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From: TSS ()
'In the hands of God' Greg's sense of humor and selfless attitude persevered until the end, loved ones say. Those who knew Greg best say he lived his life according to his heart's desires, mastering the endeavors he enjoyed most. He was a family man, a master dentist, a guitar player, a hockey booster and a sharp-shooter. ''He never denied himself anything,'' his wife, Lynne, says. ''He balanced his band, his work, the gun club. He loved his practice, his patients, and he did what he loved.'' Says brother Michaell Bever, of Atlanta, Ga.: ''He was focused on his family, his kids and his wife.'' He made time for others, leading groups of kids on Jet-Ski outings, or taking in relatives who needed temporary shelter. ''I never have known any human being that is so generous,'' Michaell says. Molly Ballor, who's been office manager for Bever's practice for 22 years, says the staff at the bustling practice was part of his family, too. ''We feel like we've been kicked in the stomach,'' she said Tuesday. ''But we're doing what he'd want us to do: We're taking care of our patients.'' nnn When Greg returned from the Mayo Clinic less than a month ago, word spread about the gravity of his condition, and well-wishers came calling at a rate of 30 to 40 a day. Page 2 of 10 ''He was a special guy, very happy-go-lucky guy, and everybody liked him,'' Zsenyuk says. ''We used to play jokes on each other, and it was even better if there was a third party befooled.'' The two friends didn't speak of the illness during their final visit. ''It was just amazing to see him surrounded by so much love, from his family, his extended family,'' Zsenyuk says. ''I gave him a guitar pick that said 'We'll be friends forever.''' The outpouring from friends and neighbors did not let up. Greg was touched by the displays of friendship, but retained his levity. ''He turned to me and said, 'Lynne, this funeral is taking too long,''' says his wife of 26 years. It's that sense of humor that's helped Greg and his family - which includes Gregory Jr., 19, a sophomore at Albion College; and All Saints students Alyson, 16, and Ian, 14 - face the grim diagnosis with grace. ''They're strong,'' Lynne says. ''They'll get through this.'' nnn Page 3 of 10 The diagnosed disease was ''sporadic,'' which means it was not caused by anything that researchers have been able to pinpoint. It is not contagious. Most patients live less than a year after diagnosis, experts say. For some unknown reason, proteins in CJD patients' brains fold in upon themselves, becoming something doctors call ''prions,'' and eat away at the healthy brain tissue. Saturday, discussing her husband's illness with a Times reporter, Lynne held a brain-scan transparency up on a living room window overlooking the Saginaw Bay. ''You can see it so clearly when you know what you're looking for,'' she says, indicating porous-looking edges and an almost triangle-shaped white spot on the brain's right lobe. ''It turns brain tissue into sponge.'' nnn Looking back, Lynne says, Greg's first symptoms probably appeared during a 10-day sailing trip to the British Virgin Islands in January. The first three days of the trip marked the first time the couple vacationed apart from their children since the first one came along 20 years ago. Then the entire crew of family and friends arrived, and the group chartered three sailboats for a weeklong Caribbean island-hopping adventure. The sailing was rough, the weather hot, and the sleeping quarters were cramped. ''Greg's job was to man one side of the ropes, something he's done many times before,'' Lynne says. ''But he really couldn't do it. He'd loosen when he was supposed to tighten, or tighten when he was supposed to release. I thought, 'Wow, this lack of sleep is really affecting him.' He just kind of laughed it off.'' After returning to Linwood, Greg canceled his dental appointments and tried to get some rest. Page 4 of 10 Doctors there said Greg had suffered a stroke. But his symptoms grew worse. He was sleeping 20 hours a day. He began having odd twitches and spasms, first with a thumb, then the whole hand. His arm torqued wildly one day when he and Lynne were sitting on the couch. ''What just happened?'' he asked her. By early February, Greg's weight loss had reached 30 pounds. But a doctor assured the Bevers that within weeks, maybe months, he'd be back to normal. After a Valentine's Day return to Beaumont, where more tests and a change of medication were ordered, Lynne says she became a bit pushy. She wanted an answer. She wanted her husband well. The doctors said they had nothing more to offer. nnn One day toward the end of February, Lynne took Greg to the emergency room in Midland. A neurologist told Lynne that the lesion on the left side of Greg's brain was not from a stroke. ''It could be Creutzfeldt-Jakob disease,'' the neurologist said. Page 5 of 10 Lynne packed her bags with two weeks of clothes. Surely, she thought, it's something else. Maybe Parkinson's, something curable. Or at least treatable. ''They were going to find out what was wrong with him, and he'd get some intensive rehab,'' she says, recalling her mindset as she made plans to go to Minnesota. When they arrived in Rochester, they were met by a man who'd been arranged by Lynne's employer, AstraZeneca Pharmaceuticals, to rush them to the hospital. Greg's stiffness and uncontrolled movements had grown worse. ''Doctors and nurses were all over him, like something from a movie,'' Lynne says. Doctors tried three different medications, to no avail. Greg spun and thrashed in the bed, asking ''What's happening to me?'' A day later, a brain scan led doctors at Mayo to diagnose CJD, Lynne says. It's fatal, doctors told them. There is no treatment, no cure. ''I guess it sucks to be me,'' Greg responded, mostly to break the tension in the room. Doctors were concerned about Greg's rapid deterioration. ''How close are your kids?'' one asked. Page 6 of 10 A few phone calls later, the Bever