Dehn filling trivialization on a knot group: separation and realization

Let $K$ be a non-trivial knot in $S^3$ with the exterior $E(K)$. For a slope $r \in \mathbb{Q}$, let $K(r)$ be the result of $r$--Dehn filling of $E(K)$. To each element $g$ of the knot group $G(K)$ assign $\mathcal{S}_K(g)$ as the set of slopes $r$ such that $g$ becomes the trivial element in $\pi_1(K(r))$. The purpose of this article is to prove somewhat surprising flexibilities -- a separation property and a realization property -- of the set $\mathcal{S}_K(g)$, which are refinements of the Property P in the context of Dehn filling trivialization. We construct infinitely many, mutually non-conjugate elements $g$ (in the commutator subgroup) of $G(K)$ such that $\mathcal{S}_K(g)$ is the empty set, namely, elements of $G(K)$ that survive all the Dehn fillings of $K$ whenever $K$ has no cyclic surgery. Then we prove the Separation Theorem that can be seen as a Dehn filling analogue of various separability properties of 3-manifold groups: for every non-torus knot $K$ and any disjoint finite sets $\mathcal{R}$ and $\mathcal{S}$ of slopes, there exists an element $g$ of $G(K)$ such that $\mathcal{S}_K(g)$ contains $\mathcal{R}$, but does not contain any slopes in $\mathcal{S}$ whenever $\mathcal{S}$ contains no Seifert surgery slopes. We develop this to establish the Realization Theorem asserting that for any hyperbolic knot $K$ without torsion surgery slope, every finite set of slopes whose complement does not contain Seifert surgery slopes can be realized as the set $\mathcal{S}_K(g)$ for infinitely many, mutually non-conjugate elements $g \in G(K)$. We also provide some examples showing that the Separation Theorem and the Realization Theorem do not hold unconditionally.Comment: 59 pages, 2 figure

PHARMACOKINETIC STUDY OF INTRAPERITONEALLY ADMINISTERED ETOPOSIDE AGAINST PERITONITIS CARCINOMATOSA

Etoposide is becoming important in primary and salvage therapy for ovarian cancer. In the present study, we administered etoposide (100-300 mg/subject) intraperitoneally to six patients suffering from cancerous peritonitis, particularly that resulting from ovarian cancer, to investigate the bioavailability and pharmacokinetics of this drug. The peak etoposide level in the ascites was 80 μg/ml. Twelve hours after intrapertoneal administration (i. p.), more than 10 μg/ml of etoposide was still found in ascites. The serum level after administration of 100 mg i. p. reached approximately 4 μg/ml within 30 minutes, and 1 μg/ml of etoposide was still found in serum after 24 hours. The etoposide levels in ascites and serum after 300 mg i. p. were higher than those after 100 mg i. p. When the peritoneum was intact, the area under the curve (AUC) of etoposide in ascites was low (164 μg・h/ml), and the peritoneal clearance (Clp) was high. In contrast, in advanced cancerous peritonitis, the AUC in ascites was high (500 μg・h./ml) and the Clp was low. The AUC of etoposide in the ascites of patients with cancerous peritonitis was more than five-fold greater than that of patients with an intact peritoneum, while MRT (mean residence time) was 15-fold, and VRT (variance of residence time) was 300-fold greater. The AUC ratio in intact peritoneum was 4.1, and that in cancerous peritonitis ranged from 17.8 to 27.1. AUC, MRT and VRT of etoposide transported into the blood were slightly higher in advanced cases than in those with intact peritoneum. These findings indicate that intraperitoneal etoposide han not only a direct anticancer effect in the abdominal cavity but also shows effects via the vascular system of the tumor

IN VITRO CYTOTOXICITY OF CPT-11 (SN-38) ALONE AND IN COMBINATION WITH CISPLATIN ON OVARIAN CANCER CELLS

We investigated the in vitro cytotoxic effects of CPT-11, a new derivative of camptothecin, and its metabolizable form in vivo, SN-38, on cisplatin-resistant (SHIN-3) and -sensitive (MN-1) ovarian cancer cell lines using the MTT assay. We also attempted to identify the optimal schedule of administration for cisplatin combined with low-dose continuous exposure to CPT-11 (3 μg/ml) or SN-38 (5 ng/ml). With either CPT-11 or SN-38 alone, a marked schedule-dependent inhibition of growth was obtained with exposure for over 40 hours to concentrations of those agents applicable to clinical use (CPT-11 : <7.58 μg/ml, SN-38 : <72 ng/ml), even in a cisplatin-resistant cell line. Increasing the assay AUC of these agents only by dose escalation did not enhance cytotoxity with both MN-1 (CPT-11 : 3-50 μg/ml, SN-38 : 2.16-72 ng/ml) and SHIN-3 (CPT-11 : 5-50 μg/ml, SN-38 : 21.6-720 ng/ml) cell lines up to 72 hours of exposure. Pretreatment of SHIN-3 cells with either CPT-11 (3 μg/ml) or SN-38 (5 ng/ml) for 48 hours before the administration of cisplatin (4-20 μg/ml) appeared to produce an inhibition which exceeded that produced by either a longer (96 hours) or shorter (0 hour) pretreatment with them. Flow cytometric analysis showed that treatment with CPT-11 and SN-38 in SHIN-3 cell line was associated with a peak in G₂/M phase at 24 hours and an increase in the G₀/G₁ phase fraction for up to 96 hours. It is thus suggested that the continuous administration of a low dose of CPT-11 or of SN-38 may be useful clinically. The in vitro cytotoxicity of cisplatin could be increased by pretreatment with either CPT-11 or SN-38

