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Biomedical subjects

O Elkayam

Publications and source records attributed to O Elkayam.

At least 19 recordsLinked to original sources

Positive anti-cyclic citrullinated proteins and rheumatoid factor during active lung tuberculosis.

OBJECTIVES: To determine the prevalence of anti-cyclic citrullinated proteins (anti-CCP) and IgM rheumatoid factor (RF) in sera of patients with TB compared with healthy controls. PATIENTS AND METHODS: 47 consecutive patients with recently diagnosed active pulmonary TB and 39 healthy controls were studied. Data were collected by questionnaire on clinical features of the disease, duration of symptoms, fever, cough, arthralgia, myalgia, sicca symptoms. Serum samples were collected from patients before starting treatment for TB and frozen at -20 degrees C. Anti-CCP and IgM RF were evaluated by ELISA. RESULTS: The mean (SD) duration of TB related symptoms was 4.4 (1.7) months, 73% had fever, 94% a cough. Rheumatic symptoms were relatively rare: arthralgia (4%), myalgias (4%), eye and mouth dryness (2% and 9%, respectively). Mean (SD) levels of anti-CCP were significantly increased in patients with TB compared with controls: 44.9 (51) IU v 20 (7.3) IU (p = 0.002). Serum levels >40 U were found in 15/47 (32%) patients compared with 1/39 (2.6%) controls (p = 0.002). Mean (SD) serum levels of IgM RF were significantly increased in patients with TB: 17.8 (19) v 4.3 (5) (p<0.0001). IgM RF was positive (>6 IU) in 29/47 (62%) patients v 1/39 (2.6%) controls (p<0.0001). CONCLUSIONS: A significant proportion of patients with active TB have an increased titre of anti-CCP and IgM RF.

Acute Disease↗

Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells.

OBJECTIVES: Osteoarthritis (OA) is the Western world's leading cause of disability. Cyclo-oxygenase-2 (COX-2) inhibitors are efficient anti-inflammatory agents commonly used in the treatment of osteoarthritis. However, recent studies have shown that their long-term use may be limited due to cardiovascular toxicity. The anti-inflammatory efficacy of the phytochemical curcumin has been demonstrated in several in vitro and animal models. This study was undertaken to investigate whether curcumin augments the growth-inhibitory and pro-apoptotic effects of celecoxib in OA synovial adherent cells. METHODS: OA synovial adherent cells were prepared from human synovial tissue collected during total knee replacement surgery. The cells were exposed to different concentrations of celecoxib (0-40 mum), curcumin (0-20 mum) and their combination. Flow cytometric analysis was used to measure the percentage of cells with a subdiploid DNA content, the hallmark of apoptosis. COX-2 activity was assessed by measuring production of prostaglandin E(2) by enzyme-linked immunoassay. RESULTS: A synergistic effect was observed in inhibition of cell growth when the cells were exposed to various concentrations of celecoxib combined with curcumin. The inhibitory effect of the combination on cell growth was associated with an increased induction of apoptosis. The synergistic effect was mediated through a mechanism that involves inhibition of COX-2 activity. CONCLUSIONS: This effect may enable the use of celecoxib at lower and safer concentrations, and may pave the way for a novel combination treatment in osteoarthritis and other rheumatological disorders.

Anti-Inflammatory Agents, Non-Steroidal↗

Evoked potential studies in the antiphospholipid syndrome: differential diagnosis from multiple sclerosis.

