Tibolone in postmenopausal women with systemic lupus erythematosus: A pilot study

Objective: To determine the influence of the use of tibolone on the frequency of flares of systemic lupus erythematosus (SLE) in postmenopausal patients. Methods: Thirty patients with inactive or controlled SLE were included in the study. Patients were randomized to receive a 12-month course of either tibolona (2.5 mg/day) or placebo. The following were investigated: hypoestrogenism symptoms by Kupperman index, weight; anti-dsDNA antibodies; SLE flares (frequency) assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and biochemical profile (total cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, complement components [C3/C4], alpha 1-acid glycoprotein, urea, creatinine, 24-h proteinuria, C-reactive protein and erythrocyte sedimentation rate). Results: The reduction in Kupperman index was greater in the patients using tibolone than in those using placebo. I-lie mean SLEDAI was not different between the groups during the study as well as SLE flare frequency (tibolone: 2/15 [13.3%] vs. placebo: 1/15 [6.7%]; p = 0.54). All cases of flares were considered mild to moderate. Although the groups were similar at the baseline evaluation, after 6 and 12 months of treatment lower values were found in the tibolone group for triglycerides (6 months: 161.6 +/- 30.9 mg/dl vs. 194.4 +/- 46.5: p = 0.04: 12 months 163.7 +/- 29.8 mg/dl vs. 204.1 +/- 49.9 mg/dl; p = 0.02: tibolone vs. placebo group, respectively) and for HDL-C (6 months: 40.7 +/- 10.7 mg/dl vs. 53.4 +/- 16.5; p = 0.02; 12 months: 47.2 +/- 7.9 mg/dl vs. 63.2 +/- 16.3 mg/dl; p < 0.01: tibolone vs. placebo group, respectively). There were no differences between the two groups in any of the remaining variables. Conclusion: In patients with inactive or stable SLE, the short-term use of tibolone did not significantly affect the frequency of flares. In addition, tibolone was well tolerated and effective to control hypoestrogenism related symptoms in SLE patients. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Relationship between first polar body morphology before intracytoplasmic sperm injection and fertilization rate, cleavage rate, and embryo quality

Objectives: To evaluate the influence of the morphology of the first polar body (PB) on intracytoplasmic sperm injection (ICSI) outcomes. Methods: The morphology of the first PB was assessed in 3177 metaphase 11 oocytes and classified as: intact and normal size, fragmented, or enlarged size. The rates of fertilization, cleavage, and embryo quality were evaluated on day 2. Results: The rates of fertilization, cleavage, and formation of good quality embryos resulting from the insemination of oocytes with an enlarged first PB (20.7%, 18.7%, and 5.0%, respectively) were significantly lower than those for oocytes with an intact first PB of normal size (70.8%, 62.5%, and 19%, respectively) or a fragmented first PB (69.7%, 60.5%, and 17.1%, respectively). Rates did not differ significantly between oocytes with an intact first PB of normal size and oocytes with a fragmented first PB (P>0.05). Conclusions: The presence of an enlarged PB is related to poorer rates of fertilization, cleavage, and top quality embryos. However, identification of first PB fragmentation does not seem to interfere with ICSI outcomes. (C) 2008 International Federation ofGynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Determination of Cyclophosphamide Enantiomers in Plasma by LC-MS/MS: Application to Pharmacokinetics in Breast Cancer and Lupus Nephritis Patients

This article describes the enantioseleclive analysis of cyclophosphamide (CPA) in human plasma using LC-MS/MS. CPA enantiomers were extracted from plasma using a mixture of ethyl acetate and chloroform (75:25, v/v). The enantiomers were separated on a Chiralcel(R) OD-R column, with the mobile phase consisting of a mixture of acetonitrile and water (75:25, v/v) plus 0.2% formic acid. The protonaled ions and their respective product ions were monitored using two functions, 261 > 141 for CPA enantiomers and 189 > 104 for the internal standard (antipyrine). Recovery rates were higher than 95% and the quantification limit was 2.5-ng/ml plasma for both enantiomers. The coefficients of variation and the relative errors obtained for the validation of intra- and interassay precision and accuracy were less than 10%. The method was applied for the investigation of the enantioselective pharmacokinetics of CPA in a lupus nephritis patient treated with 1 g CPA infused over 2 h and in a breast cancer patient treated with 0.9 g infused over 1 h. No stereoselectivity in the pharmacokinetic parameters was observed for either patient. Clearance values of 2.63 and 2.93 l/h and of 3.36 and 3.61 l/h for (-)-(S) and (+)-(R)-CPA were obtained for the breast cancer and lupus nephritis patient., respectively. Chirality 21:383-389, 2009. (C) 2008 Wiley-Liss, Inc.

