Patients with chronic obstructive pulmonary disease (COPD) may gain better control over their breathing and breathe more efficiently by using their breath to play a computer game, according to new research.

“COPD is a double-edged sword: the incapacitating lung condition can cause such serious shortness of breath that every-day physical activity, such as walking a flight of stairs, becomes unduly burdensome-and yet one of the few effective symptomatic treatments for COPD is the very thing that its victims dread most: exercise,” said leading researcher Eileen G. Collins, Ph.D., of the Edward Hines Jr. VA Hospital in Hines, Illinois and UIC. “This computerized program is still in the research stages, but shows promise for future use in pulmonary rehabilitation programs.”

The results of this randomized, controlled study appeared in the April 15 issue of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

COPD patients with the greatest disability are also those most likely to be unable to exercise long enough to reap the benefits rehabilitation can offer them. “One of the key mechanisms of shortness of breath and exercise impairment in these patients,” Dr. Collins said, “is their inability to fully exhale air when active.” This phenomenon causes trapping of air in the lungs-i.e., dynamic hyperinflation-and diminishes the patient’s breathing efficiency.

Dr. Collins and colleagues designed a randomized, controlled trial, the first of its kind, to test whether this computer program could decrease the extent of air trapping during exercise and thus improve the results of rehabilitation in COPD patients. “Our primary goal was to determine if patients with COPD would achieve longer exercise duration if they were engaged in ventilation feedback, in addition to the regular exercise program over either ventilation feedback or exercise alone,” said Dr. Collins.

A total of 64 patients were randomized to three groups- exercise alone, exercise plus ventilation feedback (VF) or VF alone. VF patients had their breathing monitored by a computer program which provided them with real-time biofeedback and set individualized goals, presented graphically on a screen in front of them. Patients could see their current speed and depth of breathing in relation to the set goal, encouraging them to inhale more slowly and exhale more completely in order to achieve the goal.

At baseline, the groups all performed similarly in exercise tolerance tests. Comparing all the groups, those that underwent a regimen of exercise and ventilation feedback showed significant improvements in exercise duration, and those who underwent exercise alone fared much better than those who only received ventilation feedback. Because of the multiple comparisons between groups, the exercise-plus-ventilation feedback group did not attain statistically significant improvements over the exercise-only group, but the results indicated a strong trend in that direction. Exercise-induced hyperinflation was also reduced in patients randomized to exercise-plus-ventilation feedback over either program by itself. Duration of exercise tolerance in the exercise-plus-ventilation feedback group also showed a significant trend toward improvement.

If patients can be taught to translate these breathing techniques from the computer game to activities of daily living, they could potentially greatly improve their quality of life. “We are conducting a follow-up clinical trial to compare computerized breathing feedback with other unique methods of pulmonary rehabilitation,” said Dr. Collins.

[Keely Savoie @ American Thoracic Society]

People with high blood pressure appear to be less likely to have migraine than those with low blood pressure. Researchers say stiff arteries associated with high blood pressure may play a role in protecting against migraine. The research is published in the April 15, 2008, issue of Neurology, the medical journal of the American Academy of Neurology.

Researchers tested the blood pressure of 51,353 men and women over the age 20 in Norway, including the systolic, diastolic and pulse pressure rates. Pulse pressure is the change in blood pressure when the heart contracts. The rate is determined by subtracting the diastolic blood pressure, the bottom number, from the systolic blood pressure, or the top number.

The participants also completed a survey on the presence and frequency of headaches and their use of blood pressure medications.

The study found people with higher systolic blood pressure were up to 40 percent less likely to have a headache or migraine compared to people with healthier blood pressure rates.

“Higher pulse pressure was linked to up to a 50-percent reduction in the amount of headache and migraine for both men and women,” said study author Erling Tronvik, MD, with the Norwegian National Headache Center at Trondheim University Hospital in Trondheim, Norway. “The finding was not as strong, however, for people who were taking blood pressure medications, which are sometimes used to treat migraine.”

Tronvik says both high systolic blood pressure and pulse pressure are related to stiff arteries and that may decrease the risk of headaches by affecting the baroreflex arch. “The baroreflex arch helps maintain blood pressure, but when it is affected, it can cause hypoalgesia, a condition that makes a person less sensitive to pain,” said Tronvik.

Tronvik says these results confirm previous studies which have found that increasing blood pressure is linked to decreasing amounts of chronic pain in all parts of the body.

[Angela Babb @ American Academy of Neurology]

Inserting tiny scaffolding into the brain could dramatically reduce damage caused by strokes the UK National Stem Cell Network Annual Science Meeting will hear today. With funding from the Biotechnology and Biological Sciences Research Council (BBSRC) neurobiologists from the Institute of Psychiatry and tissue engineers from The University of Nottingham have joined forces to tackle the challenge of tissue loss as a result of stroke.

Speaking at the conference in Edinburgh, Dr. Mike Modo from the Institute of Psychiatry will explain how combining scaffold microparticles with neural stem cells (NSCs) could regenerate lost brain tissue.

Strokes cause temporary loss of blood supply to the brain which results in areas of brain tissue dying - causing loss of bodily functions such as speech and movement. Neural Stem Cells offer exciting possibilities for tissue regeneration, but there are currently major limitations in delivering these cells to the brain. And while NSC transplantation has been proven to improve functional outcomes in rats with stroke damage little reduction in lesion volume has been observed.

The research is being carried out by Dr. Mike Modo and Professor Jack Price from the Institute of Psychiatry and Professor Kevin Shakesheff from The University of Nottingham.

Their findings are being presented at the UK National Stem Cell Network Inaugural Science Meeting at the Edinburgh Conference Centre on 10 April 2008. The conference is a showcase of the best and latest UK stem cell science across all stem cell disciplines.

Working with rats, Dr. Modo and his team are developing cell-scaffold combinations that could be injected into the brain to provide a framework inside the cavities caused by stroke so that the cells are held there until they can work their way to connect with surrounding healthy tissue.

Dr. Modo explains: “We propose that using scaffold particles could support NSCs in the cavity to re-form the lost tissue and provide a more complete functional repair. The ultimate aim is to establish if this approach can provide a more efficient and effective repair process in stroke.”

Kevin Shakesheff, Director of The University of Nottingham’s new £25m Centre for Biomolecular Sciences and Professor of Tissue Engineering in the School of Pharmacy, said: “Within the body our cells function within tightly controlled 3D architectures. Our scaffolds can recreate some of the architectural features and thereby protect the cells and help them to integrate and function.”

The team hope their work will pave the way for NSCs to be successfully used in clinical settings to re-develop parts of the brain damaged by stroke and neurodegenerative diseases.

[Dr. Mike Modo @ University of Nottingham]

A medical student places a chest tube in a patient lying on an operating table, while another student conducts a colonoscopy. Everything is just as it would be in a real OR or treatment room, except that the patients won’t be harmed or complain if mistakes are made — they’re robots.

These high-tech, electronically outfitted mannequins are equipment in the new $5 million medical and surgical simulation training center at the Johns Hopkins Outpatient Center in East Baltimore that opened in March.

The ’sim’ center contains two fully operational ORs, two intensive care units (ICUs), high-fidelity computerized mannequins that mimic physiologic and behavioral response to procedures, and 12 examination rooms where students practice routine exams on actors posing as patients with particular complaints and symptoms.

The mannequins have breath sounds and heart tones, palpable pulses, and a monitor that displays vital signs as students, physicians, nurses and other health care professionals practice everything from bag-mask ventilation, intubation, and defibrillation to chest tube placement and endoscopies. Computer programs test decision making skills and knowledge on topics such as advanced cardiac life support and trauma management.

