biopsy the lining of the sinuses. This will be done after the completion of all the 
treatments or earlier if we find any evidence of injury from the virus. Prior to the biopsy, 
an anesthetic to numb the feeling in the area will be used. A small area beneath your 
upper lip will be used to enter the sinus. This procedure will be done by an Ear, Nose and 
Throat doctor. This will be done after the completion of all the treatments or earlier if we 
find any evidence of injury from the virus. 
To learn whether the experimental virus can correct cystic fibrosis respiratory 
abnormalities and can treat the abnormalities in the sinuses that are almost universal in 
CF, we will obtain computerized tomographic X-rays of your sinuses. We will also 
measure the voltage across the lining of the nose and sinuses. This involves the insertion 
of a needle into the skin on your arm, and touching the inner surface of the nose or sinus 
with a small rubber tube. The rubber catheter and the needle will be connected to a 
voltmeter. A voltmeter is a recording device and does not deliver any electricity to your 
nose. Two different drugs at very low doses will be perfused onto the lining of the sinus 
for approximately 30 minutes. These drugs are terbutaline (which is used to treat 
asthma), and amiloride (which is used to treat heart and kidney problems). These drugs 
are approved for human use, and at the low concentration used, do not have major side- 
effects. To learn whether the treatment was of benefit, we will also study fluid samples 
taken from the sinuses. 
After application of the virus you will be required to be in respiratory isolation for one 
day. We wish to keep you in isolation so that no one else will be exposed to the virus. 
This means that you will be confined to a hospital room and visitors will be required to 
wear protective masks, gloves, and gowns. 
About 2 tablespoons of blood will be drawn on the day of admission and discharge and 
on days 1, 3, 7, 14, and 21. Additional blood samples will be required with the additional 
six treatments. Pulmonary function tests will be repeated at the end of the study or if 
there is a change in your disease. 
2. FORESEEABLE RISKS AND DISCOMFORTS : 
Risks associated with gene transfer using the altered virus are largely unknown. It is 
possible that the virus could cause an inflammation locally at the site of application in the 
sinus or it could damage the tissue in the sinus. These problems might produce local pain 
or bleeding. There is also the very unlikely possibility of scarring in the nose or sinus. It 
is possible that the virus might reproduce under certain circumstances; this unlikely 
possibility might lead to spread of the virus and symptoms of a "cold". This may include 
nasal congestion, runny nose, sneezing, cough or fever. It is possible that a pneumonia 
could occur, but we think this is very unlikely because we will only apply the altered 
virus to the lining of the sinus. Other symptoms caused by naturally occurring 
adenoviruses include sore throat and red, sore eyes. Adenovirus that occurs naturally has 
been known to cause diarrhea and pneumonia, though these usually are caused by 
different types of adenovirus than that which was prepared for this study. If a lung 
infection did somehow occur, then it might cause a worsening of your symptoms of cystic 
fibrosis. Rare problems caused by adenovirus include an inflammation of the bladder. 
An extremely unlikely possibility is the formation of a new type of virus through 
interaction with other viruses. It is possible that participation in the study could cause 
your immune system to form a response against the altered virus. This could affect your 
response to subsequent treatments with the altered vims. It is also possible that you may 
develop an allergic reaction to the vims. The vims you will be exposed to rarely 
introduces new gene into chromosomes. This makes it exceedingly unlikely that the 
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Recombinant DNA Research, Volume 18 
