Oral Condition and Incident Coronary Heart Disease: A Clustering Analysis.

Poor oral health has been linked to coronary heart disease (CHD). Clustering clinical oral conditions routinely recorded in adults may identify their CHD risk profile. Participants from the Paris Prospective Study 3 received, between 2008 and 2012, a baseline routine full-mouth clinical examination and an extensive physical examination and were thereafter followed up every 2 y until September 2020. Three axes defined oral health conditions: 1) healthy, missing, filled, and decayed teeth; 2) masticatory capacity denoted by functional masticatory units; and 3) gingival inflammation and dental plaque. Hierarchical cluster analysis was performed with multivariate Cox proportional hazards regression models and adjusted for age, sex, smoking, body mass index, education, deprivation (EPICES score; Evaluation of Deprivation and Inequalities in Health Examination Centres), hypertension, type 2 diabetes, LDL and HDL serum cholesterol (low- and high-density lipoprotein), triglycerides, lipid-lowering medications, NT-proBNP and IL-6 serum level. A sample of 5,294 participants (age, 50 to 75 y; 37.10% women) were included in the study. Cluster analysis identified 3,688 (69.66%) participants with optimal oral health and preserved masticatory capacity (cluster 1), 1,356 (25.61%) with moderate oral health and moderately impaired masticatory capacity (cluster 2), and 250 (4.72%) with poor oral health and severely impaired masticatory capacity (cluster 3). After a median follow-up of 8.32 y (interquartile range, 8.00 to 10.05), 128 nonfatal incident CHD events occurred. As compared with cluster 1, the risk of CHD progressively increased from cluster 2 (hazard ratio, 1.45; 95% CI, 0.98 to 2.15) to cluster 3 (hazard ratio, 2.47; 95% CI, 1.34 to 4.57; P < 0.05 for trend). To conclude, middle-aged individuals with poor oral health and severely impaired masticatory capacity have more than twice the risk of incident CHD than those with optimal oral health and preserved masticatory capacity (ClinicalTrials.gov NCT00741728).

Arthroscopic subtalar arthrodesis.

Arthroscopic subtalar arthrodesis is gaining in popularity based on evidence of bone fusion in over 90% of cases, with a shorter time to healing, a simpler postoperative course, and fewer complication compared to open surgery. Two arthroscopic techniques have been reported: one with the patient in lateral decubitus and lateral portals and the other with the patient prone and posterior portals. The objective of this technical note is to describe these two techniques, with emphasis on the specific characteristics of each.

Outcome of aggressive fibromatosis treated with radiation therapy.

INTRODUCTION: The purpose of this study is to report the clinical course and outcome in 7 patients with aggressive fibromatosis. MATERIAL AND METHODS: Between the years 2000 and 2003, 7 patients who were treated with combined modalities were evaluated retrospectively. Patients' demographic information, including age and gender, tumour characteristics, surgical resection, and the use of radiotherapy were recorded and evaluated. RESULTS: The mean patient age was 34 years. The median time to follow-up was 15.5 months. Resection was performed with positive surgical margins in three cases. Three patients were evaluated as inoperable and one patient was treated with debulking surgery. All patients received radiation therapy with a median dose of 51 Gy. At follow-up, three patients had no evidence of disease, three patients were alive with disease, and one patient died 15 days after radiotherapy. CONCLUSION: Local control is the primary problem in aggressive fibromatosis. There is no appropriate treatment for aggressive fibromatosis and the type of treatment depends on tumour characteristics and location as well as patient characteristics.

Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine

We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB) or abdominopelvic (AP) irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g) in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset) or evening (activity span - 13 h after light onset). Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively) to the irradiated rats. AP (P < 0.05) and TB (P < 0.05) irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS) levels. Melatonin treatment in the morning (P < 0.05) or evening (P < 0.05) decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05). Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine.

We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB) or abdominopelvic (AP) irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g) in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset) or evening (activity span - 13 h after light onset). Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively) to the irradiated rats. AP (P < 0.05) and TB (P < 0.05) irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS) levels. Melatonin treatment in the morning (P < 0.05) or evening (P < 0.05) decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05). Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

The European Organization for Research and Treatment of Cancer core quality of life questionnaire (QLQ-C30 version 3.0 Turkish) in cancer patients receiving palliative radiotherapy.

