ABSTRACT
INTRODUCTION: We know little about the evolution of perihaematomal oedema (PHO) >24 h after ICH onset. We aimed to determine the trajectory of PHO after ICH onset and its association with outcome. METHODS: We did a prospective cohort study using a pre-specified scanning protocol in adults with first-ever spontaneous ICH and measured absolute PHO volumes on CT head scans at ICH diagnosis and 3 ± 2, 7 ± 2, and 14 ± 2 days after ICH onset. We used the largest ICH if ICHs were multiple. The primary outcomes were (a) the trajectory of PHO after ICH onset and (b) the association between PHO (absolute volume at the time when most repeat CT head scans were obtained, and change in PHO volume at this time compared with the first CT head scan) and poor functional outcome (modified Rankin scale 3-6 at 90 days). We pre-specified multivariable logistic regression models of this association adjusting analyses for potential confounders: age, GCS, infratentorial ICH location, and intraventricular extension. RESULTS: In 106 participants of whom 49 (46%) were female, with a median ICH volume 7 mL (interquartile range [IQR] 2-22 mL), the trajectory of median PHO volume increased from 14 mL (IQR: 7-26 mL) at diagnosis to 18 mL (IQR: 8-40 mL) at 3 ± 2 days (n = 87), 20 mL (IQR: 8-48 mL) at 7 ± 2 days (n = 93) and 21 mL (IQR: 10-54 mL) at 14 ± 2 days (n = 78) (p = <0.001). PHO volume at each time point was collinear with ICH volume at diagnosis (ârâ >0.7), but the change in PHO volume between diagnosis and each time point was not. Given collinearity, we used total lesion (i.e., ICH + PHO) volume instead of PHO volume in a logistic regression model of its association at each time point with outcome. Increasing total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome (adjusted OR per mL 1.02, 95% CI: 1.00-1.03; p = 0.036), but the increase in PHO volume between diagnosis and day 7 ± 2 was not associated with poor functional outcome (adjusted OR per mL 1.03, 95% CI: 0.99-1.07; p = 0.132). CONCLUSION: PHO volume increases throughout the first 2 weeks after onset of mild to moderate ICH. Total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome, but the change in PHO volume between diagnosis and day 7 ± 2 was not. Prospective cohort studies with larger sample sizes are needed to investigate these associations and their modifiers.
ABSTRACT
The tricuspid regurgitation pressure gradient (TRPG) reflects the difference in pressure between the right ventricle and right atrium (ΔPRV-RA). Its estimation by echocardiography correlates well with that obtained using right-heart catheterization. An elevated TRPG is an important marker for identifying right ventricular dysfunction in both the acute and chronic settings. However, in the "wide-open" variant of TR, the TRPG counterintuitively falls. Failure to recognize this potential pitfall and underlying pathophysiology can cause underestimation of the severity of right ventricular dysfunction. This could lead to erroneous fluid tolerance assessments, and potentially harmful resuscitative and airway management strategies. In this manuscript, we illustrate the pathophysiology and potential pitfall of wide-open TR through a series of cases in which emergency physicians made the diagnosis using cardiac point-of-care ultrasound. To our knowledge, this clinical series is the first to demonstrate recognition of the paradoxically-low TRPG of wide-open TR, which guided appropriate management of critically ill patients in the emergency department.
