Development of inverted pendulum thrust stand with spring-shaped wire for high power electric thrusters.

Pendulum thrust stands are used to measure the thrust of electric propulsion systems for spacecraft. A thruster is mounted on a pendulum and operated, and the pendulum displacement due to thrust is measured. In this type of measurement, the pendulum is also affected by nonlinear tensions due to wiring and piping that deteriorate the accuracy of the measurement. This influence cannot be ignored in high power electric propulsion systems because complicated piping and thick wirings are required. Therefore, to reduce the influence of tension due to wires and tubes, we developed an inverted pendulum-type thrust stand with pipes and wirings as springs. In this paper, we first derive the design guidelines for spring-shaped wires; the necessary conditions for sensitivity, responsivity, spring shape, and electric wire were formulated. Next, a thrust stand was designed and fabricated based on these guidelines, and the performance of the stand was evaluated through calibration and thrust measurements using a 1 kW-class magneto-plasma-dynamics thruster. The sensitivity of the thrust stand was 17 mN/V, the normalized standard deviation of the variation of the measured values owing to the structure of the thrust stand was 1.8 × 10-3, and the thermal drift during the long-time operation was ∼4.5 × 10-3 mN/s.

Key factors for the dynamic ETEM observation of single atoms.

We present further modifications to aberration-corrected environmental transmission electron microscopy (AC-ETEM) for the dynamic HRTEM observation of single atoms. Additional pumping levels that include three additional turbomolecular pumps (TMPs) enable a base pressure of 3.5 × 10(-5) Pa in the sample chamber. The effect of these additional TMPs on image resolution was measured in reciprocal space using information limit (Young's fringes) on a standard cross grating sample and also with platinum (Pt) single atoms on an amorphous carbon film (Pt/a-carbon). The Pt/a-carbon was used for measuring the effect of gas pressure on single-atom imaging in addition to the evaluation of vibrations of TMPs, samples, magnetic lenses and a microscope column of the AC-ETEM. TMPs did not affect the ETEM imaging performance when an anti-vibration table was used, and 0.10-nm resolution was achieved. Dynamic ETEM observation of Pt single atoms was achieved in 4.0 × 10(-2) Pa of air, using a modified AC-ETEM system and a high-speed CCD camera with a time resolution of 0.05 s.

Vitrification and transfer of cynomolgus monkey (Macaca fascicularis) embryos fertilized by intracytoplasmic sperm injection.

Protocols for cryopreservation of monkey embryos are not well established. The objective of the current study was to determine the efficacy of the polypropylene strip method for cryopreserving cynomolgus monkey embryos. Cynomolgus monkey embryos, 63 and 56 at the 4- to 8-cell and 56 blastocyst stages, respectively, were produced by intracytoplasmic sperm injection and in vitro culture, and vitrified using a polypropylene strip. For these two stages, 95 and 86% survived after thawing and pregnancy rates were 29.2% (7 pregnant females/24 recipients, with three live births) and 0% (n = 16 recipients). These were apparently the first live births obtained from embryos fertilized by ICSI. In conclusion, 4- to 8-cell preimplantation cynomolgus monkey embryos were successfully cryopreserved using a polypropylene strip.

[Analysis of the action of dextran sulfate as a prophylaxis for peritoneal cancer metastasis, and its acting mechanism].

Although peritoneal cancer metastasis has the highest frequency of postoperative recurrence among digestive organ malignant tumors, there is no still decisive treatment. Dextran sulfate (DS) as a prophylaxis for cancer metastasis was examined with respect to its effect on cultured cells. DS was made to act on a strong adhesive neoplasm cell, and the action and acting mechanism were examined with respect to 1. readhesiveness, 2. cell cycle, and 3. gene analysis. The results suggest that: i) Once tumor cells are detached by DS, the free cells do not attach even when DS is removed, and ii) DS causes the cells to stop in the G1/G0 phase.

Combined use of electrosurgical incisions and balloon dilatation for the treatment of refractory postoperative pyloric stenosis.

