Thursday, January 17, 2008

"Micro-Bubbles" Boost Diabetes Gene Therapy Research

Scientists at Baylor University Medical Center in Texas, US, have developed a novel method of delivering an insulin gene into the pancreas of experimental rats in a potential breakthrough in diabetes research. The researchers injected the rats with microscopic spherical shells enclosing a gene that codes for insulin, which is not produced correctly in the pancreas of diabetes sufferers. The team then directed an ultrasonic pulse at the rats' pancreas, which broke the 'bubble' enclosing the new DNA. This method allows the gene to be delivered to a specific location, crucial in diabetes and until this point one of the biggest barriers to gene therapy.
Previous attempts at gene therapy have relied on the use of harmless viruses engineered to carry the healthy gene. These viruses are injected into the animal or person and the harmless virus and the new, desirable, gene become incorporated into the host's DNA. Gene therapy has a controversial history as this method has the potential for a dangerous immune response, thought to be responsible for the death of teenager Jesse Gelsinger in 1999 whilst undergoing gene therapy for a rare liver disorder. As well as the potential for a dangerous immune response this method does not allow the gene to be targeted to a particular location or organ. Pancreatic cells are the only cells in the body which are fine-tuned to release the correct levels of insulin in response to food intake. If other cells in the body were to pick up and start producing insulin the results could be disastrous. Speaking to the New Scientist, Mark Kay, from the Stanford University School of Medicine, explained that 'the results would be willy-nilly - you'd more likely die from hypoglycaemic shock than the high blood sugar levels' that characterise diabetes.
The team at Baylor injected the bubbles - made with a shell of water insoluble molecules - into rats. The bubbles that were initially injected contained an inert circular piece of DNA - known as a plasmid - engineered with a gene that codes for a fluorescent protein marker. The technique, known as 'ultrasound targeted microbubble destruction', involves using ultrasound waves directed at islet cells in the pancreas. These waves break bubbles in nearby blood vessels which consequently release the gene; the waves also break holes in the membranes of adjacent cells creating a passage for the genes to enter through. After breaking the bubbles in the rat pancreases using the directed ultrasound pulse, researchers dissected the animals and found higher levels of fluorescence in the pancreas than in other areas.
In further experiments the researchers injected bubbles containing a plasmid which had the human gene for insulin engineered into it. Again, after bursting the bubbles researchers dissected the rats and found significantly elevated levels of human insulin in the rodents. The animals' blood sugar levels also dropped compared with rats that were used as controls. 'This work shows that genes can be targeted to pancreatic islets in living, adult animals', commented Paul Grayburn, the cardiologist at Baylor who led the study, published in the Proceedings of the National Academy of Sciences. The next big challenge with this therapy will be developing it so that the effect lasts for a long time - currently the protein produced by the new gene can only be detected for around three weeks after treatment.

Wednesday, January 16, 2008

FINDING TRAVEL INSURANCE THAT COVERS PEOPLE WITH MEDICAL CONDITIONS

Dear Friends,
I came across this nugget on the net. I really thought it worthwhile to share this British article with you.

"Last November, the UK's Genetics and Insurance Committee held a meeting on Family History, Genetics and Insurance, which included presentations providing advice to people with a serious medical condition on buying insurance. This article deals with buying travel insurance if you are affected by a genetic condition, or indeed any long-term medical condition. Finding the right travel insurance policy can be more difficult if you have been diagnosed with a serious health condition. This need not be a major worry, as insurance will be available in almost all cases, but you do need to make sure you shop around with the right insurers. People diagnosed with health conditions will, however, find they usually pay more for travel insurance than people with no serious health issues. This is because they typically present insurers with a higher likelihood of making an expensive medical-related claim. Travel insurers are not concerned with your genetic susceptibility to health conditions and will not ask for the results of predictive genetic screening before selling you a policy. But they do need to know if you have an actual diagnosis of illness. Travel insurance is designed principally to help you pay for emergency medical help while abroad, which is by far the most costly risk people typically face when travelling, and the reason you pay more for cover if you present a higher medical risk. The figures below from the Foreign Office website illustrate the typical costs of getting you home to the UK after a medical emergency:
£30-35,000: Air ambulance from East coast of USA
£15-20,000: Ordinary scheduled flight with doctor escort from Australia
£12-16,000: Air ambulance from Canaries
£10-12,000: Air ambulance from Balearics
£3-£6,000: Ordinary scheduled flight, with stretcher and Doctor escort from Mediterranean
£1,200-3,000: Air taxi (light aircraft) from Northern France
So, in spite of the higher cost you can pay if you have an illness, travel insurance is still well worth buying. The costs of emergency help are high in places that do not offer free health care, such as North America, but even in Europe, emergency medical repatriation to the UK can cost thousands.It is also the case that not all insurers are able to provide cover to
people with serious conditions, such as active cancers. This is because they will not have the right experience in underwriting these risks. In these cases, you will need to contact one of the many specialist insurers on the market.
Here are some useful tips on finding insurance if you have a medical condition:
- Don't always rely on the mass-market insurers, or tour operators that sell insurance as part of a package holiday. Some of these won't be able to cover medical conditions, especially very serious ones.
- Go to specialists - more and more insurers have specialist knowledge of medical conditions and can offer you cover. Some companies specifically market to people with pre-existing medical conditions.
- Shop around - insurance policies differ on both cover and price, so compare the quotes you receive to find the best deal.
- If you have any problems trying to find specialist insurers, use a broker.
They can do the work for you. You can contact a broker through the British Insurance Brokers Association, who host a website and a dedicated customer helpline: Telephone: 090 1814 0015; Email: enquiries@biba.org.uk
The most important thing to remember if you have a medical condition is not to leave insurance until the last minute: make it a key part of your travelling plans and shop around with the right providers to get the best deal.
- Sean Worth, UK Association of British Insurers

