Independent clonal origin of multiple uterine leiomyomas that was determined by X chromosome inactivation and microsatellite analysis

Objective: In an attempt to clarify the clonality and genetic relationships that are involved in the tumorigenesis of uterine leiomyomas, we used a total of 43 multiple leiomyomas from 14 patients and analyzed the allelic status with 15 microsatellite markers and X chromosome inactivation analysis.Study design: We have used a set of 15 microsatellite polymorphism markers mapped on 3q, 7p, 11, and 15q by automated analysis. The X chromosome inactivation was evaluated by the methylation status of the X-linked androgen receptor gene.Results: Loss of heterozygosity analysis showed a different pattern in 7 of the 8 cases with allelic loss for at least 1 of 15 microsatellite markers that were analyzed. A similar loss of heterozygosity findings at 7p22-15 was detected in 3 samples from the same patient. X chromosome inactivation analysis demonstrated the same inactivated allele in all tumors of the 9 of 12 informative patients;. different inactivation patterns were observed in 3 cases.Conclusion: Our data support the concept that uterine leiomyomas are derived from a single cell but are generated independently in the uterus. Loss of heterozygosity findings at 7p22-15 are consistent with previous data that suggested the relevance of chromosomal aberrations at 7p that were involved in individual uterine leiomyomas. (C) 2005 Mosby, Inc. All rights reserved.

Prediction and probability of neonatal outcome in isolated congenital diaphragmatic hernia using multiple ultrasound parameters

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fetal Pulmonary Response After Fetoscopic Tracheal Occlusion for Severe Isolated Congenital Diaphragmatic Hernia

OBJECTIVE: To estimate the response in lung growth and vascularity after fetal endoscopic tracheal occlusion for severe congenital diaphragmatic hernia in the prediction of neonatal survival.METHODS: Between January 2006 and December 2010, fetal lung parameters (observed-to-expected lung-to-head ratio; observed-to-expected lung volume; and contralateral lung vascularization index) were evaluated before fetal tracheal occlusion and were evaluated longitudinally every 2 weeks in 72 fetuses with severe isolated congenital diaphragmatic hernia. Thirty-five fetuses underwent fetal endoscopic tracheal occlusion and 37 cases did not.RESULTS: Survival rate was significantly higher in the fetal endoscopic tracheal occlusion group (54.3%) than in the no fetal endoscopic tracheal occlusion group (5.4%, P<.01). Fetal endoscopic tracheal occlusion resulted in a significant improvement in fetal lung size and pulmonary vascularity when compared with fetuses that did not go to the fetal intervention (increase of the observed-to-expected lung-to-head ratio, observed-to-expected total lung volume, and contralateral pulmonary vascularization index 56.2% compared with 0.3%, 37.9% compared with 0.1%, and 98.6% compared with 0.0%, respectively; P<.01). Receiver operating characteristic curves indicated that the observed-to-expected total fetal lung volume was the single best predictor of neonatal survival before fetal endoscopic tracheal occlusion (cutoff 0.23, area under the curve [AUC] 0.88, relative risk 5.3, 95% confidence interval [CI] 1.4-19.7). However, the contralateral lung vascularization index at 4 weeks after fetal endoscopic tracheal occlusion was more accurate in the prediction of neonatal outcome (cutoff 24.0%, AUC 0.98, relative risk 9.9, 95% CI 1.5-66.9) with the combination of observed-to-expected lung volumes and contralateral lung vascularization index at 4 weeks being the best predictor of outcome (AUC 0.98, relative risk 16.6, 95% CI 2.5-112.3).CONCLUSION: Fetal endoscopic tracheal occlusion improves survival rate by increasing the lung size and pulmonary vascularity in fetuses with severe congenital diaphragmatic hernia. The pulmonary response after fetal endoscopic tracheal occlusion can be used to predict neonatal survival. (Obstet Gynecol 2012; 119: 93-101) DOI: 10.1097/AOG.0b013e31823d3aea

Avaliação do polimorfismo de grupos sanguíneos e fenótipo de hemoglobinas em um grupo de universitários de São José do Rio Preto, SP

The studies of the phenotypes of the blood groups are important for blood transfusions, for obstetrics, neonatology and law medicine, apart from its application in anthropology where it can be used as genetic markers in population studies. Works with hemoglobin polymor-phisms as a genetic marker of populations has been increased over the last few years, particularly for different population groups of Brazil. In the investigation the hemoglobin polymorphisms of 200 university students from São José do Rio Preto, Brazil were studied to establish a possible relation between the different phenotypes. Statistical analysis of the phenotypes showed that the differences observed were not significant, without a relationship among the polymorphisms of blood groups and hemoglobins.

