Effect of renin-angiotensin system inhibitors on pemetrexed plus platinum-induced hematological toxicities: a multicenter retrospective study using three propensity score analyses.

Hematological toxicities induced by pemetrexed plus platinum therapy remain a critical issue in clinical practice. We hypothesized that inhibition of the renin-angiotensin system (RAS) can ameliorate pemetrexed-induced hematological toxicities through drug-drug interactions involving organic anion transporters. Thus, this study aimed to clarify whether RAS inhibitors (RASIs) could prevent pemetrexed plus platinum-induced hematological toxicities. We retrospectively analyzed data from 305 consecutive patients with non-small cell lung cancer or malignant pleural mesothelioma who received their first cycle of a pemetrexed plus platinum regimen and were treated with or without RASIs. The primary endpoint was the incidence of severe myelosuppression after the first cycle. Propensity score (PS)-matched, PS-adjusted, and inverse probability of treatment weighting (IPTW) analyses were used. The number of patients with grade ≥3 hematological toxicities was 27 (8.9%). PS-matched analyses revealed that the concomitant use of RASIs was slightly associated with a lower risk of grade ≥3 hematological toxicities (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.20-2.32; p = 0.536). Additionally, sensitivity analyses using PS-adjusted and IPTW methods demonstrated similar results (OR, 0.63; 95% CI, 0.19-2.15; p = 0.463 and OR, 0.37; 95% CI, 0.11-1.29; p = 0.117, respectively). These findings suggest that RASIs might prevent pemetrexed plus platinum-induced hematological toxicities.

Laser Spectroscopy of Neutron-Rich

The mean-square charge radii of ^{207,208}Hg (Z=80, N=127, 128) have been studied for the first time and those of ^{202,203,206}Hg (N=122, 123, 126) remeasured by the application of in-source resonance-ionization laser spectroscopy at ISOLDE (CERN). The characteristic kink in the charge radii at the N=126 neutron shell closure has been revealed, providing the first information on its behavior below the Z=82 proton shell closure. A theoretical analysis has been performed within relativistic Hartree-Bogoliubov and nonrelativistic Hartree-Fock-Bogoliubov approaches, considering both the new mercury results and existing lead data. Contrary to previous interpretations, it is demonstrated that both the kink at N=126 and the odd-even staggering (OES) in its vicinity can be described predominately at the mean-field level and that pairing does not need to play a crucial role in their origin. A new OES mechanism is suggested, related to the staggering in the occupation of the different neutron orbitals in odd- and even-A nuclei, facilitated by particle-vibration coupling for odd-A nuclei.

Review of clinical studies on the nocebo effect.

Objective: To review clinical studies on the nocebo effect. PubMed was searched for relevant clinical studies as well as studies on the relationship between the nocebo effect and genes. Data sources: A total of 35 clinical studies on the nocebo effect and one study on its relationship with genes were selected for review. All were conducted outside Japan. Results and conclusion: An increasing number of clinical studies on the nocebo effect are being published. The 36 studies selected for review were grouped into the following five categories: (1) studies of how differences in participant characteristics such as personality affect susceptibility to the nocebo effect, (2) studies of how differences in provision of information about side effects affect susceptibility to the nocebo effect, (3) studies of how nocebo conditioning affects susceptibility to the nocebo effect, (4) studies of nocebo response mechanisms, and (5) studies of the nocebo effect and genetic polymorphisms. The first four categories comprised 5, 19, 8, and 3 studies, respectively, and the fifth comprised 1 study. Most of the studies investigated how differences in the provision of information affect susceptibility to the nocebo effect. Few studies investigated individual differences in the nocebo effect (differences between responders and non-responders) or mechanisms of the nocebo effect.

Quantitative Survey of Laypersons' Attitudes Toward Organ Transplantation in Japan.

