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Thursday, December 18, 2008

A team of eight transplant surgeons in Cleveland Clinic in Ohio, USA, led by reconstructive surgeon Dr. Maria Siemionow, age 58, have successfully performed the first almost total face transplant in the US, and the fourth globally, on a woman so horribly disfigured due to trauma, that cost her an eye. Two weeks ago Dr. Siemionow, in a 23-hour marathon surgery, replaced 80 percent of her face, by transplanting or grafting bone, nerve, blood vessels, muscles and skin harvested from a female donor’s cadaver.

The Clinic surgeons, in Wednesday’s news conference, described the details of the transplant but upon request, the team did not publish her name, age and cause of injury nor the donor’s identity. The patient’s family desired the reason for her transplant to remain confidential. The Los Angeles Times reported that the patient “had no upper jaw, nose, cheeks or lower eyelids and was unable to eat, talk, smile, smell or breathe on her own.” The clinic’s dermatology and plastic surgery chair, Francis Papay, described the nine hours phase of the procedure: “We transferred the skin, all the facial muscles in the upper face and mid-face, the upper lip, all of the nose, most of the sinuses around the nose, the upper jaw including the teeth, the facial nerve.” Thereafter, another team spent three hours sewing the woman’s blood vessels to that of the donor’s face to restore blood circulation, making the graft a success.

The New York Times reported that “three partial face transplants have been performed since 2005, two in France and one in China, all using facial tissue from a dead donor with permission from their families.” “Only the forehead, upper eyelids, lower lip, lower teeth and jaw are hers, the rest of her face comes from a cadaver; she could not eat on her own or breathe without a hole in her windpipe. About 77 square inches of tissue were transplanted from the donor,” it further described the details of the medical marvel. The patient, however, must take lifetime immunosuppressive drugs, also called antirejection drugs, which do not guarantee success. The transplant team said that in case of failure, it would replace the part with a skin graft taken from her own body.

Dr. Bohdan Pomahac, a Brigham and Women’s Hospital surgeon praised the recent medical development. “There are patients who can benefit tremendously from this. It’s great that it happened,” he said.

Leading bioethicist Arthur Caplan of the University of Pennsylvania withheld judgment on the Cleveland transplant amid grave concerns on the post-operation results. “The biggest ethical problem is dealing with failure — if your face rejects. It would be a living hell. If your face is falling off and you can’t eat and you can’t breathe and you’re suffering in a terrible manner that can’t be reversed, you need to put on the table assistance in dying. There are patients who can benefit tremendously from this. It’s great that it happened,” he said.

Dr Alex Clarke, of the Royal Free Hospital had praised the Clinic for its contribution to medicine. “It is a real step forward for people who have severe disfigurement and this operation has been done by a team who have really prepared and worked towards this for a number of years. These transplants have proven that the technical difficulties can be overcome and psychologically the patients are doing well. They have all have reacted positively and have begun to do things they were not able to before. All the things people thought were barriers to this kind of operations have been overcome,” she said.

The first partial face transplant surgery on a living human was performed on Isabelle Dinoire on November 27 2005, when she was 38, by Professor Bernard Devauchelle, assisted by Professor Jean-Michel Dubernard in Amiens, France. Her Labrador dog mauled her in May 2005. A triangle of face tissue including the nose and mouth was taken from a brain-dead female donor and grafted onto the patient. Scientists elsewhere have performed scalp and ear transplants. However, the claim is the first for a mouth and nose transplant. Experts say the mouth and nose are the most difficult parts of the face to transplant.

In 2004, the same Cleveland Clinic, became the first institution to approve this surgery and test it on cadavers. In October 2006, surgeon Peter Butler at London‘s Royal Free Hospital in the UK was given permission by the NHS ethics board to carry out a full face transplant. His team will select four adult patients (children cannot be selected due to concerns over consent), with operations being carried out at six month intervals. In March 2008, the treatment of 30-year-old neurofibromatosis victim Pascal Coler of France ended after having received what his doctors call the worlds first successful full face transplant.

