|February 2000 |
Scientists find new understanding of Alzheimer's risk factor
While scientists have known for a number of years that some forms of the high-density lipoprotein apoE can increase a person's risk of developing Alzheimer's disease at an early age, until now, they have not known why. Researchers at the Washington University School of Medicine, working with mice, showed for the first time that apoE contributes to neuritic plaque development in the brain. Neuritic plaque, containing fragments of dead and dying neurons and the protein amyloid-beta, is considered a hallmark of the disease.
Body fluids normally contain low levels of the protein fragment amyloid-beta. While amyloid-beta deposits dot the brains of Alzheimer's patients, this study showed the deposits do not hurt the brain. This research found that the animal's brain cells were harmed when apoE prompted the amyloid to form hair-shaped fibrils and neuritic plaque. The scientists found apoE4 caused more damage than apoE3. The study was reported in the March 14 issue of Proceedings of the National Academy of Sciences. About 40 percent of all late-onset Alzheimer's patients have the apoE4 gene, with those lacking a family history of Alzheimer's more likely to have it. "To me, these results strongly suggest that the main reason that apoE4 is a risk factor for Alzheimer's disease is because it interacts with amyloid-beta protein and enables it to become fibrillar, which in turn promotes neurodegeneration," said lead author David M. Holtzman. The researchers hope to use this information to develop pharmaceutical treatments.
"We believe it may be possible to alter the levels of brain apoE with drug therapy," said coauthor Dr. Steven M. Paul, with Eli Lilly and Company. "Such drugs should inhibit the deposition of amyloid-beta, prevent fibril formation and promote amyloid removal, which would have the potential to slow down or even prevent Alzheimer's disease."
Ultrasound technique may replace blood tests
Maintaining optimum blood sugar control and minimizing life-threatening complications requires that diabetics check their blood sugar levels at least four times a day. But sticking fingertips with a lancet often produces sore digits. A new method, which could render blood testing obsolete, uses noninvasive, painless ultrasound technology to determine glucose levels. A single, low-frequency ultrasound application increases skin permeability for 12 to 15 hours, allowing fluids, which surround cells, to cross the skin for measurement. In a study reported in Nature Medicine, researchers using ultrasound technology collected nine samples, over a four hour period, from the forearms of seven type 1 diabetics, then compared the results with subjects blood glucose levels. "We took blood from one arm of the patients to just be sure our new method had the correct results. Both methods had almost the identical readings," said coauthor Dr. Robert Gabbay, at Penn State's College of Medicine. "We hope that by developing this new painless method for measuring blood glucose we can help patients achieve better glucose control."
Larger clinical trials are planned. Researchers expect a portable glucose-monitoring device, in the price range of current meters, will be available in three to five years. Possible features include a sensing patch that will display glucose concentration and sound an alarm if levels reach unsafe levels. Because previous research has shown insulin can be administered using similar technology, researchers speculate that a wristwatch- or patch-like device, could be developed to monitor glucose levels and deliver insulin. But the ultrasound technology is not limited to diabetic care. "We're hopeful that this could eventually be a universal way of noninvasively sampling a variety of substances from humans," said coauthor Robert Langer, at Massachusetts Institute of Technology. "Blood tests for any number of things, such as cholesterol and bilirubin, could someday be replaced with this technique.
Body "wear and tear" linked to education and hostility levels
What do schooling and anger have to do with health? Scientists at Harvard's School of Public Health say hostile men with less education show signs they tax their physiological systems more than their mellow, more-learned counterparts, which bumps the angry group's risk for poor health.
As part of its normal functioning, the body increases blood pressure and changes hormone levels when exposed to stress and negative emotions. As the perceived threat subsides, body systems return to normal, but frequent angry outbursts or emotional stews fire up successive responses, increasing physical wear and tear, or "allostatic load." "Our results suggest that repeated stresses, such as those associated with lower (socioeconomic status), may trigger psychological factors such as hostility. In turn, hostility may increase wear and tear on the body directly through physiological activity or strain, or indirectly through health behaviors such as smoking," said lead author Laura D. Kubzansky, Ph.D., of the university's Department of Health and Social Behavior.
During the study, reported in the Annals of Behavioral Medicine, researchers assessed 818 white, Boston-area males, ages 21 to 80 years, participating in the onging Normative Aging Study, which began in 1961. For this research, the team checked blood pressure, abdomen-hip ratios, cholesterol and glucose levels, and urinary norepinephrine and epinephrine excretion. Researchers compared these wear-and-tear measurements with participants' feelings toward others, cynicism, negative emotions, angry or aggressive responses to certain situations, and general behavior, as well as education level, which they used to gauge socioeconomic status.
Men with less than a high school education had significantly higher allostatic load than men with at least a college education. Researchers caution the results may not hold true for women or non-white populations.
Do-it-yourself glaucoma test developed
Imagine the fear of living with a disease that can steal your vision, and the relief of knowing your diligent self-care efforts are keeping the danger at bay. That futuristic, high-tech possibility is about to become reality thanks to a new, inexpensive glaucoma test developed by Yale School of Medicine physician Dr. M. Marc Abreu.
