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Biomedical subjects

D Caspi

Publications and source records attributed to D Caspi.

At least 37 records · Page 2Linked to original sources

Fluoxetine and amitriptyline inhibit nitric oxide, prostaglandin E2, and hyaluronic acid production in human synovial cells and synovial tissue cultures.

OBJECTIVE: To evaluate the effects of fluoxetine and amitriptyline on nitric oxide (NO), prostaglandin E2 (PGE2), and hyaluronic acid (HA) production in human synovial cells and synovial tissue cultures. METHODS: Human synovial cells, synovial tissue, and cartilage were cultured in the presence or absence of cytokines, lipopolysaccharides (LPS), fluoxetine, or amitriptyline. Production of NO, PGE2, and HA was determined in culture media. Sulfated glycosaminoglycan (S-GAG) synthesis was evaluated in cartilage by 35S incorporation. RESULTS: Fluoxetine (0.3 microg/ml, 1 microg/ml, and 3 microg/ml) inhibited NO release by 56%, 62%, and 71%, respectively, in the media of synovial cells stimulated by interleukin-1alpha (IL-1alpha; 1 ng/ml) plus tumor necrosis factor alpha (TNFalpha; 30 ng/ml). Amitriptyline (0.3 microg/ml, 1 microg/ml, and 3 microg/ml) caused a 16%, 27.3%, and 51.4% inhibition of NO release. Fluoxetine and amitriptyline (0.3 microg/ml, 1 microg/ml, and 3 microg/ml) significantly (P<0.05) inhibited PGE2 release in the media of human synovial cells in the presence of IL-1alpha plus TNFalpha, in a dose-dependent manner (up to 88% inhibition). Fluoxetine (0.3 microg/ml, 1 microg/ml, and 3 microg/ml) and amitriptyline (1 microg/ml and 3 microg/ml) significantly (P<0.05) inhibited PGE2 release in the media of human synovial tissue in the presence of LPS. Fluoxetine and amitriptyline (0.3 microg/ml, 1 microg/ml, and 3 microg/ml) also significantly (P<0.05) inhibited HA production by human synovial cells in the presence of IL-1beta plus TNFalpha. Fluoxetine and amitriptyline (1 microg/ml) partially reversed IL-1beta-induced inhibition of 35S-GAG synthesis by human cartilage cultures (P<0.05). Neither fluoxetine nor amitriptyline had a toxic effect on cells in the concentrations used. CONCLUSION: Inhibition of NO and PGE2 production by connective tissue cells is a mechanism by which some antidepressant medications may affect pain, articular inflammation, and joint damage.

Aged↗

Minocycline-induced autoimmune syndromes: an overview.

OBJECTIVE: To increase awareness of minocycline-induced autoimmune syndromes. METHODS: Review of relevant publications from the American and European literature. RESULTS: Four minocycline-induced syndromes have been described in 82 patients: serum sickness, drug-induced lupus, autoimmune hepatitis, and vasculitis. Aside from sporadic cases of serum sickness, all other syndromes occurred in patients treated for acne. Drug-induced lupus and hepatitis were by far the most common events (66 cases). Except for serum sickness, which presented shortly (mean, 16 days) after minocycline, the autoimmune syndromes manifested after protracted use (mean, 25.3 months). As expected, the patients with acne were young (mean, 19.7 years). The most frequent symptoms were arthralgia, followed by arthritis, fever, and rash (73, 45, 38, and 29 patients, respectively). Serologically, antinuclear antibodies were the most common finding (63 positive of 68 tests); perinuclear anti-neutrophilic cytoplasmic antibodies (pANCA), when assayed, were similarly frequent (20 of 24 tests). Surprisingly, anti-histone antibodies were uncommon, even among patients with drug-induced lupus (4 of 31 tests). The clinical and serological features of the separate syndromes may overlap. The diagnostic value of pANCA, as well as its possible role in minocycline-induced autoimmunity, are discussed. CONCLUSIONS: Minocycline has the potential to evoke a variety of clinical and serological autoimmune expressions. The number of published reports may underestimate the frequency of this condition, which should be suspected and investigated in young patients with autoimmune manifestations.

Anti-Bacterial Agents↗

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↗

Gut feeling.

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Appendectomy↗

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↗

Minocycline induced arthritis associated with fever, livedo reticularis, and pANCA.

