Direct observations of pure electron outflow in magnetic reconnection.

Magnetic reconnection is a universal process in space, astrophysical, and laboratory plasmas. It alters magnetic field topology and results in energy release to the plasma. Here we report the experimental results of a pure electron outflow in magnetic reconnection, which is not accompanied with ion flows. By controlling an applied magnetic field in a laser produced plasma, we have constructed an experiment that magnetizes the electrons but not the ions. This allows us to isolate the electron dynamics from the ions. Collective Thomson scattering measurements reveal the electron Alfvénic outflow without ion outflow. The resultant plasmoid and whistler waves are observed with the magnetic induction probe measurements. We observe the unique features of electron-scale magnetic reconnection simultaneously in laser produced plasmas, including global structures, local plasma parameters, magnetic field, and waves.

High-power laser experiment forming a supercritical collisionless shock in a magnetized uniform plasma at rest.

We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.

Magnetic reconnection driven by electron dynamics.

Magnetic reconnections play essential roles in space, astrophysical, and laboratory plasmas, where the anti-parallel magnetic field components re-connect and the magnetic energy is converted to the plasma energy as Alfvénic out flows. Although the electron dynamics is considered to be essential, it is highly challenging to observe electron scale reconnections. Here we show the experimental results on an electron scale reconnection driven by the electron dynamics in laser-produced plasmas. We apply a weak-external magnetic field in the direction perpendicular to the plasma propagation, where the magnetic field is directly coupled with only the electrons but not for the ions. Since the kinetic pressure of plasma is much larger than the magnetic pressure, the magnetic field is distorted and locally anti-parallel. We observe plasma collimations, cusp and plasmoid like features with optical diagnostics. The plasmoid propagates at the electron Alfvén velocity, indicating a reconnection driven by the electron dynamics.

Kelvin-Helmholtz turbulence associated with collisionless shocks in laser produced plasmas.

We report the experimental results of a turbulent electric field driven by Kelvin-Helmholtz instability associated with laser produced collisionless shock waves. By irradiating an aluminum double plane target with a high-power laser, counterstreaming plasma flows are generated. As the consequence of the two plasma interactions, two shock waves and the contact surface are excited. The shock electric field and transverse modulation of the contact surface are observed by proton radiography. Performing hydrodynamic simulations, we reproduce the time evolutions of the reverse shocks and the transverse modulation driven by Kelvin-Helmholtz instability.

Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer.

Long-term cancer survivors risk development of second primary cancers (SPC). Vigilant follow-up may be required. We report outcomes of 92 patients who underwent chemoradiation for unresectable stage III non-small-cell lung cancer, with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100 patient-years (95% confidence interval: 1.0-4.9).

Cisplatin-resistant human small cell lung cancer cell line shows collateral sensitivity to vinca alkaloids.

A cisplatin-resistant cell line, SBC-3/CDDP, was established from a human small-cell lung cancer cell line, SBC-3. The SBC-3/CDDP cells were 13.1-fold more resistant to cisplatin than the parent SBC-3 cells. We investigated the cellular changes of this cell line with regard to the development of resistance to cisplatin. The SBC-3/CDDP cells showed various characteristics as follows: a) increased intracellular glutathione and glutathione S-transferase content b) decreased intracellular accumulation of cisplatin, c) increased topoisomerase I activity and the same topoisomerase II activity as the parent SBC-3 cells, and 4) strong cross-resistance to the platinum analogues and mitomycin C, moderate cross-resistance to 7-ethyl-10-hydroxy-camptothecin (SN-38), 4-hydroperoxy cyclophosphamide, etoposide, Adriamycin and methotrexate, and collateral sensitivity to vinca alkaloids and 5-fluorouracil. From these observations, the SBC-3/CDDP cells could be useful as a well characterized cisplatin-resistant cell line, and the resistance pattem in this cell line will give us much information for eradication of cisplatin-resistant tumor cells.