children, along with Lynne's brother, John Zessin were on a small plane, piloted by one of Greg's dental patients and family friend Mark VanBenschoten. Through snow squalls, they sped across Lake Michigan toward their father. The teens already knew their dad was sick. ''What you don't know is that there's no cure for this disease,'' the doctor said. ''He's going to die.'' The tears came, and then the hugs. And these words from Lynne, words that the family has lived by since. ''This disease is so rare,'' she said, ''let's look at it as a gift.'' ''We have time to say good-bye. Just think, if he was killed in a car accident on the way home from work one day, we wouldn't have been given this time.'' And so the good-byes began, the teens taking turns having time alone with their dad in the hospital room. ''Fourteen years was not enough time to have together,'' Ian told his dad. ''Buddy,'' Greg said, ''if I had 40 more years to spend with you, that still wouldn't be enough.'' Page 7 of 10 The return trip was arduous. Greg was so stiff, Lynne says - ''basically, 180 pounds of immovable man'' - he had to be loaded into his seat through the cargo door. Before leaving Rochester, Lynne called a friend who's a state trooper, asking if he could line up a stretcher. When they arrived at the airport, an ambulance and three attendants were waiting to take Greg home. When he saw the hospital bed they had waiting for him, he wanted no part of it. ''I'm not using that,'' he said. He never did. nnn The dentist started a rock band at the age of 44, when he and three friends formed the classic-oldies group The Sinclairs. ''It was his vision and passion for oldies music that led us to start the band,'' says guitar player Rod Loomis, of Midland. ''His vast library of nostalgia, facts, dates, and details for '60s music... The man was a walking library. He was amazing.'' The band, including drummer Ken Gloss and singer Dennis Beson, worked up a set of such standards as ''Secret Agent Man'' and ''I Fought the Law.'' They grew popular, playing up to 15 weekends a year. Page 8 of 10 Greg's ''guitar room'' is where he'd practice, with a half-dozen classic instruments housed among an array of memorabilia of the Beatles, his favorite band. The last time Greg picked up a six-string - as the illness was taking hold - he came back downstairs, disgusted. ''He said he couldn't find the chords,'' Lynne says. Shooting was another of Bever's passions. A member of the Linwood-Bay Sportsman's Club, Greg earned titles in skeet-shooting and shared his passion by teaching newcomers the sport. An annual pheasant-hunting trip to South Dakota with brother Bruce each October was a 34-year tradition and a bright spot on Greg's calendar. ''We were hunting and motorcycle buddies,'' says Bruce, of Marietta, Ga. ''We made an awesome team.'' When someone suggests that Greg was a perfectionist, Michaell sets the record straight. ''No, that's not right,'' Michaell says. ''He's a person who believed in excellence. He didn't expect perfection from himself or from anyone. He's a man who knew the difference between perfection and excellence.'' ''But,'' adds Lynne, ''he was a master at everything he did.'' Page 9 of 10 Greg told a Times reporter in 1999 where his work-ethic came from. ''My mother always said if you're going to be a ditch digger, be the best ditch digger,'' Greg said. ''It's just a commitment to excellence. I think excellence is an attitude that pervades all through your life.'' nnn Lynne met Greg, a Plymouth native, at her father's dairy near Detroit when she was just 17. Greg, six years her senior, was completing a biology degree. They were married in 1980, and Greg graduated from dental school at Marquette University in Milwaukee, Wis., in 1984. Greg went into partnership with dentist Jack Dee in Freeland and a year later, opened his own practice in Linwood. ''From the very first day,'' Lynne says, ''he was booked three weeks out.'' The Bevers fell in love with Linwood, and bought a little place on the beach. They've since built a new house - a sunny brick-faced home with windows looking out on the bay. Greg bought out a small practice in Bay City, then, 15 years ago, merged the two offices into the current location, at 3926 Traxler Court, in Monitor Township. Page 10 of 10 nnn Greg's family will receive visitors from 2 p.m. until 8:30 p.m. today at the W.A. Trahan Funeral Chapel, 256 N. Madison. A prayer vigil is planned for 7 p.m. On Friday, the Rev. Robert DeLand will lead the funeral Mass at 10 a.m. at St. James Church, 710 Columbus Ave. Lynne recalls a bit of advice one of her friends offered shortly after Greg's diagnosis. ''I hope you're not trying to find an answer,'' the friend said. ''Because there is no answer to find.'' Lynne decided to waste no time with the torture of ''Why?'' ''It was in the cards a long time ago,'' she says. ''We've put it in the hands of God.'' - Crystal Harmon can be reached at 894-9643 or by e-mail at charmon@bc-times.com. http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4 http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4&thispage=2 http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4&thispage=3 http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4&thispage=4 http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4&thispage=5 http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4&thispage=6 http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4&thispage=7 http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4&thispage=8 http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4&thispage=9 http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4&thispage=10 Subject: SEAC Position statement vCJD and Endodontic dentistry -------------------------------------------------------------------------------- Position statement vCJD and Endodontic dentistry 1. The Department of Health (DH) asked SEAC to advise on the findings and implications of a preliminary risk assessment of potential vCJD transmission via endodontic procedures (dental procedures involved in the maintenance of dental pulp and the treatment of the pulp cavity) 1. This is particularly pertinent because of the large number of endodontic procedures undertaken in the UK. Background 2. There are no reported definite or suspected cases of vCJD transmission arising from dental procedures. However, prions are more resistant than other types of infectious agent to the conventional cleaning and sterilisation practices used to decontaminate dental instruments 2. Therefore, should dental instruments become contaminated from tissues in the oral cavity of infected individuals, there is a risk of transmission to subsequent patients. 