Using spatial metrics and surveys for the assessment of trans-boundary deforestation in protected areas of the Maya Mountain Massif: Belize-Guatemala border.

Understanding the trans-boundary deforestation history and patterns in protected areas along the Belize-Guatemala border is of regional and global importance. To assess deforestation history and patterns in our study area along a section of the Belize-Guatemala border, we incorporated multi-temporal deforestation rate analysis and spatial metrics with survey results. This multi-faceted approach provides spatial analysis with relevant insights from local stakeholders to better understand historic deforestation dynamics, spatial characteristics and human perspectives regarding the underlying causes thereof. During the study period 1991-2014, forest cover declined in Belize's protected areas: Vaca Forest Reserve 97.88%-87.62%, Chiquibul National Park 99.36%-92.12%, Caracol Archeological Reserve 99.47%-78.10% and Colombia River Forest Reserve 89.22%-78.38% respectively. A comparison of deforestation rates and spatial metrics indices indicated that between time periods 1991-1995 and 2012-2014 deforestation and fragmentation increased in protected areas. The major underlying causes, drivers, impacts, and barriers to bi-national collaboration and solutions of deforestation along the Belize-Guatemala border were identified by community leaders and stakeholders. The Mann-Whitney U test identified significant differences between leaders and stakeholders regarding the ranking of challenges faced by management organizations in the Maya Mountain Massif, except for the lack of assessment and quantification of deforestation (LD, SH: 18.67, 23.25, U = 148, p > 0.05). The survey results indicated that failure to integrate buffer communities, coordinate among managing organizations and establish strong bi-national collaboration has resulted in continued ecological and environmental degradation. The information provided by this research should aid managing organizations in their continued aim to implement effective deforestation mitigation strategies.

Right portal vein embolization with absolute ethanol in major hepatic resection for hepatobiliary malignancy.

BACKGROUND: This study aimed to evaluate the safety and efficacy of preoperative right portal vein embolization (PVE) with absolute ethanol in patients with hepatobiliary malignancies. METHODS: PVE was performed via a percutaneous transhepatic ipsilateral approach, and the right portal branch was embolized with absolute ethanol. Technical success and complications following PVE, and changes in liver enzyme levels were evaluated. Changes in future liver remnant (FLR) and FLR/total functional liver volume ratio were calculated. Complications following hepatic resection were assessed. RESULTS: A total of 83 patients with hepatobiliary malignancies (53 men, 30 women; mean age 68 years) underwent right PVE. Tumour types were hilar cholangiocarcinoma (37), liver metastases (14), gallbladder cancer (13), intrahepatic cholangiocellular carcinoma (10) and hepatocellular carcinoma (HCC) (9). PVE was performed successfully in all patients. Four patients (5 per cent) developed complications following PVE (liver abscess 2, left portal vein thrombosis 1, pseudoaneurysm 1), but this did not preclude hepatic resection. Liver enzyme levels rose transiently after PVE. The mean FLR and FLR/total functional liver volume increased after PVE (from 366 to 513 cm(3) and from 31 to 43 per cent respectively; both P < 0·001). Changes in the FLR and FLR/total functional liver volume ratio were comparable between patients with HCC and those with other malignancies (42 and 44 per cent, and 12 and 12 per cent, respectively). Sixty-nine of 83 patients underwent hepatic resection at a median of 25 days after PVE, with no postoperative mortality. CONCLUSION: Preoperative right PVE with absolute ethanol is safe and effective for induction of selective hepatic hypertrophy in patients with hepatobiliary malignancy.

Comparative study of non-invasive force and stress inference methods in tissue.

In the course of animal development, the shape of tissue emerges in part from mechanical and biochemical interactions between cells. Measuring stress in tissue is essential for studying morphogenesis and its physical constraints. For that purpose, a possible new approach is force inference (up to a single prefactor) from cell shapes and connectivity. It is non-invasive and can provide space-time maps of stress in a whole tissue, unlike existing methods. To validate this approach, three force-inference methods, which differ in their approach of treating indefiniteness in an inverse problem between cell shapes and forces, were compared. Tests using two artificial and two experimental data sets consistently indicate that our Bayesian force inference, by which cell-junction tensions and cell pressures are simultaneously estimated, performs best in terms of accuracy and robustness. Moreover, by measuring the stress anisotropy and relaxation, we cross-validated the force inference and the global annular ablation of tissue, each of which relies on different prefactors. A practical choice of force-inference methods in different systems of interest is discussed.

