Neuroimaging biomarkers of glial activation for predicting the annual cognitive function decline in patients with Alzheimer's disease.

BACKGROUND: Glial activation is central to the pathogenesis of Alzheimer's disease (AD). However, researchers have not demonstrated its relationship to longitudinal cognitive deterioration. We aimed to compare the prognostic effects of baseline positron emission tomography (PET) imaging of glial activation and amyloid/tau pathology on the successive annual cognitive decline in patients with AD. METHODS: We selected 17 patients diagnosed with mild cognitive impairment or AD. We assessed the annual changes in global cognition and memory. Furthermore, we assessed the predictive effects of baseline amyloid and tau pathology indicated by cerebrospinal fluid (CSF) concentrations and PET imaging of glial activation (11C-DPA-713-binding potential in the area of Braak 1-3 [11C-DPA-713-BPND]) on global cognition and memory using a stepwise regression analysis. RESULTS: The final multiple regression model of annual changes in global cognition and memory scores included 11C-DPA-713-BPND as the predictor. The CSF Aß42/40 ratios and p-tau concentrations were removed from the final model. In stepwise Bayesian regression analysis, the Bayes factor-based model comparison suggested that the best model included 11C-DPA-713-BPND as the predictor of decline in global cognition and memory. CONCLUSIONS: Translocator protein-PET imaging of glial activation is a stronger predictor of AD clinical progression than the amount of amyloid/tau pathology measured using CSF concentrations. Glial activation is the primary cause of tau-induced neuronal toxicity and cognitive deterioration, thereby highlighting the potential of blocking maladaptive microglial responses as a therapeutic strategy for AD treatment.

Involvement of inflammation in the medial temporal region in the development of agitation in Alzheimer's disease: an in vivo positron emission tomography study.

BACKGROUND: The evaluation of 11 C-DPA-713 binding using positron emission tomography for quantifying the translocator protein can be a sensitive approach in determining the level of glial activation induced by neuroinflammation. Herein, we aimed to investigate the relationship between regional 11 C-DPA713-binding potential (BPND ) and neuropsychiatric symptoms (NPS) in amyloid-positive Alzheimer's disease (AD) patients. METHODS: Fifteen AD patients were enrolled in this study. Correlations were evaluated between the 11 C-DPA713-BPND and Neuropsychiatric Inventory Questionnaire (NPI-Q) scores, including scores in its four domains: agitation, psychosis, affective, and apathy. 11 C-DPA713-BPND values were compared between groups with and without the neuropsychiatric symptoms for which a relationship was observed in the abovementioned correlation analysis. RESULTS: A positive correlation was found between the severity of agitation and 11 C-DPA713-BPND in the Braak 1-3 area, including the amygdala, hippocampal and parahippocampal regions, and lingual and fusiform areas. An increase in the 11 C-DPA713-BPND was observed in AD patients with agitation. We did not find any significant effects of possible confounding factors, such as age, duration of illness, education, gender, Mini-Mental State Examination score, cerebrospinal fluid amyloid ß 42/40 ratio, and apolipoprotein E4 positivity, on either the 11 C-DPA713-BPND or agitation score. CONCLUSIONS: Neuroinflammation in the medial temporal region and its neighbouring area was shown to be associated with the development of agitation symptoms in AD patients. Our findings extend those of previous studies showing an association between some NPS and inflammation, suggesting that immunologically based interventions for agitation can serve as an alternative treatment for dementia.

Season of birth and vulnerability to the pathology of Alzheimer's disease: an in vivo positron emission tomography study.

