In recent years, imaging technology has allowed physicians and surgeons to see the inside of the body as never before. Magnetic resonance imaging (MRI) creates a picture that can identify every structure, normal or not, within the field of interest. Now this technology is being taken into the operating room to help surgeons perform delicate surgeries, such as removing brain tumors more precisely. Intraoperative MRI, as it is called, is done in an operating room during an active surgical procedure. Traditional MRI machines are bulky and stationary. The new device is compact enough to be easily maneuvered around an operating room. This type of MRI was first used in Tel Aviv and Switzerland.
Dr. Ralph Dacey Jr., director of neurosurgery at Washington University, explains how it will help: “Intraoperative MRI will allow us to do high-resolution imaging during brain surgery. After removing a tumor, we can check the site with the MRI to determine if we missed any tumor that still could be safely removed.” Because MRI uses a strong magnet, having the machine in the OR creates some challenges, specifically around iron-based metals. A special operating room has been designed that will allow the presence of both the equipment and normal surgical tools. After surgeons have removed most of the brain tumor, the surgical field is isolated from instruments and other equipment that could interfere, and the MRI is pulled into place. After viewing the films in real time, the machine can be retracted, and the operation resumed.
“This is a regular-strength MRI with good imaging quality,” explains Dacey. “We will be starting to use this in February 2008, initially for brain tumors, but we plan to extend its use for tumors of the head and neck, the chest wall and liver. We’re one of only eight centers in the world where this is happening.” Surgeons are excited about the innovation, the MRI equivalent of the portable X-ray machine. It will allow them to view the images during the actual operation, rather than looking at films preoperatively and postoperatively, thus eliminating unnecessary second surgeries for patients.
In the 1970s, the average size of a kidney tumor was about 8 to 9 centimeters in diameter when it was first detected. Because of that, the whole kidney had to be removed. Today, thanks to advances in imaging, tumors average 3 centimeters when found, usually during a CT scan or MRI for another problem, since kidney tumors tend to have few symptoms. That early detection has made it possible to remove only the part of the kidney around the tumor, a partial nephrectomy, leaving most of the kidney functioning. It also makes it possible to perform the surgery laparoscopically, preventing the trauma of a large incision and other surgery complications.
Dr. Samuel Bhayani, urologic surgeon, is co-director of Robotic Surgery for the Washington University Institute for Minimally Invasive Surgery. “Kidney cancers are rare,” he says. “There are about 40,000 diagnosed per year, and the mean age of diagnosis is in the 50s and 60s. Instead of taking out the whole kidney for a pea-size tumor, we can now take out only the part with cancer and leave a functioning 75 to 80 percent of the kidney. It’s the kidney version of the lumpectomy. While people can function well with one kidney in the short term, long-term it’s not a great idea.” Barnes-Jewish Hospital is one of the worldwide leaders with expertise in this procedure. Bhayani is one of three or four experts in the world doing laparoscopic partial nephrectomies robotically, and he also teaches classes in its use.
He notes that when removing the entire kidney, 60 percent of patients will develop chronic renal insufficiency compared to only 15 percent with the partial nephrectomy. “It can prevent ending up on dialysis, and allows better control of hypertension,” Bhayani says.
He reports that even between early 2001 and 2002, 90 percent of tumors under 4 centimeters were still treated by complete kidney removal. The problem, he says, has to do with exposure and training. “There are about 10,000 urologists. The average urologist may see three or four kidney tumors a year,” Bhayani explains. “Training is tricky when you don’t have the opportunity to use it. During a partial nephrectomy, we have to stop the blood flow to the kidney, cut out the tumor quickly, reconstruct the kidney, restore blood flow and prevent bleeding. It’s a difficult skill through a large incision, and even harder laparoscopically. If it’s done robotically, the level of difficulty increases.”
For some epilepsy patients, the after-effects of a seizure can be as troubling as the seizure itself. One concern is the cognitive impairment that ensues afterward: memory loss, slowed reactions and reduced attention span. Prior studies had indicated that seizures damage dendrites, those tree-like extensions of nerve cells. Small bumps on the exterior of dendrites, called spines, are already known to be important to form synapses, or junctions that allow two nerve cells to communicate. A team of researchers led by Michael Wong, M.D., Ph.D., assistant professor of neurology, anatomy and neurobiology, observed this directly in laboratory mice.
