Friday, August 22, 2008

Creutzfeldt Jakob Disease and Veterans and how they are treated at death

Creutzfeldt Jakob Disease and Veterans and how they are treated at death


Hospital released vet who refused study
Widow sees priority as research, not care
Audrey Hudson (Contact)
Friday, August 22, 2008


An Army veteran seeking treatment for his sudden loss of motor skills was turned away from a veterans hospital in the Bronx, N.Y., in May 2007 after he refused to participate in a human subject experiment on Alzheimer's disease.

Joe Fitzgerald, 74, died of Creutzfeldt-Jakob disease - the human form of mad cow disease - less than a month after being dismissed without diagnosis from James J. Peters VA Medical Center.

His widow is demanding answers from the Department of Veterans Affairs (VA) as to whether human research testing is taking a priority over the health care of veterans at its hospitals.

"I want them to be held accountable for this, to prevent this from happening to someone else," Aimee Fitzgerald said. "Nothing could have saved Joe, but the care there was hateful and incompetent."

Mrs. Fitzgerald said the research study doctor, Christine Bergmann, told the family that her husband's participation in the study would enable researchers to make a quicker diagnosis of his condition.

But VA officials said Dr. Bergmann did not have the authority to offer a diagnosis.

"[The study] has very little to do with their diagnosis, and it is not consistent with what occurred," said MaryAnn Musumeci, director of the Bronx hospital.

"That's mind-boggling. That's not true," Mrs. Fitzgerald said. "Dr. Bergmann made it very clear to us that the benefit of signing up for the study would be that she would develop an individual profile of Joe that would help them to arrive at a diagnosis faster."

The VA made several officials available for comment, but not Dr. Bergmann.

VA officials and the Fitzgerald family also differ over the circumstances of Mr. Fitzgerald's discharge and whether the hospital provided care.



Miss Musumeci said Mr. Fitzgerald was admitted only for testing and clinical evaluation and that he was referred back to his physician at Castle Point VA Hospital for further care and testing.

"He was released because his work-up was complete. We did all the tests we could have done," Miss Musumeci said.

In an interview with The Washington Times, VA officials said they knew Mr. Fitzgerald was suffering from a rapidly debilitating disease.

Asked why the hospital released instead of treating the veteran, Miss Musumeci said, "He was in need of hospice care, and that is what Castle Point provides."

Castle Point VA Hospital, a part of the VA Hudson Valley Healthcare System in Dutchess County, N.Y., does not identify itself as a hospice facility and does not advertise its hospice care among its patient services.

Mrs. Fitzgerald said she was advised to keep future testing appointments with Castle Point and that the Bronx hospital never recommended hospice care or said they knew her husband's health was deteriorating.

Mr. Fitzgerald's discharge papers stated that he was in stable condition.

The Bronx VA hospital incident is the latest to raise questions about the ethics of human subject research experiments conducted at VA facilities nationwide.

A recent investigation of experiments conducted at an Arkansas veterans hospital uncovered rampant violations, including missing consent forms, secret HIV testing and failure to report more than 100 deaths of subjects participating in studies.


PHOTOGRAPH PROVIDED BY FITZGERALD FAMILY UNDIAGNOSED: Joe Fitzgerald, 74, died in June 2007, less than a month after being turned away.

Moreover, Iraq war veteran James Elliott told a congressional committee in July that he sought treatment from the VA for post-traumatic stress disorder (PTSD) and instead was persuaded to join a smoking-cessation study. While taking a smoking-cessation drug, he suffered a psychotic episode.



Mr. Elliott said the first doctor he visited at the Central Arkansas Veterans Healthcare System in Little Rock to seek treatment for PTSD "wasn't concerned about my day-to-day life. ... He wasn't concerned with my wartime experiences. He wasn't concerned about if I was going to make it home safely after the appointment."

Arthur Caplan, one of the nation's premier medical ethicists and director of the Center for Bioethics at the University of Pennsylvania, said the first obligation of any caregiver is to treat the patient.

"It is only when there is no therapy, or the therapy that is available is of doubtful utility, that someone can be recruited to research," Mr. Caplan said.

"Every researcher and every institution that does research must be sure to make an accurate diagnosis of a patient, to then offer them whatever therapy is available at the institution, to give them all their options in terms of treatment anywhere else and then and only then to pursue the possibility of trying something new in a research study," Mr. Caplan said.

"No one should ever be penalized for failing to volunteer for a study, ever," Mr. Caplan said.

"The goal of any medical encounter must be first and foremost to provide the latest and best care when care is available," Mr. Caplan said. "The chance to participate as a subject in research has to take a secondary role to receiving care as a patient."

Miss Musumeci, director of the Bronx hospital and a registered nurse, said participation in the studies is routinely offered to patients seeking care at the VA facility, including healthy patients who may be admitted to studies as control subjects.

Mary Sano, the Bronx hospital's director of research, said that "the opportunity to participate in research is widespread" and does not interfere with clinical treatment.


PHOTOGRAPH PROVIDED BY FITZGERALD FAMILY Veteran Joe Fitzgerald refused to participate in a human subject experiment on Alzheimer's disease at the James J. Peters VA Medical Center in the Bronx, N.Y.

"The research team is completely independent of the clinical team, and the clinical team has priority and determines if a person is approachable," Miss Sano said. "If they say no, the research team goes away."

Miss Musumeci said that many hospital patients welcome the opportunity to participate in studies because "they appreciate the opportunity to stay busy."

Mrs. Fitzgerald said the VA researchers wanted her husband to enroll in the Alzheimer's experiment to observe the natural and ravaging course of the disease and his eventual death.

Vera Sharav, president and founder of the Alliance for Human Research Protection, a patient-advocacy group, said the circumstances faced by the Fitzgerald family are "not unique."

"You come to a hospital in critical need and you want care, even if you are not cured, and instead they say they are going to observe the degeneration and death?"



http://washingtontimes.com/news/2008/aug/22/hospital-released-vet-who-refused-study/


http://washingtontimes.com/news/2008/aug/22/hospital-released-vet-who-refused-study/?page=2


http://washingtontimes.com/news/2008/aug/22/hospital-released-vet-who-refused-study/?page=3



CJD STAFF SGT. JAMES ALFORD 25



http://www.blackfive.net/main/2004/10/a_dying_hero_ss.html



http://www.blackfive.net/main/2004/03/ssg_james_alfor.html



http://brain.hastypastry.net/forums/archive/index.php/t-3238.html




Posted by: Sgt. B. January 25, 2005 at 10:34 AM

Friday, 11/03/06

Soldier's battle with disease continues to surprise family
Brain-wasting rarity ended career in 2003

By LEON ALLIGOOD
Staff Writer


James Alford turned 28 on Thursday under the watchful gaze of his parents, John and Gail.

No one expected that day would come, most certainly not the cadre of doctors who have examined him in the past three and a half years.

The physicians, every one of them, said he would die — and sooner rather than later.

In summer 2003, when Alford was 24 and a Green Beret based at Fort Campbell, he was diagnosed with the human variant of mad-cow disease, Creutzfeldt-Jakob disease.

The rare brain disorder produces severe behavior changes, failing memory, a loss of mobility and eventually leads to a coma and death.

But the decorated soldier, a veteran of fighting in Afghanistan and Iraq who was initially stripped of his Green Beret because of his illness, is still among the living, defying all expectations.

"I honestly don't know why he's still with us," Gail Alford said via phone from her family's home in Karnack, Texas. Jamie, as the parents call their son, has lived with them since he was diagnosed.

"In June of 2003 they told us he wouldn't see his 25th birthday; then in August they were absolutely certain he wouldn't be here at Christmas.

"Here we are at his fourth birthday since he was diagnosed. I'm not ready to say anything about having a fourth Christmas with him, but we're headed in that direction."

Alford was assigned to the U.S. Army's 5th Special Forces Group. His illness was chronicled in a front-page story in The Tennessean in November 2003.

According to the Creutzfeldt-Jakob Foundation, the incidence of CJD in the United States is one case per 9,000 adults age 55 and older; it occurs much less frequently in people 30 and younger.

The disease can be contracted by contamination during surgery or inherited at birth, but 85 percent of cases are of the "sporadic" variety, meaning the cause for the disease is unknown, the CJD Foundation reported. That's the case in Alford's situation.

Because he was so well traveled as a Special Forces soldier, his family said he may have eaten contaminated beef in England, where more than 125 persons have contracted the disease after eating beef from cows that were fed products rendered from scrapie-infected sheep. Scrapie is a form of a brain disorder found in sheep.

The soldier also told his family that in 2001 he ate a sheep's brain while stationed in Oman. However, while the disease is linked to cattle that have eaten sheep-byproducts, there has been no evidence of direct transfer from sheep to humans, according to the CJD Foundation.

Alford was a stellar soldier until 2003 when his unit went to Iraq. Less than a year after earning a Bronze Star in Afghanistan, the staff sergeant became a foul-up of his unit.

His inability to stay on task prompted his commander to order him to keep a pad and pen handy on which to write down orders. He was demoted in rank and in April 2003 was sent home from Iraq to be drummed out of the Special Forces.

After Alford was diagnosed with the fatal disease the Army made amends, restoring the soldier's rank and making it retroactive to the day of his demotion. But his soldiering days were over.

Today, Alford sleeps on a hospital bed at his parents' home. A nurse helps his mother and father care for their son.

"He's still conscious. He will still look at his dad and I and the nurse. He'll track us with his eyes. That's the most response we get from him," Gail Alford said.

Music or movies are playing almost all the time in his room. The doctors tell the family "it's good stimulation." He receives nourishment through a feeding tube and is given supplemental oxygen to help him breathe.

"He's got everybody fooled, and we're certainly glad," said John Alford.

"You just don't really know why he's hung on as long as he has. If I had to sum it up, I would guess it would be he's hanging on for mine and Gail's sake. I don't know. There's no medical reason at all for this."

The father, a retired Army man himself, said the staff sergeant's military buddies call and visit often.

"They come by when they can, if they get leave, or if they're in the area. Sometimes they have dinner. Sometimes they just sit and visit with Jamie. They haven't deserted him," John Alford said.

"We just take it day by day, doing the best we can with what we've got," added Gail Alford. •



http://www.fairviewobserver.com/apps/pbcs.dll/article?AID=/20061103/COUNTY05/611030402/1321/MTCN06


http://www.blackfive.net/main/2004/10/a_dying_hero_ss.html



Subject: O'Reilly FACTOR HELPING SPECIAL FORCES WAR HERO DYING HIDEOS DEATH AFTER BEING DEMOTED CJD (AKA MAD COW DISEASE)
Date: December 6, 2003 at 6:31 pm PST


-------- Original Message --------
Subject: [Fwd: [CJDVoice] Re: SPECIAL FORCES WAR HERO DYING HIDEOS DEATH AFTER BEING DEMOTED (AKA MAD COW DISEASE)]
Date: Sat, 06 Dec 2003 16:05:48 -0600
From: "Terry S. Singeltary Sr."


Friday, December 05, 2003

This is a partial transcript from The O'Reilly Factor, December 4, 2003.


Watch The O'Reilly Factor weeknights at 8 p.m. and 11 p.m. ET and listen
to the Radio Factor!


BILL O'REILLY, HOST: In the Personal Story segment tonight, the tragic saga of 25-year-old Green Beret James Alford.

In 2001, the staff sergeant was assigned duty in the country of Oman, and, while there, he ate a traditional dinner of goat brains. About a year later, Alford's behavior began to get bizarre, and he was demoted in rank. Despite that, the Army deployed him to Iraq in January 2003, but his health continued to decline, as did his behavior. Finally, in April 2003, he was sent to Fort Campbell in Kentucky to be court-martialed and kicked out of the Special Forces. But, while there, doctors made a startling discovery. James Alford had mad cow disease, which causes progressive dementia. His brain was literally being eaten away.

The Army then declared Alford medically incompetent and began processing his retirement. They also reinstated his rank.

But his family says there are still problems. What a mess. Joining us now from Dallas are the parents of Staff Sergeant Alford, retired Sergeant Major John Alford and his wife, Gail. Also, from Boston, Fox News Military Analyst Colonel David Hunt. Sergeant Alford, first, we want to ask you about James. How's he doing right now?

SGT. MAJ. JOHN ALFORD, FATHER OF GREEN BERET: He's about the same that he has been lately. He's not doing any better. He's sleeping quite a bit more. Sometimes he sleeps by day and stays awake all night, but we've just adjusted to that.

O'REILLY: All right. Can you carry on a conversation with him? Is he lucid?

JOHN ALFORD: No, sir. We talk to him. We talk to him just as if he was coherent, and I think he hears us, but he cannot answer us. He cannot communicate in any way.

O'REILLY: All right. So he's in like a vegetative state here, that you have to care for him, feed him, and all of that?

JOHN ALFORD: Yes, sir. He's fed through a tube, but he does take some foods orally, baby foods, and some foods that we process ourselves.

O'REILLY: All right. So he's in bed all the time.

JOHN ALFORD: Yes, sir.

O'REILLY: You have to take care of him, make sure he's alive. Now this is not going to change, right? You can't turn this around, correct?

JOHN ALFORD: No, sir. As far as we know, we cannot.

O'REILLY: All right. Now, Mrs. Alford, what do you want to see happen here?

GAIL ALFORD, MOTHER OF GREEN BERET: I want my son to remain on active duty until his death, and I want his durable power of attorney that he initiated for me prior to being deployed to be honored by the Army.

O'REILLY: What does that mean, though, in concrete terms for you?

GAIL ALFORD: In concrete terms, I want them to fully reinstate his pay and to honor it completely.

O'REILLY: All right, but his rank has been reinstated. I assume he's gotten the back pay that he...

JOHN ALFORD: No.

O'REILLY: No? He hasn't gotten the back pay yet?

GAIL ALFORD: No.

JOHN ALFORD: No. They took him back to his E-6 -- his staff sergeant pay grade, but they're still processing and working on his back pay, and we assume it will be forthcoming.

O'REILLY: Yes, the Army tells us it will be.

JOHN ALFORD: Yes.

O'REILLY: So I wouldn't worry about the financial end of it.

JOHN ALFORD: Yes, but what we're concerned with now -- his pay has been frozen, and it was released temporarily pending my wife being appointed guardian, and then they're only going to pay 80 percent of his pay.

O'REILLY: All right.

JOHN ALFORD: He's an American soldier and he's entitled to it.

O'REILLY: You're right. Got it. You think that he was wounded in the line of duty because, you know, you eat this stuff over in a country where you're posted, so he should get full pay until he's deceased?

JOHN ALFORD: Yes, sir.

O'REILLY: All right.

JOHN ALFORD: And medical benefits.

O'REILLY: And medical benefits. Well, we assume that the V.A. is taking care of him, are they not?

JOHN ALFORD: Well, sir, they would. We want our son to be provided the best medical care available, and we would like to see that either in a military medical facility, not a V.A. hospital, but a military medical facility or a commercial hospital. If he is retired as they're trying to do, he can be treated in a civilian facility, but they will only pay 80 percent of it.

O'REILLY: Eighty percent of it, all right.

JOHN ALFORD: Yes, sir.

O'REILLY: Now, Colonel Hunt, you're heard this terrible story. I mean everybody watching it now -- this poor guy goes over there, and, through no fault of his own, I mean, what is he, 27, 28 years old.

COL. DAVID HUNT (RET.), U.S. ARMY: Twenty-five.

O'REILLY: Well, I think that was when he was -- OK.

JOHN ALFORD: No, sir. He celebrated his 25th birthday three Sundays ago.

O'REILLY: All right. So he's 25 -- geez, just 25 years old. Amazing. So, anyway, he's going to die. And, you know, what do you do? What should the Army do here?

HUNT: This the worst case of abuse of a soldier I've seen in 30 years.

O'REILLY: Really?

HUNT: I have never seen, heard, read, dreamed that the United States Army, that this Special Forces group that I'm a proud member of, a historic unit, would treat another human being, a soldier, a Special Forces soldier like this. The last thing this great kid remembers is the Army called him a liar.

What they've got to do is get the chief of staff of the Army -- this has got to happen fast. He doesn't have a lot of time. His parents -- his mother -- his father is a 34-year veteran of the military, his mother is a nine-year veteran in the military, and his wife is a three-year veteran.

The power of attorney is so stupid, they deployed over in Iraq together, so they had to have a power of attorney with somebody else.

The Army has made a mistake every step of the way. This guy made staff sergeant in five years. It takes normally seven to 10 years.

He got sick, by the way, not at Fort Campbell, but trying out for Delta Force. Besides SEAL Team 6, the Army's Delta Force, the premier counter-terrorism unit in the world. That's the kind of guy he is, four-time volunteer, Bronze Star medal-winner in Afghanistan, goes to Iraq, and they treat him like dirt.

And they're still doing it to his family. This is the biggest outrage I have ever heard of in 30 years.

O'REILLY: So we need to contact the head of the Army right now, right?

HUNT: They ought to get this fixed. There's a great guy who's a deputy commander at 5th Special Forces group, who heard about this in the paper.

This wouldn't have been done without Fox News and The O'Reilly Factor doing this and some local papers writing about it. And they need rank to push this fast.

It's got to be fixed immediately, it will take about a four-star general, pick up the phone, talk to this man's family, 34-year veteran father, a sergeant major, and a nine-year veteran mother and fix it now.

O'REILLY: All right. Well, we can make that happen. I think we can make that happen. So he should get full back pay right away, and he should get into the best medical facility the government can provide and they should pay 100 percent of it, right?

HUNT: Absolutely. Absolutely. And they can do that, exceptions, it doesn't matter, take care of this guy now.

O'REILLY: All right. And that would be OK with you folks if we get your full pay coming in and then the best medical facility the government can provide a hundred-percent paid?

JOHN ALFORD: Sir, that's what we're asking for, that and respect and honor the power of attorney, not just for my son, but if he's having this problem, we're having this problem -- we're losing people every day in Iraq, and there's got to be a lot of other families having the same trouble and don't know what to do about it.

O'REILLY: All right. Well, let's work on this first, and then we'll get to the other problem.

All right. Well, we're going to work with Colonel Hunt, and we're going to try to get a definitive word by Monday. You know, we'll give the Army a little time to cut through the bureaucracy, but I think we'll work it out. I really do, and if we don't...

HUNT: I do, too.

O'REILLY: Yes. If we don't it ain't going to be good. All right. Mr. and Mrs. Alford, we want you to have a very merry Christmas, and we're very sad that this happened to your son.

HUNT: God bless the family.

O'REILLY: And we will try to do everything we can for you. And, Colonel, as always, we appreciate it.

