Thursday, August 28, 2008



History of AIDS up to 1986These are some of the most important events that occurred in the history of AIDS up to 1986.
Mid-1970's-1980 historyWe do not know how many people developed AIDS in the 1970s, or indeed in the years before. Neither do we know, and we probably never will know, where the AIDS virus HIV originated (see our origins page for some theories). But what we do know is:
"The dominant feature of this first period was silence, for the human immunodeficiency virus (HIV) was unknown and transmission was not accompanied by signs or symptoms salient enough to be noticed. While rare, sporadic case reports of AIDS and sero-archaeological studies have documented human infections with HIV prior to 1970, available data suggest that the current pandemic started in the mid- to late 1970s. By 1980, HIV had spread to at least five continents (North America, South America, Europe, Africa and Australia). During this period of silence, spread was unchecked by awareness or any preventive action and approximately 100,000-300,000 persons may have been infected." - Jonathan Mann 1 1981 HistoryKaposi's Sarcoma (KS) was a rare form of relatively benign cancer that tended to occur in older people. But by March 1981 at least eight cases of a more aggressive form of KS had occurred amongst young gay men in New York.2
At about the same time there was an increase, in both California and New York, in the number of cases of a rare lung infection Pneumocystis carinii pneumonia (PCP)3. In April this increase in PCP was noticed at the Centers for Disease Control (CDC) in Atlanta. A drug technician, Sandra Ford, noticed a high number of requests for the drug pentamine, used in the treatment of PCP:
"A doctor was treating a gay man in his 20s who had pneumonia. Two weeks later, he called to ask for a refill of a rare drug that I handled. This was unusual - nobody ever asked for a refill. Patients usually were cured in one 10-day treatment or they died" - Sandra Ford for Newsweek 4 In June, the CDC published a report about the occurrence, without identifiable cause, of PCP in five men in Los Angeles5. This report is sometimes referred to as the "beginning" of AIDS, but it might be more accurate to describe it as the beginning of the general awareness of AIDS in the USA.
A few days later, following these reports of PCP and other rare life-threatening opportunistic infections, the CDC formed a Task Force on Kaposi's Sarcoma and Opportunistic Infections (KSOI).6
Dr. Conant and Dr Volverg discussing
Kaposi's Sarcoma. Circa 1981
Around this time a number of theories were developed about the possible cause of these opportunistic infections and cancers. Early theories included infection with cytomegalovirus, the use of amyl nitrite or butyl nitrate "poppers", and "immune overload".7 8 9
Because there was so little known about the transmission of what seemed to be a new disease, there was concern about contagion, and whether the disease could by passed on by people who had no apparent signs or symptoms.10 Knowledge about the disease was changing so quickly that certain assumptions made at this time were shown to be unfounded just a few months later. For example, in July 1981 Dr Curran of the CDC was reported as follows:
"Dr. Curran said there was no apparent danger to non homosexuals from contagion. 'The best evidence against contagion', he said, 'is that no cases have been reported to date outside the homosexual community or in women'" - The New York Times 11 Just five months later, in December 1981, it was clear that the disease affected other population groups, when the first cases of PCP were reported in injecting drug users.12 At the same time the first case of AIDS was documented in the UK.13
1982 HistoryThe disease still did not have a name, with different groups referring to it in different ways. The CDC generally referred to it by reference to the diseases that were occurring, for example lymphadenopathy (swollen glands), although on some occasions they referred to it as KSOI, the name already given to the CDC task force.14 15
In contrast some still linked the disease to its initial occurrence in gay men, with a letter in The Lancet calling it "gay compromise syndrome".16 Others called it GRID (gay-related immune deficiency), AID (acquired immunodeficiency disease), "gay cancer" or "community-acquired immune dysfunction".17 18
In June a report of a group of cases amongst gay men in Southern California suggested that the disease might be caused by an infectious agent that was sexually transmitted.19
By the beginning of July a total of 452 cases, from 23 states, had been reported to the CDC.20
Later that month the first reports appeared that the disease was occurring in Haitians, as well as haemophiliacs.21 22 This news soon led to speculation that the epidemic might have originated in Haiti, and caused some parents to withdraw their children from haemophiliac camps.23
The occurrence of the disease in non-homosexuals meant that names such as GRID were redundant. The acronym AIDS was suggested at a meeting in Washington, D.C., in July.24 By August this name was being used in newspapers and scientific journals.25 26 27 AIDS (Acquired Immune Deficiency Syndrome) was first properly defined by the CDC in September.28
By the beginning of July a total of 452 cases, from 23 states, had been reported to the CDC
An anagram of AIDS, SIDA, was created for use in French and Spanish.29 Doctors thought AIDS was an appropriate name because people acquired the condition rather than inherited it; because it resulted in a deficiency within the immune system; and because it was a syndrome, with a number of manifestations, rather than a single disease.30
Still very little was known about transmission and public anxiety continued to grow.
"It is frightening because no one knows what's causing it, said a 28-year old law student who went to the St. Mark's Clinic in Greenwich Village last week complaining of swollen glands, thought to be one early symptom of the disease. Every week a new theory comes out about how you're going to spread it." - The New York Times 31 By 1982 a number of AIDS specific voluntary organisations had been set up in the USA. They included the San Francisco AIDS Foundation (SFAF), AIDS Project Los Angeles (APLA), and Gay Men's health Crisis (GMHC).32 In November 1982 the first AIDS organisation, the "Terry Higgins Trust" (later known as the Terrence Higgins Trust), was formally established in the UK, and by this time a number of AIDS organisations were already producing safer sex advice for gay men.33 34
In December a 20-month old child who had received multiple transfusions of blood and blood products died from infections related to AIDS.35 This case provided clearer evidence that AIDS was caused by an infectious agent, and it also caused additional concerns about the safety of the blood supply. Also in December, the CDC reported the first cases of possible mother to child transmission of AIDS.36
By the end of 1982 many more people were taking notice of this new disease, as it was clearer that a much wider group of people was going to be affected.