Subject(s)
Echocardiography , Emergency Service, Hospital , Tricuspid Valve Insufficiency , Ventricular Dysfunction, Right , Humans , Tricuspid Valve Insufficiency/diagnostic imaging , Tricuspid Valve Insufficiency/physiopathology , Tricuspid Valve Insufficiency/complications , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/physiopathology , Echocardiography/methods , Male , Female , Middle Aged , Aged , Point-of-Care Systems , AdultABSTRACT
INTRODUCTION: Prehospital identification of intracerebral haemorrhage (ICH) in suspected stroke cases may enable the initiation of appropriate treatments and facilitate better-informed transport decisions. This scoping review aims to examine the literature to identify early clinical features and portable devices for the detection of ICH in the prehospital setting. METHODS: Three databases were searched via Ovid (MEDLINE, EMBASE and CENTRAL) from inception to August 2022 using prespecified search strategies. One reviewer screened all titles, abstracts and full-text articles for eligibility, while a second reviewer independently screened 20% of the literature during each screening stage. Data extracted were tabulated to summarise the key findings. RESULTS: A total of 6803 articles were screened for eligibility, of which 22 studies were included for analysis. Among them, 15 studies reported on early clinical features, while 7 considered portable devices. Associations between age, sex and comorbidities with the presence of ICH varied across studies. However, most studies reported that patients with ICH exhibited more severe neurological deficits (n=6) and higher blood pressure levels (n=11) at onset compared with other stroke and non-stroke diagnoses. Four technologies were identified for ICH detection: microwave imaging technology, volumetric impedance phase shift spectroscopy, transcranial ultrasound and electroencephalography. Microwave and ultrasound imaging techniques showed promise in distinguishing ICH from other diagnoses. CONCLUSION: This scoping review has identified potential clinical features for the identification of ICH in suspected stroke patients. However, the considerable heterogeneity among the included studies precludes meta-analysis of available data. Moreover, we have explored portable devices to enhance ICH identification. While these devices have shown promise in detecting ICH, further technological development is required to distinguish between stroke subtypes (ICH vs ischaemic stroke) and non-stroke diagnoses.
Subject(s)
Brain Ischemia , Emergency Medical Services , Stroke , Humans , Stroke/diagnosis , Cerebral Hemorrhage/diagnostic imagingABSTRACT
The presence of pulmonary hypertension (PH) may affect whether cardiac tamponade physiology develops from a pericardial effusion. Specifically, the increased intracardiac pressure and right ventricular hypertrophy associated with PH would seemingly increase the intrapericardial pressure threshold at which the right-sided chambers collapse. In this systematic review, we examined the impact of PH on the incidence, in-hospital and long-term mortality, and echocardiographic findings of patients with cardiac tamponade. Using the PRISMA guideline, a systematic search was conducted in PubMed, Academic Search Premier, Web of Science, Google Scholar, and the Cochrane Database for studies investigating PH and cardiac tamponade. The Newcastle-Ottawa Scale was used to analyze the quality of returned studies. Primary outcomes included the incidence of cardiac tamponade, as well as in-hospital and long-term mortality rates. Secondary outcomes were the presence or absence of echocardiographic findings of cardiac tamponade in patients with PH. Forty-three studies (9 cohort studies and 34 case reports) with 1054 patients were included. The incidence of cardiac tamponade was significantly higher in patients with PH compared to those without PH, 2.0% (95% CI 1.2-3.2%) vs. 0.05% (95% CI 0.05-0.05%), p < 0.0001, OR 40.76 (95% CI 24.8-66.9). The incidence of tamponade in patients with a known pericardial effusion was similar in those with and without PH, 20.3% (95% CI 12.0-32.3%) and 20.9% (95% CI 18.0-24.1%), p = 0.9267, OR 0.97 (95% CI 0.50-1.87). In patients with tamponade, those with PH demonstrated a significantly higher in-hospital mortality than those without PH, 38.8% (95% CI 26.4-52.8%) vs. 14.4% (95% CI 14.2-14.6%), p < 0.0001, OR 3.77 (95% CI 2.12-6.70). Long-term mortality in patients with tamponade was significantly lower in those with PH than in those without PH, 45.5% (95% CI 33.0-58.5%) vs. 59.1% (95% CI 54.7-63.4%), p = 0.0258, OR 0.576 (95% CI 0.33-1.01). However, after stratifying by non-malignant etiologies, the long-term mortality benefit for those with PH disappeared. In the studies that described specific echocardiographic findings of cardiac tamponade, only 10.5% of patients with PH and tamponade showed right atrial and right ventricular collapse. When evaluating patients with pericardial effusions, physicians must recognize the effects of underlying PH on the incidence, in-hospital and long-term mortality rates, and potentially atypical echocardiographic presentation of cardiac tamponade.
ABSTRACT
Based on a prior university patent, the authors developed a novel type of bioimpedance-based test method to noninvasively detect nonalcoholic fatty liver disease (NAFLD). The development of a new potential NAFLD diagnostic procedure may help to understand the underlying mechanisms between NAFLD and severe liver diseases with a painless and easy-to-use paraclinical examination method, including the additional function to detect even the earlier stages of liver disease. The aim of this study is to present new results and the experiences gathered in relation to NAFLD progress during animal model and human clinical trials.
