Death of 26 year-old in NY
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Rochester death may be from mad cow
Guidance for lab and healthcare workers for TSE agents
Public Eye special on CJD airs in July
CJD hormone victims compensated
Texas and Australia: family experiences with CJD
Flupirtine: future CJD drug?
Hemophiliacs still at risk for CJD despite combinant product
Congress warned about US meat inspection
Dutch patients injected with recalled blood product
BSE groundwater risk said low
Lancet editor takes payoff to plant cigarette science?
Canada to try eyelid test on sheep
Toxins trigger Alzheimer's
French meat: too much dioxin from incineratation

Rochester death may be from mad cow

UPI US & World Wed, May 27, 1998
ROCHESTER, N.Y. -- The death of a Rochester, N.Y., woman may be the first mad cow disease fatality in the United States. Twenty-six year-old Stephanie Breitkopf will be buried today in Palmyra, N.Y., near Rochester, N.Y.

Lona and Stanley Breitkopf say their daughter was an intelligent, athletic and healthy student who attended Cazenovia College on a tennis scholarship before she got sick seven years ago. Lona recalls receiving a gift of beef from Great Britain in 1987, one year after the disease was first identified.

The degenerative illness baffled Stephanie's physicians, but two years ago, Dr. James Ghertner suspected mad cow disease. At first, the Breitkopfs thought their daughter had Alzheimer's disease, because she started acting strangely and forgot how to drive. The couple began to suspect mad cow disease was addling Stephanie's brain after watching a television program about the illness and its symptoms, conditions that matched the young woman's.

Stephanie's brain and spinal fluid samples are being sent to mad cow disease researchers.


The media has finally come out with this story. CJD seems to be suspected but it remains to be determined whether it will prove to be nvCJD. The victim was very young at onset, 19, and the course of illness was quite long, 7 years. There was some possible exposure to UK BSE but much less than many still-healthy people. It sounds like tests for 14-3-3, florid plaque, and glycoform ratios are being done.

There have been cases of CJD in the US in young people but they are extremely rare and mostly predated the modern testing era. --webmaster

More comments:

"There has not yet been a CJD diagnosis, to my knowledge, in the Rochester death. Material has been sent to Gibb [at NIH] and Prusiner [at UCSF] both. But no results yet."

A relative comments:

"The media give the wrong date of death and place of burial."

Revised guidance for laboratory and healthcare workers on safe working with TSE agents

20 May 98
Eileen Lawrence
Joint Secretary to the Advisory Committee on Dangerous Pathogens
Department of Health
80 London Road
London SE1 6LW
The full text of this guidance is available on The Stationary Office website.

Public Eye special on CJD airs Tuesday

25 May 98
The Bryant Gumble Public Eye show will air on June 24th, 1998. Nanci Ross (the producer) and Peter VanSant (the anchor) went to the UK to interview Dr. Ironside among others.

CJD hormone victims compensated

AP US & World Fri, May 22, 1998
LONDON -- The families of eight children who died from a brain-wasting disease after being treated with human growth hormones from cadavers can seek compensation from the British government, the High Court ruled Friday.

Twelve families have already received damages ranging from $146,700 to $228,200 following a similar 1996 ruling, and the latest claimants also are expected to win compensation, said David Body, one of the lawyers representing the current plaintiffs.

Twenty-five people in Britain who received the hormone have died of Creutzfeldt-Jakob Disease. While a new strain of CJD has been linked to infected beef from cattle with mad cow disease, the current court case involved CJD in its original form.

Between 1959 and 1985, nearly 2,000 children whose growth was stunted because of a hormone deficiency were treated in Britain with hormone from the pituitary glands of cadavers. The program was stopped after several children who had received similar treatment in the United States died of CJD.

In July 1996, High Court Judge Sir Michael Morland ruled that the British Department of Health was negligent in not heeding a doctor's warning in 1977 about the risk of contracting CJD from the hormone treatment.

He said the department should not have allowed any more patients to enter the program after July 1, 1977, and that families of those whose treatment began after that date could pursue compensation.

On Friday, Morland ruled that families of victims who entered the program before July 1, 1977, and continued afterward also could seek compensation because doctors should have stopped their treatment after the warning.

Morland is expected to rule in July on cases brought by six people treated with the growth hormone as children and now living in fear of contracting CJD. They are seeking damages for psychiatric illnesses.

Independent of Friday's ruling, a judge in March began a formal investigation into the government's handling of the animal form of mad cow disease, a crisis that devastated Britain's beef industry after evidence surfaced that the disease had spread to humans who had eaten the meat.

