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We report an near-infrared (NIR)-trackable and therapeutic liposome with skin tumor specificity. Liposomes with a hydrodynamic diameter of ∼20 nm are tracked under the vein visualization imaging system in the presence of loaded paclitaxel and NIR-active agents. The ability to track liposome nanocarriers is recorded on the tissue-mimicking phantom model and in vivo mouse veins after intravenous administration. The trackable liposome delivery provides in vitro and in vivo photothermal heat (∼40 °C) for NIR-light-triggered area-specific chemotherapeutic release. This approach can be linked with a real-time vein-imaging system to track and apply area-specific local heat, which hitchhikes liposomes from the vein and finally releases them at the tumor site. We conducted studies on mice skin tumors that indicated the disappearance of tumors visibly and histologically (H&E stains). The ability of nanocarriers to monitor after administration is crucial for improving the effectiveness and specificity of cancer therapy, which could be achieved in the trackable delivery system.

Objective: This cross-sectional study aimed to investigate the association between high cholesterol levels and the prevalence of periodontal disease among patients in the United States, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2017 and 2020. We hypothesize that patients with high cholesterol levels will have a high prevalence of periodontal disease., Methods: The study utilized a cross-sectional design, analyzing data from NHANES 2017-March 2020 pre-pandemic survey, a nationally representative survey. The sub-sample consisted of 7,042 participants aged 30 years and older who underwent the NHANES survey questionnaire. Information on high cholesterol levels and periodontal disease was obtained through self-reported data. Statistical analyses, using SAS 9.4 (SAS Institute Inc., Cary, NC), were performed to assess the association between high cholesterol levels and periodontal disease prevalence while controlling the potential confounding variables. Descriptive statistics and multivariable logistic regression were used.  Results: The study included a total of 7,042 participants. The mean age (SD) of the participants was 60.2 (13.7); 54% were females and 46% were males. Out of the total, 23% (1636) of the samples had periodontal disease and 52% (3669) of the participants had high cholesterol levels. Findings indicated a significant association between high cholesterol and periodontal disease (odds ratio, OR = 1.21, 95% confidence interval, CI = 1.06-1.40). Socioeconomic factors such as poverty and education, and other factors such as age, gender, race, smoking, physical activity, BMI, diabetes, hypertension, sugar intake, cholesterol intake, saturated fatty acids intake, and oral hygiene were identified as potential confounders., Conclusion: This large-scale cross-sectional study investigated the association between high cholesterol and periodontal disease while comprehensively controlling for potential confounding factors. After adjusting for the relevant confounders, we found a weak positive association between high cholesterol and periodontal disease. While these findings provide valuable insights into the interplay between systemic health and oral health, the cross-sectional nature of the study limits the establishment of causality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Khan et al.)

Objective: This cross-sectional study aimed to investigate the association between seeking urgent dental care and the prevalence of root caries among patients in the United States, utilizing data from the Nutritional Health and Examination Survey (NHANES) conducted between 2017 and 2020. Our hypothesis is that patients who are seeking urgent dental care due to pain will have a high prevalence of root caries., Methods: The study utilized a cross-sectional design, analyzing data from NHANES 2017-March 2020 pre-pandemic data, a nationally representative survey. The sub-sample consisted of 6,186 participants aged 20 years and older who underwent oral health assessments, including the examination of root caries. Information on seeking urgent dental care was obtained through self-reported data. Statistical analyses, using SAS 9.4 (SAS Institute Inc., Cary, NC), were performed to assess the association between urgent care seeking and root caries prevalence while controlling the potential confounding variables. Descriptive statistics and multivariable logistic regression were used.  Results: The study included a total of 6,186 participants. The mean age (SD) of the participants was 49.7 (17.2). Some 52% were females and 48% were males. Some 14% (849) of the samples had root caries and 28% (1739) of the participants were seeking urgent dental care due to pain. Findings indicated a significant association between seeking urgent dental care and the prevalence of root caries (odds ratio, OR = 2.72, 95% confidence interval, CI = 2.32-3.18). Individuals who reported seeking urgent care had a higher prevalence of root caries (26% vs. 9%) compared to those who did not seek urgent care. Socioeconomic factors such as poverty and education, and other factors such as age, gender, race, marital status, and alcohol intake were identified as potential confounders., Conclusion: This study provides evidence of the association between seeking urgent dental care and the prevalence of root caries among patients in the United States. The findings underscore the importance of promoting regular dental visits, preventive measures, and early interventions to mitigate the risk of root caries among individuals seeking urgent dental care. Addressing socio-economic barriers, improving access to dental services, and enhancing oral health education are crucial steps toward reducing the burden of root caries in this population. Further, longitudinal studies are recommended to establish the temporal relationship between urgent care seeking and root caries development., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mobin et al.)

