Gamete cryopreservation could help improve the fertility of men whose spermatozoa show a high level of prefreeze DNA fragmentation, study findings indicate.
Laura Thomson (Fertility First, Hurstville, Australia) and co-authors note potential cryoinjury of sperm from subfertile men is an issue of primary concern “considering that subfertile men form a very large proportion of the men requiring semen cryopreservation.”
The findings were observed during a study comparing different cryoprotectants used to store spermatozoa for fertility treatment. The study involved 320 men who presented for fertility investigations and provided semen samples.
Post-thaw sperm DNA integrity was unaffected by the type of cryoprotectant used during freezing, but showed a significant, negative correlation with the prefreeze level of DNA fragmentation. Among men with prefreeze sperm DNA fragmentation levels within the normal range, 89 percent showed an increase in fragmentation post-thaw. Conversely, 64 percent of those with very high levels of prefreeze fragmentation showed a decrease in fragmentation post-thaw.
The authors suggest that the result “gives rise to a possible novel method of reducing fragmentation in sperm used for assisted reproductive technology treatment cycles, in some cases without the need for invasive and expensive testicular sperm retrievals.”
Friday, October 31, 2008
Thursday, October 30, 2008
Cell phone risk to sperm supported
An in vitro comparison study has strengthened concerns that electromagnetic radiation from cell phones impairs male fertility.
Ashok Agarwal (Cleveland Clinic, Ohio, USA) and colleagues set out to validate the implications of recent epidemiologic studies, which reported reductions in sperm motility, morphology, and viability associated with cell phone exposure.
They studied neat semen samples from 23 normal healthy donors and nine infertility patients. They divided the samples into two aliquots and exposed one of each sample to radiation from cell phones in talk mode, leaving the second aliquot unexposed to serve as controls.
Analysis revealed significantly lower sperm motility and sperm viability in aliquots of exposed compared with unexposed sperm (49 vs 52 percent and 52 vs 59 percent, respectively).
Levels of reactive oxygen species were also significantly higher in samples of exposed compared with unexposed sperm (0.11 vs 0.06 x106 cpm/20 million sperm), Agarwal et al report.
Total antioxidant capacity and levels of DNA damage did not differ significantly between the two groups.
“We speculate that keeping the cell phone in a trouser pocket in talk mode may negatively affect spermatozoa and impair male fertility,” the researchers conclude.
Source: Fertility and Sterility 2008; Advance online publication
Ashok Agarwal (Cleveland Clinic, Ohio, USA) and colleagues set out to validate the implications of recent epidemiologic studies, which reported reductions in sperm motility, morphology, and viability associated with cell phone exposure.
They studied neat semen samples from 23 normal healthy donors and nine infertility patients. They divided the samples into two aliquots and exposed one of each sample to radiation from cell phones in talk mode, leaving the second aliquot unexposed to serve as controls.
Analysis revealed significantly lower sperm motility and sperm viability in aliquots of exposed compared with unexposed sperm (49 vs 52 percent and 52 vs 59 percent, respectively).
Levels of reactive oxygen species were also significantly higher in samples of exposed compared with unexposed sperm (0.11 vs 0.06 x106 cpm/20 million sperm), Agarwal et al report.
Total antioxidant capacity and levels of DNA damage did not differ significantly between the two groups.
“We speculate that keeping the cell phone in a trouser pocket in talk mode may negatively affect spermatozoa and impair male fertility,” the researchers conclude.
Source: Fertility and Sterility 2008; Advance online publication
Wednesday, October 29, 2008
Gender selection: From diet to chromosomes
A link between what women eat before conception and the sex of their baby has been found in research from the Universities of Exeter and Oxford in the UK.
The results of their study show a clear association between a high energy intake before conception and the birth of sons. As well as consuming more calories, women who had sons were more likely to have eaten a higher quantity and wider range of nutrients, such as potassium, calcium, and vitamins C, E, and B12 than women who had girls. There was also a strong correlation between women who ate breakfast cereals and the birth of male children.
The study's lead author, Dr Fiona Mathews from the University of Exeter, said: "Potentially, males of most species can father more offspring than females, but this can be strongly influenced by the size or social status of the male, with poor quality males failing to breed at all. Females, on the other hand, reproduce more consistently. If a mother has plentiful resources then it can make sense to invest in producing a son because he is likely to produce more grandchildren than would a daughter. However, in leaner times having a daughter is a safer bet."
The study was performed in 740 nulliparous women with normal singleton pregnancies who kept a prospective food diary of their diet in early pregnancy and gave a retrospective report of their usual diet in the year prior to conception. Results showed that 56 percent of women in the highest third of preconceptional energy intake bore boys, compared with 45 percent of those in the lowest third. However, intakes during pregnancy were not associated with any gender differences, suggesting, say the authors, that the fetus does not manipulate maternal diet.
The results, the authors add, are relevant for two reasons: first, that changes in dietary habits (skipping breakfast, for example) may explain the falling proportion of male births in industrialized countries; and second, as more evidence in the debate about gender selection in fertility treatment. The latter represents a continuing ethical issue for those involved in assisted reproduction.
Gender selection in IVF has been rarely (and controversially) described for the purposes of "family balancing" and more routinely as a medical indication for couples at risk for passing on a sex-linked single gene defect to their offspring. Indeed, the first reported pregnancies following pre-implantation genetic diagnosis (PGD), from the Hammersmith Hospital in London in 1990, were in couples at risk of transmitting recessive X chromosome-linked diseases to their children. That risk was removed by the chromosomal detection of gender in each embryo (then done by polymerase chain reaction) and the transfer of only "female" embryos.
The latest report from the PGD Consortium of ESHRE (European Society of Human Reproduction and Embryology), the only group today collecting data on PGD, shows that, during the 6 years prior to the latest analysis (for 2004, with pregnancies into 2005), there were a total of 703 cycles of sexing for X-linked disease performed among the reporting centers. In 2004 alone, 113 cycles were reported, nearly all using fluorescent in situ hybridization (FISH) to identify gender.
The Consortium's 2004 analysis showed that, of the embryos successfully biopsied, 93 percent (564/608) gave a diagnostic result, of which only 32 percent (183/564) were transferable (female); only 67 percent of the started cycles (76/113) reached embryo transfer. A positive heartbeat was found in 20 cycles (18 percent), giving an implantation rate of 17 percent (20/120), rates similar to those found in previous data collections.
The same dataset also shows that, in 2004, 79 cycles of PGD were preformed for "social sexing," most of which were in couples requesting a male embryo. However, social sex selection remains controversial and the debate about its application continues. Sex selection for non-medical reasons is still prohibited in India, Europe and Australia and patients having any type of PGD are not permitted to choose embryos on the basis of gender.
The results of their study show a clear association between a high energy intake before conception and the birth of sons. As well as consuming more calories, women who had sons were more likely to have eaten a higher quantity and wider range of nutrients, such as potassium, calcium, and vitamins C, E, and B12 than women who had girls. There was also a strong correlation between women who ate breakfast cereals and the birth of male children.
The study's lead author, Dr Fiona Mathews from the University of Exeter, said: "Potentially, males of most species can father more offspring than females, but this can be strongly influenced by the size or social status of the male, with poor quality males failing to breed at all. Females, on the other hand, reproduce more consistently. If a mother has plentiful resources then it can make sense to invest in producing a son because he is likely to produce more grandchildren than would a daughter. However, in leaner times having a daughter is a safer bet."
The study was performed in 740 nulliparous women with normal singleton pregnancies who kept a prospective food diary of their diet in early pregnancy and gave a retrospective report of their usual diet in the year prior to conception. Results showed that 56 percent of women in the highest third of preconceptional energy intake bore boys, compared with 45 percent of those in the lowest third. However, intakes during pregnancy were not associated with any gender differences, suggesting, say the authors, that the fetus does not manipulate maternal diet.
The results, the authors add, are relevant for two reasons: first, that changes in dietary habits (skipping breakfast, for example) may explain the falling proportion of male births in industrialized countries; and second, as more evidence in the debate about gender selection in fertility treatment. The latter represents a continuing ethical issue for those involved in assisted reproduction.
Gender selection in IVF has been rarely (and controversially) described for the purposes of "family balancing" and more routinely as a medical indication for couples at risk for passing on a sex-linked single gene defect to their offspring. Indeed, the first reported pregnancies following pre-implantation genetic diagnosis (PGD), from the Hammersmith Hospital in London in 1990, were in couples at risk of transmitting recessive X chromosome-linked diseases to their children. That risk was removed by the chromosomal detection of gender in each embryo (then done by polymerase chain reaction) and the transfer of only "female" embryos.
The latest report from the PGD Consortium of ESHRE (European Society of Human Reproduction and Embryology), the only group today collecting data on PGD, shows that, during the 6 years prior to the latest analysis (for 2004, with pregnancies into 2005), there were a total of 703 cycles of sexing for X-linked disease performed among the reporting centers. In 2004 alone, 113 cycles were reported, nearly all using fluorescent in situ hybridization (FISH) to identify gender.
The Consortium's 2004 analysis showed that, of the embryos successfully biopsied, 93 percent (564/608) gave a diagnostic result, of which only 32 percent (183/564) were transferable (female); only 67 percent of the started cycles (76/113) reached embryo transfer. A positive heartbeat was found in 20 cycles (18 percent), giving an implantation rate of 17 percent (20/120), rates similar to those found in previous data collections.
The same dataset also shows that, in 2004, 79 cycles of PGD were preformed for "social sexing," most of which were in couples requesting a male embryo. However, social sex selection remains controversial and the debate about its application continues. Sex selection for non-medical reasons is still prohibited in India, Europe and Australia and patients having any type of PGD are not permitted to choose embryos on the basis of gender.
Tuesday, October 28, 2008
Embarassing Medical Moments
A man comes into the ER and yells, 'My wife's going to have her baby in the cab!'
I grabbed my stuff, rushed out to the cab, lifted the lady's dress, and began to take off her underwear. Suddenly, I noticed that there were several cabs -- and I was in the wrong one.
Submitted by Dr. Mark MacDonald, San Antonio , TX
At the beginning of my shift, I placed a stethoscope on an elderly and slightly deaf female patient's anterior chest wall. 'Big breaths,' I instructed. 'Yes, they used to be,' replied the patient.
