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From: TSS ()
Subject: ABNORMAL PRION ACCUMULATION ASSOCIATED WITH RETINAL PATHOLOGY IN EXPERIMENTALLY INOCULATED SCRAPIE-AFFECTED SHEEP
Date: December 27, 2006 at 10:05 am PST

Title: ABNORMAL PRION ACCUMULATION ASSOCIATED WITH RETINAL PATHOLOGY IN EXPERIMENTALLY INOCULATED SCRAPIE-AFFECTED SHEEP


Authors

Greenlee, Justin
Hamir, Amirali
West Greenlee, M. Heather - IOWA STATE UNIVERSITY


Submitted to: Veterinary Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 25, 2006
Publication Date: September 1, 2006
Citation: Greenlee, J.J., Hamir, A.N., West Greenlee, M.H. 2006. Abnormal prion accumulation associated with retinal pathology in experimentally inoculated scrapie-affected sheep. Veterinary Pathology. 43:733-739.

Interpretive Summary: Scrapie is a naturally occurring fatal disease of sheep and goats affecting the nervous system. After infection, the scrapie agent is known to accumulate in the brain, lymph nodes, and retina, the specialized sensory structure lining the inside of the eye. All current methods of diagnosis for scrapie and related diseases require collection of brain tissue after death of the animal. This study uses special staining techniques to show that accumulation of the agent causing scrapie in sheep is associated with pathology in the retina. When small amounts of the agent causing scrapie were present in multiple, small areas of the retina, there was moderate positive staining to indicate cell injury. In eyes (retinae) with large amounts of agent present, staining to indicate damage to retinal cells was very abundant and spread throughout the entire retina. The inoculated animals were not examined for vision deficits, but the extent of special staining of damaged cells suggests that there may be functional deficits that could be measured possibly leading to new methods of disease diagnosis in live animals. Results of this study will have a possible impact on directing future research on live animal diagnostic methods for transmissible spongiform encephalopathies.
Technical Abstract: The purpose of this study was to characterize the patterns of PrP**Sc immunoreactivity in the retinae of scrapie-infected sheep and determine the extent of retinal pathology as indicated by Glial Fibrillary Acidic Protein immunoreactivity (GFAP-IR) of Müller glia. GFAP-IR of Müller glia is suggestive of retinal pathology in absence of morphologic abnormality detected by light microscopy. Sheep with the least amount of prion immunoreactivity have multifocal punctate aggregates of prion staining in the outer half of the inner plexiform layer and rarely in the outer plexiform layer. In these retinae, GFAP-IR is not localized with prion accumulation, but rather is present in moderate numbers of Müller glia throughout the sections of retina examined. The majority of affected retinae have intense, diffuse PrP**Sc staining in both plexiform layers with immunoreactivity in the cytoplasm of multifocal ganglion cells and lesser amounts in the optic fiber layer and between nuclei in nuclear layers. This intense PrP**Sc immunoreactivity is associated with diffuse, intense GFAP-IR from the inner limiting membrane to outer limiting membrane. This is the first report of prion disease in a natural host to describe the accumulation of PrP**Sc in retina associated with retinal pathology without overt morphologic changes indicative of retinal degeneration.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=180675

Vet Pathol 43:733-739 (2006)
© 2006 American College of Veterinary Pathologists

Abnormal Prion Accumulation Associated with Retinal Pathology in Experimentally Inoculated Scrapie-Affected Sheep
J. J. Greenlee, A. N. Hamir and M. H. West Greenlee
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA (JJG, ANH), and the Department of Biomedical Sciences, Interdepartmental Neuroscience Program, Bioinformatics and Computational Biology Program, Iowa State University, Ames, IA (MHWG)

The purpose of this study was to characterize the patterns of PrPSc immunoreactivity in the retinae of scrapie-affected sheep and to determine the extent of retinal pathology as indicated by glial fibrillary acidic protein immunoreactivity (GFAP-IR) of Müller glia. Sections from the retina of 13 experimentally inoculated scrapie-affected and 2 negative control sheep were examined with immunohistochemical staining for PrPSc, GFAP, and PrPSc/GFAP double staining. GFAP-IR of Müller glia is suggestive of retinal pathology in the absence of morphologic abnormality detected by light microscopy. Sheep with the least amount of PrPSc in the retina have multifocal punctate aggregates of prion staining in the outer half of the inner plexiform layer and rarely in the outer plexiform layer. In these retinae, GFAP-IR is not localized with prion accumulation, but rather is present in moderate numbers of Müller glia throughout the sections of retina examined. The majority of sheep with retinal accumulation of PrPSc have intense, diffuse PrPSc staining in both plexiform layers, with immunoreactivity in the cytoplasm of multiple ganglion cells and lesser amounts in the optic fiber layer and between nuclei in nuclear layers. This intense PrPSc immunoreactivity is associated with diffuse, intense GFAP-IR that extends from the inner limiting membrane to the outer limiting membrane. This is the first report of a prion disease in a natural host that describes the accumulation of PrPSc in retina associated with retinal pathology in the absence of overt morphologic changes indicative of retinal degeneration.

