BIDMC News and Notes
3/19/2010 (2:50:55pm)Tags: noneComments: (0)
They may not be pioneers in the traditional sense, but Drs. Howard Bleich and Warner Slack certainly are trailblazers in the world of clinical computing.
Forty years ago the two doctors teamed up with other Harvard faculty to give birth to clinical computing. The result is the highly advanced medical records system in place at Beth Israel Deaconess Medical Center and Brigham and Women's Hospital. The applications that connected the two hospitals served as the prototypes for multiple commercial medical computing products, including those offered by Meditech, Epic and several other companies.
"Howard and Warner are giants in the field of clinical informatics," says Charles Safran, the division chief of clinical informatics at BIDMC. "So much of what we take for granted today was pioneered by these two men and their many colleagues here at BIDMC. Over the past 40 years, we have had 19 physicians and two nurses from six countries train as fellows within our division and today they are informatics leaders at Harvard and within their institutions and their countries."
The Division of Clinical Informatics was among the first academic divisions in the world to concentrate on the use of computers for patient care, teaching, and medical research. The goals have been to improve the quality and reduce the cost of medical care, to enhance the quality of medical education, to improve the relationship between doctor and patient, and to explore innovative approaches to research through computing.
Beginning in 1976, the faculty and staff designed, developed, implemented and studied hospital-wide, integrated computing systems for doctors, other clinicians, and students that would give the results of diagnostic studies immediately upon request; offer access to the biomedical literature with PaperChase (the first program of its kind, which in turn gave rise to a new field of literature searching and spawned numerous derivative programs); offer advice, consultation, alerts and reminders; assist with communication by electronic mail (with the Division's home-grown system, which was the first e-mail to be installed in a clinical facility); assist with order entry; and assist in the day-to-day practice of medicine, both for inpatient and ambulatory care.
"These products help in the care of millions of patients around the world," said Mark Zeidel, MD, Chief of BIDMC's Department of Medicine. "Paper Chase, which for the first time permitted physicians to search the medical literature, was the forerunner to PubMed, which we all use regularly. It is fair to say as well that UpToDate would not be what it is today had its founders not had the opportunity to interface constantly with the Division, its faculty and its graduates."
3/19/2010 (2:39:40pm)Tags: Red Sox sports medicineComments: (0)
Perhaps you subscribe to the opinion that the formal announcement of Nomar Garciaparra's retirement after signing a one-day contract with the Red Sox involved a bit of revisionist history. Well c'mon, what did you expect? Haven't we all had a bad break-up somewhere in our past and wanted a do-over? Not that we hoped to get back together, it was just uglier than it needed to be. (In my case, I even felt oddly guilty when I heard her cat ran away...not that wishes can really make things happen).
Nomar's 2004 exit was a bad break-up followed by a breakdown. Actually, the breakdown began much earlier. We just didn't know it then.
"Pro baseball may not be a collision sport but it is a grueling sport," says Dr. Arun Ramappa, Chief of Sports Medicine in the Department of Orthopedic Surgery at Beth Israel Deaconess Medical Center. "The regular season is one hundred and sixty two games not to mention spring training and post-season. And the skills necessary to play - pitching, batting and throwing - place enormous stresses on the body."
Garciaparra seemed to be bearing up fairly well under the physical and mental stress. He was a unanimous selection as Rookie of the Year in '97 and a second place finish in MVP balloting in '98. Sure, he had his share of bumps and bruises before September 25, 1999, but on that night Nomar was hit on the wrist by a pitch thrown by Baltimore's Al Reyes.
The injury didn't seem all that significant at the time or even the next season - he won American League batting titles in '99 and 2000 - but in Spring Training 2001 the wrist ballooned, rest and rehab proved unsuccessful and surgery ended his season. Even though he returned to All-Star form, his best seasons were behind him.
"If a lawyer has wrist surgery, it's not going to affect their work performance. Almost as good as new is probably more than good enough," says Dr. Ramappa. "That's not necessarily the case for a professional baseball player. Especially when the difference between being a great hitter and a good hitter is very small to begin with."
