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Good afternoon, my name is Steve Dale, I am on the board of directors of the Winn Feline Foundation which is something I am so proud to say I am because I think I have something in common with everyone in the room that would be I kind of like cats. Does anyone have a cat?
You know I am tired of cats getting kind of the short shift. Here is what I am talking about, more cats are given up to shelters than dogs are. Fewer cats are identified, we tend not to microchip cats or put IDs on them, you know collars with a tag saying who they are. Fewer people actually go to a shelter to look for that lost cat than a dog, which is shocking. When they do they are not as likely to find the cat that is their cat. More cats are just let outside. We tend not to do that with dogs. I mean let outside, close the door and we do not want them back. Not any of us in this room, I am talking about just people in general. Cats do not see the veterinarian as often as dogs, about half as often as dogs. Yet we have more cats in America than dogs so at some level cats are man’s best friend and I am just kind of tired of cats being the Rodney Dangerfield of pets. We need to change all that and give cats the respect they deserve.
That is part of the reason that for 383 years the Winn Feline Foundation has been holding a symposium. Of course I said that in cat years but we have been doing this for a very long time. I will talk a little about the history of all of that in just a little bit. How many of you have been to one of our symposiums before? Oh my gosh, everybody in the room. For those who did not raise their hands, welcome! This is a good thing, it is a great learning opportunity. Some number of years ago we though what a great opportunity to get CE credits for veterinary professionals; there are veterinarians in the room, veterinary technicians, a special welcome to all of you. Homeagainheroes.com (I think it is .com) are having a contest where you can nominate a hero, anybody who in any way is a hero for cats or dogs, it doesn't much matter, for companion animals. It can be a first responder. It can be a shelter volunteer. It can be anyone. Well for those veterinarians in the room you are heroes in my world because you save animals all the time.
This is kind of like the 411 on what the Winn Feline Foundation has been doing since 1968. It was developed originally as an idea from the Cat Fanciers Association. So Cat Fanciers Association people, thank you! You made it possible for us to save lives and that is what those of us who are involved in the Winn Feline Foundation, that is all we want to do. We want to make a difference for cats. I like dogs, I have two myself at home. A lot of you have dogs, right? Nothing wrong with dogs but let me tell you a little secret. The Canine Health Foundation, they raise millions and millions of dollars. They do, and for every (I am making up this number but is not too far from the truth) million dollars they raise we struggle at the Winn Feline Foundation, the only organization on the planet that solely raises money for felines; we struggle to raise $300. It is easier for whatever reason to raise money on the dog side. That has to be changed because cats get sick too. We have made a difference for all of those who kind of raised their hand when I said do any of you have a cat? Of course you kind of raise your hand in this group, right. Lots of cats over the years, probably breed cats for most of you in this room. This is a small partial list. I could do a whole hour on just what the Winn Feline Foundation has done in all of the years the Winn Feline Foundation has been there. Sometimes what we do is the seed work.
We do the work and then another organization, well for example with feline leukemia. No one knew really what the feline leukemia virus was or what it did or how it worked. It was called this like, rinky lymph node disease. No one even had a name for it. It was with the Winn Foundation seed money that researchers and investigators were able to figure out in what in fact feline leukemia is and how cats got it and it was Morris Animal Foundation that then came in once that knowledge was learned and said okay now we can create a vaccine. We often work in tandem in a sense with other organizations but there is not a cat that any of you have, and I would sat there is not a cat in America that in some way, probably in lots of ways, definitely in lots of ways has not been changed or impacted by the Winn Feline Foundation. Do any of your cats eat? Even the very food that we feed our cats, unless you make it yourself and even then what we know should go in that food, that has been studied by research that long ago, before my time, that the Winn Feline Foundation funded. I am glad you are here. A part of our mission is that funding, but a part of our mission also is education.
You know what I need, oh this is so embarrassing. Yes, thank you. By the way, the board members or many of the board members of the Winn Feline Foundation are here. That is Vicki Thayer, president of the board of directors. Dr. Thayer, stand up please!
The other board members of the Winn Foundation, my colleagues on the board, please stand up! Come on!
It is truly a wonderful board; we all work for the same thing. Every year that I have been at this podium, I have been lucky enough to be able to acknowledge my colleagues on the board. What I have never been able to do until now, this very second is acknowledge maybe the most important person in the room! For the people that are not in this room they can later watch this because we have a videographer, Dr. Thayer’s husband Bob is right over there!
You know there are not many cats and we are going to learn in a second whether it is true or not what I say as Dr. Quimby will verify this or not. Maybe there are not any cats that are lucky enough to live beyond the age 8, 9 or 10 that do not have some sort of renal insufficiency. We thought this is an important topic to talk about because it affects so many different cats. The Winn Foundation is working very hard to help researchers learn more about this. Following her graduation from the University of Wisconsin, Madison School of Veterinary Medicine, Dr. Quimby completed a small animal rotating internship in Sacramento. She then pursued her interest in feline medicine in private practice at a feline exclusive clinic in Grand Rapids, Michigan. Wanting to learn more about medicine and the advance in the state of medicine for cats in particular, Dr. Quimby completed a small animal internal medicine residency at Colorado State University where she continued to concentrate on feline medicine. During her residency she specialized in feline kidney disease (no surprise) and also respiratory disease. She recently completed her PhD exploring several aspects of feline kidney disease including palliative stem cell therapy and renal aging and is now a faculty member at Colorado State University. Please help me welcome Dr. Jessica Quimby.
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Beginning of Dr. Quimby's Audio.
Dr. Jessica Quimby:
Thank you very much. It is an honor to be invited to speak here at the Winn Symposium. I am just going to take a moment to pull up my presentation.
What I would like to do this evening is talk a little but about some of the research that we have been doing at Colorado State University. As mentioned with that fabulous introduction what I have been focusing on in my life is basically the study of chronic kidney disease in cats. This is something that I have always been very passionate about and there is so much work to be done in this area, I will probably be doing it for the rest of my life. This is what we have done so far with the help of the Winn Feline Foundation and I wanted to talk a little bit about two of our big programs of study that we have going on at this point in time. With that like you mentioned, it is a very, very common disease in elderly cats. When we think about the number of cats that we have in the US, it is estimated to be approximately 24 million cats that probably suffer from this disease. We have literature that tells us that about 30% of elderly cats are affected by chronic kidney disease and honestly I do not believe those numbers. When we see what the cats that come to us at Colorado State and when we talk to practitioners, it is actually hard to find an elderly cat that is not affected to some degree by this disease so as we are taking better care of cats with better medicine they live longer and they tend to get chronic kidney disease if they are not affected by something else first. This has really become a major management issue for us. Unfortunately we do not know why it is that they are getting chronic kidney disease. Why is it so common in elderly cats and why is it that we cannot do anything for them? We need to find out what is causing this disease and also what we can do.
As many of you know, there is not anything that can be done about the disease other than a kidney transplant. It really becomes incumbent upon us to find additional treatment modalities that we could use. What can we understand about this disease so that we have a better way to treat them? That is really some of what my research has been doing is to look for additional options for these animals.
There are two projects I would like to talk about as you know. We will talk about the stem cell program and then we will talk about supportive care with appetite stimulants as they get this disease. The stem cell program is I guess our hottest topic. It is something that people always ask me about, what do we know about this disease and why do we think that stem cells potentially can treat this disease?
So just a little bit about why, where did this idea come from? We were sitting around one day, you know, contemplating kidney disease as happens a lot at CSU and thinking to ourselves, what can we do? What is in the literature that would be novel that we could apply to this disease process? There is actually a huge body of literature about stem cells and acute kidney injury and chronic kidney disease. There are literally hundreds, at this point in time, of different studies in rodents that tell us that stem cells could be beneficial for the treatment of chronic kidney disease. When you read some of these articles they are really compelling. Animals with acute kidney injury get stem cells and they live and the other animals do not, it is that simple. Animals with chronic kidney disease have an improvement in their numbers. Their creatinine improves. They have decreased proteinuria, if that is present, and they have decreased inflammation within the kidney and also decreased scouring or fibrosis within the kidney. This is all in rodent models. The question is, can we apply that to our cats and help them out with their disease process. Then the question is well how would stem cells be helping out the chronic kidney disease or the acute kidney injury process? A lot of people always ask me, is it – are we making new kidneys? Well unfortunately we are not making new kidneys. It is actually an effect most researchers now believe is what we call paracrine effect. So there is cellular messaging that is happening within the kidney. There is all this inflammation and scaring that is happening in the kidney as the disease progresses and there are little messengers that are telling the kidneys ‘Okay you just need to stop being inflamed, you need to repair’ and the stem cells are very helpful for that process. That is really what they are doing and we call that the paracrine effect of the stem cells. They are anti-inflammatory and they also protect vasculature. So when your kidney is diseased the vasculature, those little blood vessels become divorced from the cells that they are supposed to feed and that is part of the process. The stem cells are thought to help with that and that is part of what we really think their goal is or the effect that they would be having in the kidney.
We read all of this literature and we say wow this is fascinating, how can we apply this to our cats?
Why, and I think a picture is worth a thousand words and I want to show you these images so you would have an idea of what we would hope the stem cells would be doing. This is what we see when we look at interstitial inflammation in the cat kidney. On the left we have a normal cat and there are all the beautiful little tubules and you do not see a lot of purple in this picture. On the right this is chronic kidney disease and all of the purple cells that you see are inflammatory infiltrate coming in to the kidney and destroying the architecture in there. That inflammation is then later replaced by scaring once the normal architecture has been destroyed. We see this as they progress through their disease. We have been looking at the histopathology. We have been looking at these kidneys throughout the stages of chronic kidney disease. In this picture blue is fibrosis or scaring. This is what happens as cats go through the stages of their kidney disease. They start out and there is only a little bit of blue. Then as they progress more and more inflammation and more and more scaring occur until the kidney is pretty much replaced with tissue that does not function. Our goal is to really slow down that progress and that is what we are after with this particular treatment.
With that in mind after having read these articles it was honestly really my idea to start stem cell research at Colorado State to study chronic kidney disease. That was the whole point of our program as we read these articles and we were really, really interested in this, but no one had done this. So we had to start somewhere learning about feline stem cells, learning where do we get feline stem cells from, how do we grow them. We were the first feline stem cell program in the country and honestly we could not have done this without the Winn Foundation because when you ask for money for this type of thing people say ‘You want to do what with stem cells?’ So it becomes a little bit of a problem to start a program from the ground up with something that is really innovative and we were lucky enough to get support for that project and this has started off our entire program for stem cells at CSU.
We wanted to learn more about feline stem cells in general and we also want to basically, we have worked through our series of pilot studies looking at what could these stem cells do for cats with chronic kidney disease.
I am going to talk about three different series of pilot studies that we have gone through looking at putting the stem cells directly into the kidney. We want to find a way to easily give them to cats so we have worked on cryopreserving them or freezing them so we can just thaw them and give them to the cats. Also, cryopreserving the fat so we can then thaw the fat and make stem cells and give them to the cat. I will explain a little bit more about that shortly.
I do also want to mention that one of our other visions of the program was to look at stem cells for the treatment of asthma and IBD and I am really proud to say that we now have collaborations with two other researchers who are also Winn funded that are looking at stem cells in asthma and IBD.
Where do we get the stem cells? This is always the question. These are adult stem cells so this does not involve embryos. I once had a women ask me, are you grinding up kittens, Dr. Quimby? I said no, we are not grinding up any kittens, I swear! A lot of this work originally started in horses in veterinary medicine and horses are very large and it is very easy to get bone marrow from them. They get it from the sternum. It is not fun, for the veterinarians in the room, to bone marrow a cat. So this is where all the body of knowledge was and we started off doing bone marrow derived stem cells. Not fun but then adipose has gained in popularity. Obviously this is something that we have a lot of! Not an issue to get adipose tissue. We also have several other companies that are now looking at shall we say spare bits that you can get stem cells from. I believe one of the other universities is going to be looking at, once you spay and neuter a cat can you use the spare bits for stem cells for that animal later. That would be another source. For us we have decided upon adipose. One of the reasons for that is in our original studies we actually compared; when I was getting that bone marrow, in the elderly cats it is very hard to grow the bone marrow. It is very hard to obtain the bone marrow and I thought this is just not practical. We need something easier. We have some really healthy spoiled and a little bit plump research cats and they would provide the fat for a lot of our studies and I will talk about that. The other thing we discovered was the adipose grows way more stem cells than the bone marrow does. So, you can get a little bit of bone marrow or a little bit of adipose and it grows many, many more stem cells much quicker. That is what this graft actually shows. In the red you get a much higher yield from the adipose and it is easier. So for cats adipose is the way to go. And who needs the little paunch, so we focus on the paunch and we give our research cats a little tummy tuck before they get adopted and they give us stem cells. That is where they are coming from.
The next big question we get is, ‘Are they stem cells?’ Well how do we know it is a stem cell? This is a question that is something that understanding the product that you are using is really important especially when we have a lot of companies who are providing stem cells for use in clinics. I want to explain a little bit about how we know it is a stem cell.
First of all it seems almost like science fiction to me honestly to this day. You take some fat, you grind it up and you put it in a flask and several days later stem cells stick to the plastic and you start growing stem cells in culture. It is an amazing thing to see and you get this beautiful little arrangement of cells that stick to the plastic. For whatever reason they like to stick to plastic and we use this to our advantage to isolate them in culture. There are also different ways that we can characterize them with little surface markers using flow cytometry on the surface of the cell. Those markers are not specific to stem cells so we do not find them to be very useful. We do it for the sake of the science of saying okay we characterized our stem cells and we know they are positive and negative for what they should be but it is not nearly as entertaining as the other thing that they can do which is to differentiate into different cell types. If you want to say ‘I have stem cells’ you need to be able to show that your cells can actually be turned in cells of other different lines. Again this is a thing that really is fascinating to me.
