Multiperiodic magnetoplasmonic gratings fabricated by the pulse force nanolithography.

We propose a novel, to the best of our knowledge, technique for magnetoplasmonic nanostructures fabrication based on the pulse force nanolithography method. It allows one to create the high-quality magnetoplasmonic nanostructures that have lower total losses than the gratings made by the electron-beam lithography. The method provides control of the surface plasmon polaritons excitation efficiency by varying the grating parameters such as the scratching depth or the number of scratches in a single period. The quality of the plasmonic gratings was estimated by means of the transverse magneto-optical Kerr effect that is extremely sensitive to the finesse of a plasmonic structure.

Resonances of the magneto-optical intensity effect mediated by interaction of different modes in a hybrid magnetoplasmonic heterostructure with gold nanoparticles.

Here we demonstrate a novel magnetoplasmonic heterostructure for efficient control of light. It consists of gold nanoparticles embedded in a thin magnetic film covered with a gold layer pierced with periodic nanoslit array. Unique feature of the proposed structure is that it supports four different types of optical modes in the same frequency range including localized and propagating surface plasmons along with waveguide modes. A peculiar magneto-optical response appears at the frequencies of the mode hybridization. The most important result comes from hybridization of the localized and propagating plasmons leading to a significant increase of the magneto-optical effect intensity.

Tailoring of the carbon nanowall microstructure by sharp variation of plasma radical composition.

In this paper we propose a new and simple method to tune the carbon nanowall microstructure by sharp variation of CH4/H2 plasma conditions. Using theoretical calculations we demonstrated that the sharp variation of gas pressure and discharge current leads to significant variation of plasma radical composition. In some cases such perturbation creates the necessary conditions for the nucleation of smaller secondary nanowalls on the surface of primary ones.

Identification of differentially expressed genes in prostatic epithelium in relation to androgen receptor CAG repeat length.

The CAG repeat within exon 1 of the androgen receptor (AR) has been associated with the development of prostate cancer. The shorter number of glutamine residues in the protein has been associated with a higher transcriptional activity of the AR and increased relative risk for prostate cancer. In an attempt to identify differentially expressed genes in prostate cancer in relation to AR CAG repeat length variation, in this study we used total mRNA from normal and tumor tissues from 2 prostate cancer patients with AR alleles containing 19 and 26 CAG repeats to perform differential-display RT-PCR analysis. We were able to identify 48 different transcripts that showed homology to several known genes associated with different biological pathways. Among the differentially expressed genes, ATRX and SFRP1 were further validated by quantitative RT-PCR. The transcripts of both ATRX and SFRP1 genes proved to be down-regulated in most of the prostate tumors analyzed by quantitative RT-PCR. Hypermethylation of the promoter region of the SFRP1 gene was found in 17.5% (7/40) of the cases analyzed and was associated with the loss of SFRP1 expression (p=0.014). The differentially expressed genes identified in this study are implicated in several cellular pathways that, when up- or down-regulated, might play a role in the tumorigenic process of the prostate.

Altered patterns of MDM2 and TP53 expression in human bladder cancer.

BACKGROUND: The TP53 gene maps to the short arm of chromosome 17 (17p13.1) and encodes for a nuclear phosphoprotein of 53 kd (p53) involved in cell cycle control. The MDM2 gene is located on the long arm of chromosome 12 (12q13-14), and it encodes for a nuclear protein (Mdm2) of 90 kd of molecular mass. Genetic alterations in the TP53 gene have been reported as frequent events in bladder cancer and are associated with disease progression. The MDM2 gene has been shown to be amplified and overexpressed in sarcomas; however, these changes have not yet been analyzed in neoplastic lesions of the urinary bladder. PURPOSE: We undertook the present study in order to determine the frequency of MDM2 and TP53 abnormalities in bladder tumors, as well as to examine the clinical relevance of identifying their altered patterns of expression in patients affected with bladder cancer. METHODS: We analyzed a cohort of 87 patients affected by bladder tumors. Altered patterns of expression of Mdm2 proteins were determined using an immunohistochemical assay with monoclonal antibody 2A10, and MDM2 gene amplifications were studied by Southern blotting. Mutant p53 proteins were identified using monoclonal antibody PAb1801. The presence of intragenic mutations in the TP53 gene were assessed utilizing single-strand conformation polymorphism and further characterized by sequencing. Associations were assessed statistically by the two-tailed Fisher's exact test. RESULTS: Twenty-six of 87 cases had abnormally high levels of Mdm2 proteins; however, only one case showed an MDM2 amplification. Thirty-six of 87 cases displayed p53 nuclear overexpression. Sixteen cases had abnormally high levels of both Mdm2 and p53 proteins. There was a strong statistical association between Mdm2 and p53 overexpression (Fisher's exact test: P = .018). Moreover, there was a striking association between Mdm2 overexpression and low-stage, low-grade bladder tumors (Fisher's exact test: P = .0005). CONCLUSIONS: The results suggest that aberrant Mdm2 and p53 phenotypes are frequent events in bladder cancer and may be involved in tumorigenesis or tumor progression in urothelial neoplasias. IMPLICATIONS: This study is the first to report altered patterns of MDM2 expression in human bladder tumors and demonstrates that aberrant Mdm2 and p53 phenotypes may be important diagnostic and prognostic markers in patients affected by bladder cancer.

Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression.

BACKGROUND: Approximately one third of the patients with superficially infiltrative transitional cell (T1-TNM pathological staging system) bladder carcinoma who are treated with transurethral resection alone have disease progression. Despite precise pathologic staging and grading, clinical outcome in these patients is not predictable. Recent reports reveal that mutations of the p53 tumor suppressor gene (also known as TP53) occur commonly in bladder cancers. PURPOSE: The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein product(s) of the mutated p53 tumor suppressor gene are associated with tumor progression in patients with T1 bladder cancer. METHODS: We examined deparaffinized tumor tissue specimens from transurethral resection in 43 patients with T1 bladder cancer who had not received adjuvant therapy. Nuclear overexpression of p53 protein was detected by immunohistochemical analysis using the mouse monoclonal antibody PAb1801, which stains both wild-type and mutant p53 proteins. The data were then correlated with the following conventional prognostic variables: age, sex, histologic presence of associated carcinoma in situ, and vascular invasion of tumor. Disease progression rates per 100 person-years were calculated. RESULTS: Median follow-up was 119 months. None of the urothelial and stromal cells from normal bladder specimens showed nuclear overexpression of p53 protein, but patients with T1 bladder tumors could be stratified into two groups with different patterns of staining for p53 protein. Eighteen patients (42%) had no more than 20% tumor cells with positive nuclear staining (group A), while the remaining 25 patients (58%) had 20% or more tumor cells with nuclear immunoreactivity (group B). Patients in group B had a significantly lower progression-free interval (P < .001). Disease progression rates were 20.5% per year for group B and 2.5% for group A. CONCLUSION: These results suggest that T1 bladder cancers exhibiting nuclear overexpression of p53 protein have a higher probability of disease progression. This study also suggests that p53 overexpression is an important prognostic factor in these patients and may be useful in selecting appropriate therapy. IMPLICATIONS: Large prospective studies are needed to confirm these results and to evaluate nuclear overexpression of p53 protein as a prognostic marker in bladder cancer.

Association between adherence, treatment satisfaction and illness perception in hypertensive patients.

The relationship between adherence to antihypertension medications, treatment satisfaction and illness perception has not been studied so far. The primary objective of this study was to examine the association between adherence to medication, treatment satisfaction and illness perception in Lebanese hypertensive patients. The relation between medication adherence and blood pressure (BP) control was also assessed. In this cross-sectional study, patients were recruited from the physician's practice offices and community pharmacies in Beirut. Patients who had been treated for hypertension for at least 3 months were invited to participate in the study; they completed three questionnaires: the 8-item Morisky Medication Adherence Scale (MMAS-8), the Treatment Satisfaction Questionnaire for Medication (TSQM-4) and the Brief Illness Perception Questionnaire (BIPQ). BP was also measured and recorded. A total of 117 subjects were included, of whom 29.1% had poor adherence to their antihypertension treatment (MMAS-8 scores<6). The odds of having well-controlled hypertension was 3.5 times higher in patients with high adherence compared with patients with poor adherence (P=0.010). Treatment satisfaction was significantly greater in patients with good adherence (P<0.001). Neither socio-demographic, disease- nor drug-related characteristics of the participants were significantly associated with medication adherence. As for illness perception, even though the mean BIPQ score of adherent participants was lower than the mean score of non-adherent participants, this difference did not reach statistical significance. In conclusion, treatment satisfaction was found to be a predictor of adherence. Studies are needed to determine whether interventions to increase satisfaction can improve adherence and BP control.

Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for survival of patients treated with M-VAC with 5-year follow-up.

PURPOSE: To determine survival in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and to analyze prechemotherapy and postchemotherapy factors for prognostic significance. PATIENTS AND METHODS: The survival of 111 patients with T2-4N0M0 bladder cancer treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was assessed. Prechemotherapy and postchemotherapy factors were analyzed for correlation with survival. Factors found to be significant on univariate analysis were subjected to multivariate analysis using Cox's proportional hazards model. RESULTS: The median follow-up duration was 5.3 years. Initial tumor (T) stage (P = .0001), presence of ureteral obstruction (P = .0074), and presence of a palpable mass (P = .0039) were the only pretreatment factors found to be significant on univariate analysis. Postchemotherapy surgery was performed in 81 patients. In these cases, postchemotherapy clinical stage and pathologic stage were significant factors on univariate analysis. In the multivariate analysis, the initial prechemotherapy T stage and the postchemotherapy pathologic stage (pT stage) were the only two factors to demonstrate independent significance. An association between downstaging postchemotherapy and survival was observed for patients with extravesical disease (T < or = 3B) at the start of treatment. In this subset, the 5-year survival rate was 54% for patients with downstaging versus 12% for those without downstaging. This association was not observed for patients with bladder-confined disease (T < or = 3A) at presentation. CONCLUSION: The stage of bladder cancer at presentation and at postchemotherapy pathologic staging are independent prognostic factors for long-term survival in patients treated with neoadjuvant chemotherapy. Downstaging after neoadjuvant chemotherapy was associated with improved survival in patients with muscle-invasive bladder cancers, but only for those with extravesical disease (T > or = 3B) pretreatment. Randomized comparisons will be required to assess the impact of chemotherapy on overall survival.

p53 nuclear overexpression: an independent predictor of survival in lymph node--positive colorectal cancer patients.

PURPOSE: This study was performed to determine the prognostic significance of p53 gene overexpression in a homogeneous group of node-positive colorectal cancer patients. MATERIALS AND METHODS: Paraffin sections from the primary tumors in 107 colorectal cancer patients who had preoperative serum carcinoembryonic antigen (CEA) levels less than five were examined for the expression of p53 nuclear protein by immunohistochemical staining using the monoclonal antibody PAb 1801. The nuclear p53 overexpression was compared with clinicopathologic variables and follow-up data. RESULTS: Positive staining was not observed in normal colorectal mucosal cells. Specific p53 nuclear staining was detected in primary tumor from 50 patients (46.7%). p53 nuclear overexpression was not significantly correlated with patients' sex, age, tumor location, differentiation, T stage, N stage, and lymphatic and/or vascular vessel invasion. With a median follow-up of 61.7 months, 60% of the p53-positive patients have had disease recurrence, versus only 35% of the p53-negative group (P = .02). Forty-two percent of the p53-positive patients died of colorectal cancer compared with 21.1% of the p53-negative patients (P = .03). By multivariate analysis, p53 overexpression was found to be an independent predictor for disease-free and disease-specific survival. CONCLUSION: In node-positive colorectal cancer patients with low preoperative CEA levels, nuclear p53 overexpression as determined by immunohistochemistry on archived tissue is an independent predictor for prognosis.

Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC.

PURPOSE: This study sought to examine the prognostic role of p53 nuclear overexpression in muscle-invasive bladder cancer because of its correlation with progression of superficial bladder cancer. PATIENTS AND METHODS: Ninety of 111 patients treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with a median follow-up duration of 5.8 years were evaluated. p53 nuclear overexpression was determined by immunohistochemistry on deparaffinized tissue sections. Patients were stratified into two groups according to the percent of tumor cells with positive nuclear reactivity. Overexpression was defined as tumors with > or = 20% cells with positive nuclear reactivity and nonoverexpression as tumors with less than 20% reactivity. RESULTS: Nuclear overexpression was observed in 47 patients and nonoverexpression in 43 patients. Patients whose tumors had p53 overexpression had a significantly higher proportion of cancer deaths. A multivariate analysis that evaluated the pretreatment variables p53 nuclear overexpression, age, sex, palpable mass, prechemotherapy tumor stage, performance status, ureteral obstruction, tumor size, multifocality, and grade showed that p53 overexpression had independent significance for survival (P = .001; relative risk ratio, 3.1). The impact of p53 overexpression on survival was predominantly in T2 and T3a tumors. Long-term survival was evident in seven of 17 patients (41%) with p53 overexpression versus 20 of 26 (77%) in whom p53 was not overexpressed (P = .007). CONCLUSION: p53 nuclear overexpression has independent prognostic value for survival in patients with invasive bladder cancer treated with neoadjuvant chemotherapy.

