Cost utility analysis of pharmacist counseling care for breast cancer chemotherapy outpatients.

Chemotherapy for cancer is increasingly implemented in the outpatient setting. Pharmacists contribute to cancer treatment by conducting counseling during outpatient chemotherapy visits. They provide guidance on drug treatment, side effects, and side effect countermeasures on every visit. However, there have been few economic evaluations of pharmacist involvement in outpatient chemotherapy. Therefore, we performed a cost utility analysis. We assigned usual care (control) and pharmacist counseling to two groups of 19 patients receiving outpatient chemotherapy for breast cancer at Gifu Municipal hospital. Quality of life was measured at three timepoints before and during chemotherapy treatment using the EuroQol 5 dimension instrument (EQ-5D). EQ-5D values across the timepoints were 0.831, 0.757, and 0.791 for the control group, and 0.882, 0.883, and 0.921 for the pharmacist counseling group. The additional cost in the pharmacist counseling group was 2,227 yen per counseling session. The change in quality-adjusted life years (QALY) was a maximum of -0.021±0.186 in the control group and 0.007±0.199 in the pharmacist counseling group. The maximum cost for one QALY was 1,360,558 yen (≈12,460 US dollars). Pharmacists' counseling in outpatient cancer chemotherapy for breast cancer patients had an acceptable incremental cost-effect ratio, contributing to improved patient quality of life without significant additional expenditure to healthcare.

The TriAGe+ Score for Vertigo or Dizziness: A Diagnostic Model for Stroke in the Emergency Department.

BACKGROUND: Vertigo or dizziness is a common occurrence, but it remains a challenging symptom when encountered in the emergency department (ED). A diagnostic score for stroke with high accuracy is therefore required. METHODS: A single-center observational study (498 patients) was conducted. The predictor variables were derived from a multivariate logistic regression analysis with Akaike information criterion. The outcome was the occurrence of stroke. We evaluated the utility of a new diagnostic score (TriAGe+) and compared it with the ABCD2 score. RESULTS: The cohorts included 498 patients (147 with stroke [29.4%]). Eight variables were included: triggers, atrial fibrillation, male gender, blood pressure ≥140/90 mm Hg, brainstem or cerebellar dysfunction, focal weakness or speech impairment, dizziness, and no history of vertigo or dizziness or labyrinth or vestibular disease. We derived the TriAGe+ score from these variables. In the cohort, the prevalence of stroke increased significantly using the diagnostic score: 5.9% for a score of 0-4; 9.1% for 5-7; 24.7% for 8-9; and 57.3% for 10-17. At a cutoff value of 10 points, the sensitivity of the score was 77.5%, the specificity was 72.1%, and the positive likelihood ratio was 3.2. When the cutoff was defined as 5 points, the score obtained a high sensitivity (96.6%) with a good negative likelihood ratio (.15). The new score outperformed the ABCD2 score for the occurrence of stroke (C statistic, .818 versus .726; P < .001). CONCLUSIONS: The TriAGe+ score can identify the occurrence of stroke in patients with vertigo or dizziness presenting to the ED.

Effects of fatigue from sleep deprivation on experimental periodontitis in rats.

