Table of contents :
vital procedures and finally reintroduction into the same (or another)
living organism.
is one of the most important performance parameters of blood pumps. Humans
can clear total doses of up to 14 g of free plasma hemoglobin per day if
their renal function is normal. Free plasma hemoglobin of up to 130 mg/dL
may be bound to form hemoglobin-haptoglobin complexes in vivo. Therefore,
if the plasma hemoglobin level exceeds this value, hemoglobinuria occurs
and leads to organ failure. Currently, comparive in vitro evaluations of
the reported hemolysis effects are difficult due to the lack of uniformity
of the test methods used. In the literature, 3 types of formulas are accepted
as indices of hemolysis. In order to avoid confusion, they are classified
as :
and/or heart surgery
(cava veins => aorta bypass).
It is a pulmonary technology capable of facilitated gas exchange in the
blood, thereby bypassing the alveolar-capillary interface. It consists
of the application of intermediate-term cardiopulmonary bypass for the
treatment of potentially reversible heart and/or lung failure in the neonate,
child, and adult. Applications in the neonate include congenital
diaphragmatic hernia (CDH),
pulmonary
arterial hypertension,
meconium
aspiration syndrome (MAS),
and pre- and post-operative congenital heart
surgery
support. In the older child, myocarditis,
infections,
and respiratory
failure
(RSV
and ARDS)
are the most frequent indications, in addition to peri-operative cardiac
surgical support. ECMO can provide this delivery without causing the iatrogenic
damage associated with high mechanical ventilation pressures, high fraction
of inspired oxygen, or high doses of inotropic medications. Though practitioners
use a multitude of other, more "conventional," therapies for neonatal respiratory
failure, only ECMO has been proven in a randomized, controlled, clinical
trial to improve both mortality and morbidity among neonates. The use of
inhaled nitric oxide (iNO) reduces the necessity for ECMO in newborns and
infants with acute hypoxemic respiratory failure.
|
|
|
|
|
| cellulose diacetate (hollow fiber) | Plasmaflo-AP05H (Asahi Medical, Tokyo, Japan) |
|
|
| Plasmaflo-AP05 (Asahi Medical) |
|
|
|
| polypropylene (hollow fiber) | Fenwal CPS-10 (Baxter, Deerfield, IL, USA) |
|
|
| Hemaplex-BT900 (Dideco, Mirrandola, MO, USA) |
|
|
|
| Curesis M82 (Organon Teknika, Durham, NC, USA) |
|
|
|
| polypropylene (flat plate) | Centry TPE (Cobe, Lakewood, CO, USA) |
|
|
| polysulfone (hollow fiber) | Sulflux-FS (Kaneka, New York, NY, USA) |
|
|
| polymethylmethacrylate (hollow fiber) | Plasmax-PS05 (Toray, Tokyo, Japan) |
|
|
or albumin or colloid solution (plasma
exchange (PE))
if they are not replaced with IVIg
with or without polyneuropathy
recipient
=> hyperviscosity
syndrome
and acute renal
failure (ARF))
presensitization-associated
recurrent focal
segmental glomerulosclerosis (FSGS)rejection
: PE removes mercaptans, GABA, phenolic acid, aromatic amino acids, liver
regeneration factors, cerebral activity inhibitors, sodium, potassium,
and ATP. Survival ranges from 18.0ref-30.0ref-33.3ref-37.5ref-66.7%ref
with polyneuropathy
are observed
: ethylene vinyl alcohol and acrylic copolymers may cause mild adverse
reaction in some patients taking ACEI
or Waldenstrom's
disease.
To prevent plugging reverse rinse of the secondary PF is carried. DFPP
is most commonly performed in Japan, but very rarely initiated in the USA.|
|
|
|
|
|
| ethylene vinyl alcohol | Evalfux 2A (Kuraray, Osaka, Japan) |
|
|
IgG, IgA |
| Evalfux 3A (Kuraray) |
|
|
cytokines | |
| Evalfux 4A (Kuraray) |
|
|
IgM, LDL | |
| Evalfux 5A / lipofilter (Kuraray) |
|
|
LDL-C | |
| versapor acrylic copolymer | Cryoglobulin filter (Pall Gelman, Ann Arbor, MI, USA) |
|
|
cryoproteins |
| cellulose diacetate | Plasmaflo-AP06M (Asahi, Tokyo, Japan) |
|
|
cryoproteins |
(plugging is frequent and requires multiple backwashing during the procedures)
(best results at 4°C)
columns removes IgG
pheresis by
and heterozygous who with documented, symptomatic CAD,
hemolytic
anemia,
Staphylococcus
spp. infection and thrombosis at the site of venous access, allergic reactions
leading to anaphylaxis
and activation of coagulation, complement, and fibrinolytic cascades, and
aggregation of platelets. Systemic
arterial hypotension
during plasma exchange is aggravated by the concomitant administration
of ACEI.
During the course of plasma therapy, patients are anticoagulated beacuse
of the loss of platelets and clotting factors removed with plasma. In the
absence of liver dysfunction, clotting factors in the circulation return
to normal within 24 hours.
