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References J Zhejiang Univ Sci B. 2022 Jul 15; 23(7): 607–612 Biomaterials. 2020 Apr; 238: 119836. Int J Nanomedicine. 2023;18:5265-5287 Child Ballad 100. 1775. Pentangle. 1972.Willie O' Winsbury https://youtu.be/nwqP_yoszCE?si=C0NH51euOOTlPYn9 --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support
Wondering why your hormones are all out of whack? Ever feel like you're maintaining a delicate balancing act, but the scales just can't stay in place? Well, if that sounds like you, then it's time to join us as we dive into Dr. Norm Robillard's fascinating insights—on how an unhealthy gut might be disrupting your hormones. With decades of experience under his belt and countless research studies to back him up, this is one episode on midlife hormone balance that no woman should miss! Norm Robillard, Ph.D., is the founder of Digestive Health Institute and creator of the Fast Tract Diet. He is a strong advocate of natural and integrative solutions for functional gastrointestinal disorders, various forms of gut dysbiosis and related health issues, helping people globally through his consultation practice. The Fast Tract Diet was presented at Digestive Disease Week to give gastroenterologists a science-based treatment option for functional GI disorders and dybioses based on Dr. Norms 3 pillar approach. His award-winning Fast Tract Diet mobile app and Fast Tract Digestion book series make it easy to implement the Fast Tract Diet. In this episode, you'll learn: • How an unhealthy gut may affect your hormones. • What Dr. Norm's 3-pillar approach is and how it could help rebalance hormones. • The importance of probiotics in maintaining healthy gut flora. • Why food sensitivities can play a role in hormone health. • Plus, Dr. Norm shares his top tips for keeping your digestive system functioning optimally! So don't miss out – join us as we explore why your dysfunctional gut might be wrecking your hormones and what to do about it with our incredible guest, Dr. Norm Robillard! Tune in now—you won't regret it! Midlife women - let's take back our health and nurture our bodies, together! Join us for this eye-opening episode on why your dysfunctional gut is wrecking your hormones and what you can do about it with Dr. Norm Robillard! Tune in now to learn the secrets of a healthy digestive system and balanced hormones. It's time to start feeling like yourself again! (00:00): “The best doctor gives the least amount of medicine.” - Benjamin Franklin. If your gut is dysfunctional and running you crazy and you think you've got hormone problems, this episode is for you. (00:13): So the big question is, how do women over 40 like us keep weight off, have great energy, balance our hormones and our moods, feel sexy and confident, and master midlife? If you're like most of us, you are not getting the answers you need and remain confused and pretty hopeless to ever feel like yourself Again. As an ob-gyn, I had to discover for myself the truth about what creates a rock solid metabolism, lasting weight loss, and supercharged energy after 40, in order to lose a hundred pounds and fix my fatigue, now I'm on a mission. This podcast is designed to share the natural tools you need for impactful results and to give you clarity on the answers to your midlife metabolism challenges. Join me for tangible, natural strategies to crush the hormone imbalances you are facing and help you get unstuck from the sidelines of life. My name is Dr. Kyrin Dunston. Welcome to the Hormone Prescription Podcast. (01:06): Hi everybody. Welcome back to another episode of the Hormone Prescription with Dr. Kyrin. Thank you so much for joining me today for this discussion on dysfunctional gut issues. What's a dysfunctional gut? Well, think about your dysfunctional family. You know what I'm talking about, right? Holidays where people get drunk and fight start, or people are disconnected, all the dysfunctions that plague modern families. Well, your gut can be dysfunctional too, and maybe it's not something that you're aware of. What does that mean? How you evaluate it? My guest today is an expert in this and he is going to help you understand clearly how do I know if this is me, how do I get tested, what do I do about it? And really get the big picture and detailed picture on what's important. And we're gonna talk about Benjamin Franklin's quote, the best doctor gives the least medicines, not the most. (01:57): I know some people who go to the doctor and actually get angry when they don't leave with a prescription. Is that you? I really hope not, but it's very true. A lot of people get angry when they don't get medicines, but you'll be healthier overall when you take fewer or no medicines. They don't really fix the problem, they just mask them. Your gut health and microbiome are essential for your hormonal health. I will tell you why in this episode. So you wanna stay tuned for that. We talk about assessing low stomach acid at the Heidelberg Test. If you're not aware of that, we dive into that and much more. So I'll tell you a little bit about Norm and then we'll get started. Norm Robard is a PhD. He is the founder of Digestive Health Institute and creator of the Fast Track Diet is a strong advocate of natural and integrative solutions for functional gastrointestinal disorders, various forms of gut dysbiosis and related health issues, helping people globally through his consultation practice. The fast track diet was presented at Digestive Disease Week to give gastroenterologists a science-based treatment option for functional GI disorders and dysbiosis based on Dr. Norm's three pillar approach, his award-winning fast track diet, mobile app, and fast track digestion book series make it easy to implement the fast track diet. Welcome Norm Robillard to the (03:24): Show. Thank you Kyrin. Nice to be here. (03:26): All the way from Boston, Massachusetts with a distinctive accent. I did live there one summer when I worked at the Harvard School of Pub Public Health doing research and it's such a unique accent that I would pick out anywhere I went in the world. So thank you for representing the Northeast (03:45): , right? In fact, I've lived in California for 10 years and I came back and I still have the accent , (03:52): Right? So let's dive into this very important topic. We can't talk about digestive health enough when it comes to hormonal health. And if you're listening and you're still scratching your head going, Kyrin, I don't know why you talk about poop all the time. This is supposed to be about hormones, . You gotta get the memo that your poop is all about your hormones and your hormones are all about your poop. So there's this interconnection. So what really was your path to becoming so passionate about functional gut disorders? Well, let me back up. Let's start with what are functional gut disorders? I don't even think people are familiar with that term. (04:32): Yeah, well they should get rid of that term as quickly as possible. It's been around a long time and it doesn't have much meaning now because when that term came up, it was, they couldn't find anything organically wrong with you. But yet you had these i b s type symptoms, bloating, altered bowel habits, gas belching, and so they would think, okay, well everything's working, but you have these symptoms. So it's a functional disorder. But we now know that in many of these cases, really the planes hit the mountain. It's not functional and we know a lot more about what's going on. You know, with the more common use of breath testing. We know that there's often an overgrowth of bacteria in the small intestine and there should be very few microbes in the small intestine. That's where our own critical digestion takes place. So we now know there's overgrowths and there there's been some studies on which exactly which types of bacteria those are. (05:34): And basically it's our own microbes overgrowing in the small intestine. And newest studies are starting to focus on some of these what they call proteobacteria like e coli and Klebsiella species. But others have been identified as well, also with various functional, what they used to call functional GI issues. They now know that there's alterations in or intestinal bacteria as a whole. So we have these FILA of bacteria and other organisms such as BDIs firm, acutes, actinobacteria and so on. And we know that there's some significant imbalances there in in people that have these conditions. So in other words, we're find as we find out more about them, they're not functional, they're dysfunctional gut health issues. So it, you know, takes 10 years for things to catch up with what's actually happening in terms of nomenclature and the dogma and the literature. Right. (06:33): I agree. We should call it dysfunctional gut disorders, just like we have. Some of us have dysfunctional families, dysfunctional gut disorders. Exactly. So you mentioned symptoms of ibs. So how would someone self-identify? I could have a dis or now I'm saying I could have a dysfunctional gut disorder or I could have a functional gut disorder. How would they consider that that might be them? (06:56): Yeah, well I think that the symptoms of the, kind of the first sign, right? I mean we talked about gas and bloating. You might have a lot of belching or even flatulence, kind of some lower GI gas you might have cramping, reflux is one of those. In fact, acid reflux and I B s are very closely linked. Half the people with IBS have reflux symptoms and half the people with reflux have IBS symptoms. So there's a similar etiology there, but there's other ones, nausea, dehydration, fatigue. Some people don't gain weight or they lose weight. So there's a nutritional component there, which makes sense, right? If you have all of these microbes in your small intestine where, where your vili and the micro viop kind of the, the fibers on top of fiber fibers in all of the surface area in the small intestine, these vili are pretty kind of delicate. (07:51): And if you have a lot of bacteria in that area and bacteria produce toxins and protease enzymes that can damage the vili and the little enzymes, the brush border enzymes that that radiate out from these microvilli. And so if you don't have those, you won't break down disaccharides, you won't complete the final breakdown of starches. You may not digest and absorb fats well. So the SIBO can cause this mal-absorption that ends up overfeeding these microbes. And when you overfeed these microbes, many of them produce significant amounts of gases. Hydrogen methane, hydrogen sulfide. In fact there was one microbiology study done on these gut bacteria. And if they feed these bacteria essentially one ounce of carbohydrates, right? So some, many of the carbohydrates we absorb into our bloodstream, but many we don't. We take just 30 grams of unabsorbed carbohydrates feed them to, to microbes these gut bacteria. (08:56): They can produce 10 liters of hydrogen gas. So imagine, whoa, 10 liters of gas in your intestines from one ounce of of unabsorbed carbs. And of course there's a molecular food chain. Some microbes take the hydrogen that one type of bacteria produces and they turn it into methane. In the case of these akea organisms or sulfate reducing bacteria can take the hydrogen and turn it into hydrogen sulfide. So the bottom line is when you're not digesting and absorbing your food efficiently, you're overfeeding these microbes. They produce a lot of these gases and you can end up with a lot of these symptoms. So I think the symptoms to answer your question is the first sign that something's going on. And then you have to really begin to look deeper into what's happening. (09:43): Right? So just to recap, cuz that was very rich, what you just shared is if you're wondering could I have a functional gut disorder? Basically if you have any of the symptoms that Dr. Norm is talking about, right? The excess belching, indigestion, heartburn, reflux, gassy if you poop less than every time you eat, right? So if you have any degree of constipation, if you have loose stool, hard rabbit pellet stool, you know any symptoms associated with a gastrointestinal tract that wouldn't be diagnosed typically by your regular H M O doctor cuz they're looking for a structural problem or maybe they would diagnose you with reflux, but they're basically gonna give you a drug for it. Can you talk about the pitfalls? Because some people listening are gonna think, oh yeah, I've got reflux, it's no problem. My doctor gave me this proton pump inhibitor and so I'm fine now. I don't have a problem anymore. Dr. Norm. Yeah, what what do you say (10:45): To that? Yeah, my 18 years of consulting in this field as a consulting microbiologist, I really focus on holistic and dietary and behavioral solutions and perhaps some dietary supplements mostly aimed at improving digestion. Because I recognize that these proton pump inhibitors, for instance, and to a lesser extent H two antagonists, these types of medicines, they basically knock out the ability of your stomach to produce acid. And so when you do reflux and material comes from your stomach and gets up into your esophagus, it might not burn as much. And about half of the people with reflux get symptomatic relief from those types of medicines. Half don't. But the real issue is why are you refluxing? That's what you need to address. Because it's not just acid, it's stomach enzymes, pepin, it can be pancreatic enzymes when they look they find bile, right? Bile is something, it's a caustic molecule. (11:50): Your liver produces these bile acids stored in your gallbladder, released into your small intestine to help digest fats. And all of these other functions are antimicrobial. But when they reflux back into your stomach and then into your esophagus, they're caustic as well. And the proton pump inhibitors won't do anything about those. And then on top of it, this long-term health consequences of removing your stomach acid. Mm-Hmm. , you may very well have not absorb vitamins like vitamin D, certain B vitamins, B12 because your stomach makes intrinsic factor that that is needed for B12 absorption. You might not absorb iron as well. Magnesium in particular, in fact on proton pump inhibitors, there have been cases with this hypomagnesemia low blood mag magnesium, which is a dangerous condition, cardiovascular metabolic health and even supplementing with magnesium doesn't always correct the issue. So there are long-term consequences of these drugs. And when I work with people, there may be a reason they need to be on a PPI to begin with. Say they have gastritis or an ulcer. Well that is one instance where those can be helpful, but the goal should be really healing that and then giving reflux under control and then getting off of these acid reducing medicines. I've worked with people that have been on them for 20 years. It's a problem at that point. (13:19): Yeah, it's, I think