ABSTRACT
BACKGROUND: Pulmonary embolism (PE) and pulmonary hypertension (PH) are potentially fatal disease states. Early diagnosis and goal-directed management improve outcomes and survival. Both conditions share several echocardiographic findings of right ventricular dysfunction. This can inadvertently lead to incorrect diagnosis, inappropriate and potentially harmful management, and delay in time-sensitive therapies. Fortunately, bedside echocardiography imparts a few critical distinctions. OBJECTIVE: This narrative review describes eight physiologically interdependent echocardiographic parameters that help distinguish acute PE and chronic PH. The manuscript details each finding along with associated pathophysiology and summarization of the literature evaluating diagnostic utility. This guide then provides pearls and pitfalls with high-quality media for the bedside evaluation. DISCUSSION: The echocardiographic parameters suggesting acute or chronic right ventricular dysfunction (best used in combination) are: 1. Right heart thrombus (acute PE) 2. Right ventricular free wall thickness (acute ≤ 5 mm, chronic > 5 mm) 3. Tricuspid regurgitation pressure gradient (acute ≤ 46 mmHg, chronic > 46 mmHg, corresponding to tricuspid regurgitation maximal velocity ≤ 3.4 m/sec and > 3.4 m/sec, respectively) 4. Pulmonary artery acceleration time (acute ≤ 60-80 msec, chronic < 105 msec) 5. 60/60 sign (acute) 6. Pulmonary artery early-systolic notching (proximally-located, higher-risk PE) 7. McConnell's sign (acute) 8. Right atrial enlargement (equal to left atrial size suggests acute, greater than left atrial size suggests chronic). CONCLUSIONS: Emergency physicians must appreciate the echocardiographic findings and associated pathophysiology that help distinguish acute and chronic right ventricular dysfunction. In the proper clinical context, these findings can point towards PE or PH, thereby leading to earlier goal-directed management.
Subject(s)
Atrial Fibrillation , Hypertension, Pulmonary , Pulmonary Embolism , Tricuspid Valve Insufficiency , Ventricular Dysfunction, Right , Humans , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/complications , Tricuspid Valve Insufficiency/complications , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/complications , Atrial Fibrillation/complications , Echocardiography , Pulmonary Embolism/complications , Pulmonary Embolism/diagnostic imagingABSTRACT
INTRODUCTION: The detection of intracerebral haemorrhage (ICH) in the prehospital setting without conventional imaging technology might allow early treatment to reduce haematoma expansion and improve patient outcomes. Although ICH and ischaemic stroke share many clinical features, some may help in distinguishing ICH from other suspected stroke patients. In combination with clinical features, novel technologies may improve diagnosis further. This scoping review aims to first identify the early, distinguishing clinical features of ICH and then identify novel portable technologies that may enhance differentiation of ICH from other suspected strokes. Where appropriate and feasible, meta-analyses will be performed. METHODS: The scoping review will follow the recommendations of the Joanna Briggs Institute Methodology for Scoping Reviews as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A systematic search will be conducted using MEDLINE (Ovid), EMBASE (Ovid) and CENTRAL (Ovid). EndNote reference management software will be used to remove duplicate entries. Two independent reviewers will screen titles, abstracts and full-text reports according to prespecified eligibility criteria using the Rayyan Qatar Computing Research Institute software. One reviewer will screen all titles, abstracts and full-text reports of potentially eligible studies, while the other reviewer will independently screen at least 20% of all titles, abstracts and full-text reports. Conflicts will be resolved through discussion or by consulting a third reviewer. Results will be tabulated in accordance with the scoping review's objectives along with a narrative discussion. ETHICS AND DISSEMINATION: Ethical approval is not required for this review, as it will only include published literature. The results will be published in an open-access, peer-reviewed journal, presented at scientific conferences and form part of a PhD thesis. We expect the findings to contribute to future research into the early detection of ICH in suspected stroke patients.
