Thursday, December 11, 2014

Ebola Virus

Although the Ebola epidemic isn't in the forefront of the news in the United States, its still a significant issue in west Africa. In Guinea, Liberia, and Sierra Leone, there have been 20,416 cases and 8,004 deaths (as of December 31, 2014 as reported at the CDC website) since the epidemic began in March. Only one African country was able to control the Ebola outbreak and as of October 19, 2014, Nigeria has been declared free of Ebola.

Many people, and even may scientists, do not know much about Ebola virus, nor how it causes disease. It causes the deadly disease hemorrhagic fever and mortality rates can be as high as 90%. As such, a biosafety level 4 (BSL-4) facility is needed to study the intact infectious virus. There aren't many of these labs and it requires much equipment and training to be able to work in these labs:

Scientists in a BSL-4 facility at US Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Md. Photo from:

The first known outbreak of Ebola occurred in 1976 in northern Zaire, now known as the Democratic Republic of the Congo. Since then there have been sporadic outbreaks with the current epidemic being the worst. Ebola is a zoonotic disease as it enters a human population from an infected animal. It is still not known which animal species (the reservoir) contains the virus for spread to other animals and humans but studies indicate that it is likely a species of bat.

Ebola virus is a member of the Filoviridae family of viruses. Filoviruses have an RNA genome, a helical capsid, and a lipid envelope with glycoprotein spikes. Viruses in this family include the Ebola virus, Marburg virus, and the recently identified Cueva virus. Ebola and Marburg viruses cause hemorrhagic fever. The Cueva virus was recently identified in bats in a cave in Spain and has not been shown to infect humans.There are five species of Ebola virus, three of which cause disease in humans: Zaire, Sudan, and Bundibugyo viruses. The Zaire Ebola virus is the one that is causing the current epidemic. Reston Ebola virus infects primates and pigs in the Philippines and does not cause disease in human.

Ebola virus virion. From

The Ebola virus genome has seven different genes which code for proteins that allow the virus to attach to and enter cells, replicate the virus chromosome, make more viruses, and cause disease. Some of these proteins pull double duty: they are needed for replication of the virus but they are also involved in the viruses ability to cause disease. These multi-tasking virus proteins are glycoprotein (gp), VP24, and VP35.

Ebola virus genome. From:

As with all viruses, Ebola virus needs to be able to enter cells and take over the cell to be able to make more viruses. The viral glycoprotein binds to a specific cell surface protein (the receptor) and gets the viral nucleocapsid (the protein coat & viral genome) into the cell to begin the replication cycle. The Ebola virus genome is a negative-sense RNA genome. What this means is that it can't be used immediately to direct synthesis of viral proteins. The genome needs to first be copied to a positive-sense RNA. When Ebola virus enters cells it brings with it extra proteins needed for this first copying step - L (viral RNA polymerase), VP30, and VP35. Once a positive-sense RNA is made, the cell's ribosomes will then translate that RNA to make all of the viral proteins. The L/VP30/VP35 complex will also copy the positive-sense RNA to make many copies of the virus chromosome. The various proteins that make up new Ebola viruses will then assemble with the negative-sense RNA copies to make nucleocapsids inside the cell. Ebola virus acquires its lipid envelope from the plasma membrane of infected cells via a process known as budding. The viral glycoproteins are incorporated into the plasma membrane during synthesis, VP40 and VP24 attach to the glycoproteins, then the nucleocapsid with VP35 and L attach to VP40 initiating a process by which the virus forces itself out of the cell (budding).

Ebola virus life cycle. From:

The goal for a virus is to make more viruses and get to the next host. To be able to do this, a virus will often express proteins that counteract the immune response. The goal of the host's immune response is to stop viruses from replicating and to get rid of the viruses already made. As a result, many symptoms, especially early symptoms of hemorrhagic fever, are actually your body's way of trying to get rid of viruses  (or anything foreign entering your body). So in essence, a virus infection is an arms race and a detente is reached - the virus wins by spreading to other people and you usually don't get killed - which is why vaccination is important (get your vaccines!). Three Ebola virus proteins have been shown to upset this arms race: glycoprotein (GP), VP35, and VP24. So how do these three viral proteins affect the immune response?

