Consumption of beef tongue: Human BSE risk associated with exposure to lymphoid tissue in bovine tongue in consideration of new research findings - Scientific Opinion of the Panel on Biological Hazards
Question number: EFSA-Q-2007-110
Adopted date: 17/04/2008
Summary
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej700_bovine_tongue_summary_en.pdf
Opinion
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej700_bovine_tongue_en.pdf
Summary
Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the human BSE risk associated with exposure to lymphoid tissue in bovine tongue in consideration of the findings included in a scientific article recently published on the consumption of beef tongue and the risk for public health.
This scientific article describes the distribution of lymphoid tissue in bovine tongue and the location of bovine lingual tonsil. In addition, it concludes that the method currently prescribed for harvesting bovine tongues in slaughterhouses is not appropriate for removing all specified risk material (SRM) and proposes an alternative harvesting method.
EFSA was requested (i) to evaluate the design of the study and its scientific validity in relation to the distribution of lymphoid tissue in bovine tongue and (ii) to evaluate the conclusions and recommendations of the study in relation to BSE risk from bovine tonsil following the harvesting method currently prescribed by EU legislation compared to the alternative one proposed in the study.
The BIOHAZ Panel reviewed the scientific article and concluded that the study further confirms and extends observations that the lingual tonsil at the base of the tongue may not be entirely eliminated when harvesting tongues by means of the method currently prescribed.
In reply to the second request, the BIOHAZ Panel assessed different parameters in order to quantify the human exposure risk to BSE from bovine tonsil associated with the consumption of bovine tongue. It was concluded that, overall, the level of infectivity in bovine tonsil is low. This, together with the declining and overall low BSE prevalence and the current policy on SRM removal, suggests a very low, if not negligible, human BSE exposure risk associated with exposure to lymphoid tissue in bovine tongue harvested as currently prescribed by EU legislation. The BIOHAZ Panel further concluded that currently there are not sufficient quantitative data available allowing a comparison of the human BSE exposure risk reduction achieved by the alternative tongue harvesting method proposed by the study in comparison to the harvesting method currently prescribed. However, it is likely that the proposed method would only provide a marginal reduction in the risk from bovine tonsil compared to the one currently prescribed.
Following to this, the BIOHAZ Panel made a series of recommendations on the topics that might be addressed in future studies on the subject.
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178704312961.htm
Annex 1
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/annex_1_bovine_tongue_translation.pdf
3.1.2. Experimental BSE cases after oral challenge. • In a sequential kill pathogenesis study of BSE in which calves were experimentally infected by oral exposure to 100g of a pool of BSE affected brainstems (a dose considered far in excess of most natural exposures (Arnold et al., 2007)), palatine tonsil was assayed in conventional mouse strains from all time points (2-40 months post-exposure). No infectivity was detected (Wells et al., 1998; Wells et al., 2005). • Palatine tonsil from this sequential kill pathogenesis study was further assayed by intracerebral inoculation of cattle, which provides a 500 fold (log10 2.7) greater sensitivity of detection of the BSE agent than the RIII mouse assay (Wells et al., 2005). A pooled inoculum was prepared from palatine tonsil of cattle (3, 3, 3 and 1 respectively) at each of 6, 10, 18, and 26 month periods post-exposure (corresponding to 10, 14, 22 and 30 months of age) from the oral challenge study. One ml of a ten per cent tissue homogenate in saline was injected by the intracerebral route into groups of 5 calves. Results indicated traces of infectivity in the palatine tonsil of cattle killed ten months after experimental oral exposure, with transmission occurring in 1 of the 5 challenged calves (Wells et al., 2005). An infection rate of 1 out of 5 suggests that the infectivity is close to the limit of detection of the assay and that the titre of infectivity in tonsil is less than 1 cattle i.c. ID50/g. The study was completed in 2006, without further transmission to any of the 4 remaining calves (Veterinary Laboratory Agency, unpublished data). • Palatine tonsil collected from a further sequential-kill pathogenesis study of BSE in which 100 calves were exposed to 100g of a pool of BSE affected brainstems (Arnold et al 2007) was also bioassayed. In this study, Espinosa et al. (2007) inoculated tonsil tissue intracerebrally into mice expressing bovine PrP (BoPrP-Tg110). The inocula originated from pooled samples from three cattle at each of five time points (20, 24, 27, 30 and 33 months) after the oral exposure of calves. Infectivity was detected at all of the time points tested, with infection rates in the mice of 1/6, 1/6, 1/5, 1/6 and 1/6 respectively. Interestingly, this would seem to indicate a relatively low constant plateau level of infectivity in the tonsil throughout this largely preclinical period. The low infection rate (1 out of 6) is consistent with a level of infectivity lower than 1 i.c.ID50 in Tgbov mice. Buschmann and Groschup (2005) provide data on a Tgbov mice model giving a 1.000-10.000 fold greater sensitivity than the cattle bioassay. While the Tgbov mice (tg110) in the study of Espinosa et al. (2007) were different from the TgbovXV mice used by Buschmann and Groschup (2005), their sensitivity is likely to be similar based on comparable levels of over expression of the bovine PrP gene in each model. From data provided by titrations of BSE infectivity in brain by the i.c. and the oral routes in cattle it has been calculated that one bovine oral ID50 = 105.5 bovine i.c. ID50 (Wells et al., 2007). On this basis, the titre of infectivity in tonsil is less than 10-5.5 bovine oral ID50/g; an estimate, using additional data, that is closely similar to that provided previously (EFSA 2004). Given the greater sensitivity of the Tgbov mouse assays than the cattle i.c. assay, it would seem probable that even in cattle after exposure to a 100g oral dose, the titre in terms of bovine oral ID50/g may be at least one order of magnitude less (i.e. 10-6.5 bovine oral ID50/g), for at least part of the incubation period. As the majority of exposures in the epidemic were probably less than 1g (Arnold et al., 2007), the infectivity in tonsil might well have occurred at an even lower titre and have peaked later in incubation. The most optimistic estimate might be that with doses of the order of less than 1g, tonsil never contains detectable levels at any time in the disease course. A table summarising the key parameters of the infectivity studies mentioned in section 3.1 can be found in Appendix A. In summary, the available data on BSE infectivity in tonsil indicate that: • The frequency with which detectable infectivity occurs in tonsillar tissue of a BSE naturally infected animal is difficult to estimate. Although only two cases have been investigated employing biological assay, infectivity has not been detected in palatine tonsil from naturally occurring clinical cases. • From sequential kill pathogenesis studies in experimentally infected cattle, infectivity associated with tonsil could be detected at 10 months post-exposure and, in the preclinical period, 20-33 months post-exposure (Wells et al., 2005; Espinosa et al., 2007), suggesting that, in this model, infectivity in tonsil probably persists throughout the disease course. • In the experimental exposure to a 100g dose, infectivity titer can be estimated from the data available to be 10-6.5 bovine oral ID50 per gram of tonsilar lymphoid tissue. • It must also be noted that all available data on infectivity relate to palatine tonsil. Occurrence and comparable levels of infectivity in lingual tonsil is an assumption. 3.2. Amount of lymphoid tissue associated with the tongue intended for human consumption As mentioned above, the findings of the study from Casteleyn et al. (2007) are consistent with those of other studies carried out in Great Britain (Wells et al., 2005) and Germany (Rebmann et al., submitted for publication), but provide no quantification of lymphoid tissue remaining in tongues intended for human consumption. Examination of 251 tongues, derived from 15 abattoirs in Great Britain after removal of SRM and intended for human consumption, showed that visible identifiable lingual tonsillar tissue, indicated by fossulae, remained in 76.5% of them (192 out of 251) (Wells et al., 2005). Even in the tongues in which no visible tonsillar tissue remained, histological examination revealed lymphoid tissue in more than 90% of them. Variations in the distribution of the lingual tonsil suggested that even after the most rigorous trimming of the tongue traces of tonsillar tissue may remain. However, the histological examination did not extend rostral to the most caudal of the filiform papillae, which occur caudal to the most caudal vallate papillae. In Germany (Rebmann et al., submitted for publication), specimens of the lingual mucosa were taken from thirty cattle immediately after slaughter. The main parameter to identify the lymphoreticular tissue in this study was the immunohistochemical identification of the follicular dendritic cells (FDC). Lymph follicles were detected in areas up to 30 mm rostral to a given macroscopic landmark (i.e. the most caudal of the vallate papilla). This is an area which would not be removed from the tongue when implementing the measures foreseen by Regulation (EC) No 999/2001. Alternative technical approaches for the removal of the lingual tonsil’s tissue, similar to those by Casteleyn et al. in 2007, are proposed by the authors. These scientific studies did not take into account the rostral part of the tongue which can harbor solitary primary lymph nodules or diffuse accumulations of T and B lymphocytes. Some information on more rostral areas of the tongue was provided in a more recent study (Kato and Sawada, 2008). In that study, examination of the bovine tongue was carried out from the tip of the torus linguae to the root of the tongue. The study confirmed previous results in relation to the distribution of lymphoid tissue in bovine tongue. In addition, 1 out of the 20 specimens collected rostrally to the most rostral vallate papilla contained lingual tonsillar tissue. Based on the above data, neither qualitative nor quantitative estimation of the significance of the lymphoid formations located rostrally to the most caudal vallate papilla is feasible at present. In the DNV risk assessment cited in section 3.1 (EFSA, 2004; SEAC, 2003), a total weight of bovine tonsil of 50g is assumed. However, in the DNV risk assessment, it is stated that the weights of the various tissues were taken from the LFRA ruminant products audit (LFRA, 1997). The total weight of tonsillar tissue in a typical bovine, as given from literature derived offal weights in the LFRA audit, is estimated at 200g. This suggests that the value of 50g in the DNV report is in fact referring to the weight of lingual tonsil. If the largest contribution to the total weight of tonsillar material is the palatine tonsil, it would be reasonable to estimate lingual tonsil as approximately 50g. It is further assumed in the DNV risk assessment that, after removal of all visible tonsillar tissue, the realistic upper limit of tissue that would remain in the tongue would be 10% i.e. 5g. Since the palatine tonsil is a circumscribed structure and easily identified, complete removal, compared to the lingual tonsil, is ensured, so this estimate remains valid as the quantity of tonsillar tissue that might not be removed. In conclusion, based on the data available:
• it is not possible to know exactly the quantity of lymphoid tissue remaining in bovine tongue intended for human consumption when harvested according to the harvesting method currently applied, even if it can be estimated to be 5g;
• it is not possible to estimate how much lymphoid tissue is removed by the alternative harvesting method compared with the one currently applied.
snip...full text ;
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej700_bovine_tongue_en.pdf
SRM MAD COW RECALL 406 THOUSAND POUNDS CATTLE HEADS WITH TONSILS KANSAS
http://cjdmadcowbaseoct2007.blogspot.com/2008/04/srm-mad-cow-recall-406-thousand-pounds.html
Subject: [madcow] Substances Prohibited From Use in Animal Food or Feed [Docket No. 2002N-0273] (Formerly Docket No. 02N-0273) RIN 0910-AF46 Friday, April 25, 2008
http://madcowfeed.blogspot.com/2008/04/substances-prohibited-from-use-in.html
SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE
http://downercattle.blogspot.com/
MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html
Tuesday, April 29, 2008
Interference at the EPA - Science and Politics at the U.S. Environmental Protection Agency
please see full text ;
http://sciencebushwhacked.blogspot.com/
TSS
Wednesday, April 30, 2008
Thursday, April 17, 2008
Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47
[Federal Register: April 17, 2008 (Volume 73, Number 75)] [Rules and Regulations] [Page 20785-20794] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr17ap08-7]
======================================================================= -----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 189 and 700
[Docket No. 2004N-0081] RIN 0910-AF47
Use of Materials Derived From Cattle in Human Food and Cosmetics
AGENCY: Food and Drug Administration, HHS.
ACTION: Interim final rule and request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is amending its regulations on the use of materials derived from cattle in human food and cosmetics. In these regulations, FDA has designated certain materials from cattle as ``prohibited cattle materials'' and has banned the use of such materials in human food, including dietary supplements, and in cosmetics. Prohibited cattle materials include specified risk materials (SRMs), the small intestine of all cattle unless the distal ileum is removed, material from nonambulatory disabled cattle, material from cattle not inspected and passed for human consumption, or mechanically separated (MS) (Beef). Specified risk materials include the brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia of cattle 30 months of age and older, and the tonsils and distal ileum of the small intestine of all cattle. FDA is amending its regulations so that FDA may designate a country as not subject to certain bovine spongiform encephalopathy (BSE)-related restrictions applicable to FDA regulated human food and cosmetics. A country seeking to be so designated must send a written request to the Director of FDA's Center for Food Safety and Applied Nutrition, including information about the country's BSE case history, risk factors, measures to prevent the introduction and transmission of BSE, and any other relevant information.
DATES: This interim final rule is effective July 16, 2008. Submit written or electronic comments on this interim final rule by July 16, 2008. Submit comments on information collection issues under the Paperwork Reduction Act of 1995 by May 19, 2008 (see the ``Paperwork Reduction Act of 1995'' section of this document).
snip...
Table 1.--Top 10 Countries Exporting Specified North American Industry Classification System (NAICS) Code Products to United States for 2006 NAICS 311611\1\--Meat Products (Excluding Quantity (thousands of Poultry) kilograms)\2\ ¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤ Canada 681,899 ------------------------------------------------------------------------ Australia 376,585 ------------------------------------------------------------------------ New Zealand 211,873 ------------------------------------------------------------------------ Uruguay 103,305 ------------------------------------------------------------------------ Brazil 83,897 ------------------------------------------------------------------------ Denmark 46,652 ------------------------------------------------------------------------ Mexico 35,553 ------------------------------------------------------------------------ China 28,530 ------------------------------------------------------------------------ Argentina 22,353 ------------------------------------------------------------------------ Nicaragua 21,303 ¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤ NAIC 311613--Animal Fats, Oils, & By- (thousands of Products kilograms)\3\ ¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤ Canada 94,306 ------------------------------------------------------------------------ New Zealand 32,550 ------------------------------------------------------------------------ China 7,809 ------------------------------------------------------------------------ Australia 6,807 ------------------------------------------------------------------------ Brazil 6,589 ------------------------------------------------------------------------ Mexico 2,130 ------------------------------------------------------------------------ Colombia 1,826 ------------------------------------------------------------------------ Germany 1,642 ------------------------------------------------------------------------ Ecuador 1,149 ------------------------------------------------------------------------ Japan 1,138 ------------------------------------------------------------------------ \1\ The NAIC code 31161 covers the animal slaughtering and processing industry. The industry is composed of establishments that are primarily engaged in one or more of the following: (1) Slaughtering animals, (2) preparing processed meats and meat by-products, and (3) rendering and refining animal fat, bones, and meat scraps. The subcategory 311611 comprises those establishments primarily engaged in slaughtering animals (except poultry and small game). Establishments that slaughter and prepare meats are included in this classification. (Ref. 5) We use this data as an indicator of the countries that are most likely to petition FDA regarding their BSE status. \2\ These figures do not include exports measured in ``clean yield kilograms'' and ``pieces.'' \3\ These figures do not include exports measured in ``grams,'' ``liters,'' ``metric tons,'' and ``pieces.''
We do not know how many countries might petition the FDA. However, taking into consideration the previous information on countries officially recognized as having a negligible BSE risk or being provisionally free of BSE under OIE, as well as the information in table 1 on countries that export large amounts of meat products and animal fats, oils, and byproducts to the United States, we are estimating for this analysis that 10 countries may be interested in petitioning FDA to be excepted from certain BSE-related restrictions applicable to human food and cosmetics. Our estimate is not intended to suggest that all of these countries would be able to qualify for a designation under Sec. Sec. 189.5(e) and 700.27(e). 3. Costs and Benefits of Exemption Provision
snip...$$$
http://edocket.access.gpo.gov/2008/08-1142.htm
http://edocket.access.gpo.gov/2008/pdf/08-1142.pdf
GWs BSE MRR policy, the legal trading of all strains of TSE globally $$$ DEATH FOR PROFIT, commodities and futures i.e. trade over human health and sound science, the exporting from the USA, all strains of TSE globally. ...tss
-------- Original Message -------- Subject: Docket No. 2004N-0081 and or RIN number RIN-0910-AF47 Use of Materials Derived From Cattle in Human Food and Cosmetics [comment submission] Date: Tue, 13 Jul 2004 16:08:38 -0500 From: "Terry S. Singeltary Sr." To: fdadockets@oc.fda.gov CC: burt.pritchett@fda.gov, Agriculture@mail.house.gov
COMMENT SUBMISSION [Docket No. 2004N-O081] RIN-0910--AF47 Use of Materials Derived From Cattle in Human Food and Cosmetics http://www.fda.gov/OHRMS/DOCKETS/98fr/04n-0081-nir0001.pdf
Greetings FDA,
I would kindly like to comment on the potential for TSE transmission from cosmetics to humans and why I think that ALL animal by-products should be excluded from cosmetics. IF we look at the TSE 'KURU'. Kuru is a transmissible spongiform encephalopathy that was identified in Papua New Guinea in the late 1950s. Several thousand cases of the disease occurred during a period of several decades. Epidemiologic investigations implicated ritual endocannibalistic funeral feasts as the likely route through which the infectious agent was spread. The incubation period in females was estimated to be shorter than that in males. The shortest incubation periods were estimated in adult women, who may have been exposed to the largest doses of infectious material. MY question is, was the woman exposed to larger doses, are was it the route of the agent that may have been the factor of shorter incubation in woman, or both?
