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Biomedical subjects

M Mavrikakis

Publications and source records attributed to M Mavrikakis.

At least 19 recordsLinked to original sources

Circulating P- and L-selectin and T-lymphocyte activation and patients with autoimmune rheumatic diseases.

Circulating levels of P- and L-selectins and the degree of T-lymphocyte activation were assessed by enzyme-linked immunosorbent assays in 75 selected patients with rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) at various clinical stages, and in 40 healthy blood donors matched for age and gender. Mean levels of P-selectin were significantly higher than normal in RA (lower in patients with clinical remission) and SSc (higher in patients with early-onset diffuse disease), but not in SLE. In contrast, mean L-selectin levels were significantly higher than normal in SLE (no correlation to the degree of disease activity), but not in RA or SSc. Mean levels of soluble interleukin-2 receptors (sIL-2R), reflecting mainly T-lymphocyte activation, in patients with active RA, SSc and SLE were almost double the normal level; however, correlations between individual levels of circulating P- or L-selectins and sIL-2R within groups revealed a strong positive correlation only between L-selectin and sIL-2R (r = 0.66, p<0.001), and only in patients with SLE. Given the different expression of P- and L-selectins, these findings indicate a distinct pattern of immune cell activation in chronic diseases that share an overactivation of T-lymphocytes. The possible clinical value of quantitation of circulating P-selectin in patients with RA and SSc on the one hand, and L-selectin in patients with SLE on the other, should be investigated by prospective studies.

Adult

Short-term estrogen administration improves abnormal endothelial function in women with systemic sclerosis and Raynaud's phenomenon.

BACKGROUND: Morphologic changes of the vascular endothelium are common in patients with systemic sclerosis and Raynaud's phenomenon. The aim of this study was to evaluate the endothelium-dependent vasodilatation and endothelium-independent vasodilatation and to examine the effects of short-term estrogen administration on vascular responses in these patients. METHODS AND RESULTS: The study included 12 female patients with systemic sclerosis and Raynaud's phenomenon (aged 49+/-14 years) and 12 age- and sex-matched healthy control subjects. With the use of high-resolution ultrasound imaging, brachial artery diameter was measured at rest, during reactive hyperemia (endothelium-dependent response), and after administration of sublingual nitroglycerin (endothelium-independent dilatation). Intima-media thickness of the common carotid artery was also measured. Baseline diameter was similar in patients and control subjects; intima-media thickness was significantly higher in patients (0.83+/-0.3 vs 0.46+/-0.2 mm, P= .002) than in control subjects. Flow-mediated dilatation was reduced in patients (3.6%+/-7% vs 11.9%+/- 4.6%, P = .003); endothelium-independent dilatation also was reduced in patients with Raynaud's phenomenon (14%+/-7% vs 23%+/-6%, P= .003). Vascular responses in 10 patients were examined 15 minutes after administration of conjugated estrogens (25 mg intravenously); there was a significant increase of endothelium-dependent dilatation after estrogen administration (1.7%+/-4% to 6.3%+/-4%, P= .01), whereas endothelium-independent dilatation did not change (13.4%+/-8% to 15.5%+/-7%, not significant). CONCLUSIONS: Endothelium-dependent vasodilatation and endothelium-independent vasodilatation are impaired in patients with Raynaud's phenomenon secondary to systemic sclerosis, whereas intima-media thickness is increased. Short-term estrogen administration can improve endothelial dysfunction in this group of patients.

Adult

Effects of 2-chlorodeoxyadenosine and gold sodium thiomalate on human bcl-2 gene expression.