I think it's fair to say that when the Sox attempted to acquire A-Rod after the 2003 season their relationship with Nomar went south. So did Garciaparra's injuries. He had Achilles' problems that spring and after a trade to the Cubs tore his groin muscle in April of '05. He bounced back with an All-Star season for the Dodgers the next year, but spent his last two seasons as a part-time player dealing with a variety of injuries and ailments, including chronic exertional compartment syndrome, a condition that limited his muscles ability to recover quickly from activity.
"I know I've said this before but it bears repeating. Every individual is different. Our bodies react differently to wear and tear. Some people are born with steel-belted racing tires. Some are born with retreads and more prone to blowouts. The Cal Ripkens of the baseball world are rarities," he says.
Given what we've come to learn about the use of performance enhancing drugs in baseball, there are some who point to Nomar's relatively rapid decline as evidence of steroid use. Personally, I was witness to a few of his off-season workouts. If I worked that hard in the gym, I'd pose shirtless if Sports Illustrated asked.
There's no doubt that Nomar's occupation accelerated his physical decline. Carpenters, laborers, and others whose jobs involve repetitive exertion are also at increased risk. We can't stop the clock, but we can slow down the process.
"Keep your body tuned up. Cardio work is important but so is strength training. You'll build muscle mass and bone mass," advises Dr. Ramappa. "Working on your core strength rather than a beach body is especially helpful. And you want to include stretching. A lot of back issues and other common injuries can be prevented by investing even a little bit of time in flexibility exercises."
So whether you are interested in avoiding breakdowns or repairing bad break-ups, try applying a little flexibility. You might be pleasantly surprised at the result.
Above content provided by Beth Israel Deaconess Medical Center. For advice about your medical care, consult your doctor.
3/8/2010 (10:44:45am)Tags: nursing Boston CollegeComments: (0)
Boston College Magazine followed a number of student nurses as they shifted from the classroom to the patient room at BIDMC.
Tag along yourself here.
3/5/2010 (10:19:25am)Tags: research sepsisComments: (0)
Inflammation is at the root of most serious complications occurring after both infection and injury. But while the molecular course of events that leads from microbial infections to the inflammatory condition called sepsis is fairly well understood, it is far less clear how and why physical injury can result in a similarly dangerous inflammatory response.
Now a study led by investigators at BIDMC suggests that mitochondria - the body's cellular "power plants" -- are released into the bloodstream following physical injury. And because mitochondria closely resemble the bacteria from which they originated, they appear to elicit a sepsis-like immune response, changing from a vital source of cellular injury to a dangerous "enemy within."
Appearing in the journal Nature, the findings could eventually lead to new strategies in the management of trauma as well as to the development of new tests to help clinicians discriminate between infective and non-infective inflammation.
"The body's vital organs can become dysfunctional when traumatic injury triggers the Systemic Inflammatory Response Syndrome, or SIRS," explains senior author Carl J. Hauser, MD, a trauma and critical care surgery specialist at BIDMC and Visiting Professor of Surgery at Harvard Medical School. "Trauma kills 5 to 10 million people worldwide per year and among U.S. individuals under age 35, trauma accounts for more deaths than all other illnesses combined. Inflammatory complications are directly responsible for about one-third of those deaths."
For more, click here.
3/3/2010 (10:53:13am)Tags: lincRNA genomics researchComments: (0)
Once considered "genomic junk", a class of RNA genes known as large intervening non-coding RNAs or "lincRNAs," are now considered "genetic air traffic controllers." Playing a key role in helping to raise understanding the roles of these molecules in many biological processes - including stem cell pluripotency, cell cycle regulation, and the innate immune response - is the work of a scientific team from BIDMC and the Broad Institute.
But even as one question was being answered, another was close on its heels: What, exactly, were these mysterious molecules doing?
They now appear to have found an important clue. Described in the July 14 issue of the Proceedings of the National Academy of Sciences (PNAS) the team shows that lincRNAs have a global role in genome regulation, ferrying proteins to assist their regulation at specific regions of the genome.
"I like to think of them as genetic air traffic controllers," explains co-senior author John Rinn, PhD, a Harvard Medical School Assistant Professor of Pathology at BIDMC and Associate Member of the Broad Institute. "It has long been a mystery as to how widely expressed proteins shape the fate of cells. How does the same protein know to regulate one genomic location in a brain cell and regulate a different genomic region in a liver cell? Our study suggests that in the same way that air traffic controllers organize planes in the air, lincRNAs may be organizing key chromatin complexes in the cell."