Submitted by Dr. Richard Byrnes, Seattle , WA
One day I had to be the bearer of bad news when I told a wife that her husband had died of a massive myocardial infarct. Not more than five minutes later, I heard her reporting to the rest of the family that he had died of a 'massive internal fart.'
Submitted by Dr. Susan Steinberg
During a patient's two week follow-up appointment with his cardiologist, he informed me, his doctor, that he was having trouble with one of his medications. 'Which one?' I asked. 'The patch, the nurse told me to put on a new one every six hours, and now I'm running out of places to put it!' I had him quickly undress, and discovered what I hoped I wouldn't see. Yes, the man had over fifty patches on his body!
Now, the instructions include removal of the old patch before applying a
new one.
Submitted by Dr. Rebecca St. Clair, Norfolk , VA.
While acquainting myself with a new elderly patient, I asked, 'How long have you been bedridden?' After a look of complete confusion, she answered...'Why, not for about twenty years -- when my husband was alive.'
Submitted by Dr Steven Swanson, Corvallis , OR
I was caring for a woman and asked, 'So, how's your breakfast this morning?' 'It's very good, except for the Kentucky Jelly. I can't seem to get used to the taste,' the patient replied. I then asked to see the jelly, and the woman produced a foil packet labeled 'KY Jelly.'
Submitted by Dr. Leonard Kransdorf, Detroit , MI
A nurse was on duty in the emergency room when a young woman with purple hair styled into a punk rocker mohawk, sporting a variety of tattoos, and wearing strange clothing, entered. It was quickly determined that the patient had acute appendicitis, so she was scheduled for immediate surgery. When she was completely disrobed on the operating table, the staff noticed that her pubic hair had been dyed green, and above it there was a tattoo that read, 'Keep off the grass.' Once the surgery was completed, the surgeon wrote a short note on the patient's
dressing, which said, 'Sorry, had to mow the lawn.'
Submitted by RN, no name
AND FINALLY!!!...
As a new, young MD doing his residency in OB , I was quite embarrassed when performing female pelvic exams. To cover my embarrassment, I had unconsciously formed a habit of whistling softly.
The middle-aged lady upon whom I was performing this exam suddenly burst out laughing and further embarrassing me. I looked up from my work and sheepishly said, 'I'm sorry. Was I tickling you?' She replied, 'No doctor, but the song you were whistling was, 'I wish I was an Oscar Meyer Wiener.'
Doctor wouldn't submit his name (Can't blame him!)
I grabbed my stuff, rushed out to the cab, lifted the lady's dress, and began to take off her underwear. Suddenly, I noticed that there were several cabs -- and I was in the wrong one.
Submitted by Dr. Mark MacDonald, San Antonio , TX
At the beginning of my shift, I placed a stethoscope on an elderly and slightly deaf female patient's anterior chest wall. 'Big breaths,' I instructed. 'Yes, they used to be,' replied the patient.
Submitted by Dr. Richard Byrnes, Seattle , WA
One day I had to be the bearer of bad news when I told a wife that her husband had died of a massive myocardial infarct. Not more than five minutes later, I heard her reporting to the rest of the family that he had died of a 'massive internal fart.'
Submitted by Dr. Susan Steinberg
During a patient's two week follow-up appointment with his cardiologist, he informed me, his doctor, that he was having trouble with one of his medications. 'Which one?' I asked. 'The patch, the nurse told me to put on a new one every six hours, and now I'm running out of places to put it!' I had him quickly undress, and discovered what I hoped I wouldn't see. Yes, the man had over fifty patches on his body!
Now, the instructions include removal of the old patch before applying a
new one.
Submitted by Dr. Rebecca St. Clair, Norfolk , VA.
While acquainting myself with a new elderly patient, I asked, 'How long have you been bedridden?' After a look of complete confusion, she answered...'Why, not for about twenty years -- when my husband was alive.'
Submitted by Dr Steven Swanson, Corvallis , OR
I was caring for a woman and asked, 'So, how's your breakfast this morning?' 'It's very good, except for the Kentucky Jelly. I can't seem to get used to the taste,' the patient replied. I then asked to see the jelly, and the woman produced a foil packet labeled 'KY Jelly.'
Submitted by Dr. Leonard Kransdorf, Detroit , MI
A nurse was on duty in the emergency room when a young woman with purple hair styled into a punk rocker mohawk, sporting a variety of tattoos, and wearing strange clothing, entered. It was quickly determined that the patient had acute appendicitis, so she was scheduled for immediate surgery. When she was completely disrobed on the operating table, the staff noticed that her pubic hair had been dyed green, and above it there was a tattoo that read, 'Keep off the grass.' Once the surgery was completed, the surgeon wrote a short note on the patient's
dressing, which said, 'Sorry, had to mow the lawn.'
Submitted by RN, no name
AND FINALLY!!!...
As a new, young MD doing his residency in OB , I was quite embarrassed when performing female pelvic exams. To cover my embarrassment, I had unconsciously formed a habit of whistling softly.
The middle-aged lady upon whom I was performing this exam suddenly burst out laughing and further embarrassing me. I looked up from my work and sheepishly said, 'I'm sorry. Was I tickling you?' She replied, 'No doctor, but the song you were whistling was, 'I wish I was an Oscar Meyer Wiener.'
Doctor wouldn't submit his name (Can't blame him!)
Monday, October 27, 2008
No more Baby Manjis in India, draft law on Surrogacy ready
New laws to regulate assisted reproductive technology in India will be introduced to Parliament later this year. The text of the Assisted Reproductive Technology (Regulation) Bill 2008 was published last month by the Indian Council of Medical Research (ICMR) for public comment. The bill aims to regulate surrogacy arrangements in the country where regulation is lacking, in addition to other technologies including pre-implantation genetic diagnosis (PGD) and research on embryos.
The bill will set up a National Advisory Board for Assisted Reproductive Technology to oversee the delivery of the services in the country. A regulatory body, the Registration Authority, will grant licences to fertility clinics to store gametes and offer fertility services. Embryo research must be performed on embryos donated for research and not stored beyond 14 days. Researchers must apply for a licence from the Registration Authority to perform research on embryos. The bill will also make it a criminal offence to perform sex-selection procedures except to prevent or treat a sex-linked disorder or disease.
Media reports last August about a baby girl, Manyi Yamada, showed inadequacies in India's regulation of surrogacy, which was legalised in 2002. Manyi was born to an Indian surrogate mother, but the Japanese couple who arranged the surrogacy split up prior to the birth of the child. The child's biological father sought parental rights over the child but Indian laws were not clear on the status of foreign parents involved in surrogacy arrangements within its borders and the matter had to be decided in the
courts. The new bill will clarify this area by making a surrogate child the legitimate child of a separated or divorced couple. Foreigners seeking surrogacy arrangements in the country will be required to register with their embassy and will have to state with whom the child should be looked after in the event of one of the parent's death. Following surrogacy, the child's birth certificate will show the names of both genetic parents. The bill also forbids women under 21 from entering into surrogacy arrangements and from having more than three live births in their lifetime. Once a surrogate child attains the age of 18, they may apply for information about their surrogate parent.
India's Health Ministry does not keep official statistics on the number of surrogate births in the country but it is believed to be low. Media reports suggest that surrogacy arrangements in India can attract surrogate fees of between $12,000 to $30,000, with the industry being worth around $445m. The bill does not ban offering surrogate mothers compensation for their services. Dr P M Bhargava, a member of the ICMR who helped draft the bill, told the Times of India that, 'considering all the news about surrogacy, including the recent case of the Japanese child, we realised that the new law addresses all the problem areas'.
The bill was timetabled to be debated by the Indian Parliament in the winter session. It met with stiff opposition from the Medical community and will be now reviewed by the Indian Law Ministry.
The bill will set up a National Advisory Board for Assisted Reproductive Technology to oversee the delivery of the services in the country. A regulatory body, the Registration Authority, will grant licences to fertility clinics to store gametes and offer fertility services. Embryo research must be performed on embryos donated for research and not stored beyond 14 days. Researchers must apply for a licence from the Registration Authority to perform research on embryos. The bill will also make it a criminal offence to perform sex-selection procedures except to prevent or treat a sex-linked disorder or disease.
Media reports last August about a baby girl, Manyi Yamada, showed inadequacies in India's regulation of surrogacy, which was legalised in 2002. Manyi was born to an Indian surrogate mother, but the Japanese couple who arranged the surrogacy split up prior to the birth of the child. The child's biological father sought parental rights over the child but Indian laws were not clear on the status of foreign parents involved in surrogacy arrangements within its borders and the matter had to be decided in the
courts. The new bill will clarify this area by making a surrogate child the legitimate child of a separated or divorced couple. Foreigners seeking surrogacy arrangements in the country will be required to register with their embassy and will have to state with whom the child should be looked after in the event of one of the parent's death. Following surrogacy, the child's birth certificate will show the names of both genetic parents. The bill also forbids women under 21 from entering into surrogacy arrangements and from having more than three live births in their lifetime. Once a surrogate child attains the age of 18, they may apply for information about their surrogate parent.
India's Health Ministry does not keep official statistics on the number of surrogate births in the country but it is believed to be low. Media reports suggest that surrogacy arrangements in India can attract surrogate fees of between $12,000 to $30,000, with the industry being worth around $445m. The bill does not ban offering surrogate mothers compensation for their services. Dr P M Bhargava, a member of the ICMR who helped draft the bill, told the Times of India that, 'considering all the news about surrogacy, including the recent case of the Japanese child, we realised that the new law addresses all the problem areas'.
The bill was timetabled to be debated by the Indian Parliament in the winter session. It met with stiff opposition from the Medical community and will be now reviewed by the Indian Law Ministry.
Sunday, October 26, 2008
P'njaab Airways : In-Flight Announcement
Gud marning, Ladies and Gen'lemen. P'rajee aur Behnjee. Sat Sri Akal.
On behalf of Captaan Balbir Singh 'Bobby', this is your Flight Supervisor Banta Singh "Bunty" welcoming to you on the P'njaab Airways flight no. 9211 (Nau Do Gyaraah) to Ludhiana.
