Community pharmacy-level factors associated with medical and nursing home facility collaboration in Japan.

The aim of this study was to clarify the community pharmacy-level factors related to experiences of and attitudes toward collaboration with medical and nursing home care facilities. We conducted a postal questionnaire survey of all pharmacies in Gifu, Japan, assessing the experiences and attitudes of supervising pharmacists regarding the following activities related to collaboration between medical facilities and nursing home care facilities: regional care meetings/service adjustment meetings, case discussion conferences, joint workshops/continuing education conferences, community service, information sharing through medical cooperation networks, and pharmacists accompanying physicians on home care visits. The factors significantly related to inter-professional collaboration were the family pharmacist guidance fee and the number of patients offered pharmaceutical care through cooperation with other medical facilities. Items on attitudes toward collaborating with other medical facilities showed similar results. Overall, policies that support inter-professional collaboration to create a foundation, establish mechanisms to facilitate collaboration, and identify collaborative activities that can be carried out at each pharmacy should be developed.

Finasteride 1 mg has no inhibitory effect on omeprazole metabolism in extensive and poor metabolizers for CYP2C19 in Japanese.

OBJECTIVE: To examine the inhibitory effect of finasteride 1 mg on the metabolism of omeprazole in genetically determined extensive (EMs) and poor metabolizers (PMs) for CYP2C19 in young healthy Japanese male subjects. METHODS: Twenty-four volunteers participated in this study, among whom 12 were homozygous EMs and 12 were PMs for CYP2C19. A single center, controlled, randomized, open, crossover study with a 5 day washout between the two study periods was performed. Each of the six EMs and PMs received a single oral 20 mg dose of omeprazole on day 1 (treatment I). After a 5 day washout period, these subjects received 1 mg of finasteride once a day for three consecutive days, and a single oral 20 mg dose of omeprazole was co-administered on day 3 (treatment II). The 12 other EMs and PMs received treatments I and II in reverse. Plasma samples were collected for up to a 12 hours postdose of omeprazole, and the pharmacokinetic parameters of omeprazole were determined. RESULTS: The geometric mean ratio (GMR) for the AUC((0-12 hr)) of omeprazole when co-administered with finasteride/omeprazole alone is 1.13 (90%CI, 1.03, 1.25) and 0.96 (0.88, 1.05) in EMs and PMs, respectively. Finasteride did not significantly alter C(max), T(max) and t(1/2) in both genotypes. CONCLUSION: Finasteride 1 mg, widely used for the treatment of androgenetic alopecia in men, did not meaningfully increase omeprazole exposure (20 mg) in both EMs and PMs for CYP2C19. These results indicate that finasteride does not meaningfully inhibit CYP2C19 activity in vivo at the dose of 1 mg.

pH-sensing nano-crystals of carbonate apatite: effects on intracellular delivery and release of DNA for efficient expression into mammalian cells.

Two unique and fascinating properties of carbonate apatite which are well-known in hard tissue engineering, have been unveiled, for the first time, for the development of the simplest, but most efficient non-viral gene delivery device - ability of preventing the growth of crystals needed for high frequency DNA transfer across a plasma membrane and a fast dissolution rate for effective release of DNA during endosomal acidification, leading to a remarkably high transgene expression (5 to 100-fold) in mammalian cells compared to the widely used transfecting agents. Moreover, by modulating the crystal dissolution rate of carbonate apatite through incorporation of fluoride or strontium into it, transfection activity could be dramatically controlled, thus shedding light on a new barrier in the non-viral route, which was overlooked so far. Thus we have developed an innovative technology with significant insights, that would come as a promising tool for both basic research laboratories and clinical settings.

Immunolocalization of centriole-associated striated rootlets in human submandibular gland cells with and without solitary cilia.

Using an antibody specific to striated rootlets, we investigated the immuolocalization of striated rootlets in cells constituting human submandibular glands. Striated rootlets were positively stained in all cell types constituting acini, intercalated ducts, striated ducts, and interlobular ducts, but their shapes were different. The mean lengths of striated rootlets were 1.46 +/- 0.49, 3.15 +/- 1.35 and 3.99 +/- 1.02 microm in acinar secretory cells, myoepithelial cells, and columnar cells of the striated duct, respectively. The rootlets were the longest in columnar cells of the striated duct, in which paired centrioles were located in the apical cytoplasm away from nuclei. These findings suggest that striated rootlets play important roles in the positioning of centrioles in the cell. 2-8% of striated rootlets in myoepithelial cells were associated with solitary cilia, but they were not associated with solitary cilia in acinar cells and columnar cells of the striated duct. These observations suggest that striated rootlets may be associated with centrioles under normal physiological conditions, without formation of solitary cilia.

