Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. - What is the significance of measuring CRP to assess heart disease risks? - CRP is the classical acute phase protein. It's the first protein in the plasma, that was discovered way back in 1929 and a few years after that, to behave as an acute phase protein. This means that if you have any tissue damage, infection, almost any sort of pathology, which damages the body, more CRP is produced, and as a result, the CRP concentration in the plasma increases. And subsequently many other proteins have been found to behave in that way. But CRP is almost uniquely dynamic, so it increases from very low concentration, it can go up by ten thousand fold in concentration in response to an acute injury or an acute infection, and there's only one other protein which behaves with similar dynamism, and that's called "serum amyloid A" protein, a it's a completely unrelated protein, but of interest to us, because it can make amyloid, which we've been talking about before. But putting that aside, CRP is uniquely useful in clinical medicine as a marker of this acute phase response. And there are several things that have to be understood about CRP. The first is, it is completely non-specific. So the CRP can never be diagnostic of any particular condition, you can only interpret the CRP concentration in the context of knowing everything about the patient: the patient's history, all their demography, what diseases they've got, what treatments there are on... Only then can you you interpret the CRP value. But if you have all that information, the CRP is immensely useful, It tells you whether patients have got some genuine tissue-damaging pathology or not. So it's a screening test for organic disease and it tells you, if a patient has got a particular disease, whether it's getting better or worse, whether your treatment is working or not working, and lastly there are a few diseases, quite serious diseases, where the CRP doesn't increase, very surprisingly, unlike nearly everything else, where the CRP does not increase. But in those people, if they get an infection, bacterial or viral infection, then the CRP increases - so it's a good test for and intercurrent infection, in that rare group of diseases, where the CRP doesn't go up with the disease on its own. So we come back to these three indications for measuring CRP - Patient comes the doctor: "I've got terrible pain in my chest and I feel breathless". You measure the CRP - it's normal. You have excluded heart attack, pulmonary embolism, pneumothorax, broken ribs - a lot of these things you can diagnose just by examining the patient - [AT] it narrows diagnostic options down... Most of those things you can diagnose clinically, you know if a patient has a broken rib or not... So, on one hand you can exclude things, and have a different approach to investigating that patient, and counseling them, and on the other hand if it's high, if the CRP is raised, it doesn't tell you what the diagnosis is - but it tells you "there's something serious going on with this patient" and we have to investigate. Dr. Anton Titov MD
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Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. Over the last 40 years you have been on the discovery path of a particular method to treat amyloidosis. Could you please describe in more detail your approach to amyloidosis treatment? What is the essence of the discovery that you have made? Well, my approach to any sort of treatment, devising new treatment for the disease, is firstly to try and understand what the pathobiology is, what is the underlying abnormality in the biology, the functioning of the person who's become ill with this particular disease. So in the first place I've been studying for many years, what are the processes involved in amyloid formation? Why do these proteins misbehave in the way that they do? What are the properties of the amyloid once it is formed? How does it damage the tissue? And we came to a conclusion that possibly one of the reasons why the body doesn't clear away amyloid fibers is because there's always another protein associated with them. So, as I said before, there are about 30 different molecules, different proteins that can form amyloid fibrils in the body, and we see them in different types of amyloidosis. But regardless of the protein that makes the amyloid fibrils there's always another protein that is bound to the protein fibrils, and that protein is called "serum amyloid P component" "SAP" for short, and before I started working in the field it was known that this protein was present in all amyloid deposits that had been looked at, but nobody knew why it was there or what it was doing there. And my first interest in amyloid was aroused by my discovery that the protein, SAP, was a protein which could bind to amyloid fibrils and, indeed, to a number of other things in a calcium-dependent way. Calcium is a mineral, obviously, which everybody has in their blood, and you have to have it in order to be alive, and so inside the body and outside the cells, there's always calcium, there's always a reasonably abundant amount of calcium, and in the presence of this calcium, SAP binds to all amyloid fibrils. If amyloid fibrils form anywhere in the human body, they always have SAP coating them. So I was intrigued from the outset by the fact that all amyloid deposits contain this protein, something which is always present is either an amazing epiphenomenon or it's got something to do with the disease. So I have been pursuing that idea for a number of years and we gradually accumulated a convincing body of evidence that indeed the SAP binding to amyloid fibrils contributes to both their formation and their persistence. We developed a lot of this evidence, other people have got corroborative evidence, and so in the 1980s I first had the idea of trying to separate the SAP from amyloid deposits, and we discovered for the first time a small molecule, which could dissociate in vitro SAP from amyloid deposits in organs of people who died. We homogenize these organs with our small chemical and separate these two components, and I wrote a paper suggesting this as a possible therapeutic approach, and then I visited all the major pharmaceutical companies in the world and said "I've got a new idea for the possible treatment of amyloidosis" and they said to me "What is amyloidosis?" It was a rare disease and nobody was very interested in it. Dr. Anton Titov MD
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Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. Professor Pepys, you are a world leader in amyloidosis research and treatment. What is amyloidosis? - Amyloidosis is a disease caused by the deposition of abnormal insoluble protein fibers in the extracellular space in various tissues and organs. There are many different forms of amyloidosis, characterized by different proteins, which form these fibrils. Regardless of the protein type that makes the fibrils, however, the fibrils eventually look very similar histologically, morphologically, and by various imaging techniques, and they have similar effects in that they distort the structure and therefore the function of whatever tissue is involved. Amyloidosis is a rare condition, probably responsible for the deaths of about one in a thousand people in developed countries, so it's rare but not vanishingly rare, and it's clinically very important, because untreated it is always fatal, and even with the best treatment currently available it's still fatal in nearly everybody who gets it, although survival is now much better than it was in the past. A major problem in the clinical recognition of amyloidosis and in its diagnosis is that the disease is sufficiently rare that many doctors haven't seen probably any cases or maybe only a few cases in their whole clinical career. And the other problem is that the disease can present in almost any way at all, since in systemic amyloidosis - the form that can affect any tissue throughout the body, except the brain substance itself. it can present clinically with manifestations in any tissue or any organ, and therefore people don't think of it. So patients can present with heart failure, or kidney failure, or problems with their nerves, or their skin or their liver or their spleen. Any part of the body can be involved, and can be the main part that's involved, and on the whole clinicians unfamiliar with the disease don't think of it, therefore don't do the right tests to diagnose it and don't recognize it. So sadly, a very common experience that we have is that patients are diagnosed relatively late in the disease, often after several years of being ill, being investigated by doctors sometimes in many different hospitals, before somebody thinks of it or by accident the diagnosis is made. And sadly that means that by the time they come to us, who are experts in recognizing and treating the condition, it may be too late. So even now, about a quarter of the patients with the commonest form of systemic amyloidosis, which is called AL amyloidosis, they still die within the first six months after being diagnosed, regardless of all the advances that there have been in treatment. So it's still a very major and serious unmet medical need. - And part of the reason why there is just 6 months survival after diagnosis is the time lag before the correct diagnosis and possible initiation of therapy patients go around and around to various doctors - Patients live for such a short time after the diagnosis is made, because they already have irreversible damage to the organs, particularly the heart, but also sometimes the kidneys and other organs, and it may be difficult or impossible to salvage those failed organs. So that is a major problem. Dr. Anton Titov MD