--------------------------------------------------------------------------------

Key words: Glial fibrillary acidic protein; immunohistochemistry; prion diseases; retina; scrapie; sheep; spongiform encephalopathy.

Request reprints from Dr. J J Greenlee, National Animal Disease Center, 2300 Dayton Ave., Ames, IA 50010

http://www.vetpathology.org/cgi/content/abstract/43/5/733

Subject: CJD SURGICAL INCIDENT REPORTING FORM UPDATE NOVEMBER 2006
Date: November 18, 2006 at 9:05 am PST
CJD SURGICAL INCIDENT REPORTING FORM UPDATE NOVEMBER 2006

snip...


7. Which tissues were involved?

Please tick Please circle or underline where appropriate
Any notes/details?


Brain

CNS / Spinal cord


Posterior eye / anterior eye / cornea


Olfactory epithelium


Tonsil / appendix / spleen / thymus


Other lymphoid tissue


Peripheral nerve


Dental pulp / gingival tissue / Blood / bone marrow / CSF / Placenta / Urine


Other or not know (please give available details):

8. How many instruments were used, and what were they?

(Please continue overleaf or attach details if necessary)


9. What type of decontamination procedures are used for these instruments?


10. How many times have the instruments been used and decontaminated since this procedure?


10. Can you trace the instruments?

(e.g. all / some / none / disposable / don?t know)


11. Where are the instruments now?*

(e.g. all are quarantined / some are quarantined / none are quarantined / not applicable/ don?t know)


12. How many people might have been exposed to the instruments (or pool of instruments)?


13. Other comments (Please continue overleaf or attach if necessary)


snip.....

http://www.hpa.org.uk/infections/topics_az/cjd/SI_formNov06.doc

http://brain.hastypastry.net/forums/showthread.php?t=4807

USA CJD QUESTIONNAIRE

http://brain.hastypastry.net/forums/showthread.php?referrerid=38487&t=2408

4 May 2004

Creutzfeldt-Jakob Disease (CJD) and Ophthalmology*

snip...

Patients with classical (sporadic) CJD are predominantly in their 60s and as such may come into contact with ophthalmologists because of cataract, glaucoma and macular degeneration, or because of visual symptoms caused by their condition5. Although there is no clear evidence of the transmission of spongiform encephalopathy from one patient to another by ophthalmic surgery other than through corneal transplantation6, it has been accepted for many years that instruments used on patients with known or suspected CJD undergoing any surgical procedure, should be destroyed7.

snip...

5. Action if exposure to risk of CJD occurs

The CJD Incidents Panel (established November 2000) is aware of over 140 separate incidents in which patients may have been put at risk because of instruments or devices previously used on patients who had or have gone on to develop either form of CJD. There have been 13 ophthalmological incidents mostly involving patients destined to develop sporadic CJD who have had cataract surgery.

If a patient undergoing ophthalmic surgery subsequently develops any form of CJD, it is essential that all instruments and devices involved should be traceable and taken out of circulation, and that subsequent patients who may have inadvertently been put at risk can be identified. For further advice in such an event contact Dr Nicky Connor, CJD Panel Secretariat, HPA, CDSC, 61 Colindale Avenue, London NW9 5EQ, tel: 0208 200 6868 ext.3411, e-mail: nicky.connor@hpa.org.uk

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

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

CJD the eyes have it, and it could be transplanted to you 28 Nov 99


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

Surgical & Endoscopic
Patients To Be Screened
For CJD Risks

http://www.rense.com/general73/screened.htm


http://www.vegsource.com/talk/madcow/messages/91334.html

ADDITIONAL DEBATES OVER THE YEARS ON THIS ISSUE ON CJD VOICE, you'll have to log in...tss



these findings _should_ now warrant complete attention to sporadic CJD and the medical and surgical arena, and this myth of the nv/v CJD/BSE ONLY thoery should be put to rest...TSS

some history on the topic of sporadic CJDs and Endoscopy Equipment ???