There are actually three forms of glycoprotein that are expressed. Some of these are due to RNA editing whereby extra adenines are added during copying of the negative-sense RNA and some are due to processing of the expressed glycoprotein. These three glycoproteins (GP) are the full-length glycoprotein that becomes part of the virus, a small secreted GP (ssGP)  and a secreted GP (sGP) that forms a dimer. sGP acts as a decoy antigen (an antigen is something that is specifically recognized by cells and proteins of the immune system). It will bind to antibodies that are directed against GP preventing those antibodies from binding GP and preventing virus infection, which means the antibody response against Ebola will not be as effective resulting in more virus infection. sGP is also expressed in much higher quantities than GP; therefore, more B cells are activated and more antibodies produced against sGP than against GP. This is called antigen subversion as the specific immune response against the virus ends up being weaker than it should. Again, the result is that more virus will be able to infect cells and produce even more viruses.

VP35 and VP24 both target what is known as the interferon pathway. Interferons (IFN) are a group of proteins whose function is to activate an anti-viral response in cells. IFN acts as a warning signal for uninfected cells. When a cell becomes infected with a virus, the cell responds by producing IFN, which is then released from the cell. IFN then binds to uninfected cells and activates an anti-viral response in uninfected cells so that cell will be primed to fight off the virus if the virus happens to get into the cell. Many viruses have evolved ways to stop this process so that more viruses can be produced.

One of the activators of the IFN response is double-stranded RNA, which is produced when the Ebola virus L/VP30/VP35 protein complex makes copies of the RNA genome. The cell expresses proteins, RIG-1/MDA-5, that bind to double-stranded RNA to activate the IFN response. VP35 of Ebola virus also binds to double-stranded RNA preventing RIG-1/MDA-5 from binding. Not all the double-stranded RNA will get bound by VP35 so the IFN response may still proceed. VP35 can also bind to proteins that are down-stream of the pathway (IRF-3/IRF-7) preventing these proteins from becoming activated. The end result is that very little to no IFN will be produced in cells in which VP35 is expressed.

Some IFN is produced in cells in response to Ebola virus infection, which will activate the anti-viral response in other cells. In these cells that are then infected by Ebola virus, VP24 will block activation of the anti-viral response. Upon binding of IFN to a cell surface receptor, STAT1, a transcription factor, becomes activated. It is transported to the nucleus via a carrier protein called karyopherin a1 to turn on genes needed for the anti-viral response. VP24 binds to karyopherin a1 to prevent it from bringing STAT1 into the nucleus, which means that the cell will be less effective at stopping virus infection. VP24 also binds to STAT1 directly but the effects of this are not currently known. The end result is more viruses being produced!

Ebola VP24 & VP35 inhibits IFN pathway. From:APP Zhang et al. Virulence 5:440, 2012.
Many of these proteins also have other effects on the tissues and organs of someone who is infected with Ebola virus resulting in many of the symptoms of hemorrhagic fever. Initial symptoms include: high fever, fatigue, dizziness, muscle, bone or joint aches, and weakness (similar to many other viral infections). As the disease progresses, bleeding may occur as well as some of the following symptoms: shock, nervous system malfunctions, coma, delirium, kidney failure, and liver failure. The hemorrhagic manifestations are a maculopapular rash (flat, red area on the skin that is covered with small confluent bumps) and mucosal bleeding (especially in the gastrointestinal tract).

On-Line Resources:
PLOS Ebola Collection:
UC Santa Cruz Ebola Genome Portal:
Science special collection:
Centers for Disease Control and Prevention:

Sunday, August 31, 2014

How to Write a Research Paper.

So you have to write a research paper for the science class that you had to take. Now what!?

First, what is a research paper? A research paper is a way of synthesizing information about a topic from a variety of sources in a coherent fashion. You will want to have enough information written in an organized manner to demonstrate to your professor that you learned something about the topic. You will want the paper to be well written and organized so you get a good grade and you don't bore your professor (this may not seem important but remember that she will be determining your grade and may have a lot of papers to grade. So make the paper stand out in a good way!)

1. Pick a topic that's interesting to you. Sometimes your professor will give you a list of topics; other times you will be given some general guidelines and have to come up with your own topic. Since you will be spending a fair amount of time doing research and writing for this assignment you should find something that may be of interest to you. Many students have no clue what to write about. You could start with your text book and see what jumps out at you. Perhaps you have a family member that was recently diagnosed with a disease that you could learn more about. Or you can look over the short articles at ScienceDaily where recent research papers are summarized.

