Do you STILL feel safe?

[flounder]

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

CJD WATCH MESSAGE BOARD
Anonymous
Re: Possible body parts theft ring uncovered (spreading TSEs
Tue Dec 27, 2005 20:34
70.110.84.167


Update on Donor Screening
for TSEs
Melissa A. Greenwald, MD
Division of Human Tissues
Office of Cellular, Tissue and Gene Therapies
AATB 29th Annual Meeting
Hollywood, Florida
Council of Accredited Tissue Banks
Tuesday 20 September 2005
Today's talk will focus on:
• What are Transmissible Spongiform
Encephalopathies (TSEs)?
• Background on CJD/vCJD Draft
Guidance
• Specific recommended deferral criteria
• Allow time for discussion and
questions
What are TSEs?
• Human Transmissible Spongiform
Encephalopathies (TSEs) include
Creutzfeldt Jakob Disease (CJD) and
variant Creutzfeldt Jakob Disease
(vCJD)
• CJD has been a known agent, but
vCJD has only been identified in the
recent past—is a human form of
Bovine Spongiform Encephalopathy
(BSE), known as "mad cow disease"
What are TSEs? (cont.)
• The TSE agent is a prion–a poorly
understood agent; is an abnormal
protein that causes a degenerative
disease of the central nervous
system (CNS) that is not curable and
invariably leads to the death of the
person with the disease
• The agent is very difficult to destroy
and would not be inactivated by
current tissue processing technology
What are TSEs? (cont.)
• Blood from some animals
experimentally infected with TSE
agents, including the BSE agent,
contains low levels of infectivity
• Several TSE agents, including BSE,
have been experimentally
transmitted by transfusion
• Agent for vCJD is ingested, so it is
likely that the agent has a bloodborne
phase in humans (the
specifics of the pathology in humans
is poorly understood)
What are TSEs? (cont.)
• There are no published studies
showing transmission of the BSE
agent via HCT/Ps; however
• vCJD agent is present in lymph
nodes and tonsils of infected
patients
• vCJD has been transmitted via blood
transfusion in the UK
• Transmission of CJD via cornea and
dura mater has already been
demonstrated in humans
What are TSEs? (cont.)
• Because of studies showing blood
infectivity of TSE agents, it is a
theoretical risk that HCT/Ps have the
potential to transmit TSEs
• Because of this theoretical risk, FDA
is concerned about the potential for
transmission of TSEs via HCT/Ps
and therefore considers TSEs a
RCDAD and requires donor
screening for these agents
CJD/vCJD draft guidance
• Deferral of tissue donors for risk
factors for "classic" (sporadic)
CJD—already recommended in the
1997 guidance for industry
• The draft guidance for CJD/vCJD
incorporated those deferrals, and in
addition recommends deferrals for
risk factors for variant CJD—travel or
residence in BSE-affected countries
• The draft guidance published June
2002
• There was a 6 month comment
CJD/vCJD draft guidance
• Draft guidance was modeled after the
guidance for industry for blood
donors, issued August 2001
• Recommends the same countries,
dates, and lengths of
travel/residence as does the
guidance for blood donors
• Permits an exception for the
collection and storage of
hematopoietic stem cells from
donors who live in or travel to a BSEaffected
country (for urgent medical
CJD/vCJD draft guidance
• Comments reviewed at CBER
• Final recommendations for
CJD/vCJD screening will be
incorporated into the final Donor
Eligibility guidance when published
• As of May 25, 2005 Transmissible
Spongiform Encephalopathy (CJD
and vCJD) is a relevant
communicable disease agent or
disease (RCDAD) and establishments
must screen for CJD/vCJD
CJD/vCJD draft guidance
• Specific deferral criteria in the draft
guidance are an indication of FDA's
current thinking about how to
adequately and appropriately reduce
the risk of infectious disease
transmission by this agent
• Until a final guidance is issued,
establishments would not
necessarily have to "adopt" the
recommended deferral criteria but
the regulations do require some
screening for TSEs (including CJD
and vCJD)
CJD/vCJD draft guidance
• May use alternate screening criteria as long
as the screening criteria are at least as strict
as those recommended by FDA (i.e., are as
effective to adequately and appropriately
reduce the risk of infectious disease
transmission)
• No testing recommendations made—there
are no FDA approved tests for humans
CJD/vCJD Risks for Donor
Screening
• Persons who have been diagnosed
with vCJD or any other form of CJD
• Persons who have been diagnosed
with dementia or any degenerative or
demyelinating disease of the CNS or
other neurological disease of
unknown etiology [Possible that
FDA may make a distinction between
dementia and acute delirium (e.g.,
delirium caused by toxic/metabolic
disease or recent head trauma)]
Donor Screening (cont.)
• Persons who are at increased risk for CJD
– Receipt of human dura mater transplant
– Receipt of human pituitary-derived growth
hormone
– One or more blood relatives diagnosed with
CJD
• Persons who spent three months or more
cumulatively in the U.K. from the
beginning of 1980 through the end of 1996
Donor Screening (cont.)
• Persons who are current or former
U.S. military members, civilian
military employees, or dependents of
a military member or civilian
employee who resided at U.S.
military bases in Northern Europe for
6 months or more from 1980 through
1990, or elsewhere in Europe for 6
months or more from 1980 through
1996
Donor Screening (cont.)
• Persons who lived cumulatively for 5
years or more in Europe between
1980 and the present
• Persons who received any
transfusion of blood or blood
components in the U.K. between
1980 and the present
• NOTE—If the person being
interviewed is not familiar with the
term CJD, you may take that as a
negative response
The UK
• For the guidance, the UK includes
– England
– Northern Ireland
– Scotland
– Wales
– Isle of Man
– Channel Islands
– Gibraltar
– the Falkland Islands.
Military Bases
• In Northern Europe includes
– Germany, UK, Belgium, Netherlands
– Deferral from 1980-1990
• In Southern Europe includes
– Greece, Turkey, Spain, Portugal, Italy
– Deferral from 1980-1996
Family History of CJD
• Would be ineligible UNLESS:
– the diagnosis of CJD was subsequently found
to be an incorrect diagnosis;
– the CJD was iatrogenic; or
– laboratory testing (gene sequencing) shows
that the donor does not have a mutation
associated with familial CJD
For further information
http://www.fda.gov/cber/gdlns/cjdvcjd0602
.htm
Melissa Greenwald
301-827-2002
[email protected].
Vox Sang. 89(2) pp. 63-70.


http://www.fda.gov/cber/summaries/aatb092005mg.pdf



what does this week have in store for recipients of donor tissue;


PRODUCT
Acellular Dermal Matrix Skin Tissue, Recall # B-0276-6
CODE
Alloderm
B10084-002, B10084-007, B10084-009, B10084-012 thru 014, B10084-017 and 018,
B10084-023, B10084-025 thru 029, B10085-001 and 002, B10085-007 thru 012,
B10085-017, B10085-021 thru 025, B10088-001, B10088-006 thru 009, B10088-010
thru 021, B10088-025 thru 035, B10134-001 thru 004, B10134-010 and 011,
B10134-017 thru 026, B10192-007 and 008, B10192-012, B10192-016 and 017,
B10192-019, B10192-024 and 025, B10192-028 thru 035, B10222-001, B10222-005
and 006, B10222-014 and 015, B10222-017 thru 020, B10222-022 thru 024,
B10222-026, B10222-028, B10721-009 thru 012, B10721-016 thru 024, B10819-001
and 002, B10819-005 thru 007, B10819-009 thru 014, B10819-016 thru 018,
B10819-031 and 032, B10819-035, B10838-007, B10838-009, B10838-018 thru 023,
B10838-026 thru 028, B10850-001 thru 004, B10850-009 thru 016, B11021-001
and 002, B11021-008 thru 011, B11022-016 and 017, B11024-011 thru 013,
B11024-015 thru 019, B11025-001, B11025-011 thru 016, B11025-019 thru 021,
B11026-001 thru 003, B11026-010 thru 012, B11026-015, B11026-017 thru 023,
B11052-003 and 004, B11052-012 and 013, B11052-015 and 016, B11054-013,
B11055-003 and 004, B11055-011 and 012, B11055-017, B11055-019 and 020,
B11061-002, B11061-015 thru 017, B11064-002 thru 004, B11064-013 thru 017,
B11064-020, B11064-022, B11065-001 and 002, B11065-004, B11065-006 and 007,
B11065-009, B11065-012 thru 018, B11079-004, B11079-013 and 014, B11079-016,
B11079-019, B11079-021 thru 024, B11079-029 thru 031, B11080-002, B11080-009
thru 011, B11080-016, B11080-021, B11083-019 thru 022, B11083-024 thru 027,
B11087-003 thru 005, B11087-007 thru 013, B11099-012 and 013, B11099-016
thru 026, B11103-003, B11103-008, B11103-011 thru 015, B11104-002 thru 005,
B11104-009, B11107-002 thru 004, B11107-011, B11107-014 thru 020,
B11107-025, B11115-003 and 004, B11115-012 and 013, B11115-018 thru 021,
B11115-025 and 026, B11120-019, B11120-021, B11127-008 thru 010, B11127-013
and 014, B11129-001, B11129-009 and 010, B11129-013 and 014, B11131-011 thru
013, B11131-015 thru 017, B11148-012, B11148-016 thru 023, B11156-009,
B11156-013 thru 017, B11163-002, B11163-015, B11163-017 thru 021,
B11180-001, B11180-004, B11180-009 thru 012, B11180-014 and 015, B11180-017,
B11181-001, B11181-003, B11181-009, B11181-011 thru 015, B11202-001 thru
004, B11202-014 thru 016, B11202-021 and 022, B11213-001, B11213-003 and
004, B11213-007, B11213-010 thru 014, B11213-022, B11217-010 thru 013,
B11217-015, B11239-003, B11239-006, B11239-015, B11239-023 and 024,
B11239-026, B11239-030, B11244-014, B11244-017, B11244-020, B11244-022,
B11247-001, B11247-016, B11247-018, B11247-021, B11262-016, B11266-014,
B11266-016, B11266-018 and 019, B11266-023, B11281-021, B11281-023,
B11282-015, B11282-019, B11286-013 and 014, B11296-010 thru 013, B11296-015,
B11324-027, B11324-030, B11327-014 and 015, B11349-009, B11350-012,
B11350-017, B11350-019, B11363-012, B11363-015, B11367-018 thru 020,
B11367-030 and 031, B11410-012 and 013, B11432-012, B11432-014, B11468-013
and 014, B7406-001 thru 031, B7406-034 thru 037, B7406-045 thru 047,
B7406-050 thru 061, B7406-065 thru 067, B7406-069 thru 077, B7417-001 thru
013, B7417-015 , B7417-019 thru 023, B7417-037 thru 042, B7417-044 thru 046,
B7417-048, B7417-050, B7417-054 thru 058, B7430-001 thru 014, B7430-018,
B7430-020, B7430-026 and 027, B7430-035 thru 037, B7430-039 thru 079,
B8410-012 thru 037, B8410-039 thru 052, B8411-002 and 003, B8411-007,
B8411-014 and 015, B8411-017 thru 056, B8414-001 thru 008, B8414-015 thru
029, B8421-001, B8421-003, B8421-005 and 006, B8421-009, B8421-024 thru 048,
B8421-051 thru 058, B8422-001 thru 006, B8422-008, B8422-012, B8422-018 thru
028, B8422-030 thru 032, B8422-035 thru 039, B8422-043, B8422-045 thru 047,
B8422-050 and 052, B8422-054, B8424-001 thru 004, B8424-008, B8424-010,
B8424-014 thru 016, B8424-022 thru 032, B8424-034 and 035, B8424-037 thru
044, B8425-010 thru 019, B8425-021 and 022, B8425-025 thru 027, B8684-001
thru 005, B8684-007 and 008, B8684-010, B8684-016 thru 030, B8684-032,
B8684-034 and 035, B8684-037 thru 050, B8685-001 thru 003, B8685-011 thru
042, B8695-002 and 003, B8695-005 thru 013, B8695-023 thru 061, B8697-001,
B8697-006, B8697-014, B8697-017 and 018, B8697-020 and 021, B8697-037 thru
039, B8697-041, B8697-043 thru 058, B8706-001 and 002, B8706-006 thru 009,
B8706-013, B8706-019 thru 023, B8706-025 thru 048, B8707-007 thru 014,
B8707-016 thru 019, B8708-008 thru 025, B8720-001, B8720-003 thru 005,
B8720-009, B8720-012, B8720-021 thru 025, B8720-027 thru 033, B8720-035 and
036, B8720-038 and 039, B8720-040 , B8720-042 thru 062, B8722-002, B8722-010
and 011, B8722-017 thru 025, B8722-027 thru 042, B8723-001, B8723-004 thru
007, B8723-016, B8723-025 and 026, B8723-028 and 029, B8723-031 thru 33,
B8731-013 and 014, B8731-017, B8731-021 and 022, B8731-026 thru 045,
B8732-001, B8732-004 and 005, B8732-005, B8732-016 thru 024, B8732-026 thru
045, B8734-021 thru 023, B8734-027, B8734-029 thru 031, B8734-033, B8734-037
and 038, B8734-041, B8734-043 thru 053, B8734-055 thru 057, B9132-002 thru
005, B9132-010, B9132-014 thru 029, B9228-007 thru 018, B9232-004, B9232-010
and 011, B9232-016 thru 023, B9243-001, B9243-003, B9243-005, B9243-011,
B9243-014, B9243-016, B9243-018 thru 027, B9245-001, B9245-009, B9245-013
and 014, B9245-014, B9245-017, B9245-019 thru 028, B9284-001 thru 005,
B9284-007, B9284-011 thru 020, B9284-023 thru 026, B9284-029 thru 042,
B9285-001 and 002, B9285-004, B9285-012 and 013, B9285-016, B9285-019 thru
027, B9285-029, B9322-002 thru 004, B9322-007, B9322-013 thru 022, B9322-024
thru 026, B9323-001, B9323-006 and 007, B9323-017, B9323-019 thru 030,
B9331-001, B9331-004 thru 007, B9331-017, B9331-020 thru 028, B9331-031 thru
042, B9333-001 thru 003, B9333-005 and 006, B9333-012, B9333-015 thru 020,
B9340-002 and 003, B9340-006 and 007, B9340-010 thru 012, B9340-014 thru
022, B9491-001 thru 003, B9491-006, B9491-011 thru 013, B9491-017 thru 023,
B9509-001, B9509-012, B9509-018 thru 022, B9693-002, B9693-008 thru 015,
B9725-001, B9725-005 and 006, B9725-012 thru 031, B9725-033 thru 037,
B9765-002 and 003, B9765-005 thru 007, B9765-015, B9765-018 thru 022,
B9927-001 thru 004, B9927-007, B9927-009 thru 011, B9927-013 thru 029,
B9927-031 thru 033, C10602-016 thru 021
Repliform
B10084-019 and 020, B10084-022, B10084-024, B10134-016, B10192-013,
B10192-015, B10192-018, B10192-020 thru 023, B10819-027, B11120-008 thru 11,
B7406-044, B7406-048, B7406-064, B7406-078 thru 83, B7417-031 and 32,
B7430-038, B8414-014, B8421-020, B8421-022 and 23, B8422-042, B8424-036,
B8684-015, B8685-005 thru 8, B8697-040, B8697-042, B8706-024, B8723-019,
B8723-024, B8734-042, B9232-014 and 015, B9243-015, B9245-018, B9284-027 and
028, B9285-015, B9285-017 and 018, B9333-007 and 08, B9333-010 and 011,
B9509-015, B9725-007, B9765-008, C10602015
Graft Jacket
B10084-016, B10084-021, B10085-014 thru 016, B10088-023 and 024, B10134-013,
B10838-015, B11021-006, B11052-010, B11065-011, B11079-009, B11087-006,
B11131-008, B11148-009, B11163-016, B11163-008 and 009, B11181-010,
B11266-012, B7406-062, B7417-051 thru 053, B8421-049 and 050, B8422-041,
B8684-036, B8695-019, B8697-032, B8706-014, B8720-016, B8720-019, B8720-020,
B8720-034, B8720-037, B8732-025, B8732-013, B9243-013, B9245-015, B9245-016,
B9284-022, B9331-029 and 030, B9340-009, B9491-014, B9765-013, B9765-016
RECALLING FIRM/MANUFACTURER
LifeCell Corporation, Branchburg, NJ, by telephone and facsimile
transmission beginning September 30, 2005, and by follow-up letter dated
October 12, 2005. Firm initiated recall is ongoing.
REASON
Human Tissues, procured from donors without adequate donor eligibility
determinations, were distributed.
VOLUME OF PRODUCT IN COMMERCE
1,652 allografts from 102 lots
DISTRIBUTION
Nationwide, Australia and Korea

http://www.fda.gov/bbs/topics/enforce/2005/ENF00932.html


TSS



----- Original Message -----
From: "Terry S. Singeltary Sr." <[email protected]>
To: <[email protected]>
Sent: Saturday, December 24, 2005 9:57 AM
Subject: Re: THE LEGAL TRADING AND SELLING OF BODY PARTS AND HUMAN TSEs IN
THE USA


