

 Allergy Drug Claritin Hits Store Shelves Tue Dec 10, 7:16 PM ET
The popular nonsedating antihistamine, available in the same strengths as the prescription version, will cost less over the counter for people without insurance, but more for those with prescription drug coverage.
Ten-milligram tablets are selling for 90 cents to $1.35 each, based on an initial survey of retail outlets, Schering-Plough said. That equates to $27 to $40.50 for a 30-day supply — more expensive than the $5 to $10 copayment for many patients with a prescription plan.
Nonprescription Claritin, the first nonsedating antihistamine on the market without a doctor's prescription in this country, is being sold in three once-a-day formulations, a twice-a-day formulation and a syrup for children as young as two years old.
Schering-Plough initially fought the health insurance industry's push to switch the drug to non-prescription status; Claritin accounts for one-third of the Kenilworth company's roughly $9 billion in annual revenues. Faced with expiration of Claritin's main patent this month and the prospect of both generic and nonprescription competition, Schering-Plough backed down.
The switch could result in prescription plans refusing to cover other prescription-only antihistamines, such as Allegra, Zyrtec and Clarinex, Schering-Plough's successor drug to Claritin, or charging patients much higher copayments for those medicines.
New AIDS Drug
A new type of AIDS drug may be coming to the market a little
sooner than expected. The Food and Drug Administration has
granted a priority six-month review for the experimental drug
Fuzeon, which would be used to treat people with drug-resistant
strains of HIV, The Associated Press reports. The drug belongs
to a new class of drugs called fusion inhibitors, which block HIV
from entering cells. In clinical trials, people with drug-
resistant HIV who added Fuzeon to their drug regimen were twice
as likely to see their virus levels decrease to undetectable
levels than people not taking the new drug, the AP says.
However, the drug is difficult to produce and so would likely be
very expensive, and may cost as much as ,000 to ,000 per
year per patient, the AP says.
How to Break a Blockbuster Drug in Half
The diamond-shaped erection pill costs the same (almost $10 each) whether you get the 25-milligram, 50-milligram or 100-milligram version. This flat-pricing strategy has led many in the over-50 crowd to buy the larger pill and try breaking it up into smaller pieces.
"The patient should be taking a drug based on the dosage recommended by the physician," says Dr. Ira Sharlip, president of the Sexual Medicine Society of North America. "But I can tell you it's common practice for physicians to recommend a dose of 50 milligrams and write a prescription for a 100-milligram tablet."
The ploy could double your fun, but try turned out to be the operative word.
Carmen Reitano, 71, an inventor and Viagra user, was changing in the locker room of his gym not too long ago when the conversation turned to the hazards and difficulties of pill-splitting.
"It explodes," complained one man.
"You can't split it," said another.
"You cut it with a knife and it splits apart with such fury it bounces off the wall, then you have to go find the pieces," said a third.
Reitano had never tried splitting his Viagra pills even though his insurance company only prescribed four a month. After hearing the boys talk, though, he decided to give it a whirl. He went home, took out the kitchen knife and tried to cut open one of his Viagra pills. Nothing happened. He went at it with an X-acto knife blade. Nothing. A hammer. Still, nothing.
Sharlip says his patients have been able to cut their Viagra with store-bought pill-splitters, "and they've worked." However, many others insist the odd-shaped drug doesn't come apart easily.
"The conclusion you come to is that it was purposefully designed to resist splitting," Reitano says. "It's not flat. It's awkward to hold. There's no scoring on the covering." He also discovered that the internal medication is not always bound into a solid block, which is why would-be splitters report that it explodes or breaks apart.
Reitano, who holds several patents, was not to be dissuaded. "It struck me that this pill is made just like wallboard," he says. "It has plaster encapsulated in construction paper. And the way you break that is you score one side and you hit it on the other and it breaks on the fault line."
With this principle in mind, Reitano used standard PVC pipe fitting fixtures to assemble a prototype and took it to the firm that had manufactured one of his other products, an antenna protector for the Motorola StarTAC cell phone. The company built a prototype, tested it, and, lo and behold, it worked.
On Nov. 5, Reitano was awarded patent No. 6,474,525 from the U.S. Patent and Trademark Office for his "pill splitter for complex pill forms." The actual product, the V2 Pill Splitter, is available in two sizes: the 50-milligram pill and the 100-milligram pill.
Now Reitano, who has been married to the same woman for 47 years, is a splitter. And the ranks are growing as men from all over the world purchase the item (for $24.95) directly from Reitano's Web site, www.v2pillsplitter.com. Pfizer, which manufactures Viagra, did not return a call for comment. However, the company recommends against pill-splitting on its Web site.
A Boston urologist told Reitano that more than half of his patients are now splitting pills (after asking the doctor for permission, of course). And a man from New York City called Reitano to tell him that the pill splitter was saving him $1,000 a year. "God bless you," Reitano responded.
What To Do
You can get a primer on erectile dysfunction from the National Institutes of Health. And the U.S. Food and Drug Administration (news - web sites) has more on Viagra
New Drug Tops Gold Standard in Breast Cancer Trial
Thu Mar 21, 1:13 PM ET
By Patricia Reaney
BARCELONA, Spain (Reuters) - A new breast cancer (news - web sites) drug is better than the best currently available treatment in preventing postmenopausal women with early disease from developing a new tumor in the other breast, researchers said Thursday.
The drug, called anastrozole, is produced by AstraZeneca PLC under the brand name Arimidex.
In research presented at the 3rd European Breast Cancer Conference, scientists said the drug outperformed tamoxifen, currently the gold standard for treatment, in a trial of women with early breast cancer.
Women who were given anastrozole for two and a half years had a 58% lower risk of developing a new tumor in the other breast than those taking tamoxifen, which is also made by AstraZeneca.
"It is an important finding. The reduction in the development of contralateral (other) breast cancer was very much greater than we had anticipated," Dr. Jeffrey Tobias of University College Hospital London, one of the researchers on the study, told Reuters.
Tamoxifen cuts the risk of a new cancer in the other breast by 50% and anastrozole slashes it in half again.
The study, one of the largest breast cancer trials ever conducted, involved more than 9,000 women who were given either anastrozole, tamoxifen or a combination of both. The combination therapy was no better than tamoxifen alone.
Anastrozole works by inhibiting production of the female hormone estrogen in postmenopausal women. Estrogen is linked to the development of cancer, and most cases of breast cancer are in postmenopausal women.
But the drug does not work in younger women and it may increase the risk of fractures or osteoporosis.
Tobias said women given anastrozole had fewer side effects such as blood clots, hot flushes and cancer of the uterus than the tamoxifen group.
 new teste for celiac disease Lancet 2002; 359: 945-46.
The clinicians said the immunochromatographic assay detects antibodies to transglutaminase quickly and easily. It is highly accurate in detection of untreated patients with coeliac disease, and detects both IgA and IgG antibodies to transglutaminase, and which can prevent the misdiagnosis of patients with a deficit of IgA, a frequent trait of coeliac disease.
 Journal of the National Cancer Institute, Vol. 94, No. 5, 391-398, March 6, 2002
© 2002 Oxford University Press
Prospective Study of Tomato Products, Lycopene, and Prostate Cancer Risk
Edward Giovannucci, Eric B. Rimm, Yan Liu, Meir J. Stampfer, Walter C. Willett
Affiliations of authors: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston.
Correspondence to: Edward Giovannucci, M.D., Sc.D., Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA (e-mail: edward.giovannucci@channing.harvard.edu).
Background: Some data, including our findings from the Health Professionals Follow-Up Study (HPFS) from 1986 through January 31, 1992, suggest that frequent intake of tomato products or lycopene, a carotenoid from tomatoes, is associated with reduced risk of prostate cancer. Overall, however, the data are inconclusive. We evaluated additional data from the HPFS to determine if the association would persist. Methods: We ascertained prostate cancer cases from 1986 through January 31, 1998, among 47 365 HPFS participants who completed dietary questionnaires in 1986, 1990, and 1994. We used pooled logistic regression to compute multivariate relative risks (RR) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: From 1986 through January 31, 1998, 2481 men in the study developed prostate cancer. Results for the period from 1992 through 1998 confirmed our previous findings—that frequent tomato or lycopene intake was associated with a reduced risk of prostate cancer. Similarly, for the entire period of 1986 through 1998, using the cumulative average of the three dietary questionnaires, lycopene intake was associated with reduced risk of prostate cancer (RR for high versus low quintiles = 0.84; 95% CI = 0.73 to 0.96; Ptrend = .003); intake of tomato sauce, the primary source of bioavailable lycopene, was associated with an even greater reduction in prostate cancer risk (RR for 2+ servings/week versus <1 serving/month = 0.77; 95% CI = 0.66 to 0.90; Ptrend<.001), especially for extraprostatic cancers (RR = 0.65; 95% CI = 0.42 to 0.99). These associations persisted in analyses controlling for fruit and vegetable consumption and for olive oil use (a marker for Mediterranean diet) and were observed separately in men of Southern European or other Caucasian ancestry. Conclusion: Frequent consumption of tomato products is associated with a lower risk of prostate cancer. The magnitude of the association was moderate enough that it could be missed in a small study or one with substantial errors in measurement or based on a single dietary assessment.
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New Acne Drug Has Fewer Adverse Effects
By Jennifer Warner
CHICAGO (MedscapeWire) Dec 18 - A powerful new drug for acne may work without adverse effects, according to Canadian researchers. They presented their data at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy on Sunday.
More than 85% of adolescents suffer from some form of acne, and nearly one-fifth of all visits to dermatologists are prompted by the need for effective acne treatment. Although antibiotics have been used for more than 30 years to treat acne, the bacterium responsible the most common form of acne is growing increasingly resistant to standard treatments.
Newer prescription treatments, such retinoids that are derived from vitamin A, can provide relief for some sufferers, but the drugs also carry the risk of potentially severe effects such as birth defects and psychological disorders.
The new drug, currently known as MBI 594AN, appears to attack acne-causing bacteria so quickly that they don't have a chance to become resistant.
"This product seems to kill very rapidly - it attacks the cell walls and reduces lesions quite quickly," says Jenny Robinson, MD, manager of medical affairs at Micrologix Biotech, the Vancouver-based company that developed the drug.
Robinson says the preliminary tests also show that MBI 594AN, which is a topical alcohol-based solution, also has the potential to reduce the inflammation associated with acne lesions.
Because the naturally derived active ingredient isn't absorbed into the bloodstream, researchers say it reduces the likelihood of adverse effects seen in other acne medications.
The drug is currently in phase II clinical testing and has not yet been approved for use by the US Food and Drug Administration. Researchers say they hope to have the drug on the market within the next few years.
Jennifer Warner is a medical writer with Medscape Health, Medscape's sister site for patients.
MedscapeWire is edited by Deborah Flapan, an associate editor at Medscape. Send press releases and comments to medscapewire2@medscapeinc.com.
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New York Scores Well on U.S. Air-Pollution Report Card
WASHINGTON (Reuters) - New York won the highest ranking and Oklahoma City the lowest among the 50 largest US cities for spending on mass transit and reducing smog from cars and trucks, according to a Sierra Club (news - web sites) air pollution report card issued on Tuesday.
Although cars today produce much less air pollution than a generation ago, people are driving more. The average American driver spends about 443 hours per year--the equivalent of 55 eight-hour workdays--behind the wheel, the green group said.
New York won the highest grade in the Sierra Club report, an A, for its spending on public transit.
The city is the only one in the nation that spent more money on transportation alternatives than on new roads. New York spent $460.69 per person on mass transit and $360.97 per person on highways.
At the same time, New York emitted the least amount of smog per person from cars and trucks, about 54 pounds annually, according to the green group.
On the other end of the spectrum, Oklahoma City flunked the Sierra Club analysis. The city had a high amount of smog from cars and trucks, 137 pounds per person per year, and spent just $15.31 per person on public transit and $262.96 per person for highway construction.
 During the study, patients were continuously infused with Genasense for five days and then treated with a standard regimen of the anticancer-drugs fludarabine, cytarabine, and filgrastim.
Of the 20 patients, nine showed signs that all leukemia cells in the blood and bone marrow had disappeared, indicating that these patients had gone into complete remission.The researchers also point out that the side effects associated with chemotherapy, including fever, nausea, and vomiting, did not occur at higher-than-expected levels, suggesting that that the Genasense did not increase the toxicity of the chemotherapy.
"This is a very encouraging first step, which suggests that Genasense may have a role in making leukemia patients sensitive to chemotherapy again," Marcucci noted in a written statement.
"Genasense would probably be effective in treating several different types of cancer, but only those that express Bcl-2," Marcucci told Reuters Health.
According to Marcucci, some other cancers that may be helped by this drug include Hodgkin's lymphoma and melanoma. "In general, I would say that this drug would be useful for every type of cancer that would overexpress Bcl-2," he said.
 From
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MedscapeWire
New Sepsis Treatment Cuts Death Risk Almost 20%
May 23, 2001
By Deborah Flapan
New York - A new treatment for severe sepsis reduces the relative risk of death by almost 20%, according to a study presented Tuesday at the American Thoracic Society's 97th International Conference in San Francisco, California.
The treatment, recombinant human activated protein C (rhAPC), has the potential to have a major impact on mortality rates for severe sepsis, said lead study author Gordon Bernard, MD, Professor of Medicine at Vanderbilt University in Nashville, Tennessee. "There are up to 750,000 sepsis cases in the United States each year, and the death rate is in the 30%-35% range," said Dr. Bernard, who is also Associate Director of the Division of Allergy, Pulmonary and Critical Care Medicine.
Sepsis is a serious infection caused by bacteria or other microorganisms that have entered a wound or body tissue. Tissue damage and a dramatic drop in blood pressure result from the presence of these organisms, their toxins or other products in the blood. People with diseases such as diabetes and cancer that compromise the immune system are at higher risk of developing sepsis. Sepsis sometimes develops as a complication of pneumonia or meningitis, or as a result of perforated appendix or ulcer, or of any trauma that damages a body cavity. When sepsis develops, the body tries to "wall off" the infection to keep it from spreading. One way it does this is by coagulating blood in small vessels, in an attempt to prevent the infection from draining to the rest of the body. "But severe sepsis involves the entire body, and the immune system can't wall it off," Dr. Bernard said. "Instead, this coagulopathy occurs throughout the body and ends up damaging tissues and organs, sometimes with deadly results."
In trying to counteract the clotting, the body uses a substance called Protein C, but levels of this protein are depleted very quickly. The new treatment is a human recombinant version of the protein, which limits and reverses the coagulopathy and thus counteracts damage to tissue and organs, and improves survival, Dr. Bernard said.
The phase III multicenter, international study included 850 severe sepsis patients who received rhAPC and 840 patients who received a placebo. Treatment was administered intravenously for 96 hours. Twenty-eight days later, 24.6% of patients receiving rhAPC had died, compared with 31.4% in the control group.
"We conducted a battery of tests to measure the blood's coagulation status and found substantial abnormalities before the treatment, and we saw a restoration of more normal values after treatment," Dr. Bernard said.
Eli Lilly and Company, which manufactures rhAPC, submitted a New Drug Application under the brand name Zovant to the US Food and Drug Administration in January 2001.
MedscapeWire is edited by Deborah Flapan, an associate editor at Medscape. Send press releases and comments to medscapewire2@medscapeinc.com
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NOTE: To view the article with Web enhancements, go to:
Expert Column
Pediatric ID Update: An Itch in Time... Practical Treatment of Tinea Capitis
Robert W. Steele, MD
[Medscape Infectious Disease, 2001. © 2001 Medscape, Inc.]
Introduction
Tinea capitis, or ringworm of the scalp, is a common condition diagnosed frequently in the primary care physician's office. This infection, while not a particularly deadly illness, can often inspire fear and dread in many parents whose children have acquired it. There is myth and mystery surrounding this condition, and parents may consider its acquisition to reflect on their hygiene techniques. Aside from learning the causes and treatment of tinea capitis, it is important for the primary care physician to recognize the true epidemiology in order to give parents accurate anticipatory guidance to avoid the "dreaded" ringworm.
The etymology of the word ringworm reveals that the term came into use in the 15th century and was used to describe any skin rash that was patterned in a ring formation.[1] However, it wasn't until the mid-1800s that formal microscopic examination revealed that the true etiology of hair loss was from dermatophyte invasion. Several species of fungus were identified at the end of the 19th century as causing tinea capitis, and straightforward culture methods were developed to aid in their isolation.[2]
There are now more than 40 species of fungi recognized to commonly invade the skin and/or hair. Six of these represent the most common causes of tinea capitis (Table 1). These fungi may be found in soil, on humans, or on pets commonly found in the home, and the relative frequency of a species is often determined simply by geography. Trichophyton tonsurans has now supplanted Microsporum canis as the most common dermatophyte to cause tinea capitis in the United States.[3] This is contrasted with Europe, where M canis continues to play a major role in infection.
While tinea capitis can affect all children, poorer children and those residing in crowded living conditions may be more at risk for infection. Hair care practices, including hairstyle, frequency of washing, and the use or nonuse of hair conditioner, oils, or grease, do not appear to play a significant role in acquiring tinea capitis.[4] When cases arise in a household, there is a high prevalence of an asymptomatic carrier within the home.[5] It is common for tinea capitis to be spread through combs, hairbrushes, and fallen infected hairs. And since untreated asymptomatic carriers may continue their carrier status even 2 months later, it has been recommended that all members of the household be treated simply to eliminate any carriers within the family.[6]
Tinea capitis may appear clinically in several typical scenarios. The hair may simply show some thinning with a scaly appearance to the scalp. The hair may be almost absent due to hair breakage, giving the scalp a "dotted" appearance where the hair stump remains in the scalp. This often gives a distinct border of hair loss. There may not only be hair loss but significant inflammation producing pustules, keratin accumulation, and kerion formation. Each of these clinical entities may be associated with occipital or cervical lymphadenopathy.