In the lab we take our typical stem cells and we can then make them by adding certain substances to their media turn into cells that produce fat, calcium or bony constituents or little tiny cartilage globules so literally you have got these stem cells and they will start making little blobs of cartilage right in the flask. Then you can collect this material and test it to say look we have cartilage that is being produced by these stem cells.
For them to be able to do this, this is called trilineage differentiation, that tells you that you have a stem cell that could be all these different cell lines and then you can prove the cells. With the cells I am working with that is what we are talking about, they can do all these different things. They jump through their little hoops and now we know who they are.
I do want to make sure that stromal vascular fraction is basically, that people understand what that is. When you process the fat and you spin it down you have what we call stromal vascular fraction. This does have stem cells in it but this is often the product that has been use commercially as a stem cell product. So if you harvest fat and you send it away to a company and it comes back to you 48 hours later, you have stromal vascular fraction. You do not have isolated stem cells. That takes 7 to 10 days in culture, right. It takes a couple of weeks to grow them up. There are stem cells in that population but there are also other cells, other than stem cells and interestingly enough we just do not know enough about this particular substance. There have been studies that have shown that it too can be helpful for disease. We are not saying that this product is not a stem cell product, it is just different. It is important for people to understand that there are different types of stem cell products out there and I hear everything being called stem cells and that can be a little frustrating for us because there is a difference there.
What were the goals of our studies. We wanted to create a feline friendly treatment and what I mean by that is it has to be not some big convoluted thing that is hard on the cat that involves multiple procedures. I really want something that is going to be clinically applicable. That is what we do is come up with something that will actually work in real-life practice. I was in practice, I know what it is like and it has to be reasonable if it is going to be a treatment that is actually going to work in terms of logistics and it also has to be effective. Those are the two biggies, it has to be logistically possible and also efficacious and that is really what we are going for. Our hypothesis is of course we do not want to hurt or kitties, we want to make them better and we also want something that is easy to give and it helps out with their chronic kidney disease which is really kind of a tall order.
I am going to describe the series of pilot studies that we have gone through looking at different ways that we can give stem cells and the potential effects of it on the cats and their kidney disease. When this first started to come out, everybody thought, there was a big argument in the literature about can you just give the stem cells willy-nilly to the cats and will they find the kidneys or do you have to put the stem cells in the kidneys. Because we were unsure in the literature and the experts in stem cells were a little but unsure at that time we chose to do our first pilot study by putting the stem cells directly in the kidney. Also because of the current literature at the time we elected to get the stem cells from the cat with chronic kidney disease. This is autologous stem cell therapy. We would take the bone marrow or the fat biopsy from the cat with chronic kidney disease. We would grow those samples up in the lab which of course takes two weeks and then give it back to that patient. We did both bone marrow and adipose derived and when you do a procedure on your elderly little patient there is a lot of praying involved in making sure that those cells grow. So that was stressful. I thought well maybe this is not the best way to do this. We will look at other things in the future. Then we would give those cells back into the kidney with ultrasound guided injection. We dose escalated in this study. All of the cats actually did really well and you would think that this is a little bit more of an invasive procedure but if it were to work this would be great. What we really saw in this study was the cats had mild improvement in their numbers and we looked at their GFR or there glomerular filtration rate (excuse me) and some cats really had a significant improvement on an individual level in their GFR but it just was not enough for me to say it is worthwhile to go through this whole procedure of collecting their bone marrow, their adipose and injecting into their kidney. The disadvantages really kind of seemed to outweigh the benefits and when we quizzed the owners who were involved in this first study, they said ‘Yea, you know it could be easier.’ What could we do to improve the feline friendly part of this whole thing?
Basically there were too many procedures. We were doing GFRs for the sake of science, you would not do that in practice but we needed to determine whether it worked or not. Then it is hard for these elderly kitties to go through that procedure of collecting the fat. They have to be sedated in order for the ultrasound to happen to put in into the kidney. So what if we could just give it IV? Actually another paper came out at that time that said giving it IV to the rodents was very, very helpful. We decided to change our program and go in that direction. In addition the elderly kitties posed a problem, it is not fun to bone marrow an elderly kitty and also the cells just do not grow as well as I showed you.
This is Frankie and Frankie is actually the kitty who was in our first pilot study that started Frankie’s fund for feline stem cell research, her mom did actually, not the cat of course. Frankie was a little bit plump when she was first diagnosed with kidney disease so we decided to try the adipose route at that point in time and her cells grew fabulously. We compared the two in those cats and that is when we decided to transition to the adipose. It was much less nerve wracking if you will to make sure that you were able to get a treatment for the patient. The other thing though would be, I thought to myself, why are we trying to get these stem cells from the elderly patient. Wouldn’t it be better if we had fat donors? This is where our plump little research kitties come in. It would be much easier if we could use allogeneic therapy and have cells just waiting there for them to use and then the elderly kitty then would not have to go through that procedure and then you could treat acute kidney injury or lily toxicity or some other thing where we did not have time to wait for the cells to grow. So, that has been another big focus of our program is trying to arrange that. So we actually switched to allogeneic stem cells at that point in time and that is where all of our research kitties like I said get a little tummy tuck and they do very well with that. It is pretty noninvasive for them.
This is the initial pilot study that we had five kitties that were involved in this particular study. Again we now were going IV and the protocol, this is our new study. We switched to a repeated IV administration of stem cells. Now that it is easy we can easily give it in a repeated manner and see how they do with repeated injections. So they would get stem cells once every two weeks and then the other big question everybody asks us is well how long does it last if we give stem cells, is that going to last six months? Will it change things and help for a year? Then we actually gave them once monthly injections after that to see if any effect we saw would last from that. Realistically again from a logistical standpoint giving them an injection IV every two weeks is not logistically realistic. We also did clinical monitoring in these kitties and the other big thing I want to say is how do you know what is going on in the kidney? So because we cannot do a kidney biopsy, it is not safe, we have actually developed a program looking at cytokines or mediators of inflammation in the urine and we used this as a proxy to determine if we are affecting things in the kidney. Can we make that inflammation in the kidney better? So that is the other thing we are measuring. All of this is pretty much true for the pilot studies that I will talk about with little amendments.
This is Colby, he was our poster child for the IV study and he was owned by one of the gals in the VTH. We actually saw a significant decrease in creatinine in this first study and we were very excited about this. It was a relatively small decrease but all of the cats had it and that was kind of a really exciting point for us. We elected to go on at this point in time. All of the cats did very, very well. None of them had any problems so this is where the people start to say well you are giving someone else’s stem cells to these cats. How are they not having a reaction? Stem cells are actually immunoprivileged and you can give some cat stem cells to cat B and not have a problem because the immune system does not see those stem cells. None of the cats had any problems and actually in some of the papers they give different species of stem cells to rodents. So they will take human stem cells and they will give rodents human stem cells and there is no reaction. That is how immunoprivileged they are. We did see that small but significant decrease in creatinine and also in urinary cytokines and so this as a first IV pilot study was exciting but then with the creatinine you really cannot tell because if the cats change weight their creatinine might also change so we needed a little bit more definitive measure of kidney function. Then unfortunately the effect seemed to wane over time so once we went to the monthly injections their creatinine kind of popped back up again so we though ‘Oh well, maybe it does not last as long as we would like it to.’ All of the kitties in all of the studies, I should mention we are following until the time of euthanasia so in the end we will be able to look back and see who was in studies and did they live longer than average that we would expect for chronic kidney disease patients.
Then we decided to move on to pilot two and we added in an iohexol clearance test which is another measure of GFR that can be done easily within clinic and we increased the stem cell dose because there was some indication that a higher dose might be better. This is Truman, she was one of our research kitties that got a tummy tuck and got adopted.
Pilot two was five kitties and in this particular study we actually did not see a significant change in the creatinine or in the urinary cytokines so it kind of give you an idea they were straight across the board. Their urinary cytokines did not change over the course of the study either but we ran into another issue. I am sorry, this first. The one thing that always gives us hope is no matter what pilot study I am in there are always some cats that do fabulously. Even when their creatinine does not change, the owners invariably report, they are like a kitten again! They are leaping around the house and doing really well. When we look at the GFRs, the three dotted lines are cats that did not get stem cells, they were the controls. We have cats, like cat 1 who had a 75% increase in their GFR. That is huge if you actually have hardly any kidney function to start with. As a general rule the control cats never vary more than 10% so every once in a while in these studies we have a cat with a GFR that really improves as a result of the stem cell therapy even if their creatinine does not seem to change. I honestly do not have a great explanation for that other than it is what continues to drive us forward.
Variable responses in their GFR, however these were the cryopreserved cells and when we increased the dose we started having problems with giving the cells. Some of the kitties would get increased respiratory rate and others would have nausea and vomiting as I was giving the cells. It actually turned out that this was a problem with cryopreservation, not the stem cells themselves because we then subsequently gave fresh; we have never had any problems with fresh cultured cells. But, kitties like to vomit. They will vomit when you give them substances and so something about cryopreserving the cells and then giving it to the cats be it the cryopreservation, I mean we washed them afterward, we were very, very careful to wash out the freezing media and everything. The cats still would react to these cryopreserved cells so some more grey hairs were created during this pilot study and we decided that we needed to change things because again, rule number one, do no harm. We need to be effective but we needed to not harm kitties. Then in a moment of one of those serendipitous scientific moments, I got really sick of processing fat one day and I just threw it in the freezer. We had a lot of fat to process and we discovered that you can actually just freeze the fat and then thaw it out and grow the stem cells up fresh which is what we do now for all of our protocols so you have fresh cultured cells that you can use and the cats have absolutely no problem with them. It takes about 10 days to do that in the lab. We also in this pilot study three we added in nuclear scintigraphy. With scintigraphy when you are looking at GFR you can tell the difference between kidneys so you can actually take the GFR of each kidney to see, a lot of these kitties have big kidney, little kidney syndrome right, where one has been injured and the other has not and it has gotten bigger because it is trying to recover, a little hypertrophy. The question was do the stem cells help out the big kidney more? Do they help out the little kidney more? Or does it not make a difference so that would give us a little bit more information. We kept the dose the same because the question that we really wanted to answer with the pilot study was what is going on with those cryopreserved cells. If we give these fresh cultured cells and then the cats not have any problem that would answer that question for us.
Pilot study three again was five kitties and I should say that these pilot studies are so small because one of the caveats or one of the requirements of being in this study is that they have to be an elderly cat with only kidney disease. That is kind of a problem when it comes to enrolment. We screen a lot of cats and the reason we have to be so stringent about it is because the stem cells are attracted to everything so if you have IBD or if you have skin disease or you have some other condition your stem cells are going to be attracted to areas of inflammation or infection so nothing else can be going on if we are going to get a good idea of whether or not they can really help out with the kidneys. We screen a lot of kitties and that is why our pilot studies tend to be on the small side but it gives us a good idea of what is going on and each time we change a little something.
With pilot three again we did not have a clinically significant change in serum creatinine or the urinary cytokines but the same thing happened with the GFR. We had kitties that had a 63% increase in their GFR and a 91% increase in their GFR. The GFR in the one cat almost doubled what it had been before. Then we have one kitty that went down. Well this tells you how sensitive GFRs are to things because unfortunately Harley was constipated that day. He was having issues. Part of the stem cell study is that you cannot have any treatment changes and they have to be stable chronic kidney disease cats but that is almost like an impossible thing to be a stable chronic kidney disease cat. Throughout the course of the eight week study, this was a cat that had intermittent bouts of constipation unfortunately on the day that he came in he was constipated and there was also a snow storm so mom brought him up the CSU the night before and stayed in a hotel. Unbeknownst to me, I probably would have said, let’s just reschedule. So poor Harley was constipated, stayed in a hotel overnight and probably did not drink what he normally drinks. That has the power to change what his GFR is unfortunately. So clinically he had no change but those GFRs are really sensitive and that is unfortunately one of the limitations of this type of measurement. Again 91% increase in GFR so this is really interesting and this is why we keep moving forward with this.
Conclusions from that, effects are variable. Quite variable in terms of what they can do. We did not see administration side effects when we used those fresh cultured MSC and that is now the way that all of our pilot studies move forward. We freeze the fat and we grow the cells from the fat and everybody does fabulous at home. As a note, we also think that stem cells are good for arthritis so some days I think we are just treating arthritis and everybody is running around like kittens feeling fabulous because their arthritis has been treated so it could also be very good for that. One of the cats that did very well had bad lumbosacral arthritis and I really do believe that probably made a big difference for him. We have been wanting to do an arthritis study but it is very hard to assess in cats and although we have force plate technology at CSU the cats just slink no matter what when they are in the clinic so you really cannot assess how they are doing with their arthritis, as an aside.
Future directions for the stem cell program: We still have like an entire; I swear there is like a 10-year plan in terms of chronic kidney disease for the program at this point in time. We are currently in the middle of a placebo controlled clinical trial with those fresh cultured stem cells and the one thing that was noted was that as the amount of stem cells may matter, we are trying to enroll cats with a lower level of chronic kidney disease or earlier stages. Because if you remember in those pictures I showed you, once they get to the end stage, it is already scarred. It is already fibrosed and we cannot turn that process around. We need to prevent it from happening so we are enrolling more stage 2 kitties. Well I have some 7 and 8 kg, almost 15 to 20 pound stage 2 chronic kidney disease cats somehow and so when they are getting a flat dose of stem cells that does not have the same effect as an under 2 kg chronic kidney disease cat, so this new pilot study actually administers the stem cells by weight so that everyone is getting per mass the amount of stem cell they potentially would need.
Further areas of research we will be looking at is actually going back to giving the stem cells near the area of the kidney so in the retroperitoneal space. Again, that would be something to get them in the area of the kidney. Would that be less of a problem? It is much easier to do that injection than it would be to do the intrarenal injection that we did before.