And we'll have an update on Monday about this situation



http://www.foxnews.com/story/0,2933,105003,00.html



-------- Original Message --------
Subject: [CJDVoice] Re: SPECIAL FORCES WAR HERO DYING HIDEOS DEATH AFTER BEING DEMOTED (AKA MAD COW DISEASE)
Date: Fri, 05 Dec 2003 14:21:34 -0600
From: "Terry S. Singeltary Sr."
Reply-To: cjdvoice@YAHOOGROUPS.COM
To: OREILLY@FOXNEWS.COM
CC: CJDVOICE
References: <3fc22f84.6040305@wt.net>


Hello again Bill,

I heard you ran a story last night on our war hero and CJD and what the Gov. did to him. I want to thank you, We all want to thank you. I am sorry to say I missed the show. Is there any transcript of the show we can locate on the www (url)? if so I would very much like to read it. again, many many thanks. BUT, there are many more out there that the Gov. is refusing to acknowledge. I only hope that you continue to pursuit and keep a close eye on this issue of human/animal TSEs aka mad cow disease in the USA, _especially_ the sporadic CJDs and the continued denial and flat refusal to rapid test USA cattle for TSEs and to refuse to make CJD reportable Nationally ASAP...

again, many thanks,

I am sincerely,

Terry S. Singeltary Sr.

Terry S. Singeltary Sr. wrote:



------ Original Message --------

Subject: SPECIAL FORCES WAR HERO DYING HIDEOS DEATH AFTER BEING DEMOTED (AKA MAD COW DISEASE)
Date: Mon, 24 Nov 2003 10:19:16 -0600
From: "Terry S. Singeltary Sr."
To: OREILLY@FOXNEWS.COM


Hey Bill, maybe you can help this family out. After this soldier being a special forces war hero, and then left to die a most hideous death, this is not right. Another thing, this is a 25 year old dying from sporadic CJD. please do not let the Government confuse you with the myth that sporadic CJD just falls from the sky with no route and source. This is total crap......please help this family;

Family of dying GI battles bureaucracy

Associated Press

KARNACK - By the time he shipped out for the war in Iraq in January, Special Forces Sgt. James Alford was a wreck of a soldier.

For five months, he had been doing odd things. He disappeared from Fort Campbell, Ky., for several days. He lost equipment and lied to superiors. In December, he was demoted from staff sergeant to sergeant.

In the Kuwaiti desert, he came apart. The hotshot Green Beret, who a year earlier ran circles around his team members and earned a Bronze Star in Afghanistan, was ordered to carry a notepad to remember orders. By March, he was being cited for dereliction of duty, larceny and lying to superiors. He couldn't even keep up with his gas mask.

Finally, in April, his commanders had had enough. They ordered him to return to Fort Campbell to be court-martialed and kicked out of the Special Forces.

"Your conduct is inconsistent with the integrity and professionalism required by a Special Forces soldier," Lt. Col. Christopher Conner of the 2nd Battalion, 5th Special Forces Group Headquarters in Kuwait wrote April 10.

Confused and disgraced, the soldier moved back into his off-base home, where he ate canned meat and anchovies, unaware of the day, the month or the year.

Sensing something was wrong, a neighbor called Alford's parents. They drove 600 miles from East Texas to find a son who had lost 30 pounds and could no longer drink from a glass, use a telephone, button his shirt or say "Amber," the name of his soldier wife, who was still stationed in the Middle East.

They rushed him to an emergency room. A month and several hospitals later, Alford's family learned that he was dying of a disease eating away his brain. He had Creutzfeldt-Jakob disease, an extremely rare and fatal degenerative brain disorder akin to mad cow disease that causes rapid, progressive dementia.

Now, as the 25-year-old soldier wastes away in his boyhood home, his parents and his wife are struggling to understand how the military could have misdiagnosed Alford's erratic, forgetful behavior as nothing more than the symptoms of a sloppy, incompetent soldier.

"He had to hold his hands to keep them from shaking, but they saw nothing wrong with my child," his mother, Gail Alford, a nine-year Army veteran, said recently from her home in Karnack, a rural community near Marshall.

Alford's parents say Special Forces staff members told them that a doctor in Kuwait had found nothing wrong with him and that a psychiatrist there had said Alford was "faking it."

Army officials have acknowledged that the 5th Special Forces Group erred and, more than eight months after Alford's demotion, they reinstated his staff sergeant rank.

But the dying soldier's family members want more. They want a public apology for the ridicule and disgrace that they say filled Alford's final days of service.

"They called him stupid, told him he was lazy, he was a liar, that he wasn't any good, that he was a faker," his mother said, recalling what little her son could tell her about his time in Kuwait. "I want them shamed the way they shamed my son."

And they want his pay restored and his medical benefits maintained. The Army declared Alford medically incompetent, placed him on retirement status and froze his pay this month until his parents can prove in court that they are his legal guardians. His mother said she was given power of attorney long ago.

Special Forces blamed

Alford's father, retired Army Command Sgt. Maj. John Alford, who served 34 years, said that Army doctors have been caring and professional and that commanders stationed his son's wife, Spc. Amber Alford, in Texas near her husband.

He mainly faults the Special Forces.

"I think they did everything they could to break him, mentally and physically," he said.

A Special Forces spokesman did not respond to phone messages and an e-mail request for an interview with The Associated Press.

In a July 30 letter responding to an inquiry by U.S. Rep. Max Sandlin, D-Marshall, Army Lt. Col. Johan Haraldsen wrote that the Special Forces group to which Alford belonged expressed "its deepest concerns" to the soldier and his family.

"All actions taken ... involving Sergeant Alford were appropriate based on the best information available at that time," Haraldsen wrote.

Alford himself may have tried to conceal his symptoms, said Dr. Steve Williams, a clinical fellow in the division of infectious diseases at Vanderbilt University Medical Center in Nashville, Tenn.

"He was capable of masking the symptoms because he was resourceful and he was a smart guy," said Williams, who diagnosed Alford with Creutzfeldt-Jakob. "I'd ask him what floor he was on, and I could catch him looking outside and counting the number of windows."

Doctors believe that Alford has the classic form of the disease, which develops spontaneously. It affects one in 100 million people under 30, according to the Centers for Disease Control and Prevention.

Col. David Dooley, an infectious-disease doctor at Brooke Army Medical Center in San Antonio, said Special Forces staff members shouldn't take the blame for missing Alford's illness. A delayed diagnosis is "typical and classic"; the average lag time for the disease is five to seven months, he said.

"If I'm going to hold anything against them, they might have come around a little faster when a medical problem was recognized," Dooley said. "The Special Forces group was fairly inert to the face of data that we medics were showing them."

Alford's parents believe that he has the variant form of the disease, caused by eating brains or nervous-system tissue from an infected cow. They worry that he may have gotten it from eating sheep brains locals served to soldiers as an honor in Oman two years ago.

But there is no evidence that people can get the disease from sheep.

Doctors also note that Alford didn't have the outbursts of anger and depression usually associated with the variant form and that the fast progression of his illness is more consistent with the classic form.

Losing everything

Alford was the youngest man in the 5th Special Forces Group, and his wife says some of his team members resented his promotion. At least one said Alford seemed a bit immature and made a few bad decisions when he first joined, but military records show that he earned decorations.

He was awarded the Bronze Star in May 2002 for "gallant conduct" in leading reconnaissance patrols in the southern Afghan city of Kandahar and helping capture Iranian terrorism suspects.

Staff Sgt. Miguel Fabbiani, a friend of Alford's and a member of the same team based at Fort Campbell, said Alford's symptoms escalated during wartime when he was working with a new group that didn't know him as well.

Alford's parents said they didn't see him enough to detect a problem. His wife was stationed near him for a while in Kuwait, but she chalked up his odd behavior to stress.

Alford's father said the actions of his son's superiors broke the spirit of a young man who had wanted to become a soldier since he was 4.

He now lies in pastel sheets next to a wall painting of John Wayne. Wearing a Houston Texans T-shirt that hangs like a hospital gown, he stares absently into a television that glows 24 hours, his hands gripping stuffed animals to keep them from clenching shut.

"He knows his name, sometimes," says his wife, a tiny woman in sneakers who helps tend to her husband as she ponders a life alone. "Sometimes I'll go up to him, wink at him and make kissy faces, and he laughs."

Her eyes well up as she remembers the handsome, arrogant boy she met as a teen-ager at a barrel-racing contest in Texas.

As his brain deteriorates, his organs will fail.

"He will go blind, he will go deaf, he will lose everything," his father said.

He stopped walking more than a month ago, mumbles when he tries to speak, is fed intravenously and takes medicine for insomnia, pain and tremors. Doctors have told the family that he probably won't live to see Christmas.

The Army has said that the issues over Alford's pay could be resolved within weeks, but the family members are skeptical. They aren't sure how they will pay his bills and maintain his 24-hour care without his salary.

"It's very sad when the people who are putting their life on the line for this country should be treated like this," Alford's father said. "This has been a bureaucratic nightmare. We've got enough to deal with on a daily basis, caring after our son and dealing with our pain and weariness and our suffering to have to fight the U.S. Army."

They fought for four months before his rank was reinstated in September.

John Alford knew his son might not live long enough to get the good news, so he had already told him a "white lie" that he had been vindicated.

"It was very important to him because he kept saying, 'I didn't do anything wrong, Daddy.' "

http://sierratimes.com/03/11/23/ap_gi_battle.htm

12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie A] The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6



http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf



1: J Infect Dis 1980 Aug;142(2):205-8



Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

PMID: 6997404


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract



[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine
Spongiform Encephalopathy (BSE)


http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf



[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle

03-025IFA
03-025IFA-2


http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf



THE SEVEN SCIENTIST REPORT ***


http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf




Terry S. Singeltary Sr.

P.O. Box 42

Bacliff, Texas USA 77518




http://www.blackfive.net/main/2004/10/a_dying_hero_ss.html



http://www.blackfive.net/main/2004/03/ssg_james_alfor.html



http://brain.hastypastry.net/forums/archive/index.php/t-3238.html



His commander wrote on April 10 that he would initiate action to revoke Staff Sgt. Alford's Special Forces designation.

Critical comments

"Your conduct is inconsistent with the integrity and professionalism required by a Special Forces soldier," wrote Lt. Col. Christopher E. Conner of the 2nd Battalion, 5th Special Forces Group Headquarters in Kuwait. "I do not believe you are suitable for further Special Forces duty." The Alfords were later told that Staff Sgt. Alford had been seen by a doctor in Kuwait, who reportedly said nothing was wrong with him. A psychiatrist in Kuwait reportedly said that he was "faking it."

"Jamie was a good soldier," said his mother, who has left her job to care for her son. "When all this started happening, anyone should have known he was sick."

The cause of Staff Sgt. Alford's disease, diagnosed as "sporadic" CJD, is unknown.



http://www.valdezlink.com/pages/alford.htm



Bovine Spongiform Encephalopathy and variant Creutzfeldt-Jakob Disease Questions and Answers 9 March 2001



5. Of the reported vCJD fatalities, were any of them U.S. Service Members? No. There are no reported cases of vCJD in the US, including service members and their families wherever they are stationed.



snip...



3. What was the source of beef consumed by military personnel stationed in Europe? For service members stationed in Europe prior to 1996, beef sources were: a) Dining Facilities: U.S. beef has been served in all military dining facilities since before 1980. b) Operational rations: In MRE’s, T rations, UGRs, field feeding and all other operational rations only US beef was used. c) Commissaries: Prior to 1990, commissaries in Europe procured approximately 35% of the beef from the UK and 65% from other European countries. Since 1990, commissaries in Germany, Netherlands, Belgium and the UK (excluding Edsal commissary in Scotland) received only US beef. Commissaries in Italy, Spain, Greece, and Turkey (and the Edsal commissary in Scotland) continued getting the majority of their beef from the UK until 1996 when all procurement of beef from the UK ended. d) Army and Air Force Exchange Service (AAFES): European beef was used up until 2000. Approximately 20% of this was from the UK until March 1996. In March 1996, DoD stopped procurement and sale of beef from the UK and other countries with confirmed cases of BSE. Since March 2000, DoD stopped procurement and sale of ruminant (e.g., cattle, sheep, and goat) meat and meat products of European origin. The procurement of these meat items is now required to be from US and non-European approved sources. 4. What was the source of beef consumed by military personnel stationed overseas in areas other than Europe? The possibility exists for UK or other European beef to have been consumed in areas outside of Europe. For example, it may have been purchased by naval ships resupplying in the Mediterranean, or provided to service members in SW Asia following Operations Desert Shield/Desert Storm. From 1990 to March 1996, military dining facilities in Southwest Asia utilized beef originating from several countries, including the UK. DoD policy excluded UK beef after March 1996 and European beef after March 2000.



http://chppm-www.apgea.army.mil/MadCowDisease/QA.pdf



THE QUESTION SHOULD HAVE BEEN, Of the reported CJD fatalities, were any of them U.S. Service Members? FOR THE FOLLOWING REASONS ; "the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine."


http://bse-atypical.blogspot.com/2008/08/atypical-bse-base-transmitted-from.html



Guidance for Industry Questions and Answers on FDA Guidance Entitled "Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob (CJD) Disease and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products"



Updated January 22, 2004



http://www.fda.gov/Cber/gdlns/cjdvcjdq&a.htm



Emerging and Re-emerging Infectious Diseases CME
Disclosures

John G. Bartlett, MD



snip...

Variant Creutzfeldt-Jakob disease

Variant Creutzfeldt-Jakob disease (vCJD) was included in the literature review by John Bartlett, citing evidence of transmission by blood transfusion of the prion protein (PrP) in England.[4,5] This case strongly supports the hypothesis that blood and blood components, presumably leukocytes, can transmit this universally fatal disease. The initial report was followed by a second case, which was quite different in several ways.[6] This patient was discovered because a look-back suggested a possible acquisition of PrP from a blood donation of a patient who subsequently died of vCJD. However, the recipient was heterozygote at codon 129 of the PrP gene and died of a ruptured aneurysm with no clinical evidence of vCJD. The PrP was detected in a lymph node and the spleen, indicating that the pool of infected patients may not be restricted to those who are homozygote at codon 129. (All cases of vCJD to date have been homozygote with M/M at codon 129 of the prion gene).

US Food and Drug Administration looks at transfusion practices. To bring this issue up-to-date, the relevance of these data for transfusion practices was reviewed in US Food and Drug Administration (FDA) hearings in October 2004. The network of look-backs (ie, patients warned of possible transfusion-associated vCJD) has now been expanded to about 6000 persons in England. Also, there is concern about a possible resurgence of long-incubation cases in patients who are heterozygote at codon 129. Against this background, Gary Roselle reported the results of an intensive look-back of potential transmission of CJD in the Veterans Affairs (VA system).[7] The cases involved a donor who had donated over 10 gal prior to developing CJD (not vCJD). These donations were divided into over 200 lots and given to thousands of recipients. A decision was made to not conduct a look-back because there was no evidence that CJD could be transmitted by blood or blood products, but the VA made a different decision. There were 1615 recipients of blood and blood products from this single donor who were patients at 68 VA sites. Look-backs in 429 persons who are still living failed to show any evidence of transmitted CJD. Discussion with the presenter indicated minimal difficulties encountered with the notification of patients of this possible complication of their prior transfusions.



http://www.medscape.com/viewarticle/499461



From: Terry S. Singeltary Sr.

To: FREAS@CBER.FDA.GOV

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

Sent: Friday, December 01, 2006 2:59 PM

Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION

snip...

ONE FINAL COMMENT PLEASE, (i know this is long Dr. Freas but please bear with me)

THE USA is in a most unique situation, one of unknown circumstances with human and animal TSE. THE USA has the most documented TSE in different species to date, with substrains growing in those species (BSE/BASE in cattle and CWD in deer and elk, there is evidence here with different strains), and we know that sheep scrapie has over 20 strains of the typical scrapie with atypical scrapie documented and also BSE is very likely to have passed to sheep. all of which have been rendered and fed back to animals for human and animal consumption, a frightening scenario. WE do not know the outcome, and to play with human life around the globe with the very likely TSE tainted blood from the USA, in my opinion is like playing Russian roulette, of long duration, with potential long and enduring consequences, of which once done, cannot be undone.

These are the facts as i have come to know through daily and extensive research of TSE over 9 years, since 12/14/97. I do not pretend to have all the answers, but i do know to continue to believe in the ukbsenvcjd only theory of transmission to humans of only this one strain from only this one TSE from only this one part of the globe, will only lead to further failures, and needless exposure to humans from all strains of TSE, and possibly many more needless deaths from TSE via a multitude of proven routes and sources via many studies with primates and rodents and other species. ...

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

snip... 48 pages...

http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8



4th case of variant CJD infection associated with blood transfusion 18 January 2007

A new case of variant-Creutzfeldt-Jakob disease (vCJD ) associated with a blood transfusion has recently been diagnosed.

This latest patient has been diagnosed with vCJD about nine years after receiving a blood transfusion from a donor who later went on to develop vCJD. A transfusion from the same blood donor was also associated with one of the previously identified cases. The patient is still alive and is under specialist care.

This fourth case of vCJD infection associated with blood transfusion increases the concern about the risk of vCJD transmission between humans via blood transfusion. All four cases relate to the transfusion of blood components: no cases have been reported relating to treatment with plasma products.

The patient is one of a small number (less than 30) of living individuals who are known to have received a blood transfusion in the UK from a donor who later developed vCJD. All these individuals have previously been informed of their potential exposure to vCJD and asked to take certain precautions to reduce the chance of passing on vCJD to other people via healthcare procedures, such as surgery.

The Health Protection Agency has been in contact with doctors caring for the other patients who have been exposed to blood transfusions from donors who later developed vCJD. This is to ensure that they are informed of this new development and provide access to the latest information and specialist advice about their risk due to blood transfusion.

Professor Peter Borriello, Director of the HPA's Centre for Infections said, "This new case of vCJD infection increases our concern about the risk to the small group of people who had blood transfusions from donors who unknowingly at the time of donation must have had vCJD infection. However, this new case does not change our understanding of the risk for other people in any specific way. It does however reinforce the importance of the precautions that have already been taken to reduce the risk of transmission of vCJD infection by blood."

Dr Angela Robinson, Medical Director of NHS Blood and Transplant said, "Blood transfusions are often given to save or prolong the life of patients who are very ill and the benefit of receiving a transfusion when needed must always be balanced against any possible risk. Nonetheless, our primary concern is the safety of our patients through maintaining the quality of blood used for medical treatment. Since 1997, the NBS has introduced a range of precautionary measures against the risk of vCJD."

vCJD is a rare disease, and less than 2% of the vCJD cases reported to date in the UK have been associated with blood transfusion.