3. A quantitative DH risk assessment 3, accepted by SEAC in 2003, considered two possible mechanisms for the transfer of vCJD infectivity via dental instruments: (i) accidental abrasion of the lingual tonsil, known to carry infectivity in vCJD cases; and (ii) contact with dental pulp that evidence from animal studies suggested may be infective. On the basis of the information available, the DH analysis suggested that the risk of transmission to individual patients via accidental abrasion of the lingual tonsil is very low. Furthermore, should dental pulp be infective, the risk of transmission via endodontic procedures, although higher, is also low. Although a very large number of dental procedures are conducted, the relative risk to public health from potential transmission via dental, compared with hospital, surgery was considered to be relatively low. 4. In 2006, SEAC considered a new preliminary risk assessment by DH of the risks of vCJD transmission via endodontic procedures, taking into account new information on decontamination of dental instruments, the potential infectivity of dental pulp, and the possible existence of subclinical vCJD carrier cases. Endodontic instruments 5. Evidence suggests that the files and reamers used in endodontic procedures are reused and are difficult to reliably decontaminate 4. Appreciable quantities of residual material remain adherent to the surface after normal cleaning and sterilisation 5. Thus, there is potential for transfer of dental pulp between patients undergoing endodontic procedures. vCJD infectivity in dental tissues 6. There are no data on vCJD infectivity in dental pulp. Although no abnormal prions were found in a study of dental tissues, including dental pulp, from vCJD cases 6, dental pulp includes blood and peripheral nerve tissue known to carry vCJD infectivity 7,8. In addition, appreciable infectivity has been found in the dental pulp of hamsters with hamster scrapie 9. Although it is possible that the peripheral nerve may only become infective close to, or after, the onset of clinical vCJD, inflammation may promote the propagation of prions 10. Thus, although the data are limited and indirect, it is reasonable to assume that the dental pulp of individuals subclinically-infected with vCJD may be infectious although the level of infectivity is unknown. Studies underway will provide direct data on the infectivity in dental tissues from vCJD cases. Subclinical carrier state 7. A study of humanised mice showed that vCJD infections may not always progress to clinical disease within the normal lifespan of the animals 11. Another study suggested that prion infections in mice that remain at a subclinical level can be transmitted to other mice, resulting in clinical disease 12. Thus, there is evidence to suggest that individuals infected with the BSE / vCJD agent may remain in a subclinical infection carrier state instead of developing vCJD. A discrepancy between prevalence estimates based on a survey of abnormal prion protein in appendix and tonsil tissue and data on vCJD cases supports this hypothesis 13. As no diagnostic test exists to identify such individuals, they could over the course of their lives be potential sources of numerous secondary infections arising from invasive medical or dental procedures. 8. The prevalence of subclinical infection in the UK population is uncertain. A recent estimate suggests the number of subclinical carriers may be of the order of several thousand 14. SEAC has strongly recommended that further studies to ascertain better the prevalence of vCJD infection be urgently considered 15. Transmission risks 9. The new DH analysis suggests that, on the basis that residual dental pulp on endodontic files and reamers is transferred relatively efficiently to patients on reuse, dental pulp is as infective as peripheral nerve tissue and a subclinical carrier population for vCJD exists, a self-sustaining vCJD epidemic arising from endodontic surgery is plausible. There are uncertainties about the efficiency of vCJD transmission via endodontic procedures, the vCJD infectivity of dental pulp and the existence of a subclinical infection carrier state. However, even if a self-sustaining epidemic were not possible, clusters of vCJD infections could arise from the use of instruments contaminated with the vCJD agent from endodontic procedures on infected patients. Interactions between this and other routes of secondary transmission, such as blood transfusion and hospital surgery, would make a self-sustaining epidemic more likely. Potential risk reduction measures 10. Endodontic files and reamers have a limited lifespan, restricting the number of possible secondary transmissions. Improving the effectiveness of procedures used to decontaminate dental instruments would reduce the risk of transmission. Restricting endodontic files and reamers to single use would prevent potential secondary transmission via these instruments. Conclusions 11. A preliminary risk assessment produced by DH suggests that vCJD transmission via endodontic dentistry may, under certain hypothetical but plausible scenarios, be sufficient to sustain a secondary vCJD epidemic. However, there are uncertainties around the data and assumptions underpinning the assessment. Research underway will address some of these uncertainties and allow the risk assessment to be refined. Once the research is complete and / or other data become available, the risks should be reassessed. A watching brief should be maintained. 