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Objective: The aim of the study was to assess the effect of non-surgical periodontal therapy (NSPT) on periodontal and cardiac parameters as well as on the expression of calprotectin and periostin levels in periodontitis patients with and without coronary artery disease (CAD)., Methods: Ninety subjects were categorised into three groups: Group H: periodontally and systemically healthy subjects, Group P: stage III grade B periodontitis subjects with no associated systemic diseases and Group P + CAD: stage III grade B periodontitis subjects diagnosed with CAD. Demographic, periodontal and cardiac parameters were recorded at baseline (0 day) and on the 180th day after NSPT. Gingival crevicular fluid was collected from all participants at baseline (0 day) and after the 180th day. Calprotectin and periostin expression were reassessed., Results: A significant increase in the levels of calprotectin (34.05 ± 11.72) was seen at baseline in the P + CAD group, whereas on the contrary, a decreased periostin (1.59 ± 0.41) was also noted at baseline. The study also showed a significant improvement in periodontal and cardiac parameters on the 180th day following NSPT., Conclusion: Detection of calprotectin and periostin expression in GCF samples could represent a link to the association of periodontitis and CAD., (© 2023 Wiley Periodicals LLC.)

Background: Although there is ample evidence in the literature supporting a significant positive association between key periodontal pathogens and established inflammatory markers of periodontitis and coronary artery disease (CAD), their exact role remain unclear. Especially, the role of viruses in the etiology and specific biomarkers have not been validated. Thus, the current study aims to evaluate the role of periodontal viruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV), as well as the inflammatory marker pentraxin-3 (PTX3), and to analyze their association with CAD., Methods: The study included 240 patients divided into four groups of 60 patients each: nonperiodontitis + noncardiac (NP+NC) group, periodontitis + noncardiac patients (P+NC) group, nonperiodontitis + cardiac patients (NP+C) group, and periodontitis + cardiac (P+C) group. The cardiac surgery group (C-S) was a subgroup of NP+C and P+C. It consisted of 60 patients from the abovementioned two cardiac groups in whom coronary artery bypass graft (CABG) was indicated. Demographic variables, cardiac parameters, and periodontal parameters were recorded. The viruses (EBV, CMV, and HSV) and the inflammatory marker PTX3 were evaluated in the subgingival plaque samples of all the four groups and atheromatous plaque samples of the C-S using reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative polymerase chain reaction (qPCR), respectively, and were compared between the groups. The results were obtained and statistically analyzed., Results: The demographic variables did not differ significantly between the groups, except for age. Systolic blood pressure, diastolic blood pressure, low-density lipoprotein, and random blood sugar were significantly higher in NP+C and P+C, whereas high-density lipoprotein was significantly lower (p ≤ 0.05) in the same. Plaque index (PI), probing pocket depth (PPD), and clinical attachment level (CAL) were significantly higher (p ≤ 0.05) in P+NC and P+C. PTX were significantly elevated in P+C among the four groups. On evaluating the subgingival plaque samples, EBV and CMV were significantly higher in the two periodontitis groups P+NC and P+C (p = 0.000). HSV was significantly higher in the two cardiac groups (NP+C and P+C) (p ≤ 0.05). Cardiac EBV and CMV were significantly elevated in the P+C group with a p value of 0.004 and 0.033, respectively. Cardiac HSV was found in the NP+C group with statistical insignificance (p = 0.410) between the groups. On correlation, oral PTX were significantly associated with bleeding index (BI), PPD, and CAL (p = 0.000). Similarly, cardiac PTX showed significant association with PI, BI, PPD, and CAL (p = 0.000). Oral and cardiac PTX also showed significant correlation with each other. Multiple logistic regression analysis revealed a significant association between CAL and oral EBV (p ≤ 0.05). Similarly, cardiac EBV showed a significant association with CAL and oral EBV (p ≤ 0.05). Multiple logistic regression analysis also revealed that both cardiac and oral PTX showed a significant association only with oral EBV, CMV, and HSV., Conclusion: The results of the current study suggest that the clinical severity of periodontitis (CAL), etiology of periodontitis (EBV and CMV), and inflammatory marker of periodontitis (PTX3) were found to be significantly elevated in CAD. These findings suggests that periodontal diseases may be a risk factor that could influence the progression of CAD., (© 2023 American Academy of Periodontology.)

Introduction: According to the Institute for Safe Medication Practices, unfractionated heparin is a high-risk medication due to the potential for medication errors and adverse events. Unfractionated heparin is often started in the emergency department for patients with acute coronary syndromes or coagulopathies. Risk-mitigation strategies should be implemented to ensure appropriate initiation and monitoring of this high-risk medication. In 2019, an unfractionated heparin calculator was built into the electronic health record at a community medical center. The purpose of this study was to evaluate the impact of the calculator as a risk-mitigation strategy., Methods: Patients ≥18 years old admitted between January 1, 2020, and December 31, 2020, were included if they were administered an unfractionated heparin infusion in the emergency department. Patient encounters were excluded if unfractionated heparin order was discontinued before administration. Patient encounters were classified into the unfractionated heparin calculator arm if the unfractionated heparin calculator was used to determine initial dosing, and the remaining patient encounters were classified into the unfractionated heparin no calculator arm. Unfractionated heparin orders were reviewed if a baseline activated partial thromboplastin time was collected and if the correct initial bolus dose and infusion rate were administered. The primary objective is to determine whether the use of unfractionated heparin initiation calculator reduced the rate of medication administration errors. Medication administration errors are defined as baseline activated partial thromboplastin time not collected or incorrectly collected or the administration of incorrect initial bolus dose and infusion rate., Results: A total of 356 patient encounters with unfractionated heparin orders were included in the primary analysis. There were 13.9% errors (39 of 279) present when the calculator was used and 23.3% (18 of 77) when the calculator was not used (P = .046). There was 86% correct administration of heparin (240 of 279) when the calculator was used and 76% correct administrations (59 of 77) when the calculator was not used., Discussion: The use of the unfractionated heparin infusion calculator in the emergency department led to decrease in medication administration errors. This is the first study to evaluate the integration of an unfractionated heparin calculator into the electronic health record., (Copyright © 2023 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Objectives: Pentraxin 3 (PTX3) is a biomarker, associated with the pathogenesis of Periodontitis and coronary artery disease (CAD) individually, but their role in patients with both diseases remains unclear. The current study aims to evaluate the association of PTX in patients with concomitant periodontitis and CAD., Materials and Methods: In a case-control study, 240 participants were selected and divided into four groups. Nonperiodontitis + noncardiac = 60 patients, periodontitis + noncardiac (P + NC) = 60 patients, nonperiodontitis + cardiac (NP + C) = 60 patients, periodontitis + cardiac (P + C) = 60 patients. Demographic variables, cardiac and periodontal parameters were recorded. PTX was evaluated in the subgingival plaque and atheromatous plaque samples using real-time quantitative polymerase chain reaction and compared between the groups. The results were statistically analyzed., Results: Among the demographic variables, age showed a significant difference between the groups. Systolic and diastolic blood pressure, low-density lipoprotein, and random blood sugar were significantly higher in NP + C and P + C groups ( P ≤ 0.05). The plaque index, probing pocket depth, and clinical attachment loss were significantly higher in P + NC and P + C groups ( P ≤ 0.05). PTX was significantly elevated in P + C group ( P = 0.000). Pearson's correlation revealed a significant correlation between the periodontal parameters and PTX in both the cardiac and oral samples., Conclusion: PTX3 levels were elevated in CAD patients with periodontitis suggesting the influence of periodontal inflammation in the progression of CAD. PTX3 may serve as a diagnostic and prognostic tool for both periodontitis and CAD. This study could provide an understanding and awareness about the potential role of PTX3 in both periodontitis and CAD., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Society of Periodontology.)

