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An asymptomatic 78-year-old woman with anemia had undergone abdominal ultrasonography 6 years ago, which revealed a 7-cm hepatic tumor. The patient was regularly followed-up assuming that the tumor was a hepatic hemangioma with cyst. However, the tumor gradually increased in size. Abdominal CT and MRI revealed that the tumor comprised a mixture of cystic and solid components, and there was dilation of the bile duct. A clinical diagnosis of intraductal papillary neoplasm of the bile duct was made. Caudate and right hepatic lobectomy was performed. The pathological diagnosis of the tumor was a papillary adenocarcinoma. This case, in which the patient was followed for 6 years before curative surgical treatment, is significant, because it demonstrates the slow-growing nature of this tumor.

Joubert syndrome is characterized by neonatal breathing disorders that are thought to improve with age, but recent findings indicate that sleep-related breathing disorders can occur even after infancy. A 15-year-old boy who had a breathing disorder during the neonatal period developed mental retardation and hypotonia. He was diagnosed with Joubert syndrome based on the clinical course and molar tooth sign on brain MRI at 9 years of age. Daytime sleepiness developed at 15 years of age. An interview and the results of sleep questionnaires (Epworth sleepiness scale, Pediatric sleep questionnaire and Pittsburgh sleep quality index), indicated that the patient had daytime sleepiness and a sleep-related breathing disorder. Overnight polysomnography showed central apnea with an apnea hypopnea index of 16, indicating that the patient had central sleep apnea syndrome. After nighttime oxygen therapy at home for one month, the sleep questionnaires showed improved daytime sleepiness and the sleep-related breathing disorder. The improvement persisted for over 12 months thereafter. Sleep-related breathing disorders could be indicated by non-specific complaints such as daytime sleepiness and lead to appropriate therapies. Such disorders should be considered as a complication of Joubert syndrome even after infancy.

Objective: We have frequently applied noninvasive positive pressure ventilation (NPPV) to treat acute respiratory failure in children with severe motor and intellectual disabilities. We investigated the features and causes of conditions requiring endotracheal intubation. We aimed to determine whether phlegm expulsion using appropriate breathing physiotherapy with NPPV could avoid the need for endotracheal intubation in such patients. Methods: Between December 2010 and November 2012, 21 children with 51 episodes of acute respiratory failure were placed on NPPV at our hospital. We investigated the ratio, background, and causes of conditions requiring endotracheal intubation. Results: Pneumonia and bronchitis caused 30 and 21 episodes of respiratory failure, respectively. Respiratory infection required endotracheal intubation in 8 of 30 episodes of pneumonia, and in none of the 21 episodes of bronchitis. Respiratory infections were caused by upper airway obstruction with large amounts of secretion (n=4), lower airway obstruction due to atelectasis (n=3) and a combination of both (n=1). The frequency of breathing physiotherapy was significantly higher for all patients who required assistance with active phlegm expulsion than in those who did not (p=0.006). More patients on endotracheal intubation also required phlegm aspiration compared with other patients (p=0.019). Conclusion: We applied NPPV to acute respiratory failure in children with severe motor and intellectual disabilities. This allowed 84% of them to avoid endotracheal intubation. Acute respiratory failure did not improve in any patient who required endotracheal intubation, but we also used NPPV with breathing physiotherapy and postural drainage. Assistance with phlegm expulsion is hampered in children with severe motor and intellectual disabilities due to conditions such as thoracic deformations, joint contracture and glossoptosis. We consider that assistance with phlegm expulsion using appropriate breathing physiotherapy with NPPV is very important for such patients.

The abdominal complications of Duchenne muscular dystrophy (DMD) include acute gastric dilatation, superior mesenteric artery (SMA) syndrome, ileus and constipation. We report herein a patient with DMD in whom SMA syndrome was successfully treated with enteral tube nutrition. The patient was a 16-year-old boy diagnosed with DMD at 2 years. Steroid therapy was started at 5 years, and he was unable to walk and was wheelchair-bound at 11 years. Lordoscoliosis progressed after the age of 14 years. Noninvasive mechanical ventilation was introduced due to respiratory impairment at 15 years. During 8 months with respiratory impairment, his body weight decreased from 40.3 kg to 33.4 kg. He was referred to our hospital for vomiting and hematemesis. Radiographic studies indicated a diagnosis of SMA syndrome. Enteral nutrition with a nasojejunal tube successfully treated SMA syndrome for 5 months and his body weight increased from 32.7 kg to 36.1 kg. Gastrostomy was subsequently performed and no recurrence was evident. SMA syndrome is caused by compression of the third part of the duodenum at the angle between the aorta and SMA. The conditions for duodenal vascular compression are weight loss resulting in depletion of the retroperitoneal fat and progressive lordosis. The reasons for SMA syndrome with our patient were weight loss and progressive lordoscoliosis. A conservative approach with enteral nutrition promoted weight gain, increasing retroperitoneal fat. Enteral nutrition should be considered for the treatment of SMA syndrome as a complication of DMD.