> ##################### Bovine Spongiform Encephalopathy
#####################
>
> Subject: Possible body parts theft ring uncovered (spreading TSEs from
> stolen body parts perfectly legal in Texas after 4 hours)
> Date: December 24, 2005 at 7:36 am PST
>
> Dec. 23, 2005, 11:44PM
> Possible body parts theft ring uncovered
> Skin and bones are alleged to have been sold secretly
>
> By TOM HAYS
> Associated Press
>
> NEW YORK - Michael Bruno's life had been uncomplicated: He was an
immigrant
> who worked hard, spoke his mind and succumbed to kidney cancer two years
ago
> at 75.
>
> "Typical Italian cab driver," recalled his son, Vito. "He had an opinion
> about everything."
>
> It's only after death that his story became ghoulish.
>
> Authorities believe his body and those of hundreds of other people —
> including famed British broadcaster Alistair Cooke — were secretly carved
up
> in the back rooms of several funeral parlors citywide to remove bone, skin
> and tendons, without the required permission from their families.
> Authorities allege the body parts were then sold for a profit.
>
> Worse, health officials fear some of the stolen body parts were diseased,
> and could infect patients who received them in skin grafts, dental
implants
> or other orthopedic procedures — a risk concealed by paperwork doctored
with
> forged signatures and false information.
>
> "It's not just disrespectful to my father," said Vito Bruno, who has sued
> one of the funeral homes. "It's an absolutely hideous crime against other
> people."
>
> In the Cooke case, authorities confirmed this week that investigators
> contacted the late broadcaster's family after finding paperwork indicating
> his bones had been removed and sold by a Fort Lee, N.J., tissue bank,
> Biomedical Tissue Services, before he was cremated. Cooke, best known as
the
> host of PBS's Masterpiece Theatre, died from cancer last year at 95 in
> Manhattan.
>
> Violation of FDA rules
> The family insists it never signed off on the procedure, and that someone
> had falsified documents by changing his cause of death to heart attack,
and
> by lowering his age to 85. Harvesting bones from cancer patients violates
> rules by the Food and Drug Administration.
>
> A state grand jury in Brooklyn has been hearing evidence against at least
a
> half dozen funeral homes in the borough and against Biomedical Tissue
> Services. Authorities allege that they illegally profited by conspiring to
> sell stolen body parts, and say indictments could be handed up early next
> year.
>
> The scandal's reach extends beyond the New York City area. In the fall,
the
> FDA ordered a recall of products produced by tissue processors in Texas,
New
> Jersey, Florida and Georgia, all customers of Biomedical Tissue Services.
>
> Health officials advised physicians that patients who were implanted with
> the tissue should be tested for HIV, hepatitis and other infectious
> diseases. The officials said they believed the health hazards were
minimal,
> and no infections have been reported since the FDA warning.
>
> But past cases have demonstrated dire risks. In 2001, a Minnesota man died
> after a knee surgery from an infection traced to cartilage from an
infected
> donor. A year later, health officials in Oregon announced that several
> patients were infected with hepatitis C after receiving donated organs and
> tissue from a single corpse.
>
> Authorities say the Brooklyn case stems from a deal struck between a
dentist
> who started Biomedical Tissue Services, Michael Mastromarino, 42, of Fort
> Lee, and Joseph Nicelli, 49, an embalmer and funeral parlor operator from
> Staten Island.
>
> Alleged harvesting scheme
> Investigators suspect Nicelli helped secure access to tissue and bones
from
> funeral directors for $500 to $1,000 a body. Mastromarino allegedly would
> remove the body parts, then ship them to processors paying thousands of
> dollars per order.
>
> Attorneys for Nicelli and Mastromarino did not respond to numerous phone
> messages left by the Associated Press, but have previously denied that
their
> clients did anything wrong. A phone number listed for Biomedical Tissue
> Services was disconnected.
>
>
> http://www.chron.com/disp/story.mpl/nation/3545690.html
>
>
> Dec. 23, 2005, 11:05AM
> Authorities Probe Theft of Body Parts
>
> By TOM HAYS Associated Press Writer
> © 2005 The Associated Press
>
> NEW YORK — Authorities are investigating allegations that hundreds of
bodies
> were illegally carved up in funeral homes around New York City and sold
for
> parts without the permission of the families of the deceased.
>
> Corpses _ including that of famed British broadcaster Alistair Cooke _
were
> used to harvest human bone, skin and tendons which were then sold for a
> profit, authorities allege.
>
> Worse, health officials fear some of the stolen body parts were diseased,
> and could infect patients who received them in skin grafts, dental
implants
> or other orthopedic procedures _ a risk concealed by paperwork doctored
with
> forged signatures and false information.
>
> "It's not just disrespectful to my father," said Vito Bruno, who has sued
> one of the funeral homes after his father Michael's corpse was desecrated.
> "It's an absolutely hideous crime against other people."
>
> In the Cooke case, authorities confirmed this week that investigators
> contacted the late broadcaster's family after finding paperwork indicating
> his bones had been removed and sold by a Fort Lee, N.J., tissue bank,
> Biomedical Tissue Services, before he was cremated. Cooke, best known as
the
> host of "Masterpiece Theatre," died from cancer last year at 95 in
> Manhattan.
>
> The family insists it never signed off on the procedure, and that someone
> had falsified documents by changing his cause of death to heart attack,
and
> by lowering his age to 85. Harvesting bones from cancer patients violates
> rules by the Food and Drug Administration.
>
> A daughter, Susan Cooke Kittredge, said the family was "shocked and
> saddened" by the news.
>
> "That people in need would have received his body parts, considering his
age
> and the fact he was ill when he died, is appalling to the family, as is
that
> his remains were violated," she said.
>
> The probe _ first reported by the Daily News in October _ has generated
> other gruesome stories. In one instance, the corpse of a Queens
grandmother
> that investigators exhumed last month had nearly all the bones removed
below
> the waist and replaced with PCV pipes.
>
> A grand jury in Brooklyn has been hearing evidence against at least a half
> dozen funeral homes in the borough and against Biomedical Tissue Services
> that they illegally profited by conspiring to sell stolen body parts.
> Authorities say indictments could be handed up early next year.
>
> The brewing scandal's reach extends far beyond the New York City area.
>
> In the fall, the FDA ordered a recall of products produced by tissue
> processors in New Jersey, Florida, Georgia and Texas, all customers of
> Biomedical Tissue Services. Since the announcement, authorities in Canada
> have determined that about 300 potentially tainted products were imported
> there, and used for dental surgery on at least two patients.
>
> Health officials advised physicians that patients who were implanted with
> the tissue should be tested for HIV, hepatitis and other infectious
> diseases. The officials said they believed the health hazards were
minimal,
> and no infections have been reported since the FDA warning.
>
> But past cases have demonstrated dire risks.
>
> In 2001, a Minnesota man died after a knee surgery from an infection
caused
> by a bacterium traced to cartilage from an infected donor. A year later,
> health officials in Oregon announced that several patients were infected
> with hepatitis C after receiving donated organs and tissue from a single
> corpse.
>
> Authorities say the Brooklyn case stems from a deal struck between a
dentist
> who started Biomedical Tissue Services, Michael Mastromarino, 42, of Fort
> Lee, and Joseph Nicelli, 49, an embalmer and funeral parlor operator from
> Staten Island.
>
> Investigators suspect Nicelli helped secure access to tissue and bones
from
> funeral directors for $500 to $1,000 a body. Mastromarino allegedly would
> remove the body parts, then ship them to processors paying thousands of
> dollars per order.
>
> Attorneys for both Nicelli and Mastromarino did not respond to numerous
> phone messages left by The Associated Press. A phone number listed for
> Biomedical Tissue Services was disconnected.
>
> The Brooklyn case demonstrates the potential pitfalls of allowing funeral
> homes and tissue banks to do business without stricter oversight, said
Annie
> Cheney, author of the upcoming book, "Body Brokers: Inside America's
> Underground Trade in Human Remains."
>
> "The fact that these people were supposedly able to get away with this for
> so long is shocking," she said.
>
>
> http://www.chron.com/disp/story.mpl/ap/nation/3544706.html
>
>
> Dec. 23, 2005, 10:35AM
> Allegations of body part sales investigated
>
> Associated Press
>
> NEW YORK — Authorities are investigating allegations that the body of
> British broadcaster Alistair Cooke — among hundreds of others — was
> illegally carved up in the back room of a funeral home and sold so its
parts
> could be used in transplants.
>
> Officials confirmed this week that investigators found paperwork
indicating
> Cooke's bones had been removed and sold by Biomedical Tissue Services, a
> Fort Lee, N.J., tissue bank, before he was cremated.
>
> Cooke, longtime host of PBS' "Masterpiece Theatre" and known around the
> world for his "Letter From America" shows on the BBC, died from cancer
last
> year at age 95 in New York.
>
> His family said it never agreed to the bone removal and that someone
> falsified documents by changing Cooke's cause of death to heart attack and
> by lowering his age to 85.
>
> A day after his death, Cooke's bones were allegedly sold for about $7,000
to
> two transplant companies. The family was supplied with what they were told
> were his ashes, and scattered them in Central Park.
>
> A daughter, Susan Cooke Kittredge, said the family was "shocked and
> saddened" by the news.
>
> "That people in need would have received his body parts, considering his
age
> and the fact he was ill when he died, is appalling to the family, as is
that
> his remains were violated," she said.
>
> A phone number listed for Biomedical Tissue Services was disconnected.
>
>
> http://www.chron.com/disp/story.mpl/nation/3544620.html
>
>
> TSS
>
>
> ----- Original Message -----
> From: "Terry S. Singeltary Sr."
> To:
> Sent: Tuesday, December 20, 2005 4:25 PM
> Subject: Re: THE LEGAL TRADING AND SELLING OF BODY PARTS AND HUMAN TSEs IN
> THE USA
>
>
> > ##################### Bovine Spongiform Encephalopathy
> #####################
> >
> > Subject: Biomedical Tissue Services (BTS) THE BODY SNATCHERS and mad cow
> > disease i.e. CJD and other dangerous pathogens
> > Date: December 20, 2005 at 2:05 pm PST
> >
> >
> > Greetings BSE-L et al;
> >
> >
> > well, the 'dear unlucky john recipient' letters are in the mail, while
> these
> > company's are laughing all the way to the bank. ...TSS
> >
> >
> > Biomedical Tissue Services (BTS) THE BODY SNATCHERS and mad cow disease
> i.e.
> > CJD and other dangerous pathogens
> >
> >
> >
> > Body snatchers tied to allograft firms?
> > Alleged New York-area ring investigated for selling parts to corpse
tissue
> > harvesters.
> > October 7, 2005: 2:54 PM EDT
> > By Aaron Smith, CNN/Money staff writer
> >
> >
> >
> >
> > NEW YORK (CNN/Money) - A Brooklyn funeral home and a New Jersey company
> that
> > harvests body parts from corpses are being investigated for their
alleged
> > roles in a body snatching ring that sold parts to companies specializing
> in
> > medical grafts, sources close to the investigation said Friday.
> >
> > The Brooklyn district attorney's office declined to comment on the
> > investigation. But sources close to the investigation acknowledged that
it
> > has been going on for about one and a half years, focusing on Michael
> > Mastromarino of Biomedical Tissue Services Ltd. of Fort Lee, N.J., who
> > allegedly harvested body parts illegally from the Daniel George funeral
> home
> > in Brooklyn.
> >
> > The firms that bought the allegedly black-market tissue have not been
> > accused of any wrongdoing. Human tissue is usually obtained from
> non-profit
> > tissue banks. In the U.S., it's illegal to buy and sell human tissue.
> >
> > Wendy Crites-Wacker, spokeswoman for Regeneration Technologies (down
$0.66
> > to $7.28, Research), a company in Alachua, Fla., said her company has
> > severed all ties with Biomedical Tissue Services, their former source
for
> > some of the body parts used to make medical grafts, or allografts.
> >
> > "We had previously terminated the relationship with Biomedical Tissue
> > Services and we are cooperating with the appropriate authorities on this
> > issue," said Crites-Wacker, who declined to say when the termination
took
> > place.
> >
> > Crites-Wacker also said that her company's BioCleanse process, in which
> > bones and tendons are sterilized through a melange of chemicals,
> temperature
> > and pressure, ensures that its products are safe.
> >
> > Two other allograft companies have been identified as customers of
> > Biomedical Tissue Services: LifeCell Corp. (down $2.82 to $17.33,
> Research),
> > of Branchburg, N.J. and Tutogen Medical Inc. (down $0.15 to $4.06,
> Research)
> > of West Paterson, N.J.
> >
> > LifeCell Corp. had issued a Friday statement saying it had voluntarily
> > recalled some human tissue products after questions were raised about
> > Biomedical Tissue Services.
> >
> > "Specifically, the company recalled all lots of product that were
produced
> > using tissue from Biomedical Tissue Services (BTS)," LifeCell said in a
> > release.
> >
> > LifeCell, which markets products made from human tissues that are used
in
> > surgical procedures, said it recalled certain AlloDerm, Repliform and
> > GraftJacket products on Sept. 30.
> >
> > LifeCell's stock price slid about 5 percent this morning, and a Piper
> > Jaffray analyst attributed the slump to a New York Daily News story that
> > first reported on the investigation.
> >
> > "We believe this morning's weakness in LifeCell's shares is related to a
> > news article that alleges LifeCell inadvertently received tissue from an
> > illegal body-snatching ring," said Raj Denhoy of Piper Jaffray, in a
> written
> > report.
> >
> > LifeCell said in the statement all other tissues supplied by Biomedical
> > Tissue Services remain "on hold until the discrepancies in the donor
> > documentation can be resolved."
> >
> > Denhoy said that LifeCell did not appear to do anything illegal and that
> > "LifeCell itself was the victim of fraud," referring to allegations that
> > Biomedical Tissue Services forged death certificates and family consent
> > forms.
> >
> > Denhoy said that LifeCell receives tissue from 30 sources, "so the loss
of
> > one will likely not impact the underlying business," though increased
> > regulatory scrutiny could drive down the stock price.
> >
> > "While LifeCell and the other tissue companies appear to have done
nothing
> > wrong, this event could increase regulatory and media scrutiny of the
> > business," said Denhoy, who rates the company market perform. "We
recently
> > downgraded LifeCell shares on competitive concerns and today's
revelations
> > may pressure the stock further."
> >
> > Eric Franz, the attorney representing funeral home owners Debora Johnson
> and
> > Robert Nelms, said his clients "did not participate in any criminal
> conduct
> > whatsoever."
> >
> > Attempts to reach Mastromarino and his company Biomedical Tissue
Services
> > were unsuccessful. The Daily News reported that Mastromarino declined to
> > comment.
> >
> > Regeneration Technologies produces heart valves, bone and tendon
implants
> > and bone paste, which is used to plug holes. LifeCell specializes in
> > AlloDerm, a "dermal matrix" made from human skin that is used in grafts.
> > Tutogen focuses on bone and dental implants.
> >
> > --from staff and wire reports
> >
> >
> >
> >
> >
http://money.cnn.com/2005/10/07/news/midcaps/corpse/?section=money_latest
> >
> >
> > FDA News
> > FOR IMMEDIATE RELEASE
> > P05-77
> > October 26, 2005
> > Media Inquiries:
> > Julie Zawisza, 301-827-6242
> > Consumer Inquiries:
> > 888-INFO-FDA
> >
> >
> >
> > FDA Provides Information on Investigation into Human Tissue for
> > Transplantation
> > The Food and Drug Administration (FDA) is notifying the public of its
> > investigation of human tissue recovered by Biomedical Tissue Services,
> Ltd.
> > (BTS) of Ft. Lee, NJ, and sent to tissue processors. Some of this tissue
> may
> > have been implanted into patients from early 2004 to September 2005. The
> > tissue was recovered by BTS from human donors who may not have met FDA
> donor
> > eligibility requirements and who may not have been properly screened for
> > certain infectious diseases. At this time, the implicated tissues from
BTS
> > include human bone, skin, and tendons. These products represent only a
> small
> > percentage of the overall U.S. tissue supply.
> >
> > While no adverse reactions related to these tissues have been reported
to
> > FDA at this time, because of the potential lack of proper screening of
the
> > tissue donors, some recipients of the tissues may be at increased risk
of
> > infections that could potentially be transmitted through tissues. FDA
and
> > the Centers for Disease Control and Prevention (CDC) believe the risks
> from
> > these tissues are low because the tissues were routinely processed using
> > methods that help to reduce the risk of infectious disease; however, the
> > actual infectious risk is unknown.
> >
> > FDA's requirements to determine donor eligibility include important
steps
> to
> > ensure that donors do not harbor infections that could be transmitted to
> > recipients. These steps include reviewing the donor's medical history
and
> > other factors, physically assessing the donor, and testing for relevant
> > communicable diseases that may place the donor at an increased risk of
> > infections that could then unintentionally be transmitted to recipients
> > through the tissues.
> >
> > The following tissue processors received tissue from BTS:
> >
> > LifeCell Corporation of Branchburg, NJ
> > Lost Mountain Tissue Bank of Kennesaw, GA
> > Blood and Tissue Center of Central Texas in Austin, TX
> > Tutogen Medical, Inc., of Alachua, FL
> > Regeneration Technologies, Inc., of Alachua, FL
> > These firms already have voluntarily recalled all unused tissue
remaining
> in
> > inventory and are working cooperatively with FDA to ensure that the
> > implanting physicians whose patients may have received the products are
> > properly notified. Physicians who implanted tissue from BTS should have
> been
> > contacted at this time by the receiving health care facility.
> >
> > FDA and CDC recommend that implanting physicians inform their patients
> that
> > they may have received tissue from a donor for whom an adequate donor
> > eligibility determination was not performed. While the overall
infectious
> > risk is likely low, FDA and CDC recommend that physicians offer to
provide
> > patients access to appropriate infectious disease testing. The relevant
> > communicable diseases for which a tissue donor is required to be tested
> are
> > HIV-1 and 2 (the viruses that cause AIDS), hepatitis B virus, hepatitis
C
> > virus, and syphilis. Physicians who still have concerns or questions
about
> > the source of the tissue should contact the health care facility where
the
> > procedure was performed. FDA will continue its investigation into this
> > matter and will issue further public health updates, as needed.
> >
> > Patients and physicians should report any infectious disease possibly
> > related to a tissue transplant to the processing firms, who then should
> > notify FDA. Patients and physicians who wish to notify FDA directly of
> such
> > infectious disease should report via FDA's MedWatch reporting program at
> > http://www.fda.gov/medwatch.
> >
> >
> > http://www.fda.gov/bbs/topics/NEWS/2005/NEW01249.html
> >
> >
> >
> > Recall of Human Tissue
> >
> >
> > DATE RECALL INITIATED:
> >
> > October 13, 2005
> >
> > PRODUCT:
> >
> > Human Tissue for Transplantation
> >
> > MANUFACTURER:
> >
> > Biomedical Tissue Services, Ltd
> > Fort Lee, New Jersey
> >
> > REASON:
> >
> > Biomedical Tissue Services (BTS) was recently made aware that there is
the
> > possibility that tissue has been procured from donors without proper
> > medical/social histories. BTS is performing a voluntary recall of any
> unused
> > tissue from its consignees.
> >
> >
> > The information in this listing reflects CBER's best efforts to
> communicate
> > information that has been reported to FDA. Its accuracy and
> > comprehensiveness cannot be guaranteed.
> >
> >
> >
> >
> > Updated October 18, 2005
> >
> >
> > http://www.fda.gov/cber/recalls/btstis101305.htm
> >
> >
> >
> >
> > Tutogen Medical Tissue Recall
> >
> > Frequently Asked Questions and Answers
> >
> > Q: What prompted this recall?
> >
> > A: Tutogen was unable to verify donor consent for certain tissue
provided
> by
> > one of its recovery agency suppliers (BioMedical Tissue Services of Fort
> > Lee, NJ). Tutogen, along with several other tissue processing companies,
> > received allograft material from BioMedical Tissue Services. One of
these
> > other processing companies notified Tutogen that they were having
> difficulty
> > in reaching persons taking the consent information or next of kin for
> > BioMedical tissue donors. Upon receiving this notification, Tutogen
> > immediately initiated a review and investigation of all donor consents
> > received from BioMedical Tissue Services. Tutogen also experienced
> problems
> > in contacting consent takers, witnesses and next of kin shown on the
> > documentation provided by BioMedical Tissue Services. We further
attempted
> > to contact Dr. Michael Mastromarino, CEO and Executive Director of
> > BioMedical Tissue Services, to assist in this matter, but without
success.
> > Although Tutogen does not believe that there are any safety concerns
> related
> > to this tissue, the company elected to initiate a voluntary recall of
> > products incorporating the BioMedical tissues, on ethical grounds.
> >
> > Q: What tissue products are being recalled?
> >
> > A: Specific serial/lot numbers of Tutogen's Puros® Allograft Cancellous
> > Particles (marketed by Zimmer Dental) and a small quantity of Tutoplast®
> > Fascia Lata (marketed by Mentor Corporation and Innovative Opthalmic
> > Products, Inc.) are involved in this recall.
> >
> > Q: How much allograft tissue did BioMedical Tissue Services provide to
> > Tutogen?
> >
> > A: The quantity of tissue received from BioMedical represents a small
> > fraction (about 2%) of all tissue processed by Tutogen.
> >
> > Q: What did Tutogen do to notify customers of the recall?
> >
> > A: Upon completion of its donor documentation investigation, Tutogen
> > notified the FDA of our intent to initiate a voluntary recall. We
> > immediately identified all BioMedical tissue, from raw material stock
> > through finished goods and field distribution, and quarantined all
> material
> > within our control. Customer shipment information was assembled and a
> recall
> > letter was prepared and approved by the FDA. Initially, Tutogen alerted
> all
> > customers of record via telephone, describing the reason for the recall,
> > providing serial numbers of product shipped to them and indicating the
> > process for the return and replacement of affected product.
> >
> > Simultaneously, copies of the recall letter and distribution information
> for
> > the affected product was sent to each customer by facsimile. This same
> > information was then provided to customer accounts by certified mail. At
> the
> > request of the FDA, Tutogen sent a recall follow-up letter to affected
> > customers, including FDA mandated language regarding patient
notification
> > and access to disease testing.
> >
> > An additional letter was prepared and mailed to those customers that had
> not
> > received any of the products manufactured using BioMedical tissue and
were
> > not affected by the voluntary recall. In the interim, the company
prepared
> > and issued a press release concerning this recall and participated in
> > numerous conference calls, throughout the U.S. and Canada, with surgeon
> > groups, industry organizations (such as the American Association of
Tissue
> > Banks) and professional associations (such as the American Association
of
> > Oral and Maxillofacial Surgeons and the American Academy of
> Periodontology).
> >
> > These prior communications were supplemented by a scientific
dissertation
> > mail-out that described the Tutogen Tutoplast® process, which
subsequently
> > led to the preparation of a technical monograph detailing this process
and
> > its qualification history. The monograph may be accessed on this website
> by
> > selecting the link entitled, "The Tutoplast® Process: A Review of
> Efficacy".
> >
> > Q: How can I tell whether I received any of the affected product?
> >
> > A: All customers of record, that received products manufactured
utilizing
> > tissue provided by BioMedical, were notified and should have received an
> > individualized list of all product serial numbers shipped to them.
> Affected
> > product may also be quickly identified by visually checking the
> > alpha-numeric designator beneath the product barcode label (see samples,
> > shown below).
> >
> > The affected product alpha-numeric code begins with the letters "BM" or
> > "BT".
> >
> > Q: How should I go about returning affected product that may remain in
my
> > inventory stock?
> >
> > A: Once any affected product has been identified, place it in a shipping
> > container and mark the outside of the container with "BMRECALL". Address
> the
> > package to:
> >
> > Tutogen Medical
> >
> > 13709 Progress Boulevard
> >
> > South Wing
> >
> > Alachua, FL 32615
> >
> > Biomedical Tissue Services
> >
> > Biotissue Recovery Services
> >
> > Call UPS at (800) PICK UPS and request a package pick-up. Forward the
> > package to Tutogen, via UPS ground, using account number Y6X706. This
> > shipping account number is reserved for the return of recalled items and
> is
> > for one-way service to Tutogen, from U.S. accounts. Only product
affected
> by
> > this recall will be accepted for return.
> >
> > Canadian customers should contact Zimmer Dental Corporation Customer
> Service
> > at (800) 265-0968 or (905) 567-2073 for return instructions.
> >
> > Q: What is the risk to patients that have already received recalled
> > implants?
> >
> > A: The FDA and CDC have indicated that they believe the overall risk of
> > disease transmission by these products is low, but unknown. Because
> Tutogen'
> > s Tutoplast® tissue preservation and sterilization process is extremely
> > rigorous and has passed significant challenge testing, we believe that
all
> > tissue distributed by Tutogen, including that from BioMedical Tissue
> > Services, is safe and effective for its intended use. In addition,
> > comprehensive physical examination and serology testing is routinely
> > performed on all donors processed by Tutogen.
> >
> > Q: What types of evaluations are performed on donors processed by
Tutogen
> > Medical?
> >
> > A: Consent for donation, along with a detailed medical/social history,
is
> > obtained from each donor or their next of kin by hospital, medical
> examiner,
> > funeral home or recovery agency personnel. The recovery team identifies
> the
> > donor and conducts a detailed physical evaluation of the body. This
> > examination incorporates an extensive assessment checklist for
> > characteristics that would disqualify a donor from further consideration
> and
> > addresses tissue appearance and condition during the retrieval process.
> The
> > recovery team also collects a donor blood sample and forwards it to a
> > third-party CLIA certified laboratory for disease testing, using FDA
> > approved test methodology. The serology test results, along with the
> > previously mentioned donor documentation, is examined by Tutogen's
Quality
> > Assurance Department and a staff Medical Director (a licensed
physician).
> > Only after these thorough reviews are completed and release is granted
by
> > the Medical Director, is donor tissue allowed to enter the Tutoplast®
> > process.
> >
> > Q: What testing is done on the donor serology sample?
> >
> > A: Tutogen requires that the following serology testing be performed and
> > found to be "negative" or "non-reactive", prior to accepting any donor
> > tissue for processing:
> >
> > Hepatitis B surface antigen (HBsAg)
> >
> > Hepatitis B core antibody (HBcAb – IgG +IgM)
> >
> > Hepatitis C Virus antibody (HCV Ab)
> >
> > Hepatitis B and C Nucleic Acid Testing (HBV and HCV NAT)
> >
> > Human Immunodeficiency Virus I and II antibodies (HIV I and II Ab)
> >
> > HIV I – p24
> >
> > Human T-Lymphotropic Virus I and II (HTLV I and II Ab)
> >
> > Syphilis – Rapid Plasma Reagin (RPR/STS)
> >
> > Q: Who will pay for the cost of disease testing for my patients?
> >
> > A: Although Tutogen does not feel that the products manufactured using
> > BioMedical tissue pose a safety concern, out of respect for your
patients'
> > welfare and as a service to you, Tutogen has elected to bear the cost of
> the
> > appropriate infectious disease testing.
> >
> > Q: What process has Tutogen put in place to accomplish the disease
> testing"?
> >
> > A: We have made arrangements with ViroMed Laboratories (division of
> > LabCorp), a respected, CLIA and FDA certified organization, to conduct
> this
> > testing. Should you choose to inform those patients who received the
> > affected implants, we suggest that you offer them the opportunity to be
> > tested for the specified infectious diseases. Additionally, we recommend
> > that you maintain a record of notification for each patient, which would
> > indicate their acceptance or rejection of the testing offered and be
> > signed/dated by that individual. For those patients that elect to
undergo
> > testing, both U.S. and Canadian customers should follow the process
> > delineated, below.
> >
> >
> > 1. Provide Tutogen Medical with the name and mailing address of the
> patient.
> > Only patients that received implants utilizing tissue provided by
> BioMedical
> > Tissue Services are eligible for this pre-paid testing. This information
> > will be verified in our Tissue Utilization Record (TUR) database, or you
> may
> > provide documentation confirming the patient's implant, if no TUR was
> > previously forwarded to Tutogen.
> >
> >
> > 2. Let the patient know that a test kit will be sent to him or her by
> > ViroMed Laboratories within the next few days and will include
> instructions
> > on how to proceed.
> >
> >
> > 3. Instruct the patient to set up an appointment with and take the test
> kit
> > to their Primary Care physician. Alternatively, the patient may elect to
> > visit a LabCorp service center as indicated in item # 7, below.
> >
> >
> > 4. Following the instructions provided with the kit, the Primary Care
> > physician or professional healthcare office staff member should obtain a
> > blood sample from the patient and forward it to ViroMed Laboratories in
> the
> > postage-paid mailer that will be included in the kit.
> >
> >
> > 5. ViroMed Laboratories will perform the appropriate disease testing and
> > forward the results to the patient's Primary Care physician. If a
> > confirmatory test is necessary, ViroMed Laboratories will automatically
> > perform this additional testing and include those results in the final
> test
> > report.
> >
> >
> > 6. Upon receipt of the ViroMed data, the Primary Care physician should
> > contact the patient and discuss the final results of the testing with
him
> or
> > her.
> >
> >
> > 7. In the event that your patient does not have a Primary Care
physician,
> he
> > or she may go to a "walk-in" clinic to have a blood sample taken or to
be
> > referred to a LabCorp service
> >
> >
> > center near them and have this blood sample drawn and forwarded to
ViroMed
> > Laboratories for testing. The attending physician may call ViroMed
Client
> > Services, at (800) 582-0077, to arrange for a test kit or to obtain
> > instructions for handling the sample. These patients must have their
> > eligibility verified by Tutogen. LabCorp or ViroMed will provide all
> > associated test kit supplies. A list of service center locations is
> > available on the LabCorp website (www.labcorp.com ) under the "Patient
> > Service Center Locator" link.
> >
> > If you have a patient that has already presented for infectious disease
> > testing, a reimbursement request for costs not covered by the individual
's
> > insurance carrier can be made by forwarding the invoice, showing the net
> > responsibility of the patient, or a receipt, marked "Paid" to:
> >
> > Tutogen Medical, Inc.
> >
> > Accounts Payable
> >
> > 13709 Progress Blvd., Box 19
> >
> > Alachua, FL 32615
> >
> > The invoice should clearly show the name and address of the facility
> > performing the disease testing and be annotated with the name of the
> patient
> > 's dentist/oral surgeon and practice name, as well as the identifier,
> > "BMRECALL".
> >
> > Q: What testing will be performed on each patient's blood sample?
> >
> > A: The recommended testing is for HIV I and II, Hepatitis B virus,
> Hepatitis
> > C virus and syphilis. All test results will remain confidential, between
> > patient and doctor.
> >
> > Q: Is Tutogen still receiving tissue from BioMedical Tissue Services?
> >
> > A: No. Upon initiating the voluntary recall, Tutogen suspended the
> > acceptance of any tissues from BioMedical Tissue Services and has
> officially
> > terminated its relationship with them.
> >
> > Q: How can a situation such as this be prevented in the future?
> >
> > A: At this point, there is no simple answer to this question. Tutogen
> > adhered to all of its standard screening, inspection and processing
> > procedures and there was no deviation or departure from its quality
> > assurance systems. All processing companies rely on the FDA registered
and
> > state licensed recovery agencies to comply with established regulations
> and
> > industry guidelines. Tutogen is currently evaluating a number of
potential
> > additional safeguards, but no mechanisms have been identified that would
> > provide a foolproof solution. In addition, we are working very closely
> with
> > the Food and Drug Administration and American Association of Tissue
Banks
> to
> > devise workable options that might preclude recurrence.
> >
> >
> > http://www.tutogen.com/recallQandA.pdf
> >
> >
> > Recall of Human Tissue Products
> >
> >
> > DATE RECALL INITIATED:
> >
> > October 14, 2005
> >
> > PRODUCT:
> >
> > Human Tissue For Transplantation
> >
> > MANUFACTURER:
> >
> > Regeneration Technologies, Inc
> > Alachua, Florida
> >
> > REASON:
> >
> > Regeneration Technologies, Inc. (RTI) is conducting a voluntary recall
of
> > all tissue received from BioMedical Tissue Services (BTS; Ft. Lee, New
> > Jersey) as a result of information regarding the accuracy of donor
> screening
> > documentation. RTI informed its consignees that a lack of assurance of
> donor
> > identity as well as the risk of infectious diseases also exists.
> Consignees
> > are asked to contact the manufacturer to arrange for product return.
> >
> >
> > The information in this listing reflects CBER's best efforts to
> communicate
> > information that has been reported to FDA. Its accuracy and
> > comprehensiveness cannot be guaranteed.
> >
> >
> >
> >
> > Updated October 18, 2005
> >
> >
> >
> >
> > http://www.fda.gov/cber/recalls/rtitis101405.htm
> >
> >
> > FDA News
> > FOR IMMEDIATE RELEASE
> > P05-77
> > October 26, 2005
> > Media Inquiries:
> > Julie Zawisza, 301-827-6242
> > Consumer Inquiries:
> > 888-INFO-FDA
> >
> >
> >
> > FDA Provides Information on Investigation into Human Tissue for
> > Transplantation
> > The Food and Drug Administration (FDA) is notifying the public of its
> > investigation of human tissue recovered by Biomedical Tissue Services,
> Ltd.
> > (BTS) of Ft. Lee, NJ, and sent to tissue processors. Some of this tissue
> may
> > have been implanted into patients from early 2004 to September 2005. The
> > tissue was recovered by BTS from human donors who may not have met FDA
> donor
> > eligibility requirements and who may not have been properly screened for
> > certain infectious diseases. At this time, the implicated tissues from
BTS
> > include human bone, skin, and tendons. These products represent only a
> small
> > percentage of the overall U.S. tissue supply.
> >
> > While no adverse reactions related to these tissues have been reported
to
> > FDA at this time, because of the potential lack of proper screening of
the
> > tissue donors, some recipients of the tissues may be at increased risk
of
> > infections that could potentially be transmitted through tissues. FDA
and
> > the Centers for Disease Control and Prevention (CDC) believe the risks
> from
> > these tissues are low because the tissues were routinely processed using
> > methods that help to reduce the risk of infectious disease; however, the
> > actual infectious risk is unknown.
> >
> > FDA's requirements to determine donor eligibility include important
steps
> to
> > ensure that donors do not harbor infections that could be transmitted to
> > recipients. These steps include reviewing the donor's medical history
and
> > other factors, physically assessing the donor, and testing for relevant
> > communicable diseases that may place the donor at an increased risk of
> > infections that could then unintentionally be transmitted to recipients
> > through the tissues.
> >
> > The following tissue processors received tissue from BTS:
> >
> > LifeCell Corporation of Branchburg, NJ
> > Lost Mountain Tissue Bank of Kennesaw, GA
> > Blood and Tissue Center of Central Texas in Austin, TX
> > Tutogen Medical, Inc., of Alachua, FL
> > Regeneration Technologies, Inc., of Alachua, FL
> > These firms already have voluntarily recalled all unused tissue
remaining
> in
> > inventory and are working cooperatively with FDA to ensure that the
> > implanting physicians whose patients may have received the products are
> > properly notified. Physicians who implanted tissue from BTS should have
> been
> > contacted at this time by the receiving health care facility.
> >
> > FDA and CDC recommend that implanting physicians inform their patients
> that
> > they may have received tissue from a donor for whom an adequate donor
> > eligibility determination was not performed. While the overall
infectious
> > risk is likely low, FDA and CDC recommend that physicians offer to
provide
> > patients access to appropriate infectious disease testing. The relevant
> > communicable diseases for which a tissue donor is required to be tested
> are
> > HIV-1 and 2 (the viruses that cause AIDS), hepatitis B virus, hepatitis
C
> > virus, and syphilis. Physicians who still have concerns or questions
about
> > the source of the tissue should contact the health care facility where
the
> > procedure was performed. FDA will continue its investigation into this
> > matter and will issue further public health updates, as needed.
> >
> > Patients and physicians should report any infectious disease possibly
> > related to a tissue transplant to the processing firms, who then should
> > notify FDA. Patients and physicians who wish to notify FDA directly of
> such
> > infectious disease should report via FDA's MedWatch reporting program at
> > http://www.fda.gov/medwatch.
> >
> > Additional information is available on FDA's web site at
> > http://www.fda.gov/cber/recalls.htm and by calling 1-800-835-4709.
> >
> > ####
> >
> >
> > http://www.fda.gov/bbs/topics/NEWS/2005/NEW01249.html
> >
> >
> > Recall of Human Tissue Products
> >
> >
> > DATE RECALL INITIATED:
> >
> > October 11, 2005
> >
> > PRODUCT:
> >
> > Human Tissue for Transplantation
> >
> > MANUFACTURER:
> >
> > The Blood and Tissue Center of Central Texas
> > Austin, Texas
> >
> > REASON:
> >
> > Central Texas Regional Blood and Tissue Center is voluntarily recalling
> > tissue products as the firm is unable to confirm information provided by
> > BioMedical Tissue Services (BTS; Ft. Lee, New Jersey). Consignees are
> asked
> > to contact the manufacturer to arrange for product return.
> >
> >
> > The information in this listing reflects CBER's best efforts to
> communicate
> > information that has been reported to FDA. Its accuracy and
> > comprehensiveness cannot be guaranteed.
> >
> >
> >
> >
> > Updated October 18, 2005
> >
> >
> >
> >
> > http://www.fda.gov/cber/recalls/blotis101105.htm
> >
> >
> > Recall of Human Tissue Products
> >
> >
> > DATE RECALL INITIATED:
> >
> > October 12, 2005
> >
> > PRODUCT:
> >
> > Human Tissue for Transplantation
> >
> > MANUFACTURER:
> >
> > Tutogen Medical, Inc.
> > Alachua, Florida
> >
> > REASON:
> >
> > Tutogen Medical is conducting a voluntary recall of all materials that
> were
> > manufactured utilizing BioMedical Tissue Services (BTS; Ft. Lee, New
> Jersey)
> > donor tissue. This action is being taken because Tutogen is unable to
> > satisfactorily confirm that donor eligibility had been properly obtained
> by
> > BTS. Tutogen informed its consignees that there is a lack of assurance
> that
> > appropriate donor identification, donor screening, and medical history
> data
> > collection was performed and, therefore, a risk of infectious disease
> > exists. Consignees are asked to contact the manufacturer to arrange for
> > product return.
> >
> >
> > The information in this listing reflects CBER's best efforts to
> communicate
> > information that has been reported to FDA. Its accuracy and
> > comprehensiveness cannot be guaranteed.
> >
> >
> >
> >
> > Updated October 18, 2005
> >
> >
> >
> >
> > http://www.fda.gov/cber/recalls/tutotis101205.htm
> >
> >
> > Withdrawal of Human Tissue Products
> >
> >
> > DATE WITHDRAWAL INITIATED:
> >
> > October 10, 2005
> >
> > PRODUCT:
> >
> > Human Tissue for Transplantation
> >
> > MANUFACTURER:
> >
> > Lost Mountain Tissue Bank
> > Kennesaw, Georgia
> >
> > REASON:
> >
> > Lost Mountain Tissue Bank, Inc. (LMTB) has initiated consignee
> notifications
> > for all tissue products processed and/or distributed from donors
procured
> in
> > the New York area by Biomedical Tissue Services (BTS; Ft. Lee, New
> Jersey).
> > LMTB was informed of some discrepant and possibly fraudulent information
> in
> > donor documentation. LMTB is notifying all relevant hospitals and
medical
> > professionals of the market withdrawal of all tissue products beginning
> with
> > the letters "GL" or "T" in the tissue identification number (ID#).
> >
> >
> > The information in this listing reflects CBER's best efforts to
> communicate
> > information that has been reported to FDA. Its accuracy and
> > comprehensiveness cannot be guaranteed.
> >
> >
> >
> >
> > U

 

[flounder]

