Endoscopic closure of fetal membrane defects: comparing iatrogenic versus spontaneous rupture cases.

OBJECTIVE: Currently, physicians manage preterm premature rupture of membranes (PPROM) by expectant management or termination of the gestation. A therapy aimed at sealing membranes would be optimal to maintain the pregnancy and achieve a normal neonate. Our objective was to compare an endoscopic technique for intrauterine closure of fetal membrane defects after both iatrogenic and spontaneous rupture of membranes. METHODS: Our technique was performed on four patients experiencing PPROM spontaneously and four patients after genetic amniocentesis. Intrauterine endoscopy allowed direct visualization of membrane defects. Rapid sequential injections of platelets, fibrin glue and powdered collagen slurry were administered at the site of the defect and of trocar placement. Sonography for amniotic fluid index, nitrazine and fern testing and pad count were performed after each procedure at three intervals: immediately post-procedure, and after 24 and 48 h. RESULTS: Eight patients underwent endoscopic intrauterine sealing of ruptured membranes between 16 and 24 weeks of gestation: four were spontaneous ruptures and four were ruptures post-amniocentesis. In the post-amniocentesis group, three patients delivered viable infants at 26, 32 and 34 weeks. In one patient, the membranes ruptured again 12 h after the sealing procedure and she decided to undergo termination of pregnancy. Of the four spontaneous rupture patients, two experienced preterm labor and delivery within 2 days of the procedure. One patient was diagnosed with fetal demise 12 h post-procedure, and one patient delivered a neonate at 31 weeks of gestation with severe respiratory distress syndrome. CONCLUSIONS: This technique for sealing ruptured membranes is effective after amniocentesis, but may not be of benefit with spontaneous rupture.     

A closer look at traditional contraceptive use in Turkey.

Withdrawal is the main method used amongst couples in Turkey to prevent pregnancy. Discontinuation of use is most likely to be due to the desire to become pregnant or failure of the method. Withdrawal users are less likely to switch to another contraceptive method; however, among users who do switch, they will most likely switch to a modem method. The strongest three determinants that predict withdrawal use are using withdrawal as one's first method, the woman's age, and the husband's education. The woman's work status and the couple's ethnicity are also important predictors of withdrawal use. Family planning programs should target different segments of the population and focus on correct knowledge of all methods. Results indicate that men and women need to learn about family planning options earlier in their lives or prior to marriage.     

Emergency ligation of anomalous left coronary artery arising from the pulmonary artery

We report two cases of successful emergency ligation of anomalous left coronary artery arising from the pulmonary artery (ALCAPA) in patients with previous cardiac arrest. Both patients had regained marginal cardiac output after cardiopulmonary resuscitation and had maximal doses of inotropic support. The ALCAPA ligation was then performed as a life-saving procedure in the absence of any kind of mechanical circulatory support.     

Induction of apoptosis and cell cycle arrest by imexon in human pancreatic cancer cell lines

Imexon is an aziridine-containing small molecule currently in Phase I clinical trials. This agent has been shown to bind to thiols and increase intracellular oxidants, inducing apoptosis in hematologic cancer cells. Pancreatic cancers are known to be sensitive to oxidation, suggesting this disease may be an appropriate target for this agent. The current report examines the activity of imexon in pancreatic cells. Imexon induced concentration-dependent and time-dependent apoptosis in a panel of six human pancreatic carcinoma cell (PCC) lines. The mean IC₅₀ (SD) for growth inhibition by the SRB assay was 200 (101) µM for a 48 h exposure with a range of 64–358 µM. Cell killing was schedule-dependent, favoring exposure times ≥48 h. Imexon-treated MiaPaCa-2 cells underwent non-lethal growth arrest following exposure to concentrations ≤200 µM for 48 h. When concentrations were increased to 300 µM for ≥48 h, the MiaPaCa-2 cells arrested in G₂ phase and activated caspases 3, 8, and 9 were detected. After a 72 h exposure to the IC₈₀ concentration of imexon, cells exhibited a loss of mitochondrial membrane potential detected by CMXRos staining. However, there was no loss of reduced cellular thiols unless very high concentrations of ≥400 µM were used. In contrast, reactive oxygen species (ROS) were elevated in a dose-dependent fashion, starting at very low imexon concentrations. Imexon also significantly inhibited MiaPaCa-2 tumor growth in SCID mice at 100 mg/kg/d for 9 d. The tumor growth inhibition (% T/C) was 27% of control, and the tumor growth delay was 21 d, indicating an active agent by NCI standards. The levels of imexon that are cytotoxic in human PCC’s are achievable based on the preliminary results of the ongoing Phase I trial. Imexon appears to be active against PCCs in vitro and has an entirely novel mechanism of action involving G₂ arrest, accumulation of ROS, and the induction of apoptosis.     