Background and Methods: We have noticed the possibility that preoperative spirometry may discover latent COPD patients. When COPD is discovered before operation, we can start to treat COPD promptly. Consequently, the better perioperative care is given to COPD patients. On discharge, patients are referred to their family doctors, so that they can receive COPD treatment., Results: There activities were started in July 2012. During the initial twelve months, 90 patients of COPD II x III were discovered and treated before admission. FEV1.0 was significantly improved (1.54 l vs. 1.71 l in average) on repeated spirometry on admission. There was no adverse event in COPD treatment All patients have shown good clinical courses., Conclusions: Latent COPD patients can be discovered by preoperative spirometry.

Creatine transporter deficiency (CRTR-D) is an X-linked disorder characterized by hypotonia, developmental delay, and seizures. We report the third Japanese family with CRTR-D. The proband was an 8-year-old boy who presented with hypotonia, severe intellectual disability and two episodes of seizures associated with/without fever. Among 7 siblings (4 males, 3 females), the eldest brother had severe intellectual disability, epilepsy, and sudden death at 17 years of age, while 18-year-old third elder brother had severe intellectual disability, autism, and drug-resistant epilepsy. The proband's urinary creatine/creatinine ratio was increased. A reduced creatine peak on brain magnetic resonance spectroscopy and a known pathogenic mutation in the SLC6A8 gene (c.1661 C > T;p.Pro554Leu) confirmed the diagnosis of CRTR-D. The same mutation was found in the third elder brother. Their mother was a heterozygote. Symptoms of CRTR-D are non-specific. Urinary creatine/creatinine ratio should be measured in patients with hypotonia, developmental delay, seizure and autism whose family history indicates an X-linked inheritance.

Objective: Severe muscle hypertonia in patients with the mixed type of tetraplegia may be associated with significant deterioration in the quality of life of the patients. Intermittent use of oral muscle relaxant drugs, for example, Tizanidine (Ternelin), which is a fast-acting muscle relaxant, can provide relief from the severe hypertonia in these patients, but only for short durations., Methods: We conducted a retrospective study of the effect of continuous infusion of tizanidine via a feeding tube on the severe systemic muscle hypertonia in patients with the mixed type of tetraplegia. We mixed tizanidine with milk or other enteral nutrients and administered the mixture via a naso-duodenal tube at a constant infusion rate several hours to 5 patients with the mixed type of tetraplegia showing severe uncontrolled systemic hypertonia under intermittent treatment with oral muscle relaxant drugs., Results: Significant relief from the systemic muscle hypertonia was obtained in 4 of the 5 patients with improvement of the quality of life of the patients, e. g., they could get adequate sleep. There were no serious side effects in any of the cases., Conclusion: We consider that continuous infusion of tizanidine via a feeding tube would be useful for the treatment of severe systemic hypertonia in patients in whom the symptom cannot be adequately controlled by intermittent use of oral muscle relaxant drugs.

Purpose: Both to evaluate the characteristics of food allergic children who were prescribed an adrenaline autoinjector and to assess whether it was used appropriately., Methods: The characteristics of food allergic children who were prescribed an adrenaline autoinjector were investigated. Among these children, those who experienced severe anaphylaxis due to inadvertent ingestion were analyzed, as was whether and how the autoinjector was used., Results: An adrenaline autoinjector was prescribed to 139 food allergic children, most often for egg, followed by milk and wheat allergies. Concomitant bronchial asthma, atopic dermatitis, and food allergies of other causes were present in 49 (35.3%), 68 (48.9%), and 102 cases (73.4%), respectively. The most frequent organ involved in anaphylaxis was the skin (94.2%), followed by the respiratory (78.5%), digestive (28.1%), and circulatory (24.8%) organs. A total of 24 cases experienced severe anaphylaxis after the prescription; however, the autoinjector was used in only six (25%) of those cases. The reasons given for lack of use included fear of use, unavailability of the autoinjector, prior improvement with use of an oral antihistamine and immediate visit to a hospital emergency department in eight, five, three and one case, respectively., Conclusion: These results suggest that the autoinjector is often not used appropriately after prescription. Therefore, children and their caregivers require more effective guidance on proper adrenaline autoinjector use.

A 37-year-old Japanese man undergoing treatment for dilated cardiomyopathy was presented with weakness and melena. He had conjunctival pallor and difficulty in standing;his blood pressure was 81/62 mmHg. Abdominal computed tomography revealed contrast dye leakage into the small intestine. He was diagnosed with hemorrhagic shock secondary to intestinal bleeding;we administered large volumes of intravenous fluid along with performing a blood transfusion. We then performed angiography to determine the site of bleeding angioectasia and placed a catheter into the affected artery. We identified the resection site using an intraoperative dye infusion via the catheter, and successfully performed small bowel resection. He was subsequently discharged without complications.

