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Y Molad

Publications and source records attributed to Y Molad.

At least 19 recordsLinked to original sources
PubMed2005

Maternal and fetal outcome of lupus pregnancy: a prospective study of 29 pregnancies.

The aim of this study was to analyse pregestational and pregnancy risk factors for adverse fetal and maternal outcome in lupus pregnancy. Twenty women with systemic lupus erythematosus (SLE) (29 pregnancies) were prospectively evaluated. Mean patient age was 29.5+/-4.7 years, and mean disease duration, 6.3+/-6.5 years. Twenty-two pregnancies (75.9%) ended in live births; preterm delivery occurred in 17.4%, intrauterine growth restriction in 50%, preeclampsia in 3.7%, and gestational hypertension in 8%. Six pregnancies (20.7%) ended in spontaneous abortions. Adverse live-birth outcome was significantly associated with low pregestational serum albumin level, elevated gestational anti-dsDNA antibody, and diabetes mellitus. Spontaneous abortion was directly associated with low levels of pregestational serum albumin, positive anticardiolipin IgA, anti-beta2-glycoprotein I IgM, and anti-La antibodies, and inversely associated with number of patients' children. Postgestational lupus flare-up was noted in six pregnancies. Risk factors included high pregestational SLE Disease Activity Index (SLEDAI), lower serum albumin, elevated serum antibody to dsDNA, proteinuria, and use of prednisone and hydroxychloroquine. We conclude that despite high rate of obstetrical complications and postpartum lupus flare-up, pregnancy poses low risk for the majority of women with SLE.

Adult↗
PubMed2003

Primary anetoderma: a cutaneous sign of antiphospholipid antibodies.

Although a few reports in recent years have suggested that patients with antiphospholipid antibodies (aPL) are prone to developing primary anetoderma (PA), it is still unclear how often aPL are detected in unselected PA patients. We studied nine consecutive PA patients for the presence of autoimmune antibodies and disorders in general and the presence of aPL in particular. Six of the nine patients had clinical evidence of associated autoimmune disorders (Graves'disease and autoimmune haemolysis in one, systemic scleroderma in one, Hashimoto's thyroiditis in one, alopecia areata in one) and/or signs of hypercoagulability (recurrent fetal loss in two, recurrent stokes in one, recurrent deep vein thrombosis in one). In four ofthese six patients the onset of PA preceded these signs. Positive aPL was found in all: anticardiolipin (aCL) in six, anti-beta2-glycoprotein-I (a(beta)2GPI) in six and lupus anticoagulant (LAC) in four. The most frequent isotype was IgA. Among other autoantibodies found the most frequently was antinuclear antibodies. Four ofthe nine patients fulfilled the criteria for antiphospholipid syndrome (APS). It is concluded that PA is an important cutaneous sign for autoimmune disorders in general and the presence of aPL in particular. Hence, the work-up of these patients should include testing for LAC as well as for all different isotypes ofaCL and a(beta)2GPI. We recommend that PA be added to the list of the cutaneous manifestations of APS.

Adult↗
PubMed2002

Protective effect of hydroxychloroquine in systemic lupus erythematosus. Prospective long-term study of an Israeli cohort.

Systemic lupus erythematosus-associated irreversible organ/system damage was previously associated with various clinical and demographic features. We analysed the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) in a cohort of 151 Israeli patients followed for a mean (+/- s.d.) period of 45.7 +/- 37.4 months. Mean score of SLICC/ACR DI at the first and last encounters were 0.17 +/- 64 and 1.64 +/- 2.1, respectively (P < 0.0001). Multiple logistic regression analyses disclosed a statistically significant positive correlation with corticosteroid and cyclophosphamide therapy. Hydroxychloroquine therapy was significantly associated with lower SLICC/ACR DI. Although the size of our study group did not allow us to find specific organs/systems which were associated with the protective effect of hydroxychloroquine, we suggest this is due to the antiatherogenic effects attributed to antimalarial therapy in SLE.

Adolescent↗
PubMed2001

Allelic distribution of HLA-B*5 in HLA-B5-positive Israeli patients with Behçet's disease.

In order to investigate the sub-typing of the B5 antigen in Israeli (Jewish and Arabic) patients with Behçet's disease (BD) allele-specific genotyping of B51 and B52 alleles was performed in Israeli BD patients and healthy controls. Among the HLA-B51-positive BD patients, B*5101 was found to be the predominant allele, identified in 62% of all BD patients and 78% of Jewish BD patients. HLA-B*5101 was also the predominant allele in HLA-B51-positive healthy controls. HLA-B*5108 and B*5104 alleles were identified in 23% and 15% of B51-positive BD patients, respectively. The HLA-B*5201 allele was identified in all HLA-B52-positive patients and controls. Our study suggests that both HLA-B*5101 and HLA-B*5201 are the dominant alleles of HLA-B5 in Israeli BD patients.