BACKGROUND: The CNS manifestations of the antiphospholipid syndrome (APS) can mimic multiple sclerosis both clinically and radiologically. OBJECTIVE: To compare evoked potential studies in APS patients and patients with multiple sclerosis with similar neurological disability. METHODS: 30 APS patients with CNS manifestations and 33 patients with definite multiple sclerosis and similar neurological disability underwent studies of visual evoked potentials (VEP), somatosensory evoked potentials (SSEP) in the upper and lower limbs (UL, LL), and sympathetic skin responses (SSR) in the upper and lower limbs. RESULTS: The neurological manifestations in the APS patients included stroke (n = 17), transient ischaemic attacks (n = 10), and severe headache with multiple white matter lesions on brain MRI (n = 3). Abnormal SSEP (LL), and SSR (UL; LL) were seen in APS patients (37%, 27%, and 30%, respectively) but VEP and UL SSEP were rarely abnormal (10% and 6%, respectively in APS v 58% and 33% in multiple sclerosis; p = 0.0005, p = 0.008). Mean VEP latencies were more prolonged in multiple sclerosis (116 ms v 101 ms, p<0.001). Only one APS patient had abnormal findings in all three evoked potential studies, compared with seven patients in the multiple sclerosis group (p = 0.04) CONCLUSIONS: Abnormal VEPs are uncommon in APS in contrast to multiple sclerosis. Coexisting abnormalities in all other evoked potentials were similarly rare in APS. In patients with brain MRI findings compatible either with multiple sclerosis or APS, normal evoked potential tests, and especially a normal VEP, may support the diagnosis of APS.

Adult↗

Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying drugs, including TNF alpha blockers.

OBJECTIVE: To assess the efficacy and safety of vaccination against influenza virus in patients with rheumatoid arthritis, with special emphasis on the effect of disease modifying antirheumatic drugs (DMARDs), including tumour necrosis factor alpha (TNFalpha) blockers. METHODS: 82 rheumatoid patients and 30 healthy controls were vaccinated with a split-virion inactivated vaccine containing 15 mug haemagglutinin (HA) per dose of each of B/Hong Kong/330/2001 (HK), A/Panama/2007/99 (PAN), and A/New Caledonian/20/99 (NC). Disease activity was assessed by tender and swollen joint count, morning stiffness, evaluation of pain, Health Assessment Questionnaire, ESR, and C reactive protein on the day of vaccination and six weeks later. Haemagglutination inhibiting (HI) antibodies were tested by a standard WHO procedure. Response was defined as a fourfold or more rise in HI antibodies six weeks after vaccination, or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated to assess the immunity of the whole group. RESULTS: Six weeks after vaccination, a significant increase in GMT for each antigen was observed in both groups, this being higher in the healthy group for HK (p=0.004). The percentage of responders was lower in rheumatoid patients than healthy controls (significant for HK). The percentage of responders was not affected by prednisone or any DMARD, including methotrexate, infliximab, and etanercept. Indices of disease activity remained unchanged. CONCLUSIONS: Influenza virus vaccine generated a good humoral response in rheumatoid patients, although lower than in healthy controls. The response was not affected by the use of prednisone or DMARDs.

Antibodies, Viral↗

Modulation of autoreactive responses of peripheral blood lymphocytes of patients with systemic lupus erythematosus by peptides based on human and murine anti-DNA autoantibodies.

Two peptides, based on the sequences of the complementarity-determining regions (CDR) 1 and 3 of a pathogenic murine monoclonal anti-DNA autoatibody that bears the 16/6 idiotype (Id), were shown to either prevent or treat an already established systemic lupus erythematosus (SLE) in two murine models of lupus. Two additional peptides based on the human monoclonal anti-DNA, 16/6 Id were synthesized. This study was undertaken in order to investigate the ability of the CDR-based peptides to immunomodulate SLE-associated responses of peripheral blood lymphocytes (PBL) of SLE patients. PBL of 24 of the 62 SLE patients tested proliferated in vitro following stimulation with the human 16/6 Id. Peptides based on the CDRs of both the human and murine anti-DNA autoantibodies inhibited efficiently and specifically the 16/6 Id-induced proliferation and IL-2 production. The latter inhibitions correlated with an up-regulated production (by 2.5-3.5-fold) of the immunosuppressive cytokine, TGF-beta. Overall, the results of our study demonstrate that the CDR-based peptides are capable of down-regulating in vitro autoreactive T cell responses of PBL of SLE patients. Thus, these peptides are potential candidates for a novel specific treatment of SLE patients.

