An evaluation of mass screening for breast cancer

In Tokushima Prefecture, Japan, 41,922 women (26,669 in actual number) were subjected to mass screening with physical examination from 1970–1977. In 42 including 10 of so-called “interval cancer”, breast cancer was detected. Those with breast cancer detected by mass screening were in the earlier stage of the discase as compared to those diagnosed through regular medical care at our out-patient clinic during the same period. Procedures such as inspection and palpation are readily carried out and early occurrences of breast cancer can be detected.     

Synergistic effect of fosfomycin and fluoroquinolones against Pseudomonas aeruginosa growing in a biofilm

Ulifloxacin is the active form of the prodrug prulifloxacin and shows a highly potent antipseudomonal activity. In this study, we examined the combined effect of fosfomycin and ulifloxacin against Pseudomonas aeruginosa (P. aeruginosa) growing in a biofilm using a modified Robbins device with artificial urine, and compared it to that of the combination of fosfomycin and ciprofloxacin or levofloxacin. An ATP bioluminescence assay was used to evaluate the antibacterial activity of the agents against sessile cells in a mature biofilm developed on a silicon disk. The total bioactivity of P. aeruginosa growing in a biofilm that had not been fully eradicated by fosfomycin or any of the fluoroquinolones alone at 10 times the MIC decreased after combination treatment with fosfomycin and fluoroquinolones. Morphological changes occurred in a time-dependent fashion; namely, swollen and/or rounding cells emerged within a couple of hours after combination treatment, marking the initial stage in the process leading to the destruction of the biofilms. We could not find any difference among the 3 fluoroquinolones with regard to their synergistic effects when administered with fosfomycin. The combination treatment of fosfomycin and fluoroquinolones with highly potent antipseudomonal activities was effective in eradicating sessile cells of P. aeruginosa in the biofilm and promises to be beneficial against biofilm-associated infectious diseases.     

Combined use of a magnifying endoscope with a narrow band imaging system and a multibending endoscope for en bloc EMR of early stage gastric cancer

BACKGROUND: En bloc EMR is performed in Japan as a curative treatment for early stage gastric cancer. However, current methods of EMR are technically difficult and require proficiency in determining the extent of the cancer. This study assessed the feasibility of a new method to obviate these problems and to facilitate en bloc EMR. METHODS: The new method uses two types of endoscopes: a magnifying endoscope with a narrow band imaging system to enhance the definition of mucosal and microcirculatory structure, and an endoscope with multibending tip deflection to maintain orientation during EMR. Forty-two consecutive cases of mucosal gastric cancer treated by EMR were reviewed retrospectively. In 12 of these patients, 12 lesions that fulfilled guideline criteria for EMR were treated by the modified, en bloc EMR method of circumferential incision and snare resection by using the two endoscopes. RESULTS: The rate of complete en bloc resection with the new method of EMR was 91.7%, (11/12). There was no major complication. CONCLUSIONS: The new en bloc resection method for EMR with two endoscopes described here is feasible and may be a safe and a reliable technique for curative treatment of mucosal gastric cancer.     

Cyclosporine A for chemotherapy-resistant subcutaneous panniculitis-like T cell lymphoma with hemophagocytic syndrome

Subcutaneous panniculitis-like T cell lymphoma (SPTL) is a rare subtype of non-Hodgkin lymphoma for which a definitive therapeutic strategy has not been established yet. We report a case of chemotherapy-resistant SPTL with hemophagocytic syndrome (HPS) which was successfully treated with cyclosporine A (CsA) plus methylprednisolone (mPSL), and also reviewed 11 SPTL cases treated with CsA, previously reported in the literature. Our patient was a 38-year-old female with SPTL. The disease progressed despite conventional chemotherapy using cytotoxic agents including alkylators, anthracyclins or purine analogues, and, after 2 months of chemotherapy, was eventually complicated by HPS and disseminated intravascular coagulation (DIC). CsA (4 mg/kg/day) plus mPSL treatment dramatically improved HPS with DIC, reduced subcutaneous tumors within 2 weeks, and finally induced complete remission (CR) after 3 months. Currently, the patient has maintained CR while being treated with CsA for 12 months. In addition to our case, 9 of 11 SPTL cases were successfully treated with CsA, and 8 were induced to CR. Time to first response to CsA was within 2 weeks in most cases, regardless of prior treatment or the co-occurrence of HPS. Our case and this first comprehensive review on CsA for SPTL suggest that CsA may constitute a candidate treatment strategy for SPTL.     

