To: BSE-L@uni-karlsruhe.de
######## Bovine Spongiform Encephalopathy #########
Greetings List Members,
going over a few items of interest and thought
of the infamous sporadic CJD one-in-a-million
BSeee;
Comparability of Cause of Death Between ICD–9
and ICD–10: Preliminary Estimates
by Robert N. Anderson, Ph.D.; Arialdi M. Miniño, M.P.H.; Donna L.
Hoyert, Ph.D.; and Harry M. Rosenberg, Ph.D.
Volume 49, Number 2 May 18, 2001
Alzheimer’s disease
The comparability ratio for Alzheimer’s disease (113-list number
052) is 1.5536, which indicates a 55 percent increase in Alzheimer’s
disease deaths when classified by ICD–10. In absolute terms, over
10,000 more deaths were classified to Alzheimer’s disease in ICD–10
than in ICD–9. Nearly all of this increase (about 95 percent) comes
from deaths classified in ICD–9 as Presenile dementia (290.1). In
ICD–9, a definitive diagnosis was required for classification as
Alzheimer’s disease. Terms such as ‘‘Alzheimer’s-type dementia’’ or
‘‘Alzheimer’s dementia’’ were classified as Presenile dementia rather
than Alzheimer’s disease. In addition, in ICD–9, if an unspecified
chronic organic psychotic condition (294.9) is mentioned with Alzheimer’s
disease, the two conditions form a linkage and are coded to
290.1. Under ICD–10, this linkage does not exist, strictures regarding
definitive diagnosis are relaxed, and, thus any mention of Alzheimer’s
is classified as Alzheimer’s disease (G30). This involves the
reclassification
of nearly all cases of Presenile dementia to Alzheimer’s
disease.
The application of the comparability ratio presented for Alzheimer’s
disease to years later than 1996 may be problematic (i.e., it may
substantially underestimate the increase in Alzheimer’s due to
implementation
of the ICD–10 classification). Increases in the reporting of
Alzheimer’s-type dementia as a cause of death have occurred since
1996, resulting in substantial increases in Presenile dementia (290.1)
from 1996 to 1998. Table E shows the trend in ICD–9-classified Alzheimer’s
disease and Presenile dementia deaths from 1996 to 1998. The
number of Alzheimer’s disease deaths increased by about 1,000 deaths
between 1996 and 1997; between 1997 and 1998, the increase was
only about 300 deaths. In contrast, the increase in Presenile dementia
was more substantial, about 2,000 deaths each year. Thus, the comparability
ratio based on 1998 data is probably at least 1.69 (approximating
the ICD–10-classified Alzheimer’s disease deaths by adding the
Alzheimer’s disease and Presenile dementia deaths). Assuming proportionately
similar increases in the ICD–9 classification of Alzheimer’s
disease and Presenile dementia from 1998 to 1999, the comparability
ratio based on 1999 data could be as high as 1.8 or 1.9.
Table E. Number of deaths due to Alzheimer’s disease
and Presenile dementia: United States, 1996–98
Cause of death (ICD–9 code)1
Year
1996 1997 1998
Alzheimer’s disease. . . . . . . (331.0) 21,397 22,475 22,725
Presenile dementia . . . . . . . (290.1) 11,877 13,622 15,672
http://www.cdc.gov/nchs/data/nvsr/nvsr49/nvsr49_02.pdf
Item Code:
16
Default Label:
Alzheimer's disease
------------------------------------------------------------------------
Notes:
Alzheimer's disease.
Beginning with data year 1979, WHO introduced a separate category for
Alzheimer's disease, which is believed under reported.
ICD-9 code: 331.0
http://209.217.72.34/aging/eng/TableViewer/wdsdim/itemSummaryp.asp
Quality of reporting and processing cause of death
One index of the quality of reporting causes of death is the
proportion of death certificates coded to Chapter XVIII; Symptoms,
signs and abnormal clinical and laboratory findings, not elsewhere
classified (ICD–10 codes R00–R99). Although deaths occur for which
the underlying causes are impossible to determine, this proportion
indicates the care and consideration given to the cause-of-death
statement by the medical certifier. This proportion also may be used
as a rough measure of the specificity of the medical diagnoses made
by the certifier in various areas. The percent of all reported deaths in
the United States assigned to Symptoms, signs and abnormal clinical
and laboratory findings, not elsewhere classified, was 1.34 percent,
about the same as in 2000 (1.33 percent), but considerably higher
than in 1999 (1.12 percent). From 1990 through 1999, the percent of
deaths from this cause for all ages combined generally was fairly
stable, between 1.08 and 1.18 percent.
snip...
Rare causes of death
Selected causes of death considered to be of public health
concern are routinely confirmed by the States according to agreed
upon procedures between the State vital statistics programs and
NCHS. These causes, termed ‘‘Infrequent and rare causes of death,’’
are listed in the NCHS instruction manuals Parts 2a, 11, and 20
(33,55,56).
For data year 2001, complete confirmation of deaths from infrequent
and rare causes were not provided by the District of Columbia
and the following States: California, Illinois, Indiana, Kansas, Kentucky,
Maine, Minnesota, Montana, New Jersey, New York, North Dakota,
Ohio, Oklahoma, Pennsylvania, and Rhode Island.
snip...
Cause-of-death classification
The mortality statistics presented in this report were compiled in
accordance with World Health Organization (WHO) regulations, which
specify that member nations classify and code causes of death in
accordance with the current revision of the International Classification
of Diseases (ICD). The ICD provides the basic guidance used in
virtually all countries to code and classify causes of death. Effective
with deaths occurring in 1999, the United States began using the
Tenth Revision of this classification (ICD–10) (7). For earlier years
causes of death were classified according to the revisions then in
use—1979–98, Ninth Revision; 1968–78, Eighth Revision, adapted
for use in the United States; 1958–67, Seventh Revision; and
1949–57, Sixth Revision.