We apalogize for the two-day delay in taking off, b'cause the sun was not shining brightly in the fog. And we are knowing the sun does not shine in the night.
Landing in Ludhiana is not dafinite, but with good luck we can be landing d'rectly in your v'llage.
P'njaab Airways has exc'llant record for safety. In fact our safety standards are so high that even the fully trained tarrists and hijackers are afraid to fly with us.
I am pleased to 'nounce that starting this year over 90% of our p'ssaingers have reached to their dest'nation.
For the rest 10%, the P'njaab Airways staff has lots of experience for consoling the next-of-kin. Our Hostess Bubbly Kaur will be haippy to brief you on our out-of-court settlement policies.
If engines are too noisy, on p'ssainger request, we can turn them off for comfart, but your flight will become late and you may become the late also.
For our religious p'ssaingers, we are the only airline who can help you to contact God at once. In case of sudden loss of cabin pressure, Holy Books will be quickly distributed.
We regret that today's in-flight movie will not be shown as we could not record it from the tallyvision due to power cut.
But we will be flying right naxt to Air India, where their movie can be seen from the right side cabin windows. These windows have been opened
For your viewing convenience. For p'ssaingers on left side, we have put binoculars under the seat.
If AirIndia flight is again cancelled, then for your in-flight ent'tainment. Our hostesses Bubbly Kaur & Cuckoo Kaur will do the Bhangra with flight stewards Pappu and Tappu. Oye, Balle Balle!!
Your in-flight Menu has a choice of Chicken Tikka Masala, Tandoori Fish, Dal makhani, unlimited P'ronthas and Lassi.
There is a half charge for Red Label Whiskey served from Black Label bottles. Patiala pegs will be served only on Patiala flights.
As per safety rules, smoking is not allowed on all P'njaab Airways flights over P'njaab. Any smoke you see in the cabin is only the early warning system on the engines.
Please do read the 'structions on the Safety Card in seat pocket in your front side. It is not a hand fan.
The P'ssainger behind you must read the card in your backside.
Life jackets are placed under your seats for emergency water landings on any of our 5 rivers. Do not use life jackets on the land.
Kindly keep your seat in upright position for take-off & landing. Also do not use force. Broken seats will not be replaced and you will be tied to the floor during take off and landing.
Please be seated first and then fasten your seatbelts. Do not call for steward or airhostess for a glass of water when plane is taking off.
We are about to take-off. We wish you a pleasant flight. For air sikness problems we have echo friendly jute bags in the sit pokets
Thank you once again for flying with P'njaab Airways
On behalf of Captaan Balbir Singh 'Bobby', this is your Flight Supervisor Banta Singh "Bunty" welcoming to you on the P'njaab Airways flight no. 9211 (Nau Do Gyaraah) to Ludhiana.
We apalogize for the two-day delay in taking off, b'cause the sun was not shining brightly in the fog. And we are knowing the sun does not shine in the night.
Landing in Ludhiana is not dafinite, but with good luck we can be landing d'rectly in your v'llage.
P'njaab Airways has exc'llant record for safety. In fact our safety standards are so high that even the fully trained tarrists and hijackers are afraid to fly with us.
I am pleased to 'nounce that starting this year over 90% of our p'ssaingers have reached to their dest'nation.
For the rest 10%, the P'njaab Airways staff has lots of experience for consoling the next-of-kin. Our Hostess Bubbly Kaur will be haippy to brief you on our out-of-court settlement policies.
If engines are too noisy, on p'ssainger request, we can turn them off for comfart, but your flight will become late and you may become the late also.
For our religious p'ssaingers, we are the only airline who can help you to contact God at once. In case of sudden loss of cabin pressure, Holy Books will be quickly distributed.
We regret that today's in-flight movie will not be shown as we could not record it from the tallyvision due to power cut.
But we will be flying right naxt to Air India, where their movie can be seen from the right side cabin windows. These windows have been opened
For your viewing convenience. For p'ssaingers on left side, we have put binoculars under the seat.
If AirIndia flight is again cancelled, then for your in-flight ent'tainment. Our hostesses Bubbly Kaur & Cuckoo Kaur will do the Bhangra with flight stewards Pappu and Tappu. Oye, Balle Balle!!
Your in-flight Menu has a choice of Chicken Tikka Masala, Tandoori Fish, Dal makhani, unlimited P'ronthas and Lassi.
There is a half charge for Red Label Whiskey served from Black Label bottles. Patiala pegs will be served only on Patiala flights.
As per safety rules, smoking is not allowed on all P'njaab Airways flights over P'njaab. Any smoke you see in the cabin is only the early warning system on the engines.
Please do read the 'structions on the Safety Card in seat pocket in your front side. It is not a hand fan.
The P'ssainger behind you must read the card in your backside.
Life jackets are placed under your seats for emergency water landings on any of our 5 rivers. Do not use life jackets on the land.
Kindly keep your seat in upright position for take-off & landing. Also do not use force. Broken seats will not be replaced and you will be tied to the floor during take off and landing.
Please be seated first and then fasten your seatbelts. Do not call for steward or airhostess for a glass of water when plane is taking off.
We are about to take-off. We wish you a pleasant flight. For air sikness problems we have echo friendly jute bags in the sit pokets
Thank you once again for flying with P'njaab Airways
Saturday, October 25, 2008
Friday, October 24, 2008
Catholic Mothers
Even if you didn't grow up Catholic, you'll appreciate this one....
Four Catholic ladies are having coffee together, discussing how important
their children are.
The first one tells her friends, 'My son is a priest. When he walks
into a room, everyone calls him 'Father.'
The second Catholic woman chirps, 'Well, my son is a Bishop.
Whenever he walks into a room, people say, 'Your Grace' The third Catholic woman says smugly, 'Well, not to put you
down, but my son is a Cardinal.
Whenever he walks into a room, people say 'Your Eminence'
The fourth Catholic woman sips her coffee in silence
The first three women give her this subtle 'Well...?
She replies, 'My son is a gorgeous, 6'4', hard bodied, well hung, male stripper.
Whenever he walks into a room, women say, 'Oh! ...'My God'!!!
Four Catholic ladies are having coffee together, discussing how important
their children are.
The first one tells her friends, 'My son is a priest. When he walks
into a room, everyone calls him 'Father.'
The second Catholic woman chirps, 'Well, my son is a Bishop.
Whenever he walks into a room, people say, 'Your Grace' The third Catholic woman says smugly, 'Well, not to put you
down, but my son is a Cardinal.
Whenever he walks into a room, people say 'Your Eminence'
The fourth Catholic woman sips her coffee in silence
The first three women give her this subtle 'Well...?
She replies, 'My son is a gorgeous, 6'4', hard bodied, well hung, male stripper.
Whenever he walks into a room, women say, 'Oh! ...'My God'!!!
Thursday, October 23, 2008
Understanding embryo implantation offers insight
Scientists at the University of Oxford, UK, believe they have identified the way in which embryos implant in the uterus, providing essential information which may be used in the future for infertility treatments and offering hope to thousands of infertile couples. Implantation of an embryo to the lining of the mother's uterus is an essential process that takes place at an early stage of development. The embryo initially attaches and forms a contact with the uterus lining, which triggers a cascade of signals in both the embryo and the uterus. This allows cells from the embryo to start moving across into the uterus, finding blood vessels in the mother and eventually forming the placenta. Problems in the implantation process can lead to loss of potential pregnancies, even in couples trying to conceive without infertility problems. Current estimates suggest that infertility affects one in seven couples in the UK, with around 32,000 couples seeking infertility treatment each year. It is thought that a significant number of these patients could be infertile as a result of implantation problems.
The team of scientists, led by Professor Helen Mardon from the Nuffield Department of Obstetrics and Gynaecology at Oxford, along with Professor Anne J Ridley at King's College, London, added embryos to a layer of cells from uterus lining in a culture dish to mimic events in the womb. They were then able to video embryos implanting themselves in the cell layer, allowing
the scientists to dissect the molecular processes involved. Their findings were published in the journal Proceedings of the National Academy of Sciences.Their investigation led them identify two proteins that are essential players in the implantation process. They are from the Rho GTPase family of proteins, and ensure that cells in a particular part of the uterus lining
move out of the way of the 'invading' embryonic cells. Professor Mardon said: 'We have shown that two proteins, called Rac1 and RhoA, control the invasion. The first stimulates cells in the womb lining to move and allow the embryo to invade and implant properly while the second inhibits this. We believe this controlled balance of the two proteins is critical for successful implantation of the embryo. If the balance of RhoGTPases is altered, the cells of the womb lining don't migrate and the
embryo doesn't implant'.
The findings bring new hope to people with infertility issues. The new information will help the understanding of how this process works, and therefore aid 'the development of drugs to help embryos implant properly',
said Prof Mardon.
The team of scientists, led by Professor Helen Mardon from the Nuffield Department of Obstetrics and Gynaecology at Oxford, along with Professor Anne J Ridley at King's College, London, added embryos to a layer of cells from uterus lining in a culture dish to mimic events in the womb. They were then able to video embryos implanting themselves in the cell layer, allowing
the scientists to dissect the molecular processes involved. Their findings were published in the journal Proceedings of the National Academy of Sciences.Their investigation led them identify two proteins that are essential players in the implantation process. They are from the Rho GTPase family of proteins, and ensure that cells in a particular part of the uterus lining
move out of the way of the 'invading' embryonic cells. Professor Mardon said: 'We have shown that two proteins, called Rac1 and RhoA, control the invasion. The first stimulates cells in the womb lining to move and allow the embryo to invade and implant properly while the second inhibits this. We believe this controlled balance of the two proteins is critical for successful implantation of the embryo. If the balance of RhoGTPases is altered, the cells of the womb lining don't migrate and the
embryo doesn't implant'.
The findings bring new hope to people with infertility issues. The new information will help the understanding of how this process works, and therefore aid 'the development of drugs to help embryos implant properly',
said Prof Mardon.
Wednesday, October 22, 2008
Egg-sharing and Cryopreservation: for who's benefit?
