In-vitro fertilisation-embryo-transfer complicates the antenatal diagnosis of placenta accreta spectrum using MRI: a retrospective analysis.

AIM: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for the antenatal diagnosis of placenta accreta spectrum (PAS). MATERIALS AND METHODS: Data from 95 patients with placenta previa or low-lying placenta who underwent MRI at Osaka University Hospital for the antenatal diagnosis of PAS between January 2013 and December 2018 were reviewed retrospectively. The antenatal MRI signs suggesting PAS were assessed. Patients were divided into two groups depending on whether they were diagnosed with PAS. Factors that affected PAS diagnosis were identified using multivariate analysis. RESULTS: The diagnostic accuracy of MRI for detecting PAS was as follows: 71.4% sensitivity, 96.4% specificity, and area under the curve (AUC) of 0.839 (95% confidence interval [CI]: 0.73-0.91). The diagnostic accuracy was lower in patients with in-vitro fertilisation with embryo transfer (IVF-ET): 22.2% sensitivity, 93.3% specificity, and AUC=0.578 (95% CI: 0.417-0.724). On multivariate analysis, only IVF-ET showed a significant association with false-positive or -negative MRI diagnosis of PAS (adjusted odds ratio: 26.5; 95% CI: 2.42-289.4; p=0.007). CONCLUSION: IVF-ET affects the antenatal diagnosis of PAS using MRI.

Projections from the insular cortex to pain-receptive trigeminal caudal subnucleus (medullary dorsal horn) and other lower brainstem areas in rats.

This study examined the projections from the rat insular cortex (Ins) to lower brainstem areas which are possibly involved in orofacial pain processing. We first examined distributions of Ins neurons projecting directly to the trigeminal caudal subnucleus (Vc, medullary dorsal horn) and oral subnucleus (Vo) which are known to receive orofacial nociceptive inputs. After injections of a retrograde tracer, Fluorogold (FG), into the medial part and lateral part of laminae I/II of Vc, many neurons were labeled bilaterally with a contralateral predominance in the rostral level of granular Ins (GI) and dysgranular Ins (DI) and the caudal level of GI/DI, respectively, but none in the agranular Ins (AI). After FG injections into laminae III-V of Vc, no Ins neurons were labeled. After FG injections into the Vo, many neurons were labeled bilaterally with a contralateral predominance in the rostral and caudal GI/DI, but none in the AI. We then examined descending projections from the GI/DI to the lower brainstem. After injections of an anterograde tracer, biotinylated dextranamine (BDA), into the rostral GI/DI, many BDA-labeled axons and terminals were seen bilaterally with a contralateral predominance in the medial part of laminae I/II of Vc, dorsomedial Vo, juxtatrigeminal region, rostral ventromedial medulla (RVM), and nucleus of the solitary tract, and with an ipsilateral predominance in the parabrachial nucleus (Pb), Kölliker-Fuse nucleus (KF) and trigeminal mesencephalic nucleus. After BDA injections into the caudal GI/DI, they were seen bilaterally with a contralateral predominance in the lateral part of laminae I/II of Vc, ventrolateral Vo, juxtatrigeminal region and RVM, and with an ipsilateral dominance in the lateral zone (PAGl) of periaqueductal gray, Pb and KF. These results suggest that orofacial nociceptive processing of Vc and Vo neurons may be regulated by GI/DI directly or indirectly through brainstem nuclei such as PAGl, Pb, KF and RVM.

Protective effect of sulfobutyl ether beta-cyclodextrin on DY-9760e-induced hemolysis in vitro.

