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We introduced a method for producing solid phantoms with various water-to-lipid ratios that can simulate the absorption, and to some extent the scattering characteristics of human breast tissue. We also achieved phantom stability for a minimum of one month by solidifying the emulsion phantoms. The characteristics of the phantoms were evaluated using the six-wavelength time-domain diffuse optical spectroscopy (TD-DOS) system we developed to measure water and lipid contents and hemoglobin concentration. The TD-DOS measurements were validated with a magnetic resonance imaging system.

We previously compared time-domain diffuse optical spectroscopy (TD-DOS) with magnetic resonance imaging (MRI) using various water/lipid phantoms. However, it is difficult to conduct similar comparisons in the breast, because of measurement differences due to modality-dependent differences in posture. Dual-energy computed tomography (DECT) examination is performed in the same supine position as a TD-DOS measurement. Therefore, we first verified the accuracy of the measured fat fraction of fibroglandular tissue in the normal breast on DECT by comparing it with MRI in breast cancer patients (n = 28). Then, we compared lipid and water signals obtained in TD-DOS and DECT from normal and tumor-tissue regions (n = 16). The TD-DOS breast measurements were carried out using reflectance geometry with a source&ndash, detector separation of 3 cm. A semicircular region of interest (ROI), with a transverse diameter of 3 cm and a depth of 2 cm that included the breast surface, was set on the DECT image. Although the measurement area differed between the modalities, the correlation coefficients of lipid and water signals between TD-DOS and DECT were rs = 0.58 (p &lt, 0.01) and rs = 0.90 (p &lt, 0.01), respectively. These results indicate that TD-DOS captures the characteristics of the lipid and water contents of the breast.

We measured total hemoglobin concentrations in breast tumors by near-infrared time-resolved spectroscopy. Muscles interfere with measurement when the probe is close to the chest wall. Since the target area of measurement depends on the distance between the light source and probe detector, we inferred that this issue could be solved by reducing the source-detector distance. The purpose of this study was to examine the effects of the source-detector distance on the measurement of total hemoglobin concentration in the breast. We examined 26 patients with breast tumors. Total hemoglobin concentration was measured in tumors and the contralateral normal breasts at source-detector distances of 20 and 30 mm. The difference in total hemoglobin concentration between each tumor and the contralateral breast was calculated. The normal breast total hemoglobin concentration was significantly smaller for the source-detector distance of 20 mm than for the source-detector distance of 30 mm. Differences in source-detector distance did not significantly affect tumor total hemoglobin. The difference in total hemoglobin concentration between the tumor and the contralateral breast obtained at the source-detector distance of 20 mm was significantly higher than that obtained at the source-detector distance of 30 mm. From these results, we considered that measurement with a source-detector distance of 20 mm is less affected by the chest wall than with a source-detector distance of 30 mm and that the difference in total hemoglobin concentration between the tumor and the contralateral breast at a source-detector distance of 20 mm can better reflect the net total hemoglobin concentrations of the breast tumors. In conclusion, using a probe with a source-detector distance of 20 mm can more accurately evaluate the total hemoglobin concentration in breast tumors.

ADSCs(脂肪組織由来幹細胞)は再生医療において有用な細胞源であり、臨床でも応用されている。しかしながら三次元的マトリックスの足場なしでは複雑な構造の組織再生は難しく、ADSCsを用いてこのような組織再生を行なう際には足場が必要である。従来、人工足場としてはPGA不織布が汎用されているが、PGAは疎水性であるためにADSCsの接着性と増殖性が低いと考えられる。細胞接着性と増殖性を改善するために、我々はコラーゲンコーティングPGA不織布を開発した。ラットの鼠蹊部より採取した脂肪組織から得た細胞の内でフローサイトメトリーによりCD29、90が陽性かつCD 11b、45が陰性と特徴つけられる細胞群をADSCsとして実験を行った。In Vitroの細胞増殖試験で、コラーゲンコーティングPGA不織布上では、それに対応するコラーゲン非コーティングPGA不織布上よりも細胞の接着・増殖が良好であった。この結果は、コラーゲンコーティングによりPGA不織布繊維表面が親水性になり、ADSCsの接着・増殖に有利な環境に変化したためと考えられる。, Adipose-derived stem cells (ADSCs) have attracted attention as a useful cell source for tissue engineering, even in the clinical setting. However, it is difficult to regenerate tissues with complex structures in the absence of a three-dimensional matrix such as an artificial scaffold. Namely, scaffolds are required to allow implanted ADSCs to regenerate tissues with three-dimensional structures. Although non-woven PGA (poly (glycolic acid)) fabric has been used widely as an artificial scaffold, ADSCs poorly adhere to and grow on PGA fabric due to its hydrophobicity. To improve cell adhesion and growth on PGA fibers, we devised a PGA fabric coated with collagen. We isolated ADSCs from the inguinal adipose tissue of a rat and characterized the cells using flow cytometry with both CD29- and CD90-positive markers and CD11b- and CD45-negative markers. Our cell growth examination revealed that ADSC growth was improved on all of the collagen-coated fabrics compared with that observed on the corresponding non-coated fabrics. This may be because ADSCs are able to adhere and grow more readily on the hydrophilic surface of collagen-coated PGA fabrics.