Rinn is one of 16 young investigators who will present work at BIDMC's Research Day 2010, March 5, in Sherman Auditorium.
Inspired by a lincRNA called HOTAIR -- which is known to bind key chromatin modifier proteins and to assist in getting these proteins to the proper location in the genome - the researchers hypothesized that other lincRNA molecules might be playing similar roles.
"DNA wraps around partner proteins to form a structure called chromatin, which affects which genes are ‘turned on' and which are ‘turned off'," explains first author Ahmad Khalil, PhD, a scientist in the Department of Pathology at BIDMC and the Broad Institute. "Chromatin does this through a process of compaction; by determining which areas to compact and which to leave open, chromatin successfully determines which genes are accessible for transcription."
But he adds, it has been a mystery as to how this chromatin structure is so precisely targeted by specific enzymes - and not others.
"By utilizing a technology known as RIP-Chip we were able to examine RNA-protein interaction on a large scale and determine which lincRNAs are associated with each enzyme we examined," he adds. To analyze this tremendous amount of data, coauthor Mitchell Guttman, PhD, a bioinformatician at BIDMC and the Broad Institute, used a mathematical algorithm that identified which lincRNAs are bound by chromatin-modifying enzymes and which are not.
"This analysis revealed that 20 to 30 percent of lincRNAs are bound by three distinct chromatin-modifying complexes," adds Khalil. "By depleting several of these lincRNAs from cells, we were able to show a significant overlap between the genes which become affected by the depletion of lincRNAs and the depletion of the enzymes. This provided us with the evidence that these proteins work together with lincRNAs to target specific regions of the genome."
Standard "textbook" genes encode RNAs that are translated into proteins, and mammalian genomes contain about 20,000 such protein-coding genes. Some genes, however, encode functional RNAs that are never translated into proteins. These include a handful of classical examples known for decades and some recently discovered classes of tiny RNAs, such as microRNAs. By contrast, lincRNAs are thousands of bases long. Because only about 10 examples of functional RNAs were previously identified, they seemed more like genomic oddities than key players. With these latest findings, which also uncovered an additional 1,500 lincRNAs, it's clear these RNA molecules are no mere messengers - they have demonstrated that they can and do play a leading role.
"Much work still remains to be done but we could one day envision utilizing RNA to guide personalized stem cells to specific cell fates to restore diseased and degenerative disease tissues," notes Rinn.
3/2/2010 (12:45:43pm)Tags: peripheral artery disease CardioVascular InstituteComments: (0)
Walking is beneficial for lots of reasons, and one of its key benefits is its role in protecting our hearts. Zoltan Arany, MD, PhD, a scientist in BIDMC's Cardiovascular Research Institute, investigates the biological mechanisms of cardiac health and disease.
His laboratory recently published a study in the medical journal Proceedings of the National Academy of Sciences (PNAS) describing the importance of a gene called PGC-1alpha, which was found to play a key role in heart health. Here, Dr. Arany talks about his research - and the benefits of walking.
Arany is one of 16 young investigators who will present work at BIDMC's Research Day 2010, March 5, in Sherman Auditorium.
Your study looked at a condition called P.A.D. Can you explain what that is?
P.A.D. stands for peripheral artery disease, which is a condition that develops when the arteries in the legs become clogged with plaque deposits and result in reduced blood flow to the limbs. This results in leg pain and disability. P.A.D. affects 8 million individuals in the U.S. and is the leading cause of limb amputations.
How is P.A.D. related to cardiac health?
P.A.D. is a warning sign that fatty deposits in the arteries may also be reducing blood flow to a person's heart or brain, putting him or her at risk for a heart attack or stroke.
What is angiogenesis and what role does it play in this process?
Angiogenesis is the name for a biological process in which new blood vessels grow and develop. Our bodies have a terrific built-in "alarm" system that indicates when our blood circulation is impaired- when, for example, arteries are clogged with plaque. This "alarm" can trigger the angiogenic process whenever an injury or artery blockage has left normal tissue starved for blood.
What did your latest research find?
Last year, I led a research team that discovered that a gene called PGC-1alpha contributed to "turning on" the angiogenic process. We found that this gene can sense when levels of oxygen and nutrients are dangerously low, as would occur when tissue is damaged following cardiac disease or in P.A.D. In response, PGC-1 alpha then activates the process that leads to the formation of new blood vessels.