"When it began turning up in children and transfusion recipients, that was a turning point in terms of public perception. Up until then it was entirely a gay epidemic, and it was easy for the average person to say 'So what?' Now everyone could relate." - Harold Jaffe of the CDC for newsweek 37 It was also becoming clear that AIDS was not a disease that just occurred in the USA. Throughout 1982 there were separate reports of the disease occurring in a number of European countries.38
Meanwhile in Uganda, doctors were seeing the first cases of a new, fatal wasting disease. This illness soon became known locally as 'slim'.39
1983 HistoryIn January, reports of AIDS among women with no other risk factors suggested the disease might be passed on through heterosexual sex.40
At about the same time the CDC convened a meeting to consider how the transmission of AIDS could be prevented, and in particular to consider the newly emerged evidence that AIDS might be spread through blood clotting factor and through blood transfusions. As James Curran, the head of the CDC task force, said:
"The sense of urgency is greatest for haemophiliacs. The risk for others [who receive blood products] now appears small, but is unknown."41 The risk for haemophiliacs was so great because the blood concentrate that some haemophiliacs used exposed them to the blood of up to 5,000 individual blood donors.
In March, the CDC stated that,
"persons who may be considered at increased risk of AIDS include those with symptoms and signs suggestive of AIDS; sexual partners of AIDS patients; sexually active homosexual or bisexual men with multiple partners; Haitian entrants to the United States; present or past abusers of IV drugs; patients with haemophilia; and sexual partners of individuals at increased risk for AIDS." The same report also said,
"each group contains many persons who probably have little risk of acquiring AIDS... Very little is known about risk factors for Haitians with AIDS."42 Nevertheless, the inclusion of Haitians as a risk group caused much controversy. Haitian Americans complained of stigmatisation, officials accused the CDC of racism, and Haiti suffered a serious blow to its tourism industry.43 44 Before long people were talking colloquially of a "4-H Club" at risk of AIDS: homosexuals, haemophiliacs, heroin addicts and Haitians.45 46 Some people substituted hookers for haemophiliacs.47
In May 1983, doctors at the Institute Pasteur in France reported that they had isolated a new virus, which they suggested might be the cause of AIDS
In the UK there were public concerns about the blood supply with references in newspapers to "killer blood".48 The media more generally started to take notice of AIDS, with the screening of a TV Horizon programme, "The Killer in the Village", and a number of newspaper articles on the subject of the "gay plague".49 50
In May 1983, doctors at the Institute Pasteur in France reported that they had isolated a new virus, which they suggested might be the cause of AIDS.51 Little notice was taken of this announcement at the time, but a sample of the virus was sent to the CDC.52 A few months later the virus was named lymphadenopathy-associated virus or LAV, patents were applied for, and a sample of LAV was sent to the National Cancer Institute.53
But whilst progress was being made by scientists there was at the same time increasing concern about transmission, and not just in relation to the blood supply. A report of AIDS occurring in children suggested quite incorrectly the possibility of casual household transmission.54
AIDS transmission became a major issue in San Francisco, where the Police Department equipped patrol officers with special masks and gloves for use when dealing with what the police called "a suspected AIDS patient".
"The officers were concerned that they could bring the bug home and their whole family could get AIDS." - The New York Times 55 And in New York:
"landlords have evicted individuals with AIDS" and "the Social Security Administration is interviewing patients by phone rather than face to face." - Dr David Spencer, Commisioner of Health, New York City 56 There was considerable fear about AIDS in many other countries as well:
"In many parts of the world there is anxiety, bafflement, a sense that something has to be done - although no one knows what." - The New York Times 57 As anxiety continued, the CDC tried to provide reassurance that children with AIDS had probably acquired it from their mothers and that casual transmission did not occur:
"The cause of AIDS is unknown, but it seems most likely to be caused by an agent transmitted by intimate sexual contact, through contaminated needles, or, less commonly, by percutaneous inoculation of infectious blood or blood products. No evidence suggests transmission of AIDS by airborne spread. The failure to identify cases among friends relatives, and co-workers of AIDS patients provides further evidence that casual contact offers little or no risk [...] the occurrence in young infants suggests transmission from an affected mother to a susceptible infant before, during, or shortly after birth."58 Reports from Europe suggested that two rather separate AIDS epidemics were occurring. In the UK, West Germany and Denmark, the majority of people with AIDS were homosexual, and many had a history of sex with American nationals. However in France and Belgium AIDS was occurring mainly in people from Central Africa or those with links to the area.59
Examples of this second epidemic included a number of previously healthy African patients who were hospitalised in Belgium with opportunistic infections (such as PCP and cryptosporidosis), Kaposi's sarcoma, or other AIDS-like illnesses. All of these Africans had immune deficiency similar to that of American AIDS patients. However they had no history of blood transfusion, homosexuality, or intravenous drug abuse.60 In light of such reports, European and American scientists set out to discover more about the occurrence of AIDS in Central Africa.
By this time, doctors working in parts of Zambia and Zaire had already noticed the emergence of a very aggressive form of Kaposi's sarcoma. This cancer was endemic in Central Africa, but previously it had progressed very slowly and responded well to treatment, whereas the new cases looked very different and were often fatal.61 62
In September the CDC published their first set of recommended precautions for health-care workers and allied professionals designed to prevent "AIDS transmission".63 In the UK, people who might be particularly susceptible to AIDS were asked not to donate blood.64
In October, the first European World Health Organisation (WHO) meeting was held in Denmark. At the meeting it was reported that there had been 2,803 AIDS cases in the USA.65
That meeting was followed in November by the first meeting to assess the global AIDS situation. This was the start of global surveillance by the WHO and it was reported that AIDS was present in the U.S.A., Canada, fifteen European countries, Haiti and Zaire as well as in seven Latin American countries. There were also cases reported from Australia and two suspected cases in Japan.66
By the end of the year the number of AIDS cases in the USA had risen to 3,064 and of these 1,292 had died.67
