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Biomedical subjects

M Cuchacovich

Publications and source records attributed to M Cuchacovich.

33 records · Page 2Linked to original sources

[Neurologic involvement in Reiter's disease. Report of 2 cases].

Neurologic involvements is a rare complication of Reiter syndrome. It may precede other manifestations and constitutes a cause of death. We report 2 cases. The first, an 18 year-old male developed arthritis, fever, balanitis and sacroileitis 2 months after non gonococcal urethritis. He received phenylbutazone and local steroids without improvement. Logic dysphagia, diplopia with bilateral paralysis of the IV and VI cranial nerves and generalized absent reflexes developed gradually 2 weeks after admission. Methylprednisolone pulses failed to improve the patient's condition and plasmapheresis was associated to near complete remission after 6 exchanges. The other patient, a 31 year old male started out with alternating lower extremity paresis. One month later, urethritis, conjunctivitis, arthritis and sacroileitis appeared. The electromyogram was characteristic of axon sensorimotor polyneuropathy. Administration of naproxen was associated to complete improvement within 2 weeks. Neither patient had shown evidence of recurrence after a 5 year follow up period.

Adolescent↗

Intraarticular progesterone inhibits 3H-dexamethasone binding to synovial cells from patients with rheumatoid arthritis. A study by dry radioautographic technique.

Glucocorticoids are known to exert their antiinflammatory effects through an interaction with specific hormone receptors. Progesterone is able to bind to these glucocorticoid receptors exerting either agonistic or antagonistic actions. We have reported that a single intraarticular injection of progesterone exerts a local antiinflammatory action in patients with rheumatoid arthritis (RA), suggesting an agonistic effect of progesterone on local glucocorticoid receptors. To corroborate this possible mechanism of action, we investigated the binding of 3H-dexamethasone to local glucocorticoid receptors in synovial tissue from 3 patients with active RA, before and 14 days after a single intraarticular injection of progesterone. Both cytoplasmic and nuclear 3H-dexamethasone binding sites were observed within synoviocytes, macrophages, fibroblasts, lymphocytes and endothelial cells. Dry radioautograms of biopsied synovial tissue demonstrated a marked decrease of 3H-dexamethasone binding following progesterone treatment in all patients (p less than 0.001 for each comparison). Although the number of cases is not large enough to draw definitive conclusions, our data confirm the marked anti-inflammatory effect of intraarticular progesterone and support the hypothesis of an agonistic effect of progesterone (or its metabolites) on glucocorticoid receptors.

Arthritis, Rheumatoid↗

Radiologic progression during intramuscular methotrexate treatment of rheumatoid arthritis.

The radiographic evolution of joint lesions in 41 patients with severe and longstanding rheumatoid arthritis (RA) (mean duration: 12.9 years) treated with methotrexate (MTX) for more than 24 months (mean 31.2 months) was studied in a double blind manner by 2 rheumatologists using Larsen's score. All the patients were clinically improved. The radiological study of hands and wrists was possible in only 37 of 41 patients for surgical reasons. We found a deterioration of joint lesions in 31 cases (83.8%), a stabilization in 6 cases (16.2%). MTX does not appear to be able to slow down the radiographic evolution of RA. Whether it could prevent the radiologic progression in early RA remains to be elucidated.

Adult↗

[Patients with primary anterior uveitis. Determination of circulating immune complexes].

The level of circulating immune complexes (CIC) in 31 patients with primary anterior uveitis was determined by an ELISA method (C1q in solid phase). In addition, we measured antinuclear antibodies (ANA), HLAB 27, C3 and C4. Increased levels of CIC were found in 38% of patients (Group I), the remainder had normal levels (Group II). Positive ANA were found in 33% of patients in Group I and 26% of patients in Group II. The clinical findings and course of uveitis was similar in both groups. Chronic uveitis was associated to greater levels of CIC as compared to recurrent uveitis among patients in Group I (p less than 0.0001). Also, moderate sequelae from uveitis were associated to higher CIC levels.

Adolescent↗

[Headache of cervical origin].

We studied 40 patients with cervical spine disease who had headache (Group A) with 40 patients with disease and no headache (Group B). In addition to clinical and radiologic evaluation, 24 patients in group A and 27 in Group B had electromyographic study, which was normal en 18 of the former and 4 of the latter group. Abnormal neurologic findings were present only in Group B (37% of patients). Alterations of the cervical spine were more pronounced in Group B. These findings suggest that headache is not related to cervical spine disease and may be caused by other factors such as inadequate posture, brisk movements of the neck and emotional and psychologic disturbances.

