The current status and future of FDA-approved artificial intelligence tools in chest radiology in the United States.

Artificial intelligence (AI) is becoming more widespread within radiology. Capabilities that AI algorithms currently provide include detection, segmentation, classification, and quantification of pathological findings. Artificial intelligence software have created challenges for the traditional United States Food and Drug Administration (FDA) approval process for medical devices given their abilities to evolve over time with incremental data input. Currently, there are 190 FDA-approved radiology AI-based software devices, 42 of which pertain specifically to thoracic radiology. The majority of these algorithms are approved for the detection and/or analysis of pulmonary nodules, for monitoring placement of endotracheal tubes and indwelling catheters, for detection of emergent findings, and for assessment of pulmonary parenchyma; however, as technology evolves, there are many other potential applications that can be explored. For example, evaluation of non-idiopathic pulmonary fibrosis interstitial lung diseases, synthesis of imaging, clinical and/or laboratory data to yield comprehensive diagnoses, and survival or prognosis prediction of certain pathologies. With increasing physician and developer engagement, transparency and frequent communication between developers and regulatory agencies, such as the FDA, AI medical devices will be able to provide a critical supplement to patient management and ultimately enhance physicians' ability to improve patient care.

Prospective machine learning CT quantitative evaluation of idiopathic pulmonary fibrosis in patients undergoing anti-fibrotic treatment using low- and ultra-low-dose CT.

AIM: To compare the machine learning computed tomography (CT) quantification tool, Computer-Aided Lung Informatics for Pathology Evaluation and Ratings (CALIPER) to pulmonary function testing (PFT) in assessing idiopathic pulmonary fibrosis (IPF) for patients undergoing treatment and determine the effects of limited (LD) and ultra-low dose (ULD) CT on CALIPER performance. MATERIALS AND METHODS: Thirty-eight IPF patients underwent PFT and standard, LD, and ULD CT. CALIPER classified each CT voxel into either vessel-related structures (VRS), normal, reticular (R), honeycomb (HC) or ground-glass (GG) features. CALIPER-derived interstitial lung disease (ILD) extent represented the sum of GG, R and HC values. Repeated-measures correlation coefficient (ρrm) and 95% confidence interval (CI) evaluated CALIPER features correlation with PFT. Lin's concordance correlation coefficient (CCC) assessed concordance of CALIPER parameters across different CT dosages. RESULTS: Twenty patients completed 12 months of follow-up. CALIPER ILD correlated significantly with percent predicted (%) forced vital capacity (FVC) and forced expiratory volume in 1 second (%FEV1; p=0.004, ρrm -0.343, 95% CI [-0.547, -0.108] and 0.008, -0.321, [-0.518, -0.07], respectively). VRS significantly correlated with %FVC and %FEV1 (p=0.000, ρrm -0.491, 95% CI [-0.685, -0.251] and -0.478, 0.000, [-0.653, -0.231], respectively). There was near perfect LD and moderate ULD concordance with standard dose CT for both ILD (CCC 0.995, 95% CI 0.988-0.999 and 0.9, 0.795-0.983, respectively) and VRS (CCC 0.989, 95% CI 0.963-0.997 and 0.915, 0.806-0.956, respectively). CONCLUSIONS: CALIPER parameters correlate well with PFTs for evaluation of IPF in patients undergoing anti-fibrotic treatment without being influenced by dose variation. CALIPER may serve as a robust, objective adjunct to PFTs in assessing anti-fibrotic treatment related changes.

Comparison between the effects of deep and moderate neuromuscular blockade during transurethral resection of bladder tumor on endoscopic surgical condition and recovery profile: a prospective, randomized, and controlled trial.

