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Biomedical subjects

E Toubi

Publications and source records attributed to E Toubi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Immune aberrations in B and T lymphocytes derived from chronic urticaria patients.

To investigate the pathophysiology of chronic urticaria (CU) in light of the abundant evidences that it is an autoimmune disease and to define some cellular markers in B/T lymphocytes that could be of pathogenic significance, we investigated 14 patients suffering from CU, compared to 7 contact dermatitis patients and 10 normal control individuals. We tested the expression of CD5, B7.1 (CD80), CD23, and CD25 on B cells and of CD(40L)) and CD25 on T cells from all studied individuals. We also tested B cell proliferation upon their activation followed by dexamethazone induced inhibition of proliferation. The expression of bcl-2 protein in activated lymphocytes from normal individuals was compared to that of contact dermatitis and CU patients. CD(40L) expression was found significantly higher on in (vitro activated CD3 [with phorbol myristate acetate (PMA) and ionomycine Ca2+ at 12 hr of culture] from CU patients compared to that of contact dermatitis and normal individuals. Whereas the proliferation of activated B cells from CU patients was higher, dexamethazone-induced inhibition of B cell proliferation was found statistically similar in both groups yet lower in B cells from most severe CU patients. We demonstrate a higher bcl-2 expression in activated B and T lymphocytes of severe CU patients compared to that of moderate CU and both contact dermatitis and normal individuals. The increased expression of CD(40L) on activated T cells might play a role in the polyclonal increased B cell proliferation of CU patients. This increased proliferation accompanies the finding that activated B and T lymphocytes from these patients demonstrate increased bcl-2 expression. The resistance of some B cells to dexamethazone-induced inhibition of proliferation encourages us to investigate the possibility that B cells from some CU patients might develop rescue mechanisms from activated cell death. These findings provide further evidence that CU is indeed an autoimmune disease, although its precise nature has yet to be fully elucidated.

Adult↗
PubMed2000

The benefit of combining hydroxychloroquine with quinacrine in the treatment of SLE patients.

BACKGROUND: Although the benefit of antimalarials in the treatment of cutaneous LE is well established, the effect of combined hydroxychloroquine and quinacrine treatment in systemic lupus erythematosus with major organ involvement remains underappreciated. PATIENTS: Six active SLE patients (SLEDAI score > 5 points), with a mean duration of illness 9.1 yr (range 2-17 yr) were started on quinacrine (100 mg/d) following failure to achieve clinical remission on a therapeutic regimen which included a maintenance dose of hydroxychloroquine (400 mg/d) together with prednisone (either 10-20 mg/d or higher daily doses of this agent for short periods) and azathioprine (150 mg/d) or methotrexate (7.5 mg/week). OUTCOME: In 5/6 of the patients the addition of quinacrine to the previous treatment resulted in complete remission (SLEDAI 0-2 points), which persisted over the follow-up period [mean +/- 2.2 yr (range 0.5-3.5)]. During this period hydroxychloroquine and azathioprine were reduced to 200 mg/d and 100 mg/d respectively, whereas prednisone was modified as follows: in 2 patients daily administration was discontinued; in one the dose was reduced to 2.5 mg/d (from that of > or = 20 mg/d); in 2 others the previous need for an intermittent course was avoided. However, in one out of the six patients the addition for 3 months of quinacrine to the therapeutic protocol did not result in clinical improvement and was therefore discontinued. CONCLUSIONS: The promising results of this preliminary investigation encourages the combined use of the two antimalarial drugs in appropriate candidates. This modality may induce remission, seems to be safe and possesses a steroid sparing effect.

Adult↗
PubMed2000

Use of antikeratin antibodies to distinguish between rheumatoid arthritis and polyarthritis associated with hepatitis C infection.