Supplemented tissue culture medium 199 is a better medium for in vitro maturation of oocytes from women with polycystic ovary syndrome women than human tubal fluid

Objective: To compare oocyte maturation, fertilization and cleavage rates, and embryonic developmental quality after culture of human immature oocytes from polycystic ovary syndrome (PCOS) patients in human tubal fluid (HTF) or tissue culture medium (TCM) 199. Design: Prospective, randomized, controlled trial. Setting: University hospital. Patient(s): Thirteen women undergoing 23 in vitro maturation cycles, from whom 119 oocytes were retrieved. Intervention(s): Cumulus-enclosed germinal vesicle-stage oocytes matured in TCM-199-supplemented or HTF-supplemented media. Main Outcome Measure(s): Oocyte maturation and fertilization rates, embryonic developmental quality. Result(s): Significant differences were observed between TCM 199 and HTF regarding maturation rate (82% vs. 56.9%), fertilization rate (70% vs. 39.4%), and embryo quality (81.3% vs. 41.7%). Conclusion(S): Human tubal fluid medium, although widely used for embryo fertilization and maintenance in IVF techniques, is not,in appropriate medium for the maturation of oocytes obtained from PCOS patients in nonstimulated cycles. (Fertil Steril(R) 2009;91:509-13. (C)2009 by American Society for Reproductive Medicine.)

Both a combined oral contraceptive and depot medroxyprogesterone acetate impair endothelial function in young women

Background: The study was conducted to determine whether the use of a combined oral contraceptive (COC) or depot medroxyprogesterone acetate (DMPA) interferes with endothelial function. Study Design: The study was conducted on 100 women between the ages of 18 and 30 years. Fifty women had not used hormonal contraception (control group) for at least 12 months, 25 were current users of a COC (ethinylestradiol 30 mcg+levonorgestrel 150 mcg) and 25 were current users of DMPA (150 mg) for at least a 6-month period. All women were evaluated for brachial flow-mediated dilation (FMD), intima-media thickness, carotid distensibility and stiffness index, arterial pressure, body mass index, waist circumference, heart rate and lipid profile. Results: A significant difference in FMD was observed between the COC and control groups (6.4 +/- 2.2% vs. 8,7 +/- 3.4%, p<.01) and between the DMPA and control groups (6.2 +/- 2.1% vs. 8.7 +/- 3.4%, p<.01). The DMPA group had lower values of total cholesterol (TC) and low-density lipoprotein (LDL-C) than COC users and the control group (TC: DMPA=139.9 +/- 21.5 mg/dL vs. controls=167.1 +/- 29.2 mg/dL vs. COC=168.2 +/- 37.5. p=.001; LDL-C: DMPA-85.3 +/- 20.1 mg/dL vs. controls=102 +/- 24.5 mg/dL vs. COC=106.7 +/- 33.3 mg/dL, p=.01). The control group had higher levels of high-density lipoprotein (HDL-C) than the DMPA and COC groups (controls=52.4 +/- 14.1 mg/dL vs. DMPA=42.2 +/- 7.2 mg/dL vs. COC=45.4 +/- 9.1 mg/dL, p=.001). No significant differences were observed regarding the other variables. Conclusions: FMD was lower among COC and DMPA users, Suggesting that these hormonal contraceptives may promote endothelial dysfunction. (C) 2009 Elsevier Inc. All rights reserved.

