Updated evidence of the effectiveness and safety of transanal drainage tube for the prevention of anastomotic leakage after rectal low anterior resection: a systematic review and meta-analysis.

BACKGROUNDS: Anastomotic leakage (AL) represents a major complication after rectal low anterior resection (LAR). Transanal drainage tube (TDT) placement offers a potential strategy for AL prevention; however, its efficacy and safety remain contentious. METHODS: A systematic review and meta-analysis were used to evaluate the influence of TDT subsequent to LAR as part of the revision of the surgical site infection prevention guidelines of the Japanese Society of Surgical Infectious Diseases (PROSPERO registration; CRD42023476655). We searched each database, and included randomized controlled trials (RCTs) and observational studies (OBSs) comparing TDT and non-TDT outcomes. The main outcome was AL. Data were independently extracted by three authors and random-effects models were implemented. RESULTS: A total of three RCTs and 18 OBSs were included. RCTs reported no significant difference in AL rate between the TDT and non-TDT groups [relative risk (RR): 0.69, 95% confidence interval (CI) 0.42-1.15]. OBSs reported that TDT reduced AL risk [odds ratio (OR): 0.45, 95% CI 0.31-0.64]. In the subgroup excluding diverting stoma (DS), TDT significantly lowered the AL rate in RCTs (RR: 0.57, 95% CI 0.33-0.99) and OBSs (OR: 0.41, 95% CI 0.27-0.62). Reoperation rates were significantly lower in the TDT without DS groups in both RCTs (RR: 0.26, 95% CI 0.07-0.94) and OBSs (OR: 0.40, 95% CI 0.24-0.66). TDT groups exhibited a higher anastomotic bleeding rate only in RCTs (RR: 4.28, 95% CI 2.14-8.54), while shorter hospital stays were observed in RCTs [standard mean difference (SMD): -0.44, 95% CI -0.65 to -0.23] and OBSs (SMD: -0.54, 95% CI -0.97 to -0.11) compared with the non-TDT group. CONCLUSIONS: A universal TDT placement cannot be recommended for all rectal LAR patients. Some patients may benefit from TDT, such as patients without DS creation. Further investigation is necessary to identify the specific beneficiaries.

Randomized clinical trial of 24 versus 72 h antimicrobial prophylaxis in patients undergoing open total gastrectomy for gastric cancer.

BACKGROUND: Open total gastrectomy carries a high risk of surgical-site infection (SSI). This study evaluated the non-inferiority of antimicrobial prophylaxis for 24 compared with 72 h after open total gastrectomy. METHODS: An open-label, randomized, non-inferiority study was conducted at 57 institutions in Japan. Eligible patients were those who underwent open total gastrectomy for gastric cancer. Patients were assigned randomly to continued use of ß-lactamase inhibitor for either 24 or 72 h after surgery. The primary endpoint was the incidence of SSI, with non-inferiority based on a margin of 9 percentage points and a 90 per cent c.i. The secondary endpoint was the incidence of remote infection. RESULTS: A total of 464 patients (24 h prophylaxis, 228; 72 h prophylaxis, 236) were analysed. SSI occurred in 20 patients (8·8 per cent) in the 24-h prophylaxis group and 26 (11·0 per cent) in the 72-h group (absolute difference -2·2 (90 per cent c.i. -6·8 to 2·4) per cent; P < 0·001 for non-inferiority). However, the incidence of remote infection was significantly higher in the 24-h prophylaxis group. CONCLUSION: Antimicrobial prophylaxis for 24 h after total gastrectomy is not inferior to 72 h prophylaxis for prevention of SSI. Shortened antimicrobial prophylaxis might increase the incidence of remote infection. Registration number: UMIN000001062 ( http://www.umin.ac.jp).

Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer.