膵液漏局所化のためのポリグリコール酸不織布(PGA不織布)を開発した。膵液に対する防御壁としての肉芽組織をスムーズに密に形成する足場として、3種類の足場材料を検討した。すなわちpoly (L-lactide-ε-caprolactone)コポリマーフィルム、繊維径0.9μmのPGA不織布、繊維径20μmのPGA不織布である。ラットの膵臓表面を電気メスで焼灼する膵液漏出モデルを用いた。3種類の足場材料の各1種類の材料を膵臓の焼灼された表面を覆うように周囲組織に逢着した。術後5日間、ラットの生死を観察し、5日目に剖検して肉眼的、顕微鏡的に観察した。PGA不織布の2群では、その他の2群に比べて生存率は高く、フィルム群との間で有意差を認めた。肉眼的観察では、腹水貯留、汎発性腹膜炎や腹腔内全臓器が一塊となる腫瘤形成のような重度の病理所見がみられたが、フィルム群に対してPGA不織布の2群は有意に少なかった。顕微鏡的観察では、肉芽組織は繊維径0.9と20μmのPGA不織布の全層にわたり形成され、組織障害や炎症反応は不織布外側では内側に比べ軽度であった。このようにPGA不織布では膵液漏の局所化が可能であった。対して補強なし群とフィルム群では、組織障害や炎症反応は膵臓から離れた広範囲に及んでいた。フィルム群では特に、フィルム外側でも炎症性単核細胞の集積がフィルムに沿い広がり、フィルム周囲では防御壁としての肉芽形成は乏しかった。このように補強なし群と比較しても、フィルム群では、膵液による組織損傷や炎症がより広範囲に及び、防御壁となる肉芽形成は悪かった。結論として、PGA不織布は膵液漏の治療の足場材料として有効と考えられた。, We developed sheets of non-woven poly (glycolic acid) PGA fabric that can act as a scaffold to form smoothly dense granulation tissue for barrier walls to localize leakage of pancreatic juice. In this study, we tested three kinds of materials: poly (L-lactide-ε-caprolactone) (copolymer) film, PGA fabric-0.9 with a mean fiber diameter of 0.9µm and PGA fabric-20 with a mean fiber diameter of 20 µm. Under general anesthesia, the pancreatic surface of in rats was cauterized with an electric scalpel. Then, the pancreas was wrapped with one of the three kinds of sheets and the sheet was fixed onto the surrounding tissues. Survival was observed for five days after surgery. The survival rates were higher in the two groups of fabric-treated rats than in the other groups, although the differences were significant only for the film-treated group. Macroscopically, severe pathologic findings such as accumulation of ascites, tumor formation in whole intraperitoneal organs and generalized peritonitis occurred at a significantly lower incidence in the two fabric-treated groups than in the film-treated group. Microscopically, granulation tissue was formed along the fabrics throughout the full thickness of the fabric scaffolds of fabric-0.9 and fabric-20. In these groups, injurious tissue changes and inflammatory reactions were reduced in the outer zone of the fabric wall compared to that observed in the inner zone. Therefore, the new PGA fabrics successfully localized pancreatic juice leakage. In contrast, in the no treatment group and the film-treated group, injurious tissue changes and severe inflammation were spread out to places distant from the cauterized pancreas. In the film-treated group in particular, the accumulation of mono nuclear inflammatory cells was spread along the film, even into the outer zone of the sheet, and granulation formation of a barrier wall was suppressed around the film. Therefore, in the film-treated group, tissue injury and inflammation caused by pancreatic juice extended more widely and granulation formation of a barrier wall was strongly suppressed, even compared with that observed in the no treatment group. In conclusion, these fabrics can be a more suitable and effective material for the treatment of leakage of pancreatic juice.