Then we continue to strive to know more about feline stem cells. What is the best way to cryopreserve them? What else can we apply them to? How do they work and how can we help out cats and all of their inflammatory diseases because they like to react to everything. How can we help them out with stem cells and what is the potential for that? So that is really the focus for the future direction of the program at this point in time.
With that I would like to transition over to talking about mirtazapine which is really one of my favorite subjects as well as an appetite stimulant and anti-nausea therapy for cats with chronic kidney disease. As I said this is a topic near and dear to my heart as I am sure probably everybody in this room has had a cat with chronic kidney disease and we spend all of our young years as cat owners getting them to not be fat and then once they get one of these terminal illnesses we spend every single day trying to get them to eat and it can be really challenging so this is where we can really get some help and help some of these patients out. What is the importance of nutrition and why do we worry about it?
Obviously they need to eat to live, very basically. It is really, really important for immune function, healing and strength, keeping up their attitude and their liveliness at home and there are actually a number of studies that show that a poor body condition is linked to a poor prognosis and this is true in any species and especially with chronic kidney disease. So once you become very, very frail, even as a human, your chances of doing well with dialysis are much less and if you are a dog or a cat with chronic kidney disease you will lose body condition, you lose energy and if you have another uremic crisis and you end up in the hospital, you just do not do as well. You have lost that energy reserve to get you through crisises and it ends up being the end of the road for those animals. Really the biggest thing to me is quality of life. This is really what cat owners see and struggle with every day and I have people who literally sit in the exam room and cry about the fact that they just cannot get their cat to eat and that really is just so moving to me and if we can do something to help with that process it is really quite powerful. It is very, very stressful and there have been a couple of quality of life surveys for cats, not for kidney disease but for other diseases. That is one of the number one things that people say is that just getting the animal to eat is just such a stressful thing for them. In the end this is why they get euthanized. If they keep eating and they keep their body condition up they keep going and they do much better with their disease. That is really the goal, the underlying tenant of this work is to help them out with that.
Just a little bit about mirtazapine and why we thought this would be a good idea to look into this further. It is actually an anti-depressant in people and strangely enough the major side effect is sedation which is not the case in cats. Often if owners have experience with this drug, they say eww that does not seem like a good idea and I say well cats are not people and it is different. We have different side effects. The major thing that we are interested in is this 5-HT3 receptor antagonist action. This is the same receptor as ondansetron and dolasetron or Anzemet so an anti-emetic and that is a really important point for this drug.
In humans and other species it has been shown to have the side effects of appetite stimulation and antinausea. If you are depressed and you are taking this drug and it makes you eat a lot, not really the best thing in the world right! So it did not turn out to be the best drug for depression because it just makes people eat and they get more depressed and it is a bad cycle. But, if you have cancer and you are depressed and you are nauseous it is a great drug and there have been a lot of studies that have shown that. The anti-nausea effects are actually quite fascinating so people who go under anesthesia and get really, really sick from anesthesia, some of you may have personal experience with that. There was a great study that showed taking mirtazapine before the anesthetic event greatly reduces the problems that people have with post anesthetic nausea. I thought that was a really interesting study.
Previous work that was out there that made us go hmm. There was a little open trial that was published and this has now gotten into VIN and everywhere else and this is the mantra that we are trying to fight against, 1/4 tablet every 72 hours. The thought behind that and this was extrapolated from human medicine. There was no data behind this recommendation whatsoever. Dr. Lunn and I gave this drug and we said this works fabulously. This is the best appetite stimulant I have ever seen but there is no way that 1/4 tablet every 72 hours is the correct dosing. We need more information. The reason why people thought this might be appropriate is because the way the drug is metabolized. It is glucuronidated in the liver and cats are very bad at that so it was thought, we need to give it less often because of this. Again there was really no information about pharmacokinetics in cats to say that this was the right dose so this was kind of the gauntlet or the glove thrown down for me. We need more information. This is a great drug but I really feel like we are using wrong. In addition to that my end goal was to use it for chronic kidney disease cats even though we use it for a lot of our patients at CSU. We know that renal disease delays its clearance by about 30% in humans and the question was, well if that is the case what is the effect in cats with chronic kidney disease and do we have to change the dose to make up for that?
The overall aim of the mirtazapine project was to investigate the use of mirtazapine as an appetite stimulant and we were aiming for chronic kidney cats. Because we knew nothing about the drug we had to start with normal cats and find out about how it worked in normal cats before we could get to the chronic kidney disease cats. Our hypothesis was that it would help these cats with the management of their disease. So we have gone through and over a series of about five years we went through a series of studies again. We did pharmacokinetic studies in young normal cats and this was a very clinical study so I basically took the doses that people were saying to give 1/8 and a 1/4 of a tablet which is 1.88 mg and 3.75 mg if you do the math and see what are we finding when we actually give those two tablets. This is a real life study and then we looked at daily dosing in young normal cats when we discovered that the pharmacokinetics was actually a lot shorter than anybody expected. Then we also decided that the high dose was a bit too much and I will talk about that in detail in a bit. We then tested it in normal geriatric cats and chronic kidney disease cats at that lower dose, that 1/8 of a tablet dose. We also because some people would say it is not an appetite stimulant, it does not work, you know I do not believe this. Then we actually had to show that it was an appetite stimulant. In young normal cats, we compared the placebo to the 1/8 of a tablet to the 1/4 of a tablet and basically recorded how much they would eat once they got that. Then last but not least that we have just about to be published is our chronic kidney disease clinical trial which is a placebo controlled blinded crossover study looking at the effect of this 1/8 tablet every other day dose for three weeks in our chronic kidney disease patients.
When we go back to the pharmacokinetics what did we learn from this. We did all three of those groups and this graph actually looks amazingly just like the graph in the human literature for humans. Basically what we saw is healthy cats are on the blue dotted line, the half-life was way shorter than anybody would have imagined. The half-life was 9 hours in cats and it is actually 30 to 45 hours in humans and it is administered daily. So right there that tells you that every 72 hours, there is no drug left by 72 hours. In 9 hours they have gone through half of it. The 72 hours part is pretty, not really what we were seeing but then if you are a geriatric cat in the green actually that does extend the half-life of the drug in your body. This is true in humans as well. As you get older your enzyme systems shift and so things change and often you metabolize drugs slower so in our older kitties we need to pay attention to that. Then having chronic kidney disease slows the processing of the drug even further so this is time to excretion right. As this goes up on the graph, that means it takes longer and longer for you to get this drug out of your body, so we discovered there was this nice movement as you add on disease processes from your healthy young normal cats to your chronic kidney disease cats and this is where our recommendation for the dosing came from. In healthy young cats it could actually be administered on a daily basis according to this information and so for cats that have no kidney or liver dysfunction, maybe they are boarding and they are not eating or they are having some other psychological breakdown; you could mirtazapine to keep them eating or if it is a pancreatitis cat this how we use this drug. Once we get a little bit older or we have chronic kidney disease then the half-life becomes more like 15 hours and the effect really does seem to last for up to every other day and I have some owners for whom the effect is so obvious some owners will give it every 36 hours instead of every 48 and they time it down to the minute.
In general people have been very happy with that dosing scheme.
What about the pharmacodynamics study, what about the actual dose? Which dose do we use and does it work. The pharmacodynamic study, many clinicians, student and people who work in the VTH brought in their kitties for the eating study. It was kind of like a little spa treatment really. Many of them enjoyed it very much. They had three separate one day stays in the clinic. They received in random order the placebo, the 1/8 tab or the 1/4 tab. Everybody was blinded, nobody knew what was going on and then we recorded hourly after they got this treatment how much food they ate. We would weigh it, how much they vocalized – meows per minute. Social interaction, were they hiding at the back of the cage, were they up at the front of the cage, you know rubbing, head butting and their activity in general. This was a pretty fun study I have to admit. Counting meows per minute was one of my favorite study parameters. Interestingly enough we actually saw that there was no difference in the effect between the low and the high doses. If you gave the 1/8 tablet or the 1/4 tablet they did not eat more if you gave 1/4 tablet but they ate a whole lot more than they did if they just had the placebo. In addition to that we had one cat that ate no matter what. He did not care and then we had one cat that shivered in the corner no matter what so they are cats right. They do not always cooperate but this is a very realistic representation of cats at large so we see no differences in the doses but we do see more side effects at the high dose and this was our clinical impression as well. Oh my goodness!
Sometimes we have owners who say mirtazapine is evil. I gave this drug and my cat is running around the house going meow, meow, meow, meow and yes one of my cats is the same way. I cannot give this medication in the evening and she even needs a lower dose. She gets 1/16 of a tablet and she is still a little bit on the edge. It is an individual cat thing. So if there is no difference in the efficacy we should really be starting with the lower dose particularly in our chronic kidney disease patients so we have less side effects but similar efficacy. That was really what that study gained us. In addition to saying for sure this drug is an appetite stimulant.
Last but not least we have the chronic kidney disease clinical trial. This was like I said a placebo controlled study so the owners did not know which the cats were getting and then it was crossed over so they would do one treatment and then the other. I asked them to just please be objective because once you give the mirtazapine it is clearly the mirtazapine because it works pretty well. There is this little thing at the beginning of the packet that says, ‘Okay we realize that once you start giving this drug you are probably going to know placebo versus not but carry on, please finish the study and please be as objective as possible.’ They got the 1/8 tablet dose every other day for three weeks and then they crossed over. Every day the owners had to keep daily logs about the eating, the vomiting, is my cat having a happy day, a not happy day. What is their quality of life like and we recorded all of that information. They got a physical exam, weight and body condition score before and after. Much to my chagrin only 11 cats completed the study. Once again we are very stringent with our studies and we screened 172 cats for this study. Then 16 cats enrolled in the study in the end and 11 made it through but this kind of tells you how much work these types of clinical trials involve. The problem is that these cats could not have any other diseases that would affect their appetite. If they are hyperthyroid or if they had IBD or any other concurrent disease potentially it would confound the study results. So, because we are trying to have a proof of concept with this drug it is important that it be a really clean study. We realize that is not representative of the feline patient at large because most of my elderly feline patients have five or six diseases if not more but for the purposes of showing it scientifically it is important that they just had chronic kidney disease. So we screened a lot of cats and those 11 cats managed to make it through the study. Luckily the drug is so effective that we do get a significant effect even just with those 11 cats. What we saw was that there was a significant increase in appetite and this is coming from the daily scoring that the owners did; 91% of the cats had a weight gain when they were on the drug during the trial. Actually a lot of them lost weight during the placebo period interestingly enough. Even if they were on mirtazapine in the first part of their trial and then they went to placebo they then promptly lost the weight they had just gained; so, it kind of gives you an idea of how well they are doing in terms of keeping up their appetite and their nutrition. Also about, all of the cats who had a suboptimal body score increased their body score. Those that already seemed okay with their body score did not have a change. The other thing that we were happy to show was that there was a significant decrease in vomiting and this was not something that has ever been shown for this drug before in a veterinary species. So basically what we saw was that those cats on mirtazapine vomited much less and this cat right here, the owner was ecstatic. This cat was pretty much an every other day vomiter and it did not vomit a single time in the time that it was on mirtazapine. The owner then reported back to me later once the cat was done with the study she went back to the normal vomiting that she had.
This also has an effect, every time they vomit they lose fluid right and they feel poorly that day. That is another reason why we continued to look at other anti-vomiting medications to help out these cats because it will help with their water balance and their overall nutrition if they are not so nauseous from their disease and vomiting all the time. So that really gave us some other major important information about this particular drug.
Conclusions from mirtazapine; we now know that we have shown that mirtazapine is an effective appetite stimulant in cats and those lower doses are as effective as higher doses and have much less side effects so we always recommend starting out with that lower dose. Some cats even need less and that is when we start to get into compounding because it is not really available in a feline friendly tablet. We know that renal disease delays the clearance of mirtazapine and so we then go to going every other day with the medication as opposed to daily which is the way we use it in normal cats. We also were able to show that administration of mirtazapine in chronic kidney disease cats results in increased appetite and it results in weight gain. Although we did not continue this study out for more than three weeks it is our clinical experience that this is very, very helpful for cats that are in the end stages of their disease. My poster child for this disease is a little kitty named Chloe who lived more than a year with a creatinine of 8 before she finally passed away in her sleep and the owners were ecstatic that that was her outcome. To keep her going with a creatinine of 8, they called if meowtazapine. I keep on telling the companies that if someone ever makes this as a feline tablet they should call it meowtazapine. They really believed this is what kept her going. She kept on eating and she was bright and perky and had a good quality of life even though her creatinine was 8 for that period of time. The only other thing that we do need to watch out for is that there is an idiosyncratic liver enzyme elevation that can happen and oddly enough we had one cat in the study have this happen even though we use this drug like candy at CSU and I have never seen it in a clinical patient. I was happy to document it for the purposes of the study but it is actually really rare and it happens in people as well. So if you do see this liver enzyme elevation our recommendation is that is probably not a good drug for that particular cat. Just bear that in mind that we should recheck and ALT after starting this drug in those chronic kidney disease cats.
With that I would like to acknowledge all of the help that I have had. This is obviously not just me doing these things in terms of our research programs at Colorado State. Dr. Tracey Webb and Dr. Steve Dow in the stem cell project are the other important members of the Centre for Immune Regenerative Medicine. We basically started this centre based on the feline stem cell program and now it has blossomed quite nicely. The Winn Feline Foundation like I said was absolutely instrumental in starting this program for us and helping out and then since then we have been able to attract other donations and other support financially to keep the program moving along. Dr. Dan Gustafson is our pharmacologist and has helped me with all the pharmacokinetic information and the modeling for all the mirtazapine work. We do have a pharmacology core at Colorado State so that is really nice. Then Dr. Kathy Lunn who we had at Colorado and has since moved on to North Carolina was really instrumental, when I was a resident we were doing this work together and we were the ones that were just determined to show that mirtazapine was great. The Winn Feline Foundation funded our study that covered all of the research that I talked about there.
