Crucial factors for implementing treatment strategies in intractable atonic postpartum haemorrhage: early phase contrast medium extravasation on dynamic CT.

AIM: To identify the relationship between contrast medium extravasation (CME) on dynamic contrast-enhanced computed tomography (DCT) and clinical information in intractable atonic postpartum haemorrhage (PPH) and its relevance to treatment with uterine artery embolisation (UAE). MATERIALS AND METHODS: Of 90 patients who underwent DCT to diagnose PPH, 60 diagnosed with intractable atonic PPH were investigated retrospectively. Maternal background and clinical indicators were analysed to compare the positive and negative factors of early phase CME. Regression analysis was used to investigate the factors associated with CME. The sensitivity, specificity, and positive and negative predictive values of early phase CME for predicting UAE were calculated. Clinical outcomes were compared between the two groups according to the timing of the decision to undergo UAE. RESULTS: Of the 60 patients with intractable atonic PPH, 21 underwent UAE, 20 of whom had early phase CME on DCT. Pre-DCT clinical parameters and clinical indices were not significantly different in presence of early phase CME. Early phase CME was associated with UAE performance, with a sensitivity of 95%, specificity of 87%, positive predictive value of 80%, and negative predictive value of 97%. In cases where UAE was performed after conservative management, there was a significant increase in blood loss and transfusion volume. CONCLUSION: Early phase CME is not indicated by background factors or clinical findings. UAE is not required when CME cannot be detected in the uterine cavity. If early phase CME is present, UAE should be considered immediately.

Randomized clinical trial of landiolol hydrochloride for the prevention of atrial fibrillation and postoperative complications after oesophagectomy for cancer.

BACKGROUND: Atrial fibrillation is common after oesophageal surgery. The aim of this study was to evaluate whether landiolol hydrochloride was effective and safe in the prevention of atrial fibrillation after oesophagectomy, and to see whether a reduction in incidence of atrial fibrillation would reduce other postoperative complications. METHODS: This single-centre study enrolled patients scheduled for transthoracic oesophagectomy in a randomized, double-blind, placebo-controlled trial between March 2013 and January 2016. Enrolled patients were randomized with a 1 : 1 parallel allocation ratio to either landiolol prophylaxis or placebo. The primary endpoint was the occurrence of atrial fibrillation after oesophagectomy. Secondary endpoints were incidence of postoperative complications, and effects on haemodynamic and inflammatory indices. RESULTS: One hundred patients were enrolled, 50 in each group. Postoperative atrial fibrillation occurred in 15 patients (30 per cent) receiving placebo versus five (10 per cent) receiving landiolol (P = 0·012). The overall incidence of postoperative complications was significantly lower in the landiolol group (P = 0·046). In the landiolol group, postoperative heart rate was suppressed effectively, but the decrease in BP was not harmful. The interleukin 6 level was significantly lower on days 3 and 5 after surgery in the landiolol group (P = 0·001 and P = 0·002 respectively). CONCLUSION: Landiolol was effective and safe in preventing atrial fibrillation after oesophagectomy. Registration number: UMIN000010648 (http://www.umin.ac.jp/ctr/).

Phase I/II study of divided-dose docetaxel, cisplatin and fluorouracil for patients with recurrent or metastatic squamous cell carcinoma of the esophagus.

