Dynamics of microbial populations and strong selection for Cycloclasticus pugetii following the Nakhodka oil spill.

Microbial population changes were monitored immediately after the Nakhodka oil spill accident in January 1997 at the heavily oil-contaminated Mikuni coast along the Sea of Japan. The total cell number was almost stable for one year at 2-5 x 10(5) cells mL(-1), while the relative occurrence of culturable heterotrophs and degraders of oil components such as C-heavy oil, kerosene, and n-tetradecane varied, showing a maximum (>50% of the total) immediately following the accident. Gene amplification and phylogenetic analysis of a dilution culture using C-heavy oil as the sole carbon and energy source revealed that one of the predominant oil degraders at the oil-contaminated coast in 2 weeks after the accident closely resembled the aromatic hydrocarbon decomposer Cycloclasticus pugetii. Microbial community composition in oil-contaminated seawater was estimated at the molecular level using newly developed oligonucleotide probes, probe wash-off curve estimation, and quantitative fluorescence dot-blot hybridization techniques. At two different oil-polluted sites, harbor and intertidal regions, the C. pugetii group was estimated to make up 23-25% of the total Bacteria population, followed by the aliphatic hydrocarbon decomposer Alcanivorax borkumensis, which formed 4-7% of the Bacteria. In incubation experiments using floated oil slick and indigenous microbes collected at the harbor, oil degradation activities were enhanced by the addition of both organic and inorganic nutrients. Significant decreases were found in aromatic and aliphatic hydrocarbon fractions: 54-60% and 22-24% in 2 weeks to 68-77% and 23-32% in 2 months, respectively.

Apoptosis and p53 overexpression in human rectal cancer; relationship with response to hyperthermo-chemo-radiotherapy.

Hyperthermo-chemo-radio (HCR) therapy has been found to be effective for rectal cancer. Biomarkers for predicting the effect of HCR therapy are important in determining optimum treatment regimens. Hyperthermo-chemo-radiotherapy (HCR therapy), consisting of hyperthermia at 42 degrees C to 45 degrees C for 40 minutes (twice per week for two weeks), a total of 60 Gy irradiation and administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) (total 8400 mg), were prescribed pre-operatively for 29 patients with rectal cancer, using tissue specimens collected at pre-treatment biopsy. Apoptosis and overexpression of p53 protein were investigated histopathologically and immunohistochemically. On termination of HCR therapy, all the tumors were surgically resected and effectiveness of the therapy was evaluated histologically. Spontaneous apoptosis was evident in the pre-treatment cancer tissues of 14 patients (48.2%). In this apoptosis-positive group, the positive rate of expression of the p53 protein (21.4%, 3 out of 14) was lower as compared to findings in the apoptosis-negative group (66.7%, 10 out of 15). The response to HCR therapy was better in the apoptosis-positive group than in the apoptosis-negative group. We propose that spontaneous apoptosis is closely related to the function of wild-type p53 protein and is also a predictive biomarker of the effect of HCR therapy for patients with rectal cancer.

Pneumonitis induced by ou-gon (scullcap).

A 53-year-old Japanese man with recurrent interstitial pneumonia was referred to us. The patient had taken a traditional herb medicine, otsu-ji-to, before the onset of pneumonia. A provocation test for each herbal ingredient contained in otsu-ji-to revealed that the pneumonitis had been induced by ou-gon (scullcap). Lymphocytosis with the CD8+ T-cell subset predominance was found in the bronchoalveolar lavage fluid and lymphocytic alveolitis was noted in the transbronchial lung biopsy specimen after the provocation test. Ou-gon, or scullcap, should be included in the list of drugs with definite causal association with pneumonitis.

Prognostic significance of lymphocyte infiltration following preoperative chemoradiotherapy and hyperthermia for esophageal cancer.

