Search PubMed⌕ Search

Biomedical subjects

J Rovensky

Publications and source records attributed to J Rovensky.

At least 19 recordsLinked to original sources

Autoimmune hemolytic anaemia in the antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a multisystem disease with recurrent thrombosis in the presence of antiphosphlipid antibodies, which may include cardiac, neurological, gastrointestinal, hematologic or cutaneous manifestations. The occurrence of autoimmune hemolytic anaemia (AIHA) in APS has not been well established. The purpose of this study was to review the occurrence of AIHA in patients with APS and its relation to other disease manifestations. Three-hundred and eight patients with APS from seven medical centers in Israel, Serbia and the Slovac Republic were included and evaluated for associations between AIHA and various manifestations of APS. AIHA was documented in 32 patients (10.4%). The odds ration for AIHA was increased in the presence of anticardiolipin antibodies and livedo reticularis (5.4 and 7.8, respectively). There was a highly significant association between AIHA and cardiac valvular vegetations and thickening (P < 0.0001), arterial thrombosis (P < 0.02), livedo reticularis (P < 0.0001) and CNS signs of epilepsy or chorea (P < 0.02 and P < 0.03, respectively). Thus, APS patients with AIHA are at risk of developing these manifestations, and should therefore be investigated for them. In addition, the occurrence of AIHA may define a subgroup of patients with a significant risk for subsequent development of SLE.

Adult↗

Polymyalgia rheumatica and temporal arteritis: the endocrine relations and the pathogenesis. Review.

Polymyalgia rheumatica (PMR) and giant cell or temporal arteritis (TA) are related chronic inflammatory conditions which typically affect the aged subjects. Typical features of PMR include general symptoms of inflammation as well as severe muscle pain in shoulder and pelvic girdle. The manifestation of TA depends on localization of affected artery, usually branch vessels of the aortic arch. Etiology of PMR and TA remains unclear. The association with HLA system and characteristics of the inflammatory response are discussed in this paper. Age related changes in neuroendocrine system could also represent a pathogenic factor in genetically disposed individuals. Complex bi-directional neuroendocrine-immune relations are further modified by ongoing chronic inflammation. Good clinical response to glucocorticoids in PMR patients supports the assumption that the actual levels of cortisol are lower than would be expected during ongoing inflammation. Moreover, decreased levels of adrenal androgens have been observed in PMR and thus possible adrenal androgens supplementation during glucocorticoid treatment sketches new prospects for the treatment of PMR and TA.

Aged↗

Anti-serum amyloid component P antibodies in patients with systemic lupus erythematosus correlate with disease activity.

OBJECTIVE: To determine the presence of raised titres of anti-serum amyloid P component (SAP) antibodies in patients with systemic lupus erythematosus (SLE) and to evaluate their correlation with clinical disease by the SLEDAI and clinical manifestations. METHODS: 452 samples were screened for raised anti-SAP antibody titres by an ELISA. Clinical measures and SLEDAI scores were independently reviewed from medical records. 21 serial samples from 7 patients with SLE were assessed for a change in anti-SAP antibody titres after treatment. RESULTS: Raised anti-SAP antibody titres were detected in 145/328 (44%) SLE samples. In 112 randomly selected samples, 69/112 (62%) patients had raised anti-SAP antibodies and anti-dsDNA antibody titres, whereas only 32/112 (28%) had raised anti-dsDNA antibody titres without raised anti-SAP antibody titres. The mean titre of anti-SAP antibodies in patients with active disease was higher than in patients with inactive disease and controls. SLEDAI scores, assessed in 54 patients, were raised in 26/31 (84%) patients with raised anti-SAP antibody titres. A SLEDAI score >or=8 was found in 16/31 (52%) patients with raised anti-SAP antibody titres but in only 5/23 (22%) patients without raised titres. No specific pattern of disease was detected in patients with or without raised titres of anti-SAP antibodies. Serial sampling from patients with active SLE and raised anti-SAP antibody titres showed that anti-SAP antibody titres decreased after treatment and correlated with clinical improvement. CONCLUSION: Raised anti-SAP antibody titres detected in patients with SLE correlate with disease activity and decrease with improvement of clinical disease, and thus may serve as an additional prognostic marker.

Adolescent↗

Close association between valvar heart disease and central nervous system manifestations in the antiphospholipid syndrome.