What is Kuru? Kuru is a rare and fatal brain disorder that occurred at epidemic levels during the 1950s-60s among the Fore people in the highlands of New Guinea. The disease was the result of the practice of ritualistic cannibalism among the Fore, in which relatives prepared and consumed the tissues (including brain) of deceased family members. Brain tissue from individuals with kuru was highly infectious, and the disease was transmitted either through eating or by contact with open sores or wounds. Government discouragement of the practice of cannibalism led to a continuing decline in the disease, which has now mostly disappeared.
snip...
PLEASE NOTE the later ''or by contact with open sores or wounds.''
and the disease was transmitted either through eating or by contact with open sores or wounds.
http://www.ninds.nih.gov/health_and_medical/disorders/kuru.htm
the Fore women would scoop the brains of their dead relatives out of their skulls by hand before cooking. They then wiped the residual liquid and cadaver tissue over their paint-daubed bodies, leaving it caked in their hair and on their bodies for weeks after a mortuary feast.
Jennifer Cooke: kuru deaths continue in 1999
Sydney Morning Herald, Saturday, August 28, 1999
TSE INFECTION does takes place when the skin surface has been broken by scarification (Taylor et al, 1996).
The transmission of KURU into animals supported the belief that the disease had been transmitted through ceremonial cannibalistic rituals in New Guinea with a possible route of spread involving handling fresh tissue and inoculation through mucous membranes and wounds including skin abrasions (Gajdusek, 1977)
Masters, C.J., Gajdusek, D.C. and Gibbs, C.J., (1980). The spongiform encephalopathies: the natural history of CJD and its relationship to kuru and scrapie.
* Gajdusek D.C. (1996). Kuru: From the New Guinea field journals 1957-1962. Grand Street, 15:6-33
* Gajdusek D.C. (1973). Kuru in the New Guinea Highlands. In Spillane JD (ed): Tropical Neurology. New York, Oxford University Press.
* Gajdusek D.C., Gibbs C.J., and M. Alpers (1966). Experimental transmission of a kuru-like syndrome to chimpanzees. Nature, 209:794.
* Lindenbaum S. (1979). Kuru Sorcery. Mountain View, Ca, Mayfield Publishing Company.
SCCNFP/0724/03, final THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS OPINION CONCERNING USE OF SPECIFIED RISK MATERIAL IN COSMETICS CLARIFICATION FOR TALLOW DERIVATIVES adopted by the SCCNFP on 30 July 2003 by means of the written procedure SCCNFP/0724/03, final Opinion on the Use of specified risk material in cosmetics - Clarification for tallow derivatives _____________________________________________________________________________________________ 2 1. Background
snip...
http://europa.eu.int/comm/health/ph_risk/committees/sccp/documents/out229_en.pdf
4. For GBR-C III and IV countries, tallow derivatives are safe if, in addition to the above (3), the specific risk materials have been removed and are not used for the production of tallow/tallow derivatives.
PLEASE NOTE, under the old BSE GBR, the USA would be re-classified as at least a GBR III risk assessment, if not a GBR IV in my opinion due to the misgivings from USDA/APHIS et al, some documented below in my references from Docket No, 04-047-l Regulatory Identification No. (RIN) 091O-AF46 NEW BSE SAFEGUARDS (comment submission).
Report on the Assessment of the Geographical BSE - Risk of USA (July 2000) (220kb)
http://europa.eu.int/comm/food/fs/sc/ssc/out137_en.pdf
snip...end
-------- Original Message -------- Subject: Docket No, 04-047-l Regulatory Identification No. (RIN) 091O-AF46 NEW BSE SAFEGUARDS (comment submission) Date: Sun, 11 Jul 2004 21:34:22 -0500 From: "Terry S. Singeltary Sr." To: fdadockets@oc.fda.gov CC: regulations@aphis.usda.gov, burt.pritchett@fda.gov
Docket No. 04-047-l No. 04-021ANPR No. 2004N-0264 NEW BSE SAFEGUARDS Federal Measures to Mitigate BSE Risks: Considerations for Further Action http://www.fda.gov/cvm/index/updates/bseanprm.htm
Greetings FDA,
USDA and APHIS et al, I would kindly like to comment on the continued delay of the regulations that have been proposed for years to reduce the risk of BSE/TSE in the USA. Each day that is wasted debating this issue allows this agent to spread, and many many more humans and animals become needlessly exposed to this agent via a multitude of potential routes and sources right here in the USA. TO continue to ignore the new findings from several scientists about the fact that BSE is not the only strain of TSE in cattle, the fact that new atypical strains of TSE are showing up in not only cattle, but sheep and the fact that the new strain of TSE in cattle seems to be more similar to sporadic CJD as opposed to the nv/v CJD, to continue to ignore these findings will only further spread this agent. CWD and Scrapie have been running rampant in the USA for decades. BOTH of which have been rendered and fed back to animals for human/animal consumption for decades. All of which transmits to primates by the natural and non-forced oral consumption of TSE scrapie, CJD, Kuru agent (and CWD by inoculation). Strong Scientific evidence discovered back in the 80s support the fact that a TSE has been prevalent in the USA bovine for decades, either undetected or ignored. IF you consider the recent stumbling and staggering TEXAS cow that was showing all signs of a CNS/TSE disorder that was ordered to be rendered without BSE/TSE test, brains, spinal cord, head and all (as to no possible evidence left of TSE), I would think the 'ignored' or 'covered up' to be the better terminology. Then you have the Downer in Washington state that was actually a good walker and then all the banned Canadian products that some how found it's way across the border into the USA, considering all this, it is very difficult for me to believe that the FDA/USDA/APHIS et al are doing everything possible to protect the 'consumer'. Hardly the case;
Congressman Henry Waxmans Letter to the Honorable Ann Veneman
http://www.house.gov/reform/min/pdfs_108_2/pdfs_inves/pdf_food_usda_mad_cow_may_13_let.pdf
snip...
From: TSS () Subject: Re: Docket No. 2004N-0081 Use of Materials Derived From Cattle in Human Food and Cosmetics [TSS SUBMISSION] Date: September 7, 2005 at 7:35 pm PST
In Reply to: Docket No. 2004N-0081 Use of Materials Derived From Cattle in Human Food and Cosmetics posted by TSS on September 7, 2005 at 7:07 am:
----- Original Message ----- From: Terry S. Singeltary Sr. To: fdadockets@oc.fda.gov Sent: Wednesday, September 07, 2005 9:44 PM Subject: Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47
Greetings FDA,
I would kindly like to comment on ;
Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47
SUMMARY: The Food and Drug Administration (FDA) is amending the interim final rule on use of materials derived from cattle in human food and cosmetics published in the Federal Register of July 14, 2004. In the July 14, 2004, interim final rule, FDA designated certain materials from cattle, including the entire small intestine, as ``prohibited cattle materials'' and banned the use of such materials in human food, including dietary supplements, and in cosmetics. FDA is taking this action in response to comments received on the interim final rule. Information was provided in comments that persuaded the agency that the distal ileum, one of three portions of the small intestine, could be consistently and effectively removed from the small intestine, such that the remainder of the small intestine, formerly a prohibited cattle material, could be used for human food or cosmetics. We (FDA) are also clarifying that milk and milk products, hide and hide-derived products, and tallow derivatives are not prohibited cattle materials. Comments also led the agency to reconsider the method cited in the interim final rule for determining insoluble impurities in tallow and to cite instead a method that is less costly to use and requires less specialized equipment. FDA issued the interim final rule to minimize human exposure to materials that scientific studies have demonstrated are highly likely to contain the bovine spongiform encephalopathy (BSE) agent in cattle infected with the disease. FDA believes that the amended provisions of the interim final rule provide the same level of protection from human exposure to the agent that causes BSE as the original provisions. ...
I would kindly like to submit the following ;
I find it very very disturbing that FDA now takes the position;
Information was provided in comments that persuaded the agency that the distal ileum, one of three portions of the small intestine, could be consistently and effectively removed from the small intestine, such that the remainder of the small intestine, formerly a prohibited cattle material, could be used for human food or cosmetics.
<<< href="http://www.seac.gov.uk/statements/tonsil211002.pdf">http://www.seac.gov.uk/statements/tonsil211002.pdf<
UPDATE OF THE OPINION ON TSE INFECTIVITY DISTRIBUTION IN RUMINANT TISSUES INITIALLY ADOPTED BY THE SCIENTIFIC STEERING COMMITTEE AT ITS MEETING OF 10-11 JANUARY 2002 AND AMENDED AT ITS MEETING OF 7-8 NOVEMBER 2002
following the submission of (1) a risk assessment by the German Federal Ministry of Consumer Protection, food and Agriculture and (2) new scientific evidence regarding BSE infectivity distribution in tonsils
http://europa.eu.int/comm/food/fs/sc/ssc/out296_en.pdf
3. New work, work still in progress and future work The infectivity of neural and non-neural tissues by intracerebral inoculation of cattle is being assayed in projects M03006 and M03007. These studies are important since it is possible that some tissues may not yet have been found to be infective, due to the fact that infectivity in these tissues is below the detection limits of the tests applied so far. To date, this study has shown infectivity in CNS tissues, the distal ileum, tonsil tissue and the nictitating membrane (the nictitating membrane is also known as the third eyelid). Other challenged and control cattle continue to be closely monitored for clinical signs of BSE. Research is ongoing to determine the susceptibility of other food animal species to TSEs. These include a project to determine the susceptibility of pigs to scrapie through oral exposure (M03005) and a project to further study the transmission of BSE to pigs (M03010). Project M03024 aims to determine whether UK red deer are susceptible to BSE by oral exposure. These studies are important since it is highly probable that pigs and deer were historically exposed to ruminant derived meat and bone meal (MBM). ...
http://www.food.gov.uk/multimedia/pdfs/annualresearchrpt04.pdf
TSEs And The Environment
The LANCET
Volume 351, Number 9110 18 April 1998 BSE: the final resting place
snip...
The first matter to consider is the distribution of infectivity in the bodies of infected animals. The brain (and more generally, the central nervous system) is the primary target in all transmissible spongiform encephalopathies (TSE), and it contains by far the highest concentration of the infectious agent. In naturally occuring disease, infectivity may reach levels of up to about one million lethal doses per gram of brain tissue, whether the disease be kuru, CJD, scrapie, or BSE. The infectious agent in BSE-infected cattle has so far been found only in brain, spinal cord, cervical and thoracic dorsal root ganglia, trigeminal ganglia, distal ileum, and bone marrow.4 However, the much more widespread distribution of low levels of infectivity in human beings with kuru or CJD, and in sheep and goats with scrapie, suggests that caution is advisable in prematurely dismissing as harmless other tissues of BSE-infected cattle. snip...end...TSS snip... BY reducing or weakening the SRM list due to the Economic Impact of BSE on the U.S. Beef Industry and while doing so, ignoring all 'sound science', again the FDA/USDA et al are willing to put every human and animal out there at risk to further exposure to this TSE agent, all for a buck. this is not 'sound science' this is what i call 'corporate science', and it is and will continue to expose people. some of these people will die from this agent either directly or indirectly via a multitude of scientific proven routes and sources. WE must remove all political and corporate science from TSE research. I find it disturbing that products that carry SRMs are still on the market for humans such as nutritional supplements ;
ODD, I just picked up a catalog from STANDARD PROCESS INC. 2003 - 2004 Product Catalog (a chiropractor had just left this catalog in my wife's foot doctors office 4/5/05) and it's full of THOSE SRMS FOR HUMANS. I wonder how much is still left on the market, and how much is still in production, how much crosses the borders? 5 pages of products full of SRMs for humans. THIS is a really fine catalog, i am just now going over. LOADED with SRMs for humans. NO wonder my neighbors mom died from CJD while taking these damn mad cow pills. THEY even have a candy bars loaded with SRMs.
HERE is one ;
NATURAL COCOA STANDARDBAR (mad cow candy bar) (i will just list animal organs) bovine adrenal, bovine liver, bovine spleen, ovine spleen, bovine kidney...
NATURAL PEANUT BUTTER STANDARDBAR bovine adrenal, bovine liver, bovine spleen, ovine spleen, bovine kidney...
USF (MAD COW) OINTMENT (RUB A DUB DUB, KURU ETC) ; bovine orhic glandular extract UTROPHIN PMG bovine uterus PMG VASCULIN bovine heart PMG extract, veal bone PMG extract, bovine liever, porcine duodenum, bovine adrenal Cytosol extract, bovine spleen, ovine spleen (some yummy stuff)
IPLEX (neighbors mom died from CJD while taking these pills for years) bovine eye PMG extract, veal bone PMG, bovine liver, porcine stomach, bovine adrenal, bovine kidney, bovine adrenal Cytosol extract, BOVINE BRAIN, bovine bone, veal bone meal MYO-PLUS bovine heart PMG, bovine liver, porcine stomach, bovine orchic extract, bovine spleen, ovine spleen, bovine adrenal Cytosol extract,
BOVINE BRAIN NEUROPLEX bovine orchic Cytosol extract, bovine spleen, BOVINE BRAIN PMG EXTRACT, BOVINE ANTERIOR PITUITARY, bovine liver, BOVINE PITUITARY PMG EXTRACT, AND MORE BOVINE BRAIN...
HOLY MAD COW IN A PILL !!! NEUROTROPHIN PMG BOVINE BRAIN PMG NIACINAMIDE B6 VM bovine liver, porcine stomach, bovine spleen ovine spleen, BOVINE BRAIN OCULOTROPHIN PMG BOVINE EYE PMG ORCHEX bovine liver, bovine orchic Cytosol extract, porcine stomch, bovine spleen, ovine spleen, BOVINE BRAIN OSTARPLEX veal bone PMG extract, veal bone PMG extract, bovine liver, porcine stomach, bovine adrenal, bovine spleen, ovine spleen, BOVINE BRAIN PARAPLEX bovine pancreas PMG extract, porcine duodenum, bovine adrenal PMG, BOVINE PITUITARY PMG EXTRACT, bovine thyroid PMG extract PITUITROPHIN PMG RUMAPLEX BOVINE BRAIN, veal bone PMG extract, bovine adrenal, bovine prostate Cytosol extract, veal bone meal, bovine liver PMG extract, bovine spleen, ovine spleen, bovine liver SENAPLEX bovine liver PMG extract, bovine adrenal, BOVNE BRAIN, veal bone meal, bovine kidney, bovine orchic extract, bovine spleen, ovine spleen ..........
THESE are just a few of MANY of just this ONE COMPANY.