12. It is unclear whether or not vCJD infectivity can be transmitted via endodontic files and reamers. However, given the plausibility of such a scenario and the large number of procedures undertaken annually, it would be prudent to consider restricting these instruments to single use as a precautionary measure. Since sufficiently rigorous decontamination of these instruments is difficult, single use of these instruments would eliminate this risk, should it exist. SEAC 1. Department of Health. Dentistry and vCJD: the implications of a “carrier state” for a self-sustaining epidemic due to endodontic dentistry. A Preliminary Risk Assessment. Unpublished. D. Everington,1 A. J. Smith,2 H. J. T. Ward,3 S. Letters,4 R. G. Will5 and J. Bagg6 Objective Knowledge of risk factors for variant CJD (vCJD) remains limited, but transmission of prion proteins via re-useable medical devices, including dental instruments, or enhanced susceptibility following trauma to the oral cavity is a concern. This study aimed to identify whether previous dental treatment is a risk factor for development of vCJD. Design Case control study. Methods Risk factor questionnaires completed by interview with relatives of 130 vCJD patients and with relatives of 66 community and 53 hospital controls were examined by a dental surgeon. Responses regarding dental treatments were analysed. Results We did not find a statistically signifi cant excess of risk of vCJD associated with dental treatments with the exception of extractions in an unmatched analysis of vCJD cases with community controls (p = 0.02). However, this result may be explained by multiple testing. Conclusions This is the first published study to date to examine potential links between vCJD and dental treatment. There was no convincing evidence found of an increased risk of variant CJD associated with reported dental treatment. However, the power of the study is restricted by the number of vCJD cases to date and does not preclude the possibility that some cases have resulted from secondary transmission via dental procedures. Due to the limitations of the data available, more detailed analyses of dental records are required to fully exclude the possibility of transmission via dental treatment. snip... DISCUSSION Many studies have searched for risk factors for the development of different types of CJD, such as diet, exposure to animals, surgical treatment, including dentistry, and occupational exposures. A retrospective case control study15 of 60 definite cases of sporadic CJD, occurring in Japan between 1975 and 1977 found no association with extractions of maxillary or mandibular teeth. An analysis of 26 sporadic CJD cases and 40 matched controls from the United States16 failed to discover a significant odds ratio for endodontic surgery, though these workers did note statistically significant odds ratios for intraocular pressure testing, injury to or surgery on the head, face or neck and trauma to other parts of the body. However, these findings suffer from low statistical power and, in the case of the Japanese paper, information was requested for extractions only during the fi ve year period prior to onset. This paper attempts to identify an association between vCJD and reported dental treatment. Comparison of the reported dental histories of cases and controls found that extractions were the only dental risk factor that reached statistical significance (at the 5% level) in the unmatched analysis with community controls. This may be a result of multiple testing especially as there are fewer extractions in the cases than in the hospital controls. It is likely that the majority of vCJD cases in this cohort were infected through eating BSE contaminated meat products. Therefore, it is diffi - cult to detect a small subgroup that may have been infected by secondary transmission, as in this study, through dentistry. There are a number of limitations to this study, most importantly relying on reported data from relatives and the relatively small numbers of cases and controls resulting in low power to detect statistical differences. Recruitment of controls has been problematic,17 although every effort was made to maximise this group. Selection of controls was not matched for demographic and socio-economic factors for dental attendance and this may have resulted in bias. It is possible that some of the responses of ‘no known treatment’ reflect poor knowledge or recall on the part of the relatives. This would reduce the power of the study to pick up significant differences between groups, but not necessarily introduce bias. Whilst these preliminary data on a topic of great concern for public health do not provide evidence supporting reported dental work as being a major route of transmission of the BSE agent to humans to date, they do not preclude the possibility that some vCJD cases have been infected by this route. Furthermore, the incubation period following infection by a peripheral route may be relatively long and therefore the period of observation to date of potential secondary transmission of vCJD may be too short to detect cases. A more detailed study of previous treatment based on reviewing actual dental records rather than relying on reported treatments is required to gain a wider insight into the dental history of both cases and controls. We are currently investigating the possibility of examining dental records of vCJD cases and a larger group of unmatched controls.18 The National CJD Surveillance Unit is funded by the Department of Health and the Scottish Executive Department of Health. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or in the writing of the report. We are also grateful to the families of cases, without whose co-operation this study would not have been possible. FULL TEXT ; http://www.nature.com/bdj/journal/vaop/ncurrent/pdf/bdj.2007.126.pdf Subject: PrPSc in salivary glands of scrapie-affected sheep J. Virol. doi:10.1128/JVI.02148-06 Marta Vascellari*, Romolo Nonno, Franco Mutinelli, Michela Bigolaro, Michele Angelo Di Bari, Erica Melchiotti, Stefano Marcon, Claudia D'Agostino, Gabriele Vaccari, Michela Conte, Luigi De Grossi, Francesca Rosone, Francesco Giordani, and Umberto Agrimi Subject: CJD: update for dental staff 1: Dent Update. 2006 Oct;33(8):454-6, 458-60. CJD: update for dental staff. Scully C, It is almost a decade since the recognition of the emergence of a new infectious disease termed variant Creutzfeldt-Jakob disease (vCJD) caused by prions (PrPTSE), abnormal variants of a normal human cell surface protein (PrP).This disease has a number of similarities to other forms of CJD--lethal disorders characterized by a prolonged incubation period, and progressive mental deterioration. In relation to oral tissues, PrPTSE have been found in neural, gingival, pulpal, lingual, lymphoreticular and salivary gland tissue in animal models. In both sporadic and variant CJD, PrPTSE is detectable in the trigeminal ganglion and, in vCJD, in lymphoreticular tissues, but infectivity has not been tested in other human oral tissues. CLINICAL RELEVANCE: PrPTSE is much more resistant to the common methods of inactivation than conventional pathogens, and it adheres avidly to steel whilst retaining its infectivity. Particular attention must be paid to cleaning and sterilizing re-usable dental instruments. Single-use devices, such as endodontic files and matrix bands, must never be re-used. Advice on the reprocessing of dental instruments used on known CJD patients must be obtained from local infection control teams. Research into effective methods of prion inactivation appears promising, although further work on the applicability to general dental practice is required. PMID: 17087448 [PubMed - in process] 64. A member noted that at the recent Neuroprion meeting, a study was Other work presented suggested that BSE and bovine amyloidotic spongiform http://www.seac.gov.uk/minutes/95.pdf Models Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain ***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than There is a growing number of human CJD cases, and they were presented last He estimates that it may be up to 14 or 15 persons which display selectively Chronology 1988 30. I cannot recall now when I first became aware of the new bovine disease but on the 16th November 1988 I attended the CDSM to present two papers on dental products [YB88/11.16/6.1-6.7]. At that meeting and the Committee noted a paper which provided a background to the problem of BSE (YB88/5.13/9.1). 1989 31. On the 15th March 1989 [YB89/3.15/7.1-7.3], I attended the CDSM because there were two items (items 11 and 23) on the agenda of dental interest which I had prepared papers for. 32. At this meeting the Joint CSM/VPC Guidelines [YB89/3.00/1.2] for Industry paper relating to BSE was noted and the Southwood Report IBD 2[vol IBD1, tab 2] was given to members to take away [YB89/3.15/7.2]. 33. On the 16th March 1989, I wrote to Dr Adams (Principal Medical Officer, Medicines Division with overall responsibility for the review of medicines and the CDSM) [YB89/03.16/8.1]. I had read the Joint CSM/VPC Guidelines [YB89/3.00/1.2] and asked for an explanation of the sterilization guidelines which were in excess of the Department of Health guidelines for sterilisation of unwrapped instruments. The length of time in the Joint Guideline for autoclaving using a porous load cycle at 134-138 degrees was 18 minutes instead of the usual minimum of 3 minutes. 34. I suggested to Dr Adams in that minute that in view of the comments that were made with regard to the undesirability of harvesting human dura, this had implications for the sterilization of all instruments used routinely for cranial surgery. Because the Joint CSM/VPC Guidelines for Industry were to be sent to overseas manufacturers, I questioned whether the units for pressure should have been expressed in the international SI (Standard International) units. 35. Dr Adams in his minute dated the 21st March 1989 [YB89/03.21/15.1], stated that the sterilization details were provided by MAFF at the Central Veterinary Laboratory and seen by the Expert Working Group on BSE. He stated that advice along similar lines had been issued to the NHS in 1981. There had been a number of well documented cases where CJD had been transmitted via the use of contaminated instruments. He stated that he was sure that these cases would be known to neurosurgeons. 36. I was minuted by Dr Pickles on the 17th April 1989 [YB89/4.1/5.1]. She mentioned some comments made by the Tyrrell committee when considering the CSM Guidelines and Dr Will’s concern in relation to topical dental products. I cannot recall whether I wrote in response to this minute. I believe that I took it to be a notification of the need for vigilance should dental products that had bovine actives/intermediates become available and application made for licenses. 1990 37. I attended the CDSM meeting on the 17th January 1990 [YB90/1.17/12.1-12.5] because applications for licences for dental products were being considered by the Committee. It was usual for assessors to be asked to report on anything of a general nature at the end of the discussions on papers. On this occasion the Committee were informed that an application had been received under the Committee for Proprietary Medicinal Products arrangements and the UK would be taking the lead. This was an arrangement whereby a simultaneous application for a product licence could be made by a company to a number of European Countries. The Committee was advised that it would have to consider this application later in the year. 1991 38. At the Meeting of the CDSM held on 20th November 1991 [YB91/11.20//6.1-6.4] I presented my assessment of a product consisting of a mixture of bovine derived collagen and hydroxyapatite for the augmentation of deficient alveolar ridges. CDSM were unable to advise the grant of a product licence. 