With the current study, we wanted to find out if exercise could activate this gene. We did this by studying two groups of mice in cages equipped with electronically monitored running wheels; one group of mice had the gene, the other didn't. Follow-up tests found that the mice that were lacking the PGC-1alpha gene failed to grow new blood vessels even though they exercised. The other group of mice showed robust growth.
So, with this research we have shown that this protein can single-handedly transform muscle to be capable of greater endurance and increase the blood vessel content of that muscle. Being able to increase blood vessel density could help wound healing and even prevent amputations in millions of patients with diabetes and vascular disease of the limbs, including P.A.D.
What advice would you give to patients?
Exercise remains one of the most effective interventions for a number of chronic diseases, including obesity, diabetes, atherosclerosis and neurodegenerative diseases. P.A.D. is a leading cause of morbidity and the most common cause of limb amputation in the U.S. and yet even the best medical therapy available is less effective than simply taking a daily walk. So, my advice is: Keep moving!
3/1/2010 (12:28:19pm)Tags: dinosaurs birds evolution Comments: (0)
Ancient protein dating back 80 million years to the Cretaceous geologic period has been preserved in bone fragments and soft tissues of a hadrosaur, or duck-billed dinosaur, according to a recent study led by scientists at BIDMC and North Carolina State University (NCSU).
The findings, published in the May 1, 2009, issue of Science, support earlier results from analyses suggesting that collagen protein survived in the bones of a well preserved Tyrannosaurus rex, and offer robust new evidence supporting previous conclusions that birds and dinosaurs are evolutionarily related.
In April 2007 John Asara, PhD, Director of the Mass Spectrometry Core at BIDMC, together with NCSU paleontologist Mary Schweitzer, PhD, published two papers in Science describing their discovery that collagen extracted from bone fragments of a 68-million-year-old T. rex closely matched the amino acid sequences of modern day chickens. Not surprisingly, the widely publicized findings created a great deal of controversy.
Asara is one of 16 young investigators who will present work at BIDMC's Research Day 2010, March 5, in Sherman Auditorium.
"With this new paper, we hoped to show that our T. rex discovery was not a unique occurrence," notes Asara, who is also an Instructor in Pathology at Harvard Medical School. "This is the second dinosaur species we've examined and helps verify that our first discovery was not just a one-hit wonder. Our current study was the collaborative effort of a number of independent laboratories, whose findings collectively add up to a robust conclusion."
At the heart of the controversy is the idea that ancient protein can exist at all. When an animal dies, protein immediately begins to degrade and, in the case of fossils, is slowly replaced by mineral, a substitution process assumed to be complete by 1 million years. But with this latest evidence, it appears that some proteins do indeed have real staying power.
"We wound up identifying nearly double the number of amino acids we recovered in the T. rex study," says Asara. "The sequences displayed high spectral quality and the interpretations were of high confidence."
The two scientists had decided to collaborate again after Schweitzer and paleontologist Jack Horner of Montana State University's Museum of the Rockies recovered the 80-million-year-old Brachylophosaurus canadensis femur bone in the summer of 2007 and observed that it appeared to be even better preserved than the original T. rex fossil.
Schweitzer's initial laboratory analyses confirmed this observation: After being subjected to demineralization, the B. canadensis bone fragments showed marked preservation of original tissues and molecules, with microstructures resembling soft, transparent vessels, cells and fibrous matrix - even though the fossil was much older than the T. rex sample.
"Deep burial in sandstone seems to favor exceptional preservation," notes Schweitzer, explaining that this fossil was found under approximately seven meters of sandstone in the Judith River Formation, in parts of what is now Eastern Montana.
Chemical extractions of bone and vessel were subsequently sent to the laboratories of BIDMC scientists Lewis Cantley, PhD, and Raghu Kalluri, PhD, where immunoblots and immunochemistry analyses were conducted to determine the presence of collagen protein in the samples.
"Having been a part of the T. rex study, I was curious to be part of this investigation as well," explains Cantley, Chief of the Division of Signal Transduction at BIDMC. "In view of the skepticism about the original findings, it was important to demonstrate that our findings in T. rex could be verified in another dinosaur and in other laboratories."