PURPOSE: To compare between deep neuromuscular blockade (NMB) and moderate NMB with respect to endoscopic surgical conditions and recovery profiles in patients with general anesthesia for transurethral resection of bladder (TURB). METHODS: 108 patients undergoing elective TURB were randomized into two groups: the moderate NMB (n = 54) or deep NMB (n = 54) group. After the operation, NMB was reversed with 2 mg/kg sugammadex at a train-of-four (TOF) count of 1 or 2 (moderate NMB group) or with 4 mg/kg sugammadex at post-tetanic count (PTC) of 2 (deep NMB group). Surgeons, who were blinded to the study design, rated the endoscopic surgical condition on a 5-point scale (1 = extremely poor, 2 = poor, 3 = acceptable, 4 = good, 5 = optimal) immediately following the operation. Recovery profiles, including postoperative residual curarization (PORC), respiratory complication, and recovery time, were recorded. RESULTS: No difference was observed between the two groups regarding patients and anesthesia characteristics. There were statistically significant differences in endoscopic surgical conditions between the two groups (P < 0.001). Thirty-eight patients in the deep NMB group (74%) showed optimal surgical conditions, whereas 16 patients in the moderate NMB group (30%) showed optimal endoscopic surgical conditions. No PORC and respiratory complications occurred in both groups, and no difference was found between the two groups in terms of recovery profiles, including recovery time and other adverse events. CONCLUSIONS: Deep NMB and reversal with sugammadex improved the endoscopic surgical condition without complications compared with moderate NMB and reversal with sugammadex in patients undergoing TURB.

Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial.

Background: Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone. Methods: Patients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml-1 remifentanil with 0.05 µg kg-1 h-1 naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml-1 remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery. Results: The pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22-3.84) vs 3.84 (3.76-4.00) vs 3.80 (3.69-4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups. Conclusions: The intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain. Clinical trial registration: NCT02856087.

Performance of the Minto model for the target-controlled infusion of remifentanil during cardiopulmonary bypass.

We studied the predictive performance of the Minto pharmacokinetic model during cardiopulmonary bypass in patients undergoing cardiac surgery. Patients received remifentanil target-controlled infusion using the Minto model during total intravenous anaesthesia with propofol. From 56 patients, 275 arterial blood samples were drawn before, during and after bypass to determine the plasma concentration of remifentanil, and the predicted concentrations were recorded at each time. For pooled data, the median prediction error and median absolute prediction error were 21.3% and 21.8%, respectively, and 22.1% and 22.3% during bypass. Both were 148.4% during hypothermic circulatory arrest and measured concentrations were more than three times greater than predicted (26.9 (17.0) vs. 7.1 (1.6) ng.ml-1 ). The Minto model showed considerable bias but overall acceptable precision during bypass. The target concentration of remifentanil should be reduced when using the Minto model during hypothermic circulatory arrest.

Effect of early vs. late tracheostomy on clinical outcomes in critically ill pediatric patients.

BACKGROUND: Few studies investigated the optimal timing for tracheostomy and its influence on the clinical outcomes in critically ill pediatric patients. This study evaluated the differences in clinical outcomes between early and late tracheostomy in pediatric intensive care unit (ICU) patients. METHODS: We assessed 111 pediatric patients. Patients who underwent a tracheostomy within 14 days of mechanical ventilation (MV) were assigned to the early tracheostomy group, whereas those who underwent tracheostomy after 14 days of MV were included in the late tracheostomy group. Clinical outcomes, including mortality, duration of MV, length of ICU and hospital stays, and incidence of ventilator-associated pneumonia (VAP) were compared between the groups. RESULTS: Of the 111 pediatric patients, 61 and 50 were included in the early and late tracheostomy groups, respectively. Total MV duration and the length of ICU and hospital stay were significantly longer in the late tracheostomy group than in the early tracheostomy group (all P < 0.01). The VAP rate per 1000 ventilator days before tracheostomy was 2.6 and 3.8 in the early and late tracheostomy groups, respectively. There were no significant differences in mortality rate between the groups. No severe complications were associated with tracheostomy itself. CONCLUSIONS: Tracheostomy performed within 14 days after the initiation of MV was associated with reduced duration of MV and length of ICU and hospital stay. Although there was no effect on mortality rate, children may benefit from early tracheostomy without severe complications.

SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1.

BACKGROUND: We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown. METHODS: A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer. RESULTS: Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53. CONCLUSION: Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity.

Optimal water supply reservoir operation by leveraging the meta-heuristic Harris Hawks algorithms and opposite based learning technique.

