We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the ¹³C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to follow-up. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%, respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.
TAS-108 is a novel steroidal anti-oestrogen, expected to be useful for the treatment of breast cancer. The present study was conducted to investigate the safety, tolerability and pharmacokinetics of TAS-108 following the administration at a single oral dose of 40 mg to up to 120 mg in 12 post-menopausal women and the effect of food on the pharmacokinetics of the drug. All adverse events were mild and involved transient symptoms that resolved without therapeutic intervention. TAS-108 was readily absorbed and plasma levels of TAS-108 steadily declined, apparently in a multi-exponential manner. C max and AUC 0-12 were proportionally increased with increasing dose of TAS-108. The C max and AUC 0-t of TAS-108 and its metabolite, deEt-TAS-108, were significantly increased to approximately 150% when TAS-108 was administered after a meal. Food did not affect the elimination half-life of TAS-108 or its metabolites. In this escalating dose-study of TAS-108, the drug was well tolerated by healthy post-menopausal Japanese women. The pharmacokinetics of TAS-108 indicated dose proportionality, and its bioavailability was significantly increased by food intake.New breast cancer cases and deaths due to breast cancer reported in 2008 were estimated to be 184,450 and over 40,930, respectively, in the United States [1]. Although breast cancer incidence rates have continued to increase in Japan [2] to the same extent as in USA, the mortality rates have declined in these and several other countries during the 1990s due to more effective therapies and early detection of breast cancer [1,3]. Many chemotherapies and endocrine therapies have been used to treat breast cancer in the neoadjuvant and adjuvant setting as well as to prevent breast cancer. Endocrine therapy is a standard care for the treatment of post-menopausal women with oestrogen receptor-and/or progesterone receptor-positive breast cancer. Endocrine therapy in these patients is as effective as chemotherapy in terms of relapse-free status and overall survival, and its adverse effects are fewer and less severe than those of chemotherapy [3,4]. The selective oestrogen receptor modulator (SERM), tamoxifen, has been in use for the treatment of advanced breast cancer for more than 30 years and is currently a treatment option for all stages of oestrogen receptor-positive diseases regardless of the menopausal status of the patient [4,5]. As found from several large clinical trials such as the ATAC trial, , aromatase inhibitors such as anastrozole, letrozole and exemestane have been shown to be clinically superior to tamoxifen on the efficacy for post-menopausal patients. These inhibitors do not have the many risks [11,12] and they do not have favourable agonistic properties towards oestrogen receptors as long-term tamoxifen treatment [13,14], which has the preservation of bone mineral density and favourable effect on the cardiovascular risk in post-menopausal women. On the other hand, most breast cancer patients acquire resistance to tamoxifen after longterm use, as indi...
We investigated the clinical and laboratory data of 215 hospitalized patients (mean age were 76.9 +/- 12.1) to analyze both the characteristics of senile UTI and the influence of the way of urination. UTI was present in 121 of 1897 patients (6.4%), 95 of whom (78.5%) were female. Comparison of the parameters between non-infected and infected patients were as follows: body temperature was 36.57 +/- 0.64 degrees C vs. 37.49 +/- 0.77 degree C; WBC, 5410 +/- 2040/microliters vs. 7260 +/- 3230/microliters; CRP, 1.2 +/- 2.4 mg/dl vs. 3.5 +/- 3.4 mg/dl; mean class of urinary RBC, 0-1/hpf vs. 3-5/hpf; and mean class of urinary WBC, 5-10/hpf vs. 30-50/hpf. All parameters were significantly elevated (p < 0.001) in the patients with UTI. The rate of detection of causative bacteria was 88.7%; with 14.8% Escherichia coli, 12.8% Providencia species, 9.6% Enterococci, and 8.7% Pseudomonas aeruginosa. Patients with UTI were divided into three groups according to their method of urination: normal urination, use of diapers and catheterization. Body temperature (> or = 37.5 degrees C) was 2.8%, 10.1% and 34.9%; WBC (> or = 9.000), 2.7%, 6.1%, and 14.3%; CRP, 16.9%, 36.1% and 51.1%; urine RBC (> or = 6-10/hpf), 8.4%, 7.1% and 36.1%; urine WBC (> or = 15-30/hpf), 20.4%, 44.4% and 76.9%, respectively. There was a significant difference (p < 0.05-0.001) between all parameters except for urine RBC between the normal-urination patients and diaper using patients. This investigation suggested that the use of diapers was a risk factor for UTI in elderly patients.
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