Endomyocardial fibrosis (EMF) is a disease that is characterized by fibrosis of the apical endocardium of the right ventricle (RV), left ventricle (LV), or both.
The clinical manifestations are largely related to the consequences of restrictive ventricular filling, including left and right sided heart failure.
The heart failure is associated with atrioventricular-valve regurgitation.
Endomyocardial fibrosis is a major cause of illness and death in areas where it is endemic, and in its severest form carries a very poor prognosis, with an estimated survival of 2 years after diagnosis.
amyloid .cardiac amyloidosis. Pathogenetic steps in the development of amyloid diseases.AL amyloidosis. ATTR amyloidosis.ATTRwt amyloidosis.
Potential for misdiagnosis of amyloidosis
amyloid .cardiac amyloidosis. Pathogenetic steps in the development of amyloid diseases.AL amyloidosis. ATTR amyloidosis.ATTRwt amyloidosis.
Potential for misdiagnosis of amyloidosis
A comprehensive approach to Atrial Fibrillation. Everything you need to know about Atrial fibrillation. Including recent 2014 AHA guidelines of management.
Wolff–Parkinson–White syndrome (WPW) is one of several disorders of the conduction system of the heart that are commonly referred to as pre-excitation syndromes. WPW is caused by the presence of an abnormal accessory electrical conduction pathway between the atria and the ventricles. Electrical signals travelling down this abnormal pathway (known as the bundle of Kent) may stimulate the ventricles to contract prematurely, resulting in a unique type of supraventricular tachycardia referred to as an atrioventricular reciprocating tachycardia.The incidence of WPW is between 0.1% and 0.3% in the general population.Sudden cardiac death in people with WPW is rare (incidence of less than 0.6%), and is usually caused by the propagation of an atrial tachydysrhythmia (rapid and abnormal heart rate) to the ventricles by the abnormal accessory pathway.
Review of a rare but important cardiac dysplasia causing high mortality and morbidity in mostly young patients.
In this presentation, the epidemiology, pathophysiology, diagnosis and treatment of said disease is examines.
ENDOMYOCARDIAL FIBROSIS BY MIEBAKA FAITHFUL DANIEL.pptxDanielFaithful
Endomyocardial fibrosis is a cardiac disease that with a global incidence but more preponderant in the Tropic.
The disease has been known for more than 70 years, in this review, Dr. Daniel Faithful Miebaka provides a detailed presentation of the condition and some tropical insights.
A comprehensive approach to Atrial Fibrillation. Everything you need to know about Atrial fibrillation. Including recent 2014 AHA guidelines of management.
Wolff–Parkinson–White syndrome (WPW) is one of several disorders of the conduction system of the heart that are commonly referred to as pre-excitation syndromes. WPW is caused by the presence of an abnormal accessory electrical conduction pathway between the atria and the ventricles. Electrical signals travelling down this abnormal pathway (known as the bundle of Kent) may stimulate the ventricles to contract prematurely, resulting in a unique type of supraventricular tachycardia referred to as an atrioventricular reciprocating tachycardia.The incidence of WPW is between 0.1% and 0.3% in the general population.Sudden cardiac death in people with WPW is rare (incidence of less than 0.6%), and is usually caused by the propagation of an atrial tachydysrhythmia (rapid and abnormal heart rate) to the ventricles by the abnormal accessory pathway.
Review of a rare but important cardiac dysplasia causing high mortality and morbidity in mostly young patients.
In this presentation, the epidemiology, pathophysiology, diagnosis and treatment of said disease is examines.
ENDOMYOCARDIAL FIBROSIS BY MIEBAKA FAITHFUL DANIEL.pptxDanielFaithful
Endomyocardial fibrosis is a cardiac disease that with a global incidence but more preponderant in the Tropic.
The disease has been known for more than 70 years, in this review, Dr. Daniel Faithful Miebaka provides a detailed presentation of the condition and some tropical insights.
Complicated Tubercular Pericarditis Presenting as Ventricular Apical Aneurysm...Crimsonpublisherssmoaj
A 25 year old female presented with features of right heart failure. She was treated for pulmonary tuberculosis in the past and completed treatment four years back. Contrast enhanced CT scan of the thorax was performed which revealed chronic calcific peri-carditis with a narrow necked left ventricular apical free wall aneurysm (Figure 1a & 1b). Small contrast filled out-pouching involving the ventricular apex (bold black arrow) showing a narrow neck (thin black arrow). Reduced size of ventricles with prominence of both atria is seen.
https://crimsonpublishers.com/smoaj/fulltext/SMOAJ.000504.php
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Meadows Syndrome as Manifested by Displaced Ischemia of the Lower Limbsemualkaira
Peripartum cardiomyopathy (PPMC) or Meadows syndrome is recognised as a major cause of pregnancy-related heart failure with
high morbidity and mortality. It is a condition of unknown aetiology that manifests itself as heart failure due to systolic dysfunction
of the left ventricle during the last month of pregnancy and up to 5
months after delivery.
Meadows Syndrome as Manifested by Displaced Ischemia of the Lower Limbsemualkaira
Peripartum cardiomyopathy (PPMC) or Meadows syndrome is recognised as a major cause of pregnancy-related heart failure with
high morbidity and mortality. It is a condition of unknown aetiology that manifests itself as heart failure due to systolic dysfunction
of the left ventricle during the last month of pregnancy and up to 5
months after delivery
Meadows Syndrome as Manifested by Displaced Ischemia of the Lower Limbsemualkaira
Peripartum cardiomyopathy (PPMC) or Meadows syndrome is recognised as a major cause of pregnancy-related heart failure with
high morbidity and mortality. It is a condition of unknown aetiology that manifests itself as heart failure due to systolic dysfunction
of the left ventricle during the last month of pregnancy and up to 5
months after delivery.
Meadows Syndrome as Manifested by Displaced Ischemia of the Lower Limbsemualkaira
Peripartum cardiomyopathy (PPMC) or Meadows syndrome is recognised as a major cause of pregnancy-related heart failure with
high morbidity and mortality. It is a condition of unknown aetiology that manifests itself as heart failure due to systolic dysfunction
of the left ventricle during the last month of pregnancy and up to 5
months after delivery
Meadows Syndrome as Manifested by Displaced Ischemia of the Lower Limbsemualkaira
Peripartum cardiomyopathy (PPMC) or Meadows syndrome is recognised as a major cause of pregnancy-related heart failure with
high morbidity and mortality. It is a condition of unknown aetiology that manifests itself as heart failure due to systolic dysfunction
of the left ventricle during the last month of pregnancy and up to 5
months after delivery.