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Shortness of breath? Learn more and get a better lung disease treatment plan with top experts. Visit our Online Expert Centers at https://diagnosticdetectives.com/expert-centers/ Exclusive interview / Dr. Anton Titov MD and Professor Dr. Aaron Waxman MD, leading pulmonary arterial hypertension, right heart failure and lung disease expert. Find out exact cause if you have shortness of breath - get a precise diagnosis and best treatment for shortness of breath root cause. - Is there a clinical case you could discuss that could illustrate some of the lung disease topics that we discussed? - There are a whole host of clinical cases. I think some of the the things that come to mind: we have obviously a whole degree of patients who present [with symptoms of lung disease]. And when I think of some of our patients who have presented with very advanced lung disease, there we're using multi-modality treatments. So these are patients who generally have idiopathic pulmonary arterial hypertension, who present in right heart failure, who we start on aggressive therapy with intravenous prostacyclins as well as combination therapy with endothelin antagonists and PDE5 inhibitors. But that's the limits of our ability there. We've worked with companies to develop novel treatment approaches, including fully implantable drug delivery systems that we're waiting for FDA approval on at this time. But we've been able to get rid of Hickman catheters that way, and put everything inside the body, so that we limit the infection risk and a complication risk with the drug delivery systems. We've also been able in those patients to think outside the box and use targeted therapy, like anti-inflammatory immunosuppressive therapies in low doses that might actually help reverse some of the abnormal pathway functions that are driving [lung blood vessel] remodeling. An example is using a drug like tacrolimus, which is normally used for transplantation and immunosuppression, whereas in low doses we have evidence, in working with collaborators at Stanford, that tacrolimus may actually reverse some of the genetic abnormality that is acquired in PAH lung disease. So we've been treating some of our more advanced patients with tacrolimus. There's also targeted therapy that we've been able to use in these patients that targets mitochondrial function. Because we've learned in all of these patients that there is dysfunction and really an inefficient approach to metabolism whereas they tend to shift to glycolysis rather than oxidative phosphorylation. So using different medications that we know might do the reversal of that, we have started treating some of these patients. And a nice thing is that patients have responded well to these interventions. It's very interesting because you showed that there is a mitochondrial dysfunction [in lung diseases]. The mitochondria are the sort of energy-generating power stations of the cell. It could explain some of the shortness of breath that the patients with lung disease are experiencing. Yes, mitochondria. When I think about medicine, and as an intensivist, when I think about critical care, and patients who come in with severe disease like septic shock or whatever kind of shock you want to address, it's probably ultimately the mitochondria that are getting damaged or become dysfunctional or become hibernating. And if we have targeted therapies that can get into the cell, get into that mitochondria and regenerate it, then we will probably change how we care for patients. One of the goals when we started our stem stem cell studies is that when we see patients in heart failure, there's a clear shift in metabolism to glycolysis from oxidative phosphorylation in the myocardium. And we thought that because of data from in vitro studies, where if you take stem cells and you mix them with diseased cells, stem cells and diseased cells can fuse and transfer mitochondria and restore normal bioenergetics. We thought, why can't we do that in the living heart?
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Shortness of breath? Learn more and get a better lung disease treatment plan with top experts. Visit our Online Expert Centers at https://diagnosticdetectives.com/expert-centers/ Exclusive interview / Dr. Anton Titov MD and Professor Dr. Aaron Waxman MD, leading pulmonary arterial hypertension, right heart failure and lung disease expert. Find out exact cause if you have shortness of breath - get a precise diagnosis and best treatment for shortness of breath root cause. - Pulmonary arterial hypertension treatment. You mentioned phosphodiesterase type 5 inhibitors. They are also used for erectile disfunction. Common medications are viagra, sildenafil, and there are other medications of that class. So they're also used to treat pulmonary arterial hypertension. What is a typical way how they are used for pulmonary arterial hypertension? Are they effective? There is probably a different dosing schedule of those medications? So phosphodiesterase 5 inhibitors are in the nitric oxide pathway. And nitric oxide response, which really is our most potent vasodilator, works through cyclic GMP. So all the phosphodiesterase 5 inhibitors do is keep that cyclic GMP around longer by preventing its breakdown. And within the same path now we also have a medication called Riociguat, which is a soluble guanylate cyclase stimulator. So it actually increases the amount of available cyclic GMP and works in parallel with nitric oxide or independently of nitric oxide in pulmonary arterial hypertension. These patients generally have inadequate NO production. So all of these drugs are vasodilators. There's probably some added benefit, although we don't fully understand yet how, as far as remodeling - both myocardial remodeling and vascular remodeling. But there's no way to know which patients are going to get the most benefit from each individual drug. But I would say from an efficacy standpoint they're all pretty equivalent in pulmonary arterial hypertension. We don't combine them, but as individual drugs they're all pretty equivalent. - Are they used early in a therapy of pulmonary arterial hypertension, or when the first line therapy fails? - No, they probably are now first line therapy. Certainly sildenafil and tadalafil are considered first-line therapy, because they're generally very well tolerated and they're easy to use and they've been around for a long time in pulmonary arterial hypertension. I think Riociguatis a little more complicated to use because there's titration involved and it has a little more broader FDA approval targeting. It includes chronic thromboembolic disease but otherwise it's probably equally effective in pulmonary arterial hypertension. - Is the typical dosage [of PDE5 inhibitors in PAH] continuous or daily? Is it a smaller dose to compare with doses used for erectile disfunction indications? - When we did the clinical trials in pulmonary arterial hypertension, we studied sildenafil at 20 milligrams, 40 milligrams and 80 milligrams, at 3 times per day. So the usual dose for erectile dysfunction is 25, 50 and 75 mg, and a 100 mg, "when you need it". So certainly during the clinical trial, before the drug was approved, we were using Viagra at those doses. So I think there's room for dose adjustment. The only dose that was approved was 20 milligrams three times a day. So from an insurance standpoint we might have a little difficulty changing dose. But we often do titrate the dose, and Tadalafilwe use it at 40 milligrams once a day. - Every day? So with this frequent and fairly large dosing for pulmonary arterial hypertension treatment, as far as the cardiovascular side effects or other side effects, have you seen any major side effects? It's interesting, because the reason we went to these drugs are because phosphodiesterase 5 is predominantly localized to the vessels of the lung and the vessels of the penis. So we actually don't see a huge incidence of cardiovascular side effects. There are some patients whose blood pressure may be a little soft [low] with these drugs. But most patients with pulmonary arterial hypertension tolerate it quite well. I think the most important side effect that we see is headache, and it's not a bad headache. But it can be a nuisance. But it's usually readily responsive to simple things like Tylenol and aspirin or a non-steroidal anti-inflammatory medications.
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Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. How might your drug work for the Alzheimer's disease treatment? - Alzheimer's disease is a very very different disease from systemic amyloidosis, which I have been talking about up till now. So in Alzheimer's disease there are amyloid deposits in the brain substance, which you never get with systemic amyloidosis. You can have amyloid in systemic amyloidosis in the membranes that surround the brain, and in the blood vessels, which supply the brain, but you don't actually have it within the brain substance. In Alzheimer's disease there are amyloid deposits in the brain substance, but they are microscopically small. The total amount of amyloid in the brain in Alzheimer's disease is in milligrams, a small number of milligrams, maybe a 100 milligrams, something like that. It's absolutely tiny! - In clinically manifesting people with Alzheimer's disease? - It's a very very small amount of amyloid in Alzheimer's. There are tiny microscopic plaques, they're called little amyloid deposits, which the neuropathologists call plaques, and there are other abnormal protein structures, which are called neurofibrillary tangles, which are not actually bona fide amyloid, but are very similar in terms of the way that proteins are folded, and so on. So these are the neuropathological hallmarks of Alzheimer's, but they are very very small in amount. In the liver of someone with systemic amyloidosis you might have 5 kilograms of amyloid, OK? It's a completely different situation. - 5 kilograms vs. milligrams? - Yes. So I don't call Alzheimer's disease "amyloidosis". It is very important in medicine - and this is quite a controversial area - because the neuroscientists and a lot of the biochemists and biophysicists who work in this area, who are not clinical, they use words in a very loose way. If you're a clinical doctor looking after patients, what you call things really matters. If you use the word, which is one diagnosis, and has one treatment, and you use that same word for somebody else, who has got a different disease, which requires completely different treatment, it's a disaster! So unfortunately, there is a fashion nowadays, which is probably impossible to overcome, in which this influence from the basic scientists has strayed into the clinical world to some extent, and people call Alzheimer's disease, Parkinson's disease, Huntington's disease, they call those "amyloidosis", because they all share at the molecular level certain similarity, the particular way of abnormal structures of proteins, OK? But they are not amyloidosis. In Huntington's disease the abnormal stuff is in the nucleus of the cell, in Parkinson's it's in the cytoplasm of the cell, and in Alzheimer's disease it's outside the cells, which is correct, most like amyloidosis is elsewhere. But they are completely different, they are more different than trying to do a long jump on Earth, a long jump on the Moon, and a long jump on Mars. Those are different for obvious reasons: no atmosphere, different gravity, OK? But the environment inside the nucleus, in the cytoplasm, and outside the cell is totally different, and it's very important not to conflate these things. Conflation in this way is very dangerous, and even within systemic amyloidosis, if you make a mistake and you call somebody AL amyloidosis, the treatment then is cytotoxic chemotherapy, which can kill the patient easily, and does kill patients, because it's very toxic, and if they've got a gene mutation, and do not require cytotoxic chemotherapy, to make this mistake is a disaster. So as clinicians, we are very sensitive to using words properly. - Which is very important, and I think this underscores the point of not only having a general diagnosis, "amyloidosis", "cancer of this organ", but a precise and complete diagnosis, at the molecular level. - Absolutely! Dr. Anton Titov MD
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Shortness of breath? Learn more and get a better lung disease treatment plan with top experts. Visit our Online Expert Centers at https://diagnosticdetectives.com/expert-centers/ Exclusive interview / Dr. Anton Titov MD and Professor Dr. Aaron Waxman MD, leading pulmonary arterial hypertension, right heart failure and lung disease expert. Find out exact cause if you have shortness of breath - get a precise diagnosis and best treatment for shortness of breath root cause. - What is a right heart failure? Why right heart failure attracted less attention previously? It's a cause of heart failure that is very important to determine in order to find timely and appropriate treatment? So right heart failure is really a continuum of dysfunction of the right ventricle. We think the right ventricle is part of the right heart system. And within that I think of the pulmonary vascular bed, both the pre-capillary and post-capillary pulmonary vascular bed, as well as the right atrium and the systemic veins draining into the right heart. The most common cause of right heart failure really is left heart failure. As pressures rise in the left heart, they backfill into the lung and ultimately affect the right heart. And the diseases that we focus on, the pulmonary vascular diseases, where the primary dysfunction is in the blood vessels of the lung. As those vessels become stiffer and more rigid, they cause a back fill of pressure and volume into the right heart. And the right heart is a muscle, although it's much more complex than the left heart. Because it has a U-shape to its inflow-outflow tract, which changes its contractility right off the bat [from the beginning of heart muscle contraction]. It's also a much lower pressure and lower resistance-high compliant system that when that compliance starts to go down and resistance goes up, the muscle is at a disadvantage. So it starts to dilate, it starts to fibrose and become less effective as far as contraction. And the way the right heart contracts, it's much more of a peristaltic contraction and down stream and kind of following this U-shape. So it's at a disadvantage structurally relative to the left heart. Patients who have right ventricular dysfunction and ultimately heart failure will develop shortness of breath and then will start to accumulate fluid. So they may get lower extremity edema first, or they may collect fluid in their abdomen, even have frank ascites. And as time goes on it just gets worse and worse. - You do echocardiography and additional, perhaps invasive testing in right heart failure? And then more specific treatment is available for right heart failure... - Yes, we do cardiac imaging. Echocardiography is certainly an easy way to look at the heart. Although it's not necessarily the best way to look at the right heart, because you just can't see all of it. Cardiac MRI is becoming very important in how we assess right ventricular structure and function. We do right heart catheterization to get pressure assessments and even some cardiac CT is sometimes helpful. But mostly cardiac MRI. There is no specific treatment for right heart failure. We target the pulmonary vascular bed, we do use some of the inotropes that we use for left heart failure. But they're probably much less effective for pure right heart failure than they are for the left heart. And I think that's one of the real challenges right now - is finding targeted therapy for the right heart failure.
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Shortness of breath? Learn more and get a better lung disease treatment plan with top experts. Visit our Online Expert Centers at https://diagnosticdetectives.com/expert-centers/ Exclusive interview / Dr. Anton Titov MD and Professor Dr. Aaron Waxman MD, leading pulmonary arterial hypertension, right heart failure and lung disease expert. Find out exact cause if you have shortness of breath - get a precise diagnosis and best treatment for shortness of breath root cause. - Your research focuses on how blood vessels and lungs change in disease. You show that inflammation in lungs leads to change in vascular architecture, the lung undergoes, the blood vessels undergo remodeling process. You also have a mouse model that mimics closely the pulmonary arterial hypertension. So how does your research help people with lung disease? What are the current directions of your research in pulmonary arterial hypertension and other lung vascular diseases? I think the things that we've learned from some of the work we've done here, is really the role of inflammation in driving vascular remodeling. We've looked at several aspects of inflammation and we've used a number of models. You mentioned the mouse model that was an IL-6 over-producer that remodeled their lung blood vessels much like human disease. Although it's still not a clean model of human disease. Also in collaboration with Dr. Jane Leopold in cardiology, we've developed a large animal model using a pig model, where we can tie off the inferior pulmonary vein and that drives a timed remodeling of the pulmonary vascular bed and the right heart. So we've been able to use that as a model of progressive pulmonary vascular remodeling and kind of an accurate timing of right heart dysfunction and eventually right heart failure. And we've been able to look at different things like administering stem cells using an intracoronary approach and showing viability of those stem cells. That model may also allow us to ask the question about devices. And could we put in a ventricular assist device in the setting of right heart failure that might actually help remodel the vascular bed and obviously support the right ventricle? But questions about pulsatile blood flow versus non-pulsatile flow... There may be benefit to non-pulsatile blood flow in the pulmonary vascular bed. But I think getting back to your question about how it is affected how we treat patients, we right now start to do clinical trials in anti-inflammatory treatments, including anti IL-6 or medicines that affect targets to the IL-6 receptors and downstream effectors of those receptors as well as stem-cell approaches, and even device approaches. - It's certainly very interesting because it has direct clinical implications and can help understand the pathophysiology of the lung disease better for patients with lung diseases.
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Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. As I said earlier, the problem with the diagnosis of amyloidosis is that the manifestations are so varied and they mimic many other conditions. So if you don't think of amyloidosis, and don't do the right test, and the right test is either to do a biopsy and look at it under the microscope or to refer the patient to us where we can do our imaging procedures, then it's very difficult to make the diagnosis. So the main issue is to think of the right thing. In the case of the individual whom you mentioned, multiple myeloma might not have been very far from the correct diagnosis. Because multiple myeloma is part of a group of conditions called monoclonal gammopathy, and multiple myeloma is a malignant cancerous condition, but the same cells that are cancerous in myeloma can also cause amyloidosis. Multiple myeloma itself can cause amyloidosis, but similar cells or the same sort of cells can cause amyloidosis. In fact, the commonest type of systemic amyloidosis is caused by these cells, where the cells themselves are not cancerous, they don't replicate out of control, they don't invade anywhere else, they don't damage the local organs where they are. They just produce an abnormal protein and that forms the amyloid deposits. So the key thing that's happening in amyloidosis and the formation of amyloid, is that you have normally soluble proteins like, for example, egg white, which is clear and translucent when the protein is soluble, but if you fry your egg or a boil it, it becomes insoluble, hard and white, and opaque - so proteins can be in different physical states. Normally soluble proteins in the body about 30 different proteins that are known so far, they can misfold and become abnormal, and deposit as amyloid fibrils, which are aggregates, clumps of these proteins that have undergone a change in their physical form, and they become insoluble, and they lay themselves down in the tissues of the body. And the mystery is not why this happens, because now we understand that in recent years rather well, we understand the physical and biophysical processes of amyloid fibril formation. The big mystery is why doesn't the body get rid of them? Normally the body is extremely efficient at getting rid of abnormal debris. If you break your leg, falling off your bicycle, and you have a pint or two of blood in your leg and broken bones etc, as long as you don't get infected, the body heals it all up very well. Everything gets remodeled and returned to its normal anatomy. Clots get removed, the bruising, if you have a bruise, it goes away, nothing terrible happens, it all clinically silently fades away, because there are cells in the body, which are called macrophages, which are very competent at recognizing abnormal debris, and clearing it away. The mystery is why do they not clear away amyloid deposits, which are just made of the body's own proteins, they are not made of anything abnormal from the outside. It's just the normal stuff in an abnormal form. That's a big mystery, which nobody has solved, but that's been my key interest in treating this disease now for many many years, trying to understand why that failure of clearance exists and to try and remedy it with therapeutic interventions. And we're now reasonably well on the way to doing that successfully.
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Shortness of breath? Learn more and get a better lung disease treatment plan with top experts. Visit our Online Expert Centers at https://diagnosticdetectives.com/expert-centers/ Exclusive interview / Dr. Anton Titov MD and Professor Dr. Aaron Waxman MD, leading pulmonary arterial hypertension, right heart failure and lung disease expert. Find out exact cause if you have shortness of breath - get a precise diagnosis and best treatment for shortness of breath root cause. - What is new in treatment of pulmonary arterial hypertension? - So the treatment of pulmonary arterial hypertension has come a long way since I got involved. When I first got involved, there was only one drug, well, two drugs - there were calcium channel blockers, which are pretty ineffective for the vast majority of patients with pulmonary arterial hypertension, and epoprostenol, which was called Flolan at the time, which is an intravenous therapy. Prostacyclin was the other drug. And it really had a big impact on patients, but it was a very complicated therapy that involved intravenous continuous infusion, external pumps, and Hickman catheters. Over the course of the past 20 years the focus in pulmonary arterial hypertension has been on three main pathways: endothelin pathway, nitric oxide pathway, and prostacyclin pathway. So there been a number of drugs developed - both intravenous and oral, and even inhaled, but none of them are home runs. They're all effective in pulmonary arterial hypertension to a certain extent. They've had a tremendous impact on survival and functional status, quality of life. But there's still tremendous room for much more development [of pulmonary arterial hypertension therapy]. More and more the focus is now on metabolic modulators, things that change mitochondrial function, things that are antiproliferative, even some chemotherapeutic [medications] repurposing going on, and also anti-inflammatory targets, in a complicated way. So I think we're moving much more into the realm where we are starting to treat pulmonary arterial hypertension like a metabolic neoplastic disease more than a vasoconstrictor disease, which is what most of the focus has been on. So for somebody who has been diagnosed with pulmonary arterial hypertension and the diagnosis has been established, are there stages of therapy or lines of therapy, similar to the neoplastic disease treatment? What is a typical progression of treatment for a pulmonary arterial hypertension patient? - So we grade patient severity of disease much like we do in heart failure. And we use the WHO functional class approach. And really over the past two to three years what's become the standard of care for pulmonary arterial hypertension is using combination therapy, just like we would for most any other complicated disease. These drugs for pulmonary arterial hypertension tend to be quite expensive, so there's been a reluctance over the past years purely because of expense. Now we have clinical trial data that show clear benefit in pulmonary arterial hypertension of using a combination therapy. So, depending on how sick a patient might be - and by how sick I mean how short of breath, how limited are they? Are they having issues with heart failure at the time? We might start out with just oral therapy and using a combination of two drugs. Usually it's going to be a phosphodiesterase 5 inhibitor in combination with an endothelin antagonist. As patients with pulmonary arterial hypertension progress, then we start to think more and more about prostacyclins. But the truth is that prostacyclins still are our best therapies and probably if we use them earlier in disease, we'd get even better results. So it's a moving target how we treat patients. But what's good is that it's becoming a more complex targeting of disease or at least a therapeutic approach to pulmonary arterial hypertension, which I think is having better outcomes.
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Dr. Carl Bell, renowned psychiatrist, public health expert, and author. Professor of Psychiatry, University of Illinois, Chicago. Bio: https://en.wikipedia.org/wiki/Carl_Bell_(physician) Hello. Today we're discussing very important topics on suicide prevention. We are with Dr. Carl Bell who is Professor of Psychiatry and Public Health at the University of Illinois in Chicago. Dr. Bell is an international researcher at the National Institute of Mental Health. He is also an author of more than 575 books, chapters and articles addressing various issues of psychiatry, especially focusing on suicide prevention and general violence prevention and on misdiagnosis on various psychiatric illnesses, including manic depressive disorders. Dr. Bell has been honored by multiple awards. He is a member of the National Medical Association, former Chairman and the Section of Psychiatry. He's a member of Black Psychiatrists of America and a fellow of American College of Psychiatrists. He's a founding member and past Board Chairman of the National Commission of corrections. He is also a member and former director of the American Association of Community Psychiatrists. Dr. Bell, thank you very much for talking to us today about this important issue of suicide prevention. Welcome! Thank you. Thank you. So it has been recently a couple of very high profile suicides, obviously, of Kate Spade, and Anthony Bourdain. So that brought this very important topic of mental illness and suicide again at the forefront of the discussion. But the question that you researched very extensively is that it's possible to prevent the mental illness. Is it possible to do so? And if so, how to prevent mental illness? Well, in 2009, we there was a community of the Institute of Medicine and we wrote a rather large book on prevention of mental health and mental illness. In that book, what became very clear was that - let me let me back up for a second - the first conventional report was by Institute of Medicine in 1994. But back then the science was not as robust as it is now. However, fortunately, that report spurred a lot more research so that by 2009, there was a lot more research that was done on the prevention of schizophrenia, prevention of suicide, prevention of violence. There's just a lot of conventional science that has occurred in the 15 years since the first report. And it became very clear that part of the problem was that there was all the science saying mental illness and suicide could be prevented, but it wasn't really implemented. And that became really the problem. At that time I was actually on the Advisory council of the National Institute of Mental health, and when we went through the portfolio of NIMH, what you found was that there were, in fact, all these prevention projects, but they have not been implemented. We were somewhat critical of NIMH because of their lack of implementation. And at the time, it turned out that I mentioned it, 4 strategic goals. The fourth one was implementation. So when Dr. David Satcher, the Surgeon General told us that there was psychosocial prevention and biochemical prevention. Biochemical prevention is the easiest to implement. So for example, putting iodine in table salt prevents cretinism (congenital hypothyroidism), forcing people to wear seatbelts laws, prevents motor vehicle deaths, then the psychosocial prevention strategies, for example, I had a grant from the NIH to prevent HIV infections in Durban, South Africa. And essentially what you do in the psychosocial intervention is you teach people how to live safely. Those are hard to do, because it takes a lot of work.
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Shortness of breath? Learn more and get a better lung disease treatment plan with top experts. Visit our Online Expert Centers at https://diagnosticdetectives.com/expert-centers/ Exclusive interview / Dr. Anton Titov MD and Professor Dr. Aaron Waxman MD, leading pulmonary arterial hypertension, right heart failure and lung disease expert. Find out exact cause if you have shortness of breath - get a precise diagnosis and best treatment for shortness of breath root cause. - What is heart failure with preserved ejection fraction? Why it's important to find the diagnosis of heart failure? And what treatment options are available for patients with heart failure with the preserved ejection fraction? Heart failure with preserved ejection fraction, or diastolic dysfunction, or HFpEF ["Hef-Pef"], as people call it quickly. It is probably one of the most difficult aspects of treating heart failure right now. It's more prevalent than heart failure with reduced ejection fraction, which is what we think about with systolic heart failure and congestive heart failure. What happens is people get older, or have HFpEF probably often as a complication of the metabolic syndrome, diabetes, cholesterol hyperlipidemia, and obesity especially. The heart starts to become stiffer, and as that stiffness goes on, it starts to fail at relaxation. So the relaxation phase of the contractility becomes compromised. The response to that is to build up fluid in the system. So the kidneys start to retain fluid, volume goes up. With volume we get increased pressure, and over time you start to see a rise in pressure in the left side of the heart at the end of the filling phase. So we see an increased left atrial pressure and an increased left ventricular end diastolic pressure. That in itself creates an inefficient system, so that patients have exertional intolerance or shortness of breath with exertion because of that. And then over time there can be an increase in that pressure back-fill into the lungs, and if not treated aggressively, the vessels in the lungs start to become stiffer and thicker, much in the same way as any other form of pulmonary hypertension. And you start to impact right ventricular function. One of the difficult things is, other than diuretics and treating metabolic syndrome, we don't have any clear targeted therapy for heart failure with preserved ejection fraction. There are some data that suggests phosphodiesterase 5 inhibitors are helpful in those patients who already have had a change in their pulmonary vascular resistance But otherwise, if there's no PVR problem, we don't have a clear treatment at this time. - Is there anything for HFpEF therapy from a medical devices standpoint? Because medical devices in heart failure and even surgical approaches are developing quite rapidly. - There is right now not so much for heart failure with preserved ejection fraction. Obviously, for reduced ejection fraction there are lots of device options and growing device options as far as ventricular assist devices and and other forms of augmented flow. But for HFpEF itself - unless... You can look at it from a physiologic standpoint: Patients who have hypertrophic cardiomyopathy often have similar physiology, although it is extreme compared to heart failure with preserved ejection fraction. In those patients it's a different disease, and they're candidates for transplant, whereas for HFpEF itself generally that's not a disease state that we think about [heart] transplant...
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Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. The basis of all our treatment of systemic amyloidosis is to try and get rid of the protein that is forming the amyloid fibrils. If you can get rid of the abnormal protein, or sometimes it's a normal protein but you've got too much of it, whatever it is. If you can get rid of the precursor protein that makes the amyloid deposits, that is the way to stop the disease progressing and to make people better. And so all current treatment consists of keeping the patient alive long enough to get rid of this precursor protein. So we go to extreme lengths to do that, so kidney dialysis, kidney transplantation, liver transplantation, heart transplantation - every possible measure to keep the patients alive long enough to get rid of the protein that's causing the damage. Unfortunately, you can't always do that. The patients, as we said before, have a delayed diagnosis, they are so far advanced you can't do these heroic measures and so you can't save them. Also another problem is, you can't always get rid of the abnormal protein. So we have very good treatment now for monoclonal gammopathy, which is the main cause of the commonest type of systemic amyloidosis, and sometimes those new treatments work, sometimes they do not work, and then of course we have a group of conditions, which are hereditary, where there's a gene mutation that encodes an abnormal protein, and that makes amyloid, and in such cases we don't have any intervention, which can get rid of that. And so these are very challenging cases to manage. We hope that the new treatment which would get rid of existing amyloid deposits will have a big impact and enable people to stay alive long enough to benefit from interventions, which could work and the people with genetic disease, they would need to have obviously repeat dosing of our treatment to keep getting rid of the amyloid, which will otherwise recur. Our proposed treatment is not a miraculous cure in its own right, it requires the other interventions, you always have to be doing the other things. So it's important to understand that. The other thing that's very important to understand is the very very tenuous nature of drug development. Most drug development fails, very very few drugs which start off with an invention in the laboratory and screening of compounds, and the animal pharmacology and toxicology, eventually get into patients - most of them don't go all the way. They fail for a wide variety of reasons, not the subject of this interview, but this is a well-recognized phenomenon. So until the drug is actually licensed by the regulatory authorities we can't really say "it's a drug" or "a medicine" - it is not. - It's a "candidate"... It's something that we're trying to develop, and it's exactly the same with this treatment. So whilst we are optimistic about it and hopeful and the results so far are unprecedentedly encouraging. We've actually shown for the first time there's an intervention that can make amyloid go away in a short space of time, safely, and furthermore, it shows that it benefits the patients. People are still arguing how does exactly amyloid cause disease, and my belief has always been, and I think the evidence is in favor of it, that the major problem caused by amyloid deposits is the disruption of the structure and function of the tissues. Well, we've got a treatment that makes amyloid disappear. What happens? Organ function gets better in the liver, in which it is easy to measure organ function - that's what we've done so far. If we can do the same thing in the heart, it will be wonderful. We haven't got there yet, but at the moment this is a candidate treatment, it's not a medicine yet, we need to be straight about that. Dr. Anton Titov MD How might your drug work for the Alzheimer's disease treatment?
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Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. - Is there anything people can do to decrease the risk of getting Alzheimer's disease? Maybe to prevent it, maybe it's different for a certain subset of people. What can be done to prevent Alzheimer's disease, from your large experience? Well, I'm not a dementia specialist, so I'm not necessarily the right person to answer that, but I obviously know about this field somewhat, and the fact is that we should probably in this context talk about dementia rather than Alzheimer's. Alzheimer's disease is a particular form of dementia, it's a specific disease, you know, diagnostic criteria, so on and so forth. Dementia is a broader problem, and a very important cause of dementia is vascular, it's related to atherosclerosis, vascular disease - the same thing that gives you heart attacks, strokes, and so on. And there are many other causes of dementia too, bangs on the head, for example. What can you do to mitigate that? All the obvious advice around reducing risks of vascular disease, cardiovascular disease, are critically important. And all old people who are diagnosed with Alzheimer's disease have inevitably got some atherosclerosis, which probably makes a more or less significant contribution to their dementia. So anything to mitigate that is obviously important: so - not smoking, not being diabetic, not being overweight, taking exercise, eating a balanced diet and so on. All those things are healthy and sensible, and by mitigating cardiovascular risk, and mitigating vascular disease, atherosclerosis in the brain arteries as you get older, will definitely make a significant contribution. Those are the things to do. Other than that, there's a lot of interest in why do some people become more demented than others, and there's a lot of interest in the fact that if you keep your brain active, maybe that protects you. My personal view about that is, if you start off with a higher intelligence and you lose a proportion of it, you've still got a higher cognitive function than if you started at a lower intelligence level and lower educational level, and then you lose 25% of it, then you may be severely compromised. So I'm not aware that there is compelling evidence that you can do brain exercise and keep your brain active, better than if you are not doing it [brain exercises]. On the other hand, clearly, the more interested you are, the more alert, the more perceptive - clearly, that is better and one can train one's brain to be better. One learns things all the time, you keep learning things - they are all sorts of tricks to keep one's cognition better. But I'm just not convinced that there's going to be a route to protecting cognitive function by doing brain exercises. A large proportion of that evidence, which is observational, that smarter more educated people and so on, don't get so much dementia is because they started at a higher level. If you don't smoke and you don't have type 2 diabetes, and you control blood pressure, I wanted to mention that before, it's very very important - all these things contribute very substantially to vascular disease. And we know for a fact, irrevocably, that if we control control those things, and controlling levels of cholesterol - statins are very very important, I know that's an extremely controversial area, but I am a very powerful believer in the amazingly strong scientific evidence from placebo-controlled double-blind epidemiological studies that statins are good for you. Тhey have side effects in a tiny minority of people, but they are amazingly good drugs to prevent vascular disease, so that's a crucial thing. So all of those things that are protective against vascular disease, atherosclerosis are definitely good for preserving cognition as well. As for Alzheimer's disease, we need to understand it itself. We have to understand more about what it is. There's now a flurry of interest in - Dr. Anton Titov MD
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Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Dr. Anton Titov MD Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. That's the good news. The bad news is because it's so easy to do, people have done it in all sorts of other investigations and produced wildly misleading results. You mentioned "It's a risk marker" It is indeed a very modestly significant risk marker for cardiovascular disease. But that story was greatly overhyped and people started talking about CRP as a "risk factor". A "risk factor" is something which actually contributes to the disease. Cholesterol is a risk factor, we know that cholesterol causes atherosclerosis. You've got too much - you get atherosclerosis. You lower it - you protect against atherosclerosis. - [AT] Again, playing loose with the the words! - [MP] It's not only playing with the words, it's also a serious scientific error, the conflation of association with causality. So people did epidemiological studies that seem to be large, because there were thousands of people involved, but the number of events, number of heart attacks in them, for example, was very small. Now, it doesn't matter if you've got 10,000 people in a study if you've only got a hundred heart attacks - and then if you divide them into quintiles of what their CRP was a year before or 10 years before, you can get all sorts of funny results, so the original epidemiological results suggested a fantastically, incredibly literally, unbelievably high association between having a raised baseline CRP and whether you have a risk of having a heart attack later on. But when the epidemiology went up to proper epidemiological scale and hundreds of thousands of people were tested, either in meta-analyses or in very big studies - it turned out that the association was much much weaker and it's still there, but it's pretty modest and all it really means, and you find the same association with many other inflammatory markers, it's nothing specific to CRP, you find it with low albumin, when the CRP goes up, albumin goes down, sedimentation rate [ESR], or the cytokines, all sorts of things like that, so this was a complete conflation, wrong conflation of association and causality, and it got exacerbated because people did experiments in vitro with commercial sourced CRP, which was impure, contaminated with bacterial lipopolysaccharide, which is very pro-inflammatory, and they put that onto cells and the cells went "whoa!" And they said "this is the CRP causes atherosclerosis!" - they even did in vivo experiments, where they infused this dirty stuff into people and they got lots of inflammation going on - [AT] the body has strong response to bacterial polysaccharides... - [MP] Yes... So CRP was claimed to be pro-inflammatory, and it turned out that it isn't. Eventually we were so concerned by these reports and not being able to reproduce them in vitro, or in an animal models and so on, we made pharmaceutical-grade human CRP from human donor blood, very laborious, very expensive, and we infused it into volunteers, healthy volunteers and guess what happened to them? Absolutely nothing! So we showed that CRP is not pro-inflammatory if you're healthy, so the whole story of CRP as a risk marker for atherosclerosis, and for cardiovascular risk - that has evaporated, and the final nail in the coffin was what's called "genetic epidemiology", Mendelian randomization. If you find the genes which encode different levels of C-reactive protein [CRP] at baseline, at different acute-phase responses, and there are such genes, there are various polymorphisms in the human population. Some people have genes which give them a low baseline CRP, 0.1 mg per liter, and other people go around with a CRP baseline 5 mg per liter. When they have an acute phase response, correspondingly the one goes up more than the other.
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Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. - Hello from London! We are with Professor Sir Mark Pepys, who is the Director, Wolfson Drug Discovery Unit, Centre for Amyloidosis at the University College London Professor Pepys is a global expert in amyloidosis, a fatal condition resulting from amyloid deposits in many organs and tissues. Amyloid is also a key factor in Alzheimer's disease. Professor Pepys was educated at Trinity College Cambridge and University College Hospital Medical School, London and then he returned to Cambridge as a research scholar for his PhD in immunology After 22 years as Head of the Immunological Medicine Unit at the Royal Postgraduate Medical School he became Professor and Head of the Department of Medicine at the Royal Free Campus of University College London. Professor Pepys's groundbreaking work on amyloidosis treatment and his current work to extend his therapy to the treatment of Alzheimer's disease has been recognized by numerous awards and memberships. He is a Fellow of the Royal Society, a Founder Fellow of the Academy of Medical Sciences, and in 2012 he was created Knight Bachelor ["Sir"] for his services to biomedicine. Professor Pepys, hello and welcome! - Thank you! Dr. Anton Titov MD
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Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. Professor Pepys, from the enormous experience that you have, your research and clinical work, what do you think is the future in Alzheimer's disease treatment? What are the trends in Alzheimer's from your perspective? Where the hope in treatment might come from? So many clinical trials have been unsuccessful, $ billions have been spent. What the future might hold? [for Alzheimer's disease treatment] Well, I think it's very encouraging that there is much more focus and attention on this important field than there had been in the past. Compared to the cost to society of Alzheimer's disease, there had been significantly less money invested in studying it, and clinically, trying to investigate Alzheimer's disease, than in some other areas... So I think that there is a great focus on it, people have prioritized it very highly. That can only be good. As to where the advances are going to come from - my guess is not any better than anybody else's, I am afraid. There are a lot of very intelligent and industrious people, companies, organizations working on these very challenging problems. And I'm not sure that any of us can predict where any breakthrough is going to come. I think what's important is to have an open mind, not only to focus on one particular target, but to focus on many targets and to have an open mind about mechanisms of pathogenesis. We have to keep on working on what actually causes the disease, what actually kills the cerebral cells. I mean there are many many different avenues, and the only way to make progress, I believe, is to keep on with the earnest scientific inquiry to understand things better. Then once you understand things, you have an opportunity to challenge them, and to treat them. At the moment our understanding is incomplete, it doesn't enable us necessarily to do that in a rational way and unfortunately, the way society is organized, and the way drug development proceeds and so on - people tend to get in a track and then everybody does the same, more or less the same thing... - A herd mentality in science does exist! - It certainly does! Herd mentality in a way sort of devalues the quality of the decision-making. I think it's more than just that. But certainly the costs of drug development are so vast, that the companies have to be risk-averse, they can't take huge gambles with their shareholders resources and spend vast amounts of money on something, which is less validated or less popular, and so they do tend to go in similar directions. I think that's a very difficult thing to overcome, but now that governments are very focused on it and have made it - in the G8 - it's a big priority, and different national governments have made dementia a great priority - that can only be a good thing. I hope that it will lead somewhere. As to whether we'll get cures and so on, I think that's probably fanciful. Once the brain is badly damaged, its capacity to recover is probably limited. But who knows? We're seeing amazing things with stem cells and other areas, so maybe there are possibilities for improvement. But the most one could hope for, and I think it would be a huge advance, would be to arrest progression. If we could arrest the progression, when people have mild cognitive impairment or very early Alzheimer's, people will continue to function, then wouldn't need to be cared for so much, they would have quality of life. They're mostly old, they would succumb to other illnesses before they ended up with end-stage dementia. So I think that's what we have to hope for... Dr. Anton Titov MD
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Hoe kies je de perfecte medisch specialist om je probleem te bestuderen? Het is belangrijk om de beste specialist te selecteren, die de wereld te bieden heeft. Geen enkel ziekenhuis heeft voor alle aandoeningen de beste artsen in huis. Ons netwerk behoort niet tot een bepaald ziekenhuis, universiteit of land. Wij zijn derhalve vrij om de perfecte arts voor u uit te zoeken, onafhankelijk van affiliatie of lokatie. Deze perfecte specialist zal de beste zijn om uw probleem te beoordelen. De kennis en ervaring van de arts moeten perfect passen bij het probleem dat u heeft. Dit is ons enige criterium voor de selectie van een medisch specialist voor u. De arts kan in ieder ziekenhuis, universiteit of land werken. Wij vinden de perfecte specialist voor u op de volgende wijze. We beginnen met een gedetailleerde analyse van uw medische informatie en volgen dan drie stappen: Stap nummer 1: Wij bestuderen de internationale medische literatuur om de vijf beste specialisten ter wereld te vinden. Wij selecteren alleen artsen die uw specifieke probleem kennen van onderzoek en behandeling. Zij moeten ook aan de beste ziekenhuizen en universiteiten verbonden zijn. Stap nummer 2: Wij gebruiken aanbevelingen van ons internationaal netwerk van medisch specialisten en bestuderen ook informatie afkomstig van internationale congressen. Stap nummer 3. We sturen een korte beschrijving van uw probleem naar medisch specialisten die u mogelijk zouden kunnen helpen. Deze artsen laten ons dan weten of hun expertise bij uw probleem past. Zodra wij advies hebben gekrijgen van de medisch specialist van onze keuze, bestuderen wij zijn aanbevelingen zorgvuldig. Wij vragen de specialist om ons de diagnose en behandeling uit te leggen. Wij vatten dan zijn aanbevelingen samen in een gedetailleerd, schriftelijk verslag, dat meestal 10 tot 15 pagina’s lang is. Ons rapport zal bovendien achtergrondinformatie over uw probleem bevatten, alsook een samenvatting van alle aspecten ervan. Na bestudering van het verslag, neemt u telefonisch contact met ons op om alle vragen te beantwoorden. We kunnen ook met u communiceren via email of videoconferentie. Indien nodig, kan de medisch specialist aanvullende vragen worden gesteld. Selectie van de perfecte medisch specialist is de belangrijkste factor bij het oplossen van uw probleem.
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Shortness of breath? Learn more and get a better lung disease treatment plan with top experts. Visit our Online Expert Centers at https://diagnosticdetectives.com/expert-centers/ Exclusive interview / Dr. Anton Titov MD and Professor Dr. Aaron Waxman MD, leading pulmonary arterial hypertension, right heart failure and lung disease expert. Find out exact cause if you have shortness of breath - get a precise diagnosis and best treatment for shortness of breath root cause. - Becoming short of breath is a common symptom, and shortness of breath has many causes. One of those causes could be pulmonary arterial hypertension, a relatively rare situation, but nevertheless a very important disease. How to recognize causes of shortness of breath correctly? So I think that's an important fundamental question because so many people who do complain of shortness of breath are kind of given a diagnosis without a lot of evaluation. And because of that and also because we wanted to actually discover patients with pulmonary hypertension earlier in their disease, we about seven years ago now set up a Dyspnea Evaluation Program. And what we learned very quickly is, #1, that shortness of breath as a complaint is probably second only to pain when people go to their doctors. Whether they go to their primary care, whether they go to a cardiologist or a pulmonologist. And generally those are the three kind of doctors that people with shortness of breath go to. We then learned very quickly that if you're young - and by young I mean less than 55, you'll often be told "Oh, it's asthma". And without any evaluation you'll be given inhalers and sent on your way. If those inhalers don't work - you don't have asthma. But still people were treated [incorrectly, as if they had asthma] If you are older than 55, you were often told you either had COPD [Chronic Obstructive Pulmonary Disease] or probably heart failure. And if you think about it, all three of those diseases are actually very easy to diagnose and rule out, which many of these patients didn't have. So we actually found that when we talk about unexplained dyspnea [shortness of breath], or unexplained exertional intolerance, we only need three tests to put patients into that category. And if they've had pulmonary function testing that is either normal or doesn't explain their limitation, if they've had an echocardiogram that doesn't explain their limitation or is normal and some sort of chest imaging, which whether it's a chest radiograph or a CT scan. Most patients aren't symptomatic at rest. So to expect any of these tests to tell you why someone is short of breath when it's not an obvious problem is asking a lot of the tests. So we actually developed a program here based on invasive cardiopulmonary exercise testing, where we put in a right heart catheter and we specifically use a Paceport Swan-Ganz catheter, so that we can measure pressures out of the right atrium, right ventricle, and pulmonary artery, we wedge that catheter every minute during the test. And we can get a left atrial pressure. And then we also put in a radial artery catheter to measure pressure. And we can then sample blood from both of these catheters. And then we do a full cardiopulmonary exercise test. And it's an incremental load test, so we start out at rest and then we'll do about two minutes of unloaded cycling and then we'll do a ramp protocol depending on the patient's abilities to peak exercise. And then we'll also collect data on the recovery phase, and then usually one hour later we'll get one last set of blood samples. So every minute of this test we're capturing the waveforms off the catheters, we are sampling the catheters, we're measuring gas exchange continuously. So we truly have access to Fick principle physiology.
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How to treat leg or arm lymphedema after cancer surgery? Choosing the right method of lymphedema surgical treatment has many nuances: choice of method, choice of best surgeon, costs and logistics of treatment all factor into the patient's decision where to go for lymphedema treatment after successful cancer surgery. This is our client's story, and we are very close to the optimal solution!