Subject(s)
Brain Ischemia , Emergency Medical Services , Stroke , Humans , Stroke/diagnosis , Academies and Institutes , Cerebral Hemorrhage/diagnostic imaging , Research Design , Systematic Reviews as Topic , Review Literature as TopicABSTRACT
BACKGROUND/AIMS: To describe baseline characteristics and 12-month outcomes with vascular endothelial growth factor (VEGF) inhibitors of treatment-naïve hemiretinal vein occlusion (HRVO) compared with branch (BRVO) and central (CRVO) variants in routine clinical care. METHODS: A database observational study recruited 79 HRVO eyes, 590 BRVO eyes and 344 CRVO eyes that initiated therapy over 10 years. The primary outcome was mean change in visual acuity (VA-letters read on a logarithm of minimal angle of resolution chart) at 12 months. Secondary outcomes included mean change in central subfield thickness (CST), injections and visits. RESULTS: At baseline, mean VA in HRVO (53.8) was similar to CRVO (51.9; p=0.40) but lower than BRVO (59.4; p=0.009). HRVO eyes improved to match BRVO eyes from soon after treatment started through 12 months. Mean change in VA was greater in HRVO (+16.4) than both BRVO (+11.4; p=0.006) and CRVO (+8.5; p<0.001). Mean change in CST in HRVO (-231 µm) was similar to CRVO (-259 µm; p=0.33) but greater than BRVO eyes (-151 µm; p=0.003). The groups had similar median burdens of eight injections and nine visits. CONCLUSIONS: HRVO generally experienced the greatest mean change in VA of the three types of RVO when treated with VEGF inhibitors, ending with similar 12-month VA and CST to BRVO despite starting closer to CRVO. Inclusion of HRVO in BRVO or CRVO cohorts of clinical trials would be expected to proportionally inflate and skew the visual and anatomic outcomes.
Subject(s)
Macular Edema , Retinal Vein Occlusion , Humans , Vascular Endothelial Growth Factor A , Bevacizumab/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Macular Edema/drug therapy , Intravitreal Injections , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/drug therapy , Blindness , Registries , Treatment OutcomeABSTRACT
INTRODUCTION: Pericardial tamponade requires timely diagnosis and management. It carries a high mortality rate. OBJECTIVE: This review incorporates available evidence to clarify misconceptions regarding the clinical presentation, while providing an in-depth expert guide on bedside echocardiography. It also details the decision-making strategy for emergency management including pericardiocentesis, along with pre- and peri-procedural pearls and pitfalls. DISCUSSION: Pericardial effusions causing tamponade arise from diverse etiologies across acute and sub-acute time courses. The most frequently reported symptom is dyspnea. The classically taught Beck's triad (which includes hypotension) does not appear commonly. Echocardiographic findings include: a pericardial effusion (larger size associated with tamponade), diastolic right ventricular collapse (specific), systolic right atrial collapse (sensitive), a plethoric non-collapsible inferior vena cava (sensitive), and sonographic pulsus paradoxus. Emergent pericardiocentesis is warranted by hemodynamic instability, impending deterioration, or cardiac arrest. Emergent surgical indications include type A aortic dissection causing hemopericardium, ventricular free wall rupture after acute myocardial infarction, severe chest trauma, and iatrogenic hemopericardium when bleeding cannot be controlled percutaneously. Pre-procedure management includes blood products for patients with traumatic hemopericardium; gentle intravenous fluids to hypotensive, hypovolemic patients with consideration for vasoactive medications; treatment of anticoagulation, coagulopathies, and anemia. Positive-pressure ventilation and intravenous sedation can lower cardiac output and should be avoided if possible. Optimal location for echocardiography-guided pericardiocentesis is the largest, shallowest fluid pocket with no intervening vital structures. Patient positioning to prevent hypoxia and liberal amounts of local anesthesia can facilitate patients remaining still. Safe needle guidance and confirmation of catheter placement is achieved using low-depth sonographic views, injection of agitated saline, and evaluation of initial aspirate for hemorrhage. Pericardial fluid should be drained slowly to avoid pericardial decompression syndrome. CONCLUSION: An understanding of the pathophysiology, clinical presentation, echocardiographic findings, and time-sensitive management of pericardial tamponade is essential for emergency physicians.