2. Make sure the topic is appropriate to the assignment. Your topic should be within the parameters of what your professor wants. Read the instructions (you will see this statement many times because far too many students fail this part of the assignment!) or check with your professor. Listen to what she says during class about the requirements of the paper and write it down! You will want to make sure that your topic is not too broad so that you can include details and real information in your paper. Glossing over topics and writing a superficial paper will make it a boring paper for your professor to read and will likely result in you earning fewer points.

3. Use appropriate sources for the information for your paper. There is a lot of information on the web that can be used to write a research paper. Many of it will not be appropriate, some will. Your search for information should always begin at the library. Your library will have subscribed to a variety of databases that can be searched. Think of databases as a smaller version of Google. The database will be a collection of research papers or books that can be searched. Searching databases is more focused than doing a Google search. Google should not be your main way of looking for information for your research paper!

Some good sources of information:
  - an encyclopedia. Some good ones are Encylopedia Britannica, Tree of Life
  - articles in Scientific American
  - books
  - review articles in scientific journals. These have summarized the research results from a large number of labs. They are written for other scientists but many non-scientists should be able to read and understand it.
   - research papers in scientific journals.
   - some information from organizations such as American Cancer Society or similar organizations is ok but they should not be the main source of your information.

What is not appropriate?
  - Blogs
  - Wikipedia!
  - Videos or news pieces. Some professors may allow documentaries but you should always check first.
  - News articles. A single news article can be used as a starting point for a research paper but should not be a main source of information.

*** Be wary of web sites and organizations that claim there is a conspiracy or scientists are bought by companies to keep information hidden. Most of your information for a research paper should be coming from scientific articles and books. Do not rely only on web-based information from sources that are not familiar. If you are getting information from an organization that is not recognizable make sure to check the validity of the information presented! 

4. Write the paper in your own words! A research paper is not a collection of quotes connected together by a few words or sentences of your own. Once you've started gathering your sources, you should first read the source without taking notes. This will give you a good idea of what information is there and what is likely to be relevant to your paper. Then you can take your notes. Note at the top of your paper, the source, include all the information that you will need for your bibliography/end notes/work cited. Do not write in complete sentences and write the notes in your own words. You will find that there are some things that can't be rewritten in your own words. This does not mean you should quote the material. For example, many papers on AIDS and the virus that causes it has this sentence: Acquired immunodeficiency syndrome is caused by human immunodeficiency virus. There really isn't a way to write this any differently so you don't need to quote it. If you take notes in your own words then you will have to worry less about plagiarism.

When using information from a research paper, you do not need to write many details about how the experiment was done. What you should include is the relevant results and conclusions. Do not fill up your paper with extraneous words and information.

5. Organizing your notes will result in an organized paper. After writing notes of all the information from different sources, you should organize them so that the various pieces of information fit together. Often your professor will suggest that you make an outline. Here is a good explanation of an outline and how to put it together: What is an Outline? When writing your own outline you don't have to be so formal with Roman numerals, etc. but you should organize your thoughts before attempting to do any writing. Make sure you include your sources in your outline. You don't need the full reference but enough so you know where the information came from. This will help you to properly cite the sources when writing your paper (see #7).

6. Use transitions. When you are writing your paper, remember that the various sections should be linked together so that the paper flows. The last sentence of a paragraph should lead from that paragraph and into the topic of the next paragraph.

7. Properly cite your sources. Only listing your sources at the end of the paper is insufficient for a science research paper. You need to use in text citations. Make sure you use the proper format for your citations. Your professor will let you know what is required. For a science paper this will often be APA or AMA format. Here's a good resource of How and When to cite in a paper. And make sure to include your list of references at the end of your paper and in the proper format! Make sure you have the correct information. LOOK for the list of authors. If the source is a research paper in a journal you should have authors, title of the paper, year published (the month and day should not be included), journal name, volume, and page numbers.