Adolescent↗

Active leflunomide metabolite inhibits interleukin 1beta, tumour necrosis factor alpha, nitric oxide, and metalloproteinase-3 production in activated human synovial tissue cultures.

BACKGROUND: Leflunomide is now an approved agent for the management of adult rheumatoid arthritis (RA). Its active metabolite A771726 inhibits de novo pyrimidine biosynthesis. Although considered to be an immunosuppressive agent, its mechanism of action remains obscure. OBJECTIVES: Evaluation of the leflunomide active metabolite A771726 (LEF) effect on interleukin 1beta (IL1beta), tumour necrosis factor (TNFalpha), nitric oxide (NO), and stromelysin (metalloproteinase-3 (MMP-3)) production by activated human synovial tissue in culture. METHODS: Synovial tissue was obtained during surgery from patients undergoing total knee replacement owing to RA or osteoarthritis (OA), cut into small pieces, and cultured in Petri dishes with test materials as previously described. IL1beta, TNFalpha, NO, and MMP-3 were measured in the culture media after 48 hours incubation with different doses of LEF by methods previously described. RESULTS: LEF (0.3, 3, and 9 micro g/ml) inhibited IL1beta production in the presence of lipopolysaccharide (LPS; 3 micro g/ml) in a dose dependent manner (p<0.01) at LEF 0.3 micro g/ml. TNFalpha production in the presence of IL1beta (1 ng/ml) was also inhibited in a dose dependent manner (p<0.05 at LEF 0.3 micro g/ml). NO and MMP-3 production in the presence of LPS (3 micro g/ml) was inhibited as well (p<0.01 at LEF 1 micro g/ml and at LEF 0.3 micro g/ml, respectively). Synovial cell viability evaluated by the tetrazolium salt XTT was unaffected by the LEF concentration used. There was no qualitative difference in the response of OA and RA synovial tissue. CONCLUSION: Leflunomide may modulate the rheumatoid articular process by inhibition of local production of IL1beta, TNFalpha, NO, and MMP-3.

Aged↗

Atypical cutaneous findings in a patient with systemic lupus erythematosus.

A previously diagnosed systemic lupus erythematosus patient presented with arthralgia, skin rash and muscular weakness. When treated with high-dose corticosteroids and methotrexate she improved, except for a persistent lesion in the hand which evolved into a profound ulcer, along with tender subcutaneous nodules in the calf. A skin biopsy disclosed necrotizing vasculitis with giant cell granuloma revealing acid fast positive bacteria on ziels nilsen staining. A chest X-ray disclosed miliary tuberculosis (TB). The patient was diagnosed as miliary TB with prominent cutaneous involvement and treated with four anti-tuberculous drugs with slow resolution of her systemic, pulmonary and skin signs.

Adult↗

The use of an oral fluid immunoglobulin G ELISA for the detection of Helicobacter pylori infection in children.

BACKGROUND: Enzyme linked immunosorbent assay (ELISA) evaluation of oral fluid immunoglobulin G (IgG) antibodies to Helicobacter pylori is a unique approach for both epidemiological studies and the diagnosis of infection, especially in children. The use of oral fluid sampling to evaluate specific H. pylori IgG antibodies has advantages over serum, including reduced biohazard risk and noninvasive collection. Oral fluid sampling is fast and involves minimal patient discomfort. Since children facilitate transmission of H. pylori infection, a simple, accurate, noninvasive diagnostic test is necessary for large epidemiologic studies. The aim of our study was to evaluate a new oral fluid ELISA for detection of IgG antibodies to H. pylori in children. MATERIALS AND METHODS: We compared this new oral fluid ELISA with the HM-CAPTM serum ELISA and gastric biopsy histology using 779 oral fluid samples from children collected at 11 clinical sites across the United States. This cohort included 315 children symptomatic for abdominal pain and 464 asymptomatic. All samples were evaluated in a double blind manner. The oral fluid ELISA demonstrated a sensitivity of 76.2% and a specificity of 94.0% in children 2 months old to 201/2 years, as compared with the HM-CAPTM serologic assay. The assay's sensitivity improved to 81.3% in children aged 5 or greater and the specificity remained at 94.0%. When compared with gastric biopsy histology in the same age group, the oral fluid ELISA demonstrated a sensitivity of 71.7% and a specificity of 90.4%. RESULTS: This new oral fluid ELISA is moderately sensitive and offers a very specific method for detecting H. pylori infection in older children, but it is of little value in children under the age of 5 years. CONCLUSIONS: Overall, we conclude that this oral fluid ELISA does not appear to be a helpful clinical tool for the diagnosis of H. pylori infection in children.

