The Tribune, Chandigarh, India

Living after death
By Dr Kamal Sud and Prof Vinay Sakhuja

Over the past three decades, organ transplantation has evolved from just an experiment in human biology to an accepted form of treatment for patients suffering from end-stage organ failures. Tissue transplantation has also undergone similar advances. It has become an accepted practice in areas as diverse as orthopaedics and ophthalmology. Newer drugs and improved skills of health professionals are making more and more transplants successful.

The ability of transplant centres to offer this effective treatment is limited by the availability of donor organs and tissues and many people are still dying or are crippled owing to the lack of possible donors. Today, in the more advanced countries, it is possible to transplant different organs and tissues, including corneas, kidneys, heart, liver, lungs, pancreas, intestines, skin, bone marrow, bones and cartilage from a single organ donor.

While tissues such as the cornea, bone and cartilage can be removed within hours of a cardiac arrest and still be suitable for transplantation, most other organs require a persistent blood circulation to be viable and to be of any use to the recipient after transplantation. It is in this context the concept of brainstem death has been evolved to define death before the heart stops beating. If organs could be removed from these individuals with brainstem death and a beating heart, they could be transplanted into the recipients suffering from various organ failures.

It is quite difficult to define "death". Unless one defines death, the decision that a person is dead cannot be verified scientifically. This is because the available technical data cannot always answer a purely conceptual question.

Whereas the functions of the lungs and the heart can be taken over by machines for a finite extent of time, those of the brain cannot.

An individual can, therefore, be dead only when his brain is dead. Death can be defined as an irreversible loss of capacity for consciousness combined with the irreversible loss of capacity to breathe (and hence the ability to sustain a spontaneous heart beat). In such a situation even if ventilation is assisted by machines, the heart would stop beating in a matter of a few hours or days and the individual will be considered to be "dead" as one usually perceives death.

Death, thus conceived, can arise from primary catastrophes within the head, or it can be a consequence of an event elsewhere, like a cardiac arrest. Such a circulatory arrest will prove lethal if it lasts long enough for the brain stem to die. Therefore, all death in this perspective is brain stem death — is all the key functions that define a human being to be alive, i.e, the capacity to be conscious and the capacity to breathe (and in turn sustain heart beat) are subserved by the brain stem.

We can now be more specific about the parts of the brain which relate to these important functions. The capacity for consciousness and the capacity to breathe spontaneously are both functions of the brain stem. The capacity for consciousness is an upper brain stem function and a small lesion affecting this part of the brain produces permanent coma. The capacity of consciousness is not the same as the content of consciouness, which is a function of the cerebral hemispheres. However, the former is an essential precondition of the latter. If there is no capacity for consciousness, there can be no meaningful or integrated activity of the cerebral hemispheres, no cognitive life, no thoughts or feelings and no social interaction with the environment. The capacity for consciousness is, perhaps, the nearest we can get scientifically to the notion of the "soul". The capacity to breathe spontaneously is a lower brain stem function. Alone, it cannot imply death, because a conscious individual, with the irreversible arrest of the ventilatory functions, can be sustained on a mechanical ventilator. It is pointless to maintain the ventilator and circulatory functions by artificial means when there is no longer a working brain stem. The individual can be considered to be dead if the brain has irreversibly and permanently ceased to function. Such an individual will always have a cardiac arrest despite all resuscitatory measures in a period of hours to a few days. More than 2000 patients with brain stem death have been reported and none have survived for more than a few days.

Modern technology, in its attempt to save human lives, has created numerous problems and the concept of brain death is one of them. It has thrown up clinical, conceptual and ethical questions. Moreover, arguments over brain death have highlighted the tensions between science and ethics; (should one continue to give artificial respiration until such time as the heart stops beating?); between physicians and the law (how will a hostile lawyer react to all this?). With these problems in mind and in order to facilitate organ and tissue donation after death and to prevent commercial dealings in human organs. Parliament passed the Transplantation of Human Organs Act in 1994. The Act laid down rules on giving authorisation for the removal of organs and also issued regulations for hospitals for defining brain stem death and for conducting transplantation. Under this Act, the authority or consent for the removal of organs can be given by any person any time before his or her death in writing and in the presence of two or more witnesses. The near relative, in possession of the dead body, will then allow the doctor to remove organs unless the near relative has any reason to believe that the consent had subsequently been revoked.

In case there was no written consent (given before death) the relative in possession of the body can authorise the doctors to remove organs if this relative believes that no objection was expressed by the deceased before his or her death.

Simply but, therefore, any person can authorise his or her near-relative in writing or even verbally, to allow or disallow the removal of organs for transplantation after his or her death. In case there has been no such authority, the near relative can still allow the removal of organs provided he believes that the deceased did not express his wishes to the contrary when he or she was alive.

To certify brain stem death, the Act has laid very stringent criteria. The patient should be suffering from a known and irreparable structural brain lesion and all known reversible causes of coma (including drug intoxication and hypothermia) must be excluded even before he is eligible to be considered for organ donation.