Triumph as victims of CJD error win cash fight

The Independent, London, May 23, 1998
Following a bitter battle, eight families have won the right to claim compensation for the death of relatives after a medical warning was ignored. By Ian Burrell, Home Affairs Correspondent

EIGHT families who lost relatives to CJD following treatment with human growth hormone yesterday won the right to claim compensation from the Government.

The High Court ruling signalled a triumphant end to a nine-year battle for the families who have submitted compensation claims totalling more than #1m. The finding is likely to pave the way for many more claims.

Between 1959 and 1985 nearly 2,000 British children whose growth was stunted because of a deficiency in the secretion of growth hormone in their pituitary glands were treated with hormone from the pituitaries of human cadavers.

Two years ago, the Department of Health was found negligent in not heeding the warning of Dr Alan Dickinson, who in 1977 told the Medical Research Council about the risk of contracting CJD from the hormone treatment. The ruling cleared the way for families of victims treated after 1 July 1977 to seek compensation. Yesterday Mr Justice Morland ruled that families of victims whose treatment "straddled" the compensation cut off date could also seek compensation.

After the ruling, Stephen Irwin QC, representing the families of 13 victims, said that the Department of Health would "no doubt" consider admitting liability swiftly "so as to relieve the minds of the families". Five of the families he represents have yet to have their cases determined.

Among the successful families yesterday was that of Saul Hefferon-Walden, who died of CJD at the age of 20 in 1988.

Saul, who was treated with growth hormone between the ages of seven and 17, first became sick while studying for his A-levels. His father, Don Hefferon, of Paddington, west London, said the family put his condition down to "the average young man's lifestyle of late nights, discos and drinking cider in the union bar".

Mr Hefferon said his son had been offered a place at the Anglia Polytechnic but found his concentration and writing becoming difficult.

"I feel more distressed than angry or bitter. I had always presumed the NHS was there to really care for people . in extreme distress, whatever their particular illness," he said. "I am very happy there has been this decision, but I am sad that not all people have been included in it."

Terence Newman, another CJD victim, died in December 1990 at the age of 21 following treatment with human growth hormone between the ages of six and 18. His mother Maureen Newman, 48, from Coulsdon, Surrey, said: "I am very pleased with the judgment, I just wish it had all finished a couple of years ago for us. Now we know we have won we can let Terry rest."

She stressed that, without legal aid, she could never have fought the case.

David Body, of Irwin Mitchell solicitors, representing the plaintiffs, said: "After the Department of Health was found negligent in 1996, our suggestion that all remaining cases be compensated was fought at every step . These families were fighting a government that refused a public inquiry and so had to seek their justice at court."

Leigh-Ann Mulchahy, counsel for the Department of Health, said: "My clients wish to have an opportunity to consider the judgment and consider whether or not they wish to appeal it in any way."

In a later judgment, expected in July, Mr Justice Morland will rule in test cases brought by six people who received the growth treatment and who live in fear of contracting CJD.

CJD victims' families awarded #1m

The Guardian, London, May 23, 1998  Saturday May 23, 1998 By Clare Dyer, Legal Correspondent
Eight families who lost relatives to Creutzfeldt-Jakob Disease (CJD) after treatment with contaminated human growth hormone won the right to government compensation totalling more than #1 million in the High Court yesterday.

The ruling brings to 20 the number who have won damages. They include parents, and spouses and children of CJD victims who died in their 20s and 30s as a result of treatment in childhood.

Five more cases are in doubt because full medical records cannot be found, and two were lost because the treatment was completed before the Government could have been expected to know the risk. David Body, the claimants' solicitor, called on the Health Secretary, Frank Dobson, to settle all the outstanding cases.

Nearly 2,000 children of short stature in Britain were given human growth hormone extracted from the pituitary glands of corpses between 1959 and 1985. Of those, 27 contracted CJD and all but two have died. An unknown number may still develop the disease, because scientists believe it may incubate for up to 30 years.

The eight families, who are each claiming damages of between #90,000 and #140,000, were originally told they were ineligible because their relatives' treatment began before July 1, 1977 - the date after which a court in 1996 ruled the Government knew the treatment carried a risk of causing CJD, but failed to inform doctors.

Mr Justice Morland originally decided doctors would not have stopped treatment for existing patients, even if they had known of the risk, although they would not have started new patients on it. But in yesterday's judgment, he said he had changed his mind after evidence >from four professors involved in the growth hormone programme. Families of those who started treatment after July 1, 1977 have already won compensation.