Treatment Options
Tinea capitis is caused by invasion of the hair by dermatophytes. Because there is direct invasion, topical therapy is usually inadequate, simply because it is not possible to effectively get the medication to the site of infection. Therefore, oral therapy is the mainstay of successful eradication. Since its initial use in the 1950s, griseofulvin has remained the treatment of choice for tinea capitis.[7] However, there are now several therapeutic options available. Understanding their pros and cons allow for the appropriate selection to be made (Table 2).
Griseofulvin is a medication derived from Penicillium, which produces its antifungal effect by inhibiting the assembly of microtubules. The drug establishes a high level within the stratum corneum. Then, as the keratin is exfoliated, it is replaced by uninfected tissue.[8] It has a notoriously erratic absorption that is dependent on concurrent dietary fat intake. It is a safe medication with infrequent side effects, which usually subside as the therapeutic course continues.
Itraconazole is a relatively new antifungal medication. It, too, has improved absorption when taken with increased dietary fat. Its concentration in the skin is much higher than that of the plasma because of its high lipophilic properties. In fact, significantly high concentrations remain in the skin even 4 weeks after the medication has been discontinued. This has led to successful use of this medication in children using pulsed dosing of 1 week duration in 2-week intervals.[9] Fluconazole, like itraconazole, is a triazole compound but is quite water soluble. This gives it the advantage of reliable and excellent gastrointestinal absorption regardless of dietary fat intake. However, its dosage must be adjusted in those with renal insufficiency.
Terbinafine is an allylamine antifungal drug that can attain concentrations in the corneum stratum 75 times that of the plasma. Studies in children have shown equivalent effectiveness in eradicating infection when compared with griseofulvin.[11-12]
Clinical experience with each of these newer medications is small. However, with the possibility of shorter duration of treatment, their increased unit cost may be less significant than the decreased cost of total therapy.
The Other Treatment: Information
Finally, it is important for healthcare professionals to give parents reliable information concerning the transmission of tinea capitis, particularly when the infection has been identified in a child in the classroom. The Committee on Infectious Diseases of the American Academy of Pediatrics has stated that children receiving treatment for tinea capitis may attend school. Haircuts, shaving of the head, or wearing a cap during treatment are not necessary.[13] This recommendation is made for a couple of reasons. Asymptomatic carriers within the home most likely play the greatest role in transmission. Thus, as long as fomites such as combs and brushes are not shared, school contact is much less likely to spread infection than infection in the home. Second, it is impractical to keep children out of school for the 4-8 weeks it takes to completely eradicate the infection.[14] It is hoped that more-rapid diagnostic assays will be developed in the future that will aid in identifying those carriers so that more effective treatment strategies can be employed when outbreaks occur.
Table 1. The Most Common Species Responsible for Tinea Capitis
Microsporum canis
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Microsporum gypseum
|
Trichophyton tonsurans
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Trichophyton mentagrophytes
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Trichophyton violaceum
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Trichophyton verrucosum
|
Table 2. Antifungal Medications for Tinea Capitis
Drug
|
Recommended
Dosages
|
Recommended
Duration of
Treatment
|
Monitor Liver
Enzymes?
|
Liquid
Suspension?
|
Griseofulvin
|
20 mg/kg/day
|
6-8 weeks
|
No
|
Yes
|
Itraconazole
|
5 mg/kg/day
|
4-6 weeks
|
Yes
|
No
|
Ketoconazole
|
Not for pediatric use yet
|
N/A
|
N/A
|
No
|
Fluconazole
|
6 mg/kg/day
|
3 weeks
|
No
|
Yes
|
Terbinafine
|
10-20 kg = 62.5 mg/day
20-40 kg = 125 mg/day
> 40 kg = 250 mg/day
|
2-4 weeks
|
Yes, if treatment > 4 weeks
|
No
|
From
Medscape News
MedscapeWire
Walnuts May Decrease Risk of CVD
July 3, 2001
By Hong Mautz
New York - A new study shows that walnuts can lower low-density lipoprotein (LDL) cholesterol levels and reduce cardiovascular disease (CVD) risk.
Earlier research has suggested that nuts in general provide health benefits, specifically coronary benefits. Some studies have shown that eating 5 servings of nuts per week reduced the risk of heart attacks by 40%-50%. Although there are several theories on the potential mechanisms of the protective effect of nuts, the exact mechanism is unknown.
In this study, published in the July issue of the American Journal of Clinical Nutrition, researchers looked at walnuts exclusively and found that adding walnuts to both regular and low-fat diets significantly reduced total cholesterol as well as the low-density lipoprotein (LDL) cholesterol levels. This finding, researchers say, suggests that the way walnuts lower cholesterol is by changing lipid distribution in favorable ways.
"What's different about walnuts is that they are rich in polyunsaturated fat, while other nuts are rich in monounsaturated fat," says study author Sidika Kasim-Karakas, MD, of the department of endocrinology and nutrition at the University of California at Davis. "We have identified a potential additional mechanism by which walnuts prevent heart disease."
Five men and 13 postmenopausal women (average age, 60 years) who have high cholesterol and high triglyceride levels) participated in the study. They were given 4 diets in sequence over a period of 5.5 months:
Regular (pre-study) diet.
Regular diet + walnuts.
Low-fat diet.
Low-fat diet + walnuts.
Participants were on each diet for 6 weeks. At the end of each diet, researchers measured cholesterol and triglyceride levels. "Wherever we added walnuts, regardless of [whether it was] the second or the fourth phase, we had favorable changes in the small [density] LDL," says Dr. Kasim-Karakas.
"We showed a decrease in small-density LDL from 46% in the regular diet to 33% in the regular plus walnuts diet," says Dr. Kasim-Karakas. More studies on walnuts or nuts in general are needed to understand better the mechanisms of their protective effect, he said.
John Sabaté, MD, DrPH, professor of nutrition at the School of Public Health at Loma Linda University, California, who has done extensive research on walnuts, says that his studies have shown that eating walnuts lowered cholesterol among both healthy men and women as well as people with high cholesterol.
"This study confirms our previous results that walnuts reduce lipoprotein cholesterol levels," says Sabaté. "Supplementation of walnuts lower[s] not only the total amount of cholesterol, but the LDL cholesterol, preferentially lower[ing] the small particle LDL."
But Dr. Sabaté points out that it is difficult to distinguish the precise effects of different diets because they were administered consecutively. "The results need to be repeated, especially on the small LDL," says Sabaté.
One interesting point in the study is that walnuts did not increase weight in people who consumed walnuts in addition to their regular diets, says Lola O'Rourke, MS, RD, a spokesperson for the American Diatetic Association.
"Although the mechanism is not entirely clear, one theory is that nuts are very satiating, they give a sense of satisfaction so people stop eating sooner," Ms. O'Rourke explains.
O'Rourke points out that over the last few years, fat intake has gone down, yet the number of Americans who are overweight has gone up. One reason may be that there are many low-fat and non-fat products popping up on the market, and people are probably eating more of them.
"Many people in our society are 'fat phobic,' and nuts are often perceived as something that should be avoided for that reason," says O'Rourke. "It's important to keep in mind that some fat is still a good thing. The basis of a balanced diet is variety and moderation. Nuts fit into that extremely well."
Am J Clin Nutr. 2001;73(7):000-000
Hong Mautz is senior news writer with CBS Healthwatch, Medscape's sister site for patients.
MedscapeWire is edited by Deborah Flapan, an associate editor at Medscape. Send press releases and comments to medscapewire2@medscapeinc.com.
Two Controlled Trials of Antibiotic Treatment in Patients with Persistent Symptoms and a History of Lyme Disease
Mark S. Klempner, M.D., Linden T. Hu, M.D., Janine Evans, M.D., Christopher H. Schmid, Ph.D., Gary M. Johnson, Richard P. Trevino, B.S., DeLona Norton, M.P.H., Lois Levy, M.S.W., Diane Wall, R.N., John McCall, Mark Kosinski, M.A., and Arthur Weinstein, M.D.
ABSTRACT
Background It is controversial whether prolonged antibiotic treatment is effective for patients in whom symptoms persist after the recommended antibiotic treatment for acute Lyme disease.
Methods We conducted two randomized trials: one in 78 patients who were seropositive for IgG antibodies to Borrelia burgdorferi at the time of enrollment and the other in 51 patients who were seronegative. The patients received either intravenous ceftriaxone, 2 g daily for 30 days, followed by oral doxycycline, 200 mg daily for 60 days, or matching intravenous and oral placebos. Each patient had well-documented, previously treated Lyme disease but had persistent musculoskeletal pain, neurocognitive symptoms, or dysesthesia, often associated with fatigue. The primary outcome measures were improvement on the physical- and mental-health–component summary scales of the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) — a scale measuring the health-related quality of life — on day 180 of the study.
Results After a planned interim analysis, the data and safety monitoring board recommended that the studies be discontinued because data from the first 107 patients indicated that it was highly unlikely that a significant difference in treatment efficacy between the groups would be observed with the planned full enrollment of 260 patients. Base-line assessments documented severe impairment in the patients' health-related quality of life. In intention-to-treat analyses, there were no significant differences in the outcomes with prolonged antibiotic treatment as compared with placebo. Among the seropositive patients who were treated with antibiotics, there was improvement in the score on the physical-component summary scale of the SF-36, the mental-component summary scale, or both in 37 percent, no change in 29 percent, and worsening in 34 percent; among seropositive patients receiving placebo, there was improvement in 40 percent, no change in 26 percent, and worsening in 34 percent (P=0.96 for the comparison between treatment groups). The results were similar for the seronegative patients.
Conclusions There is considerable impairment of health-related quality of life among patients with persistent symptoms despite previous antibiotic treatment for acute Lyme disease. However, in these two trials, treatment with intravenous and oral antibiotics for 90 days did not improve symptoms more than placebo.
Germ Warfare For Tumors
A virus harmless to healthy cells may be a deadly weapon against
cancerous ones. In a study published in the Journal of the
National Cancer Institute, researchers used reovirus, a bug
commonly found in human lungs and digestive systems, to shrink
brain tumors in mice. The researchers say a clinical trial using
reovirus to fight cancer in humans could be underway in about six
months, The Associated Press reports. In the study, researchers
implanted an aggressive form of brain cancer called glioblastoma
into 24 mice. Half the mice were then given live reovirus
injections and the other half were given injections of dead
reovirus. The mice who got dead reovirus injections quickly dies
from their cancer, but eight of the 12 mice who got live reovirus
injections were still alive 90 days later. Those mice even
gained weight and appeared healthy, the AP reports. The
researchers say that normal healthy cells are able to block
infection from reovirus, which is why it normally does not cause
illness. But cancer cells are susceptible to infection, and so
can be killed by reovirus, they say. The lead researcher owns
stock in the company that may conduct the human trials of the
reovirus therapy, the AP says.
For more on cancer, go to: http://www.intelihealth.com/IH/ihtIH/EMIHC000/8096/8096.html
Blood Pressure Drugs Fend Off Stroke
A combination of blood pressure medication and diuretics could be
a lifesaver for stroke patients. A study presented at the
European Society of Hypertension meeting in Milan finds that this
drug combination may halve a patient's risk of having a second
stroke, The Associated Press reports. In the study, 6,100 stroke
patients worldwide were given a combination of the ACE inhibitor
Aceon and the diuretic Lozol or else dummy pills for a period of
four years. The results: 150 of the patients taking the drug
combination had a stroke, compared to 255 of the patients taking
the placebo. The drug combination lowered risk even in patients
who'd had normal blood pressure, the AP says. The patients
taking Aceon and Lozol also had lower risk of complications such
as heart attack or dementia, the AP says. The question that
remains is whether it is the lower blood pressure or some other
effect of the drugs that provides the benefit. The study was
partly funded by the French pharmaceutical company Servier, which
manufactures Aceon.
For more on stroke, go to: http://www.intelihealth.com/IH/ihtIH/EMIHC000/8772/8772.html
This Doctor's Guide DGReview has been recommended by Dr. Bruce Roseman
Title: Early Antibiotics Prevent Lyme Disease After Deer Tick Bite
A DGReview of : Prophylaxis with Single-Dose Doxycycline for the Prevention of Lyme Disease after an Ixodes scapularis Tick Bite
New England Journal of Medicine (NEJM)
Casodex (Bicalutamide) Significantly Reduces Risk of Prostate Cancer Progression
TORONTO, ON -- June 20, 2001 -- A once daily dose that slows disease progression offers new hope for hundreds of thousands of men around the world diagnosed with prostate cancer each year.
The first results of the largest ever trial in prostate cancer, the Early Prostate Cancer (EPC) Programme, showed that, in comparison with standard care alone (surgery, radiotherapy or watchful waiting), bicalutamide 150mg (Casodex™) reduces the risk of the cancer progressing by 42 per cent and reduces the risk of the cancer spreading to the bones by approximately 33 percent. In addition, in patients taking bicalutamide 150mg there was a significant delay in prostate-specific antigen (PSA) rise - a second indicator that the disease is under better control.
As with most cancers, prostate cancer patients have a better chance of survival if diagnosed early. Current standard treatment for early prostate cancer (i.e. surgery, radiotherapy or watchful waiting) is not always successful, as there is often disease recurrence or progression. The growth of prostate cancer is known to be stimulated by the male (androgenic) hormone, testosterone, and therefore the early use of an anti-androgen, in addition to standard treatment, could improve the outlook for men with prostate cancer. A similar approach has proved very successful in the treatment of breast cancer, where the use of tamoxifen (Nolvadex®, an anti-estrogen), in addition to standard treatment, has been shown to improve the survival of women with early disease.
"Progression of prostate cancer is associated with a number of serious complications such as anaemia, urinary obstruction, kidney failure, severe pain and pathological fractures caused by bone metastases. I believe that these first promising results from the EPC Programme will offer real hope for prostate cancer patients as we are already able to show a significant reduction in the risk of disease progression," said Dr. Yves Fradet, Professor of Surgery/Urology and Chairman of the Department of Surgery at Laval University in Quebec, and a Principal Investigator in the EPC Programme. "These results, although requiring further follow-up to assess their impact on patients' survival, already provide hope to the patients."
"The EPC Programme results are very exciting and will undoubtedly trigger discussion around the role of adjuvant hormonal therapy in the treatment of early prostate cancer. Inevitably, there will be some reservation regarding the preliminary nature of the data, which does not yet include any information on survival," said Dr. Jack Barkin, Chief of Urology at Humber River Regional
Hospital in Toronto, Ontario. "Nonetheless, prolonging the time to clinical progression will result in significant benefits for patients with early prostate cancer, especially those at high risk of experiencing the morbidity associated with disease progression."
The data will be presented on June 27th, 2001 at the Canadian Urology Association (CUA) meeting in Toronto, Ontario. The data have already been submitted to the United Kingdom regulatory authorities and will be submitted to other regulatory authorities around the world during the course of 2001. The aim of such submissions is to provide clinicians and patients with an additional treatment option for localized and locally advanced prostate cancer.
The majority of side effects reported were predicted from the mode of action of the drug. Breast swelling and breast pain were the most frequent, but in the majority of patients, these were mild to moderate, frequently resolving or improving when therapy was withdrawn.
The EPC Programme involved a total of 8,113 men with localized and locally advanced prostate cancer and was carried out in Europe, North America, Scandinavia, South Africa, Australia, Israel and Mexico.(1) In Canada, 14 centers participated in the study and 318 patients were involved. Patients were randomized to receive bicalutamide 150mg once daily or placebo, in addition to standard care.
Despite an increase in public awareness and screening, prostate cancer does not have the same level of public recognition as other forms of cancer, such as breast cancer. Yet, it is the second most commonly diagnosed male cancer in Canada, as well as many western countries, after lung cancer. According to the National Cancer Institute of Canada, it is estimated that nearly 17,800 new cases of prostate cancer will be diagnosed and 4,300 men will die from the disease in Canada during 2001.(2)
References:
1. WA See, D McLeod, P Iversen, M Wirth. The Bicalutamide Early Prostate Cancer Program. Demography. Urol Onc 2001;vol6: 43-47.
2. National Cancer Institute of Canada, Canadian Cancer Statistics 2001, Toronto, Canada
SOURCE: AstraZeneca Canada
Early Antibiotics Prevent Lyme Disease After Deer Tick Bite
New England Journal of Medicine (NEJM) 06/13/2001 By Anne MacLennan
A single 200-mg dose of doxycycline within 72 hours after a deer tick bite can prevent development of Lyme disease.
This is the controversial finding of a multicentre study in an area of the United States where the incidence of Lyme disease is among the highest in the world.
Study results have been published online by the New England Journal of Medicine in advance of the formal publication date and because of their potential important in treatment.
However, findings also confirm that even in the study area, Westchester County, New York, where the disease is hyperendemic, risk of Lyme disease after a deer tick bite is low at 3.2 percent overall among recipients.
This study also confirms experimental evidence that ticks must become at least partially engorged with blood, i.e. they must feed for many hours, before Borrelia burgdorferi is transmitted.
The report comes on the heels of a recent recommendation from the Infectious Diseases Society of America that people bitten by deer ticks (Ixodes scapularis) should not routinely receive antimicrobial chemoprophylaxis.
This recommendation was based on risk and consequences of Lyme disease, as well as costs, adverse effects and efficacy of antimicrobial Prophylaxis.
Participants in this double-blind, placebo-controlled trial of treatment with a single 200-mg dose of doxycycline were 482 people who had removed attached I. scapularis ticks from their bodies within the previous 72 hours.
At baseline, and at three weeks and six weeks, researchers interviewed and examined the patients and did serum antibody tests as well as blood cultures for Borrelia burgdorferi.
Entomologists confirmed the species of the ticks and classified them according to sex, stage and degree of engorgement - a sophisticated assessment not normally available in clinical practice.
Erythema migrans developed at the tick bite site in a significantly smaller proportion of subjects on doxycycline than on placebo.