BACKGROUND: Heart valves lesions and central nervous system involvement are among the most common manifestations of the antiphospholipid syndrome (APS). OBJECTIVE: To evaluate possible interrelations between these manifestations in a large group of APS patients. METHODS: 284 APS patients were evaluated retrospectively, 159 of whom had primary APS. Cardiac-CNS associations were determined for the entire study population, and for subgroups of patients with primary APS or APS associated with systemic lupus erythematosus (SLE). RESULTS: Significant associations where found between cardiac vegetations and epilepsy (p < 0.02), and between cardiac valve thickening or dysfunction and migraine (p = 0.002). Borderline association was found between valvar vegetations and migraine (p = 0.09). A significant association was also found between all valvar lesions and stroke or transient ischaemic attacks. Subanalyses showed that patients with primary APS had significant associations between cardiac valve pathology and all CNS manifestations, while patients with APS associated with SLE had no such associations. CONCLUSIONS: The study suggests potential differences in biological behaviour between primary APS and APS associated with SLE. The presence of cardiac valve pathology may be a risk factor for several types of CNS involvement in PAPS.

Adolescent↗

Comparison of apoptosis and mortality measurements in peripheral blood mononuclear cells (PBMCs) using multiple methods.

Death through apoptosis is the main process by which aged cells that have lost their function are eliminated. Apoptotic cells are usually detected microscopically by changes in their morphology. However, determination of early apoptotic events is important for in vitro (and ex vivo) studies. The main objective of the present study is to find the most sensitive method for apoptosis detection in human peripheral blood mononuclear cells (PBMCs) by comparing six different methods following five different means of immunological stimulation at 3 and 5 days. Each of six apoptosis quantification methods, except the trypan blue exclusion test, is a combination of two stains, one for the specific detection of apoptotic cells and the other for the unspecific detection of dead cells. Values for apoptosis and mortality were compared with a reference method. The choice of apoptosis detection method is more important following 3 days of stimulation than after 5 days of stimulation (P=2x10(-6) versus P=1x10(-2)). In contrast, we find mortality measurements following the different means of stimulation highly significant at both 3 and 5 days (F2.28=7.9, P=1.4x10(-6) at 3 days and F2.28=8.5, P=4.5x10(-7) at 5 days). Variation as a result of the combination of specific PBMC stimulation and the method used to detect apoptosis is reduced considerably with time (F1.58+3.7, P+3x10(-7) at 3 days to F=1.58=0.97, P=0.5 at 5 days). Based on Tukey's test, YO-PRO-1 is the most sensitive stain for apoptosis and, when combined with 7-AAD, provides an accurate measure of apoptosis and mortality. In conclusion, we propose YO-PRO-1/7-AAD as a new combination and low-cost alternative for the sensitive detection of early apoptosis.

Antibodies↗

Low levels of dehydroepiandrosterone sulphate in plasma, and reduced sympathoadrenal response to hypoglycaemia in premenopausal women with rheumatoid arthritis.

OBJECTIVES: To evaluate the function of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in premenopausal women with rheumatoid arthritis (RA). METHODS: Insulin-induced hypoglycaemia (0.1 IU/kg) was produced in 15 glucocorticoid-naive patients with long term RA with low disease activity and in 14 healthy women matched for age and body mass index. Concentrations of glucose, adrenocorticotropic hormone (ACTH), cortisol, Delta4-androstenedione (ASD), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 17alpha-hydroxyprogesterone (17OHP), epinephrine (EPI), norepinephrine (NE), interleukin 6 (IL6), and tumour necrosis factor alpha (TNFalpha) were analysed in plasma. RESULTS: Patients had comparable responses of glucose, cortisol, ACTH, ASD, and 17OHP to hypoglycaemia, without any signs of hypothalamic insufficiency. Patients had lower basal DHEAS than controls (3.03 (0.37) micromol/l v 5.1 (0.9) micromol/l, respectively; p<0.05); borderline lower basal DHEA levels (p = 0.067); while the response of DHEA to hypoglycaemia was comparable to that of controls. Patients with RA had lower EPI (p = 0.005) and NE (p<0.001) responses to hypoglycaemia. TNFalpha and IL6 were higher (p<0.05) in patients with RA (TNFalpha 8 (2.8) pg/ml in RA v 1.1 (0.5) pg/ml in controls and IL6 15.1 (6.7) pg/ml v 1.4 (0.7) pg/ml). CONCLUSIONS: Lower basal DHEAS levels, without concomitant differences or changes in DHEA, ASD, 17OHP, and cortisol responses to hypoglycaemia in patients with RA, indicate an isolated decrease in adrenal androgen production. Significantly lower responses of EPI and NE to hypoglycaemia may suggest sympathoadrenal hyporeactivity in patients with RA.

