Friday, August 20, 2010
A visit to Robo Lab was a great way to start the week. As someone who is interested in high-throughput operations, this lab offered a glimpse into the way hundreds of thousands of samples can be tracked and processed every day. Although the system works fairly well, there are still major issues that need to be addressed, and the efficiency should go up significantly with renovations and upgrades scheduled for next year. Some of the problems with the current system were obvious (e.g. physically moving samples across long distances rather than drawing multiple samples from tubes in a single location), while other problems were more difficult to spot (e.g. using mechanical tracks that are prone to malfunctioning or contain parts that readily wear out, and using systems from multiple suppliers/manufacturers so cohesiveness becomes an issue and technical support can be difficult to receive). It was also interesting to see the way the samples are transported through the hospital via a vacuum tube system. It would be nice to see the updated and condensed Robo Lab a few years from now.
Before selecting the genes of interest for my qPCR, I spoke with a researcher in the lab who has done studies on wound healing in mouse lung and liver samples. Based on our conversation, nearly a dozen genes were identified for analysis. The first step in ordering primers is to consult the National Center for Biotechnology Information (NCBI) database in order to identify the loci of genes as well as to find the sequence. The Harvard Primer Bank is then used to identify primers that others have reported as being useful when amplifying the gene of interest. Since others in the lab will likely use these stocks of primers for cell cultures containing both human and mouse cells, it is important to use the Basic Local Alignment Search Tool (BLAST) to verify that both the forward and reverse primer for each gene is a 100% match for the mouse gene and at least one of the two primers is not a match for the human gene. Once this is done, the primer can be ordered. Once the primers arrived, the stocks were diluted to a standard concentration, the concentration of the RNA was analyzed, cDNA was made from the RNA, and the qPCR was run. Eleven genes were analyzed along with one house-keeping gene for normalization of the results.
A preliminary review of the data has revealed which genes were up regulated and which were down regulated as a result of 45 hours in the bioreactor, and a third tissue set, involving a different media, has provided even more interesting results. Unfortunately, the company hold the components of the media as a trade secret, so it will be difficult to form a strong hypotheses as to why the change in media resulted in such a dramatic change in genetic regulation.
Summer Immersion has been a wonderful experience that has helped shape my outlook on biomedical engineering. Thank you to everyone who has helped make this possible. I look forward to hearing about the experiences next year's class will have during immersion.
In addition to lab work Tuesday I was able to attend medicine grand rounds in which Dr. Muthukumar presented a lecture on "Why Organs Fail? Molecular mechanisms of Fibrosis". His discussion of cellular differentiation complemented what I had been learning in the lab, so it was well worth skipping lunch in order to attend the lecture. Much of the rest of the day was spent reading papers.
On Wednesday I was able to make histology slides from the frozen lung tissue, and I learned that it is best to inject the lungs prior to freezing to ensure they do not fall apart or shred during slicing. Unfortunately, everyone I had spoken to had omitted this step when describing the protocol, so I was left with samples that provided a bit of a challenge. Thankfully, although the process became more time consuming, good sections appear to have been produced, and any slides I make in the future will likely seem easy by comparison. This is probably the best way to learn.
Wednesday evening I was able to attend a second MRI class in which we learned how to scan the head and abdomen. It was very interesting to see the limits of the "breath hold" technique, and I now have a greater appreciation for the work done by programmers in order to reduce motion artifacts. It was nice to learn more about the fundamentals of MRI (T1 vs T2, how to get Susceptibility SPGR images and Axial FLAIR scans, in-phase vs. out-of-phase, etc.). Again, the manual for the course was very easy to follow and made the laboratory portion of the course quite enjoyable.
Thursday I was able to treat the slides with hematoxylin and eosin (H&E) stain then leave them overnight to dry, and Friday I was able to look at the slides and plan out the next stages of the project with my research mentor in better detail.
Note: The above image is from http://drsvenkatesan.files.wordpress.com/2009/04/gunther-tulip-ivc-filter.jpg
Saturday, August 14, 2010
Tuesday, August 10, 2010
The experience was not as fun as the rest of summer immersion; apparently watching surgery, imaging, and lab tests are more fun than having them performed on you. Over the course of my treatment I ended up receiving a CT Scan, an MRI, and several x-rays. While all of these imaging procedures were painless and easy the entire process of getting all the appointments did take weeks to complete. I’m not sure where the engineering solution lies, but it seems like this whole process could be streamlined and made more efficient by somehow providing patients quicker access to these tools.
After eventually obtaining all of the imaging needed to decide on a proper course of action two surgeons both suggested the same procedure. They told me my wrist was most likely to heal quickly and correctly if an autograft from my hip was taken and inserted into the space between the fractured bones. This whole mess would then be screwed closed and I’d be left with some cool new hardware and a sweet scar. After going through the information I consented to the procedure and scheduled to have it done.
The process of actually going for the surgery wasn’t too bad. The only difficult part was actually walking into the OR and seeing everybody surrounding me. Having been on the opposite side I never realized how overwhelming the number of people present for a surgery could be. With everyone busy around me doing all sorts of different things; including sticking me with needles and getting scalpels ready it was difficult to remain calm. Eventually they put me under anesthesia though and I’m a little fuzzy on the details from there on.
Recovery has progressed quickly considering all that was done. My wrist is already painless, though the bone will take months in a cast to heal fully. My hip hurt a lot at first, but is also rapidly returning to normal. After surgery I was able to return to work the next day; albeit in a little more pain; and accomplish some paperwork on my research project. While the project is not completely finished I’ve made some considerable progress towards completing it and both advisors in New York and Ithaca seem happy with my progress.
Finally receiving the surgery I needed made an excellent end to summer immersion showing me medicine from the other side. As a patient myself it was immediately much easier to relate. My research project with Dr. Cesarman provided me access to a more clinical side of research then I’ve ever seen and taught me a toolbox of new techniques. Overall my progress has been successful and hopefully with a little more work will lead to publication. Further, we’ve received a small pilot grant through the Weill Cornell Clinical and Translational Pilot center to continue the project.