None of the patients developed objective extracutaneous signs of Lyme disease, and there were no asymptomatic seroconversions.
Treatment with doxycycline was linked with more frequent adverse effects (in 30.1 percent of those on doxycycline versus 11.1 percent of those on placebo). These effects were primarily nausea and vomiting.
Erythema migrans was also found to develop more frequently after untreated bites from nymphal ticks than after bites from adult female ticks and, particularly, after bites from nymphal ticks that were at least partially engorged with blood.
Who should receive doxycycline for tick bite? The treatment may be reasonable for people bitten by ticks in areas where incidence of the disease is high and the tick is a nymphal deer tick at least partially engorged with blood.
However, in the far more common circumstances in which the bite occurs in an area where the disease incidence is low, in which the tick is not a nymphal deer tick or is not at least partially engorged, risk of disease is likely to be so low that this treatment is not indicated.
In 1999, 92 percent of all reported cases of the disease in the US occurred in just nine states. However, in most areas of the country, and indeed even in many areas of these nine states, risk of Lyme disease is very low.
Indeed, most tick bites in the United States are from species that do not transmit Lyme disease.
In Europe and Asia, both the species of bacteria that cause Lyme disease and the ticks that are vectors are different from those in the US.
Source:
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NIH/National Institute Of Allergy And Infectious Diseases (http://www.niaid.nih.gov/)
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NIAID Collaboration Yields New Test For Lyme Disease
A new test developed with funding from the National Institute of Allergy and Infectious Diseases (NIAID) has been shown to be highly accurate and sensitive for detecting antibodies to Lyme disease. Produced by Immunetics, Inc. of Cambridge, Massachusetts, the new assay recently won approval from the Food and Drug Administration (FDA) for use as a diagnostic test for Lyme disease.
It is the first diagnostic tool to use a synthetic product called C6, a hybrid chemical marker based on components derived from the surface of Borrelia burgdorferi, the tick-borne bacterium that causes Lyme disease. The C6 test is sensitive only to antibodies generated during an active infection.
Lyme disease can be difficult to diagnose, especially in later stages of infection when an individual’s antibodies can fall to very low levels. Laboratory testing showed the C6 approach resulted in a high rate of sensitivity to antibodies from both the early and late stages of Lyme disease. The kit also resulted in fewer false positive readings when compared with current screening methods. Significantly, no false positive readings were obtained when the kit was used to test people who had previously received Lymerix®, the Lyme disease vaccine. Another advantage is the test’s ability to detect antibodies specific to both U.S. and European strains of Borrelia.
“The C6 test is the result of years of collaboration in an ongoing effort to improve our ability to diagnose Lyme disease,” explains microbiologist Phillip Baker, Ph.D., NIAID’s Lyme disease program officer. “This new approach is an important first step in that direction.”
NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
The National Institute of Allergy and Infectious Diseases is a component of the National Institutes of Health, U.S. Department of Health and Human Services
 Title: Fruit, Vegetables Do Matter Against Heart Disease, Says Large, Long-Term Study
URL: http://www.annals.org/issues/v134n12/abs/200106190-00010.html
Ann Intern Med. 2001;134: 1106-1114. "The Effect of Fruit and Vegetable Intake on Risk for Coronary Heart Disease"
06/21/2001 08:03:46 AM
By Anne MacLennan
A large study has tied consumption of fruits and vegetables, particularly those rich in vitamin C and green leafy vegetables, to a protective effect against coronary heart disease.
Until now, data on the relationship have been sparse, although many constituents of fruits and vegetables are known to reduce risk for coronary heart disease.
This was a prospective cohort study set within the large Nurses' Health Study and Health Professionals' Follow-up Study in the United States.
Kaumudi J Joshipura and colleagues from Harvard School of Public Health, Harvard School of Dental Medicine, Channing Laboratory, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts did the research.
Participants were 84,251 women aged 34 years to 59 years who were followed for 14 years and 42,148 men aged 40 years to 75 years who were followed for eight years.
All of the participants were free of diagnosed cardiovascular disease, cancer and diabetes at baseline.
As the main outcome measure, researchers used incidence of nonfatal myocardial infarction or fatal coronary heart disease (1,127 cases in women and 1,063 in men).
Diet was assessed by food-frequency questionnaires.
Once researchers took standard cardiovascular risk factors into account, people in the highest quintile of fruit and vegetable consumption had a relative risk for coronary heart disease of 0.80 versus those in the lowest quintile.
Indeed, each one-serving/day increase in fruit or vegetable intake was linked with a four percent lower risk for coronary heart disease.
Green leafy vegetables and vitamin C-rich fruits and vegetables contributed most significantly to the apparent protective effect of total fruit and vegetable intake.
http://www.annals.org/issues/v134n12/abs/200106190-00010.html
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Diet Linked to One in Three Cancers(from Yahoo New)
By Ray Dunne
LONDON (Reuters Health) - Almost one in three cancers could be prevented through healthier eating, a major international conference heard this week.
Researchers making presentations at the European Conference on Nutrition and Cancer in Lyon, France, linked thousands of cases of cancer in the western world to poor diet and a lack of exercise.
Conference attendees were also told of the preliminary findings of one of the world's largest studies investigating the relationship between the disease and what people eat.
The European Prospective Investigation into Cancer and Nutrition (EPIC)--one of the biggest in terms of individual data--has confirmed many previous studies showing that some food can increase the risks of cancer while others can have a protective effect on the human body.
However, it has also provided some new ideas and raised doubts about previously long-held theories.
The study, which is looking at the diets of more than 500,000 people from nine European countries, has confirmed once again that eating fruit and vegetables can ward off the disease, in particular colon and rectal cancer.
However, it casts doubts on the protective effects of fruit and vegetables on other cancers. For instance, the study found no evidence to suggest they can ward off cancers of the stomach and lungs.
``We do confirm that the consumption of fruit and vegetables reduces the risk of colorectal cancer and cancers of the mouth, pharynx and oesophagus,'' Dr. Elio Riboli, one of the organisers of the conference and one of those heading up the study, told Reuters Health.
``But we were surprised not to find at this early stage a clear protection for cancer of the stomach and lungs...for the time being the protection for lung and stomach cancer is a little weaker than we expected,'' he added.
The preliminary results have also raised questions about the long-held belief that eating red meat can increase the risk of cancer.
``For years there has been a fear that red meat, particularly beef, lamb and pork, could increase the risk of colorectal cancer,'' said Riboli. ``We have been looking very closely at this issue and the results don't support that. We cannot exclude a 10% to 15% increase for heavy consumption of meat, but the risk is not as we may have thought maybe 10 years ago.''
Riboli said the study would now examine the effects of different meats. ``This is interesting because it is the first time a large study has made a clear separation between processed and fresh meat. Previously, we were only concerned with total meat consumption.''
He added, ``We are now looking into the different types of meat and why processed meat may be a greater risk than fresh meat and to see what is in processed meat that may increase the risks.''
The study also highlights the long-established risks of alcohol and tobacco. Its latest findings suggest that smoking more than a pack of cigarettes each day can increase the risk of cancer by eight times.
Similarly, drinking a bottle of wine every day can boost the chances of getting the disease by nine times.
But the study found that excessive smoking and drinking combined can increase the risks by 50 times.
Riboli acknowledged that the findings could prove confusing for patients who want to change their diet to protect against cancer.
``From the point of view of advice, one can only have one diet and it is better that the diet is globally healthy rather than aimed at just one particular cancer. It has to take into account other diseases, such as cardiovascular disease. It should not be focused on just one particular cancer but on health generally,'' he said.
``We continue to recommend that people have a diet which has a little bit of everything but a lot fruit and vegetables and not necessarily a vegetarian diet, that they eat dairy products and remain physically active, don't smoke and drink only in moderation,'' the researcher advised.
The study, which is ongoing, is not due to finish until at least 2003. But the research team is planning to publish a scientific paper examining the links between cancer and food in 2002.
High Fiber Diet Can Cut Cancer Risk by 40 Percent-Study
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Updated: Sat, Jun 23 6:34 AM EDT
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LONDON (Reuters) - A high fiber diet can slash the risk of developing deadly cancers by as much as 40 percent, scientists said Saturday.
Results from the biggest ever study into diet and cancer involving 400,000 people from nine countries, presented at an international conference in France, showed fiber was particularly important in reducing cancer of the colon and rectum.
"These are the first positive results for the benefits of fiber from such a large group. We placed 400,000 people on the study into five sets according to their consumption of fiber," Professor Sheila Bingham of the Dunn Human Nutrition Unit at Cambridge University said in a statement released in London.
"The group eating the most fiber reduced their risk of colorectal cancer by as much as 40 percent," she added.
The findings were part of the EPIC (European Prospective Investigation of Cancer and Nutrition) that was reported at the European Conference on Nutrition and Care in Lyon, France.
Medical experts believe up to 30 percent of all cancers in the developed world are associated with nutritional factors and could be avoided by better-balanced diets.
The EPIC study, which began 15 years ago, also showed a decreased chance of developing colon cancer in people eating lots of fish, but a raised risk in those consuming large amounts of preserved meats such as ham, bacon and salami.
People are advised to eat five portions of fruit and vegetables a day to achieve optimum health and avoid cancer.
Professor Nick Day said the landmark study should set the record straight on diet and cancer.
"There have been reports recently that appear to suggest fruit and vegetable consumption isn't important in reducing the risk of colorectal cancer," Day said.
"This wide-ranging study is likely to give us a much truer picture of the links between cancer and diet," he added.
The EPIC study also showed that people who smoke a packet of cigarettes a day and drink more than a bottle of wine are 50 times more likely to suffer from throat cancers.
Eating poultry did not increase the risk of cancer and may have a protective effect, according to the report.
"These finding are important because of the sheer scope of the EPIC study. They put fiber firmly back on the menu as an important part of a healthy diet," said Professor Gordon McVie, the director general of the Cancer Research Campaign, which sponsored Bingham's research.
The European Conference on Nutrition and Cancer, which began Thursday, is looking at the impact of different types of food on the disease.
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Plant Hormones Form Basis of New Anti-Cancer Drugs
Updated: Wed, May 23 7:29 AM EDT
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By Patricia Reaney
LONDON (Reuters) - A hormone used by plants to control their growth is being harnessed by British researchers to develop new targeted treatments for cancer, researchers said on Wednesday.
Plants need the hormone, called indole acetic acid (IAA), to bend shoots toward sunlight to help cuttings grow roots. Scientists at the Cancer Research Campaign, a leading scientific charity, are using fragments of IAA to kill cancer cells.
The hormone, which is produced by most plants, is harmless to humans. But, in early laboratory studies when scientists used bits of it and coupled them with an enzyme, it produced toxic by-products that destroyed cancerous tumors without harming healthy cells. "The fragmented molecule is only released in the tumor," Professor Peter Wardman told a news conference.
By targeting only the cancerous cells synthetic drugs based on IAA, called prodrugs, would be highly effective in killing the cancerous cells and would not produce side effects such as hair loss and nausea like conventional chemotherapy drugs.
"We're really excited that a common or garden plant hormone could fulfil one of the ultimate aims of cancer research, by providing a drug that only attacks cells and leaves the rest of the body untouched," Wardman, a scientist at the Gray Cancer Institutes in southern England, explained.
In laboratory studies of cell cultures Wardman and his colleagues used an enzyme called peroxidase, which is derived from the horseradish plant, to trigger the release of the toxic by-products of IAA to destroy tumors.
Early results show the treatment, which has been patented by the CRC, killed 99 percent of the cancerous cells and with different types of cancer. Scientists said tests will now have to be done on animals and humans.
"Nearly all of the cells are killed with a single treatment," said Wardman.
The scientists used the horseradish enzyme because it is cheap and well studied. It breaks up IAA into smaller chemicals which react with other molecules in the body to produce the toxins.
To direct the toxins only to the cancerous cells the scientists are using antibodies to tumour cells linked to the enzymes. Wardman said genetic technique could also be used to direct the therapy to the cancerous cells.
The scientists are also working on developing prodrugs that can be activated by light, similar to photodynamic therapy, which Wardman said could be used during surgery to kill any remaining cancer cells after the tumour has been removed.
"It's long been the ambition of cancer researchers to develop drugs that directly target the tumour, and thanks to these amazing plant hormones and a bit of nifty chemistry, we're now a step closer to that ideal," said Professor Gordon McVie, the director general of the CRC.
Health - Reuters - updated 5:43 PM ET May 21
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Monday May 21 5:38 PM ET
Apples, Tomatoes May Keep Lungs Healthy
By Steven Reinberg
SAN FRANCISCO (Reuters Health) - Eating plenty of apples and tomatoes may help prevent respiratory disease, according to a presentation here Sunday at the 97th annual meeting of the American Thoracic Society.
Dr. Emma Broadfield from the University of Nottingham, UK, and her colleagues used a test called forced expiratory volume 1 (FEV-1), which measures the amount of air a person can expel from his or her lungs in one second. They studied 2,633 adults in 1991 and again in 2000.
The investigators found an association between the intake of apples and tomatoes and increased FEV-1. When the researchers ''looked at that relationship of dietary intake of these foods across time, we saw a beneficial effect on lung function from apples and tomatoes,'' Broadfield said.
Eating more than five apples each week was strongly associated with increased FEV-1, as was having tomatoes more than three times a week. Wheezing was also less common among people who consumed apples, tomatoes and bananas, the findings indicate.
``Apples and tomatoes have high levels of antioxidants, and we suspect that what we are seeing is an antioxidant effect,'' Broadfield told Reuters Health. ``I think it all comes down to healthy eating is good for you,'' she added.
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Sources: yahoo newsReuters
Monday May 21 5:41 PM ET
 Home Treatment of Blood Clot in Leg Safe for Some
By Melissa Schorr
NEW YORK (Reuters Health) - Potentially dangerous blood clots in the legs, also known as deep vein thrombosis (DVT), can be treated safely and effectively at home in most cases with an injection of a new blood-thinning drug, a team of German researchers reports.
``Virtually no DVT patient has to be hospitalized for medical reasons,'' lead author Thomas Schwarz, a fellow in the division of vascular medicine at the University Hospital in Dresden, Germany, told Reuters Health. ``For selected patients, outpatient treatment has been shown to be safe and effective.''
The researchers followed patients who came to the hospital for treatment of DVT. Patients with DVT face the risk of having one of the clots dislodge and travel to their lungs--a potentially fatal condition known as pulmonary embolism. DVT treatment includes giving the patient drugs that dissolve the clots, or anticoagulants.
Traditionally, patients needed to remain in the hospital for intravenous administration of anticoagulant drugs such as heparin. But patients can inject themselves with a new form of the drug called low-molecular weight heparin, according to the report published in the May 19th issue of the British Medical Journal.
Of the 117 DVT patients who came to the hospital, 92 were sent home with instructions on how to inject the anticoagulant drug. These patients were also given compression stockings to wear, which squeeze the lower legs and reduce clot formation.
At a follow-up 12 weeks later, all of those patients had successfully treated themselves, with no episodes of major bleeding and no deaths due to pulmonary embolism. There were four cases of minor bleeding and three cases of recurrent blood clots.
Only 3% of the patients were required to remain for treatment in the hospital for medical reasons, such as severely swollen legs and acute pain. An additional 9% remained in the hospital for treatment because the researchers determined they did not have the social support necessary to receive adequate medical care at home.
The study was funded by medi-Bayreuth, makers of compression stockings, and by Sanofi-synthelabo, the global pharmaceutical company that manufactures the new form of heparin.
In an accompanying editorial, hematologist John Eikelboom of the Royal Perth Hospital in Australia and colleagues concurred that home treatment of deep vein thrombosis is now ``routinely feasible.''
However, they added, there are four types of patients who will remain ineligible for home treatment: those who have suffered a massive thrombosis; those at high risk of bleeding; those with variable needs for dosage such as children or pregnant women; and those with specific medical disorders that require hospital admission.
Finally, the editorialists noted, because deep vein thrombosis is potentially fatal, ``some patients will inevitably die during home treatment.... The safety and effectiveness of home treatment programmes in individual centres need to be monitored.''
SOURCE: British Medical Journal 2001;322:1192-1193, 1212-1213.
Lactobacillus Administration to Infants May Reduce Risk of Early Atopic Disease
WESTPORT, CT (Reuters Health) Apr 05 - Children from families with a history of atopic disease may be protected from these diseases by giving them the probiotic Lactobacillus GG early in life, according to a report published in the April 7th issue of The Lancet.
Dr. Marko Kalliomaki, from Turku University Hospital, in Finland, and colleagues randomized 159 mothers who had at least one first-degree relative or partner with atopic eczema, allergic rhinitis or asthma to receive daily placebo or Lactobacillus GG capsules 2 to 4 weeks prior to expected delivery. After delivery, breast-feeding mothers and children of nonbreast-feeding mothers continued the assigned therapy for 6 months.
Of the 132 children who completed the 2-year study, 46 were diagnosed with eczema, "the main sign of atopic disease in the first years of life.". Six of these children also met diagnostic criteria for asthma and one child met criteria for allergic rhinitis.
The researchers found that children who received the probiotic were half as likely as placebo-receiving children (235 vs. 46%) to develop atopic eczema.
"Our results suggest that gut microflora have unique, yet largely unexplored, endogenous immunomodulatory properties," the investigators note. "These properties might be indispensable in the fight against the increasing frequency of atopic, and possibly other, immunologic diseases."
"As in comedy, the secret of successful immunotherapy may be timing," states Dr. Simon H. Murch, from the Royal Free and University College School of Medicine, in London, in a related editorial. The improvement noted in the current study was "greater than usually seen with probiotic administration later in life, and larger studies will be required before these agents can be more widely recommended for perinatal use," he adds.
Lancet 2001;357:1057-1059,1076-1079.
Study: Soy Helps Even with Normal Cholesterol
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WASHINGTON (Reuters) - Even people with normal levels of cholesterol can benefit from eating more soy because it boosts levels of so-called good cholesterol, researchers said on Friday.