BACKGROUND: In comparison with foreign countries, living-organ transplantations (LOT) have been performed more frequently than dead organ transplants, including brain-dead organ transplantation (BOT) in Japan. This situation has given rise to organ transplantation tourism. Therefore, we clarify laypersons' preferences regarding organ transplantation that are producing the current situation in Japan, to suggest a possible framework for further efforts. METHODS: Voluntary completion of a quantitative and anonymous survey was promoted online (a sample size of 1030). The questionnaire had two types of variables concerning demographic characteristics and organ transplantation-related issues. RESULTS: LOT was favored over BOT. However, for willingness to donate to family members, the participants showed a significantly more positive attitude toward brain-dead organ donors (BODs) than living organ donors (LODs). In the evaluation of each transplantation technology, BOT and LOT were positioned in the middle, between transplantation that does not depend on others and the utilization of animal organs. CONCLUSIONS: Although LOT was favored over BOT, for participants hypothesized to be in a position to donate and receive organs, BODs received a conversely better reputation than LODs. Our survey and discussion suggest that the present conditions of organ transplantation in Japan might be because there is a lack of deliberation on transplantation tourism and LOT. Therefore, more surveys concerning LOT cases and the implications of avoidance of organs from brain-dead bodies, coupled with more discussions based on these surveys, are necessary to formulate a Japanese transplantation policy for the future.

Nonquenched Isoscalar Spin-M1 Excitations in sd-Shell Nuclei.

Differential cross sections of isoscalar and isovector spin-M1 (0(+)→1(+)) transitions are measured using high-energy-resolution proton inelastic scattering at E(p)=295 MeV on (24)Mg, (28)Si, (32)S, and (36)Ar at 0°-14°. The squared spin-M1 nuclear transition matrix elements are deduced from the measured differential cross sections by applying empirically determined unit cross sections based on the assumption of isospin symmetry. The ratios of the squared nuclear matrix elements accumulated up to E(x)=16 MeV compared to a shell-model prediction are 1.01(9) for isoscalar and 0.61(6) for isovector spin-M1 transitions, respectively. Thus, no quenching is observed for isoscalar spin-M1 transitions, while the matrix elements for isovector spin-M1 transitions are quenched by an amount comparable with the analogous Gamow-Teller transitions on those target nuclei.

Potential for acceleration of bone formation after implant surgery by using a dietary supplement: an animal study.

Dental implant treatment is an effective modality to restore lost aesthetic and masticatory functions. However, healing after implant surgery takes at least 3-6 months. This prolonged healing period poses several difficulties for individuals with a large edentulous area and decreases their quality of life. Consequently, shortening the healing period and accelerating final prosthesis placement after surgery is very clinically important. Peri-implant bone formation may be enhanced by systemic approaches, such as the use of osteoporosis supplements, to promote bone metabolism. To confirm whether intake of a supplement developed for osteoporosis, synthetic bone mineral (SBM), was effective in accelerating peri-implant bone formation as part of the healing process after implantation. Twenty-four 5-week-old female Wistar rats were randomly assigned to receive a standardised diet without (control group, n = 12) or with SBM (n = 12). The rats had implant surgery at 8 weeks of age under general anaesthesia. The main outcome measures were bone mineral density (BMD) and pull-out strength in the implant and femur, which were compared between the groups at 2 and 4 weeks after implantation using the Mann-Whitney U test. BMD was significantly greater in the SBM group at 2 and 4 weeks after implantation compared to the control group. Pull-out strength was significantly greater in the SBM groups at 2 and 4 weeks after implantation compared to the control group. This study demonstrated that SBM could be effective in accelerating peri-implant bone formation during the healing period after implantation.

Crossover from vibrational to rotational collectivity in heavy nuclei in the shell-model Monte Carlo approach.

