Urine protein profiles in cats with cystitis are indicative of increased epithelial damage

Cystocentesis - Image from University of Minnesota CVM

Cats and urinary problems go paw in paw, from the obstruction emergency in males, to common urolithiasis. As a cat owner, it is always important to search for a medical problem before blaming behavioral issues for “accidents” in the house. There’s a whole world of disease out there that can manifest itself as litter box trouble. This article in JAVMA discusses the protein analysis of both healthy cats and those with idiopathic cystitis, urolithiasis, or a UTI.

I’ve actually been thinking about performing a similar study now that I’m at a veterinary clinic with digital records, but do not have the control or finances to have as specific inclusion criteria as this study did (each patient that met inclusion criteria had urine cultures, bladder biopsy, and additional lab work to identify components of the urine performed). The results from this simple small study (n=60) are interpreted well and not only identify a protein present in urine correlated with idiopathic cystitis, but propose a mechanism for it’s presence. Clearly simple, specific, and thorough analysis of blood/urine chemistry have been paying off well for identifying these indicators.

The protein of interest the study found was fibronectin, a protein that plays a role in creating the extracellular matrix and adhesion, and is found in abundance around all cells. This adhesion role implies that fibronectin is crucial within epithelial tissues such as those lining the bladder and urinary tract. What’s interesting is that according to the article, while fibronectin plays large roles in wound healing, blood clot formation, and tumor invasion (Lemberger Et Al., 2011), it was not found in the same high concentrations in any of the cats in the study with conditions other than idiopathic cystitis. One would expect with any inflammation or blood present there would be the same abundance of this protein, but that was not the case. The authors proposed the mechanism that, with chronic idiopathic cystitis, there is significant fibrosis in the urinary tract which damages the epithelial walls. This damage is corrected by increased expression of the fibronectin gene so that the tight junctions between epithelial cells in the cell matrix can be repaired. Thus, with an abundance of fibronectin available to repair chronic damage in the urinary tract, some of it is released and flushed out with urine.

Further study is obviously needed with a larger sample size and more variability in cases, but if the authors’ prediction is correct, fibronectin could be an indicator of epithelial damage in other areas of the body as well. I’m not sure how exactly to go about identifying localized damage, but I am interested in the role that fibronectin could play in anticipating chronic renal failure in cats, as urine chemistry will often not yield an obvious diagnosis until loss of renal function is severe.
ResearchBlogging.orgLemberger SI, Deeg CA, Hauck SM, Amann B, Hirmer S, Hartmann K, & Dorsch R (2011). Comparison of urine protein profiles in cats without urinary tract disease and cats with idiopathic cystitis, bacterial urinary tract infection, or urolithiasis. American journal of veterinary research, 72 (10), 1407-15 PMID: 21962285

Link: In thinking about the future of veterinary medicine…

The Dog Zombie just published a post describing their feelings as they finish Vet School. It’s a profound and inspiring essay, and I encourage everyone in my position, anxiously awaiting if you’ll get to attend school this year, to give it a read. I personally hope DZ will be hiring when I graduate, or even giving the commencement when I walk.

The post is titled “Navel Gazing with a Dog Zombie”

Book Review: “Horses and Horsemanship” – M.E. Ensminger (2nd edition, 1956)

Haha! Finally finished another book in my stack of things I’m halfway through reading. Sorry for the delay in posts, I started a new job and was focusing on doing well for finals, still waiting to hear if vet school is going to offer me a spot as an alternate this year.

So I picked up Horses and Horsemanship at a used bookstore here in Corvallis looking for a simple review of different breeds and styles of riding. I’ve mentioned before that I wasn’t raised to be a horse person, but I do like horses, and plan on working with them and the people who own them in the future.

I realized after I bought the book that it was published in the 50’s, so much of the medicine and training techniques were well out of date. Rather than go out and buy the most recent addition, I thought it would be fun reading the perspective’s from that time period, and that the history, breed descriptions, and event descriptions would be pretty much the same (been right so far).