The recent discovery of the horizontal transfer of a toxin-neutralizing gene from plant to whitefly (Bemisia tabaci), a polyphagous insect, sparked a new area of study. In this forum, we discuss some potential biotechnological applications of this newly discovered knowledge in the coevolutionary arms race between plants and whitefly., Competing Interests: Declaration of interests The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background One of the biggest hurdles in treating pediatric patients is managing dental fear and anxiety. Some factors that contribute to an increase in dental anxiety are fear of pain, the presence of unknown individuals, a change in the setting of an environment, and separation from parents. Aim The aim of this study was to evaluate dental fear and anxiety in pediatric patients, between the ages of 6 and 12 years, visiting private and public dental hospitals using the Children's Fear Survey Schedule-Dental Subscale (CFSS-DS). Methods A total of 280 children, 140 in a private dental hospital setting and 140 in a public dental hospital setting, were enrolled in this study. The purpose of the study was explained to the accompanying guardian of the patient and written consent was taken. The CFSS-DS was explained verbally in Urdu and the questionnaire was given to guardians alongside the patients which they were asked to fill out following their dental treatment. Result The data obtained from the questionnaires were analyzed using the unpaired t-test. The highest dental fear mean scores and standard deviation in a private dental hospital were for "choking" (3.25 ± 1.21), "the noise of the dentist drilling" (3.24 ± 1.04), and "having somebody put instruments in your mouth" (3.19 ± 1.06), whereas, for a public dental hospital, the highest fear score was recorded in "choking" (3.17 ± 1.69), "injections" (3.07 ± 1.72), and "people in white uniforms" (1.90 ± 1.21). Conclusion The study showed a higher prevalence of dental fear and anxiety in a private dental setting when compared to a public dental setting. Factors responsible for an increase in dental fear need to be assessed for each patient and then treatment given accordingly., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mobin et al.)

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis. However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Hypertriglyceridaemia represents one of the most prevalent lipid abnormalities, however it is often eclipsed by focus on LDL cholesterol and is frequently overlooked by clinicians, despite it being an important cardiovascular risk factor. For most patients, hypertriglyceridaemia arises from a combination of environmental factors and multiple genetic variations with small effects. Even in cases with apparent familial clustering of hypertriglyceridaemia, a monogenetic cause is rarely identified. Common secondary causes include obesity, uncontrolled diabetes, alcohol, and various commonly used drugs. Correction of these factors, along with lifestyle optimisation, should be prioritised prior to commencing medication. The goal of drug treatment is to reduce the risk of cardiovascular disease in those with moderate hypertriglyceridaemia and the risk of pancreatitis in those with severe hypertriglyceridaemia. Recent and ongoing trials demonstrate the important role of triglycerides (TG) in determining residual risk in patients with cardiovascular disease (CVD) already established on statin therapy. Novel and emerging data on omega-3 fatty acids (high-dose icosapent ethyl) and the selective PPAR modulator pemafibrate are eagerly awaited and may provide further clarity for clinicians in determining which patients will benefit from TG lowering and help inform clinical guidelines. There are numerous novel therapies on the horizon that reduce TG by decreasing the activity of proteins that inhibit lipoprotein lipase such as apolipoprotein C-III (including Volanesorsen which was recently approved in Germany) and ANGPTL 3/4 which may offer promise for the future., (Copyright ©2021 The Author(s).)