Changes in classification of causes of death due to these revisions
may result in discontinuities in cause-of-death trends. Consequently,
cause-of-death comparisons among revisions require consideration of
comparability ratios and, where available, estimates of their standard
Nature and sources of data
Data in this report are based on information from all death
certificates filed in the 50 States and the District of Columbia and are
processed by the Centers for Disease Control and Prevention’s
National Center for Health Statistics (NCHS). Data for 2001 are
based on records of deaths that occurred during 2001 and were
received as of October 24, 2002. The U.S. Standard Certificate of
Death—which is used as a model by the States—was last revised in
1989; for additional details see the 1989 revision of the U.S. standard
certificates and reports (28) and Technical Appendix of Vital Statistics
of the United States, 1989, Volume II, Mortality, part A (29). Data for
Puerto Rico, the Virgin Islands, Guam, American Samoa, and the
Northern Marianas are included in tables showing data by State, but
are not included in U.S. totals.
Mortality statistics are based on information coded by the States
and provided to the NCHS through the Vital Statistics Cooperative
Program (VSCP) and from copies of the original certificates received
by NCHS from the State registration offices. In 2001 all the States and
the District of Columbia participated in this program and submitted part
or all of the mortality data for 2001 in electronic data files to NCHS.
All States provided precoded medical (cause-of-death) data to NCHS
except Illinois, Kentucky, New Jersey, Ohio, and West Virginia, and the
District of Columbia. For 2001 all States submitted precoded demographic
data for all deaths.
Data for the entire United States refer to events occurring within
the United States. Data shown for geographic areas are by place of
residence. Beginning with 1970 mortality statistics for the United States
exclude deaths of nonresidents of the United States. All data exclude
fetal deaths.
Mortality statistics for Puerto Rico, Virgin Islands, American
Samoa, and Northern Marianas exclude deaths of nonresidents of
Puerto Rico, Virgin Islands, American Samoa, and Northern Marianas,
respectively. For Guam, however, mortality statistics exclude deaths
that occurred to a resident of any place other than Guam or the United
States.
Cause-of-death classification
The mortality statistics presented in this report were compiled in
accordance with World Health Organization (WHO) regulations, which
specify that member nations classify and code causes of death in
accordance with the current revision of the International Classification
of Diseases (ICD). The ICD provides the basic guidance used in
virtually all countries to code and classify causes of death. Effective
with deaths occurring in 1999, the United States began using the
Tenth Revision of this classification (ICD–10) (7). For earlier years
causes of death were classified according to the revisions then in
use—1979–98, Ninth Revision; 1968–78, Eighth Revision, adapted
for use in the United States; 1958–67, Seventh Revision; and
errors. Comparability ratios between the Ninth and Tenth Revisions,
between the Eighth and Ninth Revisions, between the Seventh and
Eighth Revisions, and between the Sixth and Seventh Revisions may
be found in other NCHS reports (20,30–32).
The ICD not only details disease classification but also provides
definitions, tabulation lists, the format of the death certificate, and the
rules for coding cause of death. Cause-of-death data presented in this
publication were coded by procedures outlined in annual issues of the
NCHS Instruction Manual (33,34). The manual includes rules for
selecting the underlying cause of death for tabulation purposes,
definitions,
tabulation lists, and regulations on the use of the ICD.
Before data for 1968, mortality medical data were based on
manual coding of an underlying cause of death for each certificate in
accordance with WHO rules. Effective with data year 1968, NCHS
converted to computerized coding of the underlying cause and manual
coding of all causes (multiple causes) on the death certificate. In this
system, called ‘‘Automated Classification of Medical Entities’’ (ACME)
(35), multiple cause codes serve as inputs to the computer software
that employs WHO rules to select the underlying cause. All cause-ofdeath
data in this report are coded using ACME.
The ACME system is used to select the underlying cause of death
for all death certificates in the United States. In addition, NCHS has
developed two computer systems as inputs to ACME. Beginning with
1990 data, the Mortality Medical Indexing, Classification, and Retrieval
system (MICAR) (36,37) was introduced to automate coding multiple
causes of death. In addition, MICAR provides more detailed information
on the conditions reported on death certificates than is available
through the ICD code structure. Then, beginning with data year 1993,
SuperMICAR, an enhancement of the MICAR system, was introduced.
SuperMICAR allows for literal entry of the multiple cause-of-death text
as reported by the certifier. This information is then automatically
processed by the MICAR and ACME computer systems. Records that
cannot be automatically processed by MICAR or SuperMICAR are
manually multiple-cause coded and then further processed through
ACME.
For 2001 approximately 61 percent of the Nation’s death records
were multiple-cause coded using SuperMICAR and 39 percent using
MICAR only. This represents data from 37 States, New York City, and
the District of Columbia that were coded by SuperMICAR and data from
13 States that were coded by MICAR.
In this report tabulations of cause-of-death statistics are based
solely on the underlying cause of death. The underlying cause is
defined by WHO as ‘‘the disease or injury which initiated the train of
events leading directly to death, or the circumstances of the accident
or violence which produced the fatal injury’’ (7). It is selected from the
conditions entered by the physician in the cause-of-death section of the
death certificate. When more than one cause or condition is entered
by the physician, the underlying cause is determined by the sequence
of conditions on the certificate, provisions of the ICD, and associated
selection rules and modifications. Generally, more medical information
is reported on death certificates than is directly reflected in the
underlying
cause of death. This is captured in NCHS multiple cause-of-death
statistics (38–40).
snip...
http://www.cdc.gov/nchs/data/nvsr/nvsr52/nvsr52_03.pdf
Mortality Data from the National Vital Statistics System
http://www.cdc.gov/nchs/about/major/dvs/mortdata.htm
US STANDARD CERTIFICATE OF DEATH
snip...
CHANGES TO CAUSE OF DEATH
additional medical information or autopsy findings become available that
would change the cause of death originally reported, the original death
certificate should be amended by the certifying physician by immediately
reporting the revised cause of death to the State Vital Records Office.
snip...
When processes such as the following are reported, additional
information about the etiology should be reported:
[PLEASE NOTE OUT OF ALL THE CONDITIONS LISTED, NOT
A WORD ABOUT CJD...TSS]
http://www.cdc.gov/nchs/data/dvs/DEATH11-03final-ACC.pdf
THIS is a dandy one;
Items 37&45. For States with laws allowing unconventional types of
people certify cause of death ONLY, we have added an additional category
Other Individual Legally Allowed to Certify, an additional literal field
for capturing the other types of individuals, and suggested a
certification statement for these types....