Objectives: The current study aimed in evaluating the prevalence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV) in periodontitis and/or coronary artery disease (CAD) patients to compare with their healthy controls and insist their significance in the same., Methodology: Two hundred and forty patients were divided into 4 groups. Non-periodontitis+non-cardiac (NP+NC) = 60 patients, periodontitis+non-cardiac patients (P+NC) = 60 patients, non-periodontitis+cardiac patients (NP+C) = 60 patients, and periodontitis+cardiac (P+C) = 60 patients. Demographic variables, cardiac and periodontal parameters were recorded. EBV, CMV, and HSV were evaluated in the subgingival plaque samples using RT-PCR (real-time polymerase chain reaction) and compared between the groups. The results were statistically analyzed using Student's t-test, Pearson's chi-square, Turkey post hoc analysis, and multiple logistic regression analysis., Results: The demographic variables did not differ significantly between the groups, except for age. Systolic blood pressure, diastolic blood pressure, low-density lipoprotein, and random blood sugar were significantly higher in NP+C and P+C (p ≤ 0.05). The plaque index, probing pocket depth, and clinical attachment loss (p ≤ 0.05) were significantly higher in P+NC and P+C. EBV and CMV were significantly higher in the two periodontitis groups P+NC and P+C (p-value = 0.000). HSV was significantly higher in the two cardiac groups (NP+C and P+C) (p≤0.05). Multiple logistic regression analysis revealed a significant association between EBV and CAL (p ≤ 0.05)., Conclusion: The study concluded that higher prevalence of EBV and CMV was found in groups with periodontitis patients. This indicates the significant role of the viruses in periodontitis as confirmed by association between EBV and CAL. The viruses were said to be highest in periodontitis patients with CAD. This could pave a new link in the risk of CAD in periodontitis patients., (© 2022 Wiley Periodicals LLC.)

Background: The current study aims to determine the expression of trefoil factor 2 (TFF2), trefoil factor 3 (TFF3), and adrenomedullin (ADM) in salivary samples of periodontitis patients with and without coronary heart disease (CHD)., Methods: A total of 75 patients were selected based on the inclusion and exclusion criteria and divided into three groups of 25 patients each: generalized periodontitis (GP) only; GP+CHD; and CHD only. Demographic, periodontal, and cardiac parameters were recorded, and unstimulated saliva samples were collected and analyzed for the expression of TFF2, TFF3, and ADM., Results: Among the demographic variables, the means for age, weight, and body mass index were significantly different between the groups on statistical analysis. Plaque index, bleeding on probing, probing pocket depth, clinical attachment level, and the expression of TFF2 were highest in the GP+CHD group, and ADM was highest in the CHD group, with P values of < 0.01 as compared to the other groups. TFF2, TFF3, and ADM were also correlated with the demographic and periodontal parameters., Conclusions: The study demonstrates significantly elevated levels of TFF2 in CHD and GP patients, and a higher expression of ADM in CHD patients only, suggesting the possibility of an underlying inflammatory mechanism., (© 2022 American Academy of Periodontology.)

Background: and Purpose: The aim of this study was to assess, compare and correlate the ability of PCSK9 and IL6 as potential common serum and salivary biomarkers for stage III/IV periodontitis and the risk of developing atherosclerotic cardiovascular diseases., Methods: 76 patients were alloted into 4 groups consisting of subjects with clinically healthy periodontium and stage III/IV periodontitis with and without ACVD. Clinical parameters - PD, CAL, number of teeth, PI, mSBI, TC, Tg, HDL and LDL were recorded. Serum and saliva samples were obtained and subjected to ELISA for quantifying the biomarker levels., Results: The level of these biomarkers was found to be the lowest (IL6 Serum: 21.92 ± 14.54, IL6 Saliva: 12.34 ± 7.72, PCSK9 Serum: 178.82 ± 35.07, PCSK9 Saliva: 80.82 ± 25.43) in group I and highest in group IV (IL6 Serum: 73.4 ± 24.86, IL6 Saliva: 37.66 ± 15.77, PCSK9 Serum: 346.54 ± 45.11, PCSK9 Saliva: 157.72 ± 43.28). The clinical parameters PI, mSBI, PPD, CAL, total number of teeth, TC, HDL and LDL showed a significant correlation with biomarkers PCSK9 and IL6., Conclusion: This study features the elevation of serum and salivary PCSK9 and IL6 in periodontitis and ACVD. A triad of serum and salivary PCSK9 and IL6 along with the clinical markers of periodontal disease can relatively predict the future risk of developing ACVD., (© 2022 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)

