolism , Cyclin D , Cyclin-Dependent Kinase Inhibitor p27 , Cyclins/genetics , Glomerular Mesangium/immunology , Glomerular Mesangium/metabolism , Glomerulonephritis, Membranoproliferative/immunology , Glomerulonephritis, Membranoproliferative/metabolism , Immunohistochemistry/methods , In Situ Hybridization/methods , Male , Models, Animal , RNA, Messenger/analysis , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Roscovitine , Th1 Cells/immunology , Tumor Suppressor Proteins/genetics
8.
Environ Res ; 81(1): 62-71, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10361027

ABSTRACT

Human exposure to ethylene oxide (EtO) occurs mainly through inhalation of occupational polluted air and tobacco smoke. EtO is able to react with DNA and proteins producing some molecular adducts. One of these, resulting from reaction between EtO and valine in hemoglobin, is N-(2-hydroxyethyl) valine (HOEtVal). This adduct represents a biological effective dose marker, the level of which correlates linearly with the alkylating activity occurring in DNA. The aim of the present study was to measure HOEtVal in 146 urbanized adult and healthy subjects, nonoccupationally exposed to EtO, and to correlate it with smoke habits. HOEtVal showed a direct positive relationship to tobacco smoke exposure quantified by questionnaire, urinary cotinine (r=0.64509), and the number of cigarettes (r=0. 6308) actively or passively smoked. Results relative to HOEtVal and urinary cotinine in adults distinguish well between active and passive smokers but do not allow distinguishment between passive smokers and nonsmokers. Nevertheless, several authors demonstrated a very good capacity of cotinine to discriminate inside groups of adolescents passive smokers. Therefore, the future objective of the present study is a closer inspection of the two biomarkers with respect to passive exposure to tobacco smoke considering a large group of adolescents. Finally, the correlation between urinary cotinine and HOEtVal increases knowledge about early steps of the carcinogenic process due to active exposure to tobacco smoke.


Subject(s)
Ethylene Oxide/analysis , Tobacco Smoke Pollution/analysis , Valine/analogs & derivatives , Adolescent , Adult , Biomarkers/blood , Biomarkers/urine , Carcinogens/analysis , Cotinine/urine , Ethylene Oxide/blood , Female , Gas Chromatography-Mass Spectrometry/methods , Hemoglobins/analysis , Humans , Male , Risk Factors , Smoking/blood , Smoking/urine , Surveys and Questionnaires , Urban Population , Valine/blood
10.
Ren Fail ; 17(5): 565-73, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8570869

ABSTRACT

The aim of this study was the detection of HCV viremia in both anti-HCV antibody positive and negative hemodialysis patients. Sera from 75 patients on extracorporeal blood purification in the same dialysis unit were analyzed. Anti-HCV antibodies were detected using a 2nd-generation ELISA assay and in all positive cases a RIBA 3rd-generation test was performed. HCV-RNA was tested by a reverse transcription-nested polymerase chain reaction (RT-PCR) assay with primers located in the 5' region. PCR products were analyzed by a nonradioactive hybridation assay. The presence of anti-HCV antibodies was detected in 30 (40%) patients by means of ELISA II test; 28 of them were RIBA III positive and two indeterminate. Twenty-four of the 30 HCV Ab ELISA II positive patients (80%) were HCV-RNA positive (23 RIBA III positive and 1 indeterminate). Six anti-HCV Ab ELISA II positive patients tested negative for HCV-RNA (20%); 5 of these patients were also positive for anti-HCV antibodies with a RIBA III test and 1 was indeterminate. None of the anti-HCV negative patients was HCR-RNA positive. In two cases we documented the disappearance of viremia after an acute HCV infection, with the persistence of antibody reactivity. In conclusion, anti-HCV antibody positive hemodialysis patients should be considered as potentially infectious.