The simple, painless Alcon Abreu Tonometry System may soon bring peace of mind and improve compliance with sight-saving medicines. The completely automated system can measure eye pressure in about 0.01 seconds and, unlike traditional tests, does not require any anesthetizing eye drops. Patients wear a disposable contact lens with a magnetic strip which lets a small palm-size device electromagneticly measure pressure in the eye and send the results over the Internet to the doctor's office. The device may yield more accurate results than traditional in-office tests, because it does not prompt involuntary movements, which occur with tests that briefly touch the eye while taking a measurement.
"The device is planned to provide the doctor with a whole history of pressure changes when the patient is not in the doctor's office," Abreu said. "Furthermore, the doctor can set the target eye pressure for each patient and, in this way, better monitor treatment."
Patients will be able to test their eye pressure as often as they want. Abreu expects the device will increase patients' awareness of their condition and increase medication compliance. "There is the potential to completely change the way glaucoma is treated, diagnosed and monitored," said Abreu.
Approximately 3 million Americans suffer from glaucoma, many unaware they have the disease until permanent damage has occurred. A leading cause of blindness, glaucoma causes pressure to build in the eye, which damages the optic nerve. Genetics, aging and steroid use increase risk.
Presence of gene may indicate need for more aggressive colon cancer treatment
Sometimes scientific research takes unexpected turns, unlocking mysteries and offering new methods for improving patient care. Such was the case for a team of Cedars-Sinai Medical Center doctors who discovered a gene that triggers tumor growth in the pituitary gland also appears in colorectal tumors and precancerous polyps likely to turn malignant. The discovery, reported in Lancet, may change colon cancer treatment strategies. Aggressive tumors express higher levels of the Pituitary Tumor Transforming Gene (PTTG1). If doctors can determine whether a high level of PTTG1 exists during colonoscopy or surgery, they can order more aggressive therapy. The gene might also be used to monitor a patient's response to treatment.
"This is how serendipity finds its way into science," said senior author Dr. Shlomo Melmed. "We aren't oncologists, we aren't colon cancer scientists, we're endocrinologists who were looking at the pituitary when we found this gene. By chance, we were able to find it in other tumors as well."
Low levels of PTTG1 are found in most human tissue. Colon cancer cells and pituitary tumors express high amounts. The team discovered PTTG1 disrupted normal cell replication and activated a growth factor that prompted formation of new blood vessels, which nourish tumors. PTTG1 acts early in the malignant process and seems to push normal cells into turning cancerous. The scientists studied 68 colorectal tumor samples, 48 malignant and 20 colonic polyps. Every carcinoma expressed high levels of PTTG1, as did 19 of the 20 polyps. PTTG1 levels were significantly higher if the cancer had spread to the patient's lymph nodes or liver than when the cancer was confined to the bowel wall. Tumors with more blood vessels, meaning they are primed for growth, also had higher PTTG1 expression.
Oral vaccine protected rats from suffering a stroke
A newly developed oral vaccine protected rats from strokes' and seizures' adverse effects. Scientists say the drug shows potential for preventing seizures and their adverse effects, and protecting against the damage caused by stroke in humans. The vaccine prompts the body to develop antibodies that block a key brain protein from causing damage.
Jefferson Medical College researchers gave approximately 100 rats an antibody targeted at the brain protein the N-methyl-D-aspartate, which is involved with learning and memory, and in cellular events precipitating brain cell death after a stroke, severe seizures and other brain injury. One month later, scientists gave a group of the rats a neurotoxin known to cause seizure activity and saw dramatic protection. Scientists expected seizures in about 70 percent of the rats, but only 20 percent of the immunized rats experienced a seizure. In a second group of nine rats receiving a different vaccine, two developed seizures, but the vaccine seemed to protect one of the brains from cell death. Five months after immunization, scientists induced strokes in another group of rats and found a 70 percent reduction in brain damage. The vaccine caused no behavioral changes in the animals. The research was reported in the journal Science.
The team will continue investigating experimental vaccines and their ability to work for other conditions, including ALS, Parkinson's disease, depression and pain. They also plan eventual human trials, possibly with antibodies rather than vaccines due to a vaccine's potential for causing long-term, irreversible effects. "We would probably start out giving this to patients during bypass or other surgical procedures when their brains are at risk of stroke. Once we show that works, we can move on to other more severe diseases such as AIDS dementia, and eventually back to people at chronic high risk for stroke, such as those with high blood pressure or carotid stenosis," said lead researcher Dr. Matthew During.
New technique improves mammogram image
A new x-ray technique, developed at the University of North Carolina at Chapel Hill, has produced significantly improved images of breast tissue. Diffraction enhanced imaging, or DEI, places a silicon crystal in the x-ray beam between the patient and the film or another image-creating medium. Based on the physics principle Bragg's Law, the crystal diffracts x-ray wavelength. The final product combines an image similar to a standard x-ray with the new refracted picture, resulting in a more sensitive representation of the density differences between cancerous and normal tissue. "The images we have, which are the first to be published using this new DEI technology, are just spectacular," said co-lead author Dr. Etta Pisano. "Once we've overcome some technical challenges and adapted it for clinical use, DEI conceivably could be used not only in breast imaging, but in any medical and nonmedical application involving X-rays. The sky's really the limit."