To ease water scarcity, dynamic programming, stochastic dynamic programming, and heuristic algorithms have been applied to solve problem matters related to water resources. Development, operation, and management are vital in a reservoir operating policy, especially when the reservoir serves a complex objective. In this study, an attempt via metaheuristic algorithms, namely the Harris Hawks Optimisation (HHO) Algorithm and the Opposite Based Learning of HHO (OBL-HHO) are made to minimise the water deficit as well as mitigate floods at downstream of the Klang Gate Dam (KGD). Due to trade-offs between water supply and flood management, the HHO and OBL-HHO models have configurable thresholds to optimise the KGD reservoir operation. To determine the efficacy of the HHO and OBL-HHO in reservoir optimisation, reliability, vulnerability, and resilience are risk measures evaluated. If inflow categories are omitted, the OBL-HHO meets 71.49% of demand compared to 54.83% for the standalone HHO. The HHO proved superior to OBL-HHO in satisfying demand during medium inflows, achieving 38.60% compared to 20.61%, even though the HHO may have experienced water loss at the end of the storage level. The HHO is still a promising method, as proven by its reliability and resilience indices compared to other published heuristic algorithms: at 62.50% and 1.56, respectively. The Artificial Bee Colony (ABC) outcomes satisfied demand at 61.36%, 59.47% with the Particle Swarm Optimisation (PSO), 55.68% with the real-coded Genetic Algorithm (GA), and 23.5 percent with the binary GA. For resilience, the ABC scored 0.16, PSO scored 0.15, and real coded GA scored 0.14 whilst the binary-GA has the worst failure recovery algorithm with 0.09.

Using the lactate-to-albumin ratio to predict mortality in patients with sepsis or septic shock: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate whether the lactate-to-albumin ratio (LAR) can predict mortality in patients with sepsis or septic shock. PATIENTS AND METHODS: A systematic search of the PubMed, EMBASE, Web of Science, and Google Scholar databases was conducted on December 16, 2021, for relevant articles that provided the predictive performance of LAR for mortality in patients with sepsis or septic shock. RESULTS: Eight studies encompassing a total of 4,723 patients were included in this paper. The pooled sensitivity, specificity, and diagnostic odds ratio of the LAR for predicting mortality were 0.71 (95% confidence interval [CI]: 0.54-0.84), 0.68 (95% CI: 0.58-0.76) and 5.23 (95% CI: 2.62-10.45), respectively. The area under the summary receiver operating characteristic curve was 0.74 (95% CI: 0.70-0.78). CONCLUSIONS: The current evidence suggests that LAR is moderately predictive of mortality among patients with sepsis or septic shock and may be beneficial to identify high-risk patients.

Point-of-care testing for the detection of SARS-CoV-2: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of the Food and Drug Administration Emergency Use Authorization (FDA-EUA) authorized point-of-care tests (POCTs) for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MATERIALS AND METHODS: A systematic literature search was conducted using the PubMed, Embase, and Web of Science databases for articles published till August 10, 2020. We included studies providing information regarding diagnostic test accuracy of FDA-EUA POCTs for SARS-CoV-2 detection. The methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The review protocol is registered in the International Prospective Register of Systematic Reviews (protocol number CRD42020202248). RESULTS: We included 26 studies describing a total of 3242 samples. The summary sensitivity and specificity were 0.94 [95% confidence interval (CI): 0.88-0.97] and 1.00 (95% CI: 0.99-1.00), respectively. The area under the summary receiver operating characteristic curve was 1.00 (95% CI: 0.99-1.00). A pooled analysis based on the index test revealed a summary sensitivity and specificity of Cepheid Xpert Xpress SARS-CoV-2 [0.99 (95% CI: 0.97-1.00) and 0.99 (95% CI: 0.94-1.00, respectively)] and ID NOW COVID-19 [0.78 (95% CI: 0.74-0.82) and 1.00 (95% CI: 0.98-1.00), respectively]. CONCLUSIONS: FDA-EUA POCTs, especially molecular assays, have high sensitivity, specificity, and overall diagnostic accuracy for detecting SARS-CoV-2. If approved, FDA-EUA POCTs can provide a rapid and practical way to identify infected individuals early on and help to limit the strain on the healthcare system. However, more high-quality clinical data are required to support our results.