> > DATE WITHDRAWAL INITIATED:
> >
> > October 10, 2005
> >
> > PRODUCT:
> >
> > Human Tissue for Transplantation
> >
> > MANUFACTURER:
> >
> > Lost Mountain Tissue Bank
> > Kennesaw, Georgia
> >
> > REASON:
> >
> > Lost Mountain Tissue Bank, Inc. (LMTB) has initiated consignee
> notifications
> > for all tissue products processed and/or distributed from donors
procured
> in
> > the New York area by Biomedical Tissue Services (BTS; Ft. Lee, New
> Jersey).
> > LMTB was informed of some discrepant and possibly fraudulent information
> in
> > donor documentation. LMTB is notifying all relevant hospitals and
medical
> > professionals of the market withdrawal of all tissue products beginning
> with
> > the letters "GL" or "T" in the tissue identification number (ID#).
> >
> >
> > The information in this listing reflects CBER's best efforts to
> communicate
> > information that has been reported to FDA. Its accuracy and
> > comprehensiveness cannot be guaranteed.
> >
> >
> >
> >
> > Updated October 18, 2005
> >
> >
> >
> >
> > http://www.fda.gov/cber/recalls.htm
> >
> >
> > DATE RECALL INITIATED:
> >
> > September 30, 2005
> >
> > PRODUCT:
> >
> > AlloDerm, Repliform, and GraftJacket
> >
> > MANUFACTURER:
> >
> > LifeCell Corporation
> > Branchburg, New Jersey
> >
> > REASON:
> >
> > LifeCell Corporation initiated a voluntary recall of certain AlloDerm,
> > Repliform, and GraftJacket product from the marketplace on September 30,
> > 2005. The recall was prompted when internal quality processes raised
> > questions about the donor documentation received from one tissue
recovery
> > organization. Specifically, the company recalled all lots of product
that
> > were produced using tissue from Biomedical Tissue Services (BTS). Life
> Cell
> > promptly notified the FDA and all relevant hospitals and medical
> > professionals. All other BTS inventory remains on hold until the
> > discrepancies in the donor documentation can be resolved. LifeCell works
> > with more than 40 other tissue recovery organizations that are not
> affected
> > by this recall.
> >
> >
> > The information in this listing reflects CBER's best efforts to
> communicate
> > information that has been reported to FDA. Its accuracy and
> > comprehensiveness cannot be guaranteed.
> >
> >
> >
> > Updated October 12, 2005
> >
> >
> >
> >
> > http://www.fda.gov/cber/recalls/tislife093005.htm
> >
> >
> > Compliance Program
> > Inspection of Human Cells, Tissues, and Cellular and Tissue-Based
Products
> > (HCT/Ps)
> > 7341.002
> >
> >
> > http://www.fda.gov/cber/cpg/7341002tis.htm
> >
> >
> >
> >
> > TSS
> >
> >
> >
> > ----- Original Message -----
> > From: "Terry S. Singeltary Sr."
> > To:
> > Sent: Thursday, October 27, 2005 9:55 AM
> > Subject: THE LEGAL TRADING AND SELLING OF BODY PARTS AND HUMAN TSEs IN
THE
> > USA
> >
> >
> > ##################### Bovine Spongiform Encephalopathy
> #####################
> >
> > From: TSS ()
> > Subject: THE LEGAL TRADING AND SELLING OF BODY PARTS AND HUMAN TSEs IN
THE
> > USA
> > Date: October 27, 2005 at 8:40 am PST
> >
> > WASHINGTON
> > FDA investigating human tissue sales
> > WASHINGTON - The Food and Drug Administration said Wednesday that it is
> > investigating a New Jersey-based company that sold human tissue to
> > processors for eventual implantation into people, because it may not
have
> > been properly screened for infections. The New York Daily News reported
> > earlier this month that the district attorney's office in Brooklyn,
N.Y.,
> is
> > investigating the company, Biomedical Tissue Services of Fort Lee, N.J.,
> on
> > allegations that the company illegally bought body parts from funeral
> homes
> > to sell to tissue processors. An FDA spokeswoman would not comment on
> those
> > allegations. The tissues include human bones, skin and tendons and
> > constitute only a small portion of the U.S. tissue supply, the FDA said.
> > They were implanted between early 2004 and September 2005. The Blood and
> > Tissue Center of Central Texas in Austin received some.
> >
> > http://www.chron.com/cs/CDA/ssistory.mpl/nation/3419112
> >
> >
> > FOR IMMEDIATE RELEASE
> > P05-77
> > October 26, 2005
> > Media Inquiries:
> > Julie Zawisza, 301-827-6242
> > Consumer Inquiries:
> > 888-INFO-FDA
> >
> >
> > FDA Provides Information on Investigation into Human Tissue for
> > Transplantation
> > The Food and Drug Administration (FDA) is notifying the public of its
> > investigation of human tissue recovered by Biomedical Tissue Services,
> Ltd.
> > (BTS) of Ft. Lee, NJ, and sent to tissue processors. Some of this tissue
> may
> > have been implanted into patients from early 2004 to September 2005. The
> > tissue was recovered by BTS from human donors who may not have met FDA
> donor
> > eligibility requirements and who may not have been properly screened for
> > certain infectious diseases. At this time, the implicated tissues from
BTS
> > include human bone, skin, and tendons. These products represent only a
> small
> > percentage of the overall U.S. tissue supply.
> >
> > While no adverse reactions related to these tissues have been reported
to
> > FDA at this time, because of the potential lack of proper screening of
the
> > tissue donors, some recipients of the tissues may be at increased risk
of
> > infections that could potentially be transmitted through tissues. FDA
and
> > the Centers for Disease Control and Prevention (CDC) believe the risks
> from
> > these tissues are low because the tissues were routinely processed using
> > methods that help to reduce the risk of infectious disease; however, the
> > actual infectious risk is unknown.
> >
> > FDA's requirements to determine donor eligibility include important
steps
> to
> > ensure that donors do not harbor infections that could be transmitted to
> > recipients. These steps include reviewing the donor's medical history
and
> > other factors, physically assessing the donor, and testing for relevant
> > communicable diseases that may place the donor at an increased risk of
> > infections that could then unintentionally be transmitted to recipients
> > through the tissues.
> >
> > The following tissue processors received tissue from BTS:
> >
> > LifeCell Corporation of Branchburg, NJ
> > Lost Mountain Tissue Bank of Kennesaw, GA
> > Blood and Tissue Center of Central Texas in Austin, TX
> > Tutogen Medical, Inc., of Alachua, FL
> > Regeneration Technologies, Inc., of Alachua, FL
> > These firms already have voluntarily recalled all unused tissue
remaining
> in
> > inventory and are working cooperatively with FDA to ensure that the
> > implanting physicians whose patients may have received the products are
> > properly notified. Physicians who implanted tissue from BTS should have
> been
> > contacted at this time by the receiving health care facility.
> >
> > FDA and CDC recommend that implanting physicians inform their patients
> that
> > they may have received tissue from a donor for whom an adequate donor
> > eligibility determination was not performed. While the overall
infectious
> > risk is likely low, FDA and CDC recommend that physicians offer to
provide
> > patients access to appropriate infectious disease testing. The relevant
> > communicable diseases for which a tissue donor is required to be tested
> are
> > HIV-1 and 2 (the viruses that cause AIDS), hepatitis B virus, hepatitis
C
> > virus, and syphilis. Physicians who still have concerns or questions
about
> > the source of the tissue should contact the health care facility where
the
> > procedure was performed. FDA will continue its investigation into this
> > matter and will issue further public health updates, as needed.
> >
> > Patients and physicians should report any infectious disease possibly
> > related to a tissue transplant to the processing firms, who then should
> > notify FDA. Patients and physicians who wish to notify FDA directly of
> such
> > infectious disease should report via FDA's MedWatch reporting program at
> > http://www.fda.gov/medwatch.
> >
> > Additional information is available on FDA's web site at
> > http://www.fda.gov/cber/recalls.htm and by calling 1-800-835-4709.
> >
> > ####
> >
> >
> > http://www.fda.gov/bbs/topics/NEWS/2005/NEW01249.html
> >
> >
> > a bit of history;
> >
> >
> > The Eyes have it/CJD * and they could be stealing them from YOUR loved
> > one, hence the spread of CJD (aka MADCOW DISEASE) will spread...
> >
> >
> > ############ Creutzfeldt-Jakob Disease
> > #############
> >
> > Greetings list members, I was impressed that someone is listening,
> > considering the timing of when I broke the story in Nov. and this was
> > posted in Dec., what a coincidence. Thanks for listening. I find it
> > rather frightening of the fact sporadic CJD as well as vCJD can
> >
> > transmit infectivity this way. Makes me wonder about blood?
> > Kind Regards, Terry S. Singeltary Sr., Bacliff, Texas USA
> >
> > Vol. 282 No. 23, December 15, 1999
> > Preventing Prion Transmission in Corneal Transplants
> >
> >
> > http://www.vegsource.com/talk/madcow/messages/7242.html
> >
> >
> > 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://mad-cow.org/~tom/dec99_news.html#bbb
> >
> >
> > VOL. 282 No. 23, December 15, 1999
> >
> > Preventing Prion Transmission in Corneal Transplants
> >
> > To the Editor: We agree with the Council on Scientific Affairs'
> > recommendation that "physicians become knowledgeable about BSE [bovine
> > spongiform encephalopathy] so they can appropriately advise their
patients
> > about routes and rates of BSE transmission."1 Unfortunately, there is
only
> > passing mention of prion transmission by corneal transplantation, which
is
> > performed on 40,000 to 50,000 patients each year in the United States.2
In
> > addition to the 1974 US case,3 2 additional cases of probable and
possible
> > transmission, respectively, have been reported in Germany and Japan,3
but
> > the major new concern relative to prion transmission via corneas
occurred
> > recently in Great Britain. In February 1997, the corneal transplant and
> > sclera from a 53-year-old woman who had died of presumed metastatic lung
> > cancer were transplanted to 3 recipients.4 In November 1997, the donor's
> > brain revealed sporadic Creutzfeldt-Jakob disease (CJD), confirmed by
the
> > United Kingdom CJD Surveillance Unit.4 . . . [Full Text of this Article]
> >
> >
> >
>
http://jama.ama-assn.org/cgi/content/extract/282/23/2211?maxtoshow=&HITS=10&
> >
>
hits=10&RESULTFORMAT=&fulltext=CJD+EYE&searchid=1130425573446_2695&stored_se
> > arch=&FIRSTINDEX=0&journalcode=jama
> >
> >
> > http://www.vegsource.com/talk/madcow/messages/7643.html
> >
> >
> > http://www.vegsource.com/talk/madcow/messages/7708.html
> >
> >
> > VVOL
> >
> > http://mad-cow.org/~tom/dec99_news.html#bbb
> >
> >
> > 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
> >
> >
> > re-use contact lenses
> >
> >
> > http://www.vegsource.com/talk/madcow/messages/7691.html
> >
> >
> > TSS
> >
> >
> > Link: Reported by Terry S. Singeltary Sr. son of CJD victim 28 Nov 99
THE
> > EYES HAVE IT, CJD...
> >
> >
> > #################### https://lists.aegee.org/bse-l.html
> ####################
> >



From: TSS ()
Subject: The beauty products from the skin of executed Chinese prisoners AND CJD
Date: September 13, 2005 at 8:10 am PST

Special report

--------------------------------------------------------------------------------
The beauty products from the skin of executed Chinese prisoners

· Cosmetics firm targets UK market ·
Lack of regulation puts users at risk

Ian Cobain and Adam Luck
Tuesday September 13, 2005
The Guardian


A Chinese cosmetics company is using skin harvested from the corpses of executed convicts to develop beauty products for sale in Europe, an investigation by the Guardian has discovered.
Agents for the firm have told would-be customers it is developing collagen for lip and wrinkle treatments from skin taken from prisoners after they have been shot. The agents say some of the company's products have been exported to the UK, and that the use of skin from condemned convicts is "traditional" and nothing to "make such a big fuss about".


With European regulations to control cosmetic treatments such as collagen not expected for several years, doctors and politicians say the discovery highlights the dangers faced by the increasing number of Britons seeking to improve their looks. Apart from the ethical concerns, there is also the potential risk of infection.
MPs on the Commons select health committee are to examine the regulatory system and may launch an investigation and question ministers about the need for immediate new controls. "I am sure that the committee will want to look at this," said Kevin Barron, its Labour chairman. "This is something everyone in society will be very concerned about."

Plastic surgeons are also concerned about the delay in introducing regulations to control the cosmetic treatments industry. Norman Waterhouse, a former president of the British Association of Aesthetic Plastic Surgeons, said: "I am surprised that we are taking the lead from the European commission, because this is bound to delay action on this important area which is increasingly a matter for concern. It seems like a bit of a cop out to me."

It is unclear whether any of the "aesthetic fillers" such as collagen available in the UK or on the internet are supplied by the company, which cannot be identified for legal reasons. It is also unclear whether collagen made from prisoners' skin is in the research stage or is in production. However, the Guardian has learned that the company has exported collagen products to the UK in the past. An agent told customers it had also exported to the US and European countries, and that it was trying to develop fillers using tissue from aborted foetuses.

Traditional

When formally approached by the Guardian, the agent denied the company was using skin harvested from executed prisoners. However, he had already admitted it was doing precisely this during a number of conversations with a researcher posing as a Hong Kong businessman. The Press Complaints Commission's code of practice permits subterfuge if there is no other means of investigating a matter of public interest.

The agent told the researcher: "A lot of the research is still carried out in the traditional manner using skin from the executed prisoner and aborted foetus." This material, he said, was being bought from "bio tech" companies based in the northern province of Heilongjiang, and was being developed elsewhere in China.

He suggested that the use of skin and other tissues harvested from executed prisoners was not uncommon. "In China it is considered very normal and I was very shocked that western countries can make such a big fuss about this," he said. Speaking from his office in northern China, he added: "The government has put some pressure on all the medical facilities to keep this type of work in low profile."

The agent said his company exported to the west via Hong Kong."We are still in the early days of selling these products, and clients from abroad are quite surprised that China can manufacture the same human collagen for less than 5% of what it costs in the west." Skin from prisoners used to be even less expensive, he said. "Nowadays there is a certain fee that has to be paid to the court."

The agent's admission comes after an inquiry into the cosmetic surgery industry in Britain, commissioned by the Department of Health, pointed to the need for new regulations controlling collagen treatments. Sir Liam Donaldson, the chief medical officer, has highlighted the inquiry's concerns about the use of cadavers for cosmetic treatments. "Cosmetic procedures are a rapidly growing area of private health care," he said. "We must ensure we properly protect patients' safety by improving the training and regulation."

The DoH has agreed to the inquiry's recommendations, but is waiting for the European commission to draw up proposals for laws governing cosmetic products. It could be several years before this legislation takes force.

Meanwhile, cosmetic treatments, including those with with aesthetic fillers, are growing rapidly in popularity, with around 150,000 injections or implants administered each year in the UK. Lip enhancement treatments are one of the most popular, costing an average of £170.

Some fillers are made from cattle or pig tissue, and others from humans. The DoH believes that there may be a risk of transmission of blood-borne viruses and even vCJD from collagen containing human tissue. Although there is as yet no evidence that this has happened, the inquiry found that some collagen injections had triggered inflammatory reactions causing permanent discomfort, scarring and disfigurement. In their report, the inquiry team said that if there was a risk, "action should be taken to protect patient safety through regulation".

While new regulations are to be drawn up, the department is currently powerless to regulate most human-tissue fillers intended for injection or implant, as they occupy a legal grey area. Most products are not governed by regulations controlling medical products, as they are not classified as medicines. They also escape cosmetics regulations, which only apply to substances used on the surface of the skin and not those injected beneath it. The Healthcare Commission is planning new regulations for cosmetic surgery clinics next year, but these will not control the substances used by plastic surgeons.

Hand transplants

A number of plastic surgeons have told the Guardian that they have been hearing rumours about the use of tissue harvested from executed prisoners for several years.

Peter Butler, a consultant plastic surgeon and government adviser, said there had been rumours that Chinese surgeons had performed hand transplants using hands from executed prisoners. One transplant centre was believed to be adjacent to an execution ground. "I can see the utility of it, as they have access and no ethical objection," he said. "The main concern would be infective risk."

Andrew Lee of the University of Pittsburgh School of Medicine, who has visited China to examine transplant techniques, said he had heard similar rumours.

Manufacturers of aesthetic fillers said they had seen Chinese collagen products on sale at trade fairs, but had not seen any labelled Chinese-made in the UK. Dan Cohen, whose US-based company, Inamed, produces collagen products, said: "We have come across Chinese products in the market place. But most products from China are being sold 'off-label' or are being imported illegally."

In China, authorities deny that prisoners' body parts are harvested without their consent. However, there is some evidence to suggest it may be happening.

In June 2001, Wang Guoqi, a Chinese former military physician, told US congressmen he had worked at execution grounds helping surgeons to harvest the organs of more than 100 executed prisoners, without prior consent. The surgeons used converted vans parked near the execution grounds to begin dissecting the bodies, he told the house international relations committee's human rights panel.

Skin was said to be highly valued for the treatment of burn victims, and Dr Wang said that in 1995 he skinned a shot convict's body while the man's heart was still beating. Dr Wang, who was seeking asylum in the US, also alleged that corneas and other body tissue were removed for transplant, and said his hospital, the Tianjin paramilitary police general brigade hospital, sold body parts for profit.

Human rights activists in China have repeatedly claimed that organs have been harvested from the corpses of executed prisoners and sold to surgeons offering transplants to fee-paying foreigners.

Dr Wang's allegations infuriated the Chinese authorities, and in a rare move officials publicly denounced him as a liar. The government said organs were transplanted from executed prisoners only if they and their family gave consent.

Although the exact number of people facing the death penalty in China is an official secret, Amnesty International believes around 3,400 were executed last year, with a further 6,000 on death row.

What is it?

Collagen is a major structural protein found in abundance in skin, bones, tendons and other connective tissue. Matted sheets of collagen give skin its toughness and by winding into molecular "cables", it adds strength to tendons.

What is it used for?

Collagen injections are used in cosmetic surgery to plump up lips and flatten out wrinkles. After botox, collagen injections are the second-most popular cosmetic operations in Britain. Collagen does not have a permanent effect and several injections are often needed.

What else is it good for?

Collagen was being put to good use as far back as the stone age. Neolithic cave dwellers around the Dead Sea are believed to have used it as a primitive form of glue some 8,000 years ago. More recently, researchers have developed a form that can be poured or injected into wounds to seal them.

Where does it come from?

A number of sources. Some companies extract it from cow skin and treat it to minimise the risk of allergic reactions or infection. Others collect it from human donors or extract cells from the patient before growing the necessary amount in a laboratory.

Is it safe?

Collagen can cause allergic reactions if it has not been treated correctly, and there is a theoretical risk of disease being passed on. A small amount of collagen is often injected into the skin a few weeks before treatment to test for possible allergic reactions. Earlier this year, Sir Liam Donaldson warned that collagen injections could spread conditions such as hepatitis and variant CJD, the human form of mad cow disease.

http://www.guardian.co.uk/uk_news/story/0,,1568467,00.html




Opinion of the BIOHAZ Panel on the safety of collagen and a processing method for the production of collagen
Last updated: 26 April 2005
Adopted on 26 January 2005 (Question N° EFSA-Q-2004-085)

Opinion
http://www.efsa.eu.int/science/biohaz/biohaz_opinions/849/opinion_safety_collagen2.pdf
Summary
http://www.efsa.eu.int/science/biohaz/biohaz_opinions/849/summary_safety_collagen2.pdf
Summary

Chapter 4, Section B, Part V(1) of the Annex II of the Council Directive 92/118/EEC, amended by the Decision 2003/721/EC, specifies that collagen must be produced using a process that ensures that the raw material is subjected to a treatment involving washing, pH adjustment using acid or alkali followed by one or more rinses, filtration and extrusion; or by an equivalent process approved by the European Commission (EC) after consultation of the appropriate Scientific Committee.


The company concerned, hereafter named 'the company' uses a different process (hydrolysis), whose resulting hydrolysed collagen apparently cannot be extruded due to its low molecular weight. The company's process complies with the rest of the production process specified in Part V(1) of the Decision 2003/721/EC. Consequently the EC has asked the European Food Safety Authority (EFSA) to evaluate, from biological risk perspectives, the data presented.


The company collects poultry and pig bone at registered premises of the meat industry which are supervised by veterinary authorities. The bones comply with the demands of Decision 2003/721/EC, and are declared fit for human consumption. The manufacturing process contains several steps of which is known that they can remove or inactivate Transmissible Spongiform Encephalopathy (TSE) infectivity. The TSE inactivation by the entire process is conservatively estimated 5 logs.


Considering the information provided by the company it is concluded that the production process proposed by the industry ensures equivalent or higher health safety of collagen intended for human consumption compared to the safety achieved by applying the standards of Part V(1) of Decision 2003/721/EC.

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Cosmetic Ingredients:
Understanding the Puffery
by Judith E. Foulke

The lotion contained bovine albumin and the label claimed it would give a "face lift without surgery." The Food and Drug Administration said the claims caused the product to be a misbranded drug. In 1968, the court said no. "If lifting and firming products are deemed intended to affect the structure of the body, girdles and brassieres must be devices within the meaning of the law."

In 1969 an appellate court overturned this decision, but the issues persist today. "Most cosmetics contain ingredients that are promoted with exaggerated claims of beauty or long-lasting effects to create an image," says John E. Bailey, Ph.D., director of FDA's division of color and cosmetics. "Image is what the cosmetic industry sells through its products, and it's up to the consumer to believe it or not," Bailey says.

In the past, cosmetic manufacturers have depended upon mysterious "gimmick" additives, such as turtle oil to promote skin rejuvenation or tighten chin muscles, shark oil, queen bee royal jelly, chick embryo extract, horse blood serum, and pigskin extracts.

Promotion of these "gimmick" additives, combined with today's more sophisticated cosmetic ingredients, is what Bailey and the cosmetic industry call "puffery."

The argument is sometimes made that while Congress intended to safeguard the health and economic interests of consumers with the Federal Food, Drug, and Cosmetic Act, it also meant to protect a manufacturer's right to market a product free of excessive government regulation. And, in an industry that sells personal image, especially images of beauty and sex appeal, not allowing the puffery claims would certainly hurt the marketing, says Bailey.

But there's hope for credibility in claims for cosmetic ingredients. Some of the more responsible cosmetic firms are rethinking their claims that push believability to its outside edge. Linda Allen Schoen of Neutrogena says that today's more knowledgeable consumer wants "facts versus puffery--products based on skin care realities, promises banked on achievable benefits." Besides, says Schoen, limited recession dollars tend to be spent on products consumers can trust.

Still, with the exception of colors and certain prohibited ingredients, a cosmetic manufacturer may use essentially any raw material in a product and market it without prior FDA approval. The prohibited ingredients are biothionol, hexachlorophene, mercury compounds (except as preservatives in eye cosmetics), vinyl chloride and zirconium salts in aerosol products, halogenated salicylanilides, chloroform, and methylene chloride.

Federal regulations require ingredients to be listed on product labels in descending order by quantity, but often the list is not user-friendly. Because cosmetic ingredients are often complex chemical substances, the list may be incomprehensible to the product's average user. (See "Cosmetic Safety: More Complex Than at First Blush" in the November 1991 FDA Consumer.) However, if the same name is used by all manufacturers, consumers can compare different products and make reasonable value judgments.

Although cosmetic claims, even those considered "puffery," are allowed without scientific substantiation, if a cosmetic makes a medical claim, such as removing dandruff, the product is regulated as an over-the-counter drug for which scientific studies demonstrating safety and effectiveness must be submitted to FDA.

Baffling Names

Because of the unusual and sometimes bewildering nature of some ingredients in cosmetics, consumers often ask FDA for explanations. "My night cream contains liposomes--what is that?" "Why is placenta used in cosmetics--is it human placenta, and could I get a disease from it?" "What are cerebrosides and ceremides?"

FDA cosmetic scientists can explain the nature of an ingredient when it is identified by its chemical name. But when an ingredient is listed by its trade name, FDA usually must consult the manufacturer's trade literature or the International Cosmetic Ingredient Dictionary, published by the Cosmetic, Toiletry, and Fragrance Association, Inc., the industry's major trade association. The dictionary, now in its fourth edition, provides a uniform system for assigning ingredient names. FDA currently recognizes the second edition as a primary reference.

Here is what FDA knows about some currently marketed ingredients:

Liposomes are microscopic sacs, or spheres, manufactured from a variety of fatty substances, including phospholipids. While phospholipids are natural components of cell membranes, the material actually used in cosmetics may be obtained either from natural or synthetic sources. When properly mixed with water, phospholipids form liposome spheres, which can "trap" any substance that will dissolve in water or oil.

Manufacturers say that liposomes act like a delivery system. They claim that, when present in a cream or lotion, liposomes can more easily penetrate the surface skin to underlying layers, "melt," and deposit other ingredients of the product.

Nayad is a trade name for yeast extract. The manufacturer's literature describes Nayad as a "new system that takes yeast cells and refines them hundreds of times.... What results is a highly concentrated, odor-free, unusually potent yeast extract ...." The same literature reports that "no one really knows how Nayad is working in the skin; all we know for certain is the way it makes the skin look and feel. Test subjects report a noticeable smoothing of lines and wrinkles." FDA has no data to either substantiate or refute these claims.

Vitamins are added to cosmetics by manufacturers because foods containing vitamins A, D, E, K, and some of the B complex group are necessary in diets to maintain healthy skin and hair. Using these vitamins in cosmetics that are applied to the skin surface implies that skin will be nourished by them.

But Stanley R. Milstein, Ph.D., associate director for FDA's cosmetics division, says the notion that skin can be nourished by a vitamin applied to its surface has not been proven clinically. For that reason, says Milstein, a vitamin added to a cosmetic product must be listed in the ingredient label by its chemical name so that it doesn't convey a misleading message. However, FDA does not prohibit listing vitamins by their common names on the principal display panel of a cosmetic as long as the consumer is not misled and no therapeutic claims are made.

Some leaders in the cosmetic industry, such as Neutrogena's Schoen, agree with the FDA position on vitamins in skin care products. Others, such as Chris Vaughn of Sun Pharmaceuticals, Ltd., cite clinical studies done by Hoffmann-La Roche and others that show that vitamins can penetrate layers of skin and have beneficial effects. This, however, would make it a drug use, and manufacturers who use vitamins in their products don't usually make claims that would cause their products to be classified as drugs. Vaughn says that getting a drug classification is time-consuming and expensive, and in his opinion not justifiable because the informed consumer understands the beneficial properties of vitamins.

Although the debate about the value of vitamins in skin care products continues, it is generally accepted that a sufficient quantity of vitamin E (shown on ingredient lists as tocopherol), an antioxidant, preserves the fatty components in cosmetic creams and lotions to prevent off-color and off-odors.

Aloe vera is a plant from the lily family whose anti-irritant properties have been recognized since before the days of Cleopatra. It is listed as an ingredient in many skin lotions, but it would take much more aloe vera than most products contain for the anti-irritant properties to work.

Milstein explains that aloe vera, as a cosmetic ingredient, is expensive because it requires delicate processing and handling. A product that contains the 5 to 10 percent aloe vera necessary for the anti-irritant properties to be effective would send the price out of range for many consumers.

What About Biological Ingredients?

A number of biological products in cosmetics have raised consumer concern:

Human placenta is the nourishing lining of the womb (uterus), which is expelled after birth. When placental materials were first used as cosmetic ingredients in the 1940s, manufacturers promoted the products as providing beneficial hormonal effects such as stimulating tissue growth and removing wrinkles. (Although newborn infants emerge from the womb with wrinkled skin!) The hormone content and the tissue-growth and wrinkle-removing claims classified the placenta-containing products as drugs, and FDA declared them to be ineffective and therefore misbranded.

FDA's challenge caused placenta suppliers to change marketing strategies by claiming that hormones in their placenta ingredients had been extracted and were no longer in the product. They then offered placental raw materials without medical claims--only as a source of protein.

Can you get a disease from placental cosmetic ingredients? Bailey says no. Placenta used in cosmetics is washed and processed many times to destroy any harmful bacteria or viruses. Besides that, says Bailey, the cosmetic matrix (components that bind the ingredients in products) is made from a wide variety of substances, such as alcohol and preservatives, that would present a hostile environment to any viruses or bacteria the placenta might have carried.

Amniotic liquid (from cow or ox) is the fluid that surrounds the developing fetus and protects it from physical injury. It is promoted for benefits similar to those of human placenta and has limited use in moisturizers, hair lotions, scalp treatments, and shampoos.

Collagen (from young cows) is the protein substance found in connective tissue. (Connective tissue binds together and supports organs and other body structures.) A great deal of research has been done on the different types and uses for collagen. In cosmetics, collagen has a moisturizing effect. It is not water soluble, but it holds water. FDA says there is no convincing evidence that collagen can penetrate the skin and have an effect below the surface.

Cerebrosides (from animals or plants) are a type of glycolipid (a chemically combined form of fatty substance and carbohydrate) produced naturally in basal epidermal cells--the deepest layer of skin. After cerebrosides are formed, they are secreted to the outside of the cells and serve as a protective coating. As new cells form in lower layers of skin, the older skin cells move closer to surface layers and start to dry out. During this process, the cerebrosides are chemically changed and form ceramides, part of a network of membranes between cells. Skin moisture and suppleness comes from this network.

The raw material for cerebrosides in cosmetics comes from cattle, oxen or swine brain cells or other nervous system tissues. Alternatively, the raw material may be isolated from plant sources. Industry cosmetic scientists claim that the use of cerebrosides in skin products results in a smoother skin surface and better moisture retention, effects that translate into marketing claims such as luminosity and ever-improving hydration. FDA has not evaluated the studies on which these claims are based.

Industry Self-Regulation

"The cosmetic industry is sensitive to the image of an uncontrolled market where anything goes," says Bailey. "They counter this image with well-established self-regulation programs. Part of the incentive for such industry policy is to avoid increased regulatory authority."

The most well-known of industry-sponsored self-regulation is the Cosmetic Ingredient Review, sponsored by the Cosmetic Toiletry and Fragrance Association. The CIR is accomplished by a panel of scientific and medical experts who evaluate cosmetic ingredients for safety and publish detailed reviews of available safety data. "A finding of safety by the CIR provides a degree of confidence that the ingredient can safely be used in cosmetics," Bailey says. "In the absence of the CIR program, there would be no systematic examination of the safety of individual cosmetic ingredients." FDA has no statutory authority to require that the data be submitted to the agency.

FDA encourages industry cooperation through its cosmetic voluntary reporting program. Cosmetic firms registered in the program voluntarily report manufacturing and formulation information, along with product experience data, to FDA. Adverse reactions such as skin irritations are also reported. Using this information, FDA can determine a baseline reaction rate for specific product categories such as hair coloring or eye makeup preparations. The agency gives participating companies this baseline information so they can compare their own adverse reaction rates to the FDA-established baseline.

"Registration in this voluntary program does not mean that FDA approves or endorses a firm, raw material, or product," says Mary Waleski, chief of the cosmetic registration program. "But it does provide for an interaction between the industry and government for exchange of information."

FDA would like to see wider industry participation. "Based on the number of companies we think are eligible to participate, only about 35 percent do," Waleski says. There are also other problems. "Sometimes the information a firm submits is incomplete," Waleski says. "And if a firm does not update its submissions with additions or deletions, the information in the registration files could accumulate as inaccurate information."

FDA continues to explore ways to make the program more useful for both industry and government, says Bailey. "We compare product information available to the agency with registered data, and now we're considering periodic field surveys of products on the shelves. Such a review would include comparison of label ingredient declarations with information reported to FDA."

The quest for sustained youth and beauty that sells cosmetics is age-old, though ingredients used to achieve that image may change. Shakespeare noted the same concern that keeps the cosmetic industry going when he said,


Time doth transfix the flourish set on youth
And delves the parallels in beauty's brow.

But he gave voice to another standard when he wrote,


To me, fair friend, you never can be old,
For as you were when first your eye I eyed,
Such seems your beauty still.

Judith Foulke is a staff writer for FDA Consumer.

Publication No. (FDA) 95-5013

http://www.fda.gov/fdac/reprints/puffery.html



Coverage of Bovine-Derived Ingredients for Bovine Spongiform Encephalopathy (BSE)
By letter dated May 9, 1996 (ATTACHMENT C), FDA recommended that firms that manufacture or import cosmetic products and their ingredients containing specific bovine tissues, including extracts or substances derived from such tissues, take whatever steps necessary to assure themselves that such ingredients do not come from cattle born, raised, or slaughtered in countries where bovine spongiform encephalopathy (BSE) exists. BSE is a fatal transmissible spongiform encephalopathy similar to Creutzfeldt-Jakob disease in humans.

BSE continues to be prevalent in Great Britain (including Northern Ireland and the Falklands), Belgium, Luxenbourg, the Netherlands, France, Switzerland, Republic of Ireland, Oman, and Portugal. This list of BSE countries is subject to change. Refer to I.A. #17-04 for the most up-to-date list.

Manufacturers and importers of cosmetic products and their ingredients should have planned, systematic Procedures in place to provide assurances to themselves and to consumers that bovine-derived tissues do not come from cattle in countries where BSE occurs.

NOTE: The list of tissues contained in the Agency's 5/9/96 letter has been expanded (ATTACHMENT B) to include additional bovine tissue or tissue-derived ingredients with a suspected risk of infectivity. The tissues and tissue derived-ingredients marked with asterisks are considered to present the highest risk of infectivity (hereinafter referred to as high-risk tissues).

http://www.cfsan.fda.gov/~comm/cp29002.html


USF Ointment® STANDARD PROCESS INC.
Ingredients: Lard, lanolin, linseed oil, soybean lecithin, beeswax, bovine orchic glandular extract, and fragrance.

http://www.standardprocess.com/sp_catalog_product_detail.asp



CATRIX® 5 Rejuvenation Cream


Active Ingredients (SPF 15 Cream only): Ethylhexyl-P- Methoxycinnamate 7.5%, Oxybenzone 5%, Titanium Dioxide 2%

Ingredients: Water, Isopropyl Palmitate, Catrix® Cartilage, C12-15 Alkyl Benzoate, Cetyl Alcohol, Hydrogenated Vegetable Oil, Aloe Barbadensis Gel, PEG-100 Stearate, Algae Extract, Tocopheryl Acetate, Matricaria (Chamomilla Recutita) Extract, Apple (Pyrus Malus) Extract, Kola (Cola Accuminata) Extract, Bisabolol, Polysorbate 60, Phospholipids, Steareth-2, Butylene Glycol, Xanthan Gum, Magnesium Aluminum Silicate, Orange (Citrus Aurantium Dulcis) Oil, Triethanolamine, Dimethicone, Disodium EDTA, Phenoxyethanol, Methylparaben, Ethylparaben, Propylparaben, Butylparaben, Potassium Sorbate

Catrix® is a bovine-derived complex mucopolysaccharide product.



CATRIX® 10 Ointment



CATRIX® 10 Ointment

Catrix 10 Ointment is a professional strength topical application containing 10% Catrix powder in a petrolatum base.

Catrix 10 Ointment is a clinically-tested and specially-formulated post-procedure application designed to help relieve discomfort and restore skin to its natural healthy condition following laser resurfacing, chemical peels and dermabrasions.

Catrix 10 Ointment provides important benefits for patients who undergo these therapies.

1. Expedites the development of epithelial cells, helping the patient to heal faster.

2. Relieves the discomfort experienced post-procedure:

Reduces redness
Soothes itchiness
Reduces erythema
Controls oozing and crusting
Limits tautness
Faster healing with increased comfort - that's the Catrix 10 Ointment advantage.

For surgical incisions and other wounds Catrix 10 is equally effective. It applies easily with no patient discomfort, and provides a moist environment important to proper healing. This non-irritating formula is also an effective therapy for diaper rash, skin problems resulting from incontinence, abrasions, burns and psoriasis.