Immunocytochemistry of the striated rootlets associated with solitary cilia in human oviductal secretory cells.

The human oviduct epithelium is a simple columnar structure that consists primarily of ciliated and secretory cells. Solitary cilia usually extend from the apical cell surface of secretory cells. By injecting crude preparations of striated rootlets into rats, we successfully obtained six monoclonal antibodies (R38, R67, R95, R149, R155, R213) that commonly labeled ciliary rootlets. Using these antibodies, proteins of 205-215 kDa were identified by immunoblotting. Using a clone, R67, we investigated the morphology of the striated rootlets associated with solitary cilia by immunocytochemistry. It was found that the shapes of the rootlets were not simple but varied considerably. The rootlets had branched, radiated, arched, and looped shapes. This is the first report of the rootlets having a variety of shapes. The 205- to 215-kDa antigens identified by the six different antibodies were mostly localized to dark bands of striations, suggesting that they are constitutive components of dark striations of the rootlet.

Localization of gamma-tubulin to the basal foot associated with the basal body extending a cilium.

The human oviduct epithelium primarily consists of ciliated cells and secretory cells. Solitary cilia usually extend from the apical surface of the secretory cells. We investigated the localization of gamma-tubulin in the ciliary basal apparatus of both cell types by fluorescence immunohistochemistry and immunoelectron microscopy. In addition to basal bodies, gamma-tubulin was identified in the lateral basal foot, especially the basal foot cap. This observation is consistent with previous observations that microtubules radiate from the basal foot and the basal foot serves as the microtubule organizing centre.

Preparation of dendritic graft copolymer consisting of poly-(L-lysine) and arabinogalactan as a hepatocyte specific DNA carrier.

The dendriTIc graft copolymers (PAX) consisting of a poly(L-lysine) (PLL) main chain and grafts of arabinogalactan (AG) were prepared as a liver cell-specific DNA carrier. The copolymers were successfully prepared by reductive amination reaction between a reductive end of AG and epsilon-amino groups of PLL using NaBH3CN as a catalyst. The fractionation of a low molecular weight fraction (Mn = 25 kDa) from a crude AG (Mn = 33 kDa) was essential for the reaction to proceed. The resulting copolymers were isolated by ultrafiltration from unreacted AG and characterized by 1H NMR and gel permeation chromatography equipped with a multiangle laser light scattering detector (GPC-MALLS). The binding and internalization of DNA to hepatoma cells, HepG2, were considerably enhanced by complexing DNA with PAX copolymers. The interactions between PAX/DNA complexes and HepG2 cells were thoroughly inhibited in the presence of a competitor to asialoglycoprotein receptors (ASGP-R), indicating high specificity of the complex to ASGP-R. Furthermore, the PAX copolymers allowed the expression of the reporter gene. Our results reveal that the PAX copolymers may provide a new research tool for cell-specific gene delivery and eventually enhance gene-therapy technology.

IRF-1 is an essential mediator in IFN-gamma-induced cell cycle arrest and apoptosis of primary cultured hepatocytes.

IFN-gamma induces cell cycle arrest and p53-independent apoptosis in primary cultured hepatocytes. However, it is not yet understood what molecules regulate the mechanism. We report here that interferon regulatory factor 1 (IRF-1) is an essential molecule in these phenomena. Hepatocytes from IRF-1-deficient mice were completely resistant to IFN-gamma in apoptosis indicated by three different hallmarks such as LDH release, DNA fragmentation and the activation of caspase-3 family. Caspase-1 expression was little detected in hepatocytes, and constitutive and IFN-gamma-induced mRNA expression of Fas or caspase-3 did not change in between wild type and IRF-1-deficient hepatocytes. Expression of IFN-gamma-inducible caspase, caspase-11, did not change either. Thus, it is unlikely that these molecules directly regulate the mechanisms. Interestingly, IRF-1-deficient hepatocytes were also resistant to IFN-gamma-induced cell cycle arrest despite IFN-gamma-induced cell cycle arrest and apoptosis are regulated by independent pathways. Results by Northern blot analysis showed that IFN-gamma-induced but not constitutive p53 mRNA expression was regulated by IRF-1. In fact, IFN-gamma did not induce cell cycle arrest in p53-deficient hepatocytes. Taken together, IRF-1 mediates IFN-gamma signaling into primary hepatocytes for cell cycle arrest via p53 expression and for apoptosis.