PURPOSE: Lymphocyte infiltration (LI) around cancerous lesions is an important immune response. The purpose of this study is to evaluate the prognostic significance of LI after preoperative treatment for esophageal cancer. METHODS AND MATERIALS: Preoperative chemoradiotherapy (CR therapy), either bleomycin 30 mg or cisplatin 120 mg/m(2) plus radiation 30 Gy, was performed on 51 cases with esophageal cancer, while hyperthermo-chemoradiotherapy (HCR therapy) was also indicated in 71 cases. Using resected specimens, both the histopathologic effectiveness and degree of LI to cancerous lesions were evaluated. RESULTS: The incidences of the cases in which preoperative treatment was effective were 56% and 92.3% in LI (-) and LI (++) group (p < 0.05). The presence of LI resulted in favorable prognosis; the 5-year survival rates of LI (++) and LI (+) patients were 75.5% and 46.1%, both of which were significantly better than LI (-) (27.8%, p < 0.05 and p < 0.01, respectively). Especially among cases whose preoperative treatment was moderately effective, a multivariate analysis revealed LI to be a favorable prognostic factor independent of other clinicopathologic factors (p = 0.0171). Regarding the preoperative treatment, the incidence of LI (++) was higher in the HCR group (16.9%) than in the CR group (2.0%, p < 0.01). CONCLUSIONS: LI appears to be a prognostic predictor after preoperative CR therapy while, in addition, simultaneous hyperthermia may stimulate LI in cases with esophageal cancer.

[Oral allergy syndrome in patients with Japanese cedar pollinosis].

Patients with pollinosis sometimes complain of oral symptoms (itching and tingling with or without edema of the lips, mouth and tongue) after eating fresh fruits and vegetables. This condition has been termed Oral Allergy Syndrome (OAS). Twenty-three patients with Japanese cedar pollinosis and OAS for fresh fruits and vegetables were included in this study. Their mean age was 31.3 years (range = 5 to 62). The fruits that caused OAS in these patients included melon, apple, peach, and kiwi fruit. Most patients with OAS exhibited hypersensitivity to more than two foods. Specific IgE antibodies to inhaled allergens of mite, Japanese cedar pollen, birch pollen, melon, apple, peach, and kiwi were evaluated using the Pharmacia CAP system. Eleven of the 16 subjects with specific IgE antibodies for birch pollen, did not suffer symptoms during the birch and alder pollen season. In subjects with specific IgE antibodies for fruits, 13 out of 20 patients showed specific IgE antibodies for apple, and 8 out of 9 patients with OAS for apples were also positive for specific IgE antibodies for apples. On the other hand, 17 patients had no specific IgE antibodies for melon, and only two patients and one patient showed specific IgE antibodies for kiwi fruit and peach, respectively. These results suggest that the evaluation of specific IgE antibodies to birch pollen and apple may be useful for diagnosing OAS in patients with Japanese cedar pollinosis.

Antiemetic effect of ramosetron during hyperthermo-chemo-radiotherapy for esophageal cancer.

BACKGROUND: The antiemetic effects of serotonin receptor antagonists during chemoradiotherapy for solid tumors have never been reported. We have developed hyperthermo-chemo-radiotherapy (HCR) for esophageal cancer. However, with this treatment, the more potent the chemotherapy was, the more frequently emesis was experienced. MATERIALS AND METHODS: Fifteen patients with esophageal cancer underwent HCR (6 courses of hyperthermia, cisplatin 20 mg/m2 x 6, 5-FU 300 mg/m2 x 15 and radiation 1.5 Gy x 30). Ramosetron was administered intravenously (0.3 mg x 15). The emesis inhibition rate was defined as the rate of patients having neither vomiting nor severe nausea. RESULTS: The incidence of patients without nausea gradually decreased to 60% at the end of chemotherapy. However, vomiting was completely avoided except in one patient for two days. The emesis inhibition rates of weeks 1, 2, 3 and 4 were 100.0, 93.3, 89.5 and 95.2%, respectively. The overall inhibition rate was 94.5% and the rate of "well inhibited" was 79.0%. There were no ramosetron-related adverse reactions. CONCLUSIONS: These findings suggest that ramosetron is a useful antiemetic agent for nausea and vomiting induced by chemoradiotherapy for solid tumors.