Directions: Liberally apply a layer immediately following the dermatological procedure and whenever treated area feels or looks dry (every 2-5 hrs.). In the unlikely event of crust formation, gently soak off using water and a soft cloth; then reapply Catrix 10 Ointment.

Important: keep skin moist with Catrix 10 Ointment at all times for increased comfort and speed in healing.

For other uses, apply frequently as directed by a skin care professional.

Ingredients: Petrolatum, Catrix® Cartilage, Isopropyl Palmitate, Beeswax, Parafin, Benzyl Alcohol

Catrix® is a bovine-derived complex mucopolysaccharide product.


http://www.catrix.com/products/catrix10.html


Placenta Wrinkle Cream is a rich moisture cream containing essential vitamins, minerals and sheep placenta that helps to nourish the skin, accelerates tissue regeneration and improves absorption of moisture. Australian sheep placenta is known to be one of the best.

Placenta Cream (skin oil) has been fortified with collagen and liposomes to nourish your skin as a day and night cream.

We suggest to use Placenta Cream daily if you wish to have a younger looking skin. Liposomes is one of the newest discoveries in skin care and used in the most sophisticated creans today.

Suggested use:
Massage gently a small amount with fingertips into face at night and moming. Excellent as a make-up base.

Placenta Wrinkle Moisture Cream is suggested for all types of skin for women and men.

Ingredients:
Deionized water, stearic acid, safflower oil, Cetyl alcohol, glyceryl stearate PEG-100 stearate, propytene glcol, triethanolamine, almond oil, rose hips oil, placenta extract, tocopheryl acetate (vitamin E acetate). Retinyl palmitate (vitamin A palmitate). Hydrolyzed protin, Panthenol, lecithin (and) superoxide dismutase, bht, methylparaben. Tetrasodium EDT, imidazolidinyl urea, fragrance.

http://store.yahoo.com/vitasprings/placenta-wrinkle-cream-skin-oil-.html



July 14, 2004



An Evaluation of the Risk of Variant Creutzfeldt-Jakob Disease from Exposure to Cattle-Derived Protein Used in Cosmetics
Introduction
The discovery of a cow with bovine spongiform encephalopathy (BSE) in Washington State in December 2003 triggered action to put in place additional safeguards against BSE. Even though the cow was born in Canada, the fact that the cow was discovered in the U.S. and had been sent to slaughter and rendering before it was identified as positive indicates a vulnerability in the U.S. BSE protective net.

While BSE is usually identified with either food safety or animal health, cosmetics, because of the ways they are used, provide another route for BSE infectivity to enter the human system. Cosmetics may contain a wide range of cattle-derived ingredients, many of which may carry the BSE agent. FDA prepared this assessment of the risks to public health if cattle-derived ingredients are used in cosmetics.

This qualitative risk assessment follows the generally accepted framework for risk assessments endorsed by the Codex Alimentarious Commission, the U.S. National Academy of Sciences, and other authoritative bodies. The framework divides risk assessment into four components: (1) hazard identification, (2) exposure assessment, (3) hazard characterization (or dose-response assessment), and (4) risk characterization. The risk assessment uses scientific evidence to the extent that it exists. The agency has determined that this qualitative risk assessment is appropriate to the circumstances.

Risk Assessment
Hazard Identification
In April 1996, British scientists reported a previously undetected new variant of Creutzfeldt-Jakob disease (vCJD) in young patients, with symptoms somewhat different from sporadic CJD (Refs. 1 and 2). All cases of vCJD had histopathologic evidence of spongiform changes in the brain, but also showed formation of "florid" plaques (a core of amyloid protein with surrounding halos of vacuoles) not typically seen in other forms of CJD (Ref. 3). Clinically, vCJD usually begins with a psychiatric presentation, such as depression, anxiety, nightmares or hallucinations. These symptoms are followed by memory impairment, then dementia in the late stages. The clinical course may last up to two years before death occurs (Ref. 4). Because scientific evidence suggests that the presence and infectivity of abnormal prion proteins in vCJD share characteristics with abnormal prion proteins found in cattle with BSE, scientists have concluded that exposure to the BSE agent is the most plausible explanation for the occurrence of vCJD (Refs. 5 - 8). Monkeys (genetically the closest animal model to humans) inoculated with samples of brain from BSE-infected cattle have been found to develop a TSE that is histopathologically similar to vCJD (Ref. 9), as have mice inoculated or fed with BSE-infected tissue (Ref. 10). In addition, studies have shown that abnormal prion proteins from vCJD patients are molecularly similar to abnormal prion proteins from BSE-infected cattle and different from abnormal prion proteins from patients with CJD and other spongiform encephalopathies (Ref. 4).

Prions are predominantly found in the central nervous system, portions of the intestine, and tonsils of cattle with BSE. Cosmetic ingredients can be derived from some of these tissues. Although large prion doses are known to have a shorter incubation period before the disease develops, even low doses may cause vCJD if infectious prions survive digestion and the host survives long enough to complete a longer incubation period. Although most scientists believe that vCJD in humans is caused by consumption of cattle-derived food products contaminated with the agent that causes BSE (Refs. 11-14), exposure from cosmetics derived from cattle protein is another potential route of exposure.

Exposure Assessment
BSE in the United States
On December 23, 2003, USDA diagnosed a positive case of BSE in an adult Holstein cow in the State of Washington.

Use of Cattle Protein in Cosmetics
Cosmetics may be made from a variety of cattle-derived ingredients. These ingredients include albumin, brain extract, brain lipid, cholesterol, fibronectin, sphingolipids, collagen, keratin, and tallow and tallow derivatives. However, tallow derivatives, particularly fatty acids and glycerin, are the predominant bovine ingredient used by the cosmetic industry and contain very little protein, and are therefore unlikely vehicles for the transmission of prions. Cattle-derived ingredients serve many functions and may be used as skin conditioning agents, emollients, binders, and hair and nail conditioning agents.

Absorption of Prions from Cosmetics
There are several routes through which cosmetics contaminated with the agent that causes BSE could transmit disease to humans. Transmission of the BSE agent to humans through intact skin is believed to be unlikely; however, cosmetics may be ingested or applied to cut or abraded skin or to conjunctival tissues that can provide direct routes for infection.

It is well-documented that central nervous system tissue, including the optic nerve, carries infectivity in animals with TSEs and humans with vCJD, and serves as an efficient route of transmission. In mice, intraocular injection of scrapie caused infection along the optic nerve, which eventually spread into non-neural tissue via the lymphatic system (Ref. 15). In addition to intraocular injection, infectivity has been transmitted to animals via the conjunctiva of the eye (mucosal tissue). Scott et al. (Ref. 16) found that scrapie was induced in 42 percent of rodents by dropping a high concentration of infectivity onto the conjunctiva. Klitzman et al. (Ref. 17) suggested that kuru, a human TSE disease found only among the Fore people of New Guinea, might have been transmitted by rubbing infected human brain into eyes or cut skin, while handling and consuming infected brain during funeral rituals.

Cut or abraded skin also has been proposed as a route for contracting TSE diseases. The transmission of kuru through cut skin has been suggested and was mentioned previously. Taylor et al. (Ref. 18) and Ingrosso et al. (Ref. 19) demonstrated increased transmission of scrapie via oral mucosal tissue. In one study, 100 percent of mice with experimentally damaged oral mucosal tissue developed scrapie through ingestion of infected material, while only 71 percent of mice with intact mucosa developed the disease (Ref. 18). In addition, Pammer et al. (Ref. 20) and Sugaya et al. (Ref. 21) noted that epithelial cells, dendritic cells, and keratinocytes (the primary cell types found in the epidermis) have been found to contain infectious prion protein, indicating that these cells are potential targets for peripheral infection with a TSE disease.

Use of BSE-contaminated cosmetics could provide a means of human infection via several routes discussed above. Many cosmetics are typically applied in the area of the eye (mascara, eye brow pencil, eyeliner, eye lotion, and eye makeup remover) and almost any cosmetic, including shampoo, can get into the eye via eye rubbing or incorrect application. Any cosmetic product, but particularly shaving creams and gels and lotions, may be applied to cut or abraded skin. Cosmetics that are ingested, such as lipstick, dentifrices, mouthwash, and breath fresheners, would have an oral route of infection, and the ingested fraction would have the same risk as prion-contaminated meat and other food products derived form cattle. Furthermore, the presence of cattle derived ingredients is not generally obvious to the consumer, since the source of the ingredient (i.e. cattle derived) does not need to be placed on the label.

Hazard Characterization
Prions with a particular abnormal tertiary structure are apparently able to generate a similar misconformation in normal proteins, which can in turn cause further misconformations. This allows propagation of the disease and is also important for understanding the relationship between dose, response, and the incubation required for the disease to develop. Once the prions have entered the brain, the prion concentration grows with a relationship that has been described as exponential (Ref. 14).

In cattle, there is a minimal incubation period of six months to a year required for the development of the disease, regardless of the size of the initial dose, although incubation periods of 4 or more years appear to be more common (Refs. 11 and 12). The lag period may reflect the fact that transmission from food to brain may be preceded by symptomless amplification of infectious prions in the intestine and lymphoreticular tissues. While cattle at this stage would be clinically normal and may have negative BSE test results, various tissues could be infectious (Refs. 11 and 12).

Despite widespread exposure in the U.K. to BSE-contaminated meat products, only a very small percentage of the exposed population has been diagnosed with vCJD to date. However, ongoing experiments indicate that the infectious dose for cattle is very low. One gram of affected bovine brain homogenate is sufficient to cause BSE in more than 50 percent of calves exposed by mouth. Five years after oral consumption of lower doses of brain material, 2 of 15 calves fed 0.1 gram had onset of BSE, and 1 of 15 fed 0.01 gram had developed the disease. This experiment is ongoing (Ref. 22). There is thought to be a 10- to 10,000-fold increase in the amount of infectious material needed to cause illness in humans as compared with cattle, because of the species barrier (Ref. 23).

Risk Characterization
This is not a quantitative risk assessment. However, it does sketch out the logical structure that a quantitative model could use if one were constructed. Some conclusions can be drawn without a quantitative analysis. Since there is considerable uncertainty associated with the premises outlined in the present analysis, it follows that there will also be considerable uncertainty associated with the risk estimate. In the exposure assessment, there are considerable uncertainties associated with the origin of protein used in making cosmetics, the effect of processing on prion concentration, and the transmission rates for dermal and ocular exposure. Particularly large uncertainties associated with the dose response assessment include the magnitude of the species barrier and the length of the incubation period.

With exception of the uncertainty associated with estimates of the dermal and ocular transmission rates, most of the uncertainties associated with a risk assessment of BSE prions in cosmetics are also associated with the risk from food consumption. For example, the number of BSE-affected cattle and the variability in human susceptibility will impact the risk of both food- and cosmetic-associated vCJD.

Some of these uncertainties may concomitantly affect both sides of a cost-benefit analysis. In particular, if there is not substantial use of cattle-derived protein in making cosmetics, then there will be little exposure, and also little economic consequence from regulating use. Conversely, high use would require substantial substitution and alternative means of animal-by-product disposal.

Conclusions
A form of spongiform encephalopathy that occurs in humans (vCJD) is thought to result from the same protein (a prion) that causes BSE in cattle. Although the primary source of exposure is likely to be due to the ingestion of beef and other food derived from cattle, other routes of exposure may also be important. Although small doses require longer incubation periods for clinical signs to develop, small doses of infectious prions can potentially cause disease. Cosmetics that contain protein derived from bovine sources are a potential source of exposure. It has been demonstrated experimentally that TSEs may result from ocular absorption of protein, and systemic absorption of protein may also occur when cosmetics are applied to lacerated or abraded skin. As a result, it may be concluded that there is some risk of occurrence of vCJD from the use of cattle-derived protein in cosmetics. However, since there are large uncertainties associated with the quantitative estimates of many of the important variables, any quantitative estimate of the risk or rate at which the disease may be expected to occur would be correspondingly imprecise.

The risk of BSE from cosmetics may be reduced through the control of exposure. Aside from the derivation processes used on tallow, the effectiveness of cosmetic manufacturing processes for inactivating BSE prions is unknown. The surest way to prevent transmission of BSE-prion through cosmetics is to avoid the use of high-risk cattle-derived protein in the manufacture of cosmetics.

References
Will, R.G., J.W. Ironside, M. Zeidler, S.N. Cousens, K. Estibeiro, A. Alperovitch, S. Poser, M. Pocchiari, A. Hofman, and P.G. Smith. 1996. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347: 921-25.

Chazot, G., E. Broussolle, C.I. Lapras, T. Blattler, A. Aguzzi, and N. Kopp. 1996. New variant of Creutzfeldt-Jakob disease in a 26-year-old French man. Lancet 347: 1181.

Prusiner, S.B. 2001. Shattuck Lecture--Neurodegenerative diseases and prions. N Engl J Med 344 (20): 1516-1526.

Collinge, J. 2001. Prion diseases of humans and animals: Their causes and molecular basis. Annu. Rev. Neurosci. 24: 519-50.

Almond, J. and J. Pattison. 1997. Human BSE. Nature 389: 437-38.

Scott, M.R., R. Will, J. Ironside, H-O.B Nguyen, P. Tremblay, S.J. DeArmond, and S.B. Prusiner. 1999. Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc. Natl. Acad. Sci. 96 (26): 15137-142.

Hill, A.F., M. Desbruslais, S. Joiner, K.C.L. Sidle, I. Gowland, J. Collinge L.J. Doey, and P. Lantos. 1997. The same prion strain causes vCJD and BSE. Nature 389: 448-450.

Collinge, J. 1999. Variant Creutzfeldt-Jakob disease. Lancet 354: 317-323.

Lasmezas, C.I., J-G. Fournier, V. Nouvel, H. Boe, D. Marce, F. Lamoury, N. Kopp, J-J. Hauw, J. Ironside, M. Bruce, D. Dormont and J-P. Deslys. 2001. Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-Jakob disease: Implications for human health. Proc. Natl. Acad. Sci. 98 (7): 4142-4147.

Bruce, M.E., R.G. Will, J. W. Ironside, I. McConnell, D. Drummond, A. Suttie, L. McCardle, A. Chree, J. Hope, C. Birkett, S. Cousens, H. Fraser, and C.J. Bostock. 1997. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 389: 498-501.

Brown, P. 1997. The risk of bovine spongiform encephalopathy ('mad cow disease') to human health. J. Am. Med. Assn. 278 (12): 1008-1011.

Brown, P., R.G. Will, R. Bradley, D.M. Asher, and L. Detwiler. 2001. Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: Background, evolution, and current concerns. Emerging Infect. Dis. 7 (1): 6-16.

Scientific Steering Committee, European Commission. 1999. Opinion of the Scientific Steering Committee on the Human Exposure Risk (HER) via food with respect to BSE. Accessed online at http://europa.eu.int/comm/food/fs/bse/scientific_advice08_en.html.

Harvard Center for Risk Analysis, Harvard School of Public Health. 2003. Evaluation of the potential for bovine spongiform encephalopathy in the United States. Accessed online at http://www.hcra.harvard.edu/pdf/madcow.pdf.

Fraser, J.R. 1996. Infectivity in extraneural tissues following intraocular scrapie infection. J. Gen. Virol. 77: 2663-68.

Scott, J.R., J. D. Foster and H. Fraser. 1993. Conjunctival instillation of scrapie in mice can produce disease. Vet Microbiol 34 (4): 305-309.

Klitzman R.L., M.P. Alpers, and D.C. Gajdusek. 1984. The natural incubation period of kuru and the episodes of transmission in three clusters of patients. Neuroepidemiology 3 (1): 3-20.

Taylor, D.M., I. McConnell, and H. Fraser. 1996. Scrapie infection can be established readily through skin scarification in immunocompetent but not immunodeficient mice. J. Gen. Virol. 77: 1595-99.

Ingrosso, L., F. Pisani, and M. Pocchiari. 1999. Transmission of the 263K scrapie strain by the dental route. J. Gen. Virol. 80: 3043-47.

Pammer, J., W. Weninger, and E. Tschachler. 1998. Human keratinocytes express cellular prion-related protein in vitro and during inflammatory skin diseases. Am. J. Pathol. 153: 1353-58.

Sugaya, M., K. Nakamura, T. Watanabe, A. Asahina, N. Yasaka, Y. Koyama, M. Kusubata, Y. Ushiki, K. Kimura, A. Morooka, S. Irie, T. Yokoyama, K. Inoue, S. Itohara, and K. Tamaki. 2002. Expression of cellular prion-related protein by murine Langerhans cells and keratinocytes. J. Dermato. Sci. 28: 126-134.

Vossen, P., J. Kreysa, and M. Goll. 2003. Overview of the BSE risk assessment of the European Commission's Scientific Steering Committee (SSC) and it TSE/BSE ad hoc group. Accessed online at http://europa.eu.int/comm/food/fs/sc/ssc/out364_en.pdf.

Scientific Steering Committee, European Commission. 2000. Oral exposure of humans to the BSE agent: Infective dose and species barrier. Accessed online at http://europa.eu.int/comm/food/fs/sc/ssc/out79_en.pdf.


http://www.cfsan.fda.gov/~comm/bse-ra.html



Journal of Virology, February 2005, p. 1888-1897, Vol. 79, No. 3


Neuroinvasion by Scrapie following Inoculation via the Skin Is
Independent of Migratory Langerhans Cells

Joanne Mohan, Moira E. Bruce, and Neil A. Mabbott*

Neuropathogenesis Unit, Institute for Animal Health, Edinburgh, Scotland, United Kingdom

Received 18 June 2004/ Accepted 7 September 2004

Many natural transmissible spongiform encephalopathy (TSE) i

 

[flounder]

Journal of Virology, February 2005, p. 1888-1897, Vol. 79, No. 3


Neuroinvasion by Scrapie following Inoculation via the Skin Is
Independent of Migratory Langerhans Cells

Joanne Mohan, Moira E. Bruce, and Neil A. Mabbott*

Neuropathogenesis Unit, Institute for Animal Health, Edinburgh, Scotland, United Kingdom

Received 18 June 2004/ Accepted 7 September 2004

Many natural transmissible spongiform encephalopathy (TSE) infections are likely to be acquired peripherally, and studies in mice show that skin scarification is an effective means of scrapie transmission. After peripheral exposure, TSE agents usually accumulate in lymphoid tissues before spreading to the brain. The mechanisms of TSE transport to lymphoid tissues are not known. Langerhans cells (LCs) reside in the epidermis and migrate to the draining lymph node after encountering antigen. To investigate the potential role of LCs in scrapie transportation from the skin, we utilized mouse models in which their migration was blocked either due to CD40 ligand deficiency (CD40L/ mice) or after caspase-1 inhibition. We show that the early accumulation of scrapie infectivity in the draining lymph node and subsequent neuroinvasion was not impaired in mice with blocked LC migration. Thus, LCs are not involved in TSE transport from the skin. After intracerebral inoculation with scrapie, wild-type mice and CD40L/ mice develop clinical disease with similar incubation periods. However, after inoculation via skin scarification CD40L/ mice develop disease significantly earlier than do wild-type mice. The shorter incubation period in CD40L/ mice is unexpected and suggests that a CD40L-dependent mechanism is involved in impeding scrapie pathogenesis. In vitro studies demonstrated that LCs have the potential to acquire and degrade protease-resistant prion protein, which is thought to be a component of the infectious agent. Taken together, these data suggest that LCs are not involved in scrapie transport to draining lymphoid tissues but might have the potential to degrade scrapie in the skin.

------------------------------------------------------------------------
* Corresponding author. Mailing address: Institute for Animal Health, Neuropathogenesis Unit, Ogston Bldg., West Mains Rd., Edinburgh EH9 3JF, United Kingdom. Phone: 44(0)131-667-5204. Fax: 44(0)131-668-3872. E-mail: [email protected]. .

------------------------------------------------------------------------
Journal of Virology, February 2005, p. 1888-1897, Vol. 79, No. 3
0022-538X/05/$08.00+0 DOI: 10.1128/JVI.79.3.1888-1897.2005
Copyright © 2005 , American Society for Microbiology . All Rights Reserved.

http://jvi.asm.org/cgi/content/abst...journalcode=jvi


hmmm, cosmetics ingredients and CJD via animal TSEs ????

RUB A DUB DUB, A TSE IN THAT TUB OF CREAM OR EYE LINER ???

kuru infection via open wounds etc. , accumulation ???

just thinking out loud here...

what does the fda say, everything is ok, but what about before July 14, 2004 ???

WHAT about all that cream and eye make-up my mother used for decades and she
had the Heidenhain Variant of CJD WHICH is in the brain directly behind the eyes,
causing you to go blind first? she rubbed the stuff on her face and arms for as long as
i can remember, every night...


Conclusions

A form of spongiform encephalopathy that occurs in humans (vCJD) is thought to result from the same protein (a prion) that causes BSE in cattle. Although the primary source of exposure is likely to be due to the ingestion of beef and other food derived from cattle, other routes of exposure may also be important. Although small doses require longer incubation periods for clinical signs to develop, small doses of infectious prions can potentially cause disease. Cosmetics that contain protein derived from bovine sources are a potential source of exposure. It has been demonstrated experimentally that TSEs may result from ocular absorption of protein, and systemic absorption of protein may also occur when cosmetics are applied to lacerated or abraded skin. As a result, it may be concluded that there is some risk of occurrence of vCJD from the use of cattle-derived protein in cosmetics. However, since there are large uncertainties associated with the quantitative estimates of many of the important variables, any quantitative estimate of the risk or rate at which the disease may be expected to occur would be correspondingly imprecise.

The risk of BSE from cosmetics may be reduced through the control of exposure. Aside from the derivation processes used on tallow, the effectiveness of cosmetic manufacturing processes for inactivating BSE prions is unknown. The surest way to prevent transmission of BSE-prion through cosmetics is to avoid the use of high-risk cattle-derived protein in the manufacture of cosmetics.


References

http://www.cfsan.fda.gov/%7Ecomm/bse-ra.html

continued...








January 15th, 2005, 01:56 PM #2
Terry
Registered User


Join Date: Oct 2002
Location: Bacliff, Texas
Posts: 485
-------- Original Message --------
Subject:
Docket No. 2004N-0081 and or RIN number RIN-0910-AF47 Use of Materials Derived
From Cattle in Human Food and Cosmetics [comment submission]
Date: Tue, 13 Jul 2004 16:08:38 -0500
From: "Terry S. Singeltary Sr."
To: [email protected]
CC: [email protected]., [email protected]

COMMENT SUBMISSION
[Docket No. 2004N-O081]
RIN-0910--AF47
Use of Materials Derived From Cattle in Human Food and Cosmetics
http://www.fda.gov/OHRMS/DOCKETS/98...081-nir0001.pdf



http://www.fda.gov/ohrms/dockets/dockets/04n0081/04n0081.htm


2004N-0081 BSE Risk Materials in Foods and Cosmetics

EMC 1 T. Singeltary, Sr. Vol #: 1


http://www.fda.gov/ohrms/dockets/dailys/04/july04/071604/071604.htm



PAUL BROWN



http://www.fda.gov/ohrms/dockets/dockets/04n0081/04N-0081_emc-000005-01.pdf





snip...end...TSS

 

[Econ101]

Flounder, we see a major threat with the bird flu in poultry and BSE in cattle. Is there anything in pork? I am not looking for something, but it really would be a coincidence.

 

[flounder]

for the most part pigs are slaughtered fairly early in life and the incubation time for a TSE to go clinical is not long enough.
however, sub-clinical TSE is very real. with that said, so are TSEs in Pigs;

i posted something somewhere, "7 OF 10 LITTLE PIGGIES WENT ON TO DEVELOP BSE" ;


7 OF 10 LITTLE PIGGIES WENT ON TO DEVELOP BSE;

1: J Comp Pathol. 2000 Feb-Apr; 122(2-3): 131-43. Related Articles,

Links

Click here to read


The neuropathology of experimental bovine spongiform encephalopathy in
the pig.

Ryder SJ, Hawkins SA, Dawson M, Wells GA.

Veterinary Laboratories Agency Weybridge, Woodham Lane, New Haw,
Addlestone, Surrey, KT15 3NB, UK.

In an experimental study of the transmissibility of BSE to the pig,
seven of 10 pigs, infected at 1-2 weeks of age by multiple-route
parenteral inoculation with a homogenate of bovine brain from natural
BSE cases developed lesions typical of spongiform encephalopathy. The
lesions consisted principally of severe neuropil vacuolation affecting
most areas of the brain, but mainly the forebrain. In addition, some
vacuolar change was identified in the rostral colliculi and hypothalamic
areas of normal control pigs. PrP accumulations were detected
immunocytochemically in the brains of BSE-infected animals. PrP
accumulation was sparse in many areas and its density was not obviously
related to the degree of vacuolation. The patterns of PrP
immunolabelling in control pigs differed strikingly from those in the
infected animals.

PMID: 10684682 [PubMed - indexed for MEDLINE]



http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=10684682&dopt=Abstract







-------- Original Message --------
Subject: Re: FW: BSE-L Statement on Texas Cow With Central Nervous
System Symptoms FDA Statement
Date: Wed, 5 May 2004 09:18:41 -0500
From: "Terry S. Singeltary Sr."
Reply-To: B
To: BSE-L
References:



