SEARCH VEGSOURCE:

 

 

Follow Ups | Post Followup | Back to Discussion Board | VegSource
See spam or
inappropriate posts?
Please let us know.
  




From: TSS ()
Subject: THE MAD COW INVESTIGATOR ??? or mad cow plagiarism, you be the judge
Date: February 13, 2006 at 9:49 am PST



NEWS

Fundraiser; July 7th, New York, NY 6 - 8 pm
Come meet Janet, see a teaser for the work-in-progress, meet the filmmakers and hear guest-speaker Betty Fussell, historian and author of "The Story of Corn" and an upcoming book about beef. No admission will be charged but a request for donations will be made. Wine and hors d'oeuvres will be served. Email us for more information and to receive an invitation: mwm-film@earthlink.net with FUNDRAISER in the subject heading.

Host Committee: Nina Planck of Local Foods and author of the upcoming book "Real Food," Anna Lappe of the Small Food Institute, Kellogg Food & Society Fellow, Bernardo Issel of Corporate Campaign.

Project Status: We have shot many scenes following Janet's investigation and her life over the past year, and are now on fundraising push to raise money to finish the film. We aim to broadcast on PBS, ideally as part of the independent documentary series POV, or point of view, which reaches a broad audience and includes comprehensive outreach plans.

Grants still pending include: The Radziwill Documentary Fund, The Jerome Foundation, NYSCA

back to top

ABOUT THE FILM

We are producing an hour-long documentary for a national television audience that deals with beef safety issues through the personal story of an unexpected muckraker in the tradition of Erin Brokovich and Upton Sinclair.


Janet Skarbek Our story follows Janet Skarbek, a wife, mother and accountant from New Jersey in her new role as a self-proclaimed "Mad Cow Investigator". Janet is independently investigating the deaths in her area that she believes form a disease cluster and uncovering alarming information about meat production and government policy nationwide. Janet, a devout Christian, demonstrates courage and integrity as she propels herself into the midst of the media limelight to change the status quo on the issue of beef safety.

Janet's viewpoint will be balanced by perspectives of the American farmers producing beef, the scientists studying the disease, and the government officials who reassure us that our meat supply is safe. The paradox at the heart of the film is intrinsic to the mission of the USDA: how to resolve the conflict between the public health and the business interests which sustain our economy?

back to top

BACKGROUND

Janet's contention that not enough is being done to protect us from tainted beef has gained increasing credence with the unfolding of events since the first cow confirmed to be infected with BSE was discovered in Washington State in December of '03. In a recent editorial, The New York Times stated that "the Federal Department of Agriculture is making it hard for anyone to feel confident that the nation is adequately protected against mad cow disease."

The first cow infected with BSE was discovered in Washington state in December 2003. Recent developments include the cover-up (federal investigation pending) of a cow possibly infected in Texas, the secret importation of millions of pounds of banned meat product from Canada under the USDA's nose, and the refusal to allow a cattle company permission to voluntarily test all its cows for mad cow in order to re-establish the company's sales to Japan.

The calls for reform in USDA policy are getting louder, and not just from Janet. Most recently, independent Inspector General Phyllis Fong presented a critical report to Congress that recommended increasing testing for mad cow. The current testing policy is clearly teetering and we are certain that by following Janet's actions we will be able to successfully document the inevitable change in the status quo that is about to occur.

Public awareness and understanding of these events is limited due to the coverage from news outlets which breaks stories without providing context or follow-up.

The American public deserves to be better informed at this crucial time. The public's increasing interest in food issues and growing concerns about agribusiness means that our film will serve to fill a gap in comprehensive programming on the subject. Americans, like Janet Skarbek, are less and less willing to be passive about health issues affecting their lives and this project is about presenting information in a thorough and balanced manner so that awareness is increased and educated consumers can make informed decisions.

Janet is an ideal person to bring a story about food safety to a wide national audience. In an era when politicians are eager to divide us into red-staters and blue-staters, into secular city slickers versus rural Christians, Janet is both of strong faith and progressive politics. She is a normal mom with incredible courage and a role model in our time.

Part investigative report, part personal story of transformation, our film will bring new audiences to public television and inspire them to engage in this issue.

back to top

ABOUT US

Co-Directors: Nancye Good & Charlotte Buchen
Executive Producer: E. Paul DiMartino

Milky Way Media
15 Spencer Place
Brooklyn NY 11216
office: 718 360 9227
cell: 718 501 4623
email: mwm-film@earthlink.net

Milky Way Media is a full-fledged production company started by Nancye Good and her husband E. Paul DiMartino.