Objective: Ketogenic diets tend to cause trace mineral deficiencies. Ketonformula is a foumula for a ketogenic diet developed by Meiji Co Ltd in Japan. No reports are available on the trace mineral deficiencies associated with a use of Ketonformula., Methods: We monitored the serum levels of selenium, zinc and copper as well as the amount of the daily intake of these minerals before and at 6 months after the initiation of the ketogenic diet with Ketonformula in six patients with intractable epilepsy associated with severe motor and intellectual disabilities., Result: The median serum selenium concentration decreased from 7.0 (range, 6.5-12.3) microg/dl to 6.2 (5.4-10.9) microg/dl as a result of the 6-month-treatment with Ketonformula (p < 0.05, Wilcoxon signed-rank test). The median daily selenium intake decreased from 17.8 (15.0-27.0) microg/day at the baseline to 5.5 (5.0-22.0) microg/day after 6 months on the diet (p < 0.05). The median serum zinc concentration increased slightly (from 66.0 (46.0-84.0) microg/dl to 68.0 (46.0-71.0) microg/dl), but the difference was not significant. The median daily zinc intake, however, significantly decreased from 4.2 (3.7-6.0) mg/day to 2.2 (2.0-3.0) mg/day (p < 0.05). The median serum copper concentration also showed no significant decrease (from 134.5 (119.0-168.0) microg/dl to 126.0 (86.0-183.0) microg/dl). The median daily copper intakes, however, decreased significantly from 0.80 (0.35-1.30) mg/day to 0.30 (0.26-0.40) mg/day (p < 0.05)., Conclusions: The decline of the serum selenium concentrations and daily enteral intakes of selenium, zinc, and copper after 6 months on Ketonformula suggested that patients on this ketogenic formula needs close monitoring as well as supplementation of these trace minerals.

Objective: We investigated the efficacy, safety, and tolerability of high-dose topiramate with rapid dose titration in 12 children with symptomatic West syndrome who suffered from severe motor and intellectual disabilities., Methods: Topiramate was introduced as add-on therapy at the daily dose of 1 mg/kg/day, followed by increments of 2 mg/kg at 3- or 4-day intervals, up to a maximum of 19 or 20 mg/kg/day. The ages at the start of topiramate therapy ranged from 5 to 22 months. Prior to the topiramate therapy, the patients had received 2 to 6 antiepileptic agents with (8 patients) or without ACTH (4 patients)., Results: Topiramate appeared to be effective in 8 of the 12 patients (67%); four became seizure-free;three showed greater than 90% seizure reduction; one showed greater than 50% seizure reduction. The maintenance dose was 7 to 20 mg/kg/day (mean:17.9 +/- 3.9 mg/kg/day). In 4 of these 8 patients (50%), the spasms relapsed several months after complete cessation or diminution in the frequency of the spasms following treatment with topiramate. All of the 8 topiramate-responsive patients could continue the topiramate therapy throughout this study. The duration of topiramate therapy was 7 to 42 months (median: 12.5 months). There were no severe side effects that necessitated discontinuation of topiramate, including kidney stones., Conclusions: High-dose topiramate with rapid dose titration was revealed to be effective, safe, and well-tolerated in children with symptomatic West syndrome.

The ketogenic diet (KD) is a high-fat, low-protein, low-carbohydrate diet which is effective in the treatment of medically refractory epilepsy. Several theories have been proposed to explain the mechanism underlying the anticonvulsant efficacy of the KD, however, the precise anticonvulsant mechanism of the KD is still unknown. We speculated the mechanism underlying the effect of the KD in patients with intractable epilepsy, based on the results of the [11C] flumazenil (FMZ)-positron emission tomography (PET) study. A patient developed frontal lobe epilepsy at the age of 2 years. At the age of 4 years 11 months, she was admitted to our hospital for the initiation of a KD. At the time of admission, she had several epileptic attacks each day: frequent postural tonic seizures, hypermotor seizures, head nodding, and intermittent loss of consciousness (non-convulsive status epilepticus). MR imaging showed no abnormal signal intensity in the brain. With the KD, the seizure frequency reduced dramatically on the fifth day. Interictal [11C] FMZ-PET was performed before and 2 months after the initiation of the KD. Before the KD, the [11C] FMZ-PET images and [11C] FMZ-PET binding potential (BP) images showed extremely low accumulation of FMZ throughout the cerebral cortex. Two months after the initiation of the KD, significantly increased binding potential of [11C] FMZ was observed, implying the increased binding potential of the benzodiazepine receptors, probably due to the anticonvulsant effect of the KD. These PET findings suggested that KD may control seizures by directly or indirectly increasing the binding potential of the benzodiazepine receptors.

Three experiments were conducted to investigate the effects of feature similarity and discrimination category in a flanker task. Gabor patches were used as target and distractor stimuli for each experiment. In the first experiment, the target turned to minus or plus 45 deg from the vertical, whereas the orientation of the distractors changed between minus and plus 45 deg by 15 deg. For the second experiment, three conditions of the target orientation were used: minus or plus 45 deg, minus 22.5 deg or plus 67.5 deg, and 0 deg or plus 90 deg. The orientation of the distractors changed between the orientations of the two targets by 22.5 deg. In the third experiment, the target turned to minus or plus 10 deg from the vertical, whereas the orientation of the distractors changed between minus and plus 40 deg by 5 deg. The results showed that responses to the target were affected by the difference between the orientations of the target and the distractors as well as the category of their orientations.