8. Use correct spelling and proper grammar. This is a critical skill to learn. When you are out in the workforce, you want to be able to demonstrate that you do know what you are talking about! A poorly written letter/email/report will suggest that you do not. If you struggle with this, you should consult the tutors in the writing center. Also, read the paper out loud. You will often find your own mistakes when you actually hear them yourself!
      a. Avoid use of vernacular language. This is every day type of language. Words such as lots, a lot, got, gotten, etc. should be avoided. And it goes without saying that using texting type shorthand should NEVER be used!
      b. Make sure your tenses match. If you use the past tense make sure to use it throughout the paper. Generally when talking about research that was done in the past, the past tense should be used.
      c. Your subject and verb should match. This means that if you have more than one subject, the verb should be also for multiple subjects. For example: Chimpanzees have opposable thumbs. But also remember that inanimate subjects can't do anything. For example, when referencing a source, authors can state or conclude. The institutions in which the research was performed or the journal in which the paper was published cannot state or conclude.
       d. 15 words you should refrain from using!

9. Proofread your paper! Once you've written your paper you should set it aside for a few days. Then go back and reread the paper. You may even want to read the paper out loud. If it sounds weird or not right, correct it!

Sunday, November 17, 2013

Get your flu vaccine!

It's been way too long since I posted here (2 years??!??). This fall I'm teaching 4 classes for 3 community colleges on 4 different campuses! So life has been pretty crazy and there's not a lot of time to do much else, especially since 3 of the classes are new preps!

So while I think about what my next topic will be, and do the research, I encourage everyone to get their influenza vaccine! And if you can get your titers checked for pertussis (whooping cough), I recommend that as well. You may need a booster. Remember that the main goal of vaccines is protection of the population. There are many people who cannot be vaccinated because of underlying medical issues. As more people are vaccinated, there will be fewer susceptible people and the spread of the virus will be limited. The bonus is that you will be protected as well. The flu vaccine is not 100% effective; and many vaccines aren't. But if you do contract the virus, your symptoms will be less severe and the course of the disease will be shortened.

Friday, October 28, 2011

My 8th Marathon!

This past Sunday I ran the Delaware-Lehigh Heritage Marathon. It was my 8th marathon but the first in 8 years. Four of us, me, Jessi, Dave, and Ron, drove up the afternoon before to pick up our race packets. Had some ok beer at a brewery in Allentown and good Japanese food at another restaurant the night before. And of course - Jessi's cookies! The weather was perfect for a marathon - sunny, about 45-50 F at the start and warming up to about 60+ F by the time I finished.

The race course is very scenic. It is mostly on rail-trails along the Lehigh River. It is a relatively flat course with two noticeable hills - one short one to cross a bridge sometime after mile 10 and a steep one (~30% grade!!!) at mile 17.5. Though that statement needs a qualification as the course is actually a gradual uphill until mile 17.5 (thanks to Jessi's and Dave's Garmin data), then the race flattens out and becomes a downhill course.  After the big hill we ran along a ridge offering scenic views of the area and the Lehigh River. Good thing it wasn't raining or very windy because you are really exposed on that ridge.The one part of the course that I really didn't like (except for that steep hill! They really need to have some beer to reward us when we get to the top) was the multiple out and back at around mile 21. After running down from the ridge there is an aid station. You then run out about 1/2 - 3/4 of a mile then BACK to the aid station while passing the turn-off to the trail then back a bit where you are then running on the trail again.

This was the first time the marathon was run so there were bound to be some issues. The 30 min delayed start pissed off a lot of people. Especially those fast runners who had already done a warm-up and were now cooling down. But it gave me more time to hit the port-a-johns! And after drinking a whole 16 oz bottle of water I needed to pee again! The volunteers along the course did a great job and were enthusiastic. Along the ridge I had two girls shout out "Go NG!". Now this is a nick name that few people knew about so I knew that one of my friends who was running the race and wearing the same shirt as I asked the girls to do this. Thanks Ron! It is also a small race. There was a limit of 500 runners for both the full and the half-marathon and 125 people ran the marathon. Luckily, I have no problems running alone.