Docket Management Docket: 96N-0417 - Current Good Manufacturing Practice in Manufacturing, Packing, or Holding Dietary Ingredients a Comment Number: EC -2 Accepted - Volume 7 253 1
DR. BOLTON: I have an additional question about 2 that. What is the assurance that additional locally sourced 3 tracheas are not added into that manufacturing process, thus 4 boosting the yield, if you will, but being returned to the 5 U.S. as being produced from U.S.-sourced raw material? 6 DR. McCURDY: Are there data to indicate how many 7 grams, or whatever, of infected brain are likely to infect 8 an organism, either animal or man, when taken orally? 9 DR. BROWN: If I am not mistaken, and I can be 10 corrected, I think a half a gram is enough in a cow, orally; 11 in other words, one good dietary-supplement pill. 12 DR. McCURDY: What I am driving at is the question 13 we are asked is really not do we wish to regulate these 14 things coming in. I think the statements about difficulties 15 in regulating things in the future or near future for new 16 regulations were probably accurate. 17 But I think that we could exhibit some quite 18 reasonable concern about blood donors who are taking dietary 19 supplements that contain a certain amount of unspecified- 20 origin brain, brain-related, brain and pituitary material. 21 If they have done this for more than a sniff or something 22 like that, then, perhaps, they should be deferred as blood 23 donors. 24 That is probably worse than spending six months in 25 the U.K. 254 1 DR. BROWN: That is exactly right. I think that 2 is why the discussion has apparently been on things that are 3 not directly related to these questions because, in order to 4 think about deferrals for blood donors who are taking 5 dietary supplements with things like bovine brain in them, 6 it is very important that we know that those products are 7 safe. 8 I think we have heard enough to suggest that they 9 may not be. 10 DR. McCURDY: There is one other item that needs 11 to be considered and that is what proportion of blood donors 12 are doing this; that is, how many blood donors would you 13 lose, and I don't know what the demographics--there is 14 fairly good information on the demography of blood donors. 15 I have no idea what the demography of people who take these 16 supplements is. Maybe they are old men like me and aren't 17 going to be blood donors anymore. 18 DR. BROWN: The wording of the question is not as 19 demanding as the wording of other deferral questions; that 20 is, the question here is consider recommending. We are 21 not even recommending at this point. We are saying to the 22 FDA, please think about this. It is worth thinking about. 23 DR. DETWILER: One point about brain from Europe, 24 and Jean Philippe is still here, those are considered 25 specified risk material and it is not correct to be 255 1 incinerated; correct? Or destroyed? Brain and spinal cord 2 and other high-risk tissues in Europe? 3 DR. NORTON: In tomorrow morning's British Medical 4 Journal, which has appeared on-line today, there is an 5 article called U.S. Takes Precautions against BSE. One 6 paragraph says, Even though the U.S. and U.K. governments 7 ban the practice of feeding cattle products to cows, in the 8 early 1990s, some U.K. renderers continued to manufacture 9 and ship contaminated meat and bonemeal around the world. 10 British export statistics show that thirty-seven tons of 11 meal made from offal was sent to the United States in 1997, 12 well after the U.S. government banned imports of such risky 13 meat. The ultimate use of these imports has not been 14 identified. 15 That will appear tomorrow morning. 16 DR. DETWILER: That actually was in The New York 17 Times. That is a direct quote out of The New York Times 18 article. We called the reporter on that. That statement, 19 the thirty-seven tons, was taken out of the U.S. 20 Geographical BSE Risk Assessment. What they didn't put in 21 there, in the statement, was the remainder of the GBR is at 22 that time, the big labeling for that category in the U.K., 23 because it was illegal for them to ship it to us from their 24 own regs. It is illegal for us to get that. 25 We did go and try and trace that so that wasn't
[FULL TEXT ABOUT 600 PAGES] 3681t2.rtf
http://www.fda.gov/ohrms/dockets/ac/cber01.htm
http://www.fda.gov/ohrms/dockets/dailys/03/Mar03/031403/96N-0417-EC-2.htm
IN fact, we are now finding that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of the cows to come down with BSE ; Published online January 27, 2005 Risk of oral infection with bovine spongiform encephalopathy agent in primates Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)—which can lead to variant Creutzfeldt-Jakob disease (vCJD)—is compounded by incomplete knowledge about the ef.ciency of oral infection and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the other remained free of disease at 76 months. On the basis of these .ndings and data from other studies, we made a preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public health measures can prevent transmission of BSE to man. snip...
BSE bovine brain inoculum 100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg Primate (oral route)* 1/2 (50%) Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%) RIII mice (icip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%) PrPres biochemical detection
The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the .rst positive animal (%). The accuracy of bioassays is generally judged to be about plus or minus 1 log. icip=intracerebral and intraperitoneal. Table 1: Comparison of transmission rates in primates and cattle infected orally with similar BSE brain inocula snip...end www.thelancet.com Published online January 27, 2005 THEN you must consider cross contamination at feed mills and such. this has been well proven in both the UK and the USA to date via r-to-r feed ban violations. IT was proven in the UK that they indeed put profits before human health; [PDF]
The BSE Inquiry / Statement No. 14 Issued 20 March 1998 THE ...
The BSE Inquiry / Statement No. 14. Issued 20 March 1998 ...
number of feed compounders and it became clear that cross contamination of feeds could occur. ...
http://www.bseinquiry.gov.uk/files/ws/s014.pdf
[PDF] The BSE Inquiry / Statement No 76F (Supplementary) Mr Alan ... But the mainbut the main problem was probably cross-contamination. ...
http://www.bseinquiry.gov.uk/files/ws/s076f.pdf
STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995
snip...
To minimise the risk of farmers' claims for compensation from feed compounders. To minimise the potential damage to compound feed markets through adverse publicity. To maximise freedom of action for feed compounders, notably by maintaining the availability of meat and bone meal as a raw material in animal feeds, and ensuring time is available to make any changes which may be required.
snip...
THE FUTURE 4..........
MAFF remains under pressure in Brussels and is not skilled at handling potentially explosive issues. 5. Tests _may_ show that ruminant feeds have been sold which contain illegal traces of ruminant protein. More likely, a few positive test results will turn up but proof that a particular feed mill knowingly supplied it to a particular farm will be difficult if not impossible. 6. The threat remains real and it will be some years before feed compounders are free of it. The longer we can avoid any direct linkage between feed milling _practices_ and actual BSE cases, the more likely it is that serious damage can be avoided. ...
SEE full text ;
http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf
snip...
From: TSS Subject: Inspector to file charges against USDA for them charging him with misconduct on telling the truth about SRM mad cow violations Date: September 7, 2005 at 1:37 pm PST
Consumer Health Inspector to file charges against USDA
By Steve Mitchell Sep 6, 2005, 22:46 GMT WASHINGTON, DC, United States (UPI) --
The federal meat inspector who was charged with misconduct by the U.S. Department of Agriculture after he claimed mad cow disease safeguards were being violated at slaughterhouses told United Press International he plans to file charges against the agency. Stan Painter, a USDA inspector and chair of the National Joint Council of Food Inspection Locals, the inspectors union, notified the agency`s management in a letter last December he was aware of instances where the riskiest parts of older cows were not being marked or removed from processing. Painter worried these risky parts -- known as specified risk materials, or SRMs -- could enter the food supply and infect people, causing a fatal brain illness called variant Creutzfeldt Jakob disease. Two cases of mad cow have been detected in U.S. herds, and some suspect there are more. The USDA put the SRM safeguards in place in 2004 to protect the public from mad cow disease -- also known as bovine spongiform encephalopathy or BSE -- if more cases are detected. The USDA did not respond to Painter`s concerns until he made his letter known to news outlets. On Dec. 28, 2004, the agency charged Painter with personal misconduct for not revealing the names of the inspectors who told him of the SRM violations. Officials also told him he was under a formal investigation, which was dropped last month after the release of internal documents revealing more than 1,000 violations of the USDA`s SRM regulations. Painter said he thinks the USDA was attempting 'to harass and intimidate him (and) to have a chilling effect' on other inspectors. 'I plan to file charges against the agency,' he told UPI, adding he has not yet decided if he will go through the legal system, through internal USDA procedures or another avenue. Asked about Painter`s intent to bring charges, agency spokesman Steven Cohen told UPI the documents -- called noncompliance reports, or NRs -- demonstrate 'that BSE safeguard regulations are being enforced and prohibited materials did not reach the public.' Mad cow disease remains a sensitive topic for the USDA because it can have significant economic ramifications. The U.S. beef industry lost billions of dollars because more than 60 nations closed their borders in 2003 to American beef after the report of the first detected case in U.S. herds. Japan, formerly the largest importer of American beef, still has not reopened its borders. For months, USDA officials denied Painter`s allegations in media reports, saying they had investigated and found no evidence to substantiate his claims. The NRs released last month under the Freedom of Information Act, however, showed 1,036 violations of SRM regulations in at least 35 states, Puerto Rico and the Virgin Islands, with some plants being cited repeatedly for infractions. The USDA delayed releasing the documents for eight months despite a federal law mandating a response within 30 days. Patty Lovera, of the watchdog group Public Citizen, which requested the USDA documents, said some of the violations cited in the NRs are egregious. In one, an employee at a plant in Michigan was not properly marking older cows to have their SRMs removed because he did not have a pencil. In another, an employee in a Missouri plant was loading cow heads onto his pickup truck to take home to feed to his dog. Lovera charged the USDA with attempting to silence Painter and failing to address problems with the SRM ban. 'Their behavior through this whole thing is appalling,' she told UPI. 'Stan brought them concerns about a policy and instead of investigating the policy, they investigated him.' Last December, after Painter made his letter known publicly, the USDA sent an officer to Painter`s house while he was on leave to question him about the allegations in his letter. Later, USDA officials interrogated Painter twice, asking him for the names of the inspectors who told him about the violations. Painter said he intentionally was kept ignorant of the inspectors` names because he feared the agency would retaliate against them. Painter also said USDA officials did ot need the inspectors` names because they could determine where the infractions were occurring by looking at their database of NRs. Sometime around June the U.S. Embassy in Japan posted a notice on its Web site stating USDA officials had found no evidence to substantiate Painter`s claims and had requested a criminal investigation into his actions. The notice was removed in July after UPI reported its existence. Although Cohen acknowledged more than 1,000 NRs were written by USDA inspectors, he minimized their significance, saying they 'amount to less than one-half of one percent of the total written for all reasons by (USDA) inspection program personnel.' Lovera said any infraction of mad cow safeguards should be of concern, because this disease always is fatal in humans and cooking does not destroy the pathogen. 'You have very little margin of error for something you don`t want to get because you can`t cook it away and you can`t disinfect it,' she said. Painter said his concern now is what the agency will do to fix what he sees as shortcomings in the SRM policy. 'It`s a failed policy,' he said. 'It doesn`t protect the consumer.' Cohen did not respond to whether the USDA planned to change the SRM regulations. The USDA`s Office of Inspector General has launched an investigation to determine whether the regulations are being implemented effectively, and results are due out soon.
E-mail: sciencemail@upi.com Copyright 2005 by United Press International
http://washingtontimes.com/upi/20050906-050340-6793r.htm
*** makes no difference, GW will change the SRM rules like he has the BSE GBR risk assessment to the terribly flawed BSE MRR policy, the legal trading of all strains of TSE, the 'gold card'. ...TSS
IN a time when FDA/USDA et al should be strengthening the TSE regulations, it seems corporate interest has won out again over sound science and consumer protection from an agent that is 100% fatal for the ones that go clinical. With the many different atypical TSEs showing up in different parts of the world, and with GWs BSE MRR policy (the legal policy of trading all strains of TSEs), the battle that has waged for the last 25 years to eradicate this agent from this planet will be set back decades, if not lost for good. ...TSS
snip...
http://www.fda.gov/ohrms/dockets/dailys/03/Mar03/031403/96N-0417-EC-2.htm
http://www.fas.usda.gov/info/fr/2004/071404BSEFDA1.htm
http://www.fda.gov/ohrms/DOCKETS/dockets/04n0081/04n-0081-ref0001-Tab-A-vol6.pdf
APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15, 2006
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle 9/13/2005
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 [Federal Register: January 9, 2007 (Volume 72, Number 5)] [Proposed Rules] [Page 1101-1129] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr09ja07-21]
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f8152
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 Date: January 9, 2007 at 9:08 am PST
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f3412
Sunday, March 16, 2008 MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html
SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE
http://downercattle.blogspot.com/
SRM MAD COW RECALL 406 THOUSAND POUNDS CATTLE HEADS WITH TONSILS KANSAS
http://cjdmadcowbaseoct2007.blogspot.com/2008/04/srm-mad-cow-recall-406-thousand-pounds.html
SPECIFIED RISK MATERIALS
http://madcowspontaneousnot.blogspot.com/2008/02/specified-risk-materials-srm.html
CJD USA
*Acquired in UK ** Acquired in Saudi Arabia *** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007. **** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26 from 2007). Notes: -- Cases are listed based on the year of death when available. If the year of death is not available, the year of sample receipt is used. -- Referrals: Cases with possible or probable prion disease from which brain tissue or blood in the case of familial disease were submitted. -- Inconclusive: Cases in which the samples were not sufficient to make a diagnosis. -- Non-vCJD type unknown are cases in which the tissue submitted was adequate to establish the presence but not the type; in all cases, vCJD could be excluded. -- Communicated by: Terry S. Singeltary Sr.
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.
He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
ALL animals for human/animal consumption must be tested for TSE.
ALL human TSEs must be made reportable Nationally and Internationally, OF ALL AGES. ...TSS
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
======================================================================= -----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 189 and 700
[Docket No. 2004N-0081] RIN 0910-AF47
Use of Materials Derived From Cattle in Human Food and Cosmetics
AGENCY: Food and Drug Administration, HHS.
ACTION: Interim final rule and request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is amending its regulations on the use of materials derived from cattle in human food and cosmetics. In these regulations, FDA has designated certain materials from cattle as ``prohibited cattle materials'' and has banned the use of such materials in human food, including dietary supplements, and in cosmetics. Prohibited cattle materials include specified risk materials (SRMs), the small intestine of all cattle unless the distal ileum is removed, material from nonambulatory disabled cattle, material from cattle not inspected and passed for human consumption, or mechanically separated (MS) (Beef). Specified risk materials include the brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia of cattle 30 months of age and older, and the tonsils and distal ileum of the small intestine of all cattle. FDA is amending its regulations so that FDA may designate a country as not subject to certain bovine spongiform encephalopathy (BSE)-related restrictions applicable to FDA regulated human food and cosmetics. A country seeking to be so designated must send a written request to the Director of FDA's Center for Food Safety and Applied Nutrition, including information about the country's BSE case history, risk factors, measures to prevent the introduction and transmission of BSE, and any other relevant information.
DATES: This interim final rule is effective July 16, 2008. Submit written or electronic comments on this interim final rule by July 16, 2008. Submit comments on information collection issues under the Paperwork Reduction Act of 1995 by May 19, 2008 (see the ``Paperwork Reduction Act of 1995'' section of this document).
snip...
Table 1.--Top 10 Countries Exporting Specified North American Industry Classification System (NAICS) Code Products to United States for 2006 NAICS 311611\1\--Meat Products (Excluding Quantity (thousands of Poultry) kilograms)\2\ ¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤ Canada 681,899 ------------------------------------------------------------------------ Australia 376,585 ------------------------------------------------------------------------ New Zealand 211,873 ------------------------------------------------------------------------ Uruguay 103,305 ------------------------------------------------------------------------ Brazil 83,897 ------------------------------------------------------------------------ Denmark 46,652 ------------------------------------------------------------------------ Mexico 35,553 ------------------------------------------------------------------------ China 28,530 ------------------------------------------------------------------------ Argentina 22,353 ------------------------------------------------------------------------ Nicaragua 21,303 ¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤ NAIC 311613--Animal Fats, Oils, & By- (thousands of Products kilograms)\3\ ¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤ Canada 94,306 ------------------------------------------------------------------------ New Zealand 32,550 ------------------------------------------------------------------------ China 7,809 ------------------------------------------------------------------------ Australia 6,807 ------------------------------------------------------------------------ Brazil 6,589 ------------------------------------------------------------------------ Mexico 2,130 ------------------------------------------------------------------------ Colombia 1,826 ------------------------------------------------------------------------ Germany 1,642 ------------------------------------------------------------------------ Ecuador 1,149 ------------------------------------------------------------------------ Japan 1,138 ------------------------------------------------------------------------ \1\ The NAIC code 31161 covers the animal slaughtering and processing industry. The industry is composed of establishments that are primarily engaged in one or more of the following: (1) Slaughtering animals, (2) preparing processed meats and meat by-products, and (3) rendering and refining animal fat, bones, and meat scraps. The subcategory 311611 comprises those establishments primarily engaged in slaughtering animals (except poultry and small game). Establishments that slaughter and prepare meats are included in this classification. (Ref. 5) We use this data as an indicator of the countries that are most likely to petition FDA regarding their BSE status. \2\ These figures do not include exports measured in ``clean yield kilograms'' and ``pieces.'' \3\ These figures do not include exports measured in ``grams,'' ``liters,'' ``metric tons,'' and ``pieces.''