BACKGROUND: Circulating microRNAs (miRNAs) are attracting major interest as potential non-invasive biomarkers for colorectal cancer (CRC). This study aimed to identify a novel serum miRNA biomarker for the early detection and/or evaluating prognosis of CRC patients. PATIENTS AND METHODS: Comprehensive miRNA array analysis was carried out using serum samples from patients with colorectal neoplasia and healthy controls. Next, to verify whether the candidate miRNA possessed a secretory potential, we screened miRNA expression levels in culture medium from 2 CRC cell lines, followed by serum analysis from 12 stage IV CRC, 12 adenoma, and 12 control subjects. Thereafter, we validated expression of candidate miRNAs in 179 primary CRC tissues, as well as serum samples from an independent cohort of 211 CRCs, 56 adenomas, and 57 control subjects. RESULTS: Through microarray analysis, we identified significantly higher levels of miRNA-1290 (miR-1290) in serum from patients with colorectal adenomas and cancers. We verified miR-1290 overexpression in serum of CRC patients in a training cohort. In the validation cohort, serum miR-1290 levels were significantly up-regulated in patients with colorectal adenomas (P < 0.0001) and cancers (P < 0.0001). Serum miR-1290 levels could robustly distinguish adenoma [area under the curve (AUC) = 0.718] and CRC patients (AUC = 0.830) from normal subjects. High miR-1290 expression in serum and tissue was significantly associated with tumor aggressiveness and poor prognosis. Moreover, serum miR-1290 levels were an independent prognostic factor [hazard ratio (HR) = 4.51; 95% confidence interval (CI) = 1.23-23.69; P = 0.0096] and an independent predictor for tumor recurrence (hazard ratio = 3.92; 95% confidence interval = 1.11-25.14; P = 0.032) in CRC. CONCLUSIONS: Serum miR-1290 is a novel biomarker for early detection, recurrence, and prognosis in CRC.

Tropomyosin-related receptor kinase B at the invasive front and tumour cell dedifferentiation in gastric cancer.

BACKGROUND: Tropomyosin-related receptor kinase B (TrkB) promotes proliferation and invasion, relating to poor prognosis of various malignancies. We examined the role of TrkB at the invasive front of gastric cancer (GC) and its association with tumour cell dedifferentiation and tumour budding. METHODS: Immunoreactive TrkB was evaluated at the tumour centre and margin using whole-tissue sections of 320 GC patients. Tumour cell dedifferentiation was defined as higher histologic grade at the tumour margin than the surface or tumour centre. Tumour budding was also scored on cytokeratin-stained sections. RESULTS: Sixty-five patients (20%) showed higher TrkB expression at the invasive front (TrkB expression was higher at the tumour margin than tumour centre). It was significantly associated with several aggressive phenotypes in the full cohort (n=320). It showed a prognostic significance in test subgroup (n=98) and was identified as an independent prognostic factor (HR=2.09; 95% CI: 1.26-3.53) by multivariate analysis in validation subgroup (n=222). Twenty-one patients showed tumour cell dedifferentiation. In predominantly differentiated tumour, higher TrkB at the invasive front was significantly associated with tumour budding rather than tumour cell dedifferentiation. CONCLUSIONS: Assessment of immunoreactive TrkB at the invasive front by whole-tissue sections provides prognostic information for GC patients.

The effectiveness of fascial closure with antimicrobial-coated sutures in preventing incisional surgical site infections in gastrointestinal surgery: a systematic review and meta-analysis.

The aim of this study was to conduct a systematic review and meta-analysis of the efficacy of fascial closure using antimicrobial-sutures specifically for the prevention of surgical site infections (SSIs) in gastrointestinal surgery, as part of the revision of the SSI prevention guidelines of the Japanese Society of Surgical Infectious Diseases (JSSI). We searched CENTRAL, PubMed and ICHUSHI-Web in May 2023, and included randomized controlled trials (RCTs) comparing antimicrobial-coated and non-coated sutures for fascial closure in gastrointestinal surgery (PROSPERO No. CRD42023430377). Three authors independently screened the RCTs. We assessed the risk of bias and the GRADE criteria for the extracted data. The primary outcome was incisional SSI and the secondary outcomes were abdominal wall dehiscence and the length of postoperative hospital stay. This study was supported partially by the JSSI. A total of 10 RCTs and 5396 patients were included. The use of antimicrobial-coated sutures significantly lowered the risk of incisional SSIs compared with non-coated suture (risk ratio: 0.79, 95% confidence intervals: 0.64-0.98). In subgroup analyses, antimicrobial-coated sutures reduced the risk of SSIs for open surgeries, and when monofilament sutures were used. Antimicrobial-coated sutures did not reduce the incidence of abdominal wall dehiscence and the length of hospital stay compared with non-coated sutures. The certainty of the evidence was rated as moderate according to the GRADE criteria, because of risk of bias. In conclusion, the use of antimicrobial-coated sutures for fascial closure in gastrointestinal surgery is associated with a significantly lower risk of SSI than non-coated sutures.