Heavy nuclei exhibit a crossover from vibrational to rotational collectivity as the number of neutrons or protons increases from shell closure towards midshell, but the microscopic description of this crossover has been a major challenge. We apply the shell model Monte Carlo approach to families of even-even samarium and neodymium isotopes and identify a microscopic signature of the crossover from vibrational to rotational collectivity in the low-temperature behavior of ⟨J(2)⟩(T), where J is the total spin and T is the temperature. This signature agrees well with its values extracted from experimental data. We also calculate the state densities of these nuclei and find them to be in very good agreement with experimental data. Finally, we define a collective enhancement factor from the ratio of the total state density to the intrinsic state density as calculated in the finite-temperature Hartree-Fock-Bogoliubov approximation. The decay of this enhancement factor with excitation energy is found to correlate with the pairing and shape phase transitions in these nuclei.

Separation of pygmy dipole and M1 resonances in 90Zr by a high-resolution inelastic proton scattering near 0°.

A high-resolution measurement of inelastic proton scattering off (90)Zr near 0° was performed at 295 MeV with a focus on a pronounced strength previously reported in the low-energy tail of giant dipole resonance. A forest of fine structure was observed in the excitation energy region 7-12 MeV. A multipole decomposition analysis of the angular distribution for the forest was carried out using the ECIS95 distorted-wave Born approximation code with the Hartree-Fock plus random-phase approximation model of E1 and M1 transition densities and inclusion of E1 Coulomb excitation. The analysis separated pygmy dipole and M1 resonances in the forest at E(PDR)=9.15±0.18 MeV with Γ(PDR)=2.91±0.64 MeV and at E(M1)=9.53±0.06 MeV with Γ(M1)=2.70±0.17 MeV in the Lorentzian function, respectively. The B(E1)↑ value for pygmy dipole resonance over 7-11 MeV is 0.75±0.08 e(2)fm(2), which corresponds to 2.1±0.2% of the Thomas-Reiche-Kuhn sum rule.

Effects of two monoclonal antibodies, MLS128 against Tn-antigen and 1H7 against insulin-like growth factor-I receptor, on the growth of colon cancer cells.

MLS128 is an anti-carbohydrate monoclonal antibody (mAb) that binds three or two consecutive Tn-antigens. MLS128 bound 110-210 kDa glycoproteins (GPs) and inhibited the growth of LS180 and HT29 colon and MCF-7 breast cancer cells. One possible mechanism of MLS128's inhibition of growth may be via insulin-like growth factor-I receptor (IGF-IR) down-regulation (Morita et al. BioScience Trends. 2009; 3:32-37). The current study examined the role of IGF-IR signaling in the growth of colon cancer cells and its possible interaction with MLS128-induced inhibition of cell growth in LS180, LS174T, and HT29 human colon cancer cells treated with MLS128 or anti-IGF-IR 1H7. Both MLS128 and 1H7 treatment significantly inhibited the growth of colon cancer cells. All three colon cancer cell lines expressed IGF-IR. Their growth was in part IGF-I dependent, but inhibition by MLS128 was independent of IGF-IR signaling. All of the colon cancer cell lines expressed an 110kDa GP for MLS128 binding, but MCF-7 cells expressed MLS128-detectable bands with higher molecular masses. 1H7 treatments caused down-regulation of IGF-IR but did not affect 110kDa GP levels. MLS128 treatments resulted in partial disappearance of the 110kDa band but did not affect IGF-IR levels. Western blotting analyses of colon and breast cancer cell lysates revealed that colon and breast cancer cells differed significantly in patterns of expression of growth-related molecules while colon cancer cells were similar but distinctive. In conclusion, MLS128 inhibited the growth of colon cancer cells by binding to the 110kDa GP receptor. Inhibition of growth by MLS128 did not appear to affect IGF-IR signaling and instead only affected other growth signaling pathways.

Resection of stage 0/I colon cancer via a circumferential periumbilical skin incision: relevance to single-incision laparoscopic surgery.