“Previous studies had suggested that seizures were damaging the dendrite structure, but they couldn’t prove cause and effect,” Wong says. By applying a new technique, multiphoton imaging, Wong’s team tracked brain cell changes during artificially induced seizures. Within minutes of a seizure in a mouse, they found rapid changes happening to the dendrites. These became swollen, and the spines disappeared. After the seizure, the swelling gradually went down, but the spines didn’t return for 24 hours or more. Scientists think spines might be linked to something called long-term potentiation, a process that makes it easier for messages to pass between nerve cells and be encoded into memory.
Wong’s team also discovered that seizures were causing the breakdown of actin, a molecule used in cell structure. When they gave the mice the drug FK506 prior to inducing the seizure, they were able to block the breakdown. FK506 has been used in the past as an immunosuppressive drug, but in this case, they believe it inhibits enzyme pathways that break down the actin in cells. Seizures activate those enzymes. By blocking it ahead of time, they can prevent it. Researchers are looking for some variation of a drug that could be given to seizure patients after a seizure to prevent breakdown, rather than adding medication to what seizure patients already take on an ongoing basis.
Their next step is to define the pathways more specifically, along with how seizures break down structures. “Once we find all the molecules involved, we can hopefully find better drugs,” Wong says. “Current drugs treat the symptom of seizures but don’t attack the underlying cause, like aspirin does for a fever. We are looking at drugs with a curative application. That’s why animal studies are so important. And with our new multiphoton imaging technique, we can track the changes in real time in the mice and not have to determine the pathology by directly inspecting their brains.”
In Alzheimer’s patients, an abnormally folded protein, amyloid beta protein, is toxic and erodes cognitive function. By working with mice that have been bred with an animal version of Alzheimer’s disease, researchers have found a promising treatment in the form of an antibody, immunoglobulin M (IgM) class, that grabs onto the amyloid beta protein in the brain and prevents it from changing into the toxic substance thought to cause the disease. A single intravenous dose of IgM reversed learning impairment in aged mice with deficits similar to those found in Alzheimer’s patients.
Dr. William Banks, professor of geriatrics and pharmacological and physiological science at Saint Louis University and the Veterans Administration Medical Center, explains what they think is happening. “We know from neuroimaging that the hippocampus is important to learning andr memory. We find a lot of amyloid beta protein in that area and in the frontal cortex in Alzheimer’s patients,” Banks says. “In our mouse research, we found that when we injected the antibodies, the cognitive deficits in the mice got better, but we’re not sure why. Whether the harmful product is the strings or the plaque is debatable. But we know either way, if the IgM antibody is holding onto it, it’s better than having either free.” Banks and his team collaborated with Michael Steinitz from Hebrew University in Jerusalem, who developed a specific IgM antibody that sticks well to amyloid beta protein.
One of the most exciting aspects of this research is the effect after the IgM antibody is injected into the bloodstream. Normally, the blood-brain barrier keeps large, potentially harmful molecules away from the brain. The IgM molecule is a large one; in fact, it’s five times larger than the IgG antibody, which typically can’t cross the barrier.
“We know that IgG doesn’t get through this barrier very well, and when it does, it typically gets ushered right back out,” says Banks. “So why doesn’t the much larger IgM get kicked out? We think that when a molecule gets to a certain size, getting bigger doesn’t make much difference. We think both IgG and IgM get in by slow leakage, and when IgG leaks in, there is a specific transporter that recognizes the molecule and pumps it back out. That transporter doesn’t recognize IgM, so it gets to stay.”
Pregnancy Weight Gain
For more than a decade, obstetricians have followed The Institute of Medicine’s 1990 guidelines that suggest pregnant women should gain at least 15 pounds during pregnancy, with no upper limit cited. While that may be prudent for normal or underweight pregnancies, a new study indicates those guidelines put overweight and obese women at risk. In one of the largest population-based studies of pregnant women, researchers examined the pregnancies of more than 120,000 Missouri women to see how weight gain affected preeclampsia (high blood pressure brought on by pregnancy), Cesarean delivery and baby size.