BACKGROUND: This study used positron emission tomography to examine whether the seasonal birth effect as an exogenic indicator of early life environmental factors influenced vulnerability to Alzheimer's disease (AD) pathology in the elderly. METHODS: We analysed datasets from the Alzheimer's Disease Neuroimaging Initiative, which included the data for 234 cognitively normal (CN) individuals and patients with mild cognitive impairment (MCI) (n = 114) and AD dementia (n = 38). As an index of amyloid ß (Aß)/tau accumulation, the 18 F-AV-45- and 18 F-AV-1451-standardized uptake value ratios (SUVRs) were compared between groups of spring-to-summer births and fall-to-winter births by analysis of covariance. In addition, a multiple linear regression analysis was performed to determine whether the season of birth was a predictor of 18 F-AV-45 and/or 18 F-AV-1451 SUVRs, for which a difference was observed. RESULTS: Seasonal birth difference was a good predictor of 18 F-AV-1451 SUVR. We found that participants with a fall-to-winter birth showed lower 18 F-AV-1451 SUVRs than those with a spring-to-summer birth in both the CN and MCI/AD groups, after correcting for the effect of age, sex, years of education, and Alzheimer's Disease Assessment Scale cognitive subscale score, that could possibly affect tau accumulation. CONCLUSIONS: Participants with a fall-to-winter birth showed less tau accumulation than those with a spring-to-summer birth after accounting for the factors that could affect tau accumulation. Our findings showed a vulnerability to tau pathology in participants with a fall-to-winter birth, which may be caused by perinatal or postnatal brain damage due to the risk factors associated with the cold season.

Significant effects of cholinesterase inhibitors on tau pathology in the Alzheimer's disease continuum: An in vivo positron emission tomography study.

OBJECTIVES: No prior study has assessed the effects of cholinesterase inhibitors (ChEIs) on tau pathology in the brains of patients with Alzheimer's disease (AD). Using positron emission tomography, this study aimed to investigate whether ChEIs reduce tau aggregation in amyloid-positive participants. METHODS: We analyzed datasets from the Alzheimer's Disease Neuroimaging Initiative and included amyloid-positive participants who had undergone baseline and 1- or 2-year follow-up AV-1451 positron emission tomography scans. We included participants treated with and without ChEIs (ChEIs group: n = 15, No-ChEIs group, n = 45). The annual change in tau aggregation was calculated as the difference in AV-1451- standardized uptake value ratio (SUVR) between the two scans divided by the time between scans. Group differences in annual AV-1451-SUVR change were examined. RESULTS: We found a significantly lower annual change in AV-1451-SUVR in the Braak 1/2 regions (entorhinal cortex and hippocampus) of participants taking ChEIs. Increased AV-1451-SUVR between the first and second examinations were observed in 22 of 45 participants not taking ChEIs and 2 of 15 participants taking ChEIs. Fisher's exact test showed a significant difference in the ratio of participants with increased AV-1451-SUVR between the groups. CONCLUSIONS: The findings of this positron emission tomography study suggest that the administration of ChEIs has some neuroprotective effects in patients of the AD continuum, at least in the early stage of the disease progression. This in vivo effect may be mediated via tau, preventing amyloid ß-induced neurotoxicity.

Relationship between neuropsychiatric symptoms and Alzheimer's disease pathology: An in vivo positron emission tomography study.

OBJECTIVES: To investigate the relationship between amyloid-ß- and tau-based Alzheimer's disease (AD) pathologies assessed using positron emission tomography imaging and neuropsychiatric symptoms (NPS) in a sample of AD continuum including clinically normal subjects and patients with mild cognitive impairment or AD. METHODS: We analyzed datasets of the Alzheimer's disease Neuroimaging Initiative and included amyloid-positive subjects who underwent an AV-45 scan within 1 year of an AV-1451 scan (n = 99). Correlation between standardized uptake value ratio (SUVR) of AV-45 and AV-1451 and the Neuropsychiatric Inventory (NPI) score (and its four domain subscores for hyperactivity, psychosis, affective, and apathy) was evaluated. Stepwise logistic regression analysis was used to examine the influence of SUVRs on the presence of NPS. SUVRs were also tested for their ability to discriminate the group with NPS using receiver operating characteristic (ROC) curve analyses. RESULTS: Significant positive relationships were found between the total NPI score and affective symptoms and Braak 1&2 (transentorhinal region) AV-1451 SUVR. Stepwise logistic regression analysis identified tau accumulation in the area of Braak 1&2 as a significant covariate discriminating the presence of affective symptoms. The area under the ROC curve analysis showed that subjects with affective symptoms were discriminated by AV-1451 SUVR with an accuracy of 77.7%. CONCLUSIONS: Tau aggregation in the transentorhinal region, where neurodegeneration affected by tau pathology was seen in the early stage of AD, correlated with more severe NPS, especially affective symptoms. Therefore, tau pathology in the transentorhinal cortex might be associated with affective symptoms in the early stage of AD.

