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Biomedical subjects

M Cuchacovich

Publications and source records attributed to M Cuchacovich.

At least 19 recordsLinked to original sources
PubMed2004

Tumour necrosis factor-alpha (TNF-alpha) levels and influence of -308 TNF-alpha promoter polymorphism on the responsiveness to infliximab in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the influence of -308 tumour necrosis factor-alpha (TNF-alpha) promoter polymorphism and circulating TNF-alpha levels in the clinical response to the infliximab treatment in patients with rheumatoid arthritis (RA). METHODS: One hundred and thirty-two RA patients were genotyped for TNF-alpha promoter by polymerase-chain reaction restriction fragment-length polymorphism (PCR-RFLP) analysis. Ten patients with the -308 TNF-alpha gene promoter genotype G/A, and 10 with the G/G genotype were selected and received 3 mg/kg of infliximab at Weeks 0, 2, 6, and 14. RESULTS: Both groups showed a significant improvement with treatment in all variables studied. Total mean TNF-alpha levels increased significantly with respect to basal levels in most of patients after treatment [probability (p)=0.04]. Only patients from G/A showed a statistically significant correlation between ACR 50 and the increase of TNF-alpha levels (p<0.03). CONCLUSION: A relationship was detected between ACR criteria of improvement and increased circulating TNF-alpha levels in RA patients subjected to anti-TNF-alpha therapy.

Adult↗
PubMed2003

The -308 polymorphism in the tumour necrosis factor (TNF) gene promoter region and ex vivo lipopolysaccharide-induced TNF expression and cytotoxic activity in Chilean patients with rheumatoid arthritis.

OBJECTIVE: To investigate the association of the -308 polymorphism in the promoter region of the tumour necrosis factor (TNF) gene with susceptibility to the development of RA. We also explored the expression and cytotoxicity of TNF in relation to the -308 polymorphism. METHODS: We recruited 92 RA patients and 42 healthy control subjects. Genotyping for the TNF promoter was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. To study the overexpression of TNF we used a whole-blood culture system. TNF cytotoxicity was assessed in the L929 cell line. RESULTS: The TNF2 allele was found in 23% of RA patients and 10% of controls. Although both groups showed high variability in serum TNF concentration, in the lipopolysaccharide-induced TNF level and in the cytotoxicity of the cytokine in the L929 cell line, these differences were not associated with the -308 TNF polymorphism. CONCLUSION: No associations were found between the -308 TNF promoter polymorphism, serum and ex vivo TNF levels and the cytotoxic activity of TNF in RA patients.

Adult↗
PubMed2000

[Renal scleroderma crisis. Role of scleroderma vasculopathy in the induction of cutaneous and visceral fibrosis in 2 cases].

Although fibrosis and vasculopathy coexist in most patients with progressive systemic sclerosis, it is not clear if these events are the result of an unique etiologic factor or if one is consequence of the other. We report two cases of progressive systemic sclerosis that evolved to a renal scleroderma crisis. A 36 years old female presented with a Sjögren syndrome and painful subcutaneous nodules whose biopsy showed perivascular lymphocytic infiltration, perivascular thickening and normal skin. The ESR was 100 mm/h. She developed an hypertensive crisis and progressive renal failure, followed by a rapidly evolving progressive systemic sclerosis. The patient died in the course of this crisis. A 32 years old female with a progressive systemic sclerosis refractory to D-penicillamine treatment, receiving cyclosporin, presented a renal scleroderma crisis, that was successfully treated, with complete recovery of renal function. We highlight the different evolution of these cases, probably due to an early diagnosis and a better experience in the management of this condition.

Acute Kidney Injury↗
PubMed2000

[Prognostic value of Sharp's index in the clinical and laboratory response to an intravenous methylprednisolone pulse in patients with rheumatoid arthritis].

BACKGROUND: No reliable variables to predict clinical or laboratory response to treatment in patients with rheumatoid arthritis were available until recently. AIM: To asses the potential predictive value of the Sharp's modified radiographic joint damage index for the assessment of clinical and laboratory response to a methylprednisolone i.v. pulse. PATIENTS AND METHODS: Twenty-two patients suffering from rheumatoid arthritis received a single i.v. pulse of 1 g of methylprednisolone. Hand X-rays were taken at baseline and blindly scored by two trained radiologists. Clinical and laboratory variables were assessed at baseline and at weekly intervals up to 30 days plus a 60 days final evaluation. Improvement was defined as a 50% amelioration in 4 variables. RESULTS: Assessment of radiographic scores had a high correlation between and within observers (intraclass correlation = 0.998). Sharp score did not reach statistical significance as global predictor for the inflammatory variable response to methylprednisolone. However, when the number of swollen joints was taken into account, patients with a low erosive score (Sharp < or = 50) had a more prolonged clinical response, than patients with higher erosive score (Sharp > 50) (Fisher test p = 0.023). It is of clinical importance to point out that among patients with high Sharp score there were also responders who reached a high level of improvement. A statistically significant correlation between the basal PCR serum titers and the radiographic score (p < 0.02) was observed. CONCLUSIONS: The number of swollen joints and other variables that consider joint structural changes should be considered for the assessment of rheumatoid arthritis patients.