Hello Dr. Gomez,



maybe you could inform the list as to how many TSE test
have been performed on porcine in the USA since the inception of the USA
BSE/TSE surveillance system was put into place some 14 years ago? also,
maybe you would elaborate on the potential for cross contamination from
an event/blunder such as this one in TEXAS? also, what are your views on
the agent in the digestinal track of the pig while being rendered,
regardless whether or not the pig has the disease or not (we could argue
that till the mad cows in the USA are all tested and found), but
normally the pig life span is not long enough to go clinical before
slaughter. I remember the late great Dr. Gibbs comment on this to me,
and he was very much concerned the agent could survive the digestinal
track and could be a concern for rendering. some old observations; The
case for mad pigs in the US From the Consumer Policy Institute and
Consumers Union: March 24, 1997 Stephen F. Sundlof, D.V.M., Ph.D Center
for Veterinary Medicine Food and Drug Administration 7500 Standish
Place, Room 482, HFV1 RockvLIle, MD 20855 Dear Dr. Sundlof: We are
writing to you to submit information that has recently come to our
attention which suggests that a TSElike disease (transmissible
spongiform encephalopathy) might exist in pigs in the U.S. We believe
this new informantion calls for intensive research and makes it urgent
to ban the use of all mammalian proteins, including swine, in the feed
of all food animals, until better answers are found. The evidence for
the potential PSE (porcine spongiform encephalopathy ) is as follows. In
1979, an FSQS veternarian, Dr. Masuo Doi, noticed some unusual central
nervous system (CNS) symptoms in young (about 6 months old) hogs coming
into a slaughter plant In Albany, New York. Since the plant received
hogs from a wide variety of sources (New York, Canada, Indiana,
Illinois, Ohio, and other Midwestern states) and was not a plant used to
dealing with diseased animals, Dr. Doi thought that the problem might be
affecting hogs slaughtered nationwide. So, he decided to conduct a
detailed study on central nervous system (CNS) symptoms/disease in young
hogs coming into that slaughter plant. The study ran for 15 months
(January, 1979 to March, 1980) and consisted of extended observations of
the behavior of animals with suspected CNS symptoms at the plant,
followed by pathological, histopatholpgical, and microbiological work on
tissues from various organs of particular animals after slaughter. For
his behavioral observational work, Dr. Doi extended the usual two day
observation period to three to four days, during which he took careful
notes on the animals' behavior and other vital signs. During the 15
month period of the study, some 106 animals exhibiting CNS symptoms were
retained during antemortem inspection. A 1980 paper that summarized Dr.
Doi's findings on the clinical symptoms and incidence of the 'disease,"
contained descriptions of these symptoms that sound remarkably similar
to the symptoms noted for bovine spongiform encephalopathy (BSE):
"Excitable or nervous temperament to external stimuli such as touch to
the skin, handling and menacing approach to the animals is a common
characteristic sign among swine affected with the disease.... In the
advanced stage of the disease, manifestation of neurological signs are
evidenced in the form of general ataxia . . . Many animals have been
found to be "downers' at first observation; if the hindquarters of these
downers are raised they may be able to walk one or two steps and then
fall to the ground" (Doi et al., 1980: 2, 4). Indeed, a table of
symptoms includes, for the early stage: "excitability and nervousness
(squealing, smacking of lips, grinding of teath, chewing, gnawing ant
foaming at mouth); stiffness of limbs . . . 'tic'; weakness of
hindquarters; focal tremors of skeletal muscles"; and for the advanced
stage: depression; ataxia; crossing over of limbs . . . kneeling posture
. . . crawling". In addition to his clinical observations, Dr. Doi also
made an 8 mm film of thirteen of the affected animals; film of two of
the pigs was shown at the MPI National Pathology Meeting in Seattle,
Washington on flay 20, 1979. Dr. Doi sent tissue samples from suspect
cases to the USDA's Eastern Laboratory in Athens, GA for pathological,
histopathogical and microbiological work. Known infectious diseases were
ruled out. As Dr. Doi points out, "Histopathological studies of tissue
collected from the brain and spinal cord of these animals in the early
stage of the disease show congestion, hemorrhage and neuronal
degeneration. All animals in the advanced stage of the disease have been
confined to have Encephalitis or Meningitis by MPI laboratory" (Doi et
al., 1980: 5). Eventually some 60 animals were confirmed by the MPI
Laboratory to have encephalitis or meningitis, with no ldentifiable
cause. As pointed out in a paper presented at the 1979 MPI National
Pathology Meetings, "Since January, a number of hogs in this
establishment have been found, in antemortem, to show what appears to be
CNS. Sets of tissue samples were sent to the laboratory for examination,
various tests were done which include histological study (EH stain),
fluorescence antibody technique, virus neutralization and viral and
bacteriological isolation. Differential diagnosis was also done to
exclude vitamin B deficiency, post vaccination reaction, chlorinated
hydrocarbon, arthritis, and transport stress" (Doi et al., 1979). The
brains of the 60 animals were examined. The brain of one of these pigs,
on histopathological analysis, exhibited signs reminiscent of a TSE.
This histopathological work was performed by Dr. Karl Langheinrich,
Pathologist-In-Charge at USDA's Eastern Laboratory in Athens, Georgia.
According to the USDA FSQS laboratory report, dated early November,
1979, Dr. Langheinrich noted: "Microscopic examination of the barrow
tissues revealed a encephalopathy and diffuse gliosis characterized by
vacuolated neurons, loss of neurons and gliosis in a confined region
(nucleus) of the brain stem (anterior ventral midbrain). Only an empty
sometimes divided vacuole was present instead of the normal morphology
of a nerve cell. Occasionally a shriveled neuron was seen. According to
. . . Pathology of Domestic Animals, . . . 'The degeneration of neurons,
the reactivity of the glia .... are the classical hallmarks of viral
infection of the central nervous system' .... Scrapie of sheep, and
encephalopathy of mink, according to the literature, all produce focal
vacuolation of the neurons similar to the kind as described for this
pig. I was unable to locate any lead as to the cause of this interesting
phenomenon in other species including swine'' (Langheinrich, 1979).
Indeed, Dr. Langheinrich's main diagnosis was, " Encephalopathy and
diffuse gliosis of undetermined etiology." Portions of the brain were
sent for microbiological testing to a neurologist at the University of
Georgia, where they came up negative for pseudo-rabies. The brain was
unique enough that USDA scientists, such as Dr. Langheinrich and Or.
Dot, mentioned it to student and scientific colleagues over the years.
In 1979-1980, BSE was completely unknown. However, both the behavior of
the pigs, as well as the histopathology on at least one pig, both showed
sign consistent with a porcine TSE. This raises particular concern
became the affected animal was only 6 months old; in an animal this
young, one would rust expect to see any physical signs of TSE in the
brain. Histopathology of TSEs can be very variable, so that spongiform
appearance (i.e. vacuolated neurons) are not always present. Behavioral
changes can be seen in TSE-infected animals before any changes in brain
morphology are visible. Dr. Clarence Gibbs, in testimony before a
Congressional hearing on the TSE issue on January 29, 1997 made just
this point: ''In the mid-1960s, we demonstrated with our French and
English collaborators that during the early incubation of the TSEs, when
the virus titer in the brain was very low, there were already marked
functional changes, even though no pathology was yet detectable, even
ultrastructurally. A month or hero later, polynucleation of neurons
appeared in spider monkeys, incubating kuru, and somewhat later,
microvacuolation and membrane changes visible only by electron
microscopy. This preceded the pest appearance of astrogliosis and
spongiform change. It was only much later that the classical scrapieTSE
pathology appeared with virus titers in brain of 10 -5 or higher"
(Gibbs, 1997; pg. 4). Given that TSEs can cause behavioral changes in
infected animals before any physical changes in the brain can be seen,
that the manifestation of TSE in the brain can be quite variable, and
that changes in brain morphology are not usually seen in 6 month old
animals, we are concerned that the brain of one pig actually showed
physical evidence consistent with a TSE. Following the announcement In
March, 1996 of ten cases of new variant CJD (Creutzfeldt-Jakob Disease)
in the United Kingdom and their possible connection to BSE, Drs. Doi,
Langheinrich and others urged reinvestigation of this case. In August,
1996, the USDA sent five slides, one of which was a histopathology
slide, to Dr. Janice Miller of USDA's Agricultural Research Servicer .
Dr. Miller stained four of the slides for prion protein (she didn't
stain the H&E slide). Dr. Miller told Consumers Union that Dr. Patrick
McCaskey, USDA/FSIS, in charge of the Research Center at Athens, GA,
called her, told her that he had five slides that all showed "problems"
and asked her to stain four of them. The H&E slide, which clearly show
vacuoles in the neurons (one sign of TSE), wasn't stained because to
stain for PrP entails removing the slide cover, baking the slide to
destain it and then restaining it for PrP; they didn't want to risk
destroying the H&E slide. Dr. Doi had kept frozen samples of the brain
and spinal chord of the suspect PSE pig in case the Eastern lab wanted
more material for analysis. Unfortunately, these samples were discarded
when the packing plant in Albany, NY closed in 1991. It appears that the
brain material sent to the Univcrsity of Georgia may have been
discarded. [pers com.. Dr. Doi 3/13/97] Dr. Miller found that the PrP
stained in the four pig slides was found only on the inside of neurons,
while a positive control slide from a scrapie sheep showed massive
amounts of extraneuronal staining. In a letter summarizing her results
(copy attached), she concludes that the PrP stained in this pig was
normal: "In the pig sections you will see a small particulate type of
staining that is confined to neurons and as I indicated on the phone, I
would interpret as normal PrP. It is in marked contrast to the massive
amount of extraneuronal staining seen in the scrapie section" (Miller,
1996). Unfortunately, Dr. Miller's finding toes not conclusively rule
out a TSE. We are concerned that while British BSE and serapie create a
massive amount of extraneuronal staining, there are TSEs where this
isn't the case. Three experiments were done in He U.S. -- in Mission, TX
(APHIS work), Pullman, Washington (ARS work), and Ames, Iowa (ARS work)
-- to see whether sheep scrapie can possibly infect cows. In all the
experiments, cattle were inoculated with tissue from scrapie-infected
sheep primarily by intra-cranial injection, but in the case of the Texas
and Iowa studies also by oral feeding -- to see if cattle were
susceptible to scrapie at all. In all three experiments, the majority of
cows injected in the brain with scrapie-infected sheep material (usually
brains) also developed a fatal spongiform encephalopathy. However, in
all three examples, the symptoms of the spongifonn encephalopathy
differed from "mad cow" disease ~ England, as did the appearances of
slides from their brains. The brain lesions seen in ail these animals
were more variable than those seen in England. When Dr. Miller did
similar staining for PrP from these brains (what she called "bovine
scrapie") she only found PrP stains on the inside of the neurons, not
the massive extraneuronal staining seen in BSE (Miller, pers. comm.,
March 7, 1997). Thus, Dr. Miller's finding of PrP stains only inside the
neurons in the suspect pigs is not particularly reassuring. In November
1996, USDA sent the single histopathology slide to Dr. William Hadlow,
one of the foremost spongiform encephalopathy pathologists in the world.
(For unknown reasons, Dr. Hadlow was only sent the one slide; he was not
told of the existence of the other slides, nor of Dr. Miller's findings,
nor was he told or given the behavioral report from Dr. Doi or the
morphology work by Dr. Langheinrich, or shown film of the affected pigs
[Dr. Hadlow, pers. com., 3/13/97] From this single slide, Dr. Hadlow
found some evidence consistent with TSEs but not enough for a conclusive
diagnosis. He noted that the slide contained vacuoles inside neurons,
one of the signs of a TSE (Dr. Langheinrich had noted this as well).
However, since such vacuoles occasionally occur normally in pigs, he
thought that was not something special: "About twelve (12) neurons in
the parasympathetic nucleus have unilocular optically empty vacuoles in
the perikaryon. This is the site where such vacuolated neurons have been
seen in the swine (as well as in cats and sheep) as an incidental
finding. So I do not think such cells have any significance in this pig"
(Hadlow, 1996). However, he did see evidence, Including changes in
astrocytes, that suggested a TSE, but without examining other parts of
the brain to look for other evidence of TSE, he couldn't be sure: "I am
impressed, though, with what seems to be an increase in the number of
astrocytes in the section. Some astrocytes are in clusters, some are
enlarged and vesicular. Where they are most numerous, a few rod cells
(activated microglia) are seen. These findings suggest some perturbation
of the nervous tissue. Although such a global response occurs in the
transmissible spongifonn encephalopathies, I do no! know its
significance in this case without examining other parts of the brain for
changes characteristic of these diseases. Thus, from looking; at this
one (1) section of brain, I cannot conclude that the pig was affected
with a scrapie-like spongiform encephalopathy" (Hadlow, 1996). In sum,
Dr. Hadlow~s letter does not rule out the possibility of a TSE. He says
that there is suggestive evidence, but that he would need to look at
other slides/sections of the brain, to make a conclusive diagnosis. In
our view, the implications of this data are extremely serious.
Experiments in the United Kingdom have shown that pigs are susceptible
to BSE. Pigs inoculated with BSE develop a TSE (Dawson et a l., 1990).
Feeding experiments are underway in the UK to see if BSE can be orally
transmitted to pigs; as of March, 1997, some 6 years after the start of
the experiment, none of the pigs fed BSE brain have come down with a
TSE. Unfortunately the design of this experiment severely limits what we
will learn from it, and will most likely not tell us conclusively if
pigs can get BSE from feed. It turns out that the pigs were not fed BSE
brain continuously. Rather, the pigs were only fed BSE brain material on
three days, over a three week period (i.e.. one day each week).
Following these three doses, the pigs were never fed contaminated
material again. The total amount of infective material given to the pigs
was therefore quite small. Thus, a negative finding would be hard to
interpret and would not mean that BSE is not orally active in pigs. We
believe that as a top priority USDA should conduct follow-up studies to
look for potential CNS/PSE cases in pigs (we plan to communicate about
this to USDA separately). In brief, we feel that the following kinds of
studies need to be done: i) TSE pathology experts should examine all the
slides from the suspect pig (2709). To our knowledge, at least 12
separate slides exist. ii) Determine if any brain material from the
suspect pig (2709) still exists at the Unlverslty of Georgia. If so,
this material should be retrieved and used for transmission studies. In
particular, suckling pigs should be inoculated with the material and
then permitted to live unto they die of a disease or old age, at which
point their brains should be examined for physical signs of a TSE as
well as for immunchistochemical evidence (i.e. staining looking for the
abnormal PrP). iii) Increase antemortem inspection for CNS symptoms at
hog facilities. Inspectors should be trained to detect the subtle CNS
symptoms seen in the Doi et al. study. At a select number of slaughter
facilities, animals exhibiting CNS symptoms should be removed and held
for observation until they die, at which time their brains should be
examined for evidence of a TSE. iv) Research on CNS symptoms among Me
6,000 or so breeding sows which are permitted to live for 3+ years. Sows
exhibiting CNS symptoms should be removed and held for observation until
they die, at which time then brains should be exernined for evidence of
a TSE. While such work is underway, given the above inforrnabon, we
believe that as a precutionary measure the FDA must expand the proposed
ruminant plus mink-to-ruminnant feed ban to prevent protein from any
material, including hogs, being fed to any food animal. Sincerely,
Michael Hansen, Ph.D Research Associate Jean Halloran Director
References Dawson, M ., Wells, G.A.H., Parker, B.N;J. and A.C Scott.
1990. Primary parental transmission of bovine spongiform encephalopathy
to the pig. Veternary Record, pg. 338. Doi, M., Matzner, N.D. and C.
Rothaug. 1979. Observation of CNS disease in market hogs at Est. 893
Tobin Packing Co., Inc. Albany, New York. United States Department of
Agriculture, Food Safety and Quality.Service, Meat and Poultry
Inspection Service. 7pp. Doi, M, Langheinrich, K. and F. Rellosa. 1980.
Observations of CNS signs in hogs at Est. 893 Tobin Packing C., Inc.
Presented by Dr. Lngheinrich at the MPI National Pathology Meeting in
Seattle, Washington on July 20, 1979. Gibbs, C. 1997. Statement to the
Committee on Governnent Reform and Oversight, Subcommittee on Human
Resources and Intergovernmental Relations, U.S. House of
Representatives. January 29,1997. Hadlow, WJ. 1996. Letter to Patrick
McCaskey, USDA/FSIS/Eastem Lab, dated November 13, 1996. Langheinrich,
KA. 1979. USDA/FSQS Laboratory report on specimen 2709. Dated November
8, 1979 Miller, J. 1996. Letter to Patrick McCaskey, USDA/ESIS/Eastern
Lab, dated September 6, 1996. Dr. Janice Miller , ARS< USDA responds
Mon, 31 Mar 1997 Correspondence My involvement in the "pig incident" (I
refuse to say "mad pig disease" since no such disease has been
recognized): I was asked by Dr. Al Jenny at the National Veterinary
Services Laboratory if I had ever done immunohistochemistry on slides
that had already been stained by hematoxylin and eosin, the standard
stain used for histopathology. I had done it on a few scrapie cases so
he asked if I would do the procedure on some pig brain slides that he
had received from Dr. Pat McCaskey, an FSIS pathologist in Athens, GA.
At the time I didn't know the history of the situation but Dr. Jenny
said I should call Dr. McCaskey and discuss it with him before
proceeding. Only then did I learn a little about the history of the
case. We decided that I wouldn't try to stain all of the slides because
I was afraid the procedure required to remove the cover slips might
damage the sections and Dr. McCaskey was concerned about preserving the
sections for other pathology consultations, if necessary. We agreed that
I would stain 4 of the 5 slides, leaving the slide with the best lesions
untouched. I was also concerned that I didn't know whether the antiserum
we use would stain pig PrP but decided it was worth a try. When I
completed the staining procedure the only positive material I observed
was a small amount of particulate staining within the cell body of some
neurons. We have occasionally observed that kind of staining in brains
from control cattle and sheep in our experiments and interpret it to be
normal PrP. (A similar finding was reported by Dr. Haritani, who first
described the technique for BSE). That observation was reported in our
1994 paper and we stated that consequently we could not interpret
intraneuronal staining as indicative of scrapie (although it may be
present, the bulk of staining is in neuropil, around vessels and
neurons, etc). In that study I think our interpretation was somewhat
validated by the very close correlation we had between
immunohistochemistry and western blot results. At any rate, I told Dr.
McCaskey that my interpretation on the slides was that the only staining
present was consistent with normal PrP. The good news was that the
antiserum did in fact stain something and that it was in the correct
location for normal PrP, indicating that the antiserum would have
detected abnormal PrP, had it been present. Subsequently, I called Dr.
Richard Rubenstein, who provided the antibody we use, and asked if he
knew whether it would react with pig PrP and he said he didn't know.
However, he said it reacted with almost all mammalian species, except
ferret and mink, that he had tried so he would be surprised if it wasn't
reactive with pig PrP. So, having all of this information at hand,
people can decide whether the immunohistochemical test means anything or
not. The lack of a positive control pig tissue (positive sheep tissue is
included in every test) may be viewed by some people as diminishing the
value of a negative result, but feel we did the best we could under the
circumstances. The above recitation describes my experience with the
case in question. I did not photograph the slides and returned all 5 to
Dr. McCaskey. It was later that he had Dr. Hadlow look at the case for
histopathologic interpretation. I did not examine the slides for that
purpose because I do not have experience in scrapie diagnosis and would
not consider my observations meaningful. I appreciated the additional
information about the original study done by Dr. Doi. Although I've
heard bits and pieces of the story from different people, this was the
first time I had heard that 60 of the pigs were diagnosed as having
encephalitis or meningitis. I think that fact, plus the fact that the
pigs were only about 6 months old, should certainly indicate that it's
highly unlikey that a spongiform encephalopathy epidemic was causing the
CNS signs observed. Whether the 1 pig with the questionable
encephalopathy lesions was a TSE could be debated, I suppose. The age
would seem to argue against it and the immunohistochemistry result would
also (at least that's my opinion). We disagree about the implications of
age regarding the liklihood of TSE in a 6-month old pig. Certainly dose
has an effect on incubation period in experimental transmissions and
probably also in the "natural" acquired transmissions. However,
regardless of the manner of transmission, I don't know of any first
passage experimental interspecies transmission where the incubation
period was as short as 6 months. Early onset in mice were achieved only
after adaptation through at least 1 intraspecies transfer. I believe the
same is true for development of the hamster models. With regard to
acquired transmissions, Linda Detwiler's review on scrapie cites
research that indicated infectivity was found in CNS tissues of lambs as
early as 4 months of age: however, they were not showing clinical signs.
>From what I can find in the literature, a clinical case of scrapie under
2 years of age would be exceptional, but with the amount of material
published on that disease I wouldn't want to say it hasn't happened.
With TME the shortest incubation I've seen reported was 9 months.
Elizabeth Williams has indicated that the youngest case of CWD observed
in their wildlife facilities was 18 months old. You stated that in
England calves were getting BSE by one year. In the experimental BSE
transmissions cattle didn't develop clinical signs until the second year
of observation and the earlest sign we observed in cattle inoculated
with sheep scrapie was 14 months. With respect to swine, the only model
we have is the experimental transmission of BSE. The animal first
developed signs about 17 months after inoculation. I think that it would
be highly unlikely for a 6 month old pig to be showing CLINICAL signs of
a TSE (the claim in this particular situation). One can never say never
but it seems reasonable to at least examine what is known and make an
educated estimate about what is likely. A case-control study of CJD.
Dietary risk factors. Am J Epidemiol 122 (3): 443-451 (1985) Davanipour
Z, Alter M, Sobel E, Asher DM, Gajdusek DC The mode of natural
transmission of Creutzfeldt-Jakob disease remains unknown. In a
case-control study conducted in 1981-1983 to evaluate possible dietary
and other sources of the disease, 26 cases were ascertained in the
mid-Atlantic region of the United States, 23 of which were obtained from
accumulated records of the Laboratory of Central Nervous System Studies
of the National Institutes of Health. Controls included 18 family
members and 22 hospital-matched individuals (total sample size, 66). An
increased consumption among patients was found for roast pork, ham, hot
dogs (p less than 0.05), roast lamb, pork chops, smoked pork, and
scrapple (p less than 0.1). An excess consumption of rare meat (p less
than 0.01) and raw oysters/clams (p less than 0.1) was also reported
among the patients. Liver consumption, among organ foods, was greater (p
less than 0.1) among the cases. If Creutzfeldt-Jakob disease is acquired
through ingestion of foods containing the agent, then the food items
identified may be among those which need to be evaluated more
intensively. Larger case-control studies with more focused dietary
questions are warranted. Sundlof can't comment From: Dr. Stephen Sundlof
D.V.M., Ph.D. Director, Center for Veterinary Medicine Food and Drug
Administration : At the present time FDA is in the process of developing
a final rule which will regulate the feeding of certain animal-derived
protein to other animals. In addition to studying the scientific
literature pertaining to TSE's, we have received 700 comments relating
the proposed rule that was published in the Federal Register on January
3, 1977. The information provided by Dr. Hansen and others will be
considered in developing the final rule along with all of the other
information and comments that have been officially submitted to FDA.
Until the final rule is published, FDA is prohibited from commenting on
information that might impact the final rule. Therefore, I am unable to
respond to the documents in Dr. Hansen's letter. I do not have access to
the photomicrographs of the histopathology slides, and I was unaware of
their existance until Dr. Hansen brought the issue to my attention.
Furthermore, I do not have addresses or telephone numbers for Drs. Doi.
Langheinrich, or Hadlow. Someone from the USDA would have this
information but I am not sure who that would be. Webmaster had written:
" Do photomicrographs of any of the 12 slides exist? If you have any of
them, I would like to scan a few of these and post them at high
resolution on the internet so that pathologists world-wide could view
and comment on them. Primary parenteral transmission of bovine
spongiform encephalopathy to the pig. Veterinary Record 1990 127 13 338
Dawson, M.; Wells, G. A. H.; Parker, B. N. J.; Scott, A. C. Ten, weaned
one- to two-week old piglets from a specific pathogen free breeding herd
were inoculated under halothane anaesthesia by simultaneous injections
intracerebrally (0.5 ml) intravenously (1 to 2 ml) and intraperitoneally
(8 to 9 ml) with an inoculum consisting of 10% saline suspension of
pooled homogenised brainstem from 4 natural bovine spongiform
encephalopathy cases. Control piglets were similarly inoculated with
saline. After 69 weeks one challenged pig showed mild aggressive
behaviour towards the animal attendants. Intermittent inappetence and
depression were also noted. Within one week the behavioural changes
included aimless biting activity and there was mild symmetrical ataxia.
The ataxia progressed and 5 weeks after onset of signs the gait ataxia
was generalised with hypermetria and wide-based stance. At this time the
pig was killed. Histopathological examination of the brain revealed
spongiosis of grey matter neuropil with greatest intensity in the medial
geniculate body, superior colliculus and corpus striatum. There was
sparse vacuolation of neuronal perikarya in the dorsal nucleus of the
vagina nerve and widespread astrocytic reaction. Characteristic fibrils
associated with transmissible spongiform encephalopathies were detected
by electron microscopy. One good question is what _pooled_ medical
products do they make from pigs. The key issues for spread of this
disease are the amplification cycle and distribution pooling. That is,
one rotten apple by itself is less of a problem than if it is in a
barrel.



http://www.bseinquiry.gov.uk/files/yb/1990/08/23002001.pdf


http://www.bseinquiry.gov.uk/files/yb/1990/08/23004001.pdf



http://www.bseinquiry.gov.uk/files/yb/1990/08/29003001.pdf



confindential
pigs & pharmaceuticals


http://www.bseinquiry.gov.uk/files/yb/1990/09/10007001.pdf



now what about that mad german red neck ostrich;

Un document de 1991 indiqué dans la liste BSE-L par Terry S. Singeltary A CONTRIBUTION TO THE
NEUROPATHOLOGY OF THE RED-NECKED OSTRICH (STRUTHIO CAMELUS) - SPONGIFORM
ENCEPHALOPATHY



http://www.bseinquiry.gov.uk/files/sc/Seac10/tab06.pdf



I have learned in almost 7 years of studying human/animal TSEs, never say
never, it will bite you in the butt everytime;

> 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".



Suspect Symptoms


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



TSS Gomez, Thomas M. wrote: >######## Bovine Spongiform Encephalopathy ######### >
>All, >Terry provided the results of parenteral inoculation of swine.

snip... end...TSS




-------- Original Message --------
Subject: Re: LONE STAR BEEF WAS INSTRUCTED BY THE USDA TO DISPOSE OF
STUMBLING DOWNER WITHOUT BSE/TSE TEST
Date: Tue, 4 May 2004 21:20:50 -0500
From: "Terry S. Singeltary Sr."
Reply-To: B
To: BSE-L
References:


By Suzanne Gamboa ASSOCIATED PRESS 2:52 p.m. May 4, 2004 WASHINGTON
The byproducts of a Texas cow that was destroyed after it showed
potential signs of a central nervous disorder must be made into pig feed
or be destroyed, the Food and Drug Administration said Tuesday. The FDA
said it tracked down all the material from the cow that was sent to a
processor for rendering into animal feed and other products. All the
material is being held by a business that the agency did not name. The
government has said that none of it got into the human food supply. The
cow was destroyed before it could be tested for mad cow disease, an
incurable illness that eats holes in the brain, attacking the central
nervous system. The FDA planned to send a letter to the business saying
it "will not object to use of this material in swine feed only" because
pigs are not considered susceptible to mad cow disease, one in a family
of illnesses known to infect grass-eating animals. If the business
agrees to only using the material in swine feed, FDA said it will then
track the material through the supply chain from the processor to the
farm to ensure that the feed is monitored and fed only to pigs. The
Agriculture Department learned of the cow Friday. It was taken to
slaughter Wednesday at Lone Star Beef in San Angelo, Texas. Cattle with
mad cow disease exhibit symptoms of a disorder in the central nervous
system. The FDA said inspectors checked the slaughterhouse, the
rendering facility, the farm where the animal came from and the
processor that initially received the cow from the slaughterhouse. On
Monday, Agriculture Department officials said a veterinarian condemned
the animal after seeing it stagger and fall, indicating that it was
either injured or sick with a neurological disorder such as rabies or
mad cow disease. Animals found with those symptoms are supposed to be
kept until the department can collect samples for testing. The
Agriculture Department has said it did not know why that had not happen
in the Texas cow's case. On the Net: www.usda.gov
http://www.signonsandiego.com/news/nation/20040504-1452-cowdeath.html
Greetings, > The FDA planned to send a letter to the business saying it
"will not > object to use of this material in swine feed only" because
pigs are > not considered susceptible to mad cow disease, one in a
family of > illnesses known to infect grass-eating animals. > you got to
be kidding me??? what about cross contamination? what about the
potential for the agent to be in the gut and survive regardless if pig
is exposed, if cow rendered had TSE, no one will ever know will they,
due to the SSS policy which has been in effect since the 80s here in the
USA; 7 OF 10 LITTLE PIGGIES WENT ON TO DEVELOP BSE; 1: J Comp Pathol.
2000 Feb-Apr; 122(2-3): 131-43. ...snip...end...TSS

 

[Econ101]

flounder, how related if any or potentially related is alzheimer's to mad cow disease? From an outsider looking in, there are a lot of similarities.

 

[flounder]

hello ECON101,

you are asking some interesting questions and this one is one of those topics that i try and avoid. you are not trying to get me booted here are you?;-)
this is a no-no. they don't speak about it. they dont try and do very many studies to prove or disprove this. i once wrote some things about it, but then figured if i have as much trouble trying to convice people cjd is cause by TSE/BSE/BASE/Scrapie/CWD etc either directly or indirectly, i would never convince or prove that Alzheimer's is just a low level TSE. so why even go there. just because some 4.5 people a year, with the projected figure in the elderly of the dumb getting dumber, to reach 20 million by 2050. why has caused this? in the past this was not a problem, so why is it now? could Alzheimer's disease be a low level TSE$ only science will tell, but when the corporate interest let the tale be told? have the dieing elderly demented dumb and dumber just become an acceptable way to get rid of the elderly? one does not need to look for for those answers, just look at Katrina and Rita and the dead from just those two storms. mostly elderly. this is progress is it not. dont even get me going there. hell, i watched the dead and elderly floating face down on TV as with most of you and could not for the life of me figure out WHY in Heavens name or HOW could this happen in the USA in 2005, and no one, NO ONE go in to remove those bodies. just left them there to rot, weather was fine and sunny. hell, the year before in a 3rd world country (tsunami), they were picking the dead up the next day. the dead from galveston county here where i live from rita was mostly elderly, if not all, died on the road to hell. well, got off on a wrong foot here, back to TSE and Alzheimer's ;


Regarding Alzheimer's disease

(note the substantial increase on a yearly basis)

http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf

snip...

The pathogenesis of these diseases was compared to Alzheimer's disease at a molecular level...

snip...

http://www.bseinquiry.gov.uk/files/yb/1990/03/12003001.pdf

And NONE of this is relevant to BSE?

There is also the matter whether the spectrum of ''prion disease'' is wider than that recognized at present.

http://www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf

Human BSE

snip...

These are not relevant to any possible human hazard from BSE nor to the much more common dementia, Alzheimers.

snip...

http://www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf

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

From: TSS (216-119-130-123.ipset10.wt.net) Subject: CJD or Alzheimer's, THE PA STUDY...full text Date: May 7, 2001 at 10:24 am PST

Diagnosis of dementia: Clinicopathologic correlations

Francois Boller, MD, PhD; Oscar L. Lopez, MD; and John Moossy, MD

Article abstract--Based on 54 demented patients consecutively autopsied at the University of Pittsburgh, we studied the accuracy of clinicians in predicting the pathologic diagnosis. Thirty-nine patients (72.2%) had Alzheimer's disease, while 15 (27.7%) had other CNS diseases (four multi-infarct dementia; three Creutzfeldt-Jakob disease; two thalamic and subcortical gliosis; three Parkinson's disease; one progressive supranuclear palsy; one Huntington's disease; and one unclassified). Two neurologists independently reviewed the clinical records of each patient without knowledge of the patient's identity or clinical or pathologic diagnoses; each clinician reached a clinical diagnosis based on criteria derived from those of the NINCDS/ADRDA. In 34 (63 %) cases both clinicians were correct, in nine (17%) one was correct, and in 11 (20%) neither was correct. These results show that in patients with a clinical diagnosis of dementia, the etiology cannot be accurately predicted during life.

NEUROLOGY 1989;39:76-79

Several recent papers and reports have addressed the problem of improving the clinician's ability to diagnose dementia. Notable among those reports are the diagnostic criteria for dementia of the American Psychiatric Association, known as DSM III,1 as well as the clinical and neuropathologic criteria for the diagnosis of Alzheimer's disease (AD).2,3 Other researchers have published guidelines for the differentiation of various types of dementia4 and for antemortem predictions about the neuropathologic findings of demented patients.5

Most studies on the accuracy of clinical diagnosis in patients with dementia, especially AD, have used clinicopathologic correlation,6-15 and have found a percentage of accuracy ranging from 43% to 87%. Two recent reports, however,16,17 have claimed an accuracy of 100%. These two reports are based on relatively small series and have consisted of very highly selected patient samples. In our own recent experience, several cases of dementia have yielded unexpected neuropathologic findings,18 and we hypothesized that, in larger series, there would be a significant number of discrepancies between clinical diagnoses and autopsy findings. The present paper reviews the neuropathologic diagnosis of 54 demented patients who were autopsied consecutively at the University of Pittsburgh over a 7-year period, and reports the ability of clinicians to predict autopsy findings.

Material and methods. We independently reviewed the pathologic data and clinical records of 54 consecutive patients who had had an autopsy at the University of Pittsburgh (Presbyterian University Hospital [PUH] and the Pittsburgh (University Drive) Veterans Administration Medical Center [VAMC]), between 1980 and 1987.

The 54 cases included all those where dementia was diagnosed clinically but for which an obvious etiology, such as neoplasm, trauma, major vascular lesions, or clinically evident infection had not been found. The brains, evaluated by the Division of Neuropathology of the University of Pittsburgh, were obtained from patients cared for in different settings at their time of death.

On the basis of the amount of information available in each case, we divided the patients into three groups. Group 1 included 12 subjects who had been followed for a minimum of 1 year by the Alzheimer Disease Research Center (ADRC) of the University of Pittsburgh. ADRC evaluations include several visits and neurologic and neuropsychological testing as well as repeated laboratory tests, EEG, and CT.19,20

Group 2 included 28 patients who had been seen in the Neurology Service of PUH, of the VAMC, or in geriatric or psychiatric facilities of the University of Pittsburgh or at Western Psychiatric Institute and Clinic. All patients were personally evaluated by a neurologist and received a work-up to elucidate the etiology of their dementia.

Group 3 included 14 patients seen in other institutions; in most cases, they had also been seen by a neurologist and had had laboratory studies that included CT of the head. In three of the 14 cases, however, the information could be gathered only from the clinical summary found in the autopsy records.

Many of these subjects were referred for autopsy to the ADRC because of a public education campaign that encourages families to seek an autopsy for their relatives with dementia.

Pathologic data. All brains were removed by a neuropathologist as the first procedure of the autopsy at postmortem intervals of between 4 and 12 hours. The unfixed brain was weighed and the brainstem and cerebellum were separated by intercollicular section. The cerebral hemispheres were sectioned at 1-cm intervals and placed on a glass surface cooled by ice to prevent adhesion of the tissue to the cutting surface. The brainstem and cerebellum were sectioned in the transverse plane at 6-mm intervals. Brain sections were fixed in 10% buffered formalin. Selected tissue blocks for light microscopy were obtained from sections corresponding as exactly as possible to a set of predetermined areas used for processing brains for the ADRC protocol; additional details of the neuropathologic protocol have been previously published.18,21 Following standard tissue processing and paraffin embedding, 8-um-thick sections stained with hematoxylin and eosin and with the Bielschowsky ammoniacal silver nitrate impregnation were evaluted. Additional stains were used when indicated by the survey stains, including the Bielschowsky silver technique as previously reported.21

Clinical data. The medical history, as well as the results of examinations and laboratory tests, were obtained from the medical records libraries of the institutions where the patient had been followed and had died. We supplemented these data, when appropriate, with a personal or telephone interview with the relatives.

