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Research Report: Treating Some Equine Eye Tumors with Antibiotic Mitomycin C Avoids Need for Surgery and Radiation

December 7, 2011
a donkey eye with sarcoid tumor

A sarcoid tumor on a donkey's eye would normally be treated with a highly sensitive--and high risk--radiation treatment. Now veterinarians have an alternative. This image shows the tumor before antibiotic treatment. (© University of Liverpool/Horse Trust image)

A research project funded by leading British charity The Horse Trust has found that various types of ocular tumors can be successfully treated with mitomycin C, a cytotoxic antibiotic isolated from a bacterium. Mitomycin C offers a safe and cost effective alternative to current treatment options such as surgery and radiation.

The research project was led by Fernando Malalana, while working as The Horse Trust’s Clinical Scholar in Equine Internal Medicine at the University of Liverpool. Fernando is now working as a clinician teacher in Equine Internal Medicine at the university.

Background on ocular tumors

Ocular tumors are more difficult to treat than tumors in other parts of the horse’s body because of the risk of damaging the eye. In the study, Malalana investigated the use of mitomycin C in treating ocular squamous cell carcinoma, which are the most common ocular tumors in horses, and occular sarcoids, which are skin tumors that frequently affect the eyelids .

Mitomycin C is an antibiotic isolated from a particular species of bacterium, known as Streptomyces caespitosus. It is known to have cytotoxic effects and has been used previously to treat tumors in horses before, but only in combination with surgery.

Currently, the main method of treating ocular squamous cell carcinoma is by removing the tumor surgically or with radiation. Both treatments are costly and have a number of associated risks. For example, the horse needs to be anaesthetized for surgery and there is a risk of damage or scarring to the eye.

a donkey after treatment for a sarcoid treatment on its eye at University of Liverpool

This is the same donkey as shown above, following non-invasive treatment with antibiotic.

The research

fernando malalana university of liverpool veterinary surgeon The Jurga Report

Equine internal medicine specialist Fernando Malalana led the research project at the University of Liverpool.

Fourteen horses with ocular squamous cell carcinoma, three of which were affected bilaterally, were included in the study. Mitomycin C was applied to the conjunctival sac of the affected eye; in some of the cases the treatment was combined with surgery. Malalana found that of the eight eyes treated with mitomycin C alone, clinical resolution occurred in six cases. Of the nine eyes treated with both surgery and mitomycin C, clinical resolution occurred in seven cases.

Mitomycin C was also used to treat various types of sarcoids found in the eye. Currently, the most effective treatment for occular sarcoids is radioactive wire. However, radioactive wire treatment is not ideal as it is expensive, only offered in two locations in the UK, and has potential health risks to the veterinarian applying the wire because of exposure to radioactivity.

Six horses and two donkeys with occular sarcoids, including one horse that was affected bilaterally, were treated with mitomycin C, which was injected directly into the tumour. Malalana found that of the nine nodular and fibroplastic occular sarcoids treated with the antibiotic, all were completely cleared. However, the veterinarians did not have good results with the antibiotic when treating verrucous sarcoids.

“The results of this research should offer hope to the owners of horses that have eye tumors. We have already been contacted by veterinarians from across Europe to find out more information about this treatment and hope that it will be offered to more horses with occular tumors in the future,” said Malalana.

Vets at the University of Liverpool are now testing the use of mitomycin C on other tumors that are difficult to treat surgically, including melanomas near the horse’s anus. So far, two cases have been treated, but it is too early to tell whether treatment has been successful.

Malalana’s research has been submitted to Veterinary Ophthalmology and also will appear in The Veterinary Record .