High expression of Lin28 is associated with tumour aggressiveness and poor prognosis of patients in oesophagus cancer.

BACKGROUND: Lin28 is a negative regulator of the tumour suppressor microRNA, let-7, suggesting its role in tumourigenesis. However, the clinical significance of Lin28 expression in oesophageal cancer has not been elucidated. METHODS: Lin28 and Lin28B expression was examined by immunohistochemistry in 161 tissues from patients with oesophageal cancer who had undergone curative surgery. The relationship between the expressions of Lin28 and Lin28B and various clinicopathological factors was examined. In vitro assays were conducted to determine the role of Lin28 in aggressiveness of oesophageal cancers using oesophageal cancer cell line. RESULTS: Lin28 and Lin28B were overexpressed in oesophageal cancer cells compared with non-cancerous epithelial cells, especially in the invasive front. High expression of Lin28 and Lin28B correlated significantly with lymph node metastasis and poor prognosis. High expression of Lin28B expression correlated significantly with low expression of let-7. Multivariate analysis also identified Lin28B expression as an independent prognostic factor. In vitro assays showed that the proliferative and invasive activities were significantly reduced in Lin28B-knockdown cells, compared with control cells. CONCLUSION: High expression of Lin28 is associated with poor prognosis and high tumour aggressiveness in oesophageal cancer and these effects are mediated through increased proliferation and invasiveness of oesophageal cancer cells.

Ten cases of gastro-tracheobronchial fistula: a serious complication after esophagectomy and reconstruction using posterior mediastinal gastric tube.

Gastro-tracheobronchial fistula (GTF) is a rare but life-threatening complication specifically observed after esophagectomy and reconstruction using posterior mediastinal gastric tube. Ten cases of GTF were encountered in three hospitals in 2000-2009. Their clinicopathological, surgical, and postoperative care are summarized, together with a review of previously reported cases. GTF was classified as anastomotic leakage (n= 5), gastric necrosis (n= 4), and gastric ulcer type (n= 1). The anastomotic leakage type appeared about 2 weeks (postoperative day [POD]: 8-35) after esophagectomy, was located in the cervical or higher thoracic trachea. Breathing and pneumonia were controlled by tracheal tube placed in the distal of fistula. The gastric necrosis type was noted in patients who developed necrosis of the upper part of the gastric tube and abscess formation behind the tracheal wall, at POD 20-36 around the carina, the site of pronounced ischemia. Due to the large fistula around the carina, emergency surgery with muscle patch repair was frequently required for the control of aspiration pneumonia. Patients of the gastric ulcer type had peptic ulcer in the lesser curvature of the gastric tube, which perforated into the right bronchus long after surgery (POD 630). With respect to tracheobronchial factors, preoperative chemoradiation (three cases) and pre-tracheal node dissection (three cases) tended to increase the risk of GTF. Closure of GTF by surgery (muscle patch repair) was successful in four cases and by nonsurgical treatment in three cases. In one case, stable oral intake was achieved by bypass operation without closure of GTF. Hospital death occurred in three cases. Understanding the pathogenesis and treatment options of GTF is important for surgeons who deal with esophageal cancer.

Established, emerging and future applications of FDG-PET/CT in the uterine cancer.

Integrated positron emission tomography/computed tomography (PET/CT) with 2-[¹8F]fluoro-2-deoxy-D-glucose (FDG) is a useful technique to acquire both glucose metabolic and anatomic imaging data using a single device in a single diagnostic session and has opened a new field in clinical oncologic imaging. FDG-PET/CT has been used successfully for the staging, optimization of treatment, re-staging, therapy monitoring, and prognostic prediction of uterine cervical cancer and endometrial cancer as well as various malignant tumours. The present review discusses the current role of FDG-PET/CT in the management of uterine cancer, discussing its usefulness and limitations in the imaging of these patients.

FDG PET/CT features of ovarian metastasis.

AIM: To assess the characteristics of [(18)F]-fluoro-2-deoxy-d-glucose (FDG) uptake in cases of ovarian metastasis using positron-emission tomography/computed tomography (PET/CT). MATERIALS AND METHODS: Twelve patients with 16 ovarian metastases arising from colon cancer (n=6), breast cancer (n=4), gastric cancer (n=3), and pancreatic cancer (n=3) who underwent FDG-PET/CT examination were included in this study. The effect of lesion size and morphological pattern (predominantly solid or cystic) on FDG uptake was evaluated using the quantitative standardized uptake value (SUV). RESULTS: The mean maximum SUV for the 16 lesions was 4.6±2.4 (range 1.8∼9.9). The Pearson correlation coefficient test showed no significant correlation between maximum SUV and lesion size (r=0.21, p=0.42). The maximum SUV of solid (n=5) and cystic (n=11) lesions was 5.5±2.7 and 4.3±2.2, respectively, and the difference was not significant (p=0.43). Breast cancer showed the highest maximum SUV (6.4±3.6), followed by colon cancer (5.3±1.4), gastric cancer (3.3±0.5), and pancreatic cancer (2.2±0.6). CONCLUSION: Ovarian metastases show a variable maximum SUV with mild to intense FDG uptake.

Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells.

BACKGROUND: The hypothesis that malignant tumours are generated by rare populations of cancer stem cells that are more tumourigenic than other cancer cells has gained increasing credence. The objective of this study was to identify and characterise a subpopulation of human sarcoma-initiating cells. METHODS: We examined established rhabdomyosarcoma cell lines by flow cytometry. Tumourigenesis was examined by xenograft models. Real-time PCR and immunohistochemistry were performed to examine the gene expression using cell lines and biopsy specimens. RESULTS: Rhabdomyosarcoma cell lines included small populations of fibroblast growth factor receptor 3 (FGFR3)-positive cells. FGFR3-positive KYM-1 and RD cells were more strongly tumourigenic than FGFR3-negative cells. In addition, xenoengraftment of 33% of single FGFR3-positive KYM-1 cells yielded tumour formation. Stem cell properties of FGFR3-positive cells were further established by real-time PCR, which demonstrated upregulation of undifferentiated cell markers and downregulation of differentiation markers. We showed that in the absence of serum, addition of basic fibroblast growth factor maintained and enriched FGFR3-positive cells. On the other hand, ciliary neurotrophic factor reduced the proportion of FGFR3-positive cells. Real-time PCR and immunohistochemical examination revealed that embryonal rhabdomyosarcoma patient biopsy specimens were found to over-express FGFR3. CONCLUSIONS: Our findings suggest that rhabdomyosarcoma cell lines include a minor subpopulation of FGFR3-positive sarcoma-initiating cells, which can be maintained indefinitely in culture and which is crucial for their malignancy.

Peptide mimics of the CTLA4-binding domain stimulate T-cell proliferation.

Phage library clones selected by a conformational epitope-recognizing and inhibitory monoclonal antibody may display moieties that mimic a receptor/ligand-like three-dimensional structure. This pseudoreceptor/ligand should be able to bind to natural ligand/receptor molecules. We tested this idea using anti-T cell costimulatory molecule antibodies and successfully isolated phage clones with costimulatory effects on T-cell proliferation. This strategy facilitates the designing of regulatory peptide molecules in the absence of precise information about the structure-function relationships in receptor/ligand interactions.

Advantages of 70-kV CT Angiography for the Visualization of the Adamkiewicz Artery: Comparison with 120-kV Imaging.

BACKGROUND AND PURPOSE: Preprocedural identification of the Adamkiewicz artery is crucial in patients with aortic diseases. This study aimed to compare 70-kV CTA with conventional 120-kV CTA for the identification of the Adamkiewicz artery, examining differences in radiation dose and image quality. MATERIALS AND METHODS: We retrospectively analyzed 2 equal groups of 60 patients who had undergone 70-kV or 120-kV CTA to detect the Adamkiewicz artery before aortic repair. Size-specific dose estimate, the CT number of the aorta, and the contrast-to-noise ratio of the anterior spinal artery to the spinal cord were recorded. Furthermore, detectability of the Adamkiewicz artery was evaluated by using a 4-point continuity score (3, definite to 0, undetectable). RESULTS: There was significantly lower radiation exposure with 70-kV CTA than 120-kV CTA (median size-specific dose estimate, 23.1 versus 61.3 mGy, respectively; P < .001). CT number and contrast-to-noise ratio were both significantly higher in the 70-kV CTA group than the 120-kV group (999.1 HU compared with 508.7 HU, and 5.6 compared with 3.4, respectively; P < .001 for both). Detectability of the Adamkiewicz artery was not impaired in the 70-kV CTA group (90.0% versus 83.3% in the 120-kV group, P = .28). Moreover, the Adamkiewicz artery was detected with greater confidence with 70-kV CTA, reflected by a significantly superior continuity score (median, 3) compared with 120-kV CTA (median, 2; P = .001). CONCLUSIONS: Seventy-kilovolt CTA has substantial advantages for the identification of the Adamkiewicz artery before aortic repair, with a significantly lower radiation exposure and superior image quality than 120-kV CTA.