Adolescent↗

Safety and efficacy of vaccination against hepatitis B in patients with rheumatoid arthritis.

BACKGROUND: Hepatitis B infection and vaccination against it have been implicated in the potential triggering or flare of some autoimmune diseases, including rheumatoid arthritis (RA). However, the safety of hepatitis B vaccination in patients with pre-existing RA is not known. OBJECTIVES: To assess the safety and antibody response of immunisation with a recombinant DNA hepatitis B vaccine in patients with RA. PATIENTS AND METHODS: The study comprised 44 patients with RA, of whom 22 received three doses (the second and third dose being given after one and six months) of a recombinant DNA hepatitis B vaccine (study group) and 22 did not receive the vaccine (control group). Both groups had comparable proportions of women and similar mean age (51 years). Clinical assessment before and two and seven months after the first immunisation included evaluation of daytime pain with a 10 cm visual analogue scale, duration of morning stiffness, and number of tender and swollen joints. Erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were measured at each visit. Antibodies to hepatitis B surface antigen (HBsAg) were determined by a commercial enzyme linked immunosorbent assay (ELISA) test kit. RESULTS: Hepatitis B vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease. The measures of disease activity of the patients and controls during the study period did not differ significantly: p=0.76 for daytime pain, p=0.1 for morning stiffness, p=0.24 and p=0.3 for tender and swollen joints respectively, p=0.08 for CRP, and p=0.12 for ESR. Fifteen of the 22 patients responded to vaccination, with an antibody level against HBsAg of 10 IU/l after seven months. Lack of response was associated with older age and higher scores of daytime pain. CONCLUSIONS: Hepatitis B vaccination is safe in RA and produces antibodies in 68% of the patients.

Antibody Formation↗

Clinical significance of low titer anti-nuclear antibodies in early rheumatoid arthritis: implications on the presentation and long-term course of the disease.

The objective of this study was to evaluate the clinical significance of anti-nuclear antibodies (ANA) detected in the early stages of rheumatoid arthritis (RA), by a retrospective comparison of the clinical, laboratory, and therapeutic characteristics of patients with or without ANA. The files of 99 longstanding seropositive RA patients were reviewed. Data relating to demographics, medical history, family history, physical findings, extra-articular complications, laboratory tests, drugs [dosage, duration. efficacy, combinations, adverse effects (AEs)], intra-articular injections, and surgery were recorded. Patients with or without ANA at presentation of their disease were compared using chi-square and t-tests. Fifty-two ANA positive (group 1) and 47 ANA negative (group 2) patients were enrolled in the study. All were comparable in terms of their mean age, age at diagnosis, follow-up duration (approximately 10.5 years), and male:female (M:F) ratio. On admission, pain complaints were more pronounced in group 1 (P = 0.004 in the feet), but the physical findings did not differ. Deformities and nodules developed in similar numbers. Extra-articular complications were evenly distributed; vasculitis, however, was significantly more prevalent in ANA positive (10/52) than in ANA negative (2/47) patients. Thyroid disease was more common in group 2 (10/47 vs 3/52). Laboratory tests (presentation and maximal values) were similar, with the exception of higher anti-DNA (but within normal ranges) and gamma-globulin% in group 1. Group 1 used more drugs prior to diagnosis. Corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) were evenly used. Combination therapy, joint injections, and surgery were more prevalent in group 2. AEs to various DMARDs were more common in group 1. Although similar in many aspects, RA patients with ANA tend to present with more pain complaints, a higher risk of vasculitis and AEs relating to use of DMARDs, while those without ANA needed more aggressive therapeutic modalities.