Notes to Editors:

To date, there have been 66 people identified in the UK who have received vCJD implicated blood transfusions. The transfusions received by these 66 individuals were donated by eighteen different donors who were diagnosed with vCJD after their blood donation. Of these 66 people, 40 have died of illnesses other than vCJD, including one patient who was found to have evidence of vCJD in parts of their body after their death. Including the new (4th) case, 3 of these people who have received vCJD implicated blood transfusions have developed symptoms of vCJD. There are 23 people who have received vCJD implicated blood transfusions who are alive and have not been diagnosed with vCJD.

The identification of cases of variant-CJD associated with blood transfusion has depended on the Transfusion Medicine Epidemiology Review, a collaborative study between the National Blood Services, the National CJD Surveillance Unit and the Office of National Statistics. For further information about this study see Hewitt et al Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Epidemiology Review study. Vox Sanguinis 2006 91:221-230.

'Blood Transfusion' means transfusion with labile blood components (e.g. red cells, platelets, fresh frozen plasma). This latest case (and the previous three referred to) relate to transfusion of blood components and not treatment with plasma products (i.e. products that are manufactured from plasma). To date, no case of vCJD has been associated with treatment with plasma-products (e.g. clotting factors used to treat individuals with bleeding disorders such as haemophilia).

This fourth case has been classified by the National CJD Surveillance Unit ( www.cjd.ed.ac.uk ) as a 'probable' case of vCJD. Of the 158 vCJD cases that have died (data to 5 Jan 2007), all 112 that have undergone post-mortem (46 have not) have been 'confirmed' by neuropathological examination (examination of brain tissue).

The first clinical case of vCJD associated with transfusion was identified in December 2003. A case of vCJD 'infection' associated with transfusion was identified a few months later. The patient had no symptoms but evidence of infection (abnormal prion proteins) was identified in a post mortem investigation. The individual died from causes unrelated to vCJD.

Following the first case of vCJD associated with a blood transfusion in 2003, the Department of Health asked all recipients of blood transfusions not to donate blood as a precautionary measure to protect the blood supply from vCJD.

Patients who are informed that they are considered to be 'at risk' of vCJD for public health purposes are asked to take the following precautions to reduce the chance of passing on vCJD to other people: Not to donate blood, tissues or organs and To inform their healthcare providers of their 'at-risk' status so that special procedures may be arranged for certain instruments used in their healthcare (NB. Their GPs are also asked to do this.)

A range of measures have been put in place by the Department of Health to minimise the possible risk of vCJD being passed through blood:

Since 1997 all cases of vCJD that are reported to the National CJD Surveillance Unit and diagnosed as having 'probable' vCJD, result in a search of the UK Blood Services blood donor records. If the patient has donated blood, any unused parts of that blood are immediately removed from stock. The fate of all used components of blood from the donor is traced, and surviving recipients informed of their risk. In July 1998, the Department of Health announced that plasma for the manufacture of blood products, such as clotting factors, would be obtained from non-UK sources. Since October 1999, white blood cells (which may carry the greatest risk of transmitting vCJD) have been removed from all blood used for transfusion. In August 2002 the Department of Health announced that fresh frozen plasma for treating babies and young children born after 1 January 1996 would be obtained from the USA, extended to all children under 16 years of age (Summer 2005). In December 2002, the Department of Health completed its purchase of the largest remaining independent US plasma collector, Life Resources Incorporated. This secures long-term supplies of non-UK blood plasma for the benefit of NHS patients. Since April 2004, blood donations have not been accepted from people who have themselves received a blood transfusion in the UK since 1980. This has been extended to include apheresis donors and donors who are unsure if they had previously had a blood transfusion (August 2004). Since late 2005, blood donations have not been accepted from donors whose blood was transfused to patients who later developed vCJD. The UK Blood Services continue to promote the appropriate use of blood and tissues and alternatives throughout the NHS.

The likelihood of a person who may be infected with vCJD going onto develop symptoms of the disease is uncertain, and may depend on individual susceptibility. It is possible that infected individuals may never develop symptoms.

For further information contact the HPA press office on 0208 327 7098/7097/6055

Specialist care for vCJD is available from The NHS National Prion Clinic, based at The Hospital for Neurology and Neurosurgery, Queen Square, London http://www.nationalprionclinic.org/

The National CJD Surveillance Unit is based at the Western General Hospital Edinburgh: www.cjd.ed.ac.uk

For further information about vCJD go to:

http://www.hpa.org.uk/infections/topics_az/cjd/menu.htm

http://www.dh.gov.uk/PolicyAndGuidance/HealthAndSocialCareTopics/CJD/fs/en

http://www.blood.co.uk/ http://www.cjd.ed.ac.uk http://www.nationalprionclinic.org/

Last reviewed: 13 December 2007



http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1195733711457?p=1171991026241



TRANSFUSION MEDICINE

EPIDEMIOLOGY REVIEW (TMER)

The Transfusion Medicine Epidemiology Review (TMER) is a collaborative project between the UK NCJDSU and the UK Blood Services. The main purpose is to investigate whether there is any evidence that Creutzfeldt-Jakob disease (CJD) or variant Creutzfeldt-Jakob disease (vCJD) may have been transmitted via the blood supply.

This website contains data on vCJD donors and cases of vCJD who have received transfusions in the past but does not contain data on the ongoing study of sporadic CJD.

This site was last updated on 11 March 2008

Methods

Results

vCJD donor summary

Use of blood donations from vCJD cases

Fate of recipients

vCJD cases who received blood tranfusion(s) in the past

Relevant Publications

Back to NCJDSU Home Page

http://www.cjd.ed.ac.uk/TMER/TMER.htm




Thursday, July 24, 2008

Prion diseases are efficiently transmitted by blood transfusion in sheep


http://vcjdblood.blogspot.com/2008/07/prion-diseases-are-efficiently.html




4th CASE VCJD VIA BLOOD TRANSFUSION, BSE, BASE, AND SPORADIC CJD

By Terry S Singeltary

Bacliff, Texas USA Jan 24, 07

http://www.bloodindex.com/view_news_zone.php?id=206



Subject: Re: Docket No. 2005N-0373 RIN number 0910-AF54 Use of Materials Derived From Cattle in Medical Products REOPENING COMMENT PERIOD Date: March 30, 2007 at 11:37 am PST

Subject: Re: Docket No. 2005N-0373 RIN number 0910-AF54 TSS SUBMISSION Date: March 30, 2007 at 10:57 am PST


http://madcowfeed.blogspot.com/2008/07/docket-no-2005n-0373-and-rin-number.html



18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7 December 2006 are now available.

snip...

4. Members had received information about the notification by the Health Protection Agency (HPA) of recipients of four batches of plasma products that had been produced from blood donated by individuals that had later developed variant Creutzfeldt Jakob Disease (vCJD). THESE batches HAD NOT been included in a similar notification exercise in 2004, as the fate of these products COULD NOT BE TRACED at that time. The fourteenth annual report of the National CJD Surveillance Unit had been published. The European Food Safety Authority (EFSA) had issued a consultation on a revised methodology for geographical bovine spongiform encephalopathy (BSE) risk assessment. Members could submit individual responses. Submission of a SEAC response was under consideration.

snip...

ITEM 9 - ANY OTHER BUSINESS

snip...

***$$$***

64. A member noted that at the recent Neuroprion meeting, a study was presented showing that in transgenic mice BSE passaged in sheep may be more virulent and infectious to a wider range of species than bovine derived BSE. Other work presented suggested that BSE and bovine amyloidotic spongiform encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A MUTATION FOUND IN CASES OF SPORADIC CJD. A study also demonstrated that in a mouse model it was possible to alleviate the pathological changes of prion disease by suppressing expression of the prion protein gene after infection.

http://www.seac.gov.uk/minutes/95.pdf



Molecular Mechanisms of Prion Pathogenesis

Adriano Aguzzi, Christina Sigurdson, and Mathias Heikenwaelder Institute of Neuropathology, University Hospital of Z¨ urich, CH-8091 Z¨ urich, Switzerland; email: adriano.aguzzi@usz.ch, mathias.heikenwaelder@usz.ch, christina.sigurdson@usz.ch Annu. Rev. Pathol. Mech. Dis. 2008. 3:11–40 First published online as a Review in Advance on August 8, 2007 The Annual Review of Pathology: Mechanisms of Disease is online at pathmechdis.annualreviews.org This article’s doi: 10.1146/annurev.pathmechdis.3.121806.154326 Copyright c 2008 by Annual Reviews. All rights

Annu. Rev. Pathol. Mech. Dis. 2008. 3:11–40 First published online as a Review in Advance on August 8, 2007 The Annual Review of Pathology: Mechanisms of Disease is online at pathmechdis.annualreviews.org This article’s doi: 10.1146/annurev.pathmechdis.3.121806.154326 Copyright c 2008 by Annual Reviews. All rights reserved 1553-4006/08/0228-0011$20.00



Abstract



Prion diseases are infectious neurodegenerative diseases occurring in humans and animals with an invariably lethal outcome. One fundamental mechanistic event in prion diseases is the aggregation of aberrantly folded prion protein into large amyloid plaques and fibrous structures associated with neurodegeneration. The cellular prion protein (PrPC) is absolutely required for disease development, and prion knockout mice are not susceptible to prion disease. Prions accumulate not only in the central nervous system but also in lymphoid organs, as shown for new variant and sporadic Creutzfeldt- Jakob patients and for some animals. To date it is largely accepted that prions consist primarily of PrPSc, a misfolded and aggregated â-sheet-rich isoform of PrPC. However, PrPSc may or may not be completely congruent with the infectious moiety. Here, we discuss the molecular mechanisms leading to neurodegeneration, the role of the immune system in prion pathogenesis, and the existence of prion strains that appear to have different tropisms and biochemical characteristics.



snip...



As an example in the field of human medicine, four cases of vCJD have been reported to be caused by blood transfusion (9– 11). This indicates that BSE prions can be recycled among humans, which has caused considerable alarm that the supply of bloodderived pharmaceuticals may be threatened (12). In particular, the report of a subclinical blood-derived vCJD infection in an individual carrying a heterozygote methionine/ valine polymorphism at codon 129 of the human PRNP gene (10) suggests that transmission of BSE prions to humans enhances their virulence and broadens the spectrum of susceptible recipients. In this respect, it has been demonstrated that polymorphisms at codon 129 of the human PRNP gene control susceptibility and incubation time in human patients (e.g., 129MM versus 129MV or 129VV drastically increases the susceptibility of humans to BSE prions). It was reported only recently that most individuals who suffered from kuru and were polymorphic at codon 129 showed incubation times longer than 50 years (13). Moreover, recent reports indicate that there is still a lot to be learned about the mechanisms of prion transmission (e.g., human to human or within scrapie-affected animal flocks) and prion tropism underlining the complex alternating distribution patterns of PrPSc (e.g., PrPSc deposition in lymphoid tissue, the CNS) and prion infectivity under varying conditions (e.g., chronic inflammation) and hosts (e.g., sheep, elk and deer, human): Chronic inflammation can alter the tropism of prion infectivity or PrPSc to organs hitherto believed prion free (e.g., liver, pancreas, kidney of mice, mammary gland of sheep, muscle of humans) (14–16). Moreover, PrPSc was reported in spleen and muscle tissue of sporadic Creutzfeldt-Jakob disease (sCJD) patients (17), and prion infectivity was demonstrated in muscle, blood, and saliva of deer suffering from CWD (18, 189). Also, prion infectivity was shown to be excreted via urine of prion-infected nephritic mice, a process defined as prionuria (19). These results emphasize the need for further assessment of possible public health risks from TSE-affected extraneural organs. It is very well possible that preexisting pathophysiological conditions of the infected host additionally contributed to unexpected distribution patterns of prion infectivity. For example, the presence of prion infectivity in the blood of sheep or deer may influence the deposition of prion infectivity in various organs previously deemed prion free. Therefore, it should be carefully reconsidered whether only organs of the CNS and the lymphoreticular system should be included in the current risk classifications of biologicals in the future. It will be important to test altered prion tropism profiles in nonlymphoid organs and body fluids (e.g., blood, urine, milk, saliva) of ruminants (e.g., sheep, goat, cattle, elk, and deer) and human patients suffering from sCJD and vCJD.



snip...



Recent in vivo evidence indicated that a similar phenomenon of conformational variants may occur in Alzheimer’s disease (151). Here the existence of Aâ strains that can seed and accelerate aggregation and Aâ pathology was posited. These intriguing observations support the hypothesis that the pathogenetic mechanisms operating in Alzheimer’s disease and in prion diseases have more in common than we often appreciate (152). Perhaps future studies will address whether different Aâ strains with distinct biochemical or neuropathological characteristics occur in humans. Can multiple prion strains coexist and effect prion replication? Two subtypes of sporadic CJD have recently been demonstrated to coexist in humans (62). Experimental studies have shown that when two strains infect the same host, one strain can impede the ability of the second strain to cause disease (153). Bartz and colleagues (154) recently suggested that this might be caused by the suppression of prion replication of the second strain. Strain features are useful for tracing prion infections between species. When transmitted to primates, BSE causes lesions strikingly similar to that of vCJD (155, 156). BSE is most likely transmissible to humans too, and strong circumstantial evidence (157–159) suggests that BSE is the cause of vCJD, which has claimed more than 200 lives in the United Kingdom (3, 160), as well as a much smaller number in some other countries (161).

NATURAL TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: WHAT IS NEW? Cattle Prions More than a few surprises have come from further investigations of prion strains in field cases of TSEs. Until recently, BSE was believed to be associated with one single prion strain, classified by an exclusive and remarkably stable biochemical profile of PrPSc. However, distinct molecular signatures have recently been discovered through the large-scale screening of cattle mandated by European authorities in the context of BSE surveillance. These atypical profiles fall into either of two groups: H-type cases of protease-resistant fragments with a molecular weight higher than BSE, and bovine amyloidotic spongiform encephalopathy, or L type (lower) (162). To test whether these different biochemical and histopathological properties correspond to distinct strains, the Laude laboratory transmitted H-type-PrPSc isolates from French cattle into transgenic mice expressing bovine or ovine PrP (163). The recipient mice developed neurological signs exhibiting strain-specific features clearly distinct from that of the classical BSE agent, providing pivotal evidence that the underlying strains are distinct.



Atypical Sheep Scrapie In 1998, aberrant cases of sheep scrapie were described in Norway and the strain was newly classified as Nor98 (164). Active European Union surveillance later revealed additional cases of atypical scrapie in several other countries (165, 166). Sheep infected with Nor98, or atypical scrapie, accumulated PrPSc primarily in the cerebellum and cerebral cortex rather than in the brainstem target in the classical strain (167). Additionally, on western blot analysis of atypical scrapie cases, an additional small-molecular-weight (10–12 kDa) PrP fragment appeared afterPKdigestion and was shown by epitope mapping to lack both N and C termini of PrP (167, 168). Furthermore, atypical scrapie cases occurred not only in the classical scrapie-susceptible genotypes (A136 R154 Q171), but also in genotypes associated with high resistance to classical scrapie (A136 R154 R171) (165, 166). Were these atypical scrapie cases also infectious? In 2001, atypical scrapie cases were shown to be transmissible prion diseases after inoculated ovine PrP-expressing transgenic mice developed disease and prion aggregates (169). In the meantime, several countries appear to be reporting extremely high incidences of atypical scrapie, and in fact atypical scrapie appears to be the rule rather than the exception in some geographical areas.


Chronic Wasting Disease Among all animal prion diseases, CWD of cervids is likely the most efficiently transmitted. CWD infections occur in mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), Rocky Mountain elk (Cervus elaphus nelsoni) (170), and moose (Alces alces shirasi) (171). Prevalence can reach as high as 30% in dense, free-ranging deer populations and nearly 100% in captive animals (171). Hypotheses for CWD transmission range from spread via direct contact to exposure through grazing in areas contaminated by prion-infected secretions, excretions (saliva, urine, feces), tissues (placenta), or decomposed carcasses. Insightful experimental studies have recently revealed two key findings: (a) Saliva from CWD-infected deer can transmit disease (18), and (b) CWD-infected carcasses allowed to decay naturally in confined pastures can lead to CWD infections in captive deer (172). Additionally, the abundant CWD-prion accumulation within lymphoid tissues may also lead to CWD prion buildup in nonlymphoid organs with lymphoid follicles, as was recently shown in kidney, potentially shifting shedding routes (173). It is unknown whether other types of inflammation, such as the granulomatous inflammation in the intestine seen in Johne’s disease (Mycobacterium avium subsp. paratuberculosis; affects ruminants, including deer and elk) or parasitic inflammation, could lead to or perhaps increase prion excretion by fecal routes. The environmental prion contamination in CWD underscores the difficulties of CWD disease management.Within North America,CWDinfected deer and elk have been detected in 14 states and two Canadian provinces (170, 174, 175). CWD surveillance in Europe has been more limited. However, in Germany, a total of 7300 captive and free-ranging cervids were tested forCWDwith no sign of infection (176). Reindeer or caribou (Rangifer tarandus), from North America or Northern Europe respectively, have a highly homologous prion sequence compared with mule deer and thus are likely susceptible to CWD. Other European cervids such as moose and red deer (C. elaphus) are also expected to be CWD susceptible. The deer and elk primary protein structures are highly conserved, as seen in other mammals. Interestingly, a polymorphism at codon 225S/F may influence CWD susceptibility in mule deer. When comparing the frequency of genotypes among CWDnegative and -positive deer (n = 1482), the odds that a CWD-infected animal was 225SS was 30 times greater when compared with 225SF, whereas the frequency of 225SF/FF genotypes in CWD-negative deer was 9.3%, but only 0.3% in CWD-positive deer (177).