Adult↗

Intraarticular progesterone: effects of a local treatment for rheumatoid arthritis.

The antiinflammatory effect of a single intraarticular injection of progesterone was investigated in 12 patients with rheumatoid arthritis. A local, but no systemic decline of inflammation was observed in 10 of them for at least one month. The average local scores of inflammation at Days 7, 14, 21 and 30 after injection were significantly lower than pretreatment scores (p less than 0.000003 for each comparison). In some patients the effect continued for up to 2 months. No important side effects were observed during the following 2 months. However, a more prolonged followup of treated patients is necessary to rule out the late onset of side effects.

Arthritis, Rheumatoid↗

HLA in Chileans with intrahepatic cholestasis of pregnancy.

A possible association between intrahepatic cholestasis of pregnancy (ICP) and human-leukocyte histocompatibility (HLA) antigens--used as genetic markers--was studied in 100 women with ICP compared to 100 multiparous women without a past history of the disease. Because we previously found a higher frequency of ICP in women with an overt Araucanian Indian descent than in Chilean Caucasoids, women from both ethnic groups were studied. Among the 37 specificities of the HLA system studied (17 of HLA-A, 16 of HLA-B, and 4 of HLA-C series), only HLA-BW16 showed a tendency to be more frequent in women with ICP rather than in control women. This finding appears to be related with ethnic origin and not ICP, HLA-BW16 was significantly more frequent in women with Araucanian Indian descent (43.4%) than in Chilean Caucasoids (16.3%) (p less than 0.01). The high frequency of HLA-BW16 in the predominantly Caucasoid population in Chile, in comparison with Caucasians in Europe and in North America, may be another indicator of their ethnic admixture with aborigine groups. The high frequency of HLA-BW16 reported in North American Indian-admixed groups (16%) suggests that HLA-BW16 may be a genetic characteristic common to some aboriginal populations in North and South America.

ABO Blood-Group System↗

Systemic vasculitis associated with Fasciola hepatica infection.

We report the case of a 50-year-old man who presented with systemic vasculitis associated with Fasciola hepatica infection. The patient presented with severe skin, kidney, spleen, ophthalmic, and neurological compromise. An immunological examination for primary vasculitis was negative and other infections were discounted by microbiological and serological analyses. The patient was treated with steroids without clinical response. The Fasciola hepatica infection was confirmed by the presence of specific immunoglobulin G (IgG) serum antibodies detected by a quantitative enzyme-linked immunosorbent assay (ELISA) with an optical density (OD) of 0.483 OD units (normal value<0.170 OD units) and a high-titre complement fixation (1/80 dilution). The patient received treatment with triclabendazole and all symptoms and systemic manifestations resolved within weeks. Hence, this previously unreported vasculitis-associated infection, if identified opportunely, can be treated and cured.

Animals↗

Characterization of human serum dipeptidyl peptidase IV (CD26) and analysis of its autoantibodies in patients with rheumatoid arthritis and other autoimmune diseases.

OBJECTIVES: To assess the serum levels, specific activity and other characteristics of dipeptidylpeptidase IV (DPP IV/CD26), an ectoenzyme that plays a critical role in the modulation and expression of autoimmune and inflammatory diseases, from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjögren syndrome (SS) and normal controls. To study the possible underlying molecular basis if significant differences were found. METHODS: Serum DPP IV was purified by ion-exchange and affinity chromatography techniques and its specific activity and sera levels were determined by an enzyme-linked assay (ELISA). The enzyme was further analyzed for its sialic acid content, its adenosine deaminase binding capacity and its electrophoretic mobility. The levels of circulating IgA, IgG, and IgM anti-DPP IV autoantibodies were determined by an ELISA technique. RESULTS: The median serum levels of DPP IV in RA patients was similar to controls (0.85 microg/ml versus 1.03 microg/ml, p = n.s.); in SLE and SS patients the enzyme serum levels were reduced to nearly one half of controls (p < 0.001). DPP IV specific activity was significantly reduced in serafrom RA patients when compared with those of SLE, SS and normal sera (12.24 versus 16.5, 19.69 and 16.34 mol pNA x 10(-4)/min/mol respectively, p < 0.005). Both RA and SLE enzymes were hypersialylated, but only RA DPP IV augmented its specific activity to close to control values after desialylation with V. cholerae neuraminidase. Sera from all patient groups contained anti-DPP IV autoantibodies, but only those of the IgA isotype were significantly higher than those found in normal subjects. CONCLUSION: The specific activity of serum DPP IV was decreased only in RA patients, although its levels were similar to normal controls. While both RA and SLE DPP IV were hypersialylated, desialylation restored the specific activity only of RA DPP IV. This finding suggests that different specific glycosylation sites in the enzyme might be involved as the underlying mechanism of the decreased enzyme specific activity of RA patients. The differences in DPP IV levels observed between RA and SLE patients seem to reflect a different status of T cell activation in both diseases.