they're really only approved for short-term use, but doctors put people sometimes on these who are taking them for years and it just decimate the rest of your digestive tract, which affects your hormones. Ladies (13:35): . Yeah. And your microbiome. There's a number of studies saying that, that reducing the stomach acid on these drugs drives changes in your microbiome. So natural is always the best whenever possible. , that's my motto. (13:50): So we can't talk about the microbiome enough. We've talked about, you know, how would I know if I had a functional gut disorder? Well actually let's go into this next. What type of evaluation should people be expecting to have if someone really is doing a root cause resolution approach and looking at why they have a dysfunctional gut issue, what kind of testing is available and should they look for an ask for? (14:13): What I routinely use in, in my consultation practice is comprehensive stool analyses. Now those results won't necessarily tell you whether you have sibo. All right. Small, an overgrowth of bacteria in your small intestine. It's really looking at the composition of your stool. However, first of all, there are many types of dysbiosis. SIBO is one of them. There's also cifo, small intestinal fungal overgrowth. There's libo, what I loosely call libo for an overgrowth in urological biological intestinal overgrowth. And it's based on a couple of studies that are very convincing that you can't have an overgrowth in the early part of your secum and large bowel as well. Mm-Hmm , you can have these methanogens overgrowing that's called imo, forint intestinal methane overgrowth, people that are making too much methane. But you can also have significant imbalances in the composition of the gut microbes in your lo intestine. (15:11): Right. And when you have that, what are the ramifications of that? So in these stool tests, first of all, you're going to look at a lot of other digestive markers. You're going to look at elastase, which is an enzyme produced from the pancreas. That is an important test. A lot of doctors use just that test itself to determine whether the pancreas is functioning and release, releasing other important digestive enzymes like amylase, lipase and protease. Elastase is just the test they use to assess the pancreas. You're looking at S I G A, secreted immunoglobulin A. In other words, how's your gut immune system doing? I G A is important for gut barrier integrity, for balancing the good and bad microbes. You're going to look at a whole variety of pathogens that may be your problem, right? You can roll in certain other testing, helico, pyuria, bacteria, infect stomach, clostridia, difficile, especially if somebody has chronic diarrhea. (16:14): But then you also look at all of your, what I call commensal populations, right? The bacti, the firm acutes the proteobacteria on and on, right? A number actinobacteria bifidobacteria. And then you wanna know what do your populations look like in each of those high level and detailed species level breakdown compared to kind of the healthy consensus population. And so it takes a trained eye to really go through these tests, but there's a lot of actionable information in there when you do that. So for instance, what I like to see right off the top, I like to look at the firmicutes and the bact ADIs because those two Fila rep like and Utes are like bacillus and strap. And some of those species, lactobacillus, those are all Utes, bact, ADIs, that's bact, fragiles, bact theta, ITO micron and so forth. They're highly diverse, these two Fila. (17:16):And they represent 90% of the microbes in your gut, just these two Fila. And so the ratio of those is really important. If you have a lot of these firmicutes over the BDIs that's commonly seen in I B s, it's commonly seen in epilepsy, it's commonly seen in obesity. And it's also common on a plant-based diet. If you eat a lot of plants and your digestion is working well, you may have too many of these firmicutes on an animal-based diet. There's more of the BDIs. And also that's more indicative when somebody is addresses i b s or addresses obesity or addresses the epilepsy. You see that shift. So there's just so much to look at in these comprehensive stool analyses, but there's some of the highlights. Yeah, it's very false. (18:06): Yes. And I'm wondering if you can speak to the utility of, I'm not sure if you look at this cuz you come from it, gut health from a microbiology standpoint, but food sensitivity testing. And then if you could comment on, are these types of tests that your regular H M O doctors going to order and know how to read? (18:26): Mm-Hmm. Yeah, that's a good question. Not all of them. Although if you go to certain websites of some of the companies that do this test, like Genova, they have a GI FX test, very good test. I use it often. If you drill into their website, they will point you in the direction in your state to doctors that routinely have accounts with them. You know, for instance, our Digestive health Institute has an account with direct labs, so we can get the test that way, but they'll point you in the direction of doctors that can order these tests. And you brought up an important point. You mentioned food sensitivities and while we're at it how about just kind of inflammatory conditions? Mm-Hmm. . And there are markers in this same test that look at that. For instance, calprotectin. Calprotectin is a protein released from activated white blood cells at the site of inflammation. (19:17): And so if you have high levels of calprotectin, you're in an inflammatory state. Now it might be just a couple of hundred and okay, that's still high and you need to address it. But somebody with inflammatory bowel disease for instance, they might, might have levels. And I think the units are micrograms per gram of 2000. So it can tell you a lot. Now in terms of food sensitivity, there's EO eosinophil, protein X mm-hmm . And that's considered a marker of kind of food sensitivity. So that's another one you can look at. You can look at lactoferrin, you can look at if there's microscopic signs of blood in your stool because that's another sign potentially of inflammatory bowel disease or even colorectal cancer. So there's a lot in these tests and it's a really good thing to do if you have a lot of gut issues and, and you need to try to understand why and what to do about (20:14): It. Yes. So I love these tests. I usually use the GI map, that's my favorite. It gives a lot of those markers that's, and you know, I was thinking earlier when you were running through the different species, the bacteria, some people will get tripped up thinking they have to know all these different names. I mean it's helpful if you do, but it's kind of like your friends at church that maybe you know their face but and you wave high, but you might not remember all of their first and last names. You don't need to. So don't feel like it's something that you have to memorize if that trips you up. But you can just learn the ones that are most important. Just like in your communities where you have friends who you know their first and last name, you know where they live, you know their phone numbers. (20:56): So it's a similar type of community. So consider if you are a candidate for functional gut testing, having some of these tests, food sensitivity is something that I, I really recommend. I don't think there's a perfect food sensitivity test, but I think they all have their pros and cons. So you kind of have to, whoever you decide to work with, I do think having a guide with these types of things is very helpful. Pick which one could work. So tests, don't guess get an evaluation. What are some of the common things that we can do though maybe we can't afford testing. This testing is not inexpensive. I know. Mm-Hmm. , you know, the GI effects with Genova and the GI map or $500 or more. So not everyone can afford that. So what are some steps that people who are having functional issues with their gut might mm-hmm. just start to take from a general basis that could impact how their gut is functioning. (21:57): Yes. In fact, you can do a lot. In fact, I'll usually start, if there is some testing, especially GI testing or say a SIBO breath test, I will like people to get those samples done before they start kind of some interventions. But oftentimes we'll just work by just taking a complete history of somebody, you know, how long has this been going on? Exactly what are your symptoms, what is your diet like? Is really an area that I dig deep into because I work with people that have very varied dietary preferences. I work with vegetarians, pescatarians, mostly omnivores, but a good number of vegetarians and pescatarians and once in a great while of vegan as well. But it matters because we had talked about this molecular food chain, right? When you consume food, right, it consists of proteins, fats, and carbohydrates, right? Those are the three food groups. (22:54): And while the microbes in our gut can utilize some of the amino acids from proteins for energy, there are some bacteria, these sulfate reducing bacteria for instance, that no tricks how to get energy from fats. It's not a high energy deal, but they can do it. But the microbes in our gut get most of their energy from carbohydrates. So if you're on a plant-based diet, you are consuming a lot more carbohydrates. And the five that I really focus on, and I look for when I, when people tell me what they're eating is fructose and lactose. Two sugars that tend to be difficult to digest, to absorb. And in the case of lactose digest with lactose intolerant people, but also resistant starch fibers and there's a huge variety of fibers and sugar alcohols. There's many sugar alcohols difficult to digest, but yet all of these are fermentable by microbes. (23:51): And by the way, there is one kind of gut-friendly sugar alcohol called erythritol that won't drive these overgrowths and all this gas that we've talked about, but the other species can, if you're not digesting and absorbing these foods, well in fact we don't digest fiber by definition that you can overfeed these microbes. And there's a common belief these days that we're actually starving our microbes, that we need to eat more fiber and more fermentable material. More of these five types that I mentioned. I reject that if somebody's perfectly healthy and they're not having any of these GI issues, okay, I won't, I won't chime in, but for people that are having a lot of gas, altered bowel habits, bloating, all of these symptoms, I will really look closely at their diet and then focus in on their digestion and say, what, what's wrong here? Why are these microbes being essentially overfed in your case? (24:47): And so it gets to kind of the mechanistic part of it. And so if you had to break down the fast track diet, that's a diet I created. I've written a couple books on it or my consulting practice, I always focus on these three important areas, diet and digestion, right? What are you eating and is that diet matched with your ability to digest and absorb those nutrients efficiently or is there a, a mismatch? So diet and digestion is big. And then the next part is root cause analysis, right? What are these potential underlying or contributing causes? As many of these, you know, probably a hundred if you consider the rare ones, but 25 or 30 or 35 are relatively common and they won't be common to everybody. So we have to, in most cases rule most of them out to really focus in on what is the most likely underlying cause or causes in that particular case. (25:45): Cuz it's somebody that has hypochlorhydria, low stomach acid and there's all these risk factors and reasons for that. Is it somebody that has pancreatic insufficiency, right? We talked about the elastase test to measure that. But even if you don't it say you can't afford the stool test, you can just try a digestive enzyme that contains pancreatic enzymes. And the same goes with these brush border enzymes, these disaccharides, lactase, sucres, maltase, iso, maltase tris, it's many of them. They can be damaged on the brush border. It's not easy to get that test done. They usually use that test for kids with genetic deficiencies in these enzymes because it's a very dangerous condition. But we now know in adults with these functional GI issues, I, I'm using the term too dysfunctional GI conditions, right? , they, it's very common for them to have these brush border deficiencies. We now know very recent work up to 70% or more have these deficiencies. (26:44): Testing requires endoscopy, taking biopsies, send it to highly specialized labs, probably expensive. But instead there are also digestive enzymes you can get that have brush border enzymes. So these are kind of workarounds. You can say, well this testing is too much, it's too involved. Instead I want you to try this particular dietary supplement that has either the pancreatic or the brush border enzymes and let and of course modulate your diet. I almost always recommend people to significantly reduce their overall levels of carbohydrates. Any more proteins and fats for the reasons I stated that those are less invasive or less li likely to drive overgrowths and dysbiosis. So reduce the carbs and then reduce in particular these five types of carbs I mentioned. And if you have a brush border deficiency, even the easier to digest starches may be a problem. In the fast track digestion books, I I break down starches into two groups, resistant starch starches that have more of a starch called amlo. (27:53): It's harder to digest or le or less resistant star, which has more amylopectin, an easy to digest species of scotch. So jasmine rice and sushi rice, it's an easier to digest scotch, uncle Bens and wild rice and bosma rice, more of the resistant scotch. So I'll say, well if you're going to have starches stick with jasmine or sushi rice, I'll, I'll add some particular name brands that I like and cook it properly in a rice cooker if possible with plenty of moisture. And then limit your serving size, right? When you cut your serving size from a cup down to a half a cup, you cut these fp points that it's a calculation I created in the book to measure how much of these fermentable carbs you're consuming on whole. When you cut your portions in half, you cut these points in half and you cut your symptom potential in half. So I'll say eat less, follow these particular behaviors and practices or just avoid starches for the next month until we really get to the bottom of this. (28:55): Yeah, I, you know, and when from a hormonal perspective, when you're saying sushi rice or jasmine rice, those are white rices, I'm thinking immediately, oh that's gonna mess up your insulin. Don't do that. Just don't eat it . No, but I hear very good point. I hear what you're saying looking at, yeah, right. So we've always gotta consider, you know, gut health with hormones