Lawyers for the families said they would meet representatives of the Department of Health on June 17 to try to agree compensation.

The programme was ended in May 1985 after the first reports of deaths from CJD in the United States. Risk-free genetically engineered growth hormone is now used.

In July 1996, Mr Justice Morland ruled that the Department of Health was negligent in deliberately keeping clinicians "in the dark" about warnings from scientists. Lawyers for the Department of Health said it would be considering whether to appeal.

Mr Body, of Irwin Mitchell solicitors, representing the families, said: "These families were fighting a government that refused a public inquiry three times and so had to seek their justice at court."

Don Hefferon, aged 69, of Paddington, west London, whose son, Saul, died aged 20, said: "I think that payment should be extended to all families that have been visited by this catastrophe."

He added: "I feel more distressed than angry or bitter. I had always presumed the NHS was there to care for people in extreme distress, whatever their illness. The official attitude has been callous and indifferent."

Maureen Newman, aged 48, from Coulsdon, Surrey, expressed relief with the ruling but said she had become "disillusioned in many ways" over the health service. Her son, Terence, died in December 1990 at the age of 21. He had been treated with human growth hormone from the age of six to 18.

She said: "Now we know we have won, we can let Terry rest."

A judge has swept aside a cut-off date to help eight families

 THE TIMES [London], May 23, 1998 Michael Horsnell
Families who lost relatives to Creutzfeldt-Jakob disease from contaminated human growth hormone won their eight-year legal battle yesterday for compensation expected to exceed #1 million.

A High Court judge ruled that the Department of Health was responsible for the plight of eight victims whose childhood treatment straddled a previous compensation cut-off date of July 1, 1977.

The families lost children, husbands and wives who had been given injections during the 1970s at the height of the programme, which ran from 1959 until 1985.

Mr Justice Morland said that those responsible for producing the hormone - from the pituitary gland of human corpses - knew, or should have known, of the risks of CJD infection.

If doctors responsible for the treatment had been told of the risk in 1977, when the dangers were first suspected, they would have stopped the treatment, he said. They were not told until 1985, when the first deaths from CJD occurred in Britain and America.

The eight cases are in addition to 12 in which the Health Department has conceded liability during the past two years after a 1996 High Court judgment in which it was found negligent.

They involved patients whose treatment began after July 1, 1977. So far the department has paid #600,000 in compensation. Another five cases have yet to be determined but most are expected to benefit from yesterday's ruling.

An estimated 960,000 pituitaries were gathered from bodies undergoing post-mortem examinations in hospitals, and the hormone given to nearly 2,000 children with stunted growth. Some 25 people who were treated have died and another two are seriously ill from CJD, none of them related to the BSE scare in cattle.

Parents of those who died welcomed the judgment but expressed their disillusionment with the NHS, the "callous and indifferent" attitude of the authorities and the lack of political backing for their fight for justice.

Don Hefferon, 69, from Paddington, West London, said: "I think that payment should be automatically extended to all families that have been visited by this catastrophe."

His son, Saul, died at the age of 20 from CJD in 1988 after being treated between the ages of 7 and 17.

"I feel more distressed than angry or bitter," Mr Hefferon said. "I had always presumed the NHS was there to really care for people who are in extreme distress, whatever their particular illness."

His son first became sick while an A-level student planning to read history and English literature at Anglia Polytechnic in Chelmsford, Essex. His family attributed his condition to "the average young man's lifestyle of late nights, going to discos and drinking cider in the union bar". But then he gave up an art course, announcing that he could not draw any more because his hand shook.

Maureen Newman, 48, from Coulsdon, Surrey, whose son, Terence, died in 1990 aged 21 after treatment between the ages of 6 and 18, said: "I am very pleased with the judgment but just wish that we had not had to go to court. Now we have won, we can finally let Terry rest."

Compensation, which in previous cases has ranged from #90,000 to #140,000 for each family, will be settled next month, when lawyers for the eight families will meet Health Department officials to apply the judgment. David Body, their solicitor, said after the case: "After the Department of Health was found negligent in 1996, our suggestion that all remaining cases be compensated was fought at every step.

"These families were fighting a Government that refused a public inquiry and so had to seek their justice at court.

"They needed the backing of legal aid to do this. Without it they would not have been equipped to fight the bureaucracy and inertia of an enormous government department with huge resources which fought tooth and nail."

In July 1996, Mr Justice Morland ruled that the Health Department was negligent in not heeding the warning of Alan Dickinson, who in 1977 told the Medical Research Council about the risk of contracting CJD from the hormone treatment.