From: "Terry S. Singeltary Sr." >

Date: Sat Nov 30, 2002 11:13 am Subject: Fears over risk from surgical instruments--ENDOSCOPY EQUIPMENT ETC...


http://health.groups.yahoo.com/group/cjdvoice/message/22929



From: "Terry S. Singeltary Sr." >

Date: Tue Mar 5, 2002 10:37 am Subject: Re: [CJDVoice] sporadic CJDs and Endoscopy Equipment ???


http://health.groups.yahoo.com/group/cjdvoice/message/20647



From: "Terry S. Singeltary Sr." >

Date: Thu Mar 7, 2002 1:03 pm Subject: ever want to be a fly on the wall??? ENDOSCOPY's AND CJD's or any TSE


http://health.groups.yahoo.com/group/cjdvoice/message/20663



From: "Terry S. Singeltary Sr." >

Date: Mon Aug 27, 2001 2:51 pm Subject: Re: [CJDVoice] CJD AND ENDOSCOPY EQUIPMENT -- (RUBBERS FOR ENDOSCOPES) 'BRILLIANT' just need to use them...


http://health.groups.yahoo.com/group/cjdvoice/message/18796



From: "Terry S. Singeltary Sr." >

Date: Sat Aug 25, 2001 11:59 pm Subject: Re: [CJDVoice] CJD AND ENDOSCOPY EQUIPMENT -- Creutzfeldt-Jakob: all endoscop...

Re: [CJDVoice] CJD AND ENDOSCOPY EQUIPMENT -- Creutzfeldt-Jakob: all endoscop...

remember, no 'documented' cases of vCJD from surgical instruments (yet), and there have been 'documented' cases of sporadic CJDs from different surgical instruments/procedures...

TSS

mariek43@... wrote:

Remember that the US is only dealing with sporadic CJD and not the vCJD which has been found in the lymph tissue.

Marie

http://health.groups.yahoo.com/group/cjdvoice/message/18786



Thu Jun 28, 2001 10:39 pm

Re: [CJDVoice] sporadic CJDs and Endoscopy Equipment ???

hello Marie,

could you please pass reference to where w.h.o. states no need for special treatment for endoscopy equipment for patients of risk of CJD/TSEs. please pass document or url 'reference' please...

i understand about the fear factor, but some of these same folks are the ones that used to say BSE could not transmit to humans.

it would seem since there is documented iatrogentic case of sporadic CJDs, then this route could pose risk as potential route...

thank you, Terry

mariek43@... wrote:

For everyone's information !! I recently returned from my infection control conference and they presented new guidelines which recommend that endoscopy equipment does not need special treatment for CJD patients. This is consistent with the WHO guidelines. Remember it is good to search for information but detrimental to cause

unneccessary trauma for patients and their families. I know because I fight every day to quell the fear.

Marie

http://health.groups.yahoo.com/group/cjdvoice/message/18077

JULY 2006

ANNEX J

ASSESSMENT TO BE CARRIED OUT BEFORE SURGERY AND ENDOSCOPY TO IDENTIFY PATIENTS WITH, OR AT RISK OF, CJD

Categorisation of patients by CJD risk and infection control guidance

J1. There are special infection control precautions that should be taken in healthcare for patients with or at risk of CJD and Part 4 of this Guidance provides advice on this. This includes the risk categorisation of patients, given in paragraphs 4.16 – 4.17 and Table 4A of Part 4.

J2. In brief, when considering measures to prevent transmission to patients or staff in the healthcare setting, it is useful to make a distinction between symptomatic patients and asymptomatic patients as below:

Symptomatic i.e.


�� Patients who fill the diagnostic criteria of definite, probable or possible CJD and other human TSE (including sporadic CJD, sporadic fatal insomnia, variant CJD, iatrogenic CJD and familial disorders such as familial CJD, Gerstmann-Straussler-Scheinker Disease and fatal familial insomnia); and,


�� Patients with neurological disease of unknown aetiology where the diagnosis of CJD is being actively considered.

Asymptomatic patients i.e. those with no clinical symptoms, but who are identified as potentially at risk of CJD because of either:


�� Their family history, or;


�� Iatrogenic exposures.

The need to ask CJD risk questions as part of pre-surgery assessment

J3. It is essential that clinicians ask CJD risk questions to all patients about to undergo a surgical or endoscopic procedure that may involve contact with tissues with high or medium level infectivity, such as brain, spinal cord, eye, olfactory epithelium, spleen, tonsil, gastrointestinal lymphoid tissue and other fixed lymphoid tissue, as part of the pre-surgery assessment. Please refer to Part 4 and Annex A1 for further advice on surgical procedures and CJD tissue infectivity and Annex F for advice on endoscopic procedures. If effective pre-surgery assessment is not carried out, there is a danger that the CJD status of a patient will not be determined and this may result in failure to take the appropriate infection control precautions. If this is the case, there is the potential for a CJD incident to occur and this may result in exposing subsequent patients to CJD infectivity.

