Doxorubicin-conjugated biodegradable polymeric micelles having acid-cleavable linkages.

Doxorubicin was chemically conjugated to the terminal end of a di-block copolymer composed of poly(L-lactic acid) (PLLA) and methoxy-poly(ethylene glycol) (mPEG) via two acid-cleavable linkages. A hydrazone bond and a cis-acotinyl bond were formed between doxorubicin and the terminal group of PLLA segment in the block copolymer. Doxorubicin-conjugated PLLA-mPEG di-block copolymers self-assembled to form micelles in aqueous solution. The doxorubicin-conjugated micelles were about 89.1 nm in diameter and their critical micelle concentration was 1.3 microg/ml. These values were comparable with those of unconjugated micelles. In an acidic condition, the conjugated doxorubicin in the hydrazone linkage was readily cleaved, releasing doxorubicin in an intact structure. Doxorubicin-conjugated PLLA-mPEG micelles were more potent in cell cytotoxicity than free doxorubicin, suggesting that they were more easily taken up within cells with concomitant rapid release of cleaved doxorubicin into the cytoplasm from acidic endosomes.     

Immunoscintigraphy in the detection of tuberculosis with radiolabelled antibody fragment against Mycobacterium bovis bacillus Calmette-Guérin: a preliminary study in a rabbit model.

Immunoscintigraphy with radiolabelled monoclonal antibodies is widely used to detect solid tumours, but only a few trials have been carried out concerning the specific in vivo localization of an inflammatory process. The purpose of this study was to investigate the detectability of tuberculous foci utilizing this method with radiolabelled bacillus Calmette-Guérin (BCG)-specific F(ab')2 in rabbits. All of the tuberculous lesions (n = 8) were clearly visualized on serial scintigraphy for up to 48 h after injection of the antibody. Immunohistochemical and Ziel-Neelson staining of the tuberculous lesions confirmed the presence of the tuberculous antigens and bacilli. It failed to demonstrate any sustained retention of the BCG-specific antibody fragment in the control group with syphilitic orchitis (n = 2). Therefore, the specific in vivo localization of tuberculosis is feasible by immunoscintigraphy.     

Partial mastectomy with axillary lymph node dissection and radiotherapy as a new treatment modality of breast cancer (I).

This is the first preliminary report among two consecutive papers. Partial mastectomy(PM), axillary lymph node dissection(AD) and radiotherapy (RT) were performed on seventeen operable breast cancer patients who had been admitted from April 1991 to March 1992 to the department of surgery, Yongdong Severance Hospital for improved cosmetic appearance and better survival rate. Of seventeen patients, 47% were T1 lesion and 76% were stage I and II. Extensive intraductal component(EIC) within or around the tumor was also analyzed. Twenty nine per cent of the patients were EIC positive. The mean number of axillary lymph nodes was 21.5 after PM with AD and 20.5 after mastectomy. For radiotherapy, 4,500 rad was delivered to the breast parenchyma and 1,600 rad of boost to the primary tumor site using the electron beam method after surgery. All patients have since been living well without any local recurrence and were satisfied with breast preservation for the one-year follow-up period. We concluded that the PM, AD and RT can be another surgical treatment modality of breast cancer. A longer follow-up data will be followed on the second paper.     

Extracorporeal shock wave lithotripsy--difficulties in ESWL

At Kanbara Hospital, 187 patients with urolithiasis have been treated by extracorporeal shock-wave lithotripsy (ESWL) since the first ESWL treatment in December, 1986. Some cases in which ESWL could not be performed easily were experienced. These difficulties were analyzed retrospectively and some problems in the ESWL treatment are discussed.     

Alkaloidal components ofPanax ginseng

Over twelve alkaloids were delected in the roots ofPanax ginseng C.A. Meyer. Among them three alkaloids were isolated and were identified as N₉-formylharman, ethyl β-carboline-1-carboxylate and perlolyrine on the basis of spectroscopic studies.     

