[Moderator's note: This is an extra long post in what started out to be a rather short FML, so posting it all at once and holding off on any other Bob C posts for a few days. And as I was editing this, another large post came in, so forget that part about a short FML! BIG] writing. I just figure I said what I wanted to say, I usually say a lot of it, and there is not a need to argue endlessly on the subject. This time, I will respond because someone needs to address the statements, but I will only do it once and will not engage in prolonged debate. There is no arguing with people who feel their personal beliefs are sacred, and I will have nothing to do with a "religious debate" that involves stones. My name may not be Stephen, but I like ferrets to rock my world. So, enjoy this response because *I* *won't* *make* *another* *one*! This is it. That will let everyone else have the last word, and they are welcome to it. I have faith the FML membership can identify off-topic attacks and a lack of argumentative coherence, when people evade questions or ignore them, and I know Bill will bounce any post that attacks me in a personal way. In November, I'll write a series of cystine stone posts. In the meantime, I have 4 chapters to write for yet-to-be-published veterinary texts that take precedence, besides the skeletal and dental analysis I'm getting published, traveling all over the country to discuss ferret dental health and other topics, and formulating some new ferret treats and foods. I'll get back to this subject when I can. Sukie said: >Replace "decade" with "year" and it is more accurate recently for >what is being seen in just one to two of the university urolith labs >(depending on the figure used). So, it makes sense as a possible >typo (?)." Bob: No, it is not a typo. I could ask you prove your numbers with a published paper, but I won't because I know how many papers on ferrets with cystine stones have been published. I only use numbers I know are correct, which means if they aren't ones that *I* have generated, then they need to have been published. Anything else is anecdotal and untested, which has no scientific bearing in a fair and unbiased debate--which the members of this list deserve. Nonetheless, Sukie's statement is inflammatory rather than elucidative because I didn't hold the "cystine side" to the same burden of proof I am typically held to (I could delve into this subject at great length and provide documented evidence from this and other lists. Let's not go there, OK? Some sewers should never be entered, and the ferret community doesn't need that crap spread on the internet.). I gave away the benefit of the doubt on the number of cystine stones with my statement, "Even if there were hundreds of ferrets with cystine stones..." This statement more than concedes the possibility that there may be more incidences than reported in the literature, and concedes it well beyond the point to which Sukie can provide any support or evidence. The problem with Sukie's statement is that it makes it seem as if the original argument is wrong. I clearly said, "hundreds of ferrets," which is a number greater than Sukie inferred to or can prove. My point, "Even if there were hundreds of ferrets with cystine stones during that period of time, the chances of any one ferret having the disease is extremely remote" has not been refuted by her inflammatory rebuttal. We can quibble about the exact numbers, but even if there were a THOUSAND ferrets with the problem, compared to the millions of ferrets currently living in the USA, "the chances of any one ferret having the disease is extremely remote" remains a TRUE statement. If anything, Sukie's insistence that there are dozens per year only proves my point all the more, since "hundred" is the larger number. Besides, how correct IS her estimate? Is it in fact dozens of ferrets or dozens of stones? How many ferrets are actually involved? Has the increasing number of ferrets in the USA been statistically accounted for? Are these stones from a single geographic region, or randomly distributed? Was the original sampling from the vets random? Is this a representative sample? But even if it was dozens of ferrets per year, randomly sampled over a large geographic area, what does that tell us? Perhaps all we are seeing is a mistake caused by a couple of breeders, and the blip in the number of cases doesn't apply to the rest of the country. See the problem with anecdotal evidence? THAT is why I only use my own, or documented and published numbers. The rejection of anecdotal evidence has NOTHING to do with the reliability of the people making the reports; they can be extremely honest and true, but it is just that the statements cannot be scientifically verified. We cannot make ANY conclusion from them other than noting they exist, including that the incidents are increasing in number as Sukie consistently suggests. But this is all a digression. The debate point here is that I said the chances of a ferret getting a cystine stone was extremely small, that sick animals should be treated with due haste, and the remainder of the population should not be punished with possible insulinomas and other diseases linked to a high carbohydrate load diet because of an unfortunate few. I didn't hold the opposition to proving their numbers, and I