We describe a 72-year-old man admitted to hospital as an emergency case of epigastric abdominal pain. CT scan visualized massive hemorrhage around the pancreatic head. Computed tomographic angiography showed stenosis at the origin of the celiac artery and a 10 mm aneurysm of the posterior inferior pancreaticoduodenal artery (PIPDA). An emergency angiogram revealed a long aneurysm in the PIPDA. The aneurysm had irregular width and was 75 mm in length. A gastroduodenal artery and the PIPDA were supplied from the superior mesenteric artery. A transcatheter arterial embolization (TAE) was performed. We reviewed 45 cases of pancreaticoduodenal aneurysms after 2000 and cases of the pancreaticoduodenal false aneurysms after 1972. As a result, we inferred that this case without pancreatitis or pancreas surgery was a true aneurysm made by the bloodstream changes caused by the celiac artery stenosis.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder and is the most common form of muscular dystrophy. Affected children develop muscle weakness in early childhood. Only steroids have been shown with evidence to improve muscle function in patients with DMD. We report the long-term effects of prednisolone treatment in patients with DMD, comparing the age at which 14 treated patients and 15 control patients lost their ability to walk. The prednisolone-treated patients were assigned to one of five regimens: 0.5 mg/kg/day given for the first 10 days of every month (n = 6), 0.75 mg/kg/day given for the first 10 days of every month (n = 3), 0.5 mg/kg on alternate days (n = 1), 0.75 mg/kg on alternate days (n = 1), or 5 mg/kg twice a week (n = 3). No significant difference in age of losing ambulation ability was observed between the treated group and the untreated group (mean age; 10 years and 6 months in both groups). However, 13 of the 14 patients showed an improvement in their activity of daily living other than ambulation in the treated group. The results of this study showed that the prednisolone treatment regimens used in this study did not prolong the period of ambulation.

We examined the antiepileptic effect and side effects of sulthiame in 28 patients with intractable epilepsy. The patients' ages ranged from 6 months to 34 years (mean: 8 years 7 months), and 26 of them were under 18-years-old. Nineteen patients had severe physical and mental disabilities. Sixteen patients had generalized seizures, and 12 had partial seizures. Sulthiame was administered at the dose of 50-300 mg/day (4-14 mg/kg body weight) as add-on therapy in all except one patient. Among the 28 patients, two with complex partial seizures (7%) became seizure-free. Eight patients (29%) (6 patients with generalized seizures and 2 patients with partial seizures) showed seizure reduction by > 50%. Among these 10 patients who showed positive responses, six developed tolerance within 2-5 months. Side-effects were observed in 5 patients, including enuresis, drowsiness, and drooling, none of which caused discontinuation of treatment. Therefore, we conclude that sulthiame is an effective and safe antiepileptic drug for the treatment of intractable epilepsy.

In visual search situations, it is known that not only bottom-up factors relative to the presented stimulus display but also top-down factors, which include foreknowledge about the target or observers' strategies for the task, have an influence on search performance. The present study examines how top-down attentional control settings affect the visual search process by using the within-dimension facilitation (WDF) and the inter-trial facilitation (ITF) effects. In Experiment 1 we showed the WDF effect using foreknowledge about the target-defining dimension within one block. In Experiment 2 we found the ITF effect using foreknowledge about the target-defining dimension in every trial. These results suggest that search performance is improved both top-down attentional setting using foreknowledge and inter-trial priming by repetition of target-defining dimensions, and they are interactive. Furthermore, the influence of the priming effect strongly appeared when observers had an attentional setting every trial. These results show that the magnitude of bottom-up inter-trial priming effects depends on the top-down attentional setting.

We report here a boy with epilepsy and congenital heart defect, complicated postoperatively by complete atrioventricular (A-V) block caused by an adverse effect of carbamazepine (CBZ). He had been taking CBZ for 7 years to treat complex partial seizures. He also had endocardial cushion defect and first-degree A-V block, and underwent cardiac surgery at the age of 17 years. The postoperative course was unremarkable except transient complete left bundle branch block occuring one day after the surgery. Oral CBZ (400 mg per day) was continued. Five days after the surgery, bradycardia (20 beats per minute) suddenly developed, and electrocardiography (ECG) showed complete A-V block. Pervenous pacing was begun, and the heart rate gradually recovered. CBZ was discontinued on the suspicion that it caused the arrhythmia, although its serum level was estimated to be within the therapeutic range (4 to 5 microg/ml). He underwent pervenous pacing for 12 days. He was discharged 27 days after the surgery, when ECG returned to first-degree A-V block. In this case, the cardiac conduction system was affected by an adverse effect of CBZ, in combination with the preoperative first-degree A-V block and the effects of cardiac surgery, resulting in complete A-V block. Although reports of similar cases are scarce, caution should be made in prescribing CBZ to patients who either have cardiac conduction abnormalities or undergo cardiac surgery.

