Clinical effectiveness of four neuraminidase inhibitors (oseltamivir,zanamivir, laninamivir,and peramivir) for children with influenza A and B in the 2014–2015 to 2016–2017 influenza seasons in Japan

The clinical effectiveness of four neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, laninamivir, and peramivir) for children aged 0 months to 18 years with influenza A and B were investigated in the 2014–2015 to 2016–2017 influenza seasons in Japan. A total of 1207 patients (747 with influenza A and 460 with influenza B) were enrolled. The Cox proportional-hazards model using all of the patients showed that the duration of fever after administration of the first dose of the NAI was shorter in older patients (hazard ratio = 1.06 per 1 year of age, p < 0.001) and that the duration of fever after administration of the first dose of the NAI was shorter in patients with influenza A infection than in patients with influenza B infection (hazard ratio = 2.21, p < 0.001). A logistic regression model showed that the number of biphasic fever episodes was 2.99-times greater for influenza B-infected patients than for influenza A-infected patients (p < 0.001). The number of biphasic fever episodes in influenza A- or B-infected patients aged 0–4 years was 2.89-times greater than that in patients aged 10–18 years (p = 0.010), and the number of episodes in influenza A- or B-infected patients aged 5–9 years was 2.13-times greater than that in patients aged 10–18 years (p = 0.012).     

Results of triple eradication therapy in Japanese children: a retrospective multicenter study

Background Large-scale clinical trials in children are lacking concerning Helicobacter pylori eradication therapies. The purpose of this study was to assess the efficacy of proton pump inhibitor (PPI)-based triple therapies in Japanese children.Methods This was a retrospective analysis of the first- and second-line PPI-based triple therapies from pediatric gastrointestinal units between 1996 and 2003. Data collected included doses and duration of regimens, drug compliance, success or failure of eradication, ulcer healing, and symptom response of those with dyspepsia and no ulcers. The results of antibiotic susceptibility tests were also reported in cases where these were performed.Results A total of 149 pediatric patients (mean age, 12.6 years) were studied, including 123 patients who received first-line therapy: 115 received a PPI plus amoxicillin and clarithromycin (PAC) and 8 received a PPI plus amoxicillin and metronidazole (PAM). Overall eradication rates of the first-line PAC and PAM therapies were 77.4% and 87.5%, respectively (P = 0.68). All 14 patients with failed PAC therapy received the second-line PAM regimen, resulting in an eradication rate of 100%. Mild side effects were reported only in PAC regimens (13.8%). Primary resistance to amoxicillin, clarithromycin, and metronidazole was detected in 0%, 34.7%, and 12.5% of the strains, respectively. The PAC regimen showed a high eradication rate for clarithromycin-susceptible strains (91.7%), but was relatively ineffective for resistant strains (40.0%) (P < 0.01). Eradication of H. pylori was associated with ulcer healing and symptomatic improvement among those with gastritis only (both; P < 0.001). Among 17 patients with iron-deficiency anemia, post-treatment hemoglobin levels were higher than the pretreatment levels (P < 0.001).Conclusions The PAC regimen is effective in children. Clarithromycin resistance is associated with eradication failure. Metronidazole is a good substitute for clarithromycin as the second-line option for children.     

Gamma/delta T cell lymphoma

A 54-year-old woman complained of fever and hepato-splenomegaly. The pathological findings of a liver biopsy specimen revealed the infiltration of lymphocytes in the sinusoids and that of the laparoscopically resected spleen revealed the infiltration of lymphocytes in the red pulp, which was positive for CD3, CD43, CD45RO and T-cell intracellular antigen-1 (TIA-1) and was negative for betaF1, while the white pulp was spared. Genetic analysis of the spleen cells revealed the rearrangement of T-cell receptor (TCR) Cbeta1, Jdelta1 and Jgamma. Epstein-Barr virus (EBV) genomic DNA was detected in the spleen cells. Atypical lymphocytes appeared in the peripheral blood and bone marrow, chromosomal analysis revealed del (13) (q12 q14), trisomy 8 and breakage of RB gene. Elevated level of serum vascular endothelial growth factor (VEGF) was observed. Hepatosplenic gammadelta T cell lymphoma (GDTL) was diagnosed. The patient was treated with chemotherapy by cyclophosphamide, hydroxydoxorubicin, vincristine and prednisolone (CHOP), however, it was ineffective, and the patient died of hemorrhage from the lymphoma involvement of the intestine 5 months after the onset of disease.     