have no desire to do so now. I had already conceded the number could be higher, and Sukie's insistence that the numbers could be dozens per years rather than decades was rendered moot before she even made it. Her objection does nothing to disprove my point the problem is statistically minor, which makes her rebuttal inflammatory and an appeal to emotion, NOT a scientific rebut. Sukie said: >Also, remember that most stones don't get tested; instead there is a >tendency to assume that they are going to be the more common struvite >stones. Bob: This is a problem in sampling theory. Archaeologists have to deal with this problem all the time, which is why sampling theory is such an important aspect of archaeology and has been for the last half century. The crux of the problem is if the sampling is random or not. If the sampling is random, then the numbers are likely to be true. The problem is that vets are like doctors; they don't actually randomly sample. For example, how many vets would remove a mast cell growth off a ferret's tail and send it in for microscopic testing? Not many! They know what it is, they know it is harmless, and most are unwilling to charge a client a bundle of money to prove what they already know. The same is true for doctors; I have a small number of squamous cell tumors burned off the side of my head every year; they aren't sampled, but the single one that might have been a melanoma was. Think about this for a moment. If over a period of time 100 squamous cell tumors were removed, and out of that 10 were sampled to test for melanoma, out of which 1 sample tested positive, what would the LAB see? The lab sampled ratio would be 1:10, which is a higher number than the true population ratio of 1:100. This could be interpreted as a tremendous increase of disease, simply because the sample was not randomly collected. Now, to make matters worse, what if in that same period of time the population doubled? The lab might see it as a BIG increase in disease, even if it isn't. This happens ALL the time. In the statistics for abnormal tail growths AS SEEN BY PATHOLOGY LABS, mast cell growths on tails are underestimated because they are sent in at a lower rate resulting in biased sampling. The so-called increase in numbers of cystine stones could be echoing nothing more than that vets are noticing some stones don't look "normal," and so are sending them in for analysis while discarding the "normal" looking stones. If so, this means the stones are not being randomly sampled. That could mean they are being sampled in numbers HIGHER than in the general population! I've SEEN cystine stones, as well as dozens of other types, and I might not know they are made of cystine, but I DO know they look different. My guess is most experienced vets would recognize that a cystine stone looks different. The reason is because MOST vets would see them in some breeds of dogs (and some cats) and are acquainted with them. There is not a single fragment of evidence that suggests these stones are being randomly sampled (that is, ALL stones from a single clinic during a specific period of collection are analyzed), and THAT means ANYONE suggesting the incidence is increasing in the general population is making a huge assumption. We were all taught what that means. You can dislike this argument all you want, but it doesn't change the need for a statistical study to determine if the samples are random or not. There has to be a reliable baseline in order to judge if an increase in disease is real, or just a misunderstanding of numbers. My argument has NEVER been that cystine stones are not dangerous, but that we should not let that particular problem influence how we feed the vast majority of healthy ferrets. Sukie said; >To top it off a number that get tested never wind up in urolith labs -- >just with one of the very many pathologists used by vets." Bob: This actually supports my observation that the sampling of cystine stones is probably NOT random, but that is not why I am replying to the statement. Sukie's statement is EXTREMELY condescending towards pathologists, even to the point of suggesting they are unqualified to test the stones. I think if I was a pathologist, I would be a bit upset if I read a statement like this. Having WORKED in a pathology lab, I can say without a doubt the extreme majority of pathologists with access to a polarizing microscope can easily distinguish between stone types. Even if one pathologist has a problem, which can be a possibility, they tend to run in packs like wolves, and all the others aggressively lend a hand in attacking the problem. Hell, with a microscope and a few easily obtained chemicals, I--or anyone on the FML shown what to look for-- can distinguish stone types with a bit of practice. In my urinalysis classes, I used a simple mnemonic to remind myself of what cystine crystals in urine looked like: "Stop for Cystine!" That is because cystine crystals look like transparent amber hexagonal stop signs, and they look that way in ANY species -- it's a molecular thang. Shape is dependent on molecular composition. Calcium oxalate crystals look like tetrahedrons, triple phosphate crystals (struvite, or magnesium ammonium phosphate) look like rectangular coffin lids, and uric acid crystals are rhomboid shaped, and sometimes arranged in a floral