Poly I:C-induced expression of intercellular adhesion molecule-1 in intestinal epithelial cells.

Intercellular adhesion molecul-1 (ICAM-1) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily of adhesion molecules and plays perdominant roles in recruitment and trafficking of leucocytes to sites of inflammation. ICAM-1 expression in intestinal epithelial cells (IECs) is enhanced by several stimuli, such as proinflammatory cytokines, bacterial infections or pathogen-associated molecular patterns. One of these stimuli, double-stranded RNA (dsRNA), is a by-product of viral replication and can be recognized by its cognate receptor Toll-like receptor 3 (TLR-3). In spite of expression of both TLR-3 and ICAM-1 in IECs, correlation between TLR-3-signalling and ICAM-1 expression has never been examined in IECs. In the present study, we investigated whether poly I:C, an analogue of dsRNA, can stimulate the expression of ICAM-1 in IEC line, HT-29. Poly I:C-stimulation up-regulated the expression of ICAM-1 mRNA by real-time polymerase chain reaction. Enhanced expression of ICAM-1 was confirmed in protein level by immunofluoresense cell staining and enzyme-linked immunosorbent assay by measuring the released soluble ICAM-1 in culture supernatant. As the stimulation effect was reduced by pre-treatment of the cells with anti-TLR-3 antibody, poly I:C-binding signal was thought to be sensed by TLR-3 on the surface of HT-29. The results of luciferase assay and nuclear factor kappa-b (NF-kappaB) inhibitor treatment experiments indicated that the downstream signal was mainly transduced by transcription factor, NF-kappaB. All these results demonstrated the connection between TLR-3 signalling and ICAM-1 expression in HT-29 cells and indicated the importance of coordinated function of both innate and adaptive immunity against viral infections.

Effect of famotidine on recurrent bleeding after successful endoscopic treatment of bleeding peptic ulcer.

AIM: We investigated the effect of acid suppression therapy on recurrent bleeding after successful endoscopic treatment of bleeding peptic ulcer. METHODS: A total of 400 patients with bleeding peptic ulcer received either intravenous infusion of famotidine (40 mg/day) (n = 207, 163 males, 44 females, mean age 61.5 years) or drip infusion of omeprazole (40 mg/day; n = 193, 134 males, 59 females, mean age 59.8 years) after successful endoscopic treatment. The fasting duration, hospital stay, volume of transfused blood, incidence of rebleeding and mortality were compared between the two groups. RESULTS: The incidence of rebleeding did not differ significantly between the famotidine group (9%) and the omeprazole group (8%). The mean hospital stay was significantly shorter in the omeprazole group (18.4 days) than in the famotidine group (21.5 days, P = 0.009). However, there was no statistically significant difference in fasting duration, volume of transfused blood or mortality. CONCLUSION: Our findings indicate that intravenous infusion of famotidine after successful endoscopic treatment is equivalent to drip infusion of omeprazole for prevention of recurrent bleeding.

Improvement in gastric histology following Helicobacter pylori eradication therapy in Japanese peptic ulcer patients.

We aimed to determine if successful or failed eradication of Helicobacter pylori with triple therapy causes any difference in gastric mucosal histology. Japanese H. pylori-positive patients with a healed peptic ulcer received high (n = 112) or low (n = 113) doses of triple therapy (omeprazole, amoxicillin and clarithromycin) for 1 week. Biopsies from the greater curvature of the central antrum and upper corpus were taken 6 weeks and 30 weeks after treatment completion, and gastric mucosal histology compared between successful (n = 171) and failed (n = 34) eradication groups. Morphological variables of gastritis were graded according to the updated Sydney System. Successful eradication therapy was defined as improvement in inflammation, neutrophil activity and atrophy; failed eradication therapy as improvement in inflammation and neutrophil activity only. Gastric mucosal atrophy gradually improved (in addition to improvements in inflammation and neutrophil activity) with successful eradication of H. pylori infection.

Influence of exercise on QT dispersion in hypertensive patients with left ventricular hypertrophy without coronary artery disease.

In hypertensive patients with left ventricular hypertrophy (LVH), the influence of exercise on the regional variations in ventricular repolarization is not well understood. The present study compared dispersions of QT and QT apex (QTD and QTaD), which are indices of regional variations in ventricular repolarization, between hypertensive patients with echocardiographic evidence of LVH and those without LVH. Seventy essential hypertensive patients underwent a modified Bruce protocol exercise test, and QTD and QTaD were measured at rest and at peak exercise level. All subjects had undergone coronary angiography and did not have coronary artery disease. None of them showed ST-segment depression during or after exercise. There were 20 patients with LVH and 50 patients without LVH. The QTD and QTaD at rest were not different between the patients with LVH and those without LVH (56+/-32 vs 57+/-28 ms, 52+/-20 vs 49+/-23 ms). At peak exercise level, QTaD was significantly decreased compared with the baseline in hypertensive patients without LVH (49+/-23 to 42+/-16ms, p<0.05), whereas in patients with LVH QTaD increased (52+/-20 to 67+/-17ms, p<0.05). QTaD at peak exercise level was positively correlated with the left ventricular mass index (r=0.357, p=0.0024). These data were unchanged after correction for heart rate using Bazett's equation. In conclusion, QTaD increased after exercise in hypertensive patients with LVH. Inhomogeneity of repolarization is induced by exercise stress in hypertensives with LVH.