BACKGROUND AND OBJECTIVE: Factors such as vascularization of the periodontium, inflammatory reactions and immune response affect the oral environment and ecology, decreasing host resistance and promoting the development of symptoms and the advancement of periodontal disease. Fatigue also influences the hypothalamic-pituitary-adrenal axis and reports relate it to systemic resistance. The aim of this study was to evaluate whether fatigue is a modifying factor for periodontal disease in rats. MATERIAL AND METHODS: We divided 24 3-wk-old male Sprague-Dawley rats randomly into the following four groups: control; fatigue (deep sleep deprivation for 7 d); infection (rats inoculated with carboxymethyl cellulose containing periodontopathic bacteria); and compound (combined fatigue and infection conditions). Weight, serum corticosterone levels, serum albumin levels, interleukin-1ß and tumor necrosis factor-α expression levels and distance from the cement-enamel junction to the alveolar bone crest were measured at baseline, and on the 36th (before sleep deprivation), 43rd (immediately after sleep deprivation) and 57th d (end of experiment). RESULTS: Immediately after sleep deprivation and at the end of the experiment, weight gain in the fatigue and compound groups was significantly lower than in controls (p < 0.05). Immediately after sleep deprivation, serum corticosterone levels were significantly higher in the fatigue and compound groups than in controls (p < 0.05). Moreover, serum albumin levels were significantly lower in the fatigue and compound groups than in controls (p < 0.05). Immediately after sleep deprivation, gene expression of interleukin-1ß was significantly higher in the infection and compound groups than in controls (p < 0.05). Moreover, gene expression of tumor necrosis factor-α was significantly higher in the compound group than in controls (p < 0.05). At the end of the experiment, the distance from the cement-enamel junction to the alveolar bone crest was significantly higher in the infection and compound groups than in controls (p < 0.05). Moreover, the distance was significantly higher in the compound group than in the infection group. CONCLUSIONS: Fatigue worsened systemic health in rats and increased gingival inflammation and alveolar bone loss in experimental periodontitis. In conclusion, our results suggest that fatigue is a modifying factor for periodontal disease in rats.

Utility of patch testing for patients with drug eruption.

BACKGROUND: Patch testing is less dangerous than oral provocation testing for identification of the causative drug for patients with drug eruption; however, its usefulness for such identification is controversial. AIM: To clarify the rates of positive patch testing for patients with drug eruption, classified by causative drugs and clinical features. METHODS: We analysed results during the period 1990-2010 for 444 patients (151 men, 293 women; mean ± SD age 49.9 ± 18.6 years) who were tested for drug eruption. In the patient group, there were 309 people (69.1%) with maculopapular eruption and 31 (6.9%) with severe drug eruption. The test materials were applied to the back and left for 2 days under occlusion, then results were assessed by the International Contact Dermatitis Research Group (ICDRG) scoring system 3 days after application. Reactions of + to +++ were regarded as positive. RESULTS: Of the 444 patients, 100 (22.4%) had a positive patch test result to a suspected drug. Positive rates were 23.6% and 20.0% for maculopapular eruption and fixed drug eruption, respectively. The class of materials to which most patients reacted positively was contrast medium (n = 53; 41.1%), followed by drugs acting on the central nervous system (n = 18; 28.6%). In the latter group, 16 of the 18 patients were positive to antiepileptics. CONCLUSIONS: Positive rates depend on the causative drug rather than the clinical features of the drug eruption. Patch testing is useful when contrast medium or antiepileptics are suspected to be the causative drugs. However, standardization of patch test materials and method of reading is needed, as well as guidelines regarding when testing should be performed. Although patch testing for drug eruption has significant potential, it requires further validation.

Limit on neutrinoless ßß decay of 136Xe from the first phase of KamLAND-Zen and comparison with the positive claim in 76Ge.

We present results from the first phase of the KamLAND-Zen double-beta decay experiment, corresponding to an exposure of 89.5 kg yr of (136)Xe. We obtain a lower limit for the neutrinoless double-beta decay half-life of T(1/2)(0ν)>1.9×10(25) yr at 90% C.L. The combined results from KamLAND-Zen and EXO-200 give T(1/2)(0ν)>3.4×10(25) yr at 90% C.L., which corresponds to a Majorana neutrino mass limit of <(120-250) meV based on a representative range of available matrix element calculations. Using those calculations, this result excludes the Majorana neutrino mass range expected from the neutrinoless double-beta decay detection claim in (76)Ge, reported by a part of the Heidelberg-Moscow Collaboration, at more than 97.5% C.L.

Acrosome reaction of fowl sperm: evidence for shedding of the acrosomal cap in intact form to release acrosomal enzyme.