: sickle cell crises with suspected target organ damage or before major
surgery
: sickle cell crises with priapism
(side effects : thrombocytopenia, protamine-induced systemic
arterial hypotension)
(high costs),
possibly through reduction in high concentrations of these toxins. Although
MARS has been shown to be useful in FHF, its clinical efficacy in subfulminant
hepatic failure and less severe forms of acute liver failure (ALF) remains
uncertain. The current literature also suggests that it may be beneficial
to treat cases of acute-on-chronic liver failure (AoCLF)
(subclavian catheter or internal jugular catheter), which has direct access
to the heart. Using these access sometimes tend to have problems like blocked
catheter from clots or infection at the insertion site. Therefore, extra
care has to be taken with temporary access.
and cephalic vein
at the wrist. Patency = 90% after 1 year, 75% after 4 years
and the cephalic vein,
with patency = 70% after 2 years
and the basilic vein,
with patency = 70% after 2 years
and femoral vein.
and the saphenous vein),
but are of second choice due to higher incidence of thrombosis, infections
and reduced depurative efficiency
– antidecubital vein
– femoral vein
or greater saphenous vein
or the Dialock system for pediatric patients
or concomitant sepsis)
into and removed from the peritoneal cavity as either a continuous (2 L
/ 4 hr) or an intermittent procedure. It has effectiveness similar to hemofiltration.
The dialyzing hyperosmotic solution (Dianeal (PD-2)) contains:,
expecially in diabetic patients,
loss of endogenous protein and amino acids, retroperitoneal
fibrosis,
hyperglycemia
and hypertriglyceridemia
(dialyzing hyperosmotic solution often is glucose- or amino acid-rich and
some pass into liver via portal circulation)
has consistently been associated with a reduced mortality rate in kidney
dialysis patients due to the cholesterol-lowering effects of systemic inflammation
and malnutrition, 2 common complications of dialysis. When dialysis patients
don't have inflammation or malnutrition, hypercholesterolemia predicts
a progressively higher risk deathref
=> renal clear cell
carcinoma.
Other transport activities were also observed in these devices and included
active bicarbonate transport, which was decreased with acetazolamide, a
carbonic
anhydrase II
inhibitor, active glucose transport, which was suppressed with phlorizin,
a specific inhibitor of the sodium-dependent
glucose transporters (SGLTs),
and p-aminohippurate (PAH) secretion, which was diminished with
the SLC22A6 / anion transporter
inhibitor probenecid. A variety of differentiated metabolic functions was
also demonstrated in the RAD. Intraluminal glutathione breakdown and its
constituent amino acid uptake were suppressed with the irreversible inhibitor
of g-glutamyl transpeptidase acivicin; ammonia
production was present and incremented with declines in perfusion pH. Finally,
endocrinological activity with conversion of 25-hydroxy(OH)-vitamin D3
to 1,25-(OH)2 vitD3 was demonstrated in the RAD.
This conversion activity was up-regulated with parathyroid hormone and
down-regulated with increasing inorganic phosphate levels, which are well-defined
physiological regulators of this process in vivoref.
It demonstrates metabolic, immunologic and endocrine activity with systemic
effects in patients with acute
renal failure (ARF)
and multiorgan failure (MOF)ref1,
ref2,
ref3
: it ameliorates cardiac and vascular dysfunction, alters systemic cytokine
abnormalities, and improves survival time in a large animal model of Gram-negative
septic shockref1,
ref2,
ref3.
Hemodialysis and hemofiltration have been important technologies in saving
the lives of patients with ARF and CRF by clearing small solutes from plasma
and thereby preventing death from acidemia, hyperkalemia, volume overload,
and uremia. These therapeutic approaches, however, are still suboptimal,
as patients with ARF have mortality rates exceeding 50%, and patients with
end-stage
renal diseases (ESRD)
have, on average, a life expectancy of 4-5 years. The preeminent cause
of death in patients with ARF is the development of sepsis or the systemic
inflammatory response syndrome with resulting systemic vasodilation, hypotension,
ischemic injury to solid organs, multi-organ failure, and death. This vasodilation
is due to persistent and excessive pro-inflammation. Similarly, the reduced
survival times of patients with ESRD on chronic dialysis have been associated
with a persistent and chronic systemic pro-inflammatory state. The loss
of renal tubule cell mass acutely in acute tubule necrosis and chronically
in ESRD results in an immunologically dysregulated state leading to excessive
pro-inflammationref1,
ref2.
sandwiched between artificial plates or capillaries. The problem is deciding
which liver functions are the most important and shouyld be carried out
by the BAL bioreactor. Biosynthetic capacity is perhaps the least essential
because most proteins synthetised by the liver can be given exogenously
to patients. The generation and detoxification of ammonia is undoubtedly
important. Although an increase in ammonia in the blood is toxic to the
CNS, reduction of ammonia levels per se is not sufficient to alleviate
this toxicity. The enormous scale-up required to use BAL devices clinically
is problematic : at least 1010 hepatocytes in a BAL bioreactor
would be needed to support a patient's failing liver. Sinusoidal endothelial
cells can be expanded to achieve that number. A good vitality of hepatocytes
is maintained for 2-3 weeks, but functions decrease. Encapsulation of hepatocytes
with calcium or sodim alginate gel could reduce immunogenicity and reduce
immune-mediated cytolysis. Freezing and thawing and hepatocytes could store
the material for long times. Modular extracorporeal liver support (MELS)
systems combine biologic liver support with artificial detoxification
technologyref.
),
could potentially provide and alternative source of human hepatocytes.
Although the differentiation of bone marrow derived stem cells into hepatocytes
has been demonstrated in vivo, it has not been achieved in vitro as yet.