The researchers created images of seven breast cancer specimens using conventional digital x-ray equipment and the new DEI technique and compared the results. In six of the seven specimens, tumors were more visible with DEI. Pathology reports confirmed the results, finding DEI's additional detail showed real structural information about the tumors, not technique-generated artifacts. The results were reported in the journal Radiology.
DEI requires a synchrotrons machine, which creates electromagnetic radiation by speeding up atomic particles. Before DEI can become a practical diagnostic tool in clinical practice a more portable device will need to be developed. "If the next phases of our work are successful, then in 10 to 20 years, it is possible that almost every X-ray imaging apparatus in the world would be replaced by a DEI apparatus," said the other lead author Dale Sayers, at N.C. State University.
New drug designed to treat mad cow illnesses
National Institutes of Health researchers have discovered a new class of compounds that slow prion disease development in mice. When infectious prion proteins change shape and collect in the brain, they slowly destroy nervous system tissue, causing mad cow disease in bovines and Creutzfeldt-Jakob disease (CJD) in humans. The new compound blocks the protein from folding incorrectly, stopping the disease. Previous research had shown cyclic tetrapyrroles, found in some cancer drugs, prevents proteins from changing shape in a test tube. Now National Institute of Allergy and Infectious Diseases scientists have shown cyclic tetrapyrroles can halt development of prion disease in mice.
In a study reported in the journal Science, researchers injected mice with high doses of scrapie, a diseased sheep prion protein that causes normal prions to change to the destructive form. At different times during the 80 day incubation period, scientists gave groups of mice one of three treatment compounds. Mice receiving a treatment compound at the same time or mixed with the infectious agent lived significantly longer than mice receiving the drug later in the disease process. The scientists concluded that the treatment may be helpful if given prior to or shortly after infection occurs. The compounds also might make blood products safer by inactivating infectious prions. "Since diagnosis of CJD in humans can be made only after symptoms appear, we are trying to identify a compound that works later in the disease," explained Suzette Priola, Ph.D. "The extremely wide variety of these compounds available for testing makes our current search for one that can affect disease after the onset of symptoms much more promising."
Similar collections of misfolded proteins, not involving prions, occur with Alzheimer's disease and type 2 diabetes. The scientists said drugs that block the folding process may be useful in treating those diseases.
Immune system chemical predicts heart problems
Recent studies have shown a link between inflammation or infection and plaque buildup in the arteries, or atherosclerosis. London researchers have discovered elevations of the chemical neopterin, produced by the immune system, may predict a worsening of coronary artery disease symptoms.
The scientists studied 114 women admitted to the hospital with angina, monitoring episodes of chest pain, heart attacks and other adverse cardiac events, and neopterin levels, over a one year period . At the start of the research, 82 women had chronic stable angina, experiencing chest pain after exercise or exertion that was relieved by rest. The balance had unstable angina, suffering chest pain at rest in the 48 hours proceeding the start of the study. Unstable angina is associated with a deterioration in a patient's coronary artery status.
Subjects with unstable angina had higher levels of neopterin and were twice as likely as those with stable angina to suffer a heart attack or other acute exacerbation during the study period. Those admitted to the study with stable angina but suffering a heart attack or other adverse cardiac event during the research period experienced elevations in neopterin that were similar to levels found in subjects with unstable angina. Researchers noticed an increase in adverse cardiac events as neopterin levels rose. Neopterin levels were not associated with white blood count or the number of diseased arteries. The study was published in the journal Heart.
The authors said their results add support for the theory that inflammatory processes and immune activation contribute to acute coronary events. They concluded that high neopterin levels indicate a disease progression rather than the extent of a patient's coronary atherosclerosis. Previous research has shown a connection between neopterin levels and peripheral vascular occlusion and carotid atherosclerosis.
Genetic link found for orthostatic intolerance
More than 500,000 people in the United States suffer from orthostatic intolerance. When they stand up after sitting or lying down, their heart rate increases by at least 30 beats per minutes. They experience nausea, headaches and dizziness, and may even faint. Researchers have found a genetic link to the disorder, offering insight into the condition's cause and treatment possibilities. "The discovery of this gene defect may lead to new understanding of blood pressure control and how extreme fluctuations in blood pressure can cause irregular heart rhythms," said Dr. Claude Lenfant, director of the National Heart, Lung, and Blood Institute, at the National Institutes of Health (NIH).
Normally, the autonomic nervous system adjusts heart rate and blood pressure to compensate for gravitational pull when people change position. Scientists have found people with orthostatic intolerance have high blood levels of the neurotransmitter norepinephrine, which is primarily involved with constricting blood vessels. Prior research has focused on changes in the chemical's release, but Vanderbilt University Medical Center scientists took a different approach. "If norepinephrine is high, there are really only two explanations -- either a lot more is being released from neurons or a lot less is being cleared away," said Dr. David Robertson, of Vanderbilt's Clinical Research Center. "When we looked, we found that there was reduced norepinephrine clearance in a significant percentage of patients with orthostatic intolerance."