Adrenocorticotropic Hormone↗

A comparison of the sensitivity of diagnostic criteria for polymyalgia rheumatica.

OBJECTIVE: To compare the performance of the several different diagnostic criteria sets currently in use for polymyalgia rheumatica (PMR). METHODS: 213 patients attending eight rheumatological centres in eight different European countries were studied. All had recently been referred and were considered by the senior investigator at each centre, selected because of their experience in treatment of PMR, to have this condition. By use of a standard international proforma, the requisite diagnostic points in each criteria set were sought. Sensitivity for each criterion from each set was then calculated, as well as the sensitivity of each criteria set as a whole. RESULTS: Of four criteria sets compared, the Bird (1979) criteria performed best with a sensitivity of 99.5%, and the Hunder (1982) criteria second best, with sensitivity of 93.3%. These both performed significantly better than the two other criteria sets, though each of these was admittedly developed for rather specialised reasons. CONCLUSIONS: Although this study compares homogeneity, we suggest the Bird 1979 or Hunder 1982 criteria should be used whenever possible. Studies that have used alternative criteria may have less sensitivity in diagnosis.

Adult↗

Peptide hormones and histamine in plasma and synovial fluid of patients with rheumatoid arthritis and osteoarthrosis.

OBJECTIVES: Hormones other than adrenal and gonadal steroids may play also a significant role in the pathogenesis of rheumatoid arthritis. The aim of this study was to investigate the levels of selected peptide hormones and histamine in synovial fluid of knee joints and in plasma of patients with rheumatoid arthritis and with osteoarthrosis. METHODS: The concentrations of insulin, C-peptide, prolactin, growth hormone, free triiodothyronine (FT3), thyrotropin (TSH), and histamine were determined in synovial fluid and plasma of 27 patients with rheumatoid arthritis (RA) and in 12 patients with osteoarthrosis (OA). RESULTS: The presence of peptide hormones in synovial fluid was demonstrated. The levels of TSH and growth hormone were lower in synovial fluid than in plasma in both groups, while those of prolactin were comparable in synovial fluid and in plasma. The levels of C-peptide (p < 0.05), insulin and FT3 were higher in synovial fluid than in plasma of OA patients, but lower in synovial fluid of RA patients as compared to their levels in plasma. Significant positive correlations between the levels in plasma and synovial fluid were observed in prolactin (p < 0.001, r = 0.741) and TSH (p < 0.05, r = 0.88) only. After age adjustment, no significant differences in synovial fluid and in plasma levels of all hormones were found between OA and RA patients. The levels of histamine in plasma were similar in RA and OA patients, in synovial fluid of both groups histamine was found in almost undetectable amounts. CONCLUSIONS: The selected peptide hormones, e.g. insulin, C-peptide, prolactin, growth hormone, FT3 and TSH, are present in synovial fluid of RA and OA patients, some of them in the concentrations comparable to these in plasma. The role of the locally present hormones in pathogenesis of RA has to be investigated in further studies and analyses.

Arthritis, Rheumatoid↗

Attenuated insulin response and normal insulin sensitivity in lean patients with ankylosing spondylitis.

Chronic low-grade inflammation is associated with insulin resistance. The aim of this study was to determine insulin response to intravenous glucose load and insulin sensitivity in patients with ankylosing spondylitis (AS). Fourteen nonobese male patients with AS and 14 matched healthy controls underwent frequent-sampling intravenous glucose tolerance test (FSIVGTT). Insulin secretion and insulin sensitivity were calculated using the computer-minimal and homeostasis-model assessment 2 (HOMA2) models. Fasting glucose, insulin, cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglyceride levels, HOMA2, glucose effectiveness, insulin sensitivity and insulin response to FSIVGTT did not differ between patients and controls. Tumor necrosis factor-alpha and interleukin (IL)-6 concentrations tended to be higher in AS patients than in controls. Second-phase beta-cell responsiveness was 37% lower (p = 0.05) in AS patients than in controls. A negative correlation was found between the percentage of beta-cell secretion and IL-6 in all subjects (r = -0.54, p = 0.006). We found normal insulin sensitivity but attenuated glucose utilization in the second phase of FSIVGTT in AS patients. Our results indicate that elevated IL-6 levels may play a pathophysiological role in attenuating beta-cell responsiveness, which may explain the association between elevated IL-6 levels and increased risk for type 2 diabetes.