The aim of this study was to evaluate the efficacy of palliative radiotherapy in patients with advanced cancer in terms of improvement in the quality of life [quality of life questionnaire (QLQ)], and to assess the correlation between the Eastern Cooperative Oncology Group (ECOG) performance status and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (Turkish version 3.0). A total of 88 patients with advanced malignant disease treated with palliative radiotherapy were included in the study. All patients completed the EORTC QLQ-C30 questionnaire before and after treatment, and the patient performance status during the pre-treatment and post-treatment phase (ECOG 2) was correlated to the EORTC QLQ C-30 with subscales. Most patients (87.5%) had metastatic disease, and the remaining (12.5%) had locally advanced disease. Comparing the patients in terms of performance status, those with a better performance status (

Interferon gamma-secreting HCV-specific CD8+ T cells in the liver of patients with chronic C hepatitis: relation to liver fibrosis--ANRS HC EP07 study.

Little is known about the role of specific hepatitis C virus (HCV) CD8+ T cells in liver damage, especially for the progression of fibrosis, during the highly variable course of chronic C hepatitis. The aim of this study was to investigate the presence of HCV-specific CD8+ T cells in the liver of patients with chronic C hepatitis and to examine their clinical significance by relating the response to liver fibrosis and progression rate, serum viral load, serum aminotransferase levels, inflammatory activity and in situ characteristics of the intrahepatic infiltrate. Fifteen patients were prospectively included in the study. Intrahepatic lymphocytes were tested for interferon gamma (IFNg) production in response to HCV class I-restricted epitopic peptides using enzyme-linked immunospot analysis. Liver biopsy samples were evaluated for fibrosis, fibrosis progression rate, activity, and in situ number of CD8+ cytotoxic lymphocytes and apoptotic cells. An IFNg-specific CD8+ T-cell response was detected in the liver samples of 47% of patients which was significantly related to a lower stage of fibrosis (P = 0.02) and a lower progression rate of fibrosis (P = 0.01). It was neither related to the number of cytotoxic lymphocytes infiltrating the liver nor to hepatocyte apoptosis. In conclusion, our results indicate that the presence of HCV-specific IFNg-secreting T cells in the liver of patients with chronic C hepatitis is associated with low liver fibrosis and fibrosis progression rate, suggesting that these IFNg-secreting T cells might limit the progression of liver damage.

Determination of optimum planning target volume margins for various tumor sites using electronic portal imaging.

OBJECTIVE: The aim of this study is to evaluate the efficacy of electronic portal imaging (EPI) to measure the set-up errors for four different sites of irradiation caused by patient positioning. METHODS: A total number of 95 portal images of 11 patients (3 pelvic, 1 total cranium, 3 mantle and 4 tangential fields for breast) were collected during the course of study. The first portal images after a correction of set-up errors according to the simulation films were accepted as the reference images for the subsequent sessions. By matching each portal image with the reference image, the deviations in lateral (x) and superior-inferior (y) axis for all and additionally in antero-posterior (z) axis for pelvis, and standard deviations were calculated. RESULTS: The set-up errors caused by patient's positioning are completely abolished in 15 mm planning target volume (PTV) margins for all studied cases. CONCLUSION: Standard PTV margins usually completely cover the set-up errors caused by patient's positioning.

Three-dimensional conformal breast irradiation in the prone position

The prone position can be used for the planning of adjuvant radiotherapy after conservative breast surgery in order to deliver less irradiation to lung and cardiac tissue. In the present study, we compared the results of three-dimensional conformal radiotherapy planning for five patients irradiated in the supine and prone position. Tumor stage was T1N0M0 in four patients and T1N1M0 in one. All patients had been previously submitted to conservative breast surgery. Breast size was large in three patients and moderate in the other two. Irradiation in the prone position was performed using an immobilization foam pad with a hole cut into it to accommodate the breast so that it would hang down away from the chest wall. Dose-volume histograms showed that mean irradiation doses reaching the ipsilateral lung were 8.3 ± 3.6 Gy with the patient in the supine position and 1.4 ± 1.0 Gy with the patient in the prone position (P = 0.043). The values for the contralateral lung were 1.3 ± 0.7 and 0.3 ± 0.1 Gy (P = 0.043) and the values for cardiac tissue were 4.6 ± 1.6 and 3.0 ± 1.7 Gy (P = 0.079), respectively. Thus, the dose-volume histograms demonstrated that lung tissue irradiation was significantly lower with the patient in the prone position than in the supine position. Large-breasted women appeared to benefit most from irradiation in the prone position. Prone position breast irradiation appears to be a simple and effective alternative to the conventional supine position for patients with large breasts, since they are subjected to lower pulmonary doses which may cause less pulmonary side effects in the future