With that, thank you so much and I understand there will be little cards for questions and we will answer those later.
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Beginning of Dr. Moriello's Audio.
I have been a very bad MC person. I forgot to remind you about those cards on the table. They are I hope at every table (they are). Please feel free because after our second speaker I will or someone will. I think I will have helpers running around the room. It will be our version of a workout and we will grab your questions and ask the speakers to answer those questions. Please fill out the evaluation forms and folders and turn them in. For veterinarians you can pick up you RACE CE certificates on your way out at the table where you registered I believe is where they are.
Is anyone here from Oregon? That is it? Wow, how about Washington? How about Moscow? We do, we have a veterinarian here from Moscow. Welcome! Borsht, I do not know much to say. Is that, no I guess not.
I got involved with the Winn Feline Foundation, do any of you know about this cat? Or know of this cat? A couple of people say yes. We had a dog that did – are you familiar with animal assisted therapy where pets will go in to nursing homes or hospitals and in some cases help people not only to feel better but to get better. We had a dog that did that, a miniature Australian shepherd named Lucy. After, I don’t know, several years and I would come up with new things for our dog to do. We went to the rehab institute of Chicago because Lucy was a pretty small dog we were often paired with a child who might have a spinal cord injury, burns...the stories go on and on as to why these kids or adults are there. My wife came to me one day and said you know we have got to come up with something else, I am just bored. I want something else to train Lucy to do. So lord knows why I went to Toys ‘R Us and purchased a little kids piano and I thought I would train Lucy the dog to play the little kids piano. I would clicker train. I do not know how many of you are familiar with clicker training, operant conditioning, so I closed the door to the room Lucy the dog was in and I began the process of click and I would treat and click and treat and began to shape the behavior and the paw would come up a little bit and a little bit more close to the little kids piano key and a little closer. We were doing okay and I did not close the door all the way. In walked Ricky the cat.
Ricky looked at me and looked at the dog, looked at the piano and went ping, ping, ping, ping...and I thought what am I fooling around with this dog for? I had a prodigy! Ricky was a ready, in part because Ricky a devon rex cat and in part just because of the way Ricky’s individual genetics were but in part because of the way we socialized him when he was young and before me Leslie Spiller the breeder socialized him is that he loved people, loved going out to places. He was not one of those cats that was terrified of going to the veterinarian. If the carrier came out he would hop in it voluntarily. I could take him out and walk down to the drycleaner down the block or the video store when they had video stores. We would, he would be on my shoulder and I still had the harness and leash on but he was not going anywhere and we had this relationship that was amazing. We would go Petco and PetSmart and he would do recitals there and the TV crews came out. They could not believe, this was before Youtube otherwise forget about Nora the piano playing cat, this dude had it. We had this incredible relationship that I am not sure I will have with any other pet again and along the way we were in our veterinary clinic in Chicago and just doing an exam and the veterinarian said, ‘You know I am really disappointed in you Steve.’ Then I said why? He said well you do all these performances for all these other people but how about for my staff? So we went in and Ricky played the piano and then in this little small room you had all these technicians and I do not know who all the people were. I think people from down the block, I do not know, all these people were in this little room. She then began the exam and as people began to leave the room she put her stethoscope on the cat and I could tell by the look on her face something was wrong and she said go see, and she mentioned the name of a veterinary cardiologist where we lived. Ricky had hypertrophic cardiomyopathy. Now the good news is that for many years he did not know he was sick. Sometimes with this particular disease cats very much do know they are sick. They get quite sick. That was not the case with Ricky but at some point also with this disease, we treated him as we could but at some point with this disease sometimes these cats, this is what I am looking for here, these cats just drop and die as I am sure many of you are familiar with.
Have any of you ever had a cat with this yourself? Just one hand? There comes another, another and another. Yea, it is common. You know it might even be the most common cause of death of indoor cats who do not get hit by cars or chased by coyotes between the ages of about 3 or 6 or 7 when renal insufficiency and cancers and other things begin to happen. I thought this not right, so many cats die of this yet there is nothing really that can be done. That is when I went to the Winn Feline Foundation and said we need to make a difference. We need to do something about it. We have raised well over $100,000 just for the Ricky fund but we need more, not only for the Ricky fund but in general to help cats. The researcher that you heard, the one that you are about to hear they cannot do what they do without dollars so it is a plea for dollars. But it is also look what those dollars have done. You just heard an example of what dollars can do and how that makes a difference. It is the same thing with cardiomyopathy. The good news is that if you are a ragdoll or Main coon breeder you know there is a test that is not a perfect test but it is a test that is something where you can determine, inexpensively which is nice, whether that cat is carrying the gene defect or not and then make a decision as you want to on whether you are going to breed those cats or not. Anecdotally breeders are telling me for those two breeds they are seeing a bit less cardiomyopathy and that is an amazing thing. But, that is not good enough. We want to do this for all cats. Pedigreed cats or not because this disease occurs in all cats so this is a plea from me to you to help us spread the word about what we do at the Winn Feline Foundation. All of you make a difference all the time. You’re coming to this, you paid to come to this. The money that you paid goes to help cats. Most of you are with breed clubs, many of you are with breed clubs who have made a difference to help the Winn Feline Foundation. Some of your breed clubs that are here are listed in this little program that I have so thank you, thank you, thank you. The people who buy cats from you do they know about the Winn Feline Foundation? For those of you who are veterinarians or veterinary technicians, do those clients you have know about the Winn Feline Foundation and the difference we make. People need to know about us.
Thank you very much for allowing me to say that and it is an honor and a pleasure to introduce Dr. Karen Moriello. She is a clinical professor of Dermatology at the University of Wisconsin in Madison where there is the Henry Vilas Zoo which I love and of course she is at the school of veterinary medicine there. She is a 1982 graduate of the University of Illinois, College of Veterinary Medicine. Afterwards she was a small animal practitioner in Chicago for two years before starting her residency program in veterinary dermatology at the University of Florida in 1984. She joined the faculty of the School of Veterinary Medicine in 1986 and is a Diplomat of the American College of Veterinary Dermatology. She has over 25 research grants, has published over 30 scientific articles. In addition she has written over 20 review articles and 22 book chapters. That is a lot of book chapters. It is, that is a lot of work. I just did one, one so I know how much work it is! I could read to you the name of the books and what is really interesting and impressive to me, not that all of that is not, is that she worked with Dr. Sandra Newbury to co-develop a dermatology treatment and screening programs for shelters which I think is wonderful. She is the co-editor of the Journal of Veterinary Dermatology, a recipient of a lot of awards including the ACVD award for excellence, the author of three text books herself and she is here.
Help we welcome Dr. Karen Moriello.
Dr. Karen Moriello:
Wonderful! Thank you!
Alright so just a couple seconds here while I try to figure out the computer here to get, oop there is my picture.
All of those papers were just on dermatophytosis, I have done a bunch of other things. My department chairman says I cannot just be solely focused on one topic and I say why?
Alright if it is not my computer, you know I cannot work it.
Alright we are good. Off we go.
This evening I would like to thank everybody for bringing me here again. I spoke many, many years ago with my colleague Dr. Doug DeBoer. I would like to thank you all for inviting me.
You have been funding my work since 1986 when I joined the faculty at the University of Wisconsin and since that time, you want to talk about seed money. The Winn Foundation is responsible directly for taking dermatophytosis out of the dark corners of the feline world to the point now where this disease and not just by myself but with dozens of other collaborators, has actually literally changed the way this disease is seen in private practice, in clinical practices, in shelters and around the world. We have now developed not just treatments but we have actually along with Dr. Sandra Newbury who is, well I should say, this is Dr. DeBoer, he is my colleague and co-researcher, but Dr. Sandra Newbury about 10 years ago said get out of the lab we need you in shelter medicine and I said for what? She said we have a need. She and I developed the first dermatophyte treatment and screening program at the Dane County Humane Society and since then the program has now become quite national, has received worldwide recognition and I am really happy to say that she and I continue to work on things.
Another thing that I am really, really proud of with our work and I think it is important for everyone to know. It is important to know that when we have done research studies we use kittens and every kitten that comes in off the plane is usually pretty scared from liberty and they get their own veterinary student and they get to be cultivated as pets from the get go. The person hiding in the corner up over here in the front is Spouse. Spouse is directly responsible for helping me find permanent and loving homes for all of our cats. His practice before he retired made sure that all of the medical care and surgical care, necessary spaying and neutering, was done so that we could find cats and even when we ran out of money to board them their practice boarded all of our cats until they found the right perfect loving home. That is a big thing for us.
Alright, I was actually asked to speak on two topics. The first one is malassezia and the second one is ring worm. Malassezia if it could speak would say I am really tired of being second fiddle to ringworm because I am the most common superficial fungal skin disease of cats. It is true, it really is. It has pretty much been a neglected disease but it is very important. It is part of the normal fungal flora and it is under recognized and undertreated. Just like it was in dogs. Cats are always playing a little bit of catch up and I totally agree with that sentiment. What it is, is this particular disease is part of the normal flora so people ignored it and cats were itching and suffering tremendously but nobody paid attention to it and all they got were steroids. Once we got people to realize not everything that itches in cats should get a steroid we started getting diagnoses and we started getting diseases and we started getting syndromes.
What is malassezia, malassezia is a fungal organism. This is a skin cell here. These little guys here are bacteria and these big blue guys here are yeast. They look like purple circus peanuts. Normally you would think (I am very food oriented, very food oriented so you know) bacteria look like purple M&Ms and malassezia look like peanuts to me. Where they are is present all over the body but particularly in the oral cavity and in the other body orifices. You have to remember too that with the discovery of malassezia, or I am going to tell you anyway, came another little tiny discovery and that is that cats have got bacterial pyoderma or bacterial infections of the skin. It is in all of the literature and all of the text books until the most recent small animal dermatology book that cats do not have pyoderma. You know what that is a true statement. Cats do not have bacterial pyoderma like dogs do because cats are not dogs. Cats do it differently. Everything, you know, they take it from people, they put it on to dogs and they think cats should do the same thing. Well they do not, cats are subtle creatures and so are their diseases. In a cat some of the most common clinical signs of a bacterial pyoderma are just scaling or just sort of a smudgy dirtiness on the inside of their leg and you would just totally ignore this. Cats do not do it that way. One of the most common presentations that is overlooked on bacterial pyoderma in a cat and yeast overgrowth is scaling on the hair coat. Every time somebody sees or especially baby veterinary students see scaling on the hair coat of a cat they say ‘Oh I have got a really scared cat in the exam room.’ The cat is laying there purring, you know playing with his mouse and I am like I do not think so. This cat has got skin disease. It is pretty easy once you actually learn how cats do it to find out whether or not they have got a bacterial infection of the skin. Very simply if you look close at the hairs of these cats their hair is piercing the scale and so what happens is, is as that hair is growing up it pulls up the scale and then when you look at it microscopically you will see their version of bacterial pyoderma. This is what dogs do, dogs do the big thing, the peanut thing, not cats. Cats do what I call the earth and the moon so here you have got the earth which is round and these little guys are bacteria and for many years people just assumed if it was round and it was small it was a bacteria and until there was culturing done then we discovered that cats have got their own. They have their own way of doing it. They have 11 different species of malassezia and many of them are round so therefore it is easy to overlook. If you do not have the two of them in the same scope together you are going to miss it. It is really important to diagnose it because bacterial and yeast overgrowth complicate every itchy disease that cats get and many cats have been treated for diseases that are “idiopathic” when actually they have a treatable disease.
On the far left hand side you will see a cat with raised lesions which most of you recognize as what we might have called an eosinophilic plaque but now we know it to be one form of a combined bacterial and yeast infection in cats and it is intensely itchy. That cat had the disease due to flea control. You could give that cat all of the flea control in the world but that lesion is not going to go away even with steroids until you actually treat it appropriately with antibiotics. The cat on the right hand side is one that probably for many years was a poster child for the cat with psychological over-grooming disorders. The bald belly syndrome and the old, old terms of feline endocrine alopecia which we know does not exist anymore. What we now call this is symmetrical alopecia of cats and it is simply a descriptive term for any one of a number of diseases; but one of the first ones of cats to think about is does this cat have a bacterial and yeast infection of the skin? Cats simply, they are very busy they have got 23 hours a day dedicated to sleeping, they simply do not have time to sit there and lick their belly because they have got other things to do. These cats lick and over-groom because they are physically uncomfortable. It is either pain or it is something else.
This particular cat could have demodex. This cat could have malassezia and bacterial pyoderma. This cat could have food allergy. This cat could have flea allergy. This cat needs a logical workup.
Where most of you have maybe recognized yeast and bacterial overgrowth in cats or particularly just yeast has been in recurrent otitis externa in chronic otitis media in cats. Now this is a classic allergy cat. If any of you have seen the brown follicular plugging around cats with itchy ears, they itch. Cats get seasonal allergies, I know because I live with one named Henry and you can tell by the time of the year. He just starts crazy scratching at his ears, and he is just an itchy cat. This cat here had ear mites, plain old ear mites, but that got secondarily infected, and the next thing we knew is we had wild overgrowth of bacterial and yeast infection. This cat responded beautifully to treatment, but he was presented to me at 11 o’clock at night as an emergency. I said, ‘Did you guys do cytology?’ and, you know, no; medicine people, you know, if you cannot radiograph it, maybe...we do not know what it is. So, anyway, I’m like, ‘Cmon, dermatology, TPR, skin scrapings.’ So, and then we have the cats with proliferative ears and then the cats that are really important and the cats that you need to pay attention to are cats that come to you with recurrent otitis externa and chronic otitis media. In these cats, the most common cause of otitis externa in cats is undiagnosed otitis media. It takes about two years, on average, for someone to make that connection in some retrospective studies that we have done. Cats, when they get chronic otitis media or chronic otitis, everyone seems to think it is due to a polyp; it is not. Cats get pseudomonas and cats get yeast overgrowth.