Comparing the Acid-Suppressive Effects of Three Brands of Generic Lansoprazole with the Original: Pharmacokinetic Bioequivalence Tests Do Not Necessarily Guarantee Pharmacodynamic Equivalence

Generic drugs contain the same active ingredient as an original drug and have their bioequivalence proved by pharmacokinetic tests. However, few studies have been reported on whether these bioequivalence studies infer pharmacodynamic equivalence. In this study, in eight healthy Helicobacter pylori-negative CYP2C19 extensive metabolizers, we compared the acid-suppressive effects of repeated administration of 15 mg of three brands of generic lansoprazole, Taiproton, Tapizol, and Lansoral, with those of the original lansoprazole, Takepron. Median intragastric pH value for 24-h and % pH > 4 for daytime (08:00–20:00 h) and night-time were significantly higher with any lansoprazole formulation, compared with the control (P < 0.05, Wilcoxon signed-rank test). However, during the daytime, % pH > 4 with Tapizol was significantly lower than the original (P < 0.05). Compared with the original, no significantly larger, but no small range of inter-subject variations were observed in these two parameters for each of the three brands of generic lansoprazole (Bartlett test). Pharmacokinetic bioequivalence tests do not necessarily guarantee pharmacodynamic equivalence.     

Submacular exudates with serous retinal detachment caused by cat scratch disease

Purpose: To present submacular exudates as a manifestation of cat scratch disease. Methods: Report of two cases. Results: The first patient, a 34-year-old man, developed submacular exudates with serous retinal detachment ten days after having axillary lymphadenopathy and fever. The second patient, a 30-year-old woman, developed submacular exudates with serous retinal detachment mimicking central serous chorioretinopathy. Fluorescein angiography revealed late staining of the subretinal lesions in both cases.The lesion resolved spontaneously in the first patient, while sulfamethoxazole and trimethoprim was required for the second patient. Both patients had a positive IgG titer for Bartonella henselae. Conclusions: Submacular exudates with serous retinal detachment can occur in cat scratch disease. Cat scratch disease should be included in the differential diagnosis of submacular exudates with central serous chorioretinopathy.     

Epinephrine inhibits invasion of oral squamous carcinoma cells by modulating intracellular cAMP.

In oral and maxillofacial surgery, epinephrine is routinely used for cancer resection and it is important to clarify the effects of this agent on cancer. We found here that the clinically relevant concentrations of epinephrine (10, 50 and 100 microg/ml) decreased the invasion ability of oral squamous carcinoma (Sa3) cells. In the Sa3 cells treated with epinephrine (10, 50 and 100 microg/ml), migration, morphological changes and formation of actin stress fibers were inhibited and intracellular cyclic adenosine monophosphate (cAMP) increased significantly. These findings suggest that epinephrine inhibits the invasion of cancer cells by modulating intracellular cAMP and that clinicians could use epinephrine effectively for the surgical resection of the cancer.     

Inhibition of transendothelial migration and invasion of human breast cancer cells by preventing geranylgeranylation of Rho

Rho family GTPases are frequently overexpressed in breast cancers, which regulate cancer cell migration and invasion. They require prenylation, a lipid post-translational modification, for full biological functions. We examined the effects of 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (fluvastatin), a selective farnesyltransferase inhibitor (FTI-277) and a selective geranylgeranyltransferase type I inhibitor (GGTI-298) on in vitro invasive capacity of MDA-MB-231 human breast cancer cells into the endothelial cell monolayer in a transendothelial migration assay. Although, at a maximal dose of 5 microM, fluvastatin did not affect the integrity of endothelial cell monolayer, the transendothelial migration of MDA-MB-231 cells was inhibited potently by fluvastatin in a dose-dependent manner. The transendothelial migration of MDA-MB-231 cells was also inhibited potently by GGTI-298 in a dose-dependent manner but weakly by FTI-277. The inhibitory effects of fluvastatin, GGTI-298 and FTI-277 on MDA-MB-231 cell invasion were shown to correlate well with inhibition of the membrane localization of RhoA and RhoC, but not with Ras. These results suggest that geranylgeranylation step of RhoA and RhoC could be a good therapeutic target for the prevention of invasion and metastasis of breast cancer cells.