SO, they now have a special classification for bozo's that are not certified
to read over these coding statistics, and CJD still one-in-a-million? RIGHT!
http://www.cdc.gov/nchs/data/dvs/changestodspecs82302.doc
One reason for this was the _inaccuracy_ in coding of cases correctly
certified as CJD Coding is carried out by staff who are not medically
qualified
and it is not surprising that coding errors occur in the processing of
large
numbers of certificates. In 1982, 12,000 certificates per week were
processed at
the office of population censuses and surveys bu 15 coders and 6
checkers (Alderson et
al., 1983). The occurrence of both inter- and intra-observer coding errors
has been described (Curb et al., 1983) and the _inaccuracies_ of BOTH
certification and coding discovered in this study _support_ the
introduction of a more
accurate system of death certificates and a more detailed and specific
coding system...
snip...
http://www.bseinquiry.gov.uk/files/mb/m26/tab01.pdf
BESIDES the studies below on misdiagnosis of CJD as Alzheimer's
(DUKE, PA, and YALE from 3 to 13 % misdiagnosed, please
see my BSE-L submission of Jan. 14, 2993 below, but first,
i have failed to get this Mexican study online, so here it is;
Greetings again,
This study i have failed to get online ;
ABSTRACT
Clinico-Pathological Correlation in Dementias
F. Teixeira, El Alonso, V. Romero, A. Ortiz, C. Martinez, E. Otero
Departments of Experimental Neuropathology and Genetics, and the
Division of Psychology and Neurology, National Institute of Neurology
Neurosurgery, Mexico City, Mexico
Sumitted: February 22, 1994
Accepted: February 9, 1995
The object of this study is to investigate whether or not there are
clinical signs
and symptoms in patients with dementia that, by themselves or jointly,
can be
associated with the pathological diagnosis of Alzheimer's disease. Twelve
patients with dementia were studied, in whom the clinical diagnosis of
Alzheimer's disease was made according to established criteria. A sample
of leptomeninges, cortex and subcortical white matter was obtained from
each patient and was processed for light and electron microscopy. In the
cases
in whom neuritic plaques and neurofibrilary tangles were present,
pathological
changes were quantified. The diagnosis of Alzheimer's disease was confirmed
in 5 cases, wheras in 3 patients SPONGIFORM ENCEPHALOPATHY
was present. In the remaining patients, the number of neuritic plaques
was within
normal limits for the age of the subjects. Comparison of the data in
Alzheimer
(n=5) and non-Alzheimer (n=7) groups showed an increased, statistically
significant incidence of acalculia, abnormalities of judgement,
impairment of
abstraction and primitive reflexes in the former. Although good fitting
models
were obtained, none achieved perfect discrimination. The model that included
alterations of judgement and acalculia gave the best fit...
snip...
DISCUSSION
The rates of accuracy of the clinical diagnosis of Alzheimer's
disease in several clinico-patholigical studies range from
43% to 87% (Joachim et al 1988; Mosla et al 1985; Muller and
Schwartz 1978; Nott and Fleminger 1975; Sulkava et al 1983;
Todorov et al 1975; Wade et al 1987). It should be interesting,
therefore, if selected clinical data could help to reach this
diagnosis without the aid of a brain biopsy.
The results of this study show a very significant association of
Alzheimer's disease with the following variables primitive
reflexes, impairment of abstraction, changes in judgment
and acalculie. In studying the joint effect of variables,
it was seen that alterations of judgment and acal-
culia produced the best fit.
The sample in this study may be considered small for the
purpose of selecting a set of signs and symptoms that can
characterize Alzheimer's disease clinically. However, it is
not an easy task to obtain the permission to perform a brain
biopsy which is of no benefit for the patient when the relative
is informed of the risks involved.
The definite diagnosis of Alzheimer's disease depends on
the microscopical examination of brain tissue, either by
autopsy or biopsy. In the USA, the Alzheimer Disease
Research Center of the University of Pittsburgh has launched
a public campaign to encourage relatives of demented pa-
tients to request a postmortem examination of the brain
(Boiler et al 1989). However, in Mexico, a similar campaign
has enjoyed little success so far for several reasons. The
patient who suffers from Alzheimer's disease usually dies at
home. The relatives, who are already exhausted by the de-
mands of caretaking, obtain a death certificate from the
family physician, and proceed quickly to the funeral rites.
The few families who do request an autopsy are almost
invariably denied admission to the hospital where the patient
had been admitted because cadavers without a death certifi-
cate must be sent to the police department for autopsy. Many
Patients die in small towns or villages where there are no
pathologist, let alone neuropathologists. Therefore, brain
biopsy remains the only possibility for confirming the clinical
diagnosis. It is true that there is no benefit derived by the
Patient from this procedure and that he or she faces surgical
and anesthetic risks. In contrast, brain biopsy allows: 1. the
development of new diagnostic procedures that might, in the
future, replace it; 2. adequate genetic counseling in cases
with an autosomal dominant pattern of inheritance, so that
family members can take part in studies at the molecular
biology level; and 3. the performance of therapeutic trials and
of epidemiological surveys in Mexico.
Familiar aggregation has been demonstrated in 40% of
cases of Alzheimer's disease. In 15% of these cases, the
pattern of inheritance was autosomal dominant (Heston el al
1981). Patient number nine's family is an example of the
latter, and showed an early age of onset.
Vacuolar change, similar to that present in jakob-
Creutzfeldt disease, has been described in brains of patients
with Alzheimer's disease, especially al the medial temporal
isocortex, where it has a high, statistically significant asso-
ciation with the presence of large numbers of neurofibrillary
tangles and argyrophllic plaques (Smith et al 1987) This
study considered the possibility that cases 5 to 7, diagnosed
as Jakob-Creutzfeldt disease, could be, in fact, Alzheimer
cases with this peculiar vacuolar change. A good method for
separating the two entities would be the use of antibodies
against prion (Pr-P) proteins (Tateishi et a] 1988), which
were, unfortunately, not available to the authors. However,
none of these cases showed positivity for A4 protein. neither
had one single argyrophilic plaque or tangle. Moreover, the
biopsies were taken from the frontal regions, which are
reported to be free of involvement in instances of
Alzheimer's disease with vaeuolar changes (Smith et al
1987).