Additionally, elk have a polymorphism at codon 132 (M/L) of Prnp, corresponding to polymorphic codon 129 (M/V) in humans. Elk expressing 132ML and 132LL Prnp were reported to be overrepresented among elk with CWD when compared with uninfected controls (178), and 132LL elk experimentally infected with CWD have resisted infection for at least four years, whereas 132MM or 132ML elk (n = 2 each) developed terminal clinical prion disease by 23 or 40 months post inoculation, respectively, confirmed by immunohistochemistry and western blotting for PrPSc (179). White-tailed deer also have Prnp polymorphisms that may affect their CWD susceptibility. A reduced susceptibility to CWD was linked to a G96S and a Q95H polymorphism in a study comparing allelic frequencies from CWD-positive and CWDnegative free-rangingWisconsin white-tailed deer (180).



snip...end



http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.pathmechdis.3.121806.154326



USA PRION UNIT BLOG

http://prionunitusaupdate2008.blogspot.com/



Sunday, April 20, 2008 Progress Report from the National Prion Disease Pathology Surveillance Center April 3, 2008

Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.

see full text ;

http://prionunitusaupdate2008.blogspot.com/2008/04/progress-report-from-national-prion.html



CJD TEXAS (cjd clusters)

http://cjdtexas.blogspot.com/



USA WRITTEN CJD QUESTIONNAIRE ???

http://cjdquestionnaire.blogspot.com/



The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.

http://www.cjdfoundation.org/fact.html



>>>"the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine." <<< href="http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v07232.pdf">http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v07232.pdf< /a>



please see full text ;

http://bse-atypical.blogspot.com/2008/06/review-on-epidemiology-and-dynamics-of.html



***Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.***

Progress Report from the National Prion Disease Pathology Surveillance Center

An Update from Stephen M. Sergay, MB, BCh & Pierluigi Gambetti, MD

April 3, 2008

http://www.aan.com/news/?event=read&article_id=4397&page=72.45.45



Sunday, March 16, 2008

MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE

http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html



HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008

snip...

Tissue infectivity and strain typing of the many variants Manuscript of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...

snip...

http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html



Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate


http://organicconsumers.org/forum/index.php?showtopic=1951

http://bse-atypical.blogspot.com/2008/08/atypical-bse-base-transmitted-from.html



Thursday, July 10, 2008

A New Prionopathy


http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html



Sunday, August 10, 2008

A New Prionopathy OR more of the same old BSe and sporadic CJD

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html



Wednesday, August 20, 2008


Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ?


http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html


UPDATE AUGUST 28, 2008


LETTER TO EDTOR: Care over research

Tuesday, August 26, 2008 Comment Print Listen Font Size Share Ask a Question You Report I, and every reader, can feel the pain and anguish of the family chronicled in The Times article "Hospital released vet who refused study" (Page 1, Friday). The disease mentioned, Creutzfeldt-Jakob disease, is devastating, unremitting and, as yet, without cure.

It is also difficult to sort out from other diseases with similar symptoms. Medicine does not know why it progresses more quickly in some people than in others. It is for these reasons that medical research is done - to understand better how to improve the chances of the next veteran who has such a problem.

In this case, a National Institutes of Health (NIH) study in which the Department of Veterans Affairs partnered with Mount Sinai Hospital, a world renowned academic medical center, was offered to the patient. The study was designed, as noted, to observe and to learn more about "conditions affecting memory or thinking, including Alzheimer's disease and related disorders." The research was to study the progression of disease, not to offer an experimental treatment. The study's consent form even states that "this study is not designed to benefit participants."

I can only apologize that Aimee Fitzgerald perceived a sense of callousness or a sense that there were some additional diagnostic or other measures to be offered as she sought answers to unanswerable questions about her ailing husband, Joe. It will renew our emphasis to VA staff about sensitivity in communicating. I and the VA completely share the view of bioethicist Arthur Caplan that the goal of the medical encounter must be first and foremost to provide the latest and best care when care is available, that research must take a secondary role to receiving patient care and that no one should be penalized for failing to volunteer for a study, ever.

It is the VA's policy - clearly stated in our regulations, directives, patient literature and the protocol consent form - that a patient has a right to say no to participating in a research study and that decision will not affect the VA health care or benefits the patient receives.

In serving our veterans, we have an absolute obligation to provide not only the highest quality care and to provide that care with attention and compassion, but to find better ways to care for our patients through research with the highest scientific and ethical standards. It is what we strive for every single day across our system. I can only apologize for the family's perception in this tragic case and to let them know that it will serve as a systemwide reminder about the importance of clear and compassionate communication.

DR. JAMES B. PEAKE

Secretary of veterans affairs

Washington

http://washingtontimes.com/news/2008/aug/26/care-over-research/


VA chief offers family apology Vet died after refusing research Audrey Hudson (Contact) Tuesday, August 26, 2008

The secretary of the Department of Veterans Affairs has apologized to the family of an Army veteran who died last year after being turned away from a Bronx VA hospital after he refused to participate in an Alzheimer's disease study.

Joe Fitzgerald, 74, died of Creutzfeldt-Jakob disease - the human form of mad cow disease - less than a month after being dismissed without diagnosis or treatment at James J. Peters VA Medical Center, The Washington Times reported Friday.

His widow, Aimee Fitzgerald, has demanded answers from the VA as to whether human research testing is taking a priority over the health care of veterans after the agency responded that the Alzheimer's study was a "mandate."

"I can only apologize that Mrs. Fitzgerald perceived a sense of callousness, or a sense that there was some additional diagnostic or other measures to be offered," Veterans Affairs Secretary James B. Peake said in a letter to the editor at The Times. "It will renew our emphasis to VA staff about sensitivity in communicating."

The VA has come under scrutiny and criticism over its human-subject experiments since a Washington Times/ABC News investigation revealed in July that the agency had failed to quickly notify participants in a smoking-cessation study about the potentially dangerous side effects of a drug some participants were taking.

A recent investigation of experiments conducted at an Arkansas veterans hospital uncovered rampant violations, including missing consent forms, secret HIV testing and failure to report more than 100 deaths of subjects participating in studies.

Mr. Fitzgerald sought treatment for his sudden loss of motor skills at the Bronx VA hospital when his attending physician, Dr. Ruth Walker, said that enrolling in the Alzheimer's study would enable a quicker diagnosis of his disease, Mrs. Fitzgerald said.

Dr. Walker introduced the family to Dr. Christine Bergmann, who headed the Alzheimer's study. VA officials said Dr. Bergmann did not have the authority to offer a diagnosis.

"I can only apologize for the family's perception in this tragic case and to let them know that it will serve as a system-wide reminder about the importance of clear and compassionate communication," Mr. Peake said in his letter to the editor.

The Times also reported that Arthur Caplan, one of the nation's premier medical ethicists and director of the Center for Bioethics at the University of Pennsylvania, said the first obligation of any caregiver is to treat the patient.

In his letter, Mr. Peake - a physician himself - said he and his agency "completely share Mr. Caplan's view."

http://washingtontimes.com/news/2008/aug/26/va-chief-offers-family-apology/



Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

Labels: , , ,

Wednesday, August 20, 2008

Tonometer disinfection practice in the United Kingdom: A national survey

Eye (2008) 22, 1029–1033; doi:10.1038/sj.eye.6702831; published online 20 April 2007

Tonometer disinfection practice in the United Kingdom: A national survey
Financial or proprietary interest: nil

Financial Support: nil

R J Hillier1 and N Kumar1

1Ophthalmology Department, Aintree University Hospitals NHS Foundation Trust, Walton Hospital, Liverpool, UK

Correspondence: RJ Hillier, SpR in Ophthalmology, Manchester Royal Eye Hospital, Oxford Road, Manchester M13 9WH, UK. Tel: +44 07811 190588; Fax: +44 0161 276 5555; E-mail: roxanehillier@doctors.org.uk

Received 2 October 2006; Revised 16 March 2007; Accepted 16 March 2007; Published online 20 April 2007.

Top of page
Abstract
Purpose:

To assess current tonometer disinfection practice in the UK, and compare with published recommendations.

Methods:

Every ophthalmology unit with training recognition in the UK was contacted (n=155). A senior nurse at each institution completed a telephone questionnaire regarding local tonometer disinfection practice.

Results:

The response rate was 100%. Thirty-five units (23%) reported exclusive use of disposable tonometer heads and were excluded from further analysis. One hundred and twenty units (77%) used either reusable or a combination of reusable and disposable tonometer heads. Where reusable heads were used, 80 units (67%) immersed them in a chlorine-based solution such as sodium hypochlorite or sodium dichloroisocyanurate. Others used isopropyl alcohol (18 units), hydrogen peroxide (12 units), chloramine (5 units), chlorhexidine (4 units) and peracetic acid (1 unit). Where a chlorine-based agent was used, the concentration of available chlorine ranged from 125 to 30 000 p.p.m., with 50 units (63%) using a concentration of less than 5 000 p.p.m. (i.e., inadequate based on published recommendations). Where the tonometer head was immersed in disinfectant between patients (n=101), 29 units (29%) provided just one tonometer head per practitioner, making adequate soak time between patients unlikely. Every unit replenished the disinfectant at least daily, deemed sufficient for most agents. However, hydrogen peroxide solutions should be replenished twice daily, which did not take place in nine units.

Conclusion:

This survey reveals disparity between current tonometer disinfection practice and published international recommendations, with some institutions using practices that may render patients susceptible to transmissible infection.

Keywords:
disinfection, tonometry, glaucoma



http://www.nature.com/eye/journal/v22/n8/abs/6702831a.html



PA-34

SPORADIC CREUTZFELDT-JAKOB DISEASE: PRPRES IS CONSTANTLY PRESENT IN THE RETINA, AND RARELY IN THE OPTIC NERVE

M. Mangieri1, G. Giaccone1, L. Limido1, G. Di Fede1, S. Suardi1, R. Capobianco1, P. Fociani2, O. Bugiani1, F. Tagliavini1 1 Istituto Nazionale Neurologico Carlo Besta, Division of Neuropathology and Neurology 5, Milano, Italy and 2 Ospedale Luigi Sacco, Division of Pathology, Università di Milano, Milano, Italy

e-mail: mmangieri@istituto-besta.it

Creutzfeldt-Jakob disease (CJD) is marked by the presence of the protease-resistant prion protein (PrPres) in the brain. Studies of the retina and optic nerve in patients with CJD are scanty and on very small series of patients. We analysed ocular tissues of sporadic CJD patients (retina of 58 and optic nerve of 51), representing all combinations of PRNP codon 129 polymorphisms and PrPres types by Parchi, except VV1. Ocular tissue from 24 patients with other neurological diseases were used as controls. The ocular tissue was collected at autopsy and the samples were fixed in Carnoy solution or frozen. Before immunohistochemistry with 3F4 antibody, the sections were pretreated with proteinase K and guanidine thiocyanate. In all cases of sCJD the retina showed immunoreactivity for PrPres localized in the inner and outer plexiform layers, with a synaptic type of labelling. No difference in the pattern of labeling was detected between CJD patients with different PRNP codon 129 polymorphisms and PrPres types in the brain. In all cases with frozen retinal tissue available (n = 18), the immunoblot was positive for PrPres . Two out of the 51 sCJD showed the deposition of PrPres also in the optic nerve, corresponding to an immunostaining delineating stellate cells and associated with the presence of numerous CD68- and CD45-positive cells. Our results demonstrate the presence of the pathological form of prion protein not only in the retina of all sCJD cases analysed, but also in optic nerve in a small subset of sCJD patients, a finding previously described only in variant CJD and in experimental animal models. Moreover, our data suggest a correlation between the deposition of PrPres and inflammatory changes in the optic nerve in sCJD.

143

http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf



----- Original Message ----- From: "Terry S. Singeltary Sr." <[log in to unmask]> To: <[log in to unmask]> Sent: Thursday, December 28, 2006 10:23 AM Subject: Ophthalmic Surgery in Prion Diseases

Volume 13, Number 1–January 2007 Dispatch Ophthalmic Surgery in Prion Diseases Tsuyoshi Hamaguchi,*1 Moeko Noguchi-Shinohara,* Yosikazu Nakamura,†2 Takeshi Sato,‡2 Tetsuyuki Kitamoto,§2 Hidehiro Mizusawa,¶2 and Masahito Yamada*2 *Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; †Jichi Medical University, Shimotsuke, Japan ‡National Center for Neurology and Psychiatry, Ichikawa, Japan; §Tohoku University Graduate School of Medicine, Sendai, Japan; and ¶Tokyo Medical and Dental University, Tokyo, Japan

Suggested citation for this article

Abstract Eleven (1.8%) of 597 patients underwent ophthalmic surgery within 1 month before the onset of prion disease or after the onset. All ophthalmologists reused surgical instruments that had been incompletely sterilized to eliminate infectious prion protein. Ophthalmologists should be aware of prion diseases as a possible cause of visual symptoms and use disposable instruments whenever possible.

Visual impairment occurs in 10% to 20% of patients with sporadic Creutzfeldt-Jakob disease (sCJD) during an early stage of the disease (Heidenhain variant) (1,2). Some patients with prion diseases may visit ophthalmologists with visual impairment due to prion diseases or with coexisting age-related eye diseases (3,4).

Infectious prion protein (PrPSc) was identified in the retina and optic nerve in patients with variant CJD (vCJD) and sCJD (5,6), and CJD has been transmitted by corneal transplantation (7,8). In the World Health Organization (WHO) guidelines, eyes were classified as highly infectious tissues (9).

Secondary transmission of PrPSc through ophthalmic surgery could possibly be prevented around the onset of prion diseases, although surgery that is performed long before the onset of prion diseases would not have that potential. It is important to understand the current status of ophthalmic surgery for patients with prion diseases and to clarify the clinical features of the patients with prion diseases who undergo ophthalmic surgery. Here, we describe the relevant data from CJD surveillance in Japan.

The Study.....snip full text ;

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0612&L=sanet-mg&P=24255


----- Original Message ----- From: "Terry S. Singeltary Sr." <[log in to unmask]> To: <[log in to unmask]> Sent: Wednesday, December 27, 2006 12:21 PM Subject: ABNORMAL PRION ACCUMULATION ASSOCIATED WITH RETINAL PATHOLOGY IN EXPERIMENTALLY INOCULATED SCRAPIE-AFFECTED SHEEP

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0612&L=sanet-mg&P=24048


Eye procedure raises CJD concerns

November 19, 2004 United Press International by STEVE MITCHELL

A New York man who died from a rare brain disorder similar to mad cow disease in May underwent an eye procedure prior to his death that raises concerns about the possibility of transmitting the fatal disease to others, United Press International has learned. The development comes on the heels of the announcement Thursday by U.S. Department of Agriculture officials of a possible second case of mad cow disease in U.S. herds.

Richard Da Silva, 58, of Orange County, N.Y., died from Creutzfeldt Jakob disease, an incurable brain-wasting illness that strikes about one person per million.

Richard's wife Ann Marie Da Silva told UPI he underwent a check for the eye disease glaucoma in 2003, approximately a year before his death. The procedure involves the use of a tonometer, which contacts the cornea -- an eye tissue that can contain prions, the infectious agent thought to cause CJD.

Ann Marie's concern is that others who had the tonometer used on them could have gotten infected.

A 2003 study by British researchers suggests her concerns may be justified. A team led by J.W. Ironside from the National Creutzfeldt-Jakob Disease Surveillance Unit at the University of Edinburgh examined tonometer heads and found they can retain cornea tissue that could infect other people -- even after cleaning and decontaminating the instrument.

"Retained corneal epithelial cells, following the standard decontamination routine of tonometer prisms, may represent potential prion infectivity," the researchers wrote in the British Journal of Ophthalmology last year. "Once the infectious agent is on the cornea, it could theoretically infect the brain."

Prions, misfolded proteins thought to be the cause of mad cow, CJD and similar diseases, are notoriously difficult to destroy and are capable of withstanding most sterilization procedures.

Laura Manuelidis, an expert on these diseases and section chief of surgery in the neuropathology department at Yale University, agreed with the British researchers that tonometers represent a potential risk of passing CJD to other people.

Manuelidis told UPI she has been voicing her concern about the risks of corneas since 1977 when her own study, published in the New England Journal of Medicine, showed the eye tissue, if infected, could transmit CJD.

At the time the procedure was done on Richard Da Silva, about a year before he died, she said it was "absolutely" possible he was infectious.

The CJD Incidents Panel, a body of experts set up by the U.K. Department of Health, noted in a 2001 report that procedures involving the cornea are considered medium risk for transmitting CJD. The first two patients who have a contaminated eye instrument used on them have the highest risk of contracting the disease, the panel said.

In 1999, the U.K. Department of Health banned opticians from reusing equipment that came in contact with patients' eyes out of concern it could result in the transmission of variant CJD, the form of the disease humans can contract from consuming infected beef products.

Richard Da Silva was associated with a cluster of five other cases of CJD in southern New York that raised concerns about vCJD.

None of the cases have been determined to stem from mad cow disease, but concerns about the cattle illness in the United States could increase in light of the USDA announcement Thursday that a cow tested positive on initial tests for the disease. If confirmed, this would be the second U.S. case of the illness; the first was detected in a Washington cow last December. The USDA said the suspect animal disclosed Thursday did not enter the food chain. The USDA did not release further details about the cow, but said results from further lab tests to confirm the initial tests were expected within seven days.

Ann Marie Da Silva said she informed the New York Health Department and later the eye doctor who performed the procedure about her husband's illness and her concerns about the risk of transmitting CJD via the tonometer.

The optometrist -- whom she declined to name because she did not want to jeopardize his career -- "didn't even know what this disease was," she said.

"He said the health department never called him and I called them (the health department) back and they didn't seem concerned about it," she added. "I just kept getting angrier and angrier when I felt I was being dismissed."

She said the state health department "seems to have an attitude of don't ask, don't tell" about CJD.

"There's a stigma attached to it," she said. "Is it because they're so afraid the public will panic? I don't know, but I don't think that the answer is to push things under the rug."

New York State Department of Health spokeswoman Claire Pospisil told UPI she would look into whether the agency was concerned about the possibility of transmitting CJD via tonometers, but she had not called back prior to story publication.

Disposable tonometers are readily available and could avoid the risk of transmitting the disease, Ironside and colleagues noted in their study. Ann Marie Da Silva said she asked the optometrist whether he used disposable tonometers and "he said 'No, it's a reusable one.'"

Ironside's team also noted other ophthalmic instruments come into contact with the cornea and could represent a source of infection as they are either difficult to decontaminate or cannot withstand the harsh procedures necessary to inactivate prions. These include corneal burrs, diagnostic and therapeutic contact lenses and other coated lenses.

Terry Singletary, whose mother died from a type of CJD called Heidenhain Variant, told UPI health officials were not doing enough to prevent people from being infected by contaminated medical equipment.

"They've got to start taking this disease seriously and they simply aren't doing it," said Singletary, who is a member of CJD Watch and CJD Voice -- advocacy groups for CJD patients and their families.

U.S. Centers for Disease Control and Prevention spokeswoman Christine Pearson did not return a phone call from UPI seeking comment. The agency's Web site states the eye is one of three tissues, along with the brain and spinal cord, that are considered to have "high infectivity."