“The idea is to get it right before they treat real patients,” says the center’s director, Elizabeth Hunt, M.D., M.P.H., assistant professor in the Department of Anesthesiology and Critical Care Medicine.

The troupe of paid professional actors who are trained to portray patients submit themselves to trainees who practice taking histories, performing physical exams, breaking bad news and communicating in a compassionate manner.

“Students can learn the science of medicine in many different ways, but there is only one good way to learn good bedside manner, and that is with real people,” says Hunt.

Each of the 15 simulation rooms in the center is equipped with adjustable cameras, microphones, one-way glass for observer viewing, and large flat-screen monitors so students and staff can quickly review their performance while it’s still fresh in their minds.

In addition to training students and staff, Hunt says the center also will be used to train medical staff on new equipment, and for teaching emergency medical technicians and paramedics. Outside groups may also be welcome during continued medical education seminars.

[Eric Vohr @ Johns Hopkins Medical Institutions]

For the first time, the association between Parkinson’s disease and exposure to pesticides has been shown in patients with the neurological disorder compared with their unaffected relatives, according to a study in the online open access journal BMC Neurology.

Parkinson’s disease is a common neurological disorder affecting about 1 million people in the USA. The disorder typically develops in later life resulting in symptoms such as tremors and muscle rigidity

Although variations in several genes have been identified that contribute to the disease, these rare genetic defects account for a small proportion of the overall prevalence of the disorder.

The majority of Parkinson’s disease cases are thought to be due to an interaction between genetic and environmental factors.

“Previous studies have shown that individuals with Parkinson’s disease are over twice as likely to report being exposed to pesticides as unaffected individuals” says the study’s lead author, Dana Hancock, “but few studies have looked at this association in people from the same family or have assessed associations between specific classes of pesticides and Parkinson’s disease.”

The study of related individuals who share environmental and genetic backgrounds that might contribute to Parkinson’s disease enables researchers to identify specific differences in exposures between individuals with and without the disease. The research team from Duke University Medical Center (Durham, NC) and the University of Miami Miller School of Medicine Morris K. Udall Parkinson Disease Research Center of Excellence (Miami, FL, USA) recruited 319 patients and over 200 relatives. They used telephone interviews to obtain histories of pesticide exposure, living or working on a farm, and well-water drinking.

The authors detected an association between pesticide use and Parkinson’s disease. Among these, the strongest were between the disorder and use of herbicides and insecticides, such as organochlorides and organophosphates. No association was found between Parkinson’s disease and well-water drinking or living or working on a farm, which are two commonly used proxies for pesticide exposures.

Many studies have supported pesticides as a risk factor for PD, but “biological evidence is presently insufficient to conclude that pesticide exposure causes PD”, says Hancock. “Further investigation of these specific pesticides and others may lead to identification of pertinent biological pathways influencing PD development.” In addition future genetic studies of Parkinson’s disease should consider the influence of pesticides, since exposure to pesticides may provide a trigger for the disease in genetically predisposed individuals.

[Charlotte Webber @ BioMed Central]

After nearly ten years of research and development, scientists at SUNY Downstate Medical Center in Brooklyn and Peking University in Beijing were awarded a United States patent for their virtual telemicroscope. This patented software permits off-site pathologists to diagnose cancer or other diseases in patients living in remote locations around the world.

Virginia M. Anderson, MD, associate professor of pathology at SUNY Downstate, and Jiang Gu, MD, PhD, dean and chairman of pathology at Peking University, developed the virtual microscope system, the only one of its kind capable of emailing electronic slides. Using their patent, the Chinese company Motic — a global leader in microscope manufacturing — created a microscope with a robotic stage that scans whole slides at various magnifications and then creates compressed images that can be emailed all over the world.

In China, where the device is being tested as a diagnosis instrument, 600 hospitals do not have an on-site pathologist. The system was developed with that fact in mind.

“Enormous voids in pathology services exist. Virtual slides are definitely going to improve diagnostic accuracy and healthcare,” says Dr. Anderson.

The Motic telepathology system utilizes a computer and microscope, which enables interactive communication on a user network. A robot scans the whole tissue sample on the microscope. Subsequent images corresponding to the selected area of the specimen are linked at higher magnifications. The patented software turns an ordinary computer into a virtual microscope. High magnification images are compressed and linked to the low power scanned glass slide that is stored as a virtual slide file. Images can then be emailed and analyzed by pathologists at remote locations. Once received, Internet independent images can be stored and viewed as part of the electronic medical record or medical student teaching file.

“The virtual telemicroscope is designed the way pathologists think and work,” Dr. Anderson says, adding, “A pathologist would never scan an entire histopathologic section at high power. This is inefficient and unnecessary. Slides prepared by an experienced pathologist will focus on important areas to make a diagnosis.”

Clinical trials showed that Motic’s virtual telemicroscope is “as good as or better than the competition.” The system is also teaching-friendly, allowing professors to manipulate existing digital slides and create new slides for students to study.

The next generations of medical students and pathologists are being taught through interactive technology. The virtual telemicroscope will save time and money, improve medical education, and provide insight into the pathogenesis of disease. Microscopes will be used to prepare whole slide images for analysis on a big screen or laptop computer.

The SUNY Downstate system produces the only virtual slides that can be emailed around the world. Moreover, it is also the least expensive, Internet independent solution for expert consultation. Clinical trials published in the journal, Human Pathology (February 2008), confirm the diagnostic accuracy of virtual slides as compared to traditional methods.

[Ron Najman @ SUNY Downstate Medical Center]

The risks of increasing people’s access to over-the-counter medicines may outweigh the benefits, warn experts in this week’s BMJ.

They suggest that the safety of over-the-counter medicines should be kept under close review and that patients should be urged to report any adverse reactions.

Medicines are currently divided into classes that do or do not require prescription, write Robin Ferner, Director at the West Midlands Centre for Adverse Drug Reactions and Keith Beard, Consultant Physician at the Victoria Infirmary Glasgow.

Prescription only medicines are subject to a range of controls that are relaxed when medicines are made more freely available over the counter.

When deciding if a medicine should be reclassified to make it available over the counter, regulatory authorities must balance the benefits of easier access against the potential harm from unsupervised or inappropriate use.

Once medicines have been reclassified, they remain subject to safety review.

Patients, doctors and pharmacists can all benefit if medicines are available over the counter. For example, patients can call at a pharmacy any time rather than waiting to see a doctor, general practitioners no longer need to write prescriptions for minor ailments, and pharmacists can make better use of their professional skills.

Drug companies and retail pharmacies can also expect to benefit commercially from reclassification of medicines as over the counter.

However, there are worries about over-the-counter medicines, say the authors. For instance, a patient who makes the wrong diagnosis and uses an inappropriate over-the-counter medicine may present late with a potentially serous but treatable condition. Prescribers also have no opportunity to reinforce instructions for safe use as they can with prescribed medicines.

Regulators can reduce the potential for harm of over-the-counter medicines by specifying the concentration, dose, or pack size that a pharmacist can supply without prescription. However some drugs, such as statins, are probably less effective in low doses than in the higher doses usually prescribed.

Internet shopping now also makes it straightforward, if risky, to order medicines without involving a doctor or pharmacist in the decision. The Royal Pharmaceutical Society of Great Britain estimates that two million Britons obtain their medicines that way.

So what needs to be done to increase the safety of over-the-counter medicines, ask the authors”

The safety of over-the-counter medicines has to be continually reviewed, even though this is difficult in practice, they say. Since healthcare professionals may not be involved, we have to rely on patients to report adverse effects. A new website allowing patients to report adverse drug reactions to the UK Yellow Card scheme could be helpful.