This program has provided an excellent opportunity and served as a great crash course in medicine. During these seven weeks I was able to learn much more than if I had remained in Ithaca and the experience has helped me develop as a researcher. Thanks to Dr. Wang, Dr. Frayer, Belinda Floyd, and Mitch Cooper for all their time setting this program up; it ran great!
The first task didn’t appear too difficult, but as I began I realized it was going to be hard to detect whether or not my oligonucleotides attached to the gold nanoparticles. I had thought the added mass of the oligonucleotides would cause a shift in the SPR of the particles, but realized because my oligonucleotides were short this wasn’t going to be the case. The aggregation of gold particles would still work; I just needed another method of determining whether the first step of my preparation had completed.
Ultimately I came up with another test to determine whether the oligonucleotides attached to the gold nanoparticles. Specifically, gold nanoparticles react with salt and precipitate out of solution. However, if the surface of the particles is protected by oligonucleotides the particles remain stable in suspension. This stability is also particularly important because DNA hybridization is normally performed in the presence of salt, and will be required for the next step. By running an array of samples changing the concentration of salt and whether or not oligonucleotides had been bound to the gold nanoparticles I was able to confirm their presence. Looking at the figure the gold nanoparticles with no nucleotides rapidly precipitate out of suspension and the solution loses its color. However, once a monolayer of oligonucleotides is attached to the particles they remain in suspension for days.
The next step is to actually test these nanoparticles with DNA from cell lines infected with the virus and see if I can get a color change reaction. So far I’ve been unsuccessful, but I have another week to try. I think the problem might be the proximity of the gold nanoparticles; even though the lengths of DNA I chose closely match the literature I’m worried the particles are still too far. I have some particles with larger radii which I plan on trying which might help alleviate this problem.
This week I also visited the Emergency Room which so far has been one of my favorite places in the hospital. I really enjoyed the fast pace of and was able to see how quick, easy to use technology would really benefit the patients here. I continued in pathology too and observed more patients and cases. I also saw a mortality conference on one case I had followed and was really interested to see all of the information presented together. Another great week in New York!
By week five enough of my materials had arrived to start experiments. I had obtained my gold nanoparticles and my PCR Primers, though not some specific thiol modified oligonucleotides. Just a recap, I’m working on a detection mechanism for Kaposi’s Sarcoma causing herpes virus based on changes in the optical properties of gold nano particles when they aggregate and are packed tightly together. By functionalizing the gold nanoparticles with two different oligonucleotides which are non complimentary and then introducing a third oligonucleotide which is complimentary to both the particles can be caused to aggregate. If this third oligonucleotide is from a virus such a scheme could be used to determine whether or not the virus is present.
Because the thiol modified oligonucleotides hadn’t arrived yet I started with regular oligonucleotides I had ordered with the same sequences which could be used for PCR. Using these PCR Primers I should be able to detect viral DNA using more conventional means and test whether or not my DNA sequences will actually detect KSHV and nothing else. DNA was extracted from two cell lines, one positive for KSHV and one not, and also from a mouse tail clipping. The DNA was prepared for PCR with my primers and the results were run through a gel.
The results came out positive; only the cell line positive for KSHV showed the PCR product while all other cell lines and a water control were negative. The product was the right size given the primers and was seen in both KSHV positive samples.
My clinical experiences continued on as normal this week and I observed more brain dissections and histology. Overall this was another successful week and I was happy to begin making real progress in my research.
Monday, August 9, 2010
I wrapped up my time with Dr. Doty by cataloguing some histology by cut, stain, and spinal structure. I became very familiar with how a vertebrae looks under various types of staining as opposed to how a soft tissue, such as the intervertebral disc would look. It was interesting to learn what types of you staining you might want to use when evaluating different tissues in the body. We were unable to schedule another MRI class, but the workbooks we recieved in addition to the previous training more than made up for it.
I ended the week much the same way as I started the Immersion term: watching surgery and seeing patients. I observed a L5-S1 spinal fusion with the use of a special technology developed by SpineWave. Dr. Hartl used the StaXX XD expandable device to aid in restoring disc space height after the discectomy. This system allows for controlled distraction of the disc space in 1 mm increments via a simple ratcheting device. Additionally, this system is minimally invasive. After the device was implanted, rods and screws were then used to correct scoliosis in the spine.
In just this short immersion term, I have learn much about the in-depth anatomy of the spine, breadth of spinal traumas that extend past the scope of my research project, and have truly gained insight into how my research at Cornell can translate to a beneficial clinical result. I can honestly say that this experience has helped to reshape my thinking about my Ph.D thesis, and I hope for continued collaboration with Dr. Hartl throughout my tenure at Cornell.
The "hook-up" was only mildly uncomfortable: the scalp has to be scoured with alcohol to ensure firm electrode connection. Despite the multitude of connections and wires, it wasn't too cumbersome. However, I experienced a good deal of difficulty falling asleep. This phenomenon is so frequently encountered that it has its own name: the "first night effect." Participants in sleep studies often experience difficulty falling asleep. If the study is conducted for more than a single night, the subjects often acclimate to their new surroundings and sleep soundly. I recall repeatedly being on the verge of sleep only to awaken abruptly with a spastic twitch, much like when trying to stay awake when tired in a lecture. It was as a result of one of these spastic, involuntary twitches that I jerked the finger pulse oximeter loose, prompting one of the technicians to enter to reconnect it. After a fitful night's sleep, I was awakened by one of the technicians. Feeling not at all refreshed, I dressed, walked back to my dormitory, and sunk into a deep sleep.
Later in the day, I was able to sit through the scoring of my sleep quality with one of the technicians. It was definitely a unique ̶ and somewhat unnerving ̶ experience viewing myself on the video. Initially, I had been concerned that I had "failed" the sleep test. Upon waking in the morning, I was firmly convinced that I hadn't slept at all, or at most, only dozed off. I had, in fact, slept for 3 hours and 45 minutes, enough for an assessment to be made.