Meadows Syndrome as Manifested by Displaced Ischemia of the Lower Limbsemualkaira
Peripartum cardiomyopathy (PPMC) or Meadows syndrome is recognised as a major cause of pregnancy-related heart failure with
high morbidity and mortality. It is a condition of unknown aetiology that manifests itself as heart failure due to systolic dysfunction
of the left ventricle during the last month of pregnancy and up to 5
months after delivery
The lecture is for medical student. It is from Dr RUSINGIZA Emmanuel, MD, senior lecture at UR( UNIVERSITY OF RWANDA) .
It will help to understand heart diseases in newborn, infants and children.
A Rare Case of Hypertrophic Cardiomyopathy Associated with Congenital Mitral ...asclepiuspdfs
Hypertrophic obstructive cardiomyopathy is mostly associated with mitral insufficiency rather than mitral stenosis. This association is very rare and no cases have been reported in Africa. Our case was about 22-month-old female child that was referred with a 1-year history of tachypnea and III to IV class of dyspnea. Transthoracic echocardiography showed serious mitral stenosis and a mean gradient of 27 mmHg. The interventricular septum was hypertrophic with a width of 8.5 mm with small aortic annulus, leading subaortic stenosis with a mean gradient of 73 mmHg. There was also a severe pulmonary hypertension at 79 mmHg. It was expected to doing a standard septal myectomy and mitral valve replacement.
Central Nervous System Histoplasmosis Related to Bioprosthetic Endocarditisasclepiuspdfs
Endocarditis caused by Histoplasma capsulatum is a rare occurrence. Involvement of the central nervous system by Histoplasma is also relatively uncommon. This paper reports a case of a 62-year-old woman with a past medical history significant for a myocardial infarct 5 years prior which necessitated coronary artery bypass graft surgery, prosthetic aortic valve replacement 4 years prior, and sarcoidosis, diagnosed 1 year prior, which was treated with methotrexate. She presented with fevers, generalized weakness, night sweats, and chest and throat pain. An echocardiogram done as part of her evaluation showed a vegetation on her prosthetic aortic valve. H. capsulatum was identified on blood cultures, and she was started on antibiotics. She expired shortly thereafter. At autopsy, a diagnosis of Histoplasma endocarditis was confirmed with evidence of embolic disease involving kidneys and digits of the hand. Hilar lymph nodes showed evidence of the fungus. Examination of the brain showed multiple widespread microscopic foci of macrophages, lymphocytes, and microglial cells with associated Histoplasma organisms, highlighted on Gomori methenamine silver staining. This paper will discuss central nervous system involvement by Histoplasma.
Treatment strategies in patients with statin intoleranceVishwanath Hesarur
Statins are among the most prescribed drugs in the world and are first-line therapy in the management of hyperlipidemia.
Their beneficial effects on cardiovascular morbidity and mortality have been demonstrated both in primary and in secondary prevention.
They are generally safe, but in some patients, statin therapy is stopped because of intolerance to the drug that may result in muscle aches and weakness, gastrointestinal symptoms, liver enzyme abnormalities, or other nonspecific discomforts.
The rate of reported statin-related events is about 5% to 10% in randomized, placebo controlled clinical trials.
The age, creatinine, and ejection fraction score to riskVishwanath Hesarur
CTOs are the most challenging coronary lesions for PCI, with a success rate ranging from 55% to 100%.
Successful PCI of CTOs is associated with improved long-term clinical outcomes compared with conservative management.
Nevertheless, the clinical outcome even after successful recanalization remains worse compared with patients with non-CTO stenoses who underwent PCI.
New class of therapeutic agents called soluble guanylate cyclase (sGC) stimulators.
Impairment of NO synthesis and signaling through the NO-sGC–cGMP pathway is involved in the pathogenesis of pulmonary hypertension.
Dual mode of action,
Directly stimulating sGC independently of NO, and
Increasing the sensitivity of sGC to NO.
vasorelaxation , antiproliferative and antifibrotic effects
Ionizing radiation makes invasive cardiology procedures such as coronary angiography, percutaneous coronary intervention (PCI), and electrophysiologic diagnostics and therapeutics possible .
Radiation risks can be thought of as deterministic (effects after exceeding certain threshold, e.g., skin burns) or stochastic (a risk of an outcome is proportional to the dose received, e.g., malignancy or teratogenicity) .
Reducing the radiation exposure in the cardiac catheterization laboratory is important, especially as procedures are becoming more complex .
Pre hospital reduced-dose fibrinolysis followed by pciVishwanath Hesarur
Extensive investigations of treatment strategies for patients with STEMIs have led to many improvements in care.
Yet optimal treatment strategies for patients aged ≥75 years with STEMIs are much less clear, and many knowledge gaps remain.
Age ≥75 years is an independent predictor of 30-day mortality in STEMI.
Although this higher mortality risk generally would dictate more aggressive treatments, recent data have shown, for example, that <1/2 of patients aged ≥80 years with STEMIs are treated with any reperfusion therapies at all.
Risk stratification remains central to implement appropriate therapeutic measures for patients with NSTEMI.
The ECG provides rapid risk assessment for patients presenting with chest pain that permits their allocation to appropriate management algorithms to improve the outcomes
Inflammation plays a crucial role in the initiation and progression of atherosclerotic disease.
Monocyte chemoattractant protein-1 (MCP-1) is a member of the C-C chemokine family that is produced by monocytes or macrophages, smooth muscle cells, and endothelial cells within atherosclerotic plaques.
In addition to its established role in the pathogenesis of atherosclerotic disease progression and plaque rupture, MCP-1 is also involved in the reparative response, such as arteriolar remodeling and restenosis after an acute coronary event.
The rapid increase in energy drink (ED) consumption has stimulated growing public concern with adverse events related to ED consumption.
The US Substance Abuse Services and Mental Health Administration has reported that over a 4-year period from 2007 to 2011, emergency department visits related to EDs more than doubled to >20,000 visits annually.
Most of the adverse effects and toxicities associated with EDs have been attributed to the high caffeine content of EDs.
Thrombus aspiration during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is said to reduce PCI-induced distal occlusion.