Most interesting was the history section, which was fascinating in that it included the various European and Arabian developments of the horse and their use in agriculture and sport. It also included the authors unique views from 1956, in which he foresaw a renaissance of the horse for sport use as it was replaced by automobiles and tractors. I myself was amazed that the tipping point of more tractors than horses for agricultural use occurred only shortly after WWI, my own mother who grew up on a dairy mentioned to me that it was about that time that her father got his tractor. His predictions turned out to be correct, as we have seen growth in the numbers of horses in the US since the 60’s, with no additional use in agriculture.

The book was fun to read, and extremely beneficial to someone like me who needed a quick overview of common horse breeds, history, and descriptions of various racing sports. I would recommend picking up the newest edition if you’re interested in medicine and nutrition briefly covered (the genetics chapter was entertaining, as much of the information they had at the time was either incomplete, oversimplified, or proven incorrect in later years). However, it was really interesting to read about the recent history of the time, and how mechanization changed the use of the horse. I’ll leave you with a brief excerpt showing what I’m talking about.

The future of the horse and mule industry

Most people agree, horse lovers among them, that further declines in work horses and mule numbers are inevitable. But we need to take stock of our gasoline and oil supplies. Should there be another war, perhaps the retention of a goodly number of horses and mules might be in the nature of preparedness. In the final analysis, however, the dominant factors that will determine the future of the horse and mule situation are: (1) the amount of mechanization, (2) the need for the cow pony, and (3) the use of horses for recreation and sport.

Further mechanization inevitable

We new live in an atomic age. Certainly, further mechanization in this era is inevitable. Some manufacturers even go so far as to predict that it is only a matter of time when the farm horse will be driven into permanent oblivion. In the thinking of these machine enthusiasts, this time only awaits the ingenuity of man in perfecting more and better adapted machines that will operate with greater economy.

(Ensminger, 43)

Clearly, Ensminger wouldn’t even be able to fathom the world we live in today where so many people have never even seen a horse in person. I do agree that the cow pony is still unbeatable in it’s unique purpose. Though I think ATV’s provide an excellent tool as well.

Even the Army’s famous little jeep does not appear sufficiently versatile for use in roping a steer on the range. (Ensminger, 43)

 

Ensminger, M. E. Horses and Horsemanship. 2nd ed. Danville: Interstate Printers and, 1956. Print.

New Research: An examination of working senior horses

Just letting you all know that I’ve added another paper to the Articles by A.J. Bouck page on the site. It’s a review of the current literature concerning the exercise capacity and changes that occur as horses age. I wrote it for my Equine Exercise Physiology class here at OSU, and I think it’s a pretty good review of the surprisingly little literature available examining changes in older horses. You can read it here, and feel free to check out the other article on that page as well.

Links

Here’s another digest of great articles and blog posts I’ve come across in the last month:

Neurobonkers has an excellent discussion on the prevalence of scientific fraud.

Smaller Questions looks at the effect of circadian rhythms on immune responses.

Molecular Love talks bout the gene Pumilio 1’s role in preventing overzealous sperm apoptosis.

Animalwise talks about a couple articles that indicate that dogs can understand us, specifically being able to differentiate between nouns and verbs.

ScienceDaily has an article discussing the creation of methicillin-resistant Staph Aureus within livestock, and relevance to antibiotic use, another detailing a newly discovered prion disease that is ten times more lethal than common hoof-and-mouth disease, and one more discussing obesity’s effect on dogs’ quality of life.

ASAS had an amazing webchat talking about the politics of farm animal welfare, and what we in agriculture should be doing to keep science as well as personal ethics in the discussion. About 35 minutes long before the submitted questions. It’s an amazing lecture and raised some excellent points.

Finally, Jason Goldman has an amazing article detailing observed tool use by a captive dingo. Complete with video! Read all about it at The Thoughtful Animal.

That’s it for this round, look for another batch of links in a month or so. Also, if you want to see more blog posts backed by peer reviewed research, check the homepage of researchblogging.org, you’ll see Animal Science Review on there, as well as most of what I read outside of my usual feeds.

Badger culling in the U.K. – step one: cull badgers, step two: …?, step three: profit!

Image from BBC News

A friend of mine thought this would interest me when I last visited him, and I had him send me the links discussing badger culling in the UK to control the spread of bovine tuberculosis (Mycobacterium bovis).  In addition to having an economic impact,  bovine TB also carries a zoonotic concern. I thought I would learn more about the issue, and see what the literature says about the success of the program.