Now, what you are looking at here is an otoscope, and that otoscope is attached to a cone inside of a cat’s ear and what we are doing here is...this is a Tom Cat catheter and we have gently threaded it through the ear, passed the tympanic membrane, causing a small surgical incision, and have placed it in the middle ear canal and we are flushing fluid up, and this is a very first flush from the ear and everything you are seeing there, that cloudy debris, that is malassezia. So, these cats that have got chronic infections, they may have malassezia, and it may be due to allergies, it may be due to a poorly treated ear mite infestation, which is actually one of the most common triggers, in my experience, particularly once I started working in shelters, because one of the first things you do in shelters is they will treat everybody for ear mites, but they treat them once, you know, hoping that they will get a home on the next cycle, but if they are there for more than about 30 days, it will kind of become a chronic problem, and these cats will go on to become intensely pruritic, and the next thing you know is that they have deep ear infections. These cats do very well with treatment, but they do require a middle ear flush.
Now, there is nobody in this room who has not seen some form of this, which is facial lesions in cats, particularly chin acne. Chin acne is a clinical sign; it is not a particular one diagnosis. You can have infectious causes of it. You can have this cat here, was brought to dermatology via the dentistry service, asking, ‘Do you think this cat’s unilateral lesions could be due to dental disease?’ and, by golly, it was. This cat was rubbing its face very, very badly just because it was painful, but the lesion did not go away with the dental because there was untreated infection present there.
Then, here is a cat with the true, really deep disorder, deep chin acne, or disorder of keratinization. Cats, on their chins, have got great big sebaceous glands and so when they are rubbing up against you, as most of you know, they are not just loving you, they are marking you as a territory to all other cats. Well, in some cats, these become tortuous caverns filled with debris, just giant blackheads, and these rupture, cause a lot of pain, they become secondarily infected, and this is something that is really difficult to manage and provide quality of life.
Then, there is the infamous, easy to diagnose (ha ha!) idiopathic facial disease of many of the smush-faced cats, particularly Persians, where they will get this idiopathic black debris. I do not like to believe in idiopathic diseases; I think that condemns a cat to a life without a diagnosis. Many of these cats are allergic. Many of them have got yeast and many other allergic diseases are well under control as long as the owner does a lot of treatment and control for the malassezia overgrowth. That was Silvio, and he was a purely allergic cat, and he did great.
My absolute favorite thing is cats that bite their toes and do toe-licking. My cat only does it at night because that is when we groom is at night, particularly in bed, but when the owners come in and they say, ‘Oh, my cat’s chewing his feet’ I am absolutely delighted because, generally, I know that we can find a diagnosis for it. Foot-licking in cats is, you know, generally not normal, particularly when they cause damage, but yeast and bacterial overgrowth is very common, and these cats get yeast and bacterial overgrowth underneath the nail bed. So, if you have a cat that comes in, is really itchy and you cannot figure what it is, look underneath the toenails because you may see this black debris; that is a hallmark of overgrowth, particularly of yeast and bacteria, and you can diagnose this cytologically. Many cats that have got systemic diseases, particularly diabetes mellitus, will develop concurrent yeast infections, and that becomes really problematic. That is where we get into good friends with the medicine department because they are asking us how to manage this pruritic cat that has got diabetes because we cannot give him glucocorticoids, and I’m like, ‘No problem, we got this,’ and we go ahead and we can help with that.
Now, malassezia also, unfortunately, can be a red flag for cats that have got serious skin diseases. Whenever you get malassezia, it is because there has been a change in the normal organization flora, fauna biology of the skin; something is amiss. It is not perfect; you get overgrowth and then you have disease. Well, the cat on the left has a paraneoplastic syndrome and it has a tumor and because of that, the cat is systemically ill and has widespread hair loss and that, again, triggered yeast overgrowth. The cat here has a thymoma, and this is probably one of the hallmark diseases where if you have a cat with intense scaling and a lot of yeast overgrowth, you quickly need to do a skin biopsy and work that cat up for a possible thymoma. Those are probably two of the most common types of presentations or flags for systemic illnesses.
Skin cytology is easily done in a dog with a glass slide because dogs, you know, they are a little bit easier to manage, but in a cat, it does not work that way, so you have to practice out of the big box store, and as the joke goes in dermatology for me is that I use Scotch tape and clothespins to help my diagnostics. You can easily put a piece of Scotch tape against a cat without causing any harm to anybody, stain it, and then be able to go ahead and look at the...(Computer presentation problems...Okay, this thing is haunted and it is not just me! You can help me. Oh, please help me! Let me check something. Sorry.)
Okay, so I will just keep chatting. Down at the bottom, you will see a scalpel blade and a flat skin-scraping spatula. That brings us to one point. I abhor the use of skin-scraping scalpels, excuse me, of scalpel blades in the use of cats, and that is because they are sharp. I feel that they can cause too much damage to cats, to people, and also, you know, I think it kind of looks pretty horrible taking a scalpel blade out, you know, and scraping it against the table and then use it on your patient. So, what we use are skin-scraping spatulas, which are basically weighing spatulas, and we go ahead and use those for doing both skin scrapings on cats and also for digging material out from underneath the nail beds of cats. What this allows us to do, then, is to go ahead and spread that material out onto a glass slide and view some cytology. (Computer problems...How are we doing there? I have to end the presentation for one second to take you out of it automatically forwarding. Just bear with me one second.)
I do not embrace technology. I just got a smartphone and it has been a very long two weeks.
I still like a blackboard with a piece of chalk. Okay, all right, hopefully, now...
All right, so the treatment of malassezia, or let me just go back to my toy, here. I carry pockets of these around, and every student who graduates the derm service – and we try not to fail too many of them – gets their own little spatula like a little reward, but these cost about a dollar, and they can be sterilized, and they are wonderful. Nobody gets hurt; it is great and, again, cause no harm to anybody in the exam room.
All right, now for treatment of malassezia. Malassezia causes a major disruption in the quality of everybody’s life, particularly the owner and the cat; it is very, very itchy. So, when you have a cat with really itchy malassezia overgrowth in the ears, steroids are a must because you need to provide some relief from the pruritus. Steroids also inhibit the production of oils in the ears, which allow the yeast to overgrow. Now, if you have got a cat that is itchy enough to be coming into your clinical practice and it needs some treatment and you find yeast on your diagnostics, you also need systemic antimicrobial therapy. (We are not totally done with this thing running by itself. I am glad you are liking this because this is good!) Cats also may need concurrent antimicrobial therapy. Now, we do not want to abuse antibiotics. Dermatologists have gone full circle back to before we had antibiotics, back in the dark ages, to now going with a lot of topical therapy. This works really good in cats because the number one thing in cats that is important is coat hygiene. A cat that has got a nice coat is generally a cat that is feeling pretty good and is grooming. Cats with skin disease, for a lot of reasons, have got dirty coats, matted coats; they retain a lot of hair. So, yes, you can bathe them and, actually, I find dogs a lot more troublesome to bathe than cats, personally. I would rather bathe a cat anytime, but many people do not like that idea and, for the most part, most cats would rather not do that; you know, I mean, they will do it, but they would rather not do it. What they do like, and what works really well, is to do a lot of extra grooming with them and what you can do is you can apply topical therapy to cats that they will tolerate. First, you will groom them with a flea comb and then you can just spray the flea comb with a 2% chlorhexidine solution and comb that through the cat very nicely, and that will, in itself, resolve a lot of the secondary bacterial infections, prevent the use of systemic antibiotics, you know, cats are hard and everything makes them vomit, and so, you know, many people are jumping to using injectable antibiotics in cats, which we do want to avoid.
Another product that has come out very nicely by Douxo is a chlorhexidine and climbazole mousse, and it looks just like your own hair mousse. You just shake up the can, you mousse it up, rub it all over the cat; Henry the cat, who hates everything, just looked at me and said, ‘What was that, mom? How about some more?’ and it works very, very well. So, this is generally something that is very easy to treat. One of the things about malassezia that is very important to remember is that it is caused by some type of disruption and either that is a hit and run; something came, caused a disruption, you have been left with microbial overgrowth, or it is a recurrent disease. If you successfully treat one of these, a cat with this, and it recurs, start looking down the road for what are the particular causes, and the big group is allergies.
Okay, all right, now, cutting edge stuff. Something new. For those cats with allergies and those cats that have got malassezia as a trigger and someone is going to ask someplace on a little card, ‘How many yeast are too many?’ If the cat is itchy, one yeast is too many. If a cat is itchy, I will treat them, even if I find one or two, because it is a hypersensitivity, but cats will develop allergies just like dogs do and now there is a brand new product that has just recently been licensed, and it is allergy drops. Because it is an oral liquid that we can use to desensitize cats, just like we do for allergies to pollens and molds, this is the first time we have a product available to us where we can put the malassezia antigen in it and administer it to cats, hypersensitize them, and make these recurrences a lot less. (I did not do that...okay...but, it is wonderful.)
Okay, ringworm. Hopefully, things are under more control under ringworm than malassezia here. All right, dermatophytosis. Everybody in this room knows someone with ringworm and if you would all take off your shoes and socks, I bet we could probably identify about 50% of the population here with it. I want this point to stay with you. Every single person knows someone, either that or you have got some little kid running around in your house with that and keep thinking about it. Does your...the things and all the mysteries about dermatophytosis and all the myths that we are going to talk about, you know, do they lock you up in your room until you are cured? You know, do they dip you in bleach? I mean, do they give you weird treatments? No, no, no, no. Everything that happens to people is very analogous to what goes on in cats. It is a little bit about education across the board and physicians are a little bit behind on that; we are well ahead of it.
What is all the fuss about with ringworm? Well, first of all, I want to say – and this is really an important point – is what is all the fuss about? You know, we were able to find with the very first grant that we have gotten from the Winn Foundation that Microsporum canis was not part of the normal fungal flora of cats. They were not reservoirs of infection. If you found it, it was there, and it was not supposed to be there because cats had a really bad reputation, to the point where it was recommended to get the cat out of the house because you know it is a reservoir of infection. Well, not true. There is no evidence that M. canis, like many other diseases in cats, is becoming more virulent. It is contagious and easily transmitted, but it is not life-threatening. This is a treatable and curable disease. Skin lesions usually do not cause any terrible long-term damage; you might lose a little hair, but it grows back, and it has a very, very good prognosis. With all of that said, it is exactly like many other skin diseases that we find in shelters and in private practices such as cheyletiella, sarcoptes, otodectes, fleas and ticks, and, as a matter of fact, it is probably a lot more benign than fleas and ticks because it does not transmit other diseases, but it is of importance, and that is why! It is now required. You must get everyone’s written permission to show their face and since the cat did not agree, we had to blind him, too!
So, this is disease of public health and veterinarians have to, and many of them do, from the things that I have been preaching because gosh knows I have more soapboxes in my trunk than anybody else. All the things we do for a new cat or a new kitten that is taken into our practices and our homes and that, you know, we will do dewormings and we will do a heartworm test and we will put them on flea control, and even if you miss cheyletiella and even if you miss fleas, just by the luck of what you do routinely, you will have identified and removed one of those other parasites or problems that are so similar to dermatophytosis. The thing that needs to be added now to your plan is a routine fungal culture, if you are not already doing it, because that is what we need to do to identify and screen cats at the time of adoption to make sure that they are not carrying spores or are not actively infected because this does not go over very well at all, not at all. Children are particularly susceptible because we all know that most cats never walk the first four months of their life; they live in somebody’s arms, which is perfectly fine, which is perfectly fine.
I am going to present an amount of research here; some of it is mine and some of it is my colleagues, and everyone is happy that we are talking about it. This is kind of a cool thing, an update on the transmission and the pathogenesis. The primary mode of transmission to cats of ringworm is direct cat-to-cat contact. You can have some fomite transmission, but this is the big one. Somebody actually...Bernard Mignon, a colleague of mine, developed a cat hair follicle that you could grow in cell culture, which I thought was darn cool to begin with, but then he took it one step further and then put Microsporum canis spores, infected spores, the kind that kind of drop off the cat when they have got it, onto the skin and found out that those little spores start sticking within two hours; it peaks at about six and then if there is moisture, essentially watering them, they will germinate, and they start sending down roots. So, this means, very simply, that the very best way of keeping a cat free from exposure of dermatophytosis really is keeping them away from the source and keeping them away from other cats. This is really pretty amazing, you know, within six hours.
Where do the infections start? On the thinly haired areas of the skin. Why? Because any place a cat can groom and any place it can cause any kind of obstruction to disease is going to inhibit the infection. When you look at these models, you can find positive direct exams with a Wood’s lamp and direct cytological exams within less than one week post inoculation. This was really a cool thing to find out because when Dr. DeBoer and I were doing our experimental model of infection for dermatophytes, we saw this and we thought, ooh, this was, you know, must be something just about our model, you know, just something unique to us. Well, it is not; it is unique to all cats, and it will explain a few other things about cats that have been a mystery for a while.
