Pancreatic diseases: evaluation with MR cholangiopancreatography.

Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive diagnostic modality capable of producing high-quality images of the biliary tree and pancreatic duct. We evaluated the MRCP capability of depicting the normal pancreatic duct and, based on data achieved, studied the usefulness in the pathologic pancreatic duct. MRCP was performed in 42 patients without any pancreatic lesion and in 162 patients with pancreatic diseases, including congenital anomalies of biliary tree and pancreatic duct. Results were compared with endoscopic retrograde cholangiopancreatography (ERCP) in 93 patients. The visualization of the pancreatic duct and its branches and the presence or absence of dilatation, stenosis, and filling defects were recorded. All images were interpreted retrospectively and blindly by three radiologists. Among control patients, the main pancreatic duct (MPD) was depicted in the head, body, and tail of the pancreas in 41 (98%), 39 (93%), and 31 (74%), and accessory pancreatic duct and secondary branches in the head, body, and tail of the pancreas were depicted in 11 (26%), eight (19%), four (10%), and two (5%) of these patients. Compared with ERCP, MRCP overestimated the stenosis of MPD and underestimated the dilatation of the branches and filling defects in the pancreatic duct in pancreatic diseases, especially pancreatitis. However, MRCP was distinctly advantageous over ERCP in diagnosing mucin-producing tumor of the pancreas, cystic lesions, and depicting the whole, including the part distal to the obstructed site. Four of the eight cases of pancreas divisum, and 10 of the 12 cases of anomalous pancreaticobiliary duct union also were demonstrated. MRCP can accurately demonstrate the normal pancreatic duct as well as various pancreatic duct abnormalities, including congenital anomalies of the biliary tree and pancreatic duct.

Bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type.

PURPOSE: To report a patient with bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type. METHODS: Case report. RESULTS: A 55-year-old woman complained of visual field loss and decreasing vision. Seven months earlier, uterocervical carcinoma of the squamous cell type was diagnosed and treated with chemotherapy and irradiation. Serous retinal detachment and choroidal masses were present in both eyes. Retinal detachment was lessened in both eyes after radiotherapy. The patient died of respiratory insufficiency 3 months after the appearance of choroidal metastases. At autopsy, there was no second cancer to cause the choroidal metastases. Tumor embolization was present in the choriocapillaries. CONCLUSION: Choroidal metastasis may develop from hematogenous spread of uterocervical squamous cell carcinoma.

Synthesis of Cycleanine Mono-N-oxides

Oxidation of cycleanine (3) with m-chloroperbenzoic acid gave two diastereomeric N-oxides (1 and 2), and their stereochemistry was unambiguously determined on the basis of spectroscopic evidence. The NMR spectra of synthetic cycleanine mono-N-oxides 1 and 2 were significantly different from those of the natural product previously reported to be cycleanine N-oxide.

[Clinical evaluation of intra-arterial infusion chemotherapy for advanced or recurrent cervical cancer with or without radiotherapy].

We analyzed 52 cases of advanced or recurrent cancer of the cervix treated by intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. IAIC regimen was separated into two groups: Group I consisted of 5-FU + MMC +/- ADR (30 cases) and group II of CDDP + MMC +/- 5-FU (22 cases). The tip of the catheter was placed in the bifurcation of abdominal aorta or the bilateral internal iliac arteries (7 cases). The overall response rate (CR + PR) was 71%, 87% in patients given radiotherapy, 50% in those without radiotherapy, and 100% in primary cases. The five-year survival rate was 20% in primary cases, 14% in recurrent cases, 3% in Group I and 38% in Group II (p = 0.00182) by chemotherapy regimen. Severe (more than grade III) hematological acute side effect was 48% for all cases, but recovered by interruption of drugs. In 7 cases in which the tip of the catheter was placed in internal iliac arteries, there were severe skin ulcers in 2 cases and severe pain of leg or gluteal region requiring narcotics in 2 cases. These data suggest that IAIC mainly with cisplatin with or without radiotherapy is one of the effective treatments for advanced or recurrent cervix cancer. But we should check the blood flow distribution periodically, and control the concentration of drugs.