Arthritis, Rheumatoid↗

Behçet's disease patients present high levels of deglycosylated anti-lipoteichoic acid IgG and high IL-8 production after lipoteichoic acid stimulation.

OBJECTIVES: Lipoteichoic acid (LTA), induces some of the clinical symptoms of Behçet's disease (BD) in a rat animal model. These results led to the hypothesis that LTA may also trigger BD in humans. We investigated the humoral and cellular immune response against LTA and lipopolysaccharide (LPS) in patients with BD, and compared these responses with those of patients with active chronic oral ulcers (OU) and normal controls. METHODS: Samples were obtained from 12 active BD, 12 inactive BD, 12 active OU and 12 normal controls. Anti-LTA, anti-LPS antibodies levels and the capacity of immune complexes anti-LTA IgG-LTA to activate complement were studied. Exposed mannose residues in anti-LTA IgG were analyzed in the four groups. The interleukin-8 (IL-8) production by peripheral blood mononuclear cells cultures after LTA and LPS stimulation was also studied in all groups. RESULTS: The capacity to bind mannan binding protein (MBP) of anti-LTA IgGs was significantly higher in BD and active OU patients relative to normal controls (p < 0.001). However, only active BD patients generated significantly higher levels of C5a than controls (p < 0.0001). The IgGs purified from the sera of BD patients showed a high specificity for LTA from Streptococcus sanguis or Streptococcus faecalis. LTA also stimulates the secretion of IL-8 in peripheral blood mononuclear cells isolated from active BD patients. Anti-LPS IgA and IgG titers were significantly higher only in active OU patients relative to normal controls (p < 0.0018). CONCLUSION: These results suggest a mechanism involving LTA from streptococci in the pathogenesis of BD.

Adult↗

Growth factor activity of IL-6 in the synovial fluid of patients with rheumatoid arthritis.

OBJECTIVE: We set out to determine whether the ability of synovial fluids (SF) in patients with rheumatoid arthritis (RA) to facilitate the proliferation of synovial tissue-derived fibroblastic cell lines was related to the presence of growth factors and/or cytokines. METHODS: The growth factor activity of 20 RA SF was measured by their ability to induce anchorage-independent growth of the rat NRK-49F (49F) fibroblastic strain. The presence of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) was also assessed using neutralising anti-TGF-beta or anti-PDGF-AB mAbs. Cytokines were measured by functional assays or ELISA: RESULTS: We observed a correlation between growth factor activity and the IL-6 levels in SF. Both were correlated to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in SF and serum. IL-6 (at concentrations above 10(4) U/ml), synergized with growth factors in the induction of the anchorage independent (AI) growth of 49F cells. Pretreatment of SF with a neutralising anti-IL-6 mAb substantially reduced the capacity of these SF to induce AI growth of 49F cells, confirming the growth factor activity of IL-6 in this test. In contrast, IL-6 alone or in association with PDGF, epidermal growth factor (EGF) or TGF-beta had no effect on the anchored growth of synovial tissue-derived fibroblasts, and treatment of SF with a neutralising anti-IL-6 mAb did not affect their ability to increase the growth rate of synovial tissue-derived fibroblasts. CONCLUSIONS: These results strongly suggest that IL-6 is responsible for the observed correlation between the growth factor activity of SF and inflammatory indexes such as ESR and CRP. However, neither IL-6 nor PDGF were responsible for the observed positive effect of SF on synovial fibroblastic cell lines.

Adult↗