“This study confirms what we’ve suspected all along—that obese women don’t have to gain any weight during their pregnancy,” notes Dr. Raul Artal, study author and chairman of obstetrics, gynecology, and women’s health at Saint Louis University and St. Mary’s Health Center. “Guidelines for nutrition during pregnancy at the time of the 1990 recommendations were based on expert opinion and not scientific data. Obesity has increased markedly since then.”
“Instead of the common conception that pregnancy is the time for taking it easy and eating for two, we have clearly shown that being active and not gaining weight—even losing weight during pregnancy—means much better outcomes for both mother and baby,” Artal adds. “Mothers have lower rates of complications, such as high blood pressure and gestational diabetes, and lower operative complications. Babies are born smaller and without the problems large babies often have. Besides eating well to limit weight gain, the positive effect can be amplified by adding exercise.”
The findings of the new study are significant in addressing the public health crisis of obesity. Artal says that if obese women gain weight during pregnancy, they will keep much of it and gain more in subsequent pregnancies. That’s compounded by the fact that how Mom eats and what Mom does affects the behavior and weight of the rest of the family. The Institute of Medicine is now looking at changing its recommendations.
Scientists know that people with heart and blood vessel disease tend to have problems with cholesterol, but they haven’t, until now, understood the connection between the two. A recent study indicates that cholesterol clogs arteries and blood vessels by suppressing the activity of a key protein that protects the heart and blood vessels. These recent study findings at Saint Louis University School of Medicine also could lead to new therapies to treat or prevent heart disease and other diseases associated with high levels of cholesterol, like some forms of cancer.
The study’s lead researcher and professor of biochemistry and molecular biology at Saint Louis University, Jung San Huang, Ph.D., says these findings represent a significant breakthrough in cardiovascular research. Using a mouse model, Huang’s researchers have found that cholesterol limits the activity of a key protective protein called ‘transforming growth factor-beta (TGF-beta).’ It protects the aorta and other vessels from damage caused by hypertension, high cholesterol and infection. Cholesterol, particularly low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) components, suppresses the responsiveness of the cardiovascular cells to TGF-beta, allowing atherosclerosis to develop.
“That’s why we call LDL and VLDL the bad cholesterol, and high-density lipoprotein (HDL) the good cholesterol,” notes Huang. “HDL enhances the function of TGF-beta. Cholesterol-lowering drugs, such as statins, also enhance TGF-beta cellular responsiveness.” Other therapeutic agents that enhance TGF-beta responsiveness include fish oils and other sources of Omega-3 fatty acids. Conversely, researchers also know that trans fats depress TGF-beta activity.
“Our findings have generated great interest in academic and pharmaceutical industry scientists and clinicians. What we have discovered should shape research efforts for years to come, and not only in cardiovascular disease,” Huang says. “For instance, we know now that TGF-beta also suppresses tumors in certain types of cancer, such as colon cancer, for which people with high cholesterol are at greater risk.”
Some genetic diseases that have brain involvement are extremely difficult to treat because of the blood-brain barrier, a mechanism that protects the brain and central nervous system from large, potentially hazardous molecules. Such is the case with Sly Syndrome, a rare genetic disease that causes bone defects, mental retardation, vision and hearing problems, heart disease and premature death. There are an estimated 100 people with Sly Syndrome in the U.S. Dr. William Sly, chairman of biochemistry and molecular biology at Saint Louis University School of Medicine, discovered the condition in 1969. He has been using what he learned from that and other similar genetic diseases to research how a potentially life-saving enzyme can be made to cross the blood-brain barrier to replace what the body doesn’t make on its own.
