Tuesday, August 17, 2010

Pathology of the Throat and HPV

It has been well documented that the human papillomavirus (HPV) can cause cervical cancer. There is now evidence that HPV main play a role in throat cancer. Does the unsafe sexual behavior presently done mean that there may be an epidemic of oropharyngeal cancer in the future? The or pharynx consists of the middle part of throat behind the mouth including the back one-third of the tongue, the soft palate, the side and back walls of the throat, and the tonsils. Cancer in this area can be difficult to diagnose and treat.
Maybe it’s time to treat this like cervical cancer. Pap smears on women at high risk of developing cervical cancer using Pap smears and HPV testing have helped to drastically reduce the death rate from cervical cancer in the industrialized world. Earlier detection has led to early treatment and better outcomes.
Would performing Pap smears on specimens from the oropharyngeal area be an effective screening test for throat cancer? Or what about gargling with mouth wash, and then centrfiuging the washings down to look for suspicious cells?
Hopefully, someone is reading this blog and it will get them asking the same question. Screening for an illness is the first step to treating an illness.

Tuesday, July 27, 2010

Explaing the 'e' in eGFR

What’s with this GFR test? For years there we were, medical professionals, just doing our jobs when out of nowhere comes a ‘new’ test we suddenly have to become knowledgeable of. It’s like we’re the only child whose parents have come home with a brand new baby sibling that we’re suddenly suppose to instantly love and accept. We didn’t ask for it, and things were fine until it came along to cause a lot of uncomfortable questions.
Hopefully this entry will answer questions about this newest diagnostic test.
First of all, GFR stands for Glomerular Filtration Rate. The glomerulus is the structure in the kidney responsible for filtering blood, so determine how well it is working can be used to measure kidney function.
Second of all, it’s not a new test. It’s actually a number calculated from a formula using four variables; plasma creatinine, age, gender and race.
Thirdly, the GFR derived from this formula is actually an estimated GFR . That’s why some labs report it as eGFR. Performing an actual GFR requires injecting a patient with a nuclear isotope (125I-iothalamate) and determining how long it takes for the kidneys to filter it out of the body. This is a procedure that cannot be performed on a large scale to screen patients who are at risk of developing chronic Kidney Disease (CKD).
In 1989 the National Institute of Diabetes and Digestion and Kidney Disease in the U.S. performed a study to see what affect diet could have on CKD and two of the tests used were plasma creatinine and 125I-iothalamate GFR.
As a result, a lot of useful data was produced, allowing researchers to develop a formula to quickly estimate GFR. The result was a magic number of 60 ml/minute/1.73 m^2. As long as the eGFR was 61 or greater, than the risk of CKD was decreased. A eGFR of 60 or less indicated further investigation.
Actually then, all the eGFR does is take the plasma creatinine and present is as a number to indicate kidney function.
But here are some ground rules for using the eGFR.
It cannot be used for paediatric patients eighteen years and under cannot have an eGFR performed on them. The test is gender specific. African Americans have a higher content of muscle, requiring a different formula than non African Americans.
Plasma creatinine must be used. Values from Point of care analyzers measuring creatinine using whole blood cannot use this formula.
In fact, any analyzer that measures plasma creatinine to calculate eGFR has to be standardized. What does that mean?
Finally, any analyzer that measures plasma creatinine has to be standardized. What does that mean?
The purpose of the eGFR is to screen patients at risk of developing CKD. However, if the analyzer being used has a high degree of variability , there is the potential for the patient having a wide range of results. One day your patient could have kidney disease with a eGFR of 58, the next day they could be a healthy 62.
An example of a successful standardization program is the one launched by the province of B.C. in 2003. It provided labs with specimens of known creatinine values for them to analyze. These labs then sent the results to the province, which calculated a correction factor for the analyzer.
The results speak for themselves.
Before the standardization program labs on average were reporting eGFR values 16.5% lower than they actually were. This meant that 535,000 British Columbians had been falsely diagnosed being at risk of developing kidney disease. By having labs use the correction factor in their formula for calculating eGFR, 449,000 patients were prevented from being misdiagnosed. Needless anxiety for the patient was avoided as well as the cost savings. The standardization program cost $335,000 to launch, and has a yearly budget of $135,000. Part of that goes towards educating physicians, patients and allied health professionals on the strengths and weaknesses of the eGFR as a diagnostic tool.
So the eGFR has become a useful diagnostic tool. The important thing is to be aware of its limitations, and not to obsess about its numbers.

