Improving diagnostic performance of 18F-FDG-PET/CT for assessment of regional nodal involvement in non-small cell lung cancer.

AIM: To assess the diagnostic performance of combined 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) mediastinal blood pool (MBP) activity cut-off for staging nodal involvement, and to examine other variables that may improve the diagnostic performance of PET/CT in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: All patients diagnosed with NSCLC who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and 18F-FDG-PET/CT between June 2016 and August 2018 were included. Nodal station and nodal staging-based analyses were performed, comparing the MBP cut-off and five other PET/CT parameters (node maximum standardised uptake value [SUVmax], node/MBP SUVmax ratio, node/tumour SUVmax ratio, node short axis diameter, and node SUVmax/node short axis diameter ratio) with histopathology results. The optimal cut-off value for each PET/CT parameter was determined using receiver operating characteristic curve analysis. RESULTS: One hundred and thirteen patients with a total of 321 nodes with pathological sampling were included. Nodal activity above MBP on PET/CT demonstrated 97.4% sensitivity, 35.8% specificity, 32.8% positive predictive value, and 97.8% negative predictive value. Of the five other PET/CT parameters examined, the two most promising were node SUVmax and node/MBP SUVmax. The node SUVmax cut-off of 3.9 demonstrated 90.9% sensitivity and 61.9% specificity, and the node/MBP SUVmax cut-off of 1.7 demonstrated 90.9% sensitivity and 60.7% specificity. CONCLUSION: Compared to the MBP cut-off, use of a higher node/MBP SUVmax ratio cut-off and use of other PET/CT variables can improve the diagnostic performance of PET/CT for NSCLC nodal staging. In particular, specificity for detecting malignant nodal involvement is improved while maintaining high sensitivity.

Guidelines for training in cardiovascular magnetic resonance (CMR).

These "Guidelines for training in Cardiovascular Magnetic Resonance" were developed by the Certification Committee of the Society for Cardiovascular Magnetic Resonance (SCMR) and approved by the SCMR Board of Trustees.

Multilocation field trials for risk assessment of a combination fungicide Fluopicolide + Propamocarb in tomato.

Dissipation kinetics of two systemic fungicides, namely fluopicolide and propamocarb used as a combination formulation (Infinito 68.75 SC), were studied on tomato at four different locations by the All India Network Project on Pesticide Residues to recommend their pre-harvest interval (PHI) and to propose the maximum residue limits (MRL) for the two fungicides based on chronic hazard exposure assessment. The combination fungicide was sprayed thrice at the recommended dosage of 93.75 g a.i./ha fluopicolide and 937.50 g a.i./ha propamocarb as well as at double the recommended dosage of 187.50 g a.i./ha fluopicolide and 1875.0 g a.i./ha propamocarb on tomato crops and the residues were monitored periodically by GC-MS. The fungicides dissipated to below the limit of quantification (LOQ) within 10 to 15 days, with a half-life of 2-4 days for fluopicolide and 1-2 days for propamocarb. Taking into consideration the MRLs of codex and calculations made using the method of MRL fixation of the Food Safety and Standard Authority of India (FSSAI) as well as the Organization for Economic Co-operation and Development (OECD) calculator, MRL of 5 mg/kg is proposed for fluopicolide and 15 mg/kg for propamocarb, following critical exposure of the commodity considering PHI of 1 day.

Persistence and dissipation kinetics of deltamethrin on chili in different agro-climatic zones of India.

Multi-location supervised field trials were conducted at four different agro climatic locations in India to evaluate the dissipation pattern of deltamethrin on chili. Deltamethrin 10 EC was applied on chili @17.5 and 35 g a.i. ha(-1), samples of green chili were drawn at different time intervals and that of red chili and soil at harvest time and quantified by gas liquid chromatography equipped with electron capture detector. The identity of residues were confirmed by Gas Chromatograph-Mass Spectrophotometer in selective ion monitoring mode in mass range 181, 253 m/z. Limit of quantification of the method was found to be 0.01 mg kg(-1). Half-life of deltamethrin at application rate of 17.5 g a.i. ha(-1) varied from 0.36 to 1.99 days and at double the application rate was found to range from 0.38 to 2.06 days. Residues of deltamethrin were found below its determination limit of 0.01 mg kg(-1) in red chili and soil. On the basis of the data generated, Deltamethrin 10 EC has been registered for use on chili in India and its Maximum Residue Limit has been fixed as 0.05 µg/g.