The Severe Acute Respiratory Syndrome (SARS)-CoV-2 virus caused COVID-19 pandemic has led to various kinds of anxiety and stress in different strata and sections of the society. The aim of this study is to analyse the sleeping and anxiety disorder for a wide distribution of people of different ages and from different strata of life. The study also seeks to investigate the different symptoms and grievances that people suffer from in connection with their sleep patterns and predict the possible relationships and factors in association with outcomes related to COVID-19 pandemic induced stress and issues. A total of 740 participants (51.3% male and 48.7% female) structured with 2 sections, first with general demographic information and second with more targeted questions for each demographic were surveyed. Pittsburgh Sleep Quality Index (PSQI) and General Anxiety Disorder assessment (GAD-7) standard scales were utilized to measure the stress, sleep disorders and anxiety. Experimental results showed positive correlation between PSQI and GAD-7 scores for the participants. After adjusting for age and gender, occupation does not have an effect on sleep quality (PSQI), but it does have an effect on anxiety (GAD-7). Student community in spite of less susceptible to COVID-19 infection found to be highly prone to psychopathy mental health disturbances during the COVID-19 pandemic. The study also highlights the connectivity between lower social status and mental health issues. Random Forest model for college students indicates clearly the stress induced factors as anxiety score, worry about inability to understand concepts taught online, involvement of parents, college hours, worrying about other work load and deadlines for the young students studying in Universities., Competing Interests: Conflicts of interest/Competing interestsThe authors declare no conflict of interest., (© The Author(s) under exclusive licence to International Union for Physical and Engineering Sciences in Medicine (IUPESM) 2022.)

Background: Viruses are considered to be a newer family associated with inflammatory diseases. Yet the role of periodontal viruses in coronary artery diseases (CAD) remains unclear. Thus, the current study aims to evaluate the prevalence of periodontal viruses and compare the same in cardiac samples of CAD patients with and without periodontitis., Methods: A total of 60 patients with CAD indicated for coronary artery bypass graft surgery (CABG) were included. These were grouped into 36 patients with healthy periodontium (CAD only) and 24 patients with periodontitis (CAD + P). The demographic variables, cardiac parameters and periodontal parameters were recorded. Cardiac tissue samples were collected during the CABG surgery and were analyzed by reverse transcriptase polymerase chain reaction for periodontal viruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and Herpes simplex virus. All the parameters were statistically analyzed., Results: Among the demographic variables, age was statistically significant between the groups. Plaque index, bleeding index, probing depth, and clinical attachment level (CAL) were significantly higher in CAD+P group (P ˂0.05). Periodontal viruses such as EBV and CMV were significantly higher (62.5% and 75% respectively, P ˂0.05) in the cardiac samples of the CAD+P than CAD only (25% and 47.2%, respectively). A significant association between EBV and CAL was revealed by multiple logistic regression analysis. (B = 0.374, P = 0.046) CONCLUSIONS: The results revealed a higher prevalence of periodontal viruses such as EBV and CMV in CAD patients with periodontitis suggesting it as one of the risk factors for CAD. This is supported by the fact that severity of periodontal disease (CAL) is associated with the presence of EBV in coronary artery plaque samples in the current study., (© 2020 American Academy of Periodontology.)

Objectives This work describes the design and development of a four-channel near-infrared spectroscopy system to detect the oxygenated and deoxygenated hemoglobin concentration changes in the brain during various motor tasks. Methods The system uses light-emitting diodes corresponding to two wavelengths of 760 nm and 850 nm sensitive to deoxygenated and oxygenated hemoglobin concentration changes, respectively. The response is detected using a photodetector with an integrated transimpedance amplifier. The system is designed with four channels for functional near-infrared spectroscopy (fNIRS) signals acquisition. Two experiments were conducted to demonstrate the ability of the system to detect the changes in hemodynamic responses of different tasks. In the first experiment, the hemodynamic changes during motor execution and imagery of right- and left-fist clenching tasks were acquired by the developed system and validated against a standard multichannel NIRS system. In another experiment, the fNIRS signals during rest and motor execution of right-fist clenching task were acquired using the system and classified. Results The results demonstrate the ability of the designed system to detect the brain hemodynamic changes during various tasks. Also, the activation patterns obtained by the developed system with a minimum number of channels are on par with those obtained by the commercial system. Conclusions The developed four-channel NIRS system is user-friendly and has been designed with inexpensive components, unlike the commercially available NIRS instruments that are cumbersome and expensive.

Introduction: This review evaluates the efficacy and safety of Genvoya® (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide [EVG/c/TAF/FTC]), a single-tablet regimen used for the management of HIV-1 infection. Phase II and III randomized clinical trials evaluate the efficacy and safety of EVG/c/TAF/FTC and tenofovir disoproxil fumerate (TDF)-containing arms; renal impairment, bone mineral density, metabolic effects, and other adverse events are topics explored within this review., Methods: A MEDLINE with full text and PubMed literature search was conducted for the past 5 years, up to April 2016., Results: Virologic suppression was similar between the EVG/c/TAF/FTC and TDF-containing groups (<50 copies/mL) at week 48. The bone mineral density in the hip and spine showed a significant reduction in the TDF-containing groups. The glomerular filtration rate increased in patients in the EVG/c/TAF/FTC arm and there were significant differences in total proteinuria, albuminuria, and tubular proteinuria in patients switching to EVG/c/TAF/FTC. The most common adverse events were diarrhea, nausea, and headache., Discussion: The coformulated Genvoya regimen is well tolerated and effective in treatment-naive and virologically suppressed patients. Data seem to suggest it may also be effective and safe in patients with mild to moderate renal impairment. The lower-dosed single-tablet regimen has significantly reduced bone and renal side effects.