Nancye has been honing her sense of story development for over 10 years producing and directing programs for Japanese Network television. The projects she headed often viewed aspects of American life from the more objective viewpoint of the international media, including on-the-ground coverage of the 2000 Inauguration, a multi-segment news story on Xeno-estrogen contaminants in the food chain, and live coverage of the 1996 Democratic National Convention in Chicago. Ultimately her inspiration for pursuing this project comes from her experience covering under-reported topics, and an intense concern about the safety, quality, and flavor of the food she eats and feeds to her own children.

Charlotte's background as an independent producer and editor began at InCite Pictures/Cine Qua Non, producing documentaries for television about bank robbers ("The Trenchcoat Gang", Court TV 2003), small town Texas politics ("The Education of Shelby Knox", ITVS 2005) and other assorted projects. She co-produced and edited "Independent Media in a Time of War", a call for media awareness that is being distributed by the Media Education Foundation and has screened in over 15 festivals worldwide. She recently produced and directed "Messenger's" a short documentary about the legacy of slavery and the blues in Clarksdale Mississippi that won 1st place at the Crossroads film festival in Jackson. Charlotte hopes to bring the politics of food to the table for a wide audience with this film at a time when Americans are looking for informed critiques of agribusiness.

back to top

http://www.madcowinvestigator.com/#bg


----- Original Message -----
From: "Terry S. Singeltary Sr."
To:
Sent: Friday, February 10, 2006 10:18 AM
Subject: Re: USDA