Although the diagnosis of probable Alzheimer's disease
was made in all of the patients in this study, according to the
criteria established by McKhann et al (1984), this diagnosis
was confirmed in only 47.1% of them, This low rate might
be the result of several factors. The National Institute of
Neurology and Neurosurgery in Mexico City is an institution
that concentrates especially on difficult or unusual cases that
are referred from all over the country. Therefore, it received
a biased sample that included as many as 3 cases of spongi-
form encephalopathy. In addition, it is important to remember
that a small. 1 cubic centimeter sample of cortex and white
matter may not be representative of the extent of the damage
in other areas of the brain, and so, correlates poorly with the
clinical picture. This illustration is particularly true of cases
1 to 4. which did not fit into any of the pathological entities
that manifest clinically as dementia. To understand more
clearly the relation between damage and clinical impairment,
further prospective studies using autopsy material are needed...
END
=====================================
Subject: CJD, Alzheimer's, one-in-a-million and the USA CJD FOUNDATION
CJD Questionnaire (if that is what you want to call it)
Date: Tue, 14 Jan 2003 16:34:10 -0600
From: "Terry S. Singeltary Sr."
Reply-To: BSE-L
Greetings list members,
something else i am curious about, i read here where
it states;
> However, the crux of the comparison rests
> squarely on results of attempts to transmit AD
> to experimental animals, and these results have
> not as yet validated a common etiology.
now what about these findings;
IN STRICT CONFIDENCE
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
so why not have any of these type studies started?
seems from the studies below, this warrants further
investigation asap...
1: Ann N Y Acad Sci 1982;396:131-43
Alzheimer's disease and transmissible virus dementia
(Creutzfeldt-Jakob disease).
Brown P, Salazar AM, Gibbs CJ Jr, Gajdusek DC.
Ample justification exists on clinical, pathologic, and biologic
grounds for considering a similar pathogenesis for AD and the spongiform
virus encephalopathies. However, the crux of the comparison rests
squarely on results of attempts to transmit AD to experimental animals,
and these results have not as yet validated a common etiology.
Investigations of the biologic similarities between AD and the
spongiform virus encephalopathies proceed in several laboratories, and
our own observation of inoculated animals will be continued in the hope
that incubation periods for AD may be even longer than those of CJD.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6758661&dopt=Abstract
1: Neurology 1980 Sep;30(9):945-50
Evidence for and against the transmissibility of Alzheimer disease.
Goudsmit J, Morrow CH, Asher DM, Yanagihara RT, Masters CL, Gibbs
CJ Jr, Gajdusek DC.
Nonhuman primates were inoculated intracerebrally with brain tissue
from 52 patients with confirmed Alzheimer disease (AD) in order to
investigate the possibility of an infectious etiology. Animals
inoculated with brain tissue from two patients with familial AD
developed a spongiform encephalopathy that was indistinguishable from
Creutzfeldt-Jakob disease (CJD). Seventeen other cases of AD on test for
more than 50 months failed to produce similar changes, and 33 cases have
not been incubating for a sufficient period of time to ascertain the
presence of a transmissible agent. The initial transmission of
spongiform encephalopathy with brain tissue from the two familial cases
of AD has not been reproduced and the association between AD and an
infectious agent has not yet been demonstrated with any reasonable
degree of certainty. The frequent overlap of clinical symptoms of AD and
CJD, and the occurrence of cases of CJD and AD in the same families
indicate the need for continuing research on the relationship between
the two diseases.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6775247&dopt=Abstract
1: Neurology 1990 Feb;40(2):226-8
Coexistence of Creutzfeldt-Jakob disease and Alzheimer's disease in
the same patient.
Brown P, Jannotta F, Gibbs CJ Jr, Baron H, Guiroy DC, Gajdusek DC.
Laboratory of CNS Studies, NINDS, National Institutes of Health,
Bethesda, MD 20892.
We report the case of a 73-year-old patient in whom a diagnosis of
Creutzfeldt-Jakob disease, suggested by the clinical course, was
verified by the neuropathologic finding of widespread spongiform change
and astrogliosis, the presence of proteinase-resistant protein in brain
extracts, and the experimental transmission of spongiform encephalopathy
to primates inoculated with brain tissue. However, neuropathologic
examination also revealed a profusion of senile and neuritic plaques and
neurofibrillary tangles that reacted with antibody to the amyloid
beta-protein characteristic of Alzheimer's disease, but not with
antibody to the scrapie amyloid protein characteristic of
Creutzfeldt-Jakob disease.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2405293&dopt=Abstract
1: Eur J Epidemiol 1986 Dec;2(4):252-64
Familial Creutzfeldt-Jakob disease in France: epidemiological
implications.
Baron H, Cathala F, Brown P, Chatelain J, Gajdusek DC.
Of 329 patients dying of Creutzfeldt-Jakob disease (CJD) in
continental France between 1968 and 1982, 19 (6%) were familial cases.
Genealogical investigation permitted the identification of 19 additional
cases, bringing the total number of familial CJD cases reported here to
38. There are 6 definitely affected families, yielding an average of 6.3
cases per family. Mediterranean Jews account for one-third of all the
cases, with Tunisian Jews constituting two-thirds of this ethnic group.
Males and females are equally affected. The overall rate of occurrence
(47.3%) is consistent with autosomal dominant transmission, but wide
variations in individual pedigrees (26.7%-80%) leave this hypothesis
open to scrutiny. Age at death is 10 to 15 years lower in familial than
in sporadic CJD, suggesting the possible inheritance of "short
incubation" genes in certain CJD families. Disease duration is longer in
familial than in sporadic CJD, but this could be the effect of
ascertainment bias. There is no evidence for maternal lineage. While
members of a given family tend to die within the same age bracket, our
data fail to discriminate between vertical transmission and common
source exposure as hypothetical transmission mechanisms within affected
families. CJD occurrence in a woman related by marriage to an unaffected
branch of a CJD family, but who was raised in early childhood by the
affected branch, argues in favor of horizontal transmission early in
life. Analysis of death intervals and geographic/temporal separations
suggests minimal incubation periods of up to 43 years. A family
combining clinico-pathological features of CJD and the
Gerstmann-Straussler syndrome (GSS) indicates a nosological relationship
between the two. The "genetic susceptibility" of members of CJD-affected
families may be due to accelerated derepression of normally repressed
host genes, coding for abnormal amyloid-type proteins. Accumulation of
these proteins may play an important role in the pathogenesis of CJD and
scrapie, and constitute a common pathogenetic mechanism in several
neurological diseases, including Alzheimer's disease (AD) and senile
dementia of the Alzheimer type (SDAT).