[Effects of oxitropium bromide on exercise and lung function in patients with pulmonary emphysema].

Anticholinergic drugs have been reported to be effective in pulmonary emphysema. We studied the effects of the anticholinergic drug oxitropium bromide on exercise capacity and lung function in patients with this disease. We studied 11 men and 1 women, aged 69.3 +/- 4.5 yrs, in whom chest radiography showed pulmonary emphysema. Before and after the subjects inhaled two puffs of oxitropium bromide, they walked in a corridor for 12 minutes, and the distance they walked and spirometric data were recorded. FVC and FEV1 were significantly higher after inhalation of the drug. FEV1% did not change, and the distance walked increased slightly. We also studied symptoms and peak expiratory flow rate in 37 patients with pulmonary emphysema before and after the start of therapy with inhaled oxitropium bromide. Symptom scores of wheezing and sleep improved, and peak expiratory flows increased significantly. We conclude that inhaled oxitropium bromide can improve lung function and slightly increase exercise capacity in patients with pulmonary emphysema. These effects may be caused by bronchodilation-induced increases in FEV1 and FVC. Monitoring of peak expiratory flow in patients with pulmonary emphysema may be useful for evaluating the clinical effectiveness of oxitropium bromide.

[A case of cystic fibrosis in a Japanese student].

A 16-year-old boy was admitted to our hospital because of coughing, sputum, and exertional dyspnea. Seven months after birth cystic fibrosis had been diagnosed. The chest roentgenogram on admission showed diffuse reticulonodular shadows and overinflation. Pulmonary function tests revealed obstructive and restrictive impairment. Erythromycin and Lomefloxacin were administered by mouth, and aminoglycosides were administered by inhalation. His symptoms were alleviated, and he is now an outpatient. In Japan, cystic fibrosis is rare, and this patient is extremely rare because he has grown up to be a 16-year-old. In this case, low-dose and long-term erythromycin administration was very effective.

[Respiratory disease in the tertiary emergency hospital].

We studied treatment for respiratory emergencies over the past 11 years at our hospital, a tertiary emergency center. We supply intermediate management services to a general hospital. A total of 13,667 patients received tertiary emergency medical care (annual mean: 1243). Of these, 1592 had severe respiratory disturbances (11.5% of the total; 971 males, 621 females; annual mean: 143). The most frequently seen conditions were COPD, respiratory failure due to old pulmonary tuberculosis) 35.2%, mortality failure due to old pulmonary tuberculosis (35.2%, mortality rate: 29.7%), bronchial asthma (26.0%, mortality rate 9.6%), pneumonia (19.0%, mortality rate 20.4%), and pneumothorax (10.3%). Very few of the patients with bronchial asthma who arrived in cardiopulmonary arrest survived. Patients with interstitial pneumonia, paraquat lung, pulmonary obstruction, adult respiratory distress syndrome, and near-drowning all had poor prognoses, as did victims of attempted suicide by hanging and attempted murder by strangulation. About 25% of the patients required mechanical ventilation, and about half of those patients died. Changes in prehospital care and in care given after critical care is no longer needed are important in improving the prognoses for patients with respiratory emergencies.

Antitumor activity of platinum analogs against human lung cancer cell lines and tumor specimens.

Antitumor activities of five platinum analogs, including cisplatin, carboplatin, 254-S, DWA2114R, and NK121, were compared using five human lung cancer cell lines and 19 tumor specimens obtained from lung cancer patients. The antitumor activity was evaluated by determining the ratio of the maximum tolerated dose of each drug to the 70% tumor growth inhibitory concentration in a colony assay. Cisplatin was the most potent agent, followed by 254-S and carboplatin. DWA2114R and NK121 were less potent than cisplatin and 254-S. Cross-resistance to adriamycin was also investigated using an adriamycin-resistant small cell lung cancer subline, SBC -3/ADM30. SBC-3/ADM30 was 1.7- to 4.0-fold more resistant to cisplatin, carboplatin, NK121, and DWA2114R, than was the parent line, SBC-3, and the subline was 2.0-fold more sensitive to 254-S. Using SBC-3, in vitro combination effects of etoposide and cisplatin, carboplatin, or 254-S were evaluated by the median-effect principle. Synergism was noted when cisplatin and etoposide were combined at a fixed molar ratio of 1:1. Combination of carboplatin and etoposide showed an additive effect. The combination of 254-S and etoposide was antagonistic at low concentrations, but was markedly synergistic at higher concentrations. These data suggested the efficacy of 254-S in the treatment of lung cancer.