BACKGROUND: We have been performing curative resection of colon cancer via a minilaparotomy without utilizing any laparoscopic instruments as an alternative to laparoscopic-assisted approach. Based on our experiences and improved surgical techniques, we have devised a new method for performing resection of stage 0/I colon cancer via a circumferential periumbilical skin incision that is associated with better cosmesis than standard minilaparotomy. METHODS: The short- and long-term results of curative colectomy via a circumferential periumbilical skin incision without utilizing any laparoscopic instruments performed in selected patients with stage 0/I colon cancer between October 2003 and July 2004 were analyzed. RESULTS: There were 8 men and 2 women with a median age of 66.5 years (range 61-77 years). Their median body mass index was 22.4 kg/m(2) (range 21.1-27.7 kg/m(2)). Pathological stage according the TNM classification was stage 0 in 4 patients and stage I in 6 patients. Median operative time was 160.5 min (range 135-203 min), and median blood loss was 60 ml (range 5-330 ml). Postoperative complications consisted of seroma in two patients and small bowel obstruction in one patient. After a median follow-up period of 5.7 years, there were no recurrences or wound complications. CONCLUSION: Curative colectomy via a circumferential periumbilical skin incision seems oncologically safe, yields satisfactory cosmetic results, and may provide an alternative to single-incision laparoscopic surgery in selected patients with colon cancer.

Expression of Tn and sialyl Tn antigens in synovial tissues in rheumatoid arthritis.

OBJECTIVES: The carbohydrate chains represented by mucins (MUCs) are expressed by a variety of normal and malignant secretory epithelial cells and induce a variety of immunoreactions. Tn and sialyl Tn antigens are tumour-associated carbohydrate antigens which are borne on the core proteins of mucins. The purpose of this study is to investigate the existence of tumour-associated carbohydrate antigens in rheumatoid arthritis (RA). METHODS: . We examined the expression of Tn and sialyl Tn antigens in synovial tissues from RA and osteoarthritis (OA) patients by immunohistochemistry. In addition, mucins from synovial fluid (SF) from RA patients are purified by gel filtration and density gradient ultracentrifugation and the existence of these antigens examined by dot and Western blotting. RESULTS: We found that Tn and sialyl Tn antigens were strongly expressed in synovial cells and infiltrating mononuclear cells on the sublining layer and lymphoid follicles in synovial tissues in RA compared with those in osteoarthritis. Tn and sialyl Tn antigens were detected in purified mucins of SF from RA patients. CONCLUSIONS: Tumour-like synovial hyperplasia cells expressed Tn and sialyl Tn antigens. This finding suggests that the mucins exhibiting with abnormal glycosylation may be in part responsible for synovial hyperplasia, leading to the joint destruction in the pathogenesis of RA.

When should we intervene to control the 2009 influenza A(H1N1) pandemic?

We simulated the early phase of the 2009 influenza A(H1N1) pandemic and assessed the effectiveness of public health interventions in Japan. We show that the detection rate of border quarantine was low and the timing of the intervention was the most important factor involved in the control of the pandemic, with the maximum reduction in daily cases obtained after interventions started on day 6 or 11. Early interventions were not always effective.

Heavy deformed nuclei in the shell model Monte Carlo method.

We extend the shell model Monte Carlo approach to heavy deformed nuclei using a new proton-neutron formalism. The low excitation energies of such nuclei necessitate low-temperature calculations, for which a stabilization method is implemented in the canonical ensemble. We apply the method to study a well-deformed rare-earth nucleus, 162Dy. The single-particle model space includes the 50-82 shell plus 1f_{7/2} orbital for protons and the 82-126 shell plus 0h_{11/2}, 1g_{9/2} orbitals for neutrons. We show that the spherical shell model reproduces well the rotational character of 162Dy within this model space. We also calculate the level density of 162Dy and find it to be in excellent agreement with the experimental level density, which we extract from several experiments.

Spin projection in the shell model monte carlo method and the spin distribution of nuclear level densities.