However, liver-derived hamatopoietic cells can give rise to cells that
resemble bile duct epithelial cells. Embryonic stem (ES) cells offer
another valuable option, particularly as human ES cell lines are now available.
in the treatment of infertilityref
to induce hypogonadotropic hypogonadism 2 weeks before ovarian stimulation| GnRH analogue (GnRHa) |
|
|
|
|
| GnRH agonist | ||||
| nonapeptides | ||||
| leuprorelin | S.C. | 500-1000 mg/d | ? | yes |
| I.M. depot | 3.75-7.5 mg/mo | ? | yes | |
| buserelin | S.C. | 100-500 mg/d |
|
|
| I.N. | 300-400, 3-4 times daily | yes | ||
| goserelin | S.C. implant | 3.6 mg/mo | ? | seldom |
| histrelin | S.C. | 100 mg/d | ? | no |
| decapeptides | ||||
| nafarelin | I.N. | 200-400 mg 2/d | ? | yes |
| triptorelin | S.C. | 100-500 mg/d | 50 mg/d | yes |
| I.M. depot | 3.75 mg/mo | ? | no | |
| GnRH antagonist | ||||
| cetrotide | S.C. | single dose | 2 mg/injection | yes |
| S.C. | multiple dose | 0.25 mg/d | yes | |
| orgalutran | S.C. | multiple dose | 0.25 mg/d | yes |
-induced
ovulation
may be responsible : melatonin levels naturally cycle in response to light
and dark. Until recently it was thought that melatonin acted only through
the pituitary gland in the brain (this gland is "switched off" during IVF
treatment because it controls a woman's own hormone production, preventing
any activity which could interfere with treatment which artificially stimulates
the ovaries to release an egg), but there are also melatonin receptors
throughout the reproductive system : the hormone may act directly on reproductive
tissues to make women more fertile in lighter months. If you look at the
animal world, it's biologically better for offspring to be born in spring,
so they then get 6-8 months winter comes to develop : the same pattern
had historically been seen in natural human reproduction, but it was less
obvious now because people had more control over deciding when they tried
for a baby, and could use contraception to prevent conception. It has been
observed that there is a seasonal variation, but it has been thought it
might be linked to warmer temperatures in summer months.
monitoring of follicular growth (size and number) : eventually endocrine
monitoring of [17b-estradiol]plasma-assisted
pick-up under general or local anesthesia and 36 hrs after administration
of hCG : on average, of 100 oocytes prelevated (within 10-30'), 90 are
mature and can be surgelated (egg
cryopreservation). Doctors are still figuring out how to do this reliably
without the formation of damaging ice crystals within the eggs, and there
have been fewer than 100 live births using this method. 40 survive treatment
but 4 are damaged. At least 2 US companies, however, already offer women
the chance to freeze their oocytes. Of the remaining 36 eggs, 17 are fertilized
(due to high H2O content the cell membrane becomes stiffer and
fertilization has to be accomplished by microinjection) and only 2 undergo
a correct implantation giving start to normal pregnancies. On average,
3.5 pregnancies are obtained every 100 oocytes prelevated. The average
likelihood of becoming pregnant after one IVF attempt is roughly 20-30%,
and this drops off with age. Doctors have been searching for a way to distinguish
eggs with a high chance of IVF success based on the their shape, genes
or metabolism, but long telomeres could be the secret of success : eggs
with an average telomere length shorter than around 6,300 DNA units never
produce a pregnancy
patient about to undergo chemotherapy and froze it at -196° C. 6 years
later, they thawed 15 fingernail-long strips and grafted them under the
woman's abdominal skin using a local anaesthetic (they feel like beads
under the skin) : transplanting the ovarian tissue back into the patients
is also difficult and there is the danger that the tissue may contain cancerous
cells, but putting the transplant beneath the skin of the abdomen reduces
the health risks and it can be easily removed if necessary. 3 months later,
the woman's hormones prompted the tissue to start making eggs, which the
doctors boosted with fertility drugs. Over 8 months they collected 20 mature
eggs with a needle and mixed 8 of them with sperm for IVF : 2 eggs went
on to form embryos in culture. One was implanted in the woman, but it did
not lead to pregnancyref.
This is not surprising in IVF treatment, where the chances of successful
implantation are 20-30% at best : Oktay is trying once more to produce
a pregnancy in the same woman and he is about to start the procedure on
others. Once the technique is improved, doctors say it may offer hope to
cancer patients or others whose ovaries are affected by disease or drugs.
Some of these patients have already banked their ovarian tissue. In 1997,
the Belgian woman Ouarda Touirat was diagnosed with stage IV Hodgkin's
lymphoma
- cancer of the lymph system that had spread to other organs. 5 tissue
samples, about 12-15 mm (0.5-0.6 of an inch) long and 5 mm (0.2 of an inch)
wide, were taken from her left ovary. 4 of the samples were cut into 70
small cubes while the other was left uncut; all were frozen in liquid nitrogen
at -196 C (-320 F). Touirat then underwent a powerful course of seven anti-cancer
drugs over six months which caused her periods to end, and this was followed
by a course of radiotherapy. Tests confirmed that both her ovaries had
failed. In 2003, after her recovery from cancer, the stored tissue was
thawed and reimplanted in the pelvic region, tucked into a niche next to
the right ovary, which like the remains of the left ovary had atrophied.
A week later, a network of tiny blood vessels could be seen around the
implanted tissue, a good sign that it had been accepted. 5 months later,
the patient started to resume her menstrual cycle and after 11 months she
conceived. She became pregnant by natural means, not by IVF. They observed
a developing egg in the graft, but none in the two ovaries, just before
the woman fell pregnant. On Sep 23, 2004 at the Cliniques Universitaires
Saint-Luc in Brussels, > 7 years after slices of ovary were placed in storage
to give her the chance of motherhood after cancer therapy, 32-year-old
Touirat gave birth to a healthy 3.72-kg (8.2-pound) girl named Tamararef.