The judge said that the department should not have allowed any more patients to be treated after July 1, 1977, and that the families of those whose treatment began after then could seek compensation. He has now added those whose treatment straddled the cut-off date.

Yesterday's judgment does not mean the end of litigation over CJD hormone growth. In another hearing by Mr Justice Morland, expected in July, he will rule in test cases brought by six people who received the treatment as children and who live in fear of contracting the disease.

A spokesman for the Health Department said: "We accept the findings of the court in respect of liability for patients whose treatment straddled the date July 1, 1977, when negligence was found to have started, and we will apply those findings to those, if any, who may contract CJD in the future. We will be discussing the amounts of compensation with solicitors for the plaintiffs."

Inspection Process Is Dangerous, AFGE Warns Congress

American Federation of Government Employees, May 20, 1998 PRNewswire 
WASHINGTON -- Emphasizing that inspectors must continue to be the watchdogs for America's consumers -- not profit-driven processing plants -- the American Federation of Government Employees (AFGE) is urging Congress to continue the examination of all meat and poultry carcasses by the U.S. Department of Agriculture (USDA).

"The meat and poultry industry should assume more responsibility for ensuring food safety, but not at the cost of eliminating vital on-site inspections by qualified government inspectors," AFGE National President Bobby L. Harnage stressed in his statement May 20 before the House Agriculture Subcommittee on Livestock, Dairy and Poultry.

"The new inspection tasks undertaken as part of the implementation of the Hazard Analysis Critical Control Point Systems (HACCP) involve the mere review of company paperwork, rather than the direct inspection of production, equipment or facilities," Harnage continued. "While HACCP could be used to augment food safety, USDA is using it as a back door to deregulate the meat and poultry industry."

Not willing to sit back and watch while USDA abdicates its responsibility to the public, AFGE has filed suit in the U.S. District Court for the District of Columbia to halt implementation of HACCP which unwisely eliminates the critical postmortem inspection of meat and poultry carcasses and instead relies on an industry "honor system."

Harnage urged the subcommittee to hold additional hearings to allow federal inspectors and the unions that represent them to weigh in on this critical issue. "More questions need to be answered," Harnage concluded. "For instance, will USDA or the industry under HACCP determine what tasks are performed by federal inspectors and will current pilot projects include testing for such dangerous illnesses as 'Mad Cow' disease?"

The American Federation of Government Employees, AFL-CIO, is the largest union for government employees, representing 600,000 federal workers in the United States and overseas, as well as employees of the District of Columbia. AFGE represents some 6,300 federal meat and poultry inspectors nationwide.

Singeltary family experience with CJD

Listserve 22 May 98
Hello, my name is Terry S. Singeltary Sr. and on 12-14-97 my mother died of heidenhan variant CJD, she died a very hidious death. Next, on 12-14-96 exactly one year earlier,my neighbors' mother died from C.J.D. Ii have autopsies to confirm both cases.not to long after my mother had passed away,my neighbor called me and said that I needed to see something. He had been going through a box that he had come across of his mothers. Inside was a bottle of nutritional supplements called IPLEX; INGREDIANTS;VACUUM DRIED BOVINE BRAIN,BONE MEAL,BOVINE EYE,VEAL BONE,BOVINE LIVER POWDER,BOVINE ADRENAL,VACUUM DRIED BOVINE KIDNEY,AND VACUUM DRIED PORCINE STOMACH, it's a cow in a pill.

Now this woman taking these pills,died of C.J.D.there was a big article in the Galveston Daily News about all of this. I called the Texas Dept. Of Health and they came and got the pills the next day. Julie Rawlings at the texas dept. of health told me last week that the manufacturer has clammed up on them and will not cooperate anymore. They are referring all matters to their lawyers can this be? Why doesn't the federal government intervEne?

Since the story came out in the galv. news on april 27,1998.a girl called me and told me of her father dying in late 94 or early 95 of C.J.D. in galveston. She told me that my mothers doctor was also her fathers my mothers doctor would always mention the OTHER CASE but that's as far as it went.NOW i know why,her father was a BUTCHER AT A MEAT MARKET IN GALVESTON UNTIL HE RETIRED.

Makes me wonder? Did mom ever eat any beef that had come from that meat market in the last 30 or 40 years? MADCOW is here and you can call it whatever you want to. I saw it, my mother died from it. At times she would jerk so bad it would take 3 of us to hold her down.10 weeks start to finish,and she was gone.this disease that they claim is a different disease in younger folks (nvcjd) is the same damn thing. Just because it last longer and the plaques are a little more extreme,could it not be just a more extreme case of C.J.D. any young person with any disease will last longer than a older person with the same disease, because their body and organs are much younger and healthier.