Subject(s)
Hepacivirus/isolation & purification , Hepatitis C Antibodies/blood , Hepatitis C/diagnosis , Renal Dialysis , Viremia/diagnosis , Adult , Aged , Aged, 80 and over , Base Sequence , DNA, Viral/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Molecular Sequence Data , Polymerase Chain Reaction , Retrospective Studies , Transcription, Genetic
13.
Kidney Int ; 35(2): 622-31, 1989 Feb.
Article in English | MEDLINE | ID: mdl-2709668

ABSTRACT

The functional effects directly induced by dialysis membranes on peripheral monocytes were analyzed in a plasma-free model of simulated dialysis using Cuprophan, cuprammonium rayon, polyacrylonitrile, polymethylmetacrilate and polysulphone membranes. A severe reduction of monocyte phagocytosis of IgG-coated erythrocytes was found by using Cuprophan and cuproammonium rayon. The cytofluorimetric analysis of several cell surface receptors, involved in the immune phagocytosis and recognizable by five quoted monoclonal antibodies, did not reveal any significant change. The defective phagocytosis of the IgG-coated erythrocytes by monocytes, due to the exposure to cellulose-derived membranes, was paralleled by an impaired interiorization of heat-aggregated human immunoglobulins, as analyzed by electron microscopy. The cell membrane binding of aggregated immunoglobulins was found to be unaffected. The defect was associated to a remarkably depressed generation of reactive oxygen species after Zymosan stimulation. Therefore, the defective immune phagocytosis induced by exposure of monocytes to cellulosic membranes was not due to a receptor rearrangement or an impaired binding of ingestible particles, but to a reduced internalization capacity probably related to an energy source exhaustion (as shown by the lack of response to stimuli able to induce oxidizing species production). These features are similar to those described in monocytes from acute systemic lupus erythematosus patients.


Subject(s)
Kidneys, Artificial , Leukocytes, Mononuclear/physiology , Membranes, Artificial , Cell Survival , Humans , Microscopy, Electron , Phagocytosis , Receptors, Fc/physiology
14.
Eur J Epidemiol ; 4(1): 119-20, 1988 Mar.
Article in English | MEDLINE | ID: mdl-3162716

ABSTRACT

We report here the history of the first case of occupationally acquired HIV infection in Italy. Results of serological investigations sequentially performed allow the investigators to outline the natural history of the infection in this case.


Subject(s)
Acquired Immunodeficiency Syndrome/etiology , Nurses , Occupational Diseases/etiology , Acquired Immunodeficiency Syndrome/immunology , Adult , Antigens, Viral/analysis , Female , HIV/immunology , HIV Antigens , HIV Seropositivity/complications , Humans , Italy , Occupational Diseases/immunology , Risk Factors
15.
Artif Organs ; 9(4): 351-60, 1985 Nov.
Article in English | MEDLINE | ID: mdl-3878699

ABSTRACT

Plasma exchange (PE) has recently been proposed for primary immunoglobulin (Ig)-A nephropathy (PIgAGN) with progressive course. To develop suitable guidelines for PE in these cases, the authors evaluated the clinical usefulness of some immunological parameters in five patients with PIgAGN treated with PE combined with immunosuppressive drugs and small doses of corticosteroids. These parameters included the levels of IgA-containing immune complexes (IgAIC) by a specific conglutinin assay, the function of the mononuclear phagocyte system (MPS) by the in vivo clearance of IgG-sensitized erythrocytes, and complement activation as determined by C3d measurement. HLA types were also determined. Three patients had an acute nephritic syndrome with a rapidly progressive course, one of them showing sclerotic histologic changes. The two other cases had a relentless progression toward renal failure. In the patient with sclerotic PIgAGN, the MPS function was normal and the IgAIC and C3d levels were low throughout the treatment. In the other four cases, the high IgAIC and C3d levels and the MPS dysfunction found before treatment markedly improved after several PEs. The immunological parameters remained normal during the post-PE follow-up in two cases with acute nephritic syndrome and rapidly progressive course, but worsened again in two cases with a relentless course, particularly in one who possessed the B8/DR3 HLA type. Immunological monitoring including IgAIC, C3d, and MPS function is proposed, in addition to histological and clinical evaluation, as a guideline for PE in PIgAGN with evolving course.


