Category Archives: Diagnostics

Cross-continental collaboration from farm to fork

dFood sustains us but also can endanger us. In the first major public health project between Cornell’s College of Veterinary Medicine and Weill Cornell Medical College-Qatar, a team of multidisciplinary cross-continental collaborators aims to mitigate food contamination and keep food clean, from production to consumption, in Qatar.

With a $1 million grant from the Qatar Research Foundation, Hussni Mohammed, professor of epidemiology at the Veterinary College, is leading a project to assess risks associated with food-poisoning pathogens. Drawing from a network of faculty and resources spanning the two campuses, Mohammed’s team will carry out risk assessment studies to model how pathogens put the public at risk in order to better inform efforts to control contamination.

“We are investigating the epidemiology and ecology of food-borne pathogens as they move through the food chain from the sources to the table in Qatar,” said Mohammed. “Four kinds of bacteria pose major threats to Qatar’s food systems: Escherichia coli, Salmonella, Campylobacter and Listeria monocytogenes. We aim to determine each species’ prevalence; to identify agent, host and environmental factors that perpetuate these pathogens; and to ascertain factors such as antibiotic resistance that could contribute to development of new virulent strains.”

fThis research will help answer questions crucial to addressing contamination. Does infected milk come from infected cows? Or are pathogens more likely to enter the food chain in the packaging facility, during transportation or at the retailers where milk is ultimately sold?

Following food from farm to table, Mohammed’s team investigates all levels of the supply chain, drawing samples from food animals, their products, the environments they pass through and the humans consuming them. Using bacteriological and PCR techniques to test for pathogens at each level, Mohammed is constructing data-driven mathematical models to determine where and how these pathogens infiltrate the food supply system.

“The models we develop will help producers and public agencies develop and implement cost-effective and science-based strategies to ensure the safety and sustainability of Qatar’s food supply system,” said Mohammed. “Taking our data a step further, we are using the samples from humans to search for ties between food-poisoning pathogens and inflammatory bowel disease (IBD). Little is known about IBD, but several studies suggest it is caused by bacterial imbalances in the gut. We hope our data can help elucidate correlations between these food-borne pathogens and IBD.”

He added: “Qatar is a quickly developing country committed to supporting new research through the Qatar Foundation. It is a privilege to be involved with a project in Qatar that could have life-changing applications for public health in the region and in the wider world.”

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Dissolving diseases

International dog disease expert eliminated ailments across species and the world

“I started at James Baker’s lab under a challenge,” said Leland ‘Skip’ Carmichael, PhD ’56. “I came in his office looking for graduate work. He told me I had six months to figure out how a dog’s immune system responds to canine hepatitis, or I was out.”

Fortunately for dogs across the world, Carmichael passed the test. Over the 40 years he spent at Baker Institute he became one of the world’s best-known international authorities on canine infectious diseases. He has characterized, developed tests and treatment plans for, and invented vaccines against most major canine infectious and reproductive diseases, including distemper, hepatitis, canine parvovirus-2, canine herpesvirus, and canine brucellosis.

“We were at a time when diseases were being recognized and their causes clarified,” said Carmichael. “We focused on research that could directly benefit animals, and always saw our problems in the field.”

From the field to the lab, Carmichael exercised an aptitude for innovation in eradicating disease. “Baker Institute was one of the first labs to use tissue culture methods to isolate viruses, look for vaccines, develop serological tests, and measure immune responses,” said Carmichael. “When a mysterious disease began causing widespread abortions in dogs across the nation, I was charged with figuring out why. By air delivery at midnight I received a paint can that contained aborted fetuses and placental tissue. I went straight to the lab and inoculated plates with tissue samples.  The next morning the plates had bloomed with bacteria I’d never seen before.”

Carmichael had found a new species of Brucella, bacteria causing a devastating venereal disease best known for killing farm animals and harming humans who consume infected raw milk.

“Brucellosis is one of the most important veterinary diseases. We were the first to recognize the canine strain and establish control. We offered a free testing service, and fielded over 10,000 phone calls in the first year. Now Cornell’s Animal Health and Diagnostic Center runs the most reliably accurate Brucellosis test I know. The disease has all but disappeared in dogs.”