Endolymphatic Hydrops After Sac Surgery

Meniere’s disease is a common disease, that presents with recurrent vertigo and cochlear symptoms. The pathology of Meniere’s disease was first reported to involve endolymphatic hydrops in 1938. The endolymphatic sac is thought to have a role to keep the hydrostatic pressure and endolymph homeostasis for the inner ear. As a surgery for intractable Meniere’s disease, endolymphatic sac drainage with intraendolymphatic sac application of large doses of steroids is performed to control the endolymphatic hydrops and preserve or improve inner ear function. In the present study, to observe the effect of this surgery, we calculated the endolymphatic space size using 3-Teslamagnetic resonance imaging (MRI) 4 h after intravenous injection of gadolinium enhancement at two time points: just before surgery and 2 years after. To reveal the condition of the endolymphatic space, we constructed three-dimensional MR images semi-automatically and fused the three-dimensional images of the total fluid space of inner ear and the endolymphatic space. After fusing the images, we calculated the volume of the total fluid space and endolymphatic space. Two years after surgery, 16 of 20 patients (80.0%) showed relief from vertigo/dizziness and reductions in the ratio of the volume of the endolymphatic size to the total fluid space of inner ear. Endolymphatic sac drainage with intraendolymphatic sac application of large doses of steroids could control vertigo/dizziness and decrease the endolymphatic hydrops. These results indicate that endolymphatic sac drainage is a good treatment option for patients with intractable Meniere’s disease. In addition, volumetric measurement of inner ear volume could be useful for confirming the effect of treatments on Meniere’s disease

乳房ソナゾイド造影超音波における背景乳腺の造影効果についての検討

Purpose: The objective of this study was to retrospectively evaluate the association between background parenchymal enhancement (BPE) on contrast-enhanced ultrasound (CEUS) with Sonazoid® and patient characteristics. Additionally, background parenchymal tissues with the high-contrast effect were pathologically observed compared to those showing the low-contrast effect. Methods: A total of 65 patients who underwent breast CEUS with Sonazoid® between January 2010 and November 2013 were enrolled. Regions of interest (ROIs) were put on the tumor and on the background parenchymal tissue. The dB values during the nonenhanced time and at peak contrast enhancement were measured based on the time intensity curve (TIC) drawn by the ROI. The differences in the dB values of pre- and post-enhanced time were obtained separately for ROIs on the tumor and ROIs on the parenchymal tissue. The patient characteristics studied were age, menstrual status, mammographic density, BPE on magnetic resonance imaging (MRI), and pathological diagnoses of breast tumors. Results: There was a weak negative correlation between BPE on CEUS and age. As for the contrast effect of parenchymal tissue, there was a significant difference between the menstruating and menopausal groups. There was no significant difference among the levels of mammographic density, and among the degrees of contrast effect on MRI. BPE on CEUS was the same between those with a malignant tumor and those with a benign tumor in each menstrual status. The parenchymal tissue with the low-contrast effect showed pathological atrophy. Conclusion: The degree of BPE on CEUS appeared related to age, menstruating or menopausal, and atrophy of breast tissue. BPE on CEUS was the same between those with a malignant tumor and those with a benign tumor in each menstrual status.博士（医学）・乙第1508号・令和3年3月15日© Springer Nature Singapore Pte Ltd. 2020.© The Japan Society of Ultrasonics in Medicine 2020.This is a post-peer-review, pre-copyedit version of an article published in Journal of medical ultrasonics. The final authenticated version is available online at: https://doi.org/10.1007/s10396-020-01052-4

新規な磁気共鳴イメージングを用いたメニエール病の高精度診断法

Background: Pathologically, Meniere's disease symptoms are considered to be associated with endolymphatic hydrops. Examinations revealing endolymphatic hydrops can be useful for accurate Meniere's disease diagnosis. We previously reported a quantitative method for evaluating endolymphatic hydrops, i.e., by measuring the volume of the endolymphatic space using three-dimensional magnetic resonance imaging (MRI) of the inner ear. This study aimed to confirm the usefulness of our methods for diagnosing Meniere's disease. Here, we extracted new explanatory factors for diagnosing Meniere's disease by comparing the volume of the endolymphatic space between healthy volunteers and patients with Meniere's disease. Additionally, we validated our method by comparing its diagnostic accuracy with that of the conventional method. Methods and Findings: This is a prospective diagnostic accuracy study performed at vertigo/dizziness centre of our university hospital, a tertiary hospital. Eighty-six patients with definite unilateral Meniere's disease and 47 healthy volunteers (25 and 33 males, and 22 and 53 females in the control and patient groups, respectively) were enrolled. All participants underwent 3-Tesla MRI 4 h after intravenous injection of gadolinium to reveal the endolymphatic space. The volume of the endolymphatic space was measured and a model for Meniere's disease diagnosis was constructed and compared with models using conventional criteria to confirm the effectiveness of the methods used. The area under the receiver operating characteristic curve of the method proposed in this study was excellent (0.924), and significantly higher than that derived using the conventional criteria (0.877). The four indices, sensitivity, specificity, positive predictive value, and negative predictive value, were given at the threshold; all of these indices achieved higher scores for the 3D model compared to the 2D model. Cross-validation of the models revealed that the improvement was due to the incorporation of the semi-circular canals. Conclusions: Our method showed high diagnostic accuracy for Meniere's disease. Additionally, we revealed the importance of observing the semi-circular canals for Meniere's disease diagnosis. The proposed method can contribute toward providing effective symptomatic relief in Meniere's disease.博士（医学）・甲第807号・令和3年12月21日Copyright © 2021 Ito, Inoue, Inui, Miyasaka, Yamanaka, Kichikawa, Takeda, Kasahara, Kitahara and Naganawa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms