Tuesday, July 27, 2010

GERMAN - BCG - 1550 vor Christus


Als Blasenkrebs ( = Blasenkarzinom) werden allgemein von der Harnblase ausgehende bösartige Geschwülste  (bösartige Tumoren) bezeichnet. Als ursächlich für die Entstehung von Blasenkrebs gelten chronische Entzündungen (einschließlich Parasiteninfektionen), die Aufnahme bestimmter chemischer Substanzen (beispielsweise aromatische Amine und 2-Naphthylamin), Radiojodtherapie, abwehrunterdrückende Medikamente und künstliche Süßungsmittel. Behandelt wird der Harnblasenkrebs je nach Ausdehnung mit einer lokalen Chemotherapie, der Entfernung der Blase oder auch einer systemischen Chemotherapie. Die Heilungsaussichten sind bei früh entdecktem Krebsleiden gut. Bei bereits ausgedehnter Erkrankung mit dem Vorliegen von Metastasen ist keine ursächliche Heilung mehr möglich.

Bekämpfung des Tumors

Die Therapie erfolgt in unterschiedlichem Umfang mit verschiedenen Methoden, je nachdem wie fortgeschritten die Krebserkrankung bereits ist. Das Carcinoma in situ kann durch die Instillation von Bacillus Calmette-Guérin (BCG) in die Blase behandelt werden. Dabei handelt es sich um attenuierte Tuberkuloseerreger. Diese lösen eine Entzündungsreaktion in der Harnblase aus, durch welche die Tumorzellen vernichtet werden können. Die Behandlung umfasst ein bis zwei Zyklen. Dabei stellt sich bei rund zwei Dritteln der Patienten ein langfristiger Erfolg ein. Mit 3 und mehr Zyklen waren 2008 sogar 90,8% nach 3 Jahren rückfallfrei

http://www.indoindians.com/images/stories/health/img000052b.jpg
vaccin bcg lyophilise intradermique freeze dried


Das Bacillus Calmette-Guérin (BCG) wurde zu Beginn des 20. Jahrhunderts aus Rindertuberkelbazillen gewonnen und als Lebendimpfstoff gegen Tuberkulose  eingesetzt. 1959 wurde bei Mäusen mit transplantierten Tumoren erstmals ein positiver Effekt bezüglich der Rückbildung der Tumoren bei der Infektion mit BCG festgestellt. Die Infektion erhöhte die Aktivität des retikulohistiozytären Systems und die Zahl der Antikörper in den Versuchstieren.[31]

Bei der direkten Injektion in Tumoren konnte in vielen Fällen eine Rückbildung des Tumors beobachtet werden. Vielversprechend verliefen die Behandlungsversuche bei metastatisierten Melanomen, wo die systemische Gabe von BCG auch zu einer Rückbildung der Metastasen führte[84] und die Überlebensrate der so behandelten Patienten signifikant erhöht wurde.[85] In randomisierten, kontrollierten Studien konnten die positiven Resultate allerdings nicht bestätigt werden.[86][87]

1976 wurden erstmals positive Ergebnisse bei der Behandlung des oberflächlichen Blasenkrebses mit BCG veröffentlicht.(Alvaro Morales, Kanada)  Dabei wurde BCG direkt in die Harnblase injiziert (intravesikal).[89] In einer Vielzahl von klinischen Studien konnte die therapeutische Wirksamkeit bei der Behandlung von oberflächlichem Blasenkrebs – hierbei ist der Tumor auf die innere Auskleidung der Harnblase beschränkt – nachgewiesen werden.[90][91][92] Die Therapie mit BCG ist bei dieser Erkrankung der Goldstandard

Nach der Einschätzung mehrerer Autoren ist dies bis heute die erfolgreichste Krebsimmuntherapie.[96][94]  BCG ist dabei jedem Chemotherapeutikum deutlich überlegen. Die Wahrscheinlichkeit für ein Tumorrezidiv ist – im Vergleich zur intravesikalen Chemotherapie – nur halb so hoch. In über 80% der Fälle wird eine Eradikation, das heißt eine vollständige Eliminierung des Tumors, erreicht.[97]

Der genaue Wirkungsmechanismus von BCG ist noch nicht aufgeklärt. Die Blase ist ein weitgehend abgeschottetes und abgeschlossenes Organ, in dem BCG eine sehr hohe lokale Konzentration erreichen und eine komplexe lang anhaltende lokale Aktivierung des Immunsystems bewirken kann.[96] Durch die lokal Aktivierung werden verschiedene Zytokine in den Urin,[98][99] beziehungsweise an das Blasengewebe, abgegeben. Gleichzeitig infiltrieren Granulozyten und Monozyten die Blasenwand.[100][101] Dendritisch Zellen schütten TNF-? und Interleukin-12 (IL-12) aus. Die Ausschüttung dieser Zytokine aktiviert wiederum Zellen der angeborenen Immunabwehr (STIL), wodurch IL-12-Rezeptor-exprimierende NK-Zellen sich stark vermehren (proliferieren).[102]

Die wichtigsten Nebenwirkungen bei der Therapie mit BCG sind: Zystitis (Entzündung der Harnblase), Pollakisurie (häufiger Harndrang), Hämaturie (Blut im Harn) und Fieber. Bei Studien mit zusammen über 500 Patienten ist kein durch BCG bedingter Todesfall bekannt.

Die Idee das Immunsystem so zu beeinflussen, dass es in der Lage ist Neoplasien erkennen und zerstören zu können, ist schon sehr alt. Die ersten Berichte über Tumorregressionen nach Infektionskrankheiten datieren auf das Jahr 1550 vor Christus.[31] Im Papyrus Ebers war die empfohlene Behandlung von Schwellungen (Tumoren) ein Kataplasma  (eine Art Breiwickel, in dem sich ein Gemisch aus Pflanzenpulvern, Samen und anderen Arzneistoffen befand), mit anschließendem Einschnitt in den Tumor.[104] Eine solche Behandlung führt zu einer Infektion des Tumors.[105]

Die ersten immunologischen Versuche der Neuzeit führte 1777 James Nooth, Arzt des Herzog von Kent und Mitglied des Royal Collage of Surgeons, durch. Nooth implantierte sich mehrmals fremdes Tumorgewebe in kleine Einschnitte seines Armes um eine Krebsprophylaxe zu erreichen. Die Implantierung hatte lediglich Entzündungsreaktionen und leichtere Schmerzen zur Folge. Ein ähnliches Ergebnis erhielt 1808 Jean-Louis Alibert, der Leibarzt von König Ludwig XVIII., der sich von einem Kollegen Flüssigkeit einer Brustkrebspatientin injizieren ließ. Es stellte sich dabei lediglich eine Entzündungsreaktion ein.[106][107]


http://www.uroinfo.ca/images/brochure_images/english/bladder_tumour_bcg.jpg


Deutlich erfolgreicher waren dagegen die Experimente des US-Amerikaners William Coley (1862–1936), der als Pionier der Krebsimmuntherapie gilt. Coley war Arzt am Memorial Sloan-Kettering Cancer Center in New York City. Er hatte von einem Krebspatienten gehört, bei dem es zu einer vollständigen Remission nach hohem Fieber, bedingt durch ein Erysipel (Wundrose, eine bakterielle Infektion der oberen Hautschichten und Lymphwege) kam. Coley stellte fest, dass auch Robert Koch, Louis Pasteur, Paul von Bruns und Emil von Behring ähnliche Fälle nach einem Erysipel beschrieben hatten. So veröffentlichte Bruns 1888[108] zusammenfassend seine klinischen Beobachtungen über vollständige Sarkom-Rückbildungen bei spontanem oder auch künstlich herbeigeführten Erysipel.[109] 1891 injizierte Coley einem Krebspatienten – einem 40-jähriger italienischen Immigranten, der bereits zwei Operationen nach Rezidiven hinter sich und nach der Prognose nur noch wenige Wochen vor sich hatte – die Erysipel-Bakterien der Art Streptococcus pyogenes direkt in den Tumor.[110] Coley wiederholte die Injektionen über mehrere Monate und der Tumor bildete sich bei dem Patienten zurück.[111] Der Patient überlebte acht Jahre.[112][113][114][115] Später verwendete Coley eine Mischung (Coley´s Toxin) abgetöteter Bakterien der Arten Streptococcus pyogenes und Serratia marcescens[116] , zusammen mit den noch aktiven Endotoxinen, direkt in Tumoren. Bei Weichteilsarkomen erreichte Coley mit seiner Methode die beachtliche Heilungsrate von 10%.[107] Die Ansprechraten waren sehr unterschiedlich und die Nebenwirkungen beachtlich. Ab 1899 produzierte die Parke-Davis Corporation Coley´s Toxin, das die folgenden 30 Jahre eine weite Verbreitung erfuhr.[117][118] Ein wesentlicher Grund für die Verbreitung war, dass es bis 1934 die einzige systemische Krebstherapie war.[119] Mit der Entwicklung der Strahlentherapie und Fortschritten bei der Chemotherapie geriet Coley´s Toxin weitgehend in Vergessenheit.[120][105] Parke-Davis stellte 1952 die Produktion von Coley´s Toxin ein[117] und die FDA verweigerte 1962 die Anerkennung als geprüften Wirkstoff.[105] Der genaue Wirkungsmechanismus ist bis zum heutigen Tag noch ungeklärt, beruht aber sehr wahrscheinlich auf dem Auslösen einer Zytokin-Kaskade, die eine spezifische und unspezifische Immunantwort zur Folge hat.[87]
Paul Ehrlich um 1900 in seinem Frankfurter Arbeitszimmer

Paul Ehrlich formulierte als Erster 1909 die These, dass das Immunsystem Tumorzellen erkennen und beseitigen kann. Auf diese Weise würden viele Tumoren schon in einem sehr frühen Anfangsstadium eliminiert und der Körper so vor einen deutlich höheren Inzidenz an malignen Tumoren geschützt werden.[121]

    „Ich bin überzeugt, dass aberrierende Keime bei dem kolossal komplizierten Verlauf der fötalen und post-fötalen Entwicklung außerordentlich häufig vorkommen, daß sie aber glücklicherweise bei der überwiegenden Mehrzahl der Menschen vollkommen latent bleiben, dank der Schutzvorrichtungen des Organismus. Würden diese nicht bestehen, so könnte man vermuten, daß das Karzinom in einer geradezu ungeheuerlichen Frequenz auftreten würde"

http://www.cambridgeurologypartnership.co.uk/images/bladder%20TNM.gif
Der US-amerikanische Biostatistiker Raymond Pearl veröffentlichte 1929 eine Atopsiestudie, in der er eine signifikant niedrigere Krebsrate bei Patienten mit Tuberkulose feststellte.[122] Als sich im Jahr darauf das Lübecker Impfunglück mit dem Bacillus Calmette-Guérin (BCG) – einem Impfstoff gegen Tuberkulose – ereignete, bedeutete dies das vorläufige Aus für entsprechende Therapieansätze in der Onkologie. Erst gegen Ende der 1950er Jahre griff Lloyd J. Old die Idee wieder auf und führte BCG erfolgreich in die Krebsimmuntherapie ein. Ab 1969 wurde BCG dann in der klinischen Praxis eingesetzt.[94]
Frank Macfarlane Burnet 1945 in seinem Labor

Lewis Thomas (1913–1993)[123] und der spätere Nobelpreisträger Frank Macfarlane Burnet[124] griffen unabhängig voneinander Ehrlichs These in den 1950er beziehungsweise 1970er Jahren wieder auf und formulierten die Hypothese der „Immunüberwachung" (immunosurveillance) bei der Tumorentstehung.[125] Sowohl Thomas als auch Burnet vermuteten, dass die T-Zellen eine wesentliche Rolle bei der immunologischen Überwachung spielen.[126]
Eine Nacktmaus hat durch das Fehlen des Thymus ein sehr eingeschränktes Immunsystem.