Changing pattern of expression of the epidermal growth factor receptor and transforming growth factor alpha in the progression of prostatic neoplasms.

The autocrine/paracrine interaction of the epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) has been implicated in prostate cancer cell growth and proliferation. To evaluate the role of EGFr and TGF-alpha in prostate cancer progression, we studied the immunohistochemical staining pattern of EGFr and TGF-alpha in malignant primary and hormone-independent metastatic prostate lesions. The specimens evaluated included 37 primary carcinomas (34 hormone-naive and 3 hormone-refractory tumors) and 22 metastases. For each specimen, the pattern of expression was evaluated and staining reactivities graded from 0-3, with 0 representing no staining and 3 representing homogeneous and intense staining. Primary malignant prostate epithelial cells in areas with discrete gland formation showed strong EGFr immunostaining, while stromal cells were generally nonreactive. In untreated primary tumors, TGF-alpha expression was primarily in the stroma, while epithelial cells were weakly positive in several cases. Malignant epithelial cells adjacent to neural elements that stained positive for TGF-alpha was frequently observed. A homogeneous staining pattern for EGFr was noted in 17 (89%) of 19 evaluable androgen-independent-refractory metastases, while TGF-alpha expression was found in 14 (78%) of 18 evaluable cases. Overall, 14 of 18 androgen-independent metastases coexpressed the receptor and the ligand. These results suggest that, unlike primary prostate tumors where a paracrine relationship between EGFr and TGF-alpha appears to predominate, the potential for autocrine stimulation may exist in the majority of metastatic androgen-independent tumors. Furthermore, the changing pattern of expression as the disease evolves from the localized hormone-naive to metastatic androgen-independent condition suggests that strategies aimed at blocking this growth factor pathway may be of therapeutic importance for androgen-independent disease.

[Prevention and treatment of atrial fibrillation after cardiac surgery]. / Prevention et traitement de la fibrillation atriale après chirurgie cardiaque.

The incidence of postoperative atrial fibrillation in cardiac surgery is still high despite major advances in anesthetic, pharmacological and surgical techniques. Its precise mechanism is still totally unknown. Postoperative atrial fibrillation increases length of stay as well as hospital costs. Rate of postoperative atrial fibrillation spontaneous conversion is high. Several protocols have been developed for prevention and/or treatment of postoperative atrial fibrillation. Beta-blockers, amiodarone and atrial pacing reduce.atrial fibrillation incidence as compared to placebo. On the other hand, amiodarone and propafenone achieve a high conversion rate of installed postoperative atrial fibrillation. However, among many pharmacological options, the best treatment is still to be defined.

[Three-dimensional renal angiography]. / Angiographie rénale tridimensionnelle.

The usefulness of three-dimensional angiography is not fully established except for neurovascular diseases. We report a case of significant renal artery stenosis not shown on conventional angiography because of its orientation along the axial plane, where 3D imaging allowed complete analysis of the lesion leading to endovascular treatment.

Role of cytochrome P450 metabolites of arachidonic acid in hypertension.

Considerable evidence has accumulated over the last decade implicating a role of cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA) in the pathogenesis of hypertension. Indeed, 20-hydroxyeicosatetraenoic acid (20-HETE) is produced by vascular smooth muscle (VSM) cells and is a potent vasoconstrictor that depolarizes VSM by blocking large conductance Ca+-activated K2+ channels. In contrast, epoxyeicosatrienoic acids (EETs) are synthesized by the vascular endothelium and have opposite effects on VSM (hyperpolarization and vasodilatation). Inhibition of the synthesis of 20-HETE attenuates myogenic tone and autoregulation of blood flow and modulates vascular responses to vasodilators (NO and CO) and vasoconstrictors (angiotensin II, endothelin). In the kidney, 20-HETE inhibits sodium transport in the proximal tubule by blocking Na+-K+-ATPase activity. In the thick ascending limb of the loop of Henle, 20-HETE inhibits Na+-K+-2Cl- transport, in part, by blocking a 70 pS apical K+ channel. EETs are produced in the proximal tubule where they inhibit Na+-H+ exchange and in the collecting duct where they inhibit sodium and water transport. Numerous studies have established that the formation of EETs and 20-HETE and the expression of CYP enzymes are altered in the kidney in many genetic and experimental animal models of hypertension and in some forms of human hypertension. However, the functional significance of these changes remains to be determined. Given the importance of this pathway in the control of renal function and vascular tone, it is likely that alterations in the renal formation of CYP-dependent metabolites of AA will be shown to participate in the development of hypertension in many of these models.