> hi nancye,
>
>
> > I hope you are not feeling badly about it any more.
>
>
> well, considering on top of the big mac files i sent you and janet (janet
> later) and the fact i found out later even the Alzheimers documents you gave
> janet praise to i had and posted years ago. janet knew. i think i sent them
> to you too (below this long bit of data my reply to you continues)
> i probably should, but i must not loose focus, but did for a short time ;
>
>
>
>
>
>
> CJD/GSS/BSE/CWD/SCRAPIE aka MAD COW DISEASE and Alzheimer's, another
> cover-up ???
>
>
>
>
>
>
> CJD1/9 0185
>
>
> Ref: 1M51A
>
> IN STRICT CONFIDENCE
>
>
> Dr McGovern From: Dr A Wight
>
> Date: 5 January 1993
>
> Copies: Dr Metters
>
> Dr Skinner
>
> Dr Pickles
>
> Dr Morris
>
> Mr Murray
>
>
> TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
>
>
> 1. CMO will wish to be aware that a meeting was held at DH yesterday,
> 4 January, to discuss the above findings. It was chaired by Professor
> Murray (Chairman of the MRC Co-ordinating Committee on Research in
> the Spongiform Encephalopathies in Man), and attended by relevant
> experts in the fields of Neurology, Neuropathology, molecular biology,
> amyloid biochemistry, and the spongiform encephalopathies, and by
> representatives of the MRC and AFRC.
>
> 2. Briefly, the meeting agreed that:
>
> i) Dr Ridley et als findings of experimental induction of p amyloid
> in primates were valid, interesting and a significant advance in the
> understanding of neurodegeneradve disorders;
>
> ii) there were no immediate implications for the public health, and no
> further safeguards were thought to be necessary at present; and
>
> iii) additional research was desirable, both epidemiological and at the
> molecular level. Possible avenues are being followed up by DH
> and the MRC, but the details will require further discussion.
>
> 93/01.05/4.1
>
>
> http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
>
>
>
>
>
> BSE101/1 0136
>
>
> IN CONFIDENCE
>
> 5 NOV 1992
>
> CMO From: Dr J S Metters DCMO 4 November 1992
>
>
> TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
>
>
> 1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have
> recognised the public sensitivity of these findings and intend to report
> them in their
> proper context. This hopefully will avoid misunderstanding and possible
> distortion by
> the media to portray the results as having more greater significance than
> the findings
> so far justify.
>
>
> 2. Using a highly unusual route of transmission (intra-cerebral injection)
> the
> researchers have demonstrated the transmission of a pathological process
> from two
> cases one of severe Alzheimer's disease the other of Gerstmann-Straussler
> disease to
> marmosets. However they have not demonstrated the transmission of either
> clinical
> condition as the "animals were behaving normally when killed'. As the report
> emphasises the unanswered question is whether the disease condition would
> have
> revealed itself if the marmosets had lived longer. They are planning funher
> research
> to sec if the conditions, as opposed to the partial pathological process, is
> transmissible.
>
>
> What are the implications for public health?
>
>
> 3. . The route of transmission is very specific and in the natural state of
> things
> highly unusual. However it could be argued that the results reveal a
> potential risk,
> in that brain tissue from these two patients has been shown to transmit a
> pathological
> process. Should therefore brain tissue from such cases be regarded as
> potentially
> infective? Pathologists, morticians, neuro surgeons and those assisting at
> neuro
> surgical procedures and others coming into contact with "raw" human brain
> tissue
> could in theory be at risk. However, on a priori grounds given the highly
> specific
> route of transmission in these experiments that risk must be negligible if
> the usual
> precautions for handling brain tissue are observed.
>
>
> 92/11.4/1-1
>
>
> BSE101/1 0137
>
>
> 4. The other dimension to consider is the public reaction. To some extent
> the GSS
> case demonstrates little more than the transmission of BSE to a pig by
> intra-cerebral
> injection. If other prion diseases can be transmitted in this way it is
> little surprise that
> some pathological findings observed m GSS were also transmissible to a
> marmoset.
> But the transmission of features of Alzheimer's pathology is a different
> matter, given
> the much greater frequency of this disease and raises the unanswered
> question whether
> some cases are the result of a transmissible prion. The only tenable public
> line will
> be that "more research is required" before that hypothesis could be
> evaluated. The
> possibility on a transmissible prion remains open. In the meantime MRC needs
> carefully to consider the range and sequence of studies needed to follow
> through from
> the preliminary observations in these two cases. Not a particularly
> comfortable
> message, but until we know more about the causation of Alzheimer's disease
> the total
> reassurance is not practical.
>
>
>
> JS METTERS
> Room 509
> Richmond House
> Pager No: 081-884 3344
> Callsign: DOH 832
>
> 121/YdeS
>
> 92/11.4/1.2
>
>
>
>
> http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
>
>
>
>
> TSS
>
>
>
> Proof Mad Cow Is The Same
> As Alzheimer's And CJD ???
>
> How Many Of Them Are Really Mad Cow/vCJD/TSEs ???
>
> How Can Government Claims Of Just 'One In A Million' Be Accurate
> When CJD Is Not A Reportable Disease? And When The Elderly Do
> Not Get Routinely Autopsied??
>
>
> By Terry Singletary, Sr
> 12-27-03
>
>
> Note - This extensive, powerful assemblage of science was first posted on