We do not know how many countries might petition the FDA. However, taking into consideration the previous information on countries officially recognized as having a negligible BSE risk or being provisionally free of BSE under OIE, as well as the information in table 1 on countries that export large amounts of meat products and animal fats, oils, and byproducts to the United States, we are estimating for this analysis that 10 countries may be interested in petitioning FDA to be excepted from certain BSE-related restrictions applicable to human food and cosmetics. Our estimate is not intended to suggest that all of these countries would be able to qualify for a designation under Sec. Sec. 189.5(e) and 700.27(e). 3. Costs and Benefits of Exemption Provision
snip...$$$
http://edocket.access.gpo.gov/2008/08-1142.htm
http://edocket.access.gpo.gov/2008/pdf/08-1142.pdf
GWs BSE MRR policy, the legal trading of all strains of TSE globally $$$ DEATH FOR PROFIT, commodities and futures i.e. trade over human health and sound science, the exporting from the USA, all strains of TSE globally. ...tss
-------- Original Message -------- Subject: Docket No. 2004N-0081 and or RIN number RIN-0910-AF47 Use of Materials Derived From Cattle in Human Food and Cosmetics [comment submission] Date: Tue, 13 Jul 2004 16:08:38 -0500 From: "Terry S. Singeltary Sr." To: fdadockets@oc.fda.gov CC: burt.pritchett@fda.gov, Agriculture@mail.house.gov
COMMENT SUBMISSION [Docket No. 2004N-O081] RIN-0910--AF47 Use of Materials Derived From Cattle in Human Food and Cosmetics http://www.fda.gov/OHRMS/DOCKETS/98fr/04n-0081-nir0001.pdf
Greetings FDA,
I would kindly like to comment on the potential for TSE transmission from cosmetics to humans and why I think that ALL animal by-products should be excluded from cosmetics. IF we look at the TSE 'KURU'. Kuru is a transmissible spongiform encephalopathy that was identified in Papua New Guinea in the late 1950s. Several thousand cases of the disease occurred during a period of several decades. Epidemiologic investigations implicated ritual endocannibalistic funeral feasts as the likely route through which the infectious agent was spread. The incubation period in females was estimated to be shorter than that in males. The shortest incubation periods were estimated in adult women, who may have been exposed to the largest doses of infectious material. MY question is, was the woman exposed to larger doses, are was it the route of the agent that may have been the factor of shorter incubation in woman, or both?
What is Kuru? Kuru is a rare and fatal brain disorder that occurred at epidemic levels during the 1950s-60s among the Fore people in the highlands of New Guinea. The disease was the result of the practice of ritualistic cannibalism among the Fore, in which relatives prepared and consumed the tissues (including brain) of deceased family members. Brain tissue from individuals with kuru was highly infectious, and the disease was transmitted either through eating or by contact with open sores or wounds. Government discouragement of the practice of cannibalism led to a continuing decline in the disease, which has now mostly disappeared.
snip...
PLEASE NOTE the later ''or by contact with open sores or wounds.''
and the disease was transmitted either through eating or by contact with open sores or wounds.
http://www.ninds.nih.gov/health_and_medical/disorders/kuru.htm
the Fore women would scoop the brains of their dead relatives out of their skulls by hand before cooking. They then wiped the residual liquid and cadaver tissue over their paint-daubed bodies, leaving it caked in their hair and on their bodies for weeks after a mortuary feast.
Jennifer Cooke: kuru deaths continue in 1999
Sydney Morning Herald, Saturday, August 28, 1999
TSE INFECTION does takes place when the skin surface has been broken by scarification (Taylor et al, 1996).
The transmission of KURU into animals supported the belief that the disease had been transmitted through ceremonial cannibalistic rituals in New Guinea with a possible route of spread involving handling fresh tissue and inoculation through mucous membranes and wounds including skin abrasions (Gajdusek, 1977)
Masters, C.J., Gajdusek, D.C. and Gibbs, C.J., (1980). The spongiform encephalopathies: the natural history of CJD and its relationship to kuru and scrapie.
* Gajdusek D.C. (1996). Kuru: From the New Guinea field journals 1957-1962. Grand Street, 15:6-33
* Gajdusek D.C. (1973). Kuru in the New Guinea Highlands. In Spillane JD (ed): Tropical Neurology. New York, Oxford University Press.
* Gajdusek D.C., Gibbs C.J., and M. Alpers (1966). Experimental transmission of a kuru-like syndrome to chimpanzees. Nature, 209:794.
* Lindenbaum S. (1979). Kuru Sorcery. Mountain View, Ca, Mayfield Publishing Company.
SCCNFP/0724/03, final THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS OPINION CONCERNING USE OF SPECIFIED RISK MATERIAL IN COSMETICS CLARIFICATION FOR TALLOW DERIVATIVES adopted by the SCCNFP on 30 July 2003 by means of the written procedure SCCNFP/0724/03, final Opinion on the Use of specified risk material in cosmetics - Clarification for tallow derivatives _____________________________________________________________________________________________ 2 1. Background
snip...
http://europa.eu.int/comm/health/ph_risk/committees/sccp/documents/out229_en.pdf
4. For GBR-C III and IV countries, tallow derivatives are safe if, in addition to the above (3), the specific risk materials have been removed and are not used for the production of tallow/tallow derivatives.
PLEASE NOTE, under the old BSE GBR, the USA would be re-classified as at least a GBR III risk assessment, if not a GBR IV in my opinion due to the misgivings from USDA/APHIS et al, some documented below in my references from Docket No, 04-047-l Regulatory Identification No. (RIN) 091O-AF46 NEW BSE SAFEGUARDS (comment submission).
Report on the Assessment of the Geographical BSE - Risk of USA (July 2000) (220kb)
http://europa.eu.int/comm/food/fs/sc/ssc/out137_en.pdf
snip...end
-------- Original Message -------- Subject: Docket No, 04-047-l Regulatory Identification No. (RIN) 091O-AF46 NEW BSE SAFEGUARDS (comment submission) Date: Sun, 11 Jul 2004 21:34:22 -0500 From: "Terry S. Singeltary Sr." To: fdadockets@oc.fda.gov CC: regulations@aphis.usda.gov, burt.pritchett@fda.gov
Docket No. 04-047-l No. 04-021ANPR No. 2004N-0264 NEW BSE SAFEGUARDS Federal Measures to Mitigate BSE Risks: Considerations for Further Action http://www.fda.gov/cvm/index/updates/bseanprm.htm
Greetings FDA,
USDA and APHIS et al, I would kindly like to comment on the continued delay of the regulations that have been proposed for years to reduce the risk of BSE/TSE in the USA. Each day that is wasted debating this issue allows this agent to spread, and many many more humans and animals become needlessly exposed to this agent via a multitude of potential routes and sources right here in the USA. TO continue to ignore the new findings from several scientists about the fact that BSE is not the only strain of TSE in cattle, the fact that new atypical strains of TSE are showing up in not only cattle, but sheep and the fact that the new strain of TSE in cattle seems to be more similar to sporadic CJD as opposed to the nv/v CJD, to continue to ignore these findings will only further spread this agent. CWD and Scrapie have been running rampant in the USA for decades. BOTH of which have been rendered and fed back to animals for human/animal consumption for decades. All of which transmits to primates by the natural and non-forced oral consumption of TSE scrapie, CJD, Kuru agent (and CWD by inoculation). Strong Scientific evidence discovered back in the 80s support the fact that a TSE has been prevalent in the USA bovine for decades, either undetected or ignored. IF you consider the recent stumbling and staggering TEXAS cow that was showing all signs of a CNS/TSE disorder that was ordered to be rendered without BSE/TSE test, brains, spinal cord, head and all (as to no possible evidence left of TSE), I would think the 'ignored' or 'covered up' to be the better terminology. Then you have the Downer in Washington state that was actually a good walker and then all the banned Canadian products that some how found it's way across the border into the USA, considering all this, it is very difficult for me to believe that the FDA/USDA/APHIS et al are doing everything possible to protect the 'consumer'. Hardly the case;
Congressman Henry Waxmans Letter to the Honorable Ann Veneman
http://www.house.gov/reform/min/pdfs_108_2/pdfs_inves/pdf_food_usda_mad_cow_may_13_let.pdf
snip...
From: TSS () Subject: Re: Docket No. 2004N-0081 Use of Materials Derived From Cattle in Human Food and Cosmetics [TSS SUBMISSION] Date: September 7, 2005 at 7:35 pm PST
In Reply to: Docket No. 2004N-0081 Use of Materials Derived From Cattle in Human Food and Cosmetics posted by TSS on September 7, 2005 at 7:07 am:
----- Original Message ----- From: Terry S. Singeltary Sr. To: fdadockets@oc.fda.gov Sent: Wednesday, September 07, 2005 9:44 PM Subject: Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47
Greetings FDA,
I would kindly like to comment on ;
Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47
SUMMARY: The Food and Drug Administration (FDA) is amending the interim final rule on use of materials derived from cattle in human food and cosmetics published in the Federal Register of July 14, 2004. In the July 14, 2004, interim final rule, FDA designated certain materials from cattle, including the entire small intestine, as ``prohibited cattle materials'' and banned the use of such materials in human food, including dietary supplements, and in cosmetics. FDA is taking this action in response to comments received on the interim final rule. Information was provided in comments that persuaded the agency that the distal ileum, one of three portions of the small intestine, could be consistently and effectively removed from the small intestine, such that the remainder of the small intestine, formerly a prohibited cattle material, could be used for human food or cosmetics. We (FDA) are also clarifying that milk and milk products, hide and hide-derived products, and tallow derivatives are not prohibited cattle materials. Comments also led the agency to reconsider the method cited in the interim final rule for determining insoluble impurities in tallow and to cite instead a method that is less costly to use and requires less specialized equipment. FDA issued the interim final rule to minimize human exposure to materials that scientific studies have demonstrated are highly likely to contain the bovine spongiform encephalopathy (BSE) agent in cattle infected with the disease. FDA believes that the amended provisions of the interim final rule provide the same level of protection from human exposure to the agent that causes BSE as the original provisions. ...
I would kindly like to submit the following ;
I find it very very disturbing that FDA now takes the position;
Information was provided in comments that persuaded the agency that the distal ileum, one of three portions of the small intestine, could be consistently and effectively removed from the small intestine, such that the remainder of the small intestine, formerly a prohibited cattle material, could be used for human food or cosmetics.
<<< href="http://www.seac.gov.uk/statements/tonsil211002.pdf">http://www.seac.gov.uk/statements/tonsil211002.pdf<
UPDATE OF THE OPINION ON TSE INFECTIVITY DISTRIBUTION IN RUMINANT TISSUES INITIALLY ADOPTED BY THE SCIENTIFIC STEERING COMMITTEE AT ITS MEETING OF 10-11 JANUARY 2002 AND AMENDED AT ITS MEETING OF 7-8 NOVEMBER 2002
following the submission of (1) a risk assessment by the German Federal Ministry of Consumer Protection, food and Agriculture and (2) new scientific evidence regarding BSE infectivity distribution in tonsils
http://europa.eu.int/comm/food/fs/sc/ssc/out296_en.pdf
3. New work, work still in progress and future work The infectivity of neural and non-neural tissues by intracerebral inoculation of cattle is being assayed in projects M03006 and M03007. These studies are important since it is possible that some tissues may not yet have been found to be infective, due to the fact that infectivity in these tissues is below the detection limits of the tests applied so far. To date, this study has shown infectivity in CNS tissues, the distal ileum, tonsil tissue and the nictitating membrane (the nictitating membrane is also known as the third eyelid). Other challenged and control cattle continue to be closely monitored for clinical signs of BSE. Research is ongoing to determine the susceptibility of other food animal species to TSEs. These include a project to determine the susceptibility of pigs to scrapie through oral exposure (M03005) and a project to further study the transmission of BSE to pigs (M03010). Project M03024 aims to determine whether UK red deer are susceptible to BSE by oral exposure. These studies are important since it is highly probable that pigs and deer were historically exposed to ruminant derived meat and bone meal (MBM). ...
http://www.food.gov.uk/multimedia/pdfs/annualresearchrpt04.pdf
TSEs And The Environment
The LANCET
Volume 351, Number 9110 18 April 1998 BSE: the final resting place
snip...
The first matter to consider is the distribution of infectivity in the bodies of infected animals. The brain (and more generally, the central nervous system) is the primary target in all transmissible spongiform encephalopathies (TSE), and it contains by far the highest concentration of the infectious agent. In naturally occuring disease, infectivity may reach levels of up to about one million lethal doses per gram of brain tissue, whether the disease be kuru, CJD, scrapie, or BSE. The infectious agent in BSE-infected cattle has so far been found only in brain, spinal cord, cervical and thoracic dorsal root ganglia, trigeminal ganglia, distal ileum, and bone marrow.4 However, the much more widespread distribution of low levels of infectivity in human beings with kuru or CJD, and in sheep and goats with scrapie, suggests that caution is advisable in prematurely dismissing as harmless other tissues of BSE-infected cattle. snip...end...TSS snip... BY reducing or weakening the SRM list due to the Economic Impact of BSE on the U.S. Beef Industry and while doing so, ignoring all 'sound science', again the FDA/USDA et al are willing to put every human and animal out there at risk to further exposure to this TSE agent, all for a buck. this is not 'sound science' this is what i call 'corporate science', and it is and will continue to expose people. some of these people will die from this agent either directly or indirectly via a multitude of scientific proven routes and sources. WE must remove all political and corporate science from TSE research. I find it disturbing that products that carry SRMs are still on the market for humans such as nutritional supplements ;
ODD, I just picked up a catalog from STANDARD PROCESS INC. 2003 - 2004 Product Catalog (a chiropractor had just left this catalog in my wife's foot doctors office 4/5/05) and it's full of THOSE SRMS FOR HUMANS. I wonder how much is still left on the market, and how much is still in production, how much crosses the borders? 5 pages of products full of SRMs for humans. THIS is a really fine catalog, i am just now going over. LOADED with SRMs for humans. NO wonder my neighbors mom died from CJD while taking these damn mad cow pills. THEY even have a candy bars loaded with SRMs.
HERE is one ;
NATURAL COCOA STANDARDBAR (mad cow candy bar) (i will just list animal organs) bovine adrenal, bovine liver, bovine spleen, ovine spleen, bovine kidney...
NATURAL PEANUT BUTTER STANDARDBAR bovine adrenal, bovine liver, bovine spleen, ovine spleen, bovine kidney...
USF (MAD COW) OINTMENT (RUB A DUB DUB, KURU ETC) ; bovine orhic glandular extract UTROPHIN PMG bovine uterus PMG VASCULIN bovine heart PMG extract, veal bone PMG extract, bovine liever, porcine duodenum, bovine adrenal Cytosol extract, bovine spleen, ovine spleen (some yummy stuff)
IPLEX (neighbors mom died from CJD while taking these pills for years) bovine eye PMG extract, veal bone PMG, bovine liver, porcine stomach, bovine adrenal, bovine kidney, bovine adrenal Cytosol extract, BOVINE BRAIN, bovine bone, veal bone meal MYO-PLUS bovine heart PMG, bovine liver, porcine stomach, bovine orchic extract, bovine spleen, ovine spleen, bovine adrenal Cytosol extract,
BOVINE BRAIN NEUROPLEX bovine orchic Cytosol extract, bovine spleen, BOVINE BRAIN PMG EXTRACT, BOVINE ANTERIOR PITUITARY, bovine liver, BOVINE PITUITARY PMG EXTRACT, AND MORE BOVINE BRAIN...
HOLY MAD COW IN A PILL !!! NEUROTROPHIN PMG BOVINE BRAIN PMG NIACINAMIDE B6 VM bovine liver, porcine stomach, bovine spleen ovine spleen, BOVINE BRAIN OCULOTROPHIN PMG BOVINE EYE PMG ORCHEX bovine liver, bovine orchic Cytosol extract, porcine stomch, bovine spleen, ovine spleen, BOVINE BRAIN OSTARPLEX veal bone PMG extract, veal bone PMG extract, bovine liver, porcine stomach, bovine adrenal, bovine spleen, ovine spleen, BOVINE BRAIN PARAPLEX bovine pancreas PMG extract, porcine duodenum, bovine adrenal PMG, BOVINE PITUITARY PMG EXTRACT, bovine thyroid PMG extract PITUITROPHIN PMG RUMAPLEX BOVINE BRAIN, veal bone PMG extract, bovine adrenal, bovine prostate Cytosol extract, veal bone meal, bovine liver PMG extract, bovine spleen, ovine spleen, bovine liver SENAPLEX bovine liver PMG extract, bovine adrenal, BOVNE BRAIN, veal bone meal, bovine kidney, bovine orchic extract, bovine spleen, ovine spleen ..........
THESE are just a few of MANY of just this ONE COMPANY.