Nanotechnology and pharmaceutical inhalation aerosols.

Pharmaceutical inhalation aerosols have been playing a crucial role in the health and well being of millions of people throughout the world for many years. The technology's continual advancement, the ease of use and the more desirable pulmonary-rather-than-needle delivery for systemic drugs has increased the attraction for the pharmaceutical aerosol in recent years. But administration of drugs by the pulmonary route is technically challenging because oral deposition can be high, and variations in inhalation technique can affect the quantity of drug delivered to the lungs. Recent advances in nanotechnology, particularly drug delivery field have encouraged formulation scientists to expand their reach in solving tricky problems related to drug delivery. Moreover, application of nanotechnology to aerosol science has opened up a new category of pharmaceutical aerosols (collectively known as nanoenabled-aerosols) with added advantages and effectiveness. In this review, some of the latest approaches of nano-enabled aerosol drug delivery system (including nano-suspension, trojan particles, bioadhesive nanoparticles and smart particle aerosols) that can be employed successfully to overcome problems of conventional aerosol systems have been introduced.

Stable 'arrested' non-aqueous edible foams based on food emulsifiers.

Stable oil foams with structured air-oil interfaces and high overrun (φair ≫ 0.5) were fabricated using edible emulsifiers (sucrose esters and lecithin). Advanced microscopy was used to understand the microstructure of these 'arrested' non-aqueous foams which displayed interesting rheological behaviour (yielding and thixotropy). Such complex colloids stabilized by edible ingredients could find important industrial applications in the development of novel textured food products.

Low levels of high-density lipoprotein cholesterol are associated with vascular remodeling in cardiac transplant recipients.

BACKGROUND: Early atherosclerosis may be associated with compensatory vessel enlargement, termed positive remodeling. Enlarged brachial artery diameter has been reported in patients with risk factors for atherosclerosis and in individuals with coronary atherosclerosis, indicating that brachial artery enlargement is a marker for the presence of atherosclerotic changes. Cardiac transplant recipients often have abnormal lipid levels, but the effect of specific lipid abnormalities on vascular remodeling in this population has not been evaluated. This study examined the relationship between lipid levels and brachial artery diameter in cardiac transplant recipients. METHODS: Thirty-five stable cardiac transplant recipients underwent high-resolution brachial artery ultrasound to evaluate resting brachial artery diameter. Levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were determined and the presence of other cardiac risk factors was assessed. RESULTS: Brachial artery diameter was larger (4.3 +/- 0.1 mm) in subjects with low levels of HDL-C (< 40 mg/dL, n = 11) compared to subjects with high HDL-C (> or = 40 mg/dL, n = 24), who had a mean brachial artery diameter of 3.7 +/- 0.1 mm (P = .006). Neither high LDL-C (> or = 100 mg/dL) nor high triglycerides (> or = 200 mg/dL) were associated with differences in brachial artery diameter. Multivariate analysis demonstrated that the relationship between low HDL-C and increased brachial artery diameter was independent of body surface area or statin use. CONCLUSIONS: Low levels of HDL-C are an independent predictor of brachial artery enlargement in stable cardiac transplant recipients. These findings suggest that suboptimal HDL-C levels may be associated with the development of vascular remodeling and atherosclerosis in this population.

Noninvasive testing for coronary artery disease in women.

Coronary artery disease is a major cause of morbidity and mortality for women in North America and Europe. Given the significance of coronary disease as a public health problem among women, accurate diagnosis of this condition is of great importance. Several noninvasive testing modalities are available for the diagnosis of coronary heart disease. An understanding of gender-based differences related to noninvasive cardiac testing is useful in order to optimally utilize these tests and improve detection and clinical outcomes in women.

Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease.