The Web site said more than 250 people worldwide have contracted CJD through contaminated surgical instruments and tissue transplants. This includes as many as four who were infected by corneal grafts. The agency noted no such cases have been reported since 1976, when sterilization procedures were instituted in healthcare facilities.

Ironside and colleagues noted in their study, however, many disinfection procedures used on optical instruments, such as tonometers, fail. They wrote their finding of cornea tissue on tonometers indicates that "no current cleaning and disinfection strategy is fully effective."

Singletary said CDC's assertion that no CJD cases from infected equipment or tissues have been detected since 1976 is misleading.

"They have absolutely no idea" whether any cases have occurred in this manner, he said, because CJD cases often aren't investigated and the agency has not required physicians nationwide report all casesof CJD.

"There's no national surveillance unit for CJD in the United States; people are dying who aren't autopsied, the CDC has no way of knowing" whether people have been infected via infected equipment or tissues, he said.

Ann Marie Da Silva said she has contacted several members of her state's congressional delegation about her concerns, including Rep. Sue Kelly, R-N.Y., and Sen. Charles Schumer, D-N.Y.

"Basically, what I want is to be a positive force in this, but I also want more of a dialogue going on with the public and the health department," she said.

http://www.upi.com/NewsTrack/Science/2004/11/18/eye_procedure_raises_cjd_concerns/2974/

http://www.organicconsumers.org/madcow/CJD111904.cfm


Cadaver corneal transplants -- without family permission Houston, Texas channel 11 news 28 Nov 99 Reported by Terry S. Singeltary Sr.son of CJD victim

http://www.mad-cow.org/dec99_news.html#bbb




Subject: RE-The Eyes Have It (cjd) and they could be stealing them from your loved one... "pay back time" Date: Sat, 16 Sep 2000 10:04:26 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de

######### Bovine Spongiform Encephalopathy #########

Greetings List Members,

I hate to keep kicking a madcow, but this still is very disturbing to me. Not only for the recipient of the cornea's, but as well, for the people whom would be operated on, using the same tools that were used to put those stolen cornea's in the recipient with. No history of this donor or his family (re-ffi), or anything would be known, using stolen organs and or tissue's. I just think this is not only wrong, but very dangerous to a great many other people, as this is one of the most infectious tissues of TSE's. It seems that this practice of stealing organ/tissue happens more than we think. Anyway, the family of the victim which had their cornea's stolen, are now suing. In the example I used with my Mother, if 3 months before, she would have been in a catastrophic accident (car wreck, whatever), no autopsy (for whatever reason), no family (for whatever reason), she lay in the morgue, and after 4 hours, they come steal the cornea's, lot of people could have been infected, just because of lack of medical history of donor/family. It may be hypothetical, but very real. We need to stop the spread of this disease.

kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA ===========================================

Previous story--

Cadaver corneal transplants -- without family permission...



http://www.mad-cow.org/~tom/dec99_news.html#bbb



===============================================



Sept. 15, 2000, 11:39PM

Slain woman's family sues over missing eyes

By BILL MURPHY Copyright 2000 Houston Chronicle

The family of a woman who was stabbed to death last year has filed a lawsuit accusing the Lions Eye Bank of Houston of removing the woman's eyes without permission and inserting plastic discs in their place.

Daisy Diaz's relatives were horrified when they saw her body and noticed her eyes were missing, said their lawyer, Duncan Neblett III.

"They're a Catholic family," Neblett said. "They have strong beliefs about the body and burial. They were really upset by this."

Dorey Zidrow, the eye bank's spokeswoman, said she could not specifically discuss the Diaz case because it was in litigation. But Zidrow said a state law allows doctors to remove corneas -- the dime-sized lens near the eye's surface -- from a corpse without the family's permission.

The eye bank's usual procedure calls for removing the corneas, Zidrow said, but not the entire eyes.

"There are an awful lot of people who benefit from this program in the state of Texas," she said.

Diaz, 25, was stabbed to death in her apartment in the 400 block of Thornton in October. Her brother-in-law, 30-year-old Raudel Quiroz, is charged in the killing but has not been caught.

Neblett said authorities have told him Quiroz may have returned to his native Guatemala.

Neither Diaz nor her family had given permission to donate any of her organs, Neblett said.

Although state law allows corneas to be removed from corpses without first gaining the family's permission, they cannot be removed over the family's stated objection.

The eye bank is located at, and staffed by, the Baylor College of Medicine, and receives part of its funding from the Lions Club.

The Diaz lawsuit is the second such suit to be filed against the eye bank in recent years.

The family of Levi Perry Jr., a Houston teacher shot to death in MacGregor Park in 1994, also alleged in their suit that Perry's eyes were removed. The family was awarded $345,000 from the eye bank in April 1999.

http://www.chron.com/cs/CDA/story.hts/metropolitan/669555



==========================================================



THE LEGALITY OF STEALING ORGAN/TISSUE...

TEXAS STATUTES

Sec. 693.012. Removal of Corneal Tissue Permitted Under Certain Circumstances.

On a request from an authorized official of an eye bank for corneal tissue, a justice of the peace or medical examiner may permit the removal of corneal tissue if:

(1) the decedent from whom the tissue is to be removed died under circumstances requiring an inquest by the justice of the peace or medical examiner;

(2) no objection by a person listed in Section 693.013 is known by the justice of the peace or medical examiner; and

(3) the removal of the corneal tissue will not interfere with the subsequent course of an investigation or autopsy or alter the decedent's postmortem facial appearance.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.012 -------------------------------------------------------- TEXAS STATUTES Sec. 693.003. Consent Required in Certain Circumstances.

(a) A medical examiner or a person acting on the authority of a medical examiner may not remove a visceral organ unless the medical examiner or person obtains the consent of a person listed in Section 693.004.

(b) If a person listed in Section 693.004 is known and available within four hours after death is pronounced, a medical examiner or a person acting on the authority of a medical examiner may not remove a nonvisceral organ or tissue unless the medical examiner or person obtains that person's consent.

(c) If a person listed in Section 693.004 cannot be identified and contacted within four hours after death is pronounced and the medical examiner determines that no reasonable likelihood exists that a person can be identified and contacted during the four-hour period, the medical examiner may permit the removal of a nonvisceral organ or tissue.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.003 -------------------------------------------------------- PLEASE NOTE; the bottom would only pertain to those who know of the law. if you don't know about it, you cannot dispute, so in four hours, they can legally remove body organs, as long as they don't disfigure. and who is to know the difference? makes me wonder of some of my dead relatives, and if they were burried with their eye's and or any of their organs. This is very disturbing, if not for moral reasons, but for the risk of dangerous pathogens (human TSE's, etc.) to be transmitted. only time will tell, but i am very disturbed. these laws are not morally correct. They should be re-written as to they cannot so easily take your organs, with no one knowing. The Family or Victim, must consent. There should be some kind of research on donor/family medical history...TSS --------------------------------------------------------

Sec. 693.013. Persons Who May Object to Removal.

The following persons may object to the removal of corneal tissue:

(1) the decedent's spouse;

(2) the decedent's adult children, if there is no spouse;

(3) the decedent's parents, if there is no spouse or adult child; or

(4) the decedent's brothers or sisters, if there is no spouse, adult child, or parent.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.013 ------------------------------------------------------- to cover one's butt....

Sec. 693.014. Immunity From Damages in Civil Action.

(a) In a civil action brought by a person listed in Section 693.013 who did not object before the removal of corneal tissue, a medical examiner, justice of the peace, or eye bank official is not liable for damages on a theory of civil recovery based on a contention that the person's consent was required before the corneal tissue could be removed.

(b) Chapter 104, Civil Practice and Remedies Code, applies to a justice of the peace, medical examiner, and their personnel who remove, permit removal, or deny removal of corneal tissue under this subchapter as if the justice of the peace, medical examiner, and their personnel were state officers or employees.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th Congress. The 76th session of the Texas Legislature has concluded. The State of Texas has not yet made the new codes available to the public. Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.014

[[[as you can see, they knew it was wrong when they wrote the laws. or they would not have covered the rear-ends so well...TSS]]] --------------------------------------------------------- thanks again, kind regards, Terry S. Singeltary Sr.

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############



CJD, they eye's have it and they could be stealing them from your loved one

http://www.mad-cow.org/dec99_news.html#bbb



Subject: RE-The Eyes Have It (cjd) and they could be stealing them from your loved one... "pay back time" Date: Sat, 16 Sep 2000 10:04:26 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de

######### Bovine Spongiform Encephalopathy #########

Greetings List Members,

I hate to keep kicking a madcow, but



http://creutzfeldt-jakob-disease.blogspot.com/2008/01/cjd-hgh-body-snatchers.html


http://creutzfeldt-jakob-disease.blogspot.com/2008_01_01_archive.html




CJD and Ophthalmology* May 4, 2004

http://www.rcophth.ac.uk/docs/publications/CollegeCJDNov2003.pdf




Subject: RE--[Docket No. 03D-0118] Guidance for FDA Staff on Sampling or Detention Without Physical Examination of Decorative Contact Lenses (Import Alert 86-10)

Date: Mon, 07 Apr 2003 15:18:04 -0500

From: "Terry S. Singeltary Sr." To: fdadockets@oc.fda.gov



TSS SUBMISSION TO [Docket No. 03D-0118]



I would kindly like to submit to [Docket No. 03D-0118]

Guidance for FDA Staff on Sampling or Detention Without Physical Examination of Decorative Contact Lenses (Import Alert 86-10); Availability.

My concerns relate to human/animal TSEs Transmissible Spongiform Encephalopathies and all variants and the potential risks from the cosmetic RE-USE of these products IF re-use takes place in the USA. i am aware of such practices in the UK and recently ask where i received my new glasses if this practice of re-use of _trial_ contact lenses takes place. he was aware of only one type lens that this practice takes place with. i kindly informed him that this practice could potentially spread this agent and hoped he would look into it. other concerns of mine are with children and the _sharing_ of such contact lenses. if regulation are lax to the point of say (nutritional supplements), where there really are no regulations, the potential for many pathogens via the eye's are a very real threat, especially since the titre of infectivity for TSEs has recently been lowered to .1 gram for being LETHAL. i hope that the data below will provide enough information for further investigations into my concerns of RE-USE OF Contact lenses and potential exposure to human TSEs;

(Investigative Ophthalmology and Visual Science. 2003;44:342-346.) © 2003 by The Association for Research in Vision and Ophthalmology, Inc.

Prion Protein Accumulation in Eyes of Patients with Sporadic and Variant Creutzfeldt-Jakob Disease

Mark W. Head1, Victoria Northcott1, Kathleen Rennison1, Diane Ritchie1, Linda McCardle1, Tristan J. R. Bunn1, Neil F. McLennan1, James W. Ironside1, Andrew B. Tullo2 and Richard E. Bonshek2

1 From the National Creutzfeldt-Jakob Disease Surveillance Unit and Department of Pathology of the University of Edinburgh, Scotland, United Kingdom; and the 2 Academic Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, United Kingdom.

PURPOSE. Creutzfeldt-Jakob disease (CJD) primarily affects the brain. This study was conducted to assess the possible involvement of the eye in sporadic and variant CJD by testing for the presence of the disease-associated, protease-resistant isoform of the prion protein (PrPSc) in ocular tissue.

METHODS. Human eyes from donors with CJD and non-prion neurodegenerative disease control eyes were studied. In situ hybridization and Western blot analysis were used to determine the normal pattern of cellular prion protein (PrPC) expression. Western blot analysis and immunohistochemistry were then used to determine the localization, abundance, and isotype of PrPSc in eyes in CJD.

RESULTS. PrPC was expressed in the nuclear layers of the retina. In both the sporadic and variant forms of CJD, PrPSc accumulated throughout the synaptic layers of the retina. The levels of PrPSc found in the retina were comparable with those found in the brain. Lower levels of PrPSc could be found in the optic nerve, but no PrPSc was detectable in other ocular tissues. The glycoform ratio of PrPSc in the retina did not correspond to that found in the brain.

CONCLUSIONS. Presumptive centrifugal spread of PrPSc from the brain through the optic nerve occurs in two major types of CJD. PrPSc is a marker of CJD infectivity. Given that routine decontamination may not remove PrPSc from surgical instruments, a careful risk assessment should be made of possible iatrogenic spread of sporadic and variant CJD after surgery to the retina or optic nerve.

http://www.iovs.org/cgi/content/abstract/44/1/342


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12506094&dopt=Abstract


Organ distribution of prion proteins in variant Creutzfeldt-Jakob disease

Summary

In this article we give an overview of the transmissible spongiform encephalopathies, with emphasis on the evidence for the distribution of abnormal prions in tissues. The normal prion protein is distributed ubiquitously throughout human body tissues. Endogenous expression of the normal prion protein, as well as auxiliary proteins, plays a part in accumulation of the abnormal prion protein. As exemplified by variant Creutzfeldt-Jakob disease (vCJD) the abnormal prion protein can accumulate in the host lymphoid system, in particular the follicular dendritic cells. The route for the disease-related prion neuroinvasion is likely to involve the peripheral nervous system. An alternative route may involve blood constituents. Both animal studies and studies on vCJD patients suggest a potential for abnormal prion distribution in several peripheral tissues other than the lymphoreticular system. In human beings the abnormal prion has been reported in the brain, tonsils, spleen, lymph node, retina, and proximal optic nerve. Infectivity, although present in peripheral tissues, is at lower levels than in the central nervous system (CNS). Animal models suggest that the growth of infectivity in the CNS is likely to be gradual with maximum values during the clinical phase of disease. That tissues may harbour the abnormal prion, at different levels of infectivity, during the incubation period of the disease raises concerns of iatrogenic transmission of the disease either after surgery, blood transfusion, or accidental organ transplantation from donors in the preclinical phase of the disease.

Affiliations: a IR and FB are at the Communicable Diseases and Environmental Health Branch, Department of Health, Canberra, Australia. b ML is at the National Centre for HIV Epidemiology and Clinical Research, Darlinghurst, Australia. c SC is at the Department of Pathology, University of Melbourne, Victoria, Australia.

http://infection.thelancet.com/journal/vol3/iss4/abs/laid.3.4.review_and_opinion.25026.1


Royal College of Ophthalmologists Guidelines Creutzfeldt-Jakob Disease (CJD) and Ophthalmology

Background In the Clinic In the Operating Theatre Surgical Procedures on the Posterior Eye Ocular Tissue Transplantation Action if exposure to contamination takes place Patient Risk Groups

1. Background

Patients with classical (sporadic) CJD are predominantly in their 60s and as such may come into contact with ophthalmologists because of cataract, glaucoma and macular degeneration, or because of visual symptoms caused by their condition1. Although there is no clear evidence of the transmission of spongiform encephalopathy from one patient to another by ophthalmic surgery other than through corneal transplantation2, it has been accepted for many years that instruments used on patients with known or suspected CJD undergoing any surgical procedure, should be destroyed3.

The number of individuals in the UK who may develop variant CJD (vCJD), believed to be the human form of BSE, is unknown but may yet number tens of thousands who may be infectious before their symptoms develop. The Department of Health (DH) has identified ophthalmology as an area of risk second only to neurosurgery, though other forms of surgery, e.g. on the gut and tonsils, could also lead to contamination of instruments by prions which routine decontamination does not eradicate. Research is in progress to establish the efficacy of current and improved methods of decontamination in removing prion protein.

The only certain way to avoid the as yet unquantifiable risks of ophthalmic devices and instruments being vectors of transmissible prions would be for them all to be disposable, though this is currently impossible without severely compromising patient care. In 1999, the Medical Devices Agency issued Advice Notes on contact lenses4 and on devices5 that touch the eye, though their full implementation at that time was not feasible. The College of Optometrists and the Association of British Dispensing Opticians have since agreed the case with the DH for a more pragmatic approach and have published practical guidance6 which was circulated to their members in October 2001.

There are, however, situations where improved awareness and changes in clinical practice can be implemented without compromising other standards or necessarily increasing costs, in order to minimise the risk of transmission of prion protein.

2. In the Clinic Back to top

2.1 A significant proportion of patients with classical CJD present with visual disturbance. Key features3 which should raise suspicion are:

2.1.1 Unexplained visual loss in the middle-aged and elderly.

2.1.2 Homonymous hemianopia in the absence of evidence of space-occupying lesion or CVA on MRI scan.

2.2 For any patient, including those being pre-operatively assessed for surgery, the possible onset of either form of CJD should be considered. The features of vCJD to date have not included visual symptoms until the late stages, though it should be noted that this form of disease occurs in much younger people (median age 29)7. Suspicion should be raised in any patient under the age of 50 years who, in the preceding year, has experienced new psychiatric or neurological symptoms sufficient to warrant referral to a psychiatrist or neurologist8.

2.3 Tonometry: disposable tonometer heads9, tonometer shields10 or Tonopens are essential for the patient who is known to have or is under suspicion of having CJD (see Table 1). One or more of these devices should be available in all departments11.

2.4 Re-usable tonometer heads: tonometer prisms should not be moved between clinical workstations, clinics and departments, to facilitate tracing and so that their life may be more readily determined for the purpose of regular replacement. Current methods of hygiene are acceptable, but it should be noted that the manufacturer Haag-Streit AG has determined12 that Goldmann tonometer prisms may be re-used 100 times following immediate cleaning and subsequent disinfection in sodium hypochlorite solution of (in Haag-Streit's own example, greater than) 2% for one hour at room temperature. If this method is used, tonometer heads should then be rinsed thoroughly in sterile saline or boiled water and wiped dry.

2.5 Soft and rigid contact lenses: ideally all contact lenses should be for the use of one individual only. Nowadays most contact lens wearers use disposable soft lenses. These, and some other soft and rigid lenses, can be fitted empirically and will never need to be re-used on other wearers. Exceptions have to be made for 'special complex diagnostic contact lenses6' in fitting sets and it has been established that these lenses (both corneal and scleral) may be decontaminated without damage using 20,000 ppm available chlorine from sodium hypochlorite solution (e.g. 2% Milton Sterilising Fluid) for 1 hour6 after which they must be thoroughly rinsed in sterile saline (e.g. 3 full rinses in a 10ml contact lens case is adequate to dilute residual chlorine to a safe level of 1 ppm) and then disinfected in the normal way, e.g. dry storage or disinfectant solution storage.

2.6 It is recommended that between patients examination (diagnostic) contact lenses (e.g. gonio, 3-mirror and fundus lenses) are wiped clean whilst moist before the face of the lens is immersed in the disinfection fluid normally used. At the end of each session they should be cleaned with detergent, rinsed thoroughly in sterile saline and then wiped dry. Work on the compatibility of such devices with sodium hypochlorite 2% solution is not yet complete. Diagnostic contact lenses should not be moved between clinics and departments.