Association between skin suture devices and incidence of incisional surgical site infection after gastrointestinal surgery: systematic review and network meta-analysis.

BACKGROUND: Surgical site infections (SSIs) are common complications after abdominal surgery. AIM: To compare which suture devices could reduce the incidence of incisional surgical site infections (SSIs) after gastrointestinal surgery using a systematic review and network meta-analysis. METHODS: The CENTRAL, PubMed, and ICHUSHI-Web databases were searched from January 1st, 2000, to December 31st, 2022, for randomized clinical trials (RCTs) comparing the incidence of incisional SSI after gastrointestinal surgery among patients treated with different surgical suture devices, including non-absorbable sutures, absorbable sutures, skin staplers, and tissue adhesives (last searched in August 23th, 2023). The risk of bias was assessed using the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. To estimate the pooled odds ratios (ORs) for each comparison, a fixed-effect inverse-variance model based on the Mantel-Haenszel approach was employed. FINDINGS: A total of 18 RCTs with 5496 patients were included in this study. The overall SSIs in absorbable sutures were significantly lower than those in skin staplers (OR: 0.77; 95% confidence intervals (CI): 0.63-0.95) and non-absorbable sutures (OR: 0.62; 95% CI: 0.39-0.99), whereas SSIs in absorbable sutures were not significantly different from the SSIs in tissue adhesive. The highest P-score was 0.91 for absorbable sutures. A funnel plot for estimating the heterogeneity of the studies revealed that a publication bias would be minimal (Egger test, P = 0.271). CONCLUSION: This study showed that absorbable sutures reduced incisional SSIs in gastrointestinal surgical operations compared to any other suture devices.

Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer.

BACKGROUND: Brain-derived neutrophic factor (BDNF) is a member of the neutrophin family that is known to activate the high-affinity tropomyosin-related receptor kinase B (TrkB). This study aimed to clarify the clinical and biological significance of the BDNF/TrkB pathway in gastric cancer. METHODS: We analysed BDNF and TrkB expression in gastric cancer samples by real-time reverse transcription PCR and immunohistochemistry. To investigate the biological role of BDNF/TrkB axis, recombinant human BDNF (rhBDNF) and the Trk antagonist K252a were used for in vitro and in vivo analysis. RESULTS: The BDNF expression at the invasive front of primary tumours was significantly elevated compared with that in the tumour core and adjacent normal mucosa. Increased BDNF expression at the invasive front was significantly correlated with factors reflecting disease progression, and poor prognosis. Increased co-expression of the BDNF/TrkB axis was significantly correlated with poor prognosis. Gastric cancer cells expressed BDNF, and administration of rhBDNF promoted proliferation, migration, invasion, and inhibition of anoikis. These effects were generally inhibited by K252a. In an in vivo assay, BDNF(+)/TrkB(+) gastric cancer cells injected into nude mice established peritoneal dissemination, whereas K252a inhibited tumour growth. CONCLUSION: The BDNF/TrkB pathway might be deeply involved in gastric cancer disease progression.

Macrophage migration inhibitory factor and DJ-1 in gastric cancer: differences between high-incidence and low-incidence areas.

BACKGROUND: There is a need for sensitive and specific blood-borne markers for the detection of gastric cancer. Raised serum macrophage inhibitory factor (MIF) levels have been proposed as a marker for gastric cancer diagnosis but, to date, studies have only encompassed patients from high-incidence areas. METHODS: We have compared the serum concentration of MIF in a large cohort of UK and Japanese gastric cancer patients, together with appropriate control subjects (age and gender matched). Carcinoembryonic antigen and H. pylori IgG were also measured, as was DJ-1, a novel candidate protein biomarker identified by analysis of gastric cancer cell line secretomes. RESULTS: Marked elevations of the serum concentration of MIF and DJ-1 were seen in Japanese patients with gastric cancer compared with Japanese controls, a trend not seen in the UK cohort. These results could not be accounted for by differences in age, disease stage or H. pylori status. CONCLUSION: In regions of high, but not low incidence of gastric cancer, both MIF and DJ-1 have elevated serum concentrations in gastric cancer patients, compared with controls. This suggests that differing mechanisms of disease pathogenesis may be at play in high- and low-incidence regions.