Die Hypothese der Immunologischen Überwachung war lange Zeit sehr umstritten und schien durch Versuche mit Nacktmäusen in den 1970er Jahren sogar widerlegt zu sein.[127] Nacktmäuse, auch athymische Mäuse genannt, haben durch den fehlenden Thymus ein stark eingeschränktes Immunsystem. Der These der Immunüberwachung entsprechend, sollten diese Mäuse gegenüber Mäusen des Wildtyps erheblich häufiger Tumoren entwickeln. Bei vergleichenden Versuchen mit 3-Methylcholanthren – einem starken Karzinogen, das bei Mäusen Sarkome induziert – war in der Tumorrate kein signifikanter Unterschied zwischen athymischen und normalen Mäusen zu erkennen.[128] Einige Jahre später wurde allerdings festgestellt, dass Nacktmäuse entgegen den ersten Vermutungen nicht völlig frei von T-Zellen sind,[129][130] und zudem über eine normale Anzahl von NK-Zellen verfügen.[131] Speziell die NK-Zellen können von sich aus gegen Tumorzellen aktiv werden.[132]

Der definitive Beweis für die Immunüberwachung wurde 2001 durch Vijay Shankaran und Kollegen erbracht. Knockout-Mäuse, bei denen das RAG2- und das STAT1-Gen abgeschaltet wurden, hatten eine erheblich erhöhte Inzidenz zur spontanen oder chemisch induzierten Tumorbildung. Die Genprodukte von RAG2 und STAT1 spielen für die Reifung der T- und B-Zellen, beziehungsweise bei der Signalvermittlung nach Bindung an den ?-Interferon-Rezeptor, eine wichtige Rolle.[23][133][40]

http://www.hisandherhealth.com/images/stories/doctor_morales.jpg

Alvaro Morales u. a.: Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. In: The Journal of urology 116, 1976, S. 180–183 J Urol. 1976 Aug;116(2):180-3. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. Morales A, Eidinger D, Bruce AW. Abstract Patients with recurrent superficial bladder tumors have been treated by vesical and intradermal administration of Bacillus Calmette-Guerin. The pattern of recurrence in 9 patients has been altered favorably. Although the findings are still preliminary they appear to hold promise of a new therapeutic approach to the treatment of a group of neoplasms for which effective therapy is still lacking.


Bei der Therapie gegen den Blasenkrebs wird, wenn dieser "high grade Stadium" hat, nicht Mitomycin sondern BCG, solche (abgeschwächte) Tuberkelbazillen verwendet. Wissenschaftlich heißt es: Eine neuere Anwendung für BCG ist die Behandlung bestimmter Formen von Blasenkrebs. In den späten 1980er Jahren zeigte sich, dass durch Verabreichung in die Harnblase eine effektive Form der Immuntherapie dieser Krankheit bewirkte.[1] Obwohl die exakten Mechanismen noch immer unerforscht sind, bewirkt BCG hier offenbar eine lokale Immunreaktion gegen den Tumor. Etlichen Studien, meist aus den USA, kann man entnehmen, dass BCG auch mit Interferon gegen den Blasenkrebs eingesetzt wurde. Dies schon vor über 10 Jahren. Noch nicht so alt sind Untersuchungen, wo festgestellt wurde, dass BCG in der sonst üblich (hohen) Dosis nicht mehr bringt, als nur die Hälfte der Dosis. Weiters gibt es seit kurzer Zeit auch Berichte, wo BCG mit Mitomycin "vermischt" instilliert wurde.

BCG wird also für agressivere Tumore verwendet, wo Mitomycin nicht mehr so geeignet scheint.

Du kannst dir auch schon denken, dass BCG kein Aspro ist, sondern ein äußerst wirkungsvolles, aber gefährliches Medikament.

Mit der Immuntherapie BCG erreicht man, einfach gesagt, dass nach der Tumorentfernung in der Blase "Entzündungen" entstehen, die dann 
die körpereigene Immunabwehr massiv in Bewegung setzt.

Mitomycin soll bereits innerhalb von 6 Stunden das erste Mal instilliert werden, auf die Abtragungswunde, als Frühinstillation. Anschließend erfolgen die
Instillationen meist 1x wöchentlich.

BCG aber darf erst ca. 2 Wochen nach der Tumorabtragung bzw. der Transurethalen Resektion Blase (TURB) instilliert werden. Alle Wunden müssen verheilt sein, auch ggf. offene Stellen durch den Katheter.

Es gilt aber bei der BCG-Instillation, vorher und nachher, noch viel zu beachten.

  


Pfizer kills and revives ... for profit. (part 2)


www.corporatewatch.org

Pfizer Inc


Corporate Crimes


Heavily Overpricing Pharmaceuticals

Most Profitable Industry
According to the Financial Times, five of the top ten companies with the most profitable foreign operations were pharmaceutical companies (27/4/2000). According to industry apologists, the profits are justified due to the unusual nature of the business: research and development costs for new drugs require huge investments (sometimes upwards of $300 million (£204,6 million) with equally large amounts of risk that the investment will pay off. Critics however, claim that prices are kept artificially high even when the initial investment is recovered.

Huge Marketing Expenditures
A new report (released on 10 July 2001) by the consumer health organization Families USA [33] refutes the pharmaceutical industry's claim that high drug prices are needed to sustain research and development. The report documents that drug companies are spending more than twice as much on marketing, advertising, and administration than they do on research and development; that drug company profits, which are higher than all other industries, exceed research and development expenditures; and that drug companies provide lavish compensation packages for their top executives [34].

Among the nine pharmaceutical companies examined in the report (Merck, Pfizer, Bristol-Myers Squibb, Pharmacia, Abbott Laboratories, American Home Products, Eli Lilly, Schering-Plough, and Allergan) all but one (Eli Lilly) spent more than twice as much on marketing, advertising and administration than they did on research and development. Eli Lilly spent more than one and one-half times as much. Six out of the nine companies made more money in net profits than they spent on research and development last year.


(According to its 1999 annual report, Pfizer spent 39,2% of its revenues on marketing and administration. The company legitimises these huge expenditures by claiming they serve an educational function: doctors and the public learn about new and useful drugs. See also the Pfizer publication 'Economic Realities in Health Care Policies', volume 2, issue 1, 'Prescription Drug Advertising: Empowering Consumers Through Information', at: www.pfizer.com/pfizerinc/policy/ERhealthcare.pdf)

Exorbitant pay for executives
The report also documents profligate spending on compensation packages for top pharmaceutical executives. The executive with the highest compensation package in the year 2000, exclusive of unexercised stock options, was William C. Steere, Jr., Pfizer's Chairman, who made $40.2 million (£27,4 million). The executive with the highest amount of unexercised stock options was C.A. Heimbold, Jr., Bristol-Myers Squibb's Chairman and CEO, who held $227.9 million (£155,4 million) in unexercised stock options. [See charts 2 and 3]

Publicly funded research
Another reason why the relationship between profits and innovation (R&D) isn't as straightforward as the industry claims is that a large part of research is publicly funded. It is a general practice that research (in any given field) starts in the public sector. Only when corporations feel that research (results) will potentially create huge profits they become interested and involved.

The top ten drug companies in the US are reported to spend on average 20% of their revenues on R&D, of which 40% is paid by the (public) National Institute of Health (NIH) [35]. A study by the Boston Globe newspaper in 1998 found the National Institutes of Health (NIH) laboratories spent $1 billion on drug and vaccine development in the 1996 tax year, but only took $27m in royalties.

In September 1999, it was pointed out to the director of the NIH, Harold Varmus, that six HIV/Aids drugs, as well as anti-malarial treatments and other medicines of vital interest to developing countries, had been invented with public funds. The government therefore had the right under US law to use the drugs in public health initiatives.

Dr Varmus dismissed the suggestion, echoing the industry line that: "Undermining licensed intellectual property rights would, I believe, unnecessarily jeopardise the development of important therapeutic drugs." James Love, who runs a Washington-based group called the Consumer Project on Technology, sees the response as nonsensical because it was the NIH which did the hard work of discovering and synthesising the drugs in question.'[36]

(James Loves blames both the US government and the US public. He elaborates on the absurd situation by saying: 'The rest of the world will have to go however many years more of paying an astronomical sum for something invented by the United States government. How can we expect Glaxo SmithKline to share its intellectual property if the United States government won't share its intellectual property to save millions of people? What does that say about the moral character of the American public? We are responsible.')[37]

Creative Accounting
The Guardian reports that drug companies try to make their R&D budgets look bigger by means of creative accounting. 'With a little creative accounting, all manners of expenditures have been logged under the R&D title, partly in the pursuit of tax rebates.'[38]

Protecting Profits through Patents
The US government tries to enforce strict patent laws all over the world. These Intellectual Property Rights (IPRs) that protect newly invented drugs (up to 20 years), enforced by the World Trade Organisation, are preventing access to essential medicines by the developing world. And patent protection of drugs can prevent poor countries from producing cheaper local versions. In Thailand, for example, Pfizer used to be the sole supplier of fluconazole, used in treating cryptococcal meningitis, an opportunistic infection affecting 1 in 5 of the country's AIDS patients. The company charged a daily price of £8.75 ($14), making the drug largely unaffordable. The market exclusivity on the drug expired in 1998, leading to its local production at 5% of the 1998 price [39].

Oxfam has recently accused Pfizer of moral bankruptcy by pricing life-saving drugs beyond the reach of millions of poor people. Oxfam particularly criticizes Pfizer's aggressive enforcement of patents in poor countries, forcing prices up. 'The company's bottom line seems to matter more than the lives of the world's poorest people', said Oxfam Policy Director Justin Forsyth. 'Pfizer's market value exceeds the combined national incomes of the 18 biggest countries in sub-Saharan Africa, but it heartlessly continues to lead the industry's campaign for global monopolies on life-saving drugs while people die from treatable diseases.' [40]

2000 Financials for U.S. Corporations Marketing Top 50 Drugs for Seniors
Chart 1 Percent of Revenue Allocated to:
Private Company Revenue
Net Sales
in $ millions: Profit:
(Net Income) Marketing/
Advertising/
Administration Research and
Development (R&D)
Merck and Co. Inc 40,363 17% 15% 6%
Pfizer Inc 29,574 13% 39% 15%
Bristol-Myers
Squibb Company 18,216 26% 30% 11%
Pharmacia Corporation 18,144 4% 37% 15%
Abbott Laboratories 13,746 20% 21% 10%
American Home
Products Corporation 13,263 -18% 38% 13%
Eli Lilly and Co. 10,862 28% 30% 19%
Schering-Plough
Corporation 9,815 25% 36% 14%
Allergan, Inc 1,563 14% 42% 13%

Five Highest Paid Drug Company Executives Salaries
2000 Annual Compensation Exclusive of Unexercised Stock Options
Chart 2
Private Executive Company Compensation
Executive William C. Steere, Jr., Chairman Pfizer Inc $40,191,845
William C. Steere, Jr., Chairman; John R. Stafford, Chairman and CEO American Home Products Corporation $27,008,927
Edward M. Scolnick, Executive VP Merck and Co., Inc. $26,454,600
Richard Jay Kogan, Chairman and CEO Schering-Plough Corporation $21,444,020
David W. Anstice, President, the Americas Merck and Co., Inc. $19,600,975

The Five Drug Company Executives Salaries
with the Largest Unexercised Stock Options in 2000
Chart 3
Private Executive Company Compensation
C.A. Heimbold, Jr., Chairman and CEO Bristol-Myers Squibb Company $227,869,513
Raymond V. Gilmartin Chairman, Pres., and CEO Merck and Co., Inc. $181,252,976
William C. Steere, Jr., Chairman Pfizer Inc. $130,944,439
K.E. Weg, Vice Chairman Bristol-Myers Squibb Company $84,282,547
John R. Stafford, Chairman and CEO American Home Products Corporation $81,847,569

In sum, the pharmaceuticals industry's claim that high profits (and strict patent laws, and high drug prices) are needed to secure the high costs of R&D (and 'safeguard the development of new, life-saving drugs to fight diseases like cancer and Aids') does not hold ground!

First, drug giants like Pfizer spent much more money on marketing and advertising than on R&D. Second, much money is being channeled to the Executive's bank account. Third, large part of research is publicly funded. Fourth, by way of creative accounting corporations make their R&D look bigger. Fifth, it's not true that the enormous corporate profits come from innovations (as is being claimed), it is the artificially high drug prices and strict patent laws (out-pricing drugs for poor people) that are securing the industry's profits. Finally, one should not forget about the industry's extensive influence on policymaking processes. The industry's ability to push for regulations and laws that suit their own interests is obviously highly to the industry, and yet another critical way to secure its high profits.