The manufacturer of IPLEX is Standard Process Inc., Palmyra, Wisconsin.1-800-558-8740. I hope you find some interest in this.if you need more details,please don't hesitate to contact me."

With thanks,
Terry S. Singeltary

Texas cluster web site

21 May 98
Mark V. Gregg  
512-458-7677  fax 512-458-7616
Director, Public Health 
Professional Education
Texas Department of Health
1100 West 49th Street T-803
Austin, Texas 78756
"We've developed a CJD Web page here at the Texas Department of Health. In addition to some general information, the page links to the CDC's CJD page as well as a 1996 issue of our biweekly morbidity and mortality newsletter, the Disease Prevention News, which is also available on the Web.

Our Infectious Disease Epidemiology and Surveillance (IDEAS) Division is currently investigating what we believe to be a cluster of CJD in a small area in East Texas. The Division's number is on the Web page if you wanted to follow up with specifics."

Bansemer family web page

Jason Bansemer
South Australia, Australia
"I am the author of an Australian homepage on CJD that will be fully operational from the 13th May 1998. My mother has contracted the disease after receiving human growth hormones for fertility 26 years ago and as a result bore me. Our family has created a page about CJD at the following address and would like to request that you contain a link to us please."

Dutch patients injected with recalled blood product

May 16/98 AP
AMSTERDAM, Netherlands -- Dutch television was cited as reporting today that up to 350 patients have been injected with a blood product made with plasma from a British donor who later died of what this story describes as a disorder linked to mad cow disease, That product, Amerscan Pulmonate II, is injected into patients requiring a lung scan and enables doctors using special equipment to get an image of the lungs.

Although it was announced in Britain last year that some plasma used to manufacture the product came from a donor who died of Creutzfeld-Jakob disease, the Dutch cases were not reported until now.

The British manufacturer, Nycomed Amersham PLC, said at the time it had recalled batches of the product. The story adds that there is no evidence CJD has been transmitted by blood products, but Dutch doctors were only later informed of the donor's background.

Doctors have not informed their patients of the affected blood because they didn't want to alarm them, according to a news release from the Dutch television program Ongoing Business. The program is to be broadcast Sunday.

Earlier this year, the Hong Kong government disclosed that more than 100 patients in the city were given Amerscan Pulmonate II that may have been contaminated with CJD.

BSE in groundwater

Listserve 21 May 98
A paper by Gale P, Young R, Stanfield G and Oakes D, "Development of a risk assessment for BSE in the aquatic environment" is published in the Journal of Applied Microbiology, 1998, Vol 84, 467-477.

The summary notes the resistance of BSE prions to degradation, and states that levels of disinfection used for drinking water treatment would have little effect. The summary continues

"This paper presents the assumptions which were used to model the risks from a rendering plant disposing of cull cattle carcasses in the catchment of a chalk aquifer which is used for drinking water abstraction. The risk assessment approach focused on identifying the hydrogeological and physical barriers which would contribute to o preventing BSE infectivity gaining entry to the aquifer. These barriers include inactivation of BSE agent by the rendering process, removal from the effluent by treatment at the plant, filtration and adsorption in the clay and chalk, and dilution in the ground water.

The importance in environmental risk assessment of the cow-to-man species barrier is considered.

Two key conclusions about the environmental behaviour of the BSE agent are that prion proteins are 'sticky' and bind to particulates, and that the millions of BSE prion molecules comprising a human oral LD50 are subject to some degree of dispersion and hence dilution in the environment. Assuming that the rendering plant processes 2000 cull cattle carcasses per week, the risks to drinking water consumers were estimated to be remote. Indeed, even using worst cases assumptions an individual would have to consume 2 litres per day of tap water for 45 million years to have a 50% chance of infection through drinking water drawn from the aquifer".

Under the heading " 5.1 BSE will be bound to particulates and suspended solids in the aquatic environment" they write

"Infectivity is associated with biological membranes and infectious prion particles are insoluble (Prusiner 1991). This is responsible for many of the difficulties which have been encountered during attempts to purify and characterize the infectious agent in scrapie. Indeed, infectivity is sometimes described as 'sticky'..