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3542553&dopt=Abstract
1: Ann N Y Acad Sci 1982;396:131-43
Alzheimer's disease and transmissible virus dementia
(Creutzfeldt-Jakob disease).
Brown P, Salazar AM, Gibbs CJ Jr, Gajdusek DC.
Ample justification exists on clinical, pathologic, and biologic
grounds for considering a similar pathogenesis for AD and the spongiform
virus encephalopathies. However, the crux of the comparison rests
squarely on results of attempts to transmit AD to experimental animals,
and these results have not as yet validated a common etiology.
Investigations of the biologic similarities between AD and the
spongiform virus encephalopathies proceed in several laboratories, and
our own observation of inoculated animals will be continued in the hope
that incubation periods for AD may be even longer than those of CJD.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6758661&dopt=Abstract
Greetings again list members,
i believe if the USA had any _real_ CJD surveillance, except the
token prion unit at Case Western, with no disrespect to Dr.
Gambetti, but he is working either directly or indirectly
for the CDC/NIH, if you look at it from a funding/grants
prospect. plus, his prospects of finding any CJD with a CJD
Questionnaire that ask no questions as to route/source,
and CJD/TSEs _not_ reportable nationally, i just do not understand
how any surveillance can be done this way. it kinda reminds
me of the extensive 13 year old USA BSE Surveillance program.
could someone please explain to me, how anyone could figure out the
route and source of the TSE agent with a questionnaire like (see below),
especially since the new findings by Collinge et al, that BSE
transmission to the 129-methionine genotype can lead to an alternate
phenotype which is indistinguishable from type 2 PrPSc, the commonest
sporadic CJD. would these new findings even further warrant immediate
actions as to making CJD reportable nationally and having a CJD
questionnaire that ask _real_ questions pertaining to route/source?
seems to me, with a CJD Questionnaire such as this, and the questions
they ask, the only thing they want to find out is, how it was diagnosed,
probably to just find a flaw in any confirmed cases, to negate the
confirmation, to hold at one-in-a-million. OR, it could be part of the
Presidents new anti-terrorist anit-public information program (re-FOIA).
i am just thinking out loud here, but why no questions pertaining to
route and source, is this not a very important factor?
CJD FOUNDATION QUESTIONNAIRE
REPORT FOR DATA BASE OF PATIENTS WITH CREUTZFELDT--JAKOB DISEASE (CJD)
OR OTHER TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (TSE's)
Name of Patient*:
(not required; if provided, must be with express consent of family member)
Date form filled out: / / (mm/dd/yy)
Person filling out form:
Relationship of person filling out form to patient:
Location where patient died: State: County: City:
Location where patient resided: State: County: City:
Sex of patient: male female unknown
Race of patient: white African-American -- Asian/Pacific Islander
American-Indian/Alaskan Native Other (please identify:
Unknown
Patient's date of birth: (mm/dd/yy)
Age of patient at onset of symptoms:
Date of patient's initial symptoms: (mm/dd/yy)
Age of patient at time of death:
Patient's date of death: (mm/dd/yy)
Duration of illness: months
Was this case referred to the National Prion Disease Pathology
Surveillance Center at Case Western Reserve University in Cleveland,
Ohio? yes no unknown
If yes, by whom was this case referred?
Pathologist -- Neuropathologist -- Neurologist
Other Physician (please identify which kind:
Unknown
Who made initial diagnosis of CJD or other TSE?
Pathologist - Neuropathologist - Neurologist
Other Physician (please identify which kind: )
Unknown
Please describe the clinical neurological presentation of the illness
(list the symptoms or signs):
at onset of the illness:
during the course of illness:
Was an EEG (electroencephalogram) performed? yes -- no -- unknown
If yes,
how long after onset was the EEG performed?
how many times was the EEG performed?
can you indicate the results?
- slow periodic sharp waves (PSW)
- unilateral periodic sharp waves (LSW)
- not reported
- other
Was the cerebrospinal fluid tested for the 14-3-3 protein? yes - no -
unknown
If yes, what was the result? positive - negative - unknown
Was a brain biopsy performed? - yes - no - unknown
If yes, what was the result?_____positive for____
______negative for CJD and other TSE's
______unknown
Was an autopsy performed? yes - no - unknown
If yes, what was the result? _____positive for____
______negative for CJD and other TSE's
______unknown
Was the neuropathology of this case consistent with new variant CJD?
yes - no - unknown
What was the final diagnosis of this case?
___CJD, probably sporadic
___Familial (hereditary) CJD
___Iatrogenic (by infection) CJD; please specify_______________
___Gerstmann-Strausster-Scheinker Syndrome (GSS)
___Fatal Familial Insomnia (FFI)
___Other
___Unknown
* I hereby give consent to the Creutzfeldt-Jakob Disease Foundation,
Inc. to use the above information, including name of patient if
supplied, in connection with activities to promote the research,
education and awareness of Creutzfeldt-Jakob Disease and related
transmissible spongiform encephalopathies.
-4-
END
====================================================
4.5 MILLION DEMENTED ALZHEIMER'S, HOW MANY ARE CJD/TSEs?
how can on-in-a-million be accurate when CJD is not reportable,
when the elderly rarely if ever get autopsied?
Subject: Re: Hello Dr. Manuelidis
Date: Fri, 22 Dec 2000 17:47:09 -0500
From: laura manuelidis
Reply-To: laura.manuelidis@yale.edu
Organization: Yale Medical School
To: "Terry S. Singeltary Sr."
References: <39B5561A.87B84A28@wt.net> <39B64574.A4835745@yale.edu>
<39B680D8.3872535B@wt.net> <39B66EF1.4CE25685@yale.edu>
<39BBB812.425109F@wt.net> <39BE84CB.D7C0C16B@yale.edu>
<3A3BA197.7F60D376@wt.net>
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
also;
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
(A4) amyloid in primates by injection of Alzheimer’s disease brain
homogenate. Mol. Neurobiol (1994) 8: 25-39.) (J/MN/8/25)
re-alzheimer's disease
(note a substantial increase on a yearly basis)
http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
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
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)
also;
snip...