Background: Polyherbalism, an alternative natural-based therapy for various disorders, has been quoted about 1,300 years before in Sharangdhar Samhita. Herbal-based combination therapy stages a vital role for the treatment of type 2 diabetes mellitus (T2DM) and associated complications. The present study aims at developing an Ayurvedic-based polyherbal formulation (ADPHF6) and the assessing its antidiabetic and antioxidant property., Methods: ADPHF6 polyherbal formulation was measured for phytochemical components by qualitative methods. The polyherbal formulation was quantitatively estimated for its phytochemical constituents, i. e. total phenol and flavonoid content. Further, the antioxidant property of ADPHF6 formulation was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging assay, hydrogen peroxide radical scavenging assay and metal chelating assay. α-Amylase and α-glucosidase inhibitory activities of polyherbal formulation were also assessed. ADPHF6 was further analysed for its protective antioxidant property against reactive oxygen species (ROS‾)-induced damage in human lymphocyte DNA and pUC19 plasmid., Results: ADPHF6 polyherbal formulation revealed the presence of phytochemical constituents such as alkaloids, flavonoids, phenols, tannins, terpenoids, saponins and cardiac glycosides in significant levels. Further, it also measured the higher levels of total phenols (473.3±3.05 mg/g) and flavonoid (664±5.29 mg/g) content. Polyherbal formulation also exhibited IC50 values of 49.9±0.15, 65.1±0.10 and 60.1±0.05 mg/mL for 2,2- diphenyl-1-picryl-hydrazyl-hydrate (DPPH), hydrogen peroxide (H2O2) and Fe2+ radical scavenging activities, respectively. ADPHF6 revealed an inhibitory activity (IC50) of 0.67±0.01 and 0.81±0.01 mg/mL for α-amylase and glucosidase, respectively. Pre-treated human peripheral blood lymphocytes with ADPHF6 aqueous extract illustrated enhanced protection against ROS-mediated damage as compared with post-treated groups. DNA nicking assay rendered protective activity against the OH¯ radical-induced DNA damage in supercoiled pUC19 plasmid., Conclusions: Our present study demonstrates that ADPHF6 offers potent inhibitory activity against free radicals as well as digestive enzymes. However, studies should be conducted using in vivo model to further elucidate the effect against free radicals and its anti-hyperglycaemic activity in the management of non-insulin-dependent diabetes.

There has recently been much advancement in the diagnosis, treatment, and research of metabolic disorders, especially diabetes. Current research around the world is focused on finding an alternative source of treatment from natural resources for diabetic management, apart from the available synthetic medicines. The present study is a preliminary study of a polyherbal formulation using edible natural resources and an assessment of its antidiabetic activity. The formulation was screened for its phytochemical constituents, total phenols, flavonoids, and vitamin C content. It was also analyzed for its inhibitory effect against the digestive enzymes α-amylase and α-glucosidase, compared with the standard drug acarbose. The formulation showed the presence of major constituents such as steroids, cardiac glycosides, phenols, flavonoids, and saponins. It also had a high level of phenols (340 ± 2.5 mg/g), flavonoids (235.4 ± 8.3 mg/g), and vitamin C (470.8 ± 16.6 mg/g), and showed a half-maximal inhibitory concentration (IC50) value of 0.41 ± 0.03 mg/mL and 0.51 ± 0.01 mg/mL for amylase and glucosidase, respectively. The results showed that ADJ6 had a significant inhibitory activity on α-amylase and α-glucosidase; however, its inhibitory activity was less than that of acarbose. The plants that are formulated in ADJ6 possess potent antidiabetic activity. Thus, we found that ADJ6 is a potent lead for effective diabetic management; however, an evaluation of the formulation must be illustrated using an in vivo model.

Assessment of musculoskeletal function in individuals with haemophilia has been attempted with clinimetric instruments, which use predetermined domains for assessing the same. This study introduces the application of an instrument, the Canadian Occupational Performance Measure (COPM), which is an open-ended questionnaire that allows patients to prioritize their needs and rate their performance in different tasks of daily living as well as their satisfaction in performing them. To study the utility of COPM in evaluating the musculoskeletal functional status of patients with haemophilia and to assess its effectiveness in planning individualized management plans for them. COPM was administered to 67 individuals with haemophilia aged 10-55 years and the data were compared with functional deficits identified through FISH (Functional Independence Score for Haemophilia). A total of 31 performance difficulties in the areas of self-care (62%), productivity (21%) and leisure (17%) were identified by COPM. All eight domains of FISH were identified in COPM as problems in self-care. In addition to these, COPM identified problems in the areas of productivity and leisure. In 78% of the responses on COPM, there was concordance between the performance and satisfaction scores. However, there was discordance between the two in the remaining 22% of responses. COPM is a useful tool for assessment of musculoskeletal dysfunction in haemophilia. It provides a greater insight into the needs of each patient and helps in planning individualized intervention strategies., (© 2011 Blackwell Publishing Ltd.)

Primary cardiac lymphomas (PCL) are extremely rare, and diffuse large B-cell lymphoma is a highly aggressive subtype. We report a case that was initially diagnosed as chronic right heart dysfunction. Detailed investigations revealed a large lobulated tumour occluding the right atrium, infiltrating the inter-atrial septum, the roof of the left atrium, and the aortic root. Despite adequate surgical debulking and initial successful tricuspid annuloplasty, the patient succumbed to multi-organ failure. Pathological analysis of the resected tumour confirmed a diffuse large B-cell lymphoma with a proliferation rate of 100%. What is unique about this case is the size of this rare cardiac tumour, which we believe to be one of the largest described in the literature for a purely intra-cardiac PCL, its aggressive growth rate, and the relatively mild symptomatology until a late stage of the disease., (© Georg Thieme Verlag KG Stuttgart · New York.)

Endomyocardial fibrosis is an uncommon cause of congestive cardiac failure characterized by severe diffuse thickening of the endocardium, and the overall long-term prognosis of this disease is generally considered poor. We report a case of endomyocardial fibrosis that was initially treated by endocardial resection and mitral valve replacement, which was regularly followed-up. The patient underwent successful repair of a paravalvular leak after a period of 17 years. The treatment of left ventricular endomyocardial fibrosis with associated mitral valve disease by endocardial resection and mitral valve replacement is a good surgical option that provides good long-term results.