Alleles↗
PubMed2000

Renal outcome and vascular morbidity in systemic lupus erythematosus (SLE): lack of association with the angiotensin-converting enzyme gene polymorphism.

OBJECTIVES: The angiotensin-converting enzyme (ACE) gene polymorphism has been associated with worse outcome in various chronic glomerular disorders and in hypertension. Because nephritis and vascular morbidity are prominent determinants of outcome in systemic lupus erythematosus (SLE), we studied the distribution and prognostic effect the ACE genotype might have on the outcome of SLE. METHODS: Fifty-six consecutive Israeli SLE patients and 48 (sex and ethnic origin matched) healthy individuals were evaluated for the ACE genotype by a polymerase chain reaction-based assay. The clinical and laboratory parameters of the patients as well as the SLE disease activity index (SLEDAI) and the presence of hypertension, diabetes mellitus, ischemic heart disease, congestive heart failure, and stroke were correlated with the ACE genotype. RESULTS: The distribution of the ACE genotype D/D, D/I, and I/I in the lupus group was 59%, 36%, and 5%, respectively, similar to the distribution in the control group (54%, 31%, and 15%, respectively). We failed to find any significant association between the ACE genotype and disease manifestations, SLEDAI, renal function, or cardiovascular and cerebrovascular morbidity. The clinical and laboratory parameters associated with renal outcome and vascular morbidity in our cohort are described. CONCLUSIONS: No difference was found between the distribution of the ACE genotype in lupus patients and the general population in Israel. Renal function as well as cardiovascular and cerebrovascular morbidity among Israeli patients with SLE are disease-related and independent of the ACE gene polymorphism.

Adolescent↗
PubMed1999

Childhood Behçet's disease: clinical features and comparison with adult-onset disease.

OBJECTIVE: To study the clinical spectrum of Behçet's disease (BD) in childhood, in comparison to adult-onset disease. METHODS: Nineteen children, who fulfilled disease criteria up to the age of 16 yr, were studied. The results were compared to those of 34 adult patients with BD. An activity index and severity score were calculated for both study groups. RESULTS: The mean age of disease onset was 6.9+/-3.9 yr, similar ages of onset were found in males and females. The clinical spectrum of childhood BD resembled that of adult disease; however, the prevalence of certain manifestations was different between children and adults. Children with BD had significantly less genital ulcers, less vascular thromboses and more non-specific gastrointestinal symptoms, as well as central nervous system involvement and arthralgia. A relatively high prevalence of uveitis was found in childhood BD. The activity index and severity score were significantly lower in children than in adults. CONCLUSION: Our results point to a similar systemic expression of BD in children and adults; however, the disease seems to run a less severe course in children.

Adolescent↗
PubMed1999

Recurrent aphthous stomatitis in Behçet's disease: clinical features and correlation with systemic disease expression and severity.

Behçet's disease (BD) is a multisystem disease, in which recurrent aphthous stomatitis (RAS) is a universal finding. We studied the expression of RAS in patients with BD, and the correlation between major or minor RAS and systemic expression and severity of the disease. Thirty-five patients with BD were studied, of whom 13 (37%) had major, 21 (60%) had minor and one (3%) had herpetiform RAS. The frequency of major RAS was significantly higher compared with a control group of patients with idiopathic RAS (37% vs 9%, P < 0.05). The BD patients with major RAS had significantly more relapses of oral ulceration in a year, higher numbers of oral ulcers per relapse, and longer duration of aphthous episodes, compared with patients with minor RAS. Oral ulcers also appeared at a significantly younger age in patients with major than with minor RAS. However, the systemic expression of the disease, as well as the disease severity score, were similar in patients with major and minor RAS. The results of this study indicate that major RAS is common in patients with BD, and is associated with a more severe, repeated and prolonged oral disease. Nevertheless, the presence of major RAS in BD does not predict a more severe systemic illness.

Adolescent↗
PubMed1999

Controlled ovarian hyperstimulation: a state of neutrophil activation.