Primary adenocarcinoma of the fallopian tube as an incidental finding during surgery in a postmenopausal patient with unspecific pelvic pain

Primary fallopian tube carcinoma (PFTC) is a rare gynecologic neoplasm and is usually diagnosed late and presents classically with a,characteristic group of symptoms. We describe a case of a 76-year-old woman who underwent TVS requested by the family physician due to unspecific pelvic pain. An adnexal mass was found with morphology associated with high levels of CA125 suggestive of a malignant tumor. During laparotomy, a mass located in the left tube was found. Histopathology confirmed PFTC. Total hysterectomy, salpingo-oophorectomy and adjuvant chemotherapy with carboplatin/paclitaxel were performed. The patient has not yet presented any signs of recurrence.

Sonographic evaluation of endothelial function in letrozole and tamoxifen users

Objectives: Studies have shown that women previously treated for breast cancer present fewer cardiovascular events, indicating a possible protective effect of tamoxifen treatment. The effects of these aromatase inhibitors on cardiovascular protection remain controversial. The aim of this study was to compare some cardiovascular risk markers among breast cancer survivors following treatment with tamoxifen group (TMXg), letrozole group (LTZg) or no endocrine treatment group (NETg). Methods: A total of 103 breast cancer survivors: 35 using TMXg, 34 using letrozole group (LTZg) and 34 using no endocrine treatment group (NETg) were evaluated. Ultrasonographic evaluation of brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (IMT) and stiffness index (beta); blood total cholesterol, HDL and triglycerides were assessed. Results: All three groups presented similar values of HDL and IMT. TMXg showed the lowest total cholesterol (219.29 +/- 36.31 mg/dL vs. 250.59 +/- 38.37 mg/dL vs. 245.09 +/- 35.35 mg/dL; TMXg vs. LTZg vs. NETg, respectively; p < 0.01-ANOVA), the highest triglycerides (139.34 +/- 41.82 mg/dL vs. 111.35 +/- 28.22 mg/dL vs.122.09 +/- 33.42 mg/dL; p < 0.01), the highest FMD (6.32 +/- 2.33% vs. 4.10 +/- 2.06% vs. 4.66 +/- 2.52%; p < 0.01) and the lowest stiffness index (beta) (5.08 +/- 1.68 vs. 6.28 +/- 1.75 vs. 5.99 +/- 1.86; p=0.01). LTZg did not differ significantly from NETg on any evaluated parameter. Conclusions: We did not observe any effect of LTZg on the evaluated cardiovascular risk parameters compared to NETg. As such, the observed difference on lipid values, stiffness index (beta) and FMD between women receiving tamoxifen anti letrozole might be best attributed to the beneficial effect of tamoxifen than to a detrimental effect of letrozole. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Lipid peroxidation and vitamin E in serum and follicular fluid of infertile women with peritoneal endometriosis submitted to controlled ovarian hyperstimulation: a pilot study

Objective: To assess the level of lipid peroxidation (LP) and vitamin E in the follicular fluid and serum of infertile patients, with or without endometriosis. who were submitted to ovulation induction for assisted reproduction procedures. Design: Prospective study. Setting: Assisted conception unit, university hospital. Patient(s): Infertile patients 20 to 38 years of age were selected prospectively and consecutively and were divided into the endometriosis group (17 patients with pelvic endometriosis) and the control group (19 patients with previous tubal ligation or male factor and without endometriosis). Intervention(s): Peripheral blood samples were collected on D1 (before the beginning of the use of gonadotropins), D2 (day of hCG administration), and D3 (day of oocyte retrieval). On D3, follicular-fluid samples free from blood contamination also were collected and stored. Main Outcome Measure(S): Lipid peroxidation was assessed by malondialdehyde quantification by spectrophotometry, and measurement of vitamin E was performed by HLPC. Result(s): On D1, no significant difference in LP was observed between groups. However, vitamin E levels were significantly higher in the control group. On D2, LP levels were significantly higher in the endometriosis group compared with in the control group, and vitamin E levels continued to be significantly higher in the control group. On D3, there was no significant difference in serum and follicular-fluid levels of LP and vitamin E between groups. However, on D3, vitamin E levels were found to be significantly higher in serum than in follicular fluid in both groups, whereas malondialdchyde levels were significantly lower in follicular fluid than in serum only in the control group. Conclusion(s): Before the beginning of ovulation induction, a significant decrease in vitamin E was observed in patients with endometriosis, perhaps because antioxidants are consumed during oxidation reactions. After ovulation induction with exogenous gonadotropins, the group of patients with endometriosis not only presented increased lipid peroxidation but also maintained lower vitamin E levels than the control group, a fact that hypothetically could compromise oocyte quality in endometriotic patients. However, on the day of oocyte retrieval, both serum LP potential and vitamin E levels were found to be similar in the two groups. (Fertil Steril(R) 2008; 90:2080-5. (C) 2008 by American Society for Reproductive Medicine.)

