May 2002

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Posted Thursday, May 30, 2002 by Rick
http://www.docguide.com

Rational Design Of Anabolic Therapies For Bone Can Now Be Envisioned
A DGReview of :"High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5"
New England Journal of Medicine (NEJM)

05/22/2002
By Anne MacLennan

Molecules that interact with the gene for low-density lipoprotein receptor-related protein 5 (LRP5) may provide targets for the treatment of osteoporosis, a major public health problem of largely unknown cause.

Because loss-of-function mutations in the LRP5 gene have been shown to cause osteoporosis-pseudoglioma, Lynn M. Boyden and colleagues from University of Connecticut Health Center, Farmington, Connecticut, United States, reasoned a gain-of-function in this same gene might be linked with high bone density.

These researchers performed a series of genetic and biochemical analyses of a kindred with high bone density, a wide and deep mandible and torus palatinus.

Genetic analysis revealed an LRP5 mutation, the substitution of valine for glycine at codon 171, that segregated with the clinical findings.

In vitro studies demonstrated the defect in LRP5 resulted in changes in signaling events with other molecules that normally interact with this receptor-related protein, resulting in increased bone density.

The authors conclude the LRP5V171 mutation causes high bone density, with a thickened mandible and torus palatinus, by impairing the action of a normal antagonist of the Wnt (a developmental protein) pathway and thus increasing Wnt signaling.

A key aspect of this finding is that the rational design of anabolic therapies for bone can now be envisioned.


Methotrexate twice weekly vs once weekly in rheumatoid arthritis: a pilot double-blind, controlled study (Rheumatol Int)
http://www.docguide.com/news/content.nsf/PaperFrameSet?OpenForm&id=8B74FB5E2F132EBC852568FA005CA25A&newsid=8525697700573E1885256BC20068E461&u=GOTO//link.springer.de/link/service/journals/00296/contents/02/00186/&ref=


New Stool Test Developed For Colorectal Cancer
Lancet
05/30/2002
By Harvey McConnell

A new technique involving detection of a specific protein in faeces could prove to be a reliable marker for colorectal cancer.

Clinical evaluations are being carried out by Dr Nicholas Coleman and colleagues from the Medical Research Council Cancer Cell Unit, Cambridge University, Cambridge, England, on identifying a specific protein - minichromosome maintenance protein 2 (MCM2) - which is present in cancerous colorectal cells but not normal cells.

Dr Coleman points out that colorectal cancer screening generally includes faecal occult blood testing and flexible sigmoidoscopy, "but better tests are needed if accuracy, safety, affordability, and compliance rates are to improve." Colorectal cancer claims at least 500,000 lives a year world-wide.

Screening by detection of altered DNA in faces is labour-intensive, expensive, and may lack sensitivity because of clonal heterogeneity in colorectal carcinomas.

Minichromosome maintenance (MCM) proteins are members of the prereplication complex that is essential for DNA replication, the researchers add. They are present within the nucleus throughout the cell cycle, but are rapidly downregulated in differentiated cells. Dr Coleman and colleagues have earlier proposed that dysplastic and malignant cells could be characterized as those which remain in cell cycle, with deregulated expression of MCM proteins.

In their current trial, the researchers detected MCM2-positive cells from 37 of 40 patients known to have colorectal cancer. By contrast, there was no detection of the protein in any of the 25 healthy individuals who made up the control group.

Investigators said that their findings suggest that detection of MCM2 in colonocytes retrieved from the faecal surface might be of value in the non-invasive diagnosis of malignant colorectal disease.

They add, "The conditions of this study do not represent those of a general screening setting, and our findings might have differed in a population with a higher frequency of cancers of the right-side of the colon. Nevertheless, despite the requirement for rapid stool processing, our approach might ultimately prove suitable for population screening, either alone or in combination with other tests."


Risks For Children Given Off-Label Drugs
British Medical Journal (BMJ)

05/30/2002
By Harvey McConnell

Prescription of unlicensed and off-label drugs to children is common, carrying a high risk of adverse drug reactions.