Heart experts said the study supports their advice that Americans replace at least some artery-clogging meat and dairy foods with soy protein.
Healthy people who ate food with extra soy protein, such as baked items made with soy flour, saw their high density lipoprotein (HDL or good) cholesterol go up while levels of low density lipoprotein (LDL or bad) cholesterol stayed down.
"Our study demonstrates that, in a population with normal cholesterol levels and low dietary protein intake, soy protein increases HDL in the bloodstream, but does not significantly alter LDL," Dr. Jiang He of Tulane University School of Public Health and Tropical Medicine in New Orleans, who led the study, said in a statement.
He, who presented his team's findings to a meeting of the American Heart Association in San Antonio, tested 60 men and 90 women in China, aged 35-65, all of whom had normal cholesterol levels.
"People in China usually consume a low-protein diet and get little animal protein," He said. This makes them less likely to develop high cholesterol and heart disease in the first place.
He's team fed half of them biscuits containing soy protein supplements every day, and half were given a different biscuit.
Three months later, those who ate the soy showed on average a 4.7 percent increase in HDL, which carries artery-clogging fat out of the blood vessels for disposal.
The American Heart Association last year recommended that everyone eat more soy, and said this study supports its position. Several studies have shown that adding soy protein to the diet can help people lower high cholesterol -- especially if it replaces meat and cheese.
"There is increasing evidence that consumption of soy protein in place of animal protein lowers blood cholesterol levels and may provide other cardiovascular benefits," the association's Nutrition Committee said in a statement.
"Most bean proteins are good for health," He said. "However, soybean protein is the only one that has been documented to affect cholesterol levels by clinical trials conducted in western countries."
Most Americans get more protein than they need anyway. Human beings need to get only 15 percent of calories from protein. But soy is considered a "complete" protein that has all of the nutritional benefits of meat.
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Botox Stops Sweat
The deadly botulism toxin may offer another health benefit - it
may help people who sweat excessively to stay drier. A German
study published in the New England Journal of Medicine finds that
injections of botulism toxin can control hyperhidrosis, a
condition that causes sufferers to sweat very heavily. Botox is
already used to help smooth wrinkles and to relieve the pain of
persistent neck spasms. In the new study, researchers from the
University of Munich doctors injected diluted toxin into the
armpits of 145 hyperhidrosis patients. At the start of the
study, the patients produced about four cups of sweat every eight
hours. Two weeks after they received the injections, they
produced only 15 percent of that amount, The Associated Press
reports. The researchers say the toxin, which blocks the release
of a chemical that transmits nerve signals to the sweat glands,
appears to work better than the other therapies available.
However, the effects of the treatment are temporary; after two
weeks patients gradually began sweating more heavily. The
injections, which have to be repeated every three to six months,
are also expensive and the long-term risks of nerve damage or
allergic reactions from them have not yet been determined, the AP
says.
Backpack Burdens
Middle school kids may be headed for back problems, thanks to
their overloaded backpacks. Research to be presented at the
American Physical Therapy Association conference finds that many
fifth- through eighth-graders carry backpacks that are too heavy
for their body size. The study, which looked at 354
Massachusetts children, found that 55 percent of the children
surveyed carried around backpacks that weighed more than 15
percent of their body weight. One-third of the students said
they experienced back pain. Earlier research has found that
wearing a backpack on one shoulder may increase the risk for
scoliosis, The Associated Press reports. The study's author says
that having schools give extra textbooks so students don't have
to carry as many home, issuing texts on CD-ROM instead of books
and using better-designed ergonomic backpacks may kids avoid back
problems, according to the AP.
For more on children's health, go to: http://www.intelihealth.com/IH/ihtIH/EMIHC000/20722/20722.html
Low Fat Diet And Stroke
Too much saturated fat is bad for your health, but in some people
too little may also pose a health risk. A study published in the
American Heart Association journal Circulation finds that women
who follow an extremely low fat diet have a higher risk for a
rare type of stroke than women who consume a more moderate
reduced-fat diet. In the study, researchers from the Harvard
School of Public Health looked at data on the women participating
in the large-scale, ongoing Nurses' Health Study between 1980 and
1996. The researchers found that the women who consumed the
least saturated fat, about 20 grams per day, were twice as likely
to have a type of hemmorhagic stroke called intraparenchymal
hemorrhage than women who ate 25 to 36 grams of saturated fat per
day. The researchers found that of 690 strokes that occurred in
the group they studied, nearly 11 percent were intraparenchymal
hemorrhages. The increased stroke risk was mainly seen in women
with high blood pressure, The Associated Press reports. The
researchers say their findings suggest that extremely low fat
intake combined with high blood pressure may weaken blood
vessels, increasing the chance that they will rupture. The
researchers emphasize that cutting back on the amount of
saturated fat in your diet is still a good idea, but that this
should be done in moderation. Although the study looked only at
women, the researchers say the findings probably apply to men as
well, the AP says.
For more on nutrition, go to: http://www.intelihealth.com/IH/ihtIH/EMIHC000/325/325.html
For more on stroke, go to: http://www.intelihealth.com/IH/ihtIH/EMIHC000/8772/8772.html
For more on high blood pressure, go to: http://www.intelihealth.com/IH/ihtIH/EMIHC000/8315/8315.html
EMBARGOED FOR RELEASE: 13 DECEMBER 2000 AT 08:00 ET US Cedars-Sinai Medical Center
Irritable Bowel Syndrome may be linked to the presence of excessive bacteria in the small intestine
LOS ANGELES, Ca.- Researchers at Cedars-Sinai Medical Center may have identified the cause of Irritable Bowel Syndrome (IBS), a gastrointestinal condition that afflicts about 20 percent of the adult population and is diagnosed in twice as many women as men. The findings, published in the December issue of The American Journal of Gastroenterology, may shed new light on how to treat the symptoms of bloating, abdominal pain, diarrhea and/or constipation associated with IBS.
“Our research shows that the majority of patients we evaluated with IBS had excessive bacteria in the small intestine and that treatment with antibiotics greatly reduced the gastrointestinal symptoms of this condition,” said Dr. Mark Pimentel, the principal investigator of the study and Assistant Director of the Cedars-Sinai GI Motility Program.
In the study, the investigators evaluated 202 patients who underwent a specialized breath test to determine the presence of small intestinal bacterial overgrowth (SIBO), a condition in which excessive quantities of bacteria are present in the small intestine. The researchers found that SIBO was present in 78 percent of the patients tested.
“The fact that SIBO was found in the majority of patients we tested with IBS suggests a strong association between the two conditions,” said Dr. Pimentel.
To determine whether eliminating SIBO from the small intestine would improve the symptoms of IBS, patients who tested positive for excessive bacteria were subsequently treated with antibiotics for 10 days. Among these patients, 47 returned for a follow-up breath test approximately 10 days after they completed treatment with the prescribed antibiotic. The breath tests were subsequently analyzed for the presence of SIBO. The investigators found no SIBO present in 25 of these patients, while some SIBO was still detected in 22 of the patients as indicated by the breath test.
“On the whole, we found a significant reduction in the symptoms of IBS even in those patients in which SIBO was only partially eradicated,” said Dr. Pimentel, noting that an alternative antibiotic may have been necessary to completely eliminate SIBO in these patients.
Among the 25 patients in which no SIBO was detected after treatment with antibiotics, 12 reported no symptoms of IBS whatsoever, while the symptoms of IBS were found to be significantly reduced in the remaining 13 patients.
The symptoms were also reduced in the patients in which some SIBO was still detected after completing the 10-day course of antibiotics, suggesting that treatment to the point in which SIBO was completely eliminated could have achieved better results.
“This is the first study to demonstrate that complete eradication of SIBO with commonly prescribed antibiotics substantially improves the symptoms of IBS, especially those associated with bloating, diarrhea and abdominal pain,” said Dr. Henry C. Lin, senior author of the study and Director of the Cedars-Sinai GI Motility Program.
Currently, the investigators are conducting follow-up studies to determine how long some patients need to be treated to completely eliminate SIBO. To prevent patients from developing a resistance to antibiotics, the investigators plan to test novel non-antibiotic therapies in future clinical trials.
MMR Vaccine Linked to Blood Disorder
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Updated 7:01 PM ET February 22, 2001
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NEW YORK (Reuters Health) - British researchers have confirmed that the measles-mumps-rubella (MMR) vaccine can cause a rare bleeding disorder in children.
But they stress that children remain at much higher disease risk from measles, mumps or rubella if they forego vaccination, than they are from the vaccine-linked bleeding condition, called idiopathic thrombocytopenic purpura (ITP).
People with ITP bleed under the skin, causing a kind of purple bruise to spread across the body. Other symptoms can include tiny red spots on the skin and nosebleeds. The condition is mild in the majority of cases.
The reaction, caused by the destruction of the platelets that help blood clot, seems to occur most often within the first 2 or 3 weeks of receipt of the vaccine according to the American Academy of Pediatrics. In their "Red Book" of childhood diseases, they describe the thrombocytopenia caused by the MMR vaccine as "transient and benign."
The vaccine has been linked to the disease for years, although evidence supporting the association has been limited.
In the current study, published in the March issue of the journal Archives of Disease in Childhood, researchers evaluated records at two hospitals in England between 1991 and 1994.
They verified records for 21 children between 12 and 23 months admitted with ITP, of whom nine were admitted within 6 weeks of having the MMR vaccine.
Based on this, Dr. Elizabeth Miller of the Communicable Disease Surveillance Center in London and colleagues calculated that "the absolute risk (of hospitalization for ITP) within six weeks of immunization was 1 in 22,300 doses."
ITP can occur in children following a viral infection. Miller and colleagues note that the vaccine-related risk is quite low when compared to ITP that occurs after catching measles, rubella or mumps. For instance, one case of ITP occurs for about every 3000 rubella infections.
Cases linked to the vaccine were also milder than those resulting from the viral diseases, and resulted in shorter stays in hospital, Miller's group reports.SOURCE: Archives of Disease in Childhood 2001; 84: 227-229.
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COX-2 AND CANCER
COX-2 Inhibitors and Cancer Chemoprevention CME
This activity is not sanctioned by, nor a part of, the American Society of Clinical Oncology 36th Annual Meeting. The materials presented here were prepared by independent authors under the editorial supervision of Medscape, Inc., and do not represent a publication of the American Society of Clinical Oncology. These materials and the related activity are not sanctioned by the American Society of Clinical Oncology or the sponsors of the conference, and do not constitute an official part of that conference. Bernard Levin, MD, Robert Mocharnuk, MD http://www.medscape.com/Medscape/oncology/TreatmentUpdate/2000/tu10/public/toc-tu10.html
Table of Contents
 Introduction
 COX-2 and Colorectal Cancer
 The COX Family
 COX-2 in Familial Adenomatous Polyposis
 Why COX-2 Inhibition Is Safer
 COX-2 and Prevention/Treatment of Other Cancers
 COX-2 Inhibitors and Supportive Care
 Conclusions
Introduction
"Take an aspirin and call me in the morning" defines the term "medical cliché" but may have much more to do with cancer prevention and treatment than previously imagined. COX (cyclooxygenase)-2 inhibitors, close relatives to aspirin, have been in the news for at least the past year with respect to their anti-inflammatory properties for treatment of refractory arthritic disease as well as for pain management. But, like most things, there is much more to the COX-2-inhibitor story than inflammation or pain control. In a symposium held before this year's American Society of Clinical Oncology meeting in New Orleans, Louisiana, the broader scope of COX-2 inhibition was discussed by leading clinical researchers in light of the latest findings and clinical data.
COX-2 and Colorectal Cancer
The Scope of the Problem
Dr. Raymond DuBois, Director of the Vanderbilt Ingram Cancer Center for Cancer Prevention as well as Director of Gastroenterology, Hepatology, and Nutrition at the Vanderbilt University Medical Center in Nashville, Tennessee, opened the proceedings by focusing on the role of COX-2 inhibition in the development of colorectal cancer. Whereas the incidence of colorectal cancer varies greatly throughout the world, it is particularly common in North America and Western Europe as well as in Australia and New Zealand. This higher incidence may be of special importance because of the high rate of red meat consumption in these countries. In general, the highest incidence of colorectal cancer is found in industrialized areas and approximately 8.5% of all newly diagnosed cases of cancer worldwide are colorectal in nature. This translates into 850,000 newly diagnosed cases of colorectal cancer worldwide in 1999 and 556,000 deaths.
In the United States, approximately 130,000 new cases of colorectal cancer were diagnosed in 1999 with 57,000 colorectal cancer-related deaths. Most patients (93%) were more than 50 years of age. Colorectal cancer remains the third most common malignancy and the second most common cause of death from cancer in this country. The cost from hospitalization is much greater among colorectal cancer patients than among breast, lung, or prostate cancer patients.
Interestingly, those groups of individuals at lower risk for colorectal cancer in their native countries appear to develop the high risk of occurrence found in those countries to which they have emigrated. This has been studied previously among Japanese emigrants who relocated to Hawaii. Within a generation's time, their risk of contracting colorectal cancer was the same as those of endogenous Hawaiians. This would imply that in addition to genetic factors, lifestyle and behavior must play an important role in the pathogenesis of this disease. Individual differences exist among ethnic groups; for example, the 5-year overall survival rate among whites is higher (63%) than blacks (52%).
Risk factors for colorectal cancer include:
 age older than 50 years
 a history of colorectal adenomas
 a history of breast, ovarian, and uterine cancer, especially at a younger age
 a familial history of colorectal cancer or adenomas, especially before age 60
 familial hereditary syndromes, including familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), and hamartomatous polyposis
Colorectal Tumorigenesis
Colorectal cancer evolves through a multistep process in which some genes are activated, such as the oncogene Ras, whereas others, such as the tumor suppressor genes APC (adenomatous polyposis coli) and p53, are inactivated. APC gene mutations are inherited in FAP, although APC loss does occur in as many as 80% of sporadic colorectal tumors. HNPCC syndromes are associated with the early onset of cancer and appear to stem from defects in DNA mismatch repair mechanisms. Carcinogenesis takes place during a 15- to 25-year period, beginning with APC mutations in all FAP patients and most sporadic colorectal cancers, resulting in loss of heterozygosity and leading to the development of early adenomas. This is followed by mutations in the K-ras oncogene that lead to loss of chromosome 18 and the production of late-stage adenomas. Thereafter, p53 mutations eventually result in the development of colorectal tumors. Carcinogenesis in HNPCC syndromes as well as in 15% of sporadic cases of colorectal cancer begins with mismatch repair mutations, leading to microsatellite instability and resulting in defects in the TGF (tissue growth factor)-beta type II receptor and BAX signaling pathways. It is likely that other pathways for colorectal tumorigenesis remain to be elucidated.
The COX Family
Since colorectal carcinomas develop over a period of many years, tumor prevention has been a subject of great interest. Previous epidemiologic data have elucidated aspirin's role in reducing by about 40% to 50% the incidence of polyps in large patient populations.[1] More importantly, these same studies have shown an up to 50% decrease in colorectal carcinoma mortality, directly attributable to the use of aspirin or nonsteroidal anti-inflammatory agents (NSAIDs).[2] Dr. Frank Giardiello and colleagues[3] have demonstrated in a randomized clinical trial that sulindac given twice daily (150 mg twice a day) for 9 months led to a significant reduction in the number and size of polyps in patients with FAP, when compared with placebo. When the drug was discontinued, both the number and size of polyps increased.
Many theories have been advanced to explain the mechanisms of action behind the efficacy of aspirin and NSAIDs. One clearly established route is via the inhibition of COX enzymes. There are currently 2 COX isoforms: COX-1 and COX-2. COX-1 serves primarily as a "housekeeping" enzyme and is made throughout the gastrointestinal (GI) tract. It also plays an important role in the maintenance of renal function and is found in platelets and vascular endothelium. COX-2 is primarily inducible, stimulated by numerous inflammatory mediators, cytokines, and tumor promoters. Conversely, COX-2 is inhibited by steroids. It appears to be made in the kidney as well as in the central nervous system, and it also plays a role in fertility during blastocyst implantation and ovulation.
Under normal physiologic circumstances, COX-2 is expressed in the GI tract at undetectable levels, but this expression rises significantly in the presence of colorectal malignancies.[4] In one study, overexpression of COX-2 was noted in 85% of 150 individuals with documented colorectal adenocarcinomas, with increases in COX-2 expression ranging from 2- to 50-fold.[5] Among 40 patients with benign colorectal adenomas, COX-2 was elevated in 40% to 50% of the tumors. No significant change in COX-1 expression was noted in either benign or malignant tumors.
Background Research on COX-2 Inhibition
The reason for COX-2 overexpression has not been determined. The gene that codes for COX-2 has not been shown to mutate. Neither have changes in the promoter of the COX-2 gene been identified. Recent work by Sheng and colleagues[6] in animal models has suggested that colorectal tumors expressing a Ras mutation express significant amounts of COX-2. This is of note since Ras mutations are involved in the production of late stage adenomas and eventual loss of chromosome 18.
In vitro studies. Sheng and colleagues[7] have also published some interesting work concerning individual colorectal cancer cell lines HCA-7 and HCT-116. HCA-7 cells express high levels of COX-2, while HCT-116 cells lack COX-2 expression, likely due to genomic instability. Those cells that produce COX-2 have been shown to express high levels of prostaglandin (PGE2), whereas HCT-116 cells lack PGE2 expression. Furthermore, when a selective COX-2 inhibitor (SC58125) was added in increasing concentrations to in vitro cultured cells, it induced growth inhibition of HCA-7 but not of HCT-116 colon cancer cells.
Animal studies. When these same HCA-7 cells were grown in nude mice, an 85% to 90% xenograft suppression was achieved with daily administration of the selective COX-2 inhibitor celecoxib compared with no growth suppression with administration of placebo.