Subject(s)
Cardiac Tamponade , Emergency Medicine , Hypotension , Pericardial Effusion , Cardiac Tamponade/diagnostic imaging , Cardiac Tamponade/etiology , Cardiac Tamponade/therapy , Echocardiography , Humans , Hypotension/complications , Pericardial Effusion/diagnostic imaging , Pericardial Effusion/etiology , Pericardial Effusion/therapy , Pericardiocentesis/methodsABSTRACT
In the last 6 years, following the first pathological description of presumed amyloid-beta (Aß) transmission in humans (in 2015) and subsequent experimental confirmation (in 2018), clinical cases of iatrogenic cerebral amyloid angiopathy (CAA)-attributed to the transmission of Aß seeds-have been increasingly recognised and reported. This newly described form of CAA is associated with early disease onset (typically in the third to fifth decade), and often presents with intracerebral haemorrhage, but also seizures and cognitive impairment. Although assumed to be rare, it is important that clinicians remain vigilant for potential cases, particularly as the optimal management, prognosis, true incidence and public health implications remain unknown. This review summarises our current understanding of the clinical spectrum of iatrogenic CAA and provides a diagnostic framework for clinicians. We provide clinical details for three patients with pathological evidence of iatrogenic CAA and present a summary of the published cases to date (n=20), identified following a systematic review. Our aims are: (1) To describe the clinical features of iatrogenic CAA, highlighting important similarities and differences between iatrogenic and sporadic CAA; and (2) To discuss potential approaches for investigation and diagnosis, including suggested diagnostic criteria for iatrogenic CAA.
ABSTRACT
INTRODUCTION: Evidence supports an ultrasound-guided approach in patients with difficult vascular access. Prior research on teaching ultrasound-guided intravenous access has included only small groups of first- and second-year medical students. METHODS: We enrolled fourth-year medical students in our teaching module. The module featured a 6-minute prelearning narrated lecture and 5-minute orientation, followed by ultrasound-guided IV placement on homemade gel models. Facilitators were emergency medicine (EM) residents with a prespecified level of procedural ultrasound skills according to EM milestones. Students completed pre- and postmodule surveys. Facilitators completed the Directly Observed Procedural Skills Evaluation. Primary outcomes included global rating, proficiency on six procedural skills, and perceived learning. RESULTS: Our module was completed by 150 fourth-year medical students (94% of the class); 84% cannulated the vein in one attempt. We used a global rating scale to describe the students' cannulation abilities; 59% were trusted to perform this procedure with direct supervision and coaching, 29% with indirect supervision, and 8% without supervision. There was no association between a student's order of attempting IV access within the group and global rating (p = .41). Students reported increased understanding of indications, antecubital anatomy, sonographic anatomy, and procedural comfort (12%, 29%, 38%, and 65% improvement pre- vs. postmodule, respectively; p < .001). DISCUSSION: Our module enabled more than one-third of fourth-year medical students to achieve an indirect supervision or better level of proficiency in ultrasound-guided IV access, with significant improvements in perceived knowledge. This module may be useful for other educators facilitating the transition to residency.
Subject(s)
Emergency Medicine , Students, Medical , Clinical Competence , Emergency Medicine/education , Humans , Ultrasonography , Ultrasonography, InterventionalABSTRACT
The effect of flavonoid-rich food, such as blueberries, on cognitive function has been subject to a growing amount of research interest in recent years. Epidemiological, prospective, preclinical, and clinical trials have revealed positive cognitive benefits from flavonoid interventions, particularly in relation to the amelioration of cognitive decline in older adults. This review will specifically consider the existing clinical research from both acute and chronic blueberry interventions on cognition in human subjects. The results of 11 studies are reported with 4 studies considering blueberry intervention with children aged 7-10 years, 4 considering adults aged 60 years and older, and 3 considering adults suffering from mild cognitive impairment (MCI). Findings from these studies indicate that cognitive benefits may be found for delayed memory and executive function in children and for delayed memory, executive function, and psychomotor function in older healthy and MCI adults. There is less evidence to suggest positive benefits of blueberry intervention on working memory. Recommendations for future research, including dose used, cognitive tasks, and age groups considered, are proposed.
Subject(s)
Aging , Blueberry Plants , Cognition/drug effects , Executive Function/drug effects , Flavonoids/pharmacology , Aging/drug effects , Aging/psychology , Humans , Plants, Medicinal , Repression, PsychologyABSTRACT
The authors present a case of a 67-year-old male patient, who previously had been diagnosed with a malignant liver tumor localized in segment II. He underwent bisegmentectomy (II and III) and partial IV segmentectomy. After the primary surgery jaundice developed, the level of bilirubin increased and after several imaging modalities reoperation was indicated. During the surgery a rare bile duct anatomy variant was found. The right hepatic duct joined the left duct in the parenchyma of the left lobe, and was ligated at the resection. As the liver hilum was not explored, the absence of the right duct was not discovered. Reconstruction of the biliary system was accomplished by a Roux-en-Y loop.