Regulators should also ask for clearer evidence of benefit at the over-the-counter dose if this is lower than the dose usually prescribed, they conclude.

[Rachael Davies @ BMJ-British Medical Journal]

HCV is a significant human pathogen, infecting more than three percent of the world’s population. The incidence of infection in the United States has been estimated to be as high as 4 million cases. In the March issue of the journal PLoS Pathogens, Timothy Tellinghuisen, an assistant professor in the Department of Infectology at Scripps Florida, and his colleagues describe how they used mutations of the viral NS5A phosphoprotein to disrupt virus particle production at an early stage of assembly. NS5A has long been proposed as a regulator of events in the HCV life cycle, but exactly how it orchestrates these events has been unclear.

“The interesting thing about this mutant is that while it triggers totally normal RNA replication, it causes severe defects in the output of infectious virus-in fact, it releases no infectious virus that we can detect,” says Tellinghuisen. “And though this discovery isn’t a cure for HCV, it is an important research tool that stops the assembly pathway.” Total disruption of the replication process would be a cure for the disease, he adds, and that’s the team’s long-term goal.

HCV infection is roughly five to seven times more prevalent than HIV, underscoring the pandemic nature of HCV infection. HCV occurs when blood from an infected person enters the body of someone who is not infected. Most new HCV infections are due to illegal drug injections and sharing needles. However, those who had blood transfusions prior to blood donor screening in 1991, healthcare workers who had needle stick accidents, and hemodialysis patients are also at risk for developing HCV infection. The virus predominantly infects the liver, and following many decades of virus reproduction serious disease such as hepatitis (liver inflammation), cirrhosis (liver scarring), and carcinoma (liver cancer) develop. Ultimately, HCV infection destroys the liver, resulting in death. Attempts at curing HCV infections with drug therapy have been only marginally successful.

Before more effective therapies can be developed, scientists need to understand, at the molecular level, the detailed mechanisms HCV uses to infect cells, replicate itself, assemble progeny virus, and exit the cell. Each of these processes could potentially be a target for a new drug to eliminate HCV infection. HCV, like all viruses, requires the normal cellular machinery for its replication and has developed strategies to utilize normal cell physiology for its own benefit (often to the detriment of the host).

The Tellinghuisen team, which includes Research Assistants Katie L. Foss and Jason Treadaway, has focused recent efforts on NS5A to understand the regulation of events used by the virus to assemble infectious copies of itself and exit the cell. NS5A is a three-domain protein, which means it is comprised of three compactly folded regions roughly 50 to 300 amino acids in length. The requirement of domains I and II for RNA replication is well documented. NS5A domain III, however, is not required for RNA replication, and the function of this region in the HCV life cycle is unknown.

Using standard molecular biology, the researchers removed from domain III of NS5A a coding sequence corresponding to roughly 15 amino acids. Then they generated a clone of the virus, transcribed the RNA from that clone, and purified the RNA. This RNA, which is directly infectious, was then transfected into a liver cell line where it produced all the HCV proteins that are encoded by that RNA genome.

“Those proteins assemble in the cell to make a structure called a replicase that then copies the viral RNA,” Tellinghuisen explains. “We measured that RNA accumulation and observed no defect in RNA replication, but found, surprisingly, that no infectious viral particles were released from the cells.” The team also found that no viral RNA nor nucleocapsid protein are released from cells, indicating that an early event in virus assembly had been affected.

Using genetic mapping and biochemical analyses, the authors were able to show that their deletion altered a phosphorylation signal controlling the switch from RNA replication to virus particle assembly. This signal was attributed to the activity of a cellular kinase that when inhibited by genetic or chemical means led to a reduction in infectious virus production without altering HCV RNA replication.

“These data provide the first evidence for a function of domain III of NS5A and implicate NS5A as an important regulator of the RNA replication and virion assembly of HCV,” Tellinghuisen says. “The ability to uncouple virus production from RNA replication may be useful in understanding HCV assembly and may become therapeutically important.”

Charles M. Rice, head of the Center for the Study of Hepatitis C at Rockefeller University, comments, “This is a spectacular advance linking a specific phosphorylation event by a cellular kinase to hepatitis C virus assembly. Remarkably, the target is a viral nonstructural protein, NS5A, and the data point to a pivotal role for this protein in regulating RNA amplification and infectious virus production. These new data make this multifunctional protein an even more attractive target for developing new anti-virals for treating hepatitis C.”

[Keith McKeown @ Scripps Research Institute]

Gnomie Robert Frederick writes:

Hello, Chris! I thoroughly enjoyed your chat with Earl Thibert; it is nice to know that his disability hasn’t prevented him from being who he wants to be. I applaud him heavily for what he’s doing, though I would love to ask him how he got into computers. I feel bad because I am not as open about having cerebral palsy as he is, but since mine isn’t severe, I just prefer to stand aside and let those who have it worse than I do take center stage. The odd thing is that I was reading this article at CNN.com when you started your chat with Earl.

It’s kind of a sad article, but an example of what can happen when CP is as bad as it gets (not that the parents helped matters, either). The doctors said that I would also be totally dependent on my mother — pretty much a vegetable. Fortunately it didn’t turn out that way, and I had some good teachers that helped me along the way. It was one of these teachers who had a little extra class that involved activities with Apple IIes. I had a lot of fun with these machines. There were five set up along a wall in the library, three of which had ImageWriter printers. I always tried to get one that the printer hooked up to, as I thoroughly enjoyed making it print banners and other things, just to watch the thing work. Lots of fun times.

I have been trying to get an Apple IIe since, though I actually have an ImagreWriter printer now. As computers go, it was utter simplicity in its operation. You turned the thing on and put the appropriate disk in the floppy drive, typed in a command, and away it went. No activation key, no UAC, no blue screens. Just a simple task of waiting for the program to load. Those were the days.

Oddly enough, the desire to build systems didn’t strike me until I met another librarian in about 1991. He had (at the time) a top-of-the-line, IBM 486-based system with Prodigy Internet, an external 14.4 modem, and a Pioneer 12-disk CD-ROM changer. (I have not seen anything like it since.) It outclassed my mother’s Tandy 1000 TL/2 by a country mile (she’s ashamed to admit that she had that system, by the way. Please do not mention it to her). This librarian was an older guy, but knew quite a bit about the system he had. I credit him with pushing me to get more interested in computers.

At this point I was getting pretty good at being able to completely dismantle a handheld game and reassemble it again. Oddly enough, the most logical thing to do in order to learn to build a system was to take one apart. And guess which system I took apart? The Tandy. It also subsequently became the first system I would clean. Successfully putting it back together again was slow, but it resulted in a machine that was much cleaner than it was before. Mother never knew I had done it, either, and the machine worked perfectly for seven more years (before a dead keyboard BIOS finished it off)! It was fun, but it was only one machine and I was starting to want more.

It took a while, but in 1995 I got a pile of 8088 parts and a dead 8088 system to tinker with from my Uncle Joe, who at this point had picked up on the same thing that the librarian had picked up on four years earlier. One day I spread all of the parts out in front of me, and started working. That was pretty much the way it started. I fixed that dead 8088, and built another. Things went faster after that. 8088 parts became 286, 386, and then 486 parts within a year and a half. The same with the operating systems I used. Direct Access 5.1 became Windows 3.11, and Windows 95 just as fast.