In an attempt to enhance its effectiveness, thrombus aspiration is often coupled with glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors, although conflicting results with this strategy have been reported.
GP IIb/IIIa antagonists inhibit the final common pathway that leads to platelet aggregation and leukocyte plugging, which are the main components of fresh thrombi.
Primary PCI with stenting immediately after coronary reperfusion salvage procedures jeopardizes myocardium, improves prognosis, and is the current standard of care for acute STEMI .
No-reflow is defined as an acute reduction in myocardial blood flow despite a patent epicardial coronary artery .
The pathophysiology of no-reflow involves microvascular obstruction secondary to distal embolization of clot, microvascular spasm, and thrombosis .
No-reflow occurs in ~10% of cases of primary PCI and is associated with patient characteristics such as advanced age and delayed presentation and coronary characteristics such as a completely occluded culprit artery and heavy thrombus burden .
CHRONIC ASPIRIN AND STATIN THERAPYIN PATIENTS WITH IMPAIRED RENAL FUNCTIONA...Vishwanath Hesarur
Chronic use of aspirin and statin may reduce the risk of subsequent MI and improve outcome in patients with documented IHD or in patients at high risk of a first cardiovascular event.
Moreover, previous aspirin & statin therapy may interfere with the clinical presentation of acute MI, with a higher incidence of NSTEMI as compared to STEMI.
Bivalirudin in acute coronary syndromes and percutaneous coronaryVishwanath Hesarur
Anti-thrombotic therapy remains a cornerstone in per-cutaneous coronary intervention (PCI) and acute coronary syndrome (ACS) management.
The search for newer anti-thrombotic drugs is ongoing with the goal to achieve an agent which leads to less bleeding complications without a reduction or indeed improvement in clinical efficacy, resulting in net clinical benefit.
This is because major bleeding remains a significant risk factor for mortality following PCI with higher 30 days and one year mortality reported in numerous studies .
Bleeding is associated with a five-fold increase in mor-tality and higher risk of myocardial infarction, stroke and stent thrombosis in ACS .
Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia.
Several distinct types of DM are caused by a complex interaction of genetics and environmental factors.
Depending on the etiology of the DM, factors contributing to hyperglycemia include reduced insulin secretion, decreased glucose utilization, and increased glucose production.
The metabolic dysregulation associated with DM causes secondary pathophysiologic changes in multiple organ systems that impose a tremendous burden on the individual with diabetes and on the health care system.
Based on the principle that the distal coronary pressure measured during vasodilation is directly proportional to maximum vasodilated perfusion.
FFR is defined as the ratio of maximum blood flow in a stenotic artery to maximum blood flow in the same artery if there were no stenosis.
FFR is simply calculated as a ratio of mean pressure distal to a stenosis (Pd) to the mean pressure proximal stenosis, that is the mean pressure in the aorta (Pa), during maximal hyperaemia.
TAPVC defines the anomaly in which the pulmonary veins have no connection with the left atrium. Rather, the pulmonary veins connect directly to one of the systemic veins (TAPVC) or drain in to right atrium.
A PFO or ASD is present essentially in those who survive after birth
When pulmonary veins drain anomalously into the right atrium either because of complete absence of the interatrial septum or malattachment of the septum primum , then it is known as total anomalous pulmonary venous drainage.
When some or all of the pulmonary veins drain anomalously in to RA or its tributaries without being abnormally connected, the terms partially anomalous pulmonary venous drainage (PAPVD) or totally anomalous pulmonary venous drainage (TAPVD) with normal pulmonary venous connections are used.
A heart transplant, or a cardiac transplant, is a surgical transplant procedure performed on patients with end-stage heart failure or severe coronary artery disease. As of 2008 the most common procedure is to take a working heart from a recently deceased organ donor (cadaveric allograft) and implant it into the patient. The patient's own heart is either removed (orthotopic procedure) or, less commonly, left in place to support the donor heart (heterotopic procedure). Post-operation survival periods average 15 years. Heart transplantation is not considered to be a cure for heart disease, but a life-saving treatment intended to improve the quality of life for recipients
Persistent truncus arteriosus (or patent truncus arteriosus), also known as Common arterial trunk, is a rare form of congenital heart disease that presents at birth. In this condition, the embryological structure known as the truncus arteriosus fails to properly divide into the pulmonary trunk and aorta. This results in one arterial trunk arising from the heart and providing mixed blood to the coronary arteries, pulmonary arteries, and systemic circulation
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
2. INTRODUCTION
Endomyocardial fibrosis (EMF) is a disease that is
characterized by fibrosis of the apical endocardium of the
right ventricle (RV), left ventricle (LV), or both.
The clinical manifestations are largely related to the
consequences of restrictive ventricular filling, including
left and right sided heart failure.
The heart failure is associated with atrioventricular-valve
regurgitation.
Endomyocardial fibrosis is a major cause of illness and
death in areas where it is endemic, and in its severest form
carries a very poor prognosis, with an estimated survival of
2 years after diagnosis.
3. HISTORY
1946: Bedford and Konstam described a form of heart
disease in 40 West African soldiers -post-mortem revealed
subendocardial fibrosis with features that are now
associated with EMF.
1946: Davies JN first coined the term EMF and said that “he
became convinced rightly or wrongly that he had met a
new disease”.
1938 : Arthur Williams had described two cases of mitral
incompetence and correlated with large patches of fibrosis
affecting the ventricular walls at necropsy
4. 1946 : Davies did his MD thesis on this disease where he
described the pathological features as a distinct entity.
1948 : Bedford encouraged davies to publish his observations and
Arthur Williams and JD Ball were his co-authors.
Later, JD Ball, with his missionary job joined Christian Medial
College Vellore in India and identified the pathological
specimens at autopsy which he shipped to Davies for
confirmation.
Thus, the disease was reported from India for the first time
1954 : Davies described the classical four pathological features of
EMF and its distribution in Africa.
Right and left ventricular endocardial fibrosis, affecting the apex
and inflow region with atrioventricular valve regurgitations
The disease came to be known as the Davies’ disease.
5. 1960 : Samuel and Anklesaria published this initial autopsy
series from south India.
1962 : CK Gopi from Trivandrum, described the specimen
kept in the hospital autopsied in 1950s as a case of right
ventricular endomyocardial fibrosis with right atrial
thrombi.