Squamous cell carcinoma of the esophagus (SCCE) has a poor prognosis compared with other gastrointestinal cancers. Many patients present with locoregional unresectable or metastatic disease at the time of diagnosis. For these patients with metastatic esophageal cancer, chemotherapy is generally indicated. The aim of this phase I/II study was to evaluate the efficacy and safety of the combined use of docetaxel, cisplatin (CDDP) and 5-fluorouracil (5-FU)(DCF) in patients with recurrent/metastatic SCCE. This study adopted divided doses of docetaxel and CDDP in order to reduce the toxicities of the treatment. The dose of docetaxel was escalated using the following protocol in the phase I stage: level 1, 30 mg/m2; level 2, 35 mg/m2 and level 3, 40 mg/m2, which was intravenously infused for 2 hours on days 1 and 8. CDDP was administered at a dose of 12 mg/m2 infused for 4 hours on days 1-5. The 5-FU was administered at a dose of 600 mg/m2 continuously infused from day 1 to 5. This regimen was repeated every 4 weeks. The study subjects were nine patients (phase I) and 48 patients (phase II). The recommended dose was determined as level 3 in phase I. In the phase II stage, the overall response rate was 62.5%, with a complete response rate of 12.5%. The median progression-free survival was 6 months, and the median overall survival was 13 months. Grade 3/4 toxicities of leukopenia, neutropenia and febrile neutropenia occurred in 64.6%, 68.8% and 14.6% of the patients, while grade 3/4 non-hematological toxicities were relatively rare. No treatment-related death was recorded. This modified DCF regimen with divided doses can be a tolerable and useful regimen of definitive chemotherapy for unresectable SCCE because of its high efficacy, although adequate care for severe neutropenia must be administered.

Endothelins modulate dibutyryl cAMP-induced stellation of cultured astrocytes.

Effect of endothelin-3 (ET-3) on dibutyryl cAMP (DBcAMP)-induced stellation of rat cerebral cultured astrocytes was examined. Treatment with 1 mM DBcAMP, 10 microM forskolin, 100 microM isoproterenol and 500 nM phorbol 12-myristate 13-acetate changed protoplasmic cultured astrocytes into process-bearing ones. ET-3 (1 nM) completely prevented the astrocytic stellation induced by these agents. The effect of ET-3 showed a dose-dependence, where IC50 value and maximal effective dose were 49 pM and about 0.1 nM, respectively. ET-1 and sarafotoxin (SRTX) S6b prevented the DBcAMP-induced astrocytic stellation with potencies similar to that of ET-3. ET-3 (1 nM) did not affect the cAMP accumulation after DBcAMP treatment in cultured astrocytes. Stellate astrocytes were reversed to the protoplasmic type cells by addition of 1 nM ET-3 in the presence of DBcAMP. ET-1 and SRTX similarly reversed the astrocytic stellation. ET-3 reversed the astrocytic stellation in the absence of extracellular Ca2+. Pre-loading of BAPTA-AM, a permeable Ca2+ chelator, on stellate astrocytes had no effect on the reversal by ET-3. ET-3 did not increase intracellular free Ca2+ concentration ([Ca2+]i) of most astrocytes tested at 0.1 nM. A high concentration (100 nM) of ET-3 increased astrocytic [Ca2+]i which was negated by Ca(2+)-free and BAPTA-AM loading. These results suggest that ETs modulate morphological changes in astrocytes through cAMP- and Ca(2+)-independent mechanisms.

Application of rapid and simultaneous measurement of sex steroid hormones to the monitoring of gonadotropin therapy.

A high performance liquid chromatographic (HPLC) method with both electrochemical detection (ECD) and ultraviolet spectrometric detection (UVD) was developed for the rapid and simultaneous measurement of estradiol (E2), estrone (E1), testosterone (T), 17 alpha-hydroxyprogesterone (17-OHP) and progesterone (P) in serum. These hormones were extracted with diethylether, and chromatographed on an octadecyl silane-silica (ODS) column with an eluent of a phosphate buffer solution - acetonitrile mixture (volume ratio 49:51). Estrogens were detected by ECD at +1.0 V vs. Ag/AgCl, and other hormones by UVD at 242 nm. With this method, the simultaneous determination of sex steroid hormones could be performed within approximately two hours with high precision. The hormones of 34 patients (39 menstrual cycles) undergoing human menopausal gonadotropin (HMG)-human chorionic gonadotropin (HCG) therapy were measured. It was concluded that the switch from HMG to HCG should be performed when the E2 level reaches 400 pg/ml for ovulation and 800 pg/ml for pregnancy. The occurrence of ovarian hyperstimulation syndrome (OHSS) can be predicted when the P level rises above 30 ng/ml on the 7th day after the switch. Moreover, conception may be indicated when the P level does not increase from the 7th to 14th day after the switch. In this way, this method proved to be useful for the monitoring of HMG-HCG therapy.