Brain stem death is certified after the patient is thoroughly examined at least two times at an interval of at least six hours by a team of doctors consisting of (i) an approved neurologist or a neurosurgeon (ii) the treating doctor under whose care the patient is admitted (iii) an independent specialist nominated by the Medical Superintendent from a list of names approved by the appropriate authority set up under the Act and (iv) the Medical Superintendent of the hospital. No member of the transplant team is part of this committee, lest he or she could influence the decision on certifying brain death. Once brain stem death is certified, all supportive care is continued as was being done before and the process of identification of the possible recipients of the organs is begun and preparations made for the surgery.

After the surgery, the body is handed over to the near relatives immediately, unless it is required for an autopsy for medico-legal purposes. The consent for organ removal or donation can be limited to one or more organs according to the wishes of the person pledging the organs or the near-relative acting on his or her behalf after death.

Unfortunately, the Transplantation of Human Organs Act has had a very limited impact on patients with end-stage organ failures in the six years since its inception. Although reports of the first heart or liver transplants in the country have made the headlines and are noteworthy personal surgical feats, these procedures have yet to make a significant impact on the vast majority of the patients with end-stage liver or heart failures who are still dying without being offered such an option. Among the kidney transplants that are performed routinely at the PGI, Chandigarh, relatives of only three brain stem dead patients have agreed for organ donation in six years and this has helped save the lives of six patients with kidney failure. However, an average of 30 to 40 patients are on dialysis at any given time waiting for a kidney transplant in the city, many of whom actually die before receiving a transplant.

Even though organ transplantation is expensive, every citizen of our country is within his right to demand the best possible treatment.

One can see, however, why it is not a priority area for the government of a poor and developing country like ours where expenditure on health is a very small percentage of the total budget and where these meagre resources are spent on the prevention and treatment of communicable diseases which affect a much larger population and require relatively cheaper forms of treatment.

But this should not imply that organ transplantation is not offered to those who can afford it. In a largely literate population like ours, one could see more people willing to become organ donors in the hope that they could save some lives even after their death and continue to live in someone else's body. For this to happen, a social movement is required to educate the public about brain stem death and organ donation and that is the objective of the present article. It is the authors' belief that by generating public awareness and a debate on the concept of brain stem death, more and more people will be brought forward as organ donors. We see no reason why transplants of organs other than kidneys and corneas cannot be routinely performed when surgical expertise is available.

Dr Sakhuja is the Professor and Head of the Nephrology Department at the PGI, Chandigarh. Dr Sud is an Assistant Professor.

Depression among women-II
Better half: bitter truth
By Dr Rajeev Gupta

It has been a well-documented fact that in developing countries women are given a low priority in providing the citizens with medical help. Since the presentation of depression is predominantly physical or somatic, depressed patients tend to land up in medical and surgical clinics and their depression remains unidentified and untreated for long periods. The common symptoms experienced by the patients are: (physical) — fatigue, tiredness, body-aches, the loss of energy, the loss of appetite, headache, low drive, and the loss of the interest in work and social activities. Family doctors consider them as suffering from medical disease and keep on pumping in them all kinds of pain-killers and tonics. The underlying depression remains missed in the majority of such cases, which may lead to completely avoidable pain and suffering.

In the developing countries, including India, there is a poor network of mental health professionals. This adds to the chronicity of the problem. Most of the psychiatric services are in the private sector. These are predominantly concentrated in urban areas and are beyond the reach of the most of the psychiatric patients. In many parts of the country, illiteracy, and ignorance of the disease, continue to play a predominant role in determining the course of the ailment.

The problems of women are often ignored: It has been my experience that many of the physical and psychological complaints of the female patients are not taken seriously and are ignored by their families, with the result that the underlying depression remains unidentified and untreated. These patients continue to suffer from the pain and misery of depression.

It is a common observation that women are more tolerant to physical and psychic pain than men which further delays their contact with the health professionals. The ability to tolerate suffering in females is deep-rooted in our culture. Women are trained to be tolerant and submissive.

In my clinical practice, I observe quite frequently that many newly married women never disclose their serious problems in their in-laws house.

The Indian woman is a great stress-absorber. Every kind of stress, particularly that which is related to inter-personal relations, gets directed at her and, like a strong warrior, she is supposed to take these in her stride. Such a prolonged state of stressed life becomes a precursor to the future state of helplessness and depression. It appears that many women keep on simmering with unpleasant feelings and emotions for years which find almost no outlet for their expression.

The management of depression: It depends upon the stage of depression. Patients with mild depression are able to go on with their work and other social and family responsibilities. If they are able to increase their physical and social activities, they can come out of depression.

A change of place and interaction with their friends colleagues and relatives may help them feel better.

When symptoms like disturbed sleep, poor appetite, sadness, negative feelings, anxiety and fear try to overpower them, they feel that depressive symptoms are affecting their occupational and personal capabilities. And, therefore, they should visit a family physician, a medical specialist or a psychiatrist for professional help! Such patients have moderate depression.

Those, who have the disease —quite severe in nature, — feel completely knocked down. They remain confined to the four walls of their houses and may keep on crying the whole day. They are even inclined to committing suicide. Such cases need immediate psychiatric help.