The hemolytic behavior of a novel cytoprotective agent, DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate) was investigated using rabbit erythrocytes. Further, the effects of water-soluble cyclodextrin derivatives, such as 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and sulfobutyl ether of beta-cyclodextrin (SBE-beta-CyD), on the hemolytic activity of DY-9760e were studied. DY-9760e induced hemolysis at concentrations >0.2-0.3 mM in phosphate buffered saline (PBS) of pH 4.0 and 6.0, where DY-9760e is predominantly in dicationic and monocationic forms, respectively. The hemolytic activity of the monocationic DY-9760e was higher than that of the dicationic species, and the hemolysis at pH 4.0 involved the formation of methemoglobin. DY9760e induced the morphological change of erythrocytes towards membrane invagination at both pH 4.0 and 6.0. SBE7-beta-CyD significantly suppressed the DY-9760e-induced hemolysis and morphological change at both pH 4.0 and 6.0, as well as the formation of methemoglobin at pH 4.0. On the other hand, HP-beta-CyD suppressed only the hemolysis, but neither the morphological change nor the formation of methemoglobin. In addition, the inhibitory effect of SBE7-beta-CyD on the hemolysis was greater than that of HP-beta-CyD. The superior inhibitory effect of SBE7-beta-CyD on the DY-9760-induced hemolysis, the morphological change, and the formation of methemoglobin may be attributable to the formation of a stable inclusion complex with DY-9760e and to the weaker hemolytic activity of SBE7beta-CyD than HP-beta-CyD. These results suggest potential use of SBE7-beta-CyD as a parenteral carrier for DY-9760e.

Influence of tooth-loss and concomitant masticatory alterations on cholinergic neurons in rats: immunohistochemical and biochemical studies.

The influence of tooth loss on the viability of cholinergic neurons was examined in rats. At 25th postnatal week, rats were divided into the three groups; a control group fed a solid diet, a soft diet group fed a powder diet and a molar crown-less group in which all molar crowns were removed and the powder diet was given. At 15 and 35 weeks post-treatment, the number of choline acetyltransferase (ChAT)-positive neurons in the nucleus of the diagonal band/medial septal nucleus (NDB/MS) was significantly smaller in the molar crown-less group than in the control group (P < 0.01). This was not the case in the pedunculopontine tegmental nucleus or (PPT) or in the trigeminal motor nucleus. Biochemical assay showed no statistically significant differences in choline concentrations in the hippocampus between the control and the molar crown-less group both at 15 and at 35 weeks post-treatment. Nevertheless, acetylcholine (ACh) concentration in the hippocampus of the molar crown-less group was significantly lower than that of the control group at 15 weeks post-treatment (P < 0.05). Taken together, a decrease of oral sensory information may have caused a reduction in the number of ChAT-positive neurons selectively in NDB/MS, which in turn caused a decline of ACh concentrations in the hippocampus.

Observation of a (6)(LambdaLambda)He double hypernucleus.

A double-hyperfragment event has been found in a hybrid-emulsion experiment. It is identified uniquely as the sequential decay of ( 6)(LambdaLambda)He emitted from a Xi(-) hyperon nuclear capture at rest. The mass of ( 6)(LambdaLambda)He and the Lambda-Lambda interaction energy DeltaB(LambdaLambda) have been measured for the first time devoid of the ambiguities due to the possibilities of excited states. The value of DeltaB(LambdaLambda) is 1.01+/-0.20(+0.18)(-0.11) MeV. This demonstrates that the Lambda-Lambda interaction is weakly attractive.

Polymeric transdermal drug penetration enhancer. The enhancing effect of oligodimethylsiloxane containing a glucopyranosyl end group.

Oligodimethylsiloxanes (ODMSs) containing a beta-D-glucopyranosyl group at one chain end (Glc-ODMSs) with various molecular weights were prepared to develop a silicone-based polymeric transdermal penetration enhancer with a non-ionic polar end group. Glc-ODMSs were prepared by hydrosilylation of hydrosilyl-terminated ODMS with 1-allyl-beta-D-glucose tetraacetate in the presence of bis(benzonitrile)platinum dichloride as the catalyst, followed by hydrolysis of the acetyl groups with sodium methoxide. The enhancing effect in the drug penetration was evaluated by in vitro experiments using a two-chamber diffusion cell. Antipyrine was used as a model drug, and the amount of drug permeating through the rat abdominal skin with or without Glc-ODMS was determined by HPLC. These enhancers were effective for the penetration of antipyrine. On the other hand, the enhancing effects were influenced by the concentration of Glc-ODMS coexisted regardless of its ODMS chain length. The enhancing effect was also observed by the pretreatment of the skin with Glc-ODMS before the drug permeation, the results of which suggested that the induction periods to appear the enhancing effects were different between Glc-ODMSs with the short and the long ODMS chain lengths. Furthermore, according to the Draize test, Glc-ODMSs exhibited no irritation to the skin regardless of the ODMS chain length.