Pharmacokinetics of lidocaine and its metabolite in peridural anesthesia administered to pregnant women with gestational diabetes mellitus

Background Peridural blockade with lidocaine, bupivacaine, and fentanyl is an anesthetic procedure extensively used in obstetrics, justifying the pharmacokinetic study of these drugs during labor. Objective To investigate the influence of the physiopathological changes of gestational diabetes mellitus (GDM) on the pharmacokinetics of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in pregnant women subjected to peridural anesthesia. Patients and methods Ten normal pregnant women (group 1) and six pregnant women with GDM (group 2) were studied, all of them at term. The patients received 200 mg 2% lidocaine hydrochloride without a vasoconstrictor by the peridural locoregional route. Maternal blood samples were collected at predetermined times for the analysis of lidocaine and MEGX by chromatography and pharmacokinetic analysis. Results The median pharmacokinetic parameters of lidocaine for groups 1 and 2 (P <= 0.05), respectively, were as follows: for Cmax 879.11 and 1,145.58 ng/ml, AUC(0-infinity) 256.01 and 455.95 wg min(-1) ml(-1), Cl/f/kg 10.61 and 5.64 ml min(-1) kg(-1), and Vd/f/kg 3.26 and 2.19 L/kg. The median pharmacokinetic parameters of MEGX for groups 1 and 2 (P <= 0.05), respectively, were as follows: for Cmax 82.71 and 141.38 ng/ml, Tmax 44.71 and 193.14 min, t(1/2)alpha 7.64 and 59.77 min, alpha 0.097 and 0.012/min, and AUC(0-infinity) 29.91 and 108.23 mu g min(-1) ml(-1). Conclusion The present data permit us to conclude that the apparent clearance of lidocaine and MEGX was reduced in diabetic patients compared to normal women, suggesting that GDM inhibits the CYP1A2/CYP3A4 isoforms responsible for the metabolism of this drug and its metabolite.

UTERINE ULTRASONOGRAPHIC CHANGES DURING ENDOMETRIOSIS TREATMENT: A COMPARISON BETWEEN LEVONORGESTREL-RELEASING INTRAUTERINE DEVICES AND A GONADOTROPIN-RELEASING HORMONE AGONIST

We compared the effects of levonorgestrel-releasing intrauterine devices (LNG-IUD) and a gonadotropin-releasing hormone agonist (GnRHa) on uterine volume, uterine arteries pulsatility index (PI) and endometrial thickness before and after six months of endometriosis treatment. Sixty women aged 18-40 y were allocated randomly to one of two groups: LNG-IUDs were inserted in 30 women, and GnRHa monthly injections were performed on the other 30. All 60 women were submitted to transvaginal 2-D ultrasound scans on the day that the treatment started and then six months later. Measurements of uterine arteries PI, uterine volume and endometrial thickness were performed at both evaluations. The use of LNG-IUDs significantly decreased endometrial thickness (pre = 6.08 +/- 3.00 mm, post = 2.7 +/- 0.98 mm; mean +/- SD), as did the use of GnRHa (pre = 6.96 +/- 3.82 mm, post = 3.23 +/- 2.32 mm). The uterine volume decreased in the GnRHa group (pre = 86.67 +/- 28.38 cm(3), Post = 55.27 +/- 25.52 cm(3)), but not in the LNG-IUD group (pre = 75.77 +/- 20.88 cm(3), post = 75.97 +/- 26.62 cm(3)). Uterine arteries PI increased for both groups; however, the increase was higher in the GnRHa group (0.99 +/- 0.84 vs. 0.38 +/- 0.84, p = 0.007; PI increase in GnRHa and in LNG-IUD groups, respectively). In conclusion, levonorgestrel released directly onto the endometrium by the LNG-IUD induced smaller uterine changes than did the hypoestrogenism induced by GnRHa. Nevertheless, both promoted similar effects on endometrial thickness. (E-mail: wpmartins@gmail.com) (C) 2008 World Federation for Ultrasound in Medicine & Biology.