Aberrant expression of apoptosis-related genes, including the "cell death suppressor gene" bcl-2, may play an important pathogenetic role in cancer and autoimmune diseases, In vivo upregulation of bcl-2 mRNA in synovial lining cells of patients with rheumatoid arthritis but not in patients with osteoarthritis has been recently found. In the present study we investigated whether agents exerting beneficial effects in patients with rheumatoid arthritis, namely the long used Gold Sodium Thiomalate (GST) and the novel immunosuppressive, purine analogue 2-chlorodeoxyadenosine (2-CdA), a lymphocyte apoptosis-inducing agent interfere directly with induction of bcl-2 mRNA expression. The phytohemagglutinin (PHA)-induced in vitro proliferation of normal human peripheral blood lymphocytes was significantly inhibited by non-toxic concentrations of 2-CdA and GST which are within the range of in vivo plasma concentrations in patients receiving the respective treatment. Using mRNA dot-blot analysis and hybridization with an IL-2-specific probe we found that GST, similarly to dexamethasone that served as control, suppressed the PHA-induced IL-2 mRNA accumulation dose-dependently. In contrast, 2-CdA (0.1 microgram/ml) at concentrations that inhibit by 80-90% the PHA-induced proliferative responses of lymphocytes did not affect IL-2 mRNA accumulation. Hybridization with a bcl-2-specific probe showed that the activation-induced accumulation and kinetics of bcl-2 mRNA were not changed in the presence of a wide range of concentrations of either GST or 2-CdA. Similarly, the mRNA accumulation of the "house-keeping" control gene beta-action remained unchanged by both agents. These findings indicate that biosynthesis of bcl-2 is not specifically affected by GST and CdA, suggesting that the immunomodulating effects of these agents, including their efficacy in suppressing chronic arthritis, are not related with a bcl-2-dependent mechanism.

Actins

Microfilaremia from a Dirofilaria-like parasite in Greece. Case report.

In Europe, zoonotic filarial infections in humans are caused by two species, Dirofilaria immitis and Dirofilaria repens. These parasites are associated mainly with embolic infarcts of the pulmonary artery and subcutaneous nodules, respectively. An unusual dirofilarial infection in a Greek patient who showed marked eosinophilia and microfilaremia is presented. Although the identification of Dirofilaria species is not conclusive, this report is the first on a case of microfilaremia from a Dirofilaria infection in an immunocompetent patient.

Aged

Immunocytochemical detection of P-glycoprotein in the management of malignant effusions.

P-glycoprotein (P-gp), a cell membrane protein, has been found in multidrug-resistant cancer cells. A total of 104 smears from patients with breast-cancer-associated pleural effusions and ovarian-cancer-related peritoneal effusions were studied for P-gp with the antibody C-219 and the avidin-biotin-immunoperoxidase method. Samples were taken before and 3 and 7 days after intracavitary bleomycin therapy and reaccumulation of effusion was assessed at 30 days. Smears that were P-gp-negative by the 7th day were associated with a good 30-day response to bleomycin in the majority of cases, while P-gp-positive smears were associated with a significant reaccumulation of fluid at 30 days. P-gp status is a valuable prognostic indicator of response to intracavitary bleomycin treatment in effusions from breast or ovarian cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem

Electrophysiologic abnormalities of cardiac function in progressive systemic sclerosis.

The heart has been generally recognized as a target organ in progressive systemic sclerosis. Noninvasive studies have assessed the incidence and prognostic importance of cardiac arrhythmias in these patients. However, detailed exploration of the function of impulse formation and the conduction system of the heart in these patients has never been reported. Therefore, invasive electrophysiologic studies were performed in 30 patients with systemic sclerosis, all of whom had neither obvious cardiac involvement nor cardiac arrhythmias, and in 32 subjects with no evidence of heart disease, who served as a control group. Corrected sinus node recovery time in patients with systemic sclerosis was significantly longer (P < .001) than in the control group, as was the HV interval (P < .05). Of the 30 patients with systemic sclerosis, 10 had an HV interval of 60 ms or longer. In four patients with systemic sclerosis, the recorded AH interval exceeded 125 ms. The intra-atrial conduction time tended to increase to a significant degree (P < .05) in patients with systemic sclerosis. The interatrial conduction time was much longer (P < .001), and the maximal conduction delay to the atrioventricular junction and to the distal coronary sinus was much greater in the patients with systemic sclerosis than in the control group (P < .001 for both). Supraventricular tachyarrhythmias were induced in 15 patients with systemic sclerosis versus 3 control group subjects (P < .001). With respect to corrected sinus node recovery time, AH and HV intervals, atrial vulnerability, and ventricular tachycardia, 3 of the 30 patients with systemic sclerosis had abnormal findings in one of these parameters and 14 had abnormalities in more than one. These results suggest that a broad spectrum of electrophysiologic abnormalities is present in patients with systemic sclerosis, which can be revealed only by invasive studies. Furthermore, this study provides additional support for the hypothesis that diffuse myocardial involvement is characteristic of scleroderma patients, since a number of these patients showed more than one electrophysiologic defect.