I had hoped that my 28 mile run in August with several 2-3 hr hilly runs (avg of 9 - 10.5 miles) in September and October would have been sufficient training but it definitely wasn't! I planned on running 10 min and walking 1 min; and I held to that for at least most of the first 10 miles. But I probably went out too fast - a 9:30 first mile! Early on my knees started aching and the muscle pains began. Why didn't I bring some Aleve with me??!? Occasionally I would walk 3-7 min in the hopes that it would help. But I think it just delayed finishing the race! I never felt that fatigued due to lack of energy. I was eating parts of a Power Bar, fruit chews, and drinking G2 Gatorade along the way. I was able to maintain good form - never did the marathon shuffle. When I walked I did so quickly. But people were passing me and I wasn't passing anyone else. As I approached the downhill to run the last 5-6 miles, one of the volunteers let me know that I was in last place. Oh well - not the first time that has happened. I made attempts to catch the runner in front of me and I was closing the gap! But I didn't have enough race left nor did I have any legs left to catch up. I definitely was running more than walking in the last miles of the race and actually ran to the finish line.

I finished in 5:24:35 (a personal worst) and last. Since its a small race, one of the volunteers quickly found my bag and brought it to me shortly after I finished. Jessi (placed first of the women - and had 2 hrs to rest before I finished) brought me a chair to sit down and some food - a turkey wrap, chili, and water. There was plenty of food at the end for the last runner and the volunteers to eat!

As expected, I hurt! The worst was the sharp pains in the front of the left ankle/lower shin. I was able to run without the ankle hurting but had sharp pains while walking during the race. I had a similar issue with the 50k in the Maylon Mayhem in August (except it was the right ankle then). Not sure what is causing this but I need to get it solved! Recovery has been pretty good. Did 25 min of yoga on Monday night - still able to touch the ground during a forward bend! Sore legs for about 2 days. And by Friday I think I'm ready for a run!

I'll run this race again. It's only about a 1.5 hr drive away (that is when Ron isn't driving) and hopefully I'll be able to do packet pick-up the morning of the race. But before I attempt another long road/non-technical trail race again there's a couple things that I need to do. The first is MORE MILES during training. I know that ultra runners think that time on the feet is sufficient but I know I need to do at least a couple of runs of distances of 15 miles or greater if I want to run most of a marathon and definitely if I want to finish it faster. The second is I need to lose some weight.

Dave, Jessi, me, and Ron. The shirts were quite popular!

Wednesday, September 21, 2011

Racing the trails in Morris County NJ

My friends have a race company that puts on trail races in various counties in New Jersey - check them out at NJ Trail Series. They are the only company that offers these types of races in NJ and races can cover distances from 5k to 100 miles and even up to 72 hrs! As race directors there are many issues they have to deal with. Permits to use various parks or facilities are, of course, one of them. The Morris County Parks Commission recently decided to not give NJ Trail Series permits to run three of their races due to the mistaken assumption that races of distances greater than 25 km (15.5 miles) is too risky. Many people who have participated in these and other NJ Trail Series races are writing letters to protest this decision. Here is the letter that I am going to send:

Dear Ms. Biase and members of the Morris County Parks Commission,

I am writing to you in response to your recent decisions to not allow NJ Trail Series to host three of their races in Morris County Parks (NJ Ultrafest, Mahlon Mayhem, and the Muddy Marathon) and to significantly increase the registration and permit fees for their other races, especially the 5k cross country series held at Central Ave Park.

NJ Trail Series has been the only company in New Jersey that is making trail races open to everyone. Their offerings of distances from 5K up to 100 miles increases participation to a wider range of people. Their attention to course markings, the safety of participants, and their focus on the fun of running in the woods has attracted people from many counties in NJ, many states in the USA (22 at the 2010 NJ Ultrafest!), and countries around the world! The race directors, Jennifer and Rick McNulty, care about every runner on the course and will wait for every participant to finish, no matter how long it may take them. This is not true of many road races. Marathons close their course after a certain time period. If you are still on the course of these other races, you are left to your own devices to get to the finish and without aid. NJ Trail Series supplies aid the entire time runners are on the course and does not leave anyone or anything on the course. Volunteers for the NJ Trail Series races run the course at the end of the race to pick up every flag and ribbon used on the course.

Many people have the mistaken assumption that running longer distances (ie. the arbitrary 25 km limit set by Morris County Parks Commission) are detrimental to health and is considered risky behavior. This is far from true.  Yes there are instances of someone dying while running marathons or participating in triathalons. This can occur whether on the race course, while training, on the road or in the woods. All of us who are running the longer distances of some of the NJ Trail Series races, including the three races that were denied permits by the Morris County Parks Commission, have trained for these distances. We have undertaken months of running longer distances on the roads and on the trails, many on the trails in Morris County, to prepare for these races. As adults, we understand the risks of running long distances and running on trails.