Mechanisms mediating the vasorelaxing action of eugenol, a pungent oil, on rabbit arterial tissue.

The inhibitory actions of eugenol on intracellular Ca2+ concentration ([Ca2+]i) and the contractions induced by excess extracellular K+ concentration ([K+]o) in rabbit thoracic aorta were investigated. Application of excess [K+]o solution (30-90 mM) produced contraction and increased the intensity of the Ca2+ fluorescence signal. Pretreatment with eugenol (> or =0.1 mM) reduced both the amplitude of contraction and the intensity of the Ca2+ fluorescence signal, but the contraction was more strongly affected than the [Ca2+]i. Application of eugenol (0.3 mM) to tissue precontracted by 90 mM [K+]o solution (immediately after the removal of the 90 mM [K+]o solution) slowed the decay of the [Ca2+]i signal, but it did not change the rate of relaxation. Carbonyl cyanide m-chlorophenylhydrozone (10 microM), a mitochondrial metabolic inhibitor, produced a reduction in tension despite a slight increase in [Ca2+]i when applied to muscle precontracted by 90 mM [K+]o solution. These results indicate that eugenol relaxes the rabbit thoracic aorta while suppressing the Ca2+-sensitivity and both the uptake and extrusion mechanisms for Ca2+. To judge from the similarities between its actions and those of metabolic inhibitors, eugenol may produce its actions at least partly through metabolic inhibition.

[A clinical study of inoperable head and neck cancers].

Thirty two patients with inoperable head and neck cancer seen at Jichi Medical School Hospital during the period 1978 to 1995 were analyzed. Distribution of the affected site was as follows: 15 cases of oropharynx, 12 of hypopharynx, and 3 of larynx. In order to study a better performance status, prognosis and side effects were compared between radiotherapy alone (17 patients) and combined radiochemotherapy (15 patients). Patients who received the combined therapy survived longer than those patients who received radiotherapy alone. Moreover, high QOL was obtained longer in the combined therapy. Therefore, we conclude that radiotherapy should be combined with chemotherapy for cases with inoperable head and neck cancer.

Disturbance of consciousness associated with hypophosphatemia in a chronically alcoholic patient.

A 69-year-old man with chronic alcoholism was admitted to our hospital due to disturbance of consciousness and oliguria. Emergency laboratory examination revealed metabolic acidosis, hypoglycemia, hyponatremia, mild liver dysfunction, acute renal failure and rhabdomyolysis. After administration of fluids and nutrients and continuous hemodiafiltration, he recovered from all signs and symptoms except for disturbance of consciousness after 7 days. Since severe hypophosphatemia persisted, we administered adequate phosphates, and then his level of consciousness normalized. We discuss the relationships among alcohol abuse, hypophosphatemia and disturbance of consciousness, and recommend that hypophosphatemia be considered a potential cause of disturbance of consciousness in alcoholic patients.

Relationship between the expression of HLA-DR antigen and the effectiveness of preoperative hyperthermo-chemo-radiotherapy in oesophageal cancer.