Adult↗

Efficacy, safety and tolerability of lumiracoxib in patients with rheumatoid arthritis.

A randomised, double-blind study was performed to assess the efficacy and tolerability of lumiracoxib in patients with rheumatoid arthritis (RA). Patients received lumiracoxib 200mg once daily (o.d.) (n= 280), lumiracoxib 400mg o.d. (n= 281), naproxen 500 mg twice daily (n= 279) or placebo (n= 284) for 26 weeks. The primary efficacy variable was response to treatment according to ACR20 criteria (adjusted for prohibited concomitant or excessive rescue medication use and discontinuations due to unsatisfactory therapeutic response) at week 13. Safety and tolerability was also assessed. Significantly more patients receiving lumiracoxib than placebo were responders according to ACR20 criteria at week 13 (41.1 and 42.7% for lumiracoxib 200 and 400 mg o.d., respectively; 32.4% for placebo; both p < 0.05). The proportion responding to naproxen (39.1%) was not significantly different from placebo. Prespecified gastrointestinal adverse events were more frequent with naproxen than with either lumiracoxib dose or placebo. Lumiracoxib is therefore an effective and well-tolerated therapy for RA.

Adult↗

Hypothalamic-pituitary-adrenal axis function in ankylosing spondylitis.

OBJECTIVE: To assess basal function and responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in patients with ankylosing spondylitis during dynamic testing. METHODS: Insulin induced hypoglycaemia (IIH) (Actrapid HM 0.1 IU/kg, as intravenous bolus) was induced in 17 patients and 11 healthy controls matched for age, sex, and body mass index. Concentrations of glucose, adrenocorticotrophic hormone (ACTH), cortisol, insulin, dehydroepiandrosterone sulphate (DHEAS), 17alpha-hydroxyprogesterone, interleukin 6 (IL-6), and tumour necrosis factor alpha (TNFalpha) were determined in plasma. RESULTS: Comparable basal cortisol levels were found in the two groups, with a trend to be lower in ankylosing spondylitis. In the ankylosing spondylitis group, there were higher concentrations of IL-6 (mean (SEM): 16.6 (2.8) pg/ml v 1.41 (0.66) pg/ml in controls; p<0.001) and TNFalpha (8.5 (1.74) pg/ml v 4.08 (0.42) pg/ml in controls; p<0.01). Glucose, insulin, ACTH, DHEAS, and 17alpha-hydroxyprogesterone did not differ significantly from control. The IIH test was carried out successfully in 11 of the 17 patients with ankylosing spondylitis, and the ACTH and cortisol responses were comparable with control. General linear modelling showed a different course of glycaemia (p = 0.041) in the ankylosing spondylitis patients who met the criteria for a successful IIH test compared with the controls. CONCLUSIONS: The results suggest there is no difference in basal HPA axis activity and completely preserved responsiveness of the HPA axis in patients with ankylosing spondylitis. The interpretation of the different course of glycaemia during IIH in ankylosing spondylitis requires further investigation.

17-alpha-Hydroxyprogesterone↗

Prevalence of autoantibodies against structure specific recognition protein 1 in systemic lupus erythematosus.

Antibodies (Abs) against the structure specific recognition protein 1 (SSRP1) were reported in a small systemic lupus erythematosus (SLE) series but not in other systemic autoimmune diseases. The aim of the study was to confirm the selective presence of anti-SSRP1 Abs in a larger SLE series and to evaluate their relationship with disease activity and other immune markers. Anti-SSRP1 Abs were investigated by a 'home made' ELISA in: 120 SLE, 65 rheumatoid arthritis (RA), 51 systemic sclerosis (SSc), 23 Churg-Strauss syndrome (CSS) and 40 idiopathic autoimmune urticaria (IAU) patients and 190 healthy controls. Sera from MRL lpr/lpr and Balb-c mice were also tested. Anti-SSRP1 Abs were detected in 43 SLE (35.8%), nine SSc (17.6%), eight RA (12.3%), six IAU (15%), three CSS (13%) patients and five healthy controls (2.6%). Antibody prevalence and titers were significantly higher in SLE patients than in sera from both normal and disease controls. Anti-SSRP1 Ab activity was also detected in sera from MRL lpr/lpr but not Balb-c mice. The antibodies did not correlate with the disease activity evaluated as the ECLAM index score and were more prevalent in patients without renal involvement. No correlation was found with other serum autoantibodies. Our results confirm that anti-SSRP1 Abs are associated with but not specific for the lupus disease.