Interaction effect of Alzheimer's disease pathology and education, occupation, and socioeconomic status as a proxy for cognitive reserve on cognitive performance: in vivo positron emission tomography study.

AIM: Educational attainment, occupation, and socioeconomic status have been regarded as major factors influencing cognitive reserve (CR). This study aimed to investigate the interaction effect of amyloid-ß/tau burden and education/occupation/socioeconomic status as a proxy for CR on cognitive performance. METHODS: We analyzed the datasets of the Alzheimer's Disease Neuroimaging Initiative. We included clinically normal subjects and patients with mild cognitive impairment or Alzheimer's disease who had undergone a florbetapir scan within 1 year of a flortaucipir (AV-1451) scan (n = 127). Partial correlation analysis between the standardized uptake value ratio of florbetapir/AV-1451 and the proxy for CR was performed with the 13-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) score as a covariate. Stepwise multiple linear regression analysis was performed to determine the predictors of ADAS-cog performance based on the interaction between the imaging biomarkers and the proxy for CR. RESULTS: We found a significant positive partial correlation between educational level and tau pathology in Braak stage 1/2 areas, and we observed significantly higher tau accumulation among participants with higher education when ADAS-cog score was used as a covariate. The interaction between tau and education was a good predictor of cognitive function, with higher tau accumulation showing a greater association with higher ADAS-cog score among participants with less education than among those with more education. CONCLUSION: Our findings indicate the protective effect of education against cognitive dysfunction in early-stage Alzheimer's disease pathology and suggest that education may exert a beneficial effect by reducing the adverse cognitive consequences of tau aggregation.

Trait-anxiety and glial-related neuroinflammation of the amygdala and its associated regions in Alzheimer's disease: A significant correlation.

Background: Positron emission tomography, which assesses the binding of translocator protein radiotracers, 11C-DPA-713, may be a sensitive method for determining glial-mediated neuroinflammation levels. This study investigated the relationship between regional 11C-DPA713 binding potential (BPND) and anxiety in patients with Alzheimer's disease (AD) continuum. Methods: Nineteen patients with AD continuum determined to be amyloid-/p-tau 181-positive via cerebrospinal fluid analysis were included in this cross-sectional study (mild cognitive impairment [MCI, n = 5] and AD [n = 14]). Anxiety was evaluated using the State-Trait Anxiety Inventory (STAI). A whole-brain voxel-based analysis was performed to examine the relationship between 11C-DPA-713-BPND values at each voxel and the STAI score. Stepwise multiple regression analysis was performed to determine the predictors of STAI scores using independent variables, including 11C-DPA-713-BPND values within significant clusters. 11C-DPA-713-BPND values were compared between patients with AD continuum with low-to-moderate and high STAI scores. Results: Voxel-based analysis revealed a positive correlation between trait anxiety severity and 11C-DPA713-BPND values in the centromedial amygdala and the left inferior occipital area [P < 0.001 (uncorrected) at the voxel-level]. 11C-DPA713-BPND values in these regions were a strong predictor of the STAI trait anxiety score. Specifically, patients with AD continuum and high trait anxiety had increased 11C-DPA713-BPND values in these regions. Conclusions: The amygdala-occipital lobe circuit influences the control of emotional generation, and disruption of this network by AD pathology-induced inflammation may contribute to the expression of anxiety. Our findings suggest that suppression of inflammation can help effectively treat anxiety by attenuating damage to the amygdala and its associated areas.

Twelve-year results of a direct-bonded partial prosthesis in a patient with advanced periodontitis: a clinical report.

Prosthodontic treatment for patients with advanced periodontitis is a therapeutic challenge. A minimally invasive technique is preferred to preserve the remaining mobile abutment teeth. This report describes the initial clinical treatment and 12-year follow-up of a direct-bonded prosthesis reinforced with a cast metal framework, used as a conservative treatment option to replace periodontally involved maxillary lateral incisors.

Kinetic modeling and non-invasive approach for translocator protein quantification with 11C-DPA-713.