Ethical concerns, psychological impact, problems relating to immunosuppression and consequences of technical failure have prevented teams from performing face transplant operations in the past, even though it has been technically possible to carry out such procedures for years.

Mr Iain Hutchison, of Barts and the London Hospital, warned of several problems with face transplants, such as blood vessels in the donated tissue clotting and immunosuppressants failing or increasing the patient’s risk of cancer. He also pointed out ethical issues with the fact that the procedure requires a “beating heart donor”. The transplant is carried out while the donor is brain dead, but still alive by use of a ventilator.

According to Stephen Wigmore, chair of British Transplantation Society’s ethics committee, it is unknown to what extent facial expressions will function in the long term. He said that it is not certain whether a patient could be left worse off in the case of a face transplant failing.

Mr Michael Earley, a member of the Royal College of Surgeon‘s facial transplantation working party, commented that if successful, the transplant would be “a major breakthrough in facial reconstruction” and “a major step forward for the facially disfigured.”

In Wednesday’s conference, Siemionow said “we know that there are so many patients there in their homes where they are hiding from society because they are afraid to walk to the grocery stores, they are afraid to go the the street.” “Our patient was called names and was humiliated. We very much hope that for this very special group of patients there is a hope that someday they will be able to go comfortably from their houses and enjoy the things we take for granted,” she added.

In response to the medical breakthrough, a British medical group led by Royal Free Hospital’s lead surgeon Dr Peter Butler, said they will finish the world’s first full face transplant within a year. “We hope to make an announcement about a full-face operation in the next 12 months. This latest operation shows how facial transplantation can help a particular group of the most severely facially injured people. These are people who would otherwise live a terrible twilight life, shut away from public gaze,” he said.

Saturday, October 1, 2011

Last week, Nature Genetics carried twin studies into the genetics of bipolar disorder and schizophrenia. This special report examines the month’s research into the illnesses in detail, with Wikinews obtaining comment from experts based in Australia, the United States, and the United Kingdom ahead of the U.S. Mental Illness Awareness Week, which starts tomorrow.

Eleven genetic regions were identified; seven of these were for schizophrenia and five of those were hitherto undiscovered. The parallel studies, conducted separately, examined more than 50,000 people worldwide and identified two genetic loci associated with both diseases.

Little is known about the two illnesses, each of which affects around 1% of people and is treated with strong medication. Bipolar sufferers experience extremes of mood – depression and mania, hence the previous name “manic depression” for the illness. Schizophrenia is associated with hearing voices, chaotic thoughts, and paranoia. There is no known cure.

The latest research examined both the healthy and the afflicted, using computers to scan genomes. Inheritance was thought to be a factor from prior knowledge of the diseases as a familial trait, but the original desire had been to isolate a single faulty gene. Instead it has become apparent that the genetic factors are many; in the case of schizophrenia, at most around 30% of the genetic components are thought to have been identified.

The University of Chicago’s Pablo Gejman, a lead researcher on the schizophrenia study, explained to Wikinews in a telephone interview from Buenos Aires, Argentina that “One of the goals of genetic research is to find druggable targets” – to “find treatments at the root of the problem”.

Whilst noting that there is no guarantee the genetic code identified is druggable, Gejman named calcium-activated neurochemical channels in the brain as candidates for new drugs. The channels were linked to schizophrenia in the study.

Gejman explained that a genetic locus called mir137 “suggests an abnormality of gene regulation.” The diseases are so poorly understood that it is uncertain if they are in fact two components of a single spectrum, or even each comprised of multiple illnesses.

The new and “provocative data” gathered showed the significant loci identified were “not part of the pre-existent hypothesis.” Calling this “interesting”, Gejman added that the team found no evidence that dopamine receptors are involved; current drug treatments target dopamine receptors. The findings are “not related to anything we thought we knew [about schizophrenia],” he told our correspondent.