Three-dimensional conformal breast irradiation in the prone position.

The prone position can be used for the planning of adjuvant radiotherapy after conservative breast surgery in order to deliver less irradiation to lung and cardiac tissue. In the present study, we compared the results of three-dimensional conformal radiotherapy planning for five patients irradiated in the supine and prone position. Tumor stage was T1N0M0 in four patients and T1N1M0 in one. All patients had been previously submitted to conservative breast surgery. Breast size was large in three patients and moderate in the other two. Irradiation in the prone position was performed using an immobilization foam pad with a hole cut into it to accommodate the breast so that it would hang down away from the chest wall. Dose-volume histograms showed that mean irradiation doses reaching the ipsilateral lung were 8.3+/-3.6 Gy with the patient in the supine position and 1.4+/-1.0 Gy with the patient in the prone position (P = 0.043). The values for the contralateral lung were 1.3+/-0.7 and 0.3+/-0.1 Gy (P = 0.043) and the values for cardiac tissue were 4.6+/-1.6 and 3.0+/-1.7 Gy (P = 0.079), respectively. Thus, the dose-volume histograms demonstrated that lung tissue irradiation was significantly lower with the patient in the prone position than in the supine position. Large-breasted women appeared to benefit most from irradiation in the prone position. Prone position breast irradiation appears to be a simple and effective alternative to the conventional supine position for patients with large breasts, since they are subjected to lower pulmonary doses which may cause less pulmonary side effects in the future.

Early results of exclusive radiotherapy in advanced stage cervical carcinoma performed with reference to ICRU Report 38.

BACKGROUND AND PURPOSE: Most of the studies in which medium dose rate (MDR) or high dose rate (HDR) brachytherapy have been used for the treatment of cervical carcinoma were prescribed according to the Manchester system. This study aims to present early results of exclusive radiotherapy, which includes MDR brachytherapy, performed using ICRU 38 recommendations to their full extent. MATERIALS AND METHODS: Between 1994 and 1997, 80 patients with advanced stage (FIGO stages IIA-IVA) cervical carcinoma received external beam therapy (EBT) to the pelvis at a total dose of 46 to 50 Gy and two fractions of MDR (approximately 11.5 Gy/h) brachytherapy delivered to the 60 Gy reference isodose. A dose correction factor of 0.80 was used for dose rate effect. Additionally, 10-14 Gy EBT was given as a parametrial boost. Mean follow-up duration was 25.7 months. RESULTS: Local control (LC) and 3-year overall survival were 63% and 68%, respectively, for all patients. For stages II, III, and IV, LC was 75%, 44%, and 60% and 3-year survival was 75%, 62%, and 50%, respectively. Seven patients had severe late complications (8.7%). CONCLUSIONS: The results of this study encourage the use of ICRU 38 recommendations with MDR or HDR brachytherapy with some additional measures in terms of the radiobiological aspect.

Lipopeptide presentation pathway in dendritic cells.