Much to my surprise and relief, it turns out that I don't have sleep apnea. The index for number of breathing events was well within the normal range. Specifically, my Apnea/Hypopnea (A/H) index was 1.1. Sleep apnea is considered mild if 5-15 such events occur per hour. Moderate in the range of 15-30 events per hour. Severe is above 30 events per hour. While it seems that I am clear of sleep apnea, I was cautioned that sleep apnea tends to be more severe during REM sleep and due to the disturbed nature of my sleep, I experienced only a modest about of REM sleep (about 15 min). However, during this period of REM sleep, no episodes manifested. Also, I stayed on my back (the supine position) for most of the night. As sleep apnea is most severe in the supine position, I don't have to fear the assessment was skewed by my body position.
There was one unnerving breathing episode in which I appeared to stop breathing for an entire minute. The distinction between obstructive and central sleep apnea is an easy one to make. In central apnea, the chest fails to expand (a nervous system condition). In obstructive apnea, the chest continues to rise and fall, but air is unable to be drawn into the lungs. In this one minute cessation of breathing, my chest was seen to rise and fall, so this was an example ̶ and a disconcertingly long one at that ̶ of obstructive sleep apnea. When breathing resumed, I was seen to stir, being momentarily awakened. While it may sound alarming, my saturated blood oxygen level (SaO2) barely dipped in the aftermath of this breathing cessation. The technician explained that in some people, such as those with chronic obstructive pulmonary disease (COPD), such a breathing episode would be followed by a precipitous drop in SaO2. Throughout the course of the night, my SaO2 levels remained in the high 90s. Also, much to my surprise, it turns out that I do not snore.
While sleep apnea was ruled out, I was still left wondering what may account for my daytime drowsiness. Another technician looked at my sleep study and identified it as a textbook case of "delayed sleep phase syndrome." DSPS is a "circadian rhythm sleep disorder, a chronic disorder of the timing of sleep, peak period of alertness, the core body temperature rhythm, hormonal and other daily rhythms relative to societal requirements." People with this condition report being unable to fall asleep until early morning and find it difficult to wake early for their obligations and commitments. There are a number of ways to remedy this condition, mostly through lifestyle modifications. These changes include abstaining from caffeine after noon, not engaging in strenuous physical exercise in the evening, and adherence to a strict sleep regimen. My lifestyle was definitely not following these simple rules as I would routinely consume caffeine throughout the day, lift weights late at night (thinking it might serve to tire me out), and had little regularity in my sleep cycle due to the changes in my workload.
I enjoyed my summer immersion experience at Weill Cornell and have a newfound respect for physicians and support staff who must interact with the sick on a routine basis. I now appreciate just how hectic their lives are and the pressing need that exists for engineers to provide superior devices to shorten wait times when every second matters and to lengthen patients' lives when every extra day is cherished.
Tuesday, August 3, 2010
For my final week here in NYP I worked mostly on my research project since the sodium oxalate I ordered finally came in. So I spent my time in lab testing out different responses to different concentrations of sodium oxalate and calcium chloride. In all my tests whether or not I submerged a stainless steel paperclip in the solution, there was precipitation at some point of calcium oxalate. For most of my tests involving lithogenesis with paper clips I tried to establish a concentrations of .5 mM of sodium oxalate and calcium chloride under constant stirring. My experiments ranged from 2 hours to 24 hours just to see the effects and I am happy to report that the paperclips have all calcified to the degree positively correlated to the experiment run time. Knowing that lithogenic metal undergoes lithogenesis in this experiment helps me establish a positive control for future experiments. I also hope to obtain a calcium ion-selective electrode in the future to help me quantify the calcium ion concentration in solution over time for a more quantitative result as well as take SEM pictures of the crystals formed on the clips. Once this has been established I will move on to testing lithogenesis on various elastomeric biomaterials for potential use in an artificial bladder.
I also saw the last part of a complex surgery this week on a male patient in his 60's who was suffering from renal cancer designated T3c. The tumor had spread all the way from his left kidney up into the inferior vena cava; this was a joint surgery between my mentor Dr. Scherr and Dr. Giradi who was a cardiac surgeon. Briefly, in order to fully remove the tumor they had to divert blood away from the heart using a machine in to stop the heart and allow the doctors to push the tumor out of heart so that they could remove the whole tumor at once. The head was iced and the blood was cooled by the machine to prevent neural damage during this part of the procedure. Once the tumor was removed the doctors worked to reperfuse the heart and warm up the body to allow the patient to natural circulate his blood. They inserted a temporary pacemaker into the patient to help coordinate his pace with his reperfusion.
I would like to sincerely thank my mentor Dr. Scherr and all of his residents for being patient with me and showing a great time in the OR and hospital. I have learned a lot here and of the importance of developing technologies to aid in medical care and treatment, I will carry this motivation forwards with me as I continue on my PhD research career. I would also like to thank Dr. Frayer and Dr. Wang for organizing this whole summer endeavor and treating the whole BME class to a delicious farewell dinner. May all the Cornell BME students prosper in the years to come!!!
Monday, August 2, 2010
In addition, I had a few conference calls with my Mentor and GE to discuss future collaboration this fall, and it looks like I will be getting a paper out of the work I did this summer, and future work I will do this fall.
All in all, this summer has been a great experience. I was able to see Cardiac MRI, Cardiac Electro-physiology, Cardiac Echo (and TEE), open-heart-surgery, rounds in the CCICU, rounds in Cardiac Telemetry, Nuclear Imaging and Nuclear stress tests, and finally a pacemaker implant. Being able to see all of these activities in Cardiology, has definitely helped me gain insight into both how the heart works when healthy and also how the heart works and is fixed in diseased states. I now am more aware of the clinical aspect of my PhD research in Cardiac MRI. Thanks again to Drs. Wang and Frayer for organizing immersion.