INTRODUCTION: 11C-DPA-713 is a positron emission tomography (PET) radiotracer developed for imaging the expression of the translocator protein (TSPO) in glial cells, which is considered to be a marker of the neuroinflammatory burden. This study investigated the pharmacokinetic profile of 11C-DPA-713 and evaluated kinetic modeling and non-invasive TSPO quantification using dynamic PET imaging data in the Alzheimer's disease (AD) and cognitive normal (CN) participants. METHODS: Eleven patients with AD and 6 CN participants were examined using dynamic 11C-DPA-713 PET imaging for 60 min with arterial blood sampling. Time-activity curves were calculated from the cerebellum and three composite regions of interest (ROIs), according to the anatomical definitions of Braak's stages 1 to 3, stage 4, stage 5, and stage 6 that correspond to the pathological stages of tangle deposition. The total distribution volume (VT) was evaluated using compartmental modeling and graphical analysis. Reference region-based methods were implemented using an optimal area that was assumed to be void of the radiotracer target as reference tissue. RESULTS: The concentration of radioactivity in plasma demonstrated rapid clearance. 11C-DPA-713 peaked rapidly in the gray matter. Compartmental modeling resulted in a good fit, and the one-tissue model with estimated blood volume correction (1Tv) showed the best performance. The estimated VT obtained from the graphical plasma methods was highly correlated with that obtained from 1Tv. Reference region-based analysis was conducted using the Braak 6 area as the reference region, and the estimated non-displaceable binding potential was highly correlated with that obtained from 1Tv. CONCLUSION: 11C-DPA-713 possesses properties suitable for TSPO quantification with PET imaging. The Braak 6 area was shown to be a useful reference region in the patients with AD and the CN participants, and non-invasive reference tissue models using the Braak 6 area as a reference region can be employed for TSPO quantification with 11C-DPA-713-PET imaging as an alternative to the invasive compartmental model.

Estimation of blood-based biomarkers of glial activation related to neuroinflammation.

Background: Neuroinflammation is a well-known feature of Alzheimer's disease (AD), and a blood-based test for estimating the levels of neuroinflammation would be expected. In this study, we examined and validated a model using blood-based biomarkers to predict the level of glial activation due to neuroinflammation, as estimated by 11C-DPA-713 positron emission tomography (PET) imaging. Methods: We included 15 patients with AD and 10 cognitively normal (CN) subjects. Stepwise backward deletion multiple regression analysis was used to determine the predictors of the TSPO-binding potential (BPND) estimated by PET imaging. The independent variables were age, sex, diagnosis, apolipoprotein E4 positivity, body mass index and the serum concentration of blood-based biomarkers, including monocyte chemotactic protein 1 (MCP-1), fractalkine, chitinase 3-like protein-1 (CHI3L1), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and clusterin. Results: Sex, diagnosis, and serum concentrations of MCP1 and sTREM2 were determined as predictors of TSPO-BPND in the Braak1-3 area. The serum concentrations of MCP1 and sTREM2 correlated positively with TSPO-BPND. In a leave one out (LOO) cross-validation (CV) analysis, the model gave a LOO CV R2 of 0.424, which indicated that this model can account for approximately 42.4% of the variance of brain TSPO-BPND. Conclusions: We found that the model including serum MCP-1 and sTREM2 concentration and covariates of sex and diagnosis was the best for predicting brain TSPO-BPND. The detection of neuroinflammation in AD patients by blood-based biomarkers should be a sensitive and useful tool for making an early diagnosis and monitoring disease progression and treatment effectiveness.

Effects of metal primers on the bonding of an adhesive resin cement to noble metal ceramic alloys after thermal cycling.