Rapid and simultaneous measurement of estrone, estradiol, estriol and estetrol in serum by high performance liquid chromatography with electrochemical detection.

A high performance liquid chromatographic (HPLC) method with electrochemical detection (ECD) was developed for the simultaneous measurement of estrone, estradiol, estriol and estetrol in serum. These hormones were extracted with diethylether, chromatographed on an silica-octadecyl silane (ODS) column with an eluent of phosphate buffer solution-acetonitrile-methanol (volume ratio 152:85:40), and detected by ECD at +1.0V vs. Ag/AgCl. In comparisons between the values measured by this method and radioimmunoassay, significant correlations were noted for estrone (r = 0.759, p less than 0.01), estradiol (r = 0.816, p less than 0.001) and estriol (r = 0.830, p less than 0.001). In clinical applications of this method, differences between cases of the normal and the anencephalic pregnancy in the thirty-eighth week of gestation were distinct not only in the individual estrogen, but also in the profile analysis of estrogens. With this method, all 4 serum estrogens above approximately 500 pg/ml could be measured within 2 h, and the method seemed to be clinically applicable.

[Fundamental and clinical studies of cefpimizole in obstetrics and gynecology].

The findings from recent fundamental and clinical studies of the efficacy of cefpimizole (AC-1370) in obstetrics and gynecology are reported in this paper. The AC-1370 concentrations in genital tissues sampled 30 to 56 minutes (a mean of 41.4 minutes) after intravenous injection of 1 g of the drug were 14 to 76 micrograms/g (a mean of 32.4 micrograms/g). The mean transfer ratios of the drug into the genital tissues to the concentration in the uterine arterial blood were such that the transfer ratio into the portio vaginalis was the highest, followed by the uterine cervix and the myometrium, and that into the oviduct was the lowest with about 1/2 that into the portio vaginalis. The concentration in the antecubital venous blood and that in the uterine arterial blood remained similar for all patients. The transfer of AC-1370 into the pelvic dead space exudate reached a peak (49.5 micrograms/ml) 1 hour, and also a peak (49.8 micrograms/ml) 2 hours after the intravenous injection. It then decreased gradually, but remained high, being higher than that in the antecubital venous blood about 50 minutes after the intravenous injection. Ten patients with infections in gynecology were treated with 1.0 to 4.0 g daily of AC-1370, to a total dose of 6 to 52 g, over a period of 3 to 13 days. One of them showed excellent response, 8 showed moderate response, and another showed poor response to the treatment: in other words, a response rate of 90% was achieved. Bacteriologically, pathogens were eradicated from 3 and decreased in 3, and microbial substitution occurred in another patient. No side effects of the drug were observed except for eruption in 1 patient. None of the 10 patients showed any abnormalities in laboratory findings. From the present fundamental and clinical studies of AC-1370, we have drawn the conclusion that the drug is one of extremely useful antibiotics in the treatment of infections in obstetrics and gynecology.

Diffusion theory of guided photon-density waves.

Atheoretical formulation of diffuse photon-density waves propagating in a waveguide structure, which consists of two regions with different wave speeds, is presented. In comparison with the usual optical waveguides for coherent radiation, unique features of the guided photon-density waves are found.

Algebraically decaying modes of dielectric planar waveguides.

We show analytically that, at a critical point where the effective refractive index of a mode coincides with the bulk index of a substrate region, for certain graded-index planar waveguides there exists a family of bound modes with algebraic (power-law) tails in the evanescent field.

Quasi-phase-matched multiwave mixing in a periodically poled ferroelectric crystal.