Identification of macrophage migration inhibitory factor and human neutrophil peptides 1-3 as potential biomarkers for gastric cancer.

BACKGROUND: Proteomic methods have the potential to meet the urgent need for better cancer biomarkers. We have used a range of proteomic analyses of serum and tissue from gastric cancer patients and relevant controls to discover biomarkers for gastric cancer. METHODS: Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI) and antibody arrays were used to compare protein expression in 21 pairs of gastric cancer tissue and adjacent normal mucosa and serum from 51 gastric cancer patients and 29 patients with benign gastric diseases. Expression differences were confirmed by enzyme-linked immunosorbent assay. RESULTS: Tissue analysis shows human neutrophil peptides 1-3 (HNPs 1-3) elevated 10-fold (P=0.001) in gastric cancer relative to adjacent normal mucosa. Macrophage migration inhibitory factor (MIF) was increased five-fold (P=1.84 x 10(-7)) in the serum of gastric cancer patients relative to individuals with benign gastric disease. The large increase in MIF concentration in serum gives an area under the receiver operating characteristic curve of 0.85. CONCLUSIONS: Proteomic analyses of serum and tissue indicate that HNPs 1-3 and MIF have potential as biomarkers for gastric cancer. In particular MIF may be useful, either alone or in combination with other markers, for diagnosing and monitoring gastric cancer.

Mitotic checkpoint genes, hsMAD2 and BubR1, in oesophageal squamous cancer cells and their association with 5-fluorouracil and cisplatin-based radiochemotherapy.

AIMS: HsMAD2 and BubR1 are crucial components of a functional mitotic checkpoint. Recently, impaired mitotic checkpoints or decreased expression of mitotic checkpoint genes have been associated with sensitivity to certain anticancer drugs. The current study aimed to evaluate the association of hsMAD2 and BubR1 with sensitivity to various anticancer drugs in oesophageal squamous cell carcinoma (ESCC) cell lines. We also investigated responses to 5-fluorouracil and cisplatin-based radiochemotherapy in ESCC patients. MATERIALS AND METHODS: HsMAD2 and BubR1 mRNA levels in six ESCC cell lines and 21 ESCC patients were determined by real-time reverse transcription polymerase chain reaction. Responses to 5-fluorouracil, cisplatin, paclitaxel and docetaxel in human oesophageal cancer cell lines, TE1 and TE2, were evaluated by WST-8 colorimetric assay. HsMAD2 and BubR1 levels were compared with clinicopathological characteristics and responses to radiochemotherapy. RESULTS: TE1, with lower hsMAD2 and BubR1, showed greater sensitivity to paclitaxel and docetaxel compared with TE2, with higher hsMAD2 and BubR1. HsMAD2 and BubR1 were significantly higher in cancer tissue than in adjacent normal tissue (P < 0.01). Tumoral hsMAD2 and BubR1 were significantly decreased after radiochemotherapy (P < 0.01). There was a significantly strong positive association between hsMAD2 and BubR1 in cancer tissue (P < 0.01). Neither clinicopathological characteristics nor the response to radiochemotherapy was associated with hsMAD2 or BubR1. CONCLUSION: The mitotic checkpoint genes, hsMAD2 and BubR1, were co-ordinately overexpressed in ESCC. Low hsMAD2 and BubR1 was associated with sensitivity to paclitaxel and docetaxel. Decreased hsMAD2 and BubR1 after radiochemotherapy may indicate the potential efficacy of taxanes as second-line chemotherapy for recurrent and metastatic oesophageal cancer.

Perioperative allogeneic blood transfusion, the related cytokine response and long-term survival after potentially curative resection of colorectal cancer.

