Cavity-Enhanced 2D Material Quantum Emitters Deterministically Integrated with Silicon Nitride Microresonators.

Optically active defects in 2D materials, such as hexagonal boron nitride (hBN) and transition-metal dichalcogenides (TMDs), are an attractive class of single-photon emitters with high brightness, operation up to room temperature, site-specific engineering of emitter arrays with strain and irradiation techniques, and tunability with external electric fields. In this work, we demonstrate a novel approach to precisely align and embed hBN and TMDs within background-free silicon nitride microring resonators. Through the Purcell effect, high-purity hBN emitters exhibit a cavity-enhanced spectral coupling efficiency of up to 46% at room temperature, exceeding the theoretical limit (up to 40%) for cavity-free waveguide-emitter coupling and demonstrating nearly a 1 order of magnitude improvement over previous work. The devices are fabricated with a CMOS-compatible process and exhibit no degradation of the 2D material optical properties, robustness to thermal annealing, and 100 nm positioning accuracy of quantum emitters within single-mode waveguides, opening a path for scalable quantum photonic chips with on-demand single-photon sources.

EXAFS study of phase transitions in KIO3.

The iodine K-edge EXAFS study of KIO3 was performed to clarify local structural changes on the successive phase transitions. The pair-distribution function of three oxygen atoms in an oxygen octahedron is almost independent on temperature like a covalent bond, whereas that of the other three is gradually reduced with increasing temperature like an ionic bond. The result indicates that iodine and oxygen atoms exist as an IO3- molecule in a pseudo-perovskite-type structure. The anomalous behavior in the Debye-Waller factor for the latter pair-distribution function appears around 50 K, which is associated with the orientational glass transition.

Effect of human urinary macrophage colony-stimulating factor on the immune functions and the blood cell counts in patients with ovarian carcinoma receiving cytotoxic chemotherapy.

The present study investigated the effect of macrophage colony-stimulating factor (M-CSF) on the immune functions and blood cell counts of patients with ovarian carcinoma receiving cytotoxic chemotherapy (CTX). Seventy-five consecutive patients with white blood cell counts less than 3,000/microl after CTX were randomly assigned to receive either M-CSF (human urinary macrophage colony-stimulating factor: hM-CSF, 8x106 U as 7-day intravenous infusions) or no treatment. Immune assays in addition to routine peripheral blood examinations were performed on these patients at various time points. hM-CSF dosing significantly increased monocyte, lymphocyte, granulocyte, and platelet counts that were decreased by CTX. hM-CSF also significantly enhanced lymphokine-activated killer and natural killer activities, which was accompanied by a significantly augmented interleukin (IL)-2 production. Interestingly, IL-2 production was enhanced by hM-CSF dosing in 24 of the 27 patients with a pre-hM-CSF level of IL-2 below 10 U/ml, but such an effect was not observed in nine of the 10 patients having a basal value of 10 U/ml or higher. Thus, hM-CSF is considered to be a cytokine that can augment or regulate immune functions impaired by CTX and increase blood cell counts that are decreased by CTX.

Hyperkalemia probably reverses the antiarrhythmic effects of amiodarone: a case report.

Sustained monomorphic ventricular tachycardia (VT) developed in a 58-year-old man with acute myocardial infarction and end-stage renal disease. Amiodarone was effective in preventing VT recurrence. Sustained VT was not induced during an electrophysiologic study. However, VT recurred during accidental hyperkalemia, which was caused by the change of dialysis therapy from peritoneal dialysis to hemodialysis. VT subsided with correction of hyperkalemia. Thereafter, VT did not recur as long as the serum potassium concentration was kept within the normal range. Several months later, the patient died suddenly because poor dietary compliance resulted in an increase in his potassium concentration. This case suggests that hyperkalemia may reverse the potent antiarrhythmic effects of amiodarone.

Combination of consecutive low-dose cisplatin with bleomycin, vincristine, and mitomycin for recurrent cervical carcinoma.