Subject(s)
Glomerulonephritis, IGA/therapy , Plasma Exchange , Adolescent , Antigen-Antibody Complex/metabolism , Complement C3/metabolism , Complement C3d , Female , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/immunology , HLA Antigens , Humans , Immunoglobulin A/metabolism , Male , Middle Aged , Nephrotic Syndrome/complications , Nephrotic Syndrome/immunology , Nephrotic Syndrome/therapy , Phagocytes/immunology , Time Factors
16.
Int J Artif Organs ; 8 Suppl 2: 55-8, 1985 Jul.
Article in English | MEDLINE | ID: mdl-4055114

ABSTRACT

Five patients with progressive primary IgA nephropathy (PIgAGN) were treated by plasma-exchange (PE) combined with immunosuppressive drugs. Circulating IgA-containing immune complexes (IgAIC), detected by a specific conglutinin solid phase assay, were monitored. Two patients with acute nephritic syndrome and rapidly progressing course, crescent formations and high levels of IgAIC had substantial lasting clinical improvement after several PE, with a fall in IgAIC levels. Another rapidly progressive case with marked sclerotic changes and a longer history of nephritic syndrome, but with normal levels of IgAIC, did not show any clinical improvement after PE. Two patients with a PIgAGN diagnosed several years before and presenting slowly evolutive course had no substantial clinical benefit from PE treatment. IgAIC levels, very high before PE temporarily decreased, but returned to the previous values after the end of the treatment. We conclude that PE combined with immunosuppressive treatment may be of clinical benefit for cases with acute nephritic syndrome of recent onset who still have high levels of IgAIC, even when important crescent formations are present.


Subject(s)
Autoimmune Diseases/therapy , Kidney Diseases/therapy , Plasma Exchange , Adolescent , Adult , Child , Female , Humans , Immunoglobulin A/analysis , Kidney Diseases/immunology , Male , Middle Aged
17.
Nephron ; 40(4): 488-90, 1985.
Article in English | MEDLINE | ID: mdl-4022221

ABSTRACT

Primary IgA nephropathy is generally considered a benign disease, but progression to renal failure is not uncommon and a rapidly progressive course is observed in some cases, especially when extensive epithelial crescents are present. Circulating IgA-containing immune complexes (IgAIC) seem to play the most important pathogenetical role, hence the authors adopted plasmapheretic treatment in association with immunosuppressive drugs for 1 patient affected by primary IgA nephritis, with florid crescents and progressive renal failure. IgAIC decreased significantly after each plasma exchange and finally returned to normal values; over the same period urinary protein loss and heavy microscopic hematuria gradually disappeared and renal function was completely recovered.


Subject(s)
Antigen-Antibody Complex/analysis , Glomerulonephritis, IGA/therapy , Plasmapheresis , Glomerulonephritis, IGA/immunology , Humans , Male , Middle Aged
19.
Respiration ; 44(2): 90-6, 1983.
Article in English | MEDLINE | ID: mdl-6836194

ABSTRACT

Static and dynamic lung volumes, flow-volume curve in air and after He-O2 were carried out in 5 normal subjects baseline, immediately after rapid infusion of 2 litres of normal saline, and then 15, 30 and 60 min after. At the end of the infusion, a marked reduction of delta MEF50, FVC, FEV1, MEF50, MEF25 and an increase of Viso V and CV/VC were observed in all the subjects. The poor response to He-O2 suggests a predominant increase of small airway resistance after rapid infusion. In the recovery phase, He-O2 tests promptly returned to control values, while an increased CV/VC was detectable until 30 min after the infusion.


Subject(s)
Airway Obstruction/pathology , Sodium Chloride/administration & dosage , Adult , Airway Obstruction/chemically induced , Arteries , Closing Volume , Forced Expiratory Flow Rates , Humans , Infusions, Parenteral , Male , Maximal Expiratory Flow Rate , Oxygen/blood , Partial Pressure , Vital Capacity
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