> 1-24-3. The
> following data is even more important today. -ed
>
> snip...
>
>
> 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
> 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 examinationas 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: BSE-L@uni-karlsruhe.de
>
>
> #### 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 accountsfor 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 severityof 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
>
>
> ==============================
> 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/s1
> 94.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
>
> 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
>
> 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
>
> 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
>
> Slide show
>
> ... Many neurodegenerative disorders -- such as prion diseases, Parkinson's
> disease, Huntington's disease, Alzheimer's disease, frontotemporal
> dementia -- are ...
>
> www.nature.com/nrm/journal/v1/n3/slideshow/nrm1200_217a_F1.html
>
> Occasional PrP plaques are seen in cases of Alzheimer's Disease
>
> snip...
>
> 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
>
>
> ====================
>
> 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 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
>
> "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
>
>
>
>
> Proof Mad Cow Is The Same As Alzheimer's And CJD
> As Alzheimer's And CJD How Many Of Them Are Really Mad Cow/vCJD/TSEs ??? ...
> I have posted some data below on CJD and Alzheimer's that you may find
> interest ...
> www.rense.com/general46/proofa.html - 124k -
>
>
>
> http://www.rense.com/general46/proofa.html
>
>
>
>
>
> More Evidence Mad Cow Same As CJD And Alzheimer's
> I have posted some data below on CJD and Alzheimer's that you may find
> interest
> ... Diagnosis and Reporting of Creutzfeldt-Jakob Disease TS Singeltary, Sr;
> ...
> www.rense.com/general34/cjmd.htm - 123k -
>
>
>
>
> http://www.rense.com/general34/cjmd.htm
>
>
>
>
> TSS
>
> #################### https://lists.aegee.org/bse-l.html
> ####################
>
>
> =================
> =================
> =================
>
>
>
> Nancye, this complete ordeal with you and janet really set me back and
> almost made me stop.
> knowing janet was still lurking on voice, i took my marbles home for a
> while and stopped posting to cjd voice because of it, and just about stopped
> all together. but found that this was not the answer and have put it behind
> me, the 'cause' is more important, and i must not loose focus over getting
> my feelings hurt. gotta moove on. SOooo;
>
>
>
>
>
> NOW, you ask;
>
>
> > If you are interested, please let me know.
>
>
> yes, go ahead and send the final version, ill read it. did not even know if
> it went out and if it had changed since the cut you sent me. dont know if i
> can read it again, but will try and do it from a different point of view
> this time.
>
>
>
> > I have been contacted by Newsweek Japan a few times since then and I
> > gave them your contact information both times. Have they contacted you?
>
>
>
> yes ;
>
>
> >>>>>Terry,
>
> Thank you for all of the information, I really appreciate it. I will plan on
> giving you a call tomorrow to talk further about your experiences. If there
> is a particular time that suits you please let me know, otherwise I will
> plan on around 2 EST. Thanks again!
>
> Traci Carpenter<<<<<<<<<
>
>
> SHE called, we spoke, that was that, have not heard back or if any article
> was written.
> nobody much tells me nothing after the facts ;-) this is normal procedure.
>
>
> > The last time they contacted me they were inquiring about a recent
> > USDA report that mentioned a couple of violations where downer cows
> > were slaughtered and processed. Newsweek Japan is considering doing
> > a story on this. Do you know anything about this report? If they
> > ask me to write something about it I would like to feature your story
> > in the article.
> >
> > Please take care, and give my regards to Bobbie.
>
>
>
> nancye, so soon you forget since being at my home, thats Bonnie, not bobbie
> :-)
>
>
> about that report, just happen to have it right here, will forward long
> version to you later, getting ready to climb back on the saddle at
> voice.................
>
> if the story runs, you know how to spell it now i hope, dont you :-)
>
>
> HEIDENHAIN VARIANT CREUTZFELDT JAKOB DISEASE
> 'confirmed' DOD 12-14-97 Barbara Singeltary Poulter
>
>
>
> here is report you wanted, will send you johanns lies and my comments later;
>
>
>
> Audit Report Animal and Plant Health Inspection Service Bovine Spongiform
> Encephalopathy (BSE) Surveillance Program - Phase II and Food Safety and
> Inspection Service Controls Over BSE Sampling, Specified Risk Materials, and
> Advanced Meat Recovery Products - Phase III
>
>
>
> UNITED STATES DEPARTMENT OF AGRICULTURE OFFICE OF INSPECTOR GENERAL
> Washington, D.C. 20250 January 25, 2006 REPLY TO ATTN OF: 50601-10-KC TO: W.
> Ron DeHaven Administrator Animal and Plant Health Inspection Service Barbara
> Masters Administrator Food Safety and Inspection Service ATTN: William J.
> Hudnall Deputy Administrator Marketing Regulatory Program Business Services
> William C. Smith Assistant Administrator Office of Program Evaluation,
> Enforcement, and Review FROM: Robert W. Young /s/ Assistant Inspector
> General for Audit SUBJECT: Animal and Plant Health Inspection Service -
> Bovine Spongiform Encephalopathy (BSE) Surveillance Program - Phase II and
> Food Safety and Inspection Service - Controls Over BSE Sampling, Specified
> Risk Materials, and Advanced Meat Recovery Products - Phase III This report
