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Biomedical subjects

A P Andonopoulos

Publications and source records attributed to A P Andonopoulos.

At least 19 recordsLinked to original sources
PubMed2006

In vitro effects of non-steroidal anti-inflammatory drugs on cytokine, prostanoid and matrix metalloproteinase production by interface membranes from loose hip or knee endoprostheses.

OBJECTIVE: To study the effects of the non-steroidal anti-inflammatory drugs (NSAIDs) aceclofenac, piroxicam, tenoxicam and indomethacin on cytokine, matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and prostaglandin E2 (PGE2) production, by interface membranes (IFT), obtained at revision surgery for aseptic loosening of total joint arthroplasty. Involvement of these soluble factors is well documented and probably, a pharmaceutically induced inhibition of them might retard loosening. METHODS: IFTs from 10 patients with a loose hip or knee endoprosthesis were collected. The possibility of septic loosening was thoroughly excluded by histopathologic and microbiologic evaluation. IFTs were cultured in the absence or presence of the tested drugs and the levels of the soluble mediators were determined, using electrophoretic and enzyme-linked immunosorbent assay techniques. Paracetamol was used as neutral drug. RESULTS: All NSAIDs exhibited a pronounced inhibitory effect upon the production of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). This specific effect on IL-6 is reported in the literature for the first time. The majority of NSAIDs also induced the production of IL-1beta in an adequate portion of samples. These drugs did not have a clear effect on MMP synthesis, but they had a stimulatory tendency on TIMP-1 production. Paracetamol, significantly decreased the synthesis of TNF-alpha and that of the gelatinases. CONCLUSION: Our in vitro results are encouraging, since it appears that the action of NSAIDs, globally considered, may be beneficial upon the loosening process. The inhibitory effect of paracetamol upon TNF-alpha and gelatinases is intriguing. Our data, if supported by similar observations, probably justify performance of long-term clinical trials.

Aged↗
PubMed2006

Increased expression of CD154 (CD40L) on stimulated T-cells from patients with psoriatic arthritis.

OBJECTIVES: CD40L is a costimulatory molecule and an early activation marker of T-lymphocytes. Based on the hypothesis that activated T-cells may play a role in the pathogenesis of psoriatic arthritis (PsA), we evaluated the level of CD40L expression on T-cells from patients with PsA. METHODS: We analysed 12 patients with PsA, six patients with rheumatoid arthritis (RA) and four healthy volunteers. T-cell surface expression of CD40L was evaluated using two-colour flow cytometry in (i) the resting state and (ii) following stimulation with phorbol myristate acetate/ionomycin, with or without ciclosporin (CsA)-mediated inhibition. RESULTS: Expression of CD40L was significantly increased on activated T-cells from patients with PsA, particularly those with active disease, when compared with normal individuals and patients with RA (mean percentages of CD3+ CD40L+ cells: 23.74, 11.59 and 9.57% for patients with active PsA, patients with RA and healthy volunteers, respectively). CsA-mediated inhibition of CD40L induction was equally effective in all study groups. CONCLUSION: CD40L is overexpressed on T-cells from patients with active PsA. This may indicate a role for CD40L in PsA pathogenesis. Larger-scale studies are warranted to address these issues.

Adult↗
PubMed2006

Mycophenolate mofetil as first-line treatment improves clinically evident early scleroderma lung disease.

OBJECTIVE: To find an effective, safe immunosuppressive regimen as an alternative to cyclophosphamide (Cy) for the treatment of clinically evident diffuse scleroderma (dSSc)-associated alveolitis of recent onset. METHODS: Five consecutive patients with dSSc and recent-onset alveolitis were enrolled and treated with mycophenolate mofetil (MMF) and small (< or =10 mg/day) doses of predinisolone in this open-label trial. One patient with long-standing fibrosing alveolitis was later added to our cohort. Pulmonary function tests [carbon monoxide diffusing capacity (DLCO) and forced vital capacity (FVC)], pulmonary high-resolution computed tomography (HRCT) scans and clinical assessment were performed before and at specified time-points after enrolment. Cases of significant infections, leucopenia and abdominal pain were recorded. RESULTS: After 4-6 months of MMF therapy, DLCO improved significantly compared with pre-treatment (mean DLCO 75.4% vs 64.2% of predicted value, respectively, P = 0.033). Values of FVC also improved, with the difference almost reaching levels of statistical significance (mean FVC 76.2% vs 65.6% of predicted value, P = 0.057). Ground glass opacities cleared in three of four patients with recent-onset alveolitis and were reduced in one patient after 6-8 months of treatment. Breathlessness and cough improved by 3 months. A possible treatment failure was seen in one patient. However, in five patients functional and clinical improvement was sustained during the study period. No adverse events were recorded in this ongoing clinical trial. CONCLUSION: Our preliminary data suggest that in patients with dSSc and recent, clinically apparent alveolitis, early treatment with MMF and small doses of corticosteroids (CS) may represent an effective, well-tolerated and safe alternative therapy.

Adolescent↗
PubMed2006

Autoantibodies against aggrecan in systemic rheumatic diseases.