Badger culling has been a part of TB control in the United Kingdom since 1973. Despite this and other programs in place, incidence of TB has only increased during that time. In the thousands of biological and environmental risk factors that have been associated with TB infection risk, Badgers have been identified as an important reservoir and potential vectors for the disease.

The politics surrounding the issue are interesting, and provides a great case example of how public perception can be skewed for certain species. The regular players are all there: the economically invested (in this case, cattle farmers and associated industries), the scientific community, outspoken animal interest groups, a generalized public perception, and the federal government trying to cater to the majority of voters (or campaign contributors, depending on the official and your own opinion). Lets break down these players.

The Economically Invested

On this issue, everyone seems to be on board that bovine TB is a problem in the UK. The ones who really care though are cattle producers, meat and dairy processing companies, and the retail ends associated with those products. When oppositional parties want to discredit this group, we see them described as “big corporations” only concerned about the bottom line. These claims are many times true, as even the small farmer has to maintain a decent profit margin to provide for him or herself. This group tends to be less publicly oppositional, preferring to exercise their strength through advertizing, lobbying, and funding research that can help support their position. Within this issue, I wasn’t able to find any ads produced by organizations in the UK, however, I did find some farmer concerns over the issue. One was the difficulty in getting approved for a badger cull in your area, and the other was the fear of response from activist groups if they did choose to participate in the program. The position of the farm interest groups is that the spread of bovine TB is an animal welfare and economic concern, and that badger culling will be critical in suppression of the disease. Local wildlife can often aid transmission of disease; however, we have also seen blame placed incorrectly on wildlife in other situations.

Animal Interest Groups

There are many groups in the UK that advocate for Animal interests, and they’re pretty much unanimous in the opinion that culling badgers is not an effective or ethical way to combat bovine TB prevalence. However, they do have different techniques in approaching opposition. While many of them strictly condemn the practice and advertize to sway public opinion, one group (with the support of many others), Gloucestershire Wildlife Trust, has been independently vaccinating wild badgers for bovine TB. At this time they haven’t investigated the effectiveness of the vaccine itself, but rather the economical viability of the process. Their results so far have shown that it would cost more than twice as much to vaccinate an entire hectare instead of culling. Typically these same groups in other controversial situations are very politically active.

The General Public

Generally the least informed and (arguably) the most powerful, the majority of public opinion represents the majority of voters and consumers. Regarding badger culling however, most of the general public has been shown in polls to oppose the practice. Agricultural controversies are often represented by government and industry actions that don’t necessarily mirror consumer or public preference, but instead are economically viable. Whether it’s often advocated for or not, above all else the majority of the public wants inexpensive food, and that benefit often outweighs other consumer preferences (though not always). An interesting examination of the public perception of badgers is discussed within this controversy, and this argument can also apply to other similar situations we have seen over the years. BBC explored the role of badgers in popular children’s stories, and related them to other species that receive special protection even if they are not endangered. An example from the states would be our attachment to wild horses as an icon of America, and some of the debates we’ve seen surrounding not only control of wild horses, but within discussions on using horses for food. Kevin Pierce from the article sums this feeling up well:

“It’s an image issue. A lot of farmers like badgers but we also want to control the disease. If your vector spreading TB was a rat, I’m sure that there’d be no problem for farmers in securing a license to take action.”

The Government

Tasked with the burden of trying to please everyone, the federal government often responds to the loudest collective voice along with their own advisers, analysts, and ethics. In this case, we do know that the government has moved forward with culling as they have in the past. Evaluating the motivation behind these decisions is an endless discussion, whether it’s a working system or corrupt is beyond the scope of this post. Feel free to express your opinions on the process in the comments below. The best I hope for is that while looking out for my interests, my officials attempt to remain objective, and speaking of objectivity…

The Scientific Community

I’ve left us for last. The example of objectivity and a lens of evidence to weigh a cost-benefit analysis of the issue not directed by personal interests, concepts of morality, or hidden goals. Or so we would hope. As a realistic scientist who has read a lot of peer-reviewed research, I know that we are never truly objective. All funding comes from somewhere, we interpret our own results, and while we try as hard as we can to be objective, there is no perfect experimental design immune to bias. However, as creator of this site, I obviously hold research in high esteem, so lets look at some of the literature regarding the effectiveness of badger culling in curbing the spread of bovine TB.

