LUCAS YUGO SHIGUEHARA YAMAKAMI
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- Ovarian reserve in adult patients with childhood-onset lupus: a possible deleterious effect of methotrexate?(2014) ARAUJO, D. B. de; YAMAKAMI, L. Y. S.; AIKAWA, N. E.; BONFA, E.; VIANA, V. S. T.; PASOTO, S. G.; PEREIRA, R. M. R.; SERAFIN, P. C.; BORBA, E. F.; SILVA, C. A.Objectives: To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c-SLE). Method: Fifty-seven adult c-SLE female patients and 21 healthy controls were evaluated for anti-CoL. Ovarian reserve was assessed by: follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, anti-Mullerian hormone (AMH), and antral follicle count (AFC). Demographic data, menstrual abnormalities, disease activity, damage, and treatment were also analysed. Results: The median current age was similar in adult c-SLE patients and controls (27.7 vs. 27.7 years, p = 0.414). The medians of AMH (1.1 vs. 1.5 ng/mL, p = 0.037) and AFC (6 vs. 16, p < 0.001) were significantly reduced in SLE patients compared to controls without significant menstrual abnormalities. Anti-CoL were solely observed in c-SLE patients (16% vs. 0%, p = 0.103) and were not associated with demographic data, ovarian reserve parameters, disease activity/damage, and treatment. Further evaluation of c-SLE patients treated with cyclophosphamide revealed a higher median of FSH levels compared to c-SLE patients not treated with cyclophosphamide and controls (8.8 vs. 5.7 vs. 5.6 IU/L, p = 0.032) and lower median AMH (0.4 vs. 1.5 vs. 1.5 ng/mL, p = 0.004) and AFC (4.0 vs. 6.5 vs. 16 IU/L, p = 0.001) levels. Nineteen patients treated exclusively with methotrexate demonstrated a negative correlation between the cumulative dose and AMH levels (p = 0.027, r = -0.507). Conclusions: The present study demonstrated for the first time that a high cumulative methotrexate dose is a possible cause of subclinical ovarian dysfunction in adult c-SLE patients. Further studies are required to confirm this deleterious effect in other rheumatic diseases, particularly juvenile idiopathic arthritis and idiopathic inflammatory myopathy.
article 17 Citação(ões) na Scopus Reduction of ovarian reserve in adult patients with dermatomyositis(2015) SOUZA, F. H. C. de; SHINJO, S. K.; YAMAKAMI, L. Y. S.; VIANA, V. S. T.; BARACAT, E. C.; BONFA, E.; SILVA, C. A.Objective To assess ovarian reserve markers and anti-corpus luteum (anti-CoL) antibodies in dermatomyositis (DM) patients. Methods Forty female DM patients were invited to participate. Exclusion criteria included hormonal contraceptive use within the last six months, neoplasia associations, overlapped systemic autoimmune diseases, current pregnancy, gynaecological surgery and individual choice not to participate. The final experimental group for this cross-sectional study included 16 DM patients and 23 healthy controls, each of whom was evaluated during the early follicular phase of the menstrual cycle. Values for IgG anti-CoL (via immunoblotting), follicle stimulating hormone (FSH), estradiol, inhibin B, anti-Mullerian hormone (AMH) serum levels (via ELISA) and sonographic antral follicle count (AFC) were determined. Results DM patients and controls were of comparable mean age (p>0.05). The mean age of DM onset was 29.1 +/- 4.7 years, with disease duration of 5.6 +/- 3.2 years. Menstrual cycle characteristics, comorbidity and lifestyle were similar amongst patients in both groups (p>0.05). AMH values of <= lng/mL (p=0.027) and AFC values (p=0.017) were significantly reduced in DM patients relative to the control group, whereas serum estradiol levels (p<0.001) were higher in DM patients compared to controls. In contrast, serum FSH and inhibin B levels, ovarian volumes, and anti-CoL antibody frequency were similar in both groups. Differences in AFC and estradiol were determined to be significant following Bonferroni correction for multiple testing. Conclusion We identified a diminished ovarian reserve in DM patients of reproductive age. Further studies are necessary to assess the idiopathic inflammatory myopathy-related factors involved in the ovarian impairment of this patient population.- Clark CA, Laskin CA. Ovarian reserve in antiphospholipid syndrome: the jury is still out. Lupus 2015; 24: 773(2015) YAMAKAMI, L. Y. S.; SERAFINI, P. C.; ARAUJO, D. B. de; BONFA, E.; LEON, E. P.; BARACAT, E. C.; SILVA, C. A.
