犬の椎間板内への注入により生ずるChemonucleolysisの経過をX線学的ならびに組織学的に観察した. 注入によりX線学的に狭小化を示した椎間板腔は2週目より徐々に回復を示し, 12週目には0.1mg例で74.1%, 1.0mg例で61.1%および10.0mg例で71.7%まで回復していた. また, 加齢により回復が遅延する傾向がみられた. 組織学的には, 注入2週目には椎間板腔が減少を示し, 投与酵素量に応じてプロテオグリカン陽性基質が減少していた. 髄核は増殖軟骨細胞とコラーゲン基質で囲環された不整形の変性脊索細胞塊より成っていた. 12週目には, 髄核中心は線維軟骨組織に置換されていた. 10.0mg例では椎間板腔は変性基質を伴わない密な軟骨組織で満たされ, 椎間板腔が狭小化していた. これらの結果より, 10.0mgによるChemonucleolysisは化学的椎間板減圧術として犬の椎間板内圧を減少させ, 椎間板ヘルニアの病状を軽減すると考えられる.

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We investgated the changes of proteoglycan (PG) structure in chemonucleolysis using an electron microscope. Dehydration was used before embedding N-N-dimethylformamide (DMF) but not ethanol. Two Kinds of filaments were identified in the extracellular matrix of a normal rabbit's intervertebral disc except for collagen fibers. The small filaments had disappeared in the nucleus pulposus three hours after injecting chymopapain. The large filaments had disappeared and the small ones changed in the nucleus pulposus three hours after injecting hyaluronidase. As chymopapain is a cysteine protease, it affects the protein component of PG. Hyaluronidase affects a hyaluronic acid and glycosaminoglycans of the PG monomer. We assumed that the small filament is a PG monomer and the large one is a hyaluronic acid. Chymopapain digests proteins of the PG monomer, so the PG looses water and its network of collagen fibers.

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The effect of chymopapain treatment on the rabbit intervertebral disc was studied in vivo. Different doses of chymopapain (0.3 to 80pKunits/10μl) were injected into the intervertebral disc of 18 Japanese white rabbits. One week after injection, disc heights had decreased in the groups receiving 2.5 pKunits/10μl or more. Twelve weeks after injection, disc heights had recovered only in the group receiving 2.5pKunits/10μl. Histologically, only 2.5pKunits/10μl injected discs showed disc regeneration. The loss of safranin-O staining was observed in the groups injected with 5pKunits/10μl or more chymopapain, and a large defect in the bony end-plate was seen in the discs injected with over 20pKunits/10μl. It was concluded that disc regeneration depends upon the dose of injected chymopapain. Also clinically, more desirable results may be expected by control of the injection dose.

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Twenty-four patients operated for lumber disc herniation and five patients treated with chymopapain injection were studied to evaluate the effectiveness of magnetic resonance (MR) imaging in investigating postoperative disc degeneration and disc herniation. After operation in 9 patients compressed dura was present, after chymopapain injection in one patient. After operation in 6 patients the progress of disc degenerati on waspresent. In patients with chemonucleolysis changes of MR findings correlated histological reports, which may show the reconstruction of disc, while postoperative MR findings and clinical findings did not correlate.

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Five patients treated with chymopapain injection was evaluated by clinical, radiological and MRI method. The mean age was 34.6 years. Four of them had satisfactory results but recurrent pain resulted in one case. Clinical outcome by Japanese Orthopaedic Association (J. O. A.) score after 12 months was 73.9%. Disc space height was gradually decreased except for one case. Disc herniation was observed to gradually diminish in size for 4 cases, whereas disc bulging resulted in one acute disc height decrease. As the result, it was confirmed that degree of disc degeneration might be related to disc space height after chemonucleolysis and to be important to judge which disc herniation segment was dissolved by chymopapain. It seemed that discography and MRI were most excellent preinjection examination.

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腰痛の分節不安定性が慢性腰痛の原因として想定されているが, その症候, X線所見については明確でない.慢性腰痛患者のX線所見に不安定性を示す特徴的所見が存在するかどうかを知る目的で, 1988年のある期間に外来受診した患者の5年後の予後調査で慢性腰痛群26例と急性腰痛群30例を選び, その2群間に以下の10項目のX線所見に出現頻度に差があるかどうかを調べた.椎間腔狭小 (P=0.001), Traction Spur (P=0.01), 椎間腔楔状化 (p=0.03), 側彎 (p=0.02) は有意に慢性腰痛群に多く, Claw Spur, たり (前方, 後方, 側方), 椎間腔後方開大, 終板下骨硬化には有意な差がみられなかった.前4項目のX線所見は腰椎不安定性を示す特徴的所見の可能性がある.