Today, canine infectious diseases are much rarer than when Carmichael first stepped into Baker’s office, in part because of the work he and his colleagues at Baker Institute have done. Meanwhile, his educational legacy continues. Carmichael’s former graduate student Collin Parish now directs Baker Institute.

“Dogs are part of the human experience,” said Carmichael, “but we’ve seen a nation-wide diminution of canine research in recent years. Most funding comes from institutions that favor research modeling human disease. Baker believed that veterinary research should focus on diseases of animals, I was fortunate to work in a time when that goal garnered strong support. I hope this institute will continue conducting research that can help dogs in the future.”

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‘Scopes Magazine
July 2011

Clinical pathology resident receives grant to study blood clotting

vClinical Pathology resident Dr. Nora Springer received a $2500 research award from the American Society for Veterinary Clinical Pathology (ASVCP) in March 2011. For the past three years, ASVCP has given one “Share the Future” research award per year, based on the quality of the candidate’s written proposal and the potential of the project to expand the knowledge base in veterinary clinical pathology. The grants range from $1,000 to $2,500, and are used to support new research by clinical pathology residents and graduate students.

Springer will use her award to investigate how tiny particles shed from platelets in the blood can lead to blood clots and thrombotic diseases in horses. She hopes to develop tests that will detect developing problems and help prevent thrombosis. Every cell in the body sheds microparticles, and those derived from platelets are the most common kind in the blood. These platelet-derived microparticles encourage blood to coagulate, and if enough accumulate they can form clots in blood vessels that obstruct blood flow, leading to thrombotic diseases in both horses and humans.

“Horses are at risk for thrombosis with inflammatory diseases, some of which are quite common, such as colic. The onset of thrombosis can drastically alter the clinical course of the disease and result in longer hospitalization times or death,” said Springer. “Unfortunately, Thrombosis is difficult to prevent because current tests can’t detect when a patient is at risk. Identifying at-risk patients before symptoms emerge is essential to guide therapy and minimize these diseases. I aim to develop new testing methods using bead-based flow cytometry that will count platelet-derived microparticles in equine blood and plasma, and to determine how these microparticles influence thrombosis.”

These new tests may allow clinicians to detect and predict thrombosis in patients, and develop treatments or prevention plans to stop the onset of blood-clotting disease.

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http://www.vet.cornell.edu/news/Springer.cfm

Training future leaders in diagnostics

Graduation rarely means the end of education, especially in the medical world. A veterinary degree opens doors to countless further training opportunities. The College of Veterinary Medicine and the AHDC offer residency programs that let DVMs delve into in the cellular side of disease. In the residencies for Diagnostic Sciences and Clinical Pathology, veterinarians wanting to gain more experience in diagnostics come to Cornell to practice for three years under the mentorship of seasoned specialists before testing to become board-certified specialists themselves.

Residency in Diagnostic Sciences

Wonhee Cha pioneers the nation’s first veterinary residency program in diagnostic sciences here at the AHDC. With a collection of experience in international clinical service and epidemiology research under her belt, she is honing her diagnostic tools in preparation for a future foray facing infectious diseases of the third world.

After earning her DVM from Kon-kuk University in Korea, Cha volunteered in Tanzania for two years as a public veterinarian. “The entire country has just one veterinary school and about 250 registered veterinarians,” says Cha. “Everywhere I turned, people and their animals needed help. One day I would be stitching up dogs or helping breed livestock, the next I would be educating farmers about husbandry techniques, or working on my biggest project establishing Tanzania’s first x-ray-capable veterinary center.”

Cha’s commitment to international veterinary fieldwork blossomed during her tenure in Tanzania. “When I visited villages to vaccinate chickens against New Castle Virus, I began to see just how vital their animals’ health was to their livelihood. People relied on their chickens for eggs, meat, and trade. Any infectious outbreak could be devastating.”

When the service period ended, Cha went on to pursue her burgeoning interest in epidemiology at the laboratory of infectious diseases and molecular biology at Ohio State University, where she earned her master’s degree.

“I was studying ways of detecting and differentiating types of the Avian Influenza virus,” says Cha, “and I began to realize how important it is to have good diagnostic tools. Without accurate diagnostics, you can never hope to study any epidemic. I wanted to learn these tools in a clinical setting.”