> presents the results of our audit of the enhanced BSE surveillance program
> and controls over specified risk materials and advanced meat recovery
> products. Your written response to the official draft report, dated January
> 20, 2006, is included as exhibit G with excerpts of the response and the
> Office of Inspector General's (OIG) position incorporated into the Findings
> and Recommendations section of the report, where applicable. We accept the
> management decisions for all recommendations. Please follow your agency's
> internal procedures in forwarding documentation for final action to the
> Office of the Chief Financial Officer (OCFO). We are providing a separate
> memorandum to the agencies and OCFO that provides specific information on
> the actions to be completed to achieve final action. We appreciate your
> timely response and the cooperation and assistance provided to our staff
> during the audit USDA/OIG-A/50601-10-KC/ Page i
>
> Executive Summary
>
> Animal and Plant Health Inspection Service - Bovine Spongiform
> Encephalopathy (BSE) Surveillance Program - Phase II and Food Safety and
> Inspection Service - Controls Over BSE Sampling, Specified Risk Materials,
> and Advanced Meat Recovery Products - Phase III
>
> Results in Brief This report evaluates elements of the interlocking
> safeguards in place to protect United States (U.S.) beef from Bovine
> Spongiform Encephalopathy, widely known as BSE or "mad cow disease." Since
> 1990, the U.S. Department of Agriculture (USDA), Animal and Plant Health
> Inspection Service (APHIS), has led a multi-agency effort to monitor and
> prevent BSE from entering the food supply. After discovering a BSE-positive
> cow in December 2003, APHIS expanded its BSE surveillance program. To
> further protect the food supply, USDA banned materials identified as being
> at risk of carrying BSE (specified risk materials (SRM)), such as central
> nervous system tissue. As part of this effort, USDA's Food Safety and
> Inspection Service (FSIS) required beef slaughter and processing facilities
> to incorporate controls for handling such materials into their operational
> plans. Onsite FSIS inspectors also inspect cattle for clinical signs in
> order to prevent diseased animals from being slaughtered for human
> consumption. To evaluate the effectiveness of the safeguards, we assessed
> APHIS' implementation of the expanded surveillance program, as well as FSIS'
> controls to prevent banned SRMs from entering the food supply.
>
> In June 2004, APHIS implemented its expanded surveillance program;
> participation by industry in this surveillance program is voluntary. As of
> May 2005, over 350,000 animals were sampled and tested for BSE. To date, two
> animals tested positive for BSE; one tested positive after implementation of
> the expanded surveillance program.
>
> USDA made significant efforts to implement the expanded BSE surveillance
> program. Much needed to be done in a short period of time to establish the
> necessary processes, controls, infrastructure, and networks to assist in
> this effort. In addition, extensive outreach and coordination was undertaken
> with other Federal, State, and local entities, private industry, and
> laboratory and veterinary networks. This report provides an assessment as to
> the progress USDA made in expanding its surveillance effort and the
> effectiveness of its controls and processes. This report also discusses the
> limitations of its program and data in assessing the prevalence of BSE in
> the U.S. herd.
>
>
>
> snip...
>
>
>
>
> 40 ELISA test procedures require two additional (duplicate) tests if the
> initial test is reactive, before final interpretation. If either of the
> duplicate tests is reactive, the test is deemed inconclusive.
>
> 41 Protocol for BSE Contract Laboratories to Receive and Test Bovine Brain
> Samples and Report Results for BSE Surveillance Standard Operating Procedure
> (SOP), dated October 26, 2004.
>
> 42 The NVSL conducted an ELISA test on the original material tested at the
> contract laboratory and on two new cuts from the sample tissue.
>
> 43 A visual examination of brain tissue by a microscope.
>
> 44 A localized pathological change in a bodily organ or tissue.
>
> SNIP...
>
>
> PLEASE SEE FLAMING EVIDENCE THAT THE USDA ET AL COVERED UP MAD COW DISEASE
> IN TEXAS ;
>
>
> PAGE 43;
>
>
> Section 2. Testing Protocols and Quality Assurance Controls
>
>
> snip...
>
>
> FULL TEXT 130 PAGES
>
>
>
> http://www.usda.gov/oig/webdocs/50601-10-KC.pdf
>
>
> TSS
>
>
>
>
>
> kind regards,
> terry
>
>
>
>
>
> ----- Original Message -----
> From:
> To: "Singeltary Sr."
> Sent: Friday, February 10, 2006 8:58 AM
> Subject: USDA
>
>
> > Dear Terry,
> >
> > I hope you are doing well. The article for Newsweek Japan came out,
> > I would forward it but it's all in Japanese. If you are interested,
> > please let me know. I have no idea if it made big ripples or not,
> > but the magazine seemed happy with my story.
> > I hope you are not feeling badly about it any more.
> >
> > I have been contacted by Newsweek Japan a few times since then and I
> > gave them your contact information both times. Have they contacted you?
> >
> > The last time they contacted me they were inquiring about a recent
> > USDA report that mentioned a couple of violations where downer cows
> > were slaughtered and processed. Newsweek Japan is considering doing
> > a story on this. Do you know anything about this report? If they
> > ask me to write something about it I would like to feature your story
> > in the article.
> >
> > Please take care, and give my regards to Bobbie.
> >
> > Nancye Good
> > (347) 661-4204
> >
>