Nataly Atalla's uncritical advertorial 'freeze and share: an evolution of egg sharing' in BioNews 476 (week 15/9/2008 - 21/9/2008) did not address a number of important points.
I would have expected some comment on the success rate of the vitrification technique in their hands. She cites 100,000 procedures in 12 countries and 95 per cent survival and 96 per cent fertilisation rates being reported, but makes no mention of live delivery rates and in particular no reference to the results at her own unit, the London Bridge Fertility Gynaecology and Genetics Centre (the Bridge Centre). Results presented at the recent European Society of Human Reproduction and Embryology (ESHRE) meeting in Barcelona were very encouraging. Chang et al in Atlanta, Georgia, US, vitrified and warmed 155 mature donated oocytes, 135 survived and 117 fertilised with ICSI. They transferred 52 blastocysts into 20 recipients and detected 29 fetal hearts in 17 recipients (1).
However, great care needs to be taken when comparing results elsewhere with those in the UK. In the US, success rates per fresh cycle of egg donation treatment are commonly quoted as being over 60 per cent, whereas the Bridge Centre's most recent published results (HFEA 2007 clinical pregnancy data) was 27 per cent (9/34). This discrepancy is probably due to
the age of the donors - 23 year-old eggs can always be expected to do better than 33 year-old eggs. The vitrification technique may prove to be better than slow freezing but cryopreservation followed by IVF and embryo transfer cannot be expected to give better results than those achieved with fresh embryos. Further, slow freezing results vary from clinic to clinic and the same is likely to be the case with vitrification. Vitrification is more demanding in the laboratory than freezing because precisely controlled exposure to the vitrification solution before cooling and the subsequent rate of warming are critical for survival (2). In the 'freeze and share' scheme, vulnerable women as they approach their mid-30s are being encouraged to put their faith in a storage technique with as yet unproven efficacy in the hands of a clinic offering to exchange storage for eggs to donate to other women. These women may then delay childbearing, become infertile, not conceive with their own stored eggs and know that a woman or women conceived with the fresh eggs they donated some years previously.
How many eggs should the donor store to give herself a 'reasonable' chance of success should she find she needs to use them? Motta et al in Sao Paulo, Brazil and Michigan, US, using excess eggs vitrified and stored and subsequently, if the woman did not conceive following fresh embryo transfer, warmed and ICSI'd, achieved a clinical pregnancy rate of 38 per cent (3).
Although the eggs they used were provided by women with a fertility problem this result is much more like what we could expect in the UK. They estimated that 17 cryopreserved oocytes were required to establish a single clinical pregnancy. At the Bridge Centre suitable donors will undergo three treatment cycles in a year. If they are to store that number of eggs they will need, in order to give half to the recipient, to produce 34 mature eggs, say a total of 40 eggs from about 50 - 60 follicles. It can be seen that this will require a degree of overstimulation with the risks that that would incur.
What proportion of women storing their eggs will need them later? Atalla's commentary makes it clear that only women who are likely to respond to relatively low doses of fertility drugs will qualify to be donors. These women are less likely than those not suitable to donate to have difficulty conceiving in their late thirties and early forties. It appears therefore that the women who are least likely to need the eggs are storing their eggs - perhaps the idea is that they will donate these eggs to the women who were not suitable to donate and store their eggs? A win / win situation for the clinic?
References
(1) C.C. Chang et al, 'Clinical evaluation of blastocyst transfer in oocyte cryopreservation cycles' (P-369 Poster. Abstracts of the 24th Annual Meeting of the ESHRE. Barcelona, Spain, 7-9 July, 2008).
(2) M. Wood, 'Vitrified embryos and oocytes: the way forward' (O-092 Oral. Abstracts of the 24th Annual Meeting of the ESHRE. Barcelona, Spain, 7-9 July, 2008).
(3) E. Motta et al, 'Prospective randomised study of human oocyte cryopreservation by slow-rate freezing or vitrification' (P-374 Poster. Abstracts of the 24th Annual Meeting of the ESHRE. Barcelona, Spain, 7-9 July, 2008).
- John Parsons, Lead Consultant for King's Assisted Conception Unit
I would have expected some comment on the success rate of the vitrification technique in their hands. She cites 100,000 procedures in 12 countries and 95 per cent survival and 96 per cent fertilisation rates being reported, but makes no mention of live delivery rates and in particular no reference to the results at her own unit, the London Bridge Fertility Gynaecology and Genetics Centre (the Bridge Centre). Results presented at the recent European Society of Human Reproduction and Embryology (ESHRE) meeting in Barcelona were very encouraging. Chang et al in Atlanta, Georgia, US, vitrified and warmed 155 mature donated oocytes, 135 survived and 117 fertilised with ICSI. They transferred 52 blastocysts into 20 recipients and detected 29 fetal hearts in 17 recipients (1).
However, great care needs to be taken when comparing results elsewhere with those in the UK. In the US, success rates per fresh cycle of egg donation treatment are commonly quoted as being over 60 per cent, whereas the Bridge Centre's most recent published results (HFEA 2007 clinical pregnancy data) was 27 per cent (9/34). This discrepancy is probably due to
the age of the donors - 23 year-old eggs can always be expected to do better than 33 year-old eggs. The vitrification technique may prove to be better than slow freezing but cryopreservation followed by IVF and embryo transfer cannot be expected to give better results than those achieved with fresh embryos. Further, slow freezing results vary from clinic to clinic and the same is likely to be the case with vitrification. Vitrification is more demanding in the laboratory than freezing because precisely controlled exposure to the vitrification solution before cooling and the subsequent rate of warming are critical for survival (2). In the 'freeze and share' scheme, vulnerable women as they approach their mid-30s are being encouraged to put their faith in a storage technique with as yet unproven efficacy in the hands of a clinic offering to exchange storage for eggs to donate to other women. These women may then delay childbearing, become infertile, not conceive with their own stored eggs and know that a woman or women conceived with the fresh eggs they donated some years previously.
How many eggs should the donor store to give herself a 'reasonable' chance of success should she find she needs to use them? Motta et al in Sao Paulo, Brazil and Michigan, US, using excess eggs vitrified and stored and subsequently, if the woman did not conceive following fresh embryo transfer, warmed and ICSI'd, achieved a clinical pregnancy rate of 38 per cent (3).
Although the eggs they used were provided by women with a fertility problem this result is much more like what we could expect in the UK. They estimated that 17 cryopreserved oocytes were required to establish a single clinical pregnancy. At the Bridge Centre suitable donors will undergo three treatment cycles in a year. If they are to store that number of eggs they will need, in order to give half to the recipient, to produce 34 mature eggs, say a total of 40 eggs from about 50 - 60 follicles. It can be seen that this will require a degree of overstimulation with the risks that that would incur.
What proportion of women storing their eggs will need them later? Atalla's commentary makes it clear that only women who are likely to respond to relatively low doses of fertility drugs will qualify to be donors. These women are less likely than those not suitable to donate to have difficulty conceiving in their late thirties and early forties. It appears therefore that the women who are least likely to need the eggs are storing their eggs - perhaps the idea is that they will donate these eggs to the women who were not suitable to donate and store their eggs? A win / win situation for the clinic?
References
(1) C.C. Chang et al, 'Clinical evaluation of blastocyst transfer in oocyte cryopreservation cycles' (P-369 Poster. Abstracts of the 24th Annual Meeting of the ESHRE. Barcelona, Spain, 7-9 July, 2008).
(2) M. Wood, 'Vitrified embryos and oocytes: the way forward' (O-092 Oral. Abstracts of the 24th Annual Meeting of the ESHRE. Barcelona, Spain, 7-9 July, 2008).
(3) E. Motta et al, 'Prospective randomised study of human oocyte cryopreservation by slow-rate freezing or vitrification' (P-374 Poster. Abstracts of the 24th Annual Meeting of the ESHRE. Barcelona, Spain, 7-9 July, 2008).
- John Parsons, Lead Consultant for King's Assisted Conception Unit
Tuesday, October 21, 2008
Monday, October 20, 2008
Sunday, October 19, 2008
A Catholic Heart-attack
A man suffered a serious heart attack and had open heart bypass
surgery. He awakened from the surgery to find himself in the care of
nuns at a Catholic Hospital .
As he was recovering, a nun asked him questions regarding how he was
going to pay for his treatment. She asked if he had health insurance.
He replied, in a raspy voice, 'No health insurance.'
The nun asked if he had money in the bank.
He replied. 'No money in the bank.'
The nun asked, 'Do you have a relative who could help you?'
He said, 'I only have a spinster sister, who is a nun.'
The nun became agitated and announced loudly, 'Nuns are not spinsters!
Nuns are married to God.'
The patient replied, 'Send the bill to my brother-in -law.
surgery. He awakened from the surgery to find himself in the care of
nuns at a Catholic Hospital .
As he was recovering, a nun asked him questions regarding how he was
going to pay for his treatment. She asked if he had health insurance.
He replied, in a raspy voice, 'No health insurance.'
The nun asked if he had money in the bank.
He replied. 'No money in the bank.'
The nun asked, 'Do you have a relative who could help you?'
He said, 'I only have a spinster sister, who is a nun.'
The nun became agitated and announced loudly, 'Nuns are not spinsters!
Nuns are married to God.'
The patient replied, 'Send the bill to my brother-in -law.
Saturday, October 18, 2008
Friday, October 17, 2008
Thursday, October 16, 2008
Intracytoplasmic Sperm Injection ( ICSI )
Although cases presenting with mild sperm abnormalities can be successfully treated by "classical" IVF, today intracytoplasmic sperm injection ( ICSI ) offers a new dimension of therapy for all the moderate and more severe forms of male infertility.
Indications for ICSI include:
Men presenting with low sperm concentration, motility and / or morphology (irrespective of the degree of these abnormalities), antisperm antibodies, or with poor scores in the functional bioassays
Cases of partial or total fertilization failure in a previous IVF attempt ( with overt or more subtle sperm deficiencies or even with normal semen analysis )
Men presenting with absence of sperm in the ejaculate ( azoospermia ).