The 5k cross country race at Central Ave Park exposes runners of all ages to the race environment. Runners as young as 7 yrs and as old as 74 yrs participate. This is a low key (and low entry fee) race that anyone can run. To charge a small, family-owned, company $150/race to utilize the course is outrageous. The park is rarely used on a Wednesday evening by Morris County residents who aren’t racing; the dodgeball participants have use of the upper parking lot since most runners park on the street; and those who are there aren’t restricted from using the site or the facilities. The county provides very little ammenities to justify this fee. There are portable toilets provided, along with the permanent bathroom facilities; however, the toilets were removed and not replaced for 3 weeks this year, and these are open for anyone that frequents the park Monday-Sunday, not just race participants.

What has running NJ Trail Series done for me? It has gotten me back into running more often and longer distances, encouraged me to see what my limits might be and allowed me to run my first ultramarathon (two 50 km races this year!). I have observed the strength and vitality of other runners who are running very long distances and setting records (US records have been set at NJ Trail Series races!), assisted other runners in achieving their goals through volunteer work and support and assistance of other runners on the course, and have met people and made new friends

“I run mostly to see things, to explore places I don't know. And the places I do know, like around here, then I get a sense of the weather, the shifting light, the seasonal changes; it can be pleasurable even when you hurl yourself into the teeth of nature. “
- Edward Koren, Artist/New Yorker cartoonist.
Everyone I know that runs trail races embrace this sentiment.
Please reinstate the permits for the NJ Trail Series races that were to be held in Morris County Parks in 2012 – NJ Ultrafest, Mahlon Mayhem, and the Muddy Marathon!
I’d be happy to answer any questions you have about my views on NJ Trail Series races – or trail running in general. I am very familiar with the races as I have run or volunteered at nearly every NJ Trail Series race and have participated in numerous other races.
Anne Pumfery

Thursday, June 30, 2011

Why was Avastin pulled by the FDA for treatment of breast cancer?

I was reading a piece in The Star-Ledger this morning and came across a news piece written by a Washington Post reporter ( about the FDA ending the use of Avastin to treat metastatic breast cancer. The reason that the FDA is pulling the drug (according to the above news piece) is “…that the drug was harming women more than it was helping them.” The remainder of the article discussed the price of the drug ($88,000/year/patient) and the outcry from patients and advocates for access to new treatments. It was stated that clinical trials failed to support the drug’s promise to treat breast cancer but at no point does the reporter tell readers the harmful side-effects that prompted the FDA to remove approval of the drug for breast cancer treatment. I think these two pieces of information are quite important to understand the FDA’s decision. However, the use of Avastin to treat colon, lung, kidney, and brain cancers is not in jeopardy.

So let’s start with how Avastin is supposed to work to treat cancers (I’ll post at the bottom of this page the links to where I obtained my information for anyone who wants to learn more). Avastin is also known as bevacizumab. It is an injectable cancer medication that works by blocking a protein that is important for the formation of blood vessels. This is a method for targeting solid tumors since the cells that are in the interior of the tumor need a supply of nutrients, which are brought in via new blood vessels. As tumors get larger, the cancer cells start expressing proteins that will induce cells of the body to generate new blood vessels. In 1971, Dr. Judah Folkman of Harvard Medical School first proposed that large tumors need these blood vessels to grow and metastasize, which he called angiogenesis. He also proposed that inhibiting angiogenesis may be one way to treat cancer – besides inhibiting cellular replication. His research and the work of others over the years led to the discovery of several proteins that cause angiogenesis. One of these proteins is VEGF (vascular endothelial growth factor) which is the target for the drug Avastin. Patients whose breast tumors express VEGF in high quantities have a poor prognosis, so VEGF should be a very good drug target. Avastin binds to all forms of VEGF in the blood which prevents VEGF from binding to its receptors and functioning to induce blood vessel formation. However, this drug has little effect on its own in treating breast cancer but does help to increase the efficacy of other drugs that inhibit cell growth such as paclitaxel. But more importantly, the combination only extended overall survival by less than one year! An increase of survival of less than one year does not seem like much of an improvement; and this would be especially true if there are any serious side effects associated with use of the drug.