Dr Lolkje de Jong-van den Berg, and colleagues at the University of Groningen, Netherlands, Groningen, analyzed 68,019 prescriptions for 19,283 children aged from zero to 16 years. Family doctors wrote 56,961 (83.7 percent) of the prescriptions, with the rest written by specialists. Unlicensed drugs amounted to 16.6 percent (11,288) of the total prescriptions.

Highest percentages of off label use were urological or sex hormones (mainly oral contraceptives; 85.9 percent), ophthalmological and otological drugs (79.4 percent), dermatological drugs (55.9 percent), and cardiovascular drugs (48.3 percent). In the group with the highest number of prescriptions - respiratory drugs -16.1 percent of all prescriptions were used off label.

The clinicians said that labelling for children needs to be improved.

In a second study, Dr Bruno Stricker and colleagues from the Erasmus University Medical Center, Rotterdam, randomly sampled 17,453 drug prescriptions issued by family doctors to 6,141 children according to the licensing status of the drug,

The clinicians found that 12,405 prescriptions (71 percent) were for drugs licensed for use in children. Among the remaining 5,048 (28.9 percent) prescriptions, 2,667 (15.3 percent) were for drugs not licensed for use in children and 2381 (13.6 percent) were off label prescriptions for licensed drugs

The drugs most often prescribed unlicensed, or off label, were fusidic acid (ophthalmological gel), salbutamol (aerosol), deptropine citrate, amoxicillin, and fluticasone (aerosol).

Dr Stricker , said: "Although unlicensed and off label prescribed drugs do not necessarily carry an actual threat to the health of a child, the risk of adverse drug reactions is high, as adequate dosing schemes have often not been assessed."

The researchers point out, for example, that bone demineralisation and impairment of growth may follow long term use of respiratory corticosteroids in children, and the use of highly dosed deptropine citrate in small children can cause hallucinations, agitation, ataxia, and anxiety.

Dr Sticker and colleagues said that unlicensed and off label is a situation which "is highly unsatisfactory, and efforts should be made to improve it."





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Posted Thursday, May 30, 2002 by Rick
TNF-alpha blocker Infliximab highly effective for patients with ankylosing spondylitis new
UVentures - Apr 6 2002 7:52PM GMT
Found by: Moreover
http://www.datamonitor.com/~0627b6dbbdc14aceb5710132a033cc69~/all/news/product.asp?pid=37CE0385-F44A-48FA-93CC-A3BA53E071FA

2002 Best of Education new
Despite suffering from multiple autoimmune diseases plus diabetes and rheumatoid arthritis, a Carson City fifth-grader practices jazz and tap dancing, performs in school musicals, plays soccer, and here s the real kicker maintains a 4.0 grade-point average.
Found by: FAST Search (alltheweb.com)
http://www.rgj.com/extra/bestofedawards.php

F.D.A. Panel Recommends Approval for Psoriasis Drug new
...Psoriasis is an autoimmune disease in which the body's defense system against microbial invaders attacks a person's own...- May 23 2002 Found by: Yahoo! News
http://premium.news.yahoo.com/news?tmpl=story&u=/nytp/20020524/200069&.bail=http://premium.news.yahoo.com/rd?r=Autoimmune

Autoimmune Breakdown new
ABCNEWS.com - May 30 2002 6:00AM GMT
Found by: Moreover
http://abcnews.go.com/sections/living/Healthology/Lupus_Rise020529.html

Science and Technology News and Discussion new
A drug used to treat autoimmune disorders such as rheumatoid arthritis and psoriasis may help people with patchy baldness grow their hair back.
Found by: FAST Search (alltheweb.com)
http://www.bottomquark.com/article.php?sid=2759

FDA Panel Backs Amevive Approval new
...Other treatments for psoriasis, an autoimmune disease that causes scaly skin, can be toxic....- May 23 6:14 PM ET
Found by: Yahoo! News
http://story.news.yahoo.com/news?tmpl=story&u=/ap/20020523/ap_on_he_me/biotech_decision_1

29 May 2002 new
Medivir and Peptimmune have discovered that a small molecule inhibitor of the protease enzyme Cathepsin S, suppresses the development of chronic relapsing experimental autoimmune
encephalomyelitis, or CR EAE, in an animal model of multiple sclerosis.
Found by: FAST Search (alltheweb.com)
http://www.datamonitor.com/~cf2f46530bce41759f0fd7c4a9131ac4~/all/news/product.asp?pid=2B8C0CA3-97A4-47C0-9844-CC15B1743BFA