[Clinical evaluation of intra-arterial infusion chemotherapy for advanced or recurrent pelvic tumors with or without radiotherapy].

We analyzed 97 cases of various advanced or recurrent pelvic tumors which were cervix, rectal, ovarian and other tumors treated by intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. The IAIC regimen was separated into two groups: group I consisting of 5-FU + MMC +/- ADR (54 cases) and group II consisting of CDDP + MMC +/- 5-FU (43 cases) from 1985. The catheter was placed in the bifurcation of abdominal aorta, and from 1990, the catheters were placed in bilateral internal iliac arteries (8 cases). The overall response rate (CR + PR) was 65%, 74% in patients receiving radiotherapy, and 47% in those without radiotherapy. There were no significant differences between each primary site and presence of radiotherapy combination in survival rate. Two-year survival rate and 5-year survival rate was 32% and 15% for all cases, and 65% and 33% for CR cases, respectively. A significantly better survival rate was obtained in patients with CR. Five-year survival rate was 4% in group I, and 35% in group II (p = 0.00216) by chemotherapy regimen. Severe (more than grade III) hematological acute side effects were 45% for all cases. In 8 cases in which the catheters were placed in internal iliac arteries, there were severe skin ulcers in 2 cases, and severe pain of leg or gluteal region requiring narcotics in 3 cases. These data suggest that IAIC mainly with cisplatin with or without radiotherapy is one of the effective treatment for advanced or recurrent pelvic tumors. Also, we should check blood flow distribution periodically, and control the concentration of drugs.

[Effectiveness of 3 ways method in intra-arterial infusion chemotherapy for advanced or recurrent cervical cancer with or without radiotherapy].

We analyzed 58 cases of advanced or recurrent cervical cancer treated with intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. Two separate IAIC regimens were administered since 1985: group I consisted of 5-FU + MMC +/- ADR (30 patients) and group II consisted of CDDP + MMC +/- 5-FU (28 patients). The tip of a catheter was placed in the bifurcation of the abdominal aorta (1 way method: 45 patients regimen II: 15) between 1977-1984. We have used selective catheterization (2 ways method: 9) since 1995 in order to get good drug distribution. However we experienced grade 4 toxic effect of cutaneous and pain with this method, so we have used a 3 ways method (4 patients) since 1998. The two-year survival rete was 60% with the 1 way method, and 67% with the 2 ways method and regimen II. Severe adverse effects (grade 3 + 4) were found in 53, 56, 0%, respectively, by each of the three methods (1, 2, 3 ways) hematologically, 13, 22, 0% in gastrointestinally, 0, 44, 0% in cutaneously and 0, 56, 0% in pain or neurotoxicity. These data suggest that IAIC by the 3 ways method is a useful treatment for advanced or recurrent cervical cancer. However, one should check the blood flow distribution periodically, and control concentration of drugs.

[The study of genetic changes in colorectal cancer accompanied with ulcerative colitis].

The usefulness of gene information was studied when used in conjunction with a morphological diagnosis of either dysplasia or carcinoma that later develops into ulcerative colitis (UC). The cases investigated consisted of those operated on for UC with carcinoma complications and those operated on for UC over 7 years previously without carcinoma complications. Ras and DCC were examined for the presence of any point mutations in codon 12 and polymorphism in codon 201 using the PCR-RFLP method, while p53 was also studied immunohistologically. A mutation in ras was found in 25% of the UC-IV cases and also in 17% of the UC-III cases, while no mutation at all was found in the UC-I and UC-II cases. p53 showed a high rate of positivity in the UC-IV and UC-III cases with carcinoma complications, while it was negative in all cases in the control group cases. Gly in DCC codon 201 was also found in many cases including the control group. This study demonstrated that a gene aberration can thus influence the pathophysiology and cancerization of UC and therefore the p53 findings were thus considered to be useful in the morphological diagnosis of dysplasia and carcinoma.