STATEMENT OF PROBLEM: Although the effectiveness of primers for resin bonding to noble alloys has been demonstrated, no effective clinical technique for bonding to noble metal ceramic alloys has been established. PURPOSE: The purpose of this study was to evaluate the effects of metal primers on the shear bond strength of an adhesive resin to noble metal ceramic alloys after thermal cycling. MATERIAL AND METHODS: Sixty-three disk-shaped specimens (10 × 2.5 mm) were cast from high-gold-content alloys (Super Metal W-85: W85 or IFK88 GR: IFK88), a high-palladium-content alloy (Super Metal N-40: N40), and an Ag-Pd-Cu-Au alloy (Castwell M.C.12: MC12). Smaller-sized disk-shaped specimens (8 × 2.5 mm) were fabricated with MC12. Bonding surfaces were finished with 600-grit SiC-paper and airborne-particle abraded with 50-µm alumina. Pairs of disks were primed (V-Primer: VP; ML Primer: ML; or Metaltite: MT) and bonded with an adhesive resin (Super-Bond C&B). The bond strengths were determined before and after 20,000 and 50,000 thermal cycles (n=7). Data were analyzed by using a 3-way ANOVA and the Bonferroni test (α=.05). Failure modes were determined by optical microscope and SEM observation. RESULTS: Bond strengths to high-gold-content alloys with VP and MT significantly decreased after the thermal cycling (P<.001). Bond strengths to W85 (35.27 ±4.25 MPa) and IFK88 (33.57 ±3.56 MPa) after 50,000 thermal cycles obtained by ML were the highest (P<.001), and these groups showed combination failures. Bond strengths to N40 significantly decreased after 50,000 thermal cycles (P<.001), regardless of primers. CONCLUSIONS: Shear bond strengths (SBS) to high-gold-content alloys were not degraded up to 50,000 thermal cycles when primed with ML. None of the primers evaluated was effective for high-palladium-content alloy.

Evaluation of the effects of three pretreatment conditioners and a surface preparation system on the bonding durability of composite resin adhesive to a gold alloy.

This study aimed to evaluate the effect of three pretreatment conditioners and surface preparations on a composite resin adhesive for a gold alloy. Cast disk specimens were made and bonded with RelyX Unicem luting agent under six surface conditions: 1) polished with No.600 carbide paper, 2) air-abraded with alumina, 3) Alloy Primer metal conditioner was applied after alumina-abrasion, 4) Monobond Plus multipurpose conditioner was applied after alumina-abrasion, 5) M. L. Primer metal conditioner was applied after alumina-abrasion, and 6) Rocatec multipurpose silica-coating system was applied. The bond strengths were determined before and after thermocycling (50,000 cycles). The bond strengths of the alumina-abrasion group were significantly decreased after thermocycling. The Rocatec and M. L. Primer exhibited higher bond strengths than other treatments. The application of metal conditioners and multipurpose surface preparations was recommended for improved bonding between the evaluated adhesive resin and gold alloy.

Strongyloides stercoralis colitis in a patient positive for human T-cell leukaemia virus with rheumatoid arthritis during an anti-rheumatic therapy: a case report.

An elderly woman with rheumatoid arthritis (RA) presented with a chief complaint of abdominal pain and diarrhoea while undergoing treatment with low-dose corticosteroids and abatacept. Endoscopic and histopathological findings revealed manifestations of ulcerative colitis (UC). An intermediate dose of corticosteroids and 5-aminosalicylic acid were administered. Abatacept was discontinued; the anti-TNF biologic, golimumab, was administered for treatment of both RA and UC. However, colitis worsened in response to this therapeutic regimen. Colonoscopy revealed severe mucosal lesions; larvae were detected in samples taken from multiple shallow mucosal ulcers. The patient was diagnosed with Strongyloides stercoralis colitis based on the results of an anti-parasite antibody test and examination of the larval DNA. Furthermore, serology revealed a positive test for antibodies against human T-cell leukaemia virus type 1 (HTLV-1). Immunosuppressive treatment was terminated; ivermectin was administered, which resulted in improvements in colitis symptoms within a few weeks. There are several published reports describing S. stercoralis colitis as a lethal mimic of UC. Corticosteroid and anti-TNF therapies have been reported as among the major risk factors associated with strongyloidiasis in patients with HTLV-1 infection. Therefore, HTLV-1 and Strongyloides infections may be considered in cases of new-onset gastrointestinal symptoms during immunosuppressive therapy, particularly in HTLV-1-endemic regions.

Comparison of dimension reduction methods on fatty acids food source study.