Docket Management Docket: 96N-0417 - Current Good Manufacturing Practice in Manufacturing, Packing, or Holding Dietary Ingredients a Comment Number: EC -2 Accepted - Volume 7 253 1
DR. BOLTON: I have an additional question about 2 that. What is the assurance that additional locally sourced 3 tracheas are not added into that manufacturing process, thus 4 boosting the yield, if you will, but being returned to the 5 U.S. as being produced from U.S.-sourced raw material? 6 DR. McCURDY: Are there data to indicate how many 7 grams, or whatever, of infected brain are likely to infect 8 an organism, either animal or man, when taken orally? 9 DR. BROWN: If I am not mistaken, and I can be 10 corrected, I think a half a gram is enough in a cow, orally; 11 in other words, one good dietary-supplement pill. 12 DR. McCURDY: What I am driving at is the question 13 we are asked is really not do we wish to regulate these 14 things coming in. I think the statements about difficulties 15 in regulating things in the future or near future for new 16 regulations were probably accurate. 17 But I think that we could exhibit some quite 18 reasonable concern about blood donors who are taking dietary 19 supplements that contain a certain amount of unspecified- 20 origin brain, brain-related, brain and pituitary material. 21 If they have done this for more than a sniff or something 22 like that, then, perhaps, they should be deferred as blood 23 donors. 24 That is probably worse than spending six months in 25 the U.K. 254 1 DR. BROWN: That is exactly right. I think that 2 is why the discussion has apparently been on things that are 3 not directly related to these questions because, in order to 4 think about deferrals for blood donors who are taking 5 dietary supplements with things like bovine brain in them, 6 it is very important that we know that those products are 7 safe. 8 I think we have heard enough to suggest that they 9 may not be. 10 DR. McCURDY: There is one other item that needs 11 to be considered and that is what proportion of blood donors 12 are doing this; that is, how many blood donors would you 13 lose, and I don't know what the demographics--there is 14 fairly good information on the demography of blood donors. 15 I have no idea what the demography of people who take these 16 supplements is. Maybe they are old men like me and aren't 17 going to be blood donors anymore. 18 DR. BROWN: The wording of the question is not as 19 demanding as the wording of other deferral questions; that 20 is, the question here is consider recommending. We are 21 not even recommending at this point. We are saying to the 22 FDA, please think about this. It is worth thinking about. 23 DR. DETWILER: One point about brain from Europe, 24 and Jean Philippe is still here, those are considered 25 specified risk material and it is not correct to be 255 1 incinerated; correct? Or destroyed? Brain and spinal cord 2 and other high-risk tissues in Europe? 3 DR. NORTON: In tomorrow morning's British Medical 4 Journal, which has appeared on-line today, there is an 5 article called U.S. Takes Precautions against BSE. One 6 paragraph says, Even though the U.S. and U.K. governments 7 ban the practice of feeding cattle products to cows, in the 8 early 1990s, some U.K. renderers continued to manufacture 9 and ship contaminated meat and bonemeal around the world. 10 British export statistics show that thirty-seven tons of 11 meal made from offal was sent to the United States in 1997, 12 well after the U.S. government banned imports of such risky 13 meat. The ultimate use of these imports has not been 14 identified. 15 That will appear tomorrow morning. 16 DR. DETWILER: That actually was in The New York 17 Times. That is a direct quote out of The New York Times 18 article. We called the reporter on that. That statement, 19 the thirty-seven tons, was taken out of the U.S. 20 Geographical BSE Risk Assessment. What they didn't put in 21 there, in the statement, was the remainder of the GBR is at 22 that time, the big labeling for that category in the U.K., 23 because it was illegal for them to ship it to us from their 24 own regs. It is illegal for us to get that. 25 We did go and try and trace that so that wasn't
[FULL TEXT ABOUT 600 PAGES] 3681t2.rtf
http://www.fda.gov/ohrms/dockets/ac/cber01.htm
http://www.fda.gov/ohrms/dockets/dailys/03/Mar03/031403/96N-0417-EC-2.htm
IN fact, we are now finding that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of the cows to come down with BSE ; Published online January 27, 2005 Risk of oral infection with bovine spongiform encephalopathy agent in primates Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)—which can lead to variant Creutzfeldt-Jakob disease (vCJD)—is compounded by incomplete knowledge about the ef.ciency of oral infection and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the other remained free of disease at 76 months. On the basis of these .ndings and data from other studies, we made a preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public health measures can prevent transmission of BSE to man. snip...
BSE bovine brain inoculum 100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg Primate (oral route)* 1/2 (50%) Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%) RIII mice (icip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%) PrPres biochemical detection
The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the .rst positive animal (%). The accuracy of bioassays is generally judged to be about plus or minus 1 log. icip=intracerebral and intraperitoneal. Table 1: Comparison of transmission rates in primates and cattle infected orally with similar BSE brain inocula snip...end www.thelancet.com Published online January 27, 2005 THEN you must consider cross contamination at feed mills and such. this has been well proven in both the UK and the USA to date via r-to-r feed ban violations. IT was proven in the UK that they indeed put profits before human health; [PDF]
The BSE Inquiry / Statement No. 14 Issued 20 March 1998 THE ...
The BSE Inquiry / Statement No. 14. Issued 20 March 1998 ...
number of feed compounders and it became clear that cross contamination of feeds could occur. ...
http://www.bseinquiry.gov.uk/files/ws/s014.pdf
[PDF] The BSE Inquiry / Statement No 76F (Supplementary) Mr Alan ... But the mainbut the main problem was probably cross-contamination. ...
http://www.bseinquiry.gov.uk/files/ws/s076f.pdf
STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995
snip...
To minimise the risk of farmers' claims for compensation from feed compounders. To minimise the potential damage to compound feed markets through adverse publicity. To maximise freedom of action for feed compounders, notably by maintaining the availability of meat and bone meal as a raw material in animal feeds, and ensuring time is available to make any changes which may be required.
snip...
THE FUTURE 4..........
MAFF remains under pressure in Brussels and is not skilled at handling potentially explosive issues. 5. Tests _may_ show that ruminant feeds have been sold which contain illegal traces of ruminant protein. More likely, a few positive test results will turn up but proof that a particular feed mill knowingly supplied it to a particular farm will be difficult if not impossible. 6. The threat remains real and it will be some years before feed compounders are free of it. The longer we can avoid any direct linkage between feed milling _practices_ and actual BSE cases, the more likely it is that serious damage can be avoided. ...
SEE full text ;
http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf
snip...
From: TSS Subject: Inspector to file charges against USDA for them charging him with misconduct on telling the truth about SRM mad cow violations Date: September 7, 2005 at 1:37 pm PST
Consumer Health Inspector to file charges against USDA
By Steve Mitchell Sep 6, 2005, 22:46 GMT WASHINGTON, DC, United States (UPI) --
The federal meat inspector who was charged with misconduct by the U.S. Department of Agriculture after he claimed mad cow disease safeguards were being violated at slaughterhouses told United Press International he plans to file charges against the agency. Stan Painter, a USDA inspector and chair of the National Joint Council of Food Inspection Locals, the inspectors union, notified the agency`s management in a letter last December he was aware of instances where the riskiest parts of older cows were not being marked or removed from processing. Painter worried these risky parts -- known as specified risk materials, or SRMs -- could enter the food supply and infect people, causing a fatal brain illness called variant Creutzfeldt Jakob disease. Two cases of mad cow have been detected in U.S. herds, and some suspect there are more. The USDA put the SRM safeguards in place in 2004 to protect the public from mad cow disease -- also known as bovine spongiform encephalopathy or BSE -- if more cases are detected. The USDA did not respond to Painter`s concerns until he made his letter known to news outlets. On Dec. 28, 2004, the agency charged Painter with personal misconduct for not revealing the names of the inspectors who told him of the SRM violations. Officials also told him he was under a formal investigation, which was dropped last month after the release of internal documents revealing more than 1,000 violations of the USDA`s SRM regulations. Painter said he thinks the USDA was attempting 'to harass and intimidate him (and) to have a chilling effect' on other inspectors. 'I plan to file charges against the agency,' he told UPI, adding he has not yet decided if he will go through the legal system, through internal USDA procedures or another avenue. Asked about Painter`s intent to bring charges, agency spokesman Steven Cohen told UPI the documents -- called noncompliance reports, or NRs -- demonstrate 'that BSE safeguard regulations are being enforced and prohibited materials did not reach the public.' Mad cow disease remains a sensitive topic for the USDA because it can have significant economic ramifications. The U.S. beef industry lost billions of dollars because more than 60 nations closed their borders in 2003 to American beef after the report of the first detected case in U.S. herds. Japan, formerly the largest importer of American beef, still has not reopened its borders. For months, USDA officials denied Painter`s allegations in media reports, saying they had investigated and found no evidence to substantiate his claims. The NRs released last month under the Freedom of Information Act, however, showed 1,036 violations of SRM regulations in at least 35 states, Puerto Rico and the Virgin Islands, with some plants being cited repeatedly for infractions. The USDA delayed releasing the documents for eight months despite a federal law mandating a response within 30 days. Patty Lovera, of the watchdog group Public Citizen, which requested the USDA documents, said some of the violations cited in the NRs are egregious. In one, an employee at a plant in Michigan was not properly marking older cows to have their SRMs removed because he did not have a pencil. In another, an employee in a Missouri plant was loading cow heads onto his pickup truck to take home to feed to his dog. Lovera charged the USDA with attempting to silence Painter and failing to address problems with the SRM ban. 'Their behavior through this whole thing is appalling,' she told UPI. 'Stan brought them concerns about a policy and instead of investigating the policy, they investigated him.' Last December, after Painter made his letter known publicly, the USDA sent an officer to Painter`s house while he was on leave to question him about the allegations in his letter. Later, USDA officials interrogated Painter twice, asking him for the names of the inspectors who told him about the violations. Painter said he intentionally was kept ignorant of the inspectors` names because he feared the agency would retaliate against them. Painter also said USDA officials did ot need the inspectors` names because they could determine where the infractions were occurring by looking at their database of NRs. Sometime around June the U.S. Embassy in Japan posted a notice on its Web site stating USDA officials had found no evidence to substantiate Painter`s claims and had requested a criminal investigation into his actions. The notice was removed in July after UPI reported its existence. Although Cohen acknowledged more than 1,000 NRs were written by USDA inspectors, he minimized their significance, saying they 'amount to less than one-half of one percent of the total written for all reasons by (USDA) inspection program personnel.' Lovera said any infraction of mad cow safeguards should be of concern, because this disease always is fatal in humans and cooking does not destroy the pathogen. 'You have very little margin of error for something you don`t want to get because you can`t cook it away and you can`t disinfect it,' she said. Painter said his concern now is what the agency will do to fix what he sees as shortcomings in the SRM policy. 'It`s a failed policy,' he said. 'It doesn`t protect the consumer.' Cohen did not respond to whether the USDA planned to change the SRM regulations. The USDA`s Office of Inspector General has launched an investigation to determine whether the regulations are being implemented effectively, and results are due out soon.
E-mail: sciencemail@upi.com Copyright 2005 by United Press International
http://washingtontimes.com/upi/20050906-050340-6793r.htm
*** makes no difference, GW will change the SRM rules like he has the BSE GBR risk assessment to the terribly flawed BSE MRR policy, the legal trading of all strains of TSE, the 'gold card'. ...TSS
IN a time when FDA/USDA et al should be strengthening the TSE regulations, it seems corporate interest has won out again over sound science and consumer protection from an agent that is 100% fatal for the ones that go clinical. With the many different atypical TSEs showing up in different parts of the world, and with GWs BSE MRR policy (the legal policy of trading all strains of TSEs), the battle that has waged for the last 25 years to eradicate this agent from this planet will be set back decades, if not lost for good. ...TSS
snip...
http://www.fda.gov/ohrms/dockets/dailys/03/Mar03/031403/96N-0417-EC-2.htm
http://www.fas.usda.gov/info/fr/2004/071404BSEFDA1.htm
http://www.fda.gov/ohrms/DOCKETS/dockets/04n0081/04n-0081-ref0001-Tab-A-vol6.pdf
APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15, 2006
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle 9/13/2005
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 [Federal Register: January 9, 2007 (Volume 72, Number 5)] [Proposed Rules] [Page 1101-1129] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr09ja07-21]
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f8152
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 Date: January 9, 2007 at 9:08 am PST
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f3412
Sunday, March 16, 2008 MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html
SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE
http://downercattle.blogspot.com/
SRM MAD COW RECALL 406 THOUSAND POUNDS CATTLE HEADS WITH TONSILS KANSAS
http://cjdmadcowbaseoct2007.blogspot.com/2008/04/srm-mad-cow-recall-406-thousand-pounds.html
SPECIFIED RISK MATERIALS
http://madcowspontaneousnot.blogspot.com/2008/02/specified-risk-materials-srm.html
CJD USA
*Acquired in UK ** Acquired in Saudi Arabia *** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007. **** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26 from 2007). Notes: -- Cases are listed based on the year of death when available. If the year of death is not available, the year of sample receipt is used. -- Referrals: Cases with possible or probable prion disease from which brain tissue or blood in the case of familial disease were submitted. -- Inconclusive: Cases in which the samples were not sufficient to make a diagnosis. -- Non-vCJD type unknown are cases in which the tissue submitted was adequate to establish the presence but not the type; in all cases, vCJD could be excluded. -- Communicated by: Terry S. Singeltary Sr.
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.
He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
ALL animals for human/animal consumption must be tested for TSE.
ALL human TSEs must be made reportable Nationally and Internationally, OF ALL AGES. ...TSS
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
Wednesday, April 16, 2008
A Case of Creutzfeldt-Jakob Disease with Alien Limb Syndrome and Elevated Thyroid Autoantibodies
P03.135] CSF Findings in a Large United States Sporadic CJD Cohort
Michael Geschwind, Aissa Haman, Charles Torres-Chae, Benjamin J. Raudabaugh, Gillian Devereux, Bruce Miller, San Francisco, CA
OBJECTIVE: Determine the CSF profile and the diagnostic sensitivity and specificity of various CSF proteins in a US sCJD cohort (n=196). BACKGROUND: The diagnostic utility of various biomarkers for CJD is controversial. We examined the sensitivity and specificity for various CSF proteins in 800 potential prion cases referred to our center over the past five years. DESIGN/METHODS: Medical records were reviewed and/or patients were evaluated at our center. Data was stored in a secure clinical relational database that was queried for CSF findings, including cell count, protein, IgG index, oligoclonal bands (OCBs), 14-3-3, neuron specific enolase (NSE), Total Tau (T-Tau) in patients with probable or definite sporadic CJD and non-prion rapidly progressive dementias (RPD), most of whom were referred as suspected CJD cases. T-Tau positive if >1300 pg/ml; NSE positive if >35 ng/ml. Probable sCJD diagnosis was based on modifications to WHO 1998 criteria, allowing other focal cortical signs (e.g., aphasia, apraxia, neglect) AND a positive MRI or EEG (14-3-3 not used for diagnosis). RESULTS: 14-3-3 protein (n=131) sensitivity was only 50% (47% for definite; 52% for probable sCJD). NSE (n=34) sensitivity was 59% (65% for definite; 50% for probable sCJD). T-Tau (n=18) was the most sensitive at 72% (78% for definite; 67% for probable sCJD). The specificity of these biomarkers among our CJD and RPD controls (n=68) was 70% for 14-3-3 (n=33), 80% for NSE (n=15), and 100% for T-Tau (n=4). The 14-3-3 had the lowest sensitivity and specificity. CONCLUSIONS/RELEVANCE: Our data is contrary to other published data suggesting high sensitivity and specificity of these proteins for sCJD. DWI MRI has better sensitivity and specificity and should be used in diagnostic criteria. We question the utility of these CSF proteins for CJD diagnosis. A prion-specific test is needed. Supported by: John Douglas French Foundation for Alzheimers Research, the McBean Foundation, NIA K23AG021989-01, NIH-NINDS contract N01-NS-0-2328. Category - Aging and Dementia SubCategory - Clinical
Tuesday, May 1, 2007 4:00 PM
Poster Sessions: HIV and Prion Diseases (4:00 PM-7:30 PM)
The embargo for all abstracts to be presented at the 59th Annual Meeting is in effect until the date and time of the presentation unless otherwise noted on the abstract and/or press release. If there are questions, please contact the AAN media and public relations team.
===============================
http://www.abstracts2view.com/aan2007boston/sessionindex.php?day=2007-05-01&session=PO02-L
Debate Continues as New Studies Support MRI, Not CSF Markers, to Diagnose CJD
Neurology Today 5 June 2007; Volume 7(11); pp 6,10-11 Hurley, Dan
Outline article in brief study protocols experts comment mri as a diagnostic tool references Links View Article PDF
ARTICLE IN BRIEF
1. Two new studies aim to improve diagnosis of Creutzfeldt-Jakob Disease (CJD): one found a low sensitivity and specificity for CSF biomarkers for sporadic CJD; another study found MRI an effective diagnostic tool in a small number of patients with familial CJD.
BOSTON-A new, larger study by a San Francisco neurologist who previously challenged the use of the 14-3-3 protein in CSF for diagnosing sporadic Creutzfeldt-Jakob Disease (CJD) has again found a disappointingly low sensitivity and specificity for the biomarker.
