Efficacy and safety of administering oral misoprostol by titration compared to vaginal misoprostol and dinoprostone for cervical ripening and induction of labour: study protocol for a randomised clinical trial.

BACKGROUND: Among the various methods available, the administration of prostaglandins is the most effective for inducing labour in women with an unfavourable cervix. Recent studies have compared treatment with various titrated doses of oral misoprostol with vaginal misoprostol or dinoprostone, indicating that the use of an escalating dose of an oral misoprostol solution is associated with a lower rate of caesarean sections and a better safety profile. The objective of this study is to assess which of these three therapeutic options (oral or vaginal misoprostol or vaginal dinoprostone) achieves the highest rate of vaginal delivery within the first 24 h of drug administration. METHODS: An open-label randomised controlled trial will be conducted in Araba University Hospital (Spain). Women at ≥41 weeks of pregnancy requiring elective induction of labour who meet the selection criteria will be randomly allocated to one of three groups: 1) vaginal dinoprostone (delivered via a controlled-release vaginal insert containing 10 mg of dinoprostone, for up to 24 h); 2) vaginal misoprostol (25 µg of vaginal misoprostol every 4 h up to a maximum of 24 h); and 3) oral misoprostol (titrated doses of 20 to 60 µg of misoprostol following a 3 h on + 1 h off regimen up to a maximum of 24 h). Both intention-to-treat analysis and per-protocol analysis will be performed. DISCUSSION: The proposed study seeks to gather evidence on which of these three therapeutic options achieves the highest rate of vaginal delivery with the best safety profile, to enable obstetricians to use the most effective and safe option for their patients. TRIAL REGISTRATION: NCT02902653 Available at: https://clinicaltrials.gov/show/NCT02902653 (7th September 2016).

Embolismo del líquido amniótico: caso clínico y revisión de la literatura / No disponible

El embolismo de líquido amniótico (ELA) es un síndrome poco frecuente pero con fatales resultados que se produce principalmente durante el parto o en el posparto inmediato. Se presenta un caso de una paciente de 33 años sin antecedentes médicos importantes. Coincidiendo rotura de la bolsa amniótica, comienza con sensación de mareo, que mejora con decúbito lateral izquierdo y sueroterapia. Tras el nacimiento del recién nacido, la paciente presenta parada cardiorrespiratoria de la que tras 45min de reanimación cardiopulmonar se recupera pero presenta hemorragia posparto por atonía que revierte parcialmente con la administración de metilergometrina y misoprostol ni con la colocación de balón de Bakri. Debido a la sospecha de coagulación intravascular diseminada se transfunden 8 concentrados de hematíes, 3 concentrados de plasma y 2.000 UI de octaplex; y se la traslada a la UCI de nuestro hospital con el diagnóstico de sospecha de embolismo de líquido amniótico. Al llegar a nuestro centro presenta metrorragia activa y orina hematúrica; con una hemoglobina de 7,9, trombopenia y coagulopatía, precisando transfusión de concentrados de hematíes, un pool de plaquetas, 750 cc de plasma, fibrinógeno y factor vii de la coagulación. Tras la corrección de la coagulopatía, cesa el sangrado y la paciente evoluciona, y es dada de alta a los 6 días (AU)

Amniotic fluid embolism (AFE) is a rare but fatal syndrome occurring mostly during delivery or immediately postpartum. We report the case of a 33-year-old patient with no (..) (AU)

Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features.

We investigated the aberrant promoter methylation profile of bladder cancers and correlated the data with clinicopathological findings. The methylation status of 10 genes was determined in 98 surgically resected bladder cancers, and we calculated the median methylation index (MI), a reflection of the methylated fraction of the genes tested. Methylation frequencies of the genes tested in bladder cancers were 36% for CDH1, 35% for RASSF1A and APC, 29% for CDH13, 16% for FHIT, 15% for RAR beta, 11% for GSTP1, 7% for p16(INK4A), 4% for DAPK, and 2% for MGMT. Methylation of four of the individual genes (CDH1, RASSF1A, APC, and CDH13) and the MI were significantly correlated with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern). Methylation of CDH1, FHIT, and a high MI were associated with shortened survival. CDH1 methylation positive status was independently associated with poor survival in multivariate analyses. Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in bladder cancer.

Aberrant methylation and simian virus 40 tag sequences in malignant mesothelioma.

Aberrant promoter methylation and resultant silencing of several genes plays an important role in the pathogenesis of many tumor types. We compared the methylation profile of 66 malignant mesotheliomas (MMs) and 40 lung adenocarcinomas using methylation-specific PCR for seven genes frequently methylated in lung cancer. We also compared the methylation frequencies of these genes as well as the methylation index, a reflection of all of the gene frequencies, with the presence of SV40 large T-antigen (Tag) sequences, histological subtype, and patient survival. Our major findings are: (a) with the exception of the RASSF1A promoter of the RASSF1 gene, frequencies of aberrant methylation were significantly lower in MMs than in adenocarcinomas; (b) the frequency of RASSF1A aberrant methylation and the value of the methylation index were significantly higher in SV40 sequence positive MM than in negative MM; and (c) the methylation index was higher in epithelial MM than in sarcomatous/mixed MM. Our results demonstrate a relationship between SV40 and aberrant methylation in MMs.

Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A in breast and lung carcinomas.

The adenomatous polyposis coli (APC) gene is a tumor suppressor gene associated with both familial and sporadic cancer. Despite high rates of allelic loss in lung and breast cancers, point mutations of the APC gene are infrequent in these cancer types. Aberrant methylation of the APC promoter 1A occurs in some colorectal and gastric malignancies, and we investigated whether the same mechanism occurs in lung and breast cancers. The methylation status of the APC gene promoter 1A was analyzed in 77 breast, 50 small cell (SCLC), and 106 non-small cell (NSCLC) lung cancer tumors and cell lines and in 68 nonmalignant tissues by methylation-specific PCR. Expression of the APC promoter 1A transcript was examined in a subset of cell lines by reverse transcription-PCR, and loss of heterozygosity at the gene locus was analyzed by the use of 12 microsatellite and polymorphic markers. Statistical tests were two-sided. Promoter 1A was methylated in 34 of 77 breast cancer tumors and cell lines (44%), in 56 of 106 NSCLC tumors and cell lines (53%), in 13 of 50 SCLC cell lines (26%), and in 3 of 68 nonmalignant samples (4%). Most cell lines tested contained the unmethylated or methylated form exclusively. In 27 cell lines tested, there was complete concordance between promoter methylation and silencing of its transcript. Demethylation with 5-aza-2'-deoxycytidine treatment restored transcript 1A expression in all eight methylated cell lines tested. Loss of heterozygosity at the APC locus was observed in 85% of SCLCs, 83% of NSCLCs, and 63% of breast cancer cell lines. The frequency of methylation in breast cancers increased with tumor stage and size. In summary, aberrant methylation of the 1A promoter of the APC gene and loss of its specific transcript is frequently present in breast and NSCLC cancers and cell lines and, to a lesser extent, in SCLC cell lines. Our findings may be of biological and clinical importance.

Injection locking of a 13-W cw Nd:YAG ring laser.

A lamp-pumped, 13-W cw Nd:YAG ring laser at 1.064 microm is injection locked using a 40-mW single-frequency diodelaser-pumped Nd:YAG laser as the master oscillator. The phase fidelity of the injected slave to the master is measured using an all-optical technique.