HLA-DRB association in neuromyelitis optica is different from that observed in multiple sclerosis

Until recently, neuromyelitis optica (NMO) was considered to be a sub-type of multiple sclerosis (MS), which has a strong predilection for Caucasian populations, whereas NMO is more frequent in non-Caucasian individuals. The objective of this study was to compare the HLA-DRB profile in Brazilian Mulatto patients with NMO spectrum disorders (NMOSDs) with that observed for Mulatto MS patients and healthy Mulatto controls. Twenty seven NMOSD patients (20 women), all seropositive for NMO-IgG, 29 MS patients and 28 Mulatto healthy blood donors were evaluated for HLA-DRB allele groups. HLA-DRB1*03 allele group was overrepresented in NMO patients compared with healthy controls (p = 0.0401; OR = 3.23, 95% CI: 1.07-9.82). In contrast, the HLA-DRB1*15 allele group was overrepresented in Brazilian MS patients (OR = 15.89, 95% CI: 3.51-71.85; p<0.0001). DRB3 was overrepresented in NMO (p = 0.0064), and DRB5 overrepresented in MS patients (p = 0.0001). The low frequency of HLA-DRB1*15 alleles was associated with the presence of long and central cord lesions at magnetic resonance. In addition, DRB1*15 alleles were associated with the fulfillment of the Barkhof criteria. In conclusion, these results indicate that the DRB profile of NMO patients is different from that observed for MS patients, further corroborating the distinction between NMO and MS.

Involvement of the central nervous system in the chronic form of Chagas` disease

Background and purpose: Apart from the central nervous system parasitic invasion in chagasic immunodeficient patients and strokes due to heart lesions provoked by the disease, the typical neurological syndromes of the chronic phase of Chagas` disease (CD) have not yet been characterized, although involvement of the peripheral nervous system has been well documented. This study aims at investigating whether specific signs of central nervous system impairment might be associated with the disease. Methods: Twenty-seven patients suffering from the chronic form of Chagas` disease (CCD) and an equal number of controls matched for sex, age, educational and socio-cultural background, and coming from the same geographical regions, were studied using neurological examinations, magnetic resonance images, and electroencephalographic frequency analysis. Results: Nineteen patients were at the stage A of the cardiac form of the disease (without documented structural lesions or heart failure). Dizziness, brisk reflexes, and ankle and knee areflexia were significantly more prevalent in the patients than in the controls. The significant findings in quantitative electroencephalogram were an increase in the theta relative power and a decrease in the theta dominant frequency at temporal-occipital derivations. Subcortical, white matter demyelination was associated with diffuse theta bursts and theta-delta slowing in two patients. Conclusions: Our findings suggest a discrete and unspecific functional cortical disorder and possible white matter lesions in CD. The focal nervous system abnormalities in CD documented here did not seem to cause significant functional damage or severely alter the patient`s quality of life. (C) 2008 Elsevier B.V. All rights reserved.

Characterizing the phenotypic manifestations of MFN2 R104W mutation in Charcot-Marie-Tooth type 2

Mutations of the mitofusin 2 (MFN2) gene have been reported to be the most common cause of the axonal form of Charcot Marie Tooth disease (CMT). The aim of this study was to describe a de novo MFN2 p.R104W mutation and characterize the associated phenotype. We screened the entire coding region of MFN2 gene and characterized its clinical phenotype, nerve conduction studies and sural nerve biopsy. Neuropsychological tests and brain MRI were also performed. A de nova mutation was found in exon 4 (c.310C > T; p.R104W). In addition to a severe and early onset axonal neuropathy, the patient presented learning problems, obesity, glucose intolerance, leukoencephalopathy, brain atrophy and evidence of myelin involvement and mitochondrial structural changes on sural nerve biopsy. These results suggest that MFN2 p.R104W mutation is as a hot-spot for MFN2 gene associated to a large and complex range of phenotypes. (C) 2011 Elsevier B.V. All rights reserved.