OBJECTIVE: To investigate whether antikeratin antibodies (AKA) could be useful in the differential diagnosis of patients with rheumatoid arthritis (RA) compared to patients with hepatitis C virus (HCV) associated polyarthritis, who are seropositive for rheumatoid factor (RF). METHODS: AKA were assayed in 3 different groups of patients; all were RF seropositive: Group 1: 25 patients with HCV associated polyarthralgia or arthritis. Group 2: 33 patients with RA. Group 3: 13 patients with autoimmune disorders other than RA. Fifteen healthy individuals served as controls. RESULTS: AKA were detected in 20/33 patients with RA (60.6%) compared to only 2/25 patients (8%) with HCV associated arthritis (p < 0.0001). AKA were observed in 2/13 patients of Group 3 (15.3%). These results were also statistically different from those of patients with RA (p = 0.008). AKA were not found in the sera of the healthy controls. CONCLUSION: AKA is a useful marker to differentiate patients with RA from those with hepatitis C arthritis.

Adult↗
PubMed2000

Treatment of refractory, symptomatic, hepatitis C virus related mixed cryoglobulinemia with ribavirin and interferon-alpha.

OBJECTIVE: To assess the benefit of interferon-alpha/ribavirin combination therapy in hepatitis C virus (HCV) infected patients with symptomatic mixed cryoglobulinemia (MC) who failed to respond to treatment with interferon-alpha (IFN-alpha). METHODS: Nine patients (mean age 57 +/- 14 yrs) with type II symptomatic MC who failed to respond to IFN-alpha monotherapy were re-treated with combination treatment of IFN-alpha 3 times weekly and ribavirin 15 mg/kg daily for 6 months. Five of 9 patients had previously received additional treatment during IFN-alpha monotherapy. Clinical and laboratory evaluations (including cryocrit level) were performed weekly for the first month and monthly thereafter. RESULTS: Baseline mean alanine aminotransferase (ALT) and cryocrit levels were 119 +/- 97 IU/l and 7.9% +/- 10%, respectively. All patients were HCV-RNA positive and 5 had cirrhosis. At the end of therapy, mean ALT level was 84 +/- 79 IU/l (p = 0.02), while normal ALT levels were observed in 4 of 9 patients (44%). However, complete virological response was achieved in only 2 patients (22%). Cryoglobulin became undetectable within 6 weeks of therapy in 7 patients (78%) and decreased significantly in 2 others (p = 0.008). A substantial improvement in MC related symptoms (arthralgia/arthritis, proteinuria, skin vasculitis) was achieved in all patients within 10 weeks of combination therapy, although polyneuropathy related symptoms were relatively resistant to treatment. CONCLUSION: Symptomatic, refractory HCV related MC should be considered as an indication for combination therapy with IFN-alpha and ribavirin. Improvement in MC related symptoms can be achieved even without complete biochemical or virological response.

Adult↗
PubMed1999

The spectrum of apoptotic defects and clinical manifestations, including systemic lupus erythematosus, in humans with CD95 (Fas/APO-1) mutations.

OBJECTIVE: To determine the clinical spectrum of disease in humans with mutations in the CD95 (Fas/ APO-1) receptor and to obtain mechanistic insight into the different clinical phenotypes observed. METHODS: Clinical information for each of the index cases, first-degree relatives, and any family members reported to have Canale-Smith syndrome (or another autoimmune disease) was gathered by direct interview, chart review, and verification of data by the physician or pathologist concerned. Apoptosis of activated T or B lymphocytes was induced by agonistic anti-CD95 antibodies and quantified by a cell death assay (propidium iodide staining in the subdiploid peak) or cell viability assay (alamar blue or 3H-thymidine incorporation). RESULTS: Evaluation of an additional 8 probands with novel heterozygous CD95 mutations revealed hypergammaglobulinemia and immune-mediated cytopenias in all patients, as well as urticarial rash, oral ulceration, lymphopenia, and peripheral neuropathy in some individuals. One patient (P4) had systemic lupus erythematosus (SLE) characterized by a World Health Organization class V lupus nephropathy, a recurrent, reversible multifocal central nervous system disorder, high-titer antiphospholipid autoantibodies, and autoimmune cytopenias. In the P4 pedigree, the father had reduced T and B cell apoptosis associated with a CD95 mutation, whereas an independent B cell apoptotic defect was demonstrated in maternal family members who did not have a CD95 mutation. Three cases of B cell lymphoma occurred in carriers of the CD95 mutation. CONCLUSIONS: CD95 mutations are associated with loss of regulation of B lymphocytes, which predisposes to systemic autoimmunity including SLE. The P4 family provides a model of the complex genetic and functional interactions that are required for the development of a lupus-like syndrome.