2. Price fixing (Pfizer labeled as Top Corporate Criminal)
Pfizer was listed as number 17 on the list of the 'Top 100 Corporate Criminals of the 1990's'. The company had been accused of participation in two international price fixing conspiracies in the food additives industry [41].

3. Pfizer cares for your health, as long as the company sees profit
'The UK National Health Service (NHS) is suffering from increasing shortages of older but crucial medicines leaving patients at risk of being deprived of the most effective treatments. The medicines involved are most often those used in hospitals. Generally they no longer make much money for the makers, and in some cases, the drug firms may be struggling to make any profit on them.'[42]

4. Pfizer & Aids
Pfizer is proud to state the company has made huge donations to the National AIDS Fund since 1989 [43]. After all --in the words of CEO McKinnell-- the HIV/Aids crisis is 'a crisis of heartbreaking proportions, especially for those of us committed to serving patients' (obviously referring to himself and the Pfizer company, but what about the HIV/Aids patients themselves? Shouldn't they be mentioned first?). McKinnell continues: 'We at Pfizer believe that the only realistic approach to solving this crisis is through partnerships. The pharmaceutical industry cannot do it alone…and the crisis can not be wished away. What we can do is build partnerships for a healthier world.'[44]

Pfizer's latest contribution to the fight against Aids involves the free distribution of Diflucan (Diflucan is not a treatment for Aids, but it is highly effective in treating 2 opportunistic infections that afflict large numbers of people with Aids) in 50 poor, HIV/Aids-affected countries. Pfizer developed this program in cooperation with the United Nations and the World Health Organization. Additionally, Pfizer and the Pfizer Foundation are providing construction and seed funding for the first large-scale HIV/Aids medical training centre in Africa.

However, it's rather grim (to put it subtly!) that at the same time, Pfizer's unscrupulous practices (e.g. heavily overpricing medicines, enforcement of strict patent laws, focus on the development of drugs for the rich, western consumers (the bulk of research and investments is going to so-called 'lifestyle' drugs for wealthier consumers), ignoring poor people's needs) take lives and cause misery on a large scale, especially in poor countries.

As mentioned above, Pfizer makes a AIDS drug called fluconazole (Diflucan). It treats a painful brain infection called Cryptococcal meningitis. Without treatment, the infection kills people with AIDS in two months. About 10% of the 34 million people with HIV worldwide will develop this brain infection. Pfizer's fluconazole brings in more than one billion dollars in sales each year. Around the world poor people with AIDS suffer and die without this drug, because Pfizer's price gouging keeps it out of reach of the countless people who need it.

In South Africa, where 4.5 million people have HIV, no one can afford Pfizer's killer prices. AIDS activists in South Africa and the United States have been demanding that Pfizer drop the price or allow generic production of the drug. Instead, Pfizer opposes efforts by foreign companies to make and sell the same or similar medicines at considerably lower prices. In South Africa, Pfizer's patent means that even the government must pay $4.15 (£2,83) per pill, while in Thailand, where Pfizer does not have a patent on fluconazole, the drug is only $0.29 (£0,19) per pill. In Kenya, where Pfizer also has exclusive rights, fluconazole costs $18.00 (£12,28) per pill -- more expensive, even, than US prices.

While Pfizer blocks access to affordable, generic fluconazole, countless numbers of people with AIDS die preventable deaths. In an unprecedented resolution, the United Nations Subcommission for the Protection and Promotion of Human Rights recently found that the WTO's rules on pharmaceutical patents are anathema to human rights, and will effectively cripple efforts by developing countries to deal with epidemics of disease. The resolution states that there are "apparent conflicts between the intellectual property rights regime embodied in the (WTO rules), on the one hand, and international human rights law, on the other."[45]

Pfizer keeps insisting that strict patent rules are needed to stimulate innovation. 'Patent protection makes drug discovery possible and profitable. It is the incentive that justifies investing billions of dollars and decades of time to find new cures. Eliminate patent protection, and the incentive for original research is removed and every research-based pharmaceutical company becomes a generic drug manufacturer, and the discovery of new medicines slows to a trickle.' [46] As pointed out earlier, this reasoning is based on nothing but false grounds.

Every time high-level, international meetings on health or drug-related issues come up, NGOs, activists and other concerned people seek extra attention for the pharmaceutical industry's irresponsible and unscrupulous attitude towards the Aids crisis. At the same time, drug companies –being in the spotlight- take advantage of the opportunity to work on their image. Just before the AIDS2000 conference in Durban, Pfizer announced the company would donate fluconazole (Diflucan) free of charge to people with HIV/Aids.

The Treatment Action Campaign (TAC) supported the donation. However, TAC was soon to find out that the Pfizer still considered profits more important than people's lives. It seemed the donation was highly limited, and could not be considered something else than a fraud to protect the company's profit. Pfizer insisted on limiting its donation to a period of two and a half years -the exact period when their fluconazole patent or exclusive licence to sell will expire. Second, Pfizer refused to extend the offer to treat thrush (see TAC leaflet). Third, Pfizer refused to include countries other than South Africa in the offer. And finally, Pfizer refused to reduce the price to lower than R4.00 per capsule for all other uses. On top of that, Pfizer's unwillingness to negotiate is condemning countless people to suffering and possible death because they cannot afford the unreasonable price that the company is putting on the drug [47].

More recently, as mentioned earlier, Pfizer has announced that it will offer Diflucan at no charge to HIV/Aids patients in 50 poor countries where HIV/Aids is prevalent. No dollar or time limit this time. The Diflucan Partnership was developed in cooperation with the United Nations and the World Health Organization and expands on the aforementioned partnership with South Africa. The announcement came just weeks before the UN's special session on HIV/Aids in June 2001. However, and this cannot be overstated, donations are meaningless as long as drug companies like Pfizer keep overpricing their drugs and enforcing strict patent laws.

Pfizer's statement that the company supports donation programs 'because medicines are unaffordable for many patients in the least developed countries' is highly misleading. It is the practices of drug giants like Pfizer (see above) that cause this scandalous situation! The following paragraphs on the broadly publicised lawsuit (pharmaceutical industry vs. the South African government) clearly illustrate this.

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5. Lawsuit South Africa
For more than three years, the big pharmaceutical companies have been spit-shining their image as mankind's saviors while simultaneously waging a legal battle to keep low-cost versions of lifesaving drugs from the millions of people dying of AIDS in Africa. On April 18, 2001, the 39 drug companies (including Bayer AG, Bristol-Myers Squibb, Eli Lilly Ltd, Glaxo Wellcome Ltd, Hoechst Ltd, Novartis Ltd, Novo Nordisk Ltd, Pharmacia & Upjohn Ltd, Rhone-Poulenc Ltd, Roche Ltd, Schering Ltd, Smithkline Beecham Ltd, Universal pharmaceutical, Zeneca Ltd, Merck & Co, Rhone-Poulenc Rorer SA, Warner-Lambert) suing the South African government dropped their lawsuit.

Typically, they're spinning it as a humanitarian gesture, but it really is the only way to extricate themselves from the public relations nightmare their cold-blooded effort had become. From AIDS activists who started protesting two years ago to Nelson Mandela, who this week called the law suit a "gross error ... that is completely wrong and must be condemned," the public outcry had reached a crescendo the industry could no longer afford to ignore. This, after all, is the same industry that last year spent $1.7 billion (£1,159 billion) on TV ads promoting its products and painting itself as a paragon of virtue and compassion [48].

Arianna Huffington writes: Ironically, it was not long after I had seen for the umpteenth time Pfizer's heartstring-tugging TV spot proclaiming "Life is our life's work" that I heard the drug companies were waving the bloodstained white flag in Pretoria. That it took the world turning on them -- and three long years of thousands of people dying -- to get them to drop their suit proves that the industry's collective slogan should be "Profit is our life's work."[49]

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6. Drugs = Soft Drinks
As mentioned before, Pfizer can attribute its economic success largely to its ability to turn drugs into multi-billion dollar products. The company generally spends more money on marketing than on research and development. The importance of marketing (Pfizer set the example) has rippled through the industry. It is manifested in the 'arms race' of escalating numbers of sales representatives, particularly in the US; the huge pre-launch marketing budgets when companies try to make as big a splash as possible; and the aggressive TV advertising campaigns with which some drugs, such as Claritin and Viagra, have been turned into household names.

Global launches are becoming increasingly possible as regulation between the US, Europe and Japan gradually harmonises. Companies spend increasing amounts of time and money developing a global brand name and a consistent message that can be delivered (with minor tweaks) anywhere in the world. Medicines are beginning to resemble any other consumer products. Certainly there will always be differences. New, powerful drugs will continue to be screened by trained physicians. People will never purchase chemotherapy medicines on impulse at the supermarket checkout (at least, this is what we assume…). But these days, as never before, drugs are created, branded and promoted with the consumers (note: wealthy consumers) very much in mind.

Corporations point out that the Internet and direct-to-consumer (DTC) advertising is increasing the power of patients. 'We are no longer in an age where an ill-informed patient goes to see a doctor for advice. More often than not the patient is already well informed before they go through the surgery door', says David Baker, head of European life sciences at Computer Science's Corporation, a consultancy. But an essential question is 'by whom are patients informed?' The answer is easy to find. The next important question should be 'with what intentions do drug companies provide information?' Are they genuinely concerned about people's health, or do they consider profits more important?

David Baker –reflecting the industry's vision- continues: 'Time is money. If the patient wants a product and it's indicated [licensed for that condition] and it's a good product, then why should the doctor start a discussion.' So the next step would be to leave the doctor out altogether. It seems that drug corporations like Pfizer want to remove as many links as possible between themselves and the consumer (by way of direct-to-consumer (DTC) advertising, and use of the internet) in order to enlarge opportunities to influence the consumer. It's unlikely that consumers, being dependent on the information provided by corporations and being the target of comprehensive PR and marketing efforts will find themselves in a more favourable, empowered position as the pharmaceutical industry predicts/promises.

(Further up in this profile you can find information on Pfizer's latest, ambitious marketing effort (dangerously linking propaganda/public 'education' with amusement/fun) involving the building of 12 billion dollar Business Park)

According to Cap Gemini, a consultancy, direct-to-consumer advertising now accounts for 16 per cent of total promotional spending in the healthcare industry. In terms of TV advertising, medicines come third after cars and retail products. Such advertising is largely a US phenomenon following a relaxation in regulations in 1997, a change currently under review. But in Europe, where direct advertising of branded prescription products is banned, companies have not given up the chance of creating consumer pull. They do so through Internet sites, which can be viewed from anywhere in the world. (Warnings that information is intended for US audiences only tend to be in small type.) They also promote the use of their medicines through disease awareness campaigns, such as that of Pharmacia in the UK urging patients to seek treatment for urinary incontinence. Obviously Pharmacia has the leading medicine in this field.

When Mr Ebeling joined Novartis from the soft drinks industry, what struck him most were the similarities. 'The same rules of differentiating your product, making sure you promote with the right message in the right media to the right people is really the same,' he says. 'What's different is the product, which is more complicated. But the principles of marketing and sales are the same.' Among Bayer's best-selling medicines is a brand as familiar as Coke or Pepsi. The brand, of course, is aspirin, a drug that has just completed its one-hundredth anniversary [50].

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7. Pfizer steals indigenous knowledge
The profit incentive caused a sudden revival of interest in indigenous knowledge. The progression of biotechnology opens up new possibilities to exploit natural resources in the Third World. Pharmaceutical companies increasingly take genetic material and/or indigenous knowledge from the South to make fortunes from natural remedies, without asking for consent, let alone paying any kind of compensation. After patenting the 'new inventions', the Western drug industry can exploit the South even further by forcing developing countries to pay high royalties over the patented drugs imported from the West --drugs that originate from their soil and knowledge! The following case is just another sad example of this general practice, also labeled as bio-piracy.