Subject(s)
Anastomosis, Roux-en-Y/methods , Biliary Tract Surgical Procedures/methods , Hepatectomy/methods , Hepatic Duct, Common/abnormalities , Plastic Surgery Procedures/methods , Aged , Hepatic Duct, Common/surgery , Humans , Incidental Findings , Liver Neoplasms/surgery , Male , ReoperationABSTRACT
The genome sequence of V. cholerae O1 Biovar Eltor strain N16961 has revealed a putative antibiotic resistance (var) regulon that is predicted to encode a transcriptional activator (VarR), which is divergently transcribed relative to the putative resistance genes for both a metallo-ß-lactamase (VarG) and an antibiotic efflux-pump (VarABCDEF). We sought to test whether these genes could confer antibiotic resistance and are organised as a regulon under the control of VarR. VarG was overexpressed and purified and shown to have ß-lactamase activity against penicillins, cephalosporins and carbapenems, having the highest activity against meropenem. The expression of VarABCDEF in the Escherichia coli (ΔacrAB) strain KAM3 conferred resistance to a range of drugs, but most significant resistance was to the macrolide spiramycin. A gel-shift analysis was used to determine if VarR bound to the promoter regions of the resistance genes. Consistent with the regulation of these resistance genes, VarR binds to three distinct intergenic regions, varRG, varGA and varBC located upstream and adjacent to varG, varA and varC, respectively. VarR can act as a repressor at the varRG promoter region; whilst this repression was relieved upon addition of ß-lactams, these did not dissociate the VarR/varRG-DNA complex, indicating that the de-repression of varR by ß-lactams is indirect. Considering that the genomic arrangement of VarR-VarG is strikingly similar to that of AmpR-AmpC system, it is possible that V. cholerae has evolved a system for resistance to the newer ß-lactams that would prove more beneficial to the bacterium in light of current selective pressures.
Subject(s)
Anti-Bacterial Agents/metabolism , Gene Expression Regulation, Bacterial , Membrane Transport Proteins/genetics , Regulon , Transcription Factors/metabolism , Vibrio cholerae/genetics , beta-Lactamases/genetics , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Anti-Bacterial Agents/pharmacology , Base Sequence , DNA, Intergenic , Drug Resistance, Bacterial , Genes, Bacterial , Hydrolysis , Kinetics , Microbial Sensitivity Tests , Promoter Regions, Genetic , Protein Binding , Transcription, Genetic , Vibrio cholerae/drug effects , Vibrio cholerae/metabolismABSTRACT
LINGO-1 (leucine rich repeat and Ig domain containing Nogo receptor interacting protein-1) is a central nervous system transmembrane protein which simultaneously interacts with the Nogo-66 receptor and p75(NTR) or TROY on neurons to form a receptor complex responsible for myelin-mediated neurite outgrowth inhibition. On oligodendroglial cells, LINGO-1 interacts with p75(NTR) to constitutively inhibit multiple aspects of oligodendrocyte differentiation. Recently, LINGO-1 was identified as an in vivo interacting partner of the amyloid precursor protein (APP) and, correspondingly, cellular LINGO-1 expression was found to augment the release of the Abeta peptide, the potential causative agent of Alzheimer's disease. In addition, the recombinant LINGO-1 ectodomain has been shown to self-interact in solution and after crystallisation. Here, we have used deletional mutagenesis to identify the regions on LINGO-1 that are involved in homo- and heterotypic interactions. We have found that the N-terminal region containing the leucine-rich repeats along with the transmembrane and cytoplasmic domains of LINGO-1 are not required for self-interaction or interaction with APP.