PROBLEM: To investigate if controlled ovarian hyperstimulation (COH) affects the expression of neutrophil adhesion molecules and if a correlation exists between neutrophil activation and serum sex-steroid levels. METHOD OF STUDY: The pilot study was carried out in the in vitro fertilization (IVF) unit of our department, and required no modification of our routine IVF protocol. Four patients arriving for baseline hormonal profile on day 1 of the menstrual cycle before initiation of COH (control group) and 11 patients admitted for oocyte recovery (study group) were included. Venous blood was obtained from all patients and examined for hormonal profile and neutrophil activation. The latter was performed by staining for the surface adhesion molecules beta2 integrin and L-selectin. Positive cell count and mean fluorescence intensity were determined by flow cytometry. RESULTS: While neutrophil L-selectin was significantly lower in the study group than in the control group, neutrophil beta2 integrin was nonsignificantly higher. Though no significant correlations were found between neutrophil adhesion molecules and patient age, serum estradiol level, and human chorionic gonadotropin level; neutrophil L-selectin was negatively correlated with serum progesterone levels. CONCLUSIONS: COH leads to neutrophil activation, which correlates with the degree of luteinization. Further studies are required to elucidate the relationship between the immune system and COH. These may lead to new strategies for promoting fertility and preventing complications of COH.

Adult↗
PubMed1998

Mode of presentation and multisystem involvement in Behçet's disease: the influence of sex and age of disease onset.

OBJECTIVE: To evaluate the correlation between the age at onset of Behcet's disease (BD) and sex distribution, mode of disease appearance, and number of organs involved during the disease. METHODS: BD was defined according to the International Study Group criteria. Data from medical files and from patient interviews were collected. Results were analyzed for children and adults, according to age at disease onset. A systemic involvement index was calculated as the sum of visceral organ systems involved. RESULTS: Fifty-nine patients with BD were studied, 26 male and 33 female. The mean age at disease onset was 8.4 +/- 4.5 years in children and 29.8 +/- 7.9 years in adults. The age of onset was significantly lower in male versus female patients. BD presented in children almost entirely as recurrent aphthous stomatitis, while in adults, less than one-third of patients presented first with oral ulcers. The mean age at disease onset of patients who presented first with oral ulcers was significantly lower than the age of patients presenting first with non-oral aphthosis. The mean systemic involvement index was higher in adult onset than in juvenile onset disease. A significant linear correlation was found between age of disease onset and total number of visceral organ systems involved. CONCLUSION: BD was observed to occur earlier in males than in females. The first manifestation of BD in children is almost exclusively in the form of oral ulcers, while older patients have a large proportion of non-oral aphthosis as their first disease manifestation. Disease onset at an older age is positively correlated with increased disease spectrum.

Adult↗
PubMed1997

Seasonal variations in manifestations and activity of systemic lupus erythematosus.

The purpose of the present study was to investigate a possible seasonal pattern in various clinical and laboratory manifestations in a group of systemic lupus erythamatosus (SLE) patients. One hundred and five SLE patients were followed up during a 4 yr period. Data on each of the clinical and laboratory variables examined, as well as the results of the disease activity index (SLEDAI), were plotted against the month during which they were obtained. Photosensitivity was the only variable to show a seasonal pattern, having higher scores during the summer months (1.04 +/- 0.16 in July vs 0.58 +/- 0.12 in December). We were unable to show seasonal patterns in any of the other variables examined. As a group, SLE patients do not show any significant seasonal pattern in disease manifestations and activity, except for photosensitivity. However, such a pattern may exist for the individual patient.

Adolescent↗
PubMed1997

Seasons of the year and activity of SLE and Behcet's disease.

Patients with systemic lupus erythematosus (SLE) were evaluated using a telephone questionnaire on the activity of various disease manifestations during the seasons of the past year. The results were compared to those of patients with Behcet's disease (BD), using the same questionnaires, and analyzed in relation to the mean temperature, humidity, barometric pressure, and ultraviolet radiation (UVR) in the patient's location, obtained from the official Israeli Meteorological Service. It was found that SLE patients had a tendency towards winter worsening of clinical manifestations, shown as increased incidence of joint pains, weakness, fatigue, Raynaud's phenomenon, and rash, as well as increased number of hospital admissions, sick leaves, and need to raise the dose of medications. The symptoms of patients with BD were not correlated to seasons of the year, except for increased joint pains in autumn and spring. We suggest that UVR accumulation might cause exacerbations in SLE patients several months after prolonged exposure to sunlight in the summer.

Adult↗
PubMed1995

Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils.