Aims: An abundance of epidemiological evidence demonstrates that elevated lipoprotein(a) (Lp(a)) represents a significant contributing risk factor towards the development of cardiovascular disease. In particular, raised Lp(a) may play a mechanistic role in patients with refractory angina. Studies have also shown a correlation between oxidised LDL (oxLDL) levels and atherosclerotic burden as well as rates of cardiovascular events. Antibodies against oxLDL (anti-oxLDL) are involved in the removal of oxLDL. Lipoprotein apheresis (LA), which removes lipoproteins using extra-corporeal processes, is an established means of reducing Lp(a), and thereby reduces cardiovascular events. The aim of this study was to investigate the effect of LA on oxLDL and anti-oxLDL levels amongst those with refractory angina in the context of raised Lp(a). Methods: We performed a sub-study within a randomised controlled crossover trial involving 20 patients with refractory angina and raised Lp(a) > 500 mg/L, comparing the effect of three months of blinded weekly LA or sham, followed by crossover to the opposite study arm. We utilized enzyme-linked immunosorbent assays (ELISA) to quantify oxLDL and IgG/ IgM anti-oxLDL antibody levels at baseline and following three months of active LA or sham sessions. Results: Following three months of LA, there was a 30% reduction in oxLDL from 0.37 ± 0.06 to 0.26 ± 0.04 with a mean drop of -0.11 units (U) (95% CI -0.13, -0.09) compared to no significant change with sham therapy ( p < 0.0001 between treatment arms). LA also led to a 22% reduction in levels of IgG and IgM anti-oxLDL, again with no significant change demonstrated during sham ( p = 0.0036 and p = 0.012, respectively, between treatment arms). Conclusion: Amongst patients with refractory angina in the context of elevated Lp(a), LA significantly lowers levels of oxLDL and anti-oxLDL antibodies, representing potential mechanisms by which LA yields symptomatic and prognostic benefits in this patient cohort.

Introduction: Genetic testing for familial hypercholesterolaemia (FH) is not yet established for widespread use internationally to provide diagnostic confirmation, in part due to high cost and resource requirement. We need to establish whether genetic testing is clinically justified in terms of risk stratification and prediction of cardiovascular events. Methods: We performed a single tertiary cardiac centre retrospective evaluation of patients with FH managed within our genetic screening service. We evaluated the prevalence of cardiovascular events in genetically confirmed cases of FH compared to those unconfirmed upon genetic testing, to assess whether gene positivity confers a higher risk phenotype. We also compared the clinical characteristics of the genetically confirmed and unconfirmed group. Results: Amongst adult patients (≥18 years) with genetically confirmed heterozygous FH (n=87), 34% (30/87) had one or more documented CV events. In comparison a lower event rate was observed in adult patients with genetically unconfirmed FH (n=170) with 25% (42/170) experiencing one or more documented CV events. Additional cardiovascular risk factors were more prevalent in the unconfirmed group including hypertension, co-morbidities, higher age and body mass index which may have modified the difference in cardiovascular risk. Conclusion: Genetic testing in FH may be clinically justified and appears to identify a subset of patients with higher risk of cardiovascular events. However, the risk difference is modified by alternative cardiovascular risk factors and co-morbidities which may be more prevalent in genetically unconfirmed FH., (Copyright ©2020 The Author(s).)