BACKGROUND: Drug therapy plus balloon dilatation without gastroscopic incision does not always relieve postoperative pyloric stenosis. METHODS: Five patients with postoperative pyloric stenosis whose symptoms did not improve with drug therapy and balloon dilatation underwent a combination of gastroscopic incision and balloon dilatation. Two or 3 small radial incisions were made in the stenotic muscle of the pylorus electrosurgically at gastroscopy. Then the stenotic muscle layer was loosened and split bluntly along the incisions with balloon dilatation for 15 to 20 minutes. One week later, the combination procedure or balloon dilatation alone was repeated to prevent restenosis. RESULTS: In the 5 patients, the stenosis was improved with the combination therapy. No complications were observed. CONCLUSIONS: Combined use of gastroscopic incision and balloon dilatation may be considered for patients with refractory pyloric stenosis caused by surgical truncal vagotomy.

Local injection of anti-cancer drugs bound to carbon particles for early gastric cancer--a pilot study.

BACKGROUND/AIMS: A new dosage formulation consisting of an anti-cancer drug bound to activated carbon particles was developed for a local injection against early gastric cancer so that the dosage formulation yields chemotherapeutic effects selectively to the lymph node metastases as well as to the primary lesion. METHODOLOGY: As a pilot study, the new dosage formulation, total of 50-200 mg of methotrexate only or total of 200 mg of methotrexate plus 8 mg of mitomycin C, was injected into the primary lesions and the adjacent gastric wall of 8 patients with early gastric cancer, guided by a gastrofiberscope before gastrectomy. The surgically resected specimens were examined histologically for the therapeutic effects on the primary lesion and its nodal metastasis. RESULTS: The therapeutic effects were seen in 2 of 4 lymph node metastases (50%) and 5 of 8 of the primary lesions (63%), as confirmed histologically with degeneration and/or necrosis. CONCLUSIONS: Preoperative local injection of the new dosage formulation will be useful to give chemotherapeutic effects on the potential metastases in the regional nodes as well as to the primary lesion.

Dextran sulfate inhibits injured abdominal wall-specific tumor implantation in mice.

Tumor recurrence is often seen at sites where the peritoneum has been injured during surgery for gastrointestinal malignancies. It is thought that malignant cells released from the tumor during surgery implant in the sites of injury in the abdominal wall and cause tumor recurrence. Here we use dextran sulfate (DS) as an antagonist to cell adhesion for preventing implantation of i.p. seeded malignant cells, thus suppressing the recurrent tumor formation often observed at the site of injury in postoperative abdominal walls. DS was tested for anti-adherent activity against B-16 melanoma cells to injured abdominal wall specimens ex vivo and showed the capacity to significantly impair B-16 melanoma cell adherence compared to controls without DS. DS was also tested for the activity to prevent i.p. seeded B-16 melanoma cells from implanting in the site of injury in the abdominal wall in vivo and DS prevented B-16 melanoma cells from implanting in the sites of injury in the abdominal wall. In the test for the activity to improve survival in mice after B-16 melanoma was inoculated i.p., DS improved the survival of mice as compared to the controls without DS. We conclude that DS may be useful in preventing surgically promoting tumor implantation at sites of injury in post-operative abdominal wall treated for gastrointestinal malignancies.

Extensive gastrectomy and carbon-adsorbed mitomycin C for gastric cancer with peritoneal metastases. Case reports of survivors and their implications.

BACKGROUND/AIMS: Extensive gastrectomy, defined as gastrectomy with complete omentectomy and extended lymphadenectomy, improves the survival of gastric cancer patients with peritoneal metastases, even though peritoneal metastasis is considered the end-stage of cancer. MMC-CH, a new dosage formulation of mitomycin C, extended the survival of rabbits with peritoneal carcinomatosis as compared to aqueous mitomycin C. METHODOLOGY: We retrospectively reviewed 114 patients who underwent gastrectomy for gastric cancer with peritoneal metastases. RESULTS: Six patients survived for more than 5 years after the therapy out of 63 patients treated with MMC-CH therapy and extensive gastrectomy for gastric cancer with P1, i.e., metastases to the adjacent peritoneum but no metastasis to the distant peritoneum, or P2, i.e., a few metastases to the distant peritoneum. However, there were no 5-year survivors in patients with P3, i.e., numerous metastases to the distant peritoneum, or in patients treated with incomplete omentectomy, limited lymphadenectomy and no MMC-CH therapy. CONCLUSIONS: The results imply that gastric cancer patients with P1 or P2 have a possible chance to survive more than 5 years when treated with MMC-CH therapy and extensive gastrectomy.