So what are the side effects, how often are they observed in patients, and how significant are these side effects? Side effects observed included kidney damage, development of holes in parts of the body (for example, nose, stomach, intestines), massive bleeding requiring blood transfusions, and various cardiovascular problems (for example, heart attack, stroke, clotting in arteries, chest pain, and reduced blood flow to the brain). These are pretty serious side-effects that can cause death or brain damage. The rate of severe or life-threatening side effects was 14-20% higher in patients who were on Avastin plus chemotherapy as compared to patients on chemotherapy alone. Additionally, there was an increase risk of treatment related deaths in patients receiving Avastin with chemotherapy as compared to chemotherapy alone.

So because there was very little benefit and significant risk to patients taking Avastin, the FDA rightly pulled the approval of using this drug to treat metastatic breast cancer. These results are also a good example of why accelerated approval of drugs is not necessarily a good thing. Accelerated approval allows earlier approval of drugs to treat serious diseases, and that fill an unmet medical need. Generally clinical trials results are based on clinical outcomes (ie. prolonged survival or years disease-free) and obtaining these types of results can take a very long time. Accelerated approval of drugs started when AIDS activists pushed to have anti-retroviral drugs approved at a faster rate for treating AIDS. At the time, there were no treatment options for HIV infected patients except to treat the opportunistic infections that these individuals would get due to their suppressed immune system. So we have the balance the good (getting new and better drugs to patients at a faster rate) and the bad (may not observe some of the severe side-effects or treatment-associated deaths during shortened clinical trials) when deciding whether accelerated approval of a drug should occur.

Additional information:

Encyclopedia Britannica article on angiogenesis:
Paper by L.S. Rosen, H.L. Ashurst, and L. Chap discussing treatments for metastatic breast cancer:

Genentech’s (manufacturer of Avastin) website for Avastin:

Thursday, March 24, 2011

Thoughts from my first 50 km race

Last Saturday I ran my first 50 km race at the NJ Ultra Festival that was put on by NJ Trail Series ( Though this wasn’t actually my first ultra distance, having completed 27 miles at the 2010 12 hr fat-ass at the Parsippany Hills track, it was my first 50 km race. I made it to the Long Valley Presbyterian Church early Friday evening and saw lots of friends who were going to be running a variety of distances from 50 km to 100 miles! Jessi Kennedy and Dave Lettieri were running the 100 mile race – as was Johnny Rodriguez who I first met in August at the Mahlon-Mayhem; Jonathon Wilson, Dave Kravitz, Dave Monzella, and Ron Redfield were going to be running the 50 km “with” me. With is in quotes as I knew all of them were going to finish way ahead of me. It was interesting to hear the nervousness from some of the runners and I kept thinking to myself “Why am I not feeling the same concern”. It was my first 50 km race and the last time I ran a marathon was seven years ago! Plus my longest training run was 16.5 miles – 13.1 miles at Lewis Morris Park which isn’t a place that is easy for straight running and then 3.4 miles in Kearny – not exactly the best training for a 50 km race. But I also knew I had all day to complete the distance (goal #1) and that I’ve ran my last marathon with probably less training. Surprisingly, I also thought I should be able to do this in about 7 hrs (but secretly hoping for 6 hrs).

Race morning started with me not wanting to get out of bed at 5:45 AM so I slept in for another 15 minutes. Probably a mistake since I still had to find breakfast – which I was able to do at a bagel shop about ½ mile from the hotel. I ate the bagel and drank coffee on the drive back to the church, neither of which I finished before the start. I dropped my stuff off at the start with a few minutes to spare. It was quite chilly so I donned a double layered fleece that I picked up recently. I figured if I got too warm I can always tie it around my waist.  We all received directions from the race director, Jennifer McNulty, and we were off. I started running with Dave K. at a comfortable pace of about 11 min/mile, according to his Garmin, till we hit the turn-around 3 miles later. Both of us needed to make a pit stop and at this point it was time for me to walk a bit. My strategy was to do timed run-walks. I kept debating how long I was going to run before walking – 15 minutes won out. I was running well, though my shoes kept bothering me – my toes were getting numb. This is a common occurrence for me with new shoes until they are broken in or I’ve figured the correct tightness of the laces. Luckily the course had the 50 km runners going back to the start-finish two times before we finished so I was able to change out to another pair of shoes that I brought. Of course this was a huge leap of faith on my part since I had run all of 6 miles on these shoes. I also switched out the fleece and put on the windbreaker. I was debating whether or not to wear the windbreaker but I’m glad I did – every so often clouds would obscure the sun and the wind would pick up and I would get cold.