Serum fatty acids (FAs) exist in the four lipid fractions of triglycerides (TGs), phospholipids (PLs), cholesteryl esters (CEs) and free fatty acids (FFAs). Total fatty acids (TFAs) indicate the sum of FAs in them. In this study, four statistical analysis methods, which are independent component analysis (ICA), factor analysis, common principal component analysis (CPCA) and principal component analysis (PCA), were conducted to uncover food sources of FAs among the four lipid fractions (CE, FFA, and TG + PL). Among the methods, ICA provided the most suggestive results. To distinguish the animal fat intake from endogenous fatty acids, FFA variables in ICA and factor analysis were studied. ICA provided more distinct suggestions of FA food sources (endogenous, plant oil intake, animal fat intake, and fish oil intake) than factor analysis. Moreover, ICA was discovered as a new approach to distinguish animal FAs from endogenous FAs, which will have an impact on epidemiological studies. In addition, the correlation coefficients between a published dataset of food FA compositions and the loading values obtained in the present ICA study suggested specific foods as serum FA sources. In conclusion, we found that ICA is a useful tool to uncover food sources of serum FAs.

Effects of metal primers on bonding of adhesive resin cement to noble alloys for porcelain fusing.

This study evaluated the effects of metal primers on the bonding of adhesive resin to four pure metals (Au, Pd, Ag, Cu) and two noble alloys for porcelain fusing (high-gold and high-palladium content alloys). Bonding surface was polished with 600-grit silicon carbide paper and primed with one of the three metal primers (V-Primer, Metaltite, and M.L. Primer). Bonded specimens were fabricated by applying adhesive resin (Super-Bond C&B) on the primed surface. Shear bond strength (SBS) was determined both before and after thermocycling (4-60 degrees C for 2,000 cycles). The highest SBS values to each pure metal after thermocycling were 33.5 MPa for Au by M.L. Primer, 35.0 MPa for Ag by V-Primer, and 34.4 MPa for Cu by Metaltite. SBS to high-gold content alloy after thermocycling was 33.3 MPa by M.L. Primer. None of the primers was effective for pure Pd and high-palladium content alloy after thermocycling.

Multivariate Analysis for Molecular Species of Cholesteryl Ester in the Human Serum.

Cholesteryl ester (CE) is an ester of cholesterol and fatty acid (FA). Plasma CE reflects complicated metabolisms of cholesterol, phospholipids, lipoproteins, and dietary FAs. An informatics approach could be useful for analysis of the CE species. In this study, two basic dimension reduction methods, principal component analysis (PCA) and factor analysis, were applied to serum CE species determined by LC-MS/MS in a Japanese population (n = 545). PCA and factor analysis both reflected the size (concentration), food source, fat solubility, and biological aspect of the CE species. In a comparison between PCA (PC4) and factor analysis (factor 4), the latter was found to be more suggestive from a biological aspect of n-6 FAs. Cholesteryl docosahexaenoate (DHA) was found to be unique by a factor analysis, possibly relevant to the unique accumulation of DHA in the brain. An informatics approach, especially factor analysis, might be useful for the analysis of complicated metabolism of CE species in the serum.

Binding of AlF-C, an Orc1-binding transcriptional regulator, enhances replicator activity of the rat aldolase B origin.

A region encompassing the rat aldolase B gene (aldB) promoter acts as a chromosomal origin of DNA replication (origin) in rat aldolase B-nonexpressing hepatoma cells. To examine replicator function of the aldB origin, we constructed recombinant mouse cell lines in which the rat aldB origin and the mutant derivatives were inserted into the same position at the mouse chromosome 8 by cre-mediated recombination. Nascent strand abundance assays revealed that the rat origin acts as a replicator at the ectopic mouse locus. Mutation of site C in the rat origin, which binds an Orc1-binding protein AlF-C in vitro, resulted in a significant reduction of the replicator activity in the mouse cells. Chromatin immunoprecipitation (ChIP) assays indicated that the reduction of replicator activity was paralleled with the reduced binding of AlF-C and Orc1, suggesting that sequence-specific binding of AlF-C to the ectopic rat origin leads to enhanced replicator activity in cooperation with Orc1. Involvement of AlF-C in replication in vivo was further examined for the aldB origin at its original rat locus and for a different rat origin identified in the present study, which contained an AlF-C-binding site. ChIP assays revealed that both replication origins bind AlF-C and Orc1. We think that the results presented here may represent one mode of origin recognition in mammalian cells.