Improvement of some pharmaceutical properties of DY-9760e by sulfobutyl ether beta-cyclodextrin.

The interaction of DY-9760e, a novel cytoprotective agent, with sulfobutyl ether beta-cyclodextrin (SBE-beta-CyD) in phosphate buffered saline (PBS) at various pH and ionic-strengths was studied by spectroscopic methods and the solubility method, and the results were compared with that of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD). The circular dichroism (CD) spectroscopic studies suggested that both beta-CyDs form the inclusion complexes with DY-9760e in a molar ratio of 1:1, and the interaction of DY-9760e with SBE-beta-CyD is much stronger than that with HP-beta-CyD at any pH studied, in terms of a synergetic effect of hydrophobic and electrostatic interactions. The different intermolecular interaction between the SBE-and HP-beta-CyD complexes was clearly reflected in the stability constant (K'), e.g. the different dependence of K' value on pH and ionic strength of solutions. 1H- and 13C-NMR studies suggested that HP-beta-CyD interacts preferably with the benzene ring of DY-9760e, whereas SBE-beta-CyD interacts not only with the benzene ring via hydrophobic interaction but also with the piperazine ring of the drug via electrostatic interaction. The solubilizing ability of SBE-beta-CyD against DY-9760e was much greater than that of HP-beta-CyD at any pH studied. Furthermore, SBE-beta-CyD markedly suppressed the photo-degradation of DY-9760e in aqueous solution and reduced the adsorption of DY-9760e from PBS to polyvinyl chloride (PVC) tubes after incubation. The results suggest that SBE-beta-CyD is useful in preparing parenteral solutions of poorly water-soluble drugs with positive charge such as DY-9760e.

Quantitative analysis of synaptic contacts made between functionally identified oralis neurons and trigeminal motoneurons in cats.

A previous study revealed that rostrodorsomedial oralis (Vo.r) neurons synapsing on trigeminal motoneurons use GABA and/or glycine as neurotransmitters. To determine the number and spatial distribution of contacts, injections of biotinamide and horseradish peroxidase were made into a Vo.r neuron and an alpha-motoneuron in the jaw-closing (JC) and jaw-opening (JO) motor nucleus, respectively, in 39 cats. All Vo.r neurons responded to low-threshold mechanical stimulation of the oral tissues. Single Vo.r neurons terminating in the JC nucleus (Vo.r-dl neurons; n = 5) issued, on average, 10 times more boutons than Vo.r neurons terminating in the JO nucleus (Vo.r-vm neurons; n = 5; 4437 vs 445). The Vo.r-dl neuron-JC alpha-motoneuron pairs (n = 4) made contacts on either the soma-dendritic compartment or dendrites, and the Vo.r-vm neuron-JO motoneuron pairs (n = 2) made contacts on dendrites, with a range of two to seven contacts. In five of the six pairs, individual or groups of two to three terminals contacted different dendritic branches of a postsynaptic cell. The Vo.r-dl neurons innervated a greater number of counter-stained motoneuronal somata than did the Vo.r-vm neurons (216 vs 26). Total number of contacts per Vo.r neuron was higher for the Vo.r-dl than Vo.r-vm neurons (786 vs 72). The present study demonstrates that axonal branches of Vo.r neurons are divided into two types with different innervation domains on the postsynaptic neuron and that they are highly divergent. The overall effect exerted by these neurons is predicted to be much greater within the JC than JO motoneuron pool.

GTP gamma S-induced Ca2+ activated Cl- currents: its stable induction by Gq alpha overexpression in Xenopus oocytes.