These cases were typically considered irreversible with donor sperm or adoption being considered as the only viable options. These challenging cases include two main types of problems:
-obstructive lesions of the male genital tract ( such as congenital bilateral absence of the vas deferens, inflammatory occlusions, previous vasectomy, and others )
-patients presenting with different degrees of testicular insufficiency ( hypospermatogenesis or poor sperm production of testicular origin ).
The former cases can be successfully treated by new techniques of sperm aspiration from the epididymis or the vas deferens followed by ICSI. In the latter cases, sperm can be obtained from the testes by performing an open testicular biopsy or by needle aspiration, also followed by ICSI.
In all these cases, the possibility of freezing "extra" sperm obtained at the time of the urological intervention ( prior to or at the time of IVF / ICSI ) should always be considered. Frozen - thawed sperm may maintain viability and therefore can be used in future ICSI cycles. Sperm freezing is a mandatory and efficient means of maintaining the reproductive potential of men who will have radical therapies in cases of curable cancer. Our sperm bank is ISO 9001:2000 certified and serves local, out - of - state, and international physicians and patients.
Because of the high incidence of male infertility and the outstanding success of the technique, currently we perform ICSI in 40% of all IVF cases. For this technique, success has to be assessed both in terms of fertilization and pregnancy outcome.
There are probably several thousand babies born worldwide through ICSI. Worldwide registries note that in 97% or more of the times that ICSI results in delivery of normal healthy babies. These numbers are probably very close to the results achieved in standard IVF therapy and probably not far from natural reproduction.
However, we are learning more and more about incidences of chromosomal / genetic problems in the infertile man. New techniques are being developed; statistics quote approximately 10% incidence of genetic or chromosomal abnormalities in men with either severely low sperm counts ( oligospermia ) or lack of sperm in the semen ( azoospermia ). For this reason, and in addition to performing a chromosomal evaluation of the fetus ( baby in the uterus ) in early pregnancy either by chorionic villus sampling or amniocentesis, the Jones Institute recommends a genetic consultation.
Intracytoplasmic sperm injection ( ICSI ) research has focused on the impact of ICSI on the meiotic spindle. The spindle is a "web like" intracellular structure that is crucial for normal chromosome alignment and separation during fertilization. We now use a highly specialized imaging system for ICSI procedures, which allows us to visualize and avoid damaging the meiotic spindle. Extensive research indicates that overall there is no increase in the rate of birth defects or other abnormalities after the ICSI procedure.
However, there is some concern that ICSI could increase the incidence of male infertility in offspring and that it could enhance the occurrence of rare sexual chromosomal abnormalities. In nature, the most viable sperm reaches and fertilizes the egg; however, in ICSI, sperm are manually selected thus bypassing this natural selection process. Clinical data are not yet available to conclusively rule out this possibility. We recommend that men with severe oligospermia or non - obstructive azoospermic undergo a baryotype ( blood chromosomal analysis ) and an examination of presence / absence of microdeletions of a Y - chromosome. Genetic counseling is offered as appropriate.
Wednesday, October 15, 2008
Tuesday, October 14, 2008
Monday, October 13, 2008
Conquering the 'ewww' factor of the public potty
ATLANTA, Georgia (CNN) – Most of us have them — the personal ritual to deal with the “ick” of a public bathroom: wiping the seat with toilet paper, using a paper seat cover or even rolling up several pieces of toilet paper to create a thicker barrier between the skin and … the unknown.
But the toilet seat is actually the cleanest part of the bathroom, one expert says.
Charles Gerba, a microbiologist at the University of Arizona who has studied restrooms and other germ-infested environments for more than 20 years, says that because of the care people take when they’re about to sit, other parts of the bathroom are much more prone to delivering bacterial infections.
“One of the cleanest things in the bathrooms we find are the toilet seats,” Gerba said. “I’d put my fanny on it any time — unless it’s wet; then you’d want to wipe it first.” Avoiding bathroom ‘hot spots’ »
The Internet has come through for people who just want a clean place to go. New tools like MizPee (nationwide) and Diaroogle (New York only) will point you to the nearest public restroom and display extensive comments about those facilities from users, even delivering the information to your mobile phone. (Warning: CNN makes no promises about the cleanliness of the language in these bathroom locators.)
MizPee launched a year ago for people in San Francisco, California, after co-founder Peter Olfe saw that the city’s public library bathroom was “so disgusting,” said Dhana Pawar, vice president and co-founder of Yojo Mobile, which created MizPee. “Unfortunately, [MizPee] was inspired by that trip.”
Fueled by demand, MizPee has expanded to more than 22 cities in America and six in Europe, and has had more than 300,000 unique visitors. Users rate toilets on a scale from one to five toilet paper rolls and nominate the best and worst toilets for the Flush of the Year award. The site also gives users information on deals at restaurants, shops and services nearby, in addition to toilet trivia called “looisms.”
Women tend to have higher standards for bathroom cleanliness than men, often rating any given unisex bathroom lower than men, Pawar said. In general, many more women than men use the site, but male bikers and older men, especially colitis patients, also come to MizPee.
Women are also particularly concerned about finding clean bathrooms with changing stations, Pawar said. “You’d be surprised how few there are.”
Pawar said she herself is “really paranoid” when it comes to the restroom.
“I’m one of those really anal people who have to have a clean bathroom,” she said.
For many people, public bathrooms generate feelings of anxiety, fear and disgust.
“Basically, everybody is fearful of public restrooms,” said Dr. Lisa Bernstein, assistant professor at Emory University School of Medicine, who admitted that her mother always told her that she should never make direct contact with a toilet seat.
Research indicates that fear of the commode itself may be misdirected.
Public bathrooms may contain several kinds of harmful bacteria, including E. coli, salmonella, coliform, rotavirus, cold virus and the potentially deadly form of staph known as MRSA, experts say. But people are more likely to pick up these nasty bugs through touching things in the bathroom with their hands, not their behinds.
“I don’t think anyone would voluntarily sit on a seat with urine, but, in reality, urine touching intact skin on the tush won’t do anything,” Bernstein said.
More concerning, however, is a child who steadies himself or herself on a toilet seat by holding onto it and then leaving without washing hands, she said. Those germs could lead to an infection once the child’s hands touch the nose, mouth or eyes.
And don’t forget that unwashed hands have handled everything from the door knob to the lock to the flusher. Again, if you touch one of these objects and then rub your eye, nose or mouth, you’re apt to transmit that bacteria.
But there is hope. Here are hygiene helpers:
Wash your hands
Yes, it’s basic. But, in general, washing your hands is the most effective action you can take to prevent bacterial infections from a public bathroom, experts say.
“You can remove all gastrointestinal and respiratory infection bacteria by washing hands,” said Judy Daly, clinical microbiologist at the University of Utah and spokesperson for the Clean Hands Campaign. “Seventeen seconds of a little bit of friction, water and soap will really mediate bacteria.”
The American Society for Microbiology, which sponsors the Clean Hands Campaign, found in a study last year that about 77 percent of men and women washed their hands in public restrooms, down 6 percent from 2005. The observational study also found that women washed their hands more than men.
“It’s such an easy intervention,” Daly said. “If you get it to be a habit for a 30-day period, it’s something you do automatically.”
Use automatic devices
Recent bathroom additions like automatic hands-free faucets and paper towel dispensers diminish contact between your hands and bathroom items that may bear bacteria, Bernstein said.
Don’t let your belongings touch the floor
Gerba’s research found that the highest concentration of germs in a public bathroom are on the floor, the outside of the sanitary napkin disposal and the sink and water taps.
When Gerba looked at women’s purses, he found that one-third of them had fecal bacteria on the bottom. Make sure you hang your shoulder bag on a hook. If none is available, some people swear by hanging the strap around their necks.
Use the first stall
The middle stall of a public restroom usually has the most bacteria because people use it the most. “I guess people like company,” Gerba said. The first stall will probably be cleaner.
Recognize the best and the worst
As a rule, the cleanest toilets are usually in hospitals, because they use disinfectants heavily, but the worst are in airports and airplanes, Gerba said. The small size of airplane bathrooms, including the sinks themselves, make it hard for people to wash their hands — in fact, Gerba’s study found a thin layer of E. coli in an airplane bathroom.
As for the airports themselves, “In the men’s room at Chicago O’Hare, I don’t think the toilet seat ever gets cold,” Gerba said.
Don’t hold back
It’s fine for a woman to hover over the toilet seat if she doesn’t want to sit down, but if she doesn’t empty her bladder completely, she’s at risk for a urinary infection, Bernstein said.
“You may be doing yourself more harm than good,” she said.
Along the same lines, you can develop urinary infections from “holding it in” too long just because you don’t want to use a particular facility. Better in a public stall than not at all.
Put it in perspective
Although the bathroom seems like a nasty place, the possible infections from the dreaded stall are no different from the ones you can get anywhere else in public.
“They’re the same bugs we transmit shaking hands,” Bernstein said. “People are more freaked out about restrooms, but the same thing applies anywhere in public.”
After all that research — he’s had the cops called on him while prowling around bathroom floors — Gerba has no problem with sitting down on public toilets. But Bernstein still uses one or two seat covers, “because of what my mother taught me,” she said.
By Elizabeth Landau
CNN
But the toilet seat is actually the cleanest part of the bathroom, one expert says.
Charles Gerba, a microbiologist at the University of Arizona who has studied restrooms and other germ-infested environments for more than 20 years, says that because of the care people take when they’re about to sit, other parts of the bathroom are much more prone to delivering bacterial infections.
“One of the cleanest things in the bathrooms we find are the toilet seats,” Gerba said. “I’d put my fanny on it any time — unless it’s wet; then you’d want to wipe it first.” Avoiding bathroom ‘hot spots’ »
The Internet has come through for people who just want a clean place to go. New tools like MizPee (nationwide) and Diaroogle (New York only) will point you to the nearest public restroom and display extensive comments about those facilities from users, even delivering the information to your mobile phone. (Warning: CNN makes no promises about the cleanliness of the language in these bathroom locators.)
MizPee launched a year ago for people in San Francisco, California, after co-founder Peter Olfe saw that the city’s public library bathroom was “so disgusting,” said Dhana Pawar, vice president and co-founder of Yojo Mobile, which created MizPee. “Unfortunately, [MizPee] was inspired by that trip.”