PURPOSE: To evaluate the efficacy and toxicity of combination chemotherapy with bleomycin, vincristine, mitomycin, and consecutive low-dose (CLD) administration of cisplatin (CLD-BOMP) for patients with recurrent cervical carcinoma. PATIENTS AND METHODS: Ninety patients with recurrent cervical carcinoma and no prior chemotherapy were enrolled onto this study. The median age was 56 years. Eighty-seven of the 90 patients had received prior radiotherapy. The CLD-BOMP regimen was bleomycin 5 mg infused continuously days 1 through 7; vincristine 0.7 mg/m2 bolus day 7; mitomycin 7 mg/m2 bolus day 7; and cisplatin 10 mg/m2 infused over 4 hours days 1 through 7. The treatment was repeated at 3-week intervals. RESULTS: All 90 patients were assessable for response, toxicity, and survival. After a median of four cycles (range, two to 10 cycles), we observed objective responses in 68 patients (76%), with 25 (28%) complete responses (CRs) and 43 (48%) partial responses (PRs; 95% confidence interval (CI), 66 to 85; 18 to 38; 37 to 59, respectively). Median survival for all 90 patients was 24.3 months (range, 2.3 to 100 months). The median survival for patients who achieved CR, PR, no change (NC), and progressive disease (PD) were not reached (NR), 23.6, 8.2, and 6.4 months, respectively. The median progression-free survival for patients who achieved CR and PR were NR and 12.3 months, respectively. There was no significant nausea or vomiting, nephrotoxicity, or pulmonary toxicity, which was attributable to the CLD-cisplatin and the adequate dosing schedule of bleomycin. The reduced toxicities allowed this regimen to be administered at the projected dose-intensities. CONCLUSION: The CLD-BOMP regimen has significant antitumor activity with markedly reduced toxicity.

Cytotoxic agents active against mucinous adenocarcinoma of the ovary.

The purpose of the present study was to evaluate cytotoxic agents active for mucinous adenocarcinoma of the ovary (MACO) which is considered to be intrinsically platinum-resistant. We first conducted in vitro chemosensitivity tests assessing cytotoxic activities of various anti-cancer agents against MACO using a cell line, designated OMC-3, established from ascites of a patient with histologically pure MACO. The most active single agent was SN-38 (active substance of CPT-11 in vivo). The second most potent agent was mitomycin-C (MMC) followed by doxorubicin (DOX). In vivo chemo-sensitivity test of agents on OMC-3 transplanted into Balb/c nude mice demonstrated that MMC was most potent, followed by DOX. Moreover, a combination of CPT-11 and MMC exhibited the highest anti-tumor activity in this animal model. Cisplatin was found to be ineffective in both the in vitro and in vivo experimental system. Clinical trial with a combination of MMC and CPT-11 are justified in patients with MACO.

A phase II study of combined CPT-11 and mitomycin-C in platinum refractory clear cell and mucinous ovarian carcinoma.

This article reviews the preliminary but encouraging clinical data obtained from patients with platinum-refractory clear cell or mucinous carcinoma of the ovary who were treated with a chemotherapy regimen including irinotecan hydrochloride (CPT-11). Twenty-five patients with platinum-refractory macroscopic disease of which histologic type was either clear cell or mucinous carcinoma were treated. CPT-11 was administered at a dose of 120 mg/m2 intravenously (i.v.) over 4 hours on days 1 and 15, and mitomycin-C (MMC) was given IV as a bolus at a dose of 7 mg/m2 on days 1 and 15. At least 2 cycles of this regimen, 4 weeks apart, were given to the 25 patients. After a median of 4 cycles (range 2 to 8), we observed objective responses in 13 patients (52%), with 5 complete responses (CRs; 20%) and 8 (32%) partial responses (PRs) (95% confidence interval, 32.4% to 71.6%, 4.3% to 35.7%, 13.7% to 50.3%, respectively). The median overall survival time for all 25 patients was 15.3 months (range 3.5 to 38.0). Median overall survival time of the responders was 33.7 months versus 6.1 months of the non-responders (Log-rank, P = 0.0003). The median progression-free survival times for patients obtaining CR, PR, and CR+PR were 31.8 months (range 12.9 to 34.4), 10.5 months (range 5.6 to 18.2), and 12.9 months (range 5.6 to 34.4), respectively. Toxic effects were acceptable and included manageable haematologic reactions, diarrhoea, nausea/vomiting, and alopecia.

Longitudinal dissociation in the his bundle: a possible mechanism of two distinct cycle lengths in atrioventricular reentrant tachycardia.

Two wide QRS tachycardias with identical morphology but different cycle lengths (CLs) developed in a 63-year-old man. Electrophysiological study demonstrated inducible atrioventricular reentrant tachycardia (AVRT) due to a concealed left posterior accessory pathway (AP), which was successfully ablated by radiofrequency application. Neither dual AV nodal pathways nor other APs were documented. Splitting of the His-bundle electrogram was shown, and programmed stimulation induced sudden prolongation of intra-hisian conduction time. These results suggest longitudinal dissociation in the His bundle may be responsible for two distinct CLs in AVRT without dual AV nodal physiology.