Not all patients with orthostatic intolerance have the gene mutation, indicating additional causes exist. The scientists will start looking for other genetic mutations. The discovery is the first neurotransmitter transporter genetic defect linked with a human disease. The NIH-funded study was reported in the New England Journal of Medicine. "It focuses our understanding of this disorder in a new direction and shifts our attention for treatment options to entirely different kinds of drugs," Robertson said.
Calling 911 aids stroke victims
Powerful clot-dissolving drugs can save stroke victims lives and minimize brain damage but, because the drugs must be given within three hours of the onset of symptoms, few patients receive the treatment. Patients or their family members who called 911 arrived at the hospital by ambulance an average of one hour sooner and were more likely to receive the life-saving drugs, according to a new study conducted by researchers at the University of North Carolina at Chapel Hill. "We're trying to find out the reasons for the delays so that we can develop education programs or systems that can get people in quicker, so they can get this therapy," said Dr. Wayne A. Rosamond, with the University's School of Public Health.
Patients who had someone with them when symptoms started, younger patients and those who felt their symptoms were urgent were most likely to access emergency medical services (EMS). "The bottom line is that programs to promote the use of EMS for stroke should consider targeting not only people at risk, but also people around them such as spouses and older children," Rosamond said. "Everyone needs to know that stroke should be treated as an emergency."
However, people who had access to health information and knew about strokes did not call 911 any more often than other patients. Researchers compiled the information after briefly interviewing stroke patients or their family members, as they arrived at the hospital. About half the 617 patients could speak for themselves. On average, patients arrived at the emergency room four hours after symptoms began but many waited six or more hours. Symptoms include left- or right-sided weakness or numbness, sudden vision loss or incoherent speech. "We're trying to get people to understand that since stroke is a very serious medical condition, 911 should be involved immediately," Rosamond said.
New test for earlier detection of clogged heart arteries
Seeking a better method of diagnosing coronary artery disease, a Johns Hopkins University undergraduate and his advisors have developed a new noninvasive process for detecting when a heart starts weakening because it is not receiving a sufficient blood supply, a condition called myocardial ischemia. Diminished blood supply causes irregular cardiac electrical signals, but a typical electrocardiogram (ECG) will not always pick up small changes. The new computer-assisted method analyzes the ECG signal in a different way. "The whole idea is to detect the ischemia prior to the point where the damage is irreversible," said twenty-two year old student Mahesh Shenai. "If it's detected early enough, proper intervention steps such as drug therapy, an angioplasty or cardiac bypass surgery can be taken to restore the heart to a healthy condition."
Shenai adopted a math formula, called Wavelet Transform, that has been used in industrial settings. By analyzing turbulence in the ECG signal, he was able to detect areas of the heart with diminished blood supply. The researchers have tested the method on living laboratory tissue and on angioplasty patients, before and after the procedure. The ischemic changes picked up by the new analysis disappeared after doctors reopened the clogged arteries. Additional study and refinement is needed before the process can be used in emergency rooms or doctors offices. The research was reported in the Journal of Biological Systems.
"A regular ECG doesn't always detect signs of ischemia," said research associate Boris Gramatikov, Ph.D. "So a patient may come to an emergency room with chest pains and then be sent home. But one in 20 of those who are sent home will develop a heart attack. So any new tools we can provide to identify heart problems at an early stage could have some impact."
Gene transfer boosts heart function
Gene therapy offers hope of improving a common, age-related functional heart abnormality, according to researchers at Massachusetts General Hospital who have been working with rats. With age, hearts often lose the ability to relax between beats, a condition called diastolic dysfunction. About 40 percent of adults over 60 years of age suffer from the condition, which sometimes leads to congestive heart failure. "As our population continues to age in the coming years, we know we're going to be seeing more and more people with heart failure, which already is the most frequent cause of hospitalization in people over 65 in this country," said senior author Dr. Roger Hajjar.
Researchers boosted cardiac function in aging rats by transferring additional copies of the key gene SERCA2a into the animals' heart muscles. The SERCA2a protein causes calcium, needed by heart muscle cells during contraction, to return to its normal storage area. Two days after receiving the gene infusion, the aged rats experienced significantly improved, but not completely normal, diastolic relaxation. Untreated aged rats, that underwent a similar procedure without receiving the gene, showed typical age-related impairments. The results were published in the journal Circulation.
"Currently treatment options for diastolic dysfunction are very limited," Hajjar said. "These results suggest possible avenues for treating this very significant problem that results from the aging process itself, rather than from a specific disease."
Previous research has shown that additional SERCA2a gene expression could improve heart function, but this is the first study to show the SERCA2a gene might be useful in treating age-related diastolic dysfunction. Therapies might include new drugs to alter functions controlled by SERCA2a or new, safer methods of delivering gene therapy. Hajjar said additional research is needed to verify the results and cautions the technique may not offer the same benefits to people.
Gene therapy used to develop monthly antihypertensive
Working with rats, University of Florida (UF) researchers employed gene therapy techniques to create a new medication that safely lowers blood pressure for up to a month. The doctors say a monthly treatment regimen will benefit patients who do not take traditional drugs due to side effects.