Sunday, August 1, 2010
Over the last few weeks I have been able to see how doctors use technology to improve healthcare for their patients. Biomedical engineers do research in technology that has direct applications in the medical field and this experience is not only important for gaining an appreciation and sense of where future developments will be needed, but it also helps to foster collaborations between physicians and students like me. My summer project for example was very applicable to what I will be continuing to study in future research; where I am facing many similar mathematical problems and using many of the same tools. I feel very fortunate that over the summer I was able to observe how technology works with medicine in modern healthcare. I was able to see many aspects of healthcare from seeing patients with Dr. Gauthier, reading neurological images with Dr. Comunale to observing how this kind of information was used in the OR with Dr. Greenfield and Dr. Kaplitt in neurosurgery. Beyond neurology I also saw the importance of imaging modalities in other departments of the hospital; primarily in pathology, urology, the intensive care unit and cardiothoracic surgery. These experiences helped me to understand how doctors in other departments use technology including imaging in their clinical cases. To observe these complicated procedures and clinical activities was no easy task; it required some study on the problems that these doctors face and the vocabulary that these doctors use to communicate their activities and situations. This was probably the most difficult task over the summer. It took some effort to study and ask enough questions about the situations in order to understand enough about the clinical situation to be able to understand the doctors’ point of view and the challenges that they face during their procedures. Once I could understand these challenges I could really see the synergy between the science of medicine and the aid that current technology provides.
My project in a way helps with this goal. My project will help Dr. Gauthier in the research that her group is doing to understand what happens in MS lesions during the progression of the disease; and I may be a contributing author on a paper the group is currently writing on T2 relaxometry. Earlier in the week I was able to present what I was able to accomplish over the summer in a meeting to all of the immersion students and advisors for the program. I was able to show how the fitting algorithms that I was working with work with some of the data that I have in both the mouse scans that were taken earlier in the summer and with some human data.
I am very grateful for the unique opportunity that I was able to have over the summer I have learned so much about a field I otherwise would never have been able to observe. This experience has taught me so much and I am grateful for the generosity and patience that the nurses, surgeons and doctors showed me, Thank you.
My research project from this summer will hopefully lead to a manuscript with both biomedical engineering and clinical aspects: prostate cancer cell line characterizations (MDA-PCa-2b) and circulating tumor cell capture and culture from patient samples with known stages of metastasis, respectively. Dr. Nanus’s lab and our lab have also established collaboration based on this project and I look forward to presenting our results at the upcoming PS-OC conferences.
Again, special thanks go to people who organized the summer immersion and made all these wonderful experience happen: Dr. Yi Wang, Dr. Frayer, Dr. Nanus, Mitch Cooper, and all the doctors and nurses who let me observe in their ORs/ER/NICU.
Although this is the final week of our Summer Immersion, I can confidently say that the insights, skills, and lessons learned from this experience will continue to enrich my career and perspective for many years to come. Not only was I able to observe a variety of surgeries in the OR across a range of departments (plastic, pediatric, cardiac, etc.), but I was also able to witness grand rounds debates, accompany the residents during patient rounds, attend general surgery lectures, visit the ER and NICU, learn to perform MRI scans and other diagnostic tests, and watch patients progress over the 7 week period from a highly invasive surgery to an almost completely healed state. My mentor, Dr. Grant, was an amazing teacher - I could not have asked for a more knowledgeable and enthusiastic guide to help me along my first steps into the clinical world and to help me understand the trials and tribulations of patient care. Moreover, my experience was slightly different than that of my peers because I had the opportunity to visit both Cornell and Columbia medical hospitals and interact with surgeons and residents in both locations. What few of us may realize is that different hospitals do things differently with regards to patient care. Yes, there are institutionalized rules and standards that must be followed…but if you pay attention, you will see that there are numerous subtle differences in the way hospitals design their residency program, the way ER nurses screen walk-in patients in the ER, and even in the way residents and surgeons go about performing surgeries in the OR (in terms of what instruments they prefer to use, how they position the patient, how they plan their incisions, etc.).
Lastly, I would like to thank everyone in the BME department, Cornell Medical Hospital, Columbia Medical Hospital, all my friends, and my clinician mentor Dr. Robert Grant, for supporting my adventure into the clinical and applied side of Biomedical Engineering. Overall, this Summer Immersion was a wonderful, eye-opening experience!
After the dehydration process was completed the each femurs was cut with IsoMet ® 1000 Precision Saw. Using the IsoMet®, each femur was cut at the three different positions: at the middle, at positions 7.0 mm, and 15 mm. Both hands were used for the first cut; later cuts were made by programing the machine. The metal implant was cut at position 7mm and 15mm. The optimal speed was 150 rpm.After cutting each individual femur, they were characterized by using the Scanning Electron Microscope (SEM), histology studies and mechanical testing.
In order to calculate the displacement of the vertebra, a human lumbar spine of a three years old male cadaver was used. Saline solution was used to keep it hydrated. Clay was placed at each end of the vertebra and a metal platform was screwed. A total of 10 rod pins with reflector tape at the end of each rod. The vertebra was placed in the Bionix ®EM Test System.
The clinical summer immersion program at Weill Medical College of Cornell University was a transforming experience. It was able to give me a clear understanding of how people’s lives are impacted through my PhD research. Each surgery and rounds that I attended made a change in my personal career. At the end of the seven weeks, I was able to understand the vocabulary that medical doctors used. Also, I was highly impressed with the advance technology that the HSS and Weill Cornell Medical College are using to improve people’s health.
Saturday, July 31, 2010
This week was my last visit to the Center for Skeletal Dysplasia with Dr. Raggio. There were fewer patients seen during the day than usual. One of the patients was a ~30-year-old woman who has been living with osteogenesis imperfecta (OI) Type I. Because she was a new patient, she did not feel comfortable with students coming into the room during the examination. However, I was able to see her for a few minutes and learned more about her during the patient conference afterwards. She actually leads a fairly normal life, and her stature at 4’ 10” is right around the level to not even be considered a little person. She is a great success story for OI. Her reason for contacting the center was just to make sure that she is doing everything she can to lead a healthy, normal life. Her fractures have been few and far in between, with the last occurring over a decade ago. Dr. Raggio wanted to have some x-rays and blood work done to take a look at her bones and to measure her calcium and vitamin D levels, just to keep her in check. Since I went to the center for three straight weeks, it was definitely one of my favorite experiences during summer immersion. I think the team involved really does care about the patients they treat, and it makes all the difference.