QUANTIFICATION OF IMMUNOGLOBULIN-A IN CHORIOAMNIOTIC MEMBRANE OF PATIENTS WITH PREMATURE RUPTURE OF MEMBRANES

Objective: the proposal was to study the presence of immunoglobulin A (IgA) in the chorioamniotic membrane of healthy postpartum women with premature rupture of the chorioamniotic membrane (FROM). Method: A single radial immunodiffusion technique was used to quantify the IgA in the chorioamniotic membrane tissues. Results: the level of IgA was approximately 10 times higher in patients whose membranes had been ruptured for > 10 h (24.58 mg/dl). These results were compared with those of a previously published study where the mean of amount of IgA was 2.52 mg/dl in membranes of patients with rupture < 10 h. Our results show that IgA began to rise after 10-15 h following rupture. Conclusion: Although more studies need to be performed our data indicate that the increasing IgA in our patients after 10 h of latency probably represents the beginning of an ascending colonization of bacteria which could be the source of future infection.

Antioxidant therapy to prevent preeclampsia - A Randomized controlled trial

OBJECTIVE: To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk.METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and alpha=.05. The a level for the final analysis, adjusted for interim looks, was 0.0458.RESULTS: Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61-1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, pre-term delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79-12.62).CONCLUSION: This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among'patients with chronic hypertension and/or prior preeclampsia.

ANTS AS POTENTIAL VECTORS OF PATHOGENS IN HOSPITALS IN THE STATE OF SAO-PAULO, BRAZIL

Baiting studies performed in large, medium and small hospitals in Brazil revealed the presence of 14 ant species, with up to nine recorded in one hospital. Dominant species were exotic ants, and in the large hospital, Tapinoma melanocephalum was the most prevalent. Ants were not uniformly spread through the hospitals, but tended to be found in the more critical areas, particularly in nursery, intensive care, obstetrics, neurology and dermatology units. Bacteriological studies using specific media for bacteria associated with intra-hospital infections indicated the potential for the mechanical vectoring of species of Staphylococcus, Serratia, Klebsiella, Acinetobacter, Enterobacter, Candida and Enterococcus by ants. Although T. melanocephalum did not have the highest rate of association with these bacteria, its ubiquitous occurrences resulted in the highest overall potential as a vector of these bacteria. Because of a large number of ant species occurring in Brazilian hospitals, ants pose a potential problem to the spread of diseases in hospitals. Because of the number of associated ant species in hospitals, the control of this potential problem is much more difficult than in registered temperate areas.

Criteria for the diagnosis of diffuse uterine myohypertrophy

Objectives: Diffuse uterine myohypertrophy (DUMH) is a condition clinically diagnosed by the presence of uterine bleeding, homogeneous and diffuse uterine enlargement, and absence of any myoendometrial cause of bleeding. Since the morphologic criteria for the diagnosis of this entity are still controversial, this study aimed to investigate the clinical presentation and the morphologic findings of the cases of DUMH presenting at the University Hospital of Botucatu, São Paulo, Brazil, Methods: We retrospectively studied 43 consecutive patients with DUMH submitted to hysterectomy (test group) and compared the findings with those obtained from 28 patients submitted to hysterectomy due to a prolapsed uterus (control group). There were no significant differences in age, weight or height between the two groups. Results: the uterine weight of the DUMH group (mean +/- S.D. 157.4 +/- 46.4 g) was significantly heavier than that of the control group (99.5 +/- 35.4 g) and myometrial thickness was significantly greater in the DUMH group (2.5 +/- 0.5 cm) than in the control group (1.9 +/- 0.4 cm). No positive correlation was observed between increased uterine weight and parity, but there was a positive correlation between uterine weight and myometrial thickness. on the basis of the present study, we suggest that the diagnosis of DUMH be made clinically and in cases of uterine weight greater than or equal to 120 g and myometrial thickness greater than or equal to 2.0 cm. In addition, 10 cases of each group were analyzed by morphometry to evaluate interstitial fibrosis and myometrial hypertrophy. The data showed that the increase in uterine weight in DUMH is caused by enlargement of individual myometrial fibers rather than accumulation of interstitial collagen. Conclusion: Discriminant analysis to estimate the diagnostic significance of a number of clinical and pathologic variables (age, parity, uterine weight and morphometric parameters) was able to differentiate cases of DUMH from controls in 100% of the patients.