3. In the Operating Theatre Back to top

3.1 All instruments and devices marketed as being disposable must be disposed of after single use13.

3.2 By March 2002, all personnel involved with any operation in any surgical discipline, including Ophthalmology, and the instrument trays, must be identifiable and traceable13.

3.3 The cleaning of surgical instruments is now recognised to be even more important than autoclaving in removing prion protein. Instruments should be cleaned in washer disinfectors of a modern and high standard14.

3.4 If a patient is known to be suffering from, or is at risk of either form of CJD (see Table 1), all instruments and devices must be segregated and destroyed by incineration after use3.

3.5 If a patient is suspected to be suffering from any form of CJD, consideration may be given to deferring surgery in order to allow clinical signs to be observed or for a further opinion to be sought. If surgery is deemed urgent, then consideration should be given to the operation, if possible, being carried out entirely with single-use instruments. If this is not possible, at the end of the procedure:

3.5.1 Re-usable instruments should be placed in an impervious plastic container with a close-fitting lid and sealed with heavy-duty tape. The box must be labelled with the patient's identification details, the surgical procedure for which the instruments were used and the name of the responsible person (theatre manager).

3.5.2 The box must be stored indefinitely in a designated place until the results of further investigations are known.

3.5.3 If the patient is confirmed as suffering from any form of CJD, the sealed box and its contents must remain undisturbed and be incinerated.

3.5.4 If an alternative and confirmed diagnosis is established, the instruments may be removed from the box by the responsible person and be sent to CSSD for processing in the normal way. The CSSD must be informed of this decision before the instruments are transported.

3.6 Surgical Procedures on the posterior eye Back to top

3.6.1 Recent evidence from studies on the eyes of patients who have died from classical or vCJD show that prion protein is present in the retina and optic nerve, but not elsewhere in the eye, using the methods of Western blotting and peroxidase staining15.

3.6.2 All instruments that penetrate the optic nerve sheath, e.g. enucleation snares or scissors, and evisceration spoons, should be traceable to individual patients, or preferably disposed of after single use.

3.6.3 Some instruments used in vitreoretinal surgery are already for single use, and efforts are continuing to develop alternatives to those that are not currently disposable.

3.6.4 For each essential non-disposable instrument that enters the vitreous cavity or comes close to or touches the retina, e.g. membrane scissors, the patient on whom they are used should be identifiable.

4. Ocular Tissue Transplantation Back to top

4.1 Guidelines on donor exclusion criteria and the retrieval of human ocular tissue for transplantation and research are already available16 are regularly revised and are carefully utilised by eye banks. Currently the only way to exclude donors known or suspected to have CJD is through the medical and behavioural history.

4.2 Suggested information for transplant recipients that specifically mentions remote risk of disease transmission is also available16.

4.3 Eye retrieval is now possible and recommended using disposable instruments17.

4.4 Eye Banks are advised that disposable instruments are now also available for all stages of processing17.

4.5 During corneal transplantation, all trephines and trephine blocks should be disposed of after single use.

4.6 Eye banks in the UK will continue to provide sclera on request, though the proximity of the sclera to the retina and optic nerve, where prion proteins may be present15, suggests that if alternative methods and materials are available, and that these should be given due consideration by surgeons.

4.7 It is essential that records of all ocular donor tissue are kept by eye banks; details of surgery should be recorded on the Royal College/UKT Transplant Record Form (or similar), and returned to the UK Transplant Information Executive.

4.8 The ability to trace all recipients of ocular tissue transplants and to monitor outcome are key components of a surgeon's responsibility. Completion of the Royal College/UKT Follow-up Forms is strongly encouraged for at least 5 years following corneal transplantation for penetrating and lamellar keratoplasty.

4.9 Surgeons should, through their Hospital Manager, ensure that hospital records of transplant recipients should be kept for at least 8 years after the patient has died or been lost to follow-up.

NB: Ocular tissue transplant recipients are currently not accepted as blood donors.

5. Action if exposure to contamination takes place Back to top

The CJD Incidents Panel (established November 2000) has already received several reports of ophthalmic incidents since September 1999, concerning known or suspected sporadic CJD, mostly involving cataract surgery. If a patient undergoing ophthalmic surgery subsequently develops any form of CJD, it is desirable that all instruments and devices involved should be traceable and taken out of circulation, and that subsequent patients who may have inadvertently been put at risk can be identified. For further advice in such an event contact Dr Philippa Edwards, Department of Health, Skipton House, 80 House Road, London, SE1 6LH, tel: 0207 - 972 5324, e-mail: claire.mills@doh.gsi

NB: A consultation document from the CJD Panel is accessible on www.doh.gov.uk/cjd/consultation

References: Back to top

1 Lueck CJ, McIlwaine GC, Zeidler M. CJD and the Eye. II. Ophthalmic and Non-Ophthalmic Features, Eye 2000; 14: 291-301

2 Hogan RN, Brown P, Heck E, Cavanagh HD. Risk of Prion Disease Transmission from Ocular Donor Tissue Transplantation, Cornea 1999; 18: 2-11

3 HSC 1988 1 (Annex 1)

4 MDA AN1999 (03): Single patient use of contact lenses: implications for clinical practice. Medical Devices Agency, October 1999

5 MDA AN 1999 (04): Single patient use of ophthalmic medical devices: implications for clinical practice. Medical Devices Agency, October 1999

6 College of Optometrists and Association of British Dispensing Opticians, September 2001: Guidance on the Re-Use of Contact Lenses and Ophthalmic Devices

7 Will RG, Ironside JW, Zeidler M et al. A New Variant of Creutzfeldt-Jakob Disease in the UK, Lancet 1996; 347: 921-5

8 Will RG et al: Psychiatric features of new variant Creutzfeldt-Jakob Disease, Psychiatric Bulletin 1999: 23; 264-7

9 Clement Clarke International Limited, Edinburgh Way, Harlow, Essex, CM20 2TT (Fax. 01279-635232)

10. Kestrel Healthcare Ltd, Network House, Basing View, Basingstoke, Hampshire, RG21 4HG (Tel. 01256-307580, Fax. 01256-307590)

11. Desai SP, Sivakumar S, Fryers PT. Evaluation of a disposable prism for tonometry, Eye 2001; 15: 279-282

12. Haag-Streit Dok. Nr. 9202 9200066 01010, 1998: Desinfektion der Haag-Streit Kontacktgläser und Tonometermesskörper

13. MDA DB 2000(04): Single-use Medical Devices: Implications and consequences of reuse

14. HSC 2000/032 Decontamination of Medical Devices

15. Wadsworth JDF, Joiner S, Hill AF, et al. Tissue distribution of protease-resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay, Lancet 2001: 358; 171-80

16. www.rcophth.ac.uk

17. AMG Medical Products, 48 Church Street, Shipston on Stour, Warwickshire, CV36 4AS (Tel: 01608 662029; Fax 01608 663222).

Further Reading: Back to top

HSC 1999/178: Variant Creutzfeldt-Jakob disease (vCJD): Minimising the risk of transmission, NHS Executive, August 1999

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection, Advisory Committee on Dangerous Pathogens, 1998

Tullo AB, Buckley RJ, Painter M. CJD and the Eye, Eye 2000; 14: 259-260

Anderson S, Kaye SB, Tullo AB, Hart CA. CJD and Optometry: What are the risks? Optometry Today 2001

Table 1 Patient Risk Groups Back to top Known or at-risk patients Suspected patients

Patients diagnosed as having CJD or a related disorder*

Asymptomatic patients who are potentially at risk of developing CJD or a related disorder, i.e. - recipients of hormone derived from human pituitary glands, e.g. growth hormone, gonadotrophin - recipients of human dura mater grafts; - people with a family history of an inherited form of CJD or related disorder, i.e. close blood line relatives (parents, brothers, sisters, children, grandparents and grandchildren); sometimes patients may be uncertain of the type of CJD of which their relative(s) dies; in such circumstances, if two or more family members have been diagnosed as CJD patients, this is a good indication that it is the inherited form of the disease. Patients suspected of having CJD or a related disorder* i.e. whose clinical symptoms are suggestive of CJD but where the diagnosis has not yet been confirmed. * i.e. classical sporadic CJD, vCJD, Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia and kuru

January, 2002

http://www.site4sight.org.uk/Quality/RGov/Guidelines/CJD2.htm


Optometric practice does not expose patients to potentially infective procedures except via mucus membrane contact or contact with the cornea. This would include the use of contact lens fitting sets and tonometer heads. It is as yet unknown how reliable a route of transmission this is likely to be. The Spongiform Encephalopathy Advisory Committee (SEAC) advised in June 1999 that optometrists should not reuse trial contact lenses. Used trial lenses should be safely disposed of after use71. However, the recent publication of a study shows that although the prion responsible for vCJD is present in significant quantities in the optic nerve and retina, it could not be detected in the anterior segment of the eye of a vCJD victim. This has led to new recommendations by SEAC published in July 2001. These have been adopted by the College of Optometrists that has issued guidelines for the reuse of contact lenses and ophthalmic devices73.

In essence, these suggest that wherever practicable contact lenses or devices that come into contact with the eye should be disposed of after use. If the practitioner judges that only a reusable item is suitable, for example where a special complex diagnostic contact lens is needed the patient should be advised of the risks and benefits of the use of this item. After use it should be soaked in 2% sodium hypochlorite for one hour in addition to the normal cleaning procedure. The device should then be thoroughly rinsed. The practitioner concerned should keep a full record of the use of each contact lens. If the patient is in a high-risk category for the development of CJD even reusable item should always be disposed of immediately after use. The full guidelines are available from the College of Optometrists.

Diagnostic and treatment contact lenses such as goniscopy and fundus view contact lenses are not available in a disposable form. Volk advises us that any contact with sodium hypochlorite or heat sterilisation will have detrimental effects on the lenses. They suggest either ethylene oxide or the STERIS process, neither of which has been shown to be effective in the destruction of prions. Haag-Streit has published that tonometer heads may safely be disinfected in 2% sodium hypochlorite up to 100 times. This would make it marginally cheaper to use the disposable type of tonometer (Tonosafe™) (Figure 1) if the practitioner did this procedure frequently as well as complying with the above guidelines. Unpublished data mentioned in the College of Optometrists’ guidelines suggests that a one-hour soak in 2% sodium hypochlorite at room temperature did not effect the physical characteristics of rigid contact lenses. While sporadic CJD is a very rare disease, the full scale of the variant CJD epidemic is still unknown. It seems extremely unlikely that either of these diseases would be passed on by routine optometric practice. Given, however, that the risk is unknown and many patients (especially those being fitted for contact lenses) are young and healthy, it is appropriate that guidelines are now available to further minimise any risks.

AGENTS FOUND TO BE INEFFECTIVE AGAINST CJD • Alcohol67 • Hydrogen peroxide67. • Sodium dichloroiocyanurate (e.g. Presept)68 • Moist heat at 121°C for 15 minutes67 • Formalin (actually increased resistance to disinfection with heat)60 AGENTS FOUND TO BE EFFECTIVE AGAINST CJD • 8,259ppm available chlorine/sodium hypochlorite for 1/2 hour68 • 2M sodium hydroxide for 1 hour (not fully effective)68 • Porous load steamer 134-137°C for 18 minutes (not fully effective)68 • Phenol60 • Guanidine thiocyanate60

Further reading • Lueck C, Ocular features of CJD. Optician2000; 220: 23-27 • Lueck C J, McIlwaine G G, Zeidler M. Creuzfeld-Jacob disease and the eye. 1. Background and patient management. Eye 2000; 14:263-290 • Lueck C J, McIlwaine, Zeidler M, Creutzfeldt-Jacob disease and the eye. II. Ophthalmic and neuro-ophthalmic features. Eye 2000; 14:291-301 • The College of Optometrists, The Association of British Dispending Opticians. Guidance on the re-use of contact lenses and ophthalmic devices October 2001. About the authors Sarah Anderson is a Specialist Registrar in Ophthalmology at the Royal Liverpool University Hospital. Stephen Kaye is a Consultant Ophthalmologist at the Royal Liverpool University Hospital. Andrew Tullo is a Consultant Ophthalmologist at Manchester Royal Infirmary. Charles Hart is a Professor of Medical Microbiology at the Royal Liverpool University Hospital. References For a list of references please fax 01252-816176 or e-mail: robina@optometry.co.uk 26 ot October 19, 2001 OT www.optometry.co.uk

FULL TEXT;

http://www.optometry.co.uk/articles/20011019/anderson20011019.pdf

Subject: Trial Contact Lenses and RE-USE in the U.S. & CJD, no threat says FDA??? Date: Sat, 7 Oct 2000 10:27:03 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de

######### Bovine Spongiform Encephalopathy #########

Greetings List Members,

It just never ceases to amaze me, that the FDA and the rest of the different political governmental bodies that are suppose to protect us, but instead, choose to protect their best interest$ the corporate industries that donate all the cash$ there has been plenty of warning and tests to prove of some sort of infectivity in the eyes. the fda speaks of no test for the tears, well hell, there is no test that will detect it period, but yet you still die from it. does not mean it is not there. when will they wake up? sporadic CJD is coming from somewhere and they had better start looking as to where it is coming from. this is just more typical B.S.eee. please read the ignorance, below....

thank you, Terry S. Singeltary Sr., Bacliff, Texas USA

Subject: 09-018 - gsc - flounder@wt.net - concern of CJD transmission with trial contact lenses Date: Fri, 06 Oct 2000 14:49:24 -0400 From: "Clark, Geoffrey S." To: "'flounder@wt.net'" CC: "Warburton, Karen" , "CDRH Small Manu. Assistance"

Terry S. Singeltary Sr.:

I have discussed your concerns with our Device Evaluation staff who have provided the following information:

The risk of CJD transmission through the use of trial (fitting) contact lenses is extremely low and at present unmeasureable. There have been no documented cases of CJD transmission via a contact lens or contact lens solution. It is highly unlikely that the CJD agent would be present on the surface of the cornea or present in the tears of an infected person. Additionally, the use of trial lens sets has been declining in the US over the past 10 years as the soft contact lens market has shifted to lenses dispensed in non-reusable blister packs. Therefore, a formal recommendation against the use of trial lenses because of potential CJD transmission is not appropriate at this time.

Please feel free to contact me if I can be of additional assistance.

=<:"Geoff Clark gsc@cdrh.fda.gov from PC 5074275; Room 130H <> (HFZ-220) 1350 Piccard Dr., Rockville, MD 20850-4307 800.638.2041x122 fax.301.443.8818 =========================================================================

From: Winston, F. Blix Sent: Tuesday, September 05, 2000 5:00 PM To: Clark, Geoffrey S. Subject: 09-018 - flounder@wt.net Geoff,

This came into the DSMA account. Would you please respond?

Thanks, Blix

-----Original Message----- From: WEBO@CDRH.FDA.GOV [SMTP:WEBO@CDRH.FDA.GOV]

Sent: Friday, September 01, 2000 9:27 AM To: DSMA@CDRH.FDA.GOV Subject: DSMA Email Form Response

Name: Terry S. Singeltary Sr. Phone Number: Na Fax Number: Na Email Address: flounder@wt.net Mailing Address: P.O. Box 42 Bacliff, Texas USA 77518

Questions/Comments: P990072 *In relation to human Transmissible Spongiform Encephalopathy and Contact Lens

i think it would be to everyone's best interest, "IF" the practice of "RE-USING" _display_ contact lens in the commercial aspect takes place in the U.S., this practice must be stopped. Please allow me to explain. In the U.K., the practice of having display of different colors of contact lens on display, for the consumer to try on, and see how they look with the different colors. These contact lens were then re-used over and over. No standard cleaning cleaning solution and or auto-claving procedure will kill the TSE agent. This is known fact. Plus, the U.K. has 'BANNED' this practice due to vCJD and sCJD (if i am not mistaken), but regardless, both can transmit the TSE agent. I will not waste my time trying to explain this in this box, will post a few URLS and you will see what i speak of if you care. But the eyes, brain, pituitary are the most infectious parts, of an infective species. Trust me, i know what i speak of.......

thank you, Terry S. Singeltary SR. ======================= ISSUE 1490

Thursday 24 June 1999

CJD alert over contact lenses By David Brown, Agriculture Editor

PEOPLE risk catching the human form of mad cow disease from re-used contact lenses, scientists warned the Government yesterday. They urged the Department of Health to stop opticians re-using trial lenses among their clients to help prevent further outbreaks of the new variant Creutzfeldt-Jakob disease which has killed 41 people so far.

The warning came from the Spongiform Encephalopathies Advisory Committee, the independent team of scientists advising the Government on BSE and CJD. Ministers are expected to ban the re-use of these lenses as a precaution, which could mean higher prices for consumers.

In a statement, the committee said: "Any potential risk is probably very low, but the committee felt strongly that the Department of Health should encourage opticians to adopt, as a matter of best practice, the single use of trial lenses followed by safe disposal." Sir John Pattison, the committee's chairman, said it was surprised to learn that it was common practice among opticians to try the same contact lenses on several clients.

It was known that the classical variety of CJD, the kind which was known before the new variant (vCJD) was announced in 1996 and linked to BSE, had been spread in the past by transplants of infected corneas.

The committee noted that the eyes are directly connected to the brain, the main seat of BSE and CJD. The warning applied to vCJD and the classical variety of the fatal brain disease.

http://www.telegraph.co.uk:80/et?ac=003588399104365&rtmo=0iJRs00q&atmo=tttttttd&pg=/et/99/6/24/ncjd24.html

Testimony of Bess Believeaux, Lions Eye Bank of Central Texas (Submission to the Jan. 18/19 meeting of the TSE Advisory Committee)

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_16.pdf


TSS Submission to the same Committee;

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf


Tissue Banks International (TBI), Gerald J Cole

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_13.pdf



"1st", i wrote this in Nov. 1999, came through BSE-L, then tom posted; Cadaver corneal transplants -- without family permission...

http://www.mad-cow.org/~tom/dec99_news.html#bbb


then JAMA came out with this on Dec. 15, 1999 from some doctor in dallas??? just a coincidence???