pattern. Tricalcium phosphates can also form stop sign-shaped crystals, but they can be identified because they are not birefringent while cystine crystals are moderately so (no space to explain the term; they just look different under polarized light). Sometimes the crystals are amorphous, meaning they have no definable shape. They can still be identified; add acid and if the crystal dissolves, it was probably triple phosphate. Add base and if the crystal dissolves, it was probably calcium oxalate. If you add acid and nothing happens, then add base and nothing happens, it is probably some type of protein crystal, or perhaps some other unusual type (drugs come to mind). The presence of urinary crystals doesn't mean there are stones, a degree of crystallization is normal in everyone and every animal, but if you have stones, the chances are extremely good you will see some of the crystals that built it. You might have other stone types as well, but here is a cool thing about cystinuria, the disease that causes cystine stones. Because cystine is ALWAYS present in abnormal amounts, those with the disease almost always have cystine crystals in their urine, even if they don't make stones. Now, I am not an urologist, but plop me in front of a microscope with a polarizing stage, give me small bottles of acid and base, and I could do an adequate job of identifying stones from any species, and I would know when to ask for help. A pathologist would easily out-perform my attempts. So you see, I take exception to the suppositional statement that any "one of the very many pathologists used by vets" is incapable of identifying a cystine stone. I can do it, almost anyone on the FML with a photo of the stones in front of them can do it, and I know most pathologists can do it. It isn't exactly rocket science, but I think it could be called "rock science." Sukie said, >The change in rates is why there is concern among researchers about >possible vulnerabilities been pushed; the figures changed suddenly and >markedly." Bob: You don't know this. If you did, there would be evidence in print. Where is the statistical analysis showing a sudden and marked change? Or is this just an assumption? This is an example of an inflammatory statement that biases the reader without providing adequate supporting evidence. Use the dental analysis I have been presenting as an example. Put 400 pet ferret skulls in front of you. If dental tartar is present on a tooth, you count it. You don't worry if the tooth is completely covered as opposed to half covered because skeletal rendering techniques could have flaked some off. Rather, you look at all the teeth to see a pattern. If tartar is on 1 tooth per side, call it minor, 2 teeth is moderate, 3 is extensive, and 4 or more is severe. Count both sides and divide by half. If I noted 98% of the ferret skulls had moderate or worse dental tartar, what would that mean? It really doesn't mean anything because there is no comparison. But, look at 400 black-footed ferrets, polecats, and New Zealand feral ferrets, using the exact same criteria, and see a 5% rate of dental tartar, and now, THAT is a comparison! Now you can say there is a sudden and marked increase in dental tartar when moving from a natural diet to one primarily made of kibble. There is NO such comparison in the cystine stone controversy. Maybe the increase is real, maybe it is an artifact of better observation, or maybe it is an epiphenomenon of an increase in the number of pet ferrets maintained in captivity. Without a baseline, you simply do not know, which is why that statement is inaccurate and inflammatory. It is an opinion, not a fact. Sukie said: >Are cystine stones increasing? [middle stuff edited for space] Sure. >What can't be done is to draw conclusions before the data is in. Bob: So what is Sukie doing? There has been numerous times on the FML that Sukie has stated outright that high-protein diets are a danger because of the threat of cystine stones. We have all read it. Isn't that a perfect example of drawing "conclusions before the data is in"? Of course it is!! However, the problem here goes beyond this petty example. The problem with cystine stones is one of the individual ferret, while the problem of carbohydrates in kibble is one of the ferret population as a whole. Let me explain; EVERY ferret, even those with a cystine problem, has a high protein, low carbohydrate requirement. Suggesting otherwise would be like suggesting that because some humans have IBD, their dietary requirements are likewise different. IBD sufferers have to adapt their individual diet to suit their particular circumstances, but they still need a basic set of nutrients that are unchanged because of their disease. More importantly, just because they have medical problems, it is no reason to make all humans change to a similar diet. My point, which is CONSISTENTLY missed or IGNORED, is that ferrets with cystine stones, as tragic as those circumstances are and as horrific as their health problems might be, should be treated as individuals, and such treatment should not apply to the ferret population as a whole. Maybe I should restate this 3 or 4 times in a row. Wait! I have. <sigh> Sukie said: "Of course, there is a useful, cheap, fast, and easy test which finds some (all?) of the ferrets with vulnerability to