Since colchicine-sensitive microtubules regulate the expression and topography of surface glycoproteins on a variety of cells, we sought evidence that colchicine interferes with neutrophil-endothelial interactions by altering the number and/or distribution of selectins on endothelial cells and neutrophils. Extremely low, prophylactic, concentrations of colchicine (IC50 = 3 nM) eliminated the E-selectin-mediated increment in endothelial adhesiveness for neutrophils in response to IL-1 (P < 0.001) or TNF alpha (P < 0.001) by changing the distribution, but not the number, of E-selectin molecules on the surface of the endothelial cells. Colchicine inhibited stimulated endothelial adhesiveness via its effects on microtubules since vinblastine, an agent which perturbs microtubule function by other mechanisms, diminished adhesiveness whereas the photoinactivated colchicine derivative gamma-lumicolchicine was inactive. Colchicine had no effect on cell viability. At higher, therapeutic, concentrations colchicine (IC50 = 300 nM, P < 0.001) also diminished the expression of L-selectin on the surface of neutrophils (but not lymphocytes) without affecting expression of the beta 2-integrin CD11b/CD18. In confirmation, L-selectin expression was strikingly reduced (relative to CD11b/CD18 expression) on neutrophils from two individuals who had ingested therapeutic doses of colchicine. These results suggest that colchicine may exert its prophylactic effects on cytokine-provoked inflammation by diminishing the qualitative expression of E-selectin on endothelium, and its therapeutic effects by diminishing the quantitative expression of L-selectin on neutrophils.

Animals↗
PubMed1994

Immunocomplexes stimulate different signalling events to chemoattractants in the neutrophil and regulate L-selectin and beta 2-integrin expression differently.

Neutrophils express receptors for numerous phlogistons which, when occupied, trigger distinct signal-transduction pathways. Previous studies have shown that stimulation of neutrophils with chemoattractants induces shedding of the adhesive molecule L-selectin and increased expression of the beta 2-integrin CD11b/CD18. We determined the effect of ligation of classic, G-protein-linked chemoattractant receptors [C5a, interleukin-8 (IL-8), formylmethionyl-leucylphenylalanine (FMLP) and substance P], receptors for the Fc portion of IgG (Fc gamma receptors) and receptors for transforming growth factor beta (TGF beta) on expression of adhesive molecules by neutrophils and the stimulus-transduction mechanisms thought to mediate these changes. We were surprised to observe that occupancy of Fc gamma receptors by immunocomplexes (BSA-anti-BSA) stimulated increased expression by neutrophils of CD11b/CD18 at concentrations which did not affect L-selectin expression (EC50 9 micrograms/ml versus 350 micrograms/ml respectively, P < 0.00001, n = 5). In contrast, similar to previous studies, recombinant C5a, recombinant IL-8 and FMLP all stimulated increased expression of CD11b/CD18 (170-260% of basal, P < 0.001, n = 5) and shedding of L-selectin (56-75% reduction from basal, P < 0.001, n = 5) at similar concentrations and with similar potencies (EC50 = 2, 5, and 3 nM respectively). In contrast, neither TGF beta 1 nor, surprisingly, substance P affected expression of CD11b/CD18 or L-selectin. The regulation of expression of CD11b/CD18 or L-selectin in response to FMLP or immunocomplexes was unaffected by cytochalasin B (5 micrograms/ml) or the tyrosine kinase inhibitor tyrphostin-25 (25 microM). Although occupancy of both chemoattractant (FMLP) and Fc gamma receptors stimulated increments in the second messenger diacylglycerol, disruption of actin microfilaments by cytochalasin B enhanced diacylglycerol generation in response to FMLP but not in response to ligation of Fc gamma receptors. Moreover, both FMLP and immune aggregates provoked fluxes of intracellular Ca2+ concentration which differed with respect to both magnitude and kinetics and did not correlate well with regulation of adhesive-molecule expression. As upregulation of CD11b/CD18 is tightly linked to exocytosis of specific granules, these results suggest that shedding of L-selectin by activated neutrophils is not linked to exocytosis. These studies provide further evidence that receptors for chemoattractants and immunocomplexes on the neutrophil are linked to multiple signalling pathways.

Actins↗
PubMed1994

Intravascular neutrophil activation in systemic lupus erythematosus (SLE): dissociation between increased expression of CD11b/CD18 and diminished expression of L-selectin on neutrophils from patients with active SLE.