Analysis of IFN-gamma-induced cell cycle arrest and cell death in hepatocytes.

The mechanism by which IFN-gamma induces cell cycle arrest and cell death in primary cultured hepatocytes was examined. The cell death exhibits apoptotic characters such as the appearance of apoptotic bodies and DNA fragmentation. IFN-gamma induced cell cycle arrest at the initial stage, followed by cell death. A protein synthesis inhibitor, cycloheximide, significantly inhibited cell death, implying that IFN-gamma induces de novo proteins involved in the death of hepatocytes. One of the most important apoptosis-related proteins, p53, was induced by IFN-gamma in hepatocytes in a dose- and time-dependent manner. Northern blot analysis demonstrated that IFN-gamma enhanced p53 mRNA expression as well as p21(WAF1/Cip1/Sdi1) mRNA expression, which is mediated by the increased expression of the p53 protein. Interestingly, IFN-gamma also induced cell death in p53-deficient hepatocytes. The cell death occurred rather earlier in p53-deficient cells than in normal hepatocytes. However, the cell death was not accompanied by apoptotic bodies. Therefore, IFN-gamma-induced hepatocyte cell death is p53-independent, and p53 may contribute to the apoptotic characters. In conclusion, IFN-gamma is supposed to cause cell cycle arrest by inducing p53 and p21(WAF1/Cip1/Sdi1), and it was demonstrated that IFN-gamma induces p53-independent cell death in primary cultured hepatocytes.

Benign cementoblastoma. Case report.

Benign cementoblastoma is a rare benign odontogenic tumour of mesenchymal origin. A case of a 24-year-old man with benign cementoblastoma is presented. The lesion manifested as a round, radiopaque mass attached to the root of the left first molar of the mandible. The tooth was extracted and the lesion was removed. A diagnosis of benign cementoblastoma was made microscopically. There has been no evidence of recurrence during the three-year follow-up period. A review of the literature and a discussion of the histologic features of this case are included.

Effects of ventilation and pleural effusion on measurements of airway thermal volume and blood flow in dog lungs.

We studied the effects of ventilation and pleural effusion on measurements of airway thermal volume (ATV) and pulmonary blood flow (PBF) by using the airway gas thermometry method of V. B. Serikov, M. S. Rumm, K. Kambara, M. I. Bootomo, A. R. Osmack, and N. C. Staub (J. Appl. Physiol. 72: 944-953, 1992) in 39 anesthetized dogs with or without lung edema or pleural effusion. To examine the differential effects of increased-pressure and increased-permeability lung edema on accuracy and sensitivity of ATV and PBF, two models of lung edema were induced by intravenous infusion of a Dextran 70 solution and alloxan monohydrate, respectively. Dogs were hyperventilated for 3 min by using a wide range of minute ventilation (VE) to produce two steady-state conditions of airway temperature. Higher levels of VE increased an estimated amount of ATV. The ATV produced by hyperventilation at VE values of 559, 158, and 72 ml.min-1.kg-1 was consistent with the gravimetric total lung mass, the blood-free wet lung weight, and the extravascular lung water volume, respectively. The coefficient of lung thermal conductivity, a practical index of the rate of heat conduction through tissue from lung vessels, was related to the ratio of the decrease in expired air temperature to VE, and estimated PBF was consistent with the thermodilution cardiac output. Pleural effusion had little effect on measurements of ATV and PBF. However, ATV and PBF showed increased variation in dogs with dextran-induced lung edema.

Alternations in atrial natriuretic peptide release after DC cardioversion of non-valvular chronic atrial fibrillation.