Background: Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis., Objectives: The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a)., Methods: In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a) > 50 mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for in vitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1 + 2, and thrombin generation assays., Results: Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P = .0001) but not by sham (P = .0001 between treatment arms). Apheresis prolonged occlusion time (576 ± 116 s vs 723 ± 142 s, P < .0001) reflecting reduced platelet reactivity and reduced lysis time (1340 [1128, 1682] s vs 847 [685,1302] s, P = .0006) reflecting enhanced fibrinolysis, without corresponding changes with sham. Apheresis, but not sham, reduced von Willebrand Factor (149 [89.0, 164] vs 64.2 [48.5, 89.8] IU/dL, P = .0001), and fibrinogen (3.12 ± 0.68 vs 2.20 ± 0.53 g/L, P < .0001), and increased prothrombin fragments 1 + 2 (158.16 [128.77, 232.09] vs 795.12 [272.55, 1201.00] pmol/L, P = .0006). There was no change in D-dimer, thrombin/anti-thrombin III complex, or thrombin generation assay with apheresis or sham., Conclusion: Lipoprotein apheresis reduces Lp(a) and improves some thrombotic and fibrinolytic parameters in patients with refractory angina., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Aims: To determine the clinical impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a) > 500 mg/L on the primary end point of quantitative myocardial perfusion, as well as secondary end points including atheroma burden, exercise capacity, symptoms, and quality of life., Methods: We conducted a single-blinded randomized controlled trial in 20 patients with refractory angina and raised lipoprotein(a) > 500 mg/L, with 3 months of blinded weekly lipoprotein apheresis or sham, followed by crossover. The primary endpoint was change in quantitative myocardial perfusion reserve (MPR) assessed by cardiovascular magnetic resonance. Secondary endpoints included measures of atheroma burden, exercise capacity, symptoms and quality of life., Results: The primary endpoint, namely MPR, increased following apheresis (0.47; 95% CI 0.31-0.63) compared with sham (-0.16; 95% CI - 0.33-0.02) yielding a net treatment increase of 0.63 (95% CI 0.37-0.89; P < 0.001 between groups). Improvements with apheresis compared with sham also occurred in atherosclerotic burden as assessed by total carotid wall volume (P < 0.001), exercise capacity by the 6 min walk test (P = 0.001), 4 of 5 domains of the Seattle angina questionnaire (all P < 0.02) and quality of life physical component summary by the short form 36 survey (P = 0.001)., Conclusion: Lipoprotein apheresis may represent an effective novel treatment for patients with refractory angina and raised lipoprotein(a) improving myocardial perfusion, atheroma burden, exercise capacity and symptoms., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Angina that is refractory to conventional medical therapy and revascularisation, remains challenging to manage and poses significant burden to patients. Elevated lipoprotein(a) [Lp(a)] has emerged as an important independent cardiovascular risk factor and predictor of adverse outcomes in atherosclerotic disease. The prevalence of raised Lp(a) amongst patients with refractory angina has not yet been defined., Objective: To establish the prevalence of raised [Lp(a)] >500 mg/L in patients with refractory angina., Methods: We conducted an epidemiological screening pilot study in 75 patients with refractory angina from a UK tertiary cardiac centre. We determined the proportion of the cohort with raised Lp(a) >500 mg/L using an isoform-insensitive method. In addition, a full fasting lipid profile (including: LDL cholesterol, HDL cholesterol, total cholesterol to HDL ratio and triglycerides) was obtained. Patients were also asked about the presence of conventional cardiovascular risk factors., Results: Our study demonstrated that 60% of the 75 patients with refractory angina had raised Lp(a) levels of >500 mg/L. The median and inter-quartile range of Lp(a) values were 771 mg/L (162 mg/L,1260 mg/L) respectively., Conclusions: This high prevalence of raised Lp(a) detected in our cohort with refractory angina may suggest a causal role. Further research is necessary to confirm this association and prospective studies are needed to explore the potential therapeutic benefit of Lp(a) reduction in patients with refractory angina.

