Comprehensive treatment of advanced neuroblastoma involving autologous bone marrow transplant

Encouraging results are reported with high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation in the treatment of advanced neuroblastoma. However, relapse remains a significant problem. We used high-dose chemotherapy, surgery, intraoperative radiation and an autologous bone marrow transplant treated in vitro to remove tumor cells followed by 13-cis-retinoic acid to treat 36 children with advanced neuroblastoma. This comprehensive treatment appears to improve the survival rate of patients with advanced neuroblastoma, including those with N-myc amplification and bony involvement. The disease-free survival rate was 66% (95% confidence interval, 49–84%) at 3 years. All patients who received 13-cis-retinoic acid developed cheilitis, but no bone marrow depression occurred in these patients. Five patients developed hemolytic uremic syndrome (HUS) post-transplant. This may have been related to the procedure used for total body irradiation. Patients who had their kidneys shielded during this procedure did not develop this syndrome. Patients who received local irradiation at the primary site showed no evidence of relapse in this region, indicating that such therapy may help to prevent a relapse. These data suggest a high rate of 3 year disease-free survival with this treatment strategy. The nonrandomized nature of the study and use of multiple modalities precludes analysis of the specific contribution of each.     

Clinical and Endoscopic Study of Ischemic Colitis

The clinical signs and symptoms of ischemic colitis have been analyzed. Eighty-one cases were investigated; there were 62 cases of the transient type, 15 of the stricturing type, and 4 cases of the gangrenous type. All cases were diagnosed by colonoscopy. In addition, the healing process of the transient type, observed by colonoscopy, was analyzed. The results were noted as follows. 1. Sudden onset of abdominal pain was the initial complaint in most of the cases. The onset time of this pain was morning (8.7%), afternoon (23.2%), and night (68.1 %). 2. The average amount of time from the onset of abdominal pain to hemorrhage was 6.6 +/- 4.1 hours. Abdominal pain persisted for 1.6 +/- 0.7 days and hemorrhage continued for an average of 1.5 +/- 0.8 days. 3. The transient type was common in the young age group (under 40), and the stricturing type was common in the advanced age group (over 70). 4. In cases of the transient type, the lesions healed within 7 days in 68% of all cases, and within 14 days in 82% of them. On the other hand, in cases of the stricturing type, during these same time spans, the lesions healed in 33% and 50% of affected patients, respectively. 5. The change in the findings of longitudinal ulcers in cases of the transient type, which were typical findings of ischemic colitis, disappeared within about 6 days in most cases. It is concluded that an emergency colonoscopy is essential in the diagnosis of ischemic colitis of the transient type.     

A Study on Atypical Endoscopic Findings of Ulcerative Colitis: Longitudinal Ulcers,Mucosal Bridges and Red Spots

Abstract: One hundred and twenty-one ulcerative colitis patients diagnosed during the period of 1984 to 1988 were examined endoscopically on repeated occasions. Forty-six patients had total colitis, 56 had left-sided colitis, 15 had proctitis, and 4 were postoperative patients. When classified according to their macroscopic findings, 28 of the patients had the polyposis type of this disease, 88 had the atrophic type, and 5 had the mixed type. Longitudinal ulcers were found in 9 patients, occuring usually in the sigmoid colon. There was no pathological evidence of ischemic changes in these 9 patients. Mucosal bridges were found in 13 of the patients with total colitis, occurring somewhere from the cecum to the rectum. The mucosal bridges tended to be present during the mildly active stage of the disease. Red spots, which sometimes looked like vascular spiders, were found in 10 patients. The spots tended to appear before the disease went into the inactive stage. Histological observation showed regenerating vessels, sometimes with intramucosal bleeding; therefore the spots seemed to be intractable changes.     

A comparison of the dissolution rates of caffeine tablets in a rotating-basket with those in a Sartorius dissolution tester

Uncoated caffeine tablets of four different hardnesses were tested for dissolution rate by the Sartorius (S.S. method) and by the rotating basket method of the U.S.P. XVIII. In both methods the dissolution rate decreased with increasing hardness, and the rate obtained with the S.S. method was always less than that by the U.S.P. method. This result cannot be explained as being due only to the difference in the volume of dissolution medium. Also it was difficult to ensure that the characteristic changes in the process of dissolution paralleled the curves obtained from a plot of % caffeine dissolved vs time. Accordingly, the dissolution rate constants were calculated from the slope of each straight line in a plot of In W^∞/(W^∞ - W) vs time.     