AIMS: It is still debated whether perioperative blood transfusion alters the incidence of disease recurrence or otherwise affects the prognosis after curative resection of malignant tumours. We conducted a prospective observational study of patients with colorectal cancer to provide data on the effect of blood transfusion and the related perioperative cytokine response on long-term prognosis. MATERIALS AND METHODS: Perioperative blood samples were obtained from 117 patients with colorectal cancer undergoing potentially curative resection. Factors associated with perioperative blood transfusion were assessed, and their relationship with early postoperative systemic responses of tumour growth factors and long-term prognosis were evaluated. RESULTS: Independent factors associated with perioperative blood transfusion were preoperative anaemia, operative blood loss and the development of postoperative infectious complication. The patients receiving transfusions were subdivided according to the independent factors. Group A comprised 19 patients who received blood transfusions because of preoperative anaemia and Group B comprised 16 patients who received blood transfusions because of excessive operative blood loss. Group B patients showed exaggerated postoperative systemic induction of interleukin (IL)-6 and IL-6-triggered tumour growth factors, such as hepatocyte growth factor and vascular cell adhesion molecule-1. Intraoperative blood transfusion under intense surgical stress was associated with poor prognosis, whereas preoperative blood transfusion for correcting anaemia or intraoperative blood transfusion under less invasive surgery was not associated with survival. Multivariate analysis using the Cox proportional hazards method showed that a significant independent risk was demonstrated for blood transfusion, T stage, lymph-node metastasis and perioperative peak levels of IL-6. CONCLUSION: Blood transfusion and intense surgical stress might synergistically affect the long-term prognosis after curative resection of colorectal cancer. Postoperative exaggerated systemic inductions of IL-6 may indicate the critical situation that could lead to disease recurrence.

Megavoltage imaging with a large-area, flat-panel, amorphous silicon imager.

PURPOSE: The creation of the first large-area, amorphous silicon megavoltage imager is reported. The imager is an engineering prototype built to serve as a stepping stone toward the creation of a future clinical prototype. The engineering prototype is described and various images demonstrating its properties are shown including the first reported patient image acquired with such an amorphous silicon imaging device. Specific limitations in the engineering prototype are reviewed and potential advantages of future, more optimized imagers of this type are presented. METHODS AND MATERIALS: The imager is based on a two-dimensional, pixelated array containing amorphous silicon field-effect transistors and photodiode sensors which are deposited on a thin glass substrate. The array has a 512 x 560-pixel format and a pixel pitch of 450 microns giving an imaging area of approximately 23 x 25 cm2. The array is used in conjunction with an overlying metal plate/phosphor screen converter as well as an electronic acquisition system. Images were acquired fluoroscopically using a megavoltage treatment machine. RESULTS: Array and digitized film images of a variety of anthropomorphic phantoms and of a human subject are presented and compared. The information content of the array images generally appears to be at least as great as that of the digitized film images. CONCLUSION: Despite a variety of severe limitations in the engineering prototype, including many array defects, a relatively slow and noisy acquisition system, and the lack of a means to generate images in a radiographic manner, the prototype nevertheless generated clinically useful information. The general properties of these amorphous silicon arrays, along with the quality of the images provided by the engineering prototype, strongly suggest that such arrays could eventually form the basis of a new imaging technology for radiotherapy localization and verification. The development of a clinically useful prototype offering high-quality images, ultimately with an approximately 52 x 52-cm2 detection surface, is anticipated.

Initial performance evaluation of an indirect-detection, active matrix flat-panel imager (AMFPI) prototype for megavoltage imaging.

PURPOSE: The development of the first prototype active matrix flat-panel imager (AMFPI) capable of radiographic and fluoroscopic megavoltage operation is reported. The signal and noise performance of individual pixels is empirically quantified. Results of an observer-dependent study of imaging performance, using a contrast-detail phantom, are detailed and radiographic patient images are shown. Finally, a theoretical investigation of the zero-frequency detective quantum efficiency (DQE) performance of such imagers, using a cascaded systems formalism, is presented. METHODS AND MATERIALS: The imager is based on a 508-microm pitch, 26 x 26 cm2 array which detects radiation indirectly via an overlying copper plate + phosphor screen converter. RESULTS: Due to its excellent optical coupling, the imager exhibits sensitivity superior to that of video-based systems. With an approximately 133 mg/cm2 Gd2O2S:Tb screen the system is x-ray quantum-noise-limited down to approximately 0.3 cGy, conservatively, and extensions of this behavior to even lower doses by means of reduced additive electronic noise is predicted. The observer-dependent study indicates performance superior to that of conventional radiotherapy film while the patient images demonstrate good image quality at 1 to 4 MU. The theoretical studies suggest that, with a 133 mg/cm2 Gd2O2S:Tb screen, the system would provide DQE performance equivalent to that of video-based systems and that almost a factor of two improvement in DQE is achievable through the incorporation of a 400 mg/cm2 screen. CONCLUSION: The reported prototype imager is the first megavoltage AMFPI having performance characteristics consistent with practical clinical operation. The superior contrast-detail sensitivity of the imager allows the capture of high-quality 6- and 15-MV images at minimal dose. Moreover, significant performance improvements, including extension of the operational range up to full portal doses, appear feasible. Such capabilities could be of considerable practical benefit in patient localization and verification.