My brother-in-law came into the picture about ‘96-’97, and from his job came my first DX2 66 processor with more RAM, 98 SE, and later, the first real influx of Pentium class parts. At the time I had replaced my 386 DX 40 system (bought at a yard sale for $20 — my first self-bought system) with a 486 DX 2 66 system with 16 MB of RAM and my first 200+ MB drive running Windows 98 SE. this was the system I first got on the Internet with — using a Sportster 14.4 modem!

It wasn’t long after I started using the Internet regularly that my brother-in-law cued me into an e-mail newsletter that he was a big fan of (can you guess who it was by? He hailed from Des Moines, Iowa). It was my first newsletter subscription. I remember him making that Lockergnome Winamp skin that is now lost to time. For the life of us both, we could never find it — or any copy of it for that matter. I got my first taste of Windows 2000 in 2000, of course! After mother helped me build an AMD 400 MHz system with 64 MB of PC 100 RAM and a whopping 6 GB hard drive. I housed the whole mess in an 11-bay, $35 beige tower that had included a 350w PS.

It’s pretty much a blur after that. Windows 2000 gave way to a much anticipated OS called Windows XP, and the systems I worked on flew by as well Dells, HPs, Compaqs, DECs, eMachines, generics (41 systems [mostly gutted] that someone gave me from an auction), and eventually Macs. They were in all types of conditions from near-mint to an HP that I got a couple of months ago that was probably the worst system that I have ever had to clean. I actually had to take this machine outside to work on it. Roaches are the bane of our existence down here in the Florida Panhandle — not the big kind, but the kind that are apparently small enough to turn a neglected 2 GHz Celeron HP into a massive colony. The person had taken one of my Dell 500 MHz systems in exchange for this thing, which she said was no longer reading CDs. Understatement of the year! If I had known what I was going to be dealing with I would have simply tossed it. I guess if your CD-ROM drive were full of roaches and bugs, it wouldn’t read discs either.

“Brown powder” is apt to describe what came out of this system. I tossed the case, power supply, CD-ROM drive, and floppy drive, and scrubbed the board down with isopropyl alchohol. The original 20 MB hard drive was also salvageable, as it actually was one of the cleanest parts of the machine. I was able to mount the thing in a generic case and basically provide my brother with a 2 GHz Celeron system with 512 MB of RAM and a 20 GB hard drive. All for only the cost of the case and power supply. Not bad, but I wouldn’t do it again!

Anyway I’m sorry for the long email (again), but I figured I would let you know a little more about how I have come to view computers as a lifestyle and as a hobby. My disability has prevented me from doing a lot of sports and sometimes I do wish I could do more than I do, but computers are my outlet, and I pretty much go crazy unless I’m working on one (even when I stay up until 5 in the morning, much to my mother’s dismay). So I shouldn’t complain. Some people say it’s a gift having learned what I have without setting foot in a computer literacy classroom, but I just take it in stride. I build and fix systems, just to do it, be it as a favor, or just to donate the system once I’m through cleaning it. After all, I’d rather someone get a chance to have a system rather than see it go into the trash. It’s been a long road from my first experiences with that Apple IIe all those years ago, but I hope that I have a ways to go yet.

A new study appears to explain how humans, along with other higher primates, guinea pigs and fruit bats, get by with what some have called an “inborn metabolic error”: an inability to produce vitamin C from glucose.

Unlike the more than 4,000 other species of mammals who manufacture vitamin C, and lots of it, the red blood cells of the handful of vitamin C-defective species are specially equipped to suck up the vitamin’s oxidized form, so-called L-dehydroascorbic acid (DHA), the researchers report in the March21st issue of Cell, a publication of Cell Press. Once inside the blood cells, that DHA — which is immediately transformed back into ascorbic acid (a.k.a. vitamin C) — can be efficiently carried through the bloodstream to the rest of the body, the researchers suggest.

“Evolution is amazing. Even though people talk about this as an ‘inborn error’-a metabolic defect that all humans have-there is also this incredible manner in which we’ve responded to the defect, using some of the body’s most plentiful cells,” said Naomi Taylor of Université Montpellier I and II in France, noting that the body harbors billions of red blood cells. “[Through evolution], we’ve created this system that takes out the oxidized form of vitamin C and transports the essential, antioxidant form.”

Meanwhile, the red cells of other mammals apparently take up very little, if any, DHA, which might explain why they need to produce so much more vitamin C than we need to get from our diets, Taylor said. The recommended daily dose of vitamin C for humans is just one mg/kg, while goats, for example, produce the vitamin at a striking rate of 200 mg/kg each day.

In essence, the red cells of animals that can’t make vitamin C recycle what little they’ve got. Earlier studies had described the recycling process, Taylor said. “Our contribution to the whole story is to show that this process of recycling exists specifically in mammals that don’t make vitamin C.”

Scientists knew that the protein called Glut1, found in the membranes of cells throughout the body, is the primary transporter of glucose. They also knew that Glut1 can transport DHA too, thanks to the structural similarities between the two molecules. In biochemical assays, it appeared that the glucose transporter would move glucose and DHA interchangeably.

But, in the new study, Taylor’s group made a surprising discovery: The Glut1 on human red blood cells strongly favors DHA over glucose. In fact, the human blood cells are known to carry more Glut1 than any other cell type, harboring more than 200,000 molecules on the surface of every cell. Nevertheless, the researchers found, as red blood cells develop in the bone marrow, their transport of glucose declines even as Glut1 numbers skyrocket.

The key to the glucose transporters switch to DHA, they show, is the presence of another membrane protein called stomatin. (Accordingly, in patients with a rare genetic disorder of red cell membrane permeability wherein stomatin is only present at low levels, DHA transport is decreased by 50% while glucose uptake is significantly increased, they report.)

Then, another surprise: The researchers found that the red cells of mice, a species that can produce vitamin C, don’t carry Glut1 on their red blood cells at all. They carry Glut4 instead. They suspected that the differences in human red blood cells might be linked to our inability to synthesize the reduced form of DHA, vitamin C, from glucose. In fact, they confirmed Glut1 expression on human, guinea pig and fruit bat red blood cells, but not on any other mammalian red cells tested, including rabbit, rat, cat, dog and chinchilla. Next, they took a closer look at primates. Primates belonging to the Haplorrhini suborder (including prosimian tarsiers, new world monkeys, old world monkeys, humans and apes) have lost the ability to synthesize vitamin C, whereas primates in the Strepsirrhini suborder (including lemurs) are reportedly able to produce this vitamin, Taylor explained.

Notably, they detected Glut1 on all tested red blood cells of primates within the higher primate group, including long-tailed macaques, rhesus monkeys, baboons and magot monkeys. In marked contrast, Glut1 was not detected on lemur red blood cells. Moreover, they report, although DHA uptake in human and magot red cells was similar, the level of transport in cells from three different lemur species was less than 10% of that detected in higher primates.

“Red blood cell-specific Glut1 expression and DHA transport are specific traits of the few vitamin C-deficient mammalian species, encompassing only higher primates, guinea pigs and fruit bats,” the researchers concluded. “Indeed, the red cells of adult mice do not harbor Glut1 and do not transport DHA. Rather, Glut4 is expressed on their cells. Thus, the concomitant induction of Glut1 and stomatin during red blood cell differentiation constitutes a compensatory mechanism in mammals that are unable to synthesize the essential ascorbic acid metabolite,” otherwise known as vitamin C.

[Cathleen Genova @ Cell Press]

By injecting a customized “genetic patch” into early stage fish embryos, researchers at Washington University School of Medicine in St. Louis were able to correct a genetic mutation so the embryos developed normally.

The research could lead to the prevention of up to one-fifth of birth defects in humans caused by genetic mutations, according to the authors.