Significance of exercise QT dispersion in patients with coronary artery disease who do not have exercise-induced ischemic ST-segment changes.

The poor sensitivity and the poor predictive value of ST-segment depression have limited the usefulness of the exercise electrocardiogram (ECG) in the diagnosis and evaluation of coronary artery disease (CAD). The QT dispersion (QTD), recorded as the difference between maximal and minimal QT intervals on a 12-lead exercise ECG, is sensitive to myocardial ischemia and may improve the accuracy of exercise testing in patients with CAD who do not show an ST-segment depression. Exercise ECGs were analyzed in 50 subjects who had undergone coronary angiography for clinical indications. None of them showed an ST-segment depression during or after exercise: There were 25 patients with significant coronary artery stenosis and 25 without significant stenosis. The QTD measured before, immediately after, and 1 min after exercise was similar in the 2 groups. The QTD at 3 and 5 min after exercise was significantly greater in patients with CAD than in the controls, and the most marked difference in QTD was observed at 3 min after exercise. A QTD at 3 min after exercise of >60 ms had a sensitivity of 80% and specificity of 88% regarding the diagnosis of CAD. When a deltaQTD (post-exercise QTD minus QTD at rest) at 3 min after exercise of >0 ms was added to a QTD of >60 ms as a condition for positivity, the specificity increased to 96%. QTD measured at 3 min after exercise increases the accuracy of exercise testing in patients with CAD who do not show an ST-segment depression.

[Regional cerebral blood flow and cerebrospinal fluid amino acid analysis in elderly dementia].

Regional cerebral blood flow and amino acid concentration in the cerebrospinal fluid were studied in 12 cases of vascular dementia, 12 cases of Alzheimer's disease, 12 cases of chronic alcoholism, and 12 age-matched healthy controls. In vascular dementia, blood flows were decreased in the cerebral cortex, frontal white matter, thalamus, caudate nucleus, and putamen and alpha-aminobutyric acid and glutamic acid concentrations were increased in the cerebrospinal fluid. In Alzheimer's disease, blood flows were decreased in the frontal cortex, parietal cortex, temporal cortex, and frontal white matter and alanine concentration was increased in the cerebrospinal fluid. In chronic alcoholism, blood flows were decreased in the cerebral cortex, thalamus, and putamen and urea, alanine, and glycine concentrations were increased in the cerebrospinal fluid.

[Clinical evaluation of FemoStop in arrest of hemorrhage of the femoral artery].

A new device, FemoStop, in which the compression bag is replaced with a translucent one made of polyethylene for easy inspection, was used in 74 patients (76 examinations) who underwent angiography, including the setting of indwelling catheters in 10 patients, to obtain an easy and reliable maneuver for arresting hemorrhage at the puncture site. No failure in arrest of hemorrhage was recognized, and complications such as hematoma and re-bleeding were nonexistent. The doctor's time required for the arrest of hemorrhage was less than 5 minutes. On the other hand, in a beginner using the conventional manual compression method in 74 patients (74 examinations), the rate of failing to arrest hemorrhage was 5/74 cases, small hematoma was seen in three cases, re-bleeding occurred in one, and the time required for arrest was about 20 minutes. In conclusion, FemoStop was clinically useful for beginners.

Autologous bone marrow transplantation in children with advanced neuroblastoma.

BACKGROUND: Encouraging results have been reported with high dose chemotherapy and total body radiation followed by bone marrow autotransplantation in children with advanced neuroblastoma; however, relapse remains a significant problem. METHODS: The authors treated 22 children with advanced neuroblastoma with high dose chemotherapy, surgery, intraoperative radiation, and a bone marrow autotransplant (treated in vitro to remove tumor cells) followed by 13-cis-retinoic acid. RESULTS: The 3-year relapse rate was 25% (95% confidence interval [CI], 6-44%). The 3-year disease free survival rate was 72% (95% CI, 52-92%). Toxicities included hemolytic uremic syndrome, herpes infection, and hepatic venoocclusive disease. CONCLUSION: These data suggest that this treatment strategy offers an increased rate of 3-year disease free survival. The nonrandomized nature of this study and its use of multiple modalities precludes the analysis of the specific contribution of each treatment component and comparison with conventional therapy.

[Results of electron beam irradiation for tongue cancer].