Mortality and morbidity in two-year disease-free survivors of small cell lung cancer after treatment with combination chemotherapy with or without irradiation.

We evaluated the long-term outcome of 148 patients with small cell lung cancer (SCLC) who had been entered into clinical trials of chemotherapy with or without thoracic and prophylactic cranial irradiation (PCI) between 1981 and 1987. Eighteen patients (12%) survived for 2 or more years. With a minimum follow-up of 4.5 years, 10 of the 18 patients who remained disease-free at 2 years are currently alive and free of SCLC. Seven of these 10 patients currently function as they did before diagnosis. However, three suffer from central nervous system changes of varying degrees in severity which appeared 2-3 years after PCI. Eight of the 18 patients who were disease-free at 2 years have died. Two died of isolated relapse in the brain at 3.6 and 4.2 years after initiation of chemotherapy. Five died of other malignancies while continuing their complete response to SCLC; two of non-small cell lung cancer, two of acute myelogenous leukemia, and one of hepatocellular carcinoma. Another patient died of an unrelated disease without any evidence of SCLC. A small but substantial proportion of patients who underwent intensive treatment will achieve long-term survival; however, these patients remain at higher risk for second cancers and late toxicities. Therefore, attention must be directed to defining the safest way to employ such treatment in the management of SCLC.

[In vitro comparison of podophyllotoxin analogues; etoposide, teniposide and NK 611 using human lung cancer cell lines].

In an attempt to predict the antitumor activity of a new podophyllotoxin analogue, NK 611, in the treatment of lung cancer, we compared the drug with etoposide and teniposide using four human small cell lung cancer (SCLC) cell lines, SBC-2, -3, -4, -7, and two non-small cell lung cancer cell lines, ABC-1, EBC-1. In terms of the fifty percent tumor growth inhibitory concentration (IC 50) determined by MTT assay, teniposide was most potent among the drugs. The degree of cross-resistance of each drug was investigated using an etoposide-resistant SCLC subline (SBC-3/ETP), an adriamycin-resistant subline (SBC-3/ADM 100), and a cisplatin-resistant subline (SBC-3/CDDP). As for relative resistant (the ratio of IC 50 for resistant subline to that for the parent subline), NK 611 was least cross-resistant to etoposide, adriamycin, and cisplatin among drugs tested. These results indicate that NK 611 may play a role in a salvage chemotherapy for patients with resistant SCLC.

Bronchial atresia: report of a case and review of the literature.

We report herein an unusual presentation of bronchial atresia in a 28-year-old woman, in whom hyperlucency of the ventral segment, distal to a right extrahilar mass found on a routine chest X-ray, was not recognized. Atresia of the medial branch of the ventral segmental bronchus (B3b) with mucoid impaction in the dilated bronchus was finally disclosed by a right upper lobectomy. The patient had been asymptomatic, and physical examination demonstrated no abnormal findings such as decreased breathing sounds over the affected lung. Localized hyperlucency and a mass are the characteristic radiographic features of bronchial atresia. In the present case, however, hyperlucency distal to the mass, which was retrospectively evident on a computed tomogram of the chest, was not recognized. The preoperative diagnosis was also made difficult by the fact that the atresia was located on a subsequential branch (B3b) of the ventral segmental bronchus of the right upper lobe. Since computed tomography and magnetic resonance imaging are able to make an accurate diagnosis of bronchial atresia possible, surgery is often not indicated for asymptomatic patients. Moreover, although surgical intervention is required for patients with complications such as encroachment of normal pulmonary tissue or infection, resection should be as limited as possible to preserve normal lung tissue.