Although the specificity and sensitivity of two other biomarkers, neuron specific enolase (NSE) and Total Tau (T-Tau), proved better than those of 14-3-3, neither were good enough to make them useful in diagnosing CJD, concluded Michael D. Geschwind, MD, PhD, assistant professor of neurology at the Memory and Aging Center of the University of California-San Francisco (UCSF). The findings were presented in a poster session here at the AAN annual meeting in May.
MRI appears to be a more reliable diagnostic tool, Dr. Geschwind said, and that view was supported by another poster at the meeting reporting high sensitivity and specificity for familial CJD with diffusion tensor imaging (DTI).
STUDY PROTOCOLS
Dr. Geschwind and colleagues examined the sensitivity and specificity for CSF in potential prion cases referred to the UCSF center in the past five years. Among 142 patients tested for 14-3-3, the sensitivity was only 49 percent overall - 47 percent for those with a diagnosis of sporadic CJD, and 50 percent for those with probable CJD.
Among the 40 tested for NSE, sensitivity was 63 percent (64 percent for definite CJD; 60 percent for probable CJD). Among the 20 tested for T-Tau, sensitivity was 70 percent (67 percent for definite CJD; 75 percent for probable CJD).
The specificity of the three biomarkers was 66 percent among the 44 controls tested for 14-3-3, 83 percent among the 18 controls tested for NSE, and 100 percent for the four controls tested for T-Tau.
Our data are contrary to other published results suggesting high sensitivity and specificity of these proteins for sporadic CJD, according to Dr. Geschwind and colleagues. We question the utility of these CSF proteins for CJD diagnosis.
EXPERTS COMMENT
But two neurologists who have led other studies with more positive findings said their views remain unchanged - that the biomarkers are a useful, though imperfect, tool for diagnosing CJD.
The data have limitations but also strengths, said Allen J. Aksamit Jr., MD, associate professor of neurology at the Mayo Clinic College of Medicine in Rochester, MN. If you have a select patient group who fit the clinical criteria for CJD and exclude every other possible diagnosis, it's a fairly sensitive and specific test. You use it as a weight to put on one side for or against the diagnosis.
In 2003, Dr. Aksamit espoused a similar view in an Archives of Neurology editorial (60:803-804) accompanying Dr. Geschwind's first paper challenging the clinical value of the 14-3-3 protein for diagnosis of sporadic CJD. In that study, Dr. Geschwind reviewed 32 pathologically confirmed cases on which 14-3-3 testing had been performed; only 17 cases had a positive result, a sensitivity of only 53 percent (Arch Neurol 2003;60:813-816).
Figure. Dr. Allen J. Aksamit Jr.: The data have limitations but also strengths. If you have a select patient group who fit the clinical criteria for CJD and exclude every other possible diagnosis, it's a fairly sensitive and specific test. You use it as a weight to put on one side for or against the diagnosis.
[ Click here to enlarge ] The largest data set published so far on biomarkers in CJD patients comes from a European consortium led by Inga Zerr, MD, a neurologist at Georg-August University in Götingen, Germany. She and colleagues reported last year on 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD and 1,179 controls, finding a sensitivity of 85 percent for 14-3-3, 86 percent for T-Tau, and 93 percent when the results of both tests were combined with S100b and NSE (Neurology 2006;67:637-643).
I am aware that the sensitivity of the tests in Dr. Geschwind's laboratory is lower than we reported and I have discussed this with him on several occasions, Dr. Zerr said in an e-mail. I have no idea why the data are so different.
One possible explanation, she and Dr. Aksamit suggested, is that at UCSF - a referral institution where many patients go for a second opinion - Dr. Geschwind is seeing more patients with slowly progressing disease than in the European group. Dr. Zerr's data showed, as have previous studies, that the sensitivity of the biomarkers is highest in patients with the shortest disease duration.
Another possible reason the two studies have reached such different conclusions is that Dr. Zerr included patients with genetic, iatrogenic, and variant CJD, whereas Dr. Geschwind's group includes only sporadic cases. Different case definitions and different testing methods might also contribute to the different findings.
Figure. Dr. Isak Prohovnik: MRI does seem to have better sensitivity and specificity than the biomarkers. But neither our group nor his [Dr. Geschwind's] have sufficient numbers yet.
[ Click here to enlarge ] In an interview with Neurology Today, Dr. Geschwind said of the European group's findings, I think they may have a selection bias. Every time they publish a study, their sensitivity goes lower and lower. Eventually it will hit ours.
He added in an e-mail, I believe there are occasional cases in which these biomarkers, such as the 14-3-3, total-tau or NSE, may be helpful in diagnosing CJD. The problem is that because these CSF proteins clearly can be elevated in other diseases that clinically mimic CJD, one must be very thorough in ruling out other conditions. Some of these conditions include cancers, neurologic autoimmune (paraneoplastic and non-paraneoplastic) dementias, sarcoid, Hashimoto encephalopathy, and even atypically rapid presentations of other neurodegenerative diseases.
After speaking with Dr. Geschwind in front of his poster, Dr. Aksamit Jr. told Neurology Today: It's all in the selection of the patient population being reviewed, and how high you set the bar for these laboratory tests. If you set the bar high, you'll get higher specificity but lower sensitivity. Our recommendation at Mayo is to set the bar high, to enhance specificity at the expense of sensitivity.
Dr. Aksamit noted, however, that 14-3-3 is no longer being tested at Mayo, because the reagents for a quantitative version of the test, which the institution had preferred over the standard Western blot, are no longer available. Instead, Mayo is testing NSE.
Despite the questions raised by Dr. Geschwind's paper, Dr. Zerr said: I completely agree with Dr. Aksamit that biomarkers in CSF are useful, when tested in the right populations. This is what we always stress when we are talking with physicians: Use CSF in the right differential diagnosis; that is, in dementia.
MRI AS A DIAGNOSTIC TOOL
The one point on which all three neurologists agreed is that MRI seems to be a powerful diagnostic tool. Although MRI is not part of the clinical criteria for CJD yet, said Dr. Zerr, we strongly recommend that neurologists have the MRI done and consider it as an additional test.
Another poster presented at the meeting shared the results of DTI testing on a small group of patients with familial CJD. Isak Prohovnik, PhD, professor of psychiatry and radiology at Mount Sinai School of Medicine in New York City, reported that DTI was abnormal in the basal ganglia of ten of 11 patients, eight of 11 in different cortical areas, and six of 11 in the thalami. No involvement was seen in the brain stem or cerebellum.
When correlated with the clinical findings, DTI was positive for the frontal cortex in eight of nine patients, and for the motor cortex in seven of nine patients. In the basal ganglia, the DTI was positive in 10 patients, although clinical findings were present in only eight. Clinical cerebellar signs were seen in 11 patients and brain-stem signs in seven of the 11, although no positive findings showed up in those regions on either DTI or other MRI sequences.
MRI does seem to have better sensitivity and specificity than the biomarkers, Dr. Prohovnik said, noting that Dr. Geschwind has also used MRI. But neither our group nor his have sufficient numbers yet.
In 2005, Dr. Geschwind co-authored a paper on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) in CJD, finding them to be 91 percent sensitive, 95 percent specific, and 94 percent accurate (Am J Neuroradiol 26:1551-1562). In 2005, Dr. Zerr was the senior author on a paper published in Brain (128:2026-2033), which concluded that FLAIR and DWI improved the clinical diagnosis and should be incorporated in the World Health Organization's diagnostic criteria for sporadic CJD.
REFERENCES
• Aksamit AJ. Cerebrospinal fluid 14-3-3 protein: Variability of sporadic Creutzfeldt-Jakob disease, laboratory standards, and quantitation.
• Geschwind MD, Martindale BS, Miller BL, et al. Challenging the clinical utility of the 14-3-3 protein for the diagnosis of sporadic Creutzfeldt-Jakob disease.
• Sanchez-Juan P, Green A, Zerr I, et al. CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease.
• Young GS, Geschwind MD, Dillon WP, et al. Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt-Jakob disease: High sensitivity for diagnosis.
• Tschampa HJ, Kellenberg K, Zerr I, et al. MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease: A study on inter-observer agreement.
http://www.aan.com/elibrary/neurologytoday/?event=home.showArticle&id=ovid.com%3a%2fbib%2fovftdb%2f00132985-200706050-00006
CJD USA
*Acquired in UK ** Acquired in Saudi Arabia *** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007. **** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26 from 2007).
Notes:
-- Cases are listed based on the year of death when available. If the year of death is not available, the year of sample receipt is used.
-- Referrals: Cases with possible or probable prion disease from which brain tissue or blood in the case of familial disease were submitted.
-- Inconclusive: Cases in which the samples were not sufficient to make a diagnosis.
-- Non-vCJD type unknown are cases in which the tissue submitted was adequate to establish the presence but not the type; in all cases, vCJD could be excluded.
-- Communicated by: Terry S. Singeltary Sr.
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.
He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
JOURNAL OF NEUROLOGY
MARCH 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
http://www.thepathologicalprotein.com/
doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003. Volume 3, Issue 8, August 2003, Page 463
"My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem." ...
http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext
http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734.
Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT
http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
http://www.bmj.com/cgi/eletters/320/7226/8/b#6117
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406
APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15, 2006
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle
9/13/2005
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
Sunday, March 16, 2008
MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html
SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE
http://downercattle.blogspot.com/
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
Friday, March 21, 2008
Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease
Original Paper
http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html
TSS
Michael Geschwind, Aissa Haman, Charles Torres-Chae, Benjamin J. Raudabaugh, Gillian Devereux, Bruce Miller, San Francisco, CA
OBJECTIVE: Determine the CSF profile and the diagnostic sensitivity and specificity of various CSF proteins in a US sCJD cohort (n=196). BACKGROUND: The diagnostic utility of various biomarkers for CJD is controversial. We examined the sensitivity and specificity for various CSF proteins in 800 potential prion cases referred to our center over the past five years. DESIGN/METHODS: Medical records were reviewed and/or patients were evaluated at our center. Data was stored in a secure clinical relational database that was queried for CSF findings, including cell count, protein, IgG index, oligoclonal bands (OCBs), 14-3-3, neuron specific enolase (NSE), Total Tau (T-Tau) in patients with probable or definite sporadic CJD and non-prion rapidly progressive dementias (RPD), most of whom were referred as suspected CJD cases. T-Tau positive if >1300 pg/ml; NSE positive if >35 ng/ml. Probable sCJD diagnosis was based on modifications to WHO 1998 criteria, allowing other focal cortical signs (e.g., aphasia, apraxia, neglect) AND a positive MRI or EEG (14-3-3 not used for diagnosis). RESULTS: 14-3-3 protein (n=131) sensitivity was only 50% (47% for definite; 52% for probable sCJD). NSE (n=34) sensitivity was 59% (65% for definite; 50% for probable sCJD). T-Tau (n=18) was the most sensitive at 72% (78% for definite; 67% for probable sCJD). The specificity of these biomarkers among our CJD and RPD controls (n=68) was 70% for 14-3-3 (n=33), 80% for NSE (n=15), and 100% for T-Tau (n=4). The 14-3-3 had the lowest sensitivity and specificity. CONCLUSIONS/RELEVANCE: Our data is contrary to other published data suggesting high sensitivity and specificity of these proteins for sCJD. DWI MRI has better sensitivity and specificity and should be used in diagnostic criteria. We question the utility of these CSF proteins for CJD diagnosis. A prion-specific test is needed. Supported by: John Douglas French Foundation for Alzheimers Research, the McBean Foundation, NIA K23AG021989-01, NIH-NINDS contract N01-NS-0-2328. Category - Aging and Dementia SubCategory - Clinical
Tuesday, May 1, 2007 4:00 PM
Poster Sessions: HIV and Prion Diseases (4:00 PM-7:30 PM)
The embargo for all abstracts to be presented at the 59th Annual Meeting is in effect until the date and time of the presentation unless otherwise noted on the abstract and/or press release. If there are questions, please contact the AAN media and public relations team.
===============================
http://www.abstracts2view.com/aan2007boston/sessionindex.php?day=2007-05-01&session=PO02-L
Debate Continues as New Studies Support MRI, Not CSF Markers, to Diagnose CJD
Neurology Today 5 June 2007; Volume 7(11); pp 6,10-11 Hurley, Dan
Outline article in brief study protocols experts comment mri as a diagnostic tool references Links View Article PDF
ARTICLE IN BRIEF
1. Two new studies aim to improve diagnosis of Creutzfeldt-Jakob Disease (CJD): one found a low sensitivity and specificity for CSF biomarkers for sporadic CJD; another study found MRI an effective diagnostic tool in a small number of patients with familial CJD.
BOSTON-A new, larger study by a San Francisco neurologist who previously challenged the use of the 14-3-3 protein in CSF for diagnosing sporadic Creutzfeldt-Jakob Disease (CJD) has again found a disappointingly low sensitivity and specificity for the biomarker.
Although the specificity and sensitivity of two other biomarkers, neuron specific enolase (NSE) and Total Tau (T-Tau), proved better than those of 14-3-3, neither were good enough to make them useful in diagnosing CJD, concluded Michael D. Geschwind, MD, PhD, assistant professor of neurology at the Memory and Aging Center of the University of California-San Francisco (UCSF). The findings were presented in a poster session here at the AAN annual meeting in May.
MRI appears to be a more reliable diagnostic tool, Dr. Geschwind said, and that view was supported by another poster at the meeting reporting high sensitivity and specificity for familial CJD with diffusion tensor imaging (DTI).
STUDY PROTOCOLS
Dr. Geschwind and colleagues examined the sensitivity and specificity for CSF in potential prion cases referred to the UCSF center in the past five years. Among 142 patients tested for 14-3-3, the sensitivity was only 49 percent overall - 47 percent for those with a diagnosis of sporadic CJD, and 50 percent for those with probable CJD.
Among the 40 tested for NSE, sensitivity was 63 percent (64 percent for definite CJD; 60 percent for probable CJD). Among the 20 tested for T-Tau, sensitivity was 70 percent (67 percent for definite CJD; 75 percent for probable CJD).
The specificity of the three biomarkers was 66 percent among the 44 controls tested for 14-3-3, 83 percent among the 18 controls tested for NSE, and 100 percent for the four controls tested for T-Tau.
Our data are contrary to other published results suggesting high sensitivity and specificity of these proteins for sporadic CJD, according to Dr. Geschwind and colleagues. We question the utility of these CSF proteins for CJD diagnosis.
EXPERTS COMMENT
But two neurologists who have led other studies with more positive findings said their views remain unchanged - that the biomarkers are a useful, though imperfect, tool for diagnosing CJD.
The data have limitations but also strengths, said Allen J. Aksamit Jr., MD, associate professor of neurology at the Mayo Clinic College of Medicine in Rochester, MN. If you have a select patient group who fit the clinical criteria for CJD and exclude every other possible diagnosis, it's a fairly sensitive and specific test. You use it as a weight to put on one side for or against the diagnosis.
In 2003, Dr. Aksamit espoused a similar view in an Archives of Neurology editorial (60:803-804) accompanying Dr. Geschwind's first paper challenging the clinical value of the 14-3-3 protein for diagnosis of sporadic CJD. In that study, Dr. Geschwind reviewed 32 pathologically confirmed cases on which 14-3-3 testing had been performed; only 17 cases had a positive result, a sensitivity of only 53 percent (Arch Neurol 2003;60:813-816).
Figure. Dr. Allen J. Aksamit Jr.: The data have limitations but also strengths. If you have a select patient group who fit the clinical criteria for CJD and exclude every other possible diagnosis, it's a fairly sensitive and specific test. You use it as a weight to put on one side for or against the diagnosis.
[ Click here to enlarge ] The largest data set published so far on biomarkers in CJD patients comes from a European consortium led by Inga Zerr, MD, a neurologist at Georg-August University in Götingen, Germany. She and colleagues reported last year on 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD and 1,179 controls, finding a sensitivity of 85 percent for 14-3-3, 86 percent for T-Tau, and 93 percent when the results of both tests were combined with S100b and NSE (Neurology 2006;67:637-643).
I am aware that the sensitivity of the tests in Dr. Geschwind's laboratory is lower than we reported and I have discussed this with him on several occasions, Dr. Zerr said in an e-mail. I have no idea why the data are so different.
One possible explanation, she and Dr. Aksamit suggested, is that at UCSF - a referral institution where many patients go for a second opinion - Dr. Geschwind is seeing more patients with slowly progressing disease than in the European group. Dr. Zerr's data showed, as have previous studies, that the sensitivity of the biomarkers is highest in patients with the shortest disease duration.
Another possible reason the two studies have reached such different conclusions is that Dr. Zerr included patients with genetic, iatrogenic, and variant CJD, whereas Dr. Geschwind's group includes only sporadic cases. Different case definitions and different testing methods might also contribute to the different findings.