According to the sources I found, it appears that badger culling does have a positive effect on the rates of bovine tuberculosis, but strictly within the areas the culling occurs. There’s a beneficial cumulative effect after several years of a culling program (in the reduction of detrimental effects in surrounding areas), but it isn’t necessarily lasting, cost-effective, or repeatable in different situations. The consensus amongst several studies is that localized culling actually increases TB rates in the surrounding areas, due to the displacement of normally local badger populations, and additional factors that we don’t fully understand. Given these effects, there seems to be a general consensus in the literature I viewed that at best badger culling is not a cost effective way to reduce TB transmission, and at worst contributes to the spread of disease.

Culling programs always have fierce opposition from many sources, whether it be culling sea lions to protect Columbia river salmon, culling grey wolves to protect livestock, or culling tame geese that are causing damage to city parks. There are serious concerns from conservationists and animal activists about the effectiveness of such programs that can be well founded, and the controversy surrounding badger culling in the United Kingdom is a clear example  of why these decisions would be more effective if they are backed by empirical research and economic analysis before being presented as a moral dilemma.

ResearchBlogging.org
Donnelly CA, Woodroffe R, Cox DR, Bourne J, Gettinby G, Le Fevre AM, McInerney JP, & Morrison WI (2003). Impact of localized badger culling on tuberculosis incidence in British cattle. Nature, 426 (6968), 834-7 PMID: 14634671
Donnelly CA, Wei G, Johnston WT, Cox DR, Woodroffe R, Bourne FJ, Cheeseman CL, Clifton-Hadley RS, Gettinby G, Gilks P, Jenkins HE, Le Fevre AM, McInerney JP, & Morrison WI (2007). Impacts of widespread badger culling on cattle tuberculosis: concluding analyses from a large-scale field trial. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 11 (4), 300-8 PMID: 17566777
Donnelly CA, Woodroffe R, Cox DR, Bourne FJ, Cheeseman CL, Clifton-Hadley RS, Wei G, Gettinby G, Gilks P, Jenkins H, Johnston WT, Le Fevre AM, McInerney JP, & Morrison WI (2006). Positive and negative effects of widespread badger culling on tuberculosis in cattle. Nature, 439 (7078), 843-6 PMID: 16357869

What your intoor/outdoor cat could be sharing with the local pumas

Image from Pet-peeves.org

Generally not small talk, though I imagine they might be interested in the projections for this year’s salmon run (pause for polite awkward laughter). A new article from PLoS ONE has been discussed, implying that, while direct contact may not be routine, exchange of disease between domesticated and wild cats may be fairly common.

The group of scientists involved were examining the occurrence of Toxoplasmosis, Bartonellosis, and FIV. They went out to rural Colorado and California and trapped 260 bobcats and 200 pumas to take blood samples. They also collected blood from 275 domestic cats that lived in the areas investigated, most of whom were feral and free ranging. They tested the serum of these animals for antigens that indicated infection, and ran a statistical analysis that looked at the prevalence of each disease compared to factors such as age, location, sex, and species. The data was collected over a ten year period.

I’m not going to discuss much of the wild species data, but there are some important trends for those interested in pet health, though it’s not very surprising. The researchers revealed that the prevalence of disease was much higher in domestic animals near urban areas than in those rural. This indicates that even though there is a larger number of hosts and vectors (fleas and ticks primarily) in rural areas, clearly the higher concentration of animals in urban areas and increased interactions between domestic cats and wild species (created by human expansion into undeveloped areas) plays a much larger role in the transmission of infectious diseases.

There are also some cool snippets about FIV here as well. The discussion mentions that male cats were slightly more likely to be carrying FIV, which is to be expected due to the higher rate of sex hormone driven behaviors such as roaming and fighting. The FIV strains found in the wild felids also had greater genetic diversity, suggesting that the FIV we know and vaccinate for may be a relatively new disease (at least in comparison to wild FIV serovars). The data shows that the highest combination of pathogens that the domestic cats tested positive for were FIV and Bartonellosis, and the authors mention that because Bartonellosis and FeLV infection have also been correlated in other studies, this data implies that there may be a relationship between the three. However, that relationship may be as simple as having similar risk factors.