The reason for this 'stickiness' and the insolubility of PrPsc are explained by the biochemistry and biophysical properties of the PrPsc molecule and, in particular, its hydrophobicity. The Prpsc molecule is amphipathic (Meyer at al 1986). This means that both hydrophilic (water-loving) and hydrophobic (water-hating) regions exist on each and every PrPsc molecule. Its amphipathic properties account for both its binding to cellular membranes and its aggregation into rods (Meyer et al 1986).

In view of their hydrophobic moieties, molecules such as prions cannot exist fee in water. Indeed, through the maximization of hydrophobic interactions, amphipathic molecules attach with great tenacity to other molecules to the exclusion of water. It is therefore believed that any BSE agent in the aquatic environment will be bound to solids and particles. In whole cattle carcasses and rendered cattle carcasses, those solids and particles to which PrPbse attaches will be proteinaceous and carbohydrate in nature.

Through decay of those components in the aquatic environment, the bound proteins will be released and hence dispersed (molecular dispersion) immediately attaching to other particles. Thus prions will be subject to progressive dispersion and dilution while remaining bound to particulates at all times."

Prusiner S B (1991) "Molecular biology of prion diseases", Science, Vol 252, 1515-1522.

Meyer R K et al, "Separation and properties of cellular and scrapie proteins", Proc. National Academy of Sciences, USA, Vol 83, 2310-2314.

Tobacco firm had secret army of scientists in smoke battle

[Commentary: this revelation has serious implications for all public health issues affecting large industries -- webmaster]

THE tobacco company Philip Morris recruited a covert army of scientists to contribute to The Lancet and other journals to counter bad publicity about passive smoking, it was claimed last night. A company "consultant" also advised a a Commons select committee on pollution.

The infiltration exercise, codenamed "Project Whitecoat", is described in a 1990 memorandum from an American law firm acting for the company, which has released some 39,000 papers as part of a Minnesota lawsuit.

The documents, published on the Internet by an American congressional committee chairman, also claim that the company established its own "learned society" in Geneva which published papers suggesting that factors other than tobacco smoke might be behind lung disease.

Under the heading "Lancet", the memo says that "one of our consultants is an editor of this very influential British medical journal and is continuing to publish numerous reviews, editorials and commitments on environmental tobacco smoke". The document does not name the person.

Richard Horton, the present Editor, did not work for the journal at the time and says that he has no knowledge of any involvement. His deputy, David Sharpe, also said that neither he nor the other two editors working for The Lancet in 1990 had any contacts with Philip Morris or the law firm, Covington and Burling.

In a commentary to be published in this week's issue, Mr Horton says that the charge made against the journal is a serious one, and surprising since The Lancet's coverage of smoking issues at the time emphasised the adverse effects, including those of passive smoking.

In the memo, consultants are defined as people "who are not paid unless they actually perform work". One document names the late Dr Roger Perry, an environmental scientist at Imperial College, London, as such a consultant. He served as an adviser to the Commons Environment Select Committee, which published a report on indoor pollution in 1991, but he is said to have told members that he had done work for the tobacco industry.

Another of the papers shows that representatives of Philip Morris and other tobacco companies met in London in 1988 to discuss how to counter bad publicity about passive smoking. One strategy suggested was to recruit scientists without obvious connections to the industry to write articles and attend conferences.

Another was to establish Indoor Air International, described by the law firm as "the world's only learned society addressing questions of indoor air quality".

Dr Helmut Gaish, who was Director of Science at Philip Morris Europe at the time, wrote: "No other resource gives the industry any similar access to the scientific community, government, and those who make decisions about indoor air quality issues and standards."

Clive Bates, the director of ASH (Action on Smoking and Health) said last night: "Philip Morris's claimed infiltration of science is a scandal. The documents clearly show the industry inventing and orchestrating controversies by buying up scientists and creating influential outlets for tainted science."

Flupirtine: future CJD drug?

Pharmacological intervention in age-associated brain disorders by 
flupirtine - Alzheimers and prion-diseases
Mechanisms of Ageing and Development 1998; 101(N1-2): 1-19
Perovic,S.; Bohm,M.; Meesters,E.; Meinhardt,A.; Pergande,G.; Muller,W.E.G.
Alzheimer's disease, a major form of dementia in the elderly has become an increasingly important health problem in developed countries. In vitro studies on primary neurons demonstrate that Flupirtine (Katadolon(R)) at a concentration of 1 mu g/ml, significantly reduces the neurotoxic (apoptotic) effect displayed by A beta 25-35, a segment of the amyloid beta-protein precursor the etiologic agent of Alzheimer's disease.