[Treatment of small cell lung cancer in the elderly: the progress and limitation of chemotherapy].

In order to assess the progress and limitation of chemotherapy in the treatment of small cell lung cancer in the elderly, we analyzed 218 patients who had entered into protocol studies between 1982 and 1990. Among those, there were 101 elderly patients (age of greater than or equal to 66 years) and 117 non-elderly patients (age of less than or equal to 65 years). Response to chemotherapy with or without chest irradiation was almost comparable for the elderly and the non-elderly; complete response rate was 52% for limited disease (LD) and 33% for extensive disease (ED) in the elderly, and it was 68% for LD and 23% for ED in the non-elderly. Survival figures of the two groups were quite similar: The median survival time was 12.6 months for the elderly and 14.5 months for the non-elderly, and the 3-year survival rate was 14% for both groups. An improvement of patient survival was observed along with the chronology of the protocols, i.e., with a escalation of dose intensity. Of interest, the improvement was rather evident in the elderly than in the non-elderly. Hematologic toxicity was considerable more frequent and severe in the elderly than in the non-elderly with non-significant statistics. The incidense of fever episodes while neutropenic was significantly more frequent in the elderly. Non-hematologic toxicity was almost comparable for the two groups, with a exception that the elderly showed a trend being predisposed to renal toxicity. In conclusion, such elderly patients as eligible for entry into a protocol study can benefit from intensive treatment as equally as non-elderly patients can.

[Double cancer in small cell lung cancer patients treated with intensive chemotherapy with or without radiation therapy].

Development of double cancer was evaluated in 311 small cell lung cancer patients who had received intensive chemotherapy with or without radiotherapy. Of those, 10 patients (3.2%) developed a second malignancy:stomach cancer in four, non-small cell lung cancer in three, acute myelogenous leukemia in two, and liver cancer in one. The cumulative risk for the development of double cancer was 1.0% at 1-year, 17.0% at 3-years, and 100% at 8.1 years. The relative risk for the development of double cancer calculated by person-year method utilizing age and sex adjusted cancer incidence in Japan was 2.96-fold (p less than 0.01). The risk of non-small cell lung cancer (6.65-fold) and acute myelogenous leukemia (54.9-fold) was particularly high. Of 21 patients who survived disease-free for more than 2 years, 8 patients died; four patients (50%) died of second malignancy, two died of infectious disease, and only two patients died from recurrent small cell lung cancer. These results indicate that a cautious follow-up program for the detection of double cancer is indicated in patients surviving small cell lung cancer.

Phase II study of ifosfamide, cisplatin, and vindesine combination in advanced non-small cell lung cancer.

Twenty-seven previously untreated patients with unresectable non-small cell lung cancer were treated with a 3-drug combination of ifosfamide, cisplatin, and vindesine as a phase II study. Patients received ifosfamide, 1.3g/m2, on days 1 to 5; cisplatin, 20mg/m2, on days 1 to 5; and vindesine, 3mg/m2, on days 1 and 8; with a sufficient parenteral hydration. Courses were repeated every 4 weeks. Twenty males and seven females with a median age of 61 years were treated and fully evaluated. Five patients had stage IIIA, seven had stage IIIB, and 15 had stage IV disease. One patient with adenocarcinoma achieved a complete response and 16 achieved a partial response, for an overall response rate of 63% (95% confidence limit: 45% to 81%). The median duration of response was 34 weeks (range: 9 to 52 weeks). The median survival time was 58 weeks for patients with IIIA/B disease, and 33 weeks for those with IV disease. The major toxicity was myelosuppression, however, it was generally well-tolerated. These results indicate that the 3-drug combination is active against non-small cell lung cancer and warrants further clinical trials.