Swallow This new
...Each year more than 11 million americans are tested for such gastrointestinal ailments as inflammatory bowel disease, gastritis and cancerous polyps....- May 30 12:20 PM ET
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http://story.news.yahoo.com/news?tmpl=story&u=/fo/20020530/bs_fo/swallow_this

Link between bowel disease and nasal problems new
HealthandAge.com - May 17 2002 6:20PM GMT
Found by: Moreover
http://www.healthandage.com/Home/gm=1!gid1=1500;jsessionid=POqJ2MJ2lq56rVbYWMpVObgclJvf5T2XD9TslhXpWOKnuIaZg6Ip!-9042643406219775639!180357125!80!7002

Crohn's disease doesn't deter graduate from realizing goal new
...But near the end of her sophomore year at Lake Worth High School, she learned that she has Crohn's disease, and suddenly, the goal seemed unreachable....- May 24 7:37 AM ET
Found by: Yahoo! News
http://dailynews.yahoo.com/h/krfortworth/20020524/lo/crohn_s_disease_doesn_t_deter_graduate_from_realizing_goal_1.html





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Posted Thursday, May 23, 2002 by Rick
Understanding Scleroderma
... a professor of rheumatology at University of California, Los Angeles, says Raynaud's syndrome is usually the first symptom of scleroderma. Raynaud's causes the hands to turn white on exposure...... hardening of the skin that causes it to feel like wood or plastic; fatigue; heartburn; shortness of breath; and painful joints. Bunis says that when her disease was......She says when you have a painful, chronic illness like scleroderma, it's easy to get
depressed, and she recommends taking anti-depressants...- May 22 11:58 PM ET
Found by: Yahoo! News
http://story.news.yahoo.com/news?tmpl=story&u=/hsn/20020523/hl_hsn/understanding_scleroderma

Immune System Balance Avoids Autoimmune Diseases new
UniSci - Apr 17 2002
Found by: Yahoo! News Full Coverage
http://unisci.com/stories/20022/0417023.htm

Biotech Paying Attention to FDA
...And it hopes the drug could be useful in other autoimmune disorders, including rheumatoid arthritis, Crohn's disease and multiple sclerosis....- May 22 5:09 PM ET
Found by: Yahoo! News
http://story.news.yahoo.com/news?tmpl=story&u=/ap/20020522/ap_on_bi_ge/biotech_decision_1

Centocor Presents Long-Term Data From Accent II Trial With Remicade(R) (infliximab) In Maintaining Fistula Closures In Crohn's Patients
New 54-week data from the ACCENT II clinical trial assessing the effectiveness of maintenance therapy with REMICADE® in sustaining closure of draining fistulas in Crohn's disease were reported today at the Digestive Disease Week meeting in San Francisco.- May 22 3:01 PM ET
Found by: Yahoo! News
http://biz.yahoo.com/iw/020522/042509.html

Factors explaining variance in perceived pain in women with fibromyalgia (BMC Musculoskel Disord)
http://www.docguide.com/news/content.nsf/PaperFrameSet?OpenForm&id=8B74FB5E2F132EBC852568FA005CA25A&newsid=8525697700573E1885256BB80055C6CB&u=GOTO//www.biomedcentral.com/1471-2474/3/12/abstract&ref=

Possible association of non-binding of HSP70 to HLA-DRB1 peptide sequences and protection from rheumatoid arthritis (Immunogenetics)
http://www.docguide.com/news/content.nsf/PaperFrameSet?OpenForm&id=8B74FB5E2F132EBC852568FA005CA25A&newsid=8525697700573E1885256BBA005E3AE1&u=GOTO//link.springer.de/link/service/journals/00251/contents/02/00444/&ref=





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Posted Friday, May 17, 2002 by Rick
Etanercept in the treatment of adult patients with Still's disease (Arthritis Rheum)
http://www.docguide.com/news/content.nsf/PaperFrameSet?OpenForm&id=8B74FB5E2F132EBC852568FA005CA25A&newsid=8525697700573E1885256BB5004DC815&u=GOTO//www3.interscience.wiley.com/cgi-bin/abstract/93519267/START&ref=





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Posted Friday, May 17, 2002 by Rick
Drug backed for Crohn's patients new
Patients with hard-to-treat Crohn's disease are more likely to achieve long-term remission if they get regular infusions of the rheumatoid drug Remicade, a new study confirms.
Found by: MSNBC
http://www.msnbc.com/news/746869.asp

Medical marijuana case takes interesting twist
...Scruggs has Crohn's disease, which causes intestinal bleeding and severe pain....- May 15 7:20 AM ET
Found by: Yahoo! News
http://dailynews.yahoo.com/h/krdenver/20020515/lo/medical_marijuana_case_takes_interesting_twist_1.html

Untitled new
... thrombocytopenic purpura and Colirest(TM), in pivotal clinical trials for the treatment of Crohn's disease and completed Phase II trials for the treatment of ulcerative colitis....- May 14 8:32 AM ET
Found by: Yahoo! News
http://biz.yahoo.com/bw/020514/142158_1.html

Given Imaging Announces Prominent Presence of M2A Capsule at Digestive Disease Week 2002
... suffering from a broad range of gastrointestinal diseases, such as, Inflammatory Bowel Disease, Crohn's Disease, Obscure Gastrointestinal Bleeding, Celiac Disease and NSAID (Non-...-
May 10 7:30 AM ET
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http://biz.yahoo.com/prnews/020510/nyf019_1.html

Untitled new
Repeat infusions of the Crohn's disease drug infliximab (Remicade) appear to keep many patients in remission and decrease their need for steroid drugs, the results of an international study show.- May 03 10:38 AM ET
Found by: Yahoo! News
http://story.news.yahoo.com/news?tmpl=story&u=/nm/20020503/hl_nm/crohns_infliximab_1

New National Psoriasis Foundation Survey Shows Psoriasis Diminishes Quality of Life for Millions
... the United States dedicated to improving the quality of life of people with psoriasis and psoriatic arthritis and their families....- May 15 10:00 AM ET Found by: Yahoo! News
http://biz.yahoo.com/prnews/020515/dcw002_1.html

Infliximab May Offer Hope for Patients Living With Spondyloarthropathy
For the first time, there may be an effective therapeutic option for severe cases of spondyloarthropathies, a group of rheumatic inflammatory diseases that affect the spinal column, peripheral joints and tendons.- Mar 11 10:01 AM ET
Found by: Yahoo! News
http://biz.yahoo.com/prnews/020311/nym015_1.html

Pop Stand: Celebrity pill-pushing needs a new RX new
That's how I've been feeling about Debbie Reynolds ever since I saw her image beaming out from behind a stage curtain on the cover of a press kit for a drug that controls "overactive bladder." And Bob Dole, since I saw him extolling the virtues of Viagra. Not to mention Kelsey Grammer and spouse, spokespeople for IBS (irritable bowel syndrome).
Found by: Minneapolis Star Tribune
http://www.startribune.com/stories/389/2819835.html





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Posted Thursday, May 9, 2002 by Rick
Etanercept Curbs Main Ills In Ankylosing Spondylitis
A DGReview of :"Treatment of Ankylosing Spondylitis by Inhibition of Tumor Necrosis Factor [Alpha]"
New England Journal of Medicine (NEJM)

05/02/2002
By Anne MacLennan


Four-month treatment with etanercept has been found to produce rapid, significant and sustained improvement in patients with ankylosing spondylitis.

This promising finding supports the concept that inhibition of tumour necrosis factor a (TFN-a) leads to clinical improvement in patients with ankylosing spondylitis, although the long-term outcome of such therapy remains unknown, as does which patients might most benefit from it.

Ankylosing spondylitis is difficult to treat and causes substantial morbidity, often decades after diagnosis, and with rates of pain and disability similar to those among people with rheumatoid arthritis. Until recently, treatment has mainly been supportive, consisting of non-steroidal anti-inflammatory drugs (NSAIDs).

Because of the central role of TFN-a in the spondyloarthritides, these authors investigated the use of etanercept, a recombinant human tumour necrosis factor receptor:Fc fusion protein, to treat this disease. Jennifer D Gorman and colleagues from the University of California, San Francisco, San Francisco, California conducted this double blind, placebo-controlled trial.

The researchers randomly assigned 40 patients with active, inflammatory ankylosing spondylitis to receive twice-weekly subcutaneous injections of either 25 mg etanercept or placebo over a period of four months.

During the trial, patients were allowed to continue taking NSAIDs, oral corticosteroids (10 mg or less per day) and disease-modifying antirheumatic drugs at stable doses.

Treatment produced significant and sustained improvement. At four months, 80 percent of the patients on etanercept versus 30 percent of those on placebo had a treatment response. There were significant improvements in measures of axial and peripheral diseases, with a rapid and sustained response to the drug.

The authors suggest marked reduction in stiffness, pain and functional limitations with this therapy are particularly promising, since these are the primary problems reported by ankylosing spondylitis patients and among the leading causes of disability.

Significant improvements also occurred in both the patients' and the doctors' global assessments of disease activity. The study findings are particularly notable because of the duration and extent of disease activity in these patients.

Despite the patients' use of NSAIDs, disease-modifying antirheumatics, prednisone or a combination of these drugs, clinical measures at baseline suggested the presence of active inflammatory disease. This study thus suggests etanercept alleviates many of the disabling symptoms of ankylosing spondylitis and can be used safely in combination with other anti-inflammatory and immunosuppressive agents.

On the one hand, the paucity of effective therapies for this disease underscores the importance of the findings. On the other hand, however, long-term studies with larger numbers of patients are key, particularly to address the issue of the possible long-term side effects of this treatment.

N Engl J Med 2002;346:1349-56. "Treatment of Ankylosing Spondylitis by Inhibition of Tumor Necrosis Factor [Alpha]"





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Posted Thursday, May 9, 2002 by Rick
Drug May Help Alleviate Spinal Arthritis new
The rheumatoid arthritis drug etanercept (Enbrel) can help ease symptoms of another type of arthritis known as ankylosing spondylitis, which primarily affects the spine, new study findings
suggest.
Found by: Yahoo! News
http://story.news.yahoo.com/news?tmpl=story&u=/nm/20020501/hl_nm/arthritis_spinal_1

New Treatment For Spinal Disorder Proves Effective In UCSF Study new
Science Daily - May 8 2002 5:44AM GMT
Found by: Moreover
http://www.sciencedaily.com/releases/2002/05/020502073534.htm

Arthritis drug 'could treat spine condition' new
BBC - May 4 2002 1:53AM GMT
Found by: Moreover
http://news.bbc.co.uk/hi/english/health/newsid_1961000/1961971.stm

Merck Announces First-quarter 2002 Earnings Per Share of 71 Cents new ... Drug Application (NDA) for ARCOXIA (etoricoxib) to the FDA to include new efficacy data for ankylosing spondylitis that will better position the product to compete successfully in the coxib class,...
Found by: Yahoo! News
http://biz.yahoo.com/bw/020418/182072_1.html

Infliximab May Offer Hope for Patients Living With Spondyloarthropathy new
... Spondyloarthropathies are a group of chronic related disorders of the joints that include ankylosing spondylitis, psoriatic arthritis, and the arthritis associated with inflammatory bowel disease...
Found by: Yahoo! News
http://biz.yahoo.com/prnews/020311/nym015_1.html

Prometheus Laboratories Inc. Announces Its Support of The 1st Annual Walk/Run for Celiac Disease new...Most people who have celiac disease are misdiagnosed as having irritable bowel syndrome (IBS), chronic fatigue syndrome, fibromyalgia, or a number of other conditions....
Found by: Yahoo! News
http://biz.yahoo.com/prnews/020418/lath003a_1.html

Drug backed for Crohn's patients new Patients with hard-to-treat Crohn's disease are more likely to achieve long-term remission if
they get regular infusions of the rheumatoid drug Remicade, a new study confirms.
Found by: MSNBC
http://www.msnbc.com/news/746869.asp

Crohn's Disease Drug Shows Long-Term Benefits new
Repeat infusions of the Crohn's disease drug infliximab (Remicade) appear to keep many patients in remission and decrease their need for steroid drugs, the results of an international study show.
Found by: Yahoo! News
http://story.news.yahoo.com/news?tmpl=story&u=/nm/20020503/hl_nm/crohns_infliximab_1

New Report From Decision Resources Finds Inflammatory Bowel Disease Market To Double By 2011 new Decision Resources announced today the release of its new report on Inflammatory Bowel Disease.
The report forecasts that sales of pharmaceuticals to treat IBD will double between 2001 and 2011 in the major pharmaceutical markets.
Found by: Yahoo! News
http://biz.yahoo.com/prnews/020506/nem010_2.html

RNA leads fund drive for Crohn's disease patient new
Chesterton Tribune - May 4 2002 9:20AM GMT
Found by: Moreover
http://chestertontribune.com/Duneland%20Community%20News/rna_leads_fund_drive_for_crohns.htm

Medical Research Study Supports Oxygen Absorption From The Stomach Following The Consumption Of SuperOxygenated Water new
... increased oxygen concentration into the portal vein could be of benefit for the treatment of inflammatory liver diseases....... from the ingestion of SuperOxygenated water can be transported from the stomach and the small bowel to the blood circulation, where it would then directly provide the energy needed by the working...
Found by: Yahoo! News
http://biz.yahoo.com/bw/020425/252218_1.html

Italian Region Backs Medical Marijuana new
- May 01 2002
Found by: Yahoo! News Full Coverage
http://story.news.yahoo.com/news?tmpl=story&cid=571&571&e=6&u=/nm/20020501/hl_nm/marijuana_legalization_1

Medical marijuana program thrown for a loop when U.S. refused to supply seeds new
CNEWS - May 8 2002 7:59AM GMT
Found by: Moreover
http://www.canoe.ca/NationalTicker/CANOE-wire.McLellan-Marijuana.html

Biogen Launches PsoriasisSupport.com new
... of the National Psoriasis Foundation that provides the latest information on psoriasis and psoriatic arthritis....
Found by: Yahoo! News
http://biz.yahoo.com/cnw/020501/ma_biogen_psoriasis_1.html

World's Vaccine Experts Meeting in Baltimore to Report New Progress in Vaccine Development new
... infections are also associated with post-streptococcal syndromes, including rheumatic fever, arthritis, and kidney and nervous system disorders....... evidence of rhematogenicity or nephritogenicity and there was no induction of human tissue-reactive antibodies....
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http://biz.yahoo.com/prnews/020506/dcf006a_2.html

European Commission Approves Amgen's Kineret for the Treatment of Rheumatoid Arthritis new
Amgen today announced that the European Commission has approved Kineret(R) for the treatment of the signs and symptoms of rheumatoid arthritis in combination with methotrexate, in patients with an inadequate response to methotrexate alone.
Found by: Yahoo! News
http://biz.yahoo.com/bw/020313/130024_1.html

Victims Do have Recourse Says Food Safety Attorney new
...Other people who survive the acute illness can develop Reiter's syndrome, a debilitating arthritic condition....
Found by: Yahoo! News
http://biz.yahoo.com/bw/020219/190444_1.html





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Posted Wednesday, May 8, 2002 by Rick
Chicago -- The AMA House of Delegates approved a resolution calling
for the Association to collect and disseminate information about
effective pain management education for medical schools and
residency programs. The AMA also will encourage organizations to
support voluntary continuing education for physicians, based on
effective pain management guidelines.
http://www.ama-assn.org/sci-pubs/amnews/pick_01/prse0709.htm

Posted to RISG-L List by Ray@risg.org





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Posted Friday, May 3, 2002 by Rick
http://www.canoe.ca/WorldTicker/CANOE-wire.Virtual-Patients.html

March 11, 2002
'Virtual patients' may help develop new drugs, but some experts are skeptical
WASHINGTON (AP) -- Bill and Allen both have asthma, but scientists ran into a problem when testing a highly touted experimental drug on them: The drug flunked. It didn't help Allen breathe better, and Bill had a weird reaction that called into question the drug's entire foundation.
That was good news, actually. Bill and Allen are "virtual patients," sophisticated computer programs that mimic disease. That the experimental drug failed on them meant maker Aventis Pharma didn't have to watch it fail in tests using real people -- as a competitor did.