One neurologist (O.L.L.) recorded the information to be evaluated on two forms. The first form included sex, age, handedness, age at onset, age at death, course and duration of the disease, education, family history, EEG, CT, NMR, medical history, and physical examination as well as examination of blood and CSF for factors that could affect memory and other cognitive functions. The form also listed the results of neuropsychological assessment, and the characteristics and course of psychiatric and neurologic symptoms. The form provided details on the presence, nature, and course of cognitive deficits and neurologic signs. The second form was a 26-item checklist derived from the NINCDS-ADRDA Work Group Criteria for probable Alzheimer's disease.2 The forms did not include the patient's identity, the institution where they had been evaluated, the clinical diagnosis, or the pathologic findings.

Each form was reviewed independently by two other neurologists (F.B. and J.M.), who were asked to provide a clinical diagnosis. In cases of probable or possible AD, the two neurologists followed the diagnostic criteria of the NINCDS/ ADRDA work group.2

The results were tabulated on a summary sheet filled out after the two neurologists had provided their diagnosis on each case. The sheet included the diagnosis reached by the two neurologists and the diagnosis resulting from the autopsy.

Table 1. Pathologic diagnosis in 54 patients with dementia

N %

Alzheimer's disease alone 34 62.9

Alzheimer's disease and 2 3.7 Parkinsons's disease

Alzheimer's disease with 2 3.7 multi-infarct dementia

Alzheimer's disease with amyotrophic lateral sclerosis 39 72.2

Total Alzheimers disease 39 72.2

Multi-infarct dementia 4 7.4

Multi-infarct dementa 1 1.8 with Parkinson's disease

Parkinson's disease 2 3.7

Progressive subcortical gliosis 2 3.7

Creutzfeldt-Jakob disease 3 5.5

Progressive supranuclear palsy 1 1.8

Huntington's disease 1 1.8

Unclassified 1 1.8

Total other disease 15 27.7

Total all cases 54

Table 2. Clinical diagnosis

Clinical diagnosis Clinician #1 --- #2

Probable AD 29 21

Probable AD and MID 3 0

Probable AD and thyroid disease 1 2

Probable AD and PD 3 1

Probable AD and ALS 1 0

Probable AD and 0 1 olivopontocerebellar degeneration

Total probable AD 37 25 (68.5%) (46.2%)

Possible AD 3 2

Possible AD and MID 2 2

Possible AD and alcoholism 0 1

Possible AD and depression 1 0

Possible and thyroid disease 0 3

Possible AD and traumatic 1 2 encephalopathy

Possible AD and PD 3 6

Total Possible AD 10 16 (18.5%) (29.6%)

Atypical AD 0 1

Atuypical AD and MID 0 1

MID 2 4

MID and PD 3 0

Dementia syndrome of depression 0 1

HD 1 1

Wernicke-Korsakoff syndrome 1 0

Dementia of unknown etiology 0 5

Total 54 54

Results. The subjects included 26 women and 28 men who ranged in age from 30 to 91 years (mean, 72.2; SD, 10.7).

Autopsy findings. Table 1 shows that 39 (72.2%) of the 54 cases fulfilled histologic criteria for AD, with or without other histopathologic findings. The remaining 15 cases (27.7%) showed changes corresponding to other neurodegenerative disorders, cerebrovascular disease, or Creutzfeldt-Jakob disease (CJD). Seven cases met the histopathologic criteria for multi-infarct de-mentia (MID). Five cases (9.2%) showed changes associated with Parkinson's disease (PD).

Twenty-two of the 39 AD patients (56%) were age 65 or greater at the time of the onset of the disease. Seven of the 15 patients in the group with other diseases (47%) were age 65 or older at the time of disease onset.

Clinical diagnosis. There was a general adherence to the criteria specified by McKhann et al.2 However, the two clinicians in this study considered the diagnosis of probable AD when the probability of AD was strong even if a patient had another disease potentially associated with dementia that might or might not have made some contribution to the patient's clinical state (table 2).

Accuracy of the clinical diagnosis (table 3). Group 1 (N = 12). There were six men and six women. Ten cases (83.3%) met the histologic criteria for AD. In nine cases (75.0%), the diagnosis of both clinicians agreed with the pathologic findings; in the other case (8.3%), one clinical diagnosis agreed with the histologic findings. The remaining two cases (16.6%) had histopathologic diagnoses of CJD and progressive supranuclear palsy (PSP), respectively. Both cases were incorrectly diagnosed by both clinicians.

Group 2 (N = 28). There were 11 women and 17 men. Eighteen cases (64.2%) had the histopathologic features for AD with or without additional findings. Sixteen of these cases (57.1%) were correctly diagnosed by both clinicians, one case by one of them, and both incorrectly diagnosed one case. The remaining ten cases (35.7%) included two with CJD; two with subcortical gliosis (SG); two with PD, one of which was associated with MID; one case of Huntington's disease (HD); two cases with MID; and one unclassifed. Only one, the HD case (3.5%), was correctly diagnosed by both observers, and four cases (14.2%), two MID and two PD, one associated with MID, were correctly diagnosed by one clinician.

Group 3 (N = 14). In this group there were nine women and five men. Eleven cases (78.5%) met the histopathologic criteria for AD with or without additional findings. Eight of these cases (57.1%) were correctly diagnosed by both clinicians, two cases by one of them, while both were incorrect in one case. Of the remaining three cases (21.4%), only one was correctly diagnosed (7.1%) by one clinician. Both missed the two other cases of MID.

There was no statistically significant difference in diagnostic agreement across patient groups in which the amount of clinical information was different (X2 = 1.19; p > 0.05).

Table 3. Accuracy of the clinical diagnosis by two clinicians

Both One Neither Correct Correct Correct

Group 1 (N = 12) 9 1 2(16.6%)

Group 2 (N = 28) 17 5 6(21.4%)

Group 3 (N = 14) 8 3 3(21.4%)

Table 4. Previously reported studies of clinicopathologic correlation in demented patients*

Agreement %

Number of cases AD

Retrospective studies

Todorov et al, 1975(7) 776 43

Perl et al, 1984(9) 26 81

Wade et al, 1987(12) 65 85

Alafuzoff et al, 1987(13) 55 63

Kokmen at al, 1987(14) 32 72

Joachim et al, 1987(15) 150 87

Prospective studies

Sulkava et al, 1983(8) 27 82

Molsa et al, 1985(10) 58 71

Neary et al, 1986(11) 24 75

Martin et al, 1987(16) 11 100

Morris et al, 1987(17) 25 100

* Certain differences in methodology need clarification. Some authors7,8,10,11,12,13,16,17 tabulated patients with AD alone, and others9,14,15 included patients with AD plus other diseases, eg, Parkinson's disease and MID. We have combined AD alone and AD plus MID and other neurodegenerative diseases.

Discussion. Our results indicate that in a population of patients with dementias of varied etiology, the diagnosis could be correctly inferred by at least one of two clinicians in approximately 80% of cases. For one observer, the sensitivity of clinical diagnosis for AD was 85% and the specificity was 13%, and for the other, it was 95% and 33% respectively.

In the cases with a discrepancy between the clinical diagnosis and the neuropathologic findings, the great majority of patients had atypical clinical courses and findings. The three cases with autopsy findings of CJD had a much longer course than is usually seen with that condition and failed to show the usual EEG abnormalities. The patient with autopsy findings of PSP did not show the disorder in the extraocular movements usually associated with that condition. An atypical course was also present for two AD cases and two MID cases that did not have any feature suggestive of vascular disease. In one MID case, the CT did not show any focal lesions, while in the other it was not available. With regard to the two patients with SG, the pathologic diagnosis is so unusual and so infrequently recorded that clear clinical correlates are not evident.18 The third category of possible error is the patient listed as unclassified, for whom no specific neuropathologic diagnosis could be reached.22

The small number of neuropathologic diagnoses of Parkinson's disease reflects that, for the purpose of this series, the diagnosis of PD was made only when there were both a clear-cut clinical history and the neuropathologic findings characteristic of the disease, such as Lewy bodies, neuronal loss, globose neurofibrillary tangles, astrocytosis, and extraneuronal melanin pigment in substantia nigra and locus ceruleus.

Are these results derived from a sample of 54 patients representative of disease patterns in the community? Generally, the diagnosis of patients reported from major medical centers tend to be biased since the more complicated cases are referred there. In this study, however, this bias may be less important. Due to the major public education campaign about dementia and AD sponsored by the ADRC, there is a widespread awareness in Pittsburgh and in the surrounding regions of Western Pennsylvania of the value of an autopsy for a definitive diagnosis. Therefore, the great majority of cases were referred to us because the family wanted to know the precise etiology of a case of dementia.

The significant improvement in the clinical diagnosis of AD is a recent phenomenon. Due to the publicity and the advances in communication of scientific investigations, most physicians are more likely to consider AD as the main cause of dementia. The current risk of overdiagnosing AD reminds one of what occurred during the 1960s with the diagnosis of "atherosclerotic dementia."6 The high sensitivity and low specificity for AD shown in our study may reflect that possibility.

Because of the varying criteria for "other dementias" in many publications, we chose to analyze the accuracy of clinical diagnosis in terms of the diagnosis of AD alone or AD plus other neuropathologic findings. Several retrospective studies have attempted to point out reliable clinical and pathologic features for diagnosing the dementias, especially AD. The study of Tomlinson et al6 is not included in table 4 because there was no attempt to validate the clinical diagnosis with pathologic findings. The reports surveyed vary considerably in size and methodology. Sample size, for example, ranges from 26 subjects9 to 776 subjects.7 Some studies base the diagnosis on limited clinical information,7'9'14'15 others use widely accepted diagnostic criteria such as those specified in DSM III,13 and one group uses a standardized clinical assessment of patients enrolled in a longitudinal study.12 The reported accuracy of the clinical diagnosis of AD ranges from 43%7 to 87%.15

Recent prospective studies that adhere to strict clinical criteria,10'11'17 those in DSM III8 or those proposed by McKhann et al,16 indicate improved accuracy of clinical diagnosis of the most common causes of dementia, especially AD. In sample sizes ranging from 11 subjects16 to 58 subjects,l0 the accuracy of clinical diagnosis is reported as ranging from 71%10 to 100%16'17' Only two series, both based on small samples, report a 100% accuracy. We consider it unlikely that such accuracy could be confirmed in large series because of some inevitable imprecision in clinical diagnoses and the variability of clinical pictures. Furthermore, although researchers generally agree on the application of uniform criteria in clinical diagnosis of dementia, opinions still differ about specific diagnostic criteria, as well as about the pathologic characterization of dementia. Except for those small series, the results summarized in table 4(7-15) is are remarkably consistent with ours.

In table 3, although there was no statistical difference (p > 0.05) in diagnostic agreement across patient groups, there is a trend toward a lower percentage of diagnostic errors for the patients who had been followed most intensely (16% in group 1 compared with 21% in groups 2 and 3). The difference is not great, and it is, in fact, surprising to find out that in the patients about whom relatively little was known (group 3) the percentage of diagnostic error was the same as among patients seen by neurologists and for whom much more data were available (group 2). These paradoxical findings probably indicate that both clinicians learned to extract essential diagnostic criteria2 in spite of the variations in the amount of information available for consideration. It may well be that clinical, radiographic, and laboratory assessment of patients with dementia is burdened with information that is excessive and unessential for purely diagnostic purposes.

Acknowledgments

We thank Dr. A. Julio Martinez and Dr. Gutti Rao from the Division of Neuropathology for autopsy data. Mrs. Margaret Forbes, Ms. Annette Grechen, and Mrs. Paula Gent helped in the preparation of the manuscript.

References

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Organic Dementia Disorders, 3rd ed. Washington DC, APA, 1983:101-161.

2. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan E. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Dis-ease. Neurology 1984;34:939-944.

3. Khachaturian Z. Diagnosis of Alzheimer's disease. Arch Neurol 1985;42:1097-1105.

4. Cummings J, Benson F. Dementia: a clinical approach, 1st ed. Boston: Butterworths, 1983.

5. Rosen WG, Terry R, Fuld P, Katzman R, Peck A. Pathological verification of ischemic score in differentiation of dementias. Ann Neurol 1980;7:486-488.

6. Tomlinson BE, Blessed G, Roth M. Observations on the brains of demented old people. J Neurol Sci 1970;11.205-242.

7. Todorov A, Go R, Constantinidis J, Elston R. Specificity of the clinical diagnosis of dementia. J Neurol Sci 1975;26:81-98.

8. Sulkava R, Haltia M, Paetau A, Wikstrom J, Palo J. Accuracy of clinical diagnosis in primary degenerative dementia: correlation with neuropathological findings. J Neurol Neurosurg Psychiatry 1983;46:9-13.

9. Perl D, Pendlebury W, Bird E. Detailed neuropathologic evalua-tion of banked brain specimens submitted with clinical diagnosis of Alzheimer's disease. In: Wirtman R, Corkin S, Growdon J, eds. Alzheimer's disease: advances in basic research and therapies. Proceedings of the Fourth Meeting of International Study Group on the Treatment of Memory Disorders Associated with Aging. Zurich, January 1984. Cambridge, MA: CBSM, 1984:463. Molsa PK, Paljarvi L, Rinne JO, Rinne UK, Sako E. Validity of clinical diagnosis in dementia: a prospective clinicopathological study. J Neurol Neurosurg Psychiatry 1985;48:1085-1090.

11. Neary D, Snowden JS, Bowen D, et al. Neuropsychological syn-dromes in presenile dementia due to cerebral atrophy. J Neurol Neurosurg Psychiatry 1986;49:163-174.

12. Wade J, Mirsen T, Hachinski V, Fismm~ M, Lau C, Merskey H. The clinical diagnosis of Alzheimer disease. Arch Neurol 1987;44:24-29.

13. Alafuzoff I, Igbal K, Friden H, Adolfsson R, Winblad B. Histopathological criteria for progressive dementia disorders: clinicalpathological correlation and classification by multivariate data analysis. Acta Neuropathol (Berl) 1987,74:209-225.

14. Kokmen E, Offord K, Okazaki H. A clinical and autopsy study of dementia in Olmsted County, Minnesota, 1980-1981. Neurology 1987;37:426-430.

15. Joachim CL, Morris JH, Selkoe D. Clinically diagnosed Alzheimer's disease: autopsy neuropathological results in 150 cases. Ann Neurol 1988;24:50-56.

16. Martin EM, Wilson RS, Penn RD, Fox JH, Clasen RA, Savoy SM. Cortical biopsy results in Alzheimer's disease: correlation with cognitive deficits. Neurology 1987;37:1201-1204.

17. Morris JC, Berg L, Fulling K, Torack RM, McKeel DW. Validation of clinical diagnostic criteria in senile dementia of the Alzheimer type. Ann Neurol 1987;22:122.

18. Moossy J, Martinaz J, Hanin I, Rao G, Yonas H, Boiler F. Thalamic and subcortical gliosis with dementia. Arch Neurol 1987;44:510-513.

19. Huff J, Becker J, Belle S, Nebes R, Holland A, Boller F. Cognitive deficits and clinical diagnosis of Alzheimer's disease. Neurology 1987;37:1119-1124.

20. Huff J, Boiler F, Lucchelli F, Querriera R, Beyer J, Belle S. The neurological examination in patients with probable Alzheimer's disease. Arch Neurol 1987;44:929-932.

21. Moossy J, Zubenko G, Martinez AJ, Rao G. Bilateral symmetry of morphologic lesions in Alzheimer's disease. Arch Neurol 1988;45:251-254.

22. Heilig CW, Knopman DS, Mastri AR, Frey W II. Dementia without Alzheimer pathology. Neurology 1985;35:762-765.

From the Departments of Neurology (Drs. Boller, Lopez, and Moossy), Psychiatry (Dr. Boller), Pittsburgh (University Drive) Veterans Administration Medical Center (Dr. Boller), Department of Pathology (Division of Neuropathology) (Dr. Moossy), and the Pittsburgh Alzheimer Disease Research Center (Drs. Boller, Lopez, and Moossy), University of Pittsburgh Medical School, Pittsburgh, PA.

Supported in part by NIH Grants nos. AG05133 and AG03705, NIMH Grant no. MH30915, by funds from the Veterans Admin., and by the Pathology Education and Research Foundation (PERF) of the Department of Pathology, University of Pittsburgh.

Presented in part at the fortieth annual meeting of the American Academy of Neurology, Cincinnati. OH, April 1988.

Received April 7, 1988. Accepted for publication in final form July 20, 1988.

Address correspondence and reprint requests to Dr. Boller, Department of Neurology, 322 Scaife Hall, University of Pittsburgh Medical School, Pittsburgh, PA 15261.

January 1989 NEUROLOGY 39 79

TSS

http://www.vegsource.com/talk/lyman/messages/9249.html

From: TSS (216-119-130-151.ipset10.wt.net) Subject: Evaluation of Cerebral Biopsies for the Diagnosis of Dementia Date: May 8, 2001 at 6:27 pm PST

Subject: Evaluation of Cerebral Biopsies for the Diagnosis of Dementia Date: Tue, 8 May 2001 21:09:43 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: [email protected]


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

Evaluation of Cerebral Biopsies for the Diagnosis of Dementia

Christine M. Hulette, MD; Nancy L. Earl, Md; Barbara J. Crain, MD, Phd

· To identify those patients most likely to benefit from a cerebral biopsy to diagnose dementia, we reviewed a series of 14 unselected biopsies performed during a 9-year period (1980 through 1989) at Duke University Medical Center, Durham, NC. Pathognomonic features allowed a definitive diagnosis in seven specimens. Nondiagnostic abnormalities but not diagnostic neuropathologic changes were seen in five additional specimens, and two specimens were normal. Creutzfeldt-Jakob disease was the most frequent diagnosis. One patient each was diagnosed as having Alzheimer's disease, diffuse Lewy body disease, adult-onset Niemann-Pick disease, and anaplastic astrocytoma. We conclude that a substantial proportion of patients presenting clinically with atypical dementia are likely to receive a definitive diagnosis from a cerebral biopsy. However, in those with coexisting hemiparesis, chorea, athetosis, or lower motor neuron signs, cerebral biopsies are less likely to be diagnostic. (Arch Neurol. 1992;49:28-31)

"Dementia" is a syndrome characterized by global deterioration of cognitive abilities and is the general term used to describe the symptom complex of intellectual deterioration in the adult. It is associated with multiple causes, although Alzheimer's disease (AD) alone accounts for approximately 60% of cases.1-3

Interest in the accuracy of the diagnosis of dementia is a relatively recent phenomenon, reflecting both an increase in physicians' awareness of multiple specific causes of dementia and a marked increase in both the incidence and prevalence of dementia associated with the increase in the elderly population.4' The clinical evaluation remains the key to the differential diagnosis, and in most cases dementia can be diagnosed accurately by clinical criteria. However, the definitive diagnoses of AD.1'5'7 Pick's disease,8'10 Creutzfeldt-Jakob disease (CJD),11-16 Binswanger's disease,17'18' and diffuse Lewy body disease19-22 still require histologic examination of the cortex to identify characteristic structural changes.

Brain tissue is almost invariably obtained at autopsy, and the vast majority of pathologic diagnoses are thus made post mortem. Alternatively, an antemortem histologic diagnosis can be provided to the patient and his or her family if a cerebral biopsy is performed while the patient is still alive. Because brain biopsies for dementia are not routinely performed, we sought to define the spectrum of pathologic changes seen in a retrospective unselected series of adult patients undergoing cerebral biopsy for the diagnosis of atypical dementing illnesses and to determine the patient selection criteria most likely to result in a definitive diagnosis.

MATERIALS AND METHODS

Cerebral biopsies performed solely for the diagnosis of dementia in adult patients were identified by a manual search of the patient files of the Division of Neuropathology, Duke University Medical Center Durham, NC, and by a computerized search of discharge diagnoses of patients undergoing brain biopsies. Fourteen cases were identified from the period 1980 to 1989. Patients undergoing biopsies for suspected tumor, inflammation, or demyelinating disease were excluded. A clinical history of dementia was an absolute requirement for inclusion in the study. Diagnosis was based on Dignostic and Statistical Manual of Mental Disorders, Third Edition, and on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (ADRDA) criteria for probable AD.23

The published recommendations for handling tissue from patients with suspected CJD were followed in every case.24-26 Briefly, tissue was transported in double containers clearly marked "Infectious Disease Precations." Double gloves, aprons, and goggles were used at all times. Tissue was fixed in saturated phenol in 3.7% phosphate-buffered formaldehyde for 48 hours25 and subsequently hand processed for paraffin embedding. At least 1 cm(to 3 power) of tissue was available for examination from each patient, except for patient 7, who underwent bilateral temporal lobe needle biopsies. Patient 14 underwent biopsy of both frontal and temporal lobes.

One paraffin block was prepared for each biopsy specimen, and sections were routinely stained with hematoxylin-eosin, luxol fast blue, Congo red, alcian blue, periodic acidSchiff, and modified King's silver stain27 in every ease, except for case 7, in which the diagnosis was made by frozen section. Portions of both gray and white matter were primarily fixed in glutaraldehyde and embedded in epoxy resin (Epon). Tissue was examined by electron microscopy if abnormalities, such as neuronal storage or other inclusions, were seen in routine paraffin sections.

Khachaturian's5 National Institute of Neurological and Communicative Disorderers and Stroke/ADRDA criteria for quantitation of senile plaques and the diagnosis of AD were used in all cases after 1985. At the time of our, study, these criteria were also applied retrospectively to cases accessioned before 1985. No attempt was made to grade the severity of other abnormalities (eg, gliosis and spongiform change), and the original pathologic diagnoses were not revised.

RESULTS

The clinical presentations, biopsy findings, and follow-up data, including postoperative complications, are summarized in Table 1 for all 14 patients. Their biopsy findings are summarized in Table 2.

The ages of this unselected group of 14 patients who underwent cerebral biopsies for dementia ranged from 32 to 78 years (mean, 51.6 years). There were seven men and seven women. Duration of symptoms ranged from 1 month to 6 years (mean, 2.3 years). No differences were noted between the group with diagnostic biopsies (cases 1 through 7) and the group with nondiagnostic biopsies (cases 8 through 14) with regard to age at the time of biopsy or duration of symptoms. However, five of seven patients in the nondiagnostic group had hemiparesis, chorea, athetosis, or lower motor neuron signs. None of these findings was present in the patients with diagnostic biopsies. Visual disturbances, abnormal eye movements, and ataxia were present in four of seven cases with diagnostic biopsies but were absent in the group with nondiagnostic biopsies.

In this series of 14 patients, two experienced postoperative complications, one of which was severe. Patient 2 developed an intraparenchymal parietal cortex hemorrhage and was mute after biopsy. Patient 9 developed a subdural hygroma that was treated uneventfully.

Eight patients died 1 month to 9 years after biopsy. An autopsy was performed in five of these eight patients. One of these patients (patient 4) had a firm diagnosis of presenile AD on biopsy, which was confirmed at autopsy. Patient 3 had a biopsy diagnosis of CJD, which was also confirmed at autopsy. Two patients with only white-matter gliosis diagnosed at biopsy had autopsy diagnoses of amyotrophic lateral sclerosis with dementia (patient 8) and CJD (patient 9). One patient in whom a biopsy specimen appeared to be normal had Huntington disease identified at autopsy (patient 14). At the time of this writing, four patients are still alive, two are in clinically stable condition 1 to 2 years after biopsy, and two are severely demented 2 to 3 years after biopsy. Two patients (one with a definite and one with a possible diagnosis of CJD) have been unavailable for follow-up.

COMMENT Our study of patients presenting with atypical dementia reaffirms the diagnostic utility of cerebral biopsy. In selected cases, cerebral biopsy results in a high yield of definitive diagnostic information. A wide variety of disorders may be encountered, including CJD, AD, diffuse Lewy body disease, and storage disorders, such as Niemann-Pick disease.28-30 The diagnosis of Niemann-Pick disease type C was confirmed by assay of cholesterol esterification in cultured fibroblasts31'32' with markedly abnormal results in one patient, who was described in detail elsewhere.33

One example of an unsuspected anaplastic astrocytoma (case 7) was also encountered. This case was unusual in light of currently used sensitive imaging techniques. This patient may have been suffering from gliomatosis cerebri.

Table 1.--Summary of Clinical Presentation and Course*

Case/Age,y/Sex

Duration of Symptoms, y

Clincial Findings

Biopsy

Follow-up ==========

1/60/F

0.1

Dementia, left-sided homonymous hemianopia, myoclonus, EEG showing bilateral synchronous discharges

CJD

Unavailable ==========

2/57/M

0.4

Dementia, aphasia, myoclonus; visual disturbance; facial asymmetry, abnormal EEG

CJD

Postoperative intraparenchymal hemorrhage, mute dead at 58 y, no autopsy ==========

3/59/M

2

Dementia, apraxia, visual disturbance, bradykinesia, EEG showing periodic sharp waves

CJD

Dead at 61 y, autopsy showed CJD =========

4/32/M

1

Dementia, myclonus, ataxia, family history of early-onset dementia

AD

Dead at 40 y, autopsy showed AD =========

5/78/M

6

Dementia, paranoia, agitation, rigidity

Diffuse Lewy body disease

Dead at 78 y, no autopsy =========

6/37/F

6

Dementia, dysarthria, abnormal eye movements, ataxia

Neuronal storage disorder, adultonset N-P type II

Stable at 39 y =========

7/58/F

0.3

Dementia, amnesia, depression, partial complex seizures

Anaplastic astrocytoma

Dead at 58 y, no autopsy ==========

8/37/M

2

Dementia, dysarthria, upper-extremity atrophy and fasciculations

Gliosis

Dead at 38 y, auotpsy showed amyotrophic lateral sclerosis with white-matter gliosis =========

9/45/F

2

Dementia, aphasia, right-sided hemiparesis, rigidity, athetosis

Gliosis

Postoperative subdural hygroma, dead at 50 y, autopsy showed focal CJD =========

10/56/F

2

Dementia, myoclonus, cerebellar dysaarthria, EEG showing biphasic periodic sharp waves

Consistent with CJD

Unavailable ==========

11/60/F

2

Dementia, dysarthria, right-sided hemiparesis, hypertension, magnetic resonance image showing small vessel disease

Plaques, gliosis

stable at 61 y =========

12/52/F

2

Dementia, aphasia, right-sided hemiparesis

Gliosis

Bedridden, severely demented at 54 y =========

13/40/M

0.5

Dementia, mild bifacial weakness, concrete thinking, altered speech

Normal

Stable at 41 y =========

14/52/M

6

Dementia, choreoathetosis, family history of senile dementia, computed tomographic scan showing normal caudate

Normal

Dead at 61y, autopsy showed Huntington's disease, grade II/IV ========== * EEG indicates electroencephalogram; CJD, Creutzfeldt-Jakob disease; AD, Alzheimer's disease; and N-P, Niemann-Pick disease.

Table 2.--Pathologic Findings at Biopsy *

Case Site of Biopsy Type of Biopsy Tissue Examined Spongiform Change Neuritic Plaques per X 10 Field Tangles White Matter Gliosis Other

1 R temporal Open 1 cm3 + 0 0 0 0 =====

2 L temporal Open 1 cm3 + 0 0 0 0 =====

3 R temporal Open 1 cm3 + 0 0 0 0 =====

4 R frontal Open 1 cm3 0 >100 + + Amyloid angiopathy =====

5 R temporal Open 1 cm3 0 9 0 0 Lewy bodies =====

6 R temporal Open 1 cm3 0 0 0 0 Neuronal storage =====

7 R temporal/L temporal Needle/needle 1 X 0.3 X 0.3 cm / 1 X 0.3 X 0.1 cm 0/0 0/0 0/0 +/0 0/anaplastic astrocytoma =====

8 R frontal Open 1 cm3 o o o + 0 =====

9 L parietal Open 1 cm3 0 0 ± + 0 =====

10 R temporal Open 1 cm3 ± 0 0 0 0 =====

11 L temporal Open 1 cm3 0 23 0 + 0 =====

12 L temporal Open 1 cm3 0 0 0 + 0 =====

13 r frontal Open 1 cm3 0 0 0 0 0 =====

14 L temporal/L frontal Open/open 1 cm3/ 1 cm3 0/0 0/0 0/0 0/0 0/0 ===== * Plus sign indicates present; zero, absent; and plus/minus sign, questionably present

Positron emission tomography showed multiple areas of increased uptake, even though the magnetic resonance image was nondiagnostic and showed only subtle increased signal intensity on review. Bilateral temporal lobe needle biopsies yielded abnormal findings. Biopsy of the right side showed only reactive gliosis, which may have been adjacent to tumor. Biopsy of the left side, performed 3 days later, was diagnostic for anaplastic astrocytoma. Unfortunately, permission for an autopsy was refused, and complete evaluation of the underlying pathologic process thus must remain speculative.

The high incidence of definite and probable CJD in our series indicates that it is imperative that appropriate precautions are taken to prevent the transmission 0f disease to health care workers when biopsy tissue from patients with dementia is handled.24-26

At our institution, cerebral biopsy for the diagnosis of dementia is reserved for patients with an unusual clinical course or symptoms that cannot be diagnosed with sufficient certainty by other means. In most instances, cerebral biopsy is unnecessary and is clearly not a procedure to be proposed for routine diagnostic evaluation. In all cases, extensive clinical, metabolic, neuropsychological and radiologic evaluations must be performed before cerebral biopsy is considered. In addition, preoperative consultations among neurologists, neurosurgeons, neuroradiologists, and neuropathologists are necessary to ascertain the optimal biopsy site given the clinical data to ensure that maximal infornmtion is derived from the biopsy tissue.

An optimal biopsy specimen is one that is taken from an affected area, handled to eliminate artifact, and large enough to include both gray and white matter.34 Open biopsy is generally preferred because it is performed under direct visualization and does not distort the architecture of the cerebral cortex. This method also provides sufficient tissue (approximately 1 cm3) to perform the required histologic procedures.

Some physicians question the utility of diagnostic cerebral biopsies in dementia, stating that the procedure is unlikely to help the patient. While it is frequently true that the diagnoses made are untreatable with currently available therapeutic modalities, this is by no means universally true. Kaufman and Catalano35 noted that cerebral biopsy has revealed specific treatable illnesses, such as meningoencephalitis and multiple sclerosis. Our patient with anaplastic astrocytoma (patient 7) underwent radiation therapy, although she quickly died of her disease. Furthermore, when a definitive diagnosis can be made, even of incurable illnesses, such as CJD and AD, it is often possible to give an informed prognosis to the family and to help them plan for the future.

The formulation of indications, for diagnostic cerebral biopsy raises difficult and complex issues. In 1986, Blemond36 addressed the clinical indications and the legal and moral aspects of cerebral biopsy, and his recommendations remain valid today: (1)The patient has a chronic progressixe cerehral disorder with documented dementia. (2) All other possible diagnostic methods have already been tried and have failed to provide sufficient diagnostic certainty. (3) The general condition of the patient permits cerebral biopsy. (4) Several specialists are in agreement regarding the indication. (5) Informed consent is obtained from relatives. (6) Modern diagnostic tools, such as immunocytochemistry and electron microscopy, are used to the fullest capacity in the examination of the material obtained.