Apoptosis↗
PubMed1999

Follow-up after systemic adverse reactions of immunotherapy.

Out of 280 immunotherapy (IT)-treated patients in our allergy clinic, 37 (13%) developed systemic adverse reactions. Parietaria judaica (Pj) extract, a highly allergenic pollen in northern Israel, was part of the IT regimen in 46% of treated patients who developed systemic adverse reactions. Twenty-six (70%) of systemic adverse reactions occurred during the buildup phase, whereas 11 (30%) occurred in the maintenance phase of treatment. Mild systemic reactions developed in 15/37 (40%), moderate in 20/37 (54%), and severe in 2/37 (5%) of patients. In 22/37 (59% of our IT-treated patients, adverse reactions developed within 30 min after injection. Among these were the two patients with severe systemic reactions. In 19%, moderate adverse reactions appeared at 30-60 min; in 22%, mild to moderate reactions appeared after 1-2 h. Our study concludes that severe systemic reactions to IT usually appear within 30 min after injection. In Israel, IT with highly allergenic pollens such as Pj frequently causes systemic reactions, even during the maintenance phase of treatment. In such cases, the reduction of IT dosage should be more than 50% during the pollen season, and a waiting period of 1 h should also be considered.

Allergens↗
PubMed1997

Low-dose cyclosporin A in the treatment of severe chronic idiopathic urticaria.

In a limited number of severe chronic idiopathic urticaria (CIU) patients, low-dose cyclosporin A (CsA) treatment was found to be effective. This open study aimed to extend this clinical observation and determine the safety of treatment with CsA. In addition, it aimed to determine the prevalence and characteristics of the autologous serum skin test (AST) in such patients, and whether this test is affected by CsA treatment. Thirty-five patients who suffered from severe CIU (score 3), and who were followed for 6 months (using a clinical urticaria-severity score [range 0-3]) were divided into three groups: 19/35 were treated for 3 months with low-dose CsA, and thereafter followed for an additional 3 months; 6/35 dropped out of protocol treatment; and 10/35 untreated patients (followed for the same period) served as a disease controls. In the treated group, no side-effects were observed, and by the end of treatment, 13/19 (68%) patients were in full remission (score 0) and the remainder scored 1. In contrast, the 10 CsA-untreated patients scored 3 for the whole follow-up period of 6 months. Positive AST was found in 14/35 (40%) of patients, whereas none were detected in 20 healty control subjects. AST neither correlated with disease activity nor predicted response to treatment. This uncontrolled study shows that low-dose CsA is effective in treating CIU patients, and can be given safely for 3 months. However, CIU patients requiring initially high doses of glucocorticosteroids and with a long clinical history are less amenable to CsA treatment.

Adult↗
PubMed1997

Severe reversible cardiomyopathy associated with systemic vasculitis in primary Sjögren's syndrome.

A 40y old woman with primary Sjögren's syndrome developed elevated purpura, peripheral neuropathy, muscular tenderness, abdominal pain, heart failure, and convulsive spells. The hallmarks of this disease were high titers of anti-Ro antibodies and low complement levels in the serum, leukocytoclastic small vessel vasculitis in the cutaneous biopsy specimen, and a life threatening clinical course. Echocardiography revealed left ventricular hypokinesis with low ejection fraction, which is unlike the more common features of cardiomyopathy complicating Sjögren's syndrome. The rapidly deteriorating heart failure and other systemic complications remitted on pulse corticosteroid and cyclophosphamide therapy. The pathogenesis of heart failure, which appeared concurrently with vasculitis and was reversed on immunosuppressive therapy, is explained in the context of the systemic disease. Leukocytoclastic vasculitis might be at the origin of this rare variant of acute, severe but reversible cardiomyopathy in pSS.