Correlation between angiogenesis and p53 expression in lung adenocarcinoma of young patients.

Lung cancer commonly occurs in individuals who are 60 years of age or older. Lung cancer in patients younger than 40 years of age is rare and is often advanced when discovered. However, the biological features of lung cancer in young adults have not yet been fully elucidated. This study was conducted to determine the role of p53 expression and neoangiogenesis in lung adenocarcinomas of young patients. Lung adenocarcinomas, which were surgically resected from 20 patients younger than 40 years of age between 1977 and 1996, were compared with lung adenocarcinomas selected with random sampling from 45 patients older than 60 years of age. The expression of p53, vascular endothelial growth factor (VEGF), CD34, a marker for vascular endothelial cells, and proliferating cell nuclear antigen (PCNA) were studied immunohistochemically in both young and elderly patient groups. Lung adenocarcinomas with p53-positive staining showed higher expression of VEGF protein than p53-negative tumors in both the young and the elderly groups. However, the intratumoral microvessel count was significantly higher in the p53-positive young group than in the elderly group. The percentage of VEGF-positive cells correlated significantly with intratumoral microvessel counts in the young group. The survival rate tended to be poorer in patients with a high VEGF labeling index and p53-positive staining than in other young patients. Lung adenocarcinoma occurring in young patients tends to have a poorer prognosis, and angiogenesis of lung adenocarcinoma in young patients is more closely correlated with p53 expression than in elderly patients.

Effect of fiber-premixed indirect resin composite substructure on fracture resistance of MOD composite inlays adhered with two different adhesive resin cements.

This study evaluated the effect of a fiber-premixed indirect resin composite (FMC) substructure on the fracture resistance of mesialocclusal-distal (MOD) indirect composite restorations adhered to extracted human upper premolars. The teeth received a standardized MOD cavity preparation, and indirect composite inlays were fabricated with or without using the FMC. Inlays were cemented into the cavity preparations using either Super-Bond C&B or Panavia F2.0. A total of 28 specimens, namely seven specimens for four groups, were thus fabricated. Failure load and failure energy were determined after thermocycling (4-60 degrees C for 5,000 cycles). In terms of failure load, no significant differences were found among the four groups. In terms of failure energy, FMC substructure exerted a significantly favorable effect on Super-Bond C&B-bonded group but a negative one on Panavia F2.0-bonded group. In conclusion, the failure energy of the group using FMC substructure and which was adhered using Super-Bond C&B was significantly higher than the other groups.

Induction chemotherapy with cisplatin, vinorelbine, and mitomycin-C followed by surgery for patients with pathologic N2 non-small-cell lung cancer.

PURPOSE: The treatment strategy for patients with non-small-cell lung cancer (NSCLC) involving ipsilateral mediastinal lymph nodes is still controversial. We performed a phase II feasibility study of induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC. PATIENTS AND METHODS: Patients with mediastinoscopy- positive stage IIIA N2 NSCLC received 2 cycles of cisplatin 80 mg/m2, vinorelbine 25 mg/m2, and mitomycin-C 8 mg/m2. Patients without progressive disease underwent thoracotomy and lobectomy with lymph node dissections 2-4 weeks later. RESULTS: From January 2000 to July 2004, 24 eligible patients (15 men, 9 women) were enrolled. Induction chemotherapy was completed as planned in 23 patients (95.8%). Hematological toxicity was the primary grade 3/4 toxicity. Twelve (50%) patients achieved a partial response. Twenty-three patients underwent surgical resection, and complete resection was achieved in 22 patients (95.7%). There were no surgery-related deaths. Pathologic complete response in metastatic lymph nodes was achieved in 5 patients. With a median follow-up of 5.4 years (range, 2.88-7.7 years), the estimated 5-year survival was 51.8% (95% CI, 41.3-62.3) and progression-free survival was 46.6% (95% CI, 36-57.2). CONCLUSION: Induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC was feasible and associated with high response to lymph node metastasis and good survival.