1984 HistoryAt the CDC researchers had been continuing to investigate the cause of AIDS through a study of the sexual contacts of homosexual men in Los Angeles and New York. They identified a man as the link between a number of different cases and they named him "patient O" for "Out of California".68 The research appeared to confirm that AIDS was a transmittable disease, and the co-operation of "patient O" contributed to the study.69
However a problem arose when other people read the scientific paper.
"I called this guy Patient O... But my colleagues read it as Patient Zero." - Darrow for Newsweek 70 And so in March 1984 the myth of Patient Zero began.71 See 1987 for more information about Patient Zero.
Just one month later, on April 22nd, Dr Mason of the CDC was reported as saying:
"I believe we have the cause of AIDS." He was referring to the French virus, LAV, and he was basing his opinion on the findings made in the preceding weeks by the researchers at the Pasteur Institute who had discovered the virus the previous year.72
Margaret Heckler
Just one day later, on April 23rd, the United States Health and Human Services Secretary Margaret Heckler announced that Dr. Robert Gallo of the National Cancer Institute had isolated the virus which caused AIDS, that it was named HTLV-III, and that there would soon be a commercially available test able to detect the virus with "essentially 100 percent certainty". It was a dramatic and optimistic announcement that also included:
"We hope to have a vaccine [against AIDS] ready for testing in about two years." And it concluded with:
"yet another terrible disease is about to yield to patience, persistence and outright genius".73 74 The same day patent applications were filed covering Gallo's work, but there was clearly a possibility that LAV and HTLV-III were the same virus.75 76 The scientific papers regarding Gallo's discovery of HTLV-III were published on 4th May.77 By 17th May, private companies were already applying to the Department of Health & Human Services for licences to develop a commercial test, which would detect evidence of the virus in blood, a test which it had already been said would be used to screen the entire supply of donated blood in the USA.78 79
Meanwhile there continued to be concern about the public health aspects of AIDS. This was particularly the case in San Francisco where all the gay bath houses and private sex clubs were closed. Some gay men regarded the closures as an attack on their civil rights. But Mervyn Silverman, Director of the San Francisco Department of Public Health stated the public health view as follows:
Dr Robert Gallo
"There are certain places where things are allowed and certain places where they are not. You can't have sex at the McDonald's. You generally cannot have sex in the pews of a church or in a synagogue. People don't feel their civil liberties are being in any way abrogated because of that."80 Researchers who had visited Central Africa in late 1983 reported they had identified 26 patients with AIDS in Kigali, Rwanda, and 38 in Kinshasa, Zaire. The Rwandan study concluded that, "an association of an urban environment, a relatively high income, and heterosexual promiscuity could be a risk factor for AIDS in Africa".81 The Zairian study found there to be a "strong indication of heterosexual transmission".82
In light of these findings the Zairian Department of Public Health, in collaboration with American and European scientists, launched a national AIDS research programme called Project SIDA.83
By the end of 1984, there had been 7,699 AIDS cases and 3,665 AIDS deaths in the USA, and 762 cases had been reported in Europe.84 85 In the UK there had been 108 cases and 46 deaths.86
1985 HistoryIn January 1985 a number of more detailed reports were published concerning LAV and HTLV-III, and by March it was clear that the viruses were the same.87 The same month the U.S Food and Drug Administration (FDA) licensed, for commercial production, the first blood test for AIDS. The test would reveal the presence of antibodies to HTLV-III/LAV, and it was announced that anyone who had antibodies in their blood would not in future be allowed to donate blood.88
There were a number of social and ethical issues, as well as certain medical matters, that had to be considered before the new test could be used even to ensure the safety of the blood supply. And even more aspects needed to be considered before the test could be more widely used. Concern particularly centred on issues of confidentiality and the meaning of a positive test result.89 90
"Richard Dunne, director of the Gay Men's Health Crisis, said that the group would not object to the wider availability of the procedure provided that certain safeguards were assured: informed consent, good counselling and confidentiality, 'which means anonymity,' he said. He stressed that the city must prevent insurance companies, employers, schools and others from gaining access to test results." - The New York Times 91 The first small-scale needle and syringe exchange project had been started in 1984 in Amsterdam, the Netherlands, but more projects were started in 1985 as a result of growing concerns about HTLV-III/LAV.92
In April more than 2000 people attended the first international Conference on AIDS held in Atlanta. Three major topics of discussion were the new HTLV-III/LAV test, the situation with regard to AIDS internationally, and the extent of heterosexual transmission.93
"Some experts are sceptical that AIDS will spread as rapidly among heterosexuals as it has among homosexuals. Yet other experts, taking their cues from data emerging from preliminary studies from Africa showing equal sex distribution among males and females, are less sure." - The New York Times 94 Immediately after the conference, the World Health Organization (WHO) organized an international meeting to consider the AIDS pandemic and to initiate concerted worldwide action.95
Meanwhile in many countries there was a separate "epidemic of fear" and prejudice.96
In the UK tabloid press, AIDS gained many headlines and caused alarm among the public. In some newspapers, the prejudice was obvious. The haemophiliacs were seen as the "innocent victims" of AIDS whereas gays and drug-users were seen as having brought the disease upon themselves.97 The fear of AIDS caused firemen to ban the kiss of life, and caused holidaymakers to cut their holiday short for fear of contracting AIDS from an HTLV-III positive passenger on the Queen Elizabeth 2.98 99 A 9-year old HTLV-III positive haemophiliac was allowed to attend the local school, but some of the pupils where kept home by anxious parents.100
In the US, it was feared that drinking communion wine from a common cup could transmit AIDS, and Ryan White, a 13-year old haemophiliac with AIDS, was barred from school.101 102
"In 1985, at 13, Ryan White became a symbol of the intolerance that is inflicted on AIDS victims. Once it became known that White, a haemophiliac, had contracted the disease from a tainted blood transfusion, school officials banned him from classes." - Time Magazine 103 The CDC removed Haitians from their list of AIDS risk groups, in light of information that suggested both heterosexual contact and exposure to contaminated needles played a role in transmission.104