OBJECTIVE: This study was undertaken to investigate the presence of autoantibodies against the main cartilage proteoglycan, aggrecan, in systemic rheumatic disease sera, and to identify substructure(s) responsible for the autoimmune response. METHODS: Sera were obtained from 86 patients with various systemic rheumatic diseases, 14 with osteoarthritis (OA), 18 with cancer and 40 healthy individuals. The presence of autoantibodies against aggrecan was examined by a solid phase assay and by Western blotting, using proteoglycan aggregates treated with proteolytic enzymes. The positive bands were subjected to nanohigh performance liquid chromatography (nanoHPLC)-MS, in order to identify the aggrecan substructures involved in the autoimmune response. RESULTS: Autoantibodies against aggrecan were identified in all systemic rheumatic disease sera at a high titre, almost three times that observed in healthy controls. OA and cancer sera produced a reaction equal to that of the healthy. Western blotting analysis of aggrecan proteolytic fragments revealed the presence of a triple band, reacting with the patients' sera, of about 37 kDa, which also reacted with a polyclonal antibody against hyaluronan-binding region. NanoHPLC-MS analysis suggested that this band belonged to the G2 domain of aggrecan. CONCLUSION: At least a part of the autoimmune reaction to aggrecan, displayed by the systemic disease sera, involves the G2 domain. The significant difference observed between these sera and those from other diseases, especially cancer, may suggest a possible discriminatory role of anti-aggrecan antibodies. This may help in the differential diagnosis in complicated clinical cases. However, for this to be confirmed, studies in larger cohorts of patients should be performed.

Adult↗
PubMed1998

Is a purified protein derivative skin test and subsequent antituberculous chemoprophylaxis really necessary in systemic rheumatic disease patients receiving corticosteroids?

Our objective was to determine whether a purified protein derivative (PPD) skin test and subsequent isoniazid administration to patients with systemic rheumatic disease, who react positively and are about to receive corticosteroids, is necessary. For this purpose, 451 unselected patients with systemic rheumatic diseases, such as rheumatoid arthritis, giant cell arteritis, polymyalgia rheumatica, systemic lupus erythematosus, scleroderma, poly- and dermatomyositis, mixed connective tissue disease, eosinophilic fasciitis, systemic necrotising vasculitis and Behçet's disease, were observed over a 6-year period. All patients had been started on steroids after commencement of the study and had received the drug for at least 1 year by the end of the study. A chest X-ray was performed before entry, every 6 months for the first year and yearly thereafter. A PPD skin test had been performed in 40 patients by other physicians, but it was our policy to omit the test. We divided our patients into age groups by decades. Steroid dosage varied according to diagnosis and severity. An initial chest X-ray revealed old inactive tuberculosis in 65 patients. During the follow-up period, none of the patients exhibited clinical or radiological evidence of reactivations of tuberculosis. However, at least 184 of the patients would have had a positive PPD skin test reaction, if tested. This figure is derived from the results of several studies on Greek army recruits whose current ages correspond to those of our patients. In conclusion, our results suggest that screening with a PPD and isoniazid prophylaxis, with all the potential risks for those who test positive, may not be necessary in patients with systemic rheumatic disease who will receive steroids.

Adrenal Cortex Hormones↗
PubMed1998

Multiple spontaneous intracerebral hemorrhages in a patient with progressive systemic sclerosis.

A 64-year-old woman with a two-year history of diffuse scleroderma responsible for severe interstitial lung disease was admitted for recurrent loss of consciousness. Her treatment at the time consisted of a corticosteroid and monthly cyclophosphamide pulses. Computed tomography and magnetic resonance imaging of the brain revealed two hemorrhagic lesions in the left frontal and temporal lobes, respectively. Amyloidosis and/or vasculitis may have contributed to these lesions.

Aged↗
PubMed1998

Autonomic cardiovascular neuropathy in Sjögren's syndrome. A controlled study.

OBJECTIVE: To test patients with primary Sjögren's syndrome (SS) for evidence of autonomic neuropathy. METHODS: Thirty-two patients with primary SS and 22 age and sex matched healthy individuals were asked specific questions about symptoms suggestive of autonomic neuropathy, and were subjected to a battery of 5 cardiovascular tests: response of blood pressure to sustained hand grip, Valsalva maneuver, heart rate response to deep breathing, and heart rate and blood pressure response to standing up. The chi-squared test with Yates' correction and 95% confidence intervals were used for statistical analysis of the results. RESULTS: Sixteen patients (50%) had symptoms of autonomic neuropathy when specifically asked versus none of the controls (p < 0.0005). The frequency of abnormal responses to the tests was 68.8% in patients and 12.7% in controls (p < 0.0001). Severe autonomic cardiovascular neuropathy was found in 87.5% of the patients but in none of the healthy individuals (p < 0.0001). CONCLUSION: Our results suggest that autonomic neuropathy is a feature of a significant portion of the SS population, and such patients should have appropriate evaluation. Similarly, patients with unexplained autonomic neuropathy should be investigated for evidence of SS.

Adult↗
PubMed1997

Intrahepatic bile duct injury and nodular regenerative hyperplasia of the liver in a patient with polyarteritis nodosa.