During transmyocardial revascularization, cellular destruction of cardiomyocytes occurs as a result of the high-energy laser. However, the features of myocardial cellular destruction are unclear. The present study was undertaken to examine the structural characteristics of cell death in the myocardium following transmyocardial revascularization. Myocardial specimens from 3 male patients who had died within 11 days following laser revascularization were collected within 1 h of death and were analyzed by immunohistochemistry and electron microscopy. For immunohistochemistry, antibodies to pro-apoptotic proteins CPP32 and BAX were used. Immunohistochemical examination demonstrated the presence of cells expressing both CPP32 and BAX along the laser channel. Electron microscopic analysis revealed that the lining surface of laser channels consisted of condensed acellular debris and dead cells. No endothelialization of channels was noted. The lumen of laser channels were surrounded by a rim of acellular debris with several outer concentric rims of cardiomyocytes showing features of cellular destruction. The present study identified features of both necrotic and apoptotic cellular death following laser revascularization.

Regulation of alphavbeta3 and alpha5beta1 integrin function plays a crucial role in atherosclerosis. Possible regulators of integrin-matrix interactions are integrin-binding ADAMs (proteins with a disintegrin- and metalloproteinase-domain), like ADAM-15 and ADAM-9. Molecular interactions between ADAM-15, alpha5beta1, and alphavbeta3 have been demonstrated. ADAM-9 and ADAM-15 were found to be interdependently regulated. This study, therefore, investigated whether the upregulation of integrins alpha5beta1 and alphavbeta3 was correlated with the expression of integrin-binding ADAMs in atherosclerotic processes. Human arterial and venous vascular smooth muscle cells (VSMCs) were incubated with PDGF over different time intervals up to a 3-day culture period. mRNA concentrations, quantified by real-time RT-PCR and normalized to PBGD, of integrins alphavbeta3 and alpha5beta1 were strongly increased after a 12-h PDGF-incubation in arterial and venous VSMC. ADAM-15 and ADAM-9 mRNA production showed a corresponding increase following integrin upregulation after a 24-h incubation period. Western blot anaylsis revealed an increased protein expression of integrins and ADAMs in PDGF-stimulated VSMC. Additionally, mRNA concentrations of atherosclerotic and normal human specimens were quantified by real-time RT-PCR. mRNA of ADAMs and integrins was significantly increased in atherosclerotic arteries compared to normal arteries. Immunohistochemistry of these specimens showed an increased expression and codistribution of both ADAMs and integrins in atherosclerosis. In conclusion, upregulation of ADAM-15 and ADAM-9 in atherosclerosis appears to follow an increase in alpha5beta1 and alphavbeta3 integrins. Since alpha5beta1 and alphavbeta3 are known to promote smooth muscle cell migration and proliferation, upregulation of ADAM-15 and ADAM-9 could balance integrin-matrix interactions and cell migration, thus modulating neointima progression., (Copyright 2003 Wiley-Liss, Inc.)

A case of Ebstein's anomaly as demonstrated by echocardiography and electrophysiological studies is discussed. In view of deterioration in tricuspid regurgitation and right ventricular dysfunction, successful surgical repair employing De Vega's tricuspid annuloplasty along with plication of the atrialised portion of the right ventricle is described. Intraoperative transesophageal echocardiography following the procedure revealed satisfactory repair and a significant decrease in tricuspid regurgitation. This simple technique appears to be effective in patients having anterior leaflet sufficiently large area and motion. Adequate long-term follow-up in a large series of patients is essential to confirm that it is also beneficial and durable.

Plasminogen activator inhibitor-1 (PAI-1) and two-chain high molecular weight kininogen (HKa) exert anti-adhesive properties in vitronectin-dependent cell adhesion. Here, the hypothesis was tested that these anti-adhesive components promote apoptosis in vascular cells. PAI-1 or HKa induced a 2- to 3-fold increase in apoptosis of human umbilical-vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC) adherent to vitronectin, as determined by annexin V-FACS assay, similar to alphav-integrin inhibitor cyclo-(Arg-Gly-Asp-D-Phe-Val)-peptide (cRGDfV). Apoptosis occurred after 12 h incubation and was attributable to caspase 3 activation that in turn induced DNA fragmentation. Induction of apoptosis strongly correlated with the anti-adhesive effect of PAI-1 and HKa on these cells. In contrast, PAI-1 and HKa did not affect fibronectin-dependent adhesion or cell survival. uPA did not influence apoptosis in vitronectin- or fibronectin-adherent cells. In atherosclerotic vessel sections, congruent distribution of vitronectin, PAI-1, HK, and of components of the urokinase plasminogen activator/receptor system with apoptotic cells lining foam cell lesions was demonstrated by immunostaining. These results indicate that inhibition of vitronectin-dependent cell adhesion through PAI-1 and HKa correlates with apoptosis induction in vascular cells mediated through the caspase 3 pathway. Co-distribution of apoptosis with plasminogen activation system components in atherosclerosis exemplifies the significance of anti-adhesive mechanisms and apoptosis for tissue remodeling, such as in neointima development.

A case of invasive pulmonary aspergillosis in a 33-year-old, non-immunocompromised male presenting with lower limb paraplegia is reported. The clinical manifestations, diagnosis, and combined medical and surgical management of this rare condition are described.

An 18-year-old female who presented with features suggestive of pigmented xerodermoid is reported.

Ferdinand Sauerbruch (1875-1951) was a pioneer of thoracic and cardiac surgery and is undoubtedly one of the twentieth century's most outstanding surgeons. Before 1904 operations on the thorax met with fatal complications due to pneumothorax. Sauerbruch developed a pressure-differential chamber that maintained normal respiration and enabled safe operations to be undertaken on the thorax. Together with von Mikulicz, he initiated intrathoracic operations and later developed various surgical procedures on the mediastinum, lungs, pericardium, heart, and esophagus. The simple yet effective techniques of positive-pressure ventilation replaced the expensive, cumbersome negative-pressure chamber. Sauerbruch's latter years were marred by dementia that adversely affected his personality, intellect, and capacity as a surgeon. The unjustifiable toll of increasing patient morbidity and mortality forced authorities to dismiss him in 1949. He died at the age of 76 in Berlin. After almost a century since the advent of the first safe thoracic surgery, the advances in technique and technology have been enormous. A great deal is owed to the inspiration and contributions of Ferdinand Sauerbruch.

