Factors Associated with Work Efficiency in Home Health Care by Pharmacists.

In recent years, medical staff including physicians and nurses have been participating in home health care, reflecting the needs of an aging society in Japan. Pharmacists are also asked to work on home health care teams to ensure the medical safety of patients. It currently remains unclear whether direct communication, i.e. a meeting, between home-visiting physicians and pharmacists contributes to the proper use of medications and continuous medical care. We retrospectively analyzed the medication management guidance records of home-visited patients who received their first home visit between April 2014 and March 2017. We collected data on pharmacist inquiries, the duration of visits, and details from a meeting between home-visiting physicians and pharmacists. Thirty-five patients were included. At the first visit, the inquiry rate by pharmacists was 65.7%. The prescription question rate was significantly lower in patients with a meeting than in those without (p=0.033). The average duration of visits was significantly shorter for home-visited patients whose health care providers had a meeting (p=0.007). These results suggest that pharmacists who held a meeting with the home-visiting physician before the first patient visit were able to resolve drug-related issues earlier, which increased the work efficiency of home-visiting pharmacists.

Organ differences in the impact of p27(kip1) deficiency on carcinogenesis induced by N-methyl-N-nitrosourea.

To evaluate the impact of p27 on carcinogenesis in various organs, N-methyl-N-nitrosourea (MNU), a direct-acting alkylating agent, was given to p27 knock-out mice. Groups of 20-40 male and female mice with null, hetero- or wild-type p27 alleles were given drinking water containing 240 ppm MNU or distilled water every other week for five cycles. The incidence and multiplicity of the induced proliferative lesions were then histologically evaluated at weeks 14 and 20. MNU treatment induced various lesions including squamous hyperplasia and squamous cell carcinoma in the forestomach, atypical hyperplasia and adenocarcinomas in the fundic and pyloric glands, adenomas and adenocarcinomas in the duodenum, malignant lymphomas in the thymus, liver, kidney and spleen and alveolar hyperplasia, adenomas, adenocarcinomas and malignant lymphomas in the lung. Although the incidences of the lesions in the forestomach, fundic and pyloric glands did not differ among the p27 genotypes, those of alveolar hyperplasia of the lung and malignant lymphoma of the thymus were significantly increased in p27-null males as compared with both wild- and hetero-type animals. Moreover, in both p27(+/+) and p27(+/-) cases, the rates for p27-positive cells were obviously increased in proliferative lesions of the pyloric gland and the lung. However, an increased rate of p27-positive cells was not observed in malignant lymphoma of the thymus. These findings suggest that p27 does not control the cell cycle equally in all organs affected by MNU-induced carcinogenesis.

Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) as an antiinflammatory target: discovery and in vivo activity of selective pyrazolo[1,5-a]pyrimidine inhibitors using a focused library and structure-based optimization approach.

A novel class of mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) inhibitors was discovered through screening a kinase-focused library. A homology model of MAPKAP-K2 was generated and used to guide the initial SAR studies and to rationalize the observed selectivity over CDK2. An X-ray crystal structure of a compound from the active series bound to crystalline MAPKAP-K2 confirmed the predicted binding mode. This has enabled the discovery of a series of pyrazolo[1,5-a]pyrimidine derivatives showing good in vitro cellular potency as anti-TNF-α agents and in vivo efficacy in a mouse model of endotoxin shock.

Suppression of prostate cancer in a transgenic rat model via gamma-tocopherol activation of caspase signaling.

BACKGROUND: Epidemiological data indicate that intake of one form of vitamin E, gamma-tocopherol, may reduce prostate cancer risk, and several in vitro studies have demonstrated that gamma-tocopherol can inhibit prostate cancer cell growth. The purpose of the present study was to confirm effects of gamma-tocopherol on prostate cancer in the transgenic rat for adenocarcinoma of prostate (TRAP) model established in our laboratory. METHODS: In Experiment 1, heterozygous male TRAP rats 5 weeks of age received alpha-tocopherol at the concentration of 50 mg/kg in the diet, or gamma-tocopherol at 50 or 100 mg/kg for 10 weeks. In Experiment 2, TRAP rats of 3 weeks of age were given gamma-tocopherol at 50, 100, or 200 mg/kg diet for 7 weeks. RESULTS: gamma-Tocopherol did not affect body weight gain, organ weights or serum levels of either testosterone or estradiol. However, quantitative evaluation of prostatic lesions demonstrated significantly suppression of sequential progression from PIN to adenocarcinoma in a dose-dependent manner, along with clear activation of caspases 3 and 7 in the ventral lobe in both experiments. CONCLUSIONS: The present study clearly demonstrated that gamma-tocopherol suppresses prostate tumor progression in an in vivo TRAP model, and could be a candidate chemopreventive agent for human prostate cancer.

Suppression of prostate cancer growth by resveratrol in the transgenic rat for adenocarcinoma of prostate (TRAP) model.