Erik C. Madsen, first author and an M.D./Ph.D. student in the Medical Scientist Training Program at Washington University School of Medicine, made the groundbreaking discovery using a zebrafish model of Menkes disease, a rare, inherited disorder of copper metabolism caused by a mutation in the human version of the ATP7A gene. Zebrafish are vertebrates that develop similarly to humans, and their transparency allows researchers to observe embryonic development.

Children who have Menkes disease have seizures, extensive neurodegeneration in the gray matter of the brain, abnormal bone development and kinky, colorless hair. Most children with Menkes die before age 10, and treatment with copper is largely ineffective.

The research is published this month in the Proceedings of the National Academy of Sciences’ advance online edition.

The development of organs in the fetus is nearly complete at a very early stage. By that time, the mutation causing Menkes disease has already affected brain and nerve development.

Madsen and Bryce Mendelsohn, also an M.D./Ph.D. student at the School of Medicine, wondered if they could prevent the Menkes-like disease in zebrafish by correcting genetic mutations that impair copper metabolism during the brief period in which organs develop. Both students work in the lab of Jonathan D. Gitlin, M.D., the Helene B. Roberson Professor of Pediatrics at the School of Medicine and director of Genetics and Genomic Medicine at St. Louis Children’s Hospital.

The researchers used zebrafish with two different mutations in the ATP7A gene, resulting in a disease in the fish that has many of the same characteristics of the human Menkes disease. Madsen designed a specific therapy to correct each mutation with morpholinos, synthetic molecules that modify gene expression. The zebrafish embryos were injected with the customized therapy during the critical window of development, and the researchers found that the zebrafish hatched and grew without any discernable defects.

“This method of copper delivery suggests that the prevention of the neurodegenerative features in Menkes disease in children may be possible with therapeutic interventions that correct the genetic defect within a specific developmental window,” Madsen said.

The genetic mutations Madsen and the researchers worked with are caused by splicing defects, or an interruption in genetic code. The morpholinos prevent that interruption by patching over the defect so the gene can generate its normal product.

“Consider the genetic code as a book, and someone has put in random letters or gibberish in the middle of the book,” Madsen said. “To be able to read the book, you have to ignore the gibberish. If we can make cells ignore the gibberish, or the splicing defect, the fetus can develop normally.”

Up to 20 percent of genetic diseases are caused by splicing defects, Madsen said, so this treatment method could potentially be used for many other genetic diseases.

“The idea is that we can modify the treatment to target a specific mutation and design molecules to alter gene function in the same way the morpholino oligonucleotides can,” Gitlin said.

The work is an important step toward personalized medicine, which can tailor treatment to an individual’s genetic makeup.

“Eventually we would like to know each person’s genome sequence so we know what mutations each person has that may lead to disease,” Gitlin said. “That way, you don’t get a drug for cancer that works against any kind of cancer, you get a drug for the specific mutation that causes your cancer. That’s what personalized medicine is all about.”

Beth Miller @ Washington University in St. Louis]

Botulinum toxin, also called Botox, is best known as one of the most commonly used molecules to reduce wrinkles. It is also known as one of the most poisonous naturally occurring substances.

Now, thanks to Dr. Sam Daniel, Associate Director of Research of the Otorhinolaryngology Division at the Montreal Children’s Hospital of the McGill University Health Centre, this protein has become an effective method to save newborns suffering from CHARGE Syndrome from having to undergo devastating tracheotomies. Dr. Daniel describes the case of the first infant patient treated with the toxin in an article from the Archives of Otolaryngology dated March 17th.

CHARGE Syndrome is rare, but it can become life-threatening in its most severe form. The syndrome includes a variety of birth defects in different organs, such as the heart, eyes or ears, but it also affects the salivary glands. They are hyper-stimulated and secrete excessive fluids that are discarded into the lungs, causing asphyxia. This was the case for the patient that Dr. Daniel discusses in his article: at the age of two and a half months, little Franck (not his real name) was still unable to breathe without assistance and a tracheotomy seemed inevitable in order to relieve his respiratory system.

Seeing the despair of Franck’s parents, Dr. Daniel proposed an experimental treatment as a last recourse: the injection of a minute dose of Botox into each of Franck’s salivary glands. This had never been done before on such a young child, but no other option could prevent permanent intubation. Two weeks after the injections, Franck’s extubation was a success. He now leads the normal life of a three-year-old boy at home with his parents.

Botulinum toxin is a very powerful neurotoxin, meaning that it blocks nerve activity. In Franck’s case, it blocked the nerves that stimulated his salivary glands thereby reducing their secretions to a normal level. The infant then needed repeated injections every four to six months for one and a half years until his glands shrunk and stopped overproducing saliva.

Since this first attempt five years ago, Dr. Daniel has performed over 1000 Botox injections in young children including 12 in newborns. “This treatment is extremely effective, and to date I have not encountered any major side effects despite the bad press Botox got recently. It also helps us considerably improve the lives of our patients,” he explained.

[Isabelle Kling @ McGill University Health Centre]

Two major eye diseases and leading causes of blindness — age-related macular degeneration and diabetic retinopathy — can be reversed or even prevented by drugs that activate a protein found in blood vessel cells, researchers at the University of Utah School of Medicine and several other institutions have announced in a new study.

Damage from both diseases was prevented and even reversed when the protein, Robo4, was activated in mice models that simulate age-related macular degeneration (AMD) and diabetic retinopathy, according to Dean Y. Li, M.D., Ph.D., senior author of the study published March 16 in Nature Medicine online.

Robo4 treated and prevented the diseases by inhibiting abnormal blood vessel growth and by stabilizing blood vessels to prevent leakage. Abnormal blood vessel growth and leakage are two primary factors in both age-related macular degeneration (AMD) and diabetic retinopathy. But the study’s ramifications go beyond eye diseases.

Serious infections such as SARS (Severe Acute Respiratory Syndrome), for example, kill people when an infection destabilizes blood vessels, allowing fluids to leak into the lungs. Tumors hijack blood vessel growth to feed on nutrients and grow. Although this study did not prove Robo4 would treat those diseases, Li believes it merits investigation.

“Many diseases are caused by injury or inflammation destabilizing blood vessels and causing them to leak fluid into adjacent tissues as well,” said Li, professor of internal medicine and an investigator with the University’s Program in Human Molecular Biology and Genetics. “We found a natural pathway - the Robo4 pathway - that counterattacks this by stabilizing blood vessels.”

“This discovery has significant implications for developing drugs that activate Robo4 to treat AMD and diabetic retinopathy,” said Kang Zhang, M.D., Ph.D., associate professor of ophthalmology and visual sciences at the University of Utah’s John A. Moran Eye Center and an investigator with the University’s Program in Human Molecular Biology and Genetics. Li and Zhang’s laboratories closely collaborated on the research, using the same animal models of AMD and diabetic retinopathy that are required for drug development. The collaboration means the time required to test the approach in people could be shortened, perhaps by years. Nonetheless, both Zhang and Li caution that getting new drugs to market still would take a number of years.

Randall J. Olson, M.D., director of the University’s John A. Moran Eye Center and professor and chair of ophthalmology and visual sciences, called Li’s finding historic.

“This is a major breakthrough in an area where the advances have been minimal,” Olson said. “We are excited about taking this opening and moving the frontier forward with real hope for patients who have but few, often disappointing, options.”

The discovery is a prime example of basic science research yielding a discovery with direct clinical applications, according to Hemin Chin, Ph.D., director of ocular genetics program at the National Eye Institute. “Given that vascular eye diseases, such as age related macular degeneration and diabetic retinopathy, are the number one cause of vision loss in the United States, the identification of new signaling pathways that prevent abnormal vessel growth and leakage in the eye represents a major scientific advancement,” said Chin.