Neutrophil-to-lymphocyte ratio for the diagnosis of pediatric acute appendicitis: a systematic review and meta-analysis.

OBJECTIVE: Acute appendicitis (AA) is one of the most common surgical emergencies and causes of acute abdominal pain in the pediatric population. However, it can be difficult to diagnose in children. We aimed to provide updated evidence on the diagnostic utility of the neutrophil-to-lymphocyte ratio (NLR) for AA, along with other conventional biomarkers, in pediatric patients. MATERIALS AND METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for eligible articles published up to May 16, 2021. RESULTS: We included 19 studies comprising a total of 5,974 pediatric cases. The overall sensitivity and specificity of the NLR were 0.82 (95% confidence interval [CI]: 0.79-0.85) and 0.76 (95% CI: 0.69-0.81), respectively. The overall diagnostic odds ratio was 14.34 (95% CI: 9.05-22.73). The area under the summary receiver operating characteristic curve was 0.86 (95% CI: 0.83-0.89). The pooled sensitivity and specificity of other biomarkers were as follows: 0.79 (95% CI: 0.71-0.86) and 0.66 (95% CI: 0.54-0.77) for the white blood cell count, 0.73 (95% CI: 0.69-0.77) and 0.68 (95% CI: 0.55-0.79) for the C-reactive protein level, 0.75 (95% CI: 0.65-0.82) and 0.78 (95% CI: 0.72-0.83) for the absolute neutrophil count, and 0.83 (95% CI: 0.79-0.87) and 0.68 (95% CI: 0.53-0.80) for the neutrophil percentage, respectively. CONCLUSIONS: The NLR has moderate predictive power for AA and can be used as a simple, auxiliary tool for diagnosis. NLR can also help clinicians decide whether to perform imaging testing when the clinical symptoms or physical examination findings are vague.

Reduction of Radiation Dose and Scanning Time While Preserving Diagnostic Yield: A Comparison of Battery-Powered and Manual Bone Biopsy Systems.

BACKGROUND AND PURPOSE: There is scarcity of data on the comparative efficacy between bone biopsy drill systems across various types of bone lesions. Our aim was to investigate differences in diagnostic yield, scanning time, and radiation dose between manual and battery-powered bone biopsy systems in CT-guided biopsies of lytic, sclerotic, and infectious bone lesions. MATERIALS AND METHODS: This was a retrospective single-center institutional review board-approved study. A total of 585 CT-guided core needle biopsies were performed at 1 institution from May 2010 to February 2019. Classification of bone lesions, location, bone biopsy system, suspected origin of primary disease, final pathologic diagnosis, diagnostic yield, presence of crush artifacts, radiation dose, and scanning times were collected. For the battery-powered system, OnControl was used. For the manual drill system, Bonopty, Osteo-site, and Laurane drill systems were used. Comparisons in lytic and sclerotic lesions and suspected discitis/osteomyelitis were made using the Fisher exact test. Subgroup analysis of the drill systems for scanning time and radiation dose was performed by 1-way ANOVA. RESULTS: Our patient cohorts consisted of a total of 585 patients with 422 lytic, 110 sclerotic, and 53 suspected infectious lesions. The mean age was 62 ± 13 years with a male/female ratio of 305:280 for all lesions. The diagnostic yield was 85.5% (362/422) for lytic, 82.7% (91/110) for sclerotic, 50.9% (27/53) for infectious lesions, and 82.1% (480/585) for all lesions. No statistical difference was found when comparing diagnostic yields of powered drills with the manual systems for lytic, sclerotic, and infectious lesions. However, in a subgroup analysis, radiation dose and scanning time were significantly lower for powered drill compared with manual drill systems in lytic (P = .001 for both) and sclerotic lesions (P = .028 and P = .012, respectively). No significant differences were seen between the drill systems for suspected infectious lesions. CONCLUSIONS: Our findings demonstrate that there was no statistically significant difference in diagnostic yield when comparing battery-powered and manual bone biopsy systems for CT-guided bone biopsies; however, the use of the power drill system resulted in significantly reduced scanning time and radiation dose in lytic and sclerotic lesions.

Combination of Imaging Features and Clinical Biomarkers Predicts Positive Pathology and Microbiology Findings Suggestive of Spondylodiscitis in Patients Undergoing Image-Guided Percutaneous Biopsy.