Effect of extensive lymph node dissection on the survival of early gastric cancer.

BACKGROUND/AIMS: A retrospective analysis of 628 cases of early gastric cancer was performed to evaluate prognostic significance of extensive lymph node dissection. METHODOLOGY: The patients were assigned to either D0/D1 (n=177) group or D2/D3 group (n=451) according to the extent of lymph node dissection and the survival of the two groups was compared. RESULTS: The survival rate of D2/D3 group was significantly higher than D0/D1 group in the case of both including and excluding unrelated cause of death (p<0.0001 and p<0.005, respectively). CONCLUSIONS: Though early gastric cancer is excellent prognostic disease, very few numbers of patients with recurrence really remain. Our data show extensive lymph node dissection was effective to prolong the survival of patients with early gastric cancer.

Endoscopic incision and balloon dilatation for cicatricial anastomotic strictures.

BACKGROUND/AIMS: Endoscopic incision or balloon dilatation is common therapy for cicatricial anastomotic strictures after gastrointestinal surgery. These therapies are not always effective. METHODOLOGY: There were 6 patients who failed either endoscopic incision or balloon dilatation alone and who underwent a combination of the two therapies. Two or three small radial incisions were made in the scar of the stricture with the endoscopic electrocautery under direct vision with fiberscopy. Then, the incisions were split bluntly and the stenosis was dilated over 15-20 minutes with balloon-dilator. This procedure was performed once or twice at a 2-week interval. RESULTS: In 5 of the 6 patients, the stenosis was improved in subjective criteria and objective symptoms. In the last patient, only objective improvement was noted. There were no complications. CONCLUSIONS: Endoscopic incision plus balloon dilatation is an effective and safe treatment for cicatricial anastomotic strictures which have failed either therapy alone.

Complete omentectomy and extensive lymphadenectomy with gastrectomy improves the survival of gastric cancer patients with metastases in the adjacent peritoneum.

BACKGROUND/AIMS: The omentum is the site where peritoneal metastases occur most frequently. It has not been shown whether complete resection of the omenta during gastrectomy improves the survival of gastric cancer patients with macroscopic peritoneal metastases. METHODOLOGY: We retrospectively analyzed 126 patients who underwent gastrectomies for gastric cancer with peritoneal metastases but without hematogenous metastases. The 126 patients were stratified according to their grade of peritoneal metastases into three groups: the P1 patients (patients with peritoneal metastases in the adjacent peritoneum but not in the distant peritoneum); the P2 patients (patients with a few peritoneal metastases in the distant peritoneum); and the P3 patients (patients with many metastases in the distant peritoneum). In each group, the survival and clinicopathological characteristics were compared between patients treated by complete resection of the greater omentum and the lesser omentum plus extensive lymphadenectomy during gastrectomy, versus patients treated by incomplete resection of the omenta and non-extensive lymphadenectomy during gastrectomy. RESULTS: Complete omentectomy and extensive lymphadenectomy during gastrectomy improved survival significantly only in the P1 patients. Other clinicopathological characteristics did not differ between them. CONCLUSION: Complete omentectomy and extensive lymphadenectomy is recommended in patients with peritoneal metastases in the adjacent peritoneum but not in the distant peritoneum.

Therapeutic effects of 5-fluorouracil microspheres on peritoneal carcinomatosis induced by Colon 26 or B-16 melanoma in mice.