So Cha came to the College of Veterinary Medicine in 2008 to learn the diagnostic tools she needed, and to apply them to hands-on disease research at the College’s integrated hospital and diagnostic lab. As the solitary inaugural resident in the country’s first diagnostic sciences residency program, Cha is paving the way for the future of the field.

“We need more people who can do veterinary diagnostic work,” says Dr. Craig Altier, microbiologist at the AHDC and supervisor of the innovative position. “Most of us got our experience on the job. We were starting to worry about what will happen as we grow older. There are very few diagnostics training programs and it’s hard for a young person to get involved. So we worked to develop this new kind of residency.”

While other diagnostic residencies focus on a single area from the start, residents in this program spend the first year rotating through each of the AHDC’s thirteen sections, gaining an understanding of each diagnostic area and a comprehensive look at the field as a whole. In her first year Cha spent time in each section, including anatomical pathology, avian disease, bacteriology, clinical pathology, comparative coagulation, serology and immunology, endocrinology, molecular diagnostics, parasitology, quality milk production services, toxicology, virology, and veterinary support services.

“This is the only program that gives such an expansive overview, and that allows veterinarians to choose between different diagnostic specialties,” says Altier. “We want to train students who will become leaders in the field, with a broad enough scope that they could one day actually run a diagnostic laboratory.”

Following a year of rotations, Cha settled into the section of bacteriology, where she does a combination of fieldwork and research studying bacteria in dairy cattle of the New York State watershed. “Everyone is my teacher,” says Cha. “I’m surrounded by a wealth of knowledge and experience, from the technicians to the faculty, everyone has so much to teach. I feel humbler every day.”

In her third and final year, Cha continues her work in bacteriology, hoping to finish her PhD before setting out to pursue her dream of addressing infectious diseases of animals in developing countries.

Residency Program in Clinical Pathology

Sometimes you can look at an animal and know what’s wrong, but many mysteries of disease lurk far beneath the surface, in the cells themselves.

Clinical pathology residents Drs. Nora Springer and Erika Gruber ’06 are scientific sleuths who traded magnifying glasses for microscopes, investigating samples on the biochemical and cellular levels to study and diagnose disease.

“We deal with swabs, smears, and samples from almost any fluid or part of the body,” says Springer, who spent several years testing samples as a licensed veterinary technician before earning her DVM at Kansas State in 2008 followed by a small-animal internship at Louisiana State University. “This includes blood, urine, bone marrow, tumor cells, anything that could give cellular or chemical clues.”

Clues can come from all kinds of cells, and part of a clinical pathologist’s job is to recognize what is normal and what is not from each sort of sample. When a sample comes in, the clinical pathology residents provide the front line of investigation. After inspecting, describing, and forming a diagnosis, they consult with the lab’s board-certified pathologists, Drs. Tracy Stokol, Heather Priest, and Deanna Schaefer, who look over the report and discuss it with the residents.

Unlike most pathology programs, the discussion doesn’t stop there. Cornell’s program encourages collaboration, and all five staff dedicated to clinical pathology pool their perspectives three times a week.

“I chose Cornell because of the program’s strong structure and unique team-oriented approach,” says Springer, who is in her second year of the three-year residency. “This is the only program I’ve found where residents and clinical pathologists regularly meet to discuss cases as a group. Most programs have each resident meet with one mentor. At Cornell two residents and three clinical pathologists all meet together to review cases, investigate archived slides, or practice describing and diagnosing ‘mystery slides’ with interesting quirks we can learn from. It gives us a very well-rounded experience.”

“You gain a lot by hearing different opinions from people trained in different environments,” says Stokol, one of the three clinical pathologists who supervise the program. “Our residents must do a rotation in anatomic pathology, and can also choose to rotate through other specialties, including oncology, toxicology, and large or small animal medicine. That’s been very helpful for them.”Clinical pathology residents divide time between clinical service and research, exposing them to both sides of the field.

“Cornell has a rich history and philosophy regarding research,” says Stokol. “We expect our residents to complete a research project. We want to invest in them the intellectual curiosity of asking ‘why is this happening’ and ‘how can I test that?’ Residents challenging you is part of the fun. It makes you think about what you know. Is it based on true evidence or is it just something your teacher told you? It’s good to challenge the status quo, that’s how you learn new things.”