[A statistical analysis of serum sialyl Lewis X-1 (SLX), CEA, SCC and NSE levels in patients with lung cancer].

Serum SLX, CEA, SCC and NSE levels were serially measured in 266 patients with lung cancer and compared with those in 345 patients with benign respiratory disorders (BRD). The positive rate for CEA in lung cancer (44.4%) and the false-positive rate in BRD (15.3%) were the highest among the 4 markers. The positive rate for SLX in lung cancer (32.0%) was lower than that of CEA, while the false-positive rate for SLX in BRD (7.2%) was lower than that of CEA. The positive rate for SLX was highest in adenocarcinoma and correlated better with the clinical stages than did CEA. SCC and NSE were specifically elevated in squamous cell carcinoma and small cell carcinoma, respectively. Using these 4 markers, only 70.2% of patients were correctly diagnosed as having lung cancer or BRD. In monitoring treatment effect, only SLX showed a statistically significant correlation with regression and progression in adenocarcinoma, while NSE and SLX showed such a correlation in small cell carcinoma. Serum tumor markers seem to be less sensitive for the diagnosis of lung cancer than chest X-ray and sputum cytology, indicating that a search for more specific markers is still required. However, in monitoring treatment effect, SLX appeared to be suitable for adenocarcinoma, while NSE and SLX seemed to be useful in small cell carcinoma.

[Patterns of relapse in patients with small cell lung cancer--the effect of chest irradiation and prophylactic cranial irradiation combined with intensive chemotherapy on long-term survival].

The pattern of relapse was analyzed in patients with small cell lung cancer (SCLC). Of 180 patients treated with intensive combination chemotherapy between 1976 and 1987, 75 achieved complete response (CR). Of 47 patients with limited disease (LD), 20 (43%) initially relapsed in the chest and 7 (15%) in the brain. Among 27 patients with extensive disease (ED), the chest was also the most frequent site of relapse (44%) followed by the brain (19%). In LD patients who had received chemotherapy plus chest irradiation, the initial relapse rate and the cumulative relapse rate in the chest at 2 years were only 29% and 35.4%, respectively. These rates were significantly lower compared with the rates of 69% and 76.5% for patients who had received chemotherapy alone (p less than 0.05). Survival was improved to some extent by the addition of chest irradiation, but not significantly, however, the long-term survival rate favored those receiving chest irradiation. Prophylactic cranial irradiation (PCI) reduced the frequency of brain relapse and significantly improved the survival of SCLC patients achieving CR. The median survival time and 5-year survival rate of patients who received PCI were 23.1 months and 26.7%, which these figures were only 14.0 months and 8.3% for those who had not respectively. Analysis using Cox's proportional hazard model showed that PCI was the greatest prognostic factor favoring the SCLC patients achieving CR. These results indicate that chest irradiation and PCI in conjunction with intensive combination chemotherapy are effective for cases of SCLC with CR.

[Small cell lung cancer; a retrospective analysis of results of chemotherapy and chemo-radiotherapy].

In order to assess the development of treatments and the curability of small cell lung cancer, we analysed a total of 239 patients entered in our protocol study since 1976. Median survival time was 68 weeks for 127 patients with limited disease and 48 weeks for 112 with extensive disease. Three-year survival rate was 18% for those with limited disease, whereas it was only 5% for extensive disease. The median survival time and long-term disease-free survival rate has been improved with an introduction of aggressive chemotherapy including new drugs such as etoposide and cisplatin. Chest irradiation in addition to intensive chemotherapy played a substantial, but not significant, role for prolonging patient survival in those with limited disease. Nevertheless, the pace of therapeutic advances has been slowed and appears to reach a plateau. In this paper, the authors try to find some obstacles in the treatment of the disease, and to indicate some strategies to gain a progress.