6. EPIDEMIOLOGY
EMF is a disorder found typically in tropical and
subtropical Africa, notably in Uganda, Nigeria, and
Mozambique
Major cause of morbidity and mortality, accounting for
25% of cases of congestive heart failure and death in
equatorial Africa.
A population-based study in rural Mozambique revealed a
prevalence of the disorder affecting 19.8% of the
population.
7. The disease is increasingly recognized in other tropical and
subtropical regions within 15 degrees of the equator,
including India, Brazil, Colombia, and Sri Lanka.
8. Increased incidence among individuals of low socioeconomic status.
Male preponderance, is most common in children and young
adults, but has been described in individuals into the sixth decade of
life .
9. ETIOLOGY
The cause of the underlying fibrotic process of EMF is largely
unknown; however, several theories exist and are briefly
reviewed
Eosinophilia
Most commonly cited etiologic link in EMF.
In support - observed that EMF resembles a late stage of
Loeffler's endocarditis (eosinophilic myocarditis) , a process
known to result from sustained eosinophilia in patients with
hypereosinophilic syndrome .
EMF and intraventricular thrombosis have also been observed
following a variety of other eosinophilic syndromes including
hypersensitivity myocarditis , parasitic infections , eosinophilic
leukemia, sarcoma, carcinoma, and lymphoma .
10. Despite the similarities between Loeffler’s endocarditis and
EMF, serum and myocardial eosinophilia have not been
consistently demonstrated in EMF.
one study from Uganda found - 60 % of patients with EMF
had at least mild eosinophilia at the time of diagnosis
compared to 10 % of controls , in Kerala, India, most with
EMF did not have active eosinophilia at the time of
diagnosis.
Endomyocardial biopsies have not demonstrated
eosinophilia in EMF, even in those suspected to have early
disease .
11. Infectious
Several infections - toxoplasmosis , rheumatic fever , malaria , and
helminthic parasites .
A consistent association with one organism, however, has not been
demonstrated.
Environmental exposure
Cerium, a rare earth element, has been postulated to play a role in the
pathogenesis of EMF.
Serum levels of cerium are high in patients with EMF compared to
controls, and it is postulated that cerium is ingested from food and
contaminated soil .
The incidence of EMF is decreasing in India, which corresponds with a
reduction in soil cerium that has occurred with modernization.
12. Immunologic
The presence of anti-myosin autoantibodies has been
demonstrated in EMF; however, these antibodies can be
detected in other forms of heart disease such as Dresser’s
syndrome, rheumatic heart disease, and in patients with
post-transplant rejection.
Genetic
A familial link has been identified in many studies;
however, it is not known whether this is due to an
environmental or genetic cause or both.
13. PATHOLOGY
EMF affects both the right and left ventricles in
approximately 50% of patients, purely the left in 40%, and
the right ventricle alone in the remaining 10%.
The typical gross appearance is that of a normal to slightly
enlarged heart.
The right atrium may be dilated in proportion to the
severity of right ventricular involvement.
The hallmark feature of the disorder is fibrotic obliteration
of the apex of the affected ventricle .
14. The fibrosis involves the papillary muscles and chordae
tendineae, leading to atrioventricular valve distortion and
regurgitation.
In the left ventricle, the fibrosis extends from the apex to
the posterior mitral valve leaflet, usually sparing the
anterior mitral leaflet and the ventricular outflow tract.
Endocardial calcific deposits can be present involving
diffuse areas of the ventricle.
The fibrotic tissue often creates a nidus for thrombus
formation, which can be extensive. Atrial thrombi also
occur.
The process usually does not involve the epicardium, and
the coronary artery obstruction is distinctly uncommon.
15. End-stage endomyocardial disease . Apical ventricular thrombi form in damaged
endocardium, and progressive endomyocardial fibrosis entraps the chordae
tendineae, leading to mitral and sometimes tricuspid valvular incompetence.
(Courtesy Murray Resnick, MD, PhD, Brown University, Providence, RI.)
16. HISTOLOGY
Histology demonstrates marked fibrotic thickening of the endocardium (arrow), with
proliferation of fibrous tissue in the underlying myocardium, which is consistent with
endomyocardial fibrosis (Masson trichrome stain, original magnification ×50).
17. CLINICAL FEATURES
The clinical presentation of EMF depends on the chamber
involved, the location of the fibrotic lesion and its severity.
Davies described three phases of the disease in his
patients from Uganda.
The initial phase is an acute carditis phase, characterized
by febrile illness and in severe cases with heart failure and
shock.
Those who survive this acute illness, progress into a sub
acute phase followed by a chronic phase.
Most of the patients come to clinical attention in this
chronic burnt-out phase
18. Right Ventricular Endomyocardial Fibrosis
In pure or predominant right ventricular involvement, the
right ventricular apex is characterized by fibrous
obliteration, which may extend to involve the supporting
structures of the tricuspid valve, with ensuing tricuspid
regurgitation.
Patients exhibit an elevated JVP, a prominent v wave with
rapid y descent, and a right-sided S3 gallop.
There is prominent hepatomegaly with a pulsatile liver,
ascites, splenomegaly, and peripheral edema, but
pulmonary congestion is typically absent because of the
lack of left-sided involvement.
19. Left Ventricular Endomyocardial Fibrosis
In cases of predominant left-sided disease, fibrosis involves
the ventricular apex and often the chordae tendineae or the
posterior mitral valve leaflet, producing mitral
regurgitation.
The associated murmur may be late systolic, characteristic
of a papillary muscle dysfunction murmur, or pansystolic.
Findings of pulmonary hypertension may be prominent,
and an S3protodiastolic gallop is frequently present.
20. Biventricular Endomyocardial Fibrosis
Biventricular EMF is more common then either isolated
right- or left-sided disease.
The typical clinical presentation of EMF resembles right
ventricular EMF; however, a murmur of mitral
regurgitation is indicative of left-sided involvement.
Unless left ventricular involvement is extensive, severe
pulmonary hypertension is absent and the right-sided
findings are the predominant mode of presentation.
Approximately 15% of patients will experience systemic
embolization, and only 2% will have infective endocarditis.
21.
22. In a study conducted in india which included 145 pts with EMF
show clinical profile
The mean (SD) age of the patients at first presentation was 26±3
(14±1) years for women (n = 70) and 21±1 (11±9) years for men (n
= 75); 33.1% were under 15.