To learn more:

F.C. Malalana, D. C. Knottenbelt, S. A. McKane. Mitomycin-C, with and without surgery, for the treatment of equine ocular squamous cell carcinoma. Veterinary Record. (in press)

About The Horse Trust:

The Horse Trust, founded in 1886, is the oldest horse charity in the UK. Until a recent name change, it was known as The Home of Rest for Horses. Based at Speen, Buckinghamshire, The Horse Trust provides a place of retreat for working horses that have served their country or community and nurtures them throughout their final years. The charity also gives sanctuary to horses, ponies and donkeys that have suffered and need special treatment. The Horse Trust funds non-invasive research that advances knowledge of equine diseases, improving diagnosis and treatment and reducing suffering among equines worldwide. The charity also offers training for professionals and owners, with a focus on equine welfare and quality of life assessment.



jumping-foal-713469 by Fran Jurga
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Lameness and Age Correlation in Euthanasia of Older Horses: British Study Finds Lameness or Laminitis Reason for 36 Percent of Euthanized Geriatric Horses

October 19, 2011
© The Jurga Report Bubba beach kiss Beth Knowlton

Lameness and laminitis are given as the cause of euthanasia for 36 percent of older horses living in Great Britain. (photo © Fran Jurga)

A research project funded by equine charity The Horse Trust in Great Britain has found that lameness is the most common reason for euthanasia of geriatric horses.

This research is the first in the UK to provide data on the causes of death in geriatric horses. Although post-mortem studies have provided some data regarding causes of death, “old age” was previously reported as a common reason for the euthanasia of adult horses.

The research was carried out by Joanne Ireland, BVMS, MRCVS, of the University of Liverpool’s veterinary epidemiology group, and led by Gina Pinchbeck, BVSc, CertES, PhD, DipECVPH, MRCVS,  a Senior Lecturer in Equine Epidemiology.

Ireland surveyed horse owners who live in the North-West and Midlands areas of England and North Wales and have a horse aged 15 years or older. She followed 918 owners of geriatric horses in a cohort study; 118 mortalities were reported during the 18 month follow-up period, of which 111 were euthanized.

The researchers found that lameness was the reason for euthanasia of 24 percent of horses; an additional 12% were euthanized due to laminitis, a common cause of lameness. After lameness, colic was the next most common cause of euthanasia, with 21 percent of owners citing this as the main reason.

older horse receives hoof care from farrier as owner watches

Would a pre-emptive wellness exam help owners of older horses understand their horses' problems? The study raises some interesting questions about the welfare of the older horse. (photo © Fran Jurga)

In an earlier stage of the project, the researchers had found that half the geriatric horses surveyed suffered from lameness, but only 24 percent of owners reported the problem.

“Although lameness is common in older horses, this is the first study to quantify its contribution to their mortality,” said Dr Pinchbeck. “Owners are often missing the early signs of lameness in their horse, which means the condition isn’t being managed and may deteriorate faster. I would recommend that owners of geriatric horses ensure their horse has an annual health-check from the vet so these problems can be picked up earlier.”

Dr Pinchbeck said it would be useful to carry out further research into lameness in geriatric horses to find out the main causes of lameness and how these may be prevented or treated. There are many potential causes of lameness in horses, including arthritis, laminitis and foot problems.

The research team also found that half of the horses euthanized were suffering from concurrent health problems and these influenced the owner’s decision to euthanize in 43 percent of cases. The most frequently reported additional health problems were musculoskeletal problems, such as arthritis.

The mortality rate among the horses surveyed was 11 per 100 horse-years at risk, meaning that if 100 geriatric horses were followed for a year, an average of 11 would die. The mortality rate for horses over 30 years of age was over five times the rate than in horses aged 15 – 19 years.

Jeanette Allen, Chief Executive of The Horse Trust, said the data provided by this research is likely to provide useful information for both horse owners and veterinarians to enable them to improve the welfare of older horses.

“As there are a significant number of geriatric horses in the UK, it is vital that we understand more about the health problems that affect them,” said Allen. “We hope that more owners of older horses will give their horse an annual health-check to enable the horse to have a longer, healthier life.”

The research was published in the September 2011 issue of Preventive Veterinary Medicine.

The information in this article is edited from a report received from one of The Jurga Report’s favorite charities, The Horse Trust. Founded in 1886, and run for many years under the name “The Horse of Rest for Horses”,  it is the oldest horse charity in the UK and serves the horses of that nation in several ways. First, the Horse Trust still provides a place of retreat for working horses that have served their country or community and nurtures them throughout their final years. The charity also gives sanctuary to horses, ponies and donkeys that have suffered and need special treatment.