It is well established that Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor and predictor of major adverse cardiovascular events. Lipoprotein apheresis is currently the most effective approved treatment available, with minimal effect conferred by conventional lipid lowering agents. A growing body of evidence suggests that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although more prospective research is required in this field. Angina which is refractory to conventional medical therapy and revascularisation is extremely challenging to manage. There is a significant unmet need to establish therapeutic options. Our goal is to determine the impact of lipoprotein apheresis on clinical parameters and symptoms of patients with refractory angina secondary to advanced coronary disease and raised Lp(a). Determining whether we should aggressively lower Lp(a) in such patients remains a very important question, which could potentially impact on the management of a large population. We will also gain insight into how this treatment works and the mechanisms via which Lp(a) increases cardiovascular risk. We are currently conducting a prospective, randomised controlled crossover study of patients with refractory angina and raised Lp(a), randomised to undergoing three months of weekly lipoprotein apheresis or sham apheresis. Patients will then crossover to the opposite study arm after a 1 month wash-out phase. We will assess myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised LDL and their antibodies, exercise capacity, angina and quality of life at the beginning and end of treatment, to determine the net true treatment effect on the above parameters. This is a novel area of research, as previous studies have not assessed the role of lipoprotein apheresis in patients with refractory angina and raised Lp(a) in a prospective randomised controlled manner., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

It is increasingly recognised that lipoprotein(a) [Lp(a)], an inherited, genetically-determined form of LDL-cholesterol, is an independent cardiovascular risk factor and predictor of adverse cardiovascular outcomes. Lp(a) is felt to increase cardiovascular risk via its pro-thrombotic effect and by enhancing intimal lipoprotein deposition. Lipoprotein apheresis is currently the most effective treatment for raised Lp(a). There is a growing body of evidence suggesting that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although much more research is required in this field. Angina which is refractory to conventional medical therapy and revascularisation, is extremely challenging to manage. Treatment options for such patients remain very limited. We describe the case of a patient with refractory angina and raised lipoprotein(a) in whom aggressive reduction of Lp(a) with lipoprotein apheresis successfully ameliorated the progression of coronary stenosis and provided effective and durable relief of angina symptoms. In our centre, we are currently conducting a prospective, randomised controlled cross-over study of patients with refractory angina and raised Lp(a), randomised to undergoing lipoprotein apheresis or 'sham' apheresis with assessment of myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised phospholipids and their antibodies, exercise capacity, angina symptoms and quality of life at the beginning and end of treatment.

Accessing ultrafast photoinduced molecular dynamics on a femtosecond time-scale with vibrational selectivity and at the same time sub-diffraction limited spatial resolution would help to gain important information about ultrafast processes in nanostructures. While nonlinear Raman techniques have been used to obtain highly resolved images in combination with near-field microscopy, the use of femtosecond laser pulses in electronic resonance still constitutes a big challenge. Here, we present our first results on coherent anti-Stokes Raman scattering (fs-CARS) with femtosecond laser pulses detected in the near-field using scanning near-field optical microscopy (SNOM). We demonstrate that highly spatially resolved images can be obtained from poly(3-hexylthiophene) (P3HT) nano-structures where the fs-CARS process was in resonance with the P3HT absorption and with characteristic P3HT vibrational modes without destruction of the samples. Sub-diffraction limited lateral resolution is achieved. Especially the height resolution clearly surpasses that obtained with standard microCARS. These results will be the basis for future investigations of mode-selective dynamics in the near field.

Successful correction of bronchial compression and severe bronchomalacia complicating repair of interrupted aortic arch was achieved using transverse aortic arch extension with a pulmonary artery autograft and left bronchial sleeve resection. This procedure increased space within the aortic arch and eliminated bronchial narrowing with excellent results.

Idiopathic pulmonary fibrosis (IPF) and bronchiolitis obliterans with organizing pneumonia (BOOP) are interstitial lung diseases of unknown pathogenesis. Alveolar macrophages play a major role in the regulation of the inflammatory response in these diseases through their ability to produce cytokines that modify the inflammatory response. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) exhibit proinflammatory and anti-inflammatory actions, respectively, and thus an imbalance in the expression of these cytokines may contribute to the pathogenesis of IPF and BOOP. Therefore, we quantified IL-10 and TNF-alpha mRNA levels in alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with IPF and BOOP and in normal healthy volunteers. The level of TNF-alpha mRNA in macrophages obtained from IPF and BOOP patients was not significantly different from normal healthy subjects. However, macrophages from patients with IPF and BOOP expressed increased levels of IL-10 mRNA compared with healthy controls. In addition, stimulation of alveolar macrophages with lipopolysaccharide in the presence of a neutralizing anti-IL-10 antibody augmented the production of TNF-alpha over that seen in the absence of anti-IL-10 antibody, suggesting that the increased expression of IL-10 by alveolar macrophages may act to control the expression of TNF-alpha. Paradoxically, measurement of IL-10 protein in cell-free BAL fluid revealed lower amounts of the protein in patients with IPF and BOOP compared with healthy controls.