Adolescent

Expression of insulin-like growth factor-I receptor and transferrin receptor by breast cancer cells in pleural effusion smears.

Smear preparations were made from cells harvested from pleural fluid from 90 patients with breast cancer and stained for transferrin receptor (TRFr) and insulin-like growth factor-I receptor (IGF-Ir) using an immunocytochemical technique. The results were correlated with those from 36 benign effusions smears. In malignant smears from the breast cancer cases TRFr was demonstrated in 84.4% of the cellular deposits and IGF-Ir in 91.1%. TRFr was demonstrated in two (11%) of the tuberculous effusion smears and in six (100%) effusions from patients with collagen disease. IGF-Ir was not demonstrated in any of the smears from patients with benign disease. The sensitivity and specificity of TRFr staining were 84.4% and 77.7%, respectively, and for IGF-Ir staining were 91.1% and 100%, respectively. The underlying metabolic changes in the tumour cells which give rise to positive staining with these markers are discussed.

Adenocarcinoma

Retinal toxicity in long term hydroxychloroquine treatment.

OBJECTIVE: To report clinical experience from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who were receiving recommended doses of hydroxychloroquine for more than six years, and were monitored for evidence of hydroxychloroquine related retinopathy every six months. METHODS: A prospective (and continuing) evaluation was made of the potential retinal toxicity of hydroxychloroquine in a cohort of 360 Greek patients followed for RA and SLE, 58 of whom have received long term treatment ( > six years). Fundoscopy, colour vision tests, dark adaptation tests, visual field testing, automated perimetry, and electroretinogram were performed every six months. RESULTS: Among 58 patients receiving hydroxychloroquine for more than six years, two relatively young women (3.5%), one treated for RA and the other treated for SLE, developed characteristic hydroxychloroquine related toxic retinal lesions after cumulative doses of 700 g (6.5 years) and 730 g (8 years) of hydroxychloroquine, respectively. Bilateral visual acuity was 6/6 and 6/7.5, respectively; both patients had normal colour perception. Despite an early diagnosis and cessation of treatment, permanent visual field paracentral scotomata in both patients, and persisting lesions in fluorescein angiography in the patient with SLE, were observed at 4.5 and 3 years of follow up, respectively. No other specific cases of hydroxychloroquine related retinopathy have to date been identified in the remaining 302 patients. CONCLUSION: Cases of irreversible, hydroxychloroquine related retinopathy in patients who did not receive overdoses have not been reported previously. The present observations in two relatively young patients should raise our concern regarding the long term usage of an increasingly popular medication in rheumatology practice.

Adult

Proarrhythmic effects of reactive hypoglycemia.

A patient with refractory atrioventricular nodal reentry tachycardia is reported in whom it was possible to document that reactive hypoglycemia was the trigger for aggravation of arrhythmia. Over a period of 6 years, a series of electrophysiological studies revealed that, when the patient was in a hypoglycemic state, initiation of tachycardia was easy and most importantly that tachycardla termination by extra-stimulus pacing always failed. Furthermore, atrial fibrillation was inducible or spontaneously occurred only when the blood glucose level was reduced by IV insulin administration.

Blood Glucose

Small airways dysfunction in systemic sclerosis. A controlled study.