and then hormones, he hormone health with gut health. And I think when we neglect one, we neglect to think about the other when we're, we're addressing one part that we can cause more problems. But yeah, so diet is super important. Sometimes you just can do empiric treatment if you can't afford testing, you can try a brush border enzyme or try adding retain and Pepsis. And I remember when I worked at the, the clinic in Atlanta, you know, getting at what is your stomach acid level? Do you have hypochlorhydria is really hard. Although most people over 30, and especially with each advancing decade, we increasingly have it till when we're in our seventh decade almost all of us have hypochlorhydria, meaning not enough stomach acid. So we actually had a Heidelberg machine (30:05): , huh, wow, good for you to (30:08): Test, right? Like who has (30:10): That's (30:10): Impressive Heidelberg machine. (30:11): Yeah. (30:12): Right. So some people are listening, you're going, what is a Heidelberg machine? So like I said, getting at a measurement of your exact stomach acid level is very difficult. But with the Heidelberg machine, you swallow a capsule and then it radio transmits the pH level to a de sensor outside and you get a computer readout of how your stomach acid changes over time in response to certain things. And it's this beautiful test. But like I said, you don't really need that test. If you're over 30, you probably have some degree of hypochlorhydria. You have gerd, you definitely do. If you've been on a P P I, you definitely do. So sometimes you can just treat empirically as that kind of, what is your approach to stomach acid disorders? Mm-Hmm. . (30:56): Yeah, no, that's very good. And I, I wanna get into that, the Heidelberg and also risk factors for low stomach, but just wanted to comment on something you said earlier. Yeah, you bring up a very good point about, okay, the, the rices I mentioned that are less problematic for your digestion also going to raise your blood sugar more, right? They're higher glycemic index, right Rices, right. The bosma and Uncle Bens is a lower gi, lower glycemic index and higher FP and the jasmine rice and sushi rice, a higher glycemic index, higher gi, but lower fp. So they're easier on your digestive tract. If you have, you do need the brush border enzymes though, which complete the breakdown of starches. Amylase doesn't do all of it. You need the brush border enzymes as well. But let's assume they're working. And so Jasmine rice is a good fit for you in terms of your digestive wellbeing, but it, it is going to raise your blood sugar. (31:47): And that's a point I do bring that up in my book. And that's one of the reasons we also recommend smaller servings of high GI, low FP foods because they will raise your blood sugar and the last thing you want to do is get into a situation with metabolic disorders or pre-diabetes or even diabetes, you know, insulin related illnesses. So we're very cognizant of that. So we know there is that trade off and so I'm glad you brought that up. Regarding stomach acid, this is really fascinating and I, I agree with you. Some people will just kind of say, well you're on a P P I when you get off the P P I, we're gonna make a lot of changes in dietary and behavioral changes get you off the PPIs and hopefully your stomach acid will pump back. Might be that simple. But for a lot of people they could have significant issues. (32:33): They may have pernicious anemia. It's an autoimmune condition where your own antibodies are attacking these parietal cells that produce the stomach acid, right? And you wanna know about that if you have it. And of course you may also have low B12 levels because intrinsic factor is needed for absorption of b12, a Heidelberg test. And it's just fantastic that you once had one. I too bad. You can still have it. You can. I just received one of those test results this morning from one of my clients and was going through it. It's an amazing test. But before I recommend that to somebody, I really do look at the risk factors for hypochlorhydria and there and there's some risk risk factors for hyperchlorhydria too. Too much stomach acid. Mm-Hmm . But I look at whether they have had an endoscopy before. If they have gastritis, that's a big risk factor. (33:22): And often gastritis is caused from a chronic infection with this bacteri helico back to Pylori. And so I wanna make sure they've been tested for helico back to Pylori. You can get it in a stool test, there's a breath test for it and so forth. I wouldn't recommend the blood test because that will just tell you whether you've ever had it. You wanna know whether you have it. So gastritis, whether you're h pylori positive or negative. If you abuse NSAIDs, non-steroid anti-inflammatories like aspirin and ibuprofen, that's very irritating on the stomach. Can lead, can lead to gastritis if you had Hashimotos, right? Hypothyroidism, autoimmune hypothyroidism, you're at greater risk for pernicious anemia. And so there's more of these. So working through these risk factors, I can usually reach a point where I can say, you know what, you're at very low risk for hypochlorhydria, let's move on. (34:11): But if the answer comes back and says you're at a moderate to high risk for it, we might either take some action steps or let's look for a place near you, a practice near you that has the Heidelberg. So it's just, it's great you brought that up. And when you go to the Heidelberg website, I forget what the name of the website is, but if you just google Heidelberg acid test, you'll see the website. They do have by state places that still do the tests so you can find them. I'm really frustrated that every teaching hospital in every state doesn't have the ability to do this because for people that that aren't familiar with the test, you are not just measuring whether somebody has acid or not in their stomach, as you mentioned. You take this capsule, you swallow it, but it dangles on a string and they, and by the pH right, it radios up to a laptop and by the pH being really low you can see, okay, you're in the stomach and that's, they might put a piece of tape there and you know it's sting in the stomach. (35:08): But the secret to that test is you can now tell what your stomach acid is and that capsule isn't going anywhere and they give you these drinks of sodium bicarbonate. Mm-Hmm That will raise the stomach acid back closer to neutrality six or six and a half, seven. And then they see how long it takes for your parietal cells to produce enough stomach acid to lower the acid back down to between pH one and two very acidic. And if it takes a real long time, then you may be diagnosed with hypochlorhydria. Now if it does it in 10 or 15 minutes, okay that's okay. But then they'll give you another drink and then once the stomach acid regains itself, they'll give you another drink, three or four of these. And so you can see if your stomach can reas acidify each of these times. If you end up with a space of about 40 or 50 minutes or an hour, then that might indicate that you have hypochlorhydria, your stomach just isn't able to keep up Reac acidifying itself. (36:06): Yeah. And you know, after I was so excited to get to work with this machine, but I have to say after, you know, hundreds reading hundreds of these tests, I've never seen one in a human over 40 who wasn't having health problem, who was having health problems that wasn't abnormal. So I do think it's (36:25): A great test. Well I seen, I've seen both and I've, I had one client that we suspect that he had low stomach acid. He was actually a hypers secret (36:32): Secret, very interesting. (36:33): Five minutes every time just making right stomach acid. So, and that can happen if you have dysregulation of gastro producing cells in the lower part of the stomach, which when those are expressed to stimulate stomach acid, they stimulate histamine release and that binds to the bridal cells and drive stomach acid. So there are a lot of possibilities that you pyloric sphincter in how healthy that's working can allow reflux from the small intestine back into the stomach that can throw off stomach acid results. So there's a lot of things to consider. It can be a little bit complicated, but I still think it's a great test right to look at in some cases. (37:14): I do too. I wanna tie everything we're kind of talking about together with hormones for everyone because I know some people are still wondering K Kiran, why are you always talking about poop , we're supposed to talk about hormones so I just wanna tie it in as succinctly as I can. But your gastrointestinal tract is actually your biggest interface with the external environment. I know it's on the inside of your body, but you're taking the external environment and you are putting it inside of you. The surface area of your gut is as big as two doubles tennis courts, which is way bigger than the surface area of your skin. So everything you take into your mouth is contacting you. So it being the biggest contact with your external environment, it is the highest concentration of your immune system designed to protect you. It's your body's military all along your gastrointestinal tract. (38:09): And that is directly related to your cortisol. Stress hormone is directly related to your immune system function is directly related to your gut function. So if your gut isn't right, your immune system's not gonna be right and your cortisol's not gonna be right. And your cortisol, I call her queen cortisol, is going to wreck havoc with your sex hormones. So you might have PMs heavy painful periods and you think all you've got is a period problem. No, you could have a gut problem or it's gonna wreck havoc with your thyroid hormone and you think you've got a thyroid problem cuz then you're overweight and tired and you don't have a primary thyroid problem, you actually have a gut problem. So if you listen to me long enough, you know what I'm talking about. If you're still scratching your head going, what in the world is she talking about? (38:55): Keep listening, come meet me on social media, join one of my challenges, we will get you up to speed on why your PU poop is good. Poop is essential to hormone health. Thank you Norm for furthering the understanding for everyone today in a very deep and meaningful way about functional or dysfunctional gut disorders. Before we wrap up, I wanna just ask you a couple things. The first is you shared a couple quotes with me before we started that I absolutely love and you said from Benjamin Franklin, whom I love the best doctor gives the least medicines. Mm-Hmm , can you talk a little bit about that and then we'll go ahead and wrap up? (39:38): Yeah, well in my fast track digestion books, I use a different quote at the beginning of every chapter. So I kind of like you, I love those. And the back one is your health depends on the bacteria in your gut. So I think that sums up a lot of what we were talking about. But in terms of the best doctor gives the least medicine, I mean I've really come to believe that and I've, I've been on both sides of the fence. I spent the first 20 years of my career after graduating from school in the Fama biotech industry developing new drugs. And I like the idea of working on these difficult diseases with unmet medical needs and coming up with, with a drug or a solution that that works for these serious conditions. You know, for, and I spent 10 years just on antibiotics and they're lifesaving medicines. (40:27): I worked on the development and approval of ciprofloxin. They're lifesavers but they're also really rough on the gut. And so when I see more and more of these kind of strong medicines being used for people with these digestive health issues that I think could better be addressed by holistic means, especially antibiotics, because those are, those really disrupt the, the microbiome. It drives me crazy, but I think it's both the manufacturers that make money on the drugs, on the doctors, it's easy to prescribe something, but also patience. Well, I can just take this pill and keep eating what I want to eat. That sounds like a (41:07): Good deal . But (41:09): So when I work with people, it does take, you have to be willing to make some changes and to really look at things in a way that, you know, you may have to change your diet and change your behaviors and try some more holistic supplements. We talked about digestive en enzymes as many, many others and get away from these harsher drugs. So that's what that means. So first chapter of that fast track digestion, i b s book is all about the drugs for i b s and the conclusion at the end of it is it's a big fail. They, they're terrible and so we need to find a different way. (41:42): Right. Awesome. Well everybody, norm is giving you a free copy of his hashtag Diet 1 0 1 ebook. We will have the link in the show notes, so definitely encourage you if you have dysfunctional gut issues to download that and read that. Tell everybody where else they can find out more about you and the work that, that you do. (42:02): Sure. Every aspect of our work and also our consultation services, blogs, information about the fast track digestion books is one on i b s and Hot Burn. The Fast Track Diet mobile app I haven't really talked about. But this mobile app is, is just the greatest way to implement the diet. It uses this FP calculation and so there's, it's got a database of over 1200 foods and their FP values and a calculator to calculate this fp value for foods that might not be on the list. So those resources can also be found in the same place. Everything can be found@digestivehealthinstitute.org. (42:40): Awesome. Well, I invite everybody who is interested to go and check that out and get that valuable resource. Thank you so much, norm for this deep conversation, deep dive into functional gut issues and what to do about them. (42:54): Well, thank you Karen. Good questions, (42:56): And thank you all for joining me for another episode of The Hormone Prescription with Dr. Kyrin. Hopefully you've heard something here today that will be impactful for your health and your life so that you can make changes to move you towards the brilliant health that you deserve to be experiencing if you are not there yet. Stay tuned. Next week I will have another wonderful guest and episode helping you better understand your health and your body from a functional approach and how to improve it. And I'll see you again next week. Until then, peace, love, and hormones, y'all. (43:30): Thank you so much for listening. I know that incredible vitality occurs for women over 40 when we learn to speak hormone and balance these vital regulators to create the health and the life that we deserve. If you're enjoying this podcast, I'd love it if you'd give me a review and subscribe. It really does help this podcast out so much. You can visit the hormone prescription.com where we have some free gifts for you, and you can sign up to have a hormone evaluation with me on the podcast to gain clarity into your personal situation. Until next time, remember, take small steps each day to balance your hormones and watch the wonderful changes in your health that begin to unfold for you. Talk to you soon. ► Free Fast Track Diet 101 ebook from Dr. Norm Robillard - CLICK HERE ► Hormone Balance Bliss Challenge by Dr. Kyrin Dunston Are you struggling to find the right solution to get your hormones and metabolism back in balance? If you're feeling like nothing is working, it's time to try something else! Our Hormone Balance Bliss Challenge was designed specifically for those who are looking for a long-term way out of their hormone and energy struggles. We'll help you understand what doctors aren't telling about how hormones affect weight gain, energy levels, and overall wellbeing. 