cystine stones, so it's kind of a no-brainer to do it periodically for any ferret on a high protein diet. The question is more at what stage it finds them since that it not well enough known. Just check the urine pH. If it too acidic then the ferret has a decent chance of being at risk for struvite stones so protein will need to be reduced (BUT if it is too alkaline that ferret is at risk for struvite stones and needs vegetable intake reduced). Bob: I had to read this one a few times...if the pH is too acidic the ferret is at risk of struvite stones, but if it is too alkaline, they are at risk for struvite stones? I know this is some kind of a muddled typo and you meant cystine stones in the first instance, so I will just basically ignore it. But it does beg for an explanation of urine pH, a protein diet, and stones. First of all, urine pH is NOT an adequate screening criterion for discovering which individuals can have cystine stones. It is like saying the murderer was an angry woman, so all angry women are murderers. I am white but not a racist, male but not sexist, patriotic but not Republican, and an evolutionist but not an atheist. Having acidic urine in no way means your ferret has the autosomal recessive trait that causes cystine problems. IF your ferret has been diagnosed with cystine problems, THEN pH is a somewhat adequate screening test to see if there is an individual risk for developing stones, but if your ferret does not have the cystine problem, a pH test does not mean the ferret will suddenly contract the disease. You can't catch the disease--you are born with it. Also, while cystinuric ferrets with acidic urine have a higher risk of forming stones, hydration is also an important factor; pH neutral urine with a lot of dissolved material is more risky than acidic urine diluted with a lot of water. Most crystals found in acidic urine are amorphous urates, calcium oxalate, and uric acid; if there are stones present, they are probably of these composition. Crystals generally found in alkaline urine are amorphous phosphates, triple phosphates (= struvite), calcium phosphates, calcium carbonates, and ammonium biurates. Cystine crystals are generally found in acidic urine, however, they can be found in pH neutral urine, and on rare occasions in alkaline urine (why hydration is so critically important). Cystine is an amino acid that is not as soluble in urine as most other amino acids. There are four such amino acids: Cystine, Ornithine, Lysine, and Arginine (C-O-L-A). The COLA amino acids have pH dependent solubility. For example, at pH 5.0 (moderately acidic), the saturation point of cystine is 300 mg/L, while at a pH of 7.4 (slightly basic) it is 500 mg/L. However, pH is only one factor involved in the precipitation of the COLAs; the other is how much stuff is dissolved in the urine. Urine concentration in ferrets with healthy kidneys is a factor of hydration; dehydrated ferrets have more concentrated urine, and THAT is not necessarily shown in a pH test. There are four basic requirements to making cystine stones: a) the recessive genetic trait for poor COLA renal tubule transport, b) a diet containing COLA amino acids, c) acidic urine pH, and d) poor hydration. However, the only time factors b, c, and d are a problem is in the presence of factor a. Without the genetic predisposition for COLA transportation problems in the renal yubules, cystine stones will almost never occur. Well, maybe if your diet is mostly COLA. There is one aspect of all this that is rarely mentioned, which is the pH of the urine inside the kidney. Just because the urine in the bladder is neutral or alkaline, it doesn't mean the urine in the proximal tubules is as well. The urine there tends to always have a low pH because of the presence of short chain proteins. This is why hydration seems be to a better solution for preventing stones than the modification of diet. However, it is hard to get a ferret to drink water in excess of needs, so diet tends to be the only solution for the average pet owner. You can lead a ferret to water, but you can't make him use the litter box. Because acidic, concentrated urine is not an adequate screen for cystine stones (they probably have predictive value in a ferret with the autosomal recessive trait, but cannot screen for the disease), what would be a good, cheap screen? Microscopic urinalysis of centrifuged urine sediments comes to mind. It is easy and relatively cheap and can be done in a few minutes in the vet's office. Observing hexagonal transparent yellow cystine crystals in the urine sediment would be a fairly good screen for the disease, and they would be seen even if the ferret never forms a cystine stone. Not enough urine? A small amount of sodium nitroprusside could be added; if it turns purple-red, it is a good indication cystine is present in the urine in pathological amounts, and you can do that to urine on a table. Chemical analysis of the urine is a good test; normal urine has less than 30 mg/d of cystine, while humans and animals with cystinuria can have levels greater than 250 mg/d, clearly abnormal. Cystine stones, like the crystals, are amber in color, and are radiopaque to x-rays. Chemical analysis is diagnostic. ALL are good screens and easily available to a vet, and all are better than pH. Having actually seen cystine