OBJECTIVE: To describe a novel iatrogenic immunological reaction produced by minocycline. CASE REPORTS: The clinical course and laboratory results of three women who presented with similar rheumatological manifestations after a prolonged exposure to minocycline are described. All three presented a unique reaction manifested by fever, arthritis/arthralgia and livedo reticularis during treatment with minocycline for acne vulgaris. The clinical syndrome was associated with high titre of serum perinuclear anticytoplasmatic antibodies (p-ANCA) and antimyeloperoxidase antibody (anti-MPO). Symptoms resolved after stopping the drug and recurred promptly after rechallenge in all three patients. CONCLUSIONS: Minocycline, which is widely used in the treatment of acne, often without adequate supervision, may induce arthritis and livedo vasculitis associated with anti-MPO.

Acne Vulgaris↗

Long-term experience with low dose methotrexate in rheumatoid arthritis.

One hundred twenty-six patients with rheumatoid arthritis (RA) were treated with weekly low doses of methotrexate (MTX) for a mean period of 36.8 months (range 13-110 months). The overall probability of continuing with MTX therapy was 72% at 2 and 3 years, 67% at 4 years and 65% at 5-7 years. Seronegative patients had a higher probability of continuing therapy than seropositive patients (P < 0.05). Out of the whole group, 8% showed no improvement, 16% showed mild improvement, 30% showed moderate improvement, and 45% experienced marked improvement. Eight patients (6%) of the latter group achieved complete clinical remission. In the course of the follow-up period there was a significant decrease in the mean daily dosage of prednisone and NSAIDs. Minor side effects were common (68%), but therapy was discontinued in only 27 patients (21%) because of major complications. In most of them (25 out of 27) these occurred within the first 24 months of therapy. Although malignancy was revealed in 5 patients during the follow-up period, its occurrence did not differ from expected rates.

Aged↗

SAPHO syndrome.

Four women with pustulosis palmoplantaris (PPP) and associated sternocostoclavicular hyperostosis are described. The connection between the two diseases is not coincidental: it is encountered in 9.4% of PPP patients, and was reported in the French literature as part of the SAPHO (synovitis acne pustulosis hyperostosis osteomyelitis) syndrome. This syndrome is linked to the spondyloarthropathies, having an increased prevalence of HLA B27 and occurrence of sacroiliitis. None of our patients had HLA B27, but HLA A26 was found in the 3 patients examined. No conclusion can be drawn from this finding, however, since this antigen is found in 21.7% of Ashkenazi Jews. Recognition of this syndrome by dermatologists will improve diagnosis and treatment.

Acne Vulgaris↗

A prospective analysis of liver biopsies in rheumatoid arthritis patients receiving long term methotrexate therapy.

Baseline and sequential liver biopsies were performed in ten patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) for more than 4 years. Liver biopsies were performed in all patients before the initiation of MTX therapy and were repeated after reaching a cumulative dose of 1500 mg or more. In four patients a third biopsy was performed 3 years after the first one. No significant worsening of hepatic architecture was found in any of our patients after 4 to 7 1/2 years of MTX therapy. No correlations between histologic findings and various clinical or pharmacological variables could be found. Our results suggested that prolonged MTX administration in RA patients did not cause severe hepatic abnormalities.

Adult↗

Antibodies against crystals.

We suggest that crystals, when introduced into an organism, may behave as conventional antigens, mediating the production of specific antibodies. These antibodies would bear an imprint of the crystal surface and may consequently behave as a nucleating matrix in a new crystallization event. Thus, they would behave as catalytic antibodies. We show that IgG antibodies isolated from patients suffering from gout, a joint disease caused by crystals of monosodium urate monohydrate (MSUM), accelerate the appearance of new crystals of MSUM from a supersaturated solution of the salt in vitro. The same effect is not observed for IgG antibodies isolated from the joint fluids of patients with other joint diseases, such as pseudogout, rheumatoid arthritis, or osteoarthritis. Furthermore, IgG antibodies obtained from rabbits injected subcutaneously with crystals of MSUM, were also nucleating towards MSUM crystals.

Allopurinol↗

Methotrexate treatment of rheumatoid arthritis: is a fortnightly maintenance schedule enough?

In 15 patients with rheumatoid arthritis who were in clinical remission the weekly regimen of methotrexate treatment was changed to fortnightly without a change in dose. A total of 13 patients completed a 12 month trial. No change in clinical or laboratory parameters occurred. There was no change in the use of analgesics or non-steroidal anti-inflammatory drugs and the patients remained in remission. Two patients had to be withdrawn after two and four months respectively because of a flare in disease activity. It is suggested that in most patients with rheumatoid arthritis who are treated with methotrexate and whose disease activity is stable a fortnightly regimen can be permitted without affecting drug efficacy.

Arthritis, Rheumatoid↗