“This program drew me because it’s so well-rounded, emphasizing the diagnostic aspects of both research and clinical work,” says Gruber, a first-year resident and Cornell alum who returned after a small-animal internship at Colorado State followed by three years of veterinary relief work. “Residents also take an active teaching role, which I particularly enjoy. We help with labs in blocks, give special lectures, and guide students through their pathology rotations.”

At the end of their three years of service, Gruber and Springer will apply their knowledge in a three-day examination for board certification in clinical pathology. Several career paths branch out for a newly ordained clinical pathologist.  Some go on in academia, pursuing PhDs and becoming tenure-track research professors or joining a clinical track emphasizing teaching and service. Others go into diagnostic practice in labs like the AHDC, or into private industry, particularly in the field of pharmaceuticals. The government offers further jobs for trained clinical pathologists.

“We need people who can spread their knowledge and educate the next generation,” says Stokol. “We need future professionals who can encourage young people like Nora and Erika to go on in clinical pathology. The ultimate goal of academics is training our replacements. This is a challenging and rewarding field, and it’s a pleasure to work with people who share your passion.”

Learning genes to label germs

Genetic comparison can identify mystery pathogens

Organisms from all corners of the animal world arrive at the doors of the New York State Veterinary Diagnostic Laboratory and Animal Health Diagnostic Center (AHDC). Foreign or familiar, prevalent or peculiar, pathogens must reveal their true identities before veterinarians can begin to make sense of samples, diagnose diseases, and develop treatment plans.

How do you identify a microscopic organism? The traditional method has guided doctors and scientists through the past 100 years. Smear a sample on an agar plate, a petri dish covered with gelatin made from seaweed, and study the culture as it grows. What shape does it take? Does it move or stay still? What is its biochemical profile? What food does it prefer? Scientists use these kinds of questions to match mystery organisms to those successfully identified in the past.

But sometimes matching lists of characteristics isn’t enough.

“We deal with some oddball organisms,” says Dr. Craig Altier, a microbiologist with big aspirations for the future of identifying small life-forms.  While traditional methods of identification can reliably distinguish common or easily differentiated organisms, they shed less light on outliers, including newly mutated species, rare breeds of bacteria, and fraudulent fungi.

“Fungi look very similar under a microscope, and often biochemical differences between species prove undetectable,” says Altier. “We really needed a better way to tell such species apart. So when physical characteristics failed, we turned to genetics.”

Every individual has a unique DNA fingerprint, and so does every species. Evolution shakes the genetic dice many times over, but all species have certain genes that survive unchanged for generations.

“These highly conserved genes usually code for essential functional elements that would not work if they were changed, such as proteins required for basic cellular function,” says Altier. “They don’t vary much between individuals, but they do vary across species. We can use these genes to accurately identify organisms.”

Researchers have already been looking at conserved genes to map out relationships between species, and now Altier and his colleagues are adapting these techniques for veterinary medicine.

“We have finally reached a point where we can use these tools quickly and efficiently enough to diagnose disease,” says Altier. “Human medicine will benefit as well, but the technique is most valuable in veterinary medicine because there are so many different species of host animals and pathogens.”

The new approach uses PCR techniques to amplify DNA from selected conserved genes. Cornell’s on-campus DNA Sequencing Center decodes samples into a string of about 500 bases of A, T, C, or G, then compares them to samples in the National Center for Biotechnology Information’s genetic database to look for similarities.

The technique is already revolutionizing diagnostics, revealing relationships that could never have been found before. “One day we received a swab from the flipper of a sick sea lion,” says Altier. “We had no idea what kind of organisms might live there, but we found the answer quickly through DNA sequencing and a quick genetic comparison. We couldn’t have done that without this database.”

Genetic comparison tools raise the bar for diagnostic accuracy. “With the old methods we frequently got stuck saying one organism is ‘like’ another,” says Altier. “Now we can usually hone in on a more exact label. We match sequences down to the letter to find efficient, accurate diagnoses.”

Comparative genetics can also expand our knowledge of a given disease.