Oktay believes the pregnancy could have resulted if one of the woman's
ovaries survived the chemotherapy and produced eggs on its own : few women
who have chemotherapy for Hodgkin's lymphoma, as this woman did, are completely
sterilised by the treatment
in which tumour cells might be reintroduced with the graft and any children
born from the technique might be somehow different, although animal experiments
suggest that offspring should be normal. Over the last few years, Oktay's
group have grafted pieces of thawed ovarian tissue on to women's ovaries
or arms, and showed that the tissue resumes making eggs and live embryos.
increases if a woman has had IVF. And the risk is even greater if
the eggs come from a non-relative. 61 pregnancies resulted from egg donation
were compared with a control group of standard IVF pregnancies, in which
the eggs come from the woman who wants to get pregnant. Hypertension attributable
to the pregnancy struck 12.5% of women in the first group, as opposed to
3.7% of those who had the more common procedure. But the researchers discovered
another striking difference in the group receiving donated eggs: the risk
of high blood pressure increased by more than fivefold in cases where a
woman had received an egg from a unrelated person, but only twofold when
the egg came from a sibling. The researchers have yet to prove why eggs
from unrelated donors make complications more likely, but they believe
the answer lies in how the immune system reacts to the developing fetus.
The presence of foreign proteins on these eggs could trigger an abnormal
response in the patient's immune system leading to hypertension. The immune
system could be to blame. Some people believe an immune response against
cells in the uterus might lead to the release of reactive oxygen molecules
in the blood, which could damage the blood vessel cells that protect against
hypertension. But there is still much debate over the issue. Their findings
should encourage sisters to consider donating eggs. Donation from a sibling
would improve the outcome both in terms of the well-being of the pregnant
mother and the health of the baby
,
which are able to give rise to almost every tissue in the body, would be
removed and nurtured in the lab with molecules that encourage them to develop
into either sperm or eggs. The resulting cells could be fused with the
sperm or egg of the other partner by fertilization, and the embryo could
then be implanted. Such a technique would do away with a lot of the objections
to reproductive cloning infertile couples with defective eggs or sperm
for whom current ARTs do not work.-assisted
direct insemination of a preovulatory follicle in women with at least one
patent fallopian tube and controlled ovarian stimulation.-assisted
pick-up and then placed, together with a sample of semen, in a transcervically
catheterised uterie tube
by mechanical or local application of a zona solvent like acid or
enzymes using microneedle to inject the material
of early cleaved embryo by partial slicing by means of micromanipulation
before replacement so as to improve chances of eventual
hatching
to provide an access through which sperm can more easily gain path to the
egg
: zygote intra-Fallopian
transfer (ZIFT) : echographic pick-up + IVF+
laparoscopic delayed transfer of a maximum of 3 zygotes in the fimbrial
end of one healthy fallopian tube => natural tubal transport of embryos
to the uterus. Better nidation rates than gamete
intra-Fallopian transfer (GIFT).-assisted
pick-up; after IVF the zygote
is then placed in a transcervically catheterised uterine tube
: fertilization
in
vitro and embryo transfer (FIVET / IVF-ET)
: nidation occurs in 15-20%. Despite both doctors and patients widely believe
that placing several embryos into the womb during treatment boosts the
chances of pregnancy, the pregnancy rate after transferring 1 embryo is
just as high as that after transferring 2. In January 2003, Swedish health
authorities banned the transfer or > 1 embryo at a time except in exceptional
circumstances : the rate of pregnancies after the legislation was just
as high as it was before (around 33% were successful). However, the frequency
of twin pregnancies fell from 23% to < 6% (transferring a single embryo
can still result in twins if 1 embryo splits naturally into 2). 2 studies
from US fertility clinics mirrored the Swedish results. When otherwise
healthy women were offered the choice of having one embryo implanted instead
of 2, pregnancy rates remained just as high (over 70%). Researchers hope
that the data, which echo that emerging from a number of other studies,
will encourage more clinics to favour single embryo transfers. In women
under 36 years of age, transferring one fresh embryo and then, if needed,
1 frozen-and-thawed embryo dramatically reduces the rate of multiple births
while achieving a rate of live births that is not substantially lower than
the rate that is achievable with a double-embryo transferref.
In women aged > 37 years, or with previous experience of failed IVF, however,
it may still make sense to transfer more than one embryo. The risk of multiple
births is much lower in these groups. Many countries other than Sweden
are already encouraging a limit to the number of embryos transferred. In
September 2004, the ASRM released new guidelines advising USA clinics to
transfer < 2 embryos to women < 35. However, one of the biggest obstacles
to the widespread adoption of single embryo transfer is that patients in
the USA and many other countries pay for their own treatment, which often
costs over $10,000 for a single IVF cycle. Wanting to maximize their chances
of success, patients tend to favour the transfer of multiple embryos in
each cycle; and clinics support the practice because they believe it will
increase the pregnancy rates, which they publish to attract patients. To
overcome this perception, there is a need to educate patients about the
new data and about the health risks associated with twins
(sHLA-G) (secreted by embryos and thought to help them survive after
implantation) in supernatants of individually cultured 46-h embryos is
a potentially valuable indicator of 'embryo competency' and IVF outcome.