We introduce spin projection methods in the shell model Monte Carlo approach and apply them to calculate the spin distribution of level densities for iron-region nuclei using the complete (pf + g9/2) shell. We compare the calculated distributions with the spin-cutoff model and extract an energy-dependent moment of inertia. For even-even nuclei and at low excitation energies, we observe a significant suppression of the moment of inertia and odd-even staggering in the spin dependence of level densities.

Influence of different pneumoperitoneal pressures on tumor cell distribution in rats.

BACKGROUND: The effect of different pneumoperitoneal pressures on tumor cell distribution was investigated. METHODS: Donryu rats were allocated to receive carbon dioxide pneumoperitoneum at 5, 10, or 15 mmHg for 60 min or to serve as a control. During the procedure, each rat was inoculated with radiolabeled ascites hepatoma cells via the portal vein (experiment 1) or femoral vein (experiment 2). In both experiments, the rats were killed 30, 60, 90, or 120 min after tumor cell inoculation, and the liver and lungs were extirpated for radioactivity count (n = 5 or 6 for each time point in each group). RESULTS: In experiment 1, the percentage of injected dose (% ID) for the liver was greater than for the other three groups 120 min after tumor cell inoculation. There were no significant differences in the %IDs of the lungs at any time point among the groups. In experiment 2, there were no significant differences in the %IDs of the liver and lungs at any time point among the groups. CONCLUSIONS: These results suggest that an elevated insufflation pressure facilitates the location of intraportally injected tumor cells in the liver, and that pulmonary location of the tumor cells may not depend on insufflation pressures in this animal model.

Minilaparotomy approach for colonic cancer: initial experience of 54 cases.

BACKGROUND: The early outcomes of minilaparotomy for resection of colonic cancer were evaluated. METHODS: In this study, 54 patients (34 Dukes' A, 15 Dukes' B, and 5 Dukes' C) successfully underwent curative resection of colonic cancer via minilaparotomy (skin incision, > or = 7 cm). The major exclusion criteria for this approach required a body mass index greater than 25 kg/m2, a tumor size exceeding 7 cm, a preoperative ileus, and tumor invading the adjacent organs. Patients (n = 54) who had undergone conventional open surgery before the introduction of this technique served as the control group by matching several clinicopathologic factors including body mass index. RESULTS: The passage of flatus (p < 0.01) and the beginning of oral intake (p = 0.02) were earlier, analgesic requirements were lower (p < 0.01), and postoperative serum C-reactive protein levels were lower in the minilaparotomy group (p < 0.01). The blood loss and frequency of postoperative complications did not differ between the groups. CONCLUSION: A minilaparotomy approach is a feasible, minimally invasive, and attractive alternative to conventional laparotomy for selected patients with colonic cancer.

Distribution of intrasplenically injected colon cancer cells following pneumoperitoneum in mice.

BACKGROUND: Few studies have examined tumor cell distribution following laparoscopic surgery for colorectal cancer. We examined the effect of carbon dioxide pneumoperitoneum on the distribution of intrasplenically injected colon cancer cells in mice. METHODS: Mice were intrasplenically injected with 2 x 10(4) colon 26 cells labeled with 111In-oxine and were randomized to undergo pneumoperitoneum at 10 mmHg for 30 min or to receive no treatment other than anesthesia. Radioactivity of the liver, lungs, and spleen was measured 30, 60, 90, or 150 min following tumor inoculation. RESULTS: The dynamic changes in the hepatic radioactivity were not similar between groups. However, the values were not significantly different at any time point. The radioactivity of lungs was extremely low in both groups throughout the experimental period. CONCLUSIONS: Pneumoperitoneum does not appear to cause the accumulation of intraportally spreading tumor cells in the liver, but it may affect the dynamic changes of tumor cells. Also, tumor cell localization in the lungs is negligible in both pneumoperitoneum and control groups.

Gasless laparoscopic surgery for ulcerative colitis and familial adenomatous polyposis:initial experience of 7 cases.