Okay, now, this is a giant leap of faith here. If this was 10 years ago, I would have been up here and I would have been showing you tons and tons of slides about the different clinical presentations of ringworm. That is not how I do it anymore, and this comes from working in shelters and probably looking at maybe, easily, twenty, thirty thousand cats and their cultures over these last decades with Dr. Newbury. New way to think about this disease. There are three clinical presentations and that makes it much easier. The first one is a simple infection, and this basically means the cat has a disease, but this cat or our kitten is relatively healthy, and this cat is going to respond well to therapy. It does not matter how severe the disease is on the body, but if that cat is healthy, it is going to do great because recovery is dependent upon good cell-mediated immunity, and you have got that in the cat that is healthy. In a cat that is compromised, different story. This is not a treatment challenge. So, for those of you who have got, you know, someone is going to ask me, ‘How do I treat it?’ There are a lot of different ways of treating it, but much of it depends upon, ‘Do I have a simple infection or not?’ Many, many therapies will work quite well because, literally, these cats are ‘dying to cure’ because they can. This is acute but a treatable and curable disease; it is self-curing.
Now, second type of infection is a complicated infection, and what complicates it? Well, in the grand scheme of things, it is when there is another problem present. In this one kitten here, upper respiratory disease. Immediately, that cat is complicated for so many reasons. We know topical therapy is important, but are you really going to be getting that cat wet and hypothermic. The cat has to eat; he does not want to eat. It is hard to medicate them. They may have oral ulcers, not from lime sulfur; I have never seen it from lime sulfur but from upper respiratory diseases. Maybe the cat has been a treatment failure. Maybe the owner is a nightmare to work with...lots of things. Maybe it has been referred and a lot of things have been done with it. Breed related. We now know that rex cats, for some reason, rex cats are particularly difficult to treat, more so than our long-haired cats. There is something unique about their hair coat. These represent a treatment challenge, and this is where you need to get a lot more aggressive with your treatment planning.
Okay, and then the last one, the one that kind of got us all into this in the beginning, was the lesion-free, culture-positive cat that was deemed the reservoir of infection, which does not exist. These cats that are lesion-free but culture-positive, we need to stop and think about what that means. You saw the cat. You examined the cat. You took a culture. You get your results 7 to 14 days later, and you are looking at them. Looking at those culture results is from two weeks, seven to 10 to 14 days ago. All right. Today, we do not know what that cat looks like. You have got to get that cat back in. It is not like a CBC where you can run it in 15, 20 minutes; it is a test that takes some time. So, these cats need to come back in to your clinic and based on work in shelters that we have done, and this was a shelter where I did every single culture for almost four years, and they took in 7000 cats. This is my little hands doing all those cultures, and then we would chase down every single cat, you know, Sandra and I, and we would look at them in white light, which is like this light, or a flashlight, but then used a Wood’s lamp on every single cat, and repeat the cultures.
Here is what we found: Upon examination of a cat whose initial culture was positive but reported as being lesion-free, the cats broke into two groups: Lesion-free, culture-negative. They were false positives. They were fomite carriers. Somewhere along the line between being admitted and getting their admitting culture, which could be just a few minutes, they ran across some spores, which were picked up on a toothbrush culture, and they were culture-positive. While they were in a cage getting better, they groomed, no spores. Or, the cats at that time when we looked at them had lesions, and those lesions generally tended to be in places where they were easily missed: the toes, the nose, under the hood. How many people look under the armpits of cats? It is a very, very unique area that cats and kittens will have, and they were too small to see at examination. This goes back to that first work I showed you about transmission, where, you know, within five to seven days you can have infected hairs. Unless you spend a lot of time looking at cats and have a lot of time to look at that cat, you may miss those lesions, so this is what is really, really important is to come back and repeat those cultures on those cats and particularly a Wood’s lamp.
That cat does not look very distressed to anybody in this room, okay. Maybe he has got...it looks like he has been rubbing his eyes. It can be a lot of things. You put a Wood’s lamp on him and he looks really different; you can see some glowing. A good place from years of missing things and now I know now to look is look into the bell of the ear. Remember, those spores have to defeat the skin immune system and the grooming, so where is a good place to go if you want to set up house and you are a fungal spore? In some place where a cat is not...unless he has got a buddy that is going to suck his ears clean, is in the ears, so look there. That is really helpful, and those are those little bitty ones here.
Okay, now, eating crow. Again, many years ago, if you talked to me I would have said, ‘Oh, I hate Wood’s lamps. I hate them. Fifty percent of cats are not culture-positive.’ New piece of information: I spent about 12 cups of Starbucks coffee one day chasing that little fact down to an article in the human literature where they were talking about people, and it got perpetuated to the veterinary literature that 50% of strains of Microsporum canis do not glow. Based upon my experience in shelters, a cat with Microsporum canis, active infection, untreated, always glows.
(From the audience)
Thank you! I have been looking for those nonglowing cats and I have not found them.
Dr. Karen Moriello:
No, the nonglowing cats are going to be the ones that were culture-positive, lesion-free, that were fomite carriers. Those are the ones, okay, and let’s say they got trichophyton but that is a little bit. We are talking about M canis. There have been no outbreaks of trichophytons in shelters.
So, a Wood’s lamp is an incredibly valuable tool. Lesions are easily missed in white light. Even if you are looking at a cat with any skin lesion, get that Wood’s lamp out because you would not believe what you could see with a Wood’s lamp. I am going to tell you, everybody says, ‘Oh, it is so hard, you know, the apple green.’ No, apple green is really not hard to mistake; it really is not. The hairs glow, not the scale, and if you cannot find the glowing, lift up the crusts. Now, a very, very nice woman gave me this as a gift and that is when I realized that not only do I need my glasses all the time but that the Wood’s lamp I was using without magnification was really doing me a disservice because I was missing a lot of glowing hairs and that really, really helped.
I work with a lot of shelters, I deal with a lot of outbreaks, hundreds of them. I had about 400 toothbrush cultures that I have asked my student with good eyes, you know, the 22-year-old work-study student. I said, ‘Would you please put your Wood’s lamp on these?’ and she did, and she picked up the culture-positive ones, and then I said, ‘Okay, you marked them, now go mix them all back up and put them together again, put them back in their bags.’ I went back and looked at them with a regular Wood’s lamp and then with magnification, and I could not believe how many I missed without the magnification. This was these little bitty tiny specks of glowing hairs, so even if you are a very busy person and you get your culture and you aggressively do it and you just do not see those Wood’s lamps glowing, those hairs glowing at the time of exam, take a little bit of time after you have had your coffee and, you know, during the downtime, find yourself a dark corner with your magnification, and you will be surprised at the number of glowing hairs in those bristles. They are there. They are especially there.
I love to show this one to people, particularly this is from a shelter cat, and this is a cat in a big... he was rescued from a hoarders’ organization; I should not say it was an organization, the ASPCA recognized it, right, got the cats, got me involved and said, ‘Okay, would you do the cultures?’ I said, ‘Sure, fine.’ I got some pictures out of it, but here is the cat, and this is what we look like under white light. Here is what we look like under a Wood’s lamp. Totally different story. Here is another cat. Somebody came through and said, ‘Oh, that cat’s got a flea allergy,’ but because they were under direct orders to Wood’s lamp every cat with skin lesions, different story. More than one problem going on, so Wood’s lamps are very, very, very useful.
Along comes a Wood’s lamp; what do you do with it next? You do a direct exam and, again, this has been beaten up in the literature as being a really difficult thing. It is not a difficult thing; anybody can do this. You just need a few glowing hairs, and you can easily teach yourself to do this. First of all, I want to tell everyone you do not have to go get clearing agents. You all have it; you have got mineral oil. You just need mineral oil to look at the hairs, so right away you do not have to worry about damaging your scope. You just pluck your glowing hairs out, put them in mineral oil, put a cover slip on it, and look at them. Under 10X right here, all the nice hairs that are nice and thin and very orderly are healthy. All the ones that are kind of thickened and kind of pale, those are infected. This is at 10X. First-year veterinary students, once we teach them to do this and they do a really great job with this, you know, and we do all sorts of fancy testing in practice, and so if you are not doing this because somebody told you you cannot, back up, you can do it. You guys are cat people. You can all do it. Cat people do this, and the reason it is important to do this is...this is what this hair looks like under oil, and all these little spores up in here, that are the infective spores that get in the environment. Everyone wants to know, ‘What is the fastest way of getting a diagnosis?’ This is our SNAP Test. An exam with a Wood’s lamp. You find the hairs. You look at them, and you see them abnormal; that is confirmation that there is infection, and that is as fast as you can get it, and if for some reason you cannot find your glowing hairs, your Wood’s lamp works not only on cats, it has absolutely no fear of a microscope. Just put your glowing hairs, or where you think your glowing hairs are, back onto the slide, grab your Wood’s lamp, turn the lights out, throw everybody out, take a look, and it will glow. All you then have to do is just manipulate your stage while you are looking down through it, and you will see nice, kind of blue-green glowing and then you can go ahead and look at it under regular light and see it. So, until we can get Dr. Frank’s PCR test up and running, and I have been sharing hairs with her, this is the best you have. Actually, you can do this in about 10 or 15 minutes and we will treat just based on that.
Okay, fungal cultures. I am personally a toothbrush fungal culture person because I feel you miss less, it is easier, cats actually are kind of scared, they like it. It gives you something to do when you are talking to the client and think a little bit; works great. You can buy toothbrushes for four cents each from hospitality stores, the things that supply these big organizations and hotels with toothbrushes. You can buy them online for about four cents. Everyone asks me, ‘What kind of culture medium do you like?’ It is not the brand you use but how to use it. You have to incubate it at warmer temperatures. This room temperature stuff does not work; at about 80°, it is easy to do. To make your own little incubator you just need a Playmate cooler, put a fish tank thermometer in it and a heater, and it will warm it up. It needs to be examined daily to confirm the diagnosis microscopically, and red does not mean that you are it.
So, this is Microsporum canis, the classic. This is a highly suspect culture. Microsporum canis is pale. It grows very slowly or very quickly, depending upon the isolate of it, but pale, white colonies that have a red rim of color around them as they grow are great. This is not a diagnostic test appropriate for cat practices. RapidVet-D is a screening test. If you carefully read the literature, it says put a Wood’s-lamp-positive hair on the fungal culture medium. Well, if you have got that, you might as well just do a direct exam and away you go. This is just a screening test. I am just a little opinionated on this stuff, just a ticket. The last check I do, they did a little over 100,000 cultures since starting just in shelter medicine from the receipt, so I think we are good at that.
Pillars of treatment. There are a few. The first one is reasonable confinement, and I want to stress the word ‘reasonable,’ because cats are part of a family. To an easily cleaned room, systemic and topical therapy is necessary. The two drugs I use are itraconazole and terbinafine. Decontamination and disinfection and monitoring cats weekly, and it is absolutely cost effective because we are going to talk about something called the global cost of therapy. Now, confinement means just something where you can confine the cat and make it a safe environment for the cat, a place...you know, if you have got a cat with ringworm, you have got kittens, you have probably got kittens, okay, yeah, you have got kids, too, and they are going to want to interact. That cat needs that interaction, so you need to make it someplace clean. If people wear clothes that they can change after they have played with the kitten, transmission keeps low. Spores get everywhere, so you want to make sure that they are not putting the cat in someplace terrible like the basement; keep your closet doors shut. These seem like really logical things, but you would be surprised. You want to do reasonable confinement, and another reason you want to do weekly cultures is you do not want that kitten, or that cat that is a newly adopted family member, confined anymore than they do because a caged, even though cats will clear up faster in a cage, is really not a very good place for a cat over a long period of time.
Now, treatment. Why do you need systemic and topical? If this is our glowing hair and this is the hair follicle, systemic treatment only works at the hair follicle level. That is the only place that any of the drugs work. Griseofulvin we do not use anymore because with terbinafine and with itraconazole, they are superior drugs. They only work at the hair follicle. The problem is is that those spores go up the hair and the only thing that is going to get them is a topical treatment; that is the only way it kills them, and those spores are a big problem when you are monitoring cats. Do I shave cats? I always put my favorite shaved cat down there. No, I am not an advocate of shaving cats. Comb out those broken hairs with your flea comb. Clip those cats if you have to with children’s blunt-tip scissors. If you need to use electric clippers, you need to be extraordinarily careful because I would rather have you not clip the cat than to deal with thermal burns, which happen very frequently. This glowing hair right here is what these guys are. Why do the hairs glow? They glow because the metabolite from Microsporum canis gets painted on to the hair. Why do you always have to do a fungal culture on a cat that has got glowing hairs? Because not every glowing hair is culture positive. That glowing is from the chemical, and so later during treatment you may still have glowing hairs, but that cat may be culture-negative.
What research I have been involved in? Again, seed money has led us to being able to do great studies on topical therapy and systemic therapy, looking at experimental models and field models where we have looked at many drugs, but the two that are my favorite are itraconazole and terbinafine. You can use them daily, and one of my favorite protocols is to use either one of them for 21 to 28 days along with concurrent therapy and then stop. The nice thing about itraconazole and terbinafine is they lag and they stay in the skin for several weeks afterward. There is a protocol where itraconazole is licensed in Europe for week-on, week-off therapy. They tell you just do it six weeks, is enough; that is not enough. It is not enough until the cat is cured. There is no reason to use ketoconazole on cats, makes them sick, and fluconazole was a real big interest because it was generic but right now, terbinafine, you can get 90 tablets for 10 to 12 dollars, and depending upon the cat, that can be a lot of doses, so you do not really need to even go there. Twice a week topical therapy until cured. Now, the confirmed, based on studies that we have done both in vitro, backed up in vivo in shelters and, most recently, in a very large shelter with endemic dermatophytosis that Dr. Newbury and I worked with one year to eradicate it from the shelter. The ones that we can use are lime sulfur, ketoconazole, or miconazole. Currently, right now, I have been looking at accelerated hydrogen peroxide; it is very antifungal in vitro. We have just started an in vivo test. Ketoconazole rinse and shampoo, very antifungal. Clindasol mousse, again, is very antifungal, and then terbinafine spray is absolutely great, except it is something for people, and so you spray it, people spray it on their feet, it is Lamisil spray, okay, but the problem is most people do not stick their toes in their mouths like a cat might, so I do not collar cats when I treat them topically because there is not any need to do it, but if you use terbinafine spray on a cat, you probably might have to collar them because we do not know the safety of that drug yet, but there are some other things. My feeling is that any topical therapy is better than no topical therapy on a cat.