Although involvement of the hepatic vasculature in patients with polyarteritis nodosa is not unusual, biliary manifestations are very rare. We describe a patient with polyarteritis nodosa presenting with a febrile cholestatic anicteric syndrome. Histological examination of the liver revealed necrotizing arteritis of small hepatic arteries associated with significant lesions of intrahepatic bile ducts of the sclerosing cholangitis type, i.e. fibrous collar around the ducts, periductal inflammation and ductal proliferation. Concomitant nodular regenerative hyperplasia was found, a condition which has rarely been described in association with polyarteritis nodosa. We think that hepatic arteritis compromising arterial blood flow to the liver was responsible for the most likely ischemic nature of the bile duct injury and the nodular regenerative hyperplasia seen in our patient.

Aged↗
PubMed1997

Sjögren's syndrome in patients with newly diagnosed untreated non-Hodgkin's lymphoma.

The purpose of the study was to detect cases of Sjögren's syndrome among newly diagnosed untreated patients with non-Hodgkin's lymphoma and, furthermore, to identify in such cases clinical and serologic features known to occur more frequently in Sjögren's syndrome patients who evolve into lymphoma. Accordingly, thirty-three cases of newly diagnosed non-Hodgkin's lymphoma, prior to any treatment administration, were thoroughly studied for evidence of Sjögren's syndrome. Immunophenotyping for T and B cells and kappa and lambda light chains was concomitantly performed on both lymphomatous tissues and minor salivary glands. There were 5 patients with T cell and 28 with B cell lymphoma of various histologic subtypes and grades. Two of the latter (7.1%) had a positive for Sjögren's syndrome minor labial salivary gland biopsy, positive responses to the specific questionnaires for both eye and mouth dryness and abnormal Schirmer's and rose Bengal eye tests, substantiating the diagnosis of Sjögren's syndrome. Both were male with lung and stomach non-Hodgkin's lymphoma respectively, enlargement of the lacrimal glands, monoclonal gammapathy of the IgM kappa type and, one of them had high titer and of fine speckled pattern positive antinuclear antibodies and anti-Ro(SSA) and anti-La(SSB) antibodies in his serum. A monotypic infiltrate with kappa light chain restriction, identical to that in the lymphomatous tissue of these two patients, was present in their minor salivary gland biopsy as well. Such a finding was not encountered in any of the remaining patients. Although our sample is relatively small, our results confirm the relationship between Sjögren's syndrome and non-Hodgkin's lymphoma, looked at from the opposite direction. Obviously, studies involving larger populations would be more definitive, regarding the issue of what percentage of this lymphoma patients originates from Sjögren's syndrome.

Adult↗
PubMed1996

Thyroid function and immune profile in rheumatoid arthritis. A controlled study.

The aim of our study was to determine the prevalence of thyroid dysfunction and autoimmune abnormalities in rheumatoid arthritis (RA) and to further investigate the possible association between D-penicillamine and autoimmune thyroiditis. For this purpose, one hundred and one unselected consecutive patients with RA and 70 age and sex matched controls were studied prospectively. Evaluation included a complete history and physical examination with special attention to symptoms suggestive of thyroid pathology, routine laboratory and serologic immune profile, plus determination of serum levels of thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), antibodies to thyroid peroxidase (AbTPO) and TSH receptor antibodies (TRAB). Serum thyroxine binding globulin (TBG) was measured in all subjects with high thyroid hormone levels, whereas free T3 and T4 concentrations were determined in all individuals with abnormal T3, T4, TSH or TBG. Six patients with hyperhyroidism, 3 with hypothyroidism and 1 with the euthyroid hyperthyroxinemia (EH) syndrome were found, whereas four of the controls had hyperthyroidism. Thirteen patients and 6 controls had high AbTPO levels whereas no one had high TRAB. No association was detected between thyroid abnormalities and any serologic RA finding. Furthermore, no correlation between thyroid dysfunction and elevated AbTPO's was found. A relatively high prevalence of thyroid dysfunction (9,9%) and subclinical autoimmune thyroiditis (12,9%), the latter indicated by elevated AbTPO's, was found in our RA patients. These figures were higher than those in the control group (5,7% and 8,6% respectively), but the difference did not reach statistical significance. Of further interest may be our finding that, despite anecdotal reports blaming D-penicillamine for cases of autoimmune thyroiditis, the incidence of the latter was similar among recipients and nonrecipients of the drug. Similarly, TRAB were not detected in any patient treated with D-penicillamine.

Adult↗
PubMed1995

Autonomic cardiovascular neuropathy in primary Sjögren's syndrome.

The case of a 65-year-old female with primary Sjögren's syndrome and severe autonomic cardiovascular neuropathy, manifested by incapacitating postural hypotension, is presented. It is postulated that the patient's Sjögren's syndrome was responsible for the autonomic neuropathy, probably via a vasculitic mechanism. Treatment with hydrocortisone resulted in improvement in the patient's symptoms but it did not significantly alter the objective findings of autonomic dysfunction. We suggest that it is probably worth studying Sjögren's patients for evidence of autonomic neuropathy.

Aged↗