BACKGROUND AND PURPOSE: Pathology and microbiology results for suspected spondylodiscitis on MR imaging are often negative in up to 70% of cases. We aimed to predict whether MR imaging features will add diagnostic value when combined with clinical biomarkers to predict positive findings of spondylodiscitis on pathology and/or microbiology from percutaneous biopsy. MATERIALS AND METHODS: In this retrospective single-center institutional review board-approved study, patients with radiologically suspected spondylodiscitis and having undergone percutaneous biopsies were assessed. Demographic characteristics, laboratory values, and tissue and blood cultures were collected. Pathology and microbiology results were used as end points. Three independent observers provided MR imaging-based scoring for typical MR imaging features for spondylodiscitis. Multivariate logistic regression and receiver operating characteristic analysis were performed to determine an optimal combination of imaging and clinical biomarkers in predicting positive findings on pathology and/or microbiology from percutaneous biopsy suggestive of spondylodiscitis. RESULTS: Our patient cohort consisted of 72 patients, of whom 33.3% (24/72) had spondylodiscitis. The mean age was 63 ± 16 years with a male/female ratio of 41:31. Logistic regression revealed a combination with an area under the curve of 0.72 for pathology and 0.68 for pathology and/or microbiology. Epidural enhancement on MR imaging improved predictive performance to 0.87 for pathology and 0.78 for pathology and/or microbiology. CONCLUSIONS: Our findings demonstrate that epidural enhancement on MR imaging added diagnostic value when combined with clinical biomarkers to help predict which patients undergoing percutaneous biopsy will have positive findings for spondylodiscitis on pathology and/or microbiology.

Guanine nucleotides modulate the binding affinity of the oligopeptide chemoattractant receptor on human polymorphonuclear leukocytes.

The oligopeptide chemoattractant receptor on human polymorphonuclear leukocyte (PMN) membranes exists in two affinity states. Since guanine nucleotides regulate the binding affinity and transductional activity of several other types of receptors, we examined the effect of nucleotides on the binding of N-formyl-methionyl peptides to their receptors on human PMN membranes. The addition of guanylylimidodiphosphate (0.1 mM), a nonhydrolyzable derivative of guanosine triphosphate (GTP), to PMN membrane preparations reduced the fraction of high-affinity receptors detected in equilibrium binding studies from 21.3 +/- 0.13 to 11.8 +/- 0.05% (P less than 0.03), without altering the binding affinities. Since the total number of receptors remained unchanged, the effect of guanylylimidodiphosphate was to convert a portion of the receptors from the high-affinity state to the low-affinity state. At the maximal concentration of guanine nucleotide tested, approximately 50% of the high-affinity sites were converted to low-affinity sites. The findings obtained by equilibrium binding were supported by kinetic studies since the dissociation of the radiolabeled oligopeptide chemoattractant N-formyl-methionyl-leucyl-[3H]phenylalanine from PMN membranes was accelerated in the presence of guanine nucleotide. The effect of guanine nucleotides was reversed upon washing, indicating that affinity conversion is bidirectional. The guanine nucleotide effects were greatest with nonhydrolyzable derivatives of GTP followed by GTP then guanosine diphosphate. Neither guanosine monophosphate nor any adenine nucleotide tested had an effect on receptor binding. These data suggest a role for guanine nucleotides in the regulation of stimulus-receptor coupling of chemoattractant receptors on human PMN.

Stimulation by leukotriene D4 of increases in the cytosolic concentration of calcium in dimethylsulfoxide-differentiated HL-60 cells.