Dr. DuBois presented unpublished data showing that treatment delayed at even 7 weeks after tumor implantation, with either the COX-2 inhibitor SC 58125 or the nonselective NSAID sulindac sulfide, resulted in a dramatic decrease in tumor growth, compared with placebo. Interestingly, tumor regression was not observed, but growth suppression was sustained for 8-12 weeks after discontinuation of either SC 58125 or sulindac. The same effects were observed when treatment with celecoxib was initiated at various increments of delay. Follow-up investigations have shown that downstream gene expression is affected in these growth-arrested tumors.
The importance of COX-2 expression and inhibition in colorectal tumorigenesis has been evaluated in several other animal models. Williams and coworkers[8] have shown that COX-2 is overexpressed in tumors in Min mice and that tumor growth was suppressed by COX-2 inhibitors. Oshima and colleagues[9] at the University of Tokyo studied mice with induced APC mutations that subsequently developed polyps ranging in number from 6-800. When these mice were crossed with a strain of mice lacking the COX-2 gene (the so-called COX-2 null mice), there was a significant decrease in the number of polyps in their progeny. Moreover, in those few COX-2 null mice in which polyps grew, the polyps tended to be much smaller and more poorly developed than those from wild-type mice. When these same mice were treated with MF tricyclide, a precursor to rofecoxib, a dramatic decrease in the number of polyps was observed. Jacoby and colleagues[10] at the University of Wisconsin have published data comparing the use of celecoxib vs piroxicam, another NSAID, in Min mouse tumors. Independently of whether the animals were treated early or late after development of polyps, a significant reduction in polyp number was observed, and no statistical differences were observed between celecoxib- or piroxicam-treated animals.
COX-2 expression was evaluated in rat tumors by DuBois and colleagues 1 year following administration of carcinogen-inducing azoxymethane (AOM).[11] The levels of intratumoral COX-2 were significantly elevated compared with normal adjacent mucosal tissue. Conversely, there was no difference in COX-1 expression in benign or malignant tissue. Employing these same tumor models, Kawamori and colleagues[12] exposed rats to a number of NSAIDs as well as to celecoxib. They reported that inhibition of tumor formation was much greater in those rats exposed to the selective COX-2 inhibitor and admittedly had more problems with the administration of nonselective NSAIDs due to their inherent toxicities. No significant toxic effects were observed with the use of celecoxib. This reduction in tumorigenesis applied to both nonmalignant adenomas as well as to invasive and noninvasive adenocarcinomas.
COX-2 and Angiogenesis
Dr. Folkman[13] observed that the ability of a carcinoma to induce angiogenesis is fundamental to tumor growth beyond 2-3 mm. Ongoing research at Vanderbilt University is attempting to define the role of COX-2 in angiogenesis as it relates to the biology of endothelial cell growth. Using techniques adapted from other research centers, investigators at Vanderbilt have employed a 2-chamber migration assay with placement of type I collagen and endothelial cells in the upper chamber and placement of colorectal carcinoma cells in the lower chamber.
The level of COX-2 was then modulated within the colorectal carcinoma cells and subsequently analyzed with respect to its impact on endothelial cells in the upper chamber. Using COX-2-rich HCA-7 and specially programmed Caco-2 colorectal cells designed to overexpress COX-2, it was noted that endothelial cell migration to the bottom layer of the upper chamber was high when compared with non-COX-2-expressing Caco-2 control cells. The addition of a selective COX-2 inhibitor (NS-398) induced a dose-dependent decrease in the amount of endothelial cell migration. The same effect was observed after the administration of aspirin. Subsequent studies have confirmed that COX-2 does indeed play a role in the upregulation of tumor angiogenesis.
Key Points: An Interim Review
 COX-2 expression is upregulated during intestinal tumorigenesis and by tumor promoters
 Modulation of COX-2 expression affects tumor number
 Treatment with COX-2 inhibitors reduces tumor number
 COX-2 may be a relevant target for prevention and/or treatment of colorectal cancer and clinical trials are under way to test this hypothesis
COX-2 in Familial Adenomatous Polyposis
Dr. Bernard Levin, Vice President of Cancer Prevention at the M. D. Anderson Cancer Center in Houston, Texas, reiterated the fact that aspirin and NSAIDs have indeed been shown to decrease the incidence of colorectal adenomas as well as adenocarcinomas. He suggested that long-term nonsteroidal use will eventually change the incidence of colorectal carcinomas as it has already begun to reduce colorectal cancer mortality. Substantial data already exist on the effect of NSAIDs in FAP. In 15 uncontrolled trials involving more than 100 patients as well as in 3 controlled trials, results show both reduction and regression in the number and size of colorectal adenomas, although most of these responses are partial.
Chemoprevention of Colorectal Cancer
Despite the encouraging findings, many questions remain to be answered. In addition to requiring more broad-based, randomized, double-blinded trials, physicians have questions regarding the most appropriate agent to use, the correct dose, the optimal treatment duration, and the most appropriate criterion for selection of high-risk patients.
Benefits and Risks
Due to potential toxic effects, the benefits of disease prevention must be weighed against the risks of treatment. In particular, nonselective COX inhibitors pose substantial risks for GI bleeding and ulcer formation with subsequent hospitalizations as high as 3-fold when compared with controls. Currently, ongoing research at the National Cancer Institute (NCI) is attempting to address these concerns as well as others, such as the ideal route of COX inhibitor administration, and the use of agents like sulindac sulfone, which seems to function in some form other than COX-2 inhibition. Investigators are also looking at combining COX inhibitors with other agents, such as selenium, nontoxic bile salts, and retinoids.
Clinical Trials
Generally speaking, to optimize the effectiveness of ongoing research, clinical models should include cohorts with high penetrance of the target lesion or gene abnormality in question. These models should have end points that are likely to occur within short periods of time. In addition, accessible as well as multiple target organs make for more accurate assessment following treatment. Finally, current treatment methods fall short of ideal disease management, thereby motivating individuals to enroll in studies for the purpose of morbidity and mortality reduction, in addition to all the data such enrollment provides those conducting the studies. FAP appears to fit the ideal study target in many respects.
FAP
FAP disease symptoms include rectal bleeding, change in bowel habits, and abdominal pain. The average patient age at time of diagnosis is 36 years. Virtually 100% of patients will develop colorectal cancer by the age of 50 and the average age of death is 42 years. The number of adenomas correlates with increasing cancer risk as described previously. COX-2 expression in FAP is high.
Current management of FAP is primarily surgical, with colectomy and ileorectal anastamosis, followed by life-long rectal surveillance vs proctocolectomy with formation of an ileal pouch and anal anastamosis. Despite standard screening, prophylactic colorectal surgery, and careful endoscopic surveillance, the risk of death from colorectal cancer remains 3.5 times higher than the general populace. Surgery also increases the risk of morbidity, with higher rates of fecal incontinence among patients undergoing anal anastamosis and increased rates of sexual dysfunction secondary to dissection involved in rectal surgery. Therefore, a drug that could potentially enable patients to delay surgery or perhaps avoid it all together would be particularly appealing to many individuals with FAP.
Multi-institutional Randomized Trial with Celecoxib
Celecoxib was administered to patients with FAP in an NCI clinical trial. A total of 77 patients were randomized at the M. D. Anderson Cancer Center in Houston, Texas, as well as at St. Mark's Hospital in London, England, to receive either celecoxib or placebo.[14] Patients with both genetic and clinical evidence for FAP, an intact colorectal segment, 5 polyps of at least 2 mm in size, and a willingness to remain off all NSAIDs for a period of 6 months were included. Exclusion criteria included individuals with a history of gastric ulcers, complete colectomy, prior partial colectomy within 12 months, and an established diagnosis of colorectal cancer. Patients were matched for a number of pertinent characteristics except for a slightly lower mean age group (33 years) in the subset receiving the highest daily dose of celecoxib compared with 39 and 40 years in other treatment arms. Evaluation was performed after 6 months of treatment for number of polyps, polyp size, and biomarker analysis, such as COX-2 expression, tissue prostanoid quantification, and proliferative index.
Among 32 patients who received 100 mg twice a day of celecoxib, there was a 14.6% reduction in the number of colon polyps, compared with a 4.9% reduction in the 15 patients given placebo. When the dose of celecoxib was increased to 400 mg twice a day in 30 patients, there was a 30.7% reduction in polyp burden (sum of polyp diameters) (P = .001). Reduction in polyp size was measured carefully using anatomic landmarks, photographs, and tattoos, all of which held up to rigorous analysis and were readily reproducible. Endoscopic assessment was performed by blinded endoscopists and was subject to subsequent independent review.
A decrease in the area of duodenal polyps was observed in 1.4% of the 12 patients given placebo, 4.2% of 21 patients who received 100 mg twice a day of celecoxib, and 14.5% of 17 patients who received 400 mg twice a day (P = .436). Reduction in polyp number and size was seen throughout various segments of the small and large intestine, including the duodenum, regarded as a particularly difficult area to treat with conventional methods. There were no significant differences in toxicity observed between the celecoxib and the placebo groups. The medication was well tolerated, and this study echoes the adverse effect findings listed on the drug insert for treatment of osteoarthritis and rheumatoid arthritis.
Importance of Celecoxib in the Management of FAP
Based on these results, the Food and Drug Administration (FDA) approved celecoxib for use as an adjunct in the treatment of FAP in December 1999. While impressive, celecoxib is not a replacement for endoscopic surveillance or for surgery. Neither is it known how long the benefits of celecoxib persist after discontinuation of the drug.
So, if celecoxib cannot replace endoscopy or surgery in the management of FAP, what are its potential clinical benefits? To begin with, decreasing the number and size of polyps may improve the efficacy of endoscopic surveillance. Celecoxib may delay FAP-related surgery, a critical issue for many of these patients who often require surgical intervention during high school or college. Delay or reduction of duodenal surgery is particularly important because of its critical role in digestion and pancreatic function. The most exciting potential benefit of celecoxib may be the prevention of FAP in those young individuals who are genotypically predisposed to develop it. Administering celecoxib before the onset of polyp development could prevent the disease from ever being clinically expressed.
This trial is important because it offers, for the first time, an adjunctive pharmacologic approach to the management of patients with FAP. Even more important is the fact that this trial serves as a stimulus for additional research in FAP, which often is overlooked because it is responsible for only 1% of all colorectal neoplasias. Interestingly, the FDA approval of celecoxib for prevention of FAP was based on a preinvasive neoplastic end point, a first in FDA oncologic annals and one that is likely to be repeated in the not too distant future. From a purely financial point of view, this sends a strong message to the pharmaceutical industry that investing in chemoprevention may indeed prove to be worthwhile.
COX-2 inhibition and FAP is only one of many preventive applications for this class of drugs. It has been established previously that aspirin has activity against cardiovascular disease, cancer, and arthritic pain. Current investigations are looking at aspirin's role in the prevention of Alzheimer's disease and osteoporosis. COX-2 inhibitors are already being evaluated in an NCI-sponsored study through Harvard University and other centers to determine whether celecoxib prevents adenomas from recurring after polypectomy. The impetus for this study stems from the high rate of polyp recurrence, the numerous endoscopic procedures required to screen for these polyps, and the economic gain that could be attained if subsequent colorectal cancer could be prevented.
Why COX-2 Inhibition Is Safer
Dr. Andrew Dannenberg, Director of Cancer Prevention at New York Presbyterian Hospital and Professor of Medicine and Surgery at the Weil Medical College of Cornell University in New York, broadened the scope of COX-2 inhibition to include other than GI-related malignancies. He began by expanding the previous discussion on the toxicity profile of COX-2 inhibitors. When considering therapy for cancer prevention, it is important to identify as accurately as possible the population at risk for any given malignancy. For individuals who are at low risk for cancer, any preventive therapy must be extremely safe. This is reflected in previous recommendations, such as low-fat diets and calcium supplementation.
For those individuals at high risk for such cancers as FAP, patients as well as investigators are willing to accept more risks in their choice of preventive measures. Because of the remarkable safety profile of COX-2 inhibitors, it is possible that these agents can be used in low-, moderate-, and high-risk patients without having to factor in safety concerns. In contrast, NSAIDs have previously been shown in a series of epidemiologic studies to decrease the relative risk of colorectal as well as lung and breast cancers. Despite these results, NSAIDs have not been widely used in the prevention of tumorigenesis, primarily because of toxicity concerns.
Toxic Effects of NSAIDs
Because NSAIDs inhibit both COX-1 and COX-2, patients develop higher rates of peptic ulcer, a problem that causes an estimated 100,000 hospitalizations and 16,500 related deaths per year in the United States. As indicated previously by Dr. DuBois, COX-2 inhibition is specific, unlike NSAIDs. The therapeutic utility of NSAIDs, just like COX-2 inhibitors, results from the inhibition of the inducible COX-2 enzyme. Unlike selective COX-2 inhibitors, NSAIDs inhibit the constitutively expressed COX-1, leading to higher rates of GI mucosal damage. The high levels of prostaglandin noted previously by Dr. DuBois among patients treated with both NSAIDs and COX-2 are likely mediated by the conversion of arachadonic acid. The GI mucosa housekeeping function of COX-1 is also most likely mediated by conversion of arachadonic acid.
Specific Inhibition of the COX-2 System
In the inducible COX-2 system, arachadonic acid is converted to prostaglandins, which are involved in the occurrence of the pain, inflammation, and fever common to arthritic joints. It is also thought that prostaglandins are involved in the mediation of tumor growth. The molecular structures of COX-1 and COX-2 differ at amino acid 523, where the former contains an isoleucine, the latter a valine. The presence of valine allows for methylation, which leads to a type of "side pocket" formation in COX-2. It is this methylated side pocket that has been targeted during development of COX-2 inhibitors, resulting in the design and production of celecoxib, followed shortly by rofecoxib. A review of each drug's toxicity profiles indicates that there is little difference between these 2 compounds. Both COX-2 inhibitors showed a similar rate of ulcer formation when compared with placebo.[15] In contrast, the rate of ulcer formation was significantly higher with naproxen use.
The increased risk of bleeding associated with NSAIDs, beyond that one caused by mucosal ulceration, relates to the presence of COX-1 in platelets. Because COX-1 is involved in platelet stabilization and activity, it stands to reason that inhibition of COX-1 impairs platelet function and integrity of platelet. The selectivity of COX-2 inhibitors does not disturb constitutive COX-1 activity, and therefore, far fewer episodes of bleeding are observed with celecoxib when compared with NSAIDs.
COX-2 and Prevention/Treatment of Other Cancers
The mechanisms by which COX-2 inhibitors are involved in tumor prevention have been elaborated on to some degree by both Drs. DuBois and Levin. Beyond prostaglandin upregulation (especially PGE-2) and anti-angiogenesis, COX has also been shown to convert procarcinogens to carcinogens, thus initiating tumor formation. This pathway could be important in understanding the pathogenesis of tobacco-related tumorigenesis. It is also known that COX-2 overexpression inhibits programmed cellular death (apoptosis).
Esophageal Cancer and COX-2
Since COX-2 affects so many components of tumor formation, it follows that COX-2 inhibition should exhibit activity in prevention and treatment of noncolorectal tumors. Data from Dr. Wilson and colleagues published in Cancer Research in 1998 demonstrated that COX-2 overexpression occurs in Barrett's esophagus as well as in adenocarcinomas arising from Barrett's esophagus.[16] Dr. Shirvani and associates[17] also demonstrated that COX-2 is not expressed in normal squamous esophageal epithelium. Because of these findings, a clinical trial of celecoxib in patients with Barrett's esophagus has just been initiated at Johns Hopkins in Baltimore, Maryland.
COX-2 in Head and Neck Cancer
Dr. Dannenberg reported on his own research group's work with COX-2 in squamous cell carcinoma of the head and neck (HNSCC). Historically, it has been known that prostaglandin levels are increased in HNSCC, compared with adjacent normal tissue. Moreover, is it also known that nonselective NSAIDs protect laboratory animals from HNSCC. The link between COX-2 overexpression and increased amounts of prostaglandin remained to be established. Dannenberg and colleagues used quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to measure COX-2 messenger RNA (mRNA) in 24 patients with head and neck cancer and compared these results with measured COX-2 mRNA levels in 17 control patients. A 150-fold increase in COX-2 mRNA levels was found among the squamous cell carcinoma patients. Normal tissue adjacent to malignant mucosa was also assayed for COX-2 mRNA and was found to have a 50-fold higher level of expression than normal oral mucosa. Moreover, oral leukoplakia, a precancerous lesion, was also found to express COX-2 protein. These results will serve as the basis for a clinical trial to be initiated in the near future evaluating the role of celecoxib in premalignant head and neck conditions.
The COX-2 Connection in Breast Cancer
Breast cancer and COX-2 overexpression have also been studied at Cornell University. Dr. Dannenberg and associates evaluated COX-2 expression as a function of HER-2/neu receptor status. In 29 cases of human breast cancer, 15 were found to be HER-2/neu positive. Of these, 14 were COX-2 positive. Four of the 14 HER-2/neu-negative breast cancer cases showed COX-2 expression, and at levels much lower than HER-2/neu positive patients. In separate work, human mammary epithelial cells have been shown to overexpress COX-2 via HER-2/neu-activated transcription. Whether this is merely an epi-phenomenon or a potential target for preventive therapy is not known.
Research done at Ohio State University investigated whether celecoxib can protect against experimentally induced breast cancer.[18] After chemically inducing breast cancer in 3 laboratory rats, ibuprofen and celexocib were administered in a sequential fashion and analyzed separately. The results indicated that the incidence of breast cancer was dramatically reduced by treatment with either compound, suggesting that COX-2 inhibition may be a useful adjunct in both breast cancer treatment and breast cancer prevention.