Patients with moderate to severe depression are overpowered by the manifestations of the disease. They must get advice from a physician or a psychiatrist. Untreated depression may disrupt their personal, social and occupational life.

It is important to boost the morale of such women and help them enhance their self-esteem and social status. Mental health professionals are frequently unable to cope with the magnitude of the fast-growing problem. They have a challenging task before them.

(Concluded)

The author is a Ludhiana-based psychiatrist. He maintains a health site, www.meditrackindia.com, for the needy.

Paid to drink poison
From Gavin Evans in London

To a cash-strapped student or an unemployed job-seeker, the offer of several hundred pounds for swallowing a glass of "fruit juice" or an innocent-looking capsule is hard to refuse — especially when assurances are given that the process is ethically sound, independently monitored and risk-free.

Robert Lonie is one of many young people in Edinburgh volunteering for such medical experiments — "a regular source of income for many of us students."

When Lonie was invited by the Edinburgh-based Inveresk Medical Research Laboratory to test azinphosmethyl for the German drugs giant Bayer for a fee of £ 460, he was assured the project had been "approved by an ethics committee, and that the drugs had been proved to be harmless to humans."

In the event, Lonie could not take part in the test because he was on other medication, but he asked his mother — a science teacher — to find out more about azinphosmethyl.

"She told me it was a potentially lethal organophosphate pesticide, not registered for use in the UK. To say I was angry would be an understatement. I felt they had asked me to swallow poison without explaining what it was and what risks were involved."

Lonie later discovered that azinphosmethyl belongs to a group of highly toxic insecticides, which target a blood enzyme essential to the nervous system. A student he subsequently met had suffered from pesticide poisoning after similar testing carried out by another company.

Bayer insists its tests are perfectly safe and carried out under strict international ethical and scientific guidelines. Spokesman Michael George says the company has had "no reports of anyone suffering from adverse side-effects."

Hundreds of British students, unemployed people and immigrants are eagerly ingesting unlicensed chemicals for money. An advertisement in The Big Issue, a weekly magazine for homeless people, offers £ 100 per day for "taking part in medical trials all approved by ethical review boards."

In 1985 two British student volunteers died after participating in trials. Although some trials are for drugs that might be of benefit to medical science, an increasing number involve potentially harmful organophosphate pesticides. Bayer is one of a number of manufacturers testing pesticides in Britain.

Testing is prompted by a United States food safety legislation aimed at protecting children from harmful pesticides. To obtain licences from the US Food and Drugs Administration, manufacturers need to test their products on large numbers of humans. Britain has emerged as an international centre for testing, due to its relative lack of controls and independent safeguards.

MP Paul Tyler, who heads a 90-strong Organophosphate Group in Parliament, suspects the country is seen as a "soft touch" by US and European companies, and claims "they are getting away with tests here they wouldn't have dared to try at home."

Tyler has questioned the government on the flimsy ethical controls on private drug companies and laboratories, and says that "in effect, they are their own policemen.. There is no outside monitoring. Instead, they are monitored by the companies themselves, which set up their own ethical review boards."

Bayer's Michael George insists that Inveresk is used for test programmes because "they have an excellent international reputation."

But claims by manufacturers that the tests present no danger to volunteers are coming increasingly under fire, and a number of their safety assurances have subsequently been disproved.

The Organophosphate Information Network, a voluntary organisation set up to raise public awareness, says it has reports of 700 people suffering chronic symptoms as a result of occupational exposure to pesticides. Network coordinator Elizabeth Sigmund points out that "even low-level exposure can result in damage to the central nervous system leading to clinical depression, headaches and short-term memory loss."

Sigmund says the organophosphate involved in Lonie's case was the first-ever human trial for azinphosmethyl. But her advice "to any would-be human guinea pig" is "say no to any form of organophosphate — no matter how financially desperate you are. Even at low doses, the direct ingestion of any organophosphate carries a high risk, and the damage is cumulative."

Such concerns are backed by a 10-year survey of British clinical drug trials, which revealed serious flaws in safety procedures. In one-third of the 226 trials sampled, the report showed "significant under reporting" of side-effects. Forty-three per cent of patients were not given clear instructions, and in over half the trials there were doubts about proper storage of the drugs.

Dr Wendy Bohaychuk, Editor of Clinical Research Focus, the journal that published the survey results, comments: "I would never go into a clinical study myself, and I would certainly try to discourage anyone in my family from doing so."

Denise Horn of the Ministry of Agriculture agrees that "people should think twice about using organophosphates," but points out: "This is contract research and is therefore covered by the international protocols and the guidelines of the Royal College of Physicians."

In practice, this means "it is up to the client to satisfy itself that ethical conditions are being complied with, and there is no government control on the process."

The Inveresk Laboratory, however, says in a statement that "trials are conducted under appropriate medical and nursing supervision, an independent committee advises on the ethical aspects of the trials," and that "all relevant information" is given to the ethics review committee and those taking part.

Such assurances are not enough for Paul Tyler. "We know that organophosphate-based products are extremely dangerous to human health, and there are suspicions that their use may be related to the spread of BSE (mad cow disease) in cattle, but many of these human guinea pigs are simply not being given sufficient information about the chemicals concerned." — Gemini