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Pfizer has recently been accused of stealing an ingredient of the Hoodia cactus which African tribesmen have used for thousands of years to stave off hunger and thirst on long hunting trips. The Kung bushmen who live around the Kalahari desert in southern Africa used to cut off a stem of the cactus about the size of a cucumber and much it over a couple of days. According to tradition, they ate together so they brought back what they caught and did not eat while hunting. Now the Hoodia is at the centre of a bio-piracy row.

Last April, Phytopharm, a small firm in Cambridgeshire, said it had discovered a potential cure for obesity derived from an African cactus. It emerged that the company had patented P57, the appetite-suppressing ingredient in the Hoodia, hoping it would become a slimming miracle. Phytopharm's scientists boasted it would have none of the side effects of many other treatments because it was derived from a natural product. The discovery was immediately hailed by the press as a 'dieter's dream' and Phytopharm's share price rose as City traders expected rich returns from a drug which would revolutionise the £6bn market in slimming aids. Phytopharm acted quickly and sold the rights to license the drugs for $21m (£14,321m) to Pfizer.

While the drug companies were busy seducing the media, their shareholders and financiers about the wonders of their new drug, they had forgotten to tell the bushmen, whose knowledge they had used and patented. Phytopharm's excuse appears to be that it believed the tribes, which used the Hoodia cactus, were extinct. The tribesmen were angry, saying their ancient knowledge had been stolen, and planned to launch a challenge and demand compensation. Speaking to the Observer, the lawyer for the bushmen Roger Chennells said: 'They [the bushmen] are very concerned. It feels like somebody has stolen their family silver and cashed it in for a huge profit. The bushmen do not object to anybody using their knowledge to produce a medicine, but they would heave liked the drug companies to have spoken to them first and come to an agreement.' [51]
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8. Pfizer 'illegally tested drugs on children'
The Guardian reports that Pfizer has been accused of irregularities during a clinical trial in Nigeria. The company is said to have used an experimental drug on sick children during a major outbreak of meningitis, without official approval. A Nigerian doctor employed by Pfizer to run the clinical trial in Kano said that the letter certifying approval by the ethics committee at the hospital where the children were treated was probably written a year after the experiment took place. The hospital's medical director, Sadiq S Wali, talking to the Washington Post, confirmed this. He told the Post that the document was 'a lie'. He said the hospital had no ethics committee at the time of Pfizer's trial.

The revelations were hugely embarrassing to Pfizer. The company still insists there was a philanthropic element to the trial. 'Médecins Sans Frontièrs (MSF) was using the only drug that was available in Nigeria –one that had not been allowed in the west for 50 years because of the side-effects', said Pfizer's spokeswoman, Kate Robins, whereas Pfizer introduced not only its experimental drugs, but also the 'gold standard' drug used in the west. Asked why, in that case, Pfizer had treated only 200 children when the epidemic killed 15,000, she added: 'Science governs our decisions.' The experimental drugs used, Trovan, has since been licensed, but not for children. However, it is not marketed in Nigeria. Like all new drugs, which have a 20-year patent protection, the cost is too high for developing countries [52].

Obviously, the situations of drugs not allowed in the West being used in developing countries are highly immoral. Pharmaceutical companies have aggressively pushed for policies that allow for these kind of (dumping) practices to take place. In order not to let products (forbidden in the West presumably to protect the health of consumers or the environment, but more likely to prevent future damage to corporations caused by bad publicity and/or costly lawsuits) 'get wasted', corporations make sure regulations allow them to ship those products (for example, pesticides, genetic engineered foodstuffs, medicines) to the South. In addition, leverage of corporations can often guarantee that the responsible public officers, regulators or politicians temporarily close their eyes to it.

After several lawsuits in Nigeria, it was only last September that the first suit was filed in the US. The lawsuit, filed on behalf of 30 Nigerian families, alleges Pfizer violated their human rights when it set up the clinic to give Trovan to the 200 children. The families say Pfizer did not obtain "informed consent" before administering the treatment. "This test was conducted in violation of international laws and treaties," the lawsuit says, "including the Nuremberg Code of 1947, which was enacted, in part, to prevent the horrors of medical experimentation performed during the holocaust from ever happening again."

The affair is embarrassing for the world's largest pharmaceutical company, as the industry is attempting to recover from months of bad publicity over prices and access to its medicines. Aid groups say the Trovan lawsuit highlights actions even more sinister. In the developing world, some non-governmental organisations (NGOs) allege, companies are conducting sub-standard clinical trials on potentially dangerous drugs. Pfizer heralded Trovan as a medicine capable of killing bugs that had grown resistant to antibiotics. But its promise was overshadowed by safety issues, and it was never approved by US regulators for use on children [53].

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9. Pfizer sells dysfunctional heart valves
Three ex-employees of Pfizer have alleged that the company's subsidiary Shiley Inc. regularly produced artificial heart valves that workers and supervisors knew were unsafe. Their testimony confirms a Food and Drug Administration (FDA) report that claiming that the valve was manufactured under conditions 'in serious violation' of good manufacturing processes. Fractures occurred in at least 501 of the devices that were sold from 1979 to 1986, when Shiley ceased production due to 'negative publicity'. At least 250 people have died from the fractures.

Victims of the valve or their relatives name Shiley Inc. in about 200 lawsuits. At least 30 cases have been settled. The terms of the settlements, however, remain secret. Facing tens of millions of dollars in potential court awards, Pfizer has not limited itself to making settlement offers. The company is pushing for legislation that would effectively deny access to the US judicial system to foreigners injured or killed by the valve. Because over half of the recipients of the valve are foreigners, Pfizer could escape significant financial liability if the bill becomes law. However, the bill would apply to all corporations, not just Pfizer. In essence, it would shield corporations from liability for dumping their wares on an unsuspecting and already disadvantaged foreign clientele. Currently, foreign victims may bring suit in the American State courts. The Pfizer-backed bill would allow US corporations to remove almost all such cases to US federal courts [54].

The Guardian tells the story of Elaine Levenson, a Cincinnati housewife, who is waiting for her heart to explode. In 1981, surgeons implanted a mechanical valve in her heart, the Bjork-Shiley, the 'Rolls-Royce of valves', her doctor told her. What neither she nor her doctor knew was that several Bjork-Shiley valves had fractured during testing, years before her implant was done. Pfizer's offshoot Shiley Inc. never told the government. At Pfizer's factory in the Caribbean, company inspectors found inferior equipment, which made poor welds. Rather than toss out bad valves, Pfizer management ordered the defects to be ground down, which weakened the valves further, but made them look smooth and perfect. Pfizer then sold them worldwide.

When the valve's struts break, the heart contracts - and explodes. Two-thirds of the victims die, usually in minutes. In 1980, Dr Viking Bjork, whose respected name helped sell the products, wrote to Pfizer demanding corrective action. He threatened to publish cases of valve-strut failures. A panicked Pfizer executive telexed: 'ATTN PROF BJORK. WE WOULD PREFER THAT YOU DID NOT PUBLISH THE DATA RELATIVE TO STRUT FRACTURE.' He then gave his reason for holding off public exposure of the deadly valve failures: 'WE EXPECT A FEW MORE.' His expectations were realised. The fracture count has now reached 800, with 500 dead - so far. Bjork called it murder, but kept silent.

In Britain, The Guardian continues, Pfizer has little to fear. A London solicitor for the pharmaceuticals industry explains: 'US legal excesses are not visited upon defendants here.' And the drug companies want to keep it that way. If you happen to be in Blackpool today, you can drop by Pfizer's booth at the Labour Party Conference. (For more discreet approaches to Downing Street, Pfizer retains GPC Access, Derek Draper's former lobby firm.) Pfizer has two reasons to cuddle up to New Labour: it wants the National Health Service to pay a stiff price for its love potion, Viagra; and it wants to prevent a toughening of UK products liability law recently demanded by the European Union [55].

Back in the US, victims' rights are under attack. Corporate America is funding an ad campaign portraying entrepreneurs held hostage by frivolous lawsuits. But proposed remedies stink of special exemptions from justice. Eight weeks ago, the Republican senate leader slipped into patients' rights legislation a ban on all lawsuits against makers of parts for body implants, even those with deadly defects. The clause, killed by exposure, was lobbied by the Health Industries Manufacturers Association, supported by - you guessed it - Pfizer.

Now the industry seems to have won a new battle. After many debates and political tussle to define patients' rights George W. Bush managed to get a good deal, formally labelled as a 'compromise' between him and Rep. House Member Norwood, but clearly in favour of the pharma industry. The new compromise will expose health plans to more lawsuits in state courts, but will limit when patients can sue and how much they can win in damages. The question of litigation was at the core of the White House negotiations with Norwood. In essence, the compromise allows Norwood to say he is giving patients freedom to sue in state courts but includes enough restrictions [New federal law will have to spell out the exact terms under which patients can bring suits in state courts. No doubt the industry will have a major hand in the definition of these new set of federal restrictions] for Bush to say it would not promote 'frivolous lawsuits.' The compromise will be brought to the Senate any time soon [56].

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10. Heart Attack link to Arthritis Drugs

Pfizer, Merck and Pharmacia have been put on the defensive over independent scientific evidence that their billion-dollar arthritis drugs could be linked to an increase in heart attacks.

'An analysis of clinical trials by scientists from the Cleveland Clinic Foundation suggests that there is a potential increase in the rate of heart attacks, strokes and other cardiovascular events among patients on the drugs. The scientists, who report in the latest issue of the Journal of the American Medical Association, say that the data "raise a cautionary flag".'

Pharmacia and Pfizer have responded by saying: "The article . . . is not based upon any new clinical study. The companies believe it is essential to exercise extreme caution in drawing any conclusions from this type of analysis." The two companies point out that the cardiovascular effects of the drug were studied by the FDA in February [57].

(Important to note is that FDA's (= Food and Drug Authority) status is quite dubious.
The FDA is well known for its links with industry)

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11. Animal suffering
Pfizer uses animals to test its products. But of course, as a company with high stakes in animal health care, Pfizer claims to be "your pet's best friend". Pfizer gives its customers advice on 'what to do when your best friend (your pet) is hurt.' E.g., in case of osteoarthritis, when you notice the symptoms, you're being encouraged to see your veterinarian and ask him/her about Rimadyl®, a pain relief medication that can help a dog suffering from arthritis. Rimadyl is supposed to relieve pain, 'allowing for increased activity and freedom of movement, thereby improving a dog's quality of life'.[58]

But many dog-owners saw the quality of their dog's life deteriorate instead. Jean Townsend filed a class-action lawsuit was on Oct. 12 1999 on behalf herself and other dog owners whose dogs had suffered or died after taking Rimadyl® (the 'miracle drug' for arthritis heavily advertised by Pfizer). Jean Townsend's dog's situation deteriorated fast after taking Rimadyl, to the point where he had to be euthanized. Quite a few other dogs, it turned out, had suffered adverse reactions to Rimadyl as well. The class-action lawsuit alleged that Pfizer Inc. knew about the adverse side effects, and did little to communicate them to pet owners [59].

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MUST SEE FILM!!!

12. Luring doctors
Sponsoring in order to increase the company's influence, visibility and market shares is high on Pfizer's agenda. Sponsoring doctors (a general practice in the pharma industry) is considered a very effective way to bring medicines to the public. Although there is drug advertising in the lay media and many drugs are sold unofficially over the counter, the majority of drug sales come from doctors' prescriptions. Doctors are obliged to improve themselves through continued medical education (CME). Drug companies influence the content of medical education (for example, by giving false product information, by deciding on the venues, speakers, topics, and so on). They also 'seduce' doctors with gifts, sponsored meetings (including luxurious dinners, cocktail parties and comfortable overnight stays in top of the bill hotels), high payments for conducting research or publishing reports, etc [60].

Doctors are being enticed into, for example, the twisting of trial results or the groundless creation of data. A study conducted by the FDA has revealed that one in five doctors investigated, who carry out field research of new drugs, had invented the data they sent to the drug companies, and pocketed the fees. Citing case examples, Dr Braithwaite states: 'The problem is that most fraud in clinical trials is unlikely to even be detected. Most cases which do come to public attention only do so because of extraordinary carelessness by the criminal physician...'