Comment
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 Swiss National Science Foundation.
http://jama.ama-assn.org/issues/v283n13/ffull/jlt0405-5.html
my point being;
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
TSS
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Terry S. Singeltary Neurology Online, 27 Jan 2003 [Full text]
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States 26 March 2003
Next Post-Publication Peer Review Top Terry S. Singeltary,
retired (medically)
CJD WATCH
Send Post-Publication Peer Review to journal:
Re: RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to
comment on the CDC's attempts to monitor the occurrence of emerging
forms of CJD. Asante, Collinge et al [1] have reported that BSE
transmission to the 129-methionine genotype can lead to an alternate
phenotype that is indistinguishable from type 2 PrPSc, the commonest
sporadic CJD. However, CJD and all human TSEs are not reportable
nationally. CJD and all human TSEs must be made reportable in every
state and internationally. I hope that the CDC does not continue to
expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in
the USA in both animal and man. CWD in deer/elk is spreading rapidly and
CWD does transmit to mink, ferret, cattle, and squirrel monkey by
intracerebral inoculation. With the known incubation periods in other
TSEs, oral transmission studies of CWD may take much longer. Every
victim/family of CJD/TSEs should be asked about route and source of this
agent. To prolong this will only spread the agent and needlessly expose
others. In light of the findings of Asante and Collinge et al, there
should be drastic measures to safeguard the medical and surgical arena
from sporadic CJDs and all human TSEs. I only ponder how many sporadic
CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
Reply to Singletary 26 March 2003
Previous Post-Publication Peer Review Top Ryan Maddox, MPH
CDC, Division of Viral and Rickettsial Diseases,
Ermias D. Belay, MD, Lawrence B. Schonberger, MD
Send Post-Publication Peer Review to journal:
Re: Reply to Singletary
Email Ryan Maddox, MPH, et al.:
zzp7@cdc.gov
Mr. Singletary raises several issues related to current Creutzfeldt-
Jakob disease (CJD) surveillance activities. Although CJD is not a
notifiable disease in most states, its unique characteristics,
particularly its invariably fatal outcome within usually a year of
onset, make routine mortality surveillance a useful surrogate for
ongoing CJD surveillance.1 In addition, because CJD is least accurately
diagnosed early in the course of illness, notifiable-disease
surveillance could be less accurate than, if not duplicative of, current
mortality surveillance.1 However, in states where making CJD officially
notifiable would meaningfully facilitate the collection of data to
monitor for variant CJD (vCJD) or other emerging prion diseases, CDC
encourages the designation of CJD as a notifiable disease.1 Moreover,
CDC encourages physicians to report any diagnosed or suspected CJD cases
that may be of special public health importance (e.g., vCJD, iatrogenic
CJD, unusual CJD clusters). As noted in our article, strong evidence is
lacking for a causal link between chronic wasting disease (CWD) of deer
and elk and human disease,2 but only limited data seeking such evidence
exist. Overall, the previously published case-control studies that have
evaluated environmental sources of infection for sporadic CJD have not
consistently identified strong evidence for a common risk factor.3
However, the power of a case-control study to detect a rare cause of CJD
is limited, particularly given the relatively small number of subjects
generally involved and its long incubation period, which may last for
decades. Because only a very small proportion of the US population has
been exposed to CWD, a targeted surveillance and investigation of
unusual cases or case clusters of prion diseases among persons at
increased risk of exposure to CWD is a more efficient approach to
detecting the possible transmission of CWD to humans. In collaboration
with appropriate local and state health departments and the National
Prion Disease Pathology Surveillance Center, CDC is facilitating or
conducting such surveillance and case- investigations, including related
laboratory studies to characterize CJD and CWD prions. Mr. Singletary
also expresses concern over a recent publication by Asante and
colleagues indicating the possibility that some sporadic CJD cases may
be attributable to bovine spongiform encephalopathy (BSE).4 The authors
reported that transgenic mice expressing human prion protein homozygous
for methionine at codon 129, when inoculated with BSE prions, developed
a molecular phenotype consistent with a subtype of sporadic CJD.
Although the authors implied that BSE might cause a sporadic CJD-like
illness among persons homozygous for methionine, the results of their
research with mice do not necessarily directly apply to the transmission
of BSE to humans. If BSE causes a sporadic CJD-like illness in humans,
an increase in sporadic CJD cases would be expected to first occur in
the United Kingdom, where the vast majority of vCJD cases have been
reported. In the United Kingdom during 1997 through 2002, however, the
overall average annual mortality rate for sporadic CJD was not elevated;
it was about 1 case per million population per year. In addition, during
this most recent 6-year period following the first published description
of vCJD in 1996, there was no increasing trend in the reported annual
number of UK sporadic CJD deaths.3, 5 Furthermore, surveillance in the
UK has shown no increase in the proportion of sporadic CJD cases that
are homozygous for methionine (Will RG, National CJD Surveillance Unit,
United Kingdom, 2003; personal communication).
References
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Diagnosis and
reporting of Creutzfeldt-Jakob disease. JAMA 2001;285:733-4.
2. Belay
ED, Maddox RA, Gambetti P, Schonberger LB. Monitoring the occurrence of
emerging forms of Creutzfeldt-Jakob disease in the United States.
Neurology 2003;60:176-181.
3. Belay ED. Transmissible spongiform
encephalopathies in humans. Annu Rev Microbiol 1999;53:283-314.
4.
Asante EA, Linehan JM, Desbruslais M, et al. BSE prions propagate as
either variant CJD-like or sporadic CJD-like prion strains in transgenic
mice expressing human prion protein. EMBO J 2002;21:6358-66.
5. The
UK Creutzfeldt-Jakob Disease Surveillance Unit. CJD statistics.