Lipopeptides are currently being evaluated as candidate vaccines in human volunteers. They elicit cytotoxic responses from CD8(+) T lymphocytes, whereas peptides without a lipidic moiety usually do not. The exact processing and presentation pathways leading to association with MHC class I molecules has not yet been defined. This is of particular interest in dendritic cells, which are required for primary T cell stimulation. We have tracked lipopeptides derived from an HLA-A2.1-restricted HIV-1 Reverse Transcriptase epitope, by N-terminal addition of an N-epsilon-palmitoyl-lysine. Entry of the lipopeptides into human monocyte-derived dendritic cells (MDC) was mediated by endocytosis, as assessed by colocalization using analogs labelled with rhodamine, and by confocal microscopy. This internalization in DC induced functional stimulation of CD8(+) T lymphocytes specific for the epitopes, quantified by Interferon-gamma ELISPOT assays. The peptide alone was not visualized inside the DC and was only presented through direct surface association to HLA-A*0201. Therefore, lipopeptides provide a model system to define precisely the cross-presentation pathways that lead exogenous proteins to associate with class I MHC molecules within dendritic cells. Using this approach, cross-presentation pathways can be better defined and vaccine lipopeptides can be further optimized for MHC class I association in human dendritic cells.

Downregulation of major histocompatibility class I on human dendritic cells by HIV Nef impairs antigen presentation to HIV-specific CD8+ T lymphocytes.

The HIV early regulatory Nef protein downregulates surface expression of major histocompatibility class I (MHC I) molecules on various immortalized cell lines and on T lymphocytes. MHC I-restricted presentation induces CD8+ T cell responses, which have a major role in limiting HIV infection. Induction of primary immune responses requires dendritic cells, which are major candidates as the first cells that can internalize the virus and present it to T cells in mucosal contamination. To test the effect of Nef on MHC I-restricted antigen presentation by dendritic cells, we used recombinant vaccinia viruses. Flow cytometric analysis of double labeling for a vaccinia protein and MHC I showed that HIV-1 Lai Nef indeed downregulated MHC I surface expression on dendritic cells. MHC I-restricted presentation to a Nef-specific CD8+ cell clone from an infected patient was decreased in an interferon gamma ELISpot assay. Presentation of a reverse transcriptase epitopic peptide on sorted Nef-infected cells was decreased in a peptide concentration-dependent way, confirming the role of MHC I downregulation in the impairment of the CD8+ cell-specific response. Therefore, Nef downregulates MHC I surface expression on human dendritic cells, impairing presentation to HIV-specific CD8+ cells. This action of Nef probably induces a deleterious delay in the early CD8+ responses during the first days of infection and at the onset of new viral mutants.

Paratracheal extramedullary hematopoiesis.

Extramedullary hematopoiesis (EMH) is a rare finding in hematology. A 73-year-old female patient with a 1-week history of severe progressive dyspnea was examined, and computed tomography (CT) showed a paratracheal mass 3 cm in size located 1 cm below the vocals cords and causing obliteration of the tracheal airway. Cytology of a needle biopsy revealed EMH. External radiotherapy of 200-cGy fractions to a total dose of 2000 cGy was administered with 3-dimensional conformal planning to treat the progressive symptoms. The patient's clinical symptoms started to improve 2 days after radiotherapy and had completely disappeared after 7 days. CT scans showed complete response on follow-up at 1 week to 5 months after radiotherapy. Mature and immature hematopoietic cells and many adipose cells were seen in the pretreatment samples. Histologic findings in the posttreatment samples showed that these cells had completely disappeared due to the conformal radiotherapy. On the basis of clinical, radiologic, and histologic results, we suggest that conformal radiotherapy may be useful for the treatment of paratracheal localization of EMH because good tumoral irradiation was obtained in this case, with the protection of normal tissues.

Conformal radiotherapy in primary non-Hodgkin's lymphoma of the male urethra.

Primary malignant lymphoma of the urethra is very rare. Fifteen cases are reported in the literature and only four of them belong to the male urethra. We present the fifth case of primary Non-Hodgkin's lymphoma of the male urethra that is managed by conformal radiotherapy.

Direct evidence to support the role of antigen-specific CD8(+) T cells in melanoma-associated vitiligo.