[Portal hemodynamic changes from TIPS--evaluation with pulse Doppler method].

Transjugular intrahepatic portosystemic shunt (TIPS) was applied in three patients with Child C liver cirrhosis. Portal venous pressure was reduced by an average of 10.7 mmHg, and results such as the disappearance of esophageal varices and reduction in ascites were obtained. The portal hemodynamics of these three patients was observed before and after TIPS using the pulse Doppler method. When portal hemodynamics in the main portal vein was examined before TIPS, it was found that the mean blood flow velocity had decreased, the blood flow volume was reduced and the cross-sectional area of the vein had increased. The congestion index was high and there was definite congestion of the portal venous system. After TIPS, the blood flow velocity and volume increased, the cross-sectional area of the vein was reduced and the congestion index was lower. Congestion of the portal venous system was improved in these three patients and the clinical efficacy of TIPS was proven by these results. If the stent can be detected sonographically, stent patency is easily confirmed with the pulse Doppler method which is usefull examination technique for follow-up of patients undergoing TIPS.

[Demonstration of normal bile duct and pancreatic duct with MR cholangiopancreatography].

Demonstration of normal bile duct and pancreatic duct with MR cholangiopancreatography was assessed in 78 patients including 19 cases of not impacted gallstone. Breath hold 2D-MRCP and intermittent breath hold 3D-MRCP was performed with half-Fourier fast spin echo technique using 1.5 T imager and surface coil. Diagnostic depiction rates of main pancreatic duct were 99% in the head, 97% in the body, and 91% in the tail, and of extrahepatic bile duct was 100%. Visualization of accessory pancreatic duct was 42%, but of side branch of pancreatic duct in the body to tail was poor. Anatomic variants of the biliary tree were seen in 15 cases. The reason of poor demonstration was the poor breath hold. In the majority of patients, MRCP can provide the accurate information of pancreaticobiliary tract without dilatation.

A chiral synthesis of four stereoisomers of 1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline, an inducer of Parkinson-like syndrome.

Four stereoisomers of 1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline, an inducer of Parkinson-like syndrome, were synthesized by applying a new method of 1,2,3,4-tetrahydroisoquinoline (TIQ) synthesis utilizing the Pummerer reaction as a key step. The chiral centers at C-1 and C-3 were constructed by two routes starting from alaninol (3) and 1-phenylethylamine (4) as a chiral source. Enantiomerically pure 1,3-dimethyl-TIQs (1R,3S)-(2) [corrected], (1S,3R)-(ent-2) [corrected], (1S,3S)-(1) [corrected], and (1R,3R)-(ent-1) [corrected] were prepared in a stereochemically unambiguous manner from 3 in 11 steps (route I) and from 4 in 6 steps (route II). The conformations of tetrahydroisoquinoline ring in 1-methyl, 3-methyl, and 1,3-dimethyl-TIQs were discussed on the basis of their CD, 1H-NMR spectra, and steric energies.

Synthesis of methoxy-2-quinolones via pummerer-type cyclization of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides.

The thionium ions 10 generated by Pummerer reaction of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides 4 caused not only an electrophilic cyclization reaction producing 2-quinolones 8, but also the formation of the vinyl sulfides 5 and 6 in favor of the latter reaction. On the other hand, the treatment of the vinyl sulfides 5 and 6 with p-toluenesulfonic acid induced cyclization to afford the 2-quinolones 8 in excellent to moderate yields, depending on the electronic properties of the aromatic ring, thus providing a convenient method for the synthesis of methoxy-2-quinolones.

Aporphine glycosides from Stephania cepharantha seeds.