Flupirtine, which has been in clinical use since 10 years ago, prevents the toxic effect of PrP, the presumed etiologic agent of the Creutzfeldt-Jakob disease as well as the excitatory amino acid glutamate on cortical neurons. Flupirtine displays a bimodal activity. Its strongest cytoprotective effect against glutamate-induced neurotoxicity was measured if administered at least 120 min prior to the addition of the glutamate. A likewise potent anti-apoptotic activity was measured if cells were simultaneously incubated with Flupirtine and the apoptotic inducers. Administration of Flupirtine during postincubation time in the experiments with glutamate did not result in neuroprotection. In parallel with the determination of the effect of Flupirtine on the toxin (A beta, PrP or glutamate)- induced neuronal death the effect of the drug on the intracellular Ca2+ level [Ca2+](i), was measured.

It is well established that incubation of neurons with glutamate causes an increase in [Ca2+](i). It was found that a simultaneous administration of Flupirtine and glutamate did not reduce the glutamate-induced high Ca2+ level. Only if the cells had been preincubated for approximate to 30 min with the drug the intracellular Ca2+ level was significantly lower. Experimental evidence given here shows that the molecular basis for the antiapoptotic effect of Flupirtine against glutamate, triggered during pre-incubation, is an increased expression of the protooncogene bcl-2.

The neuroprotective effect determined during coincubation with the inducer is attributed to a normalization of the glutathione level which dropped in the presence of the inducers. It is concluded that Flupirtine is a promising drug to treat neurodegenerative disorders occurring with age, e.g. Alzheimer's disease and prion based diseases, like Creutzfeldt-Jakob disease. This conclusion is corroborated by the favourable pharmacokinetic profile of Flupirtine.

Effect of flupirtine on Bcl-2 and glutathione level in neuronal cells treated in vitro with the prion protein fragment

Exp Neurol 1997 Oct;147(2):518-524 
Perovic S, Schroder HC, Pergande G, Ushijima H, Muller WE

Flupirtine, trade name Katadolon, is a centrally acting nonopioid analgesic that has recently been found to display cytoprotective activity in vitro and in vivo on neurons induced to undergo apoptosis. This report shows that the PrP106-126 fragment of the prion protein, which is the likely etiological agent for a series of encephalopathies, is toxic to cortical neurons in vitro. Simultaneously, PrP106-126 influences the molecular GSH content and the bcl-2 expression in neurons. Significant toxicity (32% reduction in cell viability) was observed at a concentration of 50 microM of the peptide after 9 days of incubation, while at higher concentrations toxicity increased to 70%. Neurotoxicity was greatly reduced following coincubation with 1 to 3 microg/ml flupirtine. Concomitant with PrP106-126-mediated cytotoxicity, glutathione (GSH) content fell by > 70% with respect to untreated controls. This decrease in GSH level was strongly blocked by flupirtine under incubation conditions that reduce cell toxicity. In addition to normalizing GSH content, flupirtine induced the expression of the anti-apoptotically acting proto-oncogene bcl-2.

Based on these in vitro data and on the favorable pharmacokinetic profile of the drug, we strongly suggest that flupirtine may prove useful for treatment of patients with prion disease.

Recombinant factor VIII may not abolish risk of new variant CJD from factor VIII

BMJ 1998;316:1385 ( 2 May ) Letters
J P Betts, International technical affairs director.   Grupo Grifols, Cambridge CB4 4GP
Barbara and Flanagan report the precautionary measures against new variant Creutzfeldt-Jakob disease that have been announced by the UK Department of Health.1 Unfortunately, the secretary of state announced the outcome of the NHS review of the provision of factor VIII for patients with haemophilia at the same time. The rationale for endorsing the use of recombinant factor VIII in children has thus become linked to concerns over new variant Creutzfeldt-Jakob.

Recombinant factor VIII is a biologically derived product produced by cell culture, not a synthetic product as stated in the announcement from the Department of Health. This is an important distinction because the word synthetic may be taken to imply that recombinant products do not carry a risk of transmitting infectious agents.

Recombinant factor VIII typically has a total protein content that is greater than or equivalent to that contained in some high purity plasma-derived factor VIII. This protein has the potential to be a source of infectiona recognised problem for all recombinant products.2 Seroconversion for virus has been reported in haemophilic patients receiving recombinant factor VIII.3 All currently available recombinant and most commercial plasma-derived factor VIII products contain human plasma protein (often as stabiliser) obtained from donors in the United States. To date, new variant Creutzfeldt-Jakob has not occurred in this population. It is therefore difficult to differentiate between recombinant factor VIII and factor VIII derived from US plasma in terms of the risk of transmission of the disease from human protein. The risk is different, however, when the content of other animal protein is considered. The final product specifications for recombinant products restrict the amout of hamster, murine, and (in one case) bovine protein as well as potentially oncogenic DNA residues. The presence of these contaminants may carry its own risk.