The aim of this study was to determine the site of enzyme release from the acrosome and the fate of the acrosomal cap during the process of acrosome reaction (AR) in fowl sperm. Gelatin substrate coverslips with halos were subjected to scanning electron microscopy to determine the site from which acrosomal proteolytic enzyme was released to form a halo around the acrosome of individual sperm. Aliquots of sperm treated with solubilized inner perivitelline layer (IPL) containing 5 mmol CaCl(2) were simultaneously subjected to fluorescent staining with fluorescein isothiocyanate-labeled peanut agglutinin and scanning electron microscopy to evaluate AR of sperm and to examine the status of the acrosomal region, respectively. Inside the halos, a gelatin-free (proteolyzed gelatin) layer was found extending some distance around the acrosome of sperm. All of the sperm showing the formation of halos on gelatin had a single circular opening around their subacrosomal rod at the base of the acrosomal cap. Interaction of sperm with solubilized IPL in the presence of 5 mmol CaCl(2) resulted in 41.4 ± 1.8% of the sperm to undergo AR, as evaluated by fluorescein isothiocyanate-labeled peanut agglutinin. Similarly, as observed using scanning electron microscopy, 38.2 ± 2.3% of the sperm treated with solubilized IPL plus 5 mmol CaCl(2) had exposed subacrosomal rod. In all sperm examined, no sign of disruption of the acrosomal membrane was found in the apical region of the acrosome. Rather, the acrosomal caps were found intact detached from the acrosomal region of the sperm, indicating that AR of fowl sperm resulted in the intact removal of the acrosomal cap. Based on these experimental observations, we suggest that the process of AR in fowl sperm is unique; the release of the acrosomal proteolytic enzyme may occur through a single circular opening formed at the base of the acrosomal cap and the acrosomal cap is detached in intact form from the posterior acrosomal region of the sperm.

Plumping fluid added to storage medium increases twofold the functional life span of fowl spermatozoa in vitro at 4°C.

1. The objective of this study was to examine whether addition of plumping fluid (PF) to Lake's solution (LS) for storage of fowl spermatozoa in vitro at 4°C can prolong survival and improve the quality of spermatozoa. 2. In experiment 1, aliquots of spermatozoa were stored in vitro in LS alone and LS containing 10%, 25%, 50% and 75% (v:v) PF for 0.5, 24, 48, 72, 96 and 120 h at 4°C. After the end of each storage period, spermatozoa were evaluated for their viability, mobility and penetrability. Viability was determined using SYBR-14 and propidium iodide (PI) staining. Mobility was assessed using an Accudenz assay. Penetrability was assessed using spermatozoa-inner perivitelline layer (IPL) interaction assay. 3. In experiment 2, aliquots of spermatozoa were stored in vitro in LS alone and LS containing 25% and 50% (v:v) PF for 0.5, 24, 48 and 72 h at 4°C, and then fertility of the spermatozoa was evaluated using intravaginal artificial insemination (AI) in hens. 4. Storage of spermatozoa in LS alone resulted in loss of viability, mobility, penetrability and fertility within 48 h. In contrast, no loss of viability and penetrability was observed for the spermatozoa stored for 48, 96, 72 and 48 h in LS containing 10%, 25%, 50% and 75% (v:v) PF, respectively. In particular, fertilising capacity was not lost for the spermatozoa stored in the presence of 25% or 50% PF in LS for 48 and 24 h, respectively. 5. In conclusion, these findings demonstrated that in vitro exposure of fowl spermatozoa to PF during hypothermic storage in LS prolonged spermatozoa survival. A 25% (v:v) level of inclusion of PF in LS may be effective for the improvement of viability, penetrability and fertilising ability of the stored spermatozoa.

Inhibition of human colon cancer growth by antibody-directed human LAK cells in SCID mice.

Advanced human colon cancer does not respond to lymphokine-activated killer (LAK) cells. In order to direct cytotoxic cells to the tumor, human LAK cells linked with antibodies to a tumor cell surface antigen were tested with established hepatic metastases in severe combined immunodeficient (SCID) mice. These cells had increased uptake into the tumor and suppression of tumor growth as compared with LAK cells alone, thereby improving the survival of tumor-bearing mice. Thus, tumor growth can be inhibited by targeted LAK cells, and SCID mice can be used to test the antitumor properties of human effector cells.

A support system for context awareness in a group home using sound cues.