Bupivacaína, Ropivacaína e Levobupivacaína em Analgesia e Anestesia de Parto. Repercussões Materno-Fetais

Background and Objectives - Bupivacaine has been a very useful local anesthetic in Obstetrics in spite of its potential cardiotoxicity. In obstetric analgesia, ropivacaine is preferred to bupivacaine, and levobupivacaine is less cardiotoxic than the racemic mixture. The aim of this study was to compare the maternal-fetal effects of bupivacaine, ropivacaine and levobupivacaine in obstetric analgesia and anesthesia. Methods - Participated in this study 33 term pregnant women, physical status ASA I and II submitted to epidural anesthesia who received 18.75 mg (in 15 ml completed with 9% saline) of: GI - bupivacaine, GII - ropivacaine, and GIII - levobupivacaine. Pain intensity, sensory block level, onset time, quality of analgesia, motor block intensity, analgesia duration and time for labor resolution were evaluated. For vaginal delivery, 40 mg (in 8 ml of saline) of the same local anesthetic were used; for cesarean delivery, the dose has been mg in 20 ml solution. Newborns of these mothers were evaluated through the Apgar score in minutes 1, 5 and 10, and through the Amiel-Tison method (neurologic and adaptative capacity score - NACS) at 30 min, 2 h, and 24 h. Results - There were no significant statistical differences among groups as to sensory block level, onset time, quality of analgesia, labor analgesia duration, time for labor resolution, and Apgar scores at minute 1. Ast to motor block, GIII > GII and GI was intermediary. In relation to pain intensity, there was a trend for GI > GIII. For Apgar scores in minute 5, GII > (GI = GIII), and in minute 10 (GI = GII) < GIII. NACS at 2 h showed, GII > GI > GIII, and at 24 h, GII > GIII > GI. Conclusions - Ropivacaine has relieved maternal pain with less motor block. Newborns of GII mothers (ropivacaine) showed the best Apgar and NACS scores.

Tamoxifen down-regulates CaMKII messenger RNA levels in normal human breast tissue

Tamoxifen was proven to reduce the incidence of breast cancer by 49% in women at increased risk of the disease in the Breast Cancer Prevention Trial. In order to identify potential candidates to explain the preventive effect induced by tamoxifen on breast cancer, normal breast tissue obtained from 42 fibroadenoma patients, randomly assigned to receive placebo or tamoxifen, was analyzed by the reverse Northern blot and RT-PCR techniques. The cDNA fragments used on Northern blot membranes were generated by the Human Cancer Genome Project funded by the Ludwig Institute for Cancer Research and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil). Total RNA was obtained from normal breast tissue from patients with clinical, cytological and ultrasound diagnosis of fibroadenoma. After a 50-day treatment with tamoxifen (10 or 20 mg/day) or placebo, normal breast tissue adjacent to the tumor was collected during lumpectomy with local anesthesia. One differentially expressed gene, Calcium/calmodulin-dependent protein kinase II (CaMKII), was found to be down-regulated during TAM treatment. CaMKII is an ubiquitous serine/threonine protein kinase that has been implicated in the diverse effects of hormones utilizing Ca2+ as a second messenger as well as in c-fos activation. These results indicate that the down-regulation of CaMKII induced by TAM might represent alternative or additional mechanisms of the action of this drug on cell cycle control and response to hormones in normal human breast tissue.

Inclusion complex of S(-) bupivacaine and 2-hydroxypropyl- β-cyclodextrin: Study of morphology and cytotoxicity

Local anesthetics (LA) belong to a class of pharmacological compounds that attenuate or eliminate pain by binding to the sodium channel of excitable membranes, blocking the influx of sodium ions and the propagation of the nerve impulse. S (-) bupivacaine (S(-) bvc) is a local anesthetic of amino-amide type, widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. This article focuses on the characterization of an inclusion complex of S(-) bvc in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). Differential scanning calorimetry, scanning electron microscopy and X-Ray diffraction analysis showed structural changes in the complex. In preliminary toxicity studies, the cell viability tests revealed that the inclusion complex decreased the toxic effect (p<0.001) produced by S(-) bvc. These results suggest that the S(-) bvc:HP-β-CD inclusion complex represents a promising agent for the treatment of regional pain.