Validity of kissing gastric ulcers induced in rats for screening of antiulcer drugs

Abstract We examined the validity of kissing gastric ulcers induced in rats by determining the effects of conventional antiulcer drugs. Gastric ulcers were produced by luminal application of 60% acetic acid (0.2 mL, 45 s) to an area clamped with a pair of forceps. The ulcers were evaluated as to either the ulcerated area (mm²) or ulcer index (ulcerated area x depth). The healing of kissing ulcers was significantly enhanced by 2 week treatment with oral omeprazole (10, 30 mg/kg per day), leminoprazole (30, 60 mg/kg per day) or cimetidine (300, 450 mg/kg per day). The rate of healing was > 50% to both the ulcerated area and ulcer index. Aluminium hydroxide (up to 1800 mg/kg per day) had no effect on ulcer healing on the ulcerated area, but it caused a significant reduction in the ulcer index. Gastric acid secretion was significantly inhibited by repeated administration of omeprazole, leminoprazole and cimetidine in a dose-dependent manner. Aluminium hydroxide significantly increased the pH of the gastric contents. The mechanism of action of these drugs appears to involve partly the inhibition of gastric acid secretion and neutralization of secreted acid. We conclude that kissing gastric ulcers are a sensitive ulcer model for the screening of antiulcer drugs.     

An Endoscopically Resected Case of Early Carcinoma of the Duodenal Bulb

We report here on a case of early carcinoma originating in the duodenal bulb. The patient was a 70-year-old woman who complained of nausea. A gastrointestinal endoscopy disclosed a lesion protruding from the duodenal bulb and a biopsy revealed adenocarcinoma. According to the results of the endoscopy, the tumor was subpedunculated and probably confined in the mucosal layer. Based on these findings, we performed an endoscopic tumor resection. A histological examination of the resected specimen revealed a papillotubular adenocarcinoma (1.7 × 1.2 × 0.8 cm) localized in the mucosal layer. No carcinomatous lesion was left in the resected margin. No symptoms of recurrence have been noted during the last 6 months. When considering clinical pathology of the present case, we assessed 39 cases of primary early carcinoma in the duodenal bulb previously reported in the Japanese literature. We considered that our patient was the 14th in Japan with an early carcinoma of the duodenum which was completely excised via endoscopic resection. We expect that endoscopic resection of early duodenal carcinoma will be widely used in the future.     

Difference in Prognosis between T- and B-Cell Lymphomas: Clinical Study at Shikoku Cancer Center Hospital

In order to determine whether the surface marker phenotypesof non-Hodgkin's lymphomas affect the prognosis, we have studiedthe differences in response rate and duration of survival betweenT- and B-cell lymphomas. Sixty-four patients who underwent first-linetherapy, including combination chemotherapy and/or radiotherapy,from February 1979 to August 1985 were evaluated. With the aidof standard immunological methods and monoclonal antibodiesrelated to T-cells and B-cells. 21 T-cell lymphomas and 21 B-celllyrnphomas were identified. In the other 22 cases phenotypeswere not determined mainly because of the inability to obtainfresh samples. The complete remission rate was 100% for B-celllymphomas and 52.3% for T-cell lymphomas. The median survivaltime for patients with lymphomas of Stage III and IV. excludingthose with low-grade histology, was nine months for T-cell lymphomasand 17 months for B-cell lymphomas. T-cell lymphomas were foundto have significantly poorer prognosis than B-cell lymphomas.One patient with B-cell lymphoma and six patients in an undeterminedphenotype group, who were treated with combination chemotherapy,have been alive more than three years without relapse and thesepatients are considered potentially cured. Our results suggestthat the surface marker phenotype study of lymphoma cells aswell as histological subtying is important in prognosis andthat more effective therapy is needed to improve the prognosisof T-cell lymphomas.     

Characterization of a novel cell damage model induced by acid and pepsin using rat gastric epithelial cells: Protective effect of sucralfate

We have established a new model for rat gastric epithelial cell (RGM1) damage caused by both acid and pepsin. Exposure of RGM1 to an acidified medium (pH 3.5–5.0) for 10-50 min decreased cell viability in a time- and pH-dependent manner. Pepsin (0.5–1.0 mg/mL) at pH 4.5 potentiated cell damage in a concentration-dependent manner. Based on these results, two types of cell damage models caused by incubation of cells at pH 4.0 and with pepsin (0.75 mg/mL) at pH 4.5 for 30 min, respectively, were established. The intracellular pH (pH) gradually decreased with a decrease in medium pH and an increase in exposure time. At pH ≤ 4.0, pH_i reached approximately pH 6.3. Pepsin at pH 4.5 caused a further reduction in pH_i compared with the acidified medium alone. Pepsin pre-incubated with pepstatin did not induce any cell damage. Pretreatment with sucralfate (0.1 -3 mg/mL) for 2 h significantly prevented cell damage caused at both pH 4.0 and with pepsin at pH 4.5 in a concentration-dependent manner. Sucralfate (3 mg/mL) significantly prevented the reduction in pH_i at pH 4.0 or with pepsin at pH 4.5. 16,16-Dimethyl prostaglandin E₂ (30 μg/mL) had no effect on either cell damage or pH_i. These cell damage models involving RGM1 are useful for studying the mechanism underlying cell damage and for the screening of cytoprotective drugs.