A debate exists regarding the importance of small airways disease in systemic sclerosis, while smoking seems to have a major effect on the exact prevalence. In order to evaluate small airways dysfunction (SAD) in a pure systemic sclerosis population, we performed pulmonary function studies in 31 nonsmoking patients and 31 age- and sex-matched nonsmoking control subjects. Patients' FVC, TLC, and Dco mean values were significantly lower compared with the corresponding values of the controls (p less than 0.05), while there was no difference in MEF25, RV, and RV/TLC. Seven (22.6 percent) of 31 patients and four controls (a nonsignificant difference) had evidence of SAD, namely a maximum expiratory flow at 25 percent of vital capacity (MEF25) less than 60 percent of predicted. Positive correlation (p less than 0.001) was found between MEF25 and FEV1/FVC in the patients. Moreover, no differences were found in abnormal lung function patients with and those without SAD in demographic, clinical, roentgenologic, and serologic features and results of pulmonary function tests. These findings suggest that SAD in our patients is not a characteristic and early manifestation of systemic sclerosis and that, when present, it is not correlated with the severity of the pulmonary involvement in scleroderma.

Female

Electrophysiologic studies of the heart in patients with rheumatoid arthritis.

We investigated the electrophysiological properties of the heart in patients with definite or classical rheumatoid arthritis using programmed electrical stimulation techniques. Twelve patients with rheumatoid arthritis and without evidence of organic heart disease or arrhythmia detectable with serial electrocardiograms and 24-hour ambulatory electrocardiographic monitoring were compared with 12 control subjects. Stimulation was performed from the high right atrium and right ventricular apex at a drive cycle length of 600 msec and the recording sites included high right atrium, atrioventricular junction and distal coronary sinus. There was no statistically significant difference in the corrected sinus node recovery time between the study and control group of patients. Similarly, no differences from normal were found in the AH and HV intervals or in the atrial and ventricular refractoriness, whereas the atrioventricular nodal effective refractory period was higher in patients with rheumatoid arthritis, compared with the control group (338 +/- 38 vs 286 +/- 29, P less than 0.02). The atrial conduction time during basic cycle length had a tendency to increase from high right atrium to atrioventricular junction in the study group and reached statistical significance from high right atrium to coronary sinus (92 +/- 15 vs 74 +/- 14, P less than 0.05). Electrophysiologic differences between the study and control patients also included a greater increase in maximal intraatrial (40 +/- 13 vs 27 +/- 16, P less than 0.05) and interatrial conduction delay (54 +/- 16 vs 31 +/- 12, P less than 0.01) of early premature stimuli in patients with rheumatoid arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Thyroid and parathyroid response to subtotal thyroidectomy.

Hypocalcemia occurring a few days after total subtotal thyroidectomy has been attributed either to parathyroid insufficiency or to calcitonin release. To investigate this matter further, we measured serum calcium, phosphate, T3, T4, TSH, parathormone (PTH), calcitonin (CT) and cAMP, in 27 women aged 23 to 63 years, before and also 3 and 7 days after subtotal thyroidectomy for multinodular nontoxic goiter. Ca, T3 and T4 decreased, whereas TSH increased appropriately to the decrease in T4 and T3. There was no increase in PTH appropriate to the Ca decrease. In contrast, PTH, cAMP and CT showed statistically unsignificant tendency to decrease. It was concluded that hypocalcemia after thyroidectomy is not due to CT release, but rather to a relative PTH insufficiency.

Adult

Unilateral ureteric ligation in diabetic rats: a pathologic and morphometric study.

We studied the combined effect of unilateral ureteral ligation on the morphology and pathology of the contralateral kidney in normal and streptozotocin induced diabetic rats. In the diabetic group that underwent ligation of the right ureter the weight and volume of the left kidney was far greater, the tissue specific gravity far lower, while the percentage of affected glomeruli was significantly greater compared with control rats and those undergoing only ureteric ligation.

Animals