OBJECTIVES: We studied whether assessment of endothelium-dependent vasomotion (EDV) with brachial artery ultrasound (BAUS) imaging predicts the presence or absence of coronary artery disease (CAD) as defined by exercise myocardial perfusion imaging (ExMPI). BACKGROUND: Abnormalities in EDV can be detected in arteries before the development of overt atherosclerosis, and its presence may predict poor long-term prognosis. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral EDV. METHODS: Clinically-indicated ExMPI along with BAUS were performed in 94 subjects (43 women, 51 men). Coronary artery disease was defined by myocardial ischemia or infarction on single photon emission computed tomography images. Flow-mediated dilation (FMD) after upper arm occlusion was defined as the percent change in arterial diameter during reactive hyperemia relative to the baseline. RESULTS: Subjects with CAD by ExMPI (n = 23) had a lower FMD (6.3 +/- 0.7%) than those without CAD by ExMPI (n = 71) (10.5 +/- 0.6%; p = 0.0004). Flow-mediated dilation was highly predictive for CAD with an odds ratio of 1.32 for each percent decrease in FMD (p = 0.001). Based on a receiver-operator analysis, an FMD of 10% was used as a cut-point for further analysis. Twenty-one of 23 subjects who were positive for ExMPI had an FMD < 10% (sensitivity 91%), whereas only two of 40 subjects with an FMD > or =10% were ExMPI-positive (negative predictive value: 95%). There was a correlation between the number of cardiac risk factors and FMD. Individuals with an FMD < 10% exercised for a shorter duration than those with an FMD > or =10% (456 +/- 24 vs. 544 +/- 31 s, respectively; p = 0.02). CONCLUSIONS: Assessment of EDV with BAUS has a high sensitivity and an excellent negative predictive value for CAD and, thus, has the potential for use as a screening tool to exclude CAD in low-risk subjects. Further standardization of BAUS is required, however, before specific cut-points for excluding CAD can be established.

Heart failure etiology affects peripheral vascular endothelial function after cardiac transplantation.

OBJECTIVES: The goal of this study was to examine the effect of heart failure etiology on peripheral vascular endothelial function in cardiac transplant recipients. BACKGROUND: Peripheral vascular endothelial dysfunction occurs in patients with heart failure of either ischemic or nonischemic etiology. The effect of heart failure etiology on peripheral endothelial function after cardiac transplantation is unknown. METHODS: Using brachial artery ultrasound, endothelium-dependent, flow-mediated dilation (FMD) was assessed in patients with heart failure with either nonischemic cardiomyopathy (n = 10) or ischemic cardiomyopathy (n = 7), cardiac transplant recipients with prior nonischemic cardiomyopathy (n = 10) or prior ischemic cardiomyopathy (n = 10) and normal controls (n = 10). RESULTS: Patients with heart failure with either ischemic cardiomyopathy or nonischemic cardiomyopathy had impaired FMD (3.6 +/- 1.0% and 5.1 +/- 1.2%, respectively, p = NS) compared with normal subjects (13.9 +/- 1.3%, p < 0.01 compared with either heart failure group). In transplant recipients with antecedent nonischemic cardiomyopathy, FMD was markedly higher than that of heart failure patients with nonischemic cardiomyopathy (13.0 +/- 2.4%, p < 0.001) and similar to that of normal subjects (p = NS). However, FMD remained impaired in transplant recipients with prior ischemic cardiomyopathy (5.5 +/- 1.5%, p = 0.001 compared with normal, p = 0.002 vs. transplant recipients with previous nonischemic cardiomyopathy). CONCLUSIONS: Peripheral vascular endothelial function is normal in cardiac transplant recipients with antecedent nonischemic cardiomyopathy, but remains impaired in those with prior ischemic cardiomyopathy. In contrast, endothelial function is uniformly abnormal for patients with heart failure, regardless of etiology. These findings indicate that cardiac transplantation corrects peripheral endothelial function for patients without ischemic heart disease, but not in those with prior atherosclerotic coronary disease.

Iron deficiency and sickle cell anemia.