FDG-PET predicts treatment efficacy and surgical outcome of pre-operative chemoradiation therapy for resectable and borderline resectable pancreatic cancer.

BACKGROUND: The efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectable and borderline resectable pancreatic cancer is important for predicting outcomes after radical surgery, but few clinical indicators predict outcome before resection. This study examined the utility of FDG-PET in predicting the efficacy of NACRT and outcome after radical surgery. METHODS: Eighty-three pancreatic cancer patients who underwent FDG-PET before and after NACRT and had positive standard uptake values (SUVs) before NACRT were enrolled in this study. Peri-operative clinical factors, including FDG-PET findings, were examined to predict the efficacy of NACRT and outcome after surgery. RESULTS: Evans grade I, IIA, IIB, III, and IV was determined in 11, 31, 27, 11, and 3 patients, respectively. The maximum SUVs after NACRT (post SUV-max) and tumor size were significantly decreased compared to pretreatment values (p < 0.001 and p = 0.007, respectively). The post SUV-max and regression index were significantly related to grade III/IV (p = 0.04 and p < 0.001, respectively), but only the regression index predicted NACRT efficacy (p = 0.002). The AUC of the regression index for the detection of grade III/IV was 0.822, and 13 of 14 grade III/IV patients were picked up using 50% as the threshold (p < 0.001). Patients with a regression index >50% had a significantly better prognosis after radical resection than patients with <50% (p = 0.032). Regression index as well as pathological lymph node status and resectability status were independent prognostic factors in multivariate analysis (exp 2.086, p = 0.043). CONCLUSION: The regression index is potentially a good indicator of the efficacy of NACRT and outcome after radical resection for pancreatic cancer.

Expression and function of human steroid receptor RNA activator in prostate cancer cells: role of endogenous hSRA protein in androgen receptor-mediated transcription.

Steroid receptor RNA activator (SRA) was first isolated as a steroid receptor co-activator that functioned as an RNA transcript. Later, we demonstrated that SRA needs to be translated in order to co-activate androgen receptor (AR). Here, we showed that three isoforms of human SRA enhanced AR activities. Small interfering RNA against SRA suppressed AR activities in PC-3 cells transfected with pSG5AR and in LNCaP cells that have an endogenous mutated-AR. Western blot showed that SRA protein was expressed at a higher level in PC-3 than in LNCaP cells, suggesting that SRA may be related to hormone-independent growth of prostate cancer.

Treatment with edaravone improves the survival rate in renal warm ischemia-reperfusion injury using rat model.

Renal ischemia-reperfusion (I/R) injury during renal transplantation is a significant cause of renal dysfunction. The pathological role of free radicals in this process is a major concern. We investigated the effect of a free radical scavenger, edaravone (MCI-186), in renal I/R injury. Male Lewis rats (270 to 320 g) were used for the model. The right kidney was harvested and left renal artery and vein were clamped as laparotomy. The kidney was reperfused after 90 minutes of ischemia. Edaravone (10 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent the neutrophil activation. In the nontreatment I/R group, no rat survived beyond 4 days. However, in the edaravone I/R treatment group, one among five rats survived more than 7 days. These results suggested that treatment with edaravone ameliorated renal I/R injury, and that the agent has the potential to ameliorate preservation injury in renal transplantation.

Tumor growth inhibitory activity of a lymphocyte blastogenesis inhibitory factor.

A lymphocyte blastogenesis inhibitory factor (LBIF) has been characterized as an immunoregulatory molecule, especially on the T-lymphocyte proliferation. Using fast protein liquid chromatography-purified LBIF, we examined the effect of LBIF on the proliferation of various 18 tumor cell lines in vitro in comparison with those of interferon-alpha, interferon-gamma, tumor necrosis factor-alpha, transforming growth factor-beta 1, or interleukin 1 alpha/beta. We showed here that LBIF strongly inhibited the proliferation of various tumor cell lines irrespective of cell lineage or species. LBIF was effective on a wider spectrum of tumor cell lines than other cytokines tested here. The inhibition resulted from cytotoxic or cytostatic effects, depending on individual characteristics of tumor cell lines. Five cell lines showed insensitivity against LBIF activity, suggesting a plausible involvement of LBIF receptor molecules to transduce LBIF signals. These results suggest that LBIF may play important roles in regulating cell growth.