On September 17th, President Reagan publicly mentioned AIDS for the first time, when he was asked about AIDS funding at a press conference. At the same press conference he was also asked a question whether he would send his children if they were younger to school with a child who has AIDS.
"It is true that some medical sources had said that this cannot be communicated in any way other than the ones we already know and which would not involve a child being in the school. And yet medicine has not come forth unequivocally and said, 'This we know for a fact, that it is safe.' And until they do, I think we just have to do the best we can with this problem. I can understand both sides of it." - Ronald W. Reagan 105 Drugs such as ribavirin, thought to be active against HTLV-III/LAV, were being smuggled from Mexico into the USA.106
The actor Rock Hudson died of AIDS on October 3rd 1985. He was the first major public figure known to have died of AIDS.107
All UK blood transfusion centres began routine testing of all blood donations for HTLV-III/LAV in October.108
For the Global Surveillance of AIDS, the WHO had initially used the definition of AIDS as developed in the USA in 1982. But this definition was difficult to use in developing countries where there was a lack of sophisticated laboratory tests. So in order to help with the surveillance of AIDS, particularly in Africa, a new WHO definition was adopted in October. This definition of AIDS became known as the Bangui definition.109
Towards the end of the year, Western scientists became much more aware of the "slim disease" that had become increasingly common in South West Uganda since 1982. Studies found that most cases were among promiscuous heterosexuals, the majority of whom tested positive for antibodies to HTLV-III/LAV. The site and timing of the first reported cases suggested that the disease arose in neighbouring Tanzania. Some scientists who studied slim concluded: "Although slim disease resembles AIDS in many ways, it seems to be a new entity."110 . However, others thought differently:
"[Evidence] suggests that slim disease cannot be distinguished from AIDS and ARC [AIDS related complex] by extreme weight loss and diarrhoea. Thus slim disease may not be a new syndrome but simply identical with AIDS as seen in Africa."111
In December 1985, the Pasteur Institute filed a lawsuit against the National Cancer Institute to claim a share of the royalties from the NCI's patented AIDS test.112
During the year, knowledge of transmission routes was to change again, when the first report appeared of the transmission of the virus from mother to child through breast feeding.113 The first case of AIDS was also reported in China, and AIDS had as a result been reported in every region in the world.114
By the end of 1985, 20,303 cases of AIDS had been reported to the World Health Organisation.115 In the USA 15,948 cases of AIDS had been reported,116 and in the UK 275 cases.117
1986 HistoryThe first UK needle exchange scheme started in Dundee in February.118
In the UK, the government launched, in March, the first public information campaign on AIDS, with the slogan "Don't Aid AIDS". There were a series of advertisements in national newspapers.119
There was still at this time disagreement about the name of the virus.
"The name of the virus had itself become a political football as the French insisted on LAV (lymphadenopathy-associated virus), while Gallo's group used HTLV-3 (human T-cell lymphotropic virus, type 3)." - Time Magazine 120 In May 1986, the International Committee on the Taxonomy of Viruses ruled that both names should be dropped and the dispute solved by a new name, HIV (Human Immunodeficiency Virus).121
At the opening speech of the International Conference in Paris, held from 23rd to 25th June 1986, Dr H Mahler, the Director of WHO, announced that as many as 10 million people worldwide could already be infected with HIV.122
In August, the USA Federal Government accused an employer of illegal discrimination against a person with AIDS for the first time. A hospital had dismissed a nurse and refused to offer him an alternative job. This was seen as a violation of his civil rights.123
In September there was dramatic progress in the provision of medical treatment for AIDS, when early results of clinical tests showed that a drug called azidothymidine (AZT) slowed down the attack of HIV. AZT was first synthesised in 1964 as a possible anticancer drug but it proved ineffective.
The AZT clinical trial divided patients into two groups: one received AZT and the other received placebo, or dummy drugs. At the end of six months, only one patient in the AZT group was dead, whilst there were 19 deaths among the placebo group. The clinical trial was stopped early, because it was thought to be unethical to deny the patients of the placebo groups a better chance of survival.124
"The announcement set off a flurry of excitement and controversy. AIDS hotlines and doctors' offices were flooded with calls, community leaders warned about undue optimism, and doctors debated the ethical and medical issues raised by the early cancellation of the AZT study." - Time Magazine 125 In the United States, the Surgeon General's Report on AIDS was published. The report was the Government's first major statement on what the nation should do to prevent the spread of AIDS. The "unusually explicit" report urged parents and schools to start "frank, open discussions" about AIDS.126
By this time, scientists had accumulated enough evidence to form an overview of AIDS in Africa. Studies of medical records showed there had been marked increases in a number of AIDS-related conditions during the late 1970s and early 1980s. In particular:
Slim disease in Kinshasa, Zaire (late 1970s) Slim disease in Uganda and Tanzania (early 1980s) Esophagel candidiasis in Rwanda (from 1983) Aggressive Kaposi's sarcoma in Kinshasa, Zaire (early 1980s) Aggressive Kaposi's sarcoma in Zambia and Uganda (from 1982 and 1983) Crypotococcal meningitis in Kinshasa, Zaire (late 1970s to early 1980s). In conclusion:
"These studies suggested that while isolated cases of AIDS may have occurred in Africa earlier, it was probably rare until the late 1970's and early 1980's, a pattern similar to that in the United States and Haiti."127 As in developed countries, AIDS in Africa was found to primarily affect young and middle-aged people, especially those who were unmarried. The sex and age distributions were seen to reflect other sexually transmitted diseases, and the major transmission routes had been identified:
"Available data suggest that heterosexual activity, blood transfusions, vertical transmission from mother to infant, and probably frequent exposure to unsterilized needles account for the spread of HIV infection and AIDS in Africa."128 HIV and AIDS had also been detected in India, among sex workers in the southern state of Tamil Nadu, igniting fears that the disease would soon spread across the subcontinent. In response, the Indian government decided to increase the number of HIV testing centres and improve the screening of blood donations.129
By the end of the year, 85 countries had reported 38,401 cases of AIDS to the World Health Organisation. By region these were: Africa 2,323, Americas 31,741, Asia 84, Europe 3,858, and Oceania 395.130./by Annabel Kanabus and Jenni Fredriksson.