Endovascular treatment of traumatic aortic rupture using iliac extension stent-grafts in patients with small aortic diameters

Open in a separate window OBJECTIVESTo evaluate outcomes after thoracic endovascular aortic repair in young patients sustaining traumatic blunt aortic injury (BAI) using iliac extension stent-grafts because of small aortic diameters measuring <24 mm.METHODSRetrospective analysis regarding clinical presentation, trauma management, endovascular techniques and outcome of patients with a small descending aorta involving an iliac extension stent-graft to treat traumatic BAI.RESULTSAmong 48 patients who suffered a BAI and underwent thoracic endovascular aortic repair, 7 received iliac extension stent-grafts. They were 27.4/[standard deviation (SD): −13.1] years old and 6 out of 7 were male. The iliac extension stent-graft was used as distal stent-graft, and a thoracic stent-graft was used in most patients as proximal extension. We achieved overall technical success in all patients during a procedure lasting 92.6 (SD: 54.9) min. One patient died 2 days after the endovascular procedure of hypoxic brain injury, and another died after 17 days of liver failure. That patient had also suffered a spinal cord injury following the procedure, as the stent-graft had been deployed in Ishimaru Zone 2, and the carotid to subclavian bypass had to be omitted because of his critical condition. Control computed tomographic angiographs was available in 6 patients after 7.7 (SD: 5.1) days and showed no endoleak. The surviving patients were discharged after 18.4 (SD: 13.4) days.CONCLUSIONSTreating traumatic BAI using iliac extension stent-grafts in young patients with small aortic diameters is feasible. We observed no mortality caused by the BAI or related to endovascular therapy within this small patient cohort.     

In vitro metabolism of etoposide (VP-16-213) by liver microsomes and irreversible binding of reactive intermediates to microsomal proteins

We have studied the metabolism of VP-16-213 (etoposide, VP-16), an antitumor agent, by mouse liver microsomes to reactive intermediates and the subsequent covalent binding to microsomal proteins. This metabolism was shown to involve the O-demethylation of VP-16 and resulted in the formation of a 3',4'-dihydroxy derivative (DHVP-16) which was identified by both HPLC and mass spectrometry. The formation of DHVP-16 was cytochrome P-450-mediated as indicated by its dependence on NADPH, its increased production following treatment of mice with phenobarbital, and its marked inhibition by SKF-525A and piperonyl butoxide. Furthermore, DHVP-16 formation required oxygen. Microsomal incubation of VP-16 resulted in an irreversible binding of the drug to the proteins, which was also shown to be cytochrome P-450 dependent. The covalent binding of the VP-16 metabolite(s) was inhibited by DHVP-16 in a dose-dependent fashion, suggesting that the reactive intermediates that bound to proteins were derived from DHVP-16. Electron spin resonance studies indicated that the same semiquinone radical was formed during enzymatic (oxidation or reduction) metabolism of DHVP-16 and the o-quinone derivative of VP-16 (VP-16-Q). VP-16-Q and its semiquinone radical are suggested to be the bioalkylating species.     

Pregnancy management for a woman with extensive vulvar and pelvic malformations caused by Klippel–Trénaunay syndrome

Klippel–Trénaunay syndrome (KTS) is a rare congenital disorder defined by a triad of capillary malformation, venous malformation, and soft tissue or bone hypertrophy most commonly affecting unilateral lower limbs. Due to the rarity of KTS, evidence‐based guidelines for the management of pregnancy in people with KTS are still lacking. A 34‐year‐old woman (gravidity 1; parity 0) presented at 25 weeks of gestation with malformations of the right side of her body. The extent of the KTS affecting the vulva, pelvis, and right leg was remarkable. As the prenatal MRI showed massive vascular malformations of the pelvis and vulva, we performed an elective cesarean section to avoid severe perinatal hemorrhage during a vaginal delivery. Intraoperatively, we observed varices on the parietal peritoneum within the vesico‐uterine pouch and the isthmocervical transition of the uterus, which were not identifiable in the preoperative MRI. Although KTS patients have been discouraged from pregnancy in the past because of a high risk for complications, successful and uncomplicated pregnancies are possible. For this purpose, we believe a multidisciplinary strategy that is crucial.     

Quantification of active ingredients in suppositories by FT‐Raman spectroscopy

An efficient method for the quantitative determination of acetaminophen (AAP) and diclofenac sodium (DS) in commercial suppositories based on partial least squares (PLS) treatment of FT‐Raman spectra is described. The relative standard errors of prediction (RSEP) were calculated for calibration and validation data sets to evaluate the quality of the constructed models. In the case of DS determination, RSEP error values of 1.9 % and 2.3 % for the calibration and validation data sets, respectively, were found. For AAP these errors amounted to 1.6–2.3 % and 1.8–2.8 %, respectively, for the different calibration models. Four commercial preparations containing 5, 12.5, 16.7 and 33.3 % (w/w) AAP and one containing 5 % (w/w) DS were successfully quantified using the developed models. Concentrations derived from the developed models correlated strongly with the declared values and yielded recoveries of 99.4–100.2 % and 99.6 % for AAP and DS, respectively. The proposed procedure can be used as a fast, economic and reliable method for quantification of the active pharmaceutical ingredients in suppositories. Copyright © 2012 John Wiley & Sons, Ltd.