Two new aporphine glycosides, stesakine-9-O-beta-D-glucopyranoside (1) and N-methylasimilobine-2-O-beta-D-glucopyranoside (2), were isolated from the seeds of Stephania cepharantha cultivated in Japan, together with 16 known alkaloids. The structures of 1 and 2 were spectroscopically determined by comparison of their (1)H and (13)C NMR data with those of stesakine (11) and N-methylasimilobine (12), respectively.

Acetylleucine chloromethyl ketone, an inhibitor of acylpeptide hydrolase, induces apoptosis of U937 cells.

Acetylleucine chloromethyl ketone (ALCK), an inhibitor of acylpeptide hydrolase (ACPH), inhibited the growth of human monoblastic U937 cells in a dose- and time-dependent manner. Morphology of the ALCK-exposed cells showed typical apoptosis, judging from the nuclear condensation and segmentation. Chromosomal DNA of U937 cells treated with ALCK showed an internucleosomal ladder-like pattern on electrophoresis, being characteristic of apoptosis. Of the other leucine chloromethyl ketone analogues, butyloylleucine chloromethyl ketone (BLCK) induced a weak ladder-like formation but caploylleucine chloromethyl ketone (CLCK)barely did. On the other hand, intracellular ACPH activity of U937 cells was strongly inhibited by culturing with ALCK, moderately with BLCK, and not with CLCK. These findings indicate that the inhibition of ACPH activity leads to apoptosis and suggest that ACPH may play a vital role in eukaryotic cells.

A synthesis of 3-phenyl-1,2,3,4-tetrahydroisoquinoline and 2-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepine via Pummerer-type cyclization: enhancing effect of boron trifluoride diethyl etherate on the cyclization.

A synthesis of 6,7-dimethoxy-3-phenyl-1,2,3,4-tetrahydroisoquinoline (14a) and 7,8-dimethoxy-2-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepine (14b) was achieved via the cyclization of N-(3,4-dimethoxyphenyl)methyl-1-phenyl-2-(phenylsulfinyl)ethylformamide (6a) and N-2-(3,4-dimethoxyphenyl)ethyl-1-phenyl-2-(phenylsulfinyl)-ethylformamide (6b) using the Pummerer reaction as a key step, respectively. The Pummerer reaction of 6a,b under usual conditions using trifluoroacetic anhydride yielded the vinyl sulfides (8a, b), non-cyclized products, as a major product. The cyclization proceeded when boron trifluoride diethyl etherate was used as an additive reagent, thus giving rise to the corresponding cyclized products (7a) and (7b) in moderate yields. We propose that the enhancing effect of the Lewis acid on the cyclization may be attributable to the involvement of a dicationic intermediate, sulfonium-carbenium dication (23).

Intramolecular capture of pummerer reaction intermediates by an aromatic nucleophile: selective construction of 1,4-benzothiazine and indole ring systems.

The simple alkyl sulfoxide 6 carrying two aromatic nucleophiles, when treated with trifluoroacetic anhydride at room temperature (Pummerer reaction conditions), underwent an intramolecular aromatic sulfenylation of the 6-exo-tet process in an exclusive manner to yield two regioisomeric 1,4-benzothiazine derivatives, 8 and 9. On the other hand, a similar reaction of the alpha-acyl sulfoxide 7, possessing identical aromatic nucleophiles, caused an intramolecular aromatic alkylation of the 5-exo-trig process to produce the 3-oxo-indole derivative 14 in a quantitative yield. These results demonstrate that the construction of 1,4-benzothiazine and indole ring systems can be achieved in a selective manner by proper choice of the sulfoxide side chain.

Effects of single and repeated administration of 1,2,3,4-tetrahydroisoquinoline analogs on the binding of [11C]raclopride to dopamine D2 receptors in the mouse brain.