Bladder Carcinoma and COX Overexpression
The Cornell research team has also determined that COX-2 is overexpressed in both in situ and invasive transitional cell bladder cancers in 10 of 10 patients studied. Animal studies have shown that the addition of the COX-2 inhibitor, nimesulide, to nitrosamine-induced bladder tumors resulted in a dose-dependent reduction in bladder cancer.[19] A comparable study using celecoxib has produced similar results.[20] These data have prompted researchers at the M. D. Anderson Cancer Center to launch a clinical trial using celecoxib for prevention of recurrent bladder cancer.
COX-2 in Cervical Cancer
Finally, the Dannenberg group has evaluated COX-2 expression in cervical cancer and found that among 13 patients studied, 12 expressed significant levels of COX-2, whereas in normal cervical tissue, COX-2 levels remained undetectable. More importantly, COX-2 was found to be overexpressed in cervical intraepithelial neoplasia (CIN), a premalignant lesion. Animal data have yet to be generated to confirm these unpublished results.
Other Oncology Applications
If prostate carcinoma is found to express significant levels of COX-2, then medically manipulated inhibition may afford a viable alternative to some patients who would otherwise be untreatable. Hepatocellular carcinoma is currently known to overexpress COX-2, and, interestingly, COX-2 is also overexpressed in the majority of chronic hepatitis cases. Perhaps COX-2 inhibition plays a role in the progression from chronic hepatitis to hepatic cancer.
Non-small cell lung cancer has also been a target of COX-2 investigation. Among approximately 40 patients, Dr. Dannenberg and colleagues were able to detect COX-2 overexpression in about 90%, regardless of whether the histologic diagnosis was squamous cell or adenocarcinoma. This observation has been confirmed independently by other research laboratories. To test the clinical implications of these findings, a lung carcinoma clone was injected into the paws of mice in a multi-institutional collaborative effort. Different selective and nonselective COX-2 inhibitors, including SC236, celecoxib, and indomethacin were administered and compared. The animal models were then analyzed to determine whether a selective or nonselective COX-2 inhibitor would be useful in preventing or decreasing the growth rate of the tumor, and whether either would be able to prevent metastasis.
In this unpublished study, it was found that both the selective and the nonselective COX inhibitors were able to inhibit tumor growth to approximately the same degree as COX-2 inhibition in colorectal cancer. Responses were seen whether the COX inhibitor was administered before implantation of malignant cells, immediately after implantation, or long after significant tumor growth had occurred. It is currently being investigated whether these responses are due to inhibition of angiogenesis. Metastases were assessed by both number and size, and subjects treated with celecoxib showed reductions in both.
Dr. Dannenberg speculated that selective COX-2 inhibition would likely be used in combination with traditional nonsmall cell lung cancer chemotherapy and that these agents have the potential to augment the antitumor activity of radiotherapy, as has been shown in 2 recently published studies using animal models.[21,22]
COX-2 Inhibitors and Supportive Care
COX-2 inhibitors were originally approved by the FDA, because of their anti-inflammatory and analgesic properties. Independent of their anticancer effects, these drugs have found a place in the treatment of cancer pain. This is consistent since local tissue injury, whether cancer-induced or not, is associated with increased prostaglandin production. In addition, prostaglandin overexpression sensitizes pain receptors to respond to lower levels of prostaglandin stimulation. COX-2 can also be induced in the central nervous system, which has led to speculation that it may be involved in a more centrally mediated type of pain.
Recently, Dr. Dannenberg and colleagues have demonstrated that paclitaxel can activate the COX-2 gene in human mammary epithelial cells. A well-known side effect of paclitaxel is muscle and joint aches, which, for a substantial number of patients, are dose limiting. It is hypothesized that paclitaxel-induced pain may be secondary to COX-2 upregulation of pro-inflammatory prostaglandins. If this is true, then COX-2 inhibition might afford a safer and more effective way of dealing with this complication, thereby allowing for increased use of this highly active chemotherapeutic agent.
Conclusions
As more is discovered about COX-2 activity, more applications to clinical oncology can be anticipated. COX-2 inhibitors will most certainly play a larger role in the prevention and treatment of colorectal malignancies, especially the familial syndromes. And as Dr. Dannenberg has described, COX-2 appears to be present in a host of other tumor types not previously suspected. Clearly, clinical trials will be needed to sort out the significance of COX-2 activity in each of these areas and eventually lead to more effective prevention and treatment strategies. Finally, we should remember that the original purpose of COX-2 inhibition in the management of pain and inflammatory states is also applicable to the management and control of cancer pain, affording physicians a safer alternative to traditional NSAIDs and possibly delaying the need of narcotic agents.
Parkinson's Cure May Be Near
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Updated 4:25 PM ET February 16, 2001
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By PAUL RECER, AP Science Writer
SAN FRANCISCO (AP) - Scientists may be on the brink of curing Parkinson's disease using transplanted embryonic stem cells, but where and when that new treatment is tested in humans depends on unresolved political decisions, researchers suggested Friday.
Dr. Ole Isacson of Harvard Medical School and Dr. Ronald McKay of the National Institutes of Health said Friday they have both "cured" Parkinson's in mice and rats, using stem cells removed from embryos of laboratory animals.
In a report at the national meeting of the American Association for the Advancement of Science, Isacson said mouse and rat embryonic cells, after careful processing, can be grafted into the animal brains where they transform into replacements for cells killed by Parkinson's.
"In mouse models (laboratory tests) these cells have restored function," said Isacson.
Using a slightly different technique, McKay said his NIH lab has also prompted mouse embryonic stem cells to convert into cells that are lacking in Parkinson's.
McKay and Isacson said researchers are almost ready to test the technique in humans, but social and political issues must be resolved in the United States before that step can be taken in this country.
At the same time, McKay said it may happen soon in Britain, France or the Netherlands, as those countries are adopting policies to advance embryonic stem cell research.
"It's going to happen, but just where may depend on social and political issues," McKay said. "There is a great sense of optimism shared by many people in the field right now."
In the United States, some groups, including some members of Congress, oppose the use of embryonic stem cells in research because gathering the cells requires the death of a human embryo.
New NIH guidelines permit federal funding of such stem cell research, but only if the cells are extracted from embryos in labs not receiving federal funding.
Tommy Thompson, the new secretary of Health and Human Services that oversees NIH, said he is reviewing the policy on embryonic stem cells research.
Some researchers have sought NIH funds to conduct embryonic stem cell studies, but no grants have been issued, said McKay.
More than 1 million Americans have been diagnosed with Parkinson's, a disease caused by the death of brain cells that produce dopamine, a key nerve chemical. When patients lose about 80 percent of these cells, they develop the classic Parkinson's symptoms: tremors and rigidity.
Parkinson's can be treated with L-dopa, a drug that makes dopamine in the brain. But L-dopa is effective for only a short time and after that the disease progresses.
Limited experiments using brain cells from aborted fetuses have stabilized patients for up to 12 years, Isacson said. The transplanted cells convert to dopamine-producing cells, replacing those lacking in patients with Parkinson's.
But using tissue from aborted fetuses in research also is opposed by many groups. And because of limited availability and for technical reasons, fetal tissue is not considered ideal for treating Parkinson's.
The best hope, said the researchers, are the embryonic stem cells. These are master cells that can be coaxed to transform into virtually any type of tissue in the body.
Embryonic stem cells can be grown in great numbers, making them readily available for treating thousands of patients, the researchers said.
"You can generate embryonic stem cells with huge
efficiencies," said McKay.
McKay said his lab has found ways to cause mouse embryonic stem cells to change into the dopamine-producing cells lacking in Parkinson's.
"We can take the embryonic stem cells through a series of transitions until they become the dopamine cells," said McKay.
Isacson said his lab injects into the brain specific cells extracted from the embryo and that a natural process in the brain then transforms them into dopamine producers.
"The cells organize themselves to become very functional," he said. "We see the cells behaving in a way to reverse the symptoms (of Parkinson's) in the mouse and rat."
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On the Net:
NIH stem cells: http://www.nih.gov/news/stemcell/index.htm
Parkinson's Disease Association: www.apdaparkinson.org
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Homocysteine May Trigger Strokes
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Updated 2:13 PM ET February 15, 2001
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By DANIEL Q. HANEY, AP Medical Editor
FORT LAUDERDALE, Fla. (AP) - Evidence is building that high levels of the amino acid homocysteine, long implicated in heart attacks, also increase the risk of strokes.
The possible link between homocysteine and strokes is controversial, in part because no one knows for sure whether the substance actually causes them or whether lowering it protects against strokes.
However, several studies released Thursday at a meeting of the American Stroke Association in Fort Lauderdale build the circumstantial case that homocysteine is indeed a factor underlying strokes, the leading cause of permanent disability.
Genes and living habits can make homocysteine levels rise in the bloodstream. "We need to identify whether it definitely is a risk factor or not, how big it is, can we modify it and do we decrease the risk of stroke," said Dr. Ralph Sacco of Columbia University.
One way to lower homocysteine is to increase doses of the B vitamins - folic acid and vitamins B-6 and B-12. A major study under way called VISP - Vitamin Intervention for Stroke Prevention - is testing whether extra doses of these vitamins ward off new strokes in those who have already suffered them.
Evidence of homocysteine's importance comes from a new analysis by Dr. Peter J. Kelly of Massachusetts General Hospital in Boston. His team combined the results of 14 studies involving more than 11,000 patients.
Together, they suggest that people with high levels of homocysteine have a 75 percent higher risk of stroke than do those with average levels. The chance this was a statistical fluke was less than one in 10,000.
The analysis also showed that people who suffer strokes have average homocysteine levels that are 18 percent higher than those who do not.
Dr. Edwould J. von Dijk of Erasmus Medical Center in the Netherlands looked for evidence of small, symptom-free strokes in the brains of 1,077 elderly people. It found that these were twice as common in those with high homocysteine levels.
A study by Dr. Souvik Sen of the New Jersey Neuroscience Institute of Edison, N.J., suggests one way that high homocysteine levels might be bad. Buildups of fatty deposits in the aorta, the main artery leaving the heart, can trigger strokes if globs break off and drift to the brain.
Sen studied 78 victims of strokes and mini-strokes. He found that those in whom this buildup worsened were more likely to have high homocysteine levels.
However, some of these studies might be complicated by the fact that a stroke itself can increase homocysteine levels. Virginia J. Howard, an epidemiologist from the University of Alabama at Birmingham, analyzed preliminary data from VISP and found that homocysteine levels go up about 20 percent during the two weeks following a stroke.
"This raises questions about cause and effect," she said. "Which came first?"
Genes can raise homocysteine levels, as can B vitamin deficiency, kidney disease, aging and possibly alcohol abuse and lack of exercise, among other things.
To help protect against birth defects, the Food and Drug Administration ordered manufacturers to begin fortifying flour, rice and other grain foods with folic acid in 1998. This appears to be having the added benefit of lowering homocysteine levels.
A study last year of white, middle-aged residents of Framingham, Mass., found that average blood levels of folic acid doubled and average homocysteine levels fell about 7 percent after the change in food.
While grain foods, such as breakfast cereal, have become a primary source of folic acid, vitamin B-6 comes mostly from fruits and vegetables and vitamin B-12 from red meat. All of these are also found in multivitamins.
No one knows precisely what the ideal homocysteine level is. However, doctors estimate that one-quarter of the U.S. population has clearly elevated levels.
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Antitumor Immune Response Induced by Cancer Vaccine
February 5, 2001 Clinical Cancer Research/MedscapeWire
According to the results of a clinical trial, a mixed ganglioside conjugate vaccine (MGV, Progenics Pharmaceuticals, Inc.) can induce antibodies against 2 different targets on cancer cells. Cancer patients from New York's Memorial Sloan-Kettering Cancer Center were treated with the new vaccine, which was also found to be free of significant toxicity. The trial results are published in the December issue of Clinical Cancer Research.
The vaccine is designed to stimulate a patient's immune system to control or eradicate residual cancer cells after surgery, radiation, or chemotherapy without damaging healthy tissue, by stimulating the formation of antibodies to GM2 and GD2 gangliosides. These cancer antigens are present in many of the most common types of cancer, including colorectal and gastric cancers, small cell lung cancer, lymphoma, sarcoma, and neuroblastoma. The vaccine contains the GM2 and GD2 antigens separately coupled to the carrier protein keyhole limpet hemocyanin (KLH) and mixed with QS-21 adjuvant (an immune system stimulant).
The study evaluated 31 patients with malignant melanoma or sarcoma. The vaccine induced antibodies to the GM2 ganglioside in 97% of patients. In addition, 91% of patients who received an optimal dose of the vaccine also developed antibodies to GD2. Progenics previously reported that anti-ganglioside antibodies taken from vaccinated patients kill tumor cells in vitro.
"We have demonstrated for the first time in patients that it is possible to induce antibody responses to two gangliosides using a bivalent vaccine," said Paul B. Chapman, MD, associate attending physician at Memorial Sloan-Kettering Cancer Center and the lead author of the report. "This two-pronged attack may significantly enhance the efficacy of the vaccine against a variety of important cancers."
Clin Cancer Res. 2000;6:4658-4662
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Nobelist Predicts Marriage of Psychiatry, Neurology
WESTPORT, CT (Reuters Health) Feb 06 - Psychiatry is in crisis, but molecular genetics and imaging are pushing this beleaguered discipline closer to neurology and will eventually resolve this crisis, a Nobel laureate predicts.
"Neurology and psychiatry are really one, and should be treated that way," Dr. Eric R. Kandel said at a media briefing on Tuesday introducing the February 7th issue of The Journal of the American Medical Association.
The issue, a collaboration between JAMA and the Albert and Mary Lasker Foundation, focuses on medical research in the 21st century — and marks the first time that the journal has collaborated with another institution.
Dr. Kandel, who won the 2000 Nobel Prize for Physiology or Medicine for his work on signal transduction in the nervous system, is founding director of the Center for Neurobiology and Behavior at Columbia University, a university professor at Columbia and a senior investigator at the Howard Hughes Medical Institute.
He co-authored an article on neurology and psychiatry, one of 13 in this week's JAMA addressing the future of specific diseases and disorders. Nine other articles cover research opportunities in particular fields, such as biomedical engineering, genomics and gene and stem cell therapies.
When he trained in psychiatry at Harvard in 1960, Dr. Kandel said at the briefing, "the best and the brightest" considered entering the field. Gradual understanding that psychoanalysis would not cure all forms of mental illness, and more recently pressure from HMOs, have made psychiatry a much less attractive option today, he added.
"Psychiatry needs a new intellectual framework, it needs a new way of training," said Dr. Kandel, adding that molecular genetics and imaging are beginning to provide this framework.
For example, he noted, imaging has begun to make it possible to identify the nerve pathology for various types of mental illness. In patients with schizophrenia, enlarged ventricles and shrinkage of parts of the prefrontal cortex have been observed, as well as reduced metabolism in the prefrontal cortex.
In addition, Dr. Kandel said, new research using PET scans suggests that psychotherapy works as well as medication for correcting abnormalities of the basal ganglia found in obsessive-compulsive disorder. "Imaging techniques may become sensitive enough to pick up the effectiveness of psychotherapeutic intervention," he added.
Dr. Kandel pointed to dramatic advances in the understanding of Huntington's disease, as well as steps toward prevention and treatment of this condition, as a model for investigating disorders caused by a mix of genetic and environmental factors, such as obsessive-compulsive disorder, schizophrenia and depression.
This investigation will require closer cooperation between neurology and psychiatry, Dr. Kandel writes in the JAMA article he co-authored with Dr. W. Maxwell Cowan of the Howard Hughes Medical Institute in Chevy Chase, Maryland.
"To function effectively, psychiatrists of the future will need more than just a nodding familiarity with genetics, imaging, and neuroscience. The knowledge they will need may be different from that of a well-trained neurologist, but fully comparable in the level of expertise," Drs. Kandel and Cowan write.
Growing collaboration between psychiatry and neurology will be most beneficial, the authors continue, for patients who are currently treated by both psychiatrists and neurologists, including those with "autism, mental retardation, and the cognitive disorders associated with Alzheimer and Parkinson diseases."
JAMA 2001;285:601-605.
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TAMOXIFEN AND BREAST CANCER-- THIS IS PART OF AN INTERESTING ARTICLE I HAVE EXCERPTED ON THIS TOPIC
ENDOMETRIAL CANCER IN A WOMAN ON LONG TERM TAMOXIFEN THERAPY
by Satish R Rao*, Raja S Rao**
INTRODUCTION Tamoxifen is a non-steroidal substance which is widely used in the treatment of breast cancer. Worldwide, about seven million women are taking tamoxifen. [1] It is a safe drug with no side effects. However it has the potential to induce endometrial carcinoma. The incidence of endometrial carcinoma in women, who are on tamoxifen, is estimated to be 1.4/1000 women as compared to .7/1000 in the general population. [2]
DISCUSSION Tamoxifen is an oestrogen antagonist at some sites and estrogen agonists at other sites. It is anti-estrogenic in the breast. It does not cause any osteoporosis or alteration in lipid metabolism. It causes proliferation of the endometrium. Women on long term tamoxifen therapy are at risk of developing endometrial cancer. This has been a cause for widespread concern.
One thing that comes out consistently in all the trials is the immense benefit, women derive from tamoxifen. In a meta analysis of 29892 cases, there was 17% decrease in overall mortality and 39% decrease in the incidence of cancer in the contralateral breast. [11] The benefits were seen in all subsets, premenopausal, post menopausal, node +ve, node -ve, ER+ve and ER-ve. The benefits were more marked in post menopausal, ER+ve group. These results have stimulated further trials of tamoxifen as a chemo preventive agent in women deemed to be at high risk for breast cancer.
The current recommendation is that women on chronic tamoxifen therapy should undergo an annual clinical gynecological checkup. Ultrasound examination gives an indication of the thickness of the endometrium. However it should be interpreted cautiously. [12] Should a woman be symptomatic, e.g. postmenopausal bleeding, further investigation like curettage must be done. If indicated, a pan hysterectomy should be done.