1993 39. I attended the meeting of the CDSM held on 21st July 1993 [YB93/07.21/4.1-4.7] to present the assessment of a collagen based product. The Committee were unable to advise the grant of product licence. 40. On 13th September 1993, Mr Eaton, another Senior Dental Officer (with responsibility for hospital dental services and postgraduate and continuing dental education) minuted me [YB93/9.13/2.1] in relation to a request he had received from Dr Ailsa Wight which required comment on an CJD article in the Daily Express dated 4th September [YB93/09.04/3.1]. Mr Eaton had contacted a Professsor of Dentistry who stated that it was most unlikely that treatment procedures in General Practice could be responsible for transmission of CJD. He asked me to comment on a brief paper about CJD which had been prepared by Dr Wight. 41. On the 14th September 1993 I minuted Dr Ailsa Wight (Senior DH medical officer and SEAC Observer) [YB93/09.14/5.1]. I wrote that it seemed extremely unlikely that a dentist in General Practice could infect patients with CJD virus. This statement was based on the fact that human dura was not used in general dentistry but had been used in specialised oral surgery which would not be carried out by a dentist in general practice. 42. I also informed Dr Wight that collagen sponge of bovine origin was commonly used at one time as a haemostat following dental extractions. I stated that as far as I was aware, no such dental products were licensed in the UK at that time. 43. I was able to give the advice in this minute from knowledge of what constituted the general practice of dentistry, knowledge of dental products which I had gained from my work as a general practitioner and as a senior dental officer which involved keeping "up-to-date" with dental practice. 44. On the 28th September, Mr. Gordon had written to Dr Wight in relation to a proposed BDA publication [YB93/09.28/3.1-3.3]. Dr Wight sent me her draft reply to Mr Gordon and I made two minor comments in a minute dated 1st November 1993 [YB93/11.01/5.1]. I recommended that her reply should include a suggestion that the BDA paper on Iatrogenic Creutzfeldt-Jakob Disease, should include there were other good reasons for considering many endodontic instruments as single use items and for limiting the number of times others might be re-used. 45. I remember that these reasons included the fact that re-sterilization of these instruments might affect the physical properties of the instrument. The re-sterilization might increase the chances of fracture of such instruments in the root canal. This would have given rise to considerable difficulty in achieving a satisfactory result as far as a patient was concerned. There were other amendments and according to letters I was copied, the BDA publication was amended by Mr Gordon [YB93/11.17/5.1-5.4]. 1994 46. I left the Department of Health in May 1994. Relevant interests 47. I have no links past or present with the farming community, renderers, feed stock manufacturers, pet food manufacturers, trade associations. During my time at the Department of Health I had contact with pharmaceutical companies in a solely professional capacity. Since leaving the DH, I have done part time consultancy work for a number of manufacturers who produce dental products though none have been involved with products of bovine origin. 48. This Statement is true to the best of my knowledge and belief. Issued on behalf of the witness by: The BSE Inquiry Press Office 6th Floor Hercules House Hercules Road London SE1 7DU Fax: 0171 803 0893 Website: http://www.bse.org.uk http://www.bseinquiry.gov.uk/files/ws/s549.pdf Possible occupational risks from TSEs Although CJD has been documented in a neurosurgeon, two neuropathology technicians, an orthopaedic surgeon and a pathologist, it is reassuring to note that in none of these individuals was there a history of a definite infective event. The orthopaedic surgeon had however worked with human and ovine dura mater 20 years prior to his illness. Case-control studies do not suggest that individuals potentially exposed to the TSE agent in the health care setting are at an increased risk of developing CJD. However, the possibility that cases of CJD have rarely occurred in such circumstances cannot be confidently dismissed. A statistically significant excess of cases of CJD in cattle farmers has been reported in the UK since 1990. Of concern, four of these six cases were known to have had BSE-affected animals in their herds. However, analysis of the clinical and pathological features of these cases showed that none had the nvCJD phenotype. This observation has been strengthened by recent molecular biological data that demonstrated that the PrP glycosylation pattern characteristic of both BSE and nvCJD was not present in any of these cases. Furthermore analysis of the incidence of CJD in dairy farmers from other European countries, in which BSE is rare or absent, reveals a similar excess of cases. This observation suggests that dairy farmers may be at increased risk of CJD for reasons other than exposure to the BSE agent. One possible explanation for the apparent excess of cases in dairy farmers, particularly in the UK, is that case ascertainment in this group has been better than in other groups because of concern of a possible link between the bovine and human diseases. SECTION 7: THE RISK TO PATIENTS UNDERGOING DENTAL TREATMENT It is of great concern that there may be a risk of becoming infected with nv-CJD in the dental surgery due to cross infection from either the dentist or another patient. The two main sources of infectious material in the dental surgery are blood and saliva. As shown in Table 7 these are of relatively low infectivity compared to the tissues of the CNS. As nv-CJD has only recently been discovered, few experiments have been carried out to discover whether it can be transmitted. Therefore, we must look at the other TSEs to get an indication of likely risk. The risk of transmission via saliva Studies to ascertain levels of PrP have shown that salivary