A number of lysosomal storage diseases collectively affect one in 7,000 live births, with 90 percent of them in some way affecting the brain. Each is missing a critical enzyme that must be replaced on an ongoing basis. These diseases cannot be cured, only managed, so Sly and his team are working on a way to deliver the missing enzyme through the bloodstream. “Our problem has always been the blood-brain barrier,” he says. “Some of the enzymes that need replacing are enormous, 1,000 times larger than a sugar molecule. We found that we could inject newborn mice with the enzyme and easily cross the barrier; but within about two weeks after birth, we could no longer do that. The newborn mouse has receptors on brain capillaries that recognize the enzyme and take it across, while adult brain capillaries have very few receptors. We have been trying to make the receptors in those capillaries come to the surface just as a newborn’s do and have found epinephrine does that.”
About 10 percent of the adult population suffers from chronic insomnia. That’s a greater percentage than those who have diabetes, a disease declared a national epidemic. Our bodies have an internal time clock that tells us when to be asleep and when to be awake. It takes its cues from, among other things, light. Experts note that insomniacs may unknowingly be making their problem worse. “Bright light lets our brain know that it is wake time. If we get up in the middle of the night with insomnia and decide to do some computer work or check our e-mail, we can negatively reset our internal clock,” warns Dr. Joseph Ojile, CEO and founder of Clayton Sleep Institute and medical director of St. Anthony’s Sleep Center. He says the problem is far from an insignificant complication to getting a good night’s sleep.
“We use bright light to help people reestablish their internal clocks,” Ojile says. “Those who have a delayed sleep phase, like teenagers who stay up late and then can’t get up in the morning, are treated with bright light for 20 to 30 minutes in the morning to let their bodies know this is awake time. Older people often develop an advanced sleep phase: They wake up too early and go to bed early in the evening, so we use light for them, too.”
But light becomes problematic, he says, when people are exposed to it at the wrong time, like when they wake up at night and get up to do something until they become sleepy again. If they decide to work on their computers, that can be a problem, Ojile emphasizes. Desktop computer screens emit a great deal of light, telling the brain it’s time to get up and starting a vicious cycle of insomnia.
“Anything you do that is stimulating puts off sleep longer and signals the body to be awake,” says Ojile. “The same goes for televisions in the bedroom. If the brain associates Jay Leno’s monologue with bedtime, it sets the brain up with the wrong cue. The cue to sleep should be the bed. That’s not to say you shouldn’t watch the show, but don’t do it in bed. Make your bed for sleep only.”
Ojile says it’s completely normal to wake up a couple times a night. What’s abnormal is not being able to go back to sleep in a couple of minutes or so.
Less Invasive Cosmetic Surgery
More women and men these days are opting for ‘less invasive’ cosmetic procedures earlier to head off major changes later. This strategy is effective and easier on the budget than major surgeries. The American Society for Aesthetic Plastic Surgery keeps track of these things. Since 1997, it has been collecting multi-specialty procedure statistics and has seen the number of cosmetic procedures increase 446 percent since then. In 2006, Americans spent just under $12.2 billion on cosmetic procedures: $7.6 billion for surgery, and $4.5 billion on nonsurgical enhancements. While it may seem like a lot of surgery is being done, that isn’t exactly the case, as surgical procedures are much costlier than nonsurgical ones.
Top surgical and nonsurgical cosmetic procedures combined for men and women in 2006 are:
There were some notable differences between men and women in 2006. The top surgical procedure for women was breast augmentation, while for men, it was liposuction. Botox led the list for both men and women for top nonsurgical enhancement, with women’s procedures outnumbering men’s 9,590:1.
Because cosmetic procedures can be very pricey and are not covered by health insurance, patients are looking at getting the best results for the least amount of money. While a face-lift is good for 10 years or more, the initial outlay of $6,298 can be more than the budget can handle—and that’s only the surgeon’s fee. Add in a surgi-suite, anesthesia and adjunct therapies, and the cost can more than double. Botox for those frown lines between the brows, a chemical peel and filler, while these may have to be repeated, comes to about $1,750 combined.
Cosmetic surgeons are accustomed to sitting down with clients to work out the most effective way of dealing with what bothers them, and doing it within their budget. Often the surgeon will come up with a progressive program to fix one problem first, and then do another procedure the next year.