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To confirm the effect of laser nucleotomy on intradiscal pressure decrease, the relation between IDP and vertical load was measured and a new type needle for preventing the complications by the heat was developed.
The IDP was measured by pressure transducer with increasing vertical load for following three groups of rabbits' lumbar discs. 1) normal discs, 2) conventional intradiscal nucleotomy, 3) laser nucleotomy. The curves of the IDP of laser nucleotomy was almost same with that of conventional intradiscal nucleotomy.
Using a usual spinal needle, the quarts fiber and needle were often damaged by burn back and the heat injury of the tissue around the tissue was often occurred. To prevent these complications, a new type needle with Teflon coated double lumen and a connector for aspiration was developed. The needle could solved these problems.
Laser nucleotomy suggested to be applied clinically by its easiness and safety.

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2018年から保険適応となった腰椎椎間板内ヘルニアに対する椎間板内酵素注入療法の治療成績報告は未だ少ない．当院での椎間板内酵素注入療法の短期経過を報告する．症例は従来の保存的治療に抵抗性の腰椎椎間板ヘルニア患者で，術後3ヶ月以上経過観察できた6例である．平均年齢は48.5歳，男性5例女性1例，ヘルニア高位はL4/5が2例，L5/Sが4例，穿刺はいずれも患側から行った．重篤な副作用はなく，3ヶ月後のMRIでヘルニア塊の消失が1例，縮小が2例，不変が3例だった．ヘルニア内にT2高信号領域があった2例では消失もしくは縮小した．Pfirrmann分類や穿刺針先位置で有意差はなかった．観察期間が3ヶ月と短期であるが，本治療法は腰椎椎間板ヘルニアの手術回避へ向けた有用な方法であると考える．

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Functional magnetic resonance imaging (fMRI) is expected as a biomarker of pain because it can objectively evaluate changes in cerebral blood flow associated with neuron activity against pain. We have developed pain models for cynomolgus macaques because it is more compatible with humans in regard to the structures and functions of brain regions which is suggested to be involved in pain in humans. Aside from humans, the cynomolgus macaques are the most widespread primate genus, ranging from Japan to North Africa. Since the macaques are the animal species closest to humans among those which can be used for invasive experiments, they are widely used to understand the mechanisms of the human brain. The purpose of this study is to elucidate pain–related brain activation regions in the macaque models using fMRI. Generally, pain testing in animal models has been based on avoidance behavior against pain stimuli. However, we identified pain–related brain activation regions using fMRI under propofol anesthesia as a more objective evaluation method. In the macaque model of chymopapain–induced discogenic low back pain, the activity of the insular cortex occurred in response to lumbar compression stimulation. In the macaque model of oxaliplatin–induced neuropathic cold hypersensitivity, activation of the insular cortex also occurred in response to cold stimuli. As a result of evaluating pregabalin, duloxetine and tramadol, only duloxetine showed behavioral effectiveness and suppressed activation of the insular cortex due to oxaliplatin–induced neuropathic pain. In the macaque model of postoperative pain, activation of the insula cortex was mainly activated by pressure stimulation. As a result of evaluating morphine, pregabalin and diclofenac, only morphine showed behavioral effectiveness and suppressed activa­tion of the insular cortex due to postoperative pain. However, macaques with naturally occurring endometriosis exhibited a pain response against pressure stimuli to the abdomen, and had activation of the thalamus. As a result of evaluating morphine, meloxicam and acetaminophen, only morphine showed behavioral effectiveness and suppressed activation of thalamus due to abdominal pain from endometriosis. It was suggested that the brain activation regions could change due to various conditions that can cause the pain, as the acute pain increased activation in the insula cortex and the chronic pain increased activation in the thalamus. This study demonstrated the usefulness of fMRI as a pain biomarker, and fMRI analysis using the macaques might provide an advantage for the translation of the findings to human patients. Therefore, these study will contribute to the development of new analgesics for each pain as well as to the progress in the areas of brain research.

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  Introduction : Condoliase injection for lumbar disc herniation is less invasive than surgical treatment and has been widely used in recent years. We encountered a case in which a herniated disc worsened after treatment with condoliase (Hernicore^®) injection. Thereafter discectomy was performed. We also report the pathology of the disc removed immediately after condoliase injection.

  Case presentation : A 34-year-old man with a history of lumbago and left lower extremity pain for 6 months presented to another hospital, wherein magnetic resonance imaging (MRI) showed subligamentous extruded type L5-S1 disc herniation. The patient underwent condoliase injection 3 months after the first visit. However, the patient’s symptoms worsened on the second day after condoliase therapy and did not improve despite the nerve block. MRI showed a transligamentous extrusion-type hernia and substantial compression of the dural sac.