Bladder cancer: advances in biology and treatment.

Integrating systemic chemotherapy in the treatment of patients with invasive bladder cancer is essential to improve survival because the majority of deaths are from systemic relapse. However, as experience with invasive tumors evolves, it is clear that treatment recommendations need to be tailored to an individual patient based on metastatic risk and, ideally, sensitivity to treatment. For those with tumors that do not extend through the bladder wall, standard therapy remains radical surgery. Nevertheless, encouraging results are being reported with increasing frequency using strategies designed to preserve bladder function through a variety of means. Crucial to the recommendation of a specific approach for an individual is improving our ability to define prognosis prior to initiating treatment. Patients with a high risk of systemic recurrence generally require chemotherapy, although the optimal route of integration, pre vs. post-operatively, remains controversial. In those patients who require it, chemotherapy can be administered more safely with the concomitant administration of hematopoietic growth factors. These factors alone, however, are unlikely to improve overall survival. Crucial to the latter effort will be the identification of more active agents, improving our understanding of intrinsic and acquired resistance to chemotherapy, and better delivery of the chemotherapeutic agents currently available. Of equal importance, is the enrollment of patients in clinical trials. These can include large scale randomized comparisons with using a survival end-point, as well as new therapies in high risk populations. The latter would include patients with advanced T3b, T4 and N+ disease, with a high risk of metastatic failure, and low complete response proportions to presently available regimens.

Tobacco smoking, occupation, and p53 nuclear overexpression in early stage bladder cancer.

Epidemiological studies show an increased risk of bladder cancer associated with tobacco smoking and occupational exposures. Certain carcinogens in tobacco and occupational exposures cause DNA damage and may produce specific mutations. TP53 is considered a common target for carcinogenic agents, and mutations of this gene are reported to be the most frequent nuclear abnormalities in human cancer. In order to investigate the relationship between tobacco smoking, occupations, and altered patterns of p53 expression, we have analyzed a group of 109 incident patients with superficial transitional cell carcinoma of the bladder. We assessed p53 nuclear overexpression by the use of anti-p53 antibody PAb1801 and immunohistochemistry, and identified 45 of 109 patients (41%) displaying p53-positive phenotype. We observed a significant association between the number of cigarettes smoked per day and p53 nuclear overexpression (p = 0.02). The odds ratios were 2.3 for those smoking 1-2 packs per day and 8.4 for smoking more than 2 packs per day. Similar estimates were obtained after controlling for age, sex, and race. Elevated odds ratios were also observed for dye-/ink-related (odds ratio = 2.0; 95% CI, 0.4-9.4) and cooking-related occupations (1.8, 0.6-5.0), although those were not statistically significant. These data support the hypothesis that certain carcinogens derived from cigarette smoking and occupations may induce TP53 mutations, which in turn are involved in early steps of bladder carcinogenesis.

Factors associated with p53 nuclear accumulation in prostatic adenocarcinoma.

Prostatic adenocarcinoma is an age-related cancer. The extremely high proportion of this disease with advanced age merits the study of age-dependent carcinogenesis. TP53 is considered a common target for carcinogenic agents including exogenous carcinogens as well as endogenous mutagens. Mutations of this gene are reported to be the most frequent nuclear abnormalities in human cancer. In order to investigate the relationship between age and altered patterns of p53 expression, we have analyzed a group of 48 patients with primary prostatic adenocarcinoma. We assessed p53 nuclear accumulation immunohistochemically by the anti-p53 antibodies PAb1801 and CM-1, and identified 9 out of 48 patients (19%) displaying p53-positive phenotype. We observed a significant association between advanced age and p53 nuclear accumulation. The data suggest that p53 nuclear accumulation may be related to the aging process in prostatic adenocarcinoma.