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.)

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.

TRPV1 Expression on Peritoneal Endometriosis Foci is Associated With Chronic Pelvic Pain

Objective: To investigate the expression of capsaicin receptor (transient receptor potential vanilloid type 1 [TRPV1]) in the peritoneal endometriosis foci of women with and without chronic pelvic pain (CPP). Methods: A case-control study was conducted on 49 women with endometriosis who underwent laparoscopy, 28 of whom had CPP and 21 without CPP. Samples from peritoneum of the rectouterine excavation (2 cm(2)) were obtained by laparoscopy, fixed in 4% formaldehyde, and underwent immunohistochemistry analysis using rabbit anti-TRPV1 (1:400) polyclonal antibody. Results: Image analysis revealed that the immunoreactivity for TRPV1 was more frequent in specimens (endometriosis foci) from women with CPP (n = 15 of 28, 53.6%), compared to samples from the endometriosis foci of women without CPP (n = 6 of 21, 28.6%; P = .04). There was no correlation with duration, intensity of pain, or stage of the disease (endometriosis). Discussion: The present study shows that TRPV1 expression in peritoneal endometriosis foci is related to CPP in women. However, this association is not related to the endometriosis stage. In view of the immunoreactivity for TRPV1 observed here, we believe that some endometriotic lesions may provide a scenario for TRPV1 to be tonically active and this activity may contribute to the underlying pathology of CPP.

Ovarian reserve evaluation: state of the art

Purpose Revise role of hormonal basal and dynamic tests, as well as ultrasonographic measures as ovarian reserve markers, in order to provide better counseling to subfertile couples. Methods Review of publications on the topic, with an emphasis on recent well designed articles. Results Currently available ovarian reserve tests do not provide sufficient evidence to be solely considered ideal, even for premature ovarian senescence patients who do not present subfertility complaints. However, these markers occupy important place in initial approach to treatment of subfertile couples, predicting unsatisfactory results that could be improved by differentiated induction schemes and reducing excessive psychological and financial burdens, and adverse effects. Conclusions In order to remedy the limitations due to the scarcity of strong evidence about this topic, future studies should try to clarify predictive value of markers in groups of specific diseases-related subfertility and pay special attention to propaedeutic multivariate models including anti-Mullerian hormone and antral follicle count.

Social anxiety disorder women easily recognize fearfull, sad and happy faces: The influence of gender

Background: It has been suggested that individuals with social anxiety disorder (SAD) are exaggeratedly concerned about approval and disapproval by others. Therefore, we assessed the recognition of facial expressions by individuals with SAD, in an attempt to overcome the limitations of previous studies. Methods: The sample was formed by 231 individuals (78 SAD patients and 153 healthy controls). All individuals were treatment naive, aged 18-30 years and with similar socioeconomic level. Participants judged which emotion (happiness, sadness, disgust, anger, fear, and surprise) was presented in the facial expression of stimuli displayed on a computer screen. The stimuli were manipulated in order to depict different emotional intensities, with the initial image being a neutral face (0%) and, as the individual moved on across images, the expressions increased their emotional intensity until reaching the total emotion (100%). The time, accuracy, and intensity necessary to perform judgments were evaluated. Results: The groups did not show statistically significant differences in respect to the number of correct judgments or to the time necessary to respond. However, women with SAD required less emotional intensity to recognize faces displaying fear (p = 0.002), sadness (p = 0.033) and happiness (p = 0.002), with no significant differences for the other emotions or men with SAD. Conclusions: The findings suggest that women with SAD are hypersensitive to threat-related and approval-related social cues. Future studies investigating the neural basis of the impaired processing of facial emotion in SAD using functional neuroimaging would be desirable and opportune. (C) 2009 Elsevier Ltd. All rights reserved.