Blood vessel growth (angiogenesis) is critical in human development and as a response to injury or disease. In earlier research, Li had shown that a family of proteins, netrins, induce blood vessel and nerve growth in mice, a discovery with important ramifications for potential therapies to help people with too few blood vessels. But when the body grows new blood vessels at the wrong time or place, these blood vessels are often unstable and weak, which causes them to leak and potentially lead to diseases such as macular degeneration and diabetic retinopathy.

In 2003, Li’s laboratory cloned Robo4 and showed it served the opposite function of netrins by inhibiting blood vessel growth and the destabilization that causes leakage. Robo4 is found only in cells in the interior surface of blood vessels and is activated by a protein called Slit. After being activated, Robo4 initiates a chain of biochemical events to stabilize blood vessels and prevent uncontrolled growth.

“Everything in biology has a yin (negative) and a yang (positive), and in the previous paper on netrins we brought attention to a new signaling pathway that induces vessels and nerves to grow,” Li said. “Robo4 is the yin to that process, preventing new vessel growth by stabilizing the integrity of mature blood vessels.”

Age-related macular degeneration is the most common cause of legal blindness in people age 65 or older and is expected to become an increasingly common and costly health issue as the number of older people in United States increases. Diabetic retinopathy is the most common cause of legal blindness in working-age Americans. Currently, there are an estimated 21 million people with diabetes.

[Chris Nelson @ University of Utah Health Sciences]

A new study shows that exposure to a chemical called diacetyl, a component of artificial butter flavoring, can be harmful to the nose and airways of mice. Scientists at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, conducted the study because diacetyl has been implicated in causing obliterative bronchiolitis (OB) in humans. OB is a debilitating but rare lung disease, which has been detected recently in workers who inhale significant concentrations of the flavoring in microwave popcorn packaging plants.

When laboratory mice inhaled diacetyl vapors for three months, they developed lymphocytic bronchiolitis - a potential precursor of OB. None of the mice, however, were diagnosed with OB.

“This is one of the first studies to evaluate the respiratory toxicity of diacetyl at levels relevant to human health. Mice were exposed to diacetyl at concentrations and durations comparable to what may be inhaled at some microwave popcorn packaging plants,” said Daniel L. Morgan, Ph.D., head of the Respiratory Toxicology Group at the NIEHS and co-author on the paper that appears online in the journal, Toxicological Sciences. The study was done in collaboration with Duke University researchers.

The authors conclude that these findings suggest that workplace exposure to diacetyl contributes to the development of OB in humans, but more research is needed.

Although exposure of laboratory animals by inhalation closely duplicates the way humans are exposed to airborne toxicants, the study points out that some anatomical differences between the mice and humans may account for why the nasal cavity of mice is more susceptible to reactive vapors than that of humans. Another reason may be that mice breathe exclusively through their noses.

The researchers also speculate that the extensive reaction of diacetyl vapors in the nose and upper airways of mice may have prevented toxic concentrations from penetrating deeper in the lung to the bronchioles or tiny airways where obstruction occurs in humans.

When the mice were exposed to high concentrations of diacetyl using a method that bypasses the nose, the researchers found lesions partially obstructing the small airways. More studies are under way to determine if these lesions progress to OB in mice.

The National Toxicology Program, headquartered at the NIEHS, plans to do a larger set of studies to provide inhalation toxicity data on artificial butter flavoring and the two major components, diacetyl and another compound called acetoin. The NTP studies will help pinpoint more definitively the toxic components of artificial butter flavoring and potentially help identify biomarkers for early detection. The NTP data will then be shared with public health and regulatory agencies so they can set safe exposure levels for these compounds and develop guidance to protect the health of workers in occupations where these chemicals are used.

[Robin Mackar @ NIH/National Institute of Environmental Health Sciences]

When human umbilical cord blood cells (UCBC) were injected into aged laboratory animals, researchers at the University of South Florida (USF) found improvements in the microenvironment of the hippocampus region of the animals’ brains and a subsequent rejuvenation of neural stem/progenitor cells.

Published online at BMC Neuroscience, the research presented the possibility of a cell therapy aimed at rejuvenating the aged brain.

“Brain cell neurogenesis decreases dramatically with increasing age, mostly because of a growing impoverishment in the brain’s microenvironment,” said co-author Alison Willing, PhD, of the USF Center of Excellence for Aging and Brain Repair. “The increase in neurogenesis we saw after injecting UCBCs seemed to be due to a decrease in inflammation.”

According to lead author Carmelina Gemma, Ph.D., of the James A. Haley Veterans Administration Medical Center (VA) and USF, the decrease in neurogenesis that accompanies aging is a result of the decrease in proliferation of stem cells, not the loss of cells.

“In the brain, there are two stem cell pools, one of which resides in the hippocampus,” explained graduate student and first author Adam Bachstetter. “As in other stem cell pools, the stem cells in the brain lose their capacity to generate new cells. A potent stressor of stem cell proliferation is inflammation.”

Prior to this study, the research team led by Paula C. Bickford, Ph.D., of the VA and USF found that reducing neuroinflammation in aged rats by blocking the synthesis of the pro-inflammatory cytokine IL1? rescued some of the age-related decrease in neurogenesis and improved cognitive function.

“We think that UCBCs may have a similar potential to reduce inflammation and to restore some of the lost capacity of stem/progenitor cells to proliferate and differentiate into neurons,” said Dr. Bickford.

The study found that the number of proliferative cells increased within 24 hours following the UCBC injections into the aged laboratory rats and that the increased cell proliferation continued for at least 15 days following a single treatment.

“We have shown that injections of UCBCs can reduce neuroinflammation,” concluded co-author Paul R. Sanberg, Ph.D. D.Sc. director of the Center of Excellence for Aging and Brain Repair. “Our results raise the possibility that a cell therapy could be an effective approach to improving the microenvironment of the aged brain and restoring some lost capacity.”

The USF study was supported by the National Institutes of Health and the VA Medical Research Service.

Citation: Bachstetter, AD, Pabon, MM, Cole, MJ, Hudson, CE, Sanberg, PR, Willing, AE, Bickford, PC, Gemma, C. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain. BMC Neuroscience, 9(1), 2008, 22 (Epub ahead of print).

[Randy Fillmore of USF Health]

Previous studies have pointed out the benefits of moderate alcohol consumption as a factor in lowering cardiovascular risk. In a study conducted by the Department of Family Medicine at the Medical University of South Carolina and published in the March 2008 issue of The American Journal of Medicine, researchers found that middle-aged non-drinkers who began consuming moderate amounts of alcohol saw an immediate benefit of lower cardiac disease morbidity with no change in mortality after four years.

Studying 7,697 people between 45 and 64 who were non-drinkers and who were participating in the Atherosclerosis Risk in Communities (ARIC) study over a 10 year period, the authors found that 6% began moderate alcohol consumption (1 drink per day or fewer for women and 2 drinks per day or fewer for men) during the follow-up period. After 4 years of follow-up, new moderate drinkers had a 38% lower chance of developing cardiovascular disease than did their non-drinking counterparts. Even after adjusting for physical activity, Body Mass Index, demographic and cardiac risk factors, this difference persisted.

The study also identified a subset of new drinkers who consumed only wine. When comparing non-drinkers to wine-only drinkers, drinkers of other types of alcohol, and heavy drinkers, the wine-only drinkers had the most significant reduction in cardiovascular events. Drinkers of other types of alcohol also had an advantage over non-drinkers, but the difference did not reach statistical significance.