Airway inflammation in children younger than 5 yr of age is difficult to assess, particularly in patients with cystic fibrosis (CF). Furthermore, determining responses to therapies is often subjective in infants, especially those with CF. To determine whether airway DNA levels could be used as an index of airway inflammation, we measured DNA levels in bronchoalveolar lavage fluid (BALF), using a Hoechst dye-binding assay. BALF DNA levels and neutrophils from 16 infants with CF were compared with levels obtained from seven older CF patients and nine control children who underwent bronchoalveolar lavage for evaluation of other pulmonary diseases. BALF DNA was increased in both infants (3.2 +/- 0.7 microg/ml) and older patients with CF (5.4 +/- 0.9 microg/ml) compared with the controls (0.7 +/- 0.2 microg/ml) (mean +/- SEM). BALF DNA levels were not significantly different between infants and older patients with CF. BALF neutrophil counts in CF patients were significantly higher than in controls. Furthermore, BALF DNA levels and total neutrophil counts in infants with CF correlated positively with one another. We conclude that: (1) DNA levels were easily quantifiable in BALF of young children; (2) DNA levels in BALF from CF patients were greater than in a group of children with other pulmonary diseases, and that in some infants with CF, BALF DNA levels were equivalent to those of much older patients with CF; (3) DNA levels in BALF correlate with BALF neutrophil number, an index of inflammation; and (4) some infants with CF have increased levels of DNA in BALF, which may justify a clinical trial of aerosolized rhDNase in this population.

The mechanisms underlying the initiation of lung disease and early respiratory morbidity in cystic fibrosis (CF) are poorly understood. By identifying infants with CF through a statewide neonatal screening program, we investigated whether airway inflammation was present in these infants, with the goal of furthering our understanding of the early events in this lung disease. Bronchoalveolar lavage fluid (BALF) from 16 infants with CF (mean age, 6 mo) and 11 disease control infants (mean age, 12 mo) was examined for the following inflammatory parameters: (1) neutrophil count; (2) activity of free neutrophil elastase; (3) elastase/alpha 1-antiprotease inhibitor complexes; and (4) the level of interleukin-8 (IL-8). We also quantified the spontaneous level of expression of IL-8 mRNA transcripts by airway macrophages. Each index of airway inflammation was increased in the BALF of infants with CF as compared with control infants. In addition, both the number of neutrophils and IL-8 levels were increased in infants with CF who had negative cultures (n = 7) for common bacterial CF-related pathogens, as well as for common respiratory viruses and fungi at the time of bronchoalveolar lavage (BAL). These findings suggest that airway inflammation is already present in infants with CF who are as young as 4 wks. Furthermore, although many different cell types (e.g., epithelial cells) may express IL-8, airway macrophages appear to be a source of this chemokine, and may thus play a prominent role in early neutrophil influx into the lung.