In a patient with sickle cell anemia, iron deficiency was accompanied by hypochromic, microcytic RBCs, absence of bone marrow iron, and a low serum ferritin level. The mean corpuscular hemoglobin concentration (MCHC) was decreased (27.6 g/dL) and was associated with an extreme scarcity of sickled erythrocytes in blood smears. Iron therapy resulted in reticulocytosis and an increase in sickled erythrocytes. In vitro studies demonstrated a decrease in sickling of erythrocytes as a function of oxygen saturation of the blood when the patient was iron deficient. The whole blood oxygen dissociation curve showed a substantial decrease in oxygen pressure necessary to produce 50% saturation of hemoglobin at pH 7.4 and 37 degrees C (P50), indicating an increased oxygen affinity. These data suggest that a reduction of the MCHC induced by iron deficiency may ameliorate sickling.

Pulmonary edema associated with subarachnoid hemorrhage. Evidence for a cardiogenic origin.

A 56-year-old woman with no history of cardiac disease developed acute pulmonary edema following a subarachnoid hemorrhage. A constellation of findings, including elevated creatine kinase MB isoenzyme activity in the absence of electrocardiographic or scintigraphic evidence of acute myocardial infarction, elevated pulmonary artery wedge pressure, segmental wall motion abnormalities, and depressed ejection fraction of the left ventricle demonstrated by two-dimensional echocardiography and radionuclear ventriculography, pointed to a direct myocardial injury leading to cardiac failure. The evidence for cardiogenic origin of pulmonary edema provided by this case is in contrast to the belief that "neurogenic" pulmonary edema is of noncardiac origin.

Association of histone acetylation at the ACTA2 promoter region with epithelial mesenchymal transition of lens epithelial cells.

PURPOSE: Epithelial mesenchymal transition (EMT) plays a central role in the development of fibrotic complications of the lens. The current study is designed to check whether EMT of lens epithelial cells (LECs) is regulated by epigenetic modifications and to evaluate the effect of Trichostatin-A (TSA) on the transforming growth factor-ß (TGF-ß)-induced EMT. METHODS: Fetal human LECs (FHL124) were treated with TGF-ß2 in the presence or absence of TSA. Levels of mRNA, protein, as well as localization of α-smooth muscle actin (αSMA) were studied along with migration of LECs. Acetylation of histone H4 was analyzed and chromatin immunoprecipitation (ChIP) was carried out to study the level of acetylated histone H4 at the promoter of αSMA gene (ACTA2). Student's t-test was used for statistical analysis. RESULTS: TGF-ß2 treatment resulted in myofibroblast-like changes and increased migratory capacity of FHL124. Protein and mRNA expression of αSMA increased, and immunofluorescence revealed presence of extensive stress fibers. TSA treatment preserved epithelial morphology, retarded cell migration, and abrogated an increase in αSMA levels. TSA led to the accumulation of acetylated histone H4 that was reduced on TGF-ß2 treatment. However, increased level of histone H4 acetylation was found at the ACTA2 promoter region during TGF-ß treatment. CONCLUSIONS: The increased level of αSMA, a hallmark of EMT in LECs, is associated with increased level of histone H4 acetylation at its promoter region, and TSA helps in suppressing EMT by epigenetically reducing this level. TSA thus shows promising potential in management of fibrotic conditions of the lens.

Acute Na+,K+-ATPase inhibition with bufalin impairs pressure natriuresis in the rat.

Although it has been reported that Na+,K+-ATPase inhibition with bufalin induces acute and chronic hypertension in the rat, the mechanisms mediating this response are unclear. To examine the role of the kidney in this process, glomerular filtration rate, renal blood flow, and pressure natriuresis were determined in rats treated with bufalin or vehicle during changes in renal perfusion pressure. Mean arterial pressure increased from 123 +/- 4 to 149 +/- 3 mm Hg (P < .05) after 40 minutes of intravenous bufalin and remained at this level. In control rats, glomerular filtration rate was well autoregulated. In bufalin-treated rats, glomerular filtration rate fell with decreasing renal perfusion pressure. Glomerular filtration rate autoregulatory index was greater in bufalin-treated than control rats (P < .05). Renal blood flow showed a similar pattern. Urine flow and sodium excretion were less in bufalin-treated than control rats at equivalent renal perfusion pressures. The slope of the line describing the relation between urine flow and renal perfusion pressure was greater (P < .05) in control than bufalin-treated rats. Similarly, the slope of the line relating sodium excretion to renal perfusion pressure was greater (P < .05) in control than bufalin-treated rats. Thus, acute increases in blood pressure during Na+, K+-ATPase inhibition are associated with impaired renal autoregulation and pressure natriuresis. This effect may be important in chronic hypertension associated with Na+,K+-ATPase inhibition in the rat.