Cyclin D1 overexpression in rat two-stage bladder carcinogenesis and its relationship with oncogenes, tumor suppressor genes, and cell proliferation.

Overexpression of cyclin D1 has been implicated in the malignant transformation of a variety of human cancers, including urinary bladder carcinomas. However, few reports have addressed the significance of cyclin D1 overexpression in chemical carcinogenesis in rodents. In the present study, we evaluated the oncogenic potential of cyclin D1 in experimental rat urinary bladder carcinogenesis and its relationships to the oncogenes cyclin E, K-ras, and H-ras as well as tumor suppressor genes p53 and p21WAF1/Cip1. In addition, proliferation status of preneoplastic lesions and tumors was assessed by proliferating cell nuclear antigen immunohistochemistry. Fisher 344 rats were initiated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for 4 weeks and then administered 5% sodium L-ascorbate in diet. Animals were sacrificed at weeks 4, 8, 12, 18, and 24. Preneoplastic lesions such as papillary or nodular hyperplasia and neoplastic lesions of the urinary bladder were observed during carcinogenesis. By immunohistochemical examination, overexpression of cyclin D1 protein was observed in 17% of papillary or nodular hyperplasias, 66% of papillomas, and 69% of transitional cell carcinomas, whereas nuclear accumulation of p53 was observed in none of the preneoplastic lesions and in fewer than 2% of transitional cell carcinomas. Overexpression of cyclin D1 in preneoplastic lesions and tumors was not dependent on the size of the tumors or their proliferation status. Quantitation of mRNA in tumors by multiplex reverse transcription-PCR showed that average mRNA expression of cyclin D1 and cyclin E was increased, whereas average p21WAF1/Cip1 mRNA expression was decreased. More than 2-fold overexpression of cyclin D1 mRNA was observed in 50 and 60% of tumors at weeks 18 and 24, respectively. Localization of cyclin D1 mRNA expression was demonstrated by in situ hybridization, and the results were comparable to immunohistochemistry findings. None of the 25 tumors we examined by PCR-single-strand conformational polymorphism analysis harbored p53 mutations, H-ras mutations, or K-ras mutations. Thus, during the promotion phase of two-stage bladder carcinogenesis, overexpression of cyclin D1 in tumor cells may provide yet another mechanism by which tumors can gain a growth advantage. In contrast, tumors with mutated p53 may not have a growth advantage. Our results suggest that overexpression of cyclin D1 plays a critical role during urinary bladder carcinogenesis.

Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequences of cell-adhesive molecules.

We investigated that the antimetastatic and antiadhesive activities of peptides based on Arg-Gly-Asp adhesive signal in fibronectin could be augmented by their polymerization. Poly(Arg-Gly-Asp), which consists of a repetitive sequence of Arg-Gly-Asp, inhibited lung metastases in C57BL/6 mice more effectively than Arg-Gly-Asp tripeptide was able to do, when coinjected or separately injected with B16-BL6 cells. The adhesion of tumor cells to fibronectin was specifically inhibited by adding poly(Arg-Gly-Asp) but not unrelated peptides. In contrast, poly(Arg, Gly, Asp), in which three amino acids are randomly arranged, showed neither inhibition of lung metastases nor any adhesive ability to attach to tumor cells. The inhibitory effect of polymeric peptides containing the Arg-Gly-Asp sequence on lung metastases decreased according to the decreasing repeat units of the Arg-Gly-Asp core sequence. Polymeric peptides with Arg-Gly-Asp entrapped within the liposome membranes also caused a remarkable reduction of metastatic colonies. In a spontaneous metastasis model, multiple i.v. administrations of poly(Arg-Gly-Asp) after tumor inoculation caused the significant reduction of metastatic colonies in the lung but did not affect the growth (size) of primary tumor. We found that the polymerization (multivalency) of the Arg-Gly-Asp core sequence was able to augment the inhibition of tumor lung metastases in experimental and spontaneous metastasis models as well as the cell-adhesive property more effectively than a monovalent unit of Arg-Gly-Asp peptide.

Novel prognostic prediction models for patients with stage IV colorectal cancer after concurrent curative resection.