OBJECTIVES: In a group home, caregivers should be aware of the inhabitant's real-time situation. The aim of our study is to facilitate the awareness of an inhabitant's situation by means of enhanced sound cues. METHODS: We propose an audio notification system that indicates the real-time situation of persons in a group home environment using sound cues instead of visual surveillance. The notification system comprises a prediction and a notification function. The prediction function estimates a person's real-time situation using a Bayesian network and sensed information; the notification function informs recipients of the predicted situation and the confidence level of the prediction by means of sound cues. We use natural sounds as sound cues. RESULTS: As a first step to examine our system in a group home, we conducted operation and performance tests of each unit under a simple test environment. The correct prediction of the subject's situation is approximately 90%; further, it is shown that the sound cues should be selected according to their environmental dependence. CONCLUSIONS: The results show that the method is useful for monitoring persons. As future study, we will conduct a field test on an implemented system and improve it for practical use in a group home.

Evaluation of post-procedure changes in aneurysmal lumen following detachable coil-placement using multi-planar reconstruction of high-field (3.0T) magnetic resonance angiography.

BACKGROUND: Placement of detachable coil(s) for intracranial aneurysms has become one of the standard methods of management. Although detailed analysis of post-procedure changes in aneurysmal lumen is essential, technical difficulties often limit such evaluation. Development of higher magnetic field systems is steadily widening clinical usage of magnetic resonance imaging (MRI) primarily due to its significantly higher signal to noise ratio. OBJECTIVE: In this study, we evaluated a multi-planar reconstruction (MPR) technique of magnetic resonance angiography (MRA) on a 3.0T system in an attempt to develop a routine method of post-procedure evaluation following detachable coil placement. METHODS: Eleven patients with an intracranial aneurysm following placement of a Guglielmi detachable coil (GDC) participated in the study. Time of flight (TOF) magnetic resonance angiography (MRA) was obtained immediately after, and up to two years after coil embolisation utilising a GE 3.0T system. Data was analysed using standard maximum intensity projection (MIP) as well as the MPR technique and the results were compared to conventional catheter angiography. RESULTS: The study demonstrated that, compared to MIP, MPR can provide further information of alteration in aneurysm lumen, especially in analysis of: 1) jet of blood flow, 2) thrombus formation, 3) neck remnant or re-filling of blood, 4) location and shape of coils including compaction, and 5) coil protrusion into the parent artery. CONCLUSIONS: Combined MPR/MIP analysis of high-field MRA appears to be a powerful non-invasive method for evaluating GDC-treatment that can potentially replace conventional catheter angiography in many clinical situations.

Novel responses of peripheral lymphocytes of cancer patients to chemical induction of sister chromatid exchanges.

Sensitivities to sister chromatid exchange (SCE) induction by chemicals of peripheral lymphocytes from 26 cancer patients were estimated under conditions identical to those for healthy humans which had been reported (Cancer Res., 43: 439-442, 1983). The sensitive individual was defined as one whose cells give a mean induced SCE frequency more than 2 standard deviation units above the population mean of induced SCEs in cells from the healthy humans. When cells were treated with 3-amino-1-methyl-5H-pyrido[4, 3-b]indole in the presence of rat liver S9 mix, 8 in 10 stomach cancer patients, 4 in 4 colon cancer patients, 3 in 9 lung cancer patients, 0 in 3 patients bearing other cancers, and 0 in 9 non-cancerous individuals were sensitive. The corresponding frequency of individuals in the healthy population, reported previously, was 1 in 33 persons. Thus, the frequency of sensitive individuals in the combined group of stomach and colon cancer patients was very significantly higher than were frequencies in control groups. Three in 10 patients with stomach cancer and 4 in 16 patients with other cancers were sensitive to induction of SCE by methyl methanesulfonate. Six in these 7 methyl methanesulfonate-sensitive patients were also 3-amino-1-methyl-5H-pyrido[4,3-b]indole sensitive. The frequency of methyl methanesulfonate-sensitive individuals in the healthy populations was 2 in 50. There was no patient who was sensitive to SCE induction by 4-nitroquinoline 1-oxide. The frequency was not significantly different from the healthy population, in which 3 in 50 persons were sensitive. These results suggest that a particular cancer correlates with the sensitivity of peripheral lymphocytes to SCE induction by particular chemicals.