Cancerous cells isolated by freezing, then killed with drugs

Cancerous cells isolated by freezing, then killed with drugsIndependent, The (London), May 15, 2002 by Lorna Duckworth Health Correspondent
CANCERS HAVE been successfully frozen to the brink of death, enabling them to be wiped out with powerful drugs, researchers said yesterday.
The tumours are killed by inserting ice-cold metallic probes to freeze the cancerous cells. Once frozen, the outer barriers of the cells become leaky, allowing large molecules such as anti-cancer drugs to pass through the cell membranes.
Researchers from France and America believe that the technique, called cryochemotherapy, will prove highly potent as well as more selective than conventional treatments. A report in the British Journal of Cancer yesterday said that the frozen probes could be precisely directed, leaving healthy tissue unharmed.

Until now, procedures using freezing have had limited success because the survival of even a handful of cells means that the tumour can regrow.
But Dr Lluis Mir, from the Gustave-Roussy Institute near Paris, and Dr Boris Rubinsky, from the University of California at Berkeley, decided to combine freezing with chemo-therapy. They treated frozen cancer cells with a drug called Bleomycin, which is potentially highly toxic to cells, but is usually unable to pass through their membranes. Their experiments showed that hardly any cancerous cells survived the combined treatment.
Dr Mir said: "Frozen tissues show up very clearly on scanning images, so it is a simple matter to ensure you are giving the cold probes to the tumour and avoiding the healthy tissue. Although the drug we are using is extremely toxic, it can only enter cells that have been frozen, which means that unfrozen healthy tissue will be left unaffected."
Preclinical trials are due to start shortly, but Dr Mir said the treatment would not be available for patients for some time.
l Cancer-causing chemicals have now overtaken heart disease as the number one killer of Europeans aged between 35 and 65, MPs were warned at a Commons meeting. Dr Claude Reiss, a molecular toxicologist, said experts agreed that 80 to 90 per cent of cancers - 1 million casualties per year in the EU - were attributable to carcinogenic chemicals present in the environment.
Copyright 2002 Independent Newspapers UK LimitedProvided by ProQuest Information and Learning Company. All rights

Researchers show how new chemotherapy drugs kill cancerous tumors

Researchers show how new chemotherapy drugs kill cancerous tumors Medical Research News
University of Manchester researchers are investigating exactly how chemotherapy drugs kill cancerous tumours in a bid to reduce side effects and test the effectiveness of safer new agents. Dr Stephen Taylor and Karen Gascoigne at the University of Manchester's Faculty of Life Sciences have taken a new systematic approach to studying anti-mitotic drugs, which are used extensively for breast or ovarian cancer in the UK.
This class of drugs, which includes the agent taxol, has been used clinically for many years because they are highly effective. However, as in all chemotherapy, there are side effects. In the case of taxol these include peripheral neuropathies which can lead to permanent nerve damage and loss of sensation in fingers.
In addition little is known about how anti-mitotic drugs work, despite a lot of research on them, because many studies were population-based approaches that were indirect and led to vague and confusing interpretations.
Dr Taylor said: "To bypass the neurotoxicity, new anti-mitotics are being generated. Early clinical studies show that these drugs do not result in significant neurotoxicity. The big question now is whether they will have anti-tumour effects.
"To help determine this, we need to know which types of tumours are likely to be sensitive to these new agents, and which ones are likely to be resistant. This would allow clinicians to better design the clinical trials, i.e. you only recruit patients who are likely to respond. In addition, if the drugs show promise, then it would pave the way for patient stratification in the future, again allowing oncologists to identify which patients are likely to benefit from these drugs in advance of treatment.
"To predict which types of tumours are likely to respond, we first need to know how anti-mitotic drugs work, both the classical drugs and these new agents."
He and Ms Gascoigne, whose findings are published in the journal Cancer Cell (August 2008), have shown how different tumours respond to the anti-mitotic drugs - which target the mitotic spindle (the structure that separates the chromosomes during cell division) - and revealed that the variation in cell behaviour was far greater than previously recognized.
They used a high throughput automated time-lapse light microscopy approach to systematically analyze over 10,000 single cells from 15 cell lines in response to three different classes of anti-mitotic drug. This revealed the large variation in cell behavior with cells within any given line exhibiting multiple fates.
Dr Taylor explained: "We know that anti-mitotic drugs block the final stage of the cell division process, mitosis. How the cells then die is a mystery.
"We embarked on a fresh, more direct approach that is actually quite simple. Basically, we just watched the cells using time-lapse microscopy; this allowed us to track the behaviour of individual cells and determine their fate when exposed to different anti-mitotic drugs.
"The first thing we realised was that the picture was much more complicated that we originally thought; the range of different behaviours was profound. Not only did cells from different cell lines behave differently, but cells within the same line also behaved differently.
"The level of complexity was at first overwhelming. However, as we slowly made our way through the data, patterns began to emerge. This allowed us to formulate a new hypothesis. We were then able to design more experiments to test this hypothesis.
"In essence, it turns out that when cells are exposed to these drugs they arrest in mitosis. Then a race starts between two competing cellular signalling networks. One network is trying to kill the cell, the other is trying to cause the cell to exit mitosis and thus allow the cell to survive. The winner of the race decides the fate of the cell; death or survival.
"The factors influencing the race not only vary from cell line to cell line, but also within cells from the same line, explaining why there is so much complexity.
"What we want to do now is figure out how we can help the cell death pathway win the race more often; this would hopefully mean that the anti-mitotic drugs would be better at killing cancer cells. First we want to test this idea in the lab but hopefully in the longer run this will mean that these drugs can be used more effectively in the clinic."
He added: "Karen, a talented graduate student, worked very hard on this study and the work was only possible because the Faculty recently bought a fully automated microscope that allowed us to analyse such large numbers of cells. We acquired this state-of-the-art microscope thanks to the University's Strategic Research Fund, which demonstrates the University's commitment to cancer research.
"Our systematic, single-cell-based approach to describe how different tumour cells respond to these drugs has given a data set that provides an invaluable resource and an intellectual framework for dissecting how anti-mitotic agents kill tumour cells."

Viagra shown to prevent heart damage

Viagra shown to prevent heart damage
Pill shown to target form of muscular dystrophyCharlie Fidelman , Montreal Gazette; Canwest News ServiceMONTREAL - It seems there's just no stopping the little diamond-shaped blue pill. Viagra can help treat erectile dysfunction, reduce pulmonary hypertension, prevent flowers from wilting -- and according to a Montreal study -- the anti-impotence pill is also good for ailing hearts.
In a study led by Christine Des Rosiers at the Montreal Heart Institute, Viagra's active ingredient -- sildenafil citrate -- seems to prevent heart damage caused by Duchenne muscular dystrophy.
The drug improved the heart performance of mice that were engineered to develop this common form of muscular dystrophy. The mice were given a dose roughly equivalent to what men with erectile dysfunction take.

The findings reveal a potential new treatment to ward off cardiac complications in patients suffering from Duchenne muscular dystrophy, a genetic disease that affects roughly one in 3,600 males.
The first signs of the illness usually appear around age five.
The muscle-wasting illness leads to muscle weakness, scoliosis, heart problems and obesity. Few patients survive beyond age 25.
Heart failure is usually the cause of death.
Viagra is already prescribed to treat such problems as erectile dysfunction, pulmonary hypertension and altitude sickness.
The drug is shown to be safe, but it's too premature to give it to people to help treat muscular dystrophy, Des Rosiers cautioned.
"There is no cure around the corner. We need formal clinical trials to go from what we saw to prescribing Viagra to children to prevent damage," she said.
The study was published Tuesday in the online edition of the Proceedings of the National Academy of Sciences

20 Ways to Eliminate Stress From Your Life

20 Ways to Eliminate Stress From Your Life
You often see articles on ways to unwind and relax after a stressful day, which I always find useful, but for me the most important advice would be to get to the source of the problem, and cut stress out before it even happens.
By careful editing of your life, and changing certain habits, you can eliminate most (not all) sources of stress in your life.
I don’t believe that a stress-free life is possible. Stress is a response to challenges in life, and a life without challenges is too boring to contemplate. However, I do believe that most of the stress in our lives is unnecessary, and that it can be eliminated by taking some simple (and some not-so-simple) steps. It can’t be accomplished overnight — I’ve been eliminating stressors in my life for awhile now, and I’m still not done. But I think it’s a worthwhile goal.
Let’s first take a look at an example — it’s a little extreme, but it exemplifies the typical stressors in people’s lives. Let’s say Fred gets up in the morning, waking up late, and now has to rush to get ready. He’s so rushed that he spills his coffee on his shirt and has to change, a nicks himself shaving. He heads out the door and then has to go back in the house because he forgot his wallet. He gets in the car and realizes he forgot his keys.
Now he’s on the way in to work and is in the middle of rush-hour traffic — and his temper starts to flare after someone cuts him off. He’s honking at people, cursing, and arrives to work late and in a bad mood. He snaps at someone and is surly all morning. His desk is covered in piles of paper, and he can’t find that report he needs to work on. His inbox is overflowing and his email notification is going off, and he sees he has 36 messages to respond to. He knows he’s late on two projects and his boss isn’t happy. He’s got to finish 5 tasks before the 11 a.m. meeting, and he’s got meetings all afternoon.
You get the idea. His day does not go well, and he hits rush-hour traffic on the way home. He gets home late, exhausted, completely stressed, his mind still on his late and as-yet uncompleted projects, his still-full inbox and email inbox, and all the stuff piling up that he has to work on tomorrow. The house is a mess and he snaps at his family. His kids have not put things away exactly where he told them to put them away, so he begins to yell at them. He has a quick, greasy dinner in front of the TV and zones out before falling asleep late.
Again, this is a bit extreme, but you can see through this illustration some of the things that stress people out. There are many more, of course, and I won’t cover all of them here.
But these sources of stress can be eliminated with a little thought. Here’s how:
1. Identify stressors. This is the most important step of all, as identifying the things that stress you out in your life is the first step towards eliminating them. Take 10 minutes to think about what stresses you out during the day. What weekly occurrences stress you out? What people, activities, things cause stress in your life? Make a Top 10 list, and see which of them can be eliminated, and start to weed them out. For those that can’t, find ways to make them less stressful. 2. Eliminate unnecessary commitments. I did a post on editing your commitments before … apply those concepts here. We all have many commitments in our life, starting with work but also including commitments related to kids, our spouses, things to do at home, other family, civic, side work, religious, hobbies, online activities and more. Consider each of them, the amount of stress they provide, and the value you get out of them. Edit brutally, and take steps today to remove the ones that stress you out the most. 3. Procrastination. We all do this, of course. But allowing stuff to pile up will stress us out. Find ways to take care of stuff now (form a Do It Now habit) and keep your inbox and desk clear. See 20 Procrastination Hacks for more ideas. 4. Disorganization. We’re all disorganized to some extent. Even if we’ve organized something, and created a great system for keeping it that way, things tend to move towards chaos over time. But disorganization stresses us out, in terms of visual clutter, and in making it difficult to find stuff we need. Take time to get things in your life organized, starting with your desk and the papers in your home, and moving on to other areas. 5. Late. Being late always stresses us out. We have to rush to get ready, rush to get there, and stress out the whole time about looking bad and being late. Learn the habit of being early, and this stress disappears. Make a conscious effort to start getting ready earlier, and to leave earlier. This also makes driving less stressful. Time yourself to see how long it actually takes to get ready, and how long it actually takes to get somewhere. You’ve probably been underestimating these times. Once you know these times, you can plan backwards so that you show up 10 minutes early each time. It’s a good feeling. 6. Controlling. We are not the Master of this Universe. I know we sometimes wish we were, but acting as if we are is a sure way to get stressed out. Trying to control situations and people cannot work, and only serves to increase our anxiety when it doesn’t work. Learn to let go, and accept the way that other people do things, and accept what happens in different situations. The only thing you can control is yourself — work on that before you consider trying to control the world. Also learn to separate yourself from tasks and to delegate them. Learning to let go of our need to control others and the situations around us is a major step towards eliminating stress. 7. Multitasking. Having multiple tasks going on at the same time might seem productive, but in actuality it slows us down from actually focusing on a task and completing it — and it stresses us out in the meantime. Learn to single-task. 8. Eliminate energy drains. If you’ve analyzed your life (in Step 1) and found things that stress you out, you might have also noticed things that drain your energy. Certain things in our life just cause us to be more exhausted than others, with less value. Identify them, and cut them out. You’ll have much more energy and much less stress. Happiness ensues. 9. Avoid difficult people. You know who they are. If you take a minute to think about it, you can identify all the people in your life — bosses, coworkers, customers, friends, family, etc. — who make your life more difficult. Now, you could confront them and do battle with them, but that will most certainly be difficult. Just cut them out of your life. 10. Simplify life. Simplifying, of course, is a major theme of Zen Habits. Simplify your routines, your commitments, your information intake, your cluttered rooms, the mass of stuff going on in your life … and have less stress as a result. Start with Edit Your Life and then look through the other simplicity articles. 11. Unschedule. Create more open periods of time in your life. It’s not necessary to schedule every minute of our lives. Learn to avoid meetings, keep wide open blocks of time where we either work on our important tasks or batch process the smaller ones. When someone asks to schedule a meeting, first try to get it done through email or phone … if that doesn’t work, avoid having it scheduled. Ask them to call you and see if you’re free at that time. You will love having an open schedule. 12. Slow down. Instead of rushing through life, learn to take things slow. Enjoy your food, enjoy the people around you, enjoy nature. This step alone can save tons of stress. 13. Help others. It may sound contradictory to add more tasks to your life by trying to help other people (you’ve got enough to do), but if you were to add anything to your life, this should be it. Helping others, whether volunteering for a charity organization or just making an effort to be compassionate towards people you meet, not only gives you a very good feeling, it somehow lowers your stress level. Of course, this doesn’t work if you try to control others, or help others in a very rushed and frenetic way — learn to take it easy, enjoy yourself, and let things happen, as you work to make the lives of others better. 14. Relax throughout the day. It’s important to take mini-breaks during your work day. Stop what you’re doing, massage your shoulders and neck and head and hands and arms, get up and stretch, walk around, drink some water. Go outside and appreciate the fresh air and the beautiful sky. Talk to someone you like. Life doesn’t have to be all about productivity. You should also avoid using online activity too much as your de-stressing activity — get away from the computer to relax. 15. Quit work. This one’s drastic, and probably too drastic for most. But in most likelihood, your work is your absolute biggest stressor. Getting out of your 9-to-5, automating your income, and finding something you truly love to do, that you’re passionate about, will create a positive life and much less stressful one at that. Give it a little thought before dismissing it — there might be possibilities here you haven’t considered. 16. Simplify your to-do list. I’ve written about this before, but attempting to do everything on your long to-do list will definitely stress you out. Learn to simplify your to-do list down to the few essential tasks, and you will enjoy the process much more. 17. Exercise. This is common advice for stress relief, and that’s because it works … but it’s also a stress prevention method. Exercising helps relieve the stress buildup, it gives you some quiet time to contemplate and relax, and just as importantly, it makes you more fit. A fitter person is better equipped to handle stress. Another important factor: being unhealthy can be a major stressor (especially once you have to go to the hospital), and exercise can help prevent that. 18. Eat healthy. This goes hand-in-hand with exercise as a stress prevention method, of course. Become healthier and a major source of stress will disappear. Also, I’ve found that greasy food, for me, puts me in a worse mood and can contribute to stress levels immediately. 19. Be grateful. This might not be as obvious as some of the others, but developing an attitude of gratitude (I sound like a preacher with that rhyme!) is a way of thinking positive, eliminating negative thinking from your life, and thereby reducing stress. Learn to be grateful for what you have, for the people in your life, and see it as a gift. With this sort of outlook on life, stress will go down and happiness will go up. That’s a winning formula. 20. Zen-like environment. Take time to declutter your desk (as mentioned above) and even once you do that, continually edit your desk and working space, and the things in your home, until you’ve created a simple, peaceful, Zen-like environment. It will be much less stressful to work in an environment like that than a more cluttered and distracting