My project also took up a lot of time this week. I wanted to be sure that I had all the data and information necessary to move forward with the statistics. Earlier, I had begun to run some preliminary statistics on the scores for each region of the knee implants for both the med student’s and my grades. Also, I did a lot of background reading on the wear ratings for implants to get a good idea of the big picture. My statistics background is decent, but I have not gone much beyond t-tests and ANOVAs before, and so this week I also met with one of the research engineers to learn about the statistics she had ran previously on a similar study. It gave great insight to how I want to tell the story of this study.
This week we had our last summer immersion meeting and a farewell dinner. The dinner was wonderful, and it was a great way to end these seven weeks! When I get back to Ithaca, I will begin to write my paper for this class to put all my clinical experiences and research project together.
Also for this week I went to the NICU (neonatal intensive care unit) for two days to go on rounds with the residents and observe the treatment protocols for the babies under observation there. It was very interesting how technical and precise all the residents must be with regards to the medication administered to each baby - every volume and concentration must be carefully documented and increased/decreased in small increments to adjust each baby’s vitals at a gradual and safe pace. Many of the babies were premature, and as such they are more at risk for serious complications following birth. One baby was one of twins, and it had had a partially resected ileum. The post-operative course involved close monitoring for infection and keeping the baby on a ventilator until it showed better vital signs. The residents also said that they would be warming up the baby slowly – but they had to be very careful because if they warm up the baby too fast it may cause coagulation complications and brain reperfusion problems. A variety of instruments and devices were used to monitor and treat the babies, and there was a lot of information to keep track of for each patient. Although each baby requires different procedures and treatments, there were a few common treatments applied across several patients: phototherapy to combat hyperbilirubinemia, constant positive air pressure (CPAP) for breathing, incubation in highly controlled chambers, and total parenteral nutrition (TPN). One of the most interesting things about these baby patients is that they cannot communicate as adult patients do – they can only cry and that gives us minimal insight. Instead, doctors must rely exclusively on diagnostic measurements such as ECGs, stool samples, x-rays, feeding patterns, and increases in weight. From these readouts, physicians are able to diagnose and successfully treat the babies in the NICU.
I also attended more office procedures (i.e. scar removal/modification, botox injections, nipple reconstruction, steroid injections for wounds that are not healing properly, etc.) and I was able to observe several follow-up consults for patients who underwent surgeries in the first few weeks of my summer immersion experience. It was really great to see the follow-up patients so that I could get an idea of how well they were healing and what kind of rules/restrictions they had to deal with. For instance, the fleur de lis abdominoplasty patient is healing well, but she had to use drains for 2 weeks to remove excess fluid collecting in her abdomen as a result of the body’s healing processes. For her second post-op meeting with Dr. Grant, she was finally allowed to have them removed, which made her extremely happy. The C-section patient is also healing well, and her scar is barely visible now! I am impressed at how fast patients can heal, especially after learning how invasive these surgeries can be.
On that same note, I did see a surgery with Dr. Simmons, who works primarily with invasive breast cancer. I observed a breast resection and lymph node biopsy. What was interesting was that the lymph node tissue sample as sent to pathology, and we immediately got a response that the tissue was benign. This meant that the rest of the lymph nodes could remain. The breast resection was interesting, especially as it relates to my research project. The cancerous mass was removed, and then the edges around the mass, known as the "margins" were also removed for testing, in case the cancer had spread. This is exactly what the device is meant for, to test the margins for tissue stiffness (cancerous tissue is stiffer than healthy), so that tissue is not needlessly removed. All in all a very interesting surgery.
This was a very educational and exciting experience. I would like to thank everyone who put the time and effort to make this possible, as well as my mentor, Dr. Spector, for sponsoring me for this summer.
This week I was able to wrap up my summer immersion term with a trip to the cardiac thoracic department to see a triple coronary artery bypass, also called a CABG. This surgery was extremely different from any of the other surgeries I saw this summer and was a great opportunity to see a lot more technology used in the medicine field. I was able to see an echo preformed and the patient placed on bypass (the heart-lung machine). The patient had three clogged arteries so a vein was taken from the upper right thigh of the patient and divided into two sections to bypass two of the clogs, while the third clog was bypassed by using a mammary artery. It was very interesting to see how quickly and minimally invasively the PA was able to remove the vein from the thigh and prepare it for the bypass. During the surgery I was able to stand at the head of the patient and look down into the chest cavity as the surgeons worked. It was amazing to see the heart working in person. We have spent so many years now as biomedical engineers learning about the heart and all that it does, and then to get the chance to see it in action is just amazing. Additionally it was very impressive how quickly the surgeons were able to perform the bypass. The patient was only on the bypass machine for 32 minutes.
This week I was also able to take a tour of the biomechanics research facility at HSS. This will be very helpful if in the coming years I find I need certain equipment to perform my research.
What I feel I have gained most from summer immersion is motivation for the rest of my career. You can read statistics on how many people are effect, and how injuries affect patients lives over and over again from journal articles but it doesn’t really sink in until you get to experience firsthand these statistics in real life. My research in undergrad and graduate school has and will focus around the orthopedic field. Obviously, this field does not have the high life threatening problems as does the cardiac and cancer fields, so it is easy to lose motivation or feel your research will only help the super athletes. However, through seeing patients and observing surgeries this summer, I have begun to wrap my head around just how many people are plagued by orthopedic problems that have no solution other then total replacement, which only then lasts 10 years max. There is a real need for multiple solutions so that these people can live without pain every day of their lives. I am confident these past few weeks on summer immersion will stay with me the rest of my career and fuel my research.
Friday, July 30, 2010
This week has been focused mainly on finishing my research project. I am working on quantifying the binding of a single chain version of a monoclonal antibody. Thus far I have had trouble conjugating the single chain and this week I am attempting a new technique.
During my last week I attempted to block the binding of a fluorescently labeled monoclonal J591 antibody with the single chain version of J591. The experiments produced promising results however, they must be modified and repeated to verify that the single chain is binding and thus prevent the fluorescently labeled monoclonal antibody from binding to the cell surface PSMA.
