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About 1 out of 201 Caucasian people carries at least one of the
fatal defective genes that cause cystic fibrosis, CF, or mucoviscidosis
(in Europe) although carriers don't show any signs of the disease.
Therefore, 10 million2 people carry the defective gene and aren't aware
of it. Consequently, it makes it one of the most common genetic defect
in the United States.
CF is a autosomal recessive gene. That means that it may, but
doesn't always skip generations. In order to get this disease, both
parents must be carriers. If one parent has CF and the other one is not
a carrier than there is a 100% chance that their child will be a
carrier. If one parent has CF and the other is a carrier than the child
has a 50% chance of having CF and a 50% chance of just being a carrier.
If both parents are carriers than their child will have a 25% of having
CF, a 50% chance of being a carrier and a 25% chance of not being
affected. CF is common in both males and females, there is not a
specific sex that it is more common in.
How does a person know if they have CF? There are many symptoms to
this deadly disease including: salty tasting skin, constant coughing,
large amounts of mucus, trouble gaining weight, frequent greasy, foul
smelling bowel, growths in the nose (nasal polyps) and clubbed or
enlarged fingertips and toe tips is another symptom. Now there are many
tests that can be done to find put if a person has CF.
One way which CF can be detected is to observe the symptoms. A
person doesn't need to have all the symptoms in order to have cystic
fibrosis, but they usually show most of them. Another way are different
genetic testing. Doctors can now do genetic testing for CF, but about
10 years ago they couldn't. In 1989, the location where the of the
defective gene on chromosome number 7 is was discovered by Francis S.
Collins from University of Michigan. Tests can now be taken to see if
an unborn child is infected with CF such tests are amniocentesis,
chronic villus biopsy3 and a removal of cells from the embryo during
invitro.
Many years ago, New York4 had a heat wave, and the hospitals became
overwhelmed with dehydrated CF children. These children became
dehydrated much quicker than children without the disorder. Thus
eventually resulting in the formation of the sweat test which is now
the standard test. Doctors place a pad or filter paper on a patients
arm or back. A chemical called Pilocarpine, makes a burst of
electricity to produce more sweat. Then the pad is wrapped in plastic
and is sent to a lab to get analyzed. The doctors then would look for a
high chloride content in the sweat. Another test is a blood test that
is administered 3 days after a baby is born. It is called
Immunoreactive Trypsinogen5 if that comes back positive it is then
double checked with a sweat test.
Furthermore CF causes the sweat glands to release about 5 times6 as
much salt as a normal person would. This is why the skin of a CF
patients may taste salty. They don't sweat more, but when they perspire
more salt is excreted. This causes the person to dehydrate.
CF is a disorder that causes the body to produce larger amount of
mucus than normal. In a normal person, mucus in the lungs helps get rid
of germs and bacteria in the air. In a CF patients the lungs become
covered with a sticky mucus that is hard to remove and promotes
infection from bacteria. Over time infections cause the lungs to become
extremely weak, therefore ending in respiratory failure.
Also CF affects the digestive tract. The overproduction of mucus
causes the pancreatic ducts to be clogged. Therefore preventing
necessary enzymes to digest fats and proteins. Without those enzymes CF
patients can't gain weight. The undigested proteins and fats pass right
through the body creating smelly bowel. In some cases this malnutrition
causes people to die when they are only children. Also it is more
common for people with cystic fibrosis to develop digestive tract
cancer7. High levels of the protein CFTR (which the gene makes) are
found in the digestive tissues. Doctors explain this increased risk of
cancer because CF induces change in the digestive tract organs that
causes the cell turnover. Patients with gastrointestinal tract problem
should get examined for such tumors.
Women with CF can have children, but it is not very common. Giving
birth is a vigorous process and puts the mother's health at risk. It
may also be hard for a women to get pregnant though because the mucus
blocks the sperm from entering the uterus the to the fallopian tubes.