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

----- Original Message -----
From: "Nancye Good"
To: "Terry S. Singeltary Sr."
Sent: Monday, January 23, 2006 12:05 PM
Subject: You deserve better. Much better.


> Terry,
>
> I feel badly about not including you in the article. But I never got
> the feeling when we met you at your home that you were doing this to get
> exposure for yourself. I didn't get the letters from Janet, either, you
> sent them to me.
>
> If I had sensed from you that you required a credit I certainly would
> have mentioned you. I should have anyway. I was trying to write a
> strong article that would get published. I wasn't thinking about who
> deserved what. I was just trying to make a good story that people would
> be interested in reading. My bad. Although I think of you and Janet
> and Lester Friedlander and Howard Lyman as a team, working for a common
> cause, I should have known there is a certain amount of rivalry, just as
> there seems to be among the scientists.
>
> Previously I had sent a list of topics I had covered with the Japanese
> TV crew to the Newsweek Japan editor and when the ban was reinstated, he
> finally had a window of opportunity where they could write a story and
> asked to hear follow up. By the way, NHK is still saying no to the
> producers about the tv show we interviewed you for, because of pressure
> from US beef producers.
>
> I should have thought about the repercussions and given credit all round
> but I had one day to write an article. I was under a lot of pressure.
> If I had any inkling about how much it meant to you, I certainly would
> have included your efforts somehow. I thought you would be happy that
> the message is hopefully getting out. From what I can tell, Newsweek
> Japan does not have the readership that some other Japanese weekly
> magazines have that probably have featured articles about you. It may
> not make much of a difference at all.
>
> Hopefully, this article will help the producers I visited you with get
> their show produced!
>
> For what it's worth, Terry, I owe you one, big time. Please don't stop
> your efforts because of my stupid mistake.
>
> Nancye Good
>
>
>
> Terry S. Singeltary Sr. wrote:
>
> > well janet, i just read the article coming out in japan by mwm nancy
> > et al.
> > i have to say, you got me again. and i just keep falling for the same
> > old song-and-dance.
> > first it was the NYT article and now this one ;-)
> > i fugured as much with your phone call this weekend. but like a dumb
> > ass, i send the data.
> > i keep telling myself, just let it ride, you must give them the data,
> > it's far the cause, but actually,
> > i am beginning to feel like an old prostitute. the time is coming for
> > me to tell my story, all of it, and i will
> > tell all of it...ALL of it. you can take that to the bank .............TSS
> >
> >
> >
> > >>>I feel like such a jerk that I didn't include your story except for
> > saying "other citizens."
> >
> > and you very well should..........
> >
> > Please forgive me! SNIP... It may be too late, but it is important to
> > acknowledge the person who provided access to the scientists and
> > McDonalds' letters; another activist named Terry Singeltary whose
> > mother died of the Heidenhain Variant of CJD in 1998. ........<<<
> >
> > unbelievable. i cannot believe this........but figured as much when
> > janet called yesterday and i sent her those studies. i don't suppose i
> > will ever learn, but i keep saying to myself, you must still give them
> > the data... it's getting harder and harder... THIS may be the tip of
> > the iceburg where i get off...
> >
> >
> > saddened and disgusted again in Bacliff, Texas..................tss
> >
> >
> >
> >
> > ----- Original Message -----
> > *From:* mwm-film@earthlink.net
> > *To:* Terry S. Singeltary Sr.
> > *Sent:* Monday, January 23, 2006 10:36 AM
> > *Subject:* Re: Nancye Good writes Mad Cow Disease article for
> > Newsweek Japan
> >
> > Dear Terry,
> > I hope you are doing well. I feel like such a jerk that I didn't
> > include your story except for saying "other citizens." Please
> > forgive me! I tried to make it up to you by the email below and I
> > will let you know what his reply is. I hope the article makes it
> > to print. Since it will be translated into Japanese, I'm not sure
> > what the end result will be. Janet has received a lot of media
> > coverage in Japan and that was what they asked me to write about -