As with any intracranial surgical procedure involving the cerebral cortex, the risks of cerebral biopsy include anesthetic complications, hemorrhage, infections, and seizures. Guthkelch37 stated that the mortality associated with brain biopsy is not greater than that associated with general anesthesia. Cerebral biopsy, however can result in substantial morbidity. In our series, two of 14 patients suffered operative complications, intraparenchymal hemorrhage in one patient (patient 2) resulted in aphasia, while another patient (patient 10) developed a subdural hygroma, which was successfully treated, and recovered her baseline status.

The current diagnostic accuracy of cerebral biopsy in the evaluation of dementia is unknown. Most of the larger general series 34'38-41 were reported before computed tomography was available and included many pediatric cases presenting with genetic neurodegenerative disorders that are now more readily diagnosed by other means. For adults with dementia, less information is available. Katzman et al4 recently reviewed the literature concerning the diagnostic accuracy of cerebral biopsy for dementia and concluded that 75% of these procedures result in diagnostic material. Patient selection is very important, and the literature is heavily weighted toward patients with a clinical diagnosis of AD.35'42-44 Our study thus provides documentation of the diagnostic accuracy of cerebral biopsies in unselected patients with atypical dementia.

Autopsy follow-up is imperative in any dementia program,2 as a definitive diagnosis will not be made in a substantial proportion of patients. In our series, three patients died without a diagnosis, and autopsy was performed in all three. The diagnostic features were not present in the cortical area in which the biopsy was performed. In case 8, examination of the spinal cord revealed amyotrophic lateral sclerosis. Diffuse gliosis of the white matter was noted, which was the pathologic basis of the patient's dementia. In case 9. the spongiform change of CJD was focal, according to the pathologist's report; unfortunately, the tissue was not available for our review. In case 14, the diagnosis of Huntington's disease grade II/IV was made after close examination of the caudate nucleus. As one might predict, fewer autopsies were performed in the group with diagnostic biopsies; only two of five deaths in this category were followed by postmortem examinations. The diagnosis of AD was confirmed in case 4. In ease 3, the biopsy diagnosis of CJD was confirmed.

In summary, a series of 14 unselected cerebral biopsies performed for the diagnosis of atypical dementia was reviewed to define the spectrum of pathologic changes seen and to estimate the likelihood of obtaining diagnostic tissue. Histologic diagnoses of CJD, AD, diffuse Lewy body disease, Niemann-Pick disease type C, or anaplastic astrocytoma were made in seven patients. The high incidence of CJD in this population (four of 14 cases) emphasizes the need to use appropriate precautions when tissue from patients with unusual dementing illnesses is handled. Consultation among neurologist, neurosurgeons, neuroradiologists, and neuropathologists is essential to select appropriate patients and to choose the proper biopsy site. Demented patients with coexisting hemiparesis, chorea, athetosis, or lower motor neuron signs are unlikely to benefit from cortical biopsy.

This investigation was supported by Clinical Investigator Award PHS AG-00446 from the National Institute on Aging (Dr. Hulette) and by grant PHS SP50AG05128-03 from the Joseph and Kathleen Bryan Alzheimer's Disease Research Center (Drs Earl and Crain). Dr Hulette is a College of American Pathologists Foundation Scholar, Northfield, Ill.

The Authors thank Ms Bonnie Lynch and Ian Sutherland, PhD, for thier assistance.

1. Chui HC. Dementia: a review emphasizing clinicopathologic correlation and brain-behavior relationships. Arch NeuroI. 1989;46;806-814.

2. Jellinger K, Danielczyk W, Fischer P, Gabriel E. Clinicopathological analysis of dementia disorder's in the elderly, J Neurol Sci. 1990:95:239-258.

3. Katzman R. Alzheimer's disease. N Engl J Med. 1986;314:964-973.

4. Katzman R, Lasker B, Bernstein N. Advances in the diagnosis of dementia: accuracy of diagnosis and consequences of misdiagnosis of disorders causing dementia. In: Terry RD ed. Aging and the Brain. New York, NY: Raven Press; 1988: 17-62.

5. Khachaturian ZS. Diagnosis of Alzheimer's disease. Arch Neurol. 1985;42;1097-1105.

6. Koranyi E. The cortical dementias. Can J Psychiatry 1988;33;838-845.

7. Wilcock GK, Hope RA, Brooks DN, et al. Recommended minimum data to be collected in research studies on Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1989;52;693-700

8. Esiri MM, Oppenheimer DR. Diagnostic neuropathology. Boston, Mass: Blackwell Scientific publications Inc; 1989;236-239.

9. Sim M, Bale RN. Familial pre-senile dementia: the relevance of a histological diagnosis of Pick's disease. Br J Psychiatry. 1973;122;671-673.

10. Tomlinson BE, Corsellis JAN. Aging and the dementias, In Adams JH, Cosellis JAN, Duchen LW, eds. Greensfield's Neuropathology. New York, NY: John Wiley & Sons Inc; 1984:951-1025

11. F;endheim PE. The hunmn spongitbrm ence-phahq,athies. Ncl~rol Clim 19¥,1:2:281-29¥.

12. Brown P, Rodgers-Johnson P, Cathala L, Gibbs CJ, Gajdusek DC. Creutzfeldt-Jakob disease of long duration; clinicopathologic characteristics, Transmissibility and differential diagnosis. Ann Neurol. 1984;16:295-304.

13. Davanipour Z, Alter M, Sobel E. Creutzfeldt-Jakob disease. Neurol Clin. 1986:4:415-425.

14. Masters CL, Richardson EP: Subacute spongiform encephalopathy (Creutzfeldt-Jakob disease): the nature and progression of spongiform changes. Brain 1978;101:333-344.

15. Neatherlin JS. Creutzfeldt-Jakob disease. J Neurosci Nurs. 1988;20:309-313.

16. Nochlin D, Sumi SM, Bird TD, et al. Familial dementia with Prp-positive amyloid plaques: a variant of Gerstmann-Straussler syndrome. Neurology. 1989;39;910-918

17. Fisher CM. Binswanger's encephalopathy: a review. J Neurol 1989;236;65-79

18. Roman GC. Senile dementia of the Bins-wanger type. JAMA. 1987125811782-1788.

19. Burkhardt CR, Tilley CM, Kleinschmidt-DeMasters BK, de la Monte S, Norenberg MD, Sehneck SR. Diffuse Lewy hody disease and progressive dementia. Neurology. 1988;38:1520-1528.

20. Dickson DW, Davies P, Mayeux R, et al. Diffuse Lewy body disease: neuropathological and biochemical studies of six patients. Acta Neuropathol (Berl). 1987;75:8-15.

21. Gibb WRG. Neuropathelogy in movement disorders. J Neurol Neurosurg Psychiatry. 1989:supl:55-67.

22. Gibb WRG, Luthert PJ, Janota A. Lantos PL. Cortical Lewy body dementia: clinical features and classification. J Neurol Neurosurg Psychiatry. 1989;52;185-192.

23. MeKhann G. Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimers disease: report of the NINCDS-ADRDA work group. Neurology. 1984;34:939-944.

24. Brown P, Gibbs CJ Jr, Gajdusek DC, Cathala F, LaBauge R. Chemical disinfection of Creutzfeldt-Jakob disease virus. N Engl J Med. 1982;306;1279-1282.

25. Brumbach RA. Routine use of phenolipid formalin in fixation of autopsy brain tissue reduce risk of inadvertent transmission of Creutzfeldt-Jakob disease. N Engl J Med. 1988;319;654.

26. Rosenberg RN, White CL, Brown P, et al. Precautions in handling tissues, fluids and other contaminated materials from patients with documented or suspected Creutzfeldt-Jakob disease. Ann Neurol. 1986;12:75-77.

27. Lloyd B, Brinn N, Burger PC. Silver-staining of senile plaques and neurofibrillary change in paraffin-embedded tissues, J Histotech. 1985;8: 155-156.

28. Brady RO. Sphingomyelin lipidosis: Niemann-Pick disease. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS, eds. The Metabolic Basis of Inherited Disease. 5th ed. New York, NY: McGraw-Hill International Book Co; 1983:831-841.

29. Cogan DG, Chu FC, Reingold D, Barranger J. Ocular motor signs in some metabolic diseases. Arch Ophthalmol. 1981:99:1802-1808.

30. Lake BD. Lysosomal enzyme deficiencies. In: Adams JH, Corsellis JAN, Duchen LW. eds. Greenfield's Neuropathology. 4th ed. New York, NY:John Wiley & Sons Inc; 1984;491-572.

31. Pentchev PC. Comly ME, Kruth HS, et al. A defect in cholesterol esterification in Niemann-Pick disease (type C) patients. Proc Natl Acad Sci USA. 1985;82;8247-8251.

32. Vanier MT, Wenger DA, Comly ME, Rousson R. Brady RO, Pentchev PG. Niemann-Pick disease group C: clinical variability and diagnosis based on defective cholesterol esterification. Clin Genet. 1988;33;331-348.

33. Hulette CM, Earl NL, Anthony DC, Crain BJ. Adult onset Niemann-Pick disease type C: a case presenting with dementia and absent organomegaly. Clin Neuropathol. In press.

31. Pentchev PC, Comly ME, Kruth HS, et al. A defect in cholesterol esterfication in Niemann-Pick disease (type C) patients. Proc Natl Acad Sci USA. 1985;82;8247-8251

32. Vanier MT, Wenger Da, Comly ME, Rousson R, Brady Ro, Pentchev PG. Niemann-Pick disease group C: clinical variability and diagnosis based on defective cholesterol esterification. Clin Genet. 1988;33;331-348

33. Hulette CM, Earl NL, Anthony DC, Crain Bj. Adult onset Niemann-Pick disease type C; a case presenting with dementia and absen organomegaly. Cliln Neuropathol. In Press.

34. Groves R, Moller J. The value of the cerebral cortical biopsy. Acta Neurol Scand. 1966;42;477-482

35. Kaufman HH. Catalano LW. DiaGnostic brain biopsy: a series of 50 cases and a review. NeUROSURGERY. 1979:4:129-136.

36. Blemond A. Indications, legal and moral aspects of cerebral biopsies, In: Proceedings of Fifth International Congress of Neuropathology, Zurich, 1965, Princeton, NJ: Excerpta Medica; 1966:372-375.

37. Guthkelch AN. Brain biopsy in infancy and childhood. Dev Med Child Neurol, 1968;10;107-109.

38. Blackwood W, Cumings JN. The combined histological and chemical aspects of cerebral biopsies. In: Proceeedings of Fifth International Congress of Neuropathology, Zurich, 1965. Princeton, NJ: Excerpta Medica; 1966:364-371.

39. Green MA, Stevenson LD, Fonseca JE, Wortis SB. Cerebral biopsy in patients with presenile dementia. Dis Nerv Syst. 1952;13:303-307.

40. Sim M, Turner E, Smith WT. Cerebral biopsy in the investigation of presenile dementia, I: clinical aspects, Br J Psychiatry. 1966;112:119-125.

41. Turner E, Sim M. Cerebral biopsy in the investigation of presenile dementia, II: pathological aspects, Br J Phychiatry. 1966;112:127-133.

42. Bowen DM, Benton JS, Spillane JA. Smith CCT, Allen SJ. Choline acetyltransferase activity and histopathology of frontal neocortex from biopsies of demented patients. J Neurol Sci. 1982;57:191-202.

43. Neary D, Snowden JS, Bowen DM, et al. Cerebral biopsy in the investigation of presenile dementia due to cerebral atrophy. J Neurol Neurosury Psychiatry. 1986;49:157-162.

44. Neary D, Snowden JS, Mann DMA, et al. Alzheimer's disease: a corelative study. J Neurol Neurosurg Psychiatry. 1986;49:229-237.

Cerebral Biopsies in Dementia-- Hulette et al 31

Accepted for publication July 11, 1991. From the Department of Pathology, Division of Neuropathology (Drs Hulette and Crain), the Department of Medicine, Division of Neurology (Dr Earl), and the Department of Neurobiology (Dr. Crain), Duke University Medical Center, Durham, NC.

Arch Neurol--Vol 49, January 1992

TSS/5/7/01

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


http://www.vegsource.com/talk/lyman/messages/9254.html

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OTHER URLS OF INTEREST

1996). Stanley Prusinger, the scientist who coined the term prion, speculates Alzheimer's may in fact turn out to be a prion disease (Prusiner, 1984). In ...

http://www.cyber-dyne.com/~tom/Alzheimer_cjd.html#similar

http://216.239.39.100/search?q=cache:ujKcH823WucC:www.bse.org.uk/files/ws/s194.pdf+
PRION++ALZHEIMER%27S+BSE+INQUIRY&hl=en&start=4

http://www.bseinquiry.gov.uk/files/ws/s194.pdf

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

MULTIMODAL EVOKED POTENTIALS IN MOUSE MODELS OF NEURODEGENERATION

Transmissible spongiform encephalopathies and Alzheimer's disease are neurodegenerative disorders in which neuropathologic changes are associated with accumulation of prion protein and deposition of amyloid ß-protein, respectively. Recently, transgenic mice that overexpress a mutant human ß-amyloid precursor protein and mice devoid of prion protein were generated. However, few electrophysiologic studies in intact freely moving...

snip...

full text;

http://www.scripps.edu/research/sr2000/np11.html

Causes of Alzheimer's and "Mad-Cow" Diseases

Alzheimer's and "mad-cow" diseases are unique in that their infectious agents are not viruses or germs, but rather proteins. The brains of patients who suffered from Alzheimer's or cows that died of "mad-cow" disease show deposits of abnormal tissue called amyloid plaques. The primary component of these plaques is a protein called prion protein or PrP. Chemical and biochemical analysis showed that there was no difference in composition or primary structure between the normal, cellular form of PrP (PrPC, shown at right) and the disease form of PrP (PrPSc). Further analysis showed that PrPC can change into PrPSc when two of the a helices (shown in green) change into ß sheets. This ß sheet can then induce a similar change in another molecule of PrPC and hydrogen bond to it. The PrPSc 's then polymerize and come out of solution, forming the plaques found in Alzheimer's patients and mad cows. How the plaques cause the symptoms of the diseases is still not clear, but the prion protein holds the unique distinction of causing a disease solely through a small alteration in secondary structure.

full text;

http://genchem.chem.wisc.edu/netorial/modules/biomolecules/protein2/prot210.htm

importantly, recent findings indicating that the cellular accumulation of incorrectly folded proteins is the molecular basis of many diseases, including Alzheimer's Disease, Prion Diseases and Huntington Disease, underscore the importance of understanding the mechanisms of folding in vivo. Alzheimer's and prion disease appear to be caused by the generation of a "pathological" conformation in the newly translated protein that would otherwise fold to a normal conformation that does not produce the disease. In some model systems, molecular chaperones appear to play a role in this conformational change. Thus, developing approaches to study protein folding under physiological conditions is essential to understand how folding defects can lead to disease.

full text;

http://www.stanford.edu/group/frydman/interests.htm

Implications for Alzheimer's disease

Harris also has recently expanded his research to include Alzheimer's disease, which shares several features with prion diseases despite being non-infectious. Leonard Berg, M.D., professor of neurology and former director of the Alzheimer's Disease Research Center at the medical school, and other colleagues say Harris readily applies his extensive knowledge of cell biology to this area as well.

http://record.wustl.edu/archive/1998/02-12-98/3678.html

RESEARCH LETTERS

Early-Onset Familial Alzheimer Disease With Coexisting [beta] -Amyloid and Prion Pathology

To the Editor: Familial Alzheimer disease (AD) with early onset has been linked to 3 different genes with an autosomal dominant mode of inheritance: [beta] -amyloid, protein precursor, and the presenilins 1 and 2, representing not more than 50% of all cases of early-onset AD cases.1 Thus, the genetic defect remains unexplained in at least half of the families with histories of early onset of AD. We have recently described such a Swiss family whose members presented with a standard clinical and neuropathologic profile of AD.2 In particular, severe neurofibrillary tangle degeneration was present in the hippocampus and in several cortical areas, together with a large amount of [beta] -amyloid deposits and senile plaques (SPs). However, known mutations have not been found, either in the [beta] -amyloid precursor protein or in the presenilin 1 and 2 genes.2 We now report that the brains of 5 deceased members of this family, from 2 generations, present a coexisting [beta] -amyloid and prion protein (PrP) pathology.


Methods <http://jama.ama-assn.org/images/dot_lgray_999999.gif>

Five available cases with clinical AD were diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria. The age at onset of disease ranged from 43 to 64 years (mean, 55.8 years) and age at death ranged from 55 to 81 years (mean, 67.4 years). In addition, 4 of the 5 cases had epileptic features. Serial frozen sections (50 µm thick) through the temporal and frontal cortex of the 5 formalin-treated brains were pretreated with formic acid. They were then processed using monoclonal antibodies against amyloid- [beta] 40 peptide (1:100; [Sigma] ) and against PrP106-126 (1:200; produced by one of us).3 The latter antibody specifically marks the pathological isoform of the PrP and does not cross-react with [beta] -amyloid deposits. In addition, double immunostaining using successive anti- [beta] -amyloid and anti-PrP106-126 antibodies was performed.


Results <http://jama.ama-assn.org/images/dot_lgray_999999.gif>

In all 5 cases, the cerebral cortex revealed spongiform changes, mainly in superficial layers, and some degree of gliosis. Neurofibrillary tangle and neuritic plaques revealed by Gallyas were numerous in all cortical regions including the primary visual area. In addition, frequent [beta] -amyloid-positive SPs were observed, together with SP stained by the monoclonal antibody against PrP106-126. Successive sections alternately stained with the 2 antibodies showed that both [beta] -amyloid and PrP106-126 positive SP are deposited in all layers of the frontal and temporal cortex. A population of SP, marked on 2 serial sections with both antibodies, was positive for both [beta] -amyloid and PrP106-126. Double-stained sections with [beta] -amyloid and PrP106-126 antibodies further demonstrate that 3 populations of plaques exist: only [beta] -amyloid, only PrP106-126 positive, or positive for both antibodies (Figure 1) and a majority of SPs (>50%) are immunopositive for both [beta] -amyloid and PrP106-126 antibodies. Comparatively, the relative proportion of SPs marked for each antibody alone is smaller. In particular, SPs marked for PrP106-126 represent approximately 5% to 10% of the whole population.


Comment <http://jama.ama-assn.org/images/dot_lgray_999999.gif>

Coexistence of Creutzfeldt-Jakob disease (CJD) and AD in some patients has been described but appears mainly related to age in patients proven to have CJD.4 However, since the individuals in the Swiss family died over a long interval and were all similarly affected, it is unlikely that CJD is purely coincidental. On the other hand, familial Gerstmann-Straüssler-Scheinker disease can present a variant with concomitant neurofibrillary tangle and prion-positive plaques, but not [beta] -amyloid-positive plaques. Within this variant, 2 mutations in the gene for the PrP have been identified in 2 different families, and the clinical profile with cerebellar ataxia and extrapyramidal signs5 differs from our findings.2 Base pair deletion in the prion gene segregating as an uncommon polymorphism has been described in a family with a history of late-onset AD, but there is no neuropathological confirmation and the genetic association is uncertain.6

Thus, the data presented herein support the existence of a possible new subtype of familial early-onset AD with a concomitant [beta] -amyloid and prion brain pathology, together with a massive neurofibrillary tangle degeneration. Although all known mutations have been excluded in the coding regions of the AD genes, numerous candidate chromosome sites, either in the AD genes outside the coding regions or in other genes including PrP, must be considered.


G. Leuba, PhD, PD K. Saini, PhD University Psychogeriatrics Hospital Lausanne-Prilly, Switzerland

A. Savioz, PhD Y. Charnay, PhD University of Geneva School of Medicine Geneva, Switzerland


1. Cruts M, Van Broekhoven C. Molecular genetics of Alzheimer's diease. Ann Med. 1998;6:560-565.

2. Savioz A, Leuba G, Forsell C, et al. No detected mutations in the genes for the amyloid precursor protein and presenilins 1 and 2 in a Swiss early-onset Alzheimer's disease family with a dominant mode of inheritance. Dement Geriatr Cogn Disord. 1999;10:431-436. MEDLINE

3. Boris N, Mestre-Frances N, Charnay Y, Tagliavini F. Spontaneous spongiform encephalopathy in a young adult rhesus monkey. Lancet. 1996;348:55. MEDLINE

4. Hainfellner JA, Wanschitz J, Jellinger K, Liberski PP, Gullotta F, Budka H. Coexistence of Alzheimer-type neuropathology in Creutzfeldt-Jakob disease. Acta Neuropathol (Berl). 1998;96:116-122. MEDLINE

5. Ghetti B, Tagliavini F, Giaccone G, et al. Familial Gerstmann-Straüssler-Scheinker disease with neurofibrillary tangles. Mol Neurobiol. 1994;8:41-48. MEDLINE

6. Perry RT, Go RCP, Harrell LE, Acton RT. SSCP analysis and sequencing of the human prion protein gene (PRNP) detects two different 24 bp deletions in an atypical Alzheimer's disease family. Am J Med Genet. 1995;60:12-18. MEDLINE


Funding/Support: This study was supported by grants 3100-045960.95 and 3100-043573.95 from the

 

[flounder]

Funding/Support: This study was supported by grants 3100-045960.95 and 3100-043573.95 from the Swiss National Science Foundation.

http://jama.ama-assn.org/issues/v283n13/ffull/jlt0405-5.html

Slide show

... Many neurodegenerative disorders -- such as prion diseases, Parkinson's disease, Huntington's disease, Alzheimer's disease, frontotemporal dementia -- are ...

http://www.nature.com/nrm/journal/v1/n3/slideshow/nrm1200_217a_F1.html

Occasional PrP plaques are seen in cases of Alzheimer's Disease

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full text;

http://www.bseinquiry.gov.uk/files/ws/s310.pdf

2 3 Once isolated, the agent must be capable of reproducing the disease in experimental animals. 4 The agent must be recovered from the experimental disease produced. 3. In the case of transmissible spongiform encephalopathies (TSEs), these postulates are not fulfilled in the following ways: 4. Unfulfillments of Postulate 1. 4.1 Transgenic mice with a codon 102 mutation involving a leucine substitution spontaneously develop spongiform encephalopathy with no detectable mutant prion protein (PrPsc). (Ref. Hsiao K.K. et al. Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science (1990) 250: 1587-1590.) (J/S/250/1587) 4.2 Spongiform encephalopathy in zitter rats does not involved PrP. (ref. Gomi H. et al. Prion protein (PrP) is not involved in the pathogenesis of spongiform encephalopathy in zitter rats. Neurosci. Lett (1994) 166: 171-174.) (J/NSC/166/171) 4.3 Many viruses and retroviruses can produced spongiform encephalopathies without PrPsc involvement. (Ref. Wiley C.A. Gardner M. The pathogenesis of murine retroviral infection of the central nervous system. Brain Path (1993) 3: 123-128.) (J/BRP/3/123) 4.4 Experiments involving the transmission of the 'BSE agent' in mice produced symptoms of TSE, but in 55% no PrPsc could be detected. (Ref. Lasmesaz. C. et al. Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science (1997) 275: 402- 405.) (J/S/275/402) 5. Unfulfillment of Postulate 2 5.1 Occasional PrP plaques are seen in cases of Alzheimer's Disease, where they coexist with the more usual beta amyloid plaques. (Ref. Baker H. F. Ridley R.M. Duchen L.W. Crow T.J. Bruton C.J. Induction of beta

full text;

http://www.bse.org.uk/files/ws/s310.pdf

Wednesday, 23 August, 2000, 23:54 GMT 00:54 UK Alzheimer's and CJD 'similar' [Brain] Rogue proteins are thought to cause degenerative brain disorders Scientists have discovered striking similarities between Alzheimer's disease and the human form of mad cow disease, vCJD.

They believe the breakthrough could lead to drugs to treat both conditions.

Both are marked by a gradual and ultimately fatal deterioration of the brain and both are associated with rogue proteins.

Now Professor Chi Ming Yang, of Nankai University in Tianjin, China, has discovered that these proteins have very similar structures.

This could mean that the molecular mechanism underlying Alzheimer's disease and vCJD is the same.

Professor Yang used a computer model to map the prion protein associated with vCJD and the amyloid precursor protein associated with early stage Alzheimer's.

He found that the two proteins had a similar pattern of component parts known as amino acids.

Each are made up of a reductive amino acid followed by three non-reductive amino acids.

Reductive amino acids are more prone to damage by free radicals - charged oxygen particles that can disrupt the DNA of the body's cells.

Normally, the body can clear itself of free radicals. But with age, this system may fail.

When enough free radicals accumulate to damage a protein molecule it can malfunction.

Scientists believe this mechanism may lead to Alzheimer's, the most common cause of dementia, affecting an estimated 12 million people worldwide.

The disease is characterised by include messy "tangles" of nerve fibres and "plaques" rich in the amyloid proteins.

CJD is the human version of bovine spongiform encephalitis (BSE or mad cow disease).

It occurs naturally in about one in a million people but a new version, vCJD, has been linked with eating BSE-infected meat.

BSE and vCJD are believed to be caused by prion proteins that do not fold normally.

http://news.bbc.co.uk/hi/english/health/newsid_892000/892819.stm

Stanley Prusiner, M.D.

Stanley Prusiner, M.D., a neurobiologist at the University of California at San Francisco, was awarded the 1997 Nobel Prize in Medicine for his groundbreaking discovery and definition of a new class of disease-causing agents called prions (pronounced pree-ons). The Nobel Prize, is the most prestigious award given for research in medicine.

Dr. Prusiner's award is the culmination of 25 years of sometimes controversial research on the prion, a natural human protein that, under certain conditions, can interact with other prion proteins, ultimately forming harmful deposits in the brain. The American Health Assistance Foundation (AHAF) has awarded more than $1.2 million in research grants through its Alzheimer's Disease Research program to Dr. Prusiner to develop his prion theory as a model for Alzheimer's disease. According to AHAF President Eugene Michaels, "Dr. Prusiner has proven that the most promising discoveries are often the result of innovative scientific inquiry. We are honored to have played a part in Dr. Prusiner's groundbreaking research."

Prions have been implicated in dementia-causing diseases such as mad cow disease and scrapie in animals, and Creutzfeldt-Jakob Disease (CJD) and Gerstmann-Straussler-Scheinker syndrome (GSS) in humans. Unlike infectious agents such as bacteria, viruses and parasites, whose ability to grow and reproduce is governed by genetic material made up of RNA and DNA, prions appear to be made up entirely of proteins with no accompanying DNA or RNA. Prions are present in normal cells, and the gene that codes for the production of the prion protein is part of a normal human chromosome.

Since 1985, the American Health Assistance Foundation has supported studies of the structures and properties of prions, and investigations that led to the purification and identification of the prion protein in the brains of scrapie-infected sheep. AHAF also awarded a grant to Dr. Prusiner to study CJD and GSS, using molecular biology methods to introduce genes from mutated prion proteins into mice to create an animal model for these diseases. His current AHAF grant is focused on the development of a new system to determine when in the life of a mouse the prion protein leads to disease. He is also studying a method to prevent prion disease by blocking prions from converting normal proteins into more prions.

There are similarities between the loss of brain function in prion diseases and in Alzheimer's disease, and an understanding of how prion diseases begin and develop will add to our understanding of what happens to the brain in Alzheimer's disease. Dr. Prusiner's research may one day lead to a treatment and a cure for Alzheimer's.

http://www.ahaf.org/alzdis/about/prusiner.htm

Date: Posted 8/24/2000

"Strikingly Similar" Protein May Be In Alzheimer's And Mad Cow Disease Washington D.C., August 23 -- A "striking similarity" between proteins involved in the early stages of Alzheimer's disease and mad cow disease was described here today at the 220th national meeting of the American Chemical Society, the world's largest scientific society. The theory, if verified by other researchers, could help focus efforts to develop preventive drugs, according to the study's lead researcher, Chi Ming Yang, Ph.D., a professor of chemistry at Nankai University in Tianjin, China.

Prion diseases -- which include, among others, neurodegenerative diseases such as mad cow disease and its human counterpart, Creutzfeldt-Jakob disease -- are caused by a malfunctioning prion protein. In Alzheimer's disease, another neurodegenerative disease, the amyloid precursor protein has been implicated.

Using computer modeling, Yang discovered a similar pattern of amino acids in the prion protein and the amyloid precursor protein: a reductive amino acid followed by three non-reductive amino acids.

"This suggests a common molecular mechanism underlying the initiation stages of sporadic Alzheimer's disease and both sporadic and genetic prion diseases," says Yang.

Reductive amino acids are more prone to damage by oxygen-containing free radicals (molecules with a highly reactive unpaired electron) than other amino acids, explained Yang. Normally, the body can clear itself of free radicals. But with age, this system may fail. When enough free radicals accumulate to damage a protein molecule, it can malfunction, he says.

Proteins typically fold into specific three-dimensional structures that determine their functions. A malfunctioning protein may remain partially unfolded, which can place different amino acids in close proximity, Yang explained. In the case of Alzheimer's and prion diseases, the reductive amino acids in close proximity can lead to the formation of protein plaques, according to Yang.

Although Alzheimer's and prion diseases seem to start in similar ways, they progress differently. This may explain why Alzheimer's disease advances at a much slower pace than Creutzfeldt-Jakob disease, says Yang.

The paper on this research, PHYS 460, will be presented at 7 p.m., Wednesday, Aug. 23, in the Washington Convention Center, Exhibit Hall D.

Chi Ming Yang, Ph.D., is a chemistry professor at Nankai University, Tianjin, China.

A nonprofit organization with a membership of 161,000 chemists and chemical engineers, the American Chemical Society publishes scientific journals and databases, convenes major research conferences, and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.

http://www.sciencedaily.com/releases/2000/08/000824081151.htm

http://www.sciencedaily.com/releases/2000/08/000824081151.htm


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Some references that may be interesting on the topic...