Of women aged under 39 whose embryos pumped out above-average levels of
HLA-G, 71% became pregnant. Of women whose embryos made below-average amounts
of HLA-G, only 22% fell pregnant. The pregnancy rate for women over 39
was lower overall, but high HLA-G embryos still fared betterref.
Anyway one criticism is that although the team measured HLA-G produced
by each embryo, they implanted 2-3 embryos into the uterus at a time, so
they cannot prove that the high HLA-G embryos were the ones that implanted.
Earlier studies have hinted that embryos making HLA-G divide faster and
are better able to implant. By selecting specific embryos for transfer
based on their individual sHLA-G expression, pregnancy and implantation
rates can be maximized while the number of embryos transferred can be reduced,
thereby minimizing the incidence of high-order multiple pregnancies
to be carried out at the University College Hospital in London. Up to 4
couples will be approved
to be carried out at the University College Hospital in London. 4 couples
were be approved, including Angela Donovan. Women already are allowed to
screen for retinoblastoma 11 weeks into pregnancy and abort affected foetusesref
: hematopoietic
stem cells (HSC) transplantation
from umbilical cord blood or bone marrow from the newborn will be used
to treat disease in an older brother or sister.,
the first child in Britain, and among only 5 in the world, to receive a
successful transplant from a sibling born to help cure their illness. His
parents, Michelle and Jayson, received initial treatment, including IVF,
from the Assisted Reproduction and Gynaecology Centre, in London. But a
ruling by Britain's Human Fertilisation and Embryology Authority (HFEA)
forbiddiong PGD meant the couple were forced to turn to a clinic in Chicago
to complete the procedure. In 2002, two 3-day-old embryos were implanted
in Mrs Whitaker. In June 2003, she gave birth to Jamie, a perfect genetic
match for his brother. It meant stem cells from the baby's umbilical cord
could be used to treat Charlie. The transplant was practiced in July 2004
at Sheffield Children's Hospital and in October tests on Charlie's bone
marrow have produced very promising results..
The perfect match Jodie Fletcher born on August 2005,
the disease that affects their 5-years old son Zain Hashmi. However,
the Hashmis have not yet conceived such a child, and currently face a second
legal challenge to the HFEA's decision, by the pro-life group Comment on
Reproductive Ethics (CORE). The family hoped that umbilical cord blood
would cure Zain, who needs painful blood transfusions every 3-4 weeks and
drugs from a drip for 12 hours, 5 nights a week. After 6 attempts and several
miscarriages the couple have yet to have a baby. With time running out
for Mrs Hasmi, 40, they believe their best chance lies in a donor. The
UK's highest court gave the go ahead for the creation of "saviour siblings"
to give umbilical cord, blood, or bone marrow to try to save the life of
a brother or sister. 5 judges in the House of Lords unanimously ruled that
the law that set up the HEFA gives the authority the power to licence,
alone or separately, both PGD and tissue typing on embryos used in treatment
for IVF. The ruling, upholding an appeal court judgment in April 2003,
removes all doubt for Raj and Shahana Hashmi, who have been trying to produce
a sibling with the same tissue type as their son Zain, aged 6, who was
born with thalassaemia major. The couple, from Leeds, have so far
had 6 unsuccessful attempts at IVF, but each time they either failed to
produce an embryo of the right tissue type or the pregnancy ended in a
miscarriage. The case was taken to the House of Lords by Josephine Quintavalle
and her campaigning group, Comment on Reproductive Ethics (CORE), who argued
that the HEFA had no power to licence the creation of a baby to save the
life of another. The arguments hinged on the wording of the Human Fertilisation
and Embryology Act 1990. Lawyers for Mrs Quintavalle, who had won her case
in the high court before the judge's ruling was overturned by the appeal
courtref,
argued in the House of Lords that the act's wording allowed the authority
to licence preimplantation genetic diagnosis but not tissue typing. But
the law lords decided that the authority's discretion was wide enough even
to allow the selection of an embryo's characteristics on social grounds,
although it was unlikely that such a licence would be granted. Lord Hoffmann
said that the technique of taking a single cell from an embryo and testing
it for genetic disorders and tissue compatibility was "a way to save the
Hashmi family from having to play dice with conception. He noted that parliament
had said nothing about, for example, sex selection. The only reasonable
inference is that parliament intended to leave the matter to the authority
to decideref
if the fetal Rh blood type is positive. Although the incidence of severe
RhD alloimmunization has decreased with prophylactic anti-D immunoglobulin
administration during and after pregnancy, sensitization still occurs in
a small group of women. In such women, Rh disease will continue to be significant
problem and for their babies who may be affected. Preimplantation genetic
diagnosis (PGD) may be utilized to avoid materno-fetal blood group incompatibility
in an RhD-sensitized woman. Biopsy of a single cell from early cleavage-stage
embryos screening for RhD-negative embryos allows the transfer of only
RhD-negative embryo(s) into the uterus. This avoids any complications related
to haemolytic disease of the fetus and newborn. This article describes
the first reported case of an unaffected pregnancy using PGD for Rh disease.
IVF and embryo transfer resulted in a clinical pregnancy and the birth
of a healthy girl in November 2003, confirmed to be blood type RhD negative,
to a couple who had previously had one child severely affected by Rh disease.