The new injectable drug works by manipulating a fragment of DNA that sends genetic instructions making the body produce receptors where potentially harmful hormones connect to the heart and kidneys. Scientists refer to the DNA message as sense and the new class of drugs, reversing the message, as antisense. The genetic blood pressure medication, called beta1 antisense oligodeoxynucleotide, lowers blood pressure by decreasing the heart's ability to contract. Beta blockers, traditional drugs used to treat high blood pressure, inhibit the action of specific hormones, which also results in less forceful heart contractions.
The university's blood pressure drug did not alter the rats' heart rates or cause changes to their central nervous systems. Additional research is needed to determine if it produces problems in other body systems or causes long-term complications. UF researchers plan to test the blood pressure drug in humans after forming a pharmaceutical company association. The research was reported in the journals Hypertension and Circulation.
"The results look promising for a new way to treat hypertension with a drug that is so specific it will have few side effects, and so long-lasting that it would control blood pressure very well, without the need for daily medication," said investigator Dr. M. Ian Phillips. "This is going to be a new type of medicine, part of a completely new class of medicines called antisense."
It will not be the first antisense drug. In 1998, the Food and Drug Administration approved the antisense drug Vitravene to treat cytomegalovirus infections in the eyes of AIDS patients.
Diabetes drug may help prevent potential heart condition
The heart disease lipotoxicity occurs in obese rats when fat droplets collect in heart cells causing cell death. Scientists at the University of Texas Southwestern Medical Center fear the same process may occur in overweight humans. "This cell death in the heart is a consequence of the presence of more fat than is required for producing energy," said coauthor Dr. Roger Unger.
Fat buildup occurs in humans as part of the aging process, but researchers believe obesity causes it to happen at an earlier age, especially in overweight people who do not exercise. The team previously reported that the hormone leptin, found in greater quantity in obese subjects, caused insulin-producing pancreatic cells to die, resulting in type II diabetes. Working with genetically engineered obese rats, the researchers found fat collecting in the heart killed those cells, just as it did pancreatic tissue. As cells die, the heart cannot pump effectively and develops cardiomyopathy, which can lead to failure. The drug Troglitazone, used to treat diabetes mellitus, prevented the loss of cardiac function by oxidizing fat, making it burn up rather than accumulate. The results were published in Proceedings of the National Academy of Sciences.
"This damage occurs fairly early because, unlike other organs, the heart has a finite number of muscle cells; they can't proliferate," said study coauthor Dr. Paul Grayburn. "Even if you lose only 20 percent of the myocytes (heart cells), irreversible damage occurs, and cardiomyopathy will develop."
The researchers are working with university colleagues to develop a way of using magnetic resonance imaging to test for and measure the amount of fat in people's heart muscle. "Because this is a completely preventable condition in the obese rats, I believe it is urgent to find out if this happens in humans," Unger said. "If it does, we may already have the drug to treat it."
Exercise offers heart benefits in absence of weight loss
Moderate exercise can cut heart attack risk, improve cholesterol levels and decrease body fat percentages in moderately obese people, even if the activity does not result in weight loss. "Physicians have always recommended exercise, but there has been no real scientific basis on how much and how intensely one should exercise," said Duke University Medical Center cardiologist Dr. William Kraus. "This study shows that starting a moderate exercise program of only three months' duration -- even in the absence of weight loss -- can have significant beneficial effects on cardiovascular risk factors in overweight people with elevated cholesterol levels."
During a three month pilot study, seven men and women, who had a body mass index between 25 and 35, exercised with increasing intensity, using a treadmill, stationary bike, stair stepper and other equipment, for approximately one hour, four times a week. To determine exercise benefits without weight loss, researchers altered participants' diets, so they would maintain the same weight. Patients' LDL cholesterol, the bad variety, dropped on average from 122 to 104 mg/dL, and HDL cholesterol, the healthy kind, increased on average from 32 to 37 mg/dL. Participants' body fat decreased 4.3 percent and exercise tolerance increased 11 percent. The results were published in the journal Clinical Exercise Physiology. The National Heart, Lung, and Blood Institute granted Duke $4.3 million for a larger trial, which Kraus expects will confirm the pilot study's results.
"We now have the data for physicians who can tell their patients that they shouldn't focus so much on the scale," said Kraus. "These patients should not become discouraged and give up exercising, because our study shows that these patients are getting healthier even if they don't lose any weight."
Breast cancer recurrences caused by cells not removed during surgery
Recurrences of early stage, noninvasive breast cancer of the milk ducts may result from residual cells not removed during breast-conserving surgery. University of California, San Francisco researchers found a genetic link between original ductal carcinoma in situ (DCIS) tumors and cancerous growths that developed in remaining breast tissue an average of 4.2 years later.
Doctors consider lumpectomy typically followed by radiation the standard treatment for DCIS. But depending on the treatment received after surgery, five to 25 percent of the patients suffer from a breast cancer recurrence. Only one to two percent of DCIS patients who have a mastectomy experience recurrences. "The question was, 'Are the tumors really coming back or are the women who have preinvasive cancer more likely to have a different tumor in the same breast or in the opposite breast?'" said lead author Dr. Frederic Waldman.