Pressure natriuresis after adrenomedullin in anesthetized spontaneously hypertensive rats.

Adrenomedullin (ADM), a peptide with potent vasodilatory and natriuretic actions, is elevated in patients with essential hypertension. Because pharmacological doses of ADM result in renal vasodilation and natriuresis, it has been suggested that ADM may play a modulatory role in hypertension through potential actions on renal pressure natriuresis. However, it is unclear whether elevation of plasma ADM within the pathophysiological range has similar actions. To determine the effects of pathophysiological doses of ADM on blood pressure and on the relationship between renal perfusion pressure (RPP) and renal hemodynamics and sodium excretion, renal function was determined at RPPs of 80, 105, 130, and 155 mm Hg in spontaneously hypertensive rats (SHR) infused with ADM at 50 ng x kg(-1) x min(-1) (ADM-50, n=5) and at 100 ng x kg(-1) x min(-1) (ADM-100, n=5) and in control SHR (n=5). Decreasing RPP from 155 to 80 mm Hg in control SHR decreased (P<.05) absolute sodium excretion from 0.81+/-0.25 to 0.04+/-0.02 microEq/min, fractional sodium excretion from 0.32+/-0.11% to 0.06+/-0.04%, and urine flow rate from 11.5+/-2.8 to 1.03+/-0.31 microL/min. ADM infusion elevated (P<.05) plasma ADM levels in ADM-infused SHR (679+/-47 pg/mL in ADM-50, 858+/-79 in ADM-100) compared with control (79.5+/-27.8). However, although reduction of RPP from 155 to 80 mm Hg in ADM rats decreased absolute sodium excretion (ADM-50, 0.98+/-0.10 to 0.09+/-0.04 microEq/min; ADM-100, 0.95+/-0.09 to 0.07+/-0.02 microEq/min), fractional sodium excretion (ADM-50, 0.31+/-0.03% to 0.17+/-0.04%; ADM-100, 0.33+/-0.02% to 0.09+/-0.01%), and urine flow (ADM-50, 13.6+/-1.4 to 1.73+/-0.75 microL/min; ADM-100, 13.5+/-1.5 to 1.07+/-0.16 microL/min), these decreases were not different from values found in controls. Renal plasma flow and glomerular filtration rate were also similar in control and ADM-treated SHR at each level of RPP. Thus, acute increases in ADM to levels found in pathophysiological conditions have no effect on blood pressure, pressure natriuresis, or renal autoregulation in the SHR. These findings do not support the hypothesis that ADM serves as a modulating factor in hypertension, at least in the SHR.

Echocardiographic analysis of regional and global left ventricular shape in Chagas' cardiomyopathy.