Research into actions of resveratrol, abundantly present in red grape skin, has been greatly stimulated by its reported beneficial health influence. Since it was recently proposed as a potential prostate cancer chemopreventive agent, we here performed an in vivo experiment to explore its effect in the Transgenic Rat for Adenocarcinoma of Prostate (TRAP) model, featuring the rat probasin promoter/SV 40 T antigen. Resveratrol suppressed prostate cancer growth and induction of apoptosis through androgen receptor (AR) down-regulation, without any sign of toxicity. Resveratrol not only downregulated androgen receptor (AR) expression but also suppressed the androgen responsive glandular kallikrein 11 (Gk11), known to be an ortholog of the human prostate specific antigen (PSA), at the mRNA level. The data provide a mechanistic basis for resveratrol chemopreventive efficacy against prostate cancer.

Susceptibility of p27 kip1 knockout mice to urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine may not simply be due to enhanced proliferation.

Deregulated proliferation is one of the fundamental characteristics of carcinogenesis. p27 is one of the most well characterized negative cell cycle regulator. In our previous study, expression of p27 protein was found to be dramatically suppressed on stimulation of cell proliferation by calculi in the rodent urinary bladder, withdrawal of the insult resulting in re-expression of p27 and regression of urothelial hyperplastic lesions. In the present study, to evaluate how loss of function impacts on urinary bladder carcinogenesis, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), a bladder carcinogen was given to p27 knockout mice. Males and females with either null, hetero or wild-type p27 alleles were divided into 2 groups, one given drinking water containing 0.05% BBN for 10 weeks and the other receiving distilled water, then, killed at week 20. The experiment was repeated for confirmation of the outcome. In the second experiment, performed with a larger number of animals, the incidence of urinary bladder carcinomas was significantly higher in female p27-null mice than in their wild-type counterparts. p27 deficiency also resulted in their increase of relative weights of urinary bladders and section areas of carcinomas in BBN-treated mice. Interestingly, while BrdU labeling indices generally increased with progression of mucosal proliferative lesions, from normal epithelium, through hyperplasia to carcinoma, there was no significant variation with the p27 genotype, in tumors as well as normal urothelium. These findings suggest that p27 deficient mice have elevated susceptibility to BBN-induction of urinary bladder carcinogenesis through a mechanism which might be independent of acceleration of cell cycling.

[Concurrent chemoradiation therapy for advanced cervical cancer].

In 2003, we began a clinical application of concurrent chemoradiation therapy (CCR) in patients with cervical cancer in our hospital. We analyzed 14 cases of advanced cervical cancer in stages IIa through IIIb by FIGO classification. Tumor size of the uterine cervix ranged from 1.5 cm to 8.0 cm in diameter. Patients received radiation therapy (50 Gy of external beam radiotherapy for pelvis and 20 Gy of high-dose rate intracavitary brachytherapy) combined with chemotherapy. Cisplatin was administered intravenously every 3 weeks at a dose of 70 mg/m(2) during the radiation therapy. In two cases, CCR was stopped because of the side effects. One case developed acute renal failure and another suffered intolerable exhaustion. As for the antitumor effects of CCR, the response rate was 75% (CR 58.3%,PR 16.7%). At the end of the CCR, 10 of 12 patients (83.3%) were negative for viable cells by cytology or biopsy of the uterine cervix. The grade 3 adverse effects were leukopenia, diarrhea and anemia. There was no statistical difference in the overall survival between CCR and radiation therapy alone. The CCR response rate in patients with paraaortic lymph node swelling (suspected metastasis) was low, and they had a poor prognosis. Further examinations for the long-term survival benefit of CCR are necessary.

Preoperative identification of subthalamic nucleus for deep brain stimulation using three-dimensional phase sensitive inversion recovery technique.

PURPOSE: We assessed the feasibility of utilizing three-dimensional (3D) phase sensitive inversion recovery (IR) images for preoperatively determining deep brain stimulator position. METHODS: We measured geometric distortion with a grid phantom and evaluated images of 3 volunteers to determine optimum imaging parameters for 3D phase sensitive IR. RESULTS: Geometric distortion measured less than 1.0%. Respective inversion and recovery times, which provided high T(1) contrast between the subthalamic nucleus and adjacent tissue, were 200 and 4000 ms. In studies of 3 volunteers and 2 patients, the subthalamic nucleus was clearly depicted in 3D phase sensitive IR images. The measured coordinates of the subthalamic nucleus agreed well with those calculated by conventional estimation from midpoint of the anterior and posterior commissure. CONCLUSION: Three-dimensional phase sensitive inversion recovery was useful in visualizing the subthalamic nucleus for effective deep brain stimulation.

Peripheral MR angiography: separation of arteries from veins with flow-spoiled gradient pulses in electrocardiography-triggered three-dimensional half-Fourier fast spin-echo imaging.