The scientists, using a powerful molecular tool called comparative genomic hybridization, examined DNA from eighteen patients' original tumors and from growths found 16 months to nine years later. "We used genetic technology to define a genetic signature of each lesion and compared that to the genetic signature of each patient's own recurrence," Waldman said.
In seventeen women, chromosomal changes were similar between the original and second tumors, leading researchers to conclude that the subsequent tumor most likely grew from cancer cells left in the breast tissue after surgery. One patient had a new, unrelated growth. The authors said the results emphasize the importance of making wide surgical margins to remove all cancer cells and postoperative radiation therapy. The Journal of the National Cancer Institute will publish the study in its February 16, 2000 issue.
"This is an important confirmation that these recurrences are the same tumors, sitting there quiescent and coming back at a much later time.," Waldman said.
Thyroid disorder increases older women's heart risk
Dutch researchers report subclinical hypothyroidism puts older women at risk for heart attacks and hardening of the arteries (atherosclerosis). In a subclinical case, there are no symptoms and the pituitary gland produces extra TSH (thyroid stimulating hormone), prompting the thyroid gland to increase production.
Doctors studied 1,149 postmenopausal women and found 10.8 percent had subclinical hypothyroidism, a rate consistent with previous estimates. Researchers compared women with subclinical hypothyroidism with those who had normal functioning thyroids, testing for clinical signs of aortic atherosclerosis and heart attack, and evaluating medical records related to heart attacks suffered after the study's commencement. Both sets of women were similar in age, size and smoking status, and had comparable blood pressure readings and other lab values, but the women with subclinical thyroid function had lower total and HDL cholesterol levels.
Researchers discovered the women with asymptomatic, underactive thyroids suffered from more atherosclerosis and heart attacks, and concluded that subclinical hypothyroidism contributed to 60 percent of the heart attack cases in women with the condition and 14 percent of all cases. The authors said the risk percentage was similar to other major cardiovascular risk factors, such as high cholesterol, high blood pressure, smoking and diabetes mellitus. The study was published in the Annals of Internal Medicine.
Previous studies have linked overt, or symptomatic, hypothyroidism with an increased incidence of cardiovascular disease and have shown that the condition increases homocysteine levels, the likelihood of clot formation and blood viscosity. The authors theorize that the subclinical disease may produce similar changes, contributing to the increase in cardiovascular disease. Additional research is needed to determine the mechanisms occurring in subclinical hypothyroidism as well as the effectiveness of therapies, and if screening older women for the condition would prove beneficial. A simple blood test can determine a woman's thyroid levels.
Test using folate may help detect ovarian cancer earlier
A new diagnostic test for ovarian cancer may help doctors discover the disease earlier and more accurately evaluate its progress. Frequently called a silent killer, ovarian cancer often grows undetected, with only a quarter of the 23,100 cases diagnosed annually in the United States found before the cancer has spread. Doctors at the Indiana University School of Medicine are evaluating a new diagnostic procedure, called FolateScan, that uses a radioactive imaging agent attached to the B vitamin folate, also called folic acid.
Cells need folate to divide. Rapidly growing cancer cells, such as ovarian, require large amounts of the vitamin and send out special receptors to increase folate intake. Therefore, folate attaches more easily to those cells than to normal tissue. After injecting the radioactively tagged folate, doctors scan the woman's abdomen and watch for highlighted areas, which would indicate a malignancy. Knowing if an ovarian tumor is cancerous helps doctors determine if special techniques will be needed to completely remove the cancer during surgery. In addition to identifying cancerous lesions,the test may help determine if the cancer has spread to other areas within the abdominal cavity, assess effectiveness of treatments and monitor for recurrences.
The Purdue University associated biotechnology company Endocyte developed FolateScan. If the clinical trial proves successful, the test could be available for general use in two to three years. "FolateScan may lead to new methods for treating ovarian cancer," said the school's Dr. Greg Sutton. "If scanning proves successful, it may be possible to link radioactive or chemotherapeutic agents to folic acid in order to deliver these effective treatments directly to tumor cells."
Sleep apnea may signal hypertension
According to new research published in one of the American Lung Association's publications, the American Journal of Respiratory and Critical Care Medicine, sleep breathing problems often give away high blood pressure trouble. The study, which analyzed 1190 sleep disorders patients in a German clinic found that the more severe the sleep apnea symptoms, the greater the risk of hypertension, regardless of other contributing factors to elevated blood pressure, such as age, obesity, cholesterol levels, or alcohol/nicotine consumption. Interestingly, while about half of the test group (591) had no previous diagnosis of hypertension, about 72% of them tested positive for a sleep-related breathing disorder (SRBD), and nearly two thirds (61%) of them were diagnosed with high blood pressure during the study. Among the other half of the group (599) with confirmed hypertension, about nine tenths (89%) of them also suffered from SRBD. Moreover, researchers found that the link was most dramatic among sleep disorder patients under the age of 50.