Recommended CJD risk questions

J4. A local level policy should be put in place to ensure that patients with or at risk of CJD are identified before surgery and therefore to allow the appropriate infection controls to be followed. To facilitate this, a list of recommended questions based on the information given in Table 4A is given in Table J1 below. It is recommended that patients are asked these questions prior to elective or emergency surgical procedures likely to involve contact with tissues of potentially high or medium level infectivity.

Published: 31 July 2006

Table J1 – CJD Risk Questions for patients about to undergo elective or emergency surgical procedures likely to involve contact with tissues of potentially high or medium level infectivity (please refer to Part 4 and Annex A1 for further advice on surgical procedures and CJD tissue infectivity):

Question to Patient
Notes to clinician

1
Have you any history of CJD or other prion disease in your family? If yes, please specify.
Patient should be considered to be at risk from familial forms of CJD linked to genetic mutations if they have or have had:

i) Genetic testing, which has indicated that they are at significant risk of developing CJD or other prion disease;

ii) A blood relative known to have a genetic mutation indicative of familial CJD;

iii) 2 or more blood relatives affected by CJD or other prion disease.

2
Have you ever received growth hormone or gonadotrophin treatment? If yes, please specify whether the hormone was derived from human pituitary glands?
Recipients of hormone derived from human pituitary glands, e.g. growth hormone or gonadotrophin, have been identified as potentially at risk of CJD. In the UK, the use of human-derived growth hormone was discontinued in 1985 but human-derived products may have continued to be used in other countries.

3
Have you had surgery on your brain or spinal cord before August 1992?
People who underwent neurosurgical procedures or operations for a tumour or cyst of the spine before August 1992 may have received a graft of dura mater, and should be treated as at risk, unless evidence can be provided that dura mater was not used.

4
Have you ever been contacted as potentially at-risk of CJD for public health purposes? If yes, please specify.
The CJD Incidents Panel has identified a number of individuals who are potentially at risk of CJD or vCJD for public health purposes (see paragraphs J8- J12 for further details).


The need for comprehensive pre-surgery assessment

J5. In addition to asking the patient CJD risk questions, the following actions should also be carried out before any surgical procedure involving tissues with high or medium level infectivity to ensure that a comprehensive pre-surgery assessment is carried out. The clinician undertaking the pre-surgery assessment should:


�� Check the patient’s medical notes and/ or referral letter for any mention of CJD status.


�� Consider whether there is a risk that the patient may be showing the early signs of CJD. i.e. consider whether the patient may have an undiagnosed neurological disease involving cognitive impairment or ataxia.

Published: 31 July 2006

These actions, in conjunction with the CJD risk questions, will minimise the chance of a CJD incident occurring and therefore greatly reduce the risk of transmission of CJD to subsequent patients.

Emergency Surgery

J6. In the event that a patient about to undergo emergency surgery is physically unable to answer questions, the next of kin should be asked the CJD risk questions before surgery takes place. If this is also not a viable option, the questions must be answered as soon as possible after the operation by either the patient or next of kin.

Training

J7. Trusts should ensure that the healthcare workers conducting the pre-surgery assessment receive the instruction and/or training necessary to understand the underlying reasons for asking these questions. It is crucial that the questions are asked in a manner that does not cause undue anxiety and therefore the questioner should be prepared to reassure the patient and provide further information, if needed.

Patients at risk of CJD for public health purposes

J8. As outlined in Table 4A in Part 4, a number of patients have been identified as potentially at risk for public health purposes on the recommendations of the CJD Incidents Panel. Paragraphs J9 to J12 provide some further information on these individuals and the steps taken to ensure that medical staff is informed of their risk status.

J9. This group of patients includes individuals identified to be at risk of:

a) CJD/vCJD due to exposure to certain instruments used on a patient who went on to develop CJD/vCJD, or was at risk of vCJD;

b) CJD/vCJD due to receipt of tissues/ organs

c) vCJD due to receipt of blood components or plasma derivatives;

d) vCJD due to the probability they could have been the source of infection for a patient transfused with their blood who was later found to have vCJD.

J10. When someone is notified that they are at risk of CJD, they are asked to take certain precautions to reduce the risk of spreading the infection to others. These include:


�� Not donating blood, tissue or organs;


�� Informing medical carers if they need to undergo an invasive medical procedure;


�� Informing their next of kin, in case they need emergency surgery in the future.

J11. The individual’s GP is asked to record the patient’s CJD at-risk status in their primary records. The GP should also include this information in any referral letter should the patient require invasive medical procedures.