> > a follow up story. I was surprised that the McDonalds letter
> > hasn't received any coverage over there at all! In Takeda san's
> > last email he indicated that they may want more stories so I may
> > have a chance to redeem myself. If so I will talk about your
> > mother's situation for sure.
> > I hope you are doing very well.
> > Take care,
> > Nancye Good
> >
> > Dear Takeda sama,
> > It may be too late, but it is important to acknowledge the person
> > who provided access to the scientists and McDonalds' letters;
> > another activist named Terry Singeltary whose mother died of the
> > Heidenhain Variant of CJD in 1998. He has been toiling for eight
> > long years gathering documents about CJD and BSE. Maybe there is
> > an online version of the article that could give him credit
> > somehow because his efforts have really been extraordinary.
> > Thank you,
> > Nancye Good
> >
> > On Jan 23, 2006, at 11:09 AM, Terry S. Singeltary Sr. wrote:
> >
> >> i hope you mentioned my mothers death of the Heidenhain Variant
> >> of CJD 'confirmed' and my efforts over the past 8 years...it
> >> would mean alot..........thanks///
> >>
> >>
> >> kind regards,
> >> terry
> >>
> >>
> >>
> >>
> >> ----- Original Message -----
> >> *From:* mwm-film@earthlink.net
> >> *To:* mwm-film@earthlink.net
> >> *Sent:* Monday, January 23, 2006 9:48 AM
> >> *Subject:* Nancye Good writes Mad Cow Disease article for
> >> Newsweek Japan
> >>
> >> Dear Friends and Colleagues,
> >>
> >> This past? Friday, Japan reinstated the ban on American beef
> >> imports due to some spinal remnants that were discovered in a
> >> shipment.? Late Friday night I received a request from the
> >> editor of Newsweek Japan to write an article about our
> >> coverage of mad cow disease for our documentary "The Mad Cow
> >> Investigator."? He wanted an article within a 24 hour
> >> turnaround.? So I wrote one.? Since I have been following the
> >> topic for almost two years I had more than enough material to
> >> write a 1500 word article.? I did some hunting Saturday
> >> morning and realized that no one had done much coverage on a
> >> letter that McDonalds' (the fast food chain, the big one)
> >> vice president had written on the 19th of December '05
> >> strongly criticizing the USDA for not taking strong enough
> >> precautions against mad cow disease, even though this letter
> >> had gone out on the AP wire.? The letter was a response to
> >> another letter written by seven prominent scientists studying
> >> BSE (mad cow disease) and the potential risk to humans that
> >> is dated 12/20.??
> >>
> >> I focused my article on these letters and what they mean for
> >> our protagonist, Janet Skarbek and other citizens who have
> >> been fighting hard to get the word out about mad cow
> >> disease.? The editor in Japan was very happy, saying "I am
> >> sure the piece is strong and quite impressive for
> >> our?readers. I really appreciate your help."? The Newsweek
> >> article should come out this Wednesday, unless the beef
> >> industry puts on the pressure, which seems unlikely since
> >> McDonalds has brought out the big guns and is now putting
> >> pressure on the USDA.? McDonalds was not alone, either.?
> >> Pfiser, and Land of Lakes also wrote letters to the FDA
> >> demanding stronger regulation and condemning the partial food
> >> bans that do little to protect Americans from Mad Cow Disease.
> >>
> >> It seems unprecedented for a major corporation to self
> >> regulate in this manner.? At the same time, it makes sense
> >> because McDonalds would be the one facing the lawsuits if
> >> anyone is proven to have died of CJD from eating big macs
> >> (seems unlikely but maybe there's new data that hasn't been
> >> released?)
> >>
> >> The rough cut of our documentary is almost finished.? These
> >> letters from the scientists and major US corporations
> >> certainly constitute a major breakthrough for our protagonist
> >> and will make for a satisfying climax in our story.? I am
> >> attaching the letters here.? If anyone is interested in
> >> reading my article, let me know.
> >>
> >> Thanks, and I will keep you updated on the progress of our
> >> documentary.
> >>
> >> Sincerely yours,
> >> Nancye Good
> >>
> >> ------------------------------------------------------------------------
> >>
> >>
> >> ------------------------------------------------------------------------
> >>