The delivery formulation 5-FU-MS [5-fluorouracil (5-FU) incorporated in microspheres composed of a poly(glycolide-co-lactide) matrix] slowly releases 5-FU over 3 weeks. 5-FU-MS delivers higher concentrations of the drug to the i.p. tissues for a longer period of time with lower blood plasma concentrations than does an aqueous 5-FU solution and reduces toxicity. In this study, we evaluated the therapeutic effects of 5-FU-MS on peritoneal carcinomatosis in mice. Four days after an i.p. inoculation with Colon 26 or B-16 PC melanoma, 5-FU at 200 mg/kg was administered i.p. as 5-FU-MS or as an aqueous solution of 5-FU. 5-FU-MS extended the survival of mice bearing Colon 26 or B-16 PC melanoma significantly better than the equivalent dose of aqueous 5-FU solution.

Prevention of peritoneal metastasis of cancer with dextran sulfate--an experimental study in mice.

Peritoneal metastases occur most often in the greater omentum, where tumor implantation sites are densely distributed. We used dextran sulfate (S-Dex) as an anti-cell-adherence agent to prevent i.p. seeded malignant cells from causing peritoneal metastases. S-Dex was tested for its anti-adherent activity against B-16 melanoma cells on plastic, and was examined for its ability to prevent implantation in the omentum and to improve survival in mice after B-16 melanoma was inoculated i.p. S-Dex prevented B-16 melanoma cells from adhering to the plastic wall. S-Dex reduced the number of B-16 melanoma cells implanted into the greater omentum and improved the survival of mice inoculated with B-16 melanoma cells. We conclude that S-Dex attenuated peritoneal metastases when B-16 melanoma cells were seeded i.p.

[Endoscopic local injection of anticancer drugs bound to carbon particles for treatment of upper digestive tract cancers--clinical trials].

A new dosage formulation consisting of anticancer drugs bound to carbon particles was developed for treating cancers of the upper digestive tract, and is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site, as compared to a drug in aqueous solution form. Thirteen patients with histologically proven carcinoma (8 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), in whom surgical treatment was contraindicated, received intra- and peritumoral injection of the new dosage formulation (total dose of 35-100 mg of peplomycin or 250-500 mg of methotrexate) guided by esophago- or gastro-fiberscope. Eleven of these 13 patients are currently alive, 12-64 months after therapy, or they died without evidence of recurrence 12-98 months after the treatment. One patient has remained cancer-free for 37 months after a second course of the therapy given to treat a recurrence found 26 months after the first treatment. Another patient has a recurrent tumor 9 months after the therapy and is now going to undergo a second course of treatment. Side effects were not severe and well-tolerable.

[Visualising lymph nodes by aclarubicin bound to activated carbon particles in breast cancer surgery].

A new dosage formulation (ACR-CH), composed of aclarubicin (ACR) bound to fine activated carbon particles, has been developed for the treatment of lymph node metastases in breast cancer. ACR-CH is designed to (a) adsorb a great amount of aclarubicin and desorb in a free state; (b) distribute a greater amount of ACR for a longer period of time selectively to the regional lymph nodes; (c) be decreased in the systemic toxicity; and (d) enhance its therapeutic effect on lymph node metastases. In this clinical trial in 20 patients with breast cancer, ACR-CH was injected intra- and peritumorally just before operation for breast cancer, and we examined the extent of blackened nodes produced by ACR-CH. ACR-CH blackened about 70% of the axillary lymph nodes with cancer metastasis as well as the nodes without metastasis. In conclusion, ACR-CH will be useful for dissection of lymph nodes by visualizing the nodes during operation for breast cancer.

Selective drug delivery to peri-tumoral region and regional lymphatics by local injection of aclarubicin adsorbed on activated carbon particles in patients with breast cancer--a pilot study.

ACR-CH, which consists of aclarubicin (ACR) adsorbed onto activated carbon particles, was developed for locoregional chemotherapy for breast cancer. Thirty patients with breast cancer received an ACR (10 mg) injection intra- and peri-tumorally, either as ACR-CH or as ACR aqueous solution (ACR-AQ) 5 min before the operation for breast cancer. The ACR concentrations were significantly higher in the peritumoral regions and regional lymph nodes, and were also significantly lower in the blood plasma in patients given ACR-CH versus patients given ACR-AQ.

