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

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

Three-Dimensional Magnetic Resonance Imaging Reveals the Relationship Between the Control of Vertigo and Decreases in Endolymphatic Hydrops After Endolymphatic Sac Drainage With Steroids for Meniere's Disease

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-Tesla magnetic 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

Studies on Hypoplastic Anemia (panmyelopathy); (Mainly depending on our departmental experiences)

In Japan, hypoplastic anemia has ever been presenting one of the most important problems among today's anemic diseases, it having proved as great frequency as that of pernicious anemia found both in Europe and America; besides, no fit therapeutic method been discovered as yet. Generally speaking, this disease shows a decrease of entire corpuscles, the bleeding tendency becoming prevalent in most cases; yet as to signs in concern to bone marrow, the number of nuclear cell is not fixed, as it has proved 16, 200 at the lowset, while, 263, 000 at the highest. Consequently, it has been classified into 5 types in our department, in view to obstructions of bone marrow. 1. Type of bloodcell-arrest. 2. Type of maturation-arrest. 3. Type of disturbanced regeneration. 4. Mixed type. 5. Panmyelophthisis. When we took record about 23 cases of hypoplastic patients, results were as follows; 1st type 7, 2nd type 2, 3rd type 3, 4th type 8, and 3 cases of 5th type. In all serum iron value proved an increase; in view to intravenous iron tolerance test, the degree of iron disappearance proved a marked delay, while hematopoetic function indicated an extreme decline. In tissue culture of bone marrow invented by our department. it has been recognized that there exists certain factor to inhibit any hyperplasia of parencyma of bone marrow in this anemic serum. As for method in therapy, several have been nominated through in vain, so that more or less effect have been achieved only by our inventions, i.e., imbedding of bone marrow as well as use of substances of polysaccharide extracted from bone marrow

Studies on the effect of the nutrient vessels of the bone-marrow upon the bone-marrow circulation Part 3: The change in point of the time of the bone-marrow circulation caused by ligating the principal nutrient vessel of a rabbit femur

In investigating how long it takes the bone-marrow circulation to recover after the ligating of the principal nutrient vessel of a rabbit femur with Radioisotope P(32) as a tracer, the following results were obtained. 1) When the principal nutrient artery of a fully grown rabbit is ligated, the bone-marrow circulation is about 20% of control within the lapse of one day, but the recovery by the collateral circulation is by degrees seen and the complete recovery is realized in one month. But some recovers rather more quickly, the other slowly, by each individual difference. 2) When the principal nutrient artery of a young rabbit femur is ligated, the recovery of the bone-marrow circulation is rather slow than that in the case of a fully grown rabbit. That is to say, the connection of the principal nutrient artery with the other nutrient artery in a young rabbit is worse than that in the case of a fully grown rabbit. 3) When the principal nutrient vessel of a fully grown rabbit femur is ligated, the bone-marrow stagnation recovers in the early stage. This is caused by the same reason as that expressed in the 3) item of the part 2

Studies on the effect of the nutrient vessels of the bone-marrow upon the bone-marrow circulation Part 2: The blood-supplying percentage of the nutrient vessels of a rabbit femur upon the bone-marrow circulation

After investigating how the nutrient vessels distributed in a rabbit femur control the bone-marrow circulation with Radioisotope P(32) as a tracer, the following results were obtained. 1) The difference of the blood quantity supplied into both femur marrows from the nutrient arteries is within 4%. 2) Observing the controlling state of the bone-marrow circulation of the nutrient arteries, the controlling power of the principal nutrient artery is 79%, the greatest percentage of all. Next, that of the periosteal artery is 14%, and that of the vessels in the metaphysis and diaphysis is 7%, being of the least significance. 3) When the principal nutrient vein is ligated, the bone-marrow stagnation is very slight. This is because the veins except the principal nutrient one are better developed than the arteries except the principal nutrient one, and the bone-marrow, being contained in bone, is difficult to increase in the volume

CD98 heavy chain protein is overexpressed in non-small cell lung cancer and is a potential target for CAR T-cell therapy

Abstract Chimeric antigen receptor (CAR) T cells are effective against hematological cancers, but are less effective against solid tumors such as non-small cell lung cancer (NSCLC). One of the reasons is that only a few cell surface targets specific for NSCLC cells have been identified. Here, we report that CD98 heavy chain (hc) protein is overexpressed on the surface of NSCLC cells and is a potential target for CAR T cells against NSCLC. Screening of over 10,000 mAb clones raised against NSCLC cell lines showed that mAb H2A011 bound to NSCLC cells but not normal lung epithelial cells. H2A011 recognized CD98hc. Although CAR T cells derived from H2A011 could not be established presumably due to the high level of H2A011 reactivity in activated T cells, those derived from the anti-CD98hc mAb R8H283, which had been shown to lack reactivity with CD98hc glycoforms expressed on normal hematopoietic cells and some normal tissues, were successfully developed. R8H283 specifically reacted with NSCLC cells in six of 15 patients. R8H283-derived CAR T cells exerted significant anti-tumor effects in a xenograft NSCLC model in vivo. These results suggest that R8H283 CAR T cells may become a new therapeutic tool for NSCLC, although careful testing for off-tumor reactivity should be performed in the future