Available at: http://www.cjd.ed.ac.uk/figures.htm. Accessed February 18,
2003.
http://www.neurology.org/cgi/eletters/60/2/176#535
SUBMITTED 3/26/03
Here is what your Post-Publication Peer Review will look like online:
Re: RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Terry S. Singeltary,
disabled
CJD WATCH,
NA
Send Post-Publication Peer Review to journal:
Re: Re: RE-Monitoring the occurrence of emerging forms of
Creutzfeldt-Jakob disease in the United States
Email Terry S. Singeltary, et al.:
flounder@wt.net
Greetings again Neurology,
i must respectfully disagree with Ryan Maddox, MPH, et al. looks like
sporadic CJDs are increasing to me, but some will just claim better
surveillance i suppose. odd how the USA can claim better surveillance
when CJD is not reportable in most states and the elderly demented do
not get autopsied in most cases. most doctors and medical personnel i
have dealt with knew absolutely nothing about CJD, much less
human/animal TSEs. so how would one know? also, i must say, this statement;
>>>In addition, because CJD is least accurately diagnosed early in the
course of illness, notifiable-disease surveillance could be less
accurate than, if not duplicative of, current mortality surveillance.<<<
this is very disturbing to me, if most elderly demented (either fast or
slow Alzheimer's and other related demented disease's are not autopsied,
and they die from disease's brought on by dementia in the terminally
ill, and this is what is put on the death certificate, then how would
mortality surveillance pick up these false diagnosis of cause of death?
several studies have shown a substantial number of misdiagnosed cases of
TSEs;
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
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)
personal communication Dr. laura manuelidis YALE;
Subject: Re: Hello Dr. Manuelidis Date: Fri, 22 Dec 2000 17:47:09 -0500
From: laura manuelidis Reply-To:
laura.manuelidis@yale.edu Organization: Yale Medical School To: "Terry
S. Singeltary Sr." References:
<39B5561A.87B84A28@wt.net> <39B64574.A4835745@yale.edu>
<39B680D8.3872535B@wt.net> <39B66EF1.4CE25685@yale.edu>
<39BBB812.425109F@wt.net> <39BE84CB.D7C0C16B@yale.edu>
<3A3BA197.7F60D376@wt.net>
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
BESIDES the increase in Switzerland, and despite the fact the U.K. did
increase from 1993 to 2002 from 37 to 63 cases of sporadic CJD, look at
France, Germany, Italy and their increase of sporadic CJDs;
http://www.eurocjd.ed.ac.uk/sporadic.htm
The number of people dying from sporadic Creutzfeldt-Jakob disease (CJD)
has risen sharply in Switzerland. The finding is raising fears that 'mad
cow disease' could have spread to humans in another form1.
http://www.nature.com/nsu/020708/020708-18.html
Nature 420, 450 (2002); doi:10.1038/420450a
Prion data suggest BSE link to sporadic CJD
DECLAN BUTLER
Predicting the number of cases of CreutzfeldtJakob disease (CJD) in
people as a result of transmission of bovine spongiform encephalopathy
(BSE) has just got more difficult.
Whereas it was thought that BSE only caused a new form of the disease
called variant CJD (vCJD), a study in mice from a team led by John
Collinge at University College London suggests that it may also cause a
disease indistinguishable from the commonest form of classical, or
'sporadic', CJD (E. A. Asante et al. EMBO J. 21, 63586366; 2002). If
the group's mouse model is relevant to the human disease, the results
also suggest that the true extent of infection may be difficult to
assess because of the large number of asymptomatic carriers.
The latest work uses mice engineered to carry the human gene for a
cell-membrane protein called PrP. Prion diseases occur when PrP is
converted to the abnormal 'prion' form, PrPSc. Collinge has developed a
test, based on a standard western blot for analysing proteins, to study
PrPSc extracted from the brain. This previously showed disease caused by
BSE or vCJD to give a characteristic molecular signature that is
distinct from sporadic CJD (J. Collinge, K. C. L. Sidle, J. Meads, J.
Ironside and A. F. Hill Nature 383, 685690; 1996).
In their latest experiments, Collinge and his team injected material
from the brains of cows with BSE or people with vCJD directly into the
brains of two strains of mice with a human PrP genotype known as 129MM.
Almost 40% of the British population has this genotype. In one mouse
strain, those that became infected showed the usual BSE pattern in the
western blot. But in the other, Collinge's team tested 11 mice infected
with BSE material using the western blot. Ten of them showed a pattern
consistent with sporadic CJD.
The number of cases of sporadic CJD have been rising in Britain since
the 1970s, and this had been attributed to better monitoring for the
condition. But in July, researchers led by Adriano Aguzzi of the
University Hospital Zurich reported a sudden increase in sporadic CJD
figures in Switzerland in 2001, and suggested that infection with BSE
might be to blame (see Nature 418, 266; 2002). Collinge's new data
provide worrying molecular evidence that BSE might be to blame for the
rise in sporadic CJD.
In previous experiments, Collinge had injected BSE and vCJD material
into mice with another human PrP genotype, known as 129VV. The new data
are thought to be more relevant to the transmission of BSE because all
of the known human victims of vCJD have the 129MM genotype. Another
worrying finding is that the 129MM mice seem to be more susceptible to
developing a subclinical infection, with no obvious symptoms.
If a large pool of the British population is carrying a subclinical BSE
infection, this would have serious consequences for the potential
transmission of the disease, for instance through contaminated surgical
instruments. And although laboratory mice are short-lived, infected
humans might go on to develop the disease later in life.
The UK Department of Health, which has been briefed by Collinge on his
findings, says that it will ask its Spongiform Encephalopathy Advisory
Committee to consider the results closely at its next meeting in
February. Collinge says that an urgent nationwide screening of tonsil
material is needed to get a better estimate of the level of infection in
the population.
Macmillan MagazinesNature © Macmillan Publishers Ltd 2002 Registered No.
785998 England.
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v420/n6915/full/420450a_r.html&filetype=&_UserReference=C0A804ED4652081347C45CB40BA13E81F597
Mouse model sheds new light on human prion disease
New findings from Professor John Collinge and his MRC Prion Unit team
have increased our understanding of human prion diseases, for example
Creutzfeldt-Jacob disease (CJD) which destroys the brain. Their work
also raises new research questions about susceptibility to exposure to
the infective agent that causes bovine spongiform encephalopathy (BSE),
a similar brain disease that affects cows. The research is published in
the 28 November 2002 edition of the European Molecular Biology
Organisation journal.
In order to study human susceptibility to BSE and the species barrier
between cattle and humans, Professor Collinges team has developed mice
which have the human form of prion protein the infectious protein, or
prion, commonly believed to cause spongiform encephalopathies. The mice
show remarkably similar damage to that seen in people, indicating that
these mice are a good model of the human disease. This means we can see
how prions from BSE and human new variant CJD (vCJD) which is believed
to be caused by BSE prion infection act on the mice to mimic human
patterns of the disease.
The experiments confirmed earlier findings that the BSE and vCJD prions
are closely similar. However, the scientists were surprised to see that
while some of the mice developed a disease pattern closely similar to
human vCJD, others produced a pattern like a form of sporadic
(classical) CJD. Sporadic CJD simply refers to a form of CJD with no
known cause (such as genetic mutation or accidental exposure to prions).
It has always been possible that it may have multiple causes. These data
suggest that some cases of apparently sporadic CJD in the UK and
elsewhere where people have been exposed to BSE prions may in fact be
caused by BSE.
Professor John Collinge said We are not saying that all or even most
cases of sporadic CJD are as a result of BSE exposure, but some more
recent cases may be the incidence of sporadic CJD has shown an upward
trend in the UK over the last decade. While most of this apparent
increase may be because doctors are now more aware of CJD and better at
diagnosing it, serious consideration should be given to a proportion of
this rise being BSE-related. Switzerland, which has had a substantial
BSE epidemic, has noted a sharp recent increase in sporadic CJD.
While few of the mice inoculated with BSE or vCJD prions showed clinical
signs of disease, which might have suggested a good species barrier,
closer examination revealed that many of the mice were in fact infected.
This finding of a sub-clinical form of prion disease has been
recognised before by this research group and now also seems relevant to
BSE infection.
Further work in the paper argues that it is the genetic makeup of the
mice which determines whether BSE infection makes them produce the type
4 prion strain (as seen in variant CJD in humans) or the type 2 strain
(as seen in sporadic CJD in humans).
©2003 Medical Research Council
http://www.mrc.ac.uk/index/public-interest/public-news/public-bse_and_sporadic_cjd.htm
i also respectfully disagree with the assumption that;
>>>Because only a very small proportion of the US population has been
exposed to CWD, a targeted surveillance and investigation of unusual
cases or case clusters of prion diseases among persons at increased risk
of exposure to CWD is a more efficient approach to detecting the
possible transmission of CWD to humans<<<
CWD is not the only TSE in the USA. we have Scrapie in sheep/goats, TME
in mink and the fact USA BSE/TSE surveillance in USA cattle to date has
been lacking, to say the least (re-recent reports from GAO). the cattle
industry has flagrantly violated the voluntary ruminant-to-ruminant
partial feed ban of 8/4/97 up and through 2002. all these TSEs being fed
to different species of animals over the decades in the USA, sub
clinical TSEs, 2nd and 3rd passage of TSEs? we must not forget that;
IN CONFIDENCE Pathology Report:
HOUND SURVEY-REFERAL OF UNRESOLVED CASES
snip...
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE
to other species will invariably present pathology typical of a
scrapie-like disease.
snip...
G A H WELLS 4 January 1991
http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
ROUND TABLE ON BSE -- WASHINGTON -- 27-28 JUNE 1989
snip...
The summary does tend to give a particular slant to the epidemiology of
BSE which is not totally sound. It is a possibility that the agent of
BSE may be in the cattle population in a number of countries already
apart from the USA and that clinical cases are occurring on rare
occasions. It is also important to off the possibility of the
relationship between BSE and certain low-temperature rendering systems.
For that reason a number of other countries apart from the USA and
France are at risk and, in particular, the Netherlands, Denmark, Germany
and Belgium. For these reasons it would be wise to move to an
international ban on the feeding of ruminant protein to ruminants.
Clearly the summary also needs to refer to the incidence of BSE in the
UK and not solely to Great Britain. No doubt this has been tidied up in
your comments on the summary conclusions. It is a pity that more of the
comments put forward by Dr. Kimberlin have not been included in the
summary since his views on page 13 are succinct and valuable...
snip...
http://www.bseinquiry.gov.uk/files/yb/1989/08/29003001.pdf
Is there a Scrapie-like disease in cattle ?
IN CONFIDENCE
R.F. MARSH
snip...
re-mink rancher 'Wisconsin' dead stock feeder using >95% downer or dead
dairy and a few horses...
http://www.bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf
As of March 11, CVM had received inspection reports covering inspections
(both initial inspections and re-inspections) of 10,458 different firms.
The majority of these inspections (around 80%) were conducted by State
officials under contract to FDA and the remainder by FDA officials.
Various segments of the feed industry had different levels of compliance
with this feed ban regulation. The results to date are reported here
both by "segment of industry" and "in total".
http://www.fda.gov/cvm/index/fdavet/2002/May_June.htm#Ruminant
2. Mad Cow Disease: Improvements in the Animal Feed Ban and Other
Regulatory Areas Would Strengthen U.S. Prevention Efforts. GAO-02-183,
January 25.
http://www.gao.gov/cgi-bin/getrpt?GAO-02-183
Food-Processing Security: Voluntary Efforts Are Under Way, but Federal
Agencies Cannot Fully Assess Their Implementation. GAO-03-342
http://www.gao.gov/cgi-bin/getrpt?GAO-03-342
i am not sure about 2003, they have ceased posting those warning
letters. it seems i now have to go through the F.O.I.A. we have been
feeding TSE infected ruminants to ruminants for decades. to only be
concerned with TSE to humans from only CWD in deer and elk in the USA,
would be foolish in my opinion. besides, it would not take too many CWD
infected humans to spread the agent via the many other vectors for
transmission (medical/surgical arena, pharmaceuticals, supplements,)
just to name a few potential routes.
with all due respect, with present data to date, further floundering on
making all CJD/TSEs reportable in the USA, and further refusal to deal
with sporadic CJDs in the USA and around the Globe without CJD
questionnaire asking questions pertaining to route and source of agent,
will only allow the agent to continue to spread, and should be regarded
with great suspicion!
thank you,
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
CJD WATCH
=============
########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