Serum amylase is most commonly used as a biochemical marker of acute pancreatitis (AP). But it lacks specificity. The serum lipase level is more accurate and a better marker. Serum elastase -1 level is specific and remains elevated longer, but its radioimmunoassay is not routinely used. Recently, it can be rapidly measured by latex turbidometric immunoassay with automatic analyzer. Biochemically, only CRP test is available and useful to assess severity, but its sensitivity is unacceptably low in the early course of the disease. Urinary trypsinogen activation peptide (TAP) or trypsinogen-2 is an earlier marker. Increasing knowledge of the inflammatory process in AP has led to possibly useful biochemical indicators of severity, such as cytokines, nonpancreatic synovial type group II PLA2 or granulocyte elastase.

Hepatic metastases are a frequent complication of colorectal cancer. Resection of liver metastases can result in long-term survival. However, the majority of patients have unresectable disease. Alternative methods in Japan for treating these patients are hepatic arterial infusion (HAI) chemotherapy with administration of 1,000 mg/m2 of 5-FU over 5 hours. We summarize the status of HAI chemotherapy in terms of colorectal hepatic metastases today. HAI chemotherapy produced higher response rates compared with systemic chemotherapy, but did not demonstrate elongation of survival time in many trials. Important problems remaining to be solved are the technical aspects of percutaneous implantation of intraarterial catheters connected to a subcutaneous infusion reservoir and studies of combined therapy with systemic chemotherapy. Furthermore, in order to finally determine the position of HAI for colorectal liver metastases, it is necessary to conduct a comparative study versus systemic chemotherapy, using the survival time as the primary end point.

We report here an infant with 18q deletion syndrome, and intractable apneic seizures. He had intrauterine growth retardation and dysmorphic features. Chromosomal analysis demonstrated mosaicism of 18q interstitial deletion (q12.3-q22.3). From the age of 3 months, apneic attacks occurred from once a week to over 10 times a day despite many oral antiepileptic agents, and were diagnosed as complex partial seizures. Ictal electroencephalogram and 18F-fluorodeoxyglucose-positron emission tomography at the age of 10 months identified the epileptic focus in the right parieto-temporal region. He also had severe psychomotor retardation. Head MRI examination revealed diffuse cerebral atrophy and severe white matter dysmyelination, which was caused by the deletion of myelin basic protein gene at the locus of 18q22.3. This locus may be responsible for the clinical manifestations of 18q deletion syndrome. Detailed description of the onset, seizure types, and prognosis of epilepsy associated with 18q deletion syndrome is rare. It was suggested that the locus of 18q21.3-q22.3 was responsible for autonomic seizures in 18q deletion syndrome.

An 11-year-old boy gradually developed headache, vomiting and diplopia over a period of 1 month. Repeated examinations of head CT scan revealed an arachnoid cyst in the right middle cranial fossa and bilateral subdural effusion of enlarging size. Papilledema was absent on admission, but it became evident after 1 week, and lumbar puncture disclosed very high pressure (800 mmH2O) of the cerebrospinal fluid. Fenestration of the cyst to the basal cisterms quickly alleviated his symptoms of intracranial hypertension as well as the bilateral subdural effusion on CT. Macroscopically, there was a small tear on the wall of the arachnoid cyst, and it probably served as a communication valve with the subdural space. Since he had no history of head trauma in the past few months, the reason of the tear formation was unclear. Intracranial arachnoid cyst is a relatively common congenital malformation of usually benign and non-pathogenic nature. However, it may occasionally cause non-traumatic subdural effusion and intracranial hypertension.

In Japan, interventional radiology (IVR) treatments such as transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), and intraarterial infusion chemotherapy play an important role in the treatment of hepatocellular carcinoma because of the associated cirrhosis (impairment of liver function) and occasional multicentricity. With progress in catheters, embolic materials, and imaging equipment such as the so-called "IVR-CT", superselective TAE and precise evaluation of tumor lesions has become feasible. However, the impact of TAE on survival in patients with hepatocellular carcinoma remains to be determined because no survival benefit was seen in four of five randomized controlled trials (RCTs) in Europe and Eastern countries, in which TAE was compared with no treatment (3 trials), i.v. 5-fluorouracil (1 trial), or tamoxifen (1 trial). To resolve questions arising from these results, a fair number of trials, particularly RCTs are needed in Japan.

Recently, degradable starch microspheres (DSM) have become available for use in patients with liver cancer in Japan. When DSM combined with a cytotoxic drug are infused through the hepatic artery, the steep drug concentration gradient to the tumor tissue results in a higher tissue drug concentration, which may elicit an increased antitumor response by blocking regional blood flow. Furthermore, the reduced systemic exposure of a coinjected drug can be translated into an increased regional extraction ratio due to blood flow reduction. DSM is infused via a catheter connecting to a subcutaneously implanted reservoir in outpatients. Pain is experienced by all patients. Other frequently observed adverse reactions are nausea and vomiting. However, these symptoms improve within a few hours. These observations indicate that intra-arterial chemotherapy combined with DSM may provide a more potent anticancer effect than a cytotoxic drug alone.