Writing in the article, Dana E. King, MD, MS, states, “A substantial cardiovascular benefit from adopting moderate alcohol drinking in middle age appears supported by the current study. Any such benefit must be weighed with caution against the known ill consequences of alcohol consumption. While caution is clearly warranted, the current study demonstrated that new moderate drinking lowers the risk of cardiovascular disease without an increase in mortality in a four-year follow up period. The findings suggest that, for carefully selected individuals, a ‘heart healthy diet’ may include limited alcohol consumption even among individuals who have not included alcohol previously.”

[Elsevier Health Sciences]

A University of California, San Diego-led research team has demonstrated that immunization with a stabilized version of a protein found on Streptococcus bacteria can provide protection against Strep infections, which afflict more than 600 million people each year and kill 400,000.

In the March 7 issue of the journal Science, the researchers describe, for the first time, the detailed structure of the streptococcal M protein, which is critical to the virulence of Group A Streptococcus (GAS). GAS causes a wide variety of human diseases including strep throat, rheumatic fever, and the life-threatening “flesh-eating” syndrome called necrotizing fasciitis. Studies were performed using M1 protein, which represents the version of M protein present on the most common disease-associated GAS strains.

The team also produced a variant of M1 protein that stimulates the immune system in mice, without the serious side effects caused by natural M1 protein. They say that their results should help scientists develop M1 protein-based vaccines against GAS.

“Using X-ray crystallography, we determined that M1 protein has an irregular, unstable structure,” explained Partho Ghosh, a professor of chemistry and biochemistry in UCSD’s Division of Physical Sciences. “We created a modified version of M1 with a more stable structure, and found that it is just as effective at eliciting an immune reaction, but safer than the original version of M1, which has serious drawbacks to its use in a vaccine.”

“Certain antibodies that are produced by the immune system against M1 protein have been shown to cross-react with normal human tissues including heart muscle, potentially triggering the serious autoimmune disease known as rheumatic fever,” added Victor Nizet, professor of pediatrics and pharmacy at the UCSD School of Medicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences. “M1 protein can also act as a toxin, producing clotting abnormalities and lung injury when injected into mice. Therefore our results with modified M1 provide very novel insight about the role of M proteins in invasive GAS disease and rheumatic heart disease.”

Because M protein is vital for the survival of GAS in the host, various research groups have been trying to determine its structure for decades. According to Ghosh, M1 is “long and skinny,” which makes it a particularly difficult protein to crystallize. Case McNamara, who solved the protein structure while he was a graduate student working with Ghosh and is the first author on the paper, spent three years optimizing the conditions to crystallize the protein and collect the required data.

In the Science article, the team reported that M1 proteins extend from the surface of Strep bacteria in sets of two that coil around on each other. However, the coils do not meet along the entire length of the protein because imperfections in the protein force the two strands to splay apart. By making small changes to the amino acid building blocks that constitute M1 protein, the researchers were able to develop a version of the protein molecules that coiled together along their entire length.

“This is a crude analogy, but if you imagine that M1 protein is a zipper, then the front half of the molecule is zipped up,” said McNamara, who is currently a postdoctoral fellow at the Genomics Institute of the Novartis Research Foundation. “However, unfavorable amino acids prevent the molecule from zipping up all the way. It was clear from the literature that mutations of these unfavorable amino acids to favorable amino acids would allow the molecule to continue to zip up.”

Unstable coils provide a protein with the flexibility to perform different functions, according to Ghosh. Proteins with structures similar to the original version of M1 are found in the human body, including in heart muscle. The researchers hoped that modifying the structure of M1 would make it less likely that an M1 vaccine would trigger an autoimmune response against heart muscle.

This indeed turned out to be the case. In tests with antibodies against heart muscle, Madeleine Cunningham, a professor of microbiology and immunology at the University of Oklahoma Health Sciences Center, determined that engineered M1 was much less reactive than natural M1. In addition, Annelies Zinkernagel, a postgraduate researcher in Victor Nizet’s laboratory, discovered that unlike mice injected with natural M1, mice injected with stabilized M1 did not develop lung injuries.

Therefore, the instabilities in M1 are responsible for its toxic properties and tendency to trigger autoimmune reactions. However, the instabilities in M1 were not necessary for M1 to be effective as a vaccine. When injected into mice, stabilized M1 elicited a strong immune reaction that provided protection against infection with GAS bacteria.

“Stabilized M proteins may also last longer in the body than natural M proteins, which would be beneficial for vaccine development,” said Ghosh.

“However, a strep vaccine would have to cover many strains of strep, so stabilized M1 might be one of multiple stabilized M protein antigens used in a vaccine,” added Nizet.

Many of the greatest inventions in modern medicine were developed by physicists who imported technologies such as X rays, nuclear magnetic resonance, ultrasound, particle accelerators and radioisotope tagging and detection techniques into the medical domain. There they became magnetic resonance imaging (MRI), computerized tomography (CT) scanning, nuclear medicine, positron emission tomography (PET) scanning, and various radiotherapy treatment methods. These contributions have revolutionized medical techniques for imaging the human body and treating disease.

Now, in 2008, the American Association of Physicists in Medicine (AAPM), the premier scientific and professional association of medical physicists, is celebrating its 50th anniversary and is calling attention to the field of medical physics achievements.

“There are a number of ways in which medical physicists contribute to medicine,” says AAPM President Gerald A. White Jr. “Some develop cutting-edge technologies in the physics laboratory, while others are board-certified health professionals who apply these technologies in the clinic and help diagnose illness and alleviate suffering for millions of people a year in the United States.”

As a practicing medical physicist himself, White contributes to patient care at his practice at Colorado Associates in Medical Physics in Colorado Springs.

“Virtually all hospitals in the country today have medical physicists on staff to help administer radiation therapy treatment and to insure quality in both radiation treatment and imaging techniques,” says long-time AAPM member Jean M. St. Germain, who is the Acting Chair of the Department of Medical Physics at Memorial Sloan-Kettering Cancer Center in New York.

In the coming year, the AAPM will be calling attention to the many ways in which medical physics has revolutionized medicine. A few highlights include:

1. Using Particle Accelerators To Defeat Cancer

   In the last 50 years, medical physicists have spearheaded the development and application of particle accelerators for cancer treatment. Once confined only to physics laboratories, linear accelerators are sophisticated high energy machines that can now deliver beams of energetic electrons or X rays to malignant tumors — at doses capable of killing cancerous cells and stopping the tumor’s growth.

   In recent years, an advanced treatment technique called intensity-modulated radiation therapy (IMRT) has enhanced the ability of radiation to control tumors. IMRT uses computer programs to precisely shape the treatment field and control the accelerator beam in order to deliver a maximal dose of radiation to a tumor while minimizing the doses to surrounding healthy tissues. IMRT is already in use for treating prostate cancer, cancers of the brain, head and neck and other malignant diseases, in children and in adults.

2. Better Detection Of Breast Cancer

   Techniques for breast imaging have undergone substantial advances since the introduction of the original film techniques. The early emulsion films were replaced with more sensitive film stocks and finally with digital imaging. As each of these newer techniques was introduced, doses to the patient were reduced and the sensitivity of the techniques for finding early and treatable disease increased. Computer-aided diagnosis and the use of MRI and CT for breast imaging promises to further advance cancer detection and treatment in the 21st century. MRI breast imaging is proving particularly useful at finding growths in younger women and at earlier stages.