stones, I can tell you they simply do not LOOK like struvite stones, having a different color and form. The grainy stuff in mucous might be hard to identify, but the granules are amber under the microscope. I can't believe a vet, especially one that is acquainted with what is a relatively common problem in some dog breeds, would see an amber stone and assume it was struvite. I would think the opposite would be true; they would see something that seems unusual, so would tend to send it in for analysis. Unfortunately, this is NOT random sampling, so the numbers of reported cystine stones have a very good chance of being over-estimated. It is like apples and oranges. It is easy to spot the odd apple in a bushel of oranges; they just stand out and tend to get picked first, so are sampled at a higher rate than seen in the population as a whole (the bushel). Sukie said: >Otherwise, don't draw conclusions until the study is done. That is >always wise. Bob: Again, Sukie's entire post is a drawn conclusion, as has been her past ones where the assumption is made that a high protein diet causes cystine stones and is a danger to the general ferret population. Making statements suggesting a high protein diet is dangerous to the overall population of healthy ferrets IS drawing a conclusion. Sukie said: >Are cystine stones and cystine slush very inclined to prove fatal when >they occur? Yes, uncomfortably so, and those who are saved (especially >males who are more inclined to block) have a tendency toward kidney >damage and often to needing a penile amputation and urethra rerouting. Bob: Besides being graphically inflammatory, this is a very misleading statement. In small mammals like ferrets, the risk of kidney damage and death is correlated to size. The smaller the mammal, the easier it is to block stuff up AND the faster it is to cause organ damage. Also, males have 2 to 3 times more risk of stones because of the length and kinks of the urethra. ANY stone in ferrets is a high risk, and Sukie--or anyone-- cannot show the risk of any one stone to the organs is less or more dangerous than another. It is not the composition of the stone that makes it dangerous, but the size--the bigger the stone, the better its ability to block things up. Struvite stones tend to be very big and they can grow very fast, so I would tend to argue they are MORE dangerous because of those factors, as well as being far more commonly encountered. As for the graphic imagery of an amputated penis, in this case all it does is mislead the reader into assuming cystine stones are the major culprit, but in fact that honor goes to struvite. That makes the image inflammatory and unnecessary--a clear appeal to emotion rather than to reason. It would be likewise unfair of me to graphically describe the prolonged, agonizing death of a ferret, screaming, drool dripping down their chins, and all because they developed insulinoma from eating kibble containing a high load of refined and processed carbohydrates. Or, I could be more blatant as some people do (Sukie excepted), screaming at anyone that suggests I am wrong, that I have held these screaming ferrets in my hands while they bit through their tongues during a low-blood sugar induced seizure, watching them slowly die in agony, and how dare you suggest I am wrong when the lives of ferrets are at stake, dammit! Hummm, that's not fair in a discussion, either. I have an idea. How about a simple discussion of the facts, and let's leave the inflammatory imagery off the table, ok? There is another factor involved here, which is the size of the bacula (os penis) in the male. The bacula has a urethral groove on the top that prevents the urethra from collapsing during prolonged sex, especially with a squirming partner. Ferrets like to engage in particularly prolonged, squirming sex, so that little bone has some importance. The trouble is, early neutering has a significant impact on the normal development of the bacula. They are smaller, the urethral groove is not as well developed, and the hooked tip is not always formed correctly. I suspect this is a factor in the blockages seen in male adrenal ferrets, and I wouldn't be surprised to see the problem in ferrets with cystinuria. Sukie's example may be more of a symptom of early neutering than of cystinuria. Sukie said: >It may be that centuries of milk and bread, and many decades of kibble >use on farms has had its impact of vulnerable individuals not dying off, >which increases rate of vulnerability once a higher protein diet is >tried again. Bob: Well, it wasn't exactly "centuries of milk and bread." The bread and milk diet was never very popular, and when it was given, it was always part of a diet that included a fairly nice amount of raw and cooked meats. I have investigated this diet to a degree that surpasses the category "anal-retentive." There are some aspects of this diet that many people are not aware, such as it was never very popular until the Victorian era, when the advent of transportation and mechanization decreased the costs of milk and bread. Ferrets, like any other working animal, have ALWAYS been fed foods considered economically cheap. Before milk and bread was made cheap during the industrial revolution, they were too precious to be fed to ferrets, who usually dined on rats and rabbits. So the only real