About 98% of men with CF are infertile8. Even though sperm are
produced, they can't get to the semen because the vas deferens is
blocked. In some new research, it has been thought that men who are
sterile have a different form of CF that doesn't involve the digestive
system and the lungs.
There are now many drugs that are in the market and many more that
are in development. Treatments mainly depends on what organs are
effected. The first new drug therapy in 30 years was approved by the
Food and Drug Administration in December of 93'. It's a mucus-thinning
drug called Pulmozyme®. Pulmozyme® has reduced the number of
respiratory infections and improved lung function. There is also
postural drainage or thumps. This treatment is when the patient is hit
on the back and chest with cupped hands to loosen the mucus so it can
be coughed up easier. There are many antibiotics that help treat lung
infections. Also medicated vapors are inhaled and open clogged airways.
Since mucus in the intestines causes the food not to get digested,
there are enzyme supplements to help. Those enzymes allow patients to
go back to a normal diet. Due to the high concentration of the enzymes
the end result is deterioration of the pancreas leading to diabetes.
With the supplements CF patients can eat normal food.
There are now many studies that the medicine ibuprofen (Advil,
Motrin IB, Nuprin) prevents serious damage to lungs in children who
have CF. The trials involved 85 patients between the ages of 5 and 39
with FEV1 equal or greater than 60%9. In this study patients that took
ibuprofen had a slower rate of decline of FEV1. Patients that took it
for 4 years consistently had even better results and showed best in
patients under the age of 13. The dose of ibuprofen was selected
between 50 and 100up/mL because the anti-neutrophil effects of
ibuprofen are only attained at these levels. There are some side
effects, including conjunctivitis (unknown reason) and epistaxi (due to
the anti-platelet action in the ibuprofen. Doctors say that it is not
sure if stomach pains are due to the ibuprofen, but to stay on the
medicine and to take antacids with magnesium and aluminum and not those
containing calcium. In 1990 two teams of researchers were able to
correct CF cells in a petri dish10. The next huge step happened in
199311, when the first experimental dose of gene therapy was
administered to a human. These were milestones in finding a cure or a
preventive treatment. They were huge steps because it marked the first
time that scientists were able to test new technology in people with
the disease. Also in October of 93'12 scientists at the University of
Iowa made another big step, they determined that the CF gene treatment
worked! It had repaired the defective CF cells. This too was the first
time that the basic defect was corrected in people with the disease.
Doctors and scientists know that the gene number 7 is the gene that
CF is found upon. They also know that gene's protein product most
likely induces the movement of chloride directly or indirectly. They
named the protein ,cystic fibrosis transmembrane conductance regulator
(CFTR). While scientists and doctors were looking for the gene, they
also discovered that there is an abnormality in the DNA of 70%13 of
cystic fibrosis cases. That abnormality often called AF508 mutation, is
made of the deleting of 3 nucleotides from that gene, that then causes
the protein product to be missing an amino acid named phenylalanine at
position 508. Doctors are now trying to get to this gene mutation and
fix it. Scientists are trying to think of a way to administer healthy
CFTR genes to the patients through gene therapy. If all goes as planed
the DNA injected will help the cells to make the normal CFTR protein
and cystic fibrosis will then be terminated.
Doctors have many "delivery vans" that deliver the good genes.