Tuesday, January 15, 2008

Unknown Sperm Donor Passes Disease to Five Children

Doctors have discovered that a sperm donor in the US has passed on a rare genetic disease to five children born to four couples who used his sperm to conceive. The disease, severe congenital neutropenia (SCN), can be fatal in children if untreated but is so rare that sperm banks do not typically test for it. Even though donors are asked to give full details about their medical and family history, the information they provide would not necessarily ever indicate the presence of the risk, especially if the man had no symptoms of the condition himself or was only a carrier.
Although the provision of fertility treatment is not regulated in the US, guidelines issued by the American Society of Reproductive Medicine (ASRM) state that anonymous gamete donors must provide a family medical history that goes back for at least three generations. The ASRM guidelines also state that full chromosomal screening is not needed where there is a proper family history detailing any potential heritable disorders. Sperm donors are routinely screened for more common genetic disorders, such as cystic fibrosis or sickle cell anaemia, but not for more rare genetic diseases. The cluster of SCN cases was identified by the SCN International Registry and by Dr Laurence Boxer, director of paediatric haematology and oncology at the University of Michigan and an expert on the disease. Although the researchers did not have sperm samples to test, as the clinic had discarded the remainder of the man's sperm, they concluded that the children affected could all be traced back to the sperm of one man because the four couples with affected children all used sperm from the same sperm bank in Michigan, US, and all had the same version of the defective gene. Dr Boxer, who co-authored a report on the findings published in the Journal of Paediatrics, refused to identify the sperm bank by name, or say where the couples treated came from, and stated that it was not known whether the man concerned knew he was a carrier - the sperm bank only reported that the man concerned was 'healthy'. Dr Boxer speculates that as the man was otherwise healthy, he must have had an unusual condition called mosaicism, in which the mutated gene was carried only in his sperm and not in the rest of his body. 'Otherwise he would have been a very sick man', he said.
SCN occurs in only about one in 5 million births - children born with the disease cannot make the type of white blood cell that kills bacteria in the body and, as a result, they are unable to fight infections. The children affected are receiving treatment which helps them to build up their white blood cell production, said Dr Boxer. But he added that they will always have a greater risk of developing leukaemia than other children and all face a 50 per cent chance of passing the condition on to their own children. 'The bottom line is, when you use a sperm donor, you really don't know what you're getting', he said, adding that prospective parents should be advised that screening of donors will not always identify all potential genetic diseases. 'The mothers need to be prepared that there is always an inherent risk of a genetic disorder being transmitted by the donor's sperm', he advised.