So 6 miles done, 25 more to go! Of course the new shoes were giving me issues but not as much as the first pair. During my walk breaks I would untie my shoes to loosen up the laces. A couple times of doing that did the trick and I was able to run without any shoe issues for the rest of the race – though it wasn’t the end of my foot issues. After a while (not sure at what mileage – was I still on the western loop? Or back on the eastern loop?), my feet really started hurting. This was likely due to the lack of training and the fact that I am carrying an extra 20 pounds or so for these distances!  So I continued my run-walk, eating cut-up bits of Cliff bars and drinking water and feeling pretty good for the 15 miles or so until I ran into John Coffey who was walking as well. So I chatted with John for about 5 minutes and then I was back to running.  At this point I thought I was doing pretty well since John usually finishes races before me (and he did again, passing me for the last time towards the end of the western loop). At some point I started struggling, so I switched to 10 min run – 1 min walk, then to 5-1, and then to running when I felt good enough. I figured I was struggling because of the lack of training, but based on how I felt after getting some food at the start-finish, it was likely due to lack of food. Earlier at one of the aid stations, I ate two raspberries and all of a sudden my stomach tightened up. Not good since I still had a lot of race left! I was also getting really tired of my Cliff bar bits (I had cut a Cliff bar into 6-8 bite-size pieces and put them in a ziplock bag). So at the aid stations I would grab a strawberry or two, pick out several jelly bellies that I knew I would like (some of their flavors are just nasty!) and continue on the run. Not the best nutrition but I always felt I had energy to continue running – got to love those simple sugars that get into your blood stream quickly!

So I finished the western loop and had 9 more miles to run. Ugh! I was seriously hurting at this time – feet, legs, hips, back – you name the body part it hurt! So I just finished running much more than my training and I knew the last 9 miles were going to be a struggle. But I knew I would finish even if I had to walk the entire distance! Which of course I would never let myself do. I was hoping to keep at least a few 50 km racers behind me. I’ve been ok with finishing DFL in several races this past year but that day was not going to be one of those days! So as I continued running for a bit and walking even more, I spied a woman about a quarter mile ahead of me and I could see she was struggling. So my goal was to catch up and pass her! And I did! But at some point she ended up catching up to me again. Darn! I talked with her for a while to find out she was also running her first 50 km race. And she never ran a marathon before this, which I find totally amazing since I know how difficult a marathon could be! So while we were chatting I saw Jonathon running towards me. He had already finished his 50 km race and he decided he would run the last couple miles with me. Thanks Jon! And then Dave, who was running his first 100 mile race, joined us as well. It was nice to be running with friends again since I ran alone most of the race. Though never truly alone as I kept seeing people running in the opposite direction – we would give each other a thumbs up or a “nice job” – or someone would pass me.  So after chatting with my “competition” for a while I was back to running – and walking – with Jon. After turning the corner to the straightaway to the end, I found myself picking up the pace and “sprinting” to the finish. I finished in 7hr 11 min! Pretty much hit my target! I figured I would have been emotional about finishing my first 50 km race but I wasn’t. But I was definitely proud of what I had accomplished – and had a post-race celebration beer with friends at the race. Not everyone can run that far!

Of course, I was exhausted and quite sore but that evening I was already thinking about next year! I know that I can run faster and my training wasn’t optimal. I also need to think more about nutrition and plan better. Grabbing a bagel and coffee 45 minutes before the start of the race is not ideal. But I also have to think about nutrition during the course. The Cliff bars were pretty good but I probably need to carry something that is more readily digestible and probably should eat more often. I know a lot of people eat gels, but the thought of "eating" a think gel does not sound appealing. Though the thought of eating Powerbars used to not appeal to me, until I started long distance training and races and needed to carry food with me. So maybe I should give gels a try. I just have to find ones that I like.

I’ve already registered for my next looong distance race. I’ll be running for 12 hrs at 3 Days at the Fair in May – another race put on by NJ Trail Series. I wonder how far I'll run - 50 miles perhaps?