There is strong concern that the aetiological agent of transmissible spongiform encephalopathies can jump between animal species.4 Transmission of contamination from animal-derived starting materials is possible. Fragments of retrovirus-like particles, presumably derived from hamster culture cells, have been detected in one recombinant factor VIII.5 Finally, the complexity of the manufacturing process for recombinant products has periodically interfered with their availability, and total reliance on them may be inappropriate for many patients.

The statement from the Department of Health is misleading, and the advice given to clinicians regarding prescribing of such products is suspect in the context of new variant Creutzfeldt-Jakob disease. Yet again, political expediency has precipitated the reaction to this threat, this time to appease vocal and perhaps misinformed groups calling for recombinant factor VIII products.

*J P Betts works for Grupo Grifols, a Spanish company producing a range of products from plasma fractionation, including factor VIII, albumin, and immunoglobulins. One of the group's other companies manufactures a recombinant blood product.

1. Barbara J, Flanagan P. Blood transfusion risk: protecting against the unknown. BMJ 1998; 316: 717-718[Full Text]. (7 March.)

2. Committee on Proprietary Medicinal Products. Note for guidance: production and quality control of medicinal products derived by recombinant DNA technology. Brussels: CPMP , 1994(III/3477/92; revision 1994.)

3. Aygoren-Pursun E, Scharrar I. A multicenter pharmacosurveillance study for the evaluation of the efficacy and safety of recombinant factor VIII in the treatment of patients with hemophilia A. Thromb Haemostas 1997; 78: 1352-1356.

4. Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, et al. Transmissions to mice indicate that `new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501.

5. Arnold D. Virus safety considerations for recombinant factor VIII (recombinant factor viii, Kogenate). Hemophilia 1995; 1(suppl 2): 22-23.

Canada to use eyelid test

May 12/98 Ontario Farmer RAY FORD
The Canadian Food Inspection Agency's acting chief of epidemiology, Dr. Ron Rogers, was cited as saying CFIA will co-operate with the USDA to evaluate the effectiveness of the eyelid technique. CFIA staff will visit the Washington research station to see the technique performed, and will study Canadian strains of scrapie to see if domestic strains can be detected with the eyelid test.

So far this year scrapie has been confirmed in seven flocks in Quebec and two in Ontario, with 3,400 sheep destroyed in a bid to control the disease. About 4,200 scrapie-infected sheep were slaughtered in Canada during 1997.

Toxins trigger Alzheimer's

May 26 1998 Times
HIGHLY toxic proteins trigger the first symptoms of Alzheimer's disease long before the characteristic patterns of brain damage appear, American researchers have discovered.

The new proteins, called amyloid beta-derived diffusible ligands, are a new form of amyloid beta protein, which accumulates in the brain of Alzheimer's patients as enormous fibres. The proteins are only a tiny fraction of the size of these fibres, but can interfere with the processes of learning and memory long before any physical damage becomes apparent, says Professor William Klein, of Northwestern University in Chicago.

The ligands may account for the loss of memory formation at the early stages of Alzheimer's disease and for the nerve cell death and profound dementia at the end stages of the disease. The research is published in Proceedings of the National Academy of Sciences.

The implications are that, if the symptoms are caught at a sufficiently early stage, they might be reversed, said Grant Krafft, another of the researchers.

French meat cancer alert

May 26 1998 BY BEN MACINTYRE  Times
A TOP environmental group yesterday called on the French Government to ban the incineration of rubbish after discovering dangerous levels of cancer-inducing dioxin in meat.

The National Centre for Independent Information on Waste said that laboratory tests had found high levels of dioxin contamination in veal, minced beef and steaks bought from five Paris supermarkets.

Burnt waste enters the food chain when it falls on pastures and is absorbed by dairy and beef herds. France has 300 rubbish-burning plants, the highest concentration in Europe.

In February, health inspectors ordered the closure of three incinerators in northern France after high levels of dioxin were found in dairy cows. Official figures, cited in the environmental report, forecast that between 1,800 and 5,200 people will die every year in France from cancer caused by dioxin. A French Environment Ministry study last month found that most French incinerators emit levels of dioxin well above the authorised limit.

Britain imports less than 100 tonnes of French beef a month, out of a total of more than 6,000 tonnes from the whole of Europe.

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