We had the opportunity to use "Vital Port", a subcutaneous implantable vascular access port which was developed in the U.S. and has been used clinically in a multicenter study for clinical evaluation. To prevent the result from varying by facility, standardized criteria were made. The access port was implanted in 31 patients, and then intra-arterial infusion chemotherapy was performed. The follow-up period was 4 weeks. No complications were observed in any of the cases. Intra-arterial infusion chemotherapy was carried out without any problem. This port is lightweight and has good biocompatibility, and the clinical results were evaluated highly.

A novel DNA virus, TT virus(TTV), has been reported in patients with posttransfusion hepatitis of unknown etiology. However association between TTV and acute hepatitis has not been shown. We investigated the prevalence of TTV in acute hepatitis. TTV-positive rates in acute hepatitis A, B, C, cytomegalovirus infection, Epstein-Barr virus infection, and acute hepatitis of unknown etiology were 15.3%, 21.8%, 60.0%, 0%, 10.0%, 22.6%, respectively. There were no significant differences in TTV prevalence between each etiology and healthy blood donors(20.8%). Clinical data were similar between patients with or without TTV. In this study we could not find any difference in the prevalence of TTV between acute hepatitis with known etiologies and that with unknown etiology. TTV did not affect the clinical features of acute hepatitis with known etiologies.

We evaluated the usefulness of percutaneous ethanol injection therapy (PEIT) under Carbon dioxide (CO2) contrast enhanced ultrasound sonography (CEUS) guidance during digital subtraction angiography (DSA) in 21 cases of hepatocellular carcinoma (HCC) with 28 nodules that could not be detected by plain (non-contrast enhanced) US (PUS). In all cases of HCC that could not be visualized by PUS, PEIT could be performed successfully under CEUS guidance. Tumor size was below 10 mm in most cases, in 2 cases tumor size was more than 20 mm. Tumor location was roughly divided into 5 areas: just below the diaphragm and it's vicinity, liver surface, edge of the liver, around the portal and hepatic vein, and around the inferior vena cave. The detection rate of the nodules that could not be visualized with PUS was 35.7% for CT and 32.1% for DSA. PEIT was performed 1-9 times for each lesion, 3.32 times on an average. The effectiveness of PEIT was judged by CT. All cases were confirmed as LDA. We concluded that the range of indication of PEIT can be expanded by this method.

Between 1986 and 1994, 66 patients with unresectable liver metastases from colorectal cancer were treated by repeated hepatic arterial infusion chemotherapy employing an implantable port system. In this study, 44 patients who received intermittent hepatic arterial infusion of high dose 5-FU (1000mg/m2) were analysed according to a response rate, survival rates, developments of extrahepatic lesions, periods of hepatic arterial infusion, and the rates at home. Two cases (4.5%) achieved a complete response (CR) and 27 cases (61.4%) a partial response (PR). The overall one-year and two-year survival rates were 56.7% and 37.8% respectively. The 50% survival time for all patients was 17.2 months. During the course of observation, extrahepatic lesions developed in 16 of the 39 patients (41.0%) and many responders died due to deterioration of extrahepatic lesions. The over all rates at home were more than 85%. Hepatic arterial infusion of the 5-FU at 1000mg/m2 every week showed a high response rate in colorectal cancer patients with hepatic metastases, and the responders showed a low rate of death due to the hepatic metastases. However, in many patients the prognosis-determining-factor was extrahepatic lesions. Thus, countermeasures were necessary for extrahepatic lesions.

A 57-year-old man was admitted with aching pain in his left frank. Left renal infarction was revealed by CT scan and arteriogram. Intra-arterial thrombolytic therapy was performed, and resulted in a recanalization of the occluded artery and elimination of frank pain, but residual stenosis was recognized. At 27 hours after the onset of left renal infarction, in spite of the systemic anti-coagulant and thrombolytic therapy to prevent the recurrence of the thrombosis, right renal infarction occurred. Immediate intra-arterial thrombolytic therapy for right renal infarction was performed successfully. Subsequently the serum creatinine level increased from 0.8-0.9 to 1.2-1.3 mg/dl due to the functional loss of the left kidney, which was confirmed by follow-up renoscintigraphy. Conservative intra-arterial thrombolytic therapy seems to be the most effective treatment for renal infarction, but left renal salvage failed due to the prolonged time of occlusion and residual stenosis. Also, catheterization for diagnosis and therapy or thrombolytic therapy itself may induce an additional infarction.

Glycyrrhizin had been used widely for the patients with chronic liver disease. We examined the pharmacokinetics of the glycyrrhizin and glycyrrhetic acid in the blood stream after intra-venous administration of glycyrrhizin. The stream concentration of glycyrrhizin in the patients of liver cirrhosis tend to be kept higher than that of chronic hepatitis but there were no significant difference between them except for after a half hour from the administration. There was negative correlation between ICG R15 and the speed of excretion of glycyrrhizin from the serum. On the other hand, the concentration of the glycyrrhetic acid was kept higher in the patients with liver cirrhosis than that of chronic hepatitis, but there were no significant difference between them except for after a half hour from the administration. These findings suggested that the accumulation of glycyrrhizin and glycyrrhetic acid in the patients of liver cirrhosis can be seen by long term administration.