This study aimed to investigate the features of cell death occurring in aortocoronary saphenous vein bypass grafts. Human aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of > 75% were explanted from 14 patients at redo coronary artery bypass grafting. Proteins associated with apoptotic pathways were identified immunohistochemically using antibodies to Bcl-2, Fas, BAX, p53 and CPP32. Cells undergoing DNA fragmentation were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). DNA synthesis was investigated using the antibody to proliferating cell nuclear antigen (PCNA). Ultrastructural features of cell death were examined by electron microscopy. Anti-apoptotic (Bcl-2) and pro-apoptotic (Bax, p53, CPP32 and Fas) proteins were expressed throughout the graft wall, but marked differences in the characteristics of cell death were noted between atherosclerotic and non-atherosclerotic areas of the intima. In atherosclerotic areas, pro-apoptotic proteins were widely expressed, but ultrastructural analysis failed to identify cells showing typical features of apoptosis. In these areas, necrotic cells were frequently observed, with negative correlation of Bcl-2 expression with TUNEL. Pro-apoptotic proteins showed no correlation with TUNEL. In contrast, in non-atherosclerotic areas of vein grafts, the expression of both anti-apoptotic (Bcl-2) and pro-apoptotic proteins (p53, Bax and CPP32) correlated with TUNEL. In atherosclerotic areas, non-atherosclerotic intimal areas, and in the underlying media, the numbers of TUNEL+ cells correlated with PCNA positivity. Ultrastructurally, apoptotic bodies and features of necrosis were observed in non-atherosclerotic areas of grafts. The present observations indicate that in atherosclerotic areas, cell death occurs mainly by necrosis, while in non-atherosclerotic areas, cell death occurs by both necrosis and apoptosis. An imbalance between DNA fragmentation and DNA synthesis may contribute to graft instability and failure.

The present study examined the distribution of immunocompetent cells in synthetic vascular grafts in an experimental sheep model. Sixty-two adult Merino sheep underwent synthetic patch closure of a longitudinal arteriotomy in the left common carotid artery. The synthetic patch materials used were gelatin sealed Dacron (n=10), fluoropassivated Dacron (n=10), Fluoropassiv (n=12), polyurethane (n=10), expanded polytetrafluoroethylene (n=10) and carbon-lined expanded polytetrafluoroethylene (n=10). The sheep were sacrificed after four weeks when the prosthetic patches were harvested and fixed in 10% neutral buffered formalin. Transverse sections were taken along the graft and paraffin embedded. Serial sections were stained with cell type specific antibodies to identify T-lymphocytes (CD3(+)), dendritic cells (S-100(+)), endothelial cells (von Willebrand factor(+)) and smooth muscle cells (smooth muscle alpha-actin(+)). All six graft types contained CD3(+) and S-100(+) cells in the neointima, within the synthetic matrix and in the perigraft layer. Three different tissue responses to synthetic materials were observed and the grafts were classified accordingly into three groups: (1) gelatin sealed Dacron, fluoropassivated Dacron and Fluoropassiv; (2) expanded polytetrafluoroethylene and carbon-lined expanded polytetrafluoroethylene; (3) polyurethane. The three synthetic materials in Group 1 showed almost identical reactions with least accumulation of immunocompetent cells within the synthetic material but greater accumulation of immuno-inflammatory infiltrates in the perigraft vascular tissue. In this group, new vessels penetrated into the synthetic material and there was prominent formation of foreign body (giant) cells. Group 2 showed greater accumulation of immunocompetent cells within the synthetic material itself but only sparse immuno-inflammatory infiltrates in the perigraft tissue. Group 3 showed a high degree of inflammatory response within both the synthetic material and the perigraft vascular tissue. These observations demonstrate that immunocompetent cells colonise the synthetic matrix of grafts and accumulate in the perigraft tissue, but inflammatory responses vary in different graft types.

We earlier speculated that antigen-presenting dendritic cells may be involved in the immune reactions leading to saphenous vein bypass graft failure. The purpose of this study was to confirm whether dendritic cells are present in stenotic human saphenous vein bypass grafts. Segments of stenotic saphenous vein grafts were explanted from 14 patients at re-do bypass operation and ten normal saphenous veins were harvested during femoro-popliteal grafting. Sections of specimens were analysed using cell type specific antibodies to identify dendritic cells (CD1a, S-100), T-lymphocytes (CD3), macrophages (CD68), smooth muscle cells (alpha-SMA) and endothelial cells (FVIII). Dual immunostaining, confocal immunofluorescent laser scanning microscopy and electron microscopy were used. Stenotic grafts showed structural alterations of intimal hyperplasia and varying degrees of atherosclerotic degeneration. No cells expressing CD1a and S-100 were observed in the intima and media of normal saphenous veins. Cells expressing these antigens were present around areas of medial neovascularization and within intimal atherosclerotic lesions in saphenous vein bypass grafts. Electron microscopy demonstrated the presence of cells containing a well-developed tubulovesicular system which is unique to cells from the dendritic cell family. Double immunohistochemistry and confocal immunofluorescent microscopy revealed the co-localization of T-lymphocytes with dendritic cells. Dendritic cells are present in stenotic saphenous vein bypass grafts. Dendritic cells may be responsible for antigen presentation and modulation of immune reactions in accelerated graft atherosclerosis through their interaction with T-lymphocytes.

Background and Aim of the Study: Transmyocardial laser revascularization (TMR) has demonstrated significant relief in patients presenting with refractory angina. However, the mechanism by which TMR improves clinical symptoms is unclear. This study analyzes the early immunohistochemical and ultrastructural features of the human myocardium following TMR., Methods: Specimens of myocardium that contained laser channels were removed in toto at autopsy from three male patients, ages 41, 57, and 65 (mean age 55.8) who had died 1 to 11 days (mean 6.8) following laser revascularization. Consecutive parallel sections of specimens were stained with cell-type specific antibodies to CD3 (to identify T-lymphocytes), CD68 (macrophages), Factor VIII (endothelial cells), and myosin (myocytes). Additionally, adjacent areas of myocardium that contained laser channels were processed and analyzed by transmission electron microscopy., Results: The internal lining surface of laser channels was composed of vacuolized and condensed myocardial debris. No obvious connections were noted between laser channels and the ventricular cavity. No endothelialization of channels was observed, whereas the adjacent noninjured myocardium demonstrated microvessels lined by well-preserved endothelial cells. The laser channels were surrounded by zones of necrotic cardiomyocytes., Conclusions: Our observations suggest that laser channels are not lined by endothelial cells during the early stages following TMR. Mechanisms other than direct myocardial perfusion from the ventricular cavity by patent endothelialized channels may explain the immediate relief from angina provided by TMR.