One hundred and eighty three patients with squamous-cell carcinoma of the tongue were treated with electron beam irradiation at the Dept. of Radiology, Nihon University School of Medicine, from 1967 to 1988. We analyzed the therapeutic results of the investigation to find out indications of squamous-cell carcinoma of the tongue to see if it could be treated by intra-oral cone irradiation with electron beam (IOC). The patients were restaged, as follows: stage I, 38 cases: stage II, 64 cases: stage III, 58 cases: stage IV, 23 cases. There were 113 males and 70 females, ranging in age from 18 to 87 years old. IOC was applied for T 1 or smaller T 2 cases. External neck irradiation and IOC were combined for larger T 2, T 3 or T 4 cases. The two-year local-control rates for primary lesions with the present method were 85% for T 1, 73% for T 2, and 58% for T 3. There were no two-year local-control cases for T 4. Clinical feature of the tumor were classified into tumourous type, small ulcerating type, and large ulcerating type. The two-year local-control rates were as follows: 80% for tumorous types, 68% for small ulcerating types and 53% for large ulcerating types. Uneven fractionated irradiation was performed on 144 cases and even fractionated irradiation was performed on 39 cases. The two-year local-control rates were as follows: 68% for uneven fractionated irradiation cases, 61% for even fractionated irradiation. In T 2 and T 3 cases, the two-year local-control rates were as follows: 77%, 63% for uneven fractionated irradiation cases, 56%, 40% for even fractionated irradiation cases. The two-year local-control rates were increased by uneven fractionated irradiation for T 2, T 3 cases (P < 0.05). We analyzed the therapeutic results in details for T 3 cases. T 3 patients were classified into two categories according to tumor size (category 1: long axis X short axis > 1000mm2: category 2: long axis X short axis < or = 1000mm2). The two-year local-control rates were 48% for category 1, and 72% for category 2. T 3 patients were classified into two categories according to clinical feature of the tumor (tumors with ulcers and tumors without ulcers). The two-year local-control rates were 43% with ulcers, and 74% without ulcers. The actuarial five-year survival rates were 92% for stage I, 72% for stage II, 67% for stage III, and 12% for stage IV.(ABSTRACT TRUNCATED AT 400 WORDS)

[Multi-institutional trials of radiation and Furtulon combination therapy for malignant tumors].

The efficacy of the response and safety in combination therapy of radiation and furtulon, a derivative of fluoropyrimidine, for malignant tumors were tested on a multi-institutional basis. Patients in this study were given daily 800 mg of oral furtulon and also irradiations. Twenty-three out of 30 evaluable cases showed CR or PR response (response rate was 77%). The response rates of the cases classified into regions of primary sites were 67% of stomach (4/6), 57% of colorectum (4/7), 100% of breast (9/9), 67% of esophagus (4/6), 100% of ovary (1/1) and 100% of lung (1/1). Four out of 36 cases were not given the full scheduled treatments due to grade 3 side effects, consisting of one diarrhea case suspected due to furtulon side effect, 2 impaired general condition cases according to the progression of diseases, and one case showing radiation dermatitis, dysphagia due to radiation mucositis and leukocytopenia. These results show that the combination therapy of radiation and furtulon is an efficacious and safe modality for primary and metastatic tumors.

[Uneven fractionation irradiation].

To get the better therapeutic ratio with low LET radiation therapy alone, the improvement of the physical dose distribution and the mode of dose fractionation are required. Since 1972, uneven fractionation irradiation with electron beam has been used for head and neck tumors. The 2 year control rates for primary tongue cancer T1, T2 and T3 by this method were approximately comparable to that of the small source implantation. In the treatment results for the cervical lymph node metastasis, uneven fractionation technique is superior to conventional one. Furthermore, this results was reviewed by means of multivariate analysis.

Effects of prophylactic irradiation of acute lymphoblastic leukemia in the central nervous system of children.

The development of prophylactic therapy for acute lymphoblastic leukemia (ALL) in the central nervous system in children has resulted in an improvement of the prognosis and prolongation of patients' lives. On the other hand, late irradiation effects have increased with the improvement of the prognosis. Therefore, there is now an important need to lessen these late effects without deteriorating the prognosis. We have investigated the recurrence rate, the survival rate and the cause of death of ALL patients who were divided into a none prophylactic irradiation group and 15 Gy, 20 Gy and 24 Gy irradiation groups. The results show that the effect of prophylactic irradiation has been more effective in the 20 Gy group than that of the 24 Gy group. Furthermore, brain atrophy and leukoencephalopathy, which were investigated by X-ray CT in long-term survivors of post-prophylactic irradiation without recurrence, have been less in the 20 Gy group than in that of the 24 Gy group. This report presents the result that the most favorable dose for prophylactic irradiation for central nervous system leukemia of ALL in children is 20 Gy by a step-up method.

Antral gastrin and somatostatin concentrations in peptic ulcer patients.

As an attempt to approach the pathogenesis of peptic ulcer disease, antral gastrin and somatostatin concentrations were studied in normal subjects, patients with duodenal ulcer and gastric ulcer. In the patients with peptic ulcer, antral somatostatin concentrations were significantly lower than those in normal subjects. In non-ulcer subjects, including normal subjects and patients with atrophic gastritis, antral somatostatin concentrations were correlated inversely with the degree of antral gastritis, while in the patients with peptic ulcer, especially in duodenal ulcer, they were low, irrespective of histological picture of antral mucosa. In the patients with duodenal ulcer, low antral somatostatin concentrations with high antral gastrin/somatostatin ratio may cause increased serum gastrin levels and increased gastric acid secretion. From the above findings, it has been concluded that low antral somatostatin levels may be related to the pathogenesis of duodenal ulcer disease.