The take home message of the study is that wild populations can serve as an important reservoir for multiple zoonotic diseases, and that exposure to this reservoir is mediated by the domestic cats we frequently come into contact with. Just one more reason to think about convincing your kitten that the outside world is scary, and that they don’t necessarily have to go check out what the big cats are doing. Feel free to check out the paper yourself, its light on jargon and easy to read. I’m actually a little disappointed to see that they collected this data over a ten year span, but chose not to do any comparison of the rates of disease from year to year. It would have been interesting to see how climate differences and population growth may have affected the number of vectors and associated risk. Additionally, because all of the samples were collected opportunistically when wild animals were trapped for other non-related studies, there was no way to ensure sampling without replacement, which may have skewed the data.

ResearchBlogging.org
Sarah N. Bevins1*, Scott Carver2, Erin E. Boydston, Lisa M. Lyren, Mat Alldredge, Kenneth A. Logan, Seth P. D. Riley, Robert N. Fisher, T. Winston Vickers, Walter Boyce, Mo Salman, Michael R. Lappin, Kevin R. Crooks, & Sue VandeWoude (2012). Three Pathogens in Sympatric Populations of Pumas, Bobcats, and Domestic Cats: Implications for Infectious Disease Transmission PLoS ONE

Cool Links

Again, here’s your digest of cool posts I’ve come across.

Ask a Vet Question Blog has some awesome pictures of a huge umbilical hernia being repaired, along with details on their procedure.

Clinicians Brief has a case report of a spay that went south due to (at the time) unknown complications.

I came across this video detailing a method of gene expression that I hadn’t learned in either my cell biology or biochemistry classes. These things are just cool.

Even cooler is this collection of images that Penn State has arranged in this virtual cat dissection. Labeled by system and a handy reference!

Last, Mutant Dragon has had a couple of great posts discussing use of antibiotics in agriculture settings and the political perspective. Spend some time browsing that blog, it’s pretty awesome.

Ovariohysterectomy versus ovariectomy, is removal of the uterus necessary?

Ah, United States’ medicine vs. European medicine, the war rages on. The battleground I’ll discuss today: elective sterilization of the female reproductive tract.

Image from Penn State Virtual Cat Dissection

This discussion came up in JAVMA recently, and I felt it warranted a look from a future vet. Granted I don’t have all the information and education here, but given that I’ve only ever seen ovariohysterectomy performed in practice, I’m interested in why we actually choose to remove the uterus as well.

Much of the article discusses the benefits gained from the simplicity of the ovariectomy procedure. With the potential to use laproscopic techniques, smaller incisions, and less manhandling of the abdominal cavity, post surgical pain and complications can be markedly reduced in both cat and dog patients. More specifically, better exposure of the ovarian pedicle due to the incision location allows for complete excision of the ovary, suggesting that the surgeon will be less likely to leave any remaining endocrine tissue.

Outside of the surgery itself, the authors discussed the often cited benefits of spaying companion animals, and how the two techniques alter the statistics. Unfortunately, there were little to no studies directly examining the incidence of these benefits when comparing groups with or without a uterus, and some of the numbers they did find were inconclusive or conflicting. I found it interesting to see some of the actual odds concerning the prevented conditions we advertize when discussing spays, the most common being mammary and uterine tumors.

The potential for mammary tumors seems to be the most significant of the spay benefits. Their overall incidence is 3.4%, with 41-53% being malignant (DeTora, 2011). If spayed before first estrus, that risk drops to 0.5%, which is huge! Almost all of the benefits from spaying come from the removal of sex hormone cycling, which seems to be largely necessary for many of these tumors to form (not surprising, as I had previously discussed how estrogen appears to have an immune boosting effect, which would promote chronic inflammation that we know to be an important risk factor for many cancers). The authors point out that as hormone cycling is prevented solely by removal of the ovaries, that all of the future medical benefits of sterilization are gained without removal of the uterus.

The only medical benefit correlated with sterilization that is obviously tied to removal of the uterus seems to be uterine neoplasia.  However, most uterine tumors are benign, with only 0.003% being malignant as well as easily treated with hysterectomy (DeTora, 2011). The authors also found no case of uterine neoplasia ever reported in a dog that had had its ovaries removed before 2 years of age, making this benefit of ovariohysterectomy moot.