In native Xenopus oocytes, injection of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) (30 mM, 5 nl) did not induce Cl- current in 11 out of 22 oocytes. Injection of increased concentration of GTPgammaS (100 mM, 5 nl) into the oocytes induced Cl- currents in 16 out of 17 oocytes; however, the size of the induced currents was extremely varied. In oocytes overexpressing Gq alpha, GTPgammaS (30 mM, 5 nl) faithfully evoked Ca2+-activated Cl- currents. These results indicate that heterogeneous expression of Gq alpha in Xenopus oocytes provides a useful system for studying the functional roles of Gq alpha in regulating cellular events.

[Anesthesia for emergency surgery in a patient with Shy-Drager syndrome].

A 53-year-old man with Shy-Drager syndrome underwent emergency surgery for the resection of the larynx under general anesthesia. Anesthesia was induced with fentanyl 0.1 mg and thiopental 100 mg, and endotracheal intubation was facilitated with vecuronium 8 mg. The onset of action of vecuronium was very slow. Anesthesia was maintained with about 1% of sevoflurane, with nitrous oxide 3 l.min-1 in oxygen 3 l.min-1. Norepinephrine was effective for hypotension while dopamine was not. He was extubated on the first postoperative day without any complications. The effects of vecuronium, norepinephrine, and dopamine might be changed in the patient with Shy-Drager syndrome.

Functions of peripheral 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine4 receptor, in gastrointestinal motility.

The multiple 5-hydroxytryptamine (5-HT, serotonin) receptor subtypes are distinguished. In this article, we described mainly the 5-HT4 receptor of four subtypes of functional 5-HT receptors, 5-HT1, 5-HT2, 5-HT3, and 5-HT4, recognized in the gastrointestinal tract. In-vivo microdialysis experiments determined that activation of the 5-HT4 receptor stimulated intestinal motor activity associated with a local increase in acetylcholine (ACh) release from the intestinal cholinergic neurons in the whole body of dogs. The 5-HT4 receptor-mediated response of ACh release in the antral, corporal, and fundic strips isolated from guinea pig stomach corresponds to the presence of 5-HT4 receptor in the myenteric plexus. In-vitro receptor autoradiograms of the stomach and colon indicate that the distribution of 5-HT4 receptors in human tissues is similar to that in the guinea pig, although density of 5-HT4 receptors in the myenteric plexus of human tissues is lower than that in guinea pig tissues. The 5-HT4 receptors located in the myenteric plexus may participate in gastrointestinal motility, and thus the 5-HT4 agonists and antagonists may be available for treatment of dysfunction of gastrointestinal motility.

[A case of drug induced urolithiasis composed of acetyl sulphapyridine associated with ulcerative colitis].

A 26-year-old female visited our hospital complaining left flank pain and macroscopic hematuria. She had been suffering ulcerative colitis and administered salazosulphapyridine and predonisolone from 17-year-old. Intravenous urography showed radiolucent multiple stones in the left renal pelvis. Three sessions of extracorporeal shock wave lithotripsy were performed after ureteral stenting. Although disintegration and discharge of the stones were satisfactory, bladder stone induced by ureteral stent was complicated. The extracted bladder stone showed a yellowish brown color and the surface was granular shape. Composition of the stone was acetyl sulphapyridine which was a metabolite of salazosulphapyridine. After maintenance of the urinary pH ranges between 6.5 and 7.5 by medication of sodium bicarbonate, the patient remains free of stone for 3 years. Drug induced urolithiasis originated from salazosulphapyridine is extremely rare. Satisfactory oral fluid intake and urinary alkalization are important for prevention of sulpha drugs calculi of urinary tract.

Acute pan-costochondritis demonstrated by gallium scintigraphy.

Costochondral inflammation is a rare clinical finding. A case is presented, in which acute chostochondritis is demonstrated by gallium scinitigraphy.

Propofol inhibits muscarinic acetylcholine receptor-mediated signal transduction in Xenopus Oocytes expressing the rat M1 receptor.