Previous studies have shown that neutrophils in the circulation of patients with active systemic lupus erythematosus (SLE) are activated as judged by their increased surface expression of the beta 2-integrin CD11b/CD18. Since activation of neutrophils leads to altered expression of another adhesion molecule, L-selectin (LS), we examined neutrophils from patients with SLE for changes in the expression of CD11b/CD18 and LS by cytofluorographic analysis of immunofluorescent-labeled cells. Overall there was no difference between surface expression of CD11b/CD18 on neutrophils from SLE patients or controls [mean fluorescence 225 +/- 26 vs 225 +/- 13 relative fluorescence units (RFU), respectively]. However, as previously reported, neutrophils from patients with more active disease (activity score > or = 3, UCH Middlesex activity score) expressed greater CD11b/CD18 than neutrophils from controls (319 +/- 40 RFU, P < 0.03, n = 9) or from patients with less active disease (193 +/- 10 RFU, P < 0.006). Indeed, CD11b/CD18 expression correlated directly with disease activity (r = 0.54, P < 0.02). Stimulation of neutrophils ex vivo with the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (100 nM) induced up-regulation of CD11b/CD18 in cells from both SLE patients and controls (205 +/- 12% vs 239 +/- 15% of basal, respectively), but neutrophils from the most active patients (score > or = 3) increased CD11b/CD18 expression less than controls (175 +/- 12% of basal, P < 0.003, n = 9). The magnitude of the stimulated increment in expression of CD11b/CD18 on neutrophils correlated inversely with SLE activity (r = -0.64, P < 0.003, n = 20). Surprisingly, we observed no change in LS expression on neutrophils from SLE patients compared to controls (143 +/- 14 vs 141 +/- 16 RFU, respectively) even in patients with the highest activity indices (154 +/- 21 RFU). In contrast to CD11b/CD18, there was no correlation between LS expression and disease activity (r = 0.12, P = NS). Stimulation of neutrophils reduced the expression of LS similarly in both controls and SLE patients (67 +/- 3% vs 58 +/- 4% reduction, respectively) and did not correlate with disease activity (r = 0.07, P = NS, n = 20). These results show, for the first time, that changes in CD11b/CD18 expression do not correlate with LS expression on neutrophils from patients with active SLE.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, CD↗
PubMed1993

Correlation between serum levels of soluble tumor necrosis factor receptor and disease activity in systemic lupus erythematosus.

OBJECTIVE: To determine the value of measurement of serum soluble tumor necrosis factor receptor (sTNFR), compared with established parameters such as anti-double-stranded DNA, in monitoring systemic lupus erythematosus (SLE) disease activity, and to determine whether serum sTNFR are bioactive and can effectively inhibit TNF bioactivity. METHODS: Fifty-three consecutive ambulatory or hospitalized SLE patients and 140 consecutive healthy subjects were enrolled in a prospective cohort study. Serum levels of sTNFR were measured by a unique 2-sided capture enzyme-linked immunosorbent assay using mouse monoclonal antibodies and rabbit antisera against the sTNFR. RESULTS: The mean +/- SD concentrations of both the p55 (type I) and p75 (type II) soluble receptors were significantly higher in a group of 46 SLE patients than in controls: 1.89 +/- 0.89 ng/ml versus 0.77 +/- 0.19 ng/ml and 7.25 +/- 3.89 ng/ml versus 3.02 +/- 0.57 ng/ml, respectively (P < 0.0001 for both). The incidence and the extent of the increase among the healthy subjects and these patients (as well as in 7 additional patients on whom sequential studies were performed) correlated with disease activity more than did the occurrence of serum anti-DNA antibodies (correlation coefficients with disease activity 0.81 and 0.85 for p55 and p75 sTNFR, respectively, and 0.51 for anti-DNA antibodies). The increase in sTNFR levels seems to reflect, largely, enhanced formation, and only to a minor extent, reduced clearance due to impairment of renal function. Sera of the SLE patients had a marked inhibitory effect on the in vitro cytocidal activity of TNF, and this was shown to result entirely from their higher sTNFR receptor concentration. CONCLUSION: An increase in serum levels of sTNFR may become a useful marker for SLE activity since it shows a stronger correlation than do any other laboratory or clinical parameters employed presently in the daily clinical setting. At the concentrations attained in the serum of SLE patients, sTNFR effectively inhibit the bioactivity of TNF and may thus be a significant determinant of the intensity of the manifestations of SLE.

Adult↗
PubMed1993

Treatment of systemic lupus erythematosus by prolonged administration of high dose intravenous immunoglobulin: report of 2 cases.

Two patients with life threatening manifestations of systemic lupus erythematosus (SLE), unresponsive to corticosteroid and immunosuppressive therapy, were treated with high dose intravenous immunoglobulin (IVIG). Following IVIG therapy, lupus pneumonitis and encephalitis in the first patient, and lupus nephritis in the second patient, resolved. Continuous treatment with IVIG, every 4 weeks for up to 20 months induced a prolonged clinical and laboratory remission. Treatment with cytotoxic agents was stopped, and the dosage of corticosteroids lowered. Exacerbation of lupus nephritis occurred in the second patient after 10 months of IVIG therapy. We suggest that prolonged use of high dose IVIG may be a useful therapy for acute exacerbations of SLE and for inducing prolonged remissions.

Adult↗