The aim of this study was to analyze the cellular composition of the arterial wall in Takayasu's disease and to investigate the contribution of the various cell types to the immunoinflammatory processes and degenerative alterations of the vessel wall in this disease. Specimens of aorta were obtained at operation from 10 patients with Takayasu's arteritis. The duration of disease ranged from 2 months to 13 years. Immunohistochemical investigation was carried out using the antibodies CD3 (to identify T-cells), CD20 (B-cells), S-100 (dendritic cells), CD68 (macrophages), CD15 (granulocytes), von Willebrand factor (endothelial cells), and alpha-smooth muscle actin (smooth muscle cells). All specimens showed distinctive histologic features of Takayasu's arteritis and contained inflammatory infiltrates, but the degree of their accumulation within the aortic wall varied. Inflammatory infiltrates within the deep part of the intima, around areas of neovascularization and within the adventitia contained T-cells colocalizing with dendritic cells. Nodules formed by large numbers of intermingling T-cells and B-cells enriched with dendritic cells were observed in the adventitia. Massive accumulation of granulocytes and their destruction within the adventitia were prominent in all cases. This is the first study that establishes the presence of dendritic cells and granulocytes in Takayasu's disease. Dendritic cells are probably involved in the immunoinflammatory processes through their interaction with T-cells and B-cells. The present observations may help understanding of the pathogenesis of Takayasu's disease.

Following implantation different cell types interact with synthetic vascular prostheses resulting in a complex immuno-inflammatory response. Dendritic cells are responsible for activating the primary T-lymphocyte immune response in various pathological conditions by their role as antigen-presenters. This study aimed at examining whether dendritic cells accumulate within small diameter expanded polytetrafluoroethylene (ePTFE, Goretex(R)) grafts explanted from humans. Segments of expanded polytetrafluoroethylene were explanted from 11 patients (6 male, 5 female), aged between 60 and 83 years (mean 70.7 years) at secondary or revision bypass operation. The graft implant duration varied from 4 months to 12 years (mean 40.5 months). Dendritic cells were identified immunohistochemically using S-100 antibody, as well as by electron microscopy. Immunohistochemical examination showed that all 11 explanted synthetic grafts contained S-100(+) cells colonising both the synthetic matrix itself, and the adjacent perigraft tissue. Electron microscopic analysis confirmed the presence of cells with a characteristic dendritic cell morphology within the grafts. Dendritic cells which accumulated within synthetic grafts were found to co-localise with T-lymphocytes. Based on these observations, we speculate that dendritic cells may be involved in the immuno-inflammatory responses following the implantation of synthetic vascular prostheses through their interaction with T-lymphocytes.

Dendritic cells are specialised leucocytes responsible for capturing and presenting antigens to T lymphocytes, which in turn mediate immune responses in various pathological conditions. The observations in this study demonstrate that dendritic cells are present in stenotic aortocoronary saphenous vein bypass grafts, which suggest that these cells may be involved in inflammatory actions which may subsequently contribute to graft failure.

Aortocoronary saphenous vein bypass grafts undergo structural alterations within the arterialized vein, resulting in graft stenosis and failure. Areas of the acellular intima contribute to fissuring, cracking and ulceration, while areas of the media become highly vascular but thinned. This study aimed to examine the ultrastructural features of cell death, including apoptosis and necrosis, in non-atherosclerotic areas of the stenotic aortocoronary saphenous vein bypass grafts. Thirteen stenotic vein grafts were obtained at redo coronary artery bypass grafting. The ultrastructural features of cell death were analysed by electron microscopy. Typical features of necrosis, including focal areas of cytoplasmic oedema, plasmalemmal destruction and nuclear condensation with cytoplasmic organelle destruction, were observed throughout the intima and media. Features of apoptosis, including the presence of apoptotic bodies, were also identified in the hyperplastic intima and its adjacent media. Our observations suggest that both apoptosis and necrosis occur in non-atherosclerotic areas of stenotic aortocoronary saphenous vein bypass grafts.

The present study was undertaken to examine the cellular composition of the aortic wall in Takayasu's arteritis and to investigate the association of different cell types in the immuno-inflammatory reactions of this disease. Specimens of aortic wall affected by Takayasu's arteritis were obtained from 10 patients (five male, five female), aged 32 to 68 years (mean 49.5 years) at elective operation. The mean duration of disease was 6.5 years (range 2 months to 13 years). Specimens were embedded in paraffin and the sections stained with antibodies to CD3 (to identify T cells), CD20 (B cells), S-100 (dendritic cells), CD15 (granulocytes), CD68 (macrophages), alpha-SMA (smooth muscle cells) and von Willebrand factor (endothelial cells). Immunohistochemical examination demonstrated that all specimens showed histological alteration with the replacement of the muscular and elastic layers of the media and adventitia by dense fibrous tissue, and were characterized by varying degrees of inflammatory cell infiltration. In five cases, inflammatory nodules consisting of numerous T cells and B cells were observed in the adventitia. Within the inflammatory nodules, as well as around areas of neovascularization in the deep portion of the intima, lymphocytes were co-localized with dendritic cells. In addition, in the adventitia, the accumulation of a large number of granulocytes was observed. The present study demonstrates that immune inflammation is a typical feature of Takayasu's disease, and that the interactions between dendritic cells and lymphocytes may be important in the control of the immune reactions in this vascular pathology.