Figure. Dr. Isak Prohovnik: MRI does seem to have better sensitivity and specificity than the biomarkers. But neither our group nor his [Dr. Geschwind's] have sufficient numbers yet.
[ Click here to enlarge ] In an interview with Neurology Today, Dr. Geschwind said of the European group's findings, I think they may have a selection bias. Every time they publish a study, their sensitivity goes lower and lower. Eventually it will hit ours.
He added in an e-mail, I believe there are occasional cases in which these biomarkers, such as the 14-3-3, total-tau or NSE, may be helpful in diagnosing CJD. The problem is that because these CSF proteins clearly can be elevated in other diseases that clinically mimic CJD, one must be very thorough in ruling out other conditions. Some of these conditions include cancers, neurologic autoimmune (paraneoplastic and non-paraneoplastic) dementias, sarcoid, Hashimoto encephalopathy, and even atypically rapid presentations of other neurodegenerative diseases.
After speaking with Dr. Geschwind in front of his poster, Dr. Aksamit Jr. told Neurology Today: It's all in the selection of the patient population being reviewed, and how high you set the bar for these laboratory tests. If you set the bar high, you'll get higher specificity but lower sensitivity. Our recommendation at Mayo is to set the bar high, to enhance specificity at the expense of sensitivity.
Dr. Aksamit noted, however, that 14-3-3 is no longer being tested at Mayo, because the reagents for a quantitative version of the test, which the institution had preferred over the standard Western blot, are no longer available. Instead, Mayo is testing NSE.
Despite the questions raised by Dr. Geschwind's paper, Dr. Zerr said: I completely agree with Dr. Aksamit that biomarkers in CSF are useful, when tested in the right populations. This is what we always stress when we are talking with physicians: Use CSF in the right differential diagnosis; that is, in dementia.
MRI AS A DIAGNOSTIC TOOL
The one point on which all three neurologists agreed is that MRI seems to be a powerful diagnostic tool. Although MRI is not part of the clinical criteria for CJD yet, said Dr. Zerr, we strongly recommend that neurologists have the MRI done and consider it as an additional test.
Another poster presented at the meeting shared the results of DTI testing on a small group of patients with familial CJD. Isak Prohovnik, PhD, professor of psychiatry and radiology at Mount Sinai School of Medicine in New York City, reported that DTI was abnormal in the basal ganglia of ten of 11 patients, eight of 11 in different cortical areas, and six of 11 in the thalami. No involvement was seen in the brain stem or cerebellum.
When correlated with the clinical findings, DTI was positive for the frontal cortex in eight of nine patients, and for the motor cortex in seven of nine patients. In the basal ganglia, the DTI was positive in 10 patients, although clinical findings were present in only eight. Clinical cerebellar signs were seen in 11 patients and brain-stem signs in seven of the 11, although no positive findings showed up in those regions on either DTI or other MRI sequences.
MRI does seem to have better sensitivity and specificity than the biomarkers, Dr. Prohovnik said, noting that Dr. Geschwind has also used MRI. But neither our group nor his have sufficient numbers yet.
In 2005, Dr. Geschwind co-authored a paper on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) in CJD, finding them to be 91 percent sensitive, 95 percent specific, and 94 percent accurate (Am J Neuroradiol 26:1551-1562). In 2005, Dr. Zerr was the senior author on a paper published in Brain (128:2026-2033), which concluded that FLAIR and DWI improved the clinical diagnosis and should be incorporated in the World Health Organization's diagnostic criteria for sporadic CJD.
REFERENCES
• Aksamit AJ. Cerebrospinal fluid 14-3-3 protein: Variability of sporadic Creutzfeldt-Jakob disease, laboratory standards, and quantitation.
• Geschwind MD, Martindale BS, Miller BL, et al. Challenging the clinical utility of the 14-3-3 protein for the diagnosis of sporadic Creutzfeldt-Jakob disease.
• Sanchez-Juan P, Green A, Zerr I, et al. CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease.
• Young GS, Geschwind MD, Dillon WP, et al. Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt-Jakob disease: High sensitivity for diagnosis.
• Tschampa HJ, Kellenberg K, Zerr I, et al. MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease: A study on inter-observer agreement.
http://www.aan.com/elibrary/neurologytoday/?event=home.showArticle&id=ovid.com%3a%2fbib%2fovftdb%2f00132985-200706050-00006
CJD USA
*Acquired in UK ** Acquired in Saudi Arabia *** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007. **** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26 from 2007).
Notes:
-- Cases are listed based on the year of death when available. If the year of death is not available, the year of sample receipt is used.
-- Referrals: Cases with possible or probable prion disease from which brain tissue or blood in the case of familial disease were submitted.
-- Inconclusive: Cases in which the samples were not sufficient to make a diagnosis.
-- Non-vCJD type unknown are cases in which the tissue submitted was adequate to establish the presence but not the type; in all cases, vCJD could be excluded.
-- Communicated by: Terry S. Singeltary Sr.
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.
He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
JOURNAL OF NEUROLOGY
MARCH 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
http://www.thepathologicalprotein.com/
doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003. Volume 3, Issue 8, August 2003, Page 463
"My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem." ...
http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext
http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734.
Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT
http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
http://www.bmj.com/cgi/eletters/320/7226/8/b#6117
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406
APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15, 2006
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle
9/13/2005
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
Sunday, March 16, 2008
MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html
SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE
http://downercattle.blogspot.com/
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
Friday, March 21, 2008
Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease
Original Paper
http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html
TSS
CSF Findings in a Large United States Sporadic CJD Cohort
P03.135] CSF Findings in a Large United States Sporadic CJD Cohort
Michael Geschwind, Aissa Haman, Charles Torres-Chae, Benjamin J. Raudabaugh, Gillian Devereux, Bruce Miller, San Francisco, CA
OBJECTIVE: Determine the CSF profile and the diagnostic sensitivity and specificity of various CSF proteins in a US sCJD cohort (n=196). BACKGROUND: The diagnostic utility of various biomarkers for CJD is controversial. We examined the sensitivity and specificity for various CSF proteins in 800 potential prion cases referred to our center over the past five years. DESIGN/METHODS: Medical records were reviewed and/or patients were evaluated at our center. Data was stored in a secure clinical relational database that was queried for CSF findings, including cell count, protein, IgG index, oligoclonal bands (OCBs), 14-3-3, neuron specific enolase (NSE), Total Tau (T-Tau) in patients with probable or definite sporadic CJD and non-prion rapidly progressive dementias (RPD), most of whom were referred as suspected CJD cases. T-Tau positive if >1300 pg/ml; NSE positive if >35 ng/ml. Probable sCJD diagnosis was based on modifications to WHO 1998 criteria, allowing other focal cortical signs (e.g., aphasia, apraxia, neglect) AND a positive MRI or EEG (14-3-3 not used for diagnosis). RESULTS: 14-3-3 protein (n=131) sensitivity was only 50% (47% for definite; 52% for probable sCJD). NSE (n=34) sensitivity was 59% (65% for definite; 50% for probable sCJD). T-Tau (n=18) was the most sensitive at 72% (78% for definite; 67% for probable sCJD). The specificity of these biomarkers among our CJD and RPD controls (n=68) was 70% for 14-3-3 (n=33), 80% for NSE (n=15), and 100% for T-Tau (n=4). The 14-3-3 had the lowest sensitivity and specificity. CONCLUSIONS/RELEVANCE: Our data is contrary to other published data suggesting high sensitivity and specificity of these proteins for sCJD. DWI MRI has better sensitivity and specificity and should be used in diagnostic criteria. We question the utility of these CSF proteins for CJD diagnosis. A prion-specific test is needed. Supported by: John Douglas French Foundation for Alzheimers Research, the McBean Foundation, NIA K23AG021989-01, NIH-NINDS contract N01-NS-0-2328. Category - Aging and Dementia SubCategory - Clinical
Tuesday, May 1, 2007 4:00 PM
Poster Sessions: HIV and Prion Diseases (4:00 PM-7:30 PM)
The embargo for all abstracts to be presented at the 59th Annual Meeting is in effect until the date and time of the presentation unless otherwise noted on the abstract and/or press release. If there are questions, please contact the AAN media and public relations team.
===============================
http://www.abstracts2view.com/aan2007boston/sessionindex.php?day=2007-05-01&session=PO02-L
Debate Continues as New Studies Support MRI, Not CSF Markers, to Diagnose CJD
Neurology Today 5 June 2007; Volume 7(11); pp 6,10-11 Hurley, Dan
Outline article in brief study protocols experts comment mri as a diagnostic tool references Links View Article PDF
ARTICLE IN BRIEF
1. Two new studies aim to improve diagnosis of Creutzfeldt-Jakob Disease (CJD): one found a low sensitivity and specificity for CSF biomarkers for sporadic CJD; another study found MRI an effective diagnostic tool in a small number of patients with familial CJD.
BOSTON-A new, larger study by a San Francisco neurologist who previously challenged the use of the 14-3-3 protein in CSF for diagnosing sporadic Creutzfeldt-Jakob Disease (CJD) has again found a disappointingly low sensitivity and specificity for the biomarker.
Although the specificity and sensitivity of two other biomarkers, neuron specific enolase (NSE) and Total Tau (T-Tau), proved better than those of 14-3-3, neither were good enough to make them useful in diagnosing CJD, concluded Michael D. Geschwind, MD, PhD, assistant professor of neurology at the Memory and Aging Center of the University of California-San Francisco (UCSF). The findings were presented in a poster session here at the AAN annual meeting in May.
MRI appears to be a more reliable diagnostic tool, Dr. Geschwind said, and that view was supported by another poster at the meeting reporting high sensitivity and specificity for familial CJD with diffusion tensor imaging (DTI).
STUDY PROTOCOLS
Dr. Geschwind and colleagues examined the sensitivity and specificity for CSF in potential prion cases referred to the UCSF center in the past five years. Among 142 patients tested for 14-3-3, the sensitivity was only 49 percent overall - 47 percent for those with a diagnosis of sporadic CJD, and 50 percent for those with probable CJD.
Among the 40 tested for NSE, sensitivity was 63 percent (64 percent for definite CJD; 60 percent for probable CJD). Among the 20 tested for T-Tau, sensitivity was 70 percent (67 percent for definite CJD; 75 percent for probable CJD).
The specificity of the three biomarkers was 66 percent among the 44 controls tested for 14-3-3, 83 percent among the 18 controls tested for NSE, and 100 percent for the four controls tested for T-Tau.
Our data are contrary to other published results suggesting high sensitivity and specificity of these proteins for sporadic CJD, according to Dr. Geschwind and colleagues. We question the utility of these CSF proteins for CJD diagnosis.
EXPERTS COMMENT
But two neurologists who have led other studies with more positive findings said their views remain unchanged - that the biomarkers are a useful, though imperfect, tool for diagnosing CJD.
The data have limitations but also strengths, said Allen J. Aksamit Jr., MD, associate professor of neurology at the Mayo Clinic College of Medicine in Rochester, MN. If you have a select patient group who fit the clinical criteria for CJD and exclude every other possible diagnosis, it's a fairly sensitive and specific test. You use it as a weight to put on one side for or against the diagnosis.
In 2003, Dr. Aksamit espoused a similar view in an Archives of Neurology editorial (60:803-804) accompanying Dr. Geschwind's first paper challenging the clinical value of the 14-3-3 protein for diagnosis of sporadic CJD. In that study, Dr. Geschwind reviewed 32 pathologically confirmed cases on which 14-3-3 testing had been performed; only 17 cases had a positive result, a sensitivity of only 53 percent (Arch Neurol 2003;60:813-816).
Figure. Dr. Allen J. Aksamit Jr.: The data have limitations but also strengths. If you have a select patient group who fit the clinical criteria for CJD and exclude every other possible diagnosis, it's a fairly sensitive and specific test. You use it as a weight to put on one side for or against the diagnosis.
[ Click here to enlarge ] The largest data set published so far on biomarkers in CJD patients comes from a European consortium led by Inga Zerr, MD, a neurologist at Georg-August University in Götingen, Germany. She and colleagues reported last year on 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD and 1,179 controls, finding a sensitivity of 85 percent for 14-3-3, 86 percent for T-Tau, and 93 percent when the results of both tests were combined with S100b and NSE (Neurology 2006;67:637-643).
I am aware that the sensitivity of the tests in Dr. Geschwind's laboratory is lower than we reported and I have discussed this with him on several occasions, Dr. Zerr said in an e-mail. I have no idea why the data are so different.
One possible explanation, she and Dr. Aksamit suggested, is that at UCSF - a referral institution where many patients go for a second opinion - Dr. Geschwind is seeing more patients with slowly progressing disease than in the European group. Dr. Zerr's data showed, as have previous studies, that the sensitivity of the biomarkers is highest in patients with the shortest disease duration.
Another possible reason the two studies have reached such different conclusions is that Dr. Zerr included patients with genetic, iatrogenic, and variant CJD, whereas Dr. Geschwind's group includes only sporadic cases. Different case definitions and different testing methods might also contribute to the different findings.
Figure. Dr. Isak Prohovnik: MRI does seem to have better sensitivity and specificity than the biomarkers. But neither our group nor his [Dr. Geschwind's] have sufficient numbers yet.
[ Click here to enlarge ] In an interview with Neurology Today, Dr. Geschwind said of the European group's findings, I think they may have a selection bias. Every time they publish a study, their sensitivity goes lower and lower. Eventually it will hit ours.
He added in an e-mail, I believe there are occasional cases in which these biomarkers, such as the 14-3-3, total-tau or NSE, may be helpful in diagnosing CJD. The problem is that because these CSF proteins clearly can be elevated in other diseases that clinically mimic CJD, one must be very thorough in ruling out other conditions. Some of these conditions include cancers, neurologic autoimmune (paraneoplastic and non-paraneoplastic) dementias, sarcoid, Hashimoto encephalopathy, and even atypically rapid presentations of other neurodegenerative diseases.
After speaking with Dr. Geschwind in front of his poster, Dr. Aksamit Jr. told Neurology Today: It's all in the selection of the patient population being reviewed, and how high you set the bar for these laboratory tests. If you set the bar high, you'll get higher specificity but lower sensitivity. Our recommendation at Mayo is to set the bar high, to enhance specificity at the expense of sensitivity.
Dr. Aksamit noted, however, that 14-3-3 is no longer being tested at Mayo, because the reagents for a quantitative version of the test, which the institution had preferred over the standard Western blot, are no longer available. Instead, Mayo is testing NSE.
Despite the questions raised by Dr. Geschwind's paper, Dr. Zerr said: I completely agree with Dr. Aksamit that biomarkers in CSF are useful, when tested in the right populations. This is what we always stress when we are talking with physicians: Use CSF in the right differential diagnosis; that is, in dementia.
MRI AS A DIAGNOSTIC TOOL
The one point on which all three neurologists agreed is that MRI seems to be a powerful diagnostic tool. Although MRI is not part of the clinical criteria for CJD yet, said Dr. Zerr, we strongly recommend that neurologists have the MRI done and consider it as an additional test.
Another poster presented at the meeting shared the results of DTI testing on a small group of patients with familial CJD. Isak Prohovnik, PhD, professor of psychiatry and radiology at Mount Sinai School of Medicine in New York City, reported that DTI was abnormal in the basal ganglia of ten of 11 patients, eight of 11 in different cortical areas, and six of 11 in the thalami. No involvement was seen in the brain stem or cerebellum.
When correlated with the clinical findings, DTI was positive for the frontal cortex in eight of nine patients, and for the motor cortex in seven of nine patients. In the basal ganglia, the DTI was positive in 10 patients, although clinical findings were present in only eight. Clinical cerebellar signs were seen in 11 patients and brain-stem signs in seven of the 11, although no positive findings showed up in those regions on either DTI or other MRI sequences.
MRI does seem to have better sensitivity and specificity than the biomarkers, Dr. Prohovnik said, noting that Dr. Geschwind has also used MRI. But neither our group nor his have sufficient numbers yet.
In 2005, Dr. Geschwind co-authored a paper on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) in CJD, finding them to be 91 percent sensitive, 95 percent specific, and 94 percent accurate (Am J Neuroradiol 26:1551-1562). In 2005, Dr. Zerr was the senior author on a paper published in Brain (128:2026-2033), which concluded that FLAIR and DWI improved the clinical diagnosis and should be incorporated in the World Health Organization's diagnostic criteria for sporadic CJD.
REFERENCES
• Aksamit AJ. Cerebrospinal fluid 14-3-3 protein: Variability of sporadic Creutzfeldt-Jakob disease, laboratory standards, and quantitation.