The response of atrial natriuretic peptide (ANP) release to haemodynamic influences after cardioversion of atrial fibrillation has not been fully examined. We measured plasma concentrations of ANP and assessed haemodynamic changes 60-120 min after DC cardioversion in 22 patients with non-valvular chronic atrial fibrillation. Passive leg elevation to enhance volume expansion was performed 60 min after DC cardioversion. Sinus rhythm was restored in 18 of the 22 patients (successful DC cardioversion group). The control group consisted of seven patients with non-valvular chronic atrial fibrillation who did not undergo DC cardioversion (atrial fibrillation control group). In the successful DC cardioversion group, the mean pulmonary artery wedge pressure decreased significantly 15 min after cardioversion (P < 0.05) and then remained unchanged. Plasma concentrations of ANP also decreased significantly 15 min after cardioversion (P < 0.05). Furthermore, there was an additional significant decrease in ANP levels for up to 60 min after cardioversion (P < 0.05 from 15 min). Passive leg elevation for 15 min led to an increase in the mean pulmonary artery wedge pressure (P < 0.01) and right atrial pressure (P < 0.05), but did not result in increased plasma concentrations of ANP (47.1 +/- 27.6 vs 43.9 +/- 34.4 pg.ml-1, mean +/- SD, P = ns). In the atrial fibrillation control group, passive leg elevation increased the mean pulmonary artery wedge pressure (P < 0.01), the mean right atrial pressure (P < 0.05) and plasma concentrations of ANP (139.9 +/- 85.8 vs 168.1 +/- 108.2, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of gastric cancer completely responding to sequential methotrexate and 5-fluorouracil therapy].

A case of an 81-year-old male with Borrmann II type was reported. The lesion was diagnosed histologically as undifferentiated adenocarcinoma. Biochemically modulated chemotherapy preceded by administration of Methotrexate (MTX) and followed by 5-fluorouracil (5-FU) was given to him. The procedure was weekly intermediate-dose therapy consisting of MTX 100 mg (i.v.) followed 3 hours later by 5-FU 600 mg (i.v.) with leucovorin rescue in the following 2 days. After this treatment was repeated 6 times, advanced gastric cancer disappeared on endoscopic and histological findings, so the patient was regarded as showing a complete response. Ths, this biochemically modulated chemotherapy was thought to be in effective method against gastric cancer.

Development of a digital duplication system for portable chest radiographs.

To provide high-quality duplicate chest images for the intensive care units, we have developed a digital duplication system in which film digitization is performed in conjunction with nonlinear density correction, contrast adjustment, and unsharp mask filtering. This system provides consistent image densities over a wide exposure range and enhancement of structures in the mediastinum and upper abdominal areas, improving visibility of catheters and tubes. The image quality is often superior to that of the original radiograph and is more consistent from day to day. Repeat rates for portable chest radiographs have been reduced by more than a factor of two since implementation of digitization in December 1991, and the number of repeat examinations caused by exposure errors have been substantially reduced.

Digital image subtraction of temporally sequential chest images for detection of interval change.

An automated digital image subtraction technique for temporally sequential chest images has been developed in order to aid radiologists in the detection of interval changes. A number of small regions of interest (ROIs) are selected automatically in the lung areas of two temporally sequential chest images. A local matching, based on a cross-correlation method, is performed on each pair of corresponding ROIs in order to determine shift values for the coordinates of two images. A proper warping of x,y coordinates is obtained by fitting two-dimensional polynomials to the distributions of shift values. One of the images is warped and then subtracted from the other. Forty six pairs of chest images (42 with interval changes and 4 without interval change) were processed using this method. The subtraction images were able to enhance various important interval changes, such as differences in the size of tumor masses, changes in heart size, and changes in pulmonary infiltrates or pleural effusions. Approximately 70% of the pairs showed reasonably good registration.

[Urease test].

In order to elucidate bacterial infection, as a rule, isolated and cultured bacteria of a specimen are identified by their morphologies or biochemical characteristics. However, the culture of Helicobacter pylori (H. pylori) is difficult and takes, much time. Therefore, favorable test results are currently obtained by combining the culture method, histopathologic method, urease test and sero-immunologic test. The merits of the urease test are that judgement is available immediately after endoscopy and that the test is inexpensive. The demerits are that the existence of H. pylori is diagnosed only by estimation that endoscopy is indispensable for the test. When compared with the culture method, the urease test has 91.8% sensitivity and 94.7% specificity and when compared with the histopathologic method, it has 94.4% sensitivity 88.4% specificity. In the future, the clinical requirement will increase for quick investigation on the evidence of H. pylori-induced infection. These results show that urease test is useful because it is simple and allows quick judgement.