The effects of propofol, 2,6-diisopropylphenol, an intravenous general anesthetic, on signal transduction mediated by the rat M1 muscarinic acetylcholine (ACh) receptor (M1 receptor) were examined in electrophysiological studies by analyzing receptor-stimulated, Ca2+-activated Cl--current responses in the Xenopus oocyte expression system. In oocytes expressing the M1 receptor, ACh induced the Ca2+-activated C1- current, in a dose-dependent manner (EC50= 114 nM). Propofol (5-50 microM) reversibly and dose-dependently inhibited induction of the Ca2+-activated Cl- current by ACh (100 nM) (IC50=5.6 microM). To determine a possible site affected by propofol in this signal transduction, we tested the effects of this anesthetic (10 microM) on the activation of current by injection of CaCl2 and aluminum fluoride (AlF4-). Propofol did not affect activation of the current by the intracellular injected Ca2+, or activation of the current by the intracellular injected AlF4-. These results indicate that propofol does not affect G protein, the inositol phosphate turnover, release of Ca2+ from Ca2+ store or the Ca2+-activated Cl- channel. Propofol apparently inhibits the M1 receptor-mediated signal transduction at the receptor site and/or the site of interaction between the receptor and associated G protein.

Physiologic and morphologic properties of motoneurons and spindle afferents innervating the temporal muscle in the cat.

Little is known about physiology and morphology of motoneurons and spindle afferents innervating the temporalis and on synaptic connections made between the two. The present study was aimed at investigating the above issues at the light microscopic level by using the intracellular recording and horseradish peroxidase or biotinamide labeling techniques and by the use of succinylcholine (SCh) for the classification of spindle afferents in the cat. Temporalis motoneurons had dendritic trees that ranged from a spherical form to an egg-shaped form. The shape deformation was more prominent for the dendritic trees made by motoneurons located closer to the nuclear border. No axon collaterals of the motoneurons were detected. On the basis of the values for the dynamic index after SCh infusion, temporalis spindle afferents were classified into two populations: presumptive groups Ia and II. The spindle afferents terminated mainly in the supratrigeminal nucleus (Vsup), region h, and the dorsolateral subdivision (Vmo.dl) of the trigeminal motor nucleus (Vmo). The proportion of group Ia afferent terminals was lower in the Vsup than that of group II afferents. In the Vmo.dl, the proportion of group Ia afferent terminals was nearly even throughout the nucleus, but that of group II afferent terminals increased in the more outlying regions. The proportion of terminal distribution in the central region of Vmo.dl was higher for group Ia than group II. The frequency of contacts (presumptive synapses) made by a single spindle afferent on a motoneuron was higher for group Ia than group II. The present study provided evidence that the central organization of spindle afferent neurons is different between groups Ia and II.

Quantitative analysis of the dendritic architectures of cat hypoglossal motoneurons stained intracellularly with horseradish peroxidase.

Little is known about the dendritic architecture of cat hypoglossal motoneurons. Thus, the present study was done to provide quantitative descriptions of hypoglossal motoneurons and to determine correlations between dendritic size parameters by using the intracellular horseradish peroxidase (HRP) injection technique in the cat. Twelve hypoglossal motoneurons stained with HRP were antidromically activated by stimulation applied to the medial branch of hypoglossal nerve. Eight (type I) and four (type II) of the 12 motoneurons were located in the ventral and dorsal parts of the ventromedial subnucleus of hypoglossal nucleus, respectively. The somatodendritic morphology of the two types of neurons was remarkably different, especially in the dendritic arborization pattern. The type I neurons established an egg-shaped dendritic tree that was distributed through the nucleus to the reticular formation; the type II dendritic tree was confined within the nucleus and presented a rostrocaudally oriented, mirror-image, fan-shape appearance. The total dendritic area and length and the number of terminations and branch points were significantly larger for type I than for type II neurons. For the two types of neuron, there was a positive correlation between stem dendritic diameter and several dendritic size parameters. Although the slopes of the regression lines were slightly different between the two, these were not statistically significant. The present study provides evidence that hypoglossal motoneurons located in the ventromedial subnucleus could be divided into two types according to the dendritic arborization pattern and quantitative analysis of the dendritic tree and according to neuronal location and suggests that the two types of hypoglossal motoneurons can be viewed as intrinsically distinct cell types: type I and type II, which innervate extrinsic and intrinsic muscles, respectively. In addition, the morphometric analysis made it possible to estimate the size of the dendritic tree by measuring the stem dendritic diameter.