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Thank you for joining us for our 2nd Cabral HouseCall of the weekend! I'm looking forward to sharing with you some of our community's questions that have come in over the past few weeks… Anonymous: I wrote in on FB and your support email and was referred to ask here. Can you tell me why the Omega 3 capsules and liquid has different EPA/DHA ratios and the liquid has added DPA. What would be the reason a person would select one option or the other besides not wanting a capsule or liquid? Rani: I have searched the podcast archives and haven't found anything on this topic so I was wondering if you could touch on it. Could you explain the reticuloendothelial system (RES)? Specifically the iron recycling system. I see many practitioners talk about the iron recycling system & how supplementing with iron is unnecessary and possibly dangerous. I would love to get your explanation on this topic. Thank you as I value your knowledge and wisdom. Samantha: Hi Dr. Cabral, Thank you for your time. 10 years ago I had what I thought was painful dermatitis/eczema on my hands, but looks like Chilblains. 2 years ago, my family and I found out we had mold toxicity and are still working through protocol with a functional practitioner (my suspicion is years ago, chilblains was my first symptom from an overactive immune response due to the unknown ongoing mold exposure). Do you have any insight on what root cause(s) is for chilblains and if it's related to histamine and what can be done to heal from the disease, not just manage it. Thank you, Samantha Alicja (Ah-leets-yah): Hi Dr. Cabral, My question today is about protocols and sleep. I started CBO protocol and my sleep got worse. Every day when I took CBO supplements I woke up between 3:00-3:30 am. When I'm up at this time - there is no chance for me to go back to sleep. I took a break from the supplements and my sleep went back to normal. I'm not sure what that means. Meantime I got my stool test results that detected one protozoa (Entamoeba coli) so I decided to do parasite protocol. The same thing happened. I started taking supplements (Para Support) and I started waking up between 3:00-3:30am. What do you think is happening? Any thoughts how to work around that? I need my sleep for proper healing. As always I appreciate your help and thank you greatly! Alicja (Ah-leets-yah):One more question: My test results also showed I have very low levels of pancreatic enzyme: elastase. (It should be more than 200 ug/mL and I only have 28) I take digestive enzymes with every meal. Is there anything else I could do? Do you think HCL would be better for me? Or should I take HCL together with digestive enzymes? Is low elastase reversible or most likely I'm gonna be stuck with low numbers for the rest of my life and rely on digestive enzymes for the rest of my life too? I would love to hear your thoughts. I trust your knowledge very much. Thank you for you your amazing work. Summer: Hi Dr. Cabral! I'd love to hear your thoughts on plant based protein powders. I don't know if I can use actual company names or not, but I've used Genuine Health and Sun Warrior over the last few years and I notice that I CAN tolerated plant based protein in a powder but CANNOT tolerate most plant proteins in whole food form. Looks like both companies are calling their products fermented which also raises a couple of questions. I know you suggest cutting anything fermented if you have gut dysbiosis, but how could any of those ‘good healthy' fermented bacteria survive the processing required to make these powders? So is it necessary to cut these powders with gut dysbiosis? Is the purpose of the fermentation in these cases meant to purely break down the plant into a more digestible form rather than trying to use it to repopulate the gut with good fermented bacteria as you would do with homemade ferments like sauerkraut? I can understand that it might help break down the plant, but I don't see how any good bacteria would ever survive that processing. Thanks so much, and have a great day! Thank you for tuning into this weekend's Cabral HouseCalls and be sure to check back tomorrow for our Mindset & Motivation Monday show to get your week started off right! - - - Show Notes and Resources: StephenCabral.com/2347 - - - Get a FREE Copy of Dr. Cabral's Book: The Rain Barrel Effect - - - Join the Community & Get Your Questions Answered: CabralSupportGroup.com - - - Dr. Cabral's Most Popular At-Home Lab Tests: > Complete Minerals & Metals Test (Test for mineral imbalances & heavy metal toxicity) - - - > Complete Candida, Metabolic & Vitamins Test (Test for 75 biomarkers including yeast & bacterial gut overgrowth, as well as vitamin levels) - - - > Complete Stress, Mood & Metabolism Test (Discover your complete thyroid, adrenal, hormone, vitamin D & insulin levels) - - - > Complete Food Sensitivity Test (Find out your hidden food sensitivities) - - - > Complete Omega-3 & Inflammation Test (Discover your levels of inflammation related to your omega-6 to omega-3 levels) - - - Get Your Question Answered On An Upcoming HouseCall: StephenCabral.com/askcabral - - - Would You Take 30 Seconds To Rate & Review The Cabral Concept? 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Puanani Hopson, D.O., a Mayo Clinic pediatric gastroenterologist, explains the pancreatic elastase test — a screening test that can be useful when symptoms point to the possibility of exocrine pancreatic insufficiency. Dr. Hopson reviews when this test should be ordered, how it compares to other test options, and how its results can guide further evaluation.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.06.371534v1?rss=1 Authors: Ghosh, D., Bansode, S., Joshi, R. S., Kolte, B., Gacche, R. Abstract: The serine protease, elastase exists in various forms and plays diverse roles in the human body. Pharmacological inhibition of elastase has been investigated for its therapeutic role in managing conditions such as diabetes, pneumonia and arthritis. Sivelestat, a synthetic molecule, is the only elastase inhibitor to have been approved by any major drug regulatory authority (PMDA, in this case), but still has failed to attain widespread clinical usage owing to its high price, cumbersome administration and obscure long-term safety profile. In order to find a relatively better-suited alternative, screening was conducted using plant flavonoids, which yielded Baicalein, a molecule that showed robust inhibition against Pancreatic Elastase inhibition (IC50: 3.53 micromolar). Other than having an IC50 almost 1/5th of that of sivelestat, baicalein is also cheaper, safer and easier to administer. While Microscale thermophoresis validated baicalein-elastase interaction, enzyme-kinetic studies, molecular docking and molecular dynamic simulation revealed the mode of inhibition to be non-competitive. Baicalein exhibited binding to a distinct allosteric site on the enzyme. The current study demonstrates the elastase inhibition properties of baicalein in an in-vitro and in-silico environment. Copy rights belong to original authors. Visit the link for more info
Ken Brown 0:00 Welcome, everybody to gut check project, Episode Number 39. A super cool one because my co host is also our guest, the expert, the person that we all love whenever Eric goes out of town on a mountain biking expedition, which is what he's doing right now. So we have the super smart, super well trained Dr. Stuart Akerman as both our expert guest and our host, Dr. Akerman, thanks for coming.Stuart Akerman 0:27 Ah, thanks for having me here. I was more than happy to pay for Eric's vacation so that I can do this.Ken Brown 0:33 You are pretty sly like that. That's pretty interesting. You're sort of, you're sort of pushing him out. And so I think that's, you know, he thinks he's having fun. Stuart Akerman 0:41 I made him think it was his idea. I mean, that was really what came down to.Ken Brown 0:46 Well, in today's episode, this is really cool because when I said that Dr. Ackerman is both the co host today and our expert is because we're going to tackle a topic that a lot of people have and it is diarrhea specifically related to something called a epi exocrine pancreatic insufficiency and you're like, Huh, I saw a commercial on that. What's that? Exactly. That's what all my patients say. They're like, what is this? They come in and talk about this. So usually whenever Eric and I before we start, Dr. Akerman, what is going on with you and the Akerman family anything personal you want to share?Stuart Akerman 1:20 Yeah, could share all kinds of things. It's been definitely interesting. And the quarantine life as we now gear up at the end of the summer trying to figure out what do the kids kids are sort of excited to go back to school not sure what they're going to do, but I never thought they'd have this problem that they've actually watched all there is to watch on TV and they need something else to do.Ken Brown 1:44 That reminds me of I think I saw some funny video where somebody was sitting in front of in front of his computer and it goes, you've done it. You've reached the end of the internet.Stuart Akerman 1:54 It's kinda like that. There's nothing. You only have so many subscriptions, I guess.Ken Brown 1:58 Exactly. Yeah, well in the brown household. I took Lucas to a tournament pretty cool. in Wichita Falls, it was a well run tournament. So kudos to the tournament director out there. It was a college tournament. So Lucas out, unfortunately lost in a tough third set tiebreak to a really good player. And you know, we just kind of move on. And we got so excited to talk about what he learned from that. And then by the time we got back to Dallas, they had canceled the national tournament, which is why he was doing this to prepare for the next one. And so we're dealing with that where we try and make plans and keep these the passion up. SoStuart Akerman 2:37 And you know, when we were talking the other night, I actually realized after we hung up that I wanted to ask Lucas, I mean, I know that it's a junior tournament. So there's no betting and things like that. But there must be some sort of handicapping system right because they are rankings. Where was he ranked in comparison to this kid who's several years older than him? Ken Brown 2:58 Well, this was actually a college tournament. So it was for college players. And so he's 15 he played a 21 year old and actually they're just on ranking level is they were both on par so the two he's Lucas was the number one seed in the tournament. And that man was the second was the number two seed so it worked out perfect the bracket got the what I consider the two best players to play in the end. And funny you bring that up because him and I were in Panama right when COVID hit because we had to bust out a Panama he was doing what's called an ITF. And I happen to have a friend there in Panama who lives there and has been doing sort of digital marketing and all this stuff. And he was running a betting website. And he goes it's not he goes people from around the world will bet on anything. And then we started talking tennis and he goes the most rigged sport, like for betting where people like there's all kinds of junior level sports that people bet on because they know that they can kind of tilt the odds one way or the other.Stuart Akerman 3:55 Oh my gosh.Ken Brown 3:56 There's yeah, it was a whole new world for me. So like when you say that I kind of cringe because I was Just like oh, no, you know, we've got we're going to start like hustling you know peewee baseball and stuff like that.Stuart Akerman 4:07 I thought I thought about how he took a, you know, someone who's I think five years or six years older than him to the brink and almost beat him. Ken Brown 4:15 Yeah. Stuart Akerman 4:16 But has such a competitive spirit to be upset by that.Ken Brown 4:20 Oh, totally upset, like, on the way home just, you know, I had two match but he had two match points. I had two match points. I just, I just would have you know, I'm like, I know. I know. It's, it's life and what's really cool is that you know, you move on and do that. So I apologize a little bit if I'm a little nasally. I do not know what blew into town, but it is killing my allergies today. So and I, it's not COVID I smell great. Also two things. I don't smell great. But I can still smell things. Stuart Akerman 4:48 Smell things Ken Brown 4:49 Smell things. So let's get back at this. So before everybody's like, well, they're just gonna talk about their family the whole time, I want to reiterate something so we stole Dr. Akerman four years ago, three years ago. Stuart Akerman 5:01 Five years ago. Ken Brown 5:02 Holy cow time passes fast. We stole him from New York because he is a specially trained expert in advanced endoscopy. So he does the things that most of us have not been trained in. And a lot of that involves the pancreas. So you and I got to talking and we had a patient recently who showed up to have her endoscopy done and she said, Hey, do I have this? And I called you in and you looked at that unlike epi exocrine pancreatic insufficiency, I'm like, man, if these drug companies are spending so much time advertising for it, we better just address this head on and let's just have an episode you're a pancreas expert. I'm more of a lumenologists is how I like to consider myself and so the lumen I like colons and I like stomachs and and hemorrhoids but you are an advanced trained person that everybody if you have a pancreas call up Dr. Akerman and make sure that your pancreas is okay. So hat you know, that's what I'm saying.Stuart Akerman 5:58 Yeah, so this is definitely something that's getting a lot of press. And, you know, if you look around TV, internet, I mean, it feels like the ads are just constantly jumping at you. And it's something that it gives everyone pause that has diarrhea. And, you know, there are different estimates, but more than 5% in a conservative estimate more than 5% of the population deals with chronic diarrhea in some form. And you