Quizzed about the possibility variations in the genetic factors involved in expressing the diseases explained the variation seen in symptoms, Gejman was uncertain. “We will have the answer, probably, only when we sequence the whole [human] genome.” He notes that the relationship between genotype and phenotype is unclear, and that “We know very little of the genetic architecture of schizophrenia and” other disorders.At the time the results were published, participating scientist Professor Rodney Scott from the University of Newcastle in Australia said “The strength of this research is in the numbers. The findings are robust and give us a lot of statistical power to identify the genetic determinants of schizophrenia.” Scott told Wikinews that “If any single centre tried to undertake such a study, it would require millions of pounds. Since it was a collection of data from across the world the costs were spread. In this era of financial difficulty it will become increasingly difficult to secure funding for this type of project even though the pay-offs will be significant.”

Gejman expressed similar sentiment. “The research budget is not growing, which makes [funding] difficult,” he said, though he felt the cost “is not prohibitive because of the benefits.” “I think that it was money well invested” and “very well spent for the future,” he said, adding that organisations in Europe and the US were aware of the importance of such research.

Gejman also agreed on reliability – the study is “Very reliable because of the sample size; that should provide robust results… [we] have worked with a much larger sample than before.” Scott told us it was “a highly reliable study” that has the potential to lead to new treatments “in the long run”.

Another point was the two genetic loci identified as common to both – how much support do they lend to the notion the diseases are linked? “Until more information is available it is really only suggestive,” says Scott. “Strong enough to say there may be potentially a common pathway that bifurcates to give rise to two diseases.”

“It is an excellent demonstration,” said Gejman “because you have the same chains that are common to both disorders, in fact not just the same chains but also the same alleles.” He stressed uncertainty in how strong the relationship was, however.

Scott said examining how the variation of genetic factors may translate into varied symptoms being expressed “certainly is a good target for future research”; “It is not known how many genetic factors contribute to either of these diseases but it is likely that not all are necessary to trigger disease.” “New questions will always arise from any major study,” he told our reporter. “Certainly, new questions about bipolar and schizophrenia are now able to be formulated on the basis of the results presented in the two reports.”

These weren’t the only studies to look at the two diseases together in September. The British Medical Journal carried research by a team from the University of Oxford and King’s College London that examined mortality rates in England for schizophrenia and bipolar sufferers. They found both groups continued to suffer higher mortality rates than the general population – whilst these included suicides, three quarters of deaths were down to ailments such a s heart conditions. General death rates dropped from 1999 to 2006, but sufferers below 65 saw their death rate remain stable – and the over-65 saw theirs increase.

“By 2006, the excess risk in these groups had risk to twice the rate of the general population, whereas prior to that it had only been 1.6 times the risk, so it increased by almost 40%,” said Dr Uy Hoang of Oxford. The study looked at every discharged inpatient with a diagnosis of either condition in England in the relevant time.

Hoang said at the time of the research’s release that doctors should devote attention to predicting and preventing physical illness associated with mental disorders. His study comes at a time when the UK has launched a “no health without mental health” strategy which does attempt to screen for physical illnesses coinciding with mental illnesses. The government aims to reduce the death rate of those with mental disorders.

Rodney Scott described this research result to Wikinews as “Possibly” connected to genetic association with other hereditary ailments, such as cardiovascular disease; he told us another possibility is that “The continued raised mortality rates may be associated with the diseases themselves.”

“We believe the NHS [National Health Service] and Department of Health need to do more to support research and service development for people with bipolar disorder,” Wikinews was told by Suzanne Hudson, Chief Executive of London-based British charity MDF The Bipolar Organisation. “The provision of specialist services for bipolar is very limited in the UK and the demand for our services is unprecedented.”