places the diet was popular was in relatively rich urbanized countries--the same people who printed the books. Even so, a careful reading of the veterinary literature of the era, as well as advice offered in farm newspapers, advertising circulars, and the diet recommendations published in the ferreting books, are almost universal in condemning the diet as a main fare. Your supposition fails based on a lack of historic evidence that the bread and milk diet was as popular as you indicate. The supposition also fails because "bread" as defined in these early diets was not made of the type of flours typically used today. Most of these breads were very coarsely ground grains, NOT the finely ground and sifted stuff that we see in our kitchens today. Most modern flours lack the percentage of bran the early flours contained, making a considerable amount of historic bread indigestible to ferrets. Nor were they cooked in a heated and pressurized food extruder that denatures the carbohydrates, allowing them to be absorbed better. Much of these breads would have been in the intestines for too short of a time to allow efficient digestion, and they would have acted more in the realm of "fiber" than carbohydrates. That means the milk proteins and fats would have been the foods most easily and first digested. And guess what? That means this early diet is higher in protein and fat than a cursory look might indicate. Most of the bread and milk diets would have had less digestible carbohydrates than found in modern kibbles, which means they would supply higher proportions of protein than in typical kibbled diets. Just in case you missed it, yes, the milk and bread diet had a lot of carbohydrates which make it seem as if it is a low-protein diet, but because the digestibility of a lot of those carbohydrates was low in the ferret, the diet wasn't as low in protein as one might assume. It fails at another level as well. While a low protein diet might have helped to mask cystinuria, it wouldn't have prevented it. Plenty of ferrets with the disease would have been noted, simply because they would have been dehydrated and formed stones, REGARDLESS of diet. Cystinuria is a fairly common problem in dogs, and their diet compared to ferrets is considered too low in protein, yet they have cystine stones, as do humans. Sukie assumes stones won't occur because of a milk and bread diet, when in practice it absolutely would occur. Besides, can you imagine how acidic the urine would be on such a diet? A ferret with low pH urine from a milk diet, dehydrated from the diarrhea it invariably causes, and THAT is the makings of some hum-dinger stones. This is not the diet to mask cystinuria. We can argue the above points all day long, but there is one fatal flaw in Sukie's supposition. It fails to account for the common practice of hybridization of ferrets to polecats. This happened ALL the time (still does), which is why recent genetic studies still cannot identify the progenitor. The subject of hybridization of ferrets to polecats is mentioned in more than 90% of all the historic ferret literature. For Sukie's supposition to be true, it would mean the genetics of every system EXCEPT those for cystinuria would be normalized back to the polecat. There are a few geneticists on the FML who would argue that would be somewhat difficult. Even now, ferret-polecat crosses have been imported into the USA for color and build, so hybridization CONTINUES to this day! There HAS to be some type of evidence for Sukie's supposition to have ANY bearing on this issue, and there is none. Perhaps Sukie knows this and is offering the argument as a Strawman for me to systematically shred. I've got to find that wizard. I've heard this same argument before when some people were suggesting adrenal disease was due to breeding practices. I argued against it then for the same reasons I am arguing against this now. The argument then was that most ferrets came from an initial small population, and adrenal disease was bred into the ferrets at that point. We now know the disease is linked to neutering, especially early neutering. It is easy to blame things on poor genetics, but all you have to do is look at the numbers and know it is wrong. The numbers are simply not there for Sukie's supposition to be true. Sukie said: >The CAUSE of cystine stones in ferrets remains unknown, and is part of >what is being studied so it is premature to assume a genetic cause must >be at the base of it, let alone a shared genetic cause, though that is >certainly a strong possibility." Bob: Is there realistically ANOTHER possibility? This is one of those statements that is technically true, yet results in an erroneous message. Is the cause of cystine stones in ferrets proved? No, not yet. But come on; it has been proved in dozens of animals, and since the mechanism at fault is in the renal tubular transport system, and the problem is the same in dozens of species, how many alternatives are there? Cystine is not being efficiently transported from the urine in the renal tubules back to the bloodstream. That means there is too much cystine in the urine, and since it is not very soluble, it precipitates out and forms cystine crystals, which may or may not form stones. However, the basic problem is that the cystine is not being transported from the urine back