J12. Further information on the work of the CJD Incidents Panel is available on the HPA website, http://www.hpa.org.uk/infections/topics_az/cjd/menu.htm

Published: 31 July 2006

http://www.advisorybodies.doh.gov.uk/acdp/tseguidance/tseguidance_annexj.pdf

2006/054 New NICE guidance to reduce the risk of transmission of Creutzfeldt-Jakob disease (CJD) via surgical procedures
22 November 2006
(46.2Kb 16sec @ 28.8Kbps)

Issued Wednesday 22 November 2006

Mid City Place

71 High Holborn


London

WC1V 6NA

Tel: 020 7067 5800


Fax: 020 7067 5801


nice@nice.org.uk


www.nice.org.uk


Ref: 2006/054

PRESS RELEASE

New NICE guidance to reduce the risk of transmission of Creutzfeldt–Jakob disease (CJD) via surgical procedures

The National Institute for Health and Clinical Excellence (NICE) has today issued guidance to the NHS on reducing the risk of transmission of Creutzfeldt–Jakob disease (CJD) via surgical procedures. NICE has recommended that:

• For certain surgical procedures carried out on the brain or eye (which carry a higher risk of potential transmission than other procedures):

�� Steps should be taken urgently to ensure that instruments do not move from one set of instruments to another. Practice should be audited and systems should be put in place to allow these surgical instruments to be tracked

�� Supplementary instruments that are used in these procedures should either be single use or should remain with the set to which they have been introduced

�� A separate pool of new reusable surgical instruments should be used for children born since 1 January 1997 (who are unlikely to have been exposed to BSE in the food chain or CJD through a blood transfusion) and who have not previously undergone these procedures

• For neuroendoscopy, a procedure using a tube inserted into the brain :

Page 1 of 3 Page 2 of 3

�� Rigid neuroendoscopes should be used whenever possible. They should be of a kind that can be autoclaved (steam cleaned at a high temperature and pressure) and they should be autoclaved after each use.

�� All accessories used through neuroendoscopes should be single use


�� A separate pool of new neuroendoscopes should be used for children born since 1 January 1997


• For all other surgical procedures, the risk of possible transmission of CJD is so low that it does not justify a change to single-use instruments.


Professor Peter Littlejohns, Clinical and Public Health Director at NICE and Executive Lead for this guidance says: "CJD is a terrible disease but thankfully it is extremely rare. This guidance is still important however, in order to help reassure the public that everything possible is being done to keep this risk as low as possible whilst also ensuring that surgeons have clear guidance."


Professor Bruce Campbell, Surgeon and chair of the committee who developed the guidance on behalf of NICE said: "Our guidance recommends two really important and practical measures for minimising the risk of CJD being spread by operations that NHS Trusts should implement immediately. The first is to be sure that all surgical instruments remain in their sets. The second is to check that systems are properly in place to track all instruments, so we know that they have stayed in their sets and we know which patients they have been used on."


Commenting on the use of single use instruments for surgical procedures, Professor Campbell continues "NICE has carefully considered the idea of introducing single use instruments for a whole range of operations. The problem is that single use instruments simply don’t exist for many operations. They take time to design and produce and they have to be of very high quality, otherwise patients may be harmed. We have also had to bear in mind that effective methods for removing CJD infectivity from instruments are likely to be available and widely introduced within 5 years. Therefore our recommendations for changes in practice have to be both practical and achievable within a short time frame."

Lester Firkins, lay member of the CJD Advisory Committee says: "As someone whose son died from vCJD, I consider even one preventable death to be one too many. There are so many uncertainties around this disease and whilst the only way to remove all risk is to destroy every single instrument after every single intervention, I understand that in practice this is unachievable. I have been fully involved in the NICE review process throughout and am comfortable that the final guidance fully takes into account the best research evidence as well as the cost implications for the wider NHS."

Page 3 of 3

The full guidance, which includes a list of all the surgical procedures covered by the guidance can be found on the NICE website at www.nice.org.uk

Ends

Notes for editors

About NICE

1. The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.

2. NICE produces guidance in three areas of health

• public health – guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector

• health technologies – guidance on the use of new and existing medicines, treatments and procedures within the NHS

• clinical practice – guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

http://www.nice.org.uk/download.aspx?o=387397

Patient safety and reduction of risk of transmission of Creutzfeldt-Jakob disease (CJD) via interventional procedures: Comments and responses on the second consultation
21 November 2006
(151.4Kb 01min 53sec @ 28.8Kbps)

http://www.nice.org.uk/download.aspx?o=387378

http://www.nice.org.uk/page.aspx?o=387378

TSS




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