know, 5% is a lot of people and not everyone gets to the bottom of what's going on with them and gets that relief and that, that feeling that they know exactly what it is and how to deal with it. And for years, pretty much we knew about inflammatory bowel disease and knew how to evaluate for it and rule it out. And then there's kind of a short list, you know, all we look for what we have, you don't have any of that you probably have IBS. Ken Brown 6:51 Oh the famous, you probably have IBS, so that's my world where everybody comes says, I have IBS and if you're somebody if you're 20% of the population that suffers from irritable bowel syndrome. It can be diarrhea, constipation or mixed. And you may be one of those frustrated people that you go into your doctor, you have an endoscopy, colonoscopy and some bloodwork you get pat on the head and you go good news. It's just IBS you leave and you're still miserable. And I think that's why there's so many commercials going on here where it's like, look, maybe we're not thinking hard enough on some of this stuff, my world is SIBO bacterial overgrowth, your world is pancreas, and so that's why you're the expert on this. And so, let's do let's not make this too sciency. I know that we all you're still in the office. I love that you just got done doing telemedicine. And if anybody, doc, go to Dr. Akerman's website, set up a telemedicine visit if you're concerned about this, because he's the expert. So let's hop right in. I'm going to start interviewing you less as a co host more as an expert. So what is your standard workup? I'm gonna start from the beginning on diarrhea. Somebody comes in and said I've had diarrhea for two weeks, do you care? Do you like that you call that chronic diarrhea versus the person says I've had diarrhea for a year? Stuart Akerman 8:07 Right. So that's actually a great way to start the question because what makes something chronic? And it seems to be accepted that if it's four weeks or longer, you're dealing with chronic diarrhea. So the first thing I want to do when a patient comes in, I want to get a sense of what this means to them when they say they have diarrhea. That means 10 different things to 10 different people. And that could be part of the reason why it's so difficult to get the right workup. It's it's trying to fit a square peg into a circle hole. And you got to make sure that everything lines up. So one of the most important things to do is get a sense from the patient. What's bothering them, what does it mean to them? Are you saying you have diarrhea because your stools are loose? Are you saying you have diarrhea because you go 10 times a day? How does it work? Is it when you eat if you don't eat you're fine? Do you go no matter what you wake up five times a night to go to the bathroom even though nothing else has been going on? These are things that you can tease out that might send you along different paths in the workup.Ken Brown 9:10 And when you say tease out, that's the art of somebody that understands their craft really well. This is why we can still do telemedicine and be effective because that history, the patient history tells a story, you have become a detective. And you're going to get to the bottom of this. All those questions you just asked, are all things: have you traveled? Has this happened? Do you wake up at night? Those are all the same things I ask. So you start kind of moving to this area. So all right. So I'm going to play patient, I'm going to say I've had this for six months. I don't wake up. I use the restroom afterwards. And I just feel like I'm not absorbing things.Stuart Akerman 9:50 Right. So that is definitely a classic paradigm for epi. And, you know, I think it's important that we kind of define what that means if you have exocrine pancreatic insufficiency. I thought about it this morning. And I was trying to think about what would be a good way to explain it that would really resonate with our viewers as to how you might have epi. I think, I think the classic reason to have is you burnt out your pancreas, you have chronic pancreatitis, the pancreas is very scarred, it can't work. I think it's very easy to understand that if your pancreas is impaired in some way, that the function of it isn't going to be that great either.Ken Brown 10:32 So let me let me stop you right there because we're going to get into that in a second because we're gonna start with step one. Step one is you're a pancreas expert. Why are people using this acronym epi? Because the pancreas does a lot of really important things. It has the endocrine function, and it has an exocrine function define what those two are.Stuart Akerman 10:52 Sure. So the endocrine function is essentially your insulin. So if your endocrine function is impaired, that means You have a low insulin level. And that's actually what type one diabetes is, right? You're not making enough insulin. So the answer is how do you fix that? Take insulin, right? If your pancreas can't produce it for you, you can take it and essentially help it out. That's the endocrine side. The exocrine side when we talk about pancreatic exocrine insufficiency is related more to direct digestion of carbohydrates, fats, and to some degree proteins. And those are what are called lipases, proteases and amylases. And there are varying concentrations of each of them that are spit out by the pancreas in response to stimulus which is eating.Ken Brown 11:42 So I eat something I eat a hamburger, I've got bun, meat, cheese, eat it, swallow it. Stuart Akerman 11:50 Well, that's you. I wouldn't have cheese in there. But that's me.Ken Brown 11:54 But so we've got protein, fat and carbs and through really beautiful complex signaling the pancreas then releases these digestive enzymes.Stuart Akerman 12:04 Correct.Ken Brown 12:05 Known as the execution portion of it.Stuart Akerman 12:07 Correct. Ken Brown 12:08 Okay. So exocrine portion. So if I have an exocrine insufficiency, meaning maybe I'm not putting out enough enzyme,Stuart Akerman 12:18 Right? So either you're not putting out enough, or maybe you're not getting to the point of the bowel where you would do that, for instance, in surgical procedures that bypass the area where you would spit out the exocrine pancreatic enzymes, you'll end up with an insufficiency which essentially boils down to a mal digestive disorder.Ken Brown 12:45 So a malabsorption. So people don't are not getting these nutrients. So we've got an exocrine pancreatic insufficiency: epi. So when I do my workup, and I go, you know, Dr. Akerman, it looks like there's some unusual things going on with this patient that I think I need your assistance with. They are low on their vitamin K, their vitamin E, their vitamin D, they've got, they're describing oily stools. That is how I've been classically taught what epi is. What the commercials are saying is they're casting a broad net. They're like if you've got bloating, abdominal cramping, and change in bowel habits, ask your doctor about epi. And I'm gonna close this out as to why I think they're casting such a broad net in the end, but we're going to still talk about the physiology pathophysiology. So it sounds a lot like irritable bowel syndrome, these commercials.Stuart Akerman 13:42 Right, and and there's tons of overlap. So if I had to say, what's the single largest diagnosis or the largest swath of patients with a specific diagnosis that are going to overlap, it's going to be irritable bowel, right. You're bloated, you're gassy. You're having loose stools. You don't quite feel good after you eat. These are all signs of both irritable bowel because of a sensitivity issue when you eat, but also a malabsorptive this issue at the same time, so those symptoms alone won't quite make it. What you alluded to is someone who has fairly advanced disease so that when they eat, they really aren't producing any enzymes. So everything's going to come out in particular fat. So those fat soluble vitamins A, D, E, and K, are going to be more susceptible to deficiencies, and you'll actually sometimes see what looks like fat or oil droplets in the bowl with the stool because you can't absorb the fat appropriately.Ken Brown 14:44 Yeah, exactly. I and this isn't just an issue of a gastroenterologist when I was looking this up I got on YouTube to see like what other people have said about this. And my friend and author Rob Wolf, he, he was doing a whole thing a q&a. And that was a question. I'm seeing all these commercials coming up on this on his YouTube channel. He was like this is coming up a whole lot. And so he addressed the exact same thing and discussed the endocrine the exocrine. So shout out to him for taking that on because it's, it's clearly reaching the masses right now. So, we just want to demystify this, talk about now we know what the symptoms are, which can be pretty broad. Let's talk about some causes. So you were getting into the causes before. So let's talk about causes of what can actually cause true exocrine pancreatic insufficiency. And then we'll talk about non pancreatic causes, and then talk about diagnosis and then ultimately, the treatment. Sound fair? Stuart Akerman 15:41 Right. Yeah, that sounds great. So pancreatic causes probably the single biggest cause would be chronic pancreatitis. So chronic pancreatitis is an issue where you start laying down scar tissue within the pancreas. And, you know, it doesn't in general happen overnight. I mean, you could theoretically get a major inflammatory episode or a trauma, that that could really give your pancreas a hit all in one fell swoop. But, in general, this is something that happens over time. It's kind of like laying the groundwork and the scaffolding and eventually it keeps building up. So...Ken Brown 16:19 Why...you deal with the pancreas, you deal with pancreatitis. What is pancreatitis? And why do I care about that?Stuart Akerman 16:26 So there's two kinds of pancreatitis. There's acute pancreatitis and chronic pancreatitis, and they're not the same thing. And they're often confused and they're actually distinct entities. They can relate to each other. But the mechanisms are different. When you have severe pain, and you show up to an emergency room and they do a CAT scan and tell you oh, you got acute pancreatitis. What that means is your pancreas is inflamed. It might be swollen, there's a lot of fluid around it. It's an inflammatory process. But when you have chronic pancreatitis chronic pancreatitis means that it's scarred, it's shriveled. The word they use a lot of times is atrophied, or sometimes calcification. Now you can have both. You can have chronic pancreatitis and have a pancreas that's a little bit shriveled and then gets inflamed. And we call that acute on chronic pancreatitis and it may make your threshold to get acute pancreatitis a lot lower.Ken Brown 17:25 And people that have ever had this are nodding going, that's not fun at all. pancreatitis is a very serious issue. Stuart Akerman 17:31 Yeah, we don't wish it upon anybody. Ken Brown 17:33 No, not upon anybody. Okay, so that's what pancreatitis is. As a gastroenterologist that deals in this what, what are some of the causes of chronic pancreatitis? Actually, I think that I mean, acute and chronic, the causes are the same. It's just the repetity of insults correct.Stuart Akerman 17:52 For the most part, I'd say you know, the, the two most common causes for acute pancreatitis in America are Alcohol and gallstones. And if you continue to get like you said if you continue to get acute injury is acute pancreatitis, you're going to keep developing more and more scars as a result and you'll end up with chronic pancreatitis. I'd say one thing that has not really been shown to cause acute pancreatitis, but is very much in the conversation for chronic pancreatitis is smoking. We have patients who have chronic smoking over time. Never had an acute pancreatitis episode ever develop EPI or chronic abdominal pain and in the process of the workup are found to have chronic pancreatitis and the risk factor they have is chronic smoker. Ken Brown 18:42 That's something that I've never actually come across and do you have an etiology of why you think smoking does that?Stuart Akerman 18:48 So it's tough to say but I mean, we do know that physiologically, smoking does lead to scar it's been seen in many organs. Ken Brown 18:56 So hold on, let me write this down. So smoking is not good for you. Is that what you're saying? Stuart Akerman 19:00 I think it's something I'm pretty comfortable putting my stamp on as a physician.Ken Brown 19:04 I mean we're in a really political environment. You better feel strong about it.Stuart Akerman 19:09 Yeah, I don't know. I don't want any of the big tobacco companies coming after me. I'd say from a from a medical perspective, there's not much good that comes from it.Ken Brown 19:20 Okay. So mostly from just the inflammatory process.Stuart Akerman 19:23 It seems to be, it seems to be, but it's been it's been linked to many cancers and various organs that are unrelated to each other and chronic scar. We've seen that too the pancreas being one of them. Ken Brown 19:36 Okay, so pancreatitis of the acute can lead to chronic correct. So if you have an acute episode, you may end up with a slightly chronic one. If you continue to drink or smoke, you can end up developing this. Are there any other disease states related to chronic pancreatitis?Stuart Akerman 19:55 So there's a there's a viral states we have something called tropical pancreatitis not really seen so much in North America. More more seen in the in the eastern countries. One of the autoimmune disease. The pancreas is one of the organs that can be affected by autoimmune disease. So patients who already have one autoimmune disease be that autoimmune thyroid disease, rheumatoid arthritis or other arthritities these are always more susceptible to getting a second autoimmune disease and the pancreas and sometimes the liver are the ones that we deal with. And then actually high triglyceride levels. That's actually the number three it's a distant third in comparison to the first two but that's the third most common reason for recurrent pancreatitis is hypertriglyceridemia or high triglyceride levels and you know, I'm not talking like you know, you got a little bit of an elevation and your doc tells you that you probably should cut down on the fast food and maybe exercise a little more but significantly elevated sometimes in the thousands,Ken Brown 21:01 So my experience has been and you've seen so much more of this, but it seems like these are young people with a some sort of genetic issue and they have these hypertriglyceridemia. And it's usually really bad that first episode. Have you seen similar episode or similar findings?Stuart Akerman 21:18 Yeah. And occasionally, it's so bad that we actually have to do almost a dialysis type procedure to get the triglycerides out of their blood, just so that