Adolescent↗
PubMed1999

[Treatment of non infectious ocular inflammatory disease with low doses of cyclosporin A].

BACKGROUND: Cyclosporin A has an adequate immunosuppressive capacity and can be useful in the treatment of non infectious ocular inflammatory diseases. AIM: To describe the clinical effect of cyclosporin A treatment in low doses, along with corticosteroids, in the treatment of refractory ocular inflammatory diseases. PATIENTS AND METHODS: Twenty patients (13 female), aged 17 to 74 years old with severe and refractory ocular inflammatory diseases were studied. All except one, received variable doses of prednisone (10 to 60 mg/kg/day) and all received cyclosporin in doses that started in 2.5 mg/day and were increased to 5 mg/kg/day, according to clinical response. Patients were followed from 8 to 24 months, with monthly assessments of ocular inflammation (using a four point score), visual acuity and adverse effects of treatment. RESULTS: A two points or more reduction in the ocular inflammation score was observed in 52% of patients. Visual acuity improved in 10 subjects, stabilized in 8 and worsened in 2. Prednisone doses were reduced in most patients. Observed adverse effects were hypertension in 2 patients, creatinine elevation in 2, gastrointestinal disturbances in 3 and hypertrichosis in 12. A reduction of cyclosporin dose was required in these cases, but it was discontinued only in one patient with a vascular purpura. CONCLUSIONS: Low cyclosporin doses, associated to prednisone, are useful to reduce inflammation and improve visual acuity in patients with non infectious ocular inflammatory diseases, refractory to other treatment methods.

Adolescent↗
PubMed1998

Neonatal lupus syndrome: a case with chondrodysplasia punctata and other unusual manifestations.

We report a case of a newborn infant whose mother had systemic lupus erythematosus (SLE) diagnosed before pregnancy. The child had clinical manifestations of neonatal lupus as well as chondrodysplasia punctata and other findings that resemble the congenital anomalies associated with the use of oral anticoagulants, with no history of exposure. We speculate that the combined action of the different maternal autoantibodies may produce the whole spectrum of manifestations.

Abnormalities, Multiple↗
PubMed1998

[Comparison of the efficacy of intraarticular and intraarterial injections of two betamethasone preparations in patients with osteoarthritis or epicondilytis].

BACKGROUND: Local infiltration with corticoids is a simple therapy for rheumatic disorders devoid of systemic adverse reactions. AIM: To compare the efficacy of two betametasone preparations from two different pharmaceutical laboratories in the treatment of patients with osteoarthritis or epicondylitis. PATIENTS AND METHODS: Fourty patients with knee osteoarthritis and 12 patients with epicondylitis were studied. Using a double blind protocol, one of the two betametasone preparations was used for local infiltration of the lesions. The change in a global score of clinical variables including pain and disability was assessed after 30 days of the infiltration. RESULTS: In patients with osteoarthritis, the global score decreased significantly with both preparations, but no differences were observed between preparations (7.3 +/- 1.8 to 3.9 +/- 2.3 with preparation A and 7.8 +/- 1.9 to 3.6 +/- 2.3 with preparation B). In patients with epicondylitis, pain was also significantly reduced but no differences between preparations was observed (7 +/- 2.1 to 1.4 +/- 2.5 for preparation A and 4.6 +/- 2.8 to 1.2 +/- 1.6 for preparation B). CONCLUSIONS: Local infiltration with both betametasone preparations was equally effective in the treatment of patients with knee osteoarthritis or epicondilytis.

Adolescent↗
PubMed1996

Analysis of autoantibodies to plasminogen in the serum of patients with rheumatoid arthritis.