According to Dr Judith Jones, Director of the Division of Drug Experience at the FDA, if the data obtained by a clinician proves unsatisfactory towards the drug being investigated, it is quite in order for the company to continue trials elsewhere until satisfactory results and testimonials are achieved. Unfavourable results are very rarely published and clinicians are pressured into keeping quiet about such data.

It is very easy for the drug company to arrange appropriate clinical trials by approaching a sympathetic clinician to produce the desired results that would assist the intended application of the drug. The incentive for clinical investigators to fabricate data is enormous. As much as $1000 per subject is paid by American companies, which enables some doctors to earn up to $1 million a year from drug research, and investigating clinicians know all too well that if they don't produce the desired data, the loss of future work is inevitable [61].

Thirteen of the world's leading medical journals have recently (September 2001) mounted an outspoken attack on the rich and powerful drug companies, accusing them of distorting the results of scientific research for the sake of profits. The Lancet, the New England Journal of Medicine, the Journal of the American Medical Association and other major journals accused the drug giants of using their money - or the threat of its removal - to tie up academic researchers with legal contracts so that they are unable to report freely and fairly on the results of drug trials [62].

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georpge w bush micheal moore sicko

13. Pfizer's theatre of philanthropy
In addition to the sponsorship of doctors, education, research, politicians, etc., Pfizer is keen to donate to charity. Pfizer even has a philanthropy home page and the company has set up its own charitable, 'independent' foundation, the Pfizer Foundation, Inc (www.pfizer.com/pfizerinc/philanthropy/) established by Pfizer in 1953. The Foundation's mission is 'to promote access to quality health care and education, to nurture innovation and to support the community involvement of Pfizer people'. In 2000, Pfizer Inc and the Pfizer Foundation donated more than $300 million (£204,6 million) in product and cash donations worldwide, making it, in its own words, 'one of America's most generous companies in the US.'

Given Pfizer's criminal record, and all its serious and life-threatening consequences [Most appalling is probably Pfizer's refusal to cut drug prices in poor countries and Pfizer's aggressive efforts to safeguard its patents and pricing drugs out of reach of countless people] Pfizer's donations to charity can only be labelled as a façade. Although some intentions and concerns might be sincere, and although Pfizer is (set alongside other companies) relatively generous, problems run so much deeper. And Pfizer knows it. But the fact remains that charity (preoccupation with profits and self-interest being cleverly masked up) is a good venue for brushing up the corporate image.

Besides, donations to charity are negligible in comparison to the amounts of money spent on other projects such as the 12 billion dollar business park (see below) or in comparison to Pfizer's profits. (In the first half of 2001 Pfizer's total revenue increased with 11% and equated $15.6 billion (£10,6 billion), its net income rose by 33%).[62]

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14. Twelve billion dollar Business park --PfizerWorld
On 23 April 2001 Pfizer announced that it would be building a 12 billion dollar (£8,2 billion) (!) theme park in central Florida. Funded by a consortium of Health Maintenance Organisations (HMOs) and government agencies, the park would serve as a vehicle to introduce and promote new drugs to the public. The announcement was made by the chief executive officer of Pfizer, Hank McKinnell, surrounded by such notables as chairman of HMO Kaiser Permanente David Lawrence, attorney general John Ashcroft, and vice president Dick Cheney.

Named PfizerWorld, the park will be comprised of a combination of rides, entertainment, and educational exhibits, geared at both adults and children. 'It will be a collage of information and fun,' McKinnell remarked. Ride names already proposed include The Gonococcal Caves and Heart Attack Mountain.

Also planned are a series of cute animal characters for the park, designed to excite children about science and health. With names such as Alan the Alcoholic Alligator and Diana the Diabetic Dog, each character would have a theme disease that would then serve as a bridge to information regarding a specific Pfizer product. 'What better way to educate kids about Viagra than with Mo the Impotent Mouse?' a Pfizer PR spokeswoman remarked. Pfizer has already contracted toy manufacturer Hasbro to release a series of PfizerWorld dolls and action figures to accompany the live characters.

McKinnell fended off early criticism that the park was merely an excessive advertising ploy. 'Despite what one might be thinking, this is not an extravagant corporate ploy designed to trick the easily led masses into using our overpriced drugs despite the availability of cheaper, more effective alternatives. Our only interest is in educating the public. And if Pfizer gets a little free advertising along the way, well, of course we won't complain.'

Also of some concern was the source of the 12 billion dollars needed to build PfizerWorld. One insider remarked, "Who do you think will be paying for this monstrosity? All those CEO's and politicians? No no, that money is coming right out of the public's pockets. This has to be the biggest racket this nation has seen since the JFK assassination, but all it's going to take is one look at those huggable little animals and everyone will decide that they just don't give a damn."

Despite the visible presence of the Bush administration during the announcement, government officials and politicians were surprisingly tight-lipped. 'My only comment on the issue is that both the president and I support any endeavor to teach young people about capitalism...wait...I mean about health', Cheney remarked as he was hurried into the presidential helicopter [63].

Pfizer is scheduled to break ground on the project in about two months, with an estimated completion date of Spring 2003 [64].



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15. What Pfizer doesn't tell you…

New London, Connecticut, US (2001)
Pfizer proudly told the people of New London that the company would play a big role in revitalizing New London. Pfizer had made a deal with some federal and state agencies in which Pfizer would build a global development facility on a brownfield on the bank of the river Thames. Pfizer also committed to returning a polluted, festering waterway called Bentley Creek to its original pristine condition. Not only was Pfizer going to build a 270,000-square-foot facility, but also it was to become the Pfizer Global Research and Development World Headquarters. More prestige and jobs for the people of New London…

This is what Pfizer said: 'Our Central Research group is currently developing the former New London Mills site, a 22-acre abandoned industrial property. With assistance from the State of Connecticut, the City of New London, and the New London Development Corporation, we will transform the mill site into a new Pfizer research facility, which is expected to serve as a catalyst for additional development in downtown New London. The project resulted from a successful partnering between Pfizer and numerous federal and state agencies to negotiate solutions for site contamination, wetlands, coastal area management, storm water, and other environmental issues. Because of the economic confidence that our commitment has inspired, the State of Connecticut is providing funding to rejuvenate and remediate the surrounding area, along with state and local commitments to upgrade the nearby municipal wastewater treatment facility. Besides the tangible benefits of employment and tax revenues, we believe this redevelopment will bring inspiration, innovation, and new energy that will enrich the life of New London.'

Pfizer neglects to mention the following:

# That they have received a 10 year tax abatement on their new Global Research Facility
# That the majority of employees at their new facility will not be New London residents but current Pfizer employees
# That the residents of New London may only hope to be employed in the cafeteria and janitorial sections of Pfizer
# That Pfizer has been instrumental in attempting to destroy the Fort Trumbull neighborhood. According to Claire Gaudiani, outgoing president of Connecticut College and NLDC, on whose board George Milne, Jr sits, the destruction of this neighborhood is meant to complement Pfizer's world class facility.
# That George Milne, Jr. (head of Pfizer) has committed Pfizer to 100 rooms daily in a planned hotel [65].

16. Pfizer helps out Tobacco Industry
Pfizer and Boehringer Ingelheim are about to market a new treatment for chronic obstructive pulmonary disease (COPD). COPD is a debilitating lung disease caused primarily by smoking. It kills three million people a year worldwide, is the fourth leading cause of death in the US, and the fifth-leading cause of death in the world.[66]


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References
[33] The report by Families USA is available on their web site: www.familiesusa.org
[34] www.actupny.org/reports/drugcosts.html (source: Act Up, Aids Coalition to Unleash Power, date viewed: 03/10/01)
[35] The Guardian Unlimited, February 13, 2001, 'USA: The Pharmaceutical Industry Stalks the Corridors of Power', by Julia Borger
[36] Ibidem
[37] Ibidem
[38] Lancet, British Medical Journal, 4 December 1999; 354:1893-5 www.transnationale.org/anglais/sources/sante/influence_profits__bmj_hiv.htm
(source: transnationale, date viewed: 03/10/01)
[39] Oxfam press release, 19.07.01
[40] www.oxfam.org.uk/whatnew/press/cutcost12.htm (source: Oxfam, date viewed: 04/10/01)
[41] www.corporatepredators.org/top100.html (article by Russell Mokhiber, source web site: Corporate Predators, date viewed: 04/10/01)
[42] 'Crucial medicines in short supply', by the Guardian, 15 August 2001
[43] www.aidsfund.org/pfizer.htm (source: Pfizer, date viewed:4/10/01)
[44] Pfizer's results, first half year 2001
[45] www.actupny.org/reports/pfizernyc9-00.html (source: Act Up, date viewed: 03/10/01)
[46] Pfizer Statement to Oxfam Report, 19 July 2001 (Pfizer Press Release)
See also: www.pfizer.com/pfizer/about/press/oxfamreport.html, 25/07/2001
[47] www.globaltreatmentaccess.org/content/press_releases/00/062000_TAC_PF_DP.html (TAC press release, June 2000)
[48] www.actupny.org/reports/pfizernyc9-00.html
(source: Act Up, date viewed: 03/10/01)
[49] 'The drug companies' racket' by Arianna Huffington (20/04/2001) article can be viewed at: www.salon.com/news/feature/2001/04/20/aids/ (source: salon.dom, date viewed: 04/10/01)
[50] Financial Times, http://specials.ft.com/pharmaceuticals2001/index.html
(source: Financial Times, date viewed: 03/10/01)
[51] Observer, Sunday June 17, 2001 ('In Africa the Hoodia cactus keeps men alive. Now its secret is 'stolen' to make us thin')
[52] Guardian, Wednesday January 17, 2001 ('New drug 'illegally tested on children')
[53] 'Pfizer suit adds to pressure on industry', from Financial Times, 2 September 2001
[54] www.actupny.org/reports/pfizernyc9-00.html (source: Act Up, date viewed: 03/10/01)
[55] The Guardian, 27.09.1998, 'The explosive truth behind US wave of corporate crime' by Gregory Palast (www.guardian.co.uk/Archive/Article/0,4273,3794620,00.html)
See also: Multinational Monitor, October 1991
[56] Washington Post, August 2, 2001, 'Patients' Rights Accord Reached', By Amy Goldstein and Juliet Eilperin
[57] Financial Times, 21/08/2001, http://tm0.com/sbct.cgi?s=115501900&i=380727&d=1675939, source: Financial Times, date viewed: 03/10/01)
[58] www.petnet.com/rimadyl/ (source: Pfizer, date viewed: 27/07/01)
[59] www.gooddogmagazine.com/rimadyllawsuit.htm (source: Good Dog!® News Service, date viewed: 23/07/2001)
[60] See: www.pnc.com.au/~cafmr/reviews2.html for various stories on corporate crimes in the pharmaceutical industry (source: Campaign Against Fraudulent Medical Research, CAFMR, date viewed: 03/10/01)
[61] Ibidem
[62] Pfizer's first half year results, 2001 (can be found online at: www.pfizer.com/pfizerinc/investing/midyear/2001.pdf)
[63] 'Drug firms accused of distorting research', by the Guardian, 10 September 2001
[64] New York Times, 23 April 2001
[65] http://pages.zdnet.com/orkenizer/viewsfromtheedge/id15.html (source: Views from the Edge, date viewed: 03/10/01)
[66] Pfizer's first half year results, 2001 (can be found online at: www.pfizer.com/pfizerinc/investing/midyear/2001.pdf)
 

Sunday, July 25, 2010

rare (NZ) Specialists who should know (and be interviewed)

Herbert F. Oettgen, MD

Herbert F. Oettgen
Herbert F. Oettgen, MD
I am a medical oncologist who specializes in the treatment of lung cancer and malignant melanoma. My laboratory research has identified molecular targets for vaccines and monoclonal antibodies on cancer cells. My clinical research has involved testing immunological cancer treatments including vaccines, monoclonal antibodies, and products of the immune system called cytokines.
Appointments for New Patients
866-675-5864 (866-MSK-LUNG)

Phone
212-639-7505

Education
MD, University of Cologne (Germany)

Residencies
City Hospital and University Hospital (Cologne, Germany); University Hospital (Marburg, Germany)

Fellowships
Memorial Sloan-Kettering Cancer Center

Board Certifications
Internal Medicine (Germany)

Clinical Expertise
Lung Cancer; New Cancer Treatments



http://www.sedonaobserver.com/SO_001/images/OpEdPage_Cartoon2_June05.gif

Biological agents in cancer therapy: cytokines, monoclonal antibodies and vaccines.