gland tissue contains high levels of infectivity, much earlier than in brain tissue (Sakaguchi 1993, Eklund 1967). Replication of the infectious agent first appears in salivary tissue soon after inoculation, possibly indicating that the salivary glands are one of the primary sites of replication, rather than the brain. It was also found that infectivity declines with time, suggesting that greatest risk from transmission is likely to be early in the disease, before clinical signs are present. There has been no research into the risk of transmission from saliva, however we must assume that if salivary gland is infected then so is the saliva it produces. The effect of gingival scarification on transmission If it is found that BSE has been transmitted to humans via the oral route it is essential to ascertain any factors that may have increased susceptibility and therefore may have implications for human to human transmission. Studies into the effect of gingival scarification on the transmission of Scrapie (Carp 1982) have shown that a higher proportion of mice succumbed to infection if their gingivae had been scarified compared to the controls (100% and 71% respectively). It was also shown that the incubation period was significantly shorter. Although it has not been possible to transmit Scrapie using dental burs (Adams 1978) it was found that the gingivae of infected mice do contain a low level of Scrapie infection that can be transmitted using an intra-cerebral approach. The risk of transmission via blood products Although most forms of CJD have been considered infectious by the mid-1960s its transmissibility through the use of blood products is still controversial. Sporadic CJD has been reported to be transmitted to mice by injecting blood from human patients directly into mouse brain (Brown, 1994, Manuelidis, 1985). However this evidence has not been reproduced and another review of research with non-human primates indicated that sporadic CJD-infected human blood did not transmit the disease to primates (Tateishi, 1985). Some evidence indicates that blood of experimentally infected animals contains an infective agent. PrP infectivity resides predominately or exclusively in lymphocytes and monocytes rather than granulocytes (Lavelle, 1972). There has been no evidence of infectivity in erythrocytes, platelets or plasma, but low infectivity cannot be excluded. Animal studies have demonstrated that the scrapie-agent replicates first in the spleen and other lymphoid tissues but reaches the highest concentration in the brain, where it results in the clinical appearance of the disease (Kurudail 1983). Hence, peripheral tissues in contact with blood also harbour PrP infectivity. Animal transmission data indicate that human spleen, lymph nodes, serum and cord blood are irregularly infective for animals, although few cord blood samples have been tested (Manuelidis, 1979). Studies of experimental sporadic CJD in guinea pigs and mice have shown that the infectious agent is present in the brain, viscera and blood before clinical disease develops (Lavelle, 1972 & Czub 1986). Several factors must be considered in reviewing the animal evidence regarding transmission of human TSEs in blood: the type of human TSE being tested, the level of PrP infectivity of the study tissue, the species barrier, and the route of transmission. The evidence from animal studies is inconclusive regarding transmission of sporadic CJD between humans by transfusion. Although case reports have provided evidence linking CJD to the receipt of dura mater and human growth hormone, no human cases have yet been causatively linked to blood transfusion. A number of cases have been seen where patients have undergone organ transplant and then developed CJD. It is, however, impossible to determine whether the organ was the source of the infection as insufficient information about each case is available. If CJD is transmissible in blood, cases should occur in young patients, particularly if the incubation period is short as in the other iatrogenic cases. Even if the incubation period were many years, one would expect to see cases in young persons because of the transfusions given to infants and young children. If CJD is transmitted in blood, a detectable increase in cases in blood transfusion patients may be expected. There is a ban on the use and export of blood and blood products from the UK (February 1998) as a precautionary measure and for the past two years any donor with a family history of CJD has been prevented from donating blood. However this may be unreliable, as many patients will not know the accurate diagnoses of a family member's illness. As noted by Brown (1996) in reference to blood products, "iatrogenic disease from this source would dwarf in importance all other sources by virtue of the sheer numbers of people who theoretically have been or could be at risk". The appearance of nvCJD raises new concerns. Due to a possible oral route of infection and a novel strain of agent, the distribution of tissue infectivity may differ from other forms of CJD. This is supported by evidence that suggested that at the palatine tonsil might harbour PrP in nvCJD but not in sporadic CJD. In view of the theoretical possibility that blood from patients incubating a TSE may harbour the infective TSE agent the World Health Organisation recommends that the following groups should be excluded as blood donors: · Recipients of extracts derived from human pituitary glands (growth hormone and gonadotropin). · Those with a family history of CJD, GSS or FFI. · Those who have received a human dura mater graft. Animal studies indicate that the infective agent of human TSEs is present in blood in low titres, and sufficient evidence of animal transmission suggests that the disease has the potential to be transmitted through blood (Heye 1994). However, to date, epidemiological evidence indicates that if blood transmission occurs it is likely to be rare. This may be due to polymorphism at codon 129, which could restrict