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

----- Original Message -----
From: "Nancye Good"
To: "Terry S. Singeltary Sr." ; "Janet Skarbek"
Sent: Monday, January 23, 2006 6:19 PM
Subject: bad day


> Hi Terry,
>
> It is not fair for you to think Janet is to blame for the content of my
> article. I have been doing a documentary about her since May of 2004
> and I am sure I mentioned that to you when I initially contacted you
> about the Japanese TV shoot. I have worked for Japanese TV for years
> and from that work I became aware of the messed up things in food that
> the Japanese public hears about but Americans never hear. In 1998 I
> worked on a big news program about dioxin and that made me want to do a
> similar story about food for the American audience. I read about Janet
> from a tiny news piece that came out in Dec 03 and contacted her and she
> agreed to open her life up to us. She is a good protagonist from a
> journalistic point of view because she comes from a conservative
> background and has gone through a personal change because of mad cow.
> You would also be a great protagonist because of the drama with your
> mother and the stress because of your son, and your neighbor, and the
> supplements and everything, but for me, it's too far to go to Texas.
>
> I am funding this documentary from my pocket on the super cheap on a
> mini DV with amateur camera people most of the time. We have been
> applying for grants but nothing has been forthcoming. The Japanese
> producer said I could use the footage we shot with you (and with
> scientists and Lester Friedlander etc.) but since the network declined
> their program, I am not sure if they will come through on their word at
> this point. I have been negotiating with them and this Newsweek article
> should help. I don't have a broadcast deal and at this rate for my
> documentary, I may be on the road just like Howard Lyman to try to get
> people to watch it, which is totally amazing and to be respected. I do
> know people in TV in Japan, though so maybe that helps, but I really
> want it to be seen in the US. That is my goal. I am trying!
>
> Janet is really a good, noble person. She is not trying to get the
> spotlight and I do not recall discussing the New York Times article with
> you, or at least I do not recall feeling the bitterness you are
> expressing now.
>
> Terry, you deserve a medal for the research you have done. So does
> Janet, so does everyone. Your work is very important and appreciated
> Terry.
> Thank you for not sending the article out. I'll let you know what the
> final article really says. I'm not even sure what it will include b/c
> they probably took great liberties with the translation.
>
> The scientists banded together on their 12/20 letter. In my humble
> opinion, I think that's the most effective way to make changes.
> United. If there is another opportunity, I will make more effort to
> give credit where due in the future.
>
> Sincerely yours,
> Nancye Good
>
> Terry S. Singeltary Sr. wrote:
>
> > janet et al,
> >
> >
> > > I'm not sure where all this is coming from. I always think of us as
> > a team
> >
> >
> > your kidding right?
> >
> >
> > first you come to me as a friend of a someone whom died from CJD years
> > ago, then i find out you are an author, and someone tied into the
> > media, that gets to write there own articles, that had quit her job
> > trying to cash in on a book deal and documentary on CJD. fine, someday
> > i may do one, but i will tell everyone up front, whom i am from the
> > beginning. also, it will not be about me trying to be the next Erin
> > Brockovich if i get to write the articles myself;
> >
> >
> >
> >
> > =================================
> > -------- Original Message --------
> > Subject: Re: back from vacation
> > Date: Wed, 2 Jul 2003 14:20:28 -0400
> > From: "Janet Skarbek"
> > To: "Terry S. Singeltary Sr."
> > CC:
> > References: <003101c340a3$e7a78bf0$5a8f2e44@OfficeComputer>
> > 3F030059.5060105@wt.net
> >
> >
> >
> >
> >
> >Hi Terry,
> >
> >I'm not normally a reporter. I'm a CPA and a tax specialist by training. I
> >have a book out called "Planning Your Future: A Guide for Professional
> >Women" -- and I'm a mom. But when this came up and I put the Garden State
> >people together because my mother worked there -- I decided if no one else
> >was going to write the article, I mine as well do it myself. The Burlington
> >County Times changed the article a lot. I have many problems with the final
> >form -- but I guess at least it's out there now.
> >
> >Also being in the media now gives me the lower rates (no search charges)
> >under the Freedom of Information Act at the CDC. ...snip
> >
> >
> >
> >=======================================
> >
> >
> >
> > *(CBS) *New Jersey's *Janet **Skarbek* may very well be the next *Erin
> > **Brockovich*.
> >
> >
> >
> > CBS News | Mad Cow Disease In New Jersey? | April 28, 2004 11:56:30
> >
> > (CBS) New Jersey's *Janet Skarbek* may very well be the next *Erin
> > Brockovich*. *...*
> > *Skarbek* believes the common thread that ties the *CJD* deaths
> > together is meat *...*
> > www.cbsnews.com/stories/2004/04/28/
> > earlyshow/contributors/melindamurphy/main614154.shtml - 68k -
> >
> >
> >
> > CBS News | Mad Cow Disease In New Jersey? | April 28, 2004 11:56 *...*
> >
> > *...* *Janet* *Skarbek* may very well be the next *Erin* *Brockovich*.
> > *...* says, "The number of cases
> > that *Janet* *Skarbek* has brought *...* cow disease, but from
> > sporadic *CJD*, the type *...*
> > cbsnews.cbs.com/stories/2004/04/28/
> > earlyshow/contributors/melindamurphy/main614154.shtml - 57k -
> > Supplemental Result -
> >
> >
> >
> > The amateur sleuth, the *CJD* victims, and the link to a day at the
> > *...*
> > *...* *Janet* *Skarbek*, 36, is getting attention for her theory
> > because it *...* for a Carol Olive,
> > who had also died of *CJD*. *...* when I almost fell over," Ms
> > *Skarbek* told the NYT *...*
> > millennium-debate.org/ind7ap044.htm - 16k - Supplemental Result -
> >

SNIP...

----- Original Message -----
From: "Terry S. Singeltary Sr."
To: "Terry S. Singeltary Sr." ;
Sent: Monday, February 13, 2006 11:58 AM
Subject: Re: USDA


> o.k., game over, i tried.........tss
>
>
> ----- Original Message -----
> From: "Terry S. Singeltary Sr."
> To: "Terry S. Singeltary Sr." ;
>
> Sent: Sunday, February 12, 2006 12:31 PM
> Subject: Re: USDA
>
>
> > nancye,
> >
> > do you want me to run with your original story or not???
> > did you get the files you ask for???
> >
> > kind regards,
> > terry
> >
> >
> >
> > ----- Original Message -----
> > From: "Terry S. Singeltary Sr."
> > To:
> > Sent: Friday, February 10, 2006 10:18 AM
> > Subject: Re: USDA
> >
> >
> > > hi nancye,
> > >
> > >
> > > > I hope you are not feeling badly about it any more.
> > >
> > >
> > > well, considering on top of the big mac files i sent you and janet
> (janet
> > > later) and the fact i found out later even the Alzheimers documents you
> > gave
> > > janet praise to i had and posted years ago. janet knew. i think i sent
> > them
> > > to you too (below this long bit of data my reply to you continues)
> > > i probably should, but i must not loose focus, but did for a short time
> ;
> > >
> > >
> > >
> > >
> > >

SNIP......END......loosing focus again, VERY DISGUSTED.........TSS




Follow Ups:



Post a Followup

Name:
E-mail: (optional)
Subject:

Comments:

Optional Link URL:
Link Title:
Optional Image URL: