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M Yaron

Publications and source records attributed to M Yaron.

At least 55 records · Page 3Linked to original sources

Anti-interleukin-1 effects of diacerein and rhein in human osteoarthritic synovial tissue and cartilage cultures.

OBJECTIVE: The etiology of osteoarthritis (OA) is still a matter of debate. Several factors are known to be involved in the destruction of the articular cartilage. Interleukin-1 (IL-1) plays an important role in the pathogenesis of osteoarthritis (OA) either directly or through the stimulation of catabolic factors, such as nitric oxide (NO). The objective of this study was to evaluate the effect of diacerein, a new anti-OA agent and its active metabolite, rhein, on the production and function of IL-1beta, nitric oxide (NO) and receptor agonist (IL-1ra) in human OA cartilage and synovial tissue cultures. DESIGN: Synovial tissue and cartilage derived from OA patients were kept in culture for 48-72 hours in the presence of 1 microg/ml of lipopolysaccharide (LPS) with or without diacerein (10(-7)-10(-5) M), rhein (10(-7)-10(-5) M) and hydrocortisone (5 microg/ml). IL-1beta, IL-1ra, NO productions and 35S uptake were measured in culture media. In some experiments the resulting supernatants from synovial tissue cultures were added to cartilage. RESULTS: Diacerein and rhein, as well as hydrocortisone, significantly inhibited LPS-induced IL-1beta production by synovial tissue and cartilage. They also significantly reversed the inhibitory effect of LPS on cartilage 35S uptake. Culture media from synovial tissue containing LPS+diacerein (10(-6) M) or +rhein (10(-6) M) had a significantly less inhibitory effect on cartilage synthesis than culture media containing LPS only. Diacerein and rhein decreased NO release in synovial tissue and cartilage media and increased IL-1ra levels in cartilage culture media. CONCLUSION: An inhibitory effect of diacerein and rhein at therapeutic concentrations on both IL-1beta secretion and function in human synovial tissue and cartilage is suggested. Diacerein and rhein effects on NO production by LPS-stimulated OA synovial tissue and cartilage may both contribute and elucidate their anti-OA properties.

Aged↗

Hydroxychloroquine treatment for primary Sjögren's syndrome: its effect on salivary and serum inflammatory markers.

OBJECTIVE: To evaluate the effect of hydroxychloroquine treatment on interleukin 6 (IL6), hyaluronic acid (HA), and soluble interleukin 2 receptor (sIL2R) concentrations in the saliva and serum of patients with primary Sjögren's syndrome (SS). METHODS: Fourteen SS patients treated with hydroxychloroquine 200 mg/day for 12 months were investigated in an open prospective study. Clinical parameters of efficacy and routine biochemical and haematological data to assess drug safety and tolerability were determined every three months. Salivary and serum IL6, sIL2R, and HA values were determined at study entry, 6 and 12 months, using ELISA and radiometric assays. RESULTS: After hydroxychloroquine treatment, salivary IL6 concentrations decreased from 13.2 (1.2) to 7.3 (1.1) pg/ml (mean (SEM)) (p < 0.0001). Similarly, salivary HA concentrations were also reduced from 577.8 (120) to 200 (34) ng/ml (mean (SEM) (p < 0.003). Serum IL6 concentrations decreased from 5.4 (0.6) to 2.9 (0.2) pg/ml (mean (SEM) (p < 0.001), while serum HA concentrations remained unchanged. No change has been detected in salivary or serum sIL2R concentrations after 12 months of treatment with hydroxychloroquine. Treatment also resulted in significant reduction in erythrocyte sedimentation rate, serum gamma globulin, and C reactive protein values while only partial clinical improvement was noted in some patients. A more pronounced decrease of salivary IL6 and HA levels was found in the two patients in whom a reduction in the swelling of the parotid gland was noted. CONCLUSION: In this open label study of hydroxychloroquine treatment for SS a significant reduction of some salivary inflammatory markers was seen at the end of 12 months. Although during the treatment period only a partial clinical effect could be noted, the findings suggest that a double blind controlled study of hydroxychloroquine in SS is indicated.

Antirheumatic Agents↗

Avalanche deaths in the United States: a 45-year analysis.

OBJECTIVE: To describe the demographic characteristics and patterns of death of persons killed in snow avalanches over a 45-year study period. METHODS: The national avalanche database was the source of data in this retrospective, descriptive study. RESULTS: A total of 440 victims were killed in 324 fatal avalanches, of which 87.7% were fully buried, 4.7% were partially buried, and 7.6% were not buried. The average age was 27.6 +/- 10.6 years, and 87.3% were men. Victims who died included climbers (25.5%), backcountry skiers (22.7%), out-of-bounds skiers (10.0%), snowmobilers (6.8%), in-bounds skiers (5.2%), residents (4.5%), ski patrollers (3.6%), workers (3.6%), and motorists (3.0%). Over the 45-year study period there appear to be decreases in the deaths of in-bounds skiers, highway workers, and motorists. Increasing fatalities were observed among out-of-bounds skiers, snowmobilers, ski patrollers, and backcountry skiers. Most deaths occurred in Colorado (33.0%), Washington (13.2%), and Alaska (12.0%). CONCLUSIONS: Avalanche fatalities have increased over the last 45 years. Climbers, backcountry skiers, out-of-bounds skiers, and more recently snowmobilers constitute the majority of the victims. The decrease in deaths among groups that benefit from avalanche control programs supports the benefit of avalanche prevention strategies. Further study is needed to assess the impact of avalanche safety education for individuals who travel in remote and uncontrolled terrain.

Adolescent↗

The diagnosis of acute mountain sickness in preverbal children.

OBJECTIVE: To establish diagnostic criteria for acute mountain sickness (AMS) in preverbal children. DESIGN: Nonrandomized control trial. SETTING: Ambulatory. PARTICIPANTS: Children aged 3 through 36 months and adults from the Denver, Colo, area (altitude, 1610 m). MAIN OUTCOME MEASURES: The Lake Louise Scoring System was modified, using a fussiness score as the headache equivalent and a pediatric symptom score to assess appetite, vomiting, playfulness, and ability to sleep. Acute mountain sickness was assessed by combining the fussiness and pediatric symptom scores to produce what we termed the Children's Lake Louise AMS Score (CLLS). INTERVENTIONS: Parents recorded the fussiness score at 11 AM, 1, 3, and 5 PM, and the pediatric symptom score at 3:00 PM each day. Each subject traveled twice, with 1 day considered a control. Days 1 and 2 were measurements at home; day 3 reflected travel without altitude change to 1615 m; and 1 week later, day 4 involved travel to 3488 m. On days 3 and 4 the accompanying adults completed the Lake Louise Scoring System. RESULTS: Twenty-three subjects (14 boys; mean+/-SD age, 20.7+/-9.0 months) participated. The mean CLLS demonstrated no differences on days 1, 2, or 3. On day 4, 5 subjects (21.7%) had AMS, established as a CLLS of 7 or higher, and these scores normalized 2 hours after descent. Forty-five adults participated and 9 (20%) had AMS. CONCLUSIONS: We define AMS in preverbal children as a CLLS of 7 or higher with a fussiness score of 4 or higher and a pediatric symptom score of 3 or higher, in the setting of recent altitude gain. The incidence of AMS in preverbal children (21.7%) was similar to that in adults (20%).

Acute Disease↗

The impact of hemiparalysis on the expression of osteoarthritis.

OBJECTIVE: Primary generalized osteoarthritis (OA), the most prevalent joint disease, is usually symmetric. Sporadic case reports mention decreased OA manifestations in limbs in which there are neurologic deficits, but no systematic research has been published. The aim of the present study was to examine these observations in a planned and controlled survey in a group of patients with OA. METHODS: Seventy-five geriatric patients with a history of stroke and hemiparalysis were studied clinically and radiographically (hand radiographs; graded according to a modified Altman method) for the presence and the degree of OA in the hands. Detailed clinical and radiologic scores were calculated for each hand. Demographic, occupational, and neurologic data were collected. Patients with other joint or neurologic conditions were excluded. A group of 55 elderly patients without stroke were similarly studied (controls). Scores in the paralyzed hand were compared with those in the nonparalyzed hand in the stroke patients and subgroups (by Student's paired t-test and Wilcoxon test). Scores in the dominant hands were compared with those in the nondominant hands in stroke patients and control subjects (by Student's paired t-test and Mann-Whitney test). Correlation between the degree of neurologic damage and OA asymmetry (Pearson's correlation coefficient) was also sought. RESULTS: Paralyzed hands showed significantly fewer OA changes than nonparalyzed hands, both clinically and radiologically. This trend, accentuated in patients with more severe paralysis, disappeared in those with mild residual paresis. Asymmetry of OA was more pronounced in patients with flaccid, compared with spastic, paralysis. The degree of paralysis and loss of muscle strength correlated with the degree of OA asymmetry. Women had significantly higher OA scores than men. In the control group, dominant hands had higher OA scores, but this finding was concealed among hemiparalyzed patients. Lifetime gross occupational load and present grip strength did not correlate with the degree of OA. CONCLUSION: In elderly patients, hemiparalysis reduces ipsilateral hand expression of OA, while OA is accentuated (or increased) in the dominant hand of patients without paralysis. This first systematic study confirms the findings of previous case reports and lends support to the role of biomechanical factors in the development of OA.

Aged↗

Clinical and immunological study of 7 patients with minocycline-induced autoimmune phenomena.

PURPOSE: Prolonged treatment with minocycline for acne vulgaris has been associated with the development of arthralgia, arthritis, and other autoimmune phenomena. We characterized the clinical, laboratory, and immunological profiles of seven patients with this syndrome. SUBJECTS AND METHODS: Clinically the patients were studied with special emphasis on prior minocycline treatment, presenting symptoms, physical findings, course, and outcome. Laboratory tests included fluorescent antinuclear and antineutrophil cytoplasmic (ANCA) antibodies, as well as antibodies to myeloperoxidase, bactericidal permeability increasing protein, elastase, cathepsin G, lactoferrin, cardiolipin, and histone. RESULTS: All 7 patients presented with polyarthritis or arthralgia, morning stiffness, and fever after 6 to 36 months of minocycline treatment. The skin was involved in five patients (three with livedo reticularis and two with subcutaneous nodules). Two patients had chronic active hepatitis. Increased titers of perinuclear ANCA (p-ANCA) were detected in all seven patients; five patients had fluorescent antinuclear antibodies, two had antihistone autoantibodies and one had anticardiolipin antibodies. Antigenic characterization of p-ANCA disclosed antibodies to bactericidal permeability increasing protein in one patient, to elastase in three patients, and to cathepsin G in five patients. Symptoms resolved in five patients upon discontinuation of minocycline; the other two patients were treated with corticosteroids and also achieved remissions. CONCLUSION: Minocycline-induced autoimmune syndrome is characterized by reversible polyarthralgia or arthritis, morning stiffness, fever, frequent skin involvement, occasional chronic active hepatitis, and increased titers of p-ANCA with various minor p-ANCA-related antigens.

Acne Vulgaris↗

Elevated tear interleukin-6 levels in patients with Sjögren syndrome.

OBJECTIVE: The purpose of the study was to investigate interleukin-6 (IL-6) levels in the tear fluid and sera of patients with Sjögren syndrome (SS). PARTICIPANTS: Twelve patients with primary SS and 12 normal control subjects participated. INTERVENTION: Tear fluid and sera were obtained from the study and the control groups. Evaluation of tear fluid and sera IL-6 levels was done by using a quantitative enzyme-linked immunosorbent assay kit. All assays were carried out blindly with respect to diagnosis. MAIN OUTCOME MEASURES: Tear fluid IL-6 levels were measured. RESULTS: The mean concentration (+/- standard error) of IL-6 in the tears of patients with SS was elevated significantly compared to that of normal control subjects (88.6+/-16.2 vs. 42.1+/-10.6 pg/ml; P < 0.05). No significant differences were noted in the serum IL-6 levels between the two groups. A significant correlation (r = 0.742, P = 0.006) was found between tear fluid IL-6 levels and the focus score of lip biopsy specimens in patients with SS. CONCLUSION: Tear fluid IL-6 levels may serve as an important marker for tear gland involvement in SS.

Biomarkers↗

Allergic disorders in primary Sjögren's syndrome.

Allergic disorders have been described in a variety of connective tissue disorders. Although an association between allergy and primary Sjögren's syndrome has been suggested, it has not been well documented. The purpose of this study was to analyze the prevalence of several types of allergic disorders in a cohort of primary Sjögren's syndrome patients. The presence of an allergic disorder was evaluated by a specific questionnaire in 65 randomly selected primary Sjögren's syndrome patients and was compared to control groups of 67 rheumatoid arthritis patients, 53 patients with rheumatoid arthritis and sicca symptoms, and 31 patients with osteoarthritis. At least one type of allergic manifestation was reported by 42 of the 65 Sjögren's syndrome patients (65%). This rate was significantly higher than each of the three control groups (p < 0.01). Only drug allergy and skin contact allergy were found to be more prevalent in Sjögren's syndrome patients than in the control groups (p< 0.05). Allergic reactions were more common in Sjögren's syndrome patients who were anti-Ro positive (p < 0.05). As drug and skin contact allergies are a frequent finding in Sjögren's syndrome patients, obtaining a careful history is needed before prescribing drugs in these patients.

Adult↗

Gut feeling.

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Appendectomy↗

Salivary and serum hyaluronic acid concentrations in patients with Sjögren's syndrome.

OBJECTIVE: To evaluate salivary hyaluronic acid (HA) concentration in patients with primary Sjögren's syndrome (SS). METHODS: Salivary and serum HA concentrations were evaluated using a radiometric assay. Thirty nine patients with SS served as the study group and their results were compared with 19 patients having clinical symptoms and signs of dry mouth and with 10 normal controls. RESULTS: Salivary HA concentrations were significantly increased (p < 0.05) in the 39 patients with SS compared with the 19 patients with dry mouth and the 10 normal controls (240.7 (38.5) v 99.8 (14.6) and 91.3 (7.9) ng/ml, respectively) (mean (SEM)). No significant differences were noted in the serum HA concentrations between the three groups (42 (3.9) v 36.3 (4.1) and 32 (4.3) ng/ml, respectively) (mean (SEM)). No correlation could be found between salivary HA concentrations and the focus score of lip biopsies, nor between salivary HA concentrations and erythrocyte sedimentation rate or other serological tests. CONCLUSION: Increased salivary HA concentrations can serve as a marker of local inflammation and may be of value in the diagnosis of SS.

Adult↗

Toxicity profile of dual methotrexate combinations with gold, hydroxychloroquine, sulphasalazine and minocycline in rheumatoid arthritis patients.

The purpose of the present study was to evaluate the toxicity and tolerability of methotrexate (MTX)/gold (G; group 1) combination therapy as compared to other MTX combinations [MTX with hydroxychloroquine (HCQ; group 2), MTX with sulphasalazine (SASP; group 3) and MTX with minocycline (MNC; group 4)]. The hospital records of 127 consecutive rheumatoid arthritis (RA) patients who were treated with these combinations during a period of 24 months were retrospectively reviewed. The toxicity and tolerability of the MTX/G combination was compared to the other dual MTX combinations and also to MTX alone using data previously reported by us on 126 RA patients treated with single MTX therapy. The mean exposure time to treatment was 16 months in group 1 and 13 months in the other dual MTX combinations. During the period of follow-up, the combination was stopped in 22 out of 42 patients in group 1 (52%) in comparison with 54 patients out of 86 patients (63%) in the other dual regimen groups. The discontinuation rate was highest in group 4 (due to side effects and lack of compliance) and this was statistically significant in comparison with group 1. The proportion of adverse events was lowest in group 1 (14%) and highest in groups 3 and 4 (25%). Side effects were reversible and comparable with those of MTX alone (23%). No fatal or life-threatening side effects were recorded during any of these MTX combination therapies. We concluded that the combinations of MTX with G, HCQ, SASP and MNC in RA were relatively well tolerated. No increase in toxicity compared with MTX alone was observed. The lowest rate of side effects was noted in group 1, while group 4 presented the highest discontinuation rate.

Adult↗

Anti-Ro (SSA) antibodies in rheumatoid arthritis patients with gold-induced side effects.

The purpose of our study was to investigate the significance of the presence of anti-Ro antibodies found by us in an earlier study of rheumatoid arthritis (RA) patients with gold-induced side effects. Sera of 29 anti-Ro (SSA) positive RA patients who had gold-induced side effects were studied. All sera were examined by Western blot using recombinant antigens, encoding the Ro 60 kD and the La proteins. HLA typing was done in all patients. Thirteen patients reacted only with the Ro 52 kD antigen and all had severe skin eruptions caused by gold therapy. Another ten patients who reacted only with the Ro 60 kD antigen had other side effects to gold (six had proteinuria and four leucopenia). Six patients who reacted to all three antigens (Ro 52 kD, Ro 60 kD and La) had secondary Sjögren's syndrome. No significant statistical differences were noted in the incidence of HLA-DR3 between the subgroups of patients. Our data indicated that antibodies to the Ro 52 kD antigen are associated with skin eruptions in RA patients treated with gold.

Aged↗

Saliva: an additional diagnostic tool in Sjögren's syndrome.

OBJECTIVE: To assess the available data and the place of salivary analysis in the diagnosis of Sjögren's syndrome (SS). METHODS: A Medline search of English language articles published between 1985 and 1996 and a manual search of the reference lists of relevant articles formed the data sources. These were combined with our clinical and experimental experience in this field. Each method of salivary analysis was assessed according to study design, type of saliva used for the study, sensitivity/ specificity for the diagnosis of SS, and correlation to the histopathological findings. RESULTS: Increased levels of salivary Na+, immunoglobulins (particularly IgA), anti-Ro and La antibodies, lactoferrin, lysozyme, beta 2 microglobulin, prostaglandin E2, thromboxane B2, interleukin-6, and hyaluronic acid have been detected in various studies. Results varied according to the different methods used for saliva collection. CONCLUSION: Although many changes have been detected in various constituents of saliva in SS patients, no test has proved sensitive or specific enough for diagnosing SS.

Autoantibodies↗