Recent evidence suggests that the alveolar macrophage-derived cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) play important roles in granulomatous diseases. Our objective was to quantify the mRNA for these cytokines in beryllium disease, a human granulomatous disease of known etiology. We hypothesized that alveolar macrophages and bronchoalveolar lavage fluid from patients with beryllium disease and sarcoidosis would express increased levels of mRNA and proteins, respectively, for TNF-alpha, IL-1 beta, and IL-6 compared with those of normal individuals. We performed bronchoalveolar lavage and used a quantitative polymerase chain reaction to determine alveolar macrophage-derived cytokine gene expression. We determined lavage fluid cytokine levels by enzyme-linked immunosorbent assay. In patients with beryllium disease (n = 23), we observed elevated macrophage mRNA expression for TNF-alpha and IL-6 when compared with that of normal subjects (n = 7). Sarcoidosis patients (n = 6) also had increased expression for TNF-alpha and IL-6 compared with that of normal volunteers. IL-1 beta expression was similar in all three groups. In patients with beryllium disease (n = 39), lavage fluid TNF-alpha concentration was higher than that of 16 normal subjects. Lavage fluid IL-1 beta and IL-6 levels did not differ among the groups. This is the first report of macrophage cytokine expression in beryllium disease. These novel findings suggest that macrophage expression of TNF-alpha and IL-6 may be important in the human granulomatous inflammatory response.

During a 3-year period 11 neonates underwent general anesthesia for primary repair of tracheo-esophageal fistula (TEF). The age ranged from 1-10 days. Out of these patients, 8 (72.7%) had atresia of the esophagus with a blind upper pouch and lower segment communicating with a trachea. A total of 7 patients (63.6%) had aspiration pneumonitis pre-operatively. Intubation was difficult in 3 (27.3%). There was no intraoperative mortality. However, the incidence of post-operative mortality was 27.3% (3 cases). The cause of death in all these cases was severe non-resolving pneumonia.

Twenty patients were divided into 2 groups. Group - A had 10 ASA Grade I while Group - B consisted of 10 asymptomatic patients with ECG evidence of ischaemia. One week of coronary dilator treatment was given to the patients in group-B before surgery. Intra operative cardioscopic monitoring was done in both the groups. In group-B, 5 patients showed ECG evidence of intraoperative myocardial ischaemia, and/or ventricular ectopics, which were in most cases attributable to anaesthetic/surgical stimuli but were not always associated with increased Rate pressure product. In group-A only one patient showed ECG evidence of ischaemia intraoperatively. It is therefore concluded that patients with optimal therapy for IHD continue to be at risk of intraoperative cardiovascular abnormalities.

Thirty normotensive patients (ASA class I) and 30 treated hypertensives without any cardiac problem (ASA class II) were subjected to elective cholecystectomy under general anaesthesia. Patients' age ranged from 25-50 yr, and male:female ratio was 1:11. There were significant increases in heart rate and mean arterial pressure in both the groups (P less than 0.05) during surgical manipulations for removal of the diseased gall bladders. The alterations in the treated hypertensive patients were not only much more than in the normotensives, but also were associated with tachyarrhythmias in 33.33 per cent of hypertensive patients. All changes returned to the pre-induction level at the end of the surgery. Mediation through fifth thoracic spinal segment, a common source of sympathetic supply to heart and gallbladder, explained the observed cholecystocardiac link. Anaesthetists therefore need to be vigilant during cholecystectomies.

Thirty-six adult female patients undergoing abdominal hysterectomy under general anaesthesia were evaluated for the haemodynamic effects of IV verapamil in bolus dose of either 50 micrograms/kg (group A), 60 micrograms/kg (group B) or 75 micrograms/kg (group C). The result showed a dose dependent fall in the mean arterial pressure and increase in the P-R interval. The fall in heart rate was marginally more in group A and B as compared to group C.

The quality of extubation and circulatory changes during extubation of the trachea with or without prior xylocaine (1 mg/kg iv) were observed in 30 patients having CAD or 2 or more cardiac risk factors. 73.33 per cent of the patients receiving xylocaine had smooth extubation (grade I) in contrast to only 46.66 per cent in the control group. Also, in patients in the xylocaine group, the circulatory changes were statistically insignificant as compared to highly significant rise in rate pressure product in the control group.

Changes in serum potassium level in 21 control patients and 21 patients with infections of varying severity were measured after administration of succinylcholine. Serum potassium levels increased significantly in patients with infections, but not in the normal control patients. The magnitude of the increase in serum potassium was related to the severity and duration of infection.