Activity of cytotoxic agents against clear cell carcinoma of the ovary which is intrinsically platinum-refractory.

The aim of the present study was to evaluate cytotoxic agents active for clear cell carcinoma of the ovary (OCCA) which is intrinsically platinum-resistant. We first conducted in vitro chemosensitivity tests assessing antitumor activities of Various agents against OCCA using two cell lines (HAC-2 and KK) established from ascites of patients with pure OCCA. The most potent single agent was SN-38 (active substance of CPT-11 in vivo) in both cell lines. The second most potent agent was mitomycin-C (MMC) followed by doxorubicin (DOX) in HAC-2 and DOX followed by MMC in KK, respectively. In vivo chemosensitivity test of agents on HAC-2 transplanted into BALB/C nude mice demonstrated that MMC was most potent, followed by DOX and CPT-11. Moreover, a combination of CPT-11 and MMC exhibited the highest anti-tumor activity in this animal model. Cisplatin, etoposide, and paclitaxel were found to be ineffective in either the in vitro or in vivo experimental system. Clinical trial with a combination of MMC and CPT-11 are warranted in patients with OCCA.

[Effects of nicorandil on coronary collateral circulation depend on the donor arteries].

The effects of nicorandil on coronary collateral circulation during exercise-induced ischemia were compared between the different donor arteries in 13 patients with effort angina, 7 with complete obstruction of the left anterior descending artery (LAD) with well-developed collateral vessels from the right coronary artery (RCA) (LAD group), and 6 with complete occlusion of the RCA (segment 2-3) with well-developed collateral vessels from the LAD (RCA group). Initial percentage thallium (%TI) uptake (thallium-201 single photon emission computed tomography) and washout rate were measured in the anterior, septal and posterior regions during ergometer exercise. The submaximal treadmill exercise test was also performed using a cardiopulmonary monitoring system to measure Vo2 at anaerobic threshold (AT). After the controls were obtained, nicorandil (15 mg/day) was administered for 4 weeks, during which ergometer exercise and treadmill exercise tests were carried out repeatedly. A significant improvement of initial %TI uptake on exercise was observed in the LAD group with nicorandil therapy, but no improvement was shown in the RCA group. The AT significantly increased after nicorandil treatment in the LAD group (13.9 +/- 0.38-->16.8 +/- 1.18 ml/min/kg), reflecting the improvement of cardiac function through the increased collateral flow. However, in the RCA group, it remained unchanged, suggesting no improvement of cardiac function. Nicorandil was effective to increase collateral flow from the RCA, but ineffective on that from the LAD. Nicorandil is an effective coronary dilator and is reported to affect both large and small coronary arteries. The effect on the collateral circulation is dependent on the donor artery supplying different areas. The vasodilator effect of nicorandil is mainly on the LAD, which is large enough to supply blood to a wider area of the heart, rather than the RCA.

Does appropriate endurance exercise training improve cardiac function in patients with prior myocardial infarction?

OBJECTIVE: The objective of the present study was to determine whether appropriate endurance exercise training improves cardiac function in patients with prior myocardial infarction. METHODS: Twenty-nine patients with prior myocardial infarction were divided into three groups (Group 1: control, Group 2: low-intensity training, Group 3: high-intensity training). Low and high training intensities were determined according to the gas exchange threshold of each patient. The patients in Groups 2 and 3 performed 15 min of home-based physical training safely, twice a day, 5 days a week for 2 months. Prior to and following this training, each patient performed two constant work rate tests (moderate and heavy intensity) and a symptom-limited incremental exercise test. RESULTS: Heart rates at rest and during exercise were decreased significantly after 2 months in all three groups. Stroke volume at rest increased significantly after 2 months only in Group 3. Stroke volume after 6 min of heavy-intensity exercise increased significantly in Groups 2 and 3. However, the ejection fraction at 6 min of heavy-intensity exercise increased significantly only in Group 3. The maximal work rate attained during incremental exercise testing increased significantly in Groups 2 and 3. This parameter did not significantly change in the control group. CONCLUSIONS: Effects of physical training on maximal exercise capacity were noted in both exercise training groups. However, improvement in cardiac function (such as stroke volume), both at rest and during exercise, was noted only in the high-intensity training group. Our results suggest that relatively high-intensity training may improve exercise capacity and cardiac function of patients with prior myocardial infarction.