Sera from patients with rheumatoid arthritis containing high titers of anti-streptokinase antibodies were found to contain anti-plasminogen antibodies of the IgG and IgA classes. High titers of anti-plasminogen autoantibodies of the IgA class were also found in sera from patients with systemic lupus erythematosus and Sjögren syndrome. Studies of the immune response to thrombolytic therapy with streptokinase in patients with no prior history of autoimmune disease suggest a strong correlation between streptokinase administration and the appearance of autoantibodies to plasminogen of the IgA class. The IgA anti-plasminogen autoantibody is specific for an epitope in a region of plasminogen which binds streptokinase and the IgG autoantibody reacts with an epitope in the C-terminal region corresponding to the catalytic domain of the plasminogen zymogen. Our findings suggest a different origin for the two classes of anti-plasminogen immunoglobulins in rheumatoid arthritis patients. Since plasminogen binding to rheumatoid synovial fibroblasts is enhanced, the high titers of both classes of anti-plasminogen autoantibodies may add to the localization and perpetuation of the immune response. We suggest that plasminogen may be a target of the immune response in autoimmune disease.

Aminocaproic Acid↗
PubMed1996

Potential pathogenicity of deglycosylated IgG cross reactive with streptokinase and fibronectin in the serum of patients with rheumatoid arthritis.

OBJECTIVE: Fibronectin (FN) and the streptococcal plasminogen activator streptokinase (SK) share the epitope LTSRPA. This epitope is not reactive in native FN and it reacts with anti-SK antibodies only after plasmin digestion of the protein. To investigate a potential correlation between the high levels of anti-LTSRPA antibodies in sera of patients with rheumatoid arthritis (RA) and the perpetuation of the immune response characteristic of this disease, we analyzed their capacity to activate complement and the process of binding to the serum lectin mannan binding protein (MBP). METHODS: We used a radioimmunoassay to evaluate immune complexes between anti-LTSRPA IgG and FN, plasmin degraded FN, or the LTSRPA peptide for their capacity to activate complement C5 to C5a. Purified human serum lectin MBP was used to quantify the degree of exposed mannose or N-acetylglucosamine residues in the Fc region of anti-LTSRPA IgG of patients with RA and healthy controls. RESULTS: Anti-LTSRPA IgG from patients with RA have a greater capacity to activate complement C5 to C5a when bound to either the LTSRPA peptide or plasmin degraded FN in vitro. We found a very strong correlation between the complement activating capacity of the RA immune complexes and their binding to MBP. CONCLUSION: The enhanced capacity of RA anti-LTSRPA IgG immune complexes to activate complement C5 to C5a is directly correlated with their binding capacity to MBP. As MBP binding depends on exposed mannose or N-acetylglucosamine residues in the Fc region of the IgG molecule, these studies suggest that defective glycosylation of circulating anti-SK IgG may play a role in the etiology of RA.

Adult↗
PubMed1996

Antimitochondrial antibody detection by indirect immunofluorescence on mouse sperms.

Antimitochondrial antibodies (AMA) are characteristically present in the serum of patients with primary biliary cirrhosis (PBC). AMA detection constitutes an important step for the clinical diagnosis of PBC, the indirect immunofluorescence against cryostat sections of rat of mouse organs being the most common method used. This study presents an alternative method for AMA detection by indirect immunofluorescence using mouse sperms as substrate. Sera of 17 patients with PBC were examined for AMA using mouse sperms and frozen sections of rat kidney. With mouse sperms as substrate, all PBC sera were found to be AMA positive showing an intense fluorescent reaction on the mitochondrial sheath of mouse sperms (100% sensitivity). No false positive results were obtained with normal sera. Sera of 22 patients with collagen diseases (systemic lupus erithematosus and progressive systemic sclerosis) having defined reactivity to antigens other than mitochondrial antigens were also examined for AMA with both substrates; 19 of them resulted AMA negative. AMA diagnosis on mouse sperm substrate was found to be more sensitive than conventional rat kidney substrate. In addition, it has the advantage that it facilitates for the observer the visualization and reading of the fluorescent reaction on the mitochondria, due to the particular distribution of them on mouse sperms.

Animals↗
PubMed1996

[Patients with rheumatoid arthritis: study of the correlation between density of glucocorticoid receptors in synovial cells and clinical response to steroidal treatment].

BACKGROUND: The target cellular response to glucocorticoids is proportional to the concentrations or affinity of specific receptors to these substances. AIM: To look for a correlation between glucocorticoid receptor concentrations in synovial wall cells and the clinical response to steroidal treatment in patients with rheumatoid arthritis. PATIENTS AND METHODS: Twenty eight patients with rheumatoid arthritis were studied. Each subject was subjected to a synovial biopsy, in which a dry radioautographic technique for diffusible compounds was used. Patients were treated afterwards with three 500 mg intravenous pulses of methilprednisolone. RESULTS: A mean of 44.8% of synovial cells (range 30.1-62.8%) had binding sites for 3H dexamethasone. All patients had a significant clinical improvement after methylprednisolone. Multiple regression analysis did not show a correlation between clinical response and glucocorticoid receptor concentration. CONCLUSIONS: The lack of association between glucocorticoid receptor concentrations and clinical response could be due to the large steroid dose used, that saturated all available receptors.