Doctors transport them in viruses, fat capsules and synthetic
vectors14. They are put in the body through the nose or bronchial
tubes. Nine human gene therapy research studies are in the works as of
now. Six of these nine are using the "delivery vans" to deliver healthy
genes to the lungs or the nose. In one study the patients are given
repeated doses of the CF gene therapy treatment to the lungs. While
other studies gives repeated doses of the gene therapy to the nasal
tissue of the patients. The other studies are using the fat capsules
for delivery, another is making the fat capsule in air form and are
breathed in by the patients. Putting the good genes in AAV
(adeno-associated virus) is another way of getting the genes in the
body. In the last study, are also uses the AAV to get the healthy genes
into the lungs. There are about ninety people with CF who have gone
through some sort of gene therapy. "There is a long way still to go
before we have a cure for cystic fibrosis, but we are moving in the
right direction," says David Porteous of the Medical Research Council's
Human Genetics Units at Edinburgh University. Recently a grant15 has
just been given to a company named Aradigm that might get us closer to
a better delivery vector. Dr. Igor Gonda, Aradigm's Vice President of
research and development says, "By combining gene therapy with the AERx
delivery system, our research could ultimately lead to a
broadly-applicable technology for delivery of genes and olignucleotides
to the respiratory tract. Diseases which might be treated by such
genetic therapies include respiratory infections, lung cancer,
emphysema, asthma and cystic fibrosis."16
Cystic fibrosis is a genetic disorder that affects not only it's
victims, but it's victims family and friends. Thanks to modern medicine
and new techniques, the median survival rate has gone from 8 years old
in 50's to 30 years old in the late 90's17. Unfortunately, all this new
medication and discoveries has come to late for many people. One such
individual is Alex Deford. She died when she was only 8 years old. Her
father, Frank, wrote a book based on her life and their many struggles,
from ignorant doctors who wouldn't believe a dying child about a
collapsed lung and the disease itself. Many times with any genetic
disorder, the parents blame themselves. After all it was their bad
genes that caused it. Actually, when Alex first went into the hospital
to get a sweat test, it came back negative, when in reality it was
positive. That was back in the early 70's though. Now sweat tests have
few oversights.
Cystic fibrosis is a disease that doesn't take any prisoners. All
victims will eventually die from complication due to CF. There are
approximately 30,00018 children and adults that are living with this
disorder. Now that scientists have found the gene in which CF is
located, new medicines and new therapies will hopefully be invented.
Perhaps in the next century, we can say that cystic fibrosis is
completely abolished. Maybe the new medications and therapies won't
have to be as painful as they are now. Why should these individuals
with CF be made to suffer in order to get better. Frank Deford says
about chest physiotherapy and the disease, "Two thousands times I had
to beat my sick child, make her cry and plead...and in the end for
what?"
Bibliography
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"AKL And Cystic Fibrosis." http://www.lookup.com/Homepages/70590/AKL_CF.html
"Aradigm Awarded Grant From National Institutes of Health." http://biz.yahoo.com/prnews/97/03/10/ardm_y0022_1.html
"British Team Close to Cystic Fibrosis Gene Therapy." http://www.yahoo.com/headlines/970304/newsstories/cystic_1.html
"CF Ibuprofen Lab: General Information for Physicians." http://www.cwru.edu/orgs/CFIBUPLAB/physgen.htm
"Cystic Fibrosis." http://darwin.clas.virgina.edu/~rjh9u/cfsciam.html
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Neglia, Joseph P., FitzSimmons, Stacey C., Maisonneuve, Patrick,
Schoni, Martin H., Schoni-Affolter, Franzisca, Corey, Mary, and
Lowenfels, Albert B. "The Risk of Cancer Among Patients with Cystic
Fibrosis." The New England Journal of Medicine 332.8 (1995): 494-499.
"Progress in Cystic Fibrosis Research." http://www.cfforg/progress.htm
Raloff, Janet "Ibuprofen Stalls Advance of Cystic Fibrosis." Science News 147.13 (1995): 197.
Ramsey, Bonnie W. "Management of Pulmonary Disease in Patients with
Cystic Fibrosis." The New England Journal of Medicine 335.3 (1996):
179-189.
Silverstein, Alvin, Virgina Silverstein, and Robert Silverstein. Cystic Fibrosis. Chicago: Franklin Watts, 1994.
"What is CF?" http://www.dal.ca/~distsite/frank/cf-basic.html
"Why Does Someone Get CF?" http://www.dal.ca/~distsite/frank/cf-why.html
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