“A genetic test for bipolar would be a useful tool but the science and ethics are very complex,” Hudson told us, referring to the Nature Genetics genetic study. “Just because someone has ‘bipolar genes’ does not mean they might go on to develop it. Family studies of bipolar show that this is a likely outcome of genetics research in this area. Even if it were possible to accurately predict bipolar in this way, questions about how you treat that person are difficult. For example do you start medication that is not necessary at that point in time?”

“Current treatment is not satisfactory” because it does not always work and has “side effects,” Gejman told us. Robert Whitaker, a US medical journalist and book author, told an audience in New Zealand at the end of August that evidence suggests antidepressant drugs may make children and teenagers worse – “You see many become worse and end up with a more severe diagnosis, like bipolar illness,” and the suicide risk may increase.

Whitaker blames commercial interests. “The adult market appeared saturated, and so they began eying children and teenagers. Prior to this, few children and youth were seen as suffering from major depression, and so few were prescribed anti-depressants.”

One possible alternative, raised by a connection between depressive illness and inflammation, is aspirin and similar compounds. “The link between inflammation and mood disorders has been known for sometime and the use of aspirin and other drugs in depression is now becoming more common in the literature,” Hudson says. “Any new treatments for bipolar, which is a very complex and co-morbid illness, has to be a good thing.”

Professor Dr. Michael Berk, chairman of psychiatry at Australia’s Deakin University, recently gave a talk to just this effect. Speaking at this year’s Congress of the European College of Neuropsychopharmacology, held this past month, he also highlighted statins as a treatment. Recognising the link to physical ailments, he told an interviewer “The brain does not exist in isolation, and we need to understand that pathways similar to those that underpin risks for cardiovascular disorders, stroke, and osteoporosis might also underpin the risk for psychiatric disorders, and that other treatments might be helpful.”

Berk also touched upon speed of diagnosis and treatment; “Early interventions can potentially improve the outcome” of bipolar sufferers, he told his audience. MDF The Bipolar Organisation claim an average of ten years is possible before a person is diagnosed. “This clearly is an issue, if we believe that earlier diagnosis and treatment facilitate better outcomes,” Berk told Wikinews. Though he questions the effectiveness of currently-used drugs on advanced bipolar cases, he does not go so far as to say drugs are actively harmful. He told us “it appears that our best treatments work best earlier in the illness course; and that seems to apply to psychotherapy and pharmacotherapy.”

Berk has already performed research using statins which suggests they can form a treatment. He now seeks funding for research involving aspirin. On funding, he tells Wikinews “psychiatric disorders comprise between 16% and 22% of the burden of disability (depending on who measures it), attracts^[sic] just over 6% of the clinical budget at least in Australia and 3% of the research budget. Research as a discretionary spending item is at great risk.”

Berk’s research, in the past, has been funded by companies including GlaxoSmithKline. Hudson told Wikinews this did not concern her charity; in fact, they welcomed it. “We believe it is important pharmaceutical companies continue to invest in the development of new medications for bipolar. This is how it works in all other health specialities and mental health should be no different.”

“There is a need for greater education for mental health professionals and GPs [general practitioners] about bipolar [in the UK],” she told us. “As the national bipolar charity we receive many, many calls and requests from GPs and other health professionals for our leaflets and information sheets which is fantastic. We very much welcome opportunities to work together for the benefit of individuals affected by bipolar.”

Wikinews contacted the UK’s National Institute for Clinical Excellence (NICE) to discuss issues raised in this article, including future treatments, genetic screening, and mortality rates. NICE did not respond.

Might statins and/or aspirin improve treatment – might they be cheaper, perhaps, or safer? “This is an area of research promise,” says Berk, “however it is too early to make any clinical treatment claims; [all] we can say is that this needs to be studied in properly designed trials capable of giving a more definitive answer.” And what of possible explanations for the increased mortality rate observed in England? Should researchers look at whether bipolar influences more than just the brain, or if it is linked to other genetic conditions?

“For sure,” he told us. “There is new evidence that similar pathways contribute to the risk for both medical and psychiatric illness, both in terms of lifestyle factors, and biomarkers of risk.”