A total of 96 patients with small hepatocellular carcinoma (HCC) with a maximal diameter of below 2 cm were analyzed according to recurrent factors and recurrent modes after the first treatment. In this study, recurrences were divided into two groups based on the style of recurrences provisionally: intrahepatic metastases (IM, 35 cases) and multicentric recurrences (MC, 22 cases). In patients with IM, the majority of recurrences were observed within 2 years after the first treatment and the primary HCC lesions had strong relation to the degrees of malignancy. On the other hands, there were no association with recurrent intervals and the degrees of malignancy, although the recurrent rate was high in patients with anti-HCV in MC group. The prognosis after the second treatment in MC group was superior to that in IM group (p < 0.05). These results indicate MC group have a good prognosis if early detection and the second accurate treatment are performed.

An anti-allergic drug, permirolast potassium (TBX), inhibited antigen (Ag)-induced phospholipase D (PLD) activation in rat basophilic leukemia (RBL-2H3) cells. The concentration-dependent inhibitory profile for Ag-induced PLD activation was parallel to those for secretory response and inositol phosphate formation. In contrast, TBX had no effect on PLD activation caused by calcium ionophore A23187 or phorbol myristate acetate. These results suggest that TBX inhibits Ag-induced PLD activation by interfering with the signal transduction pathway upstream of Ca2+ mobilization and protein kinase C activation.

We attempted to instruct the outpatients with malignant liver tumor (metastatic liver cancer and advanced hepatocellular carcinoma) who received intermittent arterial infusion chemotherapy using implanted reservoir to detach the devices for arterial infusion by themselves at home. All patients who received our instruction could master self-detachment at home, which shortened the hospitalized day. And patients' desire for this treatment promoted with improvement of the recognition of their families to participate in treatment together. We experienced no trouble which disturb the treatment. This methods was considered to promote the improvement of QOL of these patients.

Between 1986 and 1994, hepatic local arterial infusion chemotherapy with implanted reservoir was performed for 51 patients with hepatocellular carcinoma (HCC) who were not indicated for surgery, PEIT and/or TAE because of the advanced stage of tumors and impaired liver function. We compared direct effects, survival rates, and rates of outpatients by dividing these 51 patients into 3 groups according to the methods of administration--repeated one-shot arterial infusion group, continuous arterial infusion group and intermittent high-dose arterial infusion group. There were no significant differences among these three groups in terms of background factors. The continuous infusion group had significantly better survival rates than the repeated one-shot infusion group, and the survival rate of the intermittent high-dose infusion group was similar to that of the continuous infusion group, although there were no significant differences in effectiveness among the three groups. Patients in the continuous infusion group and intermittent high-dose infusion group could receive almost all of their treatment as outpatients. Furthermore, more patients in the intermittent high-dose infusion group could receive whole treatment without hospitalization than patients in the continuous infusion group. Because intermittent high-dose arterial infusion of 5-FU showed about the same survival rate as continuous arterial infusion and because it can maintain high quality of life, it is suggested to be a standard method for local arterial infusion of 5-FU for severe advanced HCC.

From August 1990 to May 1993, we treated 23 non-complete responders on initial treatment with interferon and studied the factor which affects the effectiveness in the attempt to verify the factors for the selection of patients who are to receive it. Complete response was achieved in 8 (34.8%) patients, while the other 15 patients did not achieve this degree of response. Three patients were of genotype II and 5 of genotype III in these 8 complete responders. All complete responders were patients with relapse who had had normalized serum ALT levels during the initial administration and undetectable HCV-RNA at the end of the period. No patient who failed to achieve normalization of the serum ALT level on initial treatment achieved a complete response on retreatment. HCV-RNA concentration before retreatment was significantly less than the one before initial treatment in 8 complete responders. Interferon retreatment of patients who do not achieve a complete response may be effective in relapsed cases with undetectable HCV-RNA at the end of initial treatment. Selection of patients to receive interferon retreatment requires careful review and consideration of genotype, HCV-RNA concentration, and the clinical response at initial treatment.

We attempted continuous local arterial-infusion chemotherapy using reservoir for patients with severely advanced hepatocellular carcinoma (HCC), with no indications for operation, PEIT or TAE because of the advanced clinical stage, Vp-factor, and so on. Twenty-two HCC patients were given continuous arterial-infusion of 5-FU + CDDP and were observed for 36-443 days from June, 1991 to December, 1992. Until the end of 1992, we had 3 partial response (PR) cases and 3 progressive disease (PD) cases, and the other cases showed no change (NC). Except for a case in which therapy was stopped because of renal failure, no patients were disturbed by side effects, and 68.2% of the patients completed all of their therapy as outpatients. Because CDDP can amplify the effect of 5-FU in addition to its own effect as a biochemical modulator, and because continuous infusion can strengthen the effect of 5-FU and reduce the side effects of CDDP, we consider continuous local arterial-infusion of 5-FU and CDDP to be an effective therapy for severely advanced HCC. This treatment does not cure the carcinoma but helps to slow its progress and assure good QOL.