On another level the Horse Trust funds non-invasive research that advances knowledge of equine diseases, improving diagnosis and treatment and reducing suffering among equines worldwide. The charity also offers training for professionals and owners, with a focus on equine welfare and quality of life assessment.

The Horst Trust does good things for horses and deserves the support of all of us.



jumping-foal-713469 by Fran Jurga
© The Jurga Report at Equisearch.com 
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Equine Inflammation Research Scrutinizes Function of Two Peptides; Project Seeks Path to New Drugs, Fewer Side Effects

August 18, 2011

Horse Trust LogoA research project funded by Great Britain’s The Horse Trust has made important discoveries about how two peptides regulate the inflammatory response in horses. This knowledge could help with the development of improved anti-inflammatory drugs, which are used to treat a wide range of conditions in horses.

Inflammation is the body’s natural response to things that cause it harm.

However, sometimes the inflammatory response can be excessive, causing discomfort or pain and delaying recovery. Inflammation is associated with a wide range of equine diseases, including recurrent airway obstruction, laminitis and sweet itch. Although inflammation on its own is rarely life-threatening, if a horse has an inflammatory condition that cannot be managed, it may have to be euthanized.

Anti-inflammatory drugs, such as glucocorticosteroids, are regularly used in veterinary practice. These drugs mainly work by blocking the formation and/or actions of compounds produced in the horse’s body that cause inflammatory responses. However, these drugs are not always effective and can have unwanted side effects.

This research, funded by The Horse Trust, aimed to find out more about two naturally-occurring peptides (chains of amino acids that are shorter than proteins) known as annexin-1 and CXCL8. Both have been shown to affect the inflammatory response but little research has been done on their effects in horses. In the long term, knowing more about these compounds could help in the development of new anti-inflammatory drugs with fewer side effects.

During inflammation, neutrophils (a type of white blood cell) stick to the cells lining blood vessels and migrate into inflamed tissue, where they ingest and break down harmful agents. Using techniques that mimic these events, CXCL8 was found to cause adherence and migration of horse neutrophils. However, when it was used in combination with another pro-inflammatory substance, neutrophil migration and adherence were markedly decreased.  This suggests that attempts to reduce inflammation by blocking the actions of CXCL8 might not be as beneficial as had been thought.

At the start of the project, the researchers had no information about horse annexin-1, other than its gene sequence, so their first step was to develop a method to detect the peptide in white blood cells. They established that it was present and, as horse annexin-1 has not yet been synthesised, they used a synthetic peptide derived from annexin-1, Ac2-26, to look at the effects on horse neutrophils.

They found that Ac2-26 decreased neutrophil adherence and migration in response to other pro-inflammatory compounds, although at high concentrations the peptide itself caused some cell activation, thereby increasing inflammation. They also found that dexamethasone (a glucocorticosteroid) increased the levels of annexin-1 in cells, indicating that, as in humans, this class of drugs is likely to act in part through the formation of annexin-1.

These findings suggest that the use of compounds which mimic the actions of annexin-1 may have limitations as anti-inflammatory drugs. As glucocorticosteroids partly work by forming annexin-1, further research is needed in order to find out how annexin-1 will act in the horse’s body and establish how its formation contributes to the beneficial effects of these drugs.

The research project was led by Professor Fiona Cunningham at the Royal Veterinary College in Hertfordshire and Dr Karen Rickards at the Donkey Sanctuary in Sidmouth, assisted by Dr Andrew Brooks at the RVC, and by Dr Kirstie Pickles, now at the Royal (Dick) School of Veterinary Studies in Edinburgh.

“This Horse Trust-funded research has resulted in some very interesting findings about how inflammatory cells are regulated in horses” said Professor Fiona Cunningham. “The receptors that annexin-1 and CXCL8 act upon could be targets for new equine inflammatory drugs, but more research is needed first to fully understand their actions and how they produce these effects.”