The Effects of Smoking

The Effects of Smoking

Smokers who have heart failure can automatically eliminate a major source of damage to their heart by quitting. Each puff of nicotine from tobacco smoke temporarily increases heart rate and blood pressure, even as less oxygen-rich blood circulates through the body. Smoking also leads to clumping or stickiness in the blood vessels feeding the heart. People who quit smoking are more likely to have their heart failure symptoms improve.
Lifetime smokers often need help to quit successfully. The healthcare team can provide information about smoking cessation programs, as can the American Lung Association and the American Cancer Society. These tips may also help smokers quit:
Keep busy doing things that make it hard to smoke, like working in the yard, washing dishes and being more active. Fight the urge by going to places where smoking isn't allowed and staying around people who don't smoke. Avoid situations that tempt you to smoke, like drinking coffee or alcohol. Find a substitute to reach for instead of a cigarette. Try a hard candy. Don't give up if you smoke a cigarette. Just resolve not to do it again. Remind yourself that you're likely to feel better if you stop smoking. Tell family members and friends that you need to quit smoking and need their support. If your husband, wife, son or daughter smokes, ask them to quit with you.
This content is reviewed regularly. Last updated 12/13/


By Dr Langlet Philippe, Hepato-gastroenterology department, Brugmann University Hospital, Brussels.
1.Clinical presentation2.Investigations3.Prognosis4.Therapy5.Conclusions

Alcoholic liver disease (ALD) is one of the major medical complications of alcohol abuse and a major health economic problem in the western world.Alcohol is the major cause of liver cirrhosis in the Western world whereas alcoholic cirrhosis is responsible for approximately 44% of the 26000 death cirrhosis in the United States each years.
Safe limits for alcohol intake
The safe limits for alcohol intake are controversial but it is generally advised a weekly limit of 21 units (210g) of alcohol in men and 14 units in women.Although there is steep dose dependent increase in ALD risk above this threshold with increasing alcohol intake, there is an heterogeneity of the patient population with regard to disease severity and individual susceptibility to alcohol-related liver injury.

Factors increasing susceptibility to ALD
- Women at any given level of intake. - Lifetime intake of alcohol - Genetic factors - Drinking without food - Binge drinking - High concentration alcoholic drinks (spirits,…) - Drinking multiple different alcoholic beverages
It is estimated ,as shown in Figure 1, that although 90-100% of heavy drinkers show evidence of fatty liver, only 10-35% develop alcoholic hepatitis and 8-20% develop cirrhosis.

Figure 1.
Progression of alcoholic liver diseasein heavy drinkers.