Thursday, July 1, 2010

Genetic Strip Mining

My first lesson on neonatal screening made a dramatic impression on me. I was a student at BCIT in 1985 and it was during a lecture in clinical chemistry the PKU test was explained to me. Before this test had been developed, thousands of newborns each year were destined to be warehoused in state run facilities for the mentally impaired with no hope of any sort of normal life. The lecturer had worked in that time frame to see firsthand these patients.
So what happened to change this?
In 1934 Dr. Asbjorn Folling of Norway observed that certain mentally retarded patients smelt strange. Giving in to his curiosity, he discovered the source of the odour was phenylacetic acid present in the patient’s urine. From his observations, Folling concluded that the mental retardation resulted from genetics and diet. Since the source of the phenylacetic acid was from a chemical called phenylketone, and it was present in the urine, the disease was called phenylketonuria (PKU).
So the next step in treating the disease was to determine how this all caused mental retardation in what appeared to be healthy newborns. The answer was that these infants were lacking an enzyme called phenylalanine hydroxylase which breaks down an essential amino acid called phenylanine . Without this enzyme, there is a build up phenylanine levels in the blood, resulting in elevated levels of phenylanine which are harmful to the central nervous system and if left untreated, lead to brain damage. Unable to properly break down the phenylanine, it is then converted to phenylacetic acid, which is then excreted into the urine.
In 1951 Horst Bickel, a German professor, developed a protein drink without any phenylanine in it, allowing for a infant with PKU to receive proper nutrition. Then in 1958, Robert Guthrie developed a way for testing for PKU that was simple and inexpensive. All it involved was placing a few drops of blood on a piece of filter paper. Eight years later in 1966, hospitals began screening for PKU.
In 1986, that was a very powerful message. Laboratory technologists could improve a patient’s outcome with a very simple test. Families were spared the bitter burden of institutionalizing a child.
Since this first neonatal screening, other tests have been included, such as genetic screening for cystic fibrosis and sickle cell anemia.
Unfortunately now events have occurred that have challenged just not PKU testing be done, but all neonatal screening.
In the four decades since the first PKU screening, genetic testing has grown exponentially. A person’s entire genome can be determined from a single drop of blood. Parents are concerned that blood stored on a PKU card can be used to determine that child’s genetic information, and be kept in a private data base. There is an expectation of privacy that blood samples from the millions of PKU cards collected is not turned into some huge ‘genetic strip mine,’ as researchers and private companies take advantage of this huge pool of DNA.
Parents cannot let fear prevent them from having their infants screened for disease. At the same time researcher’s have to be allowed to do research at a molecular level to help with disease diagnosis and treatment. The millions of PKU cards stored in hospitals world wide make a tempting target.
It is for the good of the newborn that government makes newborn screening mandatory, and it is also good that researchers try to find a treatments and cures for disease. In a historical perspective, did the doctor mentioned earlier, Dr. Folling, have to get permission to begin those groundbreaking experiments that led to the discovery of PKU? What if he had been denied that opportunity to find out why those patients had strange smelling urine, how many millions of patients would have had negative outcomes?
True, there has to be a limit to who has access to stored genetic material, whether it be dried blood on filter paper to tissue biopsies from a cancer patient. It is time for politicians to become not only involved, but informed.
What would my solution be? Earlier I used the term ‘genetic strip mining.’ Treat all stored genetic material as a public resource, and any company that develops that resource pay a royalty to the government for that material. Respect of patient’s privacy is paramount
These are interesting times. But we can’t let fear prevent us from making sure children of every generation have a chance to overcome the challenges they face in this business we call life, including the DNA they are born with.