  Course of treatment : After admission to our hospital, although the patient was administered pregabalin and tramadol, there was no improvement : his preoperative Japanese Orthopaedic Association (JOA) lumbago score was 9/29. Seventeen days after condoliase injection, discectomy was performed to remove the sequestrated herniation. The ventral side of the dural sac was strongly adhered to the disc space. Postoperatively, the patient’s left lower extremity pain improved. However, his lumbago persisted, with a postoperative JOA lumbago score of 15/29. Postoperative MRI revealed Modic type 1 changes in the L5/S1 intervertebral space. His lumbago improved 2 months after surgery, and the Modic type 1 changes disappeared 5 months after surgery.

  Pathological findings : We compared the excised herniated disc with four aged-matched surgical control cases without condoliase treatment. Toluidine blue staining showed that glycosaminoglycans were substantially decreased in the condoliase-treated discs compared with the control discs. No histological changes in structure were observed.

  Discussion : In clinical trials, surgery was still required in approximately 10% of cases after condoliase treatment. However, early deterioration after treatment is rare. The pathological findings in the present case indicated that the glycosaminoglycans in the intervertebral disc were degraded early after condoliase administration. Due to the prolonged postoperative lumbago, we considered the possibility of condoliase-induced tissue damage in addition to bacterial discitis.

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腰椎椎間板ヘルニアに対するコンドリアーゼ注入療法は手術と保存的治療の中間治療として期待されている．東京医科歯科大学整形外科協力関連施設の5施設で2018年9月より神経根症性疼痛を主体とした腰椎椎間板ヘルニアに対してコンドリアーゼを用いて椎間板内酵素注入療法を積極的に行ってきた．投与後半年以上フォローが可能であった124例を調査したところ，97例（78.2％）において下肢痛が半減し，6ヶ月以内に6例（5％）がヘルニア摘出術を受けた．8例に軽度の急性期合併症が見られた．下肢痛半減までの期間は，1ヶ月以下が41.5％，1～3ヶ月が36.9％，3～6ヶ月が15.4％，6～12ヶ月が6.2％であり多くは3ヶ月以内に改善することが分かった．

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コンドロイチナーゼABC-I（cABC-I）は、コンドロイチン硫酸（CS）を分解する酵素として、長年にわたり研究されてきた。CSには複数の異性体が存在し、cABC-Iとの反応性もCS異性体ごとに異なる。本稿では、最新の知見として、構造均一性を高めたCSに対するcABC-Iの反応性、及びcABC-IとCS由来の不飽和二糖との複合体の結晶構造解析の結果に基づいて、cABC-Iの基質特異性について概説する。

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A nylon-wool bag for the large-scale depletion of monocytes to obtain high purity and high yeild selection of human CD34 positive cells in mobilized blood was newly developed. The bag was made of a blood transfusion bag containing a nylon-wool which were treated with human gamma grobulin. After double treatment with the bags, 98.4% (n=4) of monocytes were depleted from mobilized peripheral blood. However, 74.9% of the CD34 positive cells were recovered. After the depletion of monocytes, immunomanetic separation system was used to collect CD34 positive cells. CD34 positive cell purities were increased from 12.6% preseparation to 94.0% postseparation with a mean yield of 54.1%. Fourty-one pint five percent of CD34 positive cells could formed blood cell clones in the presence of growth factors by single cell culture method. Fourteen percent of these clones proliferated to over 10⁵ cells, and 9.4% of the clones contained megakaryocytes.

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はじめに：コンドリアーゼ椎間板内注入療法による椎間板や椎体終板への影響を定量的に評価した報告は渉猟し得た限りない．

対象と方法：コンドリアーゼ椎間板内注入療法を施行し1年後までMRI UTE法を施行した11例を対象とした．椎間板と椎体終板の評価をそれぞれPfirrmann分類，End Plate Classification and Scoreで分類し，椎間板髄核と椎体軟骨終板のT2＊値を計測した．椎間板高の計測およびModic changeの有無も評価した．

結果：椎間板髄核T2＊値は治療後に8例が短縮し，治療後3週から3ヶ月で再延長していた．椎間板高は治療後に低下し，8例が治療後3ヶ月から1年で軽度回復していた．治療後1年で椎間板高が低下した割合と，治療前椎間板髄核T2＊値の間で負の相関を認めた．椎体軟骨終板T2＊値は治療後6ヶ月から1年で変化が見られた．

結語：コンドリアーゼ治療後に椎間板の水分量が低下するものは軽度回復し，その後椎間板高も軽度回復していた．椎体軟骨終板の変化はコンドリアーゼによる直接的な影響ではなく椎間板変性による結果と考えられた．

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