You've heard of "in vitro" and "in vivo" research, studies in test tubes and living organisms. Welcome to "in silico" research, where companies like Entelos Inc. and Physiome Sciences put reams of biological data into supercomputers to create intricate models of human cells, organs, even multiorgan systems that mimic complex diseases.
Just as simulators help build better jumbo jets, the hope is that biosimulation will save pharmaceutical companies time and money in creating new drugs -- by helping them pick the most promising chemicals to test in people and skip dead-ends.
"This is an incredible tool for drug discovery," says Richard Kahn, chief medical officer of the American Diabetes Association. "It is absolutely astounding what this technology can do."
Dismayed that "the pipeline is about empty" of promising new diabetes drugs, the nonprofit group just began an unprecedented collaboration with Entelos, hoping to sign up pharmaceutical companies in the hunt for therapies using the California company's new diabetes simulator.
Many scientists fear biosimulators are over-hyped, particularly their role in very complex disorders like diabetes and heart disease where much of the basic biology is still a mystery.
"I don't think we're anywhere near being able to predict from a few pathways in the human cell ... things that take place in the whole body," says Dr. Jan Breslow, a Rockefeller University specialist on the pathophysiology of heart disease.
But simulators can be updated easily, says Jeremy Levin, whose New Jersey-based Physiome Sciences boasts a heart model that goes into irregular beats and customizable simulators.
Indeed, some drug giants are spending millions for access to simulators in hopes they'll improve a bad statistic: A third of potential drugs that pass the years of research needed to begin final-stage testing in people still ultimately fail.
Scientists' brains simply can't hold all the discoveries about how healthy and diseased cells work, much less envision all the chain reactions sparked by tweaking even one link in the process. But a supercomputer can.
Consider Entelos' model of asthma. Company scientists converted findings from thousands of asthma studies into mathematical formulas that a computer can read. The data link the known pathways of the respiratory inflammation of an asthma attack.
Then Entelos tested a prominent theory that hindering production of a protein called interleukin-5 would in turn lower airway-blocking cells called eosinophils during an asthma attack. Aventis had created an anti-IL5 drug that worked in animals. Now enter Bill and Allen, the virtual patients.
The drug almost eliminated eosinophils in Allen's airways but he didn't breathe any easier. Bill's asthma attack, slightly different because Entelos mimicked Aventis' animal discoveries, went haywire, casting further doubt. Shortly after the computer experiment, competing scientists reported anti-IL5 failed in a human test, too.
No one yet knows how well Entelos' new simulator for diabetes, a much more complex disease, will work. But the diabetes association's Kahn says for the first time scientists can predict "if I change X in the liver, what happens to Y in muscle," before tests in people.
Even their staunchest proponents don't expect biosimulators to ever replace human testing of drugs, required by the Food and Drug Administration. Computers can't predict what they aren't asked. Physiome, for example, once predicted the blood pressure drug Posicor wouldn't cause a certain irregular heartbeat -- but the drug later was yanked off the market for deadly interactions with other medicines.
"There is no virtual human," Levin cautions. But with more simulators being developed, the next step is integrating them so if a drug for one organ hurts another, there might be a hint. "It's a wonderful moment for this area."
On the Net:
Entelos Inc., http://www.entelos.com
Physiome Sciences, http://www.physiome.com





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Posted Thursday, May 2, 2002 by Rick
Clinical, immunological, and immunogenetic aspects of autoantibody production against Ro/SSA, La/SSB and their linear epitopes in primary Sjögren's syndrome (pSS): a European multicentre study
http://ard.bmjjournals.com/cgi/content/abstract/61/5/398

Bowel Finding Suggests Autism Is Autoimmune Disorder - new 76%
UniSci - May 1 2002 7:18AM GMT
Found by: Moreover
http://unisci.com/stories/20022/0430023.htm

Report on chronic fatigue fuels row - new 70%
Melbourne Age - Apr 28 2002 2:08PM GMT
Found by: Moreover
http://www.theage.com.au/articles/2002/04/28/1019441323251.html

Manmade DNA May Ease Bowel Disease - new 70%
Found by: Yahoo! News
http://story.news.yahoo.com/news?tmpl=story&u=/hsn/20020430/hl_hsn/manmade_dna_may_ease_bowel_disease