Gupta PN, Valiathan MS, Balakrishnan KG,
Kartha CC, Ghosh MK. Clinical course of
endomyocardial fibrosis. Br Heart
J. 1989;62:450–4.
Sree
Chitra Tirunal Institute for Medical
Sciences and Technology,
Trivandrum 69501 1, Kerala, Indi
23. A COMPARISON OF THE CLINICAL AND CARDIOLOGICAL
FEATURES OF ENDOMYOCARDIAL DISEASE IN
TEMPERATE AND TROPICAL REGIONS
J. DAVIES ,G. VIJAYARAGHAVAN et al A comparison of the clinical and cardiological
features of endomyocardial disease in
temperate and tropical regions,1983.
24. J. DAVIES ,G. VIJAYARAGHAVAN et al A comparison of the
clinical and cardiological features of endomyocardial disease in
temperate and tropical regions,1983.
25. RV EMF
Right atrial (RA) abnormality - peaking and increased P wave
amplitude in lead II
Tharakan J. Electrocardiogram in endomyocardial fibrosis. Indian J
Pacing Electrophysiol.2011;11:129–33
ECG
DIAGNOSIS
26. QR pattern with a diminutive R wave in lead V1 , attributed to RA
enlargement, though this pattern is seen even in patients with atrial
fibrillation (AF) .
Tharakan J. Electrocardiogram in endomyocardial fibrosis. Indian J
Pacing Electrophysiol.2011;11:129–33
27. In isolated RV EMF - A dominant R wave in V2 in the absence of QR
pattern in V1 in 14 of 25 patients resulting in early transition from a
dominant S wave in right sided chest leads to dominant R wave in V2 or
earlier .
Tharakan J. Electrocardiogram in endomyocardial fibrosis. Indian J
Pacing Electrophysiol.2011;11:129–33
28. AF is seen in the end stage patients with advanced
RV EMF.
It is noteworthy that patients with RV EMF and AF
rarely have fast ventricular response, in striking
contrast to patients with AF and LV EMF.
Patients with large pericardial effusion often have
low voltage QRS, satisfying the low voltage ECG
criteria.
29. LV EMF
LA abnormality.
AF occurs in advanced and uncorrected case of LVEMF.
The odd finding is a uniform ST segment depression and T
wave inversion more evident in the lateral chest leads,
similar to apical hypertrophic cardiomyopathy (HCM) and
non- ST elevation acute coronary syndromes
31. More than 50% patients with EMF have biventricular
involvement
The ECG reflects a combination of these abnormalities.
ECG findings reported by Balakrishnan et al from Sree
Chitra Tirunal Institute for Medical Sciences and
Technology, Trivandrum - 210 patients
AF (33%), junctional rhythm or heart block (4.4%), right
axis deviation (29%), intra ventricular conduction
abnormality (16%) and atrial tachycardia or atrial
flutter(3.5%).
Balakrishnan KG, et al. Clinical course of patients in Kerala. In: Valiathan MS,
editor.Endomyocardial fibrosis. Oxford University Press; 1993
32. Earlier three large studies of 60 patients, 95 patients
and 50 patients, reported AF in 40%, junctional
rhythm in 2%, RA enlargement in 32% and QR pattern
in V1 in 25% patients .
LA enlargement was common in patients with LVEMF
and 18% of LVEMF patients had LVH (left ventricular
hypertrophy) with strain .
Sapru RP. Clinical profile of endomyocardial fibrosis. In: Sapru RP,
editor. Endomyocardial fibrosis in India. ICMR; 1983.
Vijayaraghavan G, et al. Endomyocardial fibrosis: Clinical, ECG and
radiological features. In: Sapru RP, editor. Endomyocardial fibrosis in
India. ICMR; 1983.
Jacob G, et al. Endomyocardial fibrosis in Kerala. In: Sapru RP,
editor. Endomyocardial fibrosis in India. ICMR; 1983.
Jacob G, et al. Endomyocardial fibrosis in Kerala. In: Sapru RP,
editor. Endomyocardial fibrosis in India. ICMR; 1983
33. Echocardiography
Apical fibrosis of the right ventricle (RV), left ventricle (LV), or
both ventricles.
Tethering the atrioventricular (AV) valve papillary muscles,
leading to mitral and/or tricuspid regurgitation
Giant atrial enlargement .
Restrictive filling pattern on Doppler recordings of mitral valve
inflow .
Apical thrombi are often present
34.
35.
36.
37.
38.
39. In a study conducted in brazil - 12 pts with EMF were studied
with Doppler echocardiography with the purpose of describing
the echocardiographic features and identify the affected sites.
The average age was 41 years (range 16 to 59 years), 2 men and 10
women.
3 (25%) had isolated right ventricular involvement, one patient
(8%) left ventricular, 8 patients (66%) both ventricular.
Doppler echocardiographic findings were: right atrium
enlargement (91%), right ventricle outflow dilatation (83%),
paradoxical septal motion (83%), left atrial enlargement (33%),
mitral and tricuspid valve prolapse (50%), pericardial effusion
(41%), mitral regurgitation (75%), tricuspid regurgitation
(100%), apex obliteration (50%) and a restrictive type flow
pattern (50%).
Tello r Cuan et al . Doppler echocardiography in endomyocardial fibrosis
, Brazil ,1994.
40. In a study conducted in india which included 145 pts
with EMF ,Echocardiographic data were available in
86 patients.
The mean (SD) left ventricular internal dimensions
in diastole and systole were 4.17 (1.19) cm and 2.9 (1.
07) cm respectively.
Pericardial effusion was present in 35 (40.7%),
intracavitary thrombi in 11 (12.8%), and myocardial
calcification in 16 (18. 6%) patients.
Gupta PN, Valiathan MS, Balakrishnan KG, Kartha CC, Ghosh MK. Clinical
course of endomyocardial fibrosis. Br Heart J. 1989;62:450–4. Sree
Chitra Tirunal Institute for Medical Sciences and Technology,
Trivandrum 69501 1, Kerala, India
41. An echocardiographic screening study in Mozambique
included echocardiographic criteria for the diagnosis and
staging of EMF
As the natural history of EMF is not well defined, these
criteria will likely aid in defining the stages of this disease
and in determining the clinical significance of early EMF.
42. Classification of Endomyocardial
Fibrosis
They defined major and minor criteria for the diagnosis of EMF
on the basis of features of advanced disease and pathologic
features of early stages described in postmortem studies.
