A prospective survey of delayed adverse reactions to iohexol in urography and computed tomography

We investigated 7505 inpatients who underwent intravenous urography or contrast-enhanced computed tomography to assess risk factors for delayed adverse drug reactions to iohexol, a non-ionic iodinated contrast medium. Focusing on delayed adverse reactions, all adverse events were prospectively investigated for 7 days after injection of iohexol. To explore the relevant risk factors, the relationship between occurrence of adverse reactions to iohexol and 17 different variables was evaluated by logistic regression analysis. To assess the influence of seasonal factors, adverse reactions were separately evaluated during two periods: February to April (the pollinosis period in Japan) and July to September (the non-pollinosis period). The prevalence of delayed adverse events and delayed adverse reactions was 3.5 and 2.8%, respectively, whereas the prevalence of adverse events and adverse reactions was 5.7 and 5.0%, respectively. Multivariate analysis showed that six parameters had a significant influence on delayed adverse reactions to iohexol, including (a) a history of allergy, (b) season, (c) radiographic procedure, (d) age, (e) concomitant surgery or other invasive procedures, and (f) concomitant medication. The prevalence of delayed reactions was lower than in previous large-scale studies. Significant risk factors included a history of allergy and performance of radiography during the pollinosis period, suggesting that allergy was involved in delayed adverse reactions. The type of radiographic procedure also had an influence. Electronic Publication     

Lung-heart weight ratio as a possible index of cardiopulmonary pathophysiology in drowning

The aim of the present study was to investigate the lung-heart weight ratio in fresh- and saltwater drowning (n=67 and n=75, respectively) as a possible index of cardiopulmonary pathophysiology, in comparison with acute myocardial infarction/ischemia (AMI, n=75) and asphyxiation (n=85). In drowning cases, the total value of the combined lung weight and the amount of pleural effusion was regarded as a possible total lung weight. The median value of the combined/total lung weight was the highest in saltwater drowning, which was followed by freshwater drowning, AMI and asphyxiation, showing a tendency to be mildly increased depending on the heart weight. The lung-heart weight ratio was significantly higher in fresh-/saltwater drownings (3.944+/-1.538 and 4.825+/-2.242, respectively) than in asphyxiation (2.846+/-1.042) and AMI (2.641+/-0.916) (P<0.0001), showing a tendency to be higher in saltwater than freshwater drowning. However, the value depended on the gender and age of the subjects, and the difference between freshwater drowning and asphyxiation was insignificant in females. These results suggested that the lung-heart weight ratio may be an index for investigating the influence of aspirated immersion medium in drownings.     

Comparative study on the chronology of third molar mineralization in a Japanese and a German population

In Germany, a sharp increase in forensic age estimations of living persons has been observed in recent years. German law defines four legally relevant age limits: 14, 16, 18 and 21 years. In these age groups, radiographic assessment of the mineralization status of third molars is of particular importance. So far, the influence of ethnicity on the mineralization rate has been insufficiently analyzed. A total of 3031 orthopantomograms of 1597 Japanese and 1434 Germans aged between 12 and 26 years were examined. The mineralization status of third molars was evaluated on the basis of the classification proposed by Demirjian. For the individual mineralization stages, the study presents the mean values and standard deviations (SD) separately for both populations and sexes. The majority of probands from both the Japanese and the German population achieved the C stage and the late G and H stages of third molar development at similar ages. Significant differences between Japanese and Germans were observed, however, with regard to the D, E and F stages defined by Demirjian. Japanese men and women achieved the D, E and F stages approximately 2-3 years later than German men and women. In addition to forensic age determination in living persons, the presented reference data can also be used for age estimations of unidentified deceased persons and skeletons.     

Favorable outcome of preoperative low dose chemoradiotherapy against muscle-invasive bladder cancer

To investigate the feasibility of preoperative low-dose chemoradiotherapy, 50 patients with localized muscle-invasive bladder cancer (T2-T4) were treated with concurrent cisplatin (100 mg/body x 2 courses) and pelvic irradiation (40 Gy). Among 20 patients (40%) who achieved clinical complete regression, 11 with solitary tumor underwent partial cystectomy because of advanced age, poor condition of the patients, or a reluctance to have radical surgery. Radical cystectomy was carried out in the remaining 39 cases (complete regression 9, partial regression 30). Pathologic T0 response (no residual tumor) was achieved in 18 (36%) of all the cases. Median follow-up was 19 months (range 2-59 months). Estimated 3-year disease-free survival was 75% for all patients and 100% for T0 responders. Local recurrence (2 patients) or distant metastasis (6 patients) developed in 8 of 32 patients with pathologic persistent tumor. All of the 11 patients (9 with T0 response and 2 with a small residual tumor nest) who underwent partial cystectomy were recurrence free for observation periods up to 59 months. Low-dose chemoradiotherapy is as effective as other neoadjuvant protocols and is applicable to high-risk patients. The bladder can be preserved by partial cystectomy in selected cases with clinical complete regression.     