Friday, April 16, 2010

A giant step for medicine

One day future medical laboratory technologists will thank Barak Obama for setting in motion a manned space mission to Mars.
Why?
Because the last time man stepped on another celestial body (the moon), the payoffs for laboratory medicine were many. By pushing for the miniaturization of electrical components such as transistors, medical laboratory science was able to transfer the technolgy to developing analzyers that were becoming more and more sophisticated. The technology has also helped develop CAT and MRI scans as well.
Without doubt, there will be challenges. But the knowledge gained from overcoming these obstacles will have long term positive outcomes for medicine. Who knows what new technolgies and advancement will be developed (don't be surprised to see fantastic developments in nanotechnolgy).
Maybe they will even develop that holy grail of science fiction, the tricorder.

Sunday, January 10, 2010

Platelet Rich Plasma

In honour of the Olympics this blog will be dedicated to the topic of Platelet Rich Plasma (PRP). Lately PRP has been getting much media attention as a new miracle cure for athletic injuries. So what exactly is PRP, and how does it work?
If you were to take a tube of unclotted blood and spin it in a centrifuge, it would separate into two portions, a liquid portion called plasma, and a solid portion made up of cellular elements. The cellular portion would be divided into three categories. The largest portion would be the Red Blood Cells (RBC), responsible for carrying oxygen to the tissues. The next portion would be the White Blood Cells (WBC), the cells responsible for the body’s immune system. The final type of cells found would be the platelets, the cells responsible for blood clotting.
It is because of this function that platelets have been getting a lot of bad press lately. After all, circulatory disease is the major killer in the industrialized world, all caused by the blood flow to tissue interrupted by the formation of platelet clotting. A lot of treatment such as aspirin and plavix, is based on reducing the clotting activity of platelets, so why would someone want to inject plasma that has an increased concentration of platelets?
Because despite the fact that platelet clumping can lead to death, platelets do more than stop blood flow when they are activated.
After all, without platelets we would all die from bleeding to death. When tissue is damaged, it releases chemicals that activate platelets to clump and form a plug to prevent blood from leaking out. Once activated, platelets will also release chemicals from granules inside of them. These chemicals help the body to start repair the damage to the tissue.
Two of the most important activators are Platelet Derived Growth Factor (PDGF) and Transforming Growth Factor Beta (TGF-β). PDGF attracts WBC, fibroblasts and smooth muscle cells to the injury site. Once there these cells begin tissue repair by the formation of new cells, capillary networks that increase blood flow to the damaged tissue and fibronectin, a cellular super glue that holds all of this together. TGF-β also attracts cells to the damaged tissue and also causes cells to increase production of collagen and fibronectin.
In 1986 researchers l decided to see if platelets could be used to heal tissue. By centrifuging blood at a certain speed, WBC and RBC’s will sink to the bottom, while leaving platelets to float in the plasma at increased levels. The plasma, now rich with platelets is then removed. By adding chemicals to activate the platelets to begin clotting, a gel forms that can be applied to wounded tissue to speed up repair. This has been used successfully in different types of surgery to speed up recovery.
Recently though, doctors in sports medicine have decided trying injecting the PRP straight into the damaged area, usually a soft tissue injury such as Achilles tendonitis. Many famous athletes have received this type of treatment with resounding success.
Recent studies have shown this to be due mostly to a placebo effect. Researchers injected patients with either saline or PRP, and received the same results. Their conclusion was that using PRP for soft tissue injury caused by a sports injury was useless.
However using PRP by activating the platelets to form a gel has been found to help patients recover from surgery or unhealed ulcers.