We tried continuous local arterial-infusion chemotherapy using 5-FU + CDDP with an implanted reservoir, for patients with severely advanced hepatocellular carcinoma (HCC), who had no indications for operation, PEIT or TAE. Arterial-infusion was continued for one week, followed by a one-week no-infusion period, and this treatment was repeated 1-32 times, and patients were observed for 36-549 days. Until the end of April 1993, the one-year survival rate was 61.1%. There were 3 partial remission (PR) cases, 3 progressive disease (PD) cases and the other cases showed no change (NC). Only one patient had any side effects, and all could continue as outpatients for 94.0% of the entire therapy. The patients' evaluation of QOL revealed no differences of QOL according to the length of the whole therapy, the history of rehospitalization during therapy, response to therapy, etc. But PR cases tended to show improved QOL. Therefore we considered this as effective therapy for the elongation of the life-span and the improvement of QOL.

Congestive heart failure (CHF) due to idiopathic cardiomyopathy is reviewed. CHF in dilated cardiomyopathy (DCM) is caused mainly by myocardial systolic dysfunction. Diuretics, angiotensin-converting enzyme (ACE) inhibitors and digitalis are the first choice drugs. ACE inhibitors have been shown to be effective in prolonging life and improving quality of life. Recently, long-term beta-blockade therapy has been shown to be useful. CHF in hypertrophic cardiomyopathy (HCM) is caused by decreased myocardial compliance. The beneficial effect of verapamil in HCM is related to improved relaxation and diastolic filing. Verapamil is also effective in relieving myocardial ischemia. Beta-blockade decreases pressure gradient and oxygen consumption. Idiopathic restrictive cardiomyopathy is a very rare disease and decreased myocardial compliance is responsible for CHF.

We investigated the signal transduction of serotonin secretion by stimulation with DNP-Ascaris antigen or ionomycin in rat basophilic leukemia cells (RBL-2H3). The modes of action of antigen and ionomycin for serotonin secretion were shown to be similar. The treatment of cells with antigen resulted in increased tyrosine phosphorylation of 105 and 72 KDa proteins, in particular, the tyrosine phosphorylation of 72 KDa protein seemed to correlate with serotonin secretion. Furthermore, we observed that antigen stimulation caused a marked increase in inositol polyphosphates production, which derived from the tyrosine phosphorylation of phospholipase C-gamma in RBL-2H3 cells. On the other hand, treatment with ionomycin also resulted in an increase in tyrosine phosphorylation of 72 KDa protein, but did not induce inositol polyphosphates production. These results suggested that the activation of tyrosine kinase may be related to serotonin secretion, and that intracellular Ca2+ increase may also play an important role in this activation.

The crucial issues in the management of congestive heart failure (CHF) are improvement of depressed myocardial contractility and reduction of excessive load. For this purpose, positive inotropic agents and vasodilators have been developed as new oral drugs. The former include Denopamine which possesses beta 1 stimulating effect, Xamoterol which is a unique agent acting as a beta 1-partial agonist, and Ibopamine, Docarpamine and Phosphodiesterase Inhibitors which possess both inotropic and vasodilating effects and are called "Inodilators". The latter include Angiotensin Converting Enzyme Inhibitors. In addition, new vasodilators, such as, Vasopressin Antagonist have also been developed. However, careful long-term clinical trials are required with regard to the efficacy and adverse effects before these agents are widely used with safety in the management of CHF.

It is sometimes very difficult to diagnose dissecting aortic aneurysms (DAA), particularly in its early stage, due to manifold signs and symptoms. The purpose of this study is to clarify the reasons for such erroneous diagnoses. A total of 41 patients with DAA were referred to our hospitals for further examination and/or surgery from April 1986 to August 1989. In 18 of these patients, the diagnostic possibility of an underlying DAA was overlooked by the referring physicians. Among these 18 patients, 2 were mistakenly diagnosed as uncomplicated myocardial infarction (MI), one as pneumonia, 2 as cerebral infarction, 6 as acute abdominal disease, one as cholelithiasis, 5 as thrombosis of the lower extremities, and one as malignant metastasis to the pericardium. The following is the detail: In 2 cases thought to be uncomplicated MI, an expanding dissecting ascending aorta had crushed the lumen of the left coronary artery, causing MI, in turn, wasting clinical treatment and consuming precious time. In one case, enlargement of the descending aorta on the chest radiography was overlooked and the patient's symptoms were mistakenly attributed to pneumonia. In 2 cases in which symptoms of cerebral ischemia were thought to be attributed to cerebral thrombosis, the real cause turned out to be occlusion of the brachiocephalic artery following aortic dissection. Among 6 cases which were initially considered to have only acute abdominal disease, 3 presented with symptoms and signs of ileus, and their exploratory laparotomies yielded no positive findings.(ABSTRACT TRUNCATED AT 250 WORDS)

We presented a new method of catheter implantation by puncturing the left axillary artery directly under ultrasound guidance. This method was easy and non-invasive comparing with previous methods. Fifteen patients with advanced cancers were treated with infusion chemotherapy using this method and no severe complication was observed. Therefore, it was considered that our new procedure was beneficial for the management of patients with advanced cancers.