Endomyocardial fibrosis was diagnosed in the presence of two
major criteria or one major criterion associated with two minor
criteria
Possible scores ranged from 0 to 35; cases with
scores of 8 or less were classified as mild,
scores of 8 to 15 as moderate,
scores of 15 or more as severe.
43. A Population Study of Endomyocardial Fibrosis in a Rural Area of Mozambique Ana Olga Mocumbi, M.D.,
Maria Beatriz Ferreira, M.D., Ph.D., Daniel Sidi, M.D., Ph.D., and Magdi H. Yacoub, F.R.S. N Engl J Med
2008;359:43-9.
44. HEMODYNAMIC FINDINGS
The typical haemodynamic finding on cardiac
catheterization is the dip and plateau pattern of
restrictive ventricular filling.
45. In a study conducted in
Mozambique included 21
pts showed
In patients with RV EMF,
RA pressure was increased
with prominent A waves,
which was also seen in the
right ventricular and
pulmonary artery pressure
tracings .
The right ventricular
pressure tracing showed a
dip and high end-diastolic
pressure 5 mm Hg higher
than the pulmonary
diastolic pressure, and the
contour of the right
ventricular pressure
tracing was distorted .
46. In patients with left
sided involvement, left
ventricular end-
diastolic pressure was
very high.
A dip and plateau
pattern of the
ventricular pressure
curve present .
Pulmonary
hypertension present
in all patients with left
and biventricular EMF
47.
48.
49.
50. In a study conducted which included 8 pts, their
hemodynamics showed
Vijayaraghavan G, Cherian G, Krishnaswami S, Sukumar IP. Left
ventricular endomyocardial fibrosis in India. Br Heart J. 1977;39:563–8
51. Gupta PN, Valiathan MS, Balakrishnan KG, Kartha CC, Ghosh MK. Clinical
course of endomyocardial fibrosis. Br Heart J. 1989;62:450–4. Sree
Chitra Tirunal Institute for Medical Sciences and Technology,
Trivandrum 69501 1, Kerala, India
52. Chest X-Ray
Cardiomegaly - varying degrees from mild to severe.
Right atrial enlargement in the patients with right-sided
involvement, left atrial enlargement in patients with left-
sided involvement, and biatrial enlargement in those with
biventricular involvement.
Pulmonary venous congestion with left-sided involvement.
Endocardial calcification
53.
54. Somers K, Williams AW. Intracardiac calcification in endomyocardial
fibrosis. Br Heart J.1962;24:324–8
55. Vijayaraghavan G, Cherian G, Krishnaswami S, Sukumar IP. Left ventricular
endomyocardial fibrosis in India. Br Heart J. 1977;39:563–8
56.
57.
58. ANGIOGRAPHY
CHARACTERISTIC OBLITERATION OF THE APEX OF THE INVOLVED VENTRICLE(S)
WITH VARYING DEGREE OF AV VALVE REGURGITATION
Left ventricular angiogram in the RAO view showing obliteration of the apex
(arrow) in systole (top, a) and diastole (bottom, b).
Walid M. Hassan, MD, FCCP; Mohamed et al Pitfalls in Diagnosis and Clinical, Echocardiographic, and
Hemodynamic Findings in Endomyocardial Fibrosis A 25-Year Experience 2005
59. Right ventricular angiogram in the RAO view in a patient with right-sided EMF
showing complete obliteration of the apex of the right ventricle, dilated right
atrium, and severe TR. .
Walid M. Hassan, MD, FCCP; Mohamed et al Pitfalls in Diagnosis and Clinical, Echocardiographic, and
Hemodynamic Findings in Endomyocardial Fibrosis A 25-Year Experience 2005
60.
61. CMR imaging with
contrast demonstrates
myocardial fibrosis.
In early disease where
there is suspicion for
active inflammation, CMR
may be useful in
identifying patients who
may benefit from steroid
therapy
Cardiovascular magnetic resonance imaging
63. Endomyocardial Biopsy
Photomicrograph of endomyocardial biopsy specimen
showing marked thickening of the endocardium (E) with fibrosis
(hematoxylin-eosin, original × 200).
64. MANAGEMENT
Medical therapy
Remains challenging.
One third to one half of patients with advanced disease die
within 2 years
Atrial fibrillation is a poor prognostic indicator, although
symptomatic relief can be achieved with rate control
Heart failure - difficult to control, and diuretics are effective only
in early stages of disease, losing efficacy with advanced ascites.
65. Surgery
Endomyocardial resection - endocardectomy with valve
replacement or repair - especially in subjects in advanced heart
failure
Immediate postoperative mortality is high - 15 to 30 %.
A surgical series of 83 patients from Brazil all in NYHA class
grade III to IV, and with a mean follow-up of 7.6 years had a
survival probability at 17 years of 55 percent .
4 (5.8%) patients - recurrence of the fibrosis and were reoperated on
and in 6 (8.8%), EMF appeared in the other ventricle.
5 (7.3%) patients were reoperated on to replace either a valve prosthesis
or a native valve which had been preserved during the first procedure.
Only 24 (45%) of the 53 surviving patients are in functional class I or II.
Fernando Moraes , Cleuza et al Surgery for endomyocardial fibrosis
revisited September 1998
66. Published series have been small, overall experience
is limited, and questions remain about the
appropriate timing, peri-operative mortality, and
long-term prognosis .
67. Left ventricular angiogram in the RAO view showing a small left ventricle
with apical obliteration,severe MR, and dilated left atrium in a patient with
left-sided EMF (top, a) and after surgery with endocardectomy
and mitral valve replacement (bottom, b).
Fernando Moraes , Cleuza et al Surgery for endomyocardial fibrosis
revisited September 1998
68. CLINICAL COURSE
The factors significantly affecting survival were
Gupta PN, Valiathan MS, Balakrishnan KG, Kartha CC, Ghosh MK. Clinical
course of endomyocardial fibrosis. Br Heart J. 1989;62:450–4. Sree
Chitra Tirunal Institute for Medical Sciences and Technology,
Trivandrum 69501 1, Kerala, India
69. Gupta PN, Valiathan MS, Balakrishnan KG, Kartha CC, Ghosh MK. Clinical course of
endomyocardial fibrosis. Br Heart J. 1989;62:450–4. Sree
Chitra Tirunal Institute for Medical Sciences and Technology,
Trivandrum 69501 1, Kerala, India
70. Changing natural history of endomyocardial fibrosis
Gupta and colleagues defined the natural history of the
disease in Kerala in the late 1980s.