Expanded protocol of orofacial myofunctional evaluation with scores: Validity and reliability

Objective: Clinical evaluation of the stomatognathic system is indispensable for the diagnosis of orofacial myofunctional disorders. In order to obtain a more precise diagnosis, the protocol of orofacial myofunctional evaluation with scores (OMES protocol) (Int. J. Pediatr. Otorhinolaryngol. 72 (2008) 367-375) was expanded in terms of number of items and scale amplitude. The proposal of this study is to describe the expanded OMES protocol (OMES-E) for the evaluation of children. Validity of the protocol, reliability of the examiners and agreement between them were analyzed, as also were the sensitivity, specificity and predictive values of the instrument. Methods: The sample consisted of videorecorded images of 50 children, 25 boys (mean age = 8.4 years, SD = 1.8) and 25 girls (mean age = 8.2 years, SD = 1.7) selected at random from 200 samples. Three speech therapists prepared for orofacial myofunctional evaluation participated as examiners (E). The OMES and OMES-E protocols were used for evaluation on different days. E1 evaluated all images, E2 analyzed children with recordings from 1 to 25 and E3 analyzed children with recordings from 26 to 50. The validity of OMES-E was analyzed by comparing the instrument to the OMES protocol using the Pearson correlation test complemented with the split-half reliability test (p < 0.05). The linear weighted Kappa coefficient of agreement (Kw`), the sensitivity, specificity and predictive values and the prevalence of OMD were calculated. Results: There was a statistically significant correlation between the OMES and OMES-E protocols (0.79 > r < 0.94, p < 0.01) and a significant test-retest correlation with the OMES-E (0.75 > r < 0.86, p < 0.01), with a reliability range of 0.86-0.93. The correlation and reliability coefficients between examiners were: E1 x E2 (r = 0.74, 0.84), E1 x E3 (r = 0.70, 0.83) (p < 0.01). Kw` coefficients with moderate and good strength predominated. The OMES-E protocol presented mean sensitivity = 0.91, specificity = 0.77, positive predictive value = 0.87 and negative predictive value = 0.85. The mean prevalence of OMD was 0.58. Conclusion: The OMES-E protocol is valid and reliable for orofacial myofunctional evaluation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Modeling upper eyelid kinematics during spontaneous and reflex blinks

To test a mathematical model for measuring blinking kinematics. Spontaneous and reflex blinks of 23 healthy subjects were recorded with two different temporal resolutions. A magnetic search coil was used to record 77 blinks sampled at 200 Hz and 2 kHz in 13 subjects. A video system with low temporal resolution (30 Hz) was employed to register 60 blinks of 10 other subjects. The experimental data points were fitted with a model that assumes that the upper eyelid movement can be divided into two parts: an impulsive accelerated motion followed by a damped harmonic oscillation. All spontaneous and reflex blinks, including those recorded with low resolution, were well fitted by the model with a median coefficient of determination of 0.990. No significant difference was observed when the parameters of the blinks were estimated with the under-damped or critically damped solutions of the harmonic oscillator. On the other hand, the over-damped solution was not applicable to fit any movement. There was good agreement between the model and numerical estimation of the amplitude but not of maximum velocity. Spontaneous and reflex blinks can be mathematically described as consisting of two different phases. The down-phase is mainly an accelerated movement followed by a short time that represents the initial part of the damped harmonic oscillation. The latter is entirely responsible for the up-phase of the movement. Depending on the instantaneous characteristics of each movement, the under-damped or critically damped oscillation is better suited to describe the second phase of the blink. (C) 2010 Elsevier B.V. All rights reserved.