Withdrawal from nicotine facilitates diazepam binding inhibitor mRNA expression in mouse cerebral cortex.

Changes in diazepam binding inhibitor (DBI) mRNA expression after withdrawal from nicotine were examined. Withdrawal from nicotine Increased DBI mRNA expression in cerebral cortices derived from nicotine-dependent mice and in the neurons continuously exposed to nicotine (0.1 microM). These results indicate that withdrawal from nicotine after its long-term exposure induces steep increase of DBI mRNA expression as reported previously in ethanol- and morphine-dependent animals.

Mechanism for increase in expression of cerebral diazepam binding inhibitor mRNA by nicotine: involvement of L-type voltage-dependent calcium channels.

We investigated the mechanisms underlying the increase in diazepam binding inhibitor (DBI) and its mRNA expression induced by nicotine (0.1 microM) exposure for 24 h using mouse cerebral cortical neurons in primary culture. Nicotine-induced (0.1 microM) increases in DBI mRNA expression were abolished by hexamethonium, a nicotinic acetylcholine (nACh) receptor antagonist. Agents that stabilize the neuronal membrane, including tetrodotoxin (TTX), procainamide (a Na(+) channel inhibitor), and local anesthetics (dibucaine and lidocaine), dose-dependently inhibited the increased expression of DBI mRNA by nicotine. The nicotine-induced increase in DBI mRNA expression was inhibited by L-type voltage-dependent Ca(2+) channel (VDCC) inhibitors such as verapamil, calmodulin antagonist (W-7), and Ca(2+)/calmodulin-dependent protein kinase II (CAM II kinase) inhibitor (KN-62), whereas P/Q- and N-type VDCC inhibitors showed no effects. In addition, nicotine exposure for 24 h induced [3H]nicotine binding to the particulate fractions of the neurons with an increased B(max) value and no changes in K(d). Under these conditions, the 30 mM KCl- and nicotine-induced 45Ca(2+) influx into the nicotine-treated neurons was significantly higher than those into non-treated neurons. These results suggest that the nicotine-stimulated increase in DBI mRNA expression is mediated by CAM II kinase activation resulting from the increase in intracellular Ca(2+) through L-type VDCCs subsequent to the neuronal membrane depolarization associated with nACh receptor activation.

Suppression of Ca2+ influx through L-type voltage-dependent calcium channels by hydroxyl radical in mouse cerebral cortical neurons.

In the present study, we investigated the effect of hydroxyl radical (.OH) produced by the Fenton reaction with FeSO(4) to H(2)O(2) on Ca2+ influx by measuring [(45)Ca2+] influx into mouse cerebral cortical neurons in primary culture.OH formed from 3 microM FeSO(4) and 0.01 microM H(2)O(2) significantly reduced 30 mM KCl-induced [(45)Ca2+] influx and this reduction was abolished by .OH scavengers such as N,N'-dimethylthiourea and mannitol. Nifedipine (1 microM), an inhibitor for L-type voltage-dependent Ca2+ channels (VDCCs) showed no additive effect on the reduction of the 30 mM KCl-induced [(45)Ca2+] influx, while the inhibitors for P/Q- and N-type VDCCs showed further suppression of the KCl-induced [(45)Ca2+] influx even in the presence of .OH. Bay k 8644, an activator of L-type VDCCs, dose-dependently stimulated [(45)Ca2+] influx, and this stimulation disappeared in the presence of nifedipine. Similarly, .OH also suppressed significantly [(45)Ca2+] influx induced by Bay k 8644. These inhibitory actions of .OH on the KCl- and Bay k 8644-induced [(45)Ca2+] influx were completely abolished by .OH scavengers. These results indicate that .OH has the activity to suppress Ca2+ influx through L-type VDCCs.

NMDA receptor activation enhances diazepam binding inhibitor and its mRNA expressions in mouse cerebral cortical neurons.