Oettgen HF.

Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

Abstract

Biological approaches to cancer therapy have gone through phases of early excitement and subsequent neglect and ridicule, and have now entered an era of renewed interest. Unlike Coley and his contemporaries a century ago we are using highly purified agents of impressive potency and specificity of action in our current studies. We have come a long way in dissecting their interactions in inflammation, immunity and hematopoiesis, but we have a long way to go in defining optimal conditions for their use in therapy. However one judges the promise biological agents hold for cancer therapy, it seems certain that they will be prominent subjects of future research.

PMID: 1690209 [PubMed - indexed for MEDLINE]


http://globaleconomy.foreignpolicyblogs.com/files/2009/08/health-reform-powell-editorial_cartoon33.jpg

Cancer Cell. 2010 Jul 13;18(1):9-10.

Testimony from the bedside: from Coley's toxins to targeted immunotherapy.

Park JM, Fisher DE.

Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Cutaneous Biology Research Center, Boston, MA 02114, USA.
Abstract

A new clinical study reported in the New England Journal of Medicine unveils the long-awaited outcome of anti-CTLA-4 therapy for melanoma. It provides grounds for continued enthusiasm for cancer immunotherapy, deepens our thoughts on underlying mechanisms, and suggests exciting next steps.

Expert Opin Investig Drugs. 2007 Sep;16(9):1391-403.


http://coto2.files.wordpress.com/2009/11/dependence-on-prescription-drugs.jpg


Early experience with novel immunomodulators for cancer treatment.

Thotathil Z, Jameson MB.

Ziad Thotathil

Oncologist at WDHB

New Zealand

Current
  • Oncologist at Waikato District Health Board
Past
  • Registrar at Kuwait Cancer Center
  • Registrar at kidwai memorial institute of oncology
Education
  • Royal College of Radiologists
  • National Board of Examinations
  • Bangalore University

# Thotathil Ziad; Long Jeremy
Erlotinib effective against refractory bronchorrhea from advanced non-small cell lung cancer.
# Thotathil Ziad; Jameson Michael B
Early experience with novel immunomodulators for cancer treatment.
# Thotathil Ziad S; Long Jeremy E; Kennedy Ian; Jameson Michael B; Adams Jacqui; Kuper Marion
Chemotherapy prescription patterns in colon cancer: a patterns-of-care survey in New Zealand.

Waikato Hospital, Department of Oncology, Hamilton, New Zealand.
Abstract

Immunotherapy involves the treatment of cancer by modification of the host-tumour relationship. It is now known that this relationship is quite complex and only some of the interactions have been elucidated. Early attempts at immunotherapy, such as Coley's toxins, were undertaken without an understanding of the processes mediating the effects. With a better understanding of the immunology of this anticancer response, recent trials have focussed on certain aspects of the process to stimulate an antitumour response. In this review, the authors discuss a number of novel biological response modifiers that work as general stimulants of the immune system, through varied mechanisms including induction of stimulatory cytokines (such as IFN-alpha, TNF-alpha and IL-12) and activation of T cells and the antigen-presenting dendritic cells. These compounds include Toll-like receptor agonists, several of which are in clinical trials at present. In addition to immunomodulatory activity, some compounds such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and thalidomide and its analogues also target existing or developing tumour vasculature. Some of these compounds have single-agent activity in clinical trials, while others such as DMXAA have shown promise in combination with chemotherapy without increasing toxicity. Lactoferrin is another compound that has shown clinical activity with low toxicity. At present, accepted indications for immunotherapy are limited to a few cancers such as renal cell carcinoma and melanoma. This paper looks at some of the reasons for the limited impact of immunotherapy so far and suggest possible avenues for further research with a greater likelihood of success.


http://paulclegg.typepad.com/wellness/images/2008/10/19/cancer_cure_600_4.jpg

J BUON. 2005 Jul-Sep;10(3):329-36.
The response of urological tumours to immunotherapy.

Gkialas I, Kalantzis A, Lykourinas M.

Department of Urology, General Hospital of Athens "G. Gennimatas", Athens, Greece.
Abstract

The use of immunotherapy to attempt to treat cancer is not new. At the end of the last century, William Coley observed that the tumour of a patient with a sarcoma who developed streptococcal erysipelas regressed. This led Coley to develop a collection of heat-killed bacteria, known as Coley's toxins, which he used to activate the immune system, with some reported tumour regressions. Subsequently, several investigators used BCG to treat solid tumours. When used by intralesional injection, BCG induced regressions of melanoma skin metastases in some patients, but without affecting survival. In 1976, Morales described the use of intravesical BCG to treat superficial transitional cell carcinoma (TCC) of the bladder. The efficacy of intravesical BCG remains the most successful example of cancer immunotherapy to date.

http://www.naturalnews.com/cartoons/big_pharma_church_400.gif


Iowa Orthop J. 2006;26:154-8.
The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas.

McCarthy EF.

Department of Pathology and Orthopaedic Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA. mccarthy@jhmi.edu
Abstract

In 1891, William B. Coley injected streptococcal organisms into a patient with inoperable cancer. He thought that the infection he produced would have the side effect of shrinking the malignant tumor. He was successful, and this was one of the first examples of immunotherapy. Over the next forty years, as head of the Bone Tumor Service at Memorial Hospital in New York, Coley injected more than 1000 cancer patients with bacteria or bacterial products. These products became known as Coley's Toxins. He and other doctors who used them reported excellent results, especially in bone and soft-tissue sarcomas. Despite his reported good results, Coley's Toxins came under a great deal of criticism because many doctors did not believe his results. This criticism, along with the development of radiation therapy and chemotherapy, caused Coley's Toxins to gradually disappear from use. However, the modern science of immunology has shown that Coley's principles were correct and that some cancers are sensitive to an enhanced immune system. Because research is very active in this field, William B. Coley, a bone sarcoma surgeon, deserves the title "Father of Immunotherapy".



Pharmacol Ther. 1994;64(3):529-64.
Coley's toxins, tumor necrosis factor and cancer research: a historical perspective.

Wiemann B, Starnes CO.

Department of Pharmacology, Amgen, Inc., Thousand Oaks, CA 91320-1789, USA.
Abstract

As far back as the 1700s, it was recorded that certain infectious disease processes could exert a beneficial therapeutic effect upon malignancy. Most prominent among the numerous deliberate efforts made to take advantage of these observations was that of a pioneering New York surgeon, William B. Coley, active career 1891-1936. Using a bacterial vaccine to treat primarily inoperable sarcoma. Coley accomplished a cure rate of better than 10%. This review examines the history of these efforts and presents a discussion of their corresponding relevance to present day immunotherapy.

PMID: 7724661 [PubMed - indexed for MEDLINE]


http://www.members.shaw.ca/cancerconspiracy/cartoon-clean.jpg

Nature. 1992 Nov 5;360(6399):23.
Coley's toxins.

Starnes CO.

Comment on:

    * Nature. 1992 Aug 20;358(6388):630.

PMID: 1436069 [PubMed - indexed for MEDLINE]

Nature. 1992 Aug 20;358(6388):630.
Coley's vaccine and TNF therapy.

Brouckaert PG, Fiers W, Lejeune FJ.

Comment in:

    * Nature. 1992 Nov 5;360(6399):23.

Comment on:

    * Nature. 1992 May 7;357(6373):11-2.

PMID: 1495559 [PubMed - indexed for MEDLINE]


Nature. 1992 May 7;357(6373):11-2.
Coley's toxins in perspective.

Starnes CO.

Amgen, Inc., Thousand Oaks, CA 91320-1789.

Comment in:

    * Nature. 1992 Aug 20;358(6388):630.
    * Nature. 1992 Jun 18;357(6379):545.

Abstract

Despite initial hopes, the efficacy of tumour necrosis factor in treating cancer patients has been disappointing. But a more careful selection of patients, and more appropriate treatment, might be fruitful.

PMID: 1574121 [PubMed - indexed for MEDLINE]

N Engl J Med. 1987 Aug 13;317(7):457.
A. Chekhov, M.D., and Coley's toxins.

Gresser I.

PMID: 3302707 [PubMed - indexed for MEDLINE]


http://scienceblogs.com/insolence/upload/2009/06/so_true_so_true/Null.jpg

HISTORICAL SKETCH
Coley's toxin revisited: immunotherapy or plasminogen activator therapy of cancer?
L. R. ZACHARSKI and V. P. SUKHATME*
Department of Veterans Affairs Medical Center, White River Junction, VT and the Department of Medicine, Dartmouth Medical School, Lebanon, NH, USA; and  *Beth Israel Deaconess Medical Center and the Department of Medicine, Harvard Medical School, Boston, MA, USA
Correspondence to Leo R. Zacharski, Veterans Administration Hospital, White River Junction, Vermont 05009, USA.
Tel.: 802-296-5149; fax: 802-296-6308; e-mail: leo.r.zacharski-at-dartmouth.edu
Copyright 2005 International Society on Thrombosis and Haemostasis
ABSTRACT
No Abstract

Received 11 August 2004, accepted 27 September 2004

J Pediatr. 1975 Dec;87(6 Pt 2):1094-1102.
Nonspecific enhancers of resistance in man.

Florman AL, Holzman RS.
Abstract

Nonspecific enhancers of resistance may include (1) viral interference, (2) interferon, (3) interferon inducers, (4) bacterial interference, (5) bacterial products such as Coley's "toxins," endotoxins, or staphylococcal, BCG, and Corynebacterium parvum vaccines, (6) transfer factor, and (7) well-defined chemicals such as dinitrochlorbenzene, levamisole, and vitamin C. These are discussed only as they have been applied to man to learn whether or not they have enhanced his ability to resist infections and growth of tumors. Preliminary studies suggest that a variety of relatively safe and effective nonspecific enhancers may soon be available for clinical use.

PMID: 1102645 [PubMed - indexed for MEDLINE]

Am Surg. 1969 May;35(5):377-83.
Coley's toxins and chemotherapy in treatment of breast carcinosarcoma: case report.

Chandler JJ, Crisera RV, Fletcher WS.

PMID: 5782243 [PubMed - indexed for MEDLINE]

http://bestsupplementsforwomen.com/wp-content/uploads/2010/03/Mammogram-cartoon1-282x300.jpg


Cancer. 1968 May;21(5):805-11.
Effect of Coley's toxins and irradiation on the A. melanoma no. 3 tumor in the golden hamster.

Donaldson SS, Cooper RA Jr, Fletcher WS.

PMID: 4870091 [PubMed - indexed for MEDLINE]

Acta Med Scand Suppl. 1953;276:1-103.
A review of the influence of bacterial infection and of bacterial products (Coley's toxins) on malignant tumors in man; a critical analysis of 30 inoperable cases treated by Coley's mixed toxins, in which diagnosis was confirmed by microscopic examination selected for special study.

NAUTS HC, FOWLER GA, BOGATKO FH.

PMID: 13039964 [PubMed - indexed for MEDLINE]



Saturday, July 24, 2010

german - MUSS MAN LESEN

Die Behandlung von bösartigen Erkrankungen mit aktivem Fieber

von Dr. med. Einar Göhring

erschienen in natura-med Nr. 1-2, S. 8-17 (1988)


"Fever is a mighty engine which nature brings into the world for the conquest of her enemies. " Thomas Sydenham (1629-1684)

Das Prinzip der Immunstimulierung durch aktive Hyperthermie hat bereits vorüber 100 Jahren als Methode der Erfahrungsheilkunde in die Krebstherapie Eingang gefunden. Über die Physiologie des Fiebers und die dabei ablaufenden biochemischen humoralen und zellphysiologischen Reaktionen bestehen heute klare Vorstellungen. Sie werden von den klinischen Forschungsergebnissen des Autors voll bestätigt, die ihrerseits mit dazu beitragen, der aktiven Hyperthermie als tumorwirksame Therapie mehr Gehör zu verschaffen.