Quantitative Analyses of Hepatic OATP-Mediated Interactions Between Statins and Inhibitors Using PBPK Modeling With a Parameter Optimization Method.

This study aimed to construct a widely applicable method for quantitative analyses of drug-drug interactions (DDIs) caused by the inhibition of hepatic organic anion transporting polypeptides (OATPs) using physiologically based pharmacokinetic (PBPK) modeling. Models were constructed for pitavastatin, fluvastatin, and pravastatin as substrates and cyclosporin A (CsA) and rifampicin (RIF) as inhibitors, where enterohepatic circulations (EHC) of statins were incorporated. By fitting to clinical data, parameters that described absorption, hepatic elimination, and EHC processes were optimized, and the extent of these DDIs was explained satisfactorily. Similar in vivo inhibition constant (Ki ) values of each inhibitor against OATPs were obtained, regardless of the substrates. Estimated Ki values of CsA were comparable to reported in vitro values with the preincubation of CsA, while those of RIF were smaller than reported in vitro values (coincubation). In conclusion, this study proposes a method to optimize in vivo PBPK parameters in hepatic uptake transporter-mediated DDIs.

Cloning and sequencing of trehalose biosynthesis genes from Arthrobacter sp. Q36.

A 5.1-kbp genomic DNA fragment was cloned from trehalose-producing bacterium Arthrobacter sp. strain Q36. Sequence analysis of the DNA fragment revealed two open reading frames of 2325 and 1794 bp, encoding maltooligosyltrehalose synthase (TreY) and maltooligosyltrehalose trehalohydrolase (TreZ), respectively. The 3' end of treY overlaps with the 5' end of treZ by one nucleotide, and it is suggested that treYZ constitutes and operon. The deduced amino acid sequences of both enzymes have several regions common to amylolytic enzymes belonging to an 'alpha-amylase family'.

Cloning and sequencing of a cluster of genes encoding novel enzymes of trehalose biosynthesis from thermophilic archaebacterium Sulfolobus acidocaldarius.

Trehalose biosynthesis genes, treZ, treX and treY, encoding maltooligosyltrehalose trehalohydrolase (TreZ), glycogen debranching enzyme (TreX), and maltooligosyltrehalose synthase (TreY) have been cloned from the thermophilic archaebacterium Sulfolobus acidocaldarius ATCC33909. The amino-acid sequences deduced from treZ, treX and treY are composed of 556, 713 and 720 amino-acid residues, respectively. TreZ and TreY are 33-40% homologous to the corresponding enzymes from Arthrobacter sp. Q36. We have proposed that the biosynthesis of trehalose in Sulfolobus occurs via the actions of the three enzymes encoded by treZXY.

Cloning and sequencing of trehalose synthase gene from Thermus aquaticus ATCC33923.

The gene encoding trehalose synthase (catalyzing the conversion of maltose into alpha, alpha-trehalose by transglucosylation) was cloned from Thermus aquaticus ATCC33923. Sequence analysis revealed a 2892 bp synthase gene and a 963 residue amino-acid sequence. The 547 N-terminal residues were homologous to the full-length synthase from Pimelobacter sp. R48 (53.8% identity).

Cloning and sequencing of trehalose synthase gene from Pimelobacter sp. R48.

The gene encoding trehalose synthase (catalyzing the conversion of maltose into alpha, alpha-trehalose by intramolecular transglucosylation) was cloned from Pimelobacter sp. R48. Sequence analysis revealed a 1719-bp synthase gene and a 573-residue amino-acid sequence. The 220 N-terminal residues were homologous to those of maltases from Saccharomyces carlsbergensis and Aedes aegypti.

Chewing oscillopsia. A case of voluntary visual illusions of movement.

A 60-year-old man had a history of frontal headaches and chewing-related oscillopsia. Examination disclosed a retro-orbital epidermoid cyst that had eroded through the lateral orbital wall and under the temporalis muscle. The illusion of movement was due to mechanical displacement of the tumor mass and eye by contraction of the temporalis muscle. Removal of the cyst produced complete remission of the oscillopsia.