3. Matter/Antimatter Collision Imaging

   Another rapidly growing technique used to detect diseases in people of all ages is positron emission tomography (PET). This technique uses short-lived radionuclides produced in cyclotrons. These nuclides are labeled to compounds such as glucose, testosterone and amino acids to monitor physiological factors including blood flow and glucose metabolism. These images can be crucial in detecting seizures, coronary heart disease and ischemia. In cancer care PET imaging is used to detect tumors and monitor the success of treatment courses as well as detecting early recurrent disease.

   The actual imaging technique sounds like a science fiction movie — it involves matter and antimatter annihilating one another. The short-lived radionuclides decay and emit particles known as positrons — the antimatter equivalent to electrons. These positrons rapidly encounter electrons, collide, annihilate, and produce a pair of photons which move in opposite directions. These photons can be captured in special crystals and the images produced by computer techniques.

   Other techniques, such as radioimmunoassay, use the decay of radioactive materials to study a variety of physiological conditions by imaging or chemical methods.

4. Ensuring The Safety Of People Who Get CT Scans

   With the intent to promote the best medical imaging practices nationwide and help ensure the health and safety of the millions of people who undergo CT scanning each year in the United States, the AAPM issued a CT radiation dose management report in 2008, recommending standardized ways of reporting doses and educating users on the latest dose reduction technology. The report is available on the AAPM Web site. An associated news release can be accessed here.

5. Medical Physics Moments In History

   Some of the greatest medical advances in the history of medicine occurred in the past century and came from the minds and laboratories of physicists including:

   • X Rays
     Discovered by Wilhelm Conrad Roentgen in 1895, the application of these rays to medical imaging was recognized and embraced immediately. When the Nobel Prizes were established at the turn of the century in 1901, Roentgen won the first prize (in physics) for his discovery of X rays.

   • Magnetic Resonance
     Though Felix Bloch and Edward M. Purcell shared the Nobel Prize in Physics in 1952, just a few years after discovering the phenomenon of magnetic resonance, it took a few more decades before their discovery led to the development of MRI, which is routinely used today to image the human body. In 2003, the Nobel Prize in Physiology or Medicine was awarded to Paul Lauterbur and Peter Mansfield for their work in MRI.

   • Radioimmunoassays
     In 1977, the Nobel Prize in Physiology or Medicine was awarded to AAPM member Rosalyn Yalow for her the development of radioimmunoassays, an extremely sensitive diagnostic technique that can quantify tiny amounts of biological substances in the body using radioactively-labeled materials.

   • Computer-assisted Tomography
     In 1979, Allan M Cormack and Godfrey Newbold Hounsfield won the Nobel Prize in Physiology or Medicine for developing CT, which has revolutionized imaging because CT provides images with unprecedented clarity.

Thalidomide, a drug blamed in the 1950s for causing birth defects, is now showing promise as a safe and effective treatment for women with recurrent ovarian cancer, according to a study led by a University of Minnesota Cancer Center researcher.

Levi Downs, Jr., M.D., principal investigator for the multicenter, randomized Phase II clinical trial, has published the findings of this research study in the current issue of the journal Cancer. Downs is an assistant professor and a researcher of gynecologic oncology at the University of Minnesota Medical School and Cancer Center.

“For some women, ovarian cancer has become a chronic disease,” Downs said. “The standard chemotherapy regimens can put recurrent cancer in remission, often more than once. However, when the cancer resists the standard treatments, we need new options for treatment.”

The study compared the effectiveness and safety of the combination of thalidomide and topotecan, a chemotherapy often used for ovarian cancer, versus topotecan alone for treatment of recurrent epithelial ovarian cancer in patients who had received prior treatment. Epithelial ovarian cancer is a disease in which cancer cells form in the tissue that covers the ovary.

The study evaluated 75 women who were randomly assigned to receive either the combination of thalidomide and topotecan or only topotecan. This is the first randomized clinical trial to test thalidomide for recurrent ovarian cancer. Other clinical trials have shown thalidomide to be effective for treatment of multiple myeloma, a cancer of the bone marrow.

“We found that patients who received topotecan plus thalidomide showed an overall response rate of 47 percent compared to 21 percent response in patients who received only topotecan,” Downs said. “In patients receiving topotecan plus thalidomide, 30 percent achieved a complete response, meaning the cancer went away, compared to 18 percent for patients only getting topotecan.

“Furthermore, patients getting topotecan plus thalidomide had a longer cancer-free period after treatment than those receiving topotecan alone,” he said. “What all of this means is that while thalidomide may not cure ovarian cancer, it may broaden the treatment options available to physicians and provide more hope to women diagnosed with the cancer.”

Ovarian cancer is the fifth most common cancer among women. This year in the United States, more than 25,000 women will be diagnosed with ovarian cancer, and about 16,000 will die from it. About 78 percent of women diagnosed with the cancer survive one year after diagnosis, and more than 50 percent survive five years after diagnosis.

The results of this study have led to the development of a new clinical trial at the University of Minnesota that will test the safety and effectiveness of a newer member of the class of drugs containing thalidomide properties for treatment of recurrent ovarian cancer.

Overtaking on two-lane roads is easier if drivers use what is known as an overtaking assistant, a system which indicates when it is safe to overtake. This system prevents reckless drivers overtaking when it is not safe and can also aid cautious drivers in overtaking slower vehicles. This is the proposition of researcher ir. Geertje Hegeman, who will receive her PhD on this subject from TU Delft in the Netherlands on Thursday 28 February.

Each year in the Netherlands at least 25 deaths are caused by overtaking manoeuvres that go wrong. In many other countries, the statistics are much higher. Researcher Geertje Hegeman has designed a warning system (the overtaking assistant) which displays a green light when it is safe to overtake another vehicle. If it is not safe, a red light is displayed. She has tested this in a driving simulator on a two-lane road. Her conclusion is that the overtaking assistant increases the driver’s sense of ease and can have a positive effect on safety and efficiency.

Men And Women

Hegeman charted current overtaking behaviour by observing traffic on the N305 between Almere and Zeewolde in the Netherlands. The observed overtaking manoeuvres take an average of about eight seconds. Ten percent of the overtakers have fewer than three seconds between them and the oncoming vehicle. She used these observations to design the overtaking assistant, which has been tested in a driving simulator as well as using other methods.

One interesting aspect of the study conducted by Hegeman in the driving simulator is the differences in behaviour between men and women. Of the participating 12 men and 12 women, the women overtook more when driving using the assistant, while men in fact overtook less. This reduced the differences in driving behaviour between men and women. Furthermore, when using the assistant, men were less inclined to swerve to one side (they often do this to see whether there is any oncoming traffic), which is also beneficial to traffic safety.

Inter-Vehicle Communication

Hegeman’s overtaking assistant is not yet commercially available. Hegeman: ‘The required technology is still being developed. BMW’s top-range cars do carry a kind of inverted overtaking assistant which indicates when it is not safe to overtake. This is done with the aid of GPS; the system knows reasonably precisely when bends or hills are coming up. Chiefly due to a fear of claims, however, BMW does not yet dare to actively display a green light for overtaking.’

In addition to GPS, inter-vehicle communication between all vehicles is in Hegeman’s view needed in order to give correct overtaking advice. This is already the subject of a great deal of study (e.g. with a view to anti-collision systems), but according to Hegeman it could be another ten years before the first overtaking assistants are commercially available.

Eastern Europe

One advantage of the overtaking assistant compared to other solutions aimed at making overtaking easier and safer (overtaking bans or special lanes) is that the assistant can be used anywhere in the world. The benefits of the overtaking assistant could be particularly great in, for instance, East European countries which have many two-lane roads and relatively long, straight stretches of road.