Effects of N-methyl-D-aspartate (NMDA) on diazepam binding inhibitor (DBI) and its mRNA expression in mouse cerebral cortical neurons were examined. A significant increase in DBI mRNA expression was observed 1 day after the exposure to 0.1 microM NMDA and the maximal expression occurred 2 days after the exposure, whereas transient exposure to 0.1 microM NMDA for 15 min, 1 and 3 h produced no changes in the expression. Similarly, no changes in the expression were found by the concomitant exposure to NMDA and MK-801, a NMDA receptor antagonist, for 72 h subsequent to the incubation with NMDA alone for 3 h. Such NMDA-induced increases in DBI mRNA expression were dose-dependently inhibited by MK-801. Moreover, neuronal DBI content significantly increased by treatment with NMDA, which was completely abolished by MK-801. These results indicate that continuous activation of NMDA receptors is an essential factor for increasing DBI expression in the neurons.

Signal, noise power spectrum, and detective quantum efficiency of indirect-detection flat-panel imagers for diagnostic radiology.

The performance of an indirect-detection, active matrix flat-panel imager (FPI) at diagnostic energies is reported in terms of measured and theoretical signal size, noise power spectrum (NPS), and detective quantum efficiency (DQE). Based upon a 1536 x 1920 pixel, 127 microns pitch array of a-Si:H thin-film transistors and photodiodes, the FPI was developed as a prototype for examination of the potential of flat-panel technology in diagnostic x-ray imaging. The signal size per unit exposure (x-ray sensitivity) was measured for the FPI incorporating five commercially available Gd2O2S:Tb converting screens at energies 70-120 kVp. One-dimensional and two-dimensional NPS and DQE were measured for the FPI incorporating three such converters and as a function of the incident exposure. The measurements support the hypothesis that FPIs have significant potential for application in diagnostic radiology. A cascaded systems model that has shown good agreement with measured individual pixel signal and noise properties is employed to describe the performance of various FPI designs and configurations under a variety of diagnostic imaging conditions. Theoretical x-ray sensitivity, NPS, and DQE are compared to empirical results, and good agreement is observed in each case. The model is used to describe the potential performance of FPIs incorporating a recently developed, enhanced array that is commercially available and has been proposed for testing and application in diagnostic radiography and fluoroscopy. Under conditions corresponding to chest radiography, the analysis suggests that such systems can potentially meet or even exceed the DQE performance of existing technology, such as screen-film and storage phosphor systems; however, under conditions corresponding to general fluoroscopy, the typical exposure per frame is such that the DQE is limited by the total system gain and additive electronic noise. The cascaded systems analysis provides a valuable means of identifying the limiting stages of the imaging system, a tool for system optimization, and a guide for developing strategies of FPI design for various imaging applications.

Determination of the detective quantum efficiency of a prototype, megavoltage indirect detection, active matrix flat-panel imager.

After years of aggressive development, active matrix flat-panel imagers (AMFPIs) have recently become commercially available for radiotherapy imaging. In this paper we report on a comprehensive evaluation of the signal and noise performance of a large-area prototype AMFPI specifically developed for this application. The imager is based on an array of 512 x 512 pixels incorporating amorphous silicon photodiodes and thin-film transistors offering a 26 x 26 cm2 active area at a pixel pitch of 508 microm. This indirect detection array was coupled to various x-ray converters consisting of a commercial phosphor screen (Lanex Fast B, Lanex Regular, or Lanex Fine) and a 1 mm thick copper plate. Performance of the imager in terms of measured sensitivity, modulation transfer function (MTF), noise power spectra (NPS), and detective quantum efficiency (DQE) is reported at beam energies of 6 and 15 MV and at doses of 1 and 2 monitor units (MU). In addition, calculations of system performance (NPS, DQE) based on cascaded-system formalism were reported and compared to empirical results. In these calculations, the Swank factor and spatial energy distributions of secondary electrons within the converter were modeled by means of EGS4 Monte Carlo simulations. Measured MTFs of the system show a weak dependence on screen type (i.e., thickness), which is partially due to the spreading of secondary radiation. Measured DQE was found to be independent of dose for the Fast B screen, implying that the imager is input-quantum-limited at 1 MU, even at an extended source-to-detector distance of 200 cm. The maximum DQE obtained is around 1%--a limit imposed by the low detection efficiency of the converter. For thinner phosphor screens, the DQE is lower due to their lower detection efficiencies. Finally, for the Fast B screen, good agreement between calculated and measured DQE was observed.