The C6-sulfidopeptide leukotrienes C4 (LTC4) and D4 (LTD4) evoked increases in the cytosolic concentration of intracellular calcium ([Ca+2]i) in dimethylsulfoxide-differentiated HL-60 cells, as assessed by the fluorescence of quin-2. The increases in [Ca+2]i reached a peak within 15-90 s, attained 50% of the maximum level at 1.2 nM LTD4 and 60 nM LTC4, were greater in maximal magnitude for LTD4 than LTC4, and subsided in 5-7 min. Flow cytometric evaluation of the LTD4-induced increases in [Ca+2]i, reflected in increases in the fluorescence of intracellular indo-1, revealed that a mean of 77% of differentiated HL-60 cells responded, as contrasted with lesser increases in only 50% of undifferentiated HL-60 cells. The capacity of pretreatment of HL-60 cells with LTD4 to prevent subsequent responses of [Ca+2]i to LTC4 and LTD4, and the finding that the serine-borate inhibitor of conversion of LTC4 to LTD4 suppressed concurrently both LTC4-induced rises in [Ca+2]i and increases in adherence to Sephadex G-25 indicated that the responses of HL-60 cells to LTC4 required conversion to LTD4. That pertussis toxin and a chemical antagonist of LTD4 reduced the [Ca+2]i response suggested a dependence on LTD4 receptors. The LTD4-induced increases in [Ca+2]i were dependent on extracellular calcium and diminished by lanthanum, but not affected by nifedipine nor associated with changes in membrane potential, as measured with the fluorescent probe 3,3'-dipentyloxacarbocyanine. Thus, the increase in [Ca+2]i in HL-60 cells, which is coupled to an increase in adherence, appears to involve LTD4 receptor-specific and voltage-independent calcium channels in the plasma membrane.

Uptake of cholesterol-rich remnant lipoproteins by human monocyte-derived macrophages is mediated by low density lipoprotein receptors.

The uptake and degradation of cholesterol-rich remnant lipoproteins, referred to as beta-VLDL, are shown in the present study to be mediated by LDL receptors (apoB,E(LDL) receptors), not by unique beta-VLDL receptors. Human blood monocytes cultured for 5-7 d bound apoB- and/or apoE-containing lipoproteins from different species with affinities equivalent to those demonstrated for the receptors on cultured human fibroblasts. Low density lipoproteins competed effectively and completely with 125I-beta-VLDL for binding to and degradation by monocyte-derived macrophages. Specific polyclonal antibodies to bovine apoB,E(LDL) receptors abolished both LDL and beta-VLDL uptake by normal human monocyte-macrophages. Immunoblots of monocyte-macrophage extracts with these antibodies revealed a single protein in human macrophages with an apparent molecular weight identical to that of the apoB,E(LDL) receptor found on human fibroblasts. Like receptors on cultured human fibroblasts, the apoB,E(LDL) receptors on monocyte-macrophages responsible for 125I-beta-VLDL and 125I-LDL uptake were efficiently down regulated by preincubation of the cells with beta-VLDL or LDL. Finally, monocyte-macrophages from seven homozygous familial hypercholesterolemia subjects were unable to metabolize beta-VLDL or LDL, but demonstrated normal uptake of acetoacetylated LDL. The classic apoB,E(LDL) receptors on human monocyte-macrophages thus mediate the uptake of beta-VLDL by these cells.

Comparison of immediate versus day to day variability of ventricular tachycardia induction by programmed stimulation.

The use of programmed stimulation to assess long-term oral antiarrhythmic drug efficacy for ventricular tachycardia is complicated by the fact that mode of ventricular tachycardia induction varies from day to day in the absence of drug therapy. The purpose of this prospective study was to assess whether mode of ventricular tachycardia induction is more reproducible within one study than from day to day. Thirty-nine consecutive patients with documented sustained ventricular tachyarrhythmias secondary to coronary artery disease underwent three inductions of ventricular tachycardia at 15 min intervals in the absence of drug therapy. A stimulation protocol in which the only major variable was the number of extrastimuli required for tachycardia induction was used. Subsequent day to day variability in mode of tachycardia induction was also assessed in the same patients at two further drug-free inductions at intervals of 5 +/- 2 days. The number of extrastimuli required for tachycardia induction was significantly more reproducible at the immediate repeat studies than from day to day (69% of patients versus 31%, p less than 0.01). From these data, probability tables were derived that show the likelihood that changes in inducibility at subsequent tachycardia inductions are due to chance. The QRS configuration of induced ventricular tachycardia was also more reproducible at the immediate studies (64% versus 26%, p less than 0.01). Basic electrophysiologic and stimulation variables differed over a significantly wider range from day to day than at the immediate studies.(ABSTRACT TRUNCATED AT 250 WORDS)