As far as clinical work, I have wrapped up the summer with my physician in the area of urology. During the summer I watched in the office diagnostics as well as surgical procedures. The physician I worked with, Dr. Te, specializes in laser prostate surgeries. In the office he usually determines the extent to which there is blockage from the enlargement of a patients prostate or if the enlargement is related to malignant tumor growth.
I learned quite a bit about the stages and degree to which the enlargement of the prostate affects the quality of life of the patients treated by Dr. Te. In addition to the decisions that the doctor is required to make and the information used to guide those decisions.
After this summer I plan on continuing my work on the project that I was working on over the summer and keep my physician up to date with the information. I also hope to continue to collaborate with Dr. Te on future projects.
Thursday, July 29, 2010
I will most likely continue work on my Immersion term project after I leave Manhattan, as most of it can be done remotely. If I am lucky, the work may turn into a publication down the road and will also help keep me connected with physicians at the Weill Cornell Medical College.
Wednesday, July 28, 2010
In the E.R., I met up with Dr. Lemery, who gave me a tour of the various units that constituted the emergency room. We also discussed various pieces of technology he thought could be improved in the E.R., as well as finding ways to optimize patient flow in the E.R.. I was then paired with Dr. Heath, as senior resident, to shadow for most of the day. Most of the cases were fairly standard; bumps and bruises sustained through falls. However, I did meet a fairly chatty Nazi concentration camp survivor, who refused to believe a fall would do him in. Additionally, I saw a woman who presented with back pain that had all the signs I've come to recognize as a spinal stenosis in her cervical/thoracic spine. However, she was adamant the pain was related to an infection. I was struck by how multi-talented E.R. doctors have to be in terms of interacting with patients across various barriers (i.e physical and emotional state of the patient upon arrival, language) and having knowledge of all the various maladies they might encounter in the E.R..
This week, I spent some time in Dr. Stephen Doty's laboratory in HSS. Dr. Doty's lab specializes in the evaluation of bone, cartilage, and other connective tissue by means of histology and immunohistochemistry. A particular research interest of Dr. Doty's is to find a way to quantitatively evaluate histological samples. In Dr. Doty's laboratory, I spent some of my time familiarizing myself with various histological instruments, such as the microtome, and various common stains for these types of tissues, such as Alcian Blue, Picosirius Red for collagen, and the standard Hematoxcylin and Eosin. I also learned what the intervertebral disc and end plates of the vertebrae would look like under each of these stains. Dr. Doty is truly a master of histology, and I hope to use his expertise in my research at Cornell.
Most of the rest of this week focused on my research project. After extensive searching and refining, I finally narrowed down the 12 patients I could use for data, and began to compile as many demographics as possible. Already, there are some statistical differences in terms of pain pre- and post-op. Additionally, I have narrowed down 8 more patients that could be added, but may need to be called to gather additional data. I also began to write the abstract for SMISS, although it is becoming apparent that there may not be enough time for me to write this abstract or work on a paper for these findings. Dr. Hartl suggested that another fellow might collaborate with me while I am in Ithaca to get both these things done.
Looking ahead to the next week, I plan on getting back into the O.R. to see a few more cases, finish up what data collection I can, and learning how to use MRI and CT to look at Cobb angles in patients. Already, it has been quite a summer, and I look forward to wrapping up next week.
Tuesday, July 27, 2010
This past week I also met with my Ithaca PI’s collaborator here at Weill. Dr. Joseph Scandura works in the hematology and oncology departments, specializing in blood cancers like leukemia and lymphoma. He received his undergraduate training in electrical engineering and was surprisingly adroit when it came to engineering matters. He proposed a particularly elegant and novel way in which to implement PCR within channel-confined droplets. I hope to follow up his suggestion upon return to Ithaca as to my knowledge it represents a completely original solution to an important problem.
Also this week, I had the opportunity to shadow Dr. Bostrom, an orthopedic surgeon, for a day as he met with patients for follow-ups, infections, and for new visits. During this particular day, he was "triple booked" with 4 pages of patients he was supposed to visit within 10 hours, so it was a very hectic day. I was able to see a lot of different cases, though. Some patients were recovering from a knee or hip replacement very well, while others were having pain issues, and one had a horrible infection. Others were getting advice on whether they were a candidate for a total knee or hip replacement. Furthermore, some were doing very well post-op according to Dr. Bostrom, but the patient was unhappy with their abilities at this certain point in time. One of the highlights from my day with him was meeting a famous actress and patient of Dr. Bostrom. Because of his reputation, he has quite a few patients who are famous.
Also this week I shadowed Dr. Bostrom in the OR for an entire day. I saw a hip revision, a knee revision, and a total hip replacement. The second two surgeries I was actually allowed to scrub in on, and so I had a perfect view of the entire process! Seeing the total hip replacement up close was by far the coolest thing I have done on immersion term so far. I was so shocked at how fast the whole process was. Dr. Bostrom's part was done in about 45 minutes! He has to rotate the hip so that the joint pops out, saw off the femoral head, drill a hole into the cancellous bone of the femur, fit a post, drill the acetabular cup, hammer in the metal cup, snap on the plastic cup, pop the hip back in, then sew up. It was incredible to see it all in action and to see all of the drills and saws that are used in orthopedics.
This week I also finished analyzing the retrieved knee implants. The next step in my project will be running statistics on everything to reveal our findings. I will be meeting with one of the research engineers to discuss the best strategy for this analysis.
Monday, July 26, 2010
On Thursday, I observed a kidney transplant surgery (that I’ve been waiting for weeks). The recipient is a 14 yr old boy diagnosed with Focal Segmental Glomerulosclerosis (FSGS), a major cause of nephrotic syndrome in children and adolescents. He has an identical twin brother who had a transplant surgery last year. The patient suffers from chronic renal insufficiency at stage (CKD5), a progressive loss of renal function over a period of months or years. Patient’s mom, a 44 yr old healthy female, is the donor. Dr. Del Pizzo, who has vast experience in the laparoscopic and robotic treatment of kidney and adrenal tumors, kidney sparing surgery, and living kidney donation, successfully harvested the kidney. Single-incision laparoscopic kidney removal was performed, which offers minimal risk and quick recovery and allows the kidney to be taken out easily. Upon removal, the kidney was submerged in ice-cold saline solution, cleaned (blood and excess fat) and placed on the lower right of the patient’s abdomen and surgically connected to nearby blood vessels.