Biogen teams up with UK's Celltech - new 76%
Biogen Inc. yesterday said it would partner with a British company to develop and market a drug, CDP 571, that is in late stages of human testing for Crohn's disease, an inflammatory bowel disorder.
Found by: The Boston Globe
http://www.boston.com/dailyglobe2/115/business/Biogen_teams_up_with_UK_s_Celltech+.shtml

Italian Region Backs Medical Marijuana - new 78%
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The Myth of 'Harmless' Marijuana - new 56%
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http://www.washingtonpost.com/wp-dyn/articles/A11915-2002Apr30.html

News - Combining lesional short-contact dithranol therapy of psoriasis with a potent topical - new 70%
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http://www.docguide.com/news/content.nsf/news/8525697700573E1885256BA600636DB8?OpenDocument&id=48DDE4A73E09A969852568880078C249&c=Psoriasis&count=10





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Posted Thursday, May 2, 2002 by Rick
Forty patients with active, inflammatory ankylosing spondylitis were randomly assigned to receive twice-weekly subcutaneous injections of etanercept (25 mg) or placebo for four months.....At four months, 80 percent of the patients in the etanercept group had a treatment response, as compared with 30 percent of those in the placebo group (P=0.004). Improvements over base-line values for various measures of disease activity, including morning
stiffness, spinal pain, functioning, quality of life, enthesitis, chest expansion, erythrocyte sedimentation rate, and C-reactive protein, were significantly greater in the etanercept group. Longitudinal analysis showed that the treatment response was rapid and did not diminish over time.
Etanercept was well tolerated, with no significant differences in rates of adverse events between the two groups>>
For full abstract:

http://content.nejm.org/cgi/content/short/346/18/1349?query=TOC

Uploaded to RISG-L by Grannyof9





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Posted Thursday, May 2, 2002 by Rick
From Doctors Guide.
Co-occurrence of spondyloarthropathy and connective tissue disease: Development of Sjögren's syndrome and mixed connective tissue disease (MCTD) in a patient with ankylosing spondylitis

J. Brandt1, T. Maier2, M. Rudwaleit1, U. Kühl3, F. Hiepe4, J. Sieper1,5, J. Braun1,6

1Medical Department I, Rheumatology, 2Medical Department IV, Nephrology, and 3Medical Department II, Cardiology, Benjamin Franklin Hospital, Free University of Berlin; 4Rheumatology, Charité, Humboldt University, Berlin; 5Epidemiology Department, German Rheumatism Research Center Berlin, Berlin; 6Center of Rheumatology Ruhrgebiet, Herne, Germany.

ABSTRACT
Spondylarthropathies (SpA) and connective tissue diseases (CTD) are clinically distinct entities which, at first glance, seem to have little in common. However, a link between SpA and CTD has recently been suggested by a study in which a higher prevalence of Sjögren.s syndrome (SS) and sicca symptoms was reported in patients with ankylosing spondylitis (AS) and undifferentiated SpA (1). Another link between SpA and CTD is a possible side effect of a DMARD widely used to treat SpA: sulfasalazine (SAS). SAS was reported to induce antinuclear antibodies (ANA) and systemic lupus erythematosus (SLE)-like syndromes such as drug-induced lupus.
This report describes a 54-year-old white male, HLA B27-positive AS patient with some syndesmophytes who, after 15 years of disease, developed SS with salivary gland involvement, Raynaud's syndrome and anti-Ro antibodies. Then, 20 years after the onset of AS, he became acutely ill, suffering severe myositis and myocarditis along with swollen hands and highly elevated autoantibody titers recognizing U1RNP; his condition was interpreted as mixed connective tissue disease (MCTD).
The patient had been treated with SAS and azathioprine (AZA) alone several times during the last years because he had not tolerated other DMARDs. A combination of both drugs had been prescribed 3 weeks before a severe flair because of progredient high disease activity with painful peripheral arthritis of the MCP and PIP joints which, however, had not shown radiographic erosions. We describe the rare development of MCTD in an AS patient and report, for the first time, the onset of MCTD potentially triggered by sulfasalazine.