susceptibility. It is also possible that most transfusions may not contain sufficient dose to cause infection. There is no specific scientific evidence to date that nv-CJD will transmit through blood products. This is due to the incubation period being many months in laboratory animals. As infectivity has only been detected in white blood cells the potential risk from donated blood can be decreased by a process known as leuko-depletion, removal white blood cells. The knowledge that blood may be infected could change the views of both the medical profession and patients. Transfusions may only be used if absolutely necessary and patients may be given the option of donating their own blood for scheduled operations. If CJD were transmitted in pooled blood products or saliva, clusters would be detected. Most clusters have usually been attributed to familial disease (Masters, 1979 & Reingold 1996). Surveillance systems have found cases of CJD among persons who have received blood transfusions but none have been linked to blood transmission. It must be remembered, however, that surveillance systems may not detect cases when unique epidemiological or clinical features are present. SECTION 8: CONCLUSIONS A number of factors must be taken into consideration when assessing the risk of transmission of nvCJD during dental treatment. Dental patients are at risk of infection from a number of sources, the most significant being the consumption of infected animal products during the 1980s. A small minority of patients will also be at increased risk in their place of work, such as neuropathologists, neurosurgeons and laboratory technicians. The most likely route of infection is via ineffectively sterilised instruments. If a patient is suspected of having or has been diagnosed with nv-CJD further precautions can be taken. The patient is likely to be showing clinical signs, which are likely to make dental treatment difficult, therefore only emergency treatment is going to be appropriate. Where possible, a treatment option that involves the least cross infection risk should be undertaken. . To reduce this risk, all instruments that have been used on a patient with nvCJD should be disposable or discarded. This includes oral surgery equipment, root planing hand instruments and ultrasonic tips in addition to needles and blades. In the case of accidental inoculation it is unlikely that sufficient infective material will be involved to transmit the disease. As discussed previously, the peripheral route of infection is ineffective compared with intracerebral inoculation, and blood or saliva contains little infectivity compared to central nervous tissue. All patients should be treated using universal precautions, which should be employed in all dental practices as a matter of routine, providing the maximum protection equally to clinical staff and patients. This includes the use of gloves, masks and eye protection at all times. After each patient all instruments should be autoclaved and disposable alternatives should be used where appropriate. The number of patients likely to be incubating nv-CJD is impossible to predict at present. Much depends on the average incubation time, the longer the time, the higher the figure is likely to be. At present the average incubation time can not be calculated nor is it possible to estimate the dose required to infect a human. With the possibility of a nationwide epidemic investigation must be carried out to determine the risk from cross infection. Research has yet to prove that there is a risk, however, until all possibility of this can be discounted caution must prevail. The resistance of the TSE agent to standard medical sterilisation procedures is noteworthy. Experimental evidence demonstrates that the agent shows resistance to the following: exposure to boiling, freezing, ethanol, H2O2, permanganate, iodine, ethylene oxide vapour, detergents, organic solvents, formaldehyde, UV and gamma irradiation, and standard autoclaving. Since conventional methods of sterilisation and disinfection do not decontaminate the CJD infectious agent, specific measures must be used, however, many of these are impractical in the dental practice. Although the TSE agent is known to be infectious it is not contagious in the usual sense. Individuals exposed to patients with CJD: their spouses, nurses and doctors, do not appear to have an increased risk of developing the disease. Furthermore, professionals who might be considered 'high risk' in relation to exposure to TSE agents: e.g. pathologists, neurosurgeons, butchers etc. also do not appear to be at an increased risk of developing CJD. No proven instance of CJD contracted occupationally has yet been identified. However, over 170 cases of iatrogenic CJD contracted through inoculation of contaminated CNS tissue or corneal transplantation serve to remind those of us involved in the management of all CJD patients of the importance of safety procedures in relation to the TSE agents. REFERENCES snip... http://www.bseinquiry.gov.uk/files/ws/s201a.pdf Date: January 18, 2007 at 8:32 am PST Editorial team (eurosurveillance.weekly@hpa.org.uk), Eurosurveillance editorial office References: http://www.eurosurveillance.org/ew/2007/070118.asp#4 RISK OF TSE VIA DENTAL AND NEED FOR CJD/TSE WRITTEN QUESTIONNAIRE http://neurotalk.psychcentral.com/archive/index.php/t-13173.html http://www.rense.com/general34/evi.htm http://brain.hastypastry.net/forums/showthread.php?t=2408 Diagnosis and Reporting of Creutzfeldt-Jakob Disease http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtos JOURNAL OF NEUROLOGY MARCH 26, 2003 RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 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? Singeltary, Sr et al. JAMA.2001; 285: 733-734. http://jama.ama-assn.org/ BRITISH MEDICAL JOURNAL EXPORTATION AND IMPORTATION OF ANIMALS AND ANIMAL PRODUCTS: http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0701&L=sanet-mg&T=0&P=3854 Terry S. Singeltary Sr.
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