The authors evaluated a nonenhanced magnetic resonance (MR) angiographic technique that allows separation of arteries from veins. In 15 healthy subjects, peripheral MR angiography was performed with readout flow-spoiled gradient pulses in electrocardiography-triggered three-dimensional half-Fourier fast spin-echo MR imaging. Appropriate flow-spoiled gradient pulses were measured and applied in the three-dimensional acquisition to differentiate arteries and veins in the peripheral vasculature. Subtraction of the diastolic bright-blood arteries from the systolic black-blood arteries allowed visualization of the arteries by cancelling the veins, which are constantly depicted as bright blood throughout the cardiac cycle. Stronger flow-spoiled gradient pulses improved the depiction of slow-flow arteries even in the distal foot and hand vessels.

Reversibility of proliferative lesions and induction of non-papillary tumors in rat urinary bladder treated with phenylethyl isothiocyanate.

Phenylethyl isothiocyanate (PEITC), generally thought to be a chemopreventive agent for various kinds of genotoxic carcinogens, has been found to induce rat urinary bladder carcinomas in our laboratory. To cast light on the underlying mechanisms, the reversibility of urothelial proliferative lesions and the frequencies of H-ras and p53 mutations in the induced rat urinary bladder tumors were investigated. F344 male rats were given diet containing 0.1% PEITC for 48 weeks and then killed, or for 32 weeks and then returned to normal diet without supplement for 1, 3, 7 days or 16 weeks before death. At 7 days after withdrawal of PEITC treatment, carcinomas were observed in only two of 24 rats but a high incidence of dysplasias was evident. Furthermore, 16 weeks after withdrawal, seven of 12 (58.3%) rats had carcinomas. In addition, carcinomas were induced in 11 of 12 (91.7%) rats continuously receiving PEITC for 48 weeks. Most of the carcinomas were characterized as of non-papillary transitional cell type with occasional squamous cell differentiation and/or glandular components. Bromodeoxyuridine labeling indices (LIs) were increased by PEITC administration even in normal-looking epithelium. After withdrawal of treatment, LIs in simple and papillary or nodular (PN) hyperplasias were markedly decreased and these lesions gradually disappeared, while values for dysplasias and carcinomas, which persisted, were only slightly decreased. A silent point mutation was found in H-ras in one of 12 tumor samples (8.3%), whereas seven (58.3%) had mutations in p53. These results indicate that PEITC itself is a carcinogen for the rat urinary bladder, and that while the simple and PN hyperplasia induced by PEITC are reversible, dysplasia is irreversible with the potential to give rise to non-papillary carcinomas with frequent p53 mutations.

Virtual endoscopic images by 3D FASE cisternography for neurovascular compression.

Three-dimensional fast asymmetric spin echo (3D FASE) cisternography provides high spatial resolution and excellent contrast as a water image acquisition technique. It is also useful for the evaluation of various anatomical regions. This study investigated the usefulness and limitations of virtual endoscopic images obtained by 3D FASE MR cisternography in the preoperative evaluation of patients with neurovascular compression. The study included 12 patients with neurovascular compression: 10 with hemifacial spasm and two with trigeminal neuralgia. The diagnosis was surgically confirmed in all patients. The virtual endoscopic images obtained were judged to be of acceptable quality for interpretation in all cases. The areas of compression identified in preoperative diagnosis with virtual endoscopic images showed good agreement with those observed from surgery, except in one case in which the common trunk of the anterior inferior cerebellar artery and posterior inferior cerebellar artery (AICA-PICA) bifurcated near the root exit zone of the facial nerve. The veins are displayed in some cases but not in others. The main advantage of generating virtual endoscopic images is that such images can be used for surgical simulation, allowing the neurosurgeon to perform surgical procedures with greater confidence.

Flow-weighted MRI of the lungs with the ECG-gated half-Fourier FSE technique: evaluation of the effect of the cardiac cycle.

We investigated temporal MR signal changes in the peripheral lung and proximal pulmonary vessels during the entire cardiac cycle in order to evaluate the characteristics of the diastolic-systolic subtraction method in the lung. In eight healthy volunteers free of lung diseases, changes in the MR signal during one breath-hold were investigated with the multiple ECG-triggered half-Fourier single-shot fast-spin echo (SS-FSE) technique. The signal intensity-time course curve in the lung showed that biphasic signals decreased 20% to 47% at systole and 5% to 33% at mid-diastole, measured against the maximum signals at late diastole. This signal decrease in the peripheral lung was correlated to that in the proximal pulmonary vessels during an entire cardiac cycle (r=0.667 to 1.000). The best visualization of the lung was obtained at late diastole, when the intra-vascular flow in the lung was expected to be stagnant. Compared with the late diastolic SS-FSE images, the late diastolic-systolic subtracted SS-FSE images improved the signal-to-noise ratio in the lung as well as the signal-intensity ratio of the peripheral lung to surrounding tissues. Although the flow-induced signal dephasing in the lung was completely unavoidable and its amount was unpredictable even at late diastole, the diastolic-systolic subtracted SS-FSE images showed the relative differences in flow alteration during the cardiac cycle between the images at diastole and those at systole. The main characteristic of diastolic-systolic subtracted SS-FSE was the enhancement of visibility of cardiac-dependent signal changes in the lung due to the alteration in pulsatile flow.