[Report of nationwide questionnaire: intraperitoneal chemotherapy for advanced ovarian cancer based on clinical results--reports of 5th "Gynecologic Intraperitoneal Chemotherapy Study Group" meeting].

We established the "Gynecologic Intraperitoneal Chemotherapy Study Group" in October, 1990. To date 5 annual meetings have been held during the Japanese Cancer Therapy Meeting. The members decided to establish a standard protocol of intraperitoneal chemotherapy (IP-CTX) for advanced ovarian cancer based on the clinical results obtained at each institution. Thus we first collected the clinical data from the affiliated institutes. Questionnaires concerning the indication of IP-CTX and the resulting data were sent to physicians working at 267 facilities in January, 1994. As a result, the reply rate was 28.8% (77/267). According to the results from 40 institutions, the consensus was that patients with residuum less than 0.5 cm in diameter after primary debulking surgery were suitable for IP-CTX. However, the remaining 37 institutions reported that patients with a macroscopic residuum less than 2 cm in diameter or those with bulky residuum greater than 2 cm in diameter demonstrated good responses to IP-CTX. Thus, further analyses are required to elucidate the appropriate indication and establish the standard protocol of IP-CTX for ovarian cancer in a clinical setting.

[Successful treatment of clear cell adenocarcinoma of the ovary (OCCA) with a combination of CPT-11 and mitomycin C].

Among advanced ovarian cancer, OCCA has worse prognosis compared with serous cystadenocarcinoma because of its poor sensitivity to CDDP-based chemotherapy (CTX). Indeed, there has ever been no one patient with pure OCCA showing an appreciable response to CTX. OCCA has recently been increasing in prevalence and has occupied approximately 20-25% of all ovarian cancer. Thus, there is an urgent need to find effective regimens. Based on the results of chemosensitivity tests previously performed both in vitro and in vivo, we designed a combination of CPT (140 mg/m2, i.v.-infused over 4 hours on day 1, 15, and 29) and MMC (7 mg/m2, i.p. injection through a reservoir on day 1, 15, and 29). The course was repeated every 4 weeks. To date 10 pts were entered The median age was 53 (41-69). Among total 25 courses, grade 3 diarrhea was observed in 3 courses. Other toxic signs were acceptable. The responses by tumor size were 2 CR for disease < or = 2 cm in diameter, and 2 CR, 2 PR, 2 NC, and 2 PD for > 2 cm. Six responders showed a significantly longer survival compared with 4 non-responders (p < 0.0396 for Log-rank test). Thus, the present protocol is the first to demonstrate a significant activity for pure OCCA.

[Feasibility of peritoneal washing cytology through the totally implanted reservoir for early detection of peritoneal recurrence of ovarian cancer].

UNLABELLED: There have been no reliable ways to follow up ovarian cancer patients receiving optimal debulking. In this study, we assessed the feasibility of cytological diagnosis on peritoneal washing cells collected through a totally implanted reservoir as a tool in following up these patients. Between 1988 and 1993, 31 patients underwent optimal debulking and were implanted with a reservoir. After the operation, the patients were followed up at 2-4 week intervals with peritoneal washing cytology. Six patients were diagnosed as having a recurrence by the peritoneal washing cytology alone. And at this point there had been no other positive findings by other conventional methods. There were no complications caused by reservoirs. Activated mesothelial cells, multinucleated histiocytes and hemosiderine-laden histiocytes were characteristic cytologic findings accompanying adenocarcinoma cells. Hemosiderin-laden histiocytes were found by peritoneal washing cytology even before the appearance of adenocarcinoma cells. The appearance of hemosiderin-laden histiocytes may therefore be a sign of intraperitoneal recurrence of ovarian cancer. CONCLUSION: 1) Peritoneal washing cytology through a reservoir is useful for early detection of intraperitoneal recurrence of optimally debulked ovarian cancer without any significant complications. 2) The appearance of intraperitoneal hemosiderin-laden histiocytes may be sign of intraperitoneal recurrence of ovarian cancer.

[Endometrial carcinoma without myometrial invasion].