Einleitung

Die Leistungen unseres Immunsystems treten für uns spürbar dann in den Vordergrund, wenn es auf Hochtouren laufen muß, um akute Infekte zu überwinden, um unseren Mitkonkurrenten in der Evolution - Bakterien und Viren insbesondere - ihre Chance zu nehmen.
Wir fühlen dann nicht so sehr die gewaltig aktivierten Mechanismen unserer Immunabwehr als die damit verbundenen unangenehmen Begleiterscheinungen: Müdigkeit, Übelkeit, Erbrechen, Appetitlosigkeit, Schüttelfrost, allgemeine und Kreislaufschwäche, oft Kopf- und Muskelschmerzen und nicht zuletzt Fieber. Wir können diese Nebenwirkungen aber besser akzeptieren, wenn wir uns klarmachen, daß unser Immunsystem dann im wahrsten Sinne des Wortes um unser Leben kämpft.
Schon oft wurde die Frage gestellt: Ist Fieber nützlich? Die Antwort scheint mir sehr einfach.
Legt man für den Fiebermechanismus das Prinzip der Natur zugrunde, damit auch den Fortbestand der Arten zu sichern, nach dem Motto, "eine Chance für jeden - aber Überleben für den Besten", so darf man den Schluß ziehen, daß dieses archaische Prinzip nicht ohne Grund auch für den Menschen erhalten wurde. Die Homöothermie, also die Konstanthaltung der Körpertemperatur beim Warmblütler, hat sich nach ihrer Einführung innerhalb der Evolution vor etwa 500 Millionen Jahren als Vorteil erwiesen. Zu einem ähnlichen Zeitpunkt, irgendwann vor 500 bis 300 Millionen Jahren, etablierten sich die Grundformen der Immunabwehr: Makrophagen im zellulären Teil und das endogene Pyrogen oder - modern - Interleukin-1 als Immunhormon, beides hervorragende Mechanismen unseres Abwehrsystems.
Aus der Chemie wissen wir, daß chemische Reaktionen bei höheren Temperaturen deutlich schneller ablaufen.
Genau von diesem Prinzip macht das Immunsystem Gebrauch, wenn es neben der Aktivierung der sog. Immunkaskade auch das System der Temperatur-Homöostase vorübergehend außer Kraft setzt. Oder richtiger: auf ein höheres Regelniveau einstellt.
Diese elegante Lösung, biochemischen Reaktionen einen Verstärkermechanismus vorzuschalten, garantiert, daß nach Infektion eine maximale Immunantwort provoziert wird, die bei der bekannten schnellen Vermehrungsfähigkeit von Erregern auch notwendig ist

Abb. 1: Der Temperatureffekt auf die Vermehrung von T-Lymphozyten


Daß diese Schnellaktivierung des Immunsystems mit einigen Kompromissen - den üblichen Krankheitserscheinungen bei einer Infektion - erkauft werden muß, sollte uns nicht zur Annahme verleiten, Fieber als offensichtliches Krankheitszeichen im Keime ersticken zu müssen: Wir nehmen damit unserer Immunabwehr die Chance, uns optimal zu helfen so, als ob man einer Feuerwehr am Brandherd das Wasser abdreht.

Geschichte der Fiebertherapie

Wie kam man nun auf die Idee, Infektionen oder das Fieberprinzip in die Krebstherapie einzuführen, wo die Zusammenhänge zwischen Immunabwehr und Krebs doch erst seit wenigen Jahrzehnten näher bekannt sind?
Anlaß waren zum einen die Beobachtungen alter Ärzte, daß Malariapatienten seltener an Krebs erkrankten, oder daß Krebskranke, zusätzlich von Malaria befallen, oftmals auch von ihrem Krebsleiden geheilt wurden. Aber auch, daß nach dem Überwinden des leichter verlaufenden Erysipels, einer Streptokokkenerkrankung, nicht selten die Krebserkrankung mit ausheilte.
Zusätzlich legen statistische Beobachtungen den Schluß nahe, daß zwischen Infektionen und Krebserkrankungen eine negative Korrelation besteht.
In der Literatur finden sich für den gezielten Einsatz des Erysipelerregers bei Malignomen erstmals Angaben bei BUSCH, dem damit 1866 die Rückbildung eines inoperablen Sarkoms bei einer 19jährigen Patientin gelang.
Mit seinem Erfolg provozierte BUSCH eine Reihe ähnlicher Versuche, die zum Teil ebenso eindrucksvoll verliefen. So konnten FEHLEISEN (1881) und BRUNS (1887) ebenfalls Tumorremissionen mit dieser ersten Form der aktiven Fiebertherapie vorweisen.
Zwischen 1870 und 1900, also schon vor mehr als einhundert Jahren, wurde das Prinzip der Immunaktivierung als Methode der Erfahrungsheilkunde in die Krebstherapie zunehmend eingeführt.
Daß hiervon häufig Gebrauch gemacht wurde, darf aufgrund einiger Doktorarbeiten angenommen werden, die sich diesem Thema in jener Zeit widmeten (u.a. VOELKER 1867, HAHN 1870, MEICHEL 1889).
Vermutlich auf diesen Erfahrungen basierend, führte COLEY die Fiebertherapie mit inaktivierten Erregern durch. Als Vakzine mit den besten Effekten stellte sich eine Mischung aus Streptococcus pyogenes und Bacterium prodigiosum (Serratia marcescens) heraus.
COLEY erzielte damit ab 1893 zum Teil aufsehenerregende Erfolge, doch konnten seine Ergebnisse mangels Standardisierbarkeit der damaligen Bakterientoxine von anderen Ärzten nicht immer nachvollzogen werden.
Unter diesen letztlich technischen Problemen litt die weitere Entwicklung der Krebstherapie mit bakteriellen Pyrogenen.
Dennoch muß man feststellen, daß die sog. "COLEY'S toxins" die älteste Therapieform mit sog. BRM-Substanzen (biological response modifiers), also immunmodulierenden Stoffen, ist und damit zugleich die älteste systemische und Immuntherapie des Krebses darstellt!

Klinische Anwendung der aktiven Fiebertherapie

Die COLEYsche Vakzine bildet auch an der ÄSKULAP-Klinik in Bad Rappenau das Prinzip der aktiven Fiebertherapie. In der Regel beginnen wir mit einer Dosierung von 1/50 Amp. (von zwei Millionen Einheiten entspr. 40.000 Keime), was der Zahl lysierter Bakterien entspricht.
Die Substanz wird intravenös appliziert. Zur Kreislaufstabilisierung geben wir noch 1/4mg Strophanthin-k, das sich bestens bewährt hat. Angestrebt wird eine Mindesttemperatur von 39 Grad Celsius (s. Temperaturverläufe bei Krebspatienten,

Abb. 2: Temperaturverläufe bei vier Karzinompatienten mit aktiver Fiebertherapie

- Tagesprofil -


Abb. 3: Temperaturverläufe bei einem Karzinompatienten mit aktiver Fiebertherapie

- Langzeitprofil -



da die Therapieergebnisse (5-Jahres-Überlebensraten) von der erreichten Temperatur abhängig sind. Hierüber hat NAUTS (1975) berichtet.


Abb. 4: Beziehung zwischen Temperatur und Überlebensraten bei der aktiven Fiebertherapie


Auf verschiedene Tumorlokalisationen nimmt diese Autorin (1982) ebenfalls Bezug .


Abb. 5: Überlebensraten von inoperablen Krebspatienten durch die aktive Fiebertherapie


Ist diese Temperatur nach drei Stunden nicht erreicht, geben wir in der Regel die gleiche Dosis nochmals.
Nach Injektionen der Pyrogene muß der Patient Bettruhe einhalten. Die Temperatur wird halbstündlich rektal gemessen und erreicht nach ein bis vier Stunden ihr Maximum. Meist geht dem ein Schüttelfrost von etwa 20-40 Minuten Dauer voraus, dabei können Übelkeit, Erbrechen, Kopf- und Muskelschmerzen, insbesondere Rückenschmerzen, auftreten. Diese lassen sich durch 1A. Pentazocin i.m. gut kupieren.
Eine Nahrungsaufnahme während des Fieberstoßes ist nicht gestattet, auch nicht sinnvoll, dies wegen der Häufigkeit von Nausea und Vomitus.
Die Flüssigkeitsaufnahme wird erst nach Erreichen des Temperaturmaximums erlaubt, da es gilt, ein zu frühes Schwitzen zu vermeiden, was zu Temperaturabfall führt. Am Abend, wenn die Temperatur praktisch ihr Ausgangsniveau erreicht hat, kann der Patient eine leichte Mahlzeit zu sich nehmen.
Im Gegensatz zur passiven Hyperthermie ist der äußere Aufwand beim Fieberstoß gering: er kann einfach im Bett durchgeführt werden.
(Bei der passiven Hyperthermie stößt man leider in der Regel an die Grenzen der Zumutbarkeit für den Patienten. Erheblich humaner - da physiologisch - verläuft grundsätzlich die aktive Fiebertherapie.)
Die Fiebertherapie ist ohne weiteres ambulant durchführbar, wie schon viele unserer Patienten und deren Hausärzte bewiesen haben, die die Nachbetreuung unserer Patienten übernahmen.
Doch ist es empfehlenswert, die ersten Fieberstöße im klinischen Rahmen durchzuführen, dies wegen der Möglichkeit zur Beurteilung, inwieweit eine Fiebertherapie auch ambulant durchführbar ist - auch, um bei Patient und Hausarzt etwaige Hemmschwellen vor der Fiebertherapie abzubauen.
Es hat sich herausgestellt, daß die Fiebertherapie sinnvollerweise bei metastasierenden Karzinomen mindestens über ein halbes Jahr fortgeführt werden sollte: Damit wurden von NAUTS (1982) die besten Überlebensraten beschrieben .

Abb. 6: Abhängigkeit der Überlebensraten von der Anwendungsdauer der aktiven Fiebertherapie

(inoperable Krebspatienten)



Die aktive Fiebertherapie wenden wir gewöhnlich einmal pro Woche an, mitunter in größeren Abständen, wenn Untergewicht vorliegt.
Bei der ambulanten Fiebertherapie hat sich ein 14-tägiger Rhythmus als günstig herausgestellt, da so auch die weitere Compliance des Patienten aufrechterhalten werden kann.
Die Dosierung der Fiebervakzine muß in vielen Fällen von Mal zu Mal erhöht werden, um eine Mindesttemperaturvon 39 Grad Celsius zu erreichen, wahrscheinlich bedingt durch die Bildung von Antikörpern gegen das Endotoxin, vielleicht auch durch physiologische Adaptionsmechanismen.
Wir setzen die Fiebertherapie bei allen Krebspatienten, vor allem auch in der Nachbehandlung, ein, da deren Immunsystem meßbar geschwächt ist, aber auch bei anderen Indikationen, soweit dies Allgemeinzustand und Organfunktionen zulassen.
Als sehr vorteilhaft hat sich auch die Kombination mit Chemotherapie erwiesen, da dies zur Verstärkung des Therapieeffektes führen kann.
Die Erfahrung zeigte, daß offensichtlich eine Potenzierung der tumorschädlichen Effekte erreicht wird (neben den eigentlichen Immuneffekten darf auch ein Verstärkermechanismus der Temperatur auf die zytostatischen Wirkungen vermutet werden).
Somit können wir bei der kombinierten Fieber-Chemotherapie auch geringere Zytostatika-Dosen anwenden:
Die Nebenwirkungen sind zum einen infolge der schwächeren Chemotherapie geringer, zum anderen ist ein zusätzlicher protektiver Effekt des aktivierten Immunsystems auf gesunde Zellen wahrscheinlich.
Vor zehn Jahren kannte man noch nicht die Immunreaktionen der aktiven Fiebertherapie im einzelnen, selbst heute sind den Datenbanken der Medizin nur wenige Arbeiten zu entnehmen, die sich mit der aktiven Fiebertherapie beschäftigen.
Eine umfassende Literaturübersicht über dieses Thema veröffentlichte NAUTS 1982.
Die immunologischen Zusammenhänge sind meist im Tierversuch beschrieben; doch unterliegt die Übertragung der Ergebnisse auf den Menschen hier nicht solchen Einschränkungen, da Immunreaktionen aufgrund der gemeinsam evolutionären Basis bei allen Warmblütern sehr ähnlich sind.