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Shortness of breath? Learn more and get a better lung disease treatment plan with top experts. Visit our Online Expert Centers at https://diagnosticdetectives.com/expert-centers/ Exclusive interview / Dr. Anton Titov MD and Professor Dr. Aaron Waxman MD, leading pulmonary arterial hypertension, right heart failure and lung disease expert. Find out exact cause if you have shortness of breath - get a precise diagnosis and best treatment for shortness of breath root cause. - Anticoagulants are widely used in clinical practice in patients with pulmonary arterial hypertension. But blood thinners, as they are also known, have a lot of significant side effects. And the major side effect is the risk of bleeding, including intracranial bleeding, gastrointestinal bleeding. How to balance risks and benefits of anticoagulants when they are used for pulmonary arterial hypertension? So the whole role of anticoagulants in pulmonary arterial hypertension is now in question. Originally, anticoagulants were started because pathologically, when the disease was first described in the 1950s, there was recognition of what was probably in-situ thrombosis. As such, people start asking questions - if we have no other treatment options and we put patients on coumadin, will it have an impact on disease? There was a suggestion that had a small impact on survival in pulmonary arterial hypertension. Since that time and really over the past five years, based on studies that have been published out of the European registries, the US registries and even out of our own patient population here, we've recognized that probably there's not a lot of clinical benefit, and we're not convinced anymore that the risks of anticoagulation, especially lifelong anticoagulation, outweigh the benefit. So for many of us, we've actually stopped using routine anticoagulation. For those patients with pulmonary arterial hypertension who might have chronic thromboembolic disease, or who have had known blood clots, obviously they will be anticoagulated. But now less and less we anti-coagulate patients with pulmonary arterial hypertension, we have no indication that there's a lot of benefit from it. - So it also speaks that there's a lot of research going on in the vascular lung diseases, and the new medications are becoming available, and the older ones that were empirically used - they're being phased out, in a sense. - In many ways, yes...
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Top doctors share knowledge and experience on prevention and treatment of medical problems. Discover better diagnosis, treatment and prevention of cancer, heart disease, autoimmune disease, mental health and brain problems - from world's best medical experts. Talk to us! Visit us at diagnosticdetectives.com
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Brain tumor treatment requires nuanced decisions by patient and family. Choice of surgeon is not always obvious - but consequences of being treated by surgeons who do not fit the case perfectly can be devastating. This is an instructive and dramatic story of a young patient who was diagnosed with a brain tumor in London and had to have three brain tumor surgical operations in a row...
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Professor Sir Dr. Mark Pepys explains links between Amyloidosis, Alzheimer's disease, inflammation and C-reactive Protein. Exclusive interview. See more at Online Expert Centers at https://DiagnosticDetectives.Com/expert-centers Get precise diagnosis and best treatment plan from world's top medical specialists selected to fit your medical problem precisely and perfectly. Professor Pepys, is there anything else you'd like to discuss regarding your work, research, sharing your wisdom? Well, there are two things which I'm very passionate about: one is, people need to understand what science is and how it's conducted. And I think that that is not well taught, people do not have adequate scientific education in most, probably in all, the developed countries, which I think, to some extent, is unbelievable! The world is such a scientific place, we all go around with these devices in our hands, which are full of high-tech, we travel in a very high-tech way, we communicate in these extremely high-tech ways, and yet people are not adequately taught about science, the nature of science, what it involves, the reproducibility of it, the necessity for transparency and honesty. Richard Feynman, the great Nobel Laureate, an American physicist, he famously said "You have a duty as a scientist, when you present your hypothesis, to show all the evidence which is against your hypothesis just as much as you show the evidence in favor of it. So that people can make up their mind, do they believe your hypothesis or not?" He said "the best way I can explain this is to contrast it with advertising", OK? Advertising is the complete opposite: you say "my product is the best", you don't say "Somebody else has got something which is almost as good, or might be cheaper..." You say "no, buy my product because it's the best". That's all you ever say in advertising. Science has to be the complete opposite, and even the scientists don't always get that. And the scientists don't understand, some of them, what science is about! As in the example of association and causality. So in the midst of that disagreement about the role of CRP, a very famous American cardiologist, who fancies himself as an epidemiologist, actually wrote in some comment on the web or somewhere, that my failure to recognize that CRP was causative in myocardial infarction, was complete ignorance and stupidity - how could anybody ignore the compelling body of evidence that proved that CRP causes heart attacks. And we see where that went (CRP "causing" heart attacks) We completely disproved it eventually with genetic epidemiology as well as by all the in vivo and in vitro experiments. So you know you have to understand what science is about. People need to be taught more about it. Because if they are not taught, the population becomes tone-deaf to science as I say. If you are tone-deaf, you can't appreciate music, if you are tone-deaf to science because you haven't been educated about it and don't know what it's about, you can't understand anything about the modern world. Homeopathy is a classical example. Homeopathic medicines are nothing! They are zero. You've got a number of molecules you can't count in your "medicine", because they've been diluted deliberately so far that they're not there! So how can that make you better? If you've got a little pain in your big toe, it probably doesn't matter. But if you've got asthma or cancer or a bacterial infection and you rely on homeopathic "medicines", you are going to die! This is a disaster! - AT: And it delays time to the correct diagnosis and correct treatment! The other thing which I'm very keen on is patient awareness, and making patients understand what their disease is. It's particularly acute in amyloidosis, which are the patients that I mostly deal with. It's a rare disease, it's incredibly complicated, and if you go on the web about it, you can find all sorts of really scary stuff, Well, it is a scary disease, it's a bad disease to have, but you need to have proper information. So I have been very active in the last few years to develop patient awareness for our patients, and indeed for patients with this disease all around the world. We created a fully interactive website for the patients, there's a forum where they can write in and have with moderated replies and so on. The patients find this extremely helpful. So they can look up on this website anything about any type of amyloidosis, the treatments, the complications of the treatments, what to do when, if, some things happen, and people in general find that extremely helpful. I think that is very important and being able to communicate is very important. So I know there's a lot of patient awareness going on and it's a necessary requirement in most health services that the clinicians and centers provide this, and we've been very active in promoting it in our field. That, I think, is an important thing to do if one can... Dr. Anton Titov MD
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Shortness of breath? Learn more and get a better lung disease treatment plan with top experts. Visit our Online Expert Centers at https://diagnosticdetectives.com/expert-centers/ Exclusive interview / Dr. Anton Titov MD and Professor Dr. Aaron Waxman MD, leading pulmonary arterial hypertension, right heart failure and lung disease expert. Find out exact cause if you have shortness of breath - get a precise diagnosis and best treatment for shortness of breath root cause. - So this is the theme that I clearly hear: multidisciplinary approach to diagnosis in finding the best treatment for any kind of condition. - Yeah, I think it's really the only way forward in medicine - We went back and looked at our patient population and we probably see on the order of two or three hundred new patients every year with unexplained shortness of breath. And we're following well over a thousand patients at this point. And what we learned was that the average time to diagnosis for the patients we've seen - and really it means to the time to where they were referred to our center is about two years. So these patients have been complaining of shortness of breath for at least two years, and over that two years many times people have spent upwards of a 100,000 to 150,000 dollars on diagnostic testing, repeating tests over and over again, because, I mean, physicians want to do something, and if they can't treat something, they're often going to order a diagnostic test. And even though that test has been done [before], it hasn't shown an answer, it's what the physicians are comfortable with, and so a lot of money is spent a lot of time is wasted in getting these patients a diagnosis... - It pays to get to the right experts!
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