Dorsal root ganglionectomy for the diagnosis of sensory neuropathies. Surgical technique and results

Background: Inflammatory diseases stand out among sensory neuronopathies because, in their active phase, they can be treated with immunosuppressive agents. Immunosuppressive therapy may present severe adverse effects and requires previous inflammatory activity confirmation. Sensory neuronopathies are diagnosed based on clinical and EMG findings. Diagnostic confirmation and identification of inflammatory activity are based on sensory ganglion histopathological examination. We describe the surgical technique used for dorsal root ganglionectomy in patients with clinical/EMG diagnosis of sensory neuronopathies. Methods: The sensory ganglion was obtained from 15 patients through a small T7-T8 hemilaminectomy and foraminotomy to expose the C7 root from its origin to the spinal nerve bifurcation. In 6 patients, the dural cuff supposed to contain the ganglion was resected en bloc; and in 9 patients, the ganglion was obtained through a longitudinal incision of the dural cuff and microsurgical dissection from the ventral and dorsal roots and radicular arteries. All ganglia were histopathologically examined. Results: No ganglion was found in the dural cuff in 2 patients submitted to en bloc removal, and the ganglion was removed in all patients who underwent microsurgical dissection. All but 2 patients that had ganglion examination presented a neuronopathy of nerve cell loss, 3 with mononuclear inflammatory infiltrate. These patients underwent immunosuppressive therapy, and 2 of them presented clinical improvement. No surgical complications were observed. Conclusions: Microsurgical dorsal root ganglionectomy for diagnosing inflammatory sensory ganglionopathies was effective and safe. Although safe, en bloc resection of the proximal dural cuff was not effective for this purpose. (c) 2008 Published by Elsevier Inc.

Evaluation of molar and incisor bite force in indigenous compared with white population in Brazil

The purpose of this study was to deter-mine maximum bite force in molar and incisor regions in young Brazilian indigenous individuals, who have had a natural diet since birth, and compare the sample with white Brazilian individuals. To do this, individuals were paired one-to-one (same weight, height, and Class I facial pattern). A secondary purpose was to elucidate the relation between bite force and gender in both populations. Eighty-two Brazilians took part in this study. Participants were aged between 18 and 28 years and were divided into two groups: 41 Xingu indigenous individuals and 41 white Brazilian individuals, with 28 men and 13 women in each group. The inclusion criteria were: having complete dentition; normal occlusion; no neurological, psychiatric or movement disorders.; no reports of toothaches; having satisfactory periodontal health; absence of large facial skeletal alterations (typical Class II and Class III individuals); and no previous treatments using occlusal splints. To measure maximum bite force, a digital dynamometer model IDDK (Kratos-Equipamentos Industriais Ltda, Cotia, Sao Paulo, Brazil) was used, with a capacity of 1000 N, adapted for oral conditions. Assessments were made in the first molar (right and left) and central incisive regions. Results reveal that mean maximum bite forces in indigenous individuals of the right molar is 421 N, left molar 429 N and incisor region is 194 14 and for white individuals of the right molar is 410 N, left molar 422 N and incisor region is 117 N. Comparing indigenous with white individuals, maximal bite force showed a tendency of being greater in the indigenous group. It was observed that the incisor region showed statistical significance (p < 0.0005) but no significance was observed in the molar region. Moreover, indigenous men showed the highest bite force values. (C) 2007 Elsevier Ltd. All rights reserved.

Secondary PSF/TFE3-associated renal cell carcinoma in a child treated for genitourinary rhabdomyosarcoma

Xp11.2 translocation-associated renal cell carcinoma (RCC) is a rare tumor that accounts for at least one-third of childhood RCC. Different reports have emphasized that previous radio/chemotherapy might be involved in its pathogenesis. We describe a child who developed a t(X;1) (p11.2;p34) associated RCC after previous treatment for genitourinary rhabdomyosarcoma in infancy. The presence of the PSF-TFE3 fusion has only been described in a very limited number of cases. Our report expands the spectrum of tumors in which RCC can arise in the pediatric age group after chemotherapy.

Accurate Determination of Energy Needs in Children and Adolescents With Cancer

Studies on children with cancer have suggested that energy expenditure may indeed be greater than predicted for healthy children. Nutritional assessment is important for intervention and for the prevention of complications associated with malnutrition. The present study aimed to describe the nutritional status, energy expenditure, and substrate utilization of children and adolescents with cancer compared to healthy children matched for age, sex, and body mass index. Subjects were evaluated by anthropometry, food intake pattern, and body composition analysis. Energy expenditure and substrate oxidation were measured by indirect calorimetry. Indirect calorimetry data, energy, and macronutrient intake, anthropometry, and body composition parameters showed no significant differences between groups. There was no evidence of increased energy expenditure or of a change in substrate utilization in children with cancer compared to the healthy group. The data regarding usual food consumption showed no significant differences between groups.