Efforts are on to find new drugs which have no action on the endometrium. Raloxifen [13] is one such drug which prevents osteoporosis and which has no agonist action on the endometrium. However its role in treatment of carcinoma breast is yet to be defined.
CONCLUSION The benefits of tamoxifen for patients with breast cancer far outweigh its side effects. Women on tamoxifen therapy should have annual gynecological checkup. Efforts are on to synthesize a drug which is anti-estrogenic in breast tissues and has no agonistic action on the endometrium.
POSSIBLE ALZHEIMER VACCINE FOUND
Updated 2:00 PM ET December 20, 2000
By MALCOLM RITTER, AP Science Writer
Taking what could be an important step toward preventing Alzheimer's, scientists found
that an experimental vaccine can largely ward off memory loss in mice stricken with a
similar disease. The vaccine is already being tested in people.
"This potentially could be a major breakthrough for us," said Zaven Khachaturian, senior science adviser to the
Alzheimer's Association.
But he stressed that treatments that work in mice do not necessarily help people and that the mouse research did not
deal with some key mental abilities lost in Alzheimer's, such as language and judgment.
The vaccine made headlines last year when scientists reported that it largely blocks the formation of protein deposits
called amyloid plaques in the brains of mice. Such plaques are a hallmark of Alzheimer's.
But the next step was to find whether the vaccine makes any difference in the animals' mental functioning.
Two studies published in Thursday's issue of the journal Nature found that the vaccine does indeed make a difference.
The research was conducted by two independent research teams, centered at the University of South Florida in Tampa and the University of Toronto in Ontario, Canada.
The studies used strains of mice that develop lots of amyloid plaques in their brains, along with measurable memory deficits, because of the genes they carry.
The researchers used different versions of a procedure in which mice swam until they learned the location of an underwater platform. The animals were then tested to see how well they remembered where the platform was. Alzheimer's patients frequently have trouble remembering locations and how to get to destinations.
Both studies found that mice that had been repeatedly vaccinated performed markedly better than the untreated plaque-forming mice in the memory tests. On some occasions they did as well or nearly as well as ordinary mice.
University of South Florida researcher Dave Morgan said his vaccinated mice were slower to learn the platform location but eventually remembered it as well as ordinary mice did.
This past July, drug company scientists announced that preliminary results in human patients indicated the vaccine was safe. Those tests were not designed to assess any effect on symptoms.
Human tests are continuing under the sponsorship of Elan Corp. of Dublin, Ireland, and American Home Products
Corp. of Madison, N.J. Neither company paid for the new mouse studies.
The researchers who carried out the mouse studies said it is not clear why the vaccine protects memory. For one
thing, the research does not settle the question of whether the plaques actually cause the symptoms of Alzheimer's.
The vaccine was designed to make the mouse immune system attack amyloid-beta peptide, also called beta amyloid,
a key component of the brain plaques in Alzheimer's. And both studies found that vaccinated mice had fewer and smaller amyloid plaques in their brains. But Morgan noted that his treated mice still had a lot of plaques.
He and Dr. Peter St George-Hyslop, one of the University of Toronto researchers, suggested the vaccine might act on a harmful form of amyloid-beta peptide outside of the plaques.
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Celiac Disease Overlooked as Cause of Iron-Deficiency Anemia
WESTPORT, CT (Reuters Health) Feb 05 - Especially in menstruating women, celiac disease appears to be underinvestigated as a potential cause of iron-deficiency anemia, according to data published in the current issue of the British Journal of Haematology, dated December.
Dr. D. J. Unsworth of Southmead Hospital in Bristol, UK, and colleagues identified 483 blood samples from prospective blood donors who met study criteria for anemia (hemoglobin <11 g/dL for women, <13.5 g/dL for men in order to recruit enough men). Of the donors, 28 women (26 premenopausal) and 4 men tested positive for IgA anti-endomysial antibodies and were asked to undergo further followup for celiac disease.
Of the 25 subjects who underwent endoscopic small intestinal biopsy, 22 "had histological changes compatible with celiac disease," the researchers write. Twenty-one of these were women, and Dr. Unsworth's team notes that none of the women had been previously investigated for the possibility of celiac disease.
The research team reports that their screening of anemic adults for celiac disease resulted in a detection rate of over 6%, compared with 0% detection of celiac disease using EDTA blood samples from 250 nonanemic blood donors.
"Celiac disease serology is easy, cheap and reliable," the authors write. "We recommend that all cases of anemia of uncertain cause, including all women with anemia ascribed to menstrual blood loss or poor diet, be checked for celiac disease-associated autoantibodies."
Br J Haematol 2000;111:898-901.
Arthritis Cure ?? Updated 10:15 AM ET October 30, 2000
LONDON (Reuters) - British scientists have announced what they say is the first
evidence of a cure for rheumatoid arthritis, the Sunday Telegraph newspaper reported
Sunday.
A research team at University College in London says it has discovered what causes the
body's defenses mistakenly to attack healthy joints and tissue. Its cure focuses on the
role of B-cells, white blood cells that defend the body against viruses and bacteria by
making antibodies that attack the hostile microbes.
B-cells can accidentally make antibodies that attack healthy tissue. The University
College team told the Sunday Telegraph that in the case of arthritis, the result is a
self-sustaining attack on joints and tissue.
"It probably takes just one genetic mistake in a lifetime to trigger this reaction but once it
gets going it becomes a vicious circle," said Professor Jonathan Edwards, who is leading
the team. The team said it had found a way to break the circle, using drugs that seek out
and destroy B-cells.
"Unlike with other cells in the immune system, most people can live without any B-cells for
a while," Edwards said. "By the time we reach adulthood we have already made most of
the antibodies we need."
The body responds to the destruction of all its B-cells by making fresh ones. The chances
are small that these new B-cells will make the same mistake as their predecessors and
trigger a return of rheumatoid arthritis.
Of 20 patients who underwent 18 months of treatment, five now have only some residual
pain from the damage already done.
"They have returned to leading a more or less normal life, with one going to the gym and
one taking up gardening for the first time in ages. So far, of the total of 20 patients only
two have had no benefit at all," Edwards said.
The patients have had rheumatoid arthritis for an average of 20 years, he added.
Edwards said the B-cell based therapy might also offer hope to patients with other
auto-immune diseases, such as Crohn's disease, lupus and even multiple sclerosis.
The team will announce the results of its research Monday at the annual scientific
meeting of the American College of Rheumatology in Philadelphia. The findings will be
also published in the leading journal Rheumatology.
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New ADHD Drug Promising in Early Studies
NEW YORK (Reuters Health) - A new drug being developed as a treatment for attention deficit hyperactivity disorder (ADHD) in children may be an alternative to Ritalin, according to results presented at a meeting Thursday.
In two trials, a total of 291 children with ADHD, between 7 to 13 years of age, received 9 weeks of treatment with either Ritalin, the new drug, called tomoxetine, or an inactive placebo. The results were presented at the American Academy of Child and Adolescent Psychiatry annual meeting here.
Although tomoxetine fell just short of being as effective as Ritalin, the drug did reduce symptoms in most children, according to Eli Lilly, the company developing the drug.
Unlike Ritalin or Dexedrine, tomoxetine, is not considered a stimulant.
``Tomoxetine is a very exciting option that could help people for whom stimulants don't help or they're not used for other reasons,'' Dr. Thomas Spencer of Massachusetts General Hospital, a scientist involved with the trials, told Reuters Health.
``About 30% of kids don't respond to Ritalin but tomoxetine has a completely different mechanism.''
Eli Lilly researcher Dr. John Heiligenstein, speaking at the meeting, added that ``there is a clear advantage for non-stimulant drugs that come to the market.''
In addition, Dr. Spencer said, tomoxetine ``is very selective and has very few side effects.'' Due to their potential for abuse,
Ritalin and Dexedrine are classified as controlled substances. Adverse effects can include loss of appetite, anxiety, Hallucinations, changes in mood and insomnia.
In contrast, Lilly maintains that the only side effect associated with tomoxetine in the trials was loss of appetite. Tomoxetine also had less of an effect on sleep than Ritalin, the company noted.
The company is undertaking a larger study with 1,000 to 1,500 patients, Dr. Spencer noted.
The company anticipates completing that study early next year, a Lilly spokesperson told Reuters Health. Assuming a quick filing of a new drug application with the US Food and Drug Administration (FDA), tomoxetine could, if approved, be on the market as early as 2002.
``There is general agreement that it would be wonderful to have an alternative to the stimulants,'' Dr. Spencer said. Two other companies, Glaxo Wellcome and Abbott Laboratories, are also developing non-stimulant treatments for ADHD.
Results of a study of Glaxo's experimental drug GW320659 were presented at the same meeting this week. The results showed that the drug was ``well tolerated and may be effective in treating ADHD in children,'' Glaxo spokesperson Holly
Russell told Reuters Health.
Glaxo's drug is slightly different from tomoxetine, but it is still considered a non-stimulant, Russell said. She added that the company is not strictly focusing on ADHD but instead plans to develop GW320659 ``quite broadly in a range of therapeutic areas.''
Abbott Laboratories is developing another drug, called ABT089, which ``is very different than Ritalin,'' a company spokesperson told Reuters Health. ABT089 ``acts on different receptors in the brain (than Ritalin),'' the spokesperson said.
ABT089 is still in laboratory studies and it remains uncertain when trials in humans may be launched, she said.
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Ovarian Cancer Drug Approved
By Laura Gilcrest
WASHINGTON (Reuters Health) - Alza Corporation has received approval in the Europe Union (EU) to market its anti-cancer drug Caelyx (pegylated liposomal doxorubicin) for treating advanced ovarian cancer in women who have failed other therapy.
About 20% of patients with the disease do not respond to chemotherapy and approximately 50% who do respond experience relapse within 2 years.
Caelyx, called Doxil in the US, uses a targeted delivery system called Stealth, which helps the drug evade detection by the body's immune system for a longer period, increasing the likelihood that the medication will reach the targeted tumor, according to the company.
Approximately 25,200 new cases of ovarian cancer were diagnosed in the US in 1999 compared with about 35,000 cases in the EU. Ovarian cancer, the second most common gynecological cancer in the US and the deadliest, is often diagnosed in
an advanced stage, because it presents few early symptoms,
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ECZEMA NEW THERAPY
WASHINGTON (AP) - The first new type of drug in decades to treat the troubling skin
disease eczema won government approval Friday: an ointment named Protopic that can
ease the often severe itching of both adults and children.
The Food and Drug Administration cautioned that Protopic shouldn't be the first therapy
for all patients, but reserved for those with moderate to severe eczema who aren't
adequately helped by other treatments or can't tolerate them.
The manufacturer, Japan's Fugisawa Healthcare, plans to begin shipping the prescription
cream in February, but refused to disclose the price.
Eczema is a skin inflammation that causes itching and oozing lesions that recur often,
sometimes starting in infancy and plaguing patients throughout their lives. Just what
causes it is unknown, although people with allergic disorders seem at higher risk.
There is no cure, but corticosteroid creams, antihistamines and, as a last resort for
severe cases, steroid-containing pills are common treatments. Doctors caution that
steroid medications, even cream versions, can cause some serious side effects and
must be used very carefully. So patients have long hoped for new alternatives.
Protopic is the first topical immune-suppressing drug, a cream version of an
immune-system inhibitor called tacrolimus that, in oral and intravenous versions, already
is used to help prevent rejection in organ transplant recipients.
The theory is that the cream version helps eczema by inhibiting immune-system cells
called T cells that may be overactive in the skin inflammation.
In clinical studies, between 28 percent and 37 percent of patients who used Protopic daily
for three months found it cleared up most of their eczema outbreak, compared with only 7
percent who had success with a dummy cream.
It was not a cure: Once people quit using the cream, eczema gradually returned. So far,
the FDA can say only that using it for a year is safe; Fugisawa agreed to conduct
longer-term safety studies.
"It is important to have this alternative because there are patients who suffer" serious
problems from standard eczema therapies, said FDA medical officer Dr. Martin Okun.
But Protopic isn't risk-free, he warned: -Users should stay out of the sun. Because Protopic affects the immune system, some scientists worry that it might mix with sun exposure to increase the risk of skin cancer. The possibility remains under study.
-Don't use Protopic until skin infections are healed. The drug may increase risk of certain
skin infections, including a serious herpes virus-caused infection called eczema herpeticum.
-Most common side effects were skin burning or tingling in up to 60 percent of patients.
But after a month of use, less than 10 percent report that continues to be a problem.
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2: Recent Results Cancer Res 2001;158:204-7
Decrease in circulating tumor cells as an early marker of therapy effectiveness.
Bystryn JC, Albrecht J, Reynolds SR, Rivas MC, Oratz R, Shapiro RL, Roses DF,
Harris MN, Conrad A
Kaplan Comprehensive Cancer Center, NYU School of Medicine, NY, USA.
[Medline record in process]
As melanoma cells are present in the circulation of many patients with this
cancer, decreases in their number could provide an early indication of therapy
effectiveness. To evaluate this possibility, we examined the effect of treatment
with a melanoma vaccine on the number of melanoma cells present in the
circulation. PCR was used to detect melanoma cells that expressed the
melanoma-associated antigens MART-1, MAGE-3, tyrosinase and/or gp100 in 91
patients with melanoma. Melanoma cells that expressed one or more of these
markers were present more often in advanced disease, i.e. in 80% of patients
with advanced stage IV compared to in less than one-third of patients with less
advanced disease. We then measured circulating melanoma cells in a subset of 43
of these patients who were treated with a polyvalent, shed antigen, melanoma
vaccine. The vaccine contains multiple melanoma-associated antigens including
MART-1, MAGE-3, tyrosinase and gp100. Immunizations were given intradermally
q2-3 weeks x4 and then monthly x3. Prior to vaccine treatment, circulating
melanoma cells were detected in 14 (32%) patients. Following 4 and 7 months of
vaccine treatment, melanoma cells that expressed any of these markers were
present in only nine (21%) and three (7%) of patients, respectively. Thus,
vaccine therapy was associated with clearance of melanoma cells from the
circulation in 78% of initially positive patients. As the number of these cells
declined steadily with increasing length of therapy, it is unlikely that this
was due to a random change in their number. Rather it suggests that the decline
was a result of the therapy. These observations suggest that the presence of
melanoma cells in the circulation is related to the extent of the melanoma, and
that their disappearance may provide an early marker of the efficacy of therapy.
However, the practical utility of assaying circulating tumor cells as a guide to
the effectiveness of therapy or of prognosis will need to be confirmed by
correlations with clinical outcome.
Grant support:
5 R21 CA75317/CA/NCI
1 R21 CA78659/CA/NCI
PMID: 11092048, UI: 20543541
Study: Herpes Virus Helps Kill Skin Cancer Cells
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Updated 12:29 AM ET February 16, 2001
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By Patricia Reaney
LONDON (Reuters) - A common virus that causes cold sores could be a new weapon in the fight against metastatic melanoma, a skin cancer that has spread to other parts of the body, researchers in Scotland said on Friday.
The herpes simplex virus is one of a family of viruses that carry DNA which causes infections. Genital herpes, shingles and chickenpox result from similar viruses.
Doctors are already using the herpes simplex virus to treat patients suffering from glioma, a type of brain cancer. New research by scientists at the University of Glasgow shows that a disabled herpes virus, or one that doesn't cause cold sores, can kill skin cancer cells.
"We have proved that if you bring the virus into direct contact with the (cancerous) cells it appears to kill them," Professor Rona MacKie told Reuters.
"I see this as quite likely to play a part in the management of patients with melanoma in the future. What we have to sort out is what stage in recognition of the development of melanoma is best to start using this," she added in a telephone interview.
VERY EARLY DAYS
MacKie tested the disabled herpes virus on five patients with melanoma, the most deadly form of skin cancer. Their research is reported in The Lancet medical journal. In all of the patients the cancer had spread and they had lumps or secondary tumors that were close to the surface of the skin.
The researchers injected the disabled virus and a harmless saline solution directly into two tumors on each patient to compare the results.
They varied the number of injections and the time period over which they gave them to the patients. When the lumps were removed and examined the scientists discovered that the virus did what they had expected -- it killed melanoma cells.
In patients given more injections the damage to the cancerous cells was greater.
"It is very early days," said MacKie. "The important thing is that it (the virus) has done no harm and, over and above that, we have shown that looking down a microscope it appears to kill melanoma cells."
MacKie said the herpes virus tends to attack two types of cells. One type is derived from the nervous system, which melanomas are, and the other type is cells that are rapidly dividing which is a characteristic of cancer.
Now that the researchers have proven that the treatment is safe they are planning further trials to determine the optimum dose.
Although melanomas account for only about 10 percent of skin cancers they cause up to 85 percent of skin cancer deaths. Cases of the disease have increased more during the past decade than any other cancer, except lung cancer in women.
Sunbathing and too much exposure to the sun's harmful UVA and UVB rays increase the risk of melanoma. Half of the cases of the disease are in people under 50.
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INFLAMMATION PROTEINS MAY HELP PREDICT HEART ATTACK
troponin T and C-reactive protein
NEW YORK (Reuters Health) - Blood proteins that are involved in inflammation could help predict a heart disease patient's risk for having a heart attack or dying due to heart disease, researchers say.
Earlier studies have suggested that certain inflammatory proteins play a key role in atherosclerosis, the accumulation of fatty plaques in arteries that can lead to heart attack. Two new studies show that measuring levels of some of these proteins, in addition to risk factors such as cholesterol, makes predicting cardiac risk more accurate.
Both of the studies appear in the October 19th issue of The New England Journal of Medicine. In the first study, lead author Dr. Bertil Lindahl and colleagues at the University of Uppsala in Sweden report that two proteins, troponin T and C-reactive protein ``are strongly related to the long-term risk of death'' from a heart attack. Troponin T is released by damaged heart muscle and C-reactive protein increases with inflammation.
They conclude that the level of these two proteins can be used to predict the risk for a heart attack and that ``their effects are additive with respect to each other and other clinical risk factors.''