The results confirmed the existence of protein. "Because I am a collagen biochemist, our lab was contacted to perform an independent analysis of this new bone find," explains Kalluri, who is Chief of the Division of Matrix Biology at BIDMC. "We isolated the proteins - collagen, laminin and elastin - from the bone, and also extracted bone cells and blood vessels from this sample. Our findings demonstrated that it did contain basement membrane matrix."
In addition, In situ mass spectrometry studies conducted at Montana State University by Recep Avci and Zhiyong Suo independently verified amino acids in dinosaur tissues, including the collagen signature amino acid, hydroxylated proline.
From there, using a combination of two mass spectrometry technologies - linear ion trap and hybrid linear ion trap/orbitrap - Asara was able to improve upon the techniques he had used in analyzing both the T. rex specimen and specimens from bones of other prehistoric animals including a 300,000-year-old mammoth and mastodon.
At the beginning of the study, Asara explains, his lab used an ion trap mass spectrometer, which captures and holds peptides through time so that after the collected peptides are measured for mass they are isolated and fragmented to reveal their amino acid sequence. Then, while the study was in progress, his lab acquired a high-resolution and highly mass-accurate Thermo Scientific LTQ Orbitrap XL mass spectrometer, which was used during the second half of the analysis.
"Because it is capable of sub 2 ppm mass accuracy, the Orbitrap allowed us to make more confident sequence calls than we did in the T. rex study," Asara explains. "For example, the mass difference between a hydroxyproline amino acid residue [which is plentiful in collagen] and a leucine or isoleucine residue is only 0.0364 Da. Although this very small measurement proved to be an obstacle for the ion trap, it was not a problem for the Orbitrap." Material for mass spectrometry sequence analysis was also sent to the lab of William Lane at Harvard University and mass spectrometry sequence data were independently verified by John Cottrell, PhD, at Matrix Science in London, UK.
The end result was a total of eight collagen peptides and 149 amino acids from four different samples, sequences that held up when multiple validation steps were performed, including comparisons with synthetic peptides using a spectral comparison algorithm and statistical evaluation.
In the final portion of the study, coauthor Chris Organ, PhD, a Postdoctoral Fellow in the Department of Organismic and Evolutionary Biology at Harvard University, conducted a rigorous phylogenetic analysis of the identified sequences to determine B. canadensis' place within the evolutionary tree of animals. The B. canadensis collagen sequence data were compared to a database of collagen sequence data from 21 species of living animals and sequences from two other fossils, mastodon and T. rex. The results placed B. canadensis on the same family-tree branch with T. rex, in the same group as chicken and ostrich, and more distantly, to alligator and lizard.
"The phylogenetic analysis yielded clear results, but the placement of the extinct dinosaurs still rests on a limited amount of sequence data," notes Organ. "There is not enough sequence data to correctly parse out the relationships within Dinosauria [the group containing B. canadensis, T. rex and the two birds] but the group as a whole is well supported by the analysis, which is consistent with studies based on morphology."
Ultimately, notes Asara, "We were able to achieve these results, in part, because the mass spectrometry systems that our lab has set up for cancer research are capable of a similar concentration range - low to sub femtomole -- needed for ancient fossil protein sequencing. We hope to meet with similar success when it comes to identifying novel signaling proteins from cancerous tissues."
This study was funded, in part, through grants from the National Science Foundation, the David and Lucile Packard Foundation, the Merck Postdoctoral Science Research Fellowship, the National Institutes of Health and the Taplin Funds for Discovery, Harvard Medical School.
In addition to Asara and Schweitzer, coauthors include BIDMC investigators Lewis Cantley, Raghu Kalluri, Lisa Freimark, Valerie Lebleu, and Michael Duncan II; Wenxia Zheng of North Carolina State University; Chris Organ, John Neveu and William Lane of Harvard University; Recep Avci, and Zhiyong Suo of Montana State University; John Horner of the Museum of the Rockies (MT); Matthew Vander Heiden of the Dana-Farber Cancer Institute; and John Cottrell of Matrix Science, London, UK.