In shelters we will use lime sulfur, we use a Rose & Garden sprayer; actually, cats do this really well. We can do 20 to 30 cats in a half an hour. The key is warm water with the lime sulfur. Cats do not like cold water, and they do really well, and you have to coat them. The thing that is really neat about lime sulfur – I know it smells, but is really neat – is that it gives off little plumes of antifungal vapors after it dries. It was originally developed to treat the Champagne grapes in Bordeaux, France, and that is what they found out. I thought, ‘Oh, this is really great!’ because I was tracing the history about lime sulfur back and, yes, it was, you know, probably one of the first organic treatments back in Roman and Greek days, but that is really where the lime sulfur mix came up that we are using now, and, again, I do not collar cats.
Here we come to another very controversial issue, of which I will not move away from: Mycological versus clinical cure. This is the same cat, only two weeks apart. Cats, I always say, you must treat them until you have two negative fungal cultures. Some cats will clinically cure before they are fungal-culture cured; that is two cultures. On the other hand, some cats will be mycologically cured before they look clinically cured. Those are the cats that come in and have had a really rough life. They have been rescued. They are being treated and they maybe have been clipped, with some mats removed, or they were not in the greatest of shape. They are culture negative but they have not directed their energy toward growing their hair coat back, so they are culture negative, they are cured, but they look kind of ratty. So, the only way to know is by fungal culture. In studies that we have done, the mean number of days to cure, when we have done weekly cultures, is between 14 and 42 days. What this means is the number of days to cure, and that date is from the second negative fungal culture. So we still have to add some days on there to finalizing it, but that means that we are getting negative fungal cultures very quickly on these cats, and I will show you why in a second. So, that is a pretty short period of time, and so we are kind of over-treating some cats, and the only way to really know if you are doing it is to do it weekly.
Here is my plea to consider going with weekly treatment. Consider the global cost of treating a cat. You need to confine them. Now, there are cat issues and family issues. We all know this. Quality of life issues are really important. Extra cleaning of the home or the facility or the cattery, very important. We do not want to have to do that anymore than we have to, and you do need to do extra cleaning for that. Oral medication, we want to use as much as we need to, but as little as possible, and we do not want to have to do anymore topical therapy than we need to because it is not pleasant for anybody. So, weekly fungal cultures provide feedback on spore counts and cure. Also, just think about this: If you are one of those people who does a culture at four weeks and then you wait for the results, and then you do another one. What are you doing in between there? Are you giving the cats drugs? Are you confining them? Are you still dipping them? What are we doing? Because it really does depend on the cat.
Another thing that has come out of my research is that it is no longer any good to say a positive culture versus a negative culture. All three of these cultures that you are looking at up there are positive, but they mean different things. This one here has a single positive culture on it. That is a single little arthrospore that I showed you, dropped onto that fungal culture plate. This one has just a few more, and this one, wow! That is a cat that is really infected where there is a lot of spores. So, when we monitor cats for treatment...this started as a research tool, and not in the DeBoer and Moriello lab, it started back in the ’50s when they were doing the original studies with guinea pigs. They found out that you had to do weekly cultures and monitor weekly cultures to look at cure rates because as infections worsened, culture numbers went up, as infections got better and the guinea pigs cured, they went down.
This is data from one of our study cats. This cat came in, he was treated, and he was Wood’s positive and direct positive. After seven days, he – we call this a P3 because he had more than 10 colonies – was still a P3. Within week two, he was down, over here, to less than 10 colonies. By week three, he had one to four colonies, and then by week four, was no growth, and then continued on with no growth. So, we are culturing them weekly. I can tell this client, I can tell this shelter, I can tell whomever I am reporting to, this cat is getting better. I can see this going down the road. I can tell you this. If I was somebody who was going to go, and my rule of thumb was, I am not going culture the cat maybe until, you know, maybe week six because I have seen that in the literature. So you get your first culture at week six, well, guess what? You have missed a couple of weeks where that cat was already cured. You have really overtreated him. Now you have got to wait another couple of weeks to get another culture. You are going to be treating that cat, confining the cat, doing a lot more while he is already cured. So, again, it is really the only way you can do it is to go with weekly treatment and when you add up all of those costs, it is cheaper. When you are in a shelter, the cost of one fungal culture is equal to one animal care day, so, therefore, it makes it hugely, hugely important.
Now, back to this, back to your friends, maybe not you, with ringworm, and back to your cat with ringworm. Everybody knows something. My recent work has been on decontamination and I guess I just want to tell you, just make a, you know, explain what is contamination. Here is our kitten with ringworm. Hair falls into the environment. That is what it looks like microscopically. This is what it might look like under a Wood’s lamp, and under a microscope here, but these little hairs and these little spores end up on fungal culture plates. What does that do? If the environment is contaminated, the cat is going to roll around and get dusty. Just take out...just everybody please, go home with a flashlight, find your cat, turn the light on; you are going to see dust. That cat is going to have spores stuck in dust. Spores like dust, and what can happen is you will get a false positive test.
The major problem with environmental contamination is not transmission of the disease. This is the only documented case report I could find of transmission from environment to a kid. I have seen it in shelters when people have grabbed one infected cat and then grabbed another, or have used a contaminated clipper, but just a cat in an environment, even in our experimental studies where the rooms were contaminated, they did not get infected. They needed cat-to-cat transmission. So, the problem with environmental contamination is it makes it difficult to interpret when your cat has a cure, and you end up overtreating.
So, myth-busting. This is in a book, out of a textbook, for veterinarians. Once you get in the house, you cannot get rid of it. That is so false, and this is what really freaks clients out is you tell them the cat, that, you know, there is environmental contamination and their mind immediately goes to...what is on TV right now? The black mold of everything. All these terrible storms, all this terrible damage. Ringworm spores just lay on the ground like M&M’s, waiting to get swept up. They cannot multiply in the wood, in the environment, anywhere. They cannot do that. They can only live in cat hair, so unless you are living in a house with cat hair like the old lady who lives in a shoe, it is not going to multiply! It is just going to lay there. So this is a myth, that it invades things. So, it is very, very good on our part.
Another thing. It is in the air. People come to me and they say, ‘Oh, I’m breathing it. I need to wear a mask.’ I’m like, ‘No, nope, you don’t, mm-mm, no.’ In a field study where I was absolutely convinced that maybe, that they were blowing around, I went in there. There were 30 cats in a shelter treatment area. I put fungal culture plates over these vents and as the hairs were all blowing around, I was expecting that all my culture plates would grow positive. They did not and I was like, ‘Aw, didn’t work.’ I did it again and it did not again and did not again, and then finally I said, ‘Where is this stuff going?’ and I thought, ‘Why don’t we check the furnace filter?’ By golly, that furnace filter was positive, so your furnace filters are trapping your hairs. So, moral of the story, get a good furnace filter. So, that is great.
So, the evidence to date: Environmental control for ringworm needs to be constant and continual; if it is all you can do, it is tremendously important. The two most important steps, the two important steps, are aggressive mechanical removal of hairs and debris and then scrubbing it, like Grandma used to do. Aggressive scrubbing with a detergent and then rinsing it clean with water. There is no disinfectant that is a one-step disinfectant; that is all malarkey. If you read the labels, it always says clean it, clean it, do an aggressive cleaning, not effective in organic material. There is no such thing as a one-step cleaner, and you have to rinse them because most disinfectants are inactivated by detergent residue.
Okay, so mechanical removal. In this particular shelter, what we did is we, over eight weeks, we monitored 20 different sites, and we had almost up to 30 cats at one time, and all they did was exactly what I told them, was mechanical removal, washing them, twice weekly disinfection with a 1:100 dilution of bleach and, at the very most, we had four sites that were positive. The week that we had four sites that were positive was because somebody forgot to change the gown that they were wearing when they were dipping cats. So, we did not have it blowing around; we did not have it anywhere. That is I think is pretty convincing, but that was not good enough, so I made my resident, Dr. Bill Oldenhoff, do a weekly one-year surveillance at a veterinary teaching hospital, so a veterinary clinic, and we did random weekly cultures, 14 different sites; he will tell you 1800 cultures later and a little bit of wrist pain, and what we found was that routine mechanical cleaning of the floor throughout the day and twice weekly cleaning and the use of quaternary ammonium cleaner revealed rare isolation of spores. However, the dermatology room happened to be the hot spot, so if any one place was to be positive, it was our room, and that was because the place where the cats were coming in for this was the hot spot. So, it was not throughout the whole hospital. So, anytime we had a cat that was positive, we chased that cat all through the hospital no matter where he went and did cultures to look to see whether or not this cat was spreading spores, and it was not. As long as we kept him wrapped in a towel, he was good to go.
Now, for ringworm cleaning, make your life easier; mechanical removal, get friendly things. I like this stuff by the 3M Easy Trap, and I do not get any money from them; I have asked them for money. They will not give me any money. They will not give me any samples, and I tell them I do this. This stuff is like sticky paper. It is like Post-it notes, and it looks just like a Swiffer and it picks up debris everywhere, and it is very, very nice to do it, but sweeping, if you use a vacuum cleaner, do not use anything where it blows out like a Shop-Vac; use something with a cup when you do not have a bag to do it with, but sweeping and the swiffering works great and then, washing.
This is a room in a shelter where there were a bunch of kittens that had ringworm, and we were concerned about upper respiratory disease. We completely decontaminated this room simply by washing everything with soap and water, and it was amazing, so mechanical removing did it. Again, I have already coached about there is no such thing as a one-step cleaner and disinfectant, and a lot of companies will sell that to you and try to, and do not believe it, but, basically, mechanical removal, because these ringworm spores fall to the ground, they stick to dust, and, therefore, they can be removed. They are just like M&M’s. Then, get friendly cleaning. Remember the business about moisture? You do not want wet, moisture, and mops all over your clinic, so what I really like, again, 3M – and again they will not give this to me – they have these things called flat mops. They are very nice because what you do is, it is a reusable, and so this is a big state to be eco-friendly in, pads that will really scrub up and clean an area. They come with these little tiny, you just squeeze it out, containers where you can put your detergent in there and clean the area, then you can rip off that little Velcro flat mop, put your disinfectant in there and then go right over it, and it is really easy. You could buy it on Amazon.com for about, I think it was like $1.19 the last time I looked, and they are really, really easy to use, so if you have got a clinic, then this is so much nicer than that big, dirty bucket of water, and that big, dirty bucket of water is bad.
In some of the early studies that I did where I really beat up a lot of disinfectants, it is because what we did them on was very dirty environments. We used them on contaminated areas, so the only thing that came up positive was formalin and undiluted bleach. Well, neither of those are really kind of friendly to be using, so let’s talk about bleach. I have concerns about bleach, as most of you do; pet and human health concerns. It needs to be fresh because it breaks down and watch out for purchase expiration dates. I once had a project go completely sideways because the bleach we were using for our positive control was expired. So you have to buy it fresh. Who would think bleach would have an expiration date, just like soda pop. It needs to be mixed fresh and more frequently if it is in a spray bottle, the bottle needs to be dark. Less effective if there is detergent residue, and it can be totally ineffective if there is too robust a challenge, so if you go and spritz it on an area that is very dirty, it will not work. It will not penetrate hairs. In what concentration? When the area looks clean, is absolutely clean, you can use it safely at 1:100.
Research on disinfectants. Many of the things that are labeled as antifungal, they use trichophyton, and so what we did find is, I had another very industrious research student and what we did is, we thought, ‘Let’s go ahead and let’s look at those things that are over the counter that are available for use for people,’ and we looked at a number of products. What we actually did is we took small swatches of cloth and we contaminated them with a little over 5000 infected spores, which is a lot, and then went ahead and sprayed them with the products that were labeled there, including Trifectant, which I beat up a lot in previous studies, and sprayed them once to kind of mimic somebody doing a spritz and then five times to mimic a thorough application. What we found was that a lot of the products that are available to you over the counter are extraordinarily antifungal when used aggressively and thoroughly, and they are ready to mix. One of the latest products that many people are probably using is accelerated hydrogen peroxide or Accel. This is something I really like because it is very good against staphylococcal bacteria, which is a big problem in a lot of practices.
For those of you who use clippers, you are probably wondering if I have done anything with clippers; nothing escapes me, and I can tell you that if you can mechanically remove all of the hair and spores from your clippers and then use Clippercide and spray them and follow the instructions, which is to spray it real thoroughly, let it sit for 10 minutes, you will absolutely be able to kill spores. If you are traveling to various shows and that, you should never leave home without your Accel spray and Accel wipes because they are very effective against...Accel wipes will help you remove a lot of...mechanical removal of debris and Accel for 10 minutes on an area is antifungal.
Now, to laundry. That is my latest project funded by the Winn Foundation. This is not my basement, but the original studies were done in my basement because I thought I cannot do this study if I will not ask people to clean...let me back up. If I am going to tell people how to clean something, I better be able and willing to do it in my own house, and so my husband will attest to our basement being a laboratory. What we did is we looked at various different ways to find out what is the most dangerous kind of laundry combination you can have with infected spores. So, what we did is, we took infected – I took, he watched and made coffee – and we did various combinations, and what we found is that if you really want to enhance the spread of contaminated spores from a wet contaminated area to laundry that is uncontaminated, make sure everything is wet. Wet, infected material on wet towels, we had 90% contamination. The next one, again, if the infected towel was dry but the uncontaminated areas were wet, 50%, and, again, if the towels were clean and uninfected but wet, infected; dry-dry was the least one. I would pretty much tell you probably the safest thing to do is if you have got contaminated material, bag it up, wash it as quick as you can, do not keep it in contact with anything else. In humans, they suspect that over 50% of transmission of fungus, of an athlete’s foot fungus, from one member or family member occurs because of the laundry.