Subject(s)
Amyloid beta-Protein Precursor/metabolism , Leucine/metabolism , Membrane Proteins/chemistry , Membrane Proteins/metabolism , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/metabolism , Humans , Leucine/genetics , Membrane Proteins/genetics , Nerve Tissue Proteins/genetics , Protein Binding , Protein Structure, Tertiary , Sequence Deletion/geneticsABSTRACT
LINGO-1 is a potent negative regulator of oligodendrocyte differentiation and hence may play a pivotal restrictive role during remyelination in demyelinating diseases such as multiple sclerosis. However, little is known as to which stages of oligodendrocyte differentiation are inhibited by LINGO-1, which domains of the protein are involved and whether accessory proteins are required. Here, we show that LINGO-1 expression in the human oligodendroglial cell line MO3.13 inhibited process extension and this was reversed by an anti-LINGO-1 antibody or the antagonist LINGO-1-Fc. LINGO-1 expression was also found to inhibit myelin basic protein transcription in the rat oligodendroglial cell line CG4. Both of these inhibitory actions of LINGO-1 were abrogated by deletion of the entire ectodomain or cytoplasmic domains but, surprisingly, were unaffected by deletion of the leucine-rich repeats (LRRs). As in neurons, LINGO-1 physically associated with endogenous p75(NTR) in MO3.13 cells and, correspondingly, its inhibition of process extension was reversed by antagonists of p75(NTR). Thus, LINGO-1 inhibits multiple aspects of oligodendrocyte differentiation independently of the LRRs via a process that requires p75(NTR) signalling.
Subject(s)
Cell Differentiation/physiology , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Oligodendroglia/cytology , Oligodendroglia/metabolism , Receptor, Nerve Growth Factor/metabolism , Animals , Blotting, Western , Cell Line , Cell Separation , Flow Cytometry , Humans , Immunoprecipitation , Myelin Basic Protein/metabolism , Rats , Reverse Transcriptase Polymerase Chain Reaction , Transcription, GeneticABSTRACT
BACKGROUND: Nonablative fractional photothermolysis has revolutionized the way we treat a number of common skin conditions with laser technology. OBJECTIVE: A comprehensive guide is needed for clinicians using this technology to treat specific skin conditions in various skin types. MATERIALS AND METHODS: Recommendations were made from a recent round table discussion among experienced physicians and a review of recent literature findings. RESULTS: Optimal laser parameters are dependent on patient skin type and condition. We recommended guidelines for the successful treatment of several common skin conditions on and off the face using nonablative fractional photothermolysis. Specific conditions were dyschromia, rhytides, acne scars, surgical scars, melasma, and striae distensae. CONCLUSIONS: We developed reproducible guidelines to most effectively treat a variety of skin types and conditions using nonablative fractional photothermolysis. Future large, multicenter trials are indicated for further optimization of treatment parameters.
Subject(s)
Dermatologic Surgical Procedures , Laser Therapy/methods , Lasers, Solid-State/therapeutic use , Plastic Surgery Procedures/methods , Practice Guidelines as Topic , Skin Diseases/surgery , Acne Vulgaris/complications , Anesthesia, Local/methods , Calibration , Cicatrix/etiology , Cicatrix/surgery , Equipment Design , Face/surgery , Humans , Laser Therapy/instrumentation , Lasers, Solid-State/adverse effects , Melanosis/surgery , Patient Selection , Premedication/methods , Rhytidoplasty/methods , Skin AgingABSTRACT
PURPOSE: To determine whether patients with age-related macular degeneration (ARMD) benefit from cataract surgery and to assess the risk of progression of preexisting maculopathy 4 and 12 months postoperatively. SETTING: Princess Alexandra Eye Pavilion, Royal Infirmary of Edinburgh, Edinburgh, Scotland. METHODS: Two groups of patients were evaluated prospectively. The study group comprised patients with ARMD scheduled to have cataract surgery (n = 40). The control group comprised patients with ARMD not having cataract surgery (n = 43). Patients were assessed at baseline (preoperatively) and 4 and 12 months postoperatively. Assessment included visual function tests and quality of life (QoL) measures. The mean values for each item tested were obtained for each group at each visit, and comparisons between visits were done using the Wilcoxon signed rank test. RESULTS: There were significant benefits of cataract surgery in terms of visual function and QoL measures at 4 and 12 months. There was no increased risk of progression of maculopathy in the study group. There were no significant differences in the items tested in the control group. CONCLUSIONS: One year postoperatively, QoL benefits were maintained in the study group and there was no increased risk of progression of maculopathy in patients with mild and moderate degrees of ARMD. Larger numbers of patients must be assessed prospectively for longer periods to determine the relative risk of progression of different stages of ARMD after cataract surgery.