Endoscopic local injection of a new drug delivery formulation, anticancer drug bound to carbon particles, for digestive cancers: pilot study.

A new dosage formulation consisting of an anticancer drug bound to activated carbon particles was developed for the treatment of digestive cancer in patients in whom operation is contraindicated. The new formulation is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site compared to distribution of the drug in aqueous solution. In 12 patients with histologically proven carcinoma (7 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), an anticancer drug bound to carbon particles (total dose, 40-100 mg peplomycin or 250-500 mg methotrexate per person) was injected endoscopically into the primary lesions. Eleven of the 12 patients are currently alive, 12-64 months after therapy, or they died without evidence of cancer 12-98 months after the treatment. One patient has remained cancer-free for 32 months after a second course of the new formulation therapy given to treat a recurrence detected 26 months after the first treatment. Endoscopic injection of this new dosage formulation seems to control these digestive cancers in patients in whom operation is contraindicated.

Selective delivery of 5-fluorouracil (5-FU) to i.p. tissues using 5-FU microspheres in rats.

A new formulation has been developed for the delivery of 5-fluorouracil (5-FU) in treating peritoneal carcinomatosis. The new formulation (5-FU-MS) involves the incorporation of 5-FU into microspheres composed of a poly(glycolide-co-lactide) matrix. The incorporated 5-FU is released slowly over a 3 week period. We investigated the drug distribution and pharmacokinetics of 5-FU in rats receiving an i.p. injection of 5-FU-MS or aqueous 5-FU solution. The concentration of 5-FU was higher in the i.p. tissues (omentum and mesentery) and lower in the extraperitoneal tissues (blood plasma, lung and heart) in rats given 5-FU-MS than in rats given the aqueous 5-FU solution. Pharmacokinetic analysis showed that the area under the curve (AUC) was significantly greater in the omentum and the mesentery than in other tissues of rats given 5-FU-MS. There was no significant difference in the AUC in the tissues of rats given the aqueous 5-FU solution.

[Therapy of carcinomatous peritonitis by the angiogenesis inhibitor TNP-470 in mice: analysis of timing and doses for intraperitoneal administration].

In order to perform therapy for carcinomatous peritonitis by a new angiogenesis inhibitor, TNP-470, we investigated the effective timing and the optimal doses for intraperitoneal administration using two mice models. In both carcinomatous peritonitis models caused by M 5076 tumor and B 16 melanoma, the early administration of TNP-470 within one week after tumor inoculation extended the survival times of the mice receiving the drugs, whereas the administration of TNP-470 one week or later after inoculation did not affect the survival time. However, there were significant differences in the effective therapeutic doses of TNP-470 between the two models. It is important to select the best timing and doses for intraperitoneal administration of TNP-470 based on the state of angiogenesis and the sensitivity of the tumor tissues to TNP-470.

[Endoscopic injection of methotrexate bound to activated carbon particles in the treatment of gastric cancer].

A new dosage formulation (MTX-CH), composed of fine activated carbon particles absorbing methotrexate (MTX), distributes concentrated MTX for long periods of time to the regional lymph nodes as well as to the injection site, in animal experiments. MTX-CH would enhance the therapeutic effects not only on the primary lesion but also on the lymphatic metastasis. As clinical trials, (A) in five patients with early gastric cancer, MTX-CH at 50 to 200 mg/person of MTX was injected endoscopically in and around the primary lesion before operation. Surgically removed specimens showed that three out of the 5 primary lesions had disappeared or were necrotic, and the remaining two lesions had shrunk. (B) Three patients with contraindication to surgery received the endoscopic injection of MTX-CH. The MTX-CH injected at 250 to 1,500 mg/person into and around the primary lesion of relatively early gastric cancer resulted in the complete disappearance of the primary lesions for 14 to 24 months up to the present time without enlargement of the lymph nodes. It was thought that local injection of MTX-CH will be effective therapy, especially for gastric cancer with potential lymphatic metastasis in patients with contraindications to surgery.