While it's not exactly clear yet how SBRD hinges on hypertension, Norman Edelson, M.D., a spokesperson for the American Lung Association, explains that the link isn't a stretch. "In SRBD, the pharynx narrows briefly during sleep, causing a reduction in the level of breathing or even a momentary cessation of breath. The diminished breathing causes oxygen levels in the blood to drop which, in turn, increases the activity of the sympathetic nervous system - including a rise in blood pressure", outlines Edelson. But experts are concerned about more than the occasional snoring. "It's the fact that if sleep apnea is chronic enough, it can translate into high blood pressure that persists during the day, putting people at risk of heart disease". The study authors suggest that those with SBRD should have their blood pressure monitored, and hypertensives should be clinically assessed for a possible sleep disorder connection.
Tests may make more patients eligible for stroke treatment
"The method looks as though it will let us identify patients who still have salvageable brain tissue, in whom we might be able to recover brain function," said neurologist Dr. Argye Hillis. "In some patients the amount of brain that's died is tiny, but they still have huge problems, for example, in comprehension or speech. Those are the ones who may be helped, and they don't always fall right within the three hour limit." The team plans further study to quantify how long tissue remains salvageable. Brain function has been known to return as long as a week after a stroke.
Study finds cholesterol-lowering drugs underprescribed
High levels of cholesterol increase the risk of cardiovascular disease. Multiple clinical trials have shown statin drugs, such as Zocor and Pravachol, can safely reduce cholesterol levels and decrease the risk of heart attack and death from multiple causes, yet many doctors at major teaching hospitals do not order the drugs for their patients. In addition, new research shows doctors order statins more often for men than for women. Researchers at the University of Maryland Medical Center investigated how doctors treated 825 men and women at 16 U.S. and Canadian academic medical centers from 1994 to 1997. In about half the participants, LDL cholesterol (the bad type) was dangerously high: above 130 mg/dL. By the end of the study doctors had increased use of the drugs for men but prescribed them less frequently for women. "In general, treatment rates for patients with a history of heart disease were far too low, but the lack of adequate treatment in women was particularly worrisome," said lead author Dr. Michael Miller, director of Preventive Cardiology.
In 1994, doctors ordered cholesterol-lowering drugs for 42 percent of the men and 38 percent of the women with elevated LDL. Three years later, they found 54 percent of the men had received the medication but only 35 percent of the women. Thirty-one percent of male participants but only 12 percent of the women achieved the National Cholesterol Education Program's LDL goal of 100 mg/dL. The study was published in the Archives of Internal Medicine. "We don't know why women were so under-treated compared to men, especially since the extent of heart disease was similar in both groups," Miller said. "These results provide evidence of considerable sex bias in the treatment of women with heart disease at major academic medical centers."
Free radicals underlie alcohol related organ damage
According to a study published recently in the Journal of Clinical Investigation, repeated alcohol consumption has been linked to the formation of free radicals, which are responsible for the lasting organ damage that results. University of Pennsylvania researchers conducted a series of four studies to assess whether elevated blood alcohol levels raise oxidant stress, and how the stress contributes to liver disease. First, they gave healthy subjects drinks that raised their blood alcohol levels to 0.8, 0.10, and 0.13 g / dL (all within legal limits), and their oxidant stress levels by 69, 289, and 345 % respectively. In two subsequent studies, they administered the same alcoholic beverages to subjects with alcohol-induced liver disease (ALD), and measured their levels of oxidant stress. Researchers found the levels to be 10 times higher in the ALD patients compared to the healthy volunteers, despite the fact that the ALD patients hadn't had a drink for two weeks prior to testing. The extent of oxidant stress was established by measuring the subjects' levels of isoprostanes (iPs), free radical compounds that are excreted through urine.
The good news that came out of the research was that when subjects with liver damage took 2.5 g of vitamin C daily for 10 days, their oxidative levels (iPs) dropped 50 %. This suggests that vitamin C intake may help protect organs against alcohol exposure - although it shouldn't be considered a license to drink more. While light to moderate alcohol intake may reduce the risk of coronary heart disease, previous studies have found that anything over 30 g of alcohol per day is linked to increased mortality due to breast cancer in women and cirrhosis in both sexes, write the study's authors. Moreover, the current research suggests that oxidative stress from excessive alcohol intake over the long term may precede liver damage and contribute to the progression of ALD.
Process discovered to stop shock after blood loss
Shock, caused by blood loss following an injury or high-risk surgery,can precipitate a series of potentially life-threatening events within the body. In a major breakthrough, researchers disrupted the process by blocking release into the intestines of digestive enzymes produced by the pancreas. The NIH-funded study also sheds light on the cellular changes that precede shock.
Scientists at the University of California, San Diego gave one group of rats a drug that inhibited release of pancreatic enzymes and nothing to a second group of rats before surgically triggering shock in the animals. Blood pressure fell, inflammation occurred and multiple organs failed in the untreated control group rats. The treated rats did not develop these or other shock symptoms. "The pancreas produces potent enzymes that can digest any tissue, even our own. These enzymes are regularly released into the intestines to digest our food," said professor Geert Schmid-Schoenbein. "Our theory is that when blood pressure falls sharply in the intestine, pancreatic enzymes in the intestine start to escape from the lumen of the intestine (where they digest food), into the wall of the intestine (where they don't belong). These enzymes produce and release dangerous activators into the blood stream, initiating a cascade of events leading to multiple organ failure."