“We may find the same kinds of pathogens in different animals we never knew could host them, or on the same host species but at a different body site,” says Altier. “These techniques have already shed new light on how organisms evolve and how different species are related. We may soon begin discovering new important pathogens previously left unnoticed.”

Even unidentified organisms could prove priceless down the road. Many currently unidentified sequences float nameless through the database waiting to be compared. “When enough of these orphans begin to match,” says Altier, “we will begin to discover new disease-causing agents.”

Looking through the window

Clinical pathology bridges animals and answers

 “Blood is the window to the body,” says Dr. Tracy Stokol, a professor with a passion for pathology puzzles. Microscopic magnification opens that window, revealing a cellular world which veterinarians explore in the quest to analyze disease. Clinical pathologists like Stokol navigate that world as diagnostic detectives, using cellular samples from body tissue and fluids to piece together a patient’s story.

If an animal has a bodily bump, how do you tell if it’s a bruise or inflammation, a fatty tumor or malignant cancer? Veterinarians use needles to take samples for examination. Clinical pathologists use these cellular clues to solve medical mysteries.

“It’s critical for veterinarians to know clinical pathology because they use it every single day,” says Stokol. “Sick animals can’t tell you what’s wrong. Samples speak for the animals and clinical pathology translates. It’s a bridge between the animal and the answer.”

Body fluids can reveal much of what goes on inside an animal’s body. “Blood can tell you why a joint is swelling, expose cancer cells, or show abnormalities that indicate underlying liver disease,” illustrates Stokol. “We also work with bone marrow aspirates, samples from lymph nodes, cerebrospinal fluids, anything you can put a needle into and take a sample of could give an important clue.”

Stokol has taught the visual language of cellular samples at the College of Veterinary Medicine since 1993, and is now an associate professor in the Department of Population Medicine and Diagnostic Sciences. A skilled specialist, Stokol attributes her passion for clinical pathology to the fun of solving a mystery.

“I like a challenge,” says Stokol with steady eyes that have faced plenty of challenge in the microscopic realm. “I’m always intrigued by difficult cases and love figuring things out. Clinical pathology is a very visual field. You’re seeing interesting changes that are visually fascinating. It’s fun to look at things, but it’s also about putting pieces of information together to make a story.”

Stokol’s story started in Melbourne, Australia, where she earned her veterinary degree in 1987, worked for two years as an assistant veterinarian, and earned a PhD before coming to Cornell. She belongs to several societies for clinical pathology, chemistry, and diagnostics, and has published several book chapters and over 50 papers in peer-reviewed journals, reflecting her dedication to furthering research in her field.

“Research stimulates a kind of intellectualism you don’t get from puzzling out a case. It’s an entirely different way of thinking,” explains Stokol. “A lot of what we do in clinical work is memorizing facts and recognizing patterns. Research lets you ask more kinds of questions, it makes you think ahead and plan, and learn to deal with things that don’t work out the first time.”

That’s why Stokol and her colleagues require that the College’s clinical pathology residents complete a research project.

“Working in an academic environment, we need to advance the knowledge of our field. We have to continue to grow and understand more about the diseases we’re working with and the only way to do that is through research.”

As an academic clinician, Stokol furthers her passion through her teaching. Together with fellow clinical pathologists Dr. Heather Priest and Dr. Diana Schaefer, Stokol supervises the College’s residency program in clinical pathology.

“We need academic clinical pathologists to keep advancing the field and to keep it alive. Fewer people go into clinical pathology because there are fewer residencies available. We’re graduating fewer people, so fewer people are trained.”

Specialists in this field need thorough training to learn to successfully sort out the secrets cells can tell. But for Stokol and her peers, the challenge is worth it.

“One of the job’s biggest appeals is the instant gratification, knowing that you’re making a difference,” Stokol says. “Clinical pathology gets rapid results that help animals and their owners almost immediately. You’re giving vital information that a veterinarian can use to decide how to manage or treat a patient, or helping an owner make a decision about whether to continue a treatment. We can make a diagnosis and know we’re having a real effect.”

“I like that I can do everything with clinical pathology at Cornell,” says Stokol. “Service helps patients in real-time, research expands our knowledge, teaching ensures the future. It’s the best of all worlds.”