While I do think that the authors wrote this commentary with an obvious preference for ovariectomy, the assumptions they made seem rational; and even though there wasn’t enough data to declare one technique superior to the other, I agree with the conclusion that the United States’ preference for ovariohysterectomy cannot be supported by the currently available evidence. However, there is no obvious disadvantage to the procedure, and whichever technique that specific surgeon is most proficient with will probably be the best choice in any situation.

 

ResearchBlogging.orgDeTora M, & McCarthy RJ (2011). Ovariohysterectomy versus ovariectomy for elective sterilization of female dogs and cats: is removal of the uterus necessary? Journal of the American Veterinary Medical Association, 239 (11), 1409-12 PMID: 22087712

Newsworthy: Veterinarians Find Infections Faster by Monitoring Nt-pCNP

"Stinger", a dog with sepsis from a bite wound. Image from Valley Center Veterinary Clinic, Valley Center, CA.

N-terminal portion of pro C-type natriuretic peptide. Try to say that one three times fast. ScienceDaily has a cool article detailing a couple new studies showing that this peptide (Nt-pCNP) could be a solid indicator of sepsis as opposed to a generalized inflammatory response. It could potentially be added to current serum chemistry analysis, or packaged as an ELISA snap for quick, in-house diagnostics for pertinent cases.

Overuse of antibiotics has been a long term problem that is being well addressed in human medicine, however they are used much more broadly and liberally in animals due to their non-prescription access (especially in large animal work), and their use as a diagnostic tool for patients who can’t speak and often can’t afford thorough diagnostics. A veterinarian who’s client is unwilling to pay for a culture will often send broad spectrum antibiotics home anyway as a less expensive option in the hopes that they will take care of the problem.

I was unable to find a chemistry profile of Nt-pCNP, but the journal article itself talks a bit about C-type natriuretic peptide. CNP is produced by vascular endothelial cells and immune system macrophages. It “inhibits microbial growth and modifies pathogenicity of microorganisms” (DeClue, 2011). The problem with looking for just CNP as an indicator of sepsis is that it has a very short half life, and tends to degrade even faster in removed serum. Therefore, the researchers decided to use Nt-pCNP as their target molecule.  Nt-pCNP is created in a 1:1 ratio with CNP as a byproduct, and is much more durable and long-lived in both the bloodstream and collected serum.

The results of the study support the hypothesis  that CNP is a good indicator of sepsis, however like anything else, it’s not ideal. CNP was shown to be a poor indicator of sepsis when the infection was peritoneal. This includes gastrointestinal perforations or other possible infections found within the peritoneum (the authors mention that using peritoneal fluid as opposed to serum from a distal point may yield better sensitivity). Taking these false negatives into account, the test had a 65.5% sensitivity, for all other origins of sepsis in the study, sensitivity was 92%. Unfortunately, there appears to be a large potential for ambiguous negatives when peritoneal infection is suspected, but it’s always important to remember to educate clients that medicine is rarely black and white. It’s nice that House is able to identify exactly what’s wrong with each of his patients every week, but most of the time, we’re just going to give them supportive care based on the most likely result. Some of the limitations of the study that the authors mentioned were the small sample size and uncontrolled natures of the ailments that may have influenced the blood chemistry (samples taken from bacterial vs. viral infections, condition as of admission, underlying secondary infection or ailment, etc.).

In the case of this test and many other lab tests, positives are very definitive and help us out, while negatives are ambiguous. This is true whether it’s a heartworm test, fine needle aspirate, fecal flotation, radiology, or any number of other diagnostic tests. Every one is a tool, and hopefully looking at Nt-pCNP levels will give us another way to confirm sepsis while our cultures are growing at the lab, or perhaps offering another faster or less expensive option that the situation necessitates.
This post was chosen as an Editor's Selection for ResearchBlogging.org
DeClue AE, Osterbur K, Bigio A, & Sharp CR (2011). Evaluation of serum NT-pCNP as a diagnostic and prognostic biomarker for sepsis in dogs. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine, 25 (3), 453-9 PMID: 21457321