We investigated the effects of intraperitoneal injection of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogs and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the binding of [11C]raclopride to striatal dopamine D2 receptors in mice. The binding of [11C]raclopride, but not of [11C]N-methylspiperone or [11C]nemonapride with higher affinity, to the receptors was significantly decreased immediately after TIQ injection. Neither a dopamine transporter blocker induced such effect nor TIQ affected the dopamine transporter-radioligand binding. Among the compounds investigated, including parkinsonism-inducing TIQ and (R/S)-1-benzyl-TIQ, parkinsonism-preventing (R)- and (S)-1-methyl-TIQ, and probable N-methylated metabolites of TIQ and 1-methyl-TIQ, TIQ and (S)-1-methyl-TIQ had the strongest effect on the binding of [11C]raclopride, and N-methylated derivatives showed less of an effect than the respective parent compounds. The decrease in the binding of [11C]raclopride continued for 7 hours and was followed by an increase until 10 days after the single and subchronic administration of TIQ. These findings suggest that TIQ analogs profoundly stimulated dopamine release which resulted in the competitive inhibition of the binding of [11C]raclopride to dopamine D2 receptors, but did not induce degeneration of the receptors.

Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism-preventing effect of 1-MeTIQ by in vivo measurement of pre-synaptic dopamine transporters and post-synaptic dopamine D(2) receptors in the mouse striatum.

Parkinsonism-inducing neurotoxicity of 1,2,3,4-tetrahydroisoquinoline (TIQ), as contrasted to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and parkinsonism-preventing effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) have been investigated in mice by measuring their effects on the in vivo binding of radioligand to pre-synaptic dopamine transporters (DATs) or to dopamine D(2) receptors (D2R) in the striatum. A significant reduction of the ligand-DATs binding was found in the mice treated with MPTP, but not with TIQ, under the dosage inducing behavioral abnormality and loss of tyrosine hydroxylase-positive cells in the substantia nigra. A slight decrease in the ligand-DATs binding was observed in the mice given a larger dose of TIQ. Compensatory up-regulation in the post-synaptic D2Rs was found in the MPTP-treated mice. Pre-treatment with (S)-enantiomer, but not (R)-enantiomer, of 1-MeTIQ prevented the degeneration of DATs to some extent. We concluded that the TIQ-induced parkinsonism model is different from the MPTP-induced model as evaluated by the radioligand-DATs binding and that (S)-1-MeTIQ has a preventing effect for the degeneration of the DATs to a certain extent.

Balloon-occluded retrograde transvenous obliteration (BRTO), a promising nonsurgical therapy for ectopic varices: a case report of successful treatment of duodenal varices by BRTO.

We present a patient with massive tarry stool, diagnosed as duodenal varices bleeding. Endoscopic ligation (EL) therapy was carried out for the varices, but because the possibility of re-bleeding remained, we treated the varices with balloon-occluded retrograde transvenous obliteration (BRTO), and duodenal varices were successfully decompressed without any complications. BRTO might be a novel therapeutic approach for ectopic varices, including duodenal varices.

A novel therapeutic approach for rectal varices: a case report of rectal varices treated with double balloon-occluded embolotherapy.

We present a patient with continuous melena, diagnosed as rectal varices bleeding. She had a history of esophageal varices, which was treated by endoscopic ligation therapy. Eight years after the treatment of esophageal varices, the continuous melena began. Colonoscopic examination showed that the melena was caused by rectal varices, which were so severe that they could not be treated by either endoscopic sclerotherapy or surgical devascularization. Taking into considering the overall risk of treating rectal varices, we chose the approach of double balloon-occluded embolotherapy (DBOE) with 5% ethanolamine oleate with iopamodol as a liquid embolic material. DBOE is one of the interventional radiology techniques (Morita et al., Acta Hepatol Jpn 1994;35:109-120), but in this case was a completely new and novel clinical procedure for rectal varices. After the DBOE therapy, the condition of rectal varices was markedly improved. Thus, DBOE might be a new tool for treating inoperable rectal varices.