Adult↗
PubMed1997

Autoimmune aberration in sudden sensorineural hearing loss: association with anti-cardiolipin antibodies.

In view of the presence of autoantibodies against inner ear antigens, the pathogenesis of sudden deafness (SD) and progressive sensorineural hearing loss (PSNHL) is suggested to be of an autoimmune nature. However, microthrombosis of the inner ear may result from pathogenic anti-cardiolipin antibody (aCL) activity. We studied 30 patients (17 females and 13 males, age range 20-52 y), of whom 11 suffered from SD and 19 from PSNHL. All were clinically and serologically evaluated for association with autoimmune disorders (serological examination included: aCL, ANA, ENA, ANCA, proteinelectrophoresis, and complement levels). Twenty healthy matched subjects served as controls. None of the control group were aCL positive, whereas 8 out of 30 (27%) patients demonstrated low-moderate titers (P < 0.02), of whom 5 out of 8 suffered from SD. In addition, 2 aCL negative patients with PSNHL demonstrated hypergammaglubolinemia accompanied by hypocomplementemia, whereas none with SD had such abnormalities. Our data suggests that aCL is detected in patients with sudden sensorineural hearing loss and therefore may play an important role in the pathogenesis of this disability. If sustained by additional studies, these findings would warrant the consideration of anticoagulant therapy.

Adult↗
PubMed1996

Anticardiolipin antibodies and acute myocardial infarction in non-systemic lupus erythmatosus patients: a controlled prospective study.

PURPOSE: To examine the prevalence of anticardiolipin antibodies (ACLA) in relatively young patients with acute myocardial infarction (MI) and their role in subsequent coronary and thromboembolic events in the post-MI period. PATIENTS AND METHODS: In 124 relatively young survivors (aged 65 or younger) of acute MI, ACLA were measured in a controlled prospective study on admission and 3 months later. Myocardial reinfarction and thromboembolic events during a mean follow-up period of 19 +/- 3 months were diagnosed by standard tests. RESULTS: Seventeen (14%) of the 124 patients were ACLA positive (either IgM or IgG) upon admission compared with 2 out of 76 (3%) of the control group matched for age and coronary risk factors (P < 0.01). The levels of ACLA remained unchanged in all but 1 patient 3 months later. During the follow-up period the rate of thromboembolic events and myocardial reinfarction was significantly higher in the ACLA-positive patients as compared with the ACLA-negative group: 41% versus 4% (P < 0.0001) and 35% versus 10% (P < 0.05), respectively. Using logistic regression, high titer of ACLA was found to be the only independent risk factor for subsequent thromboembolic events or myocardial reinfarction after acute MI. CONCLUSIONS: High prevalence of ACLA was found in relatively young survivors of acute MI. The presence of ACLA is a marker for increased risk of subsequent myocardial reinfarction and thromboembolic events after acute MI.

Adult↗
PubMed1996

Hydroxychloroquine and lupus pregnancy: review of a series of 36 cases.

OBJECTIVE: To study maternal and fetal outcome of pregnancy in patients with lupus who were exposed to hydroxychloroquine (HCQ). METHODS: The case records of women (n = 33) exposed to HCQ during their pregnancies (n = 36) and of 53 control patients from a single lupus pregnancy centre were reviewed to determine lupus activity, obstetric experience, and infant outcome. RESULTS: HCQ was not apparently teratogenic. Lupus activity and obstetric outcome in the two groups were similar. CONCLUSION: HCQ continuation is probably safe during pregnancy in patients with lupus, but there is no obvious advantage in commencing treatment.

Adult↗