Fueled by demand, MizPee has expanded to more than 22 cities in America and six in Europe, and has had more than 300,000 unique visitors. Users rate toilets on a scale from one to five toilet paper rolls and nominate the best and worst toilets for the Flush of the Year award. The site also gives users information on deals at restaurants, shops and services nearby, in addition to toilet trivia called “looisms.”
Women tend to have higher standards for bathroom cleanliness than men, often rating any given unisex bathroom lower than men, Pawar said. In general, many more women than men use the site, but male bikers and older men, especially colitis patients, also come to MizPee.
Women are also particularly concerned about finding clean bathrooms with changing stations, Pawar said. “You’d be surprised how few there are.”
Pawar said she herself is “really paranoid” when it comes to the restroom.
“I’m one of those really anal people who have to have a clean bathroom,” she said.
For many people, public bathrooms generate feelings of anxiety, fear and disgust.
“Basically, everybody is fearful of public restrooms,” said Dr. Lisa Bernstein, assistant professor at Emory University School of Medicine, who admitted that her mother always told her that she should never make direct contact with a toilet seat.
Research indicates that fear of the commode itself may be misdirected.
Public bathrooms may contain several kinds of harmful bacteria, including E. coli, salmonella, coliform, rotavirus, cold virus and the potentially deadly form of staph known as MRSA, experts say. But people are more likely to pick up these nasty bugs through touching things in the bathroom with their hands, not their behinds.
“I don’t think anyone would voluntarily sit on a seat with urine, but, in reality, urine touching intact skin on the tush won’t do anything,” Bernstein said.
More concerning, however, is a child who steadies himself or herself on a toilet seat by holding onto it and then leaving without washing hands, she said. Those germs could lead to an infection once the child’s hands touch the nose, mouth or eyes.
And don’t forget that unwashed hands have handled everything from the door knob to the lock to the flusher. Again, if you touch one of these objects and then rub your eye, nose or mouth, you’re apt to transmit that bacteria.
But there is hope. Here are hygiene helpers:
Wash your hands
Yes, it’s basic. But, in general, washing your hands is the most effective action you can take to prevent bacterial infections from a public bathroom, experts say.
“You can remove all gastrointestinal and respiratory infection bacteria by washing hands,” said Judy Daly, clinical microbiologist at the University of Utah and spokesperson for the Clean Hands Campaign. “Seventeen seconds of a little bit of friction, water and soap will really mediate bacteria.”
The American Society for Microbiology, which sponsors the Clean Hands Campaign, found in a study last year that about 77 percent of men and women washed their hands in public restrooms, down 6 percent from 2005. The observational study also found that women washed their hands more than men.
“It’s such an easy intervention,” Daly said. “If you get it to be a habit for a 30-day period, it’s something you do automatically.”
Use automatic devices
Recent bathroom additions like automatic hands-free faucets and paper towel dispensers diminish contact between your hands and bathroom items that may bear bacteria, Bernstein said.
Don’t let your belongings touch the floor
Gerba’s research found that the highest concentration of germs in a public bathroom are on the floor, the outside of the sanitary napkin disposal and the sink and water taps.
When Gerba looked at women’s purses, he found that one-third of them had fecal bacteria on the bottom. Make sure you hang your shoulder bag on a hook. If none is available, some people swear by hanging the strap around their necks.
Use the first stall
The middle stall of a public restroom usually has the most bacteria because people use it the most. “I guess people like company,” Gerba said. The first stall will probably be cleaner.
Recognize the best and the worst
As a rule, the cleanest toilets are usually in hospitals, because they use disinfectants heavily, but the worst are in airports and airplanes, Gerba said. The small size of airplane bathrooms, including the sinks themselves, make it hard for people to wash their hands — in fact, Gerba’s study found a thin layer of E. coli in an airplane bathroom.
As for the airports themselves, “In the men’s room at Chicago O’Hare, I don’t think the toilet seat ever gets cold,” Gerba said.
Don’t hold back
It’s fine for a woman to hover over the toilet seat if she doesn’t want to sit down, but if she doesn’t empty her bladder completely, she’s at risk for a urinary infection, Bernstein said.
“You may be doing yourself more harm than good,” she said.
Along the same lines, you can develop urinary infections from “holding it in” too long just because you don’t want to use a particular facility. Better in a public stall than not at all.
Put it in perspective
Although the bathroom seems like a nasty place, the possible infections from the dreaded stall are no different from the ones you can get anywhere else in public.
“They’re the same bugs we transmit shaking hands,” Bernstein said. “People are more freaked out about restrooms, but the same thing applies anywhere in public.”
After all that research — he’s had the cops called on him while prowling around bathroom floors — Gerba has no problem with sitting down on public toilets. But Bernstein still uses one or two seat covers, “because of what my mother taught me,” she said.
By Elizabeth Landau
CNN
Sunday, October 12, 2008
Saturday, October 11, 2008
The Peacock Flowers of Lavasa
But beauty seen is never lost,
God’s colors all are fast;
The glory of this sunset heaven
Into my soul has passed…..
-John Greenleaf Whittier, Sunset on the Bearcamp, 1876
It had been quite a while since I visited Lavasa. I was looking forward to smell the red earth again. This red earth has a fragrance different from any other part of India. I was missing my home in the mountains. As soon as I crossed the Lavasa Dwaar, I noticed the colors. There were flowers starting to bloom in the Mose valley. We were greeted with red gladioli in the newly laid out picturesque flower-beds!
Come experience the vibrant waves of color that have started covering the hillsides at Lavasa. This wonderful display of horticultural beauty surprised me and promises to welcome us into a sea of floral color and aromatic delights. The gardeners have been busy in the monsoons and their results are just showing. I must have gone up and down the slopes from Ekaant to Portofino more than a 50 times but this time was surprised with the vibrant peacock flowers of Lavasa - I stopped and walked in the sloping hill-side gardens for hours. It was a stunning day, beautiful sunshine, so the flowers were open and could be enjoyed. I had noticed a few flower-beds coming up on the hill slopes especially at vantage viewing areas after the Lavasa-Dwaar but these Peacock Flowers of Lavasa are something different. They have changed the blue and green Lavasa landscape to red and yellow sprinkled all over the green countryscape. My wife was the flower-expert this time and instantly diagnosed the flower-fields to be Caesalpinia Pulcherrima (I was impressed with a gynecologist identifying the flower type spot-on!).
In the genus Caesalpinia the most popularly planted species is Caesalpinia pulcherrima. Common names for this species include Poinciana, Peacock Flower, Red Bird of Paradise, Mexican Bird of Paradise, Dwarf Poinciana, Pride of Barbados, and flamboyan-de-jardin. It is a shrub growing to 3 m tall, native to tropical America. The leaves are bipinnate, 20-40 cm long, bearing 3-10 pairs of pinnae, each with 6-10 pairs of leaflets 15-25 mm long and 10-15 mm broad. The flowers are borne in racemes up to 20 cm long, each flower with five yellow, orange or red petals. The fruit is a pod 6-12 cm long. It is a striking ornamental plant, widely grown in tropical gardens. It is also the national flower of the Caribbean island of Barbados, and is depicted on the Queen's personal Barbadian flag. In India it is found in the tropical rain forests. With a beautiful inflorescence in yellow, red and orange, it is called "Ratnagundhi" colloquially.
Medicine men in the Amazon Rainforest have long known some of the medicinal uses for Caesalpinia pulcherrima, which is known as ayoowiri. The juice from the leaves is said to cure fever, the juice from the flower cures sores, and the seeds cure bad cough, breathing difficulty, and chest pain. Four grams from the root is also said to induce abortion in the first trimester of pregnancy.
Word lover that I am, I searched for the translation of Caesalpinia Pulcherrima, figuring it meant something like "the most beautiful king of plants" (since I know from Akeela and the Bee that pulcher is Latin for beauty, and I figured Caes... meant "king" like Caesar). What I found out is that Caesalpinia was named after Andrea Cesalpino (1519--1603), an Italian botanist (citation). And Pulcherrima, as I guessed, means "most beautiful."
And the playground of Poseidon still looks best at Dusk(see picture). Dusk refers to the period of time following sunset. Although commonly confused with twilight, dusk is the time frame that occurs either before or after a twilight - when the sky is still generally bright and blue, but there is no sun to accompany it.
Twilight, again. Another ending. No matter how perfect the day is, it always has to end.
Stephenie Meyer, Twilight, 2005
Friday, October 10, 2008
Thursday, October 9, 2008
Applications of PCR
The Polymerase Chain Reaction (PCR) has found widespread application in many areas of genetic analysis. This is a list of some of these applications:
1 Medical applications
2 Infectious disease applications
3 Forensic applications
4 Research applications
Medical applications
PCR has been applied to a large number of medical procedures:
The first application of PCR was for genetic testing, where a sample of DNA is analyzed for the presence of genetic disease mutations. Prospective parents can be tested for being genetic carriers, or their children might be tested for actually being affected by a disease. DNA samples for Prenatal testing can be obtained by amniocentesis, chorionic villus sampling, or even by the analysis of rare fetal cells circulating in the mother's bloodstream. PCR analysis is also essential to Preimplantation genetic diagnosis, where individual cells of a developing embryo are tested for mutations.
PCR can also be used as part of a sensitive test for tissue typing, vital to organ transplantation. As of 2008, there is even a proposal to replace the traditional antibody-based tests for blood type with PCR-based tests.
Many forms of cancer involve alterations to oncogenes. By using PCR-based tests to study these mutations, therapy regimens can sometimes be individually customized to a patient.
Infectious disease applications
Characterization and detection of infectious disease organisms have been revolutionized by PCR:
The Human Immunodeficiency Virus (or HIV), responsible for AIDS, is a difficult target to find and eradicate. The earliest tests for infection relied on the presence of antibodies to the virus circulating in the bloodstream. However, antibodies don't appear until many weeks after infection, maternal antibodies mask the infection of a newborn, and therapeutic agents to fight the infection don't affect the antibodies. PCR tests have been developed that can detect as little as one viral genome among the DNA of over 50,000 host cells . Infections can be detected earlier, donated blood can be screened directly for the virus, newborns can be immediately tested for infection, and the effects of antiviral treatments can be quantified.