The team’s research has been accepted for publication by the journal Veterinary Immunology & Immunopathology.



jumping-foal-713469 by Fran Jurga
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Periodontal Disease in Horses Linked to Gram-Negative Bacteria, Not Just Food Impaction, in Scottish Study

March 14, 2011

Smile

Equine dentistry is big business these days. The availability of precision power tools for dentistry has given veterinarians and equine dentists an upgrade to first class in the ability to identify problems that could adversely affect the teeth and a horse’s all-important ability to graze and chew its food.

It may be easier to see what’s wrong, and a power tool may be easier to wield than a tooth rasp, but it’s interesting to note that there are still big gaps in the scientific knowledge of the healthy equine mouth, as well as any abnormal conditions or diseases. Dr. Hilary Clayton’s research at the Michigan State University College of Veterinary Medicine’s McPhail Equine Performance Center is an example: she used video fluoroscopy to document how horses used different bits, where bits sit in the mouth and how horses swallowed with different bits. No one had ever documented that before. She asked us to consider what she called “oral conformation”–not all horses’ mouths were shaped the same, she warned, and not all horses would have similar responses to the same bit.

(Note: Dr. Clayton’s studies and comments on bits and the horse’s mouth can be found on the McPhail Equine Performance Center index of dressage-related research published in USDF Connection.)

Likewise, who really knows what happens when horses have dental problems and why one horse suffers when another merely needs occasional floating? Alistair Cox at the University of Edinburgh has completed the first study to describe the very basic microscopic anatomy of equine periodontal disease and the potential role of bacteria; his research was funded by The Horse Trust.

Equine Dentistry

Equine periodontal disease is a common condition in horses. According to a 1970 study by Baker and published in the Equine Veterinary Journal, it affects around 60 percent of British horses over the age of 15 years. The disease is painful and can have a big impact on a horse’s quality of life, affect the animal’s ability to eat and affects its performance.

Although bacteria are known to be a cause of periodontal disease in humans, cats and dogs, their significance in relation to the disease in horses is less clear. Mechanical factors, such as food being packed between the horse’s teeth due to abnormal growth and spaces, were considered to be the primary cause of the problem in horses.

For the research, Cox examined the skulls of 22 horses that had been submitted for post mortem examination. Although none of the horses had received treatment for periodontal disease, 16 had some form of periodontal disease.

cowboymouth

“This research, funded by The Horse Trust, highlights how common periodontal disease is in horses. Yet many horses don’t receive treatment so are likely to be suffering in silence. I would advise all horse owners to get their vet or equine dentist to regularly check their horse to see if it is developing the condition,” said Cox.

Cox identified bacteria, including spirochetes, that were associated with the presence of periodontal disease. Spirochetes are known to be important in human and canine periodontal disease, but this is the first study to identify spirochetes associated with equine periodontal disease.

Spirochetes are a type of anerobic, Gram-negative bacteria, so called because they have a spiral shape. They are implicated in several important disease processes.

Equine Dentistry

“This study shows that bacteria may be more important than was previously thought in the development of equine periodontal disease. More research is needed to understand whether bacteria or mechanical factors are the main cause of the disease. Once we have a better understanding of why and how the disease develops, we can do more to prevent horses from developing this painful condition,” said Cox.

The Horse Trust-funded research also found a significant association between the age of the horse and periodontal disease. Skulls were examined from horses ranging from 4 to over 20 years of age. The older horses were found to be more likely to have periodontal disease and a more advanced form of the condition.

Cox examined the skulls under the microscope and under x-ray. He found various histological features associated with equine periodontal disease, including hyperplasia, ulceration and neutrophilic inflammation of the gingival epithelium, mononuclear and eosinophilic inflammation of the gingival lamina propria, and mononuclear inflammation of the periodontal ligament.

Cox also found an association between equine periodontal disease and radiographic evidence of interdental bone lysis and diastemata, but this association was not statistically significant.

Read about the Horse Trust’s previous research on equine oral health on The Jurga Report.

Photos: Pony with charming underbite by Tim Zim; Inside of horse’s mouth by Nancy Sims;  John C. Froenig DVM of the Animal Medical Center in Hutchinson, MN working on mare with a motorized equine dental tool by Peter J. Markham, Loretto, MN. All hosted via Flickr.com.