Follow up of the initial 200 patients showed a 10 year
survival of only 37 %.
Ascites, atrial fibrillation and NYHA class IV were the poor
prognostic indicators.
71. Eighty nine patients, who underwent endocardiectomy
with MVR had an actuarial survival of 55 % during the
same period.
Significant decline in the number of new cases happened
in the hospital admissions in Kerala in the subsequent
decades.
Natural history in them was more favourable with less than
10 per cent mortality on seven years follow up.
The average number of cases seen declined by half in the
last decade, compared to the previous decade.
72. The mean age of the patients seen is now 33 yr compared to
25 yr in the previous decade, suggesting that people who
were asymptomatic in the previous era are now being
picked up on evaluation.
There are no patients below 10 yr, whereas in the previous
decade, 28 per cent were below the age of 15 yr.
The patients are less symptomatic and older.
The majority are incidentally diagnosed when evaluated for
electrocardiographic or echocardiographic abnormalities.
73. Temporal correlates of this changing natural history are worth
analyzing.
The period noted in the natural history studies belong to the 30 year
period of 1976 to 2007
Kerala witnessed substantial economic, nutritional and health
transitions.
Cassava and plantain are no longer the staple diet for the Keralites.
The per capita calorie consumption increased from 1600 to 2100 Kcals.
The nutritional deficiency disorders were replaced by those of over
nutrition and currently, Kerala is the diabetic capital for India.
Thanks to the good female literacy, health status of Kerala is acclaimed
as an example for good health at low cost.
74. A community survey shows that there is a substantial decline in
worm load per child.
Filarial endemicity continues to be little less, with rigorous
governmental programmes initiated for its control.
Eosinophilia in children is now uncommon.
There is substantial decline in rheumatic fever and rheumatic
heart disease in children of Kerala correlating with the improved
health care services and quality of life.
The question which needs to be answered now is what really
caused this decline; is it the change in living standards, or
change in the dietary pattern or the reduction in childhood
infections? By and large, endomyocardial fibrosis could be a
reaction pattern of the endocardium to a variety of insults
75. Presence of interstitial fibrosis, myohypertrophy, and calcification
speaks of the role of cytokines in its genesis.
Predominant right ventricular involvement in children could indicate
an insult when the right ventricle could be more susceptible.
Right ventricle receives most of the umbilical venous return in utero
and is more dominant.
But no antenatal cases are reported till date and the youngest report is
that of a 4 month old baby.
The inflammatory response occurring in the younger age group could
manifest as calcification in later years.
Whether this calcification has its similarity to vascular and valvar
calcium occurring in older age group; if so, could it be the factor which
holds the key for unraveling this mystery?
76. SUMMARY
EMF is a restrictive cardiomyopathy observed in the tropics usually at
the end-stage of the disease.
It may be indistinguishable from Loeffler’s endocarditis, observed in
temperate climates.
The pathogenesis remains unknown; however, eosinophilia may play a
role.
Echocardiography may show uni- or bilateral ventricular apex
obliteration with severely dilated atria and a restrictive filling pattern.
The prognosis is poor, with a mortality estimated at 25 % per year.
Surgical treatment with endomyocardial resection and valve
replacement may be beneficial in patients with advanced apical
obliteration and sever heart failure symptoms.
Editor's Notes
1946: Bedford and Konstam described a form of heart disease in 40 West African soldiers . Several of these patients died
1946: Davies JN first coined the term endomyocardial fibrosis (EMF) while working in Uganda and said that “he became convinced rightly or wrongly that he had met a new disease”.
He also discussed the initial clinical description of the disease by Bedford and Constam in 1946.
1938 : Arthur Williams, the foundation professor of medicine at Makerere University, Kampala, Uganda had described two cases of mitral incompetence and correlated with large patches of fibrosis affecting the ventricular walls at necropsy and this is perhaps the earliest documentation of EMF in literature
Importantly, it is also recognized in the Middle East, particularly Saudi Arabia.[79] Cardiac dysfunction occurs because of fibrous lesions that affect the inflow of the right and left ventricles and that may also involve the atrioventricular valves, thereby producing regurgitant lesions.
The cause of the underlying fibrotic process of EMF is largely unknown; however, several theories exist and are briefly reviewed
In support of the eosinophilia theory is the observation that EMF resembles a late stage of Loeffler's endocarditis (eosinophilic myocarditis) (picture 1), a process known to result from sustained eosinophilia in patients with hypereosinophilic syndrome [12,13]. EMF and intraventricular thrombosis have also been observed following a variety of other eosinophilic syndromes including hypersensitivity myocarditis [14], parasitic infections [12,13], eosinophilic leukemia, sarcoma, carcinoma, and lymphoma [15], GM-CSF administration [16], and prolonged drug-induced eosinophilia
Several infections have been implicated in the pathophysiology of EMF, including toxoplasmosis [20], rheumatic fever [21], malaria [22], and helminthic parasites [4,23]. A consistent association with one organism, however, has not been demonstrated. For example, mice infected with plasmodium berghei develop EMF lesions [24], but a study of a series of 47 African children aged 5 to 15 years old with severe and complicated plasmodium falciparum infection produced insufficient evidence to link these two diseases [25]. Also opposing the infectious hypothesis is the observation that there are many tropical countries with similar burdens of malaria and filariasis as Uganda and Nigeria that do not have reported cases of EMF
There is often a pericardial effusion, which may be large.
The right-sided heart border may be indented because of apical scarring.
Presenting as a thick layer of collagen overlying loosely arranged connective tissue.[79]
In addition, there are fibrous and granular septations extending into the underlying myocardial tissue.
Myocyte hypertrophy is common.[52]
Whereas cellular infiltration is uncommon, interstitial edema is frequently present.
Fibroelastosis that is found in the ventricular outflow tracts beneath the semilunar valves often represents a secondary process caused by local trauma.
Examination of intramural coronary arteries may show involvement with medial degeneration, the deposition of fibrin, and fibrosis.
The early part of the disease is rarely clinically recognized in India and the disease comes to attention in the late stages and isolated endocardial involvement and intracardiac thrombi are the peculiar features.