Adolescent↗

Growth hormone and prolactin responses during partial and whole body warm-water immersions.

AIM: To elucidate the role of core and skin thermoreceptors in the release of growth hormone (GH) and prolactin (PRL), a sequence of two experiments using whole-body (head-out) and partial (one forearm) hot water immersions was performed. METHODS: Experiment 1: Nine healthy men were exposed to head-out and partial water immersions (25 min, 38-39 degrees C). RESULTS: Head-out immersion increased the core temperature (38.0 +/- 0.1 vs. 36.7 +/- 0.1 degrees C, P < 0.001) and plasma concentration of the hormones (GH, 16.1 +/- 4.5 vs. 1.2 +/- 0.4 ng mL(-1), P < 0.01; PRL, 9.1 +/- 1.0 vs. 6.4 +/- 0.4 ng mL(-1), P < 0.05). During the partial immersion the core temperature was slightly elevated (36.8 +/- 0.1 vs. 36.6 +/- 0.1, P < 0.001), the concentration of GH increased (4.8 +/- 1.7 vs. 0.6 +/- 0.3, P < 0.05), while plasma PRL decreased (7.6 +/- 0.8, 6.0 +/- 0.6, 5.2 +/- 0.6, P < 0.01). Experiment 2: Seven volunteers immersed one forearm once in 39 degrees C and once in 38 degrees C water. The measurements were performed in 5-min intervals. The GH concentration increased gradually from the beginning of the immersions (min 10; 39 degrees C: 1.9 +/- 1.0 vs. 0.6 +/- 0.3 ng mL(-1), P < 0.01; 38 degrees C: 0.19 +/- 0.03 vs. 0.14 +/- 0.03, P < 0.05) and peaked after their completion (39 degrees C: +10 min, 3.7 +/- 2.0, P < 0.001; 38 degrees C: +15 min, 0.86 +/- 0.61, P < 0.01). The core temperature was unchanged until min 15 of the 39 degrees C bath. Thereafter, it increased about 0.15 degrees C above the baseline (P < 0.01). Immersion in 38 degrees C water did not induce core temperature changes. CONCLUSIONS: Peripheral thermoreceptors are involved in GH release when the body is exposed to elevated environmental temperature while a substantial elevation of core temperature is a precondition of PRL release.

Adult↗

EULAR response criteria for polymyalgia rheumatica: results of an initiative of the European Collaborating Polymyalgia Rheumatica Group (subcommittee of ESCISIT).

OBJECTIVE: To develop response criteria for polymyalgia rheumatica (PMR) for monitoring treatment and comparing alternative treatments regimens. METHODS: 76 patients, mean (SD) age 68.7 (7.7) years, were enrolled. Corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) were the only drugs allowed during the observation period. Erythrocyte sedimentation rate (ESR), C reactive protein (CRP), alpha(2) globulin, serum iron, pain, physician's global assessment (PGA), morning stiffness (MST), muscle tenderness (MT), myalgia, and the elevation of upper limbs (EUL) were determined regularly. The daily corticosteroid and NSAID doses as the corticosteroid response time were recorded. To ensure evaluation of an adequate number of patients (n = 57) week 24 was chosen for final analysis. RESULTS: ESR, CRP, alpha(2) globulin, pain, PGA, MST, myalgia, MT, and EUL showed significant improvement (p<0.0001) at week 24 compared with week 0. Multiple regression analysis showed that changes of ESR (p = 0.08), CRP (p = 0.41), alpha(2) globulin (p = 0.13), MST (p = 0.1), and MT (p = 0.07) were independent of pain, but myalgia (p<0.001) and EUL (p = 0.003) were pain dependent. Consequently, a core set of PMR response criteria, comprising ESR or CRP, pain, PGA, MST, and EUL was established. Assessment of treatment responses with this core set resulted in 90%, 70%, 50%, and 20% improvement in 31/57 (54%), 46/57 (81%), 51/57 (89%), and 54/57 (95%) of the patients, respectively. CONCLUSION: These PMR response criteria are a promising tool for better monitoring of disease activity and treatment in PMR. It is proposed that these criteria should be used in clinical trials in the near future to explore alternative treatment options for PMR.

Adrenal Cortex Hormones↗