PGD in couples with a heterozygous RhD-positive male partner provides an
option for avoiding haemolytic disease of the newborn in RhD alloimmunized
mothersref
used to detect chromosome copy number, the greatest inherent risk of misdiagnosis
is due to chromosomal mosaicism--ie, the co-existence of aneuploid and
diploid cells in one embryo. This situation has been shown to affect, on
average, at least 50% of cleavage-stage embryos in numerous studies worldwide
that used FISH, molecular analysis (comparative genomic hybridisation),
and karyotyping. For single-gene and chromosomal cases, the easiest way
to increase accuracy is to analyse 2 independent cells : an acceptable
pregnancy rate (15% versus 27%) can still be achieved despite a policy
of taking 2 cells from embryos consisting of at least 6 cells
than conventional IVF patients
due to simultaneous transfer of 3-4 embryos in FIVET
(20-30% vs. 1%) The rate of multiple gestations after in vitro fertilization
is 26.4% in Europeref
and 35.3% in the USAref,
as compared with 1.1% after natural conception. Adverse outcomes associated
with high-order gestations include serious perinatal morbidity and mortality
and long-term disabilities (Crowther CA. Multiple pregnancies. In: James
DK, Steer PJ, Weiner CP, Gonik B, eds. High risk pregnancy: management
options. 2nd ed. Philadelphia: W.B. Saunders, 2002:129-52)
stage would enhance the likelihood of pregnancy as compared with the usual
procedure in which the embryo is transferred at the single-cleavage stage
(day 3)ref1,
ref2,
but this suggestion remains controversialref.
The main disadvantage of transferring the embryo at the cleavage stage
rather than at the blastocyst stage is that the morphologic criteria that
govern embryo selection on day 3 are highly subjectiveref
and less accurately reflect the genetic quality (euploidy status) of embryos
than do the criteria used on day 5. For example, among women 36 years of
age or older, 59% of embryos judged as "top quality" on day 3 were found
to be aneuploid, as compared with 35% of blastocysts judged as "top quality"
on day 5ref1,
ref2.
If these findings also apply to women under 36 years of age (albeit in
a lower proportion)ref,
then selecting only one cleavage-stage embryo for use (even if it is of
top quality) would increase the chances of transferring a chromosomally
abnormal embryo. On the other hand, a potential downside to the use of
blastocyst-stage embryos is that some embryos are not able to reach the
blastocyst stage in cultureref.
Additional concerns about the use of blastocysts include the possibilities
of an increased risk of monozygotic twins, an altered sex ratio of births,
and epigenetic effects on the embryo. In infertile women under 36 years
of age, those undergoing transfer of a single blastocyst-stage (day 5)
embryo embryo have a higher rate of pregnancy than those undergoing transfer
of a single cleavage-stage (day 3) embryo (P=0.02) . The rate of delivery
was also significantly higher in this group than in the group undergoing
transfer of a single cleavage-stage embryo (32.0% vs. 21.6%; relative risk,
1.48; 95% confidence interval, 1.04 to 2.11). 2 multiple births occurred,
both of monozygotic twins, both of which were in the group undergoing transfer
of a single cleavage-stage embryoref.
Despite the well-recognized risks associated with multiple gestations,
many patients still want to have multiple embryos transferred to enhance
the probability of pregnancyref.
Increasing awareness of the costs and risks of multiple births has led
the medical community to reduce the number of embryos transferred. For
single-embryo transfer to be accepted by patients, doctors, and payors,
however, it must be associated with acceptable pregnancy rates. One approach
to optimizing pregnancy rates after single-embryo transfer is to follow
it with transfer of a frozen–thawed embryo in cases in which the initial
transfer is not successful. In a previous randomized trial, this strategy
achieved a rate of live births that was not substantially lower than the
rate after transfer of two fresh cleavage-stage (day 2) embryos (38.8%
vs. 42.9%) and was associated with a dramatic reduction in the rate of
multiple births (0.8% vs. 33.1%)ref.
However, these results were obtained among women under 36 years of age
who had at least two good embryos available for transfer and thus had a
good prognosis, and the plausible difference in rates of live births between
the two protocols (on the basis of the 95% confidence interval) was as
high as 11.6%. For some couples, this difference may not be acceptable,
particularly given the observation that the stress associated with in vitro
fertilization leads many couples to abandon treatment without proceeding
to a second trial, even if they can afford itref.
Increasing the pregnancy rate in the cycle in which fresh embryos are used
would be expected to increase the acceptability of single-embryo transferref.
The rate of live births after transfer of a single fresh blastocyst-stage
embryo was similar to that after transfer of two fresh cleavage-stage (day
2) embryos in the Scandinavian studyref.24
Smaller studiesref1,
ref2
have found rates of ongoing pregnancy of up to 60% after elective transfer
of a single blastocyst. Similarly, analysis of a population-based sample
of 50,819 in vitro fertilization procedures in the USA in 2001 revealed
that transfer of a single blastocyst-stage embryo resulted in a live-birth
rate ranging from 31.6 to 39.5% among women 20 through 37 years of ageref.
The success of single-blastocyst transfer will require effective methods
of cryopreservation of blastocysts. Data are needed to compare the rates
of live births (including both births resulting from transfer of fresh
embryos and those resulting from transfer of frozen–thawed embryos) after
transfer of cleavage-stage and blastocyst-stage embryos. A live-birth rate
of 11% has been reported after transfer of frozen–thawed blastocyst-stage
embryos (94 of 857 cycles)ref,
whereas the live-birth rate after transfer of freeze–thawed cleavage-stage
embryos is approximately 15%. A concern in randomly assigning patients
to treatment at the time of consultation, before embryologic data were
available, was that it might lead to a high rate of cancellation of transfers
of blastocyst-stage embryos. However, among this population of women under
36 years of age who were undergoing a first or second trial of in vitro
fertilization, cancellation of transfer on day 5 was rare. Prospective
studies are needed to determine whether blastocyst transfer is appropriate
in older women or in women with repeated implantation failures. Recent
dataref1,
ref2,
however, suggest that the number of embryos with two pronuclei (day 1)
or cleavage-stage embryos may serve as a predictor of the success of blastocyst
transfer. An increased risk of monozygotic twins has previously been reported
with blastocyst transfer in retrospective studiesref1,
ref2.32,33
There were no cases of monozygotic twins after single-blastocyst transfer
in our study, but the study was not powered to assess the risk of monozygotic
twins or other potential risks associated with extension of embryo culture
to day 5, such as birth defects and long-term health outcomes. The 2 second-trimester
pregnancy losses in the blastocyst-transfer group, including the elective
termination owing to anencephaly, may be a cause of concern, although the
rates of such complications did not differ significantly between the groups.
Larger studies are required to address these issues. The higher rates of
ongoing pregnancy and delivery after transfer of a single blastocyst-stage
embryo than of a single cleavage-stage embryo are probably due to a better
selection processref.
Although some genetically abnormal embryos are able to reach the blastocyst
stage, the risk of aneuploidy in a top-quality blastocyst is lower than
that in a top-quality cleavage-stage embryoref1,
ref2.
A recent meta-analysis comparing transfer of cleavage-stage and blastocyst-stage
embryos did not show a difference in favor of the latter embryosref.
However, this analysis included studies involving transfer of more cleavage-stage
embryos than blastocyst-stage embryos, and the transfer of more cleavage-stage
embryos could have compensated for the potentially lower quality of any
individual cleavage-stage embryo relative to that of a blastocyst-stage
embryo. In appropriately selected patients (with > 3 good embryos on day
3), transfer of 2 blastocysts results in a significantly higher delivery
rate than transfer of two cleavage-stage embryos, but with the drawback
that almost half of the initial pregnancies involved twinsref
(<37 weeks, 30.3 vs 6.3%) : compared with spontaneously conceived twins
who were matched for maternal age, IVF twins have an increased risk of
preterm birth between 32 and 36 weeks of gestation (OR = 1.48), and an
elevated risk of preterm birth at <37 weeks of gestation when parity
is also matched for an OR =1.57. There was an increased rate of cesarean
delivery among IVF twins (OR = 1.33). There were no significant differences
in incidences of perinatal death, low birth weight infants, or congenital
malformationsref.
(<2500 g, 27.4 vs 4.6%)
(5.4% of all babies in the IVF group (1.39 [1.25-1.54]), and the rates
of neural-tube
defects (NTDs)
and oesophageal
atresia
were higher than those in the controls
in the IVF groupref1,
ref2
(1.7), epilepsy
(1.5), congenital
malformations
(1.8) or childhood cancer
(1.6), but also for asthma
(1.4) or any infection
(1.4).,
Angelman
syndrome
and retinoblastoma
are injected into an animal inducing a myeloma and mAbs are recovered from
serum after sacrifice. In such a model it isn't possible to obtains MAbs
against intracellular Ags. sometimes when they are injected into a species
different from that of the animal above mentioned, they can become target
for host Abs (e.g. human anti-mouse activity (HAMA)).
(unproved yet; it could have higher effectiveness)
)
:
).
He aims to produce cloned ES cells using the DNA of adults with a genetic
form of MND and then coax these to develop into motor neurons -- the long
nerve cells that transmit messages from the brain and spinal cord to the
muscles. The eggs they use will not be allowed to grow beyond 14 days.
Once the stem cells are removed for cell culture, the remaining cells will
be destroyed. They will compare the behaviour and chemical profile of neurones
with the gene defect to those without
in sheep's milk which can be used in medicines to treat cystic fibrosis
and emphysema. But the work was put on hold after its partner Bayer pulled
the plug on the trials, saying they were too costly. PPL said on July 15,2003
it was to slaughter up to 3000 genetically modified sheep at its 2 farms
in Scotland, but had not confirmed how many of the Whakamaru flock, made
up of about 3000 genetically modified sheep and 1000 normal sheep, will
be killed.
animals, such as the Tasmanian tiger (Thylacinus
cynocephalus), an Australian marsupial, may prove more difficult,
but cells frozen under modern conditions might offer a way to preserve
animals that have more recently become endangered. Resurrecting a species
will require more than recreating 1-2 animals. Genetic diversity, having
many animals to interbreed, is essential for maintaining a healthy population.
Alliance
to Rescue Civilization (ARC) wants to establish a genetic Noah's Ark
of sorts or a protected stash of genomes from Earth's wide array of species
and individuals. The concept is somewhat similar to the Frozen Zoo project,
based at the San Diego Zoo. The difference is this genetic library could
one day be used to revive the human species. And it's not just the ARC
that has pondered such a moon-based bank. Bernard Foing, chief scientist
with the ESA, said it's an idea that his agency has discussed for some
time : such a plan is probably decades away and much needs to happen before
any such project becomes even remotely possible. Still, every journey and
project begins with a single step, and that is where the Smart-1 orbiter
comes into play.
)
was cloned by Professor Ian Wilmut of the Roslin
Institute, Edimburgh, in collaboration with PPL
Therapeutics by fusing a mature cell from the mammary gland of a nameless
6-year-old died 3 years before and an egg cell whose nucleus had been removed.