Some disease organisms, such as that for Tuberculosis, are difficult to sample from patients and slow to be grown in the laboratory. PCR-based tests have allowed detection of small numbers of disease organisms (both live or dead), in convenient samples. Detailed genetic analysis can also be used to detect antibiotic resistance, allowing immediate and effective therapy. The effects of therapy can also be immediately evaluated.
The spread of a disease organism through populations of domestic or wild animals can be monitored by PCR testing. In many cases, the appearance of new virulent sub-types can be detected and monitored. The sub-types of an organism that were responsible for earlier epidemics can also be determined by PCR analysis.
Forensic applications
The development of PCR-based genetic (or DNA) fingerprinting protocols has seen widespread application in forensics:
In its most discriminating form, Genetic fingerprinting can uniquely discriminate any one person from the entire population of the world. Minute samples of DNA can be isolated from a crime scene, and compared to that from suspects, or from a DNA database of earlier evidence or convicts. Simpler versions of these tests are often used to rapidly rule out suspects during a criminal investigation. Evidence from decades-old crimes can be tested, confirming or exonerating the people originally convicted.
Less discriminating forms of DNA fingerprinting can help in Parental testing, where an individual is matched with their close relatives. DNA from unidentified human remains can be tested, and compared with that from possible parents, siblings, or children. Similar testing can be used to confirm the biological parents of an adopted (or kidnapped) child. The actual biological father of a newborn can also be confirmed (or ruled out).
[edit]Research applications
PCR has been applied to many areas of research in molecular genetics:
PCR allows rapid production of short pieces of DNA, even when nothing more than the sequence of the two primers is known. This ability of PCR augments many methods, such as generating hybridization probes for Southern or northern blot hybridization. PCR supplies these techniques with large amounts of pure DNA, sometimes as a single strand, enabling analysis even from very small amounts of starting material.
The task of DNA sequencing can also be assisted by PCR. Known segments of DNA can easily be produced from a patient with a genetic disease mutation. Modifications to the amplification technique can extract segments from a completely unknown genome, or can generate just a single strand of an area of interest.
PCR has numerous applications to the more traditional process of DNA cloning. It can extract segments for insertion into a vector from a larger genome, which may be only available in small quantities. Using a single set of 'vector primers', it can also analyze or extract fragments that have already been inserted into vectors. Some alterations to the PCR protocol can generate mutations (general or site-directed) of an inserted fragment.
Sequence-tagged sites is a process where PCR is used as an indicator that a particular segment of a genome is present in a particular clone. The Human Genome Project found this application vital to mapping the cosmid clones they were sequencing, and to coordinating the results from different laboratories.
An exciting application of PCR is the phylogenic analysis of DNA from ancient sources, such as that found in the recovered bones of Neanderthals, or from frozen tissues of Mammoths. In some cases the highly degraded DNA from these sources might be reassembled during the early stages of amplification.
A common application of PCR is the study of patterns of gene expression. Tissues (or even individual cells) can be analyzed at different stages to see which genes have become active, or which have been switched off. This application can also use Q-PCR to quantitate the actual levels of expression.
The ability of PCR to simultaneously amplify several loci from individual sperm has greatly enhanced the more traditional task of genetic mapping by studying chromosomal crossovers after meiosis. Rare crossover events between very close loci have been directly observed by analyzing thousands of individual sperms. Similarly, unusual deletions, insertions, translocations, or inversions can be analyzed, all without having to wait (or pay for) the long and laborious processes of fertilization, embryogenesis, etc.
1 Medical applications
2 Infectious disease applications
3 Forensic applications
4 Research applications
Medical applications
PCR has been applied to a large number of medical procedures:
The first application of PCR was for genetic testing, where a sample of DNA is analyzed for the presence of genetic disease mutations. Prospective parents can be tested for being genetic carriers, or their children might be tested for actually being affected by a disease. DNA samples for Prenatal testing can be obtained by amniocentesis, chorionic villus sampling, or even by the analysis of rare fetal cells circulating in the mother's bloodstream. PCR analysis is also essential to Preimplantation genetic diagnosis, where individual cells of a developing embryo are tested for mutations.
PCR can also be used as part of a sensitive test for tissue typing, vital to organ transplantation. As of 2008, there is even a proposal to replace the traditional antibody-based tests for blood type with PCR-based tests.
Many forms of cancer involve alterations to oncogenes. By using PCR-based tests to study these mutations, therapy regimens can sometimes be individually customized to a patient.
Infectious disease applications
Characterization and detection of infectious disease organisms have been revolutionized by PCR:
The Human Immunodeficiency Virus (or HIV), responsible for AIDS, is a difficult target to find and eradicate. The earliest tests for infection relied on the presence of antibodies to the virus circulating in the bloodstream. However, antibodies don't appear until many weeks after infection, maternal antibodies mask the infection of a newborn, and therapeutic agents to fight the infection don't affect the antibodies. PCR tests have been developed that can detect as little as one viral genome among the DNA of over 50,000 host cells . Infections can be detected earlier, donated blood can be screened directly for the virus, newborns can be immediately tested for infection, and the effects of antiviral treatments can be quantified.
Some disease organisms, such as that for Tuberculosis, are difficult to sample from patients and slow to be grown in the laboratory. PCR-based tests have allowed detection of small numbers of disease organisms (both live or dead), in convenient samples. Detailed genetic analysis can also be used to detect antibiotic resistance, allowing immediate and effective therapy. The effects of therapy can also be immediately evaluated.
The spread of a disease organism through populations of domestic or wild animals can be monitored by PCR testing. In many cases, the appearance of new virulent sub-types can be detected and monitored. The sub-types of an organism that were responsible for earlier epidemics can also be determined by PCR analysis.
Forensic applications
The development of PCR-based genetic (or DNA) fingerprinting protocols has seen widespread application in forensics:
In its most discriminating form, Genetic fingerprinting can uniquely discriminate any one person from the entire population of the world. Minute samples of DNA can be isolated from a crime scene, and compared to that from suspects, or from a DNA database of earlier evidence or convicts. Simpler versions of these tests are often used to rapidly rule out suspects during a criminal investigation. Evidence from decades-old crimes can be tested, confirming or exonerating the people originally convicted.
Less discriminating forms of DNA fingerprinting can help in Parental testing, where an individual is matched with their close relatives. DNA from unidentified human remains can be tested, and compared with that from possible parents, siblings, or children. Similar testing can be used to confirm the biological parents of an adopted (or kidnapped) child. The actual biological father of a newborn can also be confirmed (or ruled out).
[edit]Research applications
PCR has been applied to many areas of research in molecular genetics:
PCR allows rapid production of short pieces of DNA, even when nothing more than the sequence of the two primers is known. This ability of PCR augments many methods, such as generating hybridization probes for Southern or northern blot hybridization. PCR supplies these techniques with large amounts of pure DNA, sometimes as a single strand, enabling analysis even from very small amounts of starting material.
The task of DNA sequencing can also be assisted by PCR. Known segments of DNA can easily be produced from a patient with a genetic disease mutation. Modifications to the amplification technique can extract segments from a completely unknown genome, or can generate just a single strand of an area of interest.
PCR has numerous applications to the more traditional process of DNA cloning. It can extract segments for insertion into a vector from a larger genome, which may be only available in small quantities. Using a single set of 'vector primers', it can also analyze or extract fragments that have already been inserted into vectors. Some alterations to the PCR protocol can generate mutations (general or site-directed) of an inserted fragment.
Sequence-tagged sites is a process where PCR is used as an indicator that a particular segment of a genome is present in a particular clone. The Human Genome Project found this application vital to mapping the cosmid clones they were sequencing, and to coordinating the results from different laboratories.
An exciting application of PCR is the phylogenic analysis of DNA from ancient sources, such as that found in the recovered bones of Neanderthals, or from frozen tissues of Mammoths. In some cases the highly degraded DNA from these sources might be reassembled during the early stages of amplification.
A common application of PCR is the study of patterns of gene expression. Tissues (or even individual cells) can be analyzed at different stages to see which genes have become active, or which have been switched off. This application can also use Q-PCR to quantitate the actual levels of expression.
The ability of PCR to simultaneously amplify several loci from individual sperm has greatly enhanced the more traditional task of genetic mapping by studying chromosomal crossovers after meiosis. Rare crossover events between very close loci have been directly observed by analyzing thousands of individual sperms. Similarly, unusual deletions, insertions, translocations, or inversions can be analyzed, all without having to wait (or pay for) the long and laborious processes of fertilization, embryogenesis, etc.
Wednesday, October 8, 2008
Tuesday, October 7, 2008
Non-invasive Prenatal Diagnosis using cell-free Fetal DNA
The holy grail of prenatal diagnosis has been the identification of chromosome and single gene abnormalities through maternal blood sampling. This would allow safe accurate prenatal diagnosis, requiring much lower operator skills, and automation is potentially possible, making it cost-effective. In contrast, standard prenatal screening involves ultrasound and biochemical risk assessment followed by invasive prenatal diagnosis by chorionic villus sampling (CVS), amniocentesis or fetal blood sampling - all requiring clinical expertise to perform and a variable risk of fetal loss.
The most common call is consistently from parents wrestling with the decision about whether to have an invasive test such as chorionic villus sampling (CVS) or amniocentesis. Because both procedures carry a one per cent risk of miscarriage, parents agonise over whether to put their pregnancy at risk in order to have conclusive information on a genetic condition. If cffDNA testing were to provide risk-free but reliable diagnoses of aneuploidies and other genetic conditions it would prove extremely popular with many parents.For most parents the earlier reassurance that cffDNA testing would bring will be welcome. However, we must avoid making assumptions that an earlier diagnosis will necessarily be easier for parents to cope with. Making painful decisions about the future of what is most often a wanted pregnancy is difficult at any gestation. Furthermore, there is no evidence that earlier terminations for fetal abnormality have substantially less emotional impact on women and couples than those carried out later in the pregnancy.