Based on the hypothesis that tumour cells expressing HLA-DR antigen would easily be damaged by the local immune response during preoperative treatments, the relationship was investigated between the expression of HLA-DR antigen in the oesophageal cancer and the effectiveness of the preoperative treatment. Immunohistochemical staining for the detection of HLA-DR antigen in cancer cells from biopsy specimens obtained before undergoing preoperative hyperthermo-chemo-radiotherapy (HCR therapy) in patients with oesophageal squamous cell carcinoma was performed, and the relationship between the expression of HLA-DR antigen and the effectiveness of HCR therapy was evaluated according to a histopathologic examination of resected specimen. A total of 35 cases were examined in which 14 showed strongly positive staining (+2), 14 weakly positive staining (+) and seven negative staining (-). No significant differences in the clinicopathologic factors between the groups were observed. In the 14 strongly positive HLA-DR antigen cases, nine were markedly effective (grade 3) (64.3%), four were moderately effective (grade 2) (28.6%) and one was slightly effective or ineffective (grade 1, 0) (7.1%). In the 14 weakly positive HLA-DR antigen cases, the markedly, moderately and slightly or ineffective cases numbered four (28.6%), eight (57.1%) and two (14.3%), respectively. On the other hand, in the seven patients showing no HLA-DR expression, the markedly, moderately and slightly effective cases numbered one (14.3%), two (28.6%) and four (57.1%), respectively. A statistical difference was observed between the cases of strongly positive and negative staining for HLA-DR antigen (p < 0.05). The expression of HLA-DR antigen in oesophageal cancer cells is thus considered to potentially be a valuable factor for predicting the effectiveness of preoperative treatment.

[Postoperative management of the preserved rectal segment in patients with familial polyposis: the use of 5-fluorouracil suppositories and green tea extract to inhibit tumor growth].

We report the clinical details of seven patients with familial polyposis. They underwent subtotal colectomy with ileorectostomy, and were treated with 5-fluorouracil suppositories and green tea extract after surgery. Some regression of the polyps in the preserved rectal segment was observed, and no rectal cancer developed in any of these patients.

Clinicopathologic features of patients with oesophageal cancer obtaining a histological complete response for preoperative hyperthermo-chemo-radiotherapy.

From 1979 to 1993, 151 patients with resectable oesophageal cancer underwent preoperative hyperthermo-chemo-radiotherapy (HCR) followed by a subtotal esophagectomy. All resected specimens were histopathologically evaluated, and then were classified into two groups according to the efficacy of the preoperative HCR. Group A included 33 patients whose resected oesophagus was free of any cancer cells (grade 3). Group B included 118 patients, in which viable cancer cells remained in the resected specimens to various degrees (grade 1,2). The incidence of patients with well differentiated squamous cell carcinoma, node negative cases, or TNM stage I/II was significantly higher in group A than in group B (27.3% versus 9.3%, 72.7% versus 50.8%, 72.7% versus 50.8%, respectively). The recurrence rate was 33.3% (11/33) in group A, while it was 65.3% (77/118) in group B (p < 0.005). There was no case with any local recurrence in the former, while it was 8.5% (10/118) in the latter. The 1-, 3- and 5-year survival rates were 87.2%, 65.9% and 46.1% in group A, while they were 54.8%, 26.7% and 18.8% in group B (p < 0.005), respectively. Preoperative HCR may be expected of decreasing in the recurrence rate, including regional relapse when a grade 3 is obtained. Complete local control would further positively influence the prognosis.

Recent advances in preoperative hyperthermochemoradiotherapy for patients with esophageal cancer.

BACKGROUND AND OBJECTIVES: Hyperthermochemoradiotherapy (HCR) has been performed on numerous patients with esophageal cancer. The purpose of this study is to demonstrate the recent advances in HCR. METHODS: From 1965 to 1997, 294 patients given preoperative chemoradiotherapy (CR) or HCR were classified according to the anticancer agent that was administered (CR; group A given bleomycin (BLM); group B given cis-diamminedichloroplatinum (II) (CDDP), HCR; group C given BLM; and Group D given CDDP). The local response and the long-term results were investigated. RESULTS: The cases in which CR or HCR was evaluated to be effective numbered 44 (48.4%) in group A, 22 (73.3%) in group B, 79 (63.7%) in group C, and 36 (73.5%) in group D. A significant difference was observed between groups A and B (P < 0.05). The highest incidence of markedly effective cases was observed in group D. The 5-year survival rates for the group A and B patients were 17.2% and 43.9%, respectively (P < 0.01), while the same rates for those of groups C and D were 25.6% and 57.8%, respectively (P < 0.05). Our results thus showed CDDP to have a greater effect than BLM, while HCR had a greater effect than CR. CONCLUSIONS: Preoperative HCR has improved thanks to recent advances in anticancer agents.