Okay, and so then, on the second part, we are not done with all of the study, we still have the carpeting and that is in progress, but we looked at, ‘Hey, what about laundry?’; you know, what temperature do we need to wash things in? So, what we did is we took macerated infected hairs, so we took a bunch of infected hairs, grind them up, not in the kitchen, obviously – some things are done in a laboratory – took something about this size that was either made of linen, denim, or terry cloth, and gave it a contamination of 5000 infected spores per piece and then did 100 of them. I washed things in cold water, cold water with bleach, then cold water with bleach and then a dryer, and then repeated it again with hot water. The cold water was whatever was cold coming out of my particular basement and hot water, we had to crank up the hot water pretty hot to get it to 60° centigrade, which is the recommended temperature for human laundry, and what did we find? Well, we found that, basically, washing things worked pretty darn well to get rid, just plain old washing with a detergent, really removes infected spores, and in those things, we only...in the first study, with just cold water and detergent, we found only 16 incidences where things were still positive, and, again, it was just one to four colonies per plate, and the hardest thing to wash was denim. Take-home message: Do not wear denim around infected cats. When we used bleach and cold water, there was no transfer to uninfected material, because I threw some uninfected towels in there, and no contamination, so bleach is a pretty good thing to use. Hot water and detergent, we just had two positive transfers and, again, it was on denim. The problem was that although the hot water, which is about 140° Fahrenheit – I am almost done – is very, very antifungal. It does not stay that temperature in the laundry tub, so you really have to make it hot, but if you add bleach to it, you are in good shape. So, basically, there was also no contamination. So, the best recommendation – and here is where I am ending – is, best recommendations for washing: Keep it separate. You can use hot or cold water, use bleach, hand washables, which should be the only reason why you would wash something in cold water and not use bleach, wash them several times, and line-dry them. Again, you are looking at 140°, so you are going to have to take a meat thermometer to do that testing, but it is very, very hard to maintain it. Routine washing with a half a cup of bleach was very effective, and I think that should bring a lot of comfort to people to know that you can just wash things and get rid of infected spores. So, thank you very much and thank you for letting me go overtime.
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Beginning of Question and Answer Audio.
Question and Answer Session:
We will get the card. I will get the card from you. Give me one second here until I get myself...
Is Joan Miller in the room? I do not think she is, but it does not much matter. Would you help me thank Joan Miller because Joan Miller, who I know is here in the building, created this event all those years ago; it was her idea.
And, you guys, are you okay sharing this microphone or would you like one of this because I could probably talk loud enough for everyone to hear.
Dr. Karen Moriello:
We are okay sharing. We are used to shared equipment.
Hold on one second. All right, also the videos are going to be made available. I hope all of you, I know all of you are on Facebook, right? Of course, and on Facebook, for those who are, I hope you find the Winn Feline Foundation Facebook page, and we are going to, on our website or another website, we are going to post the video of what was done. I mentioned one of the fancy videographers. The other is Otto Wolf; thank you very much for the work that you do, Otto, for the Winn Foundation.
All right, I do not understand this one. All right, I will ask if you have any other cards, if you could as I walk around and here is one.
Thank Maureen Walsh our executive director!
I want to...Oh, gosh. A veterinarian apparently wrote this because I cannot read it. ‘Is Trifectant effective?’ Is that what the question is? Have I got that right? Am I saying this right?
Dr. Karen Moriello:
All right, so Trifectant is effective as an antifungal agent if the surface is properly cleaned, and my recommendation is to use twice the recommended concentration for, if you use it, just double the dose because it has got two doses on there, on the bottle or on the tablet. So it is very effective. Actually, it is a good product to use because it is effective against a lot of other things, so my recent work has shown that it is effective when used on a precleaned surface.
Do not move. ‘Can putting things in a hot attic kill spores?’
Dr. Karen Moriello:
Actually, another experiment gone awry because a bunch of toothbrushes got left in a car over a very hot weekend, but the inside, excuse me, the ambient temperature was over 95°. The car was in the sun; it was there for 72 hours, so if we can just do the math – and I know that that is available someplace on the Internet – we can figure out that temperature, it might work. I guess it depends upon what the items are; if they are family heirlooms and that, I would say that you can give it a try, but you would have to culture it to be sure. Otherwise, just wash them.
(From the audience)
The sturdy tents that we use at shows are difficult to wash.
Dr. Karen Moriello:
I am sorry, the what?
(From the audience)
The sturdy tents that we use at a show are difficult to wash. So, I was wondering if just heating is hot enough.
Dr. Karen Moriello:
The sturdy products, what is it made of? I guess I am not familiar.
(From the audience)
Nylon coated in polyester, I am an East Coast vendor for Sturdy Products. Usually what I tell people is to wash them. You can put them in your shower or bathtub and soak them --- and take them out on your deck and hose them down and if you wash them in detergent and then rinse, rinse, rinse, and leave them out in the sun to dry...
Dr. Karen Moriello:
If they are made of nylon?
(From the audience)
Oh, no. It is a 600 denier vinyl-coated polyester.
Dr. Karen Moriello:
So I would vacuum them up. I would scrub them up with a scrub brush and soap and water. I would rinse them. No?
(From the audience)
No, a couple of things: You cannot use bleach on them because it degrades the vinyl coating and also a scrub brush degrades the vinyl coating. I usually tell people to use a soft sponge, you cannot use a scrubby sponge, either, but a sponge or like a washcloth.
Dr. Karen Moriello:
So just repeatedly wash them with hot soapy water, rinse them off, and as far as disinfectants go, you would have to color test the side to see if it is going to damage it or not. Accelerated hydrogen peroxide is the hot new thing, but I am going to tell you, it does bleach everything just as bleach does. So, I would have to test materials to see which of those products would work, to see if it damages it, but scrubbing...the two most important things: Mechanical removal of debris, even if you have to, you know, dust them off and hose them off, and then soap and water are the big things. Hot, soapy water.
Wood’s lamp question?
Dr. Karen Moriello:
‘Are there inexpensive battery-operated Wood’s lamps?’
Dr. Karen Moriello:
There are, and do not use them because they are a different type of wavelength. Unfortunately, you do need to use the commercial brands that are recommended for Wood’s lamps. I do not know if I put a link in there. Another thing about Wood’s lamps is that as long as they are not flickering, they are good to go. You do not have to let them sit and warm up for 10 minutes.
This question is that Sphynx cats, and I have a Devon Rex, so I will add Devon Rex to this, too, have lots of black discharge in their nail beds. It is kind of normal for those cats. Or is it?
Dr. Karen Moriello:
No, it is normal. I mean, it is normal because, basically, no offense, guys, but we took the hair off, which is normal, we made a breed and we are all happy with it and that is fine, but these cats...I took out Moe and Larry Lions which are two of my favorite cats that were Sphynx cats, and they were wonderful with bathing. They were the two cats that we did a lot of just bubble bathing and bathing to remove malassezia from their skin. We knew how often we needed to bathe them because they would start getting a little bit itchy, and as soon as they were itchy, their malassezia counts went up, and then we were able to go ahead and put them into remission and we did not have to keep using itraconazole on them.
Speaking of which, itraconazole is changing how liver and kidneys are working. I think maybe a word is rubbed out. Okay, okay Yeah, yeah. ‘So how important is it to use itraconazole?’ Are there any adverse reactions, in general?’
Dr. Karen Moriello:
There is no such thing as a totally safe drug. Itraconazole, we have done a study where we have looked at measuring liver enzymes at the beginning and at the end of 21 days of itraconazole in cats in a shelter that were just deemed healthy by a physical examination. There were elevations in liver enzymes, but none of the cats were out of the normal range. In treating cats for 10 years in that shelter, which were probably approaching over 1000, we have never had to take one cat off of therapy because of adverse effects. With that said, I am sure that the internists will tell me of cats with idiosyncratic reactions to itraconazole and hepatotoxicity. Yes, it can happen, but we are talking about using lower doses, and one of the reasons I am a big advocate of weekly culturing is because you use as little as possible, and that is why I like the 21-day pulse therapy.
I will read the next question, but before I do, does anyone else have any other questions that I could add to my pile here? Sure, thank you. ‘Is fluconazole effective against...’ Does the drug work? I think is what they are asking.
Dr. Karen Moriello:
Fluconazole? Yes, fluconazole is effective but at 10 mg/kg, and when we looked at it compared to itraconazole, it took longer to cure than with itraconazole. It was not statistically significant, but to me, anything that takes longer is clinically significant. Now that terbinafine is available as a generic, you do not have to worry about that. The problem with terbinafine is it can make cats vomit, so you do need to coat those tablets with a little bit of oil and make sure you give it with food, but that is probably the biggest downside of terbinafine.
Dr. Qimby for you finally!
Dr. Jessica Quimby:
Well, there is half another stack-up here, you know.
Oh, All right. That is my fault!
Dr. Jessica Quimby:
That is okay.
I was wondering. I knew there were questions for you. I am so sorry! All right. ‘What other appetite stimulants might work aside from liver or tuna or salmon?’ It does not say whether tuna or salmon here; I added that.
Dr. Jessica Quimby:
You mean in terms of food additives or...?
Dr. Jessica Quimby:
Well, that is a good question. So, in terms of trying to enhance the appetite. Actually, one of the things that we try to do is different types of food or to think about the cat’s state of nausea, actually, so if the cat is nauseous, sometimes warming the food is actually a bad thing, so food served cold may be better, or vice versa. Elderly cats do not smell well, so sometimes warming the food does work. Different consistencies of food, adding water to the food, not adding water to the food, different types of kibble, those are all things that we recommend owners try in terms of enhancing appetite. Also, some cats really like FortiFlora and it has been shown to have some immunomodulatory properties, and so that is actually something we are going to be looking at in another clinical study is that. So those types of things can help out with just making the food a little bit more appetizing. If we have a cat in a negative energy balance, actually, a/d, a small amount of a/d mixed into the other diet, is something we will often try as well.
Where’s Dr. Virginia Wright? It says, ‘Seems like a really good question, but I can’t...’ I apologize. I cannot quite make it out so I will let you ask.
Dr. Virginia Wright:
I am a psychiatrist. Mirtazapine.
And I need to see you! [laughter]
Dr. Virginia Wright:
Yes. Mirtazapine, it is antidepressant. In humans, it usually takes two to three weeks just to get them started and over the side effect state and one of the side effects is excitability.
So, my question is and it is not really a major appetite stimulant in humans. There is...very unlikely to stop the medication because they are gaining weight, and we do have a number of medicines that we do stop because they are gaining weight, so what I am wondering is, if you wait long enough and not just do the three-week trial, that you keep them on longer, that excitability may subside, and have you tried that?
Dr. Jessica Quimby:
This actually tends to be a very individual cat reaction, and so, first of all, I should say that, generally, this medication works in 20 minutes, so they literally are in the food bowl in 20 to 30 minutes. Those side effects, for some cats, can be significant enough that the owners would not want to wait any period of time, so if the dose is too high for them, then they do have those side effects, and sleeping is not actually an option when those side effects are happening for the owner, literally. I mean, your cat is driving you insane if they are in the excitability stage, so, honestly, I do not think it would be clinically possible. So, no one has ever taken it out to see if that is the case, if they would adjust. I mean, that is true of other medications where, if there is a side effect like sedation; for instance, some of our antiseizure medications, if the animal is sedated at first, that effect does wear off within two to three weeks. I guess the nature of the side effect is such that no one really wants to wait. Does that answer your question?
Dr. Virginia Wright:
No, because people do not want to wait, either, but they have to wait if the medicine is going to work, and excitability is one of the side effects, a very common side effect of most antidepressants but it takes two to three weeks to even get over that.
Dr. Jessica Quimby:
Usually what we do is we lower the dose, and it is still effective as an appetite stimulant, but they do not experience the excitability as much.
‘Is a Wood’s lamp different than a black light? Are there some Wood’s lamps that are better than others?’
Dr. Karen Moriello:
Wood’s lamps: The black light is just a term for any kind of a light with a filter that gives you sort of that blue-green, kind of off-white color. What you want is something that has between 200 and 400 nanometers of light spectrum. So, yes, there are some Wood’s lamps. So, what you want to do is when you want to buy your Wood’s lamp, you want to buy a Wood’s lamp that is used in clinical dermatology. Some Wood’s lamps are just, for instance, Wood’s lamps on CSI looking for different body fluids are of a different frequency than for looking for other hair and skin. So, the veterinary ones that are out there are usually the hand-held ones, and I can give somebody, whoever is asking for that, the link to it. I would have to go back to the slide to actually find that particular one, but, yeah.
And the last question, the final question! ‘Were the stem cell study cats also screened for other renal treatments? Were cats getting treatments for anemia screened out of the program?’
Dr. Jessica Quimby:
So, for the stem cell studies, the cats actually can be on any chronic kidney disease treatment. They just cannot have any changes during the treatment period, because, obviously, that would affect the results of the study. So, we take anyone into the trial regardless of their current regimen of medications. Starting two weeks before the start of the study, they cannot have any changes to that regimen, so it is very important that everything stays stable during that period, and that is also part of the challenge of finding stable kitties for that period of time. We only had one cat of all the kitties we have done where we were not able to use their data because the owners stopped giving subcu fluids when they went on vacation, and the animal’s creatinine then spiked because of that and it confounded the study results. So, in general, people are very, very good about following those rules, but it does make a difference; we are very careful about that.
I do have actually one more question. Can all of you help me to thank our wonderful speakers Dr. Quimby and Dr. Moriello?
I thank you all very much for coming. Thank you.
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