In the second study, Dr. Chris J. Packard, of the Glasgow Royal Infirmary in Scotland, and colleagues looked at an enzyme known as lipoprotein-associated phospholipase A2. They found that the enzyme--independently of other risk factors-could predict heart attack risk in men who had elevated cholesterol levels.
In the study of 580 men with elevated cholesterol and 1160 healthy men, they found that those with the highest blood level of phospholipase-A2 were nearly twice as likely to have a fatal or nonfatal heart attack, or to need surgery or other treatment, compared with men with the lowest levels. Levels of phospholipase A2 are linked to inflammation.
The study was funded by a grant from Bristol-Myers Squibb and diaDexus, a Santa Clara, California-based company that manufactures a test for phospholipase A2. Combining the results of these studies with other known risk factors will help improve doctors' ability to predict heart disease risk, researchers say.
``It is now generally recognized that although the use of traditional risk factors (like elevated cholesterol, high blood pressure and obesity) produces reasonably accurate estimates of risk in populations, this approach allows clinicians to predict only
about 50 to 60 percent of the variation in the...risk of an event in individual patients,'' writes Dr. Daniel J. Rader in commentary accompanying the research articles.
``Therefore, the addition of other factors that would increase the predictive ability would also improve the accuracy of decisions regarding the use of proven preventative therapies.''
SOURCE: The New England Journal of Medicine 2000;343:1139-1155,1148-1155.
Lyme disease?
Lyme disease is caused by the bite of a tick that is infected with a germ. A tick is a small insect-like creature that sucks the blood of mammals. The germ enters the body at the spot where the tick has bitten, and can travel to different parts of the body through the blood. If not treated, Lyme disease can affect joints, the nervous system, the heart and the skin. It can make these areas swell and become painful. This is called inflammation. This inflammation can also cause other problems
Lyme disease is an inflammatory disorder begun by receiving a bite from a tick that is infected by a bacterium. The bacterium enters the body at the spot of the tick bite, and begins to multiply and travel to different parts of the body. If untreated, it can progress to produce an infection that can take a variety of forms, but usually involves chronic inflammation affecting joints, the nervous system, the heart and the skin.
This disease has only been recognized since November 1975 when 12 children of a small rural community, Old Lyme, Connecticut, were diagnosed with juvenile rheumatoid arthritis. Nearby several other people also reported a similar type of arthritis that came on suddenly. Research was done and 51 individuals were found to have developed the same disorder in a small geographical area and at the same time of the year. Most had brief attacks of pain and swelling involving a few large joints, and many reported having noticed a peculiar, expanding, red skin area several weeks beforehand. One recalled being bitten by a tick at the site of the skin lesion. The type of rash was recognized as one that had been known to occur in Europe, where it had been associated with the bite of a sheep tick.
How common is Lyme disease?
The exact number of Canadians affected by Lyme disease is not known. Men and women can affected by Lyme disease. It can affect people at any age, though many cases appear in those between the ages of 11-14 or in young adulthood. People who engage in outdoor activities such as hiking, hunting and climbing may be more at risk of being bitten by ticks, and therefore have a greater chance of getting Lyme disease.
The incidence of Lyme disease seems to have increased over the years, but this may only be due to wider recognition of the symptoms and disease. The exact number of people affected by Lyme disease is not known.
Lyme disease occurs widely in Europe, the Soviet Union, China, Japan and Australia. In North America it is most common in the northeast and north central regions, and so far has been less common on the west coast. While cases have been reported from most states and provinces in North America, the majority of cases occur in just a few. In Canada, the greatest number of confirmed cases (199) have been in Ontario, while there have been no confirmed cases in Newfoundland, Prince Edward Island, Nova Scotia, the Yukon and the Northwest Territories.
Because there are more and more people these days engaging in outdoor activities such as hiking, hunting and climbing this may have caused an increase in the incidence of Lyme disease. These people more frequently encounter deer or are in areas where deer have been. The tick that passes Lyme disease along is called a deer tick. It often lives on and is carried from one area to another by deer.
Cases of Lyme disease have occurred in people of all ages, but the peak incidence is in people between the ages of 11-14 or in young adulthood. Most cases begin in the summer. In areas that have mild winters the pattern is less seasonally specific.
What are the warning signs of Lyme disease?
There are three separate stages of Lyme disease. Each has different symptoms.
first stage a skin rash may appear at the site of a tick bite. The area may feel hot to the touch, but is usually not painful. The rash grows in size over time. The rash may develop anywhere from a few days up to month after the tick bite. 30% of people who develop Lyme disease do not get this rash.
second stage Fatigue, headaches, fever, chills, aching joints and muscles, and skin sores or rashes often appear during the
third stage Lyme disease may spread to affect areas of the body like the heart and the nervous system.
Localized early disease stage
The onset of Lyme disease is called the localized early disease stage. If you have been infected with Lyme disease you may get a skin rash at the site of a tick bite. Common bite locations are the groin, the buttock, behind the knee or in the armpit. The rash may appear anywhere from a few days to a month after the tick has bitten. It may feel hot to the touch and is usually red around the outside with a clear centre. Beginning as a small area, it expands slowly in size over several days. It is usually not painful. Many people do not realize a tick has bitten them, and about one-third of people do not develop this rash.
Secondary stage
Within several days of the appearance of the skin lesion, many people develop symptoms and evidence of more widespread infection. This is called the secondary stage of the disease. In this stage, you could have a vague feeling of discomfort or uneasiness, feel sluggish or fatigued, get headaches, and have fever and chills. You might also have aching joints and muscles, and develop skin sores or rashes on various parts of your body.
Third stage
About 20% of people with Lyme disease have remission after the secondary stage has passed. Most people, however, will move into the third stage of the disease. In this stage you could develop other problems that involve the heart, nervous system and joints. Inflammation of the heart, called carditis, develops in fewer than 10% of people with untreated Lyme disease. Initial symptoms can include rapid beating of the heart (palpitations) or unexplained fainting. This condition may pass on its own, but it sometimes requires medical intervention.
If your nervous system becomes inflamed you could early on in the disease experience headaches, irritability, sensitivity to bright light and lethargy. In about 15% of people, meningitis (characterized by headache and the classic neck stiffness) may occur a few weeks after the initial rash.
Other symptoms indicating involvement of the disease in the brain and the nerves may occur months to years after the disease onset. Nerves in the limbs or around the head may be affected, and you could experience muscle weakness, paralysis or loss of sensation. Bell's palsy, a condition that results in weakness or paralysis of the facial muscles, can occur. If the disease affects your brain, you may experience short-term memory loss, have difficulty concentrating, and suffer from chronic fatigue, headaches and sleep disturbance. In rare cases the disease can cause seizures and lesions on the spinal cord.
Pain in the muscles and joints is common early on in Lyme disease. Many people experience spontaneous improvement of the pain, or a diminishment of it over time. In about 20% of people with untreated Lyme disease, this inflammation - or arthritis - of the joints can become chronic.
Most people with advanced Lyme disease experience attacks of arthritis involving one or only a few joints. Usually it is the large joints, such as the knees, that are affected. Involvement of many joints is uncommon. Attacks can last a few days to a few weeks. In children the arthritis is usually much milder. Despite the ongoing inflammation, it is unusual for it to result in damage to the cartilage and bone, as may occur more commonly in other forms of arthritis.
What causes Lyme disease?
A germ that is carried by a tick causes Lyme disease. This germ is a bacterium that is transferred when a tick bites through the skin. The cause of Lyme disease is a spiral-shaped bacterium (spirochete) called Borrelia burgdorferi. A tick can carry this bacterium in its body, and transfer it to its host when biting through the skin. The type of tick that carries this bacterium most often bites and sucks the blood of deer, and so is called a deer tick, but it will also bite humans and any other mammals.
What can you do about Lyme disease?
If your doctor thinks you have Lyme disease, he or she may perform a physical examination, and order laboratory tests. Your doctor may look for evidence of a rash or ask if you have had a rash or remember being bitten by a tick. Most of the time, Lyme disease can be cured, especially if it is treated early. he goal of treatment is to control inflammation and kill the bacteria that have caused the disease. Learn as much as you can about this disease.
Most of the time Lyme disease can be cured if it is treated promptly and properly. However, without treatment the disease can continue to progress and affect more parts of the body.
Establishing the correct diagnosis is important, so if your doctor thinks you have Lyme disease, he or she may ask questions about your symptoms, other medical conditions, recent travel, illnesses, and contact with people who may have had infections.He or she may perform a physical examination, and look for evidence of a rash. X-rays and other tests might be ordered to find out whether the infection and inflammation is being caused by a germ.
It is often difficult to diagnose Lyme disease because of the variation in symptoms and the course of the disease. There is also no routine definitive test to determine if Lyme disease is the cause of illness.
The main objective in the treatment of Lyme disease is to control the pain and inflammation and to eradicate the infection. Your active involvement in developing your treatment plan is essential.
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Obese Kids, Heart Disease Link Found
Updated 12:57 AM ET January 9, 2001
By LINDSEY TANNER, AP Medical Writer
CHICAGO (AP) - Overweight children as young as 8 have been found to have a
smoldering type of bloodstream inflammation that in adults has been linked to heart
disease.
The new study may help explain why people who were overweight as children run a
higher risk of cardiovascular problems and diabetes in adulthood, regardless of their
adult weight.
The study, published in the January issue of the journal Pediatrics, is the first to link
childhood weight and inflammation. The research was led by Marjolein Visser, an
epidemiologist from Vrije University in Amsterdam.
The researchers looked at 3,561 U.S. children ages 8 to 16 and found that overweight
youngsters were three to five times more likely than those of normal weight to have
inflammation, as marked by the presence of a substance called C-reactive protein, or
CRP, in the bloodstream.
Dr. Michael Steelman, past president of the American Society of Bariatric Physicians, a
group of doctors specializing in obesity, said the finding is a major reason for concern.
"When we can start documenting the physical changes occurring at that age, it's just like
a time bomb just below the surface of their skin that's going to go off someday,"
Steelman said.
The study does not address whether inflammation in children poses any short- or
long-term risks. But Visser said previous research has linked elevated CRP levels in
overweight adults with the development of heart problems.
In Visser's study, 7 percent of the boys and 6 percent of the girls showed signs of CRP
inflammation. Elevated white blood cell counts, another sign of inflammation, were also
far more common in overweight children.
Previous research has suggested that elevated CRP levels may stem from artery
inflammation during the early stages of heart disease. The body may respond to plaque
buildup the same way it responds to infection - by releasing disease-fighting cells that
cause inflammation.
Aspirin, because of its blood-thinning properties, is sometimes recommended for adults
at increased risk of heart disease. But because aspirin is also known to reduce
inflammation, some experts have suggested this benefit may be the real reason it helps
reduce the risk.
Visser said the findings are too preliminary to recommend aspirin for overweight
children with elevated CRP levels.
"If the relationship between obesity and elevated CRP levels is causal, weight loss would
be the recommended treatment for overweight children," said Visser, who worked with
the U.S. National Institute on Aging on the study.
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Diuretics Help Stop Strokes
Updated 4:00 PM ET January 7, 2001
By LINDSEY TANNER, Associated Press Writer
CHICAGO (AP) - Treating high blood pressure with drugs works best at preventing one
of its major complications - strokes - if common pills called diuretics are included, new
research suggests.
The study involved 3,170 patients taking one or more drugs to treat high blood
pressure, the single most important cause of strokes.
Among those without underlying heart disease, treatment without a diuretic was linked to
an 85 percent increased risk of stroke, compared with therapy including a diuretic.
Diuretics are among the oldest drugs used to control high blood pressure, which the
American Heart Association estimates afflicts as many as 50 million Americans,
including one in four adults.
When choosing to control high blood pressure with drugs, many doctors recommend
beginning with diuretics, sometimes called water pills, which work by flushing excess
sodium and water from the body.
Other treatments include beta blockers and more expensive medication such as
calcium antagonists and ACE inhibitors. Some patients require more than one type of
drug to keep blood pressure under control.
The current study, reported in Monday's Archives of Internal Medicine, compared
stroke risk in patients taking one or more of these drugs. Results were based on
medical records and telephone interviews with patients aged 30 to 79, including 380
who had suffered a stroke.
Even among users of two blood pressure drugs, those who didn't use a diuretic faced a
40 percent greater stroke risk than those who used the pills, according to researchers
from the University of Washington and Utrecht Institute of Pharmaceutical Sciences in
the Netherlands.
The link was much less pronounced in patients with underlying heart disease.
Investigator Olaf Klungel and colleagues theorized that diuretics may be more effective
than other drugs in lowering systolic blood pressure, the top number on a reading,
reflecting pressure when the heart contracts. Research has suggested that a high
systolic reading may be most strongly associated with stroke risk.
George Hademenos, staff scientist at the American Stroke Association, which was not
involved in the research, said the findings are too preliminary to make generalizations
about which are the best high blood pressure drugs.
A randomized study in which some patients are selected to receive different
medications - then the results compared - is needed to definitively answer that question,
Hademenos said.
The current study "is a flashpoint. It brings to our attention something that needs to be
addressed," he said. In the meantime, Hademenos said, patients should consult their
doctors about which medications are appropriate for them.
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MAD COW DISEASE AND US
FDA Warns Livestock Feed Makers
Updated 2:24 PM ET January 11, 2001
By LAURAN NEERGAARD, AP Medical Writer
WASHINGTON (AP) - Hundreds of animal feed producers are violating rules intended
to keep mad cow disease out of the United States, prompting the government to warn
on Thursday that companies must shape up or expect shutdowns, even prosecution.
The food supply remains safe despite the violations because no cases of mad cow
disease have been found in U.S. cattle, the Food and Drug Administration said.
But the violations are serious because if the deadly brain disease does sneak into the
country, companies that don't follow the FDA's rules could spread it through animal
feed.
So the FDA warned that continued violations will prompt seizures of feed, company
shutdowns, even prosecution. Many companies already have received warning letters,
and some feed has been recalled.
"Today's food is safe," because slaughterhouse inspections have found no suspicion of
mad cow disease, FDA veterinary chief Dr. Stephen Sundlof said Thursday.
But Europe's mad-cow crisis "is not a result of them not having adequate regulations in
place - it was a problem of enforcement. And we don't want to end up like that," Sundlof
added, promising more intense inspections.
The report comes a week before the FDA, warily watching Europe's mad cow situation,
is scheduled to debate strengthening blood-donation regulations meant to keep a
human version of the disease from ever striking here.
Fear over mad cow disease, or bovine spongiform encephalopathy, arose in the
mid-1990s when Britain discovered a new version of the human Creutzfeldt-Jakob
disease apparently was caused by eating infected beef. About 80 people have died of
the new CJD disease in Britain since then, and now France, Germany and other
European countries are grappling with infected livestock.
Animals get the disease by eating the tissue of other infected animals, and British cows
are thought first to have been infected by eating feed made from sheep harboring a
similar illness.
So the livestock industry in 1996 voluntarily banned sheep and certain other animal
parts from U.S. feed. The next year, the FDA formally banned any proteins from cows,
sheep, goats, deer or elk - animals that get similar brain-wasting diseases - from feed
for cows, sheep or goats. Poultry or pigs can still eat those proteins, but feed must be
labeled "do not feed to cows or other ruminants" and companies must have systems to
prevent accidentally mixing up the feeds.
Yet FDA inspections found:
-Of 180 renderers - companies that turn slaughtered animals' parts into meat and bone
meal - that handle risky feed, 16 percent lacked warning labels and, worse, 28 percent
had no system to prevent feed mixups.
-Of 347 FDA-licensed feed mills that handle risky feed, 20 percent lacked warning
labels and 9 percent lacked mixup-prevention systems.
-Of 1,593 unlicensed feed mills that handle risky feed, almost half lacked warning
labels and 26 percent lacked mixup-prevention systems. (FDA only licenses mills that
add medications to feed.)
States are helping FDA inspect the companies, and hundreds are left to inspect. But
Sundlof pledged Thursday that every company will be inspected.
The American Feed Industry Association said it supported the FDA's enforcement of
the rules, saying most companies inspected so far are complying.
ALLERGY SHOTS IMPROVE QUALITY OF LIFE FOR ALLERGY AND ASTHMA SUFFERERS
This Doctor's Guide DGNews article has been recommended by Dr. Bruce Roseman
Title: Allergy Shots Improve Quality of Life for Allergy and Asthma Sufferers
MILWAUKEE, WI -- January 12, 2001 -- Undergoing grass pollen immunotherapy, also called "allergy shots," significantly reduces hay fever symptoms and medication requirements for allergy and asthma sufferers, according to a study in the January Journal of Allergy and Clinical Immunology (JACI).
The JACI is the peer-reviewed, scientific journal of the American Academy of Allergy, Asthma and Immunology (AAAAI).
Samantha M. Walker, Ph.D., Imperial College School of Medicine at the National Heart and Lung Institute in London, and colleagues in London, Messina and Italy observed 44 patients who have severe summer hay fever and seasonal asthma triggered by grass pollens. After observing symptoms for one summer, researchers injected 22 of the patients with a grass pollen vaccine and 22 patients with a placebo for four weeks, followed by monthly injections for two years.
Researchers compared symptom scores before and after the two-year maintenance period and found that hay fever symptom scores dropped by 49 percent in the immunotherapy group and 15 percent in the placebo group. Similarly, medication requirements fell by 80 percent in the immunotherapy group and 19 percent in the placebo group. Also, asthmatic chest symptoms, such as coughing and breathing difficulties, were reduced by 90 percent in the immunotherapy group compared with 11 percent in the placebo group.
Researchers concluded grass pollen immunotherapy followed by two years of maintenance treatment was highly effective in reducing both nasal and asthma symptoms in allergic patients and lowered the seasonal increases in airway hyperresponsiveness typically seen in allergic asthma. This effect is accompanied by a marked improvement in quality of life and patient satisfaction.
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