Effects of acetylsalicylic acid on pulmonary vascular tone and membrane permeability in blood-perfused dog lung.

We studied the effects of acetylsalicylic acid (ASA) on pressor response, microvascular filtration coefficient (Kf), extravascular lung water, and plasma concentrations of cyclooxygenase- and 5-lipoxygenase-derived products in 21 blood-perfused dog lungs with constant flow. The lungs were perfused for 1 h with an intrapulmonary injection of saline as vehicle (n = 5), a low dose of ASA [136 +/- 25 (SD) micrograms/ml perfusate; n = 5], a high dose of ASA (1,006 +/- 278 micrograms/ml perfusate; n = 6), or alloxan (1,000 mg; n = 5). Alloxan significantly increased Kf and extravascular lung water, whereas neither the low nor high dose of ASA increased Kf or extravascular lung water. The ASA-induced increase in vascular resistance did not correlate with the extent of the decrease in perfusate 6-keto-prostaglandin F1 alpha or the ratio of perfusate 6-ketoprostaglandin F1 alpha to thromboxane B2. Moreover, ASA did not enhance the generation of perfusate leukotrienes B4, D4, or E4. We conclude that pulmonary microvascular permeability is unaltered by ASA and that neither the decrease in plasma prostacyclin nor the increase in plasma sulfidopeptide leukotrienes may account for ASA-induced pulmonary vasoconstriction.

Computer-aided diagnosis in chest radiography. Preliminary experience.

RATIONALE AND OBJECTIVES: Computer-aided diagnosis (CAD) schemes for chest radiography are being developed with which to alert radiologists to possible lesions, and thus potentially improve diagnostic accuracy. However, CAD schemes have not been tested on a large number of clinical cases. The authors identify design parameters that would be required for development of an intelligent workstation. METHODS: Computer-aided diagnosis programs were applied for the automated detection of lung nodules, cardiomegaly, and interstitial infiltrates to 310 consecutive chest radiographs, and were analyzed for potential usefulness and limitations. Computer-aided diagnosis output was evaluated by radiologists and physicists for accuracy and technical problems, respectively. RESULTS: Approximately 70% of the results were judged to be potentially acceptable; however, the number of false-positive findings was relatively high. Technical problems included failure to detect subtle abnormalities and the occurrence of false-positive detections caused by normal anatomical structures. CONCLUSION: Computer-aided diagnosis has the potential to be a valuable aid to radiologists in clinical practice, if certain technical problems can be overcome and if optimal operating points can be defined for clinical use.

[Evaluation of the potential benefit of computer-aided diagnosis (CAD) for lung cancer screenings using photofluorography: analysis of an observer study].

To evaluate the potential benefit of computer-aided diagnosis (CAD) in lung cancer screenings using photofluorographic films, we performed an observer test with 12 radiologists. We used 60 photofluorographic films obtained from a lung cancer screening program in Yamaguchi Prefecture (30 contained cancerous nodules and 30 had no nodules). In these cases, our current automated detection scheme achieved a sensitivity of 80%, but yielded an average of 11 false-positives per image. The observer study consisted of three viewing conditions: 1) only the original image (single reading), 2) the original image and computer output obtained from the current CAD scheme (CAD 1), 3) the original image and computer output obtained from a simulated improved CAD scheme with the same 80% true-positive rate, but with an average of one false-positive per image (CAD 2). Compared with double reading using independent interpretations, which is based on a higher score between two single readings, CAD 2 was more sensitive in subtle cases. The specificity of CAD was superior to that of double reading. Although CAD 1 (Az = 0.805) was inferior to double reading (Az = 0.837) in terms of the ROC curve, CAD 2 (Az = 0.872) significantly improved the ROC curve and also significantly reduced observation time (p < 0.05). If the number of false positives can be reduced, computer-aided diagnosis may play an important role in lung cancer screening programs.