Antibodies, Antinuclear↗

A pilot study of a long acting somatostatin analogue for the treatment of refractory rheumatoid arthritis.

OBJECTIVE: To evaluate the efficacy and safety of a long acting somatostatin analogue in a subset of patients with refractory rheumatoid arthritis (RA). METHODS: Ten patients with active, refractory RA, who had failed to respond to at least four disease modifying antirheumatic drugs (DMARDs), were treated with monthly intramuscular injections of 20 mg of a long acting preparation of octreotide (Sandostatin-LAR) for three months. They were evaluated every two weeks in an open label pilot study. The primary measure of clinical response was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR 20). RESULTS: Eight patients completed the 14 week trial, while two patients received only one or two doses of the somatostatin analogue, but were eligible for evaluation. On an intention to treat basis 6/10 patients responded: four patients met the ACR 20 criteria at weeks 6-10, while two patients continued to improve with time, and met the ACR 50 and 70 criteria respectively, at week 14. On evaluation of the 10 patients as a group, a significant improvement (p<0.05) was noted in the mean visual analogue scales of pain, doctor's and patient's global assessment of disease activity, and in the mean number of swollen joints. Adverse effects were minor: transient bloating and loose stools, an urticarial rash (n=1), and a transient increase of liver enzymes (n=1). CONCLUSION: Treatment with a long acting somatostatin analogue led to significant clinical improvement in a subset of patients with active, refractory RA. The treatment was relatively safe and well tolerated. Further large, placebo controlled studies are required to evaluate this drug as a potential DMARD for patients with RA.

Adult↗

Psoriatic arthritis: interrelationships between skin and joint manifestations related to onset, course and distribution.

To assess the relationships between skin and joint disease, 70 patients with psoriatic arthritis were consecutively evaluated. Data were obtained regarding age, sex, duration of disease, age at onset, and flares of both skin and joint disease. Rheumatological assessment included morning stiffness, number of swollen, tender and deformed joints, involvement of distal interphalangeal joints (DIP), presence of dactylitis, Achilles tendinitis, and clinical lumbar and cervical involvement. Skin assessment included recording of the distribution of skin lesions and nail involvement, and grading of psoriasis severity using the PASI. The scalp was the most frequently involved site. Significant correlation was found between the PASI score and the number of deformed joints and Schober's test. The scalp score was found to correlate with the number of swollen joints, deformed joints, sausage finger and DIP involvement. Synchronous flares of skin and joint were significantly more frequent in the patients with onset of skin and joint diseases within the same year. Likewise, these patients showed a highly significant association between the PASI score and the number of tender, swollen and deformed joints, Schober's test and cervical involvement, whereas no such associations were found among patients with separate onset of skin and joint diseases.

Adolescent↗

Immediate and delayed effects of treatment at the Dead Sea in patients with psoriatic arthritis.

The purpose of this study was to evaluate the immediate and delayed effects of balneotherapy at the Dead Sea on patients with psoriatic arthritis (PsA). A total of 42 patients with PsA were treated at the Dead Sea for 4 weeks. Patients were randomly allocated into two groups: group 1 (23 patients) and group 2 (19 patients). Both groups received daily exposure to sun ultraviolet rays and regular bathing at the Dead Sea. Group 1 was also treated with mud packs and sulfur baths. Patients were assessed by a dermatologist and a rheumatologist 3 days before arrival, at the end of treatment, and at weeks 8, 16, and 28 from the start of treatment. The clinical indices assessed were morning stiffness, right and left hand grip, number of tender joints, number of swollen joints, Schober test, distance from finger to floor when bending forward, patient's self-assessment of disease severity, inflammatory neck and back pain and psoriasis area and severity index (PASI) score. Comparison between groups disclosed a similar statistically significant improvement for variables such as PASI, morning stiffness, patient self-assessment, right and left grip, Schober test and distance from finger to floor when bending forward. For variables such as tender and swollen joints, and inflammatory neck and back pain, improvement over time was statistically significant in group 1. Addition of mud packs and sulfur baths to sun ultraviolet exposure and Dead Sea baths seems to prolong beneficial effects and improves inflammatory back pain.