On Friday, Matt and I shadowed Dr. Sperling at the Emergency Department. I will be writing about my experience later next week since I would lie to go back to the ED and observe more cases.
Aside from shadowing in the ER, the rest of the week was more of the normal schedule of seeing patients with Dr. Rodeo, grand rounds for arthroscopy, and many orthopedic surgeries. I think one of my favorite things to do while here for the summer is to see patients with Dr. Rodeo. It is very interesting seeing firsthand how orthopedic problems affect so many people from the super athletes to the degenerative disease aged patients. It is also very touching to see how many younger patients, under the age of 20, have very serious orthopedic problems needing surgeries that will only delay the inevitable total knee replacement. Seeing these patients and what they must deal with on a day to day basis will help to motivate me the rest of my career and I really appreciate the opportunity.
In addition to this surgery, I spoke with an oncologist, Dr. Simmons, who specializes in removal of invasive breast cancer. This meeting was very informative, as I learned about cancer and talked with her a bit about my project, which hopefully will in the future be able to test cancerous tissue. I will be observing one of her surgeries next Wednesday, which will give me a different perspective of cancer-removal surgery.
The remainder of my week was spent on my project, testing the stiffness of different tissue, calibrating the device, and retesting. I am working on the analysis of this data, mostly analyzing stiffness differences in muscle and fat. Eventually this device could test different tissue (both diseased and healthy), but for my immersion project, I am simply doing a proof-of-concept on the device, to ensure that it works properly. So far I have been getting good results!
I wrote n draft, which includes some brief reasoning, methodology and some figure results.
This week I got to see the DaVinci surgical robot in action with Dr. Scherr in urology. Coming from an electrical engineering background the robotic system itself was quite impressive. It was clear to me that the size of the instruments and the magnification the device gives the surgeon allows for greater flexibility during the surgery. Though I wonder how difficult it is for the surgeon to control the robot during a delicate procedure; for example, how well can the surgeon control how much force they apply to their instruments while performing the procedure? Towards the end of the procedure while the surgeons were tying their final sutures I got the chance to actually see what the surgeons see through the console of the DaVinci system. Though I could not touch any of the controls on the console, from peering through the viewer of the console it was clear that the binocular vision that the system provides for the surgeon does give the surgeon a three dimensional impression of the environment where the tools are in the body. The only issue that I could see that the surgeons might have had during the procedure was that obtaining this view required that the endoscope that provided this view remained dry, which is difficult in the environment in which the endoscope must be placed to obtain the proper view of the surgical area.
To wrap up my project I am currently still working on using the simulation that I created this past week to work with real data from an MRI scan. Completing this is my goal for next week along with presenting what I find to the researchers that I have been working with over the summer and Dr. Gauthier.
Sunday, July 25, 2010
Besides, I attended a seminar on cancer stem cell given by EMD company. Since I have been working on colon cancer stem cells this summer, I found tremedous guidance from this seminar which pointed out three main directions within cancer stem cell research: 1. single cell study;2. How niche contributes to CSC. 3. response of CSC to chemotherapy.
Lastly, I also attended my first lab meeting here. One of labmates gave a wonderful talk on her work in the past few months. Previously, by using aCGH array, she identified increased copy of certain region in certain cancer cell lines which turned out to be a cluster of microRNA. microRNA is a hairpin RNA with a length of ~20bp. By binding to 3'UTR of mRNA in mamalians cells, they can downregulate target gene expression. Since increased copy number is associated with higher expression of certain microRNA which led to downregulated target gene expression, she is seeking to study if the effect can be reversed by using specific antisense RNA which binds to microRNA.
Overall, this week I feel fully immersed in research study from which I learnt new technique as well as new knowledge.
Working on my research, I continued to help my mentor prepare for a clinical trail of the use of the new GE t1 mapping tool in cardiac amyloidosis. This week we got the mapping software from GE and I worked to install it, learn it, and run it on some cases. I also ran a few scans using phantoms with known t1 values, to evaluate the consistency of the reconstruction tool. It works fairly well, but does have some variability. I will cover this in my final report for the class. In addition, I went to pathology this week to see slides from a positive amyloid case, that we had done an MRI on, and then the patient got a biopsy. It was really neat to see the amyloid under the microscope, and how it affects the myocardium.
A highlight of the week was to attend grand rounds on an interesting subject: fibrosis as a cause of organ failure. There I learnt that doctors think (but aren´t sure) that collagen produced by fibroblasts that come from endothelial cells through an epithelial-mesenchymal transition cause the fibrosis that damages organs. To me it seems very clear that this is a wound healing response and that stopping it might help the body to regenerate a little bit better but the underlying cause of allograft rejection is still an immune response which is what doctors such focus on controlling.
Saturday, July 24, 2010
The surgery that called my attention was a lumbar posterior fusion on a 46 years old patient. This surgery was performed because the previous surgery did not fused and the x-ray showed that it was not healing Dr. Farmer took the screws that were loose and the procedure had to used several x-rays to determined if the new screws were placed on the write position.
Also, I was able to work with Dr. Abjerson and Hani. This lab is interested on the development of a new strategy for a better integration of bone-implant interface. This consists in the use of a chemical surface treatment results in a self-assembled monolayer of phosphonate molecules (SAMP). At the same time, I worked a subproject helping determined the best position of infrared cameras to determine the displacement of a spine due to constant load.
Friday, July 23, 2010
This week I have been spending the majority of my time on my research project. I am working on quantifying the internalization of the J591 antibody in LnCap cells, a prostate cancer cell line. The antibody I am testing is actually a single chain version of the monoclonal antibody. I have been having some issues with labeling the antibody using the amines, this is due to the size of the single chain. There are a lot fewer amines for the fluorophore to conjugate to. However, the antibody has a his-tag located at the n-terminal end of the protein that could be exploited to label the antibody.