Another concern from the parental perspective is the form cffDNA testing takes, being a simple blood test. Women are very accustomed to having blood taken in pregnancy and while holding out an arm for a needle to be inserted is not always pleasant, it is something with which every pregnant woman is familiar. The 'routine' nature of the procedure could mean that some women embark on it without considering the possible implications and so are particularly distressed if test results bring unexpected news about the pregnancy. This has implications for how pre-test counselling and consent issues are handled.
In fact there is a precedent for a non-invasive diagnostic tool in routine use in antenatal care, namely ultrasound scanning. Every time an ultrasound probe is placed on the abdomen of a pregnant woman there is the possibility that an abnormality will be detected. Although information provision to women about the purpose of antenatal ultrasound is improving, we cannot underestimate the profound impact on parents when the scan shows that there is something wrong. However well-informed a woman may be, such news will always come as a shock and generate considerable anxiety and distress. This will also be the case for a diagnosis made from cffDNA testing, even if it comes earlier in pregnancy.
For decades, attempts to identify intact fetal cells in the maternal circulation have been unsuccessful - too few cells were present, and the few that were identified could remain in the circulation for years. Cell-free DNA is also present in the circulation and probably arises from apoptosis (controlled cell death) of cells. Fetal DNA arises from dying trophoblast cells and comprises 3-6 per cent of the total cell free DNA in the maternal circulation. FfDNA was first demonstrated in the maternal circulation in 1997, it consists of short fragments of DNA, not whole chromosomes. It can be first identified from the fourth week of gestation and increases throughout pregnancy. It is rapidly cleared from the maternal circulation after delivery and is undetectable by two hours. DNA is normally transcribed in to RNA and cell free RNA (ffRNA) also circulates in the maternal circulation. It is more stable than other forms of RNA. Only genes that are being transcribed will produce RNA and therefore identification of free fetal against free maternal RNA may be possible through differential expression patterns (ie. different patterns of maternal and fetal gene activity).
Identification of the ffDNA from the free maternal DNA is a major challenge. Fifty per cent of the genes in fetal DNA will be the same as in the maternal DNA, as they originate from the mother. Two clinical uses of ffDNA technologies are currently used frequently; rhesus typing and fetal sexing. Rhesus blood grouping of the fetus in rhesus negative mothers is used to try and prevent isoimmunisation of the fetus by using anti D antibodies in mothers carrying rhesus positive babies. Fetal sexing is offered to women who are either carriers of an X-linked disorder and who only need to have a CVS if they are carrying an at risk male, or women at a one in four risk of having an affected baby with congenital adrenal hyperplasia. In these pregnancies early maternal treatment with dexamethasone hopefully prevents the development of the distressing problem of clitoromegaly in affected girls.
However, the above two uses for ffDNA are only the very beginning for what is potentially possible with this technology. Screening for Down syndrome and other major trisomies (conditions caused by having three, rather than two copies of a particular chromosome) would transform prenatal diagnosis and screening. Diagnosis could be earlier and available to a much wider number of women. Single gene disorders can also be potentially identified using ffDNA. At present this is being studied in cases where the father is a carrier of an autosomal dominant disease - identification of the mutation has to be from ffDNA as the mother does not carry the mutation. If the father carries a different mutation in an autosomal recessive disease then this might also be possible to identify. Another potential use for ffDNA is where ultrasound abnormalities are identified and it may be possible to confirm a diagnosis using genetic tests and ffDNA. Examples of this include achondroplasia and thanatophoric dysplasia. In view of the limited volume of ffDNA available, it is only possible to look at specific well recognised mutations rather than screening a whole gene. FfRNA from genes that are only active in the placenta will allow wider applications of the technology, as there will be different patterns of gene activity from maternal ffRNA, and hence differentiating between the two should be easier.
Greater availability of risk free tests for prenatal diagnosis may sound ideal, but first it is necessary to confirm the reliability and accuracy of the test. Fetal sexing had an approximately four per cent error rate until recently. Fetal sexing can be confirmed using ultrasound at 16 weeks so the error can be rectified, but for tests with no ultrasound markers this will not be possible. In addition, not all women want prenatal diagnosis but all women have blood samples taken during pregnancy, so they may not realise what is being tested for and receive results that they are ill-prepared to receive. Biochemical screening has had some similar problems but as it is a screening test the woman then has a choice whether to proceed to a diagnostic test. Lastly there is the possibility of abusing the technology particularly for fetal sexing; this has happened in other modalities of prenatal diagnosis in both ultrasound and karyotyping. There is a possibility of ffDNA testing being available over the internet and therefore more difficult to control.
FfDNA technology thus has the potential to change the face of prenatal diagnosis, allowing safer and earlier diagnosis for a wide number of genetic diseases, and we look forward to these advances with anticipation and a degree of impatience.
The most common call is consistently from parents wrestling with the decision about whether to have an invasive test such as chorionic villus sampling (CVS) or amniocentesis. Because both procedures carry a one per cent risk of miscarriage, parents agonise over whether to put their pregnancy at risk in order to have conclusive information on a genetic condition. If cffDNA testing were to provide risk-free but reliable diagnoses of aneuploidies and other genetic conditions it would prove extremely popular with many parents.For most parents the earlier reassurance that cffDNA testing would bring will be welcome. However, we must avoid making assumptions that an earlier diagnosis will necessarily be easier for parents to cope with. Making painful decisions about the future of what is most often a wanted pregnancy is difficult at any gestation. Furthermore, there is no evidence that earlier terminations for fetal abnormality have substantially less emotional impact on women and couples than those carried out later in the pregnancy.
Another concern from the parental perspective is the form cffDNA testing takes, being a simple blood test. Women are very accustomed to having blood taken in pregnancy and while holding out an arm for a needle to be inserted is not always pleasant, it is something with which every pregnant woman is familiar. The 'routine' nature of the procedure could mean that some women embark on it without considering the possible implications and so are particularly distressed if test results bring unexpected news about the pregnancy. This has implications for how pre-test counselling and consent issues are handled.
In fact there is a precedent for a non-invasive diagnostic tool in routine use in antenatal care, namely ultrasound scanning. Every time an ultrasound probe is placed on the abdomen of a pregnant woman there is the possibility that an abnormality will be detected. Although information provision to women about the purpose of antenatal ultrasound is improving, we cannot underestimate the profound impact on parents when the scan shows that there is something wrong. However well-informed a woman may be, such news will always come as a shock and generate considerable anxiety and distress. This will also be the case for a diagnosis made from cffDNA testing, even if it comes earlier in pregnancy.
For decades, attempts to identify intact fetal cells in the maternal circulation have been unsuccessful - too few cells were present, and the few that were identified could remain in the circulation for years. Cell-free DNA is also present in the circulation and probably arises from apoptosis (controlled cell death) of cells. Fetal DNA arises from dying trophoblast cells and comprises 3-6 per cent of the total cell free DNA in the maternal circulation. FfDNA was first demonstrated in the maternal circulation in 1997, it consists of short fragments of DNA, not whole chromosomes. It can be first identified from the fourth week of gestation and increases throughout pregnancy. It is rapidly cleared from the maternal circulation after delivery and is undetectable by two hours. DNA is normally transcribed in to RNA and cell free RNA (ffRNA) also circulates in the maternal circulation. It is more stable than other forms of RNA. Only genes that are being transcribed will produce RNA and therefore identification of free fetal against free maternal RNA may be possible through differential expression patterns (ie. different patterns of maternal and fetal gene activity).
Identification of the ffDNA from the free maternal DNA is a major challenge. Fifty per cent of the genes in fetal DNA will be the same as in the maternal DNA, as they originate from the mother. Two clinical uses of ffDNA technologies are currently used frequently; rhesus typing and fetal sexing. Rhesus blood grouping of the fetus in rhesus negative mothers is used to try and prevent isoimmunisation of the fetus by using anti D antibodies in mothers carrying rhesus positive babies. Fetal sexing is offered to women who are either carriers of an X-linked disorder and who only need to have a CVS if they are carrying an at risk male, or women at a one in four risk of having an affected baby with congenital adrenal hyperplasia. In these pregnancies early maternal treatment with dexamethasone hopefully prevents the development of the distressing problem of clitoromegaly in affected girls.
However, the above two uses for ffDNA are only the very beginning for what is potentially possible with this technology. Screening for Down syndrome and other major trisomies (conditions caused by having three, rather than two copies of a particular chromosome) would transform prenatal diagnosis and screening. Diagnosis could be earlier and available to a much wider number of women. Single gene disorders can also be potentially identified using ffDNA. At present this is being studied in cases where the father is a carrier of an autosomal dominant disease - identification of the mutation has to be from ffDNA as the mother does not carry the mutation. If the father carries a different mutation in an autosomal recessive disease then this might also be possible to identify. Another potential use for ffDNA is where ultrasound abnormalities are identified and it may be possible to confirm a diagnosis using genetic tests and ffDNA. Examples of this include achondroplasia and thanatophoric dysplasia. In view of the limited volume of ffDNA available, it is only possible to look at specific well recognised mutations rather than screening a whole gene. FfRNA from genes that are only active in the placenta will allow wider applications of the technology, as there will be different patterns of gene activity from maternal ffRNA, and hence differentiating between the two should be easier.
Greater availability of risk free tests for prenatal diagnosis may sound ideal, but first it is necessary to confirm the reliability and accuracy of the test. Fetal sexing had an approximately four per cent error rate until recently. Fetal sexing can be confirmed using ultrasound at 16 weeks so the error can be rectified, but for tests with no ultrasound markers this will not be possible. In addition, not all women want prenatal diagnosis but all women have blood samples taken during pregnancy, so they may not realise what is being tested for and receive results that they are ill-prepared to receive. Biochemical screening has had some similar problems but as it is a screening test the woman then has a choice whether to proceed to a diagnostic test. Lastly there is the possibility of abusing the technology particularly for fetal sexing; this has happened in other modalities of prenatal diagnosis in both ultrasound and karyotyping. There is a possibility of ffDNA testing being available over the internet and therefore more difficult to control.
FfDNA technology thus has the potential to change the face of prenatal diagnosis, allowing safer and earlier diagnosis for a wide number of genetic diseases, and we look forward to these advances with anticipation and a degree of impatience.
Monday, October 6, 2008
Subscribe to:
Posts (Atom)