Spectrum of liver disease
The three most widely recognised forms of ALD are alcoholic fatty liver (steatosis), acute alcoholic hepatitis, and alcoholic cirrhosis.
Steatosis appears invariably if consumption exceeds 80 g of alcohol per day. In this pathology, cytoplasm of affected hepatocytes is occupied by a single large triglyceride occlusion. Liver function is often normal and steatosis is reversible with abstinence.
Acute Alcoholic hepatitis
In alcoholic hepatitis , the typical histologic picture includes hepatocellular necrosis and ballooning degeneration, alcoholic Mallory's hyaline bodies and an inflammatory reaction with many polymorphonuclear leukocytes (sattelitosis). It is estimated that 15-20 years of excessive drinking is necessary to develop alcoholic hepatitis. Cholestasis is prominent. It is more severe in females and also in Nothern Europeans and unrelated to pattern of drinking or type of alcohol drink. High mortality rates are seen (30-60%) and patients often deteriorate after hospital admission despite abstinence. Alcoholic hepatitis has been established as an important precursor to the formation of cirrhosis.
The most severe form of alcoholic liver injury and usually of the micronodular type. The risk is increased in continuous drinkers. Survival for patients is 60%-70% at one year and 35%-50% at five years.
Most evidence indicates that the principal cause of alcohol-induced liver injury is cellular toxicity resulting from acetaldehyde.Ethanol is oxidised to acetaldehyde in the mitochondria by alcohol dehydrogenase, which in turn is oxidised to acetate by acetaldehyde dehydrogenase. These oxydation reactions alter the cellular metabolism with harmful effects on lipid and carbohydrate metabolism- for example, steatosis. Oxygen derived free radicals may cause direct hepatocyte injury by lipid peroxydation whereas acetaldehyde binds covalently to proteins forming adducts and may serve as neoantigens. This binding initiates harmful humoral and/or cellular immune responses, which leads to tissue injury.
The expression of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-a), transforming growth factor-beta (TGF-ß), interleukin (IL)-1ß and IL-6 are increased in alcoholic liver injury while the anti-inflammatory cytokine, IL-4 is decreased. These cytokines stimulate stellate cells which produce collagen leading to liver fibrosis. Moreover, in patients with alcoholic hepatitis, malnutrition leads to a reduction of the antioxydant defence mechanisms and contribute to the development of alcohol induced injury.
Clinical presentation
The clinical presentation of alcoholic hepatitis varies greatly with the severity of disease. Common symptoms are weakness, anorexia, weight loss, nausea, vomiting and diarrhea. Patients with alcoholic hepatitis are often malnourished and pyrexial. Pain in the right upper quadrant, jaundice, and fever may be present and can wrongly lead to a diagnosis of biliary tract disease. On physical examination, there is often marked hepatomegaly which is tender on palpation. Hepatic bruits may be heard. Splenomegaly is uncommon. Ascites and hepatic encepalopathy are common in severe disease but varices are not common.
Upper gastrointestinal bleeding does occur but is usually due to gastric erosions or peptic ulceration on a backgroung of coagulopathy Infections are very common.Often patients have co-existence of alcoholic hepatitis and cirrhosis with clinical features such as spider telangiectasia, parotid enlargement, gynecomastia.

Laboratory findings
Table 1.Common laboratory findings in alcoholic hepatitis
Leukocytosis with shift to the left AST 2 to 3 times higher than ALT (ALT usually < 100 IU/L) Increased serum bilirubin level; correlates with severityProlonged prothrombin time; correlates with severity Decreased serum albumin level Increased serum IgA and IgG levelsDecreased serum cholesterol levelDecreased serum triiodothyronine level
-Serum transaminases levels are often not greatly raised in ALD and values greater than five times the upper limit of the normal reference range should lead to consideration of other diagnoses such as viral or autoimmune hepatitis.- Hyperbilirubinemia reflects the severity of the hepatitis and could be greatly increased in alcoholic hepatitis.- Prolongation of the prothrombin time and hypoalbuminemia reflect poor hepatic synthetic function.- Leukocytosis is common and a count of polymorphonuclear leukocytes greater than 5500/mm3 could be associated with a better response to the corticotherapy.
Ulrasound scanning can help eliminate the possibility of biliary tract disease in jaundiced and febrile patients.An irregular shrunken liver suggests severe cirrhosis while additional signs such as ascites, varices and splenomegaly.
Liver biopsy
Liver biopsy is necessary to confirm the diagnosis, to assess the extend of liver injury and to provide a prognostic guide.The coagulopathy often associated to severe alcoholic hepatitis may necessitate using the transjugular venous route for performing the biopsy.

In patients with severe disease, the 30-day mortality rate approaches 50% but in all patients with alcoholic hepatitis the overall 30-day mortality rate is about 15%.
The Maddrey's discriminant function following the below formula has the best correlation and the highest positive predictive value to predict the 30-day mortality. Discriminant function: (4,6 X ptothrombin time prolongation in seconds) + bilirubin (mg/dL).Values above 32 indicate severe disease. The prognostic value of this formula has been prospectively confirmed and appears to be the most clinically helpful for therapeutic decisions when severity of illness determines treatment.
Others factors that correlate with poor prognosis include older age, impaired renal function, encephalopathy, and a rise in the white blood cell count in the first 2 weeks of hospitalization.

The most important aspect of treatment is abstinence from alcohol
Mild disease
Patients with mild to moderate disease usually survive this stage of their illness as long as they abstain from alcohol use.
Severe disease
Patients with severe alcoholic hepatitis (Maddrey's score above 32) require active, specific treatment to alter the grim, high short-mortality rate.
As shown in table 2, there have been a number of therapeutic agents that have undergone clinical testing for alcoholic hepatitis. Among all of these therapies, only corticosteroids and total enteral nutrition have clearly shown benefit.

Table 2
Propylthiouaril Colchicine Corticosteroids Insulin/glucagon (intravenous Anabolic steroids) Testosterone OxandroloneTotal enteral nutrition Antioxydants ?
Corticosteroids have been the most controversial therapy in alcoholic hepatitis. More than 40 studies have been conducted to test the effect of this treatment. Recent two meta-analyses of 11 randomized control trials are more in favor of corticosteroid therapy for patients with severe disease and spontaneous hepatic encephalopathy. However steroids seems to have a beneficial effect on short term survival but not on long-term survival. Recent study has shown that enteral nutrition was associated with a better long-term outcome compared with corticosteroids. Actually no single therapy had had universally miraculous success.
Nutritional support
Because patients with alcoholic hepatitis often have protein-calorie malnutrition, nutritional support has been a tempting therapeutic option. Recent data have clearly shown that total enteral nutrition (20-30 kcal/kg/day) is actually the treatment of choice because of the beneficial effect on long-term outcome with a decrease of the infections rate.
Liver transplantation
Orthotopic liver transplantation has been shown to be the chief therapeutic option for patients with end-stage alcoholic liver disease. An abstinence of 3 to 6 months before operation is required to have a low rate of alcohol abuse recidivism after transplantation.

Alcoholic hepatitis is a necrotizing, inflammatory process often leading to cirrhosis or death. The diagnosis of this severe condition necessitates to perform liver biopsy.
The pathogenesis is not fully understood although significant progress has been achieved recently. The prognosis is poor in severe disease when alterations of prothombin time and serum bilirubin levels are marked. Abstinence from alcohol and appropriate total enteral nutrition are probably the most effective current treatment.
There is renewed interest in the use of corticosteroids in severe disease. Orthotopic liver transplantation is appropriate for some patients with end-stage liver disease.