References. Aguzzi, A. and Weismann, C. Prion Research: the Next Frontiers. Nature, Vol.389 pp.796-79 ,1997. Alper , T.; Cramp, W.; Haig , D. and Clarke, M. Does the agent of scrapie replicate without nucleic acid?, Nature, Vol.214, pp.764-766.1967 Aldudo, J.; Bullido, M.J; De Miguel, C.; Valdivieso, F.; and Vazquez, J. Presenilin-1 genotype[2/2] is associated with late onset Alzheimer's disease in Spanish patients. Alzheimer's Res. Vol.3, pp.141-143.1997 Avila , J. and Colaco, A.L. The role of sulphated glycosaminoglycans in Alzheimer's disease.: a hypothesis. Alzheimer's Res., Vol.3,pp.77-81.1997 Avila, J. Modification of proteins related with the onset of Alzheimer's disease: Tau phosphorilation, glycosylation and oxydation in Alzheimer's disease. Current Drugs , Vol.2,pp.141-143.1997 Baldwin , M.; James , T.; Cohen, F.; and Pruisiner , S. The three-dimensional structure of prion protein : implications for Prion disease. Biochemical Society Transactions , Vol.26, pp.481-486.1998 Baldwin, M.; Pan ,K.; Nguyen , J.; Huang, Z. Groth, D.; Serban, A. et al. Spectroscopic Characterization of conformational differences between PrPc and PrPsc-An Alpha-helix to Beta-sheet transition. Philosophical Transactions of the Royal Society of London, series B-Biological Sciences,Vol.343, number 1306, pp-435-441.1992 Ball, M. Features of Creutzfeldt-Jakobs disease in brains of patients with familial dementia of Alzheimer's type. Canadian Journal of Neurological Sc.Vol.7 , pp.51-57.1980 Banissi-Sabourdi, C.; Planques, B.; David, J.P.; Jeannin, C.; Potel , M; Bizien, M.; Di Menza, C.; Brugère -Picoux, J.; Brugère, H.; Chatelain , J. Electroanalytical characterization of Alzheimer's disease and ovine spongiform encephalopathy by repeated cyclic voltametry at a capillary graphite paste electrode .Bioelectrochemistry and Bioenergetics. Vol. 28, pp.127-147.1992 Bernouli, C.; Siegfried, J.; Baumgartner,g. et al. Danger of accidental person to person transmission of Creutzfeldt-Jakobs disease by surgery . The Lancet.Vol.1,pp.478-479.1997 Borner, C.; Oliver, r.; Martinou, I.; Mattman ,C.; Tschopp, J.; and Martinou ,J.C. Dissection of functional domains in bcl-2 alpha by site directed mutagenesis . Biochemical Cellular Biology.Vol.72, pp463-469.1994 Brandner, s.; Isenmann, S; Raeber, A.; Fischer ,M.; Sailer, A.; Koyba et al. normal host prion protein necessary for scrapie-induced neurotoxicity.Nature.Vol.379, pp.339-343.1996 Braham, J . Ceutzfeldt-Jakob Disease: treatment by Amantidine. Brit. Med . J. Vol. 4, pp.213-213.1971 Brown, P.; Cathala, F.; and Gjdusek, D.C. Creutzfeldt-Jakob disease in France III. Epidemiological study of 170 patients dying during the decade 1968-1977. Ann. Of Neur.vol.6, pp.438-446.1979 Brugère, H.; Banissi, C.; Brugère-Picoux, J.; Chatelain, J. et Buvet, R. Recherche d'un temoin biochimique urinaire de l'infection du mouton par la tremblante. Bull. Acad. Vet. de France.Vol.64, pp.139-145.1991 Brugère, H.; Banissi, C.; Brugère-Picoux ,J .;Chatelain, J.; Tournaire, M.C et Buvet, R. Electrochemical analysis of urine in Alzheimer's patients and ruminants with spongiform encephalopaties ( scrapie and BSE) .III Int. Symp. on Transmissible subacute spogiform encephalopaties: Prion diseases, Paris, Val de Grace, 18-20 March.1996 Bruce, M.; Will, r.; Ironside, J.; McConnell, I.; Dummond , D,; and Suttie, A. Transmission to mice indicates that "new variant" CJD is caused by BSE agent. Nature. Vol.389, pp.498-501.1997 Byeler, H.; Aguzzi, A.; Sailer, A.; Greiner, r.; Autenreid, P.; Aguet, M.. and Weissman, C. Mice devoid of PrP are resistant to scrapie. Cell.vol.73, pp.1339-1347.1993 Carpenter, C.; Fishl, M.; Hammer, S.M; et al . Anti-retroviral therapy for HIV infection in 1996: Recommendations of an international panel. JAMA. Vol. 276,pp.146-154.1996 Cathala, F.; Brown, P.; Rahison, S et al. Maladie de Creutzfeldt-Jakob en France. Revue Neurologique (Paris).Vol.7,pp56-62.1982 Caughey, W.; Raymond, L .; Horiuchi, M.; and Caughey, B. Inhibition of protease-resistant prion protein formation by porphyrins and phtalocyanines.PNAS.Vol.95.Iss.21,pp.12117-12122.Oct.17th,1998. Cohen, F.; Pan, K.; Huang, Z; Baldwin, M.; Fletterick, R. and Pruisiner, S. Structural clues to prion replication.Science.Vol.264, pp.530-531. 1994 Collinge, J.; and Hawke, S. B lymphocytes in prion neuroinvasion: central or peripheral players?. Nature Medicine .Vol.4,pp.1369-1370.1998. Collinge, J. and Palmer, M. Prion Diseases. Oxford University Press.1997 Collinge, J.; Whittington ,M.; Siddle, K. et al. Prion protein is necessary of synaptic formation. Nature. Vol.370, pp.277-295.1994 Cook, B.H.; Ward, B.; and Austin, J. Studies in ageing in the brain IV. Familial Alzheimer's disease : elation to transmissible dementia, aneuploidy and microtubular defects. Neur.Vol.29, pp.1402-1412.1979 De Armond, S.; Sanchez, h.; Yehiely, Q et al. Selective Neuronal targeting in prion disease.Neuron.Vol.19, pp.1337-1348.1997 De Wolfe, F.; Lukashnov, V. Danner, S et al .Clearance of HIV-1 following treatment with two, three, four or five anti-HIV drugs. Program and abstracts of the 5th conference on retroviruses and opportunistic infections.Feb.1-5th. Chicago, Ill.1998.Abs.384 Garrett, L. The Coming Plague. Penguin USA. 1995 Gibbs, T.; Baldwin, M.; Lloyd, D. et al. Predicted alpha-helical regions of the prion protein when synthesized as peptides from amyloid. PNAS.Vol.89,pp.10940-10944.1992 Goudsmith, J.; Morrow, C.; Asher, D. et al. Evidence for and against the transmissibility of Alzheimer's disease.Neurology.Vol.30pp.945-950.1980 Herishanu, Y. Antiviral drugs in Creutzfeldt-Jakob disease. J. of Am. Soc. of Geriatrics.Vol.21,pp.229-273.1973 Ikeda, K.; Kawada, N.; Wang ,Y. et al .Expression of cellular prion protein in activated hepatic stellate cells. Am. J. of Path.Vol.6,N.6, pp.1695-1700.1999 Jellinger, K.; and Seitelberger, F. Spongy degeneration in the central nervous system in infancy. Curr. Top. in Path.Vol.53, pp.90-160.1970 Kimberlin, R. and Walker , C. Anti-viral compound effective against experimental scrapie. The Lancet.Vol.2, pp.591-592.1979 Knusel, B. and Hefti ,Development of cholinergic pedunculopontine neurons in vitro: comparison with cholinergic septal cells and response to nerve growth factor, ciliary neurothrophic factor and retinoic acid. J. of Neurosc. Res. Vol.21,pp.365-375.1988 Manuelidis, E.; Manuelidis, L.; Pincus , J. et al. Transmission from man to hamster of Creutzfeldt-Jakob disease with clinical recovery. The Lancet. Vol.2.pp.40-42.1978 Munoz-Montano, J.; Moreno, F.; Avila, J. et al. Lithium inhibits Alzheimer's disease-like tau protein phosphoryllation in neurons .FEBS Lett.Vol.411,pp.183-188.1997 Perez, M.; Wandosell, F.; Colaco, C. and Avila, J. Sulphated glycosaminoglycans prevent neurotoxicity of human prion protein fragment . Pruisiner,S.Prions.PNAS.1998 Sadler, I.; Smith, D.; Sherman, M. et al .sulphated compounds attenuate Beta-amyloid toxicity by inhibiting its association with cells .Neuroreport.Vol.7,pp.49-53.1995 Sadler, I.; Hawtin, S.; Tailor, V. et al . Glucosaminoglycans and sulphated polyanions attenuate neurotoxic effects of beta-amyloid. Biochem. Soc. Trans. Vol.23,p.1065.1995 Sukhalayan,C.; Khalequz, Z.; Hoon, R.; Conforto, A.; and Rajiv, R. Sequence-Selective DNA binding drugs Mitramyacin A and Chromomyacin A3 are potent inhibitors of neuronal apoptosis induced by oxidative stress and DNA damage in cortical neurons.Ann.Neurol.Vol.49,pp.345-354.2001

Diagnosis and Reporting of Creutzfeldt-Jakob Disease T. S. Singeltary, Sr; D. E. Kraemer; R. V. Gibbons, R. C. Holman, E. D. Belay, L. B. Schonberger

http://jama.ama-assn.org/issues/v285n6/ffull/jlt0214-2.html


IN STRICT CONFIDENCE

TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES


http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf


Subject: Re: Hello Dr. Manuelidis Date: Fri, 22 Dec 2000 17:47:09 -0500 From: laura manuelidis <[email protected]> Reply-To: [email protected]. Organization: Yale Medical School To: "Terry S. Singeltary Sr." <[email protected]>

References: <[email protected]> <[email protected]>
<[email protected]> <[email protected]>
<[email protected]> <[email protected]>
<[email protected]>

Dear Terry,

One of our papers (in Alzheimer's Disease Related Disord. 3:100-109, 1989) in text cites 6 of 46 (13%) of clinical AD as CJD. There may be a later paper from another lab showing the same higher than expected incidence but I can't put my hands on it right now. We also have a lot of papers from 1985 on stating that there are likely many silent (non-clinical) CJD infections, i.e. much greater than the "tip of the iceberg" of long standing end-stage cases with clinical symptoms. Hope this helps.

best wishes for the new year laura manuelidis

"Terry S. Singeltary Sr." wrote: > > Hello again Dr. Manuelidis, > > could you please help me locate the 2 studies that were > done on CJD where it showed that up to 13% of the people > diagnosed as having Alzheimer's actually had CJD. > trying to find reference... > > thank you, > Terry S. Singeltary Sr.


4.5 MILLION DEMENTED ALZHEIMER'S PATIENTS, HOW MANY ARE CJD/TSEs ???

HOW CAN ONE-IN-A-MILLION BE ACCURATE WHEN CJD IS NOT REPORTABLE,

AND WHEN THE ELDERLY DO NOT GET AUTOPSIED??????

TSS

REFERENCE

More Evidence Mad Cow Same
As CJD And Alzheimer's
1-24-3
Date: Fri, 24 Jan 2003 From: Terry S. Singeltary Sr. Subject: Re: CJD $ Alzheimer's


(http://www.boston.com/news/globe/editorial_opinion/editorials/articles/2006
/01/02/the_value_of_autopsies/)
> THE BOSTON GLOBE -- Monday January 2, 2006
> Editorial
> The value of autopsies
>
> SIX YEARS AGO, the federal Institute of Medicine deplored the annual toll
of
> 98,000 deaths caused by errors in US hospitals. Since then, progress has
> been made in some approaches to curbing medical mistakes, but there has
been
> little advance in one of the best correctives: more routine use of
autopsies.
>
> Autopsies are a low-tech but highly effective way to learn answers to
> medical puzzles that MRIs and other imaging devices often cannot explain.
> Until the 1960s, nearly half of all patients who died in hospitals were
> autopsied, but the rate has fallen below 5 percent now. No campaign to
> improve healthcare will be complete without a concerted effort by the
major
> hospital accrediting agency and Medicare to ensure that this
quality-control
> check is used more often.
>
> Autopsies are routinely done by state medical examiners in cases of
crimes,
> accidents, and many deaths that occur outside of hospitals.
>
> Recently, the state's new chief medical examiner, Dr. Mark Flomenbaum,
> lamented that relatively few autopsies are occurring in hospitals. He
> attributed this to doctors' reluctance to broach or press the subject with
> family of the deceased.
>
> Everyone would benefit if doctors were more willing to explain to loved
ones
> how much medicine can learn from this procedure.
>
> In 1999, autopsies in New York City uncovered the first US cases of West
> Nile disease.
>
> The victims had been misdiagnosed as suffering from St. Louis
encephalitis.
> More frequent autopsies would also result in earlier alarm bells if avian
> flu or some other new and highly contagious disease arrives on these
shores.
>
> Modern diagnostic measures might make autopsies less necessary but not
> superfluous, as shown in studies like the one published in 1998 by the
> Journal of the American Medical Association. Reporting on 1,100 autopsies
> done over 10 years in New Orleans, the study found that of 250 cancers
> detected, 44 percent had been undiagnosed or misdiagnosed.
>
> The then-editor of JAMA, Dr. George Lundberg -- a longtime advocate of
> greater use of autopsies -- has called physicians' faith in their
technical
> knowledge "a vast cultural delusion."
>
> An autopsy can also be of use to survivors.
>
> While the procedure may confirm that a middle- aged person died of the
heart
> attack diagnosed by the physician, doctors might also learn that the
patient
> was developing, without symptoms, one of the more inheritable cancers -- a
> warning to his family.
>
> Historically, the autopsy has been at the center of humankind's knowledge
of
> how the body works. If the country is serious about reducing the rate of
> medical errors and quickly detecting the arrival of lethal new infections,
> autopsies need to play a greater role.
>
>

 

[Econ101]

It seems MacDonalds is on the warpath to protect the children it feeds (and incidentally its business). I wish the USDA and FDA had the same thing in mind.

Experts: Defense Against Mad Cow Falls 'Woefully Short'

POSTED: 8:27 am MST January 5, 2006
Email This Story | Print This Story

WASHINGTON -- Researchers and the nation's No. 1 burger seller say the government is not fully protecting animals or people from mad cow disease.

Stronger steps are needed to keep infection from entering the food chain for cattle, the critics wrote in comments to the Food and Drug Administration.

The group includes McDonald's Corp., seven scientists and experts and a pharmaceutical supplier, Serologicals Corp.

The government proposed new safeguards two months ago, but researchers said that effort "falls woefully short" and would continue to let cattle eat potentially infected feed, the primary way mad cow disease is spread.
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"We do not feel that we can overstate the dangers from the insidious threat from these diseases and the need to control and arrest them to prevent any possibility of spread," the researchers wrote.

McDonald's said the risk of exposure to the disease should be reduced to zero, or as close as possible. "It is our opinion that the government can take further action to reduce this risk," wrote company Vice President Dick Crawford.

In people, eating meat or cattle products contaminated with mad cow disease is linked to a rare but fatal nerve disorder, variant Creutzfeldt-Jakob Disease.

No one is known to have contracted the disease in the United States. The disease has turned up in two people who lived in the U.S., but it's believed they were infected in the United Kingdom during an outbreak there in the 1980s and 1990s.

The U.S. has found two cases of mad cow disease in cows. Since the first case, confirmed in December 2003 in a Canadian-born cow in Washington state, the government has tested more than half a million of the nation's 95 million cows. The second case was confirmed last June in a Texas-born cow.

"While this surveillance has not uncovered an epidemic, it does not clear the U.S. cattle herd from infection," the researchers said.

The primary firewall against mad cow disease is a ban on using cattle remains in cattle feed, which the U.S. put in place in 1997. However, the feed ban has loopholes that create potential pathways for mad cow disease. For example, using restaurant plate waste is allowed in cattle feed.

The Food and Drug Administration proposed in October to tighten the rules, but critics said glaring loopholes would remain.

The FDA, which regulates animal feed, accepted public comments on the proposal through last month. An agency spokeswoman said Wednesday it would be inappropriate to respond to those comments.

The critics said their biggest concern is that tissue from dead animals would be allowed in the feed chain if brains and spinal cords have been removed. Brains and spinal cords are tissues that can carry mad cow disease.

In dead cattle that had the disease, infection had spread beyond brains and spinal cords. Leaving tissue from dead cattle in the feed chain would negate FDA's attempt to strengthen its safeguards, the critics said.

The most effective safeguards, they said, would be to:

* Ban from animal feed all tissues considered "specified risk materials" by the Agriculture Department, which requires that such materials be removed from meat that people eat. This includes tissues beyond the brain and spinal cord, such as eyes or part of the small intestine.

* Ban the use of dead cattle in animal feed.

* Close loopholes allowing plate waste, poultry litter and blood to be fed back to cattle.

Within the meat industry, many say the FDA proposal is effective, although some companies contend new rules are unneeded. The American Meat Institute Foundation, which represents meat processing companies, backs the FDA proposal.

"To take out the most potentially infected material, and that would be brains and spinal cords, that removes about 90 percent of the potential infectivity that is in an animal -- if it's infected," said Jim Hodges, AMI Foundation president.

Mad cow disease is the common name for bovine spongiform encephalopathy, or BSE, a degenerative nerve disease in cattle.

 

[flounder]

9 December 2005
Division of Dockets Management (RFA-305)
Food and Drug Administration
5630 Fishers Lane
Room 1061
Rockville, MD 20852
Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273)
Substances Prohibited From Use in Animal Food and Feed
Dear Sir or Madame:
Serologicals Corporation is a global provider of biological products to life science companies.
The Company's products are essential for the research, development and manufacturing of
biologically based diagnostic, pharmaceutical and biological products. customers include
many of the leading research institutions, diagnostic and pharmaceutical companies throughout
the world. The Company's products and technologies are used in a wide variety of applications
within the areas of neurobiology, cell signaling, oncology, angiogenesis, apoptosis,
developmental biology, cellular physiology, hematology, immunology, cardiology, infectious
diseases and molecular biology.
A number of our products are derived from bovine blood or other bovine tissues sourced in the
United States, hence the overall health of the national herd is extremely important to our
company as well as to our customers and their patients. Some of our bovine based products are
used in the manufacture of vaccines and drugs for humans, hence it is critical that all measures
are taken to assure these are safe and free from disease especially Bovine Spongiform
Encephalopathy (BSE). The most effective way to insure this is to create a system which
processes cattle that are BSE free. As a company there are a number of precautions that we can
take by our strict specifications but many of the needed precautions require the force of federal
regulation, hence we appreciate the opportunity to submit comments to this very important
proposed rule.
After the identification of bovine spongiform encephalopathy (BSE) in indigenous North
American cattle, the U.S. Department of Agriculture (USDA) responded rapidly to implement
measures to protect public health in regard to food. Our company recognizes and supports the
importance of the current feed ban which went into effect in August 1997. However, given what
is known about the epidemiology and characteristically long incubation period of BSE, we urge
5655 Spalding Drive * Norcross, GA 30092
678-728-2000 * 800-842-9099 * Facsimile 678-728-2299
www.serologicais.com
Division of Dockets Management (HFA-305)
Page 2
9 December 2005
the FDA to act without further delay and implement additional measures which will reduce the
risk of BSE recycling in the US cattle herd.
We feel that for the FDA to provide a more comprehensive and protective feed ban, specified
risk materials (SRMs) and deadstock must be removed from all animal feed and that legal
exemptions which allow ruminant protein to be fed back to ruminants (with the exception of
milk) should be discontinued.
SRMs, as defined by the USDA, are tissues which, in a BSE infected animal, are known to either
harbor BSE infectivity or to be closely associated with infectivity. If SRMs are not removed,
they may introduce BSE infectivity and continue to provide a source of animal feed
contamination. Rendering will reduce infectivity but it will not totally eliminate it. This is
significant as research in the United Kingdom has shown that a calf may be infected with BSE
by the ingestion of as little as .OOl gram of untreated brain.
The current proposed rule falls short of this and would still leave a potential source of infectivity
in the system. In fact by the FDA's own statement the exempted tissues which are known to
have infectivity (such as distal ileum, DRGs, etc) would cumulatively amount to 10% of the
infectivity in an infected animal, This proposed rule would still allow for the possibility that
cattle could be exposed to BSE through:
1. Feeding of materials currently subject to legal exemptions from the ban (e.g., poultry
litter, plate waste)
2. Cross feeding (the feeding of non-ruminant rations to ruminants) on farms; and
3. Cross contamination of ruminant and non-ruminant feed
We are most concerned that the FDA has chosen to include a provision which would allow
tissues from deadstock into the feed chain. We do not support the provision to allow the removal
of brain and spinal cord from down and deadstock over 30 months of age for several reasons.
These are the animals with the highest level of infectivity in tissues which include more than
brain and spinal cord. We do not feel that there can be adequate removal and enforcement of this
regulation especially during warmer weather. In addition there is emerging information that at
end stage disease, infectivity may also be included in additionai tissues such as peripheral nerves
(Buschmann and Groschup, 2005).
Leaving the tissues from these cattle in the animal feed chain will effectively nullify the intent of
this regulation. This point is illustrated by the 2001 Harvard risk assessment model which
demonstrated that eliminating dead and downer, 4D cattle, from the feed stream was a
disproportionately effective means of reducing the risk of re-infection "The disposition of c&e
that die on the farm would also have a substantial influence on the spread of BSE if the disease
were in traduced. " The base case scenario showed that the mean total number ofID.50~ (i.e.,
dosage sufficient to infect SO percent of exposed cattte) from healthy animals at slaughter
presented to the food/feed system was 1500, The mean total number of ID.50.s from adult cattle
Division of Dockets Management (HFA-305)
Page 3
9 December 2005
deadstockpresented to the feed system was 3 7,000.
deadstock).
This illustrates the risk of "40 cattle" (i.e.,
From the Harvard Risk Assessment, 2001, Appendix 3A Base Case and Harvard Risk
Assessment, 200 1 Executive Summary
Serologicals and companies like ours which supply components of drugs and biologicals have a
responsibility to the manufacturers of these products, the medical community and their patients
as well as regulatory agencies throughout the world to provide the safest products as possible.
Since there is no test for BSE in live cattle or for product, the regulatory agencies throughout the
world expect us to reduce or eliminate risk via suurcing criteria, These parameters may include
but not be limited to country of origin, herd of origin, age of the animal, etc. The United States
is no longer a country with negligible risk, hence individual animal criteria has become more
important. In fact other Centers of the FDA have stated that more attention should be given to
sourcing from herds likely to be a source of BSE free animals. The exemptions in the current
ban as well as in the newly proposed rule make this difficult if not impossible as there are still
legal avenues for ruminants to consume potentially contaminated ruminant protein. In addition,
the USDA still has not implemented a system of identification and traceability.
Serologicals urges agencies of the US government to work with academia and industry on
research in the following areas:
e Methods to inactivate TSEs agents which then may allow a product to be used and even
fed to animals without risk
l Alternative uses for animal byproducts which would maintain value
Serologicals will continue to work with the FDA and other government agencies to implement a
strong BSE risk control program, Serologicals would like to reiterate our opinion that for the
FDA to provide a more comprehensive and protective feed ban, specified risk materials (SRMs)
and deadstock must be removed from all animal feed and that legal exemptions which allow
ruminant protein to be fed back to ruminants (with the exception of milk) should be
discontinued. Thank you for the opportunity to submit these comments to the public record.
Respectfully,
SEROLOGICALS CORPORATION
James J. Kramer, Ph.D.
Vice President, Corporate Operations


http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000383-01-vol35.pdf


C 435 Government of Japan Vol #: 36


snip...


The Food safety risk assessment related to the import of beef and beef offal from the U.S.A. and Canada by the Food Safety Commission of Japan (FSC) was completed on December 8, 2005. REGARDING the feed ban, the following was noted as an ADDENDUM TO THE CONCLUSION ON THE RISK ASSESSMENT REPORT OF FSC:


"To prevent BSE exposure and amplification in U.S.A. and Canada, the use of SRM must be prohibited COMPLETELY. The ban must be applied not only to cattle feed but ALSO TO ALL OTHER ANIMAL FOOD/FEED that may cause cross-contamination."

snip...


http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-c000435-01-vol36.pdf



Subject: Re: McDonald's Corp. seven scientists and experts and a
pharmaceutical supplier Seriologicals Corp. U.S. NOT PROTECTED AGAINST MAD
COW DISEASE
Date: January 7, 2006 at 7:11 am PST

September 13,2004

USDA, FSTS

Docket Clerk

300 12* Street, SW

Room 102, Cotton Annex

Washington, DC 20250

04-021ANPR

04-021ANPR-70

Richard L. Crawford

Re: Docket No: 04-02 1 ANPR Federal Measures to Mitigate BSE Risks:
Considerations

for Further Action

Dear Sir or Madame:

On behalf of McDonald's Corporation, which operates more than 13,000
restaurants in

the United States, we appreciate the opportunity to submit comments to this
very

important Advance Notice of Proposed Rulemaking (ANPRM). 69 Fed. Reg. 42288
(July

14,2004).

In previous comments submitted to FSIS regarding the removal of SRI&,
McDonalds

fully supported this rule and its immediate implementation. The removal of
SRMs from

human food is the primary firewall to protect the US consumer from being
exposed to the

BSE agent. While we applaud the requirement for SRM removal, we feel that it
is

equally important for FSIS to insure that each slaughterplant which
processes cattle have

systems in place which prevent cross contamination between edible tissue and
SRMs.

This should include but not be limited to the use of separate equipment,
such as knives,

blades, etc. where appropriate. In addition, it is also important that
appropriate and

effective disinfection procedures for equipment used to handle SRMs be
developed and

approved for use.

It is our opinion that requiring SRM removal without a procedure to prevent
cross

contamination is inadequate as a protective public health measure. The TSE
agents

@ions) are sticky and highly resistant to disinfection. If SRMs such as
brain and spinal

cord are allowed to contact equipment and other surfaces such as deboning
tables which

then are used to handle and process edible tissue this could allow
contamination and

negates the intention of the ban. This is true not only in plants
slaughtering fed cattle

both under and over 30 months but also in plants slaughtering predominately
older cattle.

It is important that measure be taken to prevent cross contamination between
carcasses

and SRms in the cull plants. McDonalds requires their suppliers to prevent
cross

contamination and audits against certain measurable standards such as
requiring spinal

cord to bc removed on the kill floor. We would be willing to share these
standards with

FSIS as an example.

FSIS Docket No. 04-02 1 ANPR

dooqhl- =w c1qo -

McDonalds again recommends that dura (the covering around the brain and
spinal cord)

be added to the list of SRMs. While skull and vertebral column are included
as SRMs,

dura is not. If dura is not removed prior to processing on the fabrication
floor, it may

come loose and be incorporated into ground product. Bovine dura was never
tested for

infectivity. It was assumed that due to direct contact with spinal cord, it
may serve as a

vehicle to transmit disease. In addition, human dura has been the source of
human to

human transmission of Creutzfeldt-Jakob Disease (CJD). (personal
communication - Dr.

Danny Matthews, UK, VLA) Our ISAC committee recommended that McDonalds add

the removal of dura as a specification in the production of our product.

McDonalds urges the USDA to make the appropriate adjustments in the SRM ban
if new

scientific findings and/or the results of the increased surveillance warrant
a change.

In regards to imported meat products from other countries, McDonalds
suggests that no

SRM exemption be made for countries based on BSE risk. The long incubation
period

and limited surveillance in many countries can limit the ability to
accurately determine

risk. Also, the risk level of a country could potentially change over night
if the trading

patterns of a country changed. It seems logistically impossible to maintain
a system

which could continually monitor the world's trading patterns. In addition,
science has

not provided all of the answers in regards to the transmission of BSE.
Requiring SRMs

to be removed from imported products for human food is prudent. If the US
would wait

until disease is confirmed the exposure would already have occurred.

Thank you for the opportunity to comment on these very important issues.

Richard L. Crawford

Corporat,e Vice President, Government Relations

McDonalds Corporation

1 Kroc Drive

Oak Brook, Illinois 60523

FSIS Docket No. 04-021ANPR


http://www.fda.gov/ohrms/dockets/dailys/04/sep04/092104/04n-0264-c00140-vol2
2.pdf



2004N-0264 Federal Measures to Mitigate BSE Risks: Considerations for
Further Action

C 136 National Cattlemen's Beef Assn (NCBA) Vol #: 22

C 137 Public Citizen Vol #: 22

C 138 Center for Science in the Public Interest (CSPI) Vol #: 22

C 139 Humane Society of the United States (HSUS) Vol #: 22

C 140 McDonald's Corporation Vol #: 22

C 141 North American Natural Casing Assn (NANCA) Vol #: 22

C 142 National Renderers Assn Vol #: 22

C 143 G.A.O.B., Inc. Vol #: 22

C 144 Gelatin Manufacturers of Europe (GME) Vol #: 22

C 145 IBM Business Consulting Services Vol #: 22

C 146 L. Fischer Vol #: 22

C 147 C. Rothenfluch Vol #: 22

C 148 C. Addonizio Vol #: 22

C 149 M. Clifton Vol #: 22




http://www.fda.gov/ohrms/dockets/dailys/04/sep04/092104/092104.htm#04N0264



Dockets Entered on December 22, 2005
2005D-0330, Guidance for Industry and FDA Review Staff on Collection of
Platelets
by Automated ... EC 203, McDonald's Restaurants Corporation, Vol #:, 34 ...


http://www.fda.gov/ohrms/dockets/dailys/05/Dec05/122205/122205.htm


03-025IF 03-025IF-631 Linda A. Detwiler [PDF]
Page 1. 03-025IF 03-025IF-631 Linda A. Detwiler Page 2. Page 3. Page 4.
Page 5. Page 6. Page 7. Page 8. Page 9. Page 10. Page 11. Page 12.
http://www.fsis.usda.gov/OPPDE/Comments/03-025IF/03-025IF-631.pdf - Text Version

03-025IF 03-025IF-634 Linda A. Detwiler [PDF]
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Page 3. Page 4. Page 5. Page 6. Page 7. Page 8.
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[ More results from www.fsis.usda.gov/OPPDE/Comments/03-025IF/ ]

Page 1 of 17 9/13/2005 [PDF]
... 2005 6:17 PM To: [email protected]. Subject: [Docket
No. 03-025IFA]
FSIS Prohibition of the Use of Specified Risk Materials for Human Food ...
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf - Text Version

03-025IFA 03-025IFA-6 Jason Frost [PDF]
... Zealand Embassy COMMENTS ON FEDERAL REGISTER 9 CFR Parts 309 et al
[Docket No. 03-
025IF] Prohibition of the Use of Specified Risk Materials for Human Food and
...
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http://www.fsis.usda.gov/Search/Search_Results/Index.asp?q=03-025IF&mode=sim
ple&num=10&as_occt=any&restrict=FSIS_DOCKET_COMMENTS



In its opinion of 7-8 December 2000 (EC 2000), the SSC ... [PDF]
Page 1. Linda A. Detwiler, DVM 225 Hwy 35 Red Bank, New Jersey 07701 Phone:
732-741-2290
Cell: 732-580-9391 Fax: 732-741-7751 June 22, 2005 FSIS Docket Clerk US ...
http://www.fsis.usda.gov/OPPDE/Comments/03-025IF/03-025IF-589.pdf



http://www.fsis.usda.gov/OPPDE/Comments/03-025IF/03-025IF-589.pdf



Page 1 of 17 9/13/2005 [PDF]
... Page 1 of 17 From: Terry S. Singeltary Sr. [[email protected]] Sent:
Thursday,
September 08, 2005 6:17 PM To: [email protected].
Subject ...
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf



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03-025IF 03-025IF-618 Richard L. Crawford [PDF]
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03-038IF 03-038IF-15 Richard L. Crawford [PDF]
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http://www.fsis.usda.gov/OPPDE/Comments/03-038IF/03-038IF-15.pdf



http://www.fsis.usda.gov/OPPDE/Comments/03-025IF/03-025IF-634.pdf



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