Adolescent↗
PubMed1995

[Regional transient osteoporosis and reflex sympathetic dystrophy. Are they different entities or clinical variants of the same disease?].

We report a 50 years old male that evolved with alternating episodes of osteoporosis with pain, edema and erythema of both feet. The patient presented clinical and radiological evidences of both transient regional osteoporosis and reflex sympathetic dystrophy. The clinical evolution was documented with magnetic resonance imaging. The hypothesis that both entities could be different expressions of same syndrome is discussed.

Diagnosis, Differential↗
PubMed1995

[Treatment of ocular inflammatory disease with glucocorticoids and cyclophosphamide pulses].

UNLABELLED: The effectiveness, toxicity and prognostic factors influencing responses to cyclophosphamide (CP) iv pulses plus oral glucocorticosteroids (GC) in patients with GC-resistant ocular inflammatory diseases (OID) was evaluated in a cohort of 15 consecutive patients suffering from active, non-infectious OID refractory to oral GC. All patients underwent monthly evaluations with clinical, hematological, hepatic, renal and ophthalmologic tests. These included checking visual acuity and both anterior chamber and posterior segment inflammation. The overall effect evaluated by repeated measurements ANOVA demonstrated that after an average of 5 CP pulses 1-10, the group showed significant improvement regarding of visual acuity and inflammation (p < 0.000001). Amelioration was not sustained over time in patients with granulomatous uveitis. Patients with retinal vasculitis experienced rapid and sustained recovery. By the end of the follow-up period, 53% of the patients had improved, 20% remained stationary and 26% suffered visual acuity deterioration as compared with the baseline. No serious side effects were detected during treatment and follow-up. CONCLUSIONS: A combination of oral GC and iv CP pulses appears to be an effective way to treat patients suffering from noninfectious, non-granulomatous, GC-resistant OID.

Adult↗
PubMed1993

[Role of sex hormones in autoimmune diseases].

There is increasing body of evidence to suggest that sex hormones may be closely involved in the pathogenesis of autoimmune diseases in humans. In the present article we discuss heteroimmune response differences between males and females and the roles of gender and sex hormones in autoimmune diseases in various species. The general conclusions are the following. Androgens and perhaps progestogens may protect from autoimmune disease; however oestrogens seems to have a dualistic effect on the immune system. Is has been demonstrated that oestrogens suppress antigen-specific T-cell dependent immune reactions while enhance B-cell activities.

Animals↗
PubMed1992

Precision of the Larsen and the Sharp methods of assessing radiologic change in patients with rheumatoid arthritis.

OBJECTIVE: To compare the sensitivity of Sharp's and Larsen's radiographic scoring methods for detecting change in rheumatoid arthritis (RA) over time. METHODS: Radiographs of the hands and wrists were taken at the beginning and at the end of a 2-year followup period, in 42 patients with active RA. Films were scored blindly using both scoring methods. Patients were under treatment with methotrexate (intramuscular injections). RESULTS: Radiographic evidence of progression or amelioration was detected in 25 patients by Larsen's method and in 35 patients by Sharp's method. The relative sensitivity to change over time was greater for Sharp's method (0.01 less than P less than 0.025). CONCLUSION: Sharp's radiographic scoring method seems to be more sensitive to change over time than is Larsen's method. The clinical importance of the change needs to be definitively established.

Adult↗
PubMed1992

[New concepts on the pathogenesis of uveitis].

The pathogenesis of uveitis is not entirely clear. Diverse clinical and experimental findings support the participation of immunologic mechanisms. In fact, uveitis may appear along with many immunologic systemic diseases. In this article, possible etiologic agents of uveitis are described and experimental models discussed. The immunologic mechanisms are analyzed and a unifying hypothesis is presented.

Animals↗
PubMed1991

[Interstitial pulmonary involvement in rheumatoid arthritis. Analysis by bronchoalveolar lavage].

We analyzed the results of bronchoalveolar lavage (BAL) in 14 patients with Rheumatoid Arthritis. Ten patients had total cell counts above 10 x 10(6)/100 ml and or more than 10% lymphocytes in differential counts. 40% of patients with normal clinical findings on pulmonary examination and normal A-a O2 gradients had abnormal BAL findings. These findings support the theory that pulmonary fibrosis in patients with RA may start with alveolitis, probably a lymphocytic type in 60% of cases. BAL may help early diagnosis and treatment monitoring.

Adult↗