手術中の制御困難な出血は死亡率増加や医療費の高額化をもたらすため、術中止血は重要な課題である。そのため、多くの局所止血材が開発されている。このうちで、タココンブ(TC)は最も使用頻度が高く効果的な局所止血材の一つである。しかし、TCの優れた止血効果はヒト血液製剤と動物組織由来の止血成分を構成要素として使用されていることによる。これはTCの使用により感染症やアレルギー反応のリスクが高くなる問題を引き起こす。この問題を解決するために、アルカリ処理によりゼラチンのウイルスや抗原性構造部位ほぼ完全に排除されることに着目し、筆者らは構成要素としてアルカリ処理ゼラチンのみを使用しこれを凍結乾燥してゼラチンスポンジ作成し、これとゼラチン糊とを組み合わせた新規の止血材を考案した。スポンジ構造が傷口からの流出血液を速やかに吸収してゼラチンと粘性ゲルを形成し、同時に血中凝固成分が直ちに活性化され、その結果、出血部位で急速に血餅形成が促進される。更にゼラチン糊が血餅を含む粘性ゲルを出血部位に強固に糊着させる。本実験では(A)ゼラチンスポンジとゼラチン糊との組み合わせ、(B)タココンブ単独、(C)ゼラチン糊単独の3種類の止血材について、犬の脾臓表面を損傷させた実験モデルを用いて止血効果を比較した。その結果、ゼラチンスポンジとゼラチン糊の併用は、他の2つの材料に比較して有意に優れた止血効果を示した。結論として、ゼラチンスポンジとゼラチン糊の組み合わせは、その優れた止血効果に加えて、感染症やアレルギー反応のリスクが極めて低い利点を持つ、有用な局所止血材であることが明らかになった。, Hemostasis is a key issue in surgery because uncontrolled surgical bleeding is associated with increased mortality rates and higher costs. Many types of topical hemostatic materials have been developed. One of the most current and most effective materials is TachoComb (TC), which is reabsorbed well by conversion into connective tissue. However, TC's excellent hemostatic effects are brought about by the use of hemostatic components and a framework derived from human and animal tissues. This means that TC use is associated with a risk of infectious diseases and allergic reactions. To address the above-mentioned problems with the most current hemostatic material, we devised a new hemostatic material composed of a framework of a freeze-dried gelatin sponge combined with gelatin glue, thereby creating a new topical hemostatic material made of gelatin alone. The gelatin used in the material was prepared with alkali-treatment, and the immunogenicity and activity of viruses were eliminated almost completely. The framework absorbs blood flowing out from the wound immediately, activates autologous coagulation components in the absorbed blood and promotes blood coagulation at the bleeding site. The hemostatic effects of three types of hemostatic materials were compared, namely (A) the gelatin sponge combined with gelatin glue, (B) TC and (C) gelatin glue alone, using a dog's spleen with a shaved wound surface. Consequently, combined use of the gelatin sponge and gelatin glue exhibited significantly superior hemostatic effects to the other two materials. In the conclusion, the combination of a gelatin sponge sheet and gelatin glue is useful as a topical hemostatic material due to its superior hemostatic effects and extremely low risk of infectious diseases and allergic reactions.

To overcome the problems associated with sheet- or film-type anti-adhesive materials, we developed a new type of anti-adhesive material, gelatin flakes. We made two types of gelatin flakes with or without thermal cross-linking, and preliminarily examined their basic properties and the anti-adhesive efficacy using a rodent adhesion model. Both types of the gelatin flakes rapidly turned into gel and tightly attached the injured surfaces, absorbing the moisture and blood, when applied onto the abraded sites of rats. In addition, these flakes could be sprayed into the desired area by compressed air through a device with a long, thin tube, which could be used in laparoscopic surgery. The anti-adhesive effects of both types of gelatin flakes were similar, and both types were significantly superior compared to the non-treated group. Although further investigations are necessary, the gelatin flakes have unique and useful properties and satisfactory anti-adhesive effects, which indicate that they may be applicable in laparoscopic surgery.

Patients with bacterial endocarditis often have renal complications. This report presents the case of an elderly man with rapidly progressive glomerulonephritis (RPGN) associated with subacute bacterial endocarditis (SBE) due to Enterococcus faecalis infection. The patient was positive for anti-proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) and rheumatoid factor (RF) with hypocomplementemia. Treatment for SBE with antibiotics and the surgical replacement of the affected valves resulted in an improvement of RPGN, the disappearance of PR3-ANCA and RF, and the normalization of hypocomplementemia. This rare case suggests the importance of recognizing the cause of positive PR3-ANCA, because SBE could be an occult cause of RPGN mimicking ANCA-associated vasculitis.