Go to the main page of The Jurga Report to view more content.



jumping-foal-713469 by Fran Jurga
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Foal Immunodeficiency Syndrome Research Leads to DNA Test for Pony Foals

March 1, 2011
British pony, courtesey of Wellcome Trust

British pony breeds are benefiting from a new genetic test to identify carriers of Foal Immunodeficiency Syndrome (FIS), developed with funding from The Horse Trust. (Wellcome Library image)

Chalk one up for the little guys.

Equine research that is specific to ponies or pony breeds is not something that is in the news on a regular basis. In fact, quite a bit of equine research is conducted solely on horses, leaving pony breeders to assume that it is relevant and applicable to the smaller horses and ponies, who often carry a distinct genetic code.

So when research is conducted specifically for a problem found in ponies, it’s quite a red-letter day for our pony pals.  And when the testing is specific to a problem in breeds listed by the American Livestock Breeds Conservancy and the Rare Breeds Survival Trust in Great Britain, it’s obviously a day to remember.

A genetic test for carriers of Fell Pony Foal Syndrome, developed with funding from The Horse Trust, has been a hit with the Fell and Dales breeding community, with nearly 1000 breeders submitting samples for testing in just one year. Fell ponies are on the endangered list of rare breeds, and Dales pony are on the “watch” list.

Fell Pony Foal Syndrome, which is now known as Foal Immunodeficiency Syndrome (FIS) as it also affects other breeds of ponies, is an untreatable, fatal condition. Foals affected by FIS have severe progressive anemia and a deficient immune system, which leads them to succumb to infection. Foals with FIS usually die by the age of three months.

A three year research project, which was led by Dr June Swinburne at England’s Animal Health Trust in collaboration with Professor Stuart Carter of Liverpool University, identified the mutation that causes the disease and developed a genetic test to identify ponies carrying the mutation. As the disease only occurs in foals when two carriers are bred together, breeders can use the test to prevent the disease by ensuring that known carriers are not bred together.

Since the genetic test was launched in February 2010, Swinburne’s team has tested 970 samples from Fell and Dales ponies, of which three quarters were from Fell ponies. As there are around 8,000 Fell ponies worldwide and around 1,100 Dales ponies in the UK, this means that already nearly 10 percent of Fell ponies and over 20 percent of Dales ponies have been tested for FIS.

Among those tested, Swinburne found that 47 percent of Fell ponies and 10 percent of Dales ponies carry the mutation for FIS.

As well as testing carriers of the disease, the test also allows breeders to diagnose FIS in newborn foals. It can be difficult to make a clinical diagnosis of FIS, as foals often appear to be normal for the first couple of weeks and then start to show symptoms, such as diarrhea and pneumonia, which may or may not be linked to FIS. The test allows breeders to get a quick and definitive answer on whether a foal has FIS, allowing the foal to be euthanased before it suffers. Over the last year, Swinburne’s team diagnosed 13 foals (12 Fell ponies and 1 Dales pony) using the test.

“We are really excited that the research we’ve funded has had such a big impact on the welfare of Fell and Dales ponies. We hope that breeders will continue to make use of this test to ensure that no more ponies have to suffer needlessly from this distressing disease,” said Jeanette Allen, Chief Executive Officer of The Horse Trust.

The genetic test has also been used to investigate whether the FIS mutation has been passed to other pony breeds through inter-breeding with Fell or Dales ponies. PhD student Laura Fox-Clipsham tested 200 samples from each of the following breeds in Britain: Coloured, Welsh Section D, Highland, Clydesdale and Exmoor ponies. She found a low level of the mutation in the population of Coloured ponies, but did not find any evidence of the mutation in the other pony breeds.

The mutation that causes FIS was found to be caused by one base change in the DNA of chromosome 26 in horses. The genetic test for FIS requires a sample of hair from a pony. The DNA is extracted from the hair and the relevant section amplified using a technique called Polymerase Chain Reaction (PCR). The amplified DNA is then sequenced to see if it includes the mutation.

To learn more: Read an article about what was then called Fells Pony Syndrome in a 2008 article on The Jurga Report.



jumping-foal-713469 by Fran Jurga
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