Koji Kusakari

Transendoscopic projectile drug delivery.

A p r o j e c t i l e drug d e l i v e r y s y s t e m , a new e n d o s c o p i c t r e a t m e n t was d e v e l o p e d , in which s o l i d or l i q u i d d rugs were sho t t h r o u g h the e n d o s c o p e , w i t h or w i t h o u t a c a t h e t e r , to the t a r g e t u s i n g compressed a i r . h c o m m e r c i a l l y a v a i l a b l e d u s t removal c o m p r e s s e d a i r b lower was a d a p t e d f o r c o n n e c t i o n to e i t h e r the endoscope d i r e c t l y or a c a t h e t e r t h a t c o u l d be i n s e r t e d t h r o u g h the work ing c h a n n e l . The m a t e r i a l s p r o p e l l e d t h r o u g h i t c o n s i s t e d of sma l l p i l l s , p a r t i c l e s , powder and l i q u i d s . The smal l p i l l s , abou t 1 .5~1 .8 mm in d i a m e t e r , c o n s i s t e d of a c t i v a t e d carbon powder , l a c t o s e and d e x t r i n , and were sho t i n t o the g a s t r i c w a i l s of f i v e dogs . Photo 1 shows s l i g h t l y b l e e d i n g g a s t r i c mucosa 10 s econds a f t e r be ing sho t by two p i l l s wi th 40ml a i r a t a p r e s s u r e of 7 kg f / cm 2. A f t e r 2 weeks, t he t a r g e t mucosa showed s l i g h t e l e v a t i o n and r e d n e s s and a f t e r 4 weeks on ly a s l i g h t o range c o l o r was s e e n . No u l c e r f o r m a t i o n was o b s e r v e d . W h e n sma l l g r a n u l a r m a t e r i a l s ( a c t i v a t e d c a r b o n ; 40/100 mesh) were sho t i n t o c a n i n e g a s t r i c mucosa, b l e e d i n g from normal mucosa was no t r e c o g n i z e d under 3 kg f / cm 2 p r o p u l s i o n p r e s s u r e . Photo 2 shows f i n d i n g s a f t e r s h o o t i n g a n o t h e r g r a n u l a r m a t e r i a l s , s u c r a l f a t e , a t 2 k g f / c m Z ( a , no b l e e d i n g ) and 4 k g f / c m 2 ( b , b l e e d i n g ) . This sy s t em was a l s o e f f e c t i v e in p r o d u c i n g h e m o s t a s i s by i m p a c t i n g t h romb in powder on b l e e d i n g c a n i n e mucosa. The b e n e f i t s of t h i s p r o j e c t i l e d e l i v e r y sys t em i n c l u d e h igh c o n c e n t r a t i o n a d m i n i s t r a t i o n in a l i m i t e d a r e a . F u r t h e r m o r e , t h i s method can be used to i m p l a n t s l o w r e l e a s e d rugs c o n t a i n e d in a c t i v a t e d c a r b o n s f o r o p t i m a l l o c a l t r e a t m e n t . T rea tmen t by t h i s sy s t em s h o u l d be p o s s i b l e in a l l o rgans i n t o which endoscopes can be i n s e r t e d . This method h o l d s g r e a t p o t e n t i a l f o r t he t r e a t m e n t of a v a r i e t y of c o n d i t i o n s such as i n o p e r a b l e or r e s i d u a l c a n c e r ( b r a c h y t h e r a p y or s l o w r e l e a s e c h e m o t h e r a p y ) , h e m o s t a s i s , p h o t o s e n s i t i z a t i o n and e x p e r i m e n t a l c a r c i n o g e n e s i s .

Endoscopic evaluation of aceclofenac-induced gastroduodenal mucosal damage: a double-blind comparison with sodium diclofenac and placebo

Gastroduodenal mucosal damage was endoscopically compared between aceclofenac, a non-steroidal anti-inflammatory drug, and sodium diclofenac or placebo in a double-blind clinical trial. Thirty healthy male volunteers received 150 mg/ day of aceclofenac, 75 mg/day of sodium diclofenac or placebo for 2 weeks. Aceclofenac caused significantly less gastropathy than sodium diclofenac, and placebo caused no gastropathy. Both the gastric mucosal hexosamine content and gastroduodenal blood flow were significantly reduced by sodium diclofenac, while gastric mucosal hexosamine was significantly increased and gastroduodenal blood flow was unchanged with aceclofenac. Aceclofenac appears to have a low potential for causing gastroduodenal mucosal damage in humans.