it stops inflaming their pancreas and they can get over it. And then from there, we can try medications to keep it down. But yeah, sometimes it's just so overworked that they're just in the throes of it and we just have to break that cycle.Ken Brown 21:43 And then last thing is that I have a large inflammatory bowel disease, population Crohn's disease, and it has been associated with that. Is that just part of the autoimmune process that you were just talking about?Stuart Akerman 21:52 Yea it seems to be that there's some some part of the autoimmune cascade there because we do know, you know, as much as we know so much about Crohn's disease. There's so much that we don't know. But it's it's fairly clear at this point that there's an autoimmune component in addition to environmental ones. And it's possible that that overlap is where the elevated pancreatitis risk comes because we do see what's called igg mediated which is another way of saying autoimmune disorders of the pancreas and bile ducts and liver in relation to Crohn's and ulcerative colitis. Ken Brown 22:26 The infamous before you arrive. Dr. Goldsmith, make sure you're checking igg four on that person.Stuart Akerman 22:32 Yeah.Ken Brown 22:32 Subtype that could potentially affect the pancreas. Stuart Akerman 22:34 There's a method to it. Ken Brown 22:36 Yeah. All right. So now I'm worried. I've got some I smoked a cigarette yesterday. I had had a drink of my buddies. I go poop and my my stool is floating. This is kind of a trick question. Is that pancreatic insufficiency?Stuart Akerman 22:55 Not necessarily. I mean, everyone's entitled to have floating poops every once in a while. More commonly, it's actually related to just some gas that's stuck in the stool and therefore it's not truly as solid as it may look. And it's floating, any kind of, you know, malabsorptive issue, even if it's transient, like something you ate that you didn't quite digest well, or maybe you had a passing viral illness can cause very similar symptoms. So the chronicity establishing that this has been going on is a really major piece of the puzzle before you go down that road to worry about it.Ken Brown 23:27 So I throw that out there because I was traveling and I got called by some men's health or something, hey, we're doing this article on stools. But we want you to comment on what is floating stools mean, so I had to like sit in an airport, you know, log into their Wi Fi and then like type this response and it was about air. And because of that I came across an article when when we were preparing for this epi that a very fun I call this my fun stool fact it's that many people believe that floating stools is related to pancreatic insufficiency or malabsorption. The reality is stools sticking to the toilet bowl have been more associated with steatorrhea or more lipid or more you're passing oil and fats. So I thought that was kind of fun.Stuart Akerman 24:09 It greases that adherence to the bowl. Ken Brown 24:11 Isn't that funny? So I have all these patients go I saw my stool floating and I'm like, okay, that's right. All right. So...Stuart Akerman 24:18 I'm curious to know what your Google searches look like now that you did that in a in an airport. Ken Brown 24:23 Oh, forget about the Google searches. You got to see the ads I'm getting. I'm being haunted by some really scary ads right now. But the good digital marketers to profile me and then track me down. So so we know what pancreatic insufficiency is. I want to know, are there some other things that can cause similar looking symptoms before I make an appointment with Dr. Stuart Akerman to really determine if I have this are there non pancreatic causes that can do stuff like this?Stuart Akerman 24:58 Yeah, and that's the idea we talk about when you see when you see any kind of provider about building what's called a differential diagnosis. So differential diagnosis being these are the, all the things in the realm of possibility might be going on. And we need to have a plan of attack to figure out which ones make more sense and which ones don't. And in this situation, you got to think about IBS, you got to think about celiac disease, you got to think about bile salt diarrhea, then there's your sort of very random ones, like neuro endocrine tumors, IBD doesn't really play in usually, in most cases, but if you have some mild Crohn's disease of the small bowel and may be essentially causing a malabsorptive problem, the symptoms might overlap. And that's where the art of medicine really comes in. You know, rather than saying, well, why don't we just test for everything and see what sticks. You really sit there and take everything into account of your patient. So that you can make a more focused differential diagnosis. How often are they going? What does it look like? Is it waking them up at night? What medications are they taking? Is there something new or different that might be causing the problem? Have they recently traveled? And you take all that into the hopper and see what comes out.Ken Brown 26:18 Now that is an absolutely great answer. So there are non pancreatic causes. So if you're having something like this, go to a very experienced board certified gastroenterologist to ask all those questions and figure out where, okay, so now the patient's seen you, you've asked the questions, you're still very suspicious. What do you do with the patient then if you're still concerned that this could be epi exocrine pancreatic insufficiency?Stuart Akerman 26:46 So nowadays, there's actually a really nice, really easy test that you can do as sort of your gateway for epi evaluation, and that's called a pancreatic elastase. It's actually a stool study. To sort of say it in a quick blunt way, if your pancreas is working, you should be making so much excess enzyme that you should be pooping it out. And we would love to test that. And basically you send a stool sample, they check for this pancreatic elastase. And your levels should be really, really high if things are working well. You should be doing so well, your your pancreatic elastase rich. But if that number is coming down, if that number is lower, that's a sign that you're just not functioning appropriately, you're not able to produce enough to meet demand. And that's where the concern for epi comes in.Ken Brown 27:40 So a couple things I love about that. Number one, you said we would love to test that. So for everybody listening, when you see a gastroenterologist, and you go, oh, I'm so embarrassed about talking about this. No, we love to hear that because when you go, doc, I don't want to. I'm super embarrassed, but when I go poop, it looks like you poured olive oil in there, I'm like, yes, do you have a picture of it? That's awesome. Let's talk about that. So when you say we love to test that, the beauty of elastase the test that researchers have figured out is that it remains essentially intact. Elastase one remains intact through the digestive process. So your pancreas puts it out and you can look at that. So when you're low, you're definitely low. It's not like your body's absorbing it. It's that it should be in the stool, one particular part of the elastase. So pancreatic elastase. That's awesome. Because for boards, meaning like when all of us take our medicine boards, they always ask the really hard questions like, hey, you're worried about chronic pancreatitis? Should you do these other invasive tests? So you've been trained in all these invasive tests, one of the few doctors in the DFW Metroplex that have I think there's just a handful or however many of you guys exist, which are the advanced endoscopists have actually been taught this stuff. So in case you're at an academic center in case you get an elastase, which is up is there ever a reason to do one of these invasive tests?Stuart Akerman 29:03 So if the elastase is up, that's normal. Ken Brown 29:05 I'm sorry. Low, yea low. Stuart Akerman 29:07 Yeah. So just to just to clarify that, so if it's up, that's where you want to be, right? Like I said, you want to be elastase rich, but if it's a low, because the most common reason for epi is chronic pancreatitis, and often on the standard cross sectional imaging studies like CT scan, and MRI, the only way they're really diagnosing chronic pancreatitis is if you have some of the signs of full blown advanced pancreatitis like shriveling of your pancreas, or calcification, so if you don't have those, it just means that you we know you don't have advanced chronic calcific pancreatitis, but it's a spectrum of disease. And we don't know if you've got mild or moderate disease just based on an MRI or CT and that's where endoscopic ultrasound comes in. Because endoscopic ultrasound where we're using endoscopy with an ultrasound probe attached to the bottom allows us to look at the pancreas from the inside sort of to get almost to...Ken Brown 30:09 Let me clarify here so you've got our standard endoscopic equipment. And on the very end, a very really cool special tiny ultrasound. So if you have ever had an ultrasound on your gallbladder from the outside or if you've ever had a baby and they ultrasound, you're taking an ultrasound inside the body which is...Stuart Akerman 30:31 And you say it a lot more eloquently than I do. I usually just say it's a endoscope with a little nubbin on the tip. That's an ultrasound.Ken Brown 30:40 Well, I mean, the reason why I think you always downplay this particular aspect but even me as a gastroenterologist, I call you up all the time and I say, hey, I've got this does this warrant an endoscopic ultrasound and I would do that with some other partners in our group, Dr. Goldsmith, Dr. Bob Anderson. People like that. I'm like, hey, I have a young man for no reason developed pancreatitis doesn't warrant an ultrasound. And the reason why I bring this up because a lot of people never talk about this. It's a very relatively safe non invasive procedure compared to other things to do.Stuart Akerman 31:13 Yeah, when I speak to patients, I pretty much tell them the risk profile is no different than having a regular endoscopy. There's no risk to your pancreas from the ultrasound waves. They're just sonic waves. So we don't have to worry that by evaluating we could potentially cause trouble.Ken Brown 31:31 Yeah. So when I see these commercials ask your doctor about epi. The next thing they should say is either I'm gonna learn about epi, or I'm just gonna send them to Dr. Akerman so that he can figure out if it's something that needs an eus or not.Stuart Akerman 31:46 Yeah, and I love talking about it. I you know, it's not to say that every single person who walks into the office and says, do I have epi. I'm going to go say, well, let's run the gamut. Let's do every test. Let's figure it out. You need an endoscopy before I can answer that, I'm gonna sit there and talk to the patient and get a sense of is this diarrhea or not? Because probably one of the more common scenarios is they don't actually have diarrhea. They might have some mild bowel habit changes, that to them feels like it's diarrhea, but you can tease out right away. Maybe it's a supplement, maybe they're taking a sugar substitute that doesn't agree with them, and they're mal absorbing it. And if by pulling that out, all of a sudden, magically, their stools are better. You know, there's not not every time is the diarrhea warranting of this large workup. But the flip side to that is patients who have carried this diagnosis of IBS for years. Well before we had good endoscopic ultrasound, well before we had pancreatic elastase and some of the other stool tests that we use nowadays, it might be that in 1995, that was the best we could do to say hey, you have IBS. And now, in 2020, we have a lot of a lot more tools at our disposal to maybe fine tune that and get them the right diagnosis and therefore a better treatment regimen that's going to make them feel better.Ken Brown 33:12 Absolutely. So I have these people that come in and we, I ask all those same questions and we go through that, did you have a significant change? Remember that some of the other non pancreatic things like bacterial overgrowth, SIBO can actually cause...also. So now this kind of comes to the point of okay, we've talked about what it is we've looked at how to diagnose it. And now I'm, I'm my question to you, because I'm obviously biased, and it's a leading question here. Why are the drug companies spending? I'm gonna say, I mean, we advertise and I know what it costs to advertise, I'm gonna say 10s of millions of dollars, saying ask your doctor about epi, why are they doing that?Stuart Akerman 33:53 Well, I mean, you know, death to leading question. You know, there's money to be made, right? Anytime. There's money to be made. But I think one of the biggest reasons is, is that it's been so low key and under diagnosed for so long that the potential for a patient base that doesn't even know they exist, is I don't want to say infinite because there's only so many people, but it's vast. So all these people who may never have been brought to get one of these pancreatic enzyme replacements, and therefore not spend money on a therapy that potentially could help them, all of a sudden, now the curtains are drawn, right, the doors are open, and they have this whole new potential patient base to help.Ken Brown 34:41 Absolutely, much like celiac disease where we said, Oh, it's so rare, and then we realize, Oh, no, we went from, you know, .04% of the population to 1%, to oh, possibly 3% and so on and so on. So I agree with that. I also did a little experiment here. The pancreas, the pharmaceutical pancreatic enzymes. which are available can be a little expensive. And that's something that I think it needs to be addressed here. Because if doctors go oh, this sounds like I think my opinion is that these commercials are drawn to say if you have change in bowel habit bloating, talk to your doctor about epi. That's a loaded question. You're telling the patient to drive the doctor and say, well, I don't know what the heck, let's try it. So on good Rx, if you pay cash, the starting dose of the major pancreatic enzymes, which are porcine and bovine derived, meaning pig, and/or cow derived, this was a little shocking to me, it's basically about averages to about $10 per pill. So if you start out the starting dose, that's going to be $2,700 a month, if you go to the maximum dose, that's going to be $5,400 a month, cash price, lots of things involved. Fortunately, we both work with these companies and they do amazing jobs of trying to give refunds and things like that. So kudos to that. I'm a little bit scared that they're going to get a bunch of doctors that knee jerk and say well try this and see what happens. That's one of my issues.Stuart Akerman 36:07 Yeah. So I do think it's important to have a diagnosis to be working with, rather than the let's throw it out them and see if it works approach, specifically