Klinische Forschungsergebnisse

Daß die seit über einhundert Jahren veröffentlichten Therapieerfolge der aktiven Fiebertherapie bei Krebs in erster Linie auf immunologischen Mechanismen basierten, war anzunehmen. Hierauf deuteten verschiedenste in-vivo- und in-vitro-Untersuchungen hin.
Auf die Identität von endogenem Pyrogen mit Interleukin-1 wies der Verfasser im letzten Jahr hin (GÖHRING 1986  siehe unten "Wie Fieber die Immunabwehr anregt"). Da Interleukin-1 an der Spitze der Immunkaskade steht, durfte angenommen werden, daß alle Folgereaktionen einer Immunaktivierung durch eine natürliche Infektion auch bei der aktiven Fiebertherapie ablaufen. Daß also der Aktivierung von Interleukin-1 eine Induktion der Vermehrung von immunwirksamen Zellen wie T4-Helferzellen oder NK-(natürlichen Killer-)Zellen ebenso nachgeschaltet ist wie die Produktion von Tumornekrosefaktor (TNF), Interleukin-2 (vormals TCGF - T-lymphocyte growth factor), Interferonen, colony stimulating factor (CSF) und anderen Immunhormonen.
Der Nachweis dieser ausgeprägten Immunstimulationen ist uns bis jetzt für alle untersuchten Immunparameter gelungen, sowohl für alle immunkompetenten Zellen


Abb. 7: Zelluläres Immunprofil bei einem Krebspatienten nach aktiver Fiebertherapie


als auch für Interleukin-1


Abb. 8: Interleukin-1-Aktivierung durch die aktive Fiebertherapie


und Interleukin-2;


Abb. 9: Interleukin-2-Induktion durch die aktive Fiebertherapie


die Überprüfung der Induktion von Tumornekrosefaktor und Interferonen ist für dieses Jahr noch vorgesehen.
Somit können wir schon jetzt die angenommenen tumorwirksamen Mechanismen der aktiven Fiebertherapie auf der Ebene der Immunaktivierung als gesichert ansehen. Hierzu sei auf die grundlegenden Mechanismen der Interleukin-1-


Abb. 10: Die Interleukin-1-Kaskade bei der aktiven Fiebertherapie


bzw. Interleukin-2-Kaskade


Abb. 11: Aktivierung der Immun-Kaskade durch die aktive Fiebertherapie


verwiesen. Diese Darstellungen erheben allerdings keinen Anspruch auf Vollständigkeit; so wurden die Rückkoppelungsmechanismen der besseren Übersichtlichkeit halber nicht eingezeichnet, außerdem ist der Wissenszuwachs auf diesem Gebiet sehr dynamisch.

Klinische Erfahrungen

Die klinischen Ergebnisse der Fiebertherapie lassen sich wie folgt zusammenfassen:
Die Ansprechrate ist bei den einzelnen Tumorarten unterschiedlich gut.
Als Tumorform mit sehr guten Remissionseffekten hat sich das metastasierende Colon-Ca. herausgestellt, wobei sich insbesondere Lebermetastasen durch die kombinierte Fieber-Chemotherapie gut bis sehr gut beeinflussen lassen. Weiterhin sprechen das Harnblasen-, Mamma- und erstaunlicherweise das Pankreas-Ca. gut an.
Bei einigen Systemerkrankungen wie M. Hodgkin und chronisch-lymphatischer Leukämie sehen wir ebenfalls gute Remissionen. Exemplarisch ist das am Fall eines Patienten (Abb. 12) dargestellt.
Die immunologische Erklärung wurde inzwischen in der Entdeckung von Differenzierungsfaktoren wie z.B. des Granulozyten-Makrophagen-Differenzierungsfaktors (GMDF) gefunden, die die Ausreifung leukämischer Zellen bewirken. Von HUTH (1957) insbesondere wurden die günstigen Effekte bakterieller Infektionen auf Leukämien beschrieben.
Auf ganz anderen Mechanismen beruht hingegen die (unphysiologische) passive Hyperthermie. Sehr einprägsam hat dies HENSEL (1981) formuliert:

"Fieber ist ein aktiver, vom Organismus selbst hervorgebrachter Vorgang, Hyperthermie ein von außen aufgezwungener Zustand. Beide sind physiologisch und pathophysiologisch grundverschieden.
Die Fieberreaktion ist ein ganzheitlicher Prozeß . .."

Einen Gesichtspunkt der aktiven Fiebertherapie kann man gar nicht genug betonen: Sie hat eine extreme therapeutische Breite. Mir sind bei nunmehr etwa 13.0001) Fieberstößen, die ich überblicke, keine ernsthaften Komplikationen bekannt, dabei sind wir in der Indikationsstellung eher großzügig.
So war unser ältester Patient 80 Jahre; Patienten mit früherem Herzinfarkt überstanden die Fiebertherapie ebenfalls problemlos.
Ich kenne kein Verfahren in der heutigen onkologischen Therapie, das einen vergleichbaren therapeutischen Index besitzt.
Wie vielleicht aus diesen Ausführungen deutlich geworden ist, stellt die aktive Fiebertherapie mit das wirksamste Verfahren dar, stärkste physiologische Reaktionen auszulösen: Die immunologischen Aktivierungen sind unübersehbar, die positiven Effekte gegen maligne Erkrankungen offensichtlich.
Nach Ablehnung durch Institutionen, die vorgeben, der Förderung biologischer Methoden der Krebsbekämpfung aufgeschlossen gegenüberzustehen (Deutsche Krebshilfe, Ausschuß für Unkonventionelle Methoden der Krebsbekämpfung, Bonn), werden wir auch weiterhin aus eigener Kraft - wenn auch in bescheidenem Rahmen - forschen und damit der aktiven Fiebertherapie ein sog. "wissenschaftliches Fundament" geben.
Abschließend möchte ich eine nachdenklich stimmende Äußerung von NAUTS (1982) zitieren:

"The fact that thousands more cancer patients were not given the benefit of such therapy since it was first initiated by Coley 90 years ago, may be one of the greatest tragedies in medical history."




Wie Fieber die Immunabwehr anregt

von Dr. med. Einar Göhring

erschienen in ÄRZTLICHE PRAXIS Nr. 32 vom 22. April 1986, Seite 1089

Fieber ist ein phylogenetisch sehr alter Mechanismus. Die Natur hat dieses Prinzip nicht ohne Grund konserviert. Immer klarer treten die fundamentalen Effekte der Fiebertherapie zutage. Immer deutlicher zeigt sich, daß Fieber einen der potentesten Immunmechanismen darstellt, der sich auch therapeutisch bei den verschiedensten Krankheitsbildern einsetzen läßt, vor allem bei onkologischen Erkrankungen.
Die aktive Fiebertherapie (im Gegensatz zur passiven Überwärmung!) rückt in der modernen Immunologie als onkologische Maßnahme besonders deutlich in den Vordergrund, seitdem erkennbar wird, welche elementaren Prinzipien der Immunantwort das Fieber zu induzieren vermag.
Es lassen sich inzwischen folgende Zusammenhänge nachweisen:
Das lange Zeit als endogenes Pyrogen (EP) bezeichnete Hormon, das bei Infekten vom Wirtsorganismus erzeugt wird, stellte sich als identisch mit einem der Lymphokine (freigesetzte Immunmodulatoren) heraus, nämlich dem Interleukin-1 (IL-1).
Dieser Wirkstoff wird heute als eine der wesentlichsten, stärksten und vielseitigsten Triggersubstanzen bei der Immunaktivierung betrachtet. Es handelt sich bei dem (alpha-, beta-)IL-1 um ein von Makrophagen, Monozyten und Keratinozyten freigesetztes Peptidhormon mit einem Molekulargewicht von 15.000 Dalton.
IL-1 steht am Anfang der sog. Lymphokin-Kaskade und stimuliert die Produktion von Interleukin-2 (IL2, früher TCGF = T-cell-growth-factor). Das ist jener Immunmodulator, der wiederum an der Aktivierung von NK-Zellen (natural-killer-ceIls) und LAK-Zellen (lymphokine-activatedkiller-cells) beteiligt ist. Gerade in letzter Zeit steht er im Mittelpunkt erheblichen Interesses der Onkologen.
Die von Endotoxinen induzierte Immunkaskade umfaßt zusätzlich noch weitere immunaktive Substanzen wie Interferone und Tumor-Nekrose-Faktor (TNF, vormals Lymphotoxin) und andere bedeutende Wirkstoffe der unspezifischen Tumorabwehr, etwa Komplement- und Properdin-Faktoren.
Die Bedeutung des Fiebers als grundlegender Mechanismus des Immunapparates wird durch den Nachweis unterstrichen, daß Endotoxine - die bei Infekten aus Bakterien oder Viren freigesetzt werden - auch durch die Fiebertherapie zur entscheidenden Immunaktivierung eingesetzt werden können. Bei einem onkologischen Patienten ist diese schicksalbestimmende Immunkette unterbrochen bzw. die Immunkaskade abgeschwächt, sei es aus genetischen oder erworbenen Gründen. Auch immunsuppressive Tumorsubstanzen können mitwirken.
Der Nachweis, daß Fieber via Interleukin-1 (endogenes Pyrogen) sowohl Interleukin-2 als auch andere Immunbotenstoffe freisetzt, wurde mittlerweile wissenschaftlich geführt und kann als gesichert gelten.
Unsere Erfahrungen mit der Fiebertherapie an der Äskulap-Klinik belegen, daß mit dieser Maßnahme zahlreiche Immunparameter in die Richtung zur Norm verändert werden können. Dazu zählt die Aktivierung von T4-(Helfer-)Lymphozyten, Reduzierung von T8-(Suppressor-)Lymphozyten, Ausgleich des B-T-Lymphozytenstatus sowie Normalisierung von Hauttest-Reaktionen zur Objektivierung der zellulären Immunantwort.
Auch wenn die Fiebertherapie in ein komplexes Therapiekonzept eingebettet ist, demonstriert die daraufhin erfolgende sichtlich beschleunigte Immunrestauration, daß der Fiebereffekt eine zentrale Rolle in der Immunstimulation und -modulation spielt.
Die immunologische Basis der Fieberwirkung ist also belegbar. Die eindrucksvollen Resultate der aktiven Fiebertherapie im ersten Drittel unseres Jahrhunderts haben so ihre Erklärung erhalten. (Mit der von Coley eingeführten bakteriellen Fiebervakzine wurden seinerzeit durchschnittlich bis zu 50 Prozent Langzeitremissionen bei histologisch gesicherten Krebs- und Sarkompatienten erzielt.)
Damit bekommt die Immuntherapie als vierte Säule der Krebstherapie das notwendige Fundament. Zugleich eröffnet sich der aktiven Fiebertherapie als einer der natürlichsten Therapiemethoden ein wichtiges Feld in der Krebsbekämpfung. Sie findet Zugang in die allgemeine Onkologie.
Nach 7.500 Anwendungen1) von komplikationsarmen Fieberstößen, die der Verfasser bis jetzt überblicken kann, wird zudem die große therapeutische Breite dieses Verfahrens ersichtlich. Bei der Würdigung der Zusammenhänge zwischen Fieber und Immunsystem wird auch klar, daß jegliche Unterdrückung von Fieber die Aktivierung der Immunkaskade verhindert oder abschwächt und damit für den Krankheitsverlauf von Nachteil sein muß.
Bereits geringes Fieber führt dagegen zur Boosterung innerhalb der Immunverstärkerkette. Literaturhinweise und eigene Beobachtungen bestätigen die beim Krebspatienten gehäuft anzutreffende Tatsache, daß er selten Fieber hat.
Wird dem Organismus die Chance genommen, auf einen äußeren Reiz mit einer ausreichenden Immunantwort zu reagieren, so nimmt man dem Immunsystem die Möglichkeit, Immunmediatoren zu bilden. Ein solchermaßen ständig supprimierter Organismus ist sicherlich nicht in der Lage, adäquat auf den immunologischen Reiz "Malignom" zu antworten.