3/1/2010 (11:24:33am)Tags: research sepsisComments: (0)
"It's a devastating runaway infection." That's how Samir Parikh, MD, describes sepsis, a deadly disease that spreads swiftly through the bloodstream, often spurred on by post-surgical infections or complications of pneumonia. The widespread condition ranks among the top 10 causes of mortality in U.S. adults and is estimated to cost the health care system more than $16 billion a year.
Parikh is one of 16 young investigators who will present work at BIDMC's Research Day 2010, March 5, in Sherman Auditorium.
As a nephrologist who has witnessed the damage sepsis can cause in patients' kidneys, Parikh's research interests have focused on uncovering the cellular mechanisms responsible for the disease's cascading and devastating effects, which are triggered by rampant inflammatory responses in blood vessels throughout the body. Its destructive path through the bloodstream can result in vascular leakage, shock, multi-organ failure, and ultimately, death.
"Despite the armament of antibiotics available, these are not sufficient to combat the systemic complications people develop with sepsis," explains Parikh. "Antibiotics are critical, but we also have to fix inflammation of vessels and organs in the body, the loss of blood pressure referred to as septic shock, and the leakage of fluid out of vessels."
If the circulatory system is the highway on which sepsis travels, endothelial cells, which line the interior of blood vessels, are the pavement. Research originally begun by Parikh while a member of Vikas Sukhatme's laboratory has revealed that a molecular pathway within endothelial cells-the angiopoietin/Tie-2 system-is implicated in vascular inflammation and may be a potential marker and mediator of sepsis.
This past fall, Parikh's laboratory received a two-year grant from the National Heart, Lung, and Blood Institute, part of the American Recovery and Reinvestment Act (ARRA) funding, to enable his lab to continue this line of investigation.
"Our data has shown that when the angiopoietin/Tie2 pathway is activated, blood vessels do not leak; conversely, when the pathway is disrupted, the vascular leakage that is a hallmark of sepsis returns," he explains.
Parikh will use the ARRA funding to develop a transgenic mouse model that will enable his research team to activate and control the angiopoietin/Tie-2 pathway. Moreover, the investigators will be able to turn on the transgene in a targeted environment, such as the liver or lungs, to isolate and study angiopoietins' effect on one organ or cell at a time.
"This mouse model is an achievable project that will not only be useful for our questions in the study of sepsis, inflammation, and vascular leakage, but will also be a valuable tool for other researchers," he notes.
To learn more about research efforts in nephrology, click here.
2/26/2010 (3:14:02pm)Tags: breast cancer cancerComments: (0)
As a patient and then a volunteer Carol Mayer thought that BIDMC could use a specialty shop that would cater to cancer patients coming in for chemotherapy treatment. Ten years ago, Mayer and her husband Bob donated the money to open Windows of Hope. After a decade, the store continues to supply cancer patients with a variety of products and services.
Windows of Hope is located on the 9th floor of the Carl J. Shapiro Clinical Center across from the Division of Hematology/Oncology. Many patients and their family members frequent the shop, which offers many products and services they will need in one convenient location.
"Windows of Hope is amazing!" said Kit Lemaire, a former patient.
The warm and inviting atmosphere is due to the employees and volunteers of the shop including the shop's manager, Linda Myers, and the sales coordinator, Terri Cohen.
"Linda and Terri are also amazing," Lemaire said. "Without them I wouldn't have made it through my treatments." Lemaire was a patient at BIDMC for breast cancer, but will stop in to say hello to her friends in Windows of Hope if she is in the area. They always went above and beyond to be there for Lemaire. She was so glad that they made time for her even when they were not open. If she needed something, they would stay late with no problem.
Carol Mayer said, "Linda and Terri are my gifts from Heaven."
They are both very helpful and empathetic to the patients. Myers and Cohen are experts at helping patients try on hats, head wraps and wigs. They have over 100 wigs in stock, but it only takes a short time to special order one.
"This is the best job," Myers said.
2/26/2010 (2:41:15pm)Tags: Red Sox men's healthComments: (0)
BIDMC primary care physician Jacques Carter says baseball players have the right idea in mind when then tone the bodies as well as the batting, pitching and fielding skills in the spring,
While numbers like GDP( ground into double play), ERA (earned run average) and WHIP (walks and hits per innings pitched) are important, Carter says you shouldn't ignore others like BP (blood pressure and HDL (good cholestrol).
For more on his interview with Gary Gillis, click here.