Vitiligo is a cutaneous pigmentary disorder characterized by the loss of melanocytes. An autoimmune mechanism is strongly suspected to be involved in this affection given that it is frequently associated with autoimmune hormonal disorders, and because antibodies directed against melanocytic antigens are found in the serum of patients with vitiligo. We examined the role of cellular immunity in melanoma-associated vitiligo by expanding infiltrating lymphocytes from fresh biopsy specimens of vitiligo patches in melanoma patients. The vitiligo-infiltrating lymphocytes were almost exclusively T lymphocytes, and most were CD8(+). Following in vitro expansion, vitiligo-infiltrating lymphocytes remained predominantly CD8(+) and expressed the cutaneous homing receptor CLA. Furthermore, vitiligo-infiltrating lymphocytes had a clonal or oligoclonal T cell receptor profile, possibly reflecting specific antigenic stimulation. Finally, vitiligo- infiltrating lymphocytes specifically recognized differentiation antigens shared by normal melanocytes and melanoma cells. This direct demonstration of CD8(+) T cell involvement in vitiligo suggests that, in melanoma patients, vitiligo may be a visible effect of a spontaneous antitumoral immune response.

Endocytosis of an HIV-derived lipopeptide into human dendritic cells followed by class I-restricted CD8(+) T lymphocyte activation.

CD8(+) T lymphocytes, which are major immune effectors, require primary stimulation by dendritic cells (DC) presenting MHC class I molecule-bound epitopes. Sensitization to exogenous protein epitopes that are not synthesized in DC, such as cross-priming, is obtained through pathways leading to their association with MHC class I. To follow class I-restricted pathways in human DC, we have tracked a lipopeptide derived from the conserved HLA-A*0201-restricted HIV-1 reverse transcriptase 476-484 epitope, by N-terminal addition of an Nepsilon-palmytoyl-lysine. Indeed, lipopeptides elicit cytotoxic responses from CD8(+) T lymphocytes, whereas peptides without a lipid moiety do not. The lipopeptide and its parent peptide were labeled unequivocally by rhodamine to study their entry into immature monocyte-derived human DC by confocal microscopy. The lipid moiety induced endocytosis of the lipopeptide, assessed by rapid entry into vesicles, colocalization with Dextran-FITC and dependence on energy. Internalization occurred even when actin filaments were depolymerized by Cytochalasin B. This internalization induced functional stimulation of specific CD8(+) T lymphocytes in IFN-gamma ELISPOT assays. The peptide alone was not visualized inside the DC and was presented through direct surface association to HLA-A*0201. Therefore, lipopeptides are a unique opportunity to define precisely the pathways that lead exogenous proteins to associate with MHC class I molecules in DC. The results will also be useful to design lipopeptide vaccines.

Ten-year clinical and angiographic follow-up of coronary wallstent.

Although stents have been implanted in human coronary arteries since 1986, the long-term angiographic outcome of coronary stenting is unknown. We performed 10-year angiographic follow-up in 8 patients who had undergone stent implantation without acute complications or 6-months' restenosis. Analysis of the changes in minimal luminal diameter within the stent and the reference vessel diameter of the stented segment at 10 years do not suggest that atherosclerosis is accelerated or prolonged beyond 6 months within coronary stents.

Extension of HLA-A*0201-restricted minimal epitope by N epsilon-palmitoyl-lysine increases the life span of functional presentation to cytotoxic T cells.

The delineation of the minimal requirements for efficient delivery of functional cytotoxic epitopes into APC could be a step toward the definition of "minimal length" lipopeptides for the modulation of CTL activity. Several analogues of the HLA-A*0201-restricted HIV-1 polymerase (pol476-484) minimal cytotoxic epitope were obtained by modifying P0, P1, or P10 positions by a single N epsilon-palmitoyl-lysine residue. The use of fluorescent derivatives confirmed the cell-permeating activities and suggested that a P0- and a P1-modified lipopeptide possessing ionizable extremities fulfills the structural requirements for MHC loading. The expressions of HLA-peptide complexes at the surface of TAP-deficient cells incubated with the parent epitope or lipopeptide derivatives were compared, in terms of intensity and stability. Both lipopeptides induced a considerably prolonged expression of conformationally correct complexes, which were dependent on the integrity of the exocytosis pathway, suggesting a dynamic mechanism of formation or reloading of the complexes from an intracellular pool. The agonistic activities of the different HLA-peptide complexes were evaluated using two independent T cell lines from HIV-infected donors. We report that a lipodecapeptide obtained by N-terminal addition of a N epsilon-palmitoyl-lysine to the pol476-484 epitope was able to increase the life span of functional presentation to cytotoxic T cells specific for the parent peptide.