Double-bundle technique: Endoscopic posterior cruciate ligament reconstruction using tibialis posterior allograft

Recently, attention has been given to the double-bundle technique for treating the posterior cruciate ligament (PCL)-deficient knee. We present an arthroscopic PCL reconstruction using a double-bundle technique with 3-stranded tibialis posterior (TP) allograft that has not been described before. The anterolateral bundle of the PCL is reconstructed using 2-stranded TP allograft and the posteromedial bundle using 1-stranded TP allograft. Three-stranded TP allograft will be an alternative graft choice for PCL reconstruction.     

Umbilical portion of recipient's left portal vein: a useful vascular conduit in dual living donor liver transplantation for the thrombosed portal vein.

We considered performing living donor liver transplantation (LDLT) in a larger-size recipient. When the recipient was large-sized, or when the donor liver was severely steatotic or had a right-to-left volume discrepancy. We devised dual living donor liver transplantation (DLDLT) to make up for graft size insufficiency and to secure the donor's safety. However, portal vein thrombosis (PVT) presented a challenge for DLDLT because of the need for intact right and left portal veins for the implantation of both liver grafts. Our 52-year-old male patient with hepatitis B cirrhosis had suffered from repeated esophageal and gastric variceal bleeding and underwent 2 trials of a transjugular intrahepatic portosystemic shunt (TIPS). He developed TIPS occlusion and PVT involving the area just above the spleno-mesenteric confluence to the right and left PV. Also, the right PV orifice was destructed and difficult to isolate because of severe periportal inflammation and neointima growth in the TIPS mesh. The patient's two sons were inadequate for donation because of right-to-left volume discrepancy. Therefore, DLDLT using 2 left lobes was necessary to compensate for graft-size insufficiency and to secure donor safety, and we substituted an intact umbilical portion of recipient's left PV for the destroyed right PV. The patient recovered well, and liver function has been normal for more than a year. In conclusion, the umbilical portion of recipient's left PV can be a useful vascular substitute for the reconstruction of a thrombosed main portal branch in DLDLT.     

An effective pharyngoesophageal reconstruction with free radial forearm flaps

Summary Treatment of cancer of the cervical aerodigestive tract is challenging due in part to the difficulty in reestablishment of pharyngoesophageal continuity after resection of the involved tract. From May 1989 to August 1990, six patients underwent immediate reconstruction utilizing microvascular transfer of free radial forearm flaps following resection of pharyngoesophageal neoplasms. A small island flap connected to the radial vascular pedicle by fasciocutaneous branch was used to monitor the vascular condition of the hidden fabricated free forearm flap. Stricture is the most troublesome complication of esophageal reconstruction using a conventional free forearm flap. Two small triangular flaps were designed and inserted bilaterally in the distal anastomosis of both lateral esophageal walls to prevent circular contracture. The outer layer sutures were anchored to surrounding rigid structures to withstand shrinkage and circular contraction. The problem of stricture was solved by these procedures. This one-stage, easily monitored operation for pharyngoesophageal reconstruction is considered to be as useful as a free jejunal transfer.     

The mechanism of bioactivation and antigen formation of amodiaquine in the rat.

A glutathione conjugate of amodiaquine has been isolated and characterized from rat bile after administration of [14C]amodiaquine (50 mumol/kg, 5.0 muCi/rat) to anaesthetized male Wistar rats. Thioether conjugates of amodiaquine in rat bile accounted for a total of 12% of the dose, 5 hr after administration of the drug. In addition, 1% of the dose remained in the liver covalently bound to tissue proteins after 5 hr. These findings provide direct evidence that a chemically reactive metabolite, amodiaquine quinoneimine, has been formed from the drug in vivo. A second major metabolite, desethylamodiaquine, accounting for 14% of the given dose, was present in the liver after 5 hr. Enzyme inhibition studies with ketoconazole-pretreated rats showed that both amodiaquine quinoneimine and desethylamodiaquine formation can be catalysed by cytochrome P450. The demonstration that amodiaquine readily and extensively forms a metabolite in vivo, with strong reactivity towards protein and non-protein thiol groups, may help to explain the idiosyncratic toxicity observed in man.