• Geschwind MD, Martindale BS, Miller BL, et al. Challenging the clinical utility of the 14-3-3 protein for the diagnosis of sporadic Creutzfeldt-Jakob disease.
• Sanchez-Juan P, Green A, Zerr I, et al. CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease.
• Young GS, Geschwind MD, Dillon WP, et al. Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt-Jakob disease: High sensitivity for diagnosis.
• Tschampa HJ, Kellenberg K, Zerr I, et al. MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease: A study on inter-observer agreement.
http://www.aan.com/elibrary/neurologytoday/?event=home.showArticle&id=ovid.com%3a%2fbib%2fovftdb%2f00132985-200706050-00006
CJD USA
*Acquired in UK ** Acquired in Saudi Arabia *** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007. **** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26 from 2007).
Notes:
-- Cases are listed based on the year of death when available. If the year of death is not available, the year of sample receipt is used.
-- Referrals: Cases with possible or probable prion disease from which brain tissue or blood in the case of familial disease were submitted.
-- Inconclusive: Cases in which the samples were not sufficient to make a diagnosis.
-- Non-vCJD type unknown are cases in which the tissue submitted was adequate to establish the presence but not the type; in all cases, vCJD could be excluded.
-- Communicated by: Terry S. Singeltary Sr.
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.
He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
JOURNAL OF NEUROLOGY
MARCH 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to
comment on the CDC's attempts to monitor the occurrence of emerging
forms of CJD. Asante, Collinge et al [1] have reported that BSE
transmission to the 129-methionine genotype can lead to an alternate
phenotype that is indistinguishable from type 2 PrPSc, the commonest
sporadic CJD. However, CJD and all human TSEs are not reportable
nationally. CJD and all human TSEs must be made reportable in every
state and internationally. I hope that the CDC does not continue to
expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in
the USA in both animal and man. CWD in deer/elk is spreading rapidly and
CWD does transmit to mink, ferret, cattle, and squirrel monkey by
intracerebral inoculation. With the known incubation periods in other
TSEs, oral transmission studies of CWD may take much longer. Every
victim/family of CJD/TSEs should be asked about route and source of this
agent. To prolong this will only spread the agent and needlessly expose
others. In light of the findings of Asante and Collinge et al, there
should be drastic measures to safeguard the medical and surgical arena
from sporadic CJDs and all human TSEs. I only ponder how many sporadic
CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
http://www.thepathologicalprotein.com/
doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003. Volume 3, Issue 8, August 2003, Page 463
"My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem." ...
http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext
http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734.
Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT
http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
http://www.bmj.com/cgi/eletters/320/7226/8/b#6117
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406
APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15, 2006
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle
9/13/2005
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
Sunday, March 16, 2008
MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html
SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE
http://downercattle.blogspot.com/
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
Friday, March 21, 2008
Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease
Original Paper
http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html
TSS
Michael Geschwind, Aissa Haman, Charles Torres-Chae, Benjamin J. Raudabaugh, Gillian Devereux, Bruce Miller, San Francisco, CA
OBJECTIVE: Determine the CSF profile and the diagnostic sensitivity and specificity of various CSF proteins in a US sCJD cohort (n=196). BACKGROUND: The diagnostic utility of various biomarkers for CJD is controversial. We examined the sensitivity and specificity for various CSF proteins in 800 potential prion cases referred to our center over the past five years. DESIGN/METHODS: Medical records were reviewed and/or patients were evaluated at our center. Data was stored in a secure clinical relational database that was queried for CSF findings, including cell count, protein, IgG index, oligoclonal bands (OCBs), 14-3-3, neuron specific enolase (NSE), Total Tau (T-Tau) in patients with probable or definite sporadic CJD and non-prion rapidly progressive dementias (RPD), most of whom were referred as suspected CJD cases. T-Tau positive if >1300 pg/ml; NSE positive if >35 ng/ml. Probable sCJD diagnosis was based on modifications to WHO 1998 criteria, allowing other focal cortical signs (e.g., aphasia, apraxia, neglect) AND a positive MRI or EEG (14-3-3 not used for diagnosis). RESULTS: 14-3-3 protein (n=131) sensitivity was only 50% (47% for definite; 52% for probable sCJD). NSE (n=34) sensitivity was 59% (65% for definite; 50% for probable sCJD). T-Tau (n=18) was the most sensitive at 72% (78% for definite; 67% for probable sCJD). The specificity of these biomarkers among our CJD and RPD controls (n=68) was 70% for 14-3-3 (n=33), 80% for NSE (n=15), and 100% for T-Tau (n=4). The 14-3-3 had the lowest sensitivity and specificity. CONCLUSIONS/RELEVANCE: Our data is contrary to other published data suggesting high sensitivity and specificity of these proteins for sCJD. DWI MRI has better sensitivity and specificity and should be used in diagnostic criteria. We question the utility of these CSF proteins for CJD diagnosis. A prion-specific test is needed. Supported by: John Douglas French Foundation for Alzheimers Research, the McBean Foundation, NIA K23AG021989-01, NIH-NINDS contract N01-NS-0-2328. Category - Aging and Dementia SubCategory - Clinical
Tuesday, May 1, 2007 4:00 PM
Poster Sessions: HIV and Prion Diseases (4:00 PM-7:30 PM)
The embargo for all abstracts to be presented at the 59th Annual Meeting is in effect until the date and time of the presentation unless otherwise noted on the abstract and/or press release. If there are questions, please contact the AAN media and public relations team.
===============================
http://www.abstracts2view.com/aan2007boston/sessionindex.php?day=2007-05-01&session=PO02-L
Debate Continues as New Studies Support MRI, Not CSF Markers, to Diagnose CJD
Neurology Today 5 June 2007; Volume 7(11); pp 6,10-11 Hurley, Dan
Outline article in brief study protocols experts comment mri as a diagnostic tool references Links View Article PDF
ARTICLE IN BRIEF
1. Two new studies aim to improve diagnosis of Creutzfeldt-Jakob Disease (CJD): one found a low sensitivity and specificity for CSF biomarkers for sporadic CJD; another study found MRI an effective diagnostic tool in a small number of patients with familial CJD.
BOSTON-A new, larger study by a San Francisco neurologist who previously challenged the use of the 14-3-3 protein in CSF for diagnosing sporadic Creutzfeldt-Jakob Disease (CJD) has again found a disappointingly low sensitivity and specificity for the biomarker.
Although the specificity and sensitivity of two other biomarkers, neuron specific enolase (NSE) and Total Tau (T-Tau), proved better than those of 14-3-3, neither were good enough to make them useful in diagnosing CJD, concluded Michael D. Geschwind, MD, PhD, assistant professor of neurology at the Memory and Aging Center of the University of California-San Francisco (UCSF). The findings were presented in a poster session here at the AAN annual meeting in May.
MRI appears to be a more reliable diagnostic tool, Dr. Geschwind said, and that view was supported by another poster at the meeting reporting high sensitivity and specificity for familial CJD with diffusion tensor imaging (DTI).
STUDY PROTOCOLS
Dr. Geschwind and colleagues examined the sensitivity and specificity for CSF in potential prion cases referred to the UCSF center in the past five years. Among 142 patients tested for 14-3-3, the sensitivity was only 49 percent overall - 47 percent for those with a diagnosis of sporadic CJD, and 50 percent for those with probable CJD.
Among the 40 tested for NSE, sensitivity was 63 percent (64 percent for definite CJD; 60 percent for probable CJD). Among the 20 tested for T-Tau, sensitivity was 70 percent (67 percent for definite CJD; 75 percent for probable CJD).
The specificity of the three biomarkers was 66 percent among the 44 controls tested for 14-3-3, 83 percent among the 18 controls tested for NSE, and 100 percent for the four controls tested for T-Tau.
Our data are contrary to other published results suggesting high sensitivity and specificity of these proteins for sporadic CJD, according to Dr. Geschwind and colleagues. We question the utility of these CSF proteins for CJD diagnosis.
EXPERTS COMMENT
But two neurologists who have led other studies with more positive findings said their views remain unchanged - that the biomarkers are a useful, though imperfect, tool for diagnosing CJD.
The data have limitations but also strengths, said Allen J. Aksamit Jr., MD, associate professor of neurology at the Mayo Clinic College of Medicine in Rochester, MN. If you have a select patient group who fit the clinical criteria for CJD and exclude every other possible diagnosis, it's a fairly sensitive and specific test. You use it as a weight to put on one side for or against the diagnosis.
In 2003, Dr. Aksamit espoused a similar view in an Archives of Neurology editorial (60:803-804) accompanying Dr. Geschwind's first paper challenging the clinical value of the 14-3-3 protein for diagnosis of sporadic CJD. In that study, Dr. Geschwind reviewed 32 pathologically confirmed cases on which 14-3-3 testing had been performed; only 17 cases had a positive result, a sensitivity of only 53 percent (Arch Neurol 2003;60:813-816).
Figure. Dr. Allen J. Aksamit Jr.: The data have limitations but also strengths. If you have a select patient group who fit the clinical criteria for CJD and exclude every other possible diagnosis, it's a fairly sensitive and specific test. You use it as a weight to put on one side for or against the diagnosis.
[ Click here to enlarge ] The largest data set published so far on biomarkers in CJD patients comes from a European consortium led by Inga Zerr, MD, a neurologist at Georg-August University in Götingen, Germany. She and colleagues reported last year on 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD and 1,179 controls, finding a sensitivity of 85 percent for 14-3-3, 86 percent for T-Tau, and 93 percent when the results of both tests were combined with S100b and NSE (Neurology 2006;67:637-643).
I am aware that the sensitivity of the tests in Dr. Geschwind's laboratory is lower than we reported and I have discussed this with him on several occasions, Dr. Zerr said in an e-mail. I have no idea why the data are so different.
One possible explanation, she and Dr. Aksamit suggested, is that at UCSF - a referral institution where many patients go for a second opinion - Dr. Geschwind is seeing more patients with slowly progressing disease than in the European group. Dr. Zerr's data showed, as have previous studies, that the sensitivity of the biomarkers is highest in patients with the shortest disease duration.
Another possible reason the two studies have reached such different conclusions is that Dr. Zerr included patients with genetic, iatrogenic, and variant CJD, whereas Dr. Geschwind's group includes only sporadic cases. Different case definitions and different testing methods might also contribute to the different findings.
Figure. Dr. Isak Prohovnik: MRI does seem to have better sensitivity and specificity than the biomarkers. But neither our group nor his [Dr. Geschwind's] have sufficient numbers yet.
[ Click here to enlarge ] In an interview with Neurology Today, Dr. Geschwind said of the European group's findings, I think they may have a selection bias. Every time they publish a study, their sensitivity goes lower and lower. Eventually it will hit ours.
He added in an e-mail, I believe there are occasional cases in which these biomarkers, such as the 14-3-3, total-tau or NSE, may be helpful in diagnosing CJD. The problem is that because these CSF proteins clearly can be elevated in other diseases that clinically mimic CJD, one must be very thorough in ruling out other conditions. Some of these conditions include cancers, neurologic autoimmune (paraneoplastic and non-paraneoplastic) dementias, sarcoid, Hashimoto encephalopathy, and even atypically rapid presentations of other neurodegenerative diseases.
After speaking with Dr. Geschwind in front of his poster, Dr. Aksamit Jr. told Neurology Today: It's all in the selection of the patient population being reviewed, and how high you set the bar for these laboratory tests. If you set the bar high, you'll get higher specificity but lower sensitivity. Our recommendation at Mayo is to set the bar high, to enhance specificity at the expense of sensitivity.
Dr. Aksamit noted, however, that 14-3-3 is no longer being tested at Mayo, because the reagents for a quantitative version of the test, which the institution had preferred over the standard Western blot, are no longer available. Instead, Mayo is testing NSE.
Despite the questions raised by Dr. Geschwind's paper, Dr. Zerr said: I completely agree with Dr. Aksamit that biomarkers in CSF are useful, when tested in the right populations. This is what we always stress when we are talking with physicians: Use CSF in the right differential diagnosis; that is, in dementia.
MRI AS A DIAGNOSTIC TOOL
The one point on which all three neurologists agreed is that MRI seems to be a powerful diagnostic tool. Although MRI is not part of the clinical criteria for CJD yet, said Dr. Zerr, we strongly recommend that neurologists have the MRI done and consider it as an additional test.
Another poster presented at the meeting shared the results of DTI testing on a small group of patients with familial CJD. Isak Prohovnik, PhD, professor of psychiatry and radiology at Mount Sinai School of Medicine in New York City, reported that DTI was abnormal in the basal ganglia of ten of 11 patients, eight of 11 in different cortical areas, and six of 11 in the thalami. No involvement was seen in the brain stem or cerebellum.
When correlated with the clinical findings, DTI was positive for the frontal cortex in eight of nine patients, and for the motor cortex in seven of nine patients. In the basal ganglia, the DTI was positive in 10 patients, although clinical findings were present in only eight. Clinical cerebellar signs were seen in 11 patients and brain-stem signs in seven of the 11, although no positive findings showed up in those regions on either DTI or other MRI sequences.
MRI does seem to have better sensitivity and specificity than the biomarkers, Dr. Prohovnik said, noting that Dr. Geschwind has also used MRI. But neither our group nor his have sufficient numbers yet.
In 2005, Dr. Geschwind co-authored a paper on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) in CJD, finding them to be 91 percent sensitive, 95 percent specific, and 94 percent accurate (Am J Neuroradiol 26:1551-1562). In 2005, Dr. Zerr was the senior author on a paper published in Brain (128:2026-2033), which concluded that FLAIR and DWI improved the clinical diagnosis and should be incorporated in the World Health Organization's diagnostic criteria for sporadic CJD.
REFERENCES
• Aksamit AJ. Cerebrospinal fluid 14-3-3 protein: Variability of sporadic Creutzfeldt-Jakob disease, laboratory standards, and quantitation.
• Geschwind MD, Martindale BS, Miller BL, et al. Challenging the clinical utility of the 14-3-3 protein for the diagnosis of sporadic Creutzfeldt-Jakob disease.
• Sanchez-Juan P, Green A, Zerr I, et al. CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease.
• Young GS, Geschwind MD, Dillon WP, et al. Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt-Jakob disease: High sensitivity for diagnosis.
• Tschampa HJ, Kellenberg K, Zerr I, et al. MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease: A study on inter-observer agreement.
http://www.aan.com/elibrary/neurologytoday/?event=home.showArticle&id=ovid.com%3a%2fbib%2fovftdb%2f00132985-200706050-00006
CJD USA
*Acquired in UK ** Acquired in Saudi Arabia *** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007. **** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26 from 2007).
Notes:
-- Cases are listed based on the year of death when available. If the year of death is not available, the year of sample receipt is used.
-- Referrals: Cases with possible or probable prion disease from which brain tissue or blood in the case of familial disease were submitted.
-- Inconclusive: Cases in which the samples were not sufficient to make a diagnosis.
-- Non-vCJD type unknown are cases in which the tissue submitted was adequate to establish the presence but not the type; in all cases, vCJD could be excluded.
-- Communicated by: Terry S. Singeltary Sr.
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.
He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
JOURNAL OF NEUROLOGY
MARCH 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to
comment on the CDC's attempts to monitor the occurrence of emerging
forms of CJD. Asante, Collinge et al [1] have reported that BSE
transmission to the 129-methionine genotype can lead to an alternate
phenotype that is indistinguishable from type 2 PrPSc, the commonest
sporadic CJD. However, CJD and all human TSEs are not reportable
nationally. CJD and all human TSEs must be made reportable in every
state and internationally. I hope that the CDC does not continue to
expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in
the USA in both animal and man. CWD in deer/elk is spreading rapidly and
CWD does transmit to mink, ferret, cattle, and squirrel monkey by
intracerebral inoculation. With the known incubation periods in other
TSEs, oral transmission studies of CWD may take much longer. Every
victim/family of CJD/TSEs should be asked about route and source of this
agent. To prolong this will only spread the agent and needlessly expose
others. In light of the findings of Asante and Collinge et al, there
should be drastic measures to safeguard the medical and surgical arena
from sporadic CJDs and all human TSEs. I only ponder how many sporadic
CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
http://www.thepathologicalprotein.com/
doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003. Volume 3, Issue 8, August 2003, Page 463
"My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem." ...
http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext
http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734.
Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT
http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
http://www.bmj.com/cgi/eletters/320/7226/8/b#6117
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406
APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15, 2006
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle
9/13/2005
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
Sunday, March 16, 2008
MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html
SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE
http://downercattle.blogspot.com/
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
Friday, March 21, 2008
Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease
Original Paper
http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html
TSS
Subscribe to:
Posts (Atom)