for that purpose because it's expensive. But if you know that it's going to get your patient the symptom relief that they need, you're going to fight for that patient, you're going to talk to their insurance company, you're going to talk to the pharmaceutical company. They do like you mentioned, they do have robust programs for patient assistance, but that doesn't cover everybody. If you're going to them and saying, hey, I want to see if it works, it's going to be hard to justify spending $2,000 a month on that. But if you go to them and say hey, this lady has a pancreatic elastase that's super low. She's got all the right symptoms. On imaging. It looks like her pancreas doesn't quite look right. She's got mild or moderate chronic pancreatitis, this is your patient. This is the patient that's going to derive benefit from your drug. They want that because it does cut both ways. Right? You have a patient that does really well, that patient is going to tell everyone about how awesome they're doing on this drug because they got the right diagnosis. That's gonna help them just as much as any marketing they do on Facebook or Google.Ken Brown 37:26 Yeah, absolutely. Now I'm gonna ask you a question that I don't think there's an answer because I tried to look this is more of a opinion. I get asked all the time by my patients. Well, do you want me to try this I do a lot of sampling and pancreatic enzymes because I believe that there are other these extra pancreatic causes which can actually affect your pancreatic enzymes. And they will say oh, I'm already on this life extension digestive enzyme. Look, here's the label it has it says it has lipase says it has tryptase says it has amylase I have contacted them. I've contacted the pharmaceutical companies and I'm like, can you please give me a statement to define plant based digestive enzymes versus the pharmaceutical bovine and or porsine? Have you ever thought about that before?Stuart Akerman 38:17 So I have, and I can't answer it. It's gonna it's gonna sound like I'm skirting the issue. The short answer is I can't. But what I can say that I've seen with many of these, when patients come to me and say, oh, I have this naturally derived one that I'm using, very often, the amount of enzyme that they're taking is significantly lower than what we know they need. So we talk about standard dosing in the order of thousands 70,000 100,000 units with each meal. And in many of these, they'll show me yeah, I'm taking a hit. Four capsules, and each capsule has 1000 or 3000 units. So they're getting significantly under dosed. And this is not unique to say, oh, you know, plant based ones are just not quite as strong as some of the other ones that are produced by the pharmaceutical companies. I get this from second opinion and third opinion patients sometimes who say, I have chronic pancreatitis, I have pancreatic insufficiency. The enzymes don't work for me, what am I doing wrong? And eight out of 10 times nine out of 10 times the answer is really simple. You're under dosed. Because we're not trained as as as patients to think I need to take six or eight or 10 pills a day for this problem. We want the one pill or the one pill twice a day. And that's how we're conditioned to think is a standard regimen which is true of most medications. But in this situation because the problem is every time you eat you mal absorb, you need to take something every time you eat. And if we gave you the correct amount of enzyme in one capsule, you'd choke on it because it would be huge! So we got to break it down and give you smaller capsules. But it's just math. So you got to take enough capsules to give you the amount of enzyme you need with each meal.Ken Brown 40:26 That is great. That is a great answer. All right, Dr. Akerman. I think that we have taken on a pretty big topic and done it in a relatively quick expeditious manner. I want to thank you so much for taking the time. Where can people contact you because they're right now going, I have that somebody's sitting on a toilet, eating a hamburger smoking a cigarette going, it's sticking to the bowl. Oh, man.Stuart Akerman 40:50 Living life.Ken Brown 40:53 How do they find you?Stuart Akerman 40:55 So the easiest way is to go through my website. It's www.stuartakermanMD.com. And there's a an appointment tab and a contact us tab. Either one works great and my staff will get the request and contact you right away.Ken Brown 41:14 And I will say that we are part of a great group digestive health associates of Texas and we funnel or at least in this area, everyone funnels these tough cases. Dr. Akerman and you're obviously getting a great idea of his personality and he treats all his patients phenomenally but he's also endoscopically fantastic. I want to do a quick shout out once again, I mentioned him earlier but Rob Wolf, author podcaster and influencer. He, I loved that he did a whole episode on epi but more than that, I want to shout out to him because my son at this tournament in Wichita Falls, it was 103 degrees. The heat index is 110 and my son uses his lmnt element, electrolytes while he's out there hitting. So maybe that's one of the reasons why a 15 year olds taking on a 21 year old so thank you at Rob Wolf. And finally go to kbmdhealth.com. Download a free understanding your endocannabinoid system, even if you don't want to understand that the reason why is because then we can stay in touch. And you can ask questions like this like, hey, can you ask Dr. Akerman should I be worried that there's pancreatic cancer in my family? Hey, can you ask someone so we have access to experts, we can do this. Can you ask Rob Wolf, I want to do a keto diet. What do I do with this? So these are ways to stay in touch we want to interact. As always, whenever we mention anything, we're two doctors, but we are not your doctor. So this is for advice for entertainment. If you do have any of these issues, please discuss with your doctor. We are not giving medical advice. And finally, much love to everyone that listens to this, watches this. And please share, like, do a little thumbs up on wherever it's supposed to happen, like all the podcast platforms. So all in all, I think this is a great way to clarify something that has been very vague in the mainstream media. Thank you once again, Dr. Akerman.Stuart Akerman 43:13 Thanks for having me.Ken Brown 43:15 Bye, everybody. Stay safe.Transcribed by https://otter.ai
The synthesis of protease-mediated hyper inflammation in pre-morbid respiratory distress pathobiochemical states linked to coronavirus transmission . How COPD and ARDS in association with cardiovascular disease, diabetes and lung dysfunction pre-dispose to viral infection and illness. Published 11 July 2020. --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
Airway passage disease has been well characterized in cystic fibrosis and this research which involves both clinical and animal model systems can inform general respiratory distress syndrome and viral pneumonia as that ascribed to the coronavirus 19. Published 10 July 2020 --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 18/19
Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible loss of lung function and is one of the most prevalent and severe diseases world-wide. A major feature of COPD is emphysema- a long-term, progressive condition. The hallmark of emphysema includes the destruction of alveolar structures leading to enlarged air spaces and reduced surface area. Experimental evidence suggests that emphysema development is driven by accelerated senescence of lung cells but the underlying mechanism of senescence is yet to be fully elucidated. Protein arginine methyltransferases (PRMTs) are important for cellular processes, such as the regulation of senescence, cell proliferation, differentiation and apoptosis. The PRMT family includes 11 members classified as type I, II or III enzymes depending on their methylation pattern (asymmetric dimethylation, symmetric dimethylation or monomethylation, respectively). One member of this family is PRMT4, a type I enzyme, which is also called coactivator associated arginine methyltransferase 1 (CARM1). It was originally identified as a coactivator for steroid hormone receptors. CARM1 is known to methylate histone H3 and various non-histone proteins that play essential roles in transcriptional regulation, RNA splicing, and metabolism. Most importantly, complete loss of CARM1 leads to disrupted differentiation and maturation of alveolar epithelial type-II cells (ATII). Furthermore, CARM1 also plays a role in regulating cellular senescence via CARM1-dependent methylation. Based on these reports, we hypothesized that CARM1 regulates the development and progression of emphysema. To address this, we investigated the contribution of CARM1 to alveolar rarefication using the mouse model of elastase-induced emphysema in vivo and siRNA-mediated knockdown in ATII-like LA4 cells in vitro. We monitored emphysema progression for 161 days in mice treated with a single oropharyngeal application of elastase. The progression was manifested by the decline in lung function parameters. The mean chord length (Lm) confirmed a time dependent airspace enlargement and was directly correlated with a significant increase in dynamic lung compliance. We also observed that at later time points (day 56 and 161), emphysema progression was inflammation-independent. We demonstrated that emphysema advancement was associated with a time-dependent downregulation of CARM1, specifically in alveolar epithelial cells. Furthermore, the global CARM1 activity was also reduced as reflected by an elevated level of CARM1 phosphorylation in the lung. Most importantly, elastase-treated CARM1 haploinsufficient mice showed significantly increased airspace enlargement (52.5±9.6 µm vs. 38.8±5.5 µm, p
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 05/06
Fri, 6 Jun 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/18577/ https://edoc.ub.uni-muenchen.de/18577/1/Dau_Therese_Thuy_Dung.pdf Dau, Thérèse Thuy Dung ddc:570, dd
Background/Aims: Laminar shear stress is an important stimulus in the endothelium-dependent control of vascular tone and of vascular remodeling processes. Based on previous studies demonstrating integrin-mediated release of fibroblast growth factor 2 (FGF-2), we investigated whether shear stress-induced integrin activation requires the involvement of an extracellular protease. Methods: Cultured porcine aortic endothelial cells (PAEC) were exposed to laminar shear stress (16 dyn/cm(2)), whereas static cells served as controls. Results: Exposure of PAEC to shear stress led to an increased activity of a protease in supernatants. This protease could be characterized as elastase but was different from neutrophil and pancreatic elastases. The enhanced activity was accompanied by the activation of integrin alpha(v)beta(3) and p38 MAPK, and followed by an increased FGF-2 concentration in the supernatant. Pretreatment with inhibitors of either elastase or integrin alpha(v)beta(3) resulted in a reduction of FGF-2 release. The observed effects of shear stress on integrin alpha(v)beta(3) and p38 MAPK activation, as well as on FGF-2 release could be mimicked by application of pancreatic elastase to static endothelial cells. Conclusion: By inducing the release of an endothelial elastase, shear stress induces an integrin-dependent release of FGF-2 from endothelial cells. Copyright (C) 2011 S. Karger AG, Basel
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 12/19
Thu, 21 Oct 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/12204/ https://edoc.ub.uni-muenchen.de/12204/1/Egginger_Christoph.pdf.pdf Egginger, Christoph
Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 03/06
Fri, 12 Mar 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/11382/ https://edoc.ub.uni-muenchen.de/11382/1/Hennig_Theres.pdf Hennig, Theres ddc:540, dd
Background. Inhaled antibiotics are commonly used in the treatment of cystic fibrosis lung disease. A previous study suggested neutrophil elastase activation by colistin in vitro. Here, we investigated direct effects of the commonly used antibiotics colistin and tobramycin on neutrophil elastase activity. Methods. Neutrophil elastase was measured spectrophotometrically. The antibiotics colistin and tobramycin were added in different concentrations with or without the addition of albumin. Results. Generally, neutrophil elastase activity was lower in the absence of albumin compared to its presence. Both antibiotics, colistin and tobramycin, had inhibitory effects on neutrophil elastase activity except for high concentrations of colistin when albumin was absent. Conclusions. Our results suggest inhibitory effects of colistin and tobramycin in vitro. There was a clear dependency of neutrophil elastase measurements on the presence of albumin. Clinical studies are needed to investigate potential direct effects of inhaled antibiotics on neutrophil elastase activity in cystic fibrosis airways.
Robert Thompson, MD discusses the growth and inhibition of growth in abdominal aortic aneurysms through the degradation of elastin in his mouse model. (September 4, 2008)
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 03/07
Objective—To purify neutrophil elastase (NE) from dog blood and develop and validate an ELISA for the measurement of canine NE (cNE) in canine serum as a marker for gastrointestinal tract inflammation. Sample Population—Neutrophils from 6 euthanized dogs and serum from 54 healthy dogs. Procedures—cNE was purified from dog blood by use of dextran sedimentation, repeated cycles of freezing-thawing and sonication, cation-exchange chromatography, and continuous elution electrophoresis. Antibodies against cNE were generated in rabbits, and an ELISA was developed and validated by determination of sensitivity, dilutional parallelism, spiking recovery, intra-assay variability, and interassay variability. A reference range was established by assaying serum samples from the 54 healthy dogs and use of the lower 97.5th percentile. Results—cNE was successfully purified from blood, and antibodies were successfully generated in rabbits. An ELISA was developed with a sensitivity of 1,100 g/L. The reference range was established as < 2,239 g/L. Ratios of observed-to-expected results for dilutional parallelism for 4 serum samples ranged from 85.4% to 123.1%. Accuracy, as determined by spiking recovery, ranged from 27.1% to 114.0%. The coefficient of variation for 4 serum samples was 14.2%, 16.0%, 16.8%, and 13.4%, respectively, for intra-assay variability and 15.4%, 15.0%, 10.5%, and 14.6%, respectively, for interassay variability. Conclusions and Clinical Relevance—The purification protocol used here resulted in rapid and reproducible purification of cNE with a high yield. The ELISA developed yielded linear results and was accurate and precise. Additional studies are needed to evaluate the clinical usefulness of this assay.