A method for realizing quasi-phase-matched multiwave mixing through second-order nonlinear susceptibilities of a periodically poled ferroelectric crystal is proposed. With an appropriate combination of light polarizations and the order of the quasi-phase-matching, all the nonlinear interactions involved are simultaneously phase matchable. Sample results predicted are shown for five-wave mixing in a periodically poled lithium niobate crystal.

Three-dimensional simulation of guided-wave second-harmonic generation in the form of coherent Cerenkov radiation.

We implement a direct three-dimensional calculation of Cerenkov-radiation-type frequency doubling in an optical channel waveguide by using a finite-element guided-beam simulator. The simulator can predict an optimum configuration and the conversion efficiency of miniaturized frequency doublers that utilize guided-to-radiation-mode interactions in nonlinear channel waveguides. Computed results are shown for blue-light generation through the frequency doubling in a proton-exchanged MgO:LiNbO(3) channel waveguide.

Self-focusing instability and chaotic behavior of nonlinear optical waves guided by dielectric slab structures.

The propagation of nonlinear optical waves guided by a nonlinear thin film bounded by two linear claddings is examined numerically. Numerical results for the propagation constant versus the propagation axis indicate that for higher-order modes the transition from periodic behavior to chaos through period doubling is observed as the guided-wave power increases, whereas for the fundamental mode an extremely stable self-focusing propagation is possible.

Multidimensional solitons in cubic nonlinear media.

We show numerically that, contrary to what has been believed so far, multidimensional optical solitons can propagate in cubic nonlinear media. To avoid a collapse along the propagation axis, we take advantage of the cross-phase modulations between fundamental- and harmonic-field components. A compact analytical expression for new solitonlike fields with an arbitrary transverse dimension is derived through a self-consistent-field approximation.

Effects of birefringence on the interaction between adjacent nonlinear pulses.

We investigate the effects of the birefringence that is latent in ordinary single-mode fibers on the interaction between two adjacent soliton pulses. Such birefringence could be induced by distortions of the core cross section along the propagation axis owing to structural imperfections or external disturbances. As the incident angle of pulses into a fiber deviates from the slow axis, the behavior of two pulses undergoes a complete change because of the combined effect of the birefringence and the cross-phase modulation. Through numerical results we conclude that the birefringence corresponding to the ordinary single-mode fiber is large enough to affect the interaction between adjacent nonlinear pulses.

Nonstationary simulation of nonlinearly coupled TE-TM waves propagating down dielectric slab structures by the step-by-step finite-element method.

Propagation phenomena of two nonlinearly coupled orthogonal waves in a slab waveguide are demonstrated numerically. It is shown that the propagation behavior is strongly dependent on the particular nonlinear mechanism as well as on the optical power allotted to each polarization component.

Cerenkov doubling of infrared radiation in a planar waveguide loaded by an organic thin film.

Frequency doubling of infrared coherent radiation in a planar waveguide loaded by an organic thin film is described. By using a strongly nonlinear crystal, such as 2-methyl-4-nitroaniline, as the loading organic material, more secondharmonic radiation can be expected than that reported in a proton-exchanged or Ti-diffused LiNbO(3) waveguide. The electromagnetic field analysis shows that the selection of a cover material that bounds the surface of the organic film is important in fulfilling the Cerenkov condition.

Corticotropin-releasing factor stimulates Ca2+ influx in cultured rat astrocytes.

Corticotropin-releasing factor (CRF) increased intracellular Ca2+ concentration in single astrocytes. The effect in increasing intracellular Ca2+ was not observed in Ca2(+)-free solution. Furthermore, CRF at concentrations more than 10 nM stimulated 45Ca2+ uptake in cultured rat astrocytes. The action was blocked by alpha-helical CRF(9-41) in a competitive manner, but not by nifedipine and 3,4-dichlorobenzamil. On the other hand, CRF did not stimulate cAMP formation, cGMP formation and phosphoinositide hydrolysis in astrocytes. These results indicate that CRF increases Ca2+ influx via an activation of CRF receptors in a cAMP-independent mechanism in cultured astrocytes.