Gastric Mucosal Injury by Transendoscopic Compressed Air Delivery of Powdered NaCl, KCl or NSAIDs in Dogs

Abstract: Seven kinds of NaCl, KCl, aspirin, indomethacin, diclofenac sodium, lactose and sucralfate, all in powder form, were administered by an endoscopic compressed air drug delivery system, in doses of 25 mg each, to specific target sites of the gastric mucosa of dogs. Changes in the gastric mucosa were endoscopically observed. When NaCl, KCl and aspirin were administered, mucosal lesions were observed but were limited to the target site of the gastric mucosa. Indomethacin (2/7 dogs) and diclofenac sodium (3/7 dogs) were observed to induce superficial gastritis at the pyloric antrum but did not induce gastric mucosal lesions at the target sites. In addition, no lesions were induced by either lactose or sucralfate.

A CASE OF MACROGLOBULINEMIA WITH LUNG CANCER ASSOCIATED WITH CRYOGLOBULINEMIA AND PYROGLOBULINEMIA

患者は67才,男性.老人健診の目的で来院.全身リンパ節の腫脹, X線像上,左肺上葉の円形陰影, M-蛋白を伴う高蛋白血症が発見され入院.肺異常陰影は気管支造影上B3基部の圧迫像と喀痰の細胞診でclass Vの所見から肺腫瘍と診断された.さらに,リンパ節の生検所見はリンパ球様細胞の浸潤が主体であり,また骨格ならびに他臓器の検索により原発性と考え,左肺上葉切除を行ない,組織学的に腺癌であることが判明した.その後X線像上再発を認め,骨転移による症状が出現し,放射線治療と抗腫瘍剤による治療を行なつたが間質性肺炎を合併し死亡.血清蛋白の検索から単クローンIgMの著増とλタイプのBence Jones蛋白が証明され, macroglobulin血症と診断した.さらにcroglobulinyとpyroglobulinが証明され, 1N HCl, 1N HNO3による酸-ゲル化試験でも陽性を呈した.精製したcryoglobulinはIgMとβ-lipoproteinから構成されていた.文献上肺癌とmacroglobulin血症の合併は外国では報告されているが,本邦では見当らない. macroglobulin血症とcryoglobulinならびにpyroglobulinの併存は本邦では本症例が2例目であり,本症例に該当する肺癌合併例は最初の記載と思われる.肺癌, macroglobulin血症, cryoglobulin, pyroglobulinの併存は極めて希なものであり,異常蛋白血症の病態を解明する上で貴重な症例と思われるので,臨床所見,臨床経過ならびに検査成績に剖検所見を加えて報告する.

Novel evaluation method of drug induced gastropathy using endoscopic sprayed drug delivery system.

The effect of direct irritant action of anti-inflammatory powder drugs (about 2.5mg/kg) in canine gastric mucosa studied using an endoscopic compressed air drug delivery system technique. Aspirin and loxoprofen sodium induced mucosal lesions were limited to the target site of gastric mucosa in all dogs. Indomethacin (30%) and diclofenac Na (40%) induced superficial gastritis at the pyloric antrum, but did not appear to spray sites. Mefenamic acid, ketoprofen and proglumetacin maleate did not induced mucosal lesions. Predonisolone caused the erosion and edema throughout the stomach. No lesions were induced by lactose and sucralfate.In the present study, we could observe the experimental gastric mucosal lesion at the target site of the gastric mucosa by an administration of a small amount of powdered drugs via an endoscope. The administration of powdered drugs by endoscopy is useful for the investigation of direct effects of those on the gastric mucosa.

Endoscopic study of the damaging action of diclofenac Na and prodrugs (loxoprofen Na and proglumetacin maleat) on the gastric and duodenal mucosa.

A controlled double blind study was performed for 29 healthy volunteers in order to assess the damaging action on the gastroduodenal mucosa induced by an inactive form of NSAIDs (as prodrug) in comparison with diclofenac Na (D) .Subjects received either of the following three drug combinations; (1) prodrug: loxoprofen Na, L: pro-glumetacin maleate (PGM), placebo and D: placebo, (2) prodrug (PGM) L placebo and D: placebo, (3) D, L: placebo and PGM placebo. Endoscopic findings were evaluated before and 2 weeks after drug administration. Moreover, in order to investigate the mechanism of NSAIDs gastropathy, pH of gastric juice, mucosal blood flow, levels of prostaglandin E2 (PGE2) and hexosamine (H) on biopsy specimens were simultaneously measured before and after ingestion of each medication.Gastroduodenal damages were significantly less for both prodrug group (L and PGM) compared with the D group. The enhancement of gastric acid output, decrease in mucosal blood flow and reduction of hexosamine contents were observed in D group when eompared with both prodrug group.These findings suggest that prodrugs have a very low frequency to produce mucsosal damages, and NSAIDs gastropathy might be associated with increase of offensive factor and breakdown of defensive mechanism.