Preventing Prion Transmission in Corneal Transplants

http://jama.ama-assn.org/issues/v282n23/ffull/jlt1215-5.html



WE must not forget the obvious;

BEFORE going further, this has always disturbed me, please read carefully, 3 important factors to think about before using Xenotransplantation Products;

1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8 Related Articles, Links

Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

PMID: 8006664

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract


We describe the second patient with hGH related CJD in the Netherlands. The patient developed the disease 38 years after hGH injections. To our knowledge, this is the longest incubation period described for any form of iatrogenic CJD. Further-more, our patient was not treated with hGH but only received a __low dose__ as part of a __diagnostic procedure__.

Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone.

Croes EA, Roks G, Jansen GH, Nijssen PC, van Duijn CM.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12023427&dopt=Abstract


1: EMBO J 2002 Dec 2;21(23):6358-66

BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein.

Asante EA, Linehan JM, Desbruslais M, Joiner S, Gowland I, Wood AL, Welch J, Hill AF, Lloyd SE, Wadsworth JD, Collinge J.

MRC Prion Unit, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK.

Variant Creutzfeldt-Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrP(Sc) type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.

PMID: 12456643

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12456643&dopt=Abstract


PERSONAL COMMUNICATION;

Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD Date: Thu, 28 Nov 2002 10:23:43 -0000 From: "Asante, Emmanuel A" To: "'flounder@wt.net'"

Dear Terry,

I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention. Thank you for your interest in the paper.

In respect of your first question, the simple answer is, yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD.

It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.

I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.

Emmanuel Asante

<> ____________________________________

Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 ===========================

a person can look perfectly healthy but still pass the agent;

SUB-CLINICAL TSEs

MRC-43-00 Text only version of this sitePrint this page Issued: Monday, 28 August 2000 NEW EVIDENCE OF SUB-CLINICAL PRION INFECTION: IMPORTANT RESEARCH FINDINGS RELEVANT TO CJD AND BSE

A team of researchers led by Professor John Collinge at the Medical Research Council Prion Unit1 report today in the Proceedings of the National Academy of Sciences, on new evidence for the existence of a ‘sub-clinical’ form of BSE in mice which was unknown until now.

The scientists took a closer look at what is known as the ‘species barrier’ - the main protective factor which limits the ability of prions2 to jump from one species to infect another. They found the mice had a ‘sub-clinical’ form of disease where they carried high levels of infectivity but did not develop the clinical disease during their normal lifespan. The idea that individuals can carry a disease and show no clinical symptoms is not new. It is commonly seen in conventional infectious diseases.

Researchers tried to infect laboratory mice with hamster prions3 called Sc237 and found that the mice showed no apparent signs of disease. However, on closer inspection they found that the mice had high levels of mouse prions in their brains. This was surprising because it has always been assumed that hamster prions could not cause the disease in mice, even when injected directly into the brain.

In addition the researchers showed that this new sub-clinical infection could be easily passed on when injected into healthy mice and hamsters.

The height of the species barrier varies widely between different combinations of animals and also varies with the type or strain of prions. While some barriers are quite small (for instance BSE easily infects mice), other combinations of strain and species show a seemingly impenetrable barrier. Traditionally, the particular barrier studied here was assumed to be robust.

Professor John Collinge said: "These results have a number of important implications. They suggest that we should re-think how we measure species barriers in the laboratory, and that we should not assume that just because one species appears resistant to a strain of prions they have been exposed to, that they do not silently carry the infection. This research raises the possibility, which has been mentioned before, that apparently healthy cattle could harbour, but never show signs of, BSE.

"This is a timely and unexpected result, increasing what we know about prion disease. These new findings have important implications for those researching prion disease, those responsible for preventing infected material getting into the food chain and for those considering how best to safeguard health and reduce the risk that theoretically, prion disease could be contracted through medical and surgical procedures."

ISSUED FRIDAY 25 AUGUST UNDER EMBARGO. PLEASE NOTE THAT THE EMBARGO IS SET BY THE JOURNAL.

FOR FURTHER INFORMATION CONTACT THE MRC PRESS OFFICE ON 020 7637 6011 (OFFICE HOURS) OR 07818 428297 OR 0385 774357 (OUT-OF-OFFICE-HOURS) OR PROFESSOR JOHN COLLINGE ON 020 7594 3760. PLEASE NOTE THAT OWING TO TRAVEL COMMITMENTS PROFESSOR COLLINGE WILL ONLY BE AVAILABLE UNTIL 16.30 ON FRIDAY 25 AUGUST AND CONTACTABLE AGAIN ON MONDAY 28 AUGUST VIA THE MRC PRESS OFFICE. DR ANDREW HILL (A CO-AUTHOR ON THE PAPER) FROM THE DEPARTMENT OF PATHOLOGY AT THE UNIVERSITY OF MELBOURNE WILL BE AVAILABLE ON 00 61 3 8344 3995 (DURING OFFICE HOURS) OR 00 61 3 9443 0009 (OUT-OF-OFFICE HOURS). PLEASE NOTE THAT AUSTRALIA IS TEN HOURS AHEAD OF UK TIME.

NOTES FOR EDITORS

Professor Collinge is a consultant neurologist and Director of the newly formed MRC Prion Unit based at The Imperial College School of Medicine at St Mary’s Hospital. He is also a member of the UK Government’s Spongiform Encephalopathy Advisory Committee (SEAC). The MRC prion unit is was set up in 1999, and its work includes molecular genetic studies of human prion disease and transgenic modelling of human prion diseases.

Prions are unique infectious agents that cause fatal brain diseases such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie and BSE (mad cow disease) in animals. In some circumstances prions from one species of animals can infect another and it is clear that BSE has done this to cause the disease variant CJD in the UK and France. It remains unclear how large an epidemic of variant CJD will occur over the years ahead.

The strain of prion used here to infect the mice is the Sc237 strain (also known as 263K) which infects hamsters, and until now was assumed not to infect mice.

This research was funded by the Medical Research Council and Wellcome Trust.

The Medical Research Council (MRC) is a national organisation funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK. About half of the MRC’s expenditure of £345 million is invested in over 50 of its Institutes and Units, where it employs its own research staff. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools.

The Wellcome Trust is the world's largest medical research charity with a spend of some £600 million in the current financial year 1999/2000. The Wellcome Trust supports more than 5,000 researchers, at 400 locations, in 42 different countries to promote and foster research with the aim of improving human and animal health. As well as funding major initiatives in the public understanding of science, the Wellcome Trust is the country's leading supporter of research into the history of medicine.

©2002 Medical Research Council

http://www.mrc.ac.uk/

Views & Reviews Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States Ermias D. Belay, MD, Ryan A. Maddox, MPH, Pierluigi Gambetti, MD and Lawrence B. Schonberger, MD

From the Division of Viral and Rickettsial Diseases (Drs. Belay and Schonberger and R.A. Maddox), National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA; and National Prion Disease Pathology Surveillance Center (Dr. Gambetti), Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH.

Address correspondence and reprint requests to Dr. Ermias D. Belay, 1600 Clifton Road, Mailstop A-39, Atlanta, GA 30333.

Transmissible spongiform encephalopathies (TSEs) attracted increased attention in the mid-1980s because of the emergence among UK cattle of bovine spongiform encephalopathy (BSE), which has been shown to be transmitted to humans, causing a variant form of Creutzfeldt-Jakob disease (vCJD). The BSE outbreak has been reported in 19 European countries, Israel, and Japan, and human cases have so far been identified in four European countries, and more recently in a Canadian resident and a US resident who each lived in Britain during the BSE outbreak. To monitor the occurrence of emerging forms of CJD, such as vCJD, in the United States, the Centers for Disease Control and Prevention has been conducting surveillance for human TSEs through several mechanisms, including the establishment of the National Prion Disease Pathology Surveillance Center. Physicians are encouraged to maintain a high index of suspicion for vCJD and use the free services of the pathology center to assess the neuropathology of clinically diagnosed and suspected cases of CJD or other TSEs.

Post-Publication Peer Reviews:

Read all Post-Publication Peer Reviews

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States Terry S. Singeltary Neurology Online, 27 Jan 2003 [Full text]

http://www.neurology.org/cgi/eletters/60/2/176#535


Reply to Singletary Ryan A. Maddox, MPH, et al. Neurology Online, 26 Mar 2003 [Full text]

http://www.neurology.org/cgi/eletters/60/2/176#582




Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734.

Full Text

Tue, 13 Feb 2001 JAMA Vol. 285 No. 6, February 14, 2001 Letters

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

To the Editor:

In their Research Letter in JAMA. 2000;284:2322-2323, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex

To the Editor:

At the time of my mother's death, various diagnoses were advanced such as "rapid progressive Alzheimer disease," psychosis, and dementia. Had I not persisted and personally sought and arranged a brain autopsy, her death certificate would have read cardiac failure and not CJD.

Through CJD Voice1 I have corresponded with hundreds of grief-stricken families who are so devastated by this horrific disease that brain autopsy is the furthest thing from their minds. In my experience, very few physicians suggest it to the family. After the death and when families reflect that they never were sure what killed their loved one it is too late to find the true cause of death. In the years since my mother died I think that the increasing awareness of the nature of CJD has only resulted in fewer pathologists being willing to perform an autopsy in a suspected case of CJD.

People with CJD may die with incorrect diagnoses of dementia, psychosis, Alzheimer disease, and myriad other neurological diseases. The true cause of death will only be known if brain autopsies are suggested to the families. Too often the physician's comment is, "Well, it could be CJD but that is so rare it isn't likely."

Until CJD is required to be reported to state health departments, as other diseases are, there will be no accurate count of CJD deaths in the United States and thus no way to know if the number of deaths is decreasing, stable, or increasing as it has recently in the United Kingdom.

Dorothy E. Kraemer Stillwater, Okla

In Reply:

Mr Singeltary and Ms Kraemer express an underlying concern that our recently reported mortality surveillance estimate of about 1 CJD case per million population per year in the United States since 1985 may greatly underestimate the true incidence of this disease. Based on evidence from epidemiologic investigations both within and outside the United States, we believe that these national estimates are reasonably accurate.

Even during the 1990s in the United Kingdom, where much attention and public health resources have been devoted to prion disease surveillance, the reported incidence of classic CJD is similar to that reported in the United States.

In addition, in 1996, active US surveillance for CJD and new variant (nv) CJD in 5 sites detected no evidence of the occurrence of nvCJD and showed that 86% of the CJD cases in these sites were identifiable through routinely collected mortality data.

Our report provides additional evidence against the occurrence of nvCJD in the United States based on national mortality data analyses and enhanced surveillance. It specifically mentions a new center for improved pathology surveillance. We hope that the described enhancements along with the observations of Singeltary and Kraemer will encourage medical care providers to suggest brain autopsies for more suspected CJD cases to facilitate the identification of potentially misdiagnosed CJD cases and to help monitor the possible occurrence of nvCJD.

Creutzfeldt-Jakob disease is not on the list of nationally notifiable diseases. In those states where surveillance personnel indicate that making this disease officially notifiable would meaningfully facilitate collection of data that are needed to monitor the incidence of CJD and nvCJD, including the obtaining of brain autopsy results, we encourage such a change. However, adding CJD to the notifiable diseases surveillance system may lead to potentially wasteful, duplicative reporting because the vast majority of the diagnosed cases would also be reported through the mortality surveillance system.

Furthermore, making CJD a notifiable disease may not necessarily help identify undiagnosed CJD cases. The unique characteristics of CJD make mortality data a useful surrogate for ongoing surveillance. Unlike many other neurologic diseases, CJD is invariably fatal and in most cases rapidly progressive and distinguishable clinically from other neurologic diseases.

Because CJD is least accurately diagnosed early in the course of the illness, notifiable disease surveillance of CJD could be less accurate than mortality surveillance of CJD. In addition, because death as a condition is more completely and consistently reported, mortality surveillance has the advantage of being ongoing and readily available.

The absence of CJD and nvCJD from the list of nationally notifiable diseases should not be interpreted to mean that they are not important to public health; this list does not include all such diseases. We encourage medical caregivers to report to or consult with appropriate public health authorities about any diagnosed case of a transmissible disease for which a special public health response may be needed, including nvCJD, and any patient in whom iatrogenic transmission of CJD may be suspected.

Robert V. Gibbons, MD, MPH Robert C. Holman, MS Ermias D. Belay, MD Lawrence B. Schonberger, MD, MPH Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, Ga

http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=dignosing+and+reporting+creutzfeldt+jakob+disease&searchid=1048865596978_1528&stored_search=&FIRSTINDEX=0&journalcode=jama


SOMETHING TO CHEW ON

BMJ

http://www.bmj.com/cgi/eletters/319/7220/1312/b#EL2


BMJ

http://www.bmj.com/cgi/eletters/320/7226/8/b#EL1


My Submission will be on the 'slides' of the Jan. 19, meeting...tss

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2.htm


PDF]Freas, William TSS SUBMISSION File Format: PDF/Adobe Acrobat - Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary Sr. [flounder@wt.net] Monday, January 08,200l 3:03 PM freas ...

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf

Transmissible Spongiform Encephalopathy Advisory Committee February 20, 2003 (SLIDES)

http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm


EPA Comment Number: 550-2 Received: October 26, 1998 Subject: DOCKET # opp-00550 FEDERAL FOOD AND SAFETY PLAN!!!

http://www.epa.gov/oppts/documents/550-2.pdf


Docket No: 01-064-1 Title: Animal Disease Risk Assessment, Prevention, and Control Act Contact Person: Mr. William Macheel, (301) 734-4420 Comments Due: October 9, 2001 Received on E-comments 24. Terry S. Singeltary Sr. 8/22/01

http://www.aphis.usda.gov/ppd/rad/LPOC/01-064-1.txt





GERMAN DER SPIEGEL MAGAZINE

http://www.spiegel.de/spiegel/0,1518,119306,00.html

also;

NEW SCIENTIST MAGAZINE 4/02/01

NEW SCIENTIST EDITORIAL PAGE 3

MAD SHEEP DISEASE?

IF THERE is one categorical pronouncement you can safely make about prion diseases like BSE or CJD, it is that one should not make categorical pronouncements. "British beef is safe" and "there is no BSE in Germany" come to mind. Now there are two more: "scrapie is safe", and "people don't catch sporadic CJD". Scrapie is the most widespread prion disease, infecting untold numbers of sheep worldwide. Sporadic CJD is the old-fashioned pre-BSE kind that is supposed to happen spontaneously in unlucky people. But a surprise observation in France suggests some sCJD cases--though by no means all--may be linked to scrapie after all (see p 4).

For years, British authorities asserted that BSE was harmless because it was a form of scrapie. In fact, the only evidence scrapie is safe is some broad-brush epidemiology, good as far as it goes but unable to reveal occasional risks for some people from some sheep. Alarm bells should have rung in 1980 when researchers gave monkeys scrapie by feeding them infected brains. But that research, like so much other work on prion diseases, was never followed up. We still have little idea what BSE does in pigs and chickens. The Queniborough vCJD outbreak (see p 5) would be easier to understand if we knew how much brain we must eat to be infected. As for scrapie, it shouldn't take a chance finding to tell us that there may be dangerous sheep out there.

Suspect symptoms

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

Exclusive from New Scientist magazine

Four years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease.................

full text url follows By Debora MacKenzie

Suspect Symptoms

http://www.newscientist.com/hottopics/bse/suspectsymptoms.jsp

if url dead, go here for 'SUSPECT SYMPTOMS'

you can access article here also;

http://www.organicconsumers.org/meat/scrapiecjd.cfm



Then follow up with PNAS studies from which new scientist article written from;

Published online before print March 20, 2001 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.041490898

Neurobiology Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt- Jakob disease: Implications for human health Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp [Dagger ] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [] , Dominique Dormont*, and Jean-Philippe Deslys*

* Commissariat à l'Energie Atomique, Service de Neurovirologie, Direction des Sciences du Vivant/Département de Recherche Medicale, Centre de Recherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc, BP 6, 92 265 Fontenay-aux-Roses Cedex, France; [Dagger ] Hôpital Neurologique Pierre Wertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and [] Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, United Kingdom

Edited by D. Carleton Gajdusek, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France, and approved December 7, 2000 (received for review October 16, 2000)

Abstract

There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt-Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.

Introduction

The recognition of a variant of the human transmissible spongiform encephalopathy (TSE) Creutzfeldt-Jakob Disease (vCJD) in the U.K. in 1996 raised the major concern that it would correspond to human infection with the agent responsible for bovine spongiform encephalopathy (BSE; ref. 1). Transmission of BSE to macaques provided the first experimental evidence as it produced a disease close to vCJD in humans (2). Strain typing in inbred mice (consisting of measuring the incubation period and establishing lesion profiles corresponding to the strain-specific distribution of brain vacuolation) allows reliable identification of TSE strains (3). This method, together with biochemical methods, has revealed a single phenotype for the agents of BSE and the British cases of vCJD (4-6). Mice expressing only the bovine prion protein (PrP) were highly susceptible to vCJD and BSE, which induced the same disease (7). Thus, it is now well established that BSE has caused vCJD, probably by alimentary contamination. In this respect, the finding of abnormal PrP labeling in the gastrointestinal tract and lymphatic tissues of orally BSE-contaminated lemurs shows that the BSE agent can infect primates by the oral route (8). About 1 million contaminated cattle may have entered the human food chain, and the future number of vCJD cases could range from 63 to 136,000 depending on the incubation period of BSE in humans (9). Unlike sporadic CJD (sCJD) and iatrogenic CJD (iCJD) linked to the administration of contaminated growth hormone extracted from human hypophyses, in vCJD, the infectious agent seems to be widely distributed in lymphoid organs, as pathological PrP (PrPres) can be detected in tonsils, lymph nodes, spleen, and appendix even in the preclinical phase of the disease (10, 11). This raises a public health issue with regard to the risk of iatrogenic transmission of vCJD through surgical instruments, grafts, blood transfusion, or parenteral administration of biological products of human origin. However, this risk is difficult to assess, because it largely depends on factors such as the virulence of the BSE agent adapted to primates and the efficiency of secondary transmission to humans by a peripheral route such as the i.v. one. A further issue is whether vCJD accidentally acquired from humans would be recognized. The latter poses the question of a phenotypic variation of the BSE agent after successive transmissions in humans: does it retain its strain characteristics, and does it induce a pathology similar to that observed in the previous host? A 9-year history of transmission of BSE to primates and mice enables us today to clarify a number of these important points.