In this regard, pulmonary artery and pulmonary capillary wedge pressures are normal.
A large pericardial effusion is often present.
The right atrium may be enormously dilated.
The electrocardiogram often has findings consistent with right-sided enlargement, especially a qR pattern in lead V1, and supraventricular arrhythmias are common.
The chest radiograph often demonstrates obvious right atrial prominence, a pericardial effusion, and calcification in the walls of the right and, less frequently, the left ventricle.
Echocardiography demonstrates thickening of the right ventricle with obliteration of the apex, a dilated atrium, hyperechoic endocardial surfaces, and abnormal septal motion in patients with tricuspid regurgitation.
On angiography, the right ventricular apex is typically not visualized because of fibrous obliteration; tricuspid regurgitation, right atrial enlargement, and filling defects in the right atrium caused by thrombi may be present.
The electrocardiogram usually shows ST-segment and T wave abnormalities, low-voltage QRS complexes if a pericardial effusion is present, or left ventricular hypertrophy.
Left atrial abnormality is often noted.
As with right-sided involvement, atrial fibrillation is often present and portends a poor prognosis.
Echocardiography reveals increased endocardial echoreflectivity, preserved systolic function, apical obliteration, enlarged atrium, pericardial effusion of varying size, and Doppler ultrasound evidence of mitral regurgitation.
Pulmonary hypertension is typically observed during cardiac catheterization, as well as left atrial hypertension and a reduced cardiac index.
Left ventriculography shows mitral regurgitation, and ventricular filling defects caused by intracavitary thrombi may be present.
Coronary arteriography usually excludes obstructive epicardial vessel stenoses.
The ECG often suggests right atrial (RA) abnormality, reflecting RA pressure and volume overload . ECG abnormality includes peaking and increased P wave amplitude in lead II and rarely tall peaked and narrow positive P waves resembling the Himalayan P waves of Ebstein's anomaly.
Left atrial (LA) abnormality in ECG parallels the diastolic dysfunction and degree of mitral incompetence.
AF occurs in advanced and uncorrected case of LVEMF.
The odd finding is a uniform ST segment depression and T wave inversion more evident in the lateral chest leads, similar to apical hypertrophic cardiomyopathy (HCM) and non- ST elevation acute coronary syndromes
Not uncommonly, nonspecific ST T wave abnormalities in the precordial leads in a routine ECG evaluation brings these patients to clinical attention for further evaluation to exclude coronary heart disease and LVEMF is diagnosed during echocardiographic study or LV angiogram.
Although clinically similar to Loffler’s endocarditis, the diagnosis of endomyocardial fibrosis (EMF) should be reserved for patients from endemic regions without a clearly identified cause for sustained eosinophilia with the classic echocardiography features listed below :
(image 3). In EMF, the apex maintains inward systolic contractile motion that may help to differentiate EMF from other causes of apical thrombi associated with an akinetic or dyskinetic apex such as myocardial infarction or Chagas disease [42] (figure 1).
Doppler echocardiography is a useful method for the diagnosis of endomyocardial fibrosis, the finding of normal or small ventricles associated with apex obliteration and enlarged atria, mitral or tricuspid regurgitation and a restrictive type flow pattern are characteristics of this disease. In our population, the isolated or predominantely right ventricular involvement is the most common finding as it represented 83% of the cases.
patients had markedly elevated ventricular filling pressures with characteristic
restrictive hemodynamic pattern.
Table 1 summarises the right and left heart catheterisation
data.
Calcification in endomyocardial fibrosis, as known in Uganda, has hitherto only been recognized at necropsy (Davies and Ball, 1955).
In advanced cases of constrictive endocardial fibrosis, calcium deposition occurs in areas of extensive fibrosis particularly at the right ventricular apex.
X-ray chest in an advanced case of right ventricular endomyocardial fibrosis often shows gross enlargement of the cardiac silhouette, predominantly contributed by the right atrial enlargement. But it can also be partly due to associated pericardial effusion as in this case. Varying degrees of pericardial effusion is a common association of severe right ventricular endomyocadial fibrosis with systemic venous congestion and anasarca.
Features of pulmonary arterial hypertension in endomyocardial fibrosis (EMF) could be either due to left ventricular involvement and consequent elevation of left atrial and pulmonary venous pressures or due to pulmonary embolism from a right atrial thrombus as demonstrated earlier.
Angiography
characteristic obliteration of the apex of the involved ventricle(s) with varying degree of AV valve regurgitation in all patients with left ventricular
or biventricular EMF (Fig 4). MR was severe in six
patients (cases 2, 4, 16, 17, 18, and 21) [Fig 5] and
mild to moderate in five patients (cases 1, 12, 13, 19,
and 20). In patients with right ventricular involvement,
there was obliteration of the right ventricular
apex with dilation of the outflow tract. In one patient
(case 7), there was exceptional involvement of the
right ventricular inflow and outflow with obliteration
of the apex (Fig 6). TR was severe in 5 patients and
mild to moderate in 12 patients. Obliteration of both
ventricular apices was observed in biventricular
EMF. The contractility of the remaining parts of the
ventricle varied from normal to severely impaired.
Coronary angiographies were normal in all patients.
Presently, cardiac MRI is a mainstay in the evaluation of the myocardium thickness and function, as well as the LV perfusion, allowing the assessment of the myocardial enhancement, which is a relevant factor in the diagnosis of several cardiac diseases.
Nine specimens were obtained (done during our
early experience with the disease), and seven specimens
showed features of EMF, namely fibrous
thickening of the endocardium, made up of collagen without elastic fibers (Fig 7). A few fibrocytes and an
organized thrombus were seen in four specimens
(See "Natural history and therapy of myocarditis in adults", section on 'Eosinophilic myocarditis'.
. (See "Treatment and prognosis of diastolic heart failure" and "Definition and classification of the cardiomyopathies", section on 'Restrictive cardiomyopathy'.)
The factors significantly affecting survival were
considerable anaemia (haemoglobin < 100 g/l),
development of embolic episodes, QRS axis more
than + 90', delayed intraventricular conduction
(QRS duration > 0 12 s), New York Heart Association
classes III and IV, a short symptomatic history
before admission to hospital, the presence of cyanosis,
and left and/or right ventricular failure at first presentation (table 4). The analysis showed that age,
sex, and predominantly right or left ventricular
endomyocardial involvement had no effect on
survival.