Between 1974 and 1991, 621 patients with endometrial cancer were treated with hysterectomy without any preoperative treatment. Subsequent pathological examinations revealed that 92 cases had no myometrial invasion. Clinicopathological analysis was carried out in the 92 patients. The results are as follows: 1. Complete surgery was carried out in all cases except one case with intraperitoneal dissemination. The relapse rate in the 91 cases was 2.2% (2/91). The 2 cases with recurrence had grade 1 (G1) and grade 2 (G2) adenocarcinoma and both cases manifested local recurrence. 2. Of 70 cases treated with pelvic lymphadenectomy, two cases (2.9%) with G1 adenocarcinoma exhibited a single node metastasis. The metastatic site was an external iliac lymph node in both cases. Despite the lymph node metastasis, the 2 cases have exhibited no relapse. 3. None of the 92 cases showed any evidence of adnexal metastasis. The positive rate of peritoneal cytology was 13.4% (9/67). Except for one case with peritoneal dissemination who also had positive peritoneal cytology, 8 cases with positive peritoneal cytology have not developed recurrence. This study showed that some endometrial cancer patients without myometrial invasion manifest recurrence, peritoneal dissemination or lymph node metastasis. It is therefore considered that lymphadenectomy and careful follow-up are necessary in every case of endometrial cancer, even in G1 cases without myometrial invasion.

[Clinical and pathological study of 24 patients with fallopian tube malignancy].

Clinical and pathological analyses were carried out in 24 patients with fallopian tube malignancy. The results are as follows: 1. Twenty-three patients had adenocarcinoma (well differentiated 11, moderately 6, poorly 6) and one patient had MMT (Müllerian mixed tumors). 2. There were 11 cases in stage I, 4 in stage II, 8 in stage III and 1 in stage IV according to Dodson's classification. 3. Atypical genital bleeding was the most common symptom, whereas 12.5% of patients had no symptoms. 4. Positive rates in cytology were 25.0% in cervico-vaginal smear and 55.0% in endometrial aspiration cytology. 5. The overall 5-year survival rate is 60.0%. The 5-year survival rates for stage I/II and stage III/IV were 88.9% and 16.7%, respectively. 6. The relapse rate of 16 patients treated with complete surgery was 25.0% (well differentiated 11.1%, moderately 0%, poorly 75.0%). Based on these observation, it is likely that patients with stage I/II have a good prognosis, however, patients with poorly differentiated adenocarcinoma have a high relapse rate, indicating that intensive adjuvant chemotherapy would be necessary in these cases. Cytologic examination, particularly endometrial aspiration cytology, is an effective method to use in detecting cases with fallopian tube malignancy early.

Occurrence of the antibody against human papillomavirus type 16 virion protein L2 in patients with cervical cancer and dysplasia.

Infection with HPV 16 is believed to be a major risk factor for cervical cancer. To correlate HPV 16 infection and carcinogenesis in the cervix, we examined by ELISA 326 sera from healthy females and patients with cervical cancer, cervical intraepithelial neoplasia, or dysplasia, for the presence of IgG antibodies against HPV 16 virion protein L2 expressed in Escherichia coli. Whereas 2 of 208 were positive in the healthy females, 4 of 23 and 6 of 90 were positive in the patients with cervical cancer and dysplasia, respectively. The findings indicate that infection with HPV 16 is related to cancer and dysplasia of the cervix. The anti-L2 antibody did not occur coincidentally with the antibodies against the HPV 16 early proteins E4 and E7, which are specifically but independently associated with patients with cervical cancer.

[Rectosigmoidectomy following neoadjuvant chemotherapy for advanced ovarian cancer].

Eleven women underwent rectosigmoidectomy as part of an en bloc removal of the adnexal masses, uterus, and pelvic peritoneum during cytoreductive surgery following neoadjuvant chemotherapy for advanced ovarian cancer. While 7 patients with stage IIIc underwent an exploratory laparotomy, 4 cases with stage IV did not because of their poor performance status (PS). Histologic subtypes were as follows: serous, 10 cases; endometrioid, 1 case. Patients with pleural effusion and ascites received immunotherapy. Thereafter, all patients were treated with 4-6 courses of neoadjuvant chemotherapy with cisplatin containing combinations, which delivered 9 PR, 1 MR and 1 NC. The PS score was improved by neoadjuvant chemotherapy and immunotherapy which may contribute to the low mortality and morbidity. Residual tumor of the largest diameter after debulking surgery were as follows: absent (5 cases), present (< 0.5cm; 2 cases, < 2cm; 3 cases, > or = 2cm; 1 case). The median survival for the entire group was 32.6 months. None of the 7 cases with residual disease < 0.5cm died of the disease within 2 years. Rectosigmoidectomy following neoadjuvant chemotherapy might be a useful procedure for patients who will be left with minimal residual disease after completion debulking surgery.