[Long-term results of preoperative hyperthermo-chemo-radiotherapy (HCR) for patients with esophageal carcinoma invading neighboring structures (T4)].

PATIENTS: A total of 180 patients with esophageal carcinoma invading the neighboring structures (T4) were surgically treated by esophagectomy and reconstruction in the Department of Surgery II, Kyushu University from January 1965 to April 1997. Any of these cases with distant node metastasis and demonstrating organ metastasis or a combined resection of adjacent structures were excluded from this study. As a result, twenty-six patients treated with preoperative hyperthermo-chemo-radiotherapy (HCR Group), 39 treated either with preoperative radiotherapy or preoperative chemo-radiotherapy (R or CR Group) and 23 non-treated patients (Non-tx Group) were thus entered in this study. RESULTS: The 3-year survival rates after esophagectomy in HCR Group, R or CR Group and Non-tx Group were 26.5%, 0% and 9%, respectively, while the 5-year survival rate of the HCR group was 15.9%. The group with preoperative HCR thus showed a significantly more favorable outcome than R or CR Group and Non-tx Group. (p < 0.05). DISCUSSION: The significant difference observed in the prognosis was thought to be due to the reinforced effect of local regulation due to hyperthermia. Our data thus suggest that preoperative HCR contributes to the prolonged post-operative survival for carcinoma of the esophagus invading the neighboring structures.

Improved surgical results after combining preoperative hyperthermia with chemotherapy and radiotherapy for patients with carcinoma of the rectum.

PURPOSE: The aim of this study is to evaluate long-term results of preoperative hyperthermia combined with chemotherapy and irradiation (HCR therapy) in patients with carcinoma of the rectum. METHODS: Postoperative prognoses were compared among 36 patients with carcinoma of the rectum, who were given preoperative HCR therapy followed by surgery, and 52 patients undergoing surgery alone without any preoperative therapy. RESULTS: There were significant differences in the prognosis between patients given preoperative HCR therapy plus surgery and those having surgery alone, and five-year survival rates were 91.3 and 64 percent, respectively. Particularly, for patients with tumors invading beyond the muscularis propria and/or with positive lymph node metastasis, a significantly longer survival was obtained with HCR plus surgery than in surgery alone (86.5 vs. 50.9 percent and 92.9 vs. 51.7 percent, respectively). However, no significant differences were observed in the postoperative prognosis for cases with no lymph node metastasis and/or with tumors limited to the muscularis propria between these two groups. CONCLUSIONS: These data clearly demonstrated the effectiveness of preoperative HCR therapy for improving long-term results of patients with carcinoma of the rectum, especially those demonstrating an advanced stage of disease.

[Continuous infusion high-dose leucovorin with cisplatin and 5-fluorouracil for a recurrent oropharynx carcinoma].

Cisplatin and leucovorin heighten the activity of 5-fluorouracil by increasing the intracellular concentration of reduced folates. Therefore, we treated the recurrent oropharynx carcinoma case, who had received concurrent chemotherapy with low-dose cisplatin and radiotherapy, with continuous infusion high-dose leucovorin with cisplatin and 5-fluorouracil. Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2, days 1 through 5); 5-fluorouracil (600 mg/m2, days 2 through 6); and leucovorin (200 mg/m2, days 1 through 6) administered once about every 4 weeks. Three cycles were performed, and a complete response was achieved. Grade 3 to 4 mucositis, nausea-vomiting, anemia, neutropenia, and thrombocytopenia occurred. Continuous infusion high-dose leucovorin with cisplatin and 5-fluorouracil was effective for this recurrent head and neck carcinoma. However, one must be cautious when comparing this chemotherapy in terms of toxicity.