Duration of the metronidazole-containing regimen for eradication of Helicobacter pylori infection in northern Japan

Metronidazole is often used to eradicate clarithromycin-resistant Helicobacter pylori. The aim of this study was to determine the appropriate duration of metronidazole-containing treatment for the eradication of H. pylori infection in northern Japan. We enrolled 83 H. pylori-positive patients in whom first-line triple therapy consisting of a proton pump inhibitor, amoxicillin and clarithromycin had failed. Prior to the second-line therapy, patients underwent endoscopy to obtain H. pylori strains to test the susceptibility to antibiotics. Patients were administered lansoprazole (30 mg b.d.), amoxicillin (750 mg b.d.) and metronidazole (250 mg b.d.) for 5 or 7 days, and the treatment results were tested by (13)C-UBT. None of the isolated H. pylori strains was amoxicillin- or metronidazole-resistant. All the patients completed the regimen without major adverse effects. The eradication rate was 95.1% (39/41; 95% confidence interval [CI], 83.5-99.4%) in the 41 patients who were treated for 5 days and 95.2% (40/42; 95% CI, 83.8-99.4%) in the 42 patients treated for 7 days. The results suggest that 5 days could be a sufficient duration for triple therapy of lansoprazole, amoxicillin and metronidazole as a second-line H. pylori eradication therapy in areas where metronidazole-resistant strains are rare.     

Fetal thymus graft prevents age-related hearing loss and up regulation of the IL-1 receptor type II gene in CD4(+) T cells

Monocytes play an important role in hemostasis. In this study, the prothrombotic effects of the neuropeptide substance P (SP) on human monocytes through neurokinin-1 receptor (NK1-R) were characterized. SP upregulated monocyte tissue factor (TF), the major coagulation cascade stimulator, in a concentration and time dependent manner. Specific inhibition of NK1-R completely blocked TF expression. Monocytes stimulated by SP released cytokines and chemokines. When monocytes were stimulated with cytokines or chemokines, TF was expressed by the cytokines (GM-CSF, IFN-γ and TNF-α). Cytokines may play a major role in the mechanism of SP induced monocyte TF expression. NK1-R antagonists (NK1-RA) may have a role in developing novel therapeutic approaches to patients vulnerable to vaso-occlusive disorders.     

Effect of coadministration of M-CSF and IFN-alpha on NK1.1+ cells in mice.

The purpose of this study was to evaluate the effect of coadministration of macrophage colony-stimulating factor (M-CSF) and interferon-alpha (IFN-alpha) on NK1.1(+) cells in mice. Administration of M-CSF, but not IFN-alpha, increased the number of NK1.1(+) cells and CD11b(+) cells in spleen and blood. Coadministration of the two agents induced a greater increase in NK1.1(+) cells than did administration of M-CSF alone. Administration of M-CSF or IFN-alpha augmented the clearance activity of Yac-1 cells in lung, and coadministration of these agents further augmented this effect. The combination of M-CSF and IFN-alpha effectively reduced the formation of tumor nodules in lung and liver in an experimental metastasis model using B16 melanoma. The combination of M-CSF and IFN-alpha induced the increase and activation of NK1.1(+) cells more than either agent alone. These effects may contribute to the antimetastatic reaction by NK1.1(+) cells in vivo.     

Liposome‐Encapsulated Hemoglobin Accelerates Skin Wound Healing in Diabetic dB/dB Mice

Since liposome‐encapsulated hemoglobin with high O₂ affinity (h‐LEH, P₅₀O₂ = 10 mm Hg) has been reported to accelerate skin wound healing in normal mice, it was tested in dB/dB mice with retarded wound healing, as seen in human diabetics. Two full‐thickness dorsal wounds 6 mm in diameter encompassed by silicone stents were created in dB/dB mice. Two days later (day 2), the animals were randomly assigned to receive intravenous h‐LEH (2 mL/kg, n = 7) or saline (2 mL/kg, n = 7). The same treatment was repeated 4 days after wounding (day 4), and the size of the skin lesions was analyzed by photography, surface perfusion was detected by Laser‐Doppler imager, and plasma cytokines and chemokines were determined on days 0, 2, 4, and 7, when all animals were euthanized for morphological studies. The size of the ulcer compared to the skin defect or silicone stent became significantly reduced on days 4 and 7 in mice treated with h‐LEH (47 ± 8% of original size), similar to the level in wild‐type mice, compared to saline‐treated dB/dB mice (68 ± 18%, P < 0.01). Mice treated with h‐LEH had significantly attenuated inflammatory cytokines, increased surface perfusion, and increased Ki67 expression on day 7 in accordance with the ulcer size reduction, while there was no significant difference in chemokines, histological granulation, epithelial thickness, and granulocyte infiltration detected by immunohistochemical staining in the ulcer between the treatment groups. The results suggest that h‐LEH (2 mL/kg) early after wounding may accelerate skin wound healing in dB/dB mice to levels equivalent to wild‐type mice probably via mechanism(s) involving reduced hypoxia, increased surface perfusion, suppressed inflammation, accelerated in situ cell proliferation and protein synthesis.