to the bloodstream. How many things can cause that? So many different mammals have the problem, and in the ones that have been proved, it is caused by an autosomal recessive genetic trait. Are you suggesting some scientist is implying the problem in ferrets is something else, because that would be big news, as in really BIG news. Me, I'm going to use Occam's razor to cut to the truth. The simplest solution is nearly always the correct one, and that means cystinuria in ferrets is caused by the same thing that causes it in all the other species. Call me a slave to patterns, but I'd rather investigate the obvious than concentrate on something that has a higher percentage of being wrong. I guess you can call a duck a dog if you want, but how do you stop it from quacking? Sukie said: >There is also investigation into certain food types -- for instance, >the vets on at least two of these cases have noticed that the >individuals had dried peas in part of their high protein diet. Bob: Ferrets have no business consuming vegetable foods. Their teeth are not designed to render them, their stomach is not designed to digest them, and their bowel is not designed to absorb them. Ferrets are designed to eat prey, the whole prey, and nothing but the prey, so help me carnivore. It is not just the carbohydrates, which in ferrets are very bad, but also the phytochemicals found in most plants. I don't want to get into a prolonged discussion on this topic, but I do want to say that ferrets may not react to this disease in the same way as some other animals, more specifically the dog. I am under ethical constraints NOT to discuss this at length for the moment, and those that know and understand me will tell you my principles mean more to me than money, success, or friends, so don't expect me to say exactly why I know this. Nonetheless, I think I can give you an idea to part of this new thinking that ferrets with cystinuria might have to be treated differently compared to dogs or humans. Ferrets have NO, as in ZERO carbohydrate requirements. That means they have evolved the mechanisms to met their energy needs using protein (roughly 60% of energy needs) and fat (roughly 40% of energy needs). Protein is converted into glucose via gluconeogenesis; about 85-89% occurs in the liver, about 1-5% in the bowel (which is used up there), and about 10% in the kidneys. The kidneys and liver specialize in different types of amino acids that they convert into sugar. All mammals can do this, but most mammals cannot convert enough protein into sugar because that reaction is oxygen dependent, and in humans, the oxygen levels in the liver are too low. However, ferrets have a huge liver and kidneys for their body mass, and since they are small animals, they get around the oxygen hump and are able to break the rule. Carbohydrates in diet throw off this beautiful mechanism because they are preferentially used compared to protein or fat. In other words, if a ferret eats carbohydrates and protein, the carbohydrates are used for sugar BEFORE the liver starts converting protein to energy. I am sure there are already people who have had that little light over their heads switch on. If a ferret is consuming a diet of carbohydrates and proteins, the carbohydrates are use to supply energy, which means the protein levels in the blood remain higher, so there is a greater protein load for the ferret to transport across their renal tubules. If that same ferret has their carbohydrates removed, the use of the proteins for energy reduces the overall protein titer in their bloodstream. That means there are LESS proteins to transport, and a lower chance that the ferret could form cystine crystals. I've actually seen the data on this and it gave me goose bumps. There is more. Prey animals are up to 70% moisture, but kibble is less than 10%. If you need a comparison, a hardwood floor is about 10 to15% moisture and drywall is about 4 to 8%. It takes a lot of moisture to process dry kibble, which means that soon after a dry kibble diet, the ferret becomes slightly to moderately dehydrated. That means the proteins and other substances in the urine are more concentrated, so the chance of forming a cystine stone is higher. I wish I could tell you more. The subject has enthralled me to such a degree that it is almost all I think about. The point here is that the treatment of cystinuria in ferrets may not be the same as in some other species. That means a ferret is NOT a cat or a dog. I *WILL* tell you more later, once my ethical constraints have expired. Sukie said: >Again, don't draw conclusions until the study is done. Bob: Again, Sukie has already made her conclusions know to everyone on the FML, and have for sometime. She repeatedly pushes her agenda while admonishing the rest of us to remain open minded. Sukie said : >Also everyone who is interested in diet should definitely ask your vets >to let you read a copy of the Dec 2004 "Journal of Exotic Mammal >Medicine and Surgery" article by Dr. Mark Finkler on the carbohydrate- >insulinoma hypothesis which he originated. Bob: I would hardly suggest Finker originated the hypothesis; a detailed search of the literature would show he was not first in line on that one, and I don't think he would suggest he was either. However, I have a tremendous amount of respect for his abilities, and think his paper-- actually a review--is an important one that others will build on, and I do believe it is the first in the veterinary literature. I think it would have had greater impact in a journal with a broader appeal, but I think it will be read and cited for many years. Finkler's review was well balanced, giving both sides of the argument a fair representation. That is extremely important in a good discussion, which is the reason why I have used my Sunday evening to reply to Sukie's posts. Personally, it matters little to me if you find my argument is persuasive or not--at least both sides have been presented. That is unfortunately not always the case. I'm not sure dietary bias is always recognized by well meaning people; I think the IFC made a grave error by only allowing one side of the carbohydrate question to be presented at their upcoming forum. Don't get me wrong, I really, honestly like Tom Willard a lot; I have supported him and his product for a long time (for years it was the only food I would recommend), and if the guy wasn't snoozing, I would have went to work for him. But the guy simply can't discuss ferret nutrition without turning it into a Totally Ferret commercial. Recall everything he has posted here. I mean he means well, and he certainly has a great deal of confidence in his product, and loves ferrets and all that, but "Totally Ferret" tends to permeate his message. My best guess, based on historic precedent, is that people at that forum are not going to hear a balanced view of the carbohydrate problem; they will hear his side only, he will object to a high protein diet, and he will be able to argue it without risk of refutation. The IFC should have allowed an opportunity for the opposite point of view to be presented, and Finkler would have been a perfect choice. This has been a long discussion, in part because Sukie's original posts were long, and in part because you simply cannot refute a complex question with just a few sentences. I suppose I could have not addressed the issues and just repeated ad infinitum (and ad nausium) "Prove it, prove it, prove it, prove it," but that would have hardly helped explaining the reasoning behind the demand for proof. Many of Sukie's points are not points at all, just emotional diatribe and inflammatory statements. Most of her suppositions are unsubstantiated, but that is ok; this is a subject with little ferret-centered publication, so the presentation of supposition is to be expected. I admit I am tired of reading Sukie's continuous decrying of a high protein diet, while at the same time telling people not to make up their minds, or warning the opposing point of view against drawing a conclusion before the facts are in. I would suggest she follow her own advise, but I don't think anyone has to do that. I have already come to some conclusions that I might change later if refuted. I have NEVER been frightened of admitting I was wrong. I apologize to people all the time and I might end up doing it over this. But I *am* going to draw a conclusion, and I think most people will as well, just like Sukie has done. My primary concern is not if I am right or wrong. All I care about is a ferret's quality of life. That is all I care about. THAT is why this question is so damned important, why I gave up my Sunday evening to pen this response, and why I made it so long. I think Sukie has gone too far on this question. I think her ideas are somewhat beneficial to a ferret with cystine stones, but it certainly isn't beneficial to the ferret population as a whole. Sukie's basic argument, as she has presented it, is that it is important to not move to a high protein diet because a few ferrets may, might, could have cystinuria. My basic argument is, yeah, they might, but the greater good is to feed a better diet to EVERY ferret, while at the same time identifying the sick ones and treating them individually. I don't want ANY ferret to suffer. I just can't accept that it is somehow better for a ferret to die of low blood sugar while in the midst of a hypoglycemic seizure, caused by an insulinoma triggered by a diet of highly refined and processed carbohydrates, than it is to suffer from cystine stones. The symptoms of a blockage caused by cystine stones are no different than from any other stone; we CAN watch for it. Vets can do a simple screening, either of a microscope exam of urine sediments, by adding a dye to the urine, or even by chemical analysis to check cystine levels in the urine. Sick ferrets can be treated with diet and hydration, and the breeding of the line can be halted. In the meantime, we can provide a better diet for our ferret that will go a long way in preventing insulinomas and other diseases. Ok, I've said what I wanted to say. Anyone else can say anything they like, and they are more than welcome to do so. As far as my participation is concerned, this debate is finished; I've already said this stuff 3 or 4 times in the last few months, and I really don't want to continue to make the same points to people who are prejudiced against a particular viewpoint. I'm going to work on a new formulation for a softer ferret diet I have thought up that may not hurt teeth, I've got to finish some book chapters, and for Godsake, I have to play with my ferrets. Bob C talktobobc [Posted in FML issue 4977]