PURPOSE: We evaluated the data on initial experience of gasless laparoscopic surgery for patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). PATIENTS AND METHODS: Seven patients (male/female = 3:4, median age 23, UC/FAP=5:2) underwent gasless laparoscopic total (procto) colectomy. Our basic surgical procedure involved (1) a 6- to 8-cm incision made at the beginning of the operation, (2) the wound pulled upward and/or laterally by retractors, and (3) conventional surgical instruments used through the wound; occasionally laparoscopic assistance and abdominal lifting were employed. The results were compared to those of 7 patients who had undergone conventional open surgery. RESULTS: Oral intake started earlier (p = 0.03) and C-reactive protein level on POD 4 was lower (p = 0.03) in the gasless group than in the control group. Duration of surgery, blood loss, requirement of analgesia, and morbidity rate were not significantly different between the groups. CONCLUSION: Our preliminary results suggest that gasless laparoscopic surgery for UC and FAP is feasible and can be an alternative method for minimally invasive surgery.

Increased insufflation pressure enhances the development of liver metastasis in a mouse laparoscopy model: possible mechanisms.

BACKGROUND: The effect of different insufflation pressures and durations of CO2 pneumoperitoneum on the growth of liver metastasis was investigated in a mouse model. The possible mechanisms involved in the pressure-related enhancement of liver metastasis were also examined. METHODS: Mice inoculated intraportally with colon 26 cells underwent CO2 pneumoperitoneum at different pressures (5,10, or 15 mmHg) for 30 or 60 min, or received no treatment other than tumor cell inoculation (control). The subsequent growth of liver metastases was examined. Mice injected intraportally with 111In-oxine-labeled colon 26 cells underwent pneumoperitoneum at three different pressures or served as controls. The radioactivity of the liver was determined to evaluate tumor accumulation in the liver. Mice received pneumoperitoneum at three different pressures or received trocar placement alone. Changes in plasma interleukin-6 levels were determined. RESULTS: The growth of liver metastases on day 14 was influenced by increased insufflation pressures (p < 0.05) rather than the prolonged duration of pneumoperitoneum without significant interaction. The 15-mmHg pneumoperitoneum group showed a higher (p < 0.05) accumulation of radioactivity in the liver compared with the 5-mmHg pneumoperitoneum group and controls. Pneumoperitoneum groups with 5 and 10 mmHg showed higher (p < 0.05) peak levels of IL-6 compared with controls. CONCLUSIONS: An elevated insufflation pressure plays an important role in the enhancement of liver metastases, and this pressure-related adverse effect may be partly relevant to facilitating accumulation of tumor cells in the liver.

[Effect of peroral doxifluridine plus hepatic arterial infusion for synchronous liver metastasis of colorectal cancer--correlation with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase in primary colorectal cancer lesions].

We investigated whether the efficacy of peroral doxifluridine and hepatic arterial 5-FU infusion on synchronous liver metastasis of colorectal cancer could be predicted based on the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in the primary colorectal lesions. Ten patients with synchronous liver metastasis of colorectal cancer were given doxifluridine (600-800 mg/body/day) orally and 5-FU (500 mg/body, once or twice a week) through the hepatic artery following resection of the primary lesions between June 1996 and July 2001. The levels of TP and DPD in the primary lesions were determined by an enzyme-linked immunosorbent assay. The level of TP, DPD, and the ratio of TP/DPD in patients with partial response (n = 4) were 89.8 +/- 30.0 U/mg protein, 23.5 +/- 25.7 U/mg protein, and 3.8 +/- 1.4, respectively, while those in patients with no response or progressive disease (n = 6) were 41.8 +/- 9.7 U/mg protein, 25.8 +/- 15.8 U/mg protein, and 2.2 +/- 1.6, showing significant difference (p < 0.01) in the level of TP between the groups. These results indicate that determining the level of TS in primary colorectal lesions may be useful for predicting the efficacy of this regimen for patients with synchronous liver metastasis of colorectal cancer.