We are now attempting to label the single chain using a new conjugation method that binds the fluorophore to the his-tag instead of the amines. We hope that this will allow for enough conjugation to reduce the noise we are seeing with the current method. In addition, we hope that the single chain will have results comparable to what we are seeing with the monoclonal antibody staining. Thus far we have been unsuccessful in comparing the two due to the poor conjugation we are seeing with the single chain.
The significance of this work is in the unique targeting and production of a targeting agent. The single chain will be easier to make than the monoclonal antibody and could possibly allow for mass production of a targeting agent for prostate cancer therapies.
Thursday, July 22, 2010
I was able to observe cardiothoracic surgery with Dr. Leonard Girardi attending. The operation was an aortic valve replacement on a man in his 50s. While waiting outside the OR, I met two sales representatives from Edwards Lifesciences, the company that manufactures the heart valve replacements. They were on hand to field questions posed by the surgeon on the proper selection of valve replacement. If the chosen valve is too small, the pressure gradient across the valve will be too great, leading to device fatigue and premature failure. One of the sales reps. explained that the goal is to achieve a gradient as close to that associated with the natural valve as possible. The sales reps showed me a chart that indexed the cross sectional area of the valve against the BMI of the patient. This convenient chart was color coded (green corresponding to a safe match, yellow to a satisfactory match, red to a severe mismatch). Larger patients need correspondingly larger valves. Given that the pressure inside a channel exhibits a fourth power dependence on channel diameter, even minute increases in the diameter of a valve can result in substantially lower pressures and hence less likelihood of failure. The sales reps. were very knowledgeable and were able to provide a play-by-play of what was occurring during the surgery. I learned many things from my first time in the OR. For instance, I knew that the surgeons siphoned off blood from the thoracic cavity so as to facilitate surgery but I did not know that the patient’s blood was stored and then reintroduced afterward. I assumed that banked blood was used and that the patient’s blood was disposed of for reasons of contamination. One of the sales reps. pointed out the cell saver device that stored the patient’s blood and then reintroduced it. Also, they pointed out that to prevent clogging of the tubes that carry the blood to the cell saver, a blood-thinning anticoagulant agent (heparin) is administered. Upon completion of the surgery, the effects of the heparin had to be countered. Room temperature was raised when the surgery was over and the surgeons were attempting to restart the patient’s heart. I was impressed with the size of the staff on hand – nearly 20 people. The atmosphere was like that of mission control with the surgeons calling out for readings or barking out orders and the support staff flatly intoning dial readings or confirming compliance with the order.
Later in the week I was able to spend time in the emergency room (ER). Dr. Dean Straff gave me a tour. Afterward, I followed one of the senior residents on rounds and saw several cases. Dr. Straff explained that the ER sees everything from the mundane to the unprecedented. Anyone who shows up at the ER will be seen, regardless of how minor their complaint really is. Upon arrival, patients are triaged – the severity of each case is assessed and the patient is relocated accordingly. The ER is organized into three areas: A, B, C bays. Section A is nearest the ambulance drop off so usually houses the most severe cases. Among the cases I observed, several stood out.
1. An elderly man who had been the victim of a brutal physical assault late last year and suffered a stroke soon afterward was admitted from his nursing home due to a feeding tube coming loose and an infection taking hold. The gentleman was in a vegetative-like state, moving his eyes and moaning in response to discomfort but otherwise unable to communicate. X-rays of his chest looked foggy so pneumonia was discerned and antibiotics prescribed.
2. Girl in her mid-20s with a family history of heart disorders (father had heart attack at young age, brother had heart defect, etc.) was admitted complaining of severe chest pains, the intensity of which changed with position. The senior resident was inclined to believe this was pericarditis, an inflammation of the sac that surrounds the heart, which is caused by a viral infection. The girl remembered having a cold a month earlier. Ordering a CT scan was one possible way to confirm this, but the senior resident cautioned against it unless it proved absolutely necessary, as the radiation dose is equivalent to about 200 x-rays – an amount inadvisable to be administered to a young woman due to the sensitive nature of the breasts and ovaries to radiation.
3. A middle-aged man presented with an abscess on his ankle. He had earlier broken his ankle and had it mended but had developed an infection. The senior resident lanced the abscess and drained it of pus, taking a culture sample for analysis. She explained that if the situation were dire, the patient would be put directly put on a general antibiotic, but because the situation was not life-threatening, they had the luxury of sending a sample to the lab for analysis to identify the specific bacteria so as to prescribe a more narrowly-focused antibiotic.
Also, a new mobile computer system was unveiled to the ER staff. This cart-mounted computer terminal was touted as being able to obtain digital signatures on consent forms and discharge papers from bedridden patients. The mobile terminal also featured an RFID reader which granted access upon swiping an ID badge, saving precious seconds that might otherwise be spent keying in a password or trying to recall a password from memory. A senior staff member at the ER was absolutely beside himself with excitement, going on at great length as to how this represented the paradigm that all emergency rooms in the nation were going to emulate in the coming years. He claimed it would free up very expensive hospital beds and result in faster turn-around time, more important than ever with cutbacks to government-supported insurance programs like Medicare and Medicaid.
The electronics needed for my research project finally arrived. I was able to verify the operation of the load cells. One observation was that the load cells exhibited a non-zero voltage output in their non-stressed state. So, I may have to account for this DC offset in the final design of the device.
My other project involves interfacing a microcontroller to a commercial sleep monitor known as a Zeo Personal Sleep Coach. The device isn’t intended as a research tool, but owing to its many features and relatively low cost, it is ideal for use in clinical studies of long duration outside the lab, i.e. at a person’s home. As the device is intended to operate as a consumer device, it isn’t terribly amenable to alteration. Consequently, I spent a good amount of time exchanging emails with technical support from the company.
Lastly, I was given a Zeo of my own to explore. The Zeo consists of a headband with a sensor that monitors brain wave activity and streams sleep stage data wirelessly to a base station for storage and display. Data can be uploaded to the company website for analysis.