Detection of Clonal Immunoglobulin and T-Cell Receptor Gene Rearrangements in Childhood Acute Lymphoblastic Leukemia Using a Low-Cost PCR Strategy

Background Imunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements function as specific markers for minimal residual disease (MRD) which is one of the best predictors of outcome in childhood acute lymphoblastic leukemia (ALL) We recently reported on the prognostic value of MRD during the induction of remission through a simplified PCR method Here we report on gene rearrangement frequencies and offer guidelines for the application of the technique Procedure Two hundred thirty three children had DNA extracted from bone marrow Ig and TCR gene rearrangements were amplified using consensus primers and conventional PCR PCR products were submitted to homo/heteroduplex analysis A computer program was designed to define combinations of targets for clonal detection using a minimum set of primers and reactions Results At least one clonal marker could be detected in 98% of the patients and two markers in approximately 80% The most commonly rear ringed genes in precursor B cell ALL were IgH (75%) TCRD (59%) IgK (55%), and TCRG (54%) The most commonly rearranged genes for TALL were TCRG (100%) and TCRD (24%) The sensitivity of primers was limited to the detection of 1 leukemic cell among 100 normal cells Conclusions We propose that eight PCR reactions per ALL subtype would allow for the detection of two markers in most cases In addition these reactions ire suitable for MRD monitoring especially when aiming the selection of patients with high MRD levels (>= 10(-2)) at the end of induction therapy Such an approach would be very useful in centers with limited financial resources Pediatr Blood Cancer 2010 55 1278-1286 (C) 2010 Wiley Liss Inc

Methotrexate Withdrawal at 6 vs 12 Months in Juvenile Idiopathic Arthritis in Remission A Randomized Clinical Trial

Context Novel therapies have improved the remission rate in chronic inflammatory disorders including juvenile idiopathic arthritis (JIA). Therefore, strategies of tapering therapy and reliable parameters for detecting subclinical inflammation have now become challenging questions. Objectives To analyze whether longer methotrexate treatment during remission of JIA prevents flares after withdrawal of medication and whether specific biomarkers identify patients at risk for flares. Design, Setting, and Patients Prospective, open, multicenter, medication-withdrawal randomized clinical trial including 364 patients (median age, 11.0 years) with JIA recruited in 61 centers from 29 countries between February 2005 and June 2006. Patients were included at first confirmation of clinical remission while continuing medication. At the time of therapy withdrawal, levels of the phagocyte activation marker myeloid-related proteins 8 and 14 heterocomplex (MRP8/14) were determined. Intervention Patients were randomly assigned to continue with methotrexate therapy for either 6 months (group 1 [n = 183]) or 12 months (group 2 [n = 181]) after induction of disease remission. Main Outcome Measures Primary outcome was relapse rate in the 2 treatment groups; secondary outcome was time to relapse. In a prespecified cohort analysis, the prognostic accuracy of MRP8/14 concentrations for the risk of flares was assessed. Results Intention-to-treat analysis of the primary outcome revealed relapse within 24 months after the inclusion into the study in 98 of 183 patients (relapse rate, 56.7%) in group 1 and 94 of 181 (55.6%) in group 2. The odds ratio for group 1 vs group 2 was 1.02 (95% CI, 0.82-1.27; P=.86). The median relapse-free interval after inclusion was 21.0 months in group 1 and 23.0 months in group 2. The hazard ratio for group 1 vs group 2 was 1.07 (95% CI, 0.82-1.41; P=.61). Median follow-up duration after inclusion was 34.2 and 34.3 months in groups 1 and 2, respectively. Levels of MRP8/14 during remission were significantly higher in patients who subsequently developed flares (median, 715 [IQR, 320-1110] ng/mL) compared with patients maintaining stable remission (400 [IQR, 220-800] ng/mL; P=.003). Low MRP8/14 levels indicated a low risk of flares within the next 3 months following the biomarker test (area under the receiver operating characteristic curve, 0.76; 95% CI, 0.62-0.90). Conclusions In patients with JIA in remission, a 12-month vs 6-month withdrawal of methotrexate did not reduce the relapse rate. Higher MRP8/14 concentrations were associated with risk of relapse after discontinuing methotrexate.