Monday, January 14, 2008

Twins Born 16 Years Apart

UK newspapers have reported on the story of 'twin' girls born 16 years apart following IVF treatment. Jane and Alan Davis began IVF treatment in March 1989. Thirty-three eggs were collected, and fertilised with Mr Davis' sperm, producing a number of viable embryos. Three were implanted and 22 others were kept in frozen storage to potentially be used in the future.
Emma Davis, now 16-years old, was born in December 1989. Her sister, Niamh, who began life as an embryo at the same time as Emma, was born in December 2005. According to UK law, IVF embryos can usually only be kept for five years, with the possibility of an extension. Doctors treating the couple decided that their circumstances were so exceptional that they should be granted a special dispensation to keep their frozen embryos in storage for longer. Although siblings have been born up to 21 years apart after the use of frozen sperm, this means that 16 years is now the record for siblings being born from the same batch of IVF embryos.
'We feel incredibly lucky that we've finally been able to complete our family. It's been a long and traumatic journey, but we're so glad we never gave up', said Mrs Davis who has had ten miscarriages, three ectopic pregnancies and lost a third child - conceived from the same batch of IVF embryos. The ectopic pregnancies, which followed after Mrs Davis conceived naturally after the birth of Emma, damaged Mrs Davis' fallopian tubes so badly that she had no chance of conceiving naturally again. After saving money for more IVF treatment, in 2002, the Davises told Emma they wanted to try for another child using an embryo stored since she was conceived: 'We'd told Emma about the unusual circumstances of her birth and she'd simply accepted it', said Mrs Davis, adding 'she was just thrilled at the prospect of a brother or sister'. However, despite getting pregnant, they lost the baby at six months old. A second attempt ended in a miscarriage and doctors told the couple that embryos could not be kept frozen for ever without losing quality.
In April 2005, the couple decided to have one final attempt at IVF. Each time they tried, six embryos were thawed and the best selected for implantation. 'We knew that after this attempt, only three frozen embryos would remain, which might not be enough to keep trying', said Mrs Davis. But this time the pregnancy was uncomplicated. Dr Goswamy, who treated the couple initially at London's Churchill Clinic, and then later at the Harley Street Fertility Centre, said that he believed 16 years is the longest time between siblings born from embryos created at the same time. 'As far as I know, this is a record', he said, adding 'I don't know of any other case, anywhere in the world, where children from the same batch of eggs have been born 16 years apart'.
The Davises are discussing what to do with their three remaining frozen embryos, but are almost certain they will have them destroyed. 'I doubt three embryos is a large enough number to be useful in research', they said. Speaking about her new sister, Emma Davis said that she realises that 'it's very unusual to have a twin sister born 16 years after me'. She added: 'But we're not identical, and I don't really think of her as my twin, more as my baby sister'.
Although theoretically very long term freezing is possible, the normal period for embryo storage in the UK is limited to five years, because of the risks of embryo deterioration. However, this story seems to suggest that longer-term freezing carries few significant dangers. Planer, the company that developed the freezing equipment in which the embryos were stored, said in a press release that Niamh's birth 'is believed to set a new record for viability in the long term'. The previous record was twelve years, when in February 2004 it was reported in that a 39-year old Israeli woman has given birth to twins using frozen embryos created twelve years prior. On that occasion, the embryos had been frozen prior to storage in a controlled rate freezer also made by Planer.
We have a Planer at Rotunda:)

Sunday, January 13, 2008

Three Siblings affected with rare genetic disease

A British couple have spoken of their heartbreak at having had three young sons diagnosed with the same rare terminal genetic condition. Scott and Nicola Smith, from Eyres Monsell, Leicester, have spoken to the press about discovering their sons' incurable brain disorder. Eight-year old Connor, six-year old Callum, and five-year old Jack all have a condition called adrenoleukodystrophy (ALD), sometimes also called Schilder's Disease. The condition, which affects one in every 20,000 boys, attacks the brain and central nervous system, and most of those affected will die before they reach adulthood. Sufferers are unable to produce an enzyme that breaks down saturated, fatty acids in the brain, causing these to accumulate. Eventually, sufferers lose their sight, hearing and the ability to walk or talk. Current treatments include bone marrow transplants and a dietary fat known as Lorenzo's Oil, also the name of a feature film about a boy suffering from ALD. The film tells the real-life story of Augusto Odone, who developed the oil as a treatment for his son, Lorenzo.
Mrs Smith recently found out that she was a carrier for ALD. The disease is caused by a genetic abnormality involving the X chromosome and is carried by about one in 14,000 women. But by then, she said that she and her husband Scott had already started to see the signs in Callum. Callum was the first to be diagnosed, only last month and, following tests on the other boys, it was discovered that they both were also affected. 'We can't believe this is happening', said Mrs Smith, adding 'it's a nightmare'. She went on to say that 'we always knew there was a chance Connor and Jack would have it, but we prayed and hoped they would escape it'. At present, all three boys appear normal, but doctors say Callum is already showing signs of brain damage.
Dr Jayaprakash Gosalakkal, the consultant paediatric neurologist treating the brothers at Leicester Royal Infirmary, said that it is almost unheard of to have three sufferers of ALD in one family. The only other case where the disease affected more than two boys in the same family was in China where four siblings were diagnosed with the condition, he said. He added that doctors 'are exploring the possibility of bone marrow transplants and also the possibility of stem cell treatment. The investigation is still in its very early stages'. 'I really didn't know how to break it to the mother', he said, adding 'I saw their reaction when I told them about the first son, Callum. Telling them was one of the most awful things I have ever had to do'.

Saturday, January 12, 2008

Placenta Previa linked to ART

Researchers at St Olav's University Hospital in Trondheim, Norway, have discovered a link between assisted reproduction and an increased risk of placenta previa - a dangerous complication of pregnancy where the placenta covers all or part of the cervix. The condition normally affects around three in 1000 births, but with a single IVF or ICSI (intracytoplasmic sperm injection) conception the risk raises to 16 in 1000. The researchers also examined women who had one pregnancy conceived naturally and one conceived using assisted reproduction (ART), in this case the risk rose from around seven in 1000 for two natural conceptions to 20 in 1000 for one ART and one natural; it did not make a difference which pregnancy was through assisted reproduction. This helps to rule out the possibility that there was some maternal factor in the single ART pregnancies which could cloud the findings.
The study, published in Human Reproduction, looked at more than 845,000 cases between 1988 and 2002, and was designed to correct for factors such as maternal age. The underlying reasons for the increased risk are not clear although the team postulate that the position in which the embryos are placed into the womb in ART may be a factor. There is research that suggests conception rates are higher when the embryo is inserted lower down in the uterus - this is also thought to reduce the risk of ectopic pregnancy. The team are now calling on fertility clinics to record this extra data. Dr Liv Bente Romundstad, leader of the study, said 'we now routinely do this, but we need other centres worldwide to do this as well'. She added: 'Although the risk of placenta previa is considerably higher with ART it is still quite rare, which means it will probably take several thousand pregnancies to get sufficient data to be able to make any definite recommendations about clinical practice'.
In the paper the researchers suggest that assisted reproduction techniques may induce uterine contractions after stimulation of the cervix, this may then lead to more embryos implanting low-down. If the placenta covers the whole of the cervix then the baby must be delivered by caesarean section. There is also an increased risk of bleeding or hemorrhage as the placenta is stretched during the final stages of pregnancy.
Dr Romundstad said that 'regardless of whether it was the first or second pregnancy that was conceived through assisted reproductive technology, we found a nearly threefold higher risk of placenta previa', adding that 'this suggests a substantial proportion of the extra risk may be attributable directly to factors relating to the reproduction technology'. In the light of the findings, Dr Mark Hamilton, chairman of the British Fertility Society, said that 'patients who are considering IVF treatment should discuss concerns with their gynecologist in advance of treatment and those who are pregnant might want to discuss this with their obstetrician'.

Friday, January 11, 2008

Uphill Metro




Here is something you don’t see everyday (unless you live in Israel of course). In the city of Haifa in Israel you can find the only subway system in Israel - and it’s a pretty complicated one since it is capable of going uphill. I like it maybe because I live a sheltered life but I’ve never been more surprised by a public transport system than when I came across this little beauty. It’s called the Carmelit, it runs underground in the citry of Haifa, Israel and it’s the country’s only subway system. Due to the city being located on the side of Mount Carmel, the entire single track ‘funicular’ system has been designed to accommodate the incline, hence the strange stepped stations and diagonal trains. I’m told they’re more common at ski resorts which would maybe explain why I’ve never seen one before.

Either way, it’s quirky and it’s brilliant.

Because much of Haifa is built on top of the Mt Carmel, the Carmelit (named after this mountain) is an underground funicular that goes up and down the mountain. The altitude difference between the first and last stations is 274 meters.) Carmelit cars have a slanted design, with steps within each car and on the station platform. Since the gradient varies along the route, the floor of each car is never quite level, and slopes slightly "uphill" or "downhill" depending on the location. The Carmelit is one of the smallest subways in the world, having only four cars, six stations and a single tunnel 1800 meters long. The four cars operate as two two-car trains, which run on single track with a short double-track section to allow trains to cross.
It is not the smallest subway in the world - the Istanbul Tünel, with two stations and 573 meters long, is smaller. However, since Istanbul also has a newer and bigger (though separate) subway system, the Carmelit is the smallest subway system in the world.