Chagas' heart disease is a common form of cardiomyopathy in Latin America and an important cause of cardiac morbidity and mortality there. Left ventricular (LV) apical aneurysm and LV dysfunction are frequent findings in Chagas' cardiomyopathy. Because cardiac shape has important implications for LV function, we sought to characterize regional and global changes in LV geometry in Chagas' heart disease. Quantitative shape analysis was performed on 2-dimensional echocardiograms from 43 patients with Chagas' cardiomyopathy. Regional shape was quantitated by measuring endocardial curvature and global shape was evaluated by Fourier shape analysis of the endocardial contour. Data from 22 age- and sex-matched normal test subjects were used for comparison. Regional shape analysis demonstrated decreased apical curvature (consistent with blunting of normal apical shape) in the group with Chagas' disease compared with controls (apical 2-chamber view: 19 +/- 1 vs 24 +/- 1 [p = 0.0039] at end-diastole and 20 +/- 2 vs 29 +/- 3 [p = 0.0019] at end-systole). Fourier shape power index was decreased in the Chagas' group, consistent with a more spherical ventricle (apical 2-chamber view: 9 +/- 1 vs 17 +/- 2 [p <0.0001] at end-diastole and 12 +/- 1 vs 35 +/- 3 [p <0.0001] at end-systole). Shape changes among the population with Chagas' disease were further evaluated in those with end-diastolic volumes equal to or greater than the median for the group (104 ml) and those < 104 ml. Global shape did not differ between patients with dilated ventricles and those with relatively nondilated ventricles. Diastolic Fourier shape power index = 8 +/- 2 in dilated ventricles compared with 9 +/- 5 in nondilated ventricles (p = 0.53); systolic Fourier shape power index = 10 +/- 2 in dilated versus 14 +/- 2 in nondilated ventricles (p = 0.15) (apical 2-chamber view). In Chagas' cardiomyopathy, LV apical deformation results in disruption of the optimal global prolate-ellipsoid shape, even in patients with relatively preserved LV volumes.

Right ventricular dilation in primary amyloidosis: an independent predictor of survival.

This study was designed to characterize the geometry and function of the right ventricle and its prognostic significance in patients with primary (AL) cardiac amyloidosis. AL amyloidosis is an infiltrative systemic disease that can result in thickening of heart structures and rapidly progressive congestive heart failure due to restrictive ventricular physiology and eventual systolic dysfunction. Thirty-seven patients with AL amyloid heart involvement and 20 normal control subjects were evaluated using 2-dimensional and Doppler echocardiography. Based on the ratio of left-to-right end-diastolic ventricular chamber areas, patients were classified into 2 groups: 25 patients with disproportionate right ventricular (RV) dilation (left ventricular to RV ratio < or = 2) and 12 with a ventricular area ratio > 2. Patients with a relatively dilated right ventricle (ratio < or = 2) had a shorter median survival (4 months) compared with patients with an area ratio > 2 (10 months, p <0.003). Of multiple clinical, echocardiographic, and Doppler features entered into a multifactorial model, a ventricular area ratio < or = 2 remained the only independent predictor of survival. Patients with AL amyloid heart disease represent a heterogeneous population with regard to both prognosis and the relative degree of right to left ventricular dilation. RV dilation in patients with amyloid heart disease appears to be associated with more severe involvement and is associated with a very poor prognosis with a median survival of only 4 months.

Serum ferritin and sequestered stores of body iron.

A 47-year-old man with sickle cell anemia, chronic cor pulmonale, and congestive heart failure died following a short illness. A diagnosis of iron deficiency was established during life by usually accepted criteria including a low serum ferritin concentration. Autopsy showed no stainable iron in the bone marrow, liver, and the heart. Marked deposits of iron were seen in the kidneys and the atrophic spleen. These findings suggest that the serum ferritin concentration may not reflect the metabolically sequestered stores of iron in the spleen and the kidneys.

The use of frozen, thawed erythrocytes in blood banking: a report of 28 months' experience in a large transfusion service.

A program of component therapy using largely frozen erythrocytes was initiated at Cook County Hospital in July 1973. Use of the three existing washing systems for routine preparation of frozen erythrocytes has shown that there are differences in the levels of free hemoglobin, hematocrit, and residual glycerol in the washed products. Adenosine triphosphate, 2,3-diphosphoglycerate, and extracellular potassium and sodium were found to be within acceptable limits. Some expired units were cultured and were found to be positive for Staphylococcus and Corynebacterium. The source of contamination has not been determined. Frozen blood, when available, has been given to all patients, regardless of age or clinical condition. The incidence of transfusion reactions has decreased from 0.57% prior to the inception of the component therapy program to 0.11% since that time. Two cases of possible posttransfusion hepatitis occurred in patients who had received non-frozen blood, and in three patients who received non-frozen erythrocytes and/or components as well as frozen blood. Although the goal of the program was the use of frozen erythrocytes exclusively, only 64% use was achieved, as sufficient quantities of blood for freezing were not available at all times.