Long-Term Outcome and Prognostic Factors of Juvenile Dermatomyositis: A Multinational, Multicenter Study of 490 Patients

Objective. To investigate the long-term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study. Methods. Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health-related quality of life (HRQOL). Results. A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross-sectional visit, 41.2-52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2-60.5% of the patients, depending on the activity measure used. Sixty-nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%. Conclusion. This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage.

Role of the CYP2D6, EPHX1, MPO, and NQO1 Genes in the Susceptibility to Acute Lymphoblastic Leukemia in Brazilian Children

Polymorphic variations of several genes associated with dietary effects and exposure to environmental carcinogens may influence susceptibility to leukemia development. The objective of the present study was to evaluate the effect of the polymorphisms of debrisoquine hydroxylase (CYP2D6), epoxide hydrolase (EPHX1), myeloperoxidase (MPO), and quinone-oxoreductase (NQO1), which have been implicated in xenobiotic metabolism, on the risk of childhood acute lymphoblastic leukemia (ALL). We evaluated the frequency of polymorphisms in the CYP2D6 (*3 and *4), EPHX1 (*2 and *3), MPO (*2), and NQO1 (*2) genes in 206 patients with childhood ALL and in 364 healthy individuals matched for age and gender from a Brazilian population separated by ethnicity (European ancestry and African ancestry), using the PCR-RFLP method. The CYP2D6 polymorphism variants were associated with an increased risk of ALL. The EPHX1, NQO1, and MPO variant genotypes were significantly associated with a reduced risk of childhood ALL. A significantly stronger protective effect is observed when the EPHX1, NQO1, and MPO variant genotypes are combined suggesting that, CYP2D6 polymorphisms may play a role in the susceptibility to pediatric ALL, whereas the EPHX1, NQO1, and MPO polymorphisms might have a protective function against leukemogenesis. Environ. Mal. Mulagen. 51:48-56, 2010. (C) 2009 Wiley-Liss, Inc.

Polymorphisms of xenobiotic metabolizing enzymes and DNA repair genes and outcome in childhood acute lymphoblastic leukemia

The interindividual variation in the activity of xenobiotic metabolizing enzymes and DNA repair genes could modify an individual`s risk of recurrent malignancy and response to therapy. We investigated whether ALL outcome was related to polymorphisms in genes CYP2D6. MPO, EPHX1, NQO1, TS, XPD and XRCC1 in 95 consecutive ALL children by PCR or PCR-FRLP techniques. Polymorphisms in genes NQO1 and TS were associated with a significantly slow response to induction chemotherapy and NQO1 was also associated with a lower five-year event-free survival. This study suggests that polymorphisms of NQO1 and TS could be important for patient response to induction therapy and for treatment outcome. (C) 2009 Elsevier Ltd. All rights reserved.

Polymorphisms in genes encoding drugs and xenobiotic metabolizing enzymes in a Brazilian population

Polymorphic variations of several genes associated with drugs and xenobiotic metabolism have been linked to the factors that predispose to the carcinogenesis process. As considerable interindividual and interethnic variation in metabolizing enzyme activity has been associated with polymorphic alleles, we evaluated the frequency of the polymorphisms of CYP2D6, EPHX1 and NQO1 genes in 361 Brazilian individuals separated by ethnicity (European and African ancestry), using the polymerase chain reaction-restriction fragment length (PCR-RFLP) method. The allele frequencies of the variants *3 and *4 for the gene CYP2D6 were 0.04 and 0.14 for white subjects and 0.03 and 0.10 for black individuals, respectively. For the both variants of the gene EPHX1, we found higher allele frequencies among white individuals compared with mulatto subjects (0.62 vs 0.54 and 0.18 vs 0.14, respectively); however, these differences were not statistically significant (p = 0.39 and 0.56, respectively). For the NQO1 gene we observed a higher frequency of the homozygous genotype among black individuals (7.9%) compared with white subjects (6.3%) (p = 0.003). The genotype frequencies were within the Hardy-Weinberg equilibrium. We concluded that the allele frequencies of CYP2D6, EPHX1 and NQO1 gene polymorphisms in this Brazilian population showed ethnic variability when compared with those observed in other populations.