Although BSE has mainly affected the U.K., two definite cases and one probable case of vCJD have now been reported in France in people who have never resided in the U.K. (12, 13). We strain-typed the first of these cases to establish its origin. Strain typing in C57BL/6 mice of BSE, French, and British vCJD was compared with that of BSE passaged in nonhuman primates, thus allowing us to study the effect of serial passages in primates. Comparisons were also made with French cases of sCJD and iCJD and two strains of scrapie (one of French and one of U.S. origin). Our findings provide experimental demonstration that the same agent, namely that responsible for the cattle disease BSE, has caused vCJD both in France and in the U.K., in line with biochemical data and with the fact that, until 1996, about 10% of the beef consumed in France was imported from the U.K. We found that the BSE agent in nonhuman primates is similar to that causing vCJD in humans and tends to evolve rapidly toward a primate-adapted variant. Furthermore, we showed that the strain responsible for iCJD is closely related to that of one patient with sCJD, and, more unexpectedly, that these agents were similar to the French scrapie strain studied (but different from the U.S. scrapie strain). This finding requires a cautious interpretation for several reasons, not least because of the inevitably limited number of TSE strains that can be studied by such a cumbersome method as strain typing. Nonetheless, it also prompts reconsideration of the possibility that, in some instances, sheep and human TSEs can share a common origin.

snip...

http://www.pnas.org/cgi/content/full/041490898v1


STATEMENT OF DR HELEN GRANT MD FRCP ISSUED 13/05/1999

BSE INQUIRY

http://www.bseinquiry.gov.uk/files/ws/s410.pdf

http://www.bseinquiry.gov.uk/files/ws/s410x.pdf


http://www.bseinquiry.gov.uk/evidence/ws/ws8.htm


CWD to CJD in humans (why not?), as easy as BSE/Scrapie;

The EMBO Journal, Vol. 19, No. 17 pp. 4425-4430, 2000 © European Molecular Biology Organization

Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease

G.J. Raymond1, A. Bossers2, L.D. Raymond1, K.I. O?Rourke3, L.E. McHolland4, P.K. Bryant III4, M.W. Miller5, E.S. Williams6, M. Smits2 and B. Caughey1,7

1NIAID/NIH Rocky Mountain Laboratories, Hamilton, MT 59840, 3USDA/ARS/ADRU, Pullman, WA 99164-7030, 4USDA/ARS/ABADRL, Laramie, WY 82071, 5Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, CO 80526-2097, 6Department of Veterinary Sciences, University of Wyoming, Laramie, WY 82070, USA and 2ID-Lelystad, Institute for Animal Science and Health, Lelystad, The Netherlands 7Corresponding author e-mail: bcaughey@nih.gov Received June 7, 2000; revised July 3, 2000; accepted July 5, 2000.

Abstract

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and elk, and little is known about its transmissibility to other species. An important factor controlling interspecies TSE susceptibility is prion protein (PrP) homology between the source and recipient species/genotypes. Furthermore, the efficiency with which the protease-resistant PrP (PrP-res) of one species induces the in vitro conversion of the normal PrP (PrP-sen) of another species to the protease-resistant state correlates with the cross-species transmissibility of TSE agents. Here we show that the CWD-associated PrP-res (PrPCWD) of cervids readily induces the conversion of recombinant cervid PrP-sen molecules to the protease-resistant state in accordance with the known transmissibility of CWD between cervids. In contrast, PrPCWD-induced conversions of human and bovine PrP-sen were much less efficient, and conversion of ovine PrP-sen was intermediate. These results demonstrate a barrier at the molecular level that should limit the susceptibility of these non-cervid species to CWD.

snip...

Clearly, it is premature to draw firm conclusions about CWD passing naturally into humans, cattle and sheep, but the present results suggest that CWD transmissions to humans would be as limited by PrP incompatibility as transmissions of BSE or sheep scrapie to humans. Although there is no evidence that sheep scrapie has affected humans, it is likely that BSE has caused variant CJD in 74 people (definite and probable variant CJD cases to date according to the UK CJD Surveillance Unit). Given the presumably large number of people exposed to BSE infectivity, the susceptibility of humans may still be very low compared with cattle, which would be consistent with the relatively inefficient conversion of human PrP-sen by PrPBSE. Nonetheless, since humans have apparently been infected by BSE, it would seem prudent to take reasonable measures to limit exposure of humans (as well as sheep and cattle) to CWD infectivity as has been recommended for other animal TSEs.

snip...

http://www.emboj.org/current.shtml


Scrapie to Humans?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3915057&dopt=Abstract


Houston Chronicle article Aug. 5, 2001

MAD COW DISEASE: Could It Happen Here?

'ARCHIVED'

http://www.chron.com/cs/CDA/story.hts/metropolitan/991714


go here for chronicle article;

http://www.organicconsumers.org/madcow/crusade8501.cfm



Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 CJD WATCH ==========

[Federal Register: April 4, 2003 (Volume 68, Number 65)] [Notices] [Page 16520-16522] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr04ap03-80]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 03D-0118]

Guidance for FDA Staff on Sampling or Detention Without Physical Examination of Decorative Contact Lenses (Import Alert 86-10); Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a guidance document entitled ``Guidance for FDA Staff on Sampling or Detention Without Physical Examination of Decorative Contact Lenses (Import Alert 86-10).'' The guidance document includes FDA's guidance to FDA district offices for sampling or detention without physical examination of plano (zero-powered or noncorrective) contact lenses intended solely to change the appearance of the normal eye in decorative fashion, when these products are presented for importation into the United States.

DATES: Submit written or electronic comments on the guidance by June 3, 2003.

ADDRESSES: Submit written requests for single copies of the Import Alert 86-10, to the Division of Import Operations and Policy (HFC-170), Office of Regulatory Affairs, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Send two self-addressed adhesive labels to assist that office in processing your request. You may fax your request to 301-594-0413. Submit written comments on this guidance to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments. See the SUPPLEMENTARY INFORMATION section for information on electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Thaddeus J. Poplawski, Division of Import Operations and Policy (HFC-170), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-443-6553.

SUPPLEMENTARY INFORMATION:

I. Background

FDA has been receiving reports that certain commercial entities are planning to distribute or may already be distributing plano (zero- powered or noncorrective) contact lenses intended solely to change the normal appearance of the eye in decorative fashion (decorative contact lenses). FDA understands that these products are intended to be distributed without a prescription, without fitting by a qualified eye care professional, and without ongoing professional supervision. FDA believes that, like other contact lenses, decorative contact lenses can cause a variety of eye injuries and conditions. Lens wear has been associated with corneal ulcer, for example, which can progress rapidly, leading to internal ocular infection if left untreated. Uncontrolled infection

[[Page 16521]]

can lead to corneal scarring, which can lead to vision impairment. In extreme cases, corneal ulcer can result in blindness and eye loss. Other risks include conjunctivitis; corneal edema; allergic reaction; abrasion from poor lens fit; and reduction in visual acuity, contrast sensitivity, and other visual functions, resulting in interference with driving and other activities. FDA believes that these risks cannot be sufficiently controlled unless: (1) The wearer obtains advice from an eye care professional; (2) the lenses are fitted by or under the supervision of such a professional; and (3) the wearer remains under appropriate professional supervision. Eye care professional involvement is legally required (21 CFR 801.109) for contact lenses intended for medical purposes (i.e., prosthetic use or vision correction). These products are regulated by FDA as medical devices under the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301 et seq.). \1\ Such control is not available for decorative contact lenses because these products are cosmetics under section 201(i) of the act (21 U.S.C. 321(i)). ---------------------------------------------------------------------------

\1\There are some lenses currently on the market under cleared 510(k)s covering contact lenses intended for both vision correction use and for solely decorative purposes.The sponsors in these cases voluntarily included a plano lens in the range of corrective powers described in the 510(k) submissions. ---------------------------------------------------------------------------

Section 201(i) of the act defines ``cosmetic'' to include ``articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance * * * '' (21 U.S.C. 321(i)(1)). Decorative contact lenses are articles intended to be introduced into the eye, which is a part of the body, to beautify the wearer, promote the attractiveness of the wearer, or alter the wearer's appearance. They are claimed to achieve this cosmetic result by changing the apparent color of the iris; by appearing to add a design to the iris (e.g., a professional sports team insignia); or by imparting a nonhuman or otherwise nonnormal appearance to the eye (e.g., cat's eye). Provided they are not marketed with claims\2\ that they effect physical or physiological change, decorative contact lenses are properly regulated as cosmetics under the act (cf. United States v. An Article * * * ``Sudden Change,'' 409 F.2d 734 (2d Cir. 1969) (``claiming to affect the structure of the skin in some physiological way'' makes a product a ``drug''); 21 CFR 700.35 (``sunscreen'' claims make a product a drug)). ---------------------------------------------------------------------------

\2\American Health Prods Co. v. Hayes, 574 F. Supp. 1498, 1505 (S.D.N.Y. 1983), aff'd on other grounds, 744 F.2d 912 (2d Cir. 1984) (The courts ``have always read the * * * statuatory definitions employing the term `intended' to refer to specific marketing representations.''). ---------------------------------------------------------------------------

The fact that contact lenses are ``devices'' in the colloquial sense does not preclude cosmetic status under the act. FDA has previously determined that section 201(i) of the act applies to appearance-enhancing devices such as wigs, hair brushes, stockings and toothpicks (Refs. 1 through 3). Moreover, the fact that a product is intended to come into contact with the eye does not make it ineligible for cosmetic regulation (Ref. 4). Indeed, the legislative history accompanying the original 1938 act demonstrates that Congress enacted the cosmetic adulteration provisions to address the risk to users presented by cosmetic products that may cause blindness and other serious injuries (S. Rept. 74-361 at 21 (1935)). On October 22, 2002, FDA issued Import Alert 86-10, with respect to decorative contact lenses. We are now publishing a revised Import Alert 86-10 in the Federal Register. The Import Alert 86-10 does not cover contact lenses that are intended for vision correction or for prosthetic or other medical use. Section 801(a) of the act (21 U.S.C. 381(a)) authorizes FDA to refuse admission to articles that appear to be adulterated or misbranded. Based on the available evidence, FDA believes that decorative contact lenses presented for importation may appear to be adulterated under section 601(a) of the act (21 U.S.C. 361(a)), in that they contain a deleterious substance that is dangerous to wearers of the lenses when they are put to a labeled, customary, or usual use. The deleterious substance is the matrix in which colorants are embedded. This material can cause the potentially vision-threatening eye conditions discussed previously, particularly if the wearer fails to obtain appropriate professional counseling, fitting, and ongoing supervision; if the wearer trades lenses, fails to use proper disinfection and other care techniques; or if the wearer wears lenses for longer than the recommended period. Consequently, FDA believes that decorative contact lenses appear to be adulterated under section 601(a). Decorative contact lenses may also be subject to refusal if they appear to contain unsafe color additives (21 U.S.C. 381(a) and 361(e)). FDA understands that certain overseas manufacturers or distributors might have selected color additives for use in decorative contact lenses intended for U.S. distribution based on the fact that they have been approved by FDA for use in medical devices. To be used lawfully in decorative contact lenses, a color additive must be approved by FDA for use in eye area cosmetics. Not all color additives approved for use in medical devices have been approved for eye area use in cosmetics. Consequently, decorative contact lenses may also appear to be adulterated under section 601(e) of the act. Finally, decorative contact lenses may be subject to refusal on the ground that they are misbranded under section 602(a) of the act (21 U.S.C. 362(a)) because their labeling is false or misleading ``in any particular.'' Under the act, labeling can be misleading by failing to disclose ``facts * * * material with respect to consequences which may result'' from use of a product under customary, usual, or labeled conditions (21 U.S.C. 321(n)). As noted previously, decorative contact lenses may cause serious health problems, including (in extreme cases) blindness. FDA believes these risks are material. If they are not disclosed in labeling, then the labeling would be misleading, and the product would appear to be misbranded under section 602(a) of the act and subject to refusal under section 801(a) of the act.

II. Guidance

FDA's district offices may sample or detain without physical examination decorative contact lenses presented for U.S. importation. The Import Alert 86-10 applies to contact lenses that are: (1) Intended to change the appearance of the normal eye in decorative fashion; and (2) intended for distribution directly to the wearer, without the involvement of a qualified eye care professional. It does not cover contact lenses that are intended for vision correction or for prosthetic or other medical or therapeutic use and that are, therefore, properly regulated as medical devices under the act.

III. Significance of Guidance

This level 1 guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the agency's current thinking on the sampling or detention without physical examination of decorative contact lenses that appear to be adulterated under section 601(a) and (e) of the act because they contain a deleterious substance that is harmful to users and/or contain an unapproved color additive, or appear to be misbranded under section 602(a) because their labeling is false or misleading. It does not create or confer

[[Page 16522]]

any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the applicable statute and regulations. This guidance is effective immediately because prior public participation is not feasible or appropriate due to the risks to the public health presented by these products.

IV. Comments

Interested persons may submit to the Dockets Management Branch (see ADDRESSES) written or electronic comments regarding this guidance. Such comments will be considered when determining whether to amend the current guidance. Two paper copies of any mailed comments are to be submitted, except that individuals may submit one paper copy. Comments are to be identified with the docket number found in brackets in the heading of this document. The guidance and received comments are available in the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through Friday.

V. Electronic Access

Persons with access to the Internet may obtain the guidance at http://www.fda.gov/ora/fiars/ora_import_ia8610.html.

VI. References

The following references have been placed on display in the Dockets Management Branch (see ADDRESSES) and may be seen by interested persons between 9 a.m. and 4 p.m., Monday through Friday. 1. Food and Drug Administration (FDA), Compliance Policy Guide (CPG) 7128.04 (revised August 1996) (hair brushes); (http://www.fda.gov/ora/compliance_ref/cpg/cpgfod/cpg590-400.htm ). 2. FDA, CPG 7128.05 (revised September 1, 1986) (wigs); (http://www.fda.gov/ora/compliance_ref/cpg/cpgfod/cpg590-600.htm ). 3. Hutt, Peter Barton, ``Reconciling the Legal, Medical, and Cosmetic Chemist Approach to the Definition of a `Cosmetic,' '' Cosmetic, Toiletry, and Fragrance Association Cosmetic Journal'', vol. 3, 1971 (excerpted in Peter Barton Hutt & Richard A. Merrill, Food and Drug Law: Cases and Materials, p. 824-825 (2d ed. 1991)). 4. FDA, CPG 7128.03 (revised August 1996) (mascara is an eye- contact cosmetic); (http://www.fda.gov/ora/compliance_ref/cpg/cpgfod/cpg590-300.htm ).

Dated: April 1, 2003. John R. Marzilli, Acting, Associate Commissioner for Regulatory Affairs. [FR Doc. 03-8315 Filed 4-2-03; 11:42 am]

BILLING CODE 4160-01-S

http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2003/03-8315.htm


TSS

END




>>> "the biochemical signature of PrPres in the BASE-inoculated animal was
found to have a higher proteinase K sensitivity of the octa-repeat
region. We found the same biochemical signature in three of four human
patients with sporadic CJD and an MM type 2 PrP genotype who lived in
the same country as the infected bovine." <<< http://bse-atypical.blogspot.com/2008/08/atypical-bse-base-transmitted-from.html


NOT to forget ;

Thursday, June 05, 2008 Review on the epidemiology and dynamics of BSE epidemics Vet. Res. (2008) 39:15 www.vetres.org DOI: 10.1051/vetres:2007053 c INRA, EDP Sciences, 2008 Review article

snip...

And last but not least, similarities of PrPres between Htype BSE and human prion diseases like CJD or GSS have been put forward [10], as well as between L-type BSE and CJD [17]. These findings raise questions about the origin and inter species transmission of these prion diseases that were discovered through the BSE active surveillance.

snip...

Cases of atypical BSE have only been found in countries having implemented large active surveillance programs. As of 1st September 2007, 36 cases (16 H, 20 L) have been described all over the world in cattle: Belgium (1 L) [23], Canada (1 H)15, Denmark (1 L)16, France (8 H, 6 L)17, Germany (1 H, 1 L) [13], Italy (3 L)18, Japan (1 L) [71], Netherlands (1 H, 2 L)19, Poland (1 H, 6 L)20, Sweden (1 H)21, United Kingdom (1 H)22, and USA (2 H)23. Another H-type case has been found in a 19 year old miniature zebu in a zoological park in Switzerland [56].

It is noteworthy that atypical cases have been found in countries that did not experience classical BSE so far, like Sweden, or in which only few cases of classical BSE have been found, like Canada or the USA. And last but not least, similarities of PrPres between Htype BSE and human prion diseases like CJD or GSS have been put forward [10], as well as between L-type BSE and CJD [17].

These findings raise questions about the origin and inter species transmission of these prion diseases that were discovered through the BSE active surveillance.

full text 18 pages ;

http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v07232.pdf

please see full text ;

http://bse-atypical.blogspot.com/2008/06/review-on-epidemiology-and-dynamics-of.html

***Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.***

Progress Report from the National Prion Disease Pathology Surveillance Center An Update from Stephen M. Sergay, MB, BCh & Pierluigi Gambetti, MD April 3, 2008

http://www.aan.com/news/?event=read&article_id=4397&page=72.45.45


Sunday, March 16, 2008

MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE

http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html

HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008

snip...

Tissue infectivity and strain typing of the many variants Manuscript of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...

snip...

http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html

Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate

http://organicconsumers.org/forum/index.php?showtopic=1951

http://bse-atypical.blogspot.com/2008/08/atypical-bse-base-transmitted-from.html


Creutzfeldt Jakob Disease
>
> http://creutzfeldt-jakob-disease.blogspot.com/

>
> http://creutzfeldt-jakob-disease.blogspot.com/2008/01/cjd-hgh-body-snatchers.html

>
> http://creutzfeldt-jakob-disease.blogspot.com/2008/01/tubulovesicular-structures-are.html

>
> http://creutzfeldt-jakob-disease.blogspot.com/2008/01/risk-factors-for-sporadic-creutzfeldt.html

>
> http://creutzfeldt-jakob-disease.blogspot.com/2008/01/creutzfeldt-jakob-disease-prion-protein.html

>
> http://creutzfeldt-jakob-disease.blogspot.com/2007/12/risk-assessment-of-transmission-of.html

>
> http://creutzfeldt-jakob-disease.blogspot.com/2007/12/risk-factors-for-sporadic-creutzfeldt.html

>
> http://creutzfeldt-jakob-disease.blogspot.com/2006/11/on-question-of-sporadic-or-atypical.html

>
>
>
> USA PRION UNIT BLOG
>
> http://prionunitusaupdate2008.blogspot.com/

>
>
> Sunday, April 20, 2008
>
> Progress Report from the National Prion Disease Pathology Surveillance
> Center April 3, 2008
>
> http://prionunitusaupdate2008.blogspot.com/2008/04/progress-report-from-national-prion.html

>



to be continued. ...TSS

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