Arthritis, Psoriatic↗

Serum levels of IL-10, IL-6, IL-1ra, and sIL-2R in patients with psoriatic arthritis.

Our objective was to evaluate the levels of interleukin-6 (IL-6), soluble receptors of IL-2 (sIL-2R), IL-10, and IL-1 receptor antagonists (IL-1ra) in the serum of patients with psoriatic arthritis (PsA) and to assess the correlation between these levels and parameters of clinical activity of skin and joint disease. In total, 34 patients with PsA and ten healthy volunteers participated in the study. Assessment of joint disease included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory spinal back pain, and Schober test. Current severity of skin disease was graded according to the psoriasis area and severity index (PASI). Erythrocyte sedimentation rate (ESR) was determined as a marker of disease activity. Serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were measured by an enzyme immunoassay kit. Significantly higher serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were found in patients with PsA in comparison with healthy volunteers. A statistically significant correlation was found between levels of sIL-2R and PASI, whereas no association was found with clinical parameters of joint severity. Levels of IL-lra correlated with the number of tender and swollen joints. No correlation was found between levels of IL-6, IL-10, and clinical parameters of skin and joint severity. In the group of patients with PsA, serum levels of sIL-2R clearly correlated with severity of skin disease, whereas levels of IL-1ra were associated with joint severity.

Adult↗

Serum levels of hyaluronic acid in patients with psoriatic arthritis.

The purpose of this study was to evaluate the serum levels of hyaluronic acid (HA) in a group of patients with psoriatic arthritis (PsA), with special emphasis on the relationships between HA levels and clinical parameters of joint and skin activity. Thirty-four patients with PsA, 34 patients with rheumatoid arthritis (RA) and 49 healthy volunteers participated in the study. Assessment of joint disease in patients with PsA included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory back pain and Schober's test. The current severity of skin involvement was graded according to the Psoriasis Area Severity Index (PASI). Serum levels of HA were measured by a radiometric assay. The mean HA serum levels of patients with PsA and RA were significantly increased in comparison with healthy controls (107 +/- 39.6 microg/dl in patients with PsA, whereas in patients with RA it was 168 +/- 32.4 microg/dl and 36.7 +/- 5.5 microg/dl in healthy controls). A highly significant correlation was found between levels of HA and index of skin involvement, but no association was found between HA levels and clinical parameters of joint severity. We conclude that in this cohort of patients with PsA, HA levels clearly reflected psoriatic skin involvement although it did not correlate with joint disease.

Adult↗

INFLAMET: an image analyzer to display erythrocyte adhesiveness/aggregation.

Background: Due to a lack of simple, inexpensive, and real-time methodology, the state of erythrocyte adhesiveness/aggregation is not measured in daily practice by most clinicians. Methods: We measured the state of erythrocyte adhesiveness/aggregation before and following the administration of intravenous high-dose gamma globulins in 18 patients with various autoimmune diseases using a simple slide test and image analysis system (INFLAMET). Results: A significant (P=0.01) increment in the state of erythrocyte adhesiveness/aggregation (from 2+/-3 to 8+/-9 arbitrary units) was noted in the entire study group despite a significant (P=0.008) decrement (from 350+/-97 to 323+/-127 mg%) in the concentration of fibrinogen and no significant change in the erythrocyte sedimentation rate (32+/-30 mm/h before and 35+/-29 mm/h following administration of gamma globulin). Conclusions: By using a simple slide test and image analysis, we were able to provide relevant rheological information that was not available from either of the routine indirect tests, i.e. the Westergren erythrocyte sedimentation rate and the concentration of fibrinogen.

Journal Article↗