BACKGROUND: We developed a prediction tool for recurrence and survival in patients with stage IV colorectal cancer (CRC) following surgically curative resection. PATIENTS AND METHODS: From January 1983 to December 2012, 113 patients with CRC and synchronous liver and/or lung metastatic CRC were investigated at the Osaka Medical Center for Cancer and Cardiovascular Diseases. All patients underwent curative resection of primary and metastatic lesions. In the group of patients who underwent surgery from 1983 to 2008, a Cox regression model was used to develop prediction models for 1-year, 3-year and 5-year cancer-specific survival (CSS) and relapse-free survival (RFS). In the other group of patients who underwent surgery from 2009 to 2012, the developed prediction model was validated. RESULTS: Univariate analysis of clinicopathological factors showed that the following factors were significantly correlated with CSS and RFS: preoperative serum carcinoembryonic antigen level, tumour location, pathologically defined tumour invasion and lymph node metastasis, and synchronous metastatic lesions. Using these variables, novel prediction models predicting CSS and RFS were constructed using the Cox regression model with concordance indexes of 0.802 for CSS and 0.631 for RFS. The prediction models were validated by external data sets in an independent patient group. CONCLUSIONS: We developed novel and reliable personalised prognostic models, integrating tumour, node, metastasis (TNM) factors as well as the preoperative serum carcinoembryonic antigen level, tumour location and metastatic lesions, to predict patients' prognosis following surgically curative resection. This individualised prediction model may help clinicians in the treatment of postoperative stage IV CRC following surgically curative resection.

Inhibition of M-tropic HIV-1 infection by the fd phage-gene 3 protein with MIP-1alpha-binding activity.

CCR5 is a chemokine receptor with seven transmembrane-domains. It is expressed on T cells and macrophages and functions as the principal co-receptor for macrophage (M)-tropic strains of HIV-1. The anti-CCR5 monoclonal antibody (mAb) 2D7 inhibits the binding and chemotaxis of the three natural beta-chemokine ligands of CCR5, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES, to CCR5(+) cells. The mAb also efficiently blocks the infectivity of several M-tropic and dual-tropic HIV-1 strains in vitro. In this study, we attempted to determine the peptide motif recognized with the 2D7 mAb. We isolated phage clones by panning a phage display library using 2D7 and identified three peptide motifs. One of these phage clones (M23) showed a marked inhibitory activity on HIV-1 infection. The unique sequence of 15 amino acids with an internal disulfide bond was inserted in the g3p of the M23 phage clone (M23-g3p). The M23-g3p was purified by fast-performance liquid chromatography (FPLC). We show here that (1) M23-g3p was specifically recognized with anti-CCR5 mAb; (2) M23-g3p showed inhibitory activity on the infectivity of M-tropic but not T-tropic HIV-1 strains; (3) M23-g3p bound to MIP-1alpha, MIP-1beta, and RANTES but not MCP-1. These results suggested that the M23-g3p might mimic the CCR5-binding domain shared by beta-chemokines, MIP-1alpha, MIP-1beta, and RANTES as well as the HIV-1 infection.

Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms. RESULTS: Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, and one measure significantly deteriorated (i.e., median nerve FCV). At the study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated versus placebo group at the study conclusion. At the dose used, fidarestat was well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group. CONCLUSIONS: The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy.

Bone-Subtracted Spinal CT Angiography Using Nonrigid Registration for Better Visualization of Arterial Feeders in Spinal Arteriovenous Fistulas.

BACKGROUND AND PURPOSE: Pretreatment diagnosis for the location of shunts and arterial feeders of spinal arteriovenous fistulas is crucial. This study aimed to evaluate the utility of subtracted CT angiography imaging by using nonrigid registration (R-CTA) in patients with spinal arteriovenous fistulas compared with conventional CTA imaging. MATERIALS AND METHODS: The records of 15 consecutive subjects (mean age, 65 years; 2 women) who had undergone CTA and digital subtraction angiography for clinically suspected spinal arteriovenous fistula were reviewed. From CTA images obtained at the arterial and late arterial phases, warped images of the late arterial phase were obtained by using nonrigid registration that was adjusted to the arterial phase images. R-CTA images were then obtained by subtracting the warped images from the arterial phase images. The accuracies of using nonrigid registration and conventional spinal CTA and the time required for detecting arterial feeders in spinal arteriovenous fistulas were analyzed for each patient with DSA results as a standard reference. The difference between R-CTA and conventional spinal CTA was assessed by the Welch test and the McNemar χ(2) test. RESULTS: R-CTA had a higher accuracy compared with conventional spinal CTA (80% versus 47%, P = .025). The time for interpretation was reduced in R-CTA compared with conventional spinal CTA (45.1 versus 97.1 seconds, P = .002). CONCLUSIONS: Our subtracted CTA imaging by using nonrigid registration detects feeders of spinal arteriovenous fistulas more accurately and quickly than conventional CTA.