The limited efficacy of methotrexate, actinomycin D and cisplatin (MAP) for patients with advanced testicular cancer

BACKGROUND: Combination chemotherapy of methotrexate, actinomycin D and cisplatin (MAP) is reported to be effective against gestational choriocarcinoma. METHODS: Eight patients with metastatic testicular cancer who had elevated beta-hCG were treated with MAP. They included three refractory cases and two relapsed cases. An additional three patients received MAP as part of the induction therapy. The MAP therapy consisted of methotrexate (10 mg/m2) on days 1-5, actinomycin D (0.01 mg/kg) on days 1-5 and cisplatin (70 mg/m2) on day 1. RESULTS: In all three refractory patients, MAP failed to achieve tumor marker normalization. However, the elevated tumor markers normalized after MAP in the two cases of relapse. Of these two, one patient relapsed again 7 months after MAP and was subsequently salvaged with high-dose chemotherapy. The other patient relapsed and died of the disease 30 months after receiving MAP. Of the three patients who received MAP as part of the induction chemotherapy, one with pure choriocarcinoma achieved tumor marker normalization after MAP and is still alive without disease progression. In the other two patients, MAP failed to achieve marker normalization and the patients received high-dose chemotherapy. The toxicities were mainly bone marrow suppression and mucositis, which were almost acceptable. CONCLUSIONS: The results demonstrated the limited efficacy of MAP as salvage therapy. In addition, the efficacy of MAP as part of induction chemotherapy was negligible. However, there might be some role for MAP as a salvage therapy for patients with pure choriocarcinoma.     

A report of two cases--two patients of the extremely advanced hepatocellular carcinoma have responded completely for a long time after a combination therapy consisting of arterial chemotherapy and injection of interferon-alpha

The prognosis of advanced hepatocellular carcinoma (HCC) is extremely poor. Patient 1 was a 43-year-old male with major portal tumor thrombi. He received combination therapy consisting of continuous arterial infusion (MTX 30 mg/m2, day 1, CDDP/5-FU 6 mg/m2: 250 mg/m2, day 1-14) and subcutaneous injection of IFN-alpha (500 x 10(4) U, 3 times a week, 4 weeks). Patient 2 was a 66-year-old male with major hepatic venous tumor thrombi. He received combination therapy consisting of continuous arterial infusion (5-FU 6 mg/m2: 250 mg/m2, day 1-14) and subcutaneous injection of IFN-alpha (500 x 10(4) U, 3 times a week, 4 weeks). Decrease in tumor was observed in both patients markers and marked regression of tumor was observed in both patients. They are still in complete response. This combination therapy is an effective strategy for advanced HCC.     

Surgical indication and significance of local therapy for first pulmonary metastases from colorectal cancer

We often observe pulmonary metastases in patients following advanced colorectal cancer, especially rectal cancer. The prognoses of LM3 patients and patients with histological v2 factor in the primary site were unfavorable. Surgery was not indicated in these cases. Some patients experienced rapid progression during the standby period for surgery. For the surgery group, we recommend systemic reexaminations after several months. Pulmonary resections for metastatic colorectal cancer are beneficial to the selected patients and 5-year survival rate was 52.6%. New pulmonary relapses were also encountered which were the cause of death among the surgical patients. Close follow-up and multimodal therapy including surgery contributed to longer survival for postoperative pulmonary metastatectomy patients with colorectal cancer.     

TS-1 and lentinan combination immunochemotherapy for advanced or recurrent gastric cancer: a preliminary report

The immunocompetence and nutritional state of patients with advanced or recurrent gastric cancer is low, making it important to conduct chemotherapy while at the same time improving or maintaining their immunocompetence and nutritional state. To reduce the side effects but not the antitumor effect of TS-1, a 2-week regime of TS-1, and 1-week drug-free interval, in combination with the immunotherapeutic agent lentinan (LNT) was started in 5 patients with advanced or recurrent gastric cancer. Toxicity, efficacy, immunocompetence and nutritional state were investigated preliminarily to examine whether or not usefulness of lentinan could be evaluated. The IAP tended to decrease. TS-1 and lentinan combination immunochemotherapy was able to be carried out safely in patients with advanced recurrent gastric cancer. In order to examine the usefulness of combined LNT, it is thought to be necessary to perform a randomized trial using toxicity and not only efficacy but QOL and immunological and nutritional parameters as indicators.     

Effective use of combination chemotherapy with paclitaxel and 5-fluorouracil in a case of non-resectable advanced gastric cancer

The patient was a 67-year-old man who had gastric cancer located in the posterior wall of the stomach and who underwent surgery on June 27, 2001. The operative finding was carcinomatous peritonitis in which the primary lesion was considered to be surgically unresectable. Therefore, only a probe laparotomy was performed. Under full informed consent, we performed combination chemotherapy with paclitaxel and 5-fluorouracil, 5-fluorouracil (600 mg/m2/day) was infused continuously for 120-hours (day 1-5) on administration and paclitaxel (60 mg/m2) was infused for 1.5 hours after premedication at day 8, 15 and 22 on an outpatient basis. After 2 courses of the chemotherapy, the tumor markers were reduced remarkably, ascites had completely disappeared, and abdominal lymph nodes had decreased. No serious adverse event was observed and the patient maintained good QOL throughout the treatment.     

Human wee1 kinase is directly transactivated by and increased in association with c-Fos/AP-1: rheumatoid synovial cells overexpressing these genes go into aberrant mitosis

Wee1 kinase downregulates the M-phase promoting factor, a complex of cdc2 and cyclin B kinase, that controls mitotic cell division. We isolated human wee1 kinase gene promoter and found that it contained one AP-1-binding motif in its promoter region (5'-CGAGTCA-3'; -823/-817), through which wee1 kinase gene was directly transactivated by c-Fos/AP-1. In rheumatoid synovial cells, wee1 kinase was increased in conjunction with the increase of c-Fos/AP-1 and the substrate of wee1, cdc2, was phosphorylated. The amount of wee1 and c-Fos and the phosphorylation of cdc2 were decreased after treatment of the cells with an inhibitor of AP-1, curcumin. A significant proportion of cultured synovial cells of the patients with rheumatoid arthritis, but not those of osteoarthritis, shifted to a tetraploid (4C) state upon long-term culture. Thus, human wee1 kinase gene is directly transactivated by and increased in association with c-Fos/AP-1, and rheumatoid synovial cells overexpressing these genes go into aberrant mitosis.