Objective: The present work aimed to investigate how the Ca(2+)-dependent cell adhesion molecule vascular endothelial (VE)-cadherin might be involved in atherogenesis., Methods: Specimens of human carotid artery and aorta were obtained at operation. An immunohistochemical approach using cell-type specific antibodies examined how VE-cadherin expression in areas of neovascularisation related to the accumulation of immunocompetent and inflammatory cells within atherosclerotic plaque. Electron microscopy was used to examine the structural characteristics of neovessels and the cell composition in the surrounding intimal matrix., Results: In all the non-atherosclerotic aortic segments, VE-cadherin expression was observed only in the adventitia and the outer third of the media. Within the atherosclerotic arterial segments, VE-cadherin was expressed in all layers of the arterial wall including the intima where VE-cadherin was expressed by endothelial cells in areas of neovascularization. In some neovessels, loss of VE-cadherin expression was associated with increased focal accumulation of T-cells, macrophages and dendritic cells. Electron-microscopic examination demonstrated varying degrees of endothelial continuity in the intimal neovessels. Within those neovessels which were surrounded by a large number of immunocompetent and inflammatory cells, some inter-endothelial cell contacts were open allowing the penetration of blood cells through patent intercellular zones., Conclusions: VE-cadherin is expressed in atherosclerotic lesions by endothelial cells associated with neovascularisation. Downregulation of VE-cadherin expression within some intimal neovessels is accompanied by increased entry of immunocompetent cells into the intimal matrix surrounding areas of neovascularization which suggests that disorganizing endothelial cell-to-cell interactions within neovessels is significant in atherogenesis.

Antigen-presenting dendritic cells are present in atherosclerotic lesions in human arterial intima, but have not been investigated in atherosclerotic and hyperplastic stenotic lesions that affect vein grafts used as arterial conduits. This study was undertaken to examine whether dendritic cells are present in aortocoronary artery saphenous vein bypass grafts affected by high-grade atheromatous stenosis. Stenotic saphenous vein coronary artery bypass grafts (angiographic luminal stenosis > 75%) were harvested from 10 patients (nine male, one female), aged 4271 years (mean 56.5) at re-do operation. The mean time interval from bypass surgery to the excision of stenotic grafts was 11.5 years (range 2-21). The specimens were fixed in 10% buffered formalin, embedded in paraffin blocks and the sections stained with antibodies to S-100 (to identify dendritic cells), CD3 (T cells), CD68 (macrophages), von Willebrand factor (endothelial cells) and alpha-smooth muscle actin (smooth muscle cells) using avidin-biotin complex immunoperoxidase technique. Normal veins were obtained during saphenous vein femoro-popliteal grafting. The stenotic venous grafts showed histological features typical of extensive arterialization, intimal hyperplasia, atherosclerotic plaque-like lesions, calcification and thrombosis. In areas of intimal hyperplasia, S-10O-positive cells were distributed irregularly among smooth muscle cells. S-100-positive dendritic cells were seen most frequently within atherosclerotic plaque-like lesions where they co-localized with CD3+ cells and CD68+ cells. S-100-positive dendritic cells were also seen accumulating within calcific foci. No S-100-positve cells were found in normal, ungrafted saphenous veins. We conclude that dendritic cells are present in aortocoronary saphenous vein bypass grafts affected by high grade stenosis. Dendritic cells are probably involved in immune mechanisms of atherogenesis through their interactions with T cells and macrophages. The accumulation of dendritic cells within calcific foci suggests their contribution to the calcification of stenotic venous grafts.

Aortocoronary saphenous vein bypass grafts fail because of structural pathologies (thrombosis, intimal hyperplasia and atherosclerosis) within the 'arterialized' vein leading to graft stenosis. This study examined structural characteristics of atherosclerotic alterations in long-term aortocoronary artery saphenous vein bypass grafts with particular attention to the features of cell death in atherosclerotic lesions. Stenotic vein grafts were obtained from 10 patients at redo coronary artery bypass grafting operations. All the grafts were affected by histological abnormalities, with eight out of ten grafts showing evidence of atherosclerotic alterations in the intimal hyperplastic layer. Areas containing foam cells were examined by electron microscopy. Cells with cytoplasmic lipid accumulations were characterized by varying degrees of chromatin condensation, fragmentation or dispersion, by focal areas of oedema and vacuolisation of their cytoplasm, and by plasmalemmal destruction. Some lipid-filled cells exhibiting signs of destruction contained myofilaments and basal membrane fragments, allowing them to be identified as smooth muscle cells. Macrophage foam cells were found to have undergone similar destruction. No cells showing nuclear degeneration were observed to have intact cytoplasmic organelles. Neither were apoptotic bodies identified, but necrotic remnants were frequently seen. The results suggest that cell death in atherosclerotic lesions affecting aortocoronary artery saphenous vein bypass grafts occurs through oncosis rather than by apoptosis.

Dendritic cells are potent antigen-presenting cells responsible for the activation of T-lymphocytes in various immune responses. Their role in the initiation of immune reactions in allergies, autoimmune diseases, tumors, transplantation, and, more recently, in atherosclerosis has been well established, but their involvement in venous pathologies has not been previously investigated. The aim of this study was to determine whether dendritic cells are present in veins affected by varicosity and thrombophlebitis. Three groups of veins obtained at operation were studied: (1) varicose veins of the great saphenous vein from patients who were undergoing vein stripping for primary varicosity; (2) segments of the great saphenous vein from patients with varicosity complicated by thrombophlebitis; and (3) great saphenous veins without varicosity or thrombophlebitis from patients who were undergoing femoropopliteal bypass grafting. The specimens were fixed in 10% neutral buffered formalin and embedded in paraffin, and the sections were stained with antibodies to S-100 (to identify dendritic cells), CD3 (T-lymphocytes), CD68 (macrophages), von Willebrand factor (endothelial cells), alpha-smooth muscle actin (smooth muscle cells), and CD15 (mast cells) by use of avidin-biotin complex (ABC) immunoperoxidase technique. Immunohistochemical examination showed that no S-100-positive dendritic cells were present in normal saphenous veins. In contrast, S-100-positive cells with dendritic cell morphology were detected in the intima and media of veins with varicosity and thrombophlebitis, where they represented a minor cell population. S-100-positive dendritic cells were located between smooth muscle cells as well as around areas of neovascularization where they colocalized with T-lymphocytes. The present work suggests that dendritic cells might be involved in pathological processes in veins affected by varicosity and thrombophlebitis. The authors speculate that dendritic cells may be involved in the inflammatory mechanisms in these veins through their interaction with T-lymphocytes.