Stress doses of hydrocortisone a re known to have immunomodulatory effects in patients with hyperdynamic septic shock. The prognosis correlates with the presence and severity of septic encephalopathy. However, neurological evaluation is influenced by the use of analgesia sedation during artificial ventilation. The objective of this study was to demonstrate the effect of stress doses of hydrocortisone during the initial phase of human septic shock on the serum values of the neurospecific protein S-100B in comparison to the inflammation markers interleukin (IL)-8 in serum and polymorphonuclear (PMN) elastase in plasma. A total of 24 consecutive patients, who met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock, were enrolled in this prospective, randomized, double-blind, single-center trial. The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation 11 and the Simplified Acute Physiology Score 11 scoring systems. Multi-organ dysfunction syndrome was described by the Sepsis-related Organ Failure Assessment (SOFA) score. All patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. Median S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/mL at study entry to 0.07 ng/mL 6 days later without significant differences compared to the placebo group. Initial IL-8 serum levels were significantly higher in the hydrocortisone group up to 12 h after study entry, and significantly decreased from 715 to 17 pg/mL at the end of the observation period. Median PMN elastase plasma levels were not affected by hydrocortisone infusion. Patients with initial S-100B serum levels >0.50 ng/mL revealed significantly higher SOFA scores up to 30 h, IL-8 serum levels up to 12 h, and PMN elastase plasma levels up to 36 h after study entry than those patients with
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 02/19
Der Tissue Factor (TF) der Gefäßwand gilt heute als der wichtigste Starter der menschlichen Blutgerinnung. Es wird davon ausgegangen, dass die Lokalisation von TF innerhalb der Gefäßwand unter physiologischen Verhältnissen eine strikte Trennung von den plasmatischen Gerinnungsfaktoren gewährleistet, so dass es unter physiologischen Bedingungen nur nach Wegfallen der endothelialen Barriere zur Bildung des TF/VIIa-Komplexes und dort zur Auslösung der Blutgerinnung kommt. Nach der bisherigen Lehrmeinung stellen Monozyten die einzigen bekannten Blutzellen dar, die nach Langzeitstimulationsbedingungen in der Lage sind, TF zu synthetisieren und zu exprimieren. Der monozytäre TF spielt vor allem bei der Pathogenese der Sepsis und der damit assoziierten Disseminierten Intravasalen Gerinnung (DIC) eine wichtige Rolle. In der vorliegenden Arbeit zeigte sich, dass TF bereits nach einer fünf minütigen Stimulation von Vollblut mit fibrillärem Kollagen in Monozyten-Plättchen-Komplexen und Neutrophilen-Plättchen-Komplexen gemessen wurde. Die TF Präsentation in den Leukozyten-Plättchen-Komplexen war streng abhängig von der vorhandenen Plättchenzahl. Mit Hilfe von Vollblutgerinnungsmodellen und prokoagulatorischen Assays konnte gezeigt werden, dass der schnell präsentierte Tissue Factor funktionell aktiv war und somit die Fibrinbildung auslöste. Elektronenmikroskopische Aufnahmen zeigten, dass das TF Antigen auf der Oberfläche von Plättchen vorhanden war, die sich in Konjugaten mit Leukozyten befanden. Um die Frage nach dem Ursprung dieses intravaskulären TF zu klären, wurden Monozyten, Neutrophile Granulozyten und Plättchen auf ihren Gehalt an TF Protein mit einem Double-Sandwich-ELISA untersucht. Dabei konnte nur in den Plättchen TF Antigen nachgewiesen werden. Weitergehende Untersuchungen zeigten, dass TF in der Tat in den a-Granula und dem „open cannanicular system“ der Plättchen lokalisiert ist. In den Plättchen und in deren Vorläuferzellen war keine m-RNA für TF vorhanden. So bleibt die letztendliche Quelle des intravaskulären TF bis auf weiteres ungeklärt. Durch Hemmung von Adhäsionsproteinen, die die Interaktion von Plättchen mit Leukozyten vermitteln, wie P-Selektin und CD40L, konnte die TF-Präsentation in den Plättchen-Leukozyten-Komplexen inhibiert werden. Daher ist davon auszugehen, dass mehrere Adhäsionsproteine an dem Prozess der Präsentation von intravaskulärem TF beteiligt sind. Ein aus den Ergebnissen der vorliegenden Arbeit abgeleitetes Modell der Aktivierung des intravaskulären TF geht davon aus, dass in dem zwischen Leukozyten und Plättchen entstandenen Microenvironment ein von dem Plasma weitgehend unabhängiger Raum entsteht. In diesem Microenvironment wird möglicherweise der von den aktivierten Plättchen sezernierte TFPI durch die leukozytenassoziierte Elastase sowie weitere Proteasen und reaktive Sauerstoffspezies inaktiviert. TF kann damit zusammen mit FVIIa und FXa die Gerinnung starten. Die Ergebnisse lassen vermuten, dass die gesamte Blutgerinnung auf der Oberfläche von Plättchen stattfinden kann. Der intravaskuläre TF spielt vermutlicherweise eine Rolle bei der Aufrechterhaltung der Gerinnung innerhalb des lumenwärts wachsenden Thrombus. Somit kann die Fibrinbildung gezielt dort aktiviert werden, wo sie benötigt wird, um den Thrombus zu stabilisieren. Das Vorhandensein eines schnell aktivierbaren, intra-vaskulären Tissue Factor Systems stellt ein neues Konzept dar, um sowohl den physiologischen als auch den pathologischen Gerinnungsstart besser zu verstehen.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 01/19
Plasminogen wird durch verschiedene Proteasen proteolytisch gespalten. Zu den Enzymen, von denen bekannt ist, daß sie Plasminogen an definierten Peptidbindungen prozessieren können, gehören Elastase aus polymorphnukleären Neutrophilen (PMN) und Metallo-Elastase aus Makrophagen. Ein Spaltprodukt ist Miniplasminogen, das die proteolytische Domäne und den Kringel 5 umfaßt. Die Spaltstelle bei Val441 ist charakterisiert und ein Sandwich-ELISA gegen die Neodeterminante ist etabliert. Das dabei entstehende Counterpart besteht aus den Kringeln1-4. Es wird Angiostatin genannt, weil es hemmend auf die Neubildung von Gefäßen wirkt. Im Rahmen dieser Arbeit sollte untersucht werden, ob Miniplasminogen unter pathologischen Bedingungen wie Sepsis, Peritonitis und Tumorerkrankungen auftritt, um daraus einerseits den Einfluß der Elastase abzuleiten und Einblicke in die pathophysiologischen Abläufe bei Entzündung und Tu-morgeschehen unter Betrachtung der Plasminogenspaltprodukte in Korre-lation zu anderen Parametern zu gewinnen. In Vorversuchen konnte gezeigt werden, daß unter dem Einfluß von aktivierten polymorph-nukleären Neutrophilen Miniplasminogen aus Plas-minogen generiert wird. Von den potentiell an der Proteolyse beteiligten En-zymen konnte in vitro nur bei dem Einsatz von PMN-Elastase Mini-plasminogen nachgewiesen werden, nicht jedoch von MMP-2, -8 und -9. In Untersuchungen zur Stabilität von Miniplasminogen unter verschiedenen Blutabnahmebedingungen waren Citrat-Proben den anderen Systemen (EDTAPlasma, Serum) überlegen. In Proben von gesunden Probanden konnte in keinem Fall Miniplasminogen über der Nachweisgrenze des ELISAs gemessen werden.Es wurden Proben aus klinischen Studien zu Sepsis, Peritonitis und Mammakarzinom ausgewählt, die auf Grund einer hohen PMN-Elastase-Konzentration ein Entstehen von Miniplasminogen erwarten lassen konnten. Ein Ausscheiden von Miniplasminogen über die Niere konnte durch Messungen im Urin ausgeschlossen werden. In Citratplasma-Proben von Peritonitispatienten war kein Miniplasminogen nachweisbar, in Peritonitisexsudaten desselben Patientenkollektivs waren Miniplasminogenwerte bis 90 ng/ml meßbar. Es zeigte sich allerdings keine Korrelation zu anderen Parametern (Elastase-Konzentration, Plasminogenkonzentration). Signifikante Unterschiede der Miniplasminogenkonzentrationen konnten zwischen den Mittelwerten der Proben der Patientengruppe, bei der therapeutisch Fresh-Frozen-Plasma intraabdominell appliziert wurde, und der Kontrollgruppe, sowie zwischen den Gruppen mit und ohne Tumorerkrankung nachgewiesen werden. Bei der Evaluierung von Serumproben aus einem Mammakarzinom-Kollektiv wurden Werte bis 52 ng/ml gemessen. Eine Korrelation mit anderen Parametern oder signifikante Unterschiede in den verschiedenen Subgruppen konnten auch hier nicht gezeigt werden. Ein Zusammenhang zwischen der proteolytischen Kapazität in den Exsudaten und der MPlg-Entstehung ließ sich nicht zweifelsfrei beweisen. MPlg ist daher – im Gegensatz zu dem Elastase-spezifischen Spaltprodukt des Fibrinogens (FEP) (Gippner-Steppert, 1991) - als ein spezifisches Spaltprodukt des Plg nicht für den indirekten Nachweis der proteolytischen Aktivität der PMNElastase geeignet. Erfolgversprechend könnten ggf. immunhistochemische Untersuchungen von Tumormaterial in Hinblick auf das lokale Entstehen von Miniplasminogen sein.
Die Diskussion am Ende des Artikels wurde gelöscht (§137l UrhG).
Wed, 1 Jan 1992 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9842/1/9842.pdf Fritz, Hans; Jochum, Marianne; Riel, K. A.
Wed, 1 Jan 1992 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9810/1/9810.pdf Fritz, Hans; Bernett, P.; Jochum, Marianne; Riel, K. A. ddc:610
In 38 traumatic knee joint effusions the proteolytic enzyme PMN-elastase (PMN-E) and the repair marker procollagen III aminoterminal peptide (PIIINP) were determined. According to the period between trauma and first aspiration of the effusion, the patients were divided into 3 groups. Group I (17 patients; period between trauma and first aspiration not longer than 72 hours) showed high concentrations of PMN-E (up to 5400 ng/ml) and low concentrations of PIIINP (
Mon, 1 Jan 1990 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9758/1/9758.pdf Fritz, Hans; Fink, Edwin; Schomburg, Dietmar; Vasel, Birger; Hecht, Hans-Jürgen; Frank, Ronald; Blöcker, Helmut; Maywald, Friedhelm; Szardenings, Michael; Collins, John
Hemodialysis treatment is associated with activation of neutrophil granulocytes. Pentoxifylline has been shown to inhibit neutrophil activation in vitro and in vivo. We investigated the effect of pentoxifylline on leukocyte and platelet counts and on plasma levels of extracellularly released neutrophil elastase and lactoferrin during a four-hour hemodialysis treatment. Eight patients received 400 mg of pentoxifylline or placebo orally twice a day over 14 days and an additional dose of 400 mg of pentoxifylline intravenously during hemodialysis. Each subject served as his own control in a randomized, double-blind, cross-over study. Combined oral and intravenous treatment with pentoxifylline prevented neither leukopenia nor neutrophil degranulation during the time interval studied. Elastase plasma levels paralleled the drop in leucocyte counts and thereafter increased similarly in both groups. Lactoferrin plasma levels exhibited less increase in the treated group; however, this effect was not statistically significant. This may be due to the small number of cases studied and to difficulties in reaching effective plasma levels without side effects.
Mon, 1 Jan 1990 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9784/1/9784.pdf Fritz, Hans; Jochum, Marianne ddc:610, Medizin
Mon, 1 Jan 1990 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9772/1/relationship_between_angiotensinogen_alpha-1-protease_inhibitor_9772.pdf Jochum, Marianne; Kienapfel, G.; Kellermann, W.; Hilgenfeldt, U.
Fri, 1 Jan 1988 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9332/1/9332.pdf Jochum, Marianne; Inthorn, D.
Fri, 1 Jan 1988 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9340/1/9340.pdf Redl, H.; Fritz, Hans; Jochum, Marianne; Lang, H. ddc:610, Medizin
Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9304/1/9304.pdf Jochum, Marianne; Thetter, O.; Siebeck, Matthias; Welter, H. F.
Wed, 1 Jan 1986 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9488/1/9488.pdf Schill, W.-B.; Pabst, W.; Jochum, Marianne
Wed, 1 Jan 1986 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9486/1/9486.pdf Fritz, Hans; Jochum, Marianne; Dittmer, H.
Wed, 1 Jan 1986 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9298/1/9298.pdf Fritz, Hans; Siebeck, Matthias; Welter, H. F.; Jochum, Marianne
Tue, 1 Jan 1985 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9478/1/9478.pdf Bieth, J. G.; Pauli, G.; Boudier, C.; Pelletier, A.; Jochum, Marianne
Tue, 1 Jan 1985 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9292/1/9292.pdf Heidland, August; Neumann, S.; Jochum, Marianne; Hörl, W. H.
Tue, 1 Jan 1985 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9476/1/9476.pdf Fritz, Hans; Thetter, O.; Siebeck, Matthias; Wiesinger, H.; Jochum, Marianne
Tue, 1 Jan 1985 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9291/1/9291.pdf Fritz, Hans; Dittmer, H.; Duswald, Karl-Heimo; Jochum, Marianne ddc:610, Medizin
Tue, 1 Jan 1985 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9479/1/9479.pdf Fritz, Hans; Schramm, Wolfgang; Jochum, Marianne; Duswald, Karl-Heimo ddc:610, Medizin
Kommentare auf Seiten 726-727 gelöscht (§137l UrhG).
Tue, 1 Jan 1985 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9232/1/9232.pdf Fritz, Hans; Jochum, Marianne
Tue, 1 Jan 1985 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9482/1/9482.pdf Jochum, Marianne; Junk, A.; Geiger, Reinhard ddc:610, Medizin
Sun, 1 Jan 1984 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9223/1/9223.pdf Neumann, S.; Dittmer, H.; Duswald, Karl-Heimo; Jochum, Marianne
Sun, 1 Jan 1984 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9219/1/9219.pdf Fritz, Hans; Dittmer, H.; Duswald, Karl-Heimo; Jochum, Marianne
Sun, 1 Jan 1984 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9220/1/9220.pdf Jochum, Marianne; Neumann, S. ddc:610, Medizin
Sun, 1 Jan 1984 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9224/1/9224.pdf Hofstetter, A.; Schill, W.-B.; Friesen, A.; Jochum, Marianne; Schießler, Hans ddc
Sun, 1 Jan 1984 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9229/1/9229.pdf Pepys, M. B.; Mallaya, R. K.; Jochum, Marianne; Christen, P.; Schnebli, H. P.
Sun, 1 Jan 1984 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9450/1/9450.pdf Fritz, Hans; Dittmer, H.; Duswald, Karl-Heimo; Jochum, Marianne
Sun, 1 Jan 1984 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9475/1/9475.pdf Jochum, Marianne; Hiller, E.
Sat, 1 Jan 1983 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9448/1/9448.pdf Schweiberer, Leonhard; Fritz, A.; Jochum, Marianne; Duswald, Karl-Heimo
Sat, 1 Jan 1983 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9216/1/9216.pdf Fritz, Hans; Hiller, E.; Duswald, Karl-Heimo; Jochum, Marianne
Sat, 1 Jan 1983 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9214/1/9214.pdf Hiller, E.; Duswald, Karl-Heimo; Fritz, Hans; Jochum, Marianne
Sat, 1 Jan 1983 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9213/1/9213.pdf Duswald, Karl-Heimo; Jochum, Marianne; Schnebli, H. P.; Nelles, L. P.
Sat, 1 Jan 1983 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9212/1/9212.pdf Fritz, Hans; Witte, J.; Duswald, Karl-Heimo; Jochum, Marianne ddc:610, Medizin
Thu, 1 Jan 1981 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9441/1/9441.pdf Fritz, Hans; Heimburger, N.; Lander, St.; Jochum, Marianne ddc:610, Med