From 277 attempts, just 29 blastocysts implanted in the uterus and she
was the sole living birthref.
The achievement is announced on February 23, 1997. A mammalian oocyte is
a huge cell containing perhaps 100,000 mitochondria. The mature mammary-gland
cell that was merged with the oocyte was much smaller, containing between
2,000 and 5,000 mitochondria. The researchers
could find no mitochondria in cloned sheep that could have been derived
from the mature cell (all came from the oocyte) : as in conventional sexual
reproduction although the recipient oocyte has lost its nucleus, it still
retains the capacity to wipe out invading mitochondria. In 1998, some researchers
suggested that her DNA could have come from an adult stem cell or from
a fetal cell - Dolly's mother was pregnant when the cell for the clone
was taken. But DNA fingerprinting of frozen tissue cleared the argument
up, and re-affirmed Dolly's status as a clone.
and the first and the only named rat clone, is now father to a litter of
healthy 2-month-old pupsref.
Genetically modified rats can be produced by other methods, but their DNA
is altered at random. Cloning gives added control - specific genes in the
donor cell can be altered, added, or removed : genetically modified, cloned
rats take longer to make and suffer more ill health. Small rodents have
been used in medical research for over a century. Mice gained popularity
during the 1980s when researchers developed the ability to manipulate the
mouse genome at will - resulting in some 5000 GM strains.
,
was made by scientists at Texas A&M University. It is a genetic copy
of his donor (skin cells were used), a south Texas buck considered a huge
trophy
.
Researchers sucked several nuclei out of developing fly embryos, and injected
them into a fertilized fly egg. From over 800 initial attempts, they conjured
5 adult insects. But embryonic cells are much easier to reprogramme than
adult cells and there are not many close parallels to what's going on in
mammalsref
)
ambles on to the world stage today. His birth was a feat of ingenuity and
perseverance, but some scientists question the value of the exercise. The
Afghan hound puppy has been hidden from the world at the Seoul National
University in South Korea for the 9 weeks since his birth from a yellow
Labrador retriever. He bears exactly the same DNA as an older hound who
lent a few ear cells to the researchers. He's also quite a survivor, being
the only one of 1,095 cloned embryos implanted in 123 dogs to survive to
healthy puppyhood. Since Dolly the cloned sheep made her appearance nearly
a decade ago, the field has not advanced as much as was expected at first.
Cloning animals has proven difficult and every species presents its own
problems. Even when everything seems to be going right, the majority of
cloned embryos fail because their genes are expressed in abnormal ways.
For dogs, the main challenge lies in harvesting the eggs. Canine eggs leave
the ovary at a very early stage of development and then mature as they
travel towards the uterus in the oviducts. Harvesting the eggs at the point
of ovulation and trying to mature them in a test tube failed. So the research
team had to wait and remove the eggs by flushing them out of the oviducts
using a custom-made solution. The nucleus of each of these egg was removed
and replaced with a nucleus from an ear cell. Successfully fused cells
were then implanted in female dogs. The painstaking work was completed
by the lab of Woo Suk Hwang, the South Korean researcher who is famous
for creating a cloned human embryo and deriving stem cellsref.
It took a team of about 15 people 2.5 years to produce the dog, whose name
'Snuppy' is short for Seoul National University puppy. The donor
dog belongs to a professor of internal veterinary medicine at the university.
The point of bringing Snuppy into the world is to pave the way for a line
of dogs that could model certain human illnesses. But cloning a kennel
of diseased canines is a long way offref.
Future solutions will involve the development of a hormone treatment whichmight
induce canine ovulation, or a method for maturing eggs in a test tube.
Independent evidence from the Seoul National University Investigation Committee
has been provided that Snuppy, the one of the pair to survive, is a genuine
cloneref1,
ref2.)))))))
: they can live to 11 or 12 years and lung infections are common in older
sheep, particularly those housed inside)))
:
gene, which is an important component in breast milk, were born in east
China’s Shandong Province. Only a few countries are capable to do this
type of cloning, including UK and Argentina).
Fused egg cells from hundreds of failed NT attempts in rhesus monkeys all
stopped dividing shortly after the first few divisions. The mitotic spindles
were disarrayed and the chromosomes on the spindles were misaligned. The
daughter cells also contained unequal numbers of chromosomes. The NT oocytes
were missing several proteins essential for proper chromosome distribution
to daughter cells : NuMA1
needed for spindle pole assembly, as well as 2 motor proteins, KIFC1
/ HSET and KIF11
/ Eg5. The absence of these proteins was due to their close association
with the oocyte DNA : when the DNA was removed from the oocytes in preparation
for NT, the proteins were also accidentally removed. Reinserting the 3
missing proteins into the fused oocytes allows cell division to proceed
normally. In some animals, such as cows, the cells get their spindle machinery
from other sources, such as the cell that is being cloned. In other animals,
the spindle and its proteins are not as closely associated with the oocyte
DNAref))ref
: attempts to produce the third generation of cloned bulls were unsuccessfulref
technology..
It can also be used to confer susceptibility to a given drug => genetic
ablation of some cell types in the developed organism..
Because of the dominant nature of the knockdown, embryonic phenotypes could
be directly assessed in embryos completely derived from ES cells by the
tetraploid aggregation methodRef)
and seroprophylaxis
levels by overexpression of a D-galacturonic acid
reductase
in gene dose defects
and seroprophylaxis.
Copyright © 2001-2005 Daniele Focosi.
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