Researchers are repeating the shock-inducing procedure using different enzyme inhibitors. The study was published in the journal Proceedings of the National Academy of Sciences."We have clearly found a key source of the activators that lead to shock. This is a completely new result," said Schmid-Schoenbein. "With this knowledge, we can begin to explore effective treatments with the possibility of preventing the death of thousands of people each year."
Lasers break up stroke-causing clots
Doctors, for the first time, are using lasers to dissolve blood clots in arteries that supply oxygen and nutrients to the brain, extending the number of hours after a stroke that clot-destroying therapy is possible. Approximately 80 percent of all strokes are caused by clots, but many patients do not seek medical care in time for treatment.
Oregon Stroke Center physicians began testing the devices on a small number of patients and, at an international stroke conference, reported positive preliminary findings. "It looks very promising," said team leader Wayne M. Clark. "But at this point, we're mainly studying the safety. We have achieved complete vessel reopening in some patients, while in others, treatment was not possible due to difficulties getting to the clot with the laser-tipped catheter."
Once doctors confirm a clot has caused the stroke, they must thread the device through the arteries to within one centimeter of the clot. They then activate the laser, which vaporizes the red clot but not the white walls of the surrounding artery. Clark predicts physically removing clots using mechanical means could be the next advance in acute stroke treatment. Currently, doctors can administer a clot-dissolving drug within three hours of the first symptoms. Depending on the location of the clot, lasers can be used eight to 24 hours after the stroke. Mechanical treatments, such as lasers or suction devices, also offer the advantage of speed. They can eliminate the blockage within minutes, versus hours with the drugs.
"We don't know which device or which technique will be the answer, but I think it is reasonable to say that five years from now, mechanical clot disruption will be a major factor in the treatment of acute stroke," Clark added. "Particularly in patients with larger strokes, this type of treatment could be useful."
Zoom lens may help in cancer detection
Colon cancer claims almost 50,000 American lives every year, 10 percent of all cancer deaths. While still the third most common type of cancer, colon malignancies declined a little more than one percent annually during the 1990s. The American Cancer Society attributes the reduction to increased screenings and polyp removal. Benign polyps can gradually become malignant.
Physicians can exam the colon and remove polyps using a lighted tube called a colonoscope. Doctors at the Mayo Clinic are trying a new scope with a magnifying lens that enlarges up to 100 times normal. The new zoom lens lets doctors look for changes in the colon lining's normal honeycomb pattern, which may foretell of polyp formation. The distorted cell clusters are called aberrant crypt foci, or ACF. The doctors count the number of ACFs and take specimens for additional study. The researchers aim to determine if a relationship exists between the frequency of ACFs and development of polyps and colon cancer. "If ACFs are indeed early markers of colon cancer, a technique to identify and sample them would be an invaluable tool for assessing cancer risk and monitoring prevention treatments," says Mayo Clinic gastroenterologist Dr. Christopher Gostout. The magnification colonoscopy study is one of several endoscopic clinical trials under way at Mayo Clinic.
The magnification tool has other uses. In December, researchers in Japan reported success using magnifying colonoscopy in clinical practice to identify cancerous polyps. The doctors found 923 polyps during regular colonoscopy exams, then sprayed a dye and looked at the tissue under the zoom lens. The physicians overall diagnostic accuracy was 88.4 percent. While some polyps considered to be benign during the zoom-lens exam later were found to be malignant, the team concluded that magnifying colonoscopy was useful in deciding when polyps should be removed.
Drugs offer new hope for breast cancer patients
Drugs typically used to treat ovarian and lung cancer have been found to shrink tumors in women with metastatic breast cancer. Mayo Clinic researchers consider the results "encouraging," saying the women experienced one of the highest response rates the medical institution has seen in patients with advanced breast cancer.
Greens and fruit reduce risk of colon cancer
The scientists evaluated the association between dietary carotenoids and different types and states of colon cancer. They collected detailed diet histories from 1,993 patients, ages 30 to 79 years with an initial bout of colon cancer and 2,410 people from the general population who did not have cancer. They found those whose diets contained lutein and zeaxanthin had a lower incidence of the disease. The findings were reported in the February 2000 issue of the American Journal of Clinical Nutrition.
"[These carotenoids] may be involved in regulating cell growth and proliferation, or by preventing damage from free radicals by helping to maintain the integrity of cell membranes," said lead researcher Dr. Martha Slattery. Other dietary carotenoids evaluated did not offer the same cancer protection, because, "Lutein appears to work at a different part of the membrane structure."
Subjects' dietary sources of lutein were spinach, broccoli, lettuce, tomatoes, oranges and orange juice, carrots, celery, greens and eggs. The protective effect was enhanced in younger people. To lower the risk of colon cancer, Slattery suggests people eat more vegetables.
"They are rich sources of lutein as well as folate, another nutrient observed in some studies to reduce risk of colon cancer. Vegetables may also have other unmeasured properties that protect against colon cancer," Slattery continued. "This is only one study; results should be repeated in other studies. Since it is an epidemiologic study, we can only guess how it is actually working. However, inclusion of vegetables in the diet to reduce risk of colon cancer, probably other types of cancer, and other diseases is beneficial."