De-epithelialised anterior (anterolateral and anteromedial) thigh flaps for dead space filling and contour correction in head and neck reconstruction.

Anterior (anterolateral and anteromedial) thigh flaps based on the descending branch of the lateral circumflex femoral vessels provide a long vascular pedicle and a large flap without sacrificing main vessels and muscles. Twenty-eight de-epithelialized anterior thigh flaps were transferred for reconstruction of head and neck defects following tumour ablation. Two flaps were lost in patients that had previously undergone high-dose radiotherapy following free tissue transfer. Vascularised fibula, vascularised iliac bone and other tissues were combined with anterior thigh flaps in 13 cases utilising the distal end or derivative branches of the vascular pedicle. Salivary fistula was seen in only one case, although there were many minor and major complications. In five cases, double skin flaps were harvested from the ipsilateral thigh. One of these flaps was used for coverage of intraoral defects, while the other was placed in the submandibular area to fill dead space. Compared with other methods, this multi-flap method is considered to be most suitable for dead space filling and contour correction.

Distinct roles of two separable in vitro activities of yeast Mre11 in mitotic and meiotic recombination.

UNLABELLED: In Saccharomyces cerevisiae, Mre11 protein is involved in both double-strand DNA break (DSB) repair and meiotic DSB formation. Here, we report the correlation of nuclease and DNA-binding activities of Mre11 with its functions in DNA repair and meiotic DSB formation. Purified Mre11 bound to DNA efficiently and was shown to have Mn2+-dependent nuclease activities. A point mutation in the N-terminal phosphoesterase motif (Mre11D16A) resulted in the abolition of nuclease activities but had no significant effect on DNA binding. The wild-type level of nuclease activity was detected in a C-terminal truncated protein (Mre11DeltaC49), although it had reduced DNA-binding activity. Phenotypes of the corresponding mutations were also analyzed. The mre11D16A mutation conferred methyl methanesulfonate-sensitivity to mitotic cells and caused the accumulation of unprocessed meiotic DSBs. The mre11DeltaC49 mutant exhibited almost wild-type phenotypes in mitosis. However, in meiosis, no DSB formation could be detected and an aberrant chromatin configuration was observed at DSB sites in the mre11DeltaC49 mutant. These results indicate that Mre11 has two separable functional domains: the N-terminal nuclease domain required for DSB repair, and the C-terminal dsDNA-binding domain essential to its meiotic functions such as chromatin modification and DSB formation. KEYWORDS: DNA binding/double-strand break repair/DSB formation/Mre11/nuclease

Combined anterior thigh flaps and vascularised fibular graft for reconstruction of massive composite oromandibular defects.

Six massive, composite oromandibular defects were reconstructed using combined anterior (anterolateral and anteromedial) thigh flaps and vascularised fibular graft in bridge or chimeric fashion. Except for minor dehiscence in one case and infection in another, all flaps survived without complication. Anterior thigh flaps provide large-calibre, long vascular pedicles while derivative branches from the lateral circumflex femoral system facilitate simultaneous transplantation of multiple components. Because the pedicle of the vascularised fibular graft is of insufficient length, the lateral circumflex femoral vessels provide a remote vascular source as a flow-through vascular conduit. A combined flap using the lateral circumflex femoral system is considered to be most suitable for reconstruction of through-and-through defects of the head and neck. The authors describe the advantages of this method and the detailed anatomy of the cutaneous perforators of the anterior thigh flaps.

[Management for the postoperative mediastinitis in infancy].

Postoperative mediastinitis is a rare but life-threatening complication after cardiac surgery. We successfully managed three infants with postoperative mediastinitis. When the postoperative mediastinitis was suspected, intravenous infusion of antibiotics (Vancomycin) and local irrigation were performed. The reoperation for closure was planned when the value of c-reactive protein decreased to 1.0-2.0. An application of a pectoral musculocutaneous flap was effective when the sternum was destroyed by infection.