conferenceObject DO WOMEN WITH PRIMARY ANTIPHOSPHOLIPID SYNDROME HAVE LOW OVARIAN RESERVE?(2013) YAMAKAMI, L. Y. S.; SERAFINI, P. C.; ARAUJO, D. B.; BONFA, E.; BARACAT, E. C.; SILVA, C. A.- Autoimmune primary ovarian insufficiency(2014) SILVA, C. A.; YAMAKAMI, L. Y. S.; AIKAWA, N. E.; ARAUJO, D. B.; CARVALHO, J. F.; BONFA, E.Primary ovarian insufficiency (POI) is defined as sustained amenorrhea, increased follicle-stimulating hormone and low estrogen levels, whereas diminished ovarian reserve (DOR) is characterized as regular menses and alterations of ovarian reserve tests. POI of autoimmune origin may be associated with adrenal autoimmunity, non-adrenal autoimmunity or isolated. This autoimmune disease is characterized by serum ovarian, adrenocortical or steroidogenic cell autoantibodies. POI of adrenal autoimmune origin is the most frequent type observed in 60-80% of patients. Clinically, amenorrhea is the hallmark of POI, however before menstruation stops completely, irregular cycles occur. Infertility, hot flushes, vaginal atrophy, and dyspareunia are also common. Autoimmune oophoritis is characterized by mononuclear inflammatory cell infiltrate in the theca cells of growing follicles, with early stage follicles without lymphocytic infiltration. This infiltrate includes plasma, B and T-cells. A novel classification criterion for autoimmune POI/DOR is proposed subdividing in three distinct categories (possible, probable and confirmed) according to autoantibodies, autoimmune disease and ovarian histology. Unfortunately, up to date guidelines for the treatment of autoimmune oophoritis are not available. Strategies to POI treatment include hormone replacement and infertility therapy. Assisted conception with donated oocytes has been proven to achieve pregnancy by intra cytoplasmic sperm injection in POI women.
- SUBCLINICAL OVARIAN DYSFUNCTION IN TAKAYASU ARTERITIS PATIENTS(2014) MONT'ALVERNE, A. R. S.; PEREIRA, R. M. R.; YAMAKAMI, L. Y. S.; VIANA, V. S. T.; BARACAT, E. C.; BONFA, E.; SILVA, C. A.
- Ovarian reserve in women with primary antiphospholipid syndrome(2014) YAMAKAMI, L. Y. S.; SERAFINI, P. C.; ARAUJO, D. B. de; BONFA, E.; LEON, E. P.; BARACAT, E. C.; SILVA, C. A.Objective: The objective of this paper is to evaluate ovarian reserve in primary antiphospholipid syndrome (PAPS) women and the association between ovarian reserve tests and clinical and laboratorial parameters, and anti-corpus luteum antibody (anti-CoL). Methods: We screened 85 female patients between 18 to 40 years old with APS. Of these, 67 patients were excluded because of association with other autoimmune diseases (n = 42), contraindication or unwillingness to stop hormonal contraceptive (n = 21), current pregnancy or breastfeeding (n = 3) and previous ovarian surgery (n = 1). Therefore, a cross-sectional study was conducted in 18 PAPS patients and 24 healthy women. They were evaluated at early follicular phase with measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Mullerian hormone (AMH) and sonographic antral follicle count (AFC). Serum measurement of anti-CoL was determined by immunoblot analysis. All analyses were performed after at least six months from the last intake of hormonal contraceptive and resumption of menstruation. Results: The mean age was comparable in PAPS and controls (33.0 +/- 5.0 vs. 30.4 +/- 7.0 years; p = 0.19). Regarding ovarian reserve tests, the frequencies of low AFC (<= 10) (56% vs. 22%, p = 0.04) and very low AFC (<= 5) (37% vs. 9%, p = 0.04) were significantly higher in PAPS patients than controls. Trends of higher frequencies of reduced (< 1.0 ng/ml), low (< 0.5 ng/ml) and negligible (< 0.2 ng/ml) AMH levels were found in PAPS patients (p = 0.08, p = 0.07 and p = 0.07, respectively). FSH, LH and estradiol were similar in patients and controls. There was no association between low ovarian reserve and specific types of antiphospholipid antibodies. Anti-CoL was solely observed in PAPS patients (11% vs. 0%; p = 0.177) and was not related to ovarian reserve tests. Conclusion: Women suffering from PAPS possessed reduced ovarian reserve, with prevalence greater than 50%.
- Severe hemorrhagic corpus luteum complicating anticoagulation in antiphospholipid syndrome(2011) YAMAKAMI, L. Y. S.; ARAUJO, D. B. de; SILVA, C. A.; BARACAT, E. C.; CARVALHO, J. F. deAntiphospholipid syndrome (APS) is a disorder of coagulation that causes thrombosis as well as pregnancy-related complications, occurring due to the autoimmune production of antibodies against phospholipid. Full anticoagulation is the cornerstone therapy in patients with thrombosis history, and this can lead to major bleeding. During a 3-year period, 300 primary and secondary APS patients were followed up at the Rheumatology Division of the authors' University Hospital. Of them, 255 (85%) were women and 180 (60%) were of reproductive age. Three of them (1%) had severe hemorrhagic corpus luteum while receiving long-term anticoagulation treatment and are described in this report. All of them were taking warfarin, had elevated international normalized ratio (> 4.0) and required prompt blood transfusion and